text	date	keywords	Authors	name	Editors	PubName	AuKeywords	KeywordsPlus	Abstract	ReferenceCount	TimesCited	PubYear	PageCount	DOI	SubjectCategory
Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells. It is widely accepted that T helper type 1 (T(H)1) cytokines such as interferon-gamma(IFN-gamma) antagonize allergic diseases mediated by T(H)2 cytokines. The 'hygiene hypothesis' has also proposed that decreased childhood exposure to pathogen-derived T(H)1 cytokines may underlie the recent increased prevalence of asthma, a T(H)2-mediated disease. We show here that influenza A viral infection, which induces large amounts of intrapulmonary IFN-gamma production, unexpectedly enhanced later allergen-specific asthma and promoted dual allergen-specific T(H)1 and T(H)2 responses. Pulmonary dendritic cells obtained from the lung after viral clearance and resolution of acute inflammation conferred enhanced allergic disease and concurrent T(H)1 and T(H)2 immune responses, and these effects were dependent on IFN-gamma secreted during the acute viral infection. Thus, respiratory viral infection and the acute T(H)1 response can positively regulate T(H)2-dependent allergic pulmonary disease in vivo, at least in part, by altering pulmonary dendritic cell function.. respiratory syncytial virus| eosinophilic airway inflammation| th2 immune-responses| influenza-virus| interferon-gamma| antigen exposure| infection| mice| asthma| sensitization.	MAR-2004	respiratory syncytial virus| eosinophilic airway inflammation| th2 immune-responses| influenza-virus| interferon-gamma| antigen exposure| infection| mice| asthma| sensitization	Dahl, ME; Dabbagh, K; Liggitt, D; Kim, S; Lewis, DB	Viral-induced T helper type 1 responses enhance allergic disease by effects on lung dendritic cells		NATURE IMMUNOLOGY		RESPIRATORY SYNCYTIAL VIRUS; EOSINOPHILIC AIRWAY INFLAMMATION; TH2 IMMUNE-RESPONSES; INFLUENZA-VIRUS; INTERFERON-GAMMA; ANTIGEN EXPOSURE; INFECTION; MICE; ASTHMA; SENSITIZATION	It is widely accepted that T helper type 1 (T(H)1) cytokines such as interferon-gamma(IFN-gamma) antagonize allergic diseases mediated by T(H)2 cytokines. The 'hygiene hypothesis' has also proposed that decreased childhood exposure to pathogen-derived T(H)1 cytokines may underlie the recent increased prevalence of asthma, a T(H)2-mediated disease. We show here that influenza A viral infection, which induces large amounts of intrapulmonary IFN-gamma production, unexpectedly enhanced later allergen-specific asthma and promoted dual allergen-specific T(H)1 and T(H)2 responses. Pulmonary dendritic cells obtained from the lung after viral clearance and resolution of acute inflammation conferred enhanced allergic disease and concurrent T(H)1 and T(H)2 immune responses, and these effects were dependent on IFN-gamma secreted during the acute viral infection. Thus, respiratory viral infection and the acute T(H)1 response can positively regulate T(H)2-dependent allergic pulmonary disease in vivo, at least in part, by altering pulmonary dendritic cell function.	49	152	2004	7	10.1038/ni1041	Immunology
Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. Background: Amb a 1-immunostimulatory phosphorothioate oligonucleotide conjugate (AIC) is a novel immunotherapeutic compound consisting of purified Amb a 1 from short ragweed proteins covalently linked to an immunostimulatory phosphorothioate oligodeoxyribonucleotide. In sensitized animals AIC can stimulate an Amb a 1-specific T(H)1 response and decrease pulmonary reactivity to ragweed challenge. Clinical trials have documented reduced allergic response to AIC in comparison with licensed ragweed extract. Objectives: We sought to determine the in vivo effect,of shortcourse immunotherapy with AIC on eosinophilia and cytokine mRNA expression in the nasal mucosa of ragweed-sensitive patients. Methods: Ragweed-sensitive patients with allergic rhinitis were treated with 6 escalating doses of AIC (0.06-12 mug, n 28) or placebo (n = 29) at weekly intervals immediately before the 2001 ragweed season. Symptom scores and medication use were recorded for the 2001 and 2002 ragweed seasons for all patients. A subset of patients (12 receiving AIC and 7 receiving placebo) consented to have nasal biopsy specimens taken before immunization and before and after the first ragweed season. The preseason and postseason biopsy specimens were taken 24 hours after ragweed allergen challenge and compared with the initial unchallenged biopsy specimen to assess cytokine and inflammatory cell responses by using immunocytochemistry and in situ hybridization. Results: AIC was safe and well tolerated by all patients. There was no difference between the AIC and placebo groups in the number of allergen-induced major basic protein-, IL-4-, IL-5-, or IFN-gamma-positive cells in the mucosa in the first weeksafter AIC immunization. On rechallenge and rebiopsy after the end of the 2001 ragweed season, however, AIC-treated patients had a significantly reduced increase in eosinophils and IL-4 mRNA-positive cells and an increased number of IFN-gamma mRNA-positive cells compared with placebo-treated patients. No difference between treatment groups was observed in symptom scores or medication use during the first ragweed season. During the second ragweed season, however, there was a significant decrease in chest symptoms and a trend toward reduced nasal symptoms in the AIC-treated group. Conclusion: Short-course immunotherapy with AIC can modify the response of nasal mucosa to allergen challenge by increasing T(H)1 cytokine production and decreasing T(H)2 cytokine production and eosinophilia. This modification was not immediate but was observed 4 to 5 months after completion of immunotherapy and seasonal ragweed-pollen exposure. The T-cell subset shift after immunization and seasonal exposure was followed by evidence of clinical efficacy in the second ragweed season without additional AIC immunizations.. amb a 1-immunostimulatory phosphorothioate| oligonucleotide conjugate| immunotherapy| rhinitis| ragweed|grass-pollen immunotherapy| messenger-rna| eosinophils| lymphocytes| expression| asthma| increases| mucosa| dna.	FEB-2004	amb a 1-immunostimulatory phosphorothioate| oligonucleotide conjugate| immunotherapy| rhinitis| ragweed|grass-pollen immunotherapy| messenger-rna| eosinophils| lymphocytes| expression| asthma| increases| mucosa| dna	Tulic, MK; Fiset, PO; Christodoulopoulos, P; Vaillancourt, P; Desrosiers, M; Lavigne, F; Eiden, J; Hamid, Q	Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	amb a 1-immunostimulatory phosphorothioate; oligonucleotide conjugate; immunotherapy; rhinitis; ragweed	GRASS-POLLEN IMMUNOTHERAPY; MESSENGER-RNA; EOSINOPHILS; LYMPHOCYTES; EXPRESSION; ASTHMA; INCREASES; MUCOSA; DNA	Background: Amb a 1-immunostimulatory phosphorothioate oligonucleotide conjugate (AIC) is a novel immunotherapeutic compound consisting of purified Amb a 1 from short ragweed proteins covalently linked to an immunostimulatory phosphorothioate oligodeoxyribonucleotide. In sensitized animals AIC can stimulate an Amb a 1-specific T(H)1 response and decrease pulmonary reactivity to ragweed challenge. Clinical trials have documented reduced allergic response to AIC in comparison with licensed ragweed extract. Objectives: We sought to determine the in vivo effect,of shortcourse immunotherapy with AIC on eosinophilia and cytokine mRNA expression in the nasal mucosa of ragweed-sensitive patients. Methods: Ragweed-sensitive patients with allergic rhinitis were treated with 6 escalating doses of AIC (0.06-12 mug, n 28) or placebo (n = 29) at weekly intervals immediately before the 2001 ragweed season. Symptom scores and medication use were recorded for the 2001 and 2002 ragweed seasons for all patients. A subset of patients (12 receiving AIC and 7 receiving placebo) consented to have nasal biopsy specimens taken before immunization and before and after the first ragweed season. The preseason and postseason biopsy specimens were taken 24 hours after ragweed allergen challenge and compared with the initial unchallenged biopsy specimen to assess cytokine and inflammatory cell responses by using immunocytochemistry and in situ hybridization. Results: AIC was safe and well tolerated by all patients. There was no difference between the AIC and placebo groups in the number of allergen-induced major basic protein-, IL-4-, IL-5-, or IFN-gamma-positive cells in the mucosa in the first weeksafter AIC immunization. On rechallenge and rebiopsy after the end of the 2001 ragweed season, however, AIC-treated patients had a significantly reduced increase in eosinophils and IL-4 mRNA-positive cells and an increased number of IFN-gamma mRNA-positive cells compared with placebo-treated patients. No difference between treatment groups was observed in symptom scores or medication use during the first ragweed season. During the second ragweed season, however, there was a significant decrease in chest symptoms and a trend toward reduced nasal symptoms in the AIC-treated group. Conclusion: Short-course immunotherapy with AIC can modify the response of nasal mucosa to allergen challenge by increasing T(H)1 cytokine production and decreasing T(H)2 cytokine production and eosinophilia. This modification was not immediate but was observed 4 to 5 months after completion of immunotherapy and seasonal ragweed-pollen exposure. The T-cell subset shift after immunization and seasonal exposure was followed by evidence of clinical efficacy in the second ragweed season without additional AIC immunizations.	15	152	2004	7	10.1016/j.jaci.2003.11.001	Allergy; Immunology
A defective type 1 response to rhinovirus in atopic asthma. Background: Rhinoviruses (RVs) are the most frequent precipitants of the common cold and asthma exacerbations, but little is known about the immune response to these viruses and its potential implications in the pathogenesis of asthma. Methods: Peripheral blood mononuclear cells (PBMC) from patients with atopic asthma and normal subjects were exposed to live or inactivated RV preparations. Levels of interferon (IFN)gamma and interleukins IL-12, IL-10, IL-4, IL-5 and IL-13 were evaluated in the culture supernatants with specific immunoassays. Results: Exposure of PBMC to RVs induced the production of IFNgamma, IL-12, IL-10, and IL-13. Cells from asthmatic subjects produced significantly lower levels of IFNgamma and IL-12 and higher levels of IL-10 than normal subjects. IL-4 was induced only in the asthmatic group, while the IFNgamma/IL-4 ratio was more than three times lower in the asthmatic group. Conclusions: This evidence suggests that the immune response to RVs is not uniquely of a type 1 phenotype, as previously suggested. The type 1 response is defective in atopic asthmatic individuals, with a shift towards a type 2 phenotype in a way similar, but not identical, to their aberrant response to allergens. A defective type 1 immune response to RVs may be implicated in the pathogenesis of virus induced exacerbations of asthma.. respiratory syncytial virus| common cold virus| viral-infections| airways inflammation| gamma production| natural-killer| messenger-rna| old children| t-cells| cytokine.	APR-2002	respiratory syncytial virus| common cold virus| viral-infections| airways inflammation| gamma production| natural-killer| messenger-rna| old children| t-cells| cytokine	Papadopoulos, NG; Stanciu, LA; Papi, A; Holgate, ST; Johnston, SL	A defective type 1 response to rhinovirus in atopic asthma		THORAX		RESPIRATORY SYNCYTIAL VIRUS; COMMON COLD VIRUS; VIRAL-INFECTIONS; AIRWAYS INFLAMMATION; GAMMA PRODUCTION; NATURAL-KILLER; MESSENGER-RNA; OLD CHILDREN; T-CELLS; CYTOKINE	Background: Rhinoviruses (RVs) are the most frequent precipitants of the common cold and asthma exacerbations, but little is known about the immune response to these viruses and its potential implications in the pathogenesis of asthma. Methods: Peripheral blood mononuclear cells (PBMC) from patients with atopic asthma and normal subjects were exposed to live or inactivated RV preparations. Levels of interferon (IFN)gamma and interleukins IL-12, IL-10, IL-4, IL-5 and IL-13 were evaluated in the culture supernatants with specific immunoassays. Results: Exposure of PBMC to RVs induced the production of IFNgamma, IL-12, IL-10, and IL-13. Cells from asthmatic subjects produced significantly lower levels of IFNgamma and IL-12 and higher levels of IL-10 than normal subjects. IL-4 was induced only in the asthmatic group, while the IFNgamma/IL-4 ratio was more than three times lower in the asthmatic group. Conclusions: This evidence suggests that the immune response to RVs is not uniquely of a type 1 phenotype, as previously suggested. The type 1 response is defective in atopic asthmatic individuals, with a shift towards a type 2 phenotype in a way similar, but not identical, to their aberrant response to allergens. A defective type 1 immune response to RVs may be implicated in the pathogenesis of virus induced exacerbations of asthma.	39	152	2002	5	10.1136/thorax.57.4.328	Respiratory System
Non-Hodgkin's lymphoma and specific pesticide exposures in men: Cross-Canada study of pesticides and health. Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% Cl, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% Cl, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% Cl, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CL 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% Cl, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CL 1.40-2.75) or to mecoprop (OR, 2.22; 95% CL 1.49-3.29) and to aldrin (OR, 3.42; 95% Cl, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.. soft-tissue sarcoma| multiple-myeloma| malignant-lymphoma| cigarette-smoking| cancer mortality| risk-factors| farmers| occupations| herbicides| appliers.	NOV-2001	soft-tissue sarcoma| multiple-myeloma| malignant-lymphoma| cigarette-smoking| cancer mortality| risk-factors| farmers| occupations| herbicides| appliers	McDuffie, HH; Pahwa, P; McLaughlin, JR; Spinelli, JJ; Fincham, S; Dosman, JA; Robson, D; Skinnider, LF; Choi, NW	Non-Hodgkin's lymphoma and specific pesticide exposures in men: Cross-Canada study of pesticides and health		CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION		SOFT-TISSUE SARCOMA; MULTIPLE-MYELOMA; MALIGNANT-LYMPHOMA; CIGARETTE-SMOKING; CANCER MORTALITY; RISK-FACTORS; FARMERS; OCCUPATIONS; HERBICIDES; APPLIERS	Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% Cl, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% Cl, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% Cl, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CL 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% Cl, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CL 1.40-2.75) or to mecoprop (OR, 2.22; 95% CL 1.49-3.29) and to aldrin (OR, 3.42; 95% Cl, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.	47	152	2001	9		Oncology; Public, Environmental & Occupational Health
Evidence of a Causal Role of Winter Virus Infection during Infancy in Early Childhood Asthma. Rationale: Bronchiolitis during infancy is associated with an increased risk of childhood asthma. Whether winter viral infections cause asthma or are a manifestation of a predisposition to asthma development is unknown. Objectives: To study the relationship of winter virus infection during infancy and the development of childhood asthma. Methods: We studied over 95,000 infants born between 1995 and 2000 and followed through 2005 who were enrolled in the Tennessee Medicaid program from birth through early childhood to determine whether infant birth in relationship to the wintervirus peak alters the risk of developing early childhood asthma. Measurements and Main Results: Among 95,310 children studied during five winter virus seasons from birth through early childhood, the risk of developing asthma tracked with the timing of infant birth in relationship to the winter virus peak. Infant birth approximately 4 months before the winter virus peak carried the highest risk, with a 29% increase in odds of developing asthma compared with birth 12 months before the peak (adjusted odds ratio, 1.29; 95% confidence interval, 1.19-1.40). Infant age at the winter virus peak was comparable to or greater than other known risk factors for asthma. Conclusions: Timing of birth in relationship to winter virus season confers a differential and definable risk of developing early childhood asthma, establishing winter virus seasonality as a causal factor in asthma development. Delay of exposure or prevention of winter viral infection during early infancy could prevent asthma.. asthma| respiratory winter virus infection| timing of birth|respiratory-syncytial-virus| viral-infections| lung-disease| risk-factors| bronchiolitis| age| children| allergy| birth| pathogenesis.	DEC 1-2008	asthma| respiratory winter virus infection| timing of birth|respiratory-syncytial-virus| viral-infections| lung-disease| risk-factors| bronchiolitis| age| children| allergy| birth| pathogenesis	Wu, PS; Dupont, WD; Griffin, MR; Carroll, KN; Mitchel, EF; Gebretsadik, T; Hartert, TV	Evidence of a Causal Role of Winter Virus Infection during Infancy in Early Childhood Asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; respiratory winter virus infection; timing of birth	RESPIRATORY-SYNCYTIAL-VIRUS; VIRAL-INFECTIONS; LUNG-DISEASE; RISK-FACTORS; BRONCHIOLITIS; AGE; CHILDREN; ALLERGY; BIRTH; PATHOGENESIS	Rationale: Bronchiolitis during infancy is associated with an increased risk of childhood asthma. Whether winter viral infections cause asthma or are a manifestation of a predisposition to asthma development is unknown. Objectives: To study the relationship of winter virus infection during infancy and the development of childhood asthma. Methods: We studied over 95,000 infants born between 1995 and 2000 and followed through 2005 who were enrolled in the Tennessee Medicaid program from birth through early childhood to determine whether infant birth in relationship to the wintervirus peak alters the risk of developing early childhood asthma. Measurements and Main Results: Among 95,310 children studied during five winter virus seasons from birth through early childhood, the risk of developing asthma tracked with the timing of infant birth in relationship to the winter virus peak. Infant birth approximately 4 months before the winter virus peak carried the highest risk, with a 29% increase in odds of developing asthma compared with birth 12 months before the peak (adjusted odds ratio, 1.29; 95% confidence interval, 1.19-1.40). Infant age at the winter virus peak was comparable to or greater than other known risk factors for asthma. Conclusions: Timing of birth in relationship to winter virus season confers a differential and definable risk of developing early childhood asthma, establishing winter virus seasonality as a causal factor in asthma development. Delay of exposure or prevention of winter viral infection during early infancy could prevent asthma.	43	151	2008	7	10.1164/rccm.200804-579OC	General & Internal Medicine; Respiratory System
The impact of food allergy on the daily activities of children and their families. Background: Food allergy affects a significant number of children, and its management requires considerable time and vigilance. Objective: To determine the impact of food allergy on the daily activities of food allergic children and their families. Methods: Caregivers of food allergic children from a university-based allergy practice completed a questionnaire that evaluated their perception of the impact of their child's food allergy on family activities. Results: Of the 87 families who completed the study, more than 60% of caregivers reported that food allergy significantly affected meal preparation and 49% or more indicated that food allergy affected family social activities. Forty-one percent of parents reported a significant impact on their stress levels and 34% reported that food allergy had an impact on school attendance, with 10% choosing to home school their children because of food allergy. The number of food allergies had a significant impact on activity scores, but the existence of comorbid conditions such as asthma and atopic dermatitis did not significantly affect the results. Conclusions: Food allergy has a significant effect on activities of families of food allergic children. Further study is needed to determine more detailed effects of food allergy on parent-child interactions and development.. quality-of-life| peanut allergy| population| parents.	MAR-2006	quality-of-life| peanut allergy| population| parents	Bollinger, ME; Dahlquist, LM; Mudd, K; Sonntag, C; Dillinger, L; McKenna, K	The impact of food allergy on the daily activities of children and their families		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		QUALITY-OF-LIFE; PEANUT ALLERGY; POPULATION; PARENTS	Background: Food allergy affects a significant number of children, and its management requires considerable time and vigilance. Objective: To determine the impact of food allergy on the daily activities of food allergic children and their families. Methods: Caregivers of food allergic children from a university-based allergy practice completed a questionnaire that evaluated their perception of the impact of their child's food allergy on family activities. Results: Of the 87 families who completed the study, more than 60% of caregivers reported that food allergy significantly affected meal preparation and 49% or more indicated that food allergy affected family social activities. Forty-one percent of parents reported a significant impact on their stress levels and 34% reported that food allergy had an impact on school attendance, with 10% choosing to home school their children because of food allergy. The number of food allergies had a significant impact on activity scores, but the existence of comorbid conditions such as asthma and atopic dermatitis did not significantly affect the results. Conclusions: Food allergy has a significant effect on activities of families of food allergic children. Further study is needed to determine more detailed effects of food allergy on parent-child interactions and development.	20	151	2006	7		Allergy; Immunology
Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study. Background: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose-response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Methods: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD >= 40 and allergic sensitization to house dust mites [CAP-FEIA >= 3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2000 and 20 000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. Results: The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere-Terpstra test) and was significantly lower in the two high-dose groups (2000, 20000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel-Haenszel chi-square test). Conclusions: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.. atopic dermatitis| eczema| house dust mite| hyposensitization| specific immunotherapy|patch test| t-cells| hyposensitization| skin.	FEB-2006	atopic dermatitis| eczema| house dust mite| hyposensitization| specific immunotherapy|patch test| t-cells| hyposensitization| skin	Werfel, T; Breuer, K; Rueff, F; Przybilla, B; Worm, M; Grewe, M; Ruzicka, T; Brehler, R; Wolf, H; Schnitker, J; Kapp, A	Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study		ALLERGY	atopic dermatitis; eczema; house dust mite; hyposensitization; specific immunotherapy	PATCH TEST; T-CELLS; HYPOSENSITIZATION; SKIN	Background: The effect of specific immunotherapy (SIT) on eczema in atopic dermatitis is not known. Therefore, a multi-centre, randomized dose-response trial, double-blind with respect to the efficacy of a biologically standardized depot house dust mite preparation was performed. Methods: Eighty-nine adults with a chronic course of atopic dermatitis, SCORAD >= 40 and allergic sensitization to house dust mites [CAP-FEIA >= 3] were included, of whom 51 completed the study. Subcutaneous SIT with a house dust mite preparation (Dermatophagoides pteronyssinus/D. farinae) applying maintenance doses of 20, 2000 and 20 000 SQ-U in weekly intervals for 1 year. The main outcome measures addressed the change of the SCORAD as average of the values after 9 and 12 months of SIT in comparison with the value at baseline. Results: The SCORAD declined in the three dose groups in a dose-dependent manner (P = 0.0368, Jonckheere-Terpstra test) and was significantly lower in the two high-dose groups (2000, 20000 SQ-U) compared with the low-dose group of 20 SQ-U (P = 0.0379, U-test) after 1 year of SIT. The use of topical corticosteroids was significantly reduced with higher doses (P = 0.0007, Mantel-Haenszel chi-square test). Conclusions: Allergen-SIT for 1 year with a house dust mite preparation is able to improve the eczema in patients with atopic dermatitis who are sensitized to house dust mite allergens and reduces the need for topical corticosteroids. SIT may be valuable in the treatment of this chronic skin disease.	15	151	2006	4	10.1111/j.1398-9995.2006.00974.x	Allergy; Immunology
Multiple roles of nitric oxide in the airways. Nitric oxide is endogenously released in the airways by nitric oxide synthase. Functionally, two isoforms of this enzyme exist: constitutive and inducible. The former seems to protect airways from excessive bronchoconstriction while the latter has a modulatory role in inflammatory disorders of the airways such as asthma. This review explores the physiological and pathophysiological role of endogenous nitric oxide in the airways, and the clinical aspects of monitoring nitric oxide in exhaled air of patients with respiratory disease.. guinea-pig trachea| obstructive pulmonary-disease| vasoactive-intestinal-peptide| vascular smooth-muscle| exhaled air| in-vitro| l-arginine| asthmatic-patients| relaxing factor| mild asthma.	FEB-2003	guinea-pig trachea| obstructive pulmonary-disease| vasoactive-intestinal-peptide| vascular smooth-muscle| exhaled air| in-vitro| l-arginine| asthmatic-patients| relaxing factor| mild asthma	Ricciardolo, FLM	Multiple roles of nitric oxide in the airways		THORAX		GUINEA-PIG TRACHEA; OBSTRUCTIVE PULMONARY-DISEASE; VASOACTIVE-INTESTINAL-PEPTIDE; VASCULAR SMOOTH-MUSCLE; EXHALED AIR; IN-VITRO; L-ARGININE; ASTHMATIC-PATIENTS; RELAXING FACTOR; MILD ASTHMA	Nitric oxide is endogenously released in the airways by nitric oxide synthase. Functionally, two isoforms of this enzyme exist: constitutive and inducible. The former seems to protect airways from excessive bronchoconstriction while the latter has a modulatory role in inflammatory disorders of the airways such as asthma. This review explores the physiological and pathophysiological role of endogenous nitric oxide in the airways, and the clinical aspects of monitoring nitric oxide in exhaled air of patients with respiratory disease.	153	151	2003	8	10.1136/thorax.58.2.175	Respiratory System
Exhaled biomarkers. Assessing airway and lung inflammation is important for investigating the underlying mechanisms of asthma and COPD. Yet these cannot be measured directly in clinical research and practice because of the difficulties in monitoring inflammation. Noninvasive monitoring may assist in early recognition of asthma and COPD, assessment of its severity, and response to treatment, especially during disease exacerbations. There is increasing evidence that breath analysis may have an important place in clinical management of asthma and COPD. The article reviews the role of current noninvasive measurements of exhaled gases, such as nitric oxide (NO), inflammatory markers in exhaled breath condensate (EBC), and exhaled breath temperature, as wen as novel methods in monitoring and management of asthma and COPD.. asthma| copd| exhaled breath condensate| exhaled nitric oxide|nitric-oxide measurements| obstructive pulmonary-disease| breath condensate| asthma| copd| lung| markers| prostaglandins| leukotrienes| air.	NOV-2006	asthma| copd| exhaled breath condensate| exhaled nitric oxide|nitric-oxide measurements| obstructive pulmonary-disease| breath condensate| asthma| copd| lung| markers| prostaglandins| leukotrienes| air	Kharitonov, SA; Barnes, PJ	Exhaled biomarkers		CHEST	asthma; COPD; exhaled breath condensate; exhaled nitric oxide	NITRIC-OXIDE MEASUREMENTS; OBSTRUCTIVE PULMONARY-DISEASE; BREATH CONDENSATE; ASTHMA; COPD; LUNG; MARKERS; PROSTAGLANDINS; LEUKOTRIENES; AIR	Assessing airway and lung inflammation is important for investigating the underlying mechanisms of asthma and COPD. Yet these cannot be measured directly in clinical research and practice because of the difficulties in monitoring inflammation. Noninvasive monitoring may assist in early recognition of asthma and COPD, assessment of its severity, and response to treatment, especially during disease exacerbations. There is increasing evidence that breath analysis may have an important place in clinical management of asthma and COPD. The article reviews the role of current noninvasive measurements of exhaled gases, such as nitric oxide (NO), inflammatory markers in exhaled breath condensate (EBC), and exhaled breath temperature, as wen as novel methods in monitoring and management of asthma and COPD.	27	150	2006	6	10.1378/chest.130.5.1541	General & Internal Medicine; Respiratory System
Asthma control in the Asia-Pacific region: The asthma insights and reality in Asia-Pacific study. Background: Few data on asthma management are available for the Asia-Pacific region. Objective: This study examined asthma symptoms, health care use, and management in the Asia-Pacific region. Methods: We performed a cross-sectional survey, followed by administration of a questionnaire in a face-to-face setting in the respondents' homes in their language of choice. Urban centers in 8 areas were surveyed: China, Hong Kong, Korea, Malaysia, The Philippines, Singapore, Taiwan, and Vietnam. Results: A population sample of 3207 respondents with physician-diagnosed asthma was identified by screening 108,360 households. Daytime asthma symptoms were reported by 51.4% of respondents, and 44.3% reported sleep disturbance caused by asthma in the preceding 4 weeks. At least 2 in every 5 respondents (43.6%) had been hospitalized, attended a hospital emergency department, or made unscheduled emergency visits to other health care facilities for treatment of asthma during the previous 12 months. Overall, 15.3% of respondents reported that they had required admission to the hospital for asthma treatment. Asthma severity correlated with the frequencies of hospitalizations and emergency visits for asthma in the past year. Even in those patients with severe persistent asthma, 34.3% regarded their disease as being well or completely controlled. Current use of an inhaled corticosteroid was reported by only 13.6% of respondents, and 56.3% used quick-relief bronchodilators. Absence from school and work in the past year was reported by 36.5 % of children and 26.5 % of adults. Conclusion: As reported for other regions, current levels of asthma control in the Asia-Pacific region fall markedly short of goals specified in international guidelines for asthma management. (J Allergy Clin Immunol 2003; 111:263-8.).. asia| asthma epidemiology| asthma control| asthma management| inhaled corticosteroids|hong-kong| prevalence| guidelines| management| epidemiology| population| isaac.	FEB-2003	asia| asthma epidemiology| asthma control| asthma management| inhaled corticosteroids|hong-kong| prevalence| guidelines| management| epidemiology| population| isaac	Lai, CKW; de Guia, TS; Kim, YY; Kuo, SH; Mukhopadhyay, A; Soriano, JB; Trung, PL; Zhong, NS; Zainudin, N; Zainudin, BMZ	Asthma control in the Asia-Pacific region: The asthma insights and reality in Asia-Pacific study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Asia; asthma epidemiology; asthma control; asthma management; inhaled corticosteroids	HONG-KONG; PREVALENCE; GUIDELINES; MANAGEMENT; EPIDEMIOLOGY; POPULATION; ISAAC	Background: Few data on asthma management are available for the Asia-Pacific region. Objective: This study examined asthma symptoms, health care use, and management in the Asia-Pacific region. Methods: We performed a cross-sectional survey, followed by administration of a questionnaire in a face-to-face setting in the respondents' homes in their language of choice. Urban centers in 8 areas were surveyed: China, Hong Kong, Korea, Malaysia, The Philippines, Singapore, Taiwan, and Vietnam. Results: A population sample of 3207 respondents with physician-diagnosed asthma was identified by screening 108,360 households. Daytime asthma symptoms were reported by 51.4% of respondents, and 44.3% reported sleep disturbance caused by asthma in the preceding 4 weeks. At least 2 in every 5 respondents (43.6%) had been hospitalized, attended a hospital emergency department, or made unscheduled emergency visits to other health care facilities for treatment of asthma during the previous 12 months. Overall, 15.3% of respondents reported that they had required admission to the hospital for asthma treatment. Asthma severity correlated with the frequencies of hospitalizations and emergency visits for asthma in the past year. Even in those patients with severe persistent asthma, 34.3% regarded their disease as being well or completely controlled. Current use of an inhaled corticosteroid was reported by only 13.6% of respondents, and 56.3% used quick-relief bronchodilators. Absence from school and work in the past year was reported by 36.5 % of children and 26.5 % of adults. Conclusion: As reported for other regions, current levels of asthma control in the Asia-Pacific region fall markedly short of goals specified in international guidelines for asthma management. (J Allergy Clin Immunol 2003; 111:263-8.).	20	150	2003	6	10.1067/mai.2003.30	Allergy; Immunology
Increased asthma medication use in association with ambient fine and ultrafine particles. The association between particulate air pollution and asthma medication use and symptoms was assessed in a panel study of 53 adult asthmatics in Erfurt, Germany in winter 1996/1997. Number concentrations of ultrafine particles, 0.01-0.1 mum in diameter (NC0.01-0.1), mean 17,300.cm(-3), and mass concentrations of fine particles 0.01-2.5 mum in diameter (MC0.01-2.5), mean 30.3 mug.m(-3), were measured concurrently. They were not highly correlated (r=0.45). The associations between ambient particle concentrations and the prevalence of inhaled beta(2)-agonist, corticosteroid use and asthma symptoms, were analysed separately with logistic regression models, adjusting for trend, temperature, weekend, holidays, and first order autocorrelation of the error. Cumulative exposures over 14 days of ultrafine and fine particles were associated with corticosteroid use. beta(2)-agonist use was associated with 5-day mean NC0.01-0.1 and MC0.01-2.5. The prevalence of asthma symptoms was associated with ambient particle concentrations. The results suggest that reported asthma medication use and symptoms increase in association with particulate air pollution and gaseous pollutants such as nitrogen dioxide.. asthma symptoms| inhaled beta(2)-agonists| inhaled corticosteroids| particulate air pollution| wheezing|particulate air-pollution| peak expiratory flow| chronic respiratory symptoms| time-series| urban air| longitudinal data| pm10 pollution| health| children| models.	SEP-2002	asthma symptoms| inhaled beta(2)-agonists| inhaled corticosteroids| particulate air pollution| wheezing|particulate air-pollution| peak expiratory flow| chronic respiratory symptoms| time-series| urban air| longitudinal data| pm10 pollution| health| children| models	von Klot, S; Wolke, G; Tuch, T; Heinrich, J; Dockery, DW; Schwartz, J; Kreyling, WG; Wichmann, HE; Peters, A	Increased asthma medication use in association with ambient fine and ultrafine particles		EUROPEAN RESPIRATORY JOURNAL	asthma symptoms; inhaled beta(2)-agonists; inhaled corticosteroids; particulate air pollution; wheezing	PARTICULATE AIR-POLLUTION; PEAK EXPIRATORY FLOW; CHRONIC RESPIRATORY SYMPTOMS; TIME-SERIES; URBAN AIR; LONGITUDINAL DATA; PM10 POLLUTION; HEALTH; CHILDREN; MODELS	The association between particulate air pollution and asthma medication use and symptoms was assessed in a panel study of 53 adult asthmatics in Erfurt, Germany in winter 1996/1997. Number concentrations of ultrafine particles, 0.01-0.1 mum in diameter (NC0.01-0.1), mean 17,300.cm(-3), and mass concentrations of fine particles 0.01-2.5 mum in diameter (MC0.01-2.5), mean 30.3 mug.m(-3), were measured concurrently. They were not highly correlated (r=0.45). The associations between ambient particle concentrations and the prevalence of inhaled beta(2)-agonist, corticosteroid use and asthma symptoms, were analysed separately with logistic regression models, adjusting for trend, temperature, weekend, holidays, and first order autocorrelation of the error. Cumulative exposures over 14 days of ultrafine and fine particles were associated with corticosteroid use. beta(2)-agonist use was associated with 5-day mean NC0.01-0.1 and MC0.01-2.5. The prevalence of asthma symptoms was associated with ambient particle concentrations. The results suggest that reported asthma medication use and symptoms increase in association with particulate air pollution and gaseous pollutants such as nitrogen dioxide.	42	150	2002	12	10.1183/09031936.02.01402001	Respiratory System
Intestinal permeation and gastrointestinal disease. The gastrointestinal tract constitutes one of the largest sites of exposure to the outside environment. The function of the gastrointestinal tract in monitoring and sealing the host interior from intruders is called the gut barrier. A variety of specific and nonspecific mechanisms are in operation to establish the host barrier: these include luminal mechanisms and digestive enzymes, the epithelial cells together with tight junctions in between them, and the gut immune system. Disruptions in the gut barrier follow injury from various causes including nonsteroidal anti-inflammatory drugs and oxidant stress, and involve mechanisms such as adenosine triphosphate depletion and damage to epithelial cell cytoskeletons that regulate tight junctions. Ample evidence links gut barrier dysfunction to multiorgan system failure in sepsis and immune dysregulation. Additionally, contribution of gut barrier dysfunction to gastrointestinal disease is an evolving concept and is the focus of this review. An overview of the evidence for the role of gut barrier dysfunction in disorders such as Crohn's disease, celiac disease. food allergy, acute pancreatitis, non-alcoholic fatty liver disease., and alcoholic liver disease is provided, together with critical insight into the implications of this evidence as a primary disease mechanism.. intestinal permeation| gastrointestinal disease| gastrointestinal tract|inflammatory-bowel-disease| multiple organ failure| severe acute-pancreatitis| first-degree relatives| 1st degree relatives| cows milk allergy| crohns-disease| bacterial translocation| celiac-disease| increased permeability.	APR-2002	intestinal permeation| gastrointestinal disease| gastrointestinal tract|inflammatory-bowel-disease| multiple organ failure| severe acute-pancreatitis| first-degree relatives| 1st degree relatives| cows milk allergy| crohns-disease| bacterial translocation| celiac-disease| increased permeability	DeMeo, MT; Mutlu, EA; Keshavarzian, A; Tobin, MC	Intestinal permeation and gastrointestinal disease		JOURNAL OF CLINICAL GASTROENTEROLOGY	intestinal permeation; gastrointestinal disease; gastrointestinal tract	INFLAMMATORY-BOWEL-DISEASE; MULTIPLE ORGAN FAILURE; SEVERE ACUTE-PANCREATITIS; FIRST-DEGREE RELATIVES; 1ST DEGREE RELATIVES; COWS MILK ALLERGY; CROHNS-DISEASE; BACTERIAL TRANSLOCATION; CELIAC-DISEASE; INCREASED PERMEABILITY	The gastrointestinal tract constitutes one of the largest sites of exposure to the outside environment. The function of the gastrointestinal tract in monitoring and sealing the host interior from intruders is called the gut barrier. A variety of specific and nonspecific mechanisms are in operation to establish the host barrier: these include luminal mechanisms and digestive enzymes, the epithelial cells together with tight junctions in between them, and the gut immune system. Disruptions in the gut barrier follow injury from various causes including nonsteroidal anti-inflammatory drugs and oxidant stress, and involve mechanisms such as adenosine triphosphate depletion and damage to epithelial cell cytoskeletons that regulate tight junctions. Ample evidence links gut barrier dysfunction to multiorgan system failure in sepsis and immune dysregulation. Additionally, contribution of gut barrier dysfunction to gastrointestinal disease is an evolving concept and is the focus of this review. An overview of the evidence for the role of gut barrier dysfunction in disorders such as Crohn's disease, celiac disease. food allergy, acute pancreatitis, non-alcoholic fatty liver disease., and alcoholic liver disease is provided, together with critical insight into the implications of this evidence as a primary disease mechanism.	108	150	2002	12	10.1097/00004836-200204000-00003	Gastroenterology & Hepatology
Exposure to pets and atopy-related diseases in the first 4 years of life. Background: It is still unclear how early-life exposure to pets is related to children's risk of developing atopy-related diseases. We estimated associations between early-life exposure to pets and atopy-related diseases at 0-4 years of life in a cohort of Norwegian children. Methods: A population-based cohort of 2531 children born in Oslo, Norway, was followed from birth to the age of 4 years. Information on early-life exposure to pets, a number of possible confounders, and atopy-related diseases was mainly collected by questionnaire. Results: In logistic regression analysis adjusting for potential confounders, the odds ratio for being exposed to pets in early life (reference category: not exposed) was, for bronchial obstruction at 0-2 years of life, 1.2 (95% confidence interval 0.9, 1.8); for asthma at the age of 4 years, 0.7 (0.5, 1.1); for allergic rhinitis at the age of 4 years, 0.6 (0.4, 1.0); and for atopic eczema at 0-6 months of life, 0.7 (0.5, 0.9). Conclusions: The results indicate that early-life exposure to pets or lifestyle factors associated with, exposure to pets reduce the risk of developing atopy-related diseases in early childhood. However, these findings might also be explained by selection for keeping pets.. allergic rhinitis| asthma| atopy| children| epidemiology| pets|risk-factors| respiratory health| furred pets| hay-fever| sensitization| asthma| children| allergy| cat| environment.	APR-2001	allergic rhinitis| asthma| atopy| children| epidemiology| pets|risk-factors| respiratory health| furred pets| hay-fever| sensitization| asthma| children| allergy| cat| environment	Nafstad, P; Magnus, P; Gaarder, PI; Jaakkola, JJK	Exposure to pets and atopy-related diseases in the first 4 years of life		ALLERGY	allergic rhinitis; asthma; atopy; children; epidemiology; pets	RISK-FACTORS; RESPIRATORY HEALTH; FURRED PETS; HAY-FEVER; SENSITIZATION; ASTHMA; CHILDREN; ALLERGY; CAT; ENVIRONMENT	Background: It is still unclear how early-life exposure to pets is related to children's risk of developing atopy-related diseases. We estimated associations between early-life exposure to pets and atopy-related diseases at 0-4 years of life in a cohort of Norwegian children. Methods: A population-based cohort of 2531 children born in Oslo, Norway, was followed from birth to the age of 4 years. Information on early-life exposure to pets, a number of possible confounders, and atopy-related diseases was mainly collected by questionnaire. Results: In logistic regression analysis adjusting for potential confounders, the odds ratio for being exposed to pets in early life (reference category: not exposed) was, for bronchial obstruction at 0-2 years of life, 1.2 (95% confidence interval 0.9, 1.8); for asthma at the age of 4 years, 0.7 (0.5, 1.1); for allergic rhinitis at the age of 4 years, 0.6 (0.4, 1.0); and for atopic eczema at 0-6 months of life, 0.7 (0.5, 0.9). Conclusions: The results indicate that early-life exposure to pets or lifestyle factors associated with, exposure to pets reduce the risk of developing atopy-related diseases in early childhood. However, these findings might also be explained by selection for keeping pets.	25	150	2001	6	10.1034/j.1398-9995.2001.00881.x	Allergy; Immunology
Air quality and pediatric emergency room visits for asthma in Atlanta, Georgia. Pediatric emergency room visits for asthma were studied in relation to air quality indices in a spatio-temporal investigation of approximately 130,000 visits (similar to 6,000 for asthma) to the major emergency care centers in Atlanta, Georgia, during the summers of 1993-1995, Generalized estimating equations, logistic regression, and Bayesian models were fitted to the data. in logistic regression models comparing estimated exposures of asthma cases with those of the nonasthma patients, controlling for temporal and demographic covariates and using residential zip code to link patients to spatially resolved ozone levels, the estimated relative risk per 20 parts per billion (ppb) increase in the maximum 8-hour ozone level was 1.04 (p < 0.05). The estimated relative risk for particulate matter less than or equal to 10 mu m in aerodynamic diameter (PM10) was 1.04 per 15 mu g/m(3) (p < 0.05). Exposure-response trends (p < 0.01) were observed for ozone (>100 ppb vs. <50 ppb: odds ratio = 1.23, p = 0.003) and PM10 (>60 mu g/m(3) vs. <20 mu g/m(3): odds ratio = 1.26, p = 0.004). In models with ozone and PM10, both terms became nonsignificant because of collinearity of the variables (r = 0.75), The other analytical approaches yielded consistent findings. This study supports accumulating evidence regarding the relation of air pollution to childhood asthma exacerbation.. air pollution| asthma| child| emergency service, hospital| ozone|hospital admissions| respiratory health| childhood asthma| mexico-city| pollution| ozone.	APR 15-2000	air pollution| asthma| child| emergency service, hospital| ozone|hospital admissions| respiratory health| childhood asthma| mexico-city| pollution| ozone	Tolbert, PE; Mulholland, JA; MacIntosh, DL; Xu, F; Daniels, D; Devine, OJ; Carlin, BP; Klein, M; Dorley, J; Butler, AJ; Nordenberg, DF; Frumkin, H; Ryan, PB; White, MC	Air quality and pediatric emergency room visits for asthma in Atlanta, Georgia		AMERICAN JOURNAL OF EPIDEMIOLOGY	air pollution; asthma; child; emergency service, hospital; ozone	HOSPITAL ADMISSIONS; RESPIRATORY HEALTH; CHILDHOOD ASTHMA; MEXICO-CITY; POLLUTION; OZONE	Pediatric emergency room visits for asthma were studied in relation to air quality indices in a spatio-temporal investigation of approximately 130,000 visits (similar to 6,000 for asthma) to the major emergency care centers in Atlanta, Georgia, during the summers of 1993-1995, Generalized estimating equations, logistic regression, and Bayesian models were fitted to the data. in logistic regression models comparing estimated exposures of asthma cases with those of the nonasthma patients, controlling for temporal and demographic covariates and using residential zip code to link patients to spatially resolved ozone levels, the estimated relative risk per 20 parts per billion (ppb) increase in the maximum 8-hour ozone level was 1.04 (p < 0.05). The estimated relative risk for particulate matter less than or equal to 10 mu m in aerodynamic diameter (PM10) was 1.04 per 15 mu g/m(3) (p < 0.05). Exposure-response trends (p < 0.01) were observed for ozone (>100 ppb vs. <50 ppb: odds ratio = 1.23, p = 0.003) and PM10 (>60 mu g/m(3) vs. <20 mu g/m(3): odds ratio = 1.26, p = 0.004). In models with ozone and PM10, both terms became nonsignificant because of collinearity of the variables (r = 0.75), The other analytical approaches yielded consistent findings. This study supports accumulating evidence regarding the relation of air pollution to childhood asthma exacerbation.	26	150	2000	13		Public, Environmental & Occupational Health
Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Background: Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD. Methods: In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV1) 61.0 (12.6)% predicted) received 500 mu g roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly. Results: Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and alpha(2)-macroglobulin in sputum and the release of tumour necrosis factor alpha from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV1 improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018). Conclusion: PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV1.. obstructive pulmonary-disease| air-flow limitation| phosphodiesterase-4 inhibitor| lung-function| systemic inflammation| asthma| metaanalysis| fluticasone| propionate| modulation.	DEC-2007	obstructive pulmonary-disease| air-flow limitation| phosphodiesterase-4 inhibitor| lung-function| systemic inflammation| asthma| metaanalysis| fluticasone| propionate| modulation	Grootendorst, DC; Gauw, SA; Verhoosel, RM; Sterk, PJ; Hospers, JJ; Bredenbroker, D; Bethke, TD; Hiemstra, PS; Rabe, KF	Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD		THORAX		OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW LIMITATION; PHOSPHODIESTERASE-4 INHIBITOR; LUNG-FUNCTION; SYSTEMIC INFLAMMATION; ASTHMA; METAANALYSIS; FLUTICASONE; PROPIONATE; MODULATION	Background: Roflumilast is a targeted oral once-daily administered phosphodiesterase 4 (PDE4) inhibitor with clinical efficacy in chronic obstructive pulmonary disease (COPD). Results from in vitro studies with roflumilast indicate that it has anti-inflammatory properties that may be applicable for the treatment of COPD. Methods: In a crossover study, 38 patients with COPD (mean (SD) age 63.1 (7.0) years, post-bronchodilator forced expiratory volume in 1 s (FEV1) 61.0 (12.6)% predicted) received 500 mu g roflumilast or placebo once daily for 4 weeks. Induced sputum samples were collected before and after 2 and 4 weeks of treatment. Differential and absolute cell counts were determined in whole sputum samples. Markers of inflammation were determined in sputum supernatants and blood. Spirometry was performed weekly. Results: Roflumilast significantly reduced the absolute number of neutrophils and eosinophils/g sputum compared with placebo by 35.5% (95% CI 15.6% to 50.7%; p = 0.002) and 50.0% (95% CI 26.8% to 65.8%; p<0.001), respectively. The relative proportion of sputum neutrophils and eosinophils was not affected by treatment (p>0.05). Levels of soluble interleukin-8, neutrophil elastase, eosinophil cationic protein and alpha(2)-macroglobulin in sputum and the release of tumour necrosis factor alpha from blood cells were significantly reduced by roflumilast compared with placebo treatment (p<0.05 for all). Post-bronchodilator FEV1 improved significantly during roflumilast compared with placebo treatment with a mean difference between treatments of 68.7 ml (95% CI 12.9 to 124.5; p = 0.018). Conclusion: PDE4 inhibition by roflumilast treatment for 4 weeks reduced the number of neutrophils and eosinophils, as well as soluble markers of neutrophilic and eosinophilic inflammatory activity in induced sputum samples of patients with COPD. This anti-inflammatory effect may in part explain the concomitant improvement in post-bronchodilator FEV1.	39	149	2007	7	10.1136/thx.2006.075937	Respiratory System
Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle - the PARSIFAL study. Background: The prevalence of allergic diseases has increased rapidly in recent decades, particularly in children. For adequate prevention it is important not only to identify risk factors, but also possible protective factors. The aim of this study was to compare the prevalence of allergic diseases and sensitization between farm children, children in anthroposophic families, and reference children, with the aim to identify factors that may protect against allergic disease. Methods: The study was of cross-sectional design and included 14 893 children, aged 5-13 years, from farm families, anthroposophic families (recruited from Steiner schools) and reference children in Austria, Germany, the Netherlands, Sweden and Switzerland. A detailed questionnaire was completed and allergen-specific IgE was measured in blood. Results: Growing up on a farm was found to have a protective effect against all outcomes studied, both self-reported, such as rhinoconjunctivitis, wheezing, atopic eczema and asthma and sensitization (allergen specific IgE >= 0.35 kU/l). The adjusted odds ratio (OR) for current rhinoconjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and for atopic sensitization 0.53 (95% CI 0.42-0.67) for the farm children compared to their references. The prevalence of allergic symptoms and sensitization was also lower among Steiner school children compared to reference children, but the difference was less pronounced and not as consistent between countries, adjusted OR for current rhinoconjunctivitis symptoms was 0.69 (95% CI 0.56-0.86) and for atopic sensitization 0.73 (95% CI 0.58-0.92). Conclusions: This study indicates that growing up on a farm, and to a lesser extent leading an anthroposophic life style may confer protection from both sensitization and allergic diseases in childhood.. asthma| environment| epidemiology| paediatrics| rhinitis|house-dust endotoxin| hay-fever| farmers children| birth cohort| asthma| exposure| prevalence| childhood| schoolchildren| symptoms.	APR-2006	asthma| environment| epidemiology| paediatrics| rhinitis|house-dust endotoxin| hay-fever| farmers children| birth cohort| asthma| exposure| prevalence| childhood| schoolchildren| symptoms	Alfven, T; Braun-Fahrlander, C; Brunekreef, B; von Mutius, E; Riedler, J; Scheynius, A; van Hage, M; Wickman, M; Benz, MR; Budde, J; Michels, KB; Schram, D; Ublagger, E; Waser, M; Pershagen, G	Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle - the PARSIFAL study		ALLERGY	asthma; environment; epidemiology; paediatrics; rhinitis	HOUSE-DUST ENDOTOXIN; HAY-FEVER; FARMERS CHILDREN; BIRTH COHORT; ASTHMA; EXPOSURE; PREVALENCE; CHILDHOOD; SCHOOLCHILDREN; SYMPTOMS	Background: The prevalence of allergic diseases has increased rapidly in recent decades, particularly in children. For adequate prevention it is important not only to identify risk factors, but also possible protective factors. The aim of this study was to compare the prevalence of allergic diseases and sensitization between farm children, children in anthroposophic families, and reference children, with the aim to identify factors that may protect against allergic disease. Methods: The study was of cross-sectional design and included 14 893 children, aged 5-13 years, from farm families, anthroposophic families (recruited from Steiner schools) and reference children in Austria, Germany, the Netherlands, Sweden and Switzerland. A detailed questionnaire was completed and allergen-specific IgE was measured in blood. Results: Growing up on a farm was found to have a protective effect against all outcomes studied, both self-reported, such as rhinoconjunctivitis, wheezing, atopic eczema and asthma and sensitization (allergen specific IgE >= 0.35 kU/l). The adjusted odds ratio (OR) for current rhinoconjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and for atopic sensitization 0.53 (95% CI 0.42-0.67) for the farm children compared to their references. The prevalence of allergic symptoms and sensitization was also lower among Steiner school children compared to reference children, but the difference was less pronounced and not as consistent between countries, adjusted OR for current rhinoconjunctivitis symptoms was 0.69 (95% CI 0.56-0.86) and for atopic sensitization 0.73 (95% CI 0.58-0.92). Conclusions: This study indicates that growing up on a farm, and to a lesser extent leading an anthroposophic life style may confer protection from both sensitization and allergic diseases in childhood.	25	149	2006	8	10.1111/j.1398-9995.2005.00939.x	Allergy; Immunology
Asthma as a risk factor for COPD in a longitudinal study. Background: For several years, asthma and COPD have been regarded as distinct entities, with distinct clinical courses. However, despite distinctive physiologic features at the time of diagnosis, and different risk factors, the two diseases over time may develop features that are quite similar. Study objective: To evaluate the association between physician-diagnosed asthma and the subsequent development of COPD in a cohort of 3,099 adult subjects from Tucson, AZ. Design and methods: A prospective observational study. Participants completed up to 12 standard respiratory questionnaires and 11 spirometry lung function measurements over a period of 20 years. Survival curves (with time to development of COPD as the dependent variable) were compared between subjects with asthma and subjects without asthma at the initial survey. Results: Subjects with active asthma (n = 192) had significantly higher hazard ratios than inactive (n = 156) or nonasthmatic subjects (n = 2751) for acquiring COPD. As compared with nonasthmatics, active asthmatics had a 10-times-higher risk for acquiring symptoms of chronic bronchitis (95% confidence interval [CI], 4.94 to 20.25), 17-times-higher risk of receiving a diagnosis of emphysema (95% CI, 8.31 to 34.83), and 12.5-times-higher risk of fulfilling COPD criteria (95% CI, 6.84 to 22.84), even after adjusting for smoking history and other potential confounders. Conclusions: Physician-diagnosed asthma is significantly associated with an increased risk for CB, emphysema, and COPD.. asthma| chronic bronchitis| copd| pulmonary emphysema|monoxide diffusing-capacity| air-flow obstruction| skin-test reactivity| respiratory symptoms| pulmonary-function| bronchial responsiveness| population sample| lung-function| serum ige| follow-up.	JUL-2004	asthma| chronic bronchitis| copd| pulmonary emphysema|monoxide diffusing-capacity| air-flow obstruction| skin-test reactivity| respiratory symptoms| pulmonary-function| bronchial responsiveness| population sample| lung-function| serum ige| follow-up	Silva, GE; Sherrill, DL; Guerra, S; Barbee, RA	Asthma as a risk factor for COPD in a longitudinal study		CHEST	asthma; chronic bronchitis; COPD; pulmonary emphysema	MONOXIDE DIFFUSING-CAPACITY; AIR-FLOW OBSTRUCTION; SKIN-TEST REACTIVITY; RESPIRATORY SYMPTOMS; PULMONARY-FUNCTION; BRONCHIAL RESPONSIVENESS; POPULATION SAMPLE; LUNG-FUNCTION; SERUM IGE; FOLLOW-UP	Background: For several years, asthma and COPD have been regarded as distinct entities, with distinct clinical courses. However, despite distinctive physiologic features at the time of diagnosis, and different risk factors, the two diseases over time may develop features that are quite similar. Study objective: To evaluate the association between physician-diagnosed asthma and the subsequent development of COPD in a cohort of 3,099 adult subjects from Tucson, AZ. Design and methods: A prospective observational study. Participants completed up to 12 standard respiratory questionnaires and 11 spirometry lung function measurements over a period of 20 years. Survival curves (with time to development of COPD as the dependent variable) were compared between subjects with asthma and subjects without asthma at the initial survey. Results: Subjects with active asthma (n = 192) had significantly higher hazard ratios than inactive (n = 156) or nonasthmatic subjects (n = 2751) for acquiring COPD. As compared with nonasthmatics, active asthmatics had a 10-times-higher risk for acquiring symptoms of chronic bronchitis (95% confidence interval [CI], 4.94 to 20.25), 17-times-higher risk of receiving a diagnosis of emphysema (95% CI, 8.31 to 34.83), and 12.5-times-higher risk of fulfilling COPD criteria (95% CI, 6.84 to 22.84), even after adjusting for smoking history and other potential confounders. Conclusions: Physician-diagnosed asthma is significantly associated with an increased risk for CB, emphysema, and COPD.	34	149	2004	7	10.1378/chest.126.1.59	General & Internal Medicine; Respiratory System
Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease. Background: Aspirin desensitization treatment is an option to decrease disease activity and reduce the need for systemic corticosteroids in patients with aspirin-exacerbated respiratory disease (AERD). Objective: This study was designed to determine whether the clinical courses of patients with AERD improved as early as 6 months after starting aspirin desensitization and to compare this with follow-up evaluations after at least a year. Methods: Between 1995 and 2000, 172 patients with AERD were admitted to our General Clinical Research Center, were desensitized to and treated with aspirin, were discharged to their home communities, and participated in follow-up interviews and written assessments of their clinical courses. Results: By the first 6 months of aspirin treatment, there were significant reductions in sinus infections and numbers of short courses of prednisone and improvements in sense of smell and general assessment of nasal-sinus and asthma symptoms (P <.0001). These results persisted for I to 5 years (P <.0001). Mean prednisone doses decreased from 10.8 mg/d to 8.1 and 3.6 mg/d at 6 months and greater than 1 year, respectively. Of the 172 patients, 24 (14%) discontinued aspirin treatment because of side effects, and 115 (67%) responded to aspirin treatment. After eliminating those who discontinued aspirin treatment because of side effects, the improvement rate was 115 (78%) of 148 patients. Of the 126 patients who completed a year or more of aspirin treatment, 110 (87%) experienced improvement. Conclusion: Aspirin desensitization followed by daily aspirin is efficacious by at least the first 6 months of treatment and continues to be effective for up to 5 years of follow-up.. aspirin| asthma| rhinitis| desensitization| nonsteroidal anti-inflammatory drugs| aspirin desensitization treatment|rhinosinusitis-asthma| challenges.	JAN-2003	aspirin| asthma| rhinitis| desensitization| nonsteroidal anti-inflammatory drugs| aspirin desensitization treatment|rhinosinusitis-asthma| challenges	Berges-Gimeno, MP; Simon, RA; Stevenson, DD	Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	aspirin; asthma; rhinitis; desensitization; nonsteroidal anti-inflammatory drugs; aspirin desensitization treatment	RHINOSINUSITIS-ASTHMA; CHALLENGES	Background: Aspirin desensitization treatment is an option to decrease disease activity and reduce the need for systemic corticosteroids in patients with aspirin-exacerbated respiratory disease (AERD). Objective: This study was designed to determine whether the clinical courses of patients with AERD improved as early as 6 months after starting aspirin desensitization and to compare this with follow-up evaluations after at least a year. Methods: Between 1995 and 2000, 172 patients with AERD were admitted to our General Clinical Research Center, were desensitized to and treated with aspirin, were discharged to their home communities, and participated in follow-up interviews and written assessments of their clinical courses. Results: By the first 6 months of aspirin treatment, there were significant reductions in sinus infections and numbers of short courses of prednisone and improvements in sense of smell and general assessment of nasal-sinus and asthma symptoms (P <.0001). These results persisted for I to 5 years (P <.0001). Mean prednisone doses decreased from 10.8 mg/d to 8.1 and 3.6 mg/d at 6 months and greater than 1 year, respectively. Of the 172 patients, 24 (14%) discontinued aspirin treatment because of side effects, and 115 (67%) responded to aspirin treatment. After eliminating those who discontinued aspirin treatment because of side effects, the improvement rate was 115 (78%) of 148 patients. Of the 126 patients who completed a year or more of aspirin treatment, 110 (87%) experienced improvement. Conclusion: Aspirin desensitization followed by daily aspirin is efficacious by at least the first 6 months of treatment and continues to be effective for up to 5 years of follow-up.	18	149	2003	7	10.1067/mai.2003.7	Allergy; Immunology
Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis. Abnormal apoptotic mechanisms are associated with disease pathogenesis. Because the asthmatic bronchial epithelium is characteristically damaged with loss of columnar epithelial cells, we postulated that this is due to unscheduled apoptosis. Using an antibody directed toward the caspase cleavage product of poly(ADP-ribose) polymerase, immunohistochemistry applied to endobronchial biopsies showed higher levels of staining in the bronchial epithelium of subjects with asthma as compared with normal control subjects (% epithelial staining [median (range) = 10.5 (1.4-24.5) versus 0.4 (0.0-9.7)]; P < 0.001). Because we were unable to determine whether this difference was due to ongoing inflammation in vivo, cultures of normal and asthmatic bronchial epithelial cells were used to study apoptosis in vitro. In complete growth medium, these cells showed no difference in their rate of proliferation or viability. However, cells from subjects with asthma were more susceptible to the apoptotic effects of H2O2 than cells from normal control subjects (% apoptotic cells = 32.2 [8.8-54.9] versus 14.3 [6.4-24.7]; P < 0.05), even though both were similarly affected by treatment with actinomycin D. These data indicate that the susceptibility of asthmatic bronchial epithelium to oxidants is greater than normal. This susceptibility may contribute to the rising trends in asthma associated with air pollution and diets low in antioxidants.. nonasthmatic subjects| factor receptor| cells| airway| expression| hyperreactivity| proliferation| antioxidants| inflammation| biopsies.	AUG-2002	nonasthmatic subjects| factor receptor| cells| airway| expression| hyperreactivity| proliferation| antioxidants| inflammation| biopsies	Bucchieri, F; Puddicombe, SM; Lordan, JL; Richter, A; Buchanan, D; Wilson, SJ; Ward, J; Zummo, G; Howarth, PH; Djukanovic, R; Holgate, ST; Davies, DE	Asthmatic bronchial epithelium is more susceptible to oxidant-induced apoptosis		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		NONASTHMATIC SUBJECTS; FACTOR RECEPTOR; CELLS; AIRWAY; EXPRESSION; HYPERREACTIVITY; PROLIFERATION; ANTIOXIDANTS; INFLAMMATION; BIOPSIES	Abnormal apoptotic mechanisms are associated with disease pathogenesis. Because the asthmatic bronchial epithelium is characteristically damaged with loss of columnar epithelial cells, we postulated that this is due to unscheduled apoptosis. Using an antibody directed toward the caspase cleavage product of poly(ADP-ribose) polymerase, immunohistochemistry applied to endobronchial biopsies showed higher levels of staining in the bronchial epithelium of subjects with asthma as compared with normal control subjects (% epithelial staining [median (range) = 10.5 (1.4-24.5) versus 0.4 (0.0-9.7)]; P < 0.001). Because we were unable to determine whether this difference was due to ongoing inflammation in vivo, cultures of normal and asthmatic bronchial epithelial cells were used to study apoptosis in vitro. In complete growth medium, these cells showed no difference in their rate of proliferation or viability. However, cells from subjects with asthma were more susceptible to the apoptotic effects of H2O2 than cells from normal control subjects (% apoptotic cells = 32.2 [8.8-54.9] versus 14.3 [6.4-24.7]; P < 0.05), even though both were similarly affected by treatment with actinomycin D. These data indicate that the susceptibility of asthmatic bronchial epithelium to oxidants is greater than normal. This susceptibility may contribute to the rising trends in asthma associated with air pollution and diets low in antioxidants.	38	149	2002	7		Biochemistry & Molecular Biology; Cell Biology; Respiratory System
A restricted subset of dendritic cells captures airborne antigens and remains able to activate specific T cells long after antigen exposure. Mice sensitized for a Th2 response to Leishmania LACK antigen developed allergic airway inflammation upon exposure to LACK aerosol. Using multimers of I-A(d) molecules bound to a LACK peptide as probes, we tracked the migration of LACK-specific Th2 cells to the airways. Elevated numbers of LACK-specific Th2 cells remained in the airways for 5 weeks after the last aerosol. Substantial numbers of DC presenting LACK peptides were found in the airways, but not in other compartments, for up to 8 weeks after antigen exposure. These LACK-presenting airway DC expressed CD11c and CD11b as well as high levels of surface molecules involved in uptake and costimulation. Taken together, our results may explain the chronic Th2 airway inflammation characteristic of allergic asthma.. in-vivo| airway hyperresponsiveness| immunological-tolerance| inhaled antigen| atopic asthma| murine model| lymph-nodes| expression| induction| lung.	FEB-2002	in-vivo| airway hyperresponsiveness| immunological-tolerance| inhaled antigen| atopic asthma| murine model| lymph-nodes| expression| induction| lung	Julia, V; Hessel, EM; Malherbe, L; Glaichenhaus, N; O'Garra, A; Coffman, RL	A restricted subset of dendritic cells captures airborne antigens and remains able to activate specific T cells long after antigen exposure		IMMUNITY		IN-VIVO; AIRWAY HYPERRESPONSIVENESS; IMMUNOLOGICAL-TOLERANCE; INHALED ANTIGEN; ATOPIC ASTHMA; MURINE MODEL; LYMPH-NODES; EXPRESSION; INDUCTION; LUNG	Mice sensitized for a Th2 response to Leishmania LACK antigen developed allergic airway inflammation upon exposure to LACK aerosol. Using multimers of I-A(d) molecules bound to a LACK peptide as probes, we tracked the migration of LACK-specific Th2 cells to the airways. Elevated numbers of LACK-specific Th2 cells remained in the airways for 5 weeks after the last aerosol. Substantial numbers of DC presenting LACK peptides were found in the airways, but not in other compartments, for up to 8 weeks after antigen exposure. These LACK-presenting airway DC expressed CD11c and CD11b as well as high levels of surface molecules involved in uptake and costimulation. Taken together, our results may explain the chronic Th2 airway inflammation characteristic of allergic asthma.	45	149	2002	13	10.1016/S1074-7613(02)00276-5	Immunology
Hypersensitivity pneumonitis: Current concepts and future questions. Hypersensitivity pneumonitis (extrinsic allergic alveolitis) caused by inhaled allergens can progress to disabling or even fatal end-stage lung disease. The only truly effective treatment is early recognition and control of exposure. Although patients produce antibody exuberantly, the immunopathogenesis involves cellular immunity-notably, CD8(+) cytotoxic lymphocytes, multinucleate giant cell granulomas, and ultimately interstitial fibrosis. Many causative agents have been recognized in occupational dusts or mists, but most current new cases arise from residential exposure to pet birds (pigeons and parakeets), contaminated humidifiers, and indoor molds. The symptoms and physical findings are nonspecific. Serum IgG containing high titers of specific antibody to the offending antigen is elevated, Pulmonary function tests show restrictive and diffusion defects with hypoxemia, especially after exercise. Occasionally, small airways disease causes obstruction. Radiographic changes vary according to the stage of the disease and are best evaluated by means of high-resolution computed tomography. In typical cases, the history of a known exposure and the presence of a characteristic interstitial lung disease with serologic confirmation of IgG antibody to the offending antigen suffice for diagnosis. In more obscure cases, observation of changes after a natural environmental exposure, bronchoalveolar lavage, and lung biopsy might be indicated. Among the many questions that remain are the following: What is the prevalence of hypersensitivity pneumonitis and how often is it the cause of chronic interstitial fibrosis? What is the long-term prognosis? Why do most individuals exposed to these antigens develop a vigorous antibody response whereas only a few develop the disease? How does exposure to endotoxin and cigarette smoking affect the disease? To answer these questions, standardized and validated clinical laboratory immunochemical tests are needed, in addition to a systematic approach to diagnosis, classification of disease severity, risk assessment, and management. This review is limited to the disease caused by airborne allergens and focuses on its immunopathogenesis, eliciting agents, clinical manifestations, diagnosis, management, and prognosis.. hypersensitivity pneumonitis| immunopathogenesis| lymphocytes| antibody| cytokines| chemokines| adhesion molecules| causative agents| diagnosis| prognosis| high-resolution computed tomography| bronchoalveolar lavage| pathology|extrinsic allergic alveolitis| bronchoalveolar lavage fluid| pigeon-breeders disease| immunological lung-disease| bird fanciers lung| mast-cell tryptase| high-resolution ct| acute farmers lung| pulmonary fibrosis| airway lesions.	NOV-2001	hypersensitivity pneumonitis| immunopathogenesis| lymphocytes| antibody| cytokines| chemokines| adhesion molecules| causative agents| diagnosis| prognosis| high-resolution computed tomography| bronchoalveolar lavage| pathology|extrinsic allergic alveolitis| bronchoalveolar lavage fluid| pigeon-breeders disease| immunological lung-disease| bird fanciers lung| mast-cell tryptase| high-resolution ct| acute farmers lung| pulmonary fibrosis| airway lesions	Patel, AM; Ryu, JH; Reed, CE	Hypersensitivity pneumonitis: Current concepts and future questions		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	hypersensitivity pneumonitis; immunopathogenesis; lymphocytes; antibody; cytokines; chemokines; adhesion molecules; causative agents; diagnosis; prognosis; high-resolution computed tomography; bronchoalveolar lavage; pathology	EXTRINSIC ALLERGIC ALVEOLITIS; BRONCHOALVEOLAR LAVAGE FLUID; PIGEON-BREEDERS DISEASE; IMMUNOLOGICAL LUNG-DISEASE; BIRD FANCIERS LUNG; MAST-CELL TRYPTASE; HIGH-RESOLUTION CT; ACUTE FARMERS LUNG; PULMONARY FIBROSIS; AIRWAY LESIONS	Hypersensitivity pneumonitis (extrinsic allergic alveolitis) caused by inhaled allergens can progress to disabling or even fatal end-stage lung disease. The only truly effective treatment is early recognition and control of exposure. Although patients produce antibody exuberantly, the immunopathogenesis involves cellular immunity-notably, CD8(+) cytotoxic lymphocytes, multinucleate giant cell granulomas, and ultimately interstitial fibrosis. Many causative agents have been recognized in occupational dusts or mists, but most current new cases arise from residential exposure to pet birds (pigeons and parakeets), contaminated humidifiers, and indoor molds. The symptoms and physical findings are nonspecific. Serum IgG containing high titers of specific antibody to the offending antigen is elevated, Pulmonary function tests show restrictive and diffusion defects with hypoxemia, especially after exercise. Occasionally, small airways disease causes obstruction. Radiographic changes vary according to the stage of the disease and are best evaluated by means of high-resolution computed tomography. In typical cases, the history of a known exposure and the presence of a characteristic interstitial lung disease with serologic confirmation of IgG antibody to the offending antigen suffice for diagnosis. In more obscure cases, observation of changes after a natural environmental exposure, bronchoalveolar lavage, and lung biopsy might be indicated. Among the many questions that remain are the following: What is the prevalence of hypersensitivity pneumonitis and how often is it the cause of chronic interstitial fibrosis? What is the long-term prognosis? Why do most individuals exposed to these antigens develop a vigorous antibody response whereas only a few develop the disease? How does exposure to endotoxin and cigarette smoking affect the disease? To answer these questions, standardized and validated clinical laboratory immunochemical tests are needed, in addition to a systematic approach to diagnosis, classification of disease severity, risk assessment, and management. This review is limited to the disease caused by airborne allergens and focuses on its immunopathogenesis, eliciting agents, clinical manifestations, diagnosis, management, and prognosis.	91	149	2001	10		Allergy; Immunology
A Summary of the Agency for Healthcare Research and Quality's Evidence Report on Breastfeeding in Developed Countries. Objectives: This article summarizes the Agency for Healthcare Research and Quality's evidence report on the effects of breastfeeding on term infant and maternal health outcomes in developed countries. Evidence Report Data Sources: Medline, CINAHL, Cochrane Library, bibliographies of selected reviews, and suggestions from domain experts were surveyed. Searches were limited to English-language publications. Evidence Report Review Methods: Eligible comparisons examined the association between differential exposure to breastfeeding and health outcomes. We assessed 15 infant and six maternal outcomes. For four outcomes, we also updated previously published systematic reviews. For the rest of the outcomes, we either summarized previous systematic reviews or conducted new systematic reviews; randomized and non-randomized comparative trials, prospective cohorts, and case-control studies were included. Adjusted estimates were extracted from non-experimental designs. The studies were graded for methodological quality. We did not draw conclusions from poor quality studies. Evidence Report Results: We screened over 9,000 abstracts. Thirty-two primary studies on term infant health outcomes, 43 primary studies on maternal health outcomes, and 28 systematic reviews or meta-analyses that covered approximately 400 individual studies were included in this review. A history of breastfeeding was associated with a reduction in the risk of acute otitis media, nonspecific gastroenteritis, severe lower respiratory tract infections, atopic dermatitis, asthma (young children), obesity, type 1 and 2 diabetes, childhood leukemia, and sudden infant death syndrome. There was no relationship between breastfeeding in term infants and cognitive performance. There were insufficient good quality data to address the relationship between breastfeeding and cardiovascular diseases and infant mortality. For maternal outcomes, a history of lactation was associated with a reduced risk of type 2 diabetes, breast, and ovarian cancer. Early cessation of breastfeeding or no breastfeeding was associated with an increased risk of maternal postpartum depression. There was no relationship between a history of lactation and the risk of osteoporosis. The effect of breastfeeding in mothers on return-to-prepregnancy weight was negligible, and the effect of breastfeeding on postpartum weight loss was unclear. Evidence Report Conclusions: A history of breastfeeding is associated with a reduced risk of many diseases in infants and mothers. Future research would benefit from clearer selection criteria, definitions of breastfeeding exposure, and adjustment for potential confounders. Matched designs such as sibling analysis may provide a method to control for hereditary and household factors that are important in certain outcomes.. epithelial ovarian-cancer| infant-death-syndrome| environmental risk-factors| prospective birth cohort| acute otitis-media| cognitive-development| diabetes-mellitus| reproductive factors| childhood leukemia| hip fracture.	OCT-2009	epithelial ovarian-cancer| infant-death-syndrome| environmental risk-factors| prospective birth cohort| acute otitis-media| cognitive-development| diabetes-mellitus| reproductive factors| childhood leukemia| hip fracture	Ip, S; Chung, M; Raman, G; Trikalinos, TA; Lau, J	A Summary of the Agency for Healthcare Research and Quality's Evidence Report on Breastfeeding in Developed Countries		BREASTFEEDING MEDICINE		EPITHELIAL OVARIAN-CANCER; INFANT-DEATH-SYNDROME; ENVIRONMENTAL RISK-FACTORS; PROSPECTIVE BIRTH COHORT; ACUTE OTITIS-MEDIA; COGNITIVE-DEVELOPMENT; DIABETES-MELLITUS; REPRODUCTIVE FACTORS; CHILDHOOD LEUKEMIA; HIP FRACTURE	Objectives: This article summarizes the Agency for Healthcare Research and Quality's evidence report on the effects of breastfeeding on term infant and maternal health outcomes in developed countries. Evidence Report Data Sources: Medline, CINAHL, Cochrane Library, bibliographies of selected reviews, and suggestions from domain experts were surveyed. Searches were limited to English-language publications. Evidence Report Review Methods: Eligible comparisons examined the association between differential exposure to breastfeeding and health outcomes. We assessed 15 infant and six maternal outcomes. For four outcomes, we also updated previously published systematic reviews. For the rest of the outcomes, we either summarized previous systematic reviews or conducted new systematic reviews; randomized and non-randomized comparative trials, prospective cohorts, and case-control studies were included. Adjusted estimates were extracted from non-experimental designs. The studies were graded for methodological quality. We did not draw conclusions from poor quality studies. Evidence Report Results: We screened over 9,000 abstracts. Thirty-two primary studies on term infant health outcomes, 43 primary studies on maternal health outcomes, and 28 systematic reviews or meta-analyses that covered approximately 400 individual studies were included in this review. A history of breastfeeding was associated with a reduction in the risk of acute otitis media, nonspecific gastroenteritis, severe lower respiratory tract infections, atopic dermatitis, asthma (young children), obesity, type 1 and 2 diabetes, childhood leukemia, and sudden infant death syndrome. There was no relationship between breastfeeding in term infants and cognitive performance. There were insufficient good quality data to address the relationship between breastfeeding and cardiovascular diseases and infant mortality. For maternal outcomes, a history of lactation was associated with a reduced risk of type 2 diabetes, breast, and ovarian cancer. Early cessation of breastfeeding or no breastfeeding was associated with an increased risk of maternal postpartum depression. There was no relationship between a history of lactation and the risk of osteoporosis. The effect of breastfeeding in mothers on return-to-prepregnancy weight was negligible, and the effect of breastfeeding on postpartum weight loss was unclear. Evidence Report Conclusions: A history of breastfeeding is associated with a reduced risk of many diseases in infants and mothers. Future research would benefit from clearer selection criteria, definitions of breastfeeding exposure, and adjustment for potential confounders. Matched designs such as sibling analysis may provide a method to control for hereditary and household factors that are important in certain outcomes.	119	148	2009	14	10.1089/bfm.2009.0050	Obstetrics & Gynecology; Pediatrics
Traffic-related air pollution and asthma onset in children: A prospective cohort study with individual exposure measurement. BACKGROUND: The question of whether air pollution contributes to asthma onset remains unresolved. OBJECTIVES: In this study, we assessed the association between asthma onset in children and traffic-related air pollution. METHODS: We selected a sample of 217 children from participants in the Southern California Children's Health Study, a prospective cohort designed to investigate associations between air pollution and respiratory health in children 10-18 years of age. Individual covariates and new asthma incidence (30 cases) were reported annually through questionnaires during 8 years of follow-up. Children had nitrogen dioxide monitors placed outside their home for 2 weeks in the summer and 2 weeks in the fall-winter season as a marker of traffic-related air pollution. We used multilevel Cox models to test the associations between asthma and air pollution. RESULTS: In models controlling for confounders, incident asthma was positively associated with traffic Pollution, with a hazard ratio (HR) of 1.29 [95% confidence interval (CI), 1.07-1.56] across the average within-community interquartille range of 6.2 ppb in annual residential NO(2). Using the total interquartile range for all measurements of 28.9 ppb increased the HR to 3.25 (95% CI, 1.35-7.85). CONCLUSIONS: In this cohort, markers of traffic-related air pollution were associated with the onset of asthma. The risks observed suggest that air pollution exposure contributes to new-onset asthma.. air pollution| asthma onset| children| nitrogen dioxide| traffic|chronic respiratory symptoms| childhood asthma| allergic rhinitis| school children| prevalence| health| questionnaire| community| age| epidemiology.	OCT-2008	air pollution| asthma onset| children| nitrogen dioxide| traffic|chronic respiratory symptoms| childhood asthma| allergic rhinitis| school children| prevalence| health| questionnaire| community| age| epidemiology	Jerrett, M; Shankardas, K; Berhane, K; Gauderman, WJ; Kunzli, N; Avol, E; Gilliland, F; Lurmann, F; Molitor, JN; Molitor, JT; Thomas, DC; Peters, J; McConnell, R	Traffic-related air pollution and asthma onset in children: A prospective cohort study with individual exposure measurement		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma onset; children; nitrogen dioxide; traffic	CHRONIC RESPIRATORY SYMPTOMS; CHILDHOOD ASTHMA; ALLERGIC RHINITIS; SCHOOL CHILDREN; PREVALENCE; HEALTH; QUESTIONNAIRE; COMMUNITY; AGE; EPIDEMIOLOGY	BACKGROUND: The question of whether air pollution contributes to asthma onset remains unresolved. OBJECTIVES: In this study, we assessed the association between asthma onset in children and traffic-related air pollution. METHODS: We selected a sample of 217 children from participants in the Southern California Children's Health Study, a prospective cohort designed to investigate associations between air pollution and respiratory health in children 10-18 years of age. Individual covariates and new asthma incidence (30 cases) were reported annually through questionnaires during 8 years of follow-up. Children had nitrogen dioxide monitors placed outside their home for 2 weeks in the summer and 2 weeks in the fall-winter season as a marker of traffic-related air pollution. We used multilevel Cox models to test the associations between asthma and air pollution. RESULTS: In models controlling for confounders, incident asthma was positively associated with traffic Pollution, with a hazard ratio (HR) of 1.29 [95% confidence interval (CI), 1.07-1.56] across the average within-community interquartille range of 6.2 ppb in annual residential NO(2). Using the total interquartile range for all measurements of 28.9 ppb increased the HR to 3.25 (95% CI, 1.35-7.85). CONCLUSIONS: In this cohort, markers of traffic-related air pollution were associated with the onset of asthma. The risks observed suggest that air pollution exposure contributes to new-onset asthma.	53	148	2008	6	10.1289/ehp.10968	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Fish consumption during the first year of life and development of allergic diseases during childhood. Background: Fish consumption during infancy has been regarded as a risk factor for allergic disease but later evidence suggests a protective role. However, methodological limitations in the studies make conclusions uncertain. The aim of this study was to assess the association between fish consumption during the first year of life and development of allergic diseases by age 4. Methods: A prospective birth cohort of 4089 new-born infants was followed for 4 years using parental questionnaires at ages 2 months, 1, 2 and 4 years to collect information on exposure and health effects. The response rate at 4 years was 90%. A clinical investigation was performed at age 4 years, which included blood sampling for analysis of specific IgE to common food and airborne allergens. Results: Parental allergic disease and onset of eczema or wheeze during the first year of life delayed introduction of fish in the child's diet. After exclusion of such children to avoid disease-related modification of exposure, regular fish consumption during the first year of life was associated with a reduced risk for allergic disease by age 4, ORadj 0.76 (95% CI 0.61-0.94) and sensitization, ORadj 0.76 (0.58-1.0). The reduced risk appeared most pronounced for multiple disease, ORadj 0.56 (0.35-0.89). IgE-sensitization to fish was only present among 18 of the 2614 children. Conclusion: Regular fish consumption before age 1 appears to be associated with a reduced risk of allergic disease and sensitization to food and inhalant allergens during the first 4 years of life.. asthma| bamse| children| fish| sensitization|oil supplementation| birth cohort| fatty-acids| food allergy| asthma risk| children| atopy| infants| omega-3-fatty-acids| prevention.	AUG-2006	asthma| bamse| children| fish| sensitization|oil supplementation| birth cohort| fatty-acids| food allergy| asthma risk| children| atopy| infants| omega-3-fatty-acids| prevention	Kull, I; Bergstrom, A; Lilja, G; Pershagen, G; Wickman, M	Fish consumption during the first year of life and development of allergic diseases during childhood		ALLERGY	asthma; BAMSE; children; fish; sensitization	OIL SUPPLEMENTATION; BIRTH COHORT; FATTY-ACIDS; FOOD ALLERGY; ASTHMA RISK; CHILDREN; ATOPY; INFANTS; OMEGA-3-FATTY-ACIDS; PREVENTION	Background: Fish consumption during infancy has been regarded as a risk factor for allergic disease but later evidence suggests a protective role. However, methodological limitations in the studies make conclusions uncertain. The aim of this study was to assess the association between fish consumption during the first year of life and development of allergic diseases by age 4. Methods: A prospective birth cohort of 4089 new-born infants was followed for 4 years using parental questionnaires at ages 2 months, 1, 2 and 4 years to collect information on exposure and health effects. The response rate at 4 years was 90%. A clinical investigation was performed at age 4 years, which included blood sampling for analysis of specific IgE to common food and airborne allergens. Results: Parental allergic disease and onset of eczema or wheeze during the first year of life delayed introduction of fish in the child's diet. After exclusion of such children to avoid disease-related modification of exposure, regular fish consumption during the first year of life was associated with a reduced risk for allergic disease by age 4, ORadj 0.76 (95% CI 0.61-0.94) and sensitization, ORadj 0.76 (0.58-1.0). The reduced risk appeared most pronounced for multiple disease, ORadj 0.56 (0.35-0.89). IgE-sensitization to fish was only present among 18 of the 2614 children. Conclusion: Regular fish consumption before age 1 appears to be associated with a reduced risk of allergic disease and sensitization to food and inhalant allergens during the first 4 years of life.	31	148	2006	7	10.1111/j.1398-9995.2006.01115.x	Allergy; Immunology
Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells. Respiratory syncytial virus (RSV) preferentially infects airway epithelial cells, causing bronchiolitis, upper respiratory infections, asthma exacerbations, chronic obstructive pulmonary disease exacerbations, and pneumonia in immunocompromised hosts. A replication intermediate of RSV is dsRNA. This is an important ligand for both the innate immune receptor, TLR3, and protein kinase R (PKR). One known effect of RSV infection is the increased responsiveness of airway epithelial cells to subsequent bacterial ligands (i.e., LPS). In this study, we examined a possible role for RSV infection in increasing amounts and responsiveness of another TLR, TLR3. These studies demonstrate that RSV infection of A549 and human tracheobronchial epithelial cells increases the amounts of TLR3 and PKR in a time-dependent manner. This leads to increased NF-kappa B activity and production of the inflammatory cytokine IL-8 following a later exposure to dsRNA. Importantly, TLR3 was not detected on the cell surface at baseline but was detected on the cell surface after RSV infection. The data demonstrate that RSV, via an effect on TLR3 and PKR, sensitizes airway epithelial cells to subsequent dsRNA exposure. These findings are consistent with the hypothesis that RSV infection sensitizes the airway epithelium to subsequent viral and bacterial exposures by up-regulating TLRs and increasing their membrane localization.. nf-kappa-b| toll-like receptor-3| dendritic cells| activation| pkr| expression| localization| trafficking| recognition| cytokines.	FEB 1-2006	nf-kappa-b| toll-like receptor-3| dendritic cells| activation| pkr| expression| localization| trafficking| recognition| cytokines	Groskreutz, DJ; Monick, MM; Powers, LS; Yarovinsky, TO; Look, DC; Hunninghake, GW	Respiratory syncytial virus induces TLR3 protein and protein kinase R, leading to increased double-stranded RNA responsiveness in airway epithelial cells		JOURNAL OF IMMUNOLOGY		NF-KAPPA-B; TOLL-LIKE RECEPTOR-3; DENDRITIC CELLS; ACTIVATION; PKR; EXPRESSION; LOCALIZATION; TRAFFICKING; RECOGNITION; CYTOKINES	Respiratory syncytial virus (RSV) preferentially infects airway epithelial cells, causing bronchiolitis, upper respiratory infections, asthma exacerbations, chronic obstructive pulmonary disease exacerbations, and pneumonia in immunocompromised hosts. A replication intermediate of RSV is dsRNA. This is an important ligand for both the innate immune receptor, TLR3, and protein kinase R (PKR). One known effect of RSV infection is the increased responsiveness of airway epithelial cells to subsequent bacterial ligands (i.e., LPS). In this study, we examined a possible role for RSV infection in increasing amounts and responsiveness of another TLR, TLR3. These studies demonstrate that RSV infection of A549 and human tracheobronchial epithelial cells increases the amounts of TLR3 and PKR in a time-dependent manner. This leads to increased NF-kappa B activity and production of the inflammatory cytokine IL-8 following a later exposure to dsRNA. Importantly, TLR3 was not detected on the cell surface at baseline but was detected on the cell surface after RSV infection. The data demonstrate that RSV, via an effect on TLR3 and PKR, sensitizes airway epithelial cells to subsequent dsRNA exposure. These findings are consistent with the hypothesis that RSV infection sensitizes the airway epithelium to subsequent viral and bacterial exposures by up-regulating TLRs and increasing their membrane localization.	37	148	2006	8		Immunology
"Systematic assessment of difficult-to-treat asthma. Five per cent of asthmatics remain symptomatic despite high-dose treatment. The aim of the study was to investigate how often such difficult-to-treat asthma is due to intractable asthma, misdiagnosis, non-adherence with therapy, or psychiatric problems. Difficult asthma was defined as persistence of symptoms despite treatment at step 4 of British guidelines or requirement for long-term oral glucocorticoids (step 5). One-hundred patients with a respiratory physician diagnosis of asthma were investigated in a single tertiary respiratory unit in an open and descriptive study. Twelve of the patients studied did not have asthma and a further seven had additional diagnoses. Of the remainder, 55 had an asthma diagnosis confirmed by demonstration of reversible airflow narrowing or peak flow variability, whilst 20 did not. Noncompliance with prednisolone therapy was more frequent in the 55 with confirmed asthma (nine of 18 prescribed oral prednisolone at a dose of greater than or equal to 15 mg(.)day(-1)) and was not detected in the ""unconfirmed asthma"" group. There were no other significant differences between these groups. A major psychiatric component was detected in 10 patients. Systematic evaluation of difficult asthma is useful as it can identify alternative or additional diagnoses, psychiatric illness or nonconcordance with therapy in a substantial proportion of cases (32% in the present series).. adherence| diagnosis| psychiatry| severe asthma|air-flow limitation| clinical characteristics| resistant asthma| brittle asthma| management| trial."	SEP-2003	adherence| diagnosis| psychiatry| severe asthma|air-flow limitation| clinical characteristics| resistant asthma| brittle asthma| management| trial	Robinson, DS; Campbell, DA; Durharm, SR; Pfeffer, J; Barnes, PJ; Chung, KF	Systematic assessment of difficult-to-treat asthma		EUROPEAN RESPIRATORY JOURNAL	adherence; diagnosis; psychiatry; severe asthma	AIR-FLOW LIMITATION; CLINICAL CHARACTERISTICS; RESISTANT ASTHMA; BRITTLE ASTHMA; MANAGEMENT; TRIAL	"Five per cent of asthmatics remain symptomatic despite high-dose treatment. The aim of the study was to investigate how often such difficult-to-treat asthma is due to intractable asthma, misdiagnosis, non-adherence with therapy, or psychiatric problems. Difficult asthma was defined as persistence of symptoms despite treatment at step 4 of British guidelines or requirement for long-term oral glucocorticoids (step 5). One-hundred patients with a respiratory physician diagnosis of asthma were investigated in a single tertiary respiratory unit in an open and descriptive study. Twelve of the patients studied did not have asthma and a further seven had additional diagnoses. Of the remainder, 55 had an asthma diagnosis confirmed by demonstration of reversible airflow narrowing or peak flow variability, whilst 20 did not. Noncompliance with prednisolone therapy was more frequent in the 55 with confirmed asthma (nine of 18 prescribed oral prednisolone at a dose of greater than or equal to 15 mg(.)day(-1)) and was not detected in the ""unconfirmed asthma"" group. There were no other significant differences between these groups. A major psychiatric component was detected in 10 patients. Systematic evaluation of difficult asthma is useful as it can identify alternative or additional diagnoses, psychiatric illness or nonconcordance with therapy in a substantial proportion of cases (32% in the present series)."	23	148	2003	6	10.1183/09031936.03.00017003	Respiratory System
Clinical aspects of exhaled nitric oxide. There has been intense research into the role nitric oxide (NO) plays in physiological and pathological mechanisms and its clinical significance in respiratory medicine, Elevated levels of exhaled levels of exhaled NO in asthma and other inflammatory lung diseases lead to many studies examining NO as potential markers of airway inflammation, enabling repeated noninvasive and standardized monitoring of airway inflammation. In airway inflammation, NO is not merely a marker but may have antiinflammatory and pro-inflammatory effects, Significant correlation has been found between exhaled NO and skin test scores in steroid naive asthmatic patients, allowing to discriminate patients with and without airway responsiveness. Exhaled NO is significantly elevated in acute asthma, or steroid-resistant severe asthma, or when the maintenance dose of inhaled steroids is reduced, and quickly reduced down to the levels in patients with stable asthma after steroid treatment. Exhaled NO has been successfully used to monitor anti-inflammatory treatment with inhaled corticosteroids in asthma, Exhaled NO is extremely sensitive and rapid marker of the dose-dependent effect of steroid treatment, or asthma deterioration, which is increased to any changes in lung function, provocative concentration causing a 20% fall in forced expiratory volume, sputum eosinophilia or asthma symptoms. Exhaled NO is not increased in stable chronic obstructive pulmonary disease (COPD), but patients with unstable COPD, or bronchiectasis have high NO levels. Exhaled and nasal NO are diagnostically low in cystic fibrosis and primary pulmonary dyskinesia. Analysis of exhaled air, including nitric oxide, is feasible and could provide a noninvasive method for use in monitoring and management of lung diseases.. asthma| exhaled breath| isoprostanes| nitric oxide| noninvasive markers of airway| inflammation| s-nitrosothiols|obstructive pulmonary-disease| lung-transplant recipients| cystic-fibrosis| asthmatic-patients| mild asthma| induced sputum| airway inflammation| oxidative stress| young-children| obliterative bronchiolitis.	OCT-2000	asthma| exhaled breath| isoprostanes| nitric oxide| noninvasive markers of airway| inflammation| s-nitrosothiols|obstructive pulmonary-disease| lung-transplant recipients| cystic-fibrosis| asthmatic-patients| mild asthma| induced sputum| airway inflammation| oxidative stress| young-children| obliterative bronchiolitis	Kharitonov, SA; Barnes, PJ	Clinical aspects of exhaled nitric oxide		EUROPEAN RESPIRATORY JOURNAL	asthma; exhaled breath; isoprostanes; nitric oxide; noninvasive markers of airway; inflammation; S-nitrosothiols	OBSTRUCTIVE PULMONARY-DISEASE; LUNG-TRANSPLANT RECIPIENTS; CYSTIC-FIBROSIS; ASTHMATIC-PATIENTS; MILD ASTHMA; INDUCED SPUTUM; AIRWAY INFLAMMATION; OXIDATIVE STRESS; YOUNG-CHILDREN; OBLITERATIVE BRONCHIOLITIS	There has been intense research into the role nitric oxide (NO) plays in physiological and pathological mechanisms and its clinical significance in respiratory medicine, Elevated levels of exhaled levels of exhaled NO in asthma and other inflammatory lung diseases lead to many studies examining NO as potential markers of airway inflammation, enabling repeated noninvasive and standardized monitoring of airway inflammation. In airway inflammation, NO is not merely a marker but may have antiinflammatory and pro-inflammatory effects, Significant correlation has been found between exhaled NO and skin test scores in steroid naive asthmatic patients, allowing to discriminate patients with and without airway responsiveness. Exhaled NO is significantly elevated in acute asthma, or steroid-resistant severe asthma, or when the maintenance dose of inhaled steroids is reduced, and quickly reduced down to the levels in patients with stable asthma after steroid treatment. Exhaled NO has been successfully used to monitor anti-inflammatory treatment with inhaled corticosteroids in asthma, Exhaled NO is extremely sensitive and rapid marker of the dose-dependent effect of steroid treatment, or asthma deterioration, which is increased to any changes in lung function, provocative concentration causing a 20% fall in forced expiratory volume, sputum eosinophilia or asthma symptoms. Exhaled NO is not increased in stable chronic obstructive pulmonary disease (COPD), but patients with unstable COPD, or bronchiectasis have high NO levels. Exhaled and nasal NO are diagnostically low in cystic fibrosis and primary pulmonary dyskinesia. Analysis of exhaled air, including nitric oxide, is feasible and could provide a noninvasive method for use in monitoring and management of lung diseases.	140	148	2000	12	10.1183/09031936.00.16478100	Respiratory System
Health and productivity gains from better indoor environments and their relationship with building energy efficiency. Theoretical considerations and empirical data suggest that existing technologies and procedures can improve indoor environments in a manner that significantly increases productivity and health. The existing literature contains moderate to strong evidence that characteristics of buildings and indoor environments significantly influence rates of communicable respiratory illness, allergy and asthma symptoms, sick building symptoms, and worker performance. Whereas there is considerable uncertainty in the estimates of the magnitudes of productivity gains that may be obtained by providing better indoor environments, the projected gains are very large. For the United States, the estimated potential annual savings and productivity gains are $6 to $14 billion from reduced respiratory disease, $1 to $4 billion from reduced allergies and asthma, $10 to $30 billion from reduced sick building syndrome symptoms, and $20 to $160 billion from direct improvements in worker performance that are unrelated to health. Productivity gains that are quantified and demonstrated could serve as a strong stimulus for energy efficiency measures that simultaneously improve the indoor environment.. economics| health| productivity|respiratory-tract infections| office workers| united-states| task-performance| allergic disease| economic costs| asthma| children| symptoms| satisfaction.	2000	economics| health| productivity|respiratory-tract infections| office workers| united-states| task-performance| allergic disease| economic costs| asthma| children| symptoms| satisfaction	Fisk, WJ	Health and productivity gains from better indoor environments and their relationship with building energy efficiency		ANNUAL REVIEW OF ENERGY AND THE ENVIRONMENT	economics; health; productivity	RESPIRATORY-TRACT INFECTIONS; OFFICE WORKERS; UNITED-STATES; TASK-PERFORMANCE; ALLERGIC DISEASE; ECONOMIC COSTS; ASTHMA; CHILDREN; SYMPTOMS; SATISFACTION	Theoretical considerations and empirical data suggest that existing technologies and procedures can improve indoor environments in a manner that significantly increases productivity and health. The existing literature contains moderate to strong evidence that characteristics of buildings and indoor environments significantly influence rates of communicable respiratory illness, allergy and asthma symptoms, sick building symptoms, and worker performance. Whereas there is considerable uncertainty in the estimates of the magnitudes of productivity gains that may be obtained by providing better indoor environments, the projected gains are very large. For the United States, the estimated potential annual savings and productivity gains are $6 to $14 billion from reduced respiratory disease, $1 to $4 billion from reduced allergies and asthma, $10 to $30 billion from reduced sick building syndrome symptoms, and $20 to $160 billion from direct improvements in worker performance that are unrelated to health. Productivity gains that are quantified and demonstrated could serve as a strong stimulus for energy efficiency measures that simultaneously improve the indoor environment.	84	148	2000	30	10.1146/annurev.energy.25.1.537	Energy & Fuels; Engineering
Interleukin-1 alpha controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33. House dust mite (HDM) is one of the most common allergens worldwide. In this study, we have addressed the involvement of IL-1 in the interaction between HDM and the innate immune response driven by lung epithelial cells (ECs) and dendritic cells (DCs) that leads to asthma. Mice lacking IL-1R on radioresistant cells, but not hematopoietic cells, failed to mount a Th2 immune response and did not develop asthma to HDM. Experiments performed in vivo and in isolated air-liquid interface cultures of bronchial ECs showed that TLR4 signals induced the release of IL-1 alpha, which then acted in an autocrine manner to trigger the release of DC-attracting chemokines, GM-CSF, and IL-33. Consequently, allergic sensitization to HDM was abolished in vivo when IL-1 alpha, GM-CSF, or IL-33 was neutralized. Thymic stromal lymphopoietin (TSLP) became important only when high doses of allergen were administered. These findings put IL-1 alpha upstream in the cytokine cascade leading to epithelial and DC activation in response to inhaled HDM allergen.. thymic stromal lymphopoietin| adaptive immune-responses| dendritic cell maturation| nf-kappa-b| t-cells| airway inflammation| th2 responses| severe asthma| in-vivo| mice.	JUL 30-2012	thymic stromal lymphopoietin| adaptive immune-responses| dendritic cell maturation| nf-kappa-b| t-cells| airway inflammation| th2 responses| severe asthma| in-vivo| mice	Willart, MAM; Deswarte, K; Pouliot, P; Braun, H; Beyaert, R; Lambrecht, BN; Hammad, H	Interleukin-1 alpha controls allergic sensitization to inhaled house dust mite via the epithelial release of GM-CSF and IL-33		JOURNAL OF EXPERIMENTAL MEDICINE		THYMIC STROMAL LYMPHOPOIETIN; ADAPTIVE IMMUNE-RESPONSES; DENDRITIC CELL MATURATION; NF-KAPPA-B; T-CELLS; AIRWAY INFLAMMATION; TH2 RESPONSES; SEVERE ASTHMA; IN-VIVO; MICE	House dust mite (HDM) is one of the most common allergens worldwide. In this study, we have addressed the involvement of IL-1 in the interaction between HDM and the innate immune response driven by lung epithelial cells (ECs) and dendritic cells (DCs) that leads to asthma. Mice lacking IL-1R on radioresistant cells, but not hematopoietic cells, failed to mount a Th2 immune response and did not develop asthma to HDM. Experiments performed in vivo and in isolated air-liquid interface cultures of bronchial ECs showed that TLR4 signals induced the release of IL-1 alpha, which then acted in an autocrine manner to trigger the release of DC-attracting chemokines, GM-CSF, and IL-33. Consequently, allergic sensitization to HDM was abolished in vivo when IL-1 alpha, GM-CSF, or IL-33 was neutralized. Thymic stromal lymphopoietin (TSLP) became important only when high doses of allergen were administered. These findings put IL-1 alpha upstream in the cytokine cascade leading to epithelial and DC activation in response to inhaled HDM allergen.	52	147	2012	13	10.1084/jem.20112691	Immunology; Research & Experimental Medicine
Smoke-free Legislation and Hospitalizations for Childhood Asthma.. Background: Previous studies have shown that after the adoption of comprehensive smoke-free legislation, there is a reduction in respiratory symptoms among workers in bars. However, it is not known whether respiratory disease is also reduced among people who do not have occupational exposure to environmental tobacco smoke. The aim of our study was to determine whether the ban on smoking in public places in Scotland, which was initiated in March 2006, influenced the rate of hospital admissions for childhood asthma. Methods: Routine hospital administrative data were used to identify all hospital admissions for asthma in Scotland from January 2000 through October 2009 among children younger than 15 years of age. A negative binomial regression model was fitted, with adjustment for age group, sex, quintile of socioeconomic status, urban or rural residence, month, and year. Tests for interactions were also performed. Results: Before the legislation was implemented, admissions for asthma were increasing at a mean rate of 5.2% per year (95% confidence interval [CI], 3.9 to 6.6). After implementation of the legislation, there was a mean reduction in the rate of admissions of 18.2% per year relative to the rate on March 26, 2006 (95% CI, 14.7 to 21.8; P<0.001). The reduction was apparent among both preschool and school-age children. There were no significant interactions between hospital admissions for asthma and age group, sex, urban or rural residence, region, or quintile of socioeconomic status. Conclusions: In Scotland, passage of smoke-free legislation in 2006 was associated with a subsequent reduction in the rate of respiratory disease in populations other than those with occupational exposure to environmental tobacco smoke. (Funded by NHS Health Scotland.) N Engl J Med 2010;363:1139-45.. environmental tobacco-smoke| cross-sectional survey| secondhand smoke| 2nd-hand smoke| exposure| scotland| implementation| children| health.	SEP 16-2010	environmental tobacco-smoke| cross-sectional survey| secondhand smoke| 2nd-hand smoke| exposure| scotland| implementation| children| health	Mackay, D; Haw, S; Ayres, JG; Fischbacher, C; Pell, JP	Smoke-free Legislation and Hospitalizations for Childhood Asthma.		NEW ENGLAND JOURNAL OF MEDICINE		ENVIRONMENTAL TOBACCO-SMOKE; CROSS-SECTIONAL SURVEY; SECONDHAND SMOKE; 2ND-HAND SMOKE; EXPOSURE; SCOTLAND; IMPLEMENTATION; CHILDREN; HEALTH	Background: Previous studies have shown that after the adoption of comprehensive smoke-free legislation, there is a reduction in respiratory symptoms among workers in bars. However, it is not known whether respiratory disease is also reduced among people who do not have occupational exposure to environmental tobacco smoke. The aim of our study was to determine whether the ban on smoking in public places in Scotland, which was initiated in March 2006, influenced the rate of hospital admissions for childhood asthma. Methods: Routine hospital administrative data were used to identify all hospital admissions for asthma in Scotland from January 2000 through October 2009 among children younger than 15 years of age. A negative binomial regression model was fitted, with adjustment for age group, sex, quintile of socioeconomic status, urban or rural residence, month, and year. Tests for interactions were also performed. Results: Before the legislation was implemented, admissions for asthma were increasing at a mean rate of 5.2% per year (95% confidence interval [CI], 3.9 to 6.6). After implementation of the legislation, there was a mean reduction in the rate of admissions of 18.2% per year relative to the rate on March 26, 2006 (95% CI, 14.7 to 21.8; P<0.001). The reduction was apparent among both preschool and school-age children. There were no significant interactions between hospital admissions for asthma and age group, sex, urban or rural residence, region, or quintile of socioeconomic status. Conclusions: In Scotland, passage of smoke-free legislation in 2006 was associated with a subsequent reduction in the rate of respiratory disease in populations other than those with occupational exposure to environmental tobacco smoke. (Funded by NHS Health Scotland.) N Engl J Med 2010;363:1139-45.	20	147	2010	7	10.1056/NEJMoa1002861	General & Internal Medicine
Induction of Epithelial-Mesenchymal Transition in Primary Airway Epithelial Cells from Patients with Asthma by Transforming Growth Factor-beta 1. Rationale Airway remodeling in asthma is associated with the accumulation of fibroblasts, the primary cell responsible for synthesis and secretion of extracellular matrix proteins. The process by which the number of fibroblasts increases in asthma is poorly understood, but epithelial-mesenchymal transition (EMT) may play a significant role. Objectives: To evaluate whether EMT occurs in primary airway epithelial cells (AECs), the mechanisms involved, and if this process is altered in asthmatic AECs. Methods: AECs were obtained from subjects with asthma (n = 8) and normal subjects without asthma (n = 10). Monolayer and air-liquid interface-AEC (ALI-AEC) cultures were treated with transforming growth factor (TGF)-beta 1 (10 ng/ml) for 72 hours and assayed for mesenchymal and epithelial markers using quantitative polymerase chain reaction, confocal microscopy, and immunoblot. The involvement of BMP-7, Smad3, and MAPK-mediated signaling were also evaluated. Measurements and Main Results: TGF-beta 1-induced EMT in AEC monolayers derived from subjects with asthma and normal donors. EMT was characterized by changes in cell morphology, increased expression of mesenchymal markers EDA-fibronectin, vimentin, alpha-smooth muscle actin, and collagen-1, and loss of epithelial markers E-cadherin and zonular occludin-1. Inhibition of TGF-beta 1-induced signaling with Smad3-inhibiting siRNA or TGF-beta 1-neutralizing antibodies prevented and reversed EMT, respectively, whereas BMP-7 had no effect. In ALI-AEC cultures derived from normal subjects, EMT was confined to basally situated cells, whereas in asthmatic ALI-AEC cultures EMT was widespread throughout the epithelium. Conclusions: TGF-beta 1 induces EMT in a Smad3-dependent manner in primary AECs. However, in asthmatic-derived ALI-AEC cultures, the number of cells undergoing EMT is greater. These findings support the hypothesis that epithelial repair in asthmatic airways is dysregulated.. asthma| epithelial-mesenchymal transition| transforming growth factor-beta 1| epithelium|growth-factor-beta| reticular basement-membrane| activated protein-kinase| pulmonary-fibrosis| expression| mouse| lung| smad| transdifferentiation| tgf-beta-1.	JUL 15-2009	asthma| epithelial-mesenchymal transition| transforming growth factor-beta 1| epithelium|growth-factor-beta| reticular basement-membrane| activated protein-kinase| pulmonary-fibrosis| expression| mouse| lung| smad| transdifferentiation| tgf-beta-1	Hackett, TL; Warner, SM; Stefanowicz, D; Shaheen, F; Pechkovsky, DV; Murray, LA; Argentieri, R; Kicic, A; Stick, SM; Bai, TR; Knight, DA	Induction of Epithelial-Mesenchymal Transition in Primary Airway Epithelial Cells from Patients with Asthma by Transforming Growth Factor-beta 1		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; epithelial-mesenchymal transition; transforming growth factor-beta 1; epithelium	GROWTH-FACTOR-BETA; RETICULAR BASEMENT-MEMBRANE; ACTIVATED PROTEIN-KINASE; PULMONARY-FIBROSIS; EXPRESSION; MOUSE; LUNG; SMAD; TRANSDIFFERENTIATION; TGF-BETA-1	Rationale Airway remodeling in asthma is associated with the accumulation of fibroblasts, the primary cell responsible for synthesis and secretion of extracellular matrix proteins. The process by which the number of fibroblasts increases in asthma is poorly understood, but epithelial-mesenchymal transition (EMT) may play a significant role. Objectives: To evaluate whether EMT occurs in primary airway epithelial cells (AECs), the mechanisms involved, and if this process is altered in asthmatic AECs. Methods: AECs were obtained from subjects with asthma (n = 8) and normal subjects without asthma (n = 10). Monolayer and air-liquid interface-AEC (ALI-AEC) cultures were treated with transforming growth factor (TGF)-beta 1 (10 ng/ml) for 72 hours and assayed for mesenchymal and epithelial markers using quantitative polymerase chain reaction, confocal microscopy, and immunoblot. The involvement of BMP-7, Smad3, and MAPK-mediated signaling were also evaluated. Measurements and Main Results: TGF-beta 1-induced EMT in AEC monolayers derived from subjects with asthma and normal donors. EMT was characterized by changes in cell morphology, increased expression of mesenchymal markers EDA-fibronectin, vimentin, alpha-smooth muscle actin, and collagen-1, and loss of epithelial markers E-cadherin and zonular occludin-1. Inhibition of TGF-beta 1-induced signaling with Smad3-inhibiting siRNA or TGF-beta 1-neutralizing antibodies prevented and reversed EMT, respectively, whereas BMP-7 had no effect. In ALI-AEC cultures derived from normal subjects, EMT was confined to basally situated cells, whereas in asthmatic ALI-AEC cultures EMT was widespread throughout the epithelium. Conclusions: TGF-beta 1 induces EMT in a Smad3-dependent manner in primary AECs. However, in asthmatic-derived ALI-AEC cultures, the number of cells undergoing EMT is greater. These findings support the hypothesis that epithelial repair in asthmatic airways is dysregulated.	57	147	2009	12	10.1164/rccm.200811-1730OC	General & Internal Medicine; Respiratory System
Gene-Environment Interaction in Genome-Wide Association Studies. It is a commonly held belief that most complex diseases (e.g., diabetes, asthma, cancer) are affected in part by interactions between genes and environmental factors. However, investigators conducting genome-wide association studies typically test for only the marginal effects of each genetic marker on disease. In this paper, the authors propose an efficient and easily implemented 2-step analysis of genome-wide association study data aimed at identifying genes involved in a gene-environment interaction. The procedure complements screening for marginal genetic effects and thus has the potential to uncover new genetic signals that have not been identified previously.. breast-cancer| air-pollution| susceptibility| risk| asthma| loci| replication| children| smoking.	JAN 15-2009	breast-cancer| air-pollution| susceptibility| risk| asthma| loci| replication| children| smoking	Murcray, CE; Lewinger, JP; Gauderman, WJ	Gene-Environment Interaction in Genome-Wide Association Studies		AMERICAN JOURNAL OF EPIDEMIOLOGY		BREAST-CANCER; AIR-POLLUTION; SUSCEPTIBILITY; RISK; ASTHMA; LOCI; REPLICATION; CHILDREN; SMOKING	It is a commonly held belief that most complex diseases (e.g., diabetes, asthma, cancer) are affected in part by interactions between genes and environmental factors. However, investigators conducting genome-wide association studies typically test for only the marginal effects of each genetic marker on disease. In this paper, the authors propose an efficient and easily implemented 2-step analysis of genome-wide association study data aimed at identifying genes involved in a gene-environment interaction. The procedure complements screening for marginal genetic effects and thus has the potential to uncover new genetic signals that have not been identified previously.	24	147	2009	8	10.1093/aje/kwn353	Public, Environmental & Occupational Health
Environmental risk factors and allergic bronchial asthma. The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic potential. In addition, by inducing airway inflammation, which increases airway permeability, pollutants overcome the mucosal barrier and could be able to 'prime' allergen-induced responses. There are also observations that a thunderstorm occurring during pollen season can induce severe asthma attacks in pollinosis patients. After rupture by thunderstorm, pollen grains may release part of their cytoplasmic content, including inhalable, allergen-carrying paucimicronic particles.. air pollution| bronchial asthma| pollen allergy| respiratory allergy| thunderstorm-associated asthma| urban air pollution|outdoor air-pollution| thunderstorm-associated asthma| respiratory health survey| diesel exhaust particles| fine-particulate matter| grass-pollen allergen| ppm nitrogen-dioxide| ozone exposure| pulmonary-function| sulfur-dioxide.	SEP-2005	air pollution| bronchial asthma| pollen allergy| respiratory allergy| thunderstorm-associated asthma| urban air pollution|outdoor air-pollution| thunderstorm-associated asthma| respiratory health survey| diesel exhaust particles| fine-particulate matter| grass-pollen allergen| ppm nitrogen-dioxide| ozone exposure| pulmonary-function| sulfur-dioxide	D'Amato, G; Liccardi, G; D'Amato, M; Holgate, S	Environmental risk factors and allergic bronchial asthma		CLINICAL AND EXPERIMENTAL ALLERGY	air pollution; bronchial asthma; pollen allergy; respiratory allergy; thunderstorm-associated asthma; urban air pollution	OUTDOOR AIR-POLLUTION; THUNDERSTORM-ASSOCIATED ASTHMA; RESPIRATORY HEALTH SURVEY; DIESEL EXHAUST PARTICLES; FINE-PARTICULATE MATTER; GRASS-POLLEN ALLERGEN; PPM NITROGEN-DIOXIDE; OZONE EXPOSURE; PULMONARY-FUNCTION; SULFUR-DIOXIDE	The prevalence of allergic respiratory diseases such as bronchial asthma has increased in recent years, especially in industrialized countries. A change in the genetic predisposition is an unlikely cause of the increase in allergic diseases because genetic changes in a population require several generations. Consequently, this increase may be explained by changes in environmental factors, including indoor and outdoor air pollution. Over the past two decades, there has been increasing interest in studies of air pollution and its effects on human health. Although the role played by outdoor pollutants in allergic sensitization of the airways has yet to be clarified, a body of evidence suggests that urbanization, with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases observed in most industrialized countries, and there is considerable evidence that asthmatic persons are at increased risk of developing asthma exacerbations with exposure to ozone, nitrogen dioxide, sulphur dioxide and inhalable particulate matter. However, it is not easy to evaluate the impact of air pollution on the timing of asthma exacerbations and on the prevalence of asthma in general. As concentrations of airborne allergens and air pollutants are frequently increased contemporaneously, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of allergic respiratory allergy and bronchial asthma. Pollinosis is frequently used to study the interrelationship between air pollution and respiratory allergy. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc) can affect both components (biological and chemical) of this interaction. By attaching to the surface of pollen grains and of plant-derived particles of paucimicronic size, pollutants could modify not only the morphology of these antigen-carrying agents but also their allergenic potential. In addition, by inducing airway inflammation, which increases airway permeability, pollutants overcome the mucosal barrier and could be able to 'prime' allergen-induced responses. There are also observations that a thunderstorm occurring during pollen season can induce severe asthma attacks in pollinosis patients. After rupture by thunderstorm, pollen grains may release part of their cytoplasmic content, including inhalable, allergen-carrying paucimicronic particles.	162	147	2005	12	10.1111/j.1365-2222.2005.02328.x	Allergy; Immunology
Microbial exposure of rural school children, as assessed by levels of N-acetyl-muramic acid in mattress dust, and its association with respiratory health. Background: Endotoxin exposure has been shown to be associated with a decreased prevalence of atopic sensitization and symptoms. Yet endotoxin represents only a part of the indoor microbial exposure. Muramic acid, a constituent of peptidoglycan, is present in gram-negative and gram-positive bacteria in the environment and may therefore serve as an additional marker of microbial exposure. Objective: To study the factors determining the level of indoor exposure to muramic acid/peptidoglycan, as well as its potential association with respiratory health. Methods: In 553 farm and nonfarm school children from Austria, Switzerland, and Germany, mattress dust muramic acid concentrations were determined, and health was assessed by using IgE measurements and questionnaire information. Results: The muramic acid concentration was found to be significantly higher in dust from farm children's mattresses than in dust from nonfarm children's mattresses (157 vs 131 ng/mg). Children with higher mattress dust muramic acid concentrations had a significantly lower prevalence of wheezing (odds ratio of highest vs lowest tertile of muramic acid concentration, 0.3; 95 % CI, 0.1-0.9), regardless of farming status and endotoxin exposure. The association for asthma was similar, and no association was found with atopic sensitization. Conclusion: Next to endotoxin, muramic acid provides us with an independent marker of microbial exposure. Unlike endotoxin, muramic acid was inversely associated with wheezing rather than with atopic sensitization.. farming| allergy| asthma| peptidoglycan| muramic acid| microbial exposure| hygiene hypothesis|tandem mass-spectrometry| allergic sensitization| endotoxin levels| hay-fever| farmers children| asthma| environments| age| determinants| community.	MAY-2004	farming| allergy| asthma| peptidoglycan| muramic acid| microbial exposure| hygiene hypothesis|tandem mass-spectrometry| allergic sensitization| endotoxin levels| hay-fever| farmers children| asthma| environments| age| determinants| community	van Strien, RT; Engel, R; Holst, O; Bufe, A; Eder, W; Waser, M; Braun-Fahrlander, C; Riedler, J; Nowak, D; von Mutius, E	Microbial exposure of rural school children, as assessed by levels of N-acetyl-muramic acid in mattress dust, and its association with respiratory health		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	farming; allergy; asthma; peptidoglycan; muramic acid; microbial exposure; hygiene hypothesis	TANDEM MASS-SPECTROMETRY; ALLERGIC SENSITIZATION; ENDOTOXIN LEVELS; HAY-FEVER; FARMERS CHILDREN; ASTHMA; ENVIRONMENTS; AGE; DETERMINANTS; COMMUNITY	Background: Endotoxin exposure has been shown to be associated with a decreased prevalence of atopic sensitization and symptoms. Yet endotoxin represents only a part of the indoor microbial exposure. Muramic acid, a constituent of peptidoglycan, is present in gram-negative and gram-positive bacteria in the environment and may therefore serve as an additional marker of microbial exposure. Objective: To study the factors determining the level of indoor exposure to muramic acid/peptidoglycan, as well as its potential association with respiratory health. Methods: In 553 farm and nonfarm school children from Austria, Switzerland, and Germany, mattress dust muramic acid concentrations were determined, and health was assessed by using IgE measurements and questionnaire information. Results: The muramic acid concentration was found to be significantly higher in dust from farm children's mattresses than in dust from nonfarm children's mattresses (157 vs 131 ng/mg). Children with higher mattress dust muramic acid concentrations had a significantly lower prevalence of wheezing (odds ratio of highest vs lowest tertile of muramic acid concentration, 0.3; 95 % CI, 0.1-0.9), regardless of farming status and endotoxin exposure. The association for asthma was similar, and no association was found with atopic sensitization. Conclusion: Next to endotoxin, muramic acid provides us with an independent marker of microbial exposure. Unlike endotoxin, muramic acid was inversely associated with wheezing rather than with atopic sensitization.	30	147	2004	8	10.1016/j.jaci.2004.01.078	Allergy; Immunology
Lung hyperpermeability and asthma prevalence in schoolchildren: unexpected associations with the attendance at indoor chlorinated swimming pools. Aims: To study whether exposure to nitrogen trichloride in indoor chlorinated pools may affect the respiratory epithelium of children and increase the risk of some lung diseases such as asthma. Methods: In 226 healthy children, serum surfactant associated proteins A and B (SP-A and SP-B), 16 kDa Clara cell protein (CC 16), and IgE were measured. Lung specific proteins were measured in the serum of 16 children and 13 adults before and after exposure to NCl3, in an indoor chlorinated pool. Relations between pool attendance and asthma prevalence were studied in 1881 children. Asthma was screened with the exercise induced bronchoconstriction test (EIB). Results: Pool attendance was the most consistent predictor of lung epithelium permeability. A positive dose-effect relation was found with cumulated pool attendance and serum SP-A and SP-B. Serum IgE. was unrelated to pool attendance, but correlated positively with lung hyperpermeability as assessed by serum SP-B. Changes in serum levels of lung proteins were reproduced in children and adults attending an indoor pool. Serum SP-A and SP-B were already significantly increased after one hour on the pool side without swimming. Positive EIB and total asthma prevalence were significantly correlated with cumulated pool attendance indices. Conclusions: Regular attendance at chlorinated pools by Young children is associated with an exposure dependent increase in lung epithelium permeability and increase in the risk of developing asthma especially in association with other risk factors. We therefore postulate that the increasing exposure of children to chlorination products in indoor pools might be an important cause of the rising incidence of childhood asthma and allergic diseases in industrialised countries. Further epidemiological studies should be undertaken to test this hypothesis.. clara cell protein| respiratory symptoms| bronchial responsiveness| nitrogen trichloride| serum| children| cc16| disinfectant| swimmers| smokers.	JUN-2003	clara cell protein| respiratory symptoms| bronchial responsiveness| nitrogen trichloride| serum| children| cc16| disinfectant| swimmers| smokers	Bernard, A; Carbonnelle, S; Michel, O; Higuet, S; de Burbure, C; Buchet, JP; Hermans, C; Dumont, X; Doyle, I	Lung hyperpermeability and asthma prevalence in schoolchildren: unexpected associations with the attendance at indoor chlorinated swimming pools		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		CLARA CELL PROTEIN; RESPIRATORY SYMPTOMS; BRONCHIAL RESPONSIVENESS; NITROGEN TRICHLORIDE; SERUM; CHILDREN; CC16; DISINFECTANT; SWIMMERS; SMOKERS	Aims: To study whether exposure to nitrogen trichloride in indoor chlorinated pools may affect the respiratory epithelium of children and increase the risk of some lung diseases such as asthma. Methods: In 226 healthy children, serum surfactant associated proteins A and B (SP-A and SP-B), 16 kDa Clara cell protein (CC 16), and IgE were measured. Lung specific proteins were measured in the serum of 16 children and 13 adults before and after exposure to NCl3, in an indoor chlorinated pool. Relations between pool attendance and asthma prevalence were studied in 1881 children. Asthma was screened with the exercise induced bronchoconstriction test (EIB). Results: Pool attendance was the most consistent predictor of lung epithelium permeability. A positive dose-effect relation was found with cumulated pool attendance and serum SP-A and SP-B. Serum IgE. was unrelated to pool attendance, but correlated positively with lung hyperpermeability as assessed by serum SP-B. Changes in serum levels of lung proteins were reproduced in children and adults attending an indoor pool. Serum SP-A and SP-B were already significantly increased after one hour on the pool side without swimming. Positive EIB and total asthma prevalence were significantly correlated with cumulated pool attendance indices. Conclusions: Regular attendance at chlorinated pools by Young children is associated with an exposure dependent increase in lung epithelium permeability and increase in the risk of developing asthma especially in association with other risk factors. We therefore postulate that the increasing exposure of children to chlorination products in indoor pools might be an important cause of the rising incidence of childhood asthma and allergic diseases in industrialised countries. Further epidemiological studies should be undertaken to test this hypothesis.	45	147	2003	10	10.1136/oem.60.6.385	Public, Environmental & Occupational Health
Dysfunction and remodeling of the mouse airway persist after resolution of acute allergen-induced airway inflammation. The mechanisms underlying airway hyperresponsiveness remain unclear, although airway inflammation and remodeling are likely important contributing factors. We hypothesized that airway physiology would differ between mice subjected to brief or chronic allergen exposure, and that these differences would be associated with characteristic inflammatory markers and indices of airway remodeling. BALB/c mice were sensitized to ovalbumin and studied at several time points following brief or chronic allergen challenge protocols. By measuring airway responses to methacholine, we demonstrated increases in maximal inducible bronchoconstriction that persisted for 8 wk following either brief or chronic allergen challenge; we also observed increases in airway reactivity, although it was only in chronically challenged mice that these changes persisted beyond the resolution of allergen-induced inflammation. Using airway morphometry, we further demonstrated that increases in maximal bronchoconstriction were associated with increases in airway contractile tissue in both models, and that chronic, but not brief, allergen challenge resulted in subepithelial fibrosis. Our observations that different aspects of sustained airway dysfunction and remodeling persist beyond the resolution of acute inflammatory events support the concept that remodeling occurs as a consequence of allergic airway inflammation, and that these structural changes contribute independently to the persistence of airway hyperresponsiveness.. obstructive pulmonary-disease| mild asthma| subepithelial fibrosis| induced increase| murine model| hyperresponsiveness| responsiveness| hyperreactivity| methacholine| eosinophilia.	NOV-2002	obstructive pulmonary-disease| mild asthma| subepithelial fibrosis| induced increase| murine model| hyperresponsiveness| responsiveness| hyperreactivity| methacholine| eosinophilia	Leigh, R; Ellis, R; Wattie, J; Southam, DS; de Hoogh, M; Gauldie, J; O'Byrne, PM; Inman, MD	Dysfunction and remodeling of the mouse airway persist after resolution of acute allergen-induced airway inflammation		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		OBSTRUCTIVE PULMONARY-DISEASE; MILD ASTHMA; SUBEPITHELIAL FIBROSIS; INDUCED INCREASE; MURINE MODEL; HYPERRESPONSIVENESS; RESPONSIVENESS; HYPERREACTIVITY; METHACHOLINE; EOSINOPHILIA	The mechanisms underlying airway hyperresponsiveness remain unclear, although airway inflammation and remodeling are likely important contributing factors. We hypothesized that airway physiology would differ between mice subjected to brief or chronic allergen exposure, and that these differences would be associated with characteristic inflammatory markers and indices of airway remodeling. BALB/c mice were sensitized to ovalbumin and studied at several time points following brief or chronic allergen challenge protocols. By measuring airway responses to methacholine, we demonstrated increases in maximal inducible bronchoconstriction that persisted for 8 wk following either brief or chronic allergen challenge; we also observed increases in airway reactivity, although it was only in chronically challenged mice that these changes persisted beyond the resolution of allergen-induced inflammation. Using airway morphometry, we further demonstrated that increases in maximal bronchoconstriction were associated with increases in airway contractile tissue in both models, and that chronic, but not brief, allergen challenge resulted in subepithelial fibrosis. Our observations that different aspects of sustained airway dysfunction and remodeling persist beyond the resolution of acute inflammatory events support the concept that remodeling occurs as a consequence of allergic airway inflammation, and that these structural changes contribute independently to the persistence of airway hyperresponsiveness.	45	147	2002	10	10.1165/rcmb.2002-0048OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Breastfeeding duration is a risk factor for atopic eczema. Background The results of numerous studies on the influence of breastfeeding in the prevention of atopic disorders are often contradictory. One of the most important problems is confounding by other lifestyle factors. Objective The aim of the present study was to analyse the effect of any breastfeeding duration on the prevalence of atopic eczema in the first seven years of life taking into account other risk factors. Methods In an observational birth cohort study 1314 infants born in 1990 were followed-up for seven years. At 3, 6, 12, 18, 24 months and every year thereafter, parents were interviewed and filled in questionnaires, children were examined and blood was taken for in vitro allergy tests. Generalized Estimation Equations (GEE)-models were used to model risk factors for the prevalence of atopic eczema and for confounder adjustment Results Breastfeeding was carried out for longer if at least one parent had eczema, the mother was older, did not smoke in pregnancy, and the family had a high social status. The prevalence of atopic eczema in the first seven years increased with each year of age (OR 1.05; 95% CI 1.01-1.09 for each year), with each additional month of breastfeeding (1.03; 1.00-1.06 for each additional month), with a history of parental atopic eczema (2.06; 1.38-3.08), and if other atopic signs and symptoms appeared, especially specific sensitization (1.53; 1.25-1.88), and asthma (1.41; 1.07-1.85). Although breastfeeding should be recommended for all infants, it does not prevent eczema in children with a genetic risk. Conclusion Parental eczema is the major risk factor for eczema. But in this study, each month of breastfeeding also increased the risk.. atopic eczema| children| breastfeeding|cows milk allergy| breast-fed infants| disease| childhood| proteins| exposure| ige| age.	FEB-2002	atopic eczema| children| breastfeeding|cows milk allergy| breast-fed infants| disease| childhood| proteins| exposure| ige| age	Bergmann, RL; Diepgen, TL; Kuss, O; Bergmann, KE; Kujat, J; Dudenhausen, JW; Wahn, U	Breastfeeding duration is a risk factor for atopic eczema		CLINICAL AND EXPERIMENTAL ALLERGY	atopic eczema; children; breastfeeding	COWS MILK ALLERGY; BREAST-FED INFANTS; DISEASE; CHILDHOOD; PROTEINS; EXPOSURE; IGE; AGE	Background The results of numerous studies on the influence of breastfeeding in the prevention of atopic disorders are often contradictory. One of the most important problems is confounding by other lifestyle factors. Objective The aim of the present study was to analyse the effect of any breastfeeding duration on the prevalence of atopic eczema in the first seven years of life taking into account other risk factors. Methods In an observational birth cohort study 1314 infants born in 1990 were followed-up for seven years. At 3, 6, 12, 18, 24 months and every year thereafter, parents were interviewed and filled in questionnaires, children were examined and blood was taken for in vitro allergy tests. Generalized Estimation Equations (GEE)-models were used to model risk factors for the prevalence of atopic eczema and for confounder adjustment Results Breastfeeding was carried out for longer if at least one parent had eczema, the mother was older, did not smoke in pregnancy, and the family had a high social status. The prevalence of atopic eczema in the first seven years increased with each year of age (OR 1.05; 95% CI 1.01-1.09 for each year), with each additional month of breastfeeding (1.03; 1.00-1.06 for each additional month), with a history of parental atopic eczema (2.06; 1.38-3.08), and if other atopic signs and symptoms appeared, especially specific sensitization (1.53; 1.25-1.88), and asthma (1.41; 1.07-1.85). Although breastfeeding should be recommended for all infants, it does not prevent eczema in children with a genetic risk. Conclusion Parental eczema is the major risk factor for eczema. But in this study, each month of breastfeeding also increased the risk.	32	147	2002	5	10.1046/j.1365-2222.2002.01274.x	Allergy; Immunology
Mouse allergen. II. The relationship of mouse allergen exposure to mouse sensitization and asthma morbidity in inner-city children with asthma. Background: Although mouse allergen is known to cause occupational asthma in laboratory workers, its potential significance in home environments has never been studied. Objective: This study was designed to define the prevalence of mouse sensitivity and its relationship to mouse allergen exposure and disease activity in inner-city children with asthma, Methods: A subset Of 499 subjects from the National Cooperative Inner-City Asthma Study had dust samples adequate for mouse allergen analysis, as well as valid puncture skin test (PST) results, Data were analyzed to relate mouse allergen exposure and other risk factors to mouse sensitization and asthma morbidity, Results: Eighty-nine (18%) of the 499 children had a positive mouse skin test response, Children whose homes had mouse allergen levels above the median (1.60 mug/g) in the kitchen had a significantly higher rate of mouse sensitization (23% vs 11%, P = .007). Atopy was also significantly related to mouse sensitization, with 40% of those with more than 4 positive PST responses having mouse sensitivity compared with 4% of those with no other positive PST responses (P < .0001). When atopy and exposure were considered together, 53% of those with more than 4 positive PST responses and allergen levels above the median had a positive PST response to mouse allergen compared with 22% of those with more than 4 positive PST responses and allergen levels below the median (P < .0001). The relationship among mouse allergen exposure, sensitization, and any measures of asthma morbidity was not statistically significant, Conclusions: Mouse allergen may be an important indoor allergen in inner-city children with asthma, with exposure and atopy contributing to mouse sensitization.. mouse allergen| indoor allergens| inner-city asthma| sensitization| asthma morbidity|der-p-i| mite| risk| childhood| cat.	DEC-2000	mouse allergen| indoor allergens| inner-city asthma| sensitization| asthma morbidity|der-p-i| mite| risk| childhood| cat	Phipatanakul, W; Eggleston, PA; Wright, EC; Wood, RA	Mouse allergen. II. The relationship of mouse allergen exposure to mouse sensitization and asthma morbidity in inner-city children with asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	mouse allergen; indoor allergens; inner-city asthma; sensitization; asthma morbidity	DER-P-I; MITE; RISK; CHILDHOOD; CAT	Background: Although mouse allergen is known to cause occupational asthma in laboratory workers, its potential significance in home environments has never been studied. Objective: This study was designed to define the prevalence of mouse sensitivity and its relationship to mouse allergen exposure and disease activity in inner-city children with asthma, Methods: A subset Of 499 subjects from the National Cooperative Inner-City Asthma Study had dust samples adequate for mouse allergen analysis, as well as valid puncture skin test (PST) results, Data were analyzed to relate mouse allergen exposure and other risk factors to mouse sensitization and asthma morbidity, Results: Eighty-nine (18%) of the 499 children had a positive mouse skin test response, Children whose homes had mouse allergen levels above the median (1.60 mug/g) in the kitchen had a significantly higher rate of mouse sensitization (23% vs 11%, P = .007). Atopy was also significantly related to mouse sensitization, with 40% of those with more than 4 positive PST responses having mouse sensitivity compared with 4% of those with no other positive PST responses (P < .0001). When atopy and exposure were considered together, 53% of those with more than 4 positive PST responses and allergen levels above the median had a positive PST response to mouse allergen compared with 22% of those with more than 4 positive PST responses and allergen levels below the median (P < .0001). The relationship among mouse allergen exposure, sensitization, and any measures of asthma morbidity was not statistically significant, Conclusions: Mouse allergen may be an important indoor allergen in inner-city children with asthma, with exposure and atopy contributing to mouse sensitization.	23	147	2000	6		Allergy; Immunology
Association Between Participation in a Multipayer Medical Home Intervention and Changes in Quality, Utilization, and Costs of Care. IMPORTANCE Interventions to transform primary care practices into medical homes are increasingly common, but their effectiveness in improving quality and containing costs is unclear. OBJECTIVE To measure associations between participation in the Southeastern Pennsylvania Chronic Care Initiative, one of the earliest and largest multipayer medical home pilots conducted in the United States, and changes in the quality, utilization, and costs of care. DESIGN, SETTING, AND PARTICIPANTS Thirty-two volunteering primary care practices participated in the pilot (conducted from June 1, 2008, to May 31, 2011). We surveyed pilot practices to compare their structural capabilities at the pilot's beginning and end. Using claims data from 4 participating health plans, we compared changes (in each year, relative to before the intervention) in the quality, utilization, and costs of care delivered to 64 243 patients who were attributed to pilot practices and 55 959 patients attributed to 29 comparison practices (selected for size, specialty, and location similar to pilot practices) using a difference-in-differences design. EXPOSURES Pilot practices received disease registries and technical assistance and could earn bonus payments for achieving patient-centered medical home recognition by the National Committee for Quality Assurance (NCQA). MAIN OUTCOMES AND MEASURES Practice structural capabilities; performance on 11 quality measures for diabetes, asthma, and preventive care; utilization of hospital, emergency department, and ambulatory care; standardized costs of care. RESULTS Pilot practices successfully achieved NCQA recognition and adopted new structural capabilities such as registries to identify patients overdue for chronic disease services. Pilot participation was associated with statistically significantly greater performance improvement, relative to comparison practices, on 1 of 11 investigated quality measures: nephropathy screening in diabetes (adjusted performance of 82.7% vs 71.7% by year 3, P<.001). Pilot participation was not associated with statistically significant changes in utilization or costs of care. Pilot practices accumulated average bonuses of $92 000 per primary care physician during the 3-year intervention. CONCLUSIONS AND RELEVANCE A multipayer medical home pilot, in which participating practices adopted new structural capabilities and received NCQA certification, was associated with limited improvements in quality and was not associated with reductions in utilization of hospital, emergency department, or ambulatory care services or total costs over 3 years. These findings suggest that medical home interventions may need further refinement.. longitudinal data-analysis| structural capabilities| transformation| efficiency| models| trial| will.	FEB 26-2014	longitudinal data-analysis| structural capabilities| transformation| efficiency| models| trial| will	Friedberg, MW; Schneider, EC; Rosenthal, MB; Volpp, KG; Werner, RM	Association Between Participation in a Multipayer Medical Home Intervention and Changes in Quality, Utilization, and Costs of Care		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		LONGITUDINAL DATA-ANALYSIS; STRUCTURAL CAPABILITIES; TRANSFORMATION; EFFICIENCY; MODELS; TRIAL; WILL	IMPORTANCE Interventions to transform primary care practices into medical homes are increasingly common, but their effectiveness in improving quality and containing costs is unclear. OBJECTIVE To measure associations between participation in the Southeastern Pennsylvania Chronic Care Initiative, one of the earliest and largest multipayer medical home pilots conducted in the United States, and changes in the quality, utilization, and costs of care. DESIGN, SETTING, AND PARTICIPANTS Thirty-two volunteering primary care practices participated in the pilot (conducted from June 1, 2008, to May 31, 2011). We surveyed pilot practices to compare their structural capabilities at the pilot's beginning and end. Using claims data from 4 participating health plans, we compared changes (in each year, relative to before the intervention) in the quality, utilization, and costs of care delivered to 64 243 patients who were attributed to pilot practices and 55 959 patients attributed to 29 comparison practices (selected for size, specialty, and location similar to pilot practices) using a difference-in-differences design. EXPOSURES Pilot practices received disease registries and technical assistance and could earn bonus payments for achieving patient-centered medical home recognition by the National Committee for Quality Assurance (NCQA). MAIN OUTCOMES AND MEASURES Practice structural capabilities; performance on 11 quality measures for diabetes, asthma, and preventive care; utilization of hospital, emergency department, and ambulatory care; standardized costs of care. RESULTS Pilot practices successfully achieved NCQA recognition and adopted new structural capabilities such as registries to identify patients overdue for chronic disease services. Pilot participation was associated with statistically significantly greater performance improvement, relative to comparison practices, on 1 of 11 investigated quality measures: nephropathy screening in diabetes (adjusted performance of 82.7% vs 71.7% by year 3, P<.001). Pilot participation was not associated with statistically significant changes in utilization or costs of care. Pilot practices accumulated average bonuses of $92 000 per primary care physician during the 3-year intervention. CONCLUSIONS AND RELEVANCE A multipayer medical home pilot, in which participating practices adopted new structural capabilities and received NCQA certification, was associated with limited improvements in quality and was not associated with reductions in utilization of hospital, emergency department, or ambulatory care services or total costs over 3 years. These findings suggest that medical home interventions may need further refinement.	42	146	2014	11	10.1001/jama.2014.353	General & Internal Medicine
"New Paradigms in Type 2 Immunity. Nearly half of the world's population harbors helminth infections or suffers from allergic disorders. A common feature of this population is the so-called ""type 2 immune response,"" which confers protection against helminths, but also promotes pathologic responses associated with allergic inflammation. However, the mechanisms that initiate and control type 2 responses remain enigmatic. Recent advances have revealed a role for the innate immune system in orchestrating type 2 responses against a bewildering array of stimuli, from nanometer-sized allergens to 20-meter-long helminth parasites. Here, we review these advances and suggest that the human immune system has evolved multiple mechanisms of sensing such stimuli, from recognition of molecular patterns via innate immune receptors to detecting metabolic changes and tissue damage caused by these stimuli.. t-helper-cell| thymic stromal lymphopoietin| antigen-presenting cells| dust mite allergen| responses in-vivo| dendritic cells| epithelial-cells| innate immunity| il-4 production| lymphoid-cells."	JUL 27-2012	t-helper-cell| thymic stromal lymphopoietin| antigen-presenting cells| dust mite allergen| responses in-vivo| dendritic cells| epithelial-cells| innate immunity| il-4 production| lymphoid-cells	Pulendran, B; Artis, D	New Paradigms in Type 2 Immunity		SCIENCE		T-HELPER-CELL; THYMIC STROMAL LYMPHOPOIETIN; ANTIGEN-PRESENTING CELLS; DUST MITE ALLERGEN; RESPONSES IN-VIVO; DENDRITIC CELLS; EPITHELIAL-CELLS; INNATE IMMUNITY; IL-4 PRODUCTION; LYMPHOID-CELLS	"Nearly half of the world's population harbors helminth infections or suffers from allergic disorders. A common feature of this population is the so-called ""type 2 immune response,"" which confers protection against helminths, but also promotes pathologic responses associated with allergic inflammation. However, the mechanisms that initiate and control type 2 responses remain enigmatic. Recent advances have revealed a role for the innate immune system in orchestrating type 2 responses against a bewildering array of stimuli, from nanometer-sized allergens to 20-meter-long helminth parasites. Here, we review these advances and suggest that the human immune system has evolved multiple mechanisms of sensing such stimuli, from recognition of molecular patterns via innate immune receptors to detecting metabolic changes and tissue damage caused by these stimuli."	72	146	2012	5	10.1126/science.1221064	Science & Technology - Other Topics
Traffic-related air pollution and childhood respiratory symptoms, function and allergies. Background: Urban air pollution can trigger asthma symptoms in children, but there is conflicting evidence on effects of long-term exposure on lung function, onset of airway disease and allergic sensitization. Methods: The spatial distribution of nitrogen oxides from traffic (traffic-NOx) and inhalable particulate matter from traffic (traffic-PM10) in the study area was assessed with emission databases and dispersion modeling. Estimated levels were used to assign first-year exposure levels for children in a prospective birth cohort (n = 4089), by linking to geocoded home addresses. Parents in 4 Swedish municipalities provided questionnaire data on symptoms and exposures when the children were 2 months and 1, 2, and 4-year-old. At 4 years, 73% of the children underwent clinical examination including peak expiratory flow and specific IgE measurements. Results: Exposure to air pollution from traffic during the first year of life was associated with an excess risk of persistent wheezing (odds ratio [OR] for 44 mu g/m(3) [5th-95th percentile] difference in traffic-NO, = 1.60; 95% confidence interval [Cl] = 1.09-2.36). Similar results were found for sensitization (measured as specific IgE) to inhalant allergens, especially pollen (OR for traffic-NO, = 1.67; 95% CI = 1.10-2.53), at the age of 4 years. Traffic-related air pollution exposure during the first year of life was also associated with lower lung function at 4 years of age. Results were similar using traffic-NOx and traffic-PM10 as indicators. Conclusions: Exposure to moderate levels of locally emitted air pollution from traffic early in life appears to influence the development of airway disease and sensitization in preschool children.. long-term exposure| lung-function growth| 3 european areas| nitrogen-dioxide| pulmonary-function| birth cohort| children| health| asthma| schoolchildren.	MAY-2008	long-term exposure| lung-function growth| 3 european areas| nitrogen-dioxide| pulmonary-function| birth cohort| children| health| asthma| schoolchildren	Nordling, E; Berglind, N; Melen, E; Emenius, G; Hallberg, J; Nyberg, F; Pershagen, G; Svartengren, M; Wickman, M; Bellander, T	Traffic-related air pollution and childhood respiratory symptoms, function and allergies		EPIDEMIOLOGY		LONG-TERM EXPOSURE; LUNG-FUNCTION GROWTH; 3 EUROPEAN AREAS; NITROGEN-DIOXIDE; PULMONARY-FUNCTION; BIRTH COHORT; CHILDREN; HEALTH; ASTHMA; SCHOOLCHILDREN	Background: Urban air pollution can trigger asthma symptoms in children, but there is conflicting evidence on effects of long-term exposure on lung function, onset of airway disease and allergic sensitization. Methods: The spatial distribution of nitrogen oxides from traffic (traffic-NOx) and inhalable particulate matter from traffic (traffic-PM10) in the study area was assessed with emission databases and dispersion modeling. Estimated levels were used to assign first-year exposure levels for children in a prospective birth cohort (n = 4089), by linking to geocoded home addresses. Parents in 4 Swedish municipalities provided questionnaire data on symptoms and exposures when the children were 2 months and 1, 2, and 4-year-old. At 4 years, 73% of the children underwent clinical examination including peak expiratory flow and specific IgE measurements. Results: Exposure to air pollution from traffic during the first year of life was associated with an excess risk of persistent wheezing (odds ratio [OR] for 44 mu g/m(3) [5th-95th percentile] difference in traffic-NO, = 1.60; 95% confidence interval [Cl] = 1.09-2.36). Similar results were found for sensitization (measured as specific IgE) to inhalant allergens, especially pollen (OR for traffic-NO, = 1.67; 95% CI = 1.10-2.53), at the age of 4 years. Traffic-related air pollution exposure during the first year of life was also associated with lower lung function at 4 years of age. Results were similar using traffic-NOx and traffic-PM10 as indicators. Conclusions: Exposure to moderate levels of locally emitted air pollution from traffic early in life appears to influence the development of airway disease and sensitization in preschool children.	42	146	2008	8	10.1097/EDE.0b013e31816alce3	Public, Environmental & Occupational Health
How epidemiology has challenged 3 prevailing concepts about atopic dermatitis. We challenge 3 prevailing concepts in understanding atopic dermatitis using data from epidemiologic studies. First, we show that although atopy is associated with atopic dermatitis to some degree, its importance is not likely to be a simple cause-and-effect relationship, especially at a population level. Our epidemiologic data do not exclude a contributory role for IgE-mediated immunologic processes, especially in those with existing and severe disease. Second, evidence is presented that does not support a straightforward inverse relationship between infections and atopic dermatitis risk. A link, if present, is likely to be more complex, depending critically on the timing and type of infectious exposure. Third, recent evidence suggests that the risk of subsequent childhood asthma is not increased in children with early atopic dermatitis who are not also early wheezers, suggesting a comanifestation of phenotypes rather than a progressive atopic march. Collectively, these observations underline the importance of epidemiologic studies conducted at a population level to gain a more balanced understanding of the enigma of atopic dermatitis.. atopy| atopic march| eczema| hygiene|eczema| sensitization| children| allergy| asthma| association| prevalence| diseases| schoolchildren| rhinitis.	JUL-2006	atopy| atopic march| eczema| hygiene|eczema| sensitization| children| allergy| asthma| association| prevalence| diseases| schoolchildren| rhinitis	Williams, H; Flohr, C	How epidemiology has challenged 3 prevailing concepts about atopic dermatitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopy; atopic march; eczema; hygiene	ECZEMA; SENSITIZATION; CHILDREN; ALLERGY; ASTHMA; ASSOCIATION; PREVALENCE; DISEASES; SCHOOLCHILDREN; RHINITIS	We challenge 3 prevailing concepts in understanding atopic dermatitis using data from epidemiologic studies. First, we show that although atopy is associated with atopic dermatitis to some degree, its importance is not likely to be a simple cause-and-effect relationship, especially at a population level. Our epidemiologic data do not exclude a contributory role for IgE-mediated immunologic processes, especially in those with existing and severe disease. Second, evidence is presented that does not support a straightforward inverse relationship between infections and atopic dermatitis risk. A link, if present, is likely to be more complex, depending critically on the timing and type of infectious exposure. Third, recent evidence suggests that the risk of subsequent childhood asthma is not increased in children with early atopic dermatitis who are not also early wheezers, suggesting a comanifestation of phenotypes rather than a progressive atopic march. Collectively, these observations underline the importance of epidemiologic studies conducted at a population level to gain a more balanced understanding of the enigma of atopic dermatitis.	38	146	2006	5	10.1016/j.jaci.2006.04.043	Allergy; Immunology
Chemokines: Roles in leukocyte development, trafficking, and effector function. Chemokines, representing a large superfamily of 8- to 15-kd proteins, were originally discovered through their ability to recruit various cell types into sites of inflammation. It is now clear that these molecules play a much wider role in immune homeostasis, playing key roles in driving the maturation, homing, and activation of leukocytes. In this review we analyze the roles chemokines play in the development, recruitment, and activation of leukocytes. Because signaling from the receptors drives these processes, signal transduction from chemokine receptors will also be reviewed. Taken together, we highlight the various points at which chemokines contribute to allergic inflammation and at which their targeting might contribute to new therapies for type I hypersensitivity reactions.. chemokines| receptors| allergy| asthma| signal transduction|human mast-cells| macrophage inflammatory protein-1-alpha| eotaxin receptor ccr3| cd4(+) t-cells| fc-epsilon-ri| late-phase| dendritic cells| in-vivo| allergic conjunctivitis| neutrophil migration.	JUN-2003	chemokines| receptors| allergy| asthma| signal transduction|human mast-cells| macrophage inflammatory protein-1-alpha| eotaxin receptor ccr3| cd4(+) t-cells| fc-epsilon-ri| late-phase| dendritic cells| in-vivo| allergic conjunctivitis| neutrophil migration	Ono, SJ; Nakamura, T; Miyazaki, D; Ohbayashi, M; Dawson, M; Toda, M	Chemokines: Roles in leukocyte development, trafficking, and effector function		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	chemokines; receptors; allergy; asthma; signal transduction	HUMAN MAST-CELLS; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; EOTAXIN RECEPTOR CCR3; CD4(+) T-CELLS; FC-EPSILON-RI; LATE-PHASE; DENDRITIC CELLS; IN-VIVO; ALLERGIC CONJUNCTIVITIS; NEUTROPHIL MIGRATION	Chemokines, representing a large superfamily of 8- to 15-kd proteins, were originally discovered through their ability to recruit various cell types into sites of inflammation. It is now clear that these molecules play a much wider role in immune homeostasis, playing key roles in driving the maturation, homing, and activation of leukocytes. In this review we analyze the roles chemokines play in the development, recruitment, and activation of leukocytes. Because signaling from the receptors drives these processes, signal transduction from chemokine receptors will also be reviewed. Taken together, we highlight the various points at which chemokines contribute to allergic inflammation and at which their targeting might contribute to new therapies for type I hypersensitivity reactions.	129	146	2003	15	10.1067/mai.2003.1594	Allergy; Immunology
Endotoxin-stimulated innate immunity: A contributing factor for asthma. Exposure to airborne endotoxin in infancy may protect against asthma by promoting enhanced T(H)1 response and tolerance to allergens. On the other hand, later in life, it adversely affects patients with asthma. Endotoxin binding to receptors on macrophages and other cells generates IL-12, which inhibits IgE responses. It also generates cytokines like IL-1, TNF-alpha, and IL-8, which cause inflammation. These signal transduction pathways resemble those leading to the generation of cytokines, such as IL-4, IL-13, and IL-5, which are responsible for the inflammation of IgE-mediated allergic disease. The main difference seems to be that endotoxin recruits neutrophils, but IgE recruits eosinophils, and the details of the tissue injury from these granulocytes differ. Sources of airborne endotoxin include many agricultural dusts, aerosols from contaminated water in many industrial plants, contaminated heating and air-conditioning systems, mist-generating humidifiers, and damp or water-damaged homes. Acute inhalation of high concentrations of endotoxin can cause fever, cough, and dyspnea. Chronic inhalation of lesser amounts causes chronic bronchitis and emphysema and is associated with airway hyperresponsiveness. Airborne endotoxin adversely affects patients with asthma in 3 ways: (1) by increasing the severity of the airway inflammation; (2) by increasing the susceptibility to rhinovirus-induced colds; and (3) by causing chronic bronchitis and emphysema with development of irreversible airway obstruction after chronic exposure of adults. The most effective management is mitigating exposure. The potential of drug treatments requires further clinical investigation.. airway inflammation| asthma| cell biology| chronic obstructive pulmonary disease| endotoxin| eosinophils| environmental exposure neutrophils| tolerance|tumor-necrosis-factor| acute lung injury| nf-kappa-b| causes bronchial hyperresponsiveness| resolution computed-tomography| dose-response relationships| platelet-activating-factor| protein-tyrosine kinase| cotton textile workers| tnf-alpha production.	AUG-2001	airway inflammation| asthma| cell biology| chronic obstructive pulmonary disease| endotoxin| eosinophils| environmental exposure neutrophils| tolerance|tumor-necrosis-factor| acute lung injury| nf-kappa-b| causes bronchial hyperresponsiveness| resolution computed-tomography| dose-response relationships| platelet-activating-factor| protein-tyrosine kinase| cotton textile workers| tnf-alpha production	Reed, CE; Milton, DK	Endotoxin-stimulated innate immunity: A contributing factor for asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	airway inflammation; asthma; cell biology; chronic obstructive pulmonary disease; endotoxin; eosinophils; environmental exposure neutrophils; tolerance	TUMOR-NECROSIS-FACTOR; ACUTE LUNG INJURY; NF-KAPPA-B; CAUSES BRONCHIAL HYPERRESPONSIVENESS; RESOLUTION COMPUTED-TOMOGRAPHY; DOSE-RESPONSE RELATIONSHIPS; PLATELET-ACTIVATING-FACTOR; PROTEIN-TYROSINE KINASE; COTTON TEXTILE WORKERS; TNF-ALPHA PRODUCTION	Exposure to airborne endotoxin in infancy may protect against asthma by promoting enhanced T(H)1 response and tolerance to allergens. On the other hand, later in life, it adversely affects patients with asthma. Endotoxin binding to receptors on macrophages and other cells generates IL-12, which inhibits IgE responses. It also generates cytokines like IL-1, TNF-alpha, and IL-8, which cause inflammation. These signal transduction pathways resemble those leading to the generation of cytokines, such as IL-4, IL-13, and IL-5, which are responsible for the inflammation of IgE-mediated allergic disease. The main difference seems to be that endotoxin recruits neutrophils, but IgE recruits eosinophils, and the details of the tissue injury from these granulocytes differ. Sources of airborne endotoxin include many agricultural dusts, aerosols from contaminated water in many industrial plants, contaminated heating and air-conditioning systems, mist-generating humidifiers, and damp or water-damaged homes. Acute inhalation of high concentrations of endotoxin can cause fever, cough, and dyspnea. Chronic inhalation of lesser amounts causes chronic bronchitis and emphysema and is associated with airway hyperresponsiveness. Airborne endotoxin adversely affects patients with asthma in 3 ways: (1) by increasing the severity of the airway inflammation; (2) by increasing the susceptibility to rhinovirus-induced colds; and (3) by causing chronic bronchitis and emphysema with development of irreversible airway obstruction after chronic exposure of adults. The most effective management is mitigating exposure. The potential of drug treatments requires further clinical investigation.	185	146	2001	10	10.1067/mai.2001.116862	Allergy; Immunology
The potential impacts of climate variability and change on air pollution-related health effects in the United States. Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor. wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects.. air pollution| climate change| criteria air pollutants| global warming| ozone| particulate matter|southern california communities| obstructive pulmonary-disease| 0.12 ppm ozone| hospital admissions| nitrogen-dioxide| respiratory morbidity| exercising children| chronic exposure| differing levels| ucla population.	MAY-2001	air pollution| climate change| criteria air pollutants| global warming| ozone| particulate matter|southern california communities| obstructive pulmonary-disease| 0.12 ppm ozone| hospital admissions| nitrogen-dioxide| respiratory morbidity| exercising children| chronic exposure| differing levels| ucla population	Bernard, SM; Samet, JM; Grambsch, A; Ebi, KL; Romieu, I	The potential impacts of climate variability and change on air pollution-related health effects in the United States		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; climate change; criteria air pollutants; global warming; ozone; particulate matter	SOUTHERN CALIFORNIA COMMUNITIES; OBSTRUCTIVE PULMONARY-DISEASE; 0.12 PPM OZONE; HOSPITAL ADMISSIONS; NITROGEN-DIOXIDE; RESPIRATORY MORBIDITY; EXERCISING CHILDREN; CHRONIC EXPOSURE; DIFFERING LEVELS; UCLA POPULATION	Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor. wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects.	81	146	2001	11	10.2307/3435010	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
An Unexpected Role for Uric Acid as an Inducer of T Helper 2 Cell Immunity to Inhaled Antigens and Inflammatory Mediator of Allergic Asthma. Although deposition of uric acid (UA) crystals is known as the cause of gout, it is unclear whether UA plays a role in other inflammatory diseases. We here have shown that UA is released in the airways of allergen-challenged asthmatic patients and mice, where it was necessary for mounting T helper 2 (Th2) cell immunity, airway eosinophilia, and bronchial hyperreactivity to inhaled harmless proteins and clinically relevant house dust mite allergen. Conversely, administration of UA crystals together with protein antigen was sufficient to promote Th2 cell immunity and features of asthma. The adjuvant effects of UA did not require the inflammasome (NIrp3, Pycard) or the interleukin-1 (Myd88, IL-1r) axis. UA crystals promoted Th2 cell immunity by activating dendritic cells through spleen tyrosine kinase and PI3-kinase delta signaling. These findings provide further molecular insight into Th2 cell development and identify UA as an essential initiator and amplifier of allergic inflammation.. house-dust mite| induced neutrophil activation| monosodium urate crystals| helper type-2 response| cd4(+) t-cells| dendritic cells| airway inflammation| nalp3 inflammasome| xanthine-oxidase| adaptive immunity.	APR 22-2011	house-dust mite| induced neutrophil activation| monosodium urate crystals| helper type-2 response| cd4(+) t-cells| dendritic cells| airway inflammation| nalp3 inflammasome| xanthine-oxidase| adaptive immunity	Kool, M; Willart, MAM; van Nimwegen, M; Bergen, I; Pouliot, P; Virchow, JC; Rogers, N; Osorio, F; Reis e Sousa, C; Hammad, H; Lambrecht, BN	An Unexpected Role for Uric Acid as an Inducer of T Helper 2 Cell Immunity to Inhaled Antigens and Inflammatory Mediator of Allergic Asthma		IMMUNITY		HOUSE-DUST MITE; INDUCED NEUTROPHIL ACTIVATION; MONOSODIUM URATE CRYSTALS; HELPER TYPE-2 RESPONSE; CD4(+) T-CELLS; DENDRITIC CELLS; AIRWAY INFLAMMATION; NALP3 INFLAMMASOME; XANTHINE-OXIDASE; ADAPTIVE IMMUNITY	Although deposition of uric acid (UA) crystals is known as the cause of gout, it is unclear whether UA plays a role in other inflammatory diseases. We here have shown that UA is released in the airways of allergen-challenged asthmatic patients and mice, where it was necessary for mounting T helper 2 (Th2) cell immunity, airway eosinophilia, and bronchial hyperreactivity to inhaled harmless proteins and clinically relevant house dust mite allergen. Conversely, administration of UA crystals together with protein antigen was sufficient to promote Th2 cell immunity and features of asthma. The adjuvant effects of UA did not require the inflammasome (NIrp3, Pycard) or the interleukin-1 (Myd88, IL-1r) axis. UA crystals promoted Th2 cell immunity by activating dendritic cells through spleen tyrosine kinase and PI3-kinase delta signaling. These findings provide further molecular insight into Th2 cell development and identify UA as an essential initiator and amplifier of allergic inflammation.	55	145	2011	14	10.1016/j.immuni.2011.03.015	Immunology
Asthma in older adults. Asthma in older people is common and is characterised by underdiagnosis and undertreatment. Ageing is associated with unique issues that modify expression, recognition, and treatment of the disease. In particular, asthma and chronic obstructive pulmonary disease (COPD) both overlap and converge in older people. This concurrence, together with absence of precise diagnostic methods, makes diagnosis complex. A multidimensional assessment that addresses airway problems, comorbidities, risk factors, and management skills will draw attention to key needs for intervention. Increased attention to the complications of asthma and obstructive airway disease in older people is needed, specifically to develop effective systems of care, appropriate clinical practice guidelines, and a research agenda that delivers improved health outcomes.. obstructive pulmonary-disease| randomized controlled-trials| air-flow obstruction| dry powder inhalers| quality-of-care| smoking-cessation| elderly-patients| geriatric assessment| comorbid conditions| practice guidelines.	SEP 4-2010	obstructive pulmonary-disease| randomized controlled-trials| air-flow obstruction| dry powder inhalers| quality-of-care| smoking-cessation| elderly-patients| geriatric assessment| comorbid conditions| practice guidelines	Gibson, PG; McDonald, VM; Marks, GB	Asthma in older adults		LANCET		OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIALS; AIR-FLOW OBSTRUCTION; DRY POWDER INHALERS; QUALITY-OF-CARE; SMOKING-CESSATION; ELDERLY-PATIENTS; GERIATRIC ASSESSMENT; COMORBID CONDITIONS; PRACTICE GUIDELINES	Asthma in older people is common and is characterised by underdiagnosis and undertreatment. Ageing is associated with unique issues that modify expression, recognition, and treatment of the disease. In particular, asthma and chronic obstructive pulmonary disease (COPD) both overlap and converge in older people. This concurrence, together with absence of precise diagnostic methods, makes diagnosis complex. A multidimensional assessment that addresses airway problems, comorbidities, risk factors, and management skills will draw attention to key needs for intervention. Increased attention to the complications of asthma and obstructive airway disease in older people is needed, specifically to develop effective systems of care, appropriate clinical practice guidelines, and a research agenda that delivers improved health outcomes.	105	145	2010	11	10.1016/S0140-6736(10)61087-2	General & Internal Medicine
Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy. Background: The diversity in the perceived prevalence, recovery, and risk factors for cow's milk allergy (CMA) necessitated a large-scale, population-based prospective study. Objective: We sought to determine the prevalence, cross-reactivity with soy allergy, and risk factors for the development of CMA. Methods: In a prospective study the feeding history of 13,019 infants was obtained by means of telephone interview (95.8%) or questionnaire (4.2%). Infants with probable adverse reactions to milk were examined, skin prick tested, and challenged orally. Results: Ninety-eight percent of the cohort participated in the study. The cumulative incidence for IgE-mediated CMA was 0.5% (66/13,019 patients). The mean age of cow's milk protein (CMP) introduction was significantly different (P<.001) between the healthy infants (61.6 +/- 92.5 days) and those with IgE-mediated CMA (116.1 +/- 64.9 days). Only 0.05% of the infants who were started on regular CMP formula within the first 14 days versus 1.75% who were started on formula between the ages of 105 and 194 days had IgE-mediated CMA (P<.001). The odds ratio was 19.3 (95% CI, 6.0-62.1) for development of IgE-mediated CMA among infants with exposure to CMP at the age of 15 days or more (P<.001). Sixty-four patients with IgE-mediated CMA tolerated soy, and none had a proved allergy to soy. Conclusions: IgE-mediated CMA is much less common than generally reported. Early exposure to CMP as a supplement to breast-feeding might promote tolerance. Finally, soy is a reasonable feeding alternative in patients with IgE-mediated CMA. (J Allergy Clin Immunol 2010;126:77-82.). ige-mediated cow's milk allergy| soy allergy| breast-feeding| skin prick test| oral challenge|koala birth cohort| food challenges| peanut allergy| infants| immediate| children| age| hypersensitivity| consumption| childhood.	JUL-2010	ige-mediated cow's milk allergy| soy allergy| breast-feeding| skin prick test| oral challenge|koala birth cohort| food challenges| peanut allergy| infants| immediate| children| age| hypersensitivity| consumption| childhood	Katz, Y; Rajuan, N; Goldberg, MR; Eisenberg, E; Heyman, E; Cohen, A; Leshno, M	Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	IgE-mediated cow's milk allergy; soy allergy; breast-feeding; skin prick test; oral challenge	KOALA BIRTH COHORT; FOOD CHALLENGES; PEANUT ALLERGY; INFANTS; IMMEDIATE; CHILDREN; AGE; HYPERSENSITIVITY; CONSUMPTION; CHILDHOOD	Background: The diversity in the perceived prevalence, recovery, and risk factors for cow's milk allergy (CMA) necessitated a large-scale, population-based prospective study. Objective: We sought to determine the prevalence, cross-reactivity with soy allergy, and risk factors for the development of CMA. Methods: In a prospective study the feeding history of 13,019 infants was obtained by means of telephone interview (95.8%) or questionnaire (4.2%). Infants with probable adverse reactions to milk were examined, skin prick tested, and challenged orally. Results: Ninety-eight percent of the cohort participated in the study. The cumulative incidence for IgE-mediated CMA was 0.5% (66/13,019 patients). The mean age of cow's milk protein (CMP) introduction was significantly different (P<.001) between the healthy infants (61.6 +/- 92.5 days) and those with IgE-mediated CMA (116.1 +/- 64.9 days). Only 0.05% of the infants who were started on regular CMP formula within the first 14 days versus 1.75% who were started on formula between the ages of 105 and 194 days had IgE-mediated CMA (P<.001). The odds ratio was 19.3 (95% CI, 6.0-62.1) for development of IgE-mediated CMA among infants with exposure to CMP at the age of 15 days or more (P<.001). Sixty-four patients with IgE-mediated CMA tolerated soy, and none had a proved allergy to soy. Conclusions: IgE-mediated CMA is much less common than generally reported. Early exposure to CMP as a supplement to breast-feeding might promote tolerance. Finally, soy is a reasonable feeding alternative in patients with IgE-mediated CMA. (J Allergy Clin Immunol 2010;126:77-82.)	36	145	2010	6	10.1016/j.jaci.2010.04.020	Allergy; Immunology
SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production. Various acute and chronic inflammatory stimuli increase the number and activity of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess mucus production are central to the pathogenesis of chronic pulmonary diseases. However, little is known about the transcriptional programs that regulate goblet cell differentiation. Here, we show that SAM-pointed domain-containing Ets-like factor (SPDEF) controls a transcriptional program critical for pulmonary goblet cell differentiation in mice. Initial cell-lineage-tracing analysis identified nonciliated secretory epithelial cells, known as Clara cells, as the progenitors of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell differentiation in the absence of cell proliferation. This was associated with enhanced expression of genes regulating goblet cell differentiation and protein glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and glucosaminyl. (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after sensitization with pulmonary allergen, and the proteins were colocalized in goblet cells lining the airways of patients with chronic lung diseases. Deletion of the mouse Spdef gene resulted in the absence of goblet cells in tracheal/laryngeal submucosal glands and in the conducting airway epithelium after pulmonary allergen exposure in vivo. These data show that SPDEF plays a critical role in regulating a transcriptional network mediating the goblet cell differentiation and mucus hyperproduction associated with chronic pulmonary disorders.. bronchial epithelial-cells| transcription factor| human airway| lung morphogenesis| mucin biosynthesis| expression| receptor| asthma| growth| il-13.	OCT-2009	bronchial epithelial-cells| transcription factor| human airway| lung morphogenesis| mucin biosynthesis| expression| receptor| asthma| growth| il-13	Chen, G; Korfhagen, TR; Xu, Y; Kitzmiller, J; Wert, SE; Maeda, Y; Gregorieff, A; Clevers, H; Whitsett, JA	SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production		JOURNAL OF CLINICAL INVESTIGATION		BRONCHIAL EPITHELIAL-CELLS; TRANSCRIPTION FACTOR; HUMAN AIRWAY; LUNG MORPHOGENESIS; MUCIN BIOSYNTHESIS; EXPRESSION; RECEPTOR; ASTHMA; GROWTH; IL-13	Various acute and chronic inflammatory stimuli increase the number and activity of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess mucus production are central to the pathogenesis of chronic pulmonary diseases. However, little is known about the transcriptional programs that regulate goblet cell differentiation. Here, we show that SAM-pointed domain-containing Ets-like factor (SPDEF) controls a transcriptional program critical for pulmonary goblet cell differentiation in mice. Initial cell-lineage-tracing analysis identified nonciliated secretory epithelial cells, known as Clara cells, as the progenitors of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell differentiation in the absence of cell proliferation. This was associated with enhanced expression of genes regulating goblet cell differentiation and protein glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and glucosaminyl. (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after sensitization with pulmonary allergen, and the proteins were colocalized in goblet cells lining the airways of patients with chronic lung diseases. Deletion of the mouse Spdef gene resulted in the absence of goblet cells in tracheal/laryngeal submucosal glands and in the conducting airway epithelium after pulmonary allergen exposure in vivo. These data show that SPDEF plays a critical role in regulating a transcriptional network mediating the goblet cell differentiation and mucus hyperproduction associated with chronic pulmonary disorders.	60	145	2009	11	10.1172/JCI39731	Research & Experimental Medicine
Asthma and Posttraumatic Stress Symptoms 5 to 6 Years Following Exposure to the World Trade Center Terrorist Attack. Context The World Trade Center Health Registry provides a unique opportunity to examine long-term health effects of a large-scale disaster. Objective To examine risk factors for new asthma diagnoses and event-related post-traumatic stress (PTS) symptoms among exposed adults 5 to 6 years following exposure to the September 11, 2001, World Trade Center (WTC) terrorist attack. Design, Setting, and Participants Longitudinal cohort study with wave 1 (W1) enrollment of 71 437 adults in 2003-2004, including rescue/recovery worker, lower Manhattan resident, lower Manhattan office worker, and passersby eligibility groups; 46 322 adults (68%) completed the wave 2 (W2) survey in 2006-2007. Main Outcome Measures Self-reported diagnosed asthma following September 11; event-related current PTS symptoms indicative of probable posttraumatic stress disorder (PTSD), assessed using the PTSD Checklist (cutoff score >= 44). Results Of W2 participants with no stated asthma history, 10.2% (95% confidence interval [CI], 9.9%-10.5%) reported new asthma diagnoses postevent. Intense dust cloud exposure on September 11 was a major contributor to new asthma diagnoses for all eligibility groups: for example, 19.1% vs 9.6% in those without exposure among rescue/recovery workers (adjusted odds ratio, 1.5 [ 95% CI, 1.4-1.7]). Asthma risk was highest among rescue/recovery workers on the WTC pile on September 11 (20.5% [ 95% CI, 19.0%-22.0%]). Persistent risks included working longer at the WTC site, not evacuating homes, and experiencing a heavy layer of dust in home or office. Of participants with no PTSD history, 23.8% ( 95% CI, 23.4%-24.2%) reported PTS symptoms at either W1(14.3%) or W2 (19.1%). Nearly 10% ( 9.6% [ 95% CI, 9.3%-9.8%]) had PTS symptoms at both surveys, 4.7% ( 95% CI, 4.5%-4.9%) had PTS symptoms at W1 only, and 9.5% ( 95% CI, 9.3%-9.8%) had PTS symptoms at W2 only. At W2, passersby had the highest rate of PTS symptoms (23.2% [ 95% CI, 21.4%-25.0%]). Event-related loss of spouse or job was associated with PTS symptoms at W2. Conclusion Acute and prolonged exposures were both associated with a large burden of asthma and PTS symptoms 5 to 6 years after the September 11 WTC attack. JAMA. 2009;302(5):502-516 www.jama.com. new-york-city| center health registry| disaster victims speak| 11 september 2001| psychometric properties| respiratory symptoms| recovery workers| ptsd checklist| risk-factors| center site.	AUG 5-2009	new-york-city| center health registry| disaster victims speak| 11 september 2001| psychometric properties| respiratory symptoms| recovery workers| ptsd checklist| risk-factors| center site	Brackbill, RM; Hadler, JL; DiGrande, L; Ekenga, CC; Farfel, MR; Friedman, S; Perlman, SE; Stellman, SD; Walker, DJ; Wu, D; Yu, SC; Thorpe, LE	Asthma and Posttraumatic Stress Symptoms 5 to 6 Years Following Exposure to the World Trade Center Terrorist Attack		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		NEW-YORK-CITY; CENTER HEALTH REGISTRY; DISASTER VICTIMS SPEAK; 11 SEPTEMBER 2001; PSYCHOMETRIC PROPERTIES; RESPIRATORY SYMPTOMS; RECOVERY WORKERS; PTSD CHECKLIST; RISK-FACTORS; CENTER SITE	Context The World Trade Center Health Registry provides a unique opportunity to examine long-term health effects of a large-scale disaster. Objective To examine risk factors for new asthma diagnoses and event-related post-traumatic stress (PTS) symptoms among exposed adults 5 to 6 years following exposure to the September 11, 2001, World Trade Center (WTC) terrorist attack. Design, Setting, and Participants Longitudinal cohort study with wave 1 (W1) enrollment of 71 437 adults in 2003-2004, including rescue/recovery worker, lower Manhattan resident, lower Manhattan office worker, and passersby eligibility groups; 46 322 adults (68%) completed the wave 2 (W2) survey in 2006-2007. Main Outcome Measures Self-reported diagnosed asthma following September 11; event-related current PTS symptoms indicative of probable posttraumatic stress disorder (PTSD), assessed using the PTSD Checklist (cutoff score >= 44). Results Of W2 participants with no stated asthma history, 10.2% (95% confidence interval [CI], 9.9%-10.5%) reported new asthma diagnoses postevent. Intense dust cloud exposure on September 11 was a major contributor to new asthma diagnoses for all eligibility groups: for example, 19.1% vs 9.6% in those without exposure among rescue/recovery workers (adjusted odds ratio, 1.5 [ 95% CI, 1.4-1.7]). Asthma risk was highest among rescue/recovery workers on the WTC pile on September 11 (20.5% [ 95% CI, 19.0%-22.0%]). Persistent risks included working longer at the WTC site, not evacuating homes, and experiencing a heavy layer of dust in home or office. Of participants with no PTSD history, 23.8% ( 95% CI, 23.4%-24.2%) reported PTS symptoms at either W1(14.3%) or W2 (19.1%). Nearly 10% ( 9.6% [ 95% CI, 9.3%-9.8%]) had PTS symptoms at both surveys, 4.7% ( 95% CI, 4.5%-4.9%) had PTS symptoms at W1 only, and 9.5% ( 95% CI, 9.3%-9.8%) had PTS symptoms at W2 only. At W2, passersby had the highest rate of PTS symptoms (23.2% [ 95% CI, 21.4%-25.0%]). Event-related loss of spouse or job was associated with PTS symptoms at W2. Conclusion Acute and prolonged exposures were both associated with a large burden of asthma and PTS symptoms 5 to 6 years after the September 11 WTC attack. JAMA. 2009;302(5):502-516 www.jama.com	52	145	2009	15		General & Internal Medicine
"Respiratory health and individual estimated exposure to traffic-related air pollutants in a cohort of young children. Objectives: To estimate long-term exposure to traffic-related air pollutants on an individual basis and to assess adverse health effects using a combination of air pollution measurement data, data from geographical information systems (GIS) and questionnaire data. Methods: 40 measurement sites in the city of Munich, Germany were selected at which to collect particulate matter with a 50% cut-off aerodynamic diameter of 2.5 mm (PM2.5) and to measure PM2.5 absorbance and nitrogen dioxide (NO2). A pool of GIS variables (information about street length, household and population density and land use) was collected for the Munich metropolitan area and was used in multiple linear regression models to predict traffic-related air pollutants. These models were also applied to the birth addresses of two birth cohorts (German Infant Nutritional Intervention Study (GINI) and Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany (LISA)) in the Munich metropolitan area. Associations between air pollution concentrations at birth address and 1-year and 2-year incidences of respiratory symptoms were analysed. Results: The following means for the estimated exposures to PM2.5, PM2.5 absorbance and NO2 were obtained: 12.8 mu g/m(3), 1.7 x 10(-5) m(-1) and 35.3 mu g/m(3), respectively. Adjusted odds ratios (ORs) for wheezing, cough without infection, dry cough at night, bronchial asthma, bronchitis and respiratory infections indicated positive associations with traffic-related air pollutants. After controlling for individual confounders, significant associations were found between the pollutant PM2.5 and sneezing, runny/stuffed nose during the first year of life (OR 1.16, 95% confidence interval 1.01 to 1.34) Similar effects were observed for the second year of life. These findings are similar to those from our previous analysis that were restricted to a subcohort in Munich city. The extended study also showed significant effects for sneezing, running/stuffed nose. Additionally, significant associations were found between NO2 and dry cough at night (or bronchitis) during the first year of life. The variable ""living close to major roads'' (< 50 m), which was not analysed for the previous inner city cohort with birth addresses in the city of Munich, turned out to increase the risk of wheezing and asthmatic/spastic/obstructive bronchitis. Conclusions: Effects on asthma and hay fever are subject to confirmation at older ages, when these outcomes can be more validly assessed.. particulate matter| preschool-children| atopic-dermatitis| nitrogen-dioxide| birth cohort| pollution| asthma| symptoms| association| gis."	JAN-2007	particulate matter| preschool-children| atopic-dermatitis| nitrogen-dioxide| birth cohort| pollution| asthma| symptoms| association| gis	Morgenstern, V; Zutavern, A; Cyrys, J; Brockow, I; Gehring, U; Koletzko, S; Bauer, CP; Reinhardt, D; Wichmann, HE; Heinrich, J	Respiratory health and individual estimated exposure to traffic-related air pollutants in a cohort of young children		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		PARTICULATE MATTER; PRESCHOOL-CHILDREN; ATOPIC-DERMATITIS; NITROGEN-DIOXIDE; BIRTH COHORT; POLLUTION; ASTHMA; SYMPTOMS; ASSOCIATION; GIS	"Objectives: To estimate long-term exposure to traffic-related air pollutants on an individual basis and to assess adverse health effects using a combination of air pollution measurement data, data from geographical information systems (GIS) and questionnaire data. Methods: 40 measurement sites in the city of Munich, Germany were selected at which to collect particulate matter with a 50% cut-off aerodynamic diameter of 2.5 mm (PM2.5) and to measure PM2.5 absorbance and nitrogen dioxide (NO2). A pool of GIS variables (information about street length, household and population density and land use) was collected for the Munich metropolitan area and was used in multiple linear regression models to predict traffic-related air pollutants. These models were also applied to the birth addresses of two birth cohorts (German Infant Nutritional Intervention Study (GINI) and Influence of Life-style factors on the development of the Immune System and Allergies in East and West Germany (LISA)) in the Munich metropolitan area. Associations between air pollution concentrations at birth address and 1-year and 2-year incidences of respiratory symptoms were analysed. Results: The following means for the estimated exposures to PM2.5, PM2.5 absorbance and NO2 were obtained: 12.8 mu g/m(3), 1.7 x 10(-5) m(-1) and 35.3 mu g/m(3), respectively. Adjusted odds ratios (ORs) for wheezing, cough without infection, dry cough at night, bronchial asthma, bronchitis and respiratory infections indicated positive associations with traffic-related air pollutants. After controlling for individual confounders, significant associations were found between the pollutant PM2.5 and sneezing, runny/stuffed nose during the first year of life (OR 1.16, 95% confidence interval 1.01 to 1.34) Similar effects were observed for the second year of life. These findings are similar to those from our previous analysis that were restricted to a subcohort in Munich city. The extended study also showed significant effects for sneezing, running/stuffed nose. Additionally, significant associations were found between NO2 and dry cough at night (or bronchitis) during the first year of life. The variable ""living close to major roads'' (< 50 m), which was not analysed for the previous inner city cohort with birth addresses in the city of Munich, turned out to increase the risk of wheezing and asthmatic/spastic/obstructive bronchitis. Conclusions: Effects on asthma and hay fever are subject to confirmation at older ages, when these outcomes can be more validly assessed."	39	145	2007	9	10.1136/oem.2006.028241	Public, Environmental & Occupational Health
Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism. It is now well established that passive exposure to inhaled OVA leads to a state of immunological tolerance. Therefore, to elicit allergic sensitization, researchers have been compelled to devise alternative strategies, such as the systemic delivery of OVA in the context of powerful adjuvants, which are alien to the way humans are exposed and sensitized to allergens. The objectives of these studies were to investigate immune-inflammatory responses to intranasal delivery of a purified house dust mite (HDM) extract and to evaluate the role of GM-CSF in this process. HDM was delivered to BALB/c mice daily for 10 days. After the last exposure, mice were killed, bronchoalveolar lavage was performed, and samples were obtained. Expression/production of Th2-associated molecules in the lymph nodes, lung, and spleen were evaluated by real-time quantitative PCR and ELISA, respectively. Using this exposure protocol, exposure to HDM alone generated Th2 sensitization based on the expression/production of Th2 effector molecules and airway eosinophilic inflammation. Flow cytometric analysis demonstrated expansion and activation of APCs in the lung and an influx of activated Th2 effector cells. Moreover, this inflammation was accompanied by airways hyper-responsiveness and a robust memory-driven immune response. Finally, administration of anti-GM-CSF-neutralizing Abs markedly reduced immune-inflammatory responses in both lung and spleen. Thus, intranasal delivery of HDM results in Th2 sensitization and airway eosinophilic inflammation that appear to be mediated, at least in part, by endogenous GM-CSF production.. colony-stimulating factor| epithelial-cells| inhaled antigen| t-cell| sensitized mice| ige responses| model| hyperresponsiveness| eosinophilia| ovalbumin.	NOV 15-2004	colony-stimulating factor| epithelial-cells| inhaled antigen| t-cell| sensitized mice| ige responses| model| hyperresponsiveness| eosinophilia| ovalbumin	Cates, EC; Fattouh, R; Wattie, J; Inman, MD; Goncharova, S; Coyle, AJ; Gutierrez-Ramos, JC; Jordana, M	Intranasal exposure of mice to house dust mite elicits allergic airway inflammation via a GM-CSF-mediated mechanism		JOURNAL OF IMMUNOLOGY		COLONY-STIMULATING FACTOR; EPITHELIAL-CELLS; INHALED ANTIGEN; T-CELL; SENSITIZED MICE; IGE RESPONSES; MODEL; HYPERRESPONSIVENESS; EOSINOPHILIA; OVALBUMIN	It is now well established that passive exposure to inhaled OVA leads to a state of immunological tolerance. Therefore, to elicit allergic sensitization, researchers have been compelled to devise alternative strategies, such as the systemic delivery of OVA in the context of powerful adjuvants, which are alien to the way humans are exposed and sensitized to allergens. The objectives of these studies were to investigate immune-inflammatory responses to intranasal delivery of a purified house dust mite (HDM) extract and to evaluate the role of GM-CSF in this process. HDM was delivered to BALB/c mice daily for 10 days. After the last exposure, mice were killed, bronchoalveolar lavage was performed, and samples were obtained. Expression/production of Th2-associated molecules in the lymph nodes, lung, and spleen were evaluated by real-time quantitative PCR and ELISA, respectively. Using this exposure protocol, exposure to HDM alone generated Th2 sensitization based on the expression/production of Th2 effector molecules and airway eosinophilic inflammation. Flow cytometric analysis demonstrated expansion and activation of APCs in the lung and an influx of activated Th2 effector cells. Moreover, this inflammation was accompanied by airways hyper-responsiveness and a robust memory-driven immune response. Finally, administration of anti-GM-CSF-neutralizing Abs markedly reduced immune-inflammatory responses in both lung and spleen. Thus, intranasal delivery of HDM results in Th2 sensitization and airway eosinophilic inflammation that appear to be mediated, at least in part, by endogenous GM-CSF production.	30	145	2004	9		Immunology
The natural history of peanut allergy in young children and its association with serum peanut-specific IgE. Objectives: To observe the nature and frequency of adverse reactions caused by accidental peanut exposure in young children with clinical peanut hypersensitivity and to determine the value of serum peanut-specific IgE levels during follow-up. Study design: Eighty-three children with clinical peanut hypersensitivity diagnosed before their fourth birthdays were contacted yearly to track adverse peanut reactions. Serum peanut-specific IgE levels were determined in 51 of 83 subjects. Results: Fifty-eight percent (31/53) of subjects followed up for 5 years experienced adverse reactions from accidental peanut exposure, Regardless of the nature of their initial reaction, the majority with subsequent reactions (52%, 31/60) experienced potentially life-threatening symptoms. The group with isolated skin symptoms (11/51, 22%) had lower serum peanut-specific IgE levels than the group with respiratory and/or gastrointestinal symptoms (40/51, 78%) (median: 1.25 kU(A)/L vs 11.65 kU(A)/L, P = .004, Wilcoxon rank sums test). Despite this, there was no threshold level below which only skin symptoms appeared to occur. Four selected subjects had negative double-blind placebo-controlled food challenge responses to peanuts during follow-up. Conclusions: The majority of children with clinical peanut hypersensitivity followed up for 5 years will have adverse reactions from accidental peanut exposure. Symptoms experienced during subsequent adverse peanut reactions may not be consistent with symptoms reported during initial reactions. Therefore proper education regarding peanut avoidance land treatment of adverse reactions is necessary in all cases of clinical peanut hypersensitivity. Young children who are allergic to peanuts can lose clinical hypersensitivity.. cow milk allergy| food challenges| clinical course| double-blind| nut allergy| skin-tests| hypersensitivity| anaphylaxis| adolescents| infants.	DEC-2000	cow milk allergy| food challenges| clinical course| double-blind| nut allergy| skin-tests| hypersensitivity| anaphylaxis| adolescents| infants	Vander Leek, TK; Liu, AH; Stefanski, K; Blacker, B; Bock, SA	The natural history of peanut allergy in young children and its association with serum peanut-specific IgE		JOURNAL OF PEDIATRICS		COW MILK ALLERGY; FOOD CHALLENGES; CLINICAL COURSE; DOUBLE-BLIND; NUT ALLERGY; SKIN-TESTS; HYPERSENSITIVITY; ANAPHYLAXIS; ADOLESCENTS; INFANTS	Objectives: To observe the nature and frequency of adverse reactions caused by accidental peanut exposure in young children with clinical peanut hypersensitivity and to determine the value of serum peanut-specific IgE levels during follow-up. Study design: Eighty-three children with clinical peanut hypersensitivity diagnosed before their fourth birthdays were contacted yearly to track adverse peanut reactions. Serum peanut-specific IgE levels were determined in 51 of 83 subjects. Results: Fifty-eight percent (31/53) of subjects followed up for 5 years experienced adverse reactions from accidental peanut exposure, Regardless of the nature of their initial reaction, the majority with subsequent reactions (52%, 31/60) experienced potentially life-threatening symptoms. The group with isolated skin symptoms (11/51, 22%) had lower serum peanut-specific IgE levels than the group with respiratory and/or gastrointestinal symptoms (40/51, 78%) (median: 1.25 kU(A)/L vs 11.65 kU(A)/L, P = .004, Wilcoxon rank sums test). Despite this, there was no threshold level below which only skin symptoms appeared to occur. Four selected subjects had negative double-blind placebo-controlled food challenge responses to peanuts during follow-up. Conclusions: The majority of children with clinical peanut hypersensitivity followed up for 5 years will have adverse reactions from accidental peanut exposure. Symptoms experienced during subsequent adverse peanut reactions may not be consistent with symptoms reported during initial reactions. Therefore proper education regarding peanut avoidance land treatment of adverse reactions is necessary in all cases of clinical peanut hypersensitivity. Young children who are allergic to peanuts can lose clinical hypersensitivity.	23	145	2000	7	10.1067/mpd.2000.109376	Pediatrics
(1 -> 3)-beta-D-glucan and endotoxin in house dust and peak flow variability in children. House dust-associated bacterial endotoxins have been shown to be associated with asthma severity, and a similar role has been suggested for fungal (1-->3)-beta-D-glucans. In this study the relation between these agents and peak expiratory flow (PEF) variability was investigated in 148 children 7 to 11 yr of age of whom 50% had self- or parent-reported chronic respiratory symptoms. All children self-monitored twice daily their PEF for a period of 16 wk. Dust samples were collected from mattresses and from living room and bedroom floors, and endotoxin and (1-->3)-beta-D-glucan were measured in dust extracts. The relations with mean daily PEF variability (Ampl%mean) were investigated by linear regression analysis, adjusting for dust mite allergen levels, presence of pets, and type of floor cover. In unadjusted analyses the levels of both endotoxin and (1-->3)-beta-D-glucan per square meter of living room floor were significantly associated with PEF-variability (but not when expressed per gram of sampled dust), particularly in atopic children with asthma symptoms. Adjusted analyses showed the same association for (1-->3)-beta-D-glucan but not for endotoxin. Although no associations were found with microbial agent levels in bedroom floor or mattress dust, high levels of (1-->3)-beta-D-glucan in living room floor dust apparently increase PEF variability in asthmatic children.. respiratory symptoms| home dampness| airways inflammation| asthmatic symptoms| childhood asthma| mite allergen| exposure| health| molds| environments.	OCT-2000	respiratory symptoms| home dampness| airways inflammation| asthmatic symptoms| childhood asthma| mite allergen| exposure| health| molds| environments	Douwes, J; Zuidhof, A; Doekes, G; van der Zee, S; Wouters, I; Boezen, HM; Brunekreef, B	(1 -> 3)-beta-D-glucan and endotoxin in house dust and peak flow variability in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		RESPIRATORY SYMPTOMS; HOME DAMPNESS; AIRWAYS INFLAMMATION; ASTHMATIC SYMPTOMS; CHILDHOOD ASTHMA; MITE ALLERGEN; EXPOSURE; HEALTH; MOLDS; ENVIRONMENTS	House dust-associated bacterial endotoxins have been shown to be associated with asthma severity, and a similar role has been suggested for fungal (1-->3)-beta-D-glucans. In this study the relation between these agents and peak expiratory flow (PEF) variability was investigated in 148 children 7 to 11 yr of age of whom 50% had self- or parent-reported chronic respiratory symptoms. All children self-monitored twice daily their PEF for a period of 16 wk. Dust samples were collected from mattresses and from living room and bedroom floors, and endotoxin and (1-->3)-beta-D-glucan were measured in dust extracts. The relations with mean daily PEF variability (Ampl%mean) were investigated by linear regression analysis, adjusting for dust mite allergen levels, presence of pets, and type of floor cover. In unadjusted analyses the levels of both endotoxin and (1-->3)-beta-D-glucan per square meter of living room floor were significantly associated with PEF-variability (but not when expressed per gram of sampled dust), particularly in atopic children with asthma symptoms. Adjusted analyses showed the same association for (1-->3)-beta-D-glucan but not for endotoxin. Although no associations were found with microbial agent levels in bedroom floor or mattress dust, high levels of (1-->3)-beta-D-glucan in living room floor dust apparently increase PEF variability in asthmatic children.	38	145	2000	7		General & Internal Medicine; Respiratory System
Tiotropium improves lung function in patients with severe uncontrolled asthma: A randomized controlled trial. Background: Some patients with severe asthma remain symptomatic and obstructed despite maximal recommended treatment. Tiotropium, a long-acting inhaled anticholinergic agent, might be an effective bronchodilator in such patients. Objective: We sought to compare the efficacy and safety of 2 doses of tiotropium (5 and 10 mu g daily) administered through the Respimat inhaler with placebo as add-on therapy in patients with uncontrolled severe asthma (Asthma Control Questionnaire score, >= 1.5; postbronchodilator FEV(1), <= 80% of predicted value) despite maintenance treatment with at least a high-dose inhaled corticosteroid plus a long-acting beta(2)-agonist. Methods: This was a randomized, double-blind, crossover study with three 8-week treatment periods. The primary end point was peak FEV(1) at the end of each treatment period. Results: Of 107 randomized patients (54% female patients; mean, 55 years of age; postbronchodilator FEV(1), 65% of predicted value), 100 completed all periods. Peak FEV(1) was significantly higher with 5 mu g (difference, 139 mL; 95% CI, 96181 mL) and 10 mu g (difference, 170 mL; 95% CI, 128-213 mL) of tiotropium than with placebo (both P < .0001). There was no significant difference between the active doses. Trough FEV(1) at the end of the dosing interval was higher with tiotropium (5 mg: 86 mL [95% CI, 41-132 mL]; 10 mg: 113 mL [95% CI, 67-159 mL]; both P < .0004). Daily home peak expiratory flow measurements were higher with both tiotropium doses. There were no significant differences in asthma-related health status or symptoms. Adverse events were balanced across groups except for dry mouth, which was more common on 10 mu g of tiotropium. Conclusion: The addition of once-daily tiotropium to asthma treatment, including a high-dose inhaled corticosteroid plus a long-acting beta(2)-agonist, significantly improves lung function over 24 hours in patients with inadequately controlled, severe, persistent asthma. (J Allergy Clin Immunol 2011;128:308-14.). asthma| severe uncontrolled asthma| randomized controlled trial| anticholinergics| tiotropium|obstructive pulmonary-disease| copd patients| bromide| adults| efficacy.	AUG-2011	asthma| severe uncontrolled asthma| randomized controlled trial| anticholinergics| tiotropium|obstructive pulmonary-disease| copd patients| bromide| adults| efficacy	Kerstjens, HAM; Disse, B; Schroder-Babo, W; Bantje, TA; Gahlemann, M; Sigmund, R; Engel, M; van Noord, JA	Tiotropium improves lung function in patients with severe uncontrolled asthma: A randomized controlled trial		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Asthma; severe uncontrolled asthma; randomized controlled trial; anticholinergics; tiotropium	OBSTRUCTIVE PULMONARY-DISEASE; COPD PATIENTS; BROMIDE; ADULTS; EFFICACY	Background: Some patients with severe asthma remain symptomatic and obstructed despite maximal recommended treatment. Tiotropium, a long-acting inhaled anticholinergic agent, might be an effective bronchodilator in such patients. Objective: We sought to compare the efficacy and safety of 2 doses of tiotropium (5 and 10 mu g daily) administered through the Respimat inhaler with placebo as add-on therapy in patients with uncontrolled severe asthma (Asthma Control Questionnaire score, >= 1.5; postbronchodilator FEV(1), <= 80% of predicted value) despite maintenance treatment with at least a high-dose inhaled corticosteroid plus a long-acting beta(2)-agonist. Methods: This was a randomized, double-blind, crossover study with three 8-week treatment periods. The primary end point was peak FEV(1) at the end of each treatment period. Results: Of 107 randomized patients (54% female patients; mean, 55 years of age; postbronchodilator FEV(1), 65% of predicted value), 100 completed all periods. Peak FEV(1) was significantly higher with 5 mu g (difference, 139 mL; 95% CI, 96181 mL) and 10 mu g (difference, 170 mL; 95% CI, 128-213 mL) of tiotropium than with placebo (both P < .0001). There was no significant difference between the active doses. Trough FEV(1) at the end of the dosing interval was higher with tiotropium (5 mg: 86 mL [95% CI, 41-132 mL]; 10 mg: 113 mL [95% CI, 67-159 mL]; both P < .0004). Daily home peak expiratory flow measurements were higher with both tiotropium doses. There were no significant differences in asthma-related health status or symptoms. Adverse events were balanced across groups except for dry mouth, which was more common on 10 mu g of tiotropium. Conclusion: The addition of once-daily tiotropium to asthma treatment, including a high-dose inhaled corticosteroid plus a long-acting beta(2)-agonist, significantly improves lung function over 24 hours in patients with inadequately controlled, severe, persistent asthma. (J Allergy Clin Immunol 2011;128:308-14.)	26	144	2011	7	10.1016/j.jaci.2011.04.039	Allergy; Immunology
Exhaled Breath Profiling Enables Discrimination of Chronic Obstructive Pulmonary Disease and Asthma. Rationale Chronic obstructive pulmonary disease (COPD) and asthma can exhibit overlapping clinical features. Exhaled air contains volatile organic compounds (VOCs) that may qualify as noninvasive biomarkers. VOC profiles can be assessed using integrative analysis by electronic nose, resulting in exhaled molecular fingerprints (breathprints). Objectives: We hypothesized that breathprints by electronic nose can discriminate patients with COPD and asthma. Methods: Ninety subjects participated in a cross-sectional study: 30 patients with COPD (age, 61.6+/-9.3 years; FEV1, 1.72+/-0.69 L), 20 patients with asthma (age, 35.4+/-15.1 years; FEV1, 3.32+/-0.86 L), 20 nonsmoking control subjects (age, 56.7+/-9.3 years; FEV1, 3.44+/-0.76 L), and 20 smoking control subjects (age, 56.1+/-5.9 years; FEV1, 3.58+/-0.78). After 5 minutes of tidal breathing through an inspiratory VOC filter, an expiratory vital capacity was collected in a Tedlar bag and sampled by electronic nose. Breathprints were analyzed by discriminant analysis on principal component reduction resulting in cross-validated accuracy values (accuracy). Repeatability and reproducibility were assessed by measuring samples in duplicate by two devices. Measurements and Main Results: Breathprints from patients with asthma were separated from patients with COPD (accuracy 96%; P < 0.001), from nonsmoking control subjects (accuracy, 95%; P < 0.001), and from smoking control subjects (accuracy, 92.5%; P < 0.001). Exhaled breath profiles of patients with COPD partially overlapped with those of asymptomatic smokers (accuracy, 66%; P = 0.006). Measurements were repeatable and reproducible. Conclusions: Molecular profiling of exhaled air can distinguish patients with COPD and asthma and control subjects. Our data demonstrate a potential of electronic noses in the differential diagnosis of obstructive airway diseases and in the risk assessment in asymptomatic smokers. Clinical trial registered with www.trialregister.nI (NTR 1282).. biomarkers| diagnosis| electronic nose| exhaled breath| volatile organic compounds|electronic nose| lung-cancer| systemic inflammation| global strategy| copd| air| similarities| biomarkers| proteomics| mechanisms.	DEC 1-2009	biomarkers| diagnosis| electronic nose| exhaled breath| volatile organic compounds|electronic nose| lung-cancer| systemic inflammation| global strategy| copd| air| similarities| biomarkers| proteomics| mechanisms	Fens, N; Zwinderman, AH; van der Schee, MP; de Nijs, SB; Dijkers, E; Roldaan, AC; Cheung, D; Bel, EH; Sterk, PJ	Exhaled Breath Profiling Enables Discrimination of Chronic Obstructive Pulmonary Disease and Asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	biomarkers; diagnosis; electronic nose; exhaled breath; volatile organic compounds	ELECTRONIC NOSE; LUNG-CANCER; SYSTEMIC INFLAMMATION; GLOBAL STRATEGY; COPD; AIR; SIMILARITIES; BIOMARKERS; PROTEOMICS; MECHANISMS	Rationale Chronic obstructive pulmonary disease (COPD) and asthma can exhibit overlapping clinical features. Exhaled air contains volatile organic compounds (VOCs) that may qualify as noninvasive biomarkers. VOC profiles can be assessed using integrative analysis by electronic nose, resulting in exhaled molecular fingerprints (breathprints). Objectives: We hypothesized that breathprints by electronic nose can discriminate patients with COPD and asthma. Methods: Ninety subjects participated in a cross-sectional study: 30 patients with COPD (age, 61.6+/-9.3 years; FEV1, 1.72+/-0.69 L), 20 patients with asthma (age, 35.4+/-15.1 years; FEV1, 3.32+/-0.86 L), 20 nonsmoking control subjects (age, 56.7+/-9.3 years; FEV1, 3.44+/-0.76 L), and 20 smoking control subjects (age, 56.1+/-5.9 years; FEV1, 3.58+/-0.78). After 5 minutes of tidal breathing through an inspiratory VOC filter, an expiratory vital capacity was collected in a Tedlar bag and sampled by electronic nose. Breathprints were analyzed by discriminant analysis on principal component reduction resulting in cross-validated accuracy values (accuracy). Repeatability and reproducibility were assessed by measuring samples in duplicate by two devices. Measurements and Main Results: Breathprints from patients with asthma were separated from patients with COPD (accuracy 96%; P < 0.001), from nonsmoking control subjects (accuracy, 95%; P < 0.001), and from smoking control subjects (accuracy, 92.5%; P < 0.001). Exhaled breath profiles of patients with COPD partially overlapped with those of asymptomatic smokers (accuracy, 66%; P = 0.006). Measurements were repeatable and reproducible. Conclusions: Molecular profiling of exhaled air can distinguish patients with COPD and asthma and control subjects. Our data demonstrate a potential of electronic noses in the differential diagnosis of obstructive airway diseases and in the risk assessment in asymptomatic smokers. Clinical trial registered with www.trialregister.nI (NTR 1282).	45	144	2009	7	10.1164/rccm.200906-0939OC	General & Internal Medicine; Respiratory System
BSACI guidelines for the management of allergic and non-allergic rhinitis. This guidance for the management of patients with allergic and non-allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co-morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research.. allergen| allergy| antihistamine| anti-leukotriene| aspirin| asthma| bsaci| cat allergen| child| corticosteroid| cromoglicate| decongestant| guideline| house dust mite| ige| immunotherapy| ipratropium bromide| lactation| nitric oxide| occupational| pregnancy| rhinitis| rhinosinusitis| sinusitis| skin prick test| sublingual immunotherapy| surgery|aqueous nasal spray| leukotriene receptor antagonists| randomized controlled-trial| sublingual-swallow immunotherapy| placebo-controlled evaluation| grass-pollen immunotherapy| controlled clinical-trial| health-care workers| quality-of-life| double-blind.	JAN-2008	allergen| allergy| antihistamine| anti-leukotriene| aspirin| asthma| bsaci| cat allergen| child| corticosteroid| cromoglicate| decongestant| guideline| house dust mite| ige| immunotherapy| ipratropium bromide| lactation| nitric oxide| occupational| pregnancy| rhinitis| rhinosinusitis| sinusitis| skin prick test| sublingual immunotherapy| surgery|aqueous nasal spray| leukotriene receptor antagonists| randomized controlled-trial| sublingual-swallow immunotherapy| placebo-controlled evaluation| grass-pollen immunotherapy| controlled clinical-trial| health-care workers| quality-of-life| double-blind	Scadding, GK; Durlham, SR; Mirakian, R; Jones, NS; Leech, SC; Farooque, S; Ryan, D; Walker, SM; Clark, AT; Dixon, TA; Jolles, SRA; Siddique, N; Cullinan, P; Howarth, PH; Nasser, SM	BSACI guidelines for the management of allergic and non-allergic rhinitis		CLINICAL AND EXPERIMENTAL ALLERGY	allergen; allergy; antihistamine; anti-leukotriene; aspirin; asthma; BSACI; cat allergen; child; corticosteroid; cromoglicate; decongestant; guideline; house dust mite; IgE; immunotherapy; ipratropium bromide; lactation; nitric oxide; occupational; pregnancy; rhinitis; rhinosinusitis; sinusitis; skin prick test; sublingual immunotherapy; surgery	AQUEOUS NASAL SPRAY; LEUKOTRIENE RECEPTOR ANTAGONISTS; RANDOMIZED CONTROLLED-TRIAL; SUBLINGUAL-SWALLOW IMMUNOTHERAPY; PLACEBO-CONTROLLED EVALUATION; GRASS-POLLEN IMMUNOTHERAPY; CONTROLLED CLINICAL-TRIAL; HEALTH-CARE WORKERS; QUALITY-OF-LIFE; DOUBLE-BLIND	This guidance for the management of patients with allergic and non-allergic rhinitis has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and paediatricians practicing in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are clinical classification of rhinitis, aetiology, diagnosis, investigations and management including subcutaneous and sublingual immunotherapy. There are also special sections for children, co-morbid associations and pregnancy. Finally, we have made recommendations for potential areas of future research.	234	144	2008	24	10.1111/j.1365-2222.2007.02888.x	Allergy; Immunology
Timing of initial exposure to cereal grains and the risk of wheat allergy. OBJECTIVE. Early exposure to solid foods in infancy has been associated with the development of allergy. The aim of this study was to examine the association between cereal-grain exposures (wheat, barley, rye, oats) in the infant diet and development of wheat allergy. METHODS. A total of 1612 children were enrolled at birth and followed to the mean age of 4.7 years. Questionnaire data and dietary exposures were obtained at 3, 6, 9, 15, and 24 months and annually thereafter. The main outcome measure was parent report of wheat allergy. Children with celiac disease autoimmunity detected by tissue transglutaminase autoantibodies were excluded. Wheat-specific immunoglobulin E levels on children reported to have wheat allergy were obtained. RESULTS. Sixteen children (1%) reported wheat allergy. Children who were first exposed to cereals after 6 months of age had an increased risk of wheat allergy compared with children first exposed to cereals before 6 months of age ( after controlling for confounders including a family history of allergic disorders and history of food allergy before 6 months of age). All 4 children with detectable wheat-specific immunoglobulin E were first exposed to cereal grains after 6 months. A first-degree relative with asthma, eczema, or hives was also independently associated with an increased risk of wheat-allergy development. CONCLUSIONS. Delaying initial exposure to cereal grains until after 6 months may increase the risk of developing wheat allergy. These results do not support delaying introduction of cereal grains for the protection of food allergy.. food allergy| wheat| solid-food exposure and introduction (timing)| infant diet|food allergy| atopic sensitization| mucosal immunity| celiac-disease| follow-up| autoimmunity| prevention| children| asthma| hypersensitivity.	JUN-2006	food allergy| wheat| solid-food exposure and introduction (timing)| infant diet|food allergy| atopic sensitization| mucosal immunity| celiac-disease| follow-up| autoimmunity| prevention| children| asthma| hypersensitivity	Poole, JA; Barriga, K; Leung, DYM; Hoffman, M; Eisenbarth, GS; Rewers, M; Norris, JM	Timing of initial exposure to cereal grains and the risk of wheat allergy		PEDIATRICS	food allergy; wheat; solid-food exposure and introduction (timing); infant diet	FOOD ALLERGY; ATOPIC SENSITIZATION; MUCOSAL IMMUNITY; CELIAC-DISEASE; FOLLOW-UP; AUTOIMMUNITY; PREVENTION; CHILDREN; ASTHMA; HYPERSENSITIVITY	OBJECTIVE. Early exposure to solid foods in infancy has been associated with the development of allergy. The aim of this study was to examine the association between cereal-grain exposures (wheat, barley, rye, oats) in the infant diet and development of wheat allergy. METHODS. A total of 1612 children were enrolled at birth and followed to the mean age of 4.7 years. Questionnaire data and dietary exposures were obtained at 3, 6, 9, 15, and 24 months and annually thereafter. The main outcome measure was parent report of wheat allergy. Children with celiac disease autoimmunity detected by tissue transglutaminase autoantibodies were excluded. Wheat-specific immunoglobulin E levels on children reported to have wheat allergy were obtained. RESULTS. Sixteen children (1%) reported wheat allergy. Children who were first exposed to cereals after 6 months of age had an increased risk of wheat allergy compared with children first exposed to cereals before 6 months of age ( after controlling for confounders including a family history of allergic disorders and history of food allergy before 6 months of age). All 4 children with detectable wheat-specific immunoglobulin E were first exposed to cereal grains after 6 months. A first-degree relative with asthma, eczema, or hives was also independently associated with an increased risk of wheat-allergy development. CONCLUSIONS. Delaying initial exposure to cereal grains until after 6 months may increase the risk of developing wheat allergy. These results do not support delaying introduction of cereal grains for the protection of food allergy.	27	144	2006	8	10.1542/peds.2005-1803	Pediatrics
Maternal smoking in pregnancy, fetal development, and childhood asthma. Objectives. We examined the relationships among maternal smoking in pregnancy, fetal development, and the risk of asthma in childhood. Methods. We conducted a population-based cohort study, where all 58841 singleton births were followed for 7 years using nationwide registries. Results. Maternal smoking increased the risk of asthma (adjusted odds ratio = 1.35; 95% confidence interval = 1.13, 1.62 for high exposure). Low birthweight and preterm delivery increased the risk of asthma at the age of 7, whereas being small for gestational age did not. Conclusions. Maternal smoking in pregnancy increases the risk of asthma during the first 7 years of life, and only a small fraction of the effect seems to be mediated through fetal growth. (Am J Public Health. 2004;94:136-140).. environmental tobacco-smoke| low-birth-weight| family history| lung-function| respiratory-function| parental smoking| children| infants| health| life.	JAN-2004	environmental tobacco-smoke| low-birth-weight| family history| lung-function| respiratory-function| parental smoking| children| infants| health| life	Jaakkola, JJK; Gissler, M	Maternal smoking in pregnancy, fetal development, and childhood asthma		AMERICAN JOURNAL OF PUBLIC HEALTH		ENVIRONMENTAL TOBACCO-SMOKE; LOW-BIRTH-WEIGHT; FAMILY HISTORY; LUNG-FUNCTION; RESPIRATORY-FUNCTION; PARENTAL SMOKING; CHILDREN; INFANTS; HEALTH; LIFE	Objectives. We examined the relationships among maternal smoking in pregnancy, fetal development, and the risk of asthma in childhood. Methods. We conducted a population-based cohort study, where all 58841 singleton births were followed for 7 years using nationwide registries. Results. Maternal smoking increased the risk of asthma (adjusted odds ratio = 1.35; 95% confidence interval = 1.13, 1.62 for high exposure). Low birthweight and preterm delivery increased the risk of asthma at the age of 7, whereas being small for gestational age did not. Conclusions. Maternal smoking in pregnancy increases the risk of asthma during the first 7 years of life, and only a small fraction of the effect seems to be mediated through fetal growth. (Am J Public Health. 2004;94:136-140).	19	144	2004	5	10.2105/AJPH.94.1.136	Public, Environmental & Occupational Health
Air pollution and hospital admissions for respiratory conditions in Rome, Italy. Most of the evidence regarding the association between particulate air pollution and emergency room visits or hospital admissions for respiratory conditions and asthma comes from the USA. European time-series analyses have suggested that gaseous air pollutants are important determinants of acute hospitalization for respiratory conditions, at least as important as particulate mass. The association between daily mean levels of suspended particles and gaseous pollutants (sulphur dioxide, nitrogen dioxide, carbon monoxide, ozone) was examined. The daily emergency hospital admissions for respiratory conditions in the metropolitan area of Rome during 1995 - 1997,were also recorded. Daily counts of hospital admissions for total respiratory conditions (43 admissions .day(-1)), acute respiratory infections including pneumonia (18.day(-1)), chronic obstructive pulmonary disease (COPD) (13.day(-1)), and asthma (4.5.day(-1)) among residents of all ages and among children (0-14 yrs) were analysed, The generalized additive models included spline smooth functions of the day of study, mean temperature, mean humidity, influenza epidemics, and indicator variables for day of the week and holidays, Total respiratory admissions were significantly associated with same-da, level of NO2 (2.5%, increase per interquartile range (IQR) change, 22.3 mug.m(-3)) and CO (2.8% increase per IQR, 1.5 mg.m(-3)). No effect was found for particulate matter and SO2, whereas O-3 was associated with admissions only among children (lag 1, 5.5%, increase per IQR, 23.9 mug.m(3)). The effect of NO2 was stronger on acute respirator!, infections (lag 0, 4.0% increase) and on asthma among children (lag 1, 10.7% increase). The admissions for all ages for asthma and CORD were associated only with same-day level of CO (5.5% and 4.3% increase, respectively). Multipollutant models confirmed the role of CO on all respiratory admissions, including asthma and COPD, and that of NO2 on acute respiratory infections, Among children, O-3 remained a strong indicator of acute respiratory infections, Carbon monoxide and photochetnical pollutants (nitrogen dioxide, ozone) appear to he determinants of acute respiratory conditions in Rome, Since carbon monoxide and nitrogen dioxide are good indicators of combustion products from traffic related sources, the detected effect may be due to unmeasured fine and ultrafine particles.. air pollution| hospital admissions| respiratory disease| time-series|obstructive pulmonary-disease| minneapolis st-paul| urban air| european cities| aphea project| time-series| asthma| association| emergency| london.	JUN-2001	air pollution| hospital admissions| respiratory disease| time-series|obstructive pulmonary-disease| minneapolis st-paul| urban air| european cities| aphea project| time-series| asthma| association| emergency| london	Fusco, D; Forastiere, F; Michelozzi, P; Spadea, T; Ostro, B; Arca, M; Perucci, CA	Air pollution and hospital admissions for respiratory conditions in Rome, Italy		EUROPEAN RESPIRATORY JOURNAL	air pollution; hospital admissions; respiratory disease; time-series	OBSTRUCTIVE PULMONARY-DISEASE; MINNEAPOLIS ST-PAUL; URBAN AIR; EUROPEAN CITIES; APHEA PROJECT; TIME-SERIES; ASTHMA; ASSOCIATION; EMERGENCY; LONDON	Most of the evidence regarding the association between particulate air pollution and emergency room visits or hospital admissions for respiratory conditions and asthma comes from the USA. European time-series analyses have suggested that gaseous air pollutants are important determinants of acute hospitalization for respiratory conditions, at least as important as particulate mass. The association between daily mean levels of suspended particles and gaseous pollutants (sulphur dioxide, nitrogen dioxide, carbon monoxide, ozone) was examined. The daily emergency hospital admissions for respiratory conditions in the metropolitan area of Rome during 1995 - 1997,were also recorded. Daily counts of hospital admissions for total respiratory conditions (43 admissions .day(-1)), acute respiratory infections including pneumonia (18.day(-1)), chronic obstructive pulmonary disease (COPD) (13.day(-1)), and asthma (4.5.day(-1)) among residents of all ages and among children (0-14 yrs) were analysed, The generalized additive models included spline smooth functions of the day of study, mean temperature, mean humidity, influenza epidemics, and indicator variables for day of the week and holidays, Total respiratory admissions were significantly associated with same-da, level of NO2 (2.5%, increase per interquartile range (IQR) change, 22.3 mug.m(-3)) and CO (2.8% increase per IQR, 1.5 mg.m(-3)). No effect was found for particulate matter and SO2, whereas O-3 was associated with admissions only among children (lag 1, 5.5%, increase per IQR, 23.9 mug.m(3)). The effect of NO2 was stronger on acute respirator!, infections (lag 0, 4.0% increase) and on asthma among children (lag 1, 10.7% increase). The admissions for all ages for asthma and CORD were associated only with same-day level of CO (5.5% and 4.3% increase, respectively). Multipollutant models confirmed the role of CO on all respiratory admissions, including asthma and COPD, and that of NO2 on acute respiratory infections, Among children, O-3 remained a strong indicator of acute respiratory infections, Carbon monoxide and photochetnical pollutants (nitrogen dioxide, ozone) appear to he determinants of acute respiratory conditions in Rome, Since carbon monoxide and nitrogen dioxide are good indicators of combustion products from traffic related sources, the detected effect may be due to unmeasured fine and ultrafine particles.	39	144	2001	8	10.1183/09031936.01.00005501	Respiratory System
The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Gastroesophageal reflux is a potential trigger of asthma that may be clinically silent. This study examines the prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. This prospective cohort study evaluated 26 patients with stable asthma without reflux symptoms using esophageal manometry and 24-h esophageal pH testing. Gastroesophageal reflux was considered present if esophageal acid contact times were abnormal. Demographic variables were analyzed to determine if they predicted the presence of gastroesophageal reflux, Asthma patients with asymptomatic gastroesophageal reflux were compared with 30 age-matched asthma patients with symptomatic gastroesophageal reflux. The prevalence of abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms was 62% (16 of 26), Demographic variables did not predict abnormal 24-h esophageal pH tests in asthma patients with asymptomatic gastroesophageal reflux. Asthma patients with asymptomatic gastroesophageal reflux had higher amounts of proximal esophageal acid exposure (p < 0.05) compared with asthma patients with symptomatic gastroesophageal reflux. Because demographic variables do not predict abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms, 24-h esophageal pH testing is required. This study suggests that gastroesophageal reflux is present in asthma patients, even in the absence of esophageal symptoms.. placebo-controlled crossover| lower esophageal sphincter| chronic cough| double-blind| omeprazole| therapy| disease| diagnosis| pressure.	JUL-2000	placebo-controlled crossover| lower esophageal sphincter| chronic cough| double-blind| omeprazole| therapy| disease| diagnosis| pressure	Harding, SM; Guzzo, MR; Richter, JE	The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		PLACEBO-CONTROLLED CROSSOVER; LOWER ESOPHAGEAL SPHINCTER; CHRONIC COUGH; DOUBLE-BLIND; OMEPRAZOLE; THERAPY; DISEASE; DIAGNOSIS; PRESSURE	Gastroesophageal reflux is a potential trigger of asthma that may be clinically silent. This study examines the prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. This prospective cohort study evaluated 26 patients with stable asthma without reflux symptoms using esophageal manometry and 24-h esophageal pH testing. Gastroesophageal reflux was considered present if esophageal acid contact times were abnormal. Demographic variables were analyzed to determine if they predicted the presence of gastroesophageal reflux, Asthma patients with asymptomatic gastroesophageal reflux were compared with 30 age-matched asthma patients with symptomatic gastroesophageal reflux. The prevalence of abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms was 62% (16 of 26), Demographic variables did not predict abnormal 24-h esophageal pH tests in asthma patients with asymptomatic gastroesophageal reflux. Asthma patients with asymptomatic gastroesophageal reflux had higher amounts of proximal esophageal acid exposure (p < 0.05) compared with asthma patients with symptomatic gastroesophageal reflux. Because demographic variables do not predict abnormal 24-h esophageal pH tests in asthma patients without reflux symptoms, 24-h esophageal pH testing is required. This study suggests that gastroesophageal reflux is present in asthma patients, even in the absence of esophageal symptoms.	35	144	2000	6		General & Internal Medicine; Respiratory System
Mechanisms of allergen-specific immunotherapy: Multiple suppressor factors at work in immune tolerance to allergens. Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a desensitizing therapy for IgE-mediated allergic diseases and represents a potentially curative way of treatment. The mechanisms of action of AIT include the induction of very early desensitization of mast cells and basophils; generation of regulatory T and regulatory B (Breg) cell responses; regulation of IgE and IgG(4); decreases in numbers and activity of eosinophils and mast cells in mucosal allergic tissues; and decreases in the activity of basophils in circulation. Skewing of allergen-specific effector T and effector B cells to a regulatory phenotype appears as a key event in the course of AIT and normal immune response to allergens. Recently, inducible IL-10-secreting Breg cells were also demonstrated to contribute to allergen tolerance through suppression of effector T cells and selective induction of IgG4 isotype antibodies. Allergen-specific regulatory T and Breg cells orchestrate a general immunoregulatory activity, which can be summarized as suppression of cytokines from inflammatory dendritic cells; suppression of effector T(H)1, T(H)2, and T(H)17 cells; suppression of allergen-specific IgE and induction of IgG(4); and suppression of migration of mast cells, basophils, eosinophils, and effector T cells to tissues. A detailed knowledge of the mechanisms of AIT is not only important in designing the prevention and treatment of allergic diseases but might also find applications in the treatment of autoimmune diseases, organ transplantation, chronic infection, and cancer.. regulatory t cells| immunotherapy| ige| t cells| il-10| tgf-beta| allergen immunotherapy| t helper cells| immune tolerance| ige| igg| t cells| b cells| mast cells| basophils| eosinophils|regulatory t-cells| immunology/practall consensus report| eosinophil cationic protein| grass-pollen immunotherapy| transcription factor foxp3| toll-like receptors| house-dust mites| sublingual immunotherapy| tgf-beta| asthmatic-children.	MAR-2014	regulatory t cells| immunotherapy| ige| t cells| il-10| tgf-beta| allergen immunotherapy| t helper cells| immune tolerance| ige| igg| t cells| b cells| mast cells| basophils| eosinophils|regulatory t-cells| immunology/practall consensus report| eosinophil cationic protein| grass-pollen immunotherapy| transcription factor foxp3| toll-like receptors| house-dust mites| sublingual immunotherapy| tgf-beta| asthmatic-children	Akdis, M; Akdis, CA	Mechanisms of allergen-specific immunotherapy: Multiple suppressor factors at work in immune tolerance to allergens		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Regulatory T cells; immunotherapy; IgE; T cells; IL-10; TGF-beta; allergen immunotherapy; T helper cells; immune tolerance; IgE; IgG; T cells; B cells; mast cells; basophils; eosinophils	REGULATORY T-CELLS; IMMUNOLOGY/PRACTALL CONSENSUS REPORT; EOSINOPHIL CATIONIC PROTEIN; GRASS-POLLEN IMMUNOTHERAPY; TRANSCRIPTION FACTOR FOXP3; TOLL-LIKE RECEPTORS; HOUSE-DUST MITES; SUBLINGUAL IMMUNOTHERAPY; TGF-BETA; ASTHMATIC-CHILDREN	Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a desensitizing therapy for IgE-mediated allergic diseases and represents a potentially curative way of treatment. The mechanisms of action of AIT include the induction of very early desensitization of mast cells and basophils; generation of regulatory T and regulatory B (Breg) cell responses; regulation of IgE and IgG(4); decreases in numbers and activity of eosinophils and mast cells in mucosal allergic tissues; and decreases in the activity of basophils in circulation. Skewing of allergen-specific effector T and effector B cells to a regulatory phenotype appears as a key event in the course of AIT and normal immune response to allergens. Recently, inducible IL-10-secreting Breg cells were also demonstrated to contribute to allergen tolerance through suppression of effector T cells and selective induction of IgG4 isotype antibodies. Allergen-specific regulatory T and Breg cells orchestrate a general immunoregulatory activity, which can be summarized as suppression of cytokines from inflammatory dendritic cells; suppression of effector T(H)1, T(H)2, and T(H)17 cells; suppression of allergen-specific IgE and induction of IgG(4); and suppression of migration of mast cells, basophils, eosinophils, and effector T cells to tissues. A detailed knowledge of the mechanisms of AIT is not only important in designing the prevention and treatment of allergic diseases but might also find applications in the treatment of autoimmune diseases, organ transplantation, chronic infection, and cancer.	110	143	2014	11	10.1016/j.jaci.2013.12.1088	Allergy; Immunology
Pulmonary innate lymphoid cells are major producers of IL-5 and IL-13 in murine models of allergic asthma. Allergic asthma is characterized by chronic airway inflammation and hyperreactivity and is thought to be mediated by an adaptive T helper-2 (Th2) cell-type immune response. Here, we demonstrate that type 2 pulmonary innate lymphoid cells (ILC2s) significantly contribute to production of the key cytokines IL-5 and IL-13 in experimental asthma. In naive mice, lineage-marker negative ILC2s expressing IL-7Ra, CD25, Sca-1, and T1/ST2(IL-33R) were present in lungs and mediastinal lymph nodes (MedLNs), but not in broncho-alveolar lavage (BAL) fluid. Upon intranasal administration of IL-25 or IL-33, an asthma phenotype was induced, whereby ILC2s accumulated in lungs, MedLNs, and BAL fluid. After IL-25 and IL-33 administration, ILC2s constituted similar to 50 and similar to 80% of IL-5+/IL-13+ cells in lung and BAL, respectively. Also in house dust mite-induced or ovalbumin-induced allergic asthma, the ILC2 population in lung and BAL fluid increased significantly in size and ILC2s were a major source of IL-5 or IL-13. Particularly in OVA-induced asthma, the contribution of ILC2s to the total population of intracellular IL-5+ and IL-13+ cells in the lung was in the same range as found for Th2 cells. We conclude that both ILC2s and Th2 cells produce large amounts of IL-5 and IL-13 that contribute to allergic airway inflammation.. asthma| cytokines| house dust mite| innate immunity| innate lymphoid cells|ror-gamma-t| airway hyperreactivity| adaptive immunity| in-vivo| dendritic cells| type-2 immunity| nkp46(+) cells| lung| inflammation| cytokine.	MAY-2012	asthma| cytokines| house dust mite| innate immunity| innate lymphoid cells|ror-gamma-t| airway hyperreactivity| adaptive immunity| in-vivo| dendritic cells| type-2 immunity| nkp46(+) cells| lung| inflammation| cytokine	Wolterink, RGJK; KleinJan, A; van Nimwegen, M; Bergen, I; de Bruijn, M; Levani, Y; Hendriks, RW	Pulmonary innate lymphoid cells are major producers of IL-5 and IL-13 in murine models of allergic asthma		EUROPEAN JOURNAL OF IMMUNOLOGY	Asthma; Cytokines; House dust mite; Innate immunity; Innate lymphoid cells	ROR-GAMMA-T; AIRWAY HYPERREACTIVITY; ADAPTIVE IMMUNITY; IN-VIVO; DENDRITIC CELLS; TYPE-2 IMMUNITY; NKP46(+) CELLS; LUNG; INFLAMMATION; CYTOKINE	Allergic asthma is characterized by chronic airway inflammation and hyperreactivity and is thought to be mediated by an adaptive T helper-2 (Th2) cell-type immune response. Here, we demonstrate that type 2 pulmonary innate lymphoid cells (ILC2s) significantly contribute to production of the key cytokines IL-5 and IL-13 in experimental asthma. In naive mice, lineage-marker negative ILC2s expressing IL-7Ra, CD25, Sca-1, and T1/ST2(IL-33R) were present in lungs and mediastinal lymph nodes (MedLNs), but not in broncho-alveolar lavage (BAL) fluid. Upon intranasal administration of IL-25 or IL-33, an asthma phenotype was induced, whereby ILC2s accumulated in lungs, MedLNs, and BAL fluid. After IL-25 and IL-33 administration, ILC2s constituted similar to 50 and similar to 80% of IL-5+/IL-13+ cells in lung and BAL, respectively. Also in house dust mite-induced or ovalbumin-induced allergic asthma, the ILC2 population in lung and BAL fluid increased significantly in size and ILC2s were a major source of IL-5 or IL-13. Particularly in OVA-induced asthma, the contribution of ILC2s to the total population of intracellular IL-5+ and IL-13+ cells in the lung was in the same range as found for Th2 cells. We conclude that both ILC2s and Th2 cells produce large amounts of IL-5 and IL-13 that contribute to allergic airway inflammation.	43	143	2012	11	10.1002/eji.201142018	Immunology
The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose. Background: In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives: We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods: Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results: Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (chi(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001). Conclusion: The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy. (J Allergy Clin Immunol 2011;127:1286-93.). ticks| anaphylaxis| oligosaccharide| alpha-gal| ige antibody to ccd|amblyomma-americanum acari| united-states| colorectal-cancer| indoor allergen| acute asthma| cetuximab| anaphylaxis| humans| risk| sensitization.	MAY-2011	ticks| anaphylaxis| oligosaccharide| alpha-gal| ige antibody to ccd|amblyomma-americanum acari| united-states| colorectal-cancer| indoor allergen| acute asthma| cetuximab| anaphylaxis| humans| risk| sensitization	Commins, SP; James, HR; Kelly, LA; Pochan, SL; Workman, LJ; Perzanowski, MS; Kocan, KM; Fahy, JV; Nganga, LW; Ronmark, E; Cooper, PJ; Platts-Mills, TAE	The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Ticks; anaphylaxis; oligosaccharide; alpha-gal; IgE antibody to CCD	AMBLYOMMA-AMERICANUM ACARI; UNITED-STATES; COLORECTAL-CANCER; INDOOR ALLERGEN; ACUTE ASTHMA; CETUXIMAB; ANAPHYLAXIS; HUMANS; RISK; SENSITIZATION	Background: In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives: We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Methods: Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Results: Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (chi(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001). Conclusion: The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy. (J Allergy Clin Immunol 2011;127:1286-93.)	42	143	2011	14	10.1016/j.jaci.2011.02.019	Allergy; Immunology
COPD in Never Smokers Results From the Population-Based Burden of Obstructive Lung Disease Study. Background: Never smokers comprise a substantial proportion of patients with COPD. Their characteristics and possible risk factors in this population are not yet well defined. Methods: We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study. Participants were aged >= 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines. In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio. Results: Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD. Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD. This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio. Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations. Conclusion: This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD. Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. CHEST 2011; 139(4):752-763. nutrition examination survey| environmental tobacco-smoke| air-flow obstruction| 3rd national-health| pulmonary-disease| grain dust| gender-differences| passive smoking| biomass smoke| us population.	APR-2011	nutrition examination survey| environmental tobacco-smoke| air-flow obstruction| 3rd national-health| pulmonary-disease| grain dust| gender-differences| passive smoking| biomass smoke| us population	Lamprecht, B; McBurnie, MA; Vollmer, WM; Gudmundsson, G; Welte, T; Nizankowska-Mogilnicka, E; Studnicka, M; Bateman, E; Anto, JM; Burney, P; Mannino, DM; Buist, SA	COPD in Never Smokers Results From the Population-Based Burden of Obstructive Lung Disease Study		CHEST		NUTRITION EXAMINATION SURVEY; ENVIRONMENTAL TOBACCO-SMOKE; AIR-FLOW OBSTRUCTION; 3RD NATIONAL-HEALTH; PULMONARY-DISEASE; GRAIN DUST; GENDER-DIFFERENCES; PASSIVE SMOKING; BIOMASS SMOKE; US POPULATION	Background: Never smokers comprise a substantial proportion of patients with COPD. Their characteristics and possible risk factors in this population are not yet well defined. Methods: We analyzed data from 14 countries that participated in the international, population-based Burden of Obstructive Lung Disease (BOLD) study. Participants were aged >= 40 years and completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. A diagnosis of COPD was based on the postbronchodilator FEV1/FVC ratio, according to current GOLD (Global Initiative for Obstructive Lung Disease) guidelines. In addition to this, the lower limit of normal (LLN) was evaluated as an alternative threshold for the FEV1/FVC ratio. Results: Among 4,291 never smokers, 6.6% met criteria for mild (GOLD stage I) COPD, and 5.6% met criteria for moderate to very severe (GOLD stage II+) COPD. Although never smokers were less likely to have COPD and had less severe COPD than ever smokers, never smokers nonetheless comprised 23.3% (240/1,031) of those classified with GOLD stage II+ COPD. This proportion was similar, 20.5% (171/832), even when the LLN was used as a threshold for the FEV1/FVC ratio. Predictors of COPD in never smokers include age, education, occupational exposure, childhood respiratory diseases, and BMI alterations. Conclusion: This multicenter international study confirms previous evidence that never smokers comprise a substantial proportion of individuals with COPD. Our data suggest that, in addition to increased age, a prior diagnosis of asthma and, among women, lower education levels are associated with an increased risk for COPD among never smokers. CHEST 2011; 139(4):752-763	49	143	2011	12	10.1378/chest.10-1253	General & Internal Medicine; Respiratory System
Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy. Genome scans for asthma have identified suggestive or significant linkages on 17 different chromosomes, including chromosome 12, region q13-23, housing the vitamin D receptor (VDR) gene. Through interaction with VDR, 1,25-dihydroxyvitamin D3 mediates numerous biological activities, such as regulation of helper T-cell development and subsequent cytokine secretion profiles. Variants of the VDR have been found to be associated with immune-mediated diseases that are characterized by an imbalance in helper T-cell development, such as Crohn's disease and tuberculosis. The VDR, hence, is a good candidate to be investigated for association with asthma, which is characterized by enhanced helper T-cell type 2 activity. Here, we examined VDR genetic variants in an asthma family-based cohort from Quebec. We report six variants to be strongly associated with asthma and four with atopy (0.0005 less than or equal to p less than or equal to 0.05). Analysis of the linkage disequilibrium pattern and haplotypes also revealed significant association with both phenotypes (0.0004 less than or equal to p less than or equal to 0.01). The findings have been replicated by another research team in a second but not in a third cohort. These results identify VDR variants as genetic risk factors for asthma/atopy and implicate a non-human leukocyte antigen immunoregulatory molecule in the pathogenesis of asthma and atopy.. genetic predisposition| polymorphism| vitamin d receptor|family-based tests| 1,25-dihydroxyvitamin d-3| chemokine receptor| onset asthma| bone-density| polymorphism| tuberculosis| alleles| disease| progression.	NOV 1-2004	genetic predisposition| polymorphism| vitamin d receptor|family-based tests| 1,25-dihydroxyvitamin d-3| chemokine receptor| onset asthma| bone-density| polymorphism| tuberculosis| alleles| disease| progression	Poon, AH; Laprise, C; Lemire, M; Montpetit, A; Sinnett, D; Schurr, E; Hudson, TJ	Association of vitamin D receptor genetic variants with susceptibility to asthma and atopy		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	genetic predisposition; polymorphism; vitamin D receptor	FAMILY-BASED TESTS; 1,25-DIHYDROXYVITAMIN D-3; CHEMOKINE RECEPTOR; ONSET ASTHMA; BONE-DENSITY; POLYMORPHISM; TUBERCULOSIS; ALLELES; DISEASE; PROGRESSION	Genome scans for asthma have identified suggestive or significant linkages on 17 different chromosomes, including chromosome 12, region q13-23, housing the vitamin D receptor (VDR) gene. Through interaction with VDR, 1,25-dihydroxyvitamin D3 mediates numerous biological activities, such as regulation of helper T-cell development and subsequent cytokine secretion profiles. Variants of the VDR have been found to be associated with immune-mediated diseases that are characterized by an imbalance in helper T-cell development, such as Crohn's disease and tuberculosis. The VDR, hence, is a good candidate to be investigated for association with asthma, which is characterized by enhanced helper T-cell type 2 activity. Here, we examined VDR genetic variants in an asthma family-based cohort from Quebec. We report six variants to be strongly associated with asthma and four with atopy (0.0005 less than or equal to p less than or equal to 0.05). Analysis of the linkage disequilibrium pattern and haplotypes also revealed significant association with both phenotypes (0.0004 less than or equal to p less than or equal to 0.01). The findings have been replicated by another research team in a second but not in a third cohort. These results identify VDR variants as genetic risk factors for asthma/atopy and implicate a non-human leukocyte antigen immunoregulatory molecule in the pathogenesis of asthma and atopy.	57	143	2004	7	10.1164/rccm.200403-412oc	General & Internal Medicine; Respiratory System
Effect of weight reduction on respiratory function and airway reactivity in obese women. Background: Population-based studies have documented an association between obesity and an increased prevalence of asthma in women. Methods: We prospectively studied 58 obese women with a body mass index of > 30 kg/m(2), 24 of whom had asthma, who were enrolled in an intensive 6-month weight loss program to determine whether loss of body mass would be correlated with improvements in bronchial reactivity, lung function, and disease-specific health status. Results: Patients lost air average of 20 kg over the 6-month period. For every 10% relative loss of weight, the FVC improved by 92 mL (p = 0.05) and the FEV1 improved by 73 mL (p = 0.04), however, bronchial reactivity did not significantly change with weight loss (p = 0.23). Patients who lost > 13% of their pretreatment weight experienced improvements in FEV1 (p = 0.01), FVC (p = 0.02), and total lung capacity (p = 0.05) compared to patients in the lowest quartile who failed to lose significant amounts of weight. Neither group experienced any significant change in methacholine responsiveness (p = 0.57). Patients who completed the 6-month weight loss program experienced improvements in respiratory health status, irrespective of weight loss. Conclusion: We concluded that weight loss can improve lung function in obese women, however, the improvements appear to be independent of changes in airway reactivity.. asthma| obesity| pulmonary function|asthma| health.	JUN-2004	asthma| obesity| pulmonary function|asthma| health	Aaron, SD; Fergusson, D; Dent, R; Chen, Y; Vandemheen, KL; Dales, RE	Effect of weight reduction on respiratory function and airway reactivity in obese women		CHEST	asthma; obesity; pulmonary function	ASTHMA; HEALTH	Background: Population-based studies have documented an association between obesity and an increased prevalence of asthma in women. Methods: We prospectively studied 58 obese women with a body mass index of > 30 kg/m(2), 24 of whom had asthma, who were enrolled in an intensive 6-month weight loss program to determine whether loss of body mass would be correlated with improvements in bronchial reactivity, lung function, and disease-specific health status. Results: Patients lost air average of 20 kg over the 6-month period. For every 10% relative loss of weight, the FVC improved by 92 mL (p = 0.05) and the FEV1 improved by 73 mL (p = 0.04), however, bronchial reactivity did not significantly change with weight loss (p = 0.23). Patients who lost > 13% of their pretreatment weight experienced improvements in FEV1 (p = 0.01), FVC (p = 0.02), and total lung capacity (p = 0.05) compared to patients in the lowest quartile who failed to lose significant amounts of weight. Neither group experienced any significant change in methacholine responsiveness (p = 0.57). Patients who completed the 6-month weight loss program experienced improvements in respiratory health status, irrespective of weight loss. Conclusion: We concluded that weight loss can improve lung function in obese women, however, the improvements appear to be independent of changes in airway reactivity.	17	143	2004	7	10.1378/chest.125.6.2046	General & Internal Medicine; Respiratory System
Anxiety and depression are related to the outcome of emergency treatment in patients with obstructive pulmonary disease. Study objectives: To investigate whether psychological factors predict outcome after emergency treatment for obstructive pulmonary disease. Setting: Emergency department at a university hospital. Patients: Forty-three patients presenting with exacerbation of asthma or COPD. Intervention: The patients received emergency treatment and were followed up for 4 weeks. Measurement: Spirometry, blood sampling, pulse oximetry, breathing rate, pulse rate, and dyspnea score was measured before and during emergency treatment. The psychological status was assessed using the hospital anxiety and depression (HAD) scale questionnaire at the end of the follow-up period. Results: Anxiety and/or depression was found in 17 patients (40%). Of these patients, nine patients (53%) were admitted to hospital or had a relapse within 1 month, compared with five patients (19%) in the group without anxiety and/or depression (p < 0.05). Among patients who relapsed within 1 month (n = 14), the HAD total score was 12.4 +/- 5.9 compared with 8.6 +/- 5.1 (mean +/- SD) among the patients without a relapse (p < 0.05). After making adjustments for age, gender, atopic status, treatment, and pack-years, the significant association between treatment failure and anxiety and/or depression still remained. Conclusion: Our study indicates that anxiety and depression are related to the outcome of emergency treatment in patients with obstructive pulmonary disease. Further studies should be conducted evaluating the effect of treatment of anxiety and depression in patients with recurrent exacerbations of asthma and COPD.. anxiety| asthma| copd| depression| emergency treatment| relapse|air-flow obstruction| near-fatal asthma| hospital anxiety| risk-factors| lung-disease| scale| morbidity| symptoms| life| breathlessness.	NOV-2002	anxiety| asthma| copd| depression| emergency treatment| relapse|air-flow obstruction| near-fatal asthma| hospital anxiety| risk-factors| lung-disease| scale| morbidity| symptoms| life| breathlessness	Dahlen, I; Janson, C	Anxiety and depression are related to the outcome of emergency treatment in patients with obstructive pulmonary disease		CHEST	anxiety; asthma; COPD; depression; emergency treatment; relapse	AIR-FLOW OBSTRUCTION; NEAR-FATAL ASTHMA; HOSPITAL ANXIETY; RISK-FACTORS; LUNG-DISEASE; SCALE; MORBIDITY; SYMPTOMS; LIFE; BREATHLESSNESS	Study objectives: To investigate whether psychological factors predict outcome after emergency treatment for obstructive pulmonary disease. Setting: Emergency department at a university hospital. Patients: Forty-three patients presenting with exacerbation of asthma or COPD. Intervention: The patients received emergency treatment and were followed up for 4 weeks. Measurement: Spirometry, blood sampling, pulse oximetry, breathing rate, pulse rate, and dyspnea score was measured before and during emergency treatment. The psychological status was assessed using the hospital anxiety and depression (HAD) scale questionnaire at the end of the follow-up period. Results: Anxiety and/or depression was found in 17 patients (40%). Of these patients, nine patients (53%) were admitted to hospital or had a relapse within 1 month, compared with five patients (19%) in the group without anxiety and/or depression (p < 0.05). Among patients who relapsed within 1 month (n = 14), the HAD total score was 12.4 +/- 5.9 compared with 8.6 +/- 5.1 (mean +/- SD) among the patients without a relapse (p < 0.05). After making adjustments for age, gender, atopic status, treatment, and pack-years, the significant association between treatment failure and anxiety and/or depression still remained. Conclusion: Our study indicates that anxiety and depression are related to the outcome of emergency treatment in patients with obstructive pulmonary disease. Further studies should be conducted evaluating the effect of treatment of anxiety and depression in patients with recurrent exacerbations of asthma and COPD.	39	143	2002	5	10.1378/chest.122.5.1633	General & Internal Medicine; Respiratory System
Cooperative effects of Th2 cytokines and allergen on normal and asthmatic bronchial epithelial cells. In sensitized individuals, exposure to allergens such as Dermatophagoides pteronyssinus (Der p) causes Th2 polarization and release of cytokines, including IL-4 and IL-13. Because Der p extracts also have direct effects on epithelial cells, we hypothesized that allergen augments the effects of Th2 cytokines by promoting mediator release from the bronchial epithelium in allergic asthma. To test our hypothesis, primary bronchial epithelial cultures were grown from bronchial brushings of normal and atopic asthmatic subjects. RT-PCR showed that each culture expressed IL-4Ralpha, common gamma-chain, and IL-13Ralpha(1), as well as IL-13Ralpha(2), which negatively regulates IL-13 signaling; FACS analysis confirmed IL-13Ralpha(2) protein expression. Exposure of epithelial cultures to either Der p extracts, TNF-alpha, IL-4, or IL-13 enhanced GM-CSF and IL-8 release, and this was partially suppressible by corticosteroids. Simultaneous exposure of the epithelial cultures to IL-4 or IL-13 together with Der p resulted in a further increase in cytokine release, which was at least additive. Release of TGF-alpha was also increased by TNF-a and combinations of IL-4, IL-13, and Der p; however, this stimulation was only significant in the asthma-derived cultures. These data suggest that, in an allergic environment, Th2 cytokines and allergen have the potential to sustain airway inflammation through a cooperative effect on cytokine release by the bronchial epithelium. Our novel finding that IL-4, IL-13, and allergen enhance release of TGF-a, a ligand for the epidermal growth factor receptor that stimulates fibroblast proliferation and goblet cell differentiation, provides a potential link between allergen exposure, Th2 cytokines, and airway remodelling in asthma.. diesel exhaust particles| in-vitro| inflammatory cytokine| nonasthmatic subjects| genetic-variants| ile50val variant| il-4 receptor| socs proteins| ige synthesis| expression.	JUL 1-2002	diesel exhaust particles| in-vitro| inflammatory cytokine| nonasthmatic subjects| genetic-variants| ile50val variant| il-4 receptor| socs proteins| ige synthesis| expression	Lordan, JL; Bucchieri, F; Richter, A; Konstantinidis, A; Holloway, JW; Thornber, M; Puddicombe, SM; Buchanan, D; Wilson, SJ; Djukanovic, R; Holgate, ST; Davies, DE	Cooperative effects of Th2 cytokines and allergen on normal and asthmatic bronchial epithelial cells		JOURNAL OF IMMUNOLOGY		DIESEL EXHAUST PARTICLES; IN-VITRO; INFLAMMATORY CYTOKINE; NONASTHMATIC SUBJECTS; GENETIC-VARIANTS; ILE50VAL VARIANT; IL-4 RECEPTOR; SOCS PROTEINS; IGE SYNTHESIS; EXPRESSION	In sensitized individuals, exposure to allergens such as Dermatophagoides pteronyssinus (Der p) causes Th2 polarization and release of cytokines, including IL-4 and IL-13. Because Der p extracts also have direct effects on epithelial cells, we hypothesized that allergen augments the effects of Th2 cytokines by promoting mediator release from the bronchial epithelium in allergic asthma. To test our hypothesis, primary bronchial epithelial cultures were grown from bronchial brushings of normal and atopic asthmatic subjects. RT-PCR showed that each culture expressed IL-4Ralpha, common gamma-chain, and IL-13Ralpha(1), as well as IL-13Ralpha(2), which negatively regulates IL-13 signaling; FACS analysis confirmed IL-13Ralpha(2) protein expression. Exposure of epithelial cultures to either Der p extracts, TNF-alpha, IL-4, or IL-13 enhanced GM-CSF and IL-8 release, and this was partially suppressible by corticosteroids. Simultaneous exposure of the epithelial cultures to IL-4 or IL-13 together with Der p resulted in a further increase in cytokine release, which was at least additive. Release of TGF-alpha was also increased by TNF-a and combinations of IL-4, IL-13, and Der p; however, this stimulation was only significant in the asthma-derived cultures. These data suggest that, in an allergic environment, Th2 cytokines and allergen have the potential to sustain airway inflammation through a cooperative effect on cytokine release by the bronchial epithelium. Our novel finding that IL-4, IL-13, and allergen enhance release of TGF-a, a ligand for the epidermal growth factor receptor that stimulates fibroblast proliferation and goblet cell differentiation, provides a potential link between allergen exposure, Th2 cytokines, and airway remodelling in asthma.	50	143	2002	8		Immunology
High constitutive glucocorticoid receptor beta in human neutrophils enables them to reduce their spontaneous rate of cell death in response to corticosteroids. Neutrophils are markedly less sensitive to glucocorticoids than T cells, making it difficult to control inflammation in neutrophil-mediated diseases. Development of new antiinflammatory strategies for such diseases would be aided by an understanding of mechanisms underlying differential steroid responsiveness. Two protein isoforms of the human glucocorticoid receptor (GR) exist, GR alpha and GR beta, which arise from alternative splicing of the GR pre-mRNA primary transcripts. GR beta does not bind glucocorticoids and is an inhibitor of GR alpha activity. Relative amounts of these two GRs can therefore determine the level of glucocorticoid sensitivity. In this study, human neutrophils and peripheral blood mononuclear cells (PBMCs) were studied to determine the relative amounts of each GR isoform. The mean fluorescence intensity (MFI) using immunofluorescence analysis for GR alpha was 475 +/- 62 and 985 +/- 107 for PBMCs and neutrophils, respectively. For GR beta, the MFI was 350 +/- 60 and 1,389 +/- 143 for PBMCs and neutrophils, respectively (P < 0.05). After interleukin (IL)-8 stimulation of neutrophils, there was a statistically significant increase in intensity of GR<beta> staining to 2,497 +/- 140 (P < 0.05). No change in GR<alpha> expression was observed. This inversion of the GR alpha /GR beta ratio in human neutrophils compared with PBMCs was confirmed by quantitative Western analysis. Increased GR beta mRNA expression in neutrophils at baseline, and after IL-8 exposure, was observed using RNA dot blot analysis. Increased levels of GR alpha /GR beta heterodimers were found in neutrophils as compared with PBMCs using coimmunoprecipitation/Western analysis. Transfection of mouse neutrophils, which do not contain GR beta, resulted in a significant reduction in the rate of cell death when treated with dexamethasone. We conclude that high constitutive expression of GR beta by human neutrophils may provide a mechanism by which these cells escape glucocorticoid-induced cell death. Moreover, upregulation of this GR by proinflammatory cytokines such as IL-8 further enhances their survival in the presence of glucocorticoids during inflammation.. neutrophils| glucocorticoid insensitivity| glucocorticoid receptor| interleukin 8| inflammation|streptolysin-o| apoptosis| isoform| expression| binding| dexamethasone| inflammation| specificity| asthma.	MAR 5-2001	neutrophils| glucocorticoid insensitivity| glucocorticoid receptor| interleukin 8| inflammation|streptolysin-o| apoptosis| isoform| expression| binding| dexamethasone| inflammation| specificity| asthma	Strickland, I; Kisich, K; Hauk, PJ; Vottero, A; Chrousos, GP; Klemm, DJ; Leung, DYM	High constitutive glucocorticoid receptor beta in human neutrophils enables them to reduce their spontaneous rate of cell death in response to corticosteroids		JOURNAL OF EXPERIMENTAL MEDICINE	neutrophils; glucocorticoid insensitivity; glucocorticoid receptor; interleukin 8; inflammation	STREPTOLYSIN-O; APOPTOSIS; ISOFORM; EXPRESSION; BINDING; DEXAMETHASONE; INFLAMMATION; SPECIFICITY; ASTHMA	Neutrophils are markedly less sensitive to glucocorticoids than T cells, making it difficult to control inflammation in neutrophil-mediated diseases. Development of new antiinflammatory strategies for such diseases would be aided by an understanding of mechanisms underlying differential steroid responsiveness. Two protein isoforms of the human glucocorticoid receptor (GR) exist, GR alpha and GR beta, which arise from alternative splicing of the GR pre-mRNA primary transcripts. GR beta does not bind glucocorticoids and is an inhibitor of GR alpha activity. Relative amounts of these two GRs can therefore determine the level of glucocorticoid sensitivity. In this study, human neutrophils and peripheral blood mononuclear cells (PBMCs) were studied to determine the relative amounts of each GR isoform. The mean fluorescence intensity (MFI) using immunofluorescence analysis for GR alpha was 475 +/- 62 and 985 +/- 107 for PBMCs and neutrophils, respectively. For GR beta, the MFI was 350 +/- 60 and 1,389 +/- 143 for PBMCs and neutrophils, respectively (P < 0.05). After interleukin (IL)-8 stimulation of neutrophils, there was a statistically significant increase in intensity of GR<beta> staining to 2,497 +/- 140 (P < 0.05). No change in GR<alpha> expression was observed. This inversion of the GR alpha /GR beta ratio in human neutrophils compared with PBMCs was confirmed by quantitative Western analysis. Increased GR beta mRNA expression in neutrophils at baseline, and after IL-8 exposure, was observed using RNA dot blot analysis. Increased levels of GR alpha /GR beta heterodimers were found in neutrophils as compared with PBMCs using coimmunoprecipitation/Western analysis. Transfection of mouse neutrophils, which do not contain GR beta, resulted in a significant reduction in the rate of cell death when treated with dexamethasone. We conclude that high constitutive expression of GR beta by human neutrophils may provide a mechanism by which these cells escape glucocorticoid-induced cell death. Moreover, upregulation of this GR by proinflammatory cytokines such as IL-8 further enhances their survival in the presence of glucocorticoids during inflammation.	29	143	2001	9	10.1084/jem.193.5.585	Immunology; Research & Experimental Medicine
Role of endothelin-1 in lung disease. Endothelin-1 (ET-1) is a 21 amino acid peptide with diverse biological activity that has been implicated in numerous diseases. ET-1 is a potent mitogen regulator of smooth muscle tone, and inflammatory mediator that may play a key role in diseases of the airways, pulmonary circulation, and inflammatory lung diseases, both acute and chronic. This review will focus on the biology of ET-1 and its role in lung disease.. asthma| endothelin| fibrosis| inflammation| pulmonary hypertension|bronchoalveolar lavage fluid| obstructive pulmonary-disease| respiratory-distress-syndrome| bronchial epithelial-cells| perfused rat lungs| collagen gel contraction| guinea-pig pulmonary| air-flow obstruction| smooth-muscle cells| plasma endothelin-1.	2001	asthma| endothelin| fibrosis| inflammation| pulmonary hypertension|bronchoalveolar lavage fluid| obstructive pulmonary-disease| respiratory-distress-syndrome| bronchial epithelial-cells| perfused rat lungs| collagen gel contraction| guinea-pig pulmonary| air-flow obstruction| smooth-muscle cells| plasma endothelin-1	Fagan, KA; McMurtry, IF; Rodman, DM	Role of endothelin-1 in lung disease		RESPIRATORY RESEARCH	asthma; endothelin; fibrosis; inflammation; pulmonary hypertension	BRONCHOALVEOLAR LAVAGE FLUID; OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY-DISTRESS-SYNDROME; BRONCHIAL EPITHELIAL-CELLS; PERFUSED RAT LUNGS; COLLAGEN GEL CONTRACTION; GUINEA-PIG PULMONARY; AIR-FLOW OBSTRUCTION; SMOOTH-MUSCLE CELLS; PLASMA ENDOTHELIN-1	Endothelin-1 (ET-1) is a 21 amino acid peptide with diverse biological activity that has been implicated in numerous diseases. ET-1 is a potent mitogen regulator of smooth muscle tone, and inflammatory mediator that may play a key role in diseases of the airways, pulmonary circulation, and inflammatory lung diseases, both acute and chronic. This review will focus on the biology of ET-1 and its role in lung disease.	174	143	2001	12	10.1186/rr44	Respiratory System
Nomenclature and structural biology of allergens. Purified allergens are named using the systematic nomenclature of the Allergen Nomenclature Sub-Committee of the World Health Organization and International Union of Immunological Societies. The system uses abbreviated Linnean genus and species names and an Arabic number to indicate the chronology of allergen purification. Most major allergens from mites, animal dander, pollens, insects, and foods have been cloned, and more than 40 three-dimensional allergen structures are in the Protein Database. Allergens are derived from proteins with a variety of biologic functions, including proteases, ligand-binding proteins, structural proteins, pathogenesis-related proteins, lipid transfer proteins, profilins, and calcium-binding proteins. Biologic function, such as the proteolytic enzyme allergens of dust mites, might directly influence the development of IgE responses and might initiate inflammatory responses in the lung that are associated with asthma. Intrinsic structural or biologic properties might also influence the extent to which allergens persist in indoor and outdoor environments or retain their allergenicity in the digestive tract. Analyses of the protein family database suggest that the universe of allergens comprises more than 120 distinct protein families. Structural biology and proteomics define recombinant allergen targets for diagnostic and therapeutic purposes and identify motifs, patterns, and structures of immunologic significance.. allergen| nomenclature| ige| asthma| protein families| allergic disease| protein structure| biologic function|birch pollen allergen| dust-mite allergens| seed storage proteins| plant food allergens| crystal-structure| cross-reactivity| cat allergen| binding| cockroach| immunotherapy.	FEB-2007	allergen| nomenclature| ige| asthma| protein families| allergic disease| protein structure| biologic function|birch pollen allergen| dust-mite allergens| seed storage proteins| plant food allergens| crystal-structure| cross-reactivity| cat allergen| binding| cockroach| immunotherapy	Chapman, MD; Pomes, A; Breiteneder, H; Ferreira, F	Nomenclature and structural biology of allergens		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen; nomenclature; IgE; asthma; protein families; allergic disease; protein structure; biologic function	BIRCH POLLEN ALLERGEN; DUST-MITE ALLERGENS; SEED STORAGE PROTEINS; PLANT FOOD ALLERGENS; CRYSTAL-STRUCTURE; CROSS-REACTIVITY; CAT ALLERGEN; BINDING; COCKROACH; IMMUNOTHERAPY	Purified allergens are named using the systematic nomenclature of the Allergen Nomenclature Sub-Committee of the World Health Organization and International Union of Immunological Societies. The system uses abbreviated Linnean genus and species names and an Arabic number to indicate the chronology of allergen purification. Most major allergens from mites, animal dander, pollens, insects, and foods have been cloned, and more than 40 three-dimensional allergen structures are in the Protein Database. Allergens are derived from proteins with a variety of biologic functions, including proteases, ligand-binding proteins, structural proteins, pathogenesis-related proteins, lipid transfer proteins, profilins, and calcium-binding proteins. Biologic function, such as the proteolytic enzyme allergens of dust mites, might directly influence the development of IgE responses and might initiate inflammatory responses in the lung that are associated with asthma. Intrinsic structural or biologic properties might also influence the extent to which allergens persist in indoor and outdoor environments or retain their allergenicity in the digestive tract. Analyses of the protein family database suggest that the universe of allergens comprises more than 120 distinct protein families. Structural biology and proteomics define recombinant allergen targets for diagnostic and therapeutic purposes and identify motifs, patterns, and structures of immunologic significance.	44	142	2007	7	10.1016/j.jaci.2006.11.001	Allergy; Immunology
The relationship of urban design to human health and condition. The population of the United States of America is currently experiencing increased illness from dispersed and synergistic causes. Many of the acute insults of the past have receded due to centralized health care and regulatory action. However, chronic ailments including asthma and allergies, animal-transmitted diseases, obesity, diabetes, heart disease, and depression are on the rise. These diverse illnesses join with forest fragmentation, stream degradation, wetlands destruction, and the concomitant loss of native species to suggest detrimental contributions from the built environment. This paper surveys the state of the science on the impacts of urban design on human health and well-being. Drawing primarily on recent peer-reviewed literature in a broad array of health, planning, and environmental fields, it outlines the influence of design at three spatial scales on aspects of physical and mental health, and social and cultural vibrancy. Selected ecological effects are also discussed to illustrate shared associations with urbanization. While causal chains are generally complex and not always completely understood, sufficient evidence exists to reveal urban design as a powerful tool for improving human condition. Solutions are discussed at the personal and professional level, emphasizing cross-disciplinary collaboration in urban planning and design, and the participation of residents in shaping their living environment. At the parcel scale, greenery and access to it visually and physically are the principal keys to health. These elements must be incorporated into relatively high-density neighborhood designs that include public buildings, open space, mixed land use, and pedestrian walkways to increase physical exercise and enhance civic life. Finally, neighborhoods must be embedded in existing urban infrastructure to provide larger cultural and business opportunities and reduce reliance on the automobile. Further research is recommended to strengthen the associations between design and health. Increased communication on this subject is also necessary between design and health practitioners and their clients and colleagues. (C) 2002 Elsevier Science B.V. All rights reserved.. ecological design| public health| social capital|lyme-disease| risk| environment| community| people| home.	AUG 15-2003	ecological design| public health| social capital|lyme-disease| risk| environment| community| people| home	Jackson, LE	The relationship of urban design to human health and condition		LANDSCAPE AND URBAN PLANNING	ecological design; public health; social capital	LYME-DISEASE; RISK; ENVIRONMENT; COMMUNITY; PEOPLE; HOME	The population of the United States of America is currently experiencing increased illness from dispersed and synergistic causes. Many of the acute insults of the past have receded due to centralized health care and regulatory action. However, chronic ailments including asthma and allergies, animal-transmitted diseases, obesity, diabetes, heart disease, and depression are on the rise. These diverse illnesses join with forest fragmentation, stream degradation, wetlands destruction, and the concomitant loss of native species to suggest detrimental contributions from the built environment. This paper surveys the state of the science on the impacts of urban design on human health and well-being. Drawing primarily on recent peer-reviewed literature in a broad array of health, planning, and environmental fields, it outlines the influence of design at three spatial scales on aspects of physical and mental health, and social and cultural vibrancy. Selected ecological effects are also discussed to illustrate shared associations with urbanization. While causal chains are generally complex and not always completely understood, sufficient evidence exists to reveal urban design as a powerful tool for improving human condition. Solutions are discussed at the personal and professional level, emphasizing cross-disciplinary collaboration in urban planning and design, and the participation of residents in shaping their living environment. At the parcel scale, greenery and access to it visually and physically are the principal keys to health. These elements must be incorporated into relatively high-density neighborhood designs that include public buildings, open space, mixed land use, and pedestrian walkways to increase physical exercise and enhance civic life. Finally, neighborhoods must be embedded in existing urban infrastructure to provide larger cultural and business opportunities and reduce reliance on the automobile. Further research is recommended to strengthen the associations between design and health. Increased communication on this subject is also necessary between design and health practitioners and their clients and colleagues. (C) 2002 Elsevier Science B.V. All rights reserved.	50	142	2003	10	10.1016/S0169-2046(02)00230-X	Environmental Sciences & Ecology; Geography; Physical Geography; Urban Studies
The importance of prenatal exposures on the development of allergic disease - A birth cohort study using the West Midlands General Practice Database. The etiology of allergic disease is not understood, but a decreased exposure to infection may play an important role. There are few published data on the impact of change in microbial exposure during pregnancy on the child's risk of developing allergic disease. Using a birth cohort of 24,690 children, derived from the West Midlands General Practice Research Database, we investigated a number of perinatal exposures on the incidence of asthma, eczema, and hay fever. Our findings suggest that exposure to antibiotics in utero is associated with an increased risk of asthma in a dose-related manner (more than two courses of antibiotics compared wit ne adjusted hazard ratio [HR] 1.68; 95% confidence interval [CI], 1.51-1.87), and similar associations are present for eczema (adjust HR 1.17; 95% CI, 1.06-1.29) and hay fever (adjusted HR 1.56; 95% CI, 1.22-2.01). Exposure to a range of infections in utero was also associated with a small increased risk of developing allergic disease. Strong protective effects of older siblings on the incidence of allergy are present within this cohort, but previous pregnancies that did not result in a live birth were not protective. Our findings suggest that exposure to antibiotics and to infections in utero is a potentially important risk factor in the development of allergic disease.. asthma| epidemiology| hay fever| eczema| perinatal exposures|cord blood| hay-fever| atopic disorders| asthmatic women| early-childhood| family-size| new-zealand| in-utero| risk| infections.	SEP 15-2002	asthma| epidemiology| hay fever| eczema| perinatal exposures|cord blood| hay-fever| atopic disorders| asthmatic women| early-childhood| family-size| new-zealand| in-utero| risk| infections	McKeever, TM; Lewis, SA; Smith, C; Hubbard, R	The importance of prenatal exposures on the development of allergic disease - A birth cohort study using the West Midlands General Practice Database		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; epidemiology; hay fever; eczema; perinatal exposures	CORD BLOOD; HAY-FEVER; ATOPIC DISORDERS; ASTHMATIC WOMEN; EARLY-CHILDHOOD; FAMILY-SIZE; NEW-ZEALAND; IN-UTERO; RISK; INFECTIONS	The etiology of allergic disease is not understood, but a decreased exposure to infection may play an important role. There are few published data on the impact of change in microbial exposure during pregnancy on the child's risk of developing allergic disease. Using a birth cohort of 24,690 children, derived from the West Midlands General Practice Research Database, we investigated a number of perinatal exposures on the incidence of asthma, eczema, and hay fever. Our findings suggest that exposure to antibiotics in utero is associated with an increased risk of asthma in a dose-related manner (more than two courses of antibiotics compared wit ne adjusted hazard ratio [HR] 1.68; 95% confidence interval [CI], 1.51-1.87), and similar associations are present for eczema (adjust HR 1.17; 95% CI, 1.06-1.29) and hay fever (adjusted HR 1.56; 95% CI, 1.22-2.01). Exposure to a range of infections in utero was also associated with a small increased risk of developing allergic disease. Strong protective effects of older siblings on the incidence of allergy are present within this cohort, but previous pregnancies that did not result in a live birth were not protective. Our findings suggest that exposure to antibiotics and to infections in utero is a potentially important risk factor in the development of allergic disease.	37	142	2002	6	10.1164/rccm.200202-158OC	General & Internal Medicine; Respiratory System
"An unexpected version of horror autotoxicus: anaphylactic shock to a self peptide. EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypicT helper I (THI) cell-mediated autoimmune disease, it can also be induced by T(H)2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is associated with exposure to a foreign antigen that is often derived from medication, insect venom or food. We report here that, after self-tolerance to myelin is destroyed, anaphylaxis may be triggered by a self-antigen, in this case a myelin peptide. ""Horror autotoxicus"", which was initially described by Ehrlich, may not only include autoimmunity to self, it may also encompass immediate hypersensitivity to self, which leads to shock and rapid death.. myelin basic-protein| experimental autoimmune encephalomyelitis| experimental allergic encephalomyelitis| mast-cell degranulation| central-nervous-system| tumor-necrosis-factor| fc-gamma-riii| multiple-sclerosis| t-cells| proteolipid protein."	MAR-2001	myelin basic-protein| experimental autoimmune encephalomyelitis| experimental allergic encephalomyelitis| mast-cell degranulation| central-nervous-system| tumor-necrosis-factor| fc-gamma-riii| multiple-sclerosis| t-cells| proteolipid protein	Pedotti, R; Mitchell, D; Wedemeyer, J; Karpuj, M; Chabas, D; Hattab, EM; Tsai, M; Galli, SJ; Steinman, L	An unexpected version of horror autotoxicus: anaphylactic shock to a self peptide		NATURE IMMUNOLOGY		MYELIN BASIC-PROTEIN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MAST-CELL DEGRANULATION; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; FC-GAMMA-RIII; MULTIPLE-SCLEROSIS; T-CELLS; PROTEOLIPID PROTEIN	"EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypicT helper I (THI) cell-mediated autoimmune disease, it can also be induced by T(H)2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is associated with exposure to a foreign antigen that is often derived from medication, insect venom or food. We report here that, after self-tolerance to myelin is destroyed, anaphylaxis may be triggered by a self-antigen, in this case a myelin peptide. ""Horror autotoxicus"", which was initially described by Ehrlich, may not only include autoimmunity to self, it may also encompass immediate hypersensitivity to self, which leads to shock and rapid death."	55	142	2001	7	10.1038/85266	Immunology
A Nationwide Survey of Patient Centered Medical Home Demonstration Projects. The patient centered medical home has received considerable attention as a potential way to improve primary care quality and limit cost growth. Little information exists that systematically compares PCMH pilot projects across the country. Cross-sectional key-informant interviews. Leaders from existing PCMH demonstration projects with external payment reform. We used a semi-structured interview tool with the following domains: project history, organization and participants, practice requirements and selection process, medical home recognition, payment structure, practice transformation, and evaluation design. A total of 26 demonstrations in 18 states were interviewed. Current demonstrations include over 14,000 physicians caring for nearly 5 million patients. A majority of demonstrations are single payer, and most utilize a three component payment model (traditional fee for service, per person per month fixed payments, and bonus performance payments). The median incremental revenue per physician per year was $22,834 (range $720 to $91,146). Two major practice transformation models were identified-consultative and implementation of the chronic care model. A majority of demonstrations did not have well-developed evaluation plans. Current PCMH demonstration projects with external payment reform include large numbers of patients and physicians as well as a wide spectrum of implementation models. Key questions exist around the adequacy of current payment mechanisms and evaluation plans as public and policy interest in the PCMH model grows.. primary care| physician payment| health reform|chronic care model| community-health centers| quality improvement| internal-medicine| outcomes| disease| asthma.	JUN-2010	primary care| physician payment| health reform|chronic care model| community-health centers| quality improvement| internal-medicine| outcomes| disease| asthma	Bitton, A; Martin, C; Landon, BE	A Nationwide Survey of Patient Centered Medical Home Demonstration Projects		JOURNAL OF GENERAL INTERNAL MEDICINE	primary care; physician payment; health reform	CHRONIC CARE MODEL; COMMUNITY-HEALTH CENTERS; QUALITY IMPROVEMENT; INTERNAL-MEDICINE; OUTCOMES; DISEASE; ASTHMA	The patient centered medical home has received considerable attention as a potential way to improve primary care quality and limit cost growth. Little information exists that systematically compares PCMH pilot projects across the country. Cross-sectional key-informant interviews. Leaders from existing PCMH demonstration projects with external payment reform. We used a semi-structured interview tool with the following domains: project history, organization and participants, practice requirements and selection process, medical home recognition, payment structure, practice transformation, and evaluation design. A total of 26 demonstrations in 18 states were interviewed. Current demonstrations include over 14,000 physicians caring for nearly 5 million patients. A majority of demonstrations are single payer, and most utilize a three component payment model (traditional fee for service, per person per month fixed payments, and bonus performance payments). The median incremental revenue per physician per year was $22,834 (range $720 to $91,146). Two major practice transformation models were identified-consultative and implementation of the chronic care model. A majority of demonstrations did not have well-developed evaluation plans. Current PCMH demonstration projects with external payment reform include large numbers of patients and physicians as well as a wide spectrum of implementation models. Key questions exist around the adequacy of current payment mechanisms and evaluation plans as public and policy interest in the PCMH model grows.	25	141	2010	9	10.1007/s11606-010-1262-8	Health Care Sciences & Services; General & Internal Medicine
Biology and Treatment of Eosinophilic Esophagitis. Eosinophilic esophagitis is a recently recognized but expanding disorder characterized by antigen-driven eosinophil accumulation in the esophagus. Symptoms frequently mimic those of gastroesophageal reflux disease, but the diseases are distinct in their histopathology, gene expression signature, response to therapy, hereditary risk, and association with allergies. The pathogenesis of eosinophilic esophagitis involves environmental and genetic factors, particularly food antigens and expression level of the eosinophil chemoattractant eotaxin-3, respectively. Analyses of gene expression signatures and animal models have indicated the importance of adaptive T-cell immunity that involves interleukin-5 and interleukin-13-induced esophageal epithelial cell responses. Symptoms, dysregulation of esophageal gene expression, and pathology are largely reversible following reduced exposure to specific food antigens as well as anti-inflammatory therapy, but chronic treatment is necessary to prevent relapse. Therefore, eosinophilic esophagitis is a disease with unique features that include chronic esophagitis, atopy, immune sensitization to oral antigens, reversibility, and familial association.. gastroesophageal-reflux disease| anti-il-5 mepolizumab therapy| major basic-protein| celiac-disease| food allergy| skin prick| clinical-features| cationic protein| patch tests| t-cells.	OCT-2009	gastroesophageal-reflux disease| anti-il-5 mepolizumab therapy| major basic-protein| celiac-disease| food allergy| skin prick| clinical-features| cationic protein| patch tests| t-cells	Rothenberg, ME	Biology and Treatment of Eosinophilic Esophagitis		GASTROENTEROLOGY		GASTROESOPHAGEAL-REFLUX DISEASE; ANTI-IL-5 MEPOLIZUMAB THERAPY; MAJOR BASIC-PROTEIN; CELIAC-DISEASE; FOOD ALLERGY; SKIN PRICK; CLINICAL-FEATURES; CATIONIC PROTEIN; PATCH TESTS; T-CELLS	Eosinophilic esophagitis is a recently recognized but expanding disorder characterized by antigen-driven eosinophil accumulation in the esophagus. Symptoms frequently mimic those of gastroesophageal reflux disease, but the diseases are distinct in their histopathology, gene expression signature, response to therapy, hereditary risk, and association with allergies. The pathogenesis of eosinophilic esophagitis involves environmental and genetic factors, particularly food antigens and expression level of the eosinophil chemoattractant eotaxin-3, respectively. Analyses of gene expression signatures and animal models have indicated the importance of adaptive T-cell immunity that involves interleukin-5 and interleukin-13-induced esophageal epithelial cell responses. Symptoms, dysregulation of esophageal gene expression, and pathology are largely reversible following reduced exposure to specific food antigens as well as anti-inflammatory therapy, but chronic treatment is necessary to prevent relapse. Therefore, eosinophilic esophagitis is a disease with unique features that include chronic esophagitis, atopy, immune sensitization to oral antigens, reversibility, and familial association.	134	141	2009	12	10.1053/j.gastro.2009.07.007	Gastroenterology & Hepatology
Nasoseptal flap reconstruction of high flow intraoperative cerebral spinal fluid leaks during endoscopic skull base surgery. Background: Over the past 10 years, significant anatomic, technical, and instrumentation advances have facilitated the exposure and resection of intradural lesions via a fully endoscopic expanded endonasal approach (EEA). The vascularized nasoseptal flap (based on the posterior nasoseptal artery) has become our primary endoscopic reconstructive technique. The goals of this study are to prospectively evaluate the nasoseptal flap and high-risk cerebral spinal fluid (CSF) leak variables. Methods: Prospective evaluation was performed of EEA patients with intraoperative high-flow leaks (either a cistern or ventricle open to nasal cavity during tumor dissection) who underwent nasoseptal flap reconstruction. Results: Seventy consecutive nasoseptal flaps for high-flow intraoperative leaks were evaluated prospectively by the primary author. Twelve risk factors were then graded at the time of the operations and correlated to CSF leak outcomes. The overall postoperative CSF leak rate was 5.7% (4/70). All four postoperative leaks were successfully managed with endoscopic repair and CSF diversion. A multivariate analysis of all 12 risk factors is detailed. Pediatric patients, large dural defects, and radiation therapy were noted to be factors in reconstructive failure. One flap death occurred in a patient with prior surgery and proton therapy, this leak was managed with a temporoparietal flap and endonasal repair. Conclusion: The nasoseptal flap is an excellent anterior skull base reconstructive technique. Patients with high-flow intraoperative CSF leaks had a 94% successful reconstruction rate. Patients with skull base proton radiation therapy are at higher risk for flap failure and preparation for nonradiated tissue reconstruction should be discussed with the patient. (Am J Rhinol Allergy 23, 518-521, 2009; doi: 10.2500/ajra.2009.23.3378). csf leak| endoscopic| meningioma| nasoseptal flap| prognosis| reconstruction| sinonasal tumor| skull base| vascularized flap.	SEP-OCT-2009	csf leak| endoscopic| meningioma| nasoseptal flap| prognosis| reconstruction| sinonasal tumor| skull base| vascularized flap	Zanation, AM; Carrau, RL; Snyderman, CH; Germanwala, AV; Gardner, PA; Prevedello, DM; Kassam, AB	Nasoseptal flap reconstruction of high flow intraoperative cerebral spinal fluid leaks during endoscopic skull base surgery		AMERICAN JOURNAL OF RHINOLOGY & ALLERGY	CSF leak; endoscopic; meningioma; nasoseptal flap; prognosis; reconstruction; sinonasal tumor; skull base; vascularized flap		Background: Over the past 10 years, significant anatomic, technical, and instrumentation advances have facilitated the exposure and resection of intradural lesions via a fully endoscopic expanded endonasal approach (EEA). The vascularized nasoseptal flap (based on the posterior nasoseptal artery) has become our primary endoscopic reconstructive technique. The goals of this study are to prospectively evaluate the nasoseptal flap and high-risk cerebral spinal fluid (CSF) leak variables. Methods: Prospective evaluation was performed of EEA patients with intraoperative high-flow leaks (either a cistern or ventricle open to nasal cavity during tumor dissection) who underwent nasoseptal flap reconstruction. Results: Seventy consecutive nasoseptal flaps for high-flow intraoperative leaks were evaluated prospectively by the primary author. Twelve risk factors were then graded at the time of the operations and correlated to CSF leak outcomes. The overall postoperative CSF leak rate was 5.7% (4/70). All four postoperative leaks were successfully managed with endoscopic repair and CSF diversion. A multivariate analysis of all 12 risk factors is detailed. Pediatric patients, large dural defects, and radiation therapy were noted to be factors in reconstructive failure. One flap death occurred in a patient with prior surgery and proton therapy, this leak was managed with a temporoparietal flap and endonasal repair. Conclusion: The nasoseptal flap is an excellent anterior skull base reconstructive technique. Patients with high-flow intraoperative CSF leaks had a 94% successful reconstruction rate. Patients with skull base proton radiation therapy are at higher risk for flap failure and preparation for nonradiated tissue reconstruction should be discussed with the patient. (Am J Rhinol Allergy 23, 518-521, 2009; doi: 10.2500/ajra.2009.23.3378)	11	141	2009	4	10.2500/ajra.2009.23.3378	Otorhinolaryngology
Risk assessment in anaphylaxis: Current and future approaches. Risk assessment of individuals with anaphylaxis is currently hampered by lack of (1) an optimal and readily available laboratory test to confirm the clinical diagnosis of an anaphylaxis episode and (2) an optimal method of distinguishing allergen-sensitized individuals who are clinically tolerant from those at risk for anaphylaxis episodes after exposure to the relevant allergen. Our objectives were to review the effector mechanisms involved in the pathophysiology of anaphylaxis; to explore the possibility of developing an optimal laboratory test to confirm the diagnosis of an anaphylaxis episode, and the possibility of improving methods to distinguish allergen sensitization from clinical reactivity; and to develop a research agenda for risk assessment in anaphylaxis. Researchers from the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergology and Clinical Immunology held a PRACTALL (Practical Allergy) meeting to discuss these objectives. New approaches being investigated to support the clinical diagnosis of anaphylaxis include serial measurements of total tryptase in serum during an anaphylaxis episode, and measurement of baseline total tryptase levels after the episode. Greater availability of the test for mature beta-tryptase, a more specific mast cell activation marker for anaphylaxis than total tryptase, is needed. Measurement of chymase, mast cell carboxypeptidase A3, platelet-activating factor, and other mast cell products may prove to be useful. Consideration should be given to measuring a panel of mediators from mast cells and basophils. New approaches being investigated to help distinguish sensitized individuals at minimum or no risk from those at increased risk of developing anaphylaxis include measurement of the ratio of allergen-specific IgE to total IgE, determination of IgE directed at specific allergenic epitopes, measurement of basophil activation markers by using flow cytometry, and assessment of allergen-specific cytokine responses. Algorithms have been developed for risk assessment of individuals with anaphylaxis, along with a research agenda for studies that could lead to an improved ability to confirm the clinical diagnosis of anaphylaxis and to identify allergen-sensitized individuals who are at increased risk of anaphylaxis.. anaphylaxis| mast cell| basophil| ige| fc epsilon ri| histamine| tryptase| most cell carboxypeptidase| allergens| insect venom allergy| food allergy|hymenoptera venom allergy| insect-sting challenge| human mast-cells| fc-epsilon-ri| basophil activation test| peanut allergy| food allergy| in-vitro| skin prick| fatal reactions.	JUL-2007	anaphylaxis| mast cell| basophil| ige| fc epsilon ri| histamine| tryptase| most cell carboxypeptidase| allergens| insect venom allergy| food allergy|hymenoptera venom allergy| insect-sting challenge| human mast-cells| fc-epsilon-ri| basophil activation test| peanut allergy| food allergy| in-vitro| skin prick| fatal reactions	Simons, FER; Frew, AJ; Ansotegui, IJ; Bochner, BS; Golden, DBK; Finkelman, FD; Leung, DYM; Lotvall, J; Marone, G; Metcalfe, DD; Muller, U; Rosenwasser, LJ; Sampson, HA; Schwartz, LB; van Hage, M; Walls, AF	Risk assessment in anaphylaxis: Current and future approaches		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	anaphylaxis; mast cell; basophil; IgE; Fc epsilon RI; histamine; tryptase; most cell carboxypeptidase; allergens; insect venom allergy; food allergy	HYMENOPTERA VENOM ALLERGY; INSECT-STING CHALLENGE; HUMAN MAST-CELLS; FC-EPSILON-RI; BASOPHIL ACTIVATION TEST; PEANUT ALLERGY; FOOD ALLERGY; IN-VITRO; SKIN PRICK; FATAL REACTIONS	Risk assessment of individuals with anaphylaxis is currently hampered by lack of (1) an optimal and readily available laboratory test to confirm the clinical diagnosis of an anaphylaxis episode and (2) an optimal method of distinguishing allergen-sensitized individuals who are clinically tolerant from those at risk for anaphylaxis episodes after exposure to the relevant allergen. Our objectives were to review the effector mechanisms involved in the pathophysiology of anaphylaxis; to explore the possibility of developing an optimal laboratory test to confirm the diagnosis of an anaphylaxis episode, and the possibility of improving methods to distinguish allergen sensitization from clinical reactivity; and to develop a research agenda for risk assessment in anaphylaxis. Researchers from the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergology and Clinical Immunology held a PRACTALL (Practical Allergy) meeting to discuss these objectives. New approaches being investigated to support the clinical diagnosis of anaphylaxis include serial measurements of total tryptase in serum during an anaphylaxis episode, and measurement of baseline total tryptase levels after the episode. Greater availability of the test for mature beta-tryptase, a more specific mast cell activation marker for anaphylaxis than total tryptase, is needed. Measurement of chymase, mast cell carboxypeptidase A3, platelet-activating factor, and other mast cell products may prove to be useful. Consideration should be given to measuring a panel of mediators from mast cells and basophils. New approaches being investigated to help distinguish sensitized individuals at minimum or no risk from those at increased risk of developing anaphylaxis include measurement of the ratio of allergen-specific IgE to total IgE, determination of IgE directed at specific allergenic epitopes, measurement of basophil activation markers by using flow cytometry, and assessment of allergen-specific cytokine responses. Algorithms have been developed for risk assessment of individuals with anaphylaxis, along with a research agenda for studies that could lead to an improved ability to confirm the clinical diagnosis of anaphylaxis and to identify allergen-sensitized individuals who are at increased risk of anaphylaxis.	150	141	2007	23	10.1016/j.jaci.2007.05.001	Allergy; Immunology
A regulatory role for the C5a anaphylatoxin in, type 2 immunity in asthma. Complement component 5 (CS) has been described as either promoting or protecting against airway hyper-responsiveness (AHR):in experimental allergic asthma, suggesting pleomorphic effects of C5. Here we report that local pharmacological targeting of the C5a receptor (C5aR) prior to initial allergen sensitization in murine models of inhalation tolerance or allergic asthma resulted in either induction or marked enhancement of Th2-polarized immune responses, airway inflammation, and AHR. Importantly, C5aR-deficient mice exhibited a similar, increased allergic phenotype. Pulmonary allergen exposure in CSaR-targeted mice resulted in increased sensitization and accumulation of CD4(+)CD69(+) T cells associated with a marked increase in pulmonary myeloid, but not plasmacytoid, DC numbers. Pulmonary DCs from C5aR-targeted mice produced large amounts of CC chemokine ligand 17 (CCL17) and CCL22 ex vivo, suggesting a negative impact of C5aR signaling on pulmonary homing of Th2 cells. In contrast, C5aR targeting in sensitized mice led to suppressed airway inflammation and AHR but was still associated with enhanced production of Th2 effector cytokines. These data suggest a dual role for C5a in allergic asthma, i.e., protection from the development of maladaptive type 2 immune responses during allergen sensitization at the DC/T cell interface but enhancement of airway inflammation and AHR in an established inflammatory environment.. induced airway hyperresponsiveness| plasmacytoid dendritic cells| ischemia-reperfusion injury| th2 effector functions| genome-wide search| allergic-asthma| inhaled antigen| cutting edge| in-vivo| c3a anaphylatoxin.	MAR-2006	induced airway hyperresponsiveness| plasmacytoid dendritic cells| ischemia-reperfusion injury| th2 effector functions| genome-wide search| allergic-asthma| inhaled antigen| cutting edge| in-vivo| c3a anaphylatoxin	Kohl, J; Baelder, R; Lewkowich, IP; Pandey, MK; Hawlisch, H; Wang, LH; Best, J; Herman, NS; Sproles, AA; Zwirner, J; Whitsett, JA; Gerard, C; Sfyroera, G; Lambris, JD; Wills-Karp, M	A regulatory role for the C5a anaphylatoxin in, type 2 immunity in asthma		JOURNAL OF CLINICAL INVESTIGATION		INDUCED AIRWAY HYPERRESPONSIVENESS; PLASMACYTOID DENDRITIC CELLS; ISCHEMIA-REPERFUSION INJURY; TH2 EFFECTOR FUNCTIONS; GENOME-WIDE SEARCH; ALLERGIC-ASTHMA; INHALED ANTIGEN; CUTTING EDGE; IN-VIVO; C3A ANAPHYLATOXIN	Complement component 5 (CS) has been described as either promoting or protecting against airway hyper-responsiveness (AHR):in experimental allergic asthma, suggesting pleomorphic effects of C5. Here we report that local pharmacological targeting of the C5a receptor (C5aR) prior to initial allergen sensitization in murine models of inhalation tolerance or allergic asthma resulted in either induction or marked enhancement of Th2-polarized immune responses, airway inflammation, and AHR. Importantly, C5aR-deficient mice exhibited a similar, increased allergic phenotype. Pulmonary allergen exposure in CSaR-targeted mice resulted in increased sensitization and accumulation of CD4(+)CD69(+) T cells associated with a marked increase in pulmonary myeloid, but not plasmacytoid, DC numbers. Pulmonary DCs from C5aR-targeted mice produced large amounts of CC chemokine ligand 17 (CCL17) and CCL22 ex vivo, suggesting a negative impact of C5aR signaling on pulmonary homing of Th2 cells. In contrast, C5aR targeting in sensitized mice led to suppressed airway inflammation and AHR but was still associated with enhanced production of Th2 effector cytokines. These data suggest a dual role for C5a in allergic asthma, i.e., protection from the development of maladaptive type 2 immune responses during allergen sensitization at the DC/T cell interface but enhancement of airway inflammation and AHR in an established inflammatory environment.	64	141	2006	14	10.1172/JCI26582	Research & Experimental Medicine
Modeling allergic asthma in mice - Pitfalls and opportunities. Studies in murine experimental models have contributed greatly to understanding the mechanisms of allergic inflammation underlying asthma. However, models involving short-term high-level exposure of sensitized animals to antigen have significant limitations for investigating the pathogenesis of the lesions of chronic asthma. Modeling chronic asthma is problematic, because long-term antigenic challenge often triggers widespread pulmonary parenchymal inflammation or leads to eventual downregulation of inflammation and airway hyperreactivity. We have developed an improved murine model in which animals are exposed to low mass concentrations of aerosolized antigen for 6-8 wk. The mice exhibit airway-specific acute-on-chronic inflammation and changes of airway wall remodeling as seen in human asthma, together with hyperreactivity to a cholinergic agonist which can be specifically attributed to airway disease. This more realistic model of asthma offers a number of opportunities for investigation of pathogenetic mechanisms and novel therapeutic agents.. induced airway hyperreactivity| antigen-induced eosinophil| goblet cell hyperplasia| murine model| mouse models| bronchial hyperresponsiveness| transgenic mice| lung damage| t-cells| immunological-tolerance.	SEP-2002	induced airway hyperreactivity| antigen-induced eosinophil| goblet cell hyperplasia| murine model| mouse models| bronchial hyperresponsiveness| transgenic mice| lung damage| t-cells| immunological-tolerance	Kumar, RK; Foster, PS	Modeling allergic asthma in mice - Pitfalls and opportunities		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		INDUCED AIRWAY HYPERREACTIVITY; ANTIGEN-INDUCED EOSINOPHIL; GOBLET CELL HYPERPLASIA; MURINE MODEL; MOUSE MODELS; BRONCHIAL HYPERRESPONSIVENESS; TRANSGENIC MICE; LUNG DAMAGE; T-CELLS; IMMUNOLOGICAL-TOLERANCE	Studies in murine experimental models have contributed greatly to understanding the mechanisms of allergic inflammation underlying asthma. However, models involving short-term high-level exposure of sensitized animals to antigen have significant limitations for investigating the pathogenesis of the lesions of chronic asthma. Modeling chronic asthma is problematic, because long-term antigenic challenge often triggers widespread pulmonary parenchymal inflammation or leads to eventual downregulation of inflammation and airway hyperreactivity. We have developed an improved murine model in which animals are exposed to low mass concentrations of aerosolized antigen for 6-8 wk. The mice exhibit airway-specific acute-on-chronic inflammation and changes of airway wall remodeling as seen in human asthma, together with hyperreactivity to a cholinergic agonist which can be specifically attributed to airway disease. This more realistic model of asthma offers a number of opportunities for investigation of pathogenetic mechanisms and novel therapeutic agents.	77	141	2002	6	10.1165/rcmb.F248	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Metals and women's health. There is a lack of information concerning whether environmental-related health effects are more or less prevalent or manifested differently in women compared to men. Previously, most research in the area of toxicology and environmental and occupational health involved male subjects. The present work aims at reviewing exposure and health effects of cadmium, nickel, lead, mercury, and arsenic manifested differently in women than in men. The gender difference in exposure to nickel results in a much higher prevalence of nickel allergy and hand eczema in women than in men. The internal cadmium dose is generally higher in women than in men, due to a higher gastrointestinal absorption at low iron stores. This was probably one major reason why Itai-itai disease was mainly a woman's disease. Yet, data are sparse regarding the risk for women relative to men to develop cadmium-induced kidney damage in populations exposed to low levels of cadmium. Lead is accumulated mainly in bone and increased endogenous lead exposure has been demonstrated in women during periods of increased bone turnover, e.g., menopause. Both lead and mercury exposure in pregnant women has to be kept low in order to prevent neurodevelopment effects in the developing fetus and child. Limited data indicate that women are more affected than men following exposure to methylmercury at adult age, while males seem to be more sensitive to exposure during early development. Regarding arsenic, some data indicate gender differences in the biotransformation by methylation, possibly also in susceptibility to certain arsenic-related cancers. Obviously, gender-related differences in exposure and health effects caused by metals are highly neglected research areas, which need considerable focus in the future. (C) 2002 Elsevier Science (USA).. blood lead levels| environmental cadmium exposure| japanese general-population| nutrient-sufficient diet| drinking-water| cognitive function| postmenopausal women| contact-dermatitis| osteoblastic cells| mercury exposure.	MAR-2002	blood lead levels| environmental cadmium exposure| japanese general-population| nutrient-sufficient diet| drinking-water| cognitive function| postmenopausal women| contact-dermatitis| osteoblastic cells| mercury exposure	Vahter, M; Berglund, M; Akesson, A; Liden, C	Metals and women's health		ENVIRONMENTAL RESEARCH		BLOOD LEAD LEVELS; ENVIRONMENTAL CADMIUM EXPOSURE; JAPANESE GENERAL-POPULATION; NUTRIENT-SUFFICIENT DIET; DRINKING-WATER; COGNITIVE FUNCTION; POSTMENOPAUSAL WOMEN; CONTACT-DERMATITIS; OSTEOBLASTIC CELLS; MERCURY EXPOSURE	There is a lack of information concerning whether environmental-related health effects are more or less prevalent or manifested differently in women compared to men. Previously, most research in the area of toxicology and environmental and occupational health involved male subjects. The present work aims at reviewing exposure and health effects of cadmium, nickel, lead, mercury, and arsenic manifested differently in women than in men. The gender difference in exposure to nickel results in a much higher prevalence of nickel allergy and hand eczema in women than in men. The internal cadmium dose is generally higher in women than in men, due to a higher gastrointestinal absorption at low iron stores. This was probably one major reason why Itai-itai disease was mainly a woman's disease. Yet, data are sparse regarding the risk for women relative to men to develop cadmium-induced kidney damage in populations exposed to low levels of cadmium. Lead is accumulated mainly in bone and increased endogenous lead exposure has been demonstrated in women during periods of increased bone turnover, e.g., menopause. Both lead and mercury exposure in pregnant women has to be kept low in order to prevent neurodevelopment effects in the developing fetus and child. Limited data indicate that women are more affected than men following exposure to methylmercury at adult age, while males seem to be more sensitive to exposure during early development. Regarding arsenic, some data indicate gender differences in the biotransformation by methylation, possibly also in susceptibility to certain arsenic-related cancers. Obviously, gender-related differences in exposure and health effects caused by metals are highly neglected research areas, which need considerable focus in the future. (C) 2002 Elsevier Science (USA).	115	141	2002	11	10.1006/enrs.2002.4338	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Why are allergies increasing?. The incidence of atopic allergy is increasing in certain 'Western' countries but this remains unexplained. Various hypotheses with differing amounts of evidence and/or relevance have been assessed, including increased awareness of the diseases, improved diagnostics, genetic susceptibility, psycho-social influences, allergen exposure, decreased immune-system stimulation, underlying disease, anti-allergic therapy and pollution.. house-dust mite| immunoglobulin-e| air-pollution| atopic eczema| hay-fever| life-style| children| asthma| prevalence| childhood.	DEC-2001	house-dust mite| immunoglobulin-e| air-pollution| atopic eczema| hay-fever| life-style| children| asthma| prevalence| childhood	Ring, J; Kramer, U; Schafer, T; Behrendt, H	Why are allergies increasing?		CURRENT OPINION IN IMMUNOLOGY		HOUSE-DUST MITE; IMMUNOGLOBULIN-E; AIR-POLLUTION; ATOPIC ECZEMA; HAY-FEVER; LIFE-STYLE; CHILDREN; ASTHMA; PREVALENCE; CHILDHOOD	The incidence of atopic allergy is increasing in certain 'Western' countries but this remains unexplained. Various hypotheses with differing amounts of evidence and/or relevance have been assessed, including increased awareness of the diseases, improved diagnostics, genetic susceptibility, psycho-social influences, allergen exposure, decreased immune-system stimulation, underlying disease, anti-allergic therapy and pollution.	64	141	2001	8	10.1016/S0952-7915(01)00282-5	Immunology
Recombinant allergens for diagnosis and therapy of allergic disease. Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome with use of genetically engineered recombinant allergens. Over the past 10 years, the most important allergens from mites, pollens, animal dander, insects, and foods have been cloned, sequenced, and expressed. In many cases the three-dimensional allergen structure has been determined and B-cell and T-cell epitopes have been mapped. These studies show that allergens have diverse biologic functions (they may be enzymes, enzyme inhibitors, lipocalins, or structural proteins) and that as a rule the allergen function is unrelated to its ability to cause IgE antibody responses, High-level expression systems have been developed to produce recombinant allergens in bacteria, yeast, or insect cells. Recombinant allergens show comparable IgE antibody binding to their natural counterparts (where available) and show excellent reactivity on skin testing and in in vitro diagnostic tests. Cocktails of recombinant allergens can be formulated with predetermined and uniform allergen levels, which could replace natural allergens and result in the development of innovative, patient-based tests for allergy diagnosis. Recombinant allergens also offer the exciting possibility of developing new forms of allergen immunotherapy, including the use of hypoallergens, allergens coupled to IgE suppressive adjuvants, and peptide-based therapies. The production of recombinant allergens as defined molecular entities makes it feasible to consider the possibility of developing prophylactic allergen vaccines. The introduction of recombinant allergens in research and in clinical trials should lead to significant improvements in allergy diagnosis and treatment.. recombinant allergens| mites| animal allergens| allergy diagnostics| allergy therapeutics| asthma| allergy vaccines| allergen immunotherapy|house-dust-mite| der-p-i| cross-reactive allergen| high-level expression| ige-binding| pichia-pastoris| molecular-cloning| major allergen| x-ray| dermatophagoides-pteronyssinus.	SEP-2000	recombinant allergens| mites| animal allergens| allergy diagnostics| allergy therapeutics| asthma| allergy vaccines| allergen immunotherapy|house-dust-mite| der-p-i| cross-reactive allergen| high-level expression| ige-binding| pichia-pastoris| molecular-cloning| major allergen| x-ray| dermatophagoides-pteronyssinus	Chapman, MD; Smith, AM; Vailes, LD; Arruda, LK; Dhanaraj, V; Pomes, A	Recombinant allergens for diagnosis and therapy of allergic disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	recombinant allergens; mites; animal allergens; allergy diagnostics; allergy therapeutics; asthma; allergy vaccines; allergen immunotherapy	HOUSE-DUST-MITE; DER-P-I; CROSS-REACTIVE ALLERGEN; HIGH-LEVEL EXPRESSION; IGE-BINDING; PICHIA-PASTORIS; MOLECULAR-CLONING; MAJOR ALLERGEN; X-RAY; DERMATOPHAGOIDES-PTERONYSSINUS	Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome with use of genetically engineered recombinant allergens. Over the past 10 years, the most important allergens from mites, pollens, animal dander, insects, and foods have been cloned, sequenced, and expressed. In many cases the three-dimensional allergen structure has been determined and B-cell and T-cell epitopes have been mapped. These studies show that allergens have diverse biologic functions (they may be enzymes, enzyme inhibitors, lipocalins, or structural proteins) and that as a rule the allergen function is unrelated to its ability to cause IgE antibody responses, High-level expression systems have been developed to produce recombinant allergens in bacteria, yeast, or insect cells. Recombinant allergens show comparable IgE antibody binding to their natural counterparts (where available) and show excellent reactivity on skin testing and in in vitro diagnostic tests. Cocktails of recombinant allergens can be formulated with predetermined and uniform allergen levels, which could replace natural allergens and result in the development of innovative, patient-based tests for allergy diagnosis. Recombinant allergens also offer the exciting possibility of developing new forms of allergen immunotherapy, including the use of hypoallergens, allergens coupled to IgE suppressive adjuvants, and peptide-based therapies. The production of recombinant allergens as defined molecular entities makes it feasible to consider the possibility of developing prophylactic allergen vaccines. The introduction of recombinant allergens in research and in clinical trials should lead to significant improvements in allergy diagnosis and treatment.	91	141	2000	10		Allergy; Immunology
Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families. Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, me conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed signficant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MILS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups. (C) 2000 Academic Press.. total serum ige| il-4 gene-expression| bronchial hyperresponsiveness| underlying asthma| allergic-asthma| relative risks| major gene| nf-y| markers| responsiveness.	JUN 1-2000	total serum ige| il-4 gene-expression| bronchial hyperresponsiveness| underlying asthma| allergic-asthma| relative risks| major gene| nf-y| markers| responsiveness	Yokouchi, Y; Nukaga, Y; Shibasaki, M; Noguchi, E; Kimura, K; Ito, S; Nishihara, M; Yamakawa-Kobayashi, K; Takeda, K; Imoto, N; Ichikawa, K; Matsui, A; Hamaguchi, H; Arinami, T	Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families		GENOMICS		TOTAL SERUM IGE; IL-4 GENE-EXPRESSION; BRONCHIAL HYPERRESPONSIVENESS; UNDERLYING ASTHMA; ALLERGIC-ASTHMA; RELATIVE RISKS; MAJOR GENE; NF-Y; MARKERS; RESPONSIVENESS	Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, me conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed signficant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MILS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups. (C) 2000 Academic Press.	47	141	2000	9	10.1006/geno.2000.6201	Biotechnology & Applied Microbiology; Genetics & Heredity
Asthma. Asthma is a heterogeneous group of conditions that result in recurrent, reversible bronchial obstruction. Although the disease can start at any age, the first symptoms occur during childhood in most cases. Asthma has a strong genetic component, and genome-wide association studies have identified variations in several genes that slightly increase the risk of disease. Asthma is often associated with increased susceptibility to infection with rhinoviruses and with changes in the composition of microbial communities colonising the airways, but whether these changes are a cause or consequence of the disease is unknown. There is currently no proven prevention strategy; however, the finding that exposure to microbial products in early life, particularly in farming environments, seems to be protective against asthma offers hope that surrogates of such exposure could be used to prevent the disease. Genetic and immunological studies point to defective responses of lung resident cells, especially those associated with the mucosal epithelium, as crucial elements in the pathogenesis of asthma. Inhaled corticosteroids continue to be the mainstay for the treatment of mild and moderate asthma, but limited adherence to daily inhaled medication is a major obstacle to the success of such therapy. Severe asthma that is refractory to usual treatment continues to be a challenge, but new biological therapies, such as humanised antibodies against IgE, interleukin 5, and interleukin 13, off er hope to improve the quality of life and long-term prognosis of severe asthmatics with specific molecular phenotypes.. innate lymphoid-cells| mild persistent asthma| regulatory t-cells| intermittent inhaled corticosteroids| randomized controlled-trial| placebo-controlled trial| genome-wide association| acting beta-agonists| step-up therapy| childhood asthma.	OCT 19-2013	innate lymphoid-cells| mild persistent asthma| regulatory t-cells| intermittent inhaled corticosteroids| randomized controlled-trial| placebo-controlled trial| genome-wide association| acting beta-agonists| step-up therapy| childhood asthma	Martinez, FD; Vercelli, D	Asthma		LANCET		INNATE LYMPHOID-CELLS; MILD PERSISTENT ASTHMA; REGULATORY T-CELLS; INTERMITTENT INHALED CORTICOSTEROIDS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; GENOME-WIDE ASSOCIATION; ACTING BETA-AGONISTS; STEP-UP THERAPY; CHILDHOOD ASTHMA	Asthma is a heterogeneous group of conditions that result in recurrent, reversible bronchial obstruction. Although the disease can start at any age, the first symptoms occur during childhood in most cases. Asthma has a strong genetic component, and genome-wide association studies have identified variations in several genes that slightly increase the risk of disease. Asthma is often associated with increased susceptibility to infection with rhinoviruses and with changes in the composition of microbial communities colonising the airways, but whether these changes are a cause or consequence of the disease is unknown. There is currently no proven prevention strategy; however, the finding that exposure to microbial products in early life, particularly in farming environments, seems to be protective against asthma offers hope that surrogates of such exposure could be used to prevent the disease. Genetic and immunological studies point to defective responses of lung resident cells, especially those associated with the mucosal epithelium, as crucial elements in the pathogenesis of asthma. Inhaled corticosteroids continue to be the mainstay for the treatment of mild and moderate asthma, but limited adherence to daily inhaled medication is a major obstacle to the success of such therapy. Severe asthma that is refractory to usual treatment continues to be a challenge, but new biological therapies, such as humanised antibodies against IgE, interleukin 5, and interleukin 13, off er hope to improve the quality of life and long-term prognosis of severe asthmatics with specific molecular phenotypes.	159	140	2013	13	10.1016/S0140-6736(13)61536-6	General & Internal Medicine
Pre-operative computed tomography coronary anglography to detect significant coronary artery disease in patients referred for cardiac valve surgery. OBJECTIVES We studied the diagnostic performance of 64-slice computed tomography coronary angiography (CTCA) to rule out or detect significant coronary stenosis in patients referred for valve surgery. BACKGROUND Invasive conventional coronary angiography (CCA) is recommended in most patients scheduled for valve surgery. METHODS During a 6-month period, 145 patients were prospectively identified from a consecutive patient population scheduled for valve surgery. Thirty-five patients were excluded because of CTCA criteria: irregular heart rhythm (n = 26), impaired renal function (n = 5), and known contrast allergy (n = 4). General exclusion criteria were: hospitalization in community hospital (n = 4), no need for CCA (n = 4), previous coronary artery bypass surgery (n = 1), or percutaneous coronary intervention (n = 4). Of the remaining 97 patients, 27 denied written informed consent. Thus, the study population comprised 70 patients (49 male, 21 female;, mean age 63 +/- 11 years). RESULTS Prevalence of significant coronary artery disease, defined as having at least 1 >= 50% stenosis per patient, was 25.7%. Beta-blockers were administered in 71%, and 64% received lorazepam. The mean heart rate dropped from 72.5 +/- 12.4 to 59.5 +/- 7.5 beats/min. The mean scan time was 12.8 +/- 1.3 s. On a per-patient analysis, the sensitivity, specificity, and positive and negative predictive values were: 100% (18 of 18; 95% confidence interval [CI] 78 to 100), 92% (48 of 52; 95% CI 81 to 98), 82% (18 of 22; 95% CI 59 to 94), and 100% (48 of 48; 95% CI 91 to 100), respectively. CONCLUSIONS The diagnostic accuracy of 64-slice CTCA for ruling out the presence of significant coronary stenoses in patients undergoing valve surgery is excellent and allows CTCA implementation as a gatekeeper for invasive CCA in these patients.. valvular heart-disease| practice guidelines committee| association task-force| aortic-stenosis| radiation-exposure| angina-pectoris| angiography| accuracy| ct| quantification.	OCT 17-2006	valvular heart-disease| practice guidelines committee| association task-force| aortic-stenosis| radiation-exposure| angina-pectoris| angiography| accuracy| ct| quantification	Meijboom, WB; Mollet, NR; Van Mieghem, CAG; Kluin, J; Weustink, AC; Pugliese, F; Vourvouri, E; Cademartiri, F; Bogers, AJJC; Krestin, GP; de Feyter, PJ	Pre-operative computed tomography coronary anglography to detect significant coronary artery disease in patients referred for cardiac valve surgery		JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY		VALVULAR HEART-DISEASE; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; AORTIC-STENOSIS; RADIATION-EXPOSURE; ANGINA-PECTORIS; ANGIOGRAPHY; ACCURACY; CT; QUANTIFICATION	OBJECTIVES We studied the diagnostic performance of 64-slice computed tomography coronary angiography (CTCA) to rule out or detect significant coronary stenosis in patients referred for valve surgery. BACKGROUND Invasive conventional coronary angiography (CCA) is recommended in most patients scheduled for valve surgery. METHODS During a 6-month period, 145 patients were prospectively identified from a consecutive patient population scheduled for valve surgery. Thirty-five patients were excluded because of CTCA criteria: irregular heart rhythm (n = 26), impaired renal function (n = 5), and known contrast allergy (n = 4). General exclusion criteria were: hospitalization in community hospital (n = 4), no need for CCA (n = 4), previous coronary artery bypass surgery (n = 1), or percutaneous coronary intervention (n = 4). Of the remaining 97 patients, 27 denied written informed consent. Thus, the study population comprised 70 patients (49 male, 21 female;, mean age 63 +/- 11 years). RESULTS Prevalence of significant coronary artery disease, defined as having at least 1 >= 50% stenosis per patient, was 25.7%. Beta-blockers were administered in 71%, and 64% received lorazepam. The mean heart rate dropped from 72.5 +/- 12.4 to 59.5 +/- 7.5 beats/min. The mean scan time was 12.8 +/- 1.3 s. On a per-patient analysis, the sensitivity, specificity, and positive and negative predictive values were: 100% (18 of 18; 95% confidence interval [CI] 78 to 100), 92% (48 of 52; 95% CI 81 to 98), 82% (18 of 22; 95% CI 59 to 94), and 100% (48 of 48; 95% CI 91 to 100), respectively. CONCLUSIONS The diagnostic accuracy of 64-slice CTCA for ruling out the presence of significant coronary stenoses in patients undergoing valve surgery is excellent and allows CTCA implementation as a gatekeeper for invasive CCA in these patients.	29	140	2006	8	10.1016/j.jacc.2006.06.054	Cardiovascular System & Cardiology
Metal-rich ambient particles (Particulate Matter(2.5)) cause airway inflammation in healthy subjects. Epidemiologic studies have shown an increased prevalence of allergic asthma in children living in a German smelter area (Hettstedt) compared with a cohort who live in a nonindustrialized area (Zerbst). However, it is not known whether ambient particles (particulate matter(2.5) [PM2.5]) from these areas induce distinct lung inflammation, which might be an explanation for this difference. Therefore, 100 mug of PM2.5 suspensions, collected simultaneously in the two areas, were instilled through a bronchoscope into contralateral lung segments of 12 healthy volunteers. PM2.5 from both Hettstedt and Zerbst increased the number of leukocytes in the bronchoalveolar lavage performed 24 hours later. PM2.5 from Hettstedt, but not Zerbst, induced a significant influx of monocytes (Hettstedt: 7.0% vs. Zerbst: 4.3%) without influencing the expression of surface activation markers on monocytes and alveolar macrophages. Oxidant radical generation of bronchoalveolar lavage cells and cytokine concentration (interieukin-6 and tumor necrosis factor-alpha) in bronchoalveolar lavage fluid was significantly increased after instillation of Hettstedt PM2.5. We conclude that environmentally relevant concentrations of PM2.5 from the smelter area induced distinct airway inflammation in healthy subjects with a selective influx of monocytes and increased generation of oxidant radicals. The higher concentration of transition metals in PM2.5 from Hettstedt might be responsible for this increased inflammation.. air pollution| bronchoscopy| monocytes| oxidants|respiratory symptoms| east-germany| pollution| lung| children| disease| pm2.5| instillation| phenotype| endotoxin.	OCT 15-2004	air pollution| bronchoscopy| monocytes| oxidants|respiratory symptoms| east-germany| pollution| lung| children| disease| pm2.5| instillation| phenotype| endotoxin	Schaumann, F; Borm, PJA; Herbrich, A; Knoch, J; Pitz, M; Schins, RPF; Luettig, B; Hohlfeld, JM; Heinrich, J; Krug, N	Metal-rich ambient particles (Particulate Matter(2.5)) cause airway inflammation in healthy subjects		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	air pollution; bronchoscopy; monocytes; oxidants	RESPIRATORY SYMPTOMS; EAST-GERMANY; POLLUTION; LUNG; CHILDREN; DISEASE; PM2.5; INSTILLATION; PHENOTYPE; ENDOTOXIN	Epidemiologic studies have shown an increased prevalence of allergic asthma in children living in a German smelter area (Hettstedt) compared with a cohort who live in a nonindustrialized area (Zerbst). However, it is not known whether ambient particles (particulate matter(2.5) [PM2.5]) from these areas induce distinct lung inflammation, which might be an explanation for this difference. Therefore, 100 mug of PM2.5 suspensions, collected simultaneously in the two areas, were instilled through a bronchoscope into contralateral lung segments of 12 healthy volunteers. PM2.5 from both Hettstedt and Zerbst increased the number of leukocytes in the bronchoalveolar lavage performed 24 hours later. PM2.5 from Hettstedt, but not Zerbst, induced a significant influx of monocytes (Hettstedt: 7.0% vs. Zerbst: 4.3%) without influencing the expression of surface activation markers on monocytes and alveolar macrophages. Oxidant radical generation of bronchoalveolar lavage cells and cytokine concentration (interieukin-6 and tumor necrosis factor-alpha) in bronchoalveolar lavage fluid was significantly increased after instillation of Hettstedt PM2.5. We conclude that environmentally relevant concentrations of PM2.5 from the smelter area induced distinct airway inflammation in healthy subjects with a selective influx of monocytes and increased generation of oxidant radicals. The higher concentration of transition metals in PM2.5 from Hettstedt might be responsible for this increased inflammation.	22	140	2004	6	10.1164/rccm.200403-423OC	General & Internal Medicine; Respiratory System
Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. Background: Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids. Although house dust mite allergen avoidance has been used as a preventive strategy in several trials, the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known. Objective: To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma. Methods: A total of 616 children at high risk of asthma were enrolled antenatally in a randomized controlled trial, and 526 children remained in the trial at age 3 years. The outcomes were symptoms of allergic disease and allergen sensitization. Results: There was a significant 10.0% (95% CI, 3.7-16.4) reduction in the prevalence of cough in atopic children in the active diet group (P = .003; number needed to treat, 10) but a negligible 1.1 % (95 % CI, -7.1 to 9.5) reduction cough among nonatopic children. There was a 7.2% (95% CI, 10.11-14.3) reduction in sensitization to house dust mite in the active allergen avoidance group (P = .05; number needed to treat, 14). No significant differences in wheeze were found with either intervention. Conclusion: These results suggest that our interventions, designed to be used in simple public health campaigns, may have a role in preventing the development of allergic sensitization and airways disease in early childhood. This offers the prospect of reducing allergic disease in later life.. allergen avoidance| allergy| asthma| atopy| omega-3 fatty acids| house dust mite| primary prevention|respiratory symptoms| randomized trial| high-risk| fish-oil| atopy| cough| intervention| avoidance| pregnancy| infants.	OCT-2004	allergen avoidance| allergy| asthma| atopy| omega-3 fatty acids| house dust mite| primary prevention|respiratory symptoms| randomized trial| high-risk| fish-oil| atopy| cough| intervention| avoidance| pregnancy| infants	Peat, JK; Mihrshahi, S; Kemp, AS; Marks, GB; Tovey, ER; Webb, K; Mellis, CM; Leeder, SR	Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen avoidance; allergy; asthma; atopy; omega-3 fatty acids; house dust mite; primary prevention	RESPIRATORY SYMPTOMS; RANDOMIZED TRIAL; HIGH-RISK; FISH-OIL; ATOPY; COUGH; INTERVENTION; AVOIDANCE; PREGNANCY; INFANTS	Background: Two factors thought to influence the risk of asthma are the promoting effect of sensitization to house dust mites and the preventive effect of increased omega-3 fatty acids. Although house dust mite allergen avoidance has been used as a preventive strategy in several trials, the effect of omega-3 fatty acid supplementation in the primary prevention of asthma and allergic disease is not known. Objective: To measure the effects of dietary supplementation with omega-3 fatty acids and house dust mite allergen avoidance in children with a family history of asthma. Methods: A total of 616 children at high risk of asthma were enrolled antenatally in a randomized controlled trial, and 526 children remained in the trial at age 3 years. The outcomes were symptoms of allergic disease and allergen sensitization. Results: There was a significant 10.0% (95% CI, 3.7-16.4) reduction in the prevalence of cough in atopic children in the active diet group (P = .003; number needed to treat, 10) but a negligible 1.1 % (95 % CI, -7.1 to 9.5) reduction cough among nonatopic children. There was a 7.2% (95% CI, 10.11-14.3) reduction in sensitization to house dust mite in the active allergen avoidance group (P = .05; number needed to treat, 14). No significant differences in wheeze were found with either intervention. Conclusion: These results suggest that our interventions, designed to be used in simple public health campaigns, may have a role in preventing the development of allergic sensitization and airways disease in early childhood. This offers the prospect of reducing allergic disease in later life.	31	140	2004	7	10.1016/j.jaci.2004.06.057	Allergy; Immunology
Allergic cross-reactivity: from gene to the clinic. A large number of allergenic proteins have now their complete cDNA sequences determined and in some cases also the 3D structures. It turned out that most allergens could be grouped into a small number of structural protein families, regardless of their biological source. Structural similarity among proteins from diverse sources is the molecular basis of allergic cross-reactivity. The clinical relevance of immunoglobulin E (IgE) cross-reactivity seems to be influenced by a number of factors including the immune response against the allergen, exposure and the allergen. As individuals are exposed to a variable number of allergenic sources bearing homologous molecules, the exact nature of the antigenic structure inducing the primary IgE immune response cannot be easily defined. In general, the 'cross-reactivity' term should be limited to defined clinical manifestations showing reactivity to a source without previous exposure. 'Co-recognition', including by definition 'cross-reactivity', could be used to describe the large majority of the IgE reactivity where co-exposure to a number of sources bearing homologous molecules do not allow unequivocal identification of the sensitizing molecule. The analysis of reactivity clusters in diagnosis allows the interpretation of the patient's reactivity profile as a result of the sensitization process, which often begins with exposure to a single allergenic molecule.. allergen structure| allergenicity| arthropod allergens| cross-reactive carbohydrate determinant| cross-reactivity| food allergens| immunoglobulin e antibodies| insect venom allergens| latex allergens| pollen allergens|ige-binding epitopes| grass-pollen allergen| house-dust mite| bet v 1| controlled food challenge| major cherry allergen| latex-fruit syndrome| cows milk allergy| bird-egg syndrome| peanut allergy.	MAR-2004	allergen structure| allergenicity| arthropod allergens| cross-reactive carbohydrate determinant| cross-reactivity| food allergens| immunoglobulin e antibodies| insect venom allergens| latex allergens| pollen allergens|ige-binding epitopes| grass-pollen allergen| house-dust mite| bet v 1| controlled food challenge| major cherry allergen| latex-fruit syndrome| cows milk allergy| bird-egg syndrome| peanut allergy	Ferreira, F; Hawranek, T; Gruber, P; Wopfner, N; Mari, A	Allergic cross-reactivity: from gene to the clinic		ALLERGY	allergen structure; allergenicity; arthropod allergens; cross-reactive carbohydrate determinant; cross-reactivity; food allergens; immunoglobulin E antibodies; insect venom allergens; latex allergens; pollen allergens	IGE-BINDING EPITOPES; GRASS-POLLEN ALLERGEN; HOUSE-DUST MITE; BET V 1; CONTROLLED FOOD CHALLENGE; MAJOR CHERRY ALLERGEN; LATEX-FRUIT SYNDROME; COWS MILK ALLERGY; BIRD-EGG SYNDROME; PEANUT ALLERGY	A large number of allergenic proteins have now their complete cDNA sequences determined and in some cases also the 3D structures. It turned out that most allergens could be grouped into a small number of structural protein families, regardless of their biological source. Structural similarity among proteins from diverse sources is the molecular basis of allergic cross-reactivity. The clinical relevance of immunoglobulin E (IgE) cross-reactivity seems to be influenced by a number of factors including the immune response against the allergen, exposure and the allergen. As individuals are exposed to a variable number of allergenic sources bearing homologous molecules, the exact nature of the antigenic structure inducing the primary IgE immune response cannot be easily defined. In general, the 'cross-reactivity' term should be limited to defined clinical manifestations showing reactivity to a source without previous exposure. 'Co-recognition', including by definition 'cross-reactivity', could be used to describe the large majority of the IgE reactivity where co-exposure to a number of sources bearing homologous molecules do not allow unequivocal identification of the sensitizing molecule. The analysis of reactivity clusters in diagnosis allows the interpretation of the patient's reactivity profile as a result of the sensitization process, which often begins with exposure to a single allergenic molecule.	219	140	2004	25	10.1046/j.1398-9995.2003.00407.x	Allergy; Immunology
Prolonged allergen challenge in mice leads to persistent airway remodelling. Background Inflammatory infiltrates, airway hyper-responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen-induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features. Objective The aim of this study was to use a murine model of prolonged allergen-induced airway inflammation in order to characterize the cells and molecules involved in the ensuing airway remodelling. Moreover, we investigated whether remodelling persists in the absence of continued allergen challenge. Methods Acute pulmonary eosinophilia and airways hyper-reactivity were induced after six serial allergen challenges in sensitized mice (acute phase). Mice were subsequently challenged three times a week with ovalbumin (OVA) (chronic phase) up to day 55. To investigate the persistence of pathology, one group of mice were left for another 4 weeks without further allergen challenge (day 80). Results The extended OVA challenge protocol caused significant airway remodelling, which was absent in the acute phase. Specifically, remodelling was characterized by deposition of collagen as well as airway smooth muscle and goblet cell hyperplasia. Importantly, these airway changes, together with tissue eosinophilia were sustained in the absence of further allergen challenge. Examination of cytokines revealed a dramatic up-regulation of IL-4 and tumour growth factor-beta1 during the chronic phase. Interestingly, while IL-4 levels were significantly increased during the chronic phase, levels of IL-13 fell. Levels of the Th1-associated cytokine IFN-gamma also increased during the chronic phase. Conclusion In conclusion, we have demonstrated that prolonged allergen challenge results in persistent airway wall remodelling.. airway remodelling| allergic airway inflammation| asthma| eosinophils| th2 cytokines|bronchial epithelial-cells| mouse asthma model| growth-factor-beta| murine model| subepithelial fibrosis| interferon-gamma| transforming growth-factor-beta-1| gene-expression| atopic asthma| in-vitro.	MAR-2004	airway remodelling| allergic airway inflammation| asthma| eosinophils| th2 cytokines|bronchial epithelial-cells| mouse asthma model| growth-factor-beta| murine model| subepithelial fibrosis| interferon-gamma| transforming growth-factor-beta-1| gene-expression| atopic asthma| in-vitro	Mcmillan, SJ; Lloyd, CM	Prolonged allergen challenge in mice leads to persistent airway remodelling		CLINICAL AND EXPERIMENTAL ALLERGY	airway remodelling; allergic airway inflammation; asthma; eosinophils; Th2 cytokines	BRONCHIAL EPITHELIAL-CELLS; MOUSE ASTHMA MODEL; GROWTH-FACTOR-BETA; MURINE MODEL; SUBEPITHELIAL FIBROSIS; INTERFERON-GAMMA; TRANSFORMING GROWTH-FACTOR-BETA-1; GENE-EXPRESSION; ATOPIC ASTHMA; IN-VITRO	Background Inflammatory infiltrates, airway hyper-responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen-induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features. Objective The aim of this study was to use a murine model of prolonged allergen-induced airway inflammation in order to characterize the cells and molecules involved in the ensuing airway remodelling. Moreover, we investigated whether remodelling persists in the absence of continued allergen challenge. Methods Acute pulmonary eosinophilia and airways hyper-reactivity were induced after six serial allergen challenges in sensitized mice (acute phase). Mice were subsequently challenged three times a week with ovalbumin (OVA) (chronic phase) up to day 55. To investigate the persistence of pathology, one group of mice were left for another 4 weeks without further allergen challenge (day 80). Results The extended OVA challenge protocol caused significant airway remodelling, which was absent in the acute phase. Specifically, remodelling was characterized by deposition of collagen as well as airway smooth muscle and goblet cell hyperplasia. Importantly, these airway changes, together with tissue eosinophilia were sustained in the absence of further allergen challenge. Examination of cytokines revealed a dramatic up-regulation of IL-4 and tumour growth factor-beta1 during the chronic phase. Interestingly, while IL-4 levels were significantly increased during the chronic phase, levels of IL-13 fell. Levels of the Th1-associated cytokine IFN-gamma also increased during the chronic phase. Conclusion In conclusion, we have demonstrated that prolonged allergen challenge results in persistent airway wall remodelling.	49	140	2004	11	10.1111/j.1365-2222.2004.01895.x	Allergy; Immunology
Medication reconciliation: A practical tool to reduce the risk of medication errors. Preventable adverse drug events are associated with one out of five injuries or deaths. Estimates reveal that 46% of medication errors occur on admission or discharge from a clinical unit/hospital when patient orders are written. This study was performed to reduce medication errors in patient's discharge orders through a reconciliation process in an adult surgical intensive care unit (ICU). A discharge survey was implemented as part of the medication reconciliation process. The admitting nurse initiated the survey within 24 hours of ICU admission and the charge nurse completed the survey on discharge. Baseline data were obtained through a random sampling of 10% of discharges in first 2 weeks of the study (July 2001-May 2002). Medical and anesthesia records were reviewed, allergies and home medications verified with patient/family and findings compared with orders at time of ICU discharge. Baseline data revealed that 31 of 33 (94%) patients had orders changed. By week 24, nearly all medication errors in discharge orders were eliminated. In conclusion, use of the discharge survey in this medication reconciliation process resulted in a dramatic drop in medications errors for patients discharged from an ICU. The survey is now a part of our electronic medical record and used in 4 adult ICUs and 2 medicine floors. (C) 2003 Elsevier Inc. All rights reserved.. acute myocardial-infarction| hospitalized-patients| events| disease.	DEC-2003	acute myocardial-infarction| hospitalized-patients| events| disease	Pronovost, P; Weast, B; Schwarz, M; Wyskiel, RM; Prow, D; Milanovich, SN; Berenholtz, S; Dorman, T; Lipsett, P	Medication reconciliation: A practical tool to reduce the risk of medication errors		JOURNAL OF CRITICAL CARE		ACUTE MYOCARDIAL-INFARCTION; HOSPITALIZED-PATIENTS; EVENTS; DISEASE	Preventable adverse drug events are associated with one out of five injuries or deaths. Estimates reveal that 46% of medication errors occur on admission or discharge from a clinical unit/hospital when patient orders are written. This study was performed to reduce medication errors in patient's discharge orders through a reconciliation process in an adult surgical intensive care unit (ICU). A discharge survey was implemented as part of the medication reconciliation process. The admitting nurse initiated the survey within 24 hours of ICU admission and the charge nurse completed the survey on discharge. Baseline data were obtained through a random sampling of 10% of discharges in first 2 weeks of the study (July 2001-May 2002). Medical and anesthesia records were reviewed, allergies and home medications verified with patient/family and findings compared with orders at time of ICU discharge. Baseline data revealed that 31 of 33 (94%) patients had orders changed. By week 24, nearly all medication errors in discharge orders were eliminated. In conclusion, use of the discharge survey in this medication reconciliation process resulted in a dramatic drop in medications errors for patients discharged from an ICU. The survey is now a part of our electronic medical record and used in 4 adult ICUs and 2 medicine floors. (C) 2003 Elsevier Inc. All rights reserved.	17	140	2003	5	10.1016/S0883-9441(03)00108-4	General & Internal Medicine
Acute health effects of ambient air pollution: The ultrafine particle hypothesis. A strong and consistent association has been observed between adjusted mortality rates and ambient particle concentration. The strongest associations are seen for respiratory and cardiac deaths, particularly among the elderly. Particulate air pollution is also associated with asthma exacerbations, increased respiratory symptoms, decreased lung function, increased medication use, and increased hospital admissions. The U.S. Environmental Protection Agency (EPA) has recently promulgated a new national ambient air quality standard for fine particles, and yet the mechanisms for health effects at such low particle mass concentrations remain unclear. Hypotheses to identify the responsible particles have focused on particle acidity, particle content of transition metals, bioaerosols, and ultrafine particles. Because ultrafine particles are efficiently deposited in the respiratory tract and may be important in initiating airway inflammation, we have initiated clinical studies with ultrafine carbon particles in healthy subjects. These studies examine the role of ultrafines in: (1) the induction of airway inflammation; (2) expression of leukocyte and endothelial adhesion molecules in blood; (3) the alteration of blood coagulability; and (4) alteration in cardiac electrical activity. These events could lead to exacerbation of underlying cardiorespiratory disease. For example, airway inflammation may activate endothelium and circulating leukocytes, and induce a systemic acute phase response with transient hypercoagulability; this could explain the epidemiologic linkages between pollutant exposures and cardiovascular events. These approaches should be useful in identifying mechanisms for pollutant-induced respiratory and systemic effects, and in providing data for determining appropriate air quality standards.. air pollution| particulate matter| ultrafine particles|mortality.	WIN-2000	air pollution| particulate matter| ultrafine particles|mortality	Utell, MJ; Frampton, MW	Acute health effects of ambient air pollution: The ultrafine particle hypothesis		JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG	air pollution; particulate matter; ultrafine particles	MORTALITY	A strong and consistent association has been observed between adjusted mortality rates and ambient particle concentration. The strongest associations are seen for respiratory and cardiac deaths, particularly among the elderly. Particulate air pollution is also associated with asthma exacerbations, increased respiratory symptoms, decreased lung function, increased medication use, and increased hospital admissions. The U.S. Environmental Protection Agency (EPA) has recently promulgated a new national ambient air quality standard for fine particles, and yet the mechanisms for health effects at such low particle mass concentrations remain unclear. Hypotheses to identify the responsible particles have focused on particle acidity, particle content of transition metals, bioaerosols, and ultrafine particles. Because ultrafine particles are efficiently deposited in the respiratory tract and may be important in initiating airway inflammation, we have initiated clinical studies with ultrafine carbon particles in healthy subjects. These studies examine the role of ultrafines in: (1) the induction of airway inflammation; (2) expression of leukocyte and endothelial adhesion molecules in blood; (3) the alteration of blood coagulability; and (4) alteration in cardiac electrical activity. These events could lead to exacerbation of underlying cardiorespiratory disease. For example, airway inflammation may activate endothelium and circulating leukocytes, and induce a systemic acute phase response with transient hypercoagulability; this could explain the epidemiologic linkages between pollutant exposures and cardiovascular events. These approaches should be useful in identifying mechanisms for pollutant-induced respiratory and systemic effects, and in providing data for determining appropriate air quality standards.	22	140	2000	5	10.1089/jam.2000.13.355	Public, Environmental & Occupational Health; Respiratory System
Safety of a peanut oral immunotherapy protocol in children with peanut allergy. Background: Oral immunotherapy (OIT) offers a promising therapeutic option for peanut allergy. Given that during OIT an allergic patient ingests an allergen that could potentially cause a serious reaction, the safety of OIT is of particular concern. Objective: The purpose of this study was to examine safety during the initial escalation day, buildup phase, and home dosing phase in subjects enrolled in a peanut OIT study. Methods: Skin, upper respiratory tract, chest, and abdominal symptoms were recorded with initial escalation day and buildup phase dosings. Subjects also maintained daily diaries detailing symptoms after each home dosing. A statistical analysis of these data was performed. Results: Twenty of 28 patients completed all phases of the study. During the initial escalation day, upper respiratory tract (79%) and abdominal (68%) symptoms were the most likely symptoms experienced. The risk of mild wheezing during the initial escalation day was 18%. The probability of having any symptoms after a buildup phase dose was 46%, with a risk of 29% for upper respiratory tract symptoms and 24% for skin symptoms. The risk of reaction with any home dose was 3.5%. Upper respiratory tract (1.2%) and skin (1.1%) symptoms were the most likely after home doses. Treatment was given with 0.7% of home doses. Two subjects received epinephrine after I home dose each. Conclusions: Subjects were more likely to have significant allergic symptoms during the initial escalation day when they were in a closely monitored setting than during other phases of the study. Allergic reactions with home doses were rare. (J Allergy Clin Immunol 2009;124:286-91.). peanut| food allergy| oral immunotherapy|tree nut allergy| anaphylactic reactions| tolerance induction| egg allergy| food| desensitization.	AUG-2009	peanut| food allergy| oral immunotherapy|tree nut allergy| anaphylactic reactions| tolerance induction| egg allergy| food| desensitization	Hofmann, AM; Scurlock, AM; Jones, SM; Palmer, KP; Lokhnygina, Y; Steele, PH; Kamilaris, J; Burks, AW	Safety of a peanut oral immunotherapy protocol in children with peanut allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Peanut; food allergy; oral immunotherapy	TREE NUT ALLERGY; ANAPHYLACTIC REACTIONS; TOLERANCE INDUCTION; EGG ALLERGY; FOOD; DESENSITIZATION	Background: Oral immunotherapy (OIT) offers a promising therapeutic option for peanut allergy. Given that during OIT an allergic patient ingests an allergen that could potentially cause a serious reaction, the safety of OIT is of particular concern. Objective: The purpose of this study was to examine safety during the initial escalation day, buildup phase, and home dosing phase in subjects enrolled in a peanut OIT study. Methods: Skin, upper respiratory tract, chest, and abdominal symptoms were recorded with initial escalation day and buildup phase dosings. Subjects also maintained daily diaries detailing symptoms after each home dosing. A statistical analysis of these data was performed. Results: Twenty of 28 patients completed all phases of the study. During the initial escalation day, upper respiratory tract (79%) and abdominal (68%) symptoms were the most likely symptoms experienced. The risk of mild wheezing during the initial escalation day was 18%. The probability of having any symptoms after a buildup phase dose was 46%, with a risk of 29% for upper respiratory tract symptoms and 24% for skin symptoms. The risk of reaction with any home dose was 3.5%. Upper respiratory tract (1.2%) and skin (1.1%) symptoms were the most likely after home doses. Treatment was given with 0.7% of home doses. Two subjects received epinephrine after I home dose each. Conclusions: Subjects were more likely to have significant allergic symptoms during the initial escalation day when they were in a closely monitored setting than during other phases of the study. Allergic reactions with home doses were rare. (J Allergy Clin Immunol 2009;124:286-91.)	21	139	2009	6	10.1016/j.jaci.2009.03.045	Allergy; Immunology
South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia phylicoides-A review. Rooibos (Aspalathus linearis (Brum.f) Dahlg.) and honeybush (Cyclopia Vent. species) are popular indigenous South African herbal teas enjoyed for their taste and aroma. Traditional medicinal uses of rooibos in South Africa include alleviation of infantile colic, allergies, asthma and dermatological problems, while a decoction of honeybush was used as a restorative and as an expectorant in chronic catarrh and pulmonary tuberculosis. Traditional medicinal uses of Athrixia phylicoides DC., or bush tea, another indigenous South African plant with very limited localised use as herbal tea, include treatment of boils, acne, infected wounds and infected throats. Currently rooibos and honeybush are produced for the herbal tea market, while bush tea has potential for commercialisation. A summary of the historical and modern uses, botany, distribution, industry and chemical composition of these herbal teas is presented. A comprehensive discussion of in vitro, ex vivo and in vivo biological properties, required to expand their applications as nutraceutical and cosmeceutical products, is included, with the main emphasis on rooibos. Future research needs include more comprehensive chemical characterisation of extracts, identification of marker compounds for extract standardisation and quality control, bioavailability and identification of bio-markers of dietary exposure, investigation of possible herb-drug interactions and plant improvement with regards to composition and bioactivity. (C) 2008 Elsevier Ireland Ltd. All rights reserved.. anticarcinogenic| antioxidant| bush tea| chemical composition| honeybush| phyto-oestrogenic| polyphenols| rooibos|camellia-sinensis teas| antioxidant activity relationships| batch extraction conditions| major phenolic-compounds| fixed-bed extraction| rooibos tea| honeybush tea| aqueous extracts| bush tea| in-vitro.	OCT 28-2008	anticarcinogenic| antioxidant| bush tea| chemical composition| honeybush| phyto-oestrogenic| polyphenols| rooibos|camellia-sinensis teas| antioxidant activity relationships| batch extraction conditions| major phenolic-compounds| fixed-bed extraction| rooibos tea| honeybush tea| aqueous extracts| bush tea| in-vitro	Joubert, E; Gelderblom, WCA; Louw, A; de Beer, D	South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia phylicoides-A review		JOURNAL OF ETHNOPHARMACOLOGY	Anticarcinogenic; Antioxidant; Bush tea; Chemical composition; Honeybush; Phyto-oestrogenic; Polyphenols; Rooibos	CAMELLIA-SINENSIS TEAS; ANTIOXIDANT ACTIVITY RELATIONSHIPS; BATCH EXTRACTION CONDITIONS; MAJOR PHENOLIC-COMPOUNDS; FIXED-BED EXTRACTION; ROOIBOS TEA; HONEYBUSH TEA; AQUEOUS EXTRACTS; BUSH TEA; IN-VITRO	Rooibos (Aspalathus linearis (Brum.f) Dahlg.) and honeybush (Cyclopia Vent. species) are popular indigenous South African herbal teas enjoyed for their taste and aroma. Traditional medicinal uses of rooibos in South Africa include alleviation of infantile colic, allergies, asthma and dermatological problems, while a decoction of honeybush was used as a restorative and as an expectorant in chronic catarrh and pulmonary tuberculosis. Traditional medicinal uses of Athrixia phylicoides DC., or bush tea, another indigenous South African plant with very limited localised use as herbal tea, include treatment of boils, acne, infected wounds and infected throats. Currently rooibos and honeybush are produced for the herbal tea market, while bush tea has potential for commercialisation. A summary of the historical and modern uses, botany, distribution, industry and chemical composition of these herbal teas is presented. A comprehensive discussion of in vitro, ex vivo and in vivo biological properties, required to expand their applications as nutraceutical and cosmeceutical products, is included, with the main emphasis on rooibos. Future research needs include more comprehensive chemical characterisation of extracts, identification of marker compounds for extract standardisation and quality control, bioavailability and identification of bio-markers of dietary exposure, investigation of possible herb-drug interactions and plant improvement with regards to composition and bioactivity. (C) 2008 Elsevier Ireland Ltd. All rights reserved.	211	139	2008	37	10.1016/j.jep.2008.06.014	Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine
The association between phthalates in dust and allergic diseases among Bulgarian children. BACKGROUND: Recent studies have identified associations between the concentration of phthalates in indoor dust and allergic symptoms in the airways, nose, and skin. OBJECTIVES: Our goal was to investigate the associations between allergic symptoms in children and the concentration of phthalate esters in settled dust collected from children's homes in Sofia and Burgas, Bulgaria. METHODS: Dust samples from the child's bedroom were collected. A total of 102 children (2-7 Years of age) had symptoms of wheezing, rhinitis, and/or eczema in preceding 12 months (cases), and 82 were nonsymptomatic (controls). The dust samples were analyzed for their content of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP). RESULTS: A higher concentration of DEHP was found in homes of case children than in those of controls (1.24 vs. 0.86 mg/g dust). The concentration of DEHP was significantly associated with wheezing in the preceding 12 months (p = 0.035) as reported by parents. We found a dose-response relationship between DEHP concentration and case status and between DEHP concentration and wheezing in the preceding 12 months. CONCLUSIONS: This study shows an association between concentration of DEHP in indoor dust and wheezing among preschool children in Bulgaria.. allergy| asthma| children| dehp| phthalates|in-house dust| interior surface materials| di(2-ethylhexyl) phthalate| preschool-children| young-children| indoor air| asthma| symptoms| exposure| population.	JAN-2008	allergy| asthma| children| dehp| phthalates|in-house dust| interior surface materials| di(2-ethylhexyl) phthalate| preschool-children| young-children| indoor air| asthma| symptoms| exposure| population	Kolarik, B; Naydenov, K; Larsson, M; Bornehag, CG; Sundell, J	The association between phthalates in dust and allergic diseases among Bulgarian children		ENVIRONMENTAL HEALTH PERSPECTIVES	allergy; asthma; children; DEHP; phthalates	IN-HOUSE DUST; INTERIOR SURFACE MATERIALS; DI(2-ETHYLHEXYL) PHTHALATE; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; INDOOR AIR; ASTHMA; SYMPTOMS; EXPOSURE; POPULATION	BACKGROUND: Recent studies have identified associations between the concentration of phthalates in indoor dust and allergic symptoms in the airways, nose, and skin. OBJECTIVES: Our goal was to investigate the associations between allergic symptoms in children and the concentration of phthalate esters in settled dust collected from children's homes in Sofia and Burgas, Bulgaria. METHODS: Dust samples from the child's bedroom were collected. A total of 102 children (2-7 Years of age) had symptoms of wheezing, rhinitis, and/or eczema in preceding 12 months (cases), and 82 were nonsymptomatic (controls). The dust samples were analyzed for their content of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), and di-n-octyl phthalate (DnOP). RESULTS: A higher concentration of DEHP was found in homes of case children than in those of controls (1.24 vs. 0.86 mg/g dust). The concentration of DEHP was significantly associated with wheezing in the preceding 12 months (p = 0.035) as reported by parents. We found a dose-response relationship between DEHP concentration and case status and between DEHP concentration and wheezing in the preceding 12 months. CONCLUSIONS: This study shows an association between concentration of DEHP in indoor dust and wheezing among preschool children in Bulgaria.	36	139	2008	6	10.1289/ehp.10498	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Near-highway pollutants in motor vehicle exhaust: A review of epidemiologic evidence of cardiac and pulmonary health risks. There is growing evidence of a distinct set of freshly-emitted air pollutants downwind from major highways, motorways, and freeways that include elevated levels of ultrafine particulates (UFP), black carbon (BC), oxides of nitrogen (NOx), and carbon monoxide (CO). People living or otherwise spending substantial time within about 200 m of highways are exposed to these pollutants more so than persons living at a greater distance, even compared to living on busy urban streets. Evidence of the health hazards of these pollutants arises from studies that assess proximity to highways, actual exposure to the pollutants, or both. Taken as a whole, the health studies show elevated risk for development of asthma and reduced lung function in children who live near major highways. Studies of particulate matter (PM) that show associations with cardiac and pulmonary mortality also appear to indicate increasing risk as smaller geographic areas are studied, suggesting localized sources that likely include major highways. Although less work has tested the association between lung cancer and highways, the existing studies suggest an association as well. While the evidence is substantial for a link between near-highway exposures and adverse health outcomes, considerable work remains to understand the exact nature and magnitude of the risks.. particulate air-pollution| heart-rate-variability| long-term exposure| chronic respiratory symptoms| lung-cancer| ultrafine particles| submicrometer particles| childhood asthma| school-children| urban air.	AUG 9-2007	particulate air-pollution| heart-rate-variability| long-term exposure| chronic respiratory symptoms| lung-cancer| ultrafine particles| submicrometer particles| childhood asthma| school-children| urban air	Brugge, D; Durant, JL; Rioux, C	Near-highway pollutants in motor vehicle exhaust: A review of epidemiologic evidence of cardiac and pulmonary health risks		ENVIRONMENTAL HEALTH		PARTICULATE AIR-POLLUTION; HEART-RATE-VARIABILITY; LONG-TERM EXPOSURE; CHRONIC RESPIRATORY SYMPTOMS; LUNG-CANCER; ULTRAFINE PARTICLES; SUBMICROMETER PARTICLES; CHILDHOOD ASTHMA; SCHOOL-CHILDREN; URBAN AIR	There is growing evidence of a distinct set of freshly-emitted air pollutants downwind from major highways, motorways, and freeways that include elevated levels of ultrafine particulates (UFP), black carbon (BC), oxides of nitrogen (NOx), and carbon monoxide (CO). People living or otherwise spending substantial time within about 200 m of highways are exposed to these pollutants more so than persons living at a greater distance, even compared to living on busy urban streets. Evidence of the health hazards of these pollutants arises from studies that assess proximity to highways, actual exposure to the pollutants, or both. Taken as a whole, the health studies show elevated risk for development of asthma and reduced lung function in children who live near major highways. Studies of particulate matter (PM) that show associations with cardiac and pulmonary mortality also appear to indicate increasing risk as smaller geographic areas are studied, suggesting localized sources that likely include major highways. Although less work has tested the association between lung cancer and highways, the existing studies suggest an association as well. While the evidence is substantial for a link between near-highway exposures and adverse health outcomes, considerable work remains to understand the exact nature and magnitude of the risks.	91	139	2007	12	10.1186/1476-069X-6-23	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Synergistic effects of traffic-related air pollution and exposure to violence on urban asthma etiology. BACKGROUND: Disproportionate-life stress and consequent physiologic alteration (i.e., immune dysregulation) has been proposed as a major pathway linking socioeconomic position, environmental exposures, and health disparities. Asthma, for example, disproportionately affects lower-income urban communities, where air pollution and social stressors may be elevated. OBJECTIVES: We aimed to examine the role of exposure to violence (ETV), as a chronic stressor, in altering susceptibility to traffic-related air pollution in asthma etiology. METHODS: We developed geographic information systems (GIS)-based models to retrospectively estimate residential exposures to traffic-related pollution for 413 children in a community-based pregnancy cohort, recruited in East Boston, Massachusetts, between 1987 and 1993, using monthly nitrogen dioxide measurements for 13 sites over 18 years. We merged pollution estimates with questionnaire data on lifetime ETV and examined the effects of both on childhood asthma etiology. RESULTS: Correcting for potential confounders, we found an elevated risk of asthma with a 1-SD (4.3 ppb) increase in NO2 exposure solely among children with above-median ETV [odds ratio (OR) = 1.63; 95% confidence interval (0), 1.14-2-33)]. Among children always living in the same community, with lesser exposure measurement error, this association was magnified (OR = 2.40; 95% Cl, 1.48-3.88). Of multiple exposure periods, year-of-diagnosis NO2 was most predictive of asthma, outcomes. CONCLUSIONS: We found an association between traffic-related air pollution and asthma solely among urban children exposed to violence. Future studies should consider socially patterned susceptibility, common spatial distributions of social and physical environmental factors, and potential synergies among these. Prospective assessment of physical and social exposures may help determine causal pathways and critical exposure periods.. childhood asthma| exposure to violence (etv)| geographic information systems (gis)| intraurban variability| nitrogen dioxide (no2)| social-environmental synergy| stress|community violence| environmental justice| health disparities| stress reactivity| childhood asthma| lung-function| birth-cohort| children| association| symptoms.	AUG-2007	childhood asthma| exposure to violence (etv)| geographic information systems (gis)| intraurban variability| nitrogen dioxide (no2)| social-environmental synergy| stress|community violence| environmental justice| health disparities| stress reactivity| childhood asthma| lung-function| birth-cohort| children| association| symptoms	Clougherty, JE; Levy, JI; Kubzansky, LD; Ryan, PB; Suglia, SF; Canner, MJ; Wright, RJ	Synergistic effects of traffic-related air pollution and exposure to violence on urban asthma etiology		ENVIRONMENTAL HEALTH PERSPECTIVES	childhood asthma; exposure to violence (ETV); geographic information systems (GIS); intraurban variability; nitrogen dioxide (NO2); social-environmental synergy; stress	COMMUNITY VIOLENCE; ENVIRONMENTAL JUSTICE; HEALTH DISPARITIES; STRESS REACTIVITY; CHILDHOOD ASTHMA; LUNG-FUNCTION; BIRTH-COHORT; CHILDREN; ASSOCIATION; SYMPTOMS	BACKGROUND: Disproportionate-life stress and consequent physiologic alteration (i.e., immune dysregulation) has been proposed as a major pathway linking socioeconomic position, environmental exposures, and health disparities. Asthma, for example, disproportionately affects lower-income urban communities, where air pollution and social stressors may be elevated. OBJECTIVES: We aimed to examine the role of exposure to violence (ETV), as a chronic stressor, in altering susceptibility to traffic-related air pollution in asthma etiology. METHODS: We developed geographic information systems (GIS)-based models to retrospectively estimate residential exposures to traffic-related pollution for 413 children in a community-based pregnancy cohort, recruited in East Boston, Massachusetts, between 1987 and 1993, using monthly nitrogen dioxide measurements for 13 sites over 18 years. We merged pollution estimates with questionnaire data on lifetime ETV and examined the effects of both on childhood asthma etiology. RESULTS: Correcting for potential confounders, we found an elevated risk of asthma with a 1-SD (4.3 ppb) increase in NO2 exposure solely among children with above-median ETV [odds ratio (OR) = 1.63; 95% confidence interval (0), 1.14-2-33)]. Among children always living in the same community, with lesser exposure measurement error, this association was magnified (OR = 2.40; 95% Cl, 1.48-3.88). Of multiple exposure periods, year-of-diagnosis NO2 was most predictive of asthma, outcomes. CONCLUSIONS: We found an association between traffic-related air pollution and asthma solely among urban children exposed to violence. Future studies should consider socially patterned susceptibility, common spatial distributions of social and physical environmental factors, and potential synergies among these. Prospective assessment of physical and social exposures may help determine causal pathways and critical exposure periods.	57	139	2007	7	10.1289/ehp.9863	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Air pollution and allergy: you are what you breathe. How does air pollution affect asthma and allergic rhinitis? Particulate and gaseous pollution drive proallergic inflammation through the generation of oxidative stress, which is regulated by individual genetic susceptibility.. s-transferase m1| ozone exposure| polymorphisms| challenge| responses| children| asthma| cells.	MAR-2005	s-transferase m1| ozone exposure| polymorphisms| challenge| responses| children| asthma| cells	Saxon, A; Diaz-Sanchez, D	Air pollution and allergy: you are what you breathe		NATURE IMMUNOLOGY		S-TRANSFERASE M1; OZONE EXPOSURE; POLYMORPHISMS; CHALLENGE; RESPONSES; CHILDREN; ASTHMA; CELLS	How does air pollution affect asthma and allergic rhinitis? Particulate and gaseous pollution drive proallergic inflammation through the generation of oxidative stress, which is regulated by individual genetic susceptibility.	20	139	2005	4	10.1038/ni0305-223	Immunology
Early life risk factors for current wheeze, asthma, and bronchial hyperresponsiveness at 10 years of age. Study objectives: We sought to identify early life factors (ie, first 4 years) associated with wheeze, asthma, and bronchial hyperresponsiveness (BHR) at age 10 years, comparing their relative influence for these conditions. Methods: Children were seen at birth, and at 1, 2, 4, and 10 years of age in a whole-population birth cohort study (1,456 subjects). Information was collected prospectively on genetic and environmental risk factors. Skin-prick testing was performed at 4 years of age. Current wheeze (in the last 12 months) and currently diagnosed asthma (CDA) [ie, current wheeze and ever-diagnosed asthmatic subject] were recorded at 10 years of age when BHR was measured at bronchial challenge. Independent significant risk factors for these outcomes were identified by logistic regression. Results: Independent significance for current wheeze occurred with maternal asthma (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.27 to 3.41) and paternal asthma (OR,. 2.12; 95% CI 1.29 to 3.51), recurrent chest infections at 2 years (OR, 3.98; 95% CI, 2.36 to 6.70), atopy at 4 years of age (OR, 3.69; 95% CI, 2.36 to 5.76), eczema at 4 years of age (OR, 2.15; 95% CI, 1.24 to 3.73), and parental smoking at 4 years of age (OR, 2.18; 95% CI, 1.25 to 3.81). For CDA, significant factors were maternal asthma (OR, 2.26; 95% CI, 1.24 to 3.73), paternal asthma (OR, 2.30; 95% CI, 1.17 to 4.52), and sibling asthma (OR, 2.00; 95% CI, 1.16 to 3.43), recurrent chest infections at I year of age (OR, 2.67; 95% CI, 1.12 to 6.40) and 2 years of age (OR, 4.11; 95% CI, 2.06 to S. IS), atopy at 4 years of age (OR, 7.22; 95% CI, 4.13 to 12.62), parental smoking at I year of age (OR, 1.99; 95% CI, 1.15 to 3.45), and male gender (OR, 1.72; 95% CI, 1.01 to 2.95). For BHR, atopy at 4 years of age (OR, 5.38; 95% CI, 3.06 to 9.47) and high social class at birth (OR, 2.03; 95% CI, 1.16 to 3.53) proved to be significant. Conclusions: Asthmatic heredity, predisposition to early life atopy, plus early passive smoke exposure and recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age. BHR at 10 years of age has a narrower risk profile, suggesting that factors influencing wheezing symptom expression may differ from those predisposing the patient to BHR.. atopy| bronchial hyperresponsiveness| childhood asthma| risk factors| wheezing|australian schoolchildren| environmental-factors| respiratory symptoms| allergic disorders| parental smoking| 2 populations| birth cohort| new-zealand| children| prevalence.	FEB-2005	atopy| bronchial hyperresponsiveness| childhood asthma| risk factors| wheezing|australian schoolchildren| environmental-factors| respiratory symptoms| allergic disorders| parental smoking| 2 populations| birth cohort| new-zealand| children| prevalence	Arshad, SH; Kurukulaaratchy, RJ; Fenn, M; Matthews, S	Early life risk factors for current wheeze, asthma, and bronchial hyperresponsiveness at 10 years of age		CHEST	atopy; bronchial hyperresponsiveness; childhood asthma; risk factors; wheezing	AUSTRALIAN SCHOOLCHILDREN; ENVIRONMENTAL-FACTORS; RESPIRATORY SYMPTOMS; ALLERGIC DISORDERS; PARENTAL SMOKING; 2 POPULATIONS; BIRTH COHORT; NEW-ZEALAND; CHILDREN; PREVALENCE	Study objectives: We sought to identify early life factors (ie, first 4 years) associated with wheeze, asthma, and bronchial hyperresponsiveness (BHR) at age 10 years, comparing their relative influence for these conditions. Methods: Children were seen at birth, and at 1, 2, 4, and 10 years of age in a whole-population birth cohort study (1,456 subjects). Information was collected prospectively on genetic and environmental risk factors. Skin-prick testing was performed at 4 years of age. Current wheeze (in the last 12 months) and currently diagnosed asthma (CDA) [ie, current wheeze and ever-diagnosed asthmatic subject] were recorded at 10 years of age when BHR was measured at bronchial challenge. Independent significant risk factors for these outcomes were identified by logistic regression. Results: Independent significance for current wheeze occurred with maternal asthma (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.27 to 3.41) and paternal asthma (OR,. 2.12; 95% CI 1.29 to 3.51), recurrent chest infections at 2 years (OR, 3.98; 95% CI, 2.36 to 6.70), atopy at 4 years of age (OR, 3.69; 95% CI, 2.36 to 5.76), eczema at 4 years of age (OR, 2.15; 95% CI, 1.24 to 3.73), and parental smoking at 4 years of age (OR, 2.18; 95% CI, 1.25 to 3.81). For CDA, significant factors were maternal asthma (OR, 2.26; 95% CI, 1.24 to 3.73), paternal asthma (OR, 2.30; 95% CI, 1.17 to 4.52), and sibling asthma (OR, 2.00; 95% CI, 1.16 to 3.43), recurrent chest infections at I year of age (OR, 2.67; 95% CI, 1.12 to 6.40) and 2 years of age (OR, 4.11; 95% CI, 2.06 to S. IS), atopy at 4 years of age (OR, 7.22; 95% CI, 4.13 to 12.62), parental smoking at I year of age (OR, 1.99; 95% CI, 1.15 to 3.45), and male gender (OR, 1.72; 95% CI, 1.01 to 2.95). For BHR, atopy at 4 years of age (OR, 5.38; 95% CI, 3.06 to 9.47) and high social class at birth (OR, 2.03; 95% CI, 1.16 to 3.53) proved to be significant. Conclusions: Asthmatic heredity, predisposition to early life atopy, plus early passive smoke exposure and recurrent chest infections are important influences for the occurrence of wheeze and asthma at 10 years of age. BHR at 10 years of age has a narrower risk profile, suggesting that factors influencing wheezing symptom expression may differ from those predisposing the patient to BHR.	39	139	2005	7	10.1378/chest.127.2.502	General & Internal Medicine; Respiratory System
The impact of community design and land-use choices on public health: A scientific research agenda. The design of a community's built environment influences the physical and mental health of its residents. Because few studies have investigated this relationship, the Centers for Disease Control and Prevention hosted a workshop in May 2002 to help develop a scientific research agenda on these issues. Workshop participants' areas of expertise included physical activity, injury prevention, air pollution, water quality, urban planning, transportation, architecture, epidemiology, land use, mental health, social capital, housing, and social marketing. This report describes the 37 questions in the resulting research agenda. The next steps are to define priorities and obtain resources. The proposed research will help identify the best practices for designing new communities and revitalizing old ones in ways that promote physical and mental health.. outdoor air-pollution| physical-activity| built environment| children| trends| sprawl| asthma.	SEP-2003	outdoor air-pollution| physical-activity| built environment| children| trends| sprawl| asthma	Dannenberg, AL; Jackson, RJ; Frumkin, H; Schieber, RA; Pratt, M; Kochtitzky, C; Tilson, HH	The impact of community design and land-use choices on public health: A scientific research agenda		AMERICAN JOURNAL OF PUBLIC HEALTH		OUTDOOR AIR-POLLUTION; PHYSICAL-ACTIVITY; BUILT ENVIRONMENT; CHILDREN; TRENDS; SPRAWL; ASTHMA	The design of a community's built environment influences the physical and mental health of its residents. Because few studies have investigated this relationship, the Centers for Disease Control and Prevention hosted a workshop in May 2002 to help develop a scientific research agenda on these issues. Workshop participants' areas of expertise included physical activity, injury prevention, air pollution, water quality, urban planning, transportation, architecture, epidemiology, land use, mental health, social capital, housing, and social marketing. This report describes the 37 questions in the resulting research agenda. The next steps are to define priorities and obtain resources. The proposed research will help identify the best practices for designing new communities and revitalizing old ones in ways that promote physical and mental health.	56	139	2003	9	10.2105/AJPH.93.9.1500	Public, Environmental & Occupational Health
Is allergen exposure the major primary cause of asthma?. In recent decades a number of authors have argued that allergen exposure is the major primary cause of asthma, and that the global increases in asthma prevalence are due to increases in exposure to aeroallergens. We have assessed the epidemiological evidence in support of this hypothesis. No longitudinal studies were identified in which allergen exposure during infancy in a random population sample has been related to asthma risk after the age of six years. Two studies have been conducted in selected populations chosen on the basis of a family history of asthma or allergy; one study found a nonstatistically significant association whereas the other study found no association. Many of the identified prevalence studies in children showed negative associations between allergen exposure and current asthma, and the weighted averages of the population attributable risks in children were 4% for Der p 1, 11% for Fel d 1, -4% for Bla g 2, and 6% for Can f 1. There was little change in these estimates in studies in which children whose parents had adopted allergen avoidance measures were excluded. Furthermore, evidence from population studies is equivocal and provides little consistent evidence that allergen exposure is associated with the prevalence of asthma at the population level. Population-based cohort studies are clearly required, but currently available evidence does not indicate that allergen exposure is a major risk factor for the primary causation of asthma in children.. asthma| allergen| childhood exposure| atopy|dust mite allergen| papua-new-guinea| inner-city children| der-p-i| respiratory symptoms| childhood asthma| risk-factors| los-alamos| new-mexico| prevalence.	MAY-2000	asthma| allergen| childhood exposure| atopy|dust mite allergen| papua-new-guinea| inner-city children| der-p-i| respiratory symptoms| childhood asthma| risk-factors| los-alamos| new-mexico| prevalence	Pearce, N; Douwes, J; Beasley, R	Is allergen exposure the major primary cause of asthma?		THORAX	asthma; allergen; childhood exposure; atopy	DUST MITE ALLERGEN; PAPUA-NEW-GUINEA; INNER-CITY CHILDREN; DER-P-I; RESPIRATORY SYMPTOMS; CHILDHOOD ASTHMA; RISK-FACTORS; LOS-ALAMOS; NEW-MEXICO; PREVALENCE	In recent decades a number of authors have argued that allergen exposure is the major primary cause of asthma, and that the global increases in asthma prevalence are due to increases in exposure to aeroallergens. We have assessed the epidemiological evidence in support of this hypothesis. No longitudinal studies were identified in which allergen exposure during infancy in a random population sample has been related to asthma risk after the age of six years. Two studies have been conducted in selected populations chosen on the basis of a family history of asthma or allergy; one study found a nonstatistically significant association whereas the other study found no association. Many of the identified prevalence studies in children showed negative associations between allergen exposure and current asthma, and the weighted averages of the population attributable risks in children were 4% for Der p 1, 11% for Fel d 1, -4% for Bla g 2, and 6% for Can f 1. There was little change in these estimates in studies in which children whose parents had adopted allergen avoidance measures were excluded. Furthermore, evidence from population studies is equivocal and provides little consistent evidence that allergen exposure is associated with the prevalence of asthma at the population level. Population-based cohort studies are clearly required, but currently available evidence does not indicate that allergen exposure is a major risk factor for the primary causation of asthma in children.	50	139	2000	8	10.1136/thorax.55.5.424	Respiratory System
The function of Fc gamma receptors in dendritic cells and macrophages. Dendritic cells (DCs) and macrophages use various receptors to recognize foreign antigens and to receive feedback control from adaptive immune cells. Although it was long believed that all immunoglobutin Fc receptors are universally expressed by phagocytes, recent findings indicate that only monocyte-derived DCs and macrophages express high levels of activating Fc receptors for IgG (Fc gamma Rs), whereas conventional and plasmacytoid DCs express the inhibitory Fc gamma R. In this Review, we discuss how the uptake, processing and presentation of antigens by DCs and macrophages is influenced by Fc gamma R recognition of innmunoglobulins and immune complexes in the steady state and during inflammation.. cytoplasmic domain heterogeneity| antibody-dependent enhancement| dengue hemorrhagic-fever| igg immune-complexes| rii-mediated uptake| dust mite allergen| cd8(+) t-cells| antigen presentation| in-vivo| cross-presentation.	FEB-2014	cytoplasmic domain heterogeneity| antibody-dependent enhancement| dengue hemorrhagic-fever| igg immune-complexes| rii-mediated uptake| dust mite allergen| cd8(+) t-cells| antigen presentation| in-vivo| cross-presentation	Guilliams, M; Bruhns, P; Saeys, Y; Hammad, H; Lambrecht, BN	The function of Fc gamma receptors in dendritic cells and macrophages		NATURE REVIEWS IMMUNOLOGY		CYTOPLASMIC DOMAIN HETEROGENEITY; ANTIBODY-DEPENDENT ENHANCEMENT; DENGUE HEMORRHAGIC-FEVER; IGG IMMUNE-COMPLEXES; RII-MEDIATED UPTAKE; DUST MITE ALLERGEN; CD8(+) T-CELLS; ANTIGEN PRESENTATION; IN-VIVO; CROSS-PRESENTATION	Dendritic cells (DCs) and macrophages use various receptors to recognize foreign antigens and to receive feedback control from adaptive immune cells. Although it was long believed that all immunoglobutin Fc receptors are universally expressed by phagocytes, recent findings indicate that only monocyte-derived DCs and macrophages express high levels of activating Fc receptors for IgG (Fc gamma Rs), whereas conventional and plasmacytoid DCs express the inhibitory Fc gamma R. In this Review, we discuss how the uptake, processing and presentation of antigens by DCs and macrophages is influenced by Fc gamma R recognition of innmunoglobulins and immune complexes in the steady state and during inflammation.	152	138	2014	15	10.1038/nri3582	Immunology
Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset Asthma. BACKGROUND Both genetic variation at the 17q21 locus and virus-induced respiratory wheezing illnesses are associated with the development of asthma. Our aim was to determine the effects of these two factors on the risk of asthma in the Childhood Origins of Asthma (COAST) and the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohorts. METHODS We tested genotypes at the 17q21 locus for associations with asthma and with human rhinovirus (HRV) and respiratory syncytial virus (RSV) wheezing illnesses and tested for interactions between 17q21 genotypes and HRV and RSV wheezing illnesses with respect to the risk of asthma. Finally, we examined genotype-specific expression of 17q21 genes in unstimulated and HRV-stimulated peripheral-blood mononuclear cells (PBMCs). RESULTS The 17q21 variants were associated with HRV wheezing illnesses in early life, but not with RSV wheezing illnesses. The associations of 17q21 variants with asthma were restricted to children who had had HRV wheezing illnesses, resulting in a significant interaction effect with respect to the risk of asthma. Moreover, the expression levels of ORMDL3 and of GSDMB were significantly increased in HRV-stimulated PBMCs, as compared with unstimulated PBMCs. The expression of these genes was associated with 17q21 variants in both conditions, although the increase with exposure to HRV was not genotype-specific. CONCLUSIONS Variants at the 17q21 locus were associated with asthma in children who had had HRV wheezing illnesses and with expression of two genes at this locus. The expression levels of both genes increased in response to HRV stimulation, although the relative increase was not associated with the 17q21 genotypes. (Funded by the National Institutes of Health.). gasdermin-like gsdml| 17q21 variants| smoke exposure| expression| ormdl3| association| exacerbations| infections| children| disease.	APR 11-2013	gasdermin-like gsdml| 17q21 variants| smoke exposure| expression| ormdl3| association| exacerbations| infections| children| disease	Caliskan, M; Bochkov, YA; Kreiner-Moller, E; Bonnelykke, K; Stein, MM; Du, GX; Bisgaard, H; Jackson, DJ; Gern, JE; Lemanske, RF; Nicolae, DL; Ober, C	Rhinovirus Wheezing Illness and Genetic Risk of Childhood-Onset Asthma		NEW ENGLAND JOURNAL OF MEDICINE		GASDERMIN-LIKE GSDML; 17Q21 VARIANTS; SMOKE EXPOSURE; EXPRESSION; ORMDL3; ASSOCIATION; EXACERBATIONS; INFECTIONS; CHILDREN; DISEASE	BACKGROUND Both genetic variation at the 17q21 locus and virus-induced respiratory wheezing illnesses are associated with the development of asthma. Our aim was to determine the effects of these two factors on the risk of asthma in the Childhood Origins of Asthma (COAST) and the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohorts. METHODS We tested genotypes at the 17q21 locus for associations with asthma and with human rhinovirus (HRV) and respiratory syncytial virus (RSV) wheezing illnesses and tested for interactions between 17q21 genotypes and HRV and RSV wheezing illnesses with respect to the risk of asthma. Finally, we examined genotype-specific expression of 17q21 genes in unstimulated and HRV-stimulated peripheral-blood mononuclear cells (PBMCs). RESULTS The 17q21 variants were associated with HRV wheezing illnesses in early life, but not with RSV wheezing illnesses. The associations of 17q21 variants with asthma were restricted to children who had had HRV wheezing illnesses, resulting in a significant interaction effect with respect to the risk of asthma. Moreover, the expression levels of ORMDL3 and of GSDMB were significantly increased in HRV-stimulated PBMCs, as compared with unstimulated PBMCs. The expression of these genes was associated with 17q21 variants in both conditions, although the increase with exposure to HRV was not genotype-specific. CONCLUSIONS Variants at the 17q21 locus were associated with asthma in children who had had HRV wheezing illnesses and with expression of two genes at this locus. The expression levels of both genes increased in response to HRV stimulation, although the relative increase was not associated with the 17q21 genotypes. (Funded by the National Institutes of Health.)	29	138	2013	10	10.1056/NEJMoa1211592	General & Internal Medicine
Lung Dendritic Cells in Respiratory Viral Infection and Asthma: From Protection to Immunopathology. Lung dendritic cells (DCs) bridge innate and adaptive immunity, and depending on context, they also induce a Th1, Th2, or Th17 response to optimally clear infectious threats. Conversely, lung DCs can also mount maladaptive Th2 immune responses to harmless allergens and, in this way, contribute to immunopathology. It is now clear that the various aspects of DC biology can be understood only if we take into account the functional specializations of different DC subsets that are present in the lung in homeostasis or are attracted to the lung as part of the inflammatory response to inhaled noxious stimuli. Lung DCs are heavily influenced by the nearby epithelial cells, and a model is emerging whereby direct communication between DCs and epithelial cells determines the outcome of the pulmonary immuneresponse. Here, we have approached DC biology from the perspective of viral infection and allergy to illustrate these emerging concepts.. dendritic cells| virus| asthma| allergy|allergic airway inflammation| house-dust mite| cd8(+) t-cell| thymic stromal lymphopoietin| influenza-virus infection| ambient particulate matter| helper type-2 response| blood monocyte subsets| bronchial lymph-node| epithelial-cells.	2012	dendritic cells| virus| asthma| allergy|allergic airway inflammation| house-dust mite| cd8(+) t-cell| thymic stromal lymphopoietin| influenza-virus infection| ambient particulate matter| helper type-2 response| blood monocyte subsets| bronchial lymph-node| epithelial-cells	Lambrecht, BN; Hammad, H	Lung Dendritic Cells in Respiratory Viral Infection and Asthma: From Protection to Immunopathology		ANNUAL REVIEW OF IMMUNOLOGY, VOL 30	dendritic cells; virus; asthma; allergy	ALLERGIC AIRWAY INFLAMMATION; HOUSE-DUST MITE; CD8(+) T-CELL; THYMIC STROMAL LYMPHOPOIETIN; INFLUENZA-VIRUS INFECTION; AMBIENT PARTICULATE MATTER; HELPER TYPE-2 RESPONSE; BLOOD MONOCYTE SUBSETS; BRONCHIAL LYMPH-NODE; EPITHELIAL-CELLS	Lung dendritic cells (DCs) bridge innate and adaptive immunity, and depending on context, they also induce a Th1, Th2, or Th17 response to optimally clear infectious threats. Conversely, lung DCs can also mount maladaptive Th2 immune responses to harmless allergens and, in this way, contribute to immunopathology. It is now clear that the various aspects of DC biology can be understood only if we take into account the functional specializations of different DC subsets that are present in the lung in homeostasis or are attracted to the lung as part of the inflammatory response to inhaled noxious stimuli. Lung DCs are heavily influenced by the nearby epithelial cells, and a model is emerging whereby direct communication between DCs and epithelial cells determines the outcome of the pulmonary immuneresponse. Here, we have approached DC biology from the perspective of viral infection and allergy to illustrate these emerging concepts.	162	138	2012	28	10.1146/annurev-immunol-020711-075021	Immunology
Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: Part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA(2)LEN. Aims: To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis. Mehtods: The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation. Results: The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete. Conclusions: The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.. asthma| allergy| bronchial responsiveness| sports| exercise-induced asthma|cross-country skiers| hyperventilation-induced asthma| ice hockey players| bronchial responsiveness| induced bronchospasm| induced bronchoconstriction| airway inflammation| induced anaphylaxis| cold-air| induced hypoxemia.	APR-2008	asthma| allergy| bronchial responsiveness| sports| exercise-induced asthma|cross-country skiers| hyperventilation-induced asthma| ice hockey players| bronchial responsiveness| induced bronchospasm| induced bronchoconstriction| airway inflammation| induced anaphylaxis| cold-air| induced hypoxemia	Carlsen, KH; Anderson, SD; Bjermer, L; Bonini, S; Brusasco, V; Canonica, W; Cummiskey, J; Delgado, L; Del Giacco, SR; Drobnic, F; Haahtela, T; Larsson, K; Palange, P; Popov, T; van Cauwenberge, P	Exercise-induced asthma, respiratory and allergic disorders in elite athletes: epidemiology, mechanisms and diagnosis: Part I of the report from the Joint Task Force of the European Respiratory Society (ERS) and the European Academy of Allergy and Clinical Immunology (EAACI) in cooperation with GA(2)LEN		ALLERGY	asthma; allergy; bronchial responsiveness; sports; exercise-induced asthma	CROSS-COUNTRY SKIERS; HYPERVENTILATION-INDUCED ASTHMA; ICE HOCKEY PLAYERS; BRONCHIAL RESPONSIVENESS; INDUCED BRONCHOSPASM; INDUCED BRONCHOCONSTRICTION; AIRWAY INFLAMMATION; INDUCED ANAPHYLAXIS; COLD-AIR; INDUCED HYPOXEMIA	Aims: To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis. Mehtods: The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation. Results: The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete. Conclusions: The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.	144	138	2008	17	10.1111/j.1398-9995.2008.01662.x	Allergy; Immunology
Regulatory T cells. Regulatory T (T-R) cells are a subset of T cells that function to control immune responses. Different populations of T-R cells have been described, including thymically derived CD4(+)CD25(+) T-R cells and TO cells induced in the periphery through exposure to antigen. A transcription factor, Foxp3, has been identified that is essential for CD4(+)CD25(+) T-R cell development and function. There is now evidence that transforming growth factor-beta might play a role in this pathway. CD4(+)CD25(+) T-R cells proliferate extensively in vivo in an antigen-specific manner, and can respond to both self and foreign peptides. By suppressing excessive immune responses, T-R cells play a key role in the maintenance of self-tolerance, thus preventing autoimmune disease, as well as inhibiting harmful inflammatory diseases such as asthma and inflammatory bowel disease.. transcription factor foxp3| in-vivo| tgf-beta| cutting edge| dendritic cells| dependent mechanisms| suppressor function| immune pathology| cd4(+)cd25(+)| cd25(+).	AUG-2004	transcription factor foxp3| in-vivo| tgf-beta| cutting edge| dendritic cells| dependent mechanisms| suppressor function| immune pathology| cd4(+)cd25(+)| cd25(+)	Thompson, C; Powrie, F	Regulatory T cells		CURRENT OPINION IN PHARMACOLOGY		TRANSCRIPTION FACTOR FOXP3; IN-VIVO; TGF-BETA; CUTTING EDGE; DENDRITIC CELLS; DEPENDENT MECHANISMS; SUPPRESSOR FUNCTION; IMMUNE PATHOLOGY; CD4(+)CD25(+); CD25(+)	Regulatory T (T-R) cells are a subset of T cells that function to control immune responses. Different populations of T-R cells have been described, including thymically derived CD4(+)CD25(+) T-R cells and TO cells induced in the periphery through exposure to antigen. A transcription factor, Foxp3, has been identified that is essential for CD4(+)CD25(+) T-R cell development and function. There is now evidence that transforming growth factor-beta might play a role in this pathway. CD4(+)CD25(+) T-R cells proliferate extensively in vivo in an antigen-specific manner, and can respond to both self and foreign peptides. By suppressing excessive immune responses, T-R cells play a key role in the maintenance of self-tolerance, thus preventing autoimmune disease, as well as inhibiting harmful inflammatory diseases such as asthma and inflammatory bowel disease.	66	138	2004	7	10.1016/j.coph.2004.05.001	Pharmacology & Pharmacy
"An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages. Background: The recently published GOLD guidelines provide a new system for staging chronic obstructive pulmonary disease (COPD) from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects ""at risk"" of developing the disease. Methods: In order to assess the prevalence of GOLD stages of COPD in high income countries and to evaluate their association with the known risk factors for airflow obstruction, data from the European Community Respiratory Health Survey on more than 18 000 young adults (20-44 years) were analysed. Results: The overall prevalence was 11.8% (95% CI 11.3 to 12.3) for stage 0, 2.5% (95% CI 2.2 to 2.7) for stage I, and 1.1% (95% CI 1.0 to 1.3) for stages II-III. Moderate to heavy smoking (greater than or equal to15 pack years) was significantly associated with both stage 0 (relative risk ratio (RRR) = 4.15; 95% CI 3.55 to 4.84) and stages I+ (RRR = 4.09; 95% CI 3.17 to 5.26), while subjects with stages I+ COPD had a higher likelihood of giving up smoking (RRR = 1.39; 95% CI 1.04 to 1.86) than those with GOLD stage 0 (RRR = 1.05; 95% CI 0.86 to 1.27). Environmental tobacco smoke had the same degree of positive association in both groups. Respiratory infections in childhood and low socioeconomic class were significantly and homogeneously associated with both groups, whereas occupational exposure was significantly associated only with stage 0. All the GOLD stages showed a significantly higher percentage of healthcare resource users than healthy subjects (p < 0.001), with no difference between stage 0 and COPD. Conclusions: A considerable percentage of young adults already suffered from COPD. GOLD stage 0 was characterised by the presence of the same risk factors as COPD and by the same high demand for medical assistance.. respiratory-health-survey| air-flow obstruction| gender-differences| smoking-habits| united-states| copd| mortality| asthma."	FEB 1-2004	respiratory-health-survey| air-flow obstruction| gender-differences| smoking-habits| united-states| copd| mortality| asthma	de Marco, R; Accordini, S; Cerveri, I; Corsico, A; Sunyer, J; Neukirch, F; Kunzli, N; Leynaert, B; Janson, C; Gislason, T; Vermeire, P; Svanes, C; Anto, JM; Burney, P	An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages		THORAX		RESPIRATORY-HEALTH-SURVEY; AIR-FLOW OBSTRUCTION; GENDER-DIFFERENCES; SMOKING-HABITS; UNITED-STATES; COPD; MORTALITY; ASTHMA	"Background: The recently published GOLD guidelines provide a new system for staging chronic obstructive pulmonary disease (COPD) from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects ""at risk"" of developing the disease. Methods: In order to assess the prevalence of GOLD stages of COPD in high income countries and to evaluate their association with the known risk factors for airflow obstruction, data from the European Community Respiratory Health Survey on more than 18 000 young adults (20-44 years) were analysed. Results: The overall prevalence was 11.8% (95% CI 11.3 to 12.3) for stage 0, 2.5% (95% CI 2.2 to 2.7) for stage I, and 1.1% (95% CI 1.0 to 1.3) for stages II-III. Moderate to heavy smoking (greater than or equal to15 pack years) was significantly associated with both stage 0 (relative risk ratio (RRR) = 4.15; 95% CI 3.55 to 4.84) and stages I+ (RRR = 4.09; 95% CI 3.17 to 5.26), while subjects with stages I+ COPD had a higher likelihood of giving up smoking (RRR = 1.39; 95% CI 1.04 to 1.86) than those with GOLD stage 0 (RRR = 1.05; 95% CI 0.86 to 1.27). Environmental tobacco smoke had the same degree of positive association in both groups. Respiratory infections in childhood and low socioeconomic class were significantly and homogeneously associated with both groups, whereas occupational exposure was significantly associated only with stage 0. All the GOLD stages showed a significantly higher percentage of healthcare resource users than healthy subjects (p < 0.001), with no difference between stage 0 and COPD. Conclusions: A considerable percentage of young adults already suffered from COPD. GOLD stage 0 was characterised by the presence of the same risk factors as COPD and by the same high demand for medical assistance."	24	138	2004	6	10.1136/thorax.2003.011163	Respiratory System
Allergens and endotoxin on mothers' mattresses and total immunoglobulin E in cord blood of neonates. The current authors examined whether mite and cat allergen and bacterial endotoxin levels in dust of the mothers' mattresses were associated with cord blood immunoglobulin (Ig)E (CB-IgE) levels in newborns. Data from 1,332 term and normal weight neonates, from an ongoing birth cohort study, Influences of life-style related factors on the immune system and the development of allergies in childhood (LISA), with complete information on exposure to biocontaminants in mattress dust and CB-IgE were analysed. Two thirds of CB-IgE were undetectable (<0.35 kU(.)L(-1)). Thus, 0.35 and 0.45 kU(.)L(-1) (4th quartile) were chosen as cut-offs. Nonparametric smoothing (generalised additive models) showed statistically significant confounder-adjusted associations between elevated CB-IgE levels (greater than or equal to0.45 kU(.)L(-1)) and log-transformed exposures to cat (linear), mite (inverse u-shaped), and endotoxin (u-shaped). After adjustment for covariables, elevated CB-IgE levels (logistic regression using the 1st-4th quartiles of exposure) were positively associated with high cat-allergen exposure and medium exposure to mite allergen, but were inversely associated with exposure to endotoxin. The associations were similar, but somewhat weaker, when 0.35 kU(.)L(-1) was used as cut-off. These results, showing an association between prenatal allergen and endotoxin exposures and immunoglobulin E production, suggest that the development of foetal immune responses may be affected.. cat allergen| cord blood immunoglobulin e| endotoxin| house dust| mite allergen| prenatal exposures|house-dust endotoxin| human immune-system| early-life| environmental allergens| prenatal sensitization| asthma| exposure| responses| pregnancy| gestation.	SEP-2002	cat allergen| cord blood immunoglobulin e| endotoxin| house dust| mite allergen| prenatal exposures|house-dust endotoxin| human immune-system| early-life| environmental allergens| prenatal sensitization| asthma| exposure| responses| pregnancy| gestation	Heinrich, J; Bolte, G; Holscher, B; Douwes, J; Lehmann, I; Fahlbusch, B; Bischof, W; Weiss, M; Borte, M; Wichmann, HE	Allergens and endotoxin on mothers' mattresses and total immunoglobulin E in cord blood of neonates		EUROPEAN RESPIRATORY JOURNAL	cat allergen; cord blood immunoglobulin E; endotoxin; house dust; mite allergen; prenatal exposures	HOUSE-DUST ENDOTOXIN; HUMAN IMMUNE-SYSTEM; EARLY-LIFE; ENVIRONMENTAL ALLERGENS; PRENATAL SENSITIZATION; ASTHMA; EXPOSURE; RESPONSES; PREGNANCY; GESTATION	The current authors examined whether mite and cat allergen and bacterial endotoxin levels in dust of the mothers' mattresses were associated with cord blood immunoglobulin (Ig)E (CB-IgE) levels in newborns. Data from 1,332 term and normal weight neonates, from an ongoing birth cohort study, Influences of life-style related factors on the immune system and the development of allergies in childhood (LISA), with complete information on exposure to biocontaminants in mattress dust and CB-IgE were analysed. Two thirds of CB-IgE were undetectable (<0.35 kU(.)L(-1)). Thus, 0.35 and 0.45 kU(.)L(-1) (4th quartile) were chosen as cut-offs. Nonparametric smoothing (generalised additive models) showed statistically significant confounder-adjusted associations between elevated CB-IgE levels (greater than or equal to0.45 kU(.)L(-1)) and log-transformed exposures to cat (linear), mite (inverse u-shaped), and endotoxin (u-shaped). After adjustment for covariables, elevated CB-IgE levels (logistic regression using the 1st-4th quartiles of exposure) were positively associated with high cat-allergen exposure and medium exposure to mite allergen, but were inversely associated with exposure to endotoxin. The associations were similar, but somewhat weaker, when 0.35 kU(.)L(-1) was used as cut-off. These results, showing an association between prenatal allergen and endotoxin exposures and immunoglobulin E production, suggest that the development of foetal immune responses may be affected.	32	138	2002	7	10.1183/09031936.02.02322001	Respiratory System
Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology. Lipopolysaccharide (LPS), a major proinflammatory glycolipid component of the gram-negative bacterial cell wall, is one of the agents ubiquitously present as contaminant on airborne particles, including air pollution, organic dusts, and cigarette smoke. Chronic exposure to significant levels of LPS is reported to be associated with the development and/or progression of many types of lung diseases, including asthma, chronic bronchitis, and progressive irreversible airflow obstruction, that are all characterized by chronic inflammatory processes in the lung. In the present study, pathologic effects of long-term LPS exposure to the lung were investigated in detail. To this end, a murine model in which mice were exposed to repeated intratracheal instillation of Escherichia coli LPS was developed. We show that long-term LPS instillation in mice results in persistent chronic pulmonary inflammation, characterized by peribronchial and perivascular lymphocytic aggregates (CD4(+), CD8(+), and CD19(+)), parenchymal accumulation of macrophages and CD8+ T cells, and altered cytokine expression. Furthermore, airway and alveolar alterations such as mucus cell metaplasia, airway wall thickening, and irreversible alveolar enlargement accompanied the chronic inflammatory response. Interestingly, the observed inflammatory and pathologic changes mimic changes observed in human subjects with chronic inflammatory lung diseases, especially chronic obstructive pulmonary disease (COPD), suggesting that this murine model could be applicable to dissect the role of inflammation in the pathogenesis of these disease conditions.. obstructive pulmonary-disease| transgenic mice| airway inflammation| cell hyperplasia| cigarette-smoke| cotton dust| grain dust| endotoxin| expression| emphysema.	JAN-2002	obstructive pulmonary-disease| transgenic mice| airway inflammation| cell hyperplasia| cigarette-smoke| cotton dust| grain dust| endotoxin| expression| emphysema	Vernooy, JHJ; Dentener, MA; van Suylen, RJ; Buurman, WA; Wouters, EFM	Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		OBSTRUCTIVE PULMONARY-DISEASE; TRANSGENIC MICE; AIRWAY INFLAMMATION; CELL HYPERPLASIA; CIGARETTE-SMOKE; COTTON DUST; GRAIN DUST; ENDOTOXIN; EXPRESSION; EMPHYSEMA	Lipopolysaccharide (LPS), a major proinflammatory glycolipid component of the gram-negative bacterial cell wall, is one of the agents ubiquitously present as contaminant on airborne particles, including air pollution, organic dusts, and cigarette smoke. Chronic exposure to significant levels of LPS is reported to be associated with the development and/or progression of many types of lung diseases, including asthma, chronic bronchitis, and progressive irreversible airflow obstruction, that are all characterized by chronic inflammatory processes in the lung. In the present study, pathologic effects of long-term LPS exposure to the lung were investigated in detail. To this end, a murine model in which mice were exposed to repeated intratracheal instillation of Escherichia coli LPS was developed. We show that long-term LPS instillation in mice results in persistent chronic pulmonary inflammation, characterized by peribronchial and perivascular lymphocytic aggregates (CD4(+), CD8(+), and CD19(+)), parenchymal accumulation of macrophages and CD8+ T cells, and altered cytokine expression. Furthermore, airway and alveolar alterations such as mucus cell metaplasia, airway wall thickening, and irreversible alveolar enlargement accompanied the chronic inflammatory response. Interestingly, the observed inflammatory and pathologic changes mimic changes observed in human subjects with chronic inflammatory lung diseases, especially chronic obstructive pulmonary disease (COPD), suggesting that this murine model could be applicable to dissect the role of inflammation in the pathogenesis of these disease conditions.	37	138	2002	8		Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Metropolitan home living conditions associated with indoor endotoxin levels. Background: Household endotoxin exposure in allergy and asthma has been gaining attention for its dual potential to exacerbate these conditions in individuals with established disease and to abrogate atopy before disease onset. Objective: We sought to better understand the home environmental and Lifestyle factors influencing house dust endotoxin levels, Methods: From the homes of 86 infants with wheeze in metropolitan Denver, Colorado, house dust endotoxin (detected with a standardized Limulus Amebocyte Lysate assay) and common indoor allergen (Fel d 1, Can f 1, Her p 1, Her f 1, and Bla g 1) contents were quantified. Comprehensive home environment and lifestyle questionnaires were completed during home visits by trained study staff and parents. Results: House dust endotoxin levels were associated with only 2 home environmental features: animals in the home and the presence of central air conditioning. The strongest positive associations were found with animals in the home, Interestingly,the homes without cats or other animals revealed a negative correlation between house dust Fel d 1 and endotoxin (P = .03), Central air conditioning, especially during months of typical use, was associated with lower house dust endotoxin levels, No significant associations between house dust endotoxin levels and home dampness, number of household inhabitants or young children, cleaning frequency, or presence of tobacco smokers in the home were found, Conclusions: Indoor endotoxin exposure can be increased by the presence of animals in the home and decreased with central air conditioning, In some homes without animals, where allergen exposure adequate for sensitization still occurs, there are lower levels of house dust endotoxin, Therefore in homes without animals, factors that influence allergen and endotoxin levels in house dust probably differ, Households with detectable allergen levels but low endotoxin levels may provide a predisposing environment for animal allergen sensitization.. allergy| asthma| prevention| infants| endotoxin| house dust| allergen| animal| cat| dog| air conditioning|in-house dust| hay-fever| environmental endotoxin| bacterial-endotoxin| inhaled endotoxin| cotton dust| asthma| exposure| children| allergen.	MAY-2001	allergy| asthma| prevention| infants| endotoxin| house dust| allergen| animal| cat| dog| air conditioning|in-house dust| hay-fever| environmental endotoxin| bacterial-endotoxin| inhaled endotoxin| cotton dust| asthma| exposure| children| allergen	Gereda, JE; Klinnert, MD; Price, MR; Leung, DYM; Liu, AH	Metropolitan home living conditions associated with indoor endotoxin levels		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; asthma; prevention; infants; endotoxin; house dust; allergen; animal; cat; dog; air conditioning	IN-HOUSE DUST; HAY-FEVER; ENVIRONMENTAL ENDOTOXIN; BACTERIAL-ENDOTOXIN; INHALED ENDOTOXIN; COTTON DUST; ASTHMA; EXPOSURE; CHILDREN; ALLERGEN	Background: Household endotoxin exposure in allergy and asthma has been gaining attention for its dual potential to exacerbate these conditions in individuals with established disease and to abrogate atopy before disease onset. Objective: We sought to better understand the home environmental and Lifestyle factors influencing house dust endotoxin levels, Methods: From the homes of 86 infants with wheeze in metropolitan Denver, Colorado, house dust endotoxin (detected with a standardized Limulus Amebocyte Lysate assay) and common indoor allergen (Fel d 1, Can f 1, Her p 1, Her f 1, and Bla g 1) contents were quantified. Comprehensive home environment and lifestyle questionnaires were completed during home visits by trained study staff and parents. Results: House dust endotoxin levels were associated with only 2 home environmental features: animals in the home and the presence of central air conditioning. The strongest positive associations were found with animals in the home, Interestingly,the homes without cats or other animals revealed a negative correlation between house dust Fel d 1 and endotoxin (P = .03), Central air conditioning, especially during months of typical use, was associated with lower house dust endotoxin levels, No significant associations between house dust endotoxin levels and home dampness, number of household inhabitants or young children, cleaning frequency, or presence of tobacco smokers in the home were found, Conclusions: Indoor endotoxin exposure can be increased by the presence of animals in the home and decreased with central air conditioning, In some homes without animals, where allergen exposure adequate for sensitization still occurs, there are lower levels of house dust endotoxin, Therefore in homes without animals, factors that influence allergen and endotoxin levels in house dust probably differ, Households with detectable allergen levels but low endotoxin levels may provide a predisposing environment for animal allergen sensitization.	43	138	2001	7		Allergy; Immunology
Cockroach allergens and asthma. Asthma and allergy are the most common diseases associated with cockroach infestation of houses in the United States and other parts of the world. Sensitization and exposure to cockroach allergens is associated with increased asthma morbidity in the United States, especially among lower socioeconomic groups, including African American and Hispanic populations. Exposure to cockroach allergens in the first 3 months of life has been associated with repeated wheezing and asthma. The principal domestic cockroach species are Blattella germanica and Periplaneta americana. Both species produce several potent allergens, including Bla g 2 (inactive aspartic proteinase), Bla g 4 (calycin), Bla g 5 (glutathione-S-transferase), the group 1 cross-reactive allergens Bla g 1 and Per a 1, and tropomyosin. Structural homology between tropomyosins from cockroaches, mites, and shrimp may explain clinical cases of the oral allergy syndrome. The 3-dimensional structures of several cockroach allergens are known, and biologically active recombinant allergens have been produced in high-level expression vectors. The use of recombinant cockroach allergens should allow mechanisms of cockroach-induced asthma to be investigated and may lead to the development of new approaches to asthma treatment. Environmental allergen measurements of Bla g 1 and Bla g 2 have allowed exposure levels that cause allergic sensitization to be established. Abatement studies have shown that a sustained decrease in cockroach allergen levels is difficult but can be accomplished by professional application of insecticides, together with rigorous household cleaning. Cockroach asthma is an important public health problem that affects patients who are the least likely to be compliant with treatment with asthma medications or environmental control. Patient education, improvements in the housing stock, and improvements in environmental and immunologic treatment strategies are likely to be the most successful approaches to reduce the prevalence of cockroach-induced asthma.. cockroach| asthma| indoor allergens| public health| risk factors| environment|house-dust mite| immunostimulatory dna-sequences| inner-city children| high-level expression| american cockroach| risk-factors| airway hyperresponsiveness| blattella-germanica| inhalant allergens| shrimp allergen.	MAR-2001	cockroach| asthma| indoor allergens| public health| risk factors| environment|house-dust mite| immunostimulatory dna-sequences| inner-city children| high-level expression| american cockroach| risk-factors| airway hyperresponsiveness| blattella-germanica| inhalant allergens| shrimp allergen	Arruda, LK; Vailes, LD; Ferriani, VPL; Santos, BR; Pomes, A; Chapman, MD	Cockroach allergens and asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	cockroach; asthma; indoor allergens; public health; risk factors; environment	HOUSE-DUST MITE; IMMUNOSTIMULATORY DNA-SEQUENCES; INNER-CITY CHILDREN; HIGH-LEVEL EXPRESSION; AMERICAN COCKROACH; RISK-FACTORS; AIRWAY HYPERRESPONSIVENESS; BLATTELLA-GERMANICA; INHALANT ALLERGENS; SHRIMP ALLERGEN	Asthma and allergy are the most common diseases associated with cockroach infestation of houses in the United States and other parts of the world. Sensitization and exposure to cockroach allergens is associated with increased asthma morbidity in the United States, especially among lower socioeconomic groups, including African American and Hispanic populations. Exposure to cockroach allergens in the first 3 months of life has been associated with repeated wheezing and asthma. The principal domestic cockroach species are Blattella germanica and Periplaneta americana. Both species produce several potent allergens, including Bla g 2 (inactive aspartic proteinase), Bla g 4 (calycin), Bla g 5 (glutathione-S-transferase), the group 1 cross-reactive allergens Bla g 1 and Per a 1, and tropomyosin. Structural homology between tropomyosins from cockroaches, mites, and shrimp may explain clinical cases of the oral allergy syndrome. The 3-dimensional structures of several cockroach allergens are known, and biologically active recombinant allergens have been produced in high-level expression vectors. The use of recombinant cockroach allergens should allow mechanisms of cockroach-induced asthma to be investigated and may lead to the development of new approaches to asthma treatment. Environmental allergen measurements of Bla g 1 and Bla g 2 have allowed exposure levels that cause allergic sensitization to be established. Abatement studies have shown that a sustained decrease in cockroach allergen levels is difficult but can be accomplished by professional application of insecticides, together with rigorous household cleaning. Cockroach asthma is an important public health problem that affects patients who are the least likely to be compliant with treatment with asthma medications or environmental control. Patient education, improvements in the housing stock, and improvements in environmental and immunologic treatment strategies are likely to be the most successful approaches to reduce the prevalence of cockroach-induced asthma.	79	138	2001	10	10.1067/mai.2001.112854	Allergy; Immunology
Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma - Influence of inhaled corticosteroids. This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled beta(2)-agonists with either recently diagnosed asthma (RDA: less than or equal to 2 yr, n = 16) or long-standing asthma (LSA: greater than or equal to 13 yr, n = 16) and at the influence of an intense inhaled corticosteroid (ICS) treatment on these parameters, in relation to changes in airway responsiveness. Patients had a methacholine inhalation test and a bronchoscopy with bronchial biopsies before and after an 8-wk treatment with inhaled fluticasone propionate (FP), 1,000 mu g/day. Baseline FEV1 (mean +/- SEM) was normal and similar in both groups (RDA: 98.1 +/- 2.7, LSA: 94.5 +/- 4.6%). Geometric mean methacholine PC20 was lower in LSA than in RDA (0.44 versus 3.37 mg/ml) at baseline and improved similarly by 1.85 and 1.86 double concentrations with FP treatment. PC20 normalized (greater than or equal to 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm(2) connective tissue surface) for CD3(+), CD4(+), CD8(+), CD25(+), EG1(+), CD45ro(+), and AA1(+) cells were similar in both groups. With FP, EG1(+) (p < 0.001), EG2(+) (p = 0.018), and AA1(+) counts (p = 0.009) decreased significantly in both groups while CD45ro(+) (p = 0.02) counts decreased only in LSA. Baseline type 1 and type 3 collagen deposition underneath the basement membrane was similar in RDA and LSA and did not change significantly after FP. This study shows that recent compared to long-standing mild asthma is associated with a similar degree of airway inflammation and subepithelial fibrosis, and a similar improvement in airway hyperresponsiveness after 8 wk on high-dose ICS. It also indicates that once asthma becomes symptomatic, airway responsiveness cannot normalize in most subjects over such a time period, even with a high dose of ICS.. nonasthmatic subjects| occupational asthma| allergic rhinitis| term treatment| budesonide| methacholine| expression| cessation| steroids| exposure.	OCT-2000	nonasthmatic subjects| occupational asthma| allergic rhinitis| term treatment| budesonide| methacholine| expression| cessation| steroids| exposure	Boulet, LP; Turcotte, H; Laviolette, M; Naud, F; Bernier, MC; Martel, S; Chakir, J	Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma - Influence of inhaled corticosteroids		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		NONASTHMATIC SUBJECTS; OCCUPATIONAL ASTHMA; ALLERGIC RHINITIS; TERM TREATMENT; BUDESONIDE; METHACHOLINE; EXPRESSION; CESSATION; STEROIDS; EXPOSURE	This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled beta(2)-agonists with either recently diagnosed asthma (RDA: less than or equal to 2 yr, n = 16) or long-standing asthma (LSA: greater than or equal to 13 yr, n = 16) and at the influence of an intense inhaled corticosteroid (ICS) treatment on these parameters, in relation to changes in airway responsiveness. Patients had a methacholine inhalation test and a bronchoscopy with bronchial biopsies before and after an 8-wk treatment with inhaled fluticasone propionate (FP), 1,000 mu g/day. Baseline FEV1 (mean +/- SEM) was normal and similar in both groups (RDA: 98.1 +/- 2.7, LSA: 94.5 +/- 4.6%). Geometric mean methacholine PC20 was lower in LSA than in RDA (0.44 versus 3.37 mg/ml) at baseline and improved similarly by 1.85 and 1.86 double concentrations with FP treatment. PC20 normalized (greater than or equal to 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm(2) connective tissue surface) for CD3(+), CD4(+), CD8(+), CD25(+), EG1(+), CD45ro(+), and AA1(+) cells were similar in both groups. With FP, EG1(+) (p < 0.001), EG2(+) (p = 0.018), and AA1(+) counts (p = 0.009) decreased significantly in both groups while CD45ro(+) (p = 0.02) counts decreased only in LSA. Baseline type 1 and type 3 collagen deposition underneath the basement membrane was similar in RDA and LSA and did not change significantly after FP. This study shows that recent compared to long-standing mild asthma is associated with a similar degree of airway inflammation and subepithelial fibrosis, and a similar improvement in airway hyperresponsiveness after 8 wk on high-dose ICS. It also indicates that once asthma becomes symptomatic, airway responsiveness cannot normalize in most subjects over such a time period, even with a high dose of ICS.	36	138	2000	6		General & Internal Medicine; Respiratory System
An optimal bronchial tree may be dangerous. The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling(1) and can ensure minimal dissipation(2-4). The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure(5,6). Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.. model.	FEB 12-2004	model	Mauroy, B; Filoche, M; Weibel, ER; Sapoval, B	An optimal bronchial tree may be dangerous		NATURE		MODEL	The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling(1) and can ensure minimal dissipation(2-4). The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure(5,6). Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.	19	137	2004	4	10.1038/nature02287	Science & Technology - Other Topics
Fresh air in the 21st century?. Ozone is an air quality problem today for much of the world's population. Regions can exceed the ozone air quality standards (AQS) through a combination of local emissions, meteorology favoring pollution episodes, and the clean-air baseline levels of ozone upon which pollution builds. The IPCC 2001 assessment studied a range of global emission scenarios and found that all but one projects increases in global tropospheric ozone during the 21st century. By 2030, near-surface increases over much of the northern hemisphere are estimated to be about 5 ppb (+2 to +7 ppb over the range of scenarios). By 2100 the two more extreme scenarios project baseline ozone increases of >20 ppb, while the other four scenarios give changes of -4 to +10 ppb. Even modest increases in the background abundance of tropospheric ozone might defeat current AQS strategies. The larger increases, however, would gravely threaten both urban and rural air quality over most of the northern hemisphere.. tropospheric ozone| intercontinental transport| pollution| asthma| pollutants| exposure| health.	JAN 31-2003	tropospheric ozone| intercontinental transport| pollution| asthma| pollutants| exposure| health	Prather, M; Gauss, M; Berntsen, T; Isaksen, I; Sundet, J; Bey, I; Brasseur, G; Dentener, F; Derwent, R; Stevenson, D; Grenfell, L; Hauglustaine, D; Horowitz, L; Jacob, D; Mickley, L; Lawrence, M; von Kuhlmann, R; Muller, JF; Pitari, G; Rogers, H; Johnson, M; Pyle, J; Law, K; van Weele, M; Wild, O	Fresh air in the 21st century?		GEOPHYSICAL RESEARCH LETTERS		TROPOSPHERIC OZONE; INTERCONTINENTAL TRANSPORT; POLLUTION; ASTHMA; POLLUTANTS; EXPOSURE; HEALTH	Ozone is an air quality problem today for much of the world's population. Regions can exceed the ozone air quality standards (AQS) through a combination of local emissions, meteorology favoring pollution episodes, and the clean-air baseline levels of ozone upon which pollution builds. The IPCC 2001 assessment studied a range of global emission scenarios and found that all but one projects increases in global tropospheric ozone during the 21st century. By 2030, near-surface increases over much of the northern hemisphere are estimated to be about 5 ppb (+2 to +7 ppb over the range of scenarios). By 2100 the two more extreme scenarios project baseline ozone increases of >20 ppb, while the other four scenarios give changes of -4 to +10 ppb. Even modest increases in the background abundance of tropospheric ozone might defeat current AQS strategies. The larger increases, however, would gravely threaten both urban and rural air quality over most of the northern hemisphere.	21	137	2003	4	10.1029/2002GL016285	Geology
Exposure to cat allergen, maternal history of asthma, and wheezing in first 5 years of life. We looked for an association between early exposure to pets and asthma and wheezing in children whose mothers or fathers did or did not have a history of asthma. We followed up 448 children, who had at least one parent with a history of atopy, from birth to 5 years. Among children whose mothers had no history of asthma, exposure to a cat or a Fel d 1 concentration of at least 8 mug/g at the age of 2-3 months was associated with a reduced risk of wheezing between the ages of 1 and 5 years. However, among children whose mothers did have a history of asthma, such exposures were associated with an increased risk of wheezing at or after the age of 3 years. There was no association between wheezing and exposure to dog or dog allergen, and the father's allergy status had no effect on the relation between childhood wheezing and cat exposure.. children| atopy.	SEP 7-2002	children| atopy	Celedon, JC; Litonjua, AA; Ryan, L; Platts-Mills, T; Weiss, ST; Gold, DR	Exposure to cat allergen, maternal history of asthma, and wheezing in first 5 years of life		LANCET		CHILDREN; ATOPY	We looked for an association between early exposure to pets and asthma and wheezing in children whose mothers or fathers did or did not have a history of asthma. We followed up 448 children, who had at least one parent with a history of atopy, from birth to 5 years. Among children whose mothers had no history of asthma, exposure to a cat or a Fel d 1 concentration of at least 8 mug/g at the age of 2-3 months was associated with a reduced risk of wheezing between the ages of 1 and 5 years. However, among children whose mothers did have a history of asthma, such exposures were associated with an increased risk of wheezing at or after the age of 3 years. There was no association between wheezing and exposure to dog or dog allergen, and the father's allergy status had no effect on the relation between childhood wheezing and cat exposure.	5	137	2002	2	10.1016/S0140-6736(02)09906-3	General & Internal Medicine
Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma. The pathogenesis of aspirin-induced asthma (AIA) has not yet been clearly elucidated, although eicosanoid metabolites appear to play an important role. We hypothesized that levels of eicosanolds in exhaled air condensate are abnormal in patients with AIA and that they change in patients receiving steroid therapy. We measured cysteinyl-leukotrienes (cys-LTs), prostaglandin E-2 (PGE(2)), and leukotriene B-4 (LTB4), and also 8-isoprostane as a marker of oxidative stress, by enzyme immunoassay in exhaled breath condensate from patients with AIA (17 steroid naive; mean age, 41 +/- 23 years; FEV1, 63%pred), 26 patients with aspirin-tolerant asthma (ATA) (11 steroid naive; mean age, 47 +/- 18 years; FEV1, 69%pred), and 16 healthy subjects (mean age, 45 +/- 17 years; FEV1, 93%pred). Cys-LTs were significantly higher in steroid-naive patients with Al compared with steroid-naive patients with ATA and healthy subjects (152.3 +/- 30.4 and 36.6 +/- 7.1 versus 19.4 +/- 2.8 pg/ml; p < 0.05 and p < 0.05, respectively). Steroid-naive patients with AIA also had higher levels of 8-isoprostane than normal subjects (131.8 +/- 31.0 versus 21.9 +/- 4.5 pg/ml; p < 0.05). There were significantly lower levels of both cys-LTs and 8-isoprostanes in steroid-treated patients with AIA. There was no difference in either the PGE(2) or LTB4 level between the patient groups. This is the first study to show that cys-LTs and 8-isoprostanes are elevated in expired breath condensate of steroid-naive patients with AIA, and that cys-LTs are decreased in steroid-treated patients. Exhaled PGE(2) levels are not reduced, so that it is unlikely that a deficiency of PGE(2) is an important mechanism, whereas exhaled LT84 levels are unchanged, indicating an abnormality beyond 5-lipoxygenase.. aspirin-induced asthma| cysteinyl-leukotrienes| exhaled breath condensate| 8-isoprostane| prostaglandin e-2|sensitive asthmatics| oxidative stress| urinary leukotriene-e4| bronchial provocation| intolerant asthma| epithelial-cells| arachidonic-acid| c-4 synthase| in-vivo| condensate.	AUG 1-2002	aspirin-induced asthma| cysteinyl-leukotrienes| exhaled breath condensate| 8-isoprostane| prostaglandin e-2|sensitive asthmatics| oxidative stress| urinary leukotriene-e4| bronchial provocation| intolerant asthma| epithelial-cells| arachidonic-acid| c-4 synthase| in-vivo| condensate	Antczak, A; Montuschi, P; Kharitonov, S; Gorski, P; Barnes, PJ	Increased exhaled cysteinyl-leukotrienes and 8-isoprostane in aspirin-induced asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	aspirin-induced asthma; cysteinyl-leukotrienes; exhaled breath condensate; 8-isoprostane; prostaglandin E-2	SENSITIVE ASTHMATICS; OXIDATIVE STRESS; URINARY LEUKOTRIENE-E4; BRONCHIAL PROVOCATION; INTOLERANT ASTHMA; EPITHELIAL-CELLS; ARACHIDONIC-ACID; C-4 SYNTHASE; IN-VIVO; CONDENSATE	The pathogenesis of aspirin-induced asthma (AIA) has not yet been clearly elucidated, although eicosanoid metabolites appear to play an important role. We hypothesized that levels of eicosanolds in exhaled air condensate are abnormal in patients with AIA and that they change in patients receiving steroid therapy. We measured cysteinyl-leukotrienes (cys-LTs), prostaglandin E-2 (PGE(2)), and leukotriene B-4 (LTB4), and also 8-isoprostane as a marker of oxidative stress, by enzyme immunoassay in exhaled breath condensate from patients with AIA (17 steroid naive; mean age, 41 +/- 23 years; FEV1, 63%pred), 26 patients with aspirin-tolerant asthma (ATA) (11 steroid naive; mean age, 47 +/- 18 years; FEV1, 69%pred), and 16 healthy subjects (mean age, 45 +/- 17 years; FEV1, 93%pred). Cys-LTs were significantly higher in steroid-naive patients with Al compared with steroid-naive patients with ATA and healthy subjects (152.3 +/- 30.4 and 36.6 +/- 7.1 versus 19.4 +/- 2.8 pg/ml; p < 0.05 and p < 0.05, respectively). Steroid-naive patients with AIA also had higher levels of 8-isoprostane than normal subjects (131.8 +/- 31.0 versus 21.9 +/- 4.5 pg/ml; p < 0.05). There were significantly lower levels of both cys-LTs and 8-isoprostanes in steroid-treated patients with AIA. There was no difference in either the PGE(2) or LTB4 level between the patient groups. This is the first study to show that cys-LTs and 8-isoprostanes are elevated in expired breath condensate of steroid-naive patients with AIA, and that cys-LTs are decreased in steroid-treated patients. Exhaled PGE(2) levels are not reduced, so that it is unlikely that a deficiency of PGE(2) is an important mechanism, whereas exhaled LT84 levels are unchanged, indicating an abnormality beyond 5-lipoxygenase.	47	137	2002	6	10.1164/rccm.2101021	General & Internal Medicine; Respiratory System
Does living on a farm during childhood protect against asthma, allergic rhinitis, and atopy in adulthood?. Recent studies of children suggest that factors encountered in a farm environment might protect against the development of allergy. However, it remains uncertain whether living on a farm in childhood is associated with a decreased risk of atopic diseases in adulthood. We analyzed data from 6,251 randomly selected adults 20 to 44 yr of age participating in the European Community Respiratory Health Survey (ECRHS). Subjects answered a detailed questionnaire and underwent specific IgE measurements to five allergens. After adjustment for potential confounders, including pet exposure in childhood, number of siblings, severe respiratory infection in childhood, and parental history of allergy, living on a farm in childhood was associated with a reduced risk of atopic sensitization in adulthood (OR = 0.76, Cl 95% = 0.60-0.97). Compared with other adults, those who had lived on a farm as a child were less frequently sensitized to cat (OR = 0.63, Cl 95% = 0.41-0.96) and to Timothy grass (OR = 0.68, Cl 95% = 0.50-0.94), and were at lower risk of having nasal symptoms in the presence of pollen (OR = 0.80, Cl 95% = 0.64-1.02). The protective effect of farming environment in childhood observed in this population-based sample of young adults provides evidence in favor of the hypothesis that environmental factors encountered in childhood may have a lifelong protective effect against the development of allergy.. asthma| allergic rhinitis| immunologic sensitization| farm| epidemiologic studies|respiratory-health-survey| hay-fever| intestinal microflora| family-size| children| sensitization| prevalence| community| exposure| risk.	NOV 15-2001	asthma| allergic rhinitis| immunologic sensitization| farm| epidemiologic studies|respiratory-health-survey| hay-fever| intestinal microflora| family-size| children| sensitization| prevalence| community| exposure| risk	Leynaert, B; Neukirch, C; Jarvis, D; Chinn, S; Burney, P; Neukirch, F	Does living on a farm during childhood protect against asthma, allergic rhinitis, and atopy in adulthood?		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; allergic rhinitis; immunologic sensitization; farm; epidemiologic studies	RESPIRATORY-HEALTH-SURVEY; HAY-FEVER; INTESTINAL MICROFLORA; FAMILY-SIZE; CHILDREN; SENSITIZATION; PREVALENCE; COMMUNITY; EXPOSURE; RISK	Recent studies of children suggest that factors encountered in a farm environment might protect against the development of allergy. However, it remains uncertain whether living on a farm in childhood is associated with a decreased risk of atopic diseases in adulthood. We analyzed data from 6,251 randomly selected adults 20 to 44 yr of age participating in the European Community Respiratory Health Survey (ECRHS). Subjects answered a detailed questionnaire and underwent specific IgE measurements to five allergens. After adjustment for potential confounders, including pet exposure in childhood, number of siblings, severe respiratory infection in childhood, and parental history of allergy, living on a farm in childhood was associated with a reduced risk of atopic sensitization in adulthood (OR = 0.76, Cl 95% = 0.60-0.97). Compared with other adults, those who had lived on a farm as a child were less frequently sensitized to cat (OR = 0.63, Cl 95% = 0.41-0.96) and to Timothy grass (OR = 0.68, Cl 95% = 0.50-0.94), and were at lower risk of having nasal symptoms in the presence of pollen (OR = 0.80, Cl 95% = 0.64-1.02). The protective effect of farming environment in childhood observed in this population-based sample of young adults provides evidence in favor of the hypothesis that environmental factors encountered in childhood may have a lifelong protective effect against the development of allergy.	37	137	2001	6		General & Internal Medicine; Respiratory System
Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. Atopic individuals are predisposed to mounting vigorous Th2-type immune responses to environmental allergens. To determine the factors responsible, animal models that closely mimic natural modes of allergen exposure should prove most informative. Therefore, we investigated the role of IL-4, a known Th2-promoting cytokine, in generation of Th2 responses after exposure of either the skin or airway to soluble protein. Compared with wild-type (WT) mice, IL-4-deficient (IL-4(-/-)) mice showed markedly impaired Th2 activation after primary exposure to inhaled ovalbumin (OVA), with decreased OVA-specific IgG1 and IgE, and significantly fewer eosinophils in bronchoalveolar lavage (BAL) fluid after airway challenge. In contrast, IL-4(-/-) mice initially exposed to epicutaneous (e.c.) OVA mounted Th2 responses equivalent to responses in WT mice, with high numbers of eosinophils in BAL fluid. Because Th2 responses were not induced by e.c. OVA exposure in Stat6(-/-) mice (mice lacking signal transducer and activator of transcription 6), the role of IL-13 was tested. In vivo depletion of IL-13 prevented Th2 responses induced by e.c. OVA exposure in IL-4(-/-) mice. These data demonstrate a marked difference in the IL-4 dependence of Th2 responses generated at two anatomic sites of natural allergen encounter and identify the skin as a particularly potent site for Th2 sensitization.. cd4+ t-cells| interleukin-4-deficient mice| nippostrongylus-brasiliensis| eosinophilic inflammation| il-4-deficient mice| airway inflammation| aerosolized antigen| cytokine responses| atopic-dermatitis| transgenic mice.	MAR-2000	cd4+ t-cells| interleukin-4-deficient mice| nippostrongylus-brasiliensis| eosinophilic inflammation| il-4-deficient mice| airway inflammation| aerosolized antigen| cytokine responses| atopic-dermatitis| transgenic mice	Herrick, CA; MacLeod, H; Glusac, E; Tigelaar, RE; Bottomly, K	Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4		JOURNAL OF CLINICAL INVESTIGATION		CD4+ T-CELLS; INTERLEUKIN-4-DEFICIENT MICE; NIPPOSTRONGYLUS-BRASILIENSIS; EOSINOPHILIC INFLAMMATION; IL-4-DEFICIENT MICE; AIRWAY INFLAMMATION; AEROSOLIZED ANTIGEN; CYTOKINE RESPONSES; ATOPIC-DERMATITIS; TRANSGENIC MICE	Atopic individuals are predisposed to mounting vigorous Th2-type immune responses to environmental allergens. To determine the factors responsible, animal models that closely mimic natural modes of allergen exposure should prove most informative. Therefore, we investigated the role of IL-4, a known Th2-promoting cytokine, in generation of Th2 responses after exposure of either the skin or airway to soluble protein. Compared with wild-type (WT) mice, IL-4-deficient (IL-4(-/-)) mice showed markedly impaired Th2 activation after primary exposure to inhaled ovalbumin (OVA), with decreased OVA-specific IgG1 and IgE, and significantly fewer eosinophils in bronchoalveolar lavage (BAL) fluid after airway challenge. In contrast, IL-4(-/-) mice initially exposed to epicutaneous (e.c.) OVA mounted Th2 responses equivalent to responses in WT mice, with high numbers of eosinophils in BAL fluid. Because Th2 responses were not induced by e.c. OVA exposure in Stat6(-/-) mice (mice lacking signal transducer and activator of transcription 6), the role of IL-13 was tested. In vivo depletion of IL-13 prevented Th2 responses induced by e.c. OVA exposure in IL-4(-/-) mice. These data demonstrate a marked difference in the IL-4 dependence of Th2 responses generated at two anatomic sites of natural allergen encounter and identify the skin as a particularly potent site for Th2 sensitization.	59	137	2000	11	10.1172/JCI8624	Research & Experimental Medicine
Drowning in disinfection byproducts? Assessing swimming pool water. Disinfection is mandatory for swimming pools: public pools are usually disinfected by gaseous chlorine or sodium hypochlorite and cartridge filters; home pools typically use stabilized chlorine. These methods produce a variety of disinfection byproducts (DBPs), such as trihalomethanes (THMs), which are regulated carcinogenic DBPs in drinking water that have been detected in the blood and breath of swimmers and of nonswimmers at indoor pools. Also produced are halogenated acetic acids (HAAs) and haloketones, which irritate the eyes, skin, and mucous membranes; trichloramine, which is linked with swimming-pool-associated asthma; and halogenated derivatives of UV sun screens, some of which show endocrine effects. Precursors of DBPs include human body substances, chemicals used in cosmetics and sun screens, and natural organic matter. Analytical research has focused also on the identification of an additional portion of unknown DBPs using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS/MS with derivatization. Children swimmers have an increased risk of developing asthma and infections of the respiratory tract and ear. A 1.6-2.0-fold increased risk for bladder cancer has been associated with swimming or showering/bathing with chlorinated water. Bladder cancer risk from THM exposure (all routes combined) was greatest among those with the GSTT1-1 gene. This suggests a mechanism involving distribution of THMs to the bladder by dermal/inhalation exposure and activation there by GSTT1-1 to mutagens. DBPs may be reduced by engineering and behavioral means, such as applying new oxidation and filtration methods, reducing bromide and iodide in the source water, increasing air circulation in indoor pools, and assuring the cleanliness of swimmers. The positive health effects gained by swimming can be increased by reducing the potential adverse health risks.. drinking-water| mutation spectra| birth-weight| trihalomethane concentrations| liquid-chromatography| respiratory symptoms| nitrogen trichloride| chemical-ionization| mass-spectrometry| salmonella ta100.	JAN 15-2007	drinking-water| mutation spectra| birth-weight| trihalomethane concentrations| liquid-chromatography| respiratory symptoms| nitrogen trichloride| chemical-ionization| mass-spectrometry| salmonella ta100	Zwiener, C; Richardson, SD; De Marini, DM; Grummt, T; Glauner, T; Frimmel, FH	Drowning in disinfection byproducts? Assessing swimming pool water		ENVIRONMENTAL SCIENCE & TECHNOLOGY		DRINKING-WATER; MUTATION SPECTRA; BIRTH-WEIGHT; TRIHALOMETHANE CONCENTRATIONS; LIQUID-CHROMATOGRAPHY; RESPIRATORY SYMPTOMS; NITROGEN TRICHLORIDE; CHEMICAL-IONIZATION; MASS-SPECTROMETRY; SALMONELLA TA100	Disinfection is mandatory for swimming pools: public pools are usually disinfected by gaseous chlorine or sodium hypochlorite and cartridge filters; home pools typically use stabilized chlorine. These methods produce a variety of disinfection byproducts (DBPs), such as trihalomethanes (THMs), which are regulated carcinogenic DBPs in drinking water that have been detected in the blood and breath of swimmers and of nonswimmers at indoor pools. Also produced are halogenated acetic acids (HAAs) and haloketones, which irritate the eyes, skin, and mucous membranes; trichloramine, which is linked with swimming-pool-associated asthma; and halogenated derivatives of UV sun screens, some of which show endocrine effects. Precursors of DBPs include human body substances, chemicals used in cosmetics and sun screens, and natural organic matter. Analytical research has focused also on the identification of an additional portion of unknown DBPs using gas chromatography (GC)/mass spectrometry (MS) and liquid chromatography (LC)/MS/MS with derivatization. Children swimmers have an increased risk of developing asthma and infections of the respiratory tract and ear. A 1.6-2.0-fold increased risk for bladder cancer has been associated with swimming or showering/bathing with chlorinated water. Bladder cancer risk from THM exposure (all routes combined) was greatest among those with the GSTT1-1 gene. This suggests a mechanism involving distribution of THMs to the bladder by dermal/inhalation exposure and activation there by GSTT1-1 to mutagens. DBPs may be reduced by engineering and behavioral means, such as applying new oxidation and filtration methods, reducing bromide and iodide in the source water, increasing air circulation in indoor pools, and assuring the cleanliness of swimmers. The positive health effects gained by swimming can be increased by reducing the potential adverse health risks.	88	136	2007	10	10.1021/es062367v	Engineering; Environmental Sciences & Ecology
Early nutrition and immunity - progress and perspectives. The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to 'self', to food and other environmental components, and to commensal bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory diseases. The prevalence of inflammatory diseases, including atopic disorders, has increased over the last 60 years. The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are lifelong processes which start very early in life, even prenatally. Profound immunologic changes occur during pregnancy, involving a polarization of T helper (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in both mother and fetus. This situation is important to maintain pregnancy through avoidance of the rejection of the immunologically incompatible fetus. During the third trimester of human pregnancy, fetal T cells are able to mount antigen-specific responses to environmental and food-derived antigens and antigen-specific T cells are detectable in cord blood in virtually all newborns indicating in utero sensitization. If the neonatal immune system is not able to down-regulate the pre-existing Th2 dominance effectively then an allergic phenotype may develop. Changes occur at, and soon after, birth in order that the immune system of the neonate becomes competent and functional and that the gut becomes colonized with bacteria. Exposure to bacteria during birth and from the mother's skin and the provision of immunologic factors in breast milk are amongst the key events that promote maturation of the infant's gut and gut-associated and systemic immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate immune response upon infection, the ability to develop a tolerogenic response to 'self' and to benign environmental antigens, and the development of immunologic disorders. A Workshop held in February 2006 considered recent findings in the areas of oral tolerance, routes of sensitization to allergens and factors affecting the development of atopic disease; factors influencing the maturation of dendritic cells and the development of regulatory T cells; the influence of gut microflora on immunity, allergic sensitization and infectious disease; the role of nutrition in preventing necrotizing enterocolitis in an animal model of preterm birth; and the role of PUFA of different classes in influencing immune responses and in shaping the development of atopic disease. This report summarizes the content of the lectures and the subsequent discussions.. immunity| infection| allergy| asthma| atopic disease| lymphocyte| dendritic cell| cytokine| inflammation| probiotic| polyunsaturated fatty acid|polyunsaturated fatty-acids| fish-oil supplementation| childhood asthma prevention| gut epithelial monolayers| placebo-controlled trial| regulatory t-cells| atopic disease| allergic sensitization| dendritic cells| double-blind.	OCT-2006	immunity| infection| allergy| asthma| atopic disease| lymphocyte| dendritic cell| cytokine| inflammation| probiotic| polyunsaturated fatty acid|polyunsaturated fatty-acids| fish-oil supplementation| childhood asthma prevention| gut epithelial monolayers| placebo-controlled trial| regulatory t-cells| atopic disease| allergic sensitization| dendritic cells| double-blind	Calder, PC; Krauss-Etschmann, S; de Jong, EC; Dupont, C; Frick, JS; Frokiaer, H; Heinrich, J; Garn, H; Koletzko, S; Lack, G; Mattelio, G; Renz, H; Sangild, PT; Schrezenmeir, J; Stulnig, TM; Thymann, T; Wold, AE; Koletzko, B	Early nutrition and immunity - progress and perspectives		BRITISH JOURNAL OF NUTRITION	immunity; infection; allergy; asthma; atopic disease; lymphocyte; dendritic cell; cytokine; inflammation; probiotic; polyunsaturated fatty acid	POLYUNSATURATED FATTY-ACIDS; FISH-OIL SUPPLEMENTATION; CHILDHOOD ASTHMA PREVENTION; GUT EPITHELIAL MONOLAYERS; PLACEBO-CONTROLLED TRIAL; REGULATORY T-CELLS; ATOPIC DISEASE; ALLERGIC SENSITIZATION; DENDRITIC CELLS; DOUBLE-BLIND	The immune system exists to protect the host against pathogenic organisms and highly complex pathways of recognition, response, elimination and memory have evolved in order to fulfil this role. The immune system also acts to ensure tolerance to 'self', to food and other environmental components, and to commensal bacteria. A breakdown in the tolerogenic pathways can also lead to inflammatory diseases. The prevalence of inflammatory diseases, including atopic disorders, has increased over the last 60 years. The development of tolerance is the result of active immune mechanisms and both development and maintenance of tolerance are lifelong processes which start very early in life, even prenatally. Profound immunologic changes occur during pregnancy, involving a polarization of T helper (Th) cells towards a dominance of Th2 and regulatory T cell effector responses in both mother and fetus. This situation is important to maintain pregnancy through avoidance of the rejection of the immunologically incompatible fetus. During the third trimester of human pregnancy, fetal T cells are able to mount antigen-specific responses to environmental and food-derived antigens and antigen-specific T cells are detectable in cord blood in virtually all newborns indicating in utero sensitization. If the neonatal immune system is not able to down-regulate the pre-existing Th2 dominance effectively then an allergic phenotype may develop. Changes occur at, and soon after, birth in order that the immune system of the neonate becomes competent and functional and that the gut becomes colonized with bacteria. Exposure to bacteria during birth and from the mother's skin and the provision of immunologic factors in breast milk are amongst the key events that promote maturation of the infant's gut and gut-associated and systemic immune systems. The introduction of formula and of solid foods exposes the infant to novel food antigens and also affects the gut flora. Nutrition may be the source of antigens to which the immune system must become tolerant, provide factors, including nutrients, that themselves might modulate immune maturation and responses, and provide factors that influence intestinal flora, which in turn will affect antigen exposure, immune maturation and immune responses. Through these mechanisms it is possible that nutrition early in life might affect later immune competence, the ability to mount an appropriate immune response upon infection, the ability to develop a tolerogenic response to 'self' and to benign environmental antigens, and the development of immunologic disorders. A Workshop held in February 2006 considered recent findings in the areas of oral tolerance, routes of sensitization to allergens and factors affecting the development of atopic disease; factors influencing the maturation of dendritic cells and the development of regulatory T cells; the influence of gut microflora on immunity, allergic sensitization and infectious disease; the role of nutrition in preventing necrotizing enterocolitis in an animal model of preterm birth; and the role of PUFA of different classes in influencing immune responses and in shaping the development of atopic disease. This report summarizes the content of the lectures and the subsequent discussions.	144	136	2006	17	10.1079/BJN20061917	Nutrition & Dietetics
Symptoms of wheeze and persistent cough in the first year of life: Associations with indoor allergens, air contaminants, and maternal history of asthma. In a cohort of 849 infants with an asthmatic sibling, the authors examined the relations of exposure to allergens (dust mite, cockroach, cat, and dog), nitrogen dioxide, and mold with symptoms of wheeze and persistent cough in the first year of life (1998-2000). Among infants whose mothers had physician-diagnosed asthma, neither dust mite allergen nor dog allergen was associated with either symptom. Exposure to cockroach allergen (Bla g 1 at greater than or equal to2 U/g) modestly increased the risk for wheeze (odds ratio (OR)=1.87, 95% confidence interval (CI): 0.94, 3.71), and exposure to cat allergen modestly decreased the risk (OR=0.60, 95% CI: 0.35, 1.03). Among infants of mothers with no asthma history, exposure to gas stoves (OR=1.50, 95% CI: 1.05, 2.15) and wood-burning stoves (OR=2.09, 95% CI: 1.12, 3.91) increased the risk of persistent cough. Similarly, measured nitrogen dioxide concentration was associated with persistent cough (OR=1.21, 95% CI: 1.05, 1.40). Persistent mold affected both infants of mothers with asthma (for wheeze, OR=2.27, 95% CI: 1.27, 4.07; for cough, OR=1.83, 95% CI: 1.04, 3.22) and infants of mothers without asthma (for cough, OR=1.55, 95% CI: 1.04, 2.31). Reported exposure was confirmed by an association of measured fungi with wheeze (OR=1.23, 95% CI: 1.01, 1.49). This appears to have been the first study to measure all of these home exposures (indoor allergens, nitrogen dioxide, fungi) and to prospectively measure the frequency of infant wheeze and persistent cough.. allergens| cockroaches| cough| dust| fungi| infant| nitrogen dioxide| respiratory sounds|infant respiratory symptoms| house-dust mite| childhood asthma| nitrogen-dioxide| parental smoking| united-states| children| exposure| risk| predictors.	AUG 1-2003	allergens| cockroaches| cough| dust| fungi| infant| nitrogen dioxide| respiratory sounds|infant respiratory symptoms| house-dust mite| childhood asthma| nitrogen-dioxide| parental smoking| united-states| children| exposure| risk| predictors	Belanger, K; Beckett, W; Triche, E; Bracken, MB; Holford, T; Ren, P; McSharry, JE; Gold, DR; Platts-Mills, TAE; Leaderer, BP	Symptoms of wheeze and persistent cough in the first year of life: Associations with indoor allergens, air contaminants, and maternal history of asthma		AMERICAN JOURNAL OF EPIDEMIOLOGY	allergens; cockroaches; cough; dust; fungi; infant; nitrogen dioxide; respiratory sounds	INFANT RESPIRATORY SYMPTOMS; HOUSE-DUST MITE; CHILDHOOD ASTHMA; NITROGEN-DIOXIDE; PARENTAL SMOKING; UNITED-STATES; CHILDREN; EXPOSURE; RISK; PREDICTORS	In a cohort of 849 infants with an asthmatic sibling, the authors examined the relations of exposure to allergens (dust mite, cockroach, cat, and dog), nitrogen dioxide, and mold with symptoms of wheeze and persistent cough in the first year of life (1998-2000). Among infants whose mothers had physician-diagnosed asthma, neither dust mite allergen nor dog allergen was associated with either symptom. Exposure to cockroach allergen (Bla g 1 at greater than or equal to2 U/g) modestly increased the risk for wheeze (odds ratio (OR)=1.87, 95% confidence interval (CI): 0.94, 3.71), and exposure to cat allergen modestly decreased the risk (OR=0.60, 95% CI: 0.35, 1.03). Among infants of mothers with no asthma history, exposure to gas stoves (OR=1.50, 95% CI: 1.05, 2.15) and wood-burning stoves (OR=2.09, 95% CI: 1.12, 3.91) increased the risk of persistent cough. Similarly, measured nitrogen dioxide concentration was associated with persistent cough (OR=1.21, 95% CI: 1.05, 1.40). Persistent mold affected both infants of mothers with asthma (for wheeze, OR=2.27, 95% CI: 1.27, 4.07; for cough, OR=1.83, 95% CI: 1.04, 3.22) and infants of mothers without asthma (for cough, OR=1.55, 95% CI: 1.04, 2.31). Reported exposure was confirmed by an association of measured fungi with wheeze (OR=1.23, 95% CI: 1.01, 1.49). This appears to have been the first study to measure all of these home exposures (indoor allergens, nitrogen dioxide, fungi) and to prospectively measure the frequency of infant wheeze and persistent cough.	41	136	2003	8	10.1093/aje/kwg148	Public, Environmental & Occupational Health
Eighteen-month outcomes of house dust mite avoidance and dietary fatty acid modification in the Childhood Asthma Prevention Study (CAPS). Background: Observational studies have linked house dust mite (HDM) exposure and dietary fatty acid intake with asthma in childhood. However, definitive evidence of their role in the etiology of asthma requires a randomized controlled trial. Objective: We hypothesized that the incidence of asthma and allergy in high-risk children would be reduced by avoidance of HDM allergens, supplementation with omega-3 fatty acids, or the combination of these strategies. We present the results of an interim analysis reporting outcomes assessed at 18 months. Methods: A total of 616 pregnant women were randomized to an HDM avoidance intervention, comprising the use of impermeable mattress covers and an acaricide or control and the use of an oil supplement, margarines, and cooking oils containing high levels of omega-3 fatty acids or control. Atopic status was measured by skin prick testing. Symptoms, diagnoses, and medication histories were elicited by means of parental interviews. Results: The diet intervention resulted in a 9.8% absolute reduction (95% CI, 1.5-18.1; P =.02) in the prevalence of any wheeze and a 7.8% absolute reduction (95% CI, 0.5-15.1, P =.04) in prevalence of wheeze of >1 week, but it had no effect on serum IgE, atopy, or doctors' diagnosis of asthma. The HDM avoidance intervention did not affect these outcomes but was associated with a lower use of oral steroids. Conclusion: Increasing dietary omega-3 fatty acids might have a beneficial effect on the prevalence of wheeze during the first 18 months of life. Follow-up to age 5 years, when the effect of the interventions on asthma risk will be assessed, is underway.. allergen avoidance| asthma| atopy| fatty acids| house dust mite| primary prevention|randomized trial| early-life| pregnancy| infancy.	JAN-2003	allergen avoidance| asthma| atopy| fatty acids| house dust mite| primary prevention|randomized trial| early-life| pregnancy| infancy	Mihrshahi, S; Peat, JK; Marks, GB; Mellis, CM; Tovey, ER; Webb, K; Britton, WJ; Leeder, SR	Eighteen-month outcomes of house dust mite avoidance and dietary fatty acid modification in the Childhood Asthma Prevention Study (CAPS)		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen avoidance; asthma; atopy; fatty acids; house dust mite; primary prevention	RANDOMIZED TRIAL; EARLY-LIFE; PREGNANCY; INFANCY	Background: Observational studies have linked house dust mite (HDM) exposure and dietary fatty acid intake with asthma in childhood. However, definitive evidence of their role in the etiology of asthma requires a randomized controlled trial. Objective: We hypothesized that the incidence of asthma and allergy in high-risk children would be reduced by avoidance of HDM allergens, supplementation with omega-3 fatty acids, or the combination of these strategies. We present the results of an interim analysis reporting outcomes assessed at 18 months. Methods: A total of 616 pregnant women were randomized to an HDM avoidance intervention, comprising the use of impermeable mattress covers and an acaricide or control and the use of an oil supplement, margarines, and cooking oils containing high levels of omega-3 fatty acids or control. Atopic status was measured by skin prick testing. Symptoms, diagnoses, and medication histories were elicited by means of parental interviews. Results: The diet intervention resulted in a 9.8% absolute reduction (95% CI, 1.5-18.1; P =.02) in the prevalence of any wheeze and a 7.8% absolute reduction (95% CI, 0.5-15.1, P =.04) in prevalence of wheeze of >1 week, but it had no effect on serum IgE, atopy, or doctors' diagnosis of asthma. The HDM avoidance intervention did not affect these outcomes but was associated with a lower use of oral steroids. Conclusion: Increasing dietary omega-3 fatty acids might have a beneficial effect on the prevalence of wheeze during the first 18 months of life. Follow-up to age 5 years, when the effect of the interventions on asthma risk will be assessed, is underway.	16	136	2003	7	10.1067/mai.2003.36	Allergy; Immunology
Housing characteristics, reported mold exposure, and asthma in the European Community Respiratory Health Survey. Background: The effects of home dampness and mold exposure on adult asthma are not clear. Objective: We aimed to investigate the associations between housing characteristics related to dampness, mold exposure, and house dust mite levels and adult asthma in 38 study centers from the European Community Respiratory Health Survey. Methods: Data about the present home, heating and ventilation systems, double glazing, floor covers, recent water damage, and mold exposure were obtained by means of an interviewer-led questionnaire. The associations between these factors and asthma, as defined on the basis of symptoms in the last year, and of bronchial responsiveness, as determined with methacholine challenge, were evaluated. Odds ratios (ORs) were obtained by using random-effects meta-analyses adjusted within study centers for sex, age group, and smoking status. Results: Fitted carpets and rugs in the bedroom were related to fewer asthma symptoms and bronchial responsiveness (OR range, 0.69-0.91). This effect was consistent across centers and more pronounced among house dust mite-sensitized individuals. Reported mold exposure in the last year was associated with asthma symptoms and bronchial responsiveness (OR range, 1.14-1.44). This effect was homogeneous among centers and stronger in subjects sensitized to Cladosporium species. In centers with a higher prevalence of asthma, the prevalence of reported indoor mold exposure was also high. This association was observed for reported mold exposure by asthmatic subjects (Spearman r(s) = 0.46), as well as reported mold exposure by nonasthmatic subjects (r(s) = 0.54). Reported mold exposure was highest in older houses with recent water damage. Conclusion: We conclude that indoor mold growth has an adverse effect on adult asthma.. asthma| housing| dampness| mold| carpeting| european community respiratory health survey|home dampness| dust mites| fungal propagules| indoor air| symptoms| adults| children| (1->3)-beta-d-glucan| infections| allergens.	AUG-2002	asthma| housing| dampness| mold| carpeting| european community respiratory health survey|home dampness| dust mites| fungal propagules| indoor air| symptoms| adults| children| (1->3)-beta-d-glucan| infections| allergens	Zock, JP; Jarvis, D; Luczynska, C; Sunyer, J; Burney, P	Housing characteristics, reported mold exposure, and asthma in the European Community Respiratory Health Survey		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; housing; dampness; mold; carpeting; European Community Respiratory Health Survey	HOME DAMPNESS; DUST MITES; FUNGAL PROPAGULES; INDOOR AIR; SYMPTOMS; ADULTS; CHILDREN; (1->3)-BETA-D-GLUCAN; INFECTIONS; ALLERGENS	Background: The effects of home dampness and mold exposure on adult asthma are not clear. Objective: We aimed to investigate the associations between housing characteristics related to dampness, mold exposure, and house dust mite levels and adult asthma in 38 study centers from the European Community Respiratory Health Survey. Methods: Data about the present home, heating and ventilation systems, double glazing, floor covers, recent water damage, and mold exposure were obtained by means of an interviewer-led questionnaire. The associations between these factors and asthma, as defined on the basis of symptoms in the last year, and of bronchial responsiveness, as determined with methacholine challenge, were evaluated. Odds ratios (ORs) were obtained by using random-effects meta-analyses adjusted within study centers for sex, age group, and smoking status. Results: Fitted carpets and rugs in the bedroom were related to fewer asthma symptoms and bronchial responsiveness (OR range, 0.69-0.91). This effect was consistent across centers and more pronounced among house dust mite-sensitized individuals. Reported mold exposure in the last year was associated with asthma symptoms and bronchial responsiveness (OR range, 1.14-1.44). This effect was homogeneous among centers and stronger in subjects sensitized to Cladosporium species. In centers with a higher prevalence of asthma, the prevalence of reported indoor mold exposure was also high. This association was observed for reported mold exposure by asthmatic subjects (Spearman r(s) = 0.46), as well as reported mold exposure by nonasthmatic subjects (r(s) = 0.54). Reported mold exposure was highest in older houses with recent water damage. Conclusion: We conclude that indoor mold growth has an adverse effect on adult asthma.	31	136	2002	8	10.1067/mai.2002.126383	Allergy; Immunology
Genome-wide search for atopy susceptibility genes in Dutch families with asthma. Background: Atopy is a phenotype associated with asthma that has a heritable component. However, the role of atopy-susceptibility genes in the development and expression of asthma and allergic disorders is not understood. Objective: We sought to study the familial aggregation and co-occurrence of atopic phenotypes within family members of patients with asthma and to identify chromosomal regions that may contain genes that regulate different atopic phenotypes. Methods: In 200 families (n = 1174) ascertained through a proband with asthma, genome-wide screen and linkage analysis was performed for the following atopic phenotypes: (1) specific IgE to common aeroallergens (Phadiatop assay); (2) specific IgE to Der p 1; (3) positive skin test responses to house dust mite; (4) positive skin test responses to 1 or more of 16 allergens; and (5) peripheral blood eosinophils. Results were compared with the linkage results for total serum IgE levels. Results: There was clear familial aggregation of atopy. A high total serum IgE level in combination with a positive Phadiatop result or a normal total IgE level in combination with a negative Phadiatop result was found in 56.1% of the probands and 66.9% of the offspring. Several chromosomal regions that showed evidence for linkage to an atopic phenotype (ie, 2q, 6p, 7q, and 13q) also showed evidence of linkage with total serum IgE (Xu et al. Am J Hum Genet 2000;67:1163-73). Specific regions of interest for atopic traits were also detected on chromosomes 11q, 17q, and 22q. Conclusions: Atopic phenotypes show familial aggregation, although family members may differ in expression of atopy. Specific chromosomal regions appear to be important in susceptibility to different phenotypes of atopic responsiveness.. genetics of atopy| asthma| specific ige| eosinophils| genoine-wide search|linkage analysis| chromosome 5q31-q33| mite sensitization| founder population| underlying asthma| allergy| markers| screen| locus| hyperresponsiveness.	MAR-2002	genetics of atopy| asthma| specific ige| eosinophils| genoine-wide search|linkage analysis| chromosome 5q31-q33| mite sensitization| founder population| underlying asthma| allergy| markers| screen| locus| hyperresponsiveness	Koppelman, GH; Stine, OC; Xu, JF; Howard, TD; Zheng, SQL; Kauffman, HF; Bleecker, ER; Meyers, DA; Postma, DS	Genome-wide search for atopy susceptibility genes in Dutch families with asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	genetics of atopy; asthma; specific IgE; eosinophils; genoine-wide search	LINKAGE ANALYSIS; CHROMOSOME 5Q31-Q33; MITE SENSITIZATION; FOUNDER POPULATION; UNDERLYING ASTHMA; ALLERGY; MARKERS; SCREEN; LOCUS; HYPERRESPONSIVENESS	Background: Atopy is a phenotype associated with asthma that has a heritable component. However, the role of atopy-susceptibility genes in the development and expression of asthma and allergic disorders is not understood. Objective: We sought to study the familial aggregation and co-occurrence of atopic phenotypes within family members of patients with asthma and to identify chromosomal regions that may contain genes that regulate different atopic phenotypes. Methods: In 200 families (n = 1174) ascertained through a proband with asthma, genome-wide screen and linkage analysis was performed for the following atopic phenotypes: (1) specific IgE to common aeroallergens (Phadiatop assay); (2) specific IgE to Der p 1; (3) positive skin test responses to house dust mite; (4) positive skin test responses to 1 or more of 16 allergens; and (5) peripheral blood eosinophils. Results were compared with the linkage results for total serum IgE levels. Results: There was clear familial aggregation of atopy. A high total serum IgE level in combination with a positive Phadiatop result or a normal total IgE level in combination with a negative Phadiatop result was found in 56.1% of the probands and 66.9% of the offspring. Several chromosomal regions that showed evidence for linkage to an atopic phenotype (ie, 2q, 6p, 7q, and 13q) also showed evidence of linkage with total serum IgE (Xu et al. Am J Hum Genet 2000;67:1163-73). Specific regions of interest for atopic traits were also detected on chromosomes 11q, 17q, and 22q. Conclusions: Atopic phenotypes show familial aggregation, although family members may differ in expression of atopy. Specific chromosomal regions appear to be important in susceptibility to different phenotypes of atopic responsiveness.	34	136	2002	9	10.1067/mai.2002.122235	Allergy; Immunology
Asthma in preschool children: prevalence and risk factors. Background-The prevalence of asthma in children has increased in many countries over recent years. To plan effective interventions to reverse this trend we need a better understanding of the risk factors for asthma in early life. This study was undertaken to measure the prevalence of, and risk factors for, asthma in preschool children. Methods-Parents of children aged 3-5 years living in two cities (Lismore, n=383; Wagga Wagga, n=591) in New South Wales, Australia were surveyed by questionnaire to ascertain the presence of asthma and various proposed risk factors for asthma in their children. Recent asthma was defined as ever having been diagnosed with asthma and having cough or wheeze in the last 12 months and having used an asthma medication in the last 12 months. Atopy was measured by skin prick tests to six common allergens. Results-The prevalence of recent asthma was 22% in Lismore and 18% in Wagga Wagga. Factors which increased the risk of recent asthma were: atopy (odds ratio (OR) 2.35, 95% CI 1.49 to 3.72), having a parent with a history of asthma (OR 2.05, 95% CI 1.34 to 3.16), having had a serious respiratory infection in the first 2 years of life (OR 1.93, 95% CI 1.25 to 2.99), and a high dietary intake of polyunsaturated fats (OR 2.03, 95% CI 1.15 to 3.60). Breast feeding (OR 0.41, 95% CI 0.22 to 0.74) and having three or more older siblings (OR 0.16, 95% CI 0.04 to 0.71) decreased the risk of recent asthma. Conclusions-Of the factors tested, those that have the greatest potential to be modified to reduce the risk of asthma are breast feeding and consumption of polyunsaturated fats.. asthma| prevalence| risk factors| preschool children|house-dust mite| childhood asthma| atopic disease| allergen avoidance| family-size| hay-fever| association| age| sensitivity| severity.	AUG-2001	asthma| prevalence| risk factors| preschool children|house-dust mite| childhood asthma| atopic disease| allergen avoidance| family-size| hay-fever| association| age| sensitivity| severity	Haby, MM; Peat, JK; Marks, GB; Woolcock, AJ; Leeder, SR	Asthma in preschool children: prevalence and risk factors		THORAX	asthma; prevalence; risk factors; preschool children	HOUSE-DUST MITE; CHILDHOOD ASTHMA; ATOPIC DISEASE; ALLERGEN AVOIDANCE; FAMILY-SIZE; HAY-FEVER; ASSOCIATION; AGE; SENSITIVITY; SEVERITY	Background-The prevalence of asthma in children has increased in many countries over recent years. To plan effective interventions to reverse this trend we need a better understanding of the risk factors for asthma in early life. This study was undertaken to measure the prevalence of, and risk factors for, asthma in preschool children. Methods-Parents of children aged 3-5 years living in two cities (Lismore, n=383; Wagga Wagga, n=591) in New South Wales, Australia were surveyed by questionnaire to ascertain the presence of asthma and various proposed risk factors for asthma in their children. Recent asthma was defined as ever having been diagnosed with asthma and having cough or wheeze in the last 12 months and having used an asthma medication in the last 12 months. Atopy was measured by skin prick tests to six common allergens. Results-The prevalence of recent asthma was 22% in Lismore and 18% in Wagga Wagga. Factors which increased the risk of recent asthma were: atopy (odds ratio (OR) 2.35, 95% CI 1.49 to 3.72), having a parent with a history of asthma (OR 2.05, 95% CI 1.34 to 3.16), having had a serious respiratory infection in the first 2 years of life (OR 1.93, 95% CI 1.25 to 2.99), and a high dietary intake of polyunsaturated fats (OR 2.03, 95% CI 1.15 to 3.60). Breast feeding (OR 0.41, 95% CI 0.22 to 0.74) and having three or more older siblings (OR 0.16, 95% CI 0.04 to 0.71) decreased the risk of recent asthma. Conclusions-Of the factors tested, those that have the greatest potential to be modified to reduce the risk of asthma are breast feeding and consumption of polyunsaturated fats.	34	136	2001	7	10.1136/thorax.56.8.589	Respiratory System
Community-acquired pneumonia in the elderly. Pneumonia in the elderly is a common and serious problem with a clinical presentation that can differ from that in younger patients. Older patients with pneumonia complain of significantly fewer symptoms than do younger patients, and delirium commonly occurs. Indeed, delirium may be the only manifestation of pneumonia in this group of patients. Alcoholism, asthma, immunosuppression, and age >70 years are risk factors for community-acquired pneumonia in the elderly. Among nursing home residents, the following are risk factors for pneumonia: advanced age, male sex, difficulty in swallowing, inability to take oral medications, profound disability, bedridden state, and urinary incontinence. Streptococcus pneumoniae is the most common cause of pneumonia among the elderly Aspiration pneumonia is underdiagnosed in this group of patients, and tuberculosis always should be considered. In this population an etiologic diagnosis is rarely available when antimicrobial therapy must be instituted. Use of the guidelines for treatment of pneumonia issued by the Infectious Diseases Society of America, with modification for treatment in the nursing home setting, is recommended.. resistant streptococcus-pneumoniae| initial antimicrobial therapy| respiratory-tract infections| nursing-home residents| term-care facilities| risk-factors| hospitalized-patients| penicillin-resistant| randomized trial| requiring hospitalization.	OCT-2000	resistant streptococcus-pneumoniae| initial antimicrobial therapy| respiratory-tract infections| nursing-home residents| term-care facilities| risk-factors| hospitalized-patients| penicillin-resistant| randomized trial| requiring hospitalization	Marrie, TJ	Community-acquired pneumonia in the elderly		CLINICAL INFECTIOUS DISEASES		RESISTANT STREPTOCOCCUS-PNEUMONIAE; INITIAL ANTIMICROBIAL THERAPY; RESPIRATORY-TRACT INFECTIONS; NURSING-HOME RESIDENTS; TERM-CARE FACILITIES; RISK-FACTORS; HOSPITALIZED-PATIENTS; PENICILLIN-RESISTANT; RANDOMIZED TRIAL; REQUIRING HOSPITALIZATION	Pneumonia in the elderly is a common and serious problem with a clinical presentation that can differ from that in younger patients. Older patients with pneumonia complain of significantly fewer symptoms than do younger patients, and delirium commonly occurs. Indeed, delirium may be the only manifestation of pneumonia in this group of patients. Alcoholism, asthma, immunosuppression, and age >70 years are risk factors for community-acquired pneumonia in the elderly. Among nursing home residents, the following are risk factors for pneumonia: advanced age, male sex, difficulty in swallowing, inability to take oral medications, profound disability, bedridden state, and urinary incontinence. Streptococcus pneumoniae is the most common cause of pneumonia among the elderly Aspiration pneumonia is underdiagnosed in this group of patients, and tuberculosis always should be considered. In this population an etiologic diagnosis is rarely available when antimicrobial therapy must be instituted. Use of the guidelines for treatment of pneumonia issued by the Infectious Diseases Society of America, with modification for treatment in the nursing home setting, is recommended.	126	136	2000	13	10.1086/318124	Immunology; Infectious Diseases; Microbiology
"The epidemiology of glioma in adults: a ""state of the science"" review. Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (similar to 45% of all gliomas), has a 5-year relative survival of similar to 5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O-6-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a ""state of the science"" review of current research into causes and risk factors for gliomas in adults.. brain tumors| epidemiology| genome-wide association studies| glioma| risk factors|central-nervous-system| upper midwest health| magnetic-field exposure| high-grade glioma| mobile phone use| single-nucleotide polymorphisms| integrated genomic analysis| childhood-cancer survivor| occupational risk-factors| population-based analysis."	JUL-2014	brain tumors| epidemiology| genome-wide association studies| glioma| risk factors|central-nervous-system| upper midwest health| magnetic-field exposure| high-grade glioma| mobile phone use| single-nucleotide polymorphisms| integrated genomic analysis| childhood-cancer survivor| occupational risk-factors| population-based analysis	Ostrom, QT; Bauchet, L; Davis, FG; Deltour, I; Fisher, JL; Langer, CE; Pekmezci, M; Schwartzbaum, JA; Turner, MC; Walsh, KM; Wrensch, MR; Barnholtz-Sloan, JS	"The epidemiology of glioma in adults: a ""state of the science"" review"		NEURO-ONCOLOGY	brain tumors; epidemiology; genome-wide association studies; glioma; risk factors	CENTRAL-NERVOUS-SYSTEM; UPPER MIDWEST HEALTH; MAGNETIC-FIELD EXPOSURE; HIGH-GRADE GLIOMA; MOBILE PHONE USE; SINGLE-NUCLEOTIDE POLYMORPHISMS; INTEGRATED GENOMIC ANALYSIS; CHILDHOOD-CANCER SURVIVOR; OCCUPATIONAL RISK-FACTORS; POPULATION-BASED ANALYSIS	"Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (similar to 45% of all gliomas), has a 5-year relative survival of similar to 5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O-6-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a ""state of the science"" review of current research into causes and risk factors for gliomas in adults."	157	135	2014	18	10.1093/neuonc/nou087	Oncology; Neurosciences & Neurology
Allergens in wheat and related cereals. Wheat is one of the major crops grown, processed and consumed by humankind and is associated with both intolerances (notably coeliac disease) and allergies. Two types of allergy are particularly well characterized. The first is bakers' asthma, which results from the inhalation of flour and dust during grain processing. Although a number of wheat proteins have been shown to bind IgE from patients with bakers' asthma, there is no doubt a well-characterized group of inhibitors of alpha-amylase (also called chloroform methanol soluble, or CM, proteins) are the major components responsible for this syndrome. The second well-characterized form of allergy to wheat proteins is wheat-dependent exercise-induced anaphylaxis (WDEIA), with the omega(5)-gliadins (part of the gluten protein fraction) being the major group of proteins which are responsible. Other forms of food allergy have also been reported, with the proteins responsible including gluten proteins, CM proteins and non-specific lipid transfer proteins. Processing of wheat and of related cereals (barley and rye, which may contain related allergens) may lead to decreased allergenicity while genetic engineering technology offers opportunities to eliminate allergens by suppressing gene expression.. allergy| cereals| wheat|exercise-induced anaphylaxis| alpha-amylase-inhibitor| lipid transfer protein| controlled food challenge| ige-binding epitope| aspergillus-derived enzymes| bakers asthma disease| low-molecular-weight| major allergen| omega-5 gliadin.	NOV-2008	allergy| cereals| wheat|exercise-induced anaphylaxis| alpha-amylase-inhibitor| lipid transfer protein| controlled food challenge| ige-binding epitope| aspergillus-derived enzymes| bakers asthma disease| low-molecular-weight| major allergen| omega-5 gliadin	Tatham, AS; Shewry, PR	Allergens in wheat and related cereals		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; cereals; wheat	EXERCISE-INDUCED ANAPHYLAXIS; ALPHA-AMYLASE-INHIBITOR; LIPID TRANSFER PROTEIN; CONTROLLED FOOD CHALLENGE; IGE-BINDING EPITOPE; ASPERGILLUS-DERIVED ENZYMES; BAKERS ASTHMA DISEASE; LOW-MOLECULAR-WEIGHT; MAJOR ALLERGEN; OMEGA-5 GLIADIN	Wheat is one of the major crops grown, processed and consumed by humankind and is associated with both intolerances (notably coeliac disease) and allergies. Two types of allergy are particularly well characterized. The first is bakers' asthma, which results from the inhalation of flour and dust during grain processing. Although a number of wheat proteins have been shown to bind IgE from patients with bakers' asthma, there is no doubt a well-characterized group of inhibitors of alpha-amylase (also called chloroform methanol soluble, or CM, proteins) are the major components responsible for this syndrome. The second well-characterized form of allergy to wheat proteins is wheat-dependent exercise-induced anaphylaxis (WDEIA), with the omega(5)-gliadins (part of the gluten protein fraction) being the major group of proteins which are responsible. Other forms of food allergy have also been reported, with the proteins responsible including gluten proteins, CM proteins and non-specific lipid transfer proteins. Processing of wheat and of related cereals (barley and rye, which may contain related allergens) may lead to decreased allergenicity while genetic engineering technology offers opportunities to eliminate allergens by suppressing gene expression.	139	135	2008	15	10.1111/j.1365-2222.2008.03101.x	Allergy; Immunology
The relationship between obesity and asthma severity and control in adults. Background: The association of obesity with asthma outcomes is not well understood. Objective: The objective of this study was to examine the association of obesity, as represented by a body mass index (BMI) of greater than 30 kg/m(2), with quality-of-life scores, asthma control problems, and asthma-related hospitalizations. Methods: The study followed a cross-sectional design. Questionnaires were completed at home by a random sample of 1113 members of a large integrated health care organization who were 35 years of age or older with health care use suggestive of active asthma. Outcomes included the mini-Asthma Quality of Life Questionnaire, the Asthma Therapy Assessment Questionnaire, and self-reported asthma-related hospitalization. Several other factors known to influence asthma outcomes also were collected: demographics, smoking status, oral corticosteroid use in the past month, evidence of gastroesophageal reflux disease, and inhaled corticosteroid use in the past month. Multiple logistic regression models were used to measure the association of BMI status with outcomes. Results: Even after adjusting for demographics, smoking status, oral corticosteroid use, evidence of gastroesophageal reflux disease, and inhaled corticosteroid use, obese adults were more likely than those with normal BMIs (<25 k g/m(2)) to report poor asthma-specific quality of life (odds ratio [OR], 2.8; 95% Cl, 1.6-4.9), poor asthma control (OR, 2.7; 95% Cl, 1.7-4.3), and a history of asthma-related hospitalizations (OR, 4.6; 95% Cl, 1.4-14.4). Conclusions: Our findings suggest that obesity is associated with worse asthma outcomes, especially an increased risk of asthma related hospitalizations.. asthma| quality of life| obesity| hospitalization| inhaled| corticosleroids|body-mass index| quality-of-life| health-care utilization| weight-reduction| association| prevalence| overweight| trends| women.	SEP-2008	asthma| quality of life| obesity| hospitalization| inhaled| corticosleroids|body-mass index| quality-of-life| health-care utilization| weight-reduction| association| prevalence| overweight| trends| women	Mosen, DM; Schatz, M; Magid, DJ; Carnargo, CA	The relationship between obesity and asthma severity and control in adults		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; quality of life; obesity; hospitalization; inhaled; corticosleroids	BODY-MASS INDEX; QUALITY-OF-LIFE; HEALTH-CARE UTILIZATION; WEIGHT-REDUCTION; ASSOCIATION; PREVALENCE; OVERWEIGHT; TRENDS; WOMEN	Background: The association of obesity with asthma outcomes is not well understood. Objective: The objective of this study was to examine the association of obesity, as represented by a body mass index (BMI) of greater than 30 kg/m(2), with quality-of-life scores, asthma control problems, and asthma-related hospitalizations. Methods: The study followed a cross-sectional design. Questionnaires were completed at home by a random sample of 1113 members of a large integrated health care organization who were 35 years of age or older with health care use suggestive of active asthma. Outcomes included the mini-Asthma Quality of Life Questionnaire, the Asthma Therapy Assessment Questionnaire, and self-reported asthma-related hospitalization. Several other factors known to influence asthma outcomes also were collected: demographics, smoking status, oral corticosteroid use in the past month, evidence of gastroesophageal reflux disease, and inhaled corticosteroid use in the past month. Multiple logistic regression models were used to measure the association of BMI status with outcomes. Results: Even after adjusting for demographics, smoking status, oral corticosteroid use, evidence of gastroesophageal reflux disease, and inhaled corticosteroid use, obese adults were more likely than those with normal BMIs (<25 k g/m(2)) to report poor asthma-specific quality of life (odds ratio [OR], 2.8; 95% Cl, 1.6-4.9), poor asthma control (OR, 2.7; 95% Cl, 1.7-4.3), and a history of asthma-related hospitalizations (OR, 4.6; 95% Cl, 1.4-14.4). Conclusions: Our findings suggest that obesity is associated with worse asthma outcomes, especially an increased risk of asthma related hospitalizations.	27	135	2008	5	10.1016/j.jaci.2008.06.024	Allergy; Immunology
Climate change and allergic disease. Climate change is potentially the largest global threat to human health ever encountered. The earth is warming, the warming is accelerating, and human actions are largely responsible. If current emissions and land use trends continue unchecked, the next generations will face more injury, disease, and death related to natural disasters and heat waves, higher rates of climate-related infections, and wide-spread malnutrition, as well as more allergic and air pollution-related morbidity and mortality. This review highlights links between global climate change and anticipated increases in prevalence and severity of asthma and related allergic disease mediated through worsening ambient air pollution and altered local and regional pollen production. The pattern of change will vary regionally depending on latitude, altitude, rainfall and storms, land-use patterns, urbanization, transportation, and energy production. The magnitude of climate change and related increases in allergic disease will be affected by how aggressively greenhouse gas mitigation strategies are pursued, but at best an average warming of I to 2 degrees C is certain this century. Thus, anticipation of a higher allergic disease burden will affect clinical practice as well as public health planning. A number of practical primary and secondary prevention strategies are suggested at the end of the review to assist in meeting this unprecedented public health challenge.. climate change| global warming| pollen| air pollution| ozone| allergic rhinitis| asthma| mitigation| adaptation| prevention|ragweed ambrosia-artemisiifolia| particulate air-pollution| elevated atmospheric co2| diesel exhaust particles| asthmatic-children| mexico-city| nitrogen-dioxide| childhood asthma| ozone exposure| ambient ozone.	SEP-2008	climate change| global warming| pollen| air pollution| ozone| allergic rhinitis| asthma| mitigation| adaptation| prevention|ragweed ambrosia-artemisiifolia| particulate air-pollution| elevated atmospheric co2| diesel exhaust particles| asthmatic-children| mexico-city| nitrogen-dioxide| childhood asthma| ozone exposure| ambient ozone	Shea, KM; Truckner, RT; Weber, RW; Peden, DB	Climate change and allergic disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	climate change; global warming; pollen; air pollution; ozone; allergic rhinitis; asthma; mitigation; adaptation; prevention	RAGWEED AMBROSIA-ARTEMISIIFOLIA; PARTICULATE AIR-POLLUTION; ELEVATED ATMOSPHERIC CO2; DIESEL EXHAUST PARTICLES; ASTHMATIC-CHILDREN; MEXICO-CITY; NITROGEN-DIOXIDE; CHILDHOOD ASTHMA; OZONE EXPOSURE; AMBIENT OZONE	Climate change is potentially the largest global threat to human health ever encountered. The earth is warming, the warming is accelerating, and human actions are largely responsible. If current emissions and land use trends continue unchecked, the next generations will face more injury, disease, and death related to natural disasters and heat waves, higher rates of climate-related infections, and wide-spread malnutrition, as well as more allergic and air pollution-related morbidity and mortality. This review highlights links between global climate change and anticipated increases in prevalence and severity of asthma and related allergic disease mediated through worsening ambient air pollution and altered local and regional pollen production. The pattern of change will vary regionally depending on latitude, altitude, rainfall and storms, land-use patterns, urbanization, transportation, and energy production. The magnitude of climate change and related increases in allergic disease will be affected by how aggressively greenhouse gas mitigation strategies are pursued, but at best an average warming of I to 2 degrees C is certain this century. Thus, anticipation of a higher allergic disease burden will affect clinical practice as well as public health planning. A number of practical primary and secondary prevention strategies are suggested at the end of the review to assist in meeting this unprecedented public health challenge.	120	135	2008	11	10.1016/j.jaci.2008.06.032	Allergy; Immunology
Emergency treatment of anaphylactic reactions - Guidelines for healthcare providers. The UK incidence of anaphylactic reactions is increasing. Patients who have an anaphylactic reaction have life-threatening airway and, or breathing and, or circulation problems usually associated with skin or mucosal changes. Patients having an anaphylactic reaction should be treated using the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. Anaphylactic reactions are not easy to study with randomised controlled trials. There are, however, systematic reviews of the available evidence and a wealth of clinical experience to help formulate guidelines. The exact treatment will depend on the patient's location, the equipment and drugs available, and the skills of those treating the anaphylactic reaction. Early treatment with intramuscular adrenaline is the treatment of choice for patients having an anaphylactic reaction. Despite previous guidelines, there is still confusion about the indications, dose and route of adrenaline. Intravenous adrenaline must only be used in certain specialist settings and only by those skilled and experienced in its use. All those who are suspected of having had an anaphylactic reaction should be referred to a specialist in allergy. Individuals who are at high risk of an anaphylactic reaction should carry an adrenaline auto-injector and receive training and support in its use. There is a need for further research about the diagnosis, treatment and prevention of anaphylactic reactions. (C) 2008 Resuscitation Council (UK). Published by Elsevier Ireland Ltd.. anaphylactic reactions| treatment|resuscitation-council guidelines| epinephrine absorption| allergic reactions| life-support| management| children| shock| adrenaline| epidemiology| vasopressin.	MAY-2008	anaphylactic reactions| treatment|resuscitation-council guidelines| epinephrine absorption| allergic reactions| life-support| management| children| shock| adrenaline| epidemiology| vasopressin	Soar, J; Pumphrey, R; Cant, A; Clarke, S; Corbett, A; Dawson, P; Ewan, P; Foex, B; Gabbott, D; Griffiths, M; Hall, J; Harper, N; Jewkes, F; Maconochie, I; Mitchell, S; Nasser, S; Nolan, J; Rylance, G; Sheikh, A; Unsworth, DJ; Warrell, D	Emergency treatment of anaphylactic reactions - Guidelines for healthcare providers		RESUSCITATION	anaphylactic reactions; treatment	RESUSCITATION-COUNCIL GUIDELINES; EPINEPHRINE ABSORPTION; ALLERGIC REACTIONS; LIFE-SUPPORT; MANAGEMENT; CHILDREN; SHOCK; ADRENALINE; EPIDEMIOLOGY; VASOPRESSIN	The UK incidence of anaphylactic reactions is increasing. Patients who have an anaphylactic reaction have life-threatening airway and, or breathing and, or circulation problems usually associated with skin or mucosal changes. Patients having an anaphylactic reaction should be treated using the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach. Anaphylactic reactions are not easy to study with randomised controlled trials. There are, however, systematic reviews of the available evidence and a wealth of clinical experience to help formulate guidelines. The exact treatment will depend on the patient's location, the equipment and drugs available, and the skills of those treating the anaphylactic reaction. Early treatment with intramuscular adrenaline is the treatment of choice for patients having an anaphylactic reaction. Despite previous guidelines, there is still confusion about the indications, dose and route of adrenaline. Intravenous adrenaline must only be used in certain specialist settings and only by those skilled and experienced in its use. All those who are suspected of having had an anaphylactic reaction should be referred to a specialist in allergy. Individuals who are at high risk of an anaphylactic reaction should carry an adrenaline auto-injector and receive training and support in its use. There is a need for further research about the diagnosis, treatment and prevention of anaphylactic reactions. (C) 2008 Resuscitation Council (UK). Published by Elsevier Ireland Ltd.	77	135	2008	13	10.1016/j.resuscitation.2008.02.001	General & Internal Medicine; Emergency Medicine
Health effects associated with exposure to ambient air pollution. The World Health Organization has identified ambient air pollution as a high public health priority, based on estimates of air pollution related death and disability-adjusted life years derived in its Global Burden of Disease initiative. The NERAM Colloquium Series on Health and Air Quality was initiated to strengthen the linkage between scientists, policymakers, and other stakeholders by reviewing the current state of science, identifying policy-relevant gaps and uncertainties in the scientific evidence, and proposing a path forward for research and policy to improve air quality and public health. The objective of this paper is to review the current state of science addressing the impacts of air pollution on human health. The paper is one of four background papers prepared for the 2003 NERAM/AirNet Conference on Strategies for Clean Air and Health, the third meeting in the international Colloquium Series. The review is based on the framework and findings of the U. S. National Research Committee (NRC) on Research Priorities for Airborne Particulate Matter and addresses key questions underlying air quality risk management policy decisions.. long-term exposure| american-cancer-society| all-cause mortality| harvard 6 cities| particulate matter| time-series| respiratory-diseases| canadian cities| case-crossover| asthma hospitalization.	FEB 1-2007	long-term exposure| american-cancer-society| all-cause mortality| harvard 6 cities| particulate matter| time-series| respiratory-diseases| canadian cities| case-crossover| asthma hospitalization	Samet, J; Krewski, D	Health effects associated with exposure to ambient air pollution		JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES		LONG-TERM EXPOSURE; AMERICAN-CANCER-SOCIETY; ALL-CAUSE MORTALITY; HARVARD 6 CITIES; PARTICULATE MATTER; TIME-SERIES; RESPIRATORY-DISEASES; CANADIAN CITIES; CASE-CROSSOVER; ASTHMA HOSPITALIZATION	The World Health Organization has identified ambient air pollution as a high public health priority, based on estimates of air pollution related death and disability-adjusted life years derived in its Global Burden of Disease initiative. The NERAM Colloquium Series on Health and Air Quality was initiated to strengthen the linkage between scientists, policymakers, and other stakeholders by reviewing the current state of science, identifying policy-relevant gaps and uncertainties in the scientific evidence, and proposing a path forward for research and policy to improve air quality and public health. The objective of this paper is to review the current state of science addressing the impacts of air pollution on human health. The paper is one of four background papers prepared for the 2003 NERAM/AirNet Conference on Strategies for Clean Air and Health, the third meeting in the international Colloquium Series. The review is based on the framework and findings of the U. S. National Research Committee (NRC) on Research Priorities for Airborne Particulate Matter and addresses key questions underlying air quality risk management policy decisions.	97	135	2007	16	10.1080/15287390600884644	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Review on safety of the entomopathogenic fungus Metarhizium anisopliae. The entomopathogenic fungus Metarhizium anisopliae (Metschn.) Sorokin is widely used for biocontrol of pest insects, and many commercial products are on the market or under development. The aim of this review is to summarise all relevant safety data of this fungus, which are necessary for the commercialisation and registration process. The review contains the following sections: (1) identity, (2) biological properties (history, natural occurrence and geographical distribution, host range, mode of action, production of metabolites/toxins, effect of environmental factors), (3) methods to determine and quantify residues, (4) fate and behaviour in the environment (mobility and persistence in air, water and soil), (5) effects on non-target organisms (microorganisms, plants, soil organisms, aquatic organisms, predators, parasitoids, honey bees, earth worms, etc.), (6) effects on vertebrates (fish, amphibia, reptiles, and birds), and (7) effects on mammals and human health (allergy, pathogenicity/toxicity). On the basis of the presented knowledge, M. anisopliae is considered to be safe with minimal risks to vertebrates, humans and the environment.. metarhizium anisopliae| occurrence| host range| toxins| environmental fate| safety| side-effects|var. acridum deuteromycotina| ground-dwelling arthropods| beetle meligethes-aeneus| insect pathogenic fungi| mycotoxin destruxin-e| legume flower thrips| virus-like particles| beauveria-bassiana| entomogenous fungi| metarrhizium-anisopliae.	2007	metarhizium anisopliae| occurrence| host range| toxins| environmental fate| safety| side-effects|var. acridum deuteromycotina| ground-dwelling arthropods| beetle meligethes-aeneus| insect pathogenic fungi| mycotoxin destruxin-e| legume flower thrips| virus-like particles| beauveria-bassiana| entomogenous fungi| metarrhizium-anisopliae	Zimmermann, G	Review on safety of the entomopathogenic fungus Metarhizium anisopliae		BIOCONTROL SCIENCE AND TECHNOLOGY	Metarhizium anisopliae; occurrence; host range; toxins; environmental fate; safety; side-effects	VAR. ACRIDUM DEUTEROMYCOTINA; GROUND-DWELLING ARTHROPODS; BEETLE MELIGETHES-AENEUS; INSECT PATHOGENIC FUNGI; MYCOTOXIN DESTRUXIN-E; LEGUME FLOWER THRIPS; VIRUS-LIKE PARTICLES; BEAUVERIA-BASSIANA; ENTOMOGENOUS FUNGI; METARRHIZIUM-ANISOPLIAE	The entomopathogenic fungus Metarhizium anisopliae (Metschn.) Sorokin is widely used for biocontrol of pest insects, and many commercial products are on the market or under development. The aim of this review is to summarise all relevant safety data of this fungus, which are necessary for the commercialisation and registration process. The review contains the following sections: (1) identity, (2) biological properties (history, natural occurrence and geographical distribution, host range, mode of action, production of metabolites/toxins, effect of environmental factors), (3) methods to determine and quantify residues, (4) fate and behaviour in the environment (mobility and persistence in air, water and soil), (5) effects on non-target organisms (microorganisms, plants, soil organisms, aquatic organisms, predators, parasitoids, honey bees, earth worms, etc.), (6) effects on vertebrates (fish, amphibia, reptiles, and birds), and (7) effects on mammals and human health (allergy, pathogenicity/toxicity). On the basis of the presented knowledge, M. anisopliae is considered to be safe with minimal risks to vertebrates, humans and the environment.	257	135	2007	42	10.1080/09583150701593963	Biotechnology & Applied Microbiology; Entomology
Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism. The inherent resistance to diseases caused by Aspergillus fumigatus suggests the occurrence of regulatory mechanisms that provide the host with adequate defense without necessarily eliminating the fungus or causing unacceptable levels of host damage. In this study, we show that a division of labor occurs between functionally distinct regulatory T cells (Treg) that are coordinately activated by a CD28/B-7-dependent costimulatory pathway after exposure of mice to Aspergillus conidia. Early in infection, inflammation is controlled by the expansion, activation and local recruitment of CD4(+)CD25(+) Treg capable of suppressing neutrophils through the combined actions of IL-10 and CTLA-4 on indoleamine 2,3-dioxygenase. The levels of IFN-gamma produced in this early phase set the subsequent adaptive stage by conditioning the indoleamine 2,3-dioxygenase-dependent tolerogenic program of dendritic cells and the subsequent activation and expansion of tolerogenic Treg, which produce IL-10 and TGF-beta, inhibit Th2 cells, and prevent allergy to the fungus. The coordinate activation of Treg may, however, be subverted by the fungus, as germinating conidia are capable of interfering with anti-inflammatory and tolerogenic Treg programs. Thus, regulation is an essential component of the host response in infection and allergy to the fungus, and its manipulation may allow the pathogen to overcome host resistance and promote disease.. induced airway hyperreactivity| dendritic cells| indoleamine 2,3-dioxygenase| experimental asthma| candida-albicans| inhaled antigen| murine model| tgf-beta| in-vivo| fumigatus.	FEB 1-2006	induced airway hyperreactivity| dendritic cells| indoleamine 2,3-dioxygenase| experimental asthma| candida-albicans| inhaled antigen| murine model| tgf-beta| in-vivo| fumigatus	Montagnoli, C; Fallarino, F; Gaziano, R; Bozza, S; Bellocchio, S; Zelante, T; Kurup, WP; Pitzurra, L; Puccetti, P; Romani, L	Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism		JOURNAL OF IMMUNOLOGY		INDUCED AIRWAY HYPERREACTIVITY; DENDRITIC CELLS; INDOLEAMINE 2,3-DIOXYGENASE; EXPERIMENTAL ASTHMA; CANDIDA-ALBICANS; INHALED ANTIGEN; MURINE MODEL; TGF-BETA; IN-VIVO; FUMIGATUS	The inherent resistance to diseases caused by Aspergillus fumigatus suggests the occurrence of regulatory mechanisms that provide the host with adequate defense without necessarily eliminating the fungus or causing unacceptable levels of host damage. In this study, we show that a division of labor occurs between functionally distinct regulatory T cells (Treg) that are coordinately activated by a CD28/B-7-dependent costimulatory pathway after exposure of mice to Aspergillus conidia. Early in infection, inflammation is controlled by the expansion, activation and local recruitment of CD4(+)CD25(+) Treg capable of suppressing neutrophils through the combined actions of IL-10 and CTLA-4 on indoleamine 2,3-dioxygenase. The levels of IFN-gamma produced in this early phase set the subsequent adaptive stage by conditioning the indoleamine 2,3-dioxygenase-dependent tolerogenic program of dendritic cells and the subsequent activation and expansion of tolerogenic Treg, which produce IL-10 and TGF-beta, inhibit Th2 cells, and prevent allergy to the fungus. The coordinate activation of Treg may, however, be subverted by the fungus, as germinating conidia are capable of interfering with anti-inflammatory and tolerogenic Treg programs. Thus, regulation is an essential component of the host response in infection and allergy to the fungus, and its manipulation may allow the pathogen to overcome host resistance and promote disease.	52	135	2006	12		Immunology
Environmental routes for platinum group elements to biological materials - a review. The increased use of platinum group elements (PGE) in automobile catalysts has led to concern over potential environmental and biological accumulation. Platinum (Pt), palladium (Pd) and rhodium (Rh) concentrations have increased in the environment since the introduction of automobile catalysts. This review summarises current knowledge concerning the environmental mobility, speciation and bioavailability of Pt, Pd and Rh. The greater proportion of PGE emissions is from automobile catalysts, in the form of nanometer-sized catalyst particles, which deposit on roadside surfaces, as evidenced in samples of road dust, grass and soil. In soil, PGE can be transformed into more mobile species through complexation with organic matter and can be solubilised in low pH rainwater. There are indications that environmentally formed Pd species are more soluble and hence more mobile in the environment than Rh and Pt. PGE can reach waterbodies through stormwater transport and deposition in sediments. Besides external contamination of grass close to roads, internal PGE uptake has been observed for plants growing on soil contaminated with automobile catalyst PGE. Fine particles of PGE were also detected on the surface of feathers sampled from passerines and raptors in their natural habitat, and internal organs of these birds also contained PGE. Uptake has been observed in sediment-dwelling invertebrates, and laboratory studies have shown an uptake of PGE in eel and fish exposed to water containing road dust. The available evidence indicates that the PGE, especially Pd, are transported to biological materials through deposition in roots by binding to sulphur-rich low molecular weight species in plants. PGE uptake to exposed animals have uptake rates in the following order: Pd>Pt>Rh. The liver and kidney accumulate the highest levels of PGE, especially Pd. Urinary Pd and Rh, but not Pt, levels are correlated with traffic intensity. Dental alloys may lead to elevated urinary Pt levels. Platinum is a well-known allergen and Pd also shows a strong sensitisation potential. (C) 2004 Elsevier B.V. All rights reserved.. platinum| palladium| rhodium| pge| biological material| transformation| mobility| speciation| bioavailability| uptake|plasma-mass spectrometry| automobile catalytic-converters| magnetic-sector field| airborne particulate matter| size-exclusion chromatography| urban road dust| group-metals| icp-ms| contact-dermatitis| precious metals.	DEC 1-2004	platinum| palladium| rhodium| pge| biological material| transformation| mobility| speciation| bioavailability| uptake|plasma-mass spectrometry| automobile catalytic-converters| magnetic-sector field| airborne particulate matter| size-exclusion chromatography| urban road dust| group-metals| icp-ms| contact-dermatitis| precious metals	Ek, KH; Morrison, GM; Rauch, S	Environmental routes for platinum group elements to biological materials - a review		SCIENCE OF THE TOTAL ENVIRONMENT	platinum; palladium; rhodium; PGE; biological material; transformation; mobility; speciation; bioavailability; uptake	PLASMA-MASS SPECTROMETRY; AUTOMOBILE CATALYTIC-CONVERTERS; MAGNETIC-SECTOR FIELD; AIRBORNE PARTICULATE MATTER; SIZE-EXCLUSION CHROMATOGRAPHY; URBAN ROAD DUST; GROUP-METALS; ICP-MS; CONTACT-DERMATITIS; PRECIOUS METALS	The increased use of platinum group elements (PGE) in automobile catalysts has led to concern over potential environmental and biological accumulation. Platinum (Pt), palladium (Pd) and rhodium (Rh) concentrations have increased in the environment since the introduction of automobile catalysts. This review summarises current knowledge concerning the environmental mobility, speciation and bioavailability of Pt, Pd and Rh. The greater proportion of PGE emissions is from automobile catalysts, in the form of nanometer-sized catalyst particles, which deposit on roadside surfaces, as evidenced in samples of road dust, grass and soil. In soil, PGE can be transformed into more mobile species through complexation with organic matter and can be solubilised in low pH rainwater. There are indications that environmentally formed Pd species are more soluble and hence more mobile in the environment than Rh and Pt. PGE can reach waterbodies through stormwater transport and deposition in sediments. Besides external contamination of grass close to roads, internal PGE uptake has been observed for plants growing on soil contaminated with automobile catalyst PGE. Fine particles of PGE were also detected on the surface of feathers sampled from passerines and raptors in their natural habitat, and internal organs of these birds also contained PGE. Uptake has been observed in sediment-dwelling invertebrates, and laboratory studies have shown an uptake of PGE in eel and fish exposed to water containing road dust. The available evidence indicates that the PGE, especially Pd, are transported to biological materials through deposition in roots by binding to sulphur-rich low molecular weight species in plants. PGE uptake to exposed animals have uptake rates in the following order: Pd>Pt>Rh. The liver and kidney accumulate the highest levels of PGE, especially Pd. Urinary Pd and Rh, but not Pt, levels are correlated with traffic intensity. Dental alloys may lead to elevated urinary Pt levels. Platinum is a well-known allergen and Pd also shows a strong sensitisation potential. (C) 2004 Elsevier B.V. All rights reserved.	105	135	2004	18	10.1016/j.scitotenv.2004.04.027	Environmental Sciences & Ecology
Comparison between different traffic-related particle indicators: Elemental. carbon (EC), PM2.5 mass, and absorbance. Here we compare PM2.5 (particles with aerodynamic diameter less than 2.5 mum) mass and filter absorbance measurements with elemental carbon (EC) concentrations measured in parallel at the same site as well as collocated PM2.5 and PM10 (particles with aerodynamic diameter less than 10 mum) mass and absorbance measurements. The data were collected within the Traffic-Related Air Pollution on Childhood Asthma (TRAPCA) study in Germany, The Netherlands and Sweden. The study was designed to assess the health impact of spatial contrasts in long-term average concentrations. The measurement sites were distributed between background and traffic locations. Annual EC and PM2.5 absorbance measurements were at traffic sites on average 43-84% and 26-76% higher, respectively, compared to urban background sites. The contrast for PM2.5 mass measurements was lower (8-35%). The smaller contrast observed for PM2.5 mass in comparison with PM2.5 absorbance and EC documents that PM2.5 mass underestimates exposure contrasts related to motorized traffic emissions. The correlation between PM10 and PM2.5 was high, documenting that most of the spatial variation of PM10 was because of PM2.5. The measurement of PM2.5 absorbance was highly correlated with EC measurements and suggests that absorbance can be used as a simple, inexpensive and non-destructive method. to estimate motorized traffic-related particulate air pollution. The EC/absorbance relation differed between countries and site type (background/traffic), supporting the need for site-specific calibrations of the simple absorbance method. While the ratio between PM2.5 and PM10 mass ranged from 0.54 to 0.68, the ratio of PM2.5 absorbance and PM10 absorbance was 0.96-0.97, indicating that PM2.5 absorbance captures nearly all of the particle absorbance.. traffic-related pollutants| particles| pm10| pm2.5| absorbance| ec|chronic respiratory symptoms| diesel exhaust particles| particulate matter| air-pollution| spatial variability| daily mortality| children| health| smoke| pm10.	MAR-2003	traffic-related pollutants| particles| pm10| pm2.5| absorbance| ec|chronic respiratory symptoms| diesel exhaust particles| particulate matter| air-pollution| spatial variability| daily mortality| children| health| smoke| pm10	Cyrys, J; Heinrich, J; Hoek, G; Meliefste, K; Lewne, M; Gehring, U; Bellander, T; Fischer, P; Van Vliet, P; Brauer, M; Wichmann, HE; Brunekreef, B	Comparison between different traffic-related particle indicators: Elemental. carbon (EC), PM2.5 mass, and absorbance		JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY	traffic-related pollutants; particles; PM10; PM2.5; absorbance; EC	CHRONIC RESPIRATORY SYMPTOMS; DIESEL EXHAUST PARTICLES; PARTICULATE MATTER; AIR-POLLUTION; SPATIAL VARIABILITY; DAILY MORTALITY; CHILDREN; HEALTH; SMOKE; PM10	Here we compare PM2.5 (particles with aerodynamic diameter less than 2.5 mum) mass and filter absorbance measurements with elemental carbon (EC) concentrations measured in parallel at the same site as well as collocated PM2.5 and PM10 (particles with aerodynamic diameter less than 10 mum) mass and absorbance measurements. The data were collected within the Traffic-Related Air Pollution on Childhood Asthma (TRAPCA) study in Germany, The Netherlands and Sweden. The study was designed to assess the health impact of spatial contrasts in long-term average concentrations. The measurement sites were distributed between background and traffic locations. Annual EC and PM2.5 absorbance measurements were at traffic sites on average 43-84% and 26-76% higher, respectively, compared to urban background sites. The contrast for PM2.5 mass measurements was lower (8-35%). The smaller contrast observed for PM2.5 mass in comparison with PM2.5 absorbance and EC documents that PM2.5 mass underestimates exposure contrasts related to motorized traffic emissions. The correlation between PM10 and PM2.5 was high, documenting that most of the spatial variation of PM10 was because of PM2.5. The measurement of PM2.5 absorbance was highly correlated with EC measurements and suggests that absorbance can be used as a simple, inexpensive and non-destructive method. to estimate motorized traffic-related particulate air pollution. The EC/absorbance relation differed between countries and site type (background/traffic), supporting the need for site-specific calibrations of the simple absorbance method. While the ratio between PM2.5 and PM10 mass ranged from 0.54 to 0.68, the ratio of PM2.5 absorbance and PM10 absorbance was 0.96-0.97, indicating that PM2.5 absorbance captures nearly all of the particle absorbance.	43	135	2003	10	10.1038/sj.jea.7500262	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
MMP-2-and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Background: The course of asthma and chronic obstructive pulmonary disease (COPD) is associated with bronchial morphological changes. Metalloproteinases are thought to play a role in these structural changes. Methods: We studied the gelatinolytic activity present in the induced sputum from 20 patients with asthma, 20 with COPD and 19 healthy controls. The assessment of gelatinolytic activity was performed by quantitative zymography, and gelatinolytic species were identified by Western blot analysis. Tissue inhibitor of metalloproteinase-l (TIMP-1) was detected by reverse zymography and ELISA. Results: From zymography, we found significantly higher gelatinolytic activity linked to pro-matrix metalloproteinase-9 (pro-MMP-9) in the sputum from asthmatics (p < 0.0001) and COPD patients (p < 0.0001) compared to the control group. Furthermore, the activated form of MMP-9 (85 kD) was found in the sputum from 60% of asthmatics and 85% of COPD patients, but was absent in that of control subjects (p < 0.0001). Importantly, although less frequently detectable than pro-MMP-9, pro-MMP-2 (72 kD) was found more frequently in asthmatics (50%) than in control subjects (5%) (p < 0.005). We also described two unusual gelatinolytic species of 45 and 120 kD and showed that they derived from MMP-9 according to their ability to bind gelatin and anti-MMP-9 antibody. Levels of TIMP-1 were higher in asthmatics (p < 0.05) and COPD patients (p < 0.05) than in controls. Conclusion: Asthmatics and COPD patients display an increased gelatinolytic activity linked to MMP-2 and MMP-9 and higher levels of TIMP-1 in their sputum. Copyright (C) 2000 S. Karger AG, Basel.. asthma| copd| matrix metalloproteinases| mmp-9| timp-1|bronchoalveolar lavage fluid| air-flow obstruction| tissue inhibitor| iv collagenase| matrix metalloproteinases| alveolar macrophages| chronic-bronchitis| progelatinase-a| smooth-muscle| inflammation.	NOV-2000	asthma| copd| matrix metalloproteinases| mmp-9| timp-1|bronchoalveolar lavage fluid| air-flow obstruction| tissue inhibitor| iv collagenase| matrix metalloproteinases| alveolar macrophages| chronic-bronchitis| progelatinase-a| smooth-muscle| inflammation	Cataldo, D; Munaut, C; Noel, A; Frankenne, F; Bartsch, P; Foidart, JM; Louis, R	MMP-2-and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	asthma; COPD; matrix metalloproteinases; MMP-9; TIMP-1	BRONCHOALVEOLAR LAVAGE FLUID; AIR-FLOW OBSTRUCTION; TISSUE INHIBITOR; IV COLLAGENASE; MATRIX METALLOPROTEINASES; ALVEOLAR MACROPHAGES; CHRONIC-BRONCHITIS; PROGELATINASE-A; SMOOTH-MUSCLE; INFLAMMATION	Background: The course of asthma and chronic obstructive pulmonary disease (COPD) is associated with bronchial morphological changes. Metalloproteinases are thought to play a role in these structural changes. Methods: We studied the gelatinolytic activity present in the induced sputum from 20 patients with asthma, 20 with COPD and 19 healthy controls. The assessment of gelatinolytic activity was performed by quantitative zymography, and gelatinolytic species were identified by Western blot analysis. Tissue inhibitor of metalloproteinase-l (TIMP-1) was detected by reverse zymography and ELISA. Results: From zymography, we found significantly higher gelatinolytic activity linked to pro-matrix metalloproteinase-9 (pro-MMP-9) in the sputum from asthmatics (p < 0.0001) and COPD patients (p < 0.0001) compared to the control group. Furthermore, the activated form of MMP-9 (85 kD) was found in the sputum from 60% of asthmatics and 85% of COPD patients, but was absent in that of control subjects (p < 0.0001). Importantly, although less frequently detectable than pro-MMP-9, pro-MMP-2 (72 kD) was found more frequently in asthmatics (50%) than in control subjects (5%) (p < 0.005). We also described two unusual gelatinolytic species of 45 and 120 kD and showed that they derived from MMP-9 according to their ability to bind gelatin and anti-MMP-9 antibody. Levels of TIMP-1 were higher in asthmatics (p < 0.05) and COPD patients (p < 0.05) than in controls. Conclusion: Asthmatics and COPD patients display an increased gelatinolytic activity linked to MMP-2 and MMP-9 and higher levels of TIMP-1 in their sputum. Copyright (C) 2000 S. Karger AG, Basel.	36	135	2000	9	10.1159/000024452	Allergy; Immunology
Changes in the pattern of sensitization to common contact allergens in Denmark between 1985-86 and 1997-98, with a special view to the effect of preventive strategies. The objective of the present study is to describe any changes in the prevalence of sensitization to common contact allergens in patch-tested patients over a 12-year period, Attention is given to possible effects of preventive strategics introduced in Denmark regarding nickel and chromate sensitization during that period, and particular areas of concern are identified. Members of the Danish Contact Dermatitis Group collected patch-test results from consecutive eczema patients as well as information about exposures and demographic variables over a 6-month period in 1985-86. The investigation was repeated in 1997-98 in the same clinics, at the same time of year, using identical methods and patch-test substances, including nickel sulphate 5%, potassium dichromate 0.5% and fragrance mix 8%. Nickel was the most common contact allergen in both study periods, followed by the fragrance mix. In children 0-18 years of age, the frequency of nickel allergy decreased from 24.8% in the first study period to 9.2% in the second study period (P < 0.0008), Fragrance mix allergy doubled in frequency from 4.1% in 1985-86 to 9.9% in 1997-98, an increase that affected all age groups. Contact allergy to potassium dichromate decreased significantly from 3.0% in the first period to 1.2% in the second period (P = 0.001). The decrease was seen in both sexes and was most pronounced among those of working age, No other significant changes were found in the frequency of sensitization to common allergens over the 12-year observation period.. chromate| contact allergy| denmark| fragrance mix| nickel| patch testing|patch test| dermatitis| cement.	MAR-2000	chromate| contact allergy| denmark| fragrance mix| nickel| patch testing|patch test| dermatitis| cement	Johansen, JD; Menne, T; Christophersen, J; Kaaber, K; Veien, N	Changes in the pattern of sensitization to common contact allergens in Denmark between 1985-86 and 1997-98, with a special view to the effect of preventive strategies		BRITISH JOURNAL OF DERMATOLOGY	chromate; contact allergy; Denmark; fragrance mix; nickel; patch testing	PATCH TEST; DERMATITIS; CEMENT	The objective of the present study is to describe any changes in the prevalence of sensitization to common contact allergens in patch-tested patients over a 12-year period, Attention is given to possible effects of preventive strategics introduced in Denmark regarding nickel and chromate sensitization during that period, and particular areas of concern are identified. Members of the Danish Contact Dermatitis Group collected patch-test results from consecutive eczema patients as well as information about exposures and demographic variables over a 6-month period in 1985-86. The investigation was repeated in 1997-98 in the same clinics, at the same time of year, using identical methods and patch-test substances, including nickel sulphate 5%, potassium dichromate 0.5% and fragrance mix 8%. Nickel was the most common contact allergen in both study periods, followed by the fragrance mix. In children 0-18 years of age, the frequency of nickel allergy decreased from 24.8% in the first study period to 9.2% in the second study period (P < 0.0008), Fragrance mix allergy doubled in frequency from 4.1% in 1985-86 to 9.9% in 1997-98, an increase that affected all age groups. Contact allergy to potassium dichromate decreased significantly from 3.0% in the first period to 1.2% in the second period (P = 0.001). The decrease was seen in both sexes and was most pronounced among those of working age, No other significant changes were found in the frequency of sensitization to common allergens over the 12-year observation period.	21	135	2000	6	10.1046/j.1365-2133.2000.03362.x	Dermatology
Asthma exacerbations: Origin, effect, and prevention. Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children in the Western world. Despite advances in asthma management, acute exacerbations continue to occur and impose considerable morbidity on patients and constitute a major burden on health care resources. Respiratory tract viruses have emerged as the most frequent triggers for exacerbations in both children and adults; however, the mechanisms underlying these remain poorly understood. More recently, it has become increasingly clear that interactions might exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this article we begin with an overview of the health, economic, and social burden that exacerbations of asthma carry with them. This is followed by a review of the pathogenesis of asthma exacerbations, highlighting the various triggers responsible and multiple interactions that exist between them. The final section first addresses what preventative measures are currently available for asthma exacerbations and subsequently examines which of the new treatments in development might lessen the burden of exacerbations in the future. (J Allergy Clin Immunol 2011;128:1165-74.). asthma| asthma exacerbations| viral infection| virus| allergy| allergen| pollutant| bacteria|bronchial epithelial-cells| virus-induced asthma| budesonide/formoterol combination therapy| placebo-controlled trial| severe persistent asthma| indoor nitrogen-dioxide| severe allergic-asthma| necrosis-factor-alpha| inner-city children| human rhinovirus c.	DEC-2011	asthma| asthma exacerbations| viral infection| virus| allergy| allergen| pollutant| bacteria|bronchial epithelial-cells| virus-induced asthma| budesonide/formoterol combination therapy| placebo-controlled trial| severe persistent asthma| indoor nitrogen-dioxide| severe allergic-asthma| necrosis-factor-alpha| inner-city children| human rhinovirus c	Jackson, DJ; Sykes, A; Mallia, P; Johnston, SL	Asthma exacerbations: Origin, effect, and prevention		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Asthma; asthma exacerbations; viral infection; virus; allergy; allergen; pollutant; bacteria	BRONCHIAL EPITHELIAL-CELLS; VIRUS-INDUCED ASTHMA; BUDESONIDE/FORMOTEROL COMBINATION THERAPY; PLACEBO-CONTROLLED TRIAL; SEVERE PERSISTENT ASTHMA; INDOOR NITROGEN-DIOXIDE; SEVERE ALLERGIC-ASTHMA; NECROSIS-FACTOR-ALPHA; INNER-CITY CHILDREN; HUMAN RHINOVIRUS C	Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children in the Western world. Despite advances in asthma management, acute exacerbations continue to occur and impose considerable morbidity on patients and constitute a major burden on health care resources. Respiratory tract viruses have emerged as the most frequent triggers for exacerbations in both children and adults; however, the mechanisms underlying these remain poorly understood. More recently, it has become increasingly clear that interactions might exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this article we begin with an overview of the health, economic, and social burden that exacerbations of asthma carry with them. This is followed by a review of the pathogenesis of asthma exacerbations, highlighting the various triggers responsible and multiple interactions that exist between them. The final section first addresses what preventative measures are currently available for asthma exacerbations and subsequently examines which of the new treatments in development might lessen the burden of exacerbations in the future. (J Allergy Clin Immunol 2011;128:1165-74.)	136	134	2011	10	10.1016/j.jaci.2011.10.024	Allergy; Immunology
Animal models of asthma. Animal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma.. animal| asthma| model|allergen-induced airway| house-dust mite| antigen-induced bronchoconstriction| late-phase bronchoconstriction| respiratory system mechanics| brown-norway rat| mouse model| t-cells| bronchial responsiveness| lung inflammation.	JUL-2007	animal| asthma| model|allergen-induced airway| house-dust mite| antigen-induced bronchoconstriction| late-phase bronchoconstriction| respiratory system mechanics| brown-norway rat| mouse model| t-cells| bronchial responsiveness| lung inflammation	Zosky, GR; Sly, PD	Animal models of asthma		CLINICAL AND EXPERIMENTAL ALLERGY	animal; asthma; model	ALLERGEN-INDUCED AIRWAY; HOUSE-DUST MITE; ANTIGEN-INDUCED BRONCHOCONSTRICTION; LATE-PHASE BRONCHOCONSTRICTION; RESPIRATORY SYSTEM MECHANICS; BROWN-NORWAY RAT; MOUSE MODEL; T-CELLS; BRONCHIAL RESPONSIVENESS; LUNG INFLAMMATION	Animal models of asthma are a tool that allows studies to be conducted in the setting of an intact immune and respiratory system. These models have highlighted the importance of T-helper type 2 driven allergic responses in the progression of asthma and have been useful in the identification of potential drug targets for interventions involving allergic pathways. However, a number of drugs that have been shown to have some efficacy in animal models of asthma have shown little clinical benefit in human asthmatics. This may be due to a number of factors including the species of animal chosen and the methods used to induce an asthmatic phenotype in animals that do not normally develop a disease that could be characterized as asthma. The range of animal models available is vast, with the most popular models being rodents (inbred mice and rats) and guinea-pigs, which have the benefit of being easy to handle and being relatively cost effective compared with other models that are available. The recent advances in transgenic technology and the development of species-specific probes, particularly in mice, have allowed detailed mechanistic studies to be conducted. Despite these advances in technology, there are a number of issues with current animal models of asthma that must be recognized including the disparity in immunology and anatomy between these species and humans, the requirement for adjuvant during senitization in most models, the acute nature of the allergic response that is induced and the use of adult animals as the primary disease model. Some larger animal models using sheep and dogs have been developed that may address some of these issues but they also have different biology from humans in many ways and are extremely costly, with very few probes available for characterizing allergic responses in the airway in these species. As research in this area continues to expand, the relative merits and limitations of each model must be defined and understood in order to evaluate the information that is obtained from these models and to extrapolate these findings to humans so that effective drug therapies can be developed. Despite these issues, animal models have been, and will continue to be, vital in understanding the mechanisms that are involved in the development and progression of asthma.	154	134	2007	16	10.1111/j.1365-2222.2007.02740.x	Allergy; Immunology
"Evaluation of asthma with hyperpolarized helium-3 MRI - Correlation with clinical severity and spirometry. Background: Accurate characterization of asthma severity is difficult due to the variability of symptoms. Hyperpolarized helium-3 MRI ((HHeMR)-He-3) is a new technique in which the airspaces are visualized, depicting regions with airflow obstruction as ""ventilation defects."" The objective of this study was to compare the extent of (HHeMR)-He-3 ventilation defects with measures of asthma severity and spirometry. Methods: Patients with a physician diagnosis of asthma and normal control subjects underwent (HHeMR)-He-3. For each person, the number and size of ventilation defects were scored and the average number of ventilation defects per slice (VDS) was calculated. The correlations of the imaging findings with measures of asthma severity and spirometry were determined. Results: There were 58 patients with asthma (mild-intermittent, n = 13; mild-persistent, n = 13; moderate-persistent, n = 20; and severe-persistent, n = 12) and 18 control subjects. Mean +/- SE VDS for asthmatics was significantly greater than for control subjects (0.99 +/- 0.15 vs; 0.26 +/- 0.22, p = 0.004). Among asthmatics, VDS was significantly higher for the group with moderate-persistent and severe-persistent disease than for the group with mild-intermittent and mild-persistent disease (1.37 +/- 0.24 vs 0.53 +/- 0.12, p < 0.001). VDS correlated significantly with FEV1/FVC (r = -0.51, p = 0.002), forced expiratory flow between 25% and 75% from the beginning of FVC (FEF25-75%) percentage of predicted for height, sex, and race (%predicted) [r = -0.50, p = 0.001], and FEV1 %predicted (r = -0.40, p = 0.002), but not with FVC %predicted (r = -0.26, p = 0.057) and peak expiratory flow %predicted (r = -0.16, p = 0.231). Many asthmatics had an elevated VDS, but their spirometric indexes, except FEF25%-75%, were normal. Most ventilation defects were < 3 cm in size for all asthmatics. In the group of patients with moderate-to-severe persistant asthma, there were more defects >= 3 cm than in the group with mild-intermittent and mild-persistent disease (p = 0.021). Conclusions: Regional changes of airflow obstruction in asthmatics depicted by (HHeMR)-He-3 correlate with measures of asthma severity and spirometry.. airflow obstruction| airway| asthma| bronchial activity| hyperpolarized gases| hyperpolarized helium-3| mri| pulmonary function test| spirometry| ventilation defect|lung-transplant recipients| pulmonary-function tests| magnetic-resonance| cystic-fibrosis| small airways| air spaces| gas| abnormalities| ventilation| volumes."	OCT-2006	airflow obstruction| airway| asthma| bronchial activity| hyperpolarized gases| hyperpolarized helium-3| mri| pulmonary function test| spirometry| ventilation defect|lung-transplant recipients| pulmonary-function tests| magnetic-resonance| cystic-fibrosis| small airways| air spaces| gas| abnormalities| ventilation| volumes	de Lange, EE; Altes, TA; Patrie, JT; Gaare, JD; Knake, JJ; Mugler, JP; Platts-Mills, TA	Evaluation of asthma with hyperpolarized helium-3 MRI - Correlation with clinical severity and spirometry		CHEST	airflow obstruction; airway; asthma; bronchial activity; hyperpolarized gases; hyperpolarized helium-3; MRI; pulmonary function test; spirometry; ventilation defect	LUNG-TRANSPLANT RECIPIENTS; PULMONARY-FUNCTION TESTS; MAGNETIC-RESONANCE; CYSTIC-FIBROSIS; SMALL AIRWAYS; AIR SPACES; GAS; ABNORMALITIES; VENTILATION; VOLUMES	"Background: Accurate characterization of asthma severity is difficult due to the variability of symptoms. Hyperpolarized helium-3 MRI ((HHeMR)-He-3) is a new technique in which the airspaces are visualized, depicting regions with airflow obstruction as ""ventilation defects."" The objective of this study was to compare the extent of (HHeMR)-He-3 ventilation defects with measures of asthma severity and spirometry. Methods: Patients with a physician diagnosis of asthma and normal control subjects underwent (HHeMR)-He-3. For each person, the number and size of ventilation defects were scored and the average number of ventilation defects per slice (VDS) was calculated. The correlations of the imaging findings with measures of asthma severity and spirometry were determined. Results: There were 58 patients with asthma (mild-intermittent, n = 13; mild-persistent, n = 13; moderate-persistent, n = 20; and severe-persistent, n = 12) and 18 control subjects. Mean +/- SE VDS for asthmatics was significantly greater than for control subjects (0.99 +/- 0.15 vs; 0.26 +/- 0.22, p = 0.004). Among asthmatics, VDS was significantly higher for the group with moderate-persistent and severe-persistent disease than for the group with mild-intermittent and mild-persistent disease (1.37 +/- 0.24 vs 0.53 +/- 0.12, p < 0.001). VDS correlated significantly with FEV1/FVC (r = -0.51, p = 0.002), forced expiratory flow between 25% and 75% from the beginning of FVC (FEF25-75%) percentage of predicted for height, sex, and race (%predicted) [r = -0.50, p = 0.001], and FEV1 %predicted (r = -0.40, p = 0.002), but not with FVC %predicted (r = -0.26, p = 0.057) and peak expiratory flow %predicted (r = -0.16, p = 0.231). Many asthmatics had an elevated VDS, but their spirometric indexes, except FEF25%-75%, were normal. Most ventilation defects were < 3 cm in size for all asthmatics. In the group of patients with moderate-to-severe persistant asthma, there were more defects >= 3 cm than in the group with mild-intermittent and mild-persistent disease (p = 0.021). Conclusions: Regional changes of airflow obstruction in asthmatics depicted by (HHeMR)-He-3 correlate with measures of asthma severity and spirometry."	40	134	2006	8	10.1378/chest.130.4.1055	General & Internal Medicine; Respiratory System
"Parental report of health conditions and health care use among children with and without autism - National Survey of Children's Health. Objective: To compare parent-reported prevalence of health conditions and health care use between children with and without autism. Design: Cross-sectional analysis of the 2003 to 2004 National Survey of Children's Health. Setting: Population-based sample across the United States. Participants: More than 100 000 parents. The main exposure was ""autism"" (not further defined), from response to the question: ""Has a doctor or health professional ever told you that your child has autism?"" Main Outcome Measures: Medical and mental health conditions and measures of health care use. Results: Autism prevalence among children aged 3 to 17 years was 53 per 10 000 (95% confidence interval, 45-61 per 10 000), equating to a national estimate of 324 000 children (95% confidence interval, 274 000-375 000 children). Children with autism had a significantly (P <.001) higher prevalence of depression or anxiety problems (38.9% vs 4.2%) and behavioral or conduct problems (58.9% vs 5.2%) than children without autism. Respiratory, food, and skin allergies were reported by parents more often for children with autism, with food allergies having the strongest relative difference between the groups (odds ratio, 4.5; 95% confidence interval, 3.0-7.0). Children with autism had significantly (P <.001) higher mean physician visits over 12 months for preventive care, nonemergency care, and hospital emergency care, and were far more likely than children without autism to receive physical, occupational, or speech therapy (76.0% vs 6.3%), to need treatment or counseling for an emotional, developmental, or behavioral problem (75.4% vs 7.0%), and, among those taking a prescribed medication, to be using a medication long-term (51.4% vs 14.5%). Conclusion: We found markedly higher reports of concurrent conditions and health care use associated with childhood autism in this study.. spectrum disorders| gastrointestinal disorders| tuberous sclerosis| medical conditions| prevalence trends| asperger-syndrome| abnormalities| epilepsy| disabilities| individuals."	AUG-2006	spectrum disorders| gastrointestinal disorders| tuberous sclerosis| medical conditions| prevalence trends| asperger-syndrome| abnormalities| epilepsy| disabilities| individuals	Gurney, JG; McPheeters, ML; Davis, MM	Parental report of health conditions and health care use among children with and without autism - National Survey of Children's Health		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		SPECTRUM DISORDERS; GASTROINTESTINAL DISORDERS; TUBEROUS SCLEROSIS; MEDICAL CONDITIONS; PREVALENCE TRENDS; ASPERGER-SYNDROME; ABNORMALITIES; EPILEPSY; DISABILITIES; INDIVIDUALS	"Objective: To compare parent-reported prevalence of health conditions and health care use between children with and without autism. Design: Cross-sectional analysis of the 2003 to 2004 National Survey of Children's Health. Setting: Population-based sample across the United States. Participants: More than 100 000 parents. The main exposure was ""autism"" (not further defined), from response to the question: ""Has a doctor or health professional ever told you that your child has autism?"" Main Outcome Measures: Medical and mental health conditions and measures of health care use. Results: Autism prevalence among children aged 3 to 17 years was 53 per 10 000 (95% confidence interval, 45-61 per 10 000), equating to a national estimate of 324 000 children (95% confidence interval, 274 000-375 000 children). Children with autism had a significantly (P <.001) higher prevalence of depression or anxiety problems (38.9% vs 4.2%) and behavioral or conduct problems (58.9% vs 5.2%) than children without autism. Respiratory, food, and skin allergies were reported by parents more often for children with autism, with food allergies having the strongest relative difference between the groups (odds ratio, 4.5; 95% confidence interval, 3.0-7.0). Children with autism had significantly (P <.001) higher mean physician visits over 12 months for preventive care, nonemergency care, and hospital emergency care, and were far more likely than children without autism to receive physical, occupational, or speech therapy (76.0% vs 6.3%), to need treatment or counseling for an emotional, developmental, or behavioral problem (75.4% vs 7.0%), and, among those taking a prescribed medication, to be using a medication long-term (51.4% vs 14.5%). Conclusion: We found markedly higher reports of concurrent conditions and health care use associated with childhood autism in this study."	35	134	2006	6	10.1001/archpedi.160.8.825	Pediatrics
Anaphylactic and anaphylactoid reactions associated with lepirudin in patients with heparin-induced thrombocytopenia. Background - Lepirudin (Refludan) is a hirudin derivative. It is a direct thrombin inhibitor obtained by recombinant technology from the medicinal leech and is approved for treatment of heparin-induced thrombocytopenia complicated by thrombosis. Because 3 cases of fatal anaphylaxis possibly associated with use of lepirudin have been reported, we initiated an investigation of putative lepirudin-associated anaphylaxis. Methods and Results - Aided by the manufacturer (Schering AG, Berlin, Germany), we used the lepirudin study databases to identify all patients in whom possible anaphylaxis/severe allergy was recorded from 1994 to September 2002. The 26 possible cases identified were reviewed independently by 2 investigators. After excluding patients with mild skin reactions, reactions likely caused by concomitant medications, poorly documented cases, and reactions that did not correspond temporally with lepirudin use, there remained 9 patients judged to have had severe anaphylaxis in close temporal association with lepirudin. All reactions occurred within minutes of intravenous lepirudin administration, with 4 fatal outcomes (3 acute cardiorespiratory arrests, 1 hypotension-induced myocardial infarction). In these 4 cases, a previous uneventful treatment course with lepirudin was identified (1 to 12 weeks earlier). We recorded high-titer IgG-anti-lepirudin antibodies in an additional patient with anaphylaxis. Because lepirudin has been used in approximate to35 000 patients, the risk of anaphylaxis is approximate to0.015% (5 of 32 500) on first exposure and 0.16% (4 of 2500) in reexposed patients (7.5% estimated reexposures). Conclusion - Lepirudin can cause fatal anaphylaxis, particularly in patients who are treated within 3 months of a previous exposure. The overall risk/benefit assessment of lepirudin as a treatment for heparin-induced thrombocytopenia remains favorable.. hirudin| antibodies| anticoagulants| shock, anaphylactic|recombinant hirudin| antihirudin antibodies| clinical-relevance| r-hirudin| anticoagulation| ige.	OCT 28-2003	hirudin| antibodies| anticoagulants| shock, anaphylactic|recombinant hirudin| antihirudin antibodies| clinical-relevance| r-hirudin| anticoagulation| ige	Greinacher, A; Lubenow, N; Eichler, P	Anaphylactic and anaphylactoid reactions associated with lepirudin in patients with heparin-induced thrombocytopenia		CIRCULATION	hirudin; antibodies; anticoagulants; shock, anaphylactic	RECOMBINANT HIRUDIN; ANTIHIRUDIN ANTIBODIES; CLINICAL-RELEVANCE; R-HIRUDIN; ANTICOAGULATION; IGE	Background - Lepirudin (Refludan) is a hirudin derivative. It is a direct thrombin inhibitor obtained by recombinant technology from the medicinal leech and is approved for treatment of heparin-induced thrombocytopenia complicated by thrombosis. Because 3 cases of fatal anaphylaxis possibly associated with use of lepirudin have been reported, we initiated an investigation of putative lepirudin-associated anaphylaxis. Methods and Results - Aided by the manufacturer (Schering AG, Berlin, Germany), we used the lepirudin study databases to identify all patients in whom possible anaphylaxis/severe allergy was recorded from 1994 to September 2002. The 26 possible cases identified were reviewed independently by 2 investigators. After excluding patients with mild skin reactions, reactions likely caused by concomitant medications, poorly documented cases, and reactions that did not correspond temporally with lepirudin use, there remained 9 patients judged to have had severe anaphylaxis in close temporal association with lepirudin. All reactions occurred within minutes of intravenous lepirudin administration, with 4 fatal outcomes (3 acute cardiorespiratory arrests, 1 hypotension-induced myocardial infarction). In these 4 cases, a previous uneventful treatment course with lepirudin was identified (1 to 12 weeks earlier). We recorded high-titer IgG-anti-lepirudin antibodies in an additional patient with anaphylaxis. Because lepirudin has been used in approximate to35 000 patients, the risk of anaphylaxis is approximate to0.015% (5 of 32 500) on first exposure and 0.16% (4 of 2500) in reexposed patients (7.5% estimated reexposures). Conclusion - Lepirudin can cause fatal anaphylaxis, particularly in patients who are treated within 3 months of a previous exposure. The overall risk/benefit assessment of lepirudin as a treatment for heparin-induced thrombocytopenia remains favorable.	14	134	2003	4	10.1161/01.CIR.0000096056.37269.14	Cardiovascular System & Cardiology
Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Objective. Intranasal beclomethasone dipropionate (BDP) has generally been considered to have no systemic activity at recommended doses, but the potential for long-term effects on growth has not previously been evaluated. This study was undertaken to assess the effects of 1 year of treatment with intranasal BDP on growth in children. Study Design. In this double-blind, randomized, parallel- group study, 100 prepubertal children 6 to 9 years old with perennial allergic rhinitis were treated with aqueous BDP 168 mu g twice daily (n = 51) or placebo (n = 49) for 1 year. Subjects' baseline heights were required to be between the 5th and 95th percentile, and skeletal age as determined by left wrist radiograph was required to be within 2 years of chronological age. Washout periods for medications known to affect growth, including other forms of corticosteroids, were established, and these medications were prohibited during the study. However, short courses of oral prednisolone lasting no more than 7 days, and short courses of dermatologic corticosteroids lasting no more than 10 days, were allowed. Height was measured with a stadiometer after 1, 2, 4, 6, 8, 10, and 12 months of treatment. The hypothalamic-pituitary-adrenocortical axis was assessed by measurements of 8 AM basal cortisol concentrations and response to .25 mg cosyntropin stimulation. The primary safety parameter was the rate of change in standing height. Statistical analyses were based on all randomized subjects who received at least 1 dose of medication (intent-to-treat principle). The rate of change in standing height was analyzed for all subjects who entered the study and for those completing the full 12 months of treatment (n = 80). The rate of change in standing height over the 1-year study was calculated as the slope of a linear regression line fitted to each subject's height measurements over time. Because there was a statistically significant between-group difference in standing height at baseline, an analysis of covariance was performed for all analyses of standing height data. Results. Of the 100 subjects enrolled, 90 completed the study. The 2 treatment groups were generally comparable at baseline; however, at baseline, mean age and mean height were significantly greater in the BDP treatment group that the in placebo treatment group. In both analyses, overall growth rate was significantly slower in BDP-treated subjects than placebo-treated subjects. The mean change in standing height after 1 year was 5.0 cm in the BDP-treated subjects compared with 5.9 cm in the placebo-treated subjects. The difference in growth rates was evident as early as the 1-month treatment visit, suggesting that the effect on growth occurred initially. The growth-suppressive effect of BDP remained consistent across all age and gender subgroups, and among subjects with and without a previous history of corticosteroid use. Use of additional exogenous corticosteroids during the study was similar in both groups and did not affect the results. Because there was a baseline imbalance in height, a supplemental analysis of the differences in prestudy growth rates was performed. This analysis found no baseline imbalance in prestudy growth rates. To determine whether the difference in growth rates during the study could be attributed to preexisting growth rates, a z score analysis was performed. The heights of both groups were normalized at baseline and at the end of the study using the US National Center for Health Statistics data for mean and standard deviations of height. This analysis confirmed that the difference in growth rates between the 2 groups was primarily attributable to the treatment rather than to any preexisting difference in growth. Additional analyses confirmed that the results were not influenced by outlier values. No significant between-group difference were found in the hypothalamic-pituitary-adrenocortical axis assessments. No unusual adverse events were observed. No evidence of other systemic effects of BDP was found, including analysis for fluid and electrolyte imbalances; alterations in protein, lipid, or carbohydrate metabolism; alterations in formed elements in blood; and alterations in differential white blood cell counts, including eosinophils. Conclusions. Additional study is warranted to define the clinical relevance of these findings. This study suggests, however, that intranasal BDP may slow growth rate in children without suppressing basal 6 AM cortisol concentrations or the response to cosyntropin stimulation, which are commonly used clinically to test for adrenal suppression. The effect on final height is unknown. Alterative explantations for the finding of drug-induced growth suppression, including the possibility that the results were affected by either differences in height and age at baseline between the 2 groups or by outlier values, were discounted upon additional analysis. The results of this study were considered by the Food and Drug Administration in the development of recently proposed new class labeling for all inhaled and intranasal corticosteroids, which states that these agents may cause a reduction in growth velocity in pediatric patients (see reference 21). However, both the Food and Drug Administration and several professional bodies in the United States concur that, depending on disease severity, the benefits of intranasal corticosteroid therapy may outweigh the risks (see reference 22). Because the effect, if any, on final height in not known, the height of children receiving long-term therapy should be monitored periodically during treatment, and should be plotted on a growth or growth-velocity chart to monitor for growth suppression. To minimize the risks of systemic corticosteroid exposure, including growth suppresson, dose-reduction strategies should be considered. For patients who concomitantly receive exogenous corticosteroids via other routes for other conditions, such as inhaled corticosteroids for asthma, clinicians should consider the total corticosteroid exposure and titrate each patient to the lowest effective dose. Clinicians should also consider each medication's potential for systemic effects when selecting among the various available corticosteroids.. beclomethasone dipropionate| intranasal corticosteroids| growth| allergic rhinitis| pediatric|adrenal axis suppression| allergic rhinitis| therapeutic efficacy| prepubertal children| asthmatic-children| short-term| budesonide| glucocorticosteroids| corticosteroids| placebo.	FEB-2000	beclomethasone dipropionate| intranasal corticosteroids| growth| allergic rhinitis| pediatric|adrenal axis suppression| allergic rhinitis| therapeutic efficacy| prepubertal children| asthmatic-children| short-term| budesonide| glucocorticosteroids| corticosteroids| placebo	Skoner, DP; Rachelefsky, GS; Meltzer, EO; Chervinsky, P; Morris, RM; Seltzer, JM; Storms, WW; Wood, RA	Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate		PEDIATRICS	beclomethasone dipropionate; intranasal corticosteroids; growth; allergic rhinitis; pediatric	ADRENAL AXIS SUPPRESSION; ALLERGIC RHINITIS; THERAPEUTIC EFFICACY; PREPUBERTAL CHILDREN; ASTHMATIC-CHILDREN; SHORT-TERM; BUDESONIDE; GLUCOCORTICOSTEROIDS; CORTICOSTEROIDS; PLACEBO	Objective. Intranasal beclomethasone dipropionate (BDP) has generally been considered to have no systemic activity at recommended doses, but the potential for long-term effects on growth has not previously been evaluated. This study was undertaken to assess the effects of 1 year of treatment with intranasal BDP on growth in children. Study Design. In this double-blind, randomized, parallel- group study, 100 prepubertal children 6 to 9 years old with perennial allergic rhinitis were treated with aqueous BDP 168 mu g twice daily (n = 51) or placebo (n = 49) for 1 year. Subjects' baseline heights were required to be between the 5th and 95th percentile, and skeletal age as determined by left wrist radiograph was required to be within 2 years of chronological age. Washout periods for medications known to affect growth, including other forms of corticosteroids, were established, and these medications were prohibited during the study. However, short courses of oral prednisolone lasting no more than 7 days, and short courses of dermatologic corticosteroids lasting no more than 10 days, were allowed. Height was measured with a stadiometer after 1, 2, 4, 6, 8, 10, and 12 months of treatment. The hypothalamic-pituitary-adrenocortical axis was assessed by measurements of 8 AM basal cortisol concentrations and response to .25 mg cosyntropin stimulation. The primary safety parameter was the rate of change in standing height. Statistical analyses were based on all randomized subjects who received at least 1 dose of medication (intent-to-treat principle). The rate of change in standing height was analyzed for all subjects who entered the study and for those completing the full 12 months of treatment (n = 80). The rate of change in standing height over the 1-year study was calculated as the slope of a linear regression line fitted to each subject's height measurements over time. Because there was a statistically significant between-group difference in standing height at baseline, an analysis of covariance was performed for all analyses of standing height data. Results. Of the 100 subjects enrolled, 90 completed the study. The 2 treatment groups were generally comparable at baseline; however, at baseline, mean age and mean height were significantly greater in the BDP treatment group that the in placebo treatment group. In both analyses, overall growth rate was significantly slower in BDP-treated subjects than placebo-treated subjects. The mean change in standing height after 1 year was 5.0 cm in the BDP-treated subjects compared with 5.9 cm in the placebo-treated subjects. The difference in growth rates was evident as early as the 1-month treatment visit, suggesting that the effect on growth occurred initially. The growth-suppressive effect of BDP remained consistent across all age and gender subgroups, and among subjects with and without a previous history of corticosteroid use. Use of additional exogenous corticosteroids during the study was similar in both groups and did not affect the results. Because there was a baseline imbalance in height, a supplemental analysis of the differences in prestudy growth rates was performed. This analysis found no baseline imbalance in prestudy growth rates. To determine whether the difference in growth rates during the study could be attributed to preexisting growth rates, a z score analysis was performed. The heights of both groups were normalized at baseline and at the end of the study using the US National Center for Health Statistics data for mean and standard deviations of height. This analysis confirmed that the difference in growth rates between the 2 groups was primarily attributable to the treatment rather than to any preexisting difference in growth. Additional analyses confirmed that the results were not influenced by outlier values. No significant between-group difference were found in the hypothalamic-pituitary-adrenocortical axis assessments. No unusual adverse events were observed. No evidence of other systemic effects of BDP was found, including analysis for fluid and electrolyte imbalances; alterations in protein, lipid, or carbohydrate metabolism; alterations in formed elements in blood; and alterations in differential white blood cell counts, including eosinophils. Conclusions. Additional study is warranted to define the clinical relevance of these findings. This study suggests, however, that intranasal BDP may slow growth rate in children without suppressing basal 6 AM cortisol concentrations or the response to cosyntropin stimulation, which are commonly used clinically to test for adrenal suppression. The effect on final height is unknown. Alterative explantations for the finding of drug-induced growth suppression, including the possibility that the results were affected by either differences in height and age at baseline between the 2 groups or by outlier values, were discounted upon additional analysis. The results of this study were considered by the Food and Drug Administration in the development of recently proposed new class labeling for all inhaled and intranasal corticosteroids, which states that these agents may cause a reduction in growth velocity in pediatric patients (see reference 21). However, both the Food and Drug Administration and several professional bodies in the United States concur that, depending on disease severity, the benefits of intranasal corticosteroid therapy may outweigh the risks (see reference 22). Because the effect, if any, on final height in not known, the height of children receiving long-term therapy should be monitored periodically during treatment, and should be plotted on a growth or growth-velocity chart to monitor for growth suppression. To minimize the risks of systemic corticosteroid exposure, including growth suppresson, dose-reduction strategies should be considered. For patients who concomitantly receive exogenous corticosteroids via other routes for other conditions, such as inhaled corticosteroids for asthma, clinicians should consider the total corticosteroid exposure and titrate each patient to the lowest effective dose. Clinicians should also consider each medication's potential for systemic effects when selecting among the various available corticosteroids.	27	134	2000	7	10.1542/peds.105.2.e23	Pediatrics
Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation. Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 nonsevere asthma subjects from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. We partitioned airway obstruction into components of air trapping [indicated by forced vital capacity (FVC)] and airflow limitation [indicated by forced expiratory volume in 1 s (FEV1)/FVC]. Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV1/FVC. This pattern was confirmed with measures of residual lung volume/total lung capacity (TLC) in a subgroup. In contrast, nonsevere asthma did not exhibit prominent air trapping, even at FEV1/FVC <75% predicted. Air trapping also was associated with increases in TLC and functional reserve capacity. After maximal bronchodilation, FEV1 reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV1 after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV1 when baseline FEV1 was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.. airway closure| difficult asthma| fixed obstruction|chronic persistent asthma| elastic recoil| nocturnal asthma| flow obstruction| research-program| reference values| residual volume| expiratory flow| smooth-muscle| distal lung.	FEB-2008	airway closure| difficult asthma| fixed obstruction|chronic persistent asthma| elastic recoil| nocturnal asthma| flow obstruction| research-program| reference values| residual volume| expiratory flow| smooth-muscle| distal lung	Sorkness, RL; Bleecker, ER; Busse, WW; Calhoun, WJ; Castro, M; Chung, KF; Curran-Everett, D; Erzurum, SC; Gaston, BM; Israel, E; Jarjour, NN; Moore, WC; Peters, SP; Teague, WG; Wenzel, SE	Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation		JOURNAL OF APPLIED PHYSIOLOGY	airway closure; difficult asthma; fixed obstruction	CHRONIC PERSISTENT ASTHMA; ELASTIC RECOIL; NOCTURNAL ASTHMA; FLOW OBSTRUCTION; RESEARCH-PROGRAM; REFERENCE VALUES; RESIDUAL VOLUME; EXPIRATORY FLOW; SMOOTH-MUSCLE; DISTAL LUNG	Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 nonsevere asthma subjects from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. We partitioned airway obstruction into components of air trapping [indicated by forced vital capacity (FVC)] and airflow limitation [indicated by forced expiratory volume in 1 s (FEV1)/FVC]. Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV1/FVC. This pattern was confirmed with measures of residual lung volume/total lung capacity (TLC) in a subgroup. In contrast, nonsevere asthma did not exhibit prominent air trapping, even at FEV1/FVC <75% predicted. Air trapping also was associated with increases in TLC and functional reserve capacity. After maximal bronchodilation, FEV1 reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV1 after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV1 when baseline FEV1 was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.	51	133	2008	10	10.1152/japplphysiol.00329.2007	Physiology; Sport Sciences
Regional differences in EpiPen prescriptions in the United States: The potential role of vitamin D. Background: The epidemiology of anaphylaxis is uncertain, especially its geographic distribution. Objective: To address this deficit, we examined regional rates of EpiPen prescriptions in the United States. Methods: EpiPen prescriptions in 2004 were obtained for all 50 states and Washington, DC, from NDCHealth, Pharmaceutical Audit Suite (Alpharetta, Ga). Data included the number of total filled prescriptions, including refills, and the actual number of EpiPens prescribed. Several data sets were used to obtain state-specific populations, as well as multiple demographic, health, and weather characteristics. State population was used to calculate the average number of prescriptions written per person. Results: Overall, there were 1,511,534 EpiPen prescriptions filled during 2004. These prescriptions accounted for 2,495,188 EpiPens. On average, there were 5.71 EpiPens prescribed per 1000 persons. Massachusetts had the highest number of prescriptions per 1000 persons (11.8), whereas Hawaii had the lowest (2.7). In addition to state-to-state variation, there was an obvious regional difference: New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine) had the highest values, with 8 to 12 EpiPen prescriptions per 1000 persons, whereas the southern states (between and including California and Mississippi) had only 3 prescriptions per 1000 persons. The New England finding persisted even when controlling for all available factors (eg, population demographic characteristics, number of health care providers, prescriptions for other medications). Conclusion: A strong north-south gradient was observed for the prescription of EpiPens in the United States, with the highest rates found in New England. Clinical implications: The regional differences in EpiPen prescribing may provide important etiologic clues (vitamin D status) and merit further investigation.. anaphylaxis| epidemiology| epipen| vitamin d|regulatory t-cells| sun exposure| anaphylaxis| epidemiology| population| allergy| melanoma| children| risk| d-3.	JUL-2007	anaphylaxis| epidemiology| epipen| vitamin d|regulatory t-cells| sun exposure| anaphylaxis| epidemiology| population| allergy| melanoma| children| risk| d-3	Camargo, CA; Clark, S; Kaplan, MS; Lieberman, P; Wood, RA	Regional differences in EpiPen prescriptions in the United States: The potential role of vitamin D		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	anaphylaxis; epidemiology; EpiPen; vitamin D	REGULATORY T-CELLS; SUN EXPOSURE; ANAPHYLAXIS; EPIDEMIOLOGY; POPULATION; ALLERGY; MELANOMA; CHILDREN; RISK; D-3	Background: The epidemiology of anaphylaxis is uncertain, especially its geographic distribution. Objective: To address this deficit, we examined regional rates of EpiPen prescriptions in the United States. Methods: EpiPen prescriptions in 2004 were obtained for all 50 states and Washington, DC, from NDCHealth, Pharmaceutical Audit Suite (Alpharetta, Ga). Data included the number of total filled prescriptions, including refills, and the actual number of EpiPens prescribed. Several data sets were used to obtain state-specific populations, as well as multiple demographic, health, and weather characteristics. State population was used to calculate the average number of prescriptions written per person. Results: Overall, there were 1,511,534 EpiPen prescriptions filled during 2004. These prescriptions accounted for 2,495,188 EpiPens. On average, there were 5.71 EpiPens prescribed per 1000 persons. Massachusetts had the highest number of prescriptions per 1000 persons (11.8), whereas Hawaii had the lowest (2.7). In addition to state-to-state variation, there was an obvious regional difference: New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine) had the highest values, with 8 to 12 EpiPen prescriptions per 1000 persons, whereas the southern states (between and including California and Mississippi) had only 3 prescriptions per 1000 persons. The New England finding persisted even when controlling for all available factors (eg, population demographic characteristics, number of health care providers, prescriptions for other medications). Conclusion: A strong north-south gradient was observed for the prescription of EpiPens in the United States, with the highest rates found in New England. Clinical implications: The regional differences in EpiPen prescribing may provide important etiologic clues (vitamin D status) and merit further investigation.	29	133	2007	6	10.1016/j.jaci.2007.03.049	Allergy; Immunology
Increased risk of childhood asthma from antibiotic use in early life. Background: To address the major methodological issues of reverse causation and selection bias in epidemiologic studies of antibiotic use in early life and the development of asthma, we undertook a cohort study of this association in a complete population of children. Methods: Using the health-care and prescription databases of Manitoba, Canada, this longitudinal study assessed the association between antibiotic prescription use during the first year of life and asthma at age 7 years in a 1995 birth cohort of 13,116 children. Results: Independent of well-known asthma risk factors, asthma was significantly more likely to develop in children who had received antibiotics in the first year of life at age 7 years. The association with asthma was observed for antibiotic use in non-respiratory tract infections (adjusted odds ratio [OR], 1.86; 95% confidence interval [CI], 1.02 to 3.37). The risk of asthma was highest in children receiving more than four courses of antibiotics (adjusted OR, 1.46; 95% CI, 1.14 to 1.88), especially among rural children, and in the absence of maternal asthma or a dog in the birth year. Broad-spectrum (BS) cephalosporin use was more common in these sub-populations of children. Conclusions: Antibiotic use in early life was associated with the development of childhood asthma, a risk that may be reduced by avoiding the use of BS cephalosporins.. antibacterial agents| asthma| child| infant|intestinal microflora| atopic-dermatitis| 1st year| allergic disease| oral antibiotics| swedish infants| birth cohort| school-age| children| exposure.	JUN-2007	antibacterial agents| asthma| child| infant|intestinal microflora| atopic-dermatitis| 1st year| allergic disease| oral antibiotics| swedish infants| birth cohort| school-age| children| exposure	Kozyrskyj, AL; Ernst, P; Becker, AB	Increased risk of childhood asthma from antibiotic use in early life		CHEST	antibacterial agents; asthma; child; infant	INTESTINAL MICROFLORA; ATOPIC-DERMATITIS; 1ST YEAR; ALLERGIC DISEASE; ORAL ANTIBIOTICS; SWEDISH INFANTS; BIRTH COHORT; SCHOOL-AGE; CHILDREN; EXPOSURE	Background: To address the major methodological issues of reverse causation and selection bias in epidemiologic studies of antibiotic use in early life and the development of asthma, we undertook a cohort study of this association in a complete population of children. Methods: Using the health-care and prescription databases of Manitoba, Canada, this longitudinal study assessed the association between antibiotic prescription use during the first year of life and asthma at age 7 years in a 1995 birth cohort of 13,116 children. Results: Independent of well-known asthma risk factors, asthma was significantly more likely to develop in children who had received antibiotics in the first year of life at age 7 years. The association with asthma was observed for antibiotic use in non-respiratory tract infections (adjusted odds ratio [OR], 1.86; 95% confidence interval [CI], 1.02 to 3.37). The risk of asthma was highest in children receiving more than four courses of antibiotics (adjusted OR, 1.46; 95% CI, 1.14 to 1.88), especially among rural children, and in the absence of maternal asthma or a dog in the birth year. Broad-spectrum (BS) cephalosporin use was more common in these sub-populations of children. Conclusions: Antibiotic use in early life was associated with the development of childhood asthma, a risk that may be reduced by avoiding the use of BS cephalosporins.	50	133	2007	7	10.1378/chest.06-3008	General & Internal Medicine; Respiratory System
Allergies, infections and the hygiene hypothesis - The epidemiological evidence. The 'hygiene hypothesis' was first proposed by Strachan in 1989 suggesting that infections and unhygienic contact with older siblings or through other exposures may confer protection from the development of allergic illnesses. This hypothesis has evolved in various ways exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and their effect on underlying responses of innate and adaptive immunity. So far a truly unifying concept is still lacking, but various pieces of a complex interplay between a host's immune response, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures become apparent. All these pieces eventually assemble to the clinical presentation of a complex syndrome namely of asthma and allergic illnesses. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future based on the concepts of the 'hygiene hypothesis'. (C) 2007 Elsevier GmbH. All rights reserved.. hygiene hypothesis| epidemiology| allergy| infection|early bcg vaccination| school-age-children| day-care attendance| atopic disease| birth cohort| early-life| farmers children| early-childhood| hay-fever| 1st year.	2007	hygiene hypothesis| epidemiology| allergy| infection|early bcg vaccination| school-age-children| day-care attendance| atopic disease| birth cohort| early-life| farmers children| early-childhood| hay-fever| 1st year	von Mutius, E	Allergies, infections and the hygiene hypothesis - The epidemiological evidence		IMMUNOBIOLOGY	hygiene hypothesis; epidemiology; allergy; infection	EARLY BCG VACCINATION; SCHOOL-AGE-CHILDREN; DAY-CARE ATTENDANCE; ATOPIC DISEASE; BIRTH COHORT; EARLY-LIFE; FARMERS CHILDREN; EARLY-CHILDHOOD; HAY-FEVER; 1ST YEAR	The 'hygiene hypothesis' was first proposed by Strachan in 1989 suggesting that infections and unhygienic contact with older siblings or through other exposures may confer protection from the development of allergic illnesses. This hypothesis has evolved in various ways exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and their effect on underlying responses of innate and adaptive immunity. So far a truly unifying concept is still lacking, but various pieces of a complex interplay between a host's immune response, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures become apparent. All these pieces eventually assemble to the clinical presentation of a complex syndrome namely of asthma and allergic illnesses. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future based on the concepts of the 'hygiene hypothesis'. (C) 2007 Elsevier GmbH. All rights reserved.	48	133	2007	7	10.1016/j.imbio.2007.03.002	Immunology
Do farming exposures cause or prevent asthma? Results from a study of adult Norwegian farmers. Background: A protective effect of endotoxin exposure on atopy and asthma in farmers' children has been postulated. Studies of adult farmers have shown conflicting results but often lack exposure data. The prevalence of asthma in farmers with different exposure levels to microbial agents and irritant gases was compared. Methods: Atopy was defined as a positive response to multiple radioallergosorbent tests (RAST) with a panel of 10 common respiratory allergens, and asthma was ascertained by a questionnaire using a stratified sample (n = 2169) of a farming population from south-eastern Norway. Exposure of farmers to total dust, fungal spores, bacteria, endotoxins, and ammonia was assessed by exposure measurements. Results: The prevalence of asthma was 3.7% for physician diagnosed asthma and 2.7% for current asthma. The prevalence of atopy was 14%, but most asthmatic subjects were non-atopic (80%). Compared with farmers without livestock, ( 1) asthma was significantly higher in cattle farmers (ORadj 1.8, 95% CI 1.1 to 2.8) and pig farmers (ORadj 1.6, 95% CI 1.0 to 2.5), (2) non-atopic asthma was significantly higher in pig farmers (ORadj 2.0, 95% CI 1.2 to 3.3) and in farmers with two or more types of livestock (ORadj 1.9, 95% CI 1.1 to 3.3), and ( 3) atopic asthma was less common in farmers with two or more types of livestock (ORadj 0.32, 95% CI 0.11 to 0.97). Exposure to endotoxins, fungal spores, and ammonia was positively associated with non-atopic asthma and negatively associated with atopic asthma. No associations were found with atopy. Conclusions: Exposure to endotoxins and fungal spores appears to have a protective effect on atopic asthma but may induce non-atopic asthma in farmers.. respiratory symptoms| danish farmers| hay-fever| allergic sensitization| occupational exposure| chronic-bronchitis| children| prevalence| endotoxin| dust.	MAY 1-2004	respiratory symptoms| danish farmers| hay-fever| allergic sensitization| occupational exposure| chronic-bronchitis| children| prevalence| endotoxin| dust	Eduard, W; Douwes, J; Omenaas, E; Heederik, D	Do farming exposures cause or prevent asthma? Results from a study of adult Norwegian farmers		THORAX		RESPIRATORY SYMPTOMS; DANISH FARMERS; HAY-FEVER; ALLERGIC SENSITIZATION; OCCUPATIONAL EXPOSURE; CHRONIC-BRONCHITIS; CHILDREN; PREVALENCE; ENDOTOXIN; DUST	Background: A protective effect of endotoxin exposure on atopy and asthma in farmers' children has been postulated. Studies of adult farmers have shown conflicting results but often lack exposure data. The prevalence of asthma in farmers with different exposure levels to microbial agents and irritant gases was compared. Methods: Atopy was defined as a positive response to multiple radioallergosorbent tests (RAST) with a panel of 10 common respiratory allergens, and asthma was ascertained by a questionnaire using a stratified sample (n = 2169) of a farming population from south-eastern Norway. Exposure of farmers to total dust, fungal spores, bacteria, endotoxins, and ammonia was assessed by exposure measurements. Results: The prevalence of asthma was 3.7% for physician diagnosed asthma and 2.7% for current asthma. The prevalence of atopy was 14%, but most asthmatic subjects were non-atopic (80%). Compared with farmers without livestock, ( 1) asthma was significantly higher in cattle farmers (ORadj 1.8, 95% CI 1.1 to 2.8) and pig farmers (ORadj 1.6, 95% CI 1.0 to 2.5), (2) non-atopic asthma was significantly higher in pig farmers (ORadj 2.0, 95% CI 1.2 to 3.3) and in farmers with two or more types of livestock (ORadj 1.9, 95% CI 1.1 to 3.3), and ( 3) atopic asthma was less common in farmers with two or more types of livestock (ORadj 0.32, 95% CI 0.11 to 0.97). Exposure to endotoxins, fungal spores, and ammonia was positively associated with non-atopic asthma and negatively associated with atopic asthma. No associations were found with atopy. Conclusions: Exposure to endotoxins and fungal spores appears to have a protective effect on atopic asthma but may induce non-atopic asthma in farmers.	33	133	2004	6	10.1136/thx.2004.013326	Respiratory System
Bronchiolar disorders. Bronchiolar abnormalities are relatively common and occur in a variety of clinical settings. Various histopathologic patterns of bronchiolar injury have been described and have led to confusing nomenclature with redundant and overlapping terms. Some histopathologic patterns of bronchiolar disease may be relatively unique to a specific clinical context but others are nonspecific with respect to either etiology or pathogenesis. Herein, we present a scheme separating (1) those disorders in which the bronchiolar disease is the predominant abnormality (primary bronchiolar disorders) from (2) parenchymal disorders with prominent bronchiolar involvement and (3) bronchiolar involvement in large airway diseases. Primary bronchiolar disorders include constrictive bronchiolitis (obliterative bronchiolitis, bronchiolitis obliterans), acute bronchiolitis, diffuse panbronchiolitis, respiratory bronchiolitis, mineral dust airway disease, follicular bronchiolitis, and a few other rare variants. Prominent bronchiolar involvement may be seen in several interstitial lung diseases, including hypersensitivity pneumonitis, respiratory bronchiolitis-associated interstitial lung disease, cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia), and pulmonary Langerhans' cell histiocytosis. Large airway diseases that commonly involve bronchioles include bronchiectasis, asthma, and chronic obstructive pulmonary disease. The clinical relevance of a bronchiolar lesion is best determined by identifying the underlying histopathologic pattern and assessing the correlative clinico-physiologic-radiologic context.. bronchiolitis| bronchiolitis obliterans| organizing pneumonia|interstitial lung-disease| obliterans organizing pneumonia| high-resolution ct| langerhans-cell histiocytosis| idiopathic pulmonary fibrosis| respiratory syncytial virus| small airways diseases| air-flow obstruction| thin-section ct| diffuse panbronchiolitis.	DEC 1-2003	bronchiolitis| bronchiolitis obliterans| organizing pneumonia|interstitial lung-disease| obliterans organizing pneumonia| high-resolution ct| langerhans-cell histiocytosis| idiopathic pulmonary fibrosis| respiratory syncytial virus| small airways diseases| air-flow obstruction| thin-section ct| diffuse panbronchiolitis	Ryu, JH; Myers, J; Swenson, SJ	Bronchiolar disorders		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	bronchiolitis; bronchiolitis obliterans; organizing pneumonia	INTERSTITIAL LUNG-DISEASE; OBLITERANS ORGANIZING PNEUMONIA; HIGH-RESOLUTION CT; LANGERHANS-CELL HISTIOCYTOSIS; IDIOPATHIC PULMONARY FIBROSIS; RESPIRATORY SYNCYTIAL VIRUS; SMALL AIRWAYS DISEASES; AIR-FLOW OBSTRUCTION; THIN-SECTION CT; DIFFUSE PANBRONCHIOLITIS	Bronchiolar abnormalities are relatively common and occur in a variety of clinical settings. Various histopathologic patterns of bronchiolar injury have been described and have led to confusing nomenclature with redundant and overlapping terms. Some histopathologic patterns of bronchiolar disease may be relatively unique to a specific clinical context but others are nonspecific with respect to either etiology or pathogenesis. Herein, we present a scheme separating (1) those disorders in which the bronchiolar disease is the predominant abnormality (primary bronchiolar disorders) from (2) parenchymal disorders with prominent bronchiolar involvement and (3) bronchiolar involvement in large airway diseases. Primary bronchiolar disorders include constrictive bronchiolitis (obliterative bronchiolitis, bronchiolitis obliterans), acute bronchiolitis, diffuse panbronchiolitis, respiratory bronchiolitis, mineral dust airway disease, follicular bronchiolitis, and a few other rare variants. Prominent bronchiolar involvement may be seen in several interstitial lung diseases, including hypersensitivity pneumonitis, respiratory bronchiolitis-associated interstitial lung disease, cryptogenic organizing pneumonia (idiopathic bronchiolitis obliterans organizing pneumonia), and pulmonary Langerhans' cell histiocytosis. Large airway diseases that commonly involve bronchioles include bronchiectasis, asthma, and chronic obstructive pulmonary disease. The clinical relevance of a bronchiolar lesion is best determined by identifying the underlying histopathologic pattern and assessing the correlative clinico-physiologic-radiologic context.	164	133	2003	16	10.1164/rccm.200301.053SO	General & Internal Medicine; Respiratory System
Ambient nitrogen dioxide and distance from a major highway. The primary objective of this pilot study was to measure the variation of ambient nitrogen dioxide (NO2) concentration with increasing distance from a major highway in Montreal, Canada, in order to assess the validity of distance from the roadways as a surrogate for exposure to traffic-related air pollution in epidemiologic studies. A total of 31 two-sided Ogawa(TM) passive samplers (using triethanolamine-impregnated filters as an absorbent) were installed for 7 days in groups of two or three along an axis perpendicular to a major highway where traffic density exceeds 100 000 vehicles/day. Distances ranged from 0 to 1310 m from the highway. Concentrations of NO2 ranged from 11.9 to 29.3 ppb, and decreased significantly with increasing logarithmic distance from the highway (P < 0.0001). Concentrations of NO2 were also significantly lower upwind than downwind relative to the highway (P= 0.0012). These findings indicate that distance from highways may be a valid surrogate for traffic-related air pollution. (C) 2003 Elsevier Science B.V. All rights reserved.. air pollution| nitrogen dioxide| no2| passive monitoring| traffic|air-pollution| asthma| motorways.	AUG 1-2003	air pollution| nitrogen dioxide| no2| passive monitoring| traffic|air-pollution| asthma| motorways	Gilbert, NL; Woodhouse, S; Stieb, DM; Brook, JR	Ambient nitrogen dioxide and distance from a major highway		SCIENCE OF THE TOTAL ENVIRONMENT	air pollution; nitrogen dioxide; NO2; passive monitoring; traffic	AIR-POLLUTION; ASTHMA; MOTORWAYS	The primary objective of this pilot study was to measure the variation of ambient nitrogen dioxide (NO2) concentration with increasing distance from a major highway in Montreal, Canada, in order to assess the validity of distance from the roadways as a surrogate for exposure to traffic-related air pollution in epidemiologic studies. A total of 31 two-sided Ogawa(TM) passive samplers (using triethanolamine-impregnated filters as an absorbent) were installed for 7 days in groups of two or three along an axis perpendicular to a major highway where traffic density exceeds 100 000 vehicles/day. Distances ranged from 0 to 1310 m from the highway. Concentrations of NO2 ranged from 11.9 to 29.3 ppb, and decreased significantly with increasing logarithmic distance from the highway (P < 0.0001). Concentrations of NO2 were also significantly lower upwind than downwind relative to the highway (P= 0.0012). These findings indicate that distance from highways may be a valid surrogate for traffic-related air pollution. (C) 2003 Elsevier Science B.V. All rights reserved.	14	133	2003	4	10.1016/S0048-9697(03)00228-6	Environmental Sciences & Ecology
Spatial variability of fine particle concentrations in three European areas. Epidemiological studies of long-term air pollution effects have been hampered by difficulties in characterizing the spatial variation in air pollution. We conducted a study to assess the risk of long-term exposure to traffic-related air pollution for the development of inhalant allergy and asthma in children in Stockholm county, Munich and the Netherlands. Exposure to traffic-related air pollution was assessed through a 1-year monitoring program and regression modeling using exposure indicators. This paper documents the performance of the exposure monitoring strategy and the spatial variation of ambient particle concentrations. We measured the ambient concentration of PM2.5 and the reflectance of PM2.5 filters ('soot') at 40-42 sites representative of different exposure conditions of the three study populations. Each site was measured during four 14-day average sampling periods spread over one year (spring 1999 to summer 2000). In each study area, a continuous measurement site was operated to remove potential bias due to temporal variation. The selected approach was an efficient method to characterize spatial differences in annual average concentration between a large number of sites in each study area. Adjustment with data from the continuous measurement site improved the precision of the calculated annual averages, especially for PM2.5. Annual average PM2.5 concentrations ranged from 11 to 20 mug/m(3) in Munich, from 8 to 16 mug/m(3) in Stockholm and from 14 to 26 mug/m(3) in the Netherlands. Larger spatial contrasts were found for the absorption coefficient of PM2.5. PM2.5 concentrations were on average 17-18% higher at traffic sites than at urban background sites, but PM2.5 absorption coefficients at traffic sites were between 31% and 55% increased above background. This suggests that spatial variation of traffic-related air pollution may be underestimated if PM2.5 only is measured. (C) 2002 Elsevier Science Ltd. All rights reserved.. pm2.5| diesel| soot| traffic| exposure|urban air-pollution| particulate matter| nitrogen-dioxide| black smoke| rural sites| exposure| children| indoor| pm10| netherlands.	SEP-2002	pm2.5| diesel| soot| traffic| exposure|urban air-pollution| particulate matter| nitrogen-dioxide| black smoke| rural sites| exposure| children| indoor| pm10| netherlands	Hoek, G; Meliefste, K; Cyrys, J; Lewne, M; Bellander, T; Brauer, M; Fischer, P; Gehring, U; Heinrich, J; van Vliet, P; Brunekreef, B	Spatial variability of fine particle concentrations in three European areas		ATMOSPHERIC ENVIRONMENT	PM2.5; diesel; soot; traffic; exposure	URBAN AIR-POLLUTION; PARTICULATE MATTER; NITROGEN-DIOXIDE; BLACK SMOKE; RURAL SITES; EXPOSURE; CHILDREN; INDOOR; PM10; NETHERLANDS	Epidemiological studies of long-term air pollution effects have been hampered by difficulties in characterizing the spatial variation in air pollution. We conducted a study to assess the risk of long-term exposure to traffic-related air pollution for the development of inhalant allergy and asthma in children in Stockholm county, Munich and the Netherlands. Exposure to traffic-related air pollution was assessed through a 1-year monitoring program and regression modeling using exposure indicators. This paper documents the performance of the exposure monitoring strategy and the spatial variation of ambient particle concentrations. We measured the ambient concentration of PM2.5 and the reflectance of PM2.5 filters ('soot') at 40-42 sites representative of different exposure conditions of the three study populations. Each site was measured during four 14-day average sampling periods spread over one year (spring 1999 to summer 2000). In each study area, a continuous measurement site was operated to remove potential bias due to temporal variation. The selected approach was an efficient method to characterize spatial differences in annual average concentration between a large number of sites in each study area. Adjustment with data from the continuous measurement site improved the precision of the calculated annual averages, especially for PM2.5. Annual average PM2.5 concentrations ranged from 11 to 20 mug/m(3) in Munich, from 8 to 16 mug/m(3) in Stockholm and from 14 to 26 mug/m(3) in the Netherlands. Larger spatial contrasts were found for the absorption coefficient of PM2.5. PM2.5 concentrations were on average 17-18% higher at traffic sites than at urban background sites, but PM2.5 absorption coefficients at traffic sites were between 31% and 55% increased above background. This suggests that spatial variation of traffic-related air pollution may be underestimated if PM2.5 only is measured. (C) 2002 Elsevier Science Ltd. All rights reserved.	28	133	2002	12	10.1016/S1352-2310(02)00297-2	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Diesel exhaust and asthma: Hypotheses and molecular mechanisms of action. Several components of air pollution have been linked to asthma. In addition to the well-studied critera air pollutants, such as nitrogen dioxide, sulfur dioxide, and ozone, diesel exhaust and diesel exhaust particles (DEPs) also appear to play a role in respiratory and allergic diseases. Diesel exhaust is composed of vapors, gases, and fine particles emitted by diesel-fueled compression-ignition engines. DEPs can act as nonspecific airway irritants at relatively high levels. At lower levels, DEPs promote release of specific cytokines, chemokines, immunoglobulins, and oxidants in the upper and lower airway. Release of these mediators of the allergic and inflammatory response initiates a cascade that can culminate in airway inflammation, mucus secretion, serum leakage into the air-ways, and bronchial smooth muscle contraction. DEPs also may promote expression of the T(H)2 immunologic response phenotype that has been associated with asthma and allergic disease. DEPs appear to have greater immunologic effects in the presence of environmental allergens than they do a-lone. This immunologic evidence may help explain the epidemiologic studies indicating that children living along major trucking thoroughfares are at increased risk for asthmatic and allergic symptoms and a-re more likely to have objective evidence of respiratory dysfunction.. air pollution| allergy| asthma| diesel exhaust| immunology| irritant| particulate matter| respiratory|bronchial epithelial-cells| particulate air-pollution| ige antibody-production| emergency room visits| short-term exposure| activity in-vitro| adjuvant activity| cytokine production| childhood asthma| nitrogen-dioxide.	FEB-2002	air pollution| allergy| asthma| diesel exhaust| immunology| irritant| particulate matter| respiratory|bronchial epithelial-cells| particulate air-pollution| ige antibody-production| emergency room visits| short-term exposure| activity in-vitro| adjuvant activity| cytokine production| childhood asthma| nitrogen-dioxide	Pandya, RJ; Solomon, G; Kinner, A; Balmes, JR	Diesel exhaust and asthma: Hypotheses and molecular mechanisms of action		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; allergy; asthma; diesel exhaust; immunology; irritant; particulate matter; respiratory	BRONCHIAL EPITHELIAL-CELLS; PARTICULATE AIR-POLLUTION; IGE ANTIBODY-PRODUCTION; EMERGENCY ROOM VISITS; SHORT-TERM EXPOSURE; ACTIVITY IN-VITRO; ADJUVANT ACTIVITY; CYTOKINE PRODUCTION; CHILDHOOD ASTHMA; NITROGEN-DIOXIDE	Several components of air pollution have been linked to asthma. In addition to the well-studied critera air pollutants, such as nitrogen dioxide, sulfur dioxide, and ozone, diesel exhaust and diesel exhaust particles (DEPs) also appear to play a role in respiratory and allergic diseases. Diesel exhaust is composed of vapors, gases, and fine particles emitted by diesel-fueled compression-ignition engines. DEPs can act as nonspecific airway irritants at relatively high levels. At lower levels, DEPs promote release of specific cytokines, chemokines, immunoglobulins, and oxidants in the upper and lower airway. Release of these mediators of the allergic and inflammatory response initiates a cascade that can culminate in airway inflammation, mucus secretion, serum leakage into the air-ways, and bronchial smooth muscle contraction. DEPs also may promote expression of the T(H)2 immunologic response phenotype that has been associated with asthma and allergic disease. DEPs appear to have greater immunologic effects in the presence of environmental allergens than they do a-lone. This immunologic evidence may help explain the epidemiologic studies indicating that children living along major trucking thoroughfares are at increased risk for asthmatic and allergic symptoms and a-re more likely to have objective evidence of respiratory dysfunction.	117	133	2002	10		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Systematic reviews of sublingual immunotherapy (SLIT). P>Allergic rhinitis is common worldwide, with significant morbidity and impact on quality of life. In patients who don't respond adequately to anti-allergic drugs. Subcutaneous allergen immunotherapy is effective although requires specialist administration. Sublingual immunotherapy may represent an effective and safer alternative. This Cochrane systematic review is an update of one published in 2003. We searched Cochrane ENT Group Trials Register, Central, PubMed, EMBASE, CINAHL, Web of Science, Biosis Previews, Cambridge Scientific Abstarcts, mRCT and additional sources. We included randomised, double-blind, placebo- controlled trials of sublingual immunotherapy in adults and children. Two authors selected studies and assessed them for quality. Data were put into RevMan 5.0 for a statistical analysis. We used standardised mean difference (SMD), with a random effect model to combine data. Sixty studies were included, with 49 suitable for meta-analysis. We found significant reductions in symptoms (SMD -0.49; 95%CI (-0.64 to -0.34, P < 0.00001)) and medication requirements (SMD -0.32; 95%CI (-0.43 to -0.21, P < 0.00001)) compared with placebo. None of the trials reported severe systemic reactions, anaphylaxis or use of Adrenaline. This updated review reinforces the conclusion of the original 2003 Cochrane Review that sublingual immunotherapy is effective for allergic rhinitis and appears a safe route of administration.. allergic rhinitis| immunotherapy| systematic review|placebo-controlled trial| grass allergen tablets| randomized controlled-trial| house-dust-mite| standardized 5-grass-pollen extract| parietaria-judaica extract| double-blind| swallow immunotherapy| pollen extract| clinical-efficacy.	JUN-2011	allergic rhinitis| immunotherapy| systematic review|placebo-controlled trial| grass allergen tablets| randomized controlled-trial| house-dust-mite| standardized 5-grass-pollen extract| parietaria-judaica extract| double-blind| swallow immunotherapy| pollen extract| clinical-efficacy	Radulovic, S; Wilson, D; Calderon, M; Durham, S	Systematic reviews of sublingual immunotherapy (SLIT)		ALLERGY	allergic rhinitis; immunotherapy; systematic review	PLACEBO-CONTROLLED TRIAL; GRASS ALLERGEN TABLETS; RANDOMIZED CONTROLLED-TRIAL; HOUSE-DUST-MITE; STANDARDIZED 5-GRASS-POLLEN EXTRACT; PARIETARIA-JUDAICA EXTRACT; DOUBLE-BLIND; SWALLOW IMMUNOTHERAPY; POLLEN EXTRACT; CLINICAL-EFFICACY	P>Allergic rhinitis is common worldwide, with significant morbidity and impact on quality of life. In patients who don't respond adequately to anti-allergic drugs. Subcutaneous allergen immunotherapy is effective although requires specialist administration. Sublingual immunotherapy may represent an effective and safer alternative. This Cochrane systematic review is an update of one published in 2003. We searched Cochrane ENT Group Trials Register, Central, PubMed, EMBASE, CINAHL, Web of Science, Biosis Previews, Cambridge Scientific Abstarcts, mRCT and additional sources. We included randomised, double-blind, placebo- controlled trials of sublingual immunotherapy in adults and children. Two authors selected studies and assessed them for quality. Data were put into RevMan 5.0 for a statistical analysis. We used standardised mean difference (SMD), with a random effect model to combine data. Sixty studies were included, with 49 suitable for meta-analysis. We found significant reductions in symptoms (SMD -0.49; 95%CI (-0.64 to -0.34, P < 0.00001)) and medication requirements (SMD -0.32; 95%CI (-0.43 to -0.21, P < 0.00001)) compared with placebo. None of the trials reported severe systemic reactions, anaphylaxis or use of Adrenaline. This updated review reinforces the conclusion of the original 2003 Cochrane Review that sublingual immunotherapy is effective for allergic rhinitis and appears a safe route of administration.	89	132	2011	13	10.1111/j.1398-9995.2011.02583.x	Allergy; Immunology
Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice. The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC-driven Th2 cell response to harmless inhaled antigens, thereby promoting allergic asthma. However, only a small fraction of people exposed to environmental LIPS develop allergic asthma. What prevents most people from mounting a lung DC-driven Th2 response upon exposure to LPS is not understood. Here we have shown that lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th2 response in mice challenged with LPS and an experimental harmless airborne antigen. IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10-dependent manner. We further demonstrated that specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs, it does not provoke airway allergy under normal conditions.. respiratory syncytial virus| colony-stimulating factor| house-dust endotoxin| alveolar macrophages| in-vivo| inhaled antigen| immune-responses| peritoneal-macrophages| cytokine production| il-12 production.	DEC-2009	respiratory syncytial virus| colony-stimulating factor| house-dust endotoxin| alveolar macrophages| in-vivo| inhaled antigen| immune-responses| peritoneal-macrophages| cytokine production| il-12 production	Bedoret, D; Wallemacq, H; Marichal, T; Desmet, C; Calvo, FQ; Henry, E; Closset, R; Dewals, B; Thielen, C; Gustin, P; de Leval, L; Van Rooijen, N; Le Moine, A; Vanderplasschen, A; Cataldo, D; Drion, PV; Moser, M; Lekeux, P; Bureau, F	Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice		JOURNAL OF CLINICAL INVESTIGATION		RESPIRATORY SYNCYTIAL VIRUS; COLONY-STIMULATING FACTOR; HOUSE-DUST ENDOTOXIN; ALVEOLAR MACROPHAGES; IN-VIVO; INHALED ANTIGEN; IMMUNE-RESPONSES; PERITONEAL-MACROPHAGES; CYTOKINE PRODUCTION; IL-12 PRODUCTION	The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC-driven Th2 cell response to harmless inhaled antigens, thereby promoting allergic asthma. However, only a small fraction of people exposed to environmental LIPS develop allergic asthma. What prevents most people from mounting a lung DC-driven Th2 response upon exposure to LPS is not understood. Here we have shown that lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th2 response in mice challenged with LPS and an experimental harmless airborne antigen. IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10-dependent manner. We further demonstrated that specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs, it does not provoke airway allergy under normal conditions.	67	132	2009	16	10.1172/JCI39717	Research & Experimental Medicine
Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study. Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.. contrast media| hypersensitivity| skin tests|drug hypersensitivity| anaphylaxis| immediate| allergy| guidelines| protocol| risk.	FEB-2009	contrast media| hypersensitivity| skin tests|drug hypersensitivity| anaphylaxis| immediate| allergy| guidelines| protocol| risk	Brockow, K; Romano, A; Aberer, W; Bircher, AJ; Barbaud, A; Bonadonna, P; Faria, E; Kanny, G; Lerch, M; Pichler, WJ; Ring, J; Cernadas, JR; Tomaz, E; Demoly, P; Christiansen, C	Skin testing in patients with hypersensitivity reactions to iodinated contrast media - a European multicenter study		ALLERGY	contrast media; hypersensitivity; skin tests	DRUG HYPERSENSITIVITY; ANAPHYLAXIS; IMMEDIATE; ALLERGY; GUIDELINES; PROTOCOL; RISK	Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions. Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls. Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure. These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.	34	132	2009	8	10.1111/j.1398-9995.2008.01832.x	Allergy; Immunology
A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity. Airway hypersensitive reaction (AHR) is an animal model for asthma, which is caused or enhanced by environmental factors such as allergen exposure. However, the precise mechanisms that drive AHR remain unclear. We identified a novel subset of natural killer T (NKT) cells that expresses the interleukin 17 receptor B (IL-17RB) for IL-25 (also known as IL-17E) and is essential for the induction of AHR. IL-17RB is preferentially expressed on a fraction of CD4(+) NKT cells but not on other splenic leukocyte populations tested. IL-17RB(+) CD4(+) NKT cells produce predominantly IL-13 and Th2 chemokines upon stimulation with IL-25 in vitro. IL-17RB(+) NKT cells were detected in the lung, and depletion of IL-17RB(+) NKT cells by IL-17RB(-)specific monoclonal antibodies or NKT cell deficient J alpha 18(-/-) mice failed to develop IL-25-dependent AHR. Cell transfer of IL-17RB(+) but not IL-17RB(-) NKT cells into J alpha 18(-/-) mice also successfully reconstituted AHR induction. These results strongly suggest that IL-17RB(+) CD4(+) NKT cells play a crucial role in the pathogenesis of asthma.. killer t-cells| in-vivo| allergic-asthma| th2 responses| activation| identification| population| expression| lung| hyperresponsiveness.	NOV 24-2008	killer t-cells| in-vivo| allergic-asthma| th2 responses| activation| identification| population| expression| lung| hyperresponsiveness	Terashima, A; Watarai, H; Inoue, S; Sekine, E; Nakagawa, R; Hase, K; Iwamura, C; Nakajima, H; Nakayama, T; Taniguchi, M	A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity		JOURNAL OF EXPERIMENTAL MEDICINE		KILLER T-CELLS; IN-VIVO; ALLERGIC-ASTHMA; TH2 RESPONSES; ACTIVATION; IDENTIFICATION; POPULATION; EXPRESSION; LUNG; HYPERRESPONSIVENESS	Airway hypersensitive reaction (AHR) is an animal model for asthma, which is caused or enhanced by environmental factors such as allergen exposure. However, the precise mechanisms that drive AHR remain unclear. We identified a novel subset of natural killer T (NKT) cells that expresses the interleukin 17 receptor B (IL-17RB) for IL-25 (also known as IL-17E) and is essential for the induction of AHR. IL-17RB is preferentially expressed on a fraction of CD4(+) NKT cells but not on other splenic leukocyte populations tested. IL-17RB(+) CD4(+) NKT cells produce predominantly IL-13 and Th2 chemokines upon stimulation with IL-25 in vitro. IL-17RB(+) NKT cells were detected in the lung, and depletion of IL-17RB(+) NKT cells by IL-17RB(-)specific monoclonal antibodies or NKT cell deficient J alpha 18(-/-) mice failed to develop IL-25-dependent AHR. Cell transfer of IL-17RB(+) but not IL-17RB(-) NKT cells into J alpha 18(-/-) mice also successfully reconstituted AHR induction. These results strongly suggest that IL-17RB(+) CD4(+) NKT cells play a crucial role in the pathogenesis of asthma.	31	132	2008	10	10.1084/jem.20080698	Immunology; Research & Experimental Medicine
"On the history of indoor air quality and health. Indoor air is a dominant exposure for humans. More that half of the body's intake during a lifetime is air inhaled in the home. Thus, most illnesses related to environmental exposures stem from indoor air exposure. Indoor air was believed to be a major environmental factor for more than a hundred years, from the start of the hygienic revolution, around 1850, until outdoor environmental issues entered the scene, and became dominant around 1960. Main environmental issues today are outdoor air quality, energy use, and sustainable buildings, but not indoor air quality (IAQ). But, there is mounting evidence that exposure to IAQ is the cause of excessive morbidity and mortality. In developing regions indoor unvented burning of biomass for cooking is the cause of at least 2,000,000 deaths a year (mainly women and children), and in the developed world IAQ is a main cause of allergies, other hypersensitivity reactions, airway infections, and cancers. Cancer of the lungs is related to indoor radon and ETS exposure. Allergies, airway infections and sick building syndrome are associated with, e.g., ""dampness"", a low ventilation rate, and plasticizers. In the future more emphasis must be given to IAQ and health issues.. iaq| health| allergy| indoor environments| dampness| ventilation|syndrome sbs symptoms| scientific evidence| environments| ventilation| buildings| exposure| productivity| associations| dampness| office."	AUG-2004	iaq| health| allergy| indoor environments| dampness| ventilation|syndrome sbs symptoms| scientific evidence| environments| ventilation| buildings| exposure| productivity| associations| dampness| office	Sundell, J	On the history of indoor air quality and health		INDOOR AIR	IAQ; health; allergy; indoor environments; dampness; ventilation	SYNDROME SBS SYMPTOMS; SCIENTIFIC EVIDENCE; ENVIRONMENTS; VENTILATION; BUILDINGS; EXPOSURE; PRODUCTIVITY; ASSOCIATIONS; DAMPNESS; OFFICE	"Indoor air is a dominant exposure for humans. More that half of the body's intake during a lifetime is air inhaled in the home. Thus, most illnesses related to environmental exposures stem from indoor air exposure. Indoor air was believed to be a major environmental factor for more than a hundred years, from the start of the hygienic revolution, around 1850, until outdoor environmental issues entered the scene, and became dominant around 1960. Main environmental issues today are outdoor air quality, energy use, and sustainable buildings, but not indoor air quality (IAQ). But, there is mounting evidence that exposure to IAQ is the cause of excessive morbidity and mortality. In developing regions indoor unvented burning of biomass for cooking is the cause of at least 2,000,000 deaths a year (mainly women and children), and in the developed world IAQ is a main cause of allergies, other hypersensitivity reactions, airway infections, and cancers. Cancer of the lungs is related to indoor radon and ETS exposure. Allergies, airway infections and sick building syndrome are associated with, e.g., ""dampness"", a low ventilation rate, and plasticizers. In the future more emphasis must be given to IAQ and health issues."	22	132	2004	8	10.1111/j.1600-0668.2004.00273.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Airway wall remodeling: friend or foe?. Airway wall remodeling is well documented for asthmatic airways and is believed to result from chronic and/or short-term exposure to inflammatory stimuli. Airway wall remodeling can contribute to airway narrowing as well as to the airway hyperresponsiveness, which is a characteristic abnormality in asthma. However, the potential for airway narrowing could be much worse if it were not for some of the protective effects of remodeling that may help to limit airway narrowing in asthmatic patients. This minireview discusses the evidence for airway wall remodeling and its effects, friend and/or foe, on airway narrowing in asthmatic patients.. asthma| pathophysiology| smooth muscle|smooth-muscle cells| obstructive pulmonary-disease| bronchial basement-membrane| dose-response curve| fatal asthma| subepithelial fibrosis| deep inspiration| mild asthma| induced bronchoconstriction| length oscillation.	JUL-2003	asthma| pathophysiology| smooth muscle|smooth-muscle cells| obstructive pulmonary-disease| bronchial basement-membrane| dose-response curve| fatal asthma| subepithelial fibrosis| deep inspiration| mild asthma| induced bronchoconstriction| length oscillation	McParland, BE; Macklem, PT; Pare, PD	Airway wall remodeling: friend or foe?		JOURNAL OF APPLIED PHYSIOLOGY	asthma; pathophysiology; smooth muscle	SMOOTH-MUSCLE CELLS; OBSTRUCTIVE PULMONARY-DISEASE; BRONCHIAL BASEMENT-MEMBRANE; DOSE-RESPONSE CURVE; FATAL ASTHMA; SUBEPITHELIAL FIBROSIS; DEEP INSPIRATION; MILD ASTHMA; INDUCED BRONCHOCONSTRICTION; LENGTH OSCILLATION	Airway wall remodeling is well documented for asthmatic airways and is believed to result from chronic and/or short-term exposure to inflammatory stimuli. Airway wall remodeling can contribute to airway narrowing as well as to the airway hyperresponsiveness, which is a characteristic abnormality in asthma. However, the potential for airway narrowing could be much worse if it were not for some of the protective effects of remodeling that may help to limit airway narrowing in asthmatic patients. This minireview discusses the evidence for airway wall remodeling and its effects, friend and/or foe, on airway narrowing in asthmatic patients.	120	132	2003	9	10.1152/japplphysiol.00159.2003	Physiology; Sport Sciences
Pathology related to chronic arsenic exposure. Millions now suffer the effects of chronic arseniasis related to environmental arsenic exposure. The biological mechanisms responsible for arsenic-induced toxicity and especially chronic effects, including cancer, are not well known. The U.S. Armed Forces Institute of Pathology (AFIP) is participating in an international research effort to improve this understanding by the development of the International Tissue and Tumor Repository for Chronic Arsenosis (ITTRCA). The ITTRCA obtains, archives, and makes available for research purposes, tissues from subjects exposed to arsenic. We provide here a short overview of arsenic-induced pathology, briefly describe arsenic-induced lesions in the skin and liver, and present five case reports from the ITTRCA. Arsenic-induced skin pathology includes hyperkeratosis, pigmentation changes, Bowen disease, squamous cell carcinoma, and basal cell carcinomas. A unique spectrum of skin lesions, known as arsenical keratosis, is rather characteristic of chronic arseniasis. Bowen disease, or squamous cell carcinoma in situ of the skin, has been well documented as a consequence of arsenical exposure. A spectrum of liver lesions has also been attributed to chronic arseniasis. Of these, hepatocellular carcinoma, angiosarcoma, cirrhosis, and hepatoportal sclerosis have been associated with arsenic exposure. We present case reports that relate to these health conditions, namely, squamous cell carcinoma, basal cell carcinoma, and Bowen disease of the skin and hepatocellular carcinoma and angiosarcoma of the liver. Four patients had been treated with arsenical medications for such conditions as asthma, psoriasis, and syphilis, and one case occurred in a boy chronically exposed to arsenic in drinking water.. angiosarcoma| arsenic| bowen disease| hepatocellular carcinoma| hepatoportal sclerosis| hyperkeratosis| liver| noncirrhotic portal fibrosis| squamous cell carcinoma|idiopathic portal-hypertension| drinking-water| well water| mortality| angiosarcoma| prevalence| argentina| diseases.	OCT-2002	angiosarcoma| arsenic| bowen disease| hepatocellular carcinoma| hepatoportal sclerosis| hyperkeratosis| liver| noncirrhotic portal fibrosis| squamous cell carcinoma|idiopathic portal-hypertension| drinking-water| well water| mortality| angiosarcoma| prevalence| argentina| diseases	Centeno, JA; Mullick, FG; Martinez, L; Page, NP; Gibb, H; Longfellow, D; Thompson, C; Ladich, ER	Pathology related to chronic arsenic exposure		ENVIRONMENTAL HEALTH PERSPECTIVES	angiosarcoma; arsenic; Bowen disease; hepatocellular carcinoma; hepatoportal sclerosis; hyperkeratosis; liver; noncirrhotic portal fibrosis; squamous cell carcinoma	IDIOPATHIC PORTAL-HYPERTENSION; DRINKING-WATER; WELL WATER; MORTALITY; ANGIOSARCOMA; PREVALENCE; ARGENTINA; DISEASES	Millions now suffer the effects of chronic arseniasis related to environmental arsenic exposure. The biological mechanisms responsible for arsenic-induced toxicity and especially chronic effects, including cancer, are not well known. The U.S. Armed Forces Institute of Pathology (AFIP) is participating in an international research effort to improve this understanding by the development of the International Tissue and Tumor Repository for Chronic Arsenosis (ITTRCA). The ITTRCA obtains, archives, and makes available for research purposes, tissues from subjects exposed to arsenic. We provide here a short overview of arsenic-induced pathology, briefly describe arsenic-induced lesions in the skin and liver, and present five case reports from the ITTRCA. Arsenic-induced skin pathology includes hyperkeratosis, pigmentation changes, Bowen disease, squamous cell carcinoma, and basal cell carcinomas. A unique spectrum of skin lesions, known as arsenical keratosis, is rather characteristic of chronic arseniasis. Bowen disease, or squamous cell carcinoma in situ of the skin, has been well documented as a consequence of arsenical exposure. A spectrum of liver lesions has also been attributed to chronic arseniasis. Of these, hepatocellular carcinoma, angiosarcoma, cirrhosis, and hepatoportal sclerosis have been associated with arsenic exposure. We present case reports that relate to these health conditions, namely, squamous cell carcinoma, basal cell carcinoma, and Bowen disease of the skin and hepatocellular carcinoma and angiosarcoma of the liver. Four patients had been treated with arsenical medications for such conditions as asthma, psoriasis, and syphilis, and one case occurred in a boy chronically exposed to arsenic in drinking water.	26	132	2002	4		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction. The International Olympic Committee Medical Commission (IOC-MC) requires notification for use of a beta (2) agonist at the Winter Olympic Games in Salt Lake City. This notification will be required seven days before the event and must be accompanied by objective evidence that justifies the need to use one. The IOC-MC has expressed the viewpoint that, at present, eucapnic voluntary hyperpnoea (EVH) is the optimal laboratory challenge to confirm that an athlete has exercise induced bronchoconstriction (EIB). The EVH test recommended was specifically designed to identify EIB. EVH has been performed in thousands of subjects in both the laboratory and the field. The test requires the subject to hyperventilate dry air containing 5% carbon dioxide at room temperature for six minutes at a target ventilation of 30 times the subject's forced expiratory volume in one second (FEV1). The test conditions can be modified to simulate the conditions that give the athlete their symptoms with exercise. A reduction in FEV1 of 10% or more of the value before the test is considered positive.. hyperpnoea| bronchial provocation| exercise|thermally-induced asthma| cold-air| bronchoprovocation technique| induced bronchospasm| dry air| hyperventilation| challenge| responsiveness| reactivity| children.	OCT-2001	hyperpnoea| bronchial provocation| exercise|thermally-induced asthma| cold-air| bronchoprovocation technique| induced bronchospasm| dry air| hyperventilation| challenge| responsiveness| reactivity| children	Anderson, SD; Argyros, GJ; Magnussen, H; Holzer, K	Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction		BRITISH JOURNAL OF SPORTS MEDICINE	hyperpnoea; bronchial provocation; exercise	THERMALLY-INDUCED ASTHMA; COLD-AIR; BRONCHOPROVOCATION TECHNIQUE; INDUCED BRONCHOSPASM; DRY AIR; HYPERVENTILATION; CHALLENGE; RESPONSIVENESS; REACTIVITY; CHILDREN	The International Olympic Committee Medical Commission (IOC-MC) requires notification for use of a beta (2) agonist at the Winter Olympic Games in Salt Lake City. This notification will be required seven days before the event and must be accompanied by objective evidence that justifies the need to use one. The IOC-MC has expressed the viewpoint that, at present, eucapnic voluntary hyperpnoea (EVH) is the optimal laboratory challenge to confirm that an athlete has exercise induced bronchoconstriction (EIB). The EVH test recommended was specifically designed to identify EIB. EVH has been performed in thousands of subjects in both the laboratory and the field. The test requires the subject to hyperventilate dry air containing 5% carbon dioxide at room temperature for six minutes at a target ventilation of 30 times the subject's forced expiratory volume in one second (FEV1). The test conditions can be modified to simulate the conditions that give the athlete their symptoms with exercise. A reduction in FEV1 of 10% or more of the value before the test is considered positive.	30	132	2001	4	10.1136/bjsm.35.5.344	Sport Sciences
Work is related to a substantial portion of adult-onset asthma incidence in the Finnish population. There are no population-based follow-up studies to estimate the fraction of asthma incidence that is attributable to work. In Finland, individuals with clinically well-established persistent asthma are registered for reimbursement of medication from the national health insurance scheme. We combined, at an individual level, these data with the population census data of 1985, 1990, and 1995 to estimate the attributable fraction of work in adult-onset persistent asthma. Our follow-up study covered the entire 25- to 59-yr-old employed population of Finland in 1986-1998. Relative risks (RR) for occupational categories were estimated in comparison to those employed in administrative work. There were 49,575 incident cases of asthma. The attributable fraction of occupation was 29% (95% CI 25-33%) for men and 17% (95% CI 15-19%) for women. The risk was increased especially in agricultural work, manufacturing work, and service work. In addition to already established risk occupations of occupational asthma, such as food and beverage work, the analysis identified a large number of occupations with significant excess of asthma incidence. The results indicate that the impact of occupational factors in the inception of adult-onset persistent asthma, and consequently the potential for prevention, is much larger and more widely spread than generally assumed.. asthma| occupational medicine| risk| incidence| population|occupational asthma| bronchial-asthma| smoking| exposures| risk| finland.	AUG 15-2001	asthma| occupational medicine| risk| incidence| population|occupational asthma| bronchial-asthma| smoking| exposures| risk| finland	Karjalainen, A; Kurppa, K; Martikainen, R; Klaukka, T; Karjalainen, J	Work is related to a substantial portion of adult-onset asthma incidence in the Finnish population		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; occupational medicine; risk; incidence; population	OCCUPATIONAL ASTHMA; BRONCHIAL-ASTHMA; SMOKING; EXPOSURES; RISK; FINLAND	There are no population-based follow-up studies to estimate the fraction of asthma incidence that is attributable to work. In Finland, individuals with clinically well-established persistent asthma are registered for reimbursement of medication from the national health insurance scheme. We combined, at an individual level, these data with the population census data of 1985, 1990, and 1995 to estimate the attributable fraction of work in adult-onset persistent asthma. Our follow-up study covered the entire 25- to 59-yr-old employed population of Finland in 1986-1998. Relative risks (RR) for occupational categories were estimated in comparison to those employed in administrative work. There were 49,575 incident cases of asthma. The attributable fraction of occupation was 29% (95% CI 25-33%) for men and 17% (95% CI 15-19%) for women. The risk was increased especially in agricultural work, manufacturing work, and service work. In addition to already established risk occupations of occupational asthma, such as food and beverage work, the analysis identified a large number of occupations with significant excess of asthma incidence. The results indicate that the impact of occupational factors in the inception of adult-onset persistent asthma, and consequently the potential for prevention, is much larger and more widely spread than generally assumed.	25	132	2001	4		General & Internal Medicine; Respiratory System
Air pollution and exacerbation of asthma in African-American children in Los Angeles. Significant increases in asthma morbidity and mortality in the United States have occurred since the 1970s, particularly among African-Americans. Exposure to various environmental factors, including air pollutants and allergens, has been suggested as a partial explanation of these trends. To examine relations between several air pollutants and asthma exacerbation in African Americans, we recruited a panel of 138 children in central Los Angeles. We recorded daily data on respiratory symptoms and medication use for 13 weeks and examined these data in conjunction with data on ozone (O-3) nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), meteorological variables, pollens, and molds. Using generalized estimating equations, we found associations between respiratory symptom occurrence and several environmental factors. For example, new episodes of cough were associated with exposure to PM10 (OR = 1.25; 95% CI = 1.12-1.39; interquartile range [IQR] = 17 mug/m(3), 24-hour average), PM2.5 (OR = 1.10; 95% CI = 1.03-1.18; IQR = 30 mug/m(3), 12-hour average), NO2, and the molds Cladosporium and Alternaria, but not with exposure to O-3 or pollen. The factors PM10 and O-3 were associated with the use of extra asthma medication. For this population several bioaerosols and air pollutants had effects that may be clinically significant.. air pollution| asthma| children| race| particulate matter| fungi| pollens| environmental exposure|emergency room visits| respiratory health| childhood asthma| ozone exposure| pm10 pollution| acid aerosols| symptoms| severity| admissions| california.	MAR-2001	air pollution| asthma| children| race| particulate matter| fungi| pollens| environmental exposure|emergency room visits| respiratory health| childhood asthma| ozone exposure| pm10 pollution| acid aerosols| symptoms| severity| admissions| california	Ostro, B; Lipsett, M; Mann, J; Braxton-Owens, H; White, M	Air pollution and exacerbation of asthma in African-American children in Los Angeles		EPIDEMIOLOGY	air pollution; asthma; children; race; particulate matter; fungi; pollens; environmental exposure	EMERGENCY ROOM VISITS; RESPIRATORY HEALTH; CHILDHOOD ASTHMA; OZONE EXPOSURE; PM10 POLLUTION; ACID AEROSOLS; SYMPTOMS; SEVERITY; ADMISSIONS; CALIFORNIA	Significant increases in asthma morbidity and mortality in the United States have occurred since the 1970s, particularly among African-Americans. Exposure to various environmental factors, including air pollutants and allergens, has been suggested as a partial explanation of these trends. To examine relations between several air pollutants and asthma exacerbation in African Americans, we recruited a panel of 138 children in central Los Angeles. We recorded daily data on respiratory symptoms and medication use for 13 weeks and examined these data in conjunction with data on ozone (O-3) nitrogen dioxide (NO2), particulate matter (PM10 and PM2.5), meteorological variables, pollens, and molds. Using generalized estimating equations, we found associations between respiratory symptom occurrence and several environmental factors. For example, new episodes of cough were associated with exposure to PM10 (OR = 1.25; 95% CI = 1.12-1.39; interquartile range [IQR] = 17 mug/m(3), 24-hour average), PM2.5 (OR = 1.10; 95% CI = 1.03-1.18; IQR = 30 mug/m(3), 12-hour average), NO2, and the molds Cladosporium and Alternaria, but not with exposure to O-3 or pollen. The factors PM10 and O-3 were associated with the use of extra asthma medication. For this population several bioaerosols and air pollutants had effects that may be clinically significant.	28	132	2001	9	10.1097/00001648-200103000-00012	Public, Environmental & Occupational Health
Manchester Asthma and Allergy Study: Low-allergen environment can be achieved and maintained during pregnancy and in early life. Background: Early exposure to dust mite allergens may be critical for primary sensitization. Reducing exposure may offer a realistic chance for primary prevention of sensitization and asthma, but it is essential to implement measures that can achieve and maintain the low-allergen environment. Objective: Our purpose was to assess the effectiveness of mite allergen avoidance measures in achieving and maintaining a low-allergen environment during pregnancy and in the first year of life. Methods: The Manchester Asthma and Allergy Study is a prospective, prenatally randomized study that follows the development of asthma and atopy in a cohort of infants at high risk (both parents atopic) who are randomly allocated to full mite allergen avoidance or to a normal regimen. Avoidance measures comprise (1) mite-proof covers (mattress, pillow, and quilt) for parental bed, (2) high-filtration vacuum cleaner, (3) vinyl flooring in infant's bedroom, (4) new crib and portable crib mattresses encased in mite-proof material, (5) benzyl benzoate (Acarosan) applied on carpets and soft furniture, (6) bed linens washed in hot water weekly, and (7) washable soft toys. Dust samples from the parental bed, bedroom floor, living room floor, infant's mattress, and nursery floor were collected between the 10th and 14th weeks of pregnancy, immediately after birth, and then at age 6 months and 1 year, and Der p 1 levels were determined by mAb-based ELISA. Results: Recovered Der p 1 from maternal mattress was reduced by 97.25% (95% confidence interval [CI] 95.25%-98.41%) during the second and third trimesters of pregnancy, with the effect persisting for 6 months (98% reduction, 95% CI 97.258-99.1%) and 12 months (97.6% reduction, 95% CI 95.7%-98.6%) after the birth (active vs control, P <.000001). Total Der p 1 from bedroom floor in the active group was reduced by 53.7% (95 % CI 25.7%-71.2%) in samples collected within 4 weeks of the child's birth, with the percentage reduction being 62.8% (95 % CI 39.3%-77.2%) at 6 months and 26.5% (95% CI-24% to 57.1%) at 1 year (active compared vs control, P <.007). Der p 1 levels in crib mattress and nursery floor in the active group were extremely low (crib mattresses geometric mean [95% CI] 2.3 ng [1.6-3.4] at birth, 6.8 ng [4.5-10] at age 6 months, and 15.6 ng [9.8-24.8] at age 1 year [active vs control, P =.001]; nursery 1 ng [0.9-1.1] at birth, 1.7 ng [1.2-2.5] at age 6 months, and 2 ng [1.3-3.5] at age 1 year [active vs control, P <.00001]). The total amount of allergen recovered at age 1 year was 29-fold (95% CI 15.1- to 56.7-fold) higher in the control group than in the active group. Conclusions: The avoidance measures used in this study achieved and maintained a low mite allergen environment during pregnancy and in the first year of life in homes of infants at risk of atopy.. primary prevention| dust mite| avoidance| atopy| asthma|house-dust mite| risk factor| p-i| sensitization| avoidance| childhood| exposure| infancy| population| disorders.	FEB-2000	primary prevention| dust mite| avoidance| atopy| asthma|house-dust mite| risk factor| p-i| sensitization| avoidance| childhood| exposure| infancy| population| disorders	Custovic, A; Simpson, BM; Simpson, A; Hallam, C; Craven, M; Brutsche, M; Woodcock, A	Manchester Asthma and Allergy Study: Low-allergen environment can be achieved and maintained during pregnancy and in early life		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	primary prevention; dust mite; avoidance; atopy; asthma	HOUSE-DUST MITE; RISK FACTOR; P-I; SENSITIZATION; AVOIDANCE; CHILDHOOD; EXPOSURE; INFANCY; POPULATION; DISORDERS	Background: Early exposure to dust mite allergens may be critical for primary sensitization. Reducing exposure may offer a realistic chance for primary prevention of sensitization and asthma, but it is essential to implement measures that can achieve and maintain the low-allergen environment. Objective: Our purpose was to assess the effectiveness of mite allergen avoidance measures in achieving and maintaining a low-allergen environment during pregnancy and in the first year of life. Methods: The Manchester Asthma and Allergy Study is a prospective, prenatally randomized study that follows the development of asthma and atopy in a cohort of infants at high risk (both parents atopic) who are randomly allocated to full mite allergen avoidance or to a normal regimen. Avoidance measures comprise (1) mite-proof covers (mattress, pillow, and quilt) for parental bed, (2) high-filtration vacuum cleaner, (3) vinyl flooring in infant's bedroom, (4) new crib and portable crib mattresses encased in mite-proof material, (5) benzyl benzoate (Acarosan) applied on carpets and soft furniture, (6) bed linens washed in hot water weekly, and (7) washable soft toys. Dust samples from the parental bed, bedroom floor, living room floor, infant's mattress, and nursery floor were collected between the 10th and 14th weeks of pregnancy, immediately after birth, and then at age 6 months and 1 year, and Der p 1 levels were determined by mAb-based ELISA. Results: Recovered Der p 1 from maternal mattress was reduced by 97.25% (95% confidence interval [CI] 95.25%-98.41%) during the second and third trimesters of pregnancy, with the effect persisting for 6 months (98% reduction, 95% CI 97.258-99.1%) and 12 months (97.6% reduction, 95% CI 95.7%-98.6%) after the birth (active vs control, P <.000001). Total Der p 1 from bedroom floor in the active group was reduced by 53.7% (95 % CI 25.7%-71.2%) in samples collected within 4 weeks of the child's birth, with the percentage reduction being 62.8% (95 % CI 39.3%-77.2%) at 6 months and 26.5% (95% CI-24% to 57.1%) at 1 year (active compared vs control, P <.007). Der p 1 levels in crib mattress and nursery floor in the active group were extremely low (crib mattresses geometric mean [95% CI] 2.3 ng [1.6-3.4] at birth, 6.8 ng [4.5-10] at age 6 months, and 15.6 ng [9.8-24.8] at age 1 year [active vs control, P =.001]; nursery 1 ng [0.9-1.1] at birth, 1.7 ng [1.2-2.5] at age 6 months, and 2 ng [1.3-3.5] at age 1 year [active vs control, P <.00001]). The total amount of allergen recovered at age 1 year was 29-fold (95% CI 15.1- to 56.7-fold) higher in the control group than in the active group. Conclusions: The avoidance measures used in this study achieved and maintained a low mite allergen environment during pregnancy and in the first year of life in homes of infants at risk of atopy.	27	132	2000	7	10.1016/S0091-6749(00)90073-3	Allergy; Immunology
Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI). Patients with severe refractory asthma pose a major healthcare problem. Over the last decade it has become increasingly clear that, for the development of new targeted therapies, there is an urgent need for further characterisation and classification of these patients. The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) consortium is a pan-European public-private collaboration funded by the European Commission Innovative Medicines Initiative of the European Union. U-BIOPRED aims to subphenotype patients with severe refractory asthma by using an innovative systems biology approach. This paper presents the U-BIOPRED international consensus on the definition and diagnosis of severe asthma, aligning the latest concepts in adults as well as in children. The consensus is based on existing recommendations up to 2010 and will be used for the selection of patients for the upcoming U-BIOPRED study. It includes the differentiation between 'problematic', 'difficult' and 'severe refractory' asthma, and provides a systematic algorithmic approach to the evaluation of patients presenting with chronic severe asthma symptoms for use in clinical research and specialised care.. to-treat asthma| randomized controlled-trial| air-flow limitation| lung-function| sputum eosinophilia| research-program| clinical characteristics| inhaled corticosteroids| gastroesophageal-reflux| occupational asthma.	OCT-2011	to-treat asthma| randomized controlled-trial| air-flow limitation| lung-function| sputum eosinophilia| research-program| clinical characteristics| inhaled corticosteroids| gastroesophageal-reflux| occupational asthma	Bel, EH; Sousa, A; Fleming, L; Bush, A; Chung, KF; Versnel, J; Wagener, AH; Wagers, SS; Sterk, PJ; Compton, CH	Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI)		THORAX		TO-TREAT ASTHMA; RANDOMIZED CONTROLLED-TRIAL; AIR-FLOW LIMITATION; LUNG-FUNCTION; SPUTUM EOSINOPHILIA; RESEARCH-PROGRAM; CLINICAL CHARACTERISTICS; INHALED CORTICOSTEROIDS; GASTROESOPHAGEAL-REFLUX; OCCUPATIONAL ASTHMA	Patients with severe refractory asthma pose a major healthcare problem. Over the last decade it has become increasingly clear that, for the development of new targeted therapies, there is an urgent need for further characterisation and classification of these patients. The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) consortium is a pan-European public-private collaboration funded by the European Commission Innovative Medicines Initiative of the European Union. U-BIOPRED aims to subphenotype patients with severe refractory asthma by using an innovative systems biology approach. This paper presents the U-BIOPRED international consensus on the definition and diagnosis of severe asthma, aligning the latest concepts in adults as well as in children. The consensus is based on existing recommendations up to 2010 and will be used for the selection of patients for the upcoming U-BIOPRED study. It includes the differentiation between 'problematic', 'difficult' and 'severe refractory' asthma, and provides a systematic algorithmic approach to the evaluation of patients presenting with chronic severe asthma symptoms for use in clinical research and specialised care.	82	131	2011	8	10.1136/thx.2010.153643	Respiratory System
Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Background and objective: The last systematic review on the health consequences of child and adolescent obesity found little evidence on consequences for adult health. The present study aimed to summarize evidence on the long-term impact of child and adolescent obesity for premature mortality and physical morbidity in adulthood. Methods: Systematic review with evidence searched from January 2002 to June 2010. Studies were included if they contained a measure of overweight and/or obesity between birth and 18 years (exposure measure) and premature mortality and physical morbidity (outcome) in adulthood. Results: Five eligible studies examined associations between overweight and/or obesity, and premature mortality: 4/5 found significantly increased risk of premature mortality with child and adolescent overweight or obesity. All 11 studies with cardiometabolic morbidity as outcomes reported that overweight and obesity were associated with significantly increased risk of later cardiometabolic morbidity (diabetes, hypertension, ischaemic heart disease, and stroke) in adult life, with hazard ratios ranging from 1.1-5.1. Nine studies examined associations of child or adolescent overweight and obesity with other adult morbidity: studies of cancer morbidity were inconsistent; child and adolescent overweight and obesity were associated with significantly increased risk of later disability pension, asthma, and polycystic ovary syndrome symptoms. Conclusions: A relatively large and fairly consistent body of evidence now demonstrates that overweight and obesity in childhood and adolescence have adverse consequences on premature mortality and physical morbidity in adulthood. International Journal of Obesity (2011) 35, 891-898; doi: 10.1038/ijo.2010.222; published online 26 October 2010. overweight| child| bmi| morbidity|body-mass index| coronary-heart-disease| cardiovascular risk-factors| young adulthood| follow-up| blood-pressure| breast-cancer| life-course| middle-age| subsequent mortality.	JUL-2011	overweight| child| bmi| morbidity|body-mass index| coronary-heart-disease| cardiovascular risk-factors| young adulthood| follow-up| blood-pressure| breast-cancer| life-course| middle-age| subsequent mortality	Reilly, JJ; Kelly, J	Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review		INTERNATIONAL JOURNAL OF OBESITY	overweight; child; BMI; morbidity	BODY-MASS INDEX; CORONARY-HEART-DISEASE; CARDIOVASCULAR RISK-FACTORS; YOUNG ADULTHOOD; FOLLOW-UP; BLOOD-PRESSURE; BREAST-CANCER; LIFE-COURSE; MIDDLE-AGE; SUBSEQUENT MORTALITY	Background and objective: The last systematic review on the health consequences of child and adolescent obesity found little evidence on consequences for adult health. The present study aimed to summarize evidence on the long-term impact of child and adolescent obesity for premature mortality and physical morbidity in adulthood. Methods: Systematic review with evidence searched from January 2002 to June 2010. Studies were included if they contained a measure of overweight and/or obesity between birth and 18 years (exposure measure) and premature mortality and physical morbidity (outcome) in adulthood. Results: Five eligible studies examined associations between overweight and/or obesity, and premature mortality: 4/5 found significantly increased risk of premature mortality with child and adolescent overweight or obesity. All 11 studies with cardiometabolic morbidity as outcomes reported that overweight and obesity were associated with significantly increased risk of later cardiometabolic morbidity (diabetes, hypertension, ischaemic heart disease, and stroke) in adult life, with hazard ratios ranging from 1.1-5.1. Nine studies examined associations of child or adolescent overweight and obesity with other adult morbidity: studies of cancer morbidity were inconsistent; child and adolescent overweight and obesity were associated with significantly increased risk of later disability pension, asthma, and polycystic ovary syndrome symptoms. Conclusions: A relatively large and fairly consistent body of evidence now demonstrates that overweight and obesity in childhood and adolescence have adverse consequences on premature mortality and physical morbidity in adulthood. International Journal of Obesity (2011) 35, 891-898; doi: 10.1038/ijo.2010.222; published online 26 October 2010	66	131	2011	8	10.1038/ijo.2010.222	Endocrinology & Metabolism; Nutrition & Dietetics
Effector and regulatory mechanisms in allergic contact dermatitis. Allergic contact dermatitis (ACD), one of the commonest occupational diseases, is a T-cell-mediated skin inflammation caused by repeated skin exposure to contact allergens, i.e. nonprotein chemicals called haptens. Allergic contact dermatitis, also referred to as contact hypersensitivity, is mediated by CD8+ T cells, which are primed in lymphoid organs during the sensitization phase and are recruited in the skin upon re-exposure to the hapten. Subsets of CD4+ T cells endowed with suppressive activity are responsible for both the down-regulation of eczema in allergic patients and the prevention of priming to haptens in nonallergic individuals. Therefore, ACD should be considered as a breakdown of the skin immune tolerance to haptens. Recent advances in the pathophysiology of ACD have demonstrated the important role of skin innate immunity in the sensitization process and have revisited the dogma that Langerhans cells are mandatory for CD8+ T-cell priming. They have also introduced mast cells as a pivotal actor in the magnitude of the inflammatory reaction. Finally, the most recent studies address the nature, the mode and the site of action of the regulatory T cells that control the skin inflammation with the aim of developing new strategies of tolerance induction in allergic patients.. allergic contact dermatitis| cd4+regulatory t cells| cd8+effector t cells| haptens| mast cells|cd8(+) t-cells| delayed-type hypersensitivity| langerin(+) dendritic cells| epidermal langerhans cells| major histocompatibility complex| cutaneous lymphocyte antigen| in-vivo| immune-responses| inflammatory responses| skin sensitization.	DEC-2009	allergic contact dermatitis| cd4+regulatory t cells| cd8+effector t cells| haptens| mast cells|cd8(+) t-cells| delayed-type hypersensitivity| langerin(+) dendritic cells| epidermal langerhans cells| major histocompatibility complex| cutaneous lymphocyte antigen| in-vivo| immune-responses| inflammatory responses| skin sensitization	Vocanson, M; Hennino, A; Rozieres, A; Poyet, G; Nicolas, JF	Effector and regulatory mechanisms in allergic contact dermatitis		ALLERGY	allergic contact dermatitis; CD4+regulatory T cells; CD8+effector T cells; haptens; mast cells	CD8(+) T-CELLS; DELAYED-TYPE HYPERSENSITIVITY; LANGERIN(+) DENDRITIC CELLS; EPIDERMAL LANGERHANS CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; CUTANEOUS LYMPHOCYTE ANTIGEN; IN-VIVO; IMMUNE-RESPONSES; INFLAMMATORY RESPONSES; SKIN SENSITIZATION	Allergic contact dermatitis (ACD), one of the commonest occupational diseases, is a T-cell-mediated skin inflammation caused by repeated skin exposure to contact allergens, i.e. nonprotein chemicals called haptens. Allergic contact dermatitis, also referred to as contact hypersensitivity, is mediated by CD8+ T cells, which are primed in lymphoid organs during the sensitization phase and are recruited in the skin upon re-exposure to the hapten. Subsets of CD4+ T cells endowed with suppressive activity are responsible for both the down-regulation of eczema in allergic patients and the prevention of priming to haptens in nonallergic individuals. Therefore, ACD should be considered as a breakdown of the skin immune tolerance to haptens. Recent advances in the pathophysiology of ACD have demonstrated the important role of skin innate immunity in the sensitization process and have revisited the dogma that Langerhans cells are mandatory for CD8+ T-cell priming. They have also introduced mast cells as a pivotal actor in the magnitude of the inflammatory reaction. Finally, the most recent studies address the nature, the mode and the site of action of the regulatory T cells that control the skin inflammation with the aim of developing new strategies of tolerance induction in allergic patients.	159	131	2009	16	10.1111/j.1398-9995.2009.02082.x	Allergy; Immunology
Oral tolerance, food allergy, and immunotherapy: Implications for future treatment. The lumen of the gastrointestinal tract is exposed daily to an array of dietary proteins. The vast majority of proteins are tolerated through suppression of cellular or Immoral responses, a process known as oral tolerance. However, in approximately 6% of children and 4% of adults in the United States, tolerance to a given dietary antigen either is not established or breaks down, resulting in food hypersensitivity. Although food allergies can result in sudden and life-threatening symptoms, their prevalence is remarkably low considering the complexities of the gut-associated mucosal system. Suppression involves signaling by an array of nonprofessional antigen-presenting cells, dendritic cells, and regulatory T cells, as well as lymphocyte anergy or deletion. Several factors, including antigen properties, route of exposure, and genetics and age of the host, contribute to the development of oral tolerance. Although the current standard of care for patients with food allergies is based on avoidance of the trigger, increased understanding of the mechanisms involved in tolerance has shifted focus of treatment and prevention toward inducing tolerance. Data from early-phase clinical trials suggest both sublingual and oral immunotherapy are effective in reducing sensitivity to allergens. In this article we review the mechanisms of tolerance, discuss aberrations in oral tolerance, and provide information on novel prevention and treatment paradigms for food allergy.. immune tolerance| immunotherapy| food allergy| food hypersensitivity| t cells| tgf-beta| clonal anergy| forkhead box p3 protein| sublingual immunotherapy| oral immunotherapy|regulatory t-cells| cows milk allergy| growth-factor-beta| quality-of-life| peanut allergy| tgf-beta| active suppression| immune-responses| small-intestine| murine model.	JUN-2008	immune tolerance| immunotherapy| food allergy| food hypersensitivity| t cells| tgf-beta| clonal anergy| forkhead box p3 protein| sublingual immunotherapy| oral immunotherapy|regulatory t-cells| cows milk allergy| growth-factor-beta| quality-of-life| peanut allergy| tgf-beta| active suppression| immune-responses| small-intestine| murine model	Burks, AW; Laubach, S; Jones, SM	Oral tolerance, food allergy, and immunotherapy: Implications for future treatment		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	immune tolerance; immunotherapy; food allergy; food hypersensitivity; T cells; TGF-beta; clonal anergy; forkhead box P3 protein; sublingual immunotherapy; oral immunotherapy	REGULATORY T-CELLS; COWS MILK ALLERGY; GROWTH-FACTOR-BETA; QUALITY-OF-LIFE; PEANUT ALLERGY; TGF-BETA; ACTIVE SUPPRESSION; IMMUNE-RESPONSES; SMALL-INTESTINE; MURINE MODEL	The lumen of the gastrointestinal tract is exposed daily to an array of dietary proteins. The vast majority of proteins are tolerated through suppression of cellular or Immoral responses, a process known as oral tolerance. However, in approximately 6% of children and 4% of adults in the United States, tolerance to a given dietary antigen either is not established or breaks down, resulting in food hypersensitivity. Although food allergies can result in sudden and life-threatening symptoms, their prevalence is remarkably low considering the complexities of the gut-associated mucosal system. Suppression involves signaling by an array of nonprofessional antigen-presenting cells, dendritic cells, and regulatory T cells, as well as lymphocyte anergy or deletion. Several factors, including antigen properties, route of exposure, and genetics and age of the host, contribute to the development of oral tolerance. Although the current standard of care for patients with food allergies is based on avoidance of the trigger, increased understanding of the mechanisms involved in tolerance has shifted focus of treatment and prevention toward inducing tolerance. Data from early-phase clinical trials suggest both sublingual and oral immunotherapy are effective in reducing sensitivity to allergens. In this article we review the mechanisms of tolerance, discuss aberrations in oral tolerance, and provide information on novel prevention and treatment paradigms for food allergy.	61	131	2008	7	10.1016/j.jaci.2008.02.037	Allergy; Immunology
Associations between health effects and particulate matter and black carbon in subjects with respiratory disease. We measured fractional exhaled nitric oxide (FENO), spirometry, blood pressure, oxygen saturation of the blood (SaO(2)), and pulse rate in 16 older subjects with asthma or chronic obstructive pulmonary disease (COPD) in Seattle, Washington. Data were collected daily for 12 days. We simultaneously collected PM10 and PM2.5 (particulate matter <= 10 mu m or <= 2.5 mu m, respectively) filter samples at a central outdoor site, as well as outside and inside the subjects' homes. Personal PM10 filter samples were also collected. All filters were analyzed for mass and light absorbance. We analyzed within-subject associations between health outcomes and air pollution metrics using a linear mixed-effects model with random intercept, controlling for age, ambient relative humidity, and ambient temperature. For the 7 subjects with asthma, a 10 mu g/m(3) increase in 24-hr average outdoor PM10 and PM2.5 was associated with a 5.9 [95% confidence interval (CI), 2.9-8.9] and 4.2 ppb (95% CI, 1.3-7.1) increase in FENO, respectively. A 1 mu g/m(3) increase in outdoor, indoor, and personal black carbon (BC) was associated with increases in FENO of 2.3 ppb (95% Cl, 1.1-3.6), 4.0 ppb (95% CI, 2.0-5.9), and 1.2 ppb (95% Cl, 0.2-2.2), respectively. No significant association was found between PM or BC measures and changes in spirometry, blood pressure, pulse rate, or SaO(2) in these subjects. Results from this study indicate that FENO may be a more sensitive market of PM exposure than traditional health outcomes and that particle-associated BC is useful for examining associations between primary combustion constituents of PM and health outcomes.. asthma| black carbon| chronic obstructive pulmonary disease| fractional exhaled nitric oxide| panel study| particulate matter|exhaled nitric-oxide| obstructive pulmonary-disease| ambient air-pollution| short-term exposure| source apportionment| ultrafine particles| asthmatic-children| oxygen-saturation| fine particles| lung-function.	DEC-2005	asthma| black carbon| chronic obstructive pulmonary disease| fractional exhaled nitric oxide| panel study| particulate matter|exhaled nitric-oxide| obstructive pulmonary-disease| ambient air-pollution| short-term exposure| source apportionment| ultrafine particles| asthmatic-children| oxygen-saturation| fine particles| lung-function	Jansen, KL; Larson, TV; Koenig, JQ; Mar, TF; Fields, C; Stewart, J; Lippmann, M	Associations between health effects and particulate matter and black carbon in subjects with respiratory disease		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; black carbon; chronic obstructive pulmonary disease; fractional exhaled nitric oxide; panel study; particulate matter	EXHALED NITRIC-OXIDE; OBSTRUCTIVE PULMONARY-DISEASE; AMBIENT AIR-POLLUTION; SHORT-TERM EXPOSURE; SOURCE APPORTIONMENT; ULTRAFINE PARTICLES; ASTHMATIC-CHILDREN; OXYGEN-SATURATION; FINE PARTICLES; LUNG-FUNCTION	We measured fractional exhaled nitric oxide (FENO), spirometry, blood pressure, oxygen saturation of the blood (SaO(2)), and pulse rate in 16 older subjects with asthma or chronic obstructive pulmonary disease (COPD) in Seattle, Washington. Data were collected daily for 12 days. We simultaneously collected PM10 and PM2.5 (particulate matter <= 10 mu m or <= 2.5 mu m, respectively) filter samples at a central outdoor site, as well as outside and inside the subjects' homes. Personal PM10 filter samples were also collected. All filters were analyzed for mass and light absorbance. We analyzed within-subject associations between health outcomes and air pollution metrics using a linear mixed-effects model with random intercept, controlling for age, ambient relative humidity, and ambient temperature. For the 7 subjects with asthma, a 10 mu g/m(3) increase in 24-hr average outdoor PM10 and PM2.5 was associated with a 5.9 [95% confidence interval (CI), 2.9-8.9] and 4.2 ppb (95% CI, 1.3-7.1) increase in FENO, respectively. A 1 mu g/m(3) increase in outdoor, indoor, and personal black carbon (BC) was associated with increases in FENO of 2.3 ppb (95% Cl, 1.1-3.6), 4.0 ppb (95% CI, 2.0-5.9), and 1.2 ppb (95% Cl, 0.2-2.2), respectively. No significant association was found between PM or BC measures and changes in spirometry, blood pressure, pulse rate, or SaO(2) in these subjects. Results from this study indicate that FENO may be a more sensitive market of PM exposure than traditional health outcomes and that particle-associated BC is useful for examining associations between primary combustion constituents of PM and health outcomes.	59	131	2005	6	10.1289/ehp.8153	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Glutathione S transferase deficiency and passive smoking increase childhood asthma. Background: It has been suggested that the genetically determined deficiency of glutathione S transferase (GST) enzymes involved in the detoxification of environmental tobacco smoke (ETS) components may contribute to the development of asthma. Methods: A large population of German schoolchildren (n = 3054) was genotyped for deficiencies of the GST isoforms M1 and T1. The association between GSTM1 and GSTT1 genotypes and asthma as well as atopy was investigated with respect to current and in utero ETS exposure. Results: In children lacking the GSTM1 allele who were exposed to current ETS the risk for current asthma (OR 5.5, 95% CI 1.6 to 18.6) and asthma symptoms such as wheeze ever (OR 2.8, 95% CI 1.3 to 6.0), current wheezing (OR 4.7, 95% CI 1.8 to 12.6) and shortness of breath (OR 8.9, 95% CI 2.1 to 38.4) was higher than in GSTM1 positive individuals without ETS exposure. Hints of an interaction between ETS exposure and GSTM1 deficiency were identified. In utero smoke exposure in GSTT1 deficient children was associated with significant decrements in lung function compared with GSTT1 positive children not exposed to ETS. Conclusions: GSTM1 and GSTT1 deficiency may increase the adverse health effects of in utero and current smoke exposure.. environmental tobacco-smoke| parental smoking| spirometric indexes| lung-function| children| polymorphisms| m1| prevalence| genotypes| gene.	JUL-2004	environmental tobacco-smoke| parental smoking| spirometric indexes| lung-function| children| polymorphisms| m1| prevalence| genotypes| gene	Kabesch, M; Hoefler, C; Carr, D; Leupold, W; Weiland, SK; von Mutius, E	Glutathione S transferase deficiency and passive smoking increase childhood asthma		THORAX		ENVIRONMENTAL TOBACCO-SMOKE; PARENTAL SMOKING; SPIROMETRIC INDEXES; LUNG-FUNCTION; CHILDREN; POLYMORPHISMS; M1; PREVALENCE; GENOTYPES; GENE	Background: It has been suggested that the genetically determined deficiency of glutathione S transferase (GST) enzymes involved in the detoxification of environmental tobacco smoke (ETS) components may contribute to the development of asthma. Methods: A large population of German schoolchildren (n = 3054) was genotyped for deficiencies of the GST isoforms M1 and T1. The association between GSTM1 and GSTT1 genotypes and asthma as well as atopy was investigated with respect to current and in utero ETS exposure. Results: In children lacking the GSTM1 allele who were exposed to current ETS the risk for current asthma (OR 5.5, 95% CI 1.6 to 18.6) and asthma symptoms such as wheeze ever (OR 2.8, 95% CI 1.3 to 6.0), current wheezing (OR 4.7, 95% CI 1.8 to 12.6) and shortness of breath (OR 8.9, 95% CI 2.1 to 38.4) was higher than in GSTM1 positive individuals without ETS exposure. Hints of an interaction between ETS exposure and GSTM1 deficiency were identified. In utero smoke exposure in GSTT1 deficient children was associated with significant decrements in lung function compared with GSTT1 positive children not exposed to ETS. Conclusions: GSTM1 and GSTT1 deficiency may increase the adverse health effects of in utero and current smoke exposure.	25	131	2004	5	10.1136/thx.2003.016667	Respiratory System
Breastfeeding and the risk of hospitalization for respiratory disease in infancy - A meta-analysis. Objective: To examine breastfeeding and the risk of hospitalization for lower respiratory tract disease in healthy full-term infants with access to modern medical care. Data Sources: MEDLINE, personal communication with researchers, the OVID databases, Dissertation Abstracts Online, and BIOSIS. Study Selection: The titles, abstracts, and text of studies from developed countries were explored for breastfeeding exposure measures and lower respiratory tract disease hospitalization rates. For summary statistics, we required 3 inclusion criteria: (1) a feeding contrast of a minimum of 2 months of exclusive breastfeeding (no formula supplementation) vs no breastfeeding and (2) study populations that excluded sick, low birth weight or premature infants and (3) reflected affluent regions; 27% of studies met these criteria. Data Extraction: We abstracted data from all relevant reports. Data Synthesis: Data from all primary material (33 studies) indicated a protective association between breastfeeding and the risk of respiratory disease hospitalization. Nine studies met all inclusion criteria, and 7 cohort studies were pooled. The feeding contrasts in these 7 studies were 4 or more months of exclusive breastfeeding vs no breastfeeding. The summary relative risk (95% confidence interval) was 0.28 (0.14-0.54), using a random-effects model. This effect remained stable and statistically significant after adjusting for the effects of smoking or socioeconomic status. Conclusion: Among generally healthy infants in developed nations, more than a tripling in severe respiratory tract illnesses resulting in hospitalizations was noted for infants who were not breastfed compared with those who were exclusively breastfed for 4 months.. syncytial virus-infection| breast-feeding definitions| parental smoking| passive smoking| atopic disease| asthma| children| bronchiolitis| illness| association.	MAR-2003	syncytial virus-infection| breast-feeding definitions| parental smoking| passive smoking| atopic disease| asthma| children| bronchiolitis| illness| association	Bachrach, VRG; Schwarz, E; Bachrach, LR	Breastfeeding and the risk of hospitalization for respiratory disease in infancy - A meta-analysis		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		SYNCYTIAL VIRUS-INFECTION; BREAST-FEEDING DEFINITIONS; PARENTAL SMOKING; PASSIVE SMOKING; ATOPIC DISEASE; ASTHMA; CHILDREN; BRONCHIOLITIS; ILLNESS; ASSOCIATION	Objective: To examine breastfeeding and the risk of hospitalization for lower respiratory tract disease in healthy full-term infants with access to modern medical care. Data Sources: MEDLINE, personal communication with researchers, the OVID databases, Dissertation Abstracts Online, and BIOSIS. Study Selection: The titles, abstracts, and text of studies from developed countries were explored for breastfeeding exposure measures and lower respiratory tract disease hospitalization rates. For summary statistics, we required 3 inclusion criteria: (1) a feeding contrast of a minimum of 2 months of exclusive breastfeeding (no formula supplementation) vs no breastfeeding and (2) study populations that excluded sick, low birth weight or premature infants and (3) reflected affluent regions; 27% of studies met these criteria. Data Extraction: We abstracted data from all relevant reports. Data Synthesis: Data from all primary material (33 studies) indicated a protective association between breastfeeding and the risk of respiratory disease hospitalization. Nine studies met all inclusion criteria, and 7 cohort studies were pooled. The feeding contrasts in these 7 studies were 4 or more months of exclusive breastfeeding vs no breastfeeding. The summary relative risk (95% confidence interval) was 0.28 (0.14-0.54), using a random-effects model. This effect remained stable and statistically significant after adjusting for the effects of smoking or socioeconomic status. Conclusion: Among generally healthy infants in developed nations, more than a tripling in severe respiratory tract illnesses resulting in hospitalizations was noted for infants who were not breastfed compared with those who were exclusively breastfed for 4 months.	72	131	2003	7		Pediatrics
Effect of passive smoking on respiratory symptoms, bronchial responsiveness, lung function, and total serum IgE in the European Community Respiratory Health Survey: a cross-sectional study. Background Passive smoking is widespread, and environmental tobacco smoke contains many potent respiratory irritants. This analysis aimed to estimate the effect of passive smoking on respiratory symptoms, bronchial responsiveness, lung function, and total serum IgE in the European Community Respiratory Health Survey. Methods This analysis included data from 7882 adults (age 20-48 years) who had never smoked, from 36 centres in.16 countries. Information on passive smoking, respiratory symptoms, asthma, and allergic rhinitis was gathered through a structured interview. Spirometry and methacholine challenge were carried out, and total and specific IgE were measured. The effect of passive smoking was estimated by means of logistic and multiple linear regression for each country and combined across countries by random-effects meta-analysis. Findings In 12 of the 36 centres, more than half the participants were regularly involuntarily exposed to tobacco smoke. The prevalence of passive smoking in the workplace varied from 2.5% in Uppsala, Sweden, to 53.8% in Galdalkao, Spain. Passive smoking was significantly associated with nocturnal chest tightness (odds ratio 1.28 [95% CI 1.02 to 1.60]), nocturnal breathlessness (1.30 [1.01 to 1.67]), breathlessness after activity (1.25 [1.07 to 1.47]), and increased bronchial responsiveness (effect -0.18 [-0.30 to -0.05]). Passive smoking in the workplace was significantly associated with all types of respiratory symptoms and current asthma (odds ratio 1.90 [95% CI 0.90 to 2.88]). No significant association was found between passive smoking and total serum IgE. Interpretation Passive smoking is common but the prevalence varies widely between different countries, Passive smoking increased the likelihood of experiencing respiratory symptoms and was associated with increased bronchial responsiveness. Decreasing involuntary exposure to tobacco smoke in the community, especially in workplaces, is likely to improve respiratory health.. environmental tobacco-smoke| pulmonary-function| parental smoking| asthma| exposure| adults| sensitization| population| women| hyperresponsiveness.	DEC 22-2001	environmental tobacco-smoke| pulmonary-function| parental smoking| asthma| exposure| adults| sensitization| population| women| hyperresponsiveness	Janson, C; Chinn, S; Jarvis, D; Zock, JP; Toren, K; Burney, P	Effect of passive smoking on respiratory symptoms, bronchial responsiveness, lung function, and total serum IgE in the European Community Respiratory Health Survey: a cross-sectional study		LANCET		ENVIRONMENTAL TOBACCO-SMOKE; PULMONARY-FUNCTION; PARENTAL SMOKING; ASTHMA; EXPOSURE; ADULTS; SENSITIZATION; POPULATION; WOMEN; HYPERRESPONSIVENESS	Background Passive smoking is widespread, and environmental tobacco smoke contains many potent respiratory irritants. This analysis aimed to estimate the effect of passive smoking on respiratory symptoms, bronchial responsiveness, lung function, and total serum IgE in the European Community Respiratory Health Survey. Methods This analysis included data from 7882 adults (age 20-48 years) who had never smoked, from 36 centres in.16 countries. Information on passive smoking, respiratory symptoms, asthma, and allergic rhinitis was gathered through a structured interview. Spirometry and methacholine challenge were carried out, and total and specific IgE were measured. The effect of passive smoking was estimated by means of logistic and multiple linear regression for each country and combined across countries by random-effects meta-analysis. Findings In 12 of the 36 centres, more than half the participants were regularly involuntarily exposed to tobacco smoke. The prevalence of passive smoking in the workplace varied from 2.5% in Uppsala, Sweden, to 53.8% in Galdalkao, Spain. Passive smoking was significantly associated with nocturnal chest tightness (odds ratio 1.28 [95% CI 1.02 to 1.60]), nocturnal breathlessness (1.30 [1.01 to 1.67]), breathlessness after activity (1.25 [1.07 to 1.47]), and increased bronchial responsiveness (effect -0.18 [-0.30 to -0.05]). Passive smoking in the workplace was significantly associated with all types of respiratory symptoms and current asthma (odds ratio 1.90 [95% CI 0.90 to 2.88]). No significant association was found between passive smoking and total serum IgE. Interpretation Passive smoking is common but the prevalence varies widely between different countries, Passive smoking increased the likelihood of experiencing respiratory symptoms and was associated with increased bronchial responsiveness. Decreasing involuntary exposure to tobacco smoke in the community, especially in workplaces, is likely to improve respiratory health.	34	131	2001	7	10.1016/S0140-6736(01)07214-2	General & Internal Medicine
Ultrafine particles and nitrogen oxides generated by gas and electric cooking. Objectives - To measure the concentrations of particles less than 100 nm diameter and of oxides of nitrogen generated by cooking with gas and electricity, to comment on possible hazards to health in poorly ventilated kitchens. Methods - Experiments with gas and electric rings, grills, and ovens were used to compare different cooking procedures. Nitrogen oxides (NO,) were measured by a chemiluminescent ML9841A NO, analyser. A TSI 3934 scanning mobility particle sizer was used to measure average number concentration and size distribution of aerosols in the size range 10-500 nm. Results-High concentrations of particles are generated by gas combustion, by frying, and by cooking of fatty foods. Electric rings and grills may also generate particles from their surfaces. In experiments where gas burning was the most important source of particles, most particles were in the size range 15-40 nm. When bacon was fried on the gas or electric rings the particles were of larger diameter, in the size range 50-100 nm. The smaller particles generated during experiments grew in size with time because of coagulation. Substantial concentrations of NO, were generated during cooking on gas; four rings for 15 minutes produced 5 minute peaks of about 1000 ppb nitrogen dioxide and about 2000 ppb nitric oxide. Conclusions - Cooking in a poorly ventilated kitchen may give rise to potentially toxic concentrations of numbers of particles. Very high concentrations of oxides of nitrogen may also be generated by gas cooking, and with no extraction and poor ventilation, may reach concentrations at which adverse health effects may be expected. Although respiratory effects of exposure to NO, might be anticipated, recent epidemiology suggests that cardiac effects cannot be excluded, and further investigation of this is desirable.. cooking fuels| nitrogen oxides| ultrafine particles|particulate air-pollution| personal exposure| respiratory symptoms| dioxide exposure| lung-cancer| pulmonary toxicity| inhaled allergen| pm10 pollution| children| health.	AUG-2001	cooking fuels| nitrogen oxides| ultrafine particles|particulate air-pollution| personal exposure| respiratory symptoms| dioxide exposure| lung-cancer| pulmonary toxicity| inhaled allergen| pm10 pollution| children| health	Dennekamp, M; Howarth, S; Dick, CAJ; Cherrie, JW; Donaldson, K; Seaton, A	Ultrafine particles and nitrogen oxides generated by gas and electric cooking		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE	cooking fuels; nitrogen oxides; ultrafine particles	PARTICULATE AIR-POLLUTION; PERSONAL EXPOSURE; RESPIRATORY SYMPTOMS; DIOXIDE EXPOSURE; LUNG-CANCER; PULMONARY TOXICITY; INHALED ALLERGEN; PM10 POLLUTION; CHILDREN; HEALTH	Objectives - To measure the concentrations of particles less than 100 nm diameter and of oxides of nitrogen generated by cooking with gas and electricity, to comment on possible hazards to health in poorly ventilated kitchens. Methods - Experiments with gas and electric rings, grills, and ovens were used to compare different cooking procedures. Nitrogen oxides (NO,) were measured by a chemiluminescent ML9841A NO, analyser. A TSI 3934 scanning mobility particle sizer was used to measure average number concentration and size distribution of aerosols in the size range 10-500 nm. Results-High concentrations of particles are generated by gas combustion, by frying, and by cooking of fatty foods. Electric rings and grills may also generate particles from their surfaces. In experiments where gas burning was the most important source of particles, most particles were in the size range 15-40 nm. When bacon was fried on the gas or electric rings the particles were of larger diameter, in the size range 50-100 nm. The smaller particles generated during experiments grew in size with time because of coagulation. Substantial concentrations of NO, were generated during cooking on gas; four rings for 15 minutes produced 5 minute peaks of about 1000 ppb nitrogen dioxide and about 2000 ppb nitric oxide. Conclusions - Cooking in a poorly ventilated kitchen may give rise to potentially toxic concentrations of numbers of particles. Very high concentrations of oxides of nitrogen may also be generated by gas cooking, and with no extraction and poor ventilation, may reach concentrations at which adverse health effects may be expected. Although respiratory effects of exposure to NO, might be anticipated, recent epidemiology suggests that cardiac effects cannot be excluded, and further investigation of this is desirable.	46	131	2001	6	10.1136/oem.58.8.511	Public, Environmental & Occupational Health
"Threshold of toxicological concern for chemical substances present in the diet: A practical tool for assessing the need for toxicity testing. The de,minimis concept acknowledges a human exposure threshold value for chemicals below which there is no significant risk to human health. It is the underlying principle for the US Food and Drug Administration (FDA) regulation on substances used in food-contact articles. Further to this, the principle of Threshold of Toxicological Concern (TTC) has been developed and is now used by the joint FAO/WHO Expert Committee on Food Additives (JECFA) in their evaluations. Establishing an accepted TTC would benefit consumers, industry and regulators, since it would preclude extensive toxicity evaluations when Lumen intakes are below such threshold, and direct considerable time and cost resources towards testing substances with the highest potential risk to human health. It was questioned, however, whether specific endpoints that may potentially give rise to low-dose effects would be covered by such threshold. In this review., the possibility of defining a TTC for chemical substances present in the diet was examined for general toxicity endpoints (including carcinogenicity), as well as for specific endpoints, namely neurotoxicity and developmental neurotoxicity, immunotoxicity and developmental toxicity. For each of these endpoints, a database of specific no-observed-effect levels (NOELs) was compiled by screening oral toxicity studies. The substances recorded in each specific database were selected on the basis of their demonstrated adverse effects. For the neurotoxicity and developmental neurotoxicity databases, it was intended to cover all classes of compounds reported to hare tither a demonstrated neurotoxic or developmentally neurotoxic effect, or at least, on a biochemical or pharmacological basis were considered to have a potential for displaying such effects. For the immunotoxicity endpoint, it was ensured that only immunotoxicants were included in the database by selecting most of the substances from the Luster er al. database, provided that they satisfied the criteria for immunotoxicity defined by Luster. For the developmental toxicity database, substances were selected from the Munro ct nl. database that contained the lowest NOELs retrieved from the literature for more than 600 compounds. After screening these, substances shelving any effect which could point to developmental toxicity as broadly defined by the US EPA (1986) were recorded in the database. Additionally., endocrine toxicity and allergenicity, were addressed as two separate cases, using different approaches and methodology. The distributions of NOELs for the neurotoxicity, developmental neurotoxicity and developmental toxicity endpoints were compared with the distribution of NOELs for non-specific carcinogenic endpoints. As the immunotoxicity database was too limited to draw such a distribution of immune NOELs, the immunotoxicity endpoint,vas evaluated by comparing immune NOELs (or LOELs-lowest-observed-effect levels-when NOELs were not available),vith non-immune NOELs (or LOELs), in order to compare the sensitivity of this endpoint with non-specific endpoints. A different methodology was adopted for the evaluation of the endocrine toxicity endpoint since data currently available do not permit the establishment of a clear causal link between endocrine active chemicals and adverse effects in humans. Therefore, this endpoint was analysed by estimating the human exposure to oestrogenic environmental chemicals and evaluating their potential impact on human health, based on their contribution to the overall exposure, and their estrogenic potency relative to endogenous hormones. The allergenicity endpoint was not analysed as such. It was addressed in a separate section because this issue is not relevant to the overall population but rather to subsets of susceptible individuals, and allergic risks are usually controlled by other means (i.e, labelling) than the Threshold of Toxicological Concern approach. However, as several researchers are currently examining the existence of a threshold in allergy, the possibility of determining threshold doses for food allergens was put into perspective, and the likelihood for chemical substances to induce allergy at dietary relevant doses was discussed. The analysis indicated that, within the limitation of the databases, developmental neurotoxicity and developmental toxicity were not more sensitive than other non-specific endpoints. Although the cumulative distribution of NOELs for neurotoxic compounds was significantly loner than those for other non-cancer endpoints, these substances were accommodated within the TTC of 1.5 mu g/person/day. Furthermore, the analysis demonstrated that none of the specific non-cancer endpoints evaluated in the present study was more sensitive than cancer and, that a TTC of 1.5 mu g/person/day based on cancer endpoints provides an adequate margin of safety. Analysis of the immunotoxicity database should that for the group of immunotoxicants examined here, the specific immunotoxic endpoint was not more sensitive than other endpoints. In other words, the distribution of immunotoxic NOELs for these compounds did not appear to differ from the distribution of nonspecific endpoints NOELs for the same compounds. The dietary intakes of environmental oestrogenic chemicals were estimated and their oestrogenic potencies were compared with that of endogenous hormones, in order to assess their impact on human health. The results are in line with scientific data obtained so far, suggesting that estrogenic compounds of anthropogenic origin, in comparison with endogenous hormones, possess only little hormonal activity lilts phytoestrogens. Results of animal studies do not suggest that hormonal effects are to be expected from the rather lon concentrations found in foods. More data are necessary to determine threshold doses for food allergens. However, provided that numerous criteria need to be satisfied before sensitization occurs, it is unlikely that small molecules used in little amounts in foods would induce such reactions. On the basis of the present analysis, which was conducted using conservative assumptions at each step of the procedure (i.e. in data compilation and data analysis), and continually adopting a ""worst case"" perspective, it can be concluded that a Threshold of Toxicological Concern of 1.5 mu g/person/day provides adequate safety assurance. Chemical substances present in the diet that are consumed at levels below this threshold pose no appreciable risk. Moreover, for compounds which do not possess structural alerts for genotoxicity and carcinogenicity, further analysis mag indicate that a higher Threshold of Toxicological Concern mag he appropriate. (C) 2000 Elsevier in Science Ltd. All rights reserved.. threshold| toxicological endpoints| structural alerts| noel|developmental neurotoxicity evaluation| carcinogenic potency database| acoustic startle response| noncancer risk assessment| estrogen-receptor-beta| perinatal pcb exposure| breast-cancer cells| sprague-dawley rats| female b6c3f1 mice| prenatal exposure."	FEB-MAR-2000	threshold| toxicological endpoints| structural alerts| noel|developmental neurotoxicity evaluation| carcinogenic potency database| acoustic startle response| noncancer risk assessment| estrogen-receptor-beta| perinatal pcb exposure| breast-cancer cells| sprague-dawley rats| female b6c3f1 mice| prenatal exposure	Kroes, R; Galli, C; Munro, I; Schilter, B; Tran, LA; Walker, R; Wurtzen, G	Threshold of toxicological concern for chemical substances present in the diet: A practical tool for assessing the need for toxicity testing		FOOD AND CHEMICAL TOXICOLOGY	threshold; toxicological endpoints; structural alerts; NOEL	DEVELOPMENTAL NEUROTOXICITY EVALUATION; CARCINOGENIC POTENCY DATABASE; ACOUSTIC STARTLE RESPONSE; NONCANCER RISK ASSESSMENT; ESTROGEN-RECEPTOR-BETA; PERINATAL PCB EXPOSURE; BREAST-CANCER CELLS; SPRAGUE-DAWLEY RATS; FEMALE B6C3F1 MICE; PRENATAL EXPOSURE	"The de,minimis concept acknowledges a human exposure threshold value for chemicals below which there is no significant risk to human health. It is the underlying principle for the US Food and Drug Administration (FDA) regulation on substances used in food-contact articles. Further to this, the principle of Threshold of Toxicological Concern (TTC) has been developed and is now used by the joint FAO/WHO Expert Committee on Food Additives (JECFA) in their evaluations. Establishing an accepted TTC would benefit consumers, industry and regulators, since it would preclude extensive toxicity evaluations when Lumen intakes are below such threshold, and direct considerable time and cost resources towards testing substances with the highest potential risk to human health. It was questioned, however, whether specific endpoints that may potentially give rise to low-dose effects would be covered by such threshold. In this review., the possibility of defining a TTC for chemical substances present in the diet was examined for general toxicity endpoints (including carcinogenicity), as well as for specific endpoints, namely neurotoxicity and developmental neurotoxicity, immunotoxicity and developmental toxicity. For each of these endpoints, a database of specific no-observed-effect levels (NOELs) was compiled by screening oral toxicity studies. The substances recorded in each specific database were selected on the basis of their demonstrated adverse effects. For the neurotoxicity and developmental neurotoxicity databases, it was intended to cover all classes of compounds reported to hare tither a demonstrated neurotoxic or developmentally neurotoxic effect, or at least, on a biochemical or pharmacological basis were considered to have a potential for displaying such effects. For the immunotoxicity endpoint, it was ensured that only immunotoxicants were included in the database by selecting most of the substances from the Luster er al. database, provided that they satisfied the criteria for immunotoxicity defined by Luster. For the developmental toxicity database, substances were selected from the Munro ct nl. database that contained the lowest NOELs retrieved from the literature for more than 600 compounds. After screening these, substances shelving any effect which could point to developmental toxicity as broadly defined by the US EPA (1986) were recorded in the database. Additionally., endocrine toxicity and allergenicity, were addressed as two separate cases, using different approaches and methodology. The distributions of NOELs for the neurotoxicity, developmental neurotoxicity and developmental toxicity endpoints were compared with the distribution of NOELs for non-specific carcinogenic endpoints. As the immunotoxicity database was too limited to draw such a distribution of immune NOELs, the immunotoxicity endpoint,vas evaluated by comparing immune NOELs (or LOELs-lowest-observed-effect levels-when NOELs were not available),vith non-immune NOELs (or LOELs), in order to compare the sensitivity of this endpoint with non-specific endpoints. A different methodology was adopted for the evaluation of the endocrine toxicity endpoint since data currently available do not permit the establishment of a clear causal link between endocrine active chemicals and adverse effects in humans. Therefore, this endpoint was analysed by estimating the human exposure to oestrogenic environmental chemicals and evaluating their potential impact on human health, based on their contribution to the overall exposure, and their estrogenic potency relative to endogenous hormones. The allergenicity endpoint was not analysed as such. It was addressed in a separate section because this issue is not relevant to the overall population but rather to subsets of susceptible individuals, and allergic risks are usually controlled by other means (i.e, labelling) than the Threshold of Toxicological Concern approach. However, as several researchers are currently examining the existence of a threshold in allergy, the possibility of determining threshold doses for food allergens was put into perspective, and the likelihood for chemical substances to induce allergy at dietary relevant doses was discussed. The analysis indicated that, within the limitation of the databases, developmental neurotoxicity and developmental toxicity were not more sensitive than other non-specific endpoints. Although the cumulative distribution of NOELs for neurotoxic compounds was significantly loner than those for other non-cancer endpoints, these substances were accommodated within the TTC of 1.5 mu g/person/day. Furthermore, the analysis demonstrated that none of the specific non-cancer endpoints evaluated in the present study was more sensitive than cancer and, that a TTC of 1.5 mu g/person/day based on cancer endpoints provides an adequate margin of safety. Analysis of the immunotoxicity database should that for the group of immunotoxicants examined here, the specific immunotoxic endpoint was not more sensitive than other endpoints. In other words, the distribution of immunotoxic NOELs for these compounds did not appear to differ from the distribution of nonspecific endpoints NOELs for the same compounds. The dietary intakes of environmental oestrogenic chemicals were estimated and their oestrogenic potencies were compared with that of endogenous hormones, in order to assess their impact on human health. The results are in line with scientific data obtained so far, suggesting that estrogenic compounds of anthropogenic origin, in comparison with endogenous hormones, possess only little hormonal activity lilts phytoestrogens. Results of animal studies do not suggest that hormonal effects are to be expected from the rather lon concentrations found in foods. More data are necessary to determine threshold doses for food allergens. However, provided that numerous criteria need to be satisfied before sensitization occurs, it is unlikely that small molecules used in little amounts in foods would induce such reactions. On the basis of the present analysis, which was conducted using conservative assumptions at each step of the procedure (i.e. in data compilation and data analysis), and continually adopting a ""worst case"" perspective, it can be concluded that a Threshold of Toxicological Concern of 1.5 mu g/person/day provides adequate safety assurance. Chemical substances present in the diet that are consumed at levels below this threshold pose no appreciable risk. Moreover, for compounds which do not possess structural alerts for genotoxicity and carcinogenicity, further analysis mag indicate that a higher Threshold of Toxicological Concern mag he appropriate. (C) 2000 Elsevier in Science Ltd. All rights reserved."	267	131	2000	58	10.1016/S0278-6915(99)00120-9	Food Science & Technology; Toxicology
Prolonged allergen exposure induces structural airway changes in sensitized rats. The pathogenesis and functional consequences of airway remodeling in asthma remain to be fully established. In the present study we evaluated the effect of prolonged allergen exposure on airway function and structure in rats. Sensitized Brown Norway rats were repeatedly exposed for periods of 2 4, or 12 wk to aerosolized ovalbumin (OA) or phosphate-buffered saline (PBS). OA exposure induced a persistent increase in OA-specific serum IgE and in the number of peribronchial eosinophils. After 2 wk of OA exposure, airway histology revealed goblet-cell hyperplasia, an increase in bromodeoxyuridine-positive cells in airway epithelium, increased fibronectin deposition, and a thickening of the airway inner wall area. This coincided with airway hyperresponsiveness (AHR) to aerosolized carbachol. After OA exposure for 12 wk, increased fibronectin (p < 0.05 versus PBS) and collagen deposition (p < 0.05 versus PBS) were observed in the submucosa. After 12 wk of exposure, neither total nor inner wall area or airway responsiveness to carbachol were any longer significantly different from those of PBS-exposed animals. In conclusion, prolonged OA exposure in rats induces structural airway changes that bear similarities to airway remodeling in asthma. The study data further indicate that depending on the extent and distribution of remodeling, changes in the extracellular matrix can enhance or protect against AHR.. smooth-muscle cells| brown-norway rats| chronic-bronchitis| antigen challenge| asthma| expression| fibronectin| responsiveness| proliferation| methacholine.	FEB-2000	smooth-muscle cells| brown-norway rats| chronic-bronchitis| antigen challenge| asthma| expression| fibronectin| responsiveness| proliferation| methacholine	Palmans, E; Kips, JC; Pauwels, RA	Prolonged allergen exposure induces structural airway changes in sensitized rats		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		SMOOTH-MUSCLE CELLS; BROWN-NORWAY RATS; CHRONIC-BRONCHITIS; ANTIGEN CHALLENGE; ASTHMA; EXPRESSION; FIBRONECTIN; RESPONSIVENESS; PROLIFERATION; METHACHOLINE	The pathogenesis and functional consequences of airway remodeling in asthma remain to be fully established. In the present study we evaluated the effect of prolonged allergen exposure on airway function and structure in rats. Sensitized Brown Norway rats were repeatedly exposed for periods of 2 4, or 12 wk to aerosolized ovalbumin (OA) or phosphate-buffered saline (PBS). OA exposure induced a persistent increase in OA-specific serum IgE and in the number of peribronchial eosinophils. After 2 wk of OA exposure, airway histology revealed goblet-cell hyperplasia, an increase in bromodeoxyuridine-positive cells in airway epithelium, increased fibronectin deposition, and a thickening of the airway inner wall area. This coincided with airway hyperresponsiveness (AHR) to aerosolized carbachol. After OA exposure for 12 wk, increased fibronectin (p < 0.05 versus PBS) and collagen deposition (p < 0.05 versus PBS) were observed in the submucosa. After 12 wk of exposure, neither total nor inner wall area or airway responsiveness to carbachol were any longer significantly different from those of PBS-exposed animals. In conclusion, prolonged OA exposure in rats induces structural airway changes that bear similarities to airway remodeling in asthma. The study data further indicate that depending on the extent and distribution of remodeling, changes in the extracellular matrix can enhance or protect against AHR.	36	131	2000	9		General & Internal Medicine; Respiratory System
Twenty years of telemedicine in chronic disease management - an evidence synthesis. A literature review was conducted to obtain a high-level view of the value of telemedicine in the management of five common chronic diseases (asthma, COPD, diabetes, heart failure, hypertension). A total of 141 randomised controlled trials (RCTs) was identified, in which 148 telemedicine interventions of various kinds had been tested in a total of 37,695 patients. The value of each intervention was categorised in terms of the outcomes specified by the investigators in that trial, i.e. no attempt was made to extract a common outcome from all studies, as would be required for a conventional meta-analysis. Summarizing the value of these interventions shows, first, that most studies have reported positive effects (n = 108), and almost none have reported negative effects (n = 2). This suggests publication bias. Second, there were no significant differences between the chronic diseases, i.e. telemedicine seems equally effective (or ineffective) in the diseases studied. Third, most studies have been relatively short-term (median duration 6 months). It seems unlikely that in a chronic disease, any intervention can have much effect unless applied for a long period. Finally, there have been very few studies of cost-effectiveness. Thus the evidence base for the value of telemedicine in managing chronic diseases is on the whole weak and contradictory.. obstructive pulmonary-disease| congestive-heart-failure| of-the-literature| home telehealth| diabetes management| metaanalysis| care| interventions| support| burden.	2012	obstructive pulmonary-disease| congestive-heart-failure| of-the-literature| home telehealth| diabetes management| metaanalysis| care| interventions| support| burden	Wootton, R	Twenty years of telemedicine in chronic disease management - an evidence synthesis		JOURNAL OF TELEMEDICINE AND TELECARE		OBSTRUCTIVE PULMONARY-DISEASE; CONGESTIVE-HEART-FAILURE; OF-THE-LITERATURE; HOME TELEHEALTH; DIABETES MANAGEMENT; METAANALYSIS; CARE; INTERVENTIONS; SUPPORT; BURDEN	A literature review was conducted to obtain a high-level view of the value of telemedicine in the management of five common chronic diseases (asthma, COPD, diabetes, heart failure, hypertension). A total of 141 randomised controlled trials (RCTs) was identified, in which 148 telemedicine interventions of various kinds had been tested in a total of 37,695 patients. The value of each intervention was categorised in terms of the outcomes specified by the investigators in that trial, i.e. no attempt was made to extract a common outcome from all studies, as would be required for a conventional meta-analysis. Summarizing the value of these interventions shows, first, that most studies have reported positive effects (n = 108), and almost none have reported negative effects (n = 2). This suggests publication bias. Second, there were no significant differences between the chronic diseases, i.e. telemedicine seems equally effective (or ineffective) in the diseases studied. Third, most studies have been relatively short-term (median duration 6 months). It seems unlikely that in a chronic disease, any intervention can have much effect unless applied for a long period. Finally, there have been very few studies of cost-effectiveness. Thus the evidence base for the value of telemedicine in managing chronic diseases is on the whole weak and contradictory.	34	130	2012	10	10.1258/jtt.2012.120219	Health Care Sciences & Services
Acute Effects of Air Pollution on Pulmonary Function, Airway Inflammation, and Oxidative Stress in Asthmatic Children. BACKGROUND: Air pollution is associated with respiratory symptoms, lung function decrements, and hospitalizations. However, there is little information about the influence of air pollution on lung injury. OBJECTIVE: In this study we investigated acute effects of air pollution on pulmonary function and airway oxidative stress and inflammation in asthmatic children. METHODS: We studied 182 children with asthma, 9-14 years of age, for 4 weeks. Daily ambient concentrations of sulfur dioxide, nitrogen dioxide, ozone, and particulate matter <= 2.5 mu m in aerodynamic diameter (PM(2.5)) were monitored from two stations. Once a week we measured spirometry and fractional exhaled nitric oxide (Fe(NO)), and determined thiobarbituric acid reactive substances (TBARS) and 8-isoprostane-two oxidative stress markers-and interieukin-6 (IL-6) in breath condensate. We tested associations using mixed-effects regression models, adjusting for confounding variables. RESULTS: Interquartile-range increases in 3-day average SO(2) (5.4 ppb), NO(2) (6.8 ppb), and PM(2.5) (5.4 mu g/m(3)) were associated with decreases in forced expiratory flow between 25% and 75% of forced vital capacity, with changes being -3.1% [95% confidence interval (CI), -5.8 to -0.3), -2.8% (95% CI, -4.8 to -0.8), and -3.0% (95% CI, -4.7 to -1.2), respectively. SO(2), NO(2), and PM(2.5) were associated with increases in TBARS, with changes being 36.2% (95% CI, 15.7 to 57.2), 21.8% (95% CI, 8.2 to 36.0), and 24.8% (95% CI, 10.8 to 39.4), respectively. Risk estimates appear to be larger in children not taking corticosteroids than in children taking corticosteroids. O(3) (5.3 ppb) was not associated with health end points. Fe(NO), 8-isoprostane, and IL-6 were not associated with air pollutants. CONCLUSION: Air pollution may increase airway oxidative stress and decrease small airway function of asthmatic children. Inhaled corticosteroids may reduce oxidative stress and improve airway function.. air pollution| asthma| children| exhaled breath condensate| inflammation| oxidative stress| pulmonary function|exhaled breath condensate| nitric-oxide| thiobarbituric-acid| lipid-peroxidation| particulate matter| respiratory health| epithelial injury| in-vivo| exposure| 8-isoprostane.	APR-2009	air pollution| asthma| children| exhaled breath condensate| inflammation| oxidative stress| pulmonary function|exhaled breath condensate| nitric-oxide| thiobarbituric-acid| lipid-peroxidation| particulate matter| respiratory health| epithelial injury| in-vivo| exposure| 8-isoprostane	Liu, L; Poon, R; Chen, L; Frescura, AM; Montuschi, P; Ciabattoni, G; Wheeler, A; Dales, R	Acute Effects of Air Pollution on Pulmonary Function, Airway Inflammation, and Oxidative Stress in Asthmatic Children		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma; children; exhaled breath condensate; inflammation; oxidative stress; pulmonary function	EXHALED BREATH CONDENSATE; NITRIC-OXIDE; THIOBARBITURIC-ACID; LIPID-PEROXIDATION; PARTICULATE MATTER; RESPIRATORY HEALTH; EPITHELIAL INJURY; IN-VIVO; EXPOSURE; 8-ISOPROSTANE	BACKGROUND: Air pollution is associated with respiratory symptoms, lung function decrements, and hospitalizations. However, there is little information about the influence of air pollution on lung injury. OBJECTIVE: In this study we investigated acute effects of air pollution on pulmonary function and airway oxidative stress and inflammation in asthmatic children. METHODS: We studied 182 children with asthma, 9-14 years of age, for 4 weeks. Daily ambient concentrations of sulfur dioxide, nitrogen dioxide, ozone, and particulate matter <= 2.5 mu m in aerodynamic diameter (PM(2.5)) were monitored from two stations. Once a week we measured spirometry and fractional exhaled nitric oxide (Fe(NO)), and determined thiobarbituric acid reactive substances (TBARS) and 8-isoprostane-two oxidative stress markers-and interieukin-6 (IL-6) in breath condensate. We tested associations using mixed-effects regression models, adjusting for confounding variables. RESULTS: Interquartile-range increases in 3-day average SO(2) (5.4 ppb), NO(2) (6.8 ppb), and PM(2.5) (5.4 mu g/m(3)) were associated with decreases in forced expiratory flow between 25% and 75% of forced vital capacity, with changes being -3.1% [95% confidence interval (CI), -5.8 to -0.3), -2.8% (95% CI, -4.8 to -0.8), and -3.0% (95% CI, -4.7 to -1.2), respectively. SO(2), NO(2), and PM(2.5) were associated with increases in TBARS, with changes being 36.2% (95% CI, 15.7 to 57.2), 21.8% (95% CI, 8.2 to 36.0), and 24.8% (95% CI, 10.8 to 39.4), respectively. Risk estimates appear to be larger in children not taking corticosteroids than in children taking corticosteroids. O(3) (5.3 ppb) was not associated with health end points. Fe(NO), 8-isoprostane, and IL-6 were not associated with air pollutants. CONCLUSION: Air pollution may increase airway oxidative stress and decrease small airway function of asthmatic children. Inhaled corticosteroids may reduce oxidative stress and improve airway function.	51	130	2009	7	10.1289/ehp11813	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Correlation of nitrogen dioxide with other traffic pollutants near a major expressway. Objectives: This study addresses three objectives: (1) to assess the correlation of NO2 to other ambient pollutants measured with passive samplers; (2) to explore peak traffic particulate matter air pollution correlations with passively measured NO2; and (3) to pilot an advanced mobile air pollution laboratory to supply supplementary information on correlations between NO2 and other air pollutants. Methods: Active and passive monitoring was conducted at two transects perpendicular to an expressway with nearly 400,000 vehicles per day. NO2, NOx, O-3, VOCs, fine-particles and ultrafine particles were measured at increasing distance away from the expressway. The measurement equipment included Ogawa, TraceAir and 3 M organic vapor monitors (OVM-3500) passive samplers, and an array of active measurement equipment: Dust-Trak and P-Trak monitors, chemoluminescent analyzer, aethalometer, tapered element oscillating microbalance, Grimm condensation particle counter, and an lonicon analytik proton transfer reaction mass spectrometer. Results: Levels of NO2 were observed to decay with increasing distance from the expressway, declining to background levels by 300 m. Moderate to high correlations were observed between passive NO2 measurements and passive NOx, O-3 (r similar to 0.60-0.86). The correlations with active PM measurements made with Dust-Trak and P-Trak monitors were in the range 0.64-0.78; correlations between NO2 and VOCs were more variable. Active measurements of NO2 and PM2.5, ultrafine particles, O-3 and black carbon, had high correlations (r similar to 0.7-0.96). Discussion: The variability of many traffic-related pollutants around an expressway is characterized well by passive measurements of NO2. Further research is needed to assess whether these relationships hold in different traffic and land-use environments. (c) 2007 Elsevier Ltd. All rights reserved.. traffic| air pollution| no2| voc| fine particulate matter| ultrafine particles| toronto| distance decay|air-pollution| ultrafine particles| pm2.5 concentrations| highway| indoor| road| exposure| children| outdoor| asthma.	JAN-2008	traffic| air pollution| no2| voc| fine particulate matter| ultrafine particles| toronto| distance decay|air-pollution| ultrafine particles| pm2.5 concentrations| highway| indoor| road| exposure| children| outdoor| asthma	Beckerman, B; Jerrett, M; Brook, JR; Verma, DK; Arain, MA; Finkelstein, MM	Correlation of nitrogen dioxide with other traffic pollutants near a major expressway		ATMOSPHERIC ENVIRONMENT	traffic; air pollution; NO2; VOC; fine particulate matter; ultrafine particles; Toronto; distance decay	AIR-POLLUTION; ULTRAFINE PARTICLES; PM2.5 CONCENTRATIONS; HIGHWAY; INDOOR; ROAD; EXPOSURE; CHILDREN; OUTDOOR; ASTHMA	Objectives: This study addresses three objectives: (1) to assess the correlation of NO2 to other ambient pollutants measured with passive samplers; (2) to explore peak traffic particulate matter air pollution correlations with passively measured NO2; and (3) to pilot an advanced mobile air pollution laboratory to supply supplementary information on correlations between NO2 and other air pollutants. Methods: Active and passive monitoring was conducted at two transects perpendicular to an expressway with nearly 400,000 vehicles per day. NO2, NOx, O-3, VOCs, fine-particles and ultrafine particles were measured at increasing distance away from the expressway. The measurement equipment included Ogawa, TraceAir and 3 M organic vapor monitors (OVM-3500) passive samplers, and an array of active measurement equipment: Dust-Trak and P-Trak monitors, chemoluminescent analyzer, aethalometer, tapered element oscillating microbalance, Grimm condensation particle counter, and an lonicon analytik proton transfer reaction mass spectrometer. Results: Levels of NO2 were observed to decay with increasing distance from the expressway, declining to background levels by 300 m. Moderate to high correlations were observed between passive NO2 measurements and passive NOx, O-3 (r similar to 0.60-0.86). The correlations with active PM measurements made with Dust-Trak and P-Trak monitors were in the range 0.64-0.78; correlations between NO2 and VOCs were more variable. Active measurements of NO2 and PM2.5, ultrafine particles, O-3 and black carbon, had high correlations (r similar to 0.7-0.96). Discussion: The variability of many traffic-related pollutants around an expressway is characterized well by passive measurements of NO2. Further research is needed to assess whether these relationships hold in different traffic and land-use environments. (c) 2007 Elsevier Ltd. All rights reserved.	30	130	2008	16	10.1016/j.atmosenv.2007.09.042	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Common characteristics of upper and lower airways in rhinitis and asthma: ARIA update, in collaboration with GA(2)LEN. This update aimed to review the new evidence available to support or refute prior Allergic Rhinitis and its Impact on Asthma (ARIA) statements. A Medline search of publications between 2000 and 2005 was conducted, with articles selected by experts. New evidence supports previous ARIA statements, such as: (i) allergic rhinitis (AR) is a risk factor for asthma; (ii) patients with persistent rhinitis should be evaluated for asthma; (iii) most patients with asthma have rhinitis; (iv) a combined strategy should be used to treat the airways and (v) in low- to middle-income countries, a different strategy may be needed. The increased risk of asthma has also been found among sufferers from non-AR. Recent reports show AR is a global problem. Many studies demonstrated parallel increasing prevalence of asthma and rhinitis, but in regions of highest prevalence, it may be reaching a plateau. Factors associated with a reduced risk of asthma and AR have been identified, confirming previous findings of protection related to exposure to infections. Treatment of rhinitis with intranasal glucocorticosteroids, antihistamines, leukotriene antagonists or immunotherapy may reduce morbidity because of asthma. To take advantage of the paradigm of unified airways, there is a need to rationalize diagnosis and treatment to optimize management.. allergy| asthma| atopy| review| rhinitis|seasonal allergic rhinitis| exhaled nitric-oxide| independent risk-factor| primary-school children| adult-onset asthma| quality-of-life| in-house dust| hay-fever| bronchial hyperresponsiveness| atopic eczema.	NOV-2007	allergy| asthma| atopy| review| rhinitis|seasonal allergic rhinitis| exhaled nitric-oxide| independent risk-factor| primary-school children| adult-onset asthma| quality-of-life| in-house dust| hay-fever| bronchial hyperresponsiveness| atopic eczema	Cruz, AA; Popov, T; Pawankar, R; Annesi-Maesano, I; Fokkens, W; Kemp, J; Ohta, K; Price, D; Bousquet, J	Common characteristics of upper and lower airways in rhinitis and asthma: ARIA update, in collaboration with GA(2)LEN		ALLERGY	allergy; asthma; atopy; review; rhinitis	SEASONAL ALLERGIC RHINITIS; EXHALED NITRIC-OXIDE; INDEPENDENT RISK-FACTOR; PRIMARY-SCHOOL CHILDREN; ADULT-ONSET ASTHMA; QUALITY-OF-LIFE; IN-HOUSE DUST; HAY-FEVER; BRONCHIAL HYPERRESPONSIVENESS; ATOPIC ECZEMA	This update aimed to review the new evidence available to support or refute prior Allergic Rhinitis and its Impact on Asthma (ARIA) statements. A Medline search of publications between 2000 and 2005 was conducted, with articles selected by experts. New evidence supports previous ARIA statements, such as: (i) allergic rhinitis (AR) is a risk factor for asthma; (ii) patients with persistent rhinitis should be evaluated for asthma; (iii) most patients with asthma have rhinitis; (iv) a combined strategy should be used to treat the airways and (v) in low- to middle-income countries, a different strategy may be needed. The increased risk of asthma has also been found among sufferers from non-AR. Recent reports show AR is a global problem. Many studies demonstrated parallel increasing prevalence of asthma and rhinitis, but in regions of highest prevalence, it may be reaching a plateau. Factors associated with a reduced risk of asthma and AR have been identified, confirming previous findings of protection related to exposure to infections. Treatment of rhinitis with intranasal glucocorticosteroids, antihistamines, leukotriene antagonists or immunotherapy may reduce morbidity because of asthma. To take advantage of the paradigm of unified airways, there is a need to rationalize diagnosis and treatment to optimize management.	196	130	2007	41	10.1111/j.1398-9995.2007.01551.x	Allergy; Immunology
The Canadian childhood asthma primary prevention study: Outcomes at 7 years of age. Background: Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development. Objective: The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age. Methods: Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacboline inhalation tests, and allergy skin tests. Results: At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71).. asthma| primary prevention|fatty-acid modification| allergen avoidance| bronchial hyperresponsiveness| house-dust| infancy| children| reactivity| symptoms| atopy.	JUL-2005	asthma| primary prevention|fatty-acid modification| allergen avoidance| bronchial hyperresponsiveness| house-dust| infancy| children| reactivity| symptoms| atopy	Chan-Yeung, M; Ferguson, A; Watson, W; Dimich-Ward, H; Rousseau, R; Lilley, M; DyBuncio, A; Becker, A	The Canadian childhood asthma primary prevention study: Outcomes at 7 years of age		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; primary prevention	FATTY-ACID MODIFICATION; ALLERGEN AVOIDANCE; BRONCHIAL HYPERRESPONSIVENESS; HOUSE-DUST; INFANCY; CHILDREN; REACTIVITY; SYMPTOMS; ATOPY	Background: Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development. Objective: The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age. Methods: Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacboline inhalation tests, and allergy skin tests. Results: At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71).	17	130	2005	7	10.1016/j.jaci.2005.03.029	Allergy; Immunology
T cell vaccination in mice with invasive pulmonary aspergillosis. Aspergillus fumigatus, an opportunistic fungal pathogen, is responsible for multiple airway diseases of an allergic and a nonallergic nature. In a murine model of invasive pulmonary aspergillosis, resistance is associated with a decreased lung inflammatory pathology and the occurrence of an IL-12-dependent Th1-type reactivity that are both impaired by IL-4, In the present study we assess the ability of Aspergillus crude culture filtrate Ags and the recombinant allergen Asp f 2 to induce protective antifungal responses in mice with invasive pulmonary aspergillosis, Similar to what occurred upon nasal exposure to viable A. fumigatus conidia, treatment of immunocompetent mice with Aspergillus crude culture filtrate Ags resulted in the development of local and peripheral protective Th1 memory responses, mediated by Ag-specific CD4(+) T cells producing IFN-gamma and IL-2 capable of conferring protection upon adoptive transfer to naive recipients. Protective Th1 responses could not be observed in mice deficient of IFN-gamma or IL-12 and did not occur in response to Asp f 2, which, on the contrary, elicited high level production of inhibitory IL-4. The results show that Ags of Aspergillus exist with the ability to induce both Th1- and Th2-type reactivity during infection, a finding that suggests a possible mechanism through which potentially protective immune responses are inhibited in mice with the infection. However, the occurrence of Th1-mediated resistance upon vaccination with Aspergillus crude culture filtrate Ags, suggests the existence of fungal Ags useful as a candidate vaccine against invasive pulmonary aspergillosis.. allergic bronchopulmonary aspergillosis| chronic granulomatous-disease| human-immunodeficiency-virus| candida-albicans infection| lung dendritic cells| host-defense| murine aspergillosis| antifungal activity| mucosal immunity| major allergen.	JUL 1-2000	allergic bronchopulmonary aspergillosis| chronic granulomatous-disease| human-immunodeficiency-virus| candida-albicans infection| lung dendritic cells| host-defense| murine aspergillosis| antifungal activity| mucosal immunity| major allergen	Cenci, E; Mencacci, A; Bacci, A; Bistoni, F; Kurup, VP; Romani, L	T cell vaccination in mice with invasive pulmonary aspergillosis		JOURNAL OF IMMUNOLOGY		ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; CHRONIC GRANULOMATOUS-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; CANDIDA-ALBICANS INFECTION; LUNG DENDRITIC CELLS; HOST-DEFENSE; MURINE ASPERGILLOSIS; ANTIFUNGAL ACTIVITY; MUCOSAL IMMUNITY; MAJOR ALLERGEN	Aspergillus fumigatus, an opportunistic fungal pathogen, is responsible for multiple airway diseases of an allergic and a nonallergic nature. In a murine model of invasive pulmonary aspergillosis, resistance is associated with a decreased lung inflammatory pathology and the occurrence of an IL-12-dependent Th1-type reactivity that are both impaired by IL-4, In the present study we assess the ability of Aspergillus crude culture filtrate Ags and the recombinant allergen Asp f 2 to induce protective antifungal responses in mice with invasive pulmonary aspergillosis, Similar to what occurred upon nasal exposure to viable A. fumigatus conidia, treatment of immunocompetent mice with Aspergillus crude culture filtrate Ags resulted in the development of local and peripheral protective Th1 memory responses, mediated by Ag-specific CD4(+) T cells producing IFN-gamma and IL-2 capable of conferring protection upon adoptive transfer to naive recipients. Protective Th1 responses could not be observed in mice deficient of IFN-gamma or IL-12 and did not occur in response to Asp f 2, which, on the contrary, elicited high level production of inhibitory IL-4. The results show that Ags of Aspergillus exist with the ability to induce both Th1- and Th2-type reactivity during infection, a finding that suggests a possible mechanism through which potentially protective immune responses are inhibited in mice with the infection. However, the occurrence of Th1-mediated resistance upon vaccination with Aspergillus crude culture filtrate Ags, suggests the existence of fungal Ags useful as a candidate vaccine against invasive pulmonary aspergillosis.	72	130	2000	8		Immunology
Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D. Muscarinic cholinergic signaling plays an essential role in the control of the normal airway functions and in the development of pulmonary pathologies including asthma. In this paper we demonstrate that the airways of mice deficient in a cAMP-specific phosphodiesterase (PDE4D) are no longer responsive to cholinergic stimulation. Airway hyperreactivity that follows exposure to antigen was also abolished in PDE4D(-/-) mice, despite an apparently normal lung inflammatory infiltration. The loss of cholinergic responsiveness was specific to the airway, not observed in the heart, and was associated with a loss of signaling through muscarinic receptors with an inability to decrease cAMP accumulation. These findings demonstrate that the PDE4D gene plays an essential role in cAMP homeostasis and cholinergic stimulation of the airway, and in the development of hyperreactivity. In view of the therapeutic potentials of PDE4 inhibitors, our findings provide the rationale for novel strategies that target a single PDE isoenzyme.. beta(2)-adrenergic receptor| selective-inhibition| atopic-dermatitis| smooth-muscle| rat-brain| t-cells| amp| identification| activation| asthma.	JUN 6-2000	beta(2)-adrenergic receptor| selective-inhibition| atopic-dermatitis| smooth-muscle| rat-brain| t-cells| amp| identification| activation| asthma	Hansen, G; Jin, SLC; Umetsu, DT; Conti, M	Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA		BETA(2)-ADRENERGIC RECEPTOR; SELECTIVE-INHIBITION; ATOPIC-DERMATITIS; SMOOTH-MUSCLE; RAT-BRAIN; T-CELLS; AMP; IDENTIFICATION; ACTIVATION; ASTHMA	Muscarinic cholinergic signaling plays an essential role in the control of the normal airway functions and in the development of pulmonary pathologies including asthma. In this paper we demonstrate that the airways of mice deficient in a cAMP-specific phosphodiesterase (PDE4D) are no longer responsive to cholinergic stimulation. Airway hyperreactivity that follows exposure to antigen was also abolished in PDE4D(-/-) mice, despite an apparently normal lung inflammatory infiltration. The loss of cholinergic responsiveness was specific to the airway, not observed in the heart, and was associated with a loss of signaling through muscarinic receptors with an inability to decrease cAMP accumulation. These findings demonstrate that the PDE4D gene plays an essential role in cAMP homeostasis and cholinergic stimulation of the airway, and in the development of hyperreactivity. In view of the therapeutic potentials of PDE4 inhibitors, our findings provide the rationale for novel strategies that target a single PDE isoenzyme.	44	130	2000	6	10.1073/pnas.97.12.6751	Science & Technology - Other Topics
Allergic contact dermatitis-formation, structural requirements, and reactivity of skin sensitizers. Contact allergy is caused by a wide range of chemicals after skin contact. Its clinical manifestation, allergic contact dermatitis (ACD), is developed upon repeated contact with the allergen. This perspective focuses on two areas that have yielded new useful information during the last 20 years: (i) structure-activity relationship (SAR) studies of contact allergy based on the concept of hapten-protein binding and (ii) mechanistic investigations regarding activation of nonsensitizing compounds to contact allergens by air oxidation or skin metabolism. The second area is more thoroughly reviewed since the full Picture has previously not been published. Prediction of the sensitizing capacity of a chemical is important to avoid outbreaks of ACD in the population. Much research has been devoted to the development of in vitro and in silico predictive testing methods. Today, no method exists that is sensitive enough to detect weak allergens and that is robust enough to be used for routine screening. To cause sensitization, a chemical C, must bind to macromolecules (proteins) in the skin, Expert systems containing information about the relationship between the chemical structure and the ability of chemicals to haptenate proteins are available. However, few designed SAR studies based on mechanistic investigations of prohaptens have been published. Many compounds are not allergenic themselves but are activated in the skin (e.g., metabolically) or before skin contact (e.g., via air oxidation) to form skin sensitizers. Thus, more basic research is needed on the chemical reactions involved in the antigen formation and the immunological mechanisms. The clinical importance of air oxidation to activate nonallergenic compounds has been demonstrated. Oxidized fragrance terpenes, in contrast to the pure terpenes, gave positive patch test reactions in consecutive dermatitis patients as frequently as the most common standard allergens. This shows the importance of using compounds to which people are exposed when screening for ACD in dermatology clinics.. lymph-node assay| oxidized d-limonene| mechanistic applicability domains| hepatic cytochrome-p450 enzymes| human dendritic cells| in-vitro| guinea-pig| 15-hydroperoxyabietic acid| oxidation-products| p-phenylenediamine.	JAN-2008	lymph-node assay| oxidized d-limonene| mechanistic applicability domains| hepatic cytochrome-p450 enzymes| human dendritic cells| in-vitro| guinea-pig| 15-hydroperoxyabietic acid| oxidation-products| p-phenylenediamine	Karlberg, AT; Bergstrom, MA; Borje, A; Luthman, K; Nilsson, JLG	Allergic contact dermatitis-formation, structural requirements, and reactivity of skin sensitizers		CHEMICAL RESEARCH IN TOXICOLOGY		LYMPH-NODE ASSAY; OXIDIZED D-LIMONENE; MECHANISTIC APPLICABILITY DOMAINS; HEPATIC CYTOCHROME-P450 ENZYMES; HUMAN DENDRITIC CELLS; IN-VITRO; GUINEA-PIG; 15-HYDROPEROXYABIETIC ACID; OXIDATION-PRODUCTS; P-PHENYLENEDIAMINE	Contact allergy is caused by a wide range of chemicals after skin contact. Its clinical manifestation, allergic contact dermatitis (ACD), is developed upon repeated contact with the allergen. This perspective focuses on two areas that have yielded new useful information during the last 20 years: (i) structure-activity relationship (SAR) studies of contact allergy based on the concept of hapten-protein binding and (ii) mechanistic investigations regarding activation of nonsensitizing compounds to contact allergens by air oxidation or skin metabolism. The second area is more thoroughly reviewed since the full Picture has previously not been published. Prediction of the sensitizing capacity of a chemical is important to avoid outbreaks of ACD in the population. Much research has been devoted to the development of in vitro and in silico predictive testing methods. Today, no method exists that is sensitive enough to detect weak allergens and that is robust enough to be used for routine screening. To cause sensitization, a chemical C, must bind to macromolecules (proteins) in the skin, Expert systems containing information about the relationship between the chemical structure and the ability of chemicals to haptenate proteins are available. However, few designed SAR studies based on mechanistic investigations of prohaptens have been published. Many compounds are not allergenic themselves but are activated in the skin (e.g., metabolically) or before skin contact (e.g., via air oxidation) to form skin sensitizers. Thus, more basic research is needed on the chemical reactions involved in the antigen formation and the immunological mechanisms. The clinical importance of air oxidation to activate nonallergenic compounds has been demonstrated. Oxidized fragrance terpenes, in contrast to the pure terpenes, gave positive patch test reactions in consecutive dermatitis patients as frequently as the most common standard allergens. This shows the importance of using compounds to which people are exposed when screening for ACD in dermatology clinics.	175	129	2008	17	10.1021/tx7002239	Pharmacology & Pharmacy; Chemistry; Toxicology
Severe exacerbations predict excess lung function decline in asthma. Severe asthma exacerbations are periods of intense airway inflammation that have been hypothesised to contribute to structural changes in the airways. If so, accelerated lung function decline over time should be more prevalent in adult patients with asthma who have frequent exacerbations than those without, but to date this has not been demonstrated. A cohort study was performed in order to investigate the effect of severe exacerbations on the progression of airway obstruction in 93 nonsmoking asthmatics with moderate-to-severe disease prior to treatment with inhaled corticosteroids. Subjects were followed for >= 5 yrs (median follow-up 11 yrs). In total, 56 (60.2%) subjects experienced at least one severe exacerbation (median rate 0.10.yr(-1)). Oral corticosteroid use and more severe airway obstruction at baseline were associated with a higher exacerbation rate. Independent of these variables, asthma patients with frequent exacerbations had a significantly larger annual decline in forced expiratory volume in one second (FEV1; median difference (95% confidence interval) 16.9 (1.5-32.2) mL.yr(-1)). Exacerbation rate significantly predicted an excess decline in FEV1, such that one severe exacerbation per year was associated with a 30.2 mL greater annual decline in FEV1. These data support the hypothesis that exacerbations, indicating intermittent periods of worsening airway inflammation, are associated with excess lung function decline in asthma.. airways remodelling| exacerbations| prognosis| treatment of asthma|air-flow obstruction| follow-up| general-population| corticosteroids| polymorphisms| limitation| disease| adults.	SEP-2007	airways remodelling| exacerbations| prognosis| treatment of asthma|air-flow obstruction| follow-up| general-population| corticosteroids| polymorphisms| limitation| disease| adults	Bai, TR; Vonk, JM; Postma, DS; Boezen, HM	Severe exacerbations predict excess lung function decline in asthma		EUROPEAN RESPIRATORY JOURNAL	airways remodelling; exacerbations; prognosis; treatment of asthma	AIR-FLOW OBSTRUCTION; FOLLOW-UP; GENERAL-POPULATION; CORTICOSTEROIDS; POLYMORPHISMS; LIMITATION; DISEASE; ADULTS	Severe asthma exacerbations are periods of intense airway inflammation that have been hypothesised to contribute to structural changes in the airways. If so, accelerated lung function decline over time should be more prevalent in adult patients with asthma who have frequent exacerbations than those without, but to date this has not been demonstrated. A cohort study was performed in order to investigate the effect of severe exacerbations on the progression of airway obstruction in 93 nonsmoking asthmatics with moderate-to-severe disease prior to treatment with inhaled corticosteroids. Subjects were followed for >= 5 yrs (median follow-up 11 yrs). In total, 56 (60.2%) subjects experienced at least one severe exacerbation (median rate 0.10.yr(-1)). Oral corticosteroid use and more severe airway obstruction at baseline were associated with a higher exacerbation rate. Independent of these variables, asthma patients with frequent exacerbations had a significantly larger annual decline in forced expiratory volume in one second (FEV1; median difference (95% confidence interval) 16.9 (1.5-32.2) mL.yr(-1)). Exacerbation rate significantly predicted an excess decline in FEV1, such that one severe exacerbation per year was associated with a 30.2 mL greater annual decline in FEV1. These data support the hypothesis that exacerbations, indicating intermittent periods of worsening airway inflammation, are associated with excess lung function decline in asthma.	22	129	2007	5	10.1183/09031936.00165106	Respiratory System
Association of FEV1 in asthmatic children with personal and microenvironmental exposure to airborne particulate matter. Exposure to particulate matter (PM) air pollution has been shown to exacerbate children's asthma, but the exposure sources and temporal characteristics are still under study. Children's exposure to PM is likely to involve both combustion-related ambient PM and PM related to a child's activity in various indoor and outdoor microenvironments. Among 19 children with asthma, 9-17 years of age, we examined the relationship of temporal changes in percent predicted forced expiratory volume in 1 sec (FEV1) to personal continuous PM exposure and to 24-hr average gravimetric PM mass measured at home and central sites. Subjects were followed for 2 weeks during either the fall of 1999 or the spring of 2000, in a southern California region affected by transported air pollution. FEV1 was measured by subjects in the morning, afternoon, and evening. Exposure measurements included continuous PM using a passive nephelometer carried by subjects; indoor, outdoor home, and central-site 24-hr gravimetric PM2.5 (PM of aerodynamic diameter < 2.5 mum) and PM10; and central-site hourly PM10, nitrogen dioxide, and ozone. Data were analyzed with linear mixed models controlling for within-subject autocorrelation, FEV1 maneuver time, and exposure period. We found inverse associations of FEV1 with increasing PM exposure during the 24 hr before the FEV1 maneuver and with increasing multiday PM averages. Deficits in percent predicted FEV1 (95% confidence interval) for given PM interquartile ranges measured during the preceding 24-hr were as follows: 128 mug/m(3) 1-hr maximum personal PM, -6.0% (-10.5 to -1.4); 30 mug/m(3) 24-hr average personal PM, -5.9% (-10.8 to -1.0); 6.7 mug/m(3) indoor home PM2.5, -1.6% (-2.8 to -0.4); 16 mug/m(3) indoor home PM10, -2.1% (-3.7 to -0.4); 7.1 mug/m(3) outdoor home PM2.5, -1-1% (-2.4 to 0.1); and 7.5 mug/m(3) central-site P-M2.5, -0.7% (-1.9 to 0.4). Stronger associations were found for multiday moving averages of PM for both personal and stationary-site PM. Stronger associations with personal PM were found in boys allergic to indoor allergens. FEV1 was weakly associated with NO2 but not with O-3. Results suggest mixed respiratory effects of PM in asthmatic children from both ambient background exposures and personal exposures in various microenvironments.. asthma| epidemiology| forced expiratory volume| longitudinal data analysis| nitrogen dioxide| ozone| panel study| particulate air pollution|antiinflammatory medication use| ambient air-pollution| inner-city children| respiratory health| symptom severity| particles| indoor| time| california| pollutants.	JUN-2004	asthma| epidemiology| forced expiratory volume| longitudinal data analysis| nitrogen dioxide| ozone| panel study| particulate air pollution|antiinflammatory medication use| ambient air-pollution| inner-city children| respiratory health| symptom severity| particles| indoor| time| california| pollutants	Delfino, RJ; Quintana, PJE; Floro, J; Gastanaga, VM; Samimi, BS; Kleinman, MT; Liu, LJS; Bufalino, C; Wu, CF; McLaren, CE	Association of FEV1 in asthmatic children with personal and microenvironmental exposure to airborne particulate matter		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; epidemiology; forced expiratory volume; longitudinal data analysis; nitrogen dioxide; ozone; panel study; particulate air pollution	ANTIINFLAMMATORY MEDICATION USE; AMBIENT AIR-POLLUTION; INNER-CITY CHILDREN; RESPIRATORY HEALTH; SYMPTOM SEVERITY; PARTICLES; INDOOR; TIME; CALIFORNIA; POLLUTANTS	Exposure to particulate matter (PM) air pollution has been shown to exacerbate children's asthma, but the exposure sources and temporal characteristics are still under study. Children's exposure to PM is likely to involve both combustion-related ambient PM and PM related to a child's activity in various indoor and outdoor microenvironments. Among 19 children with asthma, 9-17 years of age, we examined the relationship of temporal changes in percent predicted forced expiratory volume in 1 sec (FEV1) to personal continuous PM exposure and to 24-hr average gravimetric PM mass measured at home and central sites. Subjects were followed for 2 weeks during either the fall of 1999 or the spring of 2000, in a southern California region affected by transported air pollution. FEV1 was measured by subjects in the morning, afternoon, and evening. Exposure measurements included continuous PM using a passive nephelometer carried by subjects; indoor, outdoor home, and central-site 24-hr gravimetric PM2.5 (PM of aerodynamic diameter < 2.5 mum) and PM10; and central-site hourly PM10, nitrogen dioxide, and ozone. Data were analyzed with linear mixed models controlling for within-subject autocorrelation, FEV1 maneuver time, and exposure period. We found inverse associations of FEV1 with increasing PM exposure during the 24 hr before the FEV1 maneuver and with increasing multiday PM averages. Deficits in percent predicted FEV1 (95% confidence interval) for given PM interquartile ranges measured during the preceding 24-hr were as follows: 128 mug/m(3) 1-hr maximum personal PM, -6.0% (-10.5 to -1.4); 30 mug/m(3) 24-hr average personal PM, -5.9% (-10.8 to -1.0); 6.7 mug/m(3) indoor home PM2.5, -1.6% (-2.8 to -0.4); 16 mug/m(3) indoor home PM10, -2.1% (-3.7 to -0.4); 7.1 mug/m(3) outdoor home PM2.5, -1-1% (-2.4 to 0.1); and 7.5 mug/m(3) central-site P-M2.5, -0.7% (-1.9 to 0.4). Stronger associations were found for multiday moving averages of PM for both personal and stationary-site PM. Stronger associations with personal PM were found in boys allergic to indoor allergens. FEV1 was weakly associated with NO2 but not with O-3. Results suggest mixed respiratory effects of PM in asthmatic children from both ambient background exposures and personal exposures in various microenvironments.	51	129	2004	10	10.1289/ehp.6815	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Reported incidence of occupational asthma in France, 1996-99: the ONAP programme. Aims: To estimate the general and specific incidence of occupational asthma in France in 1996-99; and to describe the distribution of cases by age, sex, suspected causal agents, and occupation. Methods: New cases of occupational asthma were collected by a national surveillance programme, based on voluntary reporting, named Observatoire National des Asthmes Professionnels (ONAP), involving a network of occupational and chest physicians. For each case, the reporting form included information on age, sex, location of workplace, occupation, suspected causal agent, and methods of diagnosis. Estimates of the working population, used to calculate incidence rates by age, sex, region, and occupation, were obtained from the Institut National de la Statistique et des Etudes Economiques (INSEE) and from the French Securite Sociale statistics. Results: In 1996-99, 2178 cases of occupational asthma were reported to the ONAP, giving a mean annual rate of 24/million. Rates in men were higher than rates in women (27/million versus 19/million). The highest rate was observed in the 15-29 years age group (30/million). The most frequently incriminated agents were flour (20.3%), isocyanates (14.1%), latex (7.2%), aldehyde (5.9%), persulphate salts (5.8%), and wood dusts (3.7%). The highest risks of occupational asthma were found in bakers and pastry makers (683/million), car painters (326/million), hairdressers (308/million), and Wood workers (218/million). Conclusion: Despite likely underreporting, the number of cases of occupational asthma reported to the ONAP was approximately twice the number of compensated cases over the same period. The relevance of the programme is confirmed by the reproducibility of the results year after year, and its consistency with other surveillance programmes. The ONAP programme is useful for the identification of targets for primary prevention.. work-related asthma| respiratory-diseases| united-kingdom| surveillance system| population| risk| exposures| finland| canada.	FEB-2003	work-related asthma| respiratory-diseases| united-kingdom| surveillance system| population| risk| exposures| finland| canada	Ameille, J; Pauli, G; Calastreng-Crinquand, A; Vervloet, D; Iwatsubo, Y; Popin, E; Bayeux-Dunglas, MC; Kopferschmitt-Kubler, MC; Arnaud, G; Bergeret, A; Blaumeiser, M; de Blay, F; Boitel, L; Bonnin, C; Brochard, P; Brun, J; Cabal, C; Cador, B; Caillaud, D; Cantineau, A; Chazenfus, J; Choudat, D; Conso, F; Costes, S; Couot, M; Curtes, JP; Dalphin, JC; Danaud, D; Danjou, P; Delemott, B; Deschamps, F; Dewitte, JD; Didier, A; Dhivert-Donnadieu, H; Doutrellot-Philippon, C; Dufresne-Benetti, F; Dumont, D; Dupas, D; Faucon, D; Fumery, JL; Gabrillargues, D; Garnier, R; Godard, P; Grudzien, F; Hemery, JM; Javelaud, B; Lasfargues, G; Leleu, B; Letourneux, M; Libert, B; Loriot, J; Martin, F; Michel, MP; Nisse, C; Paris, C; Pairon, JC; Penneau-Fontbonne, D; Perdrix, A; Petiet, G; de Santi, PP; Robin, H; Saadjian, M; Smolik, HJ; Soulat, JM; Tarin, C; Terracol, D; Tessier-Cotte, C; de Lara, JMT	Reported incidence of occupational asthma in France, 1996-99: the ONAP programme		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		WORK-RELATED ASTHMA; RESPIRATORY-DISEASES; UNITED-KINGDOM; SURVEILLANCE SYSTEM; POPULATION; RISK; EXPOSURES; FINLAND; CANADA	Aims: To estimate the general and specific incidence of occupational asthma in France in 1996-99; and to describe the distribution of cases by age, sex, suspected causal agents, and occupation. Methods: New cases of occupational asthma were collected by a national surveillance programme, based on voluntary reporting, named Observatoire National des Asthmes Professionnels (ONAP), involving a network of occupational and chest physicians. For each case, the reporting form included information on age, sex, location of workplace, occupation, suspected causal agent, and methods of diagnosis. Estimates of the working population, used to calculate incidence rates by age, sex, region, and occupation, were obtained from the Institut National de la Statistique et des Etudes Economiques (INSEE) and from the French Securite Sociale statistics. Results: In 1996-99, 2178 cases of occupational asthma were reported to the ONAP, giving a mean annual rate of 24/million. Rates in men were higher than rates in women (27/million versus 19/million). The highest rate was observed in the 15-29 years age group (30/million). The most frequently incriminated agents were flour (20.3%), isocyanates (14.1%), latex (7.2%), aldehyde (5.9%), persulphate salts (5.8%), and wood dusts (3.7%). The highest risks of occupational asthma were found in bakers and pastry makers (683/million), car painters (326/million), hairdressers (308/million), and Wood workers (218/million). Conclusion: Despite likely underreporting, the number of cases of occupational asthma reported to the ONAP was approximately twice the number of compensated cases over the same period. The relevance of the programme is confirmed by the reproducibility of the results year after year, and its consistency with other surveillance programmes. The ONAP programme is useful for the identification of targets for primary prevention.	34	129	2003	6	10.1136/oem.60.2.136	Public, Environmental & Occupational Health
Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation. Lower respiratory tract inflammation can be detected by measuring exhaled nitric oxide (NO) concentration at a single exhalation flow rate, but this does not differentiate between alveolar and bronchial NO production. We assessed alveolar NO concentration and bronchial NO flux with an extended method of measuring exhaled NO at several exhalation flow rates in 40 patients with asthma, 17 patients with alveolitis, and 57 healthy control subjects. Bronchial NO flux was higher in asthma (2.5 +/- 0.3 nl/s, p < 0.001) than in alveolitis (0.7 +/- 0.1 nl/s) and healthy control subjects (0.7 + 0.1 nl/s). Alveolar NO concentration was higher in alveolitis (4.1 +/- 0.3 ppb, p < 0.001) than in asthma (1.1 +/- 0.2 ppb) and healthy control subjects (1.1 +/- 0.1 ppb). In asthma, bronchial NO flux correlated with serum level of eosinophil protein X (EPX) (r = 0.60, p < 0.001) and bronchial hyperresponsiveness (r = 0.55, p < 0.001). In alveolitis, alveolar NO concentration correlated inversely with pulmonary diffusing capacity (r = -0.55, p = 0.022) and pulmonary restriction. Glucocorticoid treatment or allergen avoidance normalized bronchial NO flux in asthma and decreased alveolar NO concentration toward normal in alveolitis. In conclusion, extended exhaled NO measurement can be used to separately assess alveolar and bronchial inflammation and to assess disease activity/severity in asthma and alveolitis.. potent oxidant peroxynitrite| nitric-oxide| asthmatic-patients| pulmonary-function| lower airways| methacholine| induction| fibrosis| synthase| air.	JUN-2001	potent oxidant peroxynitrite| nitric-oxide| asthmatic-patients| pulmonary-function| lower airways| methacholine| induction| fibrosis| synthase| air	Lehtimaki, L; Kankaanranta, H; Saarelainen, S; Hahtola, P; Jarvenpaa, R; Koivula, T; Turjanmaa, V; Moilanen, E	Extended exhaled NO measurement differentiates between alveolar and bronchial inflammation		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		POTENT OXIDANT PEROXYNITRITE; NITRIC-OXIDE; ASTHMATIC-PATIENTS; PULMONARY-FUNCTION; LOWER AIRWAYS; METHACHOLINE; INDUCTION; FIBROSIS; SYNTHASE; AIR	Lower respiratory tract inflammation can be detected by measuring exhaled nitric oxide (NO) concentration at a single exhalation flow rate, but this does not differentiate between alveolar and bronchial NO production. We assessed alveolar NO concentration and bronchial NO flux with an extended method of measuring exhaled NO at several exhalation flow rates in 40 patients with asthma, 17 patients with alveolitis, and 57 healthy control subjects. Bronchial NO flux was higher in asthma (2.5 +/- 0.3 nl/s, p < 0.001) than in alveolitis (0.7 +/- 0.1 nl/s) and healthy control subjects (0.7 + 0.1 nl/s). Alveolar NO concentration was higher in alveolitis (4.1 +/- 0.3 ppb, p < 0.001) than in asthma (1.1 +/- 0.2 ppb) and healthy control subjects (1.1 +/- 0.1 ppb). In asthma, bronchial NO flux correlated with serum level of eosinophil protein X (EPX) (r = 0.60, p < 0.001) and bronchial hyperresponsiveness (r = 0.55, p < 0.001). In alveolitis, alveolar NO concentration correlated inversely with pulmonary diffusing capacity (r = -0.55, p = 0.022) and pulmonary restriction. Glucocorticoid treatment or allergen avoidance normalized bronchial NO flux in asthma and decreased alveolar NO concentration toward normal in alveolitis. In conclusion, extended exhaled NO measurement can be used to separately assess alveolar and bronchial inflammation and to assess disease activity/severity in asthma and alveolitis.	29	129	2001	5		General & Internal Medicine; Respiratory System
The relation between fungal propagules in indoor air and home characteristics. Background: Questionnaires are commonly used in epidemiologic studies to obtain information about house characteristics in order to predict the household aeroallergen exposure levels. However, the reliability of the predictions made with the questionnaires has not been evaluated. To address this issue, we compared objectively measured fungal propagules including the most frequently isolated mold genera (i.e., Alternaria, Aspergillus, Cladosporium, Penicillium, etc.) in a large sample of homes and compared these measured values to the questionnaire-determined household characteristics. Methods: As part of a prospective cohort study on the relation between residential allergen exposure and development of asthma in neonates, fungal air samples were collected from infant bedrooms and main living areas in 1000 homes in the Northeast USA, from December 1996 to January 1999. A Burkard portable air sampler was used in combination with DG-18 and MEA agars. A questionnaire was used to obtain information on host and house characteristics that may have an impact on the presence of fungal propagules in the air. This included information on observation of moisture problems (e.g., water leakage or damage, and mold or mildew growth), ventilation and heating facilities, building age and type, number of occupants, annual household income, presence of pets and pests, cleaning regimens, etc. Results: The number of CFU/m(3) air collected on MEA was significantly higher than on DG-18 (means, respectively, 1033.5 and 846.0 CFU/m(3)) (P < 0.0005). However, there was no significant difference between the numbers of CFU/m(3) air collected from the main living area and from the infant bedroom. There was only a very weak relationship between the house characteristics, as described by questionnaire, and the presence of fungal propagules in indoor air. Only the temperature, relative humidity, season, and cats inside homes had a statistically significant impact on the presence of fungal propagules in indoor air. Conclusions: The presence of fungal propagules in indoor air cannot be reliably predicted by home characteristics. Actual measurements are required for fungal exposure assessment, and the use of only;one medium to collect samples in one location in a home might be adequate to represent residential levels of fungi in indoor air.. fungal propagules| house characteristics| indoor air| seasonal variation|molds| prevalence| dampness| dust.	MAY-2001	fungal propagules| house characteristics| indoor air| seasonal variation|molds| prevalence| dampness| dust	Ren, P; Jankun, TM; Belanger, K; Bracken, MB; Leaderer, BP	The relation between fungal propagules in indoor air and home characteristics		ALLERGY	fungal propagules; house characteristics; indoor air; seasonal variation	MOLDS; PREVALENCE; DAMPNESS; DUST	Background: Questionnaires are commonly used in epidemiologic studies to obtain information about house characteristics in order to predict the household aeroallergen exposure levels. However, the reliability of the predictions made with the questionnaires has not been evaluated. To address this issue, we compared objectively measured fungal propagules including the most frequently isolated mold genera (i.e., Alternaria, Aspergillus, Cladosporium, Penicillium, etc.) in a large sample of homes and compared these measured values to the questionnaire-determined household characteristics. Methods: As part of a prospective cohort study on the relation between residential allergen exposure and development of asthma in neonates, fungal air samples were collected from infant bedrooms and main living areas in 1000 homes in the Northeast USA, from December 1996 to January 1999. A Burkard portable air sampler was used in combination with DG-18 and MEA agars. A questionnaire was used to obtain information on host and house characteristics that may have an impact on the presence of fungal propagules in the air. This included information on observation of moisture problems (e.g., water leakage or damage, and mold or mildew growth), ventilation and heating facilities, building age and type, number of occupants, annual household income, presence of pets and pests, cleaning regimens, etc. Results: The number of CFU/m(3) air collected on MEA was significantly higher than on DG-18 (means, respectively, 1033.5 and 846.0 CFU/m(3)) (P < 0.0005). However, there was no significant difference between the numbers of CFU/m(3) air collected from the main living area and from the infant bedroom. There was only a very weak relationship between the house characteristics, as described by questionnaire, and the presence of fungal propagules in indoor air. Only the temperature, relative humidity, season, and cats inside homes had a statistically significant impact on the presence of fungal propagules in indoor air. Conclusions: The presence of fungal propagules in indoor air cannot be reliably predicted by home characteristics. Actual measurements are required for fungal exposure assessment, and the use of only;one medium to collect samples in one location in a home might be adequate to represent residential levels of fungi in indoor air.	14	129	2001	6	10.1034/j.1398-9995.2001.056005419.x	Allergy; Immunology
Expression of chemokine receptors by lung T cells from normal and asthmatic subjects. The lung is an important tertiary lymphoid organ with constant trafficking of T cells through the lung in both health and disease. T cell migration is controlled by a combination of adhesion receptors and chemokines expressed on vascular endothelium and in the tissue, often in an organ-specific manner. This leads to selective accumulation of different T cell subsets, a process called lymphocyte homing. There is evidence for a distinct lung-homing pathway, but no specific lung-homing receptors have been described. We analyzed the chemokine receptor profile of lung T cells to determine the extent to which lung T cells shared homing pathways with other organs such as the gut and skin. In addition, we compared expression of receptors in normal and asthmatic individuals to determine whether different pathways were used in health and disease, We observed that lung T cells expressed a profile of chemokine and adhesion receptors distinct from that of gut- and skin-homing T cells although no chemokine receptor specific for the lung was found. In particular, lung T cells expressed CCR5 and CXCR3, but not CeR9 or cutaneous lymphocyte Ag, and only low levels of CCR4 and alpha (4)beta (7). No differences were observed between lung T cells from normal vs asthmatic subjects. This study provides added support far the concept of a lung-homing pathway separate from other mucosal organs such as the gut and suggests that the chemokine pathways that control T cell migration in normal homeostasis and Th2-type inflammatory responses are similar.. chemoattractant receptors| differential expression| atopic asthma| lymphocytes| recognition| pulmonary| biology.	FEB 15-2001	chemoattractant receptors| differential expression| atopic asthma| lymphocytes| recognition| pulmonary| biology	Campbell, JJ; Brightling, CE; Symon, FA; Qin, S; Murphy, KE; Hodge, M; Andrew, DP; Wu, LJ; Butcher, EC; Wardlaw, AJ	Expression of chemokine receptors by lung T cells from normal and asthmatic subjects		JOURNAL OF IMMUNOLOGY		CHEMOATTRACTANT RECEPTORS; DIFFERENTIAL EXPRESSION; ATOPIC ASTHMA; LYMPHOCYTES; RECOGNITION; PULMONARY; BIOLOGY	The lung is an important tertiary lymphoid organ with constant trafficking of T cells through the lung in both health and disease. T cell migration is controlled by a combination of adhesion receptors and chemokines expressed on vascular endothelium and in the tissue, often in an organ-specific manner. This leads to selective accumulation of different T cell subsets, a process called lymphocyte homing. There is evidence for a distinct lung-homing pathway, but no specific lung-homing receptors have been described. We analyzed the chemokine receptor profile of lung T cells to determine the extent to which lung T cells shared homing pathways with other organs such as the gut and skin. In addition, we compared expression of receptors in normal and asthmatic individuals to determine whether different pathways were used in health and disease, We observed that lung T cells expressed a profile of chemokine and adhesion receptors distinct from that of gut- and skin-homing T cells although no chemokine receptor specific for the lung was found. In particular, lung T cells expressed CCR5 and CXCR3, but not CeR9 or cutaneous lymphocyte Ag, and only low levels of CCR4 and alpha (4)beta (7). No differences were observed between lung T cells from normal vs asthmatic subjects. This study provides added support far the concept of a lung-homing pathway separate from other mucosal organs such as the gut and suggests that the chemokine pathways that control T cell migration in normal homeostasis and Th2-type inflammatory responses are similar.	30	129	2001	7		Immunology
The immune system as a potential target for environmental estrogens (endocrine disrupters): a new emerging field. It is now well known that natural (17 beta-estradiol) and synthetic (e.g. diethylstilbestrol) estrogens not only affect the reproductive system, but also markedly influence the immune system. Recently, a new class of estrogens that is abundant in the environment (in industrial chemicals, pesticides, and surfactants) has been recognized. Some of these estrogenic chemicals (which are a large subgroup of endocrine disrupters) have also been shown to influence the immune system. This review assimilates growing evidence in wildlife, laboratory animals and to a limited extent in humans, which suggests that environmental chemicals may also affect the immune system. Further studies are needed to ascertain the immunological consequences of exposure to environmental estrogens, especially in humans. At the present time, it is not known whether the human immune system responds to a low dose of environmental estrogens or if environmental estrogens influence certain subsets of human populations, rather than the general population. Conceivably, an alteration of the immune system by environmental estrogens could affect the individuals' ability to mount well-regulated immune responses to microbial and vaccine antigens, allergens, self and tumor antigens. Possible changes in the immune system must be investigated routinely in toxicity studies. A comprehensive mechanistic understanding of potential immunomodulatory chemicals is needed. In this regard, relevant laboratory animals may be especially useful in identifying susceptible periods of life, whether both genders are equally affected, in analysis of changes in target lymphoid organs, and to determine the immunological effects of mixtures of chemicals. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.. immune| autoimmune| estrogens| environmental estrogens| endocrine disrupters| allergies|adult male-rats| lupus-erythematosus| sex-hormones| autoimmune-diseases| polychlorinated-biphenyls| organochlorine compounds| autoantibody production| cytokine production| murine splenocytes| gonadal-steroids.	SEP 7-2000	immune| autoimmune| estrogens| environmental estrogens| endocrine disrupters| allergies|adult male-rats| lupus-erythematosus| sex-hormones| autoimmune-diseases| polychlorinated-biphenyls| organochlorine compounds| autoantibody production| cytokine production| murine splenocytes| gonadal-steroids	Ahmed, SR	The immune system as a potential target for environmental estrogens (endocrine disrupters): a new emerging field		TOXICOLOGY	immune; autoimmune; estrogens; environmental estrogens; endocrine disrupters; allergies	ADULT MALE-RATS; LUPUS-ERYTHEMATOSUS; SEX-HORMONES; AUTOIMMUNE-DISEASES; POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE COMPOUNDS; AUTOANTIBODY PRODUCTION; CYTOKINE PRODUCTION; MURINE SPLENOCYTES; GONADAL-STEROIDS	It is now well known that natural (17 beta-estradiol) and synthetic (e.g. diethylstilbestrol) estrogens not only affect the reproductive system, but also markedly influence the immune system. Recently, a new class of estrogens that is abundant in the environment (in industrial chemicals, pesticides, and surfactants) has been recognized. Some of these estrogenic chemicals (which are a large subgroup of endocrine disrupters) have also been shown to influence the immune system. This review assimilates growing evidence in wildlife, laboratory animals and to a limited extent in humans, which suggests that environmental chemicals may also affect the immune system. Further studies are needed to ascertain the immunological consequences of exposure to environmental estrogens, especially in humans. At the present time, it is not known whether the human immune system responds to a low dose of environmental estrogens or if environmental estrogens influence certain subsets of human populations, rather than the general population. Conceivably, an alteration of the immune system by environmental estrogens could affect the individuals' ability to mount well-regulated immune responses to microbial and vaccine antigens, allergens, self and tumor antigens. Possible changes in the immune system must be investigated routinely in toxicity studies. A comprehensive mechanistic understanding of potential immunomodulatory chemicals is needed. In this regard, relevant laboratory animals may be especially useful in identifying susceptible periods of life, whether both genders are equally affected, in analysis of changes in target lymphoid organs, and to determine the immunological effects of mixtures of chemicals. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.	116	129	2000	16		Pharmacology & Pharmacy; Toxicology
The integration of T cell migration, differentiation and function. T cells function locally. Accordingly, T cells' recognition of antigen, their subsequent activation and differentiation, and their role in the processes of infection control, tumour eradication, autoimmunity, allergy and alloreactivity are intrinsically coupled with migration. Recent discoveries revise our understanding of the regulation and patterns of T cell trafficking and reveal limitations in current paradigms. Here, we review classic and emerging concepts, highlight the challenge of integrating new observations with existing T cell classification schemes and summarize the heuristic framework provided by viewing T cell differentiation and function first through the prism of migration.. chemokine receptor ccr7| cd103(+) dendritic cells| lymph-nodes| cutting edge| in-vivo| resident memory| antigen presentation| peripheral-tissues| homing receptor| l-selectin.	MAY-2013	chemokine receptor ccr7| cd103(+) dendritic cells| lymph-nodes| cutting edge| in-vivo| resident memory| antigen presentation| peripheral-tissues| homing receptor| l-selectin	Masopust, D; Schenkel, JM	The integration of T cell migration, differentiation and function		NATURE REVIEWS IMMUNOLOGY		CHEMOKINE RECEPTOR CCR7; CD103(+) DENDRITIC CELLS; LYMPH-NODES; CUTTING EDGE; IN-VIVO; RESIDENT MEMORY; ANTIGEN PRESENTATION; PERIPHERAL-TISSUES; HOMING RECEPTOR; L-SELECTIN	T cells function locally. Accordingly, T cells' recognition of antigen, their subsequent activation and differentiation, and their role in the processes of infection control, tumour eradication, autoimmunity, allergy and alloreactivity are intrinsically coupled with migration. Recent discoveries revise our understanding of the regulation and patterns of T cell trafficking and reveal limitations in current paradigms. Here, we review classic and emerging concepts, highlight the challenge of integrating new observations with existing T cell classification schemes and summarize the heuristic framework provided by viewing T cell differentiation and function first through the prism of migration.	129	128	2013	12	10.1038/nri3442	Immunology
Single-Walled and Multi-Walled Carbon Nanotubes Promote Allergic Immune Responses in Mice. The adjuvant effect of particles on allergic immune responses has been shown to increase with decreasing particle size and increasing particle surface area. Like ultrafine particles, carbon nanotubes (CNTs) have nano-sized dimensions and a large relative surface area and might thus increase allergic responses. Therefore, we examined whether single-walled (sw) and multi-walled (mw) CNTs have the capacity to promote allergic responses in mice, first in an sc injection model and thereafter in an intranasal model. Balb/cA mice were exposed to three doses of swCNT, mwCNT, as well as ultrafine carbon black particles (ufCBPs, Printex90) during sensitization with the allergen ovalbumin (OVA). Five days after an OVA booster, OVA-specific IgE, IgG1, and IgG2a antibodies in serum and the numbers of inflammatory cells and cytokine levels in bronchoalveolar lavage fluid (BALF) were determined. Furthermore, ex vivo OVA-induced cytokine release from mediastinal lymph node (MLN) cells was measured. In separate experiments, differential cell counts were determined in BALF 24 h after a single intranasal exposure to the particles in the absence of allergen. We demonstrate that both swCNT and mwCNT together with OVA strongly increased serum levels of OVA-specific IgE, the number of eosinophils in BALF, and the secretion of Th2-associated cytokines in the MLN. On the other hand, only mwCNT and ufCBP with OVA increased IgG2a levels, neutrophil cell numbers, and tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels in BALF, as well as the acute influx of neutrophils after exposure to the particles alone. This study demonstrates that CNTs promote allergic responses in mice.. carbon nanotubes| adjuvant effect| airway inflammation| allergy| mice| ige|diesel exhaust particles| airway inflammation| adjuvant activity| ultrafine particles| respiratory health| fine particles| ige production| sensitization| toxicity| antigen.	MAY-2009	carbon nanotubes| adjuvant effect| airway inflammation| allergy| mice| ige|diesel exhaust particles| airway inflammation| adjuvant activity| ultrafine particles| respiratory health| fine particles| ige production| sensitization| toxicity| antigen	Nygaard, UC; Hansen, JS; Samuelsen, M; Alberg, T; Marioara, CD; Lovik, M	Single-Walled and Multi-Walled Carbon Nanotubes Promote Allergic Immune Responses in Mice		TOXICOLOGICAL SCIENCES	carbon nanotubes; adjuvant effect; airway inflammation; allergy; mice; IgE	DIESEL EXHAUST PARTICLES; AIRWAY INFLAMMATION; ADJUVANT ACTIVITY; ULTRAFINE PARTICLES; RESPIRATORY HEALTH; FINE PARTICLES; IGE PRODUCTION; SENSITIZATION; TOXICITY; ANTIGEN	The adjuvant effect of particles on allergic immune responses has been shown to increase with decreasing particle size and increasing particle surface area. Like ultrafine particles, carbon nanotubes (CNTs) have nano-sized dimensions and a large relative surface area and might thus increase allergic responses. Therefore, we examined whether single-walled (sw) and multi-walled (mw) CNTs have the capacity to promote allergic responses in mice, first in an sc injection model and thereafter in an intranasal model. Balb/cA mice were exposed to three doses of swCNT, mwCNT, as well as ultrafine carbon black particles (ufCBPs, Printex90) during sensitization with the allergen ovalbumin (OVA). Five days after an OVA booster, OVA-specific IgE, IgG1, and IgG2a antibodies in serum and the numbers of inflammatory cells and cytokine levels in bronchoalveolar lavage fluid (BALF) were determined. Furthermore, ex vivo OVA-induced cytokine release from mediastinal lymph node (MLN) cells was measured. In separate experiments, differential cell counts were determined in BALF 24 h after a single intranasal exposure to the particles in the absence of allergen. We demonstrate that both swCNT and mwCNT together with OVA strongly increased serum levels of OVA-specific IgE, the number of eosinophils in BALF, and the secretion of Th2-associated cytokines in the MLN. On the other hand, only mwCNT and ufCBP with OVA increased IgG2a levels, neutrophil cell numbers, and tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels in BALF, as well as the acute influx of neutrophils after exposure to the particles alone. This study demonstrates that CNTs promote allergic responses in mice.	41	128	2009	11	10.1093/toxsci/kfp057	Toxicology
Altered early infant gut microbiota in children developing allergy up to 5 years of age. Early colonization with bifidobacteria and lactobacilli is postulated to protect children from allergy, while Clostridium (C.) difficile colonization might be associated with allergic disease. Previous studies of infant gut microbiota in relation to subsequent allergy development have mostly employed culture-dependent techniques, studied genera of bacteria and the follow-up period was limited to 2 years. To relate gut microbiota in early infancy, notably bifidobacteria and lactobacilli at species level, to allergy development during the first 5 years of life and study if environmental factors influence the early infant gut microbiota. Fecal samples were collected at 1 week, 1 month and 2 months after birth from 47 Swedish infants, followed prospectively to 5 years of age. Bacterial DNA was analysed with real-time PCR and related to allergy development, family size as well as endotoxin and Fel d 1 levels in house dust samples. Primers binding to C. difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis were used. Children regarded as allergic manifested allergic symptoms and were skin prick test positive during their first 5 years while non-allergic children were neither. Children who developed allergy were significantly less often colonized with lactobacilli group I (Lactobacillus (L.) rhamnosus, L. casei, L. paracasei), Bifidobacterium adolescentis and C. difficile during their first 2 months. Infants colonized with several Bifidobacterium species had been exposed to higher amounts of endotoxin and grew up in larger families than infants harbouring few species. A more diverse gut microbiota early in life might prevent allergy development and may be related to the previously suggested inverse relationship between allergy, family size and endotoxin exposure. Cite this as: Y. M. Sjogren, M. C. Jenmalm, M. F. Bottcher, B. BjorkstEn and E. Sverremark-Ekstrom, Clinical & Experimental Allergy, 2009 (39) 518-526.. allergy| bifidobacteria| clostridium difficile| endotoxin| fel d 1| gut microbiota| infant| lactobacilli| siblings|placebo-controlled trial| species-specific primers| real-time pcr| swedish infants| atopic eczema| intestinal bifidobacteria| fecal microbiota| endotoxin levels| ribosomal-rna| house-dust.	APR-2009	allergy| bifidobacteria| clostridium difficile| endotoxin| fel d 1| gut microbiota| infant| lactobacilli| siblings|placebo-controlled trial| species-specific primers| real-time pcr| swedish infants| atopic eczema| intestinal bifidobacteria| fecal microbiota| endotoxin levels| ribosomal-rna| house-dust	Sjogren, YM; Jenmalm, MC; Bottcher, MF; Bjorksten, B; Sverremark-Ekstrom, E	Altered early infant gut microbiota in children developing allergy up to 5 years of age		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; bifidobacteria; Clostridium difficile; endotoxin; Fel d 1; gut microbiota; infant; lactobacilli; siblings	PLACEBO-CONTROLLED TRIAL; SPECIES-SPECIFIC PRIMERS; REAL-TIME PCR; SWEDISH INFANTS; ATOPIC ECZEMA; INTESTINAL BIFIDOBACTERIA; FECAL MICROBIOTA; ENDOTOXIN LEVELS; RIBOSOMAL-RNA; HOUSE-DUST	Early colonization with bifidobacteria and lactobacilli is postulated to protect children from allergy, while Clostridium (C.) difficile colonization might be associated with allergic disease. Previous studies of infant gut microbiota in relation to subsequent allergy development have mostly employed culture-dependent techniques, studied genera of bacteria and the follow-up period was limited to 2 years. To relate gut microbiota in early infancy, notably bifidobacteria and lactobacilli at species level, to allergy development during the first 5 years of life and study if environmental factors influence the early infant gut microbiota. Fecal samples were collected at 1 week, 1 month and 2 months after birth from 47 Swedish infants, followed prospectively to 5 years of age. Bacterial DNA was analysed with real-time PCR and related to allergy development, family size as well as endotoxin and Fel d 1 levels in house dust samples. Primers binding to C. difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis were used. Children regarded as allergic manifested allergic symptoms and were skin prick test positive during their first 5 years while non-allergic children were neither. Children who developed allergy were significantly less often colonized with lactobacilli group I (Lactobacillus (L.) rhamnosus, L. casei, L. paracasei), Bifidobacterium adolescentis and C. difficile during their first 2 months. Infants colonized with several Bifidobacterium species had been exposed to higher amounts of endotoxin and grew up in larger families than infants harbouring few species. A more diverse gut microbiota early in life might prevent allergy development and may be related to the previously suggested inverse relationship between allergy, family size and endotoxin exposure. Cite this as: Y. M. Sjogren, M. C. Jenmalm, M. F. Bottcher, B. BjorkstEn and E. Sverremark-Ekstrom, Clinical & Experimental Allergy, 2009 (39) 518-526.	41	128	2009	9	10.1111/j.1365-2222.2008.03156.x	Allergy; Immunology
Daily Telemonitoring of Exhaled Nitric Oxide and Symptoms in the Treatment of Childhood Asthma. Rationale Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FE(NO0.05)), a marker of eosinophilic airway inflammation, can be measured at home. Objectives: We assessed daily FE(NO0.05) telemonitoring in the management of childhood asthma. Methods: Children with atopic asthma (n = 151) were randomly assigned to two groups: FE(NO0.05) Plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FE(NO0.05) and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks. Measurements and Main Results: Telemonitoring was feasible with reliable FE(NO0.05) data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV(1) and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weeks was 0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FE(NO0.05) group. Conclusions: Thirty weeks of daily FENO(0.05) and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FENO(0.05) monitoring compared with daily symptom monitoring only.. airway inflammation| inhaled corticosteroid| symptom-free days| lung function| telemedicine|randomized controlled-trial| children| exacerbations| guide| management.	JAN 15-2009	airway inflammation| inhaled corticosteroid| symptom-free days| lung function| telemedicine|randomized controlled-trial| children| exacerbations| guide| management	de Jongste, JC; Carraro, S; Hop, WC; Baraldi, E	Daily Telemonitoring of Exhaled Nitric Oxide and Symptoms in the Treatment of Childhood Asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	airway inflammation; inhaled corticosteroid; symptom-free days; lung function; telemedicine	RANDOMIZED CONTROLLED-TRIAL; CHILDREN; EXACERBATIONS; GUIDE; MANAGEMENT	Rationale Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FE(NO0.05)), a marker of eosinophilic airway inflammation, can be measured at home. Objectives: We assessed daily FE(NO0.05) telemonitoring in the management of childhood asthma. Methods: Children with atopic asthma (n = 151) were randomly assigned to two groups: FE(NO0.05) Plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FE(NO0.05) and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks. Measurements and Main Results: Telemonitoring was feasible with reliable FE(NO0.05) data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV(1) and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weeks was 0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FE(NO0.05) group. Conclusions: Thirty weeks of daily FENO(0.05) and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FENO(0.05) monitoring compared with daily symptom monitoring only.	20	128	2009	5	10.1164/rccm.200807-1010OC	General & Internal Medicine; Respiratory System
Peripheral TRPV1 receptors as targets for drug development: New molecules and mechanisms. Based on the painful effects of exposure to capsaicin, TRPV1 ( transient receptor potential vanilloid subfamily member 1) localization is most readily associated with peripheral sensory neurons, however, TRPV1 is now known to be expressed, albeit at lower levels, in the spinal cord, brain and a wide-range of non-neuronal cells. The latter includes epithelial cells ( e. g. keratinocytes, urothelium, gastric epithelial cells, enterocytes, and pneumocytes) through vascular endothelium and cells of the immune system ( e. g. T-cells and mast cells) to smooth muscle, fibroblasts and hepatocytes. Despite extensive research, the physiological function of TRPV1 in the brain and in non-neuronal tissues remains elusive. The preliminary results are exciting, but many are unconfirmed and/ or contradictory. As yet, studies with TRPV1 knock-out mice have proven unhelpful in clarifying such biological roles. Now that a range of potent and selective TRPV1 antagonists are available in this rapidly expanding research field, further understanding of the biological roles of TRPV1 throughout the body is within reach. In this article, we will summarize the known roles of peripheral TRPV1 receptors in physiology and disease and review the current perspectives for the therapeutic potential of TRPV1 agonists and antagonists in the treatment of a wide range of conditions such as pain, cancer, migraine, chronic cough, asthma, rectal hypersensitivity, inflammatory bowel disease, obesity, overactive bladder and diabetes. New applications of targeting central TRPV1 receptors are reviewed in the accompanying article by Starowicz et al. ( in this issue).. gene-related peptide| sensory nerve desensitization| human epidermal-keratinocytes| acid-induced colitis| obese zucker rats| vanilloid receptor-1| capsaicin receptor| potential vanilloid-1| epithelial-cells| substance-p.	JAN-2008	gene-related peptide| sensory nerve desensitization| human epidermal-keratinocytes| acid-induced colitis| obese zucker rats| vanilloid receptor-1| capsaicin receptor| potential vanilloid-1| epithelial-cells| substance-p	Gunthorpe, MJ; Szallasi, A	Peripheral TRPV1 receptors as targets for drug development: New molecules and mechanisms		CURRENT PHARMACEUTICAL DESIGN		GENE-RELATED PEPTIDE; SENSORY NERVE DESENSITIZATION; HUMAN EPIDERMAL-KERATINOCYTES; ACID-INDUCED COLITIS; OBESE ZUCKER RATS; VANILLOID RECEPTOR-1; CAPSAICIN RECEPTOR; POTENTIAL VANILLOID-1; EPITHELIAL-CELLS; SUBSTANCE-P	Based on the painful effects of exposure to capsaicin, TRPV1 ( transient receptor potential vanilloid subfamily member 1) localization is most readily associated with peripheral sensory neurons, however, TRPV1 is now known to be expressed, albeit at lower levels, in the spinal cord, brain and a wide-range of non-neuronal cells. The latter includes epithelial cells ( e. g. keratinocytes, urothelium, gastric epithelial cells, enterocytes, and pneumocytes) through vascular endothelium and cells of the immune system ( e. g. T-cells and mast cells) to smooth muscle, fibroblasts and hepatocytes. Despite extensive research, the physiological function of TRPV1 in the brain and in non-neuronal tissues remains elusive. The preliminary results are exciting, but many are unconfirmed and/ or contradictory. As yet, studies with TRPV1 knock-out mice have proven unhelpful in clarifying such biological roles. Now that a range of potent and selective TRPV1 antagonists are available in this rapidly expanding research field, further understanding of the biological roles of TRPV1 throughout the body is within reach. In this article, we will summarize the known roles of peripheral TRPV1 receptors in physiology and disease and review the current perspectives for the therapeutic potential of TRPV1 agonists and antagonists in the treatment of a wide range of conditions such as pain, cancer, migraine, chronic cough, asthma, rectal hypersensitivity, inflammatory bowel disease, obesity, overactive bladder and diabetes. New applications of targeting central TRPV1 receptors are reviewed in the accompanying article by Starowicz et al. ( in this issue).	117	128	2008	10		Pharmacology & Pharmacy
Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis. Background: Allergic Rhinitis and its Impact on Asthma in collaboration with the World Health Organization initiative reclassified allergic rhinitis, like asthma, by duration and severity. The Xyzal in Persistent Rhinitis Trial is the first large, long-term clinical trial studying patients with persistent rhinitis as defined by Allergic Rhinitis and its Impact on Asthma. Objectives: Two primary objectives were defined: comparison of the Rhinoconjunctivitis Quality of Life Questionnaire overall score and Total 5 Symptoms Score (rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) over a period of 4 weeks between levocetirizine 5 mg and placebo. Secondary endpoints included similar evaluations at 1 week and 3, 4.5, and 6 months, summary scores for a general health status questionnaire (Medical Outcomes Survey Short Form 36), a pharmacoeconomic assessment, comorbidities, and a safety evaluation. Methods: The Xyzal in Persistent Rhinitis Trial was a 6-month double-blind, placebo-controlled, multicenter, multinational trial in 551 patients. Adults with persistent rhinitis sensitized to both grass pollen and house dust mite were randomized to receive levocetirizine 5 mg/d or placebo. Results: A total of 421 patients completed the full study. Levocetirizine significantly improved both the Rhinoconjunctivitis Quality of Life Questionnaire overall score and the Total 5 Symptoms Score from week 1 to 6 months (all P values < .001). Medical Outcomes Survey Short Form 36 summary scores were also improved in the levocetirizine group compared with the placebo group. Treatment cessation because of lack of effect, comorbidities, and overall costs of disease, and comorbidities per working patient per month (E160.27 vs E108.18) were lower in the levocetirizine group. Conclusion: Levocetirizine was shown to improve quality of life and symptoms and to decrease the overall costs of the disease over the 6-month treatment period.. aria| persistent allergic rhinitis| health-related quality of life| levocetirizine| long-term therapy| pharmacoeconomics|histamine-induced wheal| health-status| double-blind| cetirizine| asthma| rhinoconjunctivitis| questionnaire| epidemiology| loratadine| volunteers.	OCT-2004	aria| persistent allergic rhinitis| health-related quality of life| levocetirizine| long-term therapy| pharmacoeconomics|histamine-induced wheal| health-status| double-blind| cetirizine| asthma| rhinoconjunctivitis| questionnaire| epidemiology| loratadine| volunteers	Bachert, C; Bousquet, J; Canonica, GW; Durham, SR; Klimek, L; Mullol, J; Van Cauwenberge, PB; Van Hammee, G	Levocetirizine improves quality of life and reduces costs in long-term management of persistent allergic rhinitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	ARIA; persistent allergic rhinitis; health-related quality of life; levocetirizine; long-term therapy; pharmacoeconomics	HISTAMINE-INDUCED WHEAL; HEALTH-STATUS; DOUBLE-BLIND; CETIRIZINE; ASTHMA; RHINOCONJUNCTIVITIS; QUESTIONNAIRE; EPIDEMIOLOGY; LORATADINE; VOLUNTEERS	Background: Allergic Rhinitis and its Impact on Asthma in collaboration with the World Health Organization initiative reclassified allergic rhinitis, like asthma, by duration and severity. The Xyzal in Persistent Rhinitis Trial is the first large, long-term clinical trial studying patients with persistent rhinitis as defined by Allergic Rhinitis and its Impact on Asthma. Objectives: Two primary objectives were defined: comparison of the Rhinoconjunctivitis Quality of Life Questionnaire overall score and Total 5 Symptoms Score (rhinorrhea, sneezing, nasal congestion, and nasal and ocular pruritus) over a period of 4 weeks between levocetirizine 5 mg and placebo. Secondary endpoints included similar evaluations at 1 week and 3, 4.5, and 6 months, summary scores for a general health status questionnaire (Medical Outcomes Survey Short Form 36), a pharmacoeconomic assessment, comorbidities, and a safety evaluation. Methods: The Xyzal in Persistent Rhinitis Trial was a 6-month double-blind, placebo-controlled, multicenter, multinational trial in 551 patients. Adults with persistent rhinitis sensitized to both grass pollen and house dust mite were randomized to receive levocetirizine 5 mg/d or placebo. Results: A total of 421 patients completed the full study. Levocetirizine significantly improved both the Rhinoconjunctivitis Quality of Life Questionnaire overall score and the Total 5 Symptoms Score from week 1 to 6 months (all P values < .001). Medical Outcomes Survey Short Form 36 summary scores were also improved in the levocetirizine group compared with the placebo group. Treatment cessation because of lack of effect, comorbidities, and overall costs of disease, and comorbidities per working patient per month (E160.27 vs E108.18) were lower in the levocetirizine group. Conclusion: Levocetirizine was shown to improve quality of life and symptoms and to decrease the overall costs of the disease over the 6-month treatment period.	29	128	2004	7	10.1016/j.jaci.2004.05.070	Allergy; Immunology
Maternal smoking in pregnancy alters neonatal cytokine responses. Background: Maternal cigarette smoking in pregnancy is an important, common and avoidable exposure that has been linked with elevated cord blood ( CB) immunoglobulin E levels and subsequent asthma and allergic disease in childhood. Despite this, there is still very little information about the immunological effects of maternal smoking on the fetus. Methods: This aim of this study was to compare cord blood mononuclear cell (CBMC) cytokine responses to allergens [ ovalbumin ( OVA) or house dust mite (HDM)] and mitogens [ concanavalin A ( ConA) or phytohemaglutinen (PHA)] in neonates whose mothers smoked throughout pregnancy ( n = 17) with responses of neonates whose mothers never smoked ( n = 40). Cell cultures were stimulated for 24 h and supernatants collected for cytokine detection by enzyme-linked immunosorbent assay [ interleukin (IL)-13, IL-6, interferon (IFN) gamma and IL-10]. Cell pellets were also collected for cytokine mRNA detection (IL-5, IL-9, IFNgamma). Results: Maternal smoking in pregnancy was associated with significantly higher neonatal T helper type 2 (IL-13 protein) responses to both HDM ( P = 0.01) and OVA ( P = 0.035). These effects remained statistically significant after allowing for confounding factors, including the effects of maternal atopy. Similar trends were also seen for IL-9mRNA, IL-5mRNA and IL-6 responses, although these were not statistically significant. Although IFNgamma mRNA responses to PHA ( P = 0.015) and ConA ( P = 0.025) were lower if mothers smoked in pregnancy, there were no differences in neonatal (Th1) IFNgamma protein responses to allergens or mitogens. Conclusions: These findings indicate that maternal cigarette smoking can modify aspects of fetal immune function and highlight the need for further studies in this area.. allergens| cord blood| cytokines| pregnancy| smoking|blood mononuclear-cells| interferon-gamma production| cord-blood| parental smoking| allergic sensitization| serum ige| bronchial responsiveness| subsequent development| respiratory-function| 9-year-old children.	OCT-2003	allergens| cord blood| cytokines| pregnancy| smoking|blood mononuclear-cells| interferon-gamma production| cord-blood| parental smoking| allergic sensitization| serum ige| bronchial responsiveness| subsequent development| respiratory-function| 9-year-old children	Noakes, PS; Holt, PG; Prescott, SL	Maternal smoking in pregnancy alters neonatal cytokine responses		ALLERGY	allergens; cord blood; cytokines; pregnancy; smoking	BLOOD MONONUCLEAR-CELLS; INTERFERON-GAMMA PRODUCTION; CORD-BLOOD; PARENTAL SMOKING; ALLERGIC SENSITIZATION; SERUM IGE; BRONCHIAL RESPONSIVENESS; SUBSEQUENT DEVELOPMENT; RESPIRATORY-FUNCTION; 9-YEAR-OLD CHILDREN	Background: Maternal cigarette smoking in pregnancy is an important, common and avoidable exposure that has been linked with elevated cord blood ( CB) immunoglobulin E levels and subsequent asthma and allergic disease in childhood. Despite this, there is still very little information about the immunological effects of maternal smoking on the fetus. Methods: This aim of this study was to compare cord blood mononuclear cell (CBMC) cytokine responses to allergens [ ovalbumin ( OVA) or house dust mite (HDM)] and mitogens [ concanavalin A ( ConA) or phytohemaglutinen (PHA)] in neonates whose mothers smoked throughout pregnancy ( n = 17) with responses of neonates whose mothers never smoked ( n = 40). Cell cultures were stimulated for 24 h and supernatants collected for cytokine detection by enzyme-linked immunosorbent assay [ interleukin (IL)-13, IL-6, interferon (IFN) gamma and IL-10]. Cell pellets were also collected for cytokine mRNA detection (IL-5, IL-9, IFNgamma). Results: Maternal smoking in pregnancy was associated with significantly higher neonatal T helper type 2 (IL-13 protein) responses to both HDM ( P = 0.01) and OVA ( P = 0.035). These effects remained statistically significant after allowing for confounding factors, including the effects of maternal atopy. Similar trends were also seen for IL-9mRNA, IL-5mRNA and IL-6 responses, although these were not statistically significant. Although IFNgamma mRNA responses to PHA ( P = 0.015) and ConA ( P = 0.025) were lower if mothers smoked in pregnancy, there were no differences in neonatal (Th1) IFNgamma protein responses to allergens or mitogens. Conclusions: These findings indicate that maternal cigarette smoking can modify aspects of fetal immune function and highlight the need for further studies in this area.	44	128	2003	6	10.1034/j.1398-9995.2003.00290.x	Allergy; Immunology
Murine models of asthma. In vivo animal models can offer valuable information on several aspects of asthma pathogenesis and treatment. The mouse is increasingly used in these models, mainly because this species allows for the application in vivo of a broad range of immunological tools, including gene deletion technology. Mice, therefore, seem particularly useful to further elucidate factors influencing the response to inhaled allergens. Examples include: the role of immunoregulatory mechanisms that protect against T-helper cell type 2 cell development; the trafficking of T-cells; and the contribution of the innate immunity. However, as for other animal species, murine models also have limitations. Mice do not spontaneously develop asthma and no model mimics the entire asthma phenotype. Instead, mice should be used to model specific traits of the human disease. The present task force report draws attention to specific aspects of lung structure and function that need to be borne in mind when developing such models and interpreting the results. In particular, efforts should be made to develop models that mimic the lung function changes characteristic of asthma as closely as possible. A large section of this report is therefore devoted to an overview of airway function and its measurement in mice.. airway reactivity| asthma| in vivo models| murine|airway smooth-muscle| cd4(+) t-cells| passive sensitization| ige responses| allergen| mice| responsiveness| exposure| mouse| inflammation.	AUG-2003	airway reactivity| asthma| in vivo models| murine|airway smooth-muscle| cd4(+) t-cells| passive sensitization| ige responses| allergen| mice| responsiveness| exposure| mouse| inflammation	Kips, JC; Anderson, GP; Fredberg, JJ; Herz, U; Inman, MD; Jordana, M; Kemeny, DM; Lotvall, J; Pauwels, RA; Plopper, CG; Schmidt, D; Sterk, PJ; Van Oosterhout, AJM; Vargaftig, BB; Chung, KF	Murine models of asthma		EUROPEAN RESPIRATORY JOURNAL	airway reactivity; asthma; in vivo models; murine	AIRWAY SMOOTH-MUSCLE; CD4(+) T-CELLS; PASSIVE SENSITIZATION; IGE RESPONSES; ALLERGEN; MICE; RESPONSIVENESS; EXPOSURE; MOUSE; INFLAMMATION	In vivo animal models can offer valuable information on several aspects of asthma pathogenesis and treatment. The mouse is increasingly used in these models, mainly because this species allows for the application in vivo of a broad range of immunological tools, including gene deletion technology. Mice, therefore, seem particularly useful to further elucidate factors influencing the response to inhaled allergens. Examples include: the role of immunoregulatory mechanisms that protect against T-helper cell type 2 cell development; the trafficking of T-cells; and the contribution of the innate immunity. However, as for other animal species, murine models also have limitations. Mice do not spontaneously develop asthma and no model mimics the entire asthma phenotype. Instead, mice should be used to model specific traits of the human disease. The present task force report draws attention to specific aspects of lung structure and function that need to be borne in mind when developing such models and interpreting the results. In particular, efforts should be made to develop models that mimic the lung function changes characteristic of asthma as closely as possible. A large section of this report is therefore devoted to an overview of airway function and its measurement in mice.	55	128	2003	9	10.1183/09031936.03.00026403	Respiratory System
Maternal medication use and risks of gastroschisis and small intestinal atresia. Gastroschisis and small intestinal atresia (SIA) are birth defects that are thought to arise from vascular disruption of fetal mesenteric vessels. Previous studies of gastroschisis have suggested that risk is increased for maternal use of vasoactive over-the-counter medications, including specific analgesics and decongestants. This retrospective study evaluated the relation between maternal use of cough/cold/analgesic medications and risks of gastroschisis and SIA. From 1995 to 1999, the mothers of 206 gastroschisis cases, 126 SIA cases, and 798 controls in the United States and Canada were interviewed about medication use and illnesses. Risks of gastroschisis were elevated for use of aspirin (odds ratio = 2.7, 95% confidence interval: 1.2, 5.9), pseudoephedrine (odds ratio = 1.8, 95% confidence interval: 1.0, 3.2), acetaminophen (odds ratio = 1.5, 95% confidence interval: 1.1, 2.2), and pseudoephedrine combined with acetaminophen (odds ratio = 4.2, 95% confidence interval: 1.9, 9.2). Risks of SIA were increased for any use of pseudoephedrine (odds ratio = 2.0, 95% confidence interval: 1.0, 4.0) and for use of pseudoephedrine in combination with acetaminophen (odds ratio = 3.0, 95% confidence interval: 1.1, 8.0). Reported fever, upper respiratory infection, and allergy were not associated with risks of either defect. These findings add more evidence that aspirin use in early pregnancy increases risk of gastroschisis. Although pseudoephedrine has previously been shown to increase gastroschisis risk, findings of this study raise questions about interactions between medications and possible confounding by underlying illness.. gastroschisis| intestinal atresia| medicine| pregnancy|vascular disruption| exposure| defects.	JAN 1-2002	gastroschisis| intestinal atresia| medicine| pregnancy|vascular disruption| exposure| defects	Werler, MM; Sheehan, JE; Mitchell, AA	Maternal medication use and risks of gastroschisis and small intestinal atresia		AMERICAN JOURNAL OF EPIDEMIOLOGY	gastroschisis; intestinal atresia; medicine; pregnancy	VASCULAR DISRUPTION; EXPOSURE; DEFECTS	Gastroschisis and small intestinal atresia (SIA) are birth defects that are thought to arise from vascular disruption of fetal mesenteric vessels. Previous studies of gastroschisis have suggested that risk is increased for maternal use of vasoactive over-the-counter medications, including specific analgesics and decongestants. This retrospective study evaluated the relation between maternal use of cough/cold/analgesic medications and risks of gastroschisis and SIA. From 1995 to 1999, the mothers of 206 gastroschisis cases, 126 SIA cases, and 798 controls in the United States and Canada were interviewed about medication use and illnesses. Risks of gastroschisis were elevated for use of aspirin (odds ratio = 2.7, 95% confidence interval: 1.2, 5.9), pseudoephedrine (odds ratio = 1.8, 95% confidence interval: 1.0, 3.2), acetaminophen (odds ratio = 1.5, 95% confidence interval: 1.1, 2.2), and pseudoephedrine combined with acetaminophen (odds ratio = 4.2, 95% confidence interval: 1.9, 9.2). Risks of SIA were increased for any use of pseudoephedrine (odds ratio = 2.0, 95% confidence interval: 1.0, 4.0) and for use of pseudoephedrine in combination with acetaminophen (odds ratio = 3.0, 95% confidence interval: 1.1, 8.0). Reported fever, upper respiratory infection, and allergy were not associated with risks of either defect. These findings add more evidence that aspirin use in early pregnancy increases risk of gastroschisis. Although pseudoephedrine has previously been shown to increase gastroschisis risk, findings of this study raise questions about interactions between medications and possible confounding by underlying illness.	14	128	2002	6	10.1093/aje/155.1.26	Public, Environmental & Occupational Health
Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long-term results from the German Infant Nutritional Intervention Study (GINI). Background: The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated. Objective: We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow's milk formula (CMF) in a randomized, double-blind trial. Methods: Between 1995 and 1998, 2252 newborns with atopic heredity were randomly assigned at birth to receive one of 4 blinded formulas: partially or extensively hydrolyzed whey formula, extensively hydrolyzed casein formula, or CMF as milk substitute for the first 4 months when breast-feeding was insufficient. The cohort was followed from birth until 6 years of age with yearly questionnaires. Outcomes were physician-diagnosed allergic diseases (atopic dermatitis, food allergy, allergic urticaria, asthma, and hay fever/allergic rhinitis). Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis. Results: In the intent-to-treat analysis the relative risk of a physician's diagnosis of allergic manifestation (AM) compared with CMF was 0.82 (95% CI, 0.70-0.96) for partially hydrolyzed whey formula, 0.90 (95% CI, 0.78-1.04) for extensively hydrolyzed whey formula, and 0.80 (95% CI, 0.69-0.93) for extensively hydrolyzed casein formula. The corresponding figures for atopic eczema were 0.79 (95% CI, 0.64-0.97), 0.92 (95% CI, 0.76-1.11), and 0.71 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis all effects were stronger and significant. No significant effect on other AMs was found. Conclusion: The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.. birth cohort| long-term allergy prevention| hydrolysates| double-blind randomized trial|food-allergen avoidance| dietary prevention| childhood asthma| small children| recommendations| disease| atopy| prophylaxis| committee| exposure.	JUN-2008	birth cohort| long-term allergy prevention| hydrolysates| double-blind randomized trial|food-allergen avoidance| dietary prevention| childhood asthma| small children| recommendations| disease| atopy| prophylaxis| committee| exposure	von Berg, A; Filipiak-Pittroff, B; Kraemer, U; Link, E; Bollrath, C; Brockow, I; Koletzko, S; Armin, G; Heinrich, J; Wichmann, HE; Bauer, CP; Reinhardt, D; Berdel, D	Preventive effect of hydrolyzed infant formulas persists until age 6 years: Long-term results from the German Infant Nutritional Intervention Study (GINI)		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	birth cohort; long-term allergy prevention; hydrolysates; double-blind randomized trial	FOOD-ALLERGEN AVOIDANCE; DIETARY PREVENTION; CHILDHOOD ASTHMA; SMALL CHILDREN; RECOMMENDATIONS; DISEASE; ATOPY; PROPHYLAXIS; COMMITTEE; EXPOSURE	Background: The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated. Objective: We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow's milk formula (CMF) in a randomized, double-blind trial. Methods: Between 1995 and 1998, 2252 newborns with atopic heredity were randomly assigned at birth to receive one of 4 blinded formulas: partially or extensively hydrolyzed whey formula, extensively hydrolyzed casein formula, or CMF as milk substitute for the first 4 months when breast-feeding was insufficient. The cohort was followed from birth until 6 years of age with yearly questionnaires. Outcomes were physician-diagnosed allergic diseases (atopic dermatitis, food allergy, allergic urticaria, asthma, and hay fever/allergic rhinitis). Log-binomial regression modeled with generalized estimation equations was used for the statistical analysis. Results: In the intent-to-treat analysis the relative risk of a physician's diagnosis of allergic manifestation (AM) compared with CMF was 0.82 (95% CI, 0.70-0.96) for partially hydrolyzed whey formula, 0.90 (95% CI, 0.78-1.04) for extensively hydrolyzed whey formula, and 0.80 (95% CI, 0.69-0.93) for extensively hydrolyzed casein formula. The corresponding figures for atopic eczema were 0.79 (95% CI, 0.64-0.97), 0.92 (95% CI, 0.76-1.11), and 0.71 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis all effects were stronger and significant. No significant effect on other AMs was found. Conclusion: The data confirm a long-term allergy-preventive effect of hydrolyzed infant formulas on AM and atopic eczema until 6 years of age.	28	127	2008	6	10.1016/j.jaci.2008.04.021	Allergy; Immunology
Stress and inflammation in exacerbations of asthma. In this mini-review, we outline a model depicting the immunologic mechanisms by which psychological stress can exacerbate clinical symptoms in patients with asthma. This model highlights the importance of both social and physical exposures in the exacerbation of asthma symptoms. The basic premise of the model is that psychological stress operates by altering the magnitude of the airway inflammatory response that irritants, allergens, and infections bring about in persons with asthma. The biological pathways for how stress amplifies the immune response to asthma triggers include the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic-adrenal-medullary (SAM) axis, and the sympathetic (SNS) and parasympathetic (PNS) arms of the autonomic nervous system. Empirical evidence for this model is reviewed, and conclusions and future research directions are discussed. (C) 2007 Elsevier Inc. All rights reserved.. stress| asthma| cytokines| glucocorticoids| autonomic nervous system|psychological stress| childhood asthma| socioeconomic-status| cytokine profiles| common cold| expression| children| atopy| susceptibility| adolescents.	NOV-2007	stress| asthma| cytokines| glucocorticoids| autonomic nervous system|psychological stress| childhood asthma| socioeconomic-status| cytokine profiles| common cold| expression| children| atopy| susceptibility| adolescents	Chen, E; Miller, GE	Stress and inflammation in exacerbations of asthma		BRAIN BEHAVIOR AND IMMUNITY	stress; asthma; cytokines; glucocorticoids; autonomic nervous system	PSYCHOLOGICAL STRESS; CHILDHOOD ASTHMA; SOCIOECONOMIC-STATUS; CYTOKINE PROFILES; COMMON COLD; EXPRESSION; CHILDREN; ATOPY; SUSCEPTIBILITY; ADOLESCENTS	In this mini-review, we outline a model depicting the immunologic mechanisms by which psychological stress can exacerbate clinical symptoms in patients with asthma. This model highlights the importance of both social and physical exposures in the exacerbation of asthma symptoms. The basic premise of the model is that psychological stress operates by altering the magnitude of the airway inflammatory response that irritants, allergens, and infections bring about in persons with asthma. The biological pathways for how stress amplifies the immune response to asthma triggers include the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic-adrenal-medullary (SAM) axis, and the sympathetic (SNS) and parasympathetic (PNS) arms of the autonomic nervous system. Empirical evidence for this model is reviewed, and conclusions and future research directions are discussed. (C) 2007 Elsevier Inc. All rights reserved.	31	127	2007	7	10.1016/j.bbi.2007.03.009	Immunology; Neurosciences & Neurology
Reversal of airway hyperresponsiveness by induction of airway mucosal CD4(+) CD25(+) regulatory T cells. An important feature of atopic asthma is the T cell-driven late phase reaction involving transient bronchoconstriction followed by development of airways hyperresponsiveness (AHR). Using a unique rat asthma model we recently showed that the onset and duration of the aeroallergen-induced airway mucosal T cell activation response in sensitized rats is determined by the kinetics of functional maturation of resident airway mucosal dendritic cells (AMDCs) mediated by cognate interactions with CD4(+) T helper memory cells. The study below extends these investigations to chronic aeroallergen exposure. We demonstrate that prevention of ensuing cycles of T cell activation and resultant AHR during chronic exposure of sensitized rats to allergen aerosols is mediated by CD4(+) CD25(+) Foxp3(+) LAG3(+) CTLA(+) CD45RC(+) T cells which appear in the airway mucosa and regional lymph nodes within 24 h of initiation of exposure, and inhibit subsequent Th-mediated upregulation of AMDC functions. These cells exhibit potent regulatory T (T reg) cell activity in both in vivo and ex vivo assay systems. The maintenance of protective T reg activity is absolutely dependent on continuing allergen stimulation, as interruption of exposure leads to waning of T reg activity and reemergence of sensitivity to aeroallergen exposure manifesting as AMDC/T cell upregulation and resurgence of T helper 2 cytokine expression, airways eosinophilia, and AHR.. dendritic cells| inhaled antigen| respiratory-tract| asthmatic reactions| ige responses| in-vivo| allergen| hyperreactivity| inflammation| suppression.	NOV 27-2006	dendritic cells| inhaled antigen| respiratory-tract| asthmatic reactions| ige responses| in-vivo| allergen| hyperreactivity| inflammation| suppression	Strickland, DH; Stumbles, PA; Zosky, GR; Subrata, LS; Thomas, JA; Turner, DJ; Sly, PD; Holt, PG	Reversal of airway hyperresponsiveness by induction of airway mucosal CD4(+) CD25(+) regulatory T cells		JOURNAL OF EXPERIMENTAL MEDICINE		DENDRITIC CELLS; INHALED ANTIGEN; RESPIRATORY-TRACT; ASTHMATIC REACTIONS; IGE RESPONSES; IN-VIVO; ALLERGEN; HYPERREACTIVITY; INFLAMMATION; SUPPRESSION	An important feature of atopic asthma is the T cell-driven late phase reaction involving transient bronchoconstriction followed by development of airways hyperresponsiveness (AHR). Using a unique rat asthma model we recently showed that the onset and duration of the aeroallergen-induced airway mucosal T cell activation response in sensitized rats is determined by the kinetics of functional maturation of resident airway mucosal dendritic cells (AMDCs) mediated by cognate interactions with CD4(+) T helper memory cells. The study below extends these investigations to chronic aeroallergen exposure. We demonstrate that prevention of ensuing cycles of T cell activation and resultant AHR during chronic exposure of sensitized rats to allergen aerosols is mediated by CD4(+) CD25(+) Foxp3(+) LAG3(+) CTLA(+) CD45RC(+) T cells which appear in the airway mucosa and regional lymph nodes within 24 h of initiation of exposure, and inhibit subsequent Th-mediated upregulation of AMDC functions. These cells exhibit potent regulatory T (T reg) cell activity in both in vivo and ex vivo assay systems. The maintenance of protective T reg activity is absolutely dependent on continuing allergen stimulation, as interruption of exposure leads to waning of T reg activity and reemergence of sensitivity to aeroallergen exposure manifesting as AMDC/T cell upregulation and resurgence of T helper 2 cytokine expression, airways eosinophilia, and AHR.	34	127	2006	12	10.1084/jem.20060155	Immunology; Research & Experimental Medicine
The allergic mouse model of asthma: normal smooth muscle in an abnormal lung?. Mice with allergically inflamed airways are widely used as animal models of asthma, but their relevance for human asthma is not understood. We, therefore, examined the time course of changes in respiratory input impedance during induced bronchoconstriction in BALB/c mice sensitized and challenged with ovalbumin. Our results indicate that bronchoconstriction in mice is accompanied by complete closure of substantial regions of the lung and that closure increases markedly when the lungs are allergically inflamed. With the aid of an anatomically accurate computational model of the mouse lung, we show that the hyperresponsiveness of mice with allergically inflamed airways can be explained entirely by a thickening of the airway mucosa and an increased propensity of the airways to close, without the involvement of any increase in the degree of airway smooth muscle shortening. This has implications for the pathophysiology of asthma and suggests that at least some types of asthma may benefit from therapies aimed at manipulating surface tension at the air-liquid interface in the lungs.. inflammation| lung impedance| resistance| elastance| mucosal thickening|respiratory system mechanics| acute pulmonary response| intravenous histamine| forced-oscillations| airway-closure| ventilation distribution| frequency-dependence| asymptomatic asthma| temporal dynamics| tissue mechanics.	JUN-2004	inflammation| lung impedance| resistance| elastance| mucosal thickening|respiratory system mechanics| acute pulmonary response| intravenous histamine| forced-oscillations| airway-closure| ventilation distribution| frequency-dependence| asymptomatic asthma| temporal dynamics| tissue mechanics	Wagers, S; Lundblad, LKA; Ekman, M; Irvin, CG; Bates, JHT	The allergic mouse model of asthma: normal smooth muscle in an abnormal lung?		JOURNAL OF APPLIED PHYSIOLOGY	inflammation; lung impedance; resistance; elastance; mucosal thickening	RESPIRATORY SYSTEM MECHANICS; ACUTE PULMONARY RESPONSE; INTRAVENOUS HISTAMINE; FORCED-OSCILLATIONS; AIRWAY-CLOSURE; VENTILATION DISTRIBUTION; FREQUENCY-DEPENDENCE; ASYMPTOMATIC ASTHMA; TEMPORAL DYNAMICS; TISSUE MECHANICS	Mice with allergically inflamed airways are widely used as animal models of asthma, but their relevance for human asthma is not understood. We, therefore, examined the time course of changes in respiratory input impedance during induced bronchoconstriction in BALB/c mice sensitized and challenged with ovalbumin. Our results indicate that bronchoconstriction in mice is accompanied by complete closure of substantial regions of the lung and that closure increases markedly when the lungs are allergically inflamed. With the aid of an anatomically accurate computational model of the mouse lung, we show that the hyperresponsiveness of mice with allergically inflamed airways can be explained entirely by a thickening of the airway mucosa and an increased propensity of the airways to close, without the involvement of any increase in the degree of airway smooth muscle shortening. This has implications for the pathophysiology of asthma and suggests that at least some types of asthma may benefit from therapies aimed at manipulating surface tension at the air-liquid interface in the lungs.	52	127	2004	9	10.1152/japplphysiol.00924.2003	Physiology; Sport Sciences
Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates. Background: Polymorphism at the pi class glutathione-S-transferase locus (GSTP1) is associated with allergen-induced asthma and related phenotypes. Objective: We sought to determine whether GSTP1 polymorphism influences susceptibility to asthma induced by toluene diisocyanate (TDI). Methods: The role of GSTP1 was assessed in 131 workers exposed to TDI, 92 with TDI-induced asthma and 39 asymptomatic subjects. The phenotype of the disease was characterized by using detailed clinical history, lung volumes, airway responsiveness to methacholine, and airway responsiveness to TDI. GST genotypes were determined by using PCR-based assays. Results: In patients exposed to TDI for 10 or more years, the frequency of the GSTP1 Val/Val genotype was lower in subjects who had asthma (odds ratio, 0.23; 95% confidence interval, 0.05-1.13; P = .074). Similarly, the frequency of this genotype was significantly lower in subjects with evidence of moderate-to-severe airway hyperresponsiveness to methacholine compared with the frequency in subjects with normal or mild hyperresponsiveness (P = .033). Conclusion: These data suggest that homozygosity for the GSTP1*Val allele confers protection against TDI-induced asthma and airway hyperresponsiveness. This view is supported by the finding that the protective effect increases in proportion to the duration of exposure to TDI.. isocyanates| occupational asthma| airway hyperresponsiveness| genetic markers|toluene diisocyanate tdi| sensitized subjects| oxidative stress| inflammation| association| hyperresponsiveness| identification| localization| polymorphism| responses.	MAY-2002	isocyanates| occupational asthma| airway hyperresponsiveness| genetic markers|toluene diisocyanate tdi| sensitized subjects| oxidative stress| inflammation| association| hyperresponsiveness| identification| localization| polymorphism| responses	Mapp, CE; Fryer, AA; De Marzo, N; Pozzato, V; Padoan, M; Boschetto, P; Strange, RC; Hemmingsen, A; Spiteri, MA	Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	isocyanates; occupational asthma; airway hyperresponsiveness; genetic markers	TOLUENE DIISOCYANATE TDI; SENSITIZED SUBJECTS; OXIDATIVE STRESS; INFLAMMATION; ASSOCIATION; HYPERRESPONSIVENESS; IDENTIFICATION; LOCALIZATION; POLYMORPHISM; RESPONSES	Background: Polymorphism at the pi class glutathione-S-transferase locus (GSTP1) is associated with allergen-induced asthma and related phenotypes. Objective: We sought to determine whether GSTP1 polymorphism influences susceptibility to asthma induced by toluene diisocyanate (TDI). Methods: The role of GSTP1 was assessed in 131 workers exposed to TDI, 92 with TDI-induced asthma and 39 asymptomatic subjects. The phenotype of the disease was characterized by using detailed clinical history, lung volumes, airway responsiveness to methacholine, and airway responsiveness to TDI. GST genotypes were determined by using PCR-based assays. Results: In patients exposed to TDI for 10 or more years, the frequency of the GSTP1 Val/Val genotype was lower in subjects who had asthma (odds ratio, 0.23; 95% confidence interval, 0.05-1.13; P = .074). Similarly, the frequency of this genotype was significantly lower in subjects with evidence of moderate-to-severe airway hyperresponsiveness to methacholine compared with the frequency in subjects with normal or mild hyperresponsiveness (P = .033). Conclusion: These data suggest that homozygosity for the GSTP1*Val allele confers protection against TDI-induced asthma and airway hyperresponsiveness. This view is supported by the finding that the protective effect increases in proportion to the duration of exposure to TDI.	29	127	2002	6	10.1067/mai.2002.123234	Allergy; Immunology
International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and eczema. Background-An ecological analysis was conducted of the relationship between tuberculosis notification rates and the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema in 85 centres from 23 countries in which standardised data are available. These essentially comprised countries in Europe as well as the USA, Canada, Australia, and New Zealand. Methods-Tuberculosis notification rates were obtained from the World Health Organization. Data on the prevalence of symptoms of asthma, rhinitis, and eczema in 235 477 children aged 13-14 years were based on the responses to the written and video questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC). The analysis was adjusted for gross national product (GNP) as an estimate of the level of affluence. Results-Tuberculosis notification rates were significantly inversely associated with the lifetime prevalence of wheeze and asthma and the 12 month period prevalence of wheeze at rest as assessed by the video questionnaire. An increase in the tuberculosis notification rates of 25 per 100 000 was associated with an absolute decrease in the prevalence of wheeze ever of 4.7%. Symptoms of allergic rhinoconjunctivitis in the past 12 months were inversely associated with tuberculosis notification rates, but there were no other significant associations with other ISAAC questions on allergic rhinoconjunctivitis or atopic eczema. Conclusions-These findings are consistent with recent experimental evidence which suggests that exposure to Mycobacterium tuberculosis may reduce the risk of developing asthma.. tuberculosis| atopy| asthma|childhood isaac| immune-response| children| allergies| infection| association| worldwide| atopy| mice.	JUN-2000	tuberculosis| atopy| asthma|childhood isaac| immune-response| children| allergies| infection| association| worldwide| atopy| mice	von Mutius, E; Pearce, N; Beasley, R; Cheng, S; von Ehrenstein, O; Bjorksten, B; Weiland, S	International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and eczema		THORAX	tuberculosis; atopy; asthma	CHILDHOOD ISAAC; IMMUNE-RESPONSE; CHILDREN; ALLERGIES; INFECTION; ASSOCIATION; WORLDWIDE; ATOPY; MICE	Background-An ecological analysis was conducted of the relationship between tuberculosis notification rates and the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema in 85 centres from 23 countries in which standardised data are available. These essentially comprised countries in Europe as well as the USA, Canada, Australia, and New Zealand. Methods-Tuberculosis notification rates were obtained from the World Health Organization. Data on the prevalence of symptoms of asthma, rhinitis, and eczema in 235 477 children aged 13-14 years were based on the responses to the written and video questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC). The analysis was adjusted for gross national product (GNP) as an estimate of the level of affluence. Results-Tuberculosis notification rates were significantly inversely associated with the lifetime prevalence of wheeze and asthma and the 12 month period prevalence of wheeze at rest as assessed by the video questionnaire. An increase in the tuberculosis notification rates of 25 per 100 000 was associated with an absolute decrease in the prevalence of wheeze ever of 4.7%. Symptoms of allergic rhinoconjunctivitis in the past 12 months were inversely associated with tuberculosis notification rates, but there were no other significant associations with other ISAAC questions on allergic rhinoconjunctivitis or atopic eczema. Conclusions-These findings are consistent with recent experimental evidence which suggests that exposure to Mycobacterium tuberculosis may reduce the risk of developing asthma.	31	127	2000	5	10.1136/thorax.55.6.449	Respiratory System
"Diet, Metabolites, and ""Western-Lifestyle"" Inflammatory Diseases. One explanation for the increased incidence of allergies, asthma, and even some autoimmune diseases has been the hygiene hypothesis. However, recent studies also highlight an important role for diet and bacterial metabolites in controlling various immune pathways, including gut and immune homeostasis, regulatory T cell biology, and inflammation. Dietary-related metabolites engage ""metabolite-sensing'' G-protein-coupled receptors, such as GPR43, GPR41, GPR109A, GPR120, and GPR35. These receptors are expressed on immune cells and some gut epithelial cells and generally mediate a direct anti-inflammatory effect. Insufficient intake of ""healthy foodstuffs'' adversely affects the production of bacterial metabolites. These metabolites and those derived directly from food drive beneficial downstream effects on immune pathways. We propose that insufficient exposure to dietary and bacterial metabolites might underlie the development of inflammatory disorders in Western countries. This review highlights what is currently known about diet, metabolites, and their associated immune pathways in relation to the development of inflammatory disease.. chain fatty-acids| regulatory t-cells| protein-coupled receptor| germinated barley foodstuff| gut microbiota| ulcerative-colitis| immune-responses| bowel-disease| deacetylase inhibition| airway inflammation."	JUN 19-2014	chain fatty-acids| regulatory t-cells| protein-coupled receptor| germinated barley foodstuff| gut microbiota| ulcerative-colitis| immune-responses| bowel-disease| deacetylase inhibition| airway inflammation	Thorburn, AN; Macia, L; Mackay, CR	"Diet, Metabolites, and ""Western-Lifestyle"" Inflammatory Diseases"		IMMUNITY		CHAIN FATTY-ACIDS; REGULATORY T-CELLS; PROTEIN-COUPLED RECEPTOR; GERMINATED BARLEY FOODSTUFF; GUT MICROBIOTA; ULCERATIVE-COLITIS; IMMUNE-RESPONSES; BOWEL-DISEASE; DEACETYLASE INHIBITION; AIRWAY INFLAMMATION	"One explanation for the increased incidence of allergies, asthma, and even some autoimmune diseases has been the hygiene hypothesis. However, recent studies also highlight an important role for diet and bacterial metabolites in controlling various immune pathways, including gut and immune homeostasis, regulatory T cell biology, and inflammation. Dietary-related metabolites engage ""metabolite-sensing'' G-protein-coupled receptors, such as GPR43, GPR41, GPR109A, GPR120, and GPR35. These receptors are expressed on immune cells and some gut epithelial cells and generally mediate a direct anti-inflammatory effect. Insufficient intake of ""healthy foodstuffs'' adversely affects the production of bacterial metabolites. These metabolites and those derived directly from food drive beneficial downstream effects on immune pathways. We propose that insufficient exposure to dietary and bacterial metabolites might underlie the development of inflammatory disorders in Western countries. This review highlights what is currently known about diet, metabolites, and their associated immune pathways in relation to the development of inflammatory disease."	97	126	2014	10	10.1016/j.immuni.2014.05.014	Immunology
Environmental exposures and gene regulation in disease etiology. OBJECTIVE: Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. DATA SOURCES: We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. DATA SYNTHESIS: Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Mechanisms include regulation of gene translocation, histone modifications, DNA methylation, DNA repair, transcription, RNA stability, alternative RNA splicing, protein degradation, gene copy number, and transposon activation. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. One of the best-studied areas of gene regulation is epigenetics, especially DNA methylation. Our examples of environmentally induced changes in DNA methylation are presented in the context of early development, when methylation patterns are initially laid down. This approach highlights the potential role for altered DNA methylation in fetal origins of adult disease and inheritance of acquired genetic change. CONCLUSIONS: The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. Second, the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health, and reductions in medical costs, if environmental pollution is decreased.. chemicals| disease risk| dna methylation| drug resistance| endocrine disruption| environment| fetal origins of adult disease| gene expression| gene regulation| susceptibility|diesel exhaust particles| activator messenger-rna| airway epithelial-cells| primordial germ-cells| smooth-muscle-cells| parkinsons-disease| prostate-cancer| alpha-synuclein| 2,3,7,8-tetrachlorodibenzo-p-dioxin tcdd| escherichia-coli.	SEP-2007	chemicals| disease risk| dna methylation| drug resistance| endocrine disruption| environment| fetal origins of adult disease| gene expression| gene regulation| susceptibility|diesel exhaust particles| activator messenger-rna| airway epithelial-cells| primordial germ-cells| smooth-muscle-cells| parkinsons-disease| prostate-cancer| alpha-synuclein| 2,3,7,8-tetrachlorodibenzo-p-dioxin tcdd| escherichia-coli	Edwards, TM; Myers, JP	Environmental exposures and gene regulation in disease etiology		ENVIRONMENTAL HEALTH PERSPECTIVES	chemicals; disease risk; DNA methylation; drug resistance; endocrine disruption; environment; fetal origins of adult disease; gene expression; gene regulation; susceptibility	DIESEL EXHAUST PARTICLES; ACTIVATOR MESSENGER-RNA; AIRWAY EPITHELIAL-CELLS; PRIMORDIAL GERM-CELLS; SMOOTH-MUSCLE-CELLS; PARKINSONS-DISEASE; PROSTATE-CANCER; ALPHA-SYNUCLEIN; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; ESCHERICHIA-COLI	OBJECTIVE: Health or disease is shaped for all individuals by interactions between their genes and environment. Exactly how the environment changes gene expression and how this can lead to disease are being explored in a fruitful new approach to environmental health research, representative studies of which are reviewed here. DATA SOURCES: We searched Web of Science and references of relevant publications to understand the diversity of gene regulatory mechanisms affected by environmental exposures with disease implications. DATA SYNTHESIS: Pharmaceuticals, pesticides, air pollutants, industrial chemicals, heavy metals, hormones, nutrition, and behavior can change gene expression through a broad array of gene regulatory mechanisms. Mechanisms include regulation of gene translocation, histone modifications, DNA methylation, DNA repair, transcription, RNA stability, alternative RNA splicing, protein degradation, gene copy number, and transposon activation. Furthermore, chemically induced changes in gene regulation are associated with serious and complex human diseases, including cancer, diabetes and obesity, infertility, respiratory diseases, allergies, and neurodegenerative disorders such as Parkinson and Alzheimer diseases. One of the best-studied areas of gene regulation is epigenetics, especially DNA methylation. Our examples of environmentally induced changes in DNA methylation are presented in the context of early development, when methylation patterns are initially laid down. This approach highlights the potential role for altered DNA methylation in fetal origins of adult disease and inheritance of acquired genetic change. CONCLUSIONS: The reviewed studies indicate that genetic predisposition for disease is best predicted in the context of environmental exposures. Second, the genetic mechanisms investigated in these studies offer new avenues for risk assessment research. Finally, we are likely to witness dramatic improvements in human health, and reductions in medical costs, if environmental pollution is decreased.	110	126	2007	7	10.1289/ehp.9951	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Not all farming environments protect against the development of asthma and wheeze in children. Background: In recent years, studies have shown a protective effect of being raised in a farm environment on the development of hay fever and atopic sensitization. Inconsistent data on the relation of farming to asthma and wheeze have raised some doubt about a true protective effect. Objective: We sought to study the differential effects of farm-associated exposures on specific asthma-related health outcomes. Methods: The cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study included 8263 school-age children from rural areas in 5 European countries. Information on farm-related exposures and health outcomes was obtained by using questionnaires. In subsamples allergen-specific IgE and RNA expression of CD14 and Toll-like receptor genes were measured, and dust from children's mattresses was evaluated for microbial components. Results: Inverse relations with a diagnosis of asthma were found for pig keeping (odds ratio [OR], 0.57; 95% CI, 0.38-0.86), farm milk consumption (OR, 0.77; 95% CI, 0.60-0.99), frequent stay in animal sheds (OR, 0.71; 95% CI, 0.54-0.95), child's involvement in haying (OR, 0.56; 95% CI, 0.38-0.81), and use of silage (OR, 0.55; 95% CI, 0.31-0.98; for nonatopic asthma) and in Germany for agriculture (OR, 0.34; 95% CI, 0.22-0.53). Protective factors were related with higher expression levels of genes of the innate immunity. Potential risk factors for asthma and wheeze were also identified in the farm milieu. Levels of endotoxin and extracellular polysaccharides were related to the health outcomes independently of the farm exposures. Conclusions: The protective effect of being raised in a farm environment was ascribed to distinct exposures. Clinical implications: The development of atopic sensitization and atopic and nonatopic asthma is most likely determined by different environmental factors, possibly reflecting distinct pathomechanisms.. asthma| wheeze| atopic sensitization| farming| microbial components|school-age-children| allergic diseases| farmers children| hay-fever| atopic sensitization| life-style| house dust| prevalence| exposure| deoxynivalenol.	MAY-2007	asthma| wheeze| atopic sensitization| farming| microbial components|school-age-children| allergic diseases| farmers children| hay-fever| atopic sensitization| life-style| house dust| prevalence| exposure| deoxynivalenol	Ege, MJ; Frei, R; Bieli, C; Schram-Bijkerk, D; Waser, M; Benz, MR; Weiss, G; Nyberg, F; van Hage, M; Pershagen, G; Brunekreef, B; Riedler, J; Lauener, R; Braun-Fahrlander, C; von Mutius, E	Not all farming environments protect against the development of asthma and wheeze in children		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; wheeze; atopic sensitization; farming; microbial components	SCHOOL-AGE-CHILDREN; ALLERGIC DISEASES; FARMERS CHILDREN; HAY-FEVER; ATOPIC SENSITIZATION; LIFE-STYLE; HOUSE DUST; PREVALENCE; EXPOSURE; DEOXYNIVALENOL	Background: In recent years, studies have shown a protective effect of being raised in a farm environment on the development of hay fever and atopic sensitization. Inconsistent data on the relation of farming to asthma and wheeze have raised some doubt about a true protective effect. Objective: We sought to study the differential effects of farm-associated exposures on specific asthma-related health outcomes. Methods: The cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle study included 8263 school-age children from rural areas in 5 European countries. Information on farm-related exposures and health outcomes was obtained by using questionnaires. In subsamples allergen-specific IgE and RNA expression of CD14 and Toll-like receptor genes were measured, and dust from children's mattresses was evaluated for microbial components. Results: Inverse relations with a diagnosis of asthma were found for pig keeping (odds ratio [OR], 0.57; 95% CI, 0.38-0.86), farm milk consumption (OR, 0.77; 95% CI, 0.60-0.99), frequent stay in animal sheds (OR, 0.71; 95% CI, 0.54-0.95), child's involvement in haying (OR, 0.56; 95% CI, 0.38-0.81), and use of silage (OR, 0.55; 95% CI, 0.31-0.98; for nonatopic asthma) and in Germany for agriculture (OR, 0.34; 95% CI, 0.22-0.53). Protective factors were related with higher expression levels of genes of the innate immunity. Potential risk factors for asthma and wheeze were also identified in the farm milieu. Levels of endotoxin and extracellular polysaccharides were related to the health outcomes independently of the farm exposures. Conclusions: The protective effect of being raised in a farm environment was ascribed to distinct exposures. Clinical implications: The development of atopic sensitization and atopic and nonatopic asthma is most likely determined by different environmental factors, possibly reflecting distinct pathomechanisms.	41	126	2007	8	10.1016/j.jaci.2007.01.037	Allergy; Immunology
"Risk-taking and coping strategies of adolescents and young adults with food allergy. Background: Fatal food-allergic reactions are most common among adolescents and young adults. Objective: To gain insight toward devising interventions, we queried risk-taking behaviors and coping strategies of persons age 13 to 21 years with food allergy. Methods: We used an Internet-based anonymous questionnaire devised on the basis of data from focus groups. Results: Participants (174 subjects; 49% male; mean age, 16 years) reported the following: 75% had peanut allergy, 75% had 2 or more food allergies, and 87% had been prescribed self-injectable epinephrine. Regarding risk taking, 61% reported that they ""always"" carry self-injectable epinephrine, but frequencies varied according to activities: traveling (94%), restaurants (81%), friends' homes (67%), school dance (61%), wearing tight clothes (53%), and sports (43%). Fifty-four percent indicated purposefully ingesting a potentially unsafe food. Willingness to eat a food labeled ""may contain"" an allergen was reported by 42%. Twenty-nine participants were designated at high risk because they did not always carry epinephrine and ate foods that ""may contain"" allergens. The high-risk group, compared with the rest of the participants (P < .05), felt less ""concern"" about and ""different"" because of their allergy and had more recent reactions. The high-risk group was not distinguishable (P = not significant) by age, sex, or number or severity of reactions. Participants variably (60%) tell their friends about their allergy, but 68% believe education of their friends would make living with food allergy easier. Conclusions: A significant number of teens with food allergy admit to risk taking that varies by social circumstances and perceived risks. The results imply that education of teenagers and, importantly, those around them during social activities might reduce risk taking and its consequences. Clinical implications: Our survey of adolescents and young adults with food allergy revealed risk-taking behaviors that vary by social circumstances and perceived risks, indicating that education of teenagers and their peers might reduce risk taking and its consequences.. food allergy| adolescent| risk taking|dial telephone survey| tree nut allergy| anaphylactic reactions| prevalence| children| peanut."	JUN-2006	food allergy| adolescent| risk taking|dial telephone survey| tree nut allergy| anaphylactic reactions| prevalence| children| peanut	Sampson, MA; Munoz-Furlong, A; Sicherer, SH	Risk-taking and coping strategies of adolescents and young adults with food allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	food allergy; adolescent; risk taking	DIAL TELEPHONE SURVEY; TREE NUT ALLERGY; ANAPHYLACTIC REACTIONS; PREVALENCE; CHILDREN; PEANUT	"Background: Fatal food-allergic reactions are most common among adolescents and young adults. Objective: To gain insight toward devising interventions, we queried risk-taking behaviors and coping strategies of persons age 13 to 21 years with food allergy. Methods: We used an Internet-based anonymous questionnaire devised on the basis of data from focus groups. Results: Participants (174 subjects; 49% male; mean age, 16 years) reported the following: 75% had peanut allergy, 75% had 2 or more food allergies, and 87% had been prescribed self-injectable epinephrine. Regarding risk taking, 61% reported that they ""always"" carry self-injectable epinephrine, but frequencies varied according to activities: traveling (94%), restaurants (81%), friends' homes (67%), school dance (61%), wearing tight clothes (53%), and sports (43%). Fifty-four percent indicated purposefully ingesting a potentially unsafe food. Willingness to eat a food labeled ""may contain"" an allergen was reported by 42%. Twenty-nine participants were designated at high risk because they did not always carry epinephrine and ate foods that ""may contain"" allergens. The high-risk group, compared with the rest of the participants (P < .05), felt less ""concern"" about and ""different"" because of their allergy and had more recent reactions. The high-risk group was not distinguishable (P = not significant) by age, sex, or number or severity of reactions. Participants variably (60%) tell their friends about their allergy, but 68% believe education of their friends would make living with food allergy easier. Conclusions: A significant number of teens with food allergy admit to risk taking that varies by social circumstances and perceived risks. The results imply that education of teenagers and, importantly, those around them during social activities might reduce risk taking and its consequences. Clinical implications: Our survey of adolescents and young adults with food allergy revealed risk-taking behaviors that vary by social circumstances and perceived risks, indicating that education of teenagers and their peers might reduce risk taking and its consequences."	13	126	2006	6	10.1016/j.jaci.2006.03.009	Allergy; Immunology
The role of microorganisms in atopic dermatitis. Atopic dermatitis (AD) is a common, fluctuating skin disease that is often associated with atopic conditions such as asthma and IgE-mediated food allergy and whose skin lesions are characterized by a Th-2 cell-mediated response to environmental antigens. The increasing prevalence and severity of atopic diseases including AD over the last three decades has been attributed to decreased exposure to microorganisms during early life, which may result in an altered Th-1/Th-2-balance and/or reduced T cell regulation of the immune response. Patients with AD exhibit defects in innate and acquired immune responses resulting in a heightened susceptibility to bacterial, fungal and viral infections, most notably colonization by S. aureus. Toxins produced by S. aureus exacerbate disease activity by both the induction of toxin-specific IgE and the activation of various cell types including Th-2 cells, eosinophils and keratinocytes. Allergens expressed by the yeast Malazessia furfur, a component of normal skin flora, have also been implicated in disease pathogenesis in a subset of AD patients. Microorganisms play an influential role in AD pathogenesis, interacting with disease susceptibility genes to cause initiation and/or exacerbation of disease activity.. staphylococcal-enterotoxin-b| lymphocyte-associated antigen| t-cells| antimicrobial peptides| hygiene hypothesis| pityrosporum-ovale| crohns-disease| bacterial superantigens| malassezia-furfur| stratum-corneum.	APR-2006	staphylococcal-enterotoxin-b| lymphocyte-associated antigen| t-cells| antimicrobial peptides| hygiene hypothesis| pityrosporum-ovale| crohns-disease| bacterial superantigens| malassezia-furfur| stratum-corneum	Baker, BS	The role of microorganisms in atopic dermatitis		CLINICAL AND EXPERIMENTAL IMMUNOLOGY		STAPHYLOCOCCAL-ENTEROTOXIN-B; LYMPHOCYTE-ASSOCIATED ANTIGEN; T-CELLS; ANTIMICROBIAL PEPTIDES; HYGIENE HYPOTHESIS; PITYROSPORUM-OVALE; CROHNS-DISEASE; BACTERIAL SUPERANTIGENS; MALASSEZIA-FURFUR; STRATUM-CORNEUM	Atopic dermatitis (AD) is a common, fluctuating skin disease that is often associated with atopic conditions such as asthma and IgE-mediated food allergy and whose skin lesions are characterized by a Th-2 cell-mediated response to environmental antigens. The increasing prevalence and severity of atopic diseases including AD over the last three decades has been attributed to decreased exposure to microorganisms during early life, which may result in an altered Th-1/Th-2-balance and/or reduced T cell regulation of the immune response. Patients with AD exhibit defects in innate and acquired immune responses resulting in a heightened susceptibility to bacterial, fungal and viral infections, most notably colonization by S. aureus. Toxins produced by S. aureus exacerbate disease activity by both the induction of toxin-specific IgE and the activation of various cell types including Th-2 cells, eosinophils and keratinocytes. Allergens expressed by the yeast Malazessia furfur, a component of normal skin flora, have also been implicated in disease pathogenesis in a subset of AD patients. Microorganisms play an influential role in AD pathogenesis, interacting with disease susceptibility genes to cause initiation and/or exacerbation of disease activity.	85	126	2006	9	10.1111/j.1365-2249.2005.02980.x	Immunology
Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood. Background We recently found that paracetamol (acetaminophen) use in late pregnancy was associated with an increased risk of early wheezing in the offspring. Objective To see whether use of paracetamol in late pregnancy is associated with an increased risk of asthma, wheezing and other atopic outcomes in the child at school age. Methods In the population-based Avon Longitudinal Study of Parents and Children, we measured associations of paracetamol and aspirin use in late pregnancy (20-32 weeks) with asthma, hayfever, eczema (n=8511) and wheezing (8381) in the offspring at 69-81 months, and with atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n=6527) and blood total IgE (n=5148) at 7 years. We used logistic and linear regression to analyse binary outcomes and log-transformed IgE, respectively, controlling for potential confounders. Results Use of paracetamol, but not aspirin, in late pregnancy was positively associated with asthma (odds ratios (ORs), comparing children whose mothers took paracetamol 'sometimes' and 'most days/daily' with those whose mothers never took it, 1.22 (95% confidence interval (CI): 1.06-1.41) and 1.62 (95% CI: 0.86-3.04), respectively; P trend=0.0037), wheezing (ORs 1.20 (95% CI: 1.02-1.40) and 1.86 (95% CI: 0.98-3.55), respectively; P trend=0.011), and total IgE (geometric mean ratios 1.14 (95% CI: 1.03-1.26) and 1.52 (95% CI: 0.98-2.38), respectively; P trend=0.0034), but not hayfever, eczema or skin test positivity. The proportion of asthma attributable to paracetamol use in late pregnancy, assuming a causal relation, was 7%. Conclusion: Paracetamol exposure in late gestation may cause asthma, wheezing and elevated IgE in children of school age.. asthma| birth cohort| fetal| ige| paracetamol (acetaminophen)| pregnancy| prenatal| wheezing|glutathione-s-transferase| normal-children| human-fetal| acetaminophen| pregnancy| rat| mouse| cells| lung| complications.	JAN-2005	asthma| birth cohort| fetal| ige| paracetamol (acetaminophen)| pregnancy| prenatal| wheezing|glutathione-s-transferase| normal-children| human-fetal| acetaminophen| pregnancy| rat| mouse| cells| lung| complications	Shaheen, SO; Newson, RB; Henderson, AJ; Headley, JE; Stratton, FD; Jones, RW; Strachan, DP	Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; birth cohort; fetal; IgE; paracetamol (acetaminophen); pregnancy; prenatal; wheezing	GLUTATHIONE-S-TRANSFERASE; NORMAL-CHILDREN; HUMAN-FETAL; ACETAMINOPHEN; PREGNANCY; RAT; MOUSE; CELLS; LUNG; COMPLICATIONS	Background We recently found that paracetamol (acetaminophen) use in late pregnancy was associated with an increased risk of early wheezing in the offspring. Objective To see whether use of paracetamol in late pregnancy is associated with an increased risk of asthma, wheezing and other atopic outcomes in the child at school age. Methods In the population-based Avon Longitudinal Study of Parents and Children, we measured associations of paracetamol and aspirin use in late pregnancy (20-32 weeks) with asthma, hayfever, eczema (n=8511) and wheezing (8381) in the offspring at 69-81 months, and with atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n=6527) and blood total IgE (n=5148) at 7 years. We used logistic and linear regression to analyse binary outcomes and log-transformed IgE, respectively, controlling for potential confounders. Results Use of paracetamol, but not aspirin, in late pregnancy was positively associated with asthma (odds ratios (ORs), comparing children whose mothers took paracetamol 'sometimes' and 'most days/daily' with those whose mothers never took it, 1.22 (95% confidence interval (CI): 1.06-1.41) and 1.62 (95% CI: 0.86-3.04), respectively; P trend=0.0037), wheezing (ORs 1.20 (95% CI: 1.02-1.40) and 1.86 (95% CI: 0.98-3.55), respectively; P trend=0.011), and total IgE (geometric mean ratios 1.14 (95% CI: 1.03-1.26) and 1.52 (95% CI: 0.98-2.38), respectively; P trend=0.0034), but not hayfever, eczema or skin test positivity. The proportion of asthma attributable to paracetamol use in late pregnancy, assuming a causal relation, was 7%. Conclusion: Paracetamol exposure in late gestation may cause asthma, wheezing and elevated IgE in children of school age.	35	126	2005	8	10.1111/j.1365-2222.2005.02151.x	Allergy; Immunology
Effects of dog ownership and genotype on immune development and atopy in infancy. Background: Exposure to furred pets might confer protection against the development of allergic sensitization through a mechanism that is incompletely understood. Objective: The objective of this study was to determine the effects of pet exposure and genotype on immunologic development and the incidence of atopic markers and diseases in the first year of life. Methods: Pet exposure in the home was compared with cytokine secretion patterns (mitogen-stimulated mononuclear cells at birth and age 1 year) and indicators of atopy (allergen-specific and total IgE, eosinophilia, food allergy, atopic dermatitis) in 285 infants. Interactions with genotype at the CD14 locus were also evaluated in the data analyses. Results: Exposure to dogs was associated with reduced allergen sensitization (19% vs 33%, P =.020) and atopic dermatitis (30% vs 51%, P < .001). The risk for atopic dermatitis was further influenced by genotype at the CD14 locus (P =.006), even after adjusting for exposure to dogs (P =.003). Furthermore, infants with the genotype -159TT were less likely to develop atopic dermatitis if they were exposed to a dog (5% vs 43%, P =.04). Last, dog exposure was associated with increased IL-10 (117 vs 79 pg/mL, P =.002) and IL-13 (280 vs 226 pg/mL, P =.013) responses at age 1 year. Conclusions: Having a dog in infancy is associated with higher IL-10 and IL-13 cytokine secretion profiles and reduced allergic sensitization and atopic dermatitis. These findings suggest that postnatal exposure to dogs can influence immune development in a genotype-specific fashion and thereby attenuate the development of atopy in at-risk children.. interleukin-10| hypersensitivity| dogs| cats| children| interleukin-13| allergy| cytokines| cd14| atopic dermatitis|modified th2 response| allergic sensitization| dendritic cells| early exposure| cat allergen| risk-factors| school-age| early-life| 1st year| asthma.	FEB-2004	interleukin-10| hypersensitivity| dogs| cats| children| interleukin-13| allergy| cytokines| cd14| atopic dermatitis|modified th2 response| allergic sensitization| dendritic cells| early exposure| cat allergen| risk-factors| school-age| early-life| 1st year| asthma	Gern, JE; Reardon, CL; Hoffjan, S; Nicolae, D; Li, ZH; Roberg, KA; Neaville, WA; Carlson-Dakes, K; Adler, K; Hamilton, R; Anderson, E; Gilbertson-White, S; Tisler, C; DaSilva, D; Anklam, K; Mikus, LD; Rosenthal, LA; Ober, C; Gangnon, R; Lemanske, RF	Effects of dog ownership and genotype on immune development and atopy in infancy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Interleukin-10; hypersensitivity; dogs; cats; children; Interleukin-13; allergy; cytokines; CD14; atopic dermatitis	MODIFIED TH2 RESPONSE; ALLERGIC SENSITIZATION; DENDRITIC CELLS; EARLY EXPOSURE; CAT ALLERGEN; RISK-FACTORS; SCHOOL-AGE; EARLY-LIFE; 1ST YEAR; ASTHMA	Background: Exposure to furred pets might confer protection against the development of allergic sensitization through a mechanism that is incompletely understood. Objective: The objective of this study was to determine the effects of pet exposure and genotype on immunologic development and the incidence of atopic markers and diseases in the first year of life. Methods: Pet exposure in the home was compared with cytokine secretion patterns (mitogen-stimulated mononuclear cells at birth and age 1 year) and indicators of atopy (allergen-specific and total IgE, eosinophilia, food allergy, atopic dermatitis) in 285 infants. Interactions with genotype at the CD14 locus were also evaluated in the data analyses. Results: Exposure to dogs was associated with reduced allergen sensitization (19% vs 33%, P =.020) and atopic dermatitis (30% vs 51%, P < .001). The risk for atopic dermatitis was further influenced by genotype at the CD14 locus (P =.006), even after adjusting for exposure to dogs (P =.003). Furthermore, infants with the genotype -159TT were less likely to develop atopic dermatitis if they were exposed to a dog (5% vs 43%, P =.04). Last, dog exposure was associated with increased IL-10 (117 vs 79 pg/mL, P =.002) and IL-13 (280 vs 226 pg/mL, P =.013) responses at age 1 year. Conclusions: Having a dog in infancy is associated with higher IL-10 and IL-13 cytokine secretion profiles and reduced allergic sensitization and atopic dermatitis. These findings suggest that postnatal exposure to dogs can influence immune development in a genotype-specific fashion and thereby attenuate the development of atopy in at-risk children.	37	126	2004	8	10.1016/j.jaci.2003.11.017	Allergy; Immunology
"Outdoor air pollution, climatic changes and allergic bronchial asthma. Both the prevalence and severity of respiratory allergic diseases such as bronchial asthma have increased in recent years. Among the factors implicated in this ""epidemic"" are indoor and outdoor airborne pollutants. Urbanisation with its high levels of vehicle emissions and Westernised lifestyle parallels the increase in respiratory allergy in most industrialised countries, and people who live in urban areas tend to be more affected by the disease than those of rural areas. In atopic subjects, exposure to air pollution increases airway responsiveness to aeroallergens. Pollen is a good model with which to study the interrelationship between air pollution and respiratory allergic diseases. Biological aerosols carrying antigenic proteins, such as pollen grains or plant-derived paucimicronic components, can produce allergic symptoms. By adhering to the surface of these airborne allergenic agents, air pollutants could modify their antigenic properties. Several factors influence this interaction, i.e., type of air pollutant, plant species, nutrient balance, climatic factors, degree of airway sensitisation and hyperresponsiveness of exposed subjects. However, the airway mucosal damage and the impaired mucociliary clearance induced by air pollution may facilitate the penetration and the access of inhaled allergens to the cells of the immune system, and so promote airway sensitisation. As a consequence, an enhanced immunoglobulin E-mediated response to aeroallergens and enhanced airway inflammation favoured by air pollution could account for the increasing prevalence of allergic respiratory diseases in urban areas.. air pollution| bronchial asthma| pollen allergy| respiratory allergy| urban air pollution|thunderstorm-associated asthma| diesel exhaust particles| ppm nitrogen-dioxide| ozone exposure| pulmonary-function| grass-pollen| particulate matter| sulfur-dioxide| respiratory responses| nonasthmatic subjects."	SEP-2002	air pollution| bronchial asthma| pollen allergy| respiratory allergy| urban air pollution|thunderstorm-associated asthma| diesel exhaust particles| ppm nitrogen-dioxide| ozone exposure| pulmonary-function| grass-pollen| particulate matter| sulfur-dioxide| respiratory responses| nonasthmatic subjects	D'Amato, G; Liccardi, G; D'Amato, M; Cazzola, M	Outdoor air pollution, climatic changes and allergic bronchial asthma		EUROPEAN RESPIRATORY JOURNAL	air pollution; bronchial asthma; pollen allergy; respiratory allergy; urban air pollution	THUNDERSTORM-ASSOCIATED ASTHMA; DIESEL EXHAUST PARTICLES; PPM NITROGEN-DIOXIDE; OZONE EXPOSURE; PULMONARY-FUNCTION; GRASS-POLLEN; PARTICULATE MATTER; SULFUR-DIOXIDE; RESPIRATORY RESPONSES; NONASTHMATIC SUBJECTS	"Both the prevalence and severity of respiratory allergic diseases such as bronchial asthma have increased in recent years. Among the factors implicated in this ""epidemic"" are indoor and outdoor airborne pollutants. Urbanisation with its high levels of vehicle emissions and Westernised lifestyle parallels the increase in respiratory allergy in most industrialised countries, and people who live in urban areas tend to be more affected by the disease than those of rural areas. In atopic subjects, exposure to air pollution increases airway responsiveness to aeroallergens. Pollen is a good model with which to study the interrelationship between air pollution and respiratory allergic diseases. Biological aerosols carrying antigenic proteins, such as pollen grains or plant-derived paucimicronic components, can produce allergic symptoms. By adhering to the surface of these airborne allergenic agents, air pollutants could modify their antigenic properties. Several factors influence this interaction, i.e., type of air pollutant, plant species, nutrient balance, climatic factors, degree of airway sensitisation and hyperresponsiveness of exposed subjects. However, the airway mucosal damage and the impaired mucociliary clearance induced by air pollution may facilitate the penetration and the access of inhaled allergens to the cells of the immune system, and so promote airway sensitisation. As a consequence, an enhanced immunoglobulin E-mediated response to aeroallergens and enhanced airway inflammation favoured by air pollution could account for the increasing prevalence of allergic respiratory diseases in urban areas."	162	126	2002	14	10.1183/09031936.02.00401402	Respiratory System
Worsening of asthma in children allergic to cats, after indirect exposure to cat at school. Exposure to cat allergen at school might exacerbate symptoms in asthmatic children with cat allergy. To study this, we identified 410 children, 6-12 yr of age, who were being treated for asthma (inhaled steroids and beta -agonists), were allergic to cats, and had no Eat at home. Peak expiratory flow (PEF), asthma symptoms, medication, fever and/or sore throat, and contact with furred pets were recorded twice daily during the last week of summer holidays and the second and third weeks of school. The number of cat owners in each class was recorded. Ninety-two children with asthma reported no contact with furred pets. Among these, children who attended classes with > 18% (median value) cat owners reported significantly decreased PEF, more days with asthma symptoms, and increased use of medication after school started. Those in classes with less than or equal to 18% cat owners reported no change. Children in classes with many cat owners ran a 9-fold increased risk of exacerbated asthma after school start compared with children in classes with few cat owners, after adjusting for age, sex, and fever and/or sore throat. Thus, asthma symptoms, PEF, and the use of asthma medication in children with cat allergy may be affected by indirect cat exposure at school.. peak expiratory flow| day-care-centers| dog can-f-1| symptoms| sensitization| fel-d-1| dust| mite| hyperresponsiveness| environment.	MAR-2001	peak expiratory flow| day-care-centers| dog can-f-1| symptoms| sensitization| fel-d-1| dust| mite| hyperresponsiveness| environment	Almqvist, C; Wickman, M; Perfetti, L; Berglind, N; Renstrom, A; Hedren, M; Larsson, K; Hedlin, G; Malmberg, P	Worsening of asthma in children allergic to cats, after indirect exposure to cat at school		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		PEAK EXPIRATORY FLOW; DAY-CARE-CENTERS; DOG CAN-F-1; SYMPTOMS; SENSITIZATION; FEL-D-1; DUST; MITE; HYPERRESPONSIVENESS; ENVIRONMENT	Exposure to cat allergen at school might exacerbate symptoms in asthmatic children with cat allergy. To study this, we identified 410 children, 6-12 yr of age, who were being treated for asthma (inhaled steroids and beta -agonists), were allergic to cats, and had no Eat at home. Peak expiratory flow (PEF), asthma symptoms, medication, fever and/or sore throat, and contact with furred pets were recorded twice daily during the last week of summer holidays and the second and third weeks of school. The number of cat owners in each class was recorded. Ninety-two children with asthma reported no contact with furred pets. Among these, children who attended classes with > 18% (median value) cat owners reported significantly decreased PEF, more days with asthma symptoms, and increased use of medication after school started. Those in classes with less than or equal to 18% cat owners reported no change. Children in classes with many cat owners ran a 9-fold increased risk of exacerbated asthma after school start compared with children in classes with few cat owners, after adjusting for age, sex, and fever and/or sore throat. Thus, asthma symptoms, PEF, and the use of asthma medication in children with cat allergy may be affected by indirect cat exposure at school.	29	126	2001	5		General & Internal Medicine; Respiratory System
Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease. Background: Although a doubling in the prevalence of atopic disease, including atopic dermatitis, in the Western world over the last few generations has been paralleled by a marked reduction in infectious diseases, especially tuberculosis, it is unclear whether this increase in atopy is causally related to reduced exposure to mycobacteria. Objectives: The aim of this study was to determine whether administration of mycobacterial antigens to atopic individuals might ameliorate their disease. Methods: Forty-one children aged 5 to 18 years with moderate-to-severe atopic dermatitis were enrolled in a randomized, double-blind, placebo-controlled trial, where they were given either one intradermal injection of killed Mycobacterium vaccae (SRL 172) or buffer solution (placebo). Changes in skin surface area affected by dermatitis and dermatitis severity score were assessed before treatment and at 1 and 3 months after treatment. Results: Children treated with SRL 172 showed a mean 48% (95% CI, 32%-65%) reduction in surface area affected by dermatitis compared with a mean 4% (95% CI, -29% to 22%) reduction for the placebo group (P < .001) and a median 68% (interquartile range, 46%-85%) reduction in dermatitis severity score compared with 18% (interquartile range, -2% to 34%) for the placebo group (P < .01) at 3 months after treatment. There were no untoward effects of the treatment, apart from a local reaction in 13 of the 21 children, which occurred 1 month after SRL 172 administration and settled spontaneously. Conclusion: SRL 172 was associated with an improvement in the severity of the dermatitis in children with moderate-to-severe disease.. mycobacterium vaccae| atopic dermatitis| atopy| t(h)2|allergic disease| bcg vaccination| dendritic cells| infection| immunotherapy| tuberculosis| lymphocytes| ovalbumin| asthma| trial.	MAR-2001	mycobacterium vaccae| atopic dermatitis| atopy| t(h)2|allergic disease| bcg vaccination| dendritic cells| infection| immunotherapy| tuberculosis| lymphocytes| ovalbumin| asthma| trial	Arkwright, PD; David, TJ	Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Mycobacterium vaccae; atopic dermatitis; atopy; T(H)2	ALLERGIC DISEASE; BCG VACCINATION; DENDRITIC CELLS; INFECTION; IMMUNOTHERAPY; TUBERCULOSIS; LYMPHOCYTES; OVALBUMIN; ASTHMA; TRIAL	Background: Although a doubling in the prevalence of atopic disease, including atopic dermatitis, in the Western world over the last few generations has been paralleled by a marked reduction in infectious diseases, especially tuberculosis, it is unclear whether this increase in atopy is causally related to reduced exposure to mycobacteria. Objectives: The aim of this study was to determine whether administration of mycobacterial antigens to atopic individuals might ameliorate their disease. Methods: Forty-one children aged 5 to 18 years with moderate-to-severe atopic dermatitis were enrolled in a randomized, double-blind, placebo-controlled trial, where they were given either one intradermal injection of killed Mycobacterium vaccae (SRL 172) or buffer solution (placebo). Changes in skin surface area affected by dermatitis and dermatitis severity score were assessed before treatment and at 1 and 3 months after treatment. Results: Children treated with SRL 172 showed a mean 48% (95% CI, 32%-65%) reduction in surface area affected by dermatitis compared with a mean 4% (95% CI, -29% to 22%) reduction for the placebo group (P < .001) and a median 68% (interquartile range, 46%-85%) reduction in dermatitis severity score compared with 18% (interquartile range, -2% to 34%) for the placebo group (P < .01) at 3 months after treatment. There were no untoward effects of the treatment, apart from a local reaction in 13 of the 21 children, which occurred 1 month after SRL 172 administration and settled spontaneously. Conclusion: SRL 172 was associated with an improvement in the severity of the dermatitis in children with moderate-to-severe disease.	20	126	2001	4	10.1067/mai.20001.113081	Allergy; Immunology
Indirect bronchial hyperresponsiveness in asthma: mechanisms pharmacology and implications for clinical research. Bronchial hyperresponsiveness (BHR), an abnormal increase in airflow limitation following the exposure to a stimulus, is an important pathophysiological characteristic of bronchial asthma. Because of heterogeneity of the airway response to different stimuli, the latter have been divided into direct and indirect stimuli. Direct stimuli cause airflow limitation by a direct action on the effector cells involved in the airflow limitation, while indirect stimuli exert their action essentially on inflammatory and neuronal cells that act as an intermediary between the stimulus and the effector cells. This manuscript reviews the clinical and experimental studies on the mechanisms involved in indirect BHR in patients with asthma. Pharmacological stimuli (adenosine, tachykinins, bradykinin, sodium metabisulphite/sulphur dioxide, and propranolol) as well as physical stimuli (exercise, nonisotonic aerosols, and isocapnic hyperventilation) are discussed. The results of the different direct and indirect bronchial challenge tests are only weakly correlated and are therefore not mutually interchangeable. Limited available data (studies on the effects of allergen avoidance and inhaled corticosteroids) suggest that indirectly acting bronchial stimuli (especially adenosine) might better reflect the degree of airway inflammation than directly acting stimuli. It remains to be established whether monitoring of indirect BHR as a surrogate marker of inflammation tin addition to symptoms and lung function) is of clinical relevance to the long-term management of asthmatic patients. This seems to be the case for the direct stimulus methacholine. More work needs to be performed to find out whether, indirect stimuli are more suitable in asthma monitoring than direct ones. Recommendations on the application of indirect challenges in clinical practice and research will shortly be available from the European Respiratory Society Task Force.. adenosine challenge| airway inflammation| asthma| bronchial challenges| bronchial hyperresponsiveness| exercise challenge|exercise-induced asthma| nebulized distilled water| metabisulfite-induced bronchoconstriction| bradykinin-induced bronchoconstriction| saline-induced bronchoconstriction| propranolol-induced bronchoconstriction| neutral endopeptidase inhibitor| a-induced bronchoconstriction| methacholine-induced bronchoconstriction| adenosine-induced bronchoconstriction.	SEP-2000	adenosine challenge| airway inflammation| asthma| bronchial challenges| bronchial hyperresponsiveness| exercise challenge|exercise-induced asthma| nebulized distilled water| metabisulfite-induced bronchoconstriction| bradykinin-induced bronchoconstriction| saline-induced bronchoconstriction| propranolol-induced bronchoconstriction| neutral endopeptidase inhibitor| a-induced bronchoconstriction| methacholine-induced bronchoconstriction| adenosine-induced bronchoconstriction	Van Schoor, J; Joos, GF; Pauwels, RA	Indirect bronchial hyperresponsiveness in asthma: mechanisms pharmacology and implications for clinical research		EUROPEAN RESPIRATORY JOURNAL	adenosine challenge; airway inflammation; asthma; bronchial challenges; bronchial hyperresponsiveness; exercise challenge	EXERCISE-INDUCED ASTHMA; NEBULIZED DISTILLED WATER; METABISULFITE-INDUCED BRONCHOCONSTRICTION; BRADYKININ-INDUCED BRONCHOCONSTRICTION; SALINE-INDUCED BRONCHOCONSTRICTION; PROPRANOLOL-INDUCED BRONCHOCONSTRICTION; NEUTRAL ENDOPEPTIDASE INHIBITOR; A-INDUCED BRONCHOCONSTRICTION; METHACHOLINE-INDUCED BRONCHOCONSTRICTION; ADENOSINE-INDUCED BRONCHOCONSTRICTION	Bronchial hyperresponsiveness (BHR), an abnormal increase in airflow limitation following the exposure to a stimulus, is an important pathophysiological characteristic of bronchial asthma. Because of heterogeneity of the airway response to different stimuli, the latter have been divided into direct and indirect stimuli. Direct stimuli cause airflow limitation by a direct action on the effector cells involved in the airflow limitation, while indirect stimuli exert their action essentially on inflammatory and neuronal cells that act as an intermediary between the stimulus and the effector cells. This manuscript reviews the clinical and experimental studies on the mechanisms involved in indirect BHR in patients with asthma. Pharmacological stimuli (adenosine, tachykinins, bradykinin, sodium metabisulphite/sulphur dioxide, and propranolol) as well as physical stimuli (exercise, nonisotonic aerosols, and isocapnic hyperventilation) are discussed. The results of the different direct and indirect bronchial challenge tests are only weakly correlated and are therefore not mutually interchangeable. Limited available data (studies on the effects of allergen avoidance and inhaled corticosteroids) suggest that indirectly acting bronchial stimuli (especially adenosine) might better reflect the degree of airway inflammation than directly acting stimuli. It remains to be established whether monitoring of indirect BHR as a surrogate marker of inflammation tin addition to symptoms and lung function) is of clinical relevance to the long-term management of asthmatic patients. This seems to be the case for the direct stimulus methacholine. More work needs to be performed to find out whether, indirect stimuli are more suitable in asthma monitoring than direct ones. Recommendations on the application of indirect challenges in clinical practice and research will shortly be available from the European Respiratory Society Task Force.	293	126	2000	20	10.1034/j.1399-3003.2000.016003514.x	Respiratory System
Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge. Purpose: The purpose of this study was to compare a laboratory based exercise challenge (LBC) to a field based exercise challenge (FBC) for pulmonary function test (PFT) exercise-induced asthma (EIA) screening of elite athletes. Methods: Twenty-three elite cold weather athletes (14 men, 9 women) PFT positive for EIA (FBC screened) served as subjects. Twenty-three gender and sport matched Controls (nonasthmatics) were randomly selected to establish PFT reference values for normal elite athletes. Before FBC, athletes completed a medical history questionnaire for EIA symptoms. FBC evaluations consisted of baseline spirometry, actual or simulated competition, and 5, 10, and 15 min postexercise spirometry. PFT positive athletes were evaluated in the laboratory using an exercise challenge simulating race intensity (ambient conditions: 21 degrees C, 60% relative humidity). PFT procedures were identical to FBC. Results: 91%, of PFT positive and 48% of PFT normal athletes reported at least one symptom of EIA, with postrace cough most frequent. Baseline spirometry was the same for PFT positives and normal controls. Lower limit reference range (MN - 2 SD) of FEV1 for controls suggests that postexercise decrements of greater than similar to-7% indicate abnormal airway response in this population. Exercise time duration did not effect bronchial reactivity; 78% of FBC PFT positives; were PFT normal post-LBC. Conclusion: Self-reported symptoms by elite athletes are not reliable in identifying EIA. Reference range criterion for FEV1 decrement in the elite athlete postexercise contrasts current recommended guidelines. Moreover, a large number of false negatives may occur in this population if EIA screening is performed with inadequate exercise and environmental stress.. bronchospasm| athlete| exercise| cold| pulmonary function test|cross-country skiers| induced bronchospasm| cold-air| figure skaters| responsiveness| inhalation| hyperpnea| diagnosis| exposure| severity.	FEB-2000	bronchospasm| athlete| exercise| cold| pulmonary function test|cross-country skiers| induced bronchospasm| cold-air| figure skaters| responsiveness| inhalation| hyperpnea| diagnosis| exposure| severity	Rundell, KW; Wilber, RL; Szmedra, L; Jenkinson, DM; Mayers, LB; Im, J	Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge		MEDICINE AND SCIENCE IN SPORTS AND EXERCISE	bronchospasm; athlete; exercise; cold; pulmonary function test	CROSS-COUNTRY SKIERS; INDUCED BRONCHOSPASM; COLD-AIR; FIGURE SKATERS; RESPONSIVENESS; INHALATION; HYPERPNEA; DIAGNOSIS; EXPOSURE; SEVERITY	Purpose: The purpose of this study was to compare a laboratory based exercise challenge (LBC) to a field based exercise challenge (FBC) for pulmonary function test (PFT) exercise-induced asthma (EIA) screening of elite athletes. Methods: Twenty-three elite cold weather athletes (14 men, 9 women) PFT positive for EIA (FBC screened) served as subjects. Twenty-three gender and sport matched Controls (nonasthmatics) were randomly selected to establish PFT reference values for normal elite athletes. Before FBC, athletes completed a medical history questionnaire for EIA symptoms. FBC evaluations consisted of baseline spirometry, actual or simulated competition, and 5, 10, and 15 min postexercise spirometry. PFT positive athletes were evaluated in the laboratory using an exercise challenge simulating race intensity (ambient conditions: 21 degrees C, 60% relative humidity). PFT procedures were identical to FBC. Results: 91%, of PFT positive and 48% of PFT normal athletes reported at least one symptom of EIA, with postrace cough most frequent. Baseline spirometry was the same for PFT positives and normal controls. Lower limit reference range (MN - 2 SD) of FEV1 for controls suggests that postexercise decrements of greater than similar to-7% indicate abnormal airway response in this population. Exercise time duration did not effect bronchial reactivity; 78% of FBC PFT positives; were PFT normal post-LBC. Conclusion: Self-reported symptoms by elite athletes are not reliable in identifying EIA. Reference range criterion for FEV1 decrement in the elite athlete postexercise contrasts current recommended guidelines. Moreover, a large number of false negatives may occur in this population if EIA screening is performed with inadequate exercise and environmental stress.	38	126	2000	8	10.1097/00005768-200002000-00010	Sport Sciences
Measles history and atopic diseases - A population-based cross-sectional study. Context Many recent cross-sectional studies have suggested that lack of early exposure to communicable diseases, including measles, in affluent countries may have increased rates of atopic disease. Objective To study the association between natural measles infection and atopy, Design and Setting Cross-sectional nationwide study in Finland using data gathered between November 1, 1982, and June 30, 1986. Subjects A total of 547 910 individuals aged 14 months to 19 years who at the time of measles-mumps-rubella (MMR) vaccination had relevant information collected on the occurrence of measles and allergic rhinitis, eczema, and asthma. Main Outcome Measures Lifetime occurrence of atopic manifestations in subjects who had had measles compared with those who had not, expressed as age-specific and age-adjusted prevalence ratios. Results The age-adjusted prevalence ratio of atopic manifestations among those who had had measles (n = 20 690) compared with those who had not (n = 527 220) was 1.32 (95% confidence interval [CI], 1.27-1.36) for eczema, 1.41 (95% CI, 1.33-1.49) for rhinitis, and 1.67 (95% CI, 1.54-1.79) for asthma. The positive association between measles and atopy was evident at all ages, in both urban and rural dwellers, and among subjects with many or few contacts at home or in day care. Conclusions Based on our data, measles and atopy occur more frequently together than expected, which does not support the hypothesis that experiencing natural measles infection offers protection against atopic disease.. vaccination program| asthma| infections| childhood| rubella| finland| mumps| children| size.	JAN 19-2000	vaccination program| asthma| infections| childhood| rubella| finland| mumps| children| size	Paunio, M; Heinonen, OP; Virtanen, M; Leinikki, P; Patja, A; Peltola, H	Measles history and atopic diseases - A population-based cross-sectional study		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		VACCINATION PROGRAM; ASTHMA; INFECTIONS; CHILDHOOD; RUBELLA; FINLAND; MUMPS; CHILDREN; SIZE	Context Many recent cross-sectional studies have suggested that lack of early exposure to communicable diseases, including measles, in affluent countries may have increased rates of atopic disease. Objective To study the association between natural measles infection and atopy, Design and Setting Cross-sectional nationwide study in Finland using data gathered between November 1, 1982, and June 30, 1986. Subjects A total of 547 910 individuals aged 14 months to 19 years who at the time of measles-mumps-rubella (MMR) vaccination had relevant information collected on the occurrence of measles and allergic rhinitis, eczema, and asthma. Main Outcome Measures Lifetime occurrence of atopic manifestations in subjects who had had measles compared with those who had not, expressed as age-specific and age-adjusted prevalence ratios. Results The age-adjusted prevalence ratio of atopic manifestations among those who had had measles (n = 20 690) compared with those who had not (n = 527 220) was 1.32 (95% confidence interval [CI], 1.27-1.36) for eczema, 1.41 (95% CI, 1.33-1.49) for rhinitis, and 1.67 (95% CI, 1.54-1.79) for asthma. The positive association between measles and atopy was evident at all ages, in both urban and rural dwellers, and among subjects with many or few contacts at home or in day care. Conclusions Based on our data, measles and atopy occur more frequently together than expected, which does not support the hypothesis that experiencing natural measles infection offers protection against atopic disease.	22	126	2000	4	10.1001/jama.283.3.343	General & Internal Medicine
Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma. Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m(3)) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and Collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-beta 1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-beta 1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-beta 1, which stimulates Collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.. carbon nanotubes| asthma| fibrosis| lung|intratracheal instillation| pulmonary toxicity| mice| particles| interleukin-13| fibroblasts| deposition| responses| exposure.	MAR-2009	carbon nanotubes| asthma| fibrosis| lung|intratracheal instillation| pulmonary toxicity| mice| particles| interleukin-13| fibroblasts| deposition| responses| exposure	Ryman-Rasmussen, JP; Tewksbury, EW; Moss, OR; Cesta, MF; Wong, BA; Bonner, JC	Inhaled Multiwalled Carbon Nanotubes Potentiate Airway Fibrosis in Murine Allergic Asthma		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	carbon nanotubes; asthma; fibrosis; lung	INTRATRACHEAL INSTILLATION; PULMONARY TOXICITY; MICE; PARTICLES; INTERLEUKIN-13; FIBROBLASTS; DEPOSITION; RESPONSES; EXPOSURE	Carbon nanotubes are gaining increasing attention due to possible health risks from occupational or environmental exposures. This study tested the hypothesis that inhaled multiwalled carbon nanotubes (MWCNT) would increase airway fibrosis in mice with allergic asthma. Normal and ovalbumin-sensitized mice were exposed to a MWCNT aerosol (100 mg/m(3)) or saline aerosol for 6 hours. Lung injury, inflammation, and fibrosis were examined by histopathology, clinical chemistry, ELISA, or RT-PCR for cytokines/chemokines, growth factors, and Collagen at 1 and 14 days after inhalation. Inhaled MWCNT were distributed throughout the lung and found in macrophages by light microscopy, but were also evident in epithelial cells by electron microscopy. Quantitative morphometry showed significant airway fibrosis at 14 days in mice that received a combination of ovalbumin and MWCNT, but not in mice that received ovalbumin or MWCNT only. Ovalbumin-sensitized mice that did not inhale MWCNT had elevated levels IL-13 and transforming growth factor (TGF)-beta 1 in lung lavage fluid, but not platelet-derived growth factor (PDGF)-AA. In contrast, unsensitized mice that inhaled MWCNT had elevated PDGF-AA, but not increased levels of TGF-beta 1 and IL-13. This suggested that airway fibrosis resulting from combined ovalbumin sensitization and MWCNT inhalation requires PDGF, a potent fibroblast mitogen, and TGF-beta 1, which stimulates Collagen production. Combined ovalbumin sensitization and MWCNT inhalation also synergistically increased IL-5 mRNA levels, which could further contribute to airway fibrosis. These data indicate that inhaled MWCNT require pre-existing inflammation to cause airway fibrosis. Our findings suggest that individuals with pre-existing allergic inflammation may be susceptible to airway fibrosis from inhaled MWCNT.	33	125	2009	10	10.1165/rcmb.2008-0276OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
A Multivariate Analysis of Risk Factors for the Air-Trapping Asthmatic Phenotype as Measured by Quantitative CT Analysis. Background: Patients with severe asthma have increased physiologically measured air trapping; however, a study using CT measures of air trapping has not been performed. This study was designed to address two hypotheses: (1) air trapping measured by multidetector CT (MDCT) quantitative methodology would be a predictor of a more severe asthma phenotype; and (2) historical, clinical, allergic, or inflammatory risk factors could be identified via multivariate analysis. Methods: MDCT scanning of a subset of Severe Asthma Research Program subjects ,vas performed at functional residual capacity. Air trapping was defined as >= 9.66% of the lung tissue < - 850 Hounsfield units (HU). Subjects classified as having air trapping were then compared to subjects without air trapping on clinical and demographic factors using both univariate and multivariate statistical analyses. Results: Subjects with air trapping were significantly more likely to have a history of asthma-related hospitalizations, ICU visits, and/or mechanical ventilation.. Duration of asthma a (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.08 to 1.87), history pneumonia (OR, 8.55; 95% CI, 2.07 to 35.26), high levels of airway neutrophils (OR, 8.67; 95% CI, 2.05 to 36.57), airflow obstruction (FEN(1)/FVC) OR, 1.61; 95% CI, 1.21 to 2.14], and atopy (OR, 11.54; 95% CI, 1.97 to 67.70) were identified as independent risk factors associated with the air-trapping phenotype. Conclusions: Quantitative CT-determined air trapping in asthmatic subjects identifies a group of individuals it high risk for severe disease. Several independent risk factors for the presence of this phenotype were identified: perhaps most interestingly, history of Pneumonia, neutrophilic inflammation, and atopy. (CHEST 2009; 135:48-56). air trapping| asthma| atopy| neutrophils| quantitative ct|obstructive pulmonary-disease| volume reduction surgery| computed-tomography| objective quantification| lung densitometry| human neutrophils| flow obstruction| allergic-asthma| emphysema| density.	JAN-2009	air trapping| asthma| atopy| neutrophils| quantitative ct|obstructive pulmonary-disease| volume reduction surgery| computed-tomography| objective quantification| lung densitometry| human neutrophils| flow obstruction| allergic-asthma| emphysema| density	Busacker, A; Newell, JD; Keefe, T; Hoffman, EA; Granroth, JC; Castro, M; Fain, S; Wenzel, S	A Multivariate Analysis of Risk Factors for the Air-Trapping Asthmatic Phenotype as Measured by Quantitative CT Analysis		CHEST	air trapping; asthma; atopy; neutrophils; quantitative CT	OBSTRUCTIVE PULMONARY-DISEASE; VOLUME REDUCTION SURGERY; COMPUTED-TOMOGRAPHY; OBJECTIVE QUANTIFICATION; LUNG DENSITOMETRY; HUMAN NEUTROPHILS; FLOW OBSTRUCTION; ALLERGIC-ASTHMA; EMPHYSEMA; DENSITY	Background: Patients with severe asthma have increased physiologically measured air trapping; however, a study using CT measures of air trapping has not been performed. This study was designed to address two hypotheses: (1) air trapping measured by multidetector CT (MDCT) quantitative methodology would be a predictor of a more severe asthma phenotype; and (2) historical, clinical, allergic, or inflammatory risk factors could be identified via multivariate analysis. Methods: MDCT scanning of a subset of Severe Asthma Research Program subjects ,vas performed at functional residual capacity. Air trapping was defined as >= 9.66% of the lung tissue < - 850 Hounsfield units (HU). Subjects classified as having air trapping were then compared to subjects without air trapping on clinical and demographic factors using both univariate and multivariate statistical analyses. Results: Subjects with air trapping were significantly more likely to have a history of asthma-related hospitalizations, ICU visits, and/or mechanical ventilation.. Duration of asthma a (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.08 to 1.87), history pneumonia (OR, 8.55; 95% CI, 2.07 to 35.26), high levels of airway neutrophils (OR, 8.67; 95% CI, 2.05 to 36.57), airflow obstruction (FEN(1)/FVC) OR, 1.61; 95% CI, 1.21 to 2.14], and atopy (OR, 11.54; 95% CI, 1.97 to 67.70) were identified as independent risk factors associated with the air-trapping phenotype. Conclusions: Quantitative CT-determined air trapping in asthmatic subjects identifies a group of individuals it high risk for severe disease. Several independent risk factors for the presence of this phenotype were identified: perhaps most interestingly, history of Pneumonia, neutrophilic inflammation, and atopy. (CHEST 2009; 135:48-56)	51	125	2009	9	10.1378/chest.08-0049	General & Internal Medicine; Respiratory System
The importance of early complementary feeding in the development of oral tolerance: Concerns and controversies. Rising rates of food allergies in early childhood reflect increasing failure of early immune tolerance mechanisms. There is mounting concern that the current recommended practice of delaying complementary foods until 6 months of age may increase, rather than decrease, the risk of immune disorders. Tolerance to food allergens appears to be driven by regular, early exposure to these proteins during a 'critical early window' of development. Although the timing of this window is not clear in humans, current evidence suggests that this is most likely to be between 4 and 6 months of life and that delayed exposure beyond this period may increase the risk of food allergy, coeliac disease and islet cell autoimmunity. There is also evidence that other factors such as favourable colonization and continued breastfeeding promote tolerance and have protective effects during this period when complementary feeding is initiated. This discussion paper explores the basis for concern over the current recommendation to delay complementary foods as an approach to preventing allergic disease. It will also examine the growing case for introducing complementary foods from around 4 months of age and maintaining breastfeeding during this early feeding period, for at least 6 months if possible.. infant feeding| weaning practices| allergy prevention| growth and development|breast-fed infants| prospective birth cohort| solid food introduction| allergic disease| childhood eczema| celiac-disease| new-zealand| follow-up| prevention| risk.	AUG-2008	infant feeding| weaning practices| allergy prevention| growth and development|breast-fed infants| prospective birth cohort| solid food introduction| allergic disease| childhood eczema| celiac-disease| new-zealand| follow-up| prevention| risk	Prescott, SL; Smith, P; Tang, M; Palmer, DJ; Sinn, J; Huntley, SJ; Cormack, B; Heine, RG; Gibson, RA; Makrides, M	The importance of early complementary feeding in the development of oral tolerance: Concerns and controversies		PEDIATRIC ALLERGY AND IMMUNOLOGY	infant feeding; weaning practices; allergy prevention; growth and development	BREAST-FED INFANTS; PROSPECTIVE BIRTH COHORT; SOLID FOOD INTRODUCTION; ALLERGIC DISEASE; CHILDHOOD ECZEMA; CELIAC-DISEASE; NEW-ZEALAND; FOLLOW-UP; PREVENTION; RISK	Rising rates of food allergies in early childhood reflect increasing failure of early immune tolerance mechanisms. There is mounting concern that the current recommended practice of delaying complementary foods until 6 months of age may increase, rather than decrease, the risk of immune disorders. Tolerance to food allergens appears to be driven by regular, early exposure to these proteins during a 'critical early window' of development. Although the timing of this window is not clear in humans, current evidence suggests that this is most likely to be between 4 and 6 months of life and that delayed exposure beyond this period may increase the risk of food allergy, coeliac disease and islet cell autoimmunity. There is also evidence that other factors such as favourable colonization and continued breastfeeding promote tolerance and have protective effects during this period when complementary feeding is initiated. This discussion paper explores the basis for concern over the current recommendation to delay complementary foods as an approach to preventing allergic disease. It will also examine the growing case for introducing complementary foods from around 4 months of age and maintaining breastfeeding during this early feeding period, for at least 6 months if possible.	34	125	2008	6	10.1111/j.1399-3038.2008.00718.x	Allergy; Immunology; Pediatrics
Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production In vivo. Changes in methylation of CpG sites at the interleukin (IL)-4 and interferon (IFN)-gamma promoters are associated with T helper (Th) 2 polarization in vitro. No previous studies have examined whether air pollution or allergen exposure alters methylation of these two genes in vivo. We hypothesized that diesel exhaust particles (DEP) would induce hypermethylation of the IFN-gamma promoter and hypomethylation of IL-4 in CD4(+) T cells among mice sensitized to the fungus allergen Aspergillus fumigatus. We also hypothesized that DEP-induced methylation changes would affect immunoglobulin (Ig) E regulation. BALB/c mice were exposed to a 3-week course of inhaled DEP exposure while undergoing intranasal sensitization to A. fumigatus. Purified DNA from splenic CD4(+) cells underwent bisulfite treatment, PCR amplification, and pyrosequencing. Sera IgE levels were compared with methylation levels at several CpG sites in the IL-4 and IFN-gamma promoter. Total IgE production was increased following intranasal sensitization A. fumigatus. IgE production was augmented further following combined exposure to A. fumigatus and DEP exposure. Inhaled DEP exposure and intranasal A. fumigatus induced hypermethylation at CpG(-45), CpG(-53), CpG(-205) sites of the IFN-gamma promoter and hypomethylation at CpG(-408) of the IL-4 promoter. Altered methylation of promoters of both genes was correlated significantly with changes in IgE levels. This study is the first to demonstrate that inhaled environmental exposures influence methylation of Th genes in vivo, supporting a new paradigm in asthma pathogenesis.. environmental exposure| respiratory sensitization| cytokines| inhalation toxicology| epigenetic modification.|ifn-gamma gene| cell differentiation| th2 differentiation| air-pollution| expression| promoter| cpg| demethylation| transcription| environment.	MAR-2008	environmental exposure| respiratory sensitization| cytokines| inhalation toxicology| epigenetic modification.|ifn-gamma gene| cell differentiation| th2 differentiation| air-pollution| expression| promoter| cpg| demethylation| transcription| environment	Liu, J; Ballaney, M; Al-Alem, U; Quan, C; Jin, X; Perera, F; Chen, LC; Miller, RL	Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production In vivo		TOXICOLOGICAL SCIENCES	environmental exposure; respiratory sensitization; cytokines; inhalation toxicology; epigenetic modification.	IFN-GAMMA GENE; CELL DIFFERENTIATION; TH2 DIFFERENTIATION; AIR-POLLUTION; EXPRESSION; PROMOTER; CPG; DEMETHYLATION; TRANSCRIPTION; ENVIRONMENT	Changes in methylation of CpG sites at the interleukin (IL)-4 and interferon (IFN)-gamma promoters are associated with T helper (Th) 2 polarization in vitro. No previous studies have examined whether air pollution or allergen exposure alters methylation of these two genes in vivo. We hypothesized that diesel exhaust particles (DEP) would induce hypermethylation of the IFN-gamma promoter and hypomethylation of IL-4 in CD4(+) T cells among mice sensitized to the fungus allergen Aspergillus fumigatus. We also hypothesized that DEP-induced methylation changes would affect immunoglobulin (Ig) E regulation. BALB/c mice were exposed to a 3-week course of inhaled DEP exposure while undergoing intranasal sensitization to A. fumigatus. Purified DNA from splenic CD4(+) cells underwent bisulfite treatment, PCR amplification, and pyrosequencing. Sera IgE levels were compared with methylation levels at several CpG sites in the IL-4 and IFN-gamma promoter. Total IgE production was increased following intranasal sensitization A. fumigatus. IgE production was augmented further following combined exposure to A. fumigatus and DEP exposure. Inhaled DEP exposure and intranasal A. fumigatus induced hypermethylation at CpG(-45), CpG(-53), CpG(-205) sites of the IFN-gamma promoter and hypomethylation at CpG(-408) of the IL-4 promoter. Altered methylation of promoters of both genes was correlated significantly with changes in IgE levels. This study is the first to demonstrate that inhaled environmental exposures influence methylation of Th genes in vivo, supporting a new paradigm in asthma pathogenesis.	32	125	2008	6	10.1093/toxsci/kfm290	Toxicology
Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood. Background: There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age. Objectives: To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children. Methods: Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. Results: In multivariate analyses, early exposure to high levels of dust mite allergen (>= 10 mu g/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% Cl, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages I and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). Conclusion: Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze. Clinical implications: Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children.. endotoxin| dust mite| wheeze| atopy| asthma|day-care attendance| house-dust| 1st year| limulus assay| p-i| children| wheeze| risk| history| infancy.	JUL-2007	endotoxin| dust mite| wheeze| atopy| asthma|day-care attendance| house-dust| 1st year| limulus assay| p-i| children| wheeze| risk| history| infancy	Celedon, JC; Milton, DK; Ramsey, CD; Litonjua, AA; Ryan, L; Platts-Mills, TAE; Gold, DR	Exposure to dust mite allergen and endotoxin in early life and asthma and atopy in childhood		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	endotoxin; dust mite; wheeze; atopy; asthma	DAY-CARE ATTENDANCE; HOUSE-DUST; 1ST YEAR; LIMULUS ASSAY; P-I; CHILDREN; WHEEZE; RISK; HISTORY; INFANCY	Background: There has been no longitudinal study of the relation between concurrent exposure to dust mite allergen and endotoxin in early life and asthma and atopy at school age. Objectives: To examine the relation between exposure to dust mite allergen and endotoxin at age 2 to 3 months and asthma, wheeze, and atopy in high-risk children. Methods: Birth cohort study of 440 children with parental history of atopy in the Boston metropolitan area. Results: In multivariate analyses, early exposure to high levels of dust mite allergen (>= 10 mu g/g) was associated with increased risks of asthma at age 7 years (odds ratio [OR], 3.0; 95% CI, 1.1-7.9) and late-onset wheeze (OR, 5.0; 95% Cl, 1.5-16.4). Exposure to endotoxin levels above the lowest quartile at age 2 to 3 months was associated with reduced odds of atopy at school age (OR, 0.5; 95% CI, 0.2-0.9). In contrast with its inverse association with atopy, endotoxin exposure in early life was associated with an increased risk of any wheeze between ages I and 7 years that did not change significantly with time (hazard ratio for each quartile increment in endotoxin levels, 1.23; 95% CI, 1.07-1.43). Conclusion: Among children at risk of atopy, early exposure to high levels of dust mite allergen is associated with increased risks of asthma and late-onset wheeze. In these children, endotoxin exposure is associated with a reduced risk of atopy but an increased risk of wheeze. Clinical implications: Early endotoxin exposure may be a protective factor against atopy but a risk factor for wheeze in high-risk children.	38	125	2007	6	10.1016/j.jaci.2007.03.037	Allergy; Immunology
"World Trade Center ""sarcoid-like"" granulomatous pulmonary disease in New York city fire department rescue workers. Background: Previous reports suggest that sarcoidosis occurs with abnormally high frequency in firefighters. We sought to determine whether exposure to World Trade Center (WTC) ""dust"" during the collapse and rescue/recovery effort increased the incidence of sarcoidosis or ""sarcoid-like"" granulomatous pulmonary disease (SLGPD). Methods: During the 5 years after the WTC disaster, enrollees in the Fire Department of New York (FDNY) WTC monitoring and treatment programs who had chest radiograph findings suggestive of sarcoidosis underwent evaluation, including the following: chest CT imaging, pulmonary function, provocative challenge, and biopsy. Annual incidence rates were compared to the 15 years before the WTC disaster. Results: After WTC dust exposure, pathologic evidence consistent with new-onset sarcoidosis was found in 26 patients: all 26 patients had intrathoracic adenopathy, and 6 patients (23%) had extrathoracic disease. Thirteen patients were identified during the first year after WTC dust exposure (incidence rate, 86/100,000), and 13 patients were identified during the next 4 years (average annual incidence rate, 22/100,000; as compared to 15/100,000 during the 15 years before the WTC disaster). Eighteen of 26 patients (69%) had findings consistent with asthma. Eight of 21 patients (38%) agreeing to challenge testing had airway hyperreactivity (AHR), findings not seen in FDNY sarcoidosis patients before the WTC disaster. Conclusion: After the WTC disaster, the incidence of sarcoidosis or SLGPD was increased among FDNY rescue workers. This new information about the early onset of WTC-SLGPD and its association with asthma/AHR has important public health consequences for disease prevention, early detection, and treatment following environmental/occupational exposures.. airway hyperreactivity| asthma| emergency medical services workers| firefighters| granulomatous pneumonitis| sarcoidosis| world trade center|bronchial hyperreactivity| airway hyperreactivity| center collapse| risk-factors| center site| firefighters| exposure| pneumonitis| association| involvement."	MAY-2007	airway hyperreactivity| asthma| emergency medical services workers| firefighters| granulomatous pneumonitis| sarcoidosis| world trade center|bronchial hyperreactivity| airway hyperreactivity| center collapse| risk-factors| center site| firefighters| exposure| pneumonitis| association| involvement	Izbicki, G; Chavko, R; Banauch, GI; Weiden, MD; Berger, KI; Aldrich, TK; Hall, C; Kelly, KJ; Prezant, DJ	"World Trade Center ""sarcoid-like"" granulomatous pulmonary disease in New York city fire department rescue workers"		CHEST	airway hyperreactivity; asthma; emergency medical services workers; firefighters; granulomatous pneumonitis; sarcoidosis; World Trade Center	BRONCHIAL HYPERREACTIVITY; AIRWAY HYPERREACTIVITY; CENTER COLLAPSE; RISK-FACTORS; CENTER SITE; FIREFIGHTERS; EXPOSURE; PNEUMONITIS; ASSOCIATION; INVOLVEMENT	"Background: Previous reports suggest that sarcoidosis occurs with abnormally high frequency in firefighters. We sought to determine whether exposure to World Trade Center (WTC) ""dust"" during the collapse and rescue/recovery effort increased the incidence of sarcoidosis or ""sarcoid-like"" granulomatous pulmonary disease (SLGPD). Methods: During the 5 years after the WTC disaster, enrollees in the Fire Department of New York (FDNY) WTC monitoring and treatment programs who had chest radiograph findings suggestive of sarcoidosis underwent evaluation, including the following: chest CT imaging, pulmonary function, provocative challenge, and biopsy. Annual incidence rates were compared to the 15 years before the WTC disaster. Results: After WTC dust exposure, pathologic evidence consistent with new-onset sarcoidosis was found in 26 patients: all 26 patients had intrathoracic adenopathy, and 6 patients (23%) had extrathoracic disease. Thirteen patients were identified during the first year after WTC dust exposure (incidence rate, 86/100,000), and 13 patients were identified during the next 4 years (average annual incidence rate, 22/100,000; as compared to 15/100,000 during the 15 years before the WTC disaster). Eighteen of 26 patients (69%) had findings consistent with asthma. Eight of 21 patients (38%) agreeing to challenge testing had airway hyperreactivity (AHR), findings not seen in FDNY sarcoidosis patients before the WTC disaster. Conclusion: After the WTC disaster, the incidence of sarcoidosis or SLGPD was increased among FDNY rescue workers. This new information about the early onset of WTC-SLGPD and its association with asthma/AHR has important public health consequences for disease prevention, early detection, and treatment following environmental/occupational exposures."	46	125	2007	10	10.1378/chest.06-2114	General & Internal Medicine; Respiratory System
Opposite effects of CD14/-260 on serum IgE levels in children raised in different environments. Background: Most complex diseases are the result of interactions between polymorphisms in the genome and environmental exposures. Objective: We sought to investigate the previously reported association between a polymorphism in the promoter region of CD14 (CD14/-260C -> T) and serum IgE levels in relation to the environment to which children are exposed. Methods: In 624 children living in 2 rural communities in Europe, we compared total and specific serum IgE levels between the genotypes of CD14/-260 in relation to exposure to animals and in relation to house dust endotoxin. Results: We found that the C allele of CD14/-260 was associated with higher levels of both total and specific serum IgE to aeroallergens in children with regular contact with pets, whereas an association in the opposite direction was found in children with regular contact with stable animals. This modifying effect of animal exposure was not explained by levels of house dust endotoxin. However, in children with high levels of house dust endotoxin, the C allele was associated with less specific IgE, independently from animal exposure. Conclusion: Because CD14 is a pattern recognition receptor for microbial molecules, the results suggest that the type and concentrations of such molecules present in the environment strongly determine the direction of the association between CD14/-260 and serum markers of atopy.. serium ige| cd14/-260| microbial exposure| gene-environment interaction|promoter polymorphism| cd14 promoter| c-159t polymorphism| endotoxin levels| mattress dust| soluble cd14| asthma| gene| association| exposure.	SEP-2005	serium ige| cd14/-260| microbial exposure| gene-environment interaction|promoter polymorphism| cd14 promoter| c-159t polymorphism| endotoxin levels| mattress dust| soluble cd14| asthma| gene| association| exposure	Eder, W; Klimecki, W; Yu, LZ; von Mutius, E; Riedler, J; Braun-Fahrlander, C; Nowak, D; Martinez, FD	Opposite effects of CD14/-260 on serum IgE levels in children raised in different environments		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	serium IgE; CD14/-260; microbial exposure; gene-environment interaction	PROMOTER POLYMORPHISM; CD14 PROMOTER; C-159T POLYMORPHISM; ENDOTOXIN LEVELS; MATTRESS DUST; SOLUBLE CD14; ASTHMA; GENE; ASSOCIATION; EXPOSURE	Background: Most complex diseases are the result of interactions between polymorphisms in the genome and environmental exposures. Objective: We sought to investigate the previously reported association between a polymorphism in the promoter region of CD14 (CD14/-260C -> T) and serum IgE levels in relation to the environment to which children are exposed. Methods: In 624 children living in 2 rural communities in Europe, we compared total and specific serum IgE levels between the genotypes of CD14/-260 in relation to exposure to animals and in relation to house dust endotoxin. Results: We found that the C allele of CD14/-260 was associated with higher levels of both total and specific serum IgE to aeroallergens in children with regular contact with pets, whereas an association in the opposite direction was found in children with regular contact with stable animals. This modifying effect of animal exposure was not explained by levels of house dust endotoxin. However, in children with high levels of house dust endotoxin, the C allele was associated with less specific IgE, independently from animal exposure. Conclusion: Because CD14 is a pattern recognition receptor for microbial molecules, the results suggest that the type and concentrations of such molecules present in the environment strongly determine the direction of the association between CD14/-260 and serum markers of atopy.	30	125	2005	7	10.1016/j.jaci.2005.05.003	Allergy; Immunology
Type 2 cytokines in the pathogenesis of sustained airway dysfunction and airway remodeling in mice. The mechanisms underlying airway hyperresponsiveness remain unclear, although airway inflammation and remodeling likely play important roles. We have observed sustained airway hyperreactivity and airway remodeling occurring in mice after chronic allergen exposure and persisting beyond resolution of allergen-induced inflammation. The aim of this study was to delineate mechanisms involved in allergen-induced airway hyperreactivity and airway remodeling and to examine evidence for a causal association between airway remodeling and sustained airway hyperreactivity. Wild-type (WT) and interleukin (IL)-4-, IL-5-, and IL-13-deficient (-/-) mice were sensitized and studied 4 weeks after chronic allergen exposure. By measuring airway responsiveness and airway morphometry, we demonstrated that WT mice developed sustained airway hyperreactivity and aspects of airway remodeling after chronic allergen exposure. Both IL-4(-/-) and IL-13(-/-) mice were protected from developing sustained airway hyperreactivity and aspects of airway remodeling. In contrast, IL-5(-/-) mice developed sustained airway hyperreactivity and aspects of airway remodeling similar to that seen in WT mice. Our results confirm that IL-4 and IL-13, but not IL-5, are critical for the development of sustained airway hyperreactivity and airway remodeling after allergen exposure.. allergic disease| asthma| interleukin-4| interleukin-5| interleukin-13|obstructive pulmonary-disease| allergen-induced increase| murine model| chronic asthma| mild asthma| deficient mice| lung damage| mouse model| inflammation| hyperreactivity.	APR 1-2004	allergic disease| asthma| interleukin-4| interleukin-5| interleukin-13|obstructive pulmonary-disease| allergen-induced increase| murine model| chronic asthma| mild asthma| deficient mice| lung damage| mouse model| inflammation| hyperreactivity	Leigh, R; Ellis, R; Wattlie, JN; Hirota, JA; Matthaei, KI; Foster, PS; O'Byrne, PM; Inman, MD	Type 2 cytokines in the pathogenesis of sustained airway dysfunction and airway remodeling in mice		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	allergic disease; asthma; interleukin-4; interleukin-5; interleukin-13	OBSTRUCTIVE PULMONARY-DISEASE; ALLERGEN-INDUCED INCREASE; MURINE MODEL; CHRONIC ASTHMA; MILD ASTHMA; DEFICIENT MICE; LUNG DAMAGE; MOUSE MODEL; INFLAMMATION; HYPERREACTIVITY	The mechanisms underlying airway hyperresponsiveness remain unclear, although airway inflammation and remodeling likely play important roles. We have observed sustained airway hyperreactivity and airway remodeling occurring in mice after chronic allergen exposure and persisting beyond resolution of allergen-induced inflammation. The aim of this study was to delineate mechanisms involved in allergen-induced airway hyperreactivity and airway remodeling and to examine evidence for a causal association between airway remodeling and sustained airway hyperreactivity. Wild-type (WT) and interleukin (IL)-4-, IL-5-, and IL-13-deficient (-/-) mice were sensitized and studied 4 weeks after chronic allergen exposure. By measuring airway responsiveness and airway morphometry, we demonstrated that WT mice developed sustained airway hyperreactivity and aspects of airway remodeling after chronic allergen exposure. Both IL-4(-/-) and IL-13(-/-) mice were protected from developing sustained airway hyperreactivity and aspects of airway remodeling. In contrast, IL-5(-/-) mice developed sustained airway hyperreactivity and aspects of airway remodeling similar to that seen in WT mice. Our results confirm that IL-4 and IL-13, but not IL-5, are critical for the development of sustained airway hyperreactivity and airway remodeling after allergen exposure.	56	125	2004	8	10.1164/rccm.200305-706OC	General & Internal Medicine; Respiratory System
Indoor air pollution: a global health concern. Indoor air pollution is ubiquitous, and takes many forms, ranging from smoke emitted from solid fuel combustion, especially in households in developing countries, to complex mixtures of volatile and semi-volatile organic compounds present in modern buildings. This paper reviews sources of, and health risks associated with, various indoor chemical pollutants, from a historical and global perspective. Health effects are presented for individual compounds or pollutant mixtures based on real-world exposure situations. Health risks from indoor air pollution are likely to be greatest in cities in developing countries, especially where risks associated with solid fuel combustion coincide with risk associated with modern buildings. Everyday exposure to multiple chemicals, most of which are present indoors, may contribute to increasing prevalence of asthma, autism, childhood cancer, medically unexplained symptoms, and perhaps other illnesses. Given that tobacco consumption and synthetic chemical usage will not be declining at least in the near future, concerns about indoor air pollution may be expected to remain.. volatile organic-compounds| environmental tobacco-smoke| sick building syndrome| developing-countries| passive smoking| parental smoking| lung-cancer| exposure| children| ozone.	2003	volatile organic-compounds| environmental tobacco-smoke| sick building syndrome| developing-countries| passive smoking| parental smoking| lung-cancer| exposure| children| ozone	Zhang, JF; Smith, KR	Indoor air pollution: a global health concern		BRITISH MEDICAL BULLETIN		VOLATILE ORGANIC-COMPOUNDS; ENVIRONMENTAL TOBACCO-SMOKE; SICK BUILDING SYNDROME; DEVELOPING-COUNTRIES; PASSIVE SMOKING; PARENTAL SMOKING; LUNG-CANCER; EXPOSURE; CHILDREN; OZONE	Indoor air pollution is ubiquitous, and takes many forms, ranging from smoke emitted from solid fuel combustion, especially in households in developing countries, to complex mixtures of volatile and semi-volatile organic compounds present in modern buildings. This paper reviews sources of, and health risks associated with, various indoor chemical pollutants, from a historical and global perspective. Health effects are presented for individual compounds or pollutant mixtures based on real-world exposure situations. Health risks from indoor air pollution are likely to be greatest in cities in developing countries, especially where risks associated with solid fuel combustion coincide with risk associated with modern buildings. Everyday exposure to multiple chemicals, most of which are present indoors, may contribute to increasing prevalence of asthma, autism, childhood cancer, medically unexplained symptoms, and perhaps other illnesses. Given that tobacco consumption and synthetic chemical usage will not be declining at least in the near future, concerns about indoor air pollution may be expected to remain.	66	125	2003	17	10.1093/bmb/ldg029	General & Internal Medicine
Carbohydrate epitopes and their relevance for the diagnosis and treatment of allergic diseases. Allergenicity of plant and invertebrate N-glycans has been shown to be caused by the presence of two typical nonmammalian substitutions: an alpha(1,3)-fucose linked to the proximal N-acetylglucosamine and a beta(1,2)-xylose linked to the core mannose. IgE antibodies against these carbohydrate structures are induced upon exposure to pollen or after insect stings, and result in extensive cross-reactivity to plant and invertebrate foods. These cross-reactive IgE antibodies have been shown to possess variable degrees of biological activity, but have never been convincingly shown to induce clinical food allergy. The most likely explanation for this lack of clinical relevance has to be sought in a combination of epitope valency and antibody affinity. In diagnostic tests, these antibodies are at the basis of many false-positive test results for food allergy. Recombinant technologies offer the possibility to produce allergens that do not carry IgE-binding glycans. Whether their absence or presence is of importance for the application of recombinant allergens in immunotherapy is still largely unknown. Copyright (C) 2002 S. Karger AG, Basel.. ige| carbohydrate epitopes| recombinant allergens| diagnostic tests| immunotherapy|yeast pichia-pastoris| basophil histamine-release| aegypti salivary allergen| o-glycosylation codes| ige cross-reactivity| dust mite allergen| recombinant allergens| escherichia-coli| birch pollen| dendritic cells.	NOV-2002	ige| carbohydrate epitopes| recombinant allergens| diagnostic tests| immunotherapy|yeast pichia-pastoris| basophil histamine-release| aegypti salivary allergen| o-glycosylation codes| ige cross-reactivity| dust mite allergen| recombinant allergens| escherichia-coli| birch pollen| dendritic cells	van Ree, R	Carbohydrate epitopes and their relevance for the diagnosis and treatment of allergic diseases		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	IgE; carbohydrate epitopes; recombinant allergens; diagnostic tests; immunotherapy	YEAST PICHIA-PASTORIS; BASOPHIL HISTAMINE-RELEASE; AEGYPTI SALIVARY ALLERGEN; O-GLYCOSYLATION CODES; IGE CROSS-REACTIVITY; DUST MITE ALLERGEN; RECOMBINANT ALLERGENS; ESCHERICHIA-COLI; BIRCH POLLEN; DENDRITIC CELLS	Allergenicity of plant and invertebrate N-glycans has been shown to be caused by the presence of two typical nonmammalian substitutions: an alpha(1,3)-fucose linked to the proximal N-acetylglucosamine and a beta(1,2)-xylose linked to the core mannose. IgE antibodies against these carbohydrate structures are induced upon exposure to pollen or after insect stings, and result in extensive cross-reactivity to plant and invertebrate foods. These cross-reactive IgE antibodies have been shown to possess variable degrees of biological activity, but have never been convincingly shown to induce clinical food allergy. The most likely explanation for this lack of clinical relevance has to be sought in a combination of epitope valency and antibody affinity. In diagnostic tests, these antibodies are at the basis of many false-positive test results for food allergy. Recombinant technologies offer the possibility to produce allergens that do not carry IgE-binding glycans. Whether their absence or presence is of importance for the application of recombinant allergens in immunotherapy is still largely unknown. Copyright (C) 2002 S. Karger AG, Basel.	154	125	2002	9	10.1159/000066770	Allergy; Immunology
Effects of Glutathione-S-Transferase M1, T1, and P1 on childhood lung function growth. The effects of glutathione-S-transferase (GST) M1, GSTT1, and GSTP1 genotypes on lung function growth were investigated in 1,940 children enrolled in the Children's Health Study as fourth graders (aged 8-11 years) in two cohorts during 1993 and 1996 and were followed annually over a 4-year period. Genotypes for GSTM1 and GSTT1 and GSTP1 codon 105variants (ile105 and val105)were determined using DNA from buccal cell specimens. We used two-level regression models to estimate the effects of GSTM1, GSTT1, and GSTP1 genotypes on the adjusted annual average lung function growth. GSTM1 null was associated with deficits in annual growth rates for FVC (-0.21%; 95% confidence interval [Cl], -0.40, 0.03) and FEV1, (-0.27%; 95% Cl, -0.50, -0.04). Children who were homozygous for the GSTP1 val105 allele had slower lung function growth (FVC -0.35%; 95% Cl, -0.62, -0.07; and FEV1 -0.34%; 95% Cl, -0.68, 0.00) than children with one or more ile105 alleles. Children with asthma who were homozygous for the GSTP1 val105 allele had substantially larger deficits in FVC, IFEVI, and maximal mid-expiratory flow than children without asthma. The deficits in FVC and FEV1 growth associated with both GSTM1 null and the GSTP1 val105 allele were largest and were statistically significant in non-Hispanic white children. We conclude that GSTM1 and GSTP1 genotypes are associated with lung function growth in school children.. glutathione-s-transferase| fev| children| polymorphism| growth|obstructive pulmonary-disease| southern california communities| oxidative stress| air-pollution| respiratory symptoms| maternal smoking| supergene family| differing levels| birth-weight| children.	SEP 1-2002	glutathione-s-transferase| fev| children| polymorphism| growth|obstructive pulmonary-disease| southern california communities| oxidative stress| air-pollution| respiratory symptoms| maternal smoking| supergene family| differing levels| birth-weight| children	Gilliland, FD; Gauderman, WJ; Vora, H; Rappaport, E; Dubeau, L	Effects of Glutathione-S-Transferase M1, T1, and P1 on childhood lung function growth		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	glutathione-S-transferase; FEV; children; polymorphism; growth	OBSTRUCTIVE PULMONARY-DISEASE; SOUTHERN CALIFORNIA COMMUNITIES; OXIDATIVE STRESS; AIR-POLLUTION; RESPIRATORY SYMPTOMS; MATERNAL SMOKING; SUPERGENE FAMILY; DIFFERING LEVELS; BIRTH-WEIGHT; CHILDREN	The effects of glutathione-S-transferase (GST) M1, GSTT1, and GSTP1 genotypes on lung function growth were investigated in 1,940 children enrolled in the Children's Health Study as fourth graders (aged 8-11 years) in two cohorts during 1993 and 1996 and were followed annually over a 4-year period. Genotypes for GSTM1 and GSTT1 and GSTP1 codon 105variants (ile105 and val105)were determined using DNA from buccal cell specimens. We used two-level regression models to estimate the effects of GSTM1, GSTT1, and GSTP1 genotypes on the adjusted annual average lung function growth. GSTM1 null was associated with deficits in annual growth rates for FVC (-0.21%; 95% confidence interval [Cl], -0.40, 0.03) and FEV1, (-0.27%; 95% Cl, -0.50, -0.04). Children who were homozygous for the GSTP1 val105 allele had slower lung function growth (FVC -0.35%; 95% Cl, -0.62, -0.07; and FEV1 -0.34%; 95% Cl, -0.68, 0.00) than children with one or more ile105 alleles. Children with asthma who were homozygous for the GSTP1 val105 allele had substantially larger deficits in FVC, IFEVI, and maximal mid-expiratory flow than children without asthma. The deficits in FVC and FEV1 growth associated with both GSTM1 null and the GSTP1 val105 allele were largest and were statistically significant in non-Hispanic white children. We conclude that GSTM1 and GSTP1 genotypes are associated with lung function growth in school children.	48	125	2002	7	10.1164/rccm.2112065	General & Internal Medicine; Respiratory System
Involuntary smoking and asthma severity in children - Data from the Third National Health and Nutrition Examination Survey. Study objectives: We sought to determine the indicators of asthma severity among children in the United States with high and low levels of tobacco smoke exposure. Design: Cross-sectional study. Setting: Nationally representative survey of participants in the Third National Health and Nutrition Examination Survey (from 1988 to 1994). Participants. Five hundred twenty-three children with physician-diagnosed asthma. Measurements and results: We stratified the study participants into tertiles on the basis of serum levels of cotinine (a metabolite of nicotine that indicates tobacco smoke exposure). We used logistic and linear regression modeling, adjusting for known covariates, to determine the effect of high environmental tobacco smoke exposure on the following outcomes: asthma severity (determined using reported symptom and respiratory illness frequency); lung function; physician P visits; and school absence. Among our study sample, 78.6% of children had mild asthma, 6.8% of children bad moderate asthma, and 14.6% of children had severe asthma. Asthmatic children with high levels of smoke exposure, compared with those with low levels of exposure, were more likely to have moderate or severe asthma (odds ratio, 2.7 95% confidence interval [CI], 1.1 to 6.8) and decreased lung function, with a mean FEV1 decrement of 213 mL or 8.1% (95% CI, -14.7 to - 3.5). Conclusions: Involuntary smoke exposure is associated with increased asthma severity and worsened lung function in a nationally representative group of US children with asthma.. asthma| children| tobacco smoke pollution|environmental tobacco-smoke| passive smoking| parental smoking| respiratory health| childhood asthma| united-states| us population| exposure| cotinine.	AUG-2002	asthma| children| tobacco smoke pollution|environmental tobacco-smoke| passive smoking| parental smoking| respiratory health| childhood asthma| united-states| us population| exposure| cotinine	Mannino, DM; Homa, DM; Redd, SC	Involuntary smoking and asthma severity in children - Data from the Third National Health and Nutrition Examination Survey		CHEST	asthma; children; tobacco smoke pollution	ENVIRONMENTAL TOBACCO-SMOKE; PASSIVE SMOKING; PARENTAL SMOKING; RESPIRATORY HEALTH; CHILDHOOD ASTHMA; UNITED-STATES; US POPULATION; EXPOSURE; COTININE	Study objectives: We sought to determine the indicators of asthma severity among children in the United States with high and low levels of tobacco smoke exposure. Design: Cross-sectional study. Setting: Nationally representative survey of participants in the Third National Health and Nutrition Examination Survey (from 1988 to 1994). Participants. Five hundred twenty-three children with physician-diagnosed asthma. Measurements and results: We stratified the study participants into tertiles on the basis of serum levels of cotinine (a metabolite of nicotine that indicates tobacco smoke exposure). We used logistic and linear regression modeling, adjusting for known covariates, to determine the effect of high environmental tobacco smoke exposure on the following outcomes: asthma severity (determined using reported symptom and respiratory illness frequency); lung function; physician P visits; and school absence. Among our study sample, 78.6% of children had mild asthma, 6.8% of children bad moderate asthma, and 14.6% of children had severe asthma. Asthmatic children with high levels of smoke exposure, compared with those with low levels of exposure, were more likely to have moderate or severe asthma (odds ratio, 2.7 95% confidence interval [CI], 1.1 to 6.8) and decreased lung function, with a mean FEV1 decrement of 213 mL or 8.1% (95% CI, -14.7 to - 3.5). Conclusions: Involuntary smoke exposure is associated with increased asthma severity and worsened lung function in a nationally representative group of US children with asthma.	29	125	2002	7	10.1378/chest.122.2.409	General & Internal Medicine; Respiratory System
Are there sensitive subgroups for the effects of airborne particles?. Recent studies have shown that particulate air pollution is a risk factor for hospitalization for heart and lung disease; however, little is known about what subpopulations are most sensitive to this pollutant. We analyzed Medicare hospital admissions for heart disease, chronic obstructive pulmonary disorders (COPD) and pneumonia in Chicago, Cook County, Illinois, between 1985 and 1994. We examined whether previous admissions or secondary diagnoses for selected conditions predisposed persons to having a greater risk from air pollution. We also considered effect modification by age, sex, and race. We found that the air-pollution-associated increase in hospital admissions for cardiovascular diseases was almost doubled in subjects with concurrent respiratory infections. The risk was also increased by a previous admission for conduction disorders. For COPD and pneumonia admissions, diagnosis of conduction disorders or dysrhythmias increased the risk of particulate matter < 10 mu m in aerodynamic diameter (PM10)-associated admissions. Persons with asthma had twice the risk of a PM10-associated pneumonia admission and persons with heart failure had twice the risk of PM10-induced COPD admissions. The PM10 effect did not vary by sex, age, and race. These results suggest that patients with acute respiratory infections or defects in the electrical control of the heart are a risk group for particulate matter effects.. effect modification| hospital admissions| particulate air pollution|particulate air-pollution| clinical comorbidity index| emergency room visits| fly-ash particles| hospital admissions| time-series| respiratory-disease| administrative data| european cities| aphea project.	SEP-2000	effect modification| hospital admissions| particulate air pollution|particulate air-pollution| clinical comorbidity index| emergency room visits| fly-ash particles| hospital admissions| time-series| respiratory-disease| administrative data| european cities| aphea project	Zanobetti, A; Schwartz, J; Gold, D	Are there sensitive subgroups for the effects of airborne particles?		ENVIRONMENTAL HEALTH PERSPECTIVES	effect modification; hospital admissions; particulate air pollution	PARTICULATE AIR-POLLUTION; CLINICAL COMORBIDITY INDEX; EMERGENCY ROOM VISITS; FLY-ASH PARTICLES; HOSPITAL ADMISSIONS; TIME-SERIES; RESPIRATORY-DISEASE; ADMINISTRATIVE DATA; EUROPEAN CITIES; APHEA PROJECT	Recent studies have shown that particulate air pollution is a risk factor for hospitalization for heart and lung disease; however, little is known about what subpopulations are most sensitive to this pollutant. We analyzed Medicare hospital admissions for heart disease, chronic obstructive pulmonary disorders (COPD) and pneumonia in Chicago, Cook County, Illinois, between 1985 and 1994. We examined whether previous admissions or secondary diagnoses for selected conditions predisposed persons to having a greater risk from air pollution. We also considered effect modification by age, sex, and race. We found that the air-pollution-associated increase in hospital admissions for cardiovascular diseases was almost doubled in subjects with concurrent respiratory infections. The risk was also increased by a previous admission for conduction disorders. For COPD and pneumonia admissions, diagnosis of conduction disorders or dysrhythmias increased the risk of particulate matter < 10 mu m in aerodynamic diameter (PM10)-associated admissions. Persons with asthma had twice the risk of a PM10-associated pneumonia admission and persons with heart failure had twice the risk of PM10-induced COPD admissions. The PM10 effect did not vary by sex, age, and race. These results suggest that patients with acute respiratory infections or defects in the electrical control of the heart are a risk group for particulate matter effects.	64	125	2000	5	10.1289/ehp.00108841	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Delayed eosinophil apoptosis in asthma. Background: Eosinophilic inflammation of the airways is a key characteristic of asthma, A defect in apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. Objective: Our purpose was to examine whether the rate of apoptosis differs between peripheral blood eosinophils from asthmatic patients and healthy volunteers, Methods: Peripheral blood was obtained from volunteers with asthma and from control volunteers. Eosinophils were isolated by CD16-negative selection to >99% purity and were cultured for 48 hours, The number of apoptotic eosinophils in the culture was assessed by flow cytometric analysis of relative DNA content in propidium iodide-stained cells. Eosinophil apoptosis is expressed as apoptosis index (number of apoptotic cells/total number of cells). Results: Eosinophils From asthmatic patients not taking steroid medication survived longer (apoptosis index 0.25) than those of healthy control subjects (apoptosis index 0.40, P < .05). In contrast, the rate of apoptosis in eosinophils from patients concurrently taking steroids (apoptosis index 0.46) is higher than that of those not using steroids (P < .01) and not different from that of healthy subjects. To assess whether endogenous IL-3, IL-5, and CM-CSF production contributes to the delayed eosinophil apoptosis, the effects of the corresponding neutralizing antibodies were studied on eosinophil longevity. Neutralization of GM-CSF, but not of IL-3 or IL-5, increased slightly but significantly (P < .01) the rate of apoptosis in eosinophils obtained from patients with asthma, To assess whether beta(2)-agonist medication could contribute to the observed differences, we determined the in vitro effects of albuterol, Fenoterol, and salmeterol on eosinophil apoptosis, All beta(2)-agonists inhibited eosinophil apoptosis by 12% to 19%, A possibility existed that a prior in vivo exposure to IL-5, GM-CSF, or beta(2)-agonists would explain the observed difference. To study this, eosinophils were incubated with GM-CSF, IL-5, and albuterol for 2 to 3 hours, followed by washout of the added compounds, and were subsequently cultured for 48 hours. However, an exposure to GM-CSF (7 pmol/L) or IL-5 (10 pmol/L) for 15 to 180 minutes was not a sufficient signal to prevent eosinophil apoptosis, In contrast, exposure to albuterol (100 nmol/L) for 120 minutes was sufficient to induce a significant (P < .05) decrease in eosinophil apoptosis, Conclusions: The results suggest that eosinophil apoptosis is delayed in asthma, This delay may be partly explained by production of GM-CSF, The in vitro effects of beta(2)-agonists suggest that beta(2)-agonist use might contribute to the prolonged eosinophil survival through inhibition of apoptosis and thus may worsen eosinophilia in asthmatic patients, Use of inhaled glucocorticoids seems to totally reverse the delayed eosinophil apoptosis in asthma.. albuterol| apoptosis| asthma| eosinophil| fenoterol| gm-csf| il-5| salmeterol|human-blood eosinophils| programmed cell-death| in-vitro| gm-csf| survival| macrophages| albuterol| agonists| prolong| il-5.	JUL-2000	albuterol| apoptosis| asthma| eosinophil| fenoterol| gm-csf| il-5| salmeterol|human-blood eosinophils| programmed cell-death| in-vitro| gm-csf| survival| macrophages| albuterol| agonists| prolong| il-5	Kankaanranta, H; Lindsay, MA; Giembycz, MA; Zhang, XZ; Moilanen, E; Barnes, PJ	Delayed eosinophil apoptosis in asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	albuterol; apoptosis; asthma; eosinophil; fenoterol; GM-CSF; IL-5; salmeterol	HUMAN-BLOOD EOSINOPHILS; PROGRAMMED CELL-DEATH; IN-VITRO; GM-CSF; SURVIVAL; MACROPHAGES; ALBUTEROL; AGONISTS; PROLONG; IL-5	Background: Eosinophilic inflammation of the airways is a key characteristic of asthma, A defect in apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. Objective: Our purpose was to examine whether the rate of apoptosis differs between peripheral blood eosinophils from asthmatic patients and healthy volunteers, Methods: Peripheral blood was obtained from volunteers with asthma and from control volunteers. Eosinophils were isolated by CD16-negative selection to >99% purity and were cultured for 48 hours, The number of apoptotic eosinophils in the culture was assessed by flow cytometric analysis of relative DNA content in propidium iodide-stained cells. Eosinophil apoptosis is expressed as apoptosis index (number of apoptotic cells/total number of cells). Results: Eosinophils From asthmatic patients not taking steroid medication survived longer (apoptosis index 0.25) than those of healthy control subjects (apoptosis index 0.40, P < .05). In contrast, the rate of apoptosis in eosinophils from patients concurrently taking steroids (apoptosis index 0.46) is higher than that of those not using steroids (P < .01) and not different from that of healthy subjects. To assess whether endogenous IL-3, IL-5, and CM-CSF production contributes to the delayed eosinophil apoptosis, the effects of the corresponding neutralizing antibodies were studied on eosinophil longevity. Neutralization of GM-CSF, but not of IL-3 or IL-5, increased slightly but significantly (P < .01) the rate of apoptosis in eosinophils obtained from patients with asthma, To assess whether beta(2)-agonist medication could contribute to the observed differences, we determined the in vitro effects of albuterol, Fenoterol, and salmeterol on eosinophil apoptosis, All beta(2)-agonists inhibited eosinophil apoptosis by 12% to 19%, A possibility existed that a prior in vivo exposure to IL-5, GM-CSF, or beta(2)-agonists would explain the observed difference. To study this, eosinophils were incubated with GM-CSF, IL-5, and albuterol for 2 to 3 hours, followed by washout of the added compounds, and were subsequently cultured for 48 hours. However, an exposure to GM-CSF (7 pmol/L) or IL-5 (10 pmol/L) for 15 to 180 minutes was not a sufficient signal to prevent eosinophil apoptosis, In contrast, exposure to albuterol (100 nmol/L) for 120 minutes was sufficient to induce a significant (P < .05) decrease in eosinophil apoptosis, Conclusions: The results suggest that eosinophil apoptosis is delayed in asthma, This delay may be partly explained by production of GM-CSF, The in vitro effects of beta(2)-agonists suggest that beta(2)-agonist use might contribute to the prolonged eosinophil survival through inhibition of apoptosis and thus may worsen eosinophilia in asthmatic patients, Use of inhaled glucocorticoids seems to totally reverse the delayed eosinophil apoptosis in asthma.	28	125	2000	7		Allergy; Immunology
Respiratory fungal allergy. Fungal allergy including allergic rhinitis, conjunctivitis, bronchial asthma, and allergic bronchopulmonary mycoses results from exposure to spores. In this review are have dealt with the common allergenic fungi and allergens, immunopathogenesis, diagnostic assays, and the possible control of allergy in the future based on epitope-specific immunotherapy and vaccination. (C) 2000 Editions scientifiques et medicales Elsevier SAS.. fungal allergens| ige antibody| recombinant allergens| elisa| western blot|aspergillus-fumigatus allergens| alkaline serine proteinase| major allergen| bronchopulmonary aspergillosis| cladosporium-herbarum| mold allergy| alternaria-alternata| penicillium-citrinum| asthmatic-patients| immune-responses.	JUL-2000	fungal allergens| ige antibody| recombinant allergens| elisa| western blot|aspergillus-fumigatus allergens| alkaline serine proteinase| major allergen| bronchopulmonary aspergillosis| cladosporium-herbarum| mold allergy| alternaria-alternata| penicillium-citrinum| asthmatic-patients| immune-responses	Kurup, VP; Shen, HD; Banerjee, B	Respiratory fungal allergy		MICROBES AND INFECTION	fungal allergens; IgE antibody; recombinant allergens; ELISA; Western blot	ASPERGILLUS-FUMIGATUS ALLERGENS; ALKALINE SERINE PROTEINASE; MAJOR ALLERGEN; BRONCHOPULMONARY ASPERGILLOSIS; CLADOSPORIUM-HERBARUM; MOLD ALLERGY; ALTERNARIA-ALTERNATA; PENICILLIUM-CITRINUM; ASTHMATIC-PATIENTS; IMMUNE-RESPONSES	Fungal allergy including allergic rhinitis, conjunctivitis, bronchial asthma, and allergic bronchopulmonary mycoses results from exposure to spores. In this review are have dealt with the common allergenic fungi and allergens, immunopathogenesis, diagnostic assays, and the possible control of allergy in the future based on epitope-specific immunotherapy and vaccination. (C) 2000 Editions scientifiques et medicales Elsevier SAS.	59	125	2000	10	10.1016/S1286-4579(00)01264-8	Immunology; Infectious Diseases; Microbiology
Gene-environment interaction in the onset of eczema in infancy: Filaggrin loss-of-function mutations enhanced by neonatal cat exposure. Background Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures ( pets and dust mites) in relation to the development of eczema. Methods and Findings We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life ( hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05), but not related to FLG genotype. In Manchester ( n 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35-10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. Conclusions We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.. atopic-dermatitis| ichthyosis vulgaris| childhood asthma| birth cohort| risk| life| sensitization| predispose| diagnosis| allergens.	JUN-2008	atopic-dermatitis| ichthyosis vulgaris| childhood asthma| birth cohort| risk| life| sensitization| predispose| diagnosis| allergens	Bisgaard, H; Simpson, A; Palmer, CNA; Bonnelykke, K; Mclean, I; Mukhopadhyay, S; Pipper, CB; Halkjaer, LB; Lipworth, B; Hankinson, J; Woodcock, A; Custovic, A	Gene-environment interaction in the onset of eczema in infancy: Filaggrin loss-of-function mutations enhanced by neonatal cat exposure		PLOS MEDICINE		ATOPIC-DERMATITIS; ICHTHYOSIS VULGARIS; CHILDHOOD ASTHMA; BIRTH COHORT; RISK; LIFE; SENSITIZATION; PREDISPOSE; DIAGNOSIS; ALLERGENS	Background Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures ( pets and dust mites) in relation to the development of eczema. Methods and Findings We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life ( hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27-4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79-32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24-1.01, p = 0.05), but not related to FLG genotype. In Manchester ( n 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13-3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35-10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16-2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation. Conclusions We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.	20	124	2008	6	10.1371/journal.pmed.0050131	General & Internal Medicine
Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma. Dendritic cells ( DCs) are integral to the differentiation of T helper cells into T helper type 1 T(H)1, T(H)2 and T(H)17 subsets. Interleukin-6 ( IL-6) plays an important part in regulating these three arms of the immune response by limiting the T(H)1 response and promoting the T(H)2 and T(H)17 responses. In this study, we investigated pathways in DCs that promote IL-6 production. We show that the allergen house dust mite ( HDM) or the mucosal adjuvant cholera toxin promotes cell surface expression of c-Kit and its ligand, stem cell factor ( SCF), on DCs. This dual upregulation of c-Kit and SCF results in sustained signaling downstream of c-Kit, promoting IL-6 secretion. Intranasal administration of antigen into c-Kit-mutant mice or neutralization of IL-6 in cultures established from the lung-draining lymph nodes of immunized wild-type mice blunted the T(H)2 and T(H)17 responses. DCs lacking functional c-Kit or those unable to express membrane-bound SCF secreted lower amounts of IL- 6 in response to HDM or cholera toxin. DCs expressing nonfunctional c-Kit were unable to induce a robust T(H)2 or T(H)17 response and elicited diminished allergic airway inflammation when adoptively transferred into mice. Expression of the Notch ligand Jagged-2, which has been associated with T(H)2 differentiation, was blunted in DCs from c-Kit-mutant mice. c-Kit upregulation was specifically induced by T(H)2- and T(H)17-skewing stimuli, as the T(H)1-inducing adjuvant, CpG oligodeoxynucleotide, did not promote either c-Kit or Jagged-2 expression. DCs generated from mice expressing a catalytically inactive form of the p110 delta subunit of phosphatidylinositol-3 ( PI3) kinase ( p110(D910A)) secreted lower amounts of IL-6 upon stimulation with cholera toxin. Collectively, these results highlight the importance of the c-Kit-PI3 kinase-IL-6 signaling axis in DCs in regulating T cell responses.. transcription factor gata-3| bound tgf-beta| airway inflammation| mast-cells| proto-oncogene| cholera-toxin| growth-factor| w-locus| expression| responses.	MAY-2008	transcription factor gata-3| bound tgf-beta| airway inflammation| mast-cells| proto-oncogene| cholera-toxin| growth-factor| w-locus| expression| responses	Krishnamoorthy, N; Oriss, TB; Paglia, M; Fei, MJ; Yarlagadda, M; Vanhaesebroeck, B; Ray, A; Ray, P	Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma		NATURE MEDICINE		TRANSCRIPTION FACTOR GATA-3; BOUND TGF-BETA; AIRWAY INFLAMMATION; MAST-CELLS; PROTO-ONCOGENE; CHOLERA-TOXIN; GROWTH-FACTOR; W-LOCUS; EXPRESSION; RESPONSES	Dendritic cells ( DCs) are integral to the differentiation of T helper cells into T helper type 1 T(H)1, T(H)2 and T(H)17 subsets. Interleukin-6 ( IL-6) plays an important part in regulating these three arms of the immune response by limiting the T(H)1 response and promoting the T(H)2 and T(H)17 responses. In this study, we investigated pathways in DCs that promote IL-6 production. We show that the allergen house dust mite ( HDM) or the mucosal adjuvant cholera toxin promotes cell surface expression of c-Kit and its ligand, stem cell factor ( SCF), on DCs. This dual upregulation of c-Kit and SCF results in sustained signaling downstream of c-Kit, promoting IL-6 secretion. Intranasal administration of antigen into c-Kit-mutant mice or neutralization of IL-6 in cultures established from the lung-draining lymph nodes of immunized wild-type mice blunted the T(H)2 and T(H)17 responses. DCs lacking functional c-Kit or those unable to express membrane-bound SCF secreted lower amounts of IL- 6 in response to HDM or cholera toxin. DCs expressing nonfunctional c-Kit were unable to induce a robust T(H)2 or T(H)17 response and elicited diminished allergic airway inflammation when adoptively transferred into mice. Expression of the Notch ligand Jagged-2, which has been associated with T(H)2 differentiation, was blunted in DCs from c-Kit-mutant mice. c-Kit upregulation was specifically induced by T(H)2- and T(H)17-skewing stimuli, as the T(H)1-inducing adjuvant, CpG oligodeoxynucleotide, did not promote either c-Kit or Jagged-2 expression. DCs generated from mice expressing a catalytically inactive form of the p110 delta subunit of phosphatidylinositol-3 ( PI3) kinase ( p110(D910A)) secreted lower amounts of IL-6 upon stimulation with cholera toxin. Collectively, these results highlight the importance of the c-Kit-PI3 kinase-IL-6 signaling axis in DCs in regulating T cell responses.	49	124	2008	9	10.1038/nm1766	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Characteristics of intermittent and persistent allergic rhinitis: DREAMS study group. Background In the Allergic Rhinitis and its Impact on Asthma ( ARIA) classification, intermittent and persistent rhinitis were proposed to replace seasonal and perennial allergic rhinitis (AR). Aim To better understand the ARIA classification of rhinitis. Methods A cross-sectional study was carried out in 591 patients consulting ENT or allergy specialists for AR and 502 control subjects. The diagnosis of AR was based on a score for allergic rhinitis (SFAR) >= 7. Patients were classified according to the four ARIA classes ( mild intermittent, mild persistent, moderate/severe intermittent and moderate/severe persistent). Allergen sensitization (skin prick tests (SPTs) or specific IgE) and co- morbidities were examined according to the ARIA classes. Results Ten percent of patients had mild intermittent rhinitis, 14% mild persistent rhinitis, 17% moderate/severe intermittent rhinitis and 59% moderate/severe persistent rhinitis. Most patients with intermittent rhinitis had a pollen sensitivity, but 5% had a single house dust mite (HDM) sensitization. Over 50% of patients with persistent rhinitis were allergic to pollens or HDM. Asthma was present in 24% of rhinitis patients and in only 2% of the control population ( P < 0.0001). Patients with moderate/severe persistent rhinitis had the highest asthma prevalence (33%). Discussion Intermittent and persistent rhinitis are not synonymous of seasonal and perennial rhinitis. Most patients consulting specialists have severe rhinitis. Asthma prevalence increases with duration and severity of rhinitis supporting the ARIA major recommendation that patients with persistent rhinitis should be evaluated for asthma.. allergy| aria| asthma| rhinitis|skin prick tests| perennial rhinitis| asthma| population| pollen| validation| adults| atopy| questionnaire| heterogeneity.	JUN-2005	allergy| aria| asthma| rhinitis|skin prick tests| perennial rhinitis| asthma| population| pollen| validation| adults| atopy| questionnaire| heterogeneity	Bousquet, J; Annesi-Maesano, I; Carat, F; Leger, D; Rugina, M; Pribil, C; El Hasnaoui, A; Chanal, I	Characteristics of intermittent and persistent allergic rhinitis: DREAMS study group		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; ARIA; asthma; rhinitis	SKIN PRICK TESTS; PERENNIAL RHINITIS; ASTHMA; POPULATION; POLLEN; VALIDATION; ADULTS; ATOPY; QUESTIONNAIRE; HETEROGENEITY	Background In the Allergic Rhinitis and its Impact on Asthma ( ARIA) classification, intermittent and persistent rhinitis were proposed to replace seasonal and perennial allergic rhinitis (AR). Aim To better understand the ARIA classification of rhinitis. Methods A cross-sectional study was carried out in 591 patients consulting ENT or allergy specialists for AR and 502 control subjects. The diagnosis of AR was based on a score for allergic rhinitis (SFAR) >= 7. Patients were classified according to the four ARIA classes ( mild intermittent, mild persistent, moderate/severe intermittent and moderate/severe persistent). Allergen sensitization (skin prick tests (SPTs) or specific IgE) and co- morbidities were examined according to the ARIA classes. Results Ten percent of patients had mild intermittent rhinitis, 14% mild persistent rhinitis, 17% moderate/severe intermittent rhinitis and 59% moderate/severe persistent rhinitis. Most patients with intermittent rhinitis had a pollen sensitivity, but 5% had a single house dust mite (HDM) sensitization. Over 50% of patients with persistent rhinitis were allergic to pollens or HDM. Asthma was present in 24% of rhinitis patients and in only 2% of the control population ( P < 0.0001). Patients with moderate/severe persistent rhinitis had the highest asthma prevalence (33%). Discussion Intermittent and persistent rhinitis are not synonymous of seasonal and perennial rhinitis. Most patients consulting specialists have severe rhinitis. Asthma prevalence increases with duration and severity of rhinitis supporting the ARIA major recommendation that patients with persistent rhinitis should be evaluated for asthma.	30	124	2005	5	10.1111/j.1365-2222.2005.02274.x	Allergy; Immunology
(1 -> 3)-beta-D-glucans and respiratory health: a review of the scientific evidence. (1 -> 3)-beta-D-glucan are non-allergenic structural cell wall components of most fungi that have been suggested to play a causal role in the development of respiratory symptoms associated with indoor fungal exposure. This review describes the currently available epidemiological literature on health effects of (1 -> 3)-beta-D-glucan, focusing on atopy, airway inflammation and symptoms, asthma, and lung function. In addition to population studies, studies in human volunteers experimentally exposed to (1 -> 3)-beta-D-glucan are described as well as relevant animal studies. Furthermore, the review discusses exposure assessment methods, the potential for exposure control and it concludes with identifying research needs. The observational and experimental studies reviewed suggested some association between (1 -> 3)-beta-D-glucan exposure, airway inflammation and symptoms, however, results were mixed and specific symptoms and potential underlying inflammatory mechanisms associated with exposure could not be identified. Large observational studies using well validated exposure assessment methods are needed to further our knowledge regarding the potential health effects of indoor (1 -> 3)-beta-D-glucan exposure.. (1 -> 3)-beta-d-glucan| review| respiratory health| fungi| damp| epidemiology|upper airway inflammation| in-house dust| work-related symptoms| mold exposure| pulmonary inflammation| personal exposures| allergic response| waste collectors| cytokine release| soluble glucan.	JUN-2005	(1 -> 3)-beta-d-glucan| review| respiratory health| fungi| damp| epidemiology|upper airway inflammation| in-house dust| work-related symptoms| mold exposure| pulmonary inflammation| personal exposures| allergic response| waste collectors| cytokine release| soluble glucan	Douwes, J	(1 -> 3)-beta-D-glucans and respiratory health: a review of the scientific evidence		INDOOR AIR	(1 -> 3)-beta-D-glucan; review; respiratory health; fungi; damp; epidemiology	UPPER AIRWAY INFLAMMATION; IN-HOUSE DUST; WORK-RELATED SYMPTOMS; MOLD EXPOSURE; PULMONARY INFLAMMATION; PERSONAL EXPOSURES; ALLERGIC RESPONSE; WASTE COLLECTORS; CYTOKINE RELEASE; SOLUBLE GLUCAN	(1 -> 3)-beta-D-glucan are non-allergenic structural cell wall components of most fungi that have been suggested to play a causal role in the development of respiratory symptoms associated with indoor fungal exposure. This review describes the currently available epidemiological literature on health effects of (1 -> 3)-beta-D-glucan, focusing on atopy, airway inflammation and symptoms, asthma, and lung function. In addition to population studies, studies in human volunteers experimentally exposed to (1 -> 3)-beta-D-glucan are described as well as relevant animal studies. Furthermore, the review discusses exposure assessment methods, the potential for exposure control and it concludes with identifying research needs. The observational and experimental studies reviewed suggested some association between (1 -> 3)-beta-D-glucan exposure, airway inflammation and symptoms, however, results were mixed and specific symptoms and potential underlying inflammatory mechanisms associated with exposure could not be identified. Large observational studies using well validated exposure assessment methods are needed to further our knowledge regarding the potential health effects of indoor (1 -> 3)-beta-D-glucan exposure.	64	124	2005	10	10.1111/j.1600-0668.2005.00333.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Persistent hyperreactivity and reactive airway dysfunction in firefighters at the World Trade Center. New York City Fire Department rescue workers experienced massive exposure to airborne particulates at the World Trade Center site. Aims of this longitudinal study were to (1) determine if bronchial hyperreactivity was present, persistent, and independently associated with exposure intensity, (2) identify objective measures shortly after the collapse that would predict persistent hyperreactivity and a diagnosis of reactive airways dysfunction 6 months post-collapse. A representative sample of 179 rescue workers stratified by exposure intensity (high, moderate, and control) without current smoking or prior respiratory disease was enrolled. Highly exposed workers arrived within 2 hours of collapse, moderately exposed workers arrived later on Days 1-2; control subjects were not exposed. Hyperreactivity at 1, 3, and 6 months post-collapse was associated with exposure intensity, independent of ex-smoking and airflow obstruction. Six months post-collapse, highly exposed workers were 6.8 times more likely than moderately exposed workers and control subjects to be hyperreactive (95% confidence interval, 1.8-25.2; p = 0.004), and hyperreactivity persisted in 55% of those hyperreactive at I and/or 3 months. In highly exposed subjects, hyperreactivity 1 or 3 months post-collapse was the sole predictor for reactive airways dysfunction (p = 0.021). In conclusion, development and persistence of hyperreactivity and reactive airways dysfunction were strongly and independently associated with exposure intensity. Hyperreactivity shortly post-collapse predicted reactive airways dysfunction at 6 months in highly exposed workers; this has important implications for disaster management.. inorganic particulate matter| nonspecific bronchial hyperreactivity| reactive airways dysfunction syndrome| firefighters| world trade center collapse|dose-response curves| bronchial responsiveness| occupational asthma| follow-up| health consequences| population-sample| smoke-inhalation| syndrome rads| lung-function| exposure.	JUL 1-2003	inorganic particulate matter| nonspecific bronchial hyperreactivity| reactive airways dysfunction syndrome| firefighters| world trade center collapse|dose-response curves| bronchial responsiveness| occupational asthma| follow-up| health consequences| population-sample| smoke-inhalation| syndrome rads| lung-function| exposure	Banauch, GI; Alleyne, D; Sanchez, R; Olender, K; Cohen, HW; Weiden, M; Kelly, KJ; Prezant, DJ	Persistent hyperreactivity and reactive airway dysfunction in firefighters at the World Trade Center		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	inorganic particulate matter; nonspecific bronchial hyperreactivity; reactive airways dysfunction syndrome; firefighters; World Trade Center collapse	DOSE-RESPONSE CURVES; BRONCHIAL RESPONSIVENESS; OCCUPATIONAL ASTHMA; FOLLOW-UP; HEALTH CONSEQUENCES; POPULATION-SAMPLE; SMOKE-INHALATION; SYNDROME RADS; LUNG-FUNCTION; EXPOSURE	New York City Fire Department rescue workers experienced massive exposure to airborne particulates at the World Trade Center site. Aims of this longitudinal study were to (1) determine if bronchial hyperreactivity was present, persistent, and independently associated with exposure intensity, (2) identify objective measures shortly after the collapse that would predict persistent hyperreactivity and a diagnosis of reactive airways dysfunction 6 months post-collapse. A representative sample of 179 rescue workers stratified by exposure intensity (high, moderate, and control) without current smoking or prior respiratory disease was enrolled. Highly exposed workers arrived within 2 hours of collapse, moderately exposed workers arrived later on Days 1-2; control subjects were not exposed. Hyperreactivity at 1, 3, and 6 months post-collapse was associated with exposure intensity, independent of ex-smoking and airflow obstruction. Six months post-collapse, highly exposed workers were 6.8 times more likely than moderately exposed workers and control subjects to be hyperreactive (95% confidence interval, 1.8-25.2; p = 0.004), and hyperreactivity persisted in 55% of those hyperreactive at I and/or 3 months. In highly exposed subjects, hyperreactivity 1 or 3 months post-collapse was the sole predictor for reactive airways dysfunction (p = 0.021). In conclusion, development and persistence of hyperreactivity and reactive airways dysfunction were strongly and independently associated with exposure intensity. Hyperreactivity shortly post-collapse predicted reactive airways dysfunction at 6 months in highly exposed workers; this has important implications for disaster management.	48	124	2003	9	10.1164/rccm.200211-1329OC	General & Internal Medicine; Respiratory System
Effect of continuing or finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma: A 5-year prospective follow-up study of 42 highly trained swimmers. Background: Mild eosinophilic airway inflammation and bronchial hyperresponsiveness-ie, mild asthma-have been shown to affect a high proportion of endurance athletes. The persistence of airway inflammation, bronchial hyperresponsiveness, and asthma in this population is not known, however, inasmuch as follow-up studies of athletes' asthma have not been performed. Objective: The purpose of this study was to investigate effect of finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma. Methods: Forty-two elite competitive swimmers, most of them from the Finnish national team (37/42; 88%), were followed for 5 years in a prospective manner. All of the swimmers completed questionnaires and underwent resting spirometry, histamine challenge testing, and skin prick tests at baseline and at follow-up. Twenty-nine swimmers (69%) also gave induced sputum samples on both occasions. Sixteen (38%) of the swimmers had continued their competitive careers during follow-up (active swimmers), but 26 (62%) had stopped competing more than 3 months before the follow-up examination (past swimmers). Results: Bronchial responsiveness was increased in 7 (44%) of the 16 active swimmers at baseline and in 8 (50%) of the 16 active swimmers at follow-up; it was increased in 8 (31%) of the 26 past swimmers at baseline and in 3 (12%) of the 26 past swimmers at follow-up (McNemar test, P = .025). The difference in the change in bronchial hyperresponsiveness between the study groups was significant (likelihood ratio test, P = .023). Current asthma (defined as bronchial hyperresponsiveness and exercise-induced bronchial symptoms monthly) was observed in 5 (31%) of the active swimmers at baseline and in 7 (44%) of the active swimmers at follow-up; of the past swimmers, it occurred in 6 (23%) at baseline and in 1 (4%) at follow-up (McNemar test, P = .025). The difference in the change in current asthma between the study groups was significant (likelihood ratio test, P = .0040). The sputum differential cell counts of eosinophils and lymphocytes increased significantly during the follow-up period in the active swimmers (Wilcoxon signed rank sum test; P = .033 and P = .0029, respectively); in the past swimmers, the sputum differential cell counts of eosinophils tended to decrease during the follow-up period (P = .17), whereas the differential cell counts of lymphocytes did not change significantly. The changes in the sputum differential cell counts of eosinophils between the study groups differed significantly (Mann-Whitney U test, P = .019). Conclusion: In swimmers who had stopped high-level training, bronchial hyperresponsiveness and asthma attenuated or even disappeared. Mild eosinophilic airway inflammation was aggravated among highly trained swimmers who remained active during the 5-year follow-up. Our results suggest that athletes' asthma is partly reversible and that it may develop during and subside after an active sports career.. asthma| athletes| airway inflammation| bronchial hyperresponsiveness| swimming| sports medicine|cross-country skiers| induced sputum| prevalence| responsiveness| exposure| risk.	JUN-2002	asthma| athletes| airway inflammation| bronchial hyperresponsiveness| swimming| sports medicine|cross-country skiers| induced sputum| prevalence| responsiveness| exposure| risk	Helenius, I; Rytila, P; Sarna, S; Lumme, A; Helenius, M; Remes, V; Haahtela, T	Effect of continuing or finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma: A 5-year prospective follow-up study of 42 highly trained swimmers		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; athletes; airway inflammation; bronchial hyperresponsiveness; swimming; sports medicine	CROSS-COUNTRY SKIERS; INDUCED SPUTUM; PREVALENCE; RESPONSIVENESS; EXPOSURE; RISK	Background: Mild eosinophilic airway inflammation and bronchial hyperresponsiveness-ie, mild asthma-have been shown to affect a high proportion of endurance athletes. The persistence of airway inflammation, bronchial hyperresponsiveness, and asthma in this population is not known, however, inasmuch as follow-up studies of athletes' asthma have not been performed. Objective: The purpose of this study was to investigate effect of finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma. Methods: Forty-two elite competitive swimmers, most of them from the Finnish national team (37/42; 88%), were followed for 5 years in a prospective manner. All of the swimmers completed questionnaires and underwent resting spirometry, histamine challenge testing, and skin prick tests at baseline and at follow-up. Twenty-nine swimmers (69%) also gave induced sputum samples on both occasions. Sixteen (38%) of the swimmers had continued their competitive careers during follow-up (active swimmers), but 26 (62%) had stopped competing more than 3 months before the follow-up examination (past swimmers). Results: Bronchial responsiveness was increased in 7 (44%) of the 16 active swimmers at baseline and in 8 (50%) of the 16 active swimmers at follow-up; it was increased in 8 (31%) of the 26 past swimmers at baseline and in 3 (12%) of the 26 past swimmers at follow-up (McNemar test, P = .025). The difference in the change in bronchial hyperresponsiveness between the study groups was significant (likelihood ratio test, P = .023). Current asthma (defined as bronchial hyperresponsiveness and exercise-induced bronchial symptoms monthly) was observed in 5 (31%) of the active swimmers at baseline and in 7 (44%) of the active swimmers at follow-up; of the past swimmers, it occurred in 6 (23%) at baseline and in 1 (4%) at follow-up (McNemar test, P = .025). The difference in the change in current asthma between the study groups was significant (likelihood ratio test, P = .0040). The sputum differential cell counts of eosinophils and lymphocytes increased significantly during the follow-up period in the active swimmers (Wilcoxon signed rank sum test; P = .033 and P = .0029, respectively); in the past swimmers, the sputum differential cell counts of eosinophils tended to decrease during the follow-up period (P = .17), whereas the differential cell counts of lymphocytes did not change significantly. The changes in the sputum differential cell counts of eosinophils between the study groups differed significantly (Mann-Whitney U test, P = .019). Conclusion: In swimmers who had stopped high-level training, bronchial hyperresponsiveness and asthma attenuated or even disappeared. Mild eosinophilic airway inflammation was aggravated among highly trained swimmers who remained active during the 5-year follow-up. Our results suggest that athletes' asthma is partly reversible and that it may develop during and subside after an active sports career.	28	124	2002	7	10.1067/mai.2002.124769	Allergy; Immunology
Health care use and costs for children with attention-deficit/hyperactivity disorder - National estimates front the Medical Expenditure Panel Survey. Context: Although attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent chronic condition of childhood, little is known about patterns of health care use and associated expenditures. Objective: To compare health care use and costs among children with ADHD, children with asthma, and the general pediatric population. Design and Setting: The 1996 Medical Expenditure Panel Survey, a nationally representative household survey. Participants: All 5439 children aged 5 to 20 years from the 1996 Medical Expenditure Panel Survey were included in this analysis. Children who had ADHD, asthma,d or neither (general population) were identified from Into-national Classification of Diseases, Ninth Revision, Clinical Modification codes and prescription records. Main Outcome Measures: Mean health care use (outpatient visits, emergency department visits, hospital stays, home health visit days, and prescriptions) and associated expenditures. Results: We identified 105 children with ADHD, 322 with asthma, and 4052 with neither diagnosis. Children with ADHD had significantly higher mean total health care costs ($1151) compared with children with asthma ($1091 P<.05) and the general population ($712 P<.001). After adjusting for age, Sex, race, household income, access to care, parent education, and martial Status, excess total costs were $479 for children with ADHD (P<.001) and $437 for children with asthma (P<.01). Conclusions: Overall costs of care for children with ADHD are comparable to costs for children with asthma and significantly greater than for the general pediatric Population, Specific types of health care use and the sources of expenditures differ between children with ADHD and children with asthma. Because much ADHD-related care occurs within school and mental health settings, these figures likely underestimate the true costs of caring for children with this condition.. deficit hyperactivity disorder| county-wide sample| psychosocial problems| asthma| identification| adolescents| management| patterns| criteria.	MAY-2002	deficit hyperactivity disorder| county-wide sample| psychosocial problems| asthma| identification| adolescents| management| patterns| criteria	Chan, E; Zhan, CL; Homer, CJ	Health care use and costs for children with attention-deficit/hyperactivity disorder - National estimates front the Medical Expenditure Panel Survey		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		DEFICIT HYPERACTIVITY DISORDER; COUNTY-WIDE SAMPLE; PSYCHOSOCIAL PROBLEMS; ASTHMA; IDENTIFICATION; ADOLESCENTS; MANAGEMENT; PATTERNS; CRITERIA	Context: Although attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent chronic condition of childhood, little is known about patterns of health care use and associated expenditures. Objective: To compare health care use and costs among children with ADHD, children with asthma, and the general pediatric population. Design and Setting: The 1996 Medical Expenditure Panel Survey, a nationally representative household survey. Participants: All 5439 children aged 5 to 20 years from the 1996 Medical Expenditure Panel Survey were included in this analysis. Children who had ADHD, asthma,d or neither (general population) were identified from Into-national Classification of Diseases, Ninth Revision, Clinical Modification codes and prescription records. Main Outcome Measures: Mean health care use (outpatient visits, emergency department visits, hospital stays, home health visit days, and prescriptions) and associated expenditures. Results: We identified 105 children with ADHD, 322 with asthma, and 4052 with neither diagnosis. Children with ADHD had significantly higher mean total health care costs ($1151) compared with children with asthma ($1091 P<.05) and the general population ($712 P<.001). After adjusting for age, Sex, race, household income, access to care, parent education, and martial Status, excess total costs were $479 for children with ADHD (P<.001) and $437 for children with asthma (P<.01). Conclusions: Overall costs of care for children with ADHD are comparable to costs for children with asthma and significantly greater than for the general pediatric Population, Specific types of health care use and the sources of expenditures differ between children with ADHD and children with asthma. Because much ADHD-related care occurs within school and mental health settings, these figures likely underestimate the true costs of caring for children with this condition.	27	124	2002	8		Pediatrics
Dust mite, cockroach, cat, and dog allergen concentrations in homes of asthmatic children in the northeastern United States: Impact of socioeconomic factors and population density. Home exposures to aeroallergens are an important environmental factor in allergic sensitization and in the development and exacerbation of asthma. We assessed variations in home concentrations of dust Mite, cock-roach, cat, and dog allergens in dust collected in the main living areas of asthmatics' homes by family income, mother's education, dwelling type, population density, household population density, and ethnicity in Connecticut and south-central Massachusetts. Dust samples were collected at the time of home interview in 999 homes as part of an ongoing longitudinal birth cohort study of 1,002 infants and their asthmatic siblings. The analysis employed lower arid upper cut points for group 1 dust mite (greater than or equal to2.0 mug/g and greater than or equal to10 mug/g), cockroach (greater than or equal to1.0 U/g and greater than or equal to4.0 U/g), cat (greater than or equal to1.0 mug/g and greater than or equal to8.0 ug/g), and dog (greater than or equal to2.0 mug/g and 10.0 mug/g) allergens. Subject residences were geocoded to assess population density from the U.S. Census, and multiple logistic regression was used to control for confounding, The portion of homes at the lower cut point for dust mite, cockroach, cat, and dog allergens were 46.9%, 24.9%, 42.2%, and 35.6%, respectively; the upper cut point for each of the allergens was reached in 22.4%, 13.4%, 21.0%, and 22.9% of the homes, respectively. In all, 86.0% of the homes had at least one allergen at the lower cut point, and 58.0% had at least one allergen at the upper cut point. Forty-nine percent of the homes had two or more allergens at the lower cut point, and 19.7% had two or more allergens at the upper cut point. Higher education of the mother, higher household income, living in a single-family home in a less densely populated area with fewer people per room, and being a white household were associated with elevated dust mite, cat, and dog allergens and low cockroach allergen. In contrast, low income, living in a multifamily home in a high population density area with a higher occupancy rate per room, and being a Hispanic or black household were associated with elevated cockroach allergens and low concentrations of dust mite, cat, and dog allergens. Although the presence of an individual allergen is more likely associated with one or more socioeconomic or ethnic factors, most homes typically have multiple allergen burdens in excess of concentrations thought to be associated with sensitization and exacerbation of asthma. Mite and cockroach allergens have distinct and opposite associations with socioeconomic factors and population density.. aeroallergens| asthma| cats| cockroaches| dogs| dust mites| indoor air| socioeconomic factors|inner-city children| monoclonal-antibodies| indoor allergens| puerto-rican| risk-factors| exposure| prevalence| mortality| sensitization| morbidity.	APR-2002	aeroallergens| asthma| cats| cockroaches| dogs| dust mites| indoor air| socioeconomic factors|inner-city children| monoclonal-antibodies| indoor allergens| puerto-rican| risk-factors| exposure| prevalence| mortality| sensitization| morbidity	Leaderer, BP; Belanger, K; Triche, E; Holford, T; Gold, DR; Kim, Y; Jankun, T; Ren, P; McSharry, JE; Plattsmills, TAE; Chapman, MD; Bracken, MB	Dust mite, cockroach, cat, and dog allergen concentrations in homes of asthmatic children in the northeastern United States: Impact of socioeconomic factors and population density		ENVIRONMENTAL HEALTH PERSPECTIVES	aeroallergens; asthma; cats; cockroaches; dogs; dust mites; indoor air; socioeconomic factors	INNER-CITY CHILDREN; MONOCLONAL-ANTIBODIES; INDOOR ALLERGENS; PUERTO-RICAN; RISK-FACTORS; EXPOSURE; PREVALENCE; MORTALITY; SENSITIZATION; MORBIDITY	Home exposures to aeroallergens are an important environmental factor in allergic sensitization and in the development and exacerbation of asthma. We assessed variations in home concentrations of dust Mite, cock-roach, cat, and dog allergens in dust collected in the main living areas of asthmatics' homes by family income, mother's education, dwelling type, population density, household population density, and ethnicity in Connecticut and south-central Massachusetts. Dust samples were collected at the time of home interview in 999 homes as part of an ongoing longitudinal birth cohort study of 1,002 infants and their asthmatic siblings. The analysis employed lower arid upper cut points for group 1 dust mite (greater than or equal to2.0 mug/g and greater than or equal to10 mug/g), cockroach (greater than or equal to1.0 U/g and greater than or equal to4.0 U/g), cat (greater than or equal to1.0 mug/g and greater than or equal to8.0 ug/g), and dog (greater than or equal to2.0 mug/g and 10.0 mug/g) allergens. Subject residences were geocoded to assess population density from the U.S. Census, and multiple logistic regression was used to control for confounding, The portion of homes at the lower cut point for dust mite, cockroach, cat, and dog allergens were 46.9%, 24.9%, 42.2%, and 35.6%, respectively; the upper cut point for each of the allergens was reached in 22.4%, 13.4%, 21.0%, and 22.9% of the homes, respectively. In all, 86.0% of the homes had at least one allergen at the lower cut point, and 58.0% had at least one allergen at the upper cut point. Forty-nine percent of the homes had two or more allergens at the lower cut point, and 19.7% had two or more allergens at the upper cut point. Higher education of the mother, higher household income, living in a single-family home in a less densely populated area with fewer people per room, and being a white household were associated with elevated dust mite, cat, and dog allergens and low cockroach allergen. In contrast, low income, living in a multifamily home in a high population density area with a higher occupancy rate per room, and being a Hispanic or black household were associated with elevated cockroach allergens and low concentrations of dust mite, cat, and dog allergens. Although the presence of an individual allergen is more likely associated with one or more socioeconomic or ethnic factors, most homes typically have multiple allergen burdens in excess of concentrations thought to be associated with sensitization and exacerbation of asthma. Mite and cockroach allergens have distinct and opposite associations with socioeconomic factors and population density.	37	124	2002	7		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Systematic review: Exposure to pets and risk of asthma and asthma-like symptoms. Background: Studies of exposure to pets and risk of asthma have yielded conflicting results. Objectives: We performed a systematic review to synthesize the evidence of the effect of exposure to pets in the home on the risk of asthma and asthma-related symptoms. We also assessed differences between the studies as sources of heterogeneity of the results. Methods: We conducted a MEDLINE search (until the end of 1999) using the following boolean search command: (asthma[all] OR wheez*[all]) AND (domestic animal*[all] OR pets[all]). The outcome was limited to either diagnosis of asthma or the symptom of wheezing, The exposure of interest was domestic animals in the home, Appropriate temporal relationship was defined as present in studies with either pet keeping within the first 2 years of life, in the past, or exposure to pets preceding the outcome. Results: Thirty-two of the 217 retrieved articles fulfilled the eligibility criteria. Inappropriate time sequence of the exposure and outcome information was an important source of heterogeneity and an indication of potential selection bias. Therefore we analyzed studies focusing on early exposure or ensuring appropriate temporal sequence. The pooled risk estimates for both asthma (fixed-effects odds ratio, 1.11; 95% CI, 0.98-1.25; heterogeneity, P = .04; random-effects odds ratio, 1.09; 95% CI, 0.89-1.34) and wheezing (fixed-effects odds ratio, 1.19; 95% CI, 1.05-1.35; heterogeneity, P = .03; random-effects odds ratio, 1.17; 95% CI, 0.95-1.44) indicated a small effect, which was limited to studies with a median study population age of over 6 years (fixed-effects odds ratio, 1.19; 95% CI, 1.02-1.40; heterogeneity, P = .04; random-effects odds ratio, 1.15; 95% CI, 0.86-1.56; fixed-effects odds ratio, 1.29; 95% CI, 1.12-1.48; heterogeneity, P = .31). In younger children the harmful effect disappeared for wheezing (odds ratio, 0.80; 95% CI, 0.59-1.08; P = .38). Conclusion: Exposure to pets appears to increase the risk of asthma and wheezing in older children. The observed lower risk among exposed than among unexposed young children is consistent with a protective effect in this age, group but could also be explained by selection bias.. pets| asthma| wheeze| domestic animal| meta-analysis| selection bias|respiratory symptoms| childhood asthma| home-environment| atopic sensitization| children| prevalence| allergy| cat| association| morbidity.	MAR-2001	pets| asthma| wheeze| domestic animal| meta-analysis| selection bias|respiratory symptoms| childhood asthma| home-environment| atopic sensitization| children| prevalence| allergy| cat| association| morbidity	Apelberg, BJ; Aoki, Y; Jaakkola, JJK	Systematic review: Exposure to pets and risk of asthma and asthma-like symptoms		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	pets; asthma; wheeze; domestic animal; meta-analysis; selection bias	RESPIRATORY SYMPTOMS; CHILDHOOD ASTHMA; HOME-ENVIRONMENT; ATOPIC SENSITIZATION; CHILDREN; PREVALENCE; ALLERGY; CAT; ASSOCIATION; MORBIDITY	Background: Studies of exposure to pets and risk of asthma have yielded conflicting results. Objectives: We performed a systematic review to synthesize the evidence of the effect of exposure to pets in the home on the risk of asthma and asthma-related symptoms. We also assessed differences between the studies as sources of heterogeneity of the results. Methods: We conducted a MEDLINE search (until the end of 1999) using the following boolean search command: (asthma[all] OR wheez*[all]) AND (domestic animal*[all] OR pets[all]). The outcome was limited to either diagnosis of asthma or the symptom of wheezing, The exposure of interest was domestic animals in the home, Appropriate temporal relationship was defined as present in studies with either pet keeping within the first 2 years of life, in the past, or exposure to pets preceding the outcome. Results: Thirty-two of the 217 retrieved articles fulfilled the eligibility criteria. Inappropriate time sequence of the exposure and outcome information was an important source of heterogeneity and an indication of potential selection bias. Therefore we analyzed studies focusing on early exposure or ensuring appropriate temporal sequence. The pooled risk estimates for both asthma (fixed-effects odds ratio, 1.11; 95% CI, 0.98-1.25; heterogeneity, P = .04; random-effects odds ratio, 1.09; 95% CI, 0.89-1.34) and wheezing (fixed-effects odds ratio, 1.19; 95% CI, 1.05-1.35; heterogeneity, P = .03; random-effects odds ratio, 1.17; 95% CI, 0.95-1.44) indicated a small effect, which was limited to studies with a median study population age of over 6 years (fixed-effects odds ratio, 1.19; 95% CI, 1.02-1.40; heterogeneity, P = .04; random-effects odds ratio, 1.15; 95% CI, 0.86-1.56; fixed-effects odds ratio, 1.29; 95% CI, 1.12-1.48; heterogeneity, P = .31). In younger children the harmful effect disappeared for wheezing (odds ratio, 0.80; 95% CI, 0.59-1.08; P = .38). Conclusion: Exposure to pets appears to increase the risk of asthma and wheezing in older children. The observed lower risk among exposed than among unexposed young children is consistent with a protective effect in this age, group but could also be explained by selection bias.	48	124	2001	6	10.1067/mai.2001.113240	Allergy; Immunology
Health effects related to environmental tobacco smoke exposure in children in the United States - Data from the Third National Health and Nutrition Examination Survey. Objective: To determine the effects of prenatal. and postnatal smoke exposure on the respiratory health of children in the United States. Design: Nationally representative cross-sectional survey, including questionnaire information, measurements of serum cotinine (a metabolite of nicotine), and pulmonary function measurement, of 5400 US children. Setting and Participants: Children aged 4 to 16 years in the Third National Health and Nutrition Examination Survey, October 25, 1988, to October 15, 1994. Methods: We stratified the study participants into tertiles, on the basis of serum cotinine levels, and used logistic and linear regression modeling, adjusting for known covariates, to determine the effect of high environmental tobacco smoke (ETS) exposure (on the basis of a high cotinine level) on outcomes such as the prevalence of current asthma, the prevalence of frequent wheezing, school absence, and lung function. For children aged 4 to 11 years, we also determined the effect of prenatal maternal smoking on these outcomes. Results: We observed effects of ETS exposure in all age groups, although the effects varied between age groups. Among all children significant effects associated with high cotinine levels were for wheezing apart from cold in the past year (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.8); 6 or more days of school absence in the past year (OR, 2.0; 95% CI, 1.4-2.8); and lung function decrements in the forced expiratory volume in 1 second (mean change, -1.8%; 95% CI, -3.2% to -0.4%) and the maximal midexpiratory flow (mean change, -5.9%; 95% CI, -8.1% to -3.4%). Although current and ever asthma were not significantly associated with high cotinine levels in the overall group (OR, 1.5; 95% CI, 0.8-2.7, and OR, 1.3; 95% CI, 0.8-2.2, respectively), they were increased significantly among 4- to 6-year-old children (OR, 5.3; 95% CI, 2.2-12.7, and OR, 2.3; 95% CI, 1.1-5.1, respectively). Conclusions: We investigated recent ETS exposures as important predictors of respiratory health outcomes in children 4 years and older. Environmental tobacco smoke exposure affects children of all ages, although the exact effects may vary between age groups.. parental smoking| passive smoking| cotinine| particulate| pollution| workplace| childhood| asthma.	JAN-2001	parental smoking| passive smoking| cotinine| particulate| pollution| workplace| childhood| asthma	Mannino, DM; Moorman, JE; Kingsley, B; Rose, D; Repace, J	Health effects related to environmental tobacco smoke exposure in children in the United States - Data from the Third National Health and Nutrition Examination Survey		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		PARENTAL SMOKING; PASSIVE SMOKING; COTININE; PARTICULATE; POLLUTION; WORKPLACE; CHILDHOOD; ASTHMA	Objective: To determine the effects of prenatal. and postnatal smoke exposure on the respiratory health of children in the United States. Design: Nationally representative cross-sectional survey, including questionnaire information, measurements of serum cotinine (a metabolite of nicotine), and pulmonary function measurement, of 5400 US children. Setting and Participants: Children aged 4 to 16 years in the Third National Health and Nutrition Examination Survey, October 25, 1988, to October 15, 1994. Methods: We stratified the study participants into tertiles, on the basis of serum cotinine levels, and used logistic and linear regression modeling, adjusting for known covariates, to determine the effect of high environmental tobacco smoke (ETS) exposure (on the basis of a high cotinine level) on outcomes such as the prevalence of current asthma, the prevalence of frequent wheezing, school absence, and lung function. For children aged 4 to 11 years, we also determined the effect of prenatal maternal smoking on these outcomes. Results: We observed effects of ETS exposure in all age groups, although the effects varied between age groups. Among all children significant effects associated with high cotinine levels were for wheezing apart from cold in the past year (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.8); 6 or more days of school absence in the past year (OR, 2.0; 95% CI, 1.4-2.8); and lung function decrements in the forced expiratory volume in 1 second (mean change, -1.8%; 95% CI, -3.2% to -0.4%) and the maximal midexpiratory flow (mean change, -5.9%; 95% CI, -8.1% to -3.4%). Although current and ever asthma were not significantly associated with high cotinine levels in the overall group (OR, 1.5; 95% CI, 0.8-2.7, and OR, 1.3; 95% CI, 0.8-2.2, respectively), they were increased significantly among 4- to 6-year-old children (OR, 5.3; 95% CI, 2.2-12.7, and OR, 2.3; 95% CI, 1.1-5.1, respectively). Conclusions: We investigated recent ETS exposures as important predictors of respiratory health outcomes in children 4 years and older. Environmental tobacco smoke exposure affects children of all ages, although the exact effects may vary between age groups.	22	124	2001	6		Pediatrics
Airway eosinophilia is not a requirement for allergen-induced airway hyperresponsiveness. Background House dust mites (HDMs) are the major source of perennial allergens causing human allergic asthma. Animal models mimicking as closely as possible the allergic features observed in human asthma are therefore interesting tools for studying the immunological and pathophysiological mechanisms involved. Especially the role of eosinophils and allergen-specific immunoglobulin (Ig) E in the pathophysiology of airway hyperresponsiveness (AHR) remains a subject of intense debate. Objective To develop a mouse model of allergic airway inflammation and hyperresponsiveness based on the use of purified house dust mite allergen (Der p 1) as clinical relevant allergen. Furthermore, we studied the effects of low dose allergen exposure on the airway eosinophilia and AHR. Methods On day 0, C57B1/6 mice were immunized with purified Der p 1 intraperitoneally. From day 14-20, the mice were exposed daily to a 30-min aerosol of different concentrations of house dust mite extract. Results Mice, actively immunized with Der p 1 and subsequently exposed to HDM aerosols, developed AHR, eosinophil infiltration of the airways and allergen-specific IgE. Moreover, lowering the concentration of the HDM aerosol also induced AHR and IgE without apparent eosinophil influx into the airways. Der p 1-sensitized mice exposed to PBS produced IgE, but did not show AHR or eosinophil influx. Conclusion This in vivo model of HDM-induced allergic airway changes suggests that AHR is not related to either eosinophil influx or allergen-specific serum IgE, thereby reducing the importance of these factors as essential elements for allergic AHR.. airway hyperresponsiveness| der p 1| eosinophil| house dust mite| immunoglobulin e|cell-deficient mice| dust mite allergen| der-p-i| t-cells| dermatophagoides-pteronyssinus| bronchial hyperreactivity| murine model| guinea-pigs| inflammation| asthma.	JAN-2000	airway hyperresponsiveness| der p 1| eosinophil| house dust mite| immunoglobulin e|cell-deficient mice| dust mite allergen| der-p-i| t-cells| dermatophagoides-pteronyssinus| bronchial hyperreactivity| murine model| guinea-pigs| inflammation| asthma	Tournoy, KG; Kips, JC; Schou, C; Pauwels, RA	Airway eosinophilia is not a requirement for allergen-induced airway hyperresponsiveness		CLINICAL AND EXPERIMENTAL ALLERGY	airway hyperresponsiveness; Der p 1; eosinophil; house dust mite; immunoglobulin E	CELL-DEFICIENT MICE; DUST MITE ALLERGEN; DER-P-I; T-CELLS; DERMATOPHAGOIDES-PTERONYSSINUS; BRONCHIAL HYPERREACTIVITY; MURINE MODEL; GUINEA-PIGS; INFLAMMATION; ASTHMA	Background House dust mites (HDMs) are the major source of perennial allergens causing human allergic asthma. Animal models mimicking as closely as possible the allergic features observed in human asthma are therefore interesting tools for studying the immunological and pathophysiological mechanisms involved. Especially the role of eosinophils and allergen-specific immunoglobulin (Ig) E in the pathophysiology of airway hyperresponsiveness (AHR) remains a subject of intense debate. Objective To develop a mouse model of allergic airway inflammation and hyperresponsiveness based on the use of purified house dust mite allergen (Der p 1) as clinical relevant allergen. Furthermore, we studied the effects of low dose allergen exposure on the airway eosinophilia and AHR. Methods On day 0, C57B1/6 mice were immunized with purified Der p 1 intraperitoneally. From day 14-20, the mice were exposed daily to a 30-min aerosol of different concentrations of house dust mite extract. Results Mice, actively immunized with Der p 1 and subsequently exposed to HDM aerosols, developed AHR, eosinophil infiltration of the airways and allergen-specific IgE. Moreover, lowering the concentration of the HDM aerosol also induced AHR and IgE without apparent eosinophil influx into the airways. Der p 1-sensitized mice exposed to PBS produced IgE, but did not show AHR or eosinophil influx. Conclusion This in vivo model of HDM-induced allergic airway changes suggests that AHR is not related to either eosinophil influx or allergen-specific serum IgE, thereby reducing the importance of these factors as essential elements for allergic AHR.	38	124	2000	7		Allergy; Immunology
The role of dendritic and epithelial cells as master regulators of allergic airway inflammation. Lung dendritic cells bridge innate and adaptive immunity, integrating a variety of stimuli from allergens, microbial colonisation, environmental pollution, and innate immune cells into a signal for T lymphocytes of the adaptive immune system. Dendritic cells have a pivotal role in the activation of T helper (Th) 2 cells and allergic inflammation. Lung dendritic cells can also prevent harmful immune responses to innocuous inhaled antigens via induction of regulatory T cells or Th1 cells. In our Review, we discuss how understanding the biology of dendritic cells is crucial for understanding the interaction between allergens, the environment, and genetics, and focus on how dendritic cells conspire with airway epithelial cells and innate pro-Th2 cells to cause allergic sensitisation and asthma.. house-dust mite| thymic stromal lymphopoietin| respiratory syncytial virus| cd4(+) t-cells| immune-responses| inhaled antigen| cigarette-smoke| lymph-nodes| in-vivo| experimental asthma.	SEP 4-2010	house-dust mite| thymic stromal lymphopoietin| respiratory syncytial virus| cd4(+) t-cells| immune-responses| inhaled antigen| cigarette-smoke| lymph-nodes| in-vivo| experimental asthma	Lambrecht, BN; Hammad, H	The role of dendritic and epithelial cells as master regulators of allergic airway inflammation		LANCET		HOUSE-DUST MITE; THYMIC STROMAL LYMPHOPOIETIN; RESPIRATORY SYNCYTIAL VIRUS; CD4(+) T-CELLS; IMMUNE-RESPONSES; INHALED ANTIGEN; CIGARETTE-SMOKE; LYMPH-NODES; IN-VIVO; EXPERIMENTAL ASTHMA	Lung dendritic cells bridge innate and adaptive immunity, integrating a variety of stimuli from allergens, microbial colonisation, environmental pollution, and innate immune cells into a signal for T lymphocytes of the adaptive immune system. Dendritic cells have a pivotal role in the activation of T helper (Th) 2 cells and allergic inflammation. Lung dendritic cells can also prevent harmful immune responses to innocuous inhaled antigens via induction of regulatory T cells or Th1 cells. In our Review, we discuss how understanding the biology of dendritic cells is crucial for understanding the interaction between allergens, the environment, and genetics, and focus on how dendritic cells conspire with airway epithelial cells and innate pro-Th2 cells to cause allergic sensitisation and asthma.	95	123	2010	9	10.1016/S0140-6736(10)61226-3	General & Internal Medicine
Standard skin prick testing and sensitization to inhalant allergens across Europe - a survey from the GA(2)LEN network. Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal > 3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.. european network| inhalant allergens| standard skin prick testing|respiratory-health-survey| bronchial hyperresponsiveness| individual allergens| copenhagen allergy| common allergens| school-children| test reactivity| atopic eczema| young-adults| hay-fever.	OCT-2005	european network| inhalant allergens| standard skin prick testing|respiratory-health-survey| bronchial hyperresponsiveness| individual allergens| copenhagen allergy| common allergens| school-children| test reactivity| atopic eczema| young-adults| hay-fever	Heinzerling, L; Frew, AJ; Bindslev-Jensen, C; Bonini, S; Bousquet, J; Bresciani, M; Carlsen, KH; Cauwenberge, P; Darsow, U; Fokkens, WJ; Haahtela, T; van Hoecke, H; Jessberger, B; Kowalski, ML; Kopp, T; Lahoz, CN; Lodrup Carlsen, KC; Papadopoulos, NG; Ring, J; Schmid-Grendelmeier, P; Vignola, AM; Wohrl, S; Zuberbier, T	Standard skin prick testing and sensitization to inhalant allergens across Europe - a survey from the GA(2)LEN network		ALLERGY	European network; inhalant allergens; standard skin prick testing	RESPIRATORY-HEALTH-SURVEY; BRONCHIAL HYPERRESPONSIVENESS; INDIVIDUAL ALLERGENS; COPENHAGEN ALLERGY; COMMON ALLERGENS; SCHOOL-CHILDREN; TEST REACTIVITY; ATOPIC ECZEMA; YOUNG-ADULTS; HAY-FEVER	Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal > 3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel.	49	123	2005	14	10.1111/j.1398-9995.2005.00895.x	Allergy; Immunology
Pulmonary effects of indoor- and outdoor-generated particles in children with asthma. Most particulate matter (PM) health effects studies use outdoor (ambient) PM as a surrogate for personal exposure. However, people spend most of their time indoors exposed to a combination of indoor-generated particles and ambient particles that have infiltrated. Thus, it is important to investigate the differential health effects of indoor- and ambient-generated particles. We combined our recently adapted recursive model and a predictive model for estimating infiltration efficiency to separate personal exposure (L) to PM2.5 (PM with aerodynamic diameter <= 2.5 pm) into its indoor-generated (E-ig) and ambient-generated (E-ag) components for 19 children with asthma. We then compared E-ig and E-ag to changes in exhaled nitric oxide (eNO), a marker of airway inflammation. Based on the recursive model with a sample size of eight children, E-ag was marginally associated with increases in eNO [5.6 ppb per 10-mu g/m(3) increase in PM2.5; 95% confidence interval (CI), -0.6 to 11.9; p = 0.08]. E-ig was not associated with eNO (-0.19 ppb change per 10 mu g/m(3)). Our predictive model allowed us to estimate E-ag and E-ig for all 19 children. For those combined estimates, only E-ag was significantly associated with an increase in eNO (E-ag: 5.0 ppb per 10-mu g/m(3) increase in PM2.5; 95% CI, 0.3 to 9.7; p = 0.04; E-ig: 3.3 ppb per 10-mu g/m(3) increase in PM2.5; 95% CI, -1.1 to 7.7; p = 0.15). Effects were seen only in children who were not using corticosteroid therapy. We conclude that the ambient-generated component of PM2.5 exposure is consistently associated with increases in eNO, and the indoor-generated component is less strongly associated with eNO.. ambient air pollution| asthma| exhaled nitric oxide| infiltration| pm2.5|exhaled nitric-oxide| antiinflammatory medication use| particulate air-pollution| hospital admissions| respiratory symptoms| lung-function| association| exposure| matter| seattle.	APR-2005	ambient air pollution| asthma| exhaled nitric oxide| infiltration| pm2.5|exhaled nitric-oxide| antiinflammatory medication use| particulate air-pollution| hospital admissions| respiratory symptoms| lung-function| association| exposure| matter| seattle	Koenig, JQ; Mar, TF; Allen, RW; Jansen, K; Lumley, T; Sullivan, JH; Trenga, CA; Larson, TV; Liu, LJS	Pulmonary effects of indoor- and outdoor-generated particles in children with asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	ambient air pollution; asthma; exhaled nitric oxide; infiltration; PM2.5	EXHALED NITRIC-OXIDE; ANTIINFLAMMATORY MEDICATION USE; PARTICULATE AIR-POLLUTION; HOSPITAL ADMISSIONS; RESPIRATORY SYMPTOMS; LUNG-FUNCTION; ASSOCIATION; EXPOSURE; MATTER; SEATTLE	Most particulate matter (PM) health effects studies use outdoor (ambient) PM as a surrogate for personal exposure. However, people spend most of their time indoors exposed to a combination of indoor-generated particles and ambient particles that have infiltrated. Thus, it is important to investigate the differential health effects of indoor- and ambient-generated particles. We combined our recently adapted recursive model and a predictive model for estimating infiltration efficiency to separate personal exposure (L) to PM2.5 (PM with aerodynamic diameter <= 2.5 pm) into its indoor-generated (E-ig) and ambient-generated (E-ag) components for 19 children with asthma. We then compared E-ig and E-ag to changes in exhaled nitric oxide (eNO), a marker of airway inflammation. Based on the recursive model with a sample size of eight children, E-ag was marginally associated with increases in eNO [5.6 ppb per 10-mu g/m(3) increase in PM2.5; 95% confidence interval (CI), -0.6 to 11.9; p = 0.08]. E-ig was not associated with eNO (-0.19 ppb change per 10 mu g/m(3)). Our predictive model allowed us to estimate E-ag and E-ig for all 19 children. For those combined estimates, only E-ag was significantly associated with an increase in eNO (E-ag: 5.0 ppb per 10-mu g/m(3) increase in PM2.5; 95% CI, 0.3 to 9.7; p = 0.04; E-ig: 3.3 ppb per 10-mu g/m(3) increase in PM2.5; 95% CI, -1.1 to 7.7; p = 0.15). Effects were seen only in children who were not using corticosteroid therapy. We conclude that the ambient-generated component of PM2.5 exposure is consistently associated with increases in eNO, and the indoor-generated component is less strongly associated with eNO.	39	123	2005	5	10.1289/ehp.7511	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Management of hypersensitivity reactions to iodinated contrast media. All iodinated contrast media (CM) are known to cause both immediate (less than or equal to1 h) and nonimmediate (>1 h) hypersensitivity reactions. Although for most immediate reactions an allergic hypersensitivity cannot be demonstrated, recent studies indicate that the severe immediate reactions may be IgE-mediated, while most of the nonimmediate exanthematous skin reactions, appear to be T-cell mediated. Patients who experience such hypersensitivity reactions are therefore advised to undergo an allergologic evaluation. Several investigators have found skin testing to be useful in confirming a CM allergy, especially in patients with nonimmediate skin eruptions. If a patient with confirmed allergy to a CM needs a new CM exposure, a skin test negative CM should be chosen and premedication may be tried. However, none of these precautional measures is a guarantee against a repeat reaction. More research focusing on pathomechanisms, diagnostic testing and premedication is therefore clearly needed in order to prevent CM-induced hypersensitivity reactions in the future.. contrast media| diagnosis| immediate reaction| nonimmediate reaction| premedication| skin tests|delayed adverse-reactions| late-type allergy| anaphylactoid reaction| radiocontrast medium| invitro histamine| drug-reactions| skin-tests| agents| premedication| frequency.	FEB-2005	contrast media| diagnosis| immediate reaction| nonimmediate reaction| premedication| skin tests|delayed adverse-reactions| late-type allergy| anaphylactoid reaction| radiocontrast medium| invitro histamine| drug-reactions| skin-tests| agents| premedication| frequency	Brockow, K; Christiansen, C; Kanny, G; Clement, O; Barbaud, A; Bircher, A; DeWachter, P; Gueant, JL; Gueant, RMR; Mouton-Faivre, C; Ring, J; Romano, A; Sainte-Laudy, J; Demoly, P; Pichler, WJ	Management of hypersensitivity reactions to iodinated contrast media		ALLERGY	contrast media; diagnosis; immediate reaction; nonimmediate reaction; premedication; skin tests	DELAYED ADVERSE-REACTIONS; LATE-TYPE ALLERGY; ANAPHYLACTOID REACTION; RADIOCONTRAST MEDIUM; INVITRO HISTAMINE; DRUG-REACTIONS; SKIN-TESTS; AGENTS; PREMEDICATION; FREQUENCY	All iodinated contrast media (CM) are known to cause both immediate (less than or equal to1 h) and nonimmediate (>1 h) hypersensitivity reactions. Although for most immediate reactions an allergic hypersensitivity cannot be demonstrated, recent studies indicate that the severe immediate reactions may be IgE-mediated, while most of the nonimmediate exanthematous skin reactions, appear to be T-cell mediated. Patients who experience such hypersensitivity reactions are therefore advised to undergo an allergologic evaluation. Several investigators have found skin testing to be useful in confirming a CM allergy, especially in patients with nonimmediate skin eruptions. If a patient with confirmed allergy to a CM needs a new CM exposure, a skin test negative CM should be chosen and premedication may be tried. However, none of these precautional measures is a guarantee against a repeat reaction. More research focusing on pathomechanisms, diagnostic testing and premedication is therefore clearly needed in order to prevent CM-induced hypersensitivity reactions in the future.	80	123	2005	9	10.1111/j.1398-9995.2005.00745.x	Allergy; Immunology
Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life. Daycare attendance and siblings are associated with viral-induced wheezing in children. Preexisting immunologic factors may influence the expression of viral infections in infancy, and in turn, recurrent infections may influence the development of immune responses. A total of 285 children were enrolled in the Childhood Origins of Asthma Project at birth and followed for at least 1 year. Cord blood and 1-year mononuclear cells were stimulated with phytohemagglutinin, and cytokine-response profiles were measured by enzyme-linked immunosorbent assay. Nasal lavage was performed for moderate to severe respiratory illnesses. Daycare attendance and/or siblings significantly increased the likelihood of contracting respiratory syncytial virus (1.5-1.6-fold increase) and rhinovirus (1.8-2.1-fold increase), and increased the risk of rhinovirus-induced wheezing (14-18% vs. 2%, p = 0.011). Cord blood IFN-gamma responses were inversely related to the frequency of viral respiratory infections (r(s) = -0.11, p = 0.05), and more significant for subjects with high exposure to other children (r(s) = -0.27, p = 0.028). The interval change in infantile IFN-gamma responses correlated positively with the frequency of viral infections in infancy (r(s) = 0.12, p = 0.047). These data suggest that neonatal IFN-gamma responses may influence antiviral activity, or may represent a marker of antiviral immunity maturation. Conversely, the frequency of viral infections in infancy can influence IFN-gamma responses.. interferon-gamma| respiratory syncytial virus| daycare| sibling|day-care attendance| interferon-gamma| syncytial virus| airway inflammation| tract illness| asthma| children| rats| bronchiolitis| infancy.	JUL 15-2004	interferon-gamma| respiratory syncytial virus| daycare| sibling|day-care attendance| interferon-gamma| syncytial virus| airway inflammation| tract illness| asthma| children| rats| bronchiolitis| infancy	Copenhaver, CC; Gern, JE; Li, ZH; Shult, PA; Rosenthal, LA; Mikus, LD; Kirk, CJ; Roberg, KA; Anderson, EL; Tisler, CJ; DaSilva, DF; Hiemke, HJ; Gentile, K; Gangnon, RE; Lemanske, RF	Cytokine response patterns, exposure to viruses, and respiratory infections in the first year of life		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	interferon-gamma; respiratory syncytial virus; daycare; sibling	DAY-CARE ATTENDANCE; INTERFERON-GAMMA; SYNCYTIAL VIRUS; AIRWAY INFLAMMATION; TRACT ILLNESS; ASTHMA; CHILDREN; RATS; BRONCHIOLITIS; INFANCY	Daycare attendance and siblings are associated with viral-induced wheezing in children. Preexisting immunologic factors may influence the expression of viral infections in infancy, and in turn, recurrent infections may influence the development of immune responses. A total of 285 children were enrolled in the Childhood Origins of Asthma Project at birth and followed for at least 1 year. Cord blood and 1-year mononuclear cells were stimulated with phytohemagglutinin, and cytokine-response profiles were measured by enzyme-linked immunosorbent assay. Nasal lavage was performed for moderate to severe respiratory illnesses. Daycare attendance and/or siblings significantly increased the likelihood of contracting respiratory syncytial virus (1.5-1.6-fold increase) and rhinovirus (1.8-2.1-fold increase), and increased the risk of rhinovirus-induced wheezing (14-18% vs. 2%, p = 0.011). Cord blood IFN-gamma responses were inversely related to the frequency of viral respiratory infections (r(s) = -0.11, p = 0.05), and more significant for subjects with high exposure to other children (r(s) = -0.27, p = 0.028). The interval change in infantile IFN-gamma responses correlated positively with the frequency of viral infections in infancy (r(s) = 0.12, p = 0.047). These data suggest that neonatal IFN-gamma responses may influence antiviral activity, or may represent a marker of antiviral immunity maturation. Conversely, the frequency of viral infections in infancy can influence IFN-gamma responses.	29	123	2004	6	10.1164/rccm.200312-1647OC	General & Internal Medicine; Respiratory System
Parameters associated with persistent airflow obstruction in chronic severe asthma. The significance of severe airflow obstruction in severe asthma is unclear. The current study determined whether severe airflow obstruction is related to inflammatory or structural changes in the airways. Patients with severe asthma from a tertiary referral clinic were divided into two groups according to their postbronchodilator forced expiratory volume in one second (FEV1): severe persistent airflow limitation (FEV1 <50% predicted; group S; n=37) and no obstruction (FEV1 >80% pred; group N; n=29). Smoking history, atopic status, lung function tests, exhaled NO, blood eosinophil count, quality of life scores using St George's Respiratory Questionnaire and high resolution computed tomography (HRCT) of the lungs were assessed. Patients from group S were older and had longer disease duration. There was no difference in smoking history, atopic status, hospital admissions, quality of life scores and amount of treatment with inhaled or oral corticosteroids. Exhaled NO and peripheral blood eosinophils were higher in group S (21.0+/-2.4 versus 12.8+/-2.3 ppb; 0.41+/-0.06 versus 0.15+/-0.03x10(9)cells(.)L(-1), respectively). HRCT scores for bronchial wall thickening and dilatation were higher in group S with no differences in air trapping. Peripheral blood eosinophilia and bronchial wall thickening on HRCT scan were the only parameters significantly and independently associated with persistent airflow obstruction. Patients with severe asthma and irreversible airflow obstruction had longer disease duration, a greater inflammatory process and more high resolution computed tomography airway abnormalities suggestive of airway remodelling, despite being on similar treatments and experiencing equivalent impairment in quality of life.. airway remodelling| airway thickening| eosinophils| severe asthma|quality-of-life| resolution computed-tomography| health-status| inhaled budesonide| disease severity| wall thickness| nitric-oxide| mild asthma| inflammation| lungs.	JUL-2004	airway remodelling| airway thickening| eosinophils| severe asthma|quality-of-life| resolution computed-tomography| health-status| inhaled budesonide| disease severity| wall thickness| nitric-oxide| mild asthma| inflammation| lungs	Bumbacea, D; Campbell, D; Nguyen, L; Carr, D; Barnes, PJ; Robinson, D; Chung, KF	Parameters associated with persistent airflow obstruction in chronic severe asthma		EUROPEAN RESPIRATORY JOURNAL	airway remodelling; airway thickening; eosinophils; severe asthma	QUALITY-OF-LIFE; RESOLUTION COMPUTED-TOMOGRAPHY; HEALTH-STATUS; INHALED BUDESONIDE; DISEASE SEVERITY; WALL THICKNESS; NITRIC-OXIDE; MILD ASTHMA; INFLAMMATION; LUNGS	The significance of severe airflow obstruction in severe asthma is unclear. The current study determined whether severe airflow obstruction is related to inflammatory or structural changes in the airways. Patients with severe asthma from a tertiary referral clinic were divided into two groups according to their postbronchodilator forced expiratory volume in one second (FEV1): severe persistent airflow limitation (FEV1 <50% predicted; group S; n=37) and no obstruction (FEV1 >80% pred; group N; n=29). Smoking history, atopic status, lung function tests, exhaled NO, blood eosinophil count, quality of life scores using St George's Respiratory Questionnaire and high resolution computed tomography (HRCT) of the lungs were assessed. Patients from group S were older and had longer disease duration. There was no difference in smoking history, atopic status, hospital admissions, quality of life scores and amount of treatment with inhaled or oral corticosteroids. Exhaled NO and peripheral blood eosinophils were higher in group S (21.0+/-2.4 versus 12.8+/-2.3 ppb; 0.41+/-0.06 versus 0.15+/-0.03x10(9)cells(.)L(-1), respectively). HRCT scores for bronchial wall thickening and dilatation were higher in group S with no differences in air trapping. Peripheral blood eosinophilia and bronchial wall thickening on HRCT scan were the only parameters significantly and independently associated with persistent airflow obstruction. Patients with severe asthma and irreversible airflow obstruction had longer disease duration, a greater inflammatory process and more high resolution computed tomography airway abnormalities suggestive of airway remodelling, despite being on similar treatments and experiencing equivalent impairment in quality of life.	35	123	2004	7	10.1183/09031936.04.00077803	Respiratory System
Mouse model of airway remodeling - Strain differences. We found that continuous eosinophilic inflammation after repeated antigen instillation into the nose was observed only in A/J mice, not in three other strains. Histologic analysis of tissues from A/J mice revealed features typical of airway remodeling, i.e., airway wall thickening and increased Collagen depositions were observed after 12 weeks' antigen exposure. Persistent airway hyperresponsiveness (AHR) was observed in chronically antigen-exposed A/J mice. Eosinophilic inflammation, Collagen deposition, and airway wall thickening were all less marked in BALB/c mice than in A/J mice, and no AHR was observed in the former strain. In C57BL/6 and C3H/HeJ mice, eosinophilic inflammation, airway wall thickening, and AHR were not observed at all, although slightly increase Collagen deposition was observed. Thus, we found that these changes were strain-dependent. On the other hand, in A/J mice inhalational antigen challenge after ovalbumin/alum immunization led only to a transient increase in eosinophils and to less airway wall thickening, indicating the importance of the protocol used. Use of A/J mice and giving antigen by instillation via the nose is to be recommended for studies of the mechanisms underlying asthma. In particular, useful qualitative and quantitative information relating to the structural and histologic changes in the lungs may be obtainable using this model.. asthma| eosinophil| airway hyperresponsiveness| a/j mouse|smooth-muscle| chronic exposure| murine model| fatal asthma| inbred mice| inflammation| hyperresponsiveness| epithelium| antigen| responsiveness.	OCT 15-2003	asthma| eosinophil| airway hyperresponsiveness| a/j mouse|smooth-muscle| chronic exposure| murine model| fatal asthma| inbred mice| inflammation| hyperresponsiveness| epithelium| antigen| responsiveness	Shinagawa, K; Kojima, M	Mouse model of airway remodeling - Strain differences		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; eosinophil; airway hyperresponsiveness; A/J mouse	SMOOTH-MUSCLE; CHRONIC EXPOSURE; MURINE MODEL; FATAL ASTHMA; INBRED MICE; INFLAMMATION; HYPERRESPONSIVENESS; EPITHELIUM; ANTIGEN; RESPONSIVENESS	We found that continuous eosinophilic inflammation after repeated antigen instillation into the nose was observed only in A/J mice, not in three other strains. Histologic analysis of tissues from A/J mice revealed features typical of airway remodeling, i.e., airway wall thickening and increased Collagen depositions were observed after 12 weeks' antigen exposure. Persistent airway hyperresponsiveness (AHR) was observed in chronically antigen-exposed A/J mice. Eosinophilic inflammation, Collagen deposition, and airway wall thickening were all less marked in BALB/c mice than in A/J mice, and no AHR was observed in the former strain. In C57BL/6 and C3H/HeJ mice, eosinophilic inflammation, airway wall thickening, and AHR were not observed at all, although slightly increase Collagen deposition was observed. Thus, we found that these changes were strain-dependent. On the other hand, in A/J mice inhalational antigen challenge after ovalbumin/alum immunization led only to a transient increase in eosinophils and to less airway wall thickening, indicating the importance of the protocol used. Use of A/J mice and giving antigen by instillation via the nose is to be recommended for studies of the mechanisms underlying asthma. In particular, useful qualitative and quantitative information relating to the structural and histologic changes in the lungs may be obtainable using this model.	39	123	2003	9	10.1164/rccm.200210-1188OC	General & Internal Medicine; Respiratory System
Allergen microarray: comparison of microarray using recombinant allergens with conventional diagnostic methods to detect allergen-specific serum immunoglobulin E. Background The availability of recombinant allergens and recent advances in biochip technology led to the development of a novel test system for the detection of allergen-specific IgE. Objective To test the performance of this allergen microarray in a serological analytical study. Methods Standard allergens contained in grass pollen (Phl p 1, Phl p 2, Phl p 5 and Phl p 6) and tree pollen ( Bet v 1 and Bet v 2) were used as a model system. The detection of allergen-specific serum IgE using microarrays was compared with standard test systems: CAP/RAST and an in-house ELISA. In order to test the analytical sensitivity of the assays, geometric dilutions of a serum pool containing high levels of pollen-specific IgE from allergic individuals were tested in each system. To assess the analytical specificity, the sera of 51 patients with presumptive allergic symptoms were collected before diagnosis. Thereafter, the results for grass/tree-pollen-specific IgE were compared. Results The microarray has a good dynamic range similar to the CAP/RAST system. Microarray and ELISA showed comparable analytical sensitivity exceeding the CAP/RAST system. With respect to the analytical specificity, no significant cross-reactivity of the allergens was observed. For two of the allergens tested, weak positive signals were detected in the microarray test system, whereas they were not detectable by CAP/ RAST. Conclusion A good correlation of presently used methods to detect serum IgE and the novel microarray test system was observed. As a next step, a careful validation of this method for a multitude of allergens and a thorough clinical evaluation has to be provided. Microarray testing of allergen-specific IgE can be presumed to be the method of choice for a prospective component-resolved diagnosis of Type I allergy, and the basis for the design and monitoring of a patient-tailored specific immunotherapy in the future.. ige| microarray technology| recombinant allergen| type i allergy|grass phleum-pratense| pollen allergen| major allergen| protein microarrays| ige| immunoassays| diseases| therapy| cloning| gene.	OCT-2003	ige| microarray technology| recombinant allergen| type i allergy|grass phleum-pratense| pollen allergen| major allergen| protein microarrays| ige| immunoassays| diseases| therapy| cloning| gene	Jahn-Schmid, B; Harwanegg, C; Hiller, R; Bohle, B; Ebner, C; Scheiner, O; Mueller, MW	Allergen microarray: comparison of microarray using recombinant allergens with conventional diagnostic methods to detect allergen-specific serum immunoglobulin E		CLINICAL AND EXPERIMENTAL ALLERGY	IgE; microarray technology; recombinant allergen; Type I allergy	GRASS PHLEUM-PRATENSE; POLLEN ALLERGEN; MAJOR ALLERGEN; PROTEIN MICROARRAYS; IGE; IMMUNOASSAYS; DISEASES; THERAPY; CLONING; GENE	Background The availability of recombinant allergens and recent advances in biochip technology led to the development of a novel test system for the detection of allergen-specific IgE. Objective To test the performance of this allergen microarray in a serological analytical study. Methods Standard allergens contained in grass pollen (Phl p 1, Phl p 2, Phl p 5 and Phl p 6) and tree pollen ( Bet v 1 and Bet v 2) were used as a model system. The detection of allergen-specific serum IgE using microarrays was compared with standard test systems: CAP/RAST and an in-house ELISA. In order to test the analytical sensitivity of the assays, geometric dilutions of a serum pool containing high levels of pollen-specific IgE from allergic individuals were tested in each system. To assess the analytical specificity, the sera of 51 patients with presumptive allergic symptoms were collected before diagnosis. Thereafter, the results for grass/tree-pollen-specific IgE were compared. Results The microarray has a good dynamic range similar to the CAP/RAST system. Microarray and ELISA showed comparable analytical sensitivity exceeding the CAP/RAST system. With respect to the analytical specificity, no significant cross-reactivity of the allergens was observed. For two of the allergens tested, weak positive signals were detected in the microarray test system, whereas they were not detectable by CAP/ RAST. Conclusion A good correlation of presently used methods to detect serum IgE and the novel microarray test system was observed. As a next step, a careful validation of this method for a multitude of allergens and a thorough clinical evaluation has to be provided. Microarray testing of allergen-specific IgE can be presumed to be the method of choice for a prospective component-resolved diagnosis of Type I allergy, and the basis for the design and monitoring of a patient-tailored specific immunotherapy in the future.	27	123	2003	7	10.1046/j.1365-2222.2003.01784.x	Allergy; Immunology
Breast feeding and allergic diseases in infants - a prospective birth cohort study. Aims: To investigate the effect of breast feeding on allergic disease in infants up to 2 years of age. Methods: A birth cohort of 4089 infants was followed prospectively in Stockholm, Sweden. Information about various exposures was obtained by parental questionnaires when the infants were 2 months old, and about allergic symptoms and feeding at 1 and 2 years of age. Duration of exclusive and partial breast feeding was assessed separately. Symptom related definitions of various allergic diseases were used. Odds ratios (OR) and 95% confidence intervals (CI) were estimated in a multiple logistic regression model. Adjustments were made for potential confounders. Results: Children exclusively breast fed during four months or more exhibited less asthma (7.7% v 12%, ORadj 0.7, 95% CI 0.5 to 0.8), less atopic dermatitis (24% v 27%, ORadj = 0.8, 95% CI 0.7 to 1.0), and less suspected allergic rhinitis (6.5% v 9%, ORadj = 0.7, 95% CI 0.5 to 1.0) by 2 years of age. There was a significant risk reduction for asthma related to partial breast feeding during six months or more (ORadj = 0.7, 95% CI 0.5 to 0.9). Three or more of five possible allergic disorders-asthma, suspected allergic rhinitis, atopic dermatitis, food allergy related symptoms, and suspected allergic respiratory symptoms after exposure to pets or pollen-were found in 6.5% of the children. Exclusive breast feeding prevented children from having multiple allergic disease (ORadj = 0.7, 95% CI 0.5 to 0.9) during the first two years of life. Conclusion: Exclusive breast feeding seems to have a preventive effect on the early development of allergic disease-that is, asthma, atopic dermatitis, and suspected allergic rhinitis, up to 2 years of age. This protective effect was also evident for multiple allergic disease.. age 6| asthma| children| childhood| exposure| sensitization| predictors| risk| old.	DEC-2002	age 6| asthma| children| childhood| exposure| sensitization| predictors| risk| old	Kull, I; Wickman, M; Lilja, G; Nordvall, SL; Pershagen, G	Breast feeding and allergic diseases in infants - a prospective birth cohort study		ARCHIVES OF DISEASE IN CHILDHOOD		AGE 6; ASTHMA; CHILDREN; CHILDHOOD; EXPOSURE; SENSITIZATION; PREDICTORS; RISK; OLD	Aims: To investigate the effect of breast feeding on allergic disease in infants up to 2 years of age. Methods: A birth cohort of 4089 infants was followed prospectively in Stockholm, Sweden. Information about various exposures was obtained by parental questionnaires when the infants were 2 months old, and about allergic symptoms and feeding at 1 and 2 years of age. Duration of exclusive and partial breast feeding was assessed separately. Symptom related definitions of various allergic diseases were used. Odds ratios (OR) and 95% confidence intervals (CI) were estimated in a multiple logistic regression model. Adjustments were made for potential confounders. Results: Children exclusively breast fed during four months or more exhibited less asthma (7.7% v 12%, ORadj 0.7, 95% CI 0.5 to 0.8), less atopic dermatitis (24% v 27%, ORadj = 0.8, 95% CI 0.7 to 1.0), and less suspected allergic rhinitis (6.5% v 9%, ORadj = 0.7, 95% CI 0.5 to 1.0) by 2 years of age. There was a significant risk reduction for asthma related to partial breast feeding during six months or more (ORadj = 0.7, 95% CI 0.5 to 0.9). Three or more of five possible allergic disorders-asthma, suspected allergic rhinitis, atopic dermatitis, food allergy related symptoms, and suspected allergic respiratory symptoms after exposure to pets or pollen-were found in 6.5% of the children. Exclusive breast feeding prevented children from having multiple allergic disease (ORadj = 0.7, 95% CI 0.5 to 0.9) during the first two years of life. Conclusion: Exclusive breast feeding seems to have a preventive effect on the early development of allergic disease-that is, asthma, atopic dermatitis, and suspected allergic rhinitis, up to 2 years of age. This protective effect was also evident for multiple allergic disease.	26	123	2002	4	10.1136/adc.87.6.478	Pediatrics
Lactic acid bacteria inhibit T(H)2 cytokine production by mononuclear cells from allergic patients. Background: Among factors potentially involved in the increased prevalence of allergic diseases, modification of the intestinal bacteria flora or lack of bacterial stimulation during childhood has been proposed. Lactic acid bacteria (LAB) present in fermented foods or belonging to the natural intestinal microflora were shown to exert beneficial effects on human health. Recent reports have indicated their capacity to reduce allergic symptoms. Objective: The purpose of this investigation was to determine the effect of LAB on the production of type 2 cytokines, which characterize allergic diseases. Methods: PBMCs from patients allergic to house dust mite versus those from healthy donors were stimulated for 48 hours with the related Dermatophagoides pteronyssinus allergen or with a staphylococcal superantigen. The effect of LAB preincubation was assessed by measuring the type 2 cytokine production by means of specific ELISA. Results: The tested gram-positive LAB were shown to inhibit the secretion of T(H)2 cytokines (IL-4 and IL-5). This effect was dose dependent and was observed irrespective of the LAB strain used. No significant inhibition was induced by the control, gram-negative Escherichia coli TG1. Interestingly, LAB reduced the T(H)2 cytokine production from allergic PBMCs specifically restimulated with the related allergen. The inhibition mechanism was shown to be dependent on antigen-presenting cells (ie, monocytes) and on the involvement of IL-12 and IFN-gamma. Conclusion: The tested LAB strains were demonstrated to exhibit an anti-T(H)2 activity, and thus different, strains of this family might be useful in the prevention of allergic diseases.. allergy| type 2 cytokine| lactic acid bacteria| immunomodulation| superantigen| dust mite|interleukin-12 il-12| probiotics| lactobacilli| childhood| responses| mice.	OCT-2002	allergy| type 2 cytokine| lactic acid bacteria| immunomodulation| superantigen| dust mite|interleukin-12 il-12| probiotics| lactobacilli| childhood| responses| mice	Pochard, P; Gosset, P; Grangette, C; Andre, C; Tonnel, AB; Pestel, J; Mercenier, A	Lactic acid bacteria inhibit T(H)2 cytokine production by mononuclear cells from allergic patients		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; type 2 cytokine; lactic acid bacteria; immunomodulation; superantigen; dust mite	INTERLEUKIN-12 IL-12; PROBIOTICS; LACTOBACILLI; CHILDHOOD; RESPONSES; MICE	Background: Among factors potentially involved in the increased prevalence of allergic diseases, modification of the intestinal bacteria flora or lack of bacterial stimulation during childhood has been proposed. Lactic acid bacteria (LAB) present in fermented foods or belonging to the natural intestinal microflora were shown to exert beneficial effects on human health. Recent reports have indicated their capacity to reduce allergic symptoms. Objective: The purpose of this investigation was to determine the effect of LAB on the production of type 2 cytokines, which characterize allergic diseases. Methods: PBMCs from patients allergic to house dust mite versus those from healthy donors were stimulated for 48 hours with the related Dermatophagoides pteronyssinus allergen or with a staphylococcal superantigen. The effect of LAB preincubation was assessed by measuring the type 2 cytokine production by means of specific ELISA. Results: The tested gram-positive LAB were shown to inhibit the secretion of T(H)2 cytokines (IL-4 and IL-5). This effect was dose dependent and was observed irrespective of the LAB strain used. No significant inhibition was induced by the control, gram-negative Escherichia coli TG1. Interestingly, LAB reduced the T(H)2 cytokine production from allergic PBMCs specifically restimulated with the related allergen. The inhibition mechanism was shown to be dependent on antigen-presenting cells (ie, monocytes) and on the involvement of IL-12 and IFN-gamma. Conclusion: The tested LAB strains were demonstrated to exhibit an anti-T(H)2 activity, and thus different, strains of this family might be useful in the prevention of allergic diseases.	27	123	2002	7	10.1067/mai.2002.128528	Allergy; Immunology
Early life risk factors for adult asthma: A birth cohort study of subjects at risk. Background: Prediction of adult asthma is important, and early prevention strategies should be targeted at those most at risk. Identifying high-risk children at an early age, however, is currently difficult. Objective: We sought to determine those factors present in early life that predict an increased risk of adult asthma. Methods: A prospective cohort study of subjects at risk of asthma and atopy was undertaken in Poole, England. One hundred babies of atopic parents were recruited at birth. During the first 5 years of life, subjects were recalled annually, all respiratory events were reported, and skin prick tests and total serum IgE measurements were performed. At 11 and 22 years, bronchial hyperresponsiveness was also measured. Seventy-three subjects were followed up at 5 years, 67 at 11 years, and 63 at 22 years. Results: Twenty-three (37%) adult subjects reported wheezing within the previous 12 months. Fifteen (25%) of these subjects showed signs of bronchial hyperresponsiveness and were regarded as asthmatic. Wheezing before the age of 2 years occurred in 28% and was not significantly related to adult asthma (odds ratio, 0.3; 95% CI, 0.03-1.7; P =.19). A positive skin prick test response to hen's egg, cow's milk, or both in the first year was independently predictive of adult asthma (odds ratio, 10.7; 95% CI, 2.1-55.1; P =.001; sensitivity, 57%; specificity, 89%). Conclusion: Prediction of adult asthma remains difficult. In this study of subjects at risk of atopy, skin sensitivity to hen's egg or cow's milk in the first year was predictive of adult asthma.. asthma| atopy| bronchial hyperresponsiveness| food allergen| aeroallergen| risk factors|allergic airway disease| dust mite allergen| serum ige| childhood asthma| lung-function| children| atopy| exposure| age| responsiveness.	NOV-2001	asthma| atopy| bronchial hyperresponsiveness| food allergen| aeroallergen| risk factors|allergic airway disease| dust mite allergen| serum ige| childhood asthma| lung-function| children| atopy| exposure| age| responsiveness	Rhodes, HL; Sporik, R; Thomas, P; Holgate, ST; Cogswell, JJ	Early life risk factors for adult asthma: A birth cohort study of subjects at risk		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; atopy; bronchial hyperresponsiveness; food allergen; aeroallergen; risk factors	ALLERGIC AIRWAY DISEASE; DUST MITE ALLERGEN; SERUM IGE; CHILDHOOD ASTHMA; LUNG-FUNCTION; CHILDREN; ATOPY; EXPOSURE; AGE; RESPONSIVENESS	Background: Prediction of adult asthma is important, and early prevention strategies should be targeted at those most at risk. Identifying high-risk children at an early age, however, is currently difficult. Objective: We sought to determine those factors present in early life that predict an increased risk of adult asthma. Methods: A prospective cohort study of subjects at risk of asthma and atopy was undertaken in Poole, England. One hundred babies of atopic parents were recruited at birth. During the first 5 years of life, subjects were recalled annually, all respiratory events were reported, and skin prick tests and total serum IgE measurements were performed. At 11 and 22 years, bronchial hyperresponsiveness was also measured. Seventy-three subjects were followed up at 5 years, 67 at 11 years, and 63 at 22 years. Results: Twenty-three (37%) adult subjects reported wheezing within the previous 12 months. Fifteen (25%) of these subjects showed signs of bronchial hyperresponsiveness and were regarded as asthmatic. Wheezing before the age of 2 years occurred in 28% and was not significantly related to adult asthma (odds ratio, 0.3; 95% CI, 0.03-1.7; P =.19). A positive skin prick test response to hen's egg, cow's milk, or both in the first year was independently predictive of adult asthma (odds ratio, 10.7; 95% CI, 2.1-55.1; P =.001; sensitivity, 57%; specificity, 89%). Conclusion: Prediction of adult asthma remains difficult. In this study of subjects at risk of atopy, skin sensitivity to hen's egg or cow's milk in the first year was predictive of adult asthma.	38	123	2001	6	10.1067/mai.2001.119151	Allergy; Immunology
Onset and persistence of childhood asthma: Predictors from infancy. family history of asthma, asthma onset by 3 years of age was found previously to be positively associated with variables from the first year of life, including elevated total immunoglobulin E (IgE), frequent respiratory infections, and parenting difficulties. We followed this cohort of genetically at-risk children to investigate the relationship between factors assessed in infancy and asthma, allergy, and psychological status at school age. Methods. A cohort of 150 children who were at risk for developing asthma were identified prenatally on the basis of the mothers' having asthma. For 28 children, the father had asthma as well, putting them at bilateral genetic risk. Families primarily were middle and upper middle class Caucasians. Parents came to the clinic during the third trimester of pregnancy for assessments of medical and psychosocial functioning. A home visit took place when the infant was 3 weeks old, when parenting risk was assessed before the onset of any asthma symptoms. Parenting difficulties included problems with infant caregiving as well as components of maternal functioning, such as postpartum depression and inadequate marital support. Blood was drawn for serum IgE at 6 months of age. Parents and offspring subsequently came to the clinic multiple times, with the last clinic visit during the child's sixth year. Follow-up at age 6 involved a clinic visit for allergy and psychosocial evaluations, consisting of interviews and a behavior questionnaire. Seventy-seven children received the allergy and psychosocial evaluation, 26 received the psychosocial evaluation in the clinic, and 30 families received telephone interviews and mailed in questionnaires. Additional monitoring of families by telephone and mail was maintained over the next 2 years, until the children were 8, to ensure accurate characterization of the course of illness. Comprehensive medical records were obtained and reviewed for all health care contacts. Children were designated as having asthma when there was documentation in medical records of physician-diagnosed asthma, observed wheezing, and/or prescription of asthma medications during the time period when the child was between 6 and 8 years of age. Parental reports of the occurrence of asthma corroborated the medical record data. Results. Data regarding asthma status were available for 145 children through 8 years of age. Forty (28%) of the children manifested asthma between 6 and 8 years of age. Among variables previously reported to predict asthma onset by age 3, 3 proved to have significant univariate relationships with asthma between ages 6 and 8: elevated IgE levels measured when the children were 6 months of age, global ratings of parenting difficulties measured when infants were 3 weeks old, and higher numbers of respiratory infections in the first year of life. Among these offspring of mothers with asthma, paternal asthma showed a significant association with asthma between ages 6 and 8. Eczema in the first year was not significantly related to later asthma. Multiple logistic regression showed that the model that best predicted asthma at ages 6 to 8 from infancy variables included 2 main effects. The adjusted odds ratio for 6-month IgE was 2.15 (1.51, 3.05) and for parenting difficulties was 2.07 (1.15, 3.71). Although socioeconomic status (SES) was not associated with asthma at ages 6 to 8, families of lower SES were more likely to be rated as having parenting difficulties early in the child's life. The mothers of lower SES breastfed for a shorter period of time and were more likely to smoke during their infant's first year. There were more respiratory infections during the first year of life among infants whose mother was rated as having more parenting difficulties. Mothers who reported smoking breastfed their infants for a shorter length of time. Male gender was significantly associated with higher IgE levels when infants were 6 months of age. Laboratory testing was completed for 77 children at age 6. Total serum IgE levels were significantly higher for the children with asthma between ages 6 and 8. Skin-prick testing showed that the children with asthma had significantly more positive skin test reactions than did the children without asthma. Psychosocial interview data at 6 years of age were available for 103 families, and behavioral questionnaires were available for 133 families. On the basis of 6-year interviews, children with asthma were rated as being at greater psychological risk than were the children without asthma. Mothers' Child Behavior Checklist (CBCL) ratings of their children's behavior indicated higher internalizing scores for the children with asthma as compared with the children without asthma. Like the 6-month IgE, 6-year IgE was higher for boys. IgE levels measured at 6 months of age were significantly correlated with 6-year IgE levels. Parenting difficulties measured at 3 weeks were significantly correlated with 6-year measures of maternal depression, CBCL Internalizing score, and Child Psychological Risk (CPR) score. There also were significant correlations among the psychosocial variables assessed when the children were 6 years of age; maternal depression was significantly associated with child CBCL Internalizing score and CPR score, and the last 2 also were significantly correlated. Multiple logistic regression showed that 2 concurrently measured variables entered the model showing the strongest associations with asthma at ages 6 to 8. The adjusted odds ratio for CPR score was 3.21 (1.29-7.96) and for 6-year IgE was 1.71 (1.04-2.80). Conclusions. This study of the natural history of childhood asthma focused on the development of asthma into the school-age years in a genetically at-risk group of children. The relationships between biological and psychosocial variables in the first year and school-age asthma support the formulation of asthma as beginning early in life, with the developing immune system interacting with environmental influences. The data provide support for the possible contribution of psychosocial factors to asthma onset and persistence into childhood.. pediatric asthma| parenting| ige allergy| psychosocial problems| risk| respiratory illness|risk-factors| natural-history| cord blood| children| stress| ige| mothers| hyperresponsiveness| sensitization| responses.	OCT-2001	pediatric asthma| parenting| ige allergy| psychosocial problems| risk| respiratory illness|risk-factors| natural-history| cord blood| children| stress| ige| mothers| hyperresponsiveness| sensitization| responses	Klinnert, MD; Nelson, HS; Price, MR; Adinoff, AD; Leung, DYM; Mrazek, DA	Onset and persistence of childhood asthma: Predictors from infancy		PEDIATRICS	pediatric asthma; parenting; IgE allergy; psychosocial problems; risk; respiratory illness	RISK-FACTORS; NATURAL-HISTORY; CORD BLOOD; CHILDREN; STRESS; IGE; MOTHERS; HYPERRESPONSIVENESS; SENSITIZATION; RESPONSES	family history of asthma, asthma onset by 3 years of age was found previously to be positively associated with variables from the first year of life, including elevated total immunoglobulin E (IgE), frequent respiratory infections, and parenting difficulties. We followed this cohort of genetically at-risk children to investigate the relationship between factors assessed in infancy and asthma, allergy, and psychological status at school age. Methods. A cohort of 150 children who were at risk for developing asthma were identified prenatally on the basis of the mothers' having asthma. For 28 children, the father had asthma as well, putting them at bilateral genetic risk. Families primarily were middle and upper middle class Caucasians. Parents came to the clinic during the third trimester of pregnancy for assessments of medical and psychosocial functioning. A home visit took place when the infant was 3 weeks old, when parenting risk was assessed before the onset of any asthma symptoms. Parenting difficulties included problems with infant caregiving as well as components of maternal functioning, such as postpartum depression and inadequate marital support. Blood was drawn for serum IgE at 6 months of age. Parents and offspring subsequently came to the clinic multiple times, with the last clinic visit during the child's sixth year. Follow-up at age 6 involved a clinic visit for allergy and psychosocial evaluations, consisting of interviews and a behavior questionnaire. Seventy-seven children received the allergy and psychosocial evaluation, 26 received the psychosocial evaluation in the clinic, and 30 families received telephone interviews and mailed in questionnaires. Additional monitoring of families by telephone and mail was maintained over the next 2 years, until the children were 8, to ensure accurate characterization of the course of illness. Comprehensive medical records were obtained and reviewed for all health care contacts. Children were designated as having asthma when there was documentation in medical records of physician-diagnosed asthma, observed wheezing, and/or prescription of asthma medications during the time period when the child was between 6 and 8 years of age. Parental reports of the occurrence of asthma corroborated the medical record data. Results. Data regarding asthma status were available for 145 children through 8 years of age. Forty (28%) of the children manifested asthma between 6 and 8 years of age. Among variables previously reported to predict asthma onset by age 3, 3 proved to have significant univariate relationships with asthma between ages 6 and 8: elevated IgE levels measured when the children were 6 months of age, global ratings of parenting difficulties measured when infants were 3 weeks old, and higher numbers of respiratory infections in the first year of life. Among these offspring of mothers with asthma, paternal asthma showed a significant association with asthma between ages 6 and 8. Eczema in the first year was not significantly related to later asthma. Multiple logistic regression showed that the model that best predicted asthma at ages 6 to 8 from infancy variables included 2 main effects. The adjusted odds ratio for 6-month IgE was 2.15 (1.51, 3.05) and for parenting difficulties was 2.07 (1.15, 3.71). Although socioeconomic status (SES) was not associated with asthma at ages 6 to 8, families of lower SES were more likely to be rated as having parenting difficulties early in the child's life. The mothers of lower SES breastfed for a shorter period of time and were more likely to smoke during their infant's first year. There were more respiratory infections during the first year of life among infants whose mother was rated as having more parenting difficulties. Mothers who reported smoking breastfed their infants for a shorter length of time. Male gender was significantly associated with higher IgE levels when infants were 6 months of age. Laboratory testing was completed for 77 children at age 6. Total serum IgE levels were significantly higher for the children with asthma between ages 6 and 8. Skin-prick testing showed that the children with asthma had significantly more positive skin test reactions than did the children without asthma. Psychosocial interview data at 6 years of age were available for 103 families, and behavioral questionnaires were available for 133 families. On the basis of 6-year interviews, children with asthma were rated as being at greater psychological risk than were the children without asthma. Mothers' Child Behavior Checklist (CBCL) ratings of their children's behavior indicated higher internalizing scores for the children with asthma as compared with the children without asthma. Like the 6-month IgE, 6-year IgE was higher for boys. IgE levels measured at 6 months of age were significantly correlated with 6-year IgE levels. Parenting difficulties measured at 3 weeks were significantly correlated with 6-year measures of maternal depression, CBCL Internalizing score, and Child Psychological Risk (CPR) score. There also were significant correlations among the psychosocial variables assessed when the children were 6 years of age; maternal depression was significantly associated with child CBCL Internalizing score and CPR score, and the last 2 also were significantly correlated. Multiple logistic regression showed that 2 concurrently measured variables entered the model showing the strongest associations with asthma at ages 6 to 8. The adjusted odds ratio for CPR score was 3.21 (1.29-7.96) and for 6-year IgE was 1.71 (1.04-2.80). Conclusions. This study of the natural history of childhood asthma focused on the development of asthma into the school-age years in a genetically at-risk group of children. The relationships between biological and psychosocial variables in the first year and school-age asthma support the formulation of asthma as beginning early in life, with the developing immune system interacting with environmental influences. The data provide support for the possible contribution of psychosocial factors to asthma onset and persistence into childhood.	54	123	2001	8	10.1542/peds.108.4.e69	Pediatrics
Th type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-gamma-dependent mechanism. In the mucosal immune system, resident dendritic cells are specialized for priming Th2-polarized immunity, whereas the Ag-presenting activity of macrophages has been linked with the development of Th1 phenotype. As an immune switch toward Th1 can protect against Th2-mediated allergic response, this study investigated the capacity of lung macrophages to stimulate Th1 responses during the secondary exposure to inhaled allergen, thereby suppressing Th2-mediated allergic airway inflammation in a murine model of allergic asthma. Following airway macrophage depletion in OVA-sensitized mice, lung T cells defaulted to a phenotype that produced less Th1 (IFN-gamma) and more Th2 (IL-4 and IL-5) cytokines, leading to more severe airway hyperreactivity and inflammation after intranasal Ag challenge. After OVA pulsing and adoptive transfer, lung macrophages selectively promoted a Th1 response in Ag-sensitized recipients and did not induce pulmonary eosinophilia. By contrast, OVA pulsing and adoptive transfer of a lung cell preparation, consisting of dendritic cells, B cells, and macrophages, promoted a Th2 response with an associated inflammatory response that was suppressed when macrophages were present and pretreated with IFN-gamma, but exacerbated when macrophages were depleted before IFN-gamma treatment. In addition, Th1-promoting activity of lung macrophages was not related to the autocrine production of IL-12p40. These results suggest that the Th1-promoting APC activity may be an inherent property of the lung macrophage population, and may play an important role, upon stimulation by IFN-gamma, in antagonizing an ongoing Th2 immunity and Th2-dependent allergic responses.. antigen-presenting cells| dendritic cells| alveolar macrophages| immune-responses| il-12 production| inhaled antigen| down-regulation| mice| induction| asthma.	FEB 1-2001	antigen-presenting cells| dendritic cells| alveolar macrophages| immune-responses| il-12 production| inhaled antigen| down-regulation| mice| induction| asthma	Tang, CB; Inman, MD; van Rooijen, N; Yang, PC; Shen, HH; Matsumoto, K; O'Byrne, PM	Th type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-gamma-dependent mechanism		JOURNAL OF IMMUNOLOGY		ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; ALVEOLAR MACROPHAGES; IMMUNE-RESPONSES; IL-12 PRODUCTION; INHALED ANTIGEN; DOWN-REGULATION; MICE; INDUCTION; ASTHMA	In the mucosal immune system, resident dendritic cells are specialized for priming Th2-polarized immunity, whereas the Ag-presenting activity of macrophages has been linked with the development of Th1 phenotype. As an immune switch toward Th1 can protect against Th2-mediated allergic response, this study investigated the capacity of lung macrophages to stimulate Th1 responses during the secondary exposure to inhaled allergen, thereby suppressing Th2-mediated allergic airway inflammation in a murine model of allergic asthma. Following airway macrophage depletion in OVA-sensitized mice, lung T cells defaulted to a phenotype that produced less Th1 (IFN-gamma) and more Th2 (IL-4 and IL-5) cytokines, leading to more severe airway hyperreactivity and inflammation after intranasal Ag challenge. After OVA pulsing and adoptive transfer, lung macrophages selectively promoted a Th1 response in Ag-sensitized recipients and did not induce pulmonary eosinophilia. By contrast, OVA pulsing and adoptive transfer of a lung cell preparation, consisting of dendritic cells, B cells, and macrophages, promoted a Th2 response with an associated inflammatory response that was suppressed when macrophages were present and pretreated with IFN-gamma, but exacerbated when macrophages were depleted before IFN-gamma treatment. In addition, Th1-promoting activity of lung macrophages was not related to the autocrine production of IL-12p40. These results suggest that the Th1-promoting APC activity may be an inherent property of the lung macrophage population, and may play an important role, upon stimulation by IFN-gamma, in antagonizing an ongoing Th2 immunity and Th2-dependent allergic responses.	50	123	2001	11		Immunology
Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: A prospective, randomized study. The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High-risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five-hundred and ninety-five high-risk infants were identified. Nigh-risk infants were defined as having biparental atopy, or a single atopic first-degree relative combined with cord blood immunoglobulin E (IgE) greater than or equal to 0.3 kU/l, At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively. If breastfeeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk-based formula were given when needed. All infants were followed-up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to noncompliance. Of 478 infants who completed the study, 232 were exclusively breast-fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan WA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breastfed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast-feeding was high; only eight (2%) children were not breast-fed at all. The three formula groups were identical in regard to duration of breast-feeding: and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental-reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast-fed infants, 0.6% tone of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 3 months.. hypoallergenic infant formula| protein hydrolysates| allergy prevention| cow's milk allergy| pediatric|high-risk infants| partial whey hydrolysate| cow milk formulas| atopic disease| follow-up| avoidance| prophylaxis| soy| age| disorders.	AUG-2000	hypoallergenic infant formula| protein hydrolysates| allergy prevention| cow's milk allergy| pediatric|high-risk infants| partial whey hydrolysate| cow milk formulas| atopic disease| follow-up| avoidance| prophylaxis| soy| age| disorders	Halken, S; Hansen, KS; Jacobsen, HP; Estmann, A; Faelling, AE; Hansen, LG; Kier, SR; Lassen, K; Lintrup, M; Mortensen, S; Ibsen, KK; Osterballe, O; Host, A	Comparison of a partially hydrolyzed infant formula with two extensively hydrolyzed formulas for allergy prevention: A prospective, randomized study		PEDIATRIC ALLERGY AND IMMUNOLOGY	hypoallergenic infant formula; protein hydrolysates; allergy prevention; cow's milk allergy; pediatric	HIGH-RISK INFANTS; PARTIAL WHEY HYDROLYSATE; COW MILK FORMULAS; ATOPIC DISEASE; FOLLOW-UP; AVOIDANCE; PROPHYLAXIS; SOY; AGE; DISORDERS	The aim of this study was to compare the allergy-preventive effect of a partially hydrolyzed formula with two extensively hydrolyzed formulas, in infants with a high risk for development of allergic disease. High-risk infants from four Danish centres were included in the period from June 1994 to July 1995. Five-hundred and ninety-five high-risk infants were identified. Nigh-risk infants were defined as having biparental atopy, or a single atopic first-degree relative combined with cord blood immunoglobulin E (IgE) greater than or equal to 0.3 kU/l, At birth all infants were randomized to one of three different blinded formulas. All mothers had unrestricted diets during pregnancy and lactation and were encouraged to breast-feed exclusively. If breastfeeding was insufficient, one of the three formulas, according to randomization, was given during the first 4 months. It was recommended not to introduce cow's milk, cow's milk products, and solid foods until the age of 4 months. After the age of 4 months a normal unrestricted diet and conventional cow's milk-based formula were given when needed. All infants were followed-up prospectively with interview and physical examination at the age of 6, 12, and 18 months, and if any possible atopic symptoms were reported. If food allergy was suspected, controlled elimination/challenge procedures were performed in a hospital setting. Of 550 infants included in the study, 514 were seen at all visits and 36 were excluded owing to noncompliance. Of 478 infants who completed the study, 232 were exclusively breast-fed, 79 received an extensively hydrolyzed casein formula (Nutramigen), 82 an extensively hydrolyzed whey formula (Profylac), and 85 a partially hydrolyzed whey formula (Nan WA), during the first 4 months of life. These four groups were identical in regard to atopic predisposition, cord blood IgE, birthplace, and gender. Exclusively breastfed children were exposed less to tobacco smoke and pets at home and belonged to higher social classes, whereas the three formula groups were identical concerning environmental factors. The frequency of breast-feeding was high; only eight (2%) children were not breast-fed at all. The three formula groups were identical in regard to duration of breast-feeding: and age at introduction of formula and solid foods. No significant differences were found in the three groups of infants receiving formula milk regarding the cumulative incidence of atopic dermatitis or respiratory symptoms. The cumulative incidence of parental-reported cow's milk allergy was significantly higher in children fed partially hydrolyzed formula (Nan HA) compared with extensively hydrolyzed formula (Nutramigen or Profylac) at 12 and 18 months (NanHA, 7.1%; Nutramigen, 2.5%; Profylac, 0%; p = 0.033). The cumulative incidence of confirmed cow's milk allergy was 1.3% (three of 232) in exclusively breast-fed infants, 0.6% tone of 161) in infants fed extensively hydrolyzed formula (Nutramigen or Profylac), and 4.7% (four of 85) in infants fed partially hydrolyzed formula (Nan HA). Partially hydrolyzed formula was found to be less effective than extensively hydrolyzed formula in preventing cow's milk allergy, 0.6% vs. 4.7% (p = 0.05), but because of the small number of cases the results should be interpreted with caution. Compared with other similar studies the frequency of atopic symptoms was low, even though the dietetic intervention did not include either maternal diet during lactation or dietary restrictions to the children after the age of 3 months.	29	123	2000	13	10.1034/j.1399-3038.2000.00081.x	Allergy; Immunology; Pediatrics
Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics. Asthma is characterized by chronic airway inflammation resulting from overproduction of pro-inflammatory mediators, such as leukotrienes (LT), The authors questioned the biosynthetic capacity of asthmatic patients for lipoxins (LX) and 15-epimer lipoxins (15-epi-LX), endogenous regulators of inflammatory responses that inhibit pro-inflammatory events, Levels of LXA(4), 15-epi-LXA(4) and LTC4 were determined in 14 clinically characterized aspirin-intolerant asthmatics (AIA), 11 aspirin-tolerant asthmatics (ATh) and eight healthy volunteers using a stimulated whole blood protocol, Both LXA(4) and 15-epi-LXA(4) were generated in whole blood activated by the divalent cation ionophore, A23187, Higher levels of LXA(4) were produced in ATA than either AIA or healthy volunteers, Exposure of AIA whole blood to interleukin-3 prior to A23187 did not elevate their reduced capacity to generate LXA(4). Generation of a bronchoconstrictor, LTC4, was similar in both AIA and ATA, Consequently, the ratio of LXA(4):LTC4 quantitatively favoured the bronchoconstrictor for AIA and differed from both ATA and healthy subjects. In addition, the capacity for 15-epi-LXA(4) generation was also diminished in AIA, since whole blood stimulated in the presence of aspirin gave increased levels only in samples from ATA, The present results indicate that asthmatics possess the capacity to generate both lipoxins and 15-epimer-lipoxins, but aspirin-intolerant asthmatics display a lower biosynthetic capacity than aspirin-tolerant asthmatics for these potentially protective lipid mediators. This previously unappreciated, diminished capacity for lipoxin formation by aspirin-intolerant asthmatic patients may contribute to their more severe clinical phenotype, and represents a novel paradigm for the development of chronic inflammatory disorders.. anti-inflammatory mediators| aspirin-intolerant asthma| cysteinyl-leukotrienes| lipoxins|sensitive asthmatics| bronchial biopsies| nasal polyps| leukotriene-e4| inhibition| responses| synthase| fluids| acid| atl.	JUL-2000	anti-inflammatory mediators| aspirin-intolerant asthma| cysteinyl-leukotrienes| lipoxins|sensitive asthmatics| bronchial biopsies| nasal polyps| leukotriene-e4| inhibition| responses| synthase| fluids| acid| atl	Sanak, M; Levy, BD; Clish, CB; Chiang, N; Gronert, K; Mastalerz, L; Serhan, CN; Szczeklik, A	Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics		EUROPEAN RESPIRATORY JOURNAL	anti-inflammatory mediators; aspirin-intolerant asthma; cysteinyl-leukotrienes; lipoxins	SENSITIVE ASTHMATICS; BRONCHIAL BIOPSIES; NASAL POLYPS; LEUKOTRIENE-E4; INHIBITION; RESPONSES; SYNTHASE; FLUIDS; ACID; ATL	Asthma is characterized by chronic airway inflammation resulting from overproduction of pro-inflammatory mediators, such as leukotrienes (LT), The authors questioned the biosynthetic capacity of asthmatic patients for lipoxins (LX) and 15-epimer lipoxins (15-epi-LX), endogenous regulators of inflammatory responses that inhibit pro-inflammatory events, Levels of LXA(4), 15-epi-LXA(4) and LTC4 were determined in 14 clinically characterized aspirin-intolerant asthmatics (AIA), 11 aspirin-tolerant asthmatics (ATh) and eight healthy volunteers using a stimulated whole blood protocol, Both LXA(4) and 15-epi-LXA(4) were generated in whole blood activated by the divalent cation ionophore, A23187, Higher levels of LXA(4) were produced in ATA than either AIA or healthy volunteers, Exposure of AIA whole blood to interleukin-3 prior to A23187 did not elevate their reduced capacity to generate LXA(4). Generation of a bronchoconstrictor, LTC4, was similar in both AIA and ATA, Consequently, the ratio of LXA(4):LTC4 quantitatively favoured the bronchoconstrictor for AIA and differed from both ATA and healthy subjects. In addition, the capacity for 15-epi-LXA(4) generation was also diminished in AIA, since whole blood stimulated in the presence of aspirin gave increased levels only in samples from ATA, The present results indicate that asthmatics possess the capacity to generate both lipoxins and 15-epimer-lipoxins, but aspirin-intolerant asthmatics display a lower biosynthetic capacity than aspirin-tolerant asthmatics for these potentially protective lipid mediators. This previously unappreciated, diminished capacity for lipoxin formation by aspirin-intolerant asthmatic patients may contribute to their more severe clinical phenotype, and represents a novel paradigm for the development of chronic inflammatory disorders.	29	123	2000	6	10.1034/j.1399-3003.2000.16a08.x	Respiratory System
Update on risk factors for food allergy. Despite efforts to prevent food allergy (FA) in children, IgE-mediated FAs are increasing in westernized countries. Previous preventive strategies, such as prolonged exclusive breast-feeding and delayed weaning onto solid foods, have recently been called into question. The present review considers possible risk factors and theories for the development of FA. An alternative hypothesis is proposed, suggesting that early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitization and that early oral exposure to food allergen induces tolerance. Novel interventional strategies to prevent the development of FA are also discussed. (J Allergy Clin Immunol 2012;129:1187-97.). food allergy| risk factors| filaggrin| genetics| dual-allergen-exposure hypothesis|oral tolerance induction| of-function mutations| peanut allergy| atopic-dermatitis| united-states| gene polymorphisms| function variants| early-childhood| maternal diet| nut allergy.	MAY-2012	food allergy| risk factors| filaggrin| genetics| dual-allergen-exposure hypothesis|oral tolerance induction| of-function mutations| peanut allergy| atopic-dermatitis| united-states| gene polymorphisms| function variants| early-childhood| maternal diet| nut allergy	Lack, G	Update on risk factors for food allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Food allergy; risk factors; filaggrin; genetics; dual-allergen-exposure hypothesis	ORAL TOLERANCE INDUCTION; OF-FUNCTION MUTATIONS; PEANUT ALLERGY; ATOPIC-DERMATITIS; UNITED-STATES; GENE POLYMORPHISMS; FUNCTION VARIANTS; EARLY-CHILDHOOD; MATERNAL DIET; NUT ALLERGY	Despite efforts to prevent food allergy (FA) in children, IgE-mediated FAs are increasing in westernized countries. Previous preventive strategies, such as prolonged exclusive breast-feeding and delayed weaning onto solid foods, have recently been called into question. The present review considers possible risk factors and theories for the development of FA. An alternative hypothesis is proposed, suggesting that early cutaneous exposure to food protein through a disrupted skin barrier leads to allergic sensitization and that early oral exposure to food allergen induces tolerance. Novel interventional strategies to prevent the development of FA are also discussed. (J Allergy Clin Immunol 2012;129:1187-97.)	85	122	2012	11	10.1016/j.jaci.2012.02.036	Allergy; Immunology
Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergen immunotherapy reorients inappropriate immune responses in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical tolerance. Although 4075% of patients receiving SLIT experience mild, transient local reactions in the oral mucosa, these primary reactions rarely necessitate dose reduction or treatment interruption. We discuss 11 published case reports of anaphylaxis (all nonfatal) diagnosed according to the World Allergy Organization criteria and relate this figure to the approximately 1 billion SLIT doses administered worldwide since 2000. Anaphylaxis risk factors associated with SCIT and/or SLIT should be characterized further.. allergen immunotherapy| mucosal| safety| subcutaneous| sublingual|systemic reactions| double-dummy| double-blind| anaphylaxis| rhinitis| organization| asthma| efficacy| injections| frequency.	MAR-2012	allergen immunotherapy| mucosal| safety| subcutaneous| sublingual|systemic reactions| double-dummy| double-blind| anaphylaxis| rhinitis| organization| asthma| efficacy| injections| frequency	Calderon, MA; Simons, FER; Malling, HJ; Lockey, RF; Moingeon, P; Demoly, P	Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile		ALLERGY	allergen immunotherapy; mucosal; safety; subcutaneous; sublingual	SYSTEMIC REACTIONS; DOUBLE-DUMMY; DOUBLE-BLIND; ANAPHYLAXIS; RHINITIS; ORGANIZATION; ASTHMA; EFFICACY; INJECTIONS; FREQUENCY	Allergen immunotherapy reorients inappropriate immune responses in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical tolerance. Although 4075% of patients receiving SLIT experience mild, transient local reactions in the oral mucosa, these primary reactions rarely necessitate dose reduction or treatment interruption. We discuss 11 published case reports of anaphylaxis (all nonfatal) diagnosed according to the World Allergy Organization criteria and relate this figure to the approximately 1 billion SLIT doses administered worldwide since 2000. Anaphylaxis risk factors associated with SCIT and/or SLIT should be characterized further.	42	122	2012	10	10.1111/j.1398-9995.2011.02761.x	Allergy; Immunology
Urban Air Pollution and Climate Change as Environmental Risk Factors of Respiratory Allergy: An Update. The incidence of allergic respiratory diseases and bronchial asthma appears to be increasing worldwide, and people living in urban areas more frequently experience these conditions than those living in rural areas. One of the several causes of the rise in morbidity associated with allergic respiratory diseases is the increased presence of outdoor air pollutants resulting from more intense energy consumption and exhaust emissions from cars and other vehicles. Urban air pollution is now a serious public health hazard. Laboratory studies confirm epidemiologic evidence that air pollution adversely affects lung function in asthmatics. Damage to airway mucous membranes and impaired mucociliary clearance caused by air pollution may facilitate access of inhaled allergens to the cells of the immune system, thus promoting sensitization of the airway. Consequently, a more severe immunoglobulin (Ig) E-mediated response to aeroallergens and airway inflammation could account for increasing prevalence of allergic respiratory diseases in polluted urban areas. The most abundant components of urban air pollution in urban areas with high levels of vehicle traffic are airborne particulate matter, nitrogen dioxide, and ozone. In addition, the earth's temperature is increasing, mainly as a result of anthropogenic factors (eg, fossil fuel combustion and greenhouse gas emissions from energy supply, transport, industry, and agriculture), and climate change alters the concentration and distribution of air pollutants and interferes with the seasonal presence of allergenic pollens in the atmosphere by prolonging these periods.. air pollution| allergy| allergic asthma| bronchial asthma| climate change| environmental diseases| airway hyperreactivity| pollen allergy| respiratory allergy| urban air pollution| hypersensitivity|lung-function growth| southern california children| case-crossover analysis| heat-related mortality| particulate matter| childhood asthma| school-children| bronchial-asthma| european cities| pollen allergy.	2010	air pollution| allergy| allergic asthma| bronchial asthma| climate change| environmental diseases| airway hyperreactivity| pollen allergy| respiratory allergy| urban air pollution| hypersensitivity|lung-function growth| southern california children| case-crossover analysis| heat-related mortality| particulate matter| childhood asthma| school-children| bronchial-asthma| european cities| pollen allergy	D'Amato, G; Cecchi, L; D'Amato, M; Liccardi, G	Urban Air Pollution and Climate Change as Environmental Risk Factors of Respiratory Allergy: An Update		JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY	Air pollution; Allergy; Allergic asthma; Bronchial asthma; Climate change; Environmental diseases; Airway hyperreactivity; Pollen allergy; Respiratory allergy; Urban air pollution; Hypersensitivity	LUNG-FUNCTION GROWTH; SOUTHERN CALIFORNIA CHILDREN; CASE-CROSSOVER ANALYSIS; HEAT-RELATED MORTALITY; PARTICULATE MATTER; CHILDHOOD ASTHMA; SCHOOL-CHILDREN; BRONCHIAL-ASTHMA; EUROPEAN CITIES; POLLEN ALLERGY	The incidence of allergic respiratory diseases and bronchial asthma appears to be increasing worldwide, and people living in urban areas more frequently experience these conditions than those living in rural areas. One of the several causes of the rise in morbidity associated with allergic respiratory diseases is the increased presence of outdoor air pollutants resulting from more intense energy consumption and exhaust emissions from cars and other vehicles. Urban air pollution is now a serious public health hazard. Laboratory studies confirm epidemiologic evidence that air pollution adversely affects lung function in asthmatics. Damage to airway mucous membranes and impaired mucociliary clearance caused by air pollution may facilitate access of inhaled allergens to the cells of the immune system, thus promoting sensitization of the airway. Consequently, a more severe immunoglobulin (Ig) E-mediated response to aeroallergens and airway inflammation could account for increasing prevalence of allergic respiratory diseases in polluted urban areas. The most abundant components of urban air pollution in urban areas with high levels of vehicle traffic are airborne particulate matter, nitrogen dioxide, and ozone. In addition, the earth's temperature is increasing, mainly as a result of anthropogenic factors (eg, fossil fuel combustion and greenhouse gas emissions from energy supply, transport, industry, and agriculture), and climate change alters the concentration and distribution of air pollutants and interferes with the seasonal presence of allergenic pollens in the atmosphere by prolonging these periods.	98	122	2010	8		Allergy; Immunology
Extreme High Temperatures and Hospital Admissions for Respiratory and Cardiovascular Diseases. Background: Although the association of high temperatures with mortality is well-documented, the association with morbidity has seldom been examined. We assessed the potential impact of hot weather on hospital admissions due to cardiovascular and respiratory diseases in New York City. We also explored whether the weather-disease relationship varies with socio-demographic variables. Method: We investigated effects of temperature and humidity on health by linking the daily cardiovascular and respiratory hospitalization counts with meteorologic conditions during summer, 1991-2004. We used daily mean temperature, mean apparent temperature, and 3-day moving average of apparent temperature as the exposure indicators. Threshold effects for health risks of meteorologic conditions were assessed by log-linear threshold models, after controlling for ozone, day of week, holidays, and long-term trend. Stratified analyses were used to evaluate temperature-demographic interactions. Results: For all 3 exposure indicators, each degree C above the threshold of the temperature-health effect curve (29 degrees C-36 degrees C) was associated with a 2.7%-3.1% increase in same-day hospitalizations due to respiratory diseases, and an increase of 1.4%-3.6% in lagged hospitalizations due to cardiovascular diseases. These increases for respiratory admissions were greater for Hispanic persons (6.1%/degrees C) and the elderly (4.7%/degrees C). At high temperatures, admission rates increased for chronic airway obstruction, asthma, ischemic heart disease, and cardiac dysrhythmias, but decreased for hypertension and heart failure. Conclusions: Extreme high temperature appears to increase hospital admissions for cardiovascular and respiratory disorders in New York City. Elderly and Hispanic residents may be particularly vulnerable to the temperature effects on respiratory illnesses.. heat-related mortality| ambient-temperature| air-pollution| european cities| united-states| time-series| morbidity| city| wave| humidity.	SEP-2009	heat-related mortality| ambient-temperature| air-pollution| european cities| united-states| time-series| morbidity| city| wave| humidity	Lin, S; Luo, M; Walker, RJ; Liu, X; Hwang, SA; Chinery, R	Extreme High Temperatures and Hospital Admissions for Respiratory and Cardiovascular Diseases		EPIDEMIOLOGY		HEAT-RELATED MORTALITY; AMBIENT-TEMPERATURE; AIR-POLLUTION; EUROPEAN CITIES; UNITED-STATES; TIME-SERIES; MORBIDITY; CITY; WAVE; HUMIDITY	Background: Although the association of high temperatures with mortality is well-documented, the association with morbidity has seldom been examined. We assessed the potential impact of hot weather on hospital admissions due to cardiovascular and respiratory diseases in New York City. We also explored whether the weather-disease relationship varies with socio-demographic variables. Method: We investigated effects of temperature and humidity on health by linking the daily cardiovascular and respiratory hospitalization counts with meteorologic conditions during summer, 1991-2004. We used daily mean temperature, mean apparent temperature, and 3-day moving average of apparent temperature as the exposure indicators. Threshold effects for health risks of meteorologic conditions were assessed by log-linear threshold models, after controlling for ozone, day of week, holidays, and long-term trend. Stratified analyses were used to evaluate temperature-demographic interactions. Results: For all 3 exposure indicators, each degree C above the threshold of the temperature-health effect curve (29 degrees C-36 degrees C) was associated with a 2.7%-3.1% increase in same-day hospitalizations due to respiratory diseases, and an increase of 1.4%-3.6% in lagged hospitalizations due to cardiovascular diseases. These increases for respiratory admissions were greater for Hispanic persons (6.1%/degrees C) and the elderly (4.7%/degrees C). At high temperatures, admission rates increased for chronic airway obstruction, asthma, ischemic heart disease, and cardiac dysrhythmias, but decreased for hypertension and heart failure. Conclusions: Extreme high temperature appears to increase hospital admissions for cardiovascular and respiratory disorders in New York City. Elderly and Hispanic residents may be particularly vulnerable to the temperature effects on respiratory illnesses.	38	122	2009	9	10.1097/EDE.0b013e3181ad5522	Public, Environmental & Occupational Health
Inhibition of PI3K delta Restores Glucocorticoid Function in Smoking-induced Airway Inflammation in Mice. Rationale. There is an increasing prevalence of reduced responsiveness to glucocorticoid therapy in severe asthma and chronic obstructive pulmonary disease (COPD). The molecular mechanism of this remains unknown. Recent studies have shown that histone deacetylase activity, which is critical to glucocorticoid function, is altered by oxidant stress and may be involved in the development of glucocorticoid insensitivity. Objectives: To determine the role of phosphoinositol-3-kinase (PI3K) in the development of cigarette smoke-induced glucocorticoid insensitivity. Methods: Wild-type, PI3K gamma knock-out and PI3K delta kinase dead knock-in transgenic mice were used in a model of cigarette smoke-induced glucocorticoid insensitivity. Peripheral lung tissue was obtained from six healthy nonsmokers, nine smokers with normal lung function, and eight patients with COPD. Measurements and Main Results: In vitro oxidative stress activates PI3K and induced a relative glucocorticoid resistance, which is restored by PI3K inhibition. In vivo, cigarette smoke exposure in mice increased tyrosine nitration of histone deacetylase 2 in the lung, correlating with reduced histone deacetylase 2 activity and reduced glucocorticoid function. Histone deacetylase 2 activity and the antiinflammatory effects of glucocorticoids were restored in PI3K delta kinase dead knock-in but not PI3K gamma knock-out smoke-exposed mice compared with wild type mice, correlating with reduced histone deacetylase 2 tyrosine nitration. Glucocorticoid receptor expression was significantly reduced in smoke-exposed mice, in smokers with normal lung function, and in patients with COPD. Conclusions: These data show that therapeutic inhibition of PI3K delta may restore glucocorticoid function in oxidative stress-induced glucocorticoid insensitivity.. inflammation| histone deacetylase| chromatin| oxidative stress|obstructive pulmonary-disease| histone deacetylase activity| phosphoinositide 3-kinase| gene-expression| receptor| activation| asthma| theophylline| p110-delta| pathogenesis.	APR 1-2009	inflammation| histone deacetylase| chromatin| oxidative stress|obstructive pulmonary-disease| histone deacetylase activity| phosphoinositide 3-kinase| gene-expression| receptor| activation| asthma| theophylline| p110-delta| pathogenesis	Marwick, JA; Caramori, G; Stevenson, CS; Casolari, P; Jazrawi, E; Barnes, PJ; Ito, K; Adcock, IM; Kirkham, PA; Papi, A	Inhibition of PI3K delta Restores Glucocorticoid Function in Smoking-induced Airway Inflammation in Mice		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	inflammation; histone deacetylase; chromatin; oxidative stress	OBSTRUCTIVE PULMONARY-DISEASE; HISTONE DEACETYLASE ACTIVITY; PHOSPHOINOSITIDE 3-KINASE; GENE-EXPRESSION; RECEPTOR; ACTIVATION; ASTHMA; THEOPHYLLINE; P110-DELTA; PATHOGENESIS	Rationale. There is an increasing prevalence of reduced responsiveness to glucocorticoid therapy in severe asthma and chronic obstructive pulmonary disease (COPD). The molecular mechanism of this remains unknown. Recent studies have shown that histone deacetylase activity, which is critical to glucocorticoid function, is altered by oxidant stress and may be involved in the development of glucocorticoid insensitivity. Objectives: To determine the role of phosphoinositol-3-kinase (PI3K) in the development of cigarette smoke-induced glucocorticoid insensitivity. Methods: Wild-type, PI3K gamma knock-out and PI3K delta kinase dead knock-in transgenic mice were used in a model of cigarette smoke-induced glucocorticoid insensitivity. Peripheral lung tissue was obtained from six healthy nonsmokers, nine smokers with normal lung function, and eight patients with COPD. Measurements and Main Results: In vitro oxidative stress activates PI3K and induced a relative glucocorticoid resistance, which is restored by PI3K inhibition. In vivo, cigarette smoke exposure in mice increased tyrosine nitration of histone deacetylase 2 in the lung, correlating with reduced histone deacetylase 2 activity and reduced glucocorticoid function. Histone deacetylase 2 activity and the antiinflammatory effects of glucocorticoids were restored in PI3K delta kinase dead knock-in but not PI3K gamma knock-out smoke-exposed mice compared with wild type mice, correlating with reduced histone deacetylase 2 tyrosine nitration. Glucocorticoid receptor expression was significantly reduced in smoke-exposed mice, in smokers with normal lung function, and in patients with COPD. Conclusions: These data show that therapeutic inhibition of PI3K delta may restore glucocorticoid function in oxidative stress-induced glucocorticoid insensitivity.	35	122	2009	7	10.1164/rccm.200810-1570OC	General & Internal Medicine; Respiratory System
Children's response to air pollutants. It is important to focus on children with respect to air pollution because (1) their lungs are not completely developed, (2) they can have greater exposures than adults, and (3) those exposures can deliver higher doses of different composition that may remain in the lung for greater duration. The undeveloped lung is more vulnerable to assault and less able to fully repair itself when injury disrupts morphogenesis. Children spend more time outside, where concentrations of combustion-generated air pollution are generally higher. Children have higher baseline ventilation rates and are more physically active than adults, thus exposing their lungs to more air pollution. Nasal breathing in adults reduces some pollution concentrations, but children are more typically mouth-breathers - suggesting that the composition of the exposure mixture at the alveolar level may be different. Finally, higher ventilation rates and mouth-breathing may pull air pollutants deeper into children's lungs, thereby making clearance slower and more difficult. Children also have immature immune systems, which plays a significant role in asthma. The observed consequences of early life exposure to adverse levels of air pollutants include diminished lung function and increased susceptibility to acute respiratory illness and asthma. Exposure to diesel exhaust, in particular, is an area of concern for multiple endpoints, and deserves further research.. environmental tobacco-smoke| low-birth-weight| postneonatal infant-mortality| southern california children| chronic respiratory symptoms| diesel exhaust particles| cross-sectional area| particulate matter| lung-function| american children.	2008	environmental tobacco-smoke| low-birth-weight| postneonatal infant-mortality| southern california children| chronic respiratory symptoms| diesel exhaust particles| cross-sectional area| particulate matter| lung-function| american children	Bateson, TF; Schwartz, J	Children's response to air pollutants		JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES		ENVIRONMENTAL TOBACCO-SMOKE; LOW-BIRTH-WEIGHT; POSTNEONATAL INFANT-MORTALITY; SOUTHERN CALIFORNIA CHILDREN; CHRONIC RESPIRATORY SYMPTOMS; DIESEL EXHAUST PARTICLES; CROSS-SECTIONAL AREA; PARTICULATE MATTER; LUNG-FUNCTION; AMERICAN CHILDREN	It is important to focus on children with respect to air pollution because (1) their lungs are not completely developed, (2) they can have greater exposures than adults, and (3) those exposures can deliver higher doses of different composition that may remain in the lung for greater duration. The undeveloped lung is more vulnerable to assault and less able to fully repair itself when injury disrupts morphogenesis. Children spend more time outside, where concentrations of combustion-generated air pollution are generally higher. Children have higher baseline ventilation rates and are more physically active than adults, thus exposing their lungs to more air pollution. Nasal breathing in adults reduces some pollution concentrations, but children are more typically mouth-breathers - suggesting that the composition of the exposure mixture at the alveolar level may be different. Finally, higher ventilation rates and mouth-breathing may pull air pollutants deeper into children's lungs, thereby making clearance slower and more difficult. Children also have immature immune systems, which plays a significant role in asthma. The observed consequences of early life exposure to adverse levels of air pollutants include diminished lung function and increased susceptibility to acute respiratory illness and asthma. Exposure to diesel exhaust, in particular, is an area of concern for multiple endpoints, and deserves further research.	83	122	2008	6	10.1080/15287390701598234	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Background: Exposure to microbial agents might inhibit the development of atopy and asthma. Objective: We measured the association between microbial exposure assessed at 3 months and the development of atopic sensitization and doctor-diagnosed (DD) asthma and wheeze in the first 4 years in a birth cohort study of children with atopic mothers. Methods: Endotoxin, fungal (1 -> 3)-beta-D-glucans, extracellular polysaccharides from the genera Penicillium and Aspergillus (EPS-Pen/Asp), and dust on living room floors were measured at 3 months of age. Serum IgE levels against common allergens were determined at 1 and 4 years, and questionnaire information about respiratory morbidity was collected yearly. Results: Microbial levels in mattresses were low and not associated with serum IgE levels, DD asthma, and wheeze. Floor levels of biocontaminants and dust, on the other hand, were inversely associated with DD asthma, being most pronounced for endotoxin (odds ratio [OR], 0.40; 95% CI, 0.210.77) and EPS-Pen/Asp (OR, 0.42; 95% CI, 0.18-0.99). Mutual adjustment for other exposures did not significantly after the results for endotoxin and only moderately affected the results for EPS-Pen/Asp. Persistent wheeze was also consistently less common in the high-exposure group, being significant only for EPS-PenlAsp (OR, 0.37; 95% CI, 0.15-0.96). Transient wheeze and wheeze in the past 12 months were also reduced, but effects were smaller and not significant. Relationships with serum-specific IgE levels, which could only be assessed in 41% at age 4 years, were less pronounced and statistically significant only for EPS-Pen/Asp. Conclusions: Early exposure to common microbial contaminants, including fungal agents, might protect against asthma. Clinical implications: Microbial exposure in early life might protect against asthma and might constitute a novel target for prevention.. asthma| allergy| endotoxin| (1 -> 3)-beta-d-glucan| hygiene hypothesis| infant cohort study|house-dust endotoxin| children| atopy| sensitization| infancy| life| polymorphism| wheeze| airway| cd14.	MAY-2006	asthma| allergy| endotoxin| (1 -> 3)-beta-d-glucan| hygiene hypothesis| infant cohort study|house-dust endotoxin| children| atopy| sensitization| infancy| life| polymorphism| wheeze| airway| cd14	Douwes, J; van Strien, R; Doekes, G; Smit, J; Kerkhof, M; Gerritsen, J; Postma, D; Travier, N; Brunekreef, B	Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; allergy; endotoxin; (1 -> 3)-beta-D-glucan; hygiene hypothesis; infant cohort study	HOUSE-DUST ENDOTOXIN; CHILDREN; ATOPY; SENSITIZATION; INFANCY; LIFE; POLYMORPHISM; WHEEZE; AIRWAY; CD14	Background: Exposure to microbial agents might inhibit the development of atopy and asthma. Objective: We measured the association between microbial exposure assessed at 3 months and the development of atopic sensitization and doctor-diagnosed (DD) asthma and wheeze in the first 4 years in a birth cohort study of children with atopic mothers. Methods: Endotoxin, fungal (1 -> 3)-beta-D-glucans, extracellular polysaccharides from the genera Penicillium and Aspergillus (EPS-Pen/Asp), and dust on living room floors were measured at 3 months of age. Serum IgE levels against common allergens were determined at 1 and 4 years, and questionnaire information about respiratory morbidity was collected yearly. Results: Microbial levels in mattresses were low and not associated with serum IgE levels, DD asthma, and wheeze. Floor levels of biocontaminants and dust, on the other hand, were inversely associated with DD asthma, being most pronounced for endotoxin (odds ratio [OR], 0.40; 95% CI, 0.210.77) and EPS-Pen/Asp (OR, 0.42; 95% CI, 0.18-0.99). Mutual adjustment for other exposures did not significantly after the results for endotoxin and only moderately affected the results for EPS-Pen/Asp. Persistent wheeze was also consistently less common in the high-exposure group, being significant only for EPS-PenlAsp (OR, 0.37; 95% CI, 0.15-0.96). Transient wheeze and wheeze in the past 12 months were also reduced, but effects were smaller and not significant. Relationships with serum-specific IgE levels, which could only be assessed in 41% at age 4 years, were less pronounced and statistically significant only for EPS-Pen/Asp. Conclusions: Early exposure to common microbial contaminants, including fungal agents, might protect against asthma. Clinical implications: Microbial exposure in early life might protect against asthma and might constitute a novel target for prevention.	30	122	2006	7	10.1016/j.jaci.2006.02.002	Allergy; Immunology
The transient receptor potential vanilloid 1: Role in airway inflammation and disease. The transient receptor potential vanilloid 1 (TRPV1) is air excitatory cation channel, rather selectively expressed in a subpopulation of nociceptive, primary sensory neurons that promote neurogenic inflammation via neuropeptide release. TRPV1 is activated by noxious temperature, low extracellular pH and diverse lipid derivatives, and is uniquely sensitive to vanilloid molecules, including capsaicin. TRPV1 expression and sensitivity is highly regulated by diverse G protein-coupled and tyrosine kinase receptors. Other exogenous or endogenous chemical agents, including reactive oxygen species, ethanol and hydrogen sulphide sensitize/activate TRPV1. In the airways, TRPV1 agonists; cause cough, bronchoconstriction, microvascular leakage, hyperreactivity and hypersecretion. Patients with asthma and chronic obstructive pulmonary disease are more sensitive to the tussive effect of TRPV1 agonists and TRPV1 activation may contribute to respiratory symptoms caused by acidic media present in the airways during asthma exacerbation, gastroesophageal reflux induced asthma or in other conditions. TRPV1 antagonists may be useful in the treatment of these diseases. (c) 2005 Elsevier B.V. All rights reserved.. transient receptor potential vanilloid 1| cough| asthma exacerbation| acidic media|gene-related peptide| nerve growth-factor| obstructive pulmonary-disease| dependent protein-kinase| sensitive sensory nerves| capsaicin receptor| guinea-pig| activated receptor-2| epithelial-cells| urinary-bladder.	MAR 8-2006	transient receptor potential vanilloid 1| cough| asthma exacerbation| acidic media|gene-related peptide| nerve growth-factor| obstructive pulmonary-disease| dependent protein-kinase| sensitive sensory nerves| capsaicin receptor| guinea-pig| activated receptor-2| epithelial-cells| urinary-bladder	Geppetti, P; Materazzi, S; Nicolettl, P	The transient receptor potential vanilloid 1: Role in airway inflammation and disease		EUROPEAN JOURNAL OF PHARMACOLOGY	transient receptor potential vanilloid 1; cough; asthma exacerbation; acidic media	GENE-RELATED PEPTIDE; NERVE GROWTH-FACTOR; OBSTRUCTIVE PULMONARY-DISEASE; DEPENDENT PROTEIN-KINASE; SENSITIVE SENSORY NERVES; CAPSAICIN RECEPTOR; GUINEA-PIG; ACTIVATED RECEPTOR-2; EPITHELIAL-CELLS; URINARY-BLADDER	The transient receptor potential vanilloid 1 (TRPV1) is air excitatory cation channel, rather selectively expressed in a subpopulation of nociceptive, primary sensory neurons that promote neurogenic inflammation via neuropeptide release. TRPV1 is activated by noxious temperature, low extracellular pH and diverse lipid derivatives, and is uniquely sensitive to vanilloid molecules, including capsaicin. TRPV1 expression and sensitivity is highly regulated by diverse G protein-coupled and tyrosine kinase receptors. Other exogenous or endogenous chemical agents, including reactive oxygen species, ethanol and hydrogen sulphide sensitize/activate TRPV1. In the airways, TRPV1 agonists; cause cough, bronchoconstriction, microvascular leakage, hyperreactivity and hypersecretion. Patients with asthma and chronic obstructive pulmonary disease are more sensitive to the tussive effect of TRPV1 agonists and TRPV1 activation may contribute to respiratory symptoms caused by acidic media present in the airways during asthma exacerbation, gastroesophageal reflux induced asthma or in other conditions. TRPV1 antagonists may be useful in the treatment of these diseases. (c) 2005 Elsevier B.V. All rights reserved.	99	122	2006	8	10.1016/j.ejphar.2005.12.063	Pharmacology & Pharmacy
Is it traffic type, volume, or distance? Wheezing in infants living near truck and bus traffic. Background: Previous studies of air pollution have not examined the association between exposure to varying types, distance, and amounts of traffic and wheezing in very young infants. Objective: We sought to determine the relationship between types of traffic, traffic volume, and distance and wheezing among infants less than 1 year of age. Methods: A geographic information system and a classification scheme were developed to categorize infants enrolled in the study as living near moving truck and bus traffic (highway > 50 miles per hour, > 1000 trucks daily, < 400 m), stop-and-go truck and bus traffic (< 50 miles per hour, < 100 m), or unexposed and not residing near either. Symptom data were based on health questionnaires administered to parents when the infants were 6 months of age and monthly health diaries. Results: Infants living very near (< 100 m) stop-and-go bus and truck traffic had a significantly increased prevalence of wheezing (adjusted odds ratio, 2.50; 95% CI, 1.15-5.42) when compared with unexposed infants. The prevalence of wheezing among nonwhite infants was at least twice that of white infants, regardless of exposure. Infants living less than 400 m from a high volume of moving traffic, however, did not have an increased prevalence of wheezing. Conclusion: These results suggest that the distance from and type of traffic exposures are more significant risk factors than traffic volume for wheezing in early infancy.. diesel| traffic| truck| bus| wheezing| geographic information system| infants|diesel exhaust particles| chronic respiratory symptoms| air-pollution| bronchial hyperresponsiveness| particulate matter| cytokine production| vehicle emissions| childhood asthma| fine particles| urban air.	AUG-2005	diesel| traffic| truck| bus| wheezing| geographic information system| infants|diesel exhaust particles| chronic respiratory symptoms| air-pollution| bronchial hyperresponsiveness| particulate matter| cytokine production| vehicle emissions| childhood asthma| fine particles| urban air	Ryan, PH; LeMasters, G; Biagini, J; Bernstein, D; Grinshpun, SA; Shukla, R; Wilson, K; Villareal, M; Burkle, J; Lockey, J	Is it traffic type, volume, or distance? Wheezing in infants living near truck and bus traffic		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	diesel; traffic; truck; bus; wheezing; geographic information system; infants	DIESEL EXHAUST PARTICLES; CHRONIC RESPIRATORY SYMPTOMS; AIR-POLLUTION; BRONCHIAL HYPERRESPONSIVENESS; PARTICULATE MATTER; CYTOKINE PRODUCTION; VEHICLE EMISSIONS; CHILDHOOD ASTHMA; FINE PARTICLES; URBAN AIR	Background: Previous studies of air pollution have not examined the association between exposure to varying types, distance, and amounts of traffic and wheezing in very young infants. Objective: We sought to determine the relationship between types of traffic, traffic volume, and distance and wheezing among infants less than 1 year of age. Methods: A geographic information system and a classification scheme were developed to categorize infants enrolled in the study as living near moving truck and bus traffic (highway > 50 miles per hour, > 1000 trucks daily, < 400 m), stop-and-go truck and bus traffic (< 50 miles per hour, < 100 m), or unexposed and not residing near either. Symptom data were based on health questionnaires administered to parents when the infants were 6 months of age and monthly health diaries. Results: Infants living very near (< 100 m) stop-and-go bus and truck traffic had a significantly increased prevalence of wheezing (adjusted odds ratio, 2.50; 95% CI, 1.15-5.42) when compared with unexposed infants. The prevalence of wheezing among nonwhite infants was at least twice that of white infants, regardless of exposure. Infants living less than 400 m from a high volume of moving traffic, however, did not have an increased prevalence of wheezing. Conclusion: These results suggest that the distance from and type of traffic exposures are more significant risk factors than traffic volume for wheezing in early infancy.	45	122	2005	6	10.1016/j.jaci.2005.014	Allergy; Immunology
Association of NOD1 polymorphisms with atopic eczema and related phenotypes. Background: Interactions with microbial pathogens are crucial for the maturation of the immune system. The nucleotide-binding oligomerization domain protein 1 (NOD1) is a cytosolic receptor sensing a muropeptide found mostly in gram-negative bacterial peptidoglycans. NOD1 is located on chromosome 7p14-p15, a region that has been linked with atopy. Recently, polymorphisms of the closely related NOD2 have been associated with atopy-related traits. Objectives: Within a large population-based cohort of German adults (n = 1417), a case-control population for atopic eczema (n = 454), and a large cohort of parent-offspring trios for atopic eczema (189 trios), we evaluated 11 NOD1 polymorphisms for associations with atopic phenotypes. Methods: Subjects were phenotyped by standardized questionnaires and interviews, skin examination, and serum IgE measurements. Genotyping was performed by using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Results: Analyses revealed significant association of one NOD1 haplotype with atopic eczema in the population-based cohort (P = .004) and the case-control population (P = .003). Another NOD1 haplotype was associated with decreased total IgE (P = .008). In addition, significant associations with total serum IgE levels were observed for polymorphisms rs2907748 (P = .006), rs2907749 (P = .012), and rs2075822 (P = .018). These polymorphisms were significantly associated with atopic eczema and asthma in the family-based association analyses (P = .001-043). Seven polymorphisms showed significant transmission distortion for total IgE levels (P values < .0001-.029). Conclusion: These data indicate that genetic variants within NOD1 are important determinants of atopy susceptibility.. atopic eczema| asthma| allergic rhinoconjunctivitis| ige| card4| nod1| snp| haplotype| association|respiratory-health-survey| house-dust endotoxin| toll-like receptor-2| crohns-disease| linkage disequilibrium| hygiene hypothesis| innate immunity| celiac-disease| asthma| children.	JUL-2005	atopic eczema| asthma| allergic rhinoconjunctivitis| ige| card4| nod1| snp| haplotype| association|respiratory-health-survey| house-dust endotoxin| toll-like receptor-2| crohns-disease| linkage disequilibrium| hygiene hypothesis| innate immunity| celiac-disease| asthma| children	Weidinger, S; Klopp, N; Rummler, L; Wagenpfeil, S; Novak, N; Baurecht, HJ; Groer, W; Darsow, U; Heinrich, J; Gauger, A; Schafer, T; Jakob, T; Behrendt, H; Wichmann, HE; Ring, J; Illig, T	Association of NOD1 polymorphisms with atopic eczema and related phenotypes		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopic eczema; asthma; allergic rhinoconjunctivitis; IgE; CARD4; NOD1; SNP; haplotype; association	RESPIRATORY-HEALTH-SURVEY; HOUSE-DUST ENDOTOXIN; TOLL-LIKE RECEPTOR-2; CROHNS-DISEASE; LINKAGE DISEQUILIBRIUM; HYGIENE HYPOTHESIS; INNATE IMMUNITY; CELIAC-DISEASE; ASTHMA; CHILDREN	Background: Interactions with microbial pathogens are crucial for the maturation of the immune system. The nucleotide-binding oligomerization domain protein 1 (NOD1) is a cytosolic receptor sensing a muropeptide found mostly in gram-negative bacterial peptidoglycans. NOD1 is located on chromosome 7p14-p15, a region that has been linked with atopy. Recently, polymorphisms of the closely related NOD2 have been associated with atopy-related traits. Objectives: Within a large population-based cohort of German adults (n = 1417), a case-control population for atopic eczema (n = 454), and a large cohort of parent-offspring trios for atopic eczema (189 trios), we evaluated 11 NOD1 polymorphisms for associations with atopic phenotypes. Methods: Subjects were phenotyped by standardized questionnaires and interviews, skin examination, and serum IgE measurements. Genotyping was performed by using matrix-assisted laser desorption ionization-time of flight mass spectrometry. Results: Analyses revealed significant association of one NOD1 haplotype with atopic eczema in the population-based cohort (P = .004) and the case-control population (P = .003). Another NOD1 haplotype was associated with decreased total IgE (P = .008). In addition, significant associations with total serum IgE levels were observed for polymorphisms rs2907748 (P = .006), rs2907749 (P = .012), and rs2075822 (P = .018). These polymorphisms were significantly associated with atopic eczema and asthma in the family-based association analyses (P = .001-043). Seven polymorphisms showed significant transmission distortion for total IgE levels (P values < .0001-.029). Conclusion: These data indicate that genetic variants within NOD1 are important determinants of atopy susceptibility.	48	122	2005	8	10.1016/j.jaci.2005.02.034	Allergy; Immunology
Wheeze phenotypes and lung function in preschool children. Distinct phenotypes can be identified in childhood wheezing illness. Within the context of a birth cohort study, we investigated the association between preschool lung function and phenotypes of wheeze. From parentally reported history of wheeze (interviewer-administered questionnaire, age 3 and 5 years), children were classified as never wheezers, transient early wheezers, late-onset wheezers, or persistent wheezers. Lung function (specific airway resistance [sRaw]; kPa/second) was assessed at age 3 (n = 463) and 5 years (n = 690). Persistent wheezers had markedly poorer lung function compared with other groups. In children who had wheezed by age 3, the risk of persistent wheeze increased with increased sRaw (odds ratio [OR] 5.2, 95% confidence interval [CI] 1.3-22.0; p = 0.02). In a multivariate model, increasing sRaw (OR 5.5, 95% CI 1.2-25.9; p = 0.03) and the child's sensitization (OR 2.8, 95% CI 1.3-5.8; p = 0.008) were significant independent predictors of persistent wheezing. We found no association between lung function at age 3 and late-onset wheeze in children who had not wheezed previously (OR 0.6, 95% CI 0.07-5.3; p = 0.64). In conclusion, poor lung function at age 3 predicted the subsequent persistence of symptoms in children who had wheezed within the first 3 years, but was not associated with the onset of wheeze after age 3 in children who had not wheezed previously.. dry air challenge| lung function| specific airway resistance| wheeze phenotypes|cold-air challenge| respiratory symptoms| bronchial responsiveness| manchester asthma| healthy-children| young-children| early-life| infants| childhood| adult.	FEB 1-2005	dry air challenge| lung function| specific airway resistance| wheeze phenotypes|cold-air challenge| respiratory symptoms| bronchial responsiveness| manchester asthma| healthy-children| young-children| early-life| infants| childhood| adult	Lowe, LA; Simpson, A; Woodcock, A; Morris, J; Murray, CS; Custovic, A	Wheeze phenotypes and lung function in preschool children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	dry air challenge; lung function; specific airway resistance; wheeze phenotypes	COLD-AIR CHALLENGE; RESPIRATORY SYMPTOMS; BRONCHIAL RESPONSIVENESS; MANCHESTER ASTHMA; HEALTHY-CHILDREN; YOUNG-CHILDREN; EARLY-LIFE; INFANTS; CHILDHOOD; ADULT	Distinct phenotypes can be identified in childhood wheezing illness. Within the context of a birth cohort study, we investigated the association between preschool lung function and phenotypes of wheeze. From parentally reported history of wheeze (interviewer-administered questionnaire, age 3 and 5 years), children were classified as never wheezers, transient early wheezers, late-onset wheezers, or persistent wheezers. Lung function (specific airway resistance [sRaw]; kPa/second) was assessed at age 3 (n = 463) and 5 years (n = 690). Persistent wheezers had markedly poorer lung function compared with other groups. In children who had wheezed by age 3, the risk of persistent wheeze increased with increased sRaw (odds ratio [OR] 5.2, 95% confidence interval [CI] 1.3-22.0; p = 0.02). In a multivariate model, increasing sRaw (OR 5.5, 95% CI 1.2-25.9; p = 0.03) and the child's sensitization (OR 2.8, 95% CI 1.3-5.8; p = 0.008) were significant independent predictors of persistent wheezing. We found no association between lung function at age 3 and late-onset wheeze in children who had not wheezed previously (OR 0.6, 95% CI 0.07-5.3; p = 0.64). In conclusion, poor lung function at age 3 predicted the subsequent persistence of symptoms in children who had wheezed within the first 3 years, but was not associated with the onset of wheeze after age 3 in children who had not wheezed previously.	33	122	2005	7	10.1164/rccm.200406-695OC	General & Internal Medicine; Respiratory System
Allergy and asthma in elite summer sport athletes. Exercise may increase ventilation up to 200 L/min for short periods of time in speed and power athletes, and for longer periods in endurance athletes, such as long-distance runners and swimmers. Therefore highly trained athletes are repeatedly and strongly exposed to cold air during winter training and to many pollen allergens in spring and summer. Competitive swimmers inhale and microaspirate large amounts of air that floats above the water surface, which means exposure to chlorine derivatives from swimming pool disinfectants. In the summer Olympic Games, 4% to 15% of the athletes showed evidence of asthma or used anti-asthmatic medication. Asthma is most commonly found in endurance events, such as cycling, swimming, or long-distance running. The risk of asthma is especially increased among competitive swimmers, of which 36% to 79% show bronchial hyperresponsiveness to methacholine or histamine. The risk of asthma is closely associated with atopy and its severity among athletes. A few studies have investigated occurrence of exercise-induced bronchospasm among highly trained athletes, The occurrences of exercise-induced bronchospasm vary from 3% to 35% and depend on testing environment, type of exercise used, and athlete population tested. Mild eosinophilic airway inflammation has been shown to affect elite swimmers and cross-country skiers. This eosinophilic inflammation correlates with clinical parameters (ie, exercise-induced bronchial symptoms and bronchial hyperresponsiveness). Athletes commonly use antiasthmatic medication to treat their exercise-induced bronchial symptoms. However, controlled studies on their long-term effects on bronchial hyperresponsiveness and airway inflammation in the athletes are lacking. Follow-up studies on asthma in athletes are also lacking. What will happen to bronchial hyperresponsiveness and airway inflammation after discontinuation of competitional career is unclear. In the future, follow-up studies on bronchial responsiveness and airway inflammation, as well as controlled studies on both short- and long-term effects of antiasthmatic drugs in the athletes are needed.. asthma| athletes| bronchial hyperresponsiveness| chlorine derivatives| maximal exercise capacity| sports medicine| summer events| swimming|exercise-induced bronchospasm| cross-country skiers| cold-air| induced bronchoconstriction| bronchial responsiveness| figure skaters| mild asthma| children| exposure| swimmers.	SEP-2000	asthma| athletes| bronchial hyperresponsiveness| chlorine derivatives| maximal exercise capacity| sports medicine| summer events| swimming|exercise-induced bronchospasm| cross-country skiers| cold-air| induced bronchoconstriction| bronchial responsiveness| figure skaters| mild asthma| children| exposure| swimmers	Helenius, I; Haahtela, T	Allergy and asthma in elite summer sport athletes		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; athletes; bronchial hyperresponsiveness; chlorine derivatives; maximal exercise capacity; sports medicine; summer events; swimming	EXERCISE-INDUCED BRONCHOSPASM; CROSS-COUNTRY SKIERS; COLD-AIR; INDUCED BRONCHOCONSTRICTION; BRONCHIAL RESPONSIVENESS; FIGURE SKATERS; MILD ASTHMA; CHILDREN; EXPOSURE; SWIMMERS	Exercise may increase ventilation up to 200 L/min for short periods of time in speed and power athletes, and for longer periods in endurance athletes, such as long-distance runners and swimmers. Therefore highly trained athletes are repeatedly and strongly exposed to cold air during winter training and to many pollen allergens in spring and summer. Competitive swimmers inhale and microaspirate large amounts of air that floats above the water surface, which means exposure to chlorine derivatives from swimming pool disinfectants. In the summer Olympic Games, 4% to 15% of the athletes showed evidence of asthma or used anti-asthmatic medication. Asthma is most commonly found in endurance events, such as cycling, swimming, or long-distance running. The risk of asthma is especially increased among competitive swimmers, of which 36% to 79% show bronchial hyperresponsiveness to methacholine or histamine. The risk of asthma is closely associated with atopy and its severity among athletes. A few studies have investigated occurrence of exercise-induced bronchospasm among highly trained athletes, The occurrences of exercise-induced bronchospasm vary from 3% to 35% and depend on testing environment, type of exercise used, and athlete population tested. Mild eosinophilic airway inflammation has been shown to affect elite swimmers and cross-country skiers. This eosinophilic inflammation correlates with clinical parameters (ie, exercise-induced bronchial symptoms and bronchial hyperresponsiveness). Athletes commonly use antiasthmatic medication to treat their exercise-induced bronchial symptoms. However, controlled studies on their long-term effects on bronchial hyperresponsiveness and airway inflammation in the athletes are lacking. Follow-up studies on asthma in athletes are also lacking. What will happen to bronchial hyperresponsiveness and airway inflammation after discontinuation of competitional career is unclear. In the future, follow-up studies on bronchial responsiveness and airway inflammation, as well as controlled studies on both short- and long-term effects of antiasthmatic drugs in the athletes are needed.	63	122	2000	9	10.1067/mai.2000.107749	Allergy; Immunology
"Early infancy microbial and metabolic alterations affect risk of childhood asthma. Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a ""critical window"" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children.. longitudinal development child| nuclear-magnetic-resonance| early-life| intestinal microbiota| antibiotic exposure| allergic-asthma| gut microbiota| young-children| birth cohort| disease."	SEP 30-2015	longitudinal development child| nuclear-magnetic-resonance| early-life| intestinal microbiota| antibiotic exposure| allergic-asthma| gut microbiota| young-children| birth cohort| disease	Arrieta, MC; Stiemsma, LT; Dimitriu, PA; Thorson, L; Russell, S; Yurist-Doutsch, S; Kuzeljevic, B; Gold, MJ; Britton, HM; Lefebvre, DL; Subbarao, P; Mandhane, P; Becker, A; McNagny, KM; Sears, MR; Kollmann, T; Mohn, WW; Turvey, SE; Finlay, BB	Early infancy microbial and metabolic alterations affect risk of childhood asthma		SCIENCE TRANSLATIONAL MEDICINE		LONGITUDINAL DEVELOPMENT CHILD; NUCLEAR-MAGNETIC-RESONANCE; EARLY-LIFE; INTESTINAL MICROBIOTA; ANTIBIOTIC EXPOSURE; ALLERGIC-ASTHMA; GUT MICROBIOTA; YOUNG-CHILDREN; BIRTH COHORT; DISEASE	"Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a ""critical window"" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children."	68	121	2015	14	10.1126/scitranslmed.aab2271	Cell Biology; Research & Experimental Medicine
MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4(+) T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion. Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity.. allergic lung inflammation| dust-mite allergen| dendritic cells| in-vivo| adaptive immunity| cysteine protease| antibody-response| th2 responses| il-4| expression.	AUG 21-2014	allergic lung inflammation| dust-mite allergen| dendritic cells| in-vivo| adaptive immunity| cysteine protease| antibody-response| th2 responses| il-4| expression	Oliphant, CJ; Hwang, YY; Walker, JA; Salimi, M; Wong, SH; Brewer, JM; Englezakis, A; Barlow, JL; Hams, E; Scanlon, ST; Ogg, GS; Fallon, PG; McKenzie, ANJ	MHCII-Mediated Dialog between Group 2 Innate Lymphoid Cells and CD4(+) T Cells Potentiates Type 2 Immunity and Promotes Parasitic Helminth Expulsion		IMMUNITY		ALLERGIC LUNG INFLAMMATION; DUST-MITE ALLERGEN; DENDRITIC CELLS; IN-VIVO; ADAPTIVE IMMUNITY; CYSTEINE PROTEASE; ANTIBODY-RESPONSE; TH2 RESPONSES; IL-4; EXPRESSION	Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCII-expressing ILC2s interact with antigen-specific T cells to instigate a dialog in which IL-2 production from T cells promotes ILC2 proliferation and IL-13 production. Deletion of MHCII renders IL-13-expressing ILC2s incapable of efficiently inducing Nippostrongylus brasiliensis expulsion. Thus, during transition to adaptive T cell-mediated immunity, the ILC2 and T cell crosstalk contributes to their mutual maintenance, expansion and cytokine production. This interaction appears to augment dendritic-cell-induced T cell activation and identifies a previously unappreciated pathway in the regulation of type-2 immunity.	44	121	2014	13	10.1016/j.immuni.2014.06.016	Immunology
Chronic rhinosinusitis: Epidemiology and medical management. Chronic rhinosinusitis (CRS) affects 12.5% of the US population. On epidemiologic grounds, some association has been found between CRS prevalence and air pollution, active cigarette smoking, secondhand smoke exposure, perennial allergic rhinitis, and gastroesophageal reflux. The majority of pediatric and adult patients with CRS are immune competent. Data on genetic associations with CRS are still sparse. Current consensus definitions subclassify CRS into CRS without nasal polyposis (CRSsNP), CRS with nasal polyposis (CRSwNP), and allergic fungal rhinosinusitis (AFRS). Evaluation and medical management of CRS has been the subject of several recent consensus reports. The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics. The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations. Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP. Sinus surgery followed by use of systemic steroids is recommended for AFRS. Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled treatment trials. The various modalities of medical treatment are reviewed in the context of recent consensus documents and the author's personal experience. (J Allergy Clin Immunol 2011; 128:693-707.). rhinosinusitis| sinusitis| nasal polyposis| epidemiology| medical management| treatment|endoscopic sinus surgery| allergic fungal rhinosinusitis| placebo-controlled trial| chronic hyperplastic sinusitis| messenger-rna expression| aqueous nasal spray| quality-of-life| double-blind| aspirin desensitization| mucociliary clearance.	OCT-2011	rhinosinusitis| sinusitis| nasal polyposis| epidemiology| medical management| treatment|endoscopic sinus surgery| allergic fungal rhinosinusitis| placebo-controlled trial| chronic hyperplastic sinusitis| messenger-rna expression| aqueous nasal spray| quality-of-life| double-blind| aspirin desensitization| mucociliary clearance	Hamilos, DL	Chronic rhinosinusitis: Epidemiology and medical management		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Rhinosinusitis; sinusitis; nasal polyposis; epidemiology; medical management; treatment	ENDOSCOPIC SINUS SURGERY; ALLERGIC FUNGAL RHINOSINUSITIS; PLACEBO-CONTROLLED TRIAL; CHRONIC HYPERPLASTIC SINUSITIS; MESSENGER-RNA EXPRESSION; AQUEOUS NASAL SPRAY; QUALITY-OF-LIFE; DOUBLE-BLIND; ASPIRIN DESENSITIZATION; MUCOCILIARY CLEARANCE	Chronic rhinosinusitis (CRS) affects 12.5% of the US population. On epidemiologic grounds, some association has been found between CRS prevalence and air pollution, active cigarette smoking, secondhand smoke exposure, perennial allergic rhinitis, and gastroesophageal reflux. The majority of pediatric and adult patients with CRS are immune competent. Data on genetic associations with CRS are still sparse. Current consensus definitions subclassify CRS into CRS without nasal polyposis (CRSsNP), CRS with nasal polyposis (CRSwNP), and allergic fungal rhinosinusitis (AFRS). Evaluation and medical management of CRS has been the subject of several recent consensus reports. The highest level of evidence for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long-term macrolide antibiotics. The highest level of evidence for treatment of CRSwNP exists for intranasal steroids, systemic glucocorticoids, and topical steroid irrigations. Aspirin desensitization is beneficial for patients with aspirin-intolerant CRSwNP. Sinus surgery followed by use of systemic steroids is recommended for AFRS. Other modalities of treatment, such as antibiotics for patients with purulent infection and antifungal drugs for patients with AFRS, are potentially useful despite a lack of evidence from controlled treatment trials. The various modalities of medical treatment are reviewed in the context of recent consensus documents and the author's personal experience. (J Allergy Clin Immunol 2011; 128:693-707.)	131	121	2011	17	10.1016/j.jaci.2011.08.004	Allergy; Immunology
Orchestrating house dust mite-associated allergy in the lung. House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways disease for asthma research have recently switched from the use of surrogate allergen ovalbumin together with adjuvant to use of the HDM extract. This has accelerated understanding of how adaptive and innate immunity generate downstream pathology. We review the myriad ways in which HDM allergic responses are orchestrated. Understanding the molecular pathways that elicit HDM-associated pathology is likely to reveal novel targets for therapeutic intervention.. protease-activated receptor-2| thymic stromal lymphopoietin| adaptive immune-responses| growth-factor receptor| dendritic cells| airway inflammation| dermatophagoides-pteronyssinus| t-cell| structural biology| nlrp3 inflammasome.	SEP-2011	protease-activated receptor-2| thymic stromal lymphopoietin| adaptive immune-responses| growth-factor receptor| dendritic cells| airway inflammation| dermatophagoides-pteronyssinus| t-cell| structural biology| nlrp3 inflammasome	Gregory, LG; Lloyd, CM	Orchestrating house dust mite-associated allergy in the lung		TRENDS IN IMMUNOLOGY		PROTEASE-ACTIVATED RECEPTOR-2; THYMIC STROMAL LYMPHOPOIETIN; ADAPTIVE IMMUNE-RESPONSES; GROWTH-FACTOR RECEPTOR; DENDRITIC CELLS; AIRWAY INFLAMMATION; DERMATOPHAGOIDES-PTERONYSSINUS; T-CELL; STRUCTURAL BIOLOGY; NLRP3 INFLAMMASOME	House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways disease for asthma research have recently switched from the use of surrogate allergen ovalbumin together with adjuvant to use of the HDM extract. This has accelerated understanding of how adaptive and innate immunity generate downstream pathology. We review the myriad ways in which HDM allergic responses are orchestrated. Understanding the molecular pathways that elicit HDM-associated pathology is likely to reveal novel targets for therapeutic intervention.	104	121	2011	10	10.1016/j.it.2011.06.006	Immunology
"Interactions between Innate Antiviral and Atopic Immunoinflammatory Pathways Precipitate and Sustain Asthma Exacerbations in Children. Severe asthma exacerbations in children requiring hospitalization are typically associated with viral infection and occur almost exclusively among atopics, but the significance of these comorbidities is unknown. We hypothesized that underlying interactions between immunoinflammatory pathways related to responses to aeroallergen and virus are involved, and that evidence of these interactions is detectable in circulating cells during exacerbations. To address this hypothesis we used a genomics-based approach involving profiling of PBMC subpopulations collected during exacerbation vs convalescence by microarray and flow cytometry. We demonstrate that circulating T cells manifest the postactivated ""exhausted"" phenotype during exacerbations, whereas monocyte/dendritic cell populations display up-regulated CCR2 expression accompanied by phenotypic changes that have strong potential for enhancing local inflammation after their recruitment to the atopic lung. Notably, up-regulation of Fc epsilon R1, which is known to markedly amplify capacity for allergen uptake/presentation to Th2 effector cells via IgE-mediated allergen capture, and secondarily programming of IL-4/IL-13-dependent IL-13R(+) alternatively activated macrophages that have been demonstrated in experimental settings to be a potent source of autocrine IL-13 production. We additionally show that this disease-associated activation profile can be reproduced in vitro by cytokine exposure of atopic monocytes, and furthermore that IFN-alpha can exert both positive and negative roles in the process. Our findings suggest that respiratory viral infection in atopic children may initiate an atopy-dependent cascade that amplifies and sustains airway inflammation initiated by innate antiviral immunity via harnessing underlying atopy-associated mechanisms. These interactions may account for the unique susceptibility of atopics to severe viral-induced asthma exacerbations. The Journal of Immunology, 2009, 183: 2793-2800.. fc-epsilon-ri| allergic airway inflammation| killer t-cells| dendritic cells| respiratory-tract| viral-infection| hospital admissions| immune-response| virus-infection| expression."	AUG 15-2009	fc-epsilon-ri| allergic airway inflammation| killer t-cells| dendritic cells| respiratory-tract| viral-infection| hospital admissions| immune-response| virus-infection| expression	Subrata, LS; Bizzintino, J; Mamessier, E; Bosco, A; McKenna, KL; Wikstrom, ME; Goldblatt, J; Sly, PD; Hales, BJ; Thomas, WR; Laing, IA; LeSouef, PN; Holt, PG	Interactions between Innate Antiviral and Atopic Immunoinflammatory Pathways Precipitate and Sustain Asthma Exacerbations in Children		JOURNAL OF IMMUNOLOGY		FC-EPSILON-RI; ALLERGIC AIRWAY INFLAMMATION; KILLER T-CELLS; DENDRITIC CELLS; RESPIRATORY-TRACT; VIRAL-INFECTION; HOSPITAL ADMISSIONS; IMMUNE-RESPONSE; VIRUS-INFECTION; EXPRESSION	"Severe asthma exacerbations in children requiring hospitalization are typically associated with viral infection and occur almost exclusively among atopics, but the significance of these comorbidities is unknown. We hypothesized that underlying interactions between immunoinflammatory pathways related to responses to aeroallergen and virus are involved, and that evidence of these interactions is detectable in circulating cells during exacerbations. To address this hypothesis we used a genomics-based approach involving profiling of PBMC subpopulations collected during exacerbation vs convalescence by microarray and flow cytometry. We demonstrate that circulating T cells manifest the postactivated ""exhausted"" phenotype during exacerbations, whereas monocyte/dendritic cell populations display up-regulated CCR2 expression accompanied by phenotypic changes that have strong potential for enhancing local inflammation after their recruitment to the atopic lung. Notably, up-regulation of Fc epsilon R1, which is known to markedly amplify capacity for allergen uptake/presentation to Th2 effector cells via IgE-mediated allergen capture, and secondarily programming of IL-4/IL-13-dependent IL-13R(+) alternatively activated macrophages that have been demonstrated in experimental settings to be a potent source of autocrine IL-13 production. We additionally show that this disease-associated activation profile can be reproduced in vitro by cytokine exposure of atopic monocytes, and furthermore that IFN-alpha can exert both positive and negative roles in the process. Our findings suggest that respiratory viral infection in atopic children may initiate an atopy-dependent cascade that amplifies and sustains airway inflammation initiated by innate antiviral immunity via harnessing underlying atopy-associated mechanisms. These interactions may account for the unique susceptibility of atopics to severe viral-induced asthma exacerbations. The Journal of Immunology, 2009, 183: 2793-2800."	56	121	2009	8	10.4049/jimmunol.0900695	Immunology
"Epidemiological and immunological evidence for the hygiene hypothesis. Allergic diseases are inflammatory disorders that develop on the basis of complex gene-environment interactions. The prevalence of allergies is steadily increasing and seems to be associated with modern lifestyle. Therefore, it was hypothesized that high living standards and hygienic conditions are correlated with an increased risk for the development of an allergic disease. This so-called ""hygiene hypothesis"" states that due to reduced exposure to microbial components, the proposed allergy-preventing potential of these factors is no more present in sufficient qualities and/or quantities, which leads to an imbalance of the immune system with a predisposition to the development of allergic disorders. Meanwhile, several epidemiological studies were conducted supporting this concept and generating novel ideas for the underlying mechanisms that were then followed up by use of well-defined animal models and human studies. The current view of cellular and molecular mechanisms responsible for these phenomena includes changes in the fine balancing of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) responses which are triggered by altered or missing innate immune cell activation. In fact, proper activation of cells of the innate immune system via their so-called pattern recognition receptors has been demonstrated to play a crucial role in early shaping of the immune system and suppression of the development of Th2-driven allergic immune responses. These processes start already in utero and prenatal as well as early postnatal developmental stages seem to represent a certain ""window of opportunity"" for allergy-preventing environmental influences. (C) 2007 Elsevier GmbH. All rights reserved.. hygiene hypothesis| allergy| t cell responses| innate immunity|toll-like receptors| regulatory t-cells| pattern-recognition receptor| allergic airway disease| innate immune-system| lactic-acid bacteria| dendritic cells| murine model| intestinal microflora| atopic-dermatitis."	2007	hygiene hypothesis| allergy| t cell responses| innate immunity|toll-like receptors| regulatory t-cells| pattern-recognition receptor| allergic airway disease| innate immune-system| lactic-acid bacteria| dendritic cells| murine model| intestinal microflora| atopic-dermatitis	Garn, H; Renz, H	Epidemiological and immunological evidence for the hygiene hypothesis		IMMUNOBIOLOGY	hygiene hypothesis; allergy; T cell responses; innate immunity	TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; PATTERN-RECOGNITION RECEPTOR; ALLERGIC AIRWAY DISEASE; INNATE IMMUNE-SYSTEM; LACTIC-ACID BACTERIA; DENDRITIC CELLS; MURINE MODEL; INTESTINAL MICROFLORA; ATOPIC-DERMATITIS	"Allergic diseases are inflammatory disorders that develop on the basis of complex gene-environment interactions. The prevalence of allergies is steadily increasing and seems to be associated with modern lifestyle. Therefore, it was hypothesized that high living standards and hygienic conditions are correlated with an increased risk for the development of an allergic disease. This so-called ""hygiene hypothesis"" states that due to reduced exposure to microbial components, the proposed allergy-preventing potential of these factors is no more present in sufficient qualities and/or quantities, which leads to an imbalance of the immune system with a predisposition to the development of allergic disorders. Meanwhile, several epidemiological studies were conducted supporting this concept and generating novel ideas for the underlying mechanisms that were then followed up by use of well-defined animal models and human studies. The current view of cellular and molecular mechanisms responsible for these phenomena includes changes in the fine balancing of T helper cell 1 (Th1), Th2 and regulatory T cell (Treg) responses which are triggered by altered or missing innate immune cell activation. In fact, proper activation of cells of the innate immune system via their so-called pattern recognition receptors has been demonstrated to play a crucial role in early shaping of the immune system and suppression of the development of Th2-driven allergic immune responses. These processes start already in utero and prenatal as well as early postnatal developmental stages seem to represent a certain ""window of opportunity"" for allergy-preventing environmental influences. (C) 2007 Elsevier GmbH. All rights reserved."	98	121	2007	12	10.1016/j.imbio.2007.03.006	Immunology
Scabies: a ubiquitous neglected skin disease. Scabies has been a scourge among human beings for thousands of years. Its worldwide occurrence with epidemics during war, famine, and overcrowding is responsible for an estimated 300 million people currently infested. Scabies refers to the various skin lesions produced by female mites, and their eggs and scybala that are deposited in the epidermis, leading to delayed-type hypersensitivity reaction. Recent immunological findings such as cross-reactivity with house dust mite allergens and an altered T-helper-1/T-helper-2 pattern contribute to a better understanding of the pathomechanism. Furthermore, progress in molecular biology and cloning of relevant antigens could enable the development of a diagnostic ELISA system and candidate vaccines in the near future. Typical and atypical clinical presentations with pruritus as a hallmark of scabies occur in young, pregnant, immunocompromised, and elderly patients and include bullous and crusted (Norwegian) manifestations as well as those masked by steroid use (scabies incognito). This article reviews scabies management strategies in developed countries and resource-poor communities as well as typical complications, including the emergence of resistance and drug-related adverse events. Other problems such as post-scabies eczema and reinfestation, and newer treatments such as ivermectin are also discussed.. crusted norwegian scabies| house-dust mite| tea tree oil| sarcoptes-scabiei| dermatophagoides-pteronyssinus| oral ivermectin| in-vitro| nosocomial outbreak| northern australia| epidemic scabies.	DEC-2006	crusted norwegian scabies| house-dust mite| tea tree oil| sarcoptes-scabiei| dermatophagoides-pteronyssinus| oral ivermectin| in-vitro| nosocomial outbreak| northern australia| epidemic scabies	Hengge, UR; Currie, BJ; Jager, G; Lupi, O; Schwartz, RA	Scabies: a ubiquitous neglected skin disease		LANCET INFECTIOUS DISEASES		CRUSTED NORWEGIAN SCABIES; HOUSE-DUST MITE; TEA TREE OIL; SARCOPTES-SCABIEI; DERMATOPHAGOIDES-PTERONYSSINUS; ORAL IVERMECTIN; IN-VITRO; NOSOCOMIAL OUTBREAK; NORTHERN AUSTRALIA; EPIDEMIC SCABIES	Scabies has been a scourge among human beings for thousands of years. Its worldwide occurrence with epidemics during war, famine, and overcrowding is responsible for an estimated 300 million people currently infested. Scabies refers to the various skin lesions produced by female mites, and their eggs and scybala that are deposited in the epidermis, leading to delayed-type hypersensitivity reaction. Recent immunological findings such as cross-reactivity with house dust mite allergens and an altered T-helper-1/T-helper-2 pattern contribute to a better understanding of the pathomechanism. Furthermore, progress in molecular biology and cloning of relevant antigens could enable the development of a diagnostic ELISA system and candidate vaccines in the near future. Typical and atypical clinical presentations with pruritus as a hallmark of scabies occur in young, pregnant, immunocompromised, and elderly patients and include bullous and crusted (Norwegian) manifestations as well as those masked by steroid use (scabies incognito). This article reviews scabies management strategies in developed countries and resource-poor communities as well as typical complications, including the emergence of resistance and drug-related adverse events. Other problems such as post-scabies eczema and reinfestation, and newer treatments such as ivermectin are also discussed.	118	121	2006	11	10.1016/S1473-3099(06)70654-5	Infectious Diseases
Specific oral tolerance induction with food in children: transient or persistent effect on food allergy?. Background: The standard treatment of food allergy is elimination of the incriminated food from the diet. Specific oral tolerance induction (SOTI) seems to be a promising approach for a causal treatment; however, it is unclear whether the tolerance achieved is transient or persistent. We report on a subset of three patients of a larger ongoing study who were treated successfully with SOTI treatment, but experienced a secondary loss of tolerance after a period of allergen avoidance. Methods: The patients suffered from IgE-mediated allergy either to cow's milk (CM) (patient A) or hen's egg (HE) (patients B and C), confirmed by double-blind, placebo-controlled food challenge (DBPCFC). SOTI treatment was performed at home on a daily basis until tolerance to a maximum of 250 ml CM or 4.5 g lyophilized HE protein was achieved. The daily maintenance dose was 100 ml CM or 2.5 g HE protein. Results: Patients A, B and C reached tolerance to the maximum dose after 37, 41 and 52 weeks, respectively. According to the protocol, patients A and B performed a strict secondary elimination diet for 2 months prior to a follow-up DBPCFC after a maintenance phase of 27 and 39 weeks, respectively. Patient C discontinued treatment for 2 days after 4 weeks on the maintenance dose. Despite previous tolerance, on re-exposure to the allergen all patients experienced moderate systemic allergic reactions. Conclusions: We conclude that SOTI can induce transient tolerance in food allergy, but does not necessarily lead to its permanent abrogation. Regular allergen intake seems necessary to maintain the established tolerance.. children| food allergy| specific oral tolerance induction.	OCT-2005	children| food allergy| specific oral tolerance induction	Rolinck-Werninghaus, C; Staden, U; Mehl, A; Hamelmann, E; Beyer, K; Niggemann, B	Specific oral tolerance induction with food in children: transient or persistent effect on food allergy?		ALLERGY	children; food allergy; specific oral tolerance induction		Background: The standard treatment of food allergy is elimination of the incriminated food from the diet. Specific oral tolerance induction (SOTI) seems to be a promising approach for a causal treatment; however, it is unclear whether the tolerance achieved is transient or persistent. We report on a subset of three patients of a larger ongoing study who were treated successfully with SOTI treatment, but experienced a secondary loss of tolerance after a period of allergen avoidance. Methods: The patients suffered from IgE-mediated allergy either to cow's milk (CM) (patient A) or hen's egg (HE) (patients B and C), confirmed by double-blind, placebo-controlled food challenge (DBPCFC). SOTI treatment was performed at home on a daily basis until tolerance to a maximum of 250 ml CM or 4.5 g lyophilized HE protein was achieved. The daily maintenance dose was 100 ml CM or 2.5 g HE protein. Results: Patients A, B and C reached tolerance to the maximum dose after 37, 41 and 52 weeks, respectively. According to the protocol, patients A and B performed a strict secondary elimination diet for 2 months prior to a follow-up DBPCFC after a maintenance phase of 27 and 39 weeks, respectively. Patient C discontinued treatment for 2 days after 4 weeks on the maintenance dose. Despite previous tolerance, on re-exposure to the allergen all patients experienced moderate systemic allergic reactions. Conclusions: We conclude that SOTI can induce transient tolerance in food allergy, but does not necessarily lead to its permanent abrogation. Regular allergen intake seems necessary to maintain the established tolerance.	5	121	2005	3	10.1111/j.1398-9995.2005.00882.x	Allergy; Immunology
IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis. Background: Autoreactivity of patients with atopic dermatitis (AD) to human proteins has been postulated as a decisive pathogenetic factor for AD. Objective: In this study, it was investigated whether the stress-inducible enzyme manganese superoxide dismutase (MnSOD) of human and fungal origin might act as an autoallergen in atopic dermatitis. Methods: Patients with AD (n = 69; mean SCORAD [SCORing Atopic Dermatitis], 27) and other inflammatory skin diseases as well as with inhalant allergies were investigated. The presence of specific IgE against recombinant MnSOD of fungal and human origin and the fungal extracts of Aspergillus fumigatus and Malassezia sympodialis was measured by CAP, ELISA, skin prick test, and in subset of patients also by atopy patch tests (APTs) and PBMC proliferation assays. Cross-reactivity between allergens was determined by CAP inhibition. The presence of MnSOD in human skin in various inflammatory skin conditions was investigated by immunohistochemistry. Results: Specific IgE antibodies against human MnSOD correlating with the disease activity were found in 29 out of 67 patients with AD. The human protein was able to induce in vitro T-cell reactivity and eczematous reactions in APT in MnSOD-sensitized patients with AD. MnSOD was upregulated in various inflammatory skin reactions and APT skin specimens. Cosensitization to structurally related and cross-reacting fungal MnSOD and the skin-colonizing yeast M sympodialis was observed in all patients sensitized against human MnSOD. Conclusion: Human MnSOD may play a role as an autoallergen in a subset of patients with AD, including nonatopic eczema. By molecular mimicry leading to cross-reactivity such sensitization might be induced primarily by exposure to environmental fungal MnSOD of M sympodialis.. autoallergy| aspergillus fumigatus| atopic dermatitis| atopy| fungi| malassezia sympodialis| intrinsic type| nonatopic eczema| recombinant allergens|allergic bronchopulmonary aspergillosis| fumigatus allergens| patch test| malassezia| disease| autoantibodies| itraconazole| reactivity| responses| cloning.	MAY-2005	autoallergy| aspergillus fumigatus| atopic dermatitis| atopy| fungi| malassezia sympodialis| intrinsic type| nonatopic eczema| recombinant allergens|allergic bronchopulmonary aspergillosis| fumigatus allergens| patch test| malassezia| disease| autoantibodies| itraconazole| reactivity| responses| cloning	Schmid-Grendelmeier, P; Fluckiger, S; Disch, R; Trautmann, A; Wuthrich, B; Blaser, K; Scheynius, A; Crameri, R	IgE-mediated and T cell-mediated autoimmunity against manganese superoxide dismutase in atopic dermatitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	autoallergy; Aspergillus fumigatus; atopic dermatitis; atopy; fungi; Malassezia sympodialis; intrinsic type; nonatopic eczema; recombinant allergens	ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; FUMIGATUS ALLERGENS; PATCH TEST; MALASSEZIA; DISEASE; AUTOANTIBODIES; ITRACONAZOLE; REACTIVITY; RESPONSES; CLONING	Background: Autoreactivity of patients with atopic dermatitis (AD) to human proteins has been postulated as a decisive pathogenetic factor for AD. Objective: In this study, it was investigated whether the stress-inducible enzyme manganese superoxide dismutase (MnSOD) of human and fungal origin might act as an autoallergen in atopic dermatitis. Methods: Patients with AD (n = 69; mean SCORAD [SCORing Atopic Dermatitis], 27) and other inflammatory skin diseases as well as with inhalant allergies were investigated. The presence of specific IgE against recombinant MnSOD of fungal and human origin and the fungal extracts of Aspergillus fumigatus and Malassezia sympodialis was measured by CAP, ELISA, skin prick test, and in subset of patients also by atopy patch tests (APTs) and PBMC proliferation assays. Cross-reactivity between allergens was determined by CAP inhibition. The presence of MnSOD in human skin in various inflammatory skin conditions was investigated by immunohistochemistry. Results: Specific IgE antibodies against human MnSOD correlating with the disease activity were found in 29 out of 67 patients with AD. The human protein was able to induce in vitro T-cell reactivity and eczematous reactions in APT in MnSOD-sensitized patients with AD. MnSOD was upregulated in various inflammatory skin reactions and APT skin specimens. Cosensitization to structurally related and cross-reacting fungal MnSOD and the skin-colonizing yeast M sympodialis was observed in all patients sensitized against human MnSOD. Conclusion: Human MnSOD may play a role as an autoallergen in a subset of patients with AD, including nonatopic eczema. By molecular mimicry leading to cross-reactivity such sensitization might be induced primarily by exposure to environmental fungal MnSOD of M sympodialis.	38	121	2005	8	10.1016/j.jaci.2005.01.065	Allergy; Immunology
Polycyclic aromatic hydrocarbons, environmental tobacco smoke, and respiratory symptoms in an inner-city birth cohort. Study objectives: Several studies have found associations between diesel exposure, respiratory symptoms, and/or impaired pulmonary function. We hypothesized that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH), important components of diesel exhaust and other combustion sources, may be associated with respiratory symptoms in young children. We also hypothesized that exposure to environmental tobacco smoke (ETS) may worsen symptoms beyond that observed to be associated with PAH alone. Design/participants: To test our hypotheses, we recruited 303 pregnant women from northern Manhattan believed to be at high risk for exposure to both PAH and ETS, collected 48-h personal PAH exposure measurements, and monitored their children prospectively. Results: By 12 months of age, more cough and wheeze were reported in children exposed to prenatal PAH in concert with ETS postnatally (PAH X ETS interaction odds ratios [ORs], 1.41 [p < 0.01] and 1.29 [p < 0.05], respectively). By 24 months, difficulty breathing and probable asthma were reported more frequently among children exposed to prenatal PAH and ETS postnatally (PAR X ETS ORs, 1.54 and 1.64, respectively [p < 0.05]). Conclusions: Our results suggest that early exposure to airborne PAH and ETS can lead to increased respiratory symptoms and probable asthma by age 12 to 24 months. Interventions to lower the risk of respiratory disease in young children living in the inner city may need to address the importance of multiple environmental exposures.. asthma| environmental tobacco smoke| polycyclic aromatic hydrocarbons|diesel exhaust particles| cigarette-smoke| lung-function| air-pollution| exposure| allergen| challenge| mice| ige| particulate.	OCT-2004	asthma| environmental tobacco smoke| polycyclic aromatic hydrocarbons|diesel exhaust particles| cigarette-smoke| lung-function| air-pollution| exposure| allergen| challenge| mice| ige| particulate	Miller, RL; Garfinkel, R; Horton, M; Camann, D; Pereral, FP; Whyatt, RM; Kinney, PL	Polycyclic aromatic hydrocarbons, environmental tobacco smoke, and respiratory symptoms in an inner-city birth cohort		CHEST	asthma; environmental tobacco smoke; polycyclic aromatic hydrocarbons	DIESEL EXHAUST PARTICLES; CIGARETTE-SMOKE; LUNG-FUNCTION; AIR-POLLUTION; EXPOSURE; ALLERGEN; CHALLENGE; MICE; IGE; PARTICULATE	Study objectives: Several studies have found associations between diesel exposure, respiratory symptoms, and/or impaired pulmonary function. We hypothesized that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH), important components of diesel exhaust and other combustion sources, may be associated with respiratory symptoms in young children. We also hypothesized that exposure to environmental tobacco smoke (ETS) may worsen symptoms beyond that observed to be associated with PAH alone. Design/participants: To test our hypotheses, we recruited 303 pregnant women from northern Manhattan believed to be at high risk for exposure to both PAH and ETS, collected 48-h personal PAH exposure measurements, and monitored their children prospectively. Results: By 12 months of age, more cough and wheeze were reported in children exposed to prenatal PAH in concert with ETS postnatally (PAH X ETS interaction odds ratios [ORs], 1.41 [p < 0.01] and 1.29 [p < 0.05], respectively). By 24 months, difficulty breathing and probable asthma were reported more frequently among children exposed to prenatal PAH and ETS postnatally (PAR X ETS ORs, 1.54 and 1.64, respectively [p < 0.05]). Conclusions: Our results suggest that early exposure to airborne PAH and ETS can lead to increased respiratory symptoms and probable asthma by age 12 to 24 months. Interventions to lower the risk of respiratory disease in young children living in the inner city may need to address the importance of multiple environmental exposures.	38	121	2004	8	10.1378/chest.126.4.1071	General & Internal Medicine; Respiratory System
Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women. OBJECTIVE - Inflammation plays a key role in chronic obstructive pulmonary disease (COPD) and asthma. Increasing evidence points toward a role of inflammation in the pathogenesis of type 2 diabetes. We wanted to determine the relation of COPD and asthma with the development of type 2 diabetes. RESEARCH DESIGN AND METHODS - The Nurses' Health Study is a prospective cohort study. From 1988-1996, 103,614 female nurses were asked biennially about a physician diagnosis of emphysema, chronic bronchitis, asthma, and diabetes. RESULTS - During 8 years of follow-up, we documented a total of 2,959 new cases of type 2 diabetes. The risk of type 2 diabetes was significantly higher for patients with COPD than those without (multivariate relative risk 1.8, 95% CI 1.1-2.8). By contrast, the risk of type 2 diabetes among asthmatic patients was not increased (1.0, 0.8-1.2). The asthma results remained non-significant even when we evaluated diabetes risk by duration of asthma exposure. CONCLUSIONS - Our findings suggest that COPD may be a risk factor for developing type 2 diabetes. Differences in the inflammation and cytokine profile between COPD and asthma might explain why COPD, but not asthma, is associated with increased risk of type 2 diabetes.. tumor-necrosis-factor| c-reactive protein| insulin-resistance| oxidative stress| gene-transcription| lung-function| tnf-alpha| mellitus| weight| cohort.	OCT-2004	tumor-necrosis-factor| c-reactive protein| insulin-resistance| oxidative stress| gene-transcription| lung-function| tnf-alpha| mellitus| weight| cohort	Rana, JS; Mittleman, MA; Sheikh, J; Hu, FB; Manson, JE; Colditz, GA; Speizer, FE; Barr, RG; Camargo, CA	Chronic obstructive pulmonary disease, asthma, and risk of type 2 diabetes in women		DIABETES CARE		TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; OXIDATIVE STRESS; GENE-TRANSCRIPTION; LUNG-FUNCTION; TNF-ALPHA; MELLITUS; WEIGHT; COHORT	OBJECTIVE - Inflammation plays a key role in chronic obstructive pulmonary disease (COPD) and asthma. Increasing evidence points toward a role of inflammation in the pathogenesis of type 2 diabetes. We wanted to determine the relation of COPD and asthma with the development of type 2 diabetes. RESEARCH DESIGN AND METHODS - The Nurses' Health Study is a prospective cohort study. From 1988-1996, 103,614 female nurses were asked biennially about a physician diagnosis of emphysema, chronic bronchitis, asthma, and diabetes. RESULTS - During 8 years of follow-up, we documented a total of 2,959 new cases of type 2 diabetes. The risk of type 2 diabetes was significantly higher for patients with COPD than those without (multivariate relative risk 1.8, 95% CI 1.1-2.8). By contrast, the risk of type 2 diabetes among asthmatic patients was not increased (1.0, 0.8-1.2). The asthma results remained non-significant even when we evaluated diabetes risk by duration of asthma exposure. CONCLUSIONS - Our findings suggest that COPD may be a risk factor for developing type 2 diabetes. Differences in the inflammation and cytokine profile between COPD and asthma might explain why COPD, but not asthma, is associated with increased risk of type 2 diabetes.	47	121	2004	7	10.2337/diacare.27.10.2478	Endocrinology & Metabolism
Particle concentrations in inner-city homes of children with asthma: The effect of smoking, cooking, and outdoor pollution. inner-city children have high rates of asthma. Exposures to particles, including allergens, may cause or exacerbate asthma symptoms. As part of an epidemiologic study of inner-city children with asthma, continuous (10-min average) measurements of particle concentrations were made for 2-week periods in 294 homes drawn from seven cities. Measurements were made using an optical scattering device that is most sensitive to fine particles. The concentrations recorded by these devices were corrected to agree with colocated outdoor gravimetric PM2.5 monitors. Indoor concentrations in the homes averaged 27.7 (standard deviation = 35.9) mug/m(3), compared with concurrent outdoor concentrations of 13.6 (7.5) mug/m(3). A multivariate model indicated that outdoor particles penetrated indoors with an efficiency of 0.48 and were therefore responsible for only 25% of the mean indoor concentration. The major indoor source was smoking, which elevated indoor concentrations by 37 mug/m(3) in the 10 1 homes with smokers. Other significant sources included frying, smoky cooking events, use of incense, and apartment housing, although the increases due to these events ranged only from 3 to 6 mug/m(3). The 10-min averaging time allowed calculation of an average diurnal variation, showing large increases in the evening due to smoking and smaller increases at meal times due to cooking. Most of the observed variance in indoor concentrations was day to day, with roughly similar contributions to the variance from visit to visit and home to home within a city and only a small contribution made by variance among cities. The small variation among cities and the similarity across cities of the observed indoor air particle distributions suggest that sources of indoor concentrations do not vary considerably from one city to the next, and thus that simple models can predict indoor air concentrations in cities having only outdoor measurements.. continuous monitors| environmental tobacco smoke| gravimetric measurements| indoor air| mie pdr| optical scattering| pm10| pm2.5|particulate air-pollution| personal exposure| fine particles| hospital admissions| airborne particles| indoor| seattle| baltimore| matter| epidemiology.	JUL-2003	continuous monitors| environmental tobacco smoke| gravimetric measurements| indoor air| mie pdr| optical scattering| pm10| pm2.5|particulate air-pollution| personal exposure| fine particles| hospital admissions| airborne particles| indoor| seattle| baltimore| matter| epidemiology	Wallace, LA; Mitchell, H; O'Connor, GT; Neas, L; Lippmann, M; Kattan, M; Koenig, J; Stout, JW; Vaughn, BJ; Wallace, D; Walter, M; Adams, K; Liu, LJS	Particle concentrations in inner-city homes of children with asthma: The effect of smoking, cooking, and outdoor pollution		ENVIRONMENTAL HEALTH PERSPECTIVES	continuous monitors; environmental tobacco smoke; gravimetric measurements; indoor air; MIE pDR; optical scattering; PM10; PM2.5	PARTICULATE AIR-POLLUTION; PERSONAL EXPOSURE; FINE PARTICLES; HOSPITAL ADMISSIONS; AIRBORNE PARTICLES; INDOOR; SEATTLE; BALTIMORE; MATTER; EPIDEMIOLOGY	inner-city children have high rates of asthma. Exposures to particles, including allergens, may cause or exacerbate asthma symptoms. As part of an epidemiologic study of inner-city children with asthma, continuous (10-min average) measurements of particle concentrations were made for 2-week periods in 294 homes drawn from seven cities. Measurements were made using an optical scattering device that is most sensitive to fine particles. The concentrations recorded by these devices were corrected to agree with colocated outdoor gravimetric PM2.5 monitors. Indoor concentrations in the homes averaged 27.7 (standard deviation = 35.9) mug/m(3), compared with concurrent outdoor concentrations of 13.6 (7.5) mug/m(3). A multivariate model indicated that outdoor particles penetrated indoors with an efficiency of 0.48 and were therefore responsible for only 25% of the mean indoor concentration. The major indoor source was smoking, which elevated indoor concentrations by 37 mug/m(3) in the 10 1 homes with smokers. Other significant sources included frying, smoky cooking events, use of incense, and apartment housing, although the increases due to these events ranged only from 3 to 6 mug/m(3). The 10-min averaging time allowed calculation of an average diurnal variation, showing large increases in the evening due to smoking and smaller increases at meal times due to cooking. Most of the observed variance in indoor concentrations was day to day, with roughly similar contributions to the variance from visit to visit and home to home within a city and only a small contribution made by variance among cities. The small variation among cities and the similarity across cities of the observed indoor air particle distributions suggest that sources of indoor concentrations do not vary considerably from one city to the next, and thus that simple models can predict indoor air concentrations in cities having only outdoor measurements.	46	121	2003	8	10.1289/ehp.6135	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Exercise in elite summer athletes: Challenges for diagnosis. Background: There is a high prevalence of asthma and exercise-induced bronchoconstriction (EIB) in elite athletes when the diagnosis is based on symptoms and medication use. Objective measurements are now required by some sporting bodies to support a diagnosis of asthma or EIB to justify use of beta-agonists. Such measurements could include bronchial provocation with methacholine, with eucapnic voluntary hyperpnea (EVH) of dry air (a surrogate for exercise), or both. Objective: The aim of the study was to investigate the relationship between asthma symptoms and responses to methacholine and the EVH challenge in a group of unselected elite summer-sport athletes. The outcome would be to inform practitioners of a suitable objective approach to identifying those with asthma and EIB. Methods: Fifty elite summer-sport athletes with or without asthma were recruited from sporting teams and sports medicine centers throughout Melbourne, Australia. All subjects completed a respiratory questionnaire and, on separate days, underwent a bronchoprovocation challenge test with methacholine and EVH. Results: Forty-two subjects reported one or more respiratory symptoms in the past year, 9 had positive methacholine challenge results (mean PD20 of 1.69 +/- 2.05 mumol), and 25 had posit e EVH challenge results (mean fall in FEV1 of 25.4% +/- 15%). Although all subjects with positive methacholine challenge results had positive EVH challenge results, methacholine had a negative predictive value of only 61% and a sensitivity of 36% for identifying those responsive to EVH. Conclusion: These findings suggest that the pathogenesis of EIB in elite athletes might be different from that of asthma, and as such, neither symptoms nor the methacholine challenge test should be used exclusively for identifying EIB.. asthma| eucapnic hyperpnea| elite athletes| methacholine challenge|eucapnic voluntary hyperventilation| induced asthma| bronchial responsiveness| induced bronchospasm| hypertonic saline| reactivity| children| methacholine| provocation| salbutamol.	SEP-2002	asthma| eucapnic hyperpnea| elite athletes| methacholine challenge|eucapnic voluntary hyperventilation| induced asthma| bronchial responsiveness| induced bronchospasm| hypertonic saline| reactivity| children| methacholine| provocation| salbutamol	Holzer, K; Anderson, SD; Douglass, J	Exercise in elite summer athletes: Challenges for diagnosis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; eucapnic hyperpnea; elite athletes; methacholine challenge	EUCAPNIC VOLUNTARY HYPERVENTILATION; INDUCED ASTHMA; BRONCHIAL RESPONSIVENESS; INDUCED BRONCHOSPASM; HYPERTONIC SALINE; REACTIVITY; CHILDREN; METHACHOLINE; PROVOCATION; SALBUTAMOL	Background: There is a high prevalence of asthma and exercise-induced bronchoconstriction (EIB) in elite athletes when the diagnosis is based on symptoms and medication use. Objective measurements are now required by some sporting bodies to support a diagnosis of asthma or EIB to justify use of beta-agonists. Such measurements could include bronchial provocation with methacholine, with eucapnic voluntary hyperpnea (EVH) of dry air (a surrogate for exercise), or both. Objective: The aim of the study was to investigate the relationship between asthma symptoms and responses to methacholine and the EVH challenge in a group of unselected elite summer-sport athletes. The outcome would be to inform practitioners of a suitable objective approach to identifying those with asthma and EIB. Methods: Fifty elite summer-sport athletes with or without asthma were recruited from sporting teams and sports medicine centers throughout Melbourne, Australia. All subjects completed a respiratory questionnaire and, on separate days, underwent a bronchoprovocation challenge test with methacholine and EVH. Results: Forty-two subjects reported one or more respiratory symptoms in the past year, 9 had positive methacholine challenge results (mean PD20 of 1.69 +/- 2.05 mumol), and 25 had posit e EVH challenge results (mean fall in FEV1 of 25.4% +/- 15%). Although all subjects with positive methacholine challenge results had positive EVH challenge results, methacholine had a negative predictive value of only 61% and a sensitivity of 36% for identifying those responsive to EVH. Conclusion: These findings suggest that the pathogenesis of EIB in elite athletes might be different from that of asthma, and as such, neither symptoms nor the methacholine challenge test should be used exclusively for identifying EIB.	35	121	2002	7	10.1067/mai.2002.127784	Allergy; Immunology
Occupational asthma caused by chloramines in indoor swimming-pool air. The first series of three workers who developed occupational asthma following exposure to airborne chloramines in indoor chlorinated swimming pools is reported. Health problems of swimmers in indoor pools have traditionally been attributed to the chlorine in the water. Chlorine reacts with bodily proteins to form chloramines; the most volatile and prevalent in the air above swimming pools is nitrogen trichloride. Two lifeguards and one swimming teacher with symptoms suggestive of occupational asthma kept 2-hourly measurements of peak expiratory flow at home and at work, analysed using the occupational asthma system (OASYS) plotter, and/or had specific bronchial challenge testing to nitrogen trichloride, or a workplace challenge. Air measurement in one of the pools showed the nitrogen trichloride levels to be 0.1-0.57 mg.m(-3), which was similar to other studies. Two workers had peak expiratory flow measurements showing occupational asthma (OASYS-2 scores 2.88 and 3.8), both had a positive specific challenge to nitrogen trichloride at 0.5 mg.m(-3) with negative challenges to chlorine released from sodium hypochlorite. The third worker had a positive workplace challenge. Swimming-pool asthma due to airborne nitrogen trichloride can occur in workers who do not enter the water because of this chloramine. The air above indoor swimming pools therefore needs to be assessed and managed as carefully as the water.. bronchial provocation test| nitrogen trichloride| occupational asthma| peak expiratory flow| swimming pool|bronchial responsiveness| workers.	MAY-2002	bronchial provocation test| nitrogen trichloride| occupational asthma| peak expiratory flow| swimming pool|bronchial responsiveness| workers	Thickett, KM; McCoach, JS; Gerber, JM; Sadhra, S; Burge, PS	Occupational asthma caused by chloramines in indoor swimming-pool air		EUROPEAN RESPIRATORY JOURNAL	bronchial provocation test; nitrogen trichloride; occupational asthma; peak expiratory flow; swimming pool	BRONCHIAL RESPONSIVENESS; WORKERS	The first series of three workers who developed occupational asthma following exposure to airborne chloramines in indoor chlorinated swimming pools is reported. Health problems of swimmers in indoor pools have traditionally been attributed to the chlorine in the water. Chlorine reacts with bodily proteins to form chloramines; the most volatile and prevalent in the air above swimming pools is nitrogen trichloride. Two lifeguards and one swimming teacher with symptoms suggestive of occupational asthma kept 2-hourly measurements of peak expiratory flow at home and at work, analysed using the occupational asthma system (OASYS) plotter, and/or had specific bronchial challenge testing to nitrogen trichloride, or a workplace challenge. Air measurement in one of the pools showed the nitrogen trichloride levels to be 0.1-0.57 mg.m(-3), which was similar to other studies. Two workers had peak expiratory flow measurements showing occupational asthma (OASYS-2 scores 2.88 and 3.8), both had a positive specific challenge to nitrogen trichloride at 0.5 mg.m(-3) with negative challenges to chlorine released from sodium hypochlorite. The third worker had a positive workplace challenge. Swimming-pool asthma due to airborne nitrogen trichloride can occur in workers who do not enter the water because of this chloramine. The air above indoor swimming pools therefore needs to be assessed and managed as carefully as the water.	12	121	2002	6	10.1183/09031936.02.00232802	Respiratory System
Occupational seafood allergy: a review. Background-Recent years have seen increased levels of production and consumption of seafood, leading to more frequent reporting of allergic reactions in occupational and domestic settings. This review focuses on occupational allergy in the fishing and seafood processing industry. Review-Workers involved in either manual or automated processing of crabs' prawns, mussels, fish, and fishmeal production are commonly exposed to various constituents of seafood. Aerosolisation of seafood and cooking fluid during processing are potential occupational situations that could result in sensitisation through inhalation. There is great variability of aerosol exposure within and among various jobs with reported allergen concentrations ranging from 0.001 to 5.061(mug/m(3)). Occupational dermal exposure occurs as a result of unprotected handling of seafood and its byproducts. Occupational allergies have been reported in workers exposed to arthropods (crustaceans), molluscs, pisces (bony fish) and other agents derived from seafood. The prevalence of occupational asthma ranges from 7% to 36%, and for occupational protein contact dermatitis, from 3% to 11%. These health outcomes are mainly due to high molecular weight proteins in seafood causing an IgE mediated response. Cross reactivity between various species within a major seafood grouping also occurs. Limited evidence from dose-response relations indicate that development of symptoms is related to duration or intensity of exposure. The evidence for atopy as a risk factor for occupational sensitisation and asthma is supportive, whereas evidence for cigarette smoking is limited. Disruption of the intact skin barrier seems to be an important added risk factor for occupational protein contact dermatitis. Conclusion-The range of allergic disease associated with occupational exposure to crab is well characterised, whereas for other seafood agents the evidence is somewhat limited. There is a need for further epidemiological studies to better characterise this risk. More detailed characterisation of specific protein antigens in aerosols and associated establishment of dose-response relations for acute and chronic exposure to seafood; the respective roles of skin contact and inhalational exposure in allergic sensitisation and cross reactivity; and the contribution of host associated factors in the development of occupational seafood allergies are important areas for future research.. occupational seafood allergy| occupational asthma| protein contact dermatitis|protein contact-dermatitis| fish processing-industry| human epidermal keratin| hypersensitivity reactions| respiratory symptoms| urticaria syndrome| skin temperature| major allergen| ige| asthma.	SEP-2001	occupational seafood allergy| occupational asthma| protein contact dermatitis|protein contact-dermatitis| fish processing-industry| human epidermal keratin| hypersensitivity reactions| respiratory symptoms| urticaria syndrome| skin temperature| major allergen| ige| asthma	Jeebhay, MF; Robins, TG; Lehrer, SB; Lopata, AL	Occupational seafood allergy: a review		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE	occupational seafood allergy; occupational asthma; protein contact dermatitis	PROTEIN CONTACT-DERMATITIS; FISH PROCESSING-INDUSTRY; HUMAN EPIDERMAL KERATIN; HYPERSENSITIVITY REACTIONS; RESPIRATORY SYMPTOMS; URTICARIA SYNDROME; SKIN TEMPERATURE; MAJOR ALLERGEN; IGE; ASTHMA	Background-Recent years have seen increased levels of production and consumption of seafood, leading to more frequent reporting of allergic reactions in occupational and domestic settings. This review focuses on occupational allergy in the fishing and seafood processing industry. Review-Workers involved in either manual or automated processing of crabs' prawns, mussels, fish, and fishmeal production are commonly exposed to various constituents of seafood. Aerosolisation of seafood and cooking fluid during processing are potential occupational situations that could result in sensitisation through inhalation. There is great variability of aerosol exposure within and among various jobs with reported allergen concentrations ranging from 0.001 to 5.061(mug/m(3)). Occupational dermal exposure occurs as a result of unprotected handling of seafood and its byproducts. Occupational allergies have been reported in workers exposed to arthropods (crustaceans), molluscs, pisces (bony fish) and other agents derived from seafood. The prevalence of occupational asthma ranges from 7% to 36%, and for occupational protein contact dermatitis, from 3% to 11%. These health outcomes are mainly due to high molecular weight proteins in seafood causing an IgE mediated response. Cross reactivity between various species within a major seafood grouping also occurs. Limited evidence from dose-response relations indicate that development of symptoms is related to duration or intensity of exposure. The evidence for atopy as a risk factor for occupational sensitisation and asthma is supportive, whereas evidence for cigarette smoking is limited. Disruption of the intact skin barrier seems to be an important added risk factor for occupational protein contact dermatitis. Conclusion-The range of allergic disease associated with occupational exposure to crab is well characterised, whereas for other seafood agents the evidence is somewhat limited. There is a need for further epidemiological studies to better characterise this risk. More detailed characterisation of specific protein antigens in aerosols and associated establishment of dose-response relations for acute and chronic exposure to seafood; the respective roles of skin contact and inhalational exposure in allergic sensitisation and cross reactivity; and the contribution of host associated factors in the development of occupational seafood allergies are important areas for future research.	108	121	2001	10	10.1136/oem.58.9.553	Public, Environmental & Occupational Health
Diesel exhaust enhances airway responsiveness in asthmatic subjects. Particulate matter (PM) pollution has been associated with negative health effects, including exacerbations of asthma following exposure to PM peaks. The aim of the present study was to investigate the effects of short-term exposure to diesel exhaust (DE) in asthmatics, by specifically addressing the effects on airway hyperresponsiveness, lung function and airway inflammation. Fourteen nonsmoking, atopic asthmatics with stable disease, on continuous treatment with inhaled corticosteroids, were included. All were hyperresponsive to methacholine. Each subject was exposed to DE (particles with a 50% cut-off aerodynamic diameter of 10 mum (PM10) 300 mug(.)m(-3)) and air during Ih on two separate occasions. Lung function was measured before and immediately after the exposures. Sputum induction was performed 6 h, and methacholine inhalation test 24 h, after each exposure. Exposure to DE was associated with a significant increase in the degree of hyperresponsiveness, as compared to after air, of 0.97 doubling concentrations at 24 h after exposure (p < 0.001). DE also induced a significant increase in airway resistance (p = 0.004) and in sputum levels of interleukin (IL)-6 (p = 0.048). No changes were detected in sputum levels of methyl-histamine, eosinophil cationic protein, myeloperoxidase and IL-8. This study indicated that short-term exposure to diesel exhaust, equal to high ambient levels of particulate matter, is associated with adverse effects in asthmatic airways, even in the presence of inhaled corticosteroid therapy. The increase in airway responsiveness may provide an important link to epidemiological findings exacerbations of asthma following exposure to particulate matter.. asthma| airway responsiveness| diesel exhaust| induced sputum|emergency room visits| induced sputum| nitrogen-dioxide| daily mortality| pollution| exposure| particles| inflammation| mice| children.	MAY-2001	asthma| airway responsiveness| diesel exhaust| induced sputum|emergency room visits| induced sputum| nitrogen-dioxide| daily mortality| pollution| exposure| particles| inflammation| mice| children	Nordenhall, C; Pourazar, J; Ledin, MC; Levin, JO; Sandstrom, T; Adelroth, E	Diesel exhaust enhances airway responsiveness in asthmatic subjects		EUROPEAN RESPIRATORY JOURNAL	asthma; airway responsiveness; diesel exhaust; induced sputum	EMERGENCY ROOM VISITS; INDUCED SPUTUM; NITROGEN-DIOXIDE; DAILY MORTALITY; POLLUTION; EXPOSURE; PARTICLES; INFLAMMATION; MICE; CHILDREN	Particulate matter (PM) pollution has been associated with negative health effects, including exacerbations of asthma following exposure to PM peaks. The aim of the present study was to investigate the effects of short-term exposure to diesel exhaust (DE) in asthmatics, by specifically addressing the effects on airway hyperresponsiveness, lung function and airway inflammation. Fourteen nonsmoking, atopic asthmatics with stable disease, on continuous treatment with inhaled corticosteroids, were included. All were hyperresponsive to methacholine. Each subject was exposed to DE (particles with a 50% cut-off aerodynamic diameter of 10 mum (PM10) 300 mug(.)m(-3)) and air during Ih on two separate occasions. Lung function was measured before and immediately after the exposures. Sputum induction was performed 6 h, and methacholine inhalation test 24 h, after each exposure. Exposure to DE was associated with a significant increase in the degree of hyperresponsiveness, as compared to after air, of 0.97 doubling concentrations at 24 h after exposure (p < 0.001). DE also induced a significant increase in airway resistance (p = 0.004) and in sputum levels of interleukin (IL)-6 (p = 0.048). No changes were detected in sputum levels of methyl-histamine, eosinophil cationic protein, myeloperoxidase and IL-8. This study indicated that short-term exposure to diesel exhaust, equal to high ambient levels of particulate matter, is associated with adverse effects in asthmatic airways, even in the presence of inhaled corticosteroid therapy. The increase in airway responsiveness may provide an important link to epidemiological findings exacerbations of asthma following exposure to particulate matter.	33	121	2001	7	10.1183/09031936.01.17509090	Respiratory System
Inhaled particulate matter causes expression of nuclear factor (NF)-kappa B-related genes and oxidant-dependent NF-kappa B activation in vitro. High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM), Brief inhalation of PM2.5 (particles of an aerodynamic diameter of <2.5 microns) (300 mu g/m(3) air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant (P less than or equal to 0.05) increases in steady-state messenger RNA (mRNA) levels of a number of nuclear factor (NF)-kappa B-associated and/or -regulated genes, including tumor necrosis factor-alpha and -beta, interleukin-6, interferon-gamma, and transforming growth factor-beta. Lung mRNA levels of lymphotoxin-beta and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NF-kappa B-luciferase reporter cell line, exposure to PM2.5 at noncytotoxic concentrations resulted in increases in transcriptional activation of NF-kappa B-dependent gene expression which were inhibited in the presence of catalase. Early and persistent increases in intracellular oxidants, as measured by flow cytometry and cell imaging using the oxidant probe 2'-7'-dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM2.5, and ultrafine carbon black particles. Studies here are the first to show NF-kappa B-related inflammatory and cytokine gene expression after inhalation of PM2.5 and oxidant-dependent induction of NF-kappa B activity by PM2.5 in pulmonary epithelial cells.. necrosis-factor-alpha| tracheal epithelial-cells| dna-binding activity| air-pollution| alveolar macrophages| rat lung| c-jun| asbestos| asthma| generation.	AUG-2000	necrosis-factor-alpha| tracheal epithelial-cells| dna-binding activity| air-pollution| alveolar macrophages| rat lung| c-jun| asbestos| asthma| generation	Shukla, A; Timblin, C; BeruBe, K; Gordon, T; McKinney, W; Driscoll, K; Vacek, P; Mossman, BT	Inhaled particulate matter causes expression of nuclear factor (NF)-kappa B-related genes and oxidant-dependent NF-kappa B activation in vitro		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		NECROSIS-FACTOR-ALPHA; TRACHEAL EPITHELIAL-CELLS; DNA-BINDING ACTIVITY; AIR-POLLUTION; ALVEOLAR MACROPHAGES; RAT LUNG; C-JUN; ASBESTOS; ASTHMA; GENERATION	High levels of ambient air pollution are associated with exacerbation of asthma and respiratory morbidity, yet little is known concerning the mechanisms of inflammation and toxicity by components of inhaled particulate matter (PM), Brief inhalation of PM2.5 (particles of an aerodynamic diameter of <2.5 microns) (300 mu g/m(3) air for 6 h followed by a period of 24 h in clean air) by either C3H/HeJ or C57/BL6 mice caused significant (P less than or equal to 0.05) increases in steady-state messenger RNA (mRNA) levels of a number of nuclear factor (NF)-kappa B-associated and/or -regulated genes, including tumor necrosis factor-alpha and -beta, interleukin-6, interferon-gamma, and transforming growth factor-beta. Lung mRNA levels of lymphotoxin-beta and macrophage migration inhibitory factor were unchanged. In murine C10 alveolar cells and an NF-kappa B-luciferase reporter cell line, exposure to PM2.5 at noncytotoxic concentrations resulted in increases in transcriptional activation of NF-kappa B-dependent gene expression which were inhibited in the presence of catalase. Early and persistent increases in intracellular oxidants, as measured by flow cytometry and cell imaging using the oxidant probe 2'-7'-dichlorofluoroscin diacetate, were observed in epithelial cells exposed to PM2.5, and ultrafine carbon black particles. Studies here are the first to show NF-kappa B-related inflammatory and cytokine gene expression after inhalation of PM2.5 and oxidant-dependent induction of NF-kappa B activity by PM2.5 in pulmonary epithelial cells.	33	121	2000	6		Biochemistry & Molecular Biology; Cell Biology; Respiratory System
A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants. Background: The prevalence of asthma has increased in developed countries in the past 2 decades. The effectiveness of intervention measures on the primary prevention of asthma has not been well studied. Objective: To assess the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants (in this study, infants are defined as persons from birth to the age of 1 year). Design: Prospective, prenatally randomized, controlled study with follow-up through the age of 1 year. Setting: University hospital-based settings at 2 Canadian centers: Vancouver, British Columbia, and Winnipeg, Manitoba. Participants: A total of 545 high-risk infants (at least 1 first-degree relative with asthma or 2 first-degree relatives with other IgE-mediated allergic diseases) identified before birth. Interventions: Avoidance of house dust mite and pet allergens and environmental tobacco smoke, encouragement of breastfeeding, and supplementation with a partially hydrolyzed formula. Main Outcome Measures: Probable or possible asthma, rhinitis without apparent colds, and a prick skin test result positive for common inhalant allergens. Results: Thirty-eight (15.1%) of the 251 infants available for assessment in the intervention group and 49 (20.2%) of the 242 infants available for assessment in the control group fulfilled the criteria for possible or probable asthma (adjusted relative risk, 0.66; 90% confidence interval, 0.44-0.98). Also, 16.7% of the infants in the intervention group and 27.3% of the infants in the control group developed rhinitis without colds (adjusted relative risk, 0.51; 90% confidence interval, 0.35-0.74). The incidence of positive skin test results to 1 or more inhalant allergens was similar in both groups (4.4% in the intervention group and 4.6% in the control group). Conclusions: Our multifaceted intervention program resulted in a modest but significant (P = .04) reduction in the risk of possible or probable asthma and rhinitis without apparent colds at the age of 12 months in high-risk infants. In the absence of a validated definition of asthma at the age of 12 months, follow-up studies are needed to determine the effectiveness of the intervention program in the primary prevention of asthma in high-risk infants.. allergen avoidance| follow-up| age| mite| diet| life.	JUL-2000	allergen avoidance| follow-up| age| mite| diet| life	Chan-Yeung, M; Manfreda, J; Dimich-Ward, H; Ferguson, A; Watson, W; Becker, A	A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		ALLERGEN AVOIDANCE; FOLLOW-UP; AGE; MITE; DIET; LIFE	Background: The prevalence of asthma has increased in developed countries in the past 2 decades. The effectiveness of intervention measures on the primary prevention of asthma has not been well studied. Objective: To assess the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants (in this study, infants are defined as persons from birth to the age of 1 year). Design: Prospective, prenatally randomized, controlled study with follow-up through the age of 1 year. Setting: University hospital-based settings at 2 Canadian centers: Vancouver, British Columbia, and Winnipeg, Manitoba. Participants: A total of 545 high-risk infants (at least 1 first-degree relative with asthma or 2 first-degree relatives with other IgE-mediated allergic diseases) identified before birth. Interventions: Avoidance of house dust mite and pet allergens and environmental tobacco smoke, encouragement of breastfeeding, and supplementation with a partially hydrolyzed formula. Main Outcome Measures: Probable or possible asthma, rhinitis without apparent colds, and a prick skin test result positive for common inhalant allergens. Results: Thirty-eight (15.1%) of the 251 infants available for assessment in the intervention group and 49 (20.2%) of the 242 infants available for assessment in the control group fulfilled the criteria for possible or probable asthma (adjusted relative risk, 0.66; 90% confidence interval, 0.44-0.98). Also, 16.7% of the infants in the intervention group and 27.3% of the infants in the control group developed rhinitis without colds (adjusted relative risk, 0.51; 90% confidence interval, 0.35-0.74). The incidence of positive skin test results to 1 or more inhalant allergens was similar in both groups (4.4% in the intervention group and 4.6% in the control group). Conclusions: Our multifaceted intervention program resulted in a modest but significant (P = .04) reduction in the risk of possible or probable asthma and rhinitis without apparent colds at the age of 12 months in high-risk infants. In the absence of a validated definition of asthma at the age of 12 months, follow-up studies are needed to determine the effectiveness of the intervention program in the primary prevention of asthma in high-risk infants.	24	121	2000	7		Pediatrics
Mechanisms of chemical-induced innate immunity in allergic contact dermatitis. Allergic contact dermatitis (ACD) is one of the most prevalent occupational skin diseases and causes severe and long-lasting health problems in the case of chronification. It is initiated by an innate inflammatory immune response to skin contact with low molecular weight chemicals that results in the priming of chemical-specific, skin-homing CD8(+) Tc1/Tc17 and CD4(+) Th1/Th17 cells. Following this sensitization step, T lymphocytes infiltrate the inflamed skin upon challenge with the same chemical. The T cells then exert cytotoxic function and secrete inflammatory mediators to produce an eczematous skin reaction. The recent characterization of the mechanisms underlying the innate inflammatory response has revealed that contact allergens activate innate effector mechanisms and signalling pathways that are also involved in anti-infectious immunity. This emerging analogy implies infection as a potential trigger or amplifier of the sensitization to contact allergens. Moreover, new mechanistic insights into the induction of ACD identify potential targets for preventive and therapeutic intervention. We summarize here the latest findings in this area of research.. contact dermatitis| inflammation| innate immunity| nod-like receptor| toll-like receptor|nf-kappa-b| toll-like receptors| cell-line thp-1| lymph-node assay| cd8 t-cells| in-vitro| reactive oxygen| dendritic cells| skin sensitizers| gene-expression.	SEP-2011	contact dermatitis| inflammation| innate immunity| nod-like receptor| toll-like receptor|nf-kappa-b| toll-like receptors| cell-line thp-1| lymph-node assay| cd8 t-cells| in-vitro| reactive oxygen| dendritic cells| skin sensitizers| gene-expression	Martin, SF; Esser, PR; Weber, FC; Jakob, T; Freudenberg, MA; Schmidt, M; Goebeler, M	Mechanisms of chemical-induced innate immunity in allergic contact dermatitis		ALLERGY	contact dermatitis; inflammation; innate immunity; NOD-like receptor; Toll-like receptor	NF-KAPPA-B; TOLL-LIKE RECEPTORS; CELL-LINE THP-1; LYMPH-NODE ASSAY; CD8 T-CELLS; IN-VITRO; REACTIVE OXYGEN; DENDRITIC CELLS; SKIN SENSITIZERS; GENE-EXPRESSION	Allergic contact dermatitis (ACD) is one of the most prevalent occupational skin diseases and causes severe and long-lasting health problems in the case of chronification. It is initiated by an innate inflammatory immune response to skin contact with low molecular weight chemicals that results in the priming of chemical-specific, skin-homing CD8(+) Tc1/Tc17 and CD4(+) Th1/Th17 cells. Following this sensitization step, T lymphocytes infiltrate the inflamed skin upon challenge with the same chemical. The T cells then exert cytotoxic function and secrete inflammatory mediators to produce an eczematous skin reaction. The recent characterization of the mechanisms underlying the innate inflammatory response has revealed that contact allergens activate innate effector mechanisms and signalling pathways that are also involved in anti-infectious immunity. This emerging analogy implies infection as a potential trigger or amplifier of the sensitization to contact allergens. Moreover, new mechanistic insights into the induction of ACD identify potential targets for preventive and therapeutic intervention. We summarize here the latest findings in this area of research.	124	120	2011	12	10.1111/j.1398-9995.2011.02652.x	Allergy; Immunology
Respiratory disease associated with solid biomass fuel exposure in rural women and children: systematic review and meta-analysis. Background Numerous studies with varying associations between domestic use of solid biomass fuels (wood, dung, crop residue, charcoal) and respiratory diseases have been reported. Objective To present the current data systematically associating use of biomass fuels with respiratory outcomes in rural women and children. Methods Systematic searches were conducted in 13 electronic databases. Data were abstracted from original articles that satisfied selection criteria for meta-analyses. Publication bias and heterogeneity of samples were tested. Studies with common diagnoses were analysed using random-effect models. Results A total of 2717 studies were identified. Fifty-one studies were selected for data extraction and 25 studies were suitable for meta-analysis. The overall pooled ORs indicate significant associations with acute respiratory infection in children (OR 3.53, 95% CI 1.94 to 6.43), chronic bronchitis in women (OR 2.52, 95% CI 1.88 to 3.38) and chronic obstructive pulmonary disease in women (OR 2.40, 95% CI 1.47 to 3.93). In contrast, no significant association with asthma in children or women was noted. Conclusion Biomass fuel exposure is associated with diverse respiratory diseases in rural populations. Concerted efforts in improving stove design and lowering exposure to smoke emission may reduce respiratory disease associated with biomass fuel exposure.. indoor air-pollution| chronic-bronchitis| risk-factors| developing-countries| pulmonary-disease| indian children| lung-function| health| smoke| infections.	MAR-2011	indoor air-pollution| chronic-bronchitis| risk-factors| developing-countries| pulmonary-disease| indian children| lung-function| health| smoke| infections	Po, JYT; FitzGerald, JM; Carlsten, C	Respiratory disease associated with solid biomass fuel exposure in rural women and children: systematic review and meta-analysis		THORAX		INDOOR AIR-POLLUTION; CHRONIC-BRONCHITIS; RISK-FACTORS; DEVELOPING-COUNTRIES; PULMONARY-DISEASE; INDIAN CHILDREN; LUNG-FUNCTION; HEALTH; SMOKE; INFECTIONS	Background Numerous studies with varying associations between domestic use of solid biomass fuels (wood, dung, crop residue, charcoal) and respiratory diseases have been reported. Objective To present the current data systematically associating use of biomass fuels with respiratory outcomes in rural women and children. Methods Systematic searches were conducted in 13 electronic databases. Data were abstracted from original articles that satisfied selection criteria for meta-analyses. Publication bias and heterogeneity of samples were tested. Studies with common diagnoses were analysed using random-effect models. Results A total of 2717 studies were identified. Fifty-one studies were selected for data extraction and 25 studies were suitable for meta-analysis. The overall pooled ORs indicate significant associations with acute respiratory infection in children (OR 3.53, 95% CI 1.94 to 6.43), chronic bronchitis in women (OR 2.52, 95% CI 1.88 to 3.38) and chronic obstructive pulmonary disease in women (OR 2.40, 95% CI 1.47 to 3.93). In contrast, no significant association with asthma in children or women was noted. Conclusion Biomass fuel exposure is associated with diverse respiratory diseases in rural populations. Concerted efforts in improving stove design and lowering exposure to smoke emission may reduce respiratory disease associated with biomass fuel exposure.	47	120	2011	8	10.1136/thx.2010.147884	Respiratory System
The epidemiology of hand eczema in the general population - prevalence and main findings. Numerous studies have investigated the prevalence and risk factors of hand eczema in the general population. These studies are of high value as they tend to be less biased than studies using clinical populations and as they are important for healthcare decision makers when they allocate resources. This study aimed to review the epidemiology of hand eczema in the general population. Literature was examined using Pubmed-Medline, Biosis, Science Citation Index, and dermatology text books. On the basis of studies performed between 1964 and 2007, the point prevalence of hand eczema was around 4%, the 1-year prevalence nearly 10%, whereas the lifetime prevalence reached 15%. Based on seven studies, the median incidence rate of hand eczema was 5.5 cases/1000 person-years (women = 9.6 and men = 4.0). A high incidence rate was associated with female sex, contact allergy, atopic dermatitis, and wet work. Atopic dermatitis was the single most important risk factor for hand eczema. Hand eczema resulted in medical consultations in 70%, sick leave (> 7 days) in about 20%, and job change in about 10%. Mean sick time was longer among those with allergic hand eczema than those with atopic and irritant hand eczema. Moderate to severe extension of hand eczema was the strongest risk factor for persistence of hand eczema. Other risk factors included early onset of hand eczema and childhood eczema. The aetiology of hand eczema is multifactorial and includes environmental as well as genetic factors. Future studies should focus on unresolved areas of hand eczema, for example, genetic predisposition.. general population| hand eczema| hand dermatitis| nickel allergy| public health| regulation|irritant contact-dermatitis| odense adolescence cohort| secondary-school pupils| 15-year follow-up| nickel allergy| atopic-dermatitis| industrial-city| skin exposure| filaggrin mutations| swedish population.	2010	general population| hand eczema| hand dermatitis| nickel allergy| public health| regulation|irritant contact-dermatitis| odense adolescence cohort| secondary-school pupils| 15-year follow-up| nickel allergy| atopic-dermatitis| industrial-city| skin exposure| filaggrin mutations| swedish population	Thyssen, JP; Johansen, JD; Linneberg, A; Menne, T	The epidemiology of hand eczema in the general population - prevalence and main findings		CONTACT DERMATITIS	general population; hand eczema; hand dermatitis; nickel allergy; public health; regulation	IRRITANT CONTACT-DERMATITIS; ODENSE ADOLESCENCE COHORT; SECONDARY-SCHOOL PUPILS; 15-YEAR FOLLOW-UP; NICKEL ALLERGY; ATOPIC-DERMATITIS; INDUSTRIAL-CITY; SKIN EXPOSURE; FILAGGRIN MUTATIONS; SWEDISH POPULATION	Numerous studies have investigated the prevalence and risk factors of hand eczema in the general population. These studies are of high value as they tend to be less biased than studies using clinical populations and as they are important for healthcare decision makers when they allocate resources. This study aimed to review the epidemiology of hand eczema in the general population. Literature was examined using Pubmed-Medline, Biosis, Science Citation Index, and dermatology text books. On the basis of studies performed between 1964 and 2007, the point prevalence of hand eczema was around 4%, the 1-year prevalence nearly 10%, whereas the lifetime prevalence reached 15%. Based on seven studies, the median incidence rate of hand eczema was 5.5 cases/1000 person-years (women = 9.6 and men = 4.0). A high incidence rate was associated with female sex, contact allergy, atopic dermatitis, and wet work. Atopic dermatitis was the single most important risk factor for hand eczema. Hand eczema resulted in medical consultations in 70%, sick leave (> 7 days) in about 20%, and job change in about 10%. Mean sick time was longer among those with allergic hand eczema than those with atopic and irritant hand eczema. Moderate to severe extension of hand eczema was the strongest risk factor for persistence of hand eczema. Other risk factors included early onset of hand eczema and childhood eczema. The aetiology of hand eczema is multifactorial and includes environmental as well as genetic factors. Future studies should focus on unresolved areas of hand eczema, for example, genetic predisposition.	92	120	2010	13		Allergy; Dermatology
A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model. The most common technique employed to describe pulmonary gas exchange of nitric oxide (NO) combines multiple constant flow exhalations with a two-compartment model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit volume) of the airway tree and 2) gas phase axial diffusion of NO. However, recent evidence suggests that these features of the lungs are important determinants of NO exchange. The goal of this study is to present an algorithm that characterizes NO exchange using multiple constant flow exhalations and a model that considers the trumpet shape of the airway tree and axial diffusion (model TMAD). Solution of the diffusion equation for the TMAD for exhalation flows > 100 ml/s can be reduced to the same linear relationship between the NO elimination rate and the flow; however, the interpretation of the slope and the intercept depend on the model. We tested the TMAD in healthy subjects (n = 8) using commonly used and easily performed exhalation flows (100, 150, 200, and 250 ml/s). Compared with the 2CM, estimates (mean +/- SD) from the TMAD for the maximum airway flux are statistically higher (J'aw(NO) = 770 +/- 470 compared with 440 +/- 270 pl/s), whereas estimates for the steady-state alveolar concentration are statistically lower (CA(NO) = 0.66 +/- 0.98 compared with 1.2 +/- 0.80 parts/billion). Furthermore, CANO from the TMAD is not different from zero. We conclude that proximal (airways) NO production is larger than previously predicted with the 2CM and that peripheral (respiratory bronchioles and alveoli) NO is near zero in healthy subjects.. model| airway| alveolar|respiratory-tract| exhaled air| breath-hold| asthma| alveolar| impact| dynamics| humans| lungs| no.	JAN-2007	model| airway| alveolar|respiratory-tract| exhaled air| breath-hold| asthma| alveolar| impact| dynamics| humans| lungs| no	Condorelli, P; Shin, HW; Aledia, AS; Silkoff, PE; George, SC	A simple technique to characterize proximal and peripheral nitric oxide exchange using constant flow exhalations and an axial diffusion model		JOURNAL OF APPLIED PHYSIOLOGY	model; airway; alveolar	RESPIRATORY-TRACT; EXHALED AIR; BREATH-HOLD; ASTHMA; ALVEOLAR; IMPACT; DYNAMICS; HUMANS; LUNGS; NO	The most common technique employed to describe pulmonary gas exchange of nitric oxide (NO) combines multiple constant flow exhalations with a two-compartment model (2CM) that neglects 1) the trumpet shape (increasing surface area per unit volume) of the airway tree and 2) gas phase axial diffusion of NO. However, recent evidence suggests that these features of the lungs are important determinants of NO exchange. The goal of this study is to present an algorithm that characterizes NO exchange using multiple constant flow exhalations and a model that considers the trumpet shape of the airway tree and axial diffusion (model TMAD). Solution of the diffusion equation for the TMAD for exhalation flows > 100 ml/s can be reduced to the same linear relationship between the NO elimination rate and the flow; however, the interpretation of the slope and the intercept depend on the model. We tested the TMAD in healthy subjects (n = 8) using commonly used and easily performed exhalation flows (100, 150, 200, and 250 ml/s). Compared with the 2CM, estimates (mean +/- SD) from the TMAD for the maximum airway flux are statistically higher (J'aw(NO) = 770 +/- 470 compared with 440 +/- 270 pl/s), whereas estimates for the steady-state alveolar concentration are statistically lower (CA(NO) = 0.66 +/- 0.98 compared with 1.2 +/- 0.80 parts/billion). Furthermore, CANO from the TMAD is not different from zero. We conclude that proximal (airways) NO production is larger than previously predicted with the 2CM and that peripheral (respiratory bronchioles and alveoli) NO is near zero in healthy subjects.	36	120	2007	9	10.1152/japplphysiol.00533.2006	Physiology; Sport Sciences
Comparison of early and late toxic effects of sulfur mustard in Iranian veterans. Sulfur mustard is an alkylating agent that reacts with ocular, respiratory, cutaneous, and bone marrow tissues, resulting in early and late toxic effects. We compare these effects based on the experience in Iranian veterans exposed to the agent during the Iran-Iraq conflict (1983-88). The first clinical manifestations of sulfur mustard poisoning occurred in the eyes with a sensation of grittiness, lacrimation, photophobia, blepharospasm, and corneal ulceration. Respiratory effects appeared as rhinorhea, laryngitis, tracheobronchitis, and dyspnoea. Skin lesions varied from erythema to bullous necrotization. Initial leukocytosis and lymphopenia returned to normal within four weeks in recovered patients, but marked cytopenia with bone marrow failure occurred in fatal cases. Late toxic effects of sulfur mustard were most commonly found in lungs, skin and eyes. Main respiratory complications were chronic obstructive pulmonary disease, bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis. Late skin lesions were hyperpigmentation, dry skin, atrophy, and hypopigmentation. Fifteen of the severely intoxicated patients were diagnosed with delayed keratitis, having corneal vascularization, thinning, and epithelial defect. Respiratory complications exacerbated over time, while cutaneous and ocular lesions decreased or remained constant. Both the severity and frequency of bronchiectatic lesions increased during long-term follow-up. The only deteriorating cutaneous complication was dry skin. The maximum incidence of delayed kaeratitis was observed 15 to 20 years after initial exposure. Being suggested as the main cause ofassociated with malignancies and recurrent infections, natural killer cells were significantly lower 16 to 20 years after intoxication.. chemical warfare agents| respiratory-tract| gas inhalation| complications| exposure| injury| weapons| workers| cancer.	OCT-2006	chemical warfare agents| respiratory-tract| gas inhalation| complications| exposure| injury| weapons| workers| cancer	Balali-Mood, M; Hefazi, M	Comparison of early and late toxic effects of sulfur mustard in Iranian veterans		BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY		CHEMICAL WARFARE AGENTS; RESPIRATORY-TRACT; GAS INHALATION; COMPLICATIONS; EXPOSURE; INJURY; WEAPONS; WORKERS; CANCER	Sulfur mustard is an alkylating agent that reacts with ocular, respiratory, cutaneous, and bone marrow tissues, resulting in early and late toxic effects. We compare these effects based on the experience in Iranian veterans exposed to the agent during the Iran-Iraq conflict (1983-88). The first clinical manifestations of sulfur mustard poisoning occurred in the eyes with a sensation of grittiness, lacrimation, photophobia, blepharospasm, and corneal ulceration. Respiratory effects appeared as rhinorhea, laryngitis, tracheobronchitis, and dyspnoea. Skin lesions varied from erythema to bullous necrotization. Initial leukocytosis and lymphopenia returned to normal within four weeks in recovered patients, but marked cytopenia with bone marrow failure occurred in fatal cases. Late toxic effects of sulfur mustard were most commonly found in lungs, skin and eyes. Main respiratory complications were chronic obstructive pulmonary disease, bronchiectasis, asthma, large airway narrowing, and pulmonary fibrosis. Late skin lesions were hyperpigmentation, dry skin, atrophy, and hypopigmentation. Fifteen of the severely intoxicated patients were diagnosed with delayed keratitis, having corneal vascularization, thinning, and epithelial defect. Respiratory complications exacerbated over time, while cutaneous and ocular lesions decreased or remained constant. Both the severity and frequency of bronchiectatic lesions increased during long-term follow-up. The only deteriorating cutaneous complication was dry skin. The maximum incidence of delayed kaeratitis was observed 15 to 20 years after initial exposure. Being suggested as the main cause ofassociated with malignancies and recurrent infections, natural killer cells were significantly lower 16 to 20 years after intoxication.	77	120	2006	10	10.1111/j.1742-7843.2006.pto_429.x	Pharmacology & Pharmacy; Toxicology
Ambient air pollution: Health hazards to children. Ambient (outdoor) air pollution is now recognized as an important problem, both nationally and worldwide. Our scientific understanding of the spectrum of health effects of air pollution has increased, and numerous studies are finding important health effects from air pollution at levels once considered safe. Children and infants are among the most susceptible to many of the air pollutants. In addition to associations between air pollution and respiratory symptoms, asthma exacerbations, and asthma hospitalizations, recent studies have found links between air pollution and preterm birth, infant mortality, deficits in lung growth, and possibly, development of asthma. This policy statement summarizes the recent literature linking ambient air pollution to adverse health outcomes in children and includes a perspective on the current regulatory process. The statement provides advice to pediatricians on how to integrate issues regarding air quality and health into patient education and children's environmental health advocacy and concludes with recommendations to the government on promotion of effective air-pollution policies to ensure protection of children's health.. air pollution| adverse effects| children| asthma| environmental health|low-birth-weight| southern california children| respiratory hospital admissions| african-american children| diesel exhaust particles| motor-vehicle exhaust| emergency-room visits| lung-function growth| pulmonary-function| daily mortality.	DEC-2004	air pollution| adverse effects| children| asthma| environmental health|low-birth-weight| southern california children| respiratory hospital admissions| african-american children| diesel exhaust particles| motor-vehicle exhaust| emergency-room visits| lung-function growth| pulmonary-function| daily mortality	Shannon, MW; Best, D; Binns, HJ; Johnson, CL; Kim, JJ; Mazur, LJ; Reynolds, DW; Roberts, JR; Weil, WB; Balk, SJ; Miller, M; Shea, KM; Lipsett, M; Johnson, RH; Linet, M; Rogan, W; Spire, P	Ambient air pollution: Health hazards to children		PEDIATRICS	air pollution; adverse effects; children; asthma; environmental health	LOW-BIRTH-WEIGHT; SOUTHERN CALIFORNIA CHILDREN; RESPIRATORY HOSPITAL ADMISSIONS; AFRICAN-AMERICAN CHILDREN; DIESEL EXHAUST PARTICLES; MOTOR-VEHICLE EXHAUST; EMERGENCY-ROOM VISITS; LUNG-FUNCTION GROWTH; PULMONARY-FUNCTION; DAILY MORTALITY	Ambient (outdoor) air pollution is now recognized as an important problem, both nationally and worldwide. Our scientific understanding of the spectrum of health effects of air pollution has increased, and numerous studies are finding important health effects from air pollution at levels once considered safe. Children and infants are among the most susceptible to many of the air pollutants. In addition to associations between air pollution and respiratory symptoms, asthma exacerbations, and asthma hospitalizations, recent studies have found links between air pollution and preterm birth, infant mortality, deficits in lung growth, and possibly, development of asthma. This policy statement summarizes the recent literature linking ambient air pollution to adverse health outcomes in children and includes a perspective on the current regulatory process. The statement provides advice to pediatricians on how to integrate issues regarding air quality and health into patient education and children's environmental health advocacy and concludes with recommendations to the government on promotion of effective air-pollution policies to ensure protection of children's health.	98	120	2004	9	10.1542/peds.2004-2166	Pediatrics
Responses to ozone are increased in obese mice. Epidemiological data indicate an increased incidence of asthma in overweight adults and children. Ozone (O-3) is a common trigger for asthma. Accordingly, the purpose of this study was to compare O-3-induced airway hyperresponsiveness and airway inflammation in lean, wild-type (C57BL/6J) mice and mice that are obese as a consequence of a genetic defect in the gene encoding the satiety hormone leptin (ob/ob mice). The ob/ob mice eat excessively and weighed more than twice as much as age- and gender-matched wild-type mice. Airway responsiveness to intravenous methacholine was measured by forced oscillation. In air-exposed controls, baseline pulmonary resistance was greater, and the dose of methacholine required to double pulmonary resistance was lower in ob/ob than wild-type mice. Exposure to O-3 (2 parts/million for 3 h) caused AHR and airway inflammation in both groups of mice, but responses to O-3 were enhanced in ob/ob compared with wild-type mice. Administration of exogenous leptin did not reverse the enhanced inflammatory response observed in ob/ob mice, but augmented airway inflammation in wild-type mice. The inhaled dose of O-3 per gram of lung tissue was greater in ob/ob than wild-type mice. Our results indicate that O-3-induced airway responses are enhanced in ob/ob mice and suggest that inhaled O-3 dose may be one factor contributing to this difference, but other aspects of the obese phenotype may also contribute. Our results also indicate that the hormone leptin, which is increased in the obese, has the capacity to increase airway inflammation.. inflammation| polymorphonuclear leukocytes| pulmonary mechanics| leptin|tumor-necrosis-factor| body-mass index| induced airway hyperresponsiveness| emergency room visits| insulin-resistance| weight-reduction| oxidative stress| leptin receptor| factor-alpha| asthma.	SEP-2003	inflammation| polymorphonuclear leukocytes| pulmonary mechanics| leptin|tumor-necrosis-factor| body-mass index| induced airway hyperresponsiveness| emergency room visits| insulin-resistance| weight-reduction| oxidative stress| leptin receptor| factor-alpha| asthma	Shore, SA; Rivera-Sanchez, YM; Schwartzman, IN; Johnston, RA	Responses to ozone are increased in obese mice		JOURNAL OF APPLIED PHYSIOLOGY	inflammation; polymorphonuclear leukocytes; pulmonary mechanics; leptin	TUMOR-NECROSIS-FACTOR; BODY-MASS INDEX; INDUCED AIRWAY HYPERRESPONSIVENESS; EMERGENCY ROOM VISITS; INSULIN-RESISTANCE; WEIGHT-REDUCTION; OXIDATIVE STRESS; LEPTIN RECEPTOR; FACTOR-ALPHA; ASTHMA	Epidemiological data indicate an increased incidence of asthma in overweight adults and children. Ozone (O-3) is a common trigger for asthma. Accordingly, the purpose of this study was to compare O-3-induced airway hyperresponsiveness and airway inflammation in lean, wild-type (C57BL/6J) mice and mice that are obese as a consequence of a genetic defect in the gene encoding the satiety hormone leptin (ob/ob mice). The ob/ob mice eat excessively and weighed more than twice as much as age- and gender-matched wild-type mice. Airway responsiveness to intravenous methacholine was measured by forced oscillation. In air-exposed controls, baseline pulmonary resistance was greater, and the dose of methacholine required to double pulmonary resistance was lower in ob/ob than wild-type mice. Exposure to O-3 (2 parts/million for 3 h) caused AHR and airway inflammation in both groups of mice, but responses to O-3 were enhanced in ob/ob compared with wild-type mice. Administration of exogenous leptin did not reverse the enhanced inflammatory response observed in ob/ob mice, but augmented airway inflammation in wild-type mice. The inhaled dose of O-3 per gram of lung tissue was greater in ob/ob than wild-type mice. Our results indicate that O-3-induced airway responses are enhanced in ob/ob mice and suggest that inhaled O-3 dose may be one factor contributing to this difference, but other aspects of the obese phenotype may also contribute. Our results also indicate that the hormone leptin, which is increased in the obese, has the capacity to increase airway inflammation.	61	120	2003	8	10.1152/japplphysiol.00336.2003	Physiology; Sport Sciences
Exposure assessment of particulate matter for susceptible populations in Seattle. In this article we present results from a 2-year comprehensive exposure assessment study that examined the particulate matter (PM) exposures and health effects in 108 individuals with and without chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), and asthma. The average personal exposures to PM with aerodynamic diameters < 2.5 mum (PM2.5) were similar to the average outdoor PM2.5 concentrations but significantly higher than the average indoor concentrations. Personal PM2.5 exposures in our study groups were lower than those reported in other panel studies of susceptible populations. Indoor and outdoor PM2.5, PM10 (PM with aerodynamic diameters < 10 mum), and the ratio of PM2.5 to PM10 were significantly higher during the heating season. The increase in outdoor PM10 in winter was primarily due to an increase in the PM2.5 fraction. A similar seasonal variation was found for personal PM2.5. The high-risk subjects in our study engaged in an equal amount of dust-generating activities compared with the healthy elderly subjects. The children in the study experienced the highest indoor PM2.5 and PM10 concentrations. Personal PM2.5 exposures varied by study group, with elderly healthy and CHD subjects having the lowest exposures and asthmatic children having the highest exposures. Within study groups, the PM2.5 exposure varied depending on residence because of different particle infiltration efficiencies. Although we found a wide range of longitudinal correlations between central-site and personal PM2.5 measurements, the longitudinal r is closely related to the particle infiltration efficiency. PM2.5 exposures among the COPD and CHD subjects can be predicted with relatively good power with a microenvironmental model composed of three microenvironments. The prediction power is the lowest for the asthmatic children.. asthma| chd| copd| infiltration efficiency| longitudinal correlation| personal cloud| pm2.5| wood smoke|obstructive pulmonary-disease| personal exposure| air-pollution| outdoor concentrations| fine particles| epidemiology-exposure| coarse particles| case-crossover| indoor| ambient.	JUN-2003	asthma| chd| copd| infiltration efficiency| longitudinal correlation| personal cloud| pm2.5| wood smoke|obstructive pulmonary-disease| personal exposure| air-pollution| outdoor concentrations| fine particles| epidemiology-exposure| coarse particles| case-crossover| indoor| ambient	Liu, LJS; Box, M; Kalman, D; Kaufman, J; Koenig, J; Larson, T; Lumley, T; Sheppard, L; Wallace, L	Exposure assessment of particulate matter for susceptible populations in Seattle		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; CHD; COPD; infiltration efficiency; longitudinal correlation; personal cloud; PM2.5; wood smoke	OBSTRUCTIVE PULMONARY-DISEASE; PERSONAL EXPOSURE; AIR-POLLUTION; OUTDOOR CONCENTRATIONS; FINE PARTICLES; EPIDEMIOLOGY-EXPOSURE; COARSE PARTICLES; CASE-CROSSOVER; INDOOR; AMBIENT	In this article we present results from a 2-year comprehensive exposure assessment study that examined the particulate matter (PM) exposures and health effects in 108 individuals with and without chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), and asthma. The average personal exposures to PM with aerodynamic diameters < 2.5 mum (PM2.5) were similar to the average outdoor PM2.5 concentrations but significantly higher than the average indoor concentrations. Personal PM2.5 exposures in our study groups were lower than those reported in other panel studies of susceptible populations. Indoor and outdoor PM2.5, PM10 (PM with aerodynamic diameters < 10 mum), and the ratio of PM2.5 to PM10 were significantly higher during the heating season. The increase in outdoor PM10 in winter was primarily due to an increase in the PM2.5 fraction. A similar seasonal variation was found for personal PM2.5. The high-risk subjects in our study engaged in an equal amount of dust-generating activities compared with the healthy elderly subjects. The children in the study experienced the highest indoor PM2.5 and PM10 concentrations. Personal PM2.5 exposures varied by study group, with elderly healthy and CHD subjects having the lowest exposures and asthmatic children having the highest exposures. Within study groups, the PM2.5 exposure varied depending on residence because of different particle infiltration efficiencies. Although we found a wide range of longitudinal correlations between central-site and personal PM2.5 measurements, the longitudinal r is closely related to the particle infiltration efficiency. PM2.5 exposures among the COPD and CHD subjects can be predicted with relatively good power with a microenvironmental model composed of three microenvironments. The prediction power is the lowest for the asthmatic children.	48	120	2003	10	10.1289/ehp.6011	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation. We investigated the specific role of matrix metalloproteinase (MMP)-9 in allergic asthma using a murine model of allergen-induced airway inflammation and airway hyperresponsiveness in MMP-9(-/-) mice and their corresponding wild-type (WT) littermates. After a single intraperitoneal sensitization to ovalbumin, the mice were exposed daily either to ovalbumin (1%) or phosphate-buffered saline aerosols from days 14 to 21. Significantly less peribronchial mononuclear cell infiltration of the airways and less lymphocytes in the bronchoalveolar lavage fluid were detected in challenged MMP-9(-/-) as compared to WT mice. In contrast, comparable numbers of bronchoalveolar lavage fluid eosinophils; were observed in both genotypes. After allergen exposure, the WT mice developed a significant airway hyperresponsiveness to carbachol whereas the MMP-9(-/-) mice failed to do so. Allergen exposure induced an increase of MMP-9-related gelatinolytic activity in WT lung extracts. Quantitative reverse transcriptase-polymerase chain reaction showed increased mRNA levels of MMP-12, MMP-14, and urokinase-type plasminogen activator after allergen exposure in the lung extracts of WT mice but not in MMP-9-deficient mice. in contrast, the expression of tissue inhibitor of metalloproteinases-1 was enhanced after allergen exposure in both groups. We conclude that MMP-9 plays a key role in the development of airway inflammation after allergenexposure.. brown-norway rats| gelatinase-b| tissue inhibitor| bronchoalveolar lavage| endothelial-cells| human-neutrophils| mast-cells| t-cell| asthma| activation.	AUG-2002	brown-norway rats| gelatinase-b| tissue inhibitor| bronchoalveolar lavage| endothelial-cells| human-neutrophils| mast-cells| t-cell| asthma| activation	Cataldo, DD; Tournoy, KG; Vermaelen, K; Munaut, C; Foidart, JM; Louis, R; Noel, A; Pauwels, RA	Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation		AMERICAN JOURNAL OF PATHOLOGY		BROWN-NORWAY RATS; GELATINASE-B; TISSUE INHIBITOR; BRONCHOALVEOLAR LAVAGE; ENDOTHELIAL-CELLS; HUMAN-NEUTROPHILS; MAST-CELLS; T-CELL; ASTHMA; ACTIVATION	We investigated the specific role of matrix metalloproteinase (MMP)-9 in allergic asthma using a murine model of allergen-induced airway inflammation and airway hyperresponsiveness in MMP-9(-/-) mice and their corresponding wild-type (WT) littermates. After a single intraperitoneal sensitization to ovalbumin, the mice were exposed daily either to ovalbumin (1%) or phosphate-buffered saline aerosols from days 14 to 21. Significantly less peribronchial mononuclear cell infiltration of the airways and less lymphocytes in the bronchoalveolar lavage fluid were detected in challenged MMP-9(-/-) as compared to WT mice. In contrast, comparable numbers of bronchoalveolar lavage fluid eosinophils; were observed in both genotypes. After allergen exposure, the WT mice developed a significant airway hyperresponsiveness to carbachol whereas the MMP-9(-/-) mice failed to do so. Allergen exposure induced an increase of MMP-9-related gelatinolytic activity in WT lung extracts. Quantitative reverse transcriptase-polymerase chain reaction showed increased mRNA levels of MMP-12, MMP-14, and urokinase-type plasminogen activator after allergen exposure in the lung extracts of WT mice but not in MMP-9-deficient mice. in contrast, the expression of tissue inhibitor of metalloproteinases-1 was enhanced after allergen exposure in both groups. We conclude that MMP-9 plays a key role in the development of airway inflammation after allergenexposure.	50	120	2002	8	10.1016/S0002-9440(10)64205-8	Pathology
Decrease in nickel sensitization in a Danish schoolgirl population with ears pierced after implementation of a nickel-exposure regulation. Background To reduce the skin nickel exposure of the population the Danish Ministry of Environment issued a regulation that was implemented in 1992, and the European Union countries have recently adopted an expanded regulation. Objectives The aim of our combined patch testing and questionnaire investigation of girls in public schools and high schools/production schools was to evaluate whether the regulation has had an impact on the prevalence of nickel sensitization. Methods To find a group of girls with cars pierced mainly after implementation of the nickel-exposure regulation in Denmark, girls were recruited from the fifth and sixth grade in 12 public schools (the public school group). After the public school level almost all girls from a public school population continue their education in high schools or other schools such as production schools or technical schools. Therefore, to find girls demographically similar to the public school girls but older, and with ears pierced before implementation of the regulation, girls from seven high schools and two production schools were recruited (the high school group). Four hundred and twenty-seven girls in the public school group (mean age 12.4 years, range 10-14) and 534 in the high school group (mean age 18.8 years, range 17-22) participated. All participants filled out a questionnaire concerning ear piercing, use of oral braces and former patch testing for nickel sensitivity. Three hundred and five girls (71.4%) in the public school group and 275 (51.5%) in the high school group were patch tested or had been tested previously and the results of these tests were included in the study. The relation between the frequency of nickel sensitization and the various factors that might influence the prevalence of nickel sensitization was evaluated by multivariate logistic regression analysis. The investigation was conducted from March 1999 to March 2000. Results The study showed that both increasing age and having ears pierced before 1992 enhanced the prevalence of nickel sensitization. We found that 17.1% of the girls in the high school group demonstrated a positive patch test reaction to nickel. In contrast, the prevalence of nickel sensitization in the public school group was only 3.9%. Comparing girls with and without pierced ears, the prevalence of nickel sensitization was significantly higher in girls with ears pierced before, but not after, 1992 (odds ratio 3.34 and 1.20, respectively). Only in the high school group was there a tendency that wearing oral braces before ear piercing had a protective effect on nickel sensitization, but this did not reach statistical significance. Conclusions As we found an effect of ear piercing before but not after 1992, this study strongly suggests that implementation of the nickel-exposure regulation in 1992 in Denmark has had the intended effect of protecting the female population from becoming allergic to nickel.. contact allergy| denmark| exposure regulation| nickel| patch test|orthodontic treatment| immune tolerance| allergy| contact| induction| denmark| atopy.	APR-2002	contact allergy| denmark| exposure regulation| nickel| patch test|orthodontic treatment| immune tolerance| allergy| contact| induction| denmark| atopy	Jensen, CS; Lisby, S; Baadsgaard, O; Volund, A; Menne, T	Decrease in nickel sensitization in a Danish schoolgirl population with ears pierced after implementation of a nickel-exposure regulation		BRITISH JOURNAL OF DERMATOLOGY	contact allergy; Denmark; exposure regulation; nickel; patch test	ORTHODONTIC TREATMENT; IMMUNE TOLERANCE; ALLERGY; CONTACT; INDUCTION; DENMARK; ATOPY	Background To reduce the skin nickel exposure of the population the Danish Ministry of Environment issued a regulation that was implemented in 1992, and the European Union countries have recently adopted an expanded regulation. Objectives The aim of our combined patch testing and questionnaire investigation of girls in public schools and high schools/production schools was to evaluate whether the regulation has had an impact on the prevalence of nickel sensitization. Methods To find a group of girls with cars pierced mainly after implementation of the nickel-exposure regulation in Denmark, girls were recruited from the fifth and sixth grade in 12 public schools (the public school group). After the public school level almost all girls from a public school population continue their education in high schools or other schools such as production schools or technical schools. Therefore, to find girls demographically similar to the public school girls but older, and with ears pierced before implementation of the regulation, girls from seven high schools and two production schools were recruited (the high school group). Four hundred and twenty-seven girls in the public school group (mean age 12.4 years, range 10-14) and 534 in the high school group (mean age 18.8 years, range 17-22) participated. All participants filled out a questionnaire concerning ear piercing, use of oral braces and former patch testing for nickel sensitivity. Three hundred and five girls (71.4%) in the public school group and 275 (51.5%) in the high school group were patch tested or had been tested previously and the results of these tests were included in the study. The relation between the frequency of nickel sensitization and the various factors that might influence the prevalence of nickel sensitization was evaluated by multivariate logistic regression analysis. The investigation was conducted from March 1999 to March 2000. Results The study showed that both increasing age and having ears pierced before 1992 enhanced the prevalence of nickel sensitization. We found that 17.1% of the girls in the high school group demonstrated a positive patch test reaction to nickel. In contrast, the prevalence of nickel sensitization in the public school group was only 3.9%. Comparing girls with and without pierced ears, the prevalence of nickel sensitization was significantly higher in girls with ears pierced before, but not after, 1992 (odds ratio 3.34 and 1.20, respectively). Only in the high school group was there a tendency that wearing oral braces before ear piercing had a protective effect on nickel sensitization, but this did not reach statistical significance. Conclusions As we found an effect of ear piercing before but not after 1992, this study strongly suggests that implementation of the nickel-exposure regulation in 1992 in Denmark has had the intended effect of protecting the female population from becoming allergic to nickel.	25	120	2002	7	10.1046/j.1365-2133.2002.04666.x	Dermatology
The effect of air pollution on inner-city children with asthma. The effect of daily ambient air pollution was examined within a cohort of 846 asthmatic children residing in eight urban areas of the USA, using data from the National Cooperative Inner-City, Asthma Study. Daily air pollution concentrations were extracted from the Aerometric Information Retrieval System database from the Environment Protection Agency in the USA. Mixed linear models and generalized estimating equation models were used to evaluate the effects of several air pollutants (ozone, sulphur dioxide (SOD, nitrogen dioxide (NO2) and particles with a 50% cut-off aerodynamic diameter of 10 mum (PM10) on peak expiratory flow rate (PEFR) and symptoms in 846 children with a history of asthma (ages 4-9 yrs). None of the pollutants were associated with evening PEFR or symptom reports. Only ozone was associated with declines in morning %, PEFR (0.59% decline (95%, confidence interval (CI) 0.13-1.05%,) per interquartile range (IQR) increase in 5-day average ozone). In single pollutant models, each pollutant was associated with an increased incidence of morning symptoms: (odds ratio (OR)=1.16 (95%, Cl 1.02-1.30) per IQR increase in 4-day average ozone, OR=1.32 (95% CI 1.03-1.70) per IQR increase in 2-day average SO2, OR=1.48 (95% CI 1.02-2.16) per IQR increase in 6-day average NO2 and OR=1.26 (95% CI 1.0 1.59) per IQR increase in 2-day average PM10. This longitudinal analysis supports previous time-series findings that at levels below current USA air-quality standards, summer-air pollution is significantly related to symptoms and decreased pulmonary function among children with asthma.. air pollution| asthma| generalized estimating equations| inner-city| mixed linear models|respiratory-function| ambient ozone| mexico-city| particulate| association| reanalysis| responses| health.	APR-2002	air pollution| asthma| generalized estimating equations| inner-city| mixed linear models|respiratory-function| ambient ozone| mexico-city| particulate| association| reanalysis| responses| health	Mortimer, KM; Neas, LM; Dockery, DW; Redline, S; Tager, IB	The effect of air pollution on inner-city children with asthma		EUROPEAN RESPIRATORY JOURNAL	air pollution; asthma; generalized estimating equations; inner-city; mixed linear models	RESPIRATORY-FUNCTION; AMBIENT OZONE; MEXICO-CITY; PARTICULATE; ASSOCIATION; REANALYSIS; RESPONSES; HEALTH	The effect of daily ambient air pollution was examined within a cohort of 846 asthmatic children residing in eight urban areas of the USA, using data from the National Cooperative Inner-City, Asthma Study. Daily air pollution concentrations were extracted from the Aerometric Information Retrieval System database from the Environment Protection Agency in the USA. Mixed linear models and generalized estimating equation models were used to evaluate the effects of several air pollutants (ozone, sulphur dioxide (SOD, nitrogen dioxide (NO2) and particles with a 50% cut-off aerodynamic diameter of 10 mum (PM10) on peak expiratory flow rate (PEFR) and symptoms in 846 children with a history of asthma (ages 4-9 yrs). None of the pollutants were associated with evening PEFR or symptom reports. Only ozone was associated with declines in morning %, PEFR (0.59% decline (95%, confidence interval (CI) 0.13-1.05%,) per interquartile range (IQR) increase in 5-day average ozone). In single pollutant models, each pollutant was associated with an increased incidence of morning symptoms: (odds ratio (OR)=1.16 (95%, Cl 1.02-1.30) per IQR increase in 4-day average ozone, OR=1.32 (95% CI 1.03-1.70) per IQR increase in 2-day average SO2, OR=1.48 (95% CI 1.02-2.16) per IQR increase in 6-day average NO2 and OR=1.26 (95% CI 1.0 1.59) per IQR increase in 2-day average PM10. This longitudinal analysis supports previous time-series findings that at levels below current USA air-quality standards, summer-air pollution is significantly related to symptoms and decreased pulmonary function among children with asthma.	30	120	2002	7	10.1183/09031936.02.00247102	Respiratory System
Identification of population subgroups of children and adolescents with high asthma prevalence - Findings from the Third National Health and Nutrition Examination Survey. Objectives: To provide national estimates of asthma prevalence in African-American, Mexican American and white (non-Latino) children and adolescents using several common definitions; to evaluate familial, sociodemographic, and environmental risk factors that are independently associated with current asthma in children and to identify subgroups at particular risk for current asthma using 2 complementary data analytic approaches. Design: Cross-sectional study, using the Third National Health and Nutrition Examination Survey, 1988-1994. Setting: Eighty-nine mobile examination centers in the United States. Participants: Twelve thousand three hundred eighty-eight African American, Mexican American, and white (non-Latino) children and adolescents, aged 2 months through 16 years, selected from a systematic random, population-based, nationally representative sample. Main Outcome Measure: Current asthma, defined by caregivers who reported that their child currently had doctor-diagnosed asthma. Results: The overall prevalence of current asthma was 6.7% (95% confidence interval [CI], 5.6-7.8). Odds ratios for current asthma from the multiple regression analysis were 4.00 (95% CI, 2.90-5.52) for children with a parental history of asthma or hay fever, 1.94 (95% CI, 1.09-3.46) for children with body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than or equal to the 85th percentile, and 1.64 (95% CI, 1.20-2.26) for children of African American ethnicity. African American and Mexican American children showed a consistent prevalence of current asthma across age while white children showed an increase in prevalence with age. The 2 highest-risk subgroups identified by the signal detection analysis were composed of children with a parental history of asthma or hay fever who were 10 years or older with a body mass index greater than or equal to the 85th percentile (31.0% current asthma), and children with a parental history who were 10 years or younger and of African American ethnicity (15.6% current asthma). Conclusions: The findings from this analysis show a strong independent association between obesity and current asthma in children and adolescents, and confirm previous reports of a parental history of asthma or hay fever and African American ethnicity as additional important risk factors.. body-mass index| childhood asthma| united-states| risk-factors| respiratory illness| parental smoking| puerto-rican| environmental exposures| passive smoking| young-adults.	MAR-2002	body-mass index| childhood asthma| united-states| risk-factors| respiratory illness| parental smoking| puerto-rican| environmental exposures| passive smoking| young-adults	Rodriguez, MA; Winkleby, MA; Ahn, D; Sundquist, J; Kraemer, HC	Identification of population subgroups of children and adolescents with high asthma prevalence - Findings from the Third National Health and Nutrition Examination Survey		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		BODY-MASS INDEX; CHILDHOOD ASTHMA; UNITED-STATES; RISK-FACTORS; RESPIRATORY ILLNESS; PARENTAL SMOKING; PUERTO-RICAN; ENVIRONMENTAL EXPOSURES; PASSIVE SMOKING; YOUNG-ADULTS	Objectives: To provide national estimates of asthma prevalence in African-American, Mexican American and white (non-Latino) children and adolescents using several common definitions; to evaluate familial, sociodemographic, and environmental risk factors that are independently associated with current asthma in children and to identify subgroups at particular risk for current asthma using 2 complementary data analytic approaches. Design: Cross-sectional study, using the Third National Health and Nutrition Examination Survey, 1988-1994. Setting: Eighty-nine mobile examination centers in the United States. Participants: Twelve thousand three hundred eighty-eight African American, Mexican American, and white (non-Latino) children and adolescents, aged 2 months through 16 years, selected from a systematic random, population-based, nationally representative sample. Main Outcome Measure: Current asthma, defined by caregivers who reported that their child currently had doctor-diagnosed asthma. Results: The overall prevalence of current asthma was 6.7% (95% confidence interval [CI], 5.6-7.8). Odds ratios for current asthma from the multiple regression analysis were 4.00 (95% CI, 2.90-5.52) for children with a parental history of asthma or hay fever, 1.94 (95% CI, 1.09-3.46) for children with body mass index (calculated as weight in kilograms divided by the square of height in meters) greater than or equal to the 85th percentile, and 1.64 (95% CI, 1.20-2.26) for children of African American ethnicity. African American and Mexican American children showed a consistent prevalence of current asthma across age while white children showed an increase in prevalence with age. The 2 highest-risk subgroups identified by the signal detection analysis were composed of children with a parental history of asthma or hay fever who were 10 years or older with a body mass index greater than or equal to the 85th percentile (31.0% current asthma), and children with a parental history who were 10 years or younger and of African American ethnicity (15.6% current asthma). Conclusions: The findings from this analysis show a strong independent association between obesity and current asthma in children and adolescents, and confirm previous reports of a parental history of asthma or hay fever and African American ethnicity as additional important risk factors.	52	120	2002	7		Pediatrics
Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years. The primary aim of this study was to quantify and compare bronchodilator responsiveness in healthy and asthmatic children aged 2 to 5 yr. The secondary aim of the study was to compare discriminative capacity (i.e., sensitivity, specificity, and predictive values of the reversibility test for the diagnosis of asthma) for each of the lung function tests applied in the study. Specific airway resistance (sRaw) as measured by whole-body plethysmography, respiratory resistance as measured with the interrupter technique (Rint), and respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5, respectively) as measured with the impulse oscillation technique were assessed before and 20 min after inhalation of terbutaline from a pressurized metered-dose inhaler via a metal spacer by 92 children (37 healthy controls and 55 asthmatic subjects). The study of healthy children followed a randomized, double-blind, crossover design, whereas the study of asthmatic children was open. Baseline lung function was significantly decreased in asthmatic children as compared with healthy control subjects as reflected by all techniques used in the study. sRaw, Rint, and Rrs5, but not Xrs5, improved significantly with terbutaline as compared with placebo in healthy control subjects. Lung function Improved to a significantly greater extent in asthmatic children than in control subjects as reflected by all methods. sRaw provided the best discriminative power of such a bronchodilator response, with a sensitivity of 66% and specificity of 81% at the cutoff level of a 25% decrease in sRaw after bronchodilator administration. In conclusion, bronchodilator response measured by sRaw allows a separation of asthmatic from healthy young children. This may help define asthma in this clinically difficult-to-manage group of young wheezy children. The sensitivity and specificity of the other methods used in the study were less than those of sRaw.. healthy children| preschool children| bronchodilator responsiveness| lung function tests|airway-resistance| interrupter technique| oscillation technique| preschool-children| young-children| cold-air| plethysmography| reversibility| challenge.	AUG 15-2001	healthy children| preschool children| bronchodilator responsiveness| lung function tests|airway-resistance| interrupter technique| oscillation technique| preschool-children| young-children| cold-air| plethysmography| reversibility| challenge	Nielsen, KG; Bisgaard, H	Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	healthy children; preschool children; bronchodilator responsiveness; lung function tests	AIRWAY-RESISTANCE; INTERRUPTER TECHNIQUE; OSCILLATION TECHNIQUE; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; COLD-AIR; PLETHYSMOGRAPHY; REVERSIBILITY; CHALLENGE	The primary aim of this study was to quantify and compare bronchodilator responsiveness in healthy and asthmatic children aged 2 to 5 yr. The secondary aim of the study was to compare discriminative capacity (i.e., sensitivity, specificity, and predictive values of the reversibility test for the diagnosis of asthma) for each of the lung function tests applied in the study. Specific airway resistance (sRaw) as measured by whole-body plethysmography, respiratory resistance as measured with the interrupter technique (Rint), and respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5, respectively) as measured with the impulse oscillation technique were assessed before and 20 min after inhalation of terbutaline from a pressurized metered-dose inhaler via a metal spacer by 92 children (37 healthy controls and 55 asthmatic subjects). The study of healthy children followed a randomized, double-blind, crossover design, whereas the study of asthmatic children was open. Baseline lung function was significantly decreased in asthmatic children as compared with healthy control subjects as reflected by all techniques used in the study. sRaw, Rint, and Rrs5, but not Xrs5, improved significantly with terbutaline as compared with placebo in healthy control subjects. Lung function Improved to a significantly greater extent in asthmatic children than in control subjects as reflected by all methods. sRaw provided the best discriminative power of such a bronchodilator response, with a sensitivity of 66% and specificity of 81% at the cutoff level of a 25% decrease in sRaw after bronchodilator administration. In conclusion, bronchodilator response measured by sRaw allows a separation of asthmatic from healthy young children. This may help define asthma in this clinically difficult-to-manage group of young wheezy children. The sensitivity and specificity of the other methods used in the study were less than those of sRaw.	20	120	2001	6		General & Internal Medicine; Respiratory System
Long-lasting effects of sublingual immunotherapy according to its duration: A 15-year prospective study. Background: Data on the long-term effects of sublingual immunotherapy (SLIT) are sparse, and the optimal duration of treatment is a matter of debate. Objective: We sought to prospectively evaluate the long-term effect of SLIT given for 3, 4, or 5 years and to compare the effect of those different durations. Methods: In this prospective open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years. The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3, 4, or 5 years. Clinical scores, skin sensitizations, methacholine reactivity, and nasal eosinophil counts were evaluated every year during the winter months. The clinical effect was considered to persist until clinical scores remained at less than 50% of the baseline value, and then patients underwent another course of SLIT. Results: Seventy-eight patients were enrolled, and 59 completed the study. In the 12 control subjects no relevant change in clinical scores was seen throughout the study. In the patients receiving SLIT for 3 years, the clinical benefit persisted for 7 years. In those receiving immunotherapy for 4 or 5 years, the clinical benefit persisted for 8 years. New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT (21%, 12%, and 11%, respectively). The second course of vaccination induced a benefit more rapidly than the first course. The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score. Conclusion: Under the present conditions, it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination. (J Allergy Clin Immunol 2010;126:969-75.). sublingual immunotherapy| allergic rhinitis| long-lasting effect| house dust mite|grass-pollen immunotherapy| randomized controlled-trial| term clinical-efficacy| house-dust mite| respiratory allergy| immunoglobulin-e| position paper| follow-up| asthma| children.	NOV-2010	sublingual immunotherapy| allergic rhinitis| long-lasting effect| house dust mite|grass-pollen immunotherapy| randomized controlled-trial| term clinical-efficacy| house-dust mite| respiratory allergy| immunoglobulin-e| position paper| follow-up| asthma| children	Marogna, M; Spadolini, I; Massolo, A; Canonica, GW; Passalacqua, G	Long-lasting effects of sublingual immunotherapy according to its duration: A 15-year prospective study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Sublingual immunotherapy; allergic rhinitis; long-lasting effect; house dust mite	GRASS-POLLEN IMMUNOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; TERM CLINICAL-EFFICACY; HOUSE-DUST MITE; RESPIRATORY ALLERGY; IMMUNOGLOBULIN-E; POSITION PAPER; FOLLOW-UP; ASTHMA; CHILDREN	Background: Data on the long-term effects of sublingual immunotherapy (SLIT) are sparse, and the optimal duration of treatment is a matter of debate. Objective: We sought to prospectively evaluate the long-term effect of SLIT given for 3, 4, or 5 years and to compare the effect of those different durations. Methods: In this prospective open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years. The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3, 4, or 5 years. Clinical scores, skin sensitizations, methacholine reactivity, and nasal eosinophil counts were evaluated every year during the winter months. The clinical effect was considered to persist until clinical scores remained at less than 50% of the baseline value, and then patients underwent another course of SLIT. Results: Seventy-eight patients were enrolled, and 59 completed the study. In the 12 control subjects no relevant change in clinical scores was seen throughout the study. In the patients receiving SLIT for 3 years, the clinical benefit persisted for 7 years. In those receiving immunotherapy for 4 or 5 years, the clinical benefit persisted for 8 years. New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT (21%, 12%, and 11%, respectively). The second course of vaccination induced a benefit more rapidly than the first course. The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score. Conclusion: Under the present conditions, it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination. (J Allergy Clin Immunol 2010;126:969-75.)	28	119	2010	7	10.1016/j.jaci.2010.08.030	Allergy; Immunology
Dectin-2 Recognition of House Dust Mite Triggers Cysteinyl Leukotriene Generation by Dendritic Cells. House dust mites are a significant source of airborne allergen worldwide, but there is little understanding of how they so potently generate allergic inflammation. We found that extracts from the house dust mites Dermatophagoides farinae (Df) and Dermatophagoides pteronyssinus and from the mold Aspergillus fumigatus stimulated a rapid and robust production of cysteinyl leukotrienes (cys-LTs), proinflammatory lipid mediators, from mouse bone marrow-derived dendritic cells (BMDCs). Con A affinity chromatography of the Df extract revealed that the relevant ligand is a glycan(s), suggesting stimulation via a dendritic cell (DC) lectin receptor. Cys-LT production in BMDCs from wild-type mice was inhibited by spleen tyrosine kinase (Syk) inhibitors and was abolished in BMDCs from FcR gamma(-/-) mice, implicating either Dectin-2 or DC immunoactivating receptor. Transfection of each receptor in bone marrow-derived mast cells revealed that only Dectin-2 mediates cys-LT production by Df, Dermatophagoides pteronyssinus, and Aspergillus famigatus. Lentiviral knockdown of Dectin-2 in BMDCs attenuated Df extract-elicited cys-LT generation, thereby identifying Dectin-2 as the receptor. Lung CD11c(+) cells, but not peritoneal or alveolar macrophages, also generated cys-LTs in response to Df. These findings place Dectin-2 among the C-type lectin receptors that activate arachidonic acid metabolism and identify the Dectin-2/FcR gamma/Syk/cys-LT axis as a novel mechanism by which three potent indoor allergens may activate innate immune cells to promote allergic inflammation. The Journal of Immunology, 2009, 182: 1119-1128.. c-type lectin| mansoni egg antigens| allergic airway inflammation| arachidonic-acid cascade| receptor gamma-chain| mouse bone-marrow| human mast-cells| schistosoma-mansoni| dc-sign| pattern-recognition.	JAN 15-2009	c-type lectin| mansoni egg antigens| allergic airway inflammation| arachidonic-acid cascade| receptor gamma-chain| mouse bone-marrow| human mast-cells| schistosoma-mansoni| dc-sign| pattern-recognition	Barrett, NA; Maekawa, A; Rahman, OM; Austen, KF; Kanaoka, Y	Dectin-2 Recognition of House Dust Mite Triggers Cysteinyl Leukotriene Generation by Dendritic Cells		JOURNAL OF IMMUNOLOGY		C-TYPE LECTIN; MANSONI EGG ANTIGENS; ALLERGIC AIRWAY INFLAMMATION; ARACHIDONIC-ACID CASCADE; RECEPTOR GAMMA-CHAIN; MOUSE BONE-MARROW; HUMAN MAST-CELLS; SCHISTOSOMA-MANSONI; DC-SIGN; PATTERN-RECOGNITION	House dust mites are a significant source of airborne allergen worldwide, but there is little understanding of how they so potently generate allergic inflammation. We found that extracts from the house dust mites Dermatophagoides farinae (Df) and Dermatophagoides pteronyssinus and from the mold Aspergillus fumigatus stimulated a rapid and robust production of cysteinyl leukotrienes (cys-LTs), proinflammatory lipid mediators, from mouse bone marrow-derived dendritic cells (BMDCs). Con A affinity chromatography of the Df extract revealed that the relevant ligand is a glycan(s), suggesting stimulation via a dendritic cell (DC) lectin receptor. Cys-LT production in BMDCs from wild-type mice was inhibited by spleen tyrosine kinase (Syk) inhibitors and was abolished in BMDCs from FcR gamma(-/-) mice, implicating either Dectin-2 or DC immunoactivating receptor. Transfection of each receptor in bone marrow-derived mast cells revealed that only Dectin-2 mediates cys-LT production by Df, Dermatophagoides pteronyssinus, and Aspergillus famigatus. Lentiviral knockdown of Dectin-2 in BMDCs attenuated Df extract-elicited cys-LT generation, thereby identifying Dectin-2 as the receptor. Lung CD11c(+) cells, but not peritoneal or alveolar macrophages, also generated cys-LTs in response to Df. These findings place Dectin-2 among the C-type lectin receptors that activate arachidonic acid metabolism and identify the Dectin-2/FcR gamma/Syk/cys-LT axis as a novel mechanism by which three potent indoor allergens may activate innate immune cells to promote allergic inflammation. The Journal of Immunology, 2009, 182: 1119-1128.	64	119	2009	10		Immunology
Traffic-related atmospheric pollutants levels during pregnancy and offspring's term birth weight: a study relying on a land-use regression exposure model. BACKGROUND: Some studies have suggested that particulate matter (PM) levels during pregnancy may be associated with birth weight. Road traffic is a major source of fine PM (PM with aerodynamic diameter < 2.5 mu m; PM(2.5)). OBJECTIVE: We determined to characterize the influence of maternal exposure to atmospheric pollutants due to road traffic and urban activities on offspring term birth weight. METHODS: Women from a birth cohort [the LISA (Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children) cohort] who delivered a non-premature baby with a birth weight > 2,500 g in Munich metropolitan area were included. We assessed PM(2.5), PM(2.5) absorbance (which depends on the blackness of PM(2.5), a marker of traffic-related air pollution), and nitrogen dioxide levels using a land-use regression model, taking into account the type and length of roads, population density, land coverage around the home address, and temporal variations in pollution during pregnancy. Using Poisson regression, we estimated prevalence ratios (PR) of birth weight < 3,000 g, adjusted for gestational duration, sex, maternal smoking, height, weight, and education. RESULTS: Exposure was defined for 1,0 16 births. Taking the lowest quartile of exposure during pregnancy as a reference, the PR of birth weight < 3,000 g associated with the highest quartile was 1.7 for PM(2.5) [95% confidence interval (CI), 1.2-2.7], 1.8 for PM(2.5) absorbance (95% Cl, 1.1-2.7), and 1.2 for NO(2) (95% Cl, 0.7-1.7). The PR associated with an increase of 1 mu g/m(3) in PM(2.5) levels was 1. 13 (95% Cl, 1.00-1.29). CONCLUSION: Increases in PM(2.5) levels and PM(2.5) absorbance were associated with decreases in term birth weight. Traffic-related air pollutants may have adverse effects on birth weight.. atmospheric pollution| birth weight| diesel soot| environment| geographic information system| intrauterine growth restriction| particulate matter| pregnancy| reproduction| road traffic| sensitivity analysis|particulate air-pollution| polycyclic aromatic-hydrocarbons| los-angeles-county| fetal-growth| respiratory health| organic-compounds| maternal smoking| fine particles| dna-damage| outcomes.	SEP-2007	atmospheric pollution| birth weight| diesel soot| environment| geographic information system| intrauterine growth restriction| particulate matter| pregnancy| reproduction| road traffic| sensitivity analysis|particulate air-pollution| polycyclic aromatic-hydrocarbons| los-angeles-county| fetal-growth| respiratory health| organic-compounds| maternal smoking| fine particles| dna-damage| outcomes	Slama, R; Morgenstern, V; Cyrys, J; Zutavern, A; Herbarth, O; Wichmann, HE; Heinrich, J	Traffic-related atmospheric pollutants levels during pregnancy and offspring's term birth weight: a study relying on a land-use regression exposure model		ENVIRONMENTAL HEALTH PERSPECTIVES	atmospheric pollution; birth weight; diesel soot; environment; geographic information system; intrauterine growth restriction; particulate matter; pregnancy; reproduction; road traffic; sensitivity analysis	PARTICULATE AIR-POLLUTION; POLYCYCLIC AROMATIC-HYDROCARBONS; LOS-ANGELES-COUNTY; FETAL-GROWTH; RESPIRATORY HEALTH; ORGANIC-COMPOUNDS; MATERNAL SMOKING; FINE PARTICLES; DNA-DAMAGE; OUTCOMES	BACKGROUND: Some studies have suggested that particulate matter (PM) levels during pregnancy may be associated with birth weight. Road traffic is a major source of fine PM (PM with aerodynamic diameter < 2.5 mu m; PM(2.5)). OBJECTIVE: We determined to characterize the influence of maternal exposure to atmospheric pollutants due to road traffic and urban activities on offspring term birth weight. METHODS: Women from a birth cohort [the LISA (Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children) cohort] who delivered a non-premature baby with a birth weight > 2,500 g in Munich metropolitan area were included. We assessed PM(2.5), PM(2.5) absorbance (which depends on the blackness of PM(2.5), a marker of traffic-related air pollution), and nitrogen dioxide levels using a land-use regression model, taking into account the type and length of roads, population density, land coverage around the home address, and temporal variations in pollution during pregnancy. Using Poisson regression, we estimated prevalence ratios (PR) of birth weight < 3,000 g, adjusted for gestational duration, sex, maternal smoking, height, weight, and education. RESULTS: Exposure was defined for 1,0 16 births. Taking the lowest quartile of exposure during pregnancy as a reference, the PR of birth weight < 3,000 g associated with the highest quartile was 1.7 for PM(2.5) [95% confidence interval (CI), 1.2-2.7], 1.8 for PM(2.5) absorbance (95% Cl, 1.1-2.7), and 1.2 for NO(2) (95% Cl, 0.7-1.7). The PR associated with an increase of 1 mu g/m(3) in PM(2.5) levels was 1. 13 (95% Cl, 1.00-1.29). CONCLUSION: Increases in PM(2.5) levels and PM(2.5) absorbance were associated with decreases in term birth weight. Traffic-related air pollutants may have adverse effects on birth weight.	65	119	2007	10	10.1289/ehp.10047	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age. Background: Low intakes of dietary antioxidants may contribute to increases in asthma and allergy. Objective: We investigated the association of maternal total intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with wheezing and eczema in 2-y-old children. Design: Subjects were 1290 mother-child pairs in an ongoing cohort study. Maternal dietary and supplement intakes were assessed by using a validated food-frequency questionnaire administered in the first and second trimesters. Antioxidant nutrient intakes were calculated. and the mean for each nutrient was considered to be the exposure during pregnancy. The outcomes of interest were any wheezing by the child during either the first or second year of life, recurrent wheezing in both years, and eczema in either the first or second year. Results: No association was observed between maternal total intake of any antioxidant nutrient and eczema. In multivariate logistic regression models, the highest quartile compared with the lowest quartile of maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% Cl: 0.48,1.03] and zinc (OR: 0.59; 95% Cl: 0.41, 0.88) was inversely associated with any wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for vitamin E and zinc, respectively). Similar results were obtained for recurrent wheezing at 2 y of age with vitamin E (OR: 0.49; 95% Cl: 0.27, 0.90) and zinc (OR: 0.49; 95% Cl: 0.27. 0.87) (P for trend = 0.05 and 0.06 over quartiles of intake for vitamin E and zinc, respectively). Conclusion: Our results suggest that higher maternal total intakes of antioxidants during pregnancy may decrease the risks for wheezing illnesses in early childhood.. asthma| diet| antioxidants| eczema| childhood| wheezing|allergic rhinitis| childhood asthma| blood-pressure| hay-fever| national-health| dietary factors| united-states| lung-function| t-cells| risk.	OCT-2006	asthma| diet| antioxidants| eczema| childhood| wheezing|allergic rhinitis| childhood asthma| blood-pressure| hay-fever| national-health| dietary factors| united-states| lung-function| t-cells| risk	Litonjua, AA; Rifas-Shiman, SL; Ly, NP; Tantisira, KG; Rich-Edwards, JW; Camargo, CA; Weiss, ST; Gillman, MW; Gold, DR	Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age		AMERICAN JOURNAL OF CLINICAL NUTRITION	asthma; diet; antioxidants; eczema; childhood; wheezing	ALLERGIC RHINITIS; CHILDHOOD ASTHMA; BLOOD-PRESSURE; HAY-FEVER; NATIONAL-HEALTH; DIETARY FACTORS; UNITED-STATES; LUNG-FUNCTION; T-CELLS; RISK	Background: Low intakes of dietary antioxidants may contribute to increases in asthma and allergy. Objective: We investigated the association of maternal total intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with wheezing and eczema in 2-y-old children. Design: Subjects were 1290 mother-child pairs in an ongoing cohort study. Maternal dietary and supplement intakes were assessed by using a validated food-frequency questionnaire administered in the first and second trimesters. Antioxidant nutrient intakes were calculated. and the mean for each nutrient was considered to be the exposure during pregnancy. The outcomes of interest were any wheezing by the child during either the first or second year of life, recurrent wheezing in both years, and eczema in either the first or second year. Results: No association was observed between maternal total intake of any antioxidant nutrient and eczema. In multivariate logistic regression models, the highest quartile compared with the lowest quartile of maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% Cl: 0.48,1.03] and zinc (OR: 0.59; 95% Cl: 0.41, 0.88) was inversely associated with any wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for vitamin E and zinc, respectively). Similar results were obtained for recurrent wheezing at 2 y of age with vitamin E (OR: 0.49; 95% Cl: 0.27, 0.90) and zinc (OR: 0.49; 95% Cl: 0.27. 0.87) (P for trend = 0.05 and 0.06 over quartiles of intake for vitamin E and zinc, respectively). Conclusion: Our results suggest that higher maternal total intakes of antioxidants during pregnancy may decrease the risks for wheezing illnesses in early childhood.	61	119	2006	9		Nutrition & Dietetics
A future approach to measuring relative skin sensitising potency: a proposal. Current approaches to skin sensitisation risk assessment are dependent upon the availability of information regarding two fundamental parameters. Firstly, data relating to the relative skin sensitising potency of the chemical, and secondly, information regarding likely conditions of human exposure. During the past two decades, much has been achieved in terms of refining methods capable of informing these parameters. For example, the development of the local lymph node assay (LLNA) has made it possible to predict skin sensitising hazard, and to determine relative skin sensitising potency, in a way that was not possible previously. Taken together with accurate information about predicted exposure, such potency data can be used to facilitate the derivation of effective risk assessments. However, although the LLNA provides an integrated assessment of skin sensitising activity, it does require the use of experimental animals and there is growing enthusiasm for designing robust alternative approaches that will reduce or obviate that need. Progress is being made in defining alternative experimental strategies that avoid animal use, but it is clear that accurate characterisation of skin sensitisation hazards will require the effective integration of various sources of information. For this reason, we exemplify here one possible approach that, in theory, provides a framework for not only the identification of skin sensitising chemicals, but also the estimation of relative sensitising potency. This paradigm depends upon development of an understanding of the various biological, biochemical and chemical factors that impact on the allergenic properties of chemicals and the acquisition of skin sensitisation, and an ability to measure these in vitro. Copyright (c) 2006 John Wiley & Sons, Ltd.. skin| sensitisation| allergy| in vitro| in silico|lymph-node assay| epidermal langerhans cells| human dendritic cells| necrosis-factor-alpha| vitro primary sensitization| surface-marker expression| messenger-rna expression| in-vitro| contact sensitizers| iccvam evaluation.	JUL-AUG-2006	skin| sensitisation| allergy| in vitro| in silico|lymph-node assay| epidermal langerhans cells| human dendritic cells| necrosis-factor-alpha| vitro primary sensitization| surface-marker expression| messenger-rna expression| in-vitro| contact sensitizers| iccvam evaluation	Jowsey, IR; Basketter, DA; Westmoreland, C; Kimber, I	A future approach to measuring relative skin sensitising potency: a proposal		JOURNAL OF APPLIED TOXICOLOGY	skin; sensitisation; allergy; in vitro; in silico	LYMPH-NODE ASSAY; EPIDERMAL LANGERHANS CELLS; HUMAN DENDRITIC CELLS; NECROSIS-FACTOR-ALPHA; VITRO PRIMARY SENSITIZATION; SURFACE-MARKER EXPRESSION; MESSENGER-RNA EXPRESSION; IN-VITRO; CONTACT SENSITIZERS; ICCVAM EVALUATION	Current approaches to skin sensitisation risk assessment are dependent upon the availability of information regarding two fundamental parameters. Firstly, data relating to the relative skin sensitising potency of the chemical, and secondly, information regarding likely conditions of human exposure. During the past two decades, much has been achieved in terms of refining methods capable of informing these parameters. For example, the development of the local lymph node assay (LLNA) has made it possible to predict skin sensitising hazard, and to determine relative skin sensitising potency, in a way that was not possible previously. Taken together with accurate information about predicted exposure, such potency data can be used to facilitate the derivation of effective risk assessments. However, although the LLNA provides an integrated assessment of skin sensitising activity, it does require the use of experimental animals and there is growing enthusiasm for designing robust alternative approaches that will reduce or obviate that need. Progress is being made in defining alternative experimental strategies that avoid animal use, but it is clear that accurate characterisation of skin sensitisation hazards will require the effective integration of various sources of information. For this reason, we exemplify here one possible approach that, in theory, provides a framework for not only the identification of skin sensitising chemicals, but also the estimation of relative sensitising potency. This paradigm depends upon development of an understanding of the various biological, biochemical and chemical factors that impact on the allergenic properties of chemicals and the acquisition of skin sensitisation, and an ability to measure these in vitro. Copyright (c) 2006 John Wiley & Sons, Ltd.	53	119	2006	10	10.1002/jat.1146	Toxicology
Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation. Platelets are necessary for lung leukocyte recruitment in a murine model of allergic inflammation, and platelet-leukocyte aggregates are formed in circulating blood of patients with asthma after allergen exposure. However, it is unknown how platelets induce pulmonary leukocyte recruitment in asthma. Here, we have investigated the importance of platelet adhesion molecule expression on pulmonary eosinophil and lymphocyte recruitment and on leukocyte CD11b and very late antigen (VLA)-4 expression in mice. Pulmonary leukocyte recruitment in platelet-depleted mice (sensitized and exposed to ovalbumin) transfused with fixed, unstimulated platelets (FUSPs) was abolished, whereas transfusion with platelets stimulated and fixed (FSPs), expressing P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1), restored eosinophil and lymphocyte recruitment. Transfusion with platelets from P-selectin-deficient mice, or with FSPs stimulated in the presence of a blocking anti-P-selectin antibody, were unable to restore pulmonary leukocyte recruitment. Flow cytometric analysis revealed increased expression of CD11b and VLA-4 on leukocytes attached to platelets after allergen exposure, and CD11b expression on leukocytes was suppressed in thrombocytopenic mice but was restored with the transfusion of FSPs, but not FUSPs, a phenomenon concurrent with the formation of platelet-leukocyte complexes. P-selectin expression on the surfaces of platelets is a major requirement for pulmonary eosinophil and lymphocyte recruitment, allowing circulating platelets to bind to and stimulate leukocytes for endothelial attachment. (C) 2005 by The American Society of Hematology.. platelet/polymorphonuclear leukocyte interaction| endothelium in-vivo| glycoprotein ligand-1| bronchial-asthma| deficient mice| whole-blood| cross-talk| adhesion| beta(2)-integrin| cd11b/cd18.	MAR 1-2005	platelet/polymorphonuclear leukocyte interaction| endothelium in-vivo| glycoprotein ligand-1| bronchial-asthma| deficient mice| whole-blood| cross-talk| adhesion| beta(2)-integrin| cd11b/cd18	Pitchford, SC; Momi, S; Giannini, S; Casali, L; Spina, D; Page, CP; Gresele, P	Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation		BLOOD		PLATELET/POLYMORPHONUCLEAR LEUKOCYTE INTERACTION; ENDOTHELIUM IN-VIVO; GLYCOPROTEIN LIGAND-1; BRONCHIAL-ASTHMA; DEFICIENT MICE; WHOLE-BLOOD; CROSS-TALK; ADHESION; BETA(2)-INTEGRIN; CD11B/CD18	Platelets are necessary for lung leukocyte recruitment in a murine model of allergic inflammation, and platelet-leukocyte aggregates are formed in circulating blood of patients with asthma after allergen exposure. However, it is unknown how platelets induce pulmonary leukocyte recruitment in asthma. Here, we have investigated the importance of platelet adhesion molecule expression on pulmonary eosinophil and lymphocyte recruitment and on leukocyte CD11b and very late antigen (VLA)-4 expression in mice. Pulmonary leukocyte recruitment in platelet-depleted mice (sensitized and exposed to ovalbumin) transfused with fixed, unstimulated platelets (FUSPs) was abolished, whereas transfusion with platelets stimulated and fixed (FSPs), expressing P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1), restored eosinophil and lymphocyte recruitment. Transfusion with platelets from P-selectin-deficient mice, or with FSPs stimulated in the presence of a blocking anti-P-selectin antibody, were unable to restore pulmonary leukocyte recruitment. Flow cytometric analysis revealed increased expression of CD11b and VLA-4 on leukocytes attached to platelets after allergen exposure, and CD11b expression on leukocytes was suppressed in thrombocytopenic mice but was restored with the transfusion of FSPs, but not FUSPs, a phenomenon concurrent with the formation of platelet-leukocyte complexes. P-selectin expression on the surfaces of platelets is a major requirement for pulmonary eosinophil and lymphocyte recruitment, allowing circulating platelets to bind to and stimulate leukocytes for endothelial attachment. (C) 2005 by The American Society of Hematology.	41	119	2005	8	10.1182/blood-2004-06-2282	Hematology
"Role of antibiotics and fungal microbiota in driving pulmonary allergic responses. Over the past four decades, there has been a significant increase in allergy and asthma in westernized countries, which correlates with alterations in fecal microbiota (microflora) and widespread use of antibiotics (the ""hygiene hypothesis""). Antibiotics also lead to overgrowth of the yeast Candida albicans, which can secrete potent prostaglandin-like immune response modulators. We have developed a mouse model of antibiotic-induced microbiota disruption that includes stable increases in gastrointestinal (GI) enteric bacteria and GI Candida levels with no introduction of microbes into the lungs. Mice are treated for 5 days with cefoperazone in the drinking water, followed by a single oral gavage of C albicans. This results in alterations of GI bacterial populations and increased yeast numbers in the GI microbiota for at least 2 to 3 weeks and can drive the development of a CD4 T-cell-mediated allergic airway response to subsequent mold spore (Aspergillus fumigatus) exposure in immunocompetent mice without previous systemic antigen priming. The allergic response in the lungs is characterized by increased levels of eosinophils, mast cells, interleukin-5 (IL-5), IL-13, gamma interferon, immunoglobulin E, and mucus-secreting cells. In the absence of antibiotics, mice exposed to Aspergillus spores do not develop an allergic response in the airways. This study provides the first experimental evidence to support a role for antibiotics and fungal microbiota in promoting the development of allergic airway disease. In addition, these studies also highlight the concept that events in distal mucosal sites such as the GI tract can play an important role in regulating immune responses in the lungs.. oral tolerance induction| regulatory t-cells| bronchopulmonary aspergillosis| candida-albicans| murine model| airway hyperreactivity| lymphokine production| prostaglandin d-2| early-childhood| peyers-patches."	SEP-2004	oral tolerance induction| regulatory t-cells| bronchopulmonary aspergillosis| candida-albicans| murine model| airway hyperreactivity| lymphokine production| prostaglandin d-2| early-childhood| peyers-patches	Noverr, MC; Noggle, RM; Toews, GB; Huffnagle, GB	Role of antibiotics and fungal microbiota in driving pulmonary allergic responses		INFECTION AND IMMUNITY		ORAL TOLERANCE INDUCTION; REGULATORY T-CELLS; BRONCHOPULMONARY ASPERGILLOSIS; CANDIDA-ALBICANS; MURINE MODEL; AIRWAY HYPERREACTIVITY; LYMPHOKINE PRODUCTION; PROSTAGLANDIN D-2; EARLY-CHILDHOOD; PEYERS-PATCHES	"Over the past four decades, there has been a significant increase in allergy and asthma in westernized countries, which correlates with alterations in fecal microbiota (microflora) and widespread use of antibiotics (the ""hygiene hypothesis""). Antibiotics also lead to overgrowth of the yeast Candida albicans, which can secrete potent prostaglandin-like immune response modulators. We have developed a mouse model of antibiotic-induced microbiota disruption that includes stable increases in gastrointestinal (GI) enteric bacteria and GI Candida levels with no introduction of microbes into the lungs. Mice are treated for 5 days with cefoperazone in the drinking water, followed by a single oral gavage of C albicans. This results in alterations of GI bacterial populations and increased yeast numbers in the GI microbiota for at least 2 to 3 weeks and can drive the development of a CD4 T-cell-mediated allergic airway response to subsequent mold spore (Aspergillus fumigatus) exposure in immunocompetent mice without previous systemic antigen priming. The allergic response in the lungs is characterized by increased levels of eosinophils, mast cells, interleukin-5 (IL-5), IL-13, gamma interferon, immunoglobulin E, and mucus-secreting cells. In the absence of antibiotics, mice exposed to Aspergillus spores do not develop an allergic response in the airways. This study provides the first experimental evidence to support a role for antibiotics and fungal microbiota in promoting the development of allergic airway disease. In addition, these studies also highlight the concept that events in distal mucosal sites such as the GI tract can play an important role in regulating immune responses in the lungs."	71	119	2004	8	10.1128/IAI.72.9.4996-5003.2004	Immunology; Infectious Diseases
Characterization of drug-specific T cells in lamotrigine hypersensitivity. Background: Lamotrigine is associated with hypersensitivity reactions, which are most commonly characterized by skin rash. An immune etiology has been postulated, though the nature of this is unclear. Objectives: The aim of this study was to characterize the role of T cells in lamotrigine hypersensitivity. Methods: A lymphocyte transformation test was performed on 4 hypersensitive patients. Lymphocytes from 3 of 4 lamotrigine-hypersensitive patients proliferated when stimulated with lamotrigine. T-cell clones were generated from one patient to further characterize the nature of the T-cell involvement. Cells were characterized in terms of their phenotype, functionality, and mechanisms of antigen presentation and cytotoxicity. Results: Of the 44 drug-specific T-cell clones generated, most were CD4(+) with occasional CD8(+) cells. All clones expressed the up T-cell receptor; several Vbeta 5.1(+) or 9(+) T-cell clones were generated. All clones also expressed the skin-homing receptor cutaneous lymphocyte antigen. Lamotrigine-stimulated T cells were cytotoxic and secreted perforin, IFN-gamma, IL-5, and macrophage inflammatory protein la, macrophage inflammatory protein 1beta, RANTES, and I-309. Lamotrigine was present on HLA-DR and HLA-DQ by antigen-presenting cells in the absence of drug metabolism and processing. The T-cell receptor of certain clones could accommodate analogs of lamotrigine, but no cross-reactivity was seen with other anticonvulsants. Conclusions: Our data provide evidence that T cells are involved in the pathogenesis of some lamotrigine-hypersensitivity reactions. The identification of drug-specific cells that express cutaneous lymphocyte antigen and type 1 cytokines after T-cell receptor activation is consistent with the clinical symptoms. Furthermore, identification of large numbers of Vbeta 5.1(+) T cells suggests that polymorphisms within T-cell receptor genes might act as determinants of susceptibility. (J Allergy Clin Immunol 2003;111:1393-1403.).. lamotrigine| anticonvulsant hypersensitivity| t cells| antigen processing| cytokines| chemokines| t-cell receptors|toxic epidermal necrolysis| lymphocyte-transformation test| reactive metabolites| covalent binding| in-vitro| carbamazepine| recognition| sulfamethoxazole| clones| skin.	JUN-2003	lamotrigine| anticonvulsant hypersensitivity| t cells| antigen processing| cytokines| chemokines| t-cell receptors|toxic epidermal necrolysis| lymphocyte-transformation test| reactive metabolites| covalent binding| in-vitro| carbamazepine| recognition| sulfamethoxazole| clones| skin	Naisbitt, DJ; Farrell, J; Wong, G; Depta, JPH; Dodd, CC; Hopkins, JE; Gibney, CA; Chadwick, DW; Pickler, WJ; Pirmohamed, M; Park, BK	Characterization of drug-specific T cells in lamotrigine hypersensitivity		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	lamotrigine; anticonvulsant hypersensitivity; T cells; antigen processing; cytokines; chemokines; T-cell receptors	TOXIC EPIDERMAL NECROLYSIS; LYMPHOCYTE-TRANSFORMATION TEST; REACTIVE METABOLITES; COVALENT BINDING; IN-VITRO; CARBAMAZEPINE; RECOGNITION; SULFAMETHOXAZOLE; CLONES; SKIN	Background: Lamotrigine is associated with hypersensitivity reactions, which are most commonly characterized by skin rash. An immune etiology has been postulated, though the nature of this is unclear. Objectives: The aim of this study was to characterize the role of T cells in lamotrigine hypersensitivity. Methods: A lymphocyte transformation test was performed on 4 hypersensitive patients. Lymphocytes from 3 of 4 lamotrigine-hypersensitive patients proliferated when stimulated with lamotrigine. T-cell clones were generated from one patient to further characterize the nature of the T-cell involvement. Cells were characterized in terms of their phenotype, functionality, and mechanisms of antigen presentation and cytotoxicity. Results: Of the 44 drug-specific T-cell clones generated, most were CD4(+) with occasional CD8(+) cells. All clones expressed the up T-cell receptor; several Vbeta 5.1(+) or 9(+) T-cell clones were generated. All clones also expressed the skin-homing receptor cutaneous lymphocyte antigen. Lamotrigine-stimulated T cells were cytotoxic and secreted perforin, IFN-gamma, IL-5, and macrophage inflammatory protein la, macrophage inflammatory protein 1beta, RANTES, and I-309. Lamotrigine was present on HLA-DR and HLA-DQ by antigen-presenting cells in the absence of drug metabolism and processing. The T-cell receptor of certain clones could accommodate analogs of lamotrigine, but no cross-reactivity was seen with other anticonvulsants. Conclusions: Our data provide evidence that T cells are involved in the pathogenesis of some lamotrigine-hypersensitivity reactions. The identification of drug-specific cells that express cutaneous lymphocyte antigen and type 1 cytokines after T-cell receptor activation is consistent with the clinical symptoms. Furthermore, identification of large numbers of Vbeta 5.1(+) T cells suggests that polymorphisms within T-cell receptor genes might act as determinants of susceptibility. (J Allergy Clin Immunol 2003;111:1393-1403.).	44	119	2003	11	10.1067/mai.2003.1507	Allergy; Immunology
Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up. Background: Childhood asthma is generally believed to be a disorder with a good prognosis. However, some asthmatics develop irreversible airway obstruction, probably as a result of airway remodelling. Methods: After 21-33 years, 228 adults (aged 13-44 years at baseline) with a history of asthma were re-examined to assess risk factors for the development of irreversible airway obstruction (IAO, forced expiratory volume in 1 second (FEV1) <80% predicted and reversibility <9% predicted) and a reduced postbronchodilator transfer coefficient (carbon monoxide transfer factor/alveolar volume, <80% predicted), both characteristics of COPD. Results: At follow up, 41% did not have airway obstruction (NAO), 43% had reversible airway obstruction (RAO), and 16% had IAO; 23% had a reduced transfer coefficient. Patients with RAO had asthma-like characteristics (wheezing, asthma attacks, bronchial hyperresponsiveness (BHR)) while patients with IAO had COPD-like symptoms (cough, phlegm, dyspnoea) at follow up. The development of IAO is determined by a lower FEV1, less reversibility of airway obstruction and, surprisingly, less severe BHR at initial screening. Eighty percent of the patients with asthma who used anti-inflammatory medication still had airway obstruction, but IAO developed less frequently. Smoking was associated with a reduced transfer coefficient but not with the development of IAO. Female sex was associated with a reduced transfer coefficient, whereas corticosteroid use was not. Conclusions: Although IAO and a low transfer coefficient are both characteristics of COPD, they represent distinct entities in adult asthmatics in terms of symptomatology, aetiology, and probably in therapeutic approaches and disease prevention.. air-flow obstruction| lung-function| respiratory symptoms| pulmonary-function| bronchial-asthma| decline| childhood| adults| hyperresponsiveness| persistence.	APR-2003	air-flow obstruction| lung-function| respiratory symptoms| pulmonary-function| bronchial-asthma| decline| childhood| adults| hyperresponsiveness| persistence	Vonk, JM; Jongepier, H; Panhuysen, CIM; Schouten, JP; Bleecker, ER; Postma, DS	Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up		THORAX		AIR-FLOW OBSTRUCTION; LUNG-FUNCTION; RESPIRATORY SYMPTOMS; PULMONARY-FUNCTION; BRONCHIAL-ASTHMA; DECLINE; CHILDHOOD; ADULTS; HYPERRESPONSIVENESS; PERSISTENCE	Background: Childhood asthma is generally believed to be a disorder with a good prognosis. However, some asthmatics develop irreversible airway obstruction, probably as a result of airway remodelling. Methods: After 21-33 years, 228 adults (aged 13-44 years at baseline) with a history of asthma were re-examined to assess risk factors for the development of irreversible airway obstruction (IAO, forced expiratory volume in 1 second (FEV1) <80% predicted and reversibility <9% predicted) and a reduced postbronchodilator transfer coefficient (carbon monoxide transfer factor/alveolar volume, <80% predicted), both characteristics of COPD. Results: At follow up, 41% did not have airway obstruction (NAO), 43% had reversible airway obstruction (RAO), and 16% had IAO; 23% had a reduced transfer coefficient. Patients with RAO had asthma-like characteristics (wheezing, asthma attacks, bronchial hyperresponsiveness (BHR)) while patients with IAO had COPD-like symptoms (cough, phlegm, dyspnoea) at follow up. The development of IAO is determined by a lower FEV1, less reversibility of airway obstruction and, surprisingly, less severe BHR at initial screening. Eighty percent of the patients with asthma who used anti-inflammatory medication still had airway obstruction, but IAO developed less frequently. Smoking was associated with a reduced transfer coefficient but not with the development of IAO. Female sex was associated with a reduced transfer coefficient, whereas corticosteroid use was not. Conclusions: Although IAO and a low transfer coefficient are both characteristics of COPD, they represent distinct entities in adult asthmatics in terms of symptomatology, aetiology, and probably in therapeutic approaches and disease prevention.	26	119	2003	6	10.1136/thorax.58.4.322	Respiratory System
The role of immunoglobulin E in allergy and asthma. it has been nearly a century since the first suggestion that a soluble factor in plasma or serum might be responsible for the symptoms of allergic disease and asthma, and more than 30 yr since immunoglobulin E (IgE) was identified as the key molecule in mediating what are now described as type 1 hypersensitivity reactions (allergic asthma, allergic rhinitis, food allergy, atopic dermatitis, some forms of drug allergy, and insect sting allergy). Since that time, many of the details of the inflammatory cascade underlying allergy and asthma have been elucidated, and IgE is now known to play a key upstream role. The goals of this report are to review the cellular and molecular events set in motion by IgE and to examine the evidence for its participation in both the immediate allergic response and the late-phase or chronic inflammatory response in the skin and lungs.. pathophysiology| asthma| allergy| ige| allergic cascade|house-dust mite| skin-test reactivity| fc-epsilon-ri| mast-cells| serum ige| airway responsiveness| atopic-dermatitis| childhood asthma| early exposure| children.	OCT 15-2001	pathophysiology| asthma| allergy| ige| allergic cascade|house-dust mite| skin-test reactivity| fc-epsilon-ri| mast-cells| serum ige| airway responsiveness| atopic-dermatitis| childhood asthma| early exposure| children	Platts-Mills, TAE	The role of immunoglobulin E in allergy and asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	pathophysiology; asthma; allergy; IgE; allergic cascade	HOUSE-DUST MITE; SKIN-TEST REACTIVITY; FC-EPSILON-RI; MAST-CELLS; SERUM IGE; AIRWAY RESPONSIVENESS; ATOPIC-DERMATITIS; CHILDHOOD ASTHMA; EARLY EXPOSURE; CHILDREN	it has been nearly a century since the first suggestion that a soluble factor in plasma or serum might be responsible for the symptoms of allergic disease and asthma, and more than 30 yr since immunoglobulin E (IgE) was identified as the key molecule in mediating what are now described as type 1 hypersensitivity reactions (allergic asthma, allergic rhinitis, food allergy, atopic dermatitis, some forms of drug allergy, and insect sting allergy). Since that time, many of the details of the inflammatory cascade underlying allergy and asthma have been elucidated, and IgE is now known to play a key upstream role. The goals of this report are to review the cellular and molecular events set in motion by IgE and to examine the evidence for its participation in both the immediate allergic response and the late-phase or chronic inflammatory response in the skin and lungs.	35	119	2001	5		General & Internal Medicine; Respiratory System
Fragrance chemicals in domestic and occupational products. Epidemiological studies have described an increasing prevalence of fragrance allergy and indicated an association with hand eczema. 59 domestic and occupational products intended for hand exposure were subjected to gas chromatography-mass spectrometric (GC-MS) analyses to test the hypothesis that fragrance chemicals known to have the potential to cause contact allergy but not included in fragrance mix (FM) may be common ingredients in these products. A quantitative analysis of 19 selected fragrances was performed by GC-MS. Further analysis of GC-MS data revealed the presence of 43 other fragrance chemicals/groups of fragrance chemicals in the products investigated. Among the 19 target substances the most commonly detected were limonene in 78%, linalool in 61% and citronellol in 47% of the products investigated. The FM ingredients were present in these products with the following frequencies: oak moss (evernic acid methylester) 2%, cinnamic, alcohol 2%, cinnamic aldehyde (cinnamal) 3%, isoeugenol 5%, alpha -amylcinnamic aldehyde (amyl cinnamal) 8%, hydroxycitronellal 12%, eugenol 27%, and geraniol 41%. Thus, the chemical analyses of domestic and occupational products indicates that investigation of potential contact allergy related to these products types should consider fragrance allergens additional to those in the FM, since these may occur with high frequency. (C) Munksgaard, 2001.. fragrance chemicals| domestic and occupational products| chemical analysis| fragrance mix (fm)|contact allergy| patch test| constituents| mix| dermatitis| deodorants| cosmetics| perfumes.	OCT-2001	fragrance chemicals| domestic and occupational products| chemical analysis| fragrance mix (fm)|contact allergy| patch test| constituents| mix| dermatitis| deodorants| cosmetics| perfumes	Rastogi, SC; Heydorn, S; Johansen, JD; Basketter, DA	Fragrance chemicals in domestic and occupational products		CONTACT DERMATITIS	fragrance chemicals; domestic and occupational products; chemical analysis; fragrance mix (FM)	CONTACT ALLERGY; PATCH TEST; CONSTITUENTS; MIX; DERMATITIS; DEODORANTS; COSMETICS; PERFUMES	Epidemiological studies have described an increasing prevalence of fragrance allergy and indicated an association with hand eczema. 59 domestic and occupational products intended for hand exposure were subjected to gas chromatography-mass spectrometric (GC-MS) analyses to test the hypothesis that fragrance chemicals known to have the potential to cause contact allergy but not included in fragrance mix (FM) may be common ingredients in these products. A quantitative analysis of 19 selected fragrances was performed by GC-MS. Further analysis of GC-MS data revealed the presence of 43 other fragrance chemicals/groups of fragrance chemicals in the products investigated. Among the 19 target substances the most commonly detected were limonene in 78%, linalool in 61% and citronellol in 47% of the products investigated. The FM ingredients were present in these products with the following frequencies: oak moss (evernic acid methylester) 2%, cinnamic, alcohol 2%, cinnamic aldehyde (cinnamal) 3%, isoeugenol 5%, alpha -amylcinnamic aldehyde (amyl cinnamal) 8%, hydroxycitronellal 12%, eugenol 27%, and geraniol 41%. Thus, the chemical analyses of domestic and occupational products indicates that investigation of potential contact allergy related to these products types should consider fragrance allergens additional to those in the FM, since these may occur with high frequency. (C) Munksgaard, 2001.	15	119	2001	5	10.1034/j.1600-0536.2001.450406.x	Allergy; Dermatology
Th2 polarization by Der p 1-pulsed monocyte-derived dendritic cells is due to the allergic status of the donors. The polarization of the immune response toward a Th2 or a Th1 profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such as CD80 and CD86 expressed by DCs, the polarizing cytokine environment during DC-T-cell interaction, and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides, pteronyssinus, on these different parameters was evaluated comparatively on monocyte-derived DCs obtained from healthy donors, from pollen-sensitive patients, or from patients sensitive to Dermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite-sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the production of proinflammatory cytokines, tumor necrosis factor-alpha and interleukin (IL)-1 beta, and the type 2 cytokine IL-10. No changes in the release of IL-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite-sensitive patients stimulated by autologous Der p 1-pulsed DCs preferentially produced IL-4 rather than interferon-gamma. These effects were abolished ih the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs from house dust mite-sensitive patients, in contrast to DCs from healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated with the allergic reaction developed in response to house dust mite exposure.. dust mite allergen| costimulatory molecules| interleukin (il)-12| atopic-dermatitis| langerhans cells| down-regulation| up-regulation| ige synthesis| class-ii| t-cells.	AUG 15-2001	dust mite allergen| costimulatory molecules| interleukin (il)-12| atopic-dermatitis| langerhans cells| down-regulation| up-regulation| ige synthesis| class-ii| t-cells	Hammad, H; Charbonnier, AS; Duez, C; Jacquet, A; Stewart, GA; Tonnel, AB; Pestel, J	Th2 polarization by Der p 1-pulsed monocyte-derived dendritic cells is due to the allergic status of the donors		BLOOD		DUST MITE ALLERGEN; COSTIMULATORY MOLECULES; INTERLEUKIN (IL)-12; ATOPIC-DERMATITIS; LANGERHANS CELLS; DOWN-REGULATION; UP-REGULATION; IGE SYNTHESIS; CLASS-II; T-CELLS	The polarization of the immune response toward a Th2 or a Th1 profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such as CD80 and CD86 expressed by DCs, the polarizing cytokine environment during DC-T-cell interaction, and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides, pteronyssinus, on these different parameters was evaluated comparatively on monocyte-derived DCs obtained from healthy donors, from pollen-sensitive patients, or from patients sensitive to Dermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite-sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the production of proinflammatory cytokines, tumor necrosis factor-alpha and interleukin (IL)-1 beta, and the type 2 cytokine IL-10. No changes in the release of IL-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite-sensitive patients stimulated by autologous Der p 1-pulsed DCs preferentially produced IL-4 rather than interferon-gamma. These effects were abolished ih the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs from house dust mite-sensitive patients, in contrast to DCs from healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated with the allergic reaction developed in response to house dust mite exposure.	36	119	2001	7	10.1182/blood.V98.4.1135	Hematology
Control of T Helper 2 Responses by Transcription Factor IRF4-Dependent Dendritic Cells. CD4(+) T cell differentiation is regulated by specialized antigen-presenting cells. Dendritic cells (DCs) produce cytokines that promote naive CD4(+) T cell differentiation into T helper 1 (Th1), Th17, and inducible T regulatory (iTreg) cells. However, the initiation of Th2 cell responses remains poorly understood, although it is likely that more than one mechanism might be involved. Here we have defined a specific DC subset that is involved in Th2 cell differentiation in vivo in response to a protease allergen, as well as infection with Nippostrongylus brasiliensis. We have demonstrated that this subset is controlled by the transcription factor interferon regulatory factor 4 (IRF4), which is required for their differentiation and Th2 cell-inducing function. IRF4 is known to control Th2 cell differentiation and Th2 cell-associated suppressing function in Treg cells. Our finding suggests that IRF4 also plays a role in DCs where it controls the initiation of Th2 cell responses.. interferon regulatory factor-4| dust mite allergen| in-vivo| type-2 immunity| contact hypersensitivity| lymph-nodes| t-cells| differentiation| expression| specification.	OCT 17-2013	interferon regulatory factor-4| dust mite allergen| in-vivo| type-2 immunity| contact hypersensitivity| lymph-nodes| t-cells| differentiation| expression| specification	Gao, Y; Nish, SA; Jiang, RY; Hou, L; Licona-Limon, P; Weinstein, JS; Zhao, HY; Medzhitov, R	Control of T Helper 2 Responses by Transcription Factor IRF4-Dependent Dendritic Cells		IMMUNITY		INTERFERON REGULATORY FACTOR-4; DUST MITE ALLERGEN; IN-VIVO; TYPE-2 IMMUNITY; CONTACT HYPERSENSITIVITY; LYMPH-NODES; T-CELLS; DIFFERENTIATION; EXPRESSION; SPECIFICATION	CD4(+) T cell differentiation is regulated by specialized antigen-presenting cells. Dendritic cells (DCs) produce cytokines that promote naive CD4(+) T cell differentiation into T helper 1 (Th1), Th17, and inducible T regulatory (iTreg) cells. However, the initiation of Th2 cell responses remains poorly understood, although it is likely that more than one mechanism might be involved. Here we have defined a specific DC subset that is involved in Th2 cell differentiation in vivo in response to a protease allergen, as well as infection with Nippostrongylus brasiliensis. We have demonstrated that this subset is controlled by the transcription factor interferon regulatory factor 4 (IRF4), which is required for their differentiation and Th2 cell-inducing function. IRF4 is known to control Th2 cell differentiation and Th2 cell-associated suppressing function in Treg cells. Our finding suggests that IRF4 also plays a role in DCs where it controls the initiation of Th2 cell responses.	43	118	2013	11	10.1016/j.immuni.2013.08.028	Immunology
Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy. Background: Both gastrointestinal microbiota composition and cesarean section have been linked to atopic manifestations. However, results are inconsistent, and the hypothesized intermediate role of the microbiota in the association between birth mode and atopic manifestations has not been studied yet. Objectives: We sought to investigate the relationship between microbiota composition, mode and place of delivery, and atopic manifestations. Methods: The Child, Parent and Health: Lifestyle and Genetic Constitution Birth Cohort Study included data on birth characteristics, lifestyle factors, and atopic manifestations collected through repeated questionnaires from birth until age 7 years. Fecal samples were collected at age 1 month (n = 1176) to determine microbiota composition, and blood samples were collected at ages 1 (n = 921), 2 (n = 822), and 6 to 7 (n = 384) years to determine specific IgE levels. Results: Colonization by Clostridium difficile at age 1 month was associated with wheeze and eczema throughout the first 6 to 7 years of life and with asthma at age 6 to 7 years. Vaginal home delivery compared with vaginal hospital delivery was associated with a decreased risk of eczema, sensitization to food allergens, and asthma. After stratification for parental history of atopy, the decreased risk of sensitization to food allergens (adjusted odds ratio, 0.52; 95% CI, 0.35-0.77) and asthma (adjusted odds ratio, 0.47; 95% CI, 0.29-0.77) among vaginally home-born infants was only found for children with atopic parents. Mediation analysis showed that the effects of mode and place of delivery on atopic outcomes were mediated by C difficile colonization. Conclusion: Mode and place of delivery affect the gastrointestinal microbiota composition, which subsequently influences the risk of atopic manifestations. (J Allergy Clin Immunol 2011;128:948-55.). mode of delivery| cesarean section| hospital delivery| gastrointestinal microbiota composition| wheeze| eczema| asthma| atopy| mediation analysis| cohort study| koala study|koala birth cohort| intestinal microflora| cesarean-section| fecal microflora| childhood| allergy| children| infants| risk| gut.	NOV-2011	mode of delivery| cesarean section| hospital delivery| gastrointestinal microbiota composition| wheeze| eczema| asthma| atopy| mediation analysis| cohort study| koala study|koala birth cohort| intestinal microflora| cesarean-section| fecal microflora| childhood| allergy| children| infants| risk| gut	van Nimwegen, FA; Penders, J; Stobberingh, EE; Postma, DS; Koppelman, GH; Kerkhof, M; Reijmerink, NE; Dompeling, E; van den Brandt, PA; Ferreira, I; Mommers, M; Thijs, C	Mode and place of delivery, gastrointestinal microbiota, and their influence on asthma and atopy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Mode of delivery; cesarean section; hospital delivery; gastrointestinal microbiota composition; wheeze; eczema; asthma; atopy; mediation analysis; cohort study; KOALA study	KOALA BIRTH COHORT; INTESTINAL MICROFLORA; CESAREAN-SECTION; FECAL MICROFLORA; CHILDHOOD; ALLERGY; CHILDREN; INFANTS; RISK; GUT	Background: Both gastrointestinal microbiota composition and cesarean section have been linked to atopic manifestations. However, results are inconsistent, and the hypothesized intermediate role of the microbiota in the association between birth mode and atopic manifestations has not been studied yet. Objectives: We sought to investigate the relationship between microbiota composition, mode and place of delivery, and atopic manifestations. Methods: The Child, Parent and Health: Lifestyle and Genetic Constitution Birth Cohort Study included data on birth characteristics, lifestyle factors, and atopic manifestations collected through repeated questionnaires from birth until age 7 years. Fecal samples were collected at age 1 month (n = 1176) to determine microbiota composition, and blood samples were collected at ages 1 (n = 921), 2 (n = 822), and 6 to 7 (n = 384) years to determine specific IgE levels. Results: Colonization by Clostridium difficile at age 1 month was associated with wheeze and eczema throughout the first 6 to 7 years of life and with asthma at age 6 to 7 years. Vaginal home delivery compared with vaginal hospital delivery was associated with a decreased risk of eczema, sensitization to food allergens, and asthma. After stratification for parental history of atopy, the decreased risk of sensitization to food allergens (adjusted odds ratio, 0.52; 95% CI, 0.35-0.77) and asthma (adjusted odds ratio, 0.47; 95% CI, 0.29-0.77) among vaginally home-born infants was only found for children with atopic parents. Mediation analysis showed that the effects of mode and place of delivery on atopic outcomes were mediated by C difficile colonization. Conclusion: Mode and place of delivery affect the gastrointestinal microbiota composition, which subsequently influences the risk of atopic manifestations. (J Allergy Clin Immunol 2011;128:948-55.)	32	118	2011	11	10.1016/j.jaci.2011.07.027	Allergy; Immunology
Recent warming by latitude associated with increased length of ragweed pollen season in central North America. A fundamental aspect of climate change is the potential shifts in flowering phenology and pollen initiation associated with milder winters and warmer seasonal air temperature. Earlier floral anthesis has been suggested, in turn, to have a role in human disease by increasing time of exposure to pollen that causes allergic rhinitis and related asthma. However, earlier floral initiation does not necessarily alter the temporal duration of the pollen season, and, to date, no consistent continental trend in pollen season length has been demonstrated. Here we report that duration of the ragweed (Ambrosia spp.) pollen season has been increasing in recent decades as a function of latitude in North America. Latitudinal effects on increasing season length were associated primarily with a delay in first frost of the fall season and lengthening of the frost free period. Overall, these data indicate a significant increase in the length of the ragweed pollen season by as much as 13-27 d at latitudes above similar to 44 degrees N since 1995. This is consistent with recent Intergovernmental Panel on Climate Change projections regarding enhanced warming as a function of latitude. If similar warming trends accompany long-term climate change, greater exposure times to seasonal allergens may occur with subsequent effects on public health.. aerobiology| allergies| global warming|ambrosia-artemisiifolia l.| climate-change| common ragweed| public-health| united-states| aeroallergens| allergy| urbanization| temperatures| counts.	MAR 8-2011	aerobiology| allergies| global warming|ambrosia-artemisiifolia l.| climate-change| common ragweed| public-health| united-states| aeroallergens| allergy| urbanization| temperatures| counts	Ziska, L; Knowlton, K; Rogers, C; Dalan, D; Tierney, N; Elder, MA; Filley, W; Shropshire, J; Ford, LB; Hedberg, C; Fleetwood, P; Hovanky, KT; Kavanaugh, T; Fulford, G; Vrtis, RF; Patz, JA; Portnoy, J; Coates, F; Bielory, L; Frenz, D	Recent warming by latitude associated with increased length of ragweed pollen season in central North America		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	aerobiology; allergies; global warming	AMBROSIA-ARTEMISIIFOLIA L.; CLIMATE-CHANGE; COMMON RAGWEED; PUBLIC-HEALTH; UNITED-STATES; AEROALLERGENS; ALLERGY; URBANIZATION; TEMPERATURES; COUNTS	A fundamental aspect of climate change is the potential shifts in flowering phenology and pollen initiation associated with milder winters and warmer seasonal air temperature. Earlier floral anthesis has been suggested, in turn, to have a role in human disease by increasing time of exposure to pollen that causes allergic rhinitis and related asthma. However, earlier floral initiation does not necessarily alter the temporal duration of the pollen season, and, to date, no consistent continental trend in pollen season length has been demonstrated. Here we report that duration of the ragweed (Ambrosia spp.) pollen season has been increasing in recent decades as a function of latitude in North America. Latitudinal effects on increasing season length were associated primarily with a delay in first frost of the fall season and lengthening of the frost free period. Overall, these data indicate a significant increase in the length of the ragweed pollen season by as much as 13-27 d at latitudes above similar to 44 degrees N since 1995. This is consistent with recent Intergovernmental Panel on Climate Change projections regarding enhanced warming as a function of latitude. If similar warming trends accompany long-term climate change, greater exposure times to seasonal allergens may occur with subsequent effects on public health.	34	118	2011	4	10.1073/pnas.1014107108	Science & Technology - Other Topics
Understanding patient sensitization profiles in complex pollen areas: a molecular epidemiological study. Background: Allergy diagnosis in patients exposed to multiple pollen species is complex and misdiagnosis is often a cause for unsuccessful specific immunotherapy. Objective: We studied the sensitization profile of individual allergens (major, minor and pan-allergens) in pollen-sensitized patients in a region with high exposure to olive pollen by investigating the influence of minor allergens on allergic disease and the association between pan- and minor allergen sensitizations. Methods: A panel of 13 purified allergens, which included the most relevant allergens in the area, as well as minor olive allergens and pan-allergens, were screened using a high-capacity technology (ADVIA-Centaur((R))) in 891 patients. Results: Olive allergy as measured by specific IgE to Ole e 1 was the leading pollinosis in the area. The minor olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin sensitization was associated mainly with grass allergy, the second most prevalent pollinosis. Salsola kali pollen allergy was the third most common cause of pollinosis in the area. The prevalence of sensitization to the peach allergen Pru p 3, a nonspecific lipid-transfer protein, was notable. Conclusion: Epidemiological analysis by component-resolved diagnosis is a new method, which elucidates the interaction between allergen exposure gradient and patient sensitization. High exposure leads to differential sensitization profiles some of which are associated with more severe allergic conditions. Profilin sensitization, related mainly to grass pollinosis, was a marker of more severe grass pollen sensitization.. allergens| environment| epidemiology| food allergens| pollen|olea-europaea pollen| cross-reactivity| relevant allergens| major allergens| purification| expression| marker| nomenclature| patterns| ole-e-1.	NOV-2008	allergens| environment| epidemiology| food allergens| pollen|olea-europaea pollen| cross-reactivity| relevant allergens| major allergens| purification| expression| marker| nomenclature| patterns| ole-e-1	Barber, D; de la Torre, F; Feo, F; Florido, F; Guardia, P; Moreno, C; Quiralte, J; Lombardero, M; Villalba, M; Salcedo, G; Rodriguez, R	Understanding patient sensitization profiles in complex pollen areas: a molecular epidemiological study		ALLERGY	allergens; environment; epidemiology; food allergens; pollen	OLEA-EUROPAEA POLLEN; CROSS-REACTIVITY; RELEVANT ALLERGENS; MAJOR ALLERGENS; PURIFICATION; EXPRESSION; MARKER; NOMENCLATURE; PATTERNS; OLE-E-1	Background: Allergy diagnosis in patients exposed to multiple pollen species is complex and misdiagnosis is often a cause for unsuccessful specific immunotherapy. Objective: We studied the sensitization profile of individual allergens (major, minor and pan-allergens) in pollen-sensitized patients in a region with high exposure to olive pollen by investigating the influence of minor allergens on allergic disease and the association between pan- and minor allergen sensitizations. Methods: A panel of 13 purified allergens, which included the most relevant allergens in the area, as well as minor olive allergens and pan-allergens, were screened using a high-capacity technology (ADVIA-Centaur((R))) in 891 patients. Results: Olive allergy as measured by specific IgE to Ole e 1 was the leading pollinosis in the area. The minor olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin sensitization was associated mainly with grass allergy, the second most prevalent pollinosis. Salsola kali pollen allergy was the third most common cause of pollinosis in the area. The prevalence of sensitization to the peach allergen Pru p 3, a nonspecific lipid-transfer protein, was notable. Conclusion: Epidemiological analysis by component-resolved diagnosis is a new method, which elucidates the interaction between allergen exposure gradient and patient sensitization. High exposure leads to differential sensitization profiles some of which are associated with more severe allergic conditions. Profilin sensitization, related mainly to grass pollinosis, was a marker of more severe grass pollen sensitization.	35	118	2008	9	10.1111/j.1398-9995.2008.01807.x	Allergy; Immunology
The unpleasantness of perceived dyspnea is processed in the anterior insula and amygdala. Rationale: The subjective perception of dyspnea, which is an impairing symptom in various cardiopulmonary diseases, consists of sensory (intensity) and affective aspects (unpleasantness). However, little is known about the cortical processing of the perception of dyspnea. Objectives: To investigate the cortical areas associated with the processing of the affective unpleasantness of perceived dyspnea. Methods: Brain imaging study using functional magnetic resonance imaging in 14 healthy volunteers. Measurements and Main Results: Dyspnea was induced by inspiratory resistive loaded breathing with concomitant positive and negative emotional stimulation by viewing standardized emotional picture series. The blood oxygen level-dependent contrast was measured as an index of local neuronal activity while respiration was continuously monitored. Negative emotional stimulation during loaded breathing was associated with higher unpleasantness of perceived dyspnea when compared with loaded breathing with concomitant positive emotional stimulation (P < 0.05). The levels of intensity of perceived dyspnea, respiratory responses, and load magnitude were similar between both conditions. Higher unpleasantness of dyspnea was associated with neuronal activations in the limbic system-that is, in the right anterior insula and in the right amygdala (respective Z values = 3.93 and 3.15; P < 0.05). Conclusions: The results of the present brain imaging study suggest that the unpleasantness of subjectively perceived dyspnea is processed in the right human anterior insula and amygdala.. brain| dyspnea| emotions| magnetic resonance imaging| perception|obstructive pulmonary-disease| positron-emission-tomography| affective dimension| interoceptive awareness| air hunger| brain| pain| perception| exercise| asthma.	MAY 1-2008	brain| dyspnea| emotions| magnetic resonance imaging| perception|obstructive pulmonary-disease| positron-emission-tomography| affective dimension| interoceptive awareness| air hunger| brain| pain| perception| exercise| asthma	von Leupoldt, A; Sommer, T; Kegat, S; Baumann, HJ; Klose, H; Dahme, B; Buchel, C	The unpleasantness of perceived dyspnea is processed in the anterior insula and amygdala		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	brain; dyspnea; emotions; magnetic resonance imaging; perception	OBSTRUCTIVE PULMONARY-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; AFFECTIVE DIMENSION; INTEROCEPTIVE AWARENESS; AIR HUNGER; BRAIN; PAIN; PERCEPTION; EXERCISE; ASTHMA	Rationale: The subjective perception of dyspnea, which is an impairing symptom in various cardiopulmonary diseases, consists of sensory (intensity) and affective aspects (unpleasantness). However, little is known about the cortical processing of the perception of dyspnea. Objectives: To investigate the cortical areas associated with the processing of the affective unpleasantness of perceived dyspnea. Methods: Brain imaging study using functional magnetic resonance imaging in 14 healthy volunteers. Measurements and Main Results: Dyspnea was induced by inspiratory resistive loaded breathing with concomitant positive and negative emotional stimulation by viewing standardized emotional picture series. The blood oxygen level-dependent contrast was measured as an index of local neuronal activity while respiration was continuously monitored. Negative emotional stimulation during loaded breathing was associated with higher unpleasantness of perceived dyspnea when compared with loaded breathing with concomitant positive emotional stimulation (P < 0.05). The levels of intensity of perceived dyspnea, respiratory responses, and load magnitude were similar between both conditions. Higher unpleasantness of dyspnea was associated with neuronal activations in the limbic system-that is, in the right anterior insula and in the right amygdala (respective Z values = 3.93 and 3.15; P < 0.05). Conclusions: The results of the present brain imaging study suggest that the unpleasantness of subjectively perceived dyspnea is processed in the right human anterior insula and amygdala.	53	118	2008	7	10.1164/rccm.200712-18210C	General & Internal Medicine; Respiratory System
Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: A randomized, double-blind, placebo-controlled study. Background: Atopic dermatitis often has an allergic component, and immunotherapy may therefore prove beneficial. Objective: To assess the effect of sublingual immunotherapy (SLIT) in children with atopic dermatitis. Methods: Children age 5 to 16 years with atopic dermatitis (Scoring Atopic Dermatitis [SCORAD] > 7) and sensitization to dust mites alone, without food allergy or chronic asthma, were enrolled in a randomized, double-blind, placebo-controlled study and stratified according to disease severity. SLIT or placebo was given for 18 months in addition to standard therapy. SCORAD, visual analog scale, and rescue medication consumption were recorded at 3-month intervals. Results: Fifty-six children were enrolled, and 28 were allocated to SLIT. Forty-eight completed the study, with 2 dropouts in the active and 6 in the placebo group. The difference from baseline in the SCORAD was significant (P = .025) between the 2 groups starting from month 9. Similarly, there was a significant reduction in the use of medications only in the active group. A trend toward significance was seen for the visual analog score only in the active group versus baseline (P = .07). A significant difference in the considered parameters was found only in patients with a mild-moderate disease, whereas severe patients had only a marginal benefit. SLIT had to be discontinued in 2 patients because of exacerbation of dermatitis. Conclusion: Sublingual immunotherapy to dust mite improves mild-moderate atopic dermatitis. Clinical implications: Sublingual immunotherapy may represent an additional therapeutic tool for the treatment of extrinsic atopic dermatitis in properly selected children.. atopic dermatitis| house dust mites| sublingual immunotherapy|allergic rhinitis| consensus report| efficacy| asthma| standardization| multicenter| trials.	JUL-2007	atopic dermatitis| house dust mites| sublingual immunotherapy|allergic rhinitis| consensus report| efficacy| asthma| standardization| multicenter| trials	Pajno, GB; Caminiti, L; Vita, D; Barberio, G; Salzano, G; Lombardo, F; Canonica, GW; Passalacqua, G	Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: A randomized, double-blind, placebo-controlled study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopic dermatitis; house dust mites; sublingual immunotherapy	ALLERGIC RHINITIS; CONSENSUS REPORT; EFFICACY; ASTHMA; STANDARDIZATION; MULTICENTER; TRIALS	Background: Atopic dermatitis often has an allergic component, and immunotherapy may therefore prove beneficial. Objective: To assess the effect of sublingual immunotherapy (SLIT) in children with atopic dermatitis. Methods: Children age 5 to 16 years with atopic dermatitis (Scoring Atopic Dermatitis [SCORAD] > 7) and sensitization to dust mites alone, without food allergy or chronic asthma, were enrolled in a randomized, double-blind, placebo-controlled study and stratified according to disease severity. SLIT or placebo was given for 18 months in addition to standard therapy. SCORAD, visual analog scale, and rescue medication consumption were recorded at 3-month intervals. Results: Fifty-six children were enrolled, and 28 were allocated to SLIT. Forty-eight completed the study, with 2 dropouts in the active and 6 in the placebo group. The difference from baseline in the SCORAD was significant (P = .025) between the 2 groups starting from month 9. Similarly, there was a significant reduction in the use of medications only in the active group. A trend toward significance was seen for the visual analog score only in the active group versus baseline (P = .07). A significant difference in the considered parameters was found only in patients with a mild-moderate disease, whereas severe patients had only a marginal benefit. SLIT had to be discontinued in 2 patients because of exacerbation of dermatitis. Conclusion: Sublingual immunotherapy to dust mite improves mild-moderate atopic dermatitis. Clinical implications: Sublingual immunotherapy may represent an additional therapeutic tool for the treatment of extrinsic atopic dermatitis in properly selected children.	30	118	2007	7	10.1016/j.jaci.2007.04.008	Allergy; Immunology
Maternal fish intake during pregnancy and atopy and asthma in infancy. Background: There is growing evidence that n-3 fatty acids have anti-inflammatory properties and may modulate immune response. Dietary intake of these nutrients during pregnancy could play a role in the risk of asthma and atopy in the offspring. Methods: Using data from a cohort of women (n=462) enrolled during pregnancy and whose offspring were followed up to 6 years, we evaluated the impact of fish consumption during pregnancy on the incidence of atopy and asthma. Dietary intake was assessed by food frequency questionnaire (42 items) applied by an interviewer. Results: Thirty-four percent of infants had a medical diagnosis of eczema at age 1 year, 14.3% of the children were atopic [based on skin prick test (SPT) at 6 years], and 5.7% had atopic wheeze at age 6 years. After adjusting for potential confounding factors, fish intake during pregnancy was protective against the risk of eczema at age 1 year, a positive SPT for house dust mite at age 6 years and atopic wheeze at age 6 years [odds ratio (OR)=0.73 95% confidence interval (CI) 0.55-0.98, OR=0.68, 95% CI 0.46-1.01 and OR=0.55, 95% CI 0.31-0.96, respectively]. For an increase in fish intake from once per week to 2.5 times per week, the risk of eczema at age 1 year decreased by 37%, and the risk of positive SPT at age 6 years by 35%. Stratification by breastfeeding showed that fish intake was significantly related to a decrease risk in persistent wheeze among non-breastfed children (P for interaction < 0.05). No protective effect was observed among breastfed children. Conclusion: Our data suggest a protective effect of fish intake during pregnancy on the risk of atopy-related outcomes.. asthma| atopy| children| fish intake| n-3 pufa| pregnancy|polyunsaturated fatty-acids| oil supplementation| allergic disease| immunoglobulin-a| controlled-trial| high-risk| childhood| consumption| responses| life.	APR-2007	asthma| atopy| children| fish intake| n-3 pufa| pregnancy|polyunsaturated fatty-acids| oil supplementation| allergic disease| immunoglobulin-a| controlled-trial| high-risk| childhood| consumption| responses| life	Romieu, I; Torrent, M; Garcia-Esteban, R; Ferrer, C; Ribas-Fito, N; Anto, JM; Sunyer, J	Maternal fish intake during pregnancy and atopy and asthma in infancy		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; atopy; children; fish intake; n-3 PUFA; pregnancy	POLYUNSATURATED FATTY-ACIDS; OIL SUPPLEMENTATION; ALLERGIC DISEASE; IMMUNOGLOBULIN-A; CONTROLLED-TRIAL; HIGH-RISK; CHILDHOOD; CONSUMPTION; RESPONSES; LIFE	Background: There is growing evidence that n-3 fatty acids have anti-inflammatory properties and may modulate immune response. Dietary intake of these nutrients during pregnancy could play a role in the risk of asthma and atopy in the offspring. Methods: Using data from a cohort of women (n=462) enrolled during pregnancy and whose offspring were followed up to 6 years, we evaluated the impact of fish consumption during pregnancy on the incidence of atopy and asthma. Dietary intake was assessed by food frequency questionnaire (42 items) applied by an interviewer. Results: Thirty-four percent of infants had a medical diagnosis of eczema at age 1 year, 14.3% of the children were atopic [based on skin prick test (SPT) at 6 years], and 5.7% had atopic wheeze at age 6 years. After adjusting for potential confounding factors, fish intake during pregnancy was protective against the risk of eczema at age 1 year, a positive SPT for house dust mite at age 6 years and atopic wheeze at age 6 years [odds ratio (OR)=0.73 95% confidence interval (CI) 0.55-0.98, OR=0.68, 95% CI 0.46-1.01 and OR=0.55, 95% CI 0.31-0.96, respectively]. For an increase in fish intake from once per week to 2.5 times per week, the risk of eczema at age 1 year decreased by 37%, and the risk of positive SPT at age 6 years by 35%. Stratification by breastfeeding showed that fish intake was significantly related to a decrease risk in persistent wheeze among non-breastfed children (P for interaction < 0.05). No protective effect was observed among breastfed children. Conclusion: Our data suggest a protective effect of fish intake during pregnancy on the risk of atopy-related outcomes.	33	118	2007	8	10.1111/j.1365-2222.2007.02685.x	Allergy; Immunology
Intestinal helminths protect in a murine model of asthma. Underdeveloped nations are relatively protected from the worldwide asthma epidemic; the hygiene hypothesis suggests this is due to suppression of Th2-mediated inflammation by increased exposure to pathogens and their products. Although microbial exposures can promote Th2-suppressing Th1 responses, even Th2-skewing infections, such as helminths, appear to suppress atopy, suggesting an alternate explanation for these observations. To investigate whether induction of regulatory responses by helminths may counter allergic inflammation, we examined the effects of helminth infection in a murine model of atopic asthma. We chose Heligosomoides polygyrus, a gastrointestinal nematode, as the experimental helminth; this worm does not enter the lung in its life cycle. We found that H. polygyrus infection suppressed allergen-induced airway eosinophilia, bronchial hyperreactivity, and in vitro allergen-recall Th2 responses in an IL-10-dependent manner; total and OVA-specific IgE, however, were increased by worm infection. Finally, helminth-infected mice were protected against eosinophilic inflammation induced by adoptive transfer of OVA-stimulated CD4(+) cells, and transfer of cells from helminth-infected/OVA-exposed mice suppressed OVA-induced eosinophilic inflammation, suggesting a role for regulatory cells. Increased CD4(+)CD25(+)Foxp3(+) cells were found in thoracic lymph nodes of helminth-infected/OVA-exposed mice. Helminthic colonization appears to protect against asthma and atopic disorders; the regulatory cytokine, IL-10, may be a critical player.. regulatory t-cells| induced airway inflammation| cytokine production| interleukin-10-deficient mice| cpg oligodeoxynucleotides| allergic sensitization| inverse association| hygiene hypothesis| th2 responses| hay-fever.	AUG 1-2006	regulatory t-cells| induced airway inflammation| cytokine production| interleukin-10-deficient mice| cpg oligodeoxynucleotides| allergic sensitization| inverse association| hygiene hypothesis| th2 responses| hay-fever	Kitagaki, K; Businga, TR; Racila, D; Elliott, DE; Weinstock, JV; Kline, JN	Intestinal helminths protect in a murine model of asthma		JOURNAL OF IMMUNOLOGY		REGULATORY T-CELLS; INDUCED AIRWAY INFLAMMATION; CYTOKINE PRODUCTION; INTERLEUKIN-10-DEFICIENT MICE; CPG OLIGODEOXYNUCLEOTIDES; ALLERGIC SENSITIZATION; INVERSE ASSOCIATION; HYGIENE HYPOTHESIS; TH2 RESPONSES; HAY-FEVER	Underdeveloped nations are relatively protected from the worldwide asthma epidemic; the hygiene hypothesis suggests this is due to suppression of Th2-mediated inflammation by increased exposure to pathogens and their products. Although microbial exposures can promote Th2-suppressing Th1 responses, even Th2-skewing infections, such as helminths, appear to suppress atopy, suggesting an alternate explanation for these observations. To investigate whether induction of regulatory responses by helminths may counter allergic inflammation, we examined the effects of helminth infection in a murine model of atopic asthma. We chose Heligosomoides polygyrus, a gastrointestinal nematode, as the experimental helminth; this worm does not enter the lung in its life cycle. We found that H. polygyrus infection suppressed allergen-induced airway eosinophilia, bronchial hyperreactivity, and in vitro allergen-recall Th2 responses in an IL-10-dependent manner; total and OVA-specific IgE, however, were increased by worm infection. Finally, helminth-infected mice were protected against eosinophilic inflammation induced by adoptive transfer of OVA-stimulated CD4(+) cells, and transfer of cells from helminth-infected/OVA-exposed mice suppressed OVA-induced eosinophilic inflammation, suggesting a role for regulatory cells. Increased CD4(+)CD25(+)Foxp3(+) cells were found in thoracic lymph nodes of helminth-infected/OVA-exposed mice. Helminthic colonization appears to protect against asthma and atopic disorders; the regulatory cytokine, IL-10, may be a critical player.	50	118	2006	8		Immunology
Clinical phenotypes of asthma. Purpose of review Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic mechanisms, but in particular to ascertain the specific genes associated with these phenotypes. Recent findings In children, three asthma phenotypes are now well defined: transient infant wheezing, nonatopic wheezing of the toddler, and IgE-mediated wheezing/asthma. Recently, a fourth phenotype, late-onset childhood asthma has been added to this list. In adults, asthma persisting from childhood into adulthood should be distinguished from asthma starting in adulthood. The phenotypes of adult-onset asthma are still poorly defined. Until now, phenotypic classification has been based primarily on etiologic factors (eg, aspirin sensitivity, persistent respiratory infections, occupational factors, or toxic exposures) or clinical characteristics of the disease (eg, mild, severe, brittle, near fatal, with fixed airflow obstruction, steroid resistant). Novel noninvasive techniques to assess the type and severity of airway inflammation and dysfunction are increasingly used to identify better the different phenotypes. Summary The classic phenotype of IgE-mediated asthma starting in childhood is now clearly defined. However, many other phenotypes of asthma in childhood as well in adulthood are being recognized. In particular, asthma starting in adulthood and noneosinophilic asthma constitute an important part of the adult asthma population, and are,still poorly defined. A precise definition of these asthma phenotypes is urgently needed because they are likely to be associated with different genotypes, responses to treatment, and prognoses.. phenotypes| childhood asthma| adult-onset asthma| severe asthma|aspirin-induced asthma| adult-onset asthma| near-fatal asthma| air-flow limitation| chlamydia-pneumoniae| occupational asthma| risk-factors| follow-up| bronchial responsiveness| allergic sensitization.	JAN-2004	phenotypes| childhood asthma| adult-onset asthma| severe asthma|aspirin-induced asthma| adult-onset asthma| near-fatal asthma| air-flow limitation| chlamydia-pneumoniae| occupational asthma| risk-factors| follow-up| bronchial responsiveness| allergic sensitization	Bel, EH	Clinical phenotypes of asthma		CURRENT OPINION IN PULMONARY MEDICINE	phenotypes; childhood asthma; adult-onset asthma; severe asthma	ASPIRIN-INDUCED ASTHMA; ADULT-ONSET ASTHMA; NEAR-FATAL ASTHMA; AIR-FLOW LIMITATION; CHLAMYDIA-PNEUMONIAE; OCCUPATIONAL ASTHMA; RISK-FACTORS; FOLLOW-UP; BRONCHIAL RESPONSIVENESS; ALLERGIC SENSITIZATION	Purpose of review Asthma is a phenotypically heterogeneous disorder and, over the years, many different clinical subtypes of asthma have been described. A precise definition of asthma phenotypes is now becoming more and more important, not only for a better understanding of pathophysiologic mechanisms, but in particular to ascertain the specific genes associated with these phenotypes. Recent findings In children, three asthma phenotypes are now well defined: transient infant wheezing, nonatopic wheezing of the toddler, and IgE-mediated wheezing/asthma. Recently, a fourth phenotype, late-onset childhood asthma has been added to this list. In adults, asthma persisting from childhood into adulthood should be distinguished from asthma starting in adulthood. The phenotypes of adult-onset asthma are still poorly defined. Until now, phenotypic classification has been based primarily on etiologic factors (eg, aspirin sensitivity, persistent respiratory infections, occupational factors, or toxic exposures) or clinical characteristics of the disease (eg, mild, severe, brittle, near fatal, with fixed airflow obstruction, steroid resistant). Novel noninvasive techniques to assess the type and severity of airway inflammation and dysfunction are increasingly used to identify better the different phenotypes. Summary The classic phenotype of IgE-mediated asthma starting in childhood is now clearly defined. However, many other phenotypes of asthma in childhood as well in adulthood are being recognized. In particular, asthma starting in adulthood and noneosinophilic asthma constitute an important part of the adult asthma population, and are,still poorly defined. A precise definition of these asthma phenotypes is urgently needed because they are likely to be associated with different genotypes, responses to treatment, and prognoses.	76	118	2004	7	10.1097/00063198-200401000-00008	Respiratory System
Asthma symptoms in Hispanic children and daily ambient exposures to toxic and criteria air pollutants. Although acute adverse effects on asthma have been frequently found for the U.S. Environmental Protection Agency's principal criteria air pollutants, there is little epidemiologic information on specific hydrocarbons from toxic emission sources. We conducted a panel study of 22 Hispanic children with asthma who were 10-16 years old and living in a Los Angeles community with high traffic density. Subjects filled out symptom diaries daily for up to 3 months (November 1999 through January 2000). Pollutants included ambient hourly values of ozone, nitrogen dioxide, Sulfur dioxide, and carbon monoxide and 24-hr values of volatile organic compounds (VOCs), particulate matter with aerodynamic diameter <10 &mu;m (PM10), and elemental carbon (EC) and organic carbon (OC) PM10 fractions. Asthma symptom severity was regressed on pollutants using generalized estimating equations, and peak expiratory flow (PEF) was regressed on pollutants using mixed models. We found positive associations of symptoms with criteria air pollutants (O-3, NO2, SO2, PM10),, EC-OC, and VOCs (benzene, ethylbenzene, formaldehyde, acetaldehyde, acetone, 1,3-butadiene, tetrachloroethylene, toluene, m,p-xylene, and o-xylene). Selected adjusted odds ratios for bothersome or more severe asthma symptoms from interquartile range increases in pollutants were, for 1.4 ppb 8-hr NO2, 1.27 [95% confidence interval (Cl), 1.05-1-54]; 1.00 ppb benzene, 1.23 (95% Cl, 1.02-1.48); 3.16 ppb formaldehyde, 1.37 (95% CI, 1.04-1.80); 37 &mu;g/m(3) PM,0, 1.45 (95% Cl, 1.11-1.90); 2.91 &mu;g/m(3) EC, 1.85 (95% Cl, 1.11-3.08); and 4.64 &mu;g/m(3) OC, 1.88 (95% CI, 1.12-3.17). Two-pollutant models of EC or OC with PM10 showed little change in odds ratios for EC (to 1.83) or OC (to 1.89), but PM10 decreased from 1.45 to 1.0. There were no significant associations with PEF. Findings support the view that air toxics in the pollutant mix from traffic and industrial sources may have adverse effects on asthma in children.. environmental air pollutants| hydrocarbons| longitudinal studies| nitrogen dioxide| ozone| statistical models| sulfur dioxide| vehicle emissions|peak expiratory flow| volatile organic-compounds| antiinflammatory medication use| inner-city children| respiratory health| ultrafine particles| formaldehyde exposure| fine particles| lung-function| los-angeles.	APR-2003	environmental air pollutants| hydrocarbons| longitudinal studies| nitrogen dioxide| ozone| statistical models| sulfur dioxide| vehicle emissions|peak expiratory flow| volatile organic-compounds| antiinflammatory medication use| inner-city children| respiratory health| ultrafine particles| formaldehyde exposure| fine particles| lung-function| los-angeles	Delfino, RJ; Gong, H; Linn, WS; Pellizzari, ED; Hu, Y	Asthma symptoms in Hispanic children and daily ambient exposures to toxic and criteria air pollutants		ENVIRONMENTAL HEALTH PERSPECTIVES	environmental air pollutants; hydrocarbons; longitudinal studies; nitrogen dioxide; ozone; statistical models; sulfur dioxide; vehicle emissions	PEAK EXPIRATORY FLOW; VOLATILE ORGANIC-COMPOUNDS; ANTIINFLAMMATORY MEDICATION USE; INNER-CITY CHILDREN; RESPIRATORY HEALTH; ULTRAFINE PARTICLES; FORMALDEHYDE EXPOSURE; FINE PARTICLES; LUNG-FUNCTION; LOS-ANGELES	Although acute adverse effects on asthma have been frequently found for the U.S. Environmental Protection Agency's principal criteria air pollutants, there is little epidemiologic information on specific hydrocarbons from toxic emission sources. We conducted a panel study of 22 Hispanic children with asthma who were 10-16 years old and living in a Los Angeles community with high traffic density. Subjects filled out symptom diaries daily for up to 3 months (November 1999 through January 2000). Pollutants included ambient hourly values of ozone, nitrogen dioxide, Sulfur dioxide, and carbon monoxide and 24-hr values of volatile organic compounds (VOCs), particulate matter with aerodynamic diameter <10 &mu;m (PM10), and elemental carbon (EC) and organic carbon (OC) PM10 fractions. Asthma symptom severity was regressed on pollutants using generalized estimating equations, and peak expiratory flow (PEF) was regressed on pollutants using mixed models. We found positive associations of symptoms with criteria air pollutants (O-3, NO2, SO2, PM10),, EC-OC, and VOCs (benzene, ethylbenzene, formaldehyde, acetaldehyde, acetone, 1,3-butadiene, tetrachloroethylene, toluene, m,p-xylene, and o-xylene). Selected adjusted odds ratios for bothersome or more severe asthma symptoms from interquartile range increases in pollutants were, for 1.4 ppb 8-hr NO2, 1.27 [95% confidence interval (Cl), 1.05-1-54]; 1.00 ppb benzene, 1.23 (95% Cl, 1.02-1.48); 3.16 ppb formaldehyde, 1.37 (95% CI, 1.04-1.80); 37 &mu;g/m(3) PM,0, 1.45 (95% Cl, 1.11-1.90); 2.91 &mu;g/m(3) EC, 1.85 (95% Cl, 1.11-3.08); and 4.64 &mu;g/m(3) OC, 1.88 (95% CI, 1.12-3.17). Two-pollutant models of EC or OC with PM10 showed little change in odds ratios for EC (to 1.83) or OC (to 1.89), but PM10 decreased from 1.45 to 1.0. There were no significant associations with PEF. Findings support the view that air toxics in the pollutant mix from traffic and industrial sources may have adverse effects on asthma in children.	66	118	2003	10	10.1289/ehp.5992	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
A longitudinal analysis of wheezing in young children: The independent effects of early life exposure to house dust endotoxin, allergens, and pets. Background: It has been postulated that exposure to bacterial endotoxins and animals early in life might confer protection against the development of asthma and allergies. Objective: We investigated the longitudinal effects of exposure to house dust endotoxin (HDE), allergen levels, and the presence of a dog in the home on wheezing in young children over a 4-year period. Methods: Two hundred twenty-six children younger than 5 years were followed for 4 years. Endotoxin and allergen levels were measured from house dust collected at baseline. Longitudinal associations were investigated by using a proportional hazards technique that allowed for multiple outcomes per subject. Results: Exposure to high concentrations of HDE of greater than the median level was associated with an increased risk for wheezing over the period of observation (multivariate relative risk, 1.52; 95% CI, 1.07-2.14), but this risk rapidly decreased over time (P for trend = .005). Exposure to cockroach allergen was associated with increased risk for wheezing, whereas exposure to cat allergen and the presence of a dog in the home were both associated with decreased risk for wheezing. The risks associated with cockroach allergen, cat allergen, and dog did not change over the period of observation. Conclusion: The negative associations between exposures to dogs and cat allergen and wheeze appear to be independent of the effects of endotoxin and suggest that separate mechanisms might mediate the effects of HDE exposure and pet exposure on the developing immune system.. endotoxin| allergens| domestic animals| wheeze| asthma|hay-fever| asthma| risk| sensitization| atopy| inhalation| community| decreases| cockroach| responses.	NOV-2002	endotoxin| allergens| domestic animals| wheeze| asthma|hay-fever| asthma| risk| sensitization| atopy| inhalation| community| decreases| cockroach| responses	Litonjua, AA; Milton, DK; Celedon, JC; Ryan, L; Weiss, ST; Gold, DR	A longitudinal analysis of wheezing in young children: The independent effects of early life exposure to house dust endotoxin, allergens, and pets		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	endotoxin; allergens; domestic animals; wheeze; asthma	HAY-FEVER; ASTHMA; RISK; SENSITIZATION; ATOPY; INHALATION; COMMUNITY; DECREASES; COCKROACH; RESPONSES	Background: It has been postulated that exposure to bacterial endotoxins and animals early in life might confer protection against the development of asthma and allergies. Objective: We investigated the longitudinal effects of exposure to house dust endotoxin (HDE), allergen levels, and the presence of a dog in the home on wheezing in young children over a 4-year period. Methods: Two hundred twenty-six children younger than 5 years were followed for 4 years. Endotoxin and allergen levels were measured from house dust collected at baseline. Longitudinal associations were investigated by using a proportional hazards technique that allowed for multiple outcomes per subject. Results: Exposure to high concentrations of HDE of greater than the median level was associated with an increased risk for wheezing over the period of observation (multivariate relative risk, 1.52; 95% CI, 1.07-2.14), but this risk rapidly decreased over time (P for trend = .005). Exposure to cockroach allergen was associated with increased risk for wheezing, whereas exposure to cat allergen and the presence of a dog in the home were both associated with decreased risk for wheezing. The risks associated with cockroach allergen, cat allergen, and dog did not change over the period of observation. Conclusion: The negative associations between exposures to dogs and cat allergen and wheeze appear to be independent of the effects of endotoxin and suggest that separate mechanisms might mediate the effects of HDE exposure and pet exposure on the developing immune system.	33	118	2002	7	10.1067/mai.2002.128948	Allergy; Immunology
Anti-apoptotic effect of cGMP in cultured astrocytes - Inhibition by cGMP-dependent protein kinase of mitochondrial permeable transition pore. Reperfusion of cultured astrocytes with normal medium after exposure to H2O2-containing medium causes apoptosis. We have recently shown that ibudilast, which has been used for bronchial asthma and cerebrovascular disorders, attenuated the H2O2-induced apoptosis of astrocytes via the cGMP signaling pathway. This study examines the mechanism underlying the protective effect of cGMP. The membrane-permeable cGMP analog dibutyryl-cGMP attenuated the H2O2-induced decrease in cell viability, DNA ladder formation, nuclear condensation, reduction of the mitochondrial membrane potential, cytochrome c release from mitochondria, and caspase-3 activation in cultured astrocytes. These effects of dibutyryl-cGMP were almost completely inhibited by the cGMP-dependent protein kinase (PKG) inhibitor KT5823. In isolated rat brain mitochondria, cGMP in the presence of cytosolic extract from astrocytes inhibited the mitochondrial permeability transition pore (PTP) as determined by monitoring Ca2+-induced mitochondrial swelling. This ability of the cytosolic extract was inactivated by heat treatment and was mimicked by exogenous PKG. The effect of cGMP on the mitochondrial swelling was blocked by KT5823. The PTP inhibitors cyclosporin A and bongkrekic acid prevented the H2O2-induced decrease in cell viability and caspase-3 activation. These findings demonstrate that cGMP inhibits the mitochondrial PTP via the activation of PKG, and the prevention of mitochondrial dysfunction contributes to its anti-apoptotic effect.. programmed cell-death| cytochrome-c release| nitric-oxide| rat astrocytes| na+-ca2+ exchanger| reperfusion injury| cyclosporine-a| inner membrane| pc12 cells| activation.	DEC 21-2001	programmed cell-death| cytochrome-c release| nitric-oxide| rat astrocytes| na+-ca2+ exchanger| reperfusion injury| cyclosporine-a| inner membrane| pc12 cells| activation	Takuma, K; Phuagphong, P; Lee, E; Mori, K; Baba, A; Matsuda, T	Anti-apoptotic effect of cGMP in cultured astrocytes - Inhibition by cGMP-dependent protein kinase of mitochondrial permeable transition pore		JOURNAL OF BIOLOGICAL CHEMISTRY		PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; NITRIC-OXIDE; RAT ASTROCYTES; NA+-CA2+ EXCHANGER; REPERFUSION INJURY; CYCLOSPORINE-A; INNER MEMBRANE; PC12 CELLS; ACTIVATION	Reperfusion of cultured astrocytes with normal medium after exposure to H2O2-containing medium causes apoptosis. We have recently shown that ibudilast, which has been used for bronchial asthma and cerebrovascular disorders, attenuated the H2O2-induced apoptosis of astrocytes via the cGMP signaling pathway. This study examines the mechanism underlying the protective effect of cGMP. The membrane-permeable cGMP analog dibutyryl-cGMP attenuated the H2O2-induced decrease in cell viability, DNA ladder formation, nuclear condensation, reduction of the mitochondrial membrane potential, cytochrome c release from mitochondria, and caspase-3 activation in cultured astrocytes. These effects of dibutyryl-cGMP were almost completely inhibited by the cGMP-dependent protein kinase (PKG) inhibitor KT5823. In isolated rat brain mitochondria, cGMP in the presence of cytosolic extract from astrocytes inhibited the mitochondrial permeability transition pore (PTP) as determined by monitoring Ca2+-induced mitochondrial swelling. This ability of the cytosolic extract was inactivated by heat treatment and was mimicked by exogenous PKG. The effect of cGMP on the mitochondrial swelling was blocked by KT5823. The PTP inhibitors cyclosporin A and bongkrekic acid prevented the H2O2-induced decrease in cell viability and caspase-3 activation. These findings demonstrate that cGMP inhibits the mitochondrial PTP via the activation of PKG, and the prevention of mitochondrial dysfunction contributes to its anti-apoptotic effect.	44	118	2001	7	10.1074/jbc.M108622200	Biochemistry & Molecular Biology
Number concentration and size of particles in urban air: Effects on spirometric lung function in adult asthmatic subjects. Daily variations in ambient particulate air pollution are associated with variations in respiratory lung Function. It has been suggested that the effects of particulate matter may be due to particles in the ultrafine (0.01-0.1 mum) size range. Be-cause previous studies on ultrafine particles only used self-monitored peak expiratory now rate (PEFR), we assessed the associations between particle mars and number concentrations in several size ranges measured at a central site and measured (biweekly) spirometric lung function among a group of 54 adult asthmatics (n = 495 measurements). We also compared results to daily morning, afternoon, and evening PEFR measurements done at home (n = 7,672-8,110 measurements), The median (maximum) 24 hr number concentrations were 14,500/cm(3) (46,500/cm(3)) ultrafine particles and 800/cm(3) (2,800/cm3) accumulation mode (0.1-1 mum) particles. The median (maximum) mass concentration of PM2.5 (particulate matter <2.5 <mu>m) and PM10 (particulate matter <10 <mu>m in aerodynamic diameter) were 8.4 mug/m(3) (38.3 mug/m(3)) and 13.5 mug/m(3) (73.7 mug/m(3)), respectively. The number of accumulation mode particles was consistently inversely associated with PEFR in spirometry. Inverse, but nonsignificant, associations were observed with ultrafine particles, and no associations were observed with large particles (PM10). Compared to the effect estimates for self-monitored PEFR, the effect estimates for spirometric PEFR tended to be larger. The standard errors were also larger, probably due to the lower number of spirometric measurements. The present results support the need to monitor the particle number and size distributions in urban air in addition to mass.. air pollution| asthma| fvc| fev1| particles| particle size| peak expiratory flow rate| pefr| spirometry|respiratory health| ultrafine particles| cytokine production| fine particles| pollution| children| pm10| mortality| association| atmosphere.	APR-2001	air pollution| asthma| fvc| fev1| particles| particle size| peak expiratory flow rate| pefr| spirometry|respiratory health| ultrafine particles| cytokine production| fine particles| pollution| children| pm10| mortality| association| atmosphere	Penttinen, P; Timonen, KL; Tiittanen, P; Mirme, A; Ruuskanen, J; Pekkanen, J	Number concentration and size of particles in urban air: Effects on spirometric lung function in adult asthmatic subjects		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma; FVC; FEV1; particles; particle size; peak expiratory flow rate; PEFR; spirometry	RESPIRATORY HEALTH; ULTRAFINE PARTICLES; CYTOKINE PRODUCTION; FINE PARTICLES; POLLUTION; CHILDREN; PM10; MORTALITY; ASSOCIATION; ATMOSPHERE	Daily variations in ambient particulate air pollution are associated with variations in respiratory lung Function. It has been suggested that the effects of particulate matter may be due to particles in the ultrafine (0.01-0.1 mum) size range. Be-cause previous studies on ultrafine particles only used self-monitored peak expiratory now rate (PEFR), we assessed the associations between particle mars and number concentrations in several size ranges measured at a central site and measured (biweekly) spirometric lung function among a group of 54 adult asthmatics (n = 495 measurements). We also compared results to daily morning, afternoon, and evening PEFR measurements done at home (n = 7,672-8,110 measurements), The median (maximum) 24 hr number concentrations were 14,500/cm(3) (46,500/cm(3)) ultrafine particles and 800/cm(3) (2,800/cm3) accumulation mode (0.1-1 mum) particles. The median (maximum) mass concentration of PM2.5 (particulate matter <2.5 <mu>m) and PM10 (particulate matter <10 <mu>m in aerodynamic diameter) were 8.4 mug/m(3) (38.3 mug/m(3)) and 13.5 mug/m(3) (73.7 mug/m(3)), respectively. The number of accumulation mode particles was consistently inversely associated with PEFR in spirometry. Inverse, but nonsignificant, associations were observed with ultrafine particles, and no associations were observed with large particles (PM10). Compared to the effect estimates for self-monitored PEFR, the effect estimates for spirometric PEFR tended to be larger. The standard errors were also larger, probably due to the lower number of spirometric measurements. The present results support the need to monitor the particle number and size distributions in urban air in addition to mass.	29	118	2001	5	10.2307/3454889	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Airway responsiveness in early infancy predicts asthma, lung function, and respiratory symptoms by school age. Asthma is the most common chronic childhood disease in developed nations. Little is known about the relationship between airway responsiveness in infancy and the development of asthma later in life. The relationship of airway responsiveness at 1 mo with asthma, atopy, lower respiratory symptoms, and lung function at 6 yr of age was investigated prospectively in 95 white children from a randomly ascertained birth cohort. Baseline spirometry, airway responsiveness to histamine, and skin reactivity to common allergens were assessed at the age of 1 mo and 6 yr. Total serum immunoglobulin E (IgE) was measured from cord blood and at 6 yr. Brood eosinophil counts were measured at 6 yr only. Family, symptom, and exposure histories at both time points were derived from questionnaire data. Independently of the other factors assessed, increased airway responsiveness at 1 mo was significantly associated with the following parameters measured at six yr: decreased FEV1 (p < 0.001); decreased FVC (p < 0.001); physician-diagnosed asthma (p < 0.001); and lower respiratory tract symptoms (p < 0.05). None of the other physiologic factors measured in infancy showed such consistent associations with important clinical and physiologic outcomes at age 6. These data suggest that airway responsiveness in early life defines a functional state that is associated with abnormal airway function, lower respiratory symptoms, and the emergence of asthma by 6 yr of age.. bronchial hyperresponsiveness| subsequent development| early-childhood| family history| risk-factors| children| smoking| life| population| inflammation.	JAN-2001	bronchial hyperresponsiveness| subsequent development| early-childhood| family history| risk-factors| children| smoking| life| population| inflammation	Palmer, LJ; Rye, PJ; Gibson, NA; Burton, PR; Landau, LI; LeSouef, PN	Airway responsiveness in early infancy predicts asthma, lung function, and respiratory symptoms by school age		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		BRONCHIAL HYPERRESPONSIVENESS; SUBSEQUENT DEVELOPMENT; EARLY-CHILDHOOD; FAMILY HISTORY; RISK-FACTORS; CHILDREN; SMOKING; LIFE; POPULATION; INFLAMMATION	Asthma is the most common chronic childhood disease in developed nations. Little is known about the relationship between airway responsiveness in infancy and the development of asthma later in life. The relationship of airway responsiveness at 1 mo with asthma, atopy, lower respiratory symptoms, and lung function at 6 yr of age was investigated prospectively in 95 white children from a randomly ascertained birth cohort. Baseline spirometry, airway responsiveness to histamine, and skin reactivity to common allergens were assessed at the age of 1 mo and 6 yr. Total serum immunoglobulin E (IgE) was measured from cord blood and at 6 yr. Brood eosinophil counts were measured at 6 yr only. Family, symptom, and exposure histories at both time points were derived from questionnaire data. Independently of the other factors assessed, increased airway responsiveness at 1 mo was significantly associated with the following parameters measured at six yr: decreased FEV1 (p < 0.001); decreased FVC (p < 0.001); physician-diagnosed asthma (p < 0.001); and lower respiratory tract symptoms (p < 0.05). None of the other physiologic factors measured in infancy showed such consistent associations with important clinical and physiologic outcomes at age 6. These data suggest that airway responsiveness in early life defines a functional state that is associated with abnormal airway function, lower respiratory symptoms, and the emergence of asthma by 6 yr of age.	38	118	2001	6		General & Internal Medicine; Respiratory System
Long-term Ambient Fine Particulate Matter Air Pollution and Lung Cancer in a Large Cohort of Never-Smokers. Rationale: There is compelling evidence that acute and chronic exposure to ambient fine particulate matter (PM2.5) air pollution increases cardiopulmonary mortality. However, the role of PM2.5 in the etiology of lung cancer is less clear, particularly at concentrations that prevail in developed countries and in never-smokers. Objectives: This study examined the association between mean long-term ambient PM2.5 concentrations and lung cancer mortality among 188,699 lifelong never-smokers drawn from the nearly 1.2 million Cancer Prevention Study-II participants enrolled by the American Cancer Society in 1982 and followed prospectively through 2008. Methods: Mean metropolitan statistical area PM2.5 concentrations were determined for each participant based on central monitoring data. Cox proportional hazards regression models were used to estimate multivariate adjusted hazard ratios and 95% confidence intervals for lung cancer mortality in relation to PM2.5. Measurements and Main Results: A total of 1,100 lung cancer deaths were observed during the 26-year follow-up period. Each 10 mu g/m(3) increase in PM2.5 concentrations was associated with a 15-27% increase in lung cancer mortality. The association between PM2.5 and lung cancer mortality was similar in men and women and across categories of attained age and educational attainment, but was stronger in those with a normal body mass index and a history of chronic lung disease at enrollment (P < 0.05). Conclusions: The present findings strengthen the evidence that ambient concentrations of PM2.5 measured in recent decades are associated with small but measurable increases in lung cancer mortality.. fine particulate matter air pollution| lung neoplasms| never-smokers| asthma| pulmonary disease, chronic obstructive|obstructive pulmonary-disease| oxidative damage| health impacts| norwegian men| follow-up| mortality| risk| association| exposure| interventions.	DEC 15-2011	fine particulate matter air pollution| lung neoplasms| never-smokers| asthma| pulmonary disease, chronic obstructive|obstructive pulmonary-disease| oxidative damage| health impacts| norwegian men| follow-up| mortality| risk| association| exposure| interventions	Turner, MC; Krewski, D; Pope, CA; Chen, Y; Gapstur, SM; Thun, MJ	Long-term Ambient Fine Particulate Matter Air Pollution and Lung Cancer in a Large Cohort of Never-Smokers		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	fine particulate matter air pollution; lung neoplasms; never-smokers; asthma; pulmonary disease, chronic obstructive	OBSTRUCTIVE PULMONARY-DISEASE; OXIDATIVE DAMAGE; HEALTH IMPACTS; NORWEGIAN MEN; FOLLOW-UP; MORTALITY; RISK; ASSOCIATION; EXPOSURE; INTERVENTIONS	Rationale: There is compelling evidence that acute and chronic exposure to ambient fine particulate matter (PM2.5) air pollution increases cardiopulmonary mortality. However, the role of PM2.5 in the etiology of lung cancer is less clear, particularly at concentrations that prevail in developed countries and in never-smokers. Objectives: This study examined the association between mean long-term ambient PM2.5 concentrations and lung cancer mortality among 188,699 lifelong never-smokers drawn from the nearly 1.2 million Cancer Prevention Study-II participants enrolled by the American Cancer Society in 1982 and followed prospectively through 2008. Methods: Mean metropolitan statistical area PM2.5 concentrations were determined for each participant based on central monitoring data. Cox proportional hazards regression models were used to estimate multivariate adjusted hazard ratios and 95% confidence intervals for lung cancer mortality in relation to PM2.5. Measurements and Main Results: A total of 1,100 lung cancer deaths were observed during the 26-year follow-up period. Each 10 mu g/m(3) increase in PM2.5 concentrations was associated with a 15-27% increase in lung cancer mortality. The association between PM2.5 and lung cancer mortality was similar in men and women and across categories of attained age and educational attainment, but was stronger in those with a normal body mass index and a history of chronic lung disease at enrollment (P < 0.05). Conclusions: The present findings strengthen the evidence that ambient concentrations of PM2.5 measured in recent decades are associated with small but measurable increases in lung cancer mortality.	49	117	2011	8	10.1164/rccm.201106-1011OC	General & Internal Medicine; Respiratory System
Safety assessment of personal care products/cosmetics and their ingredients. We attempt to review the safety assessment of personal care products (PCP) and ingredients that are representative and pose complex safety issues. PCP are generally applied to human skin and mainly produce local exposure, although skin penetration or use in the oral cavity, on the face, lips, eyes and mucosa may also produce human systemic exposure. In the EU, US and Japan, the safety of PCP is regulated under cosmetic and/or drug regulations. Oxidative hair dyes contain arylamines, the most chemically reactive ingredients of PCP. Although arylamines have an allergic potential, taking into account the high number of consumers exposed, the incidence and prevalence of hair dye allergy appears to be low and stable. A recent (2001) epidemiology study suggested an association of oxidative hair dye use and increased bladder cancer risk in consumers, although this was not confirmed by subsequent or previous epidemiologic investigations. The results of genetic toxicity, carcinogenicity and reproductive toxicity studies Suggest that modern hair dyes and their ingredients pose no genotoxic, carcinogenic or reproductive risk. Recent reports suggest that arylamines contained in oxidative hair dyes are N-acetylated in human or mammalian skin resulting in systemic exposure to traces of detoxified, i.e. non-genotoxic, metabolites, whereas human hepatocytes were unable to transform hair dye arylamines to potentially carcinogenic metabolites. An expert panel of the International Agency on Research of Cancer (IARC) concluded that there is no evidence for a causal association of hair dye exposure with an elevated cancer risk in consumers. Ultraviolet filters have important benefits by protecting the consumer against adverse effects of UV radiation; these substances undergo a stringent safety evaluation under current international regulations prior to their marketing. Concerns were also raised about the safety of solid nanoparticles in PCP, mainly TiO(2) and ZnO in Sunscreens. However, current evidence suggests that these particles are non-toxic, do not penetrate into or through normal or compromised human skin and, therefore, pose no risk to human health. The increasing use of natural plant ingredients in personal care products raised new safety issues that require novel approaches to their safety evaluation similar to those of plant-derived food ingredients. For example, the Threshold of Toxicological Concern (TTC) is a promising tool to assess the safety of substances present at trace levels as well as minor ingredients of plant-derived substances. The potential human systemic exposure to PCP ingredients is increasingly estimated on the basis of in vitro skin penetration data. However, new evidence suggests that the in vitro test may overestimate human systemic exposure to PCP ingredients due to the absence of metabolism in cadaver skin or misclassification of skin residues that, in vivo, remain in the stratum corneum or hair follicle openings, i.e. outside the living skin. Overall, today's safety assessment of PCP and their ingredients is not only based on science, but also on their respective regulatory status as well as other issues, such as the ethics of animal testing. Nevertheless, the record shows that today's PCP are safe and offer multiple benefits to quality of life and health of the consumer. In the interest of all stakeholders, consumers, regulatory bodies and producers, there is an urgent need for an international harmonization on the status and safety requirements of these products and their ingredients. (C) 2009 Elsevier Inc. Al rights reserved.. safety assessment| personal care products| cosmetic ingredients| hair dyes| ultraviolet filters| threshold of toxicological concern| nanoparticles|permanent hair-dyes| vitro percutaneous-absorption| toxicological concern ttc| natural flavor complexes| bladder-cancer risk| human health-risk| para-phenylenediamine| in-vitro| aromatic-amines| stratum-corneum.	MAR 1-2010	safety assessment| personal care products| cosmetic ingredients| hair dyes| ultraviolet filters| threshold of toxicological concern| nanoparticles|permanent hair-dyes| vitro percutaneous-absorption| toxicological concern ttc| natural flavor complexes| bladder-cancer risk| human health-risk| para-phenylenediamine| in-vitro| aromatic-amines| stratum-corneum	Nohynek, GJ; Antignac, E; Re, T; Toutain, H	Safety assessment of personal care products/cosmetics and their ingredients		TOXICOLOGY AND APPLIED PHARMACOLOGY	Safety assessment; Personal care products; Cosmetic ingredients; Hair dyes; Ultraviolet filters; Threshold of toxicological concern; Nanoparticles	PERMANENT HAIR-DYES; VITRO PERCUTANEOUS-ABSORPTION; TOXICOLOGICAL CONCERN TTC; NATURAL FLAVOR COMPLEXES; BLADDER-CANCER RISK; HUMAN HEALTH-RISK; PARA-PHENYLENEDIAMINE; IN-VITRO; AROMATIC-AMINES; STRATUM-CORNEUM	We attempt to review the safety assessment of personal care products (PCP) and ingredients that are representative and pose complex safety issues. PCP are generally applied to human skin and mainly produce local exposure, although skin penetration or use in the oral cavity, on the face, lips, eyes and mucosa may also produce human systemic exposure. In the EU, US and Japan, the safety of PCP is regulated under cosmetic and/or drug regulations. Oxidative hair dyes contain arylamines, the most chemically reactive ingredients of PCP. Although arylamines have an allergic potential, taking into account the high number of consumers exposed, the incidence and prevalence of hair dye allergy appears to be low and stable. A recent (2001) epidemiology study suggested an association of oxidative hair dye use and increased bladder cancer risk in consumers, although this was not confirmed by subsequent or previous epidemiologic investigations. The results of genetic toxicity, carcinogenicity and reproductive toxicity studies Suggest that modern hair dyes and their ingredients pose no genotoxic, carcinogenic or reproductive risk. Recent reports suggest that arylamines contained in oxidative hair dyes are N-acetylated in human or mammalian skin resulting in systemic exposure to traces of detoxified, i.e. non-genotoxic, metabolites, whereas human hepatocytes were unable to transform hair dye arylamines to potentially carcinogenic metabolites. An expert panel of the International Agency on Research of Cancer (IARC) concluded that there is no evidence for a causal association of hair dye exposure with an elevated cancer risk in consumers. Ultraviolet filters have important benefits by protecting the consumer against adverse effects of UV radiation; these substances undergo a stringent safety evaluation under current international regulations prior to their marketing. Concerns were also raised about the safety of solid nanoparticles in PCP, mainly TiO(2) and ZnO in Sunscreens. However, current evidence suggests that these particles are non-toxic, do not penetrate into or through normal or compromised human skin and, therefore, pose no risk to human health. The increasing use of natural plant ingredients in personal care products raised new safety issues that require novel approaches to their safety evaluation similar to those of plant-derived food ingredients. For example, the Threshold of Toxicological Concern (TTC) is a promising tool to assess the safety of substances present at trace levels as well as minor ingredients of plant-derived substances. The potential human systemic exposure to PCP ingredients is increasingly estimated on the basis of in vitro skin penetration data. However, new evidence suggests that the in vitro test may overestimate human systemic exposure to PCP ingredients due to the absence of metabolism in cadaver skin or misclassification of skin residues that, in vivo, remain in the stratum corneum or hair follicle openings, i.e. outside the living skin. Overall, today's safety assessment of PCP and their ingredients is not only based on science, but also on their respective regulatory status as well as other issues, such as the ethics of animal testing. Nevertheless, the record shows that today's PCP are safe and offer multiple benefits to quality of life and health of the consumer. In the interest of all stakeholders, consumers, regulatory bodies and producers, there is an urgent need for an international harmonization on the status and safety requirements of these products and their ingredients. (C) 2009 Elsevier Inc. Al rights reserved.	184	117	2010	21	10.1016/j.taap.2009.12.001	Pharmacology & Pharmacy; Toxicology
A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis. Canine atopic dermatitis (CAD) is a multifaceted disease associated with exposure to various offending agents such as environmental and food allergens. The diagnosis of this condition is difficult because none of the typical signs are pathognomonic. Sets of criteria have been proposed but are mainly used to include dogs in clinical studies. The goals of the present study were to characterize the clinical features and signs of a large population of dogs with CAD, to identify which of these characteristics could be different in food-induced atopic dermatitis (FIAD) and non-food-induced atopic dermatitis (NFIAD) and to develop criteria for the diagnosis of this condition. Using simulated annealing, selected criteria were tested on a large and geographically widespread population of pruritic dogs. The study first described the signalment, history and clinical features of a large population of CAD dogs, compared FIAD and NFIAD dogs and confirmed that both conditions are clinically indistinguishable. Correlations of numerous clinical features with the diagnosis of CAD are subsequently calculated, and two sets of criteria associated with sensitivity and specificity ranging from 80% to 85% and from 79% to 85%, respectively, are proposed. It is finally demonstrated that these new sets of criteria provide better sensitivity and specificity, when compared to Willemse and Prelaud criteria. These criteria can be applied to both FIAD and NFIAD dogs.. acvd task-force| food sensitivity| criteria| dogs| allergy| manifestations| population| prevalence| validation| etiology.	FEB-2010	acvd task-force| food sensitivity| criteria| dogs| allergy| manifestations| population| prevalence| validation| etiology	Favrot, C; Steffan, J; Seewald, W; Picco, F	A prospective study on the clinical features of chronic canine atopic dermatitis and its diagnosis		VETERINARY DERMATOLOGY		ACVD TASK-FORCE; FOOD SENSITIVITY; CRITERIA; DOGS; ALLERGY; MANIFESTATIONS; POPULATION; PREVALENCE; VALIDATION; ETIOLOGY	Canine atopic dermatitis (CAD) is a multifaceted disease associated with exposure to various offending agents such as environmental and food allergens. The diagnosis of this condition is difficult because none of the typical signs are pathognomonic. Sets of criteria have been proposed but are mainly used to include dogs in clinical studies. The goals of the present study were to characterize the clinical features and signs of a large population of dogs with CAD, to identify which of these characteristics could be different in food-induced atopic dermatitis (FIAD) and non-food-induced atopic dermatitis (NFIAD) and to develop criteria for the diagnosis of this condition. Using simulated annealing, selected criteria were tested on a large and geographically widespread population of pruritic dogs. The study first described the signalment, history and clinical features of a large population of CAD dogs, compared FIAD and NFIAD dogs and confirmed that both conditions are clinically indistinguishable. Correlations of numerous clinical features with the diagnosis of CAD are subsequently calculated, and two sets of criteria associated with sensitivity and specificity ranging from 80% to 85% and from 79% to 85%, respectively, are proposed. It is finally demonstrated that these new sets of criteria provide better sensitivity and specificity, when compared to Willemse and Prelaud criteria. These criteria can be applied to both FIAD and NFIAD dogs.	33	117	2010	8	10.1111/j.1365-3164.2009.00758.x	Dermatology; Veterinary Sciences
Parental smoking and lung function in children - An international study. Rationale: Both prenatal and postnatal passive smoking have been linked with respiratory symptoms and asthma in childhood. Their differential contributions to lung function growth in the general children's population are less clear. Objective: To study the relative impact of pre- and postnatal exposure on respiratory functions of primary school children in a wide range of geographic settings, we analyzed flow and volume data of more than 20,000 children (aged 6-12 yr) from nine countries in Europe and North America. Methods: Exposure information had been obtained by comparable questionnaires, and spirometry followed a protocol of the American Thoracic Society/European Respiratory Society. Linear and logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytic tools. Main Results: Smoking during pregnancy was associated with decreases in lung function parameters between -1% (FEV1) and -6% maximal expiratory flow at 25% of vital capacity left (MEF25). A 4% lower maximal midexpiratory flow (MMEF) corresponded to a 40% increase in the risk of poor lung function (MMEF < 75% of expected). Associations with current passive smoking were weaker though still measurable, with effects ranging from -0.5% (FEV1) to -2% maximal expiratory flow (MEF50). Conclusions: Considering the high number of children exposed to maternal smoking in utero and the even higher number exposed to passive smoking after birth, this risk factor for reduced lung function growth remains a serious pediatric and public health issue.. child| passive smoking| pregnancy| spirometry| tobacco|environmental tobacco-smoke| maternal smoking| in-utero| respiratory symptoms| air-pollution| risk-factors| exposure| asthma| childhood| health.	JUN 1-2006	child| passive smoking| pregnancy| spirometry| tobacco|environmental tobacco-smoke| maternal smoking| in-utero| respiratory symptoms| air-pollution| risk-factors| exposure| asthma| childhood| health	Moshammer, H; Hoek, G; Luttmann-Gibson, H; Neuberger, MA; Antova, T; Gehring, U; Hruba, F; Pattenclen, S; Rudnai, P; Slachtova, H; Zlotkowska, R; Fletcher, T	Parental smoking and lung function in children - An international study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	child; passive smoking; pregnancy; spirometry; tobacco	ENVIRONMENTAL TOBACCO-SMOKE; MATERNAL SMOKING; IN-UTERO; RESPIRATORY SYMPTOMS; AIR-POLLUTION; RISK-FACTORS; EXPOSURE; ASTHMA; CHILDHOOD; HEALTH	Rationale: Both prenatal and postnatal passive smoking have been linked with respiratory symptoms and asthma in childhood. Their differential contributions to lung function growth in the general children's population are less clear. Objective: To study the relative impact of pre- and postnatal exposure on respiratory functions of primary school children in a wide range of geographic settings, we analyzed flow and volume data of more than 20,000 children (aged 6-12 yr) from nine countries in Europe and North America. Methods: Exposure information had been obtained by comparable questionnaires, and spirometry followed a protocol of the American Thoracic Society/European Respiratory Society. Linear and logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results and mean effects were estimated using meta-analytic tools. Main Results: Smoking during pregnancy was associated with decreases in lung function parameters between -1% (FEV1) and -6% maximal expiratory flow at 25% of vital capacity left (MEF25). A 4% lower maximal midexpiratory flow (MMEF) corresponded to a 40% increase in the risk of poor lung function (MMEF < 75% of expected). Associations with current passive smoking were weaker though still measurable, with effects ranging from -0.5% (FEV1) to -2% maximal expiratory flow (MEF50). Conclusions: Considering the high number of children exposed to maternal smoking in utero and the even higher number exposed to passive smoking after birth, this risk factor for reduced lung function growth remains a serious pediatric and public health issue.	34	117	2006	9	10.1164/rccm.200510-1552OC	General & Internal Medicine; Respiratory System
A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?. Background While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult. Objective A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods. Methods In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials. Results A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 mug of the allergenic food and would continue with doses of 100 mug and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose. Conclusion A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals.. allergy| clinical trial| dbpcfc| exposure| food| threshold| risk assessment|casein hydrolysate formula| double-blind| ige concentrations| atopic-dermatitis| peanut allergy| egg allergy| cow milk| challenges| hypersensitivity| identification.	MAY-2004	allergy| clinical trial| dbpcfc| exposure| food| threshold| risk assessment|casein hydrolysate formula| double-blind| ige concentrations| atopic-dermatitis| peanut allergy| egg allergy| cow milk| challenges| hypersensitivity| identification	Taylor, SL; Hefle, SL; Bindslev-Jensen, C; Atkins, FM; Andre, C; Bruijnzeel-Koomen, C; Burks, AW; Bush, RK; Ebisawa, M; Eigenmann, PA; Host, A; Hourihane, JO; Isolauri, E; Hill, DJ; Knulst, A; Lack, G; Sampson, HA; Moneret-Vautrin, DA; Rance, F; Vadas, PA; Yunginger, JW; Zeiger, RS; Salminen, JW; Madsen, C; Abbott, P	A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; clinical trial; DBPCFC; exposure; food; threshold; risk assessment	CASEIN HYDROLYSATE FORMULA; DOUBLE-BLIND; IGE CONCENTRATIONS; ATOPIC-DERMATITIS; PEANUT ALLERGY; EGG ALLERGY; COW MILK; CHALLENGES; HYPERSENSITIVITY; IDENTIFICATION	Background While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult. Objective A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods. Methods In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials. Results A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 mug of the allergenic food and would continue with doses of 100 mug and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose. Conclusion A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals.	33	117	2004	7	10.1111/j.1365-2222.2004.1886.x	Allergy; Immunology
Acid stress in the pathology of asthma. Although alteration of airway pH may serve an innate host defense capacity, it also is implicated in the pathophysiology of obstructive airway diseases. Acid-induced asthma appears in association with gastroesophageal reflux after accidental inhalation of acid (fog, pollution, and workplace exposure) and in the presence of altered airway pH homeostasis. Endogenous and exogenous exposures to acids evoke cough, bronchoconstriction, airway hyperreactivity, microvascular leakage, and heightened production of mucous, fluid, and nitric oxide. Abnormal acidity of the airways is reflected in exhaled breath assays. The intimate mechanisms of acid-induced airway obstruction are dependent on activation of capsaicin-sensitive sensory nerves. Protons activate these nerves with the subsequent release of tachykinins (major mediators of this pathway) that, in conjunction with kinins, nitric oxide, oxygen radicals, and proteases, modulate diverse aspects of airway dysfunction and inflammation. The recognition that acid stress might initiate or exacerbate airway obstructive symptomatology has prompted the consideration of new therapies targeting pH homeostasis.. airway ph| gastroesophageal reflux| tachykinins| capsaicin| exhaled breath condensate| acid| asthma| chronic obstructive pulmonary disease| cough| bronchoconstriction|exhaled breath condensate| induced airway hyperresponsiveness| tachykinin receptor antagonists| guinea-pigs| citric-acid| induced bronchoconstriction| nitric-oxide| gastroesophageal-reflux| cystic-fibrosis| induced cough.	APR-2004	airway ph| gastroesophageal reflux| tachykinins| capsaicin| exhaled breath condensate| acid| asthma| chronic obstructive pulmonary disease| cough| bronchoconstriction|exhaled breath condensate| induced airway hyperresponsiveness| tachykinin receptor antagonists| guinea-pigs| citric-acid| induced bronchoconstriction| nitric-oxide| gastroesophageal-reflux| cystic-fibrosis| induced cough	Ricciardolo, FLM; Gaston, B; Hunt, J	Acid stress in the pathology of asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	airway pH; gastroesophageal reflux; tachykinins; capsaicin; exhaled breath condensate; acid; asthma; chronic obstructive pulmonary disease; cough; bronchoconstriction	EXHALED BREATH CONDENSATE; INDUCED AIRWAY HYPERRESPONSIVENESS; TACHYKININ RECEPTOR ANTAGONISTS; GUINEA-PIGS; CITRIC-ACID; INDUCED BRONCHOCONSTRICTION; NITRIC-OXIDE; GASTROESOPHAGEAL-REFLUX; CYSTIC-FIBROSIS; INDUCED COUGH	Although alteration of airway pH may serve an innate host defense capacity, it also is implicated in the pathophysiology of obstructive airway diseases. Acid-induced asthma appears in association with gastroesophageal reflux after accidental inhalation of acid (fog, pollution, and workplace exposure) and in the presence of altered airway pH homeostasis. Endogenous and exogenous exposures to acids evoke cough, bronchoconstriction, airway hyperreactivity, microvascular leakage, and heightened production of mucous, fluid, and nitric oxide. Abnormal acidity of the airways is reflected in exhaled breath assays. The intimate mechanisms of acid-induced airway obstruction are dependent on activation of capsaicin-sensitive sensory nerves. Protons activate these nerves with the subsequent release of tachykinins (major mediators of this pathway) that, in conjunction with kinins, nitric oxide, oxygen radicals, and proteases, modulate diverse aspects of airway dysfunction and inflammation. The recognition that acid stress might initiate or exacerbate airway obstructive symptomatology has prompted the consideration of new therapies targeting pH homeostasis.	98	117	2004	10	10.1016/j.jaci.2003.12.034	Allergy; Immunology
Prospective study of air pollution and bronchitic symptoms in children with asthma. The relationship of bronchitic symptoms to ambient particulate matter and to particulate elemental and organic carbon (OC), nitrogen dioxide (NO2), and other gaseous pollutants was examined in a cohort of children with asthma in 12 Southern California communities. Symptoms, assessed yearly by questionnaire from 1996 to 1999, were associated with the yearly variability of particulate matter with aerodynamic diameter less than 2.5 mum (odds ratio [OR] 1.09/mug/m(3); 95% confidence interval [CI] 1.01-1.17), OC (OR 1.41/mug/m(3); 95% CI 1.12-1.78), NO2 (OR 1.07/ppb; 95% CI 1.02-1.13), and ozone (OR 1.06/ppb; 95% Cl 1.00-1.12). The ORs associated with yearly within-community variability in air pollution were larger than the effect of the between-community 4-year average concentrations. In two pollutant models, the effects of yearly variation in OC and NO2 were only modestly reduced by adjusting for other pollutants, except in a model containing both OC and NO2; the effects of all other pollutants were reduced after adjusting for OC or NO2. We conclude that OC and NO2 deserve greater attention as potential causes of the chronic symptoms of bronchitis in children with asthma and that previous cross-sectional studies may have underestimated the risks associated with air pollution.. asthma| epidemiology| air pollution| child| particulate matter|southern california children| diesel exhaust particles| lung-function growth| respiratory health| organic aerosol| inhalable particles| personal exposure| nitrogen-dioxide| association| admissions.	OCT 1-2003	asthma| epidemiology| air pollution| child| particulate matter|southern california children| diesel exhaust particles| lung-function growth| respiratory health| organic aerosol| inhalable particles| personal exposure| nitrogen-dioxide| association| admissions	McConnell, R; Berhane, K; Gilliland, F; Molitor, J; Thomas, D; Lurmann, F; Avol, E; Gauderman, WJ; Peters, JM	Prospective study of air pollution and bronchitic symptoms in children with asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; epidemiology; air pollution; child; particulate matter	SOUTHERN CALIFORNIA CHILDREN; DIESEL EXHAUST PARTICLES; LUNG-FUNCTION GROWTH; RESPIRATORY HEALTH; ORGANIC AEROSOL; INHALABLE PARTICLES; PERSONAL EXPOSURE; NITROGEN-DIOXIDE; ASSOCIATION; ADMISSIONS	The relationship of bronchitic symptoms to ambient particulate matter and to particulate elemental and organic carbon (OC), nitrogen dioxide (NO2), and other gaseous pollutants was examined in a cohort of children with asthma in 12 Southern California communities. Symptoms, assessed yearly by questionnaire from 1996 to 1999, were associated with the yearly variability of particulate matter with aerodynamic diameter less than 2.5 mum (odds ratio [OR] 1.09/mug/m(3); 95% confidence interval [CI] 1.01-1.17), OC (OR 1.41/mug/m(3); 95% CI 1.12-1.78), NO2 (OR 1.07/ppb; 95% CI 1.02-1.13), and ozone (OR 1.06/ppb; 95% Cl 1.00-1.12). The ORs associated with yearly within-community variability in air pollution were larger than the effect of the between-community 4-year average concentrations. In two pollutant models, the effects of yearly variation in OC and NO2 were only modestly reduced by adjusting for other pollutants, except in a model containing both OC and NO2; the effects of all other pollutants were reduced after adjusting for OC or NO2. We conclude that OC and NO2 deserve greater attention as potential causes of the chronic symptoms of bronchitis in children with asthma and that previous cross-sectional studies may have underestimated the risks associated with air pollution.	48	117	2003	8	10.1164/rccm.200304-466OC	General & Internal Medicine; Respiratory System
A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics. The inducible isoenzyme of nitric oxide synthase (iNOS) generates nitric oxide (NO) in inflammatory diseases such as asthma. The prodrug L-N-6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51) is rapidly converted in vivo to the active metabolite L-N-6-(1-iminoethyl)lysine (L-NIL). Initially, we performed in vitro experiments in human primary airway epithelial cells to demonstrate that L-NIL causes inhibition of iNOS. In a randomized double-blind placebo-controlled crossover trial, SC-51 was administered as a single oral dose (20 or 200 mg) in separate cohorts of healthy volunteers (two groups of n=12) and mild asthmatic patients (two groups of n=12). SC-51 (200 mg) reduced exhaled breath NO levels to <2 ppb in both healthy volunteers (P<0.001) and mild asthmatics (P<0.001) within 15 min, representing >90% inhibition of baseline levels of NO in asthmatic patients, with the effects lasting at least 72 h. There were no significant effects on blood pressure, pulse rate, or respiratory function (FEV1). This study demonstrates that an inhibitor of iNOS produces marked inhibition of exhaled breath NO in normal and asthmatic subjects without producing the side effects observed following the systemic administration of non-selective NOS inhibitors, and thus provides support for the potential use of iNOS inhibitors to treat a range of inflammatory clinical disorders.. respiratory| pharmacology| tolerability|obstructive pulmonary-disease| inos inhibitor| airways| lung| mice| air| bronchodilator| nitrotyrosine| peroxynitrite| inflammation.	MAY-2003	respiratory| pharmacology| tolerability|obstructive pulmonary-disease| inos inhibitor| airways| lung| mice| air| bronchodilator| nitrotyrosine| peroxynitrite| inflammation	Hansel, TT; Kharitonov, SA; Donnelly, LE; Erin, EM; Currie, MG; Moore, WM; Manning, PT; Recker, DP; Barnes, PJ	A selective inhibitor of inducible nitric oxide synthase inhibits exhaled breath nitric oxide in healthy volunteers and asthmatics		FASEB JOURNAL	respiratory; pharmacology; tolerability	OBSTRUCTIVE PULMONARY-DISEASE; INOS INHIBITOR; AIRWAYS; LUNG; MICE; AIR; BRONCHODILATOR; NITROTYROSINE; PEROXYNITRITE; INFLAMMATION	The inducible isoenzyme of nitric oxide synthase (iNOS) generates nitric oxide (NO) in inflammatory diseases such as asthma. The prodrug L-N-6-(1-iminoethyl)lysine 5-tetrazole amide (SC-51) is rapidly converted in vivo to the active metabolite L-N-6-(1-iminoethyl)lysine (L-NIL). Initially, we performed in vitro experiments in human primary airway epithelial cells to demonstrate that L-NIL causes inhibition of iNOS. In a randomized double-blind placebo-controlled crossover trial, SC-51 was administered as a single oral dose (20 or 200 mg) in separate cohorts of healthy volunteers (two groups of n=12) and mild asthmatic patients (two groups of n=12). SC-51 (200 mg) reduced exhaled breath NO levels to <2 ppb in both healthy volunteers (P<0.001) and mild asthmatics (P<0.001) within 15 min, representing >90% inhibition of baseline levels of NO in asthmatic patients, with the effects lasting at least 72 h. There were no significant effects on blood pressure, pulse rate, or respiratory function (FEV1). This study demonstrates that an inhibitor of iNOS produces marked inhibition of exhaled breath NO in normal and asthmatic subjects without producing the side effects observed following the systemic administration of non-selective NOS inhibitors, and thus provides support for the potential use of iNOS inhibitors to treat a range of inflammatory clinical disorders.	59	117	2003	20	10.1096/fj.02-0633fje	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology
Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes. Toll-like receptor 4 (TLR4) is the principal receptor for bacterial endotoxin recognition, and functional variants in the gene confer endotoxin-hyporesponsiveness in humans. Furthermore, there is evidence that endotoxin exposure during early life is protective against the development of atopy and asthma, although this relationship remains poorly understood. It is therefore possible that genetic variation in the TLR4 locus contributes to asthma susceptibility. In this study we characterize the genetic diversity in the TLR4 locus and test for association between the common genetic variants and asthma-related phenotypes. In a cohort of 90 ethnically diverse subjects, we resequenced the TLR4 locus and identified a total of 29 single nucleotide polymorphisms. We assessed five common polymorphisms for evidence of association with asthma in two large family-based cohorts: a heterogeneous North American cohort (589 families), and a more homogenous population from northeastern Quebec, Canada (167 families). Using the transmission-disequilibrum test, we found no evidence of association for any of the polymorphisms tested, including two functional variants. Furthermore, we found no evidence for association between the TLR4 variants and four quantitative intermediate asthma- and atopy-related phenotypes. Based on these results, we found no evidence that genetic variation in TLR4 contributes to asthma susceptibility.. asthma| genetics| polymorphism| toll-like receptor 4| genetic association|single-nucleotide polymorphisms| house-dust endotoxin| linkage disequilibrium| bacterial lipopolysaccharide| haplotype structure| unified approach| cd14 gene| population| tlr4| mutations.	DEC 1-2002	asthma| genetics| polymorphism| toll-like receptor 4| genetic association|single-nucleotide polymorphisms| house-dust endotoxin| linkage disequilibrium| bacterial lipopolysaccharide| haplotype structure| unified approach| cd14 gene| population| tlr4| mutations	Raby, BA; Klimecki, WT; Laprise, C; Renaud, Y; Faith, J; Lemire, M; Greenwood, C; Weiland, KM; Lange, C; Palmer, LJ; Lazarus, R; Vercelli, D; Kwiatkowski, DJ; Silverman, EK; Martinez, FD; Hudson, TJ; Weiss, ST	Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; genetics; polymorphism; toll-like receptor 4; genetic association	SINGLE-NUCLEOTIDE POLYMORPHISMS; HOUSE-DUST ENDOTOXIN; LINKAGE DISEQUILIBRIUM; BACTERIAL LIPOPOLYSACCHARIDE; HAPLOTYPE STRUCTURE; UNIFIED APPROACH; CD14 GENE; POPULATION; TLR4; MUTATIONS	Toll-like receptor 4 (TLR4) is the principal receptor for bacterial endotoxin recognition, and functional variants in the gene confer endotoxin-hyporesponsiveness in humans. Furthermore, there is evidence that endotoxin exposure during early life is protective against the development of atopy and asthma, although this relationship remains poorly understood. It is therefore possible that genetic variation in the TLR4 locus contributes to asthma susceptibility. In this study we characterize the genetic diversity in the TLR4 locus and test for association between the common genetic variants and asthma-related phenotypes. In a cohort of 90 ethnically diverse subjects, we resequenced the TLR4 locus and identified a total of 29 single nucleotide polymorphisms. We assessed five common polymorphisms for evidence of association with asthma in two large family-based cohorts: a heterogeneous North American cohort (589 families), and a more homogenous population from northeastern Quebec, Canada (167 families). Using the transmission-disequilibrum test, we found no evidence of association for any of the polymorphisms tested, including two functional variants. Furthermore, we found no evidence for association between the TLR4 variants and four quantitative intermediate asthma- and atopy-related phenotypes. Based on these results, we found no evidence that genetic variation in TLR4 contributes to asthma susceptibility.	54	117	2002	8	10.1164/rrcm.200207-634OC	General & Internal Medicine; Respiratory System
Home and allergic characteristics of children with asthma in seven US urban communities and design of an environmental intervention: The Inner-City Asthma Study. Most published environmental remediation interventions have been directed at single allergens and have employed demanding strategies; few have been performed in the homes of inner-city children disproportionately burdened by asthma. Our objective was a) to describe the allergen sensitivities, environmental tobacco smoke (ETS) exposure, and home environmental characteristics of a national sample of inner-city children with moderate to severe asthma and b) to develop and implement a multifaceted, home-based comprehensive intervention to reduce home allergens and ETS, tailored to the specific sensitization and exposure profiles of those children. Allergen skin testing and a home evaluation were performed to determine the presence of ETS and factors known to be associated with increased indoor allergen levels. Based on published remediation techniques, a home environmental intervention, organized into modules, each addressing one of five specific allergen groups or ETS, was designed. Of 994 allergic children from seven U.S. urban communities, 937 successfully completed baseline interviews and home allergen surveys and were enrolled. More than 50% of children had positive skin tests to three or more allergen groups. Cockroaches were reported in 58% of homes, wall-to-wall carpeting in the child's bedroom in 55%, a smoker in 48%, mice or rats in 40%, and furry pets in 28%. More than 60% of enrolled families received four or more modules, and between 94% and 98% of all modules were completed. We conclude that most inner-city children with moderate to severe asthma are sensitized to multiple indoor allergens and that environmental factors known to be associated with asthma severity are commonly present in their homes. The intervention developed for the Inner-City Asthma Study employs accepted methods to address an array of allergens and ETS exposure while ensuring that the intervention is tailored to the specific sensitization profiles and home characteristics of these children.. environmental intervention| home environmental characteristics| inner-city children| pediatric asthma|risk-factors| childhood asthma| passive smoking| vacuum-cleaners| dog allergen| exposure| sensitization| efficiency| morbidity| health.	SEP-2002	environmental intervention| home environmental characteristics| inner-city children| pediatric asthma|risk-factors| childhood asthma| passive smoking| vacuum-cleaners| dog allergen| exposure| sensitization| efficiency| morbidity| health	Crain, EF; Walter, M; O'Connor, GT; Mitchell, H; Gruchalla, RS; Kattan, M; Malindzak, GS; Enright, P; Evans, R; Morgan, W; Stout, JW	Home and allergic characteristics of children with asthma in seven US urban communities and design of an environmental intervention: The Inner-City Asthma Study		ENVIRONMENTAL HEALTH PERSPECTIVES	environmental intervention; home environmental characteristics; inner-city children; pediatric asthma	RISK-FACTORS; CHILDHOOD ASTHMA; PASSIVE SMOKING; VACUUM-CLEANERS; DOG ALLERGEN; EXPOSURE; SENSITIZATION; EFFICIENCY; MORBIDITY; HEALTH	Most published environmental remediation interventions have been directed at single allergens and have employed demanding strategies; few have been performed in the homes of inner-city children disproportionately burdened by asthma. Our objective was a) to describe the allergen sensitivities, environmental tobacco smoke (ETS) exposure, and home environmental characteristics of a national sample of inner-city children with moderate to severe asthma and b) to develop and implement a multifaceted, home-based comprehensive intervention to reduce home allergens and ETS, tailored to the specific sensitization and exposure profiles of those children. Allergen skin testing and a home evaluation were performed to determine the presence of ETS and factors known to be associated with increased indoor allergen levels. Based on published remediation techniques, a home environmental intervention, organized into modules, each addressing one of five specific allergen groups or ETS, was designed. Of 994 allergic children from seven U.S. urban communities, 937 successfully completed baseline interviews and home allergen surveys and were enrolled. More than 50% of children had positive skin tests to three or more allergen groups. Cockroaches were reported in 58% of homes, wall-to-wall carpeting in the child's bedroom in 55%, a smoker in 48%, mice or rats in 40%, and furry pets in 28%. More than 60% of enrolled families received four or more modules, and between 94% and 98% of all modules were completed. We conclude that most inner-city children with moderate to severe asthma are sensitized to multiple indoor allergens and that environmental factors known to be associated with asthma severity are commonly present in their homes. The intervention developed for the Inner-City Asthma Study employs accepted methods to address an array of allergens and ETS exposure while ensuring that the intervention is tailored to the specific sensitization profiles and home characteristics of these children.	39	117	2002	7		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
IL-33-activated dendritic cells are critical for allergic airway inflammation. IL-33, a new member of the IL-1 family cytokine, is involved in Th2-type responses in a wide range of diseases and signals through the ST2 receptor expressed on many immune cells. Since the effects of IL-33 on DCs remain controversial, we investigated the ability of IL-33 to modulate DC functions in vitro and in vivo. Here, we report that IL-33 activates myeloid DCs to produce IL-6, IL-1 beta, TNF, CCL17 and to express high levels of CD40, CD80 OX40L and CCR7. Importantly, IL-33-activated DCs prime naive lymphocytes to produce the Th2 cytokines IL-5 and IL-13, but not IL-4. In vivo, IL-33 exposure induces DC recruitment and activation in the lung. Using an OVA-induced allergic lung inflammation model, we demonstrate that the reduced airway inflammation in ST2-deficient mice correlates with the failure in DC activation and migration to the draining LN. Finally, we show that adoptive transfer of IL-33-activated DCs exacerbates lung inflammation in a DC-driven model of allergic airway inflammation. These data demonstrate for the first time that IL-33 activates DCs during antigen presentation and thereby drives a Th2-type response in allergic lung inflammation.. allergy| cytokines| dc| il-33| lung inflammation|il-1-like cytokine il-33| t-cells| human eosinophils| human basophils| st2 receptor| murine model| mast-cells| th2 cells| in-vivo| asthma.	JUN-2011	allergy| cytokines| dc| il-33| lung inflammation|il-1-like cytokine il-33| t-cells| human eosinophils| human basophils| st2 receptor| murine model| mast-cells| th2 cells| in-vivo| asthma	Besnard, AG; Togbe, D; Guillou, N; Erard, F; Quesniaux, V; Ryffel, B	IL-33-activated dendritic cells are critical for allergic airway inflammation		EUROPEAN JOURNAL OF IMMUNOLOGY	Allergy; Cytokines; DC; IL-33; Lung inflammation	IL-1-LIKE CYTOKINE IL-33; T-CELLS; HUMAN EOSINOPHILS; HUMAN BASOPHILS; ST2 RECEPTOR; MURINE MODEL; MAST-CELLS; TH2 CELLS; IN-VIVO; ASTHMA	IL-33, a new member of the IL-1 family cytokine, is involved in Th2-type responses in a wide range of diseases and signals through the ST2 receptor expressed on many immune cells. Since the effects of IL-33 on DCs remain controversial, we investigated the ability of IL-33 to modulate DC functions in vitro and in vivo. Here, we report that IL-33 activates myeloid DCs to produce IL-6, IL-1 beta, TNF, CCL17 and to express high levels of CD40, CD80 OX40L and CCR7. Importantly, IL-33-activated DCs prime naive lymphocytes to produce the Th2 cytokines IL-5 and IL-13, but not IL-4. In vivo, IL-33 exposure induces DC recruitment and activation in the lung. Using an OVA-induced allergic lung inflammation model, we demonstrate that the reduced airway inflammation in ST2-deficient mice correlates with the failure in DC activation and migration to the draining LN. Finally, we show that adoptive transfer of IL-33-activated DCs exacerbates lung inflammation in a DC-driven model of allergic airway inflammation. These data demonstrate for the first time that IL-33 activates DCs during antigen presentation and thereby drives a Th2-type response in allergic lung inflammation.	44	116	2011	12	10.1002/eji.201041033	Immunology
Clinical effects of sulphite additives. P>Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Topical, oral or parenteral exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however, exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. While contact sensitivity to sulphite additives in topical medications is increasingly being recognized, skin reactions also occur after ingestion of or parenteral exposure to sulphites. Most studies report a 3-10% prevalence of sulphite sensitivity among asthmatic subjects following ingestion of these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. In addition to episodic and acute symptoms, sulphites may also contribute to chronic skin and respiratory symptoms. To date, the mechanisms underlying sulphite sensitivity remain unclear, although a number of potential mechanisms have been proposed. Physicians should be aware of the range of clinical manifestations of sulphite sensitivity, as well as the potential sources of exposure. Minor modifications to diet or behaviour lead to excellent clinical outcomes for sulphite-sensitive individuals.. metabisulfite-induced bronchoconstriction| dioxide-induced bronchoconstriction| allergic contact-dermatitis| chronic childhood asthma| sodium metabisulfite| sulfur-dioxide| occupational asthma| bronchial hyperreactivity| bronchodilator solutions| inhaled metabisulfite.	NOV-2009	metabisulfite-induced bronchoconstriction| dioxide-induced bronchoconstriction| allergic contact-dermatitis| chronic childhood asthma| sodium metabisulfite| sulfur-dioxide| occupational asthma| bronchial hyperreactivity| bronchodilator solutions| inhaled metabisulfite	Vally, H; Misso, NLA; Madan, V	Clinical effects of sulphite additives		CLINICAL AND EXPERIMENTAL ALLERGY		METABISULFITE-INDUCED BRONCHOCONSTRICTION; DIOXIDE-INDUCED BRONCHOCONSTRICTION; ALLERGIC CONTACT-DERMATITIS; CHRONIC CHILDHOOD ASTHMA; SODIUM METABISULFITE; SULFUR-DIOXIDE; OCCUPATIONAL ASTHMA; BRONCHIAL HYPERREACTIVITY; BRONCHODILATOR SOLUTIONS; INHALED METABISULFITE	P>Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Topical, oral or parenteral exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however, exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. While contact sensitivity to sulphite additives in topical medications is increasingly being recognized, skin reactions also occur after ingestion of or parenteral exposure to sulphites. Most studies report a 3-10% prevalence of sulphite sensitivity among asthmatic subjects following ingestion of these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. In addition to episodic and acute symptoms, sulphites may also contribute to chronic skin and respiratory symptoms. To date, the mechanisms underlying sulphite sensitivity remain unclear, although a number of potential mechanisms have been proposed. Physicians should be aware of the range of clinical manifestations of sulphite sensitivity, as well as the potential sources of exposure. Minor modifications to diet or behaviour lead to excellent clinical outcomes for sulphite-sensitive individuals.	100	116	2009	9	10.1111/j.1365-2222.2009.03362.x	Allergy; Immunology
Mouse models of allergic asthma: acute and chronic allergen challenge. Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiological and immunological processes are not fully understood. Animal models have been used to elucidate asthma pathophysiology, and to identify and evaluate novel therapeutic targets. Several recent review articles (Epstein, 2004; Lloyd, 2007; Boyce and Austen, 2005; Zosky and Sly, 2007) have discussed the potential value of these models. Allergen challenge models reproduce many features of clinical asthma and have been widely used by investigators; however, the majority involve acute allergen challenge procedures. It is recognised that asthma is a chronic inflammatory disease resulting from continued or intermittent allergen exposure, usually via inhalation, and there has been a recent focus on developing chronic allergen exposure models, predominantly in mice. Here, we review the acute and chronic exposure mouse models, and consider their potential role and impact in the field of asthma research.. inhibits airway inflammation| severe persistent asthma| soluble il-4 receptor| murine model| bronchial hyperresponsiveness| pulmonary inflammation| monoclonal-antibody| atopic asthma| phosphodiesterase-4 inhibitor| cysteinyl-leukotrienes.	NOV-DEC-2008	inhibits airway inflammation| severe persistent asthma| soluble il-4 receptor| murine model| bronchial hyperresponsiveness| pulmonary inflammation| monoclonal-antibody| atopic asthma| phosphodiesterase-4 inhibitor| cysteinyl-leukotrienes	Nials, AT; Uddin, S	Mouse models of allergic asthma: acute and chronic allergen challenge		DISEASE MODELS & MECHANISMS		INHIBITS AIRWAY INFLAMMATION; SEVERE PERSISTENT ASTHMA; SOLUBLE IL-4 RECEPTOR; MURINE MODEL; BRONCHIAL HYPERRESPONSIVENESS; PULMONARY INFLAMMATION; MONOCLONAL-ANTIBODY; ATOPIC ASTHMA; PHOSPHODIESTERASE-4 INHIBITOR; CYSTEINYL-LEUKOTRIENES	Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiological and immunological processes are not fully understood. Animal models have been used to elucidate asthma pathophysiology, and to identify and evaluate novel therapeutic targets. Several recent review articles (Epstein, 2004; Lloyd, 2007; Boyce and Austen, 2005; Zosky and Sly, 2007) have discussed the potential value of these models. Allergen challenge models reproduce many features of clinical asthma and have been widely used by investigators; however, the majority involve acute allergen challenge procedures. It is recognised that asthma is a chronic inflammatory disease resulting from continued or intermittent allergen exposure, usually via inhalation, and there has been a recent focus on developing chronic allergen exposure models, predominantly in mice. Here, we review the acute and chronic exposure mouse models, and consider their potential role and impact in the field of asthma research.	85	116	2008	8	10.1242/dmm.000323	Cell Biology; Pathology
Asthma cases attributable to atopy: Results from the third national health and nutrition examination survey. Background: The percentage of asthma cases attributable to atopy is the subject of debate. Objectives: The objectives were to estimate the percentage of asthma cases in the US population attributable to atopy and to examine associations between allergen-specific skin tests and asthma. Methods: Data were obtained from the Third National Health and Nutrition Examination Survey, in which subjects age 6 to 59 years were skin tested with 10 allergens. Atopy was defined as at least 1 positive allergen-specific test. Doctor-diagnosed current asthma was assessed by questionnaire. Results: In the United States, 56.3% of the asthma cases were attributable to atopy, and that percentage was greater among males than females, among persons in the highest education category than in lower education categories, and among persons living in highly populated metropolitan areas than in all other areas. Each allergen-specific test was strongly associated with asthma before adjustment (odds ratios varied from 2.1 to 4.5); however, after adjustment by all the allergens, only tests to cat, Alternaria, white oak, and perennial rye were independently associated with asthma. Perennial rye was inversely associated with asthma. Of the 10 allergens, a positive response to cat accounted for the highest percentage of asthma cases (29.3%). Conclusion: About half of the current asthma cases in the US population represented by the Third National Health and Nutrition Examination Survey were attributable to atopy. Some allergen-specific skin tests were not independently associated with asthma. Clinical implications: If atopy could be prevented or reversed, or its effect on asthma blocked, then a large percentage of asthma cases in the US population could be prevented.. allergens| allergic sensitization| allergy skin test| asthma| atopy| epidemiology| nhanes iii| skin prick test| survey|house-dust mite| common allergens| cat allergen| association| sensitization| population| exposure| adolescents| reactivity| childhood.	NOV-2007	allergens| allergic sensitization| allergy skin test| asthma| atopy| epidemiology| nhanes iii| skin prick test| survey|house-dust mite| common allergens| cat allergen| association| sensitization| population| exposure| adolescents| reactivity| childhood	Arbes, SJ; Gergen, PJ; Vaughn, B; Zeldin, DC	Asthma cases attributable to atopy: Results from the third national health and nutrition examination survey		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergens; allergic sensitization; allergy skin test; asthma; atopy; epidemiology; NHANES III; skin prick test; survey	HOUSE-DUST MITE; COMMON ALLERGENS; CAT ALLERGEN; ASSOCIATION; SENSITIZATION; POPULATION; EXPOSURE; ADOLESCENTS; REACTIVITY; CHILDHOOD	Background: The percentage of asthma cases attributable to atopy is the subject of debate. Objectives: The objectives were to estimate the percentage of asthma cases in the US population attributable to atopy and to examine associations between allergen-specific skin tests and asthma. Methods: Data were obtained from the Third National Health and Nutrition Examination Survey, in which subjects age 6 to 59 years were skin tested with 10 allergens. Atopy was defined as at least 1 positive allergen-specific test. Doctor-diagnosed current asthma was assessed by questionnaire. Results: In the United States, 56.3% of the asthma cases were attributable to atopy, and that percentage was greater among males than females, among persons in the highest education category than in lower education categories, and among persons living in highly populated metropolitan areas than in all other areas. Each allergen-specific test was strongly associated with asthma before adjustment (odds ratios varied from 2.1 to 4.5); however, after adjustment by all the allergens, only tests to cat, Alternaria, white oak, and perennial rye were independently associated with asthma. Perennial rye was inversely associated with asthma. Of the 10 allergens, a positive response to cat accounted for the highest percentage of asthma cases (29.3%). Conclusion: About half of the current asthma cases in the US population represented by the Third National Health and Nutrition Examination Survey were attributable to atopy. Some allergen-specific skin tests were not independently associated with asthma. Clinical implications: If atopy could be prevented or reversed, or its effect on asthma blocked, then a large percentage of asthma cases in the US population could be prevented.	22	116	2007	7	10.1016/j.jaci.2007.07.056	Allergy; Immunology
Ginkgo biloba leave extract: Biological, medicinal, and toxicological effects. Ginkgo biloba leave extract is among the most widely sold herbal dietary supplements in the United States. Its purported biological effects include: scavenging free radical; lowering oxidative stress; reducing neural damages, reducing platelets aggregation; anti-inflammation; anti-tumor activities; and anti-aging. Clinically, it has been prescribed to treat CNS disorders such as Alzheimer's disease and cognitive deficits. It exerts allergy and changes in bleeding time. While its mutagenicity or carcinogenic activity has not been reported, its components, quercetin, kaempferol and rutin have been shown to be genotoxic. There are no standards or guidelines regulating the constituent components of Ginkgo biloba leave extract nor are exposure limits imposed. Safety evaluation of Ginkgo biloba leave extract is being conducted by the U.S. National Toxicology Program.. gingko biloba leave extract| biological and toxicological effects| ginkgolidc| quercetin|herb-drug interactions| induced neuronal death| global brain ischemia| egb 761 protects| dna-damage| induced nephrotoxicity| induced toxicity| nitric-oxide| in-vitro| cytochrome-p450 phenotypes.	2007	gingko biloba leave extract| biological and toxicological effects| ginkgolidc| quercetin|herb-drug interactions| induced neuronal death| global brain ischemia| egb 761 protects| dna-damage| induced nephrotoxicity| induced toxicity| nitric-oxide| in-vitro| cytochrome-p450 phenotypes	Chan, PC; Xia, QS; Fu, PP	Ginkgo biloba leave extract: Biological, medicinal, and toxicological effects		JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS	Gingko biloba leave extract; biological and toxicological effects; ginkgolidc; quercetin	HERB-DRUG INTERACTIONS; INDUCED NEURONAL DEATH; GLOBAL BRAIN ISCHEMIA; EGB 761 PROTECTS; DNA-DAMAGE; INDUCED NEPHROTOXICITY; INDUCED TOXICITY; NITRIC-OXIDE; IN-VITRO; CYTOCHROME-P450 PHENOTYPES	Ginkgo biloba leave extract is among the most widely sold herbal dietary supplements in the United States. Its purported biological effects include: scavenging free radical; lowering oxidative stress; reducing neural damages, reducing platelets aggregation; anti-inflammation; anti-tumor activities; and anti-aging. Clinically, it has been prescribed to treat CNS disorders such as Alzheimer's disease and cognitive deficits. It exerts allergy and changes in bleeding time. While its mutagenicity or carcinogenic activity has not been reported, its components, quercetin, kaempferol and rutin have been shown to be genotoxic. There are no standards or guidelines regulating the constituent components of Ginkgo biloba leave extract nor are exposure limits imposed. Safety evaluation of Ginkgo biloba leave extract is being conducted by the U.S. National Toxicology Program.	161	116	2007	34	10.1080/10590500701569414	Oncology; Environmental Sciences & Ecology; Toxicology
Personal and ambient air pollution is associated with increased exhaled nitric oxide in children with asthma. BACKGROUND: Research has shown associations between pediatric asthma outcomes and airborne particulate matter (PM). The importance of particle components remains to be determined. METHODS: We followed a panel of 45 schoolchildren with persistent asthma living in Southern California. Subjects were monitored over 10 days with offline fractional exhaled nitric oxide (FENO), a biomarker of airway inflammation. Personal active sampler exposures included continuous particulate matter < 2.5 mu m in aerodynamic diameter (PM2.5), 24-hr PM2.5 elemental and organic carbon (EC, OC), and 24-hr nitrogen dioxide. Ambient exposures included PM2.5, PM2.5 EC and OC, and NO2. Data were analyzed with mixed models controlling for personal temperature, humidity and 10-day period. RESULTS: The strongest positive associations were between FENO and 2-day average pollutant concentrations. Per interquartile range pollutant increase, these were: for 24 mu g/m(3) personal PM2.5, 1.1 ppb F-ENO [95% confidence interval (CI), 0.1-1.9]; for 0.6 mu g/m(3) personal EC, 0.7 ppb FENO (95% CI, 0.3-1.1); for 17 ppb personal NO2, 1.6 ppb FENO (95% CI, 0.4-2.8). Larger associations were found for ambient EC and smaller associations for ambient NO2. Ambient PM2.5 and personal and ambient OC were significant only in subjects taking inhaled corticosteroids (ICS) alone. Subjects taking both ICS and antileukotrienes showed no significant associations. Distributed lag models showed personal PM2.5 in the preceding 5 hr was associated with F-ENO. In two-pollutant models, the most robust associations were for personal and ambient EC and NO2, and for personal but not ambient PM2.5. CONCLUSION: PM associations with airway inflammation in asthmatics may be missed using ambient particle mass, which may not sufficiently represent causal pollutant components from fossil fuel combustion.. asthma| epidemiology| exhaled nitric oxide| longitudinal data analysis| nitrogen dioxide| ozone| panel study| particulate air pollution|antiinflammatory medication use| particulate-matter| nitrogen-dioxide| healthy-subjects| exposure| symptoms| flow| particles| montelukast| population.	NOV-2006	asthma| epidemiology| exhaled nitric oxide| longitudinal data analysis| nitrogen dioxide| ozone| panel study| particulate air pollution|antiinflammatory medication use| particulate-matter| nitrogen-dioxide| healthy-subjects| exposure| symptoms| flow| particles| montelukast| population	Delfino, RJ; Staimer, N; Gillen, D; Tjoa, T; Sioutas, C; Fung, K; George, SC; Kleinman, MT	Personal and ambient air pollution is associated with increased exhaled nitric oxide in children with asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; epidemiology; exhaled nitric oxide; longitudinal data analysis; nitrogen dioxide; ozone; panel study; particulate air pollution	ANTIINFLAMMATORY MEDICATION USE; PARTICULATE-MATTER; NITROGEN-DIOXIDE; HEALTHY-SUBJECTS; EXPOSURE; SYMPTOMS; FLOW; PARTICLES; MONTELUKAST; POPULATION	BACKGROUND: Research has shown associations between pediatric asthma outcomes and airborne particulate matter (PM). The importance of particle components remains to be determined. METHODS: We followed a panel of 45 schoolchildren with persistent asthma living in Southern California. Subjects were monitored over 10 days with offline fractional exhaled nitric oxide (FENO), a biomarker of airway inflammation. Personal active sampler exposures included continuous particulate matter < 2.5 mu m in aerodynamic diameter (PM2.5), 24-hr PM2.5 elemental and organic carbon (EC, OC), and 24-hr nitrogen dioxide. Ambient exposures included PM2.5, PM2.5 EC and OC, and NO2. Data were analyzed with mixed models controlling for personal temperature, humidity and 10-day period. RESULTS: The strongest positive associations were between FENO and 2-day average pollutant concentrations. Per interquartile range pollutant increase, these were: for 24 mu g/m(3) personal PM2.5, 1.1 ppb F-ENO [95% confidence interval (CI), 0.1-1.9]; for 0.6 mu g/m(3) personal EC, 0.7 ppb FENO (95% CI, 0.3-1.1); for 17 ppb personal NO2, 1.6 ppb FENO (95% CI, 0.4-2.8). Larger associations were found for ambient EC and smaller associations for ambient NO2. Ambient PM2.5 and personal and ambient OC were significant only in subjects taking inhaled corticosteroids (ICS) alone. Subjects taking both ICS and antileukotrienes showed no significant associations. Distributed lag models showed personal PM2.5 in the preceding 5 hr was associated with F-ENO. In two-pollutant models, the most robust associations were for personal and ambient EC and NO2, and for personal but not ambient PM2.5. CONCLUSION: PM associations with airway inflammation in asthmatics may be missed using ambient particle mass, which may not sufficiently represent causal pollutant components from fossil fuel combustion.	49	116	2006	8	10.1289/ehp.9141	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Does antibiotic exposure during infancy lead to development of asthma? A systematic review and metaanalysis. Objectives: To determine the association between antibiotic exposure in the first year of life and the development of childhood asthma. Design: Metaanalysis of observational studies retrieved through systematic search of all available electronic data sources. Studies included in the metaanalyses were those with populations exposed to one or more courses of antibiotics during the first year of life, and asthma diagnosis was defined as diagnosis by a physician between the age of 1 to 18 years. Setting: Retrospective and prospective studies published in the English-language literature from 1966 to present. Results: Eight studies (four prospective and four retrospective) examined the association between exposure to at least one course of antibiotics and development of childhood asthma. The total number of subjects for the analysis comparing exposure to at least one antibiotic to no exposure in the first year of life was 12,082 children and 1,817 asthma cases. In the dose-response analysis, we included data from a total of 27,167 children and 3,392 asthma cases. The pooled odds ratio (OR) for the eight studies was 2.05 (95% confidence interval [CI], 1.41 to 2.99). The association was significantly stronger in the retrospective studies (OR, 2.82; 95% CI, 2.07 to 3.85) than the prospective studies (OR, 1.12; 95% CI, 0.88 to 1.42). Five of the eight studies examined whether the association was related to the number of courses of antibiotics taken in the first year of life. The overall OR for the dose-response analysis was 1.16 (95% CI, 1.05 to 1.28) for each additional course of antibiotics; however, this association was not significantly stronger in the retrospective studies (OR, 1.37; 95% CI, 1.18 to 1.60) relative to the prospective studies (OR, 1.07; 95% CI, 0.95 to 1.20). Conclusions: Exposure to at least one course of antibiotics in the first year of life appears to be a risk factor for the development of childhood asthma. Because of the limitations of the studies conducted to date, additional large-scale, prospective studies are needed to confirm this potential association.. antibiotics| childhood asthma| pediatrics|early-childhood| allergic disease| birth cohort| infectious-diseases| 1st year| risk| prevalence| life| rhinitis| database.	MAR-2006	antibiotics| childhood asthma| pediatrics|early-childhood| allergic disease| birth cohort| infectious-diseases| 1st year| risk| prevalence| life| rhinitis| database	Marra, F; Lynd, L; Coombes, M; Richardson, K; Legal, M; FitzGerald, JM; Marra, CA	Does antibiotic exposure during infancy lead to development of asthma? A systematic review and metaanalysis		CHEST	antibiotics; childhood asthma; pediatrics	EARLY-CHILDHOOD; ALLERGIC DISEASE; BIRTH COHORT; INFECTIOUS-DISEASES; 1ST YEAR; RISK; PREVALENCE; LIFE; RHINITIS; DATABASE	Objectives: To determine the association between antibiotic exposure in the first year of life and the development of childhood asthma. Design: Metaanalysis of observational studies retrieved through systematic search of all available electronic data sources. Studies included in the metaanalyses were those with populations exposed to one or more courses of antibiotics during the first year of life, and asthma diagnosis was defined as diagnosis by a physician between the age of 1 to 18 years. Setting: Retrospective and prospective studies published in the English-language literature from 1966 to present. Results: Eight studies (four prospective and four retrospective) examined the association between exposure to at least one course of antibiotics and development of childhood asthma. The total number of subjects for the analysis comparing exposure to at least one antibiotic to no exposure in the first year of life was 12,082 children and 1,817 asthma cases. In the dose-response analysis, we included data from a total of 27,167 children and 3,392 asthma cases. The pooled odds ratio (OR) for the eight studies was 2.05 (95% confidence interval [CI], 1.41 to 2.99). The association was significantly stronger in the retrospective studies (OR, 2.82; 95% CI, 2.07 to 3.85) than the prospective studies (OR, 1.12; 95% CI, 0.88 to 1.42). Five of the eight studies examined whether the association was related to the number of courses of antibiotics taken in the first year of life. The overall OR for the dose-response analysis was 1.16 (95% CI, 1.05 to 1.28) for each additional course of antibiotics; however, this association was not significantly stronger in the retrospective studies (OR, 1.37; 95% CI, 1.18 to 1.60) relative to the prospective studies (OR, 1.07; 95% CI, 0.95 to 1.20). Conclusions: Exposure to at least one course of antibiotics in the first year of life appears to be a risk factor for the development of childhood asthma. Because of the limitations of the studies conducted to date, additional large-scale, prospective studies are needed to confirm this potential association.	29	116	2006	9	10.1378/chest.129.3.610	General & Internal Medicine; Respiratory System
Adverse health effects from ambient air pollution in relation to residential wood combustion in modern society. This is a review of the adverse health effects of ambient air pollution in relation to residential wood combustion in modem society. From a literature search of PubMed, nine relevant studies were identified. All of them focused on the effects of short-term exposure such as asthma, respiratory symptoms, daily mortality, and lung function. Substantial quantitative information was only found for acute asthma in relation to particulate matter with an aerodynamic diameter of <10 mum. In comparison with the present general estimations for ambient particulate matter and adverse health effects, the relative risks were even stronger in the studies in which residential wood combustion was considered a major source of particulate matter. Thus there seems to be no reason to assume that the effects of particulate matter in areas polluted by wood smoke are weaker than elsewhere.. air pollution| asthma| biomass combustion| epidemiology| particulate matter| review| short-term exposure| wood smoke|fine particulate matter| emergency room visits| santa-clara county| source apportionment| organic-compounds| daily mortality| asthma| children| particles| seattle.	AUG-2003	air pollution| asthma| biomass combustion| epidemiology| particulate matter| review| short-term exposure| wood smoke|fine particulate matter| emergency room visits| santa-clara county| source apportionment| organic-compounds| daily mortality| asthma| children| particles| seattle	Boman, BC; Forsberg, AB; Jarvholm, BG	Adverse health effects from ambient air pollution in relation to residential wood combustion in modern society		SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH	air pollution; asthma; biomass combustion; epidemiology; particulate matter; review; short-term exposure; wood smoke	FINE PARTICULATE MATTER; EMERGENCY ROOM VISITS; SANTA-CLARA COUNTY; SOURCE APPORTIONMENT; ORGANIC-COMPOUNDS; DAILY MORTALITY; ASTHMA; CHILDREN; PARTICLES; SEATTLE	This is a review of the adverse health effects of ambient air pollution in relation to residential wood combustion in modem society. From a literature search of PubMed, nine relevant studies were identified. All of them focused on the effects of short-term exposure such as asthma, respiratory symptoms, daily mortality, and lung function. Substantial quantitative information was only found for acute asthma in relation to particulate matter with an aerodynamic diameter of <10 mum. In comparison with the present general estimations for ambient particulate matter and adverse health effects, the relative risks were even stronger in the studies in which residential wood combustion was considered a major source of particulate matter. Thus there seems to be no reason to assume that the effects of particulate matter in areas polluted by wood smoke are weaker than elsewhere.	60	116	2003	10		Public, Environmental & Occupational Health
Dustborne and airborne fungal propagules represent a different spectrum of fungi with differing relations to home characteristics. Background: Exposure to fungi is often assessed by culturing floor dust or air samples. Our objective was to evaluate the relationships between dustborne and airborne fungi and to identify factors that modify these relationships. Methods: From November 1994 to September 1996 sequential duplicate 45-l air samples were collected in bedrooms of 496 homes in the Boston area, using a Burkard culture plate sampler. After air sampling, bedroom floors were sampled with a vacuum cleaner that was modified to collect dust in a cellulose extraction thimble. Dust was sieved, and the fine dust was dilution-plated onto DG-18 media. Results: Concentrations of total culturable fungi per gram of bedroom-floor dust were correlated weakly, but significantly, with those of indoor air (r = 0.13, P < 0.05). Concentrations of some individual taxa in the dust and indoor air were also weakly associated. Adjusting for the concentrations of fungi in outdoor air, dustborne fungal concentrations were positively associated with those in indoor air for the taxa Cladosporium and Penicillium , but not for total fungi. The indoor air fungal levels were often predicted by different covariates to those predicting fungal levels in dust. The type of housing (house or apartment) and the presence of carpeting were often predictive factors for dust fungi. In contrast, outdoor fungal levels were often predictive of the indoor air fungal levels. Conclusions: Because our data do not indicate a strong overall relationship between culturable fungi in dust and indoor air, the results from these two methods (dust and air sampling) likely represent different types of potential fungal exposures to residents. It may be essential to collect both air and dust samples, as well as information on housing characteristics, as indicators for fungal exposure.. air sampling| dust sampling| fungi| home characteristics| mold|in-house dust| residential characteristics| respiratory symptoms| indoor environment| domestic interiors| exposure| health| children| asthma| prevalence.	JAN-2003	air sampling| dust sampling| fungi| home characteristics| mold|in-house dust| residential characteristics| respiratory symptoms| indoor environment| domestic interiors| exposure| health| children| asthma| prevalence	Chew, GL; Rogers, C; Burge, HA; Muilenberg, ML; Gold, DR	Dustborne and airborne fungal propagules represent a different spectrum of fungi with differing relations to home characteristics		ALLERGY	air sampling; dust sampling; fungi; home characteristics; mold	IN-HOUSE DUST; RESIDENTIAL CHARACTERISTICS; RESPIRATORY SYMPTOMS; INDOOR ENVIRONMENT; DOMESTIC INTERIORS; EXPOSURE; HEALTH; CHILDREN; ASTHMA; PREVALENCE	Background: Exposure to fungi is often assessed by culturing floor dust or air samples. Our objective was to evaluate the relationships between dustborne and airborne fungi and to identify factors that modify these relationships. Methods: From November 1994 to September 1996 sequential duplicate 45-l air samples were collected in bedrooms of 496 homes in the Boston area, using a Burkard culture plate sampler. After air sampling, bedroom floors were sampled with a vacuum cleaner that was modified to collect dust in a cellulose extraction thimble. Dust was sieved, and the fine dust was dilution-plated onto DG-18 media. Results: Concentrations of total culturable fungi per gram of bedroom-floor dust were correlated weakly, but significantly, with those of indoor air (r = 0.13, P < 0.05). Concentrations of some individual taxa in the dust and indoor air were also weakly associated. Adjusting for the concentrations of fungi in outdoor air, dustborne fungal concentrations were positively associated with those in indoor air for the taxa Cladosporium and Penicillium , but not for total fungi. The indoor air fungal levels were often predicted by different covariates to those predicting fungal levels in dust. The type of housing (house or apartment) and the presence of carpeting were often predictive factors for dust fungi. In contrast, outdoor fungal levels were often predictive of the indoor air fungal levels. Conclusions: Because our data do not indicate a strong overall relationship between culturable fungi in dust and indoor air, the results from these two methods (dust and air sampling) likely represent different types of potential fungal exposures to residents. It may be essential to collect both air and dust samples, as well as information on housing characteristics, as indicators for fungal exposure.	42	116	2003	8	10.1034/j.1398-9995.2003.00013.x	Allergy; Immunology
Involvement of microbial components and toll-like receptors 2 and 4 in cytokine responses to air pollution particles. Inhalation of particulate matter (PM) may result in exacerbation of inflammatory airways disease, including asthma. Results from this laboratory have shown that the coarse inhalable particle fraction (PM2.5-10) is responsible for most of the PM effects on human airway macrophages (AM), including induction of cytokine production. Endotoxins associated with these particles account for a large part of their potency, as activity of PM can be inhibited by polymixin B and an activating moiety bound by lipopolysaccharide (LPS)-binding protein (LBP). The hypothesis behind the present study was that not only particle-bound LPS, but also Gram-negative (Gram-) and Gram-positive (Gram+) bacteria are responsible for PM-induced stimulation of AM, and therefore that PM are likely to activate receptors involved in recognition of microbes. Low level contamination of model pollution particles with environmental Staphyloccocus, Streptococcus, and Pseudomonas species was found to confer cytokine-inducing activity on inactive particles. Only one Gram- bacterium was sufficient for significant stimulatation of 100 AM, whereas at least three times more Gram+ bacteria were required for a similar level of response. Cytokine responses induced by PM as well as Gram+ and Gram- bacteria were inhibited by anti-CD14 antibody and required the presence of LBP-containing serum. The involvement of Toll-like receptor (TLR) 2 and 4 in recognition of PMZ.,o was investigated in transfected Chinese hamster ovary cells expressing CD14 and TLR2 or TLR4. TLR4 was found to be involved in PM2.5-10 and Pseudomonas-induced activation, whereas TLR2 activation was induced by both Gram+ and Gram- bacteria and by PM. The synthetic lipid A analog E5531 fully inhibited the response to purified LPS and partially inhibited the response to PM and Pseudomonas. In contrast, E5531 had no effect on the response to Staphylococcus. Taken together, these results implicate microbial components as important players in AM-dependent inflammatory responses to PM.. alveolar macrophage responses| emergency room visits| tnf-alpha| respiratory illnesses| insoluble components| signal-transduction| cutting edge| in-vitro| lipopolysaccharide| endotoxin.	NOV-2002	alveolar macrophage responses| emergency room visits| tnf-alpha| respiratory illnesses| insoluble components| signal-transduction| cutting edge| in-vitro| lipopolysaccharide| endotoxin	Becker, S; Fenton, MJ; Soukup, JM	Involvement of microbial components and toll-like receptors 2 and 4 in cytokine responses to air pollution particles		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		ALVEOLAR MACROPHAGE RESPONSES; EMERGENCY ROOM VISITS; TNF-ALPHA; RESPIRATORY ILLNESSES; INSOLUBLE COMPONENTS; SIGNAL-TRANSDUCTION; CUTTING EDGE; IN-VITRO; LIPOPOLYSACCHARIDE; ENDOTOXIN	Inhalation of particulate matter (PM) may result in exacerbation of inflammatory airways disease, including asthma. Results from this laboratory have shown that the coarse inhalable particle fraction (PM2.5-10) is responsible for most of the PM effects on human airway macrophages (AM), including induction of cytokine production. Endotoxins associated with these particles account for a large part of their potency, as activity of PM can be inhibited by polymixin B and an activating moiety bound by lipopolysaccharide (LPS)-binding protein (LBP). The hypothesis behind the present study was that not only particle-bound LPS, but also Gram-negative (Gram-) and Gram-positive (Gram+) bacteria are responsible for PM-induced stimulation of AM, and therefore that PM are likely to activate receptors involved in recognition of microbes. Low level contamination of model pollution particles with environmental Staphyloccocus, Streptococcus, and Pseudomonas species was found to confer cytokine-inducing activity on inactive particles. Only one Gram- bacterium was sufficient for significant stimulatation of 100 AM, whereas at least three times more Gram+ bacteria were required for a similar level of response. Cytokine responses induced by PM as well as Gram+ and Gram- bacteria were inhibited by anti-CD14 antibody and required the presence of LBP-containing serum. The involvement of Toll-like receptor (TLR) 2 and 4 in recognition of PMZ.,o was investigated in transfected Chinese hamster ovary cells expressing CD14 and TLR2 or TLR4. TLR4 was found to be involved in PM2.5-10 and Pseudomonas-induced activation, whereas TLR2 activation was induced by both Gram+ and Gram- bacteria and by PM. The synthetic lipid A analog E5531 fully inhibited the response to purified LPS and partially inhibited the response to PM and Pseudomonas. In contrast, E5531 had no effect on the response to Staphylococcus. Taken together, these results implicate microbial components as important players in AM-dependent inflammatory responses to PM.	41	116	2002	8	10.1165/rcmb.4868	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Childhood asthma hospitalization and residential exposure to state route traffic. This study investigated whether pediatric hospitalization for asthma was related to living near a road with heavy traffic. In this case-control study, cases (N=417) consisted of white children aged 0-14 years who were admitted for asthma and who resided in Erie County, New York, excluding the city of Buffalo. Controls (N=461) were children in the same age range admitted during the same time period for nonrespiratory diseases. Subjects' residential addresses were linked to traffic information provided by the New York State Department of Transportation. After adjustments for age and poverty level were made, children hospitalized for asthma were more likely to live on roads with the highest tertile of vehicle miles traveled (VMT) (odds ratio (OR): 1.93, 95% confidence interval (CI): 1.13-3.29) within 200 m and were more likely to have trucks and trailers passing by within 200m of their residence (OR=1.43, 95% CI: 1.03-1.99) compared to controls. However, childhood asthma hospitalization was not significantly associated with residential distance from state roads, annual VMT within 500m, or whether trucks or trailers passed by within 500m. This study suggests that exposure to high volumes of traffic/trucks within 200m of homes contributes to childhood asthma hospitalizations. (C) 2002 Elsevier Science (USA).. asthma hospitalization| childhood asthma| traffic| automobile exhaust|respiratory health| air-pollution| adjuvant activity| children| exhaust| admissions| particles| adults| roads| mice.	FEB-2002	asthma hospitalization| childhood asthma| traffic| automobile exhaust|respiratory health| air-pollution| adjuvant activity| children| exhaust| admissions| particles| adults| roads| mice	Lin, S; Munsie, JP; Hwang, SA; Fitzgerald, E; Cayo, MR	Childhood asthma hospitalization and residential exposure to state route traffic		ENVIRONMENTAL RESEARCH	asthma hospitalization; childhood asthma; traffic; automobile exhaust	RESPIRATORY HEALTH; AIR-POLLUTION; ADJUVANT ACTIVITY; CHILDREN; EXHAUST; ADMISSIONS; PARTICLES; ADULTS; ROADS; MICE	This study investigated whether pediatric hospitalization for asthma was related to living near a road with heavy traffic. In this case-control study, cases (N=417) consisted of white children aged 0-14 years who were admitted for asthma and who resided in Erie County, New York, excluding the city of Buffalo. Controls (N=461) were children in the same age range admitted during the same time period for nonrespiratory diseases. Subjects' residential addresses were linked to traffic information provided by the New York State Department of Transportation. After adjustments for age and poverty level were made, children hospitalized for asthma were more likely to live on roads with the highest tertile of vehicle miles traveled (VMT) (odds ratio (OR): 1.93, 95% confidence interval (CI): 1.13-3.29) within 200 m and were more likely to have trucks and trailers passing by within 200m of their residence (OR=1.43, 95% CI: 1.03-1.99) compared to controls. However, childhood asthma hospitalization was not significantly associated with residential distance from state roads, annual VMT within 500m, or whether trucks or trailers passed by within 500m. This study suggests that exposure to high volumes of traffic/trucks within 200m of homes contributes to childhood asthma hospitalizations. (C) 2002 Elsevier Science (USA).	30	116	2002	9	10.1006/enrs.2001.4303	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Respiratory health effects of air pollution: Update on biomass smoke and traffic pollution. Mounting evidence suggests that air pollution contributes to the large global burden of respiratory and allergic diseases, including asthma, chronic obstructive pulmonary disease, pneumonia, and possibly tuberculosis. Although associations between air pollution and respiratory disease are complex, recent epidemiologic studies have led to an increased recognition of the emerging importance of traffic-related air pollution in both developed and less-developed countries, as well as the continued importance of emissions from domestic fires burning biomass fuels, primarily in the less-developed world. Emissions from these sources lead to personal exposures to complex mixtures of air pollutants that change rapidly in space and time because of varying emission rates, distances from source, ventilation rates, and other factors. Although the high degree of variability in personal exposure to pollutants from these sources remains a challenge, newer methods for measuring and modeling these exposures are beginning to unravel complex associations with asthma and other respiratory tract diseases. These studies indicate that air pollution from these sources is a major preventable cause of increased incidence and exacerbation of respiratory disease. Physicians can help to reduce the risk of adverse respiratory effects of exposure to biomass and traffic air pollutants by promoting awareness and supporting individual and community-level interventions. (J Allergy Clin Immunol 2012; 129: 3-11.). biomass| traffic| chronic obstructive pulmonary disease| asthma| air pollutants| particulate matter|obstructive pulmonary-disease| diesel exhaust particles| environmental risk-factors| long-term exposure| ambient air| los-angeles| solid-fuel| streptococcus-pneumoniae| developing-countries| ultrafine particles.	JAN-2012	biomass| traffic| chronic obstructive pulmonary disease| asthma| air pollutants| particulate matter|obstructive pulmonary-disease| diesel exhaust particles| environmental risk-factors| long-term exposure| ambient air| los-angeles| solid-fuel| streptococcus-pneumoniae| developing-countries| ultrafine particles	Laumbach, RJ; Kipen, HM	Respiratory health effects of air pollution: Update on biomass smoke and traffic pollution		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Biomass; traffic; chronic obstructive pulmonary disease; asthma; air pollutants; particulate matter	OBSTRUCTIVE PULMONARY-DISEASE; DIESEL EXHAUST PARTICLES; ENVIRONMENTAL RISK-FACTORS; LONG-TERM EXPOSURE; AMBIENT AIR; LOS-ANGELES; SOLID-FUEL; STREPTOCOCCUS-PNEUMONIAE; DEVELOPING-COUNTRIES; ULTRAFINE PARTICLES	Mounting evidence suggests that air pollution contributes to the large global burden of respiratory and allergic diseases, including asthma, chronic obstructive pulmonary disease, pneumonia, and possibly tuberculosis. Although associations between air pollution and respiratory disease are complex, recent epidemiologic studies have led to an increased recognition of the emerging importance of traffic-related air pollution in both developed and less-developed countries, as well as the continued importance of emissions from domestic fires burning biomass fuels, primarily in the less-developed world. Emissions from these sources lead to personal exposures to complex mixtures of air pollutants that change rapidly in space and time because of varying emission rates, distances from source, ventilation rates, and other factors. Although the high degree of variability in personal exposure to pollutants from these sources remains a challenge, newer methods for measuring and modeling these exposures are beginning to unravel complex associations with asthma and other respiratory tract diseases. These studies indicate that air pollution from these sources is a major preventable cause of increased incidence and exacerbation of respiratory disease. Physicians can help to reduce the risk of adverse respiratory effects of exposure to biomass and traffic air pollutants by promoting awareness and supporting individual and community-level interventions. (J Allergy Clin Immunol 2012; 129: 3-11.)	92	115	2012	11	10.1016/j.jaci.2011.11.021	Allergy; Immunology
Counterregulation between the Fc epsilon RI Pathway and Antiviral Responses in Human Plasmacytoid Dendritic Cells. Plasmacytoid dendritic cells (pDCs) play essential roles in directing immune responses. These cells may be particularly important in determining the nature of immune responses to viral infections in patients with allergic asthma as well those with other atopic diseases. The purposes of this study were 1) to compare the functional capacity of pDCs in patients with one type of allergic disorder, allergic asthma, and controls; 2) to determine whether IgE cross-linking affects antiviral responses of influenza-exposed pDCs; and 3) to determine whether evidence of counterregulation of Fc epsilon RIa and IFN-alpha pathways exists in these cells. pDC function was assessed in a subset of asthma patients and in controls by measuring IFN-alpha production after exposure of purified pDCs to influenza viruses. Fc epsilon RIa expression on pDCs was determined by flow cytometry in blood samples from patients with allergic asthma and controls. pDCs from patients with asthma secreted significantly less IFN-alpha upon exposure to influenza A (572 versus 2815; p = 0.03), and secretion was inversely correlated with serum IgE levels. Moreover, IgE cross-linking prior to viral challenge resulted in 1) abrogation of the influenza-induced pDC IFN-alpha response; 2) diminished influenza and gardiquimod-induced TLR-7 upregulation in pDCs; and 3) interruption of influenza-induced upregulation of pDC maturation/ costimulatory molecules. In addition, exposure to influenza and gardiquimod resulted in upregulation of TLR-7, with concomitant downregulation of Fc epsilon RIa expression in pDCs. These data suggest that counterregulation of Fc epsilon RI and TLR-7 pathways exists in pDCs, and that IgE cross-linking impairs pDC antiviral responses. The Journal of Immunology, 2010, 184: 5999-6006.. interferon-producing cells| antigen-presenting cells| toll-like receptor-9| atopic-dermatitis| asthma| virus| expression| immunity| alpha| ige.	JUN 1-2010	interferon-producing cells| antigen-presenting cells| toll-like receptor-9| atopic-dermatitis| asthma| virus| expression| immunity| alpha| ige	Gill, MA; Bajwa, G; George, TA; Dong, CC; Dougherty, II; Jiang, N; Gan, VN; Gruchalla, RS	Counterregulation between the Fc epsilon RI Pathway and Antiviral Responses in Human Plasmacytoid Dendritic Cells		JOURNAL OF IMMUNOLOGY		INTERFERON-PRODUCING CELLS; ANTIGEN-PRESENTING CELLS; TOLL-LIKE RECEPTOR-9; ATOPIC-DERMATITIS; ASTHMA; VIRUS; EXPRESSION; IMMUNITY; ALPHA; IGE	Plasmacytoid dendritic cells (pDCs) play essential roles in directing immune responses. These cells may be particularly important in determining the nature of immune responses to viral infections in patients with allergic asthma as well those with other atopic diseases. The purposes of this study were 1) to compare the functional capacity of pDCs in patients with one type of allergic disorder, allergic asthma, and controls; 2) to determine whether IgE cross-linking affects antiviral responses of influenza-exposed pDCs; and 3) to determine whether evidence of counterregulation of Fc epsilon RIa and IFN-alpha pathways exists in these cells. pDC function was assessed in a subset of asthma patients and in controls by measuring IFN-alpha production after exposure of purified pDCs to influenza viruses. Fc epsilon RIa expression on pDCs was determined by flow cytometry in blood samples from patients with allergic asthma and controls. pDCs from patients with asthma secreted significantly less IFN-alpha upon exposure to influenza A (572 versus 2815; p = 0.03), and secretion was inversely correlated with serum IgE levels. Moreover, IgE cross-linking prior to viral challenge resulted in 1) abrogation of the influenza-induced pDC IFN-alpha response; 2) diminished influenza and gardiquimod-induced TLR-7 upregulation in pDCs; and 3) interruption of influenza-induced upregulation of pDC maturation/ costimulatory molecules. In addition, exposure to influenza and gardiquimod resulted in upregulation of TLR-7, with concomitant downregulation of Fc epsilon RIa expression in pDCs. These data suggest that counterregulation of Fc epsilon RI and TLR-7 pathways exists in pDCs, and that IgE cross-linking impairs pDC antiviral responses. The Journal of Immunology, 2010, 184: 5999-6006.	32	115	2010	8	10.4049/jimmunol.0901194	Immunology
Caesarean section delivery and the risk of allergic disorders in childhood. Background The composition of the intestinal flora in young children, if unfavourable, may increase the susceptibility to allergic disorders. Beneficial intestinal microbes originate from the maternal vaginal tract and thus are more likely to be transferred during vaginal births than during Caesarean sections (C-sections). Objective To determine whether children born by C-section have a different risk of allergic disorders compared with those delivered vaginally. We also tested the hypothesis that the risk of allergic disorders is highest for children born after 'repeat C-sections'. Methods A retrospective cohort study of 8953 children aged 3-10 years. Children diagnosed with allergic rhinoconjunctivitis (AR), asthma, atopic dermatitis (AD), or food allergies were identified from the Kaiser Permanente Northwest Region electronic records. The children's sex, birth weight, birth order, postnatal exposure to antibiotics as well as the mothers' age, ethnicity, education, marital status, smoking status during pregnancy, and use of asthma or hayfever medications were identified through the mothers' medical records or through the Oregon Birth Registry. Results The risk of being diagnosed with AR was significantly higher in the children born by C-section than in those delivered vaginally: adjusted odds ratio (OR)=1.37%, 95% confidence interval (CI)=1.14-1.63. Delivery by C-section was also associated with the subsequent diagnosis of asthma (OR=1.24%, 95% CI=1.01-1.53); this association was gender specific, with a positive association restricted to girls (OR for asthma in girls: OR=1.53%, 95% CI=1.11-2.10; in boys: OR=1.08%, 95% CI=0.81-1.43). There was no significant association between mode of delivery and AD. If children born in a 'repeat C-section' were considered separately the risk of being diagnosed with AR increased further (OR=1.78%, 95% CI=1.34-2.37). The same increase was noted for asthma in girls (OR=1.83%, 95% CI=1.13-2.97) but not in boys. Conclusion Caesarean sections may be associated with an increased risk of developing AR in childhood.. allergic rhinoconjunctivitis| asthma| atopic dermatitis| atopy| allergy| caesarean section| intestinal flora| intestinal microbes| risk of allergic disorders|placebo-controlled trial| hay-fever| atopic disease| bacterial-flora| asthma| children| mode| life| interleukin-10| complications.	NOV-2005	allergic rhinoconjunctivitis| asthma| atopic dermatitis| atopy| allergy| caesarean section| intestinal flora| intestinal microbes| risk of allergic disorders|placebo-controlled trial| hay-fever| atopic disease| bacterial-flora| asthma| children| mode| life| interleukin-10| complications	Renz-Polster, H; David, MR; Buist, AS; Vollmer, WM; O'Connor, EA; Frazier, EA; Wall, MA	Caesarean section delivery and the risk of allergic disorders in childhood		CLINICAL AND EXPERIMENTAL ALLERGY	allergic rhinoconjunctivitis; asthma; atopic dermatitis; atopy; allergy; Caesarean section; intestinal flora; intestinal microbes; risk of allergic disorders	PLACEBO-CONTROLLED TRIAL; HAY-FEVER; ATOPIC DISEASE; BACTERIAL-FLORA; ASTHMA; CHILDREN; MODE; LIFE; INTERLEUKIN-10; COMPLICATIONS	Background The composition of the intestinal flora in young children, if unfavourable, may increase the susceptibility to allergic disorders. Beneficial intestinal microbes originate from the maternal vaginal tract and thus are more likely to be transferred during vaginal births than during Caesarean sections (C-sections). Objective To determine whether children born by C-section have a different risk of allergic disorders compared with those delivered vaginally. We also tested the hypothesis that the risk of allergic disorders is highest for children born after 'repeat C-sections'. Methods A retrospective cohort study of 8953 children aged 3-10 years. Children diagnosed with allergic rhinoconjunctivitis (AR), asthma, atopic dermatitis (AD), or food allergies were identified from the Kaiser Permanente Northwest Region electronic records. The children's sex, birth weight, birth order, postnatal exposure to antibiotics as well as the mothers' age, ethnicity, education, marital status, smoking status during pregnancy, and use of asthma or hayfever medications were identified through the mothers' medical records or through the Oregon Birth Registry. Results The risk of being diagnosed with AR was significantly higher in the children born by C-section than in those delivered vaginally: adjusted odds ratio (OR)=1.37%, 95% confidence interval (CI)=1.14-1.63. Delivery by C-section was also associated with the subsequent diagnosis of asthma (OR=1.24%, 95% CI=1.01-1.53); this association was gender specific, with a positive association restricted to girls (OR for asthma in girls: OR=1.53%, 95% CI=1.11-2.10; in boys: OR=1.08%, 95% CI=0.81-1.43). There was no significant association between mode of delivery and AD. If children born in a 'repeat C-section' were considered separately the risk of being diagnosed with AR increased further (OR=1.78%, 95% CI=1.34-2.37). The same increase was noted for asthma in girls (OR=1.83%, 95% CI=1.13-2.97) but not in boys. Conclusion Caesarean sections may be associated with an increased risk of developing AR in childhood.	48	115	2005	7	10.1111/j.1365-2222.2005.02356.x	Allergy; Immunology
Food protein-induced enterocolitis syndrome: Case presentations and management lessons. Enterocolitis induced in infants by cow's milk and/or soy protein has been recognized for decades. Symptoms typically begin in the first month of life in association with failure to thrive and may progress to acidemia and shock. Symptoms resolve after the causal protein is removed from the diet but recur with a characteristic symptom pattern on re-exposure. Approximately 2 hours after reintroduction of the protein, vomiting ensues, followed by an elevation of the peripheral blood polymorphonuclear leukocyte count, diarrhea, and possibly lethargy and hypotension. The disorder is generally not associated with detectable food-specific IgE antibody. There are increasing reports of additional causal foods, prolonged clinical courses, and onset outside of early infancy, leading to description of a food protein-induced enterocolitis syndrome. The disorder poses numerous diagnostic and therapeutic challenges. The purpose of this report is to delineate the characteristic clinical features and review the possible pathophysiologic basis to frame a rational strategy toward management.. food allergy| food protein-induced enterocolitis syndrome|cows milk allergy| epithelial barrier function| necrosis-factor-alpha| atopy patch test| gastrointestinal manifestations| clinical-features| skin prick| tnf-alpha| infants| soy.	JAN-2005	food allergy| food protein-induced enterocolitis syndrome|cows milk allergy| epithelial barrier function| necrosis-factor-alpha| atopy patch test| gastrointestinal manifestations| clinical-features| skin prick| tnf-alpha| infants| soy	Sicherer, SH	Food protein-induced enterocolitis syndrome: Case presentations and management lessons		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	food allergy; food protein-induced enterocolitis syndrome	COWS MILK ALLERGY; EPITHELIAL BARRIER FUNCTION; NECROSIS-FACTOR-ALPHA; ATOPY PATCH TEST; GASTROINTESTINAL MANIFESTATIONS; CLINICAL-FEATURES; SKIN PRICK; TNF-ALPHA; INFANTS; SOY	Enterocolitis induced in infants by cow's milk and/or soy protein has been recognized for decades. Symptoms typically begin in the first month of life in association with failure to thrive and may progress to acidemia and shock. Symptoms resolve after the causal protein is removed from the diet but recur with a characteristic symptom pattern on re-exposure. Approximately 2 hours after reintroduction of the protein, vomiting ensues, followed by an elevation of the peripheral blood polymorphonuclear leukocyte count, diarrhea, and possibly lethargy and hypotension. The disorder is generally not associated with detectable food-specific IgE antibody. There are increasing reports of additional causal foods, prolonged clinical courses, and onset outside of early infancy, leading to description of a food protein-induced enterocolitis syndrome. The disorder poses numerous diagnostic and therapeutic challenges. The purpose of this report is to delineate the characteristic clinical features and review the possible pathophysiologic basis to frame a rational strategy toward management.	44	115	2005	8	10.1016/j.jaci.2004.09.033	Allergy; Immunology
Evaluation of impermeable covers for bedding in patients with allergic rhinitis. Background: Encasing bedding in impermeable covers reduces exposure to house-dust mites, but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known. We performed a multicenter, randomized, placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease. Methods: Three participating university medical centers enrolled 279 patients with allergic rhinitis who were randomly assigned to receive impermeable or non-impermeable (control) covers for their mattress, pillow, and duvet or blanket. At the start of the study, all participants received information on general allergen-avoidance measures. The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing. We also measured the concentrations of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f 1) in dust from patients' mattresses, bedroom floors, and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention. Results: A total of 232 patients completed the study. There was a significant reduction in Der p1 and Der f 1 concentrations in the mattresses of the impermeable-cover group, whereas there was no significant reduction in the control group. However, there was no significant effect on the clinical outcome measures. Analyses of subgroups defined according to age, level of exposure, type and severity of sensitization, or characteristics of the patient's home had similar results. Conclusions: Mite-proof bedding covers, as part of a structured allergy-control program, reduced the level of exposure to mite allergens. Despite the success of the intervention, this single avoidance measure did not lead to a significant improvement of clinical symptoms in patients with allergic rhinitis.. house-dust-mite| perennial rhinitis| intranasal capsaicin| mattress encasings| asthmatic-patients| avoidance measures| atopic-dermatitis| cutoff values| double-blind| children.	JUL 17-2003	house-dust-mite| perennial rhinitis| intranasal capsaicin| mattress encasings| asthmatic-patients| avoidance measures| atopic-dermatitis| cutoff values| double-blind| children	Terreehorst, I; Hak, E; Oosting, AJ; Tempels-Pavlica, Z; de Monchy, JGR; Bruijnzeel-Koomen, CAFM; Aalberse, RC; Gerth van Wijk, R	Evaluation of impermeable covers for bedding in patients with allergic rhinitis		NEW ENGLAND JOURNAL OF MEDICINE		HOUSE-DUST-MITE; PERENNIAL RHINITIS; INTRANASAL CAPSAICIN; MATTRESS ENCASINGS; ASTHMATIC-PATIENTS; AVOIDANCE MEASURES; ATOPIC-DERMATITIS; CUTOFF VALUES; DOUBLE-BLIND; CHILDREN	Background: Encasing bedding in impermeable covers reduces exposure to house-dust mites, but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known. We performed a multicenter, randomized, placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease. Methods: Three participating university medical centers enrolled 279 patients with allergic rhinitis who were randomly assigned to receive impermeable or non-impermeable (control) covers for their mattress, pillow, and duvet or blanket. At the start of the study, all participants received information on general allergen-avoidance measures. The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing. We also measured the concentrations of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f 1) in dust from patients' mattresses, bedroom floors, and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention. Results: A total of 232 patients completed the study. There was a significant reduction in Der p1 and Der f 1 concentrations in the mattresses of the impermeable-cover group, whereas there was no significant reduction in the control group. However, there was no significant effect on the clinical outcome measures. Analyses of subgroups defined according to age, level of exposure, type and severity of sensitization, or characteristics of the patient's home had similar results. Conclusions: Mite-proof bedding covers, as part of a structured allergy-control program, reduced the level of exposure to mite allergens. Despite the success of the intervention, this single avoidance measure did not lead to a significant improvement of clinical symptoms in patients with allergic rhinitis.	34	115	2003	10	10.1056/NEJMoa023171	General & Internal Medicine
Hazardous air pollutants and asthma. Asthma has a high prevalence in the United States, and persons with asthma may be at added risk from the adverse effects of hazardous air pollutants (HAPs). Complex mixtures (fine particulate matter and tobacco smoke) have been associated with respiratory symptoms and hospital admissions for asthma. The toxic ingredients of these mixtures are HAPs, but whether ambient HAP exposures. can induce asthma remains unclear. Certain HAPs are occupational asthmagens, whereas others may act as adjuncts during sensitization. HAPs may exacerbate asthma because, once sensitized, individuals can respond to remarkably low concentrations, and irritants lower the bronchoconstrictive threshold to respiratory antigens. Adverse responses after ambient exposures to complex mixtures often occur at concentrations below those producing effects in controlled human exposures to a single compound. In addition, certain HAPs that have been associated with asthma in occupational settings may interact with criteria pollutants in ambient air to exacerbate asthma. Based on these observations and past experience with 188 HAPs, a list of 19 compounds that could have the highest impact on the induction or exacerbation of asthma was developed. Nine additional compounds were identified that might exacerbate asthma based on their irritancy, respirability, or ability to react with biological macromolecules. Although the ambient levels of these 28 compounds are largely unknown, estimated exposures from emissions inventories and limited air monitoring suggest that aldehydes (especially acrolein and formaldehyde) and metals (especially nickel and chromium compounds) may have possible health risk indices sufficient for additional attention. Recommendations for research are presented regarding exposure monitoring and evaluation of biologic mechanisms controlling how these substances induce and exacerbate asthma. Key words: acrolein, aldehydes, asthma, cadmium, chromium, formaldehyde, hazardous air pollutants, metals, nickel, ozone, particulate matter, urban air toxics.. acrolein| aldehydes| asthma| cadmium| chromium| formaldehyde| hazardous air pollutants| metals| nickel| ozone| particulate matter| urban air toxics|volatile organic-compounds| diesel exhaust particles| environmental tobacco-smoke| induced occupational asthma| hydrogen-sulfide exposure| toluene diisocyanate tdi| molecular-weight agents| quantitative trait loci| emergency room visits| human-serum-albumin.	AUG-2002	acrolein| aldehydes| asthma| cadmium| chromium| formaldehyde| hazardous air pollutants| metals| nickel| ozone| particulate matter| urban air toxics|volatile organic-compounds| diesel exhaust particles| environmental tobacco-smoke| induced occupational asthma| hydrogen-sulfide exposure| toluene diisocyanate tdi| molecular-weight agents| quantitative trait loci| emergency room visits| human-serum-albumin	Leikauf, GD	Hazardous air pollutants and asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	acrolein; aldehydes; asthma; cadmium; chromium; formaldehyde; hazardous air pollutants; metals; nickel; ozone; particulate matter; urban air toxics	VOLATILE ORGANIC-COMPOUNDS; DIESEL EXHAUST PARTICLES; ENVIRONMENTAL TOBACCO-SMOKE; INDUCED OCCUPATIONAL ASTHMA; HYDROGEN-SULFIDE EXPOSURE; TOLUENE DIISOCYANATE TDI; MOLECULAR-WEIGHT AGENTS; QUANTITATIVE TRAIT LOCI; EMERGENCY ROOM VISITS; HUMAN-SERUM-ALBUMIN	Asthma has a high prevalence in the United States, and persons with asthma may be at added risk from the adverse effects of hazardous air pollutants (HAPs). Complex mixtures (fine particulate matter and tobacco smoke) have been associated with respiratory symptoms and hospital admissions for asthma. The toxic ingredients of these mixtures are HAPs, but whether ambient HAP exposures. can induce asthma remains unclear. Certain HAPs are occupational asthmagens, whereas others may act as adjuncts during sensitization. HAPs may exacerbate asthma because, once sensitized, individuals can respond to remarkably low concentrations, and irritants lower the bronchoconstrictive threshold to respiratory antigens. Adverse responses after ambient exposures to complex mixtures often occur at concentrations below those producing effects in controlled human exposures to a single compound. In addition, certain HAPs that have been associated with asthma in occupational settings may interact with criteria pollutants in ambient air to exacerbate asthma. Based on these observations and past experience with 188 HAPs, a list of 19 compounds that could have the highest impact on the induction or exacerbation of asthma was developed. Nine additional compounds were identified that might exacerbate asthma based on their irritancy, respirability, or ability to react with biological macromolecules. Although the ambient levels of these 28 compounds are largely unknown, estimated exposures from emissions inventories and limited air monitoring suggest that aldehydes (especially acrolein and formaldehyde) and metals (especially nickel and chromium compounds) may have possible health risk indices sufficient for additional attention. Recommendations for research are presented regarding exposure monitoring and evaluation of biologic mechanisms controlling how these substances induce and exacerbate asthma. Key words: acrolein, aldehydes, asthma, cadmium, chromium, formaldehyde, hazardous air pollutants, metals, nickel, ozone, particulate matter, urban air toxics.	511	115	2002	22		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial. Background Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. Objective To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. Methods A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. Results There were no significant differences between the mimunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3(+) cells (epithelium: P = 0.9. lamina propria: P = 0.2), CD1a(+) cells (P = 0.3, P = 0.25), CD68(+) cells (P = 0.9 P = 1.0) or IL-12 mRNA(+) cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events. Conclusion Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4: IgE ratio, indicates the need for larger, dose-ranging studies.. antibodies| cytokines| hayfever| inummohistochemistry| immunotherapy| rhinoconjunctivitis| sublingual|placebo-controlled trial| standardized 5-grass-pollen extract| parietaria-judaica extract| house-dust-mite| double-blind| swallow immunotherapy| clinical efficacy| induced rhinitis| dendritic cells| oral-mucosa.	APR-2002	antibodies| cytokines| hayfever| inummohistochemistry| immunotherapy| rhinoconjunctivitis| sublingual|placebo-controlled trial| standardized 5-grass-pollen extract| parietaria-judaica extract| house-dust-mite| double-blind| swallow immunotherapy| clinical efficacy| induced rhinitis| dendritic cells| oral-mucosa	Lima, MT; Wilson, D; Pitkin, L; Roberts, A; Nouri-Aria, K; Jacobson, M; Walker, S; Durham, S	Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial		CLINICAL AND EXPERIMENTAL ALLERGY	antibodies; cytokines; hayfever; inummohistochemistry; immunotherapy; rhinoconjunctivitis; sublingual	PLACEBO-CONTROLLED TRIAL; STANDARDIZED 5-GRASS-POLLEN EXTRACT; PARIETARIA-JUDAICA EXTRACT; HOUSE-DUST-MITE; DOUBLE-BLIND; SWALLOW IMMUNOTHERAPY; CLINICAL EFFICACY; INDUCED RHINITIS; DENDRITIC CELLS; ORAL-MUCOSA	Background Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed. Objective To evaluate the efficacy and safety of SLIT in grass pollen-induced seasonal rhinoconjunctivitis. Methods A randomized, placebo-controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen-presenting cells and IL-12 mRNA expression. Results There were no significant differences between the mimunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen-specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3(+) cells (epithelium: P = 0.9. lamina propria: P = 0.2), CD1a(+) cells (P = 0.3, P = 0.25), CD68(+) cells (P = 0.9 P = 1.0) or IL-12 mRNA(+) cells (P = 0.6, P = 0.4). Local side-effects were minor and there were no serious treatment-related adverse events. Conclusion Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4: IgE ratio, indicates the need for larger, dose-ranging studies.	35	115	2002	8	10.1046/j.0954-7894.2002.01327.x	Allergy; Immunology
Corticosteroid-induced improvement in the PC20 of adenosine monophosphate is more closely associated with reduction in airway inflammation than improvement in the PC20 of methacholine. It has been suggested in cross-sectional studies that provocation with adenosine 5'-monophosphate (AMP) more closely reflects the inflammatory process in asthma than does provocation with methacholine or histamine. We investigated whether the steroid-induced improvement in the provocative concentration of AMP producing a 20% decline in FEV1 (PC20 AMP) is more closely associated with the concomitant reduction in airway inflammation than is the improvement in PC20 methacholine. In 120 asthmatic patients, we measured PC20 methacholine and PC20 AMP as well as sputum induction and nitric oxide (NO) in exhaled air before and after 2 weeks of treatment with corticosteroids. Improvement in PC20 AMP was solely related to reduction in airway inflammation (i.e., change in the number of sputum eosinophils, lymphocytes, epithelial cells, and concentration of NO in exhaled air). In contrast, improvement in PC20 methacholine was related to both reduction in airway inflammation (i.e., change in the number of sputum eosinophils and lymphocytes) and increase in FEV1 %predicted. The total explained variance of the improvement in bronchial hyperresponsiveness was greater for AMP than for methacholine (36% versus 22%, respectively). We conclude that PC20 AMP is more sensitive to changes in acute airway inflammation than is PC20 methacholine, further reinforcing the notion that PC20 AMP can be a useful tool for monitoring the effects of antilnflammatory therapy.. adenosine 5 '-monophosphate| hyperresponsiveness| inflammation| asthma| sputum|bronchial biopsy specimens| nitric-oxide| induced bronchoconstriction| inhaled budesonide| asthmatic-patients| atopic asthma| exhaled air| mild asthma| mast-cells| hyperresponsiveness.	OCT 1-2001	adenosine 5 '-monophosphate| hyperresponsiveness| inflammation| asthma| sputum|bronchial biopsy specimens| nitric-oxide| induced bronchoconstriction| inhaled budesonide| asthmatic-patients| atopic asthma| exhaled air| mild asthma| mast-cells| hyperresponsiveness	Van den Berge, M; Kerstjens, HAM; Meijer, RJ; De Reus, DM; Koeter, GH; Kauffman, HF; Postma, DS	Corticosteroid-induced improvement in the PC20 of adenosine monophosphate is more closely associated with reduction in airway inflammation than improvement in the PC20 of methacholine		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	adenosine 5 '-monophosphate; hyperresponsiveness; inflammation; asthma; sputum	BRONCHIAL BIOPSY SPECIMENS; NITRIC-OXIDE; INDUCED BRONCHOCONSTRICTION; INHALED BUDESONIDE; ASTHMATIC-PATIENTS; ATOPIC ASTHMA; EXHALED AIR; MILD ASTHMA; MAST-CELLS; HYPERRESPONSIVENESS	It has been suggested in cross-sectional studies that provocation with adenosine 5'-monophosphate (AMP) more closely reflects the inflammatory process in asthma than does provocation with methacholine or histamine. We investigated whether the steroid-induced improvement in the provocative concentration of AMP producing a 20% decline in FEV1 (PC20 AMP) is more closely associated with the concomitant reduction in airway inflammation than is the improvement in PC20 methacholine. In 120 asthmatic patients, we measured PC20 methacholine and PC20 AMP as well as sputum induction and nitric oxide (NO) in exhaled air before and after 2 weeks of treatment with corticosteroids. Improvement in PC20 AMP was solely related to reduction in airway inflammation (i.e., change in the number of sputum eosinophils, lymphocytes, epithelial cells, and concentration of NO in exhaled air). In contrast, improvement in PC20 methacholine was related to both reduction in airway inflammation (i.e., change in the number of sputum eosinophils and lymphocytes) and increase in FEV1 %predicted. The total explained variance of the improvement in bronchial hyperresponsiveness was greater for AMP than for methacholine (36% versus 22%, respectively). We conclude that PC20 AMP is more sensitive to changes in acute airway inflammation than is PC20 methacholine, further reinforcing the notion that PC20 AMP can be a useful tool for monitoring the effects of antilnflammatory therapy.	40	115	2001	6		General & Internal Medicine; Respiratory System
Respiratory symptoms in European animal farmers. Farmers are known to be at high risk for the development of occupational airway disease. The aim of this European study was to determine which airway symptoms predominate in different types of animal farmers (cattle, pigs, poultry, sheep) and to compare the prevalence of symptoms to the general population. A total of 6,156 randomly selected animal farmers in Denmark, Germany (Schleswig-Holstein, Niedersachsen), Switzerland, and Spain completed a questionnaire on respiratory symptoms and farming characteristics in 1995-1997. The prevalence of general respiratory symptoms was compared to the results of the European Community Respiratory Health Survey (ECRHS) obtained in the same regions. Pig farmers were at highest risk for the development of work-related symptoms. A significant dose-response relationship between daily hours worked inside animal houses and symptoms was established for pig and poultry farmers. Additionally, self-reported nasal allergies (odds ratio (95% confidence interval): 3.92 (3.26-4.71)) and nasal irritation during work (3.98 (3.35-4.73)) were shown to be associated with the development of chronic phlegm. The prevalence of wheezing, shortness of breath, asthma and nasal allergies was significantly lower among all farmers in the age group 20-44 yrs than among the general population. However, the prevalence of usually bringing up phlegm in winter among farmers was significantly higher than in the general population (9.4 (8.3-10.5%) versus 7.5 (6.5-8.5%)). Individual factors have been shown to be related to the prevalence of chronic phlegm among farmers. Additionally, this study could support the hypothesis that farming could be negatively related to allergic diseases.. animal confinement houses| ecrhs| pig farmers| poultry farmers|chronic-bronchitis| dairy farmers| lung-function| hay-fever| sensitization| asthma| dust| prevalence| population| community.	APR-2001	animal confinement houses| ecrhs| pig farmers| poultry farmers|chronic-bronchitis| dairy farmers| lung-function| hay-fever| sensitization| asthma| dust| prevalence| population| community	Radon, K; Danuser, B; Iversen, M; Jorres, R; Monso, E; Opravil, U; Weber, C; Donham, KJ; Nowak, D	Respiratory symptoms in European animal farmers		EUROPEAN RESPIRATORY JOURNAL	animal confinement houses; ECRHS; pig farmers; poultry farmers	CHRONIC-BRONCHITIS; DAIRY FARMERS; LUNG-FUNCTION; HAY-FEVER; SENSITIZATION; ASTHMA; DUST; PREVALENCE; POPULATION; COMMUNITY	Farmers are known to be at high risk for the development of occupational airway disease. The aim of this European study was to determine which airway symptoms predominate in different types of animal farmers (cattle, pigs, poultry, sheep) and to compare the prevalence of symptoms to the general population. A total of 6,156 randomly selected animal farmers in Denmark, Germany (Schleswig-Holstein, Niedersachsen), Switzerland, and Spain completed a questionnaire on respiratory symptoms and farming characteristics in 1995-1997. The prevalence of general respiratory symptoms was compared to the results of the European Community Respiratory Health Survey (ECRHS) obtained in the same regions. Pig farmers were at highest risk for the development of work-related symptoms. A significant dose-response relationship between daily hours worked inside animal houses and symptoms was established for pig and poultry farmers. Additionally, self-reported nasal allergies (odds ratio (95% confidence interval): 3.92 (3.26-4.71)) and nasal irritation during work (3.98 (3.35-4.73)) were shown to be associated with the development of chronic phlegm. The prevalence of wheezing, shortness of breath, asthma and nasal allergies was significantly lower among all farmers in the age group 20-44 yrs than among the general population. However, the prevalence of usually bringing up phlegm in winter among farmers was significantly higher than in the general population (9.4 (8.3-10.5%) versus 7.5 (6.5-8.5%)). Individual factors have been shown to be related to the prevalence of chronic phlegm among farmers. Additionally, this study could support the hypothesis that farming could be negatively related to allergic diseases.	25	115	2001	8	10.1183/09031936.01.17407470	Respiratory System
Elevation of exhaled ethane concentration in asthma. Ethane is a product of lipid peroxidation as a result of oxidative stress and can be detected in the exhaled air. Oxidative stress plays a role in the pathogenesis of asthma. We measured exhaled ethane in 26 asthmatic subjects (mean age +/- SEM, 38 +/- 8 yr; 15 male, FEV1 60 +/- 4%) and compared it with exhaled nitric oxide (NO) measured by chemiluminescence, a noninvasive marker of oxidative stress and inflammation. Exhaled ethane was collected during a flow- and pressure-controlled exhalation into a reservoir discarding dead space air contaminated with ambient air. A sample of the expired air was analyzed by chromatography. Exhaled ethane levels were elevated in asthma patients not receiving steroid (n = 12, 2.06 +/- 0.30 ppb) compared with steroid-treated patients (n = 14, 0.79 +/- 0.70 ppb, p < 0.01) and to 14 nonsmoking control subjects (0.88 +/- 0.09 ppb, p < 0.05). In patients not receiving steroid treatment there was a positive correlation between exhaled ethane and NO (r = 0.55, p < 0.05) and air trapping assessed by the ratio of residual volume to total lung capacity (RV/TLC) (r = 0.60, p < 0.05). In addition, untreated patients with FEV1 < 60% predicted value had higher concentrations of ethane (2.86 +/- 0.37 ppb) compared with less obstructed patients (FEV1 > 60%, 1.26 +/- 0.12 ppb, p < 0.05). NO concentrations were higher in patients not on steroid treatment (14.7 +/- 1.7 ppb) than in steroid-treated patients (8.6 +/- 0.5 ppb, p < 0.05). Exhaled ethane is elevated in asthma, reduced in steroid-treated patients, and correlates with NO and airway obstruction. It may be a useful noninvasive marker of oxidative stress.. smooth-muscle cells| lipid-peroxidation| nitric-oxide| bronchial hyperresponsiveness| oxidative stress| oxygen| glucocorticoids| exhalation| methylprednisolone| inflammation.	OCT-2000	smooth-muscle cells| lipid-peroxidation| nitric-oxide| bronchial hyperresponsiveness| oxidative stress| oxygen| glucocorticoids| exhalation| methylprednisolone| inflammation	Paredi, P; Kharitonov, SA; Barnes, PJ	Elevation of exhaled ethane concentration in asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		SMOOTH-MUSCLE CELLS; LIPID-PEROXIDATION; NITRIC-OXIDE; BRONCHIAL HYPERRESPONSIVENESS; OXIDATIVE STRESS; OXYGEN; GLUCOCORTICOIDS; EXHALATION; METHYLPREDNISOLONE; INFLAMMATION	Ethane is a product of lipid peroxidation as a result of oxidative stress and can be detected in the exhaled air. Oxidative stress plays a role in the pathogenesis of asthma. We measured exhaled ethane in 26 asthmatic subjects (mean age +/- SEM, 38 +/- 8 yr; 15 male, FEV1 60 +/- 4%) and compared it with exhaled nitric oxide (NO) measured by chemiluminescence, a noninvasive marker of oxidative stress and inflammation. Exhaled ethane was collected during a flow- and pressure-controlled exhalation into a reservoir discarding dead space air contaminated with ambient air. A sample of the expired air was analyzed by chromatography. Exhaled ethane levels were elevated in asthma patients not receiving steroid (n = 12, 2.06 +/- 0.30 ppb) compared with steroid-treated patients (n = 14, 0.79 +/- 0.70 ppb, p < 0.01) and to 14 nonsmoking control subjects (0.88 +/- 0.09 ppb, p < 0.05). In patients not receiving steroid treatment there was a positive correlation between exhaled ethane and NO (r = 0.55, p < 0.05) and air trapping assessed by the ratio of residual volume to total lung capacity (RV/TLC) (r = 0.60, p < 0.05). In addition, untreated patients with FEV1 < 60% predicted value had higher concentrations of ethane (2.86 +/- 0.37 ppb) compared with less obstructed patients (FEV1 > 60%, 1.26 +/- 0.12 ppb, p < 0.05). NO concentrations were higher in patients not on steroid treatment (14.7 +/- 1.7 ppb) than in steroid-treated patients (8.6 +/- 0.5 ppb, p < 0.05). Exhaled ethane is elevated in asthma, reduced in steroid-treated patients, and correlates with NO and airway obstruction. It may be a useful noninvasive marker of oxidative stress.	35	115	2000	5		General & Internal Medicine; Respiratory System
Why are some proteins allergens?. The ability of certain proteins to induce an allergic response in susceptible individuals is well established. Symptoms can range from mild erythema or rhinitis, to acute, and possibly fatal, anaphylactic shock. Because such allergic responses require complex interactions between the protein and the immune system, they are notoriously difficult to predict. Nevertheless, it is clear that some proteins are intrinsically more allergenic than others. The challenge for toxicologists is to identify those characteristics that confer on proteins the potential to induce allergic sensitization and allergic disease. Here, we first consider the potential contribution that individual epitopes may make to the allergenicity of a protein. These are the minimal peptide units within proteins that can be recognized by the immune system and are a fundamental requirement for all immune responses, including those resulting in allergic sensitization. It appears that allergens must necessarily contain B-cell epitopes to which immunoglobulin E (IgE) can bind, and T-cell epitopes capable of inducing a type 2 T-lymphocyte response. Nevertheless, it appears doubtful that the presence of appropriate epitopes alone is sufficient to endow a protein with allergenic potential. We therefore consider also the contribution that other features and characteristics of proteins may make to their overall allergenicity. In particular, we consider the effects that resistance to proteolysis, post-translational glycosylation, and enzymatic activity may have. It appears that relative stability in simulated gastric fluid (SGF) sometimes correlates with allergenic activity. However, this is not universally true, and it is known that there are protein allergens, such as some of those associated with oral allergy syndrome, that are unstable. Nevertheless, if stability in SGF is associated with the intrinsic allergenicity of many proteins irrespective of the route of exposure, then this may reflect some more fundamental property of proteins, and possibly their stability in other biologic matrices and/or to intracellular proteases. Post-translational modification appears generally to enhance allergenicity, perhaps by increasing uptake and detection of the protein by the immune system. Some enzymatic activities also enhance allergenicity through what appear to be several different mechanisms, including nonspecific activation of cells participating in the immunologic response. Overall, it appears likely that many factors can contribute to the overall allergenicity of any given protein. Some, such as the presence of epitopes with allergenic potential, may be essential. Others, such as the glycosylation status, resistance to proteolysis, and enzymatic activity, may play a subsidiary but nevertheless critically important role. By better defining the limits within which these factors operate, we can hope to gain a better understanding of the fundamental origins of protein allergenicity, and therefore be in a position to identify and characterize the hazards and risks of allergic disease associated with novel proteins.. allergenicity| epitopes| proteins| simulated gastric fluid (sgf)|altered peptide ligands| house-dust mite| t-cell clones| site-directed mutagenesis| antigen-specific ige| norway rat model| der-p-i| dendritic cells| mannose receptor| major allergen.	JUN-2000	allergenicity| epitopes| proteins| simulated gastric fluid (sgf)|altered peptide ligands| house-dust mite| t-cell clones| site-directed mutagenesis| antigen-specific ige| norway rat model| der-p-i| dendritic cells| mannose receptor| major allergen	Huby, RDJ; Dearman, RJ; Kimber, I	Why are some proteins allergens?		TOXICOLOGICAL SCIENCES	allergenicity; epitopes; proteins; simulated gastric fluid (SGF)	ALTERED PEPTIDE LIGANDS; HOUSE-DUST MITE; T-CELL CLONES; SITE-DIRECTED MUTAGENESIS; ANTIGEN-SPECIFIC IGE; NORWAY RAT MODEL; DER-P-I; DENDRITIC CELLS; MANNOSE RECEPTOR; MAJOR ALLERGEN	The ability of certain proteins to induce an allergic response in susceptible individuals is well established. Symptoms can range from mild erythema or rhinitis, to acute, and possibly fatal, anaphylactic shock. Because such allergic responses require complex interactions between the protein and the immune system, they are notoriously difficult to predict. Nevertheless, it is clear that some proteins are intrinsically more allergenic than others. The challenge for toxicologists is to identify those characteristics that confer on proteins the potential to induce allergic sensitization and allergic disease. Here, we first consider the potential contribution that individual epitopes may make to the allergenicity of a protein. These are the minimal peptide units within proteins that can be recognized by the immune system and are a fundamental requirement for all immune responses, including those resulting in allergic sensitization. It appears that allergens must necessarily contain B-cell epitopes to which immunoglobulin E (IgE) can bind, and T-cell epitopes capable of inducing a type 2 T-lymphocyte response. Nevertheless, it appears doubtful that the presence of appropriate epitopes alone is sufficient to endow a protein with allergenic potential. We therefore consider also the contribution that other features and characteristics of proteins may make to their overall allergenicity. In particular, we consider the effects that resistance to proteolysis, post-translational glycosylation, and enzymatic activity may have. It appears that relative stability in simulated gastric fluid (SGF) sometimes correlates with allergenic activity. However, this is not universally true, and it is known that there are protein allergens, such as some of those associated with oral allergy syndrome, that are unstable. Nevertheless, if stability in SGF is associated with the intrinsic allergenicity of many proteins irrespective of the route of exposure, then this may reflect some more fundamental property of proteins, and possibly their stability in other biologic matrices and/or to intracellular proteases. Post-translational modification appears generally to enhance allergenicity, perhaps by increasing uptake and detection of the protein by the immune system. Some enzymatic activities also enhance allergenicity through what appear to be several different mechanisms, including nonspecific activation of cells participating in the immunologic response. Overall, it appears likely that many factors can contribute to the overall allergenicity of any given protein. Some, such as the presence of epitopes with allergenic potential, may be essential. Others, such as the glycosylation status, resistance to proteolysis, and enzymatic activity, may play a subsidiary but nevertheless critically important role. By better defining the limits within which these factors operate, we can hope to gain a better understanding of the fundamental origins of protein allergenicity, and therefore be in a position to identify and characterize the hazards and risks of allergic disease associated with novel proteins.	141	115	2000	12	10.1093/toxsci/55.2.235	Toxicology
Endocrine Disruptors and Asthma-Associated Chemicals in Consumer Products. BACKGROUND: Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. OBJECTIVES: We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. METHODS: We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters. RESULTS: We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels. CONCLUSIONS: Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in product composition. Consumers should be able to avoid some target chemicals-synthetic fragrances, BPA, and regulated active ingredients-using purchasing criteria. More complete product labeling would enable consumers to avoid the rest of the target chemicals.. alkylphenols| asthma| bisphenol a| consumer products| cyclosiloxane| endocrine disruptors| fragrance compounds| parabens| phthalates| uv filters|polybrominated diphenyl ethers| prenatal phthalate exposure| personal care products| sprague-dawley rat| occupational asthma| cosmetic products| polycyclic musks| bisphenol-a| uv filters| indoor air.	JUL-2012	alkylphenols| asthma| bisphenol a| consumer products| cyclosiloxane| endocrine disruptors| fragrance compounds| parabens| phthalates| uv filters|polybrominated diphenyl ethers| prenatal phthalate exposure| personal care products| sprague-dawley rat| occupational asthma| cosmetic products| polycyclic musks| bisphenol-a| uv filters| indoor air	Dodson, RE; Nishioka, M; Standley, LJ; Perovich, LJ; Brody, JG; Rudel, RA	Endocrine Disruptors and Asthma-Associated Chemicals in Consumer Products		ENVIRONMENTAL HEALTH PERSPECTIVES	alkylphenols; asthma; bisphenol A; consumer products; cyclosiloxane; endocrine disruptors; fragrance compounds; parabens; phthalates; UV filters	POLYBROMINATED DIPHENYL ETHERS; PRENATAL PHTHALATE EXPOSURE; PERSONAL CARE PRODUCTS; SPRAGUE-DAWLEY RAT; OCCUPATIONAL ASTHMA; COSMETIC PRODUCTS; POLYCYCLIC MUSKS; BISPHENOL-A; UV FILTERS; INDOOR AIR	BACKGROUND: Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. OBJECTIVES: We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. METHODS: We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters. RESULTS: We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels. CONCLUSIONS: Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in product composition. Consumers should be able to avoid some target chemicals-synthetic fragrances, BPA, and regulated active ingredients-using purchasing criteria. More complete product labeling would enable consumers to avoid the rest of the target chemicals.	104	114	2012	9	10.1289/ehp.1104052	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity. Background: Asthma has been considered an immunologic disease mediated by T(H)2 cells and adaptive immunity. However, clinical and experimental observations suggest that additional pathways might regulate asthma, particularly in its nonallergic forms, such as asthma associated with air pollution, stress, obesity, and infection. Objectives: Our goal was to understand T(H)2 cell-independent conditions that might lead to airway hyperreactivity (AHR), a cardinal feature of asthma. Methods: We examined a murine model of experimental asthma in which AHR was induced with glycolipid antigens, which activate natural killer T (NKT) cells. Results: In this model AHR developed rapidly when mice were treated with NKT cell-activating glycolipid antigens, even in the absence of conventional CD4(+) T cells. The activated NKT cells directly induced alveolar macrophages to produce IL-33, which in turn activated NKT cells, as well as natural helper cells, a newly described non-T, non-B, innate lymphoid cell type, to increase production of IL-13. Surprisingly, this glycolipid-induced AHR pathway required not only IL-13 but also IL-33 and its receptor, ST2, because it was blocked by an anti-ST2 mAb and was greatly reduced in ST2(-/-) mice. When adoptively transferred into IL-13(-/-) mice, both wild-type natural helper cells and NKT cells were sufficient for the development of glycolipid-induced AHR. Conclusion: Because plant pollens, house dust, and some bacteria contain glycolipids that can directly activate NKT cells, these studies suggest that AHR and asthma can fully develop or be greatly enhanced through innate immune mechanisms involving IL-33, natural helper cells, and NKT cells. (J Allergy Clin Immunol 2012;129:216-27.). innate| natural killer t| natural helper cells| t(h)2| il-33| il-13| glycolipid| asthma|killer t-cells| invariant nkt cells| in-vivo| rheumatoid-arthritis| experimental asthma| type-2 immunity| inflammation| receptor| expression| responses.	JAN-2012	innate| natural killer t| natural helper cells| t(h)2| il-33| il-13| glycolipid| asthma|killer t-cells| invariant nkt cells| in-vivo| rheumatoid-arthritis| experimental asthma| type-2 immunity| inflammation| receptor| expression| responses	Kim, HY; Chang, YJ; Subramanian, S; Lee, HH; Albacker, LA; Matangkasombut, P; Savage, PB; McKenzie, ANJ; Smith, DE; Rottman, JB; DeKruyff, RH; Umetsu, DT	Innate lymphoid cells responding to IL-33 mediate airway hyperreactivity independently of adaptive immunity		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Innate; natural killer T; natural helper cells; T(H)2; IL-33; IL-13; glycolipid; asthma	KILLER T-CELLS; INVARIANT NKT CELLS; IN-VIVO; RHEUMATOID-ARTHRITIS; EXPERIMENTAL ASTHMA; TYPE-2 IMMUNITY; INFLAMMATION; RECEPTOR; EXPRESSION; RESPONSES	Background: Asthma has been considered an immunologic disease mediated by T(H)2 cells and adaptive immunity. However, clinical and experimental observations suggest that additional pathways might regulate asthma, particularly in its nonallergic forms, such as asthma associated with air pollution, stress, obesity, and infection. Objectives: Our goal was to understand T(H)2 cell-independent conditions that might lead to airway hyperreactivity (AHR), a cardinal feature of asthma. Methods: We examined a murine model of experimental asthma in which AHR was induced with glycolipid antigens, which activate natural killer T (NKT) cells. Results: In this model AHR developed rapidly when mice were treated with NKT cell-activating glycolipid antigens, even in the absence of conventional CD4(+) T cells. The activated NKT cells directly induced alveolar macrophages to produce IL-33, which in turn activated NKT cells, as well as natural helper cells, a newly described non-T, non-B, innate lymphoid cell type, to increase production of IL-13. Surprisingly, this glycolipid-induced AHR pathway required not only IL-13 but also IL-33 and its receptor, ST2, because it was blocked by an anti-ST2 mAb and was greatly reduced in ST2(-/-) mice. When adoptively transferred into IL-13(-/-) mice, both wild-type natural helper cells and NKT cells were sufficient for the development of glycolipid-induced AHR. Conclusion: Because plant pollens, house dust, and some bacteria contain glycolipids that can directly activate NKT cells, these studies suggest that AHR and asthma can fully develop or be greatly enhanced through innate immune mechanisms involving IL-33, natural helper cells, and NKT cells. (J Allergy Clin Immunol 2012;129:216-27.)	56	114	2012	18	10.1016/j.jaci.2011.10.036	Allergy; Immunology
Short-term Associations between Ambient Air Pollutants and Pediatric Asthma Emergency Department Visits. Rationale: Certain outdoor air pollutants cause asthma exacerbations in children. To advance understanding of these relationships, further characterization of the dose-response and pollutant lag effects are needed, as are investigations of pollutant species beyond the commonly measured criteria pollutants. Objectives: Investigate short-term associations between ambient air pollutant concentrations and emergency department visits for pediatric asthma. Methods: Daily counts of emergency department visits for asthma or wheeze among children aged 5 to 17 years were collected from 41 Metropolitan Atlanta hospitals during 1993-2004 (n = 91,386 visits). Ambient concentrations of gaseous pollutants and speciated particulate matter were available from stationary monitors during this time period Rate ratios for the warm season (May to October) and cold season (November to April) were estimated using Poisson generalized linear models in the framework of a case-crossover analysis Measurements and Main Results: Both ozone and primary pollutants from traffic sources were associated with emergency department visits for asthma or wheeze; evidence for independent effects of ozone and primary pollutants from traffic sources were observed in multipollutant models. These associations tended to be of the highest magnitude for concentrations on the day of the emergency department visit and were present at relatively low ambient concentrations. Conclusions. Even at relatively low ambient concentrations, ozone and primary pollutants from traffic sources independently contributed to the burden of emergency department visits for pediatric asthma. ambient particulate matter, asthma| minors| ozone|southeastern united-states| case-crossover analyses| fine particulate matter| time-series methods| source apportionment| spatial variability| referent selection| aerosol research| organic-carbon| daily deaths.	AUG 1-2010	ambient particulate matter, asthma| minors| ozone|southeastern united-states| case-crossover analyses| fine particulate matter| time-series methods| source apportionment| spatial variability| referent selection| aerosol research| organic-carbon| daily deaths	Strickland, MJ; Darrow, LA; Klein, M; Flanders, WD; Sarnat, JA; Waller, LA; Sarnat, SE; Mulholland, JA; Tolbert, PE	Short-term Associations between Ambient Air Pollutants and Pediatric Asthma Emergency Department Visits		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	ambient particulate matter, asthma; minors; ozone	SOUTHEASTERN UNITED-STATES; CASE-CROSSOVER ANALYSES; FINE PARTICULATE MATTER; TIME-SERIES METHODS; SOURCE APPORTIONMENT; SPATIAL VARIABILITY; REFERENT SELECTION; AEROSOL RESEARCH; ORGANIC-CARBON; DAILY DEATHS	Rationale: Certain outdoor air pollutants cause asthma exacerbations in children. To advance understanding of these relationships, further characterization of the dose-response and pollutant lag effects are needed, as are investigations of pollutant species beyond the commonly measured criteria pollutants. Objectives: Investigate short-term associations between ambient air pollutant concentrations and emergency department visits for pediatric asthma. Methods: Daily counts of emergency department visits for asthma or wheeze among children aged 5 to 17 years were collected from 41 Metropolitan Atlanta hospitals during 1993-2004 (n = 91,386 visits). Ambient concentrations of gaseous pollutants and speciated particulate matter were available from stationary monitors during this time period Rate ratios for the warm season (May to October) and cold season (November to April) were estimated using Poisson generalized linear models in the framework of a case-crossover analysis Measurements and Main Results: Both ozone and primary pollutants from traffic sources were associated with emergency department visits for asthma or wheeze; evidence for independent effects of ozone and primary pollutants from traffic sources were observed in multipollutant models. These associations tended to be of the highest magnitude for concentrations on the day of the emergency department visit and were present at relatively low ambient concentrations. Conclusions. Even at relatively low ambient concentrations, ozone and primary pollutants from traffic sources independently contributed to the burden of emergency department visits for pediatric asthma	54	114	2010	10	10.1164/rccm.200908-1201OC	General & Internal Medicine; Respiratory System
Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity. Allergic contact hypersensitivity (CHS) is a T cell-mediated inflammatory skin disease. Interleukin (IL)-12 is considered to be important in the generation of the allergen-specific T cell response. Loss of IL-12 function in IL-12R beta 2-deficient mice, however, did not ameliorate the allergic immune response, suggesting alternate IL-12-independent pathways in the induction of CHS. Because exposure to contact allergens always takes place in the presence of microbial skin flora, we investigated the potential role of Toll-like receptors (TLRs) in the induction of CHS. Using mice deficient in TLR4, the receptor for bacterial lipopolysaccharide (LPS), IL-12 receptor (R) beta 2, or both, we show that the concomitant absence of TLR4 and IL-12R beta 2, but not the absence of TLR4 or IL-12R beta 2 alone, prevented DC-mediated sensitization, generation of effector T cells, and the subsequent CHS response to 2,4,6-trinitro-1-chlorobenzene (TNCB), oxazolone, and fluorescein isothiocyanate. Introduction of the TLR4 transgene into the TLR4/IL-12R beta 2 mutant restored the CHS inducibility, showing a requirement for TLR4 in IL-12-independent CHS induction. Furthermore, the concomitant absence of TLR2 and TLR4 prevented the induction of CHS to TNCB in IL-12-competent mice. Finally, CHS was inducible in germ-free wild-type and IL-12R beta 2-deficient mice, but not in germ-free TLR4/IL-12R beta 2 double deficient mice, suggesting that the necessary TLR activation may proceed via endogenous ligands.. activated protein-kinase| cd8(+) t-cells| dendritic cells| ifn-alpha| immune-responses| cutting edge| fluorescein isothiocyanate| sensitizer trinitrophenyl| mediated inhibition| c57bl/10sccr mice.	SEP 1-2008	activated protein-kinase| cd8(+) t-cells| dendritic cells| ifn-alpha| immune-responses| cutting edge| fluorescein isothiocyanate| sensitizer trinitrophenyl| mediated inhibition| c57bl/10sccr mice	Martin, SF; Dudda, JC; Bachtanian, E; Lembo, A; Liller, S; Durr, C; Heimesaat, MM; Bereswill, S; Fejer, G; Vassileva, R; Jakob, T; Freudenberg, N; Termeer, CC; Johner, C; Galanos, C; Freudenberg, MA	Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity		JOURNAL OF EXPERIMENTAL MEDICINE		ACTIVATED PROTEIN-KINASE; CD8(+) T-CELLS; DENDRITIC CELLS; IFN-ALPHA; IMMUNE-RESPONSES; CUTTING EDGE; FLUORESCEIN ISOTHIOCYANATE; SENSITIZER TRINITROPHENYL; MEDIATED INHIBITION; C57BL/10SCCR MICE	Allergic contact hypersensitivity (CHS) is a T cell-mediated inflammatory skin disease. Interleukin (IL)-12 is considered to be important in the generation of the allergen-specific T cell response. Loss of IL-12 function in IL-12R beta 2-deficient mice, however, did not ameliorate the allergic immune response, suggesting alternate IL-12-independent pathways in the induction of CHS. Because exposure to contact allergens always takes place in the presence of microbial skin flora, we investigated the potential role of Toll-like receptors (TLRs) in the induction of CHS. Using mice deficient in TLR4, the receptor for bacterial lipopolysaccharide (LPS), IL-12 receptor (R) beta 2, or both, we show that the concomitant absence of TLR4 and IL-12R beta 2, but not the absence of TLR4 or IL-12R beta 2 alone, prevented DC-mediated sensitization, generation of effector T cells, and the subsequent CHS response to 2,4,6-trinitro-1-chlorobenzene (TNCB), oxazolone, and fluorescein isothiocyanate. Introduction of the TLR4 transgene into the TLR4/IL-12R beta 2 mutant restored the CHS inducibility, showing a requirement for TLR4 in IL-12-independent CHS induction. Furthermore, the concomitant absence of TLR2 and TLR4 prevented the induction of CHS to TNCB in IL-12-competent mice. Finally, CHS was inducible in germ-free wild-type and IL-12R beta 2-deficient mice, but not in germ-free TLR4/IL-12R beta 2 double deficient mice, suggesting that the necessary TLR activation may proceed via endogenous ligands.	66	114	2008	12	10.1084/jem.20070509	Immunology; Research & Experimental Medicine
Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression. Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF-beta-producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J chain-containing) Abs to the major allergen Phi p 5 were determined by ELISA before and after a 2-year double-blind trial of grass pollen (Phleum pratense) injection IT. Nasal TGF-beta expression was assessed by in situ hybridization. Sera from five IT patients were fractionated for functional analysis of the effects of IgA and IgG Abs on IL-10 production by blood monocytes and allergen-IgE binding to B cells. Serum Phi p 5-specific IgA2 Abs increased after a 2-year treatment (similar to 8-fold increase, p = 0.002) in contrast to IgA1. Increases in polymeric Abs to Phi p 5 (similar to 2-fold increase,p = 0.02) and in nasal TGF-beta mRNA (p = 0.05) were also observed, and TGF-beta mRNA correlated with serum Phi p 5 IgA2 (r = 0.61,p = 0.009). Post-IT IgA fractions triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding to B cells as observed with IgG fractions. This study shows for the first time that the IgA response to IT is selective for IgA2, correlates with increased local TGF-beta expression, and induces monocyte IL-10 expression, suggesting that IgA Abs could thereby contribute to the tolerance developed in IT-treated allergic patients.. growth-factor-beta| messenger-rna expression| t-cell differentiation| venom immunotherapy| dendritic cells| b-cells| igg antibodies| secretory iga| house-dust| interleukin-10.	APR 1-2007	growth-factor-beta| messenger-rna expression| t-cell differentiation| venom immunotherapy| dendritic cells| b-cells| igg antibodies| secretory iga| house-dust| interleukin-10	Pilette, C; Nouri-Aria, KT; Jacobson, MR; Wilcock, LK; Detry, B; Walker, SM; Francis, JN; Durham, SR	Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression		JOURNAL OF IMMUNOLOGY		GROWTH-FACTOR-BETA; MESSENGER-RNA EXPRESSION; T-CELL DIFFERENTIATION; VENOM IMMUNOTHERAPY; DENDRITIC CELLS; B-CELLS; IGG ANTIBODIES; SECRETORY IGA; HOUSE-DUST; INTERLEUKIN-10	Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF-beta-producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J chain-containing) Abs to the major allergen Phi p 5 were determined by ELISA before and after a 2-year double-blind trial of grass pollen (Phleum pratense) injection IT. Nasal TGF-beta expression was assessed by in situ hybridization. Sera from five IT patients were fractionated for functional analysis of the effects of IgA and IgG Abs on IL-10 production by blood monocytes and allergen-IgE binding to B cells. Serum Phi p 5-specific IgA2 Abs increased after a 2-year treatment (similar to 8-fold increase, p = 0.002) in contrast to IgA1. Increases in polymeric Abs to Phi p 5 (similar to 2-fold increase,p = 0.02) and in nasal TGF-beta mRNA (p = 0.05) were also observed, and TGF-beta mRNA correlated with serum Phi p 5 IgA2 (r = 0.61,p = 0.009). Post-IT IgA fractions triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding to B cells as observed with IgG fractions. This study shows for the first time that the IgA response to IT is selective for IgA2, correlates with increased local TGF-beta expression, and induces monocyte IL-10 expression, suggesting that IgA Abs could thereby contribute to the tolerance developed in IT-treated allergic patients.	52	114	2007	9		Immunology
Oral glucocorticoid use is associated with an increased risk of fracture. Oral glucocorticoids (GCs) are widely used and despite their adverse effects on bone mineral density, the risk of sustaining osteoporotic fractures is not well addressed. The objective of this retrospective, cohort study was to assess fracture risk in patients exposed to oral GCs. Patients from an administrative claims database who were prescribed oral GCs and were enrolled 1 year before and 1 year after the initial oral GC claim were matched with a comparison population on age, sex, and date of first claim. Measurements of exposure included amount, duration, and pattern of oral GC use. The osteoporosis-related risk of fracture was based on the ratio of hazard functions estimated using a Cox proportional hazards model. The adjusted relative risk (RR) estimates (and 95% CI) for fractures were hip 1.87 (95% CI, 1.2 to 2.9), vertebral 2.92 (95% CI, 2.0 to 4.3), wrist/forearm 1.03 (95% CI, 0.8 to 1.4), nonvertebral 1.68 (95% CI, 1.5 to 1.9), any fracture 1.75 (95% CI, 1.6 to 1.9). A dose dependence of fracture risk was observed for hip, vertebral, nonvertebral, and any fractures. Long duration and continuous pattern of GC use demonstrated a significant 5-fold increased risk of hip and 5.9-fold increased risk of vertebral fracture. The combined effect of higher dose, longer duration, and continuous pattern further increased RR estimates to 7-fold for hip and 17-fold for vertebral fractures. This study confirms previous observations that suggest oral GCs have a rapid deleterious effect on trabecular-rich bone. The emerging relationship between amount, duration, and pattern of oral GC exposure and fracture risk should be considered in clinical practice and managed care settings to avoid the debilitating effects of fractures in patients.. epidemiology| fracture| oral glucocorticoids| osteoporosis|low-dose corticosteroids| rheumatoid-arthritis patients| bone-mineral density| induced osteoporosis| vertebral fractures| induced osteopenia| therapy| asthma| mass| spine.	APR-2004	epidemiology| fracture| oral glucocorticoids| osteoporosis|low-dose corticosteroids| rheumatoid-arthritis patients| bone-mineral density| induced osteoporosis| vertebral fractures| induced osteopenia| therapy| asthma| mass| spine	Steinbuch, M; Youket, TE; Cohen, S	Oral glucocorticoid use is associated with an increased risk of fracture		OSTEOPOROSIS INTERNATIONAL	epidemiology; fracture; oral glucocorticoids; osteoporosis	LOW-DOSE CORTICOSTEROIDS; RHEUMATOID-ARTHRITIS PATIENTS; BONE-MINERAL DENSITY; INDUCED OSTEOPOROSIS; VERTEBRAL FRACTURES; INDUCED OSTEOPENIA; THERAPY; ASTHMA; MASS; SPINE	Oral glucocorticoids (GCs) are widely used and despite their adverse effects on bone mineral density, the risk of sustaining osteoporotic fractures is not well addressed. The objective of this retrospective, cohort study was to assess fracture risk in patients exposed to oral GCs. Patients from an administrative claims database who were prescribed oral GCs and were enrolled 1 year before and 1 year after the initial oral GC claim were matched with a comparison population on age, sex, and date of first claim. Measurements of exposure included amount, duration, and pattern of oral GC use. The osteoporosis-related risk of fracture was based on the ratio of hazard functions estimated using a Cox proportional hazards model. The adjusted relative risk (RR) estimates (and 95% CI) for fractures were hip 1.87 (95% CI, 1.2 to 2.9), vertebral 2.92 (95% CI, 2.0 to 4.3), wrist/forearm 1.03 (95% CI, 0.8 to 1.4), nonvertebral 1.68 (95% CI, 1.5 to 1.9), any fracture 1.75 (95% CI, 1.6 to 1.9). A dose dependence of fracture risk was observed for hip, vertebral, nonvertebral, and any fractures. Long duration and continuous pattern of GC use demonstrated a significant 5-fold increased risk of hip and 5.9-fold increased risk of vertebral fracture. The combined effect of higher dose, longer duration, and continuous pattern further increased RR estimates to 7-fold for hip and 17-fold for vertebral fractures. This study confirms previous observations that suggest oral GCs have a rapid deleterious effect on trabecular-rich bone. The emerging relationship between amount, duration, and pattern of oral GC exposure and fracture risk should be considered in clinical practice and managed care settings to avoid the debilitating effects of fractures in patients.	28	114	2004	6	10.1007/s00198-003-1548-3	Endocrinology & Metabolism
T helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1 cells. T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated, Th2-biased peripheral immune response appears to be an important pathogenetic factor. In atopic dermatitis, circulating cutaneous lymphocyte-associated antigen-bearing (CLA(+)) CD45RO(+) T cells with skin-specific homing property represent an activated memory/effector T cell subset. They express high levels of Fas and Fas ligand and undergo activation-induced apoptosis. The freshly purified (CLA(+)) CD45RO(+) T cells of atopic individuals display distinct features of in vivo-triggered apoptosis such as procaspase degradation and active caspase-8 formation. In particular, the Th1 compartment of activated memory/effector T cells selectively undergoes activation-induced cell death, skewing the immune response toward surviving Th2 cells in atopic dermatitis patients. The apoptosis of circulating memory/effector T cells was confined to atopic individuals whereas non-atopic patients such as psoriasis, intrinsic-type asthma, contact dermatitis, intrinsic type of atopic dermatitis, bee venom allergic patients, and healthy controls showed no evidence for enhanced T cell apoptosis in vivo. These results define a novel mechanism for peripheral Th2 response in atopic diseases.. activation-induced cell death| atopic dermatitis| cytokines| t cells| th1/th2|lymphocyte-associated antigen| activation-induced apoptosis| fas-mediated apoptosis| signaling complex| heca-452 epitope| in-vivo| dermatitis| death| expression| skin.	JUN-2003	activation-induced cell death| atopic dermatitis| cytokines| t cells| th1/th2|lymphocyte-associated antigen| activation-induced apoptosis| fas-mediated apoptosis| signaling complex| heca-452 epitope| in-vivo| dermatitis| death| expression| skin	Akdis, M; Trautmann, A; Klunker, S; Daigle, I; Kucuksezer, UC; Deglmann, W; Disch, R; Blaser, K; Akdis, CA	T helper (Th) 2 predominance in atopic diseases is due to preferential apoptosis of circulating memory/effector Th1 cells		FASEB JOURNAL	activation-induced cell death; atopic dermatitis; cytokines; T cells; Th1/Th2	LYMPHOCYTE-ASSOCIATED ANTIGEN; ACTIVATION-INDUCED APOPTOSIS; FAS-MEDIATED APOPTOSIS; SIGNALING COMPLEX; HECA-452 EPITOPE; IN-VIVO; DERMATITIS; DEATH; EXPRESSION; SKIN	T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated, Th2-biased peripheral immune response appears to be an important pathogenetic factor. In atopic dermatitis, circulating cutaneous lymphocyte-associated antigen-bearing (CLA(+)) CD45RO(+) T cells with skin-specific homing property represent an activated memory/effector T cell subset. They express high levels of Fas and Fas ligand and undergo activation-induced apoptosis. The freshly purified (CLA(+)) CD45RO(+) T cells of atopic individuals display distinct features of in vivo-triggered apoptosis such as procaspase degradation and active caspase-8 formation. In particular, the Th1 compartment of activated memory/effector T cells selectively undergoes activation-induced cell death, skewing the immune response toward surviving Th2 cells in atopic dermatitis patients. The apoptosis of circulating memory/effector T cells was confined to atopic individuals whereas non-atopic patients such as psoriasis, intrinsic-type asthma, contact dermatitis, intrinsic type of atopic dermatitis, bee venom allergic patients, and healthy controls showed no evidence for enhanced T cell apoptosis in vivo. These results define a novel mechanism for peripheral Th2 response in atopic diseases.	55	114	2003	10	10.1096/fj.02-1070com	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology
Paracetamol use in pregnancy and wheezing in early childhood. Background: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18-20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30-42 months (n=9400) and eczema at 18-30 months (n=10 2 16) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at <6 months and at 30-42 months) were examined. Results: Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20-32 weeks), but not in early pregnancy (<18-20 weeks), was associated with an increased risk of wheezing in the offspring at 30-42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% Cl 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% Cl 1.24 to 4.40); P=0.008). Assuming a causal relation, only about 1% of wheezing at 30-42 months was attributable to this exposure. Frequent paracetomol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months. Conclusions: Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.. glutathione s-transferase| atopic disease| risk-factors| human-fetal| asthma| acetaminophen| lung| children| mouse| life.	NOV-2002	glutathione s-transferase| atopic disease| risk-factors| human-fetal| asthma| acetaminophen| lung| children| mouse| life	Shaheen, SO; Newson, RB; Sherriff, A; Henderson, AJ; Heron, JE; Burney, PGJ; Golding, J	Paracetamol use in pregnancy and wheezing in early childhood		THORAX		GLUTATHIONE S-TRANSFERASE; ATOPIC DISEASE; RISK-FACTORS; HUMAN-FETAL; ASTHMA; ACETAMINOPHEN; LUNG; CHILDREN; MOUSE; LIFE	Background: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18-20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30-42 months (n=9400) and eczema at 18-30 months (n=10 2 16) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at <6 months and at 30-42 months) were examined. Results: Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20-32 weeks), but not in early pregnancy (<18-20 weeks), was associated with an increased risk of wheezing in the offspring at 30-42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% Cl 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% Cl 1.24 to 4.40); P=0.008). Assuming a causal relation, only about 1% of wheezing at 30-42 months was attributable to this exposure. Frequent paracetomol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months. Conclusions: Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.	35	114	2002	6	10.1136/thorax.57.11.958	Respiratory System
Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices. The Ca2+ signaling and contractility of airway smooth Muscle cells (SMCs) were investigated with confocal microscopy in murine lung slices (similar to75-mum thick) that maintained the in situ organization of the airways and the contractility of the SMCs for at least 5 d. 10-500 nM acetylcholine (ACH) induced a contraction of the air- way lumen and a transient increase in [Ca2+], in individual SMCs that subsequently declined to initiate multiple intracellular Ca2+ oscillations. These Ca2+ oscillations spread as Ca2+ waves through the SMCs at similar to48 mum/s. The magnitude of the airway contraction, the initial Ca2+ transient, and the frequency of the subsequent Ca2+ oscillations were all concentration-dependent. In a Ca2+-free solution, ACH induced a similar Ca2+ response, except that the Ca2+ oscillations ceased after 1-1.5 min. Incubation with thapsigargin, xestospongin, or ryanodine inhibited the ACH-induced Ca2+ signaling. A comparison of airway contraction with the ACH-induced Ca2+ response of the SMCs revealed that the onset of airway contraction correlated with the initial Ca2+ transient, and that sustained airway contraction correlated with the occurrence of the Ca2+ oscillations. Buffering intracellular Ca2+ with BATIA prohibited Ca2+ signaling and airway contraction, indicating a Ca2+-dependent pathway. Cessation of the Ca2+ oscillations, induced by ACH-esterase, halothane, or the absence of extracellular Ca2+ resulted in a relaxation of the airways The concentration dependence of the airway contraction matched the concentration dependeuce of the increased frequency of the Ca2+ oscillations. These results indicate that Ca2+ oscillations, induced by ACH in murine bronchial SMCs, are generated by Ca2+ release from the SR involving IPs and ryanodine receptors, and are required to maintain airway contraction.. asthma| hyper-reactivity| confocal microscopy| ca2+ oscillations| frequency modulation|individual airways| responsiveness| heterogeneity| methacholine| transduction| rat| oscillations| responses| explants| channels.	FEB-2002	asthma| hyper-reactivity| confocal microscopy| ca2+ oscillations| frequency modulation|individual airways| responsiveness| heterogeneity| methacholine| transduction| rat| oscillations| responses| explants| channels	Bergner, A; Sanderson, MJ	Acetylcholine-induced calcium signaling and contraction of airway smooth muscle cells in lung slices		JOURNAL OF GENERAL PHYSIOLOGY	asthma; hyper-reactivity; confocal microscopy; Ca2+ oscillations; frequency modulation	INDIVIDUAL AIRWAYS; RESPONSIVENESS; HETEROGENEITY; METHACHOLINE; TRANSDUCTION; RAT; OSCILLATIONS; RESPONSES; EXPLANTS; CHANNELS	The Ca2+ signaling and contractility of airway smooth Muscle cells (SMCs) were investigated with confocal microscopy in murine lung slices (similar to75-mum thick) that maintained the in situ organization of the airways and the contractility of the SMCs for at least 5 d. 10-500 nM acetylcholine (ACH) induced a contraction of the air- way lumen and a transient increase in [Ca2+], in individual SMCs that subsequently declined to initiate multiple intracellular Ca2+ oscillations. These Ca2+ oscillations spread as Ca2+ waves through the SMCs at similar to48 mum/s. The magnitude of the airway contraction, the initial Ca2+ transient, and the frequency of the subsequent Ca2+ oscillations were all concentration-dependent. In a Ca2+-free solution, ACH induced a similar Ca2+ response, except that the Ca2+ oscillations ceased after 1-1.5 min. Incubation with thapsigargin, xestospongin, or ryanodine inhibited the ACH-induced Ca2+ signaling. A comparison of airway contraction with the ACH-induced Ca2+ response of the SMCs revealed that the onset of airway contraction correlated with the initial Ca2+ transient, and that sustained airway contraction correlated with the occurrence of the Ca2+ oscillations. Buffering intracellular Ca2+ with BATIA prohibited Ca2+ signaling and airway contraction, indicating a Ca2+-dependent pathway. Cessation of the Ca2+ oscillations, induced by ACH-esterase, halothane, or the absence of extracellular Ca2+ resulted in a relaxation of the airways The concentration dependence of the airway contraction matched the concentration dependeuce of the increased frequency of the Ca2+ oscillations. These results indicate that Ca2+ oscillations, induced by ACH in murine bronchial SMCs, are generated by Ca2+ release from the SR involving IPs and ryanodine receptors, and are required to maintain airway contraction.	32	114	2002	12	10.1085/jgp.119.2.187	Physiology
Allergic contact dermatitis. Allergic contact dermatitis (ACD) is a common occupational and environmental health issue. In common with other forms of allergy the disease progresses in two stages; an initial phase during which sensitization is acquired, followed later (after subsequent exposure to the same chemical allergen) by elicitation of a cutaneous inflammatory reaction. The development of skin sensitization is associated with, and requires, the activation and clonal expansion of allergen responsive T lymphocytes and it is these cells that orchestrate the cutaneous allergic reaction. In recent years, much has been: learned of the characteristics of immune responses to skin sensitizing chemicals and of the roles played by dendritic cells, cytokines and chemokines. Some of the more interesting cellular and molecular mechanisms are reviewed briefly in this article. A more detailed appreciation of responses induced by chemical allergens has in turn facilitated the design of novel approaches to the toxicological evaluation of skin sensitization. Real progress has been made, not only in the development of improved methods for hazard identification and characterization, but also in the application of new paradigms for risk assessment. The newer methods now available and the opportunities that exist for further advances are considered. Finally, progress has been made in the characterization of skin sensitization in humans and in the clinical management of ACD. This article seeks to consider skin sensitization and ACD in holistic fashion, bridging experimental observations with clinical disease and basic mechanisms with practical toxicology. (C) 2002 Elsevier Science B.V. All rights reserved.. allergic contact dermatitis| skin sensitization| hazard identification| risk assessment| langerhans cells| t lymphocytes|lymph-node assay| cd8(+) t-cells| cytokine secretion profiles| skin sensitization risk| chemical allergens| effector cd8(+)| langerhans cells| cd4(+)| mice| hypersensitivity.	FEB-2002	allergic contact dermatitis| skin sensitization| hazard identification| risk assessment| langerhans cells| t lymphocytes|lymph-node assay| cd8(+) t-cells| cytokine secretion profiles| skin sensitization risk| chemical allergens| effector cd8(+)| langerhans cells| cd4(+)| mice| hypersensitivity	Kimber, I; Basketter, DA; Gerberick, GF; Dearman, RJ	Allergic contact dermatitis		INTERNATIONAL IMMUNOPHARMACOLOGY	allergic contact dermatitis; skin sensitization; hazard identification; risk assessment; Langerhans cells; T lymphocytes	LYMPH-NODE ASSAY; CD8(+) T-CELLS; CYTOKINE SECRETION PROFILES; SKIN SENSITIZATION RISK; CHEMICAL ALLERGENS; EFFECTOR CD8(+); LANGERHANS CELLS; CD4(+); MICE; HYPERSENSITIVITY	Allergic contact dermatitis (ACD) is a common occupational and environmental health issue. In common with other forms of allergy the disease progresses in two stages; an initial phase during which sensitization is acquired, followed later (after subsequent exposure to the same chemical allergen) by elicitation of a cutaneous inflammatory reaction. The development of skin sensitization is associated with, and requires, the activation and clonal expansion of allergen responsive T lymphocytes and it is these cells that orchestrate the cutaneous allergic reaction. In recent years, much has been: learned of the characteristics of immune responses to skin sensitizing chemicals and of the roles played by dendritic cells, cytokines and chemokines. Some of the more interesting cellular and molecular mechanisms are reviewed briefly in this article. A more detailed appreciation of responses induced by chemical allergens has in turn facilitated the design of novel approaches to the toxicological evaluation of skin sensitization. Real progress has been made, not only in the development of improved methods for hazard identification and characterization, but also in the application of new paradigms for risk assessment. The newer methods now available and the opportunities that exist for further advances are considered. Finally, progress has been made in the characterization of skin sensitization in humans and in the clinical management of ACD. This article seeks to consider skin sensitization and ACD in holistic fashion, bridging experimental observations with clinical disease and basic mechanisms with practical toxicology. (C) 2002 Elsevier Science B.V. All rights reserved.	71	114	2002	11	10.1016/S1567-5769(01)00173-4	Immunology; Pharmacology & Pharmacy
Diesel exhaust particles directly induce activated mast cells to degranulate and increase histamine levels and symptom severity. Background: The ability of combustion products, such as diesel exhaust particles (DEPs), to modulate the immune system has now been firmly established. DEPs can synergize with allergen at the human upper respiratory mucosa to enhance allergen-specific IgE production, initiate a T(H)2 cytokine environment, and even promote primary allergic sensitization. Experiments suggest that these effects result from the initial activation of mast cells to produce IL-4. Objective: We sought to demonstrate that in vivo mast cell activation by DEPs plus allergen will also affect the release of classic mast cell mediators and consequently enhance the immediate-phase response. Methods: Dust mite-sensitive subjects were challenged intranasally with allergen, and symptom scores and histamine levels in nasal wash samples were compared after prechallenge with 0.3 mg of DEPs, Results: If the subjects were first sprayed with DEPs, mean symptom scores rose from 3.7 to 9.9; additionally, only one fifth of the amount of intranasal dust mite allergen was required to induce clinical symptoms. DEPs alone had no effect. The changes in symptoms correlated with histamine levels measured in nasal lavage specimens from these subjects, Although challenge with DEPs alone did not induce histamine release, challenge with both DEPs and allergen resulted in 3-fold higher histamine concentrations than those seen with allergen alone. In contrast, carbon black particles (elemental carbon devoid of chemicals) had no effect. The role of chemicals was confirmed because degranulation of a murine mast cell fine by Fc epsilon RI cross-linking was increased significantly (by 72%) by the soluble organic chemicals extracted from DEPs. Conclusions: Overall, these results suggest that exposure to DEPs can enhance the severity of clinical symptoms to allergen by enhancing mast cell degranulation.. allergy| pollution| mediators| clinical outcomes| hypersensitivity|in-vivo| ige production| cytokine production| mercuric-chloride| ragweed allergen| messenger-rna| dry air| release| challenge| il-4.	DEC-2000	allergy| pollution| mediators| clinical outcomes| hypersensitivity|in-vivo| ige production| cytokine production| mercuric-chloride| ragweed allergen| messenger-rna| dry air| release| challenge| il-4	Diaz-Sanchez, D; Penichet-Garcia, M; Saxon, A	Diesel exhaust particles directly induce activated mast cells to degranulate and increase histamine levels and symptom severity		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; pollution; mediators; clinical outcomes; hypersensitivity	IN-VIVO; IGE PRODUCTION; CYTOKINE PRODUCTION; MERCURIC-CHLORIDE; RAGWEED ALLERGEN; MESSENGER-RNA; DRY AIR; RELEASE; CHALLENGE; IL-4	Background: The ability of combustion products, such as diesel exhaust particles (DEPs), to modulate the immune system has now been firmly established. DEPs can synergize with allergen at the human upper respiratory mucosa to enhance allergen-specific IgE production, initiate a T(H)2 cytokine environment, and even promote primary allergic sensitization. Experiments suggest that these effects result from the initial activation of mast cells to produce IL-4. Objective: We sought to demonstrate that in vivo mast cell activation by DEPs plus allergen will also affect the release of classic mast cell mediators and consequently enhance the immediate-phase response. Methods: Dust mite-sensitive subjects were challenged intranasally with allergen, and symptom scores and histamine levels in nasal wash samples were compared after prechallenge with 0.3 mg of DEPs, Results: If the subjects were first sprayed with DEPs, mean symptom scores rose from 3.7 to 9.9; additionally, only one fifth of the amount of intranasal dust mite allergen was required to induce clinical symptoms. DEPs alone had no effect. The changes in symptoms correlated with histamine levels measured in nasal lavage specimens from these subjects, Although challenge with DEPs alone did not induce histamine release, challenge with both DEPs and allergen resulted in 3-fold higher histamine concentrations than those seen with allergen alone. In contrast, carbon black particles (elemental carbon devoid of chemicals) had no effect. The role of chemicals was confirmed because degranulation of a murine mast cell fine by Fc epsilon RI cross-linking was increased significantly (by 72%) by the soluble organic chemicals extracted from DEPs. Conclusions: Overall, these results suggest that exposure to DEPs can enhance the severity of clinical symptoms to allergen by enhancing mast cell degranulation.	38	114	2000	7	10.1067/mai.2000.111144	Allergy; Immunology
Mouse allergen. I. The prevalence of mouse allergen in inner-city homes. Background: Although mouse allergen is a well-defined cause of IgE-mediated hypersensitivity in occupational settings, it has not been web studied in the general population. Objective: We sought to determine the prevalence of mouse allergen in inner-city homes. Methods: A subset of 608 homes from the National Cooperative Inner-City Asthma Study population had dust samples adequate for analysis of mouse allergen. In addition, data regarding the demographics and housing of the subjects were related to the mouse allergen levels. Results: Ninety-five percent of all homes had detectable mouse allergen (Mus m 1) in at least one room, with the highest levels found in kitchens (kitchen: range, 0-618 mug/g; median, 1.60 mug/g; bedroom: range, 0-294 mug/g; median, 0.52 mug/g; television-living room: range, 0-203 mug/g; median, 0.57 mug/g). By city, 100% of the kitchens in Baltimore had detectable mouse allergen, with the lowest percentage (74%) in Cleveland Mouse allergen levels correlated among rooms (R = 0.65-0.75). Forty-nine percent of the homes had reported problems with mice within the last year, and 29% of the homes had evidence of mice in one or more rooms on home inspection and had higher levels of mouse allergen (P = .0001). Higher allergen levels were also associated with evidence of cockroach infestation in any room (P = .006), None of the other subject or housing demographics evaluated were associated with a higher prevalence or level of mouse allergen. Conclusions: We conclude that mouse allergen is widely distributed in inner-city homes and that cockroach infestation is associated with high mouse allergen levels.. mouse allergen| indoor allergens| inner-city asthma| sensitization|cockroach allergen| house dust| asthma| children| exposure| mite| sensitization| cat.	DEC-2000	mouse allergen| indoor allergens| inner-city asthma| sensitization|cockroach allergen| house dust| asthma| children| exposure| mite| sensitization| cat	Phipatanakul, W; Eggleston, PA; Wright, EC; Wood, RA	Mouse allergen. I. The prevalence of mouse allergen in inner-city homes		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	mouse allergen; indoor allergens; inner-city asthma; sensitization	COCKROACH ALLERGEN; HOUSE DUST; ASTHMA; CHILDREN; EXPOSURE; MITE; SENSITIZATION; CAT	Background: Although mouse allergen is a well-defined cause of IgE-mediated hypersensitivity in occupational settings, it has not been web studied in the general population. Objective: We sought to determine the prevalence of mouse allergen in inner-city homes. Methods: A subset of 608 homes from the National Cooperative Inner-City Asthma Study population had dust samples adequate for analysis of mouse allergen. In addition, data regarding the demographics and housing of the subjects were related to the mouse allergen levels. Results: Ninety-five percent of all homes had detectable mouse allergen (Mus m 1) in at least one room, with the highest levels found in kitchens (kitchen: range, 0-618 mug/g; median, 1.60 mug/g; bedroom: range, 0-294 mug/g; median, 0.52 mug/g; television-living room: range, 0-203 mug/g; median, 0.57 mug/g). By city, 100% of the kitchens in Baltimore had detectable mouse allergen, with the lowest percentage (74%) in Cleveland Mouse allergen levels correlated among rooms (R = 0.65-0.75). Forty-nine percent of the homes had reported problems with mice within the last year, and 29% of the homes had evidence of mice in one or more rooms on home inspection and had higher levels of mouse allergen (P = .0001). Higher allergen levels were also associated with evidence of cockroach infestation in any room (P = .006), None of the other subject or housing demographics evaluated were associated with a higher prevalence or level of mouse allergen. Conclusions: We conclude that mouse allergen is widely distributed in inner-city homes and that cockroach infestation is associated with high mouse allergen levels.	18	114	2000	5		Allergy; Immunology
Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment. The kinetics of airway inflammation and remodeling processes following ovalbumin aerosol challenge in sensitized BALB/c mice was studied. Mice were exposed to either single or five ovalbumin challenges over 5 days. In both protocols, time-dependent increases in bronchoalveolar lavage (BAL) cellular fibronectin, neutrophils and eosinophils were observed. The kinetics of these events were similar in both protocols; however, the magnitude of the response was much greater following repeated challenges. BAL protein levels and lymphocyte numbers were increased only following repeated challenges, whereas interleukin (IL)-5 and IL-4 were increased in both protocols. Histological analysis revealed a time-dependent increase in epithelial cell proliferation and in mucus-producing epithelial cells. Proliferation of alveolar cells was observed only following repeated challenges. Airway hyperreactivity was observed in both protocols but was much greater following repeated challenges. Pretreatment with dexamethasone fully inhibited the inflammatory response and airway hyperreactivity but only partially inhibited the remodeling process. These data suggest that glucocorticoids, although potent anti-inflammatory agents, may not be potent in reducing the lung remodeling process associated with asthma.. airway hyperreactivity| dexamethasone| eosinophils|subepithelial fibrosis| airway inflammation| bronchial-asthma| smooth-muscle| allergen| responsiveness| hyperresponsiveness| hyperreactivity| responses| exposure.	DEC-2000	airway hyperreactivity| dexamethasone| eosinophils|subepithelial fibrosis| airway inflammation| bronchial-asthma| smooth-muscle| allergen| responsiveness| hyperresponsiveness| hyperreactivity| responses| exposure	Trifilieff, A; El-Hashim, A; Bertrand, C	Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment		AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY	airway hyperreactivity; dexamethasone; eosinophils	SUBEPITHELIAL FIBROSIS; AIRWAY INFLAMMATION; BRONCHIAL-ASTHMA; SMOOTH-MUSCLE; ALLERGEN; RESPONSIVENESS; HYPERRESPONSIVENESS; HYPERREACTIVITY; RESPONSES; EXPOSURE	The kinetics of airway inflammation and remodeling processes following ovalbumin aerosol challenge in sensitized BALB/c mice was studied. Mice were exposed to either single or five ovalbumin challenges over 5 days. In both protocols, time-dependent increases in bronchoalveolar lavage (BAL) cellular fibronectin, neutrophils and eosinophils were observed. The kinetics of these events were similar in both protocols; however, the magnitude of the response was much greater following repeated challenges. BAL protein levels and lymphocyte numbers were increased only following repeated challenges, whereas interleukin (IL)-5 and IL-4 were increased in both protocols. Histological analysis revealed a time-dependent increase in epithelial cell proliferation and in mucus-producing epithelial cells. Proliferation of alveolar cells was observed only following repeated challenges. Airway hyperreactivity was observed in both protocols but was much greater following repeated challenges. Pretreatment with dexamethasone fully inhibited the inflammatory response and airway hyperreactivity but only partially inhibited the remodeling process. These data suggest that glucocorticoids, although potent anti-inflammatory agents, may not be potent in reducing the lung remodeling process associated with asthma.	27	114	2000	9		Physiology; Respiratory System
Development of an asthma specific job exposure matrix and its application in the epidemiological study of genetics and environment in asthma (EGEA). Objectives-To develop a method suitable for estimating exposure risks in population studies of asthma from job titles and international codes, by combining a new job exposure matrix (JEM) with the expert judgement approach. The method was applied in the French epidemiological study of the genetics and environment in asthma (EGEA). Methods-The JEM contains 22 exposure groups including 18 high risk groups based on known risk factors for occupational asthma, divided into high molecular weight agents, low molecular weight agents, and mixed environments. After applying the JEM to job codes, exposure estimates for each subject were reevaluated by examining job title texts. Three high risk exposure estimates for asthma were compared: firstly, applying the JEM to original codes (from different coders in each study centre); secondly, applying the JEM to revised codes (from one experienced coder); and thirdly, after reviewing JEM exposure estimates in the light of job title texts. Results-The study comprised 173 cases with asthma and 285 controls (age 18-65). Odds ratios (ORs) for asthma for high risk jobs were 1.0 (95% confidence interval (95% CI) 0.6 to 1.7), applying the JEM to original codes; 1.4 (95% CI 0.8 to 2.3), applying the JEM to revised codes; and 1.7 (95% CI 1.1 to 2.7), applying the JEM and subsequently re-evaluating exposure estimates from job title texts. Asthma ORs were 1.4 (95% CI 0.6 to 2.9) for high molecular weight agents, 2.3 (95% CI 1.2 to 4.4) for low molecular weight agents, and 2.1 (95% CI 0.9 to 5.2) for mixed environments. Conclusions-This asthma JEM, when enhanced by expert re-evaluation of exposure estimates from job title texts, may be a useful tool in general population studies of asthma. In this study, a 1.7-fold increase in prevalence odds of high risk exposures was found among asthmatic workers compared with controls, with risk magnitude varying for different classes of exposure.. job exposure matrix| asthma| occupational exposure| epidemiological methods| case-control|occupational case-control| work histories| information| reliability| zutphen| cohort| atopy.	SEP-2000	job exposure matrix| asthma| occupational exposure| epidemiological methods| case-control|occupational case-control| work histories| information| reliability| zutphen| cohort| atopy	Kennedy, SM; Le Moual, N; Choudat, D; Kauffmann, F	Development of an asthma specific job exposure matrix and its application in the epidemiological study of genetics and environment in asthma (EGEA)		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE	job exposure matrix; asthma; occupational exposure; epidemiological methods; case-control	OCCUPATIONAL CASE-CONTROL; WORK HISTORIES; INFORMATION; RELIABILITY; ZUTPHEN; COHORT; ATOPY	Objectives-To develop a method suitable for estimating exposure risks in population studies of asthma from job titles and international codes, by combining a new job exposure matrix (JEM) with the expert judgement approach. The method was applied in the French epidemiological study of the genetics and environment in asthma (EGEA). Methods-The JEM contains 22 exposure groups including 18 high risk groups based on known risk factors for occupational asthma, divided into high molecular weight agents, low molecular weight agents, and mixed environments. After applying the JEM to job codes, exposure estimates for each subject were reevaluated by examining job title texts. Three high risk exposure estimates for asthma were compared: firstly, applying the JEM to original codes (from different coders in each study centre); secondly, applying the JEM to revised codes (from one experienced coder); and thirdly, after reviewing JEM exposure estimates in the light of job title texts. Results-The study comprised 173 cases with asthma and 285 controls (age 18-65). Odds ratios (ORs) for asthma for high risk jobs were 1.0 (95% confidence interval (95% CI) 0.6 to 1.7), applying the JEM to original codes; 1.4 (95% CI 0.8 to 2.3), applying the JEM to revised codes; and 1.7 (95% CI 1.1 to 2.7), applying the JEM and subsequently re-evaluating exposure estimates from job title texts. Asthma ORs were 1.4 (95% CI 0.6 to 2.9) for high molecular weight agents, 2.3 (95% CI 1.2 to 4.4) for low molecular weight agents, and 2.1 (95% CI 0.9 to 5.2) for mixed environments. Conclusions-This asthma JEM, when enhanced by expert re-evaluation of exposure estimates from job title texts, may be a useful tool in general population studies of asthma. In this study, a 1.7-fold increase in prevalence odds of high risk exposures was found among asthmatic workers compared with controls, with risk magnitude varying for different classes of exposure.	25	114	2000	7	10.1136/oem.57.9.635	Public, Environmental & Occupational Health
Outdoor air pollution and asthma. Traffic and power generation are the main sources of urban air pollution. The idea that outdoor air pollution can cause exacerbations of pre-existing asthma is supported by an evidence base that has been accumulating for several decades, with several studies suggesting a contribution to new-onset asthma as well. In this Series paper, we discuss the effects of particulate matter (PM), gaseous pollutants (ozone, nitrogen dioxide, and sulphur dioxide), and mixed traffic-related air pollution. We focus on clinical studies, both epidemiological and experimental, published in the previous 5 years. From a mechanistic perspective, air pollutants probably cause oxidative injury to the airways, leading to inflammation, remodelling, and increased risk of sensitisation. Although several pollutants have been linked to new-onset asthma, the strength of the evidence is variable. We also discuss clinical implications, policy issues, and research gaps relevant to air pollution and asthma.. diesel exhaust particles| tobacco-smoke exposure| emergency-department visits| ambient particulate matter| nitrogen-dioxide exposure| exhaled nitric-oxide| new-york-city| childhood asthma| lung-function| oxidative stress.	MAY 3-2014	diesel exhaust particles| tobacco-smoke exposure| emergency-department visits| ambient particulate matter| nitrogen-dioxide exposure| exhaled nitric-oxide| new-york-city| childhood asthma| lung-function| oxidative stress	Guarnieri, M; Balmes, JR	Outdoor air pollution and asthma		LANCET		DIESEL EXHAUST PARTICLES; TOBACCO-SMOKE EXPOSURE; EMERGENCY-DEPARTMENT VISITS; AMBIENT PARTICULATE MATTER; NITROGEN-DIOXIDE EXPOSURE; EXHALED NITRIC-OXIDE; NEW-YORK-CITY; CHILDHOOD ASTHMA; LUNG-FUNCTION; OXIDATIVE STRESS	Traffic and power generation are the main sources of urban air pollution. The idea that outdoor air pollution can cause exacerbations of pre-existing asthma is supported by an evidence base that has been accumulating for several decades, with several studies suggesting a contribution to new-onset asthma as well. In this Series paper, we discuss the effects of particulate matter (PM), gaseous pollutants (ozone, nitrogen dioxide, and sulphur dioxide), and mixed traffic-related air pollution. We focus on clinical studies, both epidemiological and experimental, published in the previous 5 years. From a mechanistic perspective, air pollutants probably cause oxidative injury to the airways, leading to inflammation, remodelling, and increased risk of sensitisation. Although several pollutants have been linked to new-onset asthma, the strength of the evidence is variable. We also discuss clinical implications, policy issues, and research gaps relevant to air pollution and asthma.	139	113	2014	12		General & Internal Medicine
Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma A Systematic Review. Importance Allergic rhinitis affects up to 40% of the US population. To desensitize allergic individuals, subcutaneous injection immunotherapy or sublingual immunotherapy may be administered. In the United States, sublingual immunotherapy is not approved by the Food and Drug Administration. However, some US physicians use aqueous allergens, off-label, for sublingual desensitization. Objective To systematically review the effectiveness and safety of aqueous sublingual immunotherapy for allergic rhinoconjunctivitis and asthma. Evidence Acquisition The databases of MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials were searched through December 22, 2012. English-language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens and reported clinical outcomes. Studies of sublingual immunotherapy that are unavailable in the United States and for which a related immunotherapy is unavailable in the United States were excluded. Paired reviewers selected articles and extracted the data. The strength of the evidence for each comparison and outcome was graded based on the risk of bias (scored on allocation, concealment of intervention, incomplete data, sponsor company involvement, and other bias), consistency, magnitude of effect, and the directness of the evidence. Results Sixty-three studies with 5131 participants met the inclusion criteria. Participants' ages ranged from 4 to 74 years. Twenty studies (n=1814 patients) enrolled only children. The risk of bias was medium in 43 studies (68%). Strong evidence supports that sublingual immunotherapy improves asthma symptoms, with 8 of 13 studies reporting greater than40% improvement vs the comparator. Moderate evidence supports that sublingual immunotherapy use decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies demonstrating greater than 40% improvement vs the comparator. Medication use for asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual immunotherapy with moderate grade evidence. Moderate evidence supports that sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined symptom and medication scores (20 studies), and disease-specific quality of life (8 studies). Local reactions were frequent, but anaphylaxis was not reported. Conclusions and Relevance The overall evidence provides a moderate grade level of evidence to support the effectiveness of sublingual immunotherapy for the treatment of allergic rhinitis and asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies. There were limitations in the standardization of adverse events reporting, but no life-threatening adverse events were noted in this review. JAMA. 2013; 309(12): 1278-1288 www.jama.com. placebo-controlled trial| double-blind placebo| randomized controlled-trial| grass-pollen extract| house-dust-mite| parietaria-judaica extract| japanese cedar pollinosis| quality-of-life| swallow immunotherapy| respiratory allergy.	MAR 27-2013	placebo-controlled trial| double-blind placebo| randomized controlled-trial| grass-pollen extract| house-dust-mite| parietaria-judaica extract| japanese cedar pollinosis| quality-of-life| swallow immunotherapy| respiratory allergy	Lin, SY; Erekosima, N; Kim, JM; Ramanathan, M; Suarez-Cuervo, C; Chelladurai, Y; Ward, D; Segal, JB	Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma A Systematic Review		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND PLACEBO; RANDOMIZED CONTROLLED-TRIAL; GRASS-POLLEN EXTRACT; HOUSE-DUST-MITE; PARIETARIA-JUDAICA EXTRACT; JAPANESE CEDAR POLLINOSIS; QUALITY-OF-LIFE; SWALLOW IMMUNOTHERAPY; RESPIRATORY ALLERGY	Importance Allergic rhinitis affects up to 40% of the US population. To desensitize allergic individuals, subcutaneous injection immunotherapy or sublingual immunotherapy may be administered. In the United States, sublingual immunotherapy is not approved by the Food and Drug Administration. However, some US physicians use aqueous allergens, off-label, for sublingual desensitization. Objective To systematically review the effectiveness and safety of aqueous sublingual immunotherapy for allergic rhinoconjunctivitis and asthma. Evidence Acquisition The databases of MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials were searched through December 22, 2012. English-language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens and reported clinical outcomes. Studies of sublingual immunotherapy that are unavailable in the United States and for which a related immunotherapy is unavailable in the United States were excluded. Paired reviewers selected articles and extracted the data. The strength of the evidence for each comparison and outcome was graded based on the risk of bias (scored on allocation, concealment of intervention, incomplete data, sponsor company involvement, and other bias), consistency, magnitude of effect, and the directness of the evidence. Results Sixty-three studies with 5131 participants met the inclusion criteria. Participants' ages ranged from 4 to 74 years. Twenty studies (n=1814 patients) enrolled only children. The risk of bias was medium in 43 studies (68%). Strong evidence supports that sublingual immunotherapy improves asthma symptoms, with 8 of 13 studies reporting greater than40% improvement vs the comparator. Moderate evidence supports that sublingual immunotherapy use decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies demonstrating greater than 40% improvement vs the comparator. Medication use for asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual immunotherapy with moderate grade evidence. Moderate evidence supports that sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined symptom and medication scores (20 studies), and disease-specific quality of life (8 studies). Local reactions were frequent, but anaphylaxis was not reported. Conclusions and Relevance The overall evidence provides a moderate grade level of evidence to support the effectiveness of sublingual immunotherapy for the treatment of allergic rhinitis and asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies. There were limitations in the standardization of adverse events reporting, but no life-threatening adverse events were noted in this review. JAMA. 2013; 309(12): 1278-1288 www.jama.com	91	113	2013	11	10.1001/jama.2013.2049	General & Internal Medicine
Response to self antigen imprints regulatory memory in tissues. Immune homeostasis in tissues is achieved through a delicate balance between pathogenic T-cell responses directed at tissue-specific antigens and the ability of the tissue to inhibit these responses. The mechanisms by which tissues and the immune system communicate to establish and maintain immune homeostasis are currently unknown. Clinical evidence suggests that chronic or repeated exposure to self antigen within tissues leads to an attenuation of pathological autoimmune responses, possibly as a means to mitigate inflammatory damage and preserve function. Many human organ-specific autoimmune diseases are characterized by the initial presentation of the disease being the most severe, with subsequent flares being of lesser severity and duration(1). In fact, these diseases often spontaneously resolve, despite persistent tissue autoantigen expression(2). In the practice of antigen-specific immunotherapy, allergens or self antigens are repeatedly injected in the skin, with a diminution of the inflammatory response occurring after each successive exposure(3). Although these findings indicate that tissues acquire the ability to attenuate autoimmune reactions upon repeated responses to antigens, the mechanism by which this occurs is unknown. Here we show that upon expression of self antigen in a peripheral tissue, thymus-derived regulatory T cells (T-reg cells) become activated, proliferate and differentiate into more potent suppressors, which mediate resolution of organ-specific autoimmunity in mice. After resolution of the inflammatory response, activated T-reg cells are maintained in the target tissue and are primed to attenuate subsequent autoimmune reactions when antigen is re-expressed. Thus, T-reg cells function to confer 'regulatory memory' to the target tissue. These findings provide a framework for understanding how T-reg cells respond when exposed to self antigen in peripheral tissues and offer mechanistic insight into how tissues regulate autoimmunity.. t-cells| in-vivo| expression| autoantigen| homeostasis| autoimmune| depletion| diseases| mice.	DEC 22-2011	t-cells| in-vivo| expression| autoantigen| homeostasis| autoimmune| depletion| diseases| mice	Rosenblum, MD; Gratz, IK; Paw, JS; Lee, K; Marshak-Rothstein, A; Abbas, AK	Response to self antigen imprints regulatory memory in tissues		NATURE		T-CELLS; IN-VIVO; EXPRESSION; AUTOANTIGEN; HOMEOSTASIS; AUTOIMMUNE; DEPLETION; DISEASES; MICE	Immune homeostasis in tissues is achieved through a delicate balance between pathogenic T-cell responses directed at tissue-specific antigens and the ability of the tissue to inhibit these responses. The mechanisms by which tissues and the immune system communicate to establish and maintain immune homeostasis are currently unknown. Clinical evidence suggests that chronic or repeated exposure to self antigen within tissues leads to an attenuation of pathological autoimmune responses, possibly as a means to mitigate inflammatory damage and preserve function. Many human organ-specific autoimmune diseases are characterized by the initial presentation of the disease being the most severe, with subsequent flares being of lesser severity and duration(1). In fact, these diseases often spontaneously resolve, despite persistent tissue autoantigen expression(2). In the practice of antigen-specific immunotherapy, allergens or self antigens are repeatedly injected in the skin, with a diminution of the inflammatory response occurring after each successive exposure(3). Although these findings indicate that tissues acquire the ability to attenuate autoimmune reactions upon repeated responses to antigens, the mechanism by which this occurs is unknown. Here we show that upon expression of self antigen in a peripheral tissue, thymus-derived regulatory T cells (T-reg cells) become activated, proliferate and differentiate into more potent suppressors, which mediate resolution of organ-specific autoimmunity in mice. After resolution of the inflammatory response, activated T-reg cells are maintained in the target tissue and are primed to attenuate subsequent autoimmune reactions when antigen is re-expressed. Thus, T-reg cells function to confer 'regulatory memory' to the target tissue. These findings provide a framework for understanding how T-reg cells respond when exposed to self antigen in peripheral tissues and offer mechanistic insight into how tissues regulate autoimmunity.	17	113	2011	6	10.1038/nature10664	Science & Technology - Other Topics
Metal Allergy-A Review on Exposures, Penetration, Genetics, Prevalence, and Clinical Implications. The prevalence of metal allergy is high in the general population, and it is estimated that up to 17% of women and 3% of men are allergic to nickel and that 1-3% are allergic to cobalt and chromium. Among dermatitis patients, the prevalence of metal allergy is even higher. Metal allergy is mainly an environmental disorder although null Mutations in the filaggrin gene complex were recently found to be associated with nickel allergy and dermatitis. Environmental metal exposures include jewelry, buttons, clothing fasteners, dental restorations, mobile phones, and leather. Although consumer exposure is responsible for most cases of metal allergy, the importance Of Occupational metal exposure remains present and should always be taken into consideration when one interprets allergic patch test reactions to metals. Traditionally, nickel, cobalt, and chromium have been the most important contact allergens. However, recently, gold and palladium have drawn much attention as the prevalence of contact allergy to these metals is high. Palladium allergy is mainly a result of cross-sensitization to nickel, whereas gold allergy is rarely clinically relevant when one takes its high prevalence into account. The epidemiology of metal allergy has recently changed in Europe as nickel allergy among ear-pierced Danish women has decreased following regulatory intervention oil nickel release from consumer products. In the United States, the prevalence of nickel allergy is still increasing, which may be explained by the absence of regulation. The prevalence of chromium allergy is increasing in the United States, Singapore, and Denmark among dermatitis patients. This increase is significantly associated with leather exposure in Denmark. Metal allergy may result in allergic contact dermatitis and systemic allergic (contact) dematitis. Furthermore, metal allergy has been associated with device failure following insertion of intracoronary stents, hip and knee prostheses, as well as other implants. This area is in need of more research.. occupational contact-dermatitis| unselected danish population| patch test concentrations| gold sodium thiosulfate| total hip-arthroplasty| in-stent restenosis| nickel allergy| on-metal| orthopedic implants| ferrous sulfate.	FEB-2010	occupational contact-dermatitis| unselected danish population| patch test concentrations| gold sodium thiosulfate| total hip-arthroplasty| in-stent restenosis| nickel allergy| on-metal| orthopedic implants| ferrous sulfate	Thyssen, JP; Menne, T	Metal Allergy-A Review on Exposures, Penetration, Genetics, Prevalence, and Clinical Implications		CHEMICAL RESEARCH IN TOXICOLOGY		OCCUPATIONAL CONTACT-DERMATITIS; UNSELECTED DANISH POPULATION; PATCH TEST CONCENTRATIONS; GOLD SODIUM THIOSULFATE; TOTAL HIP-ARTHROPLASTY; IN-STENT RESTENOSIS; NICKEL ALLERGY; ON-METAL; ORTHOPEDIC IMPLANTS; FERROUS SULFATE	The prevalence of metal allergy is high in the general population, and it is estimated that up to 17% of women and 3% of men are allergic to nickel and that 1-3% are allergic to cobalt and chromium. Among dermatitis patients, the prevalence of metal allergy is even higher. Metal allergy is mainly an environmental disorder although null Mutations in the filaggrin gene complex were recently found to be associated with nickel allergy and dermatitis. Environmental metal exposures include jewelry, buttons, clothing fasteners, dental restorations, mobile phones, and leather. Although consumer exposure is responsible for most cases of metal allergy, the importance Of Occupational metal exposure remains present and should always be taken into consideration when one interprets allergic patch test reactions to metals. Traditionally, nickel, cobalt, and chromium have been the most important contact allergens. However, recently, gold and palladium have drawn much attention as the prevalence of contact allergy to these metals is high. Palladium allergy is mainly a result of cross-sensitization to nickel, whereas gold allergy is rarely clinically relevant when one takes its high prevalence into account. The epidemiology of metal allergy has recently changed in Europe as nickel allergy among ear-pierced Danish women has decreased following regulatory intervention oil nickel release from consumer products. In the United States, the prevalence of nickel allergy is still increasing, which may be explained by the absence of regulation. The prevalence of chromium allergy is increasing in the United States, Singapore, and Denmark among dermatitis patients. This increase is significantly associated with leather exposure in Denmark. Metal allergy may result in allergic contact dermatitis and systemic allergic (contact) dematitis. Furthermore, metal allergy has been associated with device failure following insertion of intracoronary stents, hip and knee prostheses, as well as other implants. This area is in need of more research.	185	113	2010	10	10.1021/tx9002726	Pharmacology & Pharmacy; Chemistry; Toxicology
Mothers' anxiety during pregnancy is associated with asthma in their children. Background: Maternal stress in early life has been associated with the development of asthma in children, although it is unclear whether there are any critical periods of exposure. The association of asthma with prenatal exposure to maternal stress has not been reported. Objective: We tested whether prenatal and postnatal anxiety and/or depression in pregnant women predicted the risk of their offspring developing asthma in childhood. Methods: The Avon Longitudinal Study of Parents and Children is a population-based birth cohort recruited during pregnancy. Data were available on maternal anxiety scores and asthma at age 71/2 years in 5810 children. Anxiety was assessed at 18 and 32 weeks of gestation by using the validated Crown-Crisp Experiential Index. Asthma was defined at age 71/2 years as doctor-diagnosed asthma with current symptoms or treatment in the previous 12 months. Multivariable logistic regression was used to determine the association of prenatal anxiety with asthma (odds ratio; 95% CI). Results: Independent of postnatal anxiety and adjusted for a number of likely confounders, there was a higher likelihood of asthma at age 71/2 years (odds ratio, 1.64; 95% CI, 1.25-2.17) in children of mothers in the highest compared with lowest quartile of anxiety scores at 32 weeks of gestation, with evidence for a dose-response (P value for trend <0.001). Conclusions: Maternal anxiety symptoms as an indicator of stress during fetal life may program the development of asthma during childhood. (J Allergy Clin Immunol 2009;123:847-853.). anxiety| pregnancy| prenatal programming| asthma| child|day-care attendance| maternal antenatal anxiety| postnatal depression| comorbid anxiety| increased risk| birth-cohort| early-life| stress| disorders| childhood.	APR-2009	anxiety| pregnancy| prenatal programming| asthma| child|day-care attendance| maternal antenatal anxiety| postnatal depression| comorbid anxiety| increased risk| birth-cohort| early-life| stress| disorders| childhood	Cookson, H; Granell, R; Joinson, C; Ben-Shlomo, Y; Henderson, AJ	Mothers' anxiety during pregnancy is associated with asthma in their children		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Anxiety; pregnancy; prenatal programming; asthma; child	DAY-CARE ATTENDANCE; MATERNAL ANTENATAL ANXIETY; POSTNATAL DEPRESSION; COMORBID ANXIETY; INCREASED RISK; BIRTH-COHORT; EARLY-LIFE; STRESS; DISORDERS; CHILDHOOD	Background: Maternal stress in early life has been associated with the development of asthma in children, although it is unclear whether there are any critical periods of exposure. The association of asthma with prenatal exposure to maternal stress has not been reported. Objective: We tested whether prenatal and postnatal anxiety and/or depression in pregnant women predicted the risk of their offspring developing asthma in childhood. Methods: The Avon Longitudinal Study of Parents and Children is a population-based birth cohort recruited during pregnancy. Data were available on maternal anxiety scores and asthma at age 71/2 years in 5810 children. Anxiety was assessed at 18 and 32 weeks of gestation by using the validated Crown-Crisp Experiential Index. Asthma was defined at age 71/2 years as doctor-diagnosed asthma with current symptoms or treatment in the previous 12 months. Multivariable logistic regression was used to determine the association of prenatal anxiety with asthma (odds ratio; 95% CI). Results: Independent of postnatal anxiety and adjusted for a number of likely confounders, there was a higher likelihood of asthma at age 71/2 years (odds ratio, 1.64; 95% CI, 1.25-2.17) in children of mothers in the highest compared with lowest quartile of anxiety scores at 32 weeks of gestation, with evidence for a dose-response (P value for trend <0.001). Conclusions: Maternal anxiety symptoms as an indicator of stress during fetal life may program the development of asthma during childhood. (J Allergy Clin Immunol 2009;123:847-853.)	40	113	2009	7	10.1016/j.jaci.2009.01.042	Allergy; Immunology
"Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease. Background: Airflow limitation in chronic obstructive pulmonary disease ( COPD) is caused by a mixture of small airway disease and emphysema, the relative contributions of which may vary among patients. Phenotypes of COPD classified purely based on severity of emphysema are not well defined and may be different from the classic phenotypes of ""pink puffers'' and ""blue bloaters''. Methods: To characterise clinical phenotypes based on severity of emphysema, 274 subjects with COPD were recruited, excluding those with physician-diagnosed bronchial asthma. For all subjects a detailed interview of disease history and symptoms, quality of life (QOL) measurement, blood sampling, pulmonary function tests before and after inhalation of salbutamol (0.4 mg) and high- resolution CT scanning were performed. Results: Severity of emphysema visually evaluated varied widely even among subjects with the same stage of disease. No significant differences were noted among three groups of subjects classified by severity of emphysema in age, smoking history, chronic bronchitis symptoms, blood eosinophil count, serum IgE level or bronchodilator response. However, subjects with severe emphysema had significantly lower body mass index (BMI) and poorer QOL scores, evaluated using St George's Respiratory Questionnaire (SGRQ), than those with no/mild emphysema (mean ( SD) BMI 21.2 (0.5) vs 23.5 (0.3) kg/m(2), respectively; SGRQ total score 40 (3) vs 28 (2), respectively; p < 0.001 for both). These characteristics held true even if subjects with the same degree of airflow limitation were chosen. Conclusions: The severity of emphysema varies widely even in patients with the same stage of COPD, and chronic bronchitis symptoms are equally distributed irrespective of emphysema severity. Patients with the phenotype in which emphysema predominates have lower BMI and poorer health-related QOL.. air-flow limitation| bronchoalveolar lavage fluid| bronchodilator response| subclinical emphysema| small airways| body-weight| copd| health| mortality| capacity."	NOV-2007	air-flow limitation| bronchoalveolar lavage fluid| bronchodilator response| subclinical emphysema| small airways| body-weight| copd| health| mortality| capacity	Makita, H; Nasuhara, Y; Nagai, K; Ito, Y; Hasegawa, M; Betsuyaku, T; Onodera, Y; Hizawa, N; Nishimura, M	Characterisation of phenotypes based on severity of emphysema in chronic obstructive pulmonary disease		THORAX		AIR-FLOW LIMITATION; BRONCHOALVEOLAR LAVAGE FLUID; BRONCHODILATOR RESPONSE; SUBCLINICAL EMPHYSEMA; SMALL AIRWAYS; BODY-WEIGHT; COPD; HEALTH; MORTALITY; CAPACITY	"Background: Airflow limitation in chronic obstructive pulmonary disease ( COPD) is caused by a mixture of small airway disease and emphysema, the relative contributions of which may vary among patients. Phenotypes of COPD classified purely based on severity of emphysema are not well defined and may be different from the classic phenotypes of ""pink puffers'' and ""blue bloaters''. Methods: To characterise clinical phenotypes based on severity of emphysema, 274 subjects with COPD were recruited, excluding those with physician-diagnosed bronchial asthma. For all subjects a detailed interview of disease history and symptoms, quality of life (QOL) measurement, blood sampling, pulmonary function tests before and after inhalation of salbutamol (0.4 mg) and high- resolution CT scanning were performed. Results: Severity of emphysema visually evaluated varied widely even among subjects with the same stage of disease. No significant differences were noted among three groups of subjects classified by severity of emphysema in age, smoking history, chronic bronchitis symptoms, blood eosinophil count, serum IgE level or bronchodilator response. However, subjects with severe emphysema had significantly lower body mass index (BMI) and poorer QOL scores, evaluated using St George's Respiratory Questionnaire (SGRQ), than those with no/mild emphysema (mean ( SD) BMI 21.2 (0.5) vs 23.5 (0.3) kg/m(2), respectively; SGRQ total score 40 (3) vs 28 (2), respectively; p < 0.001 for both). These characteristics held true even if subjects with the same degree of airflow limitation were chosen. Conclusions: The severity of emphysema varies widely even in patients with the same stage of COPD, and chronic bronchitis symptoms are equally distributed irrespective of emphysema severity. Patients with the phenotype in which emphysema predominates have lower BMI and poorer health-related QOL."	37	113	2007	6	10.1136/thx.2006.072777	Respiratory System
SPDEF regulates goblet cell hyperplasia in the airway epithelium. Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo.. transcription factor-i| surfactant protein-c| sp-a gene| respiratory epithelium| mouse lung| transgenic mice| ets-domain| expression| differentiation| factor-1.	APR-2007	transcription factor-i| surfactant protein-c| sp-a gene| respiratory epithelium| mouse lung| transgenic mice| ets-domain| expression| differentiation| factor-1	Park, KS; Korfhagen, TR; Bruno, MD; Kitzmiller, JA; Wan, HJ; Wert, SE; Hershey, GKK; Chen, G; Whitsett, JA	SPDEF regulates goblet cell hyperplasia in the airway epithelium		JOURNAL OF CLINICAL INVESTIGATION		TRANSCRIPTION FACTOR-I; SURFACTANT PROTEIN-C; SP-A GENE; RESPIRATORY EPITHELIUM; MOUSE LUNG; TRANSGENIC MICE; ETS-DOMAIN; EXPRESSION; DIFFERENTIATION; FACTOR-1	Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo.	47	113	2007	11	10.1172/JCI29176	Research & Experimental Medicine
Stress and atopic disorders. Evidence linking psychological stress to the expression of asthma and atopy continues to grow. Examining the underlying molecular mechanisms linking stress to asthma and other allergic phenomena is an active area of research. Evidence is reviewed for the influence of stress on neuroimmunoregulation and oxidative stress pathways, which, in turn, may affect biological hypersensitivity to environmental stimuli characteristic of atopic disorders. Critical periods of development, including in utero environment, are underscored. The role of genetics and gene-by-environment interactions is also discussed.. asthma| atopy| psychological stress| oxidative stress| psychoneuroimmunology| genetics|psychosocial stress| genetic-variation| maternal stress| birth-cohort| exposure| disease| infancy| asthma| model| psychoneuroimmunology.	DEC-2005	asthma| atopy| psychological stress| oxidative stress| psychoneuroimmunology| genetics|psychosocial stress| genetic-variation| maternal stress| birth-cohort| exposure| disease| infancy| asthma| model| psychoneuroimmunology	Wright, RJ	Stress and atopic disorders		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; atopy; psychological stress; oxidative stress; psychoneuroimmunology; genetics	PSYCHOSOCIAL STRESS; GENETIC-VARIATION; MATERNAL STRESS; BIRTH-COHORT; EXPOSURE; DISEASE; INFANCY; ASTHMA; MODEL; PSYCHONEUROIMMUNOLOGY	Evidence linking psychological stress to the expression of asthma and atopy continues to grow. Examining the underlying molecular mechanisms linking stress to asthma and other allergic phenomena is an active area of research. Evidence is reviewed for the influence of stress on neuroimmunoregulation and oxidative stress pathways, which, in turn, may affect biological hypersensitivity to environmental stimuli characteristic of atopic disorders. Critical periods of development, including in utero environment, are underscored. The role of genetics and gene-by-environment interactions is also discussed.	48	113	2005	6	10.1016/j.jaci.2005.09.050	Allergy; Immunology
Longitudinal study on the relationship between cat allergen and endotoxin exposure, sensitization, cat-specific IgG and development of asthma in childhood - report of the German Multicentre Allergy Study (MAS 90). Background: Controversial data have emerged regarding the question whether cat exposure in childhood favours or decreases the risk of sensitization and allergic airway disease. In a prospective birth-cohort study, we assessed the association between longitudinal cat allergen exposure, sensitization (immunoglobulin E, IgE), IgG antibody (ab) levels to cat and the development of asthma in children up to the age of 10 years. Methods: Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 10 years were available for 750 children. Assessments included yearly measurements of specific serum IgE to cat and at age 6 and 18 months, 3, 4 and 10 years measurement of cat allergen Fel d 1 in house dust samples. Additionally, Fel d 1-specific IgG ab were determined in 378 serum samples of 207 children. Endotoxin exposure in mattress dust was measured in a subgroup of 153 children at age 10 years. From age 4 years on, International Study of Asthma and Allergy in Childhood (ISAAC) questionnaires were completed yearly in order to assess the prevalence of wheeze and asthma. Results: Serum IgG-levels to cat showed a large variation, however, intraindividually values showed rather constant concentration over a longer time period. The IgG levels at school-age correlated with cat allergen exposure during the first 2 years of life. Specific IgE to cat was clearly associated with wheeze ever, current wheeze and bronchial hyperresponsiveness (BHR), this was also observed for children with specific IgE ab to cat (&GT; 0.35 kU/l) plus IgG levels above 125 U/ml. A large percentage of very highly exposed children showed high IgG but no IgE responses to cat, however, not all highly exposed children were found to be protected from sensitization. Children with IgG but without IgE ab to cat showed the lowest prevalence of wheeze ever and current wheeze despite high cat allergen exposure, however, this trend did not achieve significance. While homes of cat owners showed higher Fel d 1 concentrations than homes without cats, homes of cat owners were not found to have higher endotoxin levels in carpet dust samples than homes without cats. Conclusions: We could confirm that high cat allergen exposure in a cohort with lower community prevalence of cats is associated with higher serum IgG and IgE levels to cat in schoolchildren. Sensitization to cat allergen (IgE) is a risk factor for childhood asthma. While exposure to cat allergen during infancy is associated with sensitization (IgE), only in the very highly exposed children the likelihood of sensitization (IgE) is decreased and high IgG levels to cat without IgE were associated with low risk of wheeze. However, cat-specific IgG ab levels did not protect children with IgE-mediated sensitization from wheeze.. cat allergen exposure| childhood asthma| sensitization and immunoglobulin g antibodies to cat|modified th2 response| house-dust| atopic sensitization| pet ownership| birth cohort| early-life| hay-fever| children| risk| disorders.	JUN-2005	cat allergen exposure| childhood asthma| sensitization and immunoglobulin g antibodies to cat|modified th2 response| house-dust| atopic sensitization| pet ownership| birth cohort| early-life| hay-fever| children| risk| disorders	Lau, S; Illi, S; Platts-Mills, TAE; Riposo, D; Nickel, R; Gruber, C; Niggemann, B; Wahn, U	Longitudinal study on the relationship between cat allergen and endotoxin exposure, sensitization, cat-specific IgG and development of asthma in childhood - report of the German Multicentre Allergy Study (MAS 90)		ALLERGY	cat allergen exposure; childhood asthma; sensitization and immunoglobulin G antibodies to cat	MODIFIED TH2 RESPONSE; HOUSE-DUST; ATOPIC SENSITIZATION; PET OWNERSHIP; BIRTH COHORT; EARLY-LIFE; HAY-FEVER; CHILDREN; RISK; DISORDERS	Background: Controversial data have emerged regarding the question whether cat exposure in childhood favours or decreases the risk of sensitization and allergic airway disease. In a prospective birth-cohort study, we assessed the association between longitudinal cat allergen exposure, sensitization (immunoglobulin E, IgE), IgG antibody (ab) levels to cat and the development of asthma in children up to the age of 10 years. Methods: Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 10 years were available for 750 children. Assessments included yearly measurements of specific serum IgE to cat and at age 6 and 18 months, 3, 4 and 10 years measurement of cat allergen Fel d 1 in house dust samples. Additionally, Fel d 1-specific IgG ab were determined in 378 serum samples of 207 children. Endotoxin exposure in mattress dust was measured in a subgroup of 153 children at age 10 years. From age 4 years on, International Study of Asthma and Allergy in Childhood (ISAAC) questionnaires were completed yearly in order to assess the prevalence of wheeze and asthma. Results: Serum IgG-levels to cat showed a large variation, however, intraindividually values showed rather constant concentration over a longer time period. The IgG levels at school-age correlated with cat allergen exposure during the first 2 years of life. Specific IgE to cat was clearly associated with wheeze ever, current wheeze and bronchial hyperresponsiveness (BHR), this was also observed for children with specific IgE ab to cat (&GT; 0.35 kU/l) plus IgG levels above 125 U/ml. A large percentage of very highly exposed children showed high IgG but no IgE responses to cat, however, not all highly exposed children were found to be protected from sensitization. Children with IgG but without IgE ab to cat showed the lowest prevalence of wheeze ever and current wheeze despite high cat allergen exposure, however, this trend did not achieve significance. While homes of cat owners showed higher Fel d 1 concentrations than homes without cats, homes of cat owners were not found to have higher endotoxin levels in carpet dust samples than homes without cats. Conclusions: We could confirm that high cat allergen exposure in a cohort with lower community prevalence of cats is associated with higher serum IgG and IgE levels to cat in schoolchildren. Sensitization to cat allergen (IgE) is a risk factor for childhood asthma. While exposure to cat allergen during infancy is associated with sensitization (IgE), only in the very highly exposed children the likelihood of sensitization (IgE) is decreased and high IgG levels to cat without IgE were associated with low risk of wheeze. However, cat-specific IgG ab levels did not protect children with IgE-mediated sensitization from wheeze.	38	113	2005	8	10.1111/j.1398-9995.2005.00781.x	Allergy; Immunology
Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization. Food allergies are an important cause of life-threatening hypersensitivity reactions. Oral tolerance can be considered the default immune response to dietary antigens, with immune deviation resulting in allergic sensitization. However, primary sensitization to food allergens may not solely be through the gastrointestinal mucosa, as strong T-helper type 2 (Th2)-biased immunity can result from exposure to protein allergens on barrier-disrupted skin. The purpose of this study was to examine whether exposure to allergens through the skin may interfere with the normal development of oral tolerance and promote allergic sensitization to food proteins. Female BALB/c mice were exposed epicutaneously to peanut protein and induction of systemic oral tolerance through high dose feeds of peanut protein was subsequently assessed. Other mice were rendered tolerant prior to epicutaneous peanut exposure. Sensitivity to peanut was determined by assessing delayed-type hypersensitivity, proliferative, cytokine and antibody responses. Epicutaneous exposure to peanut protein induced potent Th2-type immunity with high levels of IL-4 and serum IgE. Primary skin exposure prevented the subsequent induction of oral tolerance to peanut in an antigen-specific manner. Upon oral challenge, mice became further sensitized and developed strong peanut-specific IL-4 and IgE responses. Furthermore, animals with existing tolerance to peanut were partly sensitized following epicutaneous exposure. Epicutaneous exposure to peanut protein can prevent induction of oral tolerance, and may even modify existing tolerance to peanut. Epidermal exposure to protein allergens selectively drives Th2-type responses, and as such may promote sensitization to food proteins upon gastrointestinal exposure.. epicutaneous sensitization| food allergy| ige| oral tolerance| peanut| skin|food allergy| atopic-dermatitis| th2 responses| murine model| prevalence| antigen| immunization| mechanisms| children| diseases.	JUN-2005	epicutaneous sensitization| food allergy| ige| oral tolerance| peanut| skin|food allergy| atopic-dermatitis| th2 responses| murine model| prevalence| antigen| immunization| mechanisms| children| diseases	Strid, J; Hourihane, J; Kimber, I; Callard, R; Strobel, S	Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization		CLINICAL AND EXPERIMENTAL ALLERGY	epicutaneous sensitization; food allergy; IgE; oral tolerance; peanut; skin	FOOD ALLERGY; ATOPIC-DERMATITIS; TH2 RESPONSES; MURINE MODEL; PREVALENCE; ANTIGEN; IMMUNIZATION; MECHANISMS; CHILDREN; DISEASES	Food allergies are an important cause of life-threatening hypersensitivity reactions. Oral tolerance can be considered the default immune response to dietary antigens, with immune deviation resulting in allergic sensitization. However, primary sensitization to food allergens may not solely be through the gastrointestinal mucosa, as strong T-helper type 2 (Th2)-biased immunity can result from exposure to protein allergens on barrier-disrupted skin. The purpose of this study was to examine whether exposure to allergens through the skin may interfere with the normal development of oral tolerance and promote allergic sensitization to food proteins. Female BALB/c mice were exposed epicutaneously to peanut protein and induction of systemic oral tolerance through high dose feeds of peanut protein was subsequently assessed. Other mice were rendered tolerant prior to epicutaneous peanut exposure. Sensitivity to peanut was determined by assessing delayed-type hypersensitivity, proliferative, cytokine and antibody responses. Epicutaneous exposure to peanut protein induced potent Th2-type immunity with high levels of IL-4 and serum IgE. Primary skin exposure prevented the subsequent induction of oral tolerance to peanut in an antigen-specific manner. Upon oral challenge, mice became further sensitized and developed strong peanut-specific IL-4 and IgE responses. Furthermore, animals with existing tolerance to peanut were partly sensitized following epicutaneous exposure. Epicutaneous exposure to peanut protein can prevent induction of oral tolerance, and may even modify existing tolerance to peanut. Epidermal exposure to protein allergens selectively drives Th2-type responses, and as such may promote sensitization to food proteins upon gastrointestinal exposure.	36	113	2005	10	10.1111/j.1365-2222.2005.02260.x	Allergy; Immunology
Putting copper into action: copper-impregnated products with potent biocidal activities. Copper ions, either alone or in copper complexes, have been used for centuries to disinfect liquids, solids, and human tissue. Today copper is used as a water purifier, algaecide, fungicide, nematocide, molluscicide, and antibacterial and antifouling agent. Copper also displays potent antiviral activity. We hypothesized that introducing copper into clothing, bedding, and other articles would provide them with biocidal properties. A durable platform technology has been developed that introduces copper into cotton fibers, latex, and other polymeric materials. This study demonstrates the broad-spectrum antimicrobial ( antibacterial, antiviral, antifungal) and antimite activities of copper-impregnated fibers and polyester products. This technology enabled the production of antiviral gloves and filters (which deactivate HIV-1 and other viruses), antibacterial self-sterilizing fabrics (which kill antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci), antifungal socks (which alleviate symptoms of athlete's foot), and anti-dust mite mattress covers (which reduce mite-related allergies). These products did not have skin-sensitizing properties, as determined by guine pig maximization and rabbit skin irritation tests. Our study demonstrates the potential use of copper in new applications. These applications address medical issues of the greatest importance, such as viral transmissions; nosocomial, or healthcare-associated, infections; and the spread of antibiotic-resistant bacteria.. hiv-1| filters| fabrics| dust mites| athlete's foot|metal-ions| intrauterine-devices| blood-transfusion| marathon runners| plasma-membrane| tinea-pedis| virus| inactivation| mechanisms| hiv-1.	SEP-2004	hiv-1| filters| fabrics| dust mites| athlete's foot|metal-ions| intrauterine-devices| blood-transfusion| marathon runners| plasma-membrane| tinea-pedis| virus| inactivation| mechanisms| hiv-1	Borkow, G; Gabbay, J	Putting copper into action: copper-impregnated products with potent biocidal activities		FASEB JOURNAL	HIV-1; filters; fabrics; dust mites; athlete's foot	METAL-IONS; INTRAUTERINE-DEVICES; BLOOD-TRANSFUSION; MARATHON RUNNERS; PLASMA-MEMBRANE; TINEA-PEDIS; VIRUS; INACTIVATION; MECHANISMS; HIV-1	Copper ions, either alone or in copper complexes, have been used for centuries to disinfect liquids, solids, and human tissue. Today copper is used as a water purifier, algaecide, fungicide, nematocide, molluscicide, and antibacterial and antifouling agent. Copper also displays potent antiviral activity. We hypothesized that introducing copper into clothing, bedding, and other articles would provide them with biocidal properties. A durable platform technology has been developed that introduces copper into cotton fibers, latex, and other polymeric materials. This study demonstrates the broad-spectrum antimicrobial ( antibacterial, antiviral, antifungal) and antimite activities of copper-impregnated fibers and polyester products. This technology enabled the production of antiviral gloves and filters (which deactivate HIV-1 and other viruses), antibacterial self-sterilizing fabrics (which kill antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci), antifungal socks (which alleviate symptoms of athlete's foot), and anti-dust mite mattress covers (which reduce mite-related allergies). These products did not have skin-sensitizing properties, as determined by guine pig maximization and rabbit skin irritation tests. Our study demonstrates the potential use of copper in new applications. These applications address medical issues of the greatest importance, such as viral transmissions; nosocomial, or healthcare-associated, infections; and the spread of antibiotic-resistant bacteria.	51	113	2004	19	10.1096/fj.04-2029fje	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology
Disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response. The skin is an important immunological organ with an outer protective layer, the stratum corneum forming a barrier between the skin-associated lymphoid tissue and the environment. We show that gently removing the stratum corneum with adhesive tape permits potent epicutaneous immunization to protein antigens. IL-4 secretion by T cells from draining lymph nodes and high levels of specific IgE and IgG1 with no IgG2a showed that the immune responses induced following epicutaneous antigen exposure are strongly Th2 biased. Similar responses were obtained With different antigens and mouse strains. In contrast, subcutaneous immunization with antigen delivery into the dermis was less potent and gave predominantly Th1 responses. Removal of the stratum corneum increased expression of MHC class II, CD86, CD40, CD54 and CD11c on Langerhans cells, but did not cause them to migrate. Rapid migration from epidermis to draining lymph node was obtained, however, by exposure to antigen after removal of the stratum corneum, suggesting that maturation and migration of Langerhans cells are independently regulated events. These results suggest that antigen presentation by Langerhans cells gives predominantly Th2 responses. This may provide an explanation for allergic sensitization to some antigens. It may also be a useful non-invasive, non-adjuvant-dependent method of vaccination.. skin| th1/th2 cells| allergy| langerhans cells| vaccination|tumor-necrosis-factor| dendritic cells| langerhans cells| peanut allergy| aerosolized antigen| atopic-dermatitis| ige production| food allergy| factor-alpha| bare skin.	AUG-2004	skin| th1/th2 cells| allergy| langerhans cells| vaccination|tumor-necrosis-factor| dendritic cells| langerhans cells| peanut allergy| aerosolized antigen| atopic-dermatitis| ige production| food allergy| factor-alpha| bare skin	Strid, J; Hourihane, J; Kimber, I; Callard, R; Strobel, S	Disruption of the stratum corneum allows potent epicutaneous immunization with protein antigens resulting in a dominant systemic Th2 response		EUROPEAN JOURNAL OF IMMUNOLOGY	skin; Th1/Th2 cells; allergy; Langerhans cells; vaccination	TUMOR-NECROSIS-FACTOR; DENDRITIC CELLS; LANGERHANS CELLS; PEANUT ALLERGY; AEROSOLIZED ANTIGEN; ATOPIC-DERMATITIS; IGE PRODUCTION; FOOD ALLERGY; FACTOR-ALPHA; BARE SKIN	The skin is an important immunological organ with an outer protective layer, the stratum corneum forming a barrier between the skin-associated lymphoid tissue and the environment. We show that gently removing the stratum corneum with adhesive tape permits potent epicutaneous immunization to protein antigens. IL-4 secretion by T cells from draining lymph nodes and high levels of specific IgE and IgG1 with no IgG2a showed that the immune responses induced following epicutaneous antigen exposure are strongly Th2 biased. Similar responses were obtained With different antigens and mouse strains. In contrast, subcutaneous immunization with antigen delivery into the dermis was less potent and gave predominantly Th1 responses. Removal of the stratum corneum increased expression of MHC class II, CD86, CD40, CD54 and CD11c on Langerhans cells, but did not cause them to migrate. Rapid migration from epidermis to draining lymph node was obtained, however, by exposure to antigen after removal of the stratum corneum, suggesting that maturation and migration of Langerhans cells are independently regulated events. These results suggest that antigen presentation by Langerhans cells gives predominantly Th2 responses. This may provide an explanation for allergic sensitization to some antigens. It may also be a useful non-invasive, non-adjuvant-dependent method of vaccination.	42	113	2004	10	10.1002/eji.200324843	Immunology
Blockade of inflammation and airway hyperresponsiveness in immune-sensitized mice by dominant-negative phosphoinositide 3-kinase-TAT. Phosphoinositide 3-kinase (PI3K) is thought to contribute to the pathogenesis of asthma by effecting the recruitment, activation, and apoptosis of inflammatory cells. We examined the role of class IA PI3K in antigen-induced air-way inflammation and hyperresponsiveness by i.p. administration into mice of Deltap85 protein, a dominant negative form of the class IA PI3K regulatory subunit, p85alpha, which was fused to HIV-TAT (TAT-Deltap85). Intraperitoneal administration of TXT-Deltap85 caused time-dependent transduction into blood leukocytes, and inhibited activated phosphorylation of protein kinase B (PKB), a downstream target of PI3K, in lung tissues in mice receiving intranasal FMLP. Antigen challenge elicited pulmonary infiltration of lymphocytes, eosinophils and neutrophils, increase in mucus-containing epithelial cells, and airway hyperresponsiveness to methacholine. Except for modest airway neutrophilia, these effects all were blocked by treatment with 3-10 mg/kg of TAT-Deltap85. There was also significant reduction in IL-5 and IL-4 secretion into the BAL. Intranasal administration of IL-5 caused eosinophil migration into the air-way lumen, which was attenuated by systemic pretreatment with TAT-Deltap85. We conclude that PI3K has a regulatory role in Th2-cell cytokine secretion, airway inflammation, and air-way hyperresponsiveness in mice.. allergy| cytokines| eosinophils| lung| inflammation|fc-epsilon-ri| in-vivo| human eosinophils| phosphatidylinositol 3-kinase| bronchial responsiveness| gene-expression| guinea-pigs| mast-cells| b-cells| asthma.	NOV 17-2003	allergy| cytokines| eosinophils| lung| inflammation|fc-epsilon-ri| in-vivo| human eosinophils| phosphatidylinositol 3-kinase| bronchial responsiveness| gene-expression| guinea-pigs| mast-cells| b-cells| asthma	Myou, S; Leff, AR; Myo, S; Boetticher, E; Tong, JK; Meliton, AY; Liu, J; Munoz, NM; Zhu, XD	Blockade of inflammation and airway hyperresponsiveness in immune-sensitized mice by dominant-negative phosphoinositide 3-kinase-TAT		JOURNAL OF EXPERIMENTAL MEDICINE	allergy; cytokines; eosinophils; lung; inflammation	FC-EPSILON-RI; IN-VIVO; HUMAN EOSINOPHILS; PHOSPHATIDYLINOSITOL 3-KINASE; BRONCHIAL RESPONSIVENESS; GENE-EXPRESSION; GUINEA-PIGS; MAST-CELLS; B-CELLS; ASTHMA	Phosphoinositide 3-kinase (PI3K) is thought to contribute to the pathogenesis of asthma by effecting the recruitment, activation, and apoptosis of inflammatory cells. We examined the role of class IA PI3K in antigen-induced air-way inflammation and hyperresponsiveness by i.p. administration into mice of Deltap85 protein, a dominant negative form of the class IA PI3K regulatory subunit, p85alpha, which was fused to HIV-TAT (TAT-Deltap85). Intraperitoneal administration of TXT-Deltap85 caused time-dependent transduction into blood leukocytes, and inhibited activated phosphorylation of protein kinase B (PKB), a downstream target of PI3K, in lung tissues in mice receiving intranasal FMLP. Antigen challenge elicited pulmonary infiltration of lymphocytes, eosinophils and neutrophils, increase in mucus-containing epithelial cells, and airway hyperresponsiveness to methacholine. Except for modest airway neutrophilia, these effects all were blocked by treatment with 3-10 mg/kg of TAT-Deltap85. There was also significant reduction in IL-5 and IL-4 secretion into the BAL. Intranasal administration of IL-5 caused eosinophil migration into the air-way lumen, which was attenuated by systemic pretreatment with TAT-Deltap85. We conclude that PI3K has a regulatory role in Th2-cell cytokine secretion, airway inflammation, and air-way hyperresponsiveness in mice.	51	113	2003	10	10.1084/jem.20030298	Immunology; Research & Experimental Medicine
Psychological aspects of asthma. Asthma can be affected by stress, anxiety, sadness, and suggestion, as well as by environmental irritants or allergens, exercise, and infection. It also is associated with an elevated prevalence of anxiety and depressive disorders. Asthma and these psychological states and traits may mutually potentiate each other through direct psychophysiological mediation, nonadherence to medical regimen, exposure to asthma triggers, and inaccuracy of asthma symptom perception. Defensiveness is associated with inaccurate perception of airway resistance and stress-related bronchoconstriction. Asthma education programs that teach about the nature of the disease, medications, and trigger avoidance tend to reduce asthma morbidity. Other promising psychological interventions as adjuncts to medical treatment include training in symptom perception, stress management, hypnosis, yoga, and several biofeedback procedures.. peak expiratory flow| near-fatal asthma| self-management program| respiratory sinus arrhythmia| inspiratory resistive loads| life-threatening asthma| vocal cord dysfunction| inner-city children| randomized controlled-trial| health belief model.	JUN-2002	peak expiratory flow| near-fatal asthma| self-management program| respiratory sinus arrhythmia| inspiratory resistive loads| life-threatening asthma| vocal cord dysfunction| inner-city children| randomized controlled-trial| health belief model	Lehrer, P; Feldman, J; Giardino, N; Song, HS; Schmaling, K	Psychological aspects of asthma		JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY		PEAK EXPIRATORY FLOW; NEAR-FATAL ASTHMA; SELF-MANAGEMENT PROGRAM; RESPIRATORY SINUS ARRHYTHMIA; INSPIRATORY RESISTIVE LOADS; LIFE-THREATENING ASTHMA; VOCAL CORD DYSFUNCTION; INNER-CITY CHILDREN; RANDOMIZED CONTROLLED-TRIAL; HEALTH BELIEF MODEL	Asthma can be affected by stress, anxiety, sadness, and suggestion, as well as by environmental irritants or allergens, exercise, and infection. It also is associated with an elevated prevalence of anxiety and depressive disorders. Asthma and these psychological states and traits may mutually potentiate each other through direct psychophysiological mediation, nonadherence to medical regimen, exposure to asthma triggers, and inaccuracy of asthma symptom perception. Defensiveness is associated with inaccurate perception of airway resistance and stress-related bronchoconstriction. Asthma education programs that teach about the nature of the disease, medications, and trigger avoidance tend to reduce asthma morbidity. Other promising psychological interventions as adjuncts to medical treatment include training in symptom perception, stress management, hypnosis, yoga, and several biofeedback procedures.	279	113	2002	21	10.1037//0022-006X.70.3.691	Psychology
Clinical importance of Alternaria exposure in children. The fungus Alternaria is known to be allergenic and is one of the most common fungi worldwide. We investigated the extent to which exposure to Alternaria increases the severity of asthma. We undertook a prospective cohort study in Australia of 399 school children who had positive skin tests to one or more aeroallergens. Airway responsiveness to histamine, wheeze, and bronchodilator use in 1 mo was measured five times between 1997 and 1999. Airway hyperresponsiveness was defined as PD20FEV1 = 3.9 mu mol histamine. Airborne concentrations of Alternaria spores were measured throughout the study, and mean daily concentrations over 1 mo ranged from 2.2 to 307.7 spores/m(3) of ambient air. Using generalized estimating equations, we found that airway responsiveness, wheeze, and bronchodilator use increased significantly in association with increased spore concentrations and that the increase in airway responsiveness was greater in children sensitized to Alternarxia than in other children (p = 0.01). The odds ratio for airway hyperresponsiveness in children sensitized to Alternaria was 1.26 (95% CI, 1.14 to 1.39) after an increase in mean exposure of 100 spore/m(3)/d over 1 mo. These results suggest that Alternaria allergens contribute to severe asthma in regions where exposure to the fungus is high.. alternaria| airway responsiveness| asthma| fungi| children|bronchial responsiveness| allergic sensitization| longitudinal data| childhood asthma| climatic regions| alt-i| population| severity| outdoor| spore.	AUG 1-2001	alternaria| airway responsiveness| asthma| fungi| children|bronchial responsiveness| allergic sensitization| longitudinal data| childhood asthma| climatic regions| alt-i| population| severity| outdoor| spore	Downs, SH; Mitakakis, TZ; Marks, GB; Car, NG; Belousova, EG; Leuppi, JD; Xuan, W; Downie, SR; Tobias, A; Peat, JK	Clinical importance of Alternaria exposure in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	Alternaria; airway responsiveness; asthma; fungi; children	BRONCHIAL RESPONSIVENESS; ALLERGIC SENSITIZATION; LONGITUDINAL DATA; CHILDHOOD ASTHMA; CLIMATIC REGIONS; ALT-I; POPULATION; SEVERITY; OUTDOOR; SPORE	The fungus Alternaria is known to be allergenic and is one of the most common fungi worldwide. We investigated the extent to which exposure to Alternaria increases the severity of asthma. We undertook a prospective cohort study in Australia of 399 school children who had positive skin tests to one or more aeroallergens. Airway responsiveness to histamine, wheeze, and bronchodilator use in 1 mo was measured five times between 1997 and 1999. Airway hyperresponsiveness was defined as PD20FEV1 = 3.9 mu mol histamine. Airborne concentrations of Alternaria spores were measured throughout the study, and mean daily concentrations over 1 mo ranged from 2.2 to 307.7 spores/m(3) of ambient air. Using generalized estimating equations, we found that airway responsiveness, wheeze, and bronchodilator use increased significantly in association with increased spore concentrations and that the increase in airway responsiveness was greater in children sensitized to Alternarxia than in other children (p = 0.01). The odds ratio for airway hyperresponsiveness in children sensitized to Alternaria was 1.26 (95% CI, 1.14 to 1.39) after an increase in mean exposure of 100 spore/m(3)/d over 1 mo. These results suggest that Alternaria allergens contribute to severe asthma in regions where exposure to the fungus is high.	42	113	2001	5		General & Internal Medicine; Respiratory System
The production of extracellular matrix proteins by human passively sensitized airway smooth-muscle cells in culture - The effect of beclomethasone. Airway remodeling is a key feature of persistent asthma. Part of the remodeling process involves the laying down of extracellular matrix (ECM) proteins within the airways. In this study we compared the production of ECM proteins by human airway smooth-muscle (ASM) cells in culture after exposure to 10% serum from an asthmatic individual or 10% serum from a nonasthmatic individual with or without beclomethasone (0.01 to 100 nM). Enzyme-linked immunosorbent assays were done with antibodies to human fibronectin; perlecan; elastin; the laminin beta (1), gamma (1), beta (2), alpha (1), chains; thrombospondin; chondroitin sulfate; collagen types I, III, IV, and V; versican; and decorin. Serum from the asthmatic individual, when compared with that from the nonasthmatic individual, caused a significant increase in the production of fibronectin, perlecan, laminin gamma (1), and chondroitin sulfate. Beclomethasone caused a significant reduction in the number of cells exposed to serum from either the asthmatic or nonasthmatic individual, but did not reverse the increase in ECM protein induced by the former. These results suggest an interaction between the ASM and the allergic process that may alter components of the airway wall in asthma, and that corticosteroids may not prevent the fibrosis induced by resident cells within the airways.. subepithelial fibrosis| altered responsiveness| fibronectin expression| bronchial-asthma| adhesion| proliferation| dexamethasone| antibodies| inhibition| collagen.	DEC-2000	subepithelial fibrosis| altered responsiveness| fibronectin expression| bronchial-asthma| adhesion| proliferation| dexamethasone| antibodies| inhibition| collagen	Johnson, PRA; Black, JL; Carlin, S; Ge, Q; Underwood, PA	The production of extracellular matrix proteins by human passively sensitized airway smooth-muscle cells in culture - The effect of beclomethasone		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		SUBEPITHELIAL FIBROSIS; ALTERED RESPONSIVENESS; FIBRONECTIN EXPRESSION; BRONCHIAL-ASTHMA; ADHESION; PROLIFERATION; DEXAMETHASONE; ANTIBODIES; INHIBITION; COLLAGEN	Airway remodeling is a key feature of persistent asthma. Part of the remodeling process involves the laying down of extracellular matrix (ECM) proteins within the airways. In this study we compared the production of ECM proteins by human airway smooth-muscle (ASM) cells in culture after exposure to 10% serum from an asthmatic individual or 10% serum from a nonasthmatic individual with or without beclomethasone (0.01 to 100 nM). Enzyme-linked immunosorbent assays were done with antibodies to human fibronectin; perlecan; elastin; the laminin beta (1), gamma (1), beta (2), alpha (1), chains; thrombospondin; chondroitin sulfate; collagen types I, III, IV, and V; versican; and decorin. Serum from the asthmatic individual, when compared with that from the nonasthmatic individual, caused a significant increase in the production of fibronectin, perlecan, laminin gamma (1), and chondroitin sulfate. Beclomethasone caused a significant reduction in the number of cells exposed to serum from either the asthmatic or nonasthmatic individual, but did not reverse the increase in ECM protein induced by the former. These results suggest an interaction between the ASM and the allergic process that may alter components of the airway wall in asthma, and that corticosteroids may not prevent the fibrosis induced by resident cells within the airways.	37	113	2000	7		General & Internal Medicine; Respiratory System
YKL-40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages. YKL-40 is a chitin-binding protein that is elevated in patients with various inflammatory conditions associated with ongoing remodeling. We investigated whether the levels of YKL-40 were up-regulated in the circulation and the airways of patients with chronic obstructive pulmonary disease (COPD), and whether it promoted the production of inflammatory mediators from macrophages. Serum, bronchoalveolar lavage (BAL), bronchial biopsies, lung tissue specimens, and alveolar macrophages from never-smokers (n = 15), smokers without COPD (n = 20), and smokers with COPD (n = 30) were assessed for YKL-40 levels and immunolocalization. In addition, YKL-40-induced mediator release from alveolar macrophages was examined. We found that smokers with COPD had elevated levels of YKL-40 in serum (p <= 0.027) and BAL (p <= 0.007), more YKL-40-positive cells in bronchial biopsies (p <= 0.03), and a greater proportion of alveolar macrophages expressing YKL-40 than smokers without COPD or never-smokers. YKL-40 levels in serum and BAL were associated with airflow obstruction (pre-beta(2) agonist forced expiratory volume in 1 s, r(s) = -0.3892,p = 0.0072 and r(s) = -0.5491, p < 0.0001, respectively) and impaired diffusion lung capacity (transfer factor of the lung for carbon monoxide, r(s) = -0.4667, p = 0.002 and r(s) = -0.3854, p = 0.0045, respectively). TNF-alpha stimulated YKL-40 synthesis in alveolar macrophages from smokers with COPD, and exposure of these cells to YKL-40 promoted the release of IL-8, MCP-1, MIP-1 alpha, and metalloproteinase-9. We conclude that YKL-40 is up-regulated in COPD, in which it may contribute to tissue inflammation and remodeling by sustaining the synthesis of proinflammatory and fibrogenic chemokines and of metalloproteinases by alveolar macrophages.. serum ykl-40| stimulates proliferation| chitinase family| severe asthma| protein| lung| inflammation| collagen| hc-gp39| differentiation.	OCT 1-2008	serum ykl-40| stimulates proliferation| chitinase family| severe asthma| protein| lung| inflammation| collagen| hc-gp39| differentiation	Letuve, S; Kozhich, A; Arouche, N; Grandsaigne, M; Reed, J; Dombret, MC; Kiener, PA; Aubier, M; Coyle, AJ; Pretolani, M	YKL-40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages		JOURNAL OF IMMUNOLOGY		SERUM YKL-40; STIMULATES PROLIFERATION; CHITINASE FAMILY; SEVERE ASTHMA; PROTEIN; LUNG; INFLAMMATION; COLLAGEN; HC-GP39; DIFFERENTIATION	YKL-40 is a chitin-binding protein that is elevated in patients with various inflammatory conditions associated with ongoing remodeling. We investigated whether the levels of YKL-40 were up-regulated in the circulation and the airways of patients with chronic obstructive pulmonary disease (COPD), and whether it promoted the production of inflammatory mediators from macrophages. Serum, bronchoalveolar lavage (BAL), bronchial biopsies, lung tissue specimens, and alveolar macrophages from never-smokers (n = 15), smokers without COPD (n = 20), and smokers with COPD (n = 30) were assessed for YKL-40 levels and immunolocalization. In addition, YKL-40-induced mediator release from alveolar macrophages was examined. We found that smokers with COPD had elevated levels of YKL-40 in serum (p <= 0.027) and BAL (p <= 0.007), more YKL-40-positive cells in bronchial biopsies (p <= 0.03), and a greater proportion of alveolar macrophages expressing YKL-40 than smokers without COPD or never-smokers. YKL-40 levels in serum and BAL were associated with airflow obstruction (pre-beta(2) agonist forced expiratory volume in 1 s, r(s) = -0.3892,p = 0.0072 and r(s) = -0.5491, p < 0.0001, respectively) and impaired diffusion lung capacity (transfer factor of the lung for carbon monoxide, r(s) = -0.4667, p = 0.002 and r(s) = -0.3854, p = 0.0045, respectively). TNF-alpha stimulated YKL-40 synthesis in alveolar macrophages from smokers with COPD, and exposure of these cells to YKL-40 promoted the release of IL-8, MCP-1, MIP-1 alpha, and metalloproteinase-9. We conclude that YKL-40 is up-regulated in COPD, in which it may contribute to tissue inflammation and remodeling by sustaining the synthesis of proinflammatory and fibrogenic chemokines and of metalloproteinases by alveolar macrophages.	33	112	2008	7	10.4049/jimmunol.181.7.5167	Immunology
Urban air pollution, and asthma and COPD hospital emergency room visits. Background: There is little previous information of the effects of size fractioned particulate air pollution and source specific fine particles (PM(2.5); <2.5 mu m) on asthma and chronic obstructive pulmonary disease (COPD) among children, adults and the elderly. Objectives: To determine the effects of daily variation in levels of different particle size fractions and gaseous pollutants on asthma and COPD by age group. Methods: Levels of particulate air pollution, NO(2) and CO were measured from 1998 to 2004 at central outdoor monitoring sites in Helsinki, Finland. Associations between daily pollution levels and hospital emergency room visits were evaluated for asthma (ICD10: J45+J46) in children,15 years old, and for asthma and COPD (ICD10: J41+J44) in adults (15-64 years) and the elderly (>= 65 years). Results: Three to 5 day lagged increases in asthma visits were found among children in association with nucleation (<0.03 mu m), Aitken (0.03-0.1 mu m) and accumulation (0.1-0.29 mu m) mode particles, gaseous pollutants and traffic related PM(2.5) (7.8% (95% CI 3.5 to 12.3) for 1.1 mu g/m(3) increase in traffic related PM(2.5) at lag 4). Pooled asthma-COPD visits among the elderly were associated with lag 0 of PM(2.5), coarse particles, gaseous pollutants and long range transported and traffic related PM(2.5) (3.9% (95% CI 0.28 to 7.7) at lag 0). Only accumulation mode and coarse particles were associated with asthma and COPD among adults. Conclusions: Among children, traffic related PM(2.5) had delayed effects, whereas among the elderly, several types of particles had effects that were more immediate. These findings suggest that the mechanisms of the respiratory effects of air pollution, and responsible pollutants, differ by age group.. ultrafine particles| particulate matter| short-term| number| health| admissions| inflammation| pollutants| exposure| disease.	JUL-2008	ultrafine particles| particulate matter| short-term| number| health| admissions| inflammation| pollutants| exposure| disease	Halonen, JI; Lanki, T; Yli-Tuomi, T; Kulmala, M; Tiittanen, P; Pekkanen, J	Urban air pollution, and asthma and COPD hospital emergency room visits		THORAX		ULTRAFINE PARTICLES; PARTICULATE MATTER; SHORT-TERM; NUMBER; HEALTH; ADMISSIONS; INFLAMMATION; POLLUTANTS; EXPOSURE; DISEASE	Background: There is little previous information of the effects of size fractioned particulate air pollution and source specific fine particles (PM(2.5); <2.5 mu m) on asthma and chronic obstructive pulmonary disease (COPD) among children, adults and the elderly. Objectives: To determine the effects of daily variation in levels of different particle size fractions and gaseous pollutants on asthma and COPD by age group. Methods: Levels of particulate air pollution, NO(2) and CO were measured from 1998 to 2004 at central outdoor monitoring sites in Helsinki, Finland. Associations between daily pollution levels and hospital emergency room visits were evaluated for asthma (ICD10: J45+J46) in children,15 years old, and for asthma and COPD (ICD10: J41+J44) in adults (15-64 years) and the elderly (>= 65 years). Results: Three to 5 day lagged increases in asthma visits were found among children in association with nucleation (<0.03 mu m), Aitken (0.03-0.1 mu m) and accumulation (0.1-0.29 mu m) mode particles, gaseous pollutants and traffic related PM(2.5) (7.8% (95% CI 3.5 to 12.3) for 1.1 mu g/m(3) increase in traffic related PM(2.5) at lag 4). Pooled asthma-COPD visits among the elderly were associated with lag 0 of PM(2.5), coarse particles, gaseous pollutants and long range transported and traffic related PM(2.5) (3.9% (95% CI 0.28 to 7.7) at lag 0). Only accumulation mode and coarse particles were associated with asthma and COPD among adults. Conclusions: Among children, traffic related PM(2.5) had delayed effects, whereas among the elderly, several types of particles had effects that were more immediate. These findings suggest that the mechanisms of the respiratory effects of air pollution, and responsible pollutants, differ by age group.	32	112	2008	7	10.1136/thx.2007.091371	Respiratory System
Helminths as governors of immune-mediated inflammation. Immune-mediated diseases (e.g. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes) are increasing in prevalence and emerge as populations adopt meticulously hygienic lifestyles. This change in lifestyles precludes exposure to helminths (parasitic worms). Loss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms. Helminths protect animals from developing immune-mediated diseases (colitis, reactive airway disease, encephalitis and diabetes). Clinical trials show that exposure to helminths can reduce disease activity in patients with ulcerative colitis or Crohn's disease. This paper summarises work by multiple groups demonstrating that colonization with helminths alters immune reactivity and protects against disease from dysregulated inflammation. (c) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.. immune regulation| inflammation| inflammatory bowel disease| asthma| multiple sclerosis| autoimmune type 1 diabetes| immune-mediated inflammatory disease| trichuris suis| whipworm| hookworm|experimental autoimmune encephalomyelitis| trichuris-suis therapy| regulatory t-cells| bowel-disease| necator-americanus| induced colitis| crohns-disease| intestinal parasites| multiple-sclerosis| ulcerative-colitis.	APR-2007	immune regulation| inflammation| inflammatory bowel disease| asthma| multiple sclerosis| autoimmune type 1 diabetes| immune-mediated inflammatory disease| trichuris suis| whipworm| hookworm|experimental autoimmune encephalomyelitis| trichuris-suis therapy| regulatory t-cells| bowel-disease| necator-americanus| induced colitis| crohns-disease| intestinal parasites| multiple-sclerosis| ulcerative-colitis	Elliott, DE; Summers, RW; Weinstock, JV	Helminths as governors of immune-mediated inflammation		INTERNATIONAL JOURNAL FOR PARASITOLOGY	immune regulation; inflammation; inflammatory bowel disease; asthma; multiple sclerosis; autoimmune type 1 diabetes; immune-mediated inflammatory disease; Trichuris suis; whipworm; hookworm	EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TRICHURIS-SUIS THERAPY; REGULATORY T-CELLS; BOWEL-DISEASE; NECATOR-AMERICANUS; INDUCED COLITIS; CROHNS-DISEASE; INTESTINAL PARASITES; MULTIPLE-SCLEROSIS; ULCERATIVE-COLITIS	Immune-mediated diseases (e.g. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes) are increasing in prevalence and emerge as populations adopt meticulously hygienic lifestyles. This change in lifestyles precludes exposure to helminths (parasitic worms). Loss of natural helminth exposure removes a previously universal Th2 and regulatory immune biasing imparted by these organisms. Helminths protect animals from developing immune-mediated diseases (colitis, reactive airway disease, encephalitis and diabetes). Clinical trials show that exposure to helminths can reduce disease activity in patients with ulcerative colitis or Crohn's disease. This paper summarises work by multiple groups demonstrating that colonization with helminths alters immune reactivity and protects against disease from dysregulated inflammation. (c) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.	57	112	2007	8	10.1016/j.ijpara.2006.12.009	Parasitology
Symptom-based questionnaire for identifying COPD in smokers. Background: Symptom-based questionnaires may enhance chronic obstructive pulmonary disease (COPD) screening in primary care. Objectives: We prospectively tested questions to help identify COPD among smokers without prior history of lung disease. Methods: Subjects were recruited via random mailing to primary care practices in Aberdeen, UK, and Denver, Colo., USA. Current and former smokers aged 40 or older with no prior respiratory diagnosis and no respiratory medications in the past year were enrolled. Participants answered questions covering demographics and symptoms and then underwent spirometry with reversibility testing. A study diagnosis of COPD was defined as fixed airway obstruction as measured by postbronchodilator FEV1/FVC <0.70. We examined the ability of individual questions in a multivariate framework to correctly discriminate between persons with and without COPD. Results: 818 subjects completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analysis, which was reduced to 17 items for entry into multivariate regression. Eight items had significant relationships with the study diagnosis of COPD, including age, pack-years, body mass index, weather-affected cough, phlegm without a cold, morning phlegm, wheeze frequency, and history of any allergies. Individual items yielded odds ratios ranging from 0.23 to 12. This questionnaire demonstrated a sensitivity of 80.4 and specificity of 72.0. Conclusions: A simple patient self-administered questionnaire can be used to identify patients with a high likelihood of having COPD, for whom spirometric testing is particularly important. Implementation of this questionnaire could enhance the efficiency and diagnostic accuracy of current screening efforts. Copyright (C) 2006 S. Karger AG, Basel.. chronic obstructive pulmonary disease| diagnosis| primary care| questionnaires| spirometry| validation studies|obstructive pulmonary-disease| air-flow obstruction| general-practice| risk| population| guidelines| diagnosis| smoking| program| asthma.	2006	chronic obstructive pulmonary disease| diagnosis| primary care| questionnaires| spirometry| validation studies|obstructive pulmonary-disease| air-flow obstruction| general-practice| risk| population| guidelines| diagnosis| smoking| program| asthma	Price, DB; Tinkelman, DG; Halbert, RJ; Nordyke, RJ; Isonaka, S; Nonikov, D; Juniper, EF; Freeman, D; Hausen, T; Levy, ML; Ostrem, A; van der Molen, T; van Schayck, CP	Symptom-based questionnaire for identifying COPD in smokers		RESPIRATION	chronic obstructive pulmonary disease; diagnosis; primary care; questionnaires; spirometry; validation studies	OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; GENERAL-PRACTICE; RISK; POPULATION; GUIDELINES; DIAGNOSIS; SMOKING; PROGRAM; ASTHMA	Background: Symptom-based questionnaires may enhance chronic obstructive pulmonary disease (COPD) screening in primary care. Objectives: We prospectively tested questions to help identify COPD among smokers without prior history of lung disease. Methods: Subjects were recruited via random mailing to primary care practices in Aberdeen, UK, and Denver, Colo., USA. Current and former smokers aged 40 or older with no prior respiratory diagnosis and no respiratory medications in the past year were enrolled. Participants answered questions covering demographics and symptoms and then underwent spirometry with reversibility testing. A study diagnosis of COPD was defined as fixed airway obstruction as measured by postbronchodilator FEV1/FVC <0.70. We examined the ability of individual questions in a multivariate framework to correctly discriminate between persons with and without COPD. Results: 818 subjects completed all investigations and proceeded to analysis. The list of 54 questions yielded 52 items for analysis, which was reduced to 17 items for entry into multivariate regression. Eight items had significant relationships with the study diagnosis of COPD, including age, pack-years, body mass index, weather-affected cough, phlegm without a cold, morning phlegm, wheeze frequency, and history of any allergies. Individual items yielded odds ratios ranging from 0.23 to 12. This questionnaire demonstrated a sensitivity of 80.4 and specificity of 72.0. Conclusions: A simple patient self-administered questionnaire can be used to identify patients with a high likelihood of having COPD, for whom spirometric testing is particularly important. Implementation of this questionnaire could enhance the efficiency and diagnostic accuracy of current screening efforts. Copyright (C) 2006 S. Karger AG, Basel.	36	112	2006	11	10.1159/000090142	Respiratory System
Anaphylactic reactions in children - a questionnaire-based survey in Germany. Background: Severe anaphylactic reactions are medical emergencies requiring immediate recognition and treatment. Despite this, little is known on their clinical features, especially in infants and children. Objective: To evaluate trigger factors, patterns of clinical reaction, site of occurrence and treatment modalities of reported reaction in infants and children below 12 years of age in Germany. Methods: Paediatricians throughout Germany were asked by questionnaire to report accidental anaphylactic reactions over the previous 12 months. Severity of reported reactions was classified in grades I-IV according to reported symptoms. Results: Hundred and three cases of anaphylaxis were evaluated. Median age was 5 years, 58% were boys. Site of occurrence was the child's home in the majority of cases (58%). Foods were the most common causative allergen (57%), followed by insect stings (13%) and immunotherapy (SIT) (12%); in 8% anaphylactic agent was unknown. Among foods, peanuts and tree nuts were the most frequent allergens (20% of food allergens in each case). Severe reactions with cardiovascular involvement occurred in 24% of cases. No fatal reaction was observed. Recurrent episodes of anaphylaxis were reported in 27% of cases, half of these caused by the same allergen again. For treatment, 20% of children received adrenaline, in 8% of cases intravenously. Thirty-six per cent of patients with grade-IV reactions received adrenaline, 24% intravenously. In 17% of all children an adrenaline self-injector was prescribed after the episode. Conclusion: Our data: (i) shows an uncertainty of physicians in diagnosing anaphylaxis, (ii) reveals remarkable under-treatment of the majority of children with anaphylaxis, (iii) reflects the need for guidelines and training for physicians in managing children with anaphylaxis and (iv) should encourage the development of self-management programmes for patients and families.. anaphylaxis| children| food allergy| immunotherapy| infants| insect sting allergy|allergic diseases| food allergy| immunotherapy| epidemiology| fatalities| features.	NOV-2005	anaphylaxis| children| food allergy| immunotherapy| infants| insect sting allergy|allergic diseases| food allergy| immunotherapy| epidemiology| fatalities| features	Mehl, A; Wahn, U; Niggemann, B	Anaphylactic reactions in children - a questionnaire-based survey in Germany		ALLERGY	anaphylaxis; children; food allergy; immunotherapy; infants; insect sting allergy	ALLERGIC DISEASES; FOOD ALLERGY; IMMUNOTHERAPY; EPIDEMIOLOGY; FATALITIES; FEATURES	Background: Severe anaphylactic reactions are medical emergencies requiring immediate recognition and treatment. Despite this, little is known on their clinical features, especially in infants and children. Objective: To evaluate trigger factors, patterns of clinical reaction, site of occurrence and treatment modalities of reported reaction in infants and children below 12 years of age in Germany. Methods: Paediatricians throughout Germany were asked by questionnaire to report accidental anaphylactic reactions over the previous 12 months. Severity of reported reactions was classified in grades I-IV according to reported symptoms. Results: Hundred and three cases of anaphylaxis were evaluated. Median age was 5 years, 58% were boys. Site of occurrence was the child's home in the majority of cases (58%). Foods were the most common causative allergen (57%), followed by insect stings (13%) and immunotherapy (SIT) (12%); in 8% anaphylactic agent was unknown. Among foods, peanuts and tree nuts were the most frequent allergens (20% of food allergens in each case). Severe reactions with cardiovascular involvement occurred in 24% of cases. No fatal reaction was observed. Recurrent episodes of anaphylaxis were reported in 27% of cases, half of these caused by the same allergen again. For treatment, 20% of children received adrenaline, in 8% of cases intravenously. Thirty-six per cent of patients with grade-IV reactions received adrenaline, 24% intravenously. In 17% of all children an adrenaline self-injector was prescribed after the episode. Conclusion: Our data: (i) shows an uncertainty of physicians in diagnosing anaphylaxis, (ii) reveals remarkable under-treatment of the majority of children with anaphylaxis, (iii) reflects the need for guidelines and training for physicians in managing children with anaphylaxis and (iv) should encourage the development of self-management programmes for patients and families.	26	112	2005	6	10.1111/j.1398-9995.2005.00909.x	Allergy; Immunology
Contact allergy to fragrances: frequencies of sensitization from 1996 to 2002. Results of the IVDK. Increasing frequencies of sensitization to the fragrance mix (FM) have been acknowledged as a serious problem for many years. It is well known that the single compounds (SCs) of the FM contribute differently to the FM patch rest reactions. In this study, we were interested in the time trends of the FM, the SCs, Myroxylon pereirae resin (MP; balsam of Peru) and oil of turpentine (OT) as possible further indicators of perfume allergy and analysed the data collected by the Information Network of Departments of Dermatology multicentre project from 1996 to 2002. During the study period (1996-2002), the FM [8% petrolatum (pet.)], MP (25% pet.) and OT (1% pet.) were tested in 59 298, 59 334 and 59 478 patients, respectively. SCs were tested in a selected group of patients, ranging from n = 1083 to n = 1924 per year. A significant increase in the proportions of patients with positive reactions to FM, MP and OT between 1996 and 1998 is noted, and a significant decline from 1999 to 2002 (Cochrane Armitage trend test, P < 0.0001). The highest frequency of sensitization to the FM was 13.1% in 1999, and the lowest 7.8% in 2002. The number of concomitant reactions to OT, a surrogate marker for terpenes, in FM-positive patients was significantly increased between 1997 and 1999. Reactions to SCs in FM-positive patients were observed in 29.9% (oak moss absolute) to 5.9% (geraniol). There was no time trend in reactions to SCs, although the relative share was increased for isoeugenol, cinnamic aldehyde and geraniol in 1999. In summary, we report for the first time, a significant decline in sensitization to the FM, very probably due to a reduced exposure (less potent allergens used in fine fragrances, possibly less use of natural ingredient-based cosmetics and lowered use concentration of important fragrance allergens). The differences in ranking of SCs could stimulate (a) a redefinition of the FM and (b) a differentiated preventive and regulatory approach, with oak moss and isoeugenol being regulated strictly by prohibition, concentration limits further reconsidered and/or health warnings and clearly less noxious substances like geraniol treated less restrictively.. contact allergy| fragrance mix| frequency of sensitization| multicentre study| myroxylon pereirae resin| oil of turpentine|patch-test| information network| standard series| dermatology ivdk| skin-sensitization| chemical-analysis| essential oils| dermatitis| multicenter| perfumes.	FEB-2004	contact allergy| fragrance mix| frequency of sensitization| multicentre study| myroxylon pereirae resin| oil of turpentine|patch-test| information network| standard series| dermatology ivdk| skin-sensitization| chemical-analysis| essential oils| dermatitis| multicenter| perfumes	Schnuch, A; Lessmann, H; Geier, J; Frosch, PJ; Uter, W	Contact allergy to fragrances: frequencies of sensitization from 1996 to 2002. Results of the IVDK		CONTACT DERMATITIS	contact allergy; fragrance mix; frequency of sensitization; multicentre study; Myroxylon pereirae resin; oil of turpentine	PATCH-TEST; INFORMATION NETWORK; STANDARD SERIES; DERMATOLOGY IVDK; SKIN-SENSITIZATION; CHEMICAL-ANALYSIS; ESSENTIAL OILS; DERMATITIS; MULTICENTER; PERFUMES	Increasing frequencies of sensitization to the fragrance mix (FM) have been acknowledged as a serious problem for many years. It is well known that the single compounds (SCs) of the FM contribute differently to the FM patch rest reactions. In this study, we were interested in the time trends of the FM, the SCs, Myroxylon pereirae resin (MP; balsam of Peru) and oil of turpentine (OT) as possible further indicators of perfume allergy and analysed the data collected by the Information Network of Departments of Dermatology multicentre project from 1996 to 2002. During the study period (1996-2002), the FM [8% petrolatum (pet.)], MP (25% pet.) and OT (1% pet.) were tested in 59 298, 59 334 and 59 478 patients, respectively. SCs were tested in a selected group of patients, ranging from n = 1083 to n = 1924 per year. A significant increase in the proportions of patients with positive reactions to FM, MP and OT between 1996 and 1998 is noted, and a significant decline from 1999 to 2002 (Cochrane Armitage trend test, P < 0.0001). The highest frequency of sensitization to the FM was 13.1% in 1999, and the lowest 7.8% in 2002. The number of concomitant reactions to OT, a surrogate marker for terpenes, in FM-positive patients was significantly increased between 1997 and 1999. Reactions to SCs in FM-positive patients were observed in 29.9% (oak moss absolute) to 5.9% (geraniol). There was no time trend in reactions to SCs, although the relative share was increased for isoeugenol, cinnamic aldehyde and geraniol in 1999. In summary, we report for the first time, a significant decline in sensitization to the FM, very probably due to a reduced exposure (less potent allergens used in fine fragrances, possibly less use of natural ingredient-based cosmetics and lowered use concentration of important fragrance allergens). The differences in ranking of SCs could stimulate (a) a redefinition of the FM and (b) a differentiated preventive and regulatory approach, with oak moss and isoeugenol being regulated strictly by prohibition, concentration limits further reconsidered and/or health warnings and clearly less noxious substances like geraniol treated less restrictively.	74	112	2004	12	10.1111/j.0105-1873.2004.00302.x	Allergy; Dermatology
Sensitization to fungi: epidemiology, comparative skin tests, and IgE reactivity of fungal extracts. Background Several fungal species are known to cause severe respiratory and cutaneous allergic diseases. Extracts from several allergenic fungi are used for in vivo and in vitro tests, as standard preparations are still not available. Objective The aims are to de. ne the pattern of in vivo and in vitro IgE reactivity to fungal species in an allergic population with respiratory symptoms; to determine the influence of different extract preparations on diagnostic results; and to evaluate whether there exists a relationship between the diagnostic pattern of reactivity and the pattern of specific IgE reactivity in immunoblots. Methods Skin prick tests were applied to a cohort of 4962 respiratory subjects, aged 3 - 80 years. Fungal extracts from Alternaria, Aspergillus, Candida, Cladosporium, Penicillium, Saccharomyces, and Trichophyton were used, along with extracts from pollens, mites, and animal dander. Demographical and diagnostic data were recorded. IgE detection was carried out with the same allergenic extracts plus Malassezia. Comparative skin tests and IgE detection were carried out using extracts from three commercial suppliers. IgE immunoblots were carried out with the same panel of commercial fungal extracts and were compared with in-house extracts. Data analysis was carried out by grouping the population on the basis of their reactivity to a single, to two or to more than two, mould species. Results Nineteen percent of the allergic population reacted to at least one fungal extract by means of the skin test. Alternaria and Candida accounted for the largest number of positive tests, and along with Trichophyton they were the main sensitizers in the subset of patients with an isolated sensitization. The prevalence of skin test reactivity increased for these three fungi in the subsets with two associated reactivities and, furthermore, in the subset showing reactivity to more than two mould species. In the latter group, a steady increase of the skin test reactivity was recorded for all the other fungal sources, suggesting a clustered reactivity. Comparative skin and IgE testing with different groups of subjects with a simple pattern of skin reactivity resulted in sensitivity differences between in vivo and in vitro tests, whereas discrepant results were recorded in the subsets of patients with multiple fungi sensitization. Although hampered by the limited reliability of fungal extracts, IgE immunoblots revealed differing patterns of reactivity when sera from the three subsets were used. This suggests a link between the diagnostic reactivity pattern and the IgE sensitization to extracts' components. Age and gender distribution differed among the Alternaria-, Candida-, and Trichophyton-sensitized subjects, but not in the subset with more than two fungi sensitizations. Conclusions The preliminary assessment of a new classification of the mould-sensitized population has been reached. The limiting quality of fungal extracts requires future studies using an allergenic molecule-based approach. The diagnostic process and the definition of the reactivity pattern would thus be easy, and it could lead to a novel specific immunotherapy approach.. allergens| comparative study| epidemiology| fungal allergy diagnosis| fungal extract| ige detection| immunoblotting| prevalence| skin tests|candida-albicans| alternaria-alternata| immunological characterization| aspergillus-fumigatus| cross-reactivity| cladosporium-herbarum| penicillium-citrinum| vaginal candidiasis| respiratory allergy| desert environment.	OCT-2003	allergens| comparative study| epidemiology| fungal allergy diagnosis| fungal extract| ige detection| immunoblotting| prevalence| skin tests|candida-albicans| alternaria-alternata| immunological characterization| aspergillus-fumigatus| cross-reactivity| cladosporium-herbarum| penicillium-citrinum| vaginal candidiasis| respiratory allergy| desert environment	Mari, A; Schneider, P; Wally, V; Breitenbach, M; Simon-Nobbe, B	Sensitization to fungi: epidemiology, comparative skin tests, and IgE reactivity of fungal extracts		CLINICAL AND EXPERIMENTAL ALLERGY	allergens; comparative study; epidemiology; fungal allergy diagnosis; fungal extract; IgE detection; immunoblotting; prevalence; skin tests	CANDIDA-ALBICANS; ALTERNARIA-ALTERNATA; IMMUNOLOGICAL CHARACTERIZATION; ASPERGILLUS-FUMIGATUS; CROSS-REACTIVITY; CLADOSPORIUM-HERBARUM; PENICILLIUM-CITRINUM; VAGINAL CANDIDIASIS; RESPIRATORY ALLERGY; DESERT ENVIRONMENT	Background Several fungal species are known to cause severe respiratory and cutaneous allergic diseases. Extracts from several allergenic fungi are used for in vivo and in vitro tests, as standard preparations are still not available. Objective The aims are to de. ne the pattern of in vivo and in vitro IgE reactivity to fungal species in an allergic population with respiratory symptoms; to determine the influence of different extract preparations on diagnostic results; and to evaluate whether there exists a relationship between the diagnostic pattern of reactivity and the pattern of specific IgE reactivity in immunoblots. Methods Skin prick tests were applied to a cohort of 4962 respiratory subjects, aged 3 - 80 years. Fungal extracts from Alternaria, Aspergillus, Candida, Cladosporium, Penicillium, Saccharomyces, and Trichophyton were used, along with extracts from pollens, mites, and animal dander. Demographical and diagnostic data were recorded. IgE detection was carried out with the same allergenic extracts plus Malassezia. Comparative skin tests and IgE detection were carried out using extracts from three commercial suppliers. IgE immunoblots were carried out with the same panel of commercial fungal extracts and were compared with in-house extracts. Data analysis was carried out by grouping the population on the basis of their reactivity to a single, to two or to more than two, mould species. Results Nineteen percent of the allergic population reacted to at least one fungal extract by means of the skin test. Alternaria and Candida accounted for the largest number of positive tests, and along with Trichophyton they were the main sensitizers in the subset of patients with an isolated sensitization. The prevalence of skin test reactivity increased for these three fungi in the subsets with two associated reactivities and, furthermore, in the subset showing reactivity to more than two mould species. In the latter group, a steady increase of the skin test reactivity was recorded for all the other fungal sources, suggesting a clustered reactivity. Comparative skin and IgE testing with different groups of subjects with a simple pattern of skin reactivity resulted in sensitivity differences between in vivo and in vitro tests, whereas discrepant results were recorded in the subsets of patients with multiple fungi sensitization. Although hampered by the limited reliability of fungal extracts, IgE immunoblots revealed differing patterns of reactivity when sera from the three subsets were used. This suggests a link between the diagnostic reactivity pattern and the IgE sensitization to extracts' components. Age and gender distribution differed among the Alternaria-, Candida-, and Trichophyton-sensitized subjects, but not in the subset with more than two fungi sensitizations. Conclusions The preliminary assessment of a new classification of the mould-sensitized population has been reached. The limiting quality of fungal extracts requires future studies using an allergenic molecule-based approach. The diagnostic process and the definition of the reactivity pattern would thus be easy, and it could lead to a novel specific immunotherapy approach.	48	112	2003	10	10.1046/j.1365-2222.2003.01783.x	Allergy; Immunology
Health and socioeconomic impact of work-related asthma. There is accumulating evidence that the workplace environment contributes significantly to the general burden of asthma. The purpose of this review is to explore the respiratory health and socioeconomic consequences of work-related asthma by addressing a series of controversial issues: 1) what is the natural history of occupational asthma and in what ways does ongoing exposure to the causal agent impact clinical outcomes?; 2) how does the natural history of irritant-induced asthma differ in its health outcomes from immunologically-mediated occupational asthma?; 3) do working conditions have a significant impact on asthma regardless of the aetiology of the disease?; 4) what is the scope of work disability from work-related-asthma in social and economic terms?; 5) what is the clinician's role in reducing the respiratory health consequences of work-related asthma? 6) to what extent do existing compensation and other social insurance schemes successfully address occupational asthma and work-aggravated asthma?. asthma| disability| occupational disease|airways dysfunction syndrome| diisocyanate-induced asthma| induced occupational asthma| toluene diisocyanate| follow-up| bronchial hyperresponsiveness| persistent asthma| repeated exposure| inhalation challenge| chlorine inhalation.	OCT-2003	asthma| disability| occupational disease|airways dysfunction syndrome| diisocyanate-induced asthma| induced occupational asthma| toluene diisocyanate| follow-up| bronchial hyperresponsiveness| persistent asthma| repeated exposure| inhalation challenge| chlorine inhalation	Vandenplas, O; Toren, K; Blanc, PD	Health and socioeconomic impact of work-related asthma		EUROPEAN RESPIRATORY JOURNAL	asthma; disability; occupational disease	AIRWAYS DYSFUNCTION SYNDROME; DIISOCYANATE-INDUCED ASTHMA; INDUCED OCCUPATIONAL ASTHMA; TOLUENE DIISOCYANATE; FOLLOW-UP; BRONCHIAL HYPERRESPONSIVENESS; PERSISTENT ASTHMA; REPEATED EXPOSURE; INHALATION CHALLENGE; CHLORINE INHALATION	There is accumulating evidence that the workplace environment contributes significantly to the general burden of asthma. The purpose of this review is to explore the respiratory health and socioeconomic consequences of work-related asthma by addressing a series of controversial issues: 1) what is the natural history of occupational asthma and in what ways does ongoing exposure to the causal agent impact clinical outcomes?; 2) how does the natural history of irritant-induced asthma differ in its health outcomes from immunologically-mediated occupational asthma?; 3) do working conditions have a significant impact on asthma regardless of the aetiology of the disease?; 4) what is the scope of work disability from work-related-asthma in social and economic terms?; 5) what is the clinician's role in reducing the respiratory health consequences of work-related asthma? 6) to what extent do existing compensation and other social insurance schemes successfully address occupational asthma and work-aggravated asthma?	111	112	2003	9	10.1183/09031936.03.00053203	Respiratory System
Platelets are essential for leukocyte recruitment in allergic inflammation. Background: The role of platelets in inflammation is recognized but poorly characterized, and little is known of their interaction with leukocytes. However, platelet-leukocyte interactions have been demonstrated in cardiovascular disease, culminating in enhanced leukocyte recruitment. Objectives: This study was undertaken to assess the possibility and potential role of similar phenomena occurring in asthmatic patients, a murine model of allergic inflammation, and in vitro adhesion studies. Methods: Asthmatic patients had blood taken at various time points to document the degree of leukocyte activation and the presence of platelet-leukocyte aggregates through FACS analysis before and after allergen exposure. Similar studies were carried out in mice exposed to allergen after previous sensitization, with some groups being selectively depleted of platelets through both an immunologic (antiplatelet antiserum) and nonimmunologic (busulfan) method. Additionally, lavage fluid and airway tissue were analyzed to assess the degree of pulmonary leukocyte recruitment. The importance of platelets on leukocyte adhesion to the endothelium was then assessed with in vitro incubation of radiolabeled leukocytes in the presence of activated platelets on cultured human vascular endothelial cells. Results: We have observed circulating platelet-leukocyte aggregates in the blood of allergic asthmatic patients during the allergen-induced late asthmatic response and in sensitized mice after allergen exposure. In platelet-depleted mice infiltration of leukocytes into airways after allergen challenge was significantly reduced and could be restored by means of infusion of platelets from allergic animals, indicating an essential role for platelets in leukocyte recruitment. CD11b expression on leukocytes involved in aggregates with platelets, although not on free leukocytes, was upregulated. Furthermore, the presence of autologous platelets augmented the adhesion of human polymorphonuclear leukocytes to cultured vascular endothelial cells, an effect that was found to be endothelial cell dependent and to involve platelet activation. Conclusion: These results suggest that platelet participation in cell recruitment occurs at the level of the circulation and might involve the priming of leukocytes for subsequent adhesion and transmigration into tissues.. platelet| leukocyte| platelet-leukocyte interaction| asthma| allergy| eosinophil| lymphocyte| vascular endothelium| cd11b|p-selectin| flow-cytometry| whole-blood| asthma| adhesion| activation| neutrophils| cells| paf| aggregation.	JUL-2003	platelet| leukocyte| platelet-leukocyte interaction| asthma| allergy| eosinophil| lymphocyte| vascular endothelium| cd11b|p-selectin| flow-cytometry| whole-blood| asthma| adhesion| activation| neutrophils| cells| paf| aggregation	Pitchford, SC; Yano, H; Lever, R; Riffo-Vasquez, Y; Ciferri, S; Rose, MJ; Giannini, S; Momi, S; Spina, D; O'Connor, B; Gresele, P; Page, CP	Platelets are essential for leukocyte recruitment in allergic inflammation		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	platelet; leukocyte; platelet-leukocyte interaction; asthma; allergy; eosinophil; lymphocyte; vascular endothelium; CD11b	P-SELECTIN; FLOW-CYTOMETRY; WHOLE-BLOOD; ASTHMA; ADHESION; ACTIVATION; NEUTROPHILS; CELLS; PAF; AGGREGATION	Background: The role of platelets in inflammation is recognized but poorly characterized, and little is known of their interaction with leukocytes. However, platelet-leukocyte interactions have been demonstrated in cardiovascular disease, culminating in enhanced leukocyte recruitment. Objectives: This study was undertaken to assess the possibility and potential role of similar phenomena occurring in asthmatic patients, a murine model of allergic inflammation, and in vitro adhesion studies. Methods: Asthmatic patients had blood taken at various time points to document the degree of leukocyte activation and the presence of platelet-leukocyte aggregates through FACS analysis before and after allergen exposure. Similar studies were carried out in mice exposed to allergen after previous sensitization, with some groups being selectively depleted of platelets through both an immunologic (antiplatelet antiserum) and nonimmunologic (busulfan) method. Additionally, lavage fluid and airway tissue were analyzed to assess the degree of pulmonary leukocyte recruitment. The importance of platelets on leukocyte adhesion to the endothelium was then assessed with in vitro incubation of radiolabeled leukocytes in the presence of activated platelets on cultured human vascular endothelial cells. Results: We have observed circulating platelet-leukocyte aggregates in the blood of allergic asthmatic patients during the allergen-induced late asthmatic response and in sensitized mice after allergen exposure. In platelet-depleted mice infiltration of leukocytes into airways after allergen challenge was significantly reduced and could be restored by means of infusion of platelets from allergic animals, indicating an essential role for platelets in leukocyte recruitment. CD11b expression on leukocytes involved in aggregates with platelets, although not on free leukocytes, was upregulated. Furthermore, the presence of autologous platelets augmented the adhesion of human polymorphonuclear leukocytes to cultured vascular endothelial cells, an effect that was found to be endothelial cell dependent and to involve platelet activation. Conclusion: These results suggest that platelet participation in cell recruitment occurs at the level of the circulation and might involve the priming of leukocytes for subsequent adhesion and transmigration into tissues.	46	112	2003	10	10.1067/mai.2003.1514	Allergy; Immunology
Allergen-induced airway disease is mouse strain dependent. We investigated the development of airway hyperreactivity ( AHR) and inflammation in the lungs of nine genetically diverse inbred strains of mice [129/SvIm, A/J, BALB/cJ, BTBR+(T)/tf/tf, CAST/Ei, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ] after sensitization and challenge with ovalbumin (OVA). At 24, 48, and 72 h post-OVA exposure, the severity of AHR and eosinophilic inflammation of the mouse strains ranged from relatively unresponsive to responsive. The severity of the airway eosinophilia of some strains did not clearly correlate with the development of AHR. The temporal presence of T helper type 2 cytokines in lung lavage fluid also varied markedly among the strains. The levels of IL-4 and IL-13 were generally increased in the strains with the highest airway eosinophilia at 24 and 72 h postexposure, respectively; the levels of IL-5 were significantly increased in most of the strains with airway inflammation over the 72-h time period. The differences of physiological and biological responses among the inbred mouse strains after OVA sensitization and challenge support the hypothesis that genetic factors contribute, in part, to the development of allergen-induced airway disease.. asthma| airway hyperreactivity| eosinophils| cytokines|late asthmatic reactions| lung damage| mice| hyperresponsiveness| hyperreactivity| interleukin-5| inflammation| responsiveness| eosinophilia| neutrophils.	JUL-2003	asthma| airway hyperreactivity| eosinophils| cytokines|late asthmatic reactions| lung damage| mice| hyperresponsiveness| hyperreactivity| interleukin-5| inflammation| responsiveness| eosinophilia| neutrophils	Whitehead, GS; Walker, JKL; Berman, KG; Foster, WM; Schwartz, DA	Allergen-induced airway disease is mouse strain dependent		AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY	asthma; airway hyperreactivity; eosinophils; cytokines	LATE ASTHMATIC REACTIONS; LUNG DAMAGE; MICE; HYPERRESPONSIVENESS; HYPERREACTIVITY; INTERLEUKIN-5; INFLAMMATION; RESPONSIVENESS; EOSINOPHILIA; NEUTROPHILS	We investigated the development of airway hyperreactivity ( AHR) and inflammation in the lungs of nine genetically diverse inbred strains of mice [129/SvIm, A/J, BALB/cJ, BTBR+(T)/tf/tf, CAST/Ei, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ] after sensitization and challenge with ovalbumin (OVA). At 24, 48, and 72 h post-OVA exposure, the severity of AHR and eosinophilic inflammation of the mouse strains ranged from relatively unresponsive to responsive. The severity of the airway eosinophilia of some strains did not clearly correlate with the development of AHR. The temporal presence of T helper type 2 cytokines in lung lavage fluid also varied markedly among the strains. The levels of IL-4 and IL-13 were generally increased in the strains with the highest airway eosinophilia at 24 and 72 h postexposure, respectively; the levels of IL-5 were significantly increased in most of the strains with airway inflammation over the 72-h time period. The differences of physiological and biological responses among the inbred mouse strains after OVA sensitization and challenge support the hypothesis that genetic factors contribute, in part, to the development of allergen-induced airway disease.	48	112	2003	11	10.1152/ajplung.00390.2002	Physiology; Respiratory System
Muscarinic acetylcholine receptors and airway diseases. Parasympathetic nerves provide the dominant autonomic innervation of the airways. Release of acetylcholine from parasympathetic nerves activates postjunctional muscarinic receptors present on airway smooth muscle, submucosal glands, and blood vessels to cause bronchoconstriction, mucus secretion, and vasodilatation, respectively. Acetylcholine also feeds back onto prejunctional muscarinic receptors to enhance or inhibit further acetylcholine release. In asthma and chronic obstructive pulmonary disease, bronchoconstriction and mucus secretion is increased and the airways are hyperresponsive to contractile agents. These changes are due to increased parasympathetic nerve activity. The number and function of postjunctional muscarinic receptors in the airways are unchanged in animal models of asthma. Rather, it is the supply of acetylcholine to the postjunctional cells (smooth muscle and submucosal gland) that is increased. The increase in acetylcholine release occurs because prejunctional, inhibitory M-2 muscarinic receptors on the parasympathetic nerves are dysfunctional. M-2 muscarinic receptor dysfunction and subsequent airway hyperreactivity have been demonstrated to occur in animals in response to a variety of triggers, including antigen challenge, virus infection, ozone exposure, and vitamin A deficiency. In humans, there is evidence that loss of M-2 muscarinic receptor function is related to asthma. The mechanisms by which neuronal M-2 muscarinic receptor function is lost and its relevance to human airway disease are discussed in this review. (C) 2003 Elsevier Science Inc. All rights reserved.. prejunctional receptors| postjunctional receptors| parasympathetic nerves| airway hyperreactivity| eosinophils| viruses|obstructive pulmonary-disease| upper respiratory-tract| major basic-protein| guinea-pig trachea| induced bronchial hyperreactivity| inhaled ipratropium bromide| exercise-induced asthma| vitamin-a-deficiency| smooth-muscle| induced bronchoconstriction.	APR-2003	prejunctional receptors| postjunctional receptors| parasympathetic nerves| airway hyperreactivity| eosinophils| viruses|obstructive pulmonary-disease| upper respiratory-tract| major basic-protein| guinea-pig trachea| induced bronchial hyperreactivity| inhaled ipratropium bromide| exercise-induced asthma| vitamin-a-deficiency| smooth-muscle| induced bronchoconstriction	Coulson, FR; Fryer, AD	Muscarinic acetylcholine receptors and airway diseases		PHARMACOLOGY & THERAPEUTICS	prejunctional receptors; postjunctional receptors; parasympathetic nerves; airway hyperreactivity; eosinophils; viruses	OBSTRUCTIVE PULMONARY-DISEASE; UPPER RESPIRATORY-TRACT; MAJOR BASIC-PROTEIN; GUINEA-PIG TRACHEA; INDUCED BRONCHIAL HYPERREACTIVITY; INHALED IPRATROPIUM BROMIDE; EXERCISE-INDUCED ASTHMA; VITAMIN-A-DEFICIENCY; SMOOTH-MUSCLE; INDUCED BRONCHOCONSTRICTION	Parasympathetic nerves provide the dominant autonomic innervation of the airways. Release of acetylcholine from parasympathetic nerves activates postjunctional muscarinic receptors present on airway smooth muscle, submucosal glands, and blood vessels to cause bronchoconstriction, mucus secretion, and vasodilatation, respectively. Acetylcholine also feeds back onto prejunctional muscarinic receptors to enhance or inhibit further acetylcholine release. In asthma and chronic obstructive pulmonary disease, bronchoconstriction and mucus secretion is increased and the airways are hyperresponsive to contractile agents. These changes are due to increased parasympathetic nerve activity. The number and function of postjunctional muscarinic receptors in the airways are unchanged in animal models of asthma. Rather, it is the supply of acetylcholine to the postjunctional cells (smooth muscle and submucosal gland) that is increased. The increase in acetylcholine release occurs because prejunctional, inhibitory M-2 muscarinic receptors on the parasympathetic nerves are dysfunctional. M-2 muscarinic receptor dysfunction and subsequent airway hyperreactivity have been demonstrated to occur in animals in response to a variety of triggers, including antigen challenge, virus infection, ozone exposure, and vitamin A deficiency. In humans, there is evidence that loss of M-2 muscarinic receptor function is related to asthma. The mechanisms by which neuronal M-2 muscarinic receptor function is lost and its relevance to human airway disease are discussed in this review. (C) 2003 Elsevier Science Inc. All rights reserved.	166	112	2003	11	10.1016/S0163-7258(03)00004-4	Pharmacology & Pharmacy
Breast feeding and a birth cohort study respiratory morbidity in infancy: a birth cohort study. Aim: To examine the relation between the duration of breast feeding and morbidity as a result of respiratory illness and infection in the first year of life. Methods: Prospective birth cohort study of 2602 live born children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia. Main outcome measures were hospital, doctor, or clinic visits, and hospital admissions for respiratory illness and infection in the first year of life. Main exposure measures were the duration of predominant breast feeding (defined as the age other milk was introduced) and partial (any) breast feeding (defined as the age breast feeding was stopped). Main confounders were gender, gestational age less than 37 weeks, smoking in pregnancy, older siblings, maternal education, and maternal age. Results: Hospital, doctor, or clinic visits for four or more upper respiratory tract infections were significantly greater if predominant breast feeding was stopped before 2 months or partial breast feeding was stopped before 6 months. Predominant breast feeding for less than six months was associated with an increased risk for two or more hospital, doctor, or clinic visits and hospital admission for wheezing, lower respiratory illness. Breast feeding for less than eight months was associated with a significantly increased risk for two or more hospital, doctor, or clinic visits or hospital admissions because of wheezing lower respiratory illnesses. Conclusions: Predominant breast feeding for at least six months and partial breast feeding for up to one year may reduce the prevalence and subsequent morbidity of respiratory illness and infection in infancy.. formula-fed infants| 1st year| tract illness| otitis-media| human-milk| follow-up| life| infections| childhood| asthma.	MAR-2003	formula-fed infants| 1st year| tract illness| otitis-media| human-milk| follow-up| life| infections| childhood| asthma	Oddy, WH; Sly, PD; de Klerk, NH; Landau, LI; Kendall, GE; Holt, PG; Stanley, FJ	Breast feeding and a birth cohort study respiratory morbidity in infancy: a birth cohort study		ARCHIVES OF DISEASE IN CHILDHOOD		FORMULA-FED INFANTS; 1ST YEAR; TRACT ILLNESS; OTITIS-MEDIA; HUMAN-MILK; FOLLOW-UP; LIFE; INFECTIONS; CHILDHOOD; ASTHMA	Aim: To examine the relation between the duration of breast feeding and morbidity as a result of respiratory illness and infection in the first year of life. Methods: Prospective birth cohort study of 2602 live born children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia. Main outcome measures were hospital, doctor, or clinic visits, and hospital admissions for respiratory illness and infection in the first year of life. Main exposure measures were the duration of predominant breast feeding (defined as the age other milk was introduced) and partial (any) breast feeding (defined as the age breast feeding was stopped). Main confounders were gender, gestational age less than 37 weeks, smoking in pregnancy, older siblings, maternal education, and maternal age. Results: Hospital, doctor, or clinic visits for four or more upper respiratory tract infections were significantly greater if predominant breast feeding was stopped before 2 months or partial breast feeding was stopped before 6 months. Predominant breast feeding for less than six months was associated with an increased risk for two or more hospital, doctor, or clinic visits and hospital admission for wheezing, lower respiratory illness. Breast feeding for less than eight months was associated with a significantly increased risk for two or more hospital, doctor, or clinic visits or hospital admissions because of wheezing lower respiratory illnesses. Conclusions: Predominant breast feeding for at least six months and partial breast feeding for up to one year may reduce the prevalence and subsequent morbidity of respiratory illness and infection in infancy.	39	112	2003	5	10.1136/adc.88.3.224	Pediatrics
Environmental factors influencing the development and progression of pediatric asthma. Recent data underscore the importance of environmental factors in the sensitization of children to certain allergens and the development of asthma. Maternal smoking and family (especially maternal) history of atopy appear to be risk factors for persistent sensitization and development of asthma. Indeed, exposure to tobacco smoke in utero significantly increases asthma risk and influences the timing of sensitization. It must be stated that any smoking at home has consequences for the development of asthma and other respiratory conditions. In addition, reports of possible protective effects of specific environmental conditions suggest that exposure to certain stimuli may reduce or block the development and progression of asthma. Attendance at a day care center early in life appears to offer protective effects against wheezing, as do early episodes of rhinitis, herpes, and measles. Children raised on a farm also have a decreased prevalence of atopic diseases. The protective effect of contact with livestock and poultry is consistent among several studies. Although the pathophysiologic mechanisms involved remain undefined, studies suggest that exposure to endotoxin and other components of bacteria may play an important role in protecting against childhood atopic diseases. Whether in utero exposure is beneficial remains to be determined.. asthma| atopy| environmental factors| risk factors| sensitization|allergic sensitization| hay-fever| early-childhood| children| exposure| cohort| risk| age| prevalence| community.	JUN-2002	asthma| atopy| environmental factors| risk factors| sensitization|allergic sensitization| hay-fever| early-childhood| children| exposure| cohort| risk| age| prevalence| community	von Mutius, E	Environmental factors influencing the development and progression of pediatric asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; atopy; environmental factors; risk factors; sensitization	ALLERGIC SENSITIZATION; HAY-FEVER; EARLY-CHILDHOOD; CHILDREN; EXPOSURE; COHORT; RISK; AGE; PREVALENCE; COMMUNITY	Recent data underscore the importance of environmental factors in the sensitization of children to certain allergens and the development of asthma. Maternal smoking and family (especially maternal) history of atopy appear to be risk factors for persistent sensitization and development of asthma. Indeed, exposure to tobacco smoke in utero significantly increases asthma risk and influences the timing of sensitization. It must be stated that any smoking at home has consequences for the development of asthma and other respiratory conditions. In addition, reports of possible protective effects of specific environmental conditions suggest that exposure to certain stimuli may reduce or block the development and progression of asthma. Attendance at a day care center early in life appears to offer protective effects against wheezing, as do early episodes of rhinitis, herpes, and measles. Children raised on a farm also have a decreased prevalence of atopic diseases. The protective effect of contact with livestock and poultry is consistent among several studies. Although the pathophysiologic mechanisms involved remain undefined, studies suggest that exposure to endotoxin and other components of bacteria may play an important role in protecting against childhood atopic diseases. Whether in utero exposure is beneficial remains to be determined.	19	112	2002	8	10.1067/mai.2002.124565	Allergy; Immunology
Reactive nitrogen and human health: Acute and long-term implications. Reactive-nitrogen (Nr) has a wide variety of beneficial and detrimental effects on human health. The most important of the beneficial effects are increasing global and regional food supplies and increased nutritional quality of available foods. However, lack of adequate dietary intake of amino acids and proteins is a serious cause of malnutrition when food supplies are inadequate because of poverty, drought, floods, wars, and displacements of people as refugees. There is sufficient, though limited, quantitative data indicating that increased circulation of Nr in the environment is responsible for significant human health effects via other exposure pathways. Nr can lead to harmful health effects from airborne occupational exposures and population-wide indoor and outdoor air pollution exposures to nitrogen dioxide and ozone. Nr can also affect health via water pollution problems, including methemoglobinemia from contaminated ground water, eutrophication causing fish kills and algal blooms that can be toxic to humans, and via global warming. The environmental pollutants stemming from reactive nitrogen are ubiquitous, making it difficult to identify the extent to which Nr exerts a specific health effect. As all populations are susceptible, continued interdisciplinary investigations are needed to determine the extent and nature of the beneficial and harmful effects on human health of nitrogen-related pollutants and their derivatives.. outdoor air-pollution| public-health| drinking-water| dioxide| asthma| ozone| contamination| environment| admissions| management.	MAR-2002	outdoor air-pollution| public-health| drinking-water| dioxide| asthma| ozone| contamination| environment| admissions| management	Wolfe, AH; Patz, JA	Reactive nitrogen and human health: Acute and long-term implications		AMBIO		OUTDOOR AIR-POLLUTION; PUBLIC-HEALTH; DRINKING-WATER; DIOXIDE; ASTHMA; OZONE; CONTAMINATION; ENVIRONMENT; ADMISSIONS; MANAGEMENT	Reactive-nitrogen (Nr) has a wide variety of beneficial and detrimental effects on human health. The most important of the beneficial effects are increasing global and regional food supplies and increased nutritional quality of available foods. However, lack of adequate dietary intake of amino acids and proteins is a serious cause of malnutrition when food supplies are inadequate because of poverty, drought, floods, wars, and displacements of people as refugees. There is sufficient, though limited, quantitative data indicating that increased circulation of Nr in the environment is responsible for significant human health effects via other exposure pathways. Nr can lead to harmful health effects from airborne occupational exposures and population-wide indoor and outdoor air pollution exposures to nitrogen dioxide and ozone. Nr can also affect health via water pollution problems, including methemoglobinemia from contaminated ground water, eutrophication causing fish kills and algal blooms that can be toxic to humans, and via global warming. The environmental pollutants stemming from reactive nitrogen are ubiquitous, making it difficult to identify the extent to which Nr exerts a specific health effect. As all populations are susceptible, continued interdisciplinary investigations are needed to determine the extent and nature of the beneficial and harmful effects on human health of nitrogen-related pollutants and their derivatives.	62	112	2002	6	10.1639/0044-7447(2002)031[0120:RNAHHA]2.0.CO;2	Engineering; Environmental Sciences & Ecology
Rising CO2 and pollen production of common ragweed (Ambrosia artemisiifolia), a known allergy-inducing species: implications for public health. Although environmental factors such as precipitation and temperature are recognized as influencing pollen production, the impact of rising atmospheric carbon dioxide concentration ([ CO2]) on the potential growth and pollen production of hay- fever- inducing plants is unknown. Here we present measurements of growth and pollen production of common ragweed (Ambrosia artemisiifolia L.) from pre- industrial [CO2] (280 mu mol mol(-1)) to current concentrations (370 mu mol mol(-1)) to a projected 21st century concentration (600 mu mol mol(-1)). We found that exposure to current and elevated [CO2] increased ragweed pollen production by 131 and 320%, respectively, compared to plants grown at pre- industrial [CO2]. The observed stimulations of pollen production from the pre- industrial [CO2] were due to an increase in the number (at 370 mu mol mol(-1)) and number and size (at 600 mu mol mol(-1)) of floral spikes. Overall, floral weight as a percentage of total plant weight decreased (from 21% to 13%), while investment in pollen increased (from 3.6 to 6%) between 280 and 600 mu mol mol(-1) CO2. Our results suggest that the continuing increase in atmospheric [CO2] could directly influence public health by stimulating the growth and pollen production of allergy- inducing species such as ragweed.. allergens| elevated carbon dioxide| photosynthesis| pollen| relative growth rate|carbon-dioxide| elevated co2| growth-response| atmospheric co2| united-states| enrichment| plants| photosynthesis| weeds.	2000	allergens| elevated carbon dioxide| photosynthesis| pollen| relative growth rate|carbon-dioxide| elevated co2| growth-response| atmospheric co2| united-states| enrichment| plants| photosynthesis| weeds	Ziska, LH; Caulfield, FA	Rising CO2 and pollen production of common ragweed (Ambrosia artemisiifolia), a known allergy-inducing species: implications for public health		AUSTRALIAN JOURNAL OF PLANT PHYSIOLOGY	allergens; elevated carbon dioxide; photosynthesis; pollen; relative growth rate	CARBON-DIOXIDE; ELEVATED CO2; GROWTH-RESPONSE; ATMOSPHERIC CO2; UNITED-STATES; ENRICHMENT; PLANTS; PHOTOSYNTHESIS; WEEDS	Although environmental factors such as precipitation and temperature are recognized as influencing pollen production, the impact of rising atmospheric carbon dioxide concentration ([ CO2]) on the potential growth and pollen production of hay- fever- inducing plants is unknown. Here we present measurements of growth and pollen production of common ragweed (Ambrosia artemisiifolia L.) from pre- industrial [CO2] (280 mu mol mol(-1)) to current concentrations (370 mu mol mol(-1)) to a projected 21st century concentration (600 mu mol mol(-1)). We found that exposure to current and elevated [CO2] increased ragweed pollen production by 131 and 320%, respectively, compared to plants grown at pre- industrial [CO2]. The observed stimulations of pollen production from the pre- industrial [CO2] were due to an increase in the number (at 370 mu mol mol(-1)) and number and size (at 600 mu mol mol(-1)) of floral spikes. Overall, floral weight as a percentage of total plant weight decreased (from 21% to 13%), while investment in pollen increased (from 3.6 to 6%) between 280 and 600 mu mol mol(-1) CO2. Our results suggest that the continuing increase in atmospheric [CO2] could directly influence public health by stimulating the growth and pollen production of allergy- inducing species such as ragweed.	30	112	2000	6		Plant Sciences
IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy. IL-33 is a nuclear cytokine from the IL-1 family constitutively expressed in epithelial barrier tissues and lymphoid organs, which plays important roles in type-2 innate immunity and human asthma. Recent studies indicate that IL-33 induces production of large amounts of IL-5 and IL-13 by group 2 innate lymphoid cells (ILC2s), for initiation of allergic inflammation shortly after exposure to allergens or infection with parasites or viruses. IL-33 appears to function as an alarmin (alarm signal) rapidly released from producing cells upon cellular damage or cellular stress. In this review, we discuss the cellular sources, mode of action and regulation of IL-33, and we highlight its crucial roles in vivo with particular emphasis on results obtained using IL33-deficient mice.. t-cell responses| lymphoid-cells| type-2 immunity| lung inflammation| airway inflammation| endogenous il-33| in-vivo| asthma| expression| association.	DEC-2014	t-cell responses| lymphoid-cells| type-2 immunity| lung inflammation| airway inflammation| endogenous il-33| in-vivo| asthma| expression| association	Cayrol, C; Girard, JP	IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy		CURRENT OPINION IN IMMUNOLOGY		T-CELL RESPONSES; LYMPHOID-CELLS; TYPE-2 IMMUNITY; LUNG INFLAMMATION; AIRWAY INFLAMMATION; ENDOGENOUS IL-33; IN-VIVO; ASTHMA; EXPRESSION; ASSOCIATION	IL-33 is a nuclear cytokine from the IL-1 family constitutively expressed in epithelial barrier tissues and lymphoid organs, which plays important roles in type-2 innate immunity and human asthma. Recent studies indicate that IL-33 induces production of large amounts of IL-5 and IL-13 by group 2 innate lymphoid cells (ILC2s), for initiation of allergic inflammation shortly after exposure to allergens or infection with parasites or viruses. IL-33 appears to function as an alarmin (alarm signal) rapidly released from producing cells upon cellular damage or cellular stress. In this review, we discuss the cellular sources, mode of action and regulation of IL-33, and we highlight its crucial roles in vivo with particular emphasis on results obtained using IL33-deficient mice.	49	111	2014	7	10.1016/j.coi.2014.09.004	Immunology
Molecular diagnosis in allergy. Development and progress made in the field of recombinant allergens have allowed for the development of a new concept in allergy diagnosis, molecular diagnosis (MD), which makes it possible to identify potential disease-eliciting molecules. Microarray-based testing performed with a small amount of serum sample enables clinicians to determine specific-IgE antibodies against multiple recombinants or purified natural allergen components. Performance characteristics of allergens so far tested are comparable with current diagnostic tests, but have to be confirmed in larger studies. The use of allergen components and the successful interpretation of test results in the clinic require some degree of knowledge about the basis of allergen components and their clinical implications. Allergen components can be classified by protein families based on their function and structure. This review provides a brief overview of basic information on allergen components, recombinants or purified, currently available or soon to become commercially available in ImmunoCAP or ISAC (R) systems, including names, protein family and function. Special consideration is given to primary or species-specific sensitization and possible cross-reactivity, because one of the most important clinical utility of MD is its ability to reveal whether the sensitization is genuine in nature (primary, species-specific) or if it is due to cross-reactivity to proteins with similar protein structures, which may help to evaluate the risk of reaction on exposure to different allergen sources. MD can be a support tool for choosing the right treatment for the right patient with the right timing. Such information will eventually give clinicians the possibility to individualize the actions taken, including an advice on targeted allergen exposure reduction, selection of suitable allergens for specific immunotherapy, or the need to perform food challenges. Nevertheless, all in vitro tests should be evaluated together with the clinical history, because allergen sensitization does not necessarily imply clinical responsiveness.. lipid-transfer protein| controlled food challenge| natural-rubber latex| component-resolved diagnosis| exercise-induced anaphylaxis| parietaria-judaica pollen| cows milk allergy| house-dust mite| aspergillus-fumigatus allergens| plantago-lanceolata pollen.	OCT-2010	lipid-transfer protein| controlled food challenge| natural-rubber latex| component-resolved diagnosis| exercise-induced anaphylaxis| parietaria-judaica pollen| cows milk allergy| house-dust mite| aspergillus-fumigatus allergens| plantago-lanceolata pollen	Sastre, J	Molecular diagnosis in allergy		CLINICAL AND EXPERIMENTAL ALLERGY		LIPID-TRANSFER PROTEIN; CONTROLLED FOOD CHALLENGE; NATURAL-RUBBER LATEX; COMPONENT-RESOLVED DIAGNOSIS; EXERCISE-INDUCED ANAPHYLAXIS; PARIETARIA-JUDAICA POLLEN; COWS MILK ALLERGY; HOUSE-DUST MITE; ASPERGILLUS-FUMIGATUS ALLERGENS; PLANTAGO-LANCEOLATA POLLEN	Development and progress made in the field of recombinant allergens have allowed for the development of a new concept in allergy diagnosis, molecular diagnosis (MD), which makes it possible to identify potential disease-eliciting molecules. Microarray-based testing performed with a small amount of serum sample enables clinicians to determine specific-IgE antibodies against multiple recombinants or purified natural allergen components. Performance characteristics of allergens so far tested are comparable with current diagnostic tests, but have to be confirmed in larger studies. The use of allergen components and the successful interpretation of test results in the clinic require some degree of knowledge about the basis of allergen components and their clinical implications. Allergen components can be classified by protein families based on their function and structure. This review provides a brief overview of basic information on allergen components, recombinants or purified, currently available or soon to become commercially available in ImmunoCAP or ISAC (R) systems, including names, protein family and function. Special consideration is given to primary or species-specific sensitization and possible cross-reactivity, because one of the most important clinical utility of MD is its ability to reveal whether the sensitization is genuine in nature (primary, species-specific) or if it is due to cross-reactivity to proteins with similar protein structures, which may help to evaluate the risk of reaction on exposure to different allergen sources. MD can be a support tool for choosing the right treatment for the right patient with the right timing. Such information will eventually give clinicians the possibility to individualize the actions taken, including an advice on targeted allergen exposure reduction, selection of suitable allergens for specific immunotherapy, or the need to perform food challenges. Nevertheless, all in vitro tests should be evaluated together with the clinical history, because allergen sensitization does not necessarily imply clinical responsiveness.	215	111	2010	19	10.1111/j.1365-2222.2010.03585.x	Allergy; Immunology
Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide. Background: Children with severe asthma have persistent symptoms despite treatment with inhaled corticosteroids (ICSs). The differentiating features of severe asthma in children are poorly defined. Objective: To identify features of severe versus mild-to-moderate asthma in school-age children using noninvasive assessments of lung function, atopy, and airway inflammation. Methods: A total of 75 children (median age, 10 years) with asthma underwent baseline characterization including spirometry and lung volume testing, methacholine bronchoprovocation, allergy evaluation, and offline measurement of exhaled nitric oxide (F-ENO). Twenty-eight were followed longitudinally over 6 months. Participants were assigned to the severe asthma subgroup if they required high-dose ICS plus 2 or more minor criteria. Results: Children with severe versus mild-to-moderate asthma had more symptoms, greater airway obstruction, more gas trapping, and increased bronchial responsiveness to methacholine. Subjects with severe asthma also had higher concentrations of F-ENO and significantly greater sensitization to aeroallergens. With long-term study, both the reduction in FEVI and increase in F-ENO persisted in the severe versus mild-to-moderate group. Furthermore, despite adjustments in ICS doses, the frequency of exacerbations was significantly higher in subjects with severe (83%) versus mild-to-moderate asthma (43%). Conclusion: Severe asthma in childhood is characterized by poor symptom control despite high-dose ICS treatment and can be differentiated from mild-to-moderate asthma by measurement of lung function and F-ENO. Clinical implications: Clinicians should suspect severe asthma in children with poor response to ICS, airway obstruction, and high F-ENO.. children| asthma| atopy| nitric oxide| pulmonary function testing|to-treat asthma| childhood asthma| difficult asthma| eosinophilic inflammation| inhaled corticosteroids| airway inflammation| allergen exposure| risk-factors| disparities| population.	DEC-2006	children| asthma| atopy| nitric oxide| pulmonary function testing|to-treat asthma| childhood asthma| difficult asthma| eosinophilic inflammation| inhaled corticosteroids| airway inflammation| allergen exposure| risk-factors| disparities| population	Fitzpatrick, AM; Gaston, BM; Erzurum, SC; Teague, WG	Features of severe asthma in school-age children: Atopy and increased exhaled nitric oxide		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	children; asthma; atopy; nitric oxide; pulmonary function testing	TO-TREAT ASTHMA; CHILDHOOD ASTHMA; DIFFICULT ASTHMA; EOSINOPHILIC INFLAMMATION; INHALED CORTICOSTEROIDS; AIRWAY INFLAMMATION; ALLERGEN EXPOSURE; RISK-FACTORS; DISPARITIES; POPULATION	Background: Children with severe asthma have persistent symptoms despite treatment with inhaled corticosteroids (ICSs). The differentiating features of severe asthma in children are poorly defined. Objective: To identify features of severe versus mild-to-moderate asthma in school-age children using noninvasive assessments of lung function, atopy, and airway inflammation. Methods: A total of 75 children (median age, 10 years) with asthma underwent baseline characterization including spirometry and lung volume testing, methacholine bronchoprovocation, allergy evaluation, and offline measurement of exhaled nitric oxide (F-ENO). Twenty-eight were followed longitudinally over 6 months. Participants were assigned to the severe asthma subgroup if they required high-dose ICS plus 2 or more minor criteria. Results: Children with severe versus mild-to-moderate asthma had more symptoms, greater airway obstruction, more gas trapping, and increased bronchial responsiveness to methacholine. Subjects with severe asthma also had higher concentrations of F-ENO and significantly greater sensitization to aeroallergens. With long-term study, both the reduction in FEVI and increase in F-ENO persisted in the severe versus mild-to-moderate group. Furthermore, despite adjustments in ICS doses, the frequency of exacerbations was significantly higher in subjects with severe (83%) versus mild-to-moderate asthma (43%). Conclusion: Severe asthma in childhood is characterized by poor symptom control despite high-dose ICS treatment and can be differentiated from mild-to-moderate asthma by measurement of lung function and F-ENO. Clinical implications: Clinicians should suspect severe asthma in children with poor response to ICS, airway obstruction, and high F-ENO.	37	111	2006	8	10.1016/j.jaci.2006.08.019	Allergy; Immunology
"Development of an in vitro skin sensitization test using human cell lines; human Cell Line Activation Test (h-CLAT) II. An inter-laboratory study of the h-CLAT. Recent regulatory changes have placed a major emphasis on in vitro, safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled ""optimization of the h-CLAT protocol"" within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24 h and 48 h exposure to six known allergens (e.g., DNCB, pPD, NiSO4) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1x, 0.5x, 1x, and 2x of the 50% inhibitory concentration (IC50)) were evaluated. IC50 was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24 h and a 48 h exposure. We also found that the 24 h treatment time tended to have a better accuracy than the 48 h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24 h and the 48 h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen/non-allergen, especially using THP-1 cells. These results suggest that our method, human Cell Line Activation Test (h-CLAT), using human cell lines THP-1 and U-937, but especially THP-1 cells at 24 h treatment, may be a useful in vitro skin sensitization model to predict various contact allergens. (c) 2005 Elsevier Ltd. All rights reserved.. thp-1| u-937| cd86| cd54| inter laboratory| validation| cell line| in vitro skin sensitization|epidermal langerhans cells| dendritic cells| contact allergens| t-cells| costimulatory molecules| expression| irritants| chemicals| exposure| haptens."	AUG-2006	thp-1| u-937| cd86| cd54| inter laboratory| validation| cell line| in vitro skin sensitization|epidermal langerhans cells| dendritic cells| contact allergens| t-cells| costimulatory molecules| expression| irritants| chemicals| exposure| haptens	Sakaguchi, H; Ashikaga, T; Miyazawa, M; Yoshida, Y; Ito, Y; Yoneyama, K; Hirota, M; Itagaki, H; Toyoda, H; Suzuki, H	Development of an in vitro skin sensitization test using human cell lines; human Cell Line Activation Test (h-CLAT) II. An inter-laboratory study of the h-CLAT		TOXICOLOGY IN VITRO	THP-1; U-937; CD86; CD54; inter laboratory; validation; cell line; in vitro skin sensitization	EPIDERMAL LANGERHANS CELLS; DENDRITIC CELLS; CONTACT ALLERGENS; T-CELLS; COSTIMULATORY MOLECULES; EXPRESSION; IRRITANTS; CHEMICALS; EXPOSURE; HAPTENS	"Recent regulatory changes have placed a major emphasis on in vitro, safety testing and alternative models. In regard to skin sensitization tests, dendritic cells (DCs) derived from human peripheral blood have been considered in the development of new in vitro alternatives. Human cell lines have been also reported recently. In our previous study, we suggested that measuring CD86 and/or CD54 expression on THP-1 cells (human monocytic leukemia cell line) could be used as an in vitro skin sensitization method. An inter-laboratory study among two laboratories was undertaken in Japan in order to further develop an in vitro skin sensitization model. In the present study, we used two human cell lines: THP-1 and U-937 (human histiocytic lymphoma cell line). First we optimized our test protocol (refer to the related paper entitled ""optimization of the h-CLAT protocol"" within this journal) and then we did an inter-laboratory validation with nine chemicals using the optimized protocol. We measured the expression of CD86 and CD54 on the above cells using flow cytometry after a 24 h and 48 h exposure to six known allergens (e.g., DNCB, pPD, NiSO4) and three non-allergens (e.g., SLS, tween 80). For the sample test concentration, four doses (0.1x, 0.5x, 1x, and 2x of the 50% inhibitory concentration (IC50)) were evaluated. IC50 was calculated using MTT assay. We found that allergens/non-allergens were better predicted using THP-1 cells compared to U-937 cells following a 24 h and a 48 h exposure. We also found that the 24 h treatment time tended to have a better accuracy than the 48 h treatment time for THP-1 cells. Expression of CD86 and CD54 were good predictive markers for THP-1 cells, but for U-937 cells, expression of CD86 was a better predictor than CD54, at the 24 h and the 48 h treatment time. The accuracy also improved when both markers (CD86 and CD54) were used as compared with a single marker for THP-1 cells. Both laboratories gave a good prediction of allergen/non-allergen, especially using THP-1 cells. These results suggest that our method, human Cell Line Activation Test (h-CLAT), using human cell lines THP-1 and U-937, but especially THP-1 cells at 24 h treatment, may be a useful in vitro skin sensitization model to predict various contact allergens. (c) 2005 Elsevier Ltd. All rights reserved."	26	111	2006	11	10.1016/j.tiv.2005.10.014	Toxicology
Maternal smoking during pregnancy increases the risk of recurrent wheezing during the first years of life (BAMSE). Background: Exposure to cigarette smoking during foetal and early postnatal life may have implications for lung health. The aim of this study was to assess the possible effects of such exposure in utero on lower respiratory disease in children up to two years of age. Methods: A birth cohort of 4089 newborn infants was followed for two years using parental questionnaires. When the infant was two months old the parents completed a questionnaire on various lifestyle factors, including maternal smoking during pregnancy and after birth. At one and two years of age information was obtained by questionnaire on symptoms of allergic and respiratory diseases as well as on environmental exposures, particularly exposure to environmental tobacco smoke (ETS). Adjustments were made for potential confounders. Results: When the mother had smoked during pregnancy but not after that, there was an increased risk of recurrent wheezing up to two years' age, ORadj = 2.2, (95% CI 1.3-3.6). The corresponding OR was 1.6, ( 95% CI 1.2-2.3) for reported exposure to ETS with or without maternal smoking in utero. Maternal smoking during pregnancy but no exposure to ETS also increased the risk of doctor's diagnosed asthma up to two years of age, ORadj = 2.1, ( 95% CI 1.2-3.7). Conclusion: Exposure to maternal cigarette smoking in utero is a risk factor for recurrent wheezing, as well as doctor's diagnosed asthma in children up to two years of age.. environmental tobacco-smoke| childhood lung-function| respiratory-function| in-utero| parental smoking| passive smoking| asthma| exposure| children| bronchitis.	JAN 5-2006	environmental tobacco-smoke| childhood lung-function| respiratory-function| in-utero| parental smoking| passive smoking| asthma| exposure| children| bronchitis	Lannero, E; Wickman, M; Pershagen, G; Nordvall, L	Maternal smoking during pregnancy increases the risk of recurrent wheezing during the first years of life (BAMSE)		RESPIRATORY RESEARCH		ENVIRONMENTAL TOBACCO-SMOKE; CHILDHOOD LUNG-FUNCTION; RESPIRATORY-FUNCTION; IN-UTERO; PARENTAL SMOKING; PASSIVE SMOKING; ASTHMA; EXPOSURE; CHILDREN; BRONCHITIS	Background: Exposure to cigarette smoking during foetal and early postnatal life may have implications for lung health. The aim of this study was to assess the possible effects of such exposure in utero on lower respiratory disease in children up to two years of age. Methods: A birth cohort of 4089 newborn infants was followed for two years using parental questionnaires. When the infant was two months old the parents completed a questionnaire on various lifestyle factors, including maternal smoking during pregnancy and after birth. At one and two years of age information was obtained by questionnaire on symptoms of allergic and respiratory diseases as well as on environmental exposures, particularly exposure to environmental tobacco smoke (ETS). Adjustments were made for potential confounders. Results: When the mother had smoked during pregnancy but not after that, there was an increased risk of recurrent wheezing up to two years' age, ORadj = 2.2, (95% CI 1.3-3.6). The corresponding OR was 1.6, ( 95% CI 1.2-2.3) for reported exposure to ETS with or without maternal smoking in utero. Maternal smoking during pregnancy but no exposure to ETS also increased the risk of doctor's diagnosed asthma up to two years of age, ORadj = 2.1, ( 95% CI 1.2-3.7). Conclusion: Exposure to maternal cigarette smoking in utero is a risk factor for recurrent wheezing, as well as doctor's diagnosed asthma in children up to two years of age.	26	111	2006	6	10.1186/1465-9921-7-3	Respiratory System
The safety and efficacy of inhaled dry powder mannitol as a bronchial provocation test for airway hyperresponsiveness: a phase 3 comparison study with hypertonic (4.5%) saline. Background: Inhaled mannitol is a new bronchial provocation test (BPT) developed to improve portability and standardisation of osmotic challenge testing. Osmotic challenge tests have an advantage over the traditional methods of measuring airway hyperresponsiveness using methacholine as they demonstrate higher specificity to identify asthma and thus the need for treatment with inhaled corticosteroids (ICS). The safety and the efficacy of mannitol (M) as a BPT to measure airway hyperresponsiveness were compared to hypertonic (4.5%) saline (HS) in people both with and without signs and symptoms of asthma. Methods: A phase III, multi-centre, open label, operator-blinded, crossover design, randomised trial, with follow-up. Asthmatics and non-asthmatics (6-83 yr) were recruited and 592 subjects completed the study. Mannitol was delivered using a low resistance dry powder inhaler and HS was delivered using an ultrasonic nebuliser. The FEV1 was measured 60 seconds after each dose of mannitol (5,10,20,40,80,160,160,160 mg) and after each exposure to HS (0.5,1.0,2.0,4.0,8.0 minutes). A 15% fall in FEV1 defined a positive test. Adverse events were monitored and diaries kept for 7 days following the tests. Results: Mean pre-test FEV1 (mean +/- SD) was 95.5 +/- 14% predicted. 296 were positive to mannitol (M+) and 322 positive to HS (HS+). A post study physician conducted clinical assessment identified 82.3% asthmatic (44% classified mild) and 17.7% non-asthmatic. Of those M+, 70.1% were taking ICS and of those mannitol negative (M-), 81.1% were taking ICS. The % fall in FEV1 for mannitol in asthmatics was 21.0% +/- 5.7 and for the non-asthmatics, 5.5% +/- 4.8. The median PD15 M was 148 mg and PD15 HS 6.2 ml. The sensitivity of M to identify HS+ was 80.7% and the specificity 86.7%. The sensitivity of M compared with the clinical assessment was 59.8% and specificity 95.2% and increased to 88.7% and 95.0% respectively when the M- subjects taking ICS were excluded. Cough was common during testing. There were no serious adverse events. The diarised events were similar for mannitol and HS, the most common being headache (17.2% M, 19% HS), pharyngolaryngeal pain (5.1% M, 3% HS), nausea (4.3% M, 3% HS), and cough (2.2% M, 2.4% HS). Conclusion: The efficacy and safety of mannitol was demonstrated in non-asthmatic and clinically diagnosed asthmatic adults and children.. asthmatic subjects| induced bronchoconstriction| epidemiologic survey| challenge| responsiveness| exercise| children| methacholine| sensitivity| hyperventilation.	DEC 9-2005	asthmatic subjects| induced bronchoconstriction| epidemiologic survey| challenge| responsiveness| exercise| children| methacholine| sensitivity| hyperventilation	Brannan, JD; Anderson, SD; Perry, CP; Freed-Martens, R; Lassig, AR; Charlton, B	The safety and efficacy of inhaled dry powder mannitol as a bronchial provocation test for airway hyperresponsiveness: a phase 3 comparison study with hypertonic (4.5%) saline		RESPIRATORY RESEARCH		ASTHMATIC SUBJECTS; INDUCED BRONCHOCONSTRICTION; EPIDEMIOLOGIC SURVEY; CHALLENGE; RESPONSIVENESS; EXERCISE; CHILDREN; METHACHOLINE; SENSITIVITY; HYPERVENTILATION	Background: Inhaled mannitol is a new bronchial provocation test (BPT) developed to improve portability and standardisation of osmotic challenge testing. Osmotic challenge tests have an advantage over the traditional methods of measuring airway hyperresponsiveness using methacholine as they demonstrate higher specificity to identify asthma and thus the need for treatment with inhaled corticosteroids (ICS). The safety and the efficacy of mannitol (M) as a BPT to measure airway hyperresponsiveness were compared to hypertonic (4.5%) saline (HS) in people both with and without signs and symptoms of asthma. Methods: A phase III, multi-centre, open label, operator-blinded, crossover design, randomised trial, with follow-up. Asthmatics and non-asthmatics (6-83 yr) were recruited and 592 subjects completed the study. Mannitol was delivered using a low resistance dry powder inhaler and HS was delivered using an ultrasonic nebuliser. The FEV1 was measured 60 seconds after each dose of mannitol (5,10,20,40,80,160,160,160 mg) and after each exposure to HS (0.5,1.0,2.0,4.0,8.0 minutes). A 15% fall in FEV1 defined a positive test. Adverse events were monitored and diaries kept for 7 days following the tests. Results: Mean pre-test FEV1 (mean +/- SD) was 95.5 +/- 14% predicted. 296 were positive to mannitol (M+) and 322 positive to HS (HS+). A post study physician conducted clinical assessment identified 82.3% asthmatic (44% classified mild) and 17.7% non-asthmatic. Of those M+, 70.1% were taking ICS and of those mannitol negative (M-), 81.1% were taking ICS. The % fall in FEV1 for mannitol in asthmatics was 21.0% +/- 5.7 and for the non-asthmatics, 5.5% +/- 4.8. The median PD15 M was 148 mg and PD15 HS 6.2 ml. The sensitivity of M to identify HS+ was 80.7% and the specificity 86.7%. The sensitivity of M compared with the clinical assessment was 59.8% and specificity 95.2% and increased to 88.7% and 95.0% respectively when the M- subjects taking ICS were excluded. Cough was common during testing. There were no serious adverse events. The diarised events were similar for mannitol and HS, the most common being headache (17.2% M, 19% HS), pharyngolaryngeal pain (5.1% M, 3% HS), nausea (4.3% M, 3% HS), and cough (2.2% M, 2.4% HS). Conclusion: The efficacy and safety of mannitol was demonstrated in non-asthmatic and clinically diagnosed asthmatic adults and children.	32	111	2005	12	10.1186/1465-9921-6-144	Respiratory System
Inhaled p38 alpha mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. The p38 mitogen-activated protein kinase (MAPK) plays a critical role in the activation of inflammatory cells. Therefore, we investigated the antiinflammatory effects of a respirable p38 alpha MAPK antisense oligonucleotide (p38 alpha-ASO) in a mouse asthma model. A potent and selective p38 alpha-ASO was characterized in vitro. Inhalation of aerosolized p38 alpha-ASO using an aerosol chamber dosing system produced measurable lung deposition of ASO and significant reduction of ovalbumin (OVA-)-induced increases in total cells, eosinophils, and interleukin 4 (IL-4), IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and dose-dependent inhibition of airway hyperresponsiveness in allergen-challenged mice. Furthermore, inhaled p38 alpha-ASO markedly inhibited OVA-induced lung tissue eosinophilia and airway mucus hypersecretion. Quantitative polymerase chain reaction analysis of bronchoalveolar lavage fluid cells and peribronchial lymph node cells showed that p38 alpha-ASO significantly reduced p38 alpha MAPK mRNA expression. Nose-only aerosol exposure of mice verified the p38 alpha-ASO-induced inhibition of OVA-induced pulmonary eosinophilia, mucus hypersecretion, and airway hyperresponsiveness. None of the effects of the p38 alpha-ASO were produced by a six-base mismatched control oligonucleotide. These findings demonstrate antisense pharmacodynamic activity in the airways after aerosol delivery and suggest that a p38 alpha MAPK ASO approach may have therapeutic potential for asthma and other inflammatory lung diseases.. asthma| bronchoalveolar lavage fluid| eosinophilia| mucus hypersecretion| ovalbumin|airway smooth-muscle| cytokine production| signaling pathways| t-cells| antigen-receptor| epithelial-cells| map kinase| mast-cell| expression| inhibitor.	MAR 15-2005	asthma| bronchoalveolar lavage fluid| eosinophilia| mucus hypersecretion| ovalbumin|airway smooth-muscle| cytokine production| signaling pathways| t-cells| antigen-receptor| epithelial-cells| map kinase| mast-cell| expression| inhibitor	Duan, W; Chan, JHP; Mckay, K; Crosby, JR; Choo, HH; Leung, BP; Karras, JG; Wong, WSF	Inhaled p38 alpha mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; bronchoalveolar lavage fluid; eosinophilia; mucus hypersecretion; ovalbumin	AIRWAY SMOOTH-MUSCLE; CYTOKINE PRODUCTION; SIGNALING PATHWAYS; T-CELLS; ANTIGEN-RECEPTOR; EPITHELIAL-CELLS; MAP KINASE; MAST-CELL; EXPRESSION; INHIBITOR	The p38 mitogen-activated protein kinase (MAPK) plays a critical role in the activation of inflammatory cells. Therefore, we investigated the antiinflammatory effects of a respirable p38 alpha MAPK antisense oligonucleotide (p38 alpha-ASO) in a mouse asthma model. A potent and selective p38 alpha-ASO was characterized in vitro. Inhalation of aerosolized p38 alpha-ASO using an aerosol chamber dosing system produced measurable lung deposition of ASO and significant reduction of ovalbumin (OVA-)-induced increases in total cells, eosinophils, and interleukin 4 (IL-4), IL-5, and IL-13 levels in bronchoalveolar lavage fluid, and dose-dependent inhibition of airway hyperresponsiveness in allergen-challenged mice. Furthermore, inhaled p38 alpha-ASO markedly inhibited OVA-induced lung tissue eosinophilia and airway mucus hypersecretion. Quantitative polymerase chain reaction analysis of bronchoalveolar lavage fluid cells and peribronchial lymph node cells showed that p38 alpha-ASO significantly reduced p38 alpha MAPK mRNA expression. Nose-only aerosol exposure of mice verified the p38 alpha-ASO-induced inhibition of OVA-induced pulmonary eosinophilia, mucus hypersecretion, and airway hyperresponsiveness. None of the effects of the p38 alpha-ASO were produced by a six-base mismatched control oligonucleotide. These findings demonstrate antisense pharmacodynamic activity in the airways after aerosol delivery and suggest that a p38 alpha MAPK ASO approach may have therapeutic potential for asthma and other inflammatory lung diseases.	49	111	2005	8	10.1164/rccm.200408	General & Internal Medicine; Respiratory System
Allergic rhinitis and asthma comorbidity in a survey of young adults in Italy. Background: Several studies have provided evidence of a strong association between asthma and allergic or nonallergic rhinitis, leading to the hypothesis that allergic rhinitis (AR) and asthma represent a continuum of the same disease. Aim: The aims of our study were: (i) to measure the comorbidity of AR and asthma and asthma-like symptoms and (ii) to assess whether asthma, AR, and their coexistence share a common pattern of individual risk factors. Methods: The subjects are participants from the Italian multicentre, cross-sectional survey on respiratory symptoms in the young adult general population (Italian Study of Asthma in Young Adults, ISAYA). The relationship between individual risk factors and asthma, AR and their coexistence, was studied by means of a multinomial logistic regression. Results: About 60% of asthmatics reported AR. On the other hand, subjects with AR presented an eightfold risk of having asthma compared to subjects without AR. Age was negatively associated with asthma [OR = 0.89, 95% confidence interval (CI): 0.82-0.96], AR (OR = 0.92, 95% CI: 0.86-0.98), and asthma associated with AR (OR = 0.83, 95% CI: 0.79-0.88). The risk of AR without asthma was significantly higher in the upper social classes (OR = 1.23, 95% CI: 1.08-1.39). Active current smoking exposure was positively associated with asthma alone (OR = 1.24, 95% CI: 1.09-1.41) and negatively associated with AR with (OR = 0.69, 95% CI: 0.54-0.88) or without (OR = 0.76, 95% CI: 0.69-0.84) asthma. Conclusions: Asthma and AR coexist in a substantial percentage of patients; bronchial asthma and AR, when associated, seem to share the same risk factors as AR alone while asthma without AR seems to be a different condition, at least with respect to some relevant risk factors.. allergic rhinitis| asthma| comorbidity| epidemiology|respiratory health survey| natural-history| air-pollution| risk-factors| prevalence| community| symptoms| epidemiology| lung| questionnaire.	FEB-2005	allergic rhinitis| asthma| comorbidity| epidemiology|respiratory health survey| natural-history| air-pollution| risk-factors| prevalence| community| symptoms| epidemiology| lung| questionnaire	Bugiani, M; Carosso, A; Migliore, E; Piccioni, P; Corsico, A; Olivieri, M; Ferrari, M; Pirina, P; de Marco, R	Allergic rhinitis and asthma comorbidity in a survey of young adults in Italy		ALLERGY	allergic rhinitis; asthma; comorbidity; epidemiology	RESPIRATORY HEALTH SURVEY; NATURAL-HISTORY; AIR-POLLUTION; RISK-FACTORS; PREVALENCE; COMMUNITY; SYMPTOMS; EPIDEMIOLOGY; LUNG; QUESTIONNAIRE	Background: Several studies have provided evidence of a strong association between asthma and allergic or nonallergic rhinitis, leading to the hypothesis that allergic rhinitis (AR) and asthma represent a continuum of the same disease. Aim: The aims of our study were: (i) to measure the comorbidity of AR and asthma and asthma-like symptoms and (ii) to assess whether asthma, AR, and their coexistence share a common pattern of individual risk factors. Methods: The subjects are participants from the Italian multicentre, cross-sectional survey on respiratory symptoms in the young adult general population (Italian Study of Asthma in Young Adults, ISAYA). The relationship between individual risk factors and asthma, AR and their coexistence, was studied by means of a multinomial logistic regression. Results: About 60% of asthmatics reported AR. On the other hand, subjects with AR presented an eightfold risk of having asthma compared to subjects without AR. Age was negatively associated with asthma [OR = 0.89, 95% confidence interval (CI): 0.82-0.96], AR (OR = 0.92, 95% CI: 0.86-0.98), and asthma associated with AR (OR = 0.83, 95% CI: 0.79-0.88). The risk of AR without asthma was significantly higher in the upper social classes (OR = 1.23, 95% CI: 1.08-1.39). Active current smoking exposure was positively associated with asthma alone (OR = 1.24, 95% CI: 1.09-1.41) and negatively associated with AR with (OR = 0.69, 95% CI: 0.54-0.88) or without (OR = 0.76, 95% CI: 0.69-0.84) asthma. Conclusions: Asthma and AR coexist in a substantial percentage of patients; bronchial asthma and AR, when associated, seem to share the same risk factors as AR alone while asthma without AR seems to be a different condition, at least with respect to some relevant risk factors.	45	111	2005	6	10.1111/j.1398-9995.2005.00659.x	Allergy; Immunology
Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens. Background Mites belong to the most frequent and potent allergen sources. Immunotherapy with mite allergen extracts is frequently performed if allergen avoidance is not possible or successful. However, highly controversial results have been reported for mite-specific immunotherapy. Objective The aim of this study was to develop diagnostic concepts that may contribute to an improved selection of patients for immunotherapy with Der p allergen extracts and that may be used for immunological monitoring of patients undergoing this treatment. Methods The IgE reactivity profiles to Der p extract were determined in a Middle European mite-allergic population by IgE immunoblotting and by using a panel of seven purified natural or recombinant Der p allergens (nDer p 1, nDer p 4, rDer p 2, rDer p 5, rDer p 7, rDer p 8, rDer p 10). Furthermore, we investigated the sensitization and cross-reactivity to house-dust- and storage-mite allergen extracts by CAP FEIA measurements and by IgE competition studies. Results More than 95% of the patients could be diagnosed with a combination of nDer p 1 and rDer p 2. With the methods used, we could discriminate mite-allergic patients who were mainly sensitized to the major Der p allergens (Der p 1, Der p 2) from patients with a broad sensitization profile, including highly cross-reactive allergens (e.g. Der p 10: tropomyosin) as well as reactivity to storage mites. Conclusions Diagnostic tests containing the major mite allergens (i.e. Der p 1, Der p 2) and highly cross-reactive mite allergens (e.g. Der p 10) may improve the diagnostic selection of patients for immunotherapy with Der p extracts. These tests may also be used for the immunological monitoring of patients undergoing immunotherapy.. cross-reactivity| diagnosis| house-dust mites| ige reactivity profile| immunotherapy| natural and recombinant allergens|dermatophagoides-pteronyssinus allergen| der-p-i| standardized extracts| cross-reactivity| human ige| immunotherapy| binding| asthma| children| pollen.	APR-2004	cross-reactivity| diagnosis| house-dust mites| ige reactivity profile| immunotherapy| natural and recombinant allergens|dermatophagoides-pteronyssinus allergen| der-p-i| standardized extracts| cross-reactivity| human ige| immunotherapy| binding| asthma| children| pollen	Pittner, G; Vrtala, S; Thomas, WR; Weghofer, M; Kundi, M; Horak, F; Kraft, D; Valenta, R	Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens		CLINICAL AND EXPERIMENTAL ALLERGY	cross-reactivity; diagnosis; house-dust mites; IgE reactivity profile; immunotherapy; natural and recombinant allergens	DERMATOPHAGOIDES-PTERONYSSINUS ALLERGEN; DER-P-I; STANDARDIZED EXTRACTS; CROSS-REACTIVITY; HUMAN IGE; IMMUNOTHERAPY; BINDING; ASTHMA; CHILDREN; POLLEN	Background Mites belong to the most frequent and potent allergen sources. Immunotherapy with mite allergen extracts is frequently performed if allergen avoidance is not possible or successful. However, highly controversial results have been reported for mite-specific immunotherapy. Objective The aim of this study was to develop diagnostic concepts that may contribute to an improved selection of patients for immunotherapy with Der p allergen extracts and that may be used for immunological monitoring of patients undergoing this treatment. Methods The IgE reactivity profiles to Der p extract were determined in a Middle European mite-allergic population by IgE immunoblotting and by using a panel of seven purified natural or recombinant Der p allergens (nDer p 1, nDer p 4, rDer p 2, rDer p 5, rDer p 7, rDer p 8, rDer p 10). Furthermore, we investigated the sensitization and cross-reactivity to house-dust- and storage-mite allergen extracts by CAP FEIA measurements and by IgE competition studies. Results More than 95% of the patients could be diagnosed with a combination of nDer p 1 and rDer p 2. With the methods used, we could discriminate mite-allergic patients who were mainly sensitized to the major Der p allergens (Der p 1, Der p 2) from patients with a broad sensitization profile, including highly cross-reactive allergens (e.g. Der p 10: tropomyosin) as well as reactivity to storage mites. Conclusions Diagnostic tests containing the major mite allergens (i.e. Der p 1, Der p 2) and highly cross-reactive mite allergens (e.g. Der p 10) may improve the diagnostic selection of patients for immunotherapy with Der p extracts. These tests may also be used for the immunological monitoring of patients undergoing immunotherapy.	36	111	2004	7	10.1111/j.1365-2222.2004.1930.x	Allergy; Immunology
Prevalence and risk factors of asthma and wheezing among US adults: an analysis of the NHANES III data. The prevalence of asthma has been on the increase in the USA and worldwide. To understand the worsening epidemiological trends of asthma, this study analysed the data from the third National Health and Nutrition Examination Survey (NHANES III) to determine the prevalence and risk factors for asthma and wheezing among US adults. This analysis used data from, 18,825 US adults aged greater than or equal to 20 yrs who had participated in the NHANES III project. After excluding subjects with physician-diagnosed emphysema, a total of 18,393 subjects were included in the final analysis. The prevalence of current asthma (asthma) was 4.5% and the prevalence of wheezing in the previous 12 months (wheezing) was 16.4%. Mexican-Americans exhibited the lowest prevalence of asthma when compared with other race/ethnic groups. Multiple logistic regression analysis showed that Mexican-Americans were less likely to report asthma when compared to non-Hispanic whites. Low education level, female sex, current and past smoking status, pet ownership, lifetime diagnosis of physician-diagnosed hay fever and obesity were all significantly associated with asthma and/or wheezing. No significant effect of indoor air pollutants, as derived from the use of household heating/cooking appliances, on asthma and wheezing was observed in this study. In conclusion, this study observed racial/ethnic differences in the prevalence of asthma and wheezing and identified several important risk factors that may contribute to development and/or exacerbation of asthma and wheezing. Contrary to earlier reports, the proxy measures of indoor air pollution used in this study were not found to be associated with increased risk of asthma and wheezing.. asthma| epidemiology| national health and nutrition examination| survey iii|nutrition examination survey| respiratory health survey| 2nd national-health| body-mass index| young-adults| symptoms questionnaire| socioeconomic-status| childhood asthma| reported asthma| puerto-rican.	MAY-2003	asthma| epidemiology| national health and nutrition examination| survey iii|nutrition examination survey| respiratory health survey| 2nd national-health| body-mass index| young-adults| symptoms questionnaire| socioeconomic-status| childhood asthma| reported asthma| puerto-rican	Arif, AA; Delclos, GL; Lee, ES; Tortolero, SR; Whitehead, LW	Prevalence and risk factors of asthma and wheezing among US adults: an analysis of the NHANES III data		EUROPEAN RESPIRATORY JOURNAL	asthma; epidemiology; National Health and Nutrition Examination; Survey III	NUTRITION EXAMINATION SURVEY; RESPIRATORY HEALTH SURVEY; 2ND NATIONAL-HEALTH; BODY-MASS INDEX; YOUNG-ADULTS; SYMPTOMS QUESTIONNAIRE; SOCIOECONOMIC-STATUS; CHILDHOOD ASTHMA; REPORTED ASTHMA; PUERTO-RICAN	The prevalence of asthma has been on the increase in the USA and worldwide. To understand the worsening epidemiological trends of asthma, this study analysed the data from the third National Health and Nutrition Examination Survey (NHANES III) to determine the prevalence and risk factors for asthma and wheezing among US adults. This analysis used data from, 18,825 US adults aged greater than or equal to 20 yrs who had participated in the NHANES III project. After excluding subjects with physician-diagnosed emphysema, a total of 18,393 subjects were included in the final analysis. The prevalence of current asthma (asthma) was 4.5% and the prevalence of wheezing in the previous 12 months (wheezing) was 16.4%. Mexican-Americans exhibited the lowest prevalence of asthma when compared with other race/ethnic groups. Multiple logistic regression analysis showed that Mexican-Americans were less likely to report asthma when compared to non-Hispanic whites. Low education level, female sex, current and past smoking status, pet ownership, lifetime diagnosis of physician-diagnosed hay fever and obesity were all significantly associated with asthma and/or wheezing. No significant effect of indoor air pollutants, as derived from the use of household heating/cooking appliances, on asthma and wheezing was observed in this study. In conclusion, this study observed racial/ethnic differences in the prevalence of asthma and wheezing and identified several important risk factors that may contribute to development and/or exacerbation of asthma and wheezing. Contrary to earlier reports, the proxy measures of indoor air pollution used in this study were not found to be associated with increased risk of asthma and wheezing.	35	111	2003	7	10.1183/09031936.03.00054103	Respiratory System
Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages. It has been proposed that oxidant stress of cells in the lung is one of the underlying mechanisms of particulate pollution-induced exacerbation of lung disease. Individuals who are considered most sensitive to particulate pollution are those with pre-existing airways inflammation, such as chronic obstructive pulmonary disease (COPD), lung infection or asthma. These diseases are characterized by a presence of inflammatory cells in the airways including neutrophils (PMN), eosinophils and monocytes (Mo), and increased numbers of alveolar macrophages (AM). These cells have a high capacity for production of oxygen radicals, as compared to other cell types of the lung. To assess the oxidative response of these various cell types to pollution particles of various sources, luminol-dependent chemiluminescence was employed. Particles including transition metal-rich residual oil fly ashes (ROFAs), coal fly ashes, diesel, SiO2, TiO2 and fugitive dusts were co-cultured with AM, Mo and PMN in a dose range of 10-100 mug/2x 10(5) cells and chemiluminescence determined following a 20-min interaction. A strong oxidant response of AM was restricted to oil fly ashes, while the PMN were most reactive to the dusts containing aluminium silicate. In general, the Mo response was less vigorous, but overlapped both AM- and PMN-stimulating dusts. However, in response to SiO2, and volcanic ash the Mo chemiluminescence exceeded that of the other cell types. Oxygen radicals generated in response to ROFA by the AM were likely to be dependent on mitochondrial processes, while the response in PMN involved the membrane NADPH oxidase complex, as determined by targeting inhibitors. The response of AM to SiO2 of various sizes and TiO2 in the fine size range obtained from different commercial sources, was highly variable, implying that composition rather than size was responsible for the oxidant response. A strong chemiluminescence response was not consistently associated with cytotoxicity in the responsive cell. Taken together, these results suggest that oxidant activation by various sources of particulate matter is cell specific. Therefore, the inflamed lung is likely to be more susceptible to harm of ambient air particulates because of the oxidant stress posed by a broader range of particles. (C), 2002 Published by Elsevier Science Ltd.. oxidant stress| human alveolar macrophages| monocytes| granulocytes| environmental pollution| particles| induced apoptosis| necrosis|oil fly-ash| reactive oxygen metabolites| hydrogen-peroxide| radical generation| induced activation| induced apoptosis| mineral dusts| ambient air| metal-ions| particles.	JUN-2002	oxidant stress| human alveolar macrophages| monocytes| granulocytes| environmental pollution| particles| induced apoptosis| necrosis|oil fly-ash| reactive oxygen metabolites| hydrogen-peroxide| radical generation| induced activation| induced apoptosis| mineral dusts| ambient air| metal-ions| particles	Becker, S; Soukup, JM; Gallagher, JE	Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages		TOXICOLOGY IN VITRO	oxidant stress; human alveolar macrophages; monocytes; granulocytes; environmental pollution; particles; induced apoptosis; necrosis	OIL FLY-ASH; REACTIVE OXYGEN METABOLITES; HYDROGEN-PEROXIDE; RADICAL GENERATION; INDUCED ACTIVATION; INDUCED APOPTOSIS; MINERAL DUSTS; AMBIENT AIR; METAL-IONS; PARTICLES	It has been proposed that oxidant stress of cells in the lung is one of the underlying mechanisms of particulate pollution-induced exacerbation of lung disease. Individuals who are considered most sensitive to particulate pollution are those with pre-existing airways inflammation, such as chronic obstructive pulmonary disease (COPD), lung infection or asthma. These diseases are characterized by a presence of inflammatory cells in the airways including neutrophils (PMN), eosinophils and monocytes (Mo), and increased numbers of alveolar macrophages (AM). These cells have a high capacity for production of oxygen radicals, as compared to other cell types of the lung. To assess the oxidative response of these various cell types to pollution particles of various sources, luminol-dependent chemiluminescence was employed. Particles including transition metal-rich residual oil fly ashes (ROFAs), coal fly ashes, diesel, SiO2, TiO2 and fugitive dusts were co-cultured with AM, Mo and PMN in a dose range of 10-100 mug/2x 10(5) cells and chemiluminescence determined following a 20-min interaction. A strong oxidant response of AM was restricted to oil fly ashes, while the PMN were most reactive to the dusts containing aluminium silicate. In general, the Mo response was less vigorous, but overlapped both AM- and PMN-stimulating dusts. However, in response to SiO2, and volcanic ash the Mo chemiluminescence exceeded that of the other cell types. Oxygen radicals generated in response to ROFA by the AM were likely to be dependent on mitochondrial processes, while the response in PMN involved the membrane NADPH oxidase complex, as determined by targeting inhibitors. The response of AM to SiO2 of various sizes and TiO2 in the fine size range obtained from different commercial sources, was highly variable, implying that composition rather than size was responsible for the oxidant response. A strong chemiluminescence response was not consistently associated with cytotoxicity in the responsive cell. Taken together, these results suggest that oxidant activation by various sources of particulate matter is cell specific. Therefore, the inflamed lung is likely to be more susceptible to harm of ambient air particulates because of the oxidant stress posed by a broader range of particles. (C), 2002 Published by Elsevier Science Ltd.	44	111	2002	10	10.1016/S0887-2333(02)00015-2	Toxicology
Childhood risk factors for atopy and the importance of early intervention. The increasing prevalence of atopic diseases, particularly atopy-associated asthma, has become a major challenge for allergists and public health authorities in many countries. The understanding of the natural history of the atopic march, including the determinants that are modifiable and might become candidates for preventive intervention, is still very limited, Information provided by cross-sectional studies can only generate hypotheses, which need to be supported by prospective, longitudinal, cohort studies. Ultimately, it will depend on the results of well-controlled intervention studies to identify which nutritional, environmental, or lifestyle-related factors should be considered for early intervention and might be useful to reverse the epidemiologic trend.. atopy| prediction| prevention| epidemiology| atopic march| asthma|interferon-gamma production| blood mononuclear-cells| house-dust mite| allergic sensitization| inhalant allergens| domestic exposure| maternal smoking| parental smoking| food allergy| hay-fever.	APR-2001	atopy| prediction| prevention| epidemiology| atopic march| asthma|interferon-gamma production| blood mononuclear-cells| house-dust mite| allergic sensitization| inhalant allergens| domestic exposure| maternal smoking| parental smoking| food allergy| hay-fever	Wahn, U; von Mutius, E	Childhood risk factors for atopy and the importance of early intervention		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopy; prediction; prevention; epidemiology; atopic march; asthma	INTERFERON-GAMMA PRODUCTION; BLOOD MONONUCLEAR-CELLS; HOUSE-DUST MITE; ALLERGIC SENSITIZATION; INHALANT ALLERGENS; DOMESTIC EXPOSURE; MATERNAL SMOKING; PARENTAL SMOKING; FOOD ALLERGY; HAY-FEVER	The increasing prevalence of atopic diseases, particularly atopy-associated asthma, has become a major challenge for allergists and public health authorities in many countries. The understanding of the natural history of the atopic march, including the determinants that are modifiable and might become candidates for preventive intervention, is still very limited, Information provided by cross-sectional studies can only generate hypotheses, which need to be supported by prospective, longitudinal, cohort studies. Ultimately, it will depend on the results of well-controlled intervention studies to identify which nutritional, environmental, or lifestyle-related factors should be considered for early intervention and might be useful to reverse the epidemiologic trend.	79	111	2001	8	10.1067/mai.2001.112943	Allergy; Immunology
Longitudinal study of dust and airborne endotoxin in the home. To characterize the seasonal variability of endotoxin levels, we measured endotoxin in dust from the bed, bedroom floor, and kitchen floor in 20 homes, and in air from the bedroom in 15 of the homes. All homes were located in the greater Boston, Massachusetts, area and were sampled each month from April 1995 to June 1996. Outdoor air was collected at two locations. We found greater within-home than between-home variance for bedroom floor, kitchen floor, and airborne endotoxin. However, the reverse was true for bed dust endotoxin. Thus, studies using single measurements of dust endotoxin are most likely to reliably distinguish between homes if bed dust is sampled. Dust endotoxin levels were not significantly associated with airborne endotoxin. Airborne endotoxin was significantly (p = 0.04) and positively associated with absolute humidity in a mixed-effect model adjusting for a random home effect and fixed effect of sampling month and home characteristics. This finding implies that indoor humidity may be an important factor controlling endotoxin exposure. We found a significant (p < 0.05) seasonal effect in kitchen door dust (spring > fall) and bedroom airborne endotoxin (spring > winter), but not in the other indoor samples. We found significant seasonal pattern in outdoor airborne endotoxin (summer > winter).. endotoxin| house dust| humidity| indoor air pollution| seasonal variability| temperature|respiratory-infections| limulus assay| exposure| asthma| children| symptoms| dampness| severity| health| worker.	NOV-2000	endotoxin| house dust| humidity| indoor air pollution| seasonal variability| temperature|respiratory-infections| limulus assay| exposure| asthma| children| symptoms| dampness| severity| health| worker	Park, JH; Spiegelman, DL; Burge, HA; Gold, DR; Chew, GL; Milton, DK	Longitudinal study of dust and airborne endotoxin in the home		ENVIRONMENTAL HEALTH PERSPECTIVES	endotoxin; house dust; humidity; indoor air pollution; seasonal variability; temperature	RESPIRATORY-INFECTIONS; LIMULUS ASSAY; EXPOSURE; ASTHMA; CHILDREN; SYMPTOMS; DAMPNESS; SEVERITY; HEALTH; WORKER	To characterize the seasonal variability of endotoxin levels, we measured endotoxin in dust from the bed, bedroom floor, and kitchen floor in 20 homes, and in air from the bedroom in 15 of the homes. All homes were located in the greater Boston, Massachusetts, area and were sampled each month from April 1995 to June 1996. Outdoor air was collected at two locations. We found greater within-home than between-home variance for bedroom floor, kitchen floor, and airborne endotoxin. However, the reverse was true for bed dust endotoxin. Thus, studies using single measurements of dust endotoxin are most likely to reliably distinguish between homes if bed dust is sampled. Dust endotoxin levels were not significantly associated with airborne endotoxin. Airborne endotoxin was significantly (p = 0.04) and positively associated with absolute humidity in a mixed-effect model adjusting for a random home effect and fixed effect of sampling month and home characteristics. This finding implies that indoor humidity may be an important factor controlling endotoxin exposure. We found a significant (p < 0.05) seasonal effect in kitchen door dust (spring > fall) and bedroom airborne endotoxin (spring > winter), but not in the other indoor samples. We found significant seasonal pattern in outdoor airborne endotoxin (summer > winter).	32	111	2000	6	10.1289/ehp.001081023	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
"Internet-based home asthma telemonitoring - Can patients handle the technology?. Study objectice: To evaluate the validity of spirometry self-testing during home telemonitoring and to assess the acceptance of an Internet-based home asthma telemonitoring system by asthma patients. Design: We studied an Internet-based telemonitoring system that collected spirometry. data and symptom reports from asthma patients' homes for review by physicians in the medical center's clinical information system. After a 40-min training session, patients completed an electronic diary and performed spirometry testing twice daily on their own from their homes for 3 weeks. A medical professional visited each patient by the end of the third neck of monitoring, 10 to 40 min after the patient had performed self-testing, and asked the patient to perform the spirometry test again under his supervision, We evaluated the validity of self-testing and surveyed the patients attitude toward the technology using a standardized questionnaire, Setting: Telemonitoring was conducted in patients' homes in a low-income inner city area, Patients: Thirty-one consecutive asthma patients without regard to computer experience. Measurement and results: Thirty-one asthma patients completed 3 weeks of monitoring, A paired t test showed no difference between unsupervised and supervised home spirometry self-testing, The variability of FVC (4.1%), FEV(1), (3.7%), peak expiratory flow (7.9%), and other spirometric indexes in our study was similar to the within-subject variability reported by other researchers. Despite the fact that the majority of the patients (71%) had no computer experience, they indicated that the self-testing was ""not complicated at all"" or only ""slightly complicated."" The majority of patients (87.1%) were strongly interested in using home asthma telemonitoring in the future. Conclusions: Spirometry self-testing by asthma patients during telemonitoring is valid and comparable to those tests collected under the supervision of a trained medical professional, Internet-based home asthma telemonitoring can be successfully implemented in a group of patients with no computer background.. asthma| peak expiratory flow| self-management| spirometry| telemonitoring|expiratory flow-volume| quality-control| alpha(1)-antitrypsin deficiency| pulmonary-function| cystic-fibrosis| spirometry| variability| obstruction| children."	JAN-2000	asthma| peak expiratory flow| self-management| spirometry| telemonitoring|expiratory flow-volume| quality-control| alpha(1)-antitrypsin deficiency| pulmonary-function| cystic-fibrosis| spirometry| variability| obstruction| children	Finkelstein, J; Cabrera, MR; Hripcsak, G	Internet-based home asthma telemonitoring - Can patients handle the technology?		CHEST	asthma; peak expiratory flow; self-management; spirometry; telemonitoring	EXPIRATORY FLOW-VOLUME; QUALITY-CONTROL; ALPHA(1)-ANTITRYPSIN DEFICIENCY; PULMONARY-FUNCTION; CYSTIC-FIBROSIS; SPIROMETRY; VARIABILITY; OBSTRUCTION; CHILDREN	"Study objectice: To evaluate the validity of spirometry self-testing during home telemonitoring and to assess the acceptance of an Internet-based home asthma telemonitoring system by asthma patients. Design: We studied an Internet-based telemonitoring system that collected spirometry. data and symptom reports from asthma patients' homes for review by physicians in the medical center's clinical information system. After a 40-min training session, patients completed an electronic diary and performed spirometry testing twice daily on their own from their homes for 3 weeks. A medical professional visited each patient by the end of the third neck of monitoring, 10 to 40 min after the patient had performed self-testing, and asked the patient to perform the spirometry test again under his supervision, We evaluated the validity of self-testing and surveyed the patients attitude toward the technology using a standardized questionnaire, Setting: Telemonitoring was conducted in patients' homes in a low-income inner city area, Patients: Thirty-one consecutive asthma patients without regard to computer experience. Measurement and results: Thirty-one asthma patients completed 3 weeks of monitoring, A paired t test showed no difference between unsupervised and supervised home spirometry self-testing, The variability of FVC (4.1%), FEV(1), (3.7%), peak expiratory flow (7.9%), and other spirometric indexes in our study was similar to the within-subject variability reported by other researchers. Despite the fact that the majority of the patients (71%) had no computer experience, they indicated that the self-testing was ""not complicated at all"" or only ""slightly complicated."" The majority of patients (87.1%) were strongly interested in using home asthma telemonitoring in the future. Conclusions: Spirometry self-testing by asthma patients during telemonitoring is valid and comparable to those tests collected under the supervision of a trained medical professional, Internet-based home asthma telemonitoring can be successfully implemented in a group of patients with no computer background."	33	111	2000	8	10.1378/chest.117.1.148	General & Internal Medicine; Respiratory System
Ambient air pollution impairs regulatory T-cell function in asthma. Background: Asthma is the most frequent chronic disease in children, and children are at high risk for adverse health consequences associated with ambient air pollution (AAP) exposure. Regulatory T (Treg) cells are suppressors of immune responses involved in asthma pathogenesis. Treg-cell impairment is associated with increased DNA methylation of Forkhead box transcription factor 3 (Foxp3), a key transcription factor in Treg-cell activity. Because AAP exposure can induce epigenetic changes, we hypothesized that Treg-cell function would be impaired by AAP, allowing amplification of an inflammatory response. Objectives: To assess whether exposure to AAP led to hypermethylation of the Foxp3 gene, causing impaired Treg-cell suppression and worsened asthma symptom scores. Methods: Children with and without asthma from Fresno, Calif (high pollution, Fresno Asthma Group [FA], n = 71, and Fresno Non Asthmatic Group, n = 30, respectively), and from Stanford, Calif (low pollution, Stanford Asthma Group, n = 40, and Stanford Non Asthmatic Group, n 5 40), were enrolled in a cross-sectional study. Peripheral blood Treg cells were used in functional and epigenetic studies. Asthma outcomes were assessed by Global Initiative in Asthma score. Results: Fresno Asthma Group Treg-cell suppression was impaired and FA Treg-cell chemotaxis were reduced compared with other groups (P <= .05). Treg-cell dysfunction was associated with more pronounced decreases in asthma Global Initiative in Asthma score in FA versus the Stanford Asthma Group. Foxp3 was decreased in FA compared with the Fresno Non Asthmatic Group (P <= .05). FA also contained significantly higher levels of methylation at the Foxp3 locus (P <= .05). Conclusion: Increased exposure to AAP is associated with hypermethylation of the Foxp3 locus, impairing Treg-cell function and increasing asthma morbidity. AAP could play a role in mediating epigenetic changes in Treg cells, which may worsen asthma by an immune mechanism. (J Allergy Clin Immunol 2010;126:845-52.). ambient air pollution| asthma| immune system| regulatory t cell| treg| epigenetics|diesel exhaust particles| dna methylation| in-vivo| cytokine production| foxp3 expression| allergic-asthma| lung-function| exposure| challenge| children.	OCT-2010	ambient air pollution| asthma| immune system| regulatory t cell| treg| epigenetics|diesel exhaust particles| dna methylation| in-vivo| cytokine production| foxp3 expression| allergic-asthma| lung-function| exposure| challenge| children	Nadeau, K; McDonald-Hyman, C; Noth, EM; Pratt, B; Hammond, SK; Balmes, J; Tager, I	Ambient air pollution impairs regulatory T-cell function in asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Ambient air pollution; asthma; immune system; regulatory T cell; Treg; epigenetics	DIESEL EXHAUST PARTICLES; DNA METHYLATION; IN-VIVO; CYTOKINE PRODUCTION; FOXP3 EXPRESSION; ALLERGIC-ASTHMA; LUNG-FUNCTION; EXPOSURE; CHALLENGE; CHILDREN	Background: Asthma is the most frequent chronic disease in children, and children are at high risk for adverse health consequences associated with ambient air pollution (AAP) exposure. Regulatory T (Treg) cells are suppressors of immune responses involved in asthma pathogenesis. Treg-cell impairment is associated with increased DNA methylation of Forkhead box transcription factor 3 (Foxp3), a key transcription factor in Treg-cell activity. Because AAP exposure can induce epigenetic changes, we hypothesized that Treg-cell function would be impaired by AAP, allowing amplification of an inflammatory response. Objectives: To assess whether exposure to AAP led to hypermethylation of the Foxp3 gene, causing impaired Treg-cell suppression and worsened asthma symptom scores. Methods: Children with and without asthma from Fresno, Calif (high pollution, Fresno Asthma Group [FA], n = 71, and Fresno Non Asthmatic Group, n = 30, respectively), and from Stanford, Calif (low pollution, Stanford Asthma Group, n = 40, and Stanford Non Asthmatic Group, n 5 40), were enrolled in a cross-sectional study. Peripheral blood Treg cells were used in functional and epigenetic studies. Asthma outcomes were assessed by Global Initiative in Asthma score. Results: Fresno Asthma Group Treg-cell suppression was impaired and FA Treg-cell chemotaxis were reduced compared with other groups (P <= .05). Treg-cell dysfunction was associated with more pronounced decreases in asthma Global Initiative in Asthma score in FA versus the Stanford Asthma Group. Foxp3 was decreased in FA compared with the Fresno Non Asthmatic Group (P <= .05). FA also contained significantly higher levels of methylation at the Foxp3 locus (P <= .05). Conclusion: Increased exposure to AAP is associated with hypermethylation of the Foxp3 locus, impairing Treg-cell function and increasing asthma morbidity. AAP could play a role in mediating epigenetic changes in Treg cells, which may worsen asthma by an immune mechanism. (J Allergy Clin Immunol 2010;126:845-52.)	43	110	2010	18	10.1016/j.jaci.2010.08.008	Allergy; Immunology
The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA(2);LEN meta-analysis. Recent meta-analyses documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) and asthma (AA). Although SLIT appeared globally effective, the sub-analyses for single allergens provided uncertain results. This study is aimed to investigate the efficacy of SLIT with house dust mite (HDM) extracts in AR and AA through an updated reassessment of randomized controlled trials. Electronic databases were searched up to March 31, 2008, for randomized DBPC trials, assessing the efficacy of SLIT in AR and AA due to HDM sensitization. Outcomes were symptom scores and rescue medications use. For AR, eight studies fulfilled the selection criteria. A significant reduction in symptoms of AR (SMD -0.95; CI 95%-1.77 to -0.14 P = 0.02) was found in 194 patients (adults and children) receiving SLIT compared to 188 receiving placebo. For AA, with nine studies, similar results were found for symptoms (SMD -0.95; CI 95%-1.74 to -0.15 P = 0.02) in 243 patients (adults and children) receiving SLIT compared to 209 receiving placebo. A reduction in rescue medication use was found for AR (SMD -1.88; CI 95%-3.65 to -0.12 P = 0.04) in 89 patients, and AA (SMD -1.48; CI 95%-2.70 to -0.26 P = 0.02) in 202 patients. A relevant inter-study heterogeneity was detected. Promising evidence of efficacy for SLIT, using mite extract in allergic patients suffering from AR and AA, are herein shown. These findings suggest that more data are needed, derived from large-population-based high quality studies, and corroborated by objective outcomes, mainly for AA.. efficacy| house dust mites| meta-analysis| specific immunotherapy|randomized-clinical-trials| double-blind| pediatric-patients| rhinitis| asthma| children| collaboration| organization| reviews| quality.	NOV-2009	efficacy| house dust mites| meta-analysis| specific immunotherapy|randomized-clinical-trials| double-blind| pediatric-patients| rhinitis| asthma| children| collaboration| organization| reviews| quality	Compalati, E; Passalacqua, G; Bonini, M; Canonica, GW	The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA(2);LEN meta-analysis		ALLERGY	efficacy; house dust mites; meta-analysis; specific immunotherapy	RANDOMIZED-CLINICAL-TRIALS; DOUBLE-BLIND; PEDIATRIC-PATIENTS; RHINITIS; ASTHMA; CHILDREN; COLLABORATION; ORGANIZATION; REVIEWS; QUALITY	Recent meta-analyses documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic rhinitis (AR) and asthma (AA). Although SLIT appeared globally effective, the sub-analyses for single allergens provided uncertain results. This study is aimed to investigate the efficacy of SLIT with house dust mite (HDM) extracts in AR and AA through an updated reassessment of randomized controlled trials. Electronic databases were searched up to March 31, 2008, for randomized DBPC trials, assessing the efficacy of SLIT in AR and AA due to HDM sensitization. Outcomes were symptom scores and rescue medications use. For AR, eight studies fulfilled the selection criteria. A significant reduction in symptoms of AR (SMD -0.95; CI 95%-1.77 to -0.14 P = 0.02) was found in 194 patients (adults and children) receiving SLIT compared to 188 receiving placebo. For AA, with nine studies, similar results were found for symptoms (SMD -0.95; CI 95%-1.74 to -0.15 P = 0.02) in 243 patients (adults and children) receiving SLIT compared to 209 receiving placebo. A reduction in rescue medication use was found for AR (SMD -1.88; CI 95%-3.65 to -0.12 P = 0.04) in 89 patients, and AA (SMD -1.48; CI 95%-2.70 to -0.26 P = 0.02) in 202 patients. A relevant inter-study heterogeneity was detected. Promising evidence of efficacy for SLIT, using mite extract in allergic patients suffering from AR and AA, are herein shown. These findings suggest that more data are needed, derived from large-population-based high quality studies, and corroborated by objective outcomes, mainly for AA.	33	110	2009	10	10.1111/j.1398-9995.2009.02129.x	Allergy; Immunology
The role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: A systematic review and meta-analysis. BACKGROUND: Phthalates from polyvinyl chloride (PVC) plastics may have adverse effects on airways and immunologic systems, but the evidence has not been reviewed systematically. OBJECTIVE: We reviewed the evidence for the role of exposure to phthalates from PVC products in the development of asthma and allergies. Methods: We conducted a Medline database search (1950 through May 2007) for relevant studies on the respiratory and allergic effects of exposure to phthalates from PVC products. RESULTS: We based this review on 27 human and 14 laboratory toxicology studies. Two mouse inhalation experiments indicated that mono-2-ethylhexyl phthalate (MEHP) has the ability to modulate the immune response to exposure to a coallergen. The data suggested a no observed effect level of 30 mu g MEHp/m(3), calculated to be below the estimated level of human exposure in common environments. Case reports and series (n = 9) identified and verified cases of asthma that were very likely caused by fumes emitted from PVC film. Epidemiologic studies in adults (n = 10), mostly small studies in occupational settings, showed associations between heated PVC fumes and asthma and respiratory symptoms; studies in children (n = 5) showed an association between PVC surface materials in the home and the risk of asthma [fixed-effects model: summary odds ratio (OR), 1.55; 95% confidence interval (CI), 1.18-2-05; four studies] and allergies (OR, 1.32; 95% CI, 1.09-1.60; three studies). CONCLUSIONS: High levels of phthalates from PVC products can modulate the murine immune response to a coallergen. Heated PVC fumes possibly contribute to development of asthma in adults. Epidemiologic studies in children show associations between indicators of phthalate exposure in the home and risk of asthma and allergies. The lack of objective exposure information limits the epidemiologic data.. allergy| asthma| phthalates| polyvinyl chloride|meat-wrappers asthma| subcutaneous injection model| interior surface materials| balb/c mice| di-(2-ethylhexyl) phthalate| mono-2-ethylhexyl phthalate| occupational asthma| pulmonary-function| respiratory-tract| young-children.	JUL-2008	allergy| asthma| phthalates| polyvinyl chloride|meat-wrappers asthma| subcutaneous injection model| interior surface materials| balb/c mice| di-(2-ethylhexyl) phthalate| mono-2-ethylhexyl phthalate| occupational asthma| pulmonary-function| respiratory-tract| young-children	Jaakkola, JJK; Knight, TL	The role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: A systematic review and meta-analysis		ENVIRONMENTAL HEALTH PERSPECTIVES	allergy; asthma; phthalates; polyvinyl chloride	MEAT-WRAPPERS ASTHMA; SUBCUTANEOUS INJECTION MODEL; INTERIOR SURFACE MATERIALS; BALB/C MICE; DI-(2-ETHYLHEXYL) PHTHALATE; MONO-2-ETHYLHEXYL PHTHALATE; OCCUPATIONAL ASTHMA; PULMONARY-FUNCTION; RESPIRATORY-TRACT; YOUNG-CHILDREN	BACKGROUND: Phthalates from polyvinyl chloride (PVC) plastics may have adverse effects on airways and immunologic systems, but the evidence has not been reviewed systematically. OBJECTIVE: We reviewed the evidence for the role of exposure to phthalates from PVC products in the development of asthma and allergies. Methods: We conducted a Medline database search (1950 through May 2007) for relevant studies on the respiratory and allergic effects of exposure to phthalates from PVC products. RESULTS: We based this review on 27 human and 14 laboratory toxicology studies. Two mouse inhalation experiments indicated that mono-2-ethylhexyl phthalate (MEHP) has the ability to modulate the immune response to exposure to a coallergen. The data suggested a no observed effect level of 30 mu g MEHp/m(3), calculated to be below the estimated level of human exposure in common environments. Case reports and series (n = 9) identified and verified cases of asthma that were very likely caused by fumes emitted from PVC film. Epidemiologic studies in adults (n = 10), mostly small studies in occupational settings, showed associations between heated PVC fumes and asthma and respiratory symptoms; studies in children (n = 5) showed an association between PVC surface materials in the home and the risk of asthma [fixed-effects model: summary odds ratio (OR), 1.55; 95% confidence interval (CI), 1.18-2-05; four studies] and allergies (OR, 1.32; 95% CI, 1.09-1.60; three studies). CONCLUSIONS: High levels of phthalates from PVC products can modulate the murine immune response to a coallergen. Heated PVC fumes possibly contribute to development of asthma in adults. Epidemiologic studies in children show associations between indicators of phthalate exposure in the home and risk of asthma and allergies. The lack of objective exposure information limits the epidemiologic data.	58	110	2008	9	10.1289/ehp.10846	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Physiology of airway mucus secretion and pathophysiology of hypersecretion. Mucus secretion is the first-line defense against the barrage of irritants that inhalation of approximately 500 L of air an hour brings into the lungs. The inhaled soot, dust, microbes, and gases can all damage the airway epithelium. Consequently, mucus secretion is extremely rapid, occurring in tens of milliseconds. In addition, mucus is held in cytoplasmic granules in a highly condensed state in which high concentrations of Ca2+ nullify the repulsive forces of the highly polyanionic mucin molecules. Upon initiation of secretion and dilution of the Ca2+, the repulsion forces of the mucin molecules cause many-hundred-fold swelling of the secreted mucus, to cover and protect the epithelium. Secretion is a highly regulated process, with coordination by several molecules, including soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) proteins, myristoylated alanine-rich C kinase substrate (MARCKS), and Munc proteins, to dock the mucin granules to the secretory cell membrane prior to exocytosis. Because mucus secretion appears to be such a fundamental airway homeostatic process, virtually all regulatory and inflammatory mediators and interventions that have been investigated increase secretion acutely. When given longer-term, many of these same mediators also increase mucin gene expression and mucin synthesis, and induce goblet cell hyperplasia. These responses induce (in contrast to the protective effects of acute secretion) long-term, chronic hypersecretion of airway mucus, which contributes to respiratory disease. In this case the homeostatic, protective function of airway mucus secretion is lost, and, instead, mucus hypersecretion contributes to pathophysiology of a number of severe respiratory conditions, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.. mucin| mucus| asthma| chronic obstructive pulmonary disease| cystic fibrosis|goblet cell hyperplasia| obstructive pulmonary-disease| human mucin genes| respiratory-tract| mucociliary clearance| cystic-fibrosis| peripheral airways| surface epithelium| chronic-bronchitis| status-asthmaticus.	SEP-2007	mucin| mucus| asthma| chronic obstructive pulmonary disease| cystic fibrosis|goblet cell hyperplasia| obstructive pulmonary-disease| human mucin genes| respiratory-tract| mucociliary clearance| cystic-fibrosis| peripheral airways| surface epithelium| chronic-bronchitis| status-asthmaticus	Rogers, DF	Physiology of airway mucus secretion and pathophysiology of hypersecretion		RESPIRATORY CARE	mucin; mucus; asthma; chronic obstructive pulmonary disease; cystic fibrosis	GOBLET CELL HYPERPLASIA; OBSTRUCTIVE PULMONARY-DISEASE; HUMAN MUCIN GENES; RESPIRATORY-TRACT; MUCOCILIARY CLEARANCE; CYSTIC-FIBROSIS; PERIPHERAL AIRWAYS; SURFACE EPITHELIUM; CHRONIC-BRONCHITIS; STATUS-ASTHMATICUS	Mucus secretion is the first-line defense against the barrage of irritants that inhalation of approximately 500 L of air an hour brings into the lungs. The inhaled soot, dust, microbes, and gases can all damage the airway epithelium. Consequently, mucus secretion is extremely rapid, occurring in tens of milliseconds. In addition, mucus is held in cytoplasmic granules in a highly condensed state in which high concentrations of Ca2+ nullify the repulsive forces of the highly polyanionic mucin molecules. Upon initiation of secretion and dilution of the Ca2+, the repulsion forces of the mucin molecules cause many-hundred-fold swelling of the secreted mucus, to cover and protect the epithelium. Secretion is a highly regulated process, with coordination by several molecules, including soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) proteins, myristoylated alanine-rich C kinase substrate (MARCKS), and Munc proteins, to dock the mucin granules to the secretory cell membrane prior to exocytosis. Because mucus secretion appears to be such a fundamental airway homeostatic process, virtually all regulatory and inflammatory mediators and interventions that have been investigated increase secretion acutely. When given longer-term, many of these same mediators also increase mucin gene expression and mucin synthesis, and induce goblet cell hyperplasia. These responses induce (in contrast to the protective effects of acute secretion) long-term, chronic hypersecretion of airway mucus, which contributes to respiratory disease. In this case the homeostatic, protective function of airway mucus secretion is lost, and, instead, mucus hypersecretion contributes to pathophysiology of a number of severe respiratory conditions, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.	83	110	2007	16		General & Internal Medicine; Respiratory System
Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Background & Aims: Eosinophilic esophagitis (EE) is frequently associated with atopic disease, including dermatitis and asthma. Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE. Methods: Wild-type and genetically engineered mice were subjected to epicutaneous antigen sensitization and the development of experimental EE, and immune responses were examined. Results: We show that exposure to antigen via the epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by a single airway antigen challenge. The development of experimental EE is associated with significant skin eosinophilia, accelerated bone marrow eosinophilopoiesis, blood eosinophilia, and large increases in serum antigen-specific immunoglobulin G1/immunoglobulin E using ovalbumin or Aspergillus fumigatus as the epicutaneous antigen. Mechanistic analysis with gene-targeted mice showed that interleukin-5 was required for esophageal eosinophilia and that interleukin-4, interleukin-13, and STAT6 contributed to a lesser extent. Conclusions: These findings provide the first evidence that epicutaneous exposure to allergens potently primes for EE via a Th2-dependent mechanism.. stat6-deficient mice| atopic-dermatitis| airway hyperresponsiveness| gastrointestinal disorders| allergic dermatitis| murine model| t-cells| asthma| children| il-5.	SEP-2005	stat6-deficient mice| atopic-dermatitis| airway hyperresponsiveness| gastrointestinal disorders| allergic dermatitis| murine model| t-cells| asthma| children| il-5	Akei, HS; Mishra, A; Blanchard, C; Rothenberg, ME	Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice		GASTROENTEROLOGY		STAT6-DEFICIENT MICE; ATOPIC-DERMATITIS; AIRWAY HYPERRESPONSIVENESS; GASTROINTESTINAL DISORDERS; ALLERGIC DERMATITIS; MURINE MODEL; T-CELLS; ASTHMA; CHILDREN; IL-5	Background & Aims: Eosinophilic esophagitis (EE) is frequently associated with atopic disease, including dermatitis and asthma. Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE. Methods: Wild-type and genetically engineered mice were subjected to epicutaneous antigen sensitization and the development of experimental EE, and immune responses were examined. Results: We show that exposure to antigen via the epicutaneous route primes for marked eosinophilic inflammation in the esophagus triggered by a single airway antigen challenge. The development of experimental EE is associated with significant skin eosinophilia, accelerated bone marrow eosinophilopoiesis, blood eosinophilia, and large increases in serum antigen-specific immunoglobulin G1/immunoglobulin E using ovalbumin or Aspergillus fumigatus as the epicutaneous antigen. Mechanistic analysis with gene-targeted mice showed that interleukin-5 was required for esophageal eosinophilia and that interleukin-4, interleukin-13, and STAT6 contributed to a lesser extent. Conclusions: These findings provide the first evidence that epicutaneous exposure to allergens potently primes for EE via a Th2-dependent mechanism.	55	110	2005	10	10.1053/j.gastro.2005.06.027	Gastroenterology & Hepatology
Home dampness and molds, parental atopy, and asthma in childhood: A six-year population-based cohort study. Previous studies of how parental atopy and exposure to dampness and molds contribute to the risk of asthma have been mainly cross-sectional or prevalent case-control studies, where selection and information bias and temporality constitute problems. We assessed longitudinally the independent and joint effects of parental atopy and exposure to molds in dwellings on the development of asthma in childhood. We conducted a population-based, 6-year prospective cohort study of 1,984 children 1-7 years of age at the baseline in 1991 (follow-up rate, 77%). The study population included 1,916 children without asthma at baseline and complete outcome information. The data collection included a baseline and follow-up survey. The outcome of interest was development of asthma during the study period. The studied determinants were parental allergic diseases and four indicators of exposure at baseline: histories of water damage, presence of moisture and visible molds, and perceived mold odor in the home. A total of 138 (7.2%) children developed asthma during the study period, resulting in an incidence rate of 125 cases per 10,000 person-years [95% confidence interval (CI), 104-146]. In Poisson regression adjusting for confounding, parental atopy [adjusted incidence rate ratio (IRR) 1.52; 95% Cl, 1.08-2.13] and the presence of mold odor in the home reported at baseline (adjusted IRR 2.44; 95% Cl, 1.07-5.60) were independent determinants of asthma incidence, but no apparent interaction was observed. The results of this cohort study with assessment of exposure before the onset of asthma strengthen the evidence on the independent effects of parental atopy and exposure to molds on the development of asthma.. asthma| damp housing| effect modification| interaction| molds|environmental-factors| respiratory symptoms| children| health| inflammation| signs.	MAR-2005	asthma| damp housing| effect modification| interaction| molds|environmental-factors| respiratory symptoms| children| health| inflammation| signs	Jaakkola, JJK; Hwang, BF; Jaakkola, N	Home dampness and molds, parental atopy, and asthma in childhood: A six-year population-based cohort study		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; damp housing; effect modification; interaction; molds	ENVIRONMENTAL-FACTORS; RESPIRATORY SYMPTOMS; CHILDREN; HEALTH; INFLAMMATION; SIGNS	Previous studies of how parental atopy and exposure to dampness and molds contribute to the risk of asthma have been mainly cross-sectional or prevalent case-control studies, where selection and information bias and temporality constitute problems. We assessed longitudinally the independent and joint effects of parental atopy and exposure to molds in dwellings on the development of asthma in childhood. We conducted a population-based, 6-year prospective cohort study of 1,984 children 1-7 years of age at the baseline in 1991 (follow-up rate, 77%). The study population included 1,916 children without asthma at baseline and complete outcome information. The data collection included a baseline and follow-up survey. The outcome of interest was development of asthma during the study period. The studied determinants were parental allergic diseases and four indicators of exposure at baseline: histories of water damage, presence of moisture and visible molds, and perceived mold odor in the home. A total of 138 (7.2%) children developed asthma during the study period, resulting in an incidence rate of 125 cases per 10,000 person-years [95% confidence interval (CI), 104-146]. In Poisson regression adjusting for confounding, parental atopy [adjusted incidence rate ratio (IRR) 1.52; 95% Cl, 1.08-2.13] and the presence of mold odor in the home reported at baseline (adjusted IRR 2.44; 95% Cl, 1.07-5.60) were independent determinants of asthma incidence, but no apparent interaction was observed. The results of this cohort study with assessment of exposure before the onset of asthma strengthen the evidence on the independent effects of parental atopy and exposure to molds on the development of asthma.	21	110	2005	5	10.1289/ehp.7242	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Asthma and depressive and anxiety disorders among young persons in the community. Background. The objectives of the study were to examine linkages between asthma and depressive and anxiety disorders in a birth cohort of over 1000 young persons studied to the age of 21 years. Specifically, the study aimed to ascertain the extent to which associations between asthma and depressive and anxiety disorders could be explained by non-observed fixed confounding factors. Method. Asthma and depressive and anxiety disorders were measured prospectively over the course of a 21-year longitudinal study. Fixed effects logistic regression models were used to determine the relationship between asthma and depressive and anxiety disorders, adjusting for potentially confounding factors. Results. Asthma in adolescence and young adulthood was associated with increased likelihood of major depression (OR 1(.)7, 95 % CI 1(.)3-2(.)3), panic attacks (OR 1(.)9, 95 % CI 1(.)3-2(.)8), and any anxiety disorder (OR 1(.)6, 95% CI 1(.)2-2(.)2). Associations between asthma and depressive and anxiety disorders were adjusted for confounding factors using a fixed effects regression model which showed that, after control for fixed confounding factors, asthma was no longer significantly related to major depression (OR 1(.)1), panic attacks (OR 1(.)1),or any anxiety disorder (OR 1(.)2). Additional post hoe analyses suggested that exposure to childhood adversity or unexamined familial factors may account for some of the co-morbidity of asthma and depressive and anxiety disorders. Conclusions. These results confirm and extend previous findings by documenting elevated rates of depressive and anxiety disorders among young adults with asthma, compared with their counterparts without asthma, in the community. The weight of the evidence from this study suggests that associations between asthma and depressive and anxiety symptoms may reflect effects of common factors associated with both asthma and depressive and anxiety disorders, rather than a direct causal link. Future research is needed to identify the specific factors underlying these associations.. posttraumatic-stress-disorder| psychiatric-disorders| functional status| panic disorder| children| prevalence| childhood| morbidity| outcomes| outpatients.	NOV-2004	posttraumatic-stress-disorder| psychiatric-disorders| functional status| panic disorder| children| prevalence| childhood| morbidity| outcomes| outpatients	Goodwin, RD; Fergusson, DM; Horwood, LJ	Asthma and depressive and anxiety disorders among young persons in the community		PSYCHOLOGICAL MEDICINE		POSTTRAUMATIC-STRESS-DISORDER; PSYCHIATRIC-DISORDERS; FUNCTIONAL STATUS; PANIC DISORDER; CHILDREN; PREVALENCE; CHILDHOOD; MORBIDITY; OUTCOMES; OUTPATIENTS	Background. The objectives of the study were to examine linkages between asthma and depressive and anxiety disorders in a birth cohort of over 1000 young persons studied to the age of 21 years. Specifically, the study aimed to ascertain the extent to which associations between asthma and depressive and anxiety disorders could be explained by non-observed fixed confounding factors. Method. Asthma and depressive and anxiety disorders were measured prospectively over the course of a 21-year longitudinal study. Fixed effects logistic regression models were used to determine the relationship between asthma and depressive and anxiety disorders, adjusting for potentially confounding factors. Results. Asthma in adolescence and young adulthood was associated with increased likelihood of major depression (OR 1(.)7, 95 % CI 1(.)3-2(.)3), panic attacks (OR 1(.)9, 95 % CI 1(.)3-2(.)8), and any anxiety disorder (OR 1(.)6, 95% CI 1(.)2-2(.)2). Associations between asthma and depressive and anxiety disorders were adjusted for confounding factors using a fixed effects regression model which showed that, after control for fixed confounding factors, asthma was no longer significantly related to major depression (OR 1(.)1), panic attacks (OR 1(.)1),or any anxiety disorder (OR 1(.)2). Additional post hoe analyses suggested that exposure to childhood adversity or unexamined familial factors may account for some of the co-morbidity of asthma and depressive and anxiety disorders. Conclusions. These results confirm and extend previous findings by documenting elevated rates of depressive and anxiety disorders among young adults with asthma, compared with their counterparts without asthma, in the community. The weight of the evidence from this study suggests that associations between asthma and depressive and anxiety symptoms may reflect effects of common factors associated with both asthma and depressive and anxiety disorders, rather than a direct causal link. Future research is needed to identify the specific factors underlying these associations.	37	110	2004	10	10.1017/S0033291704002739	Psychology; Psychiatry
Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real-life: clinical efficacy and more. Background: Some aspects of sublingual immunotherapy (SLIT) still need to be addressed: magnitude of the clinical efficacy, effect on the bronchial hyperreactivity adherence to treatment, preventive effect. We attempted to clarify these points in a randomized open, controlled, two parallel group study in a real-life setting. Methods: Five hundred and eleven patients with allergic rhinitis with or without intermittent asthma were randomized to drugs only or drugs + SLIT (rate 2 : 3) for 3 years. The clinical score (symptoms + drug intake) was measured each year during the allergen exposure. Pulmonary function test, methacholine challenge and skin tests were performed at the beginning and at the end of the study. Adherence to treatment was assessed by measuring the consumed extract. Results: Three hundred and nineteen patients received SLIT and 192 drugs only. Dropouts were 15% in the SLIT group and 12% in the controls. There was a significant improvement of clinical scores in the SLIT group: baseline 147 +/- 3.3, first year 72.9 +/- 1.3, second year 68.3 +/- 1.8, third year 54.7 +/- 2.8 (P < 0.0001 vs baseline). Control group: baseline 138 +/- 2.3, first year 124.1 +/- 3.7, second year 111 +/- 3.3, third year 121 +/- 3.8 (P = NS). Only four patients reported systemic itching. Adherence was >80% in 72% and >60% in 18% of patients. The number of patients with a positive MCh challenge decreased significantly after 3 years only in the SLIT group. New skin sensitizations appeared in 38% of the controls and in 5.9% of the SLIT patients (P = 0.01). Conclusion: Sublingual immunotherapy approximately halved the clinical scores and significantly reduced the bronchial hyperreactivity. Similarly to subcutaneous immunotherapy, SLIT displayed a preventive effect on the onset of new skin sensitizations. The adherence rate was quantitatively satisfactory.. adherence| bronchial hyperreactivity| preventive effect| respiratory allergy| sublingual immunotherapy|house-dust mite| controlled-trial| seasonal rhinoconjunctivitis| double-blind| asthma| children| sensitizations| standardization| responsiveness| prevention.	NOV-2004	adherence| bronchial hyperreactivity| preventive effect| respiratory allergy| sublingual immunotherapy|house-dust mite| controlled-trial| seasonal rhinoconjunctivitis| double-blind| asthma| children| sensitizations| standardization| responsiveness| prevention	Marogna, M; Spadolini, I; Massolo, A; Canonica, GW; Passalacqua, G	Randomized controlled open study of sublingual immunotherapy for respiratory allergy in real-life: clinical efficacy and more		ALLERGY	adherence; bronchial hyperreactivity; preventive effect; respiratory allergy; sublingual immunotherapy	HOUSE-DUST MITE; CONTROLLED-TRIAL; SEASONAL RHINOCONJUNCTIVITIS; DOUBLE-BLIND; ASTHMA; CHILDREN; SENSITIZATIONS; STANDARDIZATION; RESPONSIVENESS; PREVENTION	Background: Some aspects of sublingual immunotherapy (SLIT) still need to be addressed: magnitude of the clinical efficacy, effect on the bronchial hyperreactivity adherence to treatment, preventive effect. We attempted to clarify these points in a randomized open, controlled, two parallel group study in a real-life setting. Methods: Five hundred and eleven patients with allergic rhinitis with or without intermittent asthma were randomized to drugs only or drugs + SLIT (rate 2 : 3) for 3 years. The clinical score (symptoms + drug intake) was measured each year during the allergen exposure. Pulmonary function test, methacholine challenge and skin tests were performed at the beginning and at the end of the study. Adherence to treatment was assessed by measuring the consumed extract. Results: Three hundred and nineteen patients received SLIT and 192 drugs only. Dropouts were 15% in the SLIT group and 12% in the controls. There was a significant improvement of clinical scores in the SLIT group: baseline 147 +/- 3.3, first year 72.9 +/- 1.3, second year 68.3 +/- 1.8, third year 54.7 +/- 2.8 (P < 0.0001 vs baseline). Control group: baseline 138 +/- 2.3, first year 124.1 +/- 3.7, second year 111 +/- 3.3, third year 121 +/- 3.8 (P = NS). Only four patients reported systemic itching. Adherence was >80% in 72% and >60% in 18% of patients. The number of patients with a positive MCh challenge decreased significantly after 3 years only in the SLIT group. New skin sensitizations appeared in 38% of the controls and in 5.9% of the SLIT patients (P = 0.01). Conclusion: Sublingual immunotherapy approximately halved the clinical scores and significantly reduced the bronchial hyperreactivity. Similarly to subcutaneous immunotherapy, SLIT displayed a preventive effect on the onset of new skin sensitizations. The adherence rate was quantitatively satisfactory.	34	110	2004	6	10.1111/j.1398-9995.2004.00508.x	Allergy; Immunology
Matrix metalloproteinase-9 expression in asthma - Effect of asthma severity, allergen challenge, and inhaled corticosteroids. Background: Asthma is associated with remodeling of the extracellular matrix (ECM) and increased airway obstruction, and the mechanisms of this process are unknown. Matrix metalloproteinases (MMPs) are a group of enzymes capable of degrading the ECM. They are released along with their inhibitors, tissue inhibitor of MMP (TIMP). Study objectives: To determine whether severe, persistent asthma is associated with increased levels of MMP-9 in the airway compared with mild asthma, and to assess the effect of both allergen exposure and steroid treatment on MMP-9 and TIMP-1 levels. Design: Prospective analysis of levels and activity of MMP-9 and TIMP-1 in BAL fluid (BALF) and induced sputum obtained from asthmatics of differing disease severity. In patients with mild asthma, MMP-9 and TIMP-1 levels were studied in induced sputum following allergen challenge and in BALF after inhaled steroid therapy. Patients: Eighteen patients with mild asthma, 10 patients with severe asthma, and 10 nonsmoking, atopic subjects had their sputum studied. Fourteen of the patients with mild asthma underwent allergen challenge. BAL was collected from 16 patients with mild asthma before and after 4 weeks treatment with inhaled budesonide, 800 mug bid, or placebo. Results: Patients with severe asthma had increased levels and activity of sputum MMP-9 in their sputum compared with patients with mild asthma and normal subjects. Allergen challenge increased the MMP-9/TIMP-1 ratio and MMP-9 activity. Inhaled budesonide had no effect on MMP-9 or TIMP-1 in patients with mild asthma. Conclusions: MMP-9 may play a role in chronic airway inflammation and remodeling in asthma, as concentrations are increased in severe, persistent asthma and following allergen challenge. Inhaled steroids may not affect MMP-9 and TIMP in patients with mild asthma, and additional studies in patients with more severe asthma are needed.. allergen challenge| asthma| corticosteroid| matrix metalloproteinase| matrix metalloproteinase-9| tisstue inhibitors of matrix metalloproteinase|bronchoalveolar lavage fluid| matrix metalloproteinases| basement-membrane| tissue inhibitor| 92-kda gelatinase| iv collagenase| tnf-alpha| alveolar macrophages| airway inflammation| timp-1 production.	NOV-2002	allergen challenge| asthma| corticosteroid| matrix metalloproteinase| matrix metalloproteinase-9| tisstue inhibitors of matrix metalloproteinase|bronchoalveolar lavage fluid| matrix metalloproteinases| basement-membrane| tissue inhibitor| 92-kda gelatinase| iv collagenase| tnf-alpha| alveolar macrophages| airway inflammation| timp-1 production	Mattos, W; Lim, S; Russell, R; Jatakanon, A; Chung, F; Barnes, PJ	Matrix metalloproteinase-9 expression in asthma - Effect of asthma severity, allergen challenge, and inhaled corticosteroids		CHEST	allergen challenge; asthma; corticosteroid; matrix metalloproteinase; matrix metalloproteinase-9; tisstue inhibitors of matrix metalloproteinase	BRONCHOALVEOLAR LAVAGE FLUID; MATRIX METALLOPROTEINASES; BASEMENT-MEMBRANE; TISSUE INHIBITOR; 92-KDA GELATINASE; IV COLLAGENASE; TNF-ALPHA; ALVEOLAR MACROPHAGES; AIRWAY INFLAMMATION; TIMP-1 PRODUCTION	Background: Asthma is associated with remodeling of the extracellular matrix (ECM) and increased airway obstruction, and the mechanisms of this process are unknown. Matrix metalloproteinases (MMPs) are a group of enzymes capable of degrading the ECM. They are released along with their inhibitors, tissue inhibitor of MMP (TIMP). Study objectives: To determine whether severe, persistent asthma is associated with increased levels of MMP-9 in the airway compared with mild asthma, and to assess the effect of both allergen exposure and steroid treatment on MMP-9 and TIMP-1 levels. Design: Prospective analysis of levels and activity of MMP-9 and TIMP-1 in BAL fluid (BALF) and induced sputum obtained from asthmatics of differing disease severity. In patients with mild asthma, MMP-9 and TIMP-1 levels were studied in induced sputum following allergen challenge and in BALF after inhaled steroid therapy. Patients: Eighteen patients with mild asthma, 10 patients with severe asthma, and 10 nonsmoking, atopic subjects had their sputum studied. Fourteen of the patients with mild asthma underwent allergen challenge. BAL was collected from 16 patients with mild asthma before and after 4 weeks treatment with inhaled budesonide, 800 mug bid, or placebo. Results: Patients with severe asthma had increased levels and activity of sputum MMP-9 in their sputum compared with patients with mild asthma and normal subjects. Allergen challenge increased the MMP-9/TIMP-1 ratio and MMP-9 activity. Inhaled budesonide had no effect on MMP-9 or TIMP-1 in patients with mild asthma. Conclusions: MMP-9 may play a role in chronic airway inflammation and remodeling in asthma, as concentrations are increased in severe, persistent asthma and following allergen challenge. Inhaled steroids may not affect MMP-9 and TIMP in patients with mild asthma, and additional studies in patients with more severe asthma are needed.	38	110	2002	10	10.1378/chest.122.5.1543	General & Internal Medicine; Respiratory System
The influence of ambient coarse particulate matter on asthma hospitalization in children: Case-crossover and time-series analyses. In this study, we used both case-crossover and time-series analyses to assess the associations between size-fractionated particulate matter and asthma hospitalization among children 6-12 years old living in Toronto between 1981 and 1993. Specifically, we used exposures averaged over periods varying from 1 to 7 days to assess the effects of particulate matter on asthma hospitalization. We calculated estimates of the relative risk of asthma hospitalization adjusted for daily weather conditions (maximum and minimum temperatures, and average relative humidity) for an incremental exposure corresponding to the interquartile range in particulate matter. Both bidirectional case-crossover and time-series analyses revealed that coarse particulate matter (PM10-2.5) averaged over 5-6 days was significantly associated with asthma hospitalization in both males and females. The magnitude of this effect appeared to increase with increasing number of days of exposure averaging for most models, with the relative risk estimates stabilizing at about 6 days. Using a bidirectional case-crossover analysis, the estimated relative risks were 1.14 [95% confidence interval (CI), 1.02, 1.28] for males and 1.18 (95% CI, 1.02, 1.36) for females, for an increment of 8.4 mug/m(3) in 6-day averages of PM10-2.5. The corresponding relative risk estimates were 1.10 and 1.18, respectively, when we used time-series analysis. The effect Of PM10-2.5 remained positive after adjustment for the effects of the gaseous pollutants carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O-3). We did not find significant effects of fine particulate matter (PM2.5) or of thoracic particulate matter (PM10) on asthma hospitalizations using either of these two analytic approaches. For the most part, relative risk estimates from the unidirectional case-crossover analysis were more pronounced compared with both bidirectional case-crossover and time-series analyses.. asthma hospitalization| case-crossover analysis| coarse particulate matter| risk assessment| time-series analysis|carbon-monoxide levels| emergency room visits| air-pollution| daily mortality| fine particles| philadelphia| association| admissions| seattle| california.	JUN-2002	asthma hospitalization| case-crossover analysis| coarse particulate matter| risk assessment| time-series analysis|carbon-monoxide levels| emergency room visits| air-pollution| daily mortality| fine particles| philadelphia| association| admissions| seattle| california	Lin, M; Chen, Y; Burnett, RT; Villeneuve, PJ; Krewski, D	The influence of ambient coarse particulate matter on asthma hospitalization in children: Case-crossover and time-series analyses		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma hospitalization; case-crossover analysis; coarse particulate matter; risk assessment; time-series analysis	CARBON-MONOXIDE LEVELS; EMERGENCY ROOM VISITS; AIR-POLLUTION; DAILY MORTALITY; FINE PARTICLES; PHILADELPHIA; ASSOCIATION; ADMISSIONS; SEATTLE; CALIFORNIA	In this study, we used both case-crossover and time-series analyses to assess the associations between size-fractionated particulate matter and asthma hospitalization among children 6-12 years old living in Toronto between 1981 and 1993. Specifically, we used exposures averaged over periods varying from 1 to 7 days to assess the effects of particulate matter on asthma hospitalization. We calculated estimates of the relative risk of asthma hospitalization adjusted for daily weather conditions (maximum and minimum temperatures, and average relative humidity) for an incremental exposure corresponding to the interquartile range in particulate matter. Both bidirectional case-crossover and time-series analyses revealed that coarse particulate matter (PM10-2.5) averaged over 5-6 days was significantly associated with asthma hospitalization in both males and females. The magnitude of this effect appeared to increase with increasing number of days of exposure averaging for most models, with the relative risk estimates stabilizing at about 6 days. Using a bidirectional case-crossover analysis, the estimated relative risks were 1.14 [95% confidence interval (CI), 1.02, 1.28] for males and 1.18 (95% CI, 1.02, 1.36) for females, for an increment of 8.4 mug/m(3) in 6-day averages of PM10-2.5. The corresponding relative risk estimates were 1.10 and 1.18, respectively, when we used time-series analysis. The effect Of PM10-2.5 remained positive after adjustment for the effects of the gaseous pollutants carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O-3). We did not find significant effects of fine particulate matter (PM2.5) or of thoracic particulate matter (PM10) on asthma hospitalizations using either of these two analytic approaches. For the most part, relative risk estimates from the unidirectional case-crossover analysis were more pronounced compared with both bidirectional case-crossover and time-series analyses.	38	110	2002	7		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Expression and activity of pH-regulatory glutaminase in the human airway epithelium. Fluid condensed from the breath of patients with acute asthma is acidic. Several features of asthma pathophysiology can be initiated by exposure of the airway to acid. In renal tubular epithelium, glutaminase produces ammonia to buffer urinary acid excretion. We hypothesized that human airway epithelium could also express glutaminase. Here, we demonstrate that human airway epithelial cells in vitro have biochemical evidence for glutaminase activity and express mRNA for two glutaminase isoforms (KGA and GAC). Glutaminase activity increased in response to acidic stress (media PH 5.8) and was associated with both increased culture medium pH and improved cell survival. In contrast, activity was inhibited by interferon-gamma and tumor necrosis factor-a. Glutaminase protein was expressed in the human airway in vivo. Further, ammonia levels in the breath condensate of subjects with acute asthma were low (30 muM [range: 0-233], n = 18, age 23 +/- 2.5 yr) compared with control subjects (327 muM [14-1,220], n 24, age 24 +/- 2.4 yr, p < 0.001), and correlated with condensate pH (r = 0.58, p < 0.001). These data demonstrate that glutaminase is expressed and active in the human airway epithelium and may be relevant both to the regulation of airway pH and to the pathophysiology of acute asthmatic airway inflammation.. asthma| glutaminase| ammonia| lung| breath condensate|mycobacterium-tuberculosis| respiratory mucus| buffer capacity| surface liquid| tracheal| macrophages| ammonia| asthma| eosinophils| metabolism.	JAN 1-2002	asthma| glutaminase| ammonia| lung| breath condensate|mycobacterium-tuberculosis| respiratory mucus| buffer capacity| surface liquid| tracheal| macrophages| ammonia| asthma| eosinophils| metabolism	Hunt, JF; Erwin, E; Palmer, L; Vaughan, J; Malhotra, N; Platts-Mills, TAE; Gaston, B	Expression and activity of pH-regulatory glutaminase in the human airway epithelium		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; glutaminase; ammonia; lung; breath condensate	MYCOBACTERIUM-TUBERCULOSIS; RESPIRATORY MUCUS; BUFFER CAPACITY; SURFACE LIQUID; TRACHEAL; MACROPHAGES; AMMONIA; ASTHMA; EOSINOPHILS; METABOLISM	Fluid condensed from the breath of patients with acute asthma is acidic. Several features of asthma pathophysiology can be initiated by exposure of the airway to acid. In renal tubular epithelium, glutaminase produces ammonia to buffer urinary acid excretion. We hypothesized that human airway epithelium could also express glutaminase. Here, we demonstrate that human airway epithelial cells in vitro have biochemical evidence for glutaminase activity and express mRNA for two glutaminase isoforms (KGA and GAC). Glutaminase activity increased in response to acidic stress (media PH 5.8) and was associated with both increased culture medium pH and improved cell survival. In contrast, activity was inhibited by interferon-gamma and tumor necrosis factor-a. Glutaminase protein was expressed in the human airway in vivo. Further, ammonia levels in the breath condensate of subjects with acute asthma were low (30 muM [range: 0-233], n = 18, age 23 +/- 2.5 yr) compared with control subjects (327 muM [14-1,220], n 24, age 24 +/- 2.4 yr, p < 0.001), and correlated with condensate pH (r = 0.58, p < 0.001). These data demonstrate that glutaminase is expressed and active in the human airway epithelium and may be relevant both to the regulation of airway pH and to the pathophysiology of acute asthmatic airway inflammation.	45	110	2002	7		General & Internal Medicine; Respiratory System
Exercise-induced bronchospasm in the elite athlete. The term exercise-induced bronchospasm (EIB) describes the acute transient airway narrowing that occurs during and most often after exercise in 10 to 50% of elite athletes, depending upon the sport examined. Although multiple factors are unquestionably involved in the EIB response, airway drying caused by a high exercise-ventilation rate is primary in most cases. The severity of this reaction reflects the allergic predisposition of the athlete, the water content of the inspired air, the type and concentration of air pollutants inspired, and the intensity (or ventilation rate) of the exercise. The highest prevalence of EIB is seen in winter-sport populations, where athletes are chronically exposed to cold dry air and/or environmental pollutants found in indoor ice arenas. When airway surface liquid lost during the natural warming and humidification process of respiration is not replenished at a rate equal to the loss, the ensuing osmolarity change stimulates the release of inflammatory mediators and results in bronchospasm; this cascade of events is exacerbated by airway inflammation and airway remodelling. The acute EIB response is characterised by airway smooth muscle contraction, membrane swelling, and/or mucus plug formation. Evidence suggests that histamine, leukotrienes and prostanoids are likely mediators for this response. Although the presence of symptoms and a basic physical examination are marginally effective, objective measures of lung function should be used for accurate and reliable diagnosis of EIB. Diagnosis should include baseline spirometry, followed by an appropriate bronchial provocation test. To date, the best test to confirm EIB may simply be standard pulmonary function testing before and after high-intensity dry air exercise. A 10% post-challenge fall in forced expiratory volume in 1 second is used as diagnostic criteria. The goal of medical intervention is to limit EIB exacerbation and allow the athlete to train and compete symptom free. This is attempted through daily controller medications such as inhaled corticosteroids or by the prophylactic use of medications before exercise. In many cases, EIB is difficult to control. These and other data suggest that EIB in the elite athlete is in contrast with classic asthma.. cross-country skiers| ice skating rinks| hypertonic saline challenge| nitrogen-dioxide exposures| vocal cord dysfunction| induced asthma| induced bronchoconstriction| fluticasone propionate| receptor antagonist| water-loss.	2002	cross-country skiers| ice skating rinks| hypertonic saline challenge| nitrogen-dioxide exposures| vocal cord dysfunction| induced asthma| induced bronchoconstriction| fluticasone propionate| receptor antagonist| water-loss	Rundell, KW; Jenkinson, DM	Exercise-induced bronchospasm in the elite athlete		SPORTS MEDICINE		CROSS-COUNTRY SKIERS; ICE SKATING RINKS; HYPERTONIC SALINE CHALLENGE; NITROGEN-DIOXIDE EXPOSURES; VOCAL CORD DYSFUNCTION; INDUCED ASTHMA; INDUCED BRONCHOCONSTRICTION; FLUTICASONE PROPIONATE; RECEPTOR ANTAGONIST; WATER-LOSS	The term exercise-induced bronchospasm (EIB) describes the acute transient airway narrowing that occurs during and most often after exercise in 10 to 50% of elite athletes, depending upon the sport examined. Although multiple factors are unquestionably involved in the EIB response, airway drying caused by a high exercise-ventilation rate is primary in most cases. The severity of this reaction reflects the allergic predisposition of the athlete, the water content of the inspired air, the type and concentration of air pollutants inspired, and the intensity (or ventilation rate) of the exercise. The highest prevalence of EIB is seen in winter-sport populations, where athletes are chronically exposed to cold dry air and/or environmental pollutants found in indoor ice arenas. When airway surface liquid lost during the natural warming and humidification process of respiration is not replenished at a rate equal to the loss, the ensuing osmolarity change stimulates the release of inflammatory mediators and results in bronchospasm; this cascade of events is exacerbated by airway inflammation and airway remodelling. The acute EIB response is characterised by airway smooth muscle contraction, membrane swelling, and/or mucus plug formation. Evidence suggests that histamine, leukotrienes and prostanoids are likely mediators for this response. Although the presence of symptoms and a basic physical examination are marginally effective, objective measures of lung function should be used for accurate and reliable diagnosis of EIB. Diagnosis should include baseline spirometry, followed by an appropriate bronchial provocation test. To date, the best test to confirm EIB may simply be standard pulmonary function testing before and after high-intensity dry air exercise. A 10% post-challenge fall in forced expiratory volume in 1 second is used as diagnostic criteria. The goal of medical intervention is to limit EIB exacerbation and allow the athlete to train and compete symptom free. This is attempted through daily controller medications such as inhaled corticosteroids or by the prophylactic use of medications before exercise. In many cases, EIB is difficult to control. These and other data suggest that EIB in the elite athlete is in contrast with classic asthma.	140	110	2002	18	10.2165/00007256-200232090-00004	Sport Sciences
Effects of ambient air pollution on symptoms of asthma in Seattle-area children enrolled in the CAMP study. We observed a panel of 133 children (5-13 years of age) with asthma residing in the greater Seattle, Washington, area for an average of 58 days (range 28-112 days) during screening for enrollment in the Childhood Asthma Management Program (CAMP) study. Daily self-reports of asthma symp toms were obtained from study diaries and compared with ambient air pollution levels in marginal repeated measures logistic regression models. We defined days with asthma symptoms as any day a child reported at least one mild asthma episode. All analyses were controlled for subject-specific variables [age, race, sex, baseline height, and FEV1 PC20 concentration (methacholine provocative concentration required to produce a 20% decrease in forced expiratory volume in 1 sec)] and potential rime-dependent confounders (day of week, season, and temperature). Because of variable observation periods for participants, we estimated both between- and within-subject air pollutant effects. Our primary interest was in the within-subject effects: the effect of air pollutant excursions from typical levels in each child's observation period on the odds of asthma symptoms. In single-pollutant models, the population average estimates indicated a 30% [95% confidence interval (CI), 11-52%] increase for a 1-ppm increment in carbon monoxide lagged I day, an 18% (95% CI, 5-33%) increase for a 10-mug/m(3) increment in same-day particulate matter < 1.0 <mu>m (PM1.0), and an 11% (95% CI, 3-20%) increase for a 10-mug/m(3) increment in particulate matter < 10 <mu>m (PM10) lagged 1 day. Conditional on the previous day's asthma symptoms, we estimated 25% (95% CI, 10-42%), 14% (95% CI, 4-26%), and 10% (95% CI, 3-16%) increases in the odds of asthma symptoms associated with increases in CO, PM1.0, and PM10, respectively. We did not find any association between sulfur dioxide (SO2) and the odds of asthma symptoms. In multipollutant models, the separate pollutant effects were smaller. The overall effect of an increase in both CO and PM1.0 was a 31% (95% CI, 11-55%) increase in the odds of symptoms of asthma. We conclude that there is an association between change in shea-term air pollution levels, as indexed by PM and CO, and the occurrence of asthma symptoms among children in Seattle. Although PM effects on asthma have been found in other studies, it is likely that CO is a marker for vehicle exhaust and other combustion by-products that aggravate asthma.. ambient air pollution| asthma| carbon monoxide| children| panel study| particulate matter| sulfur dioxide| symptoms| within-subject effects|respiratory health| particulate matter| longitudinal data| los-angeles| particles| emergency| exposure| visits| time.	DEC-2000	ambient air pollution| asthma| carbon monoxide| children| panel study| particulate matter| sulfur dioxide| symptoms| within-subject effects|respiratory health| particulate matter| longitudinal data| los-angeles| particles| emergency| exposure| visits| time	Yu, OC; Sheppard, L; Lumley, T; Koenig, JQ; Shapiro, GG	Effects of ambient air pollution on symptoms of asthma in Seattle-area children enrolled in the CAMP study		ENVIRONMENTAL HEALTH PERSPECTIVES	ambient air pollution; asthma; carbon monoxide; children; panel study; particulate matter; sulfur dioxide; symptoms; within-subject effects	RESPIRATORY HEALTH; PARTICULATE MATTER; LONGITUDINAL DATA; LOS-ANGELES; PARTICLES; EMERGENCY; EXPOSURE; VISITS; TIME	We observed a panel of 133 children (5-13 years of age) with asthma residing in the greater Seattle, Washington, area for an average of 58 days (range 28-112 days) during screening for enrollment in the Childhood Asthma Management Program (CAMP) study. Daily self-reports of asthma symp toms were obtained from study diaries and compared with ambient air pollution levels in marginal repeated measures logistic regression models. We defined days with asthma symptoms as any day a child reported at least one mild asthma episode. All analyses were controlled for subject-specific variables [age, race, sex, baseline height, and FEV1 PC20 concentration (methacholine provocative concentration required to produce a 20% decrease in forced expiratory volume in 1 sec)] and potential rime-dependent confounders (day of week, season, and temperature). Because of variable observation periods for participants, we estimated both between- and within-subject air pollutant effects. Our primary interest was in the within-subject effects: the effect of air pollutant excursions from typical levels in each child's observation period on the odds of asthma symptoms. In single-pollutant models, the population average estimates indicated a 30% [95% confidence interval (CI), 11-52%] increase for a 1-ppm increment in carbon monoxide lagged I day, an 18% (95% CI, 5-33%) increase for a 10-mug/m(3) increment in same-day particulate matter < 1.0 <mu>m (PM1.0), and an 11% (95% CI, 3-20%) increase for a 10-mug/m(3) increment in particulate matter < 10 <mu>m (PM10) lagged 1 day. Conditional on the previous day's asthma symptoms, we estimated 25% (95% CI, 10-42%), 14% (95% CI, 4-26%), and 10% (95% CI, 3-16%) increases in the odds of asthma symptoms associated with increases in CO, PM1.0, and PM10, respectively. We did not find any association between sulfur dioxide (SO2) and the odds of asthma symptoms. In multipollutant models, the separate pollutant effects were smaller. The overall effect of an increase in both CO and PM1.0 was a 31% (95% CI, 11-55%) increase in the odds of symptoms of asthma. We conclude that there is an association between change in shea-term air pollution levels, as indexed by PM and CO, and the occurrence of asthma symptoms among children in Seattle. Although PM effects on asthma have been found in other studies, it is likely that CO is a marker for vehicle exhaust and other combustion by-products that aggravate asthma.	28	110	2000	6	10.2307/3434835	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Exercise-induced asthma: Is it the right diagnosis in elite athletes?. Exercise-induced asthma, as recognized in asthmatic subjects, is an exaggerated airway response to airway dehydration in the presence of inflammatory cells and their mediators. The airway narrowing is primarily caused by contraction of bronchial smooth muscle. The milder airway narrowing documented in response to exercise in elite athletes and otherwise healthy subjects may simply be the result of the physiologic responses and pathologic changes in airway cells arising from dehydration injury. These changes, which include excessive mucus production and airway edema, would serve both to cause cough and to amplify the narrowing effects of normal bronchial smooth muscle contraction, resulting in symptoms. These changes are more likely to occur in healthy subjects who exercise intensely for long periods of time breathing cold air, dry air, or both. Under these conditions, the ability to humidify inspired air may be overwhelmed, causing significant dehydration of the airway mucosa and an increase in osmolarity, even in small airways. In addition to dehydration injury, airway narrowing to pharmacologic and physical agents may occur as a result of injury caused by large volumes of air containing irritant gases, particulate matter, or allergens being inspired during exercise. As a result, the airways may become inflamed, and the airway smooth muscle may become more sensitive. These events could result in the same exaggerated airway response to dehydration, as documented in asthmatic subjects.. exercise-induced asthma| athletes| dehydration| airway injury| osmolarity|leukotriene-receptor antagonist| neutrophil chemotactic factor| 4.5-percent sodium-chloride| cross-country skiers| induced bronchoconstriction| bronchial hyperresponsiveness| induced bronchospasm| hypertonic saline| mast-cells| cold-air.	SEP-2000	exercise-induced asthma| athletes| dehydration| airway injury| osmolarity|leukotriene-receptor antagonist| neutrophil chemotactic factor| 4.5-percent sodium-chloride| cross-country skiers| induced bronchoconstriction| bronchial hyperresponsiveness| induced bronchospasm| hypertonic saline| mast-cells| cold-air	Anderson, SD; Holzer, K	Exercise-induced asthma: Is it the right diagnosis in elite athletes?		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	exercise-induced asthma; athletes; dehydration; airway injury; osmolarity	LEUKOTRIENE-RECEPTOR ANTAGONIST; NEUTROPHIL CHEMOTACTIC FACTOR; 4.5-PERCENT SODIUM-CHLORIDE; CROSS-COUNTRY SKIERS; INDUCED BRONCHOCONSTRICTION; BRONCHIAL HYPERRESPONSIVENESS; INDUCED BRONCHOSPASM; HYPERTONIC SALINE; MAST-CELLS; COLD-AIR	Exercise-induced asthma, as recognized in asthmatic subjects, is an exaggerated airway response to airway dehydration in the presence of inflammatory cells and their mediators. The airway narrowing is primarily caused by contraction of bronchial smooth muscle. The milder airway narrowing documented in response to exercise in elite athletes and otherwise healthy subjects may simply be the result of the physiologic responses and pathologic changes in airway cells arising from dehydration injury. These changes, which include excessive mucus production and airway edema, would serve both to cause cough and to amplify the narrowing effects of normal bronchial smooth muscle contraction, resulting in symptoms. These changes are more likely to occur in healthy subjects who exercise intensely for long periods of time breathing cold air, dry air, or both. Under these conditions, the ability to humidify inspired air may be overwhelmed, causing significant dehydration of the airway mucosa and an increase in osmolarity, even in small airways. In addition to dehydration injury, airway narrowing to pharmacologic and physical agents may occur as a result of injury caused by large volumes of air containing irritant gases, particulate matter, or allergens being inspired during exercise. As a result, the airways may become inflamed, and the airway smooth muscle may become more sensitive. These events could result in the same exaggerated airway response to dehydration, as documented in asthmatic subjects.	119	110	2000	10	10.1067/mai.2000.108914	Allergy; Immunology
Periostin promotes chronic allergic inflammation in response to Th2 cytokines. Allergic inflammation triggered by exposure of an allergen frequently leads to the onset of chronic inflammatory diseases such as atopic dermatitis (AD) and bronchial asthma. The mechanisms underlying chronicity in allergic inflammation remain unresolved. Periostin, a recently characterized matricellular protein, interacts with several cell surface integrin molecules, providing signals for tissue development and remodeling. Here we show that periostin is a critical mediator for the amplification and persistence of allergic inflammation using a mouse model of skin inflammation. Th2 cytokines IL-4 and IL-13 stimulated fibroblasts to produce periostin, which interacted with alpha(v) integrin, a functional periostin receptor on keratinocytes, inducing production of proinflammatory cytokines, which consequently accelerated Th2-type immune responses. Accordingly, inhibition of periostin or alpha(v) integrin prevented the development or progression of allergen-induced skin inflammation. Thus, periostin sets up a vicious circle that links Th2-type immune responses to keratinocyte activation and plays a critical role in the amplification and chronicity of allergic skin inflammation.. thymic stromal lymphopoietin| nf-kappa-b| atopic-dermatitis| bronchial-asthma| dendritic cells| extracellular-matrix| cancer development| epithelial-cells| mite allergen| tenascin-c.	JUL-2012	thymic stromal lymphopoietin| nf-kappa-b| atopic-dermatitis| bronchial-asthma| dendritic cells| extracellular-matrix| cancer development| epithelial-cells| mite allergen| tenascin-c	Masuoka, M; Shiraishi, H; Ohta, S; Suzuki, S; Arima, K; Aoki, S; Toda, S; Inagaki, N; Kurihara, Y; Hayashida, S; Takeuchi, S; Koike, K; Ono, J; Noshiro, H; Furue, M; Conway, SJ; Narisawa, Y; Izuhara, K	Periostin promotes chronic allergic inflammation in response to Th2 cytokines		JOURNAL OF CLINICAL INVESTIGATION		THYMIC STROMAL LYMPHOPOIETIN; NF-KAPPA-B; ATOPIC-DERMATITIS; BRONCHIAL-ASTHMA; DENDRITIC CELLS; EXTRACELLULAR-MATRIX; CANCER DEVELOPMENT; EPITHELIAL-CELLS; MITE ALLERGEN; TENASCIN-C	Allergic inflammation triggered by exposure of an allergen frequently leads to the onset of chronic inflammatory diseases such as atopic dermatitis (AD) and bronchial asthma. The mechanisms underlying chronicity in allergic inflammation remain unresolved. Periostin, a recently characterized matricellular protein, interacts with several cell surface integrin molecules, providing signals for tissue development and remodeling. Here we show that periostin is a critical mediator for the amplification and persistence of allergic inflammation using a mouse model of skin inflammation. Th2 cytokines IL-4 and IL-13 stimulated fibroblasts to produce periostin, which interacted with alpha(v) integrin, a functional periostin receptor on keratinocytes, inducing production of proinflammatory cytokines, which consequently accelerated Th2-type immune responses. Accordingly, inhibition of periostin or alpha(v) integrin prevented the development or progression of allergen-induced skin inflammation. Thus, periostin sets up a vicious circle that links Th2-type immune responses to keratinocyte activation and plays a critical role in the amplification and chronicity of allergic skin inflammation.	66	109	2012	11	10.1172/JCI58978	Research & Experimental Medicine
Effects of climate change on environmental factors in respiratory allergic diseases. A body of evidence suggests that major changes involving the atmosphere and the climate, including global warming induced by human activity, have an impact on the biosphere and the human environment. Studies on the effects of climate change on respiratory allergy are still lacking and current knowledge is provided by epidemiological and experimental studies on the relationship between asthma and environmental factors, such as meteorological variables, airborne allergens and air pollution. However, there is also considerable evidence that subjects affected by asthma are at an increased risk of developing obstructive airway exacerbations with exposure to gaseous and particulate components of air pollution. It is not easy to evaluate the impact of climate change and air pollution on the prevalence of asthma in general and on the timing of asthma exacerbations. However, the global rise in asthma prevalence and severity suggests that air pollution and climate changes could be contributing. Pollen allergy is frequently used to study the interrelationship between air pollution, rhinitis and bronchial asthma. Epidemiological studies have demonstrated that urbanization, high levels of vehicle emissions and westernized lifestyle are correlated to an increase in the frequency of pollen-induced respiratory allergy, prevalent in people who live in urban areas compared with those who live in rural areas. Meteorological factors (temperature, wind speed, humidity, etc.) along with their climatological regimes (warm or cold anomalies and dry or wet periods, etc.), can affect both biological and chemical components of this interaction. In addition, by inducing airway inflammation, air pollution overcomes the mucosal barrier priming allergen-induced responses. In conclusion, climate change might induce negative effects on respiratory allergic diseases. In particular, the increased length and severity of the pollen season, the higher occurrence of heavy precipitation events and the increasing frequency of urban air pollution episodes suggest that environmental risk factors will have a stronger effect in the following decades.. ragweed ambrosia-artemisiifolia| particulate air-pollution| placebo-controlled trial| grass-pollen| diesel exhaust| hay-fever| childhood asthma| ozone exposure| common ragweed| public-health.	AUG-2008	ragweed ambrosia-artemisiifolia| particulate air-pollution| placebo-controlled trial| grass-pollen| diesel exhaust| hay-fever| childhood asthma| ozone exposure| common ragweed| public-health	D'Amato, G; Cecchi, L	Effects of climate change on environmental factors in respiratory allergic diseases		CLINICAL AND EXPERIMENTAL ALLERGY		RAGWEED AMBROSIA-ARTEMISIIFOLIA; PARTICULATE AIR-POLLUTION; PLACEBO-CONTROLLED TRIAL; GRASS-POLLEN; DIESEL EXHAUST; HAY-FEVER; CHILDHOOD ASTHMA; OZONE EXPOSURE; COMMON RAGWEED; PUBLIC-HEALTH	A body of evidence suggests that major changes involving the atmosphere and the climate, including global warming induced by human activity, have an impact on the biosphere and the human environment. Studies on the effects of climate change on respiratory allergy are still lacking and current knowledge is provided by epidemiological and experimental studies on the relationship between asthma and environmental factors, such as meteorological variables, airborne allergens and air pollution. However, there is also considerable evidence that subjects affected by asthma are at an increased risk of developing obstructive airway exacerbations with exposure to gaseous and particulate components of air pollution. It is not easy to evaluate the impact of climate change and air pollution on the prevalence of asthma in general and on the timing of asthma exacerbations. However, the global rise in asthma prevalence and severity suggests that air pollution and climate changes could be contributing. Pollen allergy is frequently used to study the interrelationship between air pollution, rhinitis and bronchial asthma. Epidemiological studies have demonstrated that urbanization, high levels of vehicle emissions and westernized lifestyle are correlated to an increase in the frequency of pollen-induced respiratory allergy, prevalent in people who live in urban areas compared with those who live in rural areas. Meteorological factors (temperature, wind speed, humidity, etc.) along with their climatological regimes (warm or cold anomalies and dry or wet periods, etc.), can affect both biological and chemical components of this interaction. In addition, by inducing airway inflammation, air pollution overcomes the mucosal barrier priming allergen-induced responses. In conclusion, climate change might induce negative effects on respiratory allergic diseases. In particular, the increased length and severity of the pollen season, the higher occurrence of heavy precipitation events and the increasing frequency of urban air pollution episodes suggest that environmental risk factors will have a stronger effect in the following decades.	120	109	2008	11	10.1111/j.1365-2222.2008.03033.x	Allergy; Immunology
Importance of oxidative stress in the pathogenesis and treatment of asthma. Purpose of review The purpose of the current review is to summarize recent evidence demonstrating the important role of oxidative stress in asthma pathogenesis. The therapeutic implications of these findings will be presented. Recent findings Mechanistically, the effect of oxidative stress on dendritic cells has been demonstrated to have a potent effect on Th1/Th2 skewing of the immune response. Investigations of gene-environment interactions have identified genetic polymorphisms associated with individual susceptibility to poll utant-ind uced respiratory oxidative stress. The effects of current asthma therapy on oxidative stress are currently unclear, but previous trials using conventional antioxidant therapy in asthma have been largely ineffective. Recent investigations have identified two promising broad-based therapeutic approaches: Nrf2 pathway activation and the use of thiol precursors. Preliminary data suggest that fullerene nanomaterials and dietary interventions may also have potential benefits in asthma. Summary Our current understanding of the role of oxidative stress in asthma suggests that antioxidant therapy may be important in optimizing asthma treatment and prevention. The future success of antioxidant asthma therapy will require strategies with broad effects on airway redox equilibrium and the selection of appropriate target populations.. air pollution| antioxidants| asthma| genetic polymorphisms| oxidative stress|diesel exhaust particles| placebo-controlled trial| airway epithelial-cells| gene polymorphisms| allergic responses| respiratory health| n-acetylcysteine| nasal challenge| risk-factors| vitamin-c.	FEB-2008	air pollution| antioxidants| asthma| genetic polymorphisms| oxidative stress|diesel exhaust particles| placebo-controlled trial| airway epithelial-cells| gene polymorphisms| allergic responses| respiratory health| n-acetylcysteine| nasal challenge| risk-factors| vitamin-c	Riedl, MA; Nel, AE	Importance of oxidative stress in the pathogenesis and treatment of asthma		CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY	air pollution; antioxidants; asthma; genetic polymorphisms; oxidative stress	DIESEL EXHAUST PARTICLES; PLACEBO-CONTROLLED TRIAL; AIRWAY EPITHELIAL-CELLS; GENE POLYMORPHISMS; ALLERGIC RESPONSES; RESPIRATORY HEALTH; N-ACETYLCYSTEINE; NASAL CHALLENGE; RISK-FACTORS; VITAMIN-C	Purpose of review The purpose of the current review is to summarize recent evidence demonstrating the important role of oxidative stress in asthma pathogenesis. The therapeutic implications of these findings will be presented. Recent findings Mechanistically, the effect of oxidative stress on dendritic cells has been demonstrated to have a potent effect on Th1/Th2 skewing of the immune response. Investigations of gene-environment interactions have identified genetic polymorphisms associated with individual susceptibility to poll utant-ind uced respiratory oxidative stress. The effects of current asthma therapy on oxidative stress are currently unclear, but previous trials using conventional antioxidant therapy in asthma have been largely ineffective. Recent investigations have identified two promising broad-based therapeutic approaches: Nrf2 pathway activation and the use of thiol precursors. Preliminary data suggest that fullerene nanomaterials and dietary interventions may also have potential benefits in asthma. Summary Our current understanding of the role of oxidative stress in asthma suggests that antioxidant therapy may be important in optimizing asthma treatment and prevention. The future success of antioxidant asthma therapy will require strategies with broad effects on airway redox equilibrium and the selection of appropriate target populations.	59	109	2008	8		Allergy; Immunology
Mode of delivery - Effects on gut microbiota and humoral immunity. Background: The rate of caesarean deliveries has increased 10-fold worldwide during the past decades. Objective: To evaluate differences in the establishment of gut microbiota in infants born by vaginal or caesarean delivery and its impact on mucosal immunity. Methods: Altogether, 165 consecutive children, prospectively followed from birth at our clinic in Turku, Finland, were gathered; 141 (85%) were born by vaginal delivery and 24 (15%) by caesarean section. Blood was drawn at physician visits for indirect evaluation of mucosal immunity by ELISPOT assay. Faecal samples were obtained for determination of the gut microbiota by fluorescence in situ hybridization of bacterial cells. Results: Infants delivered by caesarean section harboured fewer bifidobacteria at an early age and were shown to mount a stronger humoral immune response. At 1 month of age, the total gut bacterial cell counts per 1 g faeces were higher in vaginally delivered infants (9.9 x 10(9), 95% CI 7.9 x 10(9)-1.2 x 10(10)) as compared to caesarean section delivered (3.1 x 10(9), 95% CI 1.1 x 10(9)-8.6 x 10(9)) (p = 0.001). This distinction was mainly due to the greater number of bifidobacteria in vaginally delivered infants (1.9 x 10(9), 95% CI 6.3 x 10(8)-5.6 x 10(9) vs. 1.5 x 10(6), 95% CI 4.1 x 10(2)-5.7 x 10(9), respectively) (p = 0.001). During the first year of life, the total number of IgA-, IgG- and IgM-secreting cells was lower (p = 0.03, p = 0.02, p = 0.11, respectively) in infants born by vaginal delivery than in those born by caesarean section, possibly reflecting excessive antigen exposure across the vulnerable gut barrier. Conclusions: Our findings demonstrate that the mode of delivery may have, possibly via gut microbiota development, significant effects on immunological functions in the infant (http://www.clinicaltrials.gov/ct/gui/show/NCT00167700). Copyright (C) 2007 S. Karger AG, Basel.. caesarean section| vaginal delivery| gut microbiota| humoral immunity|in-situ hybridization| atopic-dermatitis| blood-lymphocytes| children| infants| bacteria| allergy| probes| identification| microflora.	2008	caesarean section| vaginal delivery| gut microbiota| humoral immunity|in-situ hybridization| atopic-dermatitis| blood-lymphocytes| children| infants| bacteria| allergy| probes| identification| microflora	Huurre, A; Kalliomaki, M; Rautava, S; Rinne, M; Salminen, S; Isolauri, E	Mode of delivery - Effects on gut microbiota and humoral immunity		NEONATOLOGY	caesarean section; vaginal delivery; gut microbiota; humoral immunity	IN-SITU HYBRIDIZATION; ATOPIC-DERMATITIS; BLOOD-LYMPHOCYTES; CHILDREN; INFANTS; BACTERIA; ALLERGY; PROBES; IDENTIFICATION; MICROFLORA	Background: The rate of caesarean deliveries has increased 10-fold worldwide during the past decades. Objective: To evaluate differences in the establishment of gut microbiota in infants born by vaginal or caesarean delivery and its impact on mucosal immunity. Methods: Altogether, 165 consecutive children, prospectively followed from birth at our clinic in Turku, Finland, were gathered; 141 (85%) were born by vaginal delivery and 24 (15%) by caesarean section. Blood was drawn at physician visits for indirect evaluation of mucosal immunity by ELISPOT assay. Faecal samples were obtained for determination of the gut microbiota by fluorescence in situ hybridization of bacterial cells. Results: Infants delivered by caesarean section harboured fewer bifidobacteria at an early age and were shown to mount a stronger humoral immune response. At 1 month of age, the total gut bacterial cell counts per 1 g faeces were higher in vaginally delivered infants (9.9 x 10(9), 95% CI 7.9 x 10(9)-1.2 x 10(10)) as compared to caesarean section delivered (3.1 x 10(9), 95% CI 1.1 x 10(9)-8.6 x 10(9)) (p = 0.001). This distinction was mainly due to the greater number of bifidobacteria in vaginally delivered infants (1.9 x 10(9), 95% CI 6.3 x 10(8)-5.6 x 10(9) vs. 1.5 x 10(6), 95% CI 4.1 x 10(2)-5.7 x 10(9), respectively) (p = 0.001). During the first year of life, the total number of IgA-, IgG- and IgM-secreting cells was lower (p = 0.03, p = 0.02, p = 0.11, respectively) in infants born by vaginal delivery than in those born by caesarean section, possibly reflecting excessive antigen exposure across the vulnerable gut barrier. Conclusions: Our findings demonstrate that the mode of delivery may have, possibly via gut microbiota development, significant effects on immunological functions in the infant (http://www.clinicaltrials.gov/ct/gui/show/NCT00167700). Copyright (C) 2007 S. Karger AG, Basel.	22	109	2008	5	10.1159/000111102	Pediatrics
Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma. Allergic asthma is characterized by airway inflammation initiated by adaptive immune responses to aeroallergens. Recent data suggest that severe asthma may be a different form of asthma rather than an increase in asthma symptoms and that innate immune responses to LPS can modulate adaptive immune responses to allergens. In this study, we evaluated the hypothesis that airway exposure to different doses of LPS induces different form of asthma. Our study showed that neutrophilic inflammation and IFN-gamma expression were higher in induced sputum from severe asthma patients than from mild to moderate asthmatics. Animal experiments indicated that allergen sensitization with low-dose LPS (0.1 mu g) induced type 2 asthma phenotypes, i.e., airway hyper-responsiveness, eosinophilic inflammation, and allergen-specific IgE up-regulation. In contrast, allergen sensitization with high-dose LPS (10 mu g) induced asthma phenotypes, i.e., airway hyperresponsiveness and noneosinophilic inflammation that were not developed in IFN-gamma-deficient mice, but unaffected in the absence of IL-4. During the allergen sensitization period, TNF-alpha expression was found to be enhanced by both low- and high-dose LPS, whereas IL-12 expression was only enhanced by high-dose LPS. Interestingly, the asthma phenotypes induced by low-dose LPS, but not by high-dose LPS, were completely inhibited in TNF-a receptor-deficient mice, whereas the asthma phenotypes induced by high-dose LPS were abolished in the homozygous null mutation of the STAT4 gene. These findings suggest that airway exposure levels of LPS induces different forms of asthma that are type 1 and type 2 asthma phenotypes by high and low LPS levels, respectively.. house-dust endotoxin| t-cell development| interferon-gamma| dendritic cells| allergic-asthma| responses| mice| hyperresponsiveness| inflammation| antigen.	APR 15-2007	house-dust endotoxin| t-cell development| interferon-gamma| dendritic cells| allergic-asthma| responses| mice| hyperresponsiveness| inflammation| antigen	Kim, YK; Oh, SY; Jeon, SG; Park, HW; Lee, SY; Chun, EY; Bang, B; Lee, HS; Oh, MH; Kim, YS; Kim, JH; Gho, YS; Cho, SH; Min, KU; Kim, YY; Zhu, Z	Airway exposure levels of lipopolysaccharide determine type 1 versus type 2 experimental asthma		JOURNAL OF IMMUNOLOGY		HOUSE-DUST ENDOTOXIN; T-CELL DEVELOPMENT; INTERFERON-GAMMA; DENDRITIC CELLS; ALLERGIC-ASTHMA; RESPONSES; MICE; HYPERRESPONSIVENESS; INFLAMMATION; ANTIGEN	Allergic asthma is characterized by airway inflammation initiated by adaptive immune responses to aeroallergens. Recent data suggest that severe asthma may be a different form of asthma rather than an increase in asthma symptoms and that innate immune responses to LPS can modulate adaptive immune responses to allergens. In this study, we evaluated the hypothesis that airway exposure to different doses of LPS induces different form of asthma. Our study showed that neutrophilic inflammation and IFN-gamma expression were higher in induced sputum from severe asthma patients than from mild to moderate asthmatics. Animal experiments indicated that allergen sensitization with low-dose LPS (0.1 mu g) induced type 2 asthma phenotypes, i.e., airway hyper-responsiveness, eosinophilic inflammation, and allergen-specific IgE up-regulation. In contrast, allergen sensitization with high-dose LPS (10 mu g) induced asthma phenotypes, i.e., airway hyperresponsiveness and noneosinophilic inflammation that were not developed in IFN-gamma-deficient mice, but unaffected in the absence of IL-4. During the allergen sensitization period, TNF-alpha expression was found to be enhanced by both low- and high-dose LPS, whereas IL-12 expression was only enhanced by high-dose LPS. Interestingly, the asthma phenotypes induced by low-dose LPS, but not by high-dose LPS, were completely inhibited in TNF-a receptor-deficient mice, whereas the asthma phenotypes induced by high-dose LPS were abolished in the homozygous null mutation of the STAT4 gene. These findings suggest that airway exposure levels of LPS induces different forms of asthma that are type 1 and type 2 asthma phenotypes by high and low LPS levels, respectively.	45	109	2007	8		Immunology
"Parental smoking and children's respiratory health: independent effects of prenatal and postnatal exposure. Objectives: Adverse effects have been reported of prenatal and/or postnatal passive exposure to smoking on children's health. Uncertainties remain about the relative importance of smoking at different periods in the child's life. We investigate this in a pooled analysis, on 53 879 children from 12 cross-sectional studies-components of the PATY study (Pollution And The Young). Methods: Effects were estimated, within each study, of three exposures: mother smoked during pregnancy, parental smoking in the first two years, current parental smoking. Outcomes were: wheeze, asthma, ""woken by wheeze'', bronchitis, nocturnal cough, morning cough, ""sensitivity to inhaled allergens'' and hay fever. Logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results, and mean effects (allowing for heterogeneity) were estimated using meta-analytical tools. Results: There was strong evidence linking parental smoking to wheeze, asthma, bronchitis and nocturnal cough, with mean odds ratios all around 1.15, with independent effects of prenatal and postnatal exposures for most associations. Conclusions: Adverse effects of both pre- and postnatal parental smoking on children's respiratory health were confirmed. Asthma was most strongly associated with maternal smoking during pregnancy, but postnatal exposure showed independent associations with a range of other respiratory symptoms. All tobacco smoke exposure has serious consequences for children's respiratory health and needs to be reduced urgently.. environmental tobacco-smoke| maternal smoking| lung-function| childhood asthma| passive smoking| air-pollution| birth-weight| in-utero| symptoms| pregnancy."	AUG-2006	environmental tobacco-smoke| maternal smoking| lung-function| childhood asthma| passive smoking| air-pollution| birth-weight| in-utero| symptoms| pregnancy	Pattenden, S; Antova, T; Neuberger, M; Nikiforov, B; De Sario, M; Grize, L; Heinrich, J; Hruba, F; Janssen, N; Luttmann-Gibson, H; Privalova, L; Rudnai, P; Splichalova, A; Zlotkowska, R; Fletcher, T	Parental smoking and children's respiratory health: independent effects of prenatal and postnatal exposure		TOBACCO CONTROL		ENVIRONMENTAL TOBACCO-SMOKE; MATERNAL SMOKING; LUNG-FUNCTION; CHILDHOOD ASTHMA; PASSIVE SMOKING; AIR-POLLUTION; BIRTH-WEIGHT; IN-UTERO; SYMPTOMS; PREGNANCY	"Objectives: Adverse effects have been reported of prenatal and/or postnatal passive exposure to smoking on children's health. Uncertainties remain about the relative importance of smoking at different periods in the child's life. We investigate this in a pooled analysis, on 53 879 children from 12 cross-sectional studies-components of the PATY study (Pollution And The Young). Methods: Effects were estimated, within each study, of three exposures: mother smoked during pregnancy, parental smoking in the first two years, current parental smoking. Outcomes were: wheeze, asthma, ""woken by wheeze'', bronchitis, nocturnal cough, morning cough, ""sensitivity to inhaled allergens'' and hay fever. Logistic regressions were used, controlling for individual risk factors and study area. Heterogeneity between study-specific results, and mean effects (allowing for heterogeneity) were estimated using meta-analytical tools. Results: There was strong evidence linking parental smoking to wheeze, asthma, bronchitis and nocturnal cough, with mean odds ratios all around 1.15, with independent effects of prenatal and postnatal exposures for most associations. Conclusions: Adverse effects of both pre- and postnatal parental smoking on children's respiratory health were confirmed. Asthma was most strongly associated with maternal smoking during pregnancy, but postnatal exposure showed independent associations with a range of other respiratory symptoms. All tobacco smoke exposure has serious consequences for children's respiratory health and needs to be reduced urgently."	40	109	2006	8	10.1136/tc.2005.015065	Public, Environmental & Occupational Health
Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma. Background Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found. Objective To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma. Methods Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges. Results Prenatal, maternal LPS-exposure enhanced neonatal IFN-gamma, but not IL-4 and IL-2 production. OVA sensitization of prenatally LPS-exposed mice was accompanied by a marked suppression in anti-OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL-5 and IL-13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper-responsiveness, a hallmark of bronchial asthma, was not affected. Conclusion This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.. airway inflammation| allergy| immune response| lipopolysaccharide| materno-fetal interaction| mice| th1/th-2|hay-fever| atopic disease| house-dust| t-cells| endotoxin| children| hyperresponsiveness| hyperreactivity| prevalence| antibodies.	MAR-2005	airway inflammation| allergy| immune response| lipopolysaccharide| materno-fetal interaction| mice| th1/th-2|hay-fever| atopic disease| house-dust| t-cells| endotoxin| children| hyperresponsiveness| hyperreactivity| prevalence| antibodies	Blumer, N; Herz, U; Wegmann, M; Renz, H	Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma		CLINICAL AND EXPERIMENTAL ALLERGY	airway inflammation; allergy; immune response; lipopolysaccharide; materno-fetal interaction; mice; Th1/Th-2	HAY-FEVER; ATOPIC DISEASE; HOUSE-DUST; T-CELLS; ENDOTOXIN; CHILDREN; HYPERRESPONSIVENESS; HYPERREACTIVITY; PREVALENCE; ANTIBODIES	Background Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found. Objective To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma. Methods Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges. Results Prenatal, maternal LPS-exposure enhanced neonatal IFN-gamma, but not IL-4 and IL-2 production. OVA sensitization of prenatally LPS-exposed mice was accompanied by a marked suppression in anti-OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL-5 and IL-13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper-responsiveness, a hallmark of bronchial asthma, was not affected. Conclusion This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.	31	109	2005	6	10.1111/j.1365-2222.2005.02184.x	Allergy; Immunology
An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population. Background The prevalence of atopic diseases has been increasing in developed countries. This could be explained by the hygiene hypothesis, which states that exposure to specific infections or endotoxins during infancy drives the maturing immune system towards a Th1 phenotype and away from the Th2 phenotype, which is associated with allergic diseases. Toll-like receptors (TLRs) play important roles in the signalling of many pathogen-related molecules and endogenous proteins associated with immune activation. Objective The aim of the present study was to investigate whether polymorphisms in genes encoding TLRs are associated with asthma or total serum IgE levels. Methods We screened the 5' flanking and coding regions of the TLR2,TLR3, TLR4, and TLR9 genes for polymorphisms by direct sequencing of DNA from 32 asthmatics, and analysed the effect of the polymorphisms on the development of atopic asthma and on total serum IgE levels. Results We identified 16 variants in TLRs. The transmission disequilibrium test of the families revealed that none of the alleles or haplotypes were associated with asthma or total IgE levels (P>0.05). However, we found an insertion/deletion polymorphism in the 5' untranslated region of TLR2, and an expression construct containing the deletion allele showed lower luciferase activity than the wild-type alleles, suggesting that the deletion allele has reduced transcriptional activity. Conclusion Our results indicate that polymorphisms in TLRs are not likely to be associated with the development of atopy-related phenotypes in a Japanese population.. asthma| ige| polymorphism| tdt| toll-like receptor|pattern-recognition| transcriptional regulation| linkage disequilibrium| activation| gene| prevalence| haplotypes| mutations| endotoxin| symptoms.	FEB-2004	asthma| ige| polymorphism| tdt| toll-like receptor|pattern-recognition| transcriptional regulation| linkage disequilibrium| activation| gene| prevalence| haplotypes| mutations| endotoxin| symptoms	Noguchi, E; Nishimura, F; Fukai, H; Kim, J; Ichikawa, K; Shibasaki, M; Arinami, T	An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; IgE; polymorphism; TDT; Toll-like receptor	PATTERN-RECOGNITION; TRANSCRIPTIONAL REGULATION; LINKAGE DISEQUILIBRIUM; ACTIVATION; GENE; PREVALENCE; HAPLOTYPES; MUTATIONS; ENDOTOXIN; SYMPTOMS	Background The prevalence of atopic diseases has been increasing in developed countries. This could be explained by the hygiene hypothesis, which states that exposure to specific infections or endotoxins during infancy drives the maturing immune system towards a Th1 phenotype and away from the Th2 phenotype, which is associated with allergic diseases. Toll-like receptors (TLRs) play important roles in the signalling of many pathogen-related molecules and endogenous proteins associated with immune activation. Objective The aim of the present study was to investigate whether polymorphisms in genes encoding TLRs are associated with asthma or total serum IgE levels. Methods We screened the 5' flanking and coding regions of the TLR2,TLR3, TLR4, and TLR9 genes for polymorphisms by direct sequencing of DNA from 32 asthmatics, and analysed the effect of the polymorphisms on the development of atopic asthma and on total serum IgE levels. Results We identified 16 variants in TLRs. The transmission disequilibrium test of the families revealed that none of the alleles or haplotypes were associated with asthma or total IgE levels (P>0.05). However, we found an insertion/deletion polymorphism in the 5' untranslated region of TLR2, and an expression construct containing the deletion allele showed lower luciferase activity than the wild-type alleles, suggesting that the deletion allele has reduced transcriptional activity. Conclusion Our results indicate that polymorphisms in TLRs are not likely to be associated with the development of atopy-related phenotypes in a Japanese population.	35	109	2004	7	10.1111/j.1365-2222.2004.01839.x	Allergy; Immunology
Traffic related air pollution and incidence of childhood asthma: results of the Vesta case-control study. Study objective: The Vesta project aims to assess the role of traffic related air pollution in the occurrence of childhood asthma. Design and setting: Case- control study conducted in five French metropolitan areas between 1998 and 2000. A set of 217 pairs of matched 4 to 14 years old cases and controls were investigated. An index of lifelong exposure to traffic exhausts was constructed, using retrospective information on traffic density close to all home and school addresses since birth; this index was also calculated for the 0 - 3 years age period to investigate the effect of early exposures. Main results: Adjusted on environmental tobacco smoke, personal and parental allergy, and several confounders, lifelong exposure was not associated with asthma. In contrast, associations before age of 3 were significant: odds ratios for tertiles 2 and 3 of the exposure index, relative to tertile 1, exhibited a positive trend ( 1.48 ( 95% CI = 0.7 to 3.0) and 2.28 ( 1.1 to 4.6)), with greater odds ratios among subjects with positive skin prick tests. Conclusions: These results suggest that traffic related pollutants might have contributed to the asthma epidemic that has taken place during the past decades among children.. diesel exhaust| respiratory health| east-germany| in-vivo| children| exposure| association| prevalence| immunology| residence.	JAN-2004	diesel exhaust| respiratory health| east-germany| in-vivo| children| exposure| association| prevalence| immunology| residence	Zmirou, D; Gauvin, S; Pin, I; Momas, I; Sahraoui, F; Just, J; Le Moullec, Y; Bremont, F; Cassadou, S; Reungoat, P; Albertini, M; Lauvergne, N; Chiron, M; Labbe, A	Traffic related air pollution and incidence of childhood asthma: results of the Vesta case-control study		JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH		DIESEL EXHAUST; RESPIRATORY HEALTH; EAST-GERMANY; IN-VIVO; CHILDREN; EXPOSURE; ASSOCIATION; PREVALENCE; IMMUNOLOGY; RESIDENCE	Study objective: The Vesta project aims to assess the role of traffic related air pollution in the occurrence of childhood asthma. Design and setting: Case- control study conducted in five French metropolitan areas between 1998 and 2000. A set of 217 pairs of matched 4 to 14 years old cases and controls were investigated. An index of lifelong exposure to traffic exhausts was constructed, using retrospective information on traffic density close to all home and school addresses since birth; this index was also calculated for the 0 - 3 years age period to investigate the effect of early exposures. Main results: Adjusted on environmental tobacco smoke, personal and parental allergy, and several confounders, lifelong exposure was not associated with asthma. In contrast, associations before age of 3 were significant: odds ratios for tertiles 2 and 3 of the exposure index, relative to tertile 1, exhibited a positive trend ( 1.48 ( 95% CI = 0.7 to 3.0) and 2.28 ( 1.1 to 4.6)), with greater odds ratios among subjects with positive skin prick tests. Conclusions: These results suggest that traffic related pollutants might have contributed to the asthma epidemic that has taken place during the past decades among children.	43	109	2004	6	10.1136/jech.58.1.18	Public, Environmental & Occupational Health
Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations. Background: Early exposure to microbial matter such as LPS may influence the development of asthma and allergies by activation of innate immunity pathways as indicated by studies in farming environments. Recently, polymorphisms in caspase recruitment domain containing protein 15 (CARD15), an intracellular LPS receptor protein, have been associated with Crohn's disease. Because these polymorphisms lead to changes in LPS recognition, they may affect the development of asthma and allergies. Objective: We genotyped a large population of German schoolchildren (N = 1872) from East and West Germany for 3 functional relevant CARD15 polymorphisms for their role in the development of asthma and allergy. Methods: By use of parental questionnaires, skin prick testing, pulmonary function tests, bronchial challenge tests, and measurements of serum IgE levels, children were phenotyped for the presence of atopic diseases. Genotyping was performed with PCR-based restriction enzyme assays. To assess associations between atopic phenotypes and genotypes standard statistical procedures were applied. Results: Children with the polymorphic allele C2722 had a more than 3-fold risk to develop allergic rhinitis (P < .001) and an almost 2-fold risk for atopic dermatitis (P < .05). Furthermore, the T2104 allele was associated with an almost 2-fold risk for allergic rhinitis (P < .05). When a C insertion at position 3020 was present, the risk of atopy increased by 50% (P < .05) and serum IgE levels were elevated (P < .01). Conclusion: The shared genetic background between Crohn's disease and atopy may indicate that an impaired recognition of microbial exposures results in an insufficient downregulation of excessive immune responses, giving rise to either T(H)2 dominated allergies or T(H)1 related Crohn's disease.. asthma| atopic dermatitis| allergic rhinitis| atopy| childhood| ige| card15| nod2| polymorphism| snp|crohns-disease| kappa-b| nod2| susceptibility| monocytes| mutation| gene.	APR-2003	asthma| atopic dermatitis| allergic rhinitis| atopy| childhood| ige| card15| nod2| polymorphism| snp|crohns-disease| kappa-b| nod2| susceptibility| monocytes| mutation| gene	Kabesch, M; Peters, W; Carr, D; Leupold, W; Weiland, SK; von Mutius, E	Association between polymorphisms in caspase recruitment domain containing protein 15 and allergy in two German populations		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; atopic dermatitis; allergic rhinitis; atopy; childhood; IgE; CARD15; NOD2; polymorphism; SNP	CROHNS-DISEASE; KAPPA-B; NOD2; SUSCEPTIBILITY; MONOCYTES; MUTATION; GENE	Background: Early exposure to microbial matter such as LPS may influence the development of asthma and allergies by activation of innate immunity pathways as indicated by studies in farming environments. Recently, polymorphisms in caspase recruitment domain containing protein 15 (CARD15), an intracellular LPS receptor protein, have been associated with Crohn's disease. Because these polymorphisms lead to changes in LPS recognition, they may affect the development of asthma and allergies. Objective: We genotyped a large population of German schoolchildren (N = 1872) from East and West Germany for 3 functional relevant CARD15 polymorphisms for their role in the development of asthma and allergy. Methods: By use of parental questionnaires, skin prick testing, pulmonary function tests, bronchial challenge tests, and measurements of serum IgE levels, children were phenotyped for the presence of atopic diseases. Genotyping was performed with PCR-based restriction enzyme assays. To assess associations between atopic phenotypes and genotypes standard statistical procedures were applied. Results: Children with the polymorphic allele C2722 had a more than 3-fold risk to develop allergic rhinitis (P < .001) and an almost 2-fold risk for atopic dermatitis (P < .05). Furthermore, the T2104 allele was associated with an almost 2-fold risk for allergic rhinitis (P < .05). When a C insertion at position 3020 was present, the risk of atopy increased by 50% (P < .05) and serum IgE levels were elevated (P < .01). Conclusion: The shared genetic background between Crohn's disease and atopy may indicate that an impaired recognition of microbial exposures results in an insufficient downregulation of excessive immune responses, giving rise to either T(H)2 dominated allergies or T(H)1 related Crohn's disease.	16	109	2003	5	10.1067/mai.2003.1336	Allergy; Immunology
Pathogenesis-related (PR)-proteins identified as allergens. Type I allergies are recognized as an important disease affecting around 25 % of the population of industrialized countries of the Northern hemisphere. Allergic patients produce specific IgE antibodies after frequent exposure to either inhaled or nutritive allergens. Of the plant allergens listed in the Official Allergen Database of the International Union of Immunological Societies, approx. 25 % belong to the group of pathogenesis-related proteins (PR-proteins). PR-proteins are defined as proteins that are induced upon stress, pathogen attack and abiotic stimuli. This inhomogeneous group of proteins has been classified into 14 PR-protein families. So far, plant-derived allergens have been identified with sequence similarities to PR-protein families 2, 3, 4, 5, 8, 10 and 14. In general, both protein groups, i.e. PR-proteins and allergens, comprise rather small proteins, which are stable at low pH and resistant to proteolysis. These features, and their level of expression, make PR-proteins good candidates for evoking an immune response in predisposed humans, when coming into contact with mucosal surfaces. The identification of PR-proteins with allergenic potential and their homologues is of importance for the allergic patient and the management of this disease. Firstly, plant foods derived from genetically modified plants could represent new allergen sources, and therefore should be evaluated carefully for their potential allergenicity. Secondly, complex plant-derived foods should be analysed for hidden allergens and labelled accordingly.. chitinase| ige| latex| lipid transfer protein| pathogenesis-related protein| plant allergens|lipid transfer protein| peach prunus-persica| amino-acid-sequence| class-i chitinases| major allergen| molecular characterization| pollen allergens| rosaceae fruits| pr proteins| expression.	NOV-2002	chitinase| ige| latex| lipid transfer protein| pathogenesis-related protein| plant allergens|lipid transfer protein| peach prunus-persica| amino-acid-sequence| class-i chitinases| major allergen| molecular characterization| pollen allergens| rosaceae fruits| pr proteins| expression	Hoffmann-Sommergruber, K	Pathogenesis-related (PR)-proteins identified as allergens		BIOCHEMICAL SOCIETY TRANSACTIONS	chitinase; IgE; latex; lipid transfer protein; pathogenesis-related protein; plant allergens	LIPID TRANSFER PROTEIN; PEACH PRUNUS-PERSICA; AMINO-ACID-SEQUENCE; CLASS-I CHITINASES; MAJOR ALLERGEN; MOLECULAR CHARACTERIZATION; POLLEN ALLERGENS; ROSACEAE FRUITS; PR PROTEINS; EXPRESSION	Type I allergies are recognized as an important disease affecting around 25 % of the population of industrialized countries of the Northern hemisphere. Allergic patients produce specific IgE antibodies after frequent exposure to either inhaled or nutritive allergens. Of the plant allergens listed in the Official Allergen Database of the International Union of Immunological Societies, approx. 25 % belong to the group of pathogenesis-related proteins (PR-proteins). PR-proteins are defined as proteins that are induced upon stress, pathogen attack and abiotic stimuli. This inhomogeneous group of proteins has been classified into 14 PR-protein families. So far, plant-derived allergens have been identified with sequence similarities to PR-protein families 2, 3, 4, 5, 8, 10 and 14. In general, both protein groups, i.e. PR-proteins and allergens, comprise rather small proteins, which are stable at low pH and resistant to proteolysis. These features, and their level of expression, make PR-proteins good candidates for evoking an immune response in predisposed humans, when coming into contact with mucosal surfaces. The identification of PR-proteins with allergenic potential and their homologues is of importance for the allergic patient and the management of this disease. Firstly, plant foods derived from genetically modified plants could represent new allergen sources, and therefore should be evaluated carefully for their potential allergenicity. Secondly, complex plant-derived foods should be analysed for hidden allergens and labelled accordingly.	52	109	2002	6	10.1042/BST0300930	Biochemistry & Molecular Biology
Exposure and respiratory health in farming in temperate zones - A review of the literature. To review studies in farming populations from temperate zones focusing on: (1) exposure to dust, bacteria, moulds, endotoxin, and ammonia, (2) sensitisation to common airborne allergens, (3) prevalence, incidence and risk factors of chronic bronchitis, asthma and bronchial hyperresponsiveness, and (4) measurements of lung function. Working in animal housings can be associated with exposure to organic dust, bacteria, moulds, endotoxin, and ammonia in concentrations that can induce cellular and immunological responses and result in respiratory diseases. Working in poultry housing might be associated with higher exposures to dust, bacteria, and ammonia than in swine and cow housings, and endotoxin exposure seems to be higher in North America than in Europe. Working exposure might influence the domestic area on farms, and there might be a protective effect of being raised on a farm regarding sensitisation and allergic diseases. Sensitisation to mites seems to be the most prevalent of the common inhalant allergens. Chronic bronchitis is frequent and data suggests that it is work related in farmers. Findings concerning asthma are less uniform, and data regarding bronchial hyperresponsiveness are too sparse and inconsistent to evaluate the effect on farming. Several risk factors have been described, and age is shared for all three clinical manifestations, while male gender, atopy, smoking, pig farming, and animal production are common risk factors for chronic bronchitis and asthma. FEV1, and FEV1/FVC seems to be reduced in farmers, and longitudinal studies indicate an increased annual loss in FEV1 in farmers, especially in pig farmers. The increased annual decline has been associated with lung function, bronchial hyperresponsiveness, smoking, automatic dry feeding systems, and endotoxin. Despite studies with methodological weaknesses, heterogenity in sampling times, measurement techniques, equipment, and diagnostic criteria, the review has revealed that the exposure to organic dust in farming can be substantial and might lead to respiratory diseases and increased annual loss in lung function. Working exposure seems to influence the domestic area in farms, and being raised on a farm might have a protective effect regarding sensitisation and allergic diseases.. farming| agriculture| temperate zones| confinement buildings| measurements| exposure| sensitisation| asthma| chronic bronchitis| bronchial responsiveness| lung function|swine-confinement buildings| dose-response relationships| cross-sectional survey| lung-function decline| new-zealand farmers| chronic-bronchitis| dairy farmers| pig farmers| storage mites| risk-factors.	2002	farming| agriculture| temperate zones| confinement buildings| measurements| exposure| sensitisation| asthma| chronic bronchitis| bronchial responsiveness| lung function|swine-confinement buildings| dose-response relationships| cross-sectional survey| lung-function decline| new-zealand farmers| chronic-bronchitis| dairy farmers| pig farmers| storage mites| risk-factors	Omland, O	Exposure and respiratory health in farming in temperate zones - A review of the literature		ANNALS OF AGRICULTURAL AND ENVIRONMENTAL MEDICINE	farming; agriculture; temperate zones; confinement buildings; measurements; exposure; sensitisation; asthma; chronic bronchitis; bronchial responsiveness; lung function	SWINE-CONFINEMENT BUILDINGS; DOSE-RESPONSE RELATIONSHIPS; CROSS-SECTIONAL SURVEY; LUNG-FUNCTION DECLINE; NEW-ZEALAND FARMERS; CHRONIC-BRONCHITIS; DAIRY FARMERS; PIG FARMERS; STORAGE MITES; RISK-FACTORS	To review studies in farming populations from temperate zones focusing on: (1) exposure to dust, bacteria, moulds, endotoxin, and ammonia, (2) sensitisation to common airborne allergens, (3) prevalence, incidence and risk factors of chronic bronchitis, asthma and bronchial hyperresponsiveness, and (4) measurements of lung function. Working in animal housings can be associated with exposure to organic dust, bacteria, moulds, endotoxin, and ammonia in concentrations that can induce cellular and immunological responses and result in respiratory diseases. Working in poultry housing might be associated with higher exposures to dust, bacteria, and ammonia than in swine and cow housings, and endotoxin exposure seems to be higher in North America than in Europe. Working exposure might influence the domestic area on farms, and there might be a protective effect of being raised on a farm regarding sensitisation and allergic diseases. Sensitisation to mites seems to be the most prevalent of the common inhalant allergens. Chronic bronchitis is frequent and data suggests that it is work related in farmers. Findings concerning asthma are less uniform, and data regarding bronchial hyperresponsiveness are too sparse and inconsistent to evaluate the effect on farming. Several risk factors have been described, and age is shared for all three clinical manifestations, while male gender, atopy, smoking, pig farming, and animal production are common risk factors for chronic bronchitis and asthma. FEV1, and FEV1/FVC seems to be reduced in farmers, and longitudinal studies indicate an increased annual loss in FEV1 in farmers, especially in pig farmers. The increased annual decline has been associated with lung function, bronchial hyperresponsiveness, smoking, automatic dry feeding systems, and endotoxin. Despite studies with methodological weaknesses, heterogenity in sampling times, measurement techniques, equipment, and diagnostic criteria, the review has revealed that the exposure to organic dust in farming can be substantial and might lead to respiratory diseases and increased annual loss in lung function. Working exposure seems to influence the domestic area in farms, and being raised on a farm might have a protective effect regarding sensitisation and allergic diseases.	125	109	2002	18		Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Home intervention in the treatment of asthma among inner-city children. Background: In Atlanta, as in other major urban areas of the United States, asthma is a leading cause of school absenteeism, emergency department use, and hospitalization. Recent guidelines for asthma management recommend reducing exposure to relevant allergens, but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty. Objective: We sought to investigate allergen avoidance as a treatment for asthma among inner-city children. Methods: One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested. The children were randomized to an active avoidance group, a placebo avoidance group, and a second control group for which no house visits occurred until the end of the first year. Avoidance included bed and pillow covers, hot washing of bedding, and cockroach bait. Eighty-five children completed the study, and the outcome was measured as unscheduled clinic visits, emergency department visits, and hospitalization for asthma, as well as changes in mite and cockroach allergen levels. Results: There was a significant decrease in acute visits for asthma among children whose homes were visited (P <.001). However, there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations. When the children with mite allergy were considered separately, there was a significant correlation between decreased mite allergen and change in acute visits (P <.01). The avoidance measures for cockroach allergen appeared to be ineffective, and the changes observed did not correlate with changes in visits. Conclusions: Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocols in this environment. The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty. Furthermore, the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population.. asthma| allergen avoidance| dust mite| children| inner city|house-dust mite| cockroach allergen| bronchial hyperreactivity| risk-factors| p-i| exposure| avoidance| sensitization| environment| antibodies.	NOV-2001	asthma| allergen avoidance| dust mite| children| inner city|house-dust mite| cockroach allergen| bronchial hyperreactivity| risk-factors| p-i| exposure| avoidance| sensitization| environment| antibodies	Carter, MC; Perzanowski, MS; Raymond, A; Platts-Mills, TAE	Home intervention in the treatment of asthma among inner-city children		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; allergen avoidance; dust mite; children; inner city	HOUSE-DUST MITE; COCKROACH ALLERGEN; BRONCHIAL HYPERREACTIVITY; RISK-FACTORS; P-I; EXPOSURE; AVOIDANCE; SENSITIZATION; ENVIRONMENT; ANTIBODIES	Background: In Atlanta, as in other major urban areas of the United States, asthma is a leading cause of school absenteeism, emergency department use, and hospitalization. Recent guidelines for asthma management recommend reducing exposure to relevant allergens, but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty. Objective: We sought to investigate allergen avoidance as a treatment for asthma among inner-city children. Methods: One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested. The children were randomized to an active avoidance group, a placebo avoidance group, and a second control group for which no house visits occurred until the end of the first year. Avoidance included bed and pillow covers, hot washing of bedding, and cockroach bait. Eighty-five children completed the study, and the outcome was measured as unscheduled clinic visits, emergency department visits, and hospitalization for asthma, as well as changes in mite and cockroach allergen levels. Results: There was a significant decrease in acute visits for asthma among children whose homes were visited (P <.001). However, there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations. When the children with mite allergy were considered separately, there was a significant correlation between decreased mite allergen and change in acute visits (P <.01). The avoidance measures for cockroach allergen appeared to be ineffective, and the changes observed did not correlate with changes in visits. Conclusions: Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocols in this environment. The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty. Furthermore, the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population.	37	109	2001	6	10.1067/mai.2001.119155	Allergy; Immunology
Predictors of airborne endotoxin in the home. We identified home characteristics associated with the level of airborne endotoxin in 111 Boston-area homes enrolled in a cohort study of home exposures and childhood asthma, and we developed a predictive model to estimate airborne endotoxin. We measured endotoxin in family-room air and in dust from the baby's bed, family room, bedroom, and kitchen floor. Level of airborne endotoxin was weakly correlated (r < 0.3) with level of endotoxin in each of the four types of dust samples and was significantly correlated with endotoxin in family-room dust (p < 0.05). Endotoxin in family-room dust accounted for < 6% of the variability of airborne endotoxin. In a multivariate model, certain home characteristics were positively (p < 0.05) associated with airborne endotoxin. These included current presence of dog (difference in level, dog vs. no dog = 72%, partial R-2 = 12.8%), past presence of dog (partial R-2 = 5.5%), and endotoxin level in family-room dust (partial R-2 = 5.3%). Use of a dehumidifier (partial R-2 = 6.4%) was negatively associated (p = 0.02; difference = -31%) with airborne endotoxin. Other home characteristics were identified as important determinants of increased airborne endotoxin in this model, but individual coefficients were not statistically significant (alpha = 0.05): total amount of fine dust collected in the home (partial R-2 = 3.8%), concrete floor in family room (3.7%), water damage (3.6%), and use of cool-mist humidifier in past year (2.7%). This multivariate model explained 42% of the variability of airborne endotoxin levels, a substantial improvement over that with dust endotoxin alone. Airborne endotoxin in Boston-area homes appears to be determined by the presence of dogs, moisture sources, and increased a-mounts of settled dust.. airborne endotoxin| dust endotoxin| predictive model| seasonal variability|lung-function| house-dust| respiratory symptoms| limulus assay| cotton dust| exposure| children| asthma| farmers| severity.	AUG-2001	airborne endotoxin| dust endotoxin| predictive model| seasonal variability|lung-function| house-dust| respiratory symptoms| limulus assay| cotton dust| exposure| children| asthma| farmers| severity	Park, JH; Spiegelman, DL; Gold, DR; Burge, HA; Milton, DK	Predictors of airborne endotoxin in the home		ENVIRONMENTAL HEALTH PERSPECTIVES	airborne endotoxin; dust endotoxin; predictive model; seasonal variability	LUNG-FUNCTION; HOUSE-DUST; RESPIRATORY SYMPTOMS; LIMULUS ASSAY; COTTON DUST; EXPOSURE; CHILDREN; ASTHMA; FARMERS; SEVERITY	We identified home characteristics associated with the level of airborne endotoxin in 111 Boston-area homes enrolled in a cohort study of home exposures and childhood asthma, and we developed a predictive model to estimate airborne endotoxin. We measured endotoxin in family-room air and in dust from the baby's bed, family room, bedroom, and kitchen floor. Level of airborne endotoxin was weakly correlated (r < 0.3) with level of endotoxin in each of the four types of dust samples and was significantly correlated with endotoxin in family-room dust (p < 0.05). Endotoxin in family-room dust accounted for < 6% of the variability of airborne endotoxin. In a multivariate model, certain home characteristics were positively (p < 0.05) associated with airborne endotoxin. These included current presence of dog (difference in level, dog vs. no dog = 72%, partial R-2 = 12.8%), past presence of dog (partial R-2 = 5.5%), and endotoxin level in family-room dust (partial R-2 = 5.3%). Use of a dehumidifier (partial R-2 = 6.4%) was negatively associated (p = 0.02; difference = -31%) with airborne endotoxin. Other home characteristics were identified as important determinants of increased airborne endotoxin in this model, but individual coefficients were not statistically significant (alpha = 0.05): total amount of fine dust collected in the home (partial R-2 = 3.8%), concrete floor in family room (3.7%), water damage (3.6%), and use of cool-mist humidifier in past year (2.7%). This multivariate model explained 42% of the variability of airborne endotoxin levels, a substantial improvement over that with dust endotoxin alone. Airborne endotoxin in Boston-area homes appears to be determined by the presence of dogs, moisture sources, and increased a-mounts of settled dust.	38	109	2001	6	10.2307/3454831	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Toll/IL-1 Signaling Is Critical for House Dust Mite-specific Th1 and Th2 Responses. Rationale: One of the immunopathological features of allergic inflammation is the infiltrationof helper T type 2 (Th2) cells to the site of disease. Activation of innate pattern recognition receptors such as Toll-like receptors (TLRs) plays a critical role in helper T type I cell differentiation, yet their contribution to the generation of Th2 responses to clinically relevant aeroallergens remains poorly defined. Objectives: To determine the requirement for TLR2, TLR4, and the Toll/IL-1 receptor domain adaptor protein MyD88 in a murine model of allergic asthma. Methods: Wild-type and factor-deficient ((-/-)) mice were sensitized intranasally to the common allergen house dust mite (HDM) and challenged 2 weeks later on four consecutive days. Measurements of allergic airway inflammation, T-cell cytokine production, and airway hyperreactivity, were performed 24 hours later. Measurements and Main Results: Mice deficient in MyD88 were protected from the cardinal features of allergic asthma, including granulocytic inflammation, Th2 cytokine production and airway hyperreactivity. Although HDM activated NF-kappa B in TLR2- or TLR4-expressing HEK cells, only in TLR4(-/-) mice was the magnitude of allergic airway inflammation and hyperreactivity attenuated. The diminished Th2 response present in MyD88(-/-) and TLR4(-/-) mice was associated with fewer OX40 ligand-expressing myeloid dendritic cells in the draining lymph nodes during allergic sensitization. Finally, HDM-specific IL-17 production and airway neutrophilia were attenuated in MyD88(-/-) but not TLR4(-/-) mice. Conclusions: Together, these data suggest that Th2- and Th17-mediated inflammation generated on inhalational HDM exposure is differentially regulated by the presence of microbial products and the activation of distinct MyD88-dependent pattern recognition receptors.. asthma| innate immunity| eosinophil| neutrophil|allergic airway inflammation| activated protein-kinase| antigen-presenting cells| toll-like receptors| dendritic cells| immune-responses| asthmatic-patients| inhaled antigen| cutting edge| ox40 ligand.	MAY 15-2009	asthma| innate immunity| eosinophil| neutrophil|allergic airway inflammation| activated protein-kinase| antigen-presenting cells| toll-like receptors| dendritic cells| immune-responses| asthmatic-patients| inhaled antigen| cutting edge| ox40 ligand	Phipps, S; Lam, CE; Kaiko, GE; Foo, SY; Collison, A; Mattes, J; Barry, J; Davidson, S; Oreo, K; Smith, L; Mansell, A; Matthaei, KI; Foster, PS	Toll/IL-1 Signaling Is Critical for House Dust Mite-specific Th1 and Th2 Responses		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; innate immunity; eosinophil; neutrophil	ALLERGIC AIRWAY INFLAMMATION; ACTIVATED PROTEIN-KINASE; ANTIGEN-PRESENTING CELLS; TOLL-LIKE RECEPTORS; DENDRITIC CELLS; IMMUNE-RESPONSES; ASTHMATIC-PATIENTS; INHALED ANTIGEN; CUTTING EDGE; OX40 LIGAND	Rationale: One of the immunopathological features of allergic inflammation is the infiltrationof helper T type 2 (Th2) cells to the site of disease. Activation of innate pattern recognition receptors such as Toll-like receptors (TLRs) plays a critical role in helper T type I cell differentiation, yet their contribution to the generation of Th2 responses to clinically relevant aeroallergens remains poorly defined. Objectives: To determine the requirement for TLR2, TLR4, and the Toll/IL-1 receptor domain adaptor protein MyD88 in a murine model of allergic asthma. Methods: Wild-type and factor-deficient ((-/-)) mice were sensitized intranasally to the common allergen house dust mite (HDM) and challenged 2 weeks later on four consecutive days. Measurements of allergic airway inflammation, T-cell cytokine production, and airway hyperreactivity, were performed 24 hours later. Measurements and Main Results: Mice deficient in MyD88 were protected from the cardinal features of allergic asthma, including granulocytic inflammation, Th2 cytokine production and airway hyperreactivity. Although HDM activated NF-kappa B in TLR2- or TLR4-expressing HEK cells, only in TLR4(-/-) mice was the magnitude of allergic airway inflammation and hyperreactivity attenuated. The diminished Th2 response present in MyD88(-/-) and TLR4(-/-) mice was associated with fewer OX40 ligand-expressing myeloid dendritic cells in the draining lymph nodes during allergic sensitization. Finally, HDM-specific IL-17 production and airway neutrophilia were attenuated in MyD88(-/-) but not TLR4(-/-) mice. Conclusions: Together, these data suggest that Th2- and Th17-mediated inflammation generated on inhalational HDM exposure is differentially regulated by the presence of microbial products and the activation of distinct MyD88-dependent pattern recognition receptors.	61	108	2009	11	10.1164/rccm.200806-974OC	General & Internal Medicine; Respiratory System
The filaggrin story: novel insights into skin-barrier function and disease. Recent reports have uncovered the key role of the protein filaggrin in maintaining an effective skin barrier against the external environment. Loss-of-function mutations in the profilaggrin gene (FLG) are common and are present in up to 10% of the population. These mutations are the cause of the semi-dominant skin-scaling disorder ichthyosis vulgaris and are a major risk factor for the development of atopic dermatitis. The discovery of these mutations also provides new data concerning the genetics of atopic asthma as well as intriguing insight into disease mechanisms of systemic allergies involving antigen exposure in skin with defective barrier function. Collectively, these novel findings have significant implications for the classification and future clinical management of patients with atopic and allergic diseases.. of-function mutations| epidermal differentiation complex| cause ichthyosis vulgaris| atopic-dermatitis| function variants| granular layer| gene| predispose| expression| psoriasis.	JAN-2008	of-function mutations| epidermal differentiation complex| cause ichthyosis vulgaris| atopic-dermatitis| function variants| granular layer| gene| predispose| expression| psoriasis	McGrath, JA; Uitto, J	The filaggrin story: novel insights into skin-barrier function and disease		TRENDS IN MOLECULAR MEDICINE		OF-FUNCTION MUTATIONS; EPIDERMAL DIFFERENTIATION COMPLEX; CAUSE ICHTHYOSIS VULGARIS; ATOPIC-DERMATITIS; FUNCTION VARIANTS; GRANULAR LAYER; GENE; PREDISPOSE; EXPRESSION; PSORIASIS	Recent reports have uncovered the key role of the protein filaggrin in maintaining an effective skin barrier against the external environment. Loss-of-function mutations in the profilaggrin gene (FLG) are common and are present in up to 10% of the population. These mutations are the cause of the semi-dominant skin-scaling disorder ichthyosis vulgaris and are a major risk factor for the development of atopic dermatitis. The discovery of these mutations also provides new data concerning the genetics of atopic asthma as well as intriguing insight into disease mechanisms of systemic allergies involving antigen exposure in skin with defective barrier function. Collectively, these novel findings have significant implications for the classification and future clinical management of patients with atopic and allergic diseases.	49	108	2008	8	10.1016/j.molmed.2007.10.006	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources. OBJECTIVES: Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources. DESIGN: In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2-17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children's total and allergen-specific serum immunoglobulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year. RESULTS: Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0.003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11). CONCLUSION: Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem.. asthma| children| damp housing| home remediation| indoor mold|inner-city asthma| respiratory health survey| environmental intervention| cockroach allergen| symptoms| exposure| dampness| sensitization| molds| dust.	OCT-2006	asthma| children| damp housing| home remediation| indoor mold|inner-city asthma| respiratory health survey| environmental intervention| cockroach allergen| symptoms| exposure| dampness| sensitization| molds| dust	Kercsmar, CM; Dearborn, DG; Schluchter, M; Xue, L; Kirchner, HL; Sobolewski, J; Greenberg, SJ; Vesper, SJ; Allan, T	Reduction in asthma morbidity in children as a result of home remediation aimed at moisture sources		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; children; damp housing; home remediation; indoor mold	INNER-CITY ASTHMA; RESPIRATORY HEALTH SURVEY; ENVIRONMENTAL INTERVENTION; COCKROACH ALLERGEN; SYMPTOMS; EXPOSURE; DAMPNESS; SENSITIZATION; MOLDS; DUST	OBJECTIVES: Home dampness and the presence of mold and allergens have been associated with asthma morbidity. We examined changes in asthma morbidity in children as a result of home remediation aimed at moisture sources. DESIGN: In this prospective, randomized controlled trial, symptomatic, asthmatic children (n = 62), 2-17 years of age, living in a home with indoor mold, received an asthma intervention including an action plan, education, and individualized problem solving. The remediation group also received household repairs, including reduction of water infiltration, removal of water-damaged building materials, and heating/ventilation/air-conditioning alterations. The control group received only home cleaning information. We measured children's total and allergen-specific serum immunoglobulin E, peripheral blood eosinophil counts, and urinary cotinine. Environmental dust samples were analyzed for dust mite, cockroach, rodent urinary protein, endotoxin, and fungi. The follow-up period was 1 year. RESULTS: Children in both groups showed improvement in asthma symptomatic days during the preremediation portion of the study. The remediation group had a significant decrease in symptom days (p = 0.003, as randomized; p = 0.004, intent to treat) after remodeling, whereas these parameters in the control group did not significantly change. In the postremediation period, the remediation group had a lower rate of exacerbations compared with control asthmatics (as treated: 1 of 29 vs. 11 of 33, respectively, p = 0.003; intent to treat: 28.1% and 10.0%, respectively, p = 0.11). CONCLUSION: Construction remediation aimed at the root cause of moisture sources and combined with a medical/behavioral intervention significantly reduces symptom days and health care use for asthmatic children who live in homes with a documented mold problem.	28	108	2006	7	10.1289/ehp.8742	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Exposure to Alternaria alternata in US homes is associated with asthma symptoms. Background: Exposure to the fungus Alternaria alternata is a risk factor for asthma. Few studies have examined Alternaria exposures in indoor environments. Objective: We examined whether exposure to A alternata in US homes was associated with asthma-related outcomes. Methods: The data for this study were collected as part of the National Survey of Lead and Allergens in Housing. This cross-sectional study surveyed a nationally representative sample of 831 housing units inhabited by 2456 individuals in 75 different locations throughout the United States. An interviewer-administered questionnaire obtained information on demographics, household characteristics, and occupants' health status. Exposure to A alternata was assessed by measuring concentrations of A alternata antigens in vacuumed dust samples using a polyclonal anti-A alternata antibody assay. Dust samples were collected from a bed, a sofa, or a chair, and from bedroom, living room, and kitchen floors. Results: Lifetime prevalence of doctor-diagnosed asthma was 11.2%, and 6.9% of the study subjects reported active asthma symptoms in the past 12 months. The prevalence of current symptomatic asthma increased with increasing Alternaria concentrations in US homes; higher levels of A alternata antigens increased the odds of having asthma symptoms in the past year (relative to the lowest tertile, adjusted odds ratio was 1.52, 95% CI, 0.90-2.55 for the 2nd tertile; and 1.84, 95% Cl, 1.18-2.85 for the 3rd tertile). Conclusion: Exposure to A alternata in US homes is associated with active asthma symptoms. Clinical implications: Measures that reduce indoor exposure to A alternata may help control asthma exacerbations.. alternaria alternata| fungal allergen| antigen| indoor| exposure| asthma| allergy|nutrition examination survey| fungal allergens| indoor allergens| national-health| airborne fungi| risk-factor| children| outdoor| spores| rhinitis.	OCT-2006	alternaria alternata| fungal allergen| antigen| indoor| exposure| asthma| allergy|nutrition examination survey| fungal allergens| indoor allergens| national-health| airborne fungi| risk-factor| children| outdoor| spores| rhinitis	Salo, PM; Arbes, SJ; Sever, M; Jaramillo, R; Cohn, RD; London, SJ; Zeldin, DC	Exposure to Alternaria alternata in US homes is associated with asthma symptoms		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	alternaria alternata; fungal allergen; antigen; indoor; exposure; asthma; allergy	NUTRITION EXAMINATION SURVEY; FUNGAL ALLERGENS; INDOOR ALLERGENS; NATIONAL-HEALTH; AIRBORNE FUNGI; RISK-FACTOR; CHILDREN; OUTDOOR; SPORES; RHINITIS	Background: Exposure to the fungus Alternaria alternata is a risk factor for asthma. Few studies have examined Alternaria exposures in indoor environments. Objective: We examined whether exposure to A alternata in US homes was associated with asthma-related outcomes. Methods: The data for this study were collected as part of the National Survey of Lead and Allergens in Housing. This cross-sectional study surveyed a nationally representative sample of 831 housing units inhabited by 2456 individuals in 75 different locations throughout the United States. An interviewer-administered questionnaire obtained information on demographics, household characteristics, and occupants' health status. Exposure to A alternata was assessed by measuring concentrations of A alternata antigens in vacuumed dust samples using a polyclonal anti-A alternata antibody assay. Dust samples were collected from a bed, a sofa, or a chair, and from bedroom, living room, and kitchen floors. Results: Lifetime prevalence of doctor-diagnosed asthma was 11.2%, and 6.9% of the study subjects reported active asthma symptoms in the past 12 months. The prevalence of current symptomatic asthma increased with increasing Alternaria concentrations in US homes; higher levels of A alternata antigens increased the odds of having asthma symptoms in the past year (relative to the lowest tertile, adjusted odds ratio was 1.52, 95% CI, 0.90-2.55 for the 2nd tertile; and 1.84, 95% Cl, 1.18-2.85 for the 3rd tertile). Conclusion: Exposure to A alternata in US homes is associated with active asthma symptoms. Clinical implications: Measures that reduce indoor exposure to A alternata may help control asthma exacerbations.	47	108	2006	7	10.1016/j.jaci.2006.07.037	Allergy; Immunology
Influence of thermal processing on the allergenicity of peanut proteins. Peanuts are one of the most common and severe food allergens. Nevertheless, the occurrence of peanut allergy varies between countries and depends on both the exposure and the way peanuts are consumed. Processing is known to influence the allergenicity of peanut proteins. The aim of this study was to assess the effect of thermal processing on the IgE-binding capacity of whole peanut protein extracts and of the major peanut allergens Ara h 1 and Ara h 2. Whole proteins, Ara h 1, and Ara h 2 were extracted and purified from raw, roasted and boiled peanuts using selective precipitation and multiple chromatographic steps, and were then characterized by electrophoresis and mass spectrometry. The immunoreactivity of whole peanut extracts and purified proteins was analyzed by the enzyme allergosorbent test (EAST) and EAST inhibition using the sera of 37 peanut-allergic patients. The composition of the whole protein extracts was modified after heat processing, especially after boiling. The electrophoretic pattern showed protein bands of low molecular weight that were less marked in boiled than in raw and roasted peanuts. The same low-molecular-weight proteins were found in the cooking water of peanuts. Whole peanut protein extracts obtained after the different processes were all recognized by the IgE of the 37 patients. The IgE-binding capacity of the whole peanut protein extracts prepared from boiled peanuts was 2-fold lower than that of the extracts prepared from raw and roasted peanuts. No significant difference was observed between protein extracts from raw and roasted peanuts. It is noteworthy that the proteins present in the cooking water were also recognized by the IgE of peanut-allergic patients. IgE immunoreactivity of purified Ara h 1 and Ara h 2 prepared from roasted peanuts was higher than that of their counterparts prepared from raw and boiled peanuts. The IgE-binding capacity of purified Ara h 1 and Ara h 2 was altered by heat treatment and in particular was increased by roasting. However, no significant difference in IgE immunoreactivity was observed between whole protein extracts from raw and roasted peanuts. The decrease in allergenicity of boiled peanuts results mainly from a transfer of low-molecular-weight allergens into the water during cooking.. thermal processing| peanut allergens| allergenicity|controlled food challenge| atopic-dermatitis| double-blind| ige-binding| allergy| identification| cooking| update.	JUN 1-2005	thermal processing| peanut allergens| allergenicity|controlled food challenge| atopic-dermatitis| double-blind| ige-binding| allergy| identification| cooking| update	Mondoulet, L; Paty, E; Drumare, MF; Ah-Leung, S; Scheinmann, P; Willemot, RM; Wal, JM; Bernard, H	Influence of thermal processing on the allergenicity of peanut proteins		JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY	thermal processing; peanut allergens; allergenicity	CONTROLLED FOOD CHALLENGE; ATOPIC-DERMATITIS; DOUBLE-BLIND; IGE-BINDING; ALLERGY; IDENTIFICATION; COOKING; UPDATE	Peanuts are one of the most common and severe food allergens. Nevertheless, the occurrence of peanut allergy varies between countries and depends on both the exposure and the way peanuts are consumed. Processing is known to influence the allergenicity of peanut proteins. The aim of this study was to assess the effect of thermal processing on the IgE-binding capacity of whole peanut protein extracts and of the major peanut allergens Ara h 1 and Ara h 2. Whole proteins, Ara h 1, and Ara h 2 were extracted and purified from raw, roasted and boiled peanuts using selective precipitation and multiple chromatographic steps, and were then characterized by electrophoresis and mass spectrometry. The immunoreactivity of whole peanut extracts and purified proteins was analyzed by the enzyme allergosorbent test (EAST) and EAST inhibition using the sera of 37 peanut-allergic patients. The composition of the whole protein extracts was modified after heat processing, especially after boiling. The electrophoretic pattern showed protein bands of low molecular weight that were less marked in boiled than in raw and roasted peanuts. The same low-molecular-weight proteins were found in the cooking water of peanuts. Whole peanut protein extracts obtained after the different processes were all recognized by the IgE of the 37 patients. The IgE-binding capacity of the whole peanut protein extracts prepared from boiled peanuts was 2-fold lower than that of the extracts prepared from raw and roasted peanuts. No significant difference was observed between protein extracts from raw and roasted peanuts. It is noteworthy that the proteins present in the cooking water were also recognized by the IgE of peanut-allergic patients. IgE immunoreactivity of purified Ara h 1 and Ara h 2 prepared from roasted peanuts was higher than that of their counterparts prepared from raw and boiled peanuts. The IgE-binding capacity of purified Ara h 1 and Ara h 2 was altered by heat treatment and in particular was increased by roasting. However, no significant difference in IgE immunoreactivity was observed between whole protein extracts from raw and roasted peanuts. The decrease in allergenicity of boiled peanuts results mainly from a transfer of low-molecular-weight allergens into the water during cooking.	27	108	2005	7	10.1021/jf050091p	Agriculture; Chemistry; Food Science & Technology
The introduction of solids in relation to asthma and eczema. Background: Despite scarce scientific evidence, current feeding guidelines recommend delayed introduction of solids for the prevention of asthma and allergy. Aims: To explore whether late introduction of solids is protective against the development of asthma, eczema, and atopy. Methods: A total of 642 children were recruited before birth and followed to the age of 5 1/2 years. Main outcome measures were: doctor's diagnosis of eczema ever, atopy according to skin prick test results against inhalant allergens, preschool wheezing, transient wheezing, all defined at age 5 - 5 1/2 years. Introduction of solids as main exposure measure was assessed retrospectively at age 1 year. Results: There was no evidence for a protective effect of late introduction of solids for the development of preschool wheezing, transient wheezing, atopy, or eczema. On the contrary, there was a statistically significant increased risk of eczema in relation to late introduction of egg (aOR 1.6, 95% CI 1.1 to 2.4) and milk (aOR 1.7, 95% CI 1.1 to 2.5). Late introduction of egg was furthermore associated with a nonsignificant increased risk of preschool wheezing (aOR 1.5, 95% CI 0.92 to 2.4). There was no statistical evidence of feeding practices playing a different role in the development of asthma and eczema after stratification for parental asthma and atopy status. Conclusions: Results do not support the recommendations given by present feeding guidelines stating that a delayed introduction of solids is protective against the development of asthma and allergy.. follow-up| infant diet| children| atopy| life| sensitization| cohort| risk| food| age.	APR 1-2004	follow-up| infant diet| children| atopy| life| sensitization| cohort| risk| food| age	Zutavern, A; von Mutius, E; Harris, J; Mills, P; Moffatt, S; White, C; Cullinan, P	The introduction of solids in relation to asthma and eczema		ARCHIVES OF DISEASE IN CHILDHOOD		FOLLOW-UP; INFANT DIET; CHILDREN; ATOPY; LIFE; SENSITIZATION; COHORT; RISK; FOOD; AGE	Background: Despite scarce scientific evidence, current feeding guidelines recommend delayed introduction of solids for the prevention of asthma and allergy. Aims: To explore whether late introduction of solids is protective against the development of asthma, eczema, and atopy. Methods: A total of 642 children were recruited before birth and followed to the age of 5 1/2 years. Main outcome measures were: doctor's diagnosis of eczema ever, atopy according to skin prick test results against inhalant allergens, preschool wheezing, transient wheezing, all defined at age 5 - 5 1/2 years. Introduction of solids as main exposure measure was assessed retrospectively at age 1 year. Results: There was no evidence for a protective effect of late introduction of solids for the development of preschool wheezing, transient wheezing, atopy, or eczema. On the contrary, there was a statistically significant increased risk of eczema in relation to late introduction of egg (aOR 1.6, 95% CI 1.1 to 2.4) and milk (aOR 1.7, 95% CI 1.1 to 2.5). Late introduction of egg was furthermore associated with a nonsignificant increased risk of preschool wheezing (aOR 1.5, 95% CI 0.92 to 2.4). There was no statistical evidence of feeding practices playing a different role in the development of asthma and eczema after stratification for parental asthma and atopy status. Conclusions: Results do not support the recommendations given by present feeding guidelines stating that a delayed introduction of solids is protective against the development of asthma and allergy.	19	108	2004	6	10.1136/adc.2002.025353	Pediatrics
Release of allergens as respirable aerosols: A link between grass pollen and asthma. Background: Asthma incidence has long been linked to pollen, even though pollen grains are too large to penetrate into the airways where asthmatic responses originate. Pollen allergens found in small, respirable particles have been implicated in a number of asthma epidemics, particularly ones following rainfall or thunderstorms. Objective: The aim of this study was to determine how pollen allergens form the respirable aerosols necessary for triggering asthma. Methods: Flowering grasses were humidified and then dried in a controlled-environment chamber connected to a cascade impactor and an aerosol particle counter. Particles shed from the flowers were analyzed with high-resolution microscopy and immunolabeled with rabbit anti-Phl p 1 antibody, which is specific for group 1 pollen allergens. Results: Contrary to what has been reported in other published accounts, most of the pollen in this investigation remained on the open anthers of wind pollinated plants unless disturbed-eg, by wind. Increasing humidity caused anthers to close. After a cycle of wetting and drying followed by wind disturbance, grasses flowering within a chamber produced an aerosol of particles that were collected in a cascade impactor. These particles consisted of fragmented pollen cytoplasm in the size range 0.12 to 4.67 mum; they were loaded with group I allergens. Conclusion: Here we provide the first direct observations of the release of grass pollen allergens as respirable aerosols. They can emanate directly from the flower after a moisture-drying cycle. This could explain asthmatic responses associated with grass pollination, particularly after moist weather conditions.. grass| pollen| allergen| aerosol| asthma| air pollution|rye-grass| environmental-factors| diesel exhaust| air-pollution| city| particles| melbourne| weather| risk.	JAN-2002	grass| pollen| allergen| aerosol| asthma| air pollution|rye-grass| environmental-factors| diesel exhaust| air-pollution| city| particles| melbourne| weather| risk	Taylor, PE; Flagan, RC; Valenta, R; Glovsky, MM	Release of allergens as respirable aerosols: A link between grass pollen and asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	grass; pollen; allergen; aerosol; asthma; air pollution	RYE-GRASS; ENVIRONMENTAL-FACTORS; DIESEL EXHAUST; AIR-POLLUTION; CITY; PARTICLES; MELBOURNE; WEATHER; RISK	Background: Asthma incidence has long been linked to pollen, even though pollen grains are too large to penetrate into the airways where asthmatic responses originate. Pollen allergens found in small, respirable particles have been implicated in a number of asthma epidemics, particularly ones following rainfall or thunderstorms. Objective: The aim of this study was to determine how pollen allergens form the respirable aerosols necessary for triggering asthma. Methods: Flowering grasses were humidified and then dried in a controlled-environment chamber connected to a cascade impactor and an aerosol particle counter. Particles shed from the flowers were analyzed with high-resolution microscopy and immunolabeled with rabbit anti-Phl p 1 antibody, which is specific for group 1 pollen allergens. Results: Contrary to what has been reported in other published accounts, most of the pollen in this investigation remained on the open anthers of wind pollinated plants unless disturbed-eg, by wind. Increasing humidity caused anthers to close. After a cycle of wetting and drying followed by wind disturbance, grasses flowering within a chamber produced an aerosol of particles that were collected in a cascade impactor. These particles consisted of fragmented pollen cytoplasm in the size range 0.12 to 4.67 mum; they were loaded with group I allergens. Conclusion: Here we provide the first direct observations of the release of grass pollen allergens as respirable aerosols. They can emanate directly from the flower after a moisture-drying cycle. This could explain asthmatic responses associated with grass pollination, particularly after moist weather conditions.	38	108	2002	6	10.1067/mai.2002.120759	Allergy; Immunology
Quantitative IgE antibody assays in allergic diseases. During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously. Elevated egg-specific IgE antibody levels in infancy are associated with significantly increased risk for development of inhalant allergies later in childhood. In cases of inhalant allergy, specific IgE antibody levels correlate closely with results of inhalation challenge studies in cat-sensitive persons. Also, mite-specific IgE antibody levels correlate significantly with the mite allergen contents of reservoir dust in the homes of mite-sensitive persons. Immunoassays for quantitation of specific IgE antibodies may be used to document allergen sensitization over time and to evaluate the risk of reaction on allergen exposure. However, immunoassays and skin tests are not entirely interchangeable, and neither will replace the other in appropriate circumstances.. ige antibody| quantitative immunoassay| allergic disease|skin-test reactivity| high-risk children| atopic-dermatitis| performance-characteristics| food allergens| egg allergy| follow-up| sensitization| diagnosis| asthma.	JUN-2000	ige antibody| quantitative immunoassay| allergic disease|skin-test reactivity| high-risk children| atopic-dermatitis| performance-characteristics| food allergens| egg allergy| follow-up| sensitization| diagnosis| asthma	Yunginger, JW; Ahlstedt, S; Eggleston, PA; Homburger, HA; Nelson, HS; Ownby, DR; Platts-Mills, TAE; Sampson, HA; Sicherer, SH; Weinstein, AM; Williams, PB; Wood, RA; Zeiger, RS	Quantitative IgE antibody assays in allergic diseases		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	IgE antibody; quantitative immunoassay; allergic disease	SKIN-TEST REACTIVITY; HIGH-RISK CHILDREN; ATOPIC-DERMATITIS; PERFORMANCE-CHARACTERISTICS; FOOD ALLERGENS; EGG ALLERGY; FOLLOW-UP; SENSITIZATION; DIAGNOSIS; ASTHMA	During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously. Elevated egg-specific IgE antibody levels in infancy are associated with significantly increased risk for development of inhalant allergies later in childhood. In cases of inhalant allergy, specific IgE antibody levels correlate closely with results of inhalation challenge studies in cat-sensitive persons. Also, mite-specific IgE antibody levels correlate significantly with the mite allergen contents of reservoir dust in the homes of mite-sensitive persons. Immunoassays for quantitation of specific IgE antibodies may be used to document allergen sensitization over time and to evaluate the risk of reaction on allergen exposure. However, immunoassays and skin tests are not entirely interchangeable, and neither will replace the other in appropriate circumstances.	49	108	2000	8	10.1067/mai.2000.107041	Allergy; Immunology
Safety of sublingual-swallow immunotherapy in children and adults. Background: Immunotherapy is an established treatment of allergic diseases. The safety of this treatment, particularly when administered without direct medical surveillance, as in the case of the sublingual-swallow route needs to be established. The aim of this paper is to review the safety of the sublingual-swallow immunotherapy as reported in eight double-blind, placebo-controlled trials carried out in France, Italy and Greece. Methods: Six hundred and ninety subjects, 472 adults and 218 children, took part in trials of specific immunotherapy (SIT) for the treatment of rhinoconjunctivitis and/or asthma. Three hundred and forty-seven patients received SIT and 343 patients received placebo. Treatment with specific immunotherapy with allergen extracts or placebo was administered using the sublingual-swallow technique. The allergens administered were grass, ambrosia, parietaria and olive pollens, and mites. The daily dose taken during maintenance therapy ranged from 100 to 300 IR (index of reactivity) and cumulative doses ranged from 4,500 to 104,000 IR. Treatment duration ranged from 4 months to 2 years. Adverse events reported either spontaneously by the patient or on direct questioning by the investigator were analysed. Results: One hundred and forty-five unusual events were reported in the subjects receiving active SIT and 79 in those receiving placebo (p < 0.001). Of these 85 were children aged 15 years or less (50 received active SIT, 35 placebo) and 139 were adults (95 received SIT, 44 placebo). Unusual events involving the buccal cavity (61 SIT, 13 placebo) and the gastro-intestinal tract (47 SIT, 15 placebo) were significantly more frequent in the SIT-treated patients (p < 0.001). Wheezing (9 SIT, 21 placebo) was more frequent in the placebo-treated patients (p < 0.05). There were no differences in the frequency of unusual events between adults and children and in the frequency of events involving other body systems. No event was reported as serious. Two events reported as laryngeal oedema were not considered to be accurate descriptions. Conclusions: No serious adverse event was reported in the studies monitored, confirming the good safety profile of the sublingual-swallow method both in children and adults with rhinitis or moderate asthma. (C) 2000 S. Karger AG, Basel.. immunotherapy, sublingual-swallow| asthma| rhinoconjunctivitis| mites| pollen|placebo-controlled trial| double-blind placebo| house-dust mite| pollen extract| rhinitis| rhinoconjunctivitis| efficacy| asthma.	MAR-2000	immunotherapy, sublingual-swallow| asthma| rhinoconjunctivitis| mites| pollen|placebo-controlled trial| double-blind placebo| house-dust mite| pollen extract| rhinitis| rhinoconjunctivitis| efficacy| asthma	Andre, C; Vatrinet, C; Galvain, S; Carat, F; Sicard, H	Safety of sublingual-swallow immunotherapy in children and adults		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	immunotherapy, sublingual-swallow; asthma; rhinoconjunctivitis; mites; pollen	PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND PLACEBO; HOUSE-DUST MITE; POLLEN EXTRACT; RHINITIS; RHINOCONJUNCTIVITIS; EFFICACY; ASTHMA	Background: Immunotherapy is an established treatment of allergic diseases. The safety of this treatment, particularly when administered without direct medical surveillance, as in the case of the sublingual-swallow route needs to be established. The aim of this paper is to review the safety of the sublingual-swallow immunotherapy as reported in eight double-blind, placebo-controlled trials carried out in France, Italy and Greece. Methods: Six hundred and ninety subjects, 472 adults and 218 children, took part in trials of specific immunotherapy (SIT) for the treatment of rhinoconjunctivitis and/or asthma. Three hundred and forty-seven patients received SIT and 343 patients received placebo. Treatment with specific immunotherapy with allergen extracts or placebo was administered using the sublingual-swallow technique. The allergens administered were grass, ambrosia, parietaria and olive pollens, and mites. The daily dose taken during maintenance therapy ranged from 100 to 300 IR (index of reactivity) and cumulative doses ranged from 4,500 to 104,000 IR. Treatment duration ranged from 4 months to 2 years. Adverse events reported either spontaneously by the patient or on direct questioning by the investigator were analysed. Results: One hundred and forty-five unusual events were reported in the subjects receiving active SIT and 79 in those receiving placebo (p < 0.001). Of these 85 were children aged 15 years or less (50 received active SIT, 35 placebo) and 139 were adults (95 received SIT, 44 placebo). Unusual events involving the buccal cavity (61 SIT, 13 placebo) and the gastro-intestinal tract (47 SIT, 15 placebo) were significantly more frequent in the SIT-treated patients (p < 0.001). Wheezing (9 SIT, 21 placebo) was more frequent in the placebo-treated patients (p < 0.05). There were no differences in the frequency of unusual events between adults and children and in the frequency of events involving other body systems. No event was reported as serious. Two events reported as laryngeal oedema were not considered to be accurate descriptions. Conclusions: No serious adverse event was reported in the studies monitored, confirming the good safety profile of the sublingual-swallow method both in children and adults with rhinitis or moderate asthma. (C) 2000 S. Karger AG, Basel.	23	108	2000	6	10.1159/000024322	Allergy; Immunology
"Atopic dermatitis: A practice parameter update 2012. This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing ""Atopic dermatitis: a practice parameter update 2012.'' This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. Published practice parameters of the Joint Task Force on Practice Parameters for Allergy & Immunology are available online at http://www.jcaai.org. (J Allergy Clin Immunol 2013;131:295-9.). atopic dermatitis/atopic eczema| pathogenesis| genetics| diagnosis| management| therapy| triggers| staphylococcus| quality of life| sleep| cyclosporine| immunomodulating agents| phototherapy| allergen immunotherapy|pimecrolimus cream 1-percent| randomized controlled-trial| long-term treatment| quality-of-life| staphylococcus-aureus colonization| placebo-controlled trial| oral food challenges| wet-wrap dressings| house-dust mite| thiopurine methyltransferase activity."	FEB-2013	atopic dermatitis/atopic eczema| pathogenesis| genetics| diagnosis| management| therapy| triggers| staphylococcus| quality of life| sleep| cyclosporine| immunomodulating agents| phototherapy| allergen immunotherapy|pimecrolimus cream 1-percent| randomized controlled-trial| long-term treatment| quality-of-life| staphylococcus-aureus colonization| placebo-controlled trial| oral food challenges| wet-wrap dressings| house-dust mite| thiopurine methyltransferase activity	Schneider, L; Tilles, S; Lio, P; Boguniewicz, M; Beck, L; LeBovidge, J; Novak, N	Atopic dermatitis: A practice parameter update 2012		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Atopic dermatitis/atopic eczema; pathogenesis; genetics; diagnosis; management; therapy; triggers; Staphylococcus; quality of life; sleep; cyclosporine; immunomodulating agents; phototherapy; allergen immunotherapy	PIMECROLIMUS CREAM 1-PERCENT; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM TREATMENT; QUALITY-OF-LIFE; STAPHYLOCOCCUS-AUREUS COLONIZATION; PLACEBO-CONTROLLED TRIAL; ORAL FOOD CHALLENGES; WET-WRAP DRESSINGS; HOUSE-DUST MITE; THIOPURINE METHYLTRANSFERASE ACTIVITY	"This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing ""Atopic dermatitis: a practice parameter update 2012.'' This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. Published practice parameters of the Joint Task Force on Practice Parameters for Allergy & Immunology are available online at http://www.jcaai.org. (J Allergy Clin Immunol 2013;131:295-9.)"	249	107	2013	32	10.1016/j.jaci.2012.12.672	Allergy; Immunology
Residential Proximity to Freeways and Autism in the CHARGE Study. BACKGROUND: Little is known about environmental causes and contributing factors for autism. Basic science and epidemiologic research suggest that oxidative stress and inflammation may play a role in disease development. Traffic-related air pollution, a common exposure with established effects on these pathways, contains substances found to have adverse prenatal effects. OBJECTIVES: We examined the association between autism and proximity of residence to freeways and major roadways during pregnancy and near the time of delivery, as a surrogate for air pollution exposure. METHODS: Data were from 304 autism cases and 259 typically developing controls enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. The mother's address recorded on the birth certificate and trimester-specific addresses derived from a residential history obtained by questionnaire were geocoded, and measures of distance to freeways and major roads were calculated using ArcGIS software. Logistic regression models compared residential proximity to freeways and major roads for autism cases and typically developing controls. RESULTS: Adjusting for sociodemographic factors and maternal smoking, maternal residence at the time of delivery was more likely be near a freeway (<= 309 m) for cases than for controls [odds ratio (OR) = 1.86; 95% confidence interval (CI), 1.04-3.45]. Autism was also associated with residential proximity to a freeway during the third trimester (OR = 2.22; CI, 1.16-4.42). After adjustment for socioeconomic and sociodemographic characteristics, these associations were unchanged. Living near other major roads at birth was not associated with autism. CONCLUSIONS: Living near a freeway was associated with autism. Examination of associations with measured air pollutants is needed.. autism| epidemiology| gene-environment interaction| roadway proximity| traffic emissions|polycyclic aromatic-hydrocarbons| hazardous air-pollutants| spectrum disorders| prenatal exposure| childhood asthma| oxidative stress| multiethnic population| ultrafine particles| nitrogen-dioxide| gene-expression.	JUN-2011	autism| epidemiology| gene-environment interaction| roadway proximity| traffic emissions|polycyclic aromatic-hydrocarbons| hazardous air-pollutants| spectrum disorders| prenatal exposure| childhood asthma| oxidative stress| multiethnic population| ultrafine particles| nitrogen-dioxide| gene-expression	Volk, HE; Hertz-Picciotto, I; Delwiche, L; Lurmann, F; McConnell, R	Residential Proximity to Freeways and Autism in the CHARGE Study		ENVIRONMENTAL HEALTH PERSPECTIVES	autism; epidemiology; gene-environment interaction; roadway proximity; traffic emissions	POLYCYCLIC AROMATIC-HYDROCARBONS; HAZARDOUS AIR-POLLUTANTS; SPECTRUM DISORDERS; PRENATAL EXPOSURE; CHILDHOOD ASTHMA; OXIDATIVE STRESS; MULTIETHNIC POPULATION; ULTRAFINE PARTICLES; NITROGEN-DIOXIDE; GENE-EXPRESSION	BACKGROUND: Little is known about environmental causes and contributing factors for autism. Basic science and epidemiologic research suggest that oxidative stress and inflammation may play a role in disease development. Traffic-related air pollution, a common exposure with established effects on these pathways, contains substances found to have adverse prenatal effects. OBJECTIVES: We examined the association between autism and proximity of residence to freeways and major roadways during pregnancy and near the time of delivery, as a surrogate for air pollution exposure. METHODS: Data were from 304 autism cases and 259 typically developing controls enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. The mother's address recorded on the birth certificate and trimester-specific addresses derived from a residential history obtained by questionnaire were geocoded, and measures of distance to freeways and major roads were calculated using ArcGIS software. Logistic regression models compared residential proximity to freeways and major roads for autism cases and typically developing controls. RESULTS: Adjusting for sociodemographic factors and maternal smoking, maternal residence at the time of delivery was more likely be near a freeway (<= 309 m) for cases than for controls [odds ratio (OR) = 1.86; 95% confidence interval (CI), 1.04-3.45]. Autism was also associated with residential proximity to a freeway during the third trimester (OR = 2.22; CI, 1.16-4.42). After adjustment for socioeconomic and sociodemographic characteristics, these associations were unchanged. Living near other major roads at birth was not associated with autism. CONCLUSIONS: Living near a freeway was associated with autism. Examination of associations with measured air pollutants is needed.	71	107	2011	5	10.1289/ehp.1002835	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water. BACKGROUND: Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in the water and related that to mutagenicity. OBJECTIVES: We performed a comprehensive identification of DBPs and disinfectant species in waters from public swimming pools in Barcelona, Catalonia, Spain, that disinfect with either chlorine or bromine and we determined the mutagenicity of the waters to compare with the analytical results. METHODS: We used gas chromatography/mass spectrometry (GC/MS) to measure trihalomethanes in water, GC with electron capture detection for air, low- and high-resolution GC/MS to comprehensively identify DBPs, photometry to measure disinfectant species (free chlorine, monochloroamine, dichloramine, and trichloramine) in the waters, and an ion chromatography method to measure trichloramine in air. We assessed mutagenicity with the Salmonella mutagenicity assay. RESULTS: We identified > 100 DBPs, including many nitrogen-containing DBPs that were likely formed from nitrogen-containing precursors from human inputs, such as urine, sweat, and skin cells. Many DBPs were new and have not been reported previously in either swimming pool or drinking waters. Bromoform levels were greater in brominated than in chlorinated pool waters, but we also identified many brominated DBPs in the chlorinated waters. The pool waters were mutagenic at levels similar to that of drinking water (similar to 1,200 revertants/L-equivalents in strain TA100-S9 mix). CONCLUSIONS: This study identified many new DBPs not identified previously in swimming pool or drinking water and found that swimming pool waters are as mutagenic as typical drinking waters.. bromination| bromine| chlorination| chlorine| dbps| disinfection by-products| mutagenicity| swimming pools| salmonella| water|glutathione-s-transferase| drinking-water| trihalomethane concentrations| salmonella mutagenicity| exposure| genotoxicity| bromodichloromethane| chloramines| chloroform| expression.	NOV-2010	bromination| bromine| chlorination| chlorine| dbps| disinfection by-products| mutagenicity| swimming pools| salmonella| water|glutathione-s-transferase| drinking-water| trihalomethane concentrations| salmonella mutagenicity| exposure| genotoxicity| bromodichloromethane| chloramines| chloroform| expression	Richardson, SD; DeMarini, DM; Kogevinas, M; Fernandez, P; Marco, E; Lourencetti, C; Balleste, C; Heederik, D; Meliefste, K; McKague, AB; Marcos, R; Font-Ribera, L; Grimalt, JO; Villanueva, CM	What's in the Pool? A Comprehensive Identification of Disinfection By-products and Assessment of Mutagenicity of Chlorinated and Brominated Swimming Pool Water		ENVIRONMENTAL HEALTH PERSPECTIVES	bromination; bromine; chlorination; chlorine; DBPs; disinfection by-products; mutagenicity; swimming pools; Salmonella; water	GLUTATHIONE-S-TRANSFERASE; DRINKING-WATER; TRIHALOMETHANE CONCENTRATIONS; SALMONELLA MUTAGENICITY; EXPOSURE; GENOTOXICITY; BROMODICHLOROMETHANE; CHLORAMINES; CHLOROFORM; EXPRESSION	BACKGROUND: Swimming pool disinfectants and disinfection by-products (DBPs) have been linked to human health effects, including asthma and bladder cancer, but no studies have provided a comprehensive identification of DBPs in the water and related that to mutagenicity. OBJECTIVES: We performed a comprehensive identification of DBPs and disinfectant species in waters from public swimming pools in Barcelona, Catalonia, Spain, that disinfect with either chlorine or bromine and we determined the mutagenicity of the waters to compare with the analytical results. METHODS: We used gas chromatography/mass spectrometry (GC/MS) to measure trihalomethanes in water, GC with electron capture detection for air, low- and high-resolution GC/MS to comprehensively identify DBPs, photometry to measure disinfectant species (free chlorine, monochloroamine, dichloramine, and trichloramine) in the waters, and an ion chromatography method to measure trichloramine in air. We assessed mutagenicity with the Salmonella mutagenicity assay. RESULTS: We identified > 100 DBPs, including many nitrogen-containing DBPs that were likely formed from nitrogen-containing precursors from human inputs, such as urine, sweat, and skin cells. Many DBPs were new and have not been reported previously in either swimming pool or drinking waters. Bromoform levels were greater in brominated than in chlorinated pool waters, but we also identified many brominated DBPs in the chlorinated waters. The pool waters were mutagenic at levels similar to that of drinking water (similar to 1,200 revertants/L-equivalents in strain TA100-S9 mix). CONCLUSIONS: This study identified many new DBPs not identified previously in swimming pool or drinking water and found that swimming pool waters are as mutagenic as typical drinking waters.	54	107	2010	8	10.1289/ehp.1001965	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
"Short-Term Effects of PM10 and NO2 on Respiratory Health among Children with Asthma or Asthma-like Symptoms: A Systematic Review and Meta-Analysis. OBJECTIVE: Our goal was to quantify the short-term effects of particulate matter with aerodynamic diameter <= 10 mu m (PM10) and nitrogen dioxide (NO2) on respiratory health of asthmatic children from published panel studies, and to investigate the influence of study and population characteristics as effect modifiers. DATA EXTRACTION: After a systematic literature review, we extracted quantitative estimates of the association of PM10 and/or NO2 with respiratory symptoms and peak expiratory flow (PEF). Combined effect estimates for an increase of 10 mu g/m(3) were calculated by random effects meta-analysis for all studies and for different strata defined by study characteristics. The effect of publication bias was investigated with Egger's and Begg's tests and ""trim-and-fill"" analyses. DATA SYNTHESIS: We identified 36 studies; 14 were part of the European Pollution Effects on Asthmatic Children in Europe (PEACE) study. Adverse associations of PM10 with asthma symptoms were statistically significant [odds ratio (OR) = 1.028; 95% confidence interval (CI), 1.006-1.051]. There were also associations, although not statistically significant, of PM10 with cough (OR = 1.012; 95% CI, 0.997-1.026) and on PEF (decrease of-0.082 L/min; 95% CI, -0.214 to 0.050). NO2 had statistically significant associations with asthma symptoms in the overall analysis considering all possible lags (OR = 1.031; 95% CI, 1.001-1.062), but not when we evaluated only the 0-1 lag. We found no publication bias, although it appeared when excluding the PEACE studies. When we applied the trim-and-fill method to the data set without the PEACE studies, the results were similar to the overall estimates from all studies. There was an indication for stronger PM10 associations for studies conducted in summer, outside of Europe, with longer lags, and in locations with higher NO2 concentrations. CONCLUSIONS: We found clear evidence of effects of PM10 on the occurrence of asthma symptom episodes, and to a lesser extent on cough and PEF. The results for NO2 are more difficult to interpret because they depend on the lag times examined. There was an indication of effect modification by several study conditions.. air pollution| asthma| children| no2| pm| short-term effects|particulate air-pollution| antiinflammatory medication use| peak expiratory flow| nitrogen-dioxide| australian children| publication bias| mexico-city| particles| exposure| project."	APR-2010	air pollution| asthma| children| no2| pm| short-term effects|particulate air-pollution| antiinflammatory medication use| peak expiratory flow| nitrogen-dioxide| australian children| publication bias| mexico-city| particles| exposure| project	Weinmayr, G; Romeo, E; De Sario, M; Weiland, SK; Forastiere, F	Short-Term Effects of PM10 and NO2 on Respiratory Health among Children with Asthma or Asthma-like Symptoms: A Systematic Review and Meta-Analysis		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma; children; NO2; PM; short-term effects	PARTICULATE AIR-POLLUTION; ANTIINFLAMMATORY MEDICATION USE; PEAK EXPIRATORY FLOW; NITROGEN-DIOXIDE; AUSTRALIAN CHILDREN; PUBLICATION BIAS; MEXICO-CITY; PARTICLES; EXPOSURE; PROJECT	"OBJECTIVE: Our goal was to quantify the short-term effects of particulate matter with aerodynamic diameter <= 10 mu m (PM10) and nitrogen dioxide (NO2) on respiratory health of asthmatic children from published panel studies, and to investigate the influence of study and population characteristics as effect modifiers. DATA EXTRACTION: After a systematic literature review, we extracted quantitative estimates of the association of PM10 and/or NO2 with respiratory symptoms and peak expiratory flow (PEF). Combined effect estimates for an increase of 10 mu g/m(3) were calculated by random effects meta-analysis for all studies and for different strata defined by study characteristics. The effect of publication bias was investigated with Egger's and Begg's tests and ""trim-and-fill"" analyses. DATA SYNTHESIS: We identified 36 studies; 14 were part of the European Pollution Effects on Asthmatic Children in Europe (PEACE) study. Adverse associations of PM10 with asthma symptoms were statistically significant [odds ratio (OR) = 1.028; 95% confidence interval (CI), 1.006-1.051]. There were also associations, although not statistically significant, of PM10 with cough (OR = 1.012; 95% CI, 0.997-1.026) and on PEF (decrease of-0.082 L/min; 95% CI, -0.214 to 0.050). NO2 had statistically significant associations with asthma symptoms in the overall analysis considering all possible lags (OR = 1.031; 95% CI, 1.001-1.062), but not when we evaluated only the 0-1 lag. We found no publication bias, although it appeared when excluding the PEACE studies. When we applied the trim-and-fill method to the data set without the PEACE studies, the results were similar to the overall estimates from all studies. There was an indication for stronger PM10 associations for studies conducted in summer, outside of Europe, with longer lags, and in locations with higher NO2 concentrations. CONCLUSIONS: We found clear evidence of effects of PM10 on the occurrence of asthma symptom episodes, and to a lesser extent on cough and PEF. The results for NO2 are more difficult to interpret because they depend on the lag times examined. There was an indication of effect modification by several study conditions."	66	107	2010	9	10.1289/ehp.0900844	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
The Mucosal Immune System and Its Integration with the Mammary Glands. Mucosal immunity reduces the need for elimination of penetrating exogenous antigens by proinflammatory systemic immunity. The adult gut mucosa contains some 80% of the body's activated B cells-differentiated to plasmablasts and plasma cells (PCs). Most mucosal PCs produce dimeric immunoglobulin A (IgA), which, along with pentameric immunoglobulin M (IgM), can be exported by secretory epithelia expressing the polymeric immunoglobulin receptor. Immune exclusion of antigens is performed mainly by secretory IgA in cooperation with innate defenses, but, in newborns and in IgA deficiency, secretory IgM is important. In the gut, induction and regulation of mucosal immunity occurs primarily in gut-associated lymphoid tissue-particularly the Peyer's patches-and also in mesenteric lymph nodes. Terminal differentiation to PCs is accomplished in the lamina propria to which the activated memory/effector T and B cells home. Lactating mammary glands are part of the secretory immune system, and IgA antibodies in breast milk reflect antigenic stimulation of gut-associated lymphoid tissue and nasopharynx-associated lymphoid tissue such as the tonsils. Breast-milk antibodies are thus highly targeted against infectious agents and other exogenous antigens in the mother's environment, which are those likely to be encountered by the infant. Therefore breast-feeding represents an ingenious immunologic integration of mother and child. (J Pediatr 2010;156:S8-15).. cesarean-section| epithelial-cells| dendritic cells| food allergy| b-cells| j-chain| tolerance| transport| responses| component.	FEB-2010	cesarean-section| epithelial-cells| dendritic cells| food allergy| b-cells| j-chain| tolerance| transport| responses| component	Brandtzaeg, P	The Mucosal Immune System and Its Integration with the Mammary Glands		JOURNAL OF PEDIATRICS		CESAREAN-SECTION; EPITHELIAL-CELLS; DENDRITIC CELLS; FOOD ALLERGY; B-CELLS; J-CHAIN; TOLERANCE; TRANSPORT; RESPONSES; COMPONENT	Mucosal immunity reduces the need for elimination of penetrating exogenous antigens by proinflammatory systemic immunity. The adult gut mucosa contains some 80% of the body's activated B cells-differentiated to plasmablasts and plasma cells (PCs). Most mucosal PCs produce dimeric immunoglobulin A (IgA), which, along with pentameric immunoglobulin M (IgM), can be exported by secretory epithelia expressing the polymeric immunoglobulin receptor. Immune exclusion of antigens is performed mainly by secretory IgA in cooperation with innate defenses, but, in newborns and in IgA deficiency, secretory IgM is important. In the gut, induction and regulation of mucosal immunity occurs primarily in gut-associated lymphoid tissue-particularly the Peyer's patches-and also in mesenteric lymph nodes. Terminal differentiation to PCs is accomplished in the lamina propria to which the activated memory/effector T and B cells home. Lactating mammary glands are part of the secretory immune system, and IgA antibodies in breast milk reflect antigenic stimulation of gut-associated lymphoid tissue and nasopharynx-associated lymphoid tissue such as the tonsils. Breast-milk antibodies are thus highly targeted against infectious agents and other exogenous antigens in the mother's environment, which are those likely to be encountered by the infant. Therefore breast-feeding represents an ingenious immunologic integration of mother and child. (J Pediatr 2010;156:S8-15).	32	107	2010	8	10.1016/j.jpeds.2009.11.014	Pediatrics
Gene-environment interactions in asthma. Asthma is a complex disease, and its incidence is determined by an intricate interplay of genetic and environmental factors. The Identification of novel genes for asthma suggests that many genes with small effect,; rather than few genes with strong effects contribute to the development of asthma. These genetic effects may in part differ with respect to a subject's environmental exposures, although some genes may also exert their effect independently of the environment. Whereas the geneticist uses highly advanced, rapid, comprehensive technologies to assess even subtle changes in the human genome, the researcher interested in environmental exposures is often confronted with crude information obtained from questionnaires or interviews. There is thus substantial need to develop better tools for individual exposure assessment in all relevant environmental fields. Despite these limitations, a number of important gene-environment interactions have been identified. These interactions point to the biology of environmental exposures as the involved genetic variation is suggestive of certain underlying mechanisms. Furthermore, the identification of subjects who are particularly susceptible to environmental hazards through genetic analyses helps to estimate better the strength of effect of environmental exposures. Finally, the analysis of gene-environment interactions may result in a reconciliation of seemingly contradictory findings from studies not taking environmental exposures into account. (J Allergy Clin Immunol 2009;123:3-11.). asthma| genes| environment| interactions|glutathione-s-transferase| childhood asthma| tobacco-smoke| air-pollution| lung-function| bronchial hyperresponsiveness| respiratory health| ormdl3 expression| maternal smoking| immunoglobulin-e.	JAN-2009	asthma| genes| environment| interactions|glutathione-s-transferase| childhood asthma| tobacco-smoke| air-pollution| lung-function| bronchial hyperresponsiveness| respiratory health| ormdl3 expression| maternal smoking| immunoglobulin-e	von Mutius, E	Gene-environment interactions in asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Asthma; genes; environment; interactions	GLUTATHIONE-S-TRANSFERASE; CHILDHOOD ASTHMA; TOBACCO-SMOKE; AIR-POLLUTION; LUNG-FUNCTION; BRONCHIAL HYPERRESPONSIVENESS; RESPIRATORY HEALTH; ORMDL3 EXPRESSION; MATERNAL SMOKING; IMMUNOGLOBULIN-E	Asthma is a complex disease, and its incidence is determined by an intricate interplay of genetic and environmental factors. The Identification of novel genes for asthma suggests that many genes with small effect,; rather than few genes with strong effects contribute to the development of asthma. These genetic effects may in part differ with respect to a subject's environmental exposures, although some genes may also exert their effect independently of the environment. Whereas the geneticist uses highly advanced, rapid, comprehensive technologies to assess even subtle changes in the human genome, the researcher interested in environmental exposures is often confronted with crude information obtained from questionnaires or interviews. There is thus substantial need to develop better tools for individual exposure assessment in all relevant environmental fields. Despite these limitations, a number of important gene-environment interactions have been identified. These interactions point to the biology of environmental exposures as the involved genetic variation is suggestive of certain underlying mechanisms. Furthermore, the identification of subjects who are particularly susceptible to environmental hazards through genetic analyses helps to estimate better the strength of effect of environmental exposures. Finally, the analysis of gene-environment interactions may result in a reconciliation of seemingly contradictory findings from studies not taking environmental exposures into account. (J Allergy Clin Immunol 2009;123:3-11.)	80	107	2009	9	10.1016/j.jaci.2008.10.046	Allergy; Immunology
Several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge. Background: On cross-linking of receptor-bound IgE antibodies by allergens, effector cells (basophils and mast cells) involved in type I allergic reactions degranulate and release the potent chemical mediators stored inside their granules. Total and allergen-specific IgE concentrations, IgE affinity for allergen, and IgE clonality are all distinct properties of allergic patients' IgE repertoires. However, the inability to isolate individual IgE antibodies from allergic patients' sera presents a major barrier to understanding the importance of patient-specific IgE repertoires for the manifestation and severity of allergic symptoms. Objective: We sought to investigate how individual properties of an IgE repertoire affect effector cell degranulation. Methods: A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized in regard to Der p 2 affinity, as well as Der p 2 epitope specificity, by using surface plasmon resonance technology. Human basophils were sensitized with different combinations of rIgEs, and degranulation responses were measured by means of flow cytometry after challenge with Der p 2. Results: A total of 31 Der p 2-specific rIgEs were produced. They bound a total of 9 different Der p 2 epitopes in the affinity range (KD value) of 0.0358 to 291 nM. Factors increasing human basophil degranulation were increased total IgE concentrations, increased concentrations of allergen-specific IgE relative to non-allergen-specific IgE, more even concentration of individual allergen-specific IgE clones, increased IgE affinity for allergen, and increased number of allergen epitopes recognized by the IgE repertoire (increased IgE clonality). Conclusion: This study demonstrates how distinct properties of the IgE repertoire, such as total and allergen-specific IgE antibody concentration, IgE affinity, and IgE clonality, affect effector cell degranulation.. allergy| recombinant ige| human ige| chimeric ige| antibody| affinity| epitope| allergen| der p 2| effector cell degranulation| basophil activation test| basophils| diagnosis|human basophil activation| histamine-release| cross-reactivity| leukemia-cells| mite allergen| anti-ige| affinity| immunoassay| expression| epitopes.	AUG-2008	allergy| recombinant ige| human ige| chimeric ige| antibody| affinity| epitope| allergen| der p 2| effector cell degranulation| basophil activation test| basophils| diagnosis|human basophil activation| histamine-release| cross-reactivity| leukemia-cells| mite allergen| anti-ige| affinity| immunoassay| expression| epitopes	Christensen, LH; Holm, J; Lund, G; Riise, E; Lund, K	Several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; recombinant IgE; human IgE; chimeric IgE; antibody; affinity; epitope; allergen; Der p 2; effector cell degranulation; basophil activation test; basophils; diagnosis	HUMAN BASOPHIL ACTIVATION; HISTAMINE-RELEASE; CROSS-REACTIVITY; LEUKEMIA-CELLS; MITE ALLERGEN; ANTI-IGE; AFFINITY; IMMUNOASSAY; EXPRESSION; EPITOPES	Background: On cross-linking of receptor-bound IgE antibodies by allergens, effector cells (basophils and mast cells) involved in type I allergic reactions degranulate and release the potent chemical mediators stored inside their granules. Total and allergen-specific IgE concentrations, IgE affinity for allergen, and IgE clonality are all distinct properties of allergic patients' IgE repertoires. However, the inability to isolate individual IgE antibodies from allergic patients' sera presents a major barrier to understanding the importance of patient-specific IgE repertoires for the manifestation and severity of allergic symptoms. Objective: We sought to investigate how individual properties of an IgE repertoire affect effector cell degranulation. Methods: A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized in regard to Der p 2 affinity, as well as Der p 2 epitope specificity, by using surface plasmon resonance technology. Human basophils were sensitized with different combinations of rIgEs, and degranulation responses were measured by means of flow cytometry after challenge with Der p 2. Results: A total of 31 Der p 2-specific rIgEs were produced. They bound a total of 9 different Der p 2 epitopes in the affinity range (KD value) of 0.0358 to 291 nM. Factors increasing human basophil degranulation were increased total IgE concentrations, increased concentrations of allergen-specific IgE relative to non-allergen-specific IgE, more even concentration of individual allergen-specific IgE clones, increased IgE affinity for allergen, and increased number of allergen epitopes recognized by the IgE repertoire (increased IgE clonality). Conclusion: This study demonstrates how distinct properties of the IgE repertoire, such as total and allergen-specific IgE antibody concentration, IgE affinity, and IgE clonality, affect effector cell degranulation.	28	107	2008	7	10.1016/j.jaci.2008.05.026	Allergy; Immunology
Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study. Background: Sublingual immunotherapy (SLIT) has been proved to be effective in allergic rhinitis and asthma, but there are few data on its preventive effects, especially in children. Objective: To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations, clinical symptoms, and bronchial hyperreactivity. Methods: A total of 216 children with allergic rhinitis, with or without intermittent asthma, were evaluated and then randomized to receive drugs alone or drugs plus SLIT openly for 3 years. The clinical score was assessed yearly during allergen exposure. Pulmonary function testing, methacholine challenge, and skin prick testing were performed at the beginning and end of the study. Results: One hundred forty-four children received SLIT and 72 received drugs only. Dropouts were 9.7% in the SLIT group and 8.3% in the controls. New sensitizations appeared in 34.8% of controls and in 3.1% of SLIT patients (odds ratio, 16.85; 95% confidence interval, 5.73-49.13). Mild persistent asthma was less frequent in SLIT patients (odds ratio, 0.04; 95% confidence interval, 0.01-0.17). There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year. The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group. Adherence was 80% or higher in 73.8% of patients. Only 1 patient reported systemic itching. Conclusions: In everyday clinical practice, SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy.. house-dust mite| allergic rhinitis| long-term| pediatric-patients| respiratory allergy| real-life| follow-up| children| asthma| efficacy.	AUG-2008	house-dust mite| allergic rhinitis| long-term| pediatric-patients| respiratory allergy| real-life| follow-up| children| asthma| efficacy	Marogna, M; Tomassetti, D; Bernasconi, A; Colombo, F; Massolo, A; Businco, ADR; Canonica, GW; Passalacqua, G; Tripodi, S	Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		HOUSE-DUST MITE; ALLERGIC RHINITIS; LONG-TERM; PEDIATRIC-PATIENTS; RESPIRATORY ALLERGY; REAL-LIFE; FOLLOW-UP; CHILDREN; ASTHMA; EFFICACY	Background: Sublingual immunotherapy (SLIT) has been proved to be effective in allergic rhinitis and asthma, but there are few data on its preventive effects, especially in children. Objective: To evaluate the clinical and preventive effects of SLIT in children by assessing onset of persistent asthma and new sensitizations, clinical symptoms, and bronchial hyperreactivity. Methods: A total of 216 children with allergic rhinitis, with or without intermittent asthma, were evaluated and then randomized to receive drugs alone or drugs plus SLIT openly for 3 years. The clinical score was assessed yearly during allergen exposure. Pulmonary function testing, methacholine challenge, and skin prick testing were performed at the beginning and end of the study. Results: One hundred forty-four children received SLIT and 72 received drugs only. Dropouts were 9.7% in the SLIT group and 8.3% in the controls. New sensitizations appeared in 34.8% of controls and in 3.1% of SLIT patients (odds ratio, 16.85; 95% confidence interval, 5.73-49.13). Mild persistent asthma was less frequent in SLIT patients (odds ratio, 0.04; 95% confidence interval, 0.01-0.17). There was a significant decrease in clinical scores in the SLIT group vs the control group since the first year. The number of children with a positive methacholine challenge result decreased significantly after 3 years only in the SLIT group. Adherence was 80% or higher in 73.8% of patients. Only 1 patient reported systemic itching. Conclusions: In everyday clinical practice, SLIT reduced the onset of new sensitizations and mild persistent asthma and decreased bronchial hyperreactivity in children with respiratory allergy.	34	107	2008	6		Allergy; Immunology
The use of household cleaning sprays and adult asthma - An international longitudinal study. Rationale Cleaning work and professional use of certain cleaning products have been associated with asthma, but respiratory effects of nonprofessional home cleaning have rarely been studied. Objectives: To investigate the risk of new-onset asthma in relation to the use of common household cleaners. Methods: Within the follow-up of the European Community Respiratory Health Survey in 10 countries, we identified 3,503 persons doing the cleaning in their homes and who were free of asthma at baseline. Frequency of use of 15 types of cleaning products was obtained in a face-to-face interview at follow-up. We studied the incidence of asthma defined as physician diagnosis and as symptoms or medication usage at follow-up. Associations between asthma and the use of cleaning products were evaluated using multivariable Cox proportional hazards or log-binomial regression analysis. Measurements and Main Results: The use of cleaning sprays at least weekly (42 70 of participants) was associated with the incidence of asthma symptoms or medication (relative risk [RR], 1.49; 95070 confidence interval [Cl], 1.12-1.99) and wheeze (RR, 1.39; 95 % Cl, 1.06-1.80). The incidence of physician-diagnosed asthma was higher among those using sprays at least 4 days per week (RR, 2.11; 95% Cl, 1.15-3.89). These associations were consistent for subgroups and not modified by atopy. Dose-response relationships (P < 0.05) were apparent for the frequency of use and the number of different sprays. Risks were predominantly found for the commonly used glass-cleaning, furniture, and air-refreshing sprays. Cleaning products not applied in spray form were not associated with asthma. Conclusions: Frequent use of common household cleaning sprays may be an important risk factor for adult asthma.. airway irritants| epidemiology| incidence| ecrhs|respiratory health survey| hydrochloric-acid| exposure| cleaners| products| risk| symptoms| mixture.	OCT 15-2007	airway irritants| epidemiology| incidence| ecrhs|respiratory health survey| hydrochloric-acid| exposure| cleaners| products| risk| symptoms| mixture	Zock, JP; Plana, E; Jarvis, D; Anto, JM; Kromhout, H; Kennedys, SM; Kuenzli, N; Villani, S; Olivieri, M; Toren, K; Radon, K; Sunyer, J; Dahlman-Hoglund, A; Norbaeck, D; Kogevinas, M	The use of household cleaning sprays and adult asthma - An international longitudinal study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	airway irritants; epidemiology; incidence; ECRHS	RESPIRATORY HEALTH SURVEY; HYDROCHLORIC-ACID; EXPOSURE; CLEANERS; PRODUCTS; RISK; SYMPTOMS; MIXTURE	Rationale Cleaning work and professional use of certain cleaning products have been associated with asthma, but respiratory effects of nonprofessional home cleaning have rarely been studied. Objectives: To investigate the risk of new-onset asthma in relation to the use of common household cleaners. Methods: Within the follow-up of the European Community Respiratory Health Survey in 10 countries, we identified 3,503 persons doing the cleaning in their homes and who were free of asthma at baseline. Frequency of use of 15 types of cleaning products was obtained in a face-to-face interview at follow-up. We studied the incidence of asthma defined as physician diagnosis and as symptoms or medication usage at follow-up. Associations between asthma and the use of cleaning products were evaluated using multivariable Cox proportional hazards or log-binomial regression analysis. Measurements and Main Results: The use of cleaning sprays at least weekly (42 70 of participants) was associated with the incidence of asthma symptoms or medication (relative risk [RR], 1.49; 95070 confidence interval [Cl], 1.12-1.99) and wheeze (RR, 1.39; 95 % Cl, 1.06-1.80). The incidence of physician-diagnosed asthma was higher among those using sprays at least 4 days per week (RR, 2.11; 95% Cl, 1.15-3.89). These associations were consistent for subgroups and not modified by atopy. Dose-response relationships (P < 0.05) were apparent for the frequency of use and the number of different sprays. Risks were predominantly found for the commonly used glass-cleaning, furniture, and air-refreshing sprays. Cleaning products not applied in spray form were not associated with asthma. Conclusions: Frequent use of common household cleaning sprays may be an important risk factor for adult asthma.	24	107	2007	7	10.1164/rccm.200612-17930C	General & Internal Medicine; Respiratory System
Fraction of exhaled nitric oxide at 50 mL/s - Reference values for adult lifelong never-smokers. Background: The measurement of fractional exhaled nitric oxide (FENO) is used as a marker of airway inflammation. The aim of this study was to establish reference values of FENO for adults. Methods: FENO at a flow rate of 50 mL/s was analyzed in 3,376 adults using a chemiluminescence analyzer according to American Thoracic Society/European Respiratory Society guidelines. Blood samples were analyzed, and atopy was defined as the presence of specific IgE. All subjects responded to a respiratory questionnaire. Those who had never smoked (n = 1,803) were selected for this study. After the exclusion of subjects with physician-diagnosed asthma, asthma symptoms, ever wheezing, dry cough, or use of inhaled steroids, 1,131 healthy never-smokers remained, including 845 nonatopic and 286 atopic subjects. Results: Based on multiple regression modeling, we propose the following reference equation for healthy never-smoking adults: Ln(FENO) = 0.057 + 0.013 x height (in centimeters) + 0.0088 x age (in years). The residual SD was 0.51, and the explanatory value was 9%. In a model, based on nonatopic subjects alone, the reference equation obtained was slightly different, as follows: Ln(FENO) = -0.0026 + 0.013 x height (in centimeters) + 0.010 x age (in years). The residual SD for this equation was 0.48, and the explanatory value was 11%. Conclusions: Normal values of FENO for adults may be predicted on the basis of age and height. However, as the reference equations only account for about 9 to 11% of the variation, the most important information that could be extracted from the study is that the upper limits of FENO range from 24.0 to 54.0 parts per billion, depending on age and height.. allergy| asthma| practice|age| air| sensitization| symptoms| children| height| asthma| atopy.	JUN-2007	allergy| asthma| practice|age| air| sensitization| symptoms| children| height| asthma| atopy	Olin, AC; Bake, B; Toren, K	Fraction of exhaled nitric oxide at 50 mL/s - Reference values for adult lifelong never-smokers		CHEST	allergy; asthma; practice	AGE; AIR; SENSITIZATION; SYMPTOMS; CHILDREN; HEIGHT; ASTHMA; ATOPY	Background: The measurement of fractional exhaled nitric oxide (FENO) is used as a marker of airway inflammation. The aim of this study was to establish reference values of FENO for adults. Methods: FENO at a flow rate of 50 mL/s was analyzed in 3,376 adults using a chemiluminescence analyzer according to American Thoracic Society/European Respiratory Society guidelines. Blood samples were analyzed, and atopy was defined as the presence of specific IgE. All subjects responded to a respiratory questionnaire. Those who had never smoked (n = 1,803) were selected for this study. After the exclusion of subjects with physician-diagnosed asthma, asthma symptoms, ever wheezing, dry cough, or use of inhaled steroids, 1,131 healthy never-smokers remained, including 845 nonatopic and 286 atopic subjects. Results: Based on multiple regression modeling, we propose the following reference equation for healthy never-smoking adults: Ln(FENO) = 0.057 + 0.013 x height (in centimeters) + 0.0088 x age (in years). The residual SD was 0.51, and the explanatory value was 9%. In a model, based on nonatopic subjects alone, the reference equation obtained was slightly different, as follows: Ln(FENO) = -0.0026 + 0.013 x height (in centimeters) + 0.010 x age (in years). The residual SD for this equation was 0.48, and the explanatory value was 11%. Conclusions: Normal values of FENO for adults may be predicted on the basis of age and height. However, as the reference equations only account for about 9 to 11% of the variation, the most important information that could be extracted from the study is that the upper limits of FENO range from 24.0 to 54.0 parts per billion, depending on age and height.	19	107	2007	5	10.1378/chest.06-2928	General & Internal Medicine; Respiratory System
"Accelerated antigen sampling and transport by airway mucosal dendritic cells following inhalation of a bacterial stimulus. An increase in the tempo of local dendritic cell (DC)-mediated immune surveillance is a recognized feature of the response to acute inflammation at airway mucosal surfaces, and transient up-regulation of the APC functions of these DC preceding their emigration to regional lymph nodes has recently been identified as an important trigger for T cell-mediated airway tissue damage in diseases such as asthma. In this study, using a rat model, we demonstrate that the kinetics of the airway mucosal DC (AMDC) response to challenge with heat-killed bacteria is considerably more rapid and as a consequence more effectively compartmentalized than that in recall responses to soluble Ag. Notably, Ag-bearing AMDC expressing full APC activity reach regional lymph nodes within 30 min of cessation of microbial exposure, and in contrast to recall responses to nonpathogenic Ags, there is no evidence of local expression of APC activity within the airway mucosa preceding DC emigration. We additionally demonstrate that, analogous to that reported in the gut, a subset of airway intraepithelial DC extend their processes into the airway lumen. This function is constitutively expressed within the AMDC population, providing a mechanism for continuous immune surveillance of the airway luminal surface in the absence of ""danger"", signals.. inhaled antigen| lymph-nodes| responses| exposure| inhibition| induction| tolerance| asthma| phase| mice."	NOV 1-2006	inhaled antigen| lymph-nodes| responses| exposure| inhibition| induction| tolerance| asthma| phase| mice	Jahnsen, FL; Strickland, DH; Thomas, JA; Tobagus, IT; Napoli, S; Zosky, GR; Turner, DJ; Sly, PD; Stumbles, PA; Holt, PG	Accelerated antigen sampling and transport by airway mucosal dendritic cells following inhalation of a bacterial stimulus		JOURNAL OF IMMUNOLOGY		INHALED ANTIGEN; LYMPH-NODES; RESPONSES; EXPOSURE; INHIBITION; INDUCTION; TOLERANCE; ASTHMA; PHASE; MICE	"An increase in the tempo of local dendritic cell (DC)-mediated immune surveillance is a recognized feature of the response to acute inflammation at airway mucosal surfaces, and transient up-regulation of the APC functions of these DC preceding their emigration to regional lymph nodes has recently been identified as an important trigger for T cell-mediated airway tissue damage in diseases such as asthma. In this study, using a rat model, we demonstrate that the kinetics of the airway mucosal DC (AMDC) response to challenge with heat-killed bacteria is considerably more rapid and as a consequence more effectively compartmentalized than that in recall responses to soluble Ag. Notably, Ag-bearing AMDC expressing full APC activity reach regional lymph nodes within 30 min of cessation of microbial exposure, and in contrast to recall responses to nonpathogenic Ags, there is no evidence of local expression of APC activity within the airway mucosa preceding DC emigration. We additionally demonstrate that, analogous to that reported in the gut, a subset of airway intraepithelial DC extend their processes into the airway lumen. This function is constitutively expressed within the AMDC population, providing a mechanism for continuous immune surveillance of the airway luminal surface in the absence of ""danger"", signals."	19	107	2006	7		Immunology
Carbon in airway macrophages and lung function in children. Background Epidemiologic studies indirectly suggest that the inhalation of carbonaceous particulate matter impairs lung function in children. Using the carbon content of airway macrophages as a marker of individual exposure to particulate matter derived from fossil fuel, we sought direct evidence of this association. Methods Airway macrophages were obtained from healthy children through sputum induction, and the area of airway macrophages occupied by carbon was measured. Lung function was measured with the use of spirometry. We modeled the exposure to primary particulate matter ( PM) that is less than 10 mu m in aerodynamic diameter (PM10) at or near each child's home address. Linear regression was used to evaluate associations between carbon content of alveolar macrophages and variables that may affect individual exposure. To determine whether lung function that is reduced for other reasons is associated with an increase in the carbon content of airway macrophages, we also studied children with severe asthma. Results We were able to assess the carbon content of airway macrophages in 64 of 114 healthy children (56 percent). Each increase in primary PM10 of 1.0 mu g per cubic meter was associated with an increase of 0.10 mu m(2) (95 percent confidence interval, 0.01 to 0.18) in the carbon content of airway macrophages, and each increase of 1.0 mu m(2) in carbon content was associated with a reduction of 17 percent (95 percent confidence interval, 5.6 to 28.4 percent) in forced expiratory volume in one second, of 12.9 percent (95 percent confidence interval, 0.9 to 24.8 percent) in forced vital capacity, and of 34.7 percent ( 95 percent confidence interval, 11.3 to 58.1 percent) in the forced expiratory flow between 25 and 75 percent of the forced vital capacity. The carbon content of airway macrophages was lower in children with asthma than in healthy children. Conclusions There is a dose-dependent inverse association between the carbon content of airway macrophages and lung function in children. We found no evidence that reduced lung function itself causes an increase in carbon content.. fine-particle deposition| induced sputum| alveolar macrophages| physical-activity| pollution| asthma| inhalation| retention| exposure| cotinine.	JUL 6-2006	fine-particle deposition| induced sputum| alveolar macrophages| physical-activity| pollution| asthma| inhalation| retention| exposure| cotinine	Kulkarni, N; Pierse, N; Rushton, L; Grigg, J	Carbon in airway macrophages and lung function in children		NEW ENGLAND JOURNAL OF MEDICINE		FINE-PARTICLE DEPOSITION; INDUCED SPUTUM; ALVEOLAR MACROPHAGES; PHYSICAL-ACTIVITY; POLLUTION; ASTHMA; INHALATION; RETENTION; EXPOSURE; COTININE	Background Epidemiologic studies indirectly suggest that the inhalation of carbonaceous particulate matter impairs lung function in children. Using the carbon content of airway macrophages as a marker of individual exposure to particulate matter derived from fossil fuel, we sought direct evidence of this association. Methods Airway macrophages were obtained from healthy children through sputum induction, and the area of airway macrophages occupied by carbon was measured. Lung function was measured with the use of spirometry. We modeled the exposure to primary particulate matter ( PM) that is less than 10 mu m in aerodynamic diameter (PM10) at or near each child's home address. Linear regression was used to evaluate associations between carbon content of alveolar macrophages and variables that may affect individual exposure. To determine whether lung function that is reduced for other reasons is associated with an increase in the carbon content of airway macrophages, we also studied children with severe asthma. Results We were able to assess the carbon content of airway macrophages in 64 of 114 healthy children (56 percent). Each increase in primary PM10 of 1.0 mu g per cubic meter was associated with an increase of 0.10 mu m(2) (95 percent confidence interval, 0.01 to 0.18) in the carbon content of airway macrophages, and each increase of 1.0 mu m(2) in carbon content was associated with a reduction of 17 percent (95 percent confidence interval, 5.6 to 28.4 percent) in forced expiratory volume in one second, of 12.9 percent (95 percent confidence interval, 0.9 to 24.8 percent) in forced vital capacity, and of 34.7 percent ( 95 percent confidence interval, 11.3 to 58.1 percent) in the forced expiratory flow between 25 and 75 percent of the forced vital capacity. The carbon content of airway macrophages was lower in children with asthma than in healthy children. Conclusions There is a dose-dependent inverse association between the carbon content of airway macrophages and lung function in children. We found no evidence that reduced lung function itself causes an increase in carbon content.	38	107	2006	10	10.1056/NEJMoa052972	General & Internal Medicine
Characterization of Fc epsilon RI-bearing CD123(+) blood dendritic cell antigen-2(+) plasmacytoid dendritic cells in atopic dermatitis. Background: The high-affinity receptor for IgE (FcepsilonRI) on myeloid dendritic cells has been shown to play a major role in atopic dermatitis (AD). Plasmacytoid dendritic cells (pDCs), which are instrumental in the defense of viral infections, are present in reduced amounts in the skin of patients with AD, which is characterized by a high susceptibility to viral infections. Objective: We explored phenotypical and functional characteristics of pDC in the peripheral blood of patients with AD and healthy individuals. Methods: Blood dendritic cell antigen-2(+)CD123(+) pDCs were enriched from the peripheral blood of patients with AD and studied in functional assays. Results: Skin-homing molecules such as cutaneous lymphocyte antigen and L-selectin CD62L were expressed in lower levels on pDCs of patients with AD. pDCs expressed high amounts of IgE-occupied FcepsilonRI. Further, FcepsilonRI aggregation on pDCs impaired the surface expression of MHC I and II, induced the production of IL-10, and enhanced the apoptosis of pDCs. Importantly, FcepsilonRI preactivated pDC produced less IFN-alpha and IFN-beta after stimulation with CpG motifs and enhanced the outcome of immune responses of the T(H)2 type. Conclusion: From these data, we conclude that FcepsilonRI-bearing pDCs from patients with AD (1) are different from pDCs of healthy individuals, (2) might be important in the pathophysiology of AD, and (3) contribute to the enhanced susceptibility of patients with AD to viral infections.. plasmacytoid dendritic cells| ige| fc epsilon ri| atopic dermatitis| ifn-alpha/beta|epidermal langerhans cells| high-affinity receptor| peripheral-blood| allergen presentation| adaptive immunity| presenting cells| ige receptors| serum ige| interferon| expression.	AUG-2004	plasmacytoid dendritic cells| ige| fc epsilon ri| atopic dermatitis| ifn-alpha/beta|epidermal langerhans cells| high-affinity receptor| peripheral-blood| allergen presentation| adaptive immunity| presenting cells| ige receptors| serum ige| interferon| expression	Novak, N; Allam, JP; Hagemann, T; Jenneck, C; Laffer, S; Valenta, R; Kochan, J; Bieber, T	Characterization of Fc epsilon RI-bearing CD123(+) blood dendritic cell antigen-2(+) plasmacytoid dendritic cells in atopic dermatitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	plasmacytoid dendritic cells; IgE; Fc epsilon RI; atopic dermatitis; IFN-alpha/beta	EPIDERMAL LANGERHANS CELLS; HIGH-AFFINITY RECEPTOR; PERIPHERAL-BLOOD; ALLERGEN PRESENTATION; ADAPTIVE IMMUNITY; PRESENTING CELLS; IGE RECEPTORS; SERUM IGE; INTERFERON; EXPRESSION	Background: The high-affinity receptor for IgE (FcepsilonRI) on myeloid dendritic cells has been shown to play a major role in atopic dermatitis (AD). Plasmacytoid dendritic cells (pDCs), which are instrumental in the defense of viral infections, are present in reduced amounts in the skin of patients with AD, which is characterized by a high susceptibility to viral infections. Objective: We explored phenotypical and functional characteristics of pDC in the peripheral blood of patients with AD and healthy individuals. Methods: Blood dendritic cell antigen-2(+)CD123(+) pDCs were enriched from the peripheral blood of patients with AD and studied in functional assays. Results: Skin-homing molecules such as cutaneous lymphocyte antigen and L-selectin CD62L were expressed in lower levels on pDCs of patients with AD. pDCs expressed high amounts of IgE-occupied FcepsilonRI. Further, FcepsilonRI aggregation on pDCs impaired the surface expression of MHC I and II, induced the production of IL-10, and enhanced the apoptosis of pDCs. Importantly, FcepsilonRI preactivated pDC produced less IFN-alpha and IFN-beta after stimulation with CpG motifs and enhanced the outcome of immune responses of the T(H)2 type. Conclusion: From these data, we conclude that FcepsilonRI-bearing pDCs from patients with AD (1) are different from pDCs of healthy individuals, (2) might be important in the pathophysiology of AD, and (3) contribute to the enhanced susceptibility of patients with AD to viral infections.	38	107	2004	7	10.1016/j.jaci.2004.05.038	Allergy; Immunology
Relationship of serum antioxidants to asthma prevalence in youth. The relationship of serum vitamin E, beta-carotene, vitamin C, and selenium to asthma was investigated among 7,505 youth (4-16 years old) in the Third National Health and Nutrition Examination Survey. Logistic regression models adjusted for potentially confounding variables, which generally had no effect on the coefficients for the antioxidants. Serum vitamin E had little or no association with asthma. In separate models, a SD increase in beta-carotene (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.7, 1.0), vitamin C (OR, 0.8; 95% Cl, 0.7,0.9), and selenium (OR, 0.9; 95% Cl, 0.7, 1.1) was associated with a 10-20% reduction in asthma prevalence. Serum cotinine was used to identify youth with no cigarette smoke exposure and passive exposure (7%): Active smokers were too few to be studied further. The selenium-asthma association was stronger in youth who were smoke exposed (p = 0.075). A SD increase in selenium was associated with a 50% reduction in asthma prevalence (OR, 0.5; 95% Cl, 0.2, 1.4) in youth with passive smoke exposure compared with a 10% reduction in youth with no smoke exposure. The findings support an association of antioxidants with prevalent asthma, which for some antioxidants is stronger among children exposed to cigarette smoke.. antioxidants| asthma| child| second-hand smoke|nutrition examination survey| 3rd national-health| kappa-b activation| childhood asthma| reduced selenium| dietary factors| united-states| lung-function| vitamin-c| children.	FEB 1-2004	antioxidants| asthma| child| second-hand smoke|nutrition examination survey| 3rd national-health| kappa-b activation| childhood asthma| reduced selenium| dietary factors| united-states| lung-function| vitamin-c| children	Rubin, RN; Navon, L; Cassano, PA	Relationship of serum antioxidants to asthma prevalence in youth		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	antioxidants; asthma; child; second-hand smoke	NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; KAPPA-B ACTIVATION; CHILDHOOD ASTHMA; REDUCED SELENIUM; DIETARY FACTORS; UNITED-STATES; LUNG-FUNCTION; VITAMIN-C; CHILDREN	The relationship of serum vitamin E, beta-carotene, vitamin C, and selenium to asthma was investigated among 7,505 youth (4-16 years old) in the Third National Health and Nutrition Examination Survey. Logistic regression models adjusted for potentially confounding variables, which generally had no effect on the coefficients for the antioxidants. Serum vitamin E had little or no association with asthma. In separate models, a SD increase in beta-carotene (odds ratio [OR], 0.9; 95% confidence interval [CI], 0.7, 1.0), vitamin C (OR, 0.8; 95% Cl, 0.7,0.9), and selenium (OR, 0.9; 95% Cl, 0.7, 1.1) was associated with a 10-20% reduction in asthma prevalence. Serum cotinine was used to identify youth with no cigarette smoke exposure and passive exposure (7%): Active smokers were too few to be studied further. The selenium-asthma association was stronger in youth who were smoke exposed (p = 0.075). A SD increase in selenium was associated with a 50% reduction in asthma prevalence (OR, 0.5; 95% Cl, 0.2, 1.4) in youth with passive smoke exposure compared with a 10% reduction in youth with no smoke exposure. The findings support an association of antioxidants with prevalent asthma, which for some antioxidants is stronger among children exposed to cigarette smoke.	43	107	2004	6	10.1164/rccm.200301-055OC	General & Internal Medicine; Respiratory System
Pregnancy outcome after first trimester exposure to corticosteroids: a prospective controlled study. Objective: To evaluate the safety of glucocorticosteroids (GCS) in pregnancy. Study design: The Israeli Teratogen Information Service (TIS) prospectively collected and followed 311 pregnancies counseled regarding systemic use of different GCS in the first trimester. The rate of major congenital anomalies was compared to that of 790 controls who were counseled for non-teratogenic exposure. Results: The rate of major anomalies did not significantly differ between the groups [12/262 = 4.6% (GCS), 19/728 = 2.6% (control), P = 0.116]. There was no case of oral cleft and no pattern of anomalies among the GCS exposed group. Higher rates of miscarriages (11.5% versus 7.0%, P = 0.013) and preterm births (22.7% versus 10.8%, P < 0.001) were observed among the GCS exposed group compared to the controls. GCS exposed infants had a lower median birth weight [3080g versus 3290g, P < 0.001] and were born at an earlier median gestational age [39 weeks versus 40, P < 0.001] compared to the control. Conclusions: The present study supports that GCS do not represent a major teratogenic risk in humans. The study was powered to find a 2.5-fold increase in the overall rate of major anomalies. (C) 2003 Elsevier Inc. All rights reserved.. glucocorticosteroids| prednisone| pregnancy| congenital anomalies|systemic-lupus-erythematosus| children born| women| prednisone| therapy| humans| cohort| asthma| growth.	JAN-FEB-2004	glucocorticosteroids| prednisone| pregnancy| congenital anomalies|systemic-lupus-erythematosus| children born| women| prednisone| therapy| humans| cohort| asthma| growth	Gur, C; Diav-Citrin, O; Shechtman, S; Arnon, J; Ornoy, A	Pregnancy outcome after first trimester exposure to corticosteroids: a prospective controlled study		REPRODUCTIVE TOXICOLOGY	glucocorticosteroids; prednisone; pregnancy; congenital anomalies	SYSTEMIC-LUPUS-ERYTHEMATOSUS; CHILDREN BORN; WOMEN; PREDNISONE; THERAPY; HUMANS; COHORT; ASTHMA; GROWTH	Objective: To evaluate the safety of glucocorticosteroids (GCS) in pregnancy. Study design: The Israeli Teratogen Information Service (TIS) prospectively collected and followed 311 pregnancies counseled regarding systemic use of different GCS in the first trimester. The rate of major congenital anomalies was compared to that of 790 controls who were counseled for non-teratogenic exposure. Results: The rate of major anomalies did not significantly differ between the groups [12/262 = 4.6% (GCS), 19/728 = 2.6% (control), P = 0.116]. There was no case of oral cleft and no pattern of anomalies among the GCS exposed group. Higher rates of miscarriages (11.5% versus 7.0%, P = 0.013) and preterm births (22.7% versus 10.8%, P < 0.001) were observed among the GCS exposed group compared to the controls. GCS exposed infants had a lower median birth weight [3080g versus 3290g, P < 0.001] and were born at an earlier median gestational age [39 weeks versus 40, P < 0.001] compared to the control. Conclusions: The present study supports that GCS do not represent a major teratogenic risk in humans. The study was powered to find a 2.5-fold increase in the overall rate of major anomalies. (C) 2003 Elsevier Inc. All rights reserved.	32	107	2004	9	10.1016/j.reprotox.2003.10.007	Reproductive Biology; Toxicology
Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study. Background: Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy. Method: A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges). Results: In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)). Conclusion: Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.. house-dust mite| exposure| risk| intervention| prediction| prevalence| rhinitis| age.	JUN-2003	house-dust mite| exposure| risk| intervention| prediction| prevalence| rhinitis| age	Arshad, SH; Bateman, B; Matthews, SM	Primary prevention of asthma and atopy during childhood by allergen avoidance in infancy: a randomised controlled study		THORAX		HOUSE-DUST MITE; EXPOSURE; RISK; INTERVENTION; PREDICTION; PREVALENCE; RHINITIS; AGE	Background: Recent increases in the prevalence of asthma and atopy emphasise the need for devising effective methods for primary prevention in children at high risk of atopy. Method: A birth cohort of genetically at risk infants was recruited in 1990 to a randomised controlled study. Allergen avoidance measures were instituted from birth in the prophylactic group (n=58). Infants were either breast fed with mother on a low allergen diet or given an extensively hydrolysed formula. Exposure to house dust mite was reduced by the use of an acaricide and mattress covers. The control group (n=62) followed standard advice as normally given by the health visitors. At age 8, all 120 children completed a questionnaire and 110 (92%) had all assessments (skin prick test, spirometry, and bronchial challenges). Results: In the prophylactic group eight children (13.8%) had current wheeze compared with 17 (27.4%) in the control group (p=0.08). Respective figures were eight (13.8%) and 20 (32.3%) for nocturnal cough (p=0.02) and 11 of 55 (20.0%) and 29 of 62 (46.8%) for atopy (p=0.003). After adjusting for confounding variables, the prophylactic group was found to be at a significantly reduced risk for current wheeze (odds ratio (OR) 0.26 (95% confidence interval (CI) 0.07 to 0.96)), nocturnal cough (OR 0.22 (95% CI 0.06 to 0.83)), asthma as defined by wheeze and bronchial hyperresponsiveness (OR 0.11 (95% CI 0.01 to 1.02)), and atopy (OR 0.21 (95% CI 0.07 to 0.62)). Conclusion: Strict allergen avoidance in infancy in high risk children reduces the development of allergic sensitisation to house dust mite. Our results suggest that this may prevent some cases of childhood asthma.	27	107	2003	5	10.1136/thorax.58.6.489	Respiratory System
Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years. Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheezing in the first 6 years of life among 453 children with parental history of atopy followed from birth. Among all study participants, day care in the first year of life was inversely associated with eczema (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1-0.8). Day care attendance in early life was associated with a decreased risk of asthma (OR = 0.3, 95% CI = 0.1-0.7) and recurrent wheezing (OR = 0.3, 95% CI = 0.1-0.9) at the age of 6 years and with a decreased risk of any wheezing after the age of 4 years only among children without maternal history of asthma. Among children with maternal history of asthma, day care in early life had no protective effect on asthma or recurrent wheezing at the age of 6 years but was instead associated with an increased risk of wheezing in the first 6 years of life. Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma.. day care| maternal history| asthma|lower respiratory illness| house-dust endotoxin| early-childhood| school-age| risk| exposure| children| wheeze| sensitization| cockroach.	MAY 1-2003	day care| maternal history| asthma|lower respiratory illness| house-dust endotoxin| early-childhood| school-age| risk| exposure| children| wheeze| sensitization| cockroach	Celedon, JC; Wright, RJ; Litonjua, AA; Sredl, D; Ryan, L; Weiss, ST; Gold, DR	Day care attendance in early life, maternal history of asthma, and asthma at the age of 6 years		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	day care; maternal history; asthma	LOWER RESPIRATORY ILLNESS; HOUSE-DUST ENDOTOXIN; EARLY-CHILDHOOD; SCHOOL-AGE; RISK; EXPOSURE; CHILDREN; WHEEZE; SENSITIZATION; COCKROACH	Among children not selected on the basis of a parental history of atopy, day care attendance in early life is inversely associated with asthma at school age. We examined the relation between day care in the first year of life and asthma, recurrent wheezing, and eczema at the age of 6 years and wheezing in the first 6 years of life among 453 children with parental history of atopy followed from birth. Among all study participants, day care in the first year of life was inversely associated with eczema (odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.1-0.8). Day care attendance in early life was associated with a decreased risk of asthma (OR = 0.3, 95% CI = 0.1-0.7) and recurrent wheezing (OR = 0.3, 95% CI = 0.1-0.9) at the age of 6 years and with a decreased risk of any wheezing after the age of 4 years only among children without maternal history of asthma. Among children with maternal history of asthma, day care in early life had no protective effect on asthma or recurrent wheezing at the age of 6 years but was instead associated with an increased risk of wheezing in the first 6 years of life. Our findings suggest that maternal history of asthma influences the relation between day care-related exposures and childhood asthma.	24	107	2003	5	10.1164/rccm.200209-1063OC	General & Internal Medicine; Respiratory System
Recombinant allergens promote expression of CD203c on basophils in sensitized individuals. Background: Traditionally, the diagnosis of type I allergies is based on clinical data, skin test results, and laboratory test results with allergen extracts. During the past few years, several attempts have been made to refine diagnostic assays in clinical allergy by introducing recombinant allergens and novel markers of IgE-dependent cell activation. Objectives: We have identified the ectoenzyme CD203c as a novel basophil antigen that is upregulated on IgE receptor cross-linkage. In this study A e applied CD203c and a panel of recombinant allergens to establish a novel basophil test that,allows for a reliable quantification of IgE-dependent responses at the effector cell level. Methods: Patients allergic to birch (Bet v, 1, n = 15; Bet v 2, n := 8) and grass (Phl p 1, n = 15; Phl p 2, n = 10; Phl p 5, n = 14) pollen allergens, as well as 10 nonallergic donors, were examined. Basophils were exposed to various concentrations of recombinant allergens for 15 minutes and then examined for expression of CD203c by means of flow cytometry. CD203c upregulation was correlated with the increase in CD63. Results: Exposure to recombinant allergens resulted in a dose-dependent increase in expression of CD203c on peripheral blood basophils in sensitized individuals, whereas no increase,was seen in healthy control subjects. The effects of the recombinant allergens on CD203c expression were also time dependent. There was a good correlation between allergen-induced upregulation of CD203c and upregulation of CD63 (R = 0.76). Conclusion: Flow cytometric quantitation of CD203c on blood basophils exposed to recombinant allergens is a useful approach to determine the allergic state in sensitized individuals and represents a basis for a sensitive novel allergy test.. basophils| allergy| recombinant allergens| diagnostic test| e-npp3| cd203c|fc-epsilon-ri| histamine-release| pollen allergens| blood basophils| antibody 97a6| activation| grass| ige| diagnosis| cyclosporine.	JUL-2002	basophils| allergy| recombinant allergens| diagnostic test| e-npp3| cd203c|fc-epsilon-ri| histamine-release| pollen allergens| blood basophils| antibody 97a6| activation| grass| ige| diagnosis| cyclosporine	Hauswirth, AW; Natter, S; Ghannadan, M; Majlesi, Y; Schernthaner, GH; Sperr, WR; Buhring, HJ; Valenta, R; Valent, P	Recombinant allergens promote expression of CD203c on basophils in sensitized individuals		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	basophils; allergy; recombinant allergens; diagnostic test; E-NPP3; CD203c	FC-EPSILON-RI; HISTAMINE-RELEASE; POLLEN ALLERGENS; BLOOD BASOPHILS; ANTIBODY 97A6; ACTIVATION; GRASS; IGE; DIAGNOSIS; CYCLOSPORINE	Background: Traditionally, the diagnosis of type I allergies is based on clinical data, skin test results, and laboratory test results with allergen extracts. During the past few years, several attempts have been made to refine diagnostic assays in clinical allergy by introducing recombinant allergens and novel markers of IgE-dependent cell activation. Objectives: We have identified the ectoenzyme CD203c as a novel basophil antigen that is upregulated on IgE receptor cross-linkage. In this study A e applied CD203c and a panel of recombinant allergens to establish a novel basophil test that,allows for a reliable quantification of IgE-dependent responses at the effector cell level. Methods: Patients allergic to birch (Bet v, 1, n = 15; Bet v 2, n := 8) and grass (Phl p 1, n = 15; Phl p 2, n = 10; Phl p 5, n = 14) pollen allergens, as well as 10 nonallergic donors, were examined. Basophils were exposed to various concentrations of recombinant allergens for 15 minutes and then examined for expression of CD203c by means of flow cytometry. CD203c upregulation was correlated with the increase in CD63. Results: Exposure to recombinant allergens resulted in a dose-dependent increase in expression of CD203c on peripheral blood basophils in sensitized individuals, whereas no increase,was seen in healthy control subjects. The effects of the recombinant allergens on CD203c expression were also time dependent. There was a good correlation between allergen-induced upregulation of CD203c and upregulation of CD63 (R = 0.76). Conclusion: Flow cytometric quantitation of CD203c on blood basophils exposed to recombinant allergens is a useful approach to determine the allergic state in sensitized individuals and represents a basis for a sensitive novel allergy test.	33	107	2002	8	10.1067/mai.2002.125257	Allergy; Immunology
Exhaled nitric oxide as a diagnostic test for asthma - Online versus offline techniques and effect of flow rate. Measurement of the fraction of exhaled nitric oxide (FENO) has been proposed as a noninvasive assessment of asthmatic airway inflammation. The influence of the expiratory flow rate during the collection maneuver on the ability of FENO to discriminate healthy subjects from those with asthma is unknown. We compared online and offline measurement of FENO at different flow rates. FENO was collected with expiratory flows of 50-500 ml/second in 34 patients with asthma (PC20 of less than 8 mg/ml) and 28 healthy subjects (PC20 of more than 10 mg/ml) using offline collection techniques. In a subgroup of 18 individuals with asthma and 17 healthy subjects, we additionally measured FENO at multiple expiratory flow rates (47-250 ml/second) using online methods. FENO fell with an increasing expiratory flow rate; FENO was higher in subjects with asthma as compared with healthy subjects at each flow rate studied with both techniques (p < 0.001). Receiver operating characteristic (ROC) curves for the diagnosis of asthma indicated that FENO is a robust discriminator between individuals with asthma and healthy subjects (area under the ROC curves 0.79 +/- 0.06 to 0.86 +/- 0.06, p for significant discrimination < 0.0001). Neither expiratory flow rate nor collection technique (online versus offline) significantly altered this discriminatory capacity (area under the ROC curves = 0.84 +/- 0.07 with the slowest online method versus 0.80 +/- 0.07 with the fastest offline method, p = 0.46). These data indicate that the choice of expiratory flow rate and collection method can be based on practicality and patient comfort without compromising the utility of this test for asthma.. nitric oxide| asthma| diagnosis|repeated spirometry| inhalation| collection| air| no.	JUN 15-2002	nitric oxide| asthma| diagnosis|repeated spirometry| inhalation| collection| air| no	Deykin, A; Massaro, AF; Drazen, JM; Israel, E	Exhaled nitric oxide as a diagnostic test for asthma - Online versus offline techniques and effect of flow rate		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	nitric oxide; asthma; diagnosis	REPEATED SPIROMETRY; INHALATION; COLLECTION; AIR; NO	Measurement of the fraction of exhaled nitric oxide (FENO) has been proposed as a noninvasive assessment of asthmatic airway inflammation. The influence of the expiratory flow rate during the collection maneuver on the ability of FENO to discriminate healthy subjects from those with asthma is unknown. We compared online and offline measurement of FENO at different flow rates. FENO was collected with expiratory flows of 50-500 ml/second in 34 patients with asthma (PC20 of less than 8 mg/ml) and 28 healthy subjects (PC20 of more than 10 mg/ml) using offline collection techniques. In a subgroup of 18 individuals with asthma and 17 healthy subjects, we additionally measured FENO at multiple expiratory flow rates (47-250 ml/second) using online methods. FENO fell with an increasing expiratory flow rate; FENO was higher in subjects with asthma as compared with healthy subjects at each flow rate studied with both techniques (p < 0.001). Receiver operating characteristic (ROC) curves for the diagnosis of asthma indicated that FENO is a robust discriminator between individuals with asthma and healthy subjects (area under the ROC curves 0.79 +/- 0.06 to 0.86 +/- 0.06, p for significant discrimination < 0.0001). Neither expiratory flow rate nor collection technique (online versus offline) significantly altered this discriminatory capacity (area under the ROC curves = 0.84 +/- 0.07 with the slowest online method versus 0.80 +/- 0.07 with the fastest offline method, p = 0.46). These data indicate that the choice of expiratory flow rate and collection method can be based on practicality and patient comfort without compromising the utility of this test for asthma.	28	107	2002	5	10.1164/rccm.2201081	General & Internal Medicine; Respiratory System
Pets and vermin are associated with high endotoxin levels in house dust. Background Previous studies have shown that the risk for allergic sensitization is lower in children who grew up on farms and in young adults who were exposed to dogs in early childhood. A higher microbial exposure in general and in particular to endotoxin in early childhood might contribute to this lower risk of atopy. Objective We examined whether the presence of pets or vermin in the home is associated with higher endotoxin concentrations in settled house dust. Methods House dust was sampled in a standardized manner on the living room floors of 454 homes of German children aged 5-10 years (participation rate 61%). Endotoxin was assessed with a quantitative kinetic chromogenic Limulus Amebocyte Lysate (LAL) method. Associations between endotoxin levels, pets and vermin are presented as ratios of the crude and confounder adjusted geometric means (means ratios) in the category of study vs. a reference category using multiple linear regression models. Results Endotoxin concentrations in living room floor dust sampled in homes without pets and vermin were lower (1246 ng per square meter, 1519 no, endotoxin/g dust, n = 157) than those sampled in homes with pets or vermin (2267 ng per square meter, 2200 ng endotoxin/g dust, n = 296). After adjustment for city of residence, season of dust sampling, age of the building and story of the dwelling, means ratios for endotoxin expressed per gram of dust were statistically significantly increased for dog (1.64, 95% Cl 1.09-2.46), for cat (1.50, 95% CI 1.03-2.18) and for cockroach (3.01, 95% CI 1.37-6.60), whereas no major statistically significant associations were found for other pets, ants and mice. Conclusion Keeping a dog or, a cat in the home is consistent with higher exposure to endotoxin and might therefore contribute to the lower risk of atopy in later life.. pets| vermin| endotoxin| indoor factors| house dust|hay-fever| allergic sensitization| exposure| asthma| children| farmers| environment| community| severity| protect.	DEC-2001	pets| vermin| endotoxin| indoor factors| house dust|hay-fever| allergic sensitization| exposure| asthma| children| farmers| environment| community| severity| protect	Heinrich, J; Gehring, U; Douwes, J; Koch, A; Fahlbusch, B; Bischof, W; Wichmann, HE	Pets and vermin are associated with high endotoxin levels in house dust		CLINICAL AND EXPERIMENTAL ALLERGY	pets; vermin; endotoxin; indoor factors; house dust	HAY-FEVER; ALLERGIC SENSITIZATION; EXPOSURE; ASTHMA; CHILDREN; FARMERS; ENVIRONMENT; COMMUNITY; SEVERITY; PROTECT	Background Previous studies have shown that the risk for allergic sensitization is lower in children who grew up on farms and in young adults who were exposed to dogs in early childhood. A higher microbial exposure in general and in particular to endotoxin in early childhood might contribute to this lower risk of atopy. Objective We examined whether the presence of pets or vermin in the home is associated with higher endotoxin concentrations in settled house dust. Methods House dust was sampled in a standardized manner on the living room floors of 454 homes of German children aged 5-10 years (participation rate 61%). Endotoxin was assessed with a quantitative kinetic chromogenic Limulus Amebocyte Lysate (LAL) method. Associations between endotoxin levels, pets and vermin are presented as ratios of the crude and confounder adjusted geometric means (means ratios) in the category of study vs. a reference category using multiple linear regression models. Results Endotoxin concentrations in living room floor dust sampled in homes without pets and vermin were lower (1246 ng per square meter, 1519 no, endotoxin/g dust, n = 157) than those sampled in homes with pets or vermin (2267 ng per square meter, 2200 ng endotoxin/g dust, n = 296). After adjustment for city of residence, season of dust sampling, age of the building and story of the dwelling, means ratios for endotoxin expressed per gram of dust were statistically significantly increased for dog (1.64, 95% Cl 1.09-2.46), for cat (1.50, 95% CI 1.03-2.18) and for cockroach (3.01, 95% CI 1.37-6.60), whereas no major statistically significant associations were found for other pets, ants and mice. Conclusion Keeping a dog or, a cat in the home is consistent with higher exposure to endotoxin and might therefore contribute to the lower risk of atopy in later life.	30	107	2001	7	10.1046/j.1365-2222.2001.01220.x	Allergy; Immunology
Allergic fungal rhinosinusitis: Current theories and management strategies. The combination of nasal polyposis, crust formation, and sinus cultures yielding Aspergillus was first noted in 1976 by Safirstein,(1) who observed the clinical similarity that this constellation of findings shared with allergic bronchopulmonary Aspergillosis (ABPA). Eventually this disease came to be known as allergic fungal rhinosinusitis (AFS), As clinical evidence of AFS accumulated, controversy regarding its etiology, pathogenesis, natural history, and appropriate treatment naturally emerged. Despite past and current efforts, many of these controversies remain incompletely resolved, but continuing clinical study has illuminated some aspects of the disease and has Zed to an improved understanding of AFS and its treatment. Fungi associated with the development of AFS are ubiquitous and predominantly of the dematiaceous family, The eosinophilic host response to the presence of these fungi within the nose and paranasal sinuses gives rise to those clinical manifestations of the disease (nasal polyps, expansile mucocele formation, allergic fungal mucin, etc.). Exposure alone to these fungi, however, appears to be insufficient to initiate the disease. At the present time it is likely that initiation of the inflammatory cascade leading to AFS is a multifactorial event, requiring the simultaneous occurrence of such things as IgE-mediated sensitivity (atopy), specific T-cell HLA receptor expression, exposure to specific fungi, and aberration of local mucosal defense mechanisms. A variety of treatment plans for AFS have emerged, but the potential for recidivism remains well recognized, ranging from 10% to nearly 100% suggesting the need for continued study of this disease and fueling present controversy. This article is intended to review current data and theories regarding the pathophysiology of AFS, as well as the role of various surgical and nonsurgical forms of therapy.. fungus| allergy| rhinosinusitis|newly recognized form| aspergillus-sinusitis| surgical-management| immunotherapy| diagnosis| experience| organisms| therapy| disease| ct.	JUN-2001	fungus| allergy| rhinosinusitis|newly recognized form| aspergillus-sinusitis| surgical-management| immunotherapy| diagnosis| experience| organisms| therapy| disease| ct	Marple, BF	Allergic fungal rhinosinusitis: Current theories and management strategies		LARYNGOSCOPE	fungus; allergy; rhinosinusitis	NEWLY RECOGNIZED FORM; ASPERGILLUS-SINUSITIS; SURGICAL-MANAGEMENT; IMMUNOTHERAPY; DIAGNOSIS; EXPERIENCE; ORGANISMS; THERAPY; DISEASE; CT	The combination of nasal polyposis, crust formation, and sinus cultures yielding Aspergillus was first noted in 1976 by Safirstein,(1) who observed the clinical similarity that this constellation of findings shared with allergic bronchopulmonary Aspergillosis (ABPA). Eventually this disease came to be known as allergic fungal rhinosinusitis (AFS), As clinical evidence of AFS accumulated, controversy regarding its etiology, pathogenesis, natural history, and appropriate treatment naturally emerged. Despite past and current efforts, many of these controversies remain incompletely resolved, but continuing clinical study has illuminated some aspects of the disease and has Zed to an improved understanding of AFS and its treatment. Fungi associated with the development of AFS are ubiquitous and predominantly of the dematiaceous family, The eosinophilic host response to the presence of these fungi within the nose and paranasal sinuses gives rise to those clinical manifestations of the disease (nasal polyps, expansile mucocele formation, allergic fungal mucin, etc.). Exposure alone to these fungi, however, appears to be insufficient to initiate the disease. At the present time it is likely that initiation of the inflammatory cascade leading to AFS is a multifactorial event, requiring the simultaneous occurrence of such things as IgE-mediated sensitivity (atopy), specific T-cell HLA receptor expression, exposure to specific fungi, and aberration of local mucosal defense mechanisms. A variety of treatment plans for AFS have emerged, but the potential for recidivism remains well recognized, ranging from 10% to nearly 100% suggesting the need for continued study of this disease and fueling present controversy. This article is intended to review current data and theories regarding the pathophysiology of AFS, as well as the role of various surgical and nonsurgical forms of therapy.	62	107	2001	14	10.1097/00005537-200106000-00015	Research & Experimental Medicine; Otorhinolaryngology
Detection of peanut allergens in breast milk of lactating women. Context Most individuals who react to peanuts do so on their first known exposure. A potential but unproven route of occult exposure resulting in sensitization to peanut is via breast milk during lactation. Objective To investigate the ability of maternal dietary peanut protein to pass into breast milk during lactation, Design and Setting Clinical investigation conducted at 2 North American hospitals from March 1999 to October 2000, Patients Twenty-three healthy, lactating women aged 21 to 35 years. Intervention Each woman consumed 50 g of dry roasted peanuts, after which breast milk samples were collected at hourly intervals. Main Outcome Measures Presence in breast milk of total peanut protein, analyzed by a sandwich enzyme-linked immunosorbent assay, and 2 major peanut allergens, Ara h 1 and Ara h 2, detected by immunoblot analysis. Results Peanut protein was detected in 11 of 23 subjects, It was detected in 10 subjects within 2 hours of ingestion and in 1 subject within 6 hours. The median peak peanut protein concentration in breast milk was 200 ng/mL (mean, 222 ng/mL; range, 120-430 ng/mL). Both major peanut allergens Ara h 1 and Ara h 2 were detected. Conclusions Peanut protein is secreted into breast milk of lactating women following maternal dietary ingestion, Exposure to peanut protein during breastfeeding is a route of occult exposure that may result in sensitization of at-risk infants.. bovine beta-lactoglobulin| cows milk| maternal diet| nut allergy| fed infants| food| children| mothers| egg| hypersensitivity.	APR 4-2001	bovine beta-lactoglobulin| cows milk| maternal diet| nut allergy| fed infants| food| children| mothers| egg| hypersensitivity	Vadas, P; Wai, Y; Burks, W; Perelman, B	Detection of peanut allergens in breast milk of lactating women		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		BOVINE BETA-LACTOGLOBULIN; COWS MILK; MATERNAL DIET; NUT ALLERGY; FED INFANTS; FOOD; CHILDREN; MOTHERS; EGG; HYPERSENSITIVITY	Context Most individuals who react to peanuts do so on their first known exposure. A potential but unproven route of occult exposure resulting in sensitization to peanut is via breast milk during lactation. Objective To investigate the ability of maternal dietary peanut protein to pass into breast milk during lactation, Design and Setting Clinical investigation conducted at 2 North American hospitals from March 1999 to October 2000, Patients Twenty-three healthy, lactating women aged 21 to 35 years. Intervention Each woman consumed 50 g of dry roasted peanuts, after which breast milk samples were collected at hourly intervals. Main Outcome Measures Presence in breast milk of total peanut protein, analyzed by a sandwich enzyme-linked immunosorbent assay, and 2 major peanut allergens, Ara h 1 and Ara h 2, detected by immunoblot analysis. Results Peanut protein was detected in 11 of 23 subjects, It was detected in 10 subjects within 2 hours of ingestion and in 1 subject within 6 hours. The median peak peanut protein concentration in breast milk was 200 ng/mL (mean, 222 ng/mL; range, 120-430 ng/mL). Both major peanut allergens Ara h 1 and Ara h 2 were detected. Conclusions Peanut protein is secreted into breast milk of lactating women following maternal dietary ingestion, Exposure to peanut protein during breastfeeding is a route of occult exposure that may result in sensitization of at-risk infants.	23	107	2001	3	10.1001/jama.285.13.1746	General & Internal Medicine
Noninvasive detection of hydroxyl radical generation in lung by diesel exhaust particles. Diesel exhaust particles (DEP) induce pulmonary tumors, asthma-like symptoms, and the like in experimental animals. The involvement of reactive oxygen species (ROS) is suggested in the injuries induced by DEP, though the generation of ROS has not been proven. The present study provided the first direct evidence of (OH)-O-. generation in the lungs of living mice after intratracheal instillation of DEP, using noninvasive L-band ESR spectroscopy and a membrane-impermeable nitroxyl probe. (OH)-O-. generation is confirmed with the enhancement of in vivo ESR signal decay rate of the probe. The decay rate at mid-thorax was significantly enhanced in DEP-treated mice compared to that in vehicle-treated mice. The enhancement was completely suppressed by the administration of either (OH)-O-. scavengers, catalase, or desferrioxamine, while the administration of SOD further increased the rate. The administration of Fenton's reagents into the lung also enhanced the decay rate of the probe at mid-thorax of mice. These results clearly provided evidence that the intratracheal exposure to DEP in mice produced (OH)-O-. in the lung through an iron-catalyzed reaction of superoxide/H2O2. This first direct evidence of (OH)-O-. generation in DEP-treated mice lung may be utilized to determine treatments for DEP-induced lung injury. (C) 2001 Elsevier Science Inc.. l-band esr| diesel exhaust particles| nitroxide radical| lung| free radicals| reactive oxygen species| superoxide dismutase|respiratory-distress-syndrome| reactive oxygen metabolites| in-vivo esr| oxidative stress| whole mice| intratracheal instillation| resonance spectroscopy| nitroxide radicals| pulse-radiolysis| inspired oxygen.	MAR 1-2001	l-band esr| diesel exhaust particles| nitroxide radical| lung| free radicals| reactive oxygen species| superoxide dismutase|respiratory-distress-syndrome| reactive oxygen metabolites| in-vivo esr| oxidative stress| whole mice| intratracheal instillation| resonance spectroscopy| nitroxide radicals| pulse-radiolysis| inspired oxygen	Han, JY; Takeshita, K; Utsumi, H	Noninvasive detection of hydroxyl radical generation in lung by diesel exhaust particles		FREE RADICAL BIOLOGY AND MEDICINE	l-band ESR; diesel exhaust particles; nitroxide radical; lung; free radicals; reactive oxygen species; superoxide dismutase	RESPIRATORY-DISTRESS-SYNDROME; REACTIVE OXYGEN METABOLITES; IN-VIVO ESR; OXIDATIVE STRESS; WHOLE MICE; INTRATRACHEAL INSTILLATION; RESONANCE SPECTROSCOPY; NITROXIDE RADICALS; PULSE-RADIOLYSIS; INSPIRED OXYGEN	Diesel exhaust particles (DEP) induce pulmonary tumors, asthma-like symptoms, and the like in experimental animals. The involvement of reactive oxygen species (ROS) is suggested in the injuries induced by DEP, though the generation of ROS has not been proven. The present study provided the first direct evidence of (OH)-O-. generation in the lungs of living mice after intratracheal instillation of DEP, using noninvasive L-band ESR spectroscopy and a membrane-impermeable nitroxyl probe. (OH)-O-. generation is confirmed with the enhancement of in vivo ESR signal decay rate of the probe. The decay rate at mid-thorax was significantly enhanced in DEP-treated mice compared to that in vehicle-treated mice. The enhancement was completely suppressed by the administration of either (OH)-O-. scavengers, catalase, or desferrioxamine, while the administration of SOD further increased the rate. The administration of Fenton's reagents into the lung also enhanced the decay rate of the probe at mid-thorax of mice. These results clearly provided evidence that the intratracheal exposure to DEP in mice produced (OH)-O-. in the lung through an iron-catalyzed reaction of superoxide/H2O2. This first direct evidence of (OH)-O-. generation in DEP-treated mice lung may be utilized to determine treatments for DEP-induced lung injury. (C) 2001 Elsevier Science Inc.	60	107	2001	10	10.1016/S0891-5849(00)00501-3	Biochemistry & Molecular Biology; Endocrinology & Metabolism
The influence of lung deposition on clinical response. Delivery of more drug to the lung may appear to be a desirable goal in the treatment of asthma and chronic obstructive pulmonary disease, since only 10 to 15% of a drug dose administered via a metered dose inhaler (MDI) reaches the lung. However, increasing the dose of most inhaled drugs may only lead to an increase in side effects, since maximal clinical benefit is usually obtained with the currently recommended dosages. Improving the regional deposition of inhaled drugs may be a more effective way of modifying clinical response. Particle size is the most significant determinant of the deposition pattern of inhaled drugs. Optimum drug delivery to the conducting airways occurs with particles ranging from 2.5 to 6 mum; particles <2.5 <mu>m are deposited mainly in the alveoli where they may exert no pharmacodynamic effect and are rapidly absorbed, increasing the risk of systemic adverse events. Delivery devices can be compared by estimating the lung and systemic exposures, taking into account the efficacy and safety dose-response relationships for the drug-device combination. Current devices have profoundly different lung deposition profiles that could affect clinical efficacy when switching devices. Devices that achieve a high lung to systemic ratio for the inhaled drug are preferable.. asthma| chronic obstructive disease| lung deposition| efficacy| metered dose inhalers|beclomethasone dipropionate| budesonide| pharmacokinetics| turbuhaler(r)| terbutaline.	2001	asthma| chronic obstructive disease| lung deposition| efficacy| metered dose inhalers|beclomethasone dipropionate| budesonide| pharmacokinetics| turbuhaler(r)| terbutaline	Pritchard, JN	The influence of lung deposition on clinical response		JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG	asthma; chronic obstructive disease; lung deposition; efficacy; metered dose inhalers	BECLOMETHASONE DIPROPIONATE; BUDESONIDE; PHARMACOKINETICS; TURBUHALER(R); TERBUTALINE	Delivery of more drug to the lung may appear to be a desirable goal in the treatment of asthma and chronic obstructive pulmonary disease, since only 10 to 15% of a drug dose administered via a metered dose inhaler (MDI) reaches the lung. However, increasing the dose of most inhaled drugs may only lead to an increase in side effects, since maximal clinical benefit is usually obtained with the currently recommended dosages. Improving the regional deposition of inhaled drugs may be a more effective way of modifying clinical response. Particle size is the most significant determinant of the deposition pattern of inhaled drugs. Optimum drug delivery to the conducting airways occurs with particles ranging from 2.5 to 6 mum; particles <2.5 <mu>m are deposited mainly in the alveoli where they may exert no pharmacodynamic effect and are rapidly absorbed, increasing the risk of systemic adverse events. Delivery devices can be compared by estimating the lung and systemic exposures, taking into account the efficacy and safety dose-response relationships for the drug-device combination. Current devices have profoundly different lung deposition profiles that could affect clinical efficacy when switching devices. Devices that achieve a high lung to systemic ratio for the inhaled drug are preferable.	19	107	2001	8		Public, Environmental & Occupational Health; Respiratory System
Exposure to motor vehicle traffic and allergic sensitization. We examined the association between the presence of an allergic sensitization and seasonal allergic diseases or symptoms and the exposure to road traffic in Basel, Switzerland. Traffic counts at the domiciles of subjects ranged from 24 to 32,504 cars per 24 hours, with a median of 1,624. To investigate the relation of road traffic and allergies, we matched the data of the traffic inventory of Basel with those of the 820 participants of the SAPALDIA study (Swiss Study on Air Pollution and Lung Diseases in Adults), ages 18-60 years, who had completed a detailed respiratory health questionnaire and had undergone allergy testing (skin prick tests and serologic examinations). We observed a positive association with a sensitization to pollen that was most pronounced among persons with a duration of residence of at least 10 years. The odds ratios (adjusted for educational level, smoking behavior, number of siblings, age, sex, and family history of atopy) for cars, contrasting four exposure categories with the lowest quartile as referent category, were 1.99 [95% confidence interval (CI) = 0.91-4.38], 2.47 (95% CI = 1.06-5.73), and 2.83 (95% CI = 1.26-6.31). These results suggest that living on busy roads is associated with a higher risk for a sensitization to pollen and could possibly he interpreted as an indication for interactions between pollen and air pollutants. We did not, however, find a similar relation between motor vehicle traffic and hay fever or seasonal allergic symptoms, and we saw no trend that increasing traffic exposure was associated with a rise in sensitization rates to indoor allergens.. air pollution| allergies| pollen| traffic density|chronic respiratory symptoms| diesel exhaust particles| air-pollutants| adjuvant activity| asthma| pollution| children| mice| pollen| adults.	JUL-2000	air pollution| allergies| pollen| traffic density|chronic respiratory symptoms| diesel exhaust particles| air-pollutants| adjuvant activity| asthma| pollution| children| mice| pollen| adults	Wyler, C; Braun-Fahrlander, C; Kunzli, N; Schindler, C; Ackermann-Liebrich, U; Perruchoud, AP; Leuenberger, P; Wuthrich, B	Exposure to motor vehicle traffic and allergic sensitization		EPIDEMIOLOGY	air pollution; allergies; pollen; traffic density	CHRONIC RESPIRATORY SYMPTOMS; DIESEL EXHAUST PARTICLES; AIR-POLLUTANTS; ADJUVANT ACTIVITY; ASTHMA; POLLUTION; CHILDREN; MICE; POLLEN; ADULTS	We examined the association between the presence of an allergic sensitization and seasonal allergic diseases or symptoms and the exposure to road traffic in Basel, Switzerland. Traffic counts at the domiciles of subjects ranged from 24 to 32,504 cars per 24 hours, with a median of 1,624. To investigate the relation of road traffic and allergies, we matched the data of the traffic inventory of Basel with those of the 820 participants of the SAPALDIA study (Swiss Study on Air Pollution and Lung Diseases in Adults), ages 18-60 years, who had completed a detailed respiratory health questionnaire and had undergone allergy testing (skin prick tests and serologic examinations). We observed a positive association with a sensitization to pollen that was most pronounced among persons with a duration of residence of at least 10 years. The odds ratios (adjusted for educational level, smoking behavior, number of siblings, age, sex, and family history of atopy) for cars, contrasting four exposure categories with the lowest quartile as referent category, were 1.99 [95% confidence interval (CI) = 0.91-4.38], 2.47 (95% CI = 1.06-5.73), and 2.83 (95% CI = 1.26-6.31). These results suggest that living on busy roads is associated with a higher risk for a sensitization to pollen and could possibly he interpreted as an indication for interactions between pollen and air pollutants. We did not, however, find a similar relation between motor vehicle traffic and hay fever or seasonal allergic symptoms, and we saw no trend that increasing traffic exposure was associated with a rise in sensitization rates to indoor allergens.	35	107	2000	7	10.1097/00001648-200007000-00015	Public, Environmental & Occupational Health
International consensus on (ICON) pediatric asthma. Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.. asthma| children| consensus| guidelines| wheeze|inhaled fluticasone propionate| randomized controlled-trial| grass-pollen immunotherapy| nitric-oxide measurements| acting beta-agonists| house-dust mite| long-term| childhood asthma| airway hyperresponsiveness| preschool-children.	AUG-2012	asthma| children| consensus| guidelines| wheeze|inhaled fluticasone propionate| randomized controlled-trial| grass-pollen immunotherapy| nitric-oxide measurements| acting beta-agonists| house-dust mite| long-term| childhood asthma| airway hyperresponsiveness| preschool-children	Papadopoulos, NG; Arakawa, H; Carlsen, KH; Custovic, A; Gern, J; Lemanske, R; Le Souef, P; Makela, M; Roberts, G; Wong, G; Zar, H; Akdis, CA; Bacharier, LB; Baraldi, E; van Bever, HP; de Blic, J; Boner, A; Burks, W; Casale, TB; Castro-Rodriguez, JA; Chen, YZ; El-Gamal, YM; Everard, ML; Frischer, T; Geller, M; Gereda, J; Goh, DY; Guilbert, TW; Hedlin, G; Heymann, PW; Hong, SJ; Hossny, EM; Huang, JL; Jackson, DJ; de Jongste, JC; Kalayci, O; Ait-Khaled, N; Kling, S; Kuna, P; Lau, S; Ledford, DK; Lee, SI; Liu, AH; Lockey, RF; Lodrup-Carlsen, K; Lotvall, J; Morikawa, A; Nieto, A; Paramesh, H; Pawankar, R; Pohunek, P; Pongracic, J; Price, D; Robertson, C; Rosario, N; Rossenwasser, LJ; Sly, PD; Stein, R; Stick, S; Szefler, S; Taussig, LM; Valovirta, E; Vichyanond, P; Wallace, D; Weinberg, E; Wennergren, G; Wildhaber, J; Zeiger, RS	International consensus on (ICON) pediatric asthma		ALLERGY	asthma; children; consensus; guidelines; wheeze	INHALED FLUTICASONE PROPIONATE; RANDOMIZED CONTROLLED-TRIAL; GRASS-POLLEN IMMUNOTHERAPY; NITRIC-OXIDE MEASUREMENTS; ACTING BETA-AGONISTS; HOUSE-DUST MITE; LONG-TERM; CHILDHOOD ASTHMA; AIRWAY HYPERRESPONSIVENESS; PRESCHOOL-CHILDREN	Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.	142	106	2012	22	10.1111/j.1398-9995.2012.02865.x	Allergy; Immunology
SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. SCH527123 is a novel, selective CXC chemokine receptor 2 antagonist that inhibits neutrophil activation and modulates neutrophil trafficking in animal models, characteristics that may be beneficial in the treatment of conditions with unbalanced pulmonary neutrophilia, such as chronic obstructive pulmonary disease. The purpose of this proof-of-principle study was to determine whether SCH527123 inhibits ozone-induced neutrophil recruitment in healthy humans. In a randomised, double-blind, placebo-controlled, three-way crossover study, oral SCH527123 (50 mg once daily, 4 days), prednisolone (50 mg once), or placebo was alternated with 2-week washouts. 18 healthy ozone responders (>20% increase in sputum neutrophils) underwent ozone challenge tests (250 ppb, 3 h intermittent exercise) 1 h after the last treatment dose. Sputum was induced at 3 h post-challenge. After SCH527123 treatment, the ozone challenge resulted in significantly lower sputum neutrophil counts (0.13 x 10(6).mL(-1)) compared with prednisolone (0.84 x 10(6).mL(-1); p<0.001) or placebo (2.98 x 10(6).mL(-1); p<0.001). Comparable results were obtained for total cell count, percentage of sputum neutrophils, and for interleukin-8 and myeloperoxidase in sputum supernatant. Post-challenge, SCH527123 inhibited neutrophilia in peripheral blood but significantly less than in sputum. All treatments were safe and well tolerated. SCH527123 causes significant attenuation of ozone-induced airway neutrophilia in healthy subjects. Further evaluation in a large trial of patients with pulmonary disorders is warranted.. anti-inflammatory| chronic obstructive pulmonary disease| interleukin-8| myeloperoxidase| pharmacodynamics|obstructive pulmonary-disease| airway inflammation| histone deacetylase| activation markers| induced sputum| bone-marrow| asthma| copd| recruitment| exposures.	MAR-2010	anti-inflammatory| chronic obstructive pulmonary disease| interleukin-8| myeloperoxidase| pharmacodynamics|obstructive pulmonary-disease| airway inflammation| histone deacetylase| activation markers| induced sputum| bone-marrow| asthma| copd| recruitment| exposures	Holz, O; Khalilieh, S; Ludwig-Sengpiel, A; Watz, H; Stryszak, P; Soni, P; Tsai, M; Sadeh, J; Magnussen, H	SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects		EUROPEAN RESPIRATORY JOURNAL	Anti-inflammatory; chronic obstructive pulmonary disease; interleukin-8; myeloperoxidase; pharmacodynamics	OBSTRUCTIVE PULMONARY-DISEASE; AIRWAY INFLAMMATION; HISTONE DEACETYLASE; ACTIVATION MARKERS; INDUCED SPUTUM; BONE-MARROW; ASTHMA; COPD; RECRUITMENT; EXPOSURES	SCH527123 is a novel, selective CXC chemokine receptor 2 antagonist that inhibits neutrophil activation and modulates neutrophil trafficking in animal models, characteristics that may be beneficial in the treatment of conditions with unbalanced pulmonary neutrophilia, such as chronic obstructive pulmonary disease. The purpose of this proof-of-principle study was to determine whether SCH527123 inhibits ozone-induced neutrophil recruitment in healthy humans. In a randomised, double-blind, placebo-controlled, three-way crossover study, oral SCH527123 (50 mg once daily, 4 days), prednisolone (50 mg once), or placebo was alternated with 2-week washouts. 18 healthy ozone responders (>20% increase in sputum neutrophils) underwent ozone challenge tests (250 ppb, 3 h intermittent exercise) 1 h after the last treatment dose. Sputum was induced at 3 h post-challenge. After SCH527123 treatment, the ozone challenge resulted in significantly lower sputum neutrophil counts (0.13 x 10(6).mL(-1)) compared with prednisolone (0.84 x 10(6).mL(-1); p<0.001) or placebo (2.98 x 10(6).mL(-1); p<0.001). Comparable results were obtained for total cell count, percentage of sputum neutrophils, and for interleukin-8 and myeloperoxidase in sputum supernatant. Post-challenge, SCH527123 inhibited neutrophilia in peripheral blood but significantly less than in sputum. All treatments were safe and well tolerated. SCH527123 causes significant attenuation of ozone-induced airway neutrophilia in healthy subjects. Further evaluation in a large trial of patients with pulmonary disorders is warranted.	30	106	2010	7	10.1183/09031936.00048509	Respiratory System
Histone Deacetylase 2 Is Phosphorylated, Ubiquitinated, and Degraded by Cigarette Smoke. Cigarette smoke (CS)-induced lung inflammation involves the reduction of histone deacetylase 2 (HDAC2) abundance, which is associated with steroid resistance in patients with chronic obstructive pulmonary disease and in individuals with severe asthma who smoke cigarettes. However, the molecular mechanism of CS-mediated reduction of HDAC2 is not clearly known. We hypothesized that HDAC2 is phosphorylated and subsequently degraded by the proteasome in vitro in macrophages (MonoMac6), human bronchial and primary small airway epithelial cells, and in vivo in mouse lungs in response to chronic CS exposure. Cigarette smoke extract (CSE) exposure in MonoMac6 and in bronchial and airway epithelial cells led to phosphorylation of HDAC2 on serine/threonine residues by a protein kinase CK2-mediated mechanism, decreased HDAC2 activity, and increased ubiquitin-proteasome-dependent HDAC2 degradation. CK2 and proteasome inhibitors reversed CSE-mediated HDAC2 degradation, whereas serine/threonine phosphatase inhibitor, okadaic acid, caused phosphorylation and subsequent ubiquitination of HDAC2. CS-induced HDAC2 phosphorylation was detected in mouse lungs from 2 weeks to 4 months of CS exposure, and mice showed significantly lower lung HDAC2 levels. Thus, CS-mediated down-regulation of HDAC2 in human macrophages and lung epithelial cells in vitro and in mouse lung in vivo involves the induction of serine/threonine phosphorylation and proteasomal degradation, which may have implications for steroid resistance and abnormal inflammation caused by cigarette smoke.. copd| hdac2| cigarette smoke| lung| inflammation|proinflammatory cytokine release| protein-kinase ck2| nf-kappa-b| obstructive pulmonary-disease| alveolar epithelial-cells| induced lung inflammation| oxidative stress| chromatin modification| redox regulation| degradation.	APR-2009	copd| hdac2| cigarette smoke| lung| inflammation|proinflammatory cytokine release| protein-kinase ck2| nf-kappa-b| obstructive pulmonary-disease| alveolar epithelial-cells| induced lung inflammation| oxidative stress| chromatin modification| redox regulation| degradation	Adenuga, D; Yao, H; March, TH; Seagrave, J; Rahman, I	Histone Deacetylase 2 Is Phosphorylated, Ubiquitinated, and Degraded by Cigarette Smoke		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	COPD; HDAC2; cigarette smoke; lung; inflammation	PROINFLAMMATORY CYTOKINE RELEASE; PROTEIN-KINASE CK2; NF-KAPPA-B; OBSTRUCTIVE PULMONARY-DISEASE; ALVEOLAR EPITHELIAL-CELLS; INDUCED LUNG INFLAMMATION; OXIDATIVE STRESS; CHROMATIN MODIFICATION; REDOX REGULATION; DEGRADATION	Cigarette smoke (CS)-induced lung inflammation involves the reduction of histone deacetylase 2 (HDAC2) abundance, which is associated with steroid resistance in patients with chronic obstructive pulmonary disease and in individuals with severe asthma who smoke cigarettes. However, the molecular mechanism of CS-mediated reduction of HDAC2 is not clearly known. We hypothesized that HDAC2 is phosphorylated and subsequently degraded by the proteasome in vitro in macrophages (MonoMac6), human bronchial and primary small airway epithelial cells, and in vivo in mouse lungs in response to chronic CS exposure. Cigarette smoke extract (CSE) exposure in MonoMac6 and in bronchial and airway epithelial cells led to phosphorylation of HDAC2 on serine/threonine residues by a protein kinase CK2-mediated mechanism, decreased HDAC2 activity, and increased ubiquitin-proteasome-dependent HDAC2 degradation. CK2 and proteasome inhibitors reversed CSE-mediated HDAC2 degradation, whereas serine/threonine phosphatase inhibitor, okadaic acid, caused phosphorylation and subsequent ubiquitination of HDAC2. CS-induced HDAC2 phosphorylation was detected in mouse lungs from 2 weeks to 4 months of CS exposure, and mice showed significantly lower lung HDAC2 levels. Thus, CS-mediated down-regulation of HDAC2 in human macrophages and lung epithelial cells in vitro and in mouse lung in vivo involves the induction of serine/threonine phosphorylation and proteasomal degradation, which may have implications for steroid resistance and abnormal inflammation caused by cigarette smoke.	39	106	2009	10	10.1165/rcmb.2008-0255OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Secondary prevention of coronary heart disease: Patient beliefs and health-related behaviour. Objective: Coronary heart disease (CHD) is a leading cause of illness and death in Western society. The present study was designed to evaluate the utility of illness perceptions and medication beliefs in predicting secondary preventive behaviour among patients with CHD. An extended version of Leventhal's self-regulatory model (SRM) was used as a theoretical framework for this study [Leventhal H, Nerenz DR, Steele DJ. Illness perceptions and coping with health threat. In: Baum A, Taylor SE, Singer JE, editors. Handbook of psychology and health, Volume IV: social psychological aspects of health. Hillsdale (NJ): Erlbaum,1984. pp. 21952; Home R, Weinman J. Self-regulation and self-management in asthma: exploring the role of illness perceptions and treatment beliefs in explaining non-adherence to preventer medication. Psychol Health 2002;17(l):17-32]. Method: Medical and demographic data were gathered from the medical charts of 1611 patients with established C14D from 35 randomly selected general practices. Self-report data about patients' lifestyles (diet, exercise, smoking, alcohol consumption and medication adherence) and information on illness and medication beliefs were provided from postal questionnaire (1084 patients responded; 69% response rate). The relationship between patients' beliefs and their secondary preventive behaviour was examined using regression analyses. Results: Illness perceptions appeared to be only weak predictors of smoking, exercise, diet, alcohol consumption and medication adherence, accounting for about 2% of the variance in these behaviours. Medication beliefs were moderately related to medication adherence, accounting for about 7% of the variance in scores. A strong belief in the necessity of one's medication and a lower level of concern about one's medication were associated with higher levels of adherence. Conclusions: An illness perception approach did not prove helpful in predicting secondary preventive behaviour among this group of patients. However, beliefs about medications appear to be reasonable predictive of medication adherence. (c) 2005 Elsevier Inc. All rights reserved.. coronary heart disease| health-related behaviour| illness perceptions| primary care| secondary prevention| self-regulatory model|randomized controlled-trial| chronic-fatigue-syndrome| illness perception questionnaire| myocardial-infarction| primary-care| general-practice| personal models| self-management| clinical-practice| intervention.	MAY-2005	coronary heart disease| health-related behaviour| illness perceptions| primary care| secondary prevention| self-regulatory model|randomized controlled-trial| chronic-fatigue-syndrome| illness perception questionnaire| myocardial-infarction| primary-care| general-practice| personal models| self-management| clinical-practice| intervention	Byrne, M; Walsh, J; Murphy, AW	Secondary prevention of coronary heart disease: Patient beliefs and health-related behaviour		JOURNAL OF PSYCHOSOMATIC RESEARCH	coronary heart disease; health-related behaviour; illness perceptions; primary care; secondary prevention; self-regulatory model	RANDOMIZED CONTROLLED-TRIAL; CHRONIC-FATIGUE-SYNDROME; ILLNESS PERCEPTION QUESTIONNAIRE; MYOCARDIAL-INFARCTION; PRIMARY-CARE; GENERAL-PRACTICE; PERSONAL MODELS; SELF-MANAGEMENT; CLINICAL-PRACTICE; INTERVENTION	Objective: Coronary heart disease (CHD) is a leading cause of illness and death in Western society. The present study was designed to evaluate the utility of illness perceptions and medication beliefs in predicting secondary preventive behaviour among patients with CHD. An extended version of Leventhal's self-regulatory model (SRM) was used as a theoretical framework for this study [Leventhal H, Nerenz DR, Steele DJ. Illness perceptions and coping with health threat. In: Baum A, Taylor SE, Singer JE, editors. Handbook of psychology and health, Volume IV: social psychological aspects of health. Hillsdale (NJ): Erlbaum,1984. pp. 21952; Home R, Weinman J. Self-regulation and self-management in asthma: exploring the role of illness perceptions and treatment beliefs in explaining non-adherence to preventer medication. Psychol Health 2002;17(l):17-32]. Method: Medical and demographic data were gathered from the medical charts of 1611 patients with established C14D from 35 randomly selected general practices. Self-report data about patients' lifestyles (diet, exercise, smoking, alcohol consumption and medication adherence) and information on illness and medication beliefs were provided from postal questionnaire (1084 patients responded; 69% response rate). The relationship between patients' beliefs and their secondary preventive behaviour was examined using regression analyses. Results: Illness perceptions appeared to be only weak predictors of smoking, exercise, diet, alcohol consumption and medication adherence, accounting for about 2% of the variance in these behaviours. Medication beliefs were moderately related to medication adherence, accounting for about 7% of the variance in scores. A strong belief in the necessity of one's medication and a lower level of concern about one's medication were associated with higher levels of adherence. Conclusions: An illness perception approach did not prove helpful in predicting secondary preventive behaviour among this group of patients. However, beliefs about medications appear to be reasonable predictive of medication adherence. (c) 2005 Elsevier Inc. All rights reserved.	54	106	2005	13	10.1016/j.jpsychores.2004.11.010	Psychiatry
Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure. Background: Asthma, a common and chronic disease of the airways, has a multifactorial cause involving both genetic and environmental factors. As a result, mapping genes that influence asthma susceptibility has been challenging. Objective: This study tests the hypothesis that inclusion of exposure to environmental tobacco smoke (ETS), a potential risk factor for asthma, would improve the ability to map genes for asthma. Methods: By using 144 white families from the Collaborative Study for the Genetics of Asthma, environmental information about exposure to ETS during infancy was incorporated into a genome-wide multipoint linkage analysis. Statistical significance of observed gene-environment interactions was assessed by means of simulation. Results: Three regions with nominal evidence for linkage when stratified on the basis of ETS exposure were identified (P < .01) and showed a significant increase from the baseline lod score (1p at 97 cM, D1S1669-D1S1665; 5q at 135 cM, D5S1505-D5S816; and 9q at 106 cM, D9S910; all P < .05). In addition, 2 other regions, although not meeting nominal significance after stratification on the basis of ETS exposure, showed a significant increase from baseline lod score when ETS was taken into account (1q at 240 cM, D1S549; 17p at 3 cM, D17S1308; all P < .01). Conclusion: These results illustrate how evidence for linkage of asthma can depend on exposure to an environmental factor, such as ETS. Future linkage analyses should include information on suspected environmental factors for asthma to help target new candidate susceptibility genes for asthma.. asthma| genetics| linkage| smoking| gene-environment interaction| environmental tobacco smoke| genetic epidemiology|genome-wide search| tobacco-smoke| childhood asthma| household smoking| pair linkage| risk-factors| children| chromosome-5| population| markers.	APR-2003	asthma| genetics| linkage| smoking| gene-environment interaction| environmental tobacco smoke| genetic epidemiology|genome-wide search| tobacco-smoke| childhood asthma| household smoking| pair linkage| risk-factors| children| chromosome-5| population| markers	Colilla, S; Nicolae, D; Pluzhnikov, A; Blumenthal, MN; Beaty, TH; Bleecker, ER; Lange, EM; Rich, SS; Meyers, DA; Ober, C; Cox, NJ	Evidence for gene-environment interactions in a linkage study of asthma and smoking exposure		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; genetics; linkage; smoking; gene-environment interaction; environmental tobacco smoke; genetic epidemiology	GENOME-WIDE SEARCH; TOBACCO-SMOKE; CHILDHOOD ASTHMA; HOUSEHOLD SMOKING; PAIR LINKAGE; RISK-FACTORS; CHILDREN; CHROMOSOME-5; POPULATION; MARKERS	Background: Asthma, a common and chronic disease of the airways, has a multifactorial cause involving both genetic and environmental factors. As a result, mapping genes that influence asthma susceptibility has been challenging. Objective: This study tests the hypothesis that inclusion of exposure to environmental tobacco smoke (ETS), a potential risk factor for asthma, would improve the ability to map genes for asthma. Methods: By using 144 white families from the Collaborative Study for the Genetics of Asthma, environmental information about exposure to ETS during infancy was incorporated into a genome-wide multipoint linkage analysis. Statistical significance of observed gene-environment interactions was assessed by means of simulation. Results: Three regions with nominal evidence for linkage when stratified on the basis of ETS exposure were identified (P < .01) and showed a significant increase from the baseline lod score (1p at 97 cM, D1S1669-D1S1665; 5q at 135 cM, D5S1505-D5S816; and 9q at 106 cM, D9S910; all P < .05). In addition, 2 other regions, although not meeting nominal significance after stratification on the basis of ETS exposure, showed a significant increase from baseline lod score when ETS was taken into account (1q at 240 cM, D1S549; 17p at 3 cM, D17S1308; all P < .01). Conclusion: These results illustrate how evidence for linkage of asthma can depend on exposure to an environmental factor, such as ETS. Future linkage analyses should include information on suspected environmental factors for asthma to help target new candidate susceptibility genes for asthma.	42	106	2003	7	10.1067/mai.2003.170	Allergy; Immunology
Effects of early onset asthma and in utero exposure to maternal smoking on childhood lung function. Both in utero exposures to maternal smoking and asthma are associated with chronic deficits in lung function. We hypothesized that in utero exposure affects lung function in children without asthma and synergistically affects children with early onset asthma. To investigate ate effects of in utero exposure and age at asthma diagnosis on lung function, we examined longitudinal medical history, tobacco smoke exposure, and lung function data from 5,933 participants in the Children's Health Study. We found that children exposed in utero, but without asthma, showed decreased FEV1/FVC, FEF25-75, and FEF25-75/FVC ratio. Among children without in utero exposure, early asthma diagnosis was associated. with larger decreases in FEV1, FEF25-75, and FEV1/FVC ratio compared with later diagnosed asthma. Children with in utero exposure alone and early onset asthma showed deficits in FEV1 (-13.6%; 95% confidence interval [CI], -18.9 to -8.2) and FEF25-75 (-29.7%; 95% Cl, -37.8 to -20.5) among boys; and FEF25-75 (-26.6%; 95% Cl, -36.4 to -15.1) and FEV1/FVC (-9.3%; 95% Cl, -12.9 to -5.4) among girls. The absolute differences in FEF25-75 associated with in utero exposure increased with age in children with early onset asthma. We found little evidence for effects from environmental tobacco smoke exposure alone. In summary, deficits in lung function were largest among children with in. utero exposure and early onset asthma.. asthma| children| ets| maternal smoking|environmental tobacco-smoke| southern california communities| pulmonary-function| cigarette-smoking| parental smoking| respiratory illness| differing levels| air-pollution| in-utero| children.	MAR 15-2003	asthma| children| ets| maternal smoking|environmental tobacco-smoke| southern california communities| pulmonary-function| cigarette-smoking| parental smoking| respiratory illness| differing levels| air-pollution| in-utero| children	Gilliland, FD; Berhane, K; Li, YF; Rappaport, EB; Peters, JM	Effects of early onset asthma and in utero exposure to maternal smoking on childhood lung function		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; children; ETS; maternal smoking	ENVIRONMENTAL TOBACCO-SMOKE; SOUTHERN CALIFORNIA COMMUNITIES; PULMONARY-FUNCTION; CIGARETTE-SMOKING; PARENTAL SMOKING; RESPIRATORY ILLNESS; DIFFERING LEVELS; AIR-POLLUTION; IN-UTERO; CHILDREN	Both in utero exposures to maternal smoking and asthma are associated with chronic deficits in lung function. We hypothesized that in utero exposure affects lung function in children without asthma and synergistically affects children with early onset asthma. To investigate ate effects of in utero exposure and age at asthma diagnosis on lung function, we examined longitudinal medical history, tobacco smoke exposure, and lung function data from 5,933 participants in the Children's Health Study. We found that children exposed in utero, but without asthma, showed decreased FEV1/FVC, FEF25-75, and FEF25-75/FVC ratio. Among children without in utero exposure, early asthma diagnosis was associated. with larger decreases in FEV1, FEF25-75, and FEV1/FVC ratio compared with later diagnosed asthma. Children with in utero exposure alone and early onset asthma showed deficits in FEV1 (-13.6%; 95% confidence interval [CI], -18.9 to -8.2) and FEF25-75 (-29.7%; 95% Cl, -37.8 to -20.5) among boys; and FEF25-75 (-26.6%; 95% Cl, -36.4 to -15.1) and FEV1/FVC (-9.3%; 95% Cl, -12.9 to -5.4) among girls. The absolute differences in FEF25-75 associated with in utero exposure increased with age in children with early onset asthma. We found little evidence for effects from environmental tobacco smoke exposure alone. In summary, deficits in lung function were largest among children with in. utero exposure and early onset asthma.	40	106	2003	8	10.1164/rccm.200206-616OC	General & Internal Medicine; Respiratory System
History of allergies among adults with glioma and controls. The causes of most adult gliomas are essentially unknown. Previous studies have indicated associations between immune system factors and the incidence of adult glioma, specifically that those individuals with certain allergic conditions may have decreased risk of glioma. We obtained detailed allergy histories for 405 adults newly diagnosed with glioma in the San Francisco Bay Area from 1997-1999 and 402 age-gender-ethnicity frequency-matched population-based controls. Seventy-nine percent of eligible cases or their proxies and 74% of eligible controls completed in-person interviews about allergies, age at onset, frequency, duration and severity. Overall, cases were less likely than controls to report any allergy (72% vs. 85%; odds ratio [OR] = 0.5 [0.3-0.7]); for self-reported cases (n = 269), OR = 0.7 (0.4-0.97) and for proxy-reported cases, OR = 0.3 (0.2-0.5). Pollen, dairy and nut allergies were significantly less common in cases than controls and most other allergens had odds ratios of less than one. There were no apparent trends with numbers of symptoms, route of exposure of allergen or reported severity of allergy, but there was a significant dose-response with increasing numbers of allergens (p < 0.0001 for linear trend among all cases vs. controls and p = 0.02 among self-reported cases only vs. controls). Although our work displays strong and consistent associations, future efforts must attempt to establish whether an immune system typified by proclivity to allergies, or an immunologic consequence of the allergies themselves, might be capable of preventing nascent brain tumors. The dominance of humoral immunity in the central nervous system is consistent with either of these models. Alternatively, common genetic or environmental causes for allergies and gliomagenesis may mediate or confound these observed inverse risks for allergies and gliomas, or other explanations may exist. Future work might reveal an important role for immunologic factors in gliomagenesis and potential preventative and/or therapeutic modalities. (C) 2002 Wiley-Liss, Inc.. allergy| glioma| brain cancer| case-control study|brain-tumors| medical history| risk-factors| association| asthma| interleukin-4| infection| children| cancers| sample.	APR 1-2002	allergy| glioma| brain cancer| case-control study|brain-tumors| medical history| risk-factors| association| asthma| interleukin-4| infection| children| cancers| sample	Wiemels, JL; Wiencke, JK; Sison, JD; Miike, R; McMillan, A; Wrensch, M	History of allergies among adults with glioma and controls		INTERNATIONAL JOURNAL OF CANCER	allergy; glioma; brain cancer; case-control study	BRAIN-TUMORS; MEDICAL HISTORY; RISK-FACTORS; ASSOCIATION; ASTHMA; INTERLEUKIN-4; INFECTION; CHILDREN; CANCERS; SAMPLE	The causes of most adult gliomas are essentially unknown. Previous studies have indicated associations between immune system factors and the incidence of adult glioma, specifically that those individuals with certain allergic conditions may have decreased risk of glioma. We obtained detailed allergy histories for 405 adults newly diagnosed with glioma in the San Francisco Bay Area from 1997-1999 and 402 age-gender-ethnicity frequency-matched population-based controls. Seventy-nine percent of eligible cases or their proxies and 74% of eligible controls completed in-person interviews about allergies, age at onset, frequency, duration and severity. Overall, cases were less likely than controls to report any allergy (72% vs. 85%; odds ratio [OR] = 0.5 [0.3-0.7]); for self-reported cases (n = 269), OR = 0.7 (0.4-0.97) and for proxy-reported cases, OR = 0.3 (0.2-0.5). Pollen, dairy and nut allergies were significantly less common in cases than controls and most other allergens had odds ratios of less than one. There were no apparent trends with numbers of symptoms, route of exposure of allergen or reported severity of allergy, but there was a significant dose-response with increasing numbers of allergens (p < 0.0001 for linear trend among all cases vs. controls and p = 0.02 among self-reported cases only vs. controls). Although our work displays strong and consistent associations, future efforts must attempt to establish whether an immune system typified by proclivity to allergies, or an immunologic consequence of the allergies themselves, might be capable of preventing nascent brain tumors. The dominance of humoral immunity in the central nervous system is consistent with either of these models. Alternatively, common genetic or environmental causes for allergies and gliomagenesis may mediate or confound these observed inverse risks for allergies and gliomas, or other explanations may exist. Future work might reveal an important role for immunologic factors in gliomagenesis and potential preventative and/or therapeutic modalities. (C) 2002 Wiley-Liss, Inc.	37	106	2002	7	10.1002/ijc.10239	Oncology
Decreased prevalence of sensitization to cats with high exposure to cat allergen. We investigated the relationship between current exposure to cat allergen and sensitization to cats. A questionnaire was administered and skin prick testing and home visits for collection of dust samples (Fel d 1; ELISA) were performed in 2502 adults (mean age, 31.8 years; age range, 18-58 years; 1251 women). The results for Fel d 1 in relation to sensitization to cats were analyzed for 10 deciles of cat allergen exposure (cut points [mug/g]: 0.05, 0.34, 0.48, 0.72, 1.13, 1.92, 7.2, 44, 151). The prevalence of sensitization to cat was significantly decreased in the lowest and the highest exposure groups. In the multivariate regression analysis (age, sex, socioeconomic status, and current smoking being adjusted for), the risk of sensitization to cats was significantly increased with medium exposure to Fel d 1 (3rd centile, OR 2.3, 95% CI 1.2-4.4, P = .01; 4th centile, OR 2.1, 95% CI 1.1-4.0, P = .03; 5th centile, OR 2.2, 95% CI 1.2-4.3, P = .04, 6th centile, OR 2.5, 95% CI 1.3-4.9, P = .005). These results indicate that the prevalence of sensitization to cat is decreased in the lowest and highest cat allergen exposure groups.. sensitization| asthma| allergic disease| cat| dog| dust mite| allergens| exposure|asthma| environment| children| risk.	OCT-2001	sensitization| asthma| allergic disease| cat| dog| dust mite| allergens| exposure|asthma| environment| children| risk	Custovic, A; Hallam, CL; Simpson, BM; Craven, M; Simpson, A; Woodcock, A	Decreased prevalence of sensitization to cats with high exposure to cat allergen		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	sensitization; asthma; allergic disease; cat; dog; dust mite; allergens; exposure	ASTHMA; ENVIRONMENT; CHILDREN; RISK	We investigated the relationship between current exposure to cat allergen and sensitization to cats. A questionnaire was administered and skin prick testing and home visits for collection of dust samples (Fel d 1; ELISA) were performed in 2502 adults (mean age, 31.8 years; age range, 18-58 years; 1251 women). The results for Fel d 1 in relation to sensitization to cats were analyzed for 10 deciles of cat allergen exposure (cut points [mug/g]: 0.05, 0.34, 0.48, 0.72, 1.13, 1.92, 7.2, 44, 151). The prevalence of sensitization to cat was significantly decreased in the lowest and the highest exposure groups. In the multivariate regression analysis (age, sex, socioeconomic status, and current smoking being adjusted for), the risk of sensitization to cats was significantly increased with medium exposure to Fel d 1 (3rd centile, OR 2.3, 95% CI 1.2-4.4, P = .01; 4th centile, OR 2.1, 95% CI 1.1-4.0, P = .03; 5th centile, OR 2.2, 95% CI 1.2-4.3, P = .04, 6th centile, OR 2.5, 95% CI 1.3-4.9, P = .005). These results indicate that the prevalence of sensitization to cat is decreased in the lowest and highest cat allergen exposure groups.	10	106	2001	3		Allergy; Immunology
Global Initiative for Asthma (GINA) and its objectives. Guidelines for the diagnosis and management of asthma have been available for the past 13 years and are updated regularly. However, asthma guidelines are rarely completely up-to-date because our knowledge about the pathophysiology and treatment of asthma is continually evolving. Guidelines are an increasingly familiar part of clinical practice and may have potential benefits and harms. The potential harms of guidelines can be minimized if they are rigorously developed using evidence-based medicine. Guidelines should identify key decisions and their consequences and should review the consequences of alternative decisions. In addition, guidelines should be simple, user-friendly and widely disseminated. Guidelines evolve over time and their recommendations should be supported by evidence from clinical trials. Evidence-based medicine is the new paradigm but the results and reaction to the recent meta-analysis on house-dust mite control measures highlights the need for care when incorporating such information into guidelines. Newer therapeutic agents such as the leukotriene receptor antagonists are included in the most recent revision of the GINA guidelines, but their position in asthma therapy is not yet fully established. In countries where asthma guidelines have been implemented, there appears to have been a reduction in the prevalence of moderate persistent asthma but no decrease in severe asthma. This indicates that there is still room for improvement.. asthma| guidelines| gina| corticosteroids| leukotriene receptor antagonists| prevalence|clinical guidelines.	JUN-2000	asthma| guidelines| gina| corticosteroids| leukotriene receptor antagonists| prevalence|clinical guidelines	Bousquet, J	Global Initiative for Asthma (GINA) and its objectives		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; guidelines; GINA; corticosteroids; leukotriene receptor antagonists; prevalence	CLINICAL GUIDELINES	Guidelines for the diagnosis and management of asthma have been available for the past 13 years and are updated regularly. However, asthma guidelines are rarely completely up-to-date because our knowledge about the pathophysiology and treatment of asthma is continually evolving. Guidelines are an increasingly familiar part of clinical practice and may have potential benefits and harms. The potential harms of guidelines can be minimized if they are rigorously developed using evidence-based medicine. Guidelines should identify key decisions and their consequences and should review the consequences of alternative decisions. In addition, guidelines should be simple, user-friendly and widely disseminated. Guidelines evolve over time and their recommendations should be supported by evidence from clinical trials. Evidence-based medicine is the new paradigm but the results and reaction to the recent meta-analysis on house-dust mite control measures highlights the need for care when incorporating such information into guidelines. Newer therapeutic agents such as the leukotriene receptor antagonists are included in the most recent revision of the GINA guidelines, but their position in asthma therapy is not yet fully established. In countries where asthma guidelines have been implemented, there appears to have been a reduction in the prevalence of moderate persistent asthma but no decrease in severe asthma. This indicates that there is still room for improvement.	13	106	2000	4		Allergy; Immunology
Proportional classifications of COPD phenotypes. Background: Chronic obstructive pulmonary disease (COPD) encompasses a group of disorders characterised by the presence of incompletely reversible airflow obstruction with overlapping subsets of different phenotypes including chronic bronchitis, emphysema or asthma. The aim of this study was to determine the proportion of adult subjects aged > 50 years within each phenotypic subgroup of COPD, defined as a post-bronchodilator ratio of forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) < 0.7, in accordance with current international guidelines. Methods: Adults aged > 50 years derived from a random population-based survey undertook detailed questionnaires, pulmonary function tests and chest CT scans. The proportion of subjects in each of 16 distinct phenotypes was determined based on combinations of chronic bronchitis, emphysema and asthma, with and without incompletely reversible airflow obstruction defined by a post-bronchodilator FEV(1)/FVC ratio of 0.7. Results: A total of 469 subjects completed the investigative modules, 96 of whom (20.5%) had COPD. Diagrams were constructed to demonstrate the relative proportions of the phenotypic subgroups in subjects with and without COPD. 18/96 subjects with COPD (19%) had the classical phenotypes of chronic bronchitis and/or emphysema but no asthma; asthma was the predominant COPD phenotype, being present in 53/96 (55%). When COPD was defined as a post-bronchodilator FEV(1)/FVC less than the lower limit of normal, there were one-third fewer subjects with COPD and a smaller proportion without a defined emphysema, chronic bronchitis or asthma phenotype. Conclusion: This study provides proportional classifications of the phenotypic subgroups of COPD which can be used as the basis for further research into the pathogenesis and treatment of this heterogeneous disorder.. obstructive pulmonary-disease| air-flow obstruction| lung-function| reference values| venn-diagram| risk-factors| mild asthma| follow-up| population| prevalence.	SEP-2008	obstructive pulmonary-disease| air-flow obstruction| lung-function| reference values| venn-diagram| risk-factors| mild asthma| follow-up| population| prevalence	Marsh, SE; Travers, J; Weatherall, M; Williams, MV; Aldington, S; Shirtcliffe, PM; Hansell, AL; Nowitz, MR; McNaughton, AA; Soriano, JB; Beasley, RW	Proportional classifications of COPD phenotypes		THORAX		OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; LUNG-FUNCTION; REFERENCE VALUES; VENN-DIAGRAM; RISK-FACTORS; MILD ASTHMA; FOLLOW-UP; POPULATION; PREVALENCE	Background: Chronic obstructive pulmonary disease (COPD) encompasses a group of disorders characterised by the presence of incompletely reversible airflow obstruction with overlapping subsets of different phenotypes including chronic bronchitis, emphysema or asthma. The aim of this study was to determine the proportion of adult subjects aged > 50 years within each phenotypic subgroup of COPD, defined as a post-bronchodilator ratio of forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) < 0.7, in accordance with current international guidelines. Methods: Adults aged > 50 years derived from a random population-based survey undertook detailed questionnaires, pulmonary function tests and chest CT scans. The proportion of subjects in each of 16 distinct phenotypes was determined based on combinations of chronic bronchitis, emphysema and asthma, with and without incompletely reversible airflow obstruction defined by a post-bronchodilator FEV(1)/FVC ratio of 0.7. Results: A total of 469 subjects completed the investigative modules, 96 of whom (20.5%) had COPD. Diagrams were constructed to demonstrate the relative proportions of the phenotypic subgroups in subjects with and without COPD. 18/96 subjects with COPD (19%) had the classical phenotypes of chronic bronchitis and/or emphysema but no asthma; asthma was the predominant COPD phenotype, being present in 53/96 (55%). When COPD was defined as a post-bronchodilator FEV(1)/FVC less than the lower limit of normal, there were one-third fewer subjects with COPD and a smaller proportion without a defined emphysema, chronic bronchitis or asthma phenotype. Conclusion: This study provides proportional classifications of the phenotypic subgroups of COPD which can be used as the basis for further research into the pathogenesis and treatment of this heterogeneous disorder.	44	105	2008	7	10.1136/thx.2007.089193	Respiratory System
Eosinophils: Singularly destructive effector cells or purveyors of immunoregulation?. Eosinophils are granulocytes typically associated with immune responses to a limited number of specific insults, including helminth infection and exposure to various allergens. Moreover, the overwhelming consensus from the literature is that eosinophils evolved as uniquely destructive leukocytes with cytotoxic activities as an adaptation for host defense. However, recent studies now suggest that the parochial caricature of eosinophils as effector cells with nonspecific killing abilities that evolved as a host defense mechanism against large nonphagotizable parasites is incomplete. A new paradigm has emerged describing eosinophils as initial responders to cell death/tissue damage that are a part of remodeling/repair processes and, more importantly, significant contributors to localized innate and acquired immune responses as well as systemic adaptive immunity. Significantly, this new paradigm does not preclude roles for cosinophils in host defense leading to tissue damage but instead suggests the equal importance of eosinophil-associated regulatory mechanisms modulating local tissue immune responses. The goal of this review is to summarize the data in support of this new paradigm. In turn, we believe that this expanded role provides a probable explanation for the presence of eosinophils in diverse disease settings such as asthma, allergy, cancer, transplant rejection, gastrointestinal inflammation, and viral or helminth infection.. eosinophil| immunoregulation| inflammation| innate| antigen presentation| granulocyte|smooth-muscle-cells| mast-cells| chemotactic activities| airway inflammation| lymph-nodes| t-cells| expression| il-4| antigen| asthma.	JUN-2007	eosinophil| immunoregulation| inflammation| innate| antigen presentation| granulocyte|smooth-muscle-cells| mast-cells| chemotactic activities| airway inflammation| lymph-nodes| t-cells| expression| il-4| antigen| asthma	Jacobsen, EA; Taranova, AG; Lee, NA; Lee, JJ	Eosinophils: Singularly destructive effector cells or purveyors of immunoregulation?		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	eosinophil; immunoregulation; inflammation; innate; antigen presentation; granulocyte	SMOOTH-MUSCLE-CELLS; MAST-CELLS; CHEMOTACTIC ACTIVITIES; AIRWAY INFLAMMATION; LYMPH-NODES; T-CELLS; EXPRESSION; IL-4; ANTIGEN; ASTHMA	Eosinophils are granulocytes typically associated with immune responses to a limited number of specific insults, including helminth infection and exposure to various allergens. Moreover, the overwhelming consensus from the literature is that eosinophils evolved as uniquely destructive leukocytes with cytotoxic activities as an adaptation for host defense. However, recent studies now suggest that the parochial caricature of eosinophils as effector cells with nonspecific killing abilities that evolved as a host defense mechanism against large nonphagotizable parasites is incomplete. A new paradigm has emerged describing eosinophils as initial responders to cell death/tissue damage that are a part of remodeling/repair processes and, more importantly, significant contributors to localized innate and acquired immune responses as well as systemic adaptive immunity. Significantly, this new paradigm does not preclude roles for cosinophils in host defense leading to tissue damage but instead suggests the equal importance of eosinophil-associated regulatory mechanisms modulating local tissue immune responses. The goal of this review is to summarize the data in support of this new paradigm. In turn, we believe that this expanded role provides a probable explanation for the presence of eosinophils in diverse disease settings such as asthma, allergy, cancer, transplant rejection, gastrointestinal inflammation, and viral or helminth infection.	48	105	2007	8	10.1016/j.jaci.2007.03.043	Allergy; Immunology
The National Children's Study: A 21-year prospective study of 100 000 American children. Prospective, multiyear epidemiologic studies have proven to be highly effective in discovering preventable risk factors for chronic disease. Investigations such as the Framingham Heart Study have produced blueprints for disease prevention and saved millions of lives and billions of dollars. To discover preventable environmental risk factors for disease in children, the US Congress directed the National Institute of Child Health and Human Development, through the Children's Health Act of 2000, to conduct the National Children's Study. The National Children's Study is hypothesis-driven and will seek information on environmental risks and individual susceptibility factors for asthma, birth defects, dyslexia, attention-deficit/hyperactivity disorder, autism, schizophrenia, and obesity, as well as for adverse birth outcomes. It will be conducted in a nationally representative, prospective cohort of 100 000 US-born children. Children will be followed from conception to 21 years of age. Environmental exposures (chemical, physical, biological, and psychosocial) will be assessed repeatedly during pregnancy and throughout childhood in children's homes, schools, and communities. Chemical assays will be performed by the Centers for Disease Control and Prevention, and banks of biological and environmental samples will be established for future analyses. Genetic material will be collected on each mother and child and banked to permit study of gene-environment interactions. Recruitment is scheduled to begin in 2007 at 7 Vanguard Sites and will extend to 105 sites across the United States. The National Children's Study will generate multiple satellite studies that explore methodologic issues, etiologic questions, and potential interventions. It will provide training for the next generation of researchers and practitioners in environmental pediatrics and will link to planned and ongoing prospective birth cohort studies in other nations. Data from the National Children's Study will guide development of a comprehensive blueprint for disease prevention in children.. national children's study| epidemiology| asthma| attention-deficit/hyperactivity disorder| autism| schizophrenia| obesity|coronary heart-disease| testicular dysgenesis syndrome| impaired glucose-tolerance| abdominal-wall defects| adult-blood pressure| inner-city homes| bone lead levels| physical-activity| environmental-health| risk-factors.	NOV-2006	national children's study| epidemiology| asthma| attention-deficit/hyperactivity disorder| autism| schizophrenia| obesity|coronary heart-disease| testicular dysgenesis syndrome| impaired glucose-tolerance| abdominal-wall defects| adult-blood pressure| inner-city homes| bone lead levels| physical-activity| environmental-health| risk-factors	Landrigan, PJ; Trasande, L; Thorpe, LE; Gwynn, C; Lioy, PJ; D'Alton, ME; Lipkind, HS; Swanson, J; Wadhwa, PD; Clark, EB; Rauh, VA; Perera, FP; Susser, E	The National Children's Study: A 21-year prospective study of 100 000 American children		PEDIATRICS	National Children's Study; epidemiology; asthma; attention-deficit/hyperactivity disorder; autism; schizophrenia; obesity	CORONARY HEART-DISEASE; TESTICULAR DYSGENESIS SYNDROME; IMPAIRED GLUCOSE-TOLERANCE; ABDOMINAL-WALL DEFECTS; ADULT-BLOOD PRESSURE; INNER-CITY HOMES; BONE LEAD LEVELS; PHYSICAL-ACTIVITY; ENVIRONMENTAL-HEALTH; RISK-FACTORS	Prospective, multiyear epidemiologic studies have proven to be highly effective in discovering preventable risk factors for chronic disease. Investigations such as the Framingham Heart Study have produced blueprints for disease prevention and saved millions of lives and billions of dollars. To discover preventable environmental risk factors for disease in children, the US Congress directed the National Institute of Child Health and Human Development, through the Children's Health Act of 2000, to conduct the National Children's Study. The National Children's Study is hypothesis-driven and will seek information on environmental risks and individual susceptibility factors for asthma, birth defects, dyslexia, attention-deficit/hyperactivity disorder, autism, schizophrenia, and obesity, as well as for adverse birth outcomes. It will be conducted in a nationally representative, prospective cohort of 100 000 US-born children. Children will be followed from conception to 21 years of age. Environmental exposures (chemical, physical, biological, and psychosocial) will be assessed repeatedly during pregnancy and throughout childhood in children's homes, schools, and communities. Chemical assays will be performed by the Centers for Disease Control and Prevention, and banks of biological and environmental samples will be established for future analyses. Genetic material will be collected on each mother and child and banked to permit study of gene-environment interactions. Recruitment is scheduled to begin in 2007 at 7 Vanguard Sites and will extend to 105 sites across the United States. The National Children's Study will generate multiple satellite studies that explore methodologic issues, etiologic questions, and potential interventions. It will provide training for the next generation of researchers and practitioners in environmental pediatrics and will link to planned and ongoing prospective birth cohort studies in other nations. Data from the National Children's Study will guide development of a comprehensive blueprint for disease prevention in children.	156	105	2006	14	10.1542/peds.2006-0360	Pediatrics
Which aspects of the farming lifestyle explain the inverse association with childhood allergy?. Background: Farmers' children have a reduced prevalence of allergic disorders. The specific protective environmental factors responsible are not yet identified. Objective: We sought to determine whether farmers' children in the rural county of Shropshire, England, have a reduced risk of atopy and, if so, to identify the factors responsible. Methods: The Study of Asthma and Allergy in Shropshire was a 2-stage cross-sectional study. In stage 1 a questionnaire to elicit allergic status, diet, and farming exposure was completed by the parents of 4767 children. In stage 2 a stratified subsample of 879 children underwent skin prick testing and measurement of domestic endotoxin. Results: Compared with rural nonfarming children, farmers' children had significantly less current asthma symptoms. (adjusted odds ratio (OR), 0.67; 95% CI, 0.49-0.91; P =.01) and current seasonal allergic rhinitis (adjusted OR, 0.50; 95% CI, 0.33-0.77; P =.002) but not current eczema symptoms (adjusted OR, 0.91; 95% CI, 0.68-1.21; P =.53) or atopy (adjusted OR, 0.68; 95% CI, 0.40-1.16; P =.15). In contrast, current unpasteurized milk consumption was associated with significantly less current eczema symptoms (adjusted OR, 0.59; 95% CI, 0.40-0.87; P =.008) and a greater reduction in atopy (adjusted OR, 0.24; 95% CI, 0.10-0.53; P =.001). The effect was seen in all children, independent of farming status. Unpasteurized milk consumption was associated with a 59% reduction in total IgE levels (P <.001) and higher production of whole blood stimulated IFN-gamma (P = .02). Conclusion: Unpasteurized milk consumption was the exposure mediating the protective effect on skin prick test positivity. The effect was independent of farming status and present with consumption of infrequent amounts of unpasteurized milk. Clinical implications: Unpasteurized milk might be a modifiable influence on allergic sensitization in children.. atopy| farm| unpasteurized milk| skin prick tests| children|farmers children| hay-fever| asthma| prevalence| endotoxin| limulus| milk| sensitization| exposure| diseases.	JUN-2006	atopy| farm| unpasteurized milk| skin prick tests| children|farmers children| hay-fever| asthma| prevalence| endotoxin| limulus| milk| sensitization| exposure| diseases	Perkin, MR; Strachan, DP	Which aspects of the farming lifestyle explain the inverse association with childhood allergy?		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopy; farm; unpasteurized milk; skin prick tests; children	FARMERS CHILDREN; HAY-FEVER; ASTHMA; PREVALENCE; ENDOTOXIN; LIMULUS; MILK; SENSITIZATION; EXPOSURE; DISEASES	Background: Farmers' children have a reduced prevalence of allergic disorders. The specific protective environmental factors responsible are not yet identified. Objective: We sought to determine whether farmers' children in the rural county of Shropshire, England, have a reduced risk of atopy and, if so, to identify the factors responsible. Methods: The Study of Asthma and Allergy in Shropshire was a 2-stage cross-sectional study. In stage 1 a questionnaire to elicit allergic status, diet, and farming exposure was completed by the parents of 4767 children. In stage 2 a stratified subsample of 879 children underwent skin prick testing and measurement of domestic endotoxin. Results: Compared with rural nonfarming children, farmers' children had significantly less current asthma symptoms. (adjusted odds ratio (OR), 0.67; 95% CI, 0.49-0.91; P =.01) and current seasonal allergic rhinitis (adjusted OR, 0.50; 95% CI, 0.33-0.77; P =.002) but not current eczema symptoms (adjusted OR, 0.91; 95% CI, 0.68-1.21; P =.53) or atopy (adjusted OR, 0.68; 95% CI, 0.40-1.16; P =.15). In contrast, current unpasteurized milk consumption was associated with significantly less current eczema symptoms (adjusted OR, 0.59; 95% CI, 0.40-0.87; P =.008) and a greater reduction in atopy (adjusted OR, 0.24; 95% CI, 0.10-0.53; P =.001). The effect was seen in all children, independent of farming status. Unpasteurized milk consumption was associated with a 59% reduction in total IgE levels (P <.001) and higher production of whole blood stimulated IFN-gamma (P = .02). Conclusion: Unpasteurized milk consumption was the exposure mediating the protective effect on skin prick test positivity. The effect was independent of farming status and present with consumption of infrequent amounts of unpasteurized milk. Clinical implications: Unpasteurized milk might be a modifiable influence on allergic sensitization in children.	24	105	2006	8	10.1016/j.jaci.2006.03.008	Allergy; Immunology
Nitrogen dioxide prediction in Southern California using land use regression modeling: potential for environmental health analyses. We modeled the intraurban distribution of nitrogen dioxide (NO2), a marker for traffic pollution, with land use regression, a promising new exposure classification technique. We deployed diffusion tubes to measure NO2 levels at 39 locations in the fall of 2003 in San Diego County, CA, USA. At each sample location, we constructed circular buffers in a geographic information system and captured information on roads, traffic flow, land use, population and housing. Using multiple linear regression, we were able to predict 79% of the variation in NO2 levels with four variables: traffic density within 40-300m of the sampling location, traffic density within 300-1000m, length of road within 40m and distance to the Paci. c coast. Applying this model to validation samples showed that the model predicted NO2 levels within, on average, 2.1 p.p.b for 12 training sites initially excluded from t he model. Our evaluation of this land use regression model showed that this method had excellent prediction and robustness in a North American context. These models may be useful tools in evaluating health effects of long-term exposure to traffic-related pollution.. nitrogen dioxide| traffic| land use regression| gis|particulate air-pollution| mortality| indicators| exposure| cohort| asthma.	MAR-2006	nitrogen dioxide| traffic| land use regression| gis|particulate air-pollution| mortality| indicators| exposure| cohort| asthma	Ross, Z; English, PB; Scalf, R; Gunier, R; Smorodinsky, S; Wall, S; Jerrett, M	Nitrogen dioxide prediction in Southern California using land use regression modeling: potential for environmental health analyses		JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY	nitrogen dioxide; traffic; land use regression; GIS	PARTICULATE AIR-POLLUTION; MORTALITY; INDICATORS; EXPOSURE; COHORT; ASTHMA	We modeled the intraurban distribution of nitrogen dioxide (NO2), a marker for traffic pollution, with land use regression, a promising new exposure classification technique. We deployed diffusion tubes to measure NO2 levels at 39 locations in the fall of 2003 in San Diego County, CA, USA. At each sample location, we constructed circular buffers in a geographic information system and captured information on roads, traffic flow, land use, population and housing. Using multiple linear regression, we were able to predict 79% of the variation in NO2 levels with four variables: traffic density within 40-300m of the sampling location, traffic density within 300-1000m, length of road within 40m and distance to the Paci. c coast. Applying this model to validation samples showed that the model predicted NO2 levels within, on average, 2.1 p.p.b for 12 training sites initially excluded from t he model. Our evaluation of this land use regression model showed that this method had excellent prediction and robustness in a North American context. These models may be useful tools in evaluating health effects of long-term exposure to traffic-related pollution.	18	105	2006	9	10.1038/sj.jea.7500442	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Long-term exposure to background air pollution related to respiratory and allergic health in schoolchildren. Background The impact of air pollution on asthma and allergies still remains a debate. Objective Our cross-sectional study was intended to analyse the associations between long-term exposure to background air pollution and atopic and respiratory outcomes in a large population-based sample of schoolchildren. Methods Six thousand six hundred and seventy-two children aged 9-11 years recruited from 108 randomly schools in six French cities underwent a clinical examination including a skin prick test (SPT) to common allergens, exercise-induced bronchial reactivity (EIB) and skin examination for flexural dermatitis. The prevalence of asthma, allergic rhinitis (AR) and atopic dermatitis was assessed by a standardized health questionnaire completed by the parents. Three-year-averaged concentrations of air pollutants (NO2, SO2, PM10 and O-3) were calculated at children' schools using measurements of background monitoring stations. Results After adjusting for confounders, EIB, lifetime asthma and lifetime AR were found to be positively related to an increase in the exposure to SO2, PM10 and O-3. The adjusted odds ratios (aOR) per increase of 5 mu g/m(3) of SO2 was 1.39 (95% confidence interval (CI)=1.15-1.66) for EIB and 1.19 (1.00-1.41) for lifetime asthma. The aOR for lifetime AR per increase of 10 mu g/m(3) of PM10 was 1.32 (CI=1.04-1.68). Moreover, SPT positivity was associated with O-3 (aOR=1.34; CI=1.24-1.46). Associations with past year symptoms were consistent, even if not always statistically significant. Results persisted in long-term resident (current address for at least 8 years) children. However, no consistent positive association was found with NO2. Conclusions A moderate increase in long-term exposure to background ambient air pollution was associated with an increased prevalence of respiratory and atopic indicators in children.. air pollution| allergic rhinitis| asthma| atopy| background monitoring stations| children| eczema| exercise-induced bronchial reactivity| skin prick test positivity|diesel exhaust particles| spatial variability| nitrogen-dioxide| childhood isaac| sulfur-dioxide| children| asthma| symptoms| sensitization| ozone.	OCT-2005	air pollution| allergic rhinitis| asthma| atopy| background monitoring stations| children| eczema| exercise-induced bronchial reactivity| skin prick test positivity|diesel exhaust particles| spatial variability| nitrogen-dioxide| childhood isaac| sulfur-dioxide| children| asthma| symptoms| sensitization| ozone	Penard-Morand, C; Charpin, D; Raherison, C; Kopferschmitt, C; Caillaud, D; Lavaud, F; Annesi-Maesano, I	Long-term exposure to background air pollution related to respiratory and allergic health in schoolchildren		CLINICAL AND EXPERIMENTAL ALLERGY	air pollution; allergic rhinitis; asthma; atopy; background monitoring stations; children; eczema; exercise-induced bronchial reactivity; skin prick test positivity	DIESEL EXHAUST PARTICLES; SPATIAL VARIABILITY; NITROGEN-DIOXIDE; CHILDHOOD ISAAC; SULFUR-DIOXIDE; CHILDREN; ASTHMA; SYMPTOMS; SENSITIZATION; OZONE	Background The impact of air pollution on asthma and allergies still remains a debate. Objective Our cross-sectional study was intended to analyse the associations between long-term exposure to background air pollution and atopic and respiratory outcomes in a large population-based sample of schoolchildren. Methods Six thousand six hundred and seventy-two children aged 9-11 years recruited from 108 randomly schools in six French cities underwent a clinical examination including a skin prick test (SPT) to common allergens, exercise-induced bronchial reactivity (EIB) and skin examination for flexural dermatitis. The prevalence of asthma, allergic rhinitis (AR) and atopic dermatitis was assessed by a standardized health questionnaire completed by the parents. Three-year-averaged concentrations of air pollutants (NO2, SO2, PM10 and O-3) were calculated at children' schools using measurements of background monitoring stations. Results After adjusting for confounders, EIB, lifetime asthma and lifetime AR were found to be positively related to an increase in the exposure to SO2, PM10 and O-3. The adjusted odds ratios (aOR) per increase of 5 mu g/m(3) of SO2 was 1.39 (95% confidence interval (CI)=1.15-1.66) for EIB and 1.19 (1.00-1.41) for lifetime asthma. The aOR for lifetime AR per increase of 10 mu g/m(3) of PM10 was 1.32 (CI=1.04-1.68). Moreover, SPT positivity was associated with O-3 (aOR=1.34; CI=1.24-1.46). Associations with past year symptoms were consistent, even if not always statistically significant. Results persisted in long-term resident (current address for at least 8 years) children. However, no consistent positive association was found with NO2. Conclusions A moderate increase in long-term exposure to background ambient air pollution was associated with an increased prevalence of respiratory and atopic indicators in children.	48	105	2005	9	10.1111/j.1365-2222.2005.02336.x	Allergy; Immunology
Pathogen recognition and innate immunity. Microorganisms that invade a vertebrate host are initially recognized by the innate immune system through germline-encoded pattern-recognition receptors (PRRs). Several classes of PRRs, including Toll-like receptors and cytoplasmic receptors, recognize distinct microbial components and directly activate immune cells. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.. toll-like receptors| nf-kappa-b| double-stranded-rna| plasmacytoid dendritic cells| interferon-alpha induction| ifn-beta promoter| hepatitis-c virus| signaling pathway| rig-i| antiviral response.	FEB 24-2006	toll-like receptors| nf-kappa-b| double-stranded-rna| plasmacytoid dendritic cells| interferon-alpha induction| ifn-beta promoter| hepatitis-c virus| signaling pathway| rig-i| antiviral response	Akira, S; Uematsu, S; Takeuchi, O	Pathogen recognition and innate immunity		CELL		TOLL-LIKE RECEPTORS; NF-KAPPA-B; DOUBLE-STRANDED-RNA; PLASMACYTOID DENDRITIC CELLS; INTERFERON-ALPHA INDUCTION; IFN-BETA PROMOTER; HEPATITIS-C VIRUS; SIGNALING PATHWAY; RIG-I; ANTIVIRAL RESPONSE	Microorganisms that invade a vertebrate host are initially recognized by the innate immune system through germline-encoded pattern-recognition receptors (PRRs). Several classes of PRRs, including Toll-like receptors and cytoplasmic receptors, recognize distinct microbial components and directly activate immune cells. Exposure of immune cells to the ligands of these receptors activates intracellular signaling cascades that rapidly induce the expression of a variety of overlapping and unique genes involved in the inflammatory and immune responses. New insights into innate immunity are changing the way we think about pathogenesis and the treatment of infectious diseases, allergy, and autoimmunity.	141	5045	2006	19	10.1016/j.cell.2006.02.015	Biochemistry & Molecular Biology; Cell Biology
Conversion of peripheral CD4(+)CD25(-) naive T cells to CD4(+)CD25(+) regulatory T cells by TGF-beta induction of transcription factor Foxp3. CD4(+)CD25(+) regulatory T cells (T-reg) are instrumental in the maintenance of immunological tolerance. One critical question is whether T-reg can only be generated in the thymus or can differentiate from peripheral CD4(+)CD25(-) naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4(+)CD25(-) T cells into anergic/suppressor cells that are CD25(+), CD45RB(-/low) and intracellular CTLA-4(+) can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor beta (TGF-beta). Although transcription factor Foxp3 has been shown recently to be associated with the development of T-reg, the physiological inducers for Foxp3 gene expression remain a mystery. TGF-beta induced Foxp3 gene expression in TCR-challenged CD4(+)CD25(-) naive T cells, which mediated their transition toward a regulatory T cell phenotype with potent immunosuppressive potential. These converted anergic/suppressor cells are not only unresponsive to TCR stimulation and produce neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF-beta and inhibit normal T cell proliferation in vitro. More importantly, in an ovalbumin peptide TCR transgenic adoptive transfer model, TGF-beta-converted transgenic CD4(+)CD25(+) suppressor cells proliferated in response to immunization and inhibited antigen-specific naive CD4(+) T cell expansion in vivo. Finally, in a murine asthma model, coadministration of these TGF-beta-induced suppressor T cells prevented house dust mite-induced allergic pathogenesis in lungs.. anergy| il-10| ova tcr transgenic| house dust mite| asthma|growth-factor-beta| immunological self-tolerance| antigen 4| allergic-asthma| in-vitro| disruption| ctla-4| mouse| immunosuppression| proliferation.	DEC 15-2003	anergy| il-10| ova tcr transgenic| house dust mite| asthma|growth-factor-beta| immunological self-tolerance| antigen 4| allergic-asthma| in-vitro| disruption| ctla-4| mouse| immunosuppression| proliferation	Chen, WJ; Jin, WW; Hardegen, N; Lei, KJ; Li, L; Marinos, N; McGrady, G; Wahl, SM	Conversion of peripheral CD4(+)CD25(-) naive T cells to CD4(+)CD25(+) regulatory T cells by TGF-beta induction of transcription factor Foxp3		JOURNAL OF EXPERIMENTAL MEDICINE	anergy; IL-10; OVA TCR transgenic; house dust mite; asthma	GROWTH-FACTOR-BETA; IMMUNOLOGICAL SELF-TOLERANCE; ANTIGEN 4; ALLERGIC-ASTHMA; IN-VITRO; DISRUPTION; CTLA-4; MOUSE; IMMUNOSUPPRESSION; PROLIFERATION	CD4(+)CD25(+) regulatory T cells (T-reg) are instrumental in the maintenance of immunological tolerance. One critical question is whether T-reg can only be generated in the thymus or can differentiate from peripheral CD4(+)CD25(-) naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4(+)CD25(-) T cells into anergic/suppressor cells that are CD25(+), CD45RB(-/low) and intracellular CTLA-4(+) can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor beta (TGF-beta). Although transcription factor Foxp3 has been shown recently to be associated with the development of T-reg, the physiological inducers for Foxp3 gene expression remain a mystery. TGF-beta induced Foxp3 gene expression in TCR-challenged CD4(+)CD25(-) naive T cells, which mediated their transition toward a regulatory T cell phenotype with potent immunosuppressive potential. These converted anergic/suppressor cells are not only unresponsive to TCR stimulation and produce neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF-beta and inhibit normal T cell proliferation in vitro. More importantly, in an ovalbumin peptide TCR transgenic adoptive transfer model, TGF-beta-converted transgenic CD4(+)CD25(+) suppressor cells proliferated in response to immunization and inhibited antigen-specific naive CD4(+) T cell expansion in vivo. Finally, in a murine asthma model, coadministration of these TGF-beta-induced suppressor T cells prevented house dust mite-induced allergic pathogenesis in lungs.	40	2630	2003	12	10.1084/jem.20030152	Immunology; Research & Experimental Medicine
Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.. aria| asthma| guideline| management| rhinitis|quality-of-life| house-dust-mite| aqueous nasal spray| placebo-controlled trial| skin-test reactivity| community-respiratory-health| randomized controlled-trial| intranasal fluticasone propionate| natural-rubber latex| laboratory-animal allergy.		aria| asthma| guideline| management| rhinitis|quality-of-life| house-dust-mite| aqueous nasal spray| placebo-controlled trial| skin-test reactivity| community-respiratory-health| randomized controlled-trial| intranasal fluticasone propionate| natural-rubber latex| laboratory-animal allergy	Bousquet, J; Khaltaev, N; Cruz, AA; Denburg, J; Fokkens, WJ; Togias, A; Zuberbier, T; Baena-Cagnani, CE; Canonica, GW; van Weel, C; Agache, I; Ait-Khaled, N; Bachert, C; Blaiss, MS; Bonini, S; Boulet, LP; Bousquet, PJ; Camargos, P; Carlsen, KH; Chen, Y; Custovic, A; Dahl, R; Demoly, P; Douagui, H; Durham, SR; van Wijk, RG; Kalayci, O; Kaliner, MA; Kim, YY; Kowalski, ML; Kuna, P; Le, LTT; Lemiere, C; Li, J; Lockey, RF; Mavale-Manuel, S; Meltzer, EO; Mohammad, Y; Mullol, J; Naclerio, R; Hehir, REO; Ohta, K; Ouedraogo, S; Palkonen, S; Papadopoulos, N; Passalacqua, G; Pawankar, R; Popov, TA; Rabe, KF; Rosado-Pinto, J; Scadding, GK; Simons, FER; Toskala, E; Valovirta, E; van Cauwenberge, P; Wang, DY; Wickman, M; Yawn, BP; Yorgancioglu, A; Yusuf, OM; Zar, H; Annesi-Maesano, I; Bateman, ED; Ben Kheder, A; Boakye, DA; Bouchard, J; Burney, P; Busse, WW; Chan-Yeung, M; Chavannes, NH; Chuchalin, A; Dolen, WK; Emuzyte, R; Grouse, L; Humbert, M; Jackson, C; Johnston, SL; Keith, PK; Kemp, JP; Klossek, JM; Larenas-Linnemann, D; Lipworth, B; Malo, JL; Marshall, GD; Naspitz, C; Nekam, K; Niggemann, B; Nizankowska-Mogilnicka, E; Okamoto, Y; Orru, MP; Potter, P; Price, D; Stoloff, SW; Vandenplas, O; Viegi, G; Williams, D	Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)		ALLERGY	ARIA; asthma; guideline; management; rhinitis	QUALITY-OF-LIFE; HOUSE-DUST-MITE; AQUEOUS NASAL SPRAY; PLACEBO-CONTROLLED TRIAL; SKIN-TEST REACTIVITY; COMMUNITY-RESPIRATORY-HEALTH; RANDOMIZED CONTROLLED-TRIAL; INTRANASAL FLUTICASONE PROPIONATE; NATURAL-RUBBER LATEX; LABORATORY-ANIMAL ALLERGY	Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.	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Environmental exposure to endotoxin and its relation to asthma in school-age children. Background: In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such as animal dander or tree and grass pollen. Methods: Parents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral-blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine-production profiles of peripheral-blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children. Results: Endotoxin levels in samples of dust from the child's mattress were inversely related to the occurrence of hay fever, atopic asthma, and atopic sensitization. Nonatopic wheeze was not significantly associated with the endotoxin level. Cytokine production by leukocytes (production of tumor necrosis factor (alpha), interferon-(gamma), interleukin-10, and interleukin-12) was inversely related to the endotoxin level in the bedding, indicating a marked down-regulation of immune responses in exposed children. Conclusions: A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.. house-dust endotoxin| airborne endotoxin| immune-response| childhood| life| risk| sensitization| allergy.	SEP 19-2002	house-dust endotoxin| airborne endotoxin| immune-response| childhood| life| risk| sensitization| allergy	Braun-Fahrlander, C; Riedler, J; Herz, U; Eder, W; Waser, M; Grize, L; Maisch, S; Carr, D; Gerlach, F; Bufe, A; Lauener, RP; Schierl, R; Renz, H; Nowak, D; von Mutius, E	Environmental exposure to endotoxin and its relation to asthma in school-age children		NEW ENGLAND JOURNAL OF MEDICINE		HOUSE-DUST ENDOTOXIN; AIRBORNE ENDOTOXIN; IMMUNE-RESPONSE; CHILDHOOD; LIFE; RISK; SENSITIZATION; ALLERGY	Background: In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such as animal dander or tree and grass pollen. Methods: Parents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral-blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine-production profiles of peripheral-blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children. Results: Endotoxin levels in samples of dust from the child's mattress were inversely related to the occurrence of hay fever, atopic asthma, and atopic sensitization. Nonatopic wheeze was not significantly associated with the endotoxin level. Cytokine production by leukocytes (production of tumor necrosis factor (alpha), interferon-(gamma), interleukin-10, and interleukin-12) was inversely related to the endotoxin level in the bedding, indicating a marked down-regulation of immune responses in exposed children. Conclusions: A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.	27	1064	2002	9	10.1056/NEJMoa020057	General & Internal Medicine
Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Respiratory exposure to allergen induces T cell tolerance and protection against the development of airway hyperreactivity and asthma. However, the specific mechanisms by which tolerance is induced by respiratory allergen are not clear. We report here that pulmonary dendritic cells (DCs) from mice exposed to respiratory antigen transiently produced interleukin 10 (IL-10). These phenotypically mature pulmonary DCs, which were B-7(hi) as well as producing IL-10, stimulated the development of CD4(+)T regulatory I-like cells that also produced high amounts of IL-10. In addition, adoptive transfer of pulmonary DCs from IL-10(+/+), but not IL-10(-/-), mice exposed to respiratory antigen induced antigen-specific unresponsiveness in recipient mice. These studies show that IL-10 production by DCs is critical for the induction of tolerance, and that phenotypically mature pulmonary DCs mediate tolerance induced by respiratory exposure to antigen.. colony-stimulating factor| mouse bone-marrow| cd4(+) t-cells| in-vivo| interferon-gamma| immune deviation| th2 responses| induction| differentiation| interleukin-10.	AUG-2001	colony-stimulating factor| mouse bone-marrow| cd4(+) t-cells| in-vivo| interferon-gamma| immune deviation| th2 responses| induction| differentiation| interleukin-10	Akbari, O; DeKruyff, RH; Umetsu, DT	Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen		NATURE IMMUNOLOGY		COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; CD4(+) T-CELLS; IN-VIVO; INTERFERON-GAMMA; IMMUNE DEVIATION; TH2 RESPONSES; INDUCTION; DIFFERENTIATION; INTERLEUKIN-10	Respiratory exposure to allergen induces T cell tolerance and protection against the development of airway hyperreactivity and asthma. However, the specific mechanisms by which tolerance is induced by respiratory allergen are not clear. We report here that pulmonary dendritic cells (DCs) from mice exposed to respiratory antigen transiently produced interleukin 10 (IL-10). These phenotypically mature pulmonary DCs, which were B-7(hi) as well as producing IL-10, stimulated the development of CD4(+)T regulatory I-like cells that also produced high amounts of IL-10. In addition, adoptive transfer of pulmonary DCs from IL-10(+/+), but not IL-10(-/-), mice exposed to respiratory antigen induced antigen-specific unresponsiveness in recipient mice. These studies show that IL-10 production by DCs is critical for the induction of tolerance, and that phenotypically mature pulmonary DCs mediate tolerance induced by respiratory exposure to antigen.	44	874	2001	7	10.1038/90667	Immunology
Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. Allergic asthma is an inflammatory lung disease initiated and directed by T helper cells type 2 (Th2). The mechanism involved in generation of Th2 responses to inert inhaled antigens, however, is unknown. Epidemiological evidence suggests that exposure to lipopolysaccharide (LPS) or other microbial products can influence the development and severity of asthma. However, the mechanism by which LPS influences asthma pathogenesis remains undefined. Although it is known that signaling through Toll-like receptors (TLR) is required for adaptive T helper cell type 1 (Th1) responses, it is unclear if TLRs are needed for Th2 priming. Here, we report that low level inhaled LPS signaling through TLR4 is necessary to induce Th2 responses to inhaled antigens in a mouse model of allergic sensitization. The mechanism by which LPS signaling results in Th2 sensitization involves the activation of antigen-containing dendritic cells. In contrast to low levels, inhalation of high levels of LPS with antigen results in Th1 responses. These studies suggest that the level of LPS exposure can determine the type of inflammatory response generated and provide a potential mechanistic explanation of epidemiological data on endotoxin exposure and asthma prevalence.. asthma| toll-like receptor| t cell| dendritic cell| lung|exposure| asthma| mouse| tlr4.	DEC 16-2002	asthma| toll-like receptor| t cell| dendritic cell| lung|exposure| asthma| mouse| tlr4	Eisenbarth, SC; Piggott, DA; Huleatt, JW; Visintin, I; Herrick, CA; Bottomly, K	Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen		JOURNAL OF EXPERIMENTAL MEDICINE	asthma; Toll-like receptor; T cell; dendritic cell; lung	EXPOSURE; ASTHMA; MOUSE; TLR4	Allergic asthma is an inflammatory lung disease initiated and directed by T helper cells type 2 (Th2). The mechanism involved in generation of Th2 responses to inert inhaled antigens, however, is unknown. Epidemiological evidence suggests that exposure to lipopolysaccharide (LPS) or other microbial products can influence the development and severity of asthma. However, the mechanism by which LPS influences asthma pathogenesis remains undefined. Although it is known that signaling through Toll-like receptors (TLR) is required for adaptive T helper cell type 1 (Th1) responses, it is unclear if TLRs are needed for Th2 priming. Here, we report that low level inhaled LPS signaling through TLR4 is necessary to induce Th2 responses to inhaled antigens in a mouse model of allergic sensitization. The mechanism by which LPS signaling results in Th2 sensitization involves the activation of antigen-containing dendritic cells. In contrast to low levels, inhalation of high levels of LPS with antigen results in Th1 responses. These studies suggest that the level of LPS exposure can determine the type of inflammatory response generated and provide a potential mechanistic explanation of epidemiological data on endotoxin exposure and asthma prevalence.	19	770	2002	7	10.1084/jem.20021340	Immunology; Research & Experimental Medicine
Public-health impact of outdoor and traffic-related air pollution: a European assessment. Background Air pollution contributes to mortality and morbidity. We estimated the impact of outdoor (total) and traffic-related air pollution on public health in Austria, France, and Switzerland. Attributable cases of morbidity and mortality were estimated. Methods Epidemiology-based exposure-response functions for a 10 mu g/m(3) increase in particulate matter (PM10) were used to quantify the effects of air pollution. Cases attributable to air pollution were estimated for mortality (adults greater than or equal to 30 years), respiratory and cardiovascular hospital admissions tall ages), incidence of chronic bronchitis (adults greater than or equal to 25 years), bronchitis episodes in children (<15 years), restricted activity days (adults greater than or equal to 20 years), and asthma attacks in adults and children. Population exposure (PM10) was modelled for each km(2). The traffic-related fraction was estimated based on PM10 emission inventories. Findings Air pollution caused 6% of total mortality or more than 40 000 attributable cases per year. About half of all mortality caused by air pollution was attributed to motorised traffic, accounting also for: more than 25 000 new cases of chronic bronchitis (adults); more than 290 000 episodes of bronchitis (children); more than 0.5 million asthma attacks; and more than 16 million person-days of restricted activities. Interpretation This assessment estimates the public-health impacts of current patterns of air pollution. Although individual health risks of air pollution are relatively small, the public-health consequences are considerable. Traffic-related air pollution remains a key target for public-health action in Europe. Our results, which have also been used for economic valuation, should guide decisions on the assessment of environmental health-policy options.. term ambient concentrations| respiratory health| time-series| particulate matter| nonsmoking population| inhalable particles| hospital admissions| asthmatic-children| sulfur-dioxide| united-states.	SEP 2-2000	term ambient concentrations| respiratory health| time-series| particulate matter| nonsmoking population| inhalable particles| hospital admissions| asthmatic-children| sulfur-dioxide| united-states	Kunzli, N; Kaiser, R; Medina, S; Studnicka, M; Chanel, O; Filliger, P; Herry, M; Horak, F; Puybonnieux-Texier, V; Quenel, P; Schneider, J; Seethaler, R; Vergnaud, JC; Sommer, H	Public-health impact of outdoor and traffic-related air pollution: a European assessment		LANCET		TERM AMBIENT CONCENTRATIONS; RESPIRATORY HEALTH; TIME-SERIES; PARTICULATE MATTER; NONSMOKING POPULATION; INHALABLE PARTICLES; HOSPITAL ADMISSIONS; ASTHMATIC-CHILDREN; SULFUR-DIOXIDE; UNITED-STATES	Background Air pollution contributes to mortality and morbidity. We estimated the impact of outdoor (total) and traffic-related air pollution on public health in Austria, France, and Switzerland. Attributable cases of morbidity and mortality were estimated. Methods Epidemiology-based exposure-response functions for a 10 mu g/m(3) increase in particulate matter (PM10) were used to quantify the effects of air pollution. Cases attributable to air pollution were estimated for mortality (adults greater than or equal to 30 years), respiratory and cardiovascular hospital admissions tall ages), incidence of chronic bronchitis (adults greater than or equal to 25 years), bronchitis episodes in children (<15 years), restricted activity days (adults greater than or equal to 20 years), and asthma attacks in adults and children. Population exposure (PM10) was modelled for each km(2). The traffic-related fraction was estimated based on PM10 emission inventories. Findings Air pollution caused 6% of total mortality or more than 40 000 attributable cases per year. About half of all mortality caused by air pollution was attributed to motorised traffic, accounting also for: more than 25 000 new cases of chronic bronchitis (adults); more than 290 000 episodes of bronchitis (children); more than 0.5 million asthma attacks; and more than 16 million person-days of restricted activities. Interpretation This assessment estimates the public-health impacts of current patterns of air pollution. Although individual health risks of air pollution are relatively small, the public-health consequences are considerable. Traffic-related air pollution remains a key target for public-health action in Europe. Our results, which have also been used for economic valuation, should guide decisions on the assessment of environmental health-policy options.	49	767	2000	7	10.1016/S0140-6736(00)02653-2	General & Internal Medicine
Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Background A farming environment protects against development of asthma, hay fever, and atopic sensitisation in children. We aimed to establish whether increased exposure to microbial compounds has to occur early in life to affect maturation of the immune system and thereby reduces risk for development of allergic diseases. Methods We did a cross-sectional survey in rural areas of Austria, Germany, and Switzerland. 2618 (75%) of 3504 parents of 6-13-year-old children completed a standardised questionnaire on asthma, hay fever, and atopic eczema. Children from farming families, and a random sample of non-farmers' children, who gave consent for blood samples to be obtained for measurements of specific serum IgE antibodies to common allergens were invited to participate (n = 901). Findings Exposure of children younger than 1 year, compared with those aged 1-5 years, to stables and consumption of farm milk was associated with lower frequencies of asthma (1% [3/218] vs 11% [15/138]), hay fever (3% [7] vs 13% [18]), and atopic sensitisation (12% [27] vs 29% [40]). Protection against development of asthma was independent from effect on atopic sensitisation. Continual long-term exposure to stables until age 5 years was associated with the lowest frequencies of asthma (0.8% [1/122]), hay fever (0.8% [1]), and atopic sensitisation (8.2% [10]). Interpretation Long-term and early-life exposure to stables and farm milk induces a strong protective effect against development of asthma, hay fever, and atopic sensitisation.. hay-fever| austrian children| ige production| childhood| sensitization| prevalence| atopy| risk| stimulation| challenge.	OCT 6-2001	hay-fever| austrian children| ige production| childhood| sensitization| prevalence| atopy| risk| stimulation| challenge	Riedler, J; Braun-Fahrlander, C; Eder, W; Schreuer, M; Waser, M; Maisch, S; Carr, D; Schierl, R; Nowak, D; von Mutius, E	Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey		LANCET		HAY-FEVER; AUSTRIAN CHILDREN; IGE PRODUCTION; CHILDHOOD; SENSITIZATION; PREVALENCE; ATOPY; RISK; STIMULATION; CHALLENGE	Background A farming environment protects against development of asthma, hay fever, and atopic sensitisation in children. We aimed to establish whether increased exposure to microbial compounds has to occur early in life to affect maturation of the immune system and thereby reduces risk for development of allergic diseases. Methods We did a cross-sectional survey in rural areas of Austria, Germany, and Switzerland. 2618 (75%) of 3504 parents of 6-13-year-old children completed a standardised questionnaire on asthma, hay fever, and atopic eczema. Children from farming families, and a random sample of non-farmers' children, who gave consent for blood samples to be obtained for measurements of specific serum IgE antibodies to common allergens were invited to participate (n = 901). Findings Exposure of children younger than 1 year, compared with those aged 1-5 years, to stables and consumption of farm milk was associated with lower frequencies of asthma (1% [3/218] vs 11% [15/138]), hay fever (3% [7] vs 13% [18]), and atopic sensitisation (12% [27] vs 29% [40]). Protection against development of asthma was independent from effect on atopic sensitisation. Continual long-term exposure to stables until age 5 years was associated with the lowest frequencies of asthma (0.8% [1/122]), hay fever (0.8% [1]), and atopic sensitisation (8.2% [10]). Interpretation Long-term and early-life exposure to stables and farm milk induces a strong protective effect against development of asthma, hay fever, and atopic sensitisation.	24	764	2001	5	10.1016/S0140-6736(01)06252-3	General & Internal Medicine
Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen(1-3). Its conidia production is prolific, and so human respiratory tract exposure is almost constant(4). A. fumigatus is isolated from human habitats(5) and vegetable compost heaps(6,7). In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis(8). Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.. cell-wall| saccharomyces-cerevisiae| gene-cluster| sensitization| arsenite| compost.	DEC 22-2005	cell-wall| saccharomyces-cerevisiae| gene-cluster| sensitization| arsenite| compost	Nierman, WC; Pain, A; Anderson, MJ; Wortman, JR; Kim, HS; Arroyo, J; Berriman, M; Abe, K; Archer, DB; Bermejo, C; Bennett, J; Bowyer, P; Chen, D; Collins, M; Coulsen, R; Davies, R; Dyer, PS; Farman, M; Fedorova, N; Fedorova, N; Feldblyum, TV; Fischer, R; Fosker, N; Fraser, A; Garcia, JL; Garcia, MJ; Goble, A; Goldman, GH; Gomi, K; Griffith-Jones, S; Gwilliam, R; Haas, B; Haas, H; Harris, D; Horiuchi, H; Huang, J; Humphray, S; Jimenez, J; Keller, N; Khouri, H; Kitamoto, K; Kobayashi, T; Konzack, S; Kulkarni, R; Kumagai, T; Lafton, A; Latge, JP; Li, WX; Lord, A; Majoros, WH; May, GS; Miller, BL; Mohamoud, Y; Molina, M; Monod, M; Mouyna, I; Mulligan, S; Murphy, L; O'Neil, S; Paulsen, I; Penalva, MA; Pertea, M; Price, C; Pritchard, BL; Quail, MA; Rabbinowitsch, E; Rawlins, N; Rajandream, MA; Reichard, U; Renauld, H; Robson, GD; de Cordoba, SR; Rodriguez-Pena, JM; Ronning, CM; Rutter, S; Salzberg, SL; Sanchez, M; Sanchez-Ferrero, JC; Saunders, D; Seeger, K; Squares, R; Squares, S; Takeuchi, M; Tekaia, F; Turner, G; de Aldana, CRV; Weidman, J; White, O; Woodward, J; Yu, JH; Fraser, C; Galagan, JE; Asai, K; Machida, M; Hall, N; Barrell, B; Denning, DW	Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus		NATURE		CELL-WALL; SACCHAROMYCES-CEREVISIAE; GENE-CLUSTER; SENSITIZATION; ARSENITE; COMPOST	Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen(1-3). Its conidia production is prolific, and so human respiratory tract exposure is almost constant(4). A. fumigatus is isolated from human habitats(5) and vegetable compost heaps(6,7). In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis(8). Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.	29	744	2005	6	10.1038/nature04332	Science & Technology - Other Topics
"Eosinophilic esophagitis in children and adults: A systematic review and consensus recommendations for diagnosis and treatment. During the last decade, clinical practice saw a rapid increase of patients with esophageal eosinophilia who were thought to have gastroesophageal reflux disease (GERD) but who did not respond to medical and/or surgical GERD management. Subsequent studies demonstrated that these patients had a ""new"" disease termed eosinophilic esophagitis (EE). As recognition of EE grew, so did confusion surrounding diagnostic criteria and treatment. To address these issues, a multidisciplinary task force of 31 physicians assembled with the goal of determining diagnostic criteria and making recommendations for evaluation and treatment of children and adults with suspected EE. Consensus recommendations were based upon a systematic review of the literature and expert opinion. EE is a clinicopathological disease characterized by (1) Symptoms including but not restricted to food impaction and dysphagia. in adults, and feeding intolerance and GERD symptoms in children; (2) 2 >= 15 eosinophils/HPF; (3) Exclusion of other disorders associated with similar clinical, histological, or endoscopic features, especially GERD. (Use of high dose proton pump inhibitor treatment or normal pH monitoring). Appropriate treatments include dietary approaches based upon eliminating exposure to food allergens, or topical corticosteroids. Since EE is a relatively new disease, the intent of this report is to provide current recommendations for care of affected patients and defining gaps in knowledge for future research studies.. gastroesophageal-reflux disease| atopy patch test| allergic esophagitis| ringed esophagus| skin prick| fluticasone propionate| food allergy| follow-up| endoscopic manifestation| gastrointestinal-tract."	OCT-2007	gastroesophageal-reflux disease| atopy patch test| allergic esophagitis| ringed esophagus| skin prick| fluticasone propionate| food allergy| follow-up| endoscopic manifestation| gastrointestinal-tract	Furuta, GT; Liacouras, CA; Collins, MH; Gupta, SK; Justinich, C; Putnam, PE; Bonis, P; Hassall, E; Straumann, A; Rothenberg, ME	Eosinophilic esophagitis in children and adults: A systematic review and consensus recommendations for diagnosis and treatment		GASTROENTEROLOGY		GASTROESOPHAGEAL-REFLUX DISEASE; ATOPY PATCH TEST; ALLERGIC ESOPHAGITIS; RINGED ESOPHAGUS; SKIN PRICK; FLUTICASONE PROPIONATE; FOOD ALLERGY; FOLLOW-UP; ENDOSCOPIC MANIFESTATION; GASTROINTESTINAL-TRACT	"During the last decade, clinical practice saw a rapid increase of patients with esophageal eosinophilia who were thought to have gastroesophageal reflux disease (GERD) but who did not respond to medical and/or surgical GERD management. Subsequent studies demonstrated that these patients had a ""new"" disease termed eosinophilic esophagitis (EE). As recognition of EE grew, so did confusion surrounding diagnostic criteria and treatment. To address these issues, a multidisciplinary task force of 31 physicians assembled with the goal of determining diagnostic criteria and making recommendations for evaluation and treatment of children and adults with suspected EE. Consensus recommendations were based upon a systematic review of the literature and expert opinion. EE is a clinicopathological disease characterized by (1) Symptoms including but not restricted to food impaction and dysphagia. in adults, and feeding intolerance and GERD symptoms in children; (2) 2 >= 15 eosinophils/HPF; (3) Exclusion of other disorders associated with similar clinical, histological, or endoscopic features, especially GERD. (Use of high dose proton pump inhibitor treatment or normal pH monitoring). Appropriate treatments include dietary approaches based upon eliminating exposure to food allergens, or topical corticosteroids. Since EE is a relatively new disease, the intent of this report is to provide current recommendations for care of affected patients and defining gaps in knowledge for future research studies."	121	737	2007	22	10.1053/j.gastro.2007.08.017	Gastroenterology & Hepatology
Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective. There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases. The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.. chemokine| cytokine| emphysema| macrophage| oxidative stress| protease|bronchial epithelial-cells| air-flow obstruction| bronchoalveolar lavage fluid| chronic mucus hypersecretion| randomized controlled-trial| factor-kappa-b| secretory leucoprotease inhibitor| leukocyte protease inhibitor| latent adenoviral infection| exhaled breath condensate.	OCT-2003	chemokine| cytokine| emphysema| macrophage| oxidative stress| protease|bronchial epithelial-cells| air-flow obstruction| bronchoalveolar lavage fluid| chronic mucus hypersecretion| randomized controlled-trial| factor-kappa-b| secretory leucoprotease inhibitor| leukocyte protease inhibitor| latent adenoviral infection| exhaled breath condensate	Barnes, PJ; Shapiro, SD; Pauwels, RA	Chronic obstructive pulmonary disease: molecular and cellular mechanisms		EUROPEAN RESPIRATORY JOURNAL	chemokine; cytokine; emphysema; macrophage; oxidative stress; protease	BRONCHIAL EPITHELIAL-CELLS; AIR-FLOW OBSTRUCTION; BRONCHOALVEOLAR LAVAGE FLUID; CHRONIC MUCUS HYPERSECRETION; RANDOMIZED CONTROLLED-TRIAL; FACTOR-KAPPA-B; SECRETORY LEUCOPROTEASE INHIBITOR; LEUKOCYTE PROTEASE INHIBITOR; LATENT ADENOVIRAL INFECTION; EXHALED BREATH CONDENSATE	Chronic obstructive pulmonary disease is a leading cause of death and disability, but has only recently been extensively explored from a cellular and molecular perspective. There is a chronic inflammation that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterised by increased numbers of alveolar macrophages, neutrophils and cytotoxic T-lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). A high level of oxidative stress may amplify this inflammation. There is also increased elastolysis and evidence for involvement of several elastolytic enzymes, including serine proteases, cathepsins and matrix metalloproteinases. The inflammation and proteolysis in chronic obstructive pulmonary disease is an amplification of the normal inflammatory response to cigarette smoke. This inflammation, in marked contrast to asthma, appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.	265	726	2003	17	10.1183/09031936.03.00040703	Respiratory System
Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component(1,2). To date, linkage studies have identified more than a dozen genomic regions linked to asthma(3). In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene 4 as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P=0.04-0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors(5). The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.. linkage disequilibrium| protease| proteins| markers| mutation| domain| family.	JUL 25-2002	linkage disequilibrium| protease| proteins| markers| mutation| domain| family	Van Eerdewegh, P; Little, RD; Dupuis, J; Del Mastro, RG; Falls, K; Simon, J; Torrey, D; Pandit, S; McKenny, J; Braunschweiger, K; Walsh, A; Liu, ZY; Hayward, B; Folz, C; Manning, SP; Bawa, A; Saracino, L; Thackston, M; Benchekroun, Y; Capparell, N; Wang, M; Adair, R; Feng, Y; Dubois, J; FitzGerald, MG; Huang, H; Gibson, R; Allen, KM; Pedan, A; Danzig, MR; Umland, SP; Egan, RW; Cuss, FM; Rorke, S; Clough, JB; Holloway, JW; Holgate, ST; Keith, TP	Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness		NATURE		LINKAGE DISEQUILIBRIUM; PROTEASE; PROTEINS; MARKERS; MUTATION; DOMAIN; FAMILY	Asthma is a common respiratory disorder characterized by recurrent episodes of coughing, wheezing and breathlessness. Although environmental factors such as allergen exposure are risk factors in the development of asthma, both twin and family studies point to a strong genetic component(1,2). To date, linkage studies have identified more than a dozen genomic regions linked to asthma(3). In this study, we performed a genome-wide scan on 460 Caucasian families and identified a locus on chromosome 20p13 that was linked to asthma (log(10) of the likelihood ratio (LOD), 2.94) and bronchial hyperresponsiveness (LOD, 3.93). A survey of 135 polymorphisms in 23 genes identified the ADAM33 gene 4 as being significantly associated with asthma using case-control, transmission disequilibrium and haplotype analyses (P=0.04-0.000003). ADAM proteins are membrane-anchored metalloproteases with diverse functions, which include the shedding of cell-surface proteins such as cytokines and cytokine receptors(5). The identification and characterization of ADAM33, a putative asthma susceptibility gene identified by positional cloning in an outbred population, should provide insights into the pathogenesis and natural history of this common disease.	30	710	2002	5	10.1038/nature00878	Science & Technology - Other Topics
A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. BACKGROUND: The outcome of childhood asthma in adults has been described in high-risk cohorts, but few population-based studies have reported the risk factors for persistence and relapse. METHODS: We assessed children born from April 1972 through March 1973 in Dunedin, New Zealand, repeatedly from 9 to 26 years of age with questionnaires, pulmonary-function tests, bronchial-challenge testing, and allergy testing. RESULTS: By the age of 26 years, 51.4 percent of 613 study members with complete respiratory data had reported wheezing at more than one assessment. Eighty-nine study members (14.5 percent) had wheezing that persisted from childhood to 26 years of age, whereas 168 (27.4 percent) had remission, but 76 (12.4 percent) subsequently relapsed by the age of 26. Sensitization to house dust mites predicted the persistence of wheezing (odds ratio, 2.41; P=0.001) and relapse (odds ratio, 2.18; P=0.01), as did airway hyperresponsiveness (odds ratio for persistence, 3.00; P<0.001; odds ratio for relapse, 3.03; P<0.001). Female sex predicted the persistence of wheezing (odds ratio, 1.71; P=0.03), as did smoking at the age of 21 years (odds ratio, 1.84; P=0.01). The earlier the age at onset, the greater the risk of relapse (odds ratio, 0.89 per year of increase in the age at onset; P<0.001). Pulmonary function was consistently lower in those with persistent wheezing than in those without persistent wheezing. CONCLUSIONS: In an unselected birth cohort, more than one in four children had wheezing that persisted from childhood to adulthood or that relapsed after remission. The factors predicting persistence or relapse were sensitization to house dust mites, airway hyperresponsiveness, female sex, smoking, and early age at onset. These findings, together with persistently low lung function, suggest that outcomes in adult asthma may be determined primarily in early childhood.. risk-factors| lung-function| airway hyperresponsiveness| new-zealand| wheezing illness| birth cohort| atopy| prevalence| children| life.	OCT 9-2003	risk-factors| lung-function| airway hyperresponsiveness| new-zealand| wheezing illness| birth cohort| atopy| prevalence| children| life	Sears, MR; Greene, JM; Willan, AR; Wiecek, EM; Taylor, DR; Flannery, EM; Cowan, JO; Herbison, GP; Silva, PA; Poulton, R	A longitudinal, population-based, cohort study of childhood asthma followed to adulthood		NEW ENGLAND JOURNAL OF MEDICINE		RISK-FACTORS; LUNG-FUNCTION; AIRWAY HYPERRESPONSIVENESS; NEW-ZEALAND; WHEEZING ILLNESS; BIRTH COHORT; ATOPY; PREVALENCE; CHILDREN; LIFE	BACKGROUND: The outcome of childhood asthma in adults has been described in high-risk cohorts, but few population-based studies have reported the risk factors for persistence and relapse. METHODS: We assessed children born from April 1972 through March 1973 in Dunedin, New Zealand, repeatedly from 9 to 26 years of age with questionnaires, pulmonary-function tests, bronchial-challenge testing, and allergy testing. RESULTS: By the age of 26 years, 51.4 percent of 613 study members with complete respiratory data had reported wheezing at more than one assessment. Eighty-nine study members (14.5 percent) had wheezing that persisted from childhood to 26 years of age, whereas 168 (27.4 percent) had remission, but 76 (12.4 percent) subsequently relapsed by the age of 26. Sensitization to house dust mites predicted the persistence of wheezing (odds ratio, 2.41; P=0.001) and relapse (odds ratio, 2.18; P=0.01), as did airway hyperresponsiveness (odds ratio for persistence, 3.00; P<0.001; odds ratio for relapse, 3.03; P<0.001). Female sex predicted the persistence of wheezing (odds ratio, 1.71; P=0.03), as did smoking at the age of 21 years (odds ratio, 1.84; P=0.01). The earlier the age at onset, the greater the risk of relapse (odds ratio, 0.89 per year of increase in the age at onset; P<0.001). Pulmonary function was consistently lower in those with persistent wheezing than in those without persistent wheezing. CONCLUSIONS: In an unselected birth cohort, more than one in four children had wheezing that persisted from childhood to adulthood or that relapsed after remission. The factors predicting persistence or relapse were sensitization to house dust mites, airway hyperresponsiveness, female sex, smoking, and early age at onset. These findings, together with persistently low lung function, suggest that outcomes in adult asthma may be determined primarily in early childhood.	28	672	2003	9	10.1056/NEJMoa022363	General & Internal Medicine
Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program. Rationale The Severe Asthma Research Program cohort includes subjects with persistent asthma who have undergone detailed phenotypic characterization. Previous univariate methods compared features of mild, moderate, and severe asthma. Objectives: To identify novel asthma phenotypes using an unsupervised hierarchical cluster analysis. Methods: Reduction of the initial 628 variables to 34 core variables was achieved by elimination of redundant data and transformation of categorical variables into ranked ordinal composite variables. Cluster analysis was performed on 726 subjects. Measurements and Main Results: Five groups were identified. Subjects in Cluster 1 (n = 110) have early onset atopic asthma with normal lung function treated with two or fewer controller medications (82%) and minimal health care utilization. Cluster 2 (n = 321) consists of subjects with early-onset atopic asthma and preserved lung function but increased medication requirements (29% on three or more medications) and health care utilization. Cluster 3 (n = 59) is a unique group of mostly older obese women with late-onset non-atopic asthma, moderate reductions in FEV1, and frequent oral corticosteroid use to manage exacerbations. Subjects in Clusters 4 (n = 120) and 5 (n = 116) have severe airflow obstruction with bronchodilator responsiveness but differ in to their ability to attain normal lung function, age of asthma onset, atopic status, and use of oral corticosteroids. Conclusions: Five distinct clinical phenotypes of asthma have been identified using unsupervised hierarchical cluster analysis. All clusters contain subjects who meet the American Thoracic Society definition of severe asthma, which supports clinical heterogeneity in asthma and the need for new approaches for the classification of disease severity in asthma.. asthma phenotype| definition| cluster analysis| severe asthma|exhaled nitric-oxide| randomized controlled-trial| air-flow obstruction| clinical characteristics| lung-function| obesity| adults| inflammation| children| disease.	FEB 15-2010	asthma phenotype| definition| cluster analysis| severe asthma|exhaled nitric-oxide| randomized controlled-trial| air-flow obstruction| clinical characteristics| lung-function| obesity| adults| inflammation| children| disease	Moore, WC; Meyers, DA; Wenzel, SE; Teague, WG; Li, HS; Li, XN; D'Agostino, R; Castro, M; Curran-Everett, D; Fitzpatrick, AM; Gaston, B; Jarjour, NN; Sorkness, R; Calhoun, WJ; Chung, KF; Comhair, SAA; Dweik, RA; Israel, E; Peters, SP; Busse, WW; Erzurum, SC; Bleecker, ER	Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma phenotype; definition; cluster analysis; severe asthma	EXHALED NITRIC-OXIDE; RANDOMIZED CONTROLLED-TRIAL; AIR-FLOW OBSTRUCTION; CLINICAL CHARACTERISTICS; LUNG-FUNCTION; OBESITY; ADULTS; INFLAMMATION; CHILDREN; DISEASE	Rationale The Severe Asthma Research Program cohort includes subjects with persistent asthma who have undergone detailed phenotypic characterization. Previous univariate methods compared features of mild, moderate, and severe asthma. Objectives: To identify novel asthma phenotypes using an unsupervised hierarchical cluster analysis. Methods: Reduction of the initial 628 variables to 34 core variables was achieved by elimination of redundant data and transformation of categorical variables into ranked ordinal composite variables. Cluster analysis was performed on 726 subjects. Measurements and Main Results: Five groups were identified. Subjects in Cluster 1 (n = 110) have early onset atopic asthma with normal lung function treated with two or fewer controller medications (82%) and minimal health care utilization. Cluster 2 (n = 321) consists of subjects with early-onset atopic asthma and preserved lung function but increased medication requirements (29% on three or more medications) and health care utilization. Cluster 3 (n = 59) is a unique group of mostly older obese women with late-onset non-atopic asthma, moderate reductions in FEV1, and frequent oral corticosteroid use to manage exacerbations. Subjects in Clusters 4 (n = 120) and 5 (n = 116) have severe airflow obstruction with bronchodilator responsiveness but differ in to their ability to attain normal lung function, age of asthma onset, atopic status, and use of oral corticosteroids. Conclusions: Five distinct clinical phenotypes of asthma have been identified using unsupervised hierarchical cluster analysis. All clusters contain subjects who meet the American Thoracic Society definition of severe asthma, which supports clinical heterogeneity in asthma and the need for new approaches for the classification of disease severity in asthma.	46	661	2010	9	10.1164/rccm.200906-0896OC	General & Internal Medicine; Respiratory System
The development of allergic inflammation. Allergic disorders, such as anaphylaxis, hay fever, eczema and asthma, now afflict roughly 25% of people in the developed world. In allergic subjects, persistent or repetitive exposure to allergens, which typically are intrinsically innocuous substances common in the environment, results in chronic allergic inflammation. This in turn produces long-term changes in the structure of the affected organs and substantial abnormalities in their function. It is therefore important to understand the characteristics and consequences of acute and chronic allergic inflammation, and in particular to explore how mast cells can contribute to several features of this maladaptive pattern of immunological reactivity.. obstructive pulmonary-disease| mast-cell activation| regulatory t-cells| atopic-dermatitis| hygiene hypothesis| immune-responses| epithelial-cells| bronchial-asthma| dendritic cells| nervous-system.	JUL 24-2008	obstructive pulmonary-disease| mast-cell activation| regulatory t-cells| atopic-dermatitis| hygiene hypothesis| immune-responses| epithelial-cells| bronchial-asthma| dendritic cells| nervous-system	Galli, SJ; Tsai, M; Piliponsky, AM	The development of allergic inflammation		NATURE		OBSTRUCTIVE PULMONARY-DISEASE; MAST-CELL ACTIVATION; REGULATORY T-CELLS; ATOPIC-DERMATITIS; HYGIENE HYPOTHESIS; IMMUNE-RESPONSES; EPITHELIAL-CELLS; BRONCHIAL-ASTHMA; DENDRITIC CELLS; NERVOUS-SYSTEM	Allergic disorders, such as anaphylaxis, hay fever, eczema and asthma, now afflict roughly 25% of people in the developed world. In allergic subjects, persistent or repetitive exposure to allergens, which typically are intrinsically innocuous substances common in the environment, results in chronic allergic inflammation. This in turn produces long-term changes in the structure of the affected organs and substantial abnormalities in their function. It is therefore important to understand the characteristics and consequences of acute and chronic allergic inflammation, and in particular to explore how mast cells can contribute to several features of this maladaptive pattern of immunological reactivity.	100	618	2008	10	10.1038/nature07204	Science & Technology - Other Topics
Immunology of asthma and chronic obstructive pulmonary disease. Asthma and chronic obstructive pulmonary disease (COPD) are both obstructive airway diseases that involve chronic inflammation of the respiratory tract, but the type of inflammation is markedly different between these diseases, with different patterns of inflammatory cells and mediators being involved. As described in this Review, these inflammatory profiles are largely determined by the involvement of different immune cells, which orchestrate the recruitment and activation of inflammatory cells that drive the distinct patterns of structural changes in these diseases. However, it is now becoming clear that the distinction between these diseases becomes blurred in patients with severe asthma, in asthmatic subjects who smoke and during acute exacerbations. This has important implications for the development of new therapies.. regulatory t-cells| thymic stromal lymphopoietin| air-flow limitation| peripheral airways| gene-expression| dendritic cells| induced sputum| atopic asthma| th2 cells| allergic inflammation.	MAR-2008	regulatory t-cells| thymic stromal lymphopoietin| air-flow limitation| peripheral airways| gene-expression| dendritic cells| induced sputum| atopic asthma| th2 cells| allergic inflammation	Barnes, PJ	Immunology of asthma and chronic obstructive pulmonary disease		NATURE REVIEWS IMMUNOLOGY		REGULATORY T-CELLS; THYMIC STROMAL LYMPHOPOIETIN; AIR-FLOW LIMITATION; PERIPHERAL AIRWAYS; GENE-EXPRESSION; DENDRITIC CELLS; INDUCED SPUTUM; ATOPIC ASTHMA; TH2 CELLS; ALLERGIC INFLAMMATION	Asthma and chronic obstructive pulmonary disease (COPD) are both obstructive airway diseases that involve chronic inflammation of the respiratory tract, but the type of inflammation is markedly different between these diseases, with different patterns of inflammatory cells and mediators being involved. As described in this Review, these inflammatory profiles are largely determined by the involvement of different immune cells, which orchestrate the recruitment and activation of inflammatory cells that drive the distinct patterns of structural changes in these diseases. However, it is now becoming clear that the distinction between these diseases becomes blurred in patients with severe asthma, in asthmatic subjects who smoke and during acute exacerbations. This has important implications for the development of new therapies.	122	574	2008	10	10.1038/nri2254	Immunology
Socioeconomic disparities in health: Pathways and policies. Socioeconomic status (SES) underlies three major determinants of health: health care, environmental exposure, and health behavior. In addition, chronic stress associated with lower SES may also increase morbidity and mortality. Reducing SES disparities in health will require policy initiatives addressing the components of socioeconomic status (income, education, and occupation) as well as the pathways by which these affect health, Lessons for U.S. policy approaches are taken from the Acheson Commission in England, which was charged with reducing health disparities in that country.. united-states| income-distribution| risk-factors| us adults| mortality| inequalities| insurance| disease| asthma| care.	MAR-APR-2002	united-states| income-distribution| risk-factors| us adults| mortality| inequalities| insurance| disease| asthma| care	Adler, NE; Newman, K	Socioeconomic disparities in health: Pathways and policies		HEALTH AFFAIRS		UNITED-STATES; INCOME-DISTRIBUTION; RISK-FACTORS; US ADULTS; MORTALITY; INEQUALITIES; INSURANCE; DISEASE; ASTHMA; CARE	Socioeconomic status (SES) underlies three major determinants of health: health care, environmental exposure, and health behavior. In addition, chronic stress associated with lower SES may also increase morbidity and mortality. Reducing SES disparities in health will require policy initiatives addressing the components of socioeconomic status (income, education, and occupation) as well as the pathways by which these affect health, Lessons for U.S. policy approaches are taken from the Acheson Commission in England, which was charged with reducing health disparities in that country.	79	564	2002	19	10.1377/hlthaff.21.2.60	Health Care Sciences & Services
Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Background Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay. Methods 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 &mu;g/L or <0.25 mug/L) or encouraged (greater than or equal to0.5 mug/L or greater than or equal to0.25 mug/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat. Findings Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%). Interpretation Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.. community-acquired pneumonia| obstructive pulmonary-disease| uncomplicated acute bronchitis| critically ill patients| management| therapy| exacerbations| impact| sepsis| resistance.	FEB 21-2004	community-acquired pneumonia| obstructive pulmonary-disease| uncomplicated acute bronchitis| critically ill patients| management| therapy| exacerbations| impact| sepsis| resistance	Christ-Crain, M; Jaccard-Stolz, D; Bingisser, R; Gencay, MM; Huber, PR; Tamm, M; Muller, B	Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial		LANCET		COMMUNITY-ACQUIRED PNEUMONIA; OBSTRUCTIVE PULMONARY-DISEASE; UNCOMPLICATED ACUTE BRONCHITIS; CRITICALLY ILL PATIENTS; MANAGEMENT; THERAPY; EXACERBATIONS; IMPACT; SEPSIS; RESISTANCE	Background Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay. Methods 243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 &mu;g/L or <0.25 mug/L) or encouraged (greater than or equal to0.5 mug/L or greater than or equal to0.25 mug/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat. Findings Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%). Interpretation Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications.	38	557	2004	8	10.1016/S0140-6736(04)15591-8	General & Internal Medicine
Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Asthma is caused by T-helper cell 2 (Th2)-driven immune responses, but the immunological mechanisms that protect against asthma development are poorly understood. T-cell tolerance, induced by respiratory exposure to allergen, can inhibit the development of airway hyperreactivity (AHR), a cardinal feature of asthma, and we show here that regulatory T (T-R) cells can mediate this protective effect. Mature pulmonary dendritic cells in the bronchial lymph nodes of mice exposed to respiratory allergen induced the development of TR cells, in a process that required T-cell costimulation via the inducible costimulator (ICOS)-ICOS-ligand pathway. The TR cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mice, TR cells blocked the development of AHR. Both the development and the inhibitory function of regulatory cells were dependent on the presence of IL-10 and on ICOS-ICOS-ligand interactions. These studies demonstrate that TR cells and the ICOS-ICOS-ligand signaling pathway are critically involved in respiratory tolerance and in downregulating pulmonary inflammation in asthma.. colony-stimulating factor| heat-killed listeria| mouse bone-marrow| dendritic cells| in-vivo| immune-responses| co-stimulation| molecule icos| inflammation| expression.	SEP-2002	colony-stimulating factor| heat-killed listeria| mouse bone-marrow| dendritic cells| in-vivo| immune-responses| co-stimulation| molecule icos| inflammation| expression	Akbari, O; Freeman, GJ; Meyer, EH; Greenfield, EA; Chang, TT; Sharpe, AH; Berry, G; DeKruyff, RH; Umetsu, DT	Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity		NATURE MEDICINE		COLONY-STIMULATING FACTOR; HEAT-KILLED LISTERIA; MOUSE BONE-MARROW; DENDRITIC CELLS; IN-VIVO; IMMUNE-RESPONSES; CO-STIMULATION; MOLECULE ICOS; INFLAMMATION; EXPRESSION	Asthma is caused by T-helper cell 2 (Th2)-driven immune responses, but the immunological mechanisms that protect against asthma development are poorly understood. T-cell tolerance, induced by respiratory exposure to allergen, can inhibit the development of airway hyperreactivity (AHR), a cardinal feature of asthma, and we show here that regulatory T (T-R) cells can mediate this protective effect. Mature pulmonary dendritic cells in the bronchial lymph nodes of mice exposed to respiratory allergen induced the development of TR cells, in a process that required T-cell costimulation via the inducible costimulator (ICOS)-ICOS-ligand pathway. The TR cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mice, TR cells blocked the development of AHR. Both the development and the inhibitory function of regulatory cells were dependent on the presence of IL-10 and on ICOS-ICOS-ligand interactions. These studies demonstrate that TR cells and the ICOS-ICOS-ligand signaling pathway are critically involved in respiratory tolerance and in downregulating pulmonary inflammation in asthma.	59	550	2002	9	10.1038/nm745	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Results of a home-based environmental intervention among urban children with asthma. Background: Children with asthma who live in the inner city are exposed to multiple indoor allergens and environmental tobacco smoke in their homes. Reductions in these triggers of asthma have been difficult to achieve and have seldom been associated with decreased morbidity from asthma. The objective of this study was to determine whether an environmental intervention tailored to each child's allergic sensitization and environmental risk factors could improve asthma-related outcomes. Methods: We enrolled 937 children with atopic asthma (age, 5 to 11 years) in seven major U.S. cities in a randomized, controlled trial of an environmental intervention that lasted one year (intervention year) and included education and remediation for exposure to both allergens and environmental tobacco smoke. Home environmental exposures were assessed every six months, and asthma-related complications were assessed every two months during the intervention and for one year after the intervention. Results: For every 2-week period, the intervention group had fewer days with symptoms than did the control group both during the intervention year (3.39 vs. 4.20 days, P<0.001) and the year afterward (2.62 vs. 3.21 days, P<0.001), as well as greater declines in the levels of allergens at home, such as Dermatophagoides farinae (Derf1) allergen in the bed (P<0.001) and on the bedroom floor (P=0.004), D. pteronyssinus in the bed (P=0.007), and cockroach allergen on the bedroom floor (P<0.001). Reductions in the levels of cockroach allergen and dust-mite allergen (Derf1) on the bedroom floor were significantly correlated with reduced complications of asthma (P<0.001). Conclusions: Among inner-city children with atopic asthma, an individualized, home-based, comprehensive environmental intervention decreases exposure to indoor allergens, including cockroach and dust-mite allergens, resulting in reduced asthma-associated morbidity.. house-dust-mite| inner-city children| cockroach allergen exposure| randomized controlled-trial| double-blind trial| avoidance measures| tobacco-smoke| risk-factors| low-income| reduction.	SEP 9-2004	house-dust-mite| inner-city children| cockroach allergen exposure| randomized controlled-trial| double-blind trial| avoidance measures| tobacco-smoke| risk-factors| low-income| reduction	Morgan, WJ; Crain, EF; Gruchalla, RS; O'Connor, GT; Kattan, M; Evans, RI; Stout, J; Malindzak, G; Smartt, E; Plaut, M; Walter, M; Vaughn, B; Mitchell, H	Results of a home-based environmental intervention among urban children with asthma		NEW ENGLAND JOURNAL OF MEDICINE		HOUSE-DUST-MITE; INNER-CITY CHILDREN; COCKROACH ALLERGEN EXPOSURE; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND TRIAL; AVOIDANCE MEASURES; TOBACCO-SMOKE; RISK-FACTORS; LOW-INCOME; REDUCTION	Background: Children with asthma who live in the inner city are exposed to multiple indoor allergens and environmental tobacco smoke in their homes. Reductions in these triggers of asthma have been difficult to achieve and have seldom been associated with decreased morbidity from asthma. The objective of this study was to determine whether an environmental intervention tailored to each child's allergic sensitization and environmental risk factors could improve asthma-related outcomes. Methods: We enrolled 937 children with atopic asthma (age, 5 to 11 years) in seven major U.S. cities in a randomized, controlled trial of an environmental intervention that lasted one year (intervention year) and included education and remediation for exposure to both allergens and environmental tobacco smoke. Home environmental exposures were assessed every six months, and asthma-related complications were assessed every two months during the intervention and for one year after the intervention. Results: For every 2-week period, the intervention group had fewer days with symptoms than did the control group both during the intervention year (3.39 vs. 4.20 days, P<0.001) and the year afterward (2.62 vs. 3.21 days, P<0.001), as well as greater declines in the levels of allergens at home, such as Dermatophagoides farinae (Derf1) allergen in the bed (P<0.001) and on the bedroom floor (P=0.004), D. pteronyssinus in the bed (P=0.007), and cockroach allergen on the bedroom floor (P<0.001). Reductions in the levels of cockroach allergen and dust-mite allergen (Derf1) on the bedroom floor were significantly correlated with reduced complications of asthma (P<0.001). Conclusions: Among inner-city children with atopic asthma, an individualized, home-based, comprehensive environmental intervention decreases exposure to indoor allergens, including cockroach and dust-mite allergens, resulting in reduced asthma-associated morbidity.	45	548	2004	13	10.1056/NEJMoa032097	General & Internal Medicine
Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. Background: Young children with older siblings and those who attend day care are at increased risk for infections, which in turn may protect against the development of allergic diseases, including asthma. However, the results of studies examining the relation between exposure to other children and the subsequent development of asthma have been conflicting. Methods: In a study involving 1035 children followed since birth as part of the Tucson Children's Respiratory Study, we determined the incidence of asthma (defined as at least one episode of asthma diagnosed by a physician when the child was 6 to 13 years old) and the prevalence of frequent wheezing (more than three wheezing episodes during the preceding year) in relation to the number of siblings at home and in relation to attendance at day care during infancy. Results: The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interval, 0.7 to 1.0; P = 0.04), as did attendance at day care during the first six months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2 to 1.0; P = 0.04). Children with more exposure to other children at home or at day care were more likely to have frequent wheezing at the age of 2 years than children with little or no exposure (adjusted relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.8; P = 0.01) but were less likely to have frequent wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0; P = 0.03) through the age of 13 (adjusted relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). Conclusions: Exposure of young children to older children at home or to other children at day care protects against the development of asthma and frequent wheezing later in childhood. (N Engl J Med 2000;343:538-43.) (C)2000, Massachusetts Medical Society.. respiratory-tract illness| hay-fever| 1st year| children| allergen| atopy| life| sensitization| responses| disease.	AUG 24-2000	respiratory-tract illness| hay-fever| 1st year| children| allergen| atopy| life| sensitization| responses| disease	Ball, TM; Castro-Rodriguez, JA; Griffith, KA; Holberg, CJ; Martinez, FD; Wright, AL	Siblings, day-care attendance, and the risk of asthma and wheezing during childhood		NEW ENGLAND JOURNAL OF MEDICINE		RESPIRATORY-TRACT ILLNESS; HAY-FEVER; 1ST YEAR; CHILDREN; ALLERGEN; ATOPY; LIFE; SENSITIZATION; RESPONSES; DISEASE	Background: Young children with older siblings and those who attend day care are at increased risk for infections, which in turn may protect against the development of allergic diseases, including asthma. However, the results of studies examining the relation between exposure to other children and the subsequent development of asthma have been conflicting. Methods: In a study involving 1035 children followed since birth as part of the Tucson Children's Respiratory Study, we determined the incidence of asthma (defined as at least one episode of asthma diagnosed by a physician when the child was 6 to 13 years old) and the prevalence of frequent wheezing (more than three wheezing episodes during the preceding year) in relation to the number of siblings at home and in relation to attendance at day care during infancy. Results: The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interval, 0.7 to 1.0; P = 0.04), as did attendance at day care during the first six months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2 to 1.0; P = 0.04). Children with more exposure to other children at home or at day care were more likely to have frequent wheezing at the age of 2 years than children with little or no exposure (adjusted relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.8; P = 0.01) but were less likely to have frequent wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0; P = 0.03) through the age of 13 (adjusted relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). Conclusions: Exposure of young children to older children at home or to other children at day care protects against the development of asthma and frequent wheezing later in childhood. (N Engl J Med 2000;343:538-43.) (C)2000, Massachusetts Medical Society.	35	544	2000	6	10.1056/NEJM200008243430803	General & Internal Medicine
IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. The regulation of normal and allergic immune responses to airborne allergens in the mucosa is still poorly understood, and the mechanism of specific immunotherapy (SIT) in normalizing the allergic response to such allergens is currently not clear. Accordingly, we have investigated the immunoregulatory mechanism of both normal and allergic responses to the major house-dust mite (HDM) and birch pollen allergens - Dermatophagoides pteroynyssinus (Der p)1 and Bet v 1, respectively - as well as the immunologic basis of SIT to HDM in rhinitis and asthma patients. In normal immunity to HDM and birch pollen, an allergen-specific peripheral T cell suppression to Der p 1 and Bet v 1 was observed. The deviated immune response was characterized by suppressed proliferative T cell and Th1 (IFN-gamma) and Th2 (IL-5, IL-13) cytokine responses, and increased IL-10 and TGF-beta secretion by allergen-specific T cells. Neutralization of cytokine activity showed that T cell suppression was induced by IL-10 and TGF-beta during SIT and in normal immunity to the mucosal allergens. In addition, SIT induced an antigen-specific suppressive activity in CD4(+) CD25(+) T cells of allergic individuals. Together, these results demonstrate a deviation towards a regulatory/suppressor T cell response during SIT and in normal immunity as a key event for the healthy immune response to mucosal antigens.. specific immunotherapy| t cell| il-10| tgf-beta| regulatory t cell|growth-factor-beta| grass-pollen immunotherapy| bee venom immunotherapy| human lymphocytes-t| in-vitro| helper cells| cutaneous responses| phospholipase a(2)| interferon-gamma| ige synthesis.	MAY-2003	specific immunotherapy| t cell| il-10| tgf-beta| regulatory t cell|growth-factor-beta| grass-pollen immunotherapy| bee venom immunotherapy| human lymphocytes-t| in-vitro| helper cells| cutaneous responses| phospholipase a(2)| interferon-gamma| ige synthesis	Jutel, M; Akdis, M; Budak, F; Aebischer-Casaulta, C; Wrzyszcz, M; Blaser, K; Akdis, CA	IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy		EUROPEAN JOURNAL OF IMMUNOLOGY	specific immunotherapy; T cell; IL-10; TGF-beta; regulatory T cell	GROWTH-FACTOR-BETA; GRASS-POLLEN IMMUNOTHERAPY; BEE VENOM IMMUNOTHERAPY; HUMAN LYMPHOCYTES-T; IN-VITRO; HELPER CELLS; CUTANEOUS RESPONSES; PHOSPHOLIPASE A(2); INTERFERON-GAMMA; IGE SYNTHESIS	The regulation of normal and allergic immune responses to airborne allergens in the mucosa is still poorly understood, and the mechanism of specific immunotherapy (SIT) in normalizing the allergic response to such allergens is currently not clear. Accordingly, we have investigated the immunoregulatory mechanism of both normal and allergic responses to the major house-dust mite (HDM) and birch pollen allergens - Dermatophagoides pteroynyssinus (Der p)1 and Bet v 1, respectively - as well as the immunologic basis of SIT to HDM in rhinitis and asthma patients. In normal immunity to HDM and birch pollen, an allergen-specific peripheral T cell suppression to Der p 1 and Bet v 1 was observed. The deviated immune response was characterized by suppressed proliferative T cell and Th1 (IFN-gamma) and Th2 (IL-5, IL-13) cytokine responses, and increased IL-10 and TGF-beta secretion by allergen-specific T cells. Neutralization of cytokine activity showed that T cell suppression was induced by IL-10 and TGF-beta during SIT and in normal immunity to the mucosal allergens. In addition, SIT induced an antigen-specific suppressive activity in CD4(+) CD25(+) T cells of allergic individuals. Together, these results demonstrate a deviation towards a regulatory/suppressor T cell response during SIT and in normal immunity as a key event for the healthy immune response to mucosal antigens.	57	543	2003	10	10.1002/eji.200322919	Immunology
The Danish National Birth Cohort - its background, structure and aim. Background: It is well known that the time from conception to early childhood has importance for health conditions that reach into later stages of life. Recent research supports this view,, and diseases such as cardiovascular morbidity, cancer. mental illnesses. asthma. and allergy may all have component causes that act early in life. Exposures in this period, which influence fetal growth, cell divisions, and organ functioning, may have long-lasting impact on health and disease susceptibility. Methods: To investigate these issues the Danish National Birth Cohort (Better health for mother and child) was established. A large cohort of pregnant women with long-term follow-up of the offspring was the obvious choice because many of the exposures of interest cannot be reconstructed with sufficient validity back in time. The Study needs to be large, and it is aimed to recruit 100,000 women early in pregnancy, and to continue follow-up for decades. The Nordic countries are better Suited for this kind of research than most other countries because of their population-based registers on diseases, demography md social conditions, linkable at the individual level by means of the unique ID-number given to all citizens. Exposure information is mainly collected by computer-assisted telephone interviews with the women twice during pregnancy and when their children are six and 18 months old. participants are also asked to fill in a self-administered food frequency questionnaire in mid-pregnancy. Furthermore. a biological bank has been set up with blood taken from the mother twice during pregnancy and blood from the umbilical cord taken shortly after birth. Data collection started in 1996 and the project covered all regions in Denmark in 1999. By August 2000, a total of 60,000 pregnant women had been recruited to the study. It is expected that a large number of gene-environmental hypotheses need to be based on case-control analyses within a cohort like this.. cohort| pregnancy| life-course| epidemiology|in-utero| register| exposure| childhood| health| risk| prevention| weight.	DEC-2001	cohort| pregnancy| life-course| epidemiology|in-utero| register| exposure| childhood| health| risk| prevention| weight	Olsen, J; Melbye, M; Olsen, SF; Sorensen, TIA; Aaby, P; Andersen, AMN; Taxbol, D; Hansen, KD; Juhl, M; Schow, TB; Sorensen, HT; Andresen, J; Mortensen, EL; Olesen, AW; Sondergaard, C	The Danish National Birth Cohort - its background, structure and aim		SCANDINAVIAN JOURNAL OF PUBLIC HEALTH	cohort; pregnancy; life-course; epidemiology	IN-UTERO; REGISTER; EXPOSURE; CHILDHOOD; HEALTH; RISK; PREVENTION; WEIGHT	Background: It is well known that the time from conception to early childhood has importance for health conditions that reach into later stages of life. Recent research supports this view,, and diseases such as cardiovascular morbidity, cancer. mental illnesses. asthma. and allergy may all have component causes that act early in life. Exposures in this period, which influence fetal growth, cell divisions, and organ functioning, may have long-lasting impact on health and disease susceptibility. Methods: To investigate these issues the Danish National Birth Cohort (Better health for mother and child) was established. A large cohort of pregnant women with long-term follow-up of the offspring was the obvious choice because many of the exposures of interest cannot be reconstructed with sufficient validity back in time. The Study needs to be large, and it is aimed to recruit 100,000 women early in pregnancy, and to continue follow-up for decades. The Nordic countries are better Suited for this kind of research than most other countries because of their population-based registers on diseases, demography md social conditions, linkable at the individual level by means of the unique ID-number given to all citizens. Exposure information is mainly collected by computer-assisted telephone interviews with the women twice during pregnancy and when their children are six and 18 months old. participants are also asked to fill in a self-administered food frequency questionnaire in mid-pregnancy. Furthermore. a biological bank has been set up with blood taken from the mother twice during pregnancy and blood from the umbilical cord taken shortly after birth. Data collection started in 1996 and the project covered all regions in Denmark in 1999. By August 2000, a total of 60,000 pregnant women had been recruited to the study. It is expected that a large number of gene-environmental hypotheses need to be based on case-control analyses within a cohort like this.	28	537	2001	8	10.1177/14034948010290040201	Public, Environmental & Occupational Health
Indoor air pollution in developing countries: a major environmental and public health challenge. Around 50% of people, almost all in developing countries, rely on coal and biomass in the form of wood, dung and crop residues for domestic energy. These materials are typically burnt in simple stoves with very incomplete combustion. Consequently, women and young children are exposed to high levels of indoor air pollution every clay. There is consistent evidence that indoor air pollution increases the risk of chronic obstructive pulmonary disease and of acute respiratory infections in childhood, the most important cause of death among children under 5 years of age in developing countries. Evidence also exists of associations with low birth weight, increased infant and perinatal mortality, pulmonary tuberculosis, nasopharyngeal and laryngeal cancer, cataract, and, specifically in respect of the use of coal, with lung cancer. Conflicting evidence exists with regard to asthma. All studies are observational and very few have measured exposure directly, while a substantial proportion have not dealt with confounding, As a result, risk estimates are poorly quantified and may be biased. Exposure to indoor air pollution may be responsible for nearly 2 million excess deaths in developing countries and for some 4% of the global burden of disease. Indoor air pollution is a major global public health threat requiring greatly increased efforts in the areas of research and policy-making. Research on its health effects should be strengthened, particularly in relation to tuberculosis and acute lower respiratory infections. A more systematic approach to the development and evaluation of interventions is desirable, with clearer recognition of the interrelationships between poverty and dependence on polluting fuels.. air pollution, indoor-adverse effects| fossil fuels-toxicity| lung diseases| smoke inhalation injury| cataract| developing countries|papua-new-guinea| biomass fuel combustion| lower respiratory-infections| domestic smoke pollution| different cooking fuels| young gambian children| lung-cancer mortality| wood-burning stoves| low-birth-weight| risk-factors.	2000	air pollution, indoor-adverse effects| fossil fuels-toxicity| lung diseases| smoke inhalation injury| cataract| developing countries|papua-new-guinea| biomass fuel combustion| lower respiratory-infections| domestic smoke pollution| different cooking fuels| young gambian children| lung-cancer mortality| wood-burning stoves| low-birth-weight| risk-factors	Bruce, N; Perez-Padilla, R; Albalak, R	Indoor air pollution in developing countries: a major environmental and public health challenge		BULLETIN OF THE WORLD HEALTH ORGANIZATION	air pollution, indoor-adverse effects; fossil fuels-toxicity; lung diseases; smoke inhalation injury; cataract; developing countries	PAPUA-NEW-GUINEA; BIOMASS FUEL COMBUSTION; LOWER RESPIRATORY-INFECTIONS; DOMESTIC SMOKE POLLUTION; DIFFERENT COOKING FUELS; YOUNG GAMBIAN CHILDREN; LUNG-CANCER MORTALITY; WOOD-BURNING STOVES; LOW-BIRTH-WEIGHT; RISK-FACTORS	Around 50% of people, almost all in developing countries, rely on coal and biomass in the form of wood, dung and crop residues for domestic energy. These materials are typically burnt in simple stoves with very incomplete combustion. Consequently, women and young children are exposed to high levels of indoor air pollution every clay. There is consistent evidence that indoor air pollution increases the risk of chronic obstructive pulmonary disease and of acute respiratory infections in childhood, the most important cause of death among children under 5 years of age in developing countries. Evidence also exists of associations with low birth weight, increased infant and perinatal mortality, pulmonary tuberculosis, nasopharyngeal and laryngeal cancer, cataract, and, specifically in respect of the use of coal, with lung cancer. Conflicting evidence exists with regard to asthma. All studies are observational and very few have measured exposure directly, while a substantial proportion have not dealt with confounding, As a result, risk estimates are poorly quantified and may be biased. Exposure to indoor air pollution may be responsible for nearly 2 million excess deaths in developing countries and for some 4% of the global burden of disease. Indoor air pollution is a major global public health threat requiring greatly increased efforts in the areas of research and policy-making. Research on its health effects should be strengthened, particularly in relation to tuberculosis and acute lower respiratory infections. A more systematic approach to the development and evaluation of interventions is desirable, with clearer recognition of the interrelationships between poverty and dependence on polluting fuels.	137	534	2000	15		Public, Environmental & Occupational Health
Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Background Although asthma is strongly associated with immediate hypersensitivity to indoor allergens, several studies have suggested that a cat in the house can decrease the risk of asthma. We investigated the immune response to cat and mite allergens, and asthma among children with a wide range of allergen exposure. Methods We did a population-based cross-sectional study of children (aged 12-14 years), some of whom had symptoms of asthma and bronchial hyper-reactivity, Antibodies to mite (Der f 1) and cat (Fel d 1) allergens measured by isotype (IgG and IgG4) specific radioimmunoprecipitation assays were compared with sensitisation and allergen concentrations in house dust. Findings 226 children were recruited, 47 of whom had symptoms of asthma and bronchial hyper-reactivity, Increasing exposure to mite was associated with increased prevalence of sensitisation and IgG antibody to Der f 1. By contrast, the highest exposure to cat was associated with decreased sensitisation, but a higher prevalence of IgG antibody to Fel d 1, Thus, among children with high exposure, the odds of sensitisation to mite rather than cat was 4.0 (99% CI 1.49-10.00). Furthermore. 31 of 76 children with 23 mug Fel d 1 at home, who were not sensitised to cat allergen had >125 units of IgG antibody to Fel d 1. Antibodies to Fel d 1 of the IgG4 isotype were strongly correlated with IgG antibody in both allergic and non-allergic children (r=0.84 and r=0.66, respectively). Sensitisation to mite or cat allergens was the strongest independent risk factor for asthma (p<0.001). Interpretation Exposure to cat allergen can produce an IgG and IgG4 antibody response without sensitisation or risk of asthma, This modified T-helper-2 cell response should be regarded as a form of tolerance and may be the correct objective of immunotherapy. The results may also explain the observation that animals in the house can decrease the risk of asthma.. inner-city children| risk factor| igg4 antibodies| sensitization| childhood| mite| ige| lymphocytes| reactivity| subclass.	MAR 10-2001	inner-city children| risk factor| igg4 antibodies| sensitization| childhood| mite| ige| lymphocytes| reactivity| subclass	Platts-Mills, T; Vaughan, J; Squillace, S; Woodfolk, J; Sporik, R	Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study		LANCET		INNER-CITY CHILDREN; RISK FACTOR; IGG4 ANTIBODIES; SENSITIZATION; CHILDHOOD; MITE; IGE; LYMPHOCYTES; REACTIVITY; SUBCLASS	Background Although asthma is strongly associated with immediate hypersensitivity to indoor allergens, several studies have suggested that a cat in the house can decrease the risk of asthma. We investigated the immune response to cat and mite allergens, and asthma among children with a wide range of allergen exposure. Methods We did a population-based cross-sectional study of children (aged 12-14 years), some of whom had symptoms of asthma and bronchial hyper-reactivity, Antibodies to mite (Der f 1) and cat (Fel d 1) allergens measured by isotype (IgG and IgG4) specific radioimmunoprecipitation assays were compared with sensitisation and allergen concentrations in house dust. Findings 226 children were recruited, 47 of whom had symptoms of asthma and bronchial hyper-reactivity, Increasing exposure to mite was associated with increased prevalence of sensitisation and IgG antibody to Der f 1. By contrast, the highest exposure to cat was associated with decreased sensitisation, but a higher prevalence of IgG antibody to Fel d 1, Thus, among children with high exposure, the odds of sensitisation to mite rather than cat was 4.0 (99% CI 1.49-10.00). Furthermore. 31 of 76 children with 23 mug Fel d 1 at home, who were not sensitised to cat allergen had >125 units of IgG antibody to Fel d 1. Antibodies to Fel d 1 of the IgG4 isotype were strongly correlated with IgG antibody in both allergic and non-allergic children (r=0.84 and r=0.66, respectively). Sensitisation to mite or cat allergens was the strongest independent risk factor for asthma (p<0.001). Interpretation Exposure to cat allergen can produce an IgG and IgG4 antibody response without sensitisation or risk of asthma, This modified T-helper-2 cell response should be regarded as a form of tolerance and may be the correct objective of immunotherapy. The results may also explain the observation that animals in the house can decrease the risk of asthma.	33	533	2001	5	10.1016/S0140-6736(00)04168-4	General & Internal Medicine
House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells. Barrier epithelial cells and airway dendritic cells (DCs) make up the first line of defense against inhaled substances such as house dust mite (HDM) allergen and endotoxin (lipopolysaccharide, LPS). We hypothesized that these cells need to communicate with each other to cause allergic disease. We show in irradiated chimeric mice that Toll-like receptor 4 (TLR4) expression on radioresistant lung structural cells, but not on DCs, is necessary and sufficient for DC activation in the lung and for priming of effector T helper responses to HDM. TLR4 triggering on structural cells caused production of the innate proallergic cytokines thymic stromal lymphopoietin, granulocyte-macrophage colony-stimulating factor, interleukin-25 and interleukin-33. The absence of TLR4 on structural cells, but not on hematopoietic cells, abolished HDM-driven allergic airway inflammation. Finally, inhalation of a TLR4 antagonist to target exposed epithelial cells suppressed the salient features of asthma, including bronchial hyperreactivity. Our data identify an innate immune function of airway epithelial cells that drives allergic inflammation via activation of mucosal DCs.. thymic stromal lymphopoietin| dendritic cells| epithelial-cells| alveolar macrophages| inhaled endotoxin| type-2 responses| th2 responses| lymph-nodes| t-cells| inflammation.	APR-2009	thymic stromal lymphopoietin| dendritic cells| epithelial-cells| alveolar macrophages| inhaled endotoxin| type-2 responses| th2 responses| lymph-nodes| t-cells| inflammation	Hammad, H; Chieppa, M; Perros, F; Willart, MA; Germain, RN; Lambrecht, BN	House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells		NATURE MEDICINE		THYMIC STROMAL LYMPHOPOIETIN; DENDRITIC CELLS; EPITHELIAL-CELLS; ALVEOLAR MACROPHAGES; INHALED ENDOTOXIN; TYPE-2 RESPONSES; TH2 RESPONSES; LYMPH-NODES; T-CELLS; INFLAMMATION	Barrier epithelial cells and airway dendritic cells (DCs) make up the first line of defense against inhaled substances such as house dust mite (HDM) allergen and endotoxin (lipopolysaccharide, LPS). We hypothesized that these cells need to communicate with each other to cause allergic disease. We show in irradiated chimeric mice that Toll-like receptor 4 (TLR4) expression on radioresistant lung structural cells, but not on DCs, is necessary and sufficient for DC activation in the lung and for priming of effector T helper responses to HDM. TLR4 triggering on structural cells caused production of the innate proallergic cytokines thymic stromal lymphopoietin, granulocyte-macrophage colony-stimulating factor, interleukin-25 and interleukin-33. The absence of TLR4 on structural cells, but not on hematopoietic cells, abolished HDM-driven allergic airway inflammation. Finally, inhalation of a TLR4 antagonist to target exposed epithelial cells suppressed the salient features of asthma, including bronchial hyperreactivity. Our data identify an innate immune function of airway epithelial cells that drives allergic inflammation via activation of mucosal DCs.	45	522	2009	7	10.1038/nm.1946	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Bioaerosol health effects and exposure assessment: Progress and prospects. Exposures to bioaerosols in the occupational environment are associated with a wide range of health effects with major public health impact, including infectious diseases, acute toxic effects, allergies and cancer. Respiratory symptoms and lung function impairment are the most widely studied and probably among the most important bioaerosol-associated health effects. In addition to these adverse health effects some protective effects of microbial exposure on atopy and atopic conditions has also been suggested. New industrial activities have emerged in recent years in which exposures to bioaerosols can be abundant, e.g. the waste recycling and composting industry, biotechnology industries producing highly purified enzymes and the detergent and food industries that make use of these enzymes. Dose-response relationships have not been established for most biological agents and knowledge about threshold values is sparse. Exposure limits are available for some contaminants, e.g. wood dust, subtilisins (bacterial enzymes) and flour dust. Exposure limits for bacterial endotoxin have been proposed. Risk assessment is seriously hampered by the lack of valid quantitative exposure assessment methods. Traditional culture methods to quantify microbial exposures have proven to be of limited use. Non-culture methods and assessment methods for microbial constituents [e.g. allergens, endotoxin, beta(1-->3)-glucans, fungal extracellular polysaccharides] appear more successful; however, experience with these methods is generally limited. Therefore, more research is needed to establish better exposure assessment tools and validate newly developed methods. Other important areas that require further research include: potential protective effects of microbial exposures on atopy and atopic diseases, inter-individual susceptibility for biological exposures, interactions of bioaerosols with non-biological agents and other potential health effects such as skin and neurological conditions and birth effects.. asthma| beta(1,3)-glucans| bioaerosols| cancer| endotoxin| exposure assessment| infections| microorganisms|upper airway inflammation| work-related symptoms| house-dust endotoxin| legionnaires-disease| inhaled endotoxin| cotton dust| grain dust| hypersensitivity pneumonitis| environmental exposure| response relationships.	APR-2003	asthma| beta(1,3)-glucans| bioaerosols| cancer| endotoxin| exposure assessment| infections| microorganisms|upper airway inflammation| work-related symptoms| house-dust endotoxin| legionnaires-disease| inhaled endotoxin| cotton dust| grain dust| hypersensitivity pneumonitis| environmental exposure| response relationships	Douwes, J; Thorne, P; Pearce, N; Heederik, D	Bioaerosol health effects and exposure assessment: Progress and prospects		ANNALS OF OCCUPATIONAL HYGIENE	asthma; beta(1,3)-glucans; bioaerosols; cancer; endotoxin; exposure assessment; infections; microorganisms	UPPER AIRWAY INFLAMMATION; WORK-RELATED SYMPTOMS; HOUSE-DUST ENDOTOXIN; LEGIONNAIRES-DISEASE; INHALED ENDOTOXIN; COTTON DUST; GRAIN DUST; HYPERSENSITIVITY PNEUMONITIS; ENVIRONMENTAL EXPOSURE; RESPONSE RELATIONSHIPS	Exposures to bioaerosols in the occupational environment are associated with a wide range of health effects with major public health impact, including infectious diseases, acute toxic effects, allergies and cancer. Respiratory symptoms and lung function impairment are the most widely studied and probably among the most important bioaerosol-associated health effects. In addition to these adverse health effects some protective effects of microbial exposure on atopy and atopic conditions has also been suggested. New industrial activities have emerged in recent years in which exposures to bioaerosols can be abundant, e.g. the waste recycling and composting industry, biotechnology industries producing highly purified enzymes and the detergent and food industries that make use of these enzymes. Dose-response relationships have not been established for most biological agents and knowledge about threshold values is sparse. Exposure limits are available for some contaminants, e.g. wood dust, subtilisins (bacterial enzymes) and flour dust. Exposure limits for bacterial endotoxin have been proposed. Risk assessment is seriously hampered by the lack of valid quantitative exposure assessment methods. Traditional culture methods to quantify microbial exposures have proven to be of limited use. Non-culture methods and assessment methods for microbial constituents [e.g. allergens, endotoxin, beta(1-->3)-glucans, fungal extracellular polysaccharides] appear more successful; however, experience with these methods is generally limited. Therefore, more research is needed to establish better exposure assessment tools and validate newly developed methods. Other important areas that require further research include: potential protective effects of microbial exposures on atopy and atopic diseases, inter-individual susceptibility for biological exposures, interactions of bioaerosols with non-biological agents and other potential health effects such as skin and neurological conditions and birth effects.	154	509	2003	14	10.1093/annhyg/meg032	Public, Environmental & Occupational Health; Toxicology
Nitric oxide in health and disease of the respiratory system. During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation Of L-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. The concentration of this molecule in exhaled air is abnormal in activated states of different inflammatory airway diseases, and its monitoring is potentially a major advance in the management of, e.g., asthma. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response. The fundamental mechanisms driving the altered NO bioactivity under pathological conditions still need to be fully clarified, because their regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways.. airway smooth-muscle| obstructive pulmonary-disease| guinea-pig trachea| vasoactive-intestinal-peptide| synthase gene-expression| bronchial epithelial-cells| human alveolar macrophages| primary ciliary dyskinesia| nucleus-tractus-solitarii| early asthmatic reaction.	JUL-2004	airway smooth-muscle| obstructive pulmonary-disease| guinea-pig trachea| vasoactive-intestinal-peptide| synthase gene-expression| bronchial epithelial-cells| human alveolar macrophages| primary ciliary dyskinesia| nucleus-tractus-solitarii| early asthmatic reaction	Ricciardolo, FLM; Sterk, PJ; Gaston, B; Folkerts, G	Nitric oxide in health and disease of the respiratory system		PHYSIOLOGICAL REVIEWS		AIRWAY SMOOTH-MUSCLE; OBSTRUCTIVE PULMONARY-DISEASE; GUINEA-PIG TRACHEA; VASOACTIVE-INTESTINAL-PEPTIDE; SYNTHASE GENE-EXPRESSION; BRONCHIAL EPITHELIAL-CELLS; HUMAN ALVEOLAR MACROPHAGES; PRIMARY CILIARY DYSKINESIA; NUCLEUS-TRACTUS-SOLITARII; EARLY ASTHMATIC REACTION	During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation Of L-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. The concentration of this molecule in exhaled air is abnormal in activated states of different inflammatory airway diseases, and its monitoring is potentially a major advance in the management of, e.g., asthma. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response. The fundamental mechanisms driving the altered NO bioactivity under pathological conditions still need to be fully clarified, because their regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways.	471	487	2004	35	10.1152/physrev.00034.2003	Physiology
A mechanism for the initiation of allergen-induced T helper type 2 responses. Both metazoan parasites and simple protein allergens induce T helper type 2 (T(H)2) immune responses, but the mechanisms by which the innate immune system senses these stimuli are unknown. In addition, the cellular source of cytokines that control T(H)2 differentiation in vivo has not been defined. Here we showed that basophils were activated and recruited to the draining lymph nodes specifically in response to T(H)2-inducing allergen challenge. Furthermore, we demonstrate that the basophil was the accessory cell type required for T(H)2 induction in response to protease allergens. Finally, we show that basophils were directly activated by protease allergens and produced T(H)2-inducing cytokines, including interleukin 4 and thymic stromal lymphopoietin, which are involved in T(H)2 differentiation in vivo.. thymic stromal lymphopoietin| dust-mite allergen| mast-cells| th2 differentiation| cytokine production| nematode parasites| dendritic cells| il-4 expression| lymph-nodes| in-vivo.	MAR-2008	thymic stromal lymphopoietin| dust-mite allergen| mast-cells| th2 differentiation| cytokine production| nematode parasites| dendritic cells| il-4 expression| lymph-nodes| in-vivo	Sokol, CL; Barton, GM; Farr, AG; Medzhitov, R	A mechanism for the initiation of allergen-induced T helper type 2 responses		NATURE IMMUNOLOGY		THYMIC STROMAL LYMPHOPOIETIN; DUST-MITE ALLERGEN; MAST-CELLS; TH2 DIFFERENTIATION; CYTOKINE PRODUCTION; NEMATODE PARASITES; DENDRITIC CELLS; IL-4 EXPRESSION; LYMPH-NODES; IN-VIVO	Both metazoan parasites and simple protein allergens induce T helper type 2 (T(H)2) immune responses, but the mechanisms by which the innate immune system senses these stimuli are unknown. In addition, the cellular source of cytokines that control T(H)2 differentiation in vivo has not been defined. Here we showed that basophils were activated and recruited to the draining lymph nodes specifically in response to T(H)2-inducing allergen challenge. Furthermore, we demonstrate that the basophil was the accessory cell type required for T(H)2 induction in response to protease allergens. Finally, we show that basophils were directly activated by protease allergens and produced T(H)2-inducing cytokines, including interleukin 4 and thymic stromal lymphopoietin, which are involved in T(H)2 differentiation in vivo.	49	486	2008	9	10.1038/ni1558	Immunology
Probiotics in the management of atopic eczema. Background Over the last two decades the incidence of allergic diseases has increased in industrialized countries, and consequently new approaches have to be explored. Objective The potential of probiotics to control allergic inflammation at an early age was assessed in a randomized double-blind placebo-controlled study. Methods A total of 27 infants, mean age 4.6 months, who manifested atopic eczema during exclusive breast-feeding and who have had no exposure to any infant or substitute formula were weaned to probiotic-supplemented. Bifidobacterium lactis Bb-12 or Lactobacillus strain GG (ATCC 53103), extensively hydrolysed whey formulas or to the same formula without probiotics. The extent and severity of atopic eczema, the growth and nutrition of infants, and concentrations of circulating cytokines/chemokines and soluble cell surface adhesion molecules in serum and methyl-histamine and eosinophilic protein X in urine were determined. Results The SCORAD score reflecting the extent and severity of atopic eczema was 16 (7-25) during breast-feeding, median (interquartile range). After 2 months, a significant improvement in skin condition occurred in patients given probiotic-supplemented formulas, as compared to the unsupplemented group; chi (2) = 12.27, P = 0.002. SCORAD decreased in the Bifidobacterium lactis Bb-12 group to 0 (0-3.8), and in the Lactobacillus GG group to 1 (0.1-8.7), vs unsupplemented 13.4 (4.5-18.2), median (interquartile range), in parallel with a reduction in the concentration of soluble CD4 in serum and eosinophilic protein X in urine. Conclusion The results provide the first clinical demonstration of specific probiotic strains modifying the changes related to allergic inflammation. The data further indicate that probiotics may counteract inflammatory responses beyond the intestinal milieu. The combined effects of these probiotic strains will guide infants through the weaning period, when sensitization to newly encountered antigens is initiated. The probiotic approach may thus offer a new direction in the search for future foods for allergy treatment and prevention strategies.. allergic inflammation| atopy| breast-feeding| food allergy| infants| probiotics|gg-derived enzymes| asthma| infants| proliferation| dermatitis| infection| disorders| responses| children| diarrhea.	NOV-2000	allergic inflammation| atopy| breast-feeding| food allergy| infants| probiotics|gg-derived enzymes| asthma| infants| proliferation| dermatitis| infection| disorders| responses| children| diarrhea	Isolauri, E; Arvola, T; Sutas, Y; Moilanen, E; Salminen, S	Probiotics in the management of atopic eczema		CLINICAL AND EXPERIMENTAL ALLERGY	allergic inflammation; atopy; breast-feeding; food allergy; infants; probiotics	GG-DERIVED ENZYMES; ASTHMA; INFANTS; PROLIFERATION; DERMATITIS; INFECTION; DISORDERS; RESPONSES; CHILDREN; DIARRHEA	Background Over the last two decades the incidence of allergic diseases has increased in industrialized countries, and consequently new approaches have to be explored. Objective The potential of probiotics to control allergic inflammation at an early age was assessed in a randomized double-blind placebo-controlled study. Methods A total of 27 infants, mean age 4.6 months, who manifested atopic eczema during exclusive breast-feeding and who have had no exposure to any infant or substitute formula were weaned to probiotic-supplemented. Bifidobacterium lactis Bb-12 or Lactobacillus strain GG (ATCC 53103), extensively hydrolysed whey formulas or to the same formula without probiotics. The extent and severity of atopic eczema, the growth and nutrition of infants, and concentrations of circulating cytokines/chemokines and soluble cell surface adhesion molecules in serum and methyl-histamine and eosinophilic protein X in urine were determined. Results The SCORAD score reflecting the extent and severity of atopic eczema was 16 (7-25) during breast-feeding, median (interquartile range). After 2 months, a significant improvement in skin condition occurred in patients given probiotic-supplemented formulas, as compared to the unsupplemented group; chi (2) = 12.27, P = 0.002. SCORAD decreased in the Bifidobacterium lactis Bb-12 group to 0 (0-3.8), and in the Lactobacillus GG group to 1 (0.1-8.7), vs unsupplemented 13.4 (4.5-18.2), median (interquartile range), in parallel with a reduction in the concentration of soluble CD4 in serum and eosinophilic protein X in urine. Conclusion The results provide the first clinical demonstration of specific probiotic strains modifying the changes related to allergic inflammation. The data further indicate that probiotics may counteract inflammatory responses beyond the intestinal milieu. The combined effects of these probiotic strains will guide infants through the weaning period, when sensitization to newly encountered antigens is initiated. The probiotic approach may thus offer a new direction in the search for future foods for allergy treatment and prevention strategies.	39	479	2000	7		Allergy; Immunology
Immunoregulatory functions of surfactant proteins. Because the lungs function as the body's gas-exchange organ, they are inevitably exposed to air that is contaminated with pathogens, allergens and pollutants. Host-defence mechanisms within the lungs must facilitate clearance of inhaled pathogens and particles while minimizing an inflammatory response that could damage the thin, delicate gas-exchanging epithelium. Pulmonary surfactant is a complex of lipids and proteins that enhances pathogen clearance and regulates adaptive and innate immune-cell functions. In this article, I review the structure and functions of the surfactant proteins SP-A and SP-D in regulating host immune defence and in modulating inflammatory responses.. respiratory syncytial virus| influenza-a viruses| pulmonary host-defense| proinflammatory cytokine production| carbohydrate-recognition domain| human alveolar macrophages| bacillus-calmette-guerin| airway dendritic cells| gram-negative bacteria| mannose-binding lectin.	JAN-2005	respiratory syncytial virus| influenza-a viruses| pulmonary host-defense| proinflammatory cytokine production| carbohydrate-recognition domain| human alveolar macrophages| bacillus-calmette-guerin| airway dendritic cells| gram-negative bacteria| mannose-binding lectin	Wright, JR	Immunoregulatory functions of surfactant proteins		NATURE REVIEWS IMMUNOLOGY		RESPIRATORY SYNCYTIAL VIRUS; INFLUENZA-A VIRUSES; PULMONARY HOST-DEFENSE; PROINFLAMMATORY CYTOKINE PRODUCTION; CARBOHYDRATE-RECOGNITION DOMAIN; HUMAN ALVEOLAR MACROPHAGES; BACILLUS-CALMETTE-GUERIN; AIRWAY DENDRITIC CELLS; GRAM-NEGATIVE BACTERIA; MANNOSE-BINDING LECTIN	Because the lungs function as the body's gas-exchange organ, they are inevitably exposed to air that is contaminated with pathogens, allergens and pollutants. Host-defence mechanisms within the lungs must facilitate clearance of inhaled pathogens and particles while minimizing an inflammatory response that could damage the thin, delicate gas-exchanging epithelium. Pulmonary surfactant is a complex of lipids and proteins that enhances pathogen clearance and regulates adaptive and innate immune-cell functions. In this article, I review the structure and functions of the surfactant proteins SP-A and SP-D in regulating host immune defence and in modulating inflammatory responses.	136	478	2005	11	10.1038/nri1528	Immunology
Endogenous airway acidification - Implications for asthma pathophysiology. Airway concentrations of many reactive nitrogen and oxygen species are high In asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivites/cytotoxicities of endogenous nitrogen oxides. Here, we demonstrate that the pH of deaerated exhaled airway vapor condensate is over two log orders lower in patients with acute asthma (5.23 +/- 0.21, n = 22) than in control subjects (7.65 +/- 0.20, n = 19, p < 0.001) and normalizes with corticosteroid therapy. Values are highly reproducible, unaffected by salivary or therapeutic artifact, and identical to samples taken directly from the lower airway. Further, at these low pH values the endogenous airway compound, nitrite, is converted to nitric oxide (NO) in quantities sufficient largely to account for the concentrations of NO in asthmatic expired air, and eosinophils undergo accelerated necrosis. We speculate that airway pH may be an important determinant of expired NO concentration and airway inflammation, and suggest that regulation of airway pH has a previously unsuspected role in asthma pathophysiology.. respiratory-distress-syndrome| exhaled nitric-oxide| expired breath| sensory nerves| ph| fluid| electrophoresis| acetazolamide| inflammation| eosinophils.	MAR-2000	respiratory-distress-syndrome| exhaled nitric-oxide| expired breath| sensory nerves| ph| fluid| electrophoresis| acetazolamide| inflammation| eosinophils	Hunt, JF; Fang, KZ; Malik, R; Snyder, A; Malhotra, N; Platts-Mills, TAE; Gaston, B	Endogenous airway acidification - Implications for asthma pathophysiology		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		RESPIRATORY-DISTRESS-SYNDROME; EXHALED NITRIC-OXIDE; EXPIRED BREATH; SENSORY NERVES; PH; FLUID; ELECTROPHORESIS; ACETAZOLAMIDE; INFLAMMATION; EOSINOPHILS	Airway concentrations of many reactive nitrogen and oxygen species are high In asthma. The stability and bioactivities of these species are pH-dependent; however, the pH of the airway during acute asthma has not previously been studied. As with gastric and urinary acidification, asthmatic airway acidification could be expected dramatically to alter the concentrations and bioactivites/cytotoxicities of endogenous nitrogen oxides. Here, we demonstrate that the pH of deaerated exhaled airway vapor condensate is over two log orders lower in patients with acute asthma (5.23 +/- 0.21, n = 22) than in control subjects (7.65 +/- 0.20, n = 19, p < 0.001) and normalizes with corticosteroid therapy. Values are highly reproducible, unaffected by salivary or therapeutic artifact, and identical to samples taken directly from the lower airway. Further, at these low pH values the endogenous airway compound, nitrite, is converted to nitric oxide (NO) in quantities sufficient largely to account for the concentrations of NO in asthmatic expired air, and eosinophils undergo accelerated necrosis. We speculate that airway pH may be an important determinant of expired NO concentration and airway inflammation, and suggest that regulation of airway pH has a previously unsuspected role in asthma pathophysiology.	40	473	2000	6		General & Internal Medicine; Respiratory System
Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function. Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal-but not adult-GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.. invariant nkt cells| ulcerative-colitis| airway inflammation| hygiene hypothesis| chemokine cxcl16| b-cells| disease| asthma| colonization| antibiotics.	APR 27-2012	invariant nkt cells| ulcerative-colitis| airway inflammation| hygiene hypothesis| chemokine cxcl16| b-cells| disease| asthma| colonization| antibiotics	Olszak, T; An, DD; Zeissig, S; Vera, MP; Richter, J; Franke, A; Glickman, JN; Siebert, R; Baron, RM; Kasper, DL; Blumberg, RS	Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function		SCIENCE		INVARIANT NKT CELLS; ULCERATIVE-COLITIS; AIRWAY INFLAMMATION; HYGIENE HYPOTHESIS; CHEMOKINE CXCL16; B-CELLS; DISEASE; ASTHMA; COLONIZATION; ANTIBIOTICS	Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal-but not adult-GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.	33	471	2012	5	10.1126/science.1219328	Science & Technology - Other Topics
Worldwide burden of disease from exposure to second-hand smoke: a retrospective analysis of data from 192 countries. Background Exposure to second-hand smoke is common in many countries but the magnitude of the problem worldwide is poorly described. We aimed to estimate the worldwide exposure to second-hand smoke and its burden of disease in children and adult non-smokers in 2004. Methods The burden of disease from second-hand smoke was estimated as deaths and disability-adjusted life-years (DALYs) for children and adult non-smokers. The calculations were based on disease-specific relative risk estimates and area-specific estimates of the proportion of people exposed to second-hand smoke, by comparative risk assessment methods, with data from 192 countries during 2004. Findings Worldwide, 40% of children, 33% of male non-smokers, and 35% of female non-smokers were exposed to second-hand smoke in 2004. This exposure was estimated to have caused 379 000 deaths from ischaemic heart disease, 165 000 from lower respiratory infections, 36 900 from asthma, and 21 400 from lung cancer. 603 000 deaths were attributable to second-hand smoke in 2004, which was about 1.0% of worldwide mortality. 47% of deaths from second-hand smoke occurred in women, 28% in children, and 26% in men. DALYs lost because of exposure to second-hand smoke amounted to 10.9 million, which was about 0.7% of total worldwide burden of diseases in DALYs in 2004. 61% of DALYs were in children. The largest disease burdens were from lower respiratory infections in children younger than 5 years (5 939 000), ischaemic heart disease in adults (2 836 000), and asthma in adults (1 246 000) and children (651 000). Interpretation These estimates of worldwide burden of disease attributable to second-hand smoke suggest that substantial health gains could be made by extending effective public health and clinical interventions to reduce passive smoking worldwide.. environmental tobacco-smoke| passive smoking| health| legislation| children| impact.	JAN 8-2011	environmental tobacco-smoke| passive smoking| health| legislation| children| impact	Oberg, M; Jaakkola, MS; Woodward, A; Peruga, A; Pruss-Ustun, A	Worldwide burden of disease from exposure to second-hand smoke: a retrospective analysis of data from 192 countries		LANCET		ENVIRONMENTAL TOBACCO-SMOKE; PASSIVE SMOKING; HEALTH; LEGISLATION; CHILDREN; IMPACT	Background Exposure to second-hand smoke is common in many countries but the magnitude of the problem worldwide is poorly described. We aimed to estimate the worldwide exposure to second-hand smoke and its burden of disease in children and adult non-smokers in 2004. Methods The burden of disease from second-hand smoke was estimated as deaths and disability-adjusted life-years (DALYs) for children and adult non-smokers. The calculations were based on disease-specific relative risk estimates and area-specific estimates of the proportion of people exposed to second-hand smoke, by comparative risk assessment methods, with data from 192 countries during 2004. Findings Worldwide, 40% of children, 33% of male non-smokers, and 35% of female non-smokers were exposed to second-hand smoke in 2004. This exposure was estimated to have caused 379 000 deaths from ischaemic heart disease, 165 000 from lower respiratory infections, 36 900 from asthma, and 21 400 from lung cancer. 603 000 deaths were attributable to second-hand smoke in 2004, which was about 1.0% of worldwide mortality. 47% of deaths from second-hand smoke occurred in women, 28% in children, and 26% in men. DALYs lost because of exposure to second-hand smoke amounted to 10.9 million, which was about 0.7% of total worldwide burden of diseases in DALYs in 2004. 61% of DALYs were in children. The largest disease burdens were from lower respiratory infections in children younger than 5 years (5 939 000), ischaemic heart disease in adults (2 836 000), and asthma in adults (1 246 000) and children (651 000). Interpretation These estimates of worldwide burden of disease attributable to second-hand smoke suggest that substantial health gains could be made by extending effective public health and clinical interventions to reduce passive smoking worldwide.	38	468	2011	8	10.1016/S0140-6736(10)61388-8	General & Internal Medicine
Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. We have prospectively studied wheezing disorder and allergy in 47 children hospitalized with respiratory syncytial virus (RSV) bronchiolitis in infancy and 93 matched control subjects. Subjects with at least three episodes of wheezing were defined as recurrent wheezers and as having asthma if the episodes were doctor verified. Here we report the outcome at age 13 years in 46/47 children with RSV and 92/93 control subjects. Wheezing disorder and clinical allergy were estimated using a questionnaire. Skin prick tests were performed and serum IgE antibodies measured. Spirometry was undertaken at rest, after dry air challenge, and after beta(2)-agonist inhalation. The occurrence of symptoms over the previous 12 months was significantly higher in the RSV group than among the control subjects, 43% versus 8% for asthma/recurrent wheezing and 39% versus 15% for allergic rhinoconjunctivitis. Sensitization to common inhaled allergens was more frequent in the RSV group than in the control subjects, judged by skin prick tests (50% versus 28%; p = 0.022), or by serum IgE antibodies (45% versus 26%; p = 0.038). Compared with the control subjects, the RSV group showed mild airway obstruction both at rest and after bronchodilation, and had slightly more reactive airways. RSV bronchiolitis in infancy severe enough to cause hospitalization is a risk factor for allergic asthma in early adolescence.. airway obstruction| atopic hypersensitivity| children| respiratory syncytial virus|rsv bronchiolitis| airway function| infection| children| sensitization| life| disease| risk| mechanisms| wheeze.	JAN 15-2005	airway obstruction| atopic hypersensitivity| children| respiratory syncytial virus|rsv bronchiolitis| airway function| infection| children| sensitization| life| disease| risk| mechanisms| wheeze	Sigurs, N; Gustafsson, PM; Bjarnason, R; Lundberg, F; Schmidt, S; Sigurbergsson, F; Kjellman, B	Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	airway obstruction; atopic hypersensitivity; children; respiratory syncytial virus	RSV BRONCHIOLITIS; AIRWAY FUNCTION; INFECTION; CHILDREN; SENSITIZATION; LIFE; DISEASE; RISK; MECHANISMS; WHEEZE	We have prospectively studied wheezing disorder and allergy in 47 children hospitalized with respiratory syncytial virus (RSV) bronchiolitis in infancy and 93 matched control subjects. Subjects with at least three episodes of wheezing were defined as recurrent wheezers and as having asthma if the episodes were doctor verified. Here we report the outcome at age 13 years in 46/47 children with RSV and 92/93 control subjects. Wheezing disorder and clinical allergy were estimated using a questionnaire. Skin prick tests were performed and serum IgE antibodies measured. Spirometry was undertaken at rest, after dry air challenge, and after beta(2)-agonist inhalation. The occurrence of symptoms over the previous 12 months was significantly higher in the RSV group than among the control subjects, 43% versus 8% for asthma/recurrent wheezing and 39% versus 15% for allergic rhinoconjunctivitis. Sensitization to common inhaled allergens was more frequent in the RSV group than in the control subjects, judged by skin prick tests (50% versus 28%; p = 0.022), or by serum IgE antibodies (45% versus 26%; p = 0.038). Compared with the control subjects, the RSV group showed mild airway obstruction both at rest and after bronchodilation, and had slightly more reactive airways. RSV bronchiolitis in infancy severe enough to cause hospitalization is a risk factor for allergic asthma in early adolescence.	37	467	2005	5	10.1164/rccm.200406-730OC	General & Internal Medicine; Respiratory System
Epidemiology of fine particulate air pollution and human health: Biologic mechanisms and who's at risk?. This article briefly summarizes the epidemiology of the health effects of fine particulate air pollution, provides an early, somewhat speculative, discussion of the contribution of epidemiology to evaluating biologic mechanisms, and evaluates who's at risk or is susceptible to adverse health effects. Based on preliminary epidemiologic evidence, it is speculated that a systemic response to fine particle-induced pulmonary inflammation, including cytokine release and altered cardiac autonomic function, may be part of the pathophysiologic mechanisms or pathways linking particulate pollution with cardiopulmonary disease. The elderly, infants, and persons with chronic cardiopulmonary disease, influenza, or asthma are most susceptible to mortality and serious morbidity effects from short-term acutely elevated exposures. Others are susceptible to less serious health effects such as transient increases in respiratory symptoms, decreased lung function, or other physiologic changes. Chronic exposure studies suggest relatively broad susceptibility to cumulative effects of long-term repeated exposure to fine particulate pollution, resulting in substantive estimates of population average loss of life expectancy in highly polluted environments. Additional knowledge is needed about the specific pollutants or mix of pollutants responsible for the adverse health effects and the biologic mechanisms involved.. air pollution| cardiopulmonary disease| health effects| life expectancy| particulate pollution| review|emergency room visits| peak expiratory flow| obstructive pulmonary-disease| time-series analysis| respiratory hospital admissions| heart-rate-variability| north-american children| minneapolis st-paul| long-term exposure| santa-clara county.	AUG-2000	air pollution| cardiopulmonary disease| health effects| life expectancy| particulate pollution| review|emergency room visits| peak expiratory flow| obstructive pulmonary-disease| time-series analysis| respiratory hospital admissions| heart-rate-variability| north-american children| minneapolis st-paul| long-term exposure| santa-clara county	Pope, CA	Epidemiology of fine particulate air pollution and human health: Biologic mechanisms and who's at risk?		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; cardiopulmonary disease; health effects; life expectancy; particulate pollution; review	EMERGENCY ROOM VISITS; PEAK EXPIRATORY FLOW; OBSTRUCTIVE PULMONARY-DISEASE; TIME-SERIES ANALYSIS; RESPIRATORY HOSPITAL ADMISSIONS; HEART-RATE-VARIABILITY; NORTH-AMERICAN CHILDREN; MINNEAPOLIS ST-PAUL; LONG-TERM EXPOSURE; SANTA-CLARA COUNTY	This article briefly summarizes the epidemiology of the health effects of fine particulate air pollution, provides an early, somewhat speculative, discussion of the contribution of epidemiology to evaluating biologic mechanisms, and evaluates who's at risk or is susceptible to adverse health effects. Based on preliminary epidemiologic evidence, it is speculated that a systemic response to fine particle-induced pulmonary inflammation, including cytokine release and altered cardiac autonomic function, may be part of the pathophysiologic mechanisms or pathways linking particulate pollution with cardiopulmonary disease. The elderly, infants, and persons with chronic cardiopulmonary disease, influenza, or asthma are most susceptible to mortality and serious morbidity effects from short-term acutely elevated exposures. Others are susceptible to less serious health effects such as transient increases in respiratory symptoms, decreased lung function, or other physiologic changes. Chronic exposure studies suggest relatively broad susceptibility to cumulative effects of long-term repeated exposure to fine particulate pollution, resulting in substantive estimates of population average loss of life expectancy in highly polluted environments. Additional knowledge is needed about the specific pollutants or mix of pollutants responsible for the adverse health effects and the biologic mechanisms involved.	197	467	2000	11	10.2307/3454408	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA(+) T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27-CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27-CCR10 interactions have a pivotal role in T cell-mediated skin inflammation.. protein-coupled receptor-2| allergic dermatitis| endothelial-cells| atopic-dermatitis| cutting edge| chemokine| psoriasis| expression| antigen| binding.	FEB-2002	protein-coupled receptor-2| allergic dermatitis| endothelial-cells| atopic-dermatitis| cutting edge| chemokine| psoriasis| expression| antigen| binding	Homey, B; Alenius, H; Muller, A; Soto, H; Bowman, EP; Yuan, W; McEvoy, L; Lauerma, AI; Assmann, T; Bunemann, E; Lehto, M; Wolff, H; Yen, D; Marxhausen, H; To, W; Sedgwick, J; Ruzicka, T; Lehmann, P; Zlotnik, A	CCL27-CCR10 interactions regulate T cell-mediated skin inflammation		NATURE MEDICINE		PROTEIN-COUPLED RECEPTOR-2; ALLERGIC DERMATITIS; ENDOTHELIAL-CELLS; ATOPIC-DERMATITIS; CUTTING EDGE; CHEMOKINE; PSORIASIS; EXPRESSION; ANTIGEN; BINDING	The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epidermal basal keratinocytes produced CCL27 protein that bound to extracellular matrix, mediated adhesion and was displayed on the surface of dermal endothelial cells. Tumor necrosis factor-alpha and interleukin-1beta induced CCL27 production whereas the glucocorticosteroid clobetasol propionate suppressed it. Circulating skin-homing CLA(+) T cells, dermal microvascular endothelial cells and fibroblasts expressed CCR10 on their cell surface. In vivo, intracutaneous CCL27 injection attracted lymphocytes and, conversely, neutralization of CCL27-CCR10 interactions impaired lymphocyte recruitment to the skin leading to the suppression of allergen-induced skin inflammation. Together, these findings indicate that CCL27-CCR10 interactions have a pivotal role in T cell-mediated skin inflammation.	45	457	2002	9	10.1038/nm0202-157	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Exposure to Environmental Microorganisms and Childhood Asthma. BACKGROUND Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions. METHODS In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In one study - PARSIFAL (Prevention of Allergy - Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle) - samples of mattress dust were screened for bacterial DNA with the use of single-strand conformation polymorphism (SSCP) analyses to detect environmental bacteria that cannot be measured by means of culture techniques. In the other study - GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study) - samples of settled dust from children's rooms were evaluated for bacterial and fungal taxa with the use of culture techniques. RESULTS In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86). CONCLUSIONS Children living on farms were exposed to a wider range of microbes than were children in the reference group, and this exposure explains a substantial fraction of the inverse relation between asthma and growing up on a farm. (Funded by the Deutsche Forschungsgemeinschaft and the European Commission.). school-age-children| in-house dust| atopic sensitization| allergic diseases| farm children| mattress dust| endotoxin| bacterial| inflammation| association.	FEB 24-2011	school-age-children| in-house dust| atopic sensitization| allergic diseases| farm children| mattress dust| endotoxin| bacterial| inflammation| association	Ege, MJ; Mayer, M; Normand, AC; Genuneit, J; Cookson, WOCM; Braun-Fahrlander, C; Heederik, D; Piarroux, R; von Mutius, E	Exposure to Environmental Microorganisms and Childhood Asthma		NEW ENGLAND JOURNAL OF MEDICINE		SCHOOL-AGE-CHILDREN; IN-HOUSE DUST; ATOPIC SENSITIZATION; ALLERGIC DISEASES; FARM CHILDREN; MATTRESS DUST; ENDOTOXIN; BACTERIAL; INFLAMMATION; ASSOCIATION	BACKGROUND Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions. METHODS In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In one study - PARSIFAL (Prevention of Allergy - Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle) - samples of mattress dust were screened for bacterial DNA with the use of single-strand conformation polymorphism (SSCP) analyses to detect environmental bacteria that cannot be measured by means of culture techniques. In the other study - GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study) - samples of settled dust from children's rooms were evaluated for bacterial and fungal taxa with the use of culture techniques. RESULTS In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86). CONCLUSIONS Children living on farms were exposed to a wider range of microbes than were children in the reference group, and this exposure explains a substantial fraction of the inverse relation between asthma and growing up on a farm. (Funded by the Deutsche Forschungsgemeinschaft and the European Commission.)	27	453	2011	9	10.1056/NEJMoa1007302	General & Internal Medicine
"The diagnosis and management of rhinitis: An updated practice parameter. These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing ""The diagnosis and Management of Rhinitis: An Updated Practice Parameter"" This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for rise by pharmaceutical companies in drug promotion.. seasonal allergic rhinitis| quality-of-life| aqueous nasal spray| placebo-controlled trial| house-dust-mite| long-term treatment| dermatophagoides-pteronyssinus extract| intranasal fluticasone propionate| conjunctival provocation test| randomized controlled-trial."	AUG-2008	seasonal allergic rhinitis| quality-of-life| aqueous nasal spray| placebo-controlled trial| house-dust-mite| long-term treatment| dermatophagoides-pteronyssinus extract| intranasal fluticasone propionate| conjunctival provocation test| randomized controlled-trial	Wallace, DV; Dykewicz, MS; Bernstein, DI; Bernstein, IL; Blessing-Moore, J; Cox, L; Khan, DA; Lang, DM; Nicklas, RA; Oppenheimer, J; Portnoy, JM; Randolph, CC; Schuller, D; Spector, SL; Tilles, SA; May, KR; Miller, TA; Druce, HM; Baroody, FM; Bernstein, JA; Craig, TJ; Georgitis, JW; Pawankar, R; Rachelefsky, GS; Settipane, RA; Skoner, DP; Stoloff, SW	The diagnosis and management of rhinitis: An updated practice parameter		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY		SEASONAL ALLERGIC RHINITIS; QUALITY-OF-LIFE; AQUEOUS NASAL SPRAY; PLACEBO-CONTROLLED TRIAL; HOUSE-DUST-MITE; LONG-TERM TREATMENT; DERMATOPHAGOIDES-PTERONYSSINUS EXTRACT; INTRANASAL FLUTICASONE PROPIONATE; CONJUNCTIVAL PROVOCATION TEST; RANDOMIZED CONTROLLED-TRIAL	"These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing ""The diagnosis and Management of Rhinitis: An Updated Practice Parameter"" This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for rise by pharmaceutical companies in drug promotion."	997	453	2008	84	10.1016/j.jaci.2008.06.003	Allergy; Immunology
Polyphenols and disease risk in epidemiologic studies. Plant polyphenols, a large group of natural antioxidants, are serious candidates in explanations of the protective effects of vegetables and fruits against cancer and cardiovascular diseases. Epidemiologic studies are useful for evaluation of the human health effects of long-term exposure to physiologic concentrations of polyphenols, but reliable data on polyphenol contents of foods are still scarce. The aim of this review is to summarize available epidemiologic data on the health effects of polyphenols, focusing on the flavonoid subclasses of flavonols, flavones, and catechins and on lignans. Data obtained to date suggest beneficial effects of both flavonoids and lignans on cardiovascular diseases but not on cancer, with the possible exception of lung cancer. There is a need for more research on stroke and lung diseases such as asthma and chronic obstructive pulmonary disease. Most studies to date have included only flavonols and flavones. With data becoming available for other polyphenols, these compounds should be included in future studies. Careful design of prospective studies is important to offset some of the major drawbacks of epidemiologic studies, including residual confounding (by smoking and other dietary factors) and exposure assessment.. review| epidemiology| polyphenols| flavonoids| flavonols| catechins| lignans| antioxidants| phytoestrogens| cancer| cardiovascular diseases| stroke|coronary heart-disease| breast-cancer risk| potentially anticarcinogenic flavonoids| cardiovascular-disease| postmenopausal women| phytoestrogen intake| dietary flavonoids| united-states| male smokers| antioxidant flavonols.	JAN-2005	review| epidemiology| polyphenols| flavonoids| flavonols| catechins| lignans| antioxidants| phytoestrogens| cancer| cardiovascular diseases| stroke|coronary heart-disease| breast-cancer risk| potentially anticarcinogenic flavonoids| cardiovascular-disease| postmenopausal women| phytoestrogen intake| dietary flavonoids| united-states| male smokers| antioxidant flavonols	Arts, ICW; Hollman, PCH	Polyphenols and disease risk in epidemiologic studies		AMERICAN JOURNAL OF CLINICAL NUTRITION	review; epidemiology; polyphenols; flavonoids; flavonols; catechins; lignans; antioxidants; phytoestrogens; cancer; cardiovascular diseases; stroke	CORONARY HEART-DISEASE; BREAST-CANCER RISK; POTENTIALLY ANTICARCINOGENIC FLAVONOIDS; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; PHYTOESTROGEN INTAKE; DIETARY FLAVONOIDS; UNITED-STATES; MALE SMOKERS; ANTIOXIDANT FLAVONOLS	Plant polyphenols, a large group of natural antioxidants, are serious candidates in explanations of the protective effects of vegetables and fruits against cancer and cardiovascular diseases. Epidemiologic studies are useful for evaluation of the human health effects of long-term exposure to physiologic concentrations of polyphenols, but reliable data on polyphenol contents of foods are still scarce. The aim of this review is to summarize available epidemiologic data on the health effects of polyphenols, focusing on the flavonoid subclasses of flavonols, flavones, and catechins and on lignans. Data obtained to date suggest beneficial effects of both flavonoids and lignans on cardiovascular diseases but not on cancer, with the possible exception of lung cancer. There is a need for more research on stroke and lung diseases such as asthma and chronic obstructive pulmonary disease. Most studies to date have included only flavonols and flavones. With data becoming available for other polyphenols, these compounds should be included in future studies. Careful design of prospective studies is important to offset some of the major drawbacks of epidemiologic studies, including residual confounding (by smoking and other dietary factors) and exposure assessment.	71	452	2005	9		Nutrition & Dietetics
Relation between house-dust endotoxin exposure, type 1 T cell development, and allergen sensitisation in infants at high risk of asthma. Background Bacterial endotoxin is known to induce interferon gamma and interleukin 12 production, and therefore has the potential to decrease allergen sensitisation. To find out the role of early chronic endotoxin exposure in the development of allergen sensitisation and asthma, we compared concentrations of endotoxin in house dust with allergen sensitisation in infants at high risk for developing asthma. Methods 61 infants 9-24 months old with at. least three physician-documented episodes of wheezing were studied. Concentrations of house-dust endotoxin and allergens were measured in the infants' homes. Allergen sensitisation was measured by skin-prick testing with a panel of common inhalant and food allergens. In a subset of these infants, proportions of T lymphocytes producing interferon gamma, and interleukins 4, 5, and 13 were calculated by cell-surface and intracellular cytokine staining, with flow cytometry. Findings House-dust endotoxin concentrations ranged from 104 to 10 000 endotoxin units (EU) per mt (geometric mean 912 EU/mL). Concentrations did not vary significantly over a 6-month interval. Ten infants (16%) were sensitised to at least one allergen. The homes of allergen-sensitised infants contained significantly lower concentrations of house-dust endotoxin than those of non-sensitised infants (mean 468 vs 1035 EU/mL, respectively; p=0.01). Increased house-dust endotoxin concentrations correlated with increased proportions of interferon-gamma-producing CD4 T cells (p=0.01). Such concentrations did not correlate with proportions of cells that produced interleukins 4, 5, or 13. Interpretation This study may provide the first direct in-vivo evidence that indoor endotoxin exposure early in life may protect against allergen sensitisation by enhancing type 1 immunity.. interferon-gamma production| blood mononuclear-cells| peripheral-blood| children| atopy| prevalence| sensitization| association| responses| interleukin-4.	MAY 13-2000	interferon-gamma production| blood mononuclear-cells| peripheral-blood| children| atopy| prevalence| sensitization| association| responses| interleukin-4	Gereda, JE; Leung, DYM; Thatayatikom, A; Streib, JE; Price, MR; Klinnert, MD; Liu, AH	Relation between house-dust endotoxin exposure, type 1 T cell development, and allergen sensitisation in infants at high risk of asthma		LANCET		INTERFERON-GAMMA PRODUCTION; BLOOD MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; CHILDREN; ATOPY; PREVALENCE; SENSITIZATION; ASSOCIATION; RESPONSES; INTERLEUKIN-4	Background Bacterial endotoxin is known to induce interferon gamma and interleukin 12 production, and therefore has the potential to decrease allergen sensitisation. To find out the role of early chronic endotoxin exposure in the development of allergen sensitisation and asthma, we compared concentrations of endotoxin in house dust with allergen sensitisation in infants at high risk for developing asthma. Methods 61 infants 9-24 months old with at. least three physician-documented episodes of wheezing were studied. Concentrations of house-dust endotoxin and allergens were measured in the infants' homes. Allergen sensitisation was measured by skin-prick testing with a panel of common inhalant and food allergens. In a subset of these infants, proportions of T lymphocytes producing interferon gamma, and interleukins 4, 5, and 13 were calculated by cell-surface and intracellular cytokine staining, with flow cytometry. Findings House-dust endotoxin concentrations ranged from 104 to 10 000 endotoxin units (EU) per mt (geometric mean 912 EU/mL). Concentrations did not vary significantly over a 6-month interval. Ten infants (16%) were sensitised to at least one allergen. The homes of allergen-sensitised infants contained significantly lower concentrations of house-dust endotoxin than those of non-sensitised infants (mean 468 vs 1035 EU/mL, respectively; p=0.01). Increased house-dust endotoxin concentrations correlated with increased proportions of interferon-gamma-producing CD4 T cells (p=0.01). Such concentrations did not correlate with proportions of cells that produced interleukins 4, 5, or 13. Interpretation This study may provide the first direct in-vivo evidence that indoor endotoxin exposure early in life may protect against allergen sensitisation by enhancing type 1 immunity.	35	449	2000	4	10.1016/S0140-6736(00)02239-X	General & Internal Medicine
Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Background In a prospective birth-cohort study, we assessed the relevance of mite and cat allergen exposure for the development of childhood asthma up to age 7 years. Methods Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available far 939 children. Assessments included repeated measurement of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months, and 3 years of age, and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial hyper-responsiveness was measured in 645 children. Findings At age 7, the prevalence of wheezing in the past 12 months was 10.0% (94 of 938), and 6.1% (57 of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze, and increased bronchial responsiveness. However, no relation between early indoor allergen exposure and the prevalence of asthma, wheeze, and bronchial hyper-responsiveness was seen. Interpretation Our data do not support the hypothesis that exposure to environmental allergens causes asthma in childhood, but rather that the induction of specific IgE responses and the development of childhood asthma are determined by independent factors.. skin-test reactivity| risk factor| sensitization| children| association| altitude| fel-d-1.	OCT 21-2000	skin-test reactivity| risk factor| sensitization| children| association| altitude| fel-d-1	Lau, S; Illi, S; Sommerfeld, C; Niggemann, B; Bergmann, R; von Mutius, E; Wahn, U	Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study		LANCET		SKIN-TEST REACTIVITY; RISK FACTOR; SENSITIZATION; CHILDREN; ASSOCIATION; ALTITUDE; FEL-D-1	Background In a prospective birth-cohort study, we assessed the relevance of mite and cat allergen exposure for the development of childhood asthma up to age 7 years. Methods Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available far 939 children. Assessments included repeated measurement of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months, and 3 years of age, and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial hyper-responsiveness was measured in 645 children. Findings At age 7, the prevalence of wheezing in the past 12 months was 10.0% (94 of 938), and 6.1% (57 of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze, and increased bronchial responsiveness. However, no relation between early indoor allergen exposure and the prevalence of asthma, wheeze, and bronchial hyper-responsiveness was seen. Interpretation Our data do not support the hypothesis that exposure to environmental allergens causes asthma in childhood, but rather that the induction of specific IgE responses and the development of childhood asthma are determined by independent factors.	35	445	2000	6	10.1016/S0140-6736(00)02842-7	General & Internal Medicine
Epidemiological evidence of effects of coarse airborne particles on health. Studies on health effects of airborne particulate matter (PM) have traditionally focused on particles <10 mu m in diameter (PM10) or particles <2.5 mu m in diameter (PM2.5). The coarse fraction of PM10, particles >2.5 mu m, has only been studied recently. These particles have different sources and composition compared with PM2.5. This paper is based on a systematic review of studies that have analysed fine and coarse PM jointly and examines the epidemiological evidence for effects of coarse particles on health. Time series studies relating ambient PM to mortality have in some places provided evidence of an independent effect of coarse PM on daily mortality, but in most urban areas, the evidence is stronger for fine particles. The few long-term studies of effects of coarse PM on survival do not provide any evidence of association. In studies of chronic obstructive pulmonary disease, asthma and respiratory admissions, coarse PM has a stronger or as strong short-term effect as fine PM, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions. There is also support for an association between coarse PM and cardiovascular admissions. It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles.. air pollution| coarse particles| epidemiology| morbidity| mortality|particulate air-pollution| southern california children| lung-function growth| daily mortality| hospital admissions| fine particles| urban air| respiratory-diseases| time-series| association.	AUG-2005	air pollution| coarse particles| epidemiology| morbidity| mortality|particulate air-pollution| southern california children| lung-function growth| daily mortality| hospital admissions| fine particles| urban air| respiratory-diseases| time-series| association	Brunekreef, B; Forsberg, B	Epidemiological evidence of effects of coarse airborne particles on health		EUROPEAN RESPIRATORY JOURNAL	air pollution; coarse particles; epidemiology; morbidity; mortality	PARTICULATE AIR-POLLUTION; SOUTHERN CALIFORNIA CHILDREN; LUNG-FUNCTION GROWTH; DAILY MORTALITY; HOSPITAL ADMISSIONS; FINE PARTICLES; URBAN AIR; RESPIRATORY-DISEASES; TIME-SERIES; ASSOCIATION	Studies on health effects of airborne particulate matter (PM) have traditionally focused on particles <10 mu m in diameter (PM10) or particles <2.5 mu m in diameter (PM2.5). The coarse fraction of PM10, particles >2.5 mu m, has only been studied recently. These particles have different sources and composition compared with PM2.5. This paper is based on a systematic review of studies that have analysed fine and coarse PM jointly and examines the epidemiological evidence for effects of coarse particles on health. Time series studies relating ambient PM to mortality have in some places provided evidence of an independent effect of coarse PM on daily mortality, but in most urban areas, the evidence is stronger for fine particles. The few long-term studies of effects of coarse PM on survival do not provide any evidence of association. In studies of chronic obstructive pulmonary disease, asthma and respiratory admissions, coarse PM has a stronger or as strong short-term effect as fine PM, suggesting that coarse PM may lead to adverse responses in the lungs triggering processes leading to hospital admissions. There is also support for an association between coarse PM and cardiovascular admissions. It is concluded that special consideration should be given to studying and regulating coarse particles separately from fine particles.	58	440	2005	10	10.1183/09031936.05.00001805	Respiratory System
Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study. Objective To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies. Design Retrospective case-control study. Participants 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24. Setting Air force school in Caserta, Italy. Main outcome measures Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis, Results Compared with controls there tvas a lower prevalence of T gondii (26% v 18%, P = 0.027), hepatitis A virus (30% v 16%, P = 0.004), and H pylori (18% v 15%, P = 0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0.70; two or three, 0.37; P for trend = 0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus). Conclusion Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.. family-size| serum ige| association| infections| prevalence| childhood| diseases| hygiene| cells| flora.	FEB 12-2000	family-size| serum ige| association| infections| prevalence| childhood| diseases| hygiene| cells| flora	Matricardi, PM; Rosmini, F; Riondino, S; Fortini, M; Ferrigno, L; Rapicetta, M; Bonini, S	Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study		BRITISH MEDICAL JOURNAL		FAMILY-SIZE; SERUM IGE; ASSOCIATION; INFECTIONS; PREVALENCE; CHILDHOOD; DISEASES; HYGIENE; CELLS; FLORA	Objective To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies. Design Retrospective case-control study. Participants 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24. Setting Air force school in Caserta, Italy. Main outcome measures Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis, Results Compared with controls there tvas a lower prevalence of T gondii (26% v 18%, P = 0.027), hepatitis A virus (30% v 16%, P = 0.004), and H pylori (18% v 15%, P = 0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0.70; two or three, 0.37; P for trend = 0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus). Conclusion Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.	36	440	2000	6	10.1136/bmj.320.7232.412	General & Internal Medicine
Atopic dermatitis: New insights and opportunities for therapeutic intervention. Atopic dermatitis (AD) is a chronic inflammatory skin disease that frequently predates the development of allergic rhinitis or asthma. It is an important skin condition with significant costs and morbidity to patients and their families; the disease affects more than 10% of children. Recent studies have demonstrated the complex interrelationship of genetic, environmental, skin barrier, pharmacologic, psychologic, and immunologic factors that contribute to the development and severity of AD. The current review will examine the cellular and molecular mechanisms that contribute to AD as well as the immunologic triggers involved in its pathogenesis. These insights provide new opportunities for therapeutic intervention in this common skin condition.. atopic dermatitis| keratinocytes| t cells| hypersensitivity| skin| allergy| superantigens| ige|dose intravenous immunoglobulin| lymphocyte-associated antigen| epidermal langerhans cells| colony-stimulating factor| interferon-gamma-therapy| high-affinity receptor| in-vivo expression| house-dust mite| memory t-cells| fc-epsilon-ri.	MAY-2000	atopic dermatitis| keratinocytes| t cells| hypersensitivity| skin| allergy| superantigens| ige|dose intravenous immunoglobulin| lymphocyte-associated antigen| epidermal langerhans cells| colony-stimulating factor| interferon-gamma-therapy| high-affinity receptor| in-vivo expression| house-dust mite| memory t-cells| fc-epsilon-ri	Leung, DYM	Atopic dermatitis: New insights and opportunities for therapeutic intervention		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopic dermatitis; keratinocytes; T cells; hypersensitivity; skin; allergy; superantigens; IgE	DOSE INTRAVENOUS IMMUNOGLOBULIN; LYMPHOCYTE-ASSOCIATED ANTIGEN; EPIDERMAL LANGERHANS CELLS; COLONY-STIMULATING FACTOR; INTERFERON-GAMMA-THERAPY; HIGH-AFFINITY RECEPTOR; IN-VIVO EXPRESSION; HOUSE-DUST MITE; MEMORY T-CELLS; FC-EPSILON-RI	Atopic dermatitis (AD) is a chronic inflammatory skin disease that frequently predates the development of allergic rhinitis or asthma. It is an important skin condition with significant costs and morbidity to patients and their families; the disease affects more than 10% of children. Recent studies have demonstrated the complex interrelationship of genetic, environmental, skin barrier, pharmacologic, psychologic, and immunologic factors that contribute to the development and severity of AD. The current review will examine the cellular and molecular mechanisms that contribute to AD as well as the immunologic triggers involved in its pathogenesis. These insights provide new opportunities for therapeutic intervention in this common skin condition.	147	439	2000	17	10.1067/mai.2000.106484	Allergy; Immunology
Immortal time bias in pharmacoepidemiology. Immortal time is a span of cohort follow-up during which, because of exposure definition, the outcome under study could not occur. Bias from immortal time was first identified in the 1970s in epidemiology in the context of cohort studies of the survival benefit of heart transplantation. It recently resurfaced in pharmacoepidemiology, with several observational studies reporting that various medications can be extremely effective at reducing morbidity and mortality. These studies, while using different cohort designs, all involved some form of immortal time and the corresponding bias. In this paper, the author describes various cohort study designs leading to this bias, quantifies its magnitude under different survival distributions, and illustrates it by using data from a cohort of lung cancer patients. The author shows that for time-based, event-based, and exposure-based cohort definitions, the bias in the rate ratio resulting from misclassified or excluded immortal time increases proportionately to the duration of immortal time. The bias is more pronounced with a decreasing hazard function for the outcome event, as illustrated with the Weibull distribution compared with a constant hazard from the exponential distribution. In conclusion, observational studies of drug benefit in which computerized databases are used must be designed and analyzed properly to avoid immortal time bias.. bias (epidemiology)| cohort studies| databases| epidemiologic methods| pharmaceutical preparations| relative biological effectiveness| statistics| treatment outcome|obstructive pulmonary-disease| acute myocardial-infarction| inhaled corticosteroids| cardiac transplantation| asthma| risk| mortality| survival| copd| steroids.	FEB 15-2008	bias (epidemiology)| cohort studies| databases| epidemiologic methods| pharmaceutical preparations| relative biological effectiveness| statistics| treatment outcome|obstructive pulmonary-disease| acute myocardial-infarction| inhaled corticosteroids| cardiac transplantation| asthma| risk| mortality| survival| copd| steroids	Suissa, S	Immortal time bias in pharmacoepidemiology		AMERICAN JOURNAL OF EPIDEMIOLOGY	bias (epidemiology); cohort studies; databases; epidemiologic methods; pharmaceutical preparations; relative biological effectiveness; statistics; treatment outcome	OBSTRUCTIVE PULMONARY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; INHALED CORTICOSTEROIDS; CARDIAC TRANSPLANTATION; ASTHMA; RISK; MORTALITY; SURVIVAL; COPD; STEROIDS	Immortal time is a span of cohort follow-up during which, because of exposure definition, the outcome under study could not occur. Bias from immortal time was first identified in the 1970s in epidemiology in the context of cohort studies of the survival benefit of heart transplantation. It recently resurfaced in pharmacoepidemiology, with several observational studies reporting that various medications can be extremely effective at reducing morbidity and mortality. These studies, while using different cohort designs, all involved some form of immortal time and the corresponding bias. In this paper, the author describes various cohort study designs leading to this bias, quantifies its magnitude under different survival distributions, and illustrates it by using data from a cohort of lung cancer patients. The author shows that for time-based, event-based, and exposure-based cohort definitions, the bias in the rate ratio resulting from misclassified or excluded immortal time increases proportionately to the duration of immortal time. The bias is more pronounced with a decreasing hazard function for the outcome event, as illustrated with the Weibull distribution compared with a constant hazard from the exponential distribution. In conclusion, observational studies of drug benefit in which computerized databases are used must be designed and analyzed properly to avoid immortal time bias.	40	434	2008	8	10.1093/aje/kwm324	Public, Environmental & Occupational Health
Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Background: Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important. Objective: The goal of the Severe Asthma Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. Methods: We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma. Results: A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration (P < .0001), more daily symptoms, intense urgent health care utilization, sinusitis, and pneumonia (P < .0001). Lung function was lower in severe asthma with marked bronchodilator reversibility (P < .001). The severe group had less atopy by skin tests (P = .0007), but blood eosinophils, IgE, and exhaled nitric oxide levels did not differentiate disease severity. A reduced FEV1, history of pneumonia, and fewer positive skin tests were risk factors for severe disease. Early disease onset (age < 12 years) in severe asthma was associated with longer disease duration (P < .0001) and more urgent health care, especially intensive care (P = .002). Later disease onset (age >= 12 years) was associated with lower lung function and sinopulmonary infections (P <= .02). Conclusion: Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization. Clinical implications: Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.. severe asthma| definition| bronchodilator response| pathophysiology| phenotype| pneumonia|exhaled nitric-oxide| air-flow obstruction| near-fatal asthma| to-treat asthma| inhaled-corticosteroids| risk-factors| eosinophilic inflammation| disease| adults| exacerbations.	FEB-2007	severe asthma| definition| bronchodilator response| pathophysiology| phenotype| pneumonia|exhaled nitric-oxide| air-flow obstruction| near-fatal asthma| to-treat asthma| inhaled-corticosteroids| risk-factors| eosinophilic inflammation| disease| adults| exacerbations	Moore, WC; Bleecker, ER; Curran-Everett, D; Erzurum, SC; Ameredes, BT; Bacharier, L; Calhoun, WJ; Castro, M; Chung, KF; Clark, MP; Dweik, RA; Fitzpatrick, AM; Gaston, B; Hew, M; Hussain, I; Jarjour, NN; Israel, E; Levy, BD; Murphy, JR; Peters, SP; Teague, WG; Meyers, DA; Busse, WW; Wenzel, SE	Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	severe asthma; definition; bronchodilator response; pathophysiology; phenotype; pneumonia	EXHALED NITRIC-OXIDE; AIR-FLOW OBSTRUCTION; NEAR-FATAL ASTHMA; TO-TREAT ASTHMA; INHALED-CORTICOSTEROIDS; RISK-FACTORS; EOSINOPHILIC INFLAMMATION; DISEASE; ADULTS; EXACERBATIONS	Background: Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important. Objective: The goal of the Severe Asthma Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. Methods: We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma. Results: A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration (P < .0001), more daily symptoms, intense urgent health care utilization, sinusitis, and pneumonia (P < .0001). Lung function was lower in severe asthma with marked bronchodilator reversibility (P < .001). The severe group had less atopy by skin tests (P = .0007), but blood eosinophils, IgE, and exhaled nitric oxide levels did not differentiate disease severity. A reduced FEV1, history of pneumonia, and fewer positive skin tests were risk factors for severe disease. Early disease onset (age < 12 years) in severe asthma was associated with longer disease duration (P < .0001) and more urgent health care, especially intensive care (P = .002). Later disease onset (age >= 12 years) was associated with lower lung function and sinopulmonary infections (P <= .02). Conclusion: Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization. Clinical implications: Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.	43	434	2007	9	10.1016/j.jaci.2006.11.639	Allergy; Immunology
Allergenic pollen and pollen allergy in Europe. The allergenic content of the atmosphere varies according to climate, geography and vegetation. Data on the presence and prevalence of allergenic airborne pollens, obtained from both aerobiological studies and allergological investigations, make it possible to design pollen calendars with the approximate flowering period of the plants in the sampling area. In this way, even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas.Aerobiological and allergological studies show that the pollen map of Europe is changing also as a result of cultural factors (for example, importation of plants such as birch and cypress for urban parklands), greater international travel (e.g. colonization by ragweed in France, northern Italy, Austria, Hungary etc.) and climate change. In this regard, the higher frequency of weather extremes, like thunderstorms, and increasing episodes of long range transport of allergenic pollen represent new challenges for researchers.Furthermore, in the last few years, experimental data on pollen and subpollen-particles structure, the pathogenetic role of pollen and the interaction between pollen and air pollutants, gave new insights into the mechanisms of respiratory allergic diseases.. airway hypersensitivity| allergenic pollens| allergic asthma| allergic rhinitis| bronchial asthma| outdoor air-pollution| pollinosis| respiratory allergy| seasonal allergy.|ragweed ambrosia-artemisiifolia| respiratory health survey| long-distance transport| benjamina weeping fig| natural-rubber latex| alpha-linolenic acid| grass-pollen| ficus-benjamina| birch-pollen| environmental-factors.	SEP-2007	airway hypersensitivity| allergenic pollens| allergic asthma| allergic rhinitis| bronchial asthma| outdoor air-pollution| pollinosis| respiratory allergy| seasonal allergy.|ragweed ambrosia-artemisiifolia| respiratory health survey| long-distance transport| benjamina weeping fig| natural-rubber latex| alpha-linolenic acid| grass-pollen| ficus-benjamina| birch-pollen| environmental-factors	D'Amato, G; Cecchi, L; Bonini, S; Nunes, C; Annesi-Maesano, I; Behrendt, H; Liccardi, G; Popov, T; van Cauwenberge, P	Allergenic pollen and pollen allergy in Europe		ALLERGY	airway hypersensitivity; allergenic pollens; allergic asthma; allergic rhinitis; bronchial asthma; outdoor air-pollution; pollinosis; respiratory allergy; seasonal allergy.	RAGWEED AMBROSIA-ARTEMISIIFOLIA; RESPIRATORY HEALTH SURVEY; LONG-DISTANCE TRANSPORT; BENJAMINA WEEPING FIG; NATURAL-RUBBER LATEX; ALPHA-LINOLENIC ACID; GRASS-POLLEN; FICUS-BENJAMINA; BIRCH-POLLEN; ENVIRONMENTAL-FACTORS	The allergenic content of the atmosphere varies according to climate, geography and vegetation. Data on the presence and prevalence of allergenic airborne pollens, obtained from both aerobiological studies and allergological investigations, make it possible to design pollen calendars with the approximate flowering period of the plants in the sampling area. In this way, even though pollen production and dispersal from year to year depend on the patterns of preseason weather and on the conditions prevailing at the time of anthesis, it is usually possible to forecast the chances of encountering high atmospheric allergenic pollen concentrations in different areas.Aerobiological and allergological studies show that the pollen map of Europe is changing also as a result of cultural factors (for example, importation of plants such as birch and cypress for urban parklands), greater international travel (e.g. colonization by ragweed in France, northern Italy, Austria, Hungary etc.) and climate change. In this regard, the higher frequency of weather extremes, like thunderstorms, and increasing episodes of long range transport of allergenic pollen represent new challenges for researchers.Furthermore, in the last few years, experimental data on pollen and subpollen-particles structure, the pathogenetic role of pollen and the interaction between pollen and air pollutants, gave new insights into the mechanisms of respiratory allergic diseases.	190	433	2007	15	10.1111/j.1398-9995.2007.01393.x	Allergy; Immunology
Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Background Most of the effort directed at understanding the role infections have in preventing allergy has focused on bacteria and viruses and their ability to divert the immune system towards T-helper-1 responses and away from proallergic T-helper-2 responses. However, helminth infections, highly prevalent in large parts of the developing world, where allergy is uncommon, stimulate strong T-helper-2 responses. We investigated the influence of chronic helminth infections on the prevalence of atopy and aimed to understand the relation at a detailed immunological level. Methods 520 Gabonese schoolchildren were tested for shin reaction to house-dust mite and other allergens, for Schistosoma haematobium eggs In urine, and for microfilariae in blood samples. Total and mite-specific IgE antibodies were measured. A subsample selected on the basis of their skin test to house-dust mite received detailed immunological investigations. Findings Children with urinary schistosomiasis had a lower prevalence of a positive skin reaction to house-dust mite than those free of this infection (odds ratio 0.32 [95% CI 0.16-0.63]). The degree of sensitisation to house-dust mite could not explain this difference in skin-prick positivity. Schistosome-antigen-specific concentrations of interleukin-10 were significantly higher in infected children, and higher specific concentrations of this anti-inflammatory cytokine were negatively associated with the outcome of skin-test reactivity to mite (0.53 [0.30-0.96]). No association between polyclonal IgE antibodies and skin-test results was found. Interpretation The anti-inflammatory cytokine, interleukin-10, induced in chronic schistosomiasis, appears central to suppressing atopy in African children.. human lymphatic filariasis| allergic reactivity| cytokine control| cell responses| asthma| modulation| activation| induction| antibody| cd4(+).	NOV 18-2000	human lymphatic filariasis| allergic reactivity| cytokine control| cell responses| asthma| modulation| activation| induction| antibody| cd4(+)	van den Biggelaar, AHJ; van Ree, R; Rodrigues, LC; Lell, B; Deelder, AM; Kremsner, PG; Yazdanbakhsh, M	Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10		LANCET		HUMAN LYMPHATIC FILARIASIS; ALLERGIC REACTIVITY; CYTOKINE CONTROL; CELL RESPONSES; ASTHMA; MODULATION; ACTIVATION; INDUCTION; ANTIBODY; CD4(+)	Background Most of the effort directed at understanding the role infections have in preventing allergy has focused on bacteria and viruses and their ability to divert the immune system towards T-helper-1 responses and away from proallergic T-helper-2 responses. However, helminth infections, highly prevalent in large parts of the developing world, where allergy is uncommon, stimulate strong T-helper-2 responses. We investigated the influence of chronic helminth infections on the prevalence of atopy and aimed to understand the relation at a detailed immunological level. Methods 520 Gabonese schoolchildren were tested for shin reaction to house-dust mite and other allergens, for Schistosoma haematobium eggs In urine, and for microfilariae in blood samples. Total and mite-specific IgE antibodies were measured. A subsample selected on the basis of their skin test to house-dust mite received detailed immunological investigations. Findings Children with urinary schistosomiasis had a lower prevalence of a positive skin reaction to house-dust mite than those free of this infection (odds ratio 0.32 [95% CI 0.16-0.63]). The degree of sensitisation to house-dust mite could not explain this difference in skin-prick positivity. Schistosome-antigen-specific concentrations of interleukin-10 were significantly higher in infected children, and higher specific concentrations of this anti-inflammatory cytokine were negatively associated with the outcome of skin-test reactivity to mite (0.53 [0.30-0.96]). No association between polyclonal IgE antibodies and skin-test results was found. Interpretation The anti-inflammatory cytokine, interleukin-10, induced in chronic schistosomiasis, appears central to suppressing atopy in African children.	30	425	2000	5	10.1016/S0140-6736(00)03206-2	General & Internal Medicine
Epidemiology of primary brain tumors: Current concepts and review of the literature. The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines.. central-nervous-system| francisco bay area| petrochemical research facility| occupational risk-factors| acute lymphoblastic-leukemia| international case-control| magnetic-field exposure| vinyl-chloride workers| growth-factor receptor| cellular-telephone use.	OCT-2002	central-nervous-system| francisco bay area| petrochemical research facility| occupational risk-factors| acute lymphoblastic-leukemia| international case-control| magnetic-field exposure| vinyl-chloride workers| growth-factor receptor| cellular-telephone use	Wrensch, M; Minn, Y; Chew, T; Bondy, M; Berger, MS	Epidemiology of primary brain tumors: Current concepts and review of the literature		NEURO-ONCOLOGY		CENTRAL-NERVOUS-SYSTEM; FRANCISCO BAY AREA; PETROCHEMICAL RESEARCH FACILITY; OCCUPATIONAL RISK-FACTORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; INTERNATIONAL CASE-CONTROL; MAGNETIC-FIELD EXPOSURE; VINYL-CHLORIDE WORKERS; GROWTH-FACTOR RECEPTOR; CELLULAR-TELEPHONE USE	The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines.	214	423	2002	22	10.1215/15228517-4-4-278	Oncology; Neurosciences & Neurology
"International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ""uncontrolled"" or that remains ""uncontrolled"" despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.. exhaled nitric-oxide| air-flow obstruction| randomized controlled-trial| placebo-controlled trial| severe persistent asthma| poorly controlled asthma| genome-wide association| relative corticosteroid insensitivity| sputum eosinophil counts| allergic airways disease."	FEB-2014	exhaled nitric-oxide| air-flow obstruction| randomized controlled-trial| placebo-controlled trial| severe persistent asthma| poorly controlled asthma| genome-wide association| relative corticosteroid insensitivity| sputum eosinophil counts| allergic airways disease	Chung, KF; Wenzel, SE; Brozek, JL; Bush, A; Castro, M; Sterk, PJ; Adcock, IM; Bateman, ED; Bel, EH; Bleecker, ER; Boulet, LP; Brightling, C; Chanez, P; Dahlen, SE; Djukanovic, R; Frey, U; Gaga, M; Gibson, P; Hamid, Q; Jajour, NN; Mauad, T; Sorkness, RL; Teague, WG	International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma		EUROPEAN RESPIRATORY JOURNAL		EXHALED NITRIC-OXIDE; AIR-FLOW OBSTRUCTION; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; SEVERE PERSISTENT ASTHMA; POORLY CONTROLLED ASTHMA; GENOME-WIDE ASSOCIATION; RELATIVE CORTICOSTEROID INSENSITIVITY; SPUTUM EOSINOPHIL COUNTS; ALLERGIC AIRWAYS DISEASE	"Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ""uncontrolled"" or that remains ""uncontrolled"" despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy."	222	420	2014	31	10.1183/09031936.00202013	Respiratory System
Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy, particularly the sublingual route. The objective was to evaluate the efficacy of sublingual immunotherapy (SLIT), compared with placebo, for reductions in symptoms and medication requirements. The Cochrane Controlled Clinical Trials Register, MEDLINE (1966-2002), EMBASE (1974-2002) and Scisearch were searched, up to September 2002, using the terms (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). All studies identified by the searches were assessed by the reviewers to identify Randomized Controlled Trials involving participants with symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT or corresponding placebo. Data from identified studies was abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.1. Analysis was performed by the method of standardized mean differences (SMD) using a random effects model. P-values < 0.05 were considered statistically significant. Subgroup analyses were performed according to the type of allergen administered, the age of participants and the duration of treatment. Twenty-two trials involving 979 patients, were included. There were six trials of SLIT for house dust mite allergy, five for grass pollen, five for parietaria, two for olive and one each for, ragweed, cat, tree and cupressus. Five studies enrolled exclusively children. Seventeen studies administered the allergen by sublingual drops subsequently swallowed, three by drops subsequently spat out and two by sublingual tablets. Eight studies involved treatment for less than 6 months, 10 studies for 6-12 months and four studies for greater than 12 months. All included studies were double-blind placebo-controlled trials of parallell group design. Concealment of treatment allocation was considered adequate in all studies and the use of identical placebo preparations was almost universal. There was significant heterogeneity, most likely due to widely differing scoring systems between studies, for most comparisons. Overall there was a significant reduction in both symptoms (SMD -0.42, 95% confidence interval -0.69 to -0.15; P = 0.002) and medication requirements [SMD -0.43 (-0.63, -0.23); P = 0.00003] following immunotherapy. Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered. There was no significant reduction in symptoms and medication scores in those studies involving only children but total numbers of participants was too small to make this a reliable conclusion. Increasing duration of treatment does not clearly increase efficacy. The total dose of allergen administered may be important but insufficient data was available to analyse this factor.. allergic rhinitis| immunotherapy| sublingual| systematic review|placebo-controlled evaluation| house-dust-mite| randomized controlled-trial| parietaria-judaica extract| grass-pollen immunotherapy| double-blind| swallow immunotherapy| hay-fever| seasonal rhinitis| rhinoconjunctivitis.	JAN-2005	allergic rhinitis| immunotherapy| sublingual| systematic review|placebo-controlled evaluation| house-dust-mite| randomized controlled-trial| parietaria-judaica extract| grass-pollen immunotherapy| double-blind| swallow immunotherapy| hay-fever| seasonal rhinitis| rhinoconjunctivitis	Wilson, DR; Lima, MT; Durham, SR	Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis		ALLERGY	allergic rhinitis; immunotherapy; sublingual; systematic review	PLACEBO-CONTROLLED EVALUATION; HOUSE-DUST-MITE; RANDOMIZED CONTROLLED-TRIAL; PARIETARIA-JUDAICA EXTRACT; GRASS-POLLEN IMMUNOTHERAPY; DOUBLE-BLIND; SWALLOW IMMUNOTHERAPY; HAY-FEVER; SEASONAL RHINITIS; RHINOCONJUNCTIVITIS	Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy, particularly the sublingual route. The objective was to evaluate the efficacy of sublingual immunotherapy (SLIT), compared with placebo, for reductions in symptoms and medication requirements. The Cochrane Controlled Clinical Trials Register, MEDLINE (1966-2002), EMBASE (1974-2002) and Scisearch were searched, up to September 2002, using the terms (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). All studies identified by the searches were assessed by the reviewers to identify Randomized Controlled Trials involving participants with symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT or corresponding placebo. Data from identified studies was abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.1. Analysis was performed by the method of standardized mean differences (SMD) using a random effects model. P-values < 0.05 were considered statistically significant. Subgroup analyses were performed according to the type of allergen administered, the age of participants and the duration of treatment. Twenty-two trials involving 979 patients, were included. There were six trials of SLIT for house dust mite allergy, five for grass pollen, five for parietaria, two for olive and one each for, ragweed, cat, tree and cupressus. Five studies enrolled exclusively children. Seventeen studies administered the allergen by sublingual drops subsequently swallowed, three by drops subsequently spat out and two by sublingual tablets. Eight studies involved treatment for less than 6 months, 10 studies for 6-12 months and four studies for greater than 12 months. All included studies were double-blind placebo-controlled trials of parallell group design. Concealment of treatment allocation was considered adequate in all studies and the use of identical placebo preparations was almost universal. There was significant heterogeneity, most likely due to widely differing scoring systems between studies, for most comparisons. Overall there was a significant reduction in both symptoms (SMD -0.42, 95% confidence interval -0.69 to -0.15; P = 0.002) and medication requirements [SMD -0.43 (-0.63, -0.23); P = 0.00003] following immunotherapy. Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered. There was no significant reduction in symptoms and medication scores in those studies involving only children but total numbers of participants was too small to make this a reliable conclusion. Increasing duration of treatment does not clearly increase efficacy. The total dose of allergen administered may be important but insufficient data was available to analyse this factor.	30	419	2005	9	10.1111/j.1398-9995.2005.00699.x	Allergy; Immunology
Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Human asthma is associated with airway infiltration by T helper 2 (T(H)2) lymphocytes. We observed reduced expression of the T(H)1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4(+) cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma, Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.. hyperresponsiveness| inflammation| cells| th2.	JAN 11-2002	hyperresponsiveness| inflammation| cells| th2	Finotto, S; Neurath, MF; Glickman, JN; Qin, SX; Lehr, HA; Green, FHY; Ackerman, K; Haley, K; Gatte, PR; Szabo, SJ; Drazen, JM; De Sanctis, GT; Glimcher, LH	Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet		SCIENCE		HYPERRESPONSIVENESS; INFLAMMATION; CELLS; TH2	Human asthma is associated with airway infiltration by T helper 2 (T(H)2) lymphocytes. We observed reduced expression of the T(H)1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4(+) cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma, Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.	16	418	2002	3	10.1126/science.1065544	Science & Technology - Other Topics
Immunological mechanisms of allergen-specific immunotherapy. Allergen-specific immunotherapy has been carried out for almost a century and remains one of the few antigen-specific treatments for inflammatory diseases. The mechanisms by which allergen-specific immunotherapy exerts its effects include the modulation of both T-cell and B-cell responses to allergen. There is a strong rationale for improving the efficacy of allergen-specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem include the use of modified allergens, novel adjuvants and alternative routes of administration. This article reviews the development of allergen-specific immunotherapy, our current understanding of its mechanisms of action and its future prospects.. grass-pollen immunotherapy| randomized controlled-trial| t-cell epitopes| igg monoclonal-antibodies| monophosphoryl-lipid-a| major peanut allergen| house-dust mite| bet v 1| sublingual immunotherapy| birch-pollen.	OCT-2006	grass-pollen immunotherapy| randomized controlled-trial| t-cell epitopes| igg monoclonal-antibodies| monophosphoryl-lipid-a| major peanut allergen| house-dust mite| bet v 1| sublingual immunotherapy| birch-pollen	Larche, M; Akdis, CA; Valenta, R	Immunological mechanisms of allergen-specific immunotherapy		NATURE REVIEWS IMMUNOLOGY		GRASS-POLLEN IMMUNOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; T-CELL EPITOPES; IGG MONOCLONAL-ANTIBODIES; MONOPHOSPHORYL-LIPID-A; MAJOR PEANUT ALLERGEN; HOUSE-DUST MITE; BET V 1; SUBLINGUAL IMMUNOTHERAPY; BIRCH-POLLEN	Allergen-specific immunotherapy has been carried out for almost a century and remains one of the few antigen-specific treatments for inflammatory diseases. The mechanisms by which allergen-specific immunotherapy exerts its effects include the modulation of both T-cell and B-cell responses to allergen. There is a strong rationale for improving the efficacy of allergen-specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem include the use of modified allergens, novel adjuvants and alternative routes of administration. This article reviews the development of allergen-specific immunotherapy, our current understanding of its mechanisms of action and its future prospects.	145	417	2006	11	10.1038/nri1934	Immunology
Prenatal and postnatal environmental tobacco smoke exposure and children's health. Children's exposure to tobacco constituents during fetal development and via environmental tobacco smoke (ETS) exposure is perhaps the most ubiquitous and hazardous of children's environmental exposures. A large literature links both prenatal maternal smoking and children's ETS exposure to decreased lung growth and increased rates of respiratory tract infections, otitis media, and childhood asthma, with the severity of these problems increasing with increased exposure. Sudden infant death syndrome, behavioral problems, neurocognitive decrements, and increased rates of adolescent smoking also are associated with such exposures. Studies of each of these problems suggest independent effects of both pre- and postnatal exposure for each, with the respiratory risk associated with parental smoking seeming to be greatest during fetal development and the first several years of life.. environmental tobacco smoke| children| prenatal| otitis media| asthma| sids|low-birth-weight| maternal cigarette-smoking| infant-death-syndrome| adolescent nicotine exposure| rat-brain regions| respiratory-tract illness| middle-ear disease| age 7 years| parental smoking| passive smoking.	APR 1-2004	environmental tobacco smoke| children| prenatal| otitis media| asthma| sids|low-birth-weight| maternal cigarette-smoking| infant-death-syndrome| adolescent nicotine exposure| rat-brain regions| respiratory-tract illness| middle-ear disease| age 7 years| parental smoking| passive smoking	DiFranza, JR; Aligne, CA; Weitzman, M	Prenatal and postnatal environmental tobacco smoke exposure and children's health		PEDIATRICS	environmental tobacco smoke; children; prenatal; otitis media; asthma; SIDS	LOW-BIRTH-WEIGHT; MATERNAL CIGARETTE-SMOKING; INFANT-DEATH-SYNDROME; ADOLESCENT NICOTINE EXPOSURE; RAT-BRAIN REGIONS; RESPIRATORY-TRACT ILLNESS; MIDDLE-EAR DISEASE; AGE 7 YEARS; PARENTAL SMOKING; PASSIVE SMOKING	Children's exposure to tobacco constituents during fetal development and via environmental tobacco smoke (ETS) exposure is perhaps the most ubiquitous and hazardous of children's environmental exposures. A large literature links both prenatal maternal smoking and children's ETS exposure to decreased lung growth and increased rates of respiratory tract infections, otitis media, and childhood asthma, with the severity of these problems increasing with increased exposure. Sudden infant death syndrome, behavioral problems, neurocognitive decrements, and increased rates of adolescent smoking also are associated with such exposures. Studies of each of these problems suggest independent effects of both pre- and postnatal exposure for each, with the respiratory risk associated with parental smoking seeming to be greatest during fetal development and the first several years of life.	173	415	2004	9		Pediatrics
Socioeconomic status and health: The potential role of environmental risk exposure. Among several viable explanations for the ubiquitous SES-health gradient is differential exposure to environmental risk. We document evidence of inverse relations between income and other indices of SES with environmental risk factors including hazardous wastes and other toxins, ambient and indoor air pollutants, water quality, ambient noise, residential crowding, housing quality, educational facilities, work environments, and neighborhood conditions. We then briefly over-view evidence that such exposures are inimical to health and well-being. We conclude with a discussion of the research and policy implications of environmental justice, arguing that a particularly salient feature of poverty for health consequences is exposure to multiple environmental risk factors.. environmental justice| income| socioeconomic status| poverty| environmental risk|home environments| young-children| cockroach allergen| class-inequality| carbon-monoxide| mental-health| united-states| air-pollution| social-class| quality.	2002	environmental justice| income| socioeconomic status| poverty| environmental risk|home environments| young-children| cockroach allergen| class-inequality| carbon-monoxide| mental-health| united-states| air-pollution| social-class| quality	Evans, GW; Kantrowitz, E	Socioeconomic status and health: The potential role of environmental risk exposure		ANNUAL REVIEW OF PUBLIC HEALTH	environmental justice; income; socioeconomic status; poverty; environmental risk	HOME ENVIRONMENTS; YOUNG-CHILDREN; COCKROACH ALLERGEN; CLASS-INEQUALITY; CARBON-MONOXIDE; MENTAL-HEALTH; UNITED-STATES; AIR-POLLUTION; SOCIAL-CLASS; QUALITY	Among several viable explanations for the ubiquitous SES-health gradient is differential exposure to environmental risk. We document evidence of inverse relations between income and other indices of SES with environmental risk factors including hazardous wastes and other toxins, ambient and indoor air pollutants, water quality, ambient noise, residential crowding, housing quality, educational facilities, work environments, and neighborhood conditions. We then briefly over-view evidence that such exposures are inimical to health and well-being. We conclude with a discussion of the research and policy implications of environmental justice, arguing that a particularly salient feature of poverty for health consequences is exposure to multiple environmental risk factors.	148	411	2002	29	10.1146/annurev.publhealth.23.112001.112349	Public, Environmental & Occupational Health
Sample size requirements for association studies of gene-gene interaction. In the study of complex diseases, it may be important to test hypotheses related to gene-gene (G x G) interaction. The success of such studies depends critically on obtaining adequate sample sizes. In this paper, the author investigates sample size requirements for studies of G x G interaction, focusing on four study designs: the matched-case-control design, the case-sibling design, the case-parent design, and the case-only design. All four designs provide an estimate of interaction on a multiplicative scale, which is used as a unifying theme in the comparison of sample size requirements. Across a variety of genetic models, the case-only and case-parent designs require fewer sampling units (cases and case-parent trios, respectively) than the case-control (pairs) or case-sibling (pairs) design. For example, the author describes an asthma study of two common recessive genes for which 270 matched case-control pairs would be required to detect a G x G interaction of moderate magnitude with 80% power. By comparison, the same study would require 319 case-sibling pairs but only 146 trios in the case-parent design or 116 cases in the case-only design. A software program that computes sample size for studies of G x G interaction and for studies of gene-environment (G x E) interaction is freely available (http://hydra.usc.edu/gxe).. association| case-control studies| genetics| interaction| research design| sample size|case-parent triads| case-control designs| environment interaction| linkage disequilibrium| power| tests| exposure| models.	MAR 1-2002	association| case-control studies| genetics| interaction| research design| sample size|case-parent triads| case-control designs| environment interaction| linkage disequilibrium| power| tests| exposure| models	Gauderman, WJ	Sample size requirements for association studies of gene-gene interaction		AMERICAN JOURNAL OF EPIDEMIOLOGY	association; case-control studies; genetics; interaction; research design; sample size	CASE-PARENT TRIADS; CASE-CONTROL DESIGNS; ENVIRONMENT INTERACTION; LINKAGE DISEQUILIBRIUM; POWER; TESTS; EXPOSURE; MODELS	In the study of complex diseases, it may be important to test hypotheses related to gene-gene (G x G) interaction. The success of such studies depends critically on obtaining adequate sample sizes. In this paper, the author investigates sample size requirements for studies of G x G interaction, focusing on four study designs: the matched-case-control design, the case-sibling design, the case-parent design, and the case-only design. All four designs provide an estimate of interaction on a multiplicative scale, which is used as a unifying theme in the comparison of sample size requirements. Across a variety of genetic models, the case-only and case-parent designs require fewer sampling units (cases and case-parent trios, respectively) than the case-control (pairs) or case-sibling (pairs) design. For example, the author describes an asthma study of two common recessive genes for which 270 matched case-control pairs would be required to detect a G x G interaction of moderate magnitude with 80% power. By comparison, the same study would require 319 case-sibling pairs but only 146 trios in the case-parent design or 116 cases in the case-only design. A software program that computes sample size for studies of G x G interaction and for studies of gene-environment (G x E) interaction is freely available (http://hydra.usc.edu/gxe).	42	409	2002	7	10.1093/aje/155.5.478	Public, Environmental & Occupational Health
Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Allergic diseases are caused by aberrant T-helper-2 immune responses in susceptible individuals. Both naturally occurring CD4(+)CD25(+) regulatory T cells and inducible populations of antigen-specific interleukin-10-secreting regulatory T cells inhibit these inappropriate immune responses in experimental models. This article discusses the evidence that regulatory T-cell function might be impaired in allergic and asthmatic disease and that certain therapeutic regimens might function, at least in part, to promote regulatory T-cell generation. Current research strategies seek to exploit these observations to improve the generation of allergen-specific regulatory T-cell populations with the potential to provide the safe and long-term alleviation of disease symptoms.. grass-pollen immunotherapy| induced airway hyperreactivity| immunological self-tolerance| colony-stimulating factor| transcription factor foxp3| growth-factor-beta| house-dust mite| fc-epsilon-ri| cytokine production| in-vivo.	APR-2005	grass-pollen immunotherapy| induced airway hyperreactivity| immunological self-tolerance| colony-stimulating factor| transcription factor foxp3| growth-factor-beta| house-dust mite| fc-epsilon-ri| cytokine production| in-vivo	Hawrylowicz, CM; O'Garra, A	Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma		NATURE REVIEWS IMMUNOLOGY		GRASS-POLLEN IMMUNOTHERAPY; INDUCED AIRWAY HYPERREACTIVITY; IMMUNOLOGICAL SELF-TOLERANCE; COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR FOXP3; GROWTH-FACTOR-BETA; HOUSE-DUST MITE; FC-EPSILON-RI; CYTOKINE PRODUCTION; IN-VIVO	Allergic diseases are caused by aberrant T-helper-2 immune responses in susceptible individuals. Both naturally occurring CD4(+)CD25(+) regulatory T cells and inducible populations of antigen-specific interleukin-10-secreting regulatory T cells inhibit these inappropriate immune responses in experimental models. This article discusses the evidence that regulatory T-cell function might be impaired in allergic and asthmatic disease and that certain therapeutic regimens might function, at least in part, to promote regulatory T-cell generation. Current research strategies seek to exploit these observations to improve the generation of allergen-specific regulatory T-cell populations with the potential to provide the safe and long-term alleviation of disease symptoms.	188	408	2005	13	10.1038/nri1589	Immunology
Reduced risk of hay fever and asthma among children of farmers. Background The prevalence of atopic diseases is on the rise. Traditional lifestyles may be associated with a reduced risk of atopy. Objective To test the hypothesis that children living on a farm have lower prevalences of atopic diseases. To identify differences in living conditions between farmers and other families which are associated with the development of atopic conditions. Design Cross-sectional survey among children entering school (aged 5-7 years). A written questionnaire including the ISAAC core questions and asking for exposures on a farm and elsewhere was administered to the parents. Setting: School health entry examination in two Bavarian districts with extensive farming activity. Subjects: 10 163 children. Main outcome measures The prevalence of doctor's diagnoses and symptoms of hay fever, asthma and eczema as assessed by parental report. Results Farmers' children had lower prevalences of hay fever (adjusted odds ratio = 0.52, 95% CI 0.28-0.99), asthma (0.65, 0.39-1.09), and wheeze (0.55, 0.36-0.86) than their peers not living in an agricultural environment. The reduction in risk was stronger for children whose families were running the farm on a full-time basis as compared with families with part-time farming activity. Among farmers' children increasing exposure to livestock was related to a decreasing prevalence of atopic diseases (aOR = 0.41, 95% CI 0.23-0.74). Conclusions Factors related to environmental influences on a farm such as increased exposure to bacterial compounds in stables where livestock is kept prevent the development of allergic disorders in children.. allergic rhinoconjunctivitis| childhood isaac| school-children| prevalence| symptoms| atopy| th1| sensitization| diseases| rhinitis.	FEB-2000	allergic rhinoconjunctivitis| childhood isaac| school-children| prevalence| symptoms| atopy| th1| sensitization| diseases| rhinitis	Von Ehrenstein, OS; Von Mutius, E; Illi, S; Baumann, L; Bohm, O; Von Kries, R	Reduced risk of hay fever and asthma among children of farmers		CLINICAL AND EXPERIMENTAL ALLERGY		ALLERGIC RHINOCONJUNCTIVITIS; CHILDHOOD ISAAC; SCHOOL-CHILDREN; PREVALENCE; SYMPTOMS; ATOPY; TH1; SENSITIZATION; DISEASES; RHINITIS	Background The prevalence of atopic diseases is on the rise. Traditional lifestyles may be associated with a reduced risk of atopy. Objective To test the hypothesis that children living on a farm have lower prevalences of atopic diseases. To identify differences in living conditions between farmers and other families which are associated with the development of atopic conditions. Design Cross-sectional survey among children entering school (aged 5-7 years). A written questionnaire including the ISAAC core questions and asking for exposures on a farm and elsewhere was administered to the parents. Setting: School health entry examination in two Bavarian districts with extensive farming activity. Subjects: 10 163 children. Main outcome measures The prevalence of doctor's diagnoses and symptoms of hay fever, asthma and eczema as assessed by parental report. Results Farmers' children had lower prevalences of hay fever (adjusted odds ratio = 0.52, 95% CI 0.28-0.99), asthma (0.65, 0.39-1.09), and wheeze (0.55, 0.36-0.86) than their peers not living in an agricultural environment. The reduction in risk was stronger for children whose families were running the farm on a full-time basis as compared with families with part-time farming activity. Among farmers' children increasing exposure to livestock was related to a decreasing prevalence of atopic diseases (aOR = 0.41, 95% CI 0.23-0.74). Conclusions Factors related to environmental influences on a farm such as increased exposure to bacterial compounds in stables where livestock is kept prevent the development of allergic disorders in children.	32	406	2000	7		Allergy; Immunology
Respiratory effects of exposure to diesel traffic in persons with asthma. Background: Air pollution from road traffic is a serious health hazard, and people with preexisting respiratory disease may be at increased risk. We investigated the effects of short-term exposure to diesel traffic in people with asthma in an urban, roadside environment. Methods: We recruited 60 adults with either mild or moderate asthma to participate in a randomized, crossover study. Each participant walked for 2 hours along a London street (Oxford Street) and, on a separate occasion, through a nearby park (Hyde Park). We performed detailed real-time exposure, physiological, and immunologic measurements. Results: Participants had significantly higher exposures to fine particles (<2.5 mu m in aerodynamic diameter), ultrafine particles, elemental carbon, and nitrogen dioxide on Oxford Street than in Hyde Park. Walking for 2 hours on Oxford Street induced asymptomatic but consistent reductions in the forced expiratory volume in 1 second (FEV1) (up to 6.1%) and forced vital capacity (FVC) (up to 5.4%) that were significantly larger than the reductions in FEV1 and FVC after exposure in Hyde Park (P=0.04 and P=0.01, respectively, for the overall effect of exposure, and P<0.005 at some time points). The effects were greater in subjects with moderate asthma than in those with mild asthma. These changes were accompanied by increases in biomarkers of neutrophilic inflammation (sputum myeloperoxidase, 4.24 ng per milliliter after exposure in Hyde Park vs. 24.5 ng per milliliter after exposure on Oxford Street; P=0.05) and airway acidification (maximum decrease in pH, 0.04% after exposure in Hyde Park and 1.9% after exposure on Oxford Street; P=0.003). The changes were associated most consistently with exposures to ultrafine particles and elemental carbon. Conclusions: Our observations serve as a demonstration and explanation of the epidemiologic evidence that associates the degree of traffic exposure with lung function in asthma.. ultrafine particles| airway inflammation| epithelial-cells| lung-function| exhaust| humans| health| pollution| symptoms.	DEC 6-2007	ultrafine particles| airway inflammation| epithelial-cells| lung-function| exhaust| humans| health| pollution| symptoms	McCreanor, J; Cullinan, P; Nieuwenhuijsen, MJ; Stewart-Evans, J; Malliarou, E; Jarup, L; Harrington, R; Svartengren, M; Han, I; Ohman-Strickland, P; Chung, KF; Zhang, JF	Respiratory effects of exposure to diesel traffic in persons with asthma		NEW ENGLAND JOURNAL OF MEDICINE		ULTRAFINE PARTICLES; AIRWAY INFLAMMATION; EPITHELIAL-CELLS; LUNG-FUNCTION; EXHAUST; HUMANS; HEALTH; POLLUTION; SYMPTOMS	Background: Air pollution from road traffic is a serious health hazard, and people with preexisting respiratory disease may be at increased risk. We investigated the effects of short-term exposure to diesel traffic in people with asthma in an urban, roadside environment. Methods: We recruited 60 adults with either mild or moderate asthma to participate in a randomized, crossover study. Each participant walked for 2 hours along a London street (Oxford Street) and, on a separate occasion, through a nearby park (Hyde Park). We performed detailed real-time exposure, physiological, and immunologic measurements. Results: Participants had significantly higher exposures to fine particles (<2.5 mu m in aerodynamic diameter), ultrafine particles, elemental carbon, and nitrogen dioxide on Oxford Street than in Hyde Park. Walking for 2 hours on Oxford Street induced asymptomatic but consistent reductions in the forced expiratory volume in 1 second (FEV1) (up to 6.1%) and forced vital capacity (FVC) (up to 5.4%) that were significantly larger than the reductions in FEV1 and FVC after exposure in Hyde Park (P=0.04 and P=0.01, respectively, for the overall effect of exposure, and P<0.005 at some time points). The effects were greater in subjects with moderate asthma than in those with mild asthma. These changes were accompanied by increases in biomarkers of neutrophilic inflammation (sputum myeloperoxidase, 4.24 ng per milliliter after exposure in Hyde Park vs. 24.5 ng per milliliter after exposure on Oxford Street; P=0.05) and airway acidification (maximum decrease in pH, 0.04% after exposure in Hyde Park and 1.9% after exposure on Oxford Street; P=0.003). The changes were associated most consistently with exposures to ultrafine particles and elemental carbon. Conclusions: Our observations serve as a demonstration and explanation of the epidemiologic evidence that associates the degree of traffic exposure with lung function in asthma.	28	405	2007	11	10.1056/NEJMoa071535	General & Internal Medicine
What are the sources of exposure to eight frequently used phthalic acid esters in Europeans?. Phthalic acid esters (phthalates) are used as plasticizers in numerous consumer products, commodities, and building materials. Consequently, phthalates are found in human residential and occupational environments in high concentrations, both in air and in dust. Phthalates are also ubiquitous food and environmental contaminants. An increasing number of studies sampling human urine reveal the ubiquitous phthalate exposure of consumers in industrialized countries. At the same time, recent toxicological studies have demonstrated the potential of the most important phthalates to disturb the human hormonal system and human sexual development and reproduction. Additionally, phthalates are suspected to trigger asthma and dermal diseases in children. To find the important sources of phthalates in Europeans, a scenario-based approach is applied here. Scenarios representing realistic exposure situations are generated to calculate the age-specific range in daily consumer exposure to eight phthalates. The scenarios demonstrate that exposure of infant and adult consumers is caused by different sources in many cases. Infant consumers experience significantly higher daily exposure to phthalates in relation to their body weight than older consumers. The use of consumer products and different indoor sources dominate the exposure to dimethyl, diethyl, benzylbutyl, diisononyl, and diisodecyl phthalates, whereas food has a major influence on the exposure to diisobutyl, dibutyl, and di-2-ethylhexyl phthalates. The scenario-based approach chosen in the present study provides a link between the knowledge on emission sources of phthalates and the concentrations of phthalate metabolites found in human urine.. consumer exposure| consumer products| exposure modeling| exposure pathways| phthalates| plasticizers|expert panel report| n-butyl phthalate| male reproductive development| nursery-school children| deuterium-labeled dehp| di-isononyl phthalate| in-house dust| developmental toxicity| ntp center| di(2-ethylhexyl)phthalate dehp.	JUN-2006	consumer exposure| consumer products| exposure modeling| exposure pathways| phthalates| plasticizers|expert panel report| n-butyl phthalate| male reproductive development| nursery-school children| deuterium-labeled dehp| di-isononyl phthalate| in-house dust| developmental toxicity| ntp center| di(2-ethylhexyl)phthalate dehp	Wormuth, M; Scheringer, M; Vollenweider, M; Hungerbuhler, K	What are the sources of exposure to eight frequently used phthalic acid esters in Europeans?		RISK ANALYSIS	consumer exposure; consumer products; exposure modeling; exposure pathways; phthalates; plasticizers	EXPERT PANEL REPORT; N-BUTYL PHTHALATE; MALE REPRODUCTIVE DEVELOPMENT; NURSERY-SCHOOL CHILDREN; DEUTERIUM-LABELED DEHP; DI-ISONONYL PHTHALATE; IN-HOUSE DUST; DEVELOPMENTAL TOXICITY; NTP CENTER; DI(2-ETHYLHEXYL)PHTHALATE DEHP	Phthalic acid esters (phthalates) are used as plasticizers in numerous consumer products, commodities, and building materials. Consequently, phthalates are found in human residential and occupational environments in high concentrations, both in air and in dust. Phthalates are also ubiquitous food and environmental contaminants. An increasing number of studies sampling human urine reveal the ubiquitous phthalate exposure of consumers in industrialized countries. At the same time, recent toxicological studies have demonstrated the potential of the most important phthalates to disturb the human hormonal system and human sexual development and reproduction. Additionally, phthalates are suspected to trigger asthma and dermal diseases in children. To find the important sources of phthalates in Europeans, a scenario-based approach is applied here. Scenarios representing realistic exposure situations are generated to calculate the age-specific range in daily consumer exposure to eight phthalates. The scenarios demonstrate that exposure of infant and adult consumers is caused by different sources in many cases. Infant consumers experience significantly higher daily exposure to phthalates in relation to their body weight than older consumers. The use of consumer products and different indoor sources dominate the exposure to dimethyl, diethyl, benzylbutyl, diisononyl, and diisodecyl phthalates, whereas food has a major influence on the exposure to diisobutyl, dibutyl, and di-2-ethylhexyl phthalates. The scenario-based approach chosen in the present study provides a link between the knowledge on emission sources of phthalates and the concentrations of phthalate metabolites found in human urine.	118	396	2006	22	10.1111/j.1539-6924.2006.00770.x	Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences
Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase-and cathepsin-dependent emphysema. Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop significant COPD, and patients with asthma or asthma-like airway hyperresponsiveness or eosinophilia experience accelerated loss of lung function after cigarette smoke exposure. Pulmonary inflammation is a characteristic feature of lungs from patients with COPD. Surprisingly, the mediators of this inflammation and their contributions to the pathogenesis and varied natural history of COPD are not well defined. Here we show that IL-13, a critical cytokine in asthma, causes emphysema with enhanced lung volumes and compliance, mucus metaplasia, and inflammation, when inducibly overexpressed in the adult murine lung. MMP-2, -9, -12, -13, and -14 and cathepsins B, S, L, H, and K were induced by IL-13 in this setting. Zn addition, treatment with MMP or cysteine proteinase antagonists significantly decreased the emphysema and inflammation, but not the mucus in these animals. These studies demonstrate that IL-13 is a potent stimulator of MMP and cathepsin-based proteolytic pathways in the lung. They also demonstrate that IL-13 causes emphysema via a MMP- and cathepsin-dependent mechanism(s) and highlight common mechanisms that may underlie COPD and asthma.. obstructive pulmonary-disease| bronchoalveolar lavage fluid| chronic-bronchitis| cysteine proteinases| airway hyperresponsiveness| alveolar macrophages| t-lymphocytes| responsiveness| smokers| cells.	NOV-2000	obstructive pulmonary-disease| bronchoalveolar lavage fluid| chronic-bronchitis| cysteine proteinases| airway hyperresponsiveness| alveolar macrophages| t-lymphocytes| responsiveness| smokers| cells	Zheng, T; Zhu, Z; Wang, ZD; Homer, RJ; Ma, B; Riese, RJ; Chapman, HA; Shapiro, SD; Elias, JA	Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase-and cathepsin-dependent emphysema		JOURNAL OF CLINICAL INVESTIGATION		OBSTRUCTIVE PULMONARY-DISEASE; BRONCHOALVEOLAR LAVAGE FLUID; CHRONIC-BRONCHITIS; CYSTEINE PROTEINASES; AIRWAY HYPERRESPONSIVENESS; ALVEOLAR MACROPHAGES; T-LYMPHOCYTES; RESPONSIVENESS; SMOKERS; CELLS	Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop significant COPD, and patients with asthma or asthma-like airway hyperresponsiveness or eosinophilia experience accelerated loss of lung function after cigarette smoke exposure. Pulmonary inflammation is a characteristic feature of lungs from patients with COPD. Surprisingly, the mediators of this inflammation and their contributions to the pathogenesis and varied natural history of COPD are not well defined. Here we show that IL-13, a critical cytokine in asthma, causes emphysema with enhanced lung volumes and compliance, mucus metaplasia, and inflammation, when inducibly overexpressed in the adult murine lung. MMP-2, -9, -12, -13, and -14 and cathepsins B, S, L, H, and K were induced by IL-13 in this setting. Zn addition, treatment with MMP or cysteine proteinase antagonists significantly decreased the emphysema and inflammation, but not the mucus in these animals. These studies demonstrate that IL-13 is a potent stimulator of MMP and cathepsin-based proteolytic pathways in the lung. They also demonstrate that IL-13 causes emphysema via a MMP- and cathepsin-dependent mechanism(s) and highlight common mechanisms that may underlie COPD and asthma.	53	393	2000	13	10.1172/JCI10458	Research & Experimental Medicine
Asthma in exercising children exposed to ozone: a cohort study. Background Little is known about the effect of exposure to air pollution during exercise or time spent outdoors on the development of asthma. We investigated the relation between newly-diagnosed asthma and team sports in a cohort of children exposed to different concentrations and mixtures of air pollutants. Methods 3535 children with no history of asthma were recruited from schools in 12 communities in southern California and were followed up for up to 5 years. 265 children reported a new diagnosis of asthma during follow-up. We assessed risk of asthma in children playing team sports at study entry in six communities with high daytime ozone concentrations, six with lower concentrations, and in communities with high or low concentrations of nitrogen dioxide, particulate matter, and inorganic-acid vapour. Findings In communities with high ozone concentrations, the relative risk of developing asthma in children playing three or more sports was 3.3 (95% CI 1.9-5.8), compared with children playing no sports. Sports had no effect in areas of low ozone concentration (0.8, 0.4-1.6). Time spent outside was associated with a higher incidence of asthma in areas of high ozone (1.4, 1.0-2.1), but not in areas of low ozone. Exposure to pollutants other than ozone did not alter the effect of team sports. Interpretation Incidence of new diagnoses of asthma is associated with heavy exercise in communities with high concentrations of ozone, thus, air pollution and outdoor exercise could contribute to the development of asthma in children.. southern california children| air-pollution| bronchial responsiveness| childhood asthma| school children| prevalence| pollutants| association| symptoms| taiwan.	FEB 2-2002	southern california children| air-pollution| bronchial responsiveness| childhood asthma| school children| prevalence| pollutants| association| symptoms| taiwan	McConnell, R; Berhane, K; Gilliland, F; London, SJ; Islam, T; Gauderman, WJ; Avol, E; Margolis, HG; Peters, JM	Asthma in exercising children exposed to ozone: a cohort study		LANCET		SOUTHERN CALIFORNIA CHILDREN; AIR-POLLUTION; BRONCHIAL RESPONSIVENESS; CHILDHOOD ASTHMA; SCHOOL CHILDREN; PREVALENCE; POLLUTANTS; ASSOCIATION; SYMPTOMS; TAIWAN	Background Little is known about the effect of exposure to air pollution during exercise or time spent outdoors on the development of asthma. We investigated the relation between newly-diagnosed asthma and team sports in a cohort of children exposed to different concentrations and mixtures of air pollutants. Methods 3535 children with no history of asthma were recruited from schools in 12 communities in southern California and were followed up for up to 5 years. 265 children reported a new diagnosis of asthma during follow-up. We assessed risk of asthma in children playing team sports at study entry in six communities with high daytime ozone concentrations, six with lower concentrations, and in communities with high or low concentrations of nitrogen dioxide, particulate matter, and inorganic-acid vapour. Findings In communities with high ozone concentrations, the relative risk of developing asthma in children playing three or more sports was 3.3 (95% CI 1.9-5.8), compared with children playing no sports. Sports had no effect in areas of low ozone concentration (0.8, 0.4-1.6). Time spent outside was associated with a higher incidence of asthma in areas of high ozone (1.4, 1.0-2.1), but not in areas of low ozone. Exposure to pollutants other than ozone did not alter the effect of team sports. Interpretation Incidence of new diagnoses of asthma is associated with heavy exercise in communities with high concentrations of ozone, thus, air pollution and outdoor exercise could contribute to the development of asthma in children.	32	391	2002	6	10.1016/S0140-6736(02)07597-9	General & Internal Medicine
Chronic obstructive pulmonary disease in non-smokers. Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Tobacco smoking is established as a major risk factor, but emerging evidence suggests that other risk factors are important, especially in developing countries. An estimated 25-45% of patients with COPD have never smoked; the burden of non-smoking COPD is therefore much higher than previously believed. About 3 billion people, half the worldwide population, are exposed to smoke from biomass fuel compared with 1.01 billion people who smoke tobacco, which suggests that exposure to biomass smoke might be the biggest risk factor for COPD globally. We review the evidence for the association of COPD with biomass fuel, occupational exposure to dusts and gases, history of pulmonary tuberculosis, chronic asthma, respiratory-tract infections during childhood, outdoor air pollution, and poor socioeconomic status.. indoor air-pollution| nutrition examination survey| chronic respiratory-disease| chronic-bronchitis| lung-function| biomass smoke| occupational exposures| socioeconomic-status| developing-countries| ventilatory function.	AUG-SEP-2009	indoor air-pollution| nutrition examination survey| chronic respiratory-disease| chronic-bronchitis| lung-function| biomass smoke| occupational exposures| socioeconomic-status| developing-countries| ventilatory function	Salvi, SS; Barnes, PJ	Chronic obstructive pulmonary disease in non-smokers		LANCET		INDOOR AIR-POLLUTION; NUTRITION EXAMINATION SURVEY; CHRONIC RESPIRATORY-DISEASE; CHRONIC-BRONCHITIS; LUNG-FUNCTION; BIOMASS SMOKE; OCCUPATIONAL EXPOSURES; SOCIOECONOMIC-STATUS; DEVELOPING-COUNTRIES; VENTILATORY FUNCTION	Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Tobacco smoking is established as a major risk factor, but emerging evidence suggests that other risk factors are important, especially in developing countries. An estimated 25-45% of patients with COPD have never smoked; the burden of non-smoking COPD is therefore much higher than previously believed. About 3 billion people, half the worldwide population, are exposed to smoke from biomass fuel compared with 1.01 billion people who smoke tobacco, which suggests that exposure to biomass smoke might be the biggest risk factor for COPD globally. We review the evidence for the association of COPD with biomass fuel, occupational exposure to dusts and gases, history of pulmonary tuberculosis, chronic asthma, respiratory-tract infections during childhood, outdoor air pollution, and poor socioeconomic status.	107	390	2009	11		General & Internal Medicine
Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multi pie-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.. asthma| episodic viral wheeze| inhaled corticosteroids| montelukast| multiple-trigger wheeze|exhaled nitric-oxide| respiratory syncytial virus| budesonide inhalation suspension| placebo-controlled trial| leukotriene receptor antagonist| inhaled fluticasone propionate| randomized controlled-trial| young asthmatic-children| episodic viral wheeze| prospective follow-up.	OCT-2008	asthma| episodic viral wheeze| inhaled corticosteroids| montelukast| multiple-trigger wheeze|exhaled nitric-oxide| respiratory syncytial virus| budesonide inhalation suspension| placebo-controlled trial| leukotriene receptor antagonist| inhaled fluticasone propionate| randomized controlled-trial| young asthmatic-children| episodic viral wheeze| prospective follow-up	Brand, PLP; Baraldi, E; Bisgaard, H; Boner, AL; Castro-Rodriguez, JA; Custovic, A; de Blic, J; de Jongste, JC; Eber, E; Everard, ML; Frey, U; Gappa, M; Garcia-Marcos, L; Grigg, J; Lenney, W; Le Souef, P; McKenzie, S; Merkus, PJFM; Midulla, F; Paton, JY; Piacentini, G; Pohunek, P; Rossi, GA; Seddon, P; Silverman, M; Sly, PD; Stick, S; Valiulis, A; van Aalderen, WMC; Wildhaber, JH; Wennergren, G; Wilson, N; Zivkovic, Z; Bush, A	Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach		EUROPEAN RESPIRATORY JOURNAL	asthma; episodic viral wheeze; inhaled corticosteroids; montelukast; multiple-trigger wheeze	EXHALED NITRIC-OXIDE; RESPIRATORY SYNCYTIAL VIRUS; BUDESONIDE INHALATION SUSPENSION; PLACEBO-CONTROLLED TRIAL; LEUKOTRIENE RECEPTOR ANTAGONIST; INHALED FLUTICASONE PROPIONATE; RANDOMIZED CONTROLLED-TRIAL; YOUNG ASTHMATIC-CHILDREN; EPISODIC VIRAL WHEEZE; PROSPECTIVE FOLLOW-UP	There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multi pie-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.	142	387	2008	15	10.1183/09031936.00002108	Respiratory System
Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study. Background Reduced lung function is a feature of chronic asthma, which becomes apparent at school age. Unknown factors between birth and school age determine the progressive loss of pulmonary function in children with persistent asthma. We investigated the role of allergic sensitisation and allergen exposure early in life. Methods The German Multicentre Allergy Study followed 1314 children from birth to 13 years of age. We regularly interviewed parents about their child's asthma and measured IgE levels. Allergen exposure was assessed at age 6 months, 18 months, and at 3, 4, and 5 years; lung function was assessed at 7, 10, and 13 years; post-bronchodilator response at 10 and 13 years; and a bronchial histamine challenge was done at 7 years. Results 90% of children with wheeze but no atopy lost their symptoms at school age and retained normal lung function at puberty. By contrast, sensitisation to perennial allergens (eg, house dust mite, cat and dog hair) developing in the first 3 years of life was associated with a loss of lung function at school age. Concomitant exposure to high levels of perennial allergens early in life aggravated this process: forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio was 87.4 (SD 7.4) for those sensitised and with high exposure compared with 92.6 (6.0) for those not sensitised, p<0.0001; and maximal expiratory flow at 50% (MEF50) 86.4 (25.1) for sensitised and with high exposure compared with 101.5 (23.2; p=0.0031) for those not sensitised. Such exposure also enhanced the development of airway hyper-responsiveness in sensitised children with wheeze. Sensitisation and exposure later in life had much weaker effects and sensitisation to seasonal allergens did not play a part. Interpretation The chronic course of asthma characterised by airway hyper-responsiveness and impairment of lung function at school age is determined by continuing allergic airway inflammation beginning in the first 3 years of life. However, children with a non-atopic wheezing phenotype lose their symptoms over school age and retain normal lung function at puberty.. house-dust mite| age 3 years| childhood asthma| lung-function| inhaled corticosteroids| preschool-children| exposure| prevalence| symptoms| germany.	AUG-SEP-2006	house-dust mite| age 3 years| childhood asthma| lung-function| inhaled corticosteroids| preschool-children| exposure| prevalence| symptoms| germany	Illi, S; von Mutius, E; Lau, S; Niggemann, B; Gruber, C; Wahn, U	Perennial allergen sensitisation early in life and chronic asthma in children: a birth cohort study		LANCET		HOUSE-DUST MITE; AGE 3 YEARS; CHILDHOOD ASTHMA; LUNG-FUNCTION; INHALED CORTICOSTEROIDS; PRESCHOOL-CHILDREN; EXPOSURE; PREVALENCE; SYMPTOMS; GERMANY	Background Reduced lung function is a feature of chronic asthma, which becomes apparent at school age. Unknown factors between birth and school age determine the progressive loss of pulmonary function in children with persistent asthma. We investigated the role of allergic sensitisation and allergen exposure early in life. Methods The German Multicentre Allergy Study followed 1314 children from birth to 13 years of age. We regularly interviewed parents about their child's asthma and measured IgE levels. Allergen exposure was assessed at age 6 months, 18 months, and at 3, 4, and 5 years; lung function was assessed at 7, 10, and 13 years; post-bronchodilator response at 10 and 13 years; and a bronchial histamine challenge was done at 7 years. Results 90% of children with wheeze but no atopy lost their symptoms at school age and retained normal lung function at puberty. By contrast, sensitisation to perennial allergens (eg, house dust mite, cat and dog hair) developing in the first 3 years of life was associated with a loss of lung function at school age. Concomitant exposure to high levels of perennial allergens early in life aggravated this process: forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio was 87.4 (SD 7.4) for those sensitised and with high exposure compared with 92.6 (6.0) for those not sensitised, p<0.0001; and maximal expiratory flow at 50% (MEF50) 86.4 (25.1) for sensitised and with high exposure compared with 101.5 (23.2; p=0.0031) for those not sensitised. Such exposure also enhanced the development of airway hyper-responsiveness in sensitised children with wheeze. Sensitisation and exposure later in life had much weaker effects and sensitisation to seasonal allergens did not play a part. Interpretation The chronic course of asthma characterised by airway hyper-responsiveness and impairment of lung function at school age is determined by continuing allergic airway inflammation beginning in the first 3 years of life. However, children with a non-atopic wheezing phenotype lose their symptoms over school age and retain normal lung function at puberty.	28	384	2006	8	10.1016/S0140-6736(06)69286-6	General & Internal Medicine
Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma. The mechanisms contributing to airway wall remodeling in asthma are under investigation to identify appropriate therapeutic targets. Bronchial myofibroblasts would represent an important target because they play a crucial role in the genesis of subepithelial fibrosis, a characteristic feature of the remodeling process, but their origin is poorly understood. We hypothesized that they originate from fibrocytes, circulating cells with the unique characteristic of expressing the hemopoietic stem cell Ag CD34 and collagen I. In this study we show that allergen exposure induces the accumulation of fibrocyte-like cells in the bronchial mucosa of patients with allergic asthma. These cells are CD34-positive; express collagen I and a-smooth muscle actin, a marker of myofibroblasts; and localize to areas of collagen deposition below the epithelium. By tracking labeled circulating fibrocytes in a mouse model of allergic asthma, we provide evidence that fibrocytes are indeed recruited into the bronchial tissue following allergen exposure and differentiate into myofibroblasts. We also show that human circulating fibrocytes acquire the myofibroblast phenotype under in vitro stimulation with fibrogenic cytokines that are produced in exaggerated quantities in asthmatic airways. These results indicate that circulating fibrocytes may function as myofibroblast precursors and may contribute to the genesis of subepithelial fibrosis in asthma.. bronchoalveolar lavage fluid| human-lung fibroblasts| epithelial-cells| subepithelial fibrosis| in-situ| expression| airway| inflammation| endothelin-1| obstruction.	JUL 1-2003	bronchoalveolar lavage fluid| human-lung fibroblasts| epithelial-cells| subepithelial fibrosis| in-situ| expression| airway| inflammation| endothelin-1| obstruction	Schmidt, M; Sun, G; Stacey, MA; Mori, L; Mattoli, S	Identification of circulating fibrocytes as precursors of bronchial myofibroblasts in asthma		JOURNAL OF IMMUNOLOGY		BRONCHOALVEOLAR LAVAGE FLUID; HUMAN-LUNG FIBROBLASTS; EPITHELIAL-CELLS; SUBEPITHELIAL FIBROSIS; IN-SITU; EXPRESSION; AIRWAY; INFLAMMATION; ENDOTHELIN-1; OBSTRUCTION	The mechanisms contributing to airway wall remodeling in asthma are under investigation to identify appropriate therapeutic targets. Bronchial myofibroblasts would represent an important target because they play a crucial role in the genesis of subepithelial fibrosis, a characteristic feature of the remodeling process, but their origin is poorly understood. We hypothesized that they originate from fibrocytes, circulating cells with the unique characteristic of expressing the hemopoietic stem cell Ag CD34 and collagen I. In this study we show that allergen exposure induces the accumulation of fibrocyte-like cells in the bronchial mucosa of patients with allergic asthma. These cells are CD34-positive; express collagen I and a-smooth muscle actin, a marker of myofibroblasts; and localize to areas of collagen deposition below the epithelium. By tracking labeled circulating fibrocytes in a mouse model of allergic asthma, we provide evidence that fibrocytes are indeed recruited into the bronchial tissue following allergen exposure and differentiate into myofibroblasts. We also show that human circulating fibrocytes acquire the myofibroblast phenotype under in vitro stimulation with fibrogenic cytokines that are produced in exaggerated quantities in asthmatic airways. These results indicate that circulating fibrocytes may function as myofibroblast precursors and may contribute to the genesis of subepithelial fibrosis in asthma.	46	384	2003	10		Immunology
Acute effects of particulate air pollution on respiratory admissions - Results from APHEA 2 project. The APHEA 2 project investigated short-term health effects of particles in eight European cities. In each city associations between particles with an aerodynamic diameter of less than 10 mum (PM10) and black smoke and daily counts of emergency hospital admissions for asthma (0-14 and 15-64 yr), chronic obstructive pulmonary disease (COPD), and all-respiratory disease (65+ yr) controlling for environmental factors and temporal patterns were investigated. Summary PM10 effect estimates (percentage change in mean number of daily admissions per 10 mug/m(3) increase) were asthma (0-14 yr) 1.2% (95% Cl: 0.2, 2.3), asthma (15-64 yr) 1.1% (0.3, 1.8), and COPD plus asthma and all-respiratory (65+ yr) 1.0% (0.4, 1.5) and 0.9% (0.6, 1.3). The combined estimates for Black Smoke tended to be smaller and less precisely estimated than for PM10. Variability in the sizes of the PM10 effect estimates between cities was also investigated. In the 65+ groups PM10 estimates were positively associated with annual mean concentrations of ozone In the cities. For asthma admissions (0-14 yr) a number of city-specific factors, including smoking prevalence, explained some of their variability. This study confirms that particle concentrations in European cities are positively associated with increased numbers of admissions for respiratory diseases and that some of the variation in PM10 effect estimates between cities can be explained by city characteristics.. particles| respiratory admissions| heterogeneity| aphea 2|time-series data| hospital admissions| european cities| health| asthma| disease| ozone| urban.	NOV 15-2001	particles| respiratory admissions| heterogeneity| aphea 2|time-series data| hospital admissions| european cities| health| asthma| disease| ozone| urban	Atkinson, RW; Anderson, HR; Sunyer, J; Ayres, J; Baccini, M; Vonk, JM; Boumghar, A; Forastiere, F; Forsberg, B; Touloumi, G; Schwartz, J; Katsouyanni, K	Acute effects of particulate air pollution on respiratory admissions - Results from APHEA 2 project		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	particles; respiratory admissions; heterogeneity; APHEA 2	TIME-SERIES DATA; HOSPITAL ADMISSIONS; EUROPEAN CITIES; HEALTH; ASTHMA; DISEASE; OZONE; URBAN	The APHEA 2 project investigated short-term health effects of particles in eight European cities. In each city associations between particles with an aerodynamic diameter of less than 10 mum (PM10) and black smoke and daily counts of emergency hospital admissions for asthma (0-14 and 15-64 yr), chronic obstructive pulmonary disease (COPD), and all-respiratory disease (65+ yr) controlling for environmental factors and temporal patterns were investigated. Summary PM10 effect estimates (percentage change in mean number of daily admissions per 10 mug/m(3) increase) were asthma (0-14 yr) 1.2% (95% Cl: 0.2, 2.3), asthma (15-64 yr) 1.1% (0.3, 1.8), and COPD plus asthma and all-respiratory (65+ yr) 1.0% (0.4, 1.5) and 0.9% (0.6, 1.3). The combined estimates for Black Smoke tended to be smaller and less precisely estimated than for PM10. Variability in the sizes of the PM10 effect estimates between cities was also investigated. In the 65+ groups PM10 estimates were positively associated with annual mean concentrations of ozone In the cities. For asthma admissions (0-14 yr) a number of city-specific factors, including smoking prevalence, explained some of their variability. This study confirms that particle concentrations in European cities are positively associated with increased numbers of admissions for respiratory diseases and that some of the variation in PM10 effect estimates between cities can be explained by city characteristics.	22	382	2001	7		General & Internal Medicine; Respiratory System
"Dampness in buildings and health - Nordic interdisciplinary review of the scientific evidence on associations between exposure to ""dampness"" in buildings and health effects (NORDDAMP). Several epidemiological investigations concerning indoor environments have indicated that ""dampness"" in buildings is associated to health effects such as respiratory symptoms, asthma and allergy The aim of the present interdisciplinary review is to evaluate this association as shown in the epidemiological literature. A literature search identified 590 peer-reviewed articles of which 61 have been the foundation for this review. The review shows that ""dampness"" in buildings appears to increase the risk for health effects in the airways, such as cough, wheeze and asthma. Relative risks are in the range of OR 1.4-2.2. There also seems to be an association between ""dampness"" and other symptoms Such as tiredness, headache and airways infections. It is concluded that the evidence for a causal association between ""dampness"" and health effects is strong. However, the mechanisms are unknown. Several definitions of dampness have been used in the studies, but all seems to be associated with health problems. Sensitisation to mites may be one but obviously not the only mechanism. Even if the mechanisms are unknown, there is sufficient evidence to take preventive measures against dampness in buildings.. review| dampness| exposure| health effects| allergy| asthma|house-dust mites| day-care-centers| childhood respiratory symptoms| environmental risk-factors| volatile organic-compounds| primary-school children| reported home dampness| indoor air-quality| residential characteristics| subtropical climate."	JUN-2001	review| dampness| exposure| health effects| allergy| asthma|house-dust mites| day-care-centers| childhood respiratory symptoms| environmental risk-factors| volatile organic-compounds| primary-school children| reported home dampness| indoor air-quality| residential characteristics| subtropical climate	Bornehag, CG; Blomquist, G; Gyntelberg, F; Jarvholm, B; Malmberg, P; Nordvall, L; Nielsen, A; Pershagen, G; Sundell, J	"Dampness in buildings and health - Nordic interdisciplinary review of the scientific evidence on associations between exposure to ""dampness"" in buildings and health effects (NORDDAMP)"		INDOOR AIR-INTERNATIONAL JOURNAL OF INDOOR AIR QUALITY AND CLIMATE	review; dampness; exposure; health effects; allergy; asthma	HOUSE-DUST MITES; DAY-CARE-CENTERS; CHILDHOOD RESPIRATORY SYMPTOMS; ENVIRONMENTAL RISK-FACTORS; VOLATILE ORGANIC-COMPOUNDS; PRIMARY-SCHOOL CHILDREN; REPORTED HOME DAMPNESS; INDOOR AIR-QUALITY; RESIDENTIAL CHARACTERISTICS; SUBTROPICAL CLIMATE	"Several epidemiological investigations concerning indoor environments have indicated that ""dampness"" in buildings is associated to health effects such as respiratory symptoms, asthma and allergy The aim of the present interdisciplinary review is to evaluate this association as shown in the epidemiological literature. A literature search identified 590 peer-reviewed articles of which 61 have been the foundation for this review. The review shows that ""dampness"" in buildings appears to increase the risk for health effects in the airways, such as cough, wheeze and asthma. Relative risks are in the range of OR 1.4-2.2. There also seems to be an association between ""dampness"" and other symptoms Such as tiredness, headache and airways infections. It is concluded that the evidence for a causal association between ""dampness"" and health effects is strong. However, the mechanisms are unknown. Several definitions of dampness have been used in the studies, but all seems to be associated with health problems. Sensitisation to mites may be one but obviously not the only mechanism. Even if the mechanisms are unknown, there is sufficient evidence to take preventive measures against dampness in buildings."	119	382	2001	15		Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Aeroallergy results from maladaptive immune responses to ubiquitous, otherwise innocuous environmental proteins(1). Although the proteins targeted by aeroallergic responses represent a tiny fraction of the airborne proteins humans are exposed to, allergenicity is a quite public phenomenon - the same proteins typically behave as aeroallergens across the human population. Why particular proteins tend to act as allergens in susceptible hosts is a fundamental mechanistic question that remains largely unanswered. The main house- dust- mite allergen, Der p 2, has structural homology with MD- 2 ( also known as LY96), the lipopolysaccharide ( LPS)- binding component of the Toll- like receptor ( TLR) 4 signalling complex(2-4). Here we show that Der p 2 also has functional homology, facilitating signalling through direct interactions with the TLR4 complex, and reconstituting LPS- driven TLR4 signalling in the absence of MD- 2. Mirroring this, airway sensitization and challenge with Der p 2 led to experimental allergic asthma in wild type and MD- 2- deficient, but not TLR4- deficient, mice. Our results indicate that Der p 2 tends to be targeted by adaptive immune responses because of its auto-adjuvant properties. The fact that other members of the MD- 2- like lipid- binding family are allergens, and that most defined major allergens are thought to be lipid- binding proteins(5), suggests that intrinsic adjuvant activity by such proteins and their accompanying lipid cargo may have some generality as a mechanism underlying the phenomenon of allergenicity.. tlr4-md-2 complex| crystal-structure| allergic disease| cell activation| endotoxin| md-2| asthma| lipopolysaccharide| responses| exposure.	JAN 29-2009	tlr4-md-2 complex| crystal-structure| allergic disease| cell activation| endotoxin| md-2| asthma| lipopolysaccharide| responses| exposure	Trompette, A; Divanovic, S; Visintin, A; Blanchard, C; Hegde, RS; Madan, R; Thorne, PS; Wills-Karp, M; Gioannini, TL; Weiss, JP; Karp, CL	Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein		NATURE		TLR4-MD-2 COMPLEX; CRYSTAL-STRUCTURE; ALLERGIC DISEASE; CELL ACTIVATION; ENDOTOXIN; MD-2; ASTHMA; LIPOPOLYSACCHARIDE; RESPONSES; EXPOSURE	Aeroallergy results from maladaptive immune responses to ubiquitous, otherwise innocuous environmental proteins(1). Although the proteins targeted by aeroallergic responses represent a tiny fraction of the airborne proteins humans are exposed to, allergenicity is a quite public phenomenon - the same proteins typically behave as aeroallergens across the human population. Why particular proteins tend to act as allergens in susceptible hosts is a fundamental mechanistic question that remains largely unanswered. The main house- dust- mite allergen, Der p 2, has structural homology with MD- 2 ( also known as LY96), the lipopolysaccharide ( LPS)- binding component of the Toll- like receptor ( TLR) 4 signalling complex(2-4). Here we show that Der p 2 also has functional homology, facilitating signalling through direct interactions with the TLR4 complex, and reconstituting LPS- driven TLR4 signalling in the absence of MD- 2. Mirroring this, airway sensitization and challenge with Der p 2 led to experimental allergic asthma in wild type and MD- 2- deficient, but not TLR4- deficient, mice. Our results indicate that Der p 2 tends to be targeted by adaptive immune responses because of its auto-adjuvant properties. The fact that other members of the MD- 2- like lipid- binding family are allergens, and that most defined major allergens are thought to be lipid- binding proteins(5), suggests that intrinsic adjuvant activity by such proteins and their accompanying lipid cargo may have some generality as a mechanism underlying the phenomenon of allergenicity.	30	381	2009	5	10.1038/nature07548	Science & Technology - Other Topics
Rhinovirus illnesses during infancy predict subsequent childhood wheezing. Background: The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/ or allergic diseases in early childhood is not established. Objective: To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. Methods: By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. Results: Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR] = 2.1), older siblings (OR = 2.5), allergic sensitization to foods at age 1 year (OR = 2.0), any moderate to severe respiratory illness without wheezing during infancy (OR = 3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR = 3.0), rhinovirus (OR 10) and/or non-rhinovirus/RSV pathogens (OR = 3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR = 6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR = 6.6; P < .0001). Conclusion: In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus; illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.. rhinovirus| respiratory syncytial virus| virus| asthma| wheezing illnesses| allergic sensitization| atopy| infants| children| allergic disease|respiratory syncytial virus| disease severity| early-life| bronchiolitis| asthma| infection| children| risk| association| age.	SEP-2005	rhinovirus| respiratory syncytial virus| virus| asthma| wheezing illnesses| allergic sensitization| atopy| infants| children| allergic disease|respiratory syncytial virus| disease severity| early-life| bronchiolitis| asthma| infection| children| risk| association| age	Lemanske, RF; Jackson, DJ; Gangnon, RE; Evans, MD; Li, ZH; Shult, PA; Kirk, CJ; Reisdorf, E; Roberg, KA; Anderson, EL; Carlson-Dakes, KT; Adler, KJ; Gilbertson-White, S; Pappas, TE; DaSilva, DF; Tisler, CJ; Gern, JE	Rhinovirus illnesses during infancy predict subsequent childhood wheezing		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	rhinovirus; respiratory syncytial virus; virus; asthma; wheezing illnesses; allergic sensitization; atopy; infants; children; allergic disease	RESPIRATORY SYNCYTIAL VIRUS; DISEASE SEVERITY; EARLY-LIFE; BRONCHIOLITIS; ASTHMA; INFECTION; CHILDREN; RISK; ASSOCIATION; AGE	Background: The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/ or allergic diseases in early childhood is not established. Objective: To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. Methods: By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. Results: Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR] = 2.1), older siblings (OR = 2.5), allergic sensitization to foods at age 1 year (OR = 2.0), any moderate to severe respiratory illness without wheezing during infancy (OR = 3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR = 3.0), rhinovirus (OR 10) and/or non-rhinovirus/RSV pathogens (OR = 3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR = 6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR = 6.6; P < .0001). Conclusion: In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus; illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.	33	377	2005	7	10.1016/j.jaci.2005.06.024	Allergy; Immunology
Exposure to endotoxin or other bacterial components might protect against the development of atopy. Background Several recent studies have shown that growing up on a farm confers significant protection against the development of atopy. These findings point particularly towards the importance of exposure to stable dust and farm animals. It has furthermore been reported that endotoxin, an intrinsic part of the outer membrane of gram negative bacteria, is abundant in environments where livestock and poultry is kept. The aim of this study was therefore to measure the level of environmental endotoxin exposure in homes of farmers' children, children with regular contact to livestock and control children with no contact to farm animals. Methods Eighty-four farming and nonfarming families were identified in rural areas in Southern Germany and Switzerland. Samples of settled and airborne dust were collected in stables, and of settled dust indoors from kitchen floors and the children's mattresses. Endotoxin concentrations were determined by a kinetic Limulus assay. Results Endotoxin concentrations were highest in stables of farming families, but were also significantly higher indoors in dust from kitchen floors (143 EU/mg vs 39 EU/mg, P < 0.001) and children's mattresses (49479 EU/m(2) vs 9383 EU/m(2), P < 0.001) as compared to control children from nonfarming families. In addition, endotoxin levels were also significantly higher in mattresses and dust from kitchen floors in households where children had regular contact to farm animals (38.6 EU/mg and 23340 EU/m(2), respectively) as compared to control subjects. Conclusion We propose that the level of environmental exposure to endotoxin and other bacterial wall components is an important protective determinant for the development of atopic diseases in childhood.. atopy| endotoxin| children|allergic sensitization| respiratory health| airborne endotoxin| immune-responses| dust| childhood| asthma| interleukin-12| community| children.	SEP-2000	atopy| endotoxin| children|allergic sensitization| respiratory health| airborne endotoxin| immune-responses| dust| childhood| asthma| interleukin-12| community| children	von Mutius, E; Braun-Fahrlander, C; Schierl, R; Riedler, J; Ehlermann, S; Maisch, S; Waser, M; Nowak, D	Exposure to endotoxin or other bacterial components might protect against the development of atopy		CLINICAL AND EXPERIMENTAL ALLERGY	atopy; endotoxin; children	ALLERGIC SENSITIZATION; RESPIRATORY HEALTH; AIRBORNE ENDOTOXIN; IMMUNE-RESPONSES; DUST; CHILDHOOD; ASTHMA; INTERLEUKIN-12; COMMUNITY; CHILDREN	Background Several recent studies have shown that growing up on a farm confers significant protection against the development of atopy. These findings point particularly towards the importance of exposure to stable dust and farm animals. It has furthermore been reported that endotoxin, an intrinsic part of the outer membrane of gram negative bacteria, is abundant in environments where livestock and poultry is kept. The aim of this study was therefore to measure the level of environmental endotoxin exposure in homes of farmers' children, children with regular contact to livestock and control children with no contact to farm animals. Methods Eighty-four farming and nonfarming families were identified in rural areas in Southern Germany and Switzerland. Samples of settled and airborne dust were collected in stables, and of settled dust indoors from kitchen floors and the children's mattresses. Endotoxin concentrations were determined by a kinetic Limulus assay. Results Endotoxin concentrations were highest in stables of farming families, but were also significantly higher indoors in dust from kitchen floors (143 EU/mg vs 39 EU/mg, P < 0.001) and children's mattresses (49479 EU/m(2) vs 9383 EU/m(2), P < 0.001) as compared to control children from nonfarming families. In addition, endotoxin levels were also significantly higher in mattresses and dust from kitchen floors in households where children had regular contact to farm animals (38.6 EU/mg and 23340 EU/m(2), respectively) as compared to control subjects. Conclusion We propose that the level of environmental exposure to endotoxin and other bacterial wall components is an important protective determinant for the development of atopic diseases in childhood.	32	377	2000	5		Allergy; Immunology
Oxidant and antioxidant balance in the airways and airway diseases. Although oxygen is a prerequisite to life, at concentrations beyond the physiological limits it may be hazardous to the cells. Since the lungs are directly exposed to very high amounts of oxygen, it is imperative for the organ to possess defences against possible oxidative challenge. The lungs are therefore endowed with an armamentarium of a battery of endogenous agents called antioxidants. The antioxidant species help the lungs ward off the deleterious consequences of a wide variety of oxidants/reactive oxygen species such as superoxide anion, hydroxyl radical, hypohalite radical, hydrogen peroxide and reactive nitrogen species such as nitric oxide, peroxynitrite, nitrite produced endogenously and sometimes accessed through exposure to the environment. The major non-enzymatic antioxidants of the lungs are glutathione, vitamins C and E, beta-carotene, uric acid and the enzymatic antioxidants are superoxide dismutases, catalase and peroxidases. These antioxidants are the first lines of defence against the oxidants and usually act at a gross level. Recent insights into cellular redox chemistry have revealed the presence of certain specialized proteins such as peroxiredoxins, thioredoxins, glutaredoxins, heme oxygenases and reductases, which are involved in cellular adaptation and protection against an oxidative assault. These molecules usually exert their action at a more subtle level of cellular signaling processes. Aberrations in oxidant: antioxidant balance can lead to a variety of airway diseases, such as asthma, chronic obstructive Pulmonary disease and idiopathic pulmonary fibrosis which is the topic of discussion in this review. (c) 2005 Elsevier B.V. All rights reserved.. oxidants| antioxidants| lungs| glutathione| superoxide dismutase| thioredoxin|extracellular-superoxide-dismutase| idiopathic pulmonary-fibrosis| tumor-necrosis-factor| heme oxygenase-1 expression| induced lung injury| kappa-b activation| gamma-glutamylcysteine synthetase| respiratory-distress-syndrome| alveolar inflammatory cells| bronchial epithelial-cells.	MAR 8-2006	oxidants| antioxidants| lungs| glutathione| superoxide dismutase| thioredoxin|extracellular-superoxide-dismutase| idiopathic pulmonary-fibrosis| tumor-necrosis-factor| heme oxygenase-1 expression| induced lung injury| kappa-b activation| gamma-glutamylcysteine synthetase| respiratory-distress-syndrome| alveolar inflammatory cells| bronchial epithelial-cells	Rahman, I; Biswas, SK; Kode, A	Oxidant and antioxidant balance in the airways and airway diseases		EUROPEAN JOURNAL OF PHARMACOLOGY	oxidants; antioxidants; lungs; glutathione; superoxide dismutase; thioredoxin	EXTRACELLULAR-SUPEROXIDE-DISMUTASE; IDIOPATHIC PULMONARY-FIBROSIS; TUMOR-NECROSIS-FACTOR; HEME OXYGENASE-1 EXPRESSION; INDUCED LUNG INJURY; KAPPA-B ACTIVATION; GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; RESPIRATORY-DISTRESS-SYNDROME; ALVEOLAR INFLAMMATORY CELLS; BRONCHIAL EPITHELIAL-CELLS	Although oxygen is a prerequisite to life, at concentrations beyond the physiological limits it may be hazardous to the cells. Since the lungs are directly exposed to very high amounts of oxygen, it is imperative for the organ to possess defences against possible oxidative challenge. The lungs are therefore endowed with an armamentarium of a battery of endogenous agents called antioxidants. The antioxidant species help the lungs ward off the deleterious consequences of a wide variety of oxidants/reactive oxygen species such as superoxide anion, hydroxyl radical, hypohalite radical, hydrogen peroxide and reactive nitrogen species such as nitric oxide, peroxynitrite, nitrite produced endogenously and sometimes accessed through exposure to the environment. The major non-enzymatic antioxidants of the lungs are glutathione, vitamins C and E, beta-carotene, uric acid and the enzymatic antioxidants are superoxide dismutases, catalase and peroxidases. These antioxidants are the first lines of defence against the oxidants and usually act at a gross level. Recent insights into cellular redox chemistry have revealed the presence of certain specialized proteins such as peroxiredoxins, thioredoxins, glutaredoxins, heme oxygenases and reductases, which are involved in cellular adaptation and protection against an oxidative assault. These molecules usually exert their action at a more subtle level of cellular signaling processes. Aberrations in oxidant: antioxidant balance can lead to a variety of airway diseases, such as asthma, chronic obstructive Pulmonary disease and idiopathic pulmonary fibrosis which is the topic of discussion in this review. (c) 2005 Elsevier B.V. All rights reserved.	220	373	2006	18	10.1016/j.ejphar.2005.12.087	Pharmacology & Pharmacy
Suppression of allergic airway inflammation by helminth-induced regulatory T cells. Allergic diseases mediated by T helper type ( Th) 2 cell immune responses are rising dramatically in most developed countries. Exaggerated Th2 cell reactivity could result, for example, from diminished exposure to Th1 cell - inducing microbial infections. Epidemiological studies, however, indicate that Th2 cell - stimulating helminth parasites may also counteract allergies, possibly by generating regulatory T cells which suppress both Th1 and Th2 arms of immunity. We therefore tested the ability of the Th2 cell - inducing gastrointestinal nematode Heligmosomoides polygyrus to influence experimentally induced airway allergy to ovalbumin and the house dust mite allergen Der p 1. Inflammatory cell infiltrates in the lung were suppressed in infected mice compared with uninfected controls. Suppression was reversed in mice treated with antibodies to CD25. Most notably, suppression was transferable with mesenteric lymph node cells ( MLNC) from infected animals to uninfected sensitized mice, demonstrating that the effector phase was targeted. MLNC from infected animals contained elevated numbers of CD4(+)CD25(+)Foxp3(+) T cells, higher TGF-beta expression, and produced strong interleukin ( IL)-10 responses to parasite antigen. However, MLNC from IL-10-deficient animals transferred suppression to sensitized hosts, indicating that IL-10 is not the primary modulator of the allergic response. Suppression was associated with CD4(+) T cells from MLNC, with the CD4(+)CD25(+) marker defining the most active population. These data support the contention that helminth infections elicit a regulatory T cell population able to down-regulate allergen induced lung pathology in vivo.. house-dust mite| growth-factor-beta| total serum ige| immune-responses| heligmosomoides-polygyrus| hygiene hypothesis| cutting edge| childhood asthma| infection| disease.	NOV 7-2005	house-dust mite| growth-factor-beta| total serum ige| immune-responses| heligmosomoides-polygyrus| hygiene hypothesis| cutting edge| childhood asthma| infection| disease	Wilson, MS; Taylor, MD; Balic, A; Finney, CAM; Lamb, JR; Maizels, RM	Suppression of allergic airway inflammation by helminth-induced regulatory T cells		JOURNAL OF EXPERIMENTAL MEDICINE		HOUSE-DUST MITE; GROWTH-FACTOR-BETA; TOTAL SERUM IGE; IMMUNE-RESPONSES; HELIGMOSOMOIDES-POLYGYRUS; HYGIENE HYPOTHESIS; CUTTING EDGE; CHILDHOOD ASTHMA; INFECTION; DISEASE	Allergic diseases mediated by T helper type ( Th) 2 cell immune responses are rising dramatically in most developed countries. Exaggerated Th2 cell reactivity could result, for example, from diminished exposure to Th1 cell - inducing microbial infections. Epidemiological studies, however, indicate that Th2 cell - stimulating helminth parasites may also counteract allergies, possibly by generating regulatory T cells which suppress both Th1 and Th2 arms of immunity. We therefore tested the ability of the Th2 cell - inducing gastrointestinal nematode Heligmosomoides polygyrus to influence experimentally induced airway allergy to ovalbumin and the house dust mite allergen Der p 1. Inflammatory cell infiltrates in the lung were suppressed in infected mice compared with uninfected controls. Suppression was reversed in mice treated with antibodies to CD25. Most notably, suppression was transferable with mesenteric lymph node cells ( MLNC) from infected animals to uninfected sensitized mice, demonstrating that the effector phase was targeted. MLNC from infected animals contained elevated numbers of CD4(+)CD25(+)Foxp3(+) T cells, higher TGF-beta expression, and produced strong interleukin ( IL)-10 responses to parasite antigen. However, MLNC from IL-10-deficient animals transferred suppression to sensitized hosts, indicating that IL-10 is not the primary modulator of the allergic response. Suppression was associated with CD4(+) T cells from MLNC, with the CD4(+)CD25(+) marker defining the most active population. These data support the contention that helminth infections elicit a regulatory T cell population able to down-regulate allergen induced lung pathology in vivo.	73	372	2005	14	10.1084/jem.20042572	Immunology; Research & Experimental Medicine
Chemokines and chemokine receptors in leukocyte trafficking. Chemokines regulate inflammation, leukocyte trafficking, and immune cell differentiation. The role of chemokines in homing of naive T lymphocytes to secondary lymphatic organs is probably the best understood of these processes, and information on chemokines in inflammation, asthma, and neurological diseases is rapidly increasing. Over the past 15 years, understanding of the size and functional complexity of the chemokine family of peptide chemoattractants has grown substantially. In this review, we first present information regarding the structure, expression, and signaling properties of chemokines and their receptors. The second part is a systems physiology-based overview of the roles that chemokines play in tissue-specific homing of lymphocyte subsets and in trafficking of inflammatory cells. This review draws on recent experimental findings as well as current models proposed by experts in the chemokine field.. homing| chemoattractants| t cell| b cell| monocyte| neutrophil|monocyte chemoattractant protein-1| experimental autoimmune encephalomyelitis| macrophage-derived chemokine| central-nervous-system| smooth-muscle cells| c-c chemokine| experimental allergic encephalomyelitis| signal-transduction pathways| human neutrophil leukocytes| messenger-rna accumulation.	JUL-2002	homing| chemoattractants| t cell| b cell| monocyte| neutrophil|monocyte chemoattractant protein-1| experimental autoimmune encephalomyelitis| macrophage-derived chemokine| central-nervous-system| smooth-muscle cells| c-c chemokine| experimental allergic encephalomyelitis| signal-transduction pathways| human neutrophil leukocytes| messenger-rna accumulation	Olson, TS; Ley, K	Chemokines and chemokine receptors in leukocyte trafficking		AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY	homing; chemoattractants; T cell; B cell; monocyte; neutrophil	MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MACROPHAGE-DERIVED CHEMOKINE; CENTRAL-NERVOUS-SYSTEM; SMOOTH-MUSCLE CELLS; C-C CHEMOKINE; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; SIGNAL-TRANSDUCTION PATHWAYS; HUMAN NEUTROPHIL LEUKOCYTES; MESSENGER-RNA ACCUMULATION	Chemokines regulate inflammation, leukocyte trafficking, and immune cell differentiation. The role of chemokines in homing of naive T lymphocytes to secondary lymphatic organs is probably the best understood of these processes, and information on chemokines in inflammation, asthma, and neurological diseases is rapidly increasing. Over the past 15 years, understanding of the size and functional complexity of the chemokine family of peptide chemoattractants has grown substantially. In this review, we first present information regarding the structure, expression, and signaling properties of chemokines and their receptors. The second part is a systems physiology-based overview of the roles that chemokines play in tissue-specific homing of lymphocyte subsets and in trafficking of inflammatory cells. This review draws on recent experimental findings as well as current models proposed by experts in the chemokine field.	203	369	2002	22	10.1152/ajpregu.00738.2001	Physiology
"Complications of the laparoscopic Roux-en-Y gastric bypass: 1,040 patients - What have we learned?. Background: The Roux-en-Y gastric bypass (RYGBP) is one of the most common operations for morbid obesity. Laparoscopic techniques have been reported, but suffer from small numbers of patients, longer operative times and seemingly higher initial complication rates as compared to the traditional ""open"" procedure. The minimally invasive approach continues to be a challenge even to the most experienced laparoscopic surgeons. The purpose of this study is to describe our experience and complications of the laparoscopic Roux-en-Y gastric bypass with a totally hand-sewn gastrojejunostomy, Methods: 1,040 consecutive laparoscopic procedures were evaluated prospectively. Only patients who had a previous open gastric procedure were excluded initially, Eventually, even patients with failed ""open"" bariatric procedures and other gastric procedures were revised laparoscopically to the RYGBP. All patients met NIH criteria for consideration for weight reductive surgery. Results: There were no anastomotic leaks from the hand-sewn gastrojejunostomy. Early complications and open conversions were related to sub-optimal exposure and bowel fixation techniques. Several staple failures were attributed to a manufacturer redesign of an instrument, Average hospital stay was 1.9 days for all patients and 1.5 days for patients without complications, Operative times consistently approach 60 minutes. Average excess weight loss was 70% at 12 months. There were 5 deaths: perioperative pulmonary embolism (1), late pulmonary embolism (2), asthma (1), and suicide (1), Conclusions: The laparoscopic Roux-en-Y gastric bypass for morbid obesity with a totally hand-sewn gastrojejunostomy can be safely performed by the bariatric surgeon with advanced laparoscopic skills in the community setting, Fixation and closure of all potential hernia sites with non-absorbable sutures is essential. Stenosis of the hand-sewn gastrojejunal anastomosis is amenable to endoscopic balloon dilation. Meticulous attention must be paid to the operative and perioperative care of the patient.. morbid obesity| bariatric surgery| laparoscopy| gastric bypass|prospective trial| follow-up."	DEC-2000	morbid obesity| bariatric surgery| laparoscopy| gastric bypass|prospective trial| follow-up	Higa, KD; Boone, KB; Ho, TC	Complications of the laparoscopic Roux-en-Y gastric bypass: 1,040 patients - What have we learned?		OBESITY SURGERY	morbid obesity; bariatric surgery; laparoscopy; gastric bypass	PROSPECTIVE TRIAL; FOLLOW-UP	"Background: The Roux-en-Y gastric bypass (RYGBP) is one of the most common operations for morbid obesity. Laparoscopic techniques have been reported, but suffer from small numbers of patients, longer operative times and seemingly higher initial complication rates as compared to the traditional ""open"" procedure. The minimally invasive approach continues to be a challenge even to the most experienced laparoscopic surgeons. The purpose of this study is to describe our experience and complications of the laparoscopic Roux-en-Y gastric bypass with a totally hand-sewn gastrojejunostomy, Methods: 1,040 consecutive laparoscopic procedures were evaluated prospectively. Only patients who had a previous open gastric procedure were excluded initially, Eventually, even patients with failed ""open"" bariatric procedures and other gastric procedures were revised laparoscopically to the RYGBP. All patients met NIH criteria for consideration for weight reductive surgery. Results: There were no anastomotic leaks from the hand-sewn gastrojejunostomy. Early complications and open conversions were related to sub-optimal exposure and bowel fixation techniques. Several staple failures were attributed to a manufacturer redesign of an instrument, Average hospital stay was 1.9 days for all patients and 1.5 days for patients without complications, Operative times consistently approach 60 minutes. Average excess weight loss was 70% at 12 months. There were 5 deaths: perioperative pulmonary embolism (1), late pulmonary embolism (2), asthma (1), and suicide (1), Conclusions: The laparoscopic Roux-en-Y gastric bypass for morbid obesity with a totally hand-sewn gastrojejunostomy can be safely performed by the bariatric surgeon with advanced laparoscopic skills in the community setting, Fixation and closure of all potential hernia sites with non-absorbable sutures is essential. Stenosis of the hand-sewn gastrojejunal anastomosis is amenable to endoscopic balloon dilation. Meticulous attention must be paid to the operative and perioperative care of the patient."	11	366	2000	5	10.1381/096089200321593706	Surgery
Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. Context Childhood asthma is strongly associated with allergic sensitization. Studies have suggested that animal exposure during infancy reduces subsequent allergic sensitization. Objective To evaluate the relationship between dog and cat exposure in the first year of life and allergic sensitization at 6 to 7 years of age. Design, Setting, and Subjects Prospective birth cohort study of healthy, fullterm infants enrolled in a health maintenance organization in suburban Detroit, Mich, who were born between April 15,1987, and August 31,1989, and followed up yearly to a mean age of 6.7 years. Of 835 children initially in the study at birth, 474 (57%) completed follow-up evaluations at age 6 to 7 years. Main Outcome Measures Atopy, defined as any skin prick test positivity to 6 common aeroallergens (dust mites [Dermatophagoides farinae, D pteronyssinus], dog, cat, short ragweed [Ambrosia artemisiifolia], and blue grass [Poa pratensis]); seroatopy, defined as any positive allergen-specific IgE test result for the same 6 allergens or for Alternaria species. Results The prevalence of any skin prick test positivity (atopy) at age 6 to 7 years was 33.6% with no dog or cat exposure in the first year of life, 34.3% with exposure to 1 dog or cat, and 15.4% with exposure to 2 or more dogs or cats (P = .005). The prevalence of any positive allergen-specific IgE test result (seroatopy) was 38.5% with no dog or cat exposure, 41.2% with exposure to 1 dog or cat, and 17.9% with exposure to 2 or more dogs or cats (P = .003). After adjustment for cord serum IgE concentration, sex, older siblings, parental smoking, parental asthma, bedroom dust mite allergen levels at 2 years, and current dog and cat ownership, exposure to 2 or more dogs or cats in the first year of life was associated with a significantly lower risk of atopy (adjusted odds ratio, 0.23; 95% confidence interval, 0.09-0.60) and seroatopy (adjusted odds ratio, 0.33; 95% confidence interval, 0.13-0.83). Conclusion Exposure to 2 or more dogs or cats in the first year of life may reduce subsequent risk of allergic sensitization to multiple allergens during childhood.. cord-blood-ige| house-dust endotoxin| asthmatic-children| serum ige| respiratory symptoms| bronchial hyperresponsiveness| australian schoolchildren| atopic sensitization| parental history| maternal smoking.	AUG 28-2002	cord-blood-ige| house-dust endotoxin| asthmatic-children| serum ige| respiratory symptoms| bronchial hyperresponsiveness| australian schoolchildren| atopic sensitization| parental history| maternal smoking	Ownby, DR; Johnson, CC; Peterson, EL	Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		CORD-BLOOD-IGE; HOUSE-DUST ENDOTOXIN; ASTHMATIC-CHILDREN; SERUM IGE; RESPIRATORY SYMPTOMS; BRONCHIAL HYPERRESPONSIVENESS; AUSTRALIAN SCHOOLCHILDREN; ATOPIC SENSITIZATION; PARENTAL HISTORY; MATERNAL SMOKING	Context Childhood asthma is strongly associated with allergic sensitization. Studies have suggested that animal exposure during infancy reduces subsequent allergic sensitization. Objective To evaluate the relationship between dog and cat exposure in the first year of life and allergic sensitization at 6 to 7 years of age. Design, Setting, and Subjects Prospective birth cohort study of healthy, fullterm infants enrolled in a health maintenance organization in suburban Detroit, Mich, who were born between April 15,1987, and August 31,1989, and followed up yearly to a mean age of 6.7 years. Of 835 children initially in the study at birth, 474 (57%) completed follow-up evaluations at age 6 to 7 years. Main Outcome Measures Atopy, defined as any skin prick test positivity to 6 common aeroallergens (dust mites [Dermatophagoides farinae, D pteronyssinus], dog, cat, short ragweed [Ambrosia artemisiifolia], and blue grass [Poa pratensis]); seroatopy, defined as any positive allergen-specific IgE test result for the same 6 allergens or for Alternaria species. Results The prevalence of any skin prick test positivity (atopy) at age 6 to 7 years was 33.6% with no dog or cat exposure in the first year of life, 34.3% with exposure to 1 dog or cat, and 15.4% with exposure to 2 or more dogs or cats (P = .005). The prevalence of any positive allergen-specific IgE test result (seroatopy) was 38.5% with no dog or cat exposure, 41.2% with exposure to 1 dog or cat, and 17.9% with exposure to 2 or more dogs or cats (P = .003). After adjustment for cord serum IgE concentration, sex, older siblings, parental smoking, parental asthma, bedroom dust mite allergen levels at 2 years, and current dog and cat ownership, exposure to 2 or more dogs or cats in the first year of life was associated with a significantly lower risk of atopy (adjusted odds ratio, 0.23; 95% confidence interval, 0.09-0.60) and seroatopy (adjusted odds ratio, 0.33; 95% confidence interval, 0.13-0.83). Conclusion Exposure to 2 or more dogs or cats in the first year of life may reduce subsequent risk of allergic sensitization to multiple allergens during childhood.	60	363	2002	10	10.1001/jama.288.8.963	General & Internal Medicine
The association between asthma and allergic symptoms in children and phthalates in house dust: A nested case-control study. Global phthalate ester production has increased from very low levels at the end of World War II to approximately 3.5 million metric tons/year. The aim of the present study was to investigate potential associations between persistent allergic symptoms in children, which have increased markedly in developed countries over the past three decades, and the concentration of phthalates in dust collected from their homes. This investigation is a case-control study nested within a cohort of 10,852 children. From the cohort, we selected 198 cases with persistent allergic symptoms and 202 controls without allergic symptoms. A clinical and a technical team investigated each child and her or his environment. We found higher median concentrations of butyl benzyl phthalate (BBzP) in dust among cases than among controls (0.15 vs. 0.12 mg/g dust). Analyzing the case group by symptoms showed that BBzP was associated with rhinitis (p = 0.001) and eczema (p = 0.001), whereas di(2-ethylhexyl) phthalate (DEHP) was associated with asthma (p = 0.022). Furthermore, dose-response relationships for these associations are supported by trend analyses. This study, shows that phthalates, within the range of what is normally found in indoor environments, are associated with allergic symptoms in children. We believe that the different associations of symptoms for the three major phthalates-BBzP, DEHP, and di-n-butyl phthalate-can be explained by a combination of chemical physical properties and toxicologic potential. Given the phthalate exposures of children worldwide, the results from this study of Swedish children have global implications.. asthma| bbzp| children| dehp| homes| phthalates|subcutaneous injection model| expert panel report| nonindustrial indoor environments| airborne particulate matter| human reference population| di-n-butyl| developmental toxicity| human-reproduction| ntp center| di(2-ethylhexyl) phthalate.	OCT-2004	asthma| bbzp| children| dehp| homes| phthalates|subcutaneous injection model| expert panel report| nonindustrial indoor environments| airborne particulate matter| human reference population| di-n-butyl| developmental toxicity| human-reproduction| ntp center| di(2-ethylhexyl) phthalate	Bornehag, CG; Sundell, J; Weschler, CJ; Sigsgaard, T; Lundgren, B; Hasselgren, M; Hagerhed-Engman, L	The association between asthma and allergic symptoms in children and phthalates in house dust: A nested case-control study		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; BBzP; children; DEHP; homes; phthalates	SUBCUTANEOUS INJECTION MODEL; EXPERT PANEL REPORT; NONINDUSTRIAL INDOOR ENVIRONMENTS; AIRBORNE PARTICULATE MATTER; HUMAN REFERENCE POPULATION; DI-N-BUTYL; DEVELOPMENTAL TOXICITY; HUMAN-REPRODUCTION; NTP CENTER; DI(2-ETHYLHEXYL) PHTHALATE	Global phthalate ester production has increased from very low levels at the end of World War II to approximately 3.5 million metric tons/year. The aim of the present study was to investigate potential associations between persistent allergic symptoms in children, which have increased markedly in developed countries over the past three decades, and the concentration of phthalates in dust collected from their homes. This investigation is a case-control study nested within a cohort of 10,852 children. From the cohort, we selected 198 cases with persistent allergic symptoms and 202 controls without allergic symptoms. A clinical and a technical team investigated each child and her or his environment. We found higher median concentrations of butyl benzyl phthalate (BBzP) in dust among cases than among controls (0.15 vs. 0.12 mg/g dust). Analyzing the case group by symptoms showed that BBzP was associated with rhinitis (p = 0.001) and eczema (p = 0.001), whereas di(2-ethylhexyl) phthalate (DEHP) was associated with asthma (p = 0.022). Furthermore, dose-response relationships for these associations are supported by trend analyses. This study, shows that phthalates, within the range of what is normally found in indoor environments, are associated with allergic symptoms in children. We believe that the different associations of symptoms for the three major phthalates-BBzP, DEHP, and di-n-butyl phthalate-can be explained by a combination of chemical physical properties and toxicologic potential. Given the phthalate exposures of children worldwide, the results from this study of Swedish children have global implications.	40	362	2004	5	10.1289/ehp.7187	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Austrian children living on a farm have less hay fever, asthma and allergic sensitization. Background and objectives In some studies, the prevalence of hay fever and asthma has been found to be lower in children from rural areas than in children from an urban environment. We hypothesized that living on a farm might be protective against development of allergic sensitization and allergic diseases. Methods In a cross-sectional survey, parents of 2283 children aged 8-10 years from a mostly rural area in Austria answered a standardized questionnaire on allergic diseases and environmental factors. 1137 children performed a skin prick test to seven local allergens. Results The prevalence of hay fever (3.1 vs 10.3%, P = 0.0002), asthma (1.1 vs 3.9%, P = 0.017) and a positive skin prick reactivity to at least one of the common local allergens (18.8 vs 32.7%, P = 0.001) was significantly lower in children living on a farm than in children from a non-farming environment. In a multivariate logistic regression model, adjusting for genetic background, parent education, living and housing conditions and dietary factors did not change the odds ratio for the association of farming and allergic sensitization. Only after including 'regular contact with livestock and poultry' into the model did the odds ratio change significantly (cOR 0.48 95% CI 0.30-0.75 to aOR 0.75 95% CI 0.37-1.52) indicating an association between regular contact with farm animals and reduced risk of atopic sensitization. Conclusion Possible explanations for the lower prevalence of hay fever, asthma and allergic sensitization in children living on a farm might be the development of immunotolerance or the stimulation of TH1 cells and suppression of TH2 cells by increased exposure of farm children to microbial antigens in the stables or farmhouses.. allergic sensitization| asthma| farm| hay fever|environmental-factors| east-germany| prevalence| schoolchildren| atopy| stimulation| exposure| symptoms| il-12| th1.	FEB-2000	allergic sensitization| asthma| farm| hay fever|environmental-factors| east-germany| prevalence| schoolchildren| atopy| stimulation| exposure| symptoms| il-12| th1	Riedler, J; Eder, W; Oberfeld, G; Schreuer, M	Austrian children living on a farm have less hay fever, asthma and allergic sensitization		CLINICAL AND EXPERIMENTAL ALLERGY	allergic sensitization; asthma; farm; hay fever	ENVIRONMENTAL-FACTORS; EAST-GERMANY; PREVALENCE; SCHOOLCHILDREN; ATOPY; STIMULATION; EXPOSURE; SYMPTOMS; IL-12; TH1	Background and objectives In some studies, the prevalence of hay fever and asthma has been found to be lower in children from rural areas than in children from an urban environment. We hypothesized that living on a farm might be protective against development of allergic sensitization and allergic diseases. Methods In a cross-sectional survey, parents of 2283 children aged 8-10 years from a mostly rural area in Austria answered a standardized questionnaire on allergic diseases and environmental factors. 1137 children performed a skin prick test to seven local allergens. Results The prevalence of hay fever (3.1 vs 10.3%, P = 0.0002), asthma (1.1 vs 3.9%, P = 0.017) and a positive skin prick reactivity to at least one of the common local allergens (18.8 vs 32.7%, P = 0.001) was significantly lower in children living on a farm than in children from a non-farming environment. In a multivariate logistic regression model, adjusting for genetic background, parent education, living and housing conditions and dietary factors did not change the odds ratio for the association of farming and allergic sensitization. Only after including 'regular contact with livestock and poultry' into the model did the odds ratio change significantly (cOR 0.48 95% CI 0.30-0.75 to aOR 0.75 95% CI 0.37-1.52) indicating an association between regular contact with farm animals and reduced risk of atopic sensitization. Conclusion Possible explanations for the lower prevalence of hay fever, asthma and allergic sensitization in children living on a farm might be the development of immunotolerance or the stimulation of TH1 cells and suppression of TH2 cells by increased exposure of farm children to microbial antigens in the stables or farmhouses.	23	360	2000	7		Allergy; Immunology
Natural polymers for gene delivery and tissue engineering. Although the field of gene delivery is dominated by viral vectors and synthetic polymeric or lipid gene carriers, natural polymers offer distinct advantages and may help advance the field of non-viral gene therapy. Natural polymers, such as chitosan, have been successful in oral and nasal delivery due to their mucoadhesive properties. Collagen has broad utility as gene activated matrices, capable of delivering large quantities of DNA in a direct, localized manner. Most natural polymers contain reactive sites amenable for ligand conjugation, cross-linking, and other modifications that can render the polymer tailored for a range of clinical applications. Natural polymers also often possess good cytocompatibility, making them popular choices for tissue engineering scaffolding applications. The marriage of gene therapy and tissue engineering exploits the power of genetic cell engineering to provide the biochemical signals to influence proliferation or differentiation of cells. Natural polymers with their ability to serve as gene carriers and tissue engineering scaffolds are poised to play an important role in the field of regenerative medicine. This review highlights the past and present research on various applications of natural polymers as particulate and matrix delivery vehicles for gene delivery. (c) 2006 Elsevier B.V All rights reserved.. gene delivery| gene therapy| tissue engineering| natural polymers| collagen| alginate| chitosan| regenerative medicine|chitosan-dna nanoparticles| mesenchymal stem-cells| dust mite allergen| in-vivo| plasmid dna| transfection efficiency| intracellular trafficking| cationized gelatin| drug-delivery| wound repair.	JUL 7-2006	gene delivery| gene therapy| tissue engineering| natural polymers| collagen| alginate| chitosan| regenerative medicine|chitosan-dna nanoparticles| mesenchymal stem-cells| dust mite allergen| in-vivo| plasmid dna| transfection efficiency| intracellular trafficking| cationized gelatin| drug-delivery| wound repair	Dang, JM; Leong, KW	Natural polymers for gene delivery and tissue engineering		ADVANCED DRUG DELIVERY REVIEWS	gene delivery; gene therapy; tissue engineering; natural polymers; collagen; alginate; chitosan; regenerative medicine	CHITOSAN-DNA NANOPARTICLES; MESENCHYMAL STEM-CELLS; DUST MITE ALLERGEN; IN-VIVO; PLASMID DNA; TRANSFECTION EFFICIENCY; INTRACELLULAR TRAFFICKING; CATIONIZED GELATIN; DRUG-DELIVERY; WOUND REPAIR	Although the field of gene delivery is dominated by viral vectors and synthetic polymeric or lipid gene carriers, natural polymers offer distinct advantages and may help advance the field of non-viral gene therapy. Natural polymers, such as chitosan, have been successful in oral and nasal delivery due to their mucoadhesive properties. Collagen has broad utility as gene activated matrices, capable of delivering large quantities of DNA in a direct, localized manner. Most natural polymers contain reactive sites amenable for ligand conjugation, cross-linking, and other modifications that can render the polymer tailored for a range of clinical applications. Natural polymers also often possess good cytocompatibility, making them popular choices for tissue engineering scaffolding applications. The marriage of gene therapy and tissue engineering exploits the power of genetic cell engineering to provide the biochemical signals to influence proliferation or differentiation of cells. Natural polymers with their ability to serve as gene carriers and tissue engineering scaffolds are poised to play an important role in the field of regenerative medicine. This review highlights the past and present research on various applications of natural polymers as particulate and matrix delivery vehicles for gene delivery. (c) 2006 Elsevier B.V All rights reserved.	82	359	2006	13	10.1016/j.addr.2006.03.001	Pharmacology & Pharmacy
Screening for bipolar disorder in the community. Background: Our goal was to estimate the rate of positive screens for bipolar I and bipolar II disorders in the general population of the United States. Method: The Mood Disorder Questionnaire (MDQ), a validated screening instrument for bipolar I and II disorders, was sent to a sample of 127,800 people selected to represent the U.S. adult population by demographic variables. 85,358 subjects (66.8% response rate) that were 18 years of age or above returned the survey and had usable data. Of the nonrespondents, 3404 subjects matched demographically to the 2000 U.S. Census data completed a telephone interview to estimate nonresponse bias. Results: The overall positive screen rate for bipolar I and II disorders, weighted to match the 2000 U.S. Census demographics, was 3.4%. When adjusted for the nonresponse bias, the rate rose to 3.7%. Only 19.8% of the individuals with positive screens for bipolar I or II disorders reported that they had previously received a diagnosis of bipolar disorder from a physician, whereas 31.2% reported receiving a diagnosis of unipolar depression. An additional 49.0% reported receiving no diagnosis of either bipolar disorder or unipolar depression. Positive screens were more frequent in young adults and low income house-holds. The rates of migraine, allergies, asthma, and alcohol and drug abuse were substantially higher among those with positive screens. Conclusion: The positive MDQ screen rate of 3.7% suggests that nearly 4% of American adults may suffer from bipolar I and II disorders. Young adults and individuals with lower income are at greater risk for this largely underdiagnosed disorder.. psychiatric-disorders| united-states| spectrum disorder| american migraine| young-adults| prevalence| mania| epidemiology| diagnosis| suicidality.	JAN-2003	psychiatric-disorders| united-states| spectrum disorder| american migraine| young-adults| prevalence| mania| epidemiology| diagnosis| suicidality	Hirschfeld, RMA; Calabrese, JR; Weissman, MM; Reed, M; Davies, MA; Frye, MA; Keck, PE; Lewis, L; McElroy, SL; McNulty, JP; Wagner, KD	Screening for bipolar disorder in the community		JOURNAL OF CLINICAL PSYCHIATRY		PSYCHIATRIC-DISORDERS; UNITED-STATES; SPECTRUM DISORDER; AMERICAN MIGRAINE; YOUNG-ADULTS; PREVALENCE; MANIA; EPIDEMIOLOGY; DIAGNOSIS; SUICIDALITY	Background: Our goal was to estimate the rate of positive screens for bipolar I and bipolar II disorders in the general population of the United States. Method: The Mood Disorder Questionnaire (MDQ), a validated screening instrument for bipolar I and II disorders, was sent to a sample of 127,800 people selected to represent the U.S. adult population by demographic variables. 85,358 subjects (66.8% response rate) that were 18 years of age or above returned the survey and had usable data. Of the nonrespondents, 3404 subjects matched demographically to the 2000 U.S. Census data completed a telephone interview to estimate nonresponse bias. Results: The overall positive screen rate for bipolar I and II disorders, weighted to match the 2000 U.S. Census demographics, was 3.4%. When adjusted for the nonresponse bias, the rate rose to 3.7%. Only 19.8% of the individuals with positive screens for bipolar I or II disorders reported that they had previously received a diagnosis of bipolar disorder from a physician, whereas 31.2% reported receiving a diagnosis of unipolar depression. An additional 49.0% reported receiving no diagnosis of either bipolar disorder or unipolar depression. Positive screens were more frequent in young adults and low income house-holds. The rates of migraine, allergies, asthma, and alcohol and drug abuse were substantially higher among those with positive screens. Conclusion: The positive MDQ screen rate of 3.7% suggests that nearly 4% of American adults may suffer from bipolar I and II disorders. Young adults and individuals with lower income are at greater risk for this largely underdiagnosed disorder.	36	357	2003	7		Psychology; Psychiatry
The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense, inflammation, and toxicity. The proinflammatory effect of PM in the lung is characterized by increased cytokine/chemokine production and adhesion molecule expression. Moreover, there is evidence that ambient PM can act as an adjuvant for allergic sensitization, which raises the possibility that long-term PM exposure may lead to increased prevalence of asthma. In addition to ambient PM, rapid expansion of nanotechnology has introduced the potential that engineered nanoparticles (NP) may also become airborne and may contribute to pulmonary diseases by novel mechanisms that could include oxidant injury. Currently, little is known about the potential adverse health effects of these particles. In this communication, the mechanisms by which particulate pollutants, including ambient PM and engineered NP, exert their adverse effects through the generation of oxidative stress and the impacts of oxidant injury in the respiratory tract will be reviewed. The importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage will also be discussed. (c) 2008 Elsevier Inc. All rights reserved.. particulate matter| oxidative stress| asthma| dendritic cells| adjuvant effect| nanotoxicology| free radicals|diesel exhaust particles| airway epithelial-cells| rat alveolar macrophages| exhaled carbon-monoxide| long-term exposure| house-dust mite| dendritic cells| cytokine production| reactive oxygen| in-vitro.	MAY 1-2008	particulate matter| oxidative stress| asthma| dendritic cells| adjuvant effect| nanotoxicology| free radicals|diesel exhaust particles| airway epithelial-cells| rat alveolar macrophages| exhaled carbon-monoxide| long-term exposure| house-dust mite| dendritic cells| cytokine production| reactive oxygen| in-vitro	Li, N; Xia, T; Nel, AE	The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles		FREE RADICAL BIOLOGY AND MEDICINE	particulate matter; oxidative stress; asthma; dendritic cells; adjuvant effect; nanotoxicology; free radicals	DIESEL EXHAUST PARTICLES; AIRWAY EPITHELIAL-CELLS; RAT ALVEOLAR MACROPHAGES; EXHALED CARBON-MONOXIDE; LONG-TERM EXPOSURE; HOUSE-DUST MITE; DENDRITIC CELLS; CYTOKINE PRODUCTION; REACTIVE OXYGEN; IN-VITRO	Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense, inflammation, and toxicity. The proinflammatory effect of PM in the lung is characterized by increased cytokine/chemokine production and adhesion molecule expression. Moreover, there is evidence that ambient PM can act as an adjuvant for allergic sensitization, which raises the possibility that long-term PM exposure may lead to increased prevalence of asthma. In addition to ambient PM, rapid expansion of nanotechnology has introduced the potential that engineered nanoparticles (NP) may also become airborne and may contribute to pulmonary diseases by novel mechanisms that could include oxidant injury. Currently, little is known about the potential adverse health effects of these particles. In this communication, the mechanisms by which particulate pollutants, including ambient PM and engineered NP, exert their adverse effects through the generation of oxidative stress and the impacts of oxidant injury in the respiratory tract will be reviewed. The importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage will also be discussed. (c) 2008 Elsevier Inc. All rights reserved.	124	356	2008	11	10.1016/j.freeradbiomed.2008.01.028	Biochemistry & Molecular Biology; Endocrinology & Metabolism
Moving to opportunity in Boston: Early results of a randomized mobility experiment. We examine short-run impacts of changes in residential neighborhoods on the well-being of families residing in high-poverty public housing projects who received Section 8 housing vouchers through a random lottery. Households offered vouchers experienced improvements in multiple measures of well-being relative to a control group, including increased safety, improved health among household heads, and fewer behavior problems among boys. There were no significant short-run impacts of vouchers on the employment, earnings, or welfare receipt of household heads. Children in households offered vouchers valid only in low poverty neighborhoods also had reduced likelihood of injuries, asthma attacks, and victimizations by crime.. children| neighborhoods| identification| externalities| education| community| program| matter| city.	MAY-2001	children| neighborhoods| identification| externalities| education| community| program| matter| city	Katz, LF; Kling, JR; Liebman, JB	Moving to opportunity in Boston: Early results of a randomized mobility experiment		QUARTERLY JOURNAL OF ECONOMICS		CHILDREN; NEIGHBORHOODS; IDENTIFICATION; EXTERNALITIES; EDUCATION; COMMUNITY; PROGRAM; MATTER; CITY	We examine short-run impacts of changes in residential neighborhoods on the well-being of families residing in high-poverty public housing projects who received Section 8 housing vouchers through a random lottery. Households offered vouchers experienced improvements in multiple measures of well-being relative to a control group, including increased safety, improved health among household heads, and fewer behavior problems among boys. There were no significant short-run impacts of vouchers on the employment, earnings, or welfare receipt of household heads. Children in households offered vouchers valid only in low poverty neighborhoods also had reduced likelihood of injuries, asthma attacks, and victimizations by crime.	69	356	2001	48	10.1162/00335530151144113	Business & Economics
Particulate air pollutants and asthma - A paradigm for the role of oxidative stress in PM-induced adverse health effects. Asthma is a chronic inflammatory disease, which involves a variety of different mediators, including reactive oxygen species. There is growing awareness that particulate pollutants act as adjuvants during allergic sensitization and can also induce acute asthma exacerbations. In this communication we review the role of oxidative stress in asthma, with an emphasis on the pro-oxidative effects of diesel exhaust particles and their chemicals in the respiratory tract. We review the biology of oxidative stress, including protective and injurious effects that explain the impact of particulate matter-induced oxidative stress in asthma. (C) 2003 Elsevier Inc. All rights reserved.. antioxidant enzyme| asthma exacerbation| diesel exhaust particles| inflammation| particulate matter| polycyclic aromatic hydrocarbons| quinone| reactive oxygen species| redox cycling| stratified oxidative stress response|diesel exhaust particles| glutathione-s-transferase| induced eosinophilic inflammation| antioxidant response elements| bronchial epithelial-cells| expired breath condensate| murine strain differences| exhaled carbon-monoxide| nitric-oxide| superoxide-dismutase.	DEC-2003	antioxidant enzyme| asthma exacerbation| diesel exhaust particles| inflammation| particulate matter| polycyclic aromatic hydrocarbons| quinone| reactive oxygen species| redox cycling| stratified oxidative stress response|diesel exhaust particles| glutathione-s-transferase| induced eosinophilic inflammation| antioxidant response elements| bronchial epithelial-cells| expired breath condensate| murine strain differences| exhaled carbon-monoxide| nitric-oxide| superoxide-dismutase	Li, N; Hao, MQ; Phalen, RF; Hinds, WC; Nel, AE	Particulate air pollutants and asthma - A paradigm for the role of oxidative stress in PM-induced adverse health effects		CLINICAL IMMUNOLOGY	antioxidant enzyme; asthma exacerbation; diesel exhaust particles; inflammation; particulate matter; polycyclic aromatic hydrocarbons; quinone; reactive oxygen species; redox cycling; stratified oxidative stress response	DIESEL EXHAUST PARTICLES; GLUTATHIONE-S-TRANSFERASE; INDUCED EOSINOPHILIC INFLAMMATION; ANTIOXIDANT RESPONSE ELEMENTS; BRONCHIAL EPITHELIAL-CELLS; EXPIRED BREATH CONDENSATE; MURINE STRAIN DIFFERENCES; EXHALED CARBON-MONOXIDE; NITRIC-OXIDE; SUPEROXIDE-DISMUTASE	Asthma is a chronic inflammatory disease, which involves a variety of different mediators, including reactive oxygen species. There is growing awareness that particulate pollutants act as adjuvants during allergic sensitization and can also induce acute asthma exacerbations. In this communication we review the role of oxidative stress in asthma, with an emphasis on the pro-oxidative effects of diesel exhaust particles and their chemicals in the respiratory tract. We review the biology of oxidative stress, including protective and injurious effects that explain the impact of particulate matter-induced oxidative stress in asthma. (C) 2003 Elsevier Inc. All rights reserved.	151	354	2003	16	10.1016/j.clim.2003.08.006	Immunology
Prevalences of positive skin test responses to 10 common allergens in the US population: Results from the Third National Health and Nutrition Examination Survey. Background: Allergy skin tests were administered in the second and third National Health and Nutrition Examination Surveys (NHANES II and III) conducted in the United States from 1976 through 1980 and 1988 through 1994, respectively. Objectives: This study estimated positive skin test response rates in NHANES III and identified predictors of one or more positive test responses. Comparisons with NHANES II were also made. Methods: In NHANES III, 10 allergens and 2 controls were tested in all subjects aged 6 to 19 years and a random half-sample of subjects aged 20 to 59 years. A wheal-based definition of a positive test response was used. Results: In NHANES III, 54.3% of the population had positive test responses to 1 or more allergens. Prevalences were 27.5% for dust mite, 26.9% for perennial rye, 26.2% for short ragweed, 26.1% for German cockroach, 18.1% for Bermuda grass, 17.0% for cat, 15.2% for Russian thistle, 13.2% for white oak, 12.9% for Alternaria alternata, and 8.6% for peanut. Among those with positive test responses, the median number of positive responses was 3.0. Adjusted odds of a positive test response were higher for the following variables: age of 20 to 29 years, male sex, minority race, western region, old homes, and lower serum cotinine levels. For the 6 allergens common to NHANES II and III, prevalences were 2.1 to 5.5 times higher in NHANES III. Conclusions: The majority of the US population represented in NHANES III was sensitized to 1 or more allergens. Whether the higher prevalences observed in NHANES III reflect true changes in prevalence or methodological differences between the surveys cannot be determined with certainty.. allergens| allergic sensitization| allergy skin test| epidemiology| nhanes ii| nhanes iii| survey|test reactivity| aeroallergens| smoking| asthma| lead| ige.	AUG-2005	allergens| allergic sensitization| allergy skin test| epidemiology| nhanes ii| nhanes iii| survey|test reactivity| aeroallergens| smoking| asthma| lead| ige	Arbes, SJ; Gergen, PJ; Elliott, L; Zeldin, DC	Prevalences of positive skin test responses to 10 common allergens in the US population: Results from the Third National Health and Nutrition Examination Survey		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergens; allergic sensitization; allergy skin test; epidemiology; NHANES II; NHANES III; survey	TEST REACTIVITY; AEROALLERGENS; SMOKING; ASTHMA; LEAD; IGE	Background: Allergy skin tests were administered in the second and third National Health and Nutrition Examination Surveys (NHANES II and III) conducted in the United States from 1976 through 1980 and 1988 through 1994, respectively. Objectives: This study estimated positive skin test response rates in NHANES III and identified predictors of one or more positive test responses. Comparisons with NHANES II were also made. Methods: In NHANES III, 10 allergens and 2 controls were tested in all subjects aged 6 to 19 years and a random half-sample of subjects aged 20 to 59 years. A wheal-based definition of a positive test response was used. Results: In NHANES III, 54.3% of the population had positive test responses to 1 or more allergens. Prevalences were 27.5% for dust mite, 26.9% for perennial rye, 26.2% for short ragweed, 26.1% for German cockroach, 18.1% for Bermuda grass, 17.0% for cat, 15.2% for Russian thistle, 13.2% for white oak, 12.9% for Alternaria alternata, and 8.6% for peanut. Among those with positive test responses, the median number of positive responses was 3.0. Adjusted odds of a positive test response were higher for the following variables: age of 20 to 29 years, male sex, minority race, western region, old homes, and lower serum cotinine levels. For the 6 allergens common to NHANES II and III, prevalences were 2.1 to 5.5 times higher in NHANES III. Conclusions: The majority of the US population represented in NHANES III was sensitized to 1 or more allergens. Whether the higher prevalences observed in NHANES III reflect true changes in prevalence or methodological differences between the surveys cannot be determined with certainty.	22	351	2005	7	10.1016/j.jaci.2005.05.017	Allergy; Immunology
Effect of exposure to traffic on lung development from 10 to 18 years of age: a cohort study. Background Whether local exposure to major roadways adversely affects lung-function growth during the period of rapid lung development that takes place between 10 and 18 years of age is unknown. This study investigated the association between residential exposure to traffic and 8-year lung-function growth. Methods In this prospective study, 3677 children (mean age 10 years [SD 0.44]) participated from 12 southern California communities that represent a wide range in regional air quality. Children were followed up for 8 years, with yearly lung-function measurements recorded. For each child, we identified several indicators of residential exposure to traffic from large roads. Regression analysis was used to establish whether 8-year growth in lung function was associated with local traffic exposure, and whether local traffic effects were independent of regional air quality Findings Children who lived within 500 m of a freeway (motorway) had substantial deficits in 8-year growth of forced expiratory volume in 1 s (FEV(1)-81 mL, p=0.01 [95% CI -143 to -18]) and maximum midexpiratory flow rate (MMEF, -127 mL/s, p=0.03 [-243 to -11), compared with children who lived at least 1500 m from a freeway. joint models showed that both local exposure to freeways and regional air pollution had detrimental, and independent, effects on lung-function growth. Pronounced deficits in attained lung function at age 18 years were recorded for those living within 500 m of a freeway, with mean percent-predicted 97.0% for FEV(1) (p=0.013, relative to >1500 m [95% CI 94.6-99.4]) and 93.4% for MMEF (p=0.006 [95% CI 89.1-97.7]). Interpretation Local exposure to traffic on a freeway has adverse effects on children's lung development, which are independent of regional air quality, and which could result in important deficits in attained lung function in later life.. southern california communities| ambient nitrogen-dioxide| outdoor air-pollution| pulmonary-function| respiratory health| function growth| childhood asthma| major highway| preadolescent children| ultrafine particles.	FEB 17-2007	southern california communities| ambient nitrogen-dioxide| outdoor air-pollution| pulmonary-function| respiratory health| function growth| childhood asthma| major highway| preadolescent children| ultrafine particles	Gauderman, WJ; Vora, H; McConnell, R; Berhane, K; Gilliland, F; Thomas, D; Lurmann, F; Avol, E; Kunzli, N; Jerrett, M; Peters, J	Effect of exposure to traffic on lung development from 10 to 18 years of age: a cohort study		LANCET		SOUTHERN CALIFORNIA COMMUNITIES; AMBIENT NITROGEN-DIOXIDE; OUTDOOR AIR-POLLUTION; PULMONARY-FUNCTION; RESPIRATORY HEALTH; FUNCTION GROWTH; CHILDHOOD ASTHMA; MAJOR HIGHWAY; PREADOLESCENT CHILDREN; ULTRAFINE PARTICLES	Background Whether local exposure to major roadways adversely affects lung-function growth during the period of rapid lung development that takes place between 10 and 18 years of age is unknown. This study investigated the association between residential exposure to traffic and 8-year lung-function growth. Methods In this prospective study, 3677 children (mean age 10 years [SD 0.44]) participated from 12 southern California communities that represent a wide range in regional air quality. Children were followed up for 8 years, with yearly lung-function measurements recorded. For each child, we identified several indicators of residential exposure to traffic from large roads. Regression analysis was used to establish whether 8-year growth in lung function was associated with local traffic exposure, and whether local traffic effects were independent of regional air quality Findings Children who lived within 500 m of a freeway (motorway) had substantial deficits in 8-year growth of forced expiratory volume in 1 s (FEV(1)-81 mL, p=0.01 [95% CI -143 to -18]) and maximum midexpiratory flow rate (MMEF, -127 mL/s, p=0.03 [-243 to -11), compared with children who lived at least 1500 m from a freeway. joint models showed that both local exposure to freeways and regional air pollution had detrimental, and independent, effects on lung-function growth. Pronounced deficits in attained lung function at age 18 years were recorded for those living within 500 m of a freeway, with mean percent-predicted 97.0% for FEV(1) (p=0.013, relative to >1500 m [95% CI 94.6-99.4]) and 93.4% for MMEF (p=0.006 [95% CI 89.1-97.7]). Interpretation Local exposure to traffic on a freeway has adverse effects on children's lung development, which are independent of regional air quality, and which could result in important deficits in attained lung function in later life.	54	350	2007	7	10.1016/S0140-6736(07)60037-3	General & Internal Medicine
Nickel carcinogenesis. Human exposure to highly nickel-polluted environments, such as those associated with nickel refining, electroplating, and welding, has the potential to produce a variety of pathologic effects. Among them are skin allergies, lung fibrosis, and cancer of the respiratory tract. The exact mechanisms of nickel-induced carcinogenesis are not known and have been the subject of numerous epidemiologic and experimental investigations. These mechanisms are likely to involve genetic and epigenetic routes. The present review provides evidence for the genotoxic and mutagenic activity of Ni(II) particularly at high doses. Such doses are best delivered into the cells by phagocytosis of sparingly soluble nickel-containing dust particles. Ni(II) genotoxicity may be aggravated through the generation of DNA-damaging reactive oxygen species (ROS) and the inhibition of DNA repair by this metal. Broad spectrum of epigenetic effects of nickel includes alteration in gene expression resulting from DNA hypermethylation and histone hypoacetylation, as well as activation or silencing of certain genes and transcription factors, especially those involved in cellular response to hypoxia. The investigations of the pathogenic effects of nickel greatly benefit from the understanding of the chemical basis of Ni(II) interactions with intracellular targets/ligands and oxidants. Many pathogenic effects of nickel are due to the interference with the metabolism of essential metals such as Fe(II), Mn(II), Ca(II), Zn(II), or Mg(II). Research in this field allows for identification of putative Ni(II) targets relevant to carcinogenesis and prediction of pathogenic effects caused by exposure to nickel. Ultimately, the investigations of nickel carcinogenesis should be aimed at the development of treatments that would inhibit or prevent Ni(II) interactions with critical target molecules and ions, Fe(II) in particular, and thus avert the respiratory tract cancer and other adverse health effects in nickel workers. (C) 2003 Elsevier B.V. All rights reserved.. nickel carcinogenesis| epigenetic toxicity| genotoxicity| histones| hypoxia| oxidative damage.	DEC 10-2003	nickel carcinogenesis| epigenetic toxicity| genotoxicity| histones| hypoxia| oxidative damage	Kasprzak, KS; Sunderman, FW; Salnikow, K	Nickel carcinogenesis		MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS	Nickel carcinogenesis; Epigenetic toxicity; Genotoxicity; Histones; Hypoxia; Oxidative damage		Human exposure to highly nickel-polluted environments, such as those associated with nickel refining, electroplating, and welding, has the potential to produce a variety of pathologic effects. Among them are skin allergies, lung fibrosis, and cancer of the respiratory tract. The exact mechanisms of nickel-induced carcinogenesis are not known and have been the subject of numerous epidemiologic and experimental investigations. These mechanisms are likely to involve genetic and epigenetic routes. The present review provides evidence for the genotoxic and mutagenic activity of Ni(II) particularly at high doses. Such doses are best delivered into the cells by phagocytosis of sparingly soluble nickel-containing dust particles. Ni(II) genotoxicity may be aggravated through the generation of DNA-damaging reactive oxygen species (ROS) and the inhibition of DNA repair by this metal. Broad spectrum of epigenetic effects of nickel includes alteration in gene expression resulting from DNA hypermethylation and histone hypoacetylation, as well as activation or silencing of certain genes and transcription factors, especially those involved in cellular response to hypoxia. The investigations of the pathogenic effects of nickel greatly benefit from the understanding of the chemical basis of Ni(II) interactions with intracellular targets/ligands and oxidants. Many pathogenic effects of nickel are due to the interference with the metabolism of essential metals such as Fe(II), Mn(II), Ca(II), Zn(II), or Mg(II). Research in this field allows for identification of putative Ni(II) targets relevant to carcinogenesis and prediction of pathogenic effects caused by exposure to nickel. Ultimately, the investigations of nickel carcinogenesis should be aimed at the development of treatments that would inhibit or prevent Ni(II) interactions with critical target molecules and ions, Fe(II) in particular, and thus avert the respiratory tract cancer and other adverse health effects in nickel workers. (C) 2003 Elsevier B.V. All rights reserved.	313	348	2003	31	10.1016/j.mrfmmm.2003.08.021	Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
IL-31: A new link between T cells and pruritus in atopic skin inflammation. Background: IL-31 is a novel T-cell-derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor. Objective: To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases. Methods: The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis. Results: IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo, staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro, staphylococcal enterotoxin B but not viruses or T(H)1 and T(H)2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis.. activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside. Conclusion: Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development.. il-31| pruritus| atopic dermatitis| t cells| cytokines| superantigen|activation-regulated chemokine| disease-activity| serum thymus| oncostatin-m| dermatitis| expression| receptor| eotaxin-3/ccl26| interleukin-31| recruitment.	FEB-2006	il-31| pruritus| atopic dermatitis| t cells| cytokines| superantigen|activation-regulated chemokine| disease-activity| serum thymus| oncostatin-m| dermatitis| expression| receptor| eotaxin-3/ccl26| interleukin-31| recruitment	Sonkoly, E; Muller, A; Lauerma, AI; Pivarcsi, A; Soto, H; Kemeny, L; Alenius, H; Dieu-Nosjean, MC; Meller, S; Rieker, J; Steinhoff, M; Hoffmann, TK; Ruzicka, T; Zlotnik, A; Homey, B	IL-31: A new link between T cells and pruritus in atopic skin inflammation		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	IL-31; pruritus; atopic dermatitis; T cells; cytokines; superantigen	ACTIVATION-REGULATED CHEMOKINE; DISEASE-ACTIVITY; SERUM THYMUS; ONCOSTATIN-M; DERMATITIS; EXPRESSION; RECEPTOR; EOTAXIN-3/CCL26; INTERLEUKIN-31; RECRUITMENT	Background: IL-31 is a novel T-cell-derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor. Objective: To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases. Methods: The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis. Results: IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo, staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro, staphylococcal enterotoxin B but not viruses or T(H)1 and T(H)2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis.. activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside. Conclusion: Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development.	38	346	2006	7	10.1016/j.jaci.2005.10.033	Allergy; Immunology
"Pathogenesis of asthma. While asthma is considered an inflammatory disorder of the conducting airways, it is becoming increasingly apparent that the disease is heterogeneous with respect to immunopathology, clinical phenotypes, response to therapies, and natural history. Once considered purely an allergic disorder dominated by Th2-type lymphocytes, IgE, mast cells, eosinophils, macrophages, and cytokines, the disease also involves local epithelial, mesenchymal, vascular and neurologic events that are involved in directing the Th2 phenotype to the lung and through aberrant injury-repair mechanisms to remodeling of the airway wall. Structural cells provide the necessary ""soil"" upon which the ""seeds"" of the inflammatory response are able to take root and maintain a chronic phenotype and upon which are superimposed acute and subacute episodes usually driven by environmental factors such as exposure to allergens, microorganisms, pollutants or caused by inadequate antiinflammatory treatment. Greater consideration of additional immunologic and inflammatory pathways are revealing new ways of intervening in the prevention and treatment of the disease. Thus increased focus on environmental factors beyond allergic exposure (such as virus infection, air pollution, and diet) are identifying targets in structural as well as immune and inflammatory cells at which to direct new interventions.. nerve growth-factor| airway smooth-muscle| killer t-cells| bronchial epithelial-cells| chemokine receptor-3 expression| subepithelial basement-membrane| nonatopic intrinsic asthmatics| thymic stromal lymphopoietin| mesenchymal trophic unit| necrosis-factor-alpha."	JUN-2008	nerve growth-factor| airway smooth-muscle| killer t-cells| bronchial epithelial-cells| chemokine receptor-3 expression| subepithelial basement-membrane| nonatopic intrinsic asthmatics| thymic stromal lymphopoietin| mesenchymal trophic unit| necrosis-factor-alpha	Holgate, ST	Pathogenesis of asthma		CLINICAL AND EXPERIMENTAL ALLERGY		NERVE GROWTH-FACTOR; AIRWAY SMOOTH-MUSCLE; KILLER T-CELLS; BRONCHIAL EPITHELIAL-CELLS; CHEMOKINE RECEPTOR-3 EXPRESSION; SUBEPITHELIAL BASEMENT-MEMBRANE; NONATOPIC INTRINSIC ASTHMATICS; THYMIC STROMAL LYMPHOPOIETIN; MESENCHYMAL TROPHIC UNIT; NECROSIS-FACTOR-ALPHA	"While asthma is considered an inflammatory disorder of the conducting airways, it is becoming increasingly apparent that the disease is heterogeneous with respect to immunopathology, clinical phenotypes, response to therapies, and natural history. Once considered purely an allergic disorder dominated by Th2-type lymphocytes, IgE, mast cells, eosinophils, macrophages, and cytokines, the disease also involves local epithelial, mesenchymal, vascular and neurologic events that are involved in directing the Th2 phenotype to the lung and through aberrant injury-repair mechanisms to remodeling of the airway wall. Structural cells provide the necessary ""soil"" upon which the ""seeds"" of the inflammatory response are able to take root and maintain a chronic phenotype and upon which are superimposed acute and subacute episodes usually driven by environmental factors such as exposure to allergens, microorganisms, pollutants or caused by inadequate antiinflammatory treatment. Greater consideration of additional immunologic and inflammatory pathways are revealing new ways of intervening in the prevention and treatment of the disease. Thus increased focus on environmental factors beyond allergic exposure (such as virus infection, air pollution, and diet) are identifying targets in structural as well as immune and inflammatory cells at which to direct new interventions."	262	344	2008	26	10.1111/j.1365-2222.2008.02971.x	Allergy; Immunology
Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study.. Background Specific immunotherapy (SIT) is a recognized way of treating IgE-mediated respiratory diseases. The clinical outcome is usually better in allergic children than in adults. Objective To increase our knowledge of the ability of SIT to prevent the onset of new sensitizations in monosensitized subjects, so far poorly documented. Methods 134 children (age range 5-8 years), who had intermittent asthma with or without rhinitis, with single sensitization to mite allergen (skin prick test and serum-specific IgE), were enrolled. SIT was proposed to all the children's parents, but was accepted by only 75 of them (SIT Group). The remaining 63 children were treated with medication only, and were considered the Control Group. Injective SIT with mite mix was administered to the SIT Group during the first three years and all patients were followed for a total of 6 years. All patients were checked for allergic sensitization(s) by skin prick test and serum-specific IgE every year until the end of the follow-up period. Results Both groups were comparable in terms of age, sex and disease characteristics. 123 children completed the follow-up study. At the end of the study, 52 out of 69 children (75.4%) in the SIT Group showed no new sensitization, compared to 18 out of 54 children (33.3%) in the Control Group (P < 0.0002). Parietaria, Gramineae and Olea were the most common allergens responsible for the new sensitization(s). Conclusions According to our data, SIT may prevent the onset of new sensitizations in children with respiratory symptoms monosensitized to house dust mite (HDM).. asthma| children| house dust mite| new sensitizations| rhinitis| specific immunotherapy|grass-pollen immunotherapy| allergen immunotherapy| interferon-gamma| dermatophagoides-pteronyssinus| messenger-rna| t-lymphocytes| onset| cells| interleukin-4| extract.	SEP-2001	asthma| children| house dust mite| new sensitizations| rhinitis| specific immunotherapy|grass-pollen immunotherapy| allergen immunotherapy| interferon-gamma| dermatophagoides-pteronyssinus| messenger-rna| t-lymphocytes| onset| cells| interleukin-4| extract	Pajno, GB; Barberio, G; De Luca, F; Morabito, L; Parmiani, S	Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study.		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; children; house dust mite; new sensitizations; rhinitis; specific immunotherapy	GRASS-POLLEN IMMUNOTHERAPY; ALLERGEN IMMUNOTHERAPY; INTERFERON-GAMMA; DERMATOPHAGOIDES-PTERONYSSINUS; MESSENGER-RNA; T-LYMPHOCYTES; ONSET; CELLS; INTERLEUKIN-4; EXTRACT	Background Specific immunotherapy (SIT) is a recognized way of treating IgE-mediated respiratory diseases. The clinical outcome is usually better in allergic children than in adults. Objective To increase our knowledge of the ability of SIT to prevent the onset of new sensitizations in monosensitized subjects, so far poorly documented. Methods 134 children (age range 5-8 years), who had intermittent asthma with or without rhinitis, with single sensitization to mite allergen (skin prick test and serum-specific IgE), were enrolled. SIT was proposed to all the children's parents, but was accepted by only 75 of them (SIT Group). The remaining 63 children were treated with medication only, and were considered the Control Group. Injective SIT with mite mix was administered to the SIT Group during the first three years and all patients were followed for a total of 6 years. All patients were checked for allergic sensitization(s) by skin prick test and serum-specific IgE every year until the end of the follow-up period. Results Both groups were comparable in terms of age, sex and disease characteristics. 123 children completed the follow-up study. At the end of the study, 52 out of 69 children (75.4%) in the SIT Group showed no new sensitization, compared to 18 out of 54 children (33.3%) in the Control Group (P < 0.0002). Parietaria, Gramineae and Olea were the most common allergens responsible for the new sensitization(s). Conclusions According to our data, SIT may prevent the onset of new sensitizations in children with respiratory symptoms monosensitized to house dust mite (HDM).	28	344	2001	6	10.1046/j.1365-2222.2001.01161.x	Allergy; Immunology
Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Dendritic cells (DCs) are generally held responsible for initiating and maintaining allergic T helper 2 (TH2)-cell responses to inhaled allergens in asthma. Although the epithelium was initially considered to function solely as a physical barrier, it is now seen as a central player in the T H 2-cell sensitization process by influencing the function of DCs. Clinically relevant allergens, as well as known environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells and DCs. A better understanding of these interactions, ascertained from human and animal studies, might lead to better prevention and treatment of asthma.. thymic stromal lymphopoietin| allergic airway inflammation| house-dust mite| bronchial lymph-node| regulatory t-cells| inhaled antigen| th2 responses| mediate tolerance| respiratory-tract| protease allergen.	MAR-2008	thymic stromal lymphopoietin| allergic airway inflammation| house-dust mite| bronchial lymph-node| regulatory t-cells| inhaled antigen| th2 responses| mediate tolerance| respiratory-tract| protease allergen	Hammad, H; Lambrecht, BN	Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma		NATURE REVIEWS IMMUNOLOGY		THYMIC STROMAL LYMPHOPOIETIN; ALLERGIC AIRWAY INFLAMMATION; HOUSE-DUST MITE; BRONCHIAL LYMPH-NODE; REGULATORY T-CELLS; INHALED ANTIGEN; TH2 RESPONSES; MEDIATE TOLERANCE; RESPIRATORY-TRACT; PROTEASE ALLERGEN	Dendritic cells (DCs) are generally held responsible for initiating and maintaining allergic T helper 2 (TH2)-cell responses to inhaled allergens in asthma. Although the epithelium was initially considered to function solely as a physical barrier, it is now seen as a central player in the T H 2-cell sensitization process by influencing the function of DCs. Clinically relevant allergens, as well as known environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells and DCs. A better understanding of these interactions, ascertained from human and animal studies, might lead to better prevention and treatment of asthma.	131	343	2008	12	10.1038/nri2275	Immunology
"The link between fungi and severe asthma: a summary of the evidence. There is current evidence to demonstrate a close association between fungal sensitisation and asthma severity. Whether such an association is causal remains to be confirmed, but this is explored by means of a detailed literature review. There is evidence from two randomised controlled trials that, in the example of allergic bronchopulmonary aspergillosis (ABPA), treatment with systemic antifungal therapy can offer a therapeutic benefit to similar to 60% of patients. ABPA is only diagnosed if a combination of clinical and immunological criteria is achieved. It is not known whether such cases are a discrete clinical entity or part of a spectrum of the pulmonary allergic response to fungi or fungal products. This paper describes the epidemiological evidence that associates severity of asthma with fungi and discusses possible pathogenetic mechanisms. Many airborne fungi are involved including species of Alternaria, Aspergillus, Cladosporium and Penicillium, and exposure may be indoors, outdoors or both. The potential for a therapeutic role of antifungal agents for patients with severe asthma and fungal sensitisation is also explored. Not only are many patients with severe asthma desperately disabled by their disease, but, in the UK alone, asthma accounts for 1,500 deaths per yr. The healthcare costs of these patients are enormous and any treatment option merits close scrutiny. Within this report, the case for the consideration of a new term related to this association is put forward. The current authors propose the term ""severe asthma with fungal sensitisation"". However, it is recognised that enhanced and precise definition of fungal sensitisation will require improvements in diagnostic testing.. aspergillosis| asthma clinical/basic investigations| asthma epidemiology| asthma immunology| fungi|allergic bronchopulmonary aspergillosis| house-dust-mite| thunderstorm-associated asthma| skin-test reactivity| occupational asthma| environmental-factors| respiratory health| airway disease| childhood asthma| difficult asthma."	MAR-2006	aspergillosis| asthma clinical/basic investigations| asthma epidemiology| asthma immunology| fungi|allergic bronchopulmonary aspergillosis| house-dust-mite| thunderstorm-associated asthma| skin-test reactivity| occupational asthma| environmental-factors| respiratory health| airway disease| childhood asthma| difficult asthma	Denning, DW; O'Driscoll, BR; Hogaboam, CM; Bowyer, P; Niven, RM	The link between fungi and severe asthma: a summary of the evidence		EUROPEAN RESPIRATORY JOURNAL	aspergillosis; asthma clinical/basic investigations; asthma epidemiology; asthma immunology; fungi	ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; HOUSE-DUST-MITE; THUNDERSTORM-ASSOCIATED ASTHMA; SKIN-TEST REACTIVITY; OCCUPATIONAL ASTHMA; ENVIRONMENTAL-FACTORS; RESPIRATORY HEALTH; AIRWAY DISEASE; CHILDHOOD ASTHMA; DIFFICULT ASTHMA	"There is current evidence to demonstrate a close association between fungal sensitisation and asthma severity. Whether such an association is causal remains to be confirmed, but this is explored by means of a detailed literature review. There is evidence from two randomised controlled trials that, in the example of allergic bronchopulmonary aspergillosis (ABPA), treatment with systemic antifungal therapy can offer a therapeutic benefit to similar to 60% of patients. ABPA is only diagnosed if a combination of clinical and immunological criteria is achieved. It is not known whether such cases are a discrete clinical entity or part of a spectrum of the pulmonary allergic response to fungi or fungal products. This paper describes the epidemiological evidence that associates severity of asthma with fungi and discusses possible pathogenetic mechanisms. Many airborne fungi are involved including species of Alternaria, Aspergillus, Cladosporium and Penicillium, and exposure may be indoors, outdoors or both. The potential for a therapeutic role of antifungal agents for patients with severe asthma and fungal sensitisation is also explored. Not only are many patients with severe asthma desperately disabled by their disease, but, in the UK alone, asthma accounts for 1,500 deaths per yr. The healthcare costs of these patients are enormous and any treatment option merits close scrutiny. Within this report, the case for the consideration of a new term related to this association is put forward. The current authors propose the term ""severe asthma with fungal sensitisation"". However, it is recognised that enhanced and precise definition of fungal sensitisation will require improvements in diagnostic testing."	135	343	2006	12	10.1183/09031936.06.00074705	Respiratory System
"Air pollution from traffic and the development of respiratory infections and asthmatic and allergic symptoms in children. Despite the important contribution of traffic sources to urban air quality, relatively few studies have evaluated the effects of traffic-related air pollution on health, such as its influence on the development of asthma and other childhood respiratory diseases. We examined the relationship between traffic-related air pollution and the development of asthmatic/allergic symptoms and respiratory infections in a birth cohort (n similar to 4,000) study in The Netherlands. A validated model was used to assign outdoor concentrations of traffic-related air pollutants (nitrogen dioxide, particulate matter less than 2.5 mum in aerodynamic diameter, and ""soot"") at the home of each subject of the cohort. Question n a! re-derived data on wheezing, dry nighttime cough, ear, nose, and throat infections, skin rash, and physician-diagnosed asthma, bronchitis, influenza, and eczema at 2 years of age were analyzed in relation to air pollutants. Adjusted odds ratios for wheezing, physician-diagnosed asthma, ear/nose/ throat infections, and flu/serious colds indicated positive associations with air pollutants, some of which reached borderline statistical significance. No associations were observed for the other health outcomes analyzed. Sensitivity analyses generally supported these results and suggested somewhat stronger associations with traffic, for asthma that was diagnosed before I year of age. These findings are subject to confirmation at older ages, when asthma can be more readily diagnosed.. asthma| allergy| respiratory infections| air pollution| vehicle emissions|nitrogen-dioxide| childhood asthma| east-germany| preschool-children| exposure| indoor| health| prevalence| outdoor| disorders."	OCT 15-2002	asthma| allergy| respiratory infections| air pollution| vehicle emissions|nitrogen-dioxide| childhood asthma| east-germany| preschool-children| exposure| indoor| health| prevalence| outdoor| disorders	Brauer, M; Hoek, G; Van Vliet, P; Meliefste, K; Fischer, PH; Wijga, A; Koopman, LP; Neijens, HJ; Gerritsen, J; Kerkhof, M; Heinrich, J; Bellander, T; Brunekreef, B	Air pollution from traffic and the development of respiratory infections and asthmatic and allergic symptoms in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; allergy; respiratory infections; air pollution; vehicle emissions	NITROGEN-DIOXIDE; CHILDHOOD ASTHMA; EAST-GERMANY; PRESCHOOL-CHILDREN; EXPOSURE; INDOOR; HEALTH; PREVALENCE; OUTDOOR; DISORDERS	"Despite the important contribution of traffic sources to urban air quality, relatively few studies have evaluated the effects of traffic-related air pollution on health, such as its influence on the development of asthma and other childhood respiratory diseases. We examined the relationship between traffic-related air pollution and the development of asthmatic/allergic symptoms and respiratory infections in a birth cohort (n similar to 4,000) study in The Netherlands. A validated model was used to assign outdoor concentrations of traffic-related air pollutants (nitrogen dioxide, particulate matter less than 2.5 mum in aerodynamic diameter, and ""soot"") at the home of each subject of the cohort. Question n a! re-derived data on wheezing, dry nighttime cough, ear, nose, and throat infections, skin rash, and physician-diagnosed asthma, bronchitis, influenza, and eczema at 2 years of age were analyzed in relation to air pollutants. Adjusted odds ratios for wheezing, physician-diagnosed asthma, ear/nose/ throat infections, and flu/serious colds indicated positive associations with air pollutants, some of which reached borderline statistical significance. No associations were observed for the other health outcomes analyzed. Sensitivity analyses generally supported these results and suggested somewhat stronger associations with traffic, for asthma that was diagnosed before I year of age. These findings are subject to confirmation at older ages, when asthma can be more readily diagnosed."	41	343	2002	7	10.1164/rccm.200108-007OC	General & Internal Medicine; Respiratory System
The biology of IgE and the basis of allergic disease. Allergic individuals exposed to minute quantities of allergen experience an immediate response. Immediate hypersensitivity reflects the permanent sensitization of mucosal mast cells by allergen-specific IgE antibodies bound to their high-affinity receptors (FcepsilonRI). A combination of factors contributes to such long-lasting sensitization of the mast cells. They include the homing of mast cells to mucosal tissues, the local synthesis of IgE, the induction of FcepsilonRI expression on mast cells by IgE, the consequent downregulation of FcgammaR (through an insufficiency of the common gamma-chains), and the exceptionally slow dissociation of IgE from FcepsilonRI. To understand the mechanism of the immediate hypersensitivity phenomenon, we need explanations of why IgE antibodies are synthesized in preference to IgG in mucosal tissues and why the IgE is so tenaciously retained on mast cell-surface receptors. There is now compelling evidence that the microenvironment of mucosal tissues of allergic disease favors class switching to IgE; and the exceptionally high affinity of IgE for FcepsilonRI can now be interpreted in terms of the recently determined crystal structures of IgE-FcepsilonRI and IgG-FcgammaR complexes. The rate of local IgE synthesis can easily compensate for the rate of the antibody dissociation from its receptors on mucosal mast cells. Effective mechanisms ensure that allergic reactions are confined to mucosal tissues, thereby minimizing the risk of systemic anaphylaxis.. ige| ige receptors| immediate hypersensitivity| allergy| mucosal immunity|fc-epsilon-ri| class-switch recombination| human b-cells| high-affinity receptor| lymphocyte terminal differentiation| immunoglobulin class switch| germline gene transcripts| antigen-presenting cells| human mast-cells| human t-cells.	2003	ige| ige receptors| immediate hypersensitivity| allergy| mucosal immunity|fc-epsilon-ri| class-switch recombination| human b-cells| high-affinity receptor| lymphocyte terminal differentiation| immunoglobulin class switch| germline gene transcripts| antigen-presenting cells| human mast-cells| human t-cells	Gould, HJ; Sutton, BJ; Beavil, AJ; Beavil, RL; McCloskey, N; Coker, HA; Fear, D; Smurthwaite, L	The biology of IgE and the basis of allergic disease		ANNUAL REVIEW OF IMMUNOLOGY	IgE; IgE receptors; immediate hypersensitivity; allergy; mucosal immunity	FC-EPSILON-RI; CLASS-SWITCH RECOMBINATION; HUMAN B-CELLS; HIGH-AFFINITY RECEPTOR; LYMPHOCYTE TERMINAL DIFFERENTIATION; IMMUNOGLOBULIN CLASS SWITCH; GERMLINE GENE TRANSCRIPTS; ANTIGEN-PRESENTING CELLS; HUMAN MAST-CELLS; HUMAN T-CELLS	Allergic individuals exposed to minute quantities of allergen experience an immediate response. Immediate hypersensitivity reflects the permanent sensitization of mucosal mast cells by allergen-specific IgE antibodies bound to their high-affinity receptors (FcepsilonRI). A combination of factors contributes to such long-lasting sensitization of the mast cells. They include the homing of mast cells to mucosal tissues, the local synthesis of IgE, the induction of FcepsilonRI expression on mast cells by IgE, the consequent downregulation of FcgammaR (through an insufficiency of the common gamma-chains), and the exceptionally slow dissociation of IgE from FcepsilonRI. To understand the mechanism of the immediate hypersensitivity phenomenon, we need explanations of why IgE antibodies are synthesized in preference to IgG in mucosal tissues and why the IgE is so tenaciously retained on mast cell-surface receptors. There is now compelling evidence that the microenvironment of mucosal tissues of allergic disease favors class switching to IgE; and the exceptionally high affinity of IgE for FcepsilonRI can now be interpreted in terms of the recently determined crystal structures of IgE-FcepsilonRI and IgG-FcgammaR complexes. The rate of local IgE synthesis can easily compensate for the rate of the antibody dissociation from its receptors on mucosal mast cells. Effective mechanisms ensure that allergic reactions are confined to mucosal tissues, thereby minimizing the risk of systemic anaphylaxis.	282	340	2003	54	10.1146/annurev.immunol.21.120601.141103	Immunology
Device selection and outcomes of aerosol therapy: Evidence-based guidelines. Background: The proliferation of inhaler devices has resulted in a confusing number of choices for clinicians who are selecting a delivery device for aerosol therapy. There are advantages and disadvantages associated with each device category. Evidence-based guidelines for the selection of the appropriate aerosol delivery device in specific clinical settings are needed. Aim: (1) To compare the efficacy and adverse effects of treatment using nebulizers vs pressurized metered-dose inhalers (MDIs) with or without a spacer/bolding chamber vs dry powder inhalers (DPIs) as delivery, systems for beta-agonists, anticholinergic agents, and corticosteroids for several commonly encountered clinical settings and patient populations, and (2) to provide recommendations to clinicians to aid them in selecting a particular aerosol delivery device for their patients. Methods: A systematic review of pertinent randomized, controlled clinical trials (RCTs) was undertaken using MEDLINE, EmBase, and the Cochrane Library databases. A broad search strategy was chosen, combining terms related to aerosol devices or drugs with the diseases of interest in various patient groups and clinical settings. Only RCTs in which the same drug was administered with different devices were included. RCTs (394 trials) assessing inhaled corticosteroid, beta(2)-agonist, and anticholinergic agents delivered by an MDI, an MDI with a spacer/holding chamber, a nebulizer, or a DPI were identified for the years 1982 to 2001. A total of 254 outcomes were tabulated. Of the 131 studies that met the eligibility criteria, only 59 (primarily those that tested beta(2)-agonists) proved to have useable data. Results: None of the pooled metaanalyses showed a significant difference between devices in any efficacy, outcome in any, patient group for each of the clinical settings that was investigated. The adverse effects that were reported were minimal and were related to the increased drug dose that was delivered. Each of the delivery devices provided similar outcomes in patients using the correct technique for inhalation. Conclusions: Devices used for the delivery of bronchodilators and steroids can be equally efficacious. When selecting an aerosol delivery device for patients with asthma and COPD, the following should be considered: device/drug availability; clinical setting; patient age and the ability to use the selected device correctly; device use with multiple medications; cost and reimbursement; drug administration time; convenience in both outpatient and inpatient settings; and physician and patient preference.. aerosols| bronchodilators| corticosteroids| drug delivery systems| dry powder inhalers| metaanalysis| metered-dose inhalers| nebulizers|metered-dose inhaler| mechanically ventilated patients| air-flow obstruction| exercise-induced asthma| dry-powder inhaler| intermittent nebulized albuterol| bronchodilator delivery methods| chlorofluorocarbon cfc inhaler| pressurized aerosol| copd patients.	JAN-2005	aerosols| bronchodilators| corticosteroids| drug delivery systems| dry powder inhalers| metaanalysis| metered-dose inhalers| nebulizers|metered-dose inhaler| mechanically ventilated patients| air-flow obstruction| exercise-induced asthma| dry-powder inhaler| intermittent nebulized albuterol| bronchodilator delivery methods| chlorofluorocarbon cfc inhaler| pressurized aerosol| copd patients	Dolovich, MB; Ahrens, RC; Hess, DR; Anderson, P; Dhand, R; Rau, JL; Smaldone, GC; Guyatt, G	Device selection and outcomes of aerosol therapy: Evidence-based guidelines		CHEST	aerosols; bronchodilators; corticosteroids; drug delivery systems; dry powder inhalers; metaanalysis; metered-dose inhalers; nebulizers	METERED-DOSE INHALER; MECHANICALLY VENTILATED PATIENTS; AIR-FLOW OBSTRUCTION; EXERCISE-INDUCED ASTHMA; DRY-POWDER INHALER; INTERMITTENT NEBULIZED ALBUTEROL; BRONCHODILATOR DELIVERY METHODS; CHLOROFLUOROCARBON CFC INHALER; PRESSURIZED AEROSOL; COPD PATIENTS	Background: The proliferation of inhaler devices has resulted in a confusing number of choices for clinicians who are selecting a delivery device for aerosol therapy. There are advantages and disadvantages associated with each device category. Evidence-based guidelines for the selection of the appropriate aerosol delivery device in specific clinical settings are needed. Aim: (1) To compare the efficacy and adverse effects of treatment using nebulizers vs pressurized metered-dose inhalers (MDIs) with or without a spacer/bolding chamber vs dry powder inhalers (DPIs) as delivery, systems for beta-agonists, anticholinergic agents, and corticosteroids for several commonly encountered clinical settings and patient populations, and (2) to provide recommendations to clinicians to aid them in selecting a particular aerosol delivery device for their patients. Methods: A systematic review of pertinent randomized, controlled clinical trials (RCTs) was undertaken using MEDLINE, EmBase, and the Cochrane Library databases. A broad search strategy was chosen, combining terms related to aerosol devices or drugs with the diseases of interest in various patient groups and clinical settings. Only RCTs in which the same drug was administered with different devices were included. RCTs (394 trials) assessing inhaled corticosteroid, beta(2)-agonist, and anticholinergic agents delivered by an MDI, an MDI with a spacer/holding chamber, a nebulizer, or a DPI were identified for the years 1982 to 2001. A total of 254 outcomes were tabulated. Of the 131 studies that met the eligibility criteria, only 59 (primarily those that tested beta(2)-agonists) proved to have useable data. Results: None of the pooled metaanalyses showed a significant difference between devices in any efficacy, outcome in any, patient group for each of the clinical settings that was investigated. The adverse effects that were reported were minimal and were related to the increased drug dose that was delivered. Each of the delivery devices provided similar outcomes in patients using the correct technique for inhalation. Conclusions: Devices used for the delivery of bronchodilators and steroids can be equally efficacious. When selecting an aerosol delivery device for patients with asthma and COPD, the following should be considered: device/drug availability; clinical setting; patient age and the ability to use the selected device correctly; device use with multiple medications; cost and reimbursement; drug administration time; convenience in both outpatient and inpatient settings; and physician and patient preference.	140	339	2005	41	10.1378/chest.127.1.335	General & Internal Medicine; Respiratory System
Toll-like receptor 2 as a major gene for asthma in children of European farmers. Background: The finding that the prevalence of asthma and allergies is less frequent in children raised on animal farms has led to the conjecture that exposure to microbial products modifies immune responses. The toll-like receptors (TLRs) represent an evolutionarily conserved family of innate immunity receptors with microbial molecules as ligands. Objectives: We reasoned that polymorphisms in genes encoding TLRs might modulate the protective effects observed in farming populations. Methods: Farmers' and nonfarmers' children living in rural areas in Austria and Germany and who were enrolled in the cross-sectional ALEX study were genotyped for single nucleotide polymorphisms in the TLR2 and TLR4 genes. The frequencies of asthma, allergic rhinitis, and atopic sensitization were compared between the genotypes in relation to exposure to farming and endotoxin. Results: Among farmers' children, those carrying a T allele in TLR2/-16934 compared with children with genotype AA were significantly less likely to have a diagnosis of asthma (3% vs 13%, P = .012), current asthma symptoms (3% vs 16%, P = .004), atopic sensitization (14% vs 27%, P = .023), and current hay fever symptoms (3% vs 14%, P = .01). The association between TLR2/-16934 and asthma among children of farmers was independent of atopy. No such association was found among children from the same rural communities but not living on farms. Conclusion: Our results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.. farming| endotoxin| asthma| atopy| children| tlr2| tlr4| gene-environment interaction|hay-fever| allergic sensitization| cell activation| innate immunity| cutting edge| exposure| lipopolysaccharide| endotoxin| recognition| atopy.	MAR-2004	farming| endotoxin| asthma| atopy| children| tlr2| tlr4| gene-environment interaction|hay-fever| allergic sensitization| cell activation| innate immunity| cutting edge| exposure| lipopolysaccharide| endotoxin| recognition| atopy	Eder, W; Klimecki, W; Yu, LZ; von Mutius, E; Riedler, J; Braun-Fahrlander, C; Nowak, D; Martinez, FD	Toll-like receptor 2 as a major gene for asthma in children of European farmers		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	farming; endotoxin; asthma; atopy; children; TLR2; TLR4; gene-environment interaction	HAY-FEVER; ALLERGIC SENSITIZATION; CELL ACTIVATION; INNATE IMMUNITY; CUTTING EDGE; EXPOSURE; LIPOPOLYSACCHARIDE; ENDOTOXIN; RECOGNITION; ATOPY	Background: The finding that the prevalence of asthma and allergies is less frequent in children raised on animal farms has led to the conjecture that exposure to microbial products modifies immune responses. The toll-like receptors (TLRs) represent an evolutionarily conserved family of innate immunity receptors with microbial molecules as ligands. Objectives: We reasoned that polymorphisms in genes encoding TLRs might modulate the protective effects observed in farming populations. Methods: Farmers' and nonfarmers' children living in rural areas in Austria and Germany and who were enrolled in the cross-sectional ALEX study were genotyped for single nucleotide polymorphisms in the TLR2 and TLR4 genes. The frequencies of asthma, allergic rhinitis, and atopic sensitization were compared between the genotypes in relation to exposure to farming and endotoxin. Results: Among farmers' children, those carrying a T allele in TLR2/-16934 compared with children with genotype AA were significantly less likely to have a diagnosis of asthma (3% vs 13%, P = .012), current asthma symptoms (3% vs 16%, P = .004), atopic sensitization (14% vs 27%, P = .023), and current hay fever symptoms (3% vs 14%, P = .01). The association between TLR2/-16934 and asthma among children of farmers was independent of atopy. No such association was found among children from the same rural communities but not living on farms. Conclusion: Our results suggest that genetic variation in TLR2 is a major determinant of the susceptibility to asthma and allergies in children of farmers.	31	338	2004	7	10.1016/j.jaci.2003.12.374	Allergy; Immunology
An etiological role for aeroallergens and eosinophils in experimental esophagitis. Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.. gastroesophageal reflux| chemokine eotaxin| antigen| asthma| airways| mouse| interleukin-5| inflammation| allergen| children.	JAN-2001	gastroesophageal reflux| chemokine eotaxin| antigen| asthma| airways| mouse| interleukin-5| inflammation| allergen| children	Mishra, A; Hogan, SP; Brandt, EB; Rothenberg, ME	An etiological role for aeroallergens and eosinophils in experimental esophagitis		JOURNAL OF CLINICAL INVESTIGATION		GASTROESOPHAGEAL REFLUX; CHEMOKINE EOTAXIN; ANTIGEN; ASTHMA; AIRWAYS; MOUSE; INTERLEUKIN-5; INFLAMMATION; ALLERGEN; CHILDREN	Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.	37	337	2001	8	10.1172/JCI10224	Research & Experimental Medicine
Cleaning products and air fresheners: exposure to primary and secondary air pollutants. Building occupants, including cleaning personnel, are exposed to a wide variety of airborne chemicals when cleaning agents and air fresheners are used in buildings. Certain of these chemicals are listed by the state of California as toxic air contaminants (TACs) and a subset of these are regulated by the US federal government as hazardous air pollutants (HAPs). California's Proposition 65 list of species recognized as carcinogens or reproductive toxicants also includes constituents of certain cleaning products and air fresheners. In addition, many cleaning agents and air fresheners contain chemicals that can react with other air contaminants to yield potentially harmful secondary products. For example, terpenes can react rapidly with ozone in indoor air generating many secondary pollutants, including TACs such as formaldehyde. Furthermore, ozone-terpene reactions produce the hydroxyl radical, which reacts rapidly with organics, leading to the formation of other potentially toxic air pollutants. Indoor reactive chemistry involving the nitrate radical and cleaning-product constituents is also of concern, since it produces organic nitrates as well as some of the same oxidation products generated by ozone and hydroxyl radicals. Few studies have directly addressed the indoor concentrations of TACs that might result from primary emissions or secondary pollutant formation following the use of cleaning agents and air fresheners. In this paper, we combine direct empirical evidence with the basic principles of indoor pollutant behavior and with information from relevant studies, to analyze and critically assess air pollutant exposures resulting from the use of cleaning products and air fresheners. Attention is focused on compounds that are listed as HAPs, TACs or Proposition 65 carcinogens/reproductive toxicants and compounds that can readily react to generate secondary pollutants. The toxicity of many of these secondary pollutants has yet to be evaluated. The inhalation intake of airborne organic compounds from cleaning product use is estimated to be of the order of 10 mg d(-1) person(-1) in California. More than two dozen research articles present evidence of adverse health effects from inhalation exposure associated with cleaning or cleaning products. Exposure to primary and secondary pollutants depends on the complex interplay of many sets of factors and processes, including cleaning product composition, usage, building occupancy, emission dynamics, transport and mixing, building ventilation, sorptive interactions with building surfaces, and reactive chemistry. Current understanding is sufficient to describe the influence of these variables qualitatively in most cases and quantitatively in a few. (C) 2004 Elsevier Ltd. All rights reserved.. indoor air quality| hazardous air pollutants| terpenes| ozone| hydroxyl radical| nitrate radical|volatile organic-compounds| gas-phase reactions| mixing household cleaners| oh radical formation| oxidized d-limonene| indoor air| no3 radicals| rate constants| occupational asthma| building-materials.	JUN-2004	indoor air quality| hazardous air pollutants| terpenes| ozone| hydroxyl radical| nitrate radical|volatile organic-compounds| gas-phase reactions| mixing household cleaners| oh radical formation| oxidized d-limonene| indoor air| no3 radicals| rate constants| occupational asthma| building-materials	Nazaroff, WW; Weschler, CJ	Cleaning products and air fresheners: exposure to primary and secondary air pollutants		ATMOSPHERIC ENVIRONMENT	indoor air quality; hazardous air pollutants; terpenes; ozone; hydroxyl radical; nitrate radical	VOLATILE ORGANIC-COMPOUNDS; GAS-PHASE REACTIONS; MIXING HOUSEHOLD CLEANERS; OH RADICAL FORMATION; OXIDIZED D-LIMONENE; INDOOR AIR; NO3 RADICALS; RATE CONSTANTS; OCCUPATIONAL ASTHMA; BUILDING-MATERIALS	Building occupants, including cleaning personnel, are exposed to a wide variety of airborne chemicals when cleaning agents and air fresheners are used in buildings. Certain of these chemicals are listed by the state of California as toxic air contaminants (TACs) and a subset of these are regulated by the US federal government as hazardous air pollutants (HAPs). California's Proposition 65 list of species recognized as carcinogens or reproductive toxicants also includes constituents of certain cleaning products and air fresheners. In addition, many cleaning agents and air fresheners contain chemicals that can react with other air contaminants to yield potentially harmful secondary products. For example, terpenes can react rapidly with ozone in indoor air generating many secondary pollutants, including TACs such as formaldehyde. Furthermore, ozone-terpene reactions produce the hydroxyl radical, which reacts rapidly with organics, leading to the formation of other potentially toxic air pollutants. Indoor reactive chemistry involving the nitrate radical and cleaning-product constituents is also of concern, since it produces organic nitrates as well as some of the same oxidation products generated by ozone and hydroxyl radicals. Few studies have directly addressed the indoor concentrations of TACs that might result from primary emissions or secondary pollutant formation following the use of cleaning agents and air fresheners. In this paper, we combine direct empirical evidence with the basic principles of indoor pollutant behavior and with information from relevant studies, to analyze and critically assess air pollutant exposures resulting from the use of cleaning products and air fresheners. Attention is focused on compounds that are listed as HAPs, TACs or Proposition 65 carcinogens/reproductive toxicants and compounds that can readily react to generate secondary pollutants. The toxicity of many of these secondary pollutants has yet to be evaluated. The inhalation intake of airborne organic compounds from cleaning product use is estimated to be of the order of 10 mg d(-1) person(-1) in California. More than two dozen research articles present evidence of adverse health effects from inhalation exposure associated with cleaning or cleaning products. Exposure to primary and secondary pollutants depends on the complex interplay of many sets of factors and processes, including cleaning product composition, usage, building occupancy, emission dynamics, transport and mixing, building ventilation, sorptive interactions with building surfaces, and reactive chemistry. Current understanding is sufficient to describe the influence of these variables qualitatively in most cases and quantitatively in a few. (C) 2004 Elsevier Ltd. All rights reserved.	183	336	2004	25	10.1016/j.atmosenv.2004.02.040	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Risk factors of readmission to hospital for a COPD exacerbation: a prospective study. Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are a leading cause of admission to hospital among men in many countries, although the factors causing exacerbations are largely unknown. The association between readmission for a COPD exacerbation and a wide range of modifiable potential risk factors, after adjusting for sociodemographic and clinical factors, has been assessed. Methods: Three hundred and forty patients with COPD recruited during an admission for an exacerbation in four tertiary hospitals in the Barcelona area of Spain were followed for a mean period of 1.1 years. Information on potential risk factors, including clinical and functional status, medical care and prescriptions, medication adherence, lifestyle, health status, and social support, was collected at the recruitment admission. A Cox's proportional hazards model was used to obtain independent relative risks of readmission for COPD. Results: During the follow up period 63% of patients were readmitted at least once, and 29% died. The final multivariate model showed the following risk (or protective) factors: greater than or equal to3 admissions for COPD in the year before recruitment (hazard ratio (HR)= 1.66, 95% Cl 1.16 to 2.39), forced expiratory volume in 1 second (FEV1 percentage predicted (0.97, 95% Cl 0.96 to 0.99), oxygen tension (0.88, 95% Cl 0.79 to 0.98), higher levels of usual physical activity (0.54, 95% Cl 0.34 to 0.86), and taking anticholinergic drugs (1.81, 95% 1.11 to 2.94). Exposure to passive smoking was also related to an increased risk of readmission with COPD after adjustment for clinical factors (1.63, 95% Cl 1.04 to 2.57) but did not remain in the final model. Conclusions: This is the first study to show a strong association between usual physical activity and reduced risk of readmission to hospital with COPD, which is potentially relevant for rehabilitation and other therapeutic strategies.. obstructive pulmonary-disease| chronic lung-disease| quality-of-life| physical activities| asthma| mortality| questionnaire| efram.	FEB-2003	obstructive pulmonary-disease| chronic lung-disease| quality-of-life| physical activities| asthma| mortality| questionnaire| efram	Garcia-Aymerich, J; Farrero, E; Felez, MA; Izquierdo, J; Marrades, RM; Anto, JM	Risk factors of readmission to hospital for a COPD exacerbation: a prospective study		THORAX		OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC LUNG-DISEASE; QUALITY-OF-LIFE; PHYSICAL ACTIVITIES; ASTHMA; MORTALITY; QUESTIONNAIRE; EFRAM	Background: Exacerbations of chronic obstructive pulmonary disease (COPD) are a leading cause of admission to hospital among men in many countries, although the factors causing exacerbations are largely unknown. The association between readmission for a COPD exacerbation and a wide range of modifiable potential risk factors, after adjusting for sociodemographic and clinical factors, has been assessed. Methods: Three hundred and forty patients with COPD recruited during an admission for an exacerbation in four tertiary hospitals in the Barcelona area of Spain were followed for a mean period of 1.1 years. Information on potential risk factors, including clinical and functional status, medical care and prescriptions, medication adherence, lifestyle, health status, and social support, was collected at the recruitment admission. A Cox's proportional hazards model was used to obtain independent relative risks of readmission for COPD. Results: During the follow up period 63% of patients were readmitted at least once, and 29% died. The final multivariate model showed the following risk (or protective) factors: greater than or equal to3 admissions for COPD in the year before recruitment (hazard ratio (HR)= 1.66, 95% Cl 1.16 to 2.39), forced expiratory volume in 1 second (FEV1 percentage predicted (0.97, 95% Cl 0.96 to 0.99), oxygen tension (0.88, 95% Cl 0.79 to 0.98), higher levels of usual physical activity (0.54, 95% Cl 0.34 to 0.86), and taking anticholinergic drugs (1.81, 95% 1.11 to 2.94). Exposure to passive smoking was also related to an increased risk of readmission with COPD after adjustment for clinical factors (1.63, 95% Cl 1.04 to 2.57) but did not remain in the final model. Conclusions: This is the first study to show a strong association between usual physical activity and reduced risk of readmission to hospital with COPD, which is potentially relevant for rehabilitation and other therapeutic strategies.	36	336	2003	6	10.1136/thorax.58.2.100	Respiratory System
Advancing the science of symptom management. Since the publication of the original Symptom Management Model (Larson et al. 1994), faculty and students at the University of California, San Francisco (UCSF) School of Nursing Centre for System Management have tested this model in research studies and expanded the model through collegial discussions and seminars. Aim. In this paper, we describe the evidence-based revised conceptual model, the three dimensions of the model, and the areas where further research is needed. Background/Rationale. The experience of symptoms, minor to severe, prompts millions of patients to visit their healthcare providers each year. Symptoms not only create distress, but also disrupt social functioning. The management of symptoms and their resulting outcomes often become the responsibility of the patient and his or her family members. Healthcare providers have difficulty developing symptom management strategies that can be applied across acute and home-care settings because few models of symptom management have been tested empirically. To date, the majority of research on symptoms was directed toward studying a single symptom, such as pain or fatigue, or toward evaluating associated symptoms, such as depression and sleep disturbance. While this approach has advanced our understanding of some symptoms, we offer a generic symptom management model to provide direction for selecting clinical interventions, informing research, and bridging an array of symptoms associated with a variety of diseases and conditions. Finally, a broadly-based symptom management model allows the integration of science from other fields.. concepts/constructs related to health| symptom management model| symptom management theory|type-2 diabetes management| american midlife women| practitioner perspectives| contrasting patient| pain| experience| asthma| stimulation| education| patterns.	MAR-2001	concepts/constructs related to health| symptom management model| symptom management theory|type-2 diabetes management| american midlife women| practitioner perspectives| contrasting patient| pain| experience| asthma| stimulation| education| patterns	Dodd, M; Janson, S; Facione, N; Faucett, J; Froelicher, ES; Humphreys, J; Lee, K; Miaskowski, C; Puntillo, K; Rankin, S; Taylor, D	Advancing the science of symptom management		JOURNAL OF ADVANCED NURSING	concepts/constructs related to health; symptom management model; symptom management theory	TYPE-2 DIABETES MANAGEMENT; AMERICAN MIDLIFE WOMEN; PRACTITIONER PERSPECTIVES; CONTRASTING PATIENT; PAIN; EXPERIENCE; ASTHMA; STIMULATION; EDUCATION; PATTERNS	Since the publication of the original Symptom Management Model (Larson et al. 1994), faculty and students at the University of California, San Francisco (UCSF) School of Nursing Centre for System Management have tested this model in research studies and expanded the model through collegial discussions and seminars. Aim. In this paper, we describe the evidence-based revised conceptual model, the three dimensions of the model, and the areas where further research is needed. Background/Rationale. The experience of symptoms, minor to severe, prompts millions of patients to visit their healthcare providers each year. Symptoms not only create distress, but also disrupt social functioning. The management of symptoms and their resulting outcomes often become the responsibility of the patient and his or her family members. Healthcare providers have difficulty developing symptom management strategies that can be applied across acute and home-care settings because few models of symptom management have been tested empirically. To date, the majority of research on symptoms was directed toward studying a single symptom, such as pain or fatigue, or toward evaluating associated symptoms, such as depression and sleep disturbance. While this approach has advanced our understanding of some symptoms, we offer a generic symptom management model to provide direction for selecting clinical interventions, informing research, and bridging an array of symptoms associated with a variety of diseases and conditions. Finally, a broadly-based symptom management model allows the integration of science from other fields.	49	336	2001	9	10.1046/j.1365-2648.2001.01697.x	Nursing
Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study. Background Breastfeeding is widely advocated to reduce risk of atopy and asthma, but the evidence for such an effect is conflicting. We aimed to assess long-term outcomes of asthma and atopy related to breastfeeding in a New Zealand birth cohort. Methods Our cohort consisted of 1037 of 1139 children born in Dunedin, New Zealand, between April, 1972, and March, 1973, and residing in Otago province at age 3 years. Children were assessed every 2-5 years from ages 9 to 26 years with respiratory questionnaires, pulmonary function, bronchial challenge, and allergy skin tests. History of breastfeeding had been independently recorded in early childhood. Findings 504 (49%) of 1037 eligible children were breastfed (4 weeks or longer) and 533 (51%) were not. More children who were breastfed were atopic at all ages from 13 to 21 years to cats (p=0.0001), house dust mites (p=0.0010), and grass pollen (p<0.0001) than those who were not. More children who were breastfed reported current asthma at each assessment between age 9 (p=0.0008) and 26 years (p=0.0008) than those who were not. Breastfeeding effects were not affected by parental history of hayfever or asthma. Multifactor analysis controlling for socioeconomic status, parental smoking, birth order, and use of sheepskin bedding in infancy, showed odds ratios of 1.94 (95% Cl 1.42-2-65, p<0.0001) for any allergen positive at age 13 years, 2.40 (1-36-4.26, p=0.0003) for current asthma at 9 years, and 1.83 (1.35-2.47, p<0.0001) for current asthma at 9-26 years by repeated-measures analysis. Interpretation Breastfeeding does not protect children against atopy and asthma and may even increase the risk.. childhood asthma| new-zealand| fed infants| epidemiology| microflora| allergy| birth.	SEP 21-2002	childhood asthma| new-zealand| fed infants| epidemiology| microflora| allergy| birth	Sears, MR; Greene, JM; Willan, AR; Taylor, DR; Flannery, EM; Cowan, JO; Herbison, GP; Poulton, R	Long-term relation between breastfeeding and development of atopy and asthma in children and young adults: a longitudinal study		LANCET		CHILDHOOD ASTHMA; NEW-ZEALAND; FED INFANTS; EPIDEMIOLOGY; MICROFLORA; ALLERGY; BIRTH	Background Breastfeeding is widely advocated to reduce risk of atopy and asthma, but the evidence for such an effect is conflicting. We aimed to assess long-term outcomes of asthma and atopy related to breastfeeding in a New Zealand birth cohort. Methods Our cohort consisted of 1037 of 1139 children born in Dunedin, New Zealand, between April, 1972, and March, 1973, and residing in Otago province at age 3 years. Children were assessed every 2-5 years from ages 9 to 26 years with respiratory questionnaires, pulmonary function, bronchial challenge, and allergy skin tests. History of breastfeeding had been independently recorded in early childhood. Findings 504 (49%) of 1037 eligible children were breastfed (4 weeks or longer) and 533 (51%) were not. More children who were breastfed were atopic at all ages from 13 to 21 years to cats (p=0.0001), house dust mites (p=0.0010), and grass pollen (p<0.0001) than those who were not. More children who were breastfed reported current asthma at each assessment between age 9 (p=0.0008) and 26 years (p=0.0008) than those who were not. Breastfeeding effects were not affected by parental history of hayfever or asthma. Multifactor analysis controlling for socioeconomic status, parental smoking, birth order, and use of sheepskin bedding in infancy, showed odds ratios of 1.94 (95% Cl 1.42-2-65, p<0.0001) for any allergen positive at age 13 years, 2.40 (1-36-4.26, p=0.0003) for current asthma at 9 years, and 1.83 (1.35-2.47, p<0.0001) for current asthma at 9-26 years by repeated-measures analysis. Interpretation Breastfeeding does not protect children against atopy and asthma and may even increase the risk.	37	335	2002	7	10.1016/S0140-6736(02)11025-7	General & Internal Medicine
"Allergic rhinitis: Definition, epidemiology, detection, and pathophysiology, diagnosis. Allergic rhinitis (AR) is a heterogeneous disorder that despite its high prevalence is often undiagnosed. It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea. Many causative agents have been linked to AR including pollens, molds, dust mites, and animal dander. Seasonal allergic rhinitis (SAR) is fairly easy to identify because of the rapid and reproducible onset and offset of symptoms in association with pollen exposure. Perennial AR is often more difficult to detect than SAR because of the overlap with sinusitis, respiratory infections, and vasomotor rhinitis. SAR can result in hyperresponsiveness to allergens such as cigarette smoke, once pollen season is over. Perennial AR is defined as occurring during approximately 9 months of the year. AR affects an estimated 20 to 40 million people in the United States alone, and the incidence is increasing; an estimated 20% of cases are SAR; 40% of cases are perennial rhinitis; and 40% of cases are mixed. The pathophysiology of SAR is complex. There is a strong genetic component to the allergic response, which is driven through mucosal infiltration and action on plasma cells, roast cells, and eosinophils. The allergic response occurs in two phases, which are considered the ""early"" and ""late"" phase responses. Early phase response occurs within minutes of exposure to the allergen and tends to produce sneezing, itching, and clear rhinorrhea; late phase response occurs 4 to 8 hours after allergen exposure and is characterized by congestion, fatigue, malaise, irritability, and possibly neurocognitive deficits. The key to diagnosis of AR is awareness of signs and symptoms. IgE antibody tests to detect specific allergens are the standard method used today; however, in addition, diagnosis must be confirmed with a positive history and demonstration that the symptoms are the result of IgE-mediated inflammation.. allergic rhinitis| ige| mast cells| perennial rhinitis|practice parameters| nasal-mucosa| dust mite| asthma| childhood| disease| prevalence| cytokines| il-4."	JUL-2001	allergic rhinitis| ige| mast cells| perennial rhinitis|practice parameters| nasal-mucosa| dust mite| asthma| childhood| disease| prevalence| cytokines| il-4	Skoner, DR	Allergic rhinitis: Definition, epidemiology, detection, and pathophysiology, diagnosis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergic rhinitis; IgE; mast cells; perennial rhinitis	PRACTICE PARAMETERS; NASAL-MUCOSA; DUST MITE; ASTHMA; CHILDHOOD; DISEASE; PREVALENCE; CYTOKINES; IL-4	"Allergic rhinitis (AR) is a heterogeneous disorder that despite its high prevalence is often undiagnosed. It is characterized by one or more symptoms including sneezing, itching, nasal congestion, and rhinorrhea. Many causative agents have been linked to AR including pollens, molds, dust mites, and animal dander. Seasonal allergic rhinitis (SAR) is fairly easy to identify because of the rapid and reproducible onset and offset of symptoms in association with pollen exposure. Perennial AR is often more difficult to detect than SAR because of the overlap with sinusitis, respiratory infections, and vasomotor rhinitis. SAR can result in hyperresponsiveness to allergens such as cigarette smoke, once pollen season is over. Perennial AR is defined as occurring during approximately 9 months of the year. AR affects an estimated 20 to 40 million people in the United States alone, and the incidence is increasing; an estimated 20% of cases are SAR; 40% of cases are perennial rhinitis; and 40% of cases are mixed. The pathophysiology of SAR is complex. There is a strong genetic component to the allergic response, which is driven through mucosal infiltration and action on plasma cells, roast cells, and eosinophils. The allergic response occurs in two phases, which are considered the ""early"" and ""late"" phase responses. Early phase response occurs within minutes of exposure to the allergen and tends to produce sneezing, itching, and clear rhinorrhea; late phase response occurs 4 to 8 hours after allergen exposure and is characterized by congestion, fatigue, malaise, irritability, and possibly neurocognitive deficits. The key to diagnosis of AR is awareness of signs and symptoms. IgE antibody tests to detect specific allergens are the standard method used today; however, in addition, diagnosis must be confirmed with a positive history and demonstration that the symptoms are the result of IgE-mediated inflammation."	39	329	2001	7	10.1067/mai.2001.115569	Allergy; Immunology
Emissions of metals associated with motor vehicle roadways. Emissions of metals and other particle-phase species from on-road motor vehicles were measured in two tunnels in Milwaukee, WI during the summer of 2000 and winter of 2001. Emission factors were calculated from measurements of fine (PM2.5) and coarse (PM10) particulate matter at tunnel entrances and exits, and effects of fleet composition and season were investigated. Cascade impactors (MOUDI) were used to obtain size-resolved metal emission rates. Metals were quantified with inductively-coupled plasma mass spectrometry (ICP-MS) and X-ray fluorescence (XRF). PM10 emission rates ranged from 38.7 to 201 mg km(-1) and were composed mainly of organic carbon (OC, 30%), inorganic ions (sulfate, chloride, nitrate, ammonium, 20%), metals (19%), and elemental carbon (EC, 9.3%). PM10 metal emissions were dominated by crustal elements Si, Fe, Ca, Na, Mg, Al, and K, and elements associated with tailpipe emissions and brake and tire wear, including Cu, Zn, Sb, Ba, Pb, and S. Metals emitted in PM2.5 were lower (11.6% of mass). Resuspension of roadway dust was dependent on weather and road surface conditions, and increased emissions were related to higher traffic volumes and fractions of heavy trucks. Emission of noble metals from catalytic converters appeared to be impacted by the presence of older vehicles. Elements related to brake wear were impacted by enriched road dust resuspension, but correlations between these elements in PM2.5 indicate that direct brake wear emissions are also important. A submicrometer particle mode was observed in the emissions of Pb, Ca, Fe, and Cu.. airborne particulate matter| fine organic aerosol| chemical-composition| source profiles| los-angeles| urban areas| exhaust| tunnel| asthma| carbon.	FEB 1-2005	airborne particulate matter| fine organic aerosol| chemical-composition| source profiles| los-angeles| urban areas| exhaust| tunnel| asthma| carbon	Lough, GC; Schauer, JJ; Park, JS; Shafer, MM; Deminter, JT; Weinstein, JP	Emissions of metals associated with motor vehicle roadways		ENVIRONMENTAL SCIENCE & TECHNOLOGY		AIRBORNE PARTICULATE MATTER; FINE ORGANIC AEROSOL; CHEMICAL-COMPOSITION; SOURCE PROFILES; LOS-ANGELES; URBAN AREAS; EXHAUST; TUNNEL; ASTHMA; CARBON	Emissions of metals and other particle-phase species from on-road motor vehicles were measured in two tunnels in Milwaukee, WI during the summer of 2000 and winter of 2001. Emission factors were calculated from measurements of fine (PM2.5) and coarse (PM10) particulate matter at tunnel entrances and exits, and effects of fleet composition and season were investigated. Cascade impactors (MOUDI) were used to obtain size-resolved metal emission rates. Metals were quantified with inductively-coupled plasma mass spectrometry (ICP-MS) and X-ray fluorescence (XRF). PM10 emission rates ranged from 38.7 to 201 mg km(-1) and were composed mainly of organic carbon (OC, 30%), inorganic ions (sulfate, chloride, nitrate, ammonium, 20%), metals (19%), and elemental carbon (EC, 9.3%). PM10 metal emissions were dominated by crustal elements Si, Fe, Ca, Na, Mg, Al, and K, and elements associated with tailpipe emissions and brake and tire wear, including Cu, Zn, Sb, Ba, Pb, and S. Metals emitted in PM2.5 were lower (11.6% of mass). Resuspension of roadway dust was dependent on weather and road surface conditions, and increased emissions were related to higher traffic volumes and fractions of heavy trucks. Emission of noble metals from catalytic converters appeared to be impacted by the presence of older vehicles. Elements related to brake wear were impacted by enriched road dust resuspension, but correlations between these elements in PM2.5 indicate that direct brake wear emissions are also important. A submicrometer particle mode was observed in the emissions of Pb, Ca, Fe, and Cu.	52	327	2005	11	10.1021/es048715f	Engineering; Environmental Sciences & Ecology
Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Commensal microflora (normal microflora, indigenous microbiota) consists of those micro-organisms, which are present on body surfaces covered by epithelial cells and are exposed to the external environment (gastrointestinal and respiratory tract, vagina, skin, etc.). The number of bacteria colonising mucosal and skin surfaces exceeds the number of cells forming human body. Commensal bacteria co-evolved with their hosts, however, under specific conditions they are able to overcome protective host responses and exert pathologic effects. Resident bacteria form complex ecosystems, whose diversity is enormous. The most abundant microflora. is present in the distal parts of the gut; the majority of the intestinal bacteria are Gram-negative anaerobes. More than 50% of intestinal bacteria cannot be cultured by conventional microbiological techniques. Molecular biological methods help in analysing the structural and functional complexity of the microflora and in identifying its components. Resident microflora contains a number of components able to activate innate and adaptive immunity. Unlimited immune activation in response to signals from commensal bacteria could pose the risk of inflammation; immune responses to mucosal microbiota therefore require a precise regulatory control. The mucosal immune system has developed specialised regulatory, anti-inflammatory mechanisms for eliminating or tolerating non-dangerous, food and airborne antigens and commensal micro-organisms (oral, mucosal tolerance). However, at the same time the mucosal immune system must provide local defense mechanisms against environmental threats (e.g. invading pathogens). This important requirement is fulfilled by several mechanisms of mucosal immunity: strongly developed innate defense mechanisms ensuring appropriate function of the mucosal barrier, existence of unique types of lymphocytes and their products, transport of polymeric immunoglobulins through epithelial cells into secretions (slgA) and migration and homing of cells originating from the mucosal organised tissues in mucosae and exocrine glands. The important role of commensal bacteria in development of optimally functioning mucosal immune system was demonstrated in germ-free animals (using gnotobiological techniques). Involvement of commensal microflora and its components with strong immunoactivating properties (e.g. LPS, peptidoglycans, superantigens, bacterial DNA, Hsp) in etiopathogenetic mechanism of various complex, multifactorial and multigenic diseases, including inflammatory bowel diseases, periodontal disease, rheumatoid arthritis, atherosclerosis, allergy, multiorgan failure, colon cancer has been recently suggested. Animal models of human diseases reared in defined gnotobiotic conditions are helping to elucidate the aetiology of these frequent disorders. An improved understanding of commensal bacteria-host interactions employing germ-free animal models with selective colonisation strategies combined with modern molecular techniques could bring new insights into the mechanisms of mucosal immunity and also into pathogenetic mechanisms of several infectious, inflammatory, autoimmune and neoplastic diseases. Regulation of microflora composition (e.g. by probiotics and prebiotics) offers the possibility to influence the development of mucosal and systemic immunity but it can play a role also in prevention and treatment of some diseases. (C) 2004 Elsevier B.V. All rights reserved.. mucosal microbiota| intestinal barrier| germ-free animal| gut inflammation| allergy| autoimmunity| probioties|germ-free piglets| intestinal epithelial-cells| probiotic escherichia-coli| innate immunity| gastrointestinal microflora| conventional conditions| antibody-formation| molecular mimicry| balb/c mice| cpg-dna.	MAY 15-2004	mucosal microbiota| intestinal barrier| germ-free animal| gut inflammation| allergy| autoimmunity| probioties|germ-free piglets| intestinal epithelial-cells| probiotic escherichia-coli| innate immunity| gastrointestinal microflora| conventional conditions| antibody-formation| molecular mimicry| balb/c mice| cpg-dna	Tlaskalova-Hogenova, H; Stepankova, R; Hudcovic, T; Tuckova, L; Cukrowska, B; Lodinova-Zadnikova, R; Kozakova, H; Rossmann, P; Bartova, J; Sokol, D; Funda, DP; Borovska, D; Rehakova, Z; Sinkora, J; Hofman, J; Drastich, P; Kokesova, A	Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases		IMMUNOLOGY LETTERS	mucosal microbiota; intestinal barrier; germ-free animal; gut inflammation; allergy; autoimmunity; probioties	GERM-FREE PIGLETS; INTESTINAL EPITHELIAL-CELLS; PROBIOTIC ESCHERICHIA-COLI; INNATE IMMUNITY; GASTROINTESTINAL MICROFLORA; CONVENTIONAL CONDITIONS; ANTIBODY-FORMATION; MOLECULAR MIMICRY; BALB/C MICE; CPG-DNA	Commensal microflora (normal microflora, indigenous microbiota) consists of those micro-organisms, which are present on body surfaces covered by epithelial cells and are exposed to the external environment (gastrointestinal and respiratory tract, vagina, skin, etc.). The number of bacteria colonising mucosal and skin surfaces exceeds the number of cells forming human body. Commensal bacteria co-evolved with their hosts, however, under specific conditions they are able to overcome protective host responses and exert pathologic effects. Resident bacteria form complex ecosystems, whose diversity is enormous. The most abundant microflora. is present in the distal parts of the gut; the majority of the intestinal bacteria are Gram-negative anaerobes. More than 50% of intestinal bacteria cannot be cultured by conventional microbiological techniques. Molecular biological methods help in analysing the structural and functional complexity of the microflora and in identifying its components. Resident microflora contains a number of components able to activate innate and adaptive immunity. Unlimited immune activation in response to signals from commensal bacteria could pose the risk of inflammation; immune responses to mucosal microbiota therefore require a precise regulatory control. The mucosal immune system has developed specialised regulatory, anti-inflammatory mechanisms for eliminating or tolerating non-dangerous, food and airborne antigens and commensal micro-organisms (oral, mucosal tolerance). However, at the same time the mucosal immune system must provide local defense mechanisms against environmental threats (e.g. invading pathogens). This important requirement is fulfilled by several mechanisms of mucosal immunity: strongly developed innate defense mechanisms ensuring appropriate function of the mucosal barrier, existence of unique types of lymphocytes and their products, transport of polymeric immunoglobulins through epithelial cells into secretions (slgA) and migration and homing of cells originating from the mucosal organised tissues in mucosae and exocrine glands. The important role of commensal bacteria in development of optimally functioning mucosal immune system was demonstrated in germ-free animals (using gnotobiological techniques). Involvement of commensal microflora and its components with strong immunoactivating properties (e.g. LPS, peptidoglycans, superantigens, bacterial DNA, Hsp) in etiopathogenetic mechanism of various complex, multifactorial and multigenic diseases, including inflammatory bowel diseases, periodontal disease, rheumatoid arthritis, atherosclerosis, allergy, multiorgan failure, colon cancer has been recently suggested. Animal models of human diseases reared in defined gnotobiotic conditions are helping to elucidate the aetiology of these frequent disorders. An improved understanding of commensal bacteria-host interactions employing germ-free animal models with selective colonisation strategies combined with modern molecular techniques could bring new insights into the mechanisms of mucosal immunity and also into pathogenetic mechanisms of several infectious, inflammatory, autoimmune and neoplastic diseases. Regulation of microflora composition (e.g. by probiotics and prebiotics) offers the possibility to influence the development of mucosal and systemic immunity but it can play a role also in prevention and treatment of some diseases. (C) 2004 Elsevier B.V. All rights reserved.	91	326	2004	12	10.1016/j.imlet.2004.02.005	Immunology
Indoor air quality, ventilation and health symptoms in schools: an analysis of existing information. We reviewed the literature on Indoor Air Quality (IAQ), ventilation, and building-related health problems in schools and identified commonly reported building-related health symptoms involving schools until 1999. We collected existing data on ventilation rates, carbon dioxide (CO(2) ) concentrations and symptom-relevant indoor air contaminants, and evaluated information on causal relationships between pollutant exposures and health symptoms. Reported ventilation and CO(2) data strongly indicate that ventilation is inadequate in many classrooms, possibly leading to health symptoms. Adequate ventilation should be a major focus of design or remediation efforts. Total volatile organic compounds, formaldehyde (HCHO) and microbiological contaminants are reported. Low HCHO concentrations were unlikely to cause acute irritant symptoms (<0.05 ppm), but possibly increased risks for allergen sensitivities, chronic irritation, and cancer. Reported microbiological contaminants included allergens in deposited dust, fungi, and bacteria. Levels of specific allergens were sufficient to cause symptoms in allergic occupants. Measurements of airborne bacteria and airborne and surface fungal spores were reported in schoolrooms. Asthma and 'sick building syndrome' symptoms are commonly reported. The few studies investigating causal relationships between health symptoms and exposures to specific pollutants suggest that such symptoms in schools are related to exposures to volatile organic compounds (VOCs), molds and microbial VOCs, and allergens.. allergy| asthma| microbiological contaminant| carbon dioxide concentration| formaldehyde| sick building syndrome| ventilation rate|volatile organic-compounds| building syndrome symptoms| day-care-centers| der-p-i| fel-d-i| respiratory symptoms| co2 concentrations| smooth floors| dust| children.	MAR-2003	allergy| asthma| microbiological contaminant| carbon dioxide concentration| formaldehyde| sick building syndrome| ventilation rate|volatile organic-compounds| building syndrome symptoms| day-care-centers| der-p-i| fel-d-i| respiratory symptoms| co2 concentrations| smooth floors| dust| children	Daisey, JM; Angell, WJ; Apte, MG	Indoor air quality, ventilation and health symptoms in schools: an analysis of existing information		INDOOR AIR	allergy; asthma; microbiological contaminant; carbon dioxide concentration; formaldehyde; sick building syndrome; ventilation rate	VOLATILE ORGANIC-COMPOUNDS; BUILDING SYNDROME SYMPTOMS; DAY-CARE-CENTERS; DER-P-I; FEL-D-I; RESPIRATORY SYMPTOMS; CO2 CONCENTRATIONS; SMOOTH FLOORS; DUST; CHILDREN	We reviewed the literature on Indoor Air Quality (IAQ), ventilation, and building-related health problems in schools and identified commonly reported building-related health symptoms involving schools until 1999. We collected existing data on ventilation rates, carbon dioxide (CO(2) ) concentrations and symptom-relevant indoor air contaminants, and evaluated information on causal relationships between pollutant exposures and health symptoms. Reported ventilation and CO(2) data strongly indicate that ventilation is inadequate in many classrooms, possibly leading to health symptoms. Adequate ventilation should be a major focus of design or remediation efforts. Total volatile organic compounds, formaldehyde (HCHO) and microbiological contaminants are reported. Low HCHO concentrations were unlikely to cause acute irritant symptoms (<0.05 ppm), but possibly increased risks for allergen sensitivities, chronic irritation, and cancer. Reported microbiological contaminants included allergens in deposited dust, fungi, and bacteria. Levels of specific allergens were sufficient to cause symptoms in allergic occupants. Measurements of airborne bacteria and airborne and surface fungal spores were reported in schoolrooms. Asthma and 'sick building syndrome' symptoms are commonly reported. The few studies investigating causal relationships between health symptoms and exposures to specific pollutants suggest that such symptoms in schools are related to exposures to volatile organic compounds (VOCs), molds and microbial VOCs, and allergens.	65	324	2003	12	10.1034/j.1600-0668.2003.00153.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. In the study of complex traits, the utility of linkage analysis and single marker association tests can be limited for researchers attempting to elucidate the complex interplay between a gene and environmental covariates. For these purposes, tests of gene-environment interactions are needed. In addition, recent studies have indicated that haplotypes, which are specific combinations of nucleotides on the same chromosome, may be more suitable as the unit of analysis for statistical tests than single genetic markers. The difficulty with this approach is that, in standard laboratory genotyping, haplotypes are often not directly observable. Instead, unphased marker phenotypes are collected. In this article, we present a method for estimating and testing haplotype-environment interactions when linkage phase is potentially ambiguous. The method builds on the work of Schaid et al. [2002] and is applicable to any trait that can be placed in the generalized linear model framework. Simulations were run to illustrate the salient features of the method. addition, the method was used to test for haplotype-smoking exposure interaction with data from the Childhood Asthma Management Program. Copyright (C) 2003 S. Karger AG, Basel.. haplotype| association| gene-environment interaction| generalized linear model|em algorithm| maximum-likelihood| genomic control| incomplete data| gene promoter| interleukin-10| association| population| asthma| polymorphisms.	2003	haplotype| association| gene-environment interaction| generalized linear model|em algorithm| maximum-likelihood| genomic control| incomplete data| gene promoter| interleukin-10| association| population| asthma| polymorphisms	Lake, SL; Lyon, H; Tantisira, K; Silverman, EK; Weiss, ST; Laird, NM; Schaid, DJ	Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous		HUMAN HEREDITY	haplotype; association; gene-environment interaction; generalized linear model	EM ALGORITHM; MAXIMUM-LIKELIHOOD; GENOMIC CONTROL; INCOMPLETE DATA; GENE PROMOTER; INTERLEUKIN-10; ASSOCIATION; POPULATION; ASTHMA; POLYMORPHISMS	In the study of complex traits, the utility of linkage analysis and single marker association tests can be limited for researchers attempting to elucidate the complex interplay between a gene and environmental covariates. For these purposes, tests of gene-environment interactions are needed. In addition, recent studies have indicated that haplotypes, which are specific combinations of nucleotides on the same chromosome, may be more suitable as the unit of analysis for statistical tests than single genetic markers. The difficulty with this approach is that, in standard laboratory genotyping, haplotypes are often not directly observable. Instead, unphased marker phenotypes are collected. In this article, we present a method for estimating and testing haplotype-environment interactions when linkage phase is potentially ambiguous. The method builds on the work of Schaid et al. [2002] and is applicable to any trait that can be placed in the generalized linear model framework. Simulations were run to illustrate the salient features of the method. addition, the method was used to test for haplotype-smoking exposure interaction with data from the Childhood Asthma Management Program. Copyright (C) 2003 S. Karger AG, Basel.	41	323	2003	10	10.1159/000071811	Genetics & Heredity
Impact of respiratory virus infections on persons with chronic underlying conditions. Context While hospitalization rates have declined overall, hospitalizations for acute lower respiratory tract infections have increased steadily since 1980. Development of new approaches for prevention of acute respiratory tract conditions requires studies of the etiologies of infections and quantification of the risk of hospitalization for vulnerable patients. Objective To determine the frequency of specific virus infections associated with acute respiratory tract conditions leading to hospitalization of chronically ill patients. Design Analysis of viral etiology of patients hospitalized with acute respiratory tract conditions between July 1991 and June 1995. Setting Four large clinics and related hospitals serving diverse populations representative of Harris County, Texas. Patients A total of 1029 patients who were hospitalized for pneumonia, tracheobronchitis, bronchiolitis, croup, exacerbations of asthma or chronic obstructive pulmonary disease, and/or congestive heart failure. Main Outcome Measure Virus infection, defined by culture, antigen detection, and significant rise in serum antibodies, by underlying condition; hospitalization rates by low- vs middle-income status. Results Ninety-three percent of patients older than 5 years had a chronic underlying condition; a chronic pulmonary condition was most common. Patients with chronic pulmonary disease from low-income populations were hospitalized at a rate of 398.6 per 10 000, almost 8 times higher than the rate for patients from middle-income groups (52.2 per 10 000; P<.001). Of the 403 patients (44.4% of adults and 32.3% of children) who submitted convalescent serum specimens for antibody testing, respiratory tract virus infections were detected in 181 (44.9%). influenza, parainfluenza, and respiratory syncytial virus (RSV) infections accounted for 75% of all virus infections. Conclusions Our study suggests that respiratory virus infections commonly trigger serious acute respiratory conditions that result in hospitalization of patients with chronic underlying conditions, highlighting the need for development of effective vaccines for these viruses, especially for parainfluenza and RSV.. syncytial virus| air-pollution| disease hospitalizations| influenza epidemics| viral-infections| asthma| children| adults| illness| vaccine.	JAN 26-2000	syncytial virus| air-pollution| disease hospitalizations| influenza epidemics| viral-infections| asthma| children| adults| illness| vaccine	Glezen, WP; Greenberg, SB; Atmar, RL; Piedra, PA; Couch, RB	Impact of respiratory virus infections on persons with chronic underlying conditions		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		SYNCYTIAL VIRUS; AIR-POLLUTION; DISEASE HOSPITALIZATIONS; INFLUENZA EPIDEMICS; VIRAL-INFECTIONS; ASTHMA; CHILDREN; ADULTS; ILLNESS; VACCINE	Context While hospitalization rates have declined overall, hospitalizations for acute lower respiratory tract infections have increased steadily since 1980. Development of new approaches for prevention of acute respiratory tract conditions requires studies of the etiologies of infections and quantification of the risk of hospitalization for vulnerable patients. Objective To determine the frequency of specific virus infections associated with acute respiratory tract conditions leading to hospitalization of chronically ill patients. Design Analysis of viral etiology of patients hospitalized with acute respiratory tract conditions between July 1991 and June 1995. Setting Four large clinics and related hospitals serving diverse populations representative of Harris County, Texas. Patients A total of 1029 patients who were hospitalized for pneumonia, tracheobronchitis, bronchiolitis, croup, exacerbations of asthma or chronic obstructive pulmonary disease, and/or congestive heart failure. Main Outcome Measure Virus infection, defined by culture, antigen detection, and significant rise in serum antibodies, by underlying condition; hospitalization rates by low- vs middle-income status. Results Ninety-three percent of patients older than 5 years had a chronic underlying condition; a chronic pulmonary condition was most common. Patients with chronic pulmonary disease from low-income populations were hospitalized at a rate of 398.6 per 10 000, almost 8 times higher than the rate for patients from middle-income groups (52.2 per 10 000; P<.001). Of the 403 patients (44.4% of adults and 32.3% of children) who submitted convalescent serum specimens for antibody testing, respiratory tract virus infections were detected in 181 (44.9%). influenza, parainfluenza, and respiratory syncytial virus (RSV) infections accounted for 75% of all virus infections. Conclusions Our study suggests that respiratory virus infections commonly trigger serious acute respiratory conditions that result in hospitalization of patients with chronic underlying conditions, highlighting the need for development of effective vaccines for these viruses, especially for parainfluenza and RSV.	42	323	2000	7	10.1001/jama.283.4.499	General & Internal Medicine
Non-eosinophilic asthma: importance and possible mechanisms. There is increasing evidence that inflammatory mechanisms other than eosinophilic inflammation may be involved in producing the final common pathway of enhanced bronchial reactivity and reversible airflow obstruction that characterises asthma. A review of the literature has shown that, at most, only 50% of asthma cases are attributable to eosinophilic airway inflammation. It is hypothesised that a major proportion of asthma is based on neutrophilic airway inflammation, possibly triggered by environmental exposure to bacterial endotoxin, particulate air pollution, and ozone, as well as viral infections. If there are indeed two (or more) subtypes of asthma, and if non-eosinophilic (neutrophil mediated) asthma is relatively common, this would have major consequences for the treatment and prevention of asthma since most treatment and prevention strategies are now almost entirely focused on allergic/eosinophilic asthma and allergen avoidance measures, respectively. It is therefore important to study the aetiology of asthma further, including the underlying inflammatory profiles.. anti-ige antibody| particulate air-pollution| house-dust endotoxin| induced sputum| neutrophilic inflammation| ambient ozone| bronchial hyperreactivity| inhaled corticosteroids| monoclonal-antibody| occupational asthma.	JUL-2002	anti-ige antibody| particulate air-pollution| house-dust endotoxin| induced sputum| neutrophilic inflammation| ambient ozone| bronchial hyperreactivity| inhaled corticosteroids| monoclonal-antibody| occupational asthma	Douwes, J; Gibson, P; Pekkanen, J; Pearce, N	Non-eosinophilic asthma: importance and possible mechanisms		THORAX		ANTI-IGE ANTIBODY; PARTICULATE AIR-POLLUTION; HOUSE-DUST ENDOTOXIN; INDUCED SPUTUM; NEUTROPHILIC INFLAMMATION; AMBIENT OZONE; BRONCHIAL HYPERREACTIVITY; INHALED CORTICOSTEROIDS; MONOCLONAL-ANTIBODY; OCCUPATIONAL ASTHMA	There is increasing evidence that inflammatory mechanisms other than eosinophilic inflammation may be involved in producing the final common pathway of enhanced bronchial reactivity and reversible airflow obstruction that characterises asthma. A review of the literature has shown that, at most, only 50% of asthma cases are attributable to eosinophilic airway inflammation. It is hypothesised that a major proportion of asthma is based on neutrophilic airway inflammation, possibly triggered by environmental exposure to bacterial endotoxin, particulate air pollution, and ozone, as well as viral infections. If there are indeed two (or more) subtypes of asthma, and if non-eosinophilic (neutrophil mediated) asthma is relatively common, this would have major consequences for the treatment and prevention of asthma since most treatment and prevention strategies are now almost entirely focused on allergic/eosinophilic asthma and allergen avoidance measures, respectively. It is therefore important to study the aetiology of asthma further, including the underlying inflammatory profiles.	97	315	2002	6	10.1136/thorax.57.7.643	Respiratory System
Traffic, susceptibility, and childhood asthma. Results from studies of traffic and childhood asthma have been inconsistent, but there has been little systematic evaluation of susceptible subgroups. In this study, we examined the relationship of local traffic-related exposure and asthma and wheeze in southern California school children (5-7 years of age). Lifetime history of doctor-diagnosed asthma and prevalent asthma and wheeze were evaluated by questionnaire. Parental history of asthma and child's history of allergic symptoms, sex, and early-life exposure (residence at the same home since 2 years of age) were examined as susceptibility factors. Residential exposure was assessed by proximity to a major road and by modeling exposure to local traffic-related pollutants. Residence within 75 in of a major road was associated with an increased risk of lifetime asthma [odds ratio (OR) = 1.29; 95% confidence interval (CI), 1.01-1.86], prevalent asthma (OR = 1.50; 95% Cl, 1.16-1-95), and wheeze (OR = 1.40; 95% Cl, 1.09-1-78). Susceptibility increased in long-term residents with no parental history of asthma for lifetime asthma (OR = 1.85; 95% Cl, 1. 11-3.09), prevalent asthma (OR = 2.46; 95% Cl, 0.48-4.09), and recent wheeze (OR = 2.74; 95% Cl, 1.71-4-39). The higher risk of asthma near a major road decreased to background rates at 150-200 in from the road. In children with a parental history of asthma and in children moving to the residence after 2 years of age, there was no increased risk associated with exposure. Effect of residential proximity to roadways was also larger in girls. A similar pattern of effects was observed with traffic-modeled exposure. These results indicate that residence near a major road is associated with asthma. The reason for larger effects in those with no parental history of asthma merits further investigation.. air pollution| asthma| child| epidemiology| traffic|environmental tobacco-smoke| chronic respiratory symptoms| ambient nitrogen-dioxide| air-pollution| wheezing illness| parental smoking| maternal smoking| school-children| major highway| exposure.	MAY-2006	air pollution| asthma| child| epidemiology| traffic|environmental tobacco-smoke| chronic respiratory symptoms| ambient nitrogen-dioxide| air-pollution| wheezing illness| parental smoking| maternal smoking| school-children| major highway| exposure	McConnell, R; Berhane, K; Yao, L; Jerrett, M; Lurmann, F; Gilliland, F; Kunzli, N; Gauderman, J; Avol, E; Thomas, D; Peters, J	Traffic, susceptibility, and childhood asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma; child; epidemiology; traffic	ENVIRONMENTAL TOBACCO-SMOKE; CHRONIC RESPIRATORY SYMPTOMS; AMBIENT NITROGEN-DIOXIDE; AIR-POLLUTION; WHEEZING ILLNESS; PARENTAL SMOKING; MATERNAL SMOKING; SCHOOL-CHILDREN; MAJOR HIGHWAY; EXPOSURE	Results from studies of traffic and childhood asthma have been inconsistent, but there has been little systematic evaluation of susceptible subgroups. In this study, we examined the relationship of local traffic-related exposure and asthma and wheeze in southern California school children (5-7 years of age). Lifetime history of doctor-diagnosed asthma and prevalent asthma and wheeze were evaluated by questionnaire. Parental history of asthma and child's history of allergic symptoms, sex, and early-life exposure (residence at the same home since 2 years of age) were examined as susceptibility factors. Residential exposure was assessed by proximity to a major road and by modeling exposure to local traffic-related pollutants. Residence within 75 in of a major road was associated with an increased risk of lifetime asthma [odds ratio (OR) = 1.29; 95% confidence interval (CI), 1.01-1.86], prevalent asthma (OR = 1.50; 95% Cl, 1.16-1-95), and wheeze (OR = 1.40; 95% Cl, 1.09-1-78). Susceptibility increased in long-term residents with no parental history of asthma for lifetime asthma (OR = 1.85; 95% Cl, 1. 11-3.09), prevalent asthma (OR = 2.46; 95% Cl, 0.48-4.09), and recent wheeze (OR = 2.74; 95% Cl, 1.71-4-39). The higher risk of asthma near a major road decreased to background rates at 150-200 in from the road. In children with a parental history of asthma and in children moving to the residence after 2 years of age, there was no increased risk associated with exposure. Effect of residential proximity to roadways was also larger in girls. A similar pattern of effects was observed with traffic-modeled exposure. These results indicate that residence near a major road is associated with asthma. The reason for larger effects in those with no parental history of asthma merits further investigation.	52	314	2006	7	10.1289/ehp.8594	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder. (J Allergy Clin Immunol 2004;114:S51-131.). aae| acquired angioedema| angioedema| c1 esterase inhibitor| c1-inh| hae| hane| hano| hereditary angioedema| hereditary angioneurotic edema| angioneurotic edema| chemically induced angioedema| human serping1 protein|hormone replacement therapy| molecular-weight kininogen| factor-viii concentrate| factor factor-xii| converting-enzyme-activity| ovarian follicular-fluid| plasma kallikrein/kinin system| helicobacter-pylori infection| normal c1-inhibitor activity| epsilon aminocaproic acid.	2004	aae| acquired angioedema| angioedema| c1 esterase inhibitor| c1-inh| hae| hane| hano| hereditary angioedema| hereditary angioneurotic edema| angioneurotic edema| chemically induced angioedema| human serping1 protein|hormone replacement therapy| molecular-weight kininogen| factor-viii concentrate| factor factor-xii| converting-enzyme-activity| ovarian follicular-fluid| plasma kallikrein/kinin system| helicobacter-pylori infection| normal c1-inhibitor activity| epsilon aminocaproic acid	Agostoni, A; Aygoren-Pursun, E; Binkley, KE; Blanch, A; Bork, K; Bouillet, L; Bucher, C; Castaldo, AJ; Cicardi, M; Davis, AE; De Carolis, C; Drouet, C; Duponchel, C; Farkas, H; Fay, K; Fekete, B; Fischer, B; Fontana, L; Fust, G; Giacomelli, R; Groner, A; Hack, CE; Harmat, G; Jakenfelds, J; Juers, M; Kalmar, L; Kaposi, PN; Karadi, I; Kitzinger, A; Kollar, T; Kreuz, W; Lakatos, P; Longhurst, HJ; Lopez-Trascasa, M; Martinez-Saguer, I; Monnier, N; Nagy, I; Nemeth, E; Nielsen, EW; Nuijens, JH; O'Grady, C; Pappalardo, E; Penna, V; Perricone, C; Perricone, R; Rauch, U; Roche, O; Rusicke, E; Spath, PJ; Szendei, G; Takacs, E; Tordai, A; Truedsson, L; Varga, L; Visy, B; Williams, K; Zanichelli, A; Zingale, L	Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	AAE; acquired angioedema; angioedema; C1 esterase inhibitor; C1-INH; HAE; HANE; HANO; hereditary angioedema; hereditary angioneurotic edema; angioneurotic edema; chemically induced angioedema; human SERPING1 protein	HORMONE REPLACEMENT THERAPY; MOLECULAR-WEIGHT KININOGEN; FACTOR-VIII CONCENTRATE; FACTOR FACTOR-XII; CONVERTING-ENZYME-ACTIVITY; OVARIAN FOLLICULAR-FLUID; PLASMA KALLIKREIN/KININ SYSTEM; HELICOBACTER-PYLORI INFECTION; NORMAL C1-INHIBITOR ACTIVITY; EPSILON AMINOCAPROIC ACID	Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder. (J Allergy Clin Immunol 2004;114:S51-131.)	456	312	2004	81	10.1016/j.jaci.2004.06.047	Allergy; Immunology
Housing and health: Time again for public health action. Poor housing conditions are associated with a wide range of health conditions, including respiratory infections, asthma. lead poisoning. injuries, and mental health. Addressing housing issues offers public health practitioners an opportunity to address an important social determinant of health. Public health has long been involved in housing issues, In the 19th century. health officials targeted poor sanitation, crowding, and inadequate ventilation to reduce infectious diseases as well as fire hazards to decrease injuries, Today, public health departments can employ multiple strategies to improve housing, such as developing and enforcing housing guidelines and codes, implementing ''Healthy Homes'' programs to improve indoor environmental quality, assessing housing conditions, and advocating for healthy, affordable housing, Now is the time for public health to create healthier homes by confronting substandard housing.. inner-city children| risk-factors| socioeconomic-status| tuberculosis infection| bronchial obstruction| environmental-control| respiratory symptoms| homeless children| impact assessment| alameda-county.	MAY-2002	inner-city children| risk-factors| socioeconomic-status| tuberculosis infection| bronchial obstruction| environmental-control| respiratory symptoms| homeless children| impact assessment| alameda-county	Krieger, J; Higgins, DL	Housing and health: Time again for public health action		AMERICAN JOURNAL OF PUBLIC HEALTH		INNER-CITY CHILDREN; RISK-FACTORS; SOCIOECONOMIC-STATUS; TUBERCULOSIS INFECTION; BRONCHIAL OBSTRUCTION; ENVIRONMENTAL-CONTROL; RESPIRATORY SYMPTOMS; HOMELESS CHILDREN; IMPACT ASSESSMENT; ALAMEDA-COUNTY	Poor housing conditions are associated with a wide range of health conditions, including respiratory infections, asthma. lead poisoning. injuries, and mental health. Addressing housing issues offers public health practitioners an opportunity to address an important social determinant of health. Public health has long been involved in housing issues, In the 19th century. health officials targeted poor sanitation, crowding, and inadequate ventilation to reduce infectious diseases as well as fire hazards to decrease injuries, Today, public health departments can employ multiple strategies to improve housing, such as developing and enforcing housing guidelines and codes, implementing ''Healthy Homes'' programs to improve indoor environmental quality, assessing housing conditions, and advocating for healthy, affordable housing, Now is the time for public health to create healthier homes by confronting substandard housing.	153	311	2002	11	10.2105/AJPH.92.5.758	Public, Environmental & Occupational Health
Maternal vitamin D status during pregnancy and child outcomes. Objective: To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child. Design: Prospective study. Setting: Princess Anne Maternity Hospital, Southampton, UK. Subjects: A group of 596 pregnant women were recruited. A total of 466 (78%) children were examined at birth, 440 (74%) at age 9 months and 178 (30%) at age 9 years. Methods: Maternal 25 (OH)-vitamin D concentrations were measured in late pregnancy. Anthropometry of the child was recorded at birth, 9 months and 9 years. At 9 months, atopic eczema was assessed. At 9 years, children had an echocardiogram and a dual energy x-ray absorptiometry scan, blood pressure, arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed. Results: There were no associations between maternal 25(OH)-vitamin D concentrations and the child's body size or measures of the child's intelligence, psychological health or cardiovascular system. Children whose mothers had a 25(OH)-vitamin D concentration in pregnancy 475 nmol/l had an increased risk of eczema on examination at 9 months (OR 3.26, 95% CI 1.15-9.29, P=0.025) and asthma at age 9 years (OR 5.40, 95% CI, 1.09-26.65, P=0.038) compared to children whose mothers had a concentration of <30 nmol/l. Conclusion: Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the child's intelligence, psychological health or cardiovascular system; there could be an increased risk of atopic disorders, but this needs confirmation in other studies. Sponsorship: The study was supported by the Medical Research Council and WellChild (previously known as Children Nationwide).. pregnancy| diet| vitamin d| infant| child|d deficiency| d supplementation| hypovitaminosis-d| fetal growth| asian women| bone mass| weight| prevalence| nutrition| asthma.	JAN-2008	pregnancy| diet| vitamin d| infant| child|d deficiency| d supplementation| hypovitaminosis-d| fetal growth| asian women| bone mass| weight| prevalence| nutrition| asthma	Gale, CR; Robinson, SM; Harvey, NC; Javaid, MK; Jiang, B; Martyn, CN; Godfrey, KM; Cooper, C	Maternal vitamin D status during pregnancy and child outcomes		EUROPEAN JOURNAL OF CLINICAL NUTRITION	pregnancy; diet; vitamin D; infant; child	D DEFICIENCY; D SUPPLEMENTATION; HYPOVITAMINOSIS-D; FETAL GROWTH; ASIAN WOMEN; BONE MASS; WEIGHT; PREVALENCE; NUTRITION; ASTHMA	Objective: To investigate whether exposure to high maternal concentrations of 25(OH)-vitamin D in pregnancy poses any risk to the child. Design: Prospective study. Setting: Princess Anne Maternity Hospital, Southampton, UK. Subjects: A group of 596 pregnant women were recruited. A total of 466 (78%) children were examined at birth, 440 (74%) at age 9 months and 178 (30%) at age 9 years. Methods: Maternal 25 (OH)-vitamin D concentrations were measured in late pregnancy. Anthropometry of the child was recorded at birth, 9 months and 9 years. At 9 months, atopic eczema was assessed. At 9 years, children had an echocardiogram and a dual energy x-ray absorptiometry scan, blood pressure, arterial compliance and carotid intima-media thickness were measured and intelligence and psychological function assessed. Results: There were no associations between maternal 25(OH)-vitamin D concentrations and the child's body size or measures of the child's intelligence, psychological health or cardiovascular system. Children whose mothers had a 25(OH)-vitamin D concentration in pregnancy 475 nmol/l had an increased risk of eczema on examination at 9 months (OR 3.26, 95% CI 1.15-9.29, P=0.025) and asthma at age 9 years (OR 5.40, 95% CI, 1.09-26.65, P=0.038) compared to children whose mothers had a concentration of <30 nmol/l. Conclusion: Exposure to maternal concentrations of 25(OH)-vitamin D in pregnancy in excess of 75 nmol/l does not appear to influence the child's intelligence, psychological health or cardiovascular system; there could be an increased risk of atopic disorders, but this needs confirmation in other studies. Sponsorship: The study was supported by the Medical Research Council and WellChild (previously known as Children Nationwide).	41	310	2008	10	10.1038/sj.ejcn.1602680	Nutrition & Dietetics
The role of selectins in inflammation and disease. Selectins are carbohydrate-binding molecules that bind to fucosylated and sialylated glycoprotein ligands, and are found on endothelial cells, leukocytes and platelets. They are involved in trafficking of cells of the innate immune system, T lymphocytes and platelets. An absence of selectins or selectin ligands has serious consequences in mice or humans, leading to recurrent bacterial infections and persistent disease. Selectins are involved in constitutive lymphocyte homing, and in chronic and acute inflammation processes, including post-ischemic inflammation in muscle, kidney and heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus. Selectin-neutralizing monoclonal antibodies, recombinant soluble P-selectin glycoprotein ligand 1 and small-molecule inhibitors of selectins have been tested in clinical trials on patients with multiple trauma, cardiac indications and pediatric asthma, respectively. Anti-selectin antibodies have also been successfully used in preclinical models to deliver imaging contrast agents and therapeutics to sites of inflammation. Further improvements in the efficiency, availability, specificity and pharmacokinetics of selectin inhibitors, and specialized application routes and schedules, hold promise for therapeutic indications.. adhesion-deficiency-ii| acute-renal-failure| double mutant mice| rolling in-vivo| p-selectin| leukocyte recruitment| apolipoprotein-e| endothelial adhesion| ischemia-reperfusion| activated platelets.	JUN-2003	adhesion-deficiency-ii| acute-renal-failure| double mutant mice| rolling in-vivo| p-selectin| leukocyte recruitment| apolipoprotein-e| endothelial adhesion| ischemia-reperfusion| activated platelets	Ley, K	The role of selectins in inflammation and disease		TRENDS IN MOLECULAR MEDICINE		ADHESION-DEFICIENCY-II; ACUTE-RENAL-FAILURE; DOUBLE MUTANT MICE; ROLLING IN-VIVO; P-SELECTIN; LEUKOCYTE RECRUITMENT; APOLIPOPROTEIN-E; ENDOTHELIAL ADHESION; ISCHEMIA-REPERFUSION; ACTIVATED PLATELETS	Selectins are carbohydrate-binding molecules that bind to fucosylated and sialylated glycoprotein ligands, and are found on endothelial cells, leukocytes and platelets. They are involved in trafficking of cells of the innate immune system, T lymphocytes and platelets. An absence of selectins or selectin ligands has serious consequences in mice or humans, leading to recurrent bacterial infections and persistent disease. Selectins are involved in constitutive lymphocyte homing, and in chronic and acute inflammation processes, including post-ischemic inflammation in muscle, kidney and heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus. Selectin-neutralizing monoclonal antibodies, recombinant soluble P-selectin glycoprotein ligand 1 and small-molecule inhibitors of selectins have been tested in clinical trials on patients with multiple trauma, cardiac indications and pediatric asthma, respectively. Anti-selectin antibodies have also been successfully used in preclinical models to deliver imaging contrast agents and therapeutics to sites of inflammation. Further improvements in the efficiency, availability, specificity and pharmacokinetics of selectin inhibitors, and specialized application routes and schedules, hold promise for therapeutic indications.	61	309	2003	6	10.1016/S1471-4914(03)00071-6	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Surface hydrophobin prevents immune recognition of airborne fungal spores. The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10 9 per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus(1-4). Although these conidia contain many antigens and allergens(5-7), it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (Delta rodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.. aspergillus-fumigatus| cell-wall| invasive aspergillosis| alveolar macrophages| cladosporium| responses| proteins| antigens| conidia| homes.	AUG 27-2009	aspergillus-fumigatus| cell-wall| invasive aspergillosis| alveolar macrophages| cladosporium| responses| proteins| antigens| conidia| homes	Aimanianda, V; Bayry, J; Bozza, S; Kniemeyer, O; Perruccio, K; Elluru, SR; Clavaud, C; Paris, S; Brakhage, AA; Kaveri, SV; Romani, L; Latge, JP	Surface hydrophobin prevents immune recognition of airborne fungal spores		NATURE		ASPERGILLUS-FUMIGATUS; CELL-WALL; INVASIVE ASPERGILLOSIS; ALVEOLAR MACROPHAGES; CLADOSPORIUM; RESPONSES; PROTEINS; ANTIGENS; CONIDIA; HOMES	The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10 9 per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus(1-4). Although these conidia contain many antigens and allergens(5-7), it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (Delta rodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.	30	307	2009	7	10.1038/nature08264	Science & Technology - Other Topics
Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Objective. This study examined the effects of daily and cumulative oral corticosteroid doses on the risk of fractures. Methods. Information was obtained from the General Practice Research Database, which contains medical records of general practitioners in England and Wales. The study included 244 235 oral corticosteroid users and 244 235 controls. Results. Patients taking higher doses (at least 7.5 mg daily of prednisolone or equivalent) had significantly increased risks of non-vertebral fracture [relative rate (RR) = 1.44, 95% confidence interval (CI) 1.34-1.54], hip fracture (RR = 2.21, 95% CI 1.85-2.64) and vertebral fracture (RR = 2.83, 95% CI 2.35-2.40) relative to patients using oral corticosteroids at lower doses (less than 2.5 mg per day). Fracture risk was also elevated among people with higher cumulative exposure to oral corticosteroids over the study period, but this effect was almost wholly removed by adjustment for daily dose, age, gender and other confounding variables. Conclusions. These findings suggest that the adverse skeletal effects of oral corticosteroids manifest rapidly and are related to daily dose. The level of previous exposure to oral corticosteroids was not a strong determinant of the risk of fracture. Preventive measures against corticosteroid-induced osteoporosis should therefore be instituted as soon after the commencement of glucocorticoid therapy as possible.. osteoporosis| epidemiology| glucocorticoids| fracture| risk factors|bone-mineral content| rheumatoid-arthritis| vertebral fractures| osteoporosis| therapy| uk| database| asthma.	DEC-2000	osteoporosis| epidemiology| glucocorticoids| fracture| risk factors|bone-mineral content| rheumatoid-arthritis| vertebral fractures| osteoporosis| therapy| uk| database| asthma	van Staa, TP; Leufkens, HGM; Abenhaim, L; Zhang, B; Cooper, C	Oral corticosteroids and fracture risk: relationship to daily and cumulative doses		RHEUMATOLOGY	osteoporosis; epidemiology; glucocorticoids; fracture; risk factors	BONE-MINERAL CONTENT; RHEUMATOID-ARTHRITIS; VERTEBRAL FRACTURES; OSTEOPOROSIS; THERAPY; UK; DATABASE; ASTHMA	Objective. This study examined the effects of daily and cumulative oral corticosteroid doses on the risk of fractures. Methods. Information was obtained from the General Practice Research Database, which contains medical records of general practitioners in England and Wales. The study included 244 235 oral corticosteroid users and 244 235 controls. Results. Patients taking higher doses (at least 7.5 mg daily of prednisolone or equivalent) had significantly increased risks of non-vertebral fracture [relative rate (RR) = 1.44, 95% confidence interval (CI) 1.34-1.54], hip fracture (RR = 2.21, 95% CI 1.85-2.64) and vertebral fracture (RR = 2.83, 95% CI 2.35-2.40) relative to patients using oral corticosteroids at lower doses (less than 2.5 mg per day). Fracture risk was also elevated among people with higher cumulative exposure to oral corticosteroids over the study period, but this effect was almost wholly removed by adjustment for daily dose, age, gender and other confounding variables. Conclusions. These findings suggest that the adverse skeletal effects of oral corticosteroids manifest rapidly and are related to daily dose. The level of previous exposure to oral corticosteroids was not a strong determinant of the risk of fracture. Preventive measures against corticosteroid-induced osteoporosis should therefore be instituted as soon after the commencement of glucocorticoid therapy as possible.	42	299	2000	7	10.1093/rheumatology/39.12.1383	Rheumatology
Serum Vitamin D Levels and Markers of Severity of Childhood Asthma in Costa Rica. Rationale: Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood. Objectives: To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. Methods: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses. Measurements and Main Results- Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log(10) unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% Cl, 0.05-0.67; P = 0.01), and increased airway responsiveness (a <= 8.58-mu mol provocative dose of methacholine producing a 20% fall in baseline FEV1 [OR, 0.15; 95% Cl, 0.024-0.97; P = 0.05]). Conclusions: Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.. 1,25-dihydroxyvitamin d-3| d deficiency| 25-hydroxyvitamin-d| epidemic| exposure| children| insights| reality| 25-hydroxycholecalciferol| radioimmunoassay.	MAY 1-2009	1,25-dihydroxyvitamin d-3| d deficiency| 25-hydroxyvitamin-d| epidemic| exposure| children| insights| reality| 25-hydroxycholecalciferol| radioimmunoassay	Brehm, JM; Celedon, JC; Soto-Quiros, ME; Avila, L; Hunninghake, GM; Forno, E; Laskey, D; Sylvia, JS; Hollis, BW; Weiss, ST; Litonjua, AA	Serum Vitamin D Levels and Markers of Severity of Childhood Asthma in Costa Rica		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		1,25-DIHYDROXYVITAMIN D-3; D DEFICIENCY; 25-HYDROXYVITAMIN-D; EPIDEMIC; EXPOSURE; CHILDREN; INSIGHTS; REALITY; 25-HYDROXYCHOLECALCIFEROL; RADIOIMMUNOASSAY	Rationale: Maternal vitamin D intake during pregnancy has been inversely associated with asthma symptoms in early childhood. However, no study has examined the relationship between measured vitamin D levels and markers of asthma severity in childhood. Objectives: To determine the relationship between measured vitamin D levels and both markers of asthma severity and allergy in childhood. Methods: We examined the relation between 25-hydroxyvitamin D levels (the major circulating form of vitamin D) and markers of allergy and asthma severity in a cross-sectional study of 616 Costa Rican children between the ages of 6 and 14 years. Linear, logistic, and negative binomial regressions were used for the univariate and multivariate analyses. Measurements and Main Results- Of the 616 children with asthma, 175 (28%) had insufficient levels of vitamin D (<30 ng/ml). In multivariate linear regression models, vitamin D levels were significantly and inversely associated with total IgE and eosinophil count. In multivariate logistic regression models, a log(10) unit increase in vitamin D levels was associated with reduced odds of any hospitalization in the previous year (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.004-0.71; P = 0.03), any use of antiinflammatory medications in the previous year (OR, 0.18; 95% Cl, 0.05-0.67; P = 0.01), and increased airway responsiveness (a <= 8.58-mu mol provocative dose of methacholine producing a 20% fall in baseline FEV1 [OR, 0.15; 95% Cl, 0.024-0.97; P = 0.05]). Conclusions: Our results suggest that vitamin D insufficiency is relatively frequent in an equatorial population of children with asthma. In these children, lower vitamin D levels are associated with increased markers of allergy and asthma severity.	42	297	2009	7	10.1164/rccm.200808-1361OC	General & Internal Medicine; Respiratory System
Treatment strategies for allergy and asthma. Allergic diseases have reached epidemic proportions worldwide. An understanding of the cellular and soluble mediators that are involved in allergic inflammatory responses not only helps in understanding the mechanisms of current treatments, but is also important for the identification of new targets that are amenable to both small-molecule and biological interventions. There is now considerable optimism with regards to tackling the allergy epidemic in light of improvements in systemic and mucosal allergen-specific immunotherapy, the identification of key cytokines and their receptors that drive T-helper-2-cell polarization, a clearer understanding of the pathways of leukocyte recruitment and the signalling pathways that are involved in cell activation and mediator secretion, and new approaches to vaccine development.. regulatory t-cells| house-dust mite| thymic stromal lymphopoietin| placebo-controlled trial| kinase inhibitor r112| smooth-muscle-cells| il-5 receptor-alpha| mast-cell| airway hyperresponsiveness| atopic-dermatitis.	MAR-2008	regulatory t-cells| house-dust mite| thymic stromal lymphopoietin| placebo-controlled trial| kinase inhibitor r112| smooth-muscle-cells| il-5 receptor-alpha| mast-cell| airway hyperresponsiveness| atopic-dermatitis	Holgate, ST; Polosao, R	Treatment strategies for allergy and asthma		NATURE REVIEWS IMMUNOLOGY		REGULATORY T-CELLS; HOUSE-DUST MITE; THYMIC STROMAL LYMPHOPOIETIN; PLACEBO-CONTROLLED TRIAL; KINASE INHIBITOR R112; SMOOTH-MUSCLE-CELLS; IL-5 RECEPTOR-ALPHA; MAST-CELL; AIRWAY HYPERRESPONSIVENESS; ATOPIC-DERMATITIS	Allergic diseases have reached epidemic proportions worldwide. An understanding of the cellular and soluble mediators that are involved in allergic inflammatory responses not only helps in understanding the mechanisms of current treatments, but is also important for the identification of new targets that are amenable to both small-molecule and biological interventions. There is now considerable optimism with regards to tackling the allergy epidemic in light of improvements in systemic and mucosal allergen-specific immunotherapy, the identification of key cytokines and their receptors that drive T-helper-2-cell polarization, a clearer understanding of the pathways of leukocyte recruitment and the signalling pathways that are involved in cell activation and mediator secretion, and new approaches to vaccine development.	174	296	2008	13	10.1038/nri2262	Immunology
Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children. The effects of maternal smoking during pregnancy and childhood environmental tobacco smoke (ETS) exposure on asthma and wheezing were investigated in 5,762 school-aged children residing in 12 Southern California communities. Responses to a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students were used to ascertain children with wheezing or physician-diagnosed asthma. Lifetime household exposures to tobacco smoke were assessed using responses about past and current smoking histories of household members and any history of maternal smoking during pregnancy. Logistic regression models were fitted to cross-sectional data to estimate the effects of in utero exposure to maternal smoking and previous and current ETS exposure on the prevalence of wheezing and physician-diagnosed asthma. In utero exposure to maternal smoking without subsequent postnatal ETS exposure was associated with increased prevalence of physician-diagnosed asthma (OR, 1.8; 95% CI, 1.1 to 2.9), asthma with current symptoms (OR, 2.3; 95% CI, 1.3 to 4.0), asthma requiring medication use in the previous 12 mo (OR, 2.1; 95% CI, 1.2 to 3.6), lifetime history of wheezing (OR, 1.8; 95% CI, 1.2 to 2.6), current wheezing with colds (OR, 2.1; 95% CI, 1.3 to 3.4) and without colds (OR, 2.5; 95% CI, 1.4 to 4.4), persistent wheezing (OR, 3.1; 95% CI, 1.6 to 6.1), wheezing with exercise (OR, 2.4 95% CI; 1.3 to 4.3), attacks of wheezing causing shortness of breath (OR, 2.4; 95% CI, 1.3 to 4.4) or awakening at night in the previous 12 mo (OR, 3.2; 95% CI, 1.7 to 5.8), and wheezing requiring medication (OR 2.1; 95% CI, 1.2 to 3.7) or emergency room visits during the previous year (OR, 3.4; 95% CI, 1.4 to 7.8). In contrast, current and previous ETS exposure was not associated with asthma prevalence, but was consistently associated with subcategories of wheezing. Current ETS exposure was associated with lifetime wheezing (OR, 1.3; 95% CI, 1.1 to 1.5), current wheezing with colds (OR, 1.6; 95% CI, 1.3 to 2.0) and without colds (OR, 1.5; 95% CI, 1.1 to 1.9), wheezing with exercise (OR, 1.7; 95% CI, 1.3 to 2.2), attacks of wheezing causing shortness of breath (OR, 1.6; 95% CI, 1.2 to 2.1) or awakening at night (OR, 1.5; 95% CI, 1.1 to 2.0), and wheezing requiring medication (OR, 1.4; 95% CI, 1.1 to 1.8) or emergency room visits within the previous year (OR, 1.9; 95% CI, 1.2 to 3.0). The effects of current ETS exposure on subcategories of wheezing were most pronounced among children exposed to two or more smokers and remained significant after adjusting for maternal smoking during pregnancy. We conclude that maternal smoking during pregnancy increases the occurrence of physician-diagnosed asthma and wheezing during childhood. In contrast, current ETS exposure is associated with wheezing, but not physician-diagnosed asthma. Taken together, our findings support the hypothesis that ETS operates as a cofactor with other insults such as intercurrent infections as a trigger of wheezing attacks, rather than as a factor that induces asthma, whereas in utero exposure acts to increase physician-diagnosed asthma.. parental smoking| childhood asthma| lung-function| family history| risk-factors| prevalence| exposure| communities| trends| birth.	FEB-2001	parental smoking| childhood asthma| lung-function| family history| risk-factors| prevalence| exposure| communities| trends| birth	Gilliland, FD; Li, YF; Peters, JM	Effects of maternal smoking during pregnancy and environmental tobacco smoke on asthma and wheezing in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		PARENTAL SMOKING; CHILDHOOD ASTHMA; LUNG-FUNCTION; FAMILY HISTORY; RISK-FACTORS; PREVALENCE; EXPOSURE; COMMUNITIES; TRENDS; BIRTH	The effects of maternal smoking during pregnancy and childhood environmental tobacco smoke (ETS) exposure on asthma and wheezing were investigated in 5,762 school-aged children residing in 12 Southern California communities. Responses to a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students were used to ascertain children with wheezing or physician-diagnosed asthma. Lifetime household exposures to tobacco smoke were assessed using responses about past and current smoking histories of household members and any history of maternal smoking during pregnancy. Logistic regression models were fitted to cross-sectional data to estimate the effects of in utero exposure to maternal smoking and previous and current ETS exposure on the prevalence of wheezing and physician-diagnosed asthma. In utero exposure to maternal smoking without subsequent postnatal ETS exposure was associated with increased prevalence of physician-diagnosed asthma (OR, 1.8; 95% CI, 1.1 to 2.9), asthma with current symptoms (OR, 2.3; 95% CI, 1.3 to 4.0), asthma requiring medication use in the previous 12 mo (OR, 2.1; 95% CI, 1.2 to 3.6), lifetime history of wheezing (OR, 1.8; 95% CI, 1.2 to 2.6), current wheezing with colds (OR, 2.1; 95% CI, 1.3 to 3.4) and without colds (OR, 2.5; 95% CI, 1.4 to 4.4), persistent wheezing (OR, 3.1; 95% CI, 1.6 to 6.1), wheezing with exercise (OR, 2.4 95% CI; 1.3 to 4.3), attacks of wheezing causing shortness of breath (OR, 2.4; 95% CI, 1.3 to 4.4) or awakening at night in the previous 12 mo (OR, 3.2; 95% CI, 1.7 to 5.8), and wheezing requiring medication (OR 2.1; 95% CI, 1.2 to 3.7) or emergency room visits during the previous year (OR, 3.4; 95% CI, 1.4 to 7.8). In contrast, current and previous ETS exposure was not associated with asthma prevalence, but was consistently associated with subcategories of wheezing. Current ETS exposure was associated with lifetime wheezing (OR, 1.3; 95% CI, 1.1 to 1.5), current wheezing with colds (OR, 1.6; 95% CI, 1.3 to 2.0) and without colds (OR, 1.5; 95% CI, 1.1 to 1.9), wheezing with exercise (OR, 1.7; 95% CI, 1.3 to 2.2), attacks of wheezing causing shortness of breath (OR, 1.6; 95% CI, 1.2 to 2.1) or awakening at night (OR, 1.5; 95% CI, 1.1 to 2.0), and wheezing requiring medication (OR, 1.4; 95% CI, 1.1 to 1.8) or emergency room visits within the previous year (OR, 1.9; 95% CI, 1.2 to 3.0). The effects of current ETS exposure on subcategories of wheezing were most pronounced among children exposed to two or more smokers and remained significant after adjusting for maternal smoking during pregnancy. We conclude that maternal smoking during pregnancy increases the occurrence of physician-diagnosed asthma and wheezing during childhood. In contrast, current ETS exposure is associated with wheezing, but not physician-diagnosed asthma. Taken together, our findings support the hypothesis that ETS operates as a cofactor with other insults such as intercurrent infections as a trigger of wheezing attacks, rather than as a factor that induces asthma, whereas in utero exposure acts to increase physician-diagnosed asthma.	35	296	2001	8		General & Internal Medicine; Respiratory System
Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report. Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative**, which is endorsed by both academies.. diagnosis| education| guidelines| monitoring| pediatric asthma| treatment|exhaled-nitric-oxide| exercise-induced asthma| short-term growth| randomized controlled-trial| house-dust mite| inhaled fluticasone propionate| respiratory-syncytial-virus| grass-pollen immunotherapy| metered-dose inhaler| skin-test reactivity.	JAN-2008	diagnosis| education| guidelines| monitoring| pediatric asthma| treatment|exhaled-nitric-oxide| exercise-induced asthma| short-term growth| randomized controlled-trial| house-dust mite| inhaled fluticasone propionate| respiratory-syncytial-virus| grass-pollen immunotherapy| metered-dose inhaler| skin-test reactivity	Bacharier, LB; Boner, A; Carlsen, KH; Eigenmann, PA; Frischer, T; Goetz, M; Helms, PJ; Hunt, J; Liu, A; Papadopoulos, N; Platts-Mills, T; Pohunek, P; Simons, FER; Valovirta, E; Wahn, U; Wildhaber, J	Diagnosis and treatment of asthma in childhood: a PRACTALL consensus report		ALLERGY	diagnosis; education; guidelines; monitoring; pediatric asthma; treatment	EXHALED-NITRIC-OXIDE; EXERCISE-INDUCED ASTHMA; SHORT-TERM GROWTH; RANDOMIZED CONTROLLED-TRIAL; HOUSE-DUST MITE; INHALED FLUTICASONE PROPIONATE; RESPIRATORY-SYNCYTIAL-VIRUS; GRASS-POLLEN IMMUNOTHERAPY; METERED-DOSE INHALER; SKIN-TEST REACTIVITY	Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative**, which is endorsed by both academies.	292	295	2008	30	10.1111/j.1398-9995.2007.01586.x	Allergy; Immunology
Estimating long-term average particulate air pollution concentrations: Application of traffic indicators and geographic information systems. Background. As part of a multicenter study relating traffic-related air pollution with incidence of asthma in three birth cohort studies (TRAPCA), we used a measurement and modelling procedure to estimate long-term average exposure to traffic-related particulate air pollution in communities throughout the Netherlands; in Munich, Germany; and in Stockholm County, Sweden. Methods. In each of the three locations, 40-42 measurement sites were selected to represent rural, urban background and urban traffic locations. At each site and fine particles and filter absorbance (a marker for diesel exhaust particles) were measured for four 2-week periods distributed over approximately 1-year periods between February 1999 and July 2000. We used these measurements to calculate annual average concentrations after adjustment for temporal variation. Traffic-related variables (eg, population density and traffic intensity) were collected using Geographic Information Systems and used in regression models predicting annual average concentrations. From these models we estimated ambient air concentrations at the home addresses of the cohort members. Results. Regression models using traffic-related variables explained 73%, 56% and 50% of the variability in annual average fine particle concentrations for the Netherlands, Munich arid Stockholm County, respectively. For filter absorbance, the regression models explained 81%, 67% and 66% of the variability in the annual average concentrations. Cross-validation to estimate the model prediction errors indicated root mean squared errors of 1.1-1.6 mug/m(3) for PM2.5 and 0.22-0.31 *10(-5)m(-1) for absorbance. Conclusions. A substantial fraction of the variability in annual average concentrations for all locations was explained by traffic-related variables. This approach can be used to estimate individual exposures for epidemiologic studies and offers advantages over alternative techniques relying on surrogate variables or traditional approaches that utilize ambient monitoring data alone.. air pollution| environmental epidemiology| particles| geographic information systems| gis| vehicle emissions|chronic respiratory symptoms| nitrogen-dioxide| hospital admissions| spatial variability| children| exposure| health| asthma| density| outdoor.	MAR-2003	air pollution| environmental epidemiology| particles| geographic information systems| gis| vehicle emissions|chronic respiratory symptoms| nitrogen-dioxide| hospital admissions| spatial variability| children| exposure| health| asthma| density| outdoor	Brauer, M; Hoek, G; van Vliet, P; Meliefste, K; Fischer, P; Gehring, U; Heinrich, J; Cyrys, J; Bellander, T; Lewne, M; Brunekreef, B	Estimating long-term average particulate air pollution concentrations: Application of traffic indicators and geographic information systems		EPIDEMIOLOGY	air pollution; environmental epidemiology; particles; geographic information systems; GIS; vehicle emissions	CHRONIC RESPIRATORY SYMPTOMS; NITROGEN-DIOXIDE; HOSPITAL ADMISSIONS; SPATIAL VARIABILITY; CHILDREN; EXPOSURE; HEALTH; ASTHMA; DENSITY; OUTDOOR	Background. As part of a multicenter study relating traffic-related air pollution with incidence of asthma in three birth cohort studies (TRAPCA), we used a measurement and modelling procedure to estimate long-term average exposure to traffic-related particulate air pollution in communities throughout the Netherlands; in Munich, Germany; and in Stockholm County, Sweden. Methods. In each of the three locations, 40-42 measurement sites were selected to represent rural, urban background and urban traffic locations. At each site and fine particles and filter absorbance (a marker for diesel exhaust particles) were measured for four 2-week periods distributed over approximately 1-year periods between February 1999 and July 2000. We used these measurements to calculate annual average concentrations after adjustment for temporal variation. Traffic-related variables (eg, population density and traffic intensity) were collected using Geographic Information Systems and used in regression models predicting annual average concentrations. From these models we estimated ambient air concentrations at the home addresses of the cohort members. Results. Regression models using traffic-related variables explained 73%, 56% and 50% of the variability in annual average fine particle concentrations for the Netherlands, Munich arid Stockholm County, respectively. For filter absorbance, the regression models explained 81%, 67% and 66% of the variability in the annual average concentrations. Cross-validation to estimate the model prediction errors indicated root mean squared errors of 1.1-1.6 mug/m(3) for PM2.5 and 0.22-0.31 *10(-5)m(-1) for absorbance. Conclusions. A substantial fraction of the variability in annual average concentrations for all locations was explained by traffic-related variables. This approach can be used to estimate individual exposures for epidemiologic studies and offers advantages over alternative techniques relying on surrogate variables or traditional approaches that utilize ambient monitoring data alone.	39	295	2003	12	10.1097/00001648-200303000-00019	Public, Environmental & Occupational Health
Impact of changes in transportation and commuting behaviors during the 1996 Summer Olympic Games in Atlanta on air quality and childhood asthma. Context Vehicle exhaust is a major source of ozone and other air pollutants. Although high ground-level ozone pollution is associated with transient increases in asthma morbidity, the impact of citywide transportation changes on air quality and childhood asthma has not been studied. The alternative transportation strategy implemented during the 1996 Summer Olympic Games in Atlanta, Ga, provided such an opportunity. Objective To describe traffic changes in Atlanta, Ca, during the 1996 Summer Olympic Games and concomitant changes in air quality and childhood asthma events. Design Ecological study comparing the 17 days of the Olympic Games (July 19-August 4, 1996) to a baseline period consisting of the 4 weeks before and 4 weeks after the Olympic Games. Setting and Subjects Children aged 1 to 16 years who resided in the 5 central counties of metropolitan Atlanta and whose data were captured in 1 of 4 databases. Main Outcome Measures Citywide acute care visits and hospitalizations for asthma (asthma events) and nonasthma events, concentrations of major air pollutants, meteorological variables, and traffic counts. Results During the Olympic Games, the number of asthma acute care events decreased 41.6% (4.23 vs 2.47 daily events) in the Georgia Medicaid claims file, 44.1% (1.36 vs 0.76 daily events) in a health maintenance organization database, 11.1% (4.77 vs 4.24 daily events) in 2 pediatric emergency departments, and 19.1% (2.04 vs 1.65 daily hospitalizations) in the Georgia Hospital Discharge Database. The number of nonasthma acute care events in the 4 databases changed -3.1%, +1.3%, -2.1%, and +1.0%, respectively. In multivariate regression analysis, only the reduction in asthma events recorded in the Medicaid database was significant (relative risk, 0.48; 95% confidence interval, 0.44-0.86). Peak daily ozone concentrations decreased 27.9%, from 81.3 ppb during the baseline period to 58.6 ppb during the Olympic Games (P<.001). Peak weekday morning traffic counts dropped 22.5% (P<.001). Traffic counts were significantly correlated with that day's peak ozone concentration (average r=0.36 for all 4 roads examined). Meteorological conditions during the Olympic Games did not differ substantially from the baseline period. Conclusions Efforts to reduce downtown traffic congestion in Atlanta during the Olympic Games resulted in decreased traffic density, especially during the critical morning period. This was associated with a prolonged reduction in ozone pollution and significantly lower rates of childhood asthma events. These data provide support for efforts to reduce air pollution and improve health via reductions in motor vehicle traffic.. environmental-factors| hospital admissions| respiratory health| united-kingdom| mexico-city| pollution| children| ozone| prevalence| mortality.	FEB 21-2001	environmental-factors| hospital admissions| respiratory health| united-kingdom| mexico-city| pollution| children| ozone| prevalence| mortality	Friedman, MS; Powell, KE; Hutwagner, L; Graham, LM; Teague, WG	Impact of changes in transportation and commuting behaviors during the 1996 Summer Olympic Games in Atlanta on air quality and childhood asthma		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		ENVIRONMENTAL-FACTORS; HOSPITAL ADMISSIONS; RESPIRATORY HEALTH; UNITED-KINGDOM; MEXICO-CITY; POLLUTION; CHILDREN; OZONE; PREVALENCE; MORTALITY	Context Vehicle exhaust is a major source of ozone and other air pollutants. Although high ground-level ozone pollution is associated with transient increases in asthma morbidity, the impact of citywide transportation changes on air quality and childhood asthma has not been studied. The alternative transportation strategy implemented during the 1996 Summer Olympic Games in Atlanta, Ga, provided such an opportunity. Objective To describe traffic changes in Atlanta, Ca, during the 1996 Summer Olympic Games and concomitant changes in air quality and childhood asthma events. Design Ecological study comparing the 17 days of the Olympic Games (July 19-August 4, 1996) to a baseline period consisting of the 4 weeks before and 4 weeks after the Olympic Games. Setting and Subjects Children aged 1 to 16 years who resided in the 5 central counties of metropolitan Atlanta and whose data were captured in 1 of 4 databases. Main Outcome Measures Citywide acute care visits and hospitalizations for asthma (asthma events) and nonasthma events, concentrations of major air pollutants, meteorological variables, and traffic counts. Results During the Olympic Games, the number of asthma acute care events decreased 41.6% (4.23 vs 2.47 daily events) in the Georgia Medicaid claims file, 44.1% (1.36 vs 0.76 daily events) in a health maintenance organization database, 11.1% (4.77 vs 4.24 daily events) in 2 pediatric emergency departments, and 19.1% (2.04 vs 1.65 daily hospitalizations) in the Georgia Hospital Discharge Database. The number of nonasthma acute care events in the 4 databases changed -3.1%, +1.3%, -2.1%, and +1.0%, respectively. In multivariate regression analysis, only the reduction in asthma events recorded in the Medicaid database was significant (relative risk, 0.48; 95% confidence interval, 0.44-0.86). Peak daily ozone concentrations decreased 27.9%, from 81.3 ppb during the baseline period to 58.6 ppb during the Olympic Games (P<.001). Peak weekday morning traffic counts dropped 22.5% (P<.001). Traffic counts were significantly correlated with that day's peak ozone concentration (average r=0.36 for all 4 roads examined). Meteorological conditions during the Olympic Games did not differ substantially from the baseline period. Conclusions Efforts to reduce downtown traffic congestion in Atlanta during the Olympic Games resulted in decreased traffic density, especially during the critical morning period. This was associated with a prolonged reduction in ozone pollution and significantly lower rates of childhood asthma events. These data provide support for efforts to reduce air pollution and improve health via reductions in motor vehicle traffic.	45	290	2001	9	10.1001/jama.285.7.897	General & Internal Medicine
Extrathymically generated regulatory T cells control mucosal T(H)2 inflammation. A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, which are sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma and intestinal inflammation(1). Regulatory T (T-reg) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tT(reg) cells) and in the periphery (induced (i)T-reg cells), and their dual origin implies a division of labour between tT(reg) and iT(reg) cells in immune homeostasis. Here we show that a highly selective blockage in differentiation of iT(reg) cells in mice did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology, or increased pro-inflammatory responses of T helper 1 (T(H)1) and T(H)17 cells. However, mice deficient in iT(reg) cells spontaneously developed pronounced T(H)2-type pathologies at mucosal sites-in the gastrointestinal tract and lungs-with hallmarks of allergic inflammation and asthma. Furthermore, iT(reg)-cell deficiency altered gut microbial communities. These results suggest that whereas T-reg cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of T-reg cells affects commensal microbiota composition and serves a distinct, essential function in restraint of allergic-type inflammation at mucosal interfaces.. transcription factor foxp3| in-vivo| bowel-disease| induction| responses| lineage| fate| gene| mice| homeostasis.	FEB 16-2012	transcription factor foxp3| in-vivo| bowel-disease| induction| responses| lineage| fate| gene| mice| homeostasis	Josefowicz, SZ; Niec, RE; Kim, HY; Treuting, P; Chinen, T; Zheng, Y; Umetsu, DT; Rudensky, AY	Extrathymically generated regulatory T cells control mucosal T(H)2 inflammation		NATURE		TRANSCRIPTION FACTOR FOXP3; IN-VIVO; BOWEL-DISEASE; INDUCTION; RESPONSES; LINEAGE; FATE; GENE; MICE; HOMEOSTASIS	A balance between pro- and anti-inflammatory mechanisms at mucosal interfaces, which are sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma and intestinal inflammation(1). Regulatory T (T-reg) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tT(reg) cells) and in the periphery (induced (i)T-reg cells), and their dual origin implies a division of labour between tT(reg) and iT(reg) cells in immune homeostasis. Here we show that a highly selective blockage in differentiation of iT(reg) cells in mice did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology, or increased pro-inflammatory responses of T helper 1 (T(H)1) and T(H)17 cells. However, mice deficient in iT(reg) cells spontaneously developed pronounced T(H)2-type pathologies at mucosal sites-in the gastrointestinal tract and lungs-with hallmarks of allergic inflammation and asthma. Furthermore, iT(reg)-cell deficiency altered gut microbial communities. These results suggest that whereas T-reg cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of T-reg cells affects commensal microbiota composition and serves a distinct, essential function in restraint of allergic-type inflammation at mucosal interfaces.	39	288	2012	6	10.1038/nature10772	Science & Technology - Other Topics
Prenatal Tobacco Smoke Exposure Affects Global and Gene-specific DNA Methylation. Rationale: Prenatal exposure to tobacco smoke increases the risk for diseases later in the child's life that may be mediated through alterations in DNA methylation. Objectives: To demonstrate that differences in DNA methylation patterns occur in children exposed to tobacco smoke and that variation in detoxification genes may alter these associations. Methods: Methylation of DNA repetitive elements, LINE1 and AluYb8, was measured using bisulfite conversion and pyrosequencing in buccal cells of 348 children participating in the Children's Health Study. Gene-specific CpG methylation differences associated with smoke exposure were screened in 272 participants in the Children's Health Study children using an Illumina GoldenGate panel. CpG loci that demonstrated a statistically significant difference in methylation were validated by pyrosequencing. Estimates were standardized across loci using a Z score to enable cross-comparison of results. Measurements and Main Results: DNA methylation patterns were associated with in utero exposure to maternal smoking. Exposed children had significantly lower methylation of AluYb8 (beta, -0.31; P = 0.03). Differences in smoking-related effects on LINE1 methylation were observed in children with the common GSTM1 null genotype. Differential methylation of CpG loci in eight genes was identified through the screen. Two genes, AXL and PTPRO, were validated by pyrosequencing and showed significant increases in methylation of 0.37 (P = 0.005) and 0.34 (P = 0.02) in exposed children. The associations with maternal smoking varied by a common GSTP1 haplotype. Conclusions: Life-long effects of in utero exposures may be mediated through alterations in DNA methylation. Variants in detoxification genes may modulate the effects of in utero exposure through epigenetic mechanisms.. dna methylation| epigenetics| prenatal| smoke|childhood asthma| tyrosine phosphatases| epigenetic regulation| maternal smoking| cigarette-smoke| passive smoking| expression| children| susceptibility.	SEP 1-2009	dna methylation| epigenetics| prenatal| smoke|childhood asthma| tyrosine phosphatases| epigenetic regulation| maternal smoking| cigarette-smoke| passive smoking| expression| children| susceptibility	Breton, CV; Byun, HM; Wenten, M; Pan, F; Yang, A; Gilliland, FD	Prenatal Tobacco Smoke Exposure Affects Global and Gene-specific DNA Methylation		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	DNA methylation; epigenetics; prenatal; smoke	CHILDHOOD ASTHMA; TYROSINE PHOSPHATASES; EPIGENETIC REGULATION; MATERNAL SMOKING; CIGARETTE-SMOKE; PASSIVE SMOKING; EXPRESSION; CHILDREN; SUSCEPTIBILITY	Rationale: Prenatal exposure to tobacco smoke increases the risk for diseases later in the child's life that may be mediated through alterations in DNA methylation. Objectives: To demonstrate that differences in DNA methylation patterns occur in children exposed to tobacco smoke and that variation in detoxification genes may alter these associations. Methods: Methylation of DNA repetitive elements, LINE1 and AluYb8, was measured using bisulfite conversion and pyrosequencing in buccal cells of 348 children participating in the Children's Health Study. Gene-specific CpG methylation differences associated with smoke exposure were screened in 272 participants in the Children's Health Study children using an Illumina GoldenGate panel. CpG loci that demonstrated a statistically significant difference in methylation were validated by pyrosequencing. Estimates were standardized across loci using a Z score to enable cross-comparison of results. Measurements and Main Results: DNA methylation patterns were associated with in utero exposure to maternal smoking. Exposed children had significantly lower methylation of AluYb8 (beta, -0.31; P = 0.03). Differences in smoking-related effects on LINE1 methylation were observed in children with the common GSTM1 null genotype. Differential methylation of CpG loci in eight genes was identified through the screen. Two genes, AXL and PTPRO, were validated by pyrosequencing and showed significant increases in methylation of 0.37 (P = 0.005) and 0.34 (P = 0.02) in exposed children. The associations with maternal smoking varied by a common GSTP1 haplotype. Conclusions: Life-long effects of in utero exposures may be mediated through alterations in DNA methylation. Variants in detoxification genes may modulate the effects of in utero exposure through epigenetic mechanisms.	32	286	2009	6	10.1164/rccm.200901-0135OC	General & Internal Medicine; Respiratory System
The Generation R Study: design and cohort update 2012. The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on six areas of research: (1) maternal health; (2) growth and physical development; (3) behavioural and cognitive development; (4) respiratory health and allergies; (5) diseases in childhood; and (6) health and healthcare for children and their parents. Main exposures of interest include environmental, endocrine, genetic and epigenetic, lifestyle related, nutritional and socio-demographic determinants. In total, n = 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Response at baseline was 61 %, and general follow-up rates until the age of 6 years exceed 80 %. Data collection in mothers, fathers and children include questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome and epigenome wide association screen is available in the participating children. From the age of 5 years, regular detailed hands-on assessments are performed in a dedicated research center including advanced imaging facilities such as Magnetic Resonance Imaging. Eventually, results forthcoming from the Generation R Study contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.. cohort| pregnancy| child| fetal|population-based cohort| quality-of-life| child health questionnaire| genome-wide association| ischemic-heart-disease| all-cause mortality| fetal-growth| behavior questionnaire| physical-activity| common variants.	SEP-2012	cohort| pregnancy| child| fetal|population-based cohort| quality-of-life| child health questionnaire| genome-wide association| ischemic-heart-disease| all-cause mortality| fetal-growth| behavior questionnaire| physical-activity| common variants	Jaddoe, VWV; van Duijn, CM; Franco, OH; van der Heijden, AJ; van Ijzendoorn, MH; de Jongste, JC; van der Lugt, A; Mackenbach, JP; Moll, HA; Raat, H; Rivadeneira, F; Steegers, EAP; Tiemeier, H; Uitterlinden, AG; Verhulst, FC; Hofman, A	The Generation R Study: design and cohort update 2012		EUROPEAN JOURNAL OF EPIDEMIOLOGY	Cohort; Pregnancy; Child; Fetal	POPULATION-BASED COHORT; QUALITY-OF-LIFE; CHILD HEALTH QUESTIONNAIRE; GENOME-WIDE ASSOCIATION; ISCHEMIC-HEART-DISEASE; ALL-CAUSE MORTALITY; FETAL-GROWTH; BEHAVIOR QUESTIONNAIRE; PHYSICAL-ACTIVITY; COMMON VARIANTS	The Generation R Study is a population-based prospective cohort study from fetal life until adulthood. The study is designed to identify early environmental and genetic causes and causal pathways leading to normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on six areas of research: (1) maternal health; (2) growth and physical development; (3) behavioural and cognitive development; (4) respiratory health and allergies; (5) diseases in childhood; and (6) health and healthcare for children and their parents. Main exposures of interest include environmental, endocrine, genetic and epigenetic, lifestyle related, nutritional and socio-demographic determinants. In total, n = 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. Response at baseline was 61 %, and general follow-up rates until the age of 6 years exceed 80 %. Data collection in mothers, fathers and children include questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome and epigenome wide association screen is available in the participating children. From the age of 5 years, regular detailed hands-on assessments are performed in a dedicated research center including advanced imaging facilities such as Magnetic Resonance Imaging. Eventually, results forthcoming from the Generation R Study contribute to the development of strategies for optimizing health and healthcare for pregnant women and children.	202	285	2012	18	10.1007/s10654-012-9735-1	Public, Environmental & Occupational Health
Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. Type I allergy is an immunoglobulin E (IgE)-mediated hypersensitivity disease affecting more than 25% of the population. Currently, diagnosis of allergy is performed by provocation testing and IgE serology using allergen extracts. This process defines allergen-containing sources but cannot identify the disease-eliciting allergenic molecules. We have applied microarray technology to develop a miniaturized allergy test containing 94 purified allergen molecules that represent the most common allergen sources. The allergen microarray allows the determination and monitoring of allergic patients' IgE reactivity profiles to large numbers of disease-causing allergens by using single measurements and minute amounts of serum. This method may change established practice in allergy diagnosis, prevention, and therapy. In addition, microarrayed antigens may be applied to the diagnosis of autoimmune and infectious diseases.. type i allergy| ige| microarray technology| recombinant allergen| diagnosis|grass phleum-pratense| house-dust mite| birch pollen allergen| ige-binding epitopes| amino-acid-sequence| aspergillus-fumigatus allergens| penicillium-citrinum allergen| cockroach blattella-germanica| surface display technology| antigenic cross-reactivity.	JAN-2002	type i allergy| ige| microarray technology| recombinant allergen| diagnosis|grass phleum-pratense| house-dust mite| birch pollen allergen| ige-binding epitopes| amino-acid-sequence| aspergillus-fumigatus allergens| penicillium-citrinum allergen| cockroach blattella-germanica| surface display technology| antigenic cross-reactivity	Hiller, R; Laffer, S; Harwanegg, C; Huber, M; Schmidt, WM; Twardosz, A; Barletta, B; Becker, WM; Blaser, K; Breiteneder, H; Chapman, M; Crameri, R; Duchene, M; Ferreira, F; Fiebig, H; Hoffmann-Sommergruber, K; King, TP; Kleber-Janke, T; Kurup, VP; Lehrer, SB; Lidholm, J; Muller, U; Pini, C; Reese, G; Scheiner, O; Scheynius, A; Shen, HD; Spitzauer, S; Suck, R; Swoboda, I; Thomas, W; Tinghino, R; Van Hage-Hamsten, M; Virtanen, T; Kraft, D; Muller, MW; Valenta, R	Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment		FASEB JOURNAL	type I allergy; IgE; microarray technology; recombinant allergen; diagnosis	GRASS PHLEUM-PRATENSE; HOUSE-DUST MITE; BIRCH POLLEN ALLERGEN; IGE-BINDING EPITOPES; AMINO-ACID-SEQUENCE; ASPERGILLUS-FUMIGATUS ALLERGENS; PENICILLIUM-CITRINUM ALLERGEN; COCKROACH BLATTELLA-GERMANICA; SURFACE DISPLAY TECHNOLOGY; ANTIGENIC CROSS-REACTIVITY	Type I allergy is an immunoglobulin E (IgE)-mediated hypersensitivity disease affecting more than 25% of the population. Currently, diagnosis of allergy is performed by provocation testing and IgE serology using allergen extracts. This process defines allergen-containing sources but cannot identify the disease-eliciting allergenic molecules. We have applied microarray technology to develop a miniaturized allergy test containing 94 purified allergen molecules that represent the most common allergen sources. The allergen microarray allows the determination and monitoring of allergic patients' IgE reactivity profiles to large numbers of disease-causing allergens by using single measurements and minute amounts of serum. This method may change established practice in allergy diagnosis, prevention, and therapy. In addition, microarrayed antigens may be applied to the diagnosis of autoimmune and infectious diseases.	90	285	2002	21	10.1096/fj.01-0711fje	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology
Health effects of air pollution. The general public, especially patients with upper or lower respiratory symptoms, is aware from media reports that adverse respiratory effects can occur from air pollution. It is important for the allergist to have a current knowledge of the potential health effects of air pollution and how they might affect their patients to advise them accordingly. Specifically, the allergist-clinical immunologist should be keenly aware that both gaseous and particulate outdoor pollutants might aggravate or enhance the underlying pathophysiology of both the upper and lower airways. Epidemiologic and laboratory exposure research studies investigating the health effects of outdoor air pollution each have advantages and disadvantages. Epidemiologic studies can show statistical associations between levels of individual or combined air pollutants and outcomes, such as rates of asthma, emergency visits for asthma, or hospital admissions, but cannot prove a causative role. Human exposure studies, animal models, and tissue or cellular studies provide further information on mechanisms of response but also have inherent limitations. The aim of this rostrum is to review the relevant publications that provide the appropriate context for assessing the risks of air pollution relative to other more modifiable environmental factors in patients with allergic airways disease.. outdoor air pollution| particulate matter| ozone| nitrogen dioxide| sulfur dioxide| diesel exhaust| asthma| exposure| interactions between allergens and pollutants|diesel exhaust particles| nitrogen-dioxide exposure| daily asthma severity| mild allergic-asthma| 20 us cities| ozone exposure| inhaled allergen| sulfur-dioxide| fungal spores| inflammatory responses.	NOV-2004	outdoor air pollution| particulate matter| ozone| nitrogen dioxide| sulfur dioxide| diesel exhaust| asthma| exposure| interactions between allergens and pollutants|diesel exhaust particles| nitrogen-dioxide exposure| daily asthma severity| mild allergic-asthma| 20 us cities| ozone exposure| inhaled allergen| sulfur-dioxide| fungal spores| inflammatory responses	Bernstein, JA; Alexis, N; Barnes, C; Bernstein, IL; Bernstein, JA; Nel, A; Peden, D; Diaz-Sanchez, D; Tarlo, SM; Williams, PB	Health effects of air pollution		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	outdoor air pollution; particulate matter; ozone; nitrogen dioxide; sulfur dioxide; diesel exhaust; asthma; exposure; interactions between allergens and pollutants	DIESEL EXHAUST PARTICLES; NITROGEN-DIOXIDE EXPOSURE; DAILY ASTHMA SEVERITY; MILD ALLERGIC-ASTHMA; 20 US CITIES; OZONE EXPOSURE; INHALED ALLERGEN; SULFUR-DIOXIDE; FUNGAL SPORES; INFLAMMATORY RESPONSES	The general public, especially patients with upper or lower respiratory symptoms, is aware from media reports that adverse respiratory effects can occur from air pollution. It is important for the allergist to have a current knowledge of the potential health effects of air pollution and how they might affect their patients to advise them accordingly. Specifically, the allergist-clinical immunologist should be keenly aware that both gaseous and particulate outdoor pollutants might aggravate or enhance the underlying pathophysiology of both the upper and lower airways. Epidemiologic and laboratory exposure research studies investigating the health effects of outdoor air pollution each have advantages and disadvantages. Epidemiologic studies can show statistical associations between levels of individual or combined air pollutants and outcomes, such as rates of asthma, emergency visits for asthma, or hospital admissions, but cannot prove a causative role. Human exposure studies, animal models, and tissue or cellular studies provide further information on mechanisms of response but also have inherent limitations. The aim of this rostrum is to review the relevant publications that provide the appropriate context for assessing the risks of air pollution relative to other more modifiable environmental factors in patients with allergic airways disease.	82	283	2004	8	10.1016/j.jaci.2004.08.030	Allergy; Immunology
Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City Children. BACKGROUND Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control. METHODS We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for 60 weeks, and the primary outcome was symptoms of asthma. RESULTS Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.48 days per 2-week interval, a 24.5% decrease (P<0.001). Similarly, omalizumab significantly reduced the proportion of participants who had one or more exacerbations from 48.8 to 30.3% (P<0.001). Improvements occurred with omalizumab despite reductions in the use of inhaled glucocorticoids and long-acting beta-agonists. CONCLUSIONS When added to a regimen of guidelines-based therapy for inner-city children, adolescents, and young adults, omalizumab further improved asthma control, nearly eliminated seasonal peaks in exacerbations, and reduced the need for other medications to control asthma.. severe allergic-asthma| monoclonal-antibody| cost-effectiveness| childhood asthma| exacerbations| viruses| adults| cells| adolescents| rhinovirus.	MAR 17-2011	severe allergic-asthma| monoclonal-antibody| cost-effectiveness| childhood asthma| exacerbations| viruses| adults| cells| adolescents| rhinovirus	Busse, WW; Morgan, WJ; Gergen, PJ; Mitchell, HE; Gern, JE; Liu, AH; Gruchalla, RS; Kattan, M; Teach, SJ; Pongracic, JA; Chmiel, JF; Steinbach, SF; Calatroni, A; Togias, A; Thompson, KM; Szefler, SJ; Sorkness, CA	Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City Children		NEW ENGLAND JOURNAL OF MEDICINE		SEVERE ALLERGIC-ASTHMA; MONOCLONAL-ANTIBODY; COST-EFFECTIVENESS; CHILDHOOD ASTHMA; EXACERBATIONS; VIRUSES; ADULTS; CELLS; ADOLESCENTS; RHINOVIRUS	BACKGROUND Research has underscored the effects of exposure and sensitization to allergens on the severity of asthma in inner-city children. It has also revealed the limitations of environmental remediation and guidelines-based therapy in achieving greater disease control. METHODS We enrolled inner-city children, adolescents, and young adults with persistent asthma in a randomized, double-blind, placebo-controlled, parallel-group trial at multiple centers to assess the effectiveness of omalizumab, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for 60 weeks, and the primary outcome was symptoms of asthma. RESULTS Among 419 participants who underwent randomization (at which point 73% had moderate or severe disease), omalizumab as compared with placebo significantly reduced the number of days with asthma symptoms, from 1.96 to 1.48 days per 2-week interval, a 24.5% decrease (P<0.001). Similarly, omalizumab significantly reduced the proportion of participants who had one or more exacerbations from 48.8 to 30.3% (P<0.001). Improvements occurred with omalizumab despite reductions in the use of inhaled glucocorticoids and long-acting beta-agonists. CONCLUSIONS When added to a regimen of guidelines-based therapy for inner-city children, adolescents, and young adults, omalizumab further improved asthma control, nearly eliminated seasonal peaks in exacerbations, and reduced the need for other medications to control asthma.	42	281	2011	11		General & Internal Medicine
Gender differences in the disposition and toxicity of metals. There is increasing evidence that health effects of toxic metals differ in prevalence or are manifested differently in men and women. However, the database is small. The present work aims at evaluating gender differences in the health effects of cadmium, nickel, lead, mercury and arsenic. There is a markedly higher prevalence of nickel-induced allergy and hand eczema in women compared to men, mainly due to differences in exposure. Cadmium retention is generally higher in women than in men, and the severe cadmium-induced Itai-itai disease was mainly a woman's disease. Gender differences in susceptibility at lower exposure are uncertain, but recent data indicate that cadmium has estrogenic effects and affect female offspring. Men generally have higher blood lead levels than women. Lead accumulates in bone and increased endogenous lead exposure has been demonstrated during periods of increased bone turnover, particularly in women in pregnancy and menopause. Lead and mercury, in the form of mercury vapor and methylmercury, are easily transferred from the pregnant women to the fetus. Recent data indicate that boys are more susceptible to neurotoxic effects of lead and methylmercury following exposure early in life, while experimental data suggest that females are more susceptible to immunotoxic effects of lead. Certain gender differences in the biotransformation of arsenic by methylation have been reported, and men seem to be more affected by arsenic-related skin effect than women. Experimental studies indicate major gender differences in arsenic-induced cancer. Obviously, research on gender-related differences in health effects caused by metals needs considerable more focus in the future. (c) 2006 Elsevier Inc. All rights reserved.. gender| females| males| exposure| toxicity| metabolism| susceptibility|breast-cancer cells| environmental cadmium exposure| estrogen-receptor-alpha| mercury-treated rats| forearm bone-density| water supply-system| low-level exposure| blood lead levels| drinking-water| methyl mercury.	MAY-2007	gender| females| males| exposure| toxicity| metabolism| susceptibility|breast-cancer cells| environmental cadmium exposure| estrogen-receptor-alpha| mercury-treated rats| forearm bone-density| water supply-system| low-level exposure| blood lead levels| drinking-water| methyl mercury	Vahter, M; Akesson, A; Liden, C; Ceccatelli, S; Berglund, M	Gender differences in the disposition and toxicity of metals		ENVIRONMENTAL RESEARCH	gender; females; males; exposure; toxicity; metabolism; susceptibility	BREAST-CANCER CELLS; ENVIRONMENTAL CADMIUM EXPOSURE; ESTROGEN-RECEPTOR-ALPHA; MERCURY-TREATED RATS; FOREARM BONE-DENSITY; WATER SUPPLY-SYSTEM; LOW-LEVEL EXPOSURE; BLOOD LEAD LEVELS; DRINKING-WATER; METHYL MERCURY	There is increasing evidence that health effects of toxic metals differ in prevalence or are manifested differently in men and women. However, the database is small. The present work aims at evaluating gender differences in the health effects of cadmium, nickel, lead, mercury and arsenic. There is a markedly higher prevalence of nickel-induced allergy and hand eczema in women compared to men, mainly due to differences in exposure. Cadmium retention is generally higher in women than in men, and the severe cadmium-induced Itai-itai disease was mainly a woman's disease. Gender differences in susceptibility at lower exposure are uncertain, but recent data indicate that cadmium has estrogenic effects and affect female offspring. Men generally have higher blood lead levels than women. Lead accumulates in bone and increased endogenous lead exposure has been demonstrated during periods of increased bone turnover, particularly in women in pregnancy and menopause. Lead and mercury, in the form of mercury vapor and methylmercury, are easily transferred from the pregnant women to the fetus. Recent data indicate that boys are more susceptible to neurotoxic effects of lead and methylmercury following exposure early in life, while experimental data suggest that females are more susceptible to immunotoxic effects of lead. Certain gender differences in the biotransformation of arsenic by methylation have been reported, and men seem to be more affected by arsenic-related skin effect than women. Experimental studies indicate major gender differences in arsenic-induced cancer. Obviously, research on gender-related differences in health effects caused by metals needs considerable more focus in the future. (c) 2006 Elsevier Inc. All rights reserved.	176	281	2007	11	10.1016/j.envres.2006.08.003	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Prevalence and independent risk factors for erectile dysfunction in Spain: Results of the Epidemiologia de la Disfuncion Erectil Masculina study. Purpose: We determined the prevalence of and risks factors for erectile dysfunction in Spain in a cross-sectional study. Materials and Methods: A total of 2,476 noninstitutionalized Spanish men 25 to 70 years old were interviewed at home and answered a self-administered questionnaire of 71 items, including 2 instruments to define erectile dysfunction, a simple self-assessment question to estimate erectile function and the International Index of Erectile Function. Data on disease, medication and toxic habits were also obtained. Results: With an overall participation rate of 75% the prevalence of erectile dysfunction according to the simple question was 12.1%. According to the erectile function domain of the International Index of Erectile Function the overall prevalence was 18.9%. Several independent risk factors were significantly associated with the probability of erectile dysfunction. Some differences arose according to the tool used to define the condition. However, there was a strong relationship of patient age with frequency or severity no matter which instrument was used to define erectile dysfunction. Diabetes (age adjusted odds ratio 4), high blood pressure (odds ratio 1.58), high cholesterol (1.63), peripheral vascular disorder (2.63), lung disease (3.11), prostate disease (2.93), cardiac problems (1.79), rheumatism (2.37) and allergy (3.08) were significantly associated with erectile dysfunction. Drug intake, which respondents called medication for nerves and sleeping pills, correlated strongly (odds ratio 2.78 and 4.27, respectively), as did tobacco use (2.5) and alcohol consumption (1.53). Conclusions: This study provides data on the prevalence of and risks factors for erectile dysfunction in Spain. The relationship of erectile dysfunction with certain risk factors, such as cardiovascular risk factors and drugs intake, are well known and our study corroborates these associations. Other associations with erectile dysfunction, such as prostate disease, allergy and rheumatism, support findings in previous reports, although to our knowledge the pathophysiological mechanisms remain unclear. Estimating the strength of the association of erectile dysfunction with distinct risk factors in terms of odds ratios enabled us to identify the factors to pursue when seeking to prevent erectile dysfunction. Furthermore, the relationship of tobacco with erectile dysfunction, which has been controversial in previous series, was well characterized in our study.. impotence| questionnaires| epidemiology| risk factors|male sexual dysfunction| international index| function domain| self-assessment| impotence| alcoholism| smoking.	AUG-2001	impotence| questionnaires| epidemiology| risk factors|male sexual dysfunction| international index| function domain| self-assessment| impotence| alcoholism| smoking	Martin-Morales, A; Sanchez-Cruz, JJ; de Tejada, IS; Rodriguez-Vela, L; Jimenez-Cruz, JF; Burgos-Rodriguez, R	Prevalence and independent risk factors for erectile dysfunction in Spain: Results of the Epidemiologia de la Disfuncion Erectil Masculina study		JOURNAL OF UROLOGY	impotence; questionnaires; epidemiology; risk factors	MALE SEXUAL DYSFUNCTION; INTERNATIONAL INDEX; FUNCTION DOMAIN; SELF-ASSESSMENT; IMPOTENCE; ALCOHOLISM; SMOKING	Purpose: We determined the prevalence of and risks factors for erectile dysfunction in Spain in a cross-sectional study. Materials and Methods: A total of 2,476 noninstitutionalized Spanish men 25 to 70 years old were interviewed at home and answered a self-administered questionnaire of 71 items, including 2 instruments to define erectile dysfunction, a simple self-assessment question to estimate erectile function and the International Index of Erectile Function. Data on disease, medication and toxic habits were also obtained. Results: With an overall participation rate of 75% the prevalence of erectile dysfunction according to the simple question was 12.1%. According to the erectile function domain of the International Index of Erectile Function the overall prevalence was 18.9%. Several independent risk factors were significantly associated with the probability of erectile dysfunction. Some differences arose according to the tool used to define the condition. However, there was a strong relationship of patient age with frequency or severity no matter which instrument was used to define erectile dysfunction. Diabetes (age adjusted odds ratio 4), high blood pressure (odds ratio 1.58), high cholesterol (1.63), peripheral vascular disorder (2.63), lung disease (3.11), prostate disease (2.93), cardiac problems (1.79), rheumatism (2.37) and allergy (3.08) were significantly associated with erectile dysfunction. Drug intake, which respondents called medication for nerves and sleeping pills, correlated strongly (odds ratio 2.78 and 4.27, respectively), as did tobacco use (2.5) and alcohol consumption (1.53). Conclusions: This study provides data on the prevalence of and risks factors for erectile dysfunction in Spain. The relationship of erectile dysfunction with certain risk factors, such as cardiovascular risk factors and drugs intake, are well known and our study corroborates these associations. Other associations with erectile dysfunction, such as prostate disease, allergy and rheumatism, support findings in previous reports, although to our knowledge the pathophysiological mechanisms remain unclear. Estimating the strength of the association of erectile dysfunction with distinct risk factors in terms of odds ratios enabled us to identify the factors to pursue when seeking to prevent erectile dysfunction. Furthermore, the relationship of tobacco with erectile dysfunction, which has been controversial in previous series, was well characterized in our study.	29	278	2001	6	10.1016/S0022-5347(05)65986-1	Urology & Nephrology
Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. Objective: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abello, Horsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. Methods: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. Results: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. Conclusion: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. Clinical implications: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use.. allergy| asthma| grass pollen| immunotherapy| sublingual| rhinoconjunctivitis| tablet-based| double-blind| placebo-controlled| phleum pratense|randomized controlled-trial| pollen immunotherapy| hay-fever| rhinitis| asthma| metaanalysis| children.	AUG-2006	allergy| asthma| grass pollen| immunotherapy| sublingual| rhinoconjunctivitis| tablet-based| double-blind| placebo-controlled| phleum pratense|randomized controlled-trial| pollen immunotherapy| hay-fever| rhinitis| asthma| metaanalysis| children	Dahl, R; Kapp, A; Colombo, G; deMonchy, JGR; Rak, S; Emminger, W; Rivas, MF; Ribel, M; Durham, SR	Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; asthma; grass pollen; immunotherapy; sublingual; rhinoconjunctivitis; tablet-based; double-blind; placebo-controlled; Phleum pratense	RANDOMIZED CONTROLLED-TRIAL; POLLEN IMMUNOTHERAPY; HAY-FEVER; RHINITIS; ASTHMA; METAANALYSIS; CHILDREN	Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. Objective: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abello, Horsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. Methods: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. Results: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. Conclusion: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. Clinical implications: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use.	21	277	2006	7	10.1016/j.jaci.2006.05.003	Allergy; Immunology
Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. This review focuses on advances and updates in the epidemiology, pathogenesis, diagnosis, and treatment of food allergy over the past 3 years since our last comprehensive review. On the basis of numerous studies, food allergy likely affects nearly 5% of adults and 8% of children, with growing evidence of an increase in prevalence. Potentially rectifiable risk factors include vitamin D insufficiency, unhealthful dietary fat, obesity, increased hygiene, and the timing of exposure to foods, but genetics and other lifestyle issues play a role as well. Interesting clinical insights into pathogenesis include discoveries regarding gene-environment interactions and an increasing understanding of the role of nonoral sensitizing exposures causing food allergy, such as delayed allergic reactions to carbohydrate moieties in mammalian meats caused by sensitization from homologous substances transferred during tick bites. Component-resolved diagnosis is being rapidly incorporated into clinical use, and sophisticated diagnostic tests that indicate severity and prognosis are on the horizon. Current management relies heavily on avoidance and emergency preparedness, and recent studies, guidelines, and resources provide insight into improving the safety and well-being of patients and their families. Incorporation of extensively heated (heat-denatured) forms of milk and egg into the diets of children who tolerate these foods, rather than strict avoidance, represents a significant shift in clinical approach. Recommendations about the prevention of food allergy and atopic disease through diet have changed radically, with rescinding of many recommendations about extensive and prolonged allergen avoidance. Numerous therapies have reached clinical trials, with some showing promise to dramatically alter treatment. Ongoing studies will elucidate improved prevention, diagnosis, and treatment.. food allergy| food hypersensitivity| oral tolerance| gastrointestinal food hypersensitivity| food allergens| anaphylaxis|skin prick test| cows milk allergy| red meat allergy| quality-of-life| ara h 2| induced enterocolitis syndrome| prospective birth cohort| long-term outcomes| peanut allergy| egg allergy.	FEB-2014	food allergy| food hypersensitivity| oral tolerance| gastrointestinal food hypersensitivity| food allergens| anaphylaxis|skin prick test| cows milk allergy| red meat allergy| quality-of-life| ara h 2| induced enterocolitis syndrome| prospective birth cohort| long-term outcomes| peanut allergy| egg allergy	Sicherer, SH; Sampson, HA	Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Food allergy; food hypersensitivity; oral tolerance; gastrointestinal food hypersensitivity; food allergens; anaphylaxis	SKIN PRICK TEST; COWS MILK ALLERGY; RED MEAT ALLERGY; QUALITY-OF-LIFE; ARA H 2; INDUCED ENTEROCOLITIS SYNDROME; PROSPECTIVE BIRTH COHORT; LONG-TERM OUTCOMES; PEANUT ALLERGY; EGG ALLERGY	This review focuses on advances and updates in the epidemiology, pathogenesis, diagnosis, and treatment of food allergy over the past 3 years since our last comprehensive review. On the basis of numerous studies, food allergy likely affects nearly 5% of adults and 8% of children, with growing evidence of an increase in prevalence. Potentially rectifiable risk factors include vitamin D insufficiency, unhealthful dietary fat, obesity, increased hygiene, and the timing of exposure to foods, but genetics and other lifestyle issues play a role as well. Interesting clinical insights into pathogenesis include discoveries regarding gene-environment interactions and an increasing understanding of the role of nonoral sensitizing exposures causing food allergy, such as delayed allergic reactions to carbohydrate moieties in mammalian meats caused by sensitization from homologous substances transferred during tick bites. Component-resolved diagnosis is being rapidly incorporated into clinical use, and sophisticated diagnostic tests that indicate severity and prognosis are on the horizon. Current management relies heavily on avoidance and emergency preparedness, and recent studies, guidelines, and resources provide insight into improving the safety and well-being of patients and their families. Incorporation of extensively heated (heat-denatured) forms of milk and egg into the diets of children who tolerate these foods, rather than strict avoidance, represents a significant shift in clinical approach. Recommendations about the prevention of food allergy and atopic disease through diet have changed radically, with rescinding of many recommendations about extensive and prolonged allergen avoidance. Numerous therapies have reached clinical trials, with some showing promise to dramatically alter treatment. Ongoing studies will elucidate improved prevention, diagnosis, and treatment.	199	275	2014	22	10.1016/j.jaci.2013.11.020	Allergy; Immunology
Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial. Background Some patients wit chronic obstructive pulmonary disease (COPD) respond toe corticosteroid therapy. Whether these patients have different airway pathology from other COPD patients is unclear. We tested the hypothesis that response to prednisolone is related to the presence of eosinophilic airway inflammation. Methods We did a randomised, double-blind, crossover trial. Patients who had COPD treated with bronchodilators only were assigned placebo and 30 mg prednisolone daily for 2 weeks each, in a random order, separated by a 4-week washout period. Before and after each treatment period, we assessed patients with spirometry, symptom scores, the chronic respiratory disease questionnaire (CRQ), incremental shuttle walk test, and induced sputum. Analysis was done by intention to treat. Findings 83 patients were recruited, of whom 67 were randomised. The geometric mean sputum eosinophil count fell significantly after prednisolone (from 2.4% to 0.4%; mean difference six-fold [95% CI 3.1-11.4]) but not after placebo. Other sputum cell counts did not change. After stratification into tertiles by baseline eosinophil count, postbronchodilator forced expiratory volume in 1 s (FEV1) and total scores on the CRQ improved progressively after prednisolone from the lowest to the highest eosinophilic tertile, compared with placebo. The mean change in postbronchodilator FEV1, total CRQ score, and shuttle walk distance with prednisolone compared with placebo in the highest tertile was 0.19 L (0.06-0.32), 0.62 (0.31-0.93), and 20 m (5-35), respectively. Interpretation Our findings suggest that eosinophilic airway inflammation contributes to airflow obstruction and symptoms in some patients with COPD and that the short-term effects of prednisolone are due to modification of this feature of the inflammatory response. The possibility that sputum eosinophilia identifies a subgroup of patients who particularly respond to long-term treatment with inhaled corticosteroids should be investigated.. air-flow obstruction| inhaled corticosteroids| airways obstruction| chronic-bronchitis| asthma| inflammation| smokers| copd| budesonide| mild.	OCT 28-2000	air-flow obstruction| inhaled corticosteroids| airways obstruction| chronic-bronchitis| asthma| inflammation| smokers| copd| budesonide| mild	Brightling, CE; Monteiro, W; Ward, R; Parker, D; Morgan, MDL; Wardlaw, AJ; Pavord, ID	Sputum eosinophilia and short-term response to prednisolone in chronic obstructive pulmonary disease: a randomised controlled trial		LANCET		AIR-FLOW OBSTRUCTION; INHALED CORTICOSTEROIDS; AIRWAYS OBSTRUCTION; CHRONIC-BRONCHITIS; ASTHMA; INFLAMMATION; SMOKERS; COPD; BUDESONIDE; MILD	Background Some patients wit chronic obstructive pulmonary disease (COPD) respond toe corticosteroid therapy. Whether these patients have different airway pathology from other COPD patients is unclear. We tested the hypothesis that response to prednisolone is related to the presence of eosinophilic airway inflammation. Methods We did a randomised, double-blind, crossover trial. Patients who had COPD treated with bronchodilators only were assigned placebo and 30 mg prednisolone daily for 2 weeks each, in a random order, separated by a 4-week washout period. Before and after each treatment period, we assessed patients with spirometry, symptom scores, the chronic respiratory disease questionnaire (CRQ), incremental shuttle walk test, and induced sputum. Analysis was done by intention to treat. Findings 83 patients were recruited, of whom 67 were randomised. The geometric mean sputum eosinophil count fell significantly after prednisolone (from 2.4% to 0.4%; mean difference six-fold [95% CI 3.1-11.4]) but not after placebo. Other sputum cell counts did not change. After stratification into tertiles by baseline eosinophil count, postbronchodilator forced expiratory volume in 1 s (FEV1) and total scores on the CRQ improved progressively after prednisolone from the lowest to the highest eosinophilic tertile, compared with placebo. The mean change in postbronchodilator FEV1, total CRQ score, and shuttle walk distance with prednisolone compared with placebo in the highest tertile was 0.19 L (0.06-0.32), 0.62 (0.31-0.93), and 20 m (5-35), respectively. Interpretation Our findings suggest that eosinophilic airway inflammation contributes to airflow obstruction and symptoms in some patients with COPD and that the short-term effects of prednisolone are due to modification of this feature of the inflammatory response. The possibility that sputum eosinophilia identifies a subgroup of patients who particularly respond to long-term treatment with inhaled corticosteroids should be investigated.	29	275	2000	6	10.1016/S0140-6736(00)02872-5	General & Internal Medicine
The airway epithelium in asthma. Asthma is a T lymphocyte-controlled disease of the airway wall caused by inflammation, overproduction of mucus and airway wall remodeling leading to bronchial hyperreactivity and airway obstruction. The airway epithelium is considered an essential controller of inflammatory, immune and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. Epithelial cells express pattern recognition receptors that detect environmental stimuli and secrete endogenous danger signals, thereby activating dendritic cells and bridging innate and adaptive immunity. Improved understanding of the epithelium's function in maintaining the integrity of the airways and its dysfunction in asthma has provided important mechanistic insight into how asthma is initiated and perpetuated and could provide a framework by which to select new therapeutic strategies that prevent exacerbations and alter the natural course of the disease.. house-dust mite| thymic stromal lymphopoietin| respiratory syncytial virus| epidermal-growth-factor| protease-activated receptor-2| inflammatory dendritic cells| allergic lung inflammation| innate immune-responses| factor-kappa-b| in-vivo.	MAY-2012	house-dust mite| thymic stromal lymphopoietin| respiratory syncytial virus| epidermal-growth-factor| protease-activated receptor-2| inflammatory dendritic cells| allergic lung inflammation| innate immune-responses| factor-kappa-b| in-vivo	Lambrecht, BN; Hammad, H	The airway epithelium in asthma		NATURE MEDICINE		HOUSE-DUST MITE; THYMIC STROMAL LYMPHOPOIETIN; RESPIRATORY SYNCYTIAL VIRUS; EPIDERMAL-GROWTH-FACTOR; PROTEASE-ACTIVATED RECEPTOR-2; INFLAMMATORY DENDRITIC CELLS; ALLERGIC LUNG INFLAMMATION; INNATE IMMUNE-RESPONSES; FACTOR-KAPPA-B; IN-VIVO	Asthma is a T lymphocyte-controlled disease of the airway wall caused by inflammation, overproduction of mucus and airway wall remodeling leading to bronchial hyperreactivity and airway obstruction. The airway epithelium is considered an essential controller of inflammatory, immune and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. Epithelial cells express pattern recognition receptors that detect environmental stimuli and secrete endogenous danger signals, thereby activating dendritic cells and bridging innate and adaptive immunity. Improved understanding of the epithelium's function in maintaining the integrity of the airways and its dysfunction in asthma has provided important mechanistic insight into how asthma is initiated and perpetuated and could provide a framework by which to select new therapeutic strategies that prevent exacerbations and alter the natural course of the disease.	156	273	2012	9	10.1038/nm.2737	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Air pollution and children's health. Children's exposure to air pollution is a special concern because their immune system and lungs are not fully developed when exposure begins, raising the possibility of different responses than seen in adults. In addition, children spend more time outside, where the concentrations of pollution from traffic, powerplants, and other combustion sources are generally higher. Although air pollution has long been thought to exacerbate minor acute illnesses, recent studies have suggested that air pollution, particularly traffic-related pollution, is associated with infant mortality and the development of asthma and atopy. Other studies have associated particulate air pollution with acute bronchitis in children and demonstrated that rates of bronchitis and chronic cough declined in areas where particle concentrations have fallen. More mixed results have been reported for lung function. Overall, evidence for effects of air pollution on children have been growing, and effects are seen at concentrations that are common today. Although many of these associations seem likely to be causal, others require and warrant additional investigation.. asthma| particles| ozone| lung reaction|low-birth-weight| peak expiratory flow| exhaled nitric-oxide| lung-function growth| respiratory symptoms| particulate matter| southern california| pulmonary-function| infant-mortality| childhood asthma.	APR 1-2004	asthma| particles| ozone| lung reaction|low-birth-weight| peak expiratory flow| exhaled nitric-oxide| lung-function growth| respiratory symptoms| particulate matter| southern california| pulmonary-function| infant-mortality| childhood asthma	Schwartz, J	Air pollution and children's health		PEDIATRICS	asthma; particles; ozone; lung reaction	LOW-BIRTH-WEIGHT; PEAK EXPIRATORY FLOW; EXHALED NITRIC-OXIDE; LUNG-FUNCTION GROWTH; RESPIRATORY SYMPTOMS; PARTICULATE MATTER; SOUTHERN CALIFORNIA; PULMONARY-FUNCTION; INFANT-MORTALITY; CHILDHOOD ASTHMA	Children's exposure to air pollution is a special concern because their immune system and lungs are not fully developed when exposure begins, raising the possibility of different responses than seen in adults. In addition, children spend more time outside, where the concentrations of pollution from traffic, powerplants, and other combustion sources are generally higher. Although air pollution has long been thought to exacerbate minor acute illnesses, recent studies have suggested that air pollution, particularly traffic-related pollution, is associated with infant mortality and the development of asthma and atopy. Other studies have associated particulate air pollution with acute bronchitis in children and demonstrated that rates of bronchitis and chronic cough declined in areas where particle concentrations have fallen. More mixed results have been reported for lung function. Overall, evidence for effects of air pollution on children have been growing, and effects are seen at concentrations that are common today. Although many of these associations seem likely to be causal, others require and warrant additional investigation.	90	273	2004	7		Pediatrics
Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey. To date, no international surveys estimating the burden of chronic obstructive pulmonary disease (COPD) in the general population have been published. The Confronting COPD International Survey aimed to quantify morbidity and burden in COPD subjects in 2000. From a total of 201,921 households screened by random-digit dialling in the USA, Canada, France, Italy, Germany, the Netherlands, Spain and the UK, 3,265 subjects with a diagnosis of COPD, chronic bronchitis or emphysema, or with symptoms of chronic bronchitis, were identified. The mean age of the subjects was 63.3 yrs and 44.2%) were female. Subjects with COPD in North America and Europe appear to underestimate their morbidity, as shown by the high proportion of subjects with limitations to their basic daily life activities, frequent work loss (45.3% of COPD subjects of <65 yrs reported work loss in the past year) and frequent use of health services (13.8%. of subjects required emergency care in the last year), and may be undertreated. There was a significant disparity between subjects' perception of disease severity and the degree of severity indicated by an objective breathlessness scale. Of those with the most severe breathlessness (too breathless to leave the house), 35.8%, described their condition as mild or moderate, as did 60.3% of those with the next most severe degree of breathlessness (breathless after walking a few minutes on level ground). This international survey confirmed the great burden to society and high individual morbidity associated with chronic obstructive pulmonary disease in subjects in North America and Europe.. chronic obstructive pulmonary disease| epidemiology| guidelines| management| subject perspective|obstructive pulmonary-disease| economic burden| united-states| lung-function| asthma| health| epidemiology| adults| risk| exacerbations.	OCT-2002	chronic obstructive pulmonary disease| epidemiology| guidelines| management| subject perspective|obstructive pulmonary-disease| economic burden| united-states| lung-function| asthma| health| epidemiology| adults| risk| exacerbations	Rennard, S; Decramer, M; Calverley, PMA; Pride, NB; Soriano, JB; Vermeire, PA; Vestbo, J	Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey		EUROPEAN RESPIRATORY JOURNAL	chronic obstructive pulmonary disease; epidemiology; guidelines; management; subject perspective	OBSTRUCTIVE PULMONARY-DISEASE; ECONOMIC BURDEN; UNITED-STATES; LUNG-FUNCTION; ASTHMA; HEALTH; EPIDEMIOLOGY; ADULTS; RISK; EXACERBATIONS	To date, no international surveys estimating the burden of chronic obstructive pulmonary disease (COPD) in the general population have been published. The Confronting COPD International Survey aimed to quantify morbidity and burden in COPD subjects in 2000. From a total of 201,921 households screened by random-digit dialling in the USA, Canada, France, Italy, Germany, the Netherlands, Spain and the UK, 3,265 subjects with a diagnosis of COPD, chronic bronchitis or emphysema, or with symptoms of chronic bronchitis, were identified. The mean age of the subjects was 63.3 yrs and 44.2%) were female. Subjects with COPD in North America and Europe appear to underestimate their morbidity, as shown by the high proportion of subjects with limitations to their basic daily life activities, frequent work loss (45.3% of COPD subjects of <65 yrs reported work loss in the past year) and frequent use of health services (13.8%. of subjects required emergency care in the last year), and may be undertreated. There was a significant disparity between subjects' perception of disease severity and the degree of severity indicated by an objective breathlessness scale. Of those with the most severe breathlessness (too breathless to leave the house), 35.8%, described their condition as mild or moderate, as did 60.3% of those with the next most severe degree of breathlessness (breathless after walking a few minutes on level ground). This international survey confirmed the great burden to society and high individual morbidity associated with chronic obstructive pulmonary disease in subjects in North America and Europe.	33	273	2002	7	10.1183/09031936.02.03242002	Respiratory System
The mechanism of exercise-induced asthma is .... Exercise-induced asthma (EIA) refers to the transient narrowing of the airways that follows vigorous exercise. The mechanism whereby EIA occurs is thought to relate to the consequences of heating and humidifying large volumes of air during exercise. In 1978 airway cooling was identified as an important stimulus for EIA; however, severe EIA also occurred when hot dry air was inspired, and there was no abnormal cooling of the airways. In 1986 the thermal hypothesis proposed that cooling of the airways needed to be followed by rapid rewarming and that these two events caused a vasoconstriction and a reactive hyperemia of the bronchial microcirculation, together with edema of the airway wall, causing the airways to narrow after exercise. The osmotic, or airway-drying, hypothesis developed from 1982-1992 because neither airway cooling nor rewarming appeared to be necessary for EIA to occur. As water is evaporated from the airway surface liquid, it becomes hyperosmolar and provides an osmotic stimulus for water to move from any cell nearby, resulting in cell volume loss. It is proposed that the regulatory volume increase, after cell shrinkage, is the key event resulting in release of inflammatory mediators that cause airway smooth muscle to contract and the airways of asthmatic subjects to narrow. This event may or may not be associated with airway edema. The osmotic and thermal theories come together by considering that inspiration of cold air not only cools the airways but also increases the numbers of airway generations becoming dehydrated in the humidifying process.. exercise| airway cooling| airway drying| osmolarity| respiratory water loss|canine peripheral airways| thermally-induced asthma| bronchial blood-flow| dry air| isocapnic hyperventilation| mucociliary clearance| water-loss| hypertonic saline| respiratory-tract| healthy-subjects.	SEP-2000	exercise| airway cooling| airway drying| osmolarity| respiratory water loss|canine peripheral airways| thermally-induced asthma| bronchial blood-flow| dry air| isocapnic hyperventilation| mucociliary clearance| water-loss| hypertonic saline| respiratory-tract| healthy-subjects	Anderson, SD; Daviskas, E	The mechanism of exercise-induced asthma is ...		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	exercise; airway cooling; airway drying; osmolarity; respiratory water loss	CANINE PERIPHERAL AIRWAYS; THERMALLY-INDUCED ASTHMA; BRONCHIAL BLOOD-FLOW; DRY AIR; ISOCAPNIC HYPERVENTILATION; MUCOCILIARY CLEARANCE; WATER-LOSS; HYPERTONIC SALINE; RESPIRATORY-TRACT; HEALTHY-SUBJECTS	Exercise-induced asthma (EIA) refers to the transient narrowing of the airways that follows vigorous exercise. The mechanism whereby EIA occurs is thought to relate to the consequences of heating and humidifying large volumes of air during exercise. In 1978 airway cooling was identified as an important stimulus for EIA; however, severe EIA also occurred when hot dry air was inspired, and there was no abnormal cooling of the airways. In 1986 the thermal hypothesis proposed that cooling of the airways needed to be followed by rapid rewarming and that these two events caused a vasoconstriction and a reactive hyperemia of the bronchial microcirculation, together with edema of the airway wall, causing the airways to narrow after exercise. The osmotic, or airway-drying, hypothesis developed from 1982-1992 because neither airway cooling nor rewarming appeared to be necessary for EIA to occur. As water is evaporated from the airway surface liquid, it becomes hyperosmolar and provides an osmotic stimulus for water to move from any cell nearby, resulting in cell volume loss. It is proposed that the regulatory volume increase, after cell shrinkage, is the key event resulting in release of inflammatory mediators that cause airway smooth muscle to contract and the airways of asthmatic subjects to narrow. This event may or may not be associated with airway edema. The osmotic and thermal theories come together by considering that inspiration of cold air not only cools the airways but also increases the numbers of airway generations becoming dehydrated in the humidifying process.	50	272	2000	7		Allergy; Immunology
Inflammatory dendritic cells-not basophils-are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen. It is unclear how Th2 immunity is induced in response to allergens like house dust mite (HDM). Here, we show that HDM inhalation leads to the TLR4/MyD88-dependent recruitment of IL-4 competent basophils and eosinophils, and of inflammatory DCs to the draining mediastinal nodes. Depletion of basophils only partially reduced Th2 immunity, and depletion of eosinophils had no effect on the Th2 response. Basophils did not take up inhaled antigen, present it to T cells, or express antigen presentation machinery, whereas a population of FceRI(+) DCs readily did. Inflammatory DCs were necessary and sufficient for induction of Th2 immunity and features of asthma, whereas basophils were not required. We favor a model whereby DCs initiate and basophils amplify Th2 immunity to HDM allergen.. eosinophilic airway inflammation| in-vivo depletion| cd4(+) t-cells| type-2 immunity| cutting edge| lymph-nodes| adaptive immunity| il-4 production| steady-state| responses.	SEP 27-2010	eosinophilic airway inflammation| in-vivo depletion| cd4(+) t-cells| type-2 immunity| cutting edge| lymph-nodes| adaptive immunity| il-4 production| steady-state| responses	Hammad, H; Plantinga, M; Deswarte, K; Pouliot, P; Willart, MAM; Kool, M; Muskens, F; Lambrecht, BN	Inflammatory dendritic cells-not basophils-are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen		JOURNAL OF EXPERIMENTAL MEDICINE		EOSINOPHILIC AIRWAY INFLAMMATION; IN-VIVO DEPLETION; CD4(+) T-CELLS; TYPE-2 IMMUNITY; CUTTING EDGE; LYMPH-NODES; ADAPTIVE IMMUNITY; IL-4 PRODUCTION; STEADY-STATE; RESPONSES	It is unclear how Th2 immunity is induced in response to allergens like house dust mite (HDM). Here, we show that HDM inhalation leads to the TLR4/MyD88-dependent recruitment of IL-4 competent basophils and eosinophils, and of inflammatory DCs to the draining mediastinal nodes. Depletion of basophils only partially reduced Th2 immunity, and depletion of eosinophils had no effect on the Th2 response. Basophils did not take up inhaled antigen, present it to T cells, or express antigen presentation machinery, whereas a population of FceRI(+) DCs readily did. Inflammatory DCs were necessary and sufficient for induction of Th2 immunity and features of asthma, whereas basophils were not required. We favor a model whereby DCs initiate and basophils amplify Th2 immunity to HDM allergen.	68	269	2010	15	10.1084/jem.20101563	Immunology; Research & Experimental Medicine
Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Background: Specific oral tolerance induction (SOTI) seems to be a promising treatment of food allergy. Specific oral tolerance induction and elimination diet were compared with respect to efficacy rate and patterns of clinical reaction. Methods: Children with challenge proven immunoglobulin E (IgE)-mediated cow's milk (CM) allergy or hen's egg (HE) allergy were randomly assigned to SOTI or elimination diet as a control group. Specific oral tolerance induction treatment was performed at home on a daily basis according to a study protocol with fresh CM or lyophilized HE protein. Re-evaluation of clinically relevant food allergy was performed by food challenge after a median of 21 months. Children in the SOTI group received a secondary elimination diet for 2 months prior to follow-up challenge to evaluate persistence of induced oral tolerance. Results: At follow-up challenge, nine of 25 children (36%) showed permanent tolerance in the SOTI group, three of 25 (12%) were tolerant with regular intake and four of 25 (16%) were partial responders. In the control group, seven of 20 children (35%) were tolerant. Allergen-specific immunoglobulin E decreased significantly both in children who developed natural tolerance during the elimination diet (P < 0.05) and in those with SOTI (P < 0.001). Conclusions: Specific oral tolerance induction seems a valid treatment option for patients with persistent food allergy. Indications may be given if avoidance cannot be guaranteed or for those who are eager to eat the food in question. Advantages of SOTI are the increased threshold dose for allergic reactions and the substantially reduced risk of severe allergic reactions after inadvertent ingestion of the allergen. However, careful monitoring during SOTI is mandatory.. children| food allergy| specific oral tolerance induction|exercise-induced anaphylaxis| peanut allergy| cows milk| rush desensitization| egg allergy| hypersensitivity| immunotherapy| population| prevalence| sensitization.	NOV-2007	children| food allergy| specific oral tolerance induction|exercise-induced anaphylaxis| peanut allergy| cows milk| rush desensitization| egg allergy| hypersensitivity| immunotherapy| population| prevalence| sensitization	Staden, U; Rolinck-Werninghaus, C; Brewe, F; Wahn, U; Niggemann, B; Beyer, K	Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction		ALLERGY	children; food allergy; specific oral tolerance induction	EXERCISE-INDUCED ANAPHYLAXIS; PEANUT ALLERGY; COWS MILK; RUSH DESENSITIZATION; EGG ALLERGY; HYPERSENSITIVITY; IMMUNOTHERAPY; POPULATION; PREVALENCE; SENSITIZATION	Background: Specific oral tolerance induction (SOTI) seems to be a promising treatment of food allergy. Specific oral tolerance induction and elimination diet were compared with respect to efficacy rate and patterns of clinical reaction. Methods: Children with challenge proven immunoglobulin E (IgE)-mediated cow's milk (CM) allergy or hen's egg (HE) allergy were randomly assigned to SOTI or elimination diet as a control group. Specific oral tolerance induction treatment was performed at home on a daily basis according to a study protocol with fresh CM or lyophilized HE protein. Re-evaluation of clinically relevant food allergy was performed by food challenge after a median of 21 months. Children in the SOTI group received a secondary elimination diet for 2 months prior to follow-up challenge to evaluate persistence of induced oral tolerance. Results: At follow-up challenge, nine of 25 children (36%) showed permanent tolerance in the SOTI group, three of 25 (12%) were tolerant with regular intake and four of 25 (16%) were partial responders. In the control group, seven of 20 children (35%) were tolerant. Allergen-specific immunoglobulin E decreased significantly both in children who developed natural tolerance during the elimination diet (P < 0.05) and in those with SOTI (P < 0.001). Conclusions: Specific oral tolerance induction seems a valid treatment option for patients with persistent food allergy. Indications may be given if avoidance cannot be guaranteed or for those who are eager to eat the food in question. Advantages of SOTI are the increased threshold dose for allergic reactions and the substantially reduced risk of severe allergic reactions after inadvertent ingestion of the allergen. However, careful monitoring during SOTI is mandatory.	33	268	2007	9	10.1111/j.1398-9995.2007.01501.x	Allergy; Immunology
Aspergillus flavus: human pathogen, allergen and mycotoxin producer. Aspergillus infections have grown in importance in the last years. However, most of the studies have focused on Aspergillus fumigatus, the most prevalent species in the genus. In certain locales and hospitals, Aspergillus flavus is more common in air than A. fumigatus, for unclear reasons. After A. fumigatus, A. flavus is the second leading cause of invasive aspergillosis and it is the most common cause of superficial infection. Experimental invasive infections in mice show A. flavus to be 100-fold more virulent than A. fumigatus in terms of inoculum required. Particularly common clinical syndromes associated with A. flavus include chronic granulonnatous sinusitis, keratitis, cutaneous aspergillosis, wound infections and osteomyelitis following trauma and inoculation. Outbreaks associated with A. flavus appear to be associated with single or closely related strains, in contrast to those associated with A. fumigatus. In addition, A. flavus produces aflatoxins, the most toxic and potent hepatocarcinogenic natural compounds ever characterized. Accurate species identification within Aspergillus flavus complex remains difficult due to overlapping morphological and biochemical characteristics, and much taxonomic and population genetics work is necessary to better understand the species and related species. The flavus complex currently includes 23 species or varieties, including two sexual species, Petromyces alliaceus and P. albertensis. The genome of the highly related Aspergillus oryzae is completed and available; that of A. flavus in the final stages of annotation. Our understanding of A. flavus lags far behind that of A. fumigatus. Studies of the genomics, taxonomy, population genetics, pathogenicity, allergenicity and antifungal susceptibility of A. flavus are all required.. primary cutaneous aspergillosis| paranasal sinus mycoses| hematopoietic stem-cell| intensive-care-unit| in-vitro activities| air-borne fungi| invasive aspergillosis| amphotericin-b| section flavi| bronchopulmonary aspergillosis.	JUN-2007	primary cutaneous aspergillosis| paranasal sinus mycoses| hematopoietic stem-cell| intensive-care-unit| in-vitro activities| air-borne fungi| invasive aspergillosis| amphotericin-b| section flavi| bronchopulmonary aspergillosis	Hedayati, MT; Pasqualotto, AC; Warn, PA; Bowyer, P; Denning, DW	Aspergillus flavus: human pathogen, allergen and mycotoxin producer		MICROBIOLOGY-SGM		PRIMARY CUTANEOUS ASPERGILLOSIS; PARANASAL SINUS MYCOSES; HEMATOPOIETIC STEM-CELL; INTENSIVE-CARE-UNIT; IN-VITRO ACTIVITIES; AIR-BORNE FUNGI; INVASIVE ASPERGILLOSIS; AMPHOTERICIN-B; SECTION FLAVI; BRONCHOPULMONARY ASPERGILLOSIS	Aspergillus infections have grown in importance in the last years. However, most of the studies have focused on Aspergillus fumigatus, the most prevalent species in the genus. In certain locales and hospitals, Aspergillus flavus is more common in air than A. fumigatus, for unclear reasons. After A. fumigatus, A. flavus is the second leading cause of invasive aspergillosis and it is the most common cause of superficial infection. Experimental invasive infections in mice show A. flavus to be 100-fold more virulent than A. fumigatus in terms of inoculum required. Particularly common clinical syndromes associated with A. flavus include chronic granulonnatous sinusitis, keratitis, cutaneous aspergillosis, wound infections and osteomyelitis following trauma and inoculation. Outbreaks associated with A. flavus appear to be associated with single or closely related strains, in contrast to those associated with A. fumigatus. In addition, A. flavus produces aflatoxins, the most toxic and potent hepatocarcinogenic natural compounds ever characterized. Accurate species identification within Aspergillus flavus complex remains difficult due to overlapping morphological and biochemical characteristics, and much taxonomic and population genetics work is necessary to better understand the species and related species. The flavus complex currently includes 23 species or varieties, including two sexual species, Petromyces alliaceus and P. albertensis. The genome of the highly related Aspergillus oryzae is completed and available; that of A. flavus in the final stages of annotation. Our understanding of A. flavus lags far behind that of A. fumigatus. Studies of the genomics, taxonomy, population genetics, pathogenicity, allergenicity and antifungal susceptibility of A. flavus are all required.	172	268	2007	16	10.1099/mic.0.2007/007641-0	Microbiology
"Broken windows and the risk of gonorrhea. Objectives. We examined the relationships between neighborhood conditions and gonorrhea. Methods. We assessed 55 block soups by rating housing and street conditions. We mapped all cases of gonorrhea between 1994 and 1996 and calculated aggregated case rates by block group. We obtained public school inspection reports and assigned findings to the block groups served by the neighborhood schools. A ""broken windows"" index measured housing quality, abandoned cars, graffiti: trash and public school deterioration. Using data from the 1990 census and 1995 updates, we determined the association between ""broken windows,"" demographic characteristics, and gonorrhea rates. Results. The broken windows index explained more of the variance in gonorrhea rates than did a poverty index measuring: income, unemployment, and low education. in high-poverty neighborhoods, block groups with high broken windows scores had significantly higher gonorrhea rates than block groups with low broken windows scores(46.6 per 1000 vs 25.8 per 1000; P<.001). Conclusions. The robust association of deteriorated physical conditions of local neighborhoods with gonorrhea rates, independent of poverty, merits an intervention trial to test whether the environment has a, causal role in influencing high-risk sexual behaviors.. sexually-transmitted diseases| united-states population| cockroach allergen| drug-use| health| syphilis| behavior| children| alcohol| neighborhoods."	FEB-2000	sexually-transmitted diseases| united-states population| cockroach allergen| drug-use| health| syphilis| behavior| children| alcohol| neighborhoods	Cohen, D; Spear, S; Scribner, R; Kissinger, P; Mason, K; Wildgen, J	Broken windows and the risk of gonorrhea		AMERICAN JOURNAL OF PUBLIC HEALTH		SEXUALLY-TRANSMITTED DISEASES; UNITED-STATES POPULATION; COCKROACH ALLERGEN; DRUG-USE; HEALTH; SYPHILIS; BEHAVIOR; CHILDREN; ALCOHOL; NEIGHBORHOODS	"Objectives. We examined the relationships between neighborhood conditions and gonorrhea. Methods. We assessed 55 block soups by rating housing and street conditions. We mapped all cases of gonorrhea between 1994 and 1996 and calculated aggregated case rates by block group. We obtained public school inspection reports and assigned findings to the block groups served by the neighborhood schools. A ""broken windows"" index measured housing quality, abandoned cars, graffiti: trash and public school deterioration. Using data from the 1990 census and 1995 updates, we determined the association between ""broken windows,"" demographic characteristics, and gonorrhea rates. Results. The broken windows index explained more of the variance in gonorrhea rates than did a poverty index measuring: income, unemployment, and low education. in high-poverty neighborhoods, block groups with high broken windows scores had significantly higher gonorrhea rates than block groups with low broken windows scores(46.6 per 1000 vs 25.8 per 1000; P<.001). Conclusions. The robust association of deteriorated physical conditions of local neighborhoods with gonorrhea rates, independent of poverty, merits an intervention trial to test whether the environment has a, causal role in influencing high-risk sexual behaviors."	51	267	2000	7	10.2105/AJPH.90.2.230	Public, Environmental & Occupational Health
An Official American Thoracic Society Public Policy Statement: Novel Risk Factors and the Global Burden of Chronic Obstructive Pulmonary Disease. Rationale: Although cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD), a substantial proportion of COPD cases cannot be explained by smoking alone. Objectives: To evaluate the risk factors for COPD besides personal cigarette smoking. Methods: We constituted an ad hoc subcommittee of the American Thoracic Society Environmental and Occupational Health Assembly. An international group of members was invited, based on their scientific expertise in a specific risk factor for COPD. For each risk factor area, the committee reviewed the literature, summarized the evidence, and developed conclusions about the likelihood of it causing COPD. All conclusions were based on unanimous consensus. Measurements and Main Results: The population-attributable fraction for smoking as a cause of COPD ranged from 9.7 to 97.9%, but was less than 80% in most studies, indicating a substantial burden of disease attributable to nonsmoking risk factors. On the basis of our review, we concluded that specific genetic syndromes and occupational exposures were causally related to the development of COPD. Traffic and other outdoor pollution, secondhand smoke, biomass smoke, and dietary factors are associated with COPD, but sufficient criteria for causation were not met. Chronic asthma and tuberculosis are associated with irreversible loss of lung function, but there remains uncertainty about whether there are important phenotypic differences compared with COPD as it is typically encountered in clinical settings. Conclusions: In public health terms, a substantive burden of COPD is attributable to risk factors other than smoking. To prevent COPD-related disability and mortality, efforts must focus on prevention and cessation of exposure to smoking and these other, less well-recognized risk factors.. pulmonary disease, chronic obstructive| pulmonary emphysema| chronic bronchitis| respiratory function tests| genetics| diet| asthma| air pollution| air pollution, indoor| tobacco smoke pollution| biomass| occupational exposure| occupational diseases| diet| nutritional status| tuberculosis|air-flow obstruction| lung-function decline| chronic respiratory symptoms| 3rd national-health| nutrition examination survey| environmental tobacco-smoke| hogg-dube-syndrome| severe alpha(1)-antitrypsin deficiency| resolution computed-tomography| southern california children.	SEP 1-2010	pulmonary disease, chronic obstructive| pulmonary emphysema| chronic bronchitis| respiratory function tests| genetics| diet| asthma| air pollution| air pollution, indoor| tobacco smoke pollution| biomass| occupational exposure| occupational diseases| diet| nutritional status| tuberculosis|air-flow obstruction| lung-function decline| chronic respiratory symptoms| 3rd national-health| nutrition examination survey| environmental tobacco-smoke| hogg-dube-syndrome| severe alpha(1)-antitrypsin deficiency| resolution computed-tomography| southern california children	Eisner, MD; Anthonisen, N; Coultas, D; Kuenzli, N; Perez-Padilla, R; Postma, D; Romieu, I; Silverman, EK; Balmes, JR	An Official American Thoracic Society Public Policy Statement: Novel Risk Factors and the Global Burden of Chronic Obstructive Pulmonary Disease		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	pulmonary disease, chronic obstructive; pulmonary emphysema; chronic bronchitis; respiratory function tests; genetics; diet; asthma; air pollution; air pollution, indoor; tobacco smoke pollution; biomass; occupational exposure; occupational diseases; diet; nutritional status; tuberculosis	AIR-FLOW OBSTRUCTION; LUNG-FUNCTION DECLINE; CHRONIC RESPIRATORY SYMPTOMS; 3RD NATIONAL-HEALTH; NUTRITION EXAMINATION SURVEY; ENVIRONMENTAL TOBACCO-SMOKE; HOGG-DUBE-SYNDROME; SEVERE ALPHA(1)-ANTITRYPSIN DEFICIENCY; RESOLUTION COMPUTED-TOMOGRAPHY; SOUTHERN CALIFORNIA CHILDREN	Rationale: Although cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD), a substantial proportion of COPD cases cannot be explained by smoking alone. Objectives: To evaluate the risk factors for COPD besides personal cigarette smoking. Methods: We constituted an ad hoc subcommittee of the American Thoracic Society Environmental and Occupational Health Assembly. An international group of members was invited, based on their scientific expertise in a specific risk factor for COPD. For each risk factor area, the committee reviewed the literature, summarized the evidence, and developed conclusions about the likelihood of it causing COPD. All conclusions were based on unanimous consensus. Measurements and Main Results: The population-attributable fraction for smoking as a cause of COPD ranged from 9.7 to 97.9%, but was less than 80% in most studies, indicating a substantial burden of disease attributable to nonsmoking risk factors. On the basis of our review, we concluded that specific genetic syndromes and occupational exposures were causally related to the development of COPD. Traffic and other outdoor pollution, secondhand smoke, biomass smoke, and dietary factors are associated with COPD, but sufficient criteria for causation were not met. Chronic asthma and tuberculosis are associated with irreversible loss of lung function, but there remains uncertainty about whether there are important phenotypic differences compared with COPD as it is typically encountered in clinical settings. Conclusions: In public health terms, a substantive burden of COPD is attributable to risk factors other than smoking. To prevent COPD-related disability and mortality, efforts must focus on prevention and cessation of exposure to smoking and these other, less well-recognized risk factors.	306	265	2010	26	10.1164/rccm.200811-1757ST	General & Internal Medicine; Respiratory System
Mortality from ship emissions: A global assessment. Epidemiological studies consistently link ambient concentrations of particulate matter (PM) to negative health impacts, including asthma, heart attacks, hospital admissions, and premature mortality. We model ambient PM concentrations from oceangoing ships using two geospatial emissions inventories and two global aerosol models. We estimate global and regional mortalities by applying ambient PM increases due to ships to cardiopulmonary and lung cancer concentration-risk functions and population models. Our results indicate that shipping-related PM emissions are responsible for approximately 60,000 cardiopulmonary and lung cancer deaths annually, with most deaths occurring near coastlines in Europe, East Asia, and South Asia. Under current regulation and with the expected growth in shipping activity, we estimate that annual mortalities could increase by 40% by 2012.. air-pollution| ocean| model| health.	DEC 15-2007	air-pollution| ocean| model| health	Corbett, JJ; Winebrake, JJ; Green, EH; Kasibhatla, P; Eyring, V; Lauer, A	Mortality from ship emissions: A global assessment		ENVIRONMENTAL SCIENCE & TECHNOLOGY		AIR-POLLUTION; OCEAN; MODEL; HEALTH	Epidemiological studies consistently link ambient concentrations of particulate matter (PM) to negative health impacts, including asthma, heart attacks, hospital admissions, and premature mortality. We model ambient PM concentrations from oceangoing ships using two geospatial emissions inventories and two global aerosol models. We estimate global and regional mortalities by applying ambient PM increases due to ships to cardiopulmonary and lung cancer concentration-risk functions and population models. Our results indicate that shipping-related PM emissions are responsible for approximately 60,000 cardiopulmonary and lung cancer deaths annually, with most deaths occurring near coastlines in Europe, East Asia, and South Asia. Under current regulation and with the expected growth in shipping activity, we estimate that annual mortalities could increase by 40% by 2012.	32	264	2007	7	10.1021/es071686z	Engineering; Environmental Sciences & Ecology
Roflumilast - an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Background Chronic-obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation associated with chronic inflammation. There are few treatment options for the disease. This study assessed the efficacy and safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate to severe COPD. Methods This phase III, multicentre, double-blind, randomised, placebo-controlled study was undertaken in an outpatient setting. 1411 patients with COPD were randomly assigned roflumilast 250 mu g (n=576), roflumilast 500 mu g (n=555), or placebo (n=280) given orally once daily for 24 weeks. Primary outcomes were postbronchodilator FEV1 and health-related quality of life. Secondary outcomes included other lung function parameters and COPD exacerbations. Analyses were by intention to treat. Findings 1157 (82%) patients completed the study; 32 (11%) withdrew from the placebo group, 100 (17%) from the roflumilast 250 mu g group, and 124 (22%) from the roflumilast 500 mu g group. Postbronchodilator FEV1 at the end of treatment significantly improved with roflumilast 250 mu g (by 74 mL [SD 18]) and roflumilast 500 mu g (by 97 mL [18]) compared with placebo (p<0.0001). Improvement in health-related quality of life was greater with roflumilast 250 mu g (-3.4 units [0.6]) and roflumilast 500 mu g (-3.5 units [0.6]) than with placebo (-1.8 units [0.8]), although the differences between treatment groups were not significant. The mean numbers of exacerbations per patient were 1.13 (2.37), 1.03 (2.33), and 0.75 (1.89) with placebo, roflumilast 250 mu g, and roflumilast 500 mu g, respectively. Most adverse events were mild to moderate in intensity and resolved during the study. Interpretation Roflumilast is a promising candidate for anti-inflammatory COPD treatment because it improved lung function and reduced exacerbations compared with placebo. Long-term studies are needed to fully assess the effect on health-related quality of life.. air-flow limitation| phosphodiesterase-4 inhibitor| pde4 inhibitor| health-status| in-vitro| asthma| copd| burden| fluticasone| salmeterol.	AUG 13-2005	air-flow limitation| phosphodiesterase-4 inhibitor| pde4 inhibitor| health-status| in-vitro| asthma| copd| burden| fluticasone| salmeterol	Rabe, KF; Bateman, ED; O'Donnell, D; Witte, S; Bredenbroker, D; Bethke, TD	Roflumilast - an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial		LANCET		AIR-FLOW LIMITATION; PHOSPHODIESTERASE-4 INHIBITOR; PDE4 INHIBITOR; HEALTH-STATUS; IN-VITRO; ASTHMA; COPD; BURDEN; FLUTICASONE; SALMETEROL	Background Chronic-obstructive pulmonary disease (COPD) is characterised by progressive airflow limitation associated with chronic inflammation. There are few treatment options for the disease. This study assessed the efficacy and safety of roflumilast, a phosphodiesterase-4 inhibitor, in patients with moderate to severe COPD. Methods This phase III, multicentre, double-blind, randomised, placebo-controlled study was undertaken in an outpatient setting. 1411 patients with COPD were randomly assigned roflumilast 250 mu g (n=576), roflumilast 500 mu g (n=555), or placebo (n=280) given orally once daily for 24 weeks. Primary outcomes were postbronchodilator FEV1 and health-related quality of life. Secondary outcomes included other lung function parameters and COPD exacerbations. Analyses were by intention to treat. Findings 1157 (82%) patients completed the study; 32 (11%) withdrew from the placebo group, 100 (17%) from the roflumilast 250 mu g group, and 124 (22%) from the roflumilast 500 mu g group. Postbronchodilator FEV1 at the end of treatment significantly improved with roflumilast 250 mu g (by 74 mL [SD 18]) and roflumilast 500 mu g (by 97 mL [18]) compared with placebo (p<0.0001). Improvement in health-related quality of life was greater with roflumilast 250 mu g (-3.4 units [0.6]) and roflumilast 500 mu g (-3.5 units [0.6]) than with placebo (-1.8 units [0.8]), although the differences between treatment groups were not significant. The mean numbers of exacerbations per patient were 1.13 (2.37), 1.03 (2.33), and 0.75 (1.89) with placebo, roflumilast 250 mu g, and roflumilast 500 mu g, respectively. Most adverse events were mild to moderate in intensity and resolved during the study. Interpretation Roflumilast is a promising candidate for anti-inflammatory COPD treatment because it improved lung function and reduced exacerbations compared with placebo. Long-term studies are needed to fully assess the effect on health-related quality of life.	33	264	2005	9	10.1016/S0140-6736(05)67100-0	General & Internal Medicine
Scientific rationale for inhaled combination therapy with long-acting beta(2)-agonists and corticosteroids. The addition of an inhaled long-acting beta(2)-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients and two fixed combination inhalers (salmeterol/fluticasone and formoterol/budesonide) are increasingly used as a convenient controller in patients with persistent asthma. There is a strong scientific rationale for the combination of these two drug classes. ICS suppress the chronic inflammation of asthma and reduce airway hyperresponsiveness and this is achieved at low doses in most patients. LABA act on different aspects of the pathophysiology of asthma. In addition to their bronchodilator action, LABA also inhibit mast cell mediator release, plasma exudation and may reduce sensory nerve activation. Thus these two classes of drug address complementary aspects of the pathophysiology of asthma that neither drug class is able to achieve alone. There are several positive interactions between LABA and ICS. Corticosteroids increase the expression of beta(2)-receptors by increasing gene transcription. Experimentally this protects against the loss of beta(2)-receptors in response to long-term exposure to beta(2)-agonists. While this is unlikely to be important in bronchodilator responses to beta(2)-agonists, in view of the large beta-receptor reserve, it is probably important in preventing loss of beta-agonist effects on the nonbronchodilator actions of LABA discussed earlier. beta(2)-Agonists may potentiate the molecular mechanism of corticosteroid actions, with increased nuclear localization of glucocorticoid receptors and additive or sometimes synergistic suppression of inflammatory mediator release. Thus LABA and ICS may optimize each others beneficial actions in the airways, but the low systemic effects of these drugs do not result in any increase in adverse effects. Long-acting beta(2)-agonists corticosteroid inhaler therapy is therefore a logical advance and results in effective control of asthma in the majority of patients without significant adverse effects. This simplified approach to long-term asthma therapy has a strong scientific rationale.. asthma| budesonide| fluticasone propionate| formoterol| salmeterol|airway smooth-muscle| lung mast-cells| salmeterol/fluticasone propionate combination| nk2 receptor expression| down-regulation| in-vivo| mu-g| glucocorticoid receptor| adenosine-monophosphate| microvascular leakage.	JAN-2002	asthma| budesonide| fluticasone propionate| formoterol| salmeterol|airway smooth-muscle| lung mast-cells| salmeterol/fluticasone propionate combination| nk2 receptor expression| down-regulation| in-vivo| mu-g| glucocorticoid receptor| adenosine-monophosphate| microvascular leakage	Barnes, PJ	Scientific rationale for inhaled combination therapy with long-acting beta(2)-agonists and corticosteroids		EUROPEAN RESPIRATORY JOURNAL	asthma; budesonide; fluticasone propionate; formoterol; salmeterol	AIRWAY SMOOTH-MUSCLE; LUNG MAST-CELLS; SALMETEROL/FLUTICASONE PROPIONATE COMBINATION; NK2 RECEPTOR EXPRESSION; DOWN-REGULATION; IN-VIVO; MU-G; GLUCOCORTICOID RECEPTOR; ADENOSINE-MONOPHOSPHATE; MICROVASCULAR LEAKAGE	The addition of an inhaled long-acting beta(2)-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients and two fixed combination inhalers (salmeterol/fluticasone and formoterol/budesonide) are increasingly used as a convenient controller in patients with persistent asthma. There is a strong scientific rationale for the combination of these two drug classes. ICS suppress the chronic inflammation of asthma and reduce airway hyperresponsiveness and this is achieved at low doses in most patients. LABA act on different aspects of the pathophysiology of asthma. In addition to their bronchodilator action, LABA also inhibit mast cell mediator release, plasma exudation and may reduce sensory nerve activation. Thus these two classes of drug address complementary aspects of the pathophysiology of asthma that neither drug class is able to achieve alone. There are several positive interactions between LABA and ICS. Corticosteroids increase the expression of beta(2)-receptors by increasing gene transcription. Experimentally this protects against the loss of beta(2)-receptors in response to long-term exposure to beta(2)-agonists. While this is unlikely to be important in bronchodilator responses to beta(2)-agonists, in view of the large beta-receptor reserve, it is probably important in preventing loss of beta-agonist effects on the nonbronchodilator actions of LABA discussed earlier. beta(2)-Agonists may potentiate the molecular mechanism of corticosteroid actions, with increased nuclear localization of glucocorticoid receptors and additive or sometimes synergistic suppression of inflammatory mediator release. Thus LABA and ICS may optimize each others beneficial actions in the airways, but the low systemic effects of these drugs do not result in any increase in adverse effects. Long-acting beta(2)-agonists corticosteroid inhaler therapy is therefore a logical advance and results in effective control of asthma in the majority of patients without significant adverse effects. This simplified approach to long-term asthma therapy has a strong scientific rationale.	106	263	2002	10	10.1183/09031936.02.00283202	Respiratory System
Do indoor pollutants and thermal conditions in schools influence student performance? A critical review of the literature. To assess whether school environments can adversely affect academic performance, we review scientific evidence relating indoor pollutants and thermal conditions, in schools or other indoor environments, to human performance or attendance. We critically review evidence for direct associations between these aspects of indoor environmental quality (IEQ) and performance or attendance. Secondarily, we summarize, without critique, evidence on indirect connections potentially linking IEQ to performance or attendance. Regarding direct associations, little strongly designed research was available. Persuasive evidence links higher indoor concentrations of NO2 to reduced school attendance, and suggestive evidence links low ventilation rates to reduced performance. Regarding indirect associations, many studies link indoor dampness and microbiologic pollutants (primarily in homes) to asthma exacerbations and respiratory infections, which in turn have been related to reduced performance and attendance. Also, much evidence links poor IEQ (e.g. low ventilation rate, excess moisture, or formaldehyde) with adverse health effects in children and adults and documents dampness problems and inadequate ventilation as common in schools. Overall, evidence suggests that poor IEQ in schools is common and adversely influences the performance and attendance of students, primarily through health effects from indoor pollutants. Evidence is available to justify (i) immediate actions to assess and improve IEQ in schools and (ii) focused research to guide IEQ improvements in schools.. indoor environment| indoor air quality| performance| schools| education| children|sick building syndrome| perceived air-quality| volatile organic-compounds| syndrome sbs symptoms| moderate heat-stress| day-care-centers| office workers| allergic sensitization| respiratory symptoms| young-children.	JAN-2005	indoor environment| indoor air quality| performance| schools| education| children|sick building syndrome| perceived air-quality| volatile organic-compounds| syndrome sbs symptoms| moderate heat-stress| day-care-centers| office workers| allergic sensitization| respiratory symptoms| young-children	Mendell, MJ; Heath, GA	Do indoor pollutants and thermal conditions in schools influence student performance? A critical review of the literature		INDOOR AIR	indoor environment; indoor air quality; performance; schools; education; children	SICK BUILDING SYNDROME; PERCEIVED AIR-QUALITY; VOLATILE ORGANIC-COMPOUNDS; SYNDROME SBS SYMPTOMS; MODERATE HEAT-STRESS; DAY-CARE-CENTERS; OFFICE WORKERS; ALLERGIC SENSITIZATION; RESPIRATORY SYMPTOMS; YOUNG-CHILDREN	To assess whether school environments can adversely affect academic performance, we review scientific evidence relating indoor pollutants and thermal conditions, in schools or other indoor environments, to human performance or attendance. We critically review evidence for direct associations between these aspects of indoor environmental quality (IEQ) and performance or attendance. Secondarily, we summarize, without critique, evidence on indirect connections potentially linking IEQ to performance or attendance. Regarding direct associations, little strongly designed research was available. Persuasive evidence links higher indoor concentrations of NO2 to reduced school attendance, and suggestive evidence links low ventilation rates to reduced performance. Regarding indirect associations, many studies link indoor dampness and microbiologic pollutants (primarily in homes) to asthma exacerbations and respiratory infections, which in turn have been related to reduced performance and attendance. Also, much evidence links poor IEQ (e.g. low ventilation rate, excess moisture, or formaldehyde) with adverse health effects in children and adults and documents dampness problems and inadequate ventilation as common in schools. Overall, evidence suggests that poor IEQ in schools is common and adversely influences the performance and attendance of students, primarily through health effects from indoor pollutants. Evidence is available to justify (i) immediate actions to assess and improve IEQ in schools and (ii) focused research to guide IEQ improvements in schools.	183	262	2005	26	10.1111/j.1600-0668.2004.00320.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Oral tolerance in the absence of naturally occurring Tregs. Mucosal tolerance prevents pathological reactions against environmental and food antigens, and its failure results in exacerbated inflammation typical of allergies and asthma. One of the proposed mechanisms of oral tolerance is the induction of Tregs. Using a mouse model of hyper-IgE and asthma, we found that oral tolerance could be effectively induced in the absence of naturally occurring thymus-derived Tregs. Oral antigen administration prior to i.p. immunization prevented effector/memory Th2 cell development, germinal center formation, class switching to IgE, and lung inflammation. Oral exposure to antigen induced development of antigen-specific CD4(+)CD25(+)Foxp3(+)CD45RB(low) cells that were anergic and displayed suppressive activity in vivo and in vitro. Oral tolerance to the Th2 allergic response was in large part dependent on TGF-beta and independent of IL-10. Interestingly, Tregs were also induced by single i.p. immunization with antigen and adjuvant. However, unlike oral administration of antigen, which induced Tregs but not effector T cells, i.p. immunization led to the simultaneous induction of Tregs and effector Th2 cells displaying the same antigen specificity.. regulatory t-cells| transcription factor foxp3| receptor transgenic mice| growth-factor-beta| in-vivo expansion| tgf-beta| autoimmune encephalomyelitis| cutting edge| peripheral tolerance| airway inflammation.	JUL-2005	regulatory t-cells| transcription factor foxp3| receptor transgenic mice| growth-factor-beta| in-vivo expansion| tgf-beta| autoimmune encephalomyelitis| cutting edge| peripheral tolerance| airway inflammation	Mucida, D; Kutchukhidze, N; Erazo, A; Russo, M; Lafaille, JJ; de Lafaille, MAC	Oral tolerance in the absence of naturally occurring Tregs		JOURNAL OF CLINICAL INVESTIGATION		REGULATORY T-CELLS; TRANSCRIPTION FACTOR FOXP3; RECEPTOR TRANSGENIC MICE; GROWTH-FACTOR-BETA; IN-VIVO EXPANSION; TGF-BETA; AUTOIMMUNE ENCEPHALOMYELITIS; CUTTING EDGE; PERIPHERAL TOLERANCE; AIRWAY INFLAMMATION	Mucosal tolerance prevents pathological reactions against environmental and food antigens, and its failure results in exacerbated inflammation typical of allergies and asthma. One of the proposed mechanisms of oral tolerance is the induction of Tregs. Using a mouse model of hyper-IgE and asthma, we found that oral tolerance could be effectively induced in the absence of naturally occurring thymus-derived Tregs. Oral antigen administration prior to i.p. immunization prevented effector/memory Th2 cell development, germinal center formation, class switching to IgE, and lung inflammation. Oral exposure to antigen induced development of antigen-specific CD4(+)CD25(+)Foxp3(+)CD45RB(low) cells that were anergic and displayed suppressive activity in vivo and in vitro. Oral tolerance to the Th2 allergic response was in large part dependent on TGF-beta and independent of IL-10. Interestingly, Tregs were also induced by single i.p. immunization with antigen and adjuvant. However, unlike oral administration of antigen, which induced Tregs but not effector T cells, i.p. immunization led to the simultaneous induction of Tregs and effector Th2 cells displaying the same antigen specificity.	69	258	2005	11	10.1172/JCI24487	Research & Experimental Medicine
Physicians' decisions to override computerized drug alerts in primary care. Background: Although computerized physician order entry reduces medication errors among inpatients, little is known about the use of this system in primary care. Methods: We calculated the override rate among 3481 consecutive alerts generated at 5 adult primary care practices that use a common computerized physician order entry system for prescription writing. For detailed review, we selected a random sample of 67 alerts in which physicians did not prescribe an alerted medication and 122 alerts that resulted in a written prescription. We identified factors associated with the physicians' decisions to override a medication alert, and determined whether an adverse drug event (ADE) occurred. Results: Physicians overrode 91.2% of drug allergy and 89.4% of high-severity drug interaction alerts. In the multivariable analysis using the medical chart review sample (n=189), physicians were less likely to prescribe an alerted medication if the prescriber was a house officer (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08-0.84) and if the patient had many drug allergies (OR, 0.70; 95% CI, 0.53-0.93). They were more likely to override alerts for renewals compared with new prescriptions (OR, 17.74; 95% CI, 5.60-56.18). We found no ADEs in cases where physicians observed the alert and 3 ADEs among patients with alert overrides, a nonsignificant difference (P=.55). Physician reviewers judged that 36.5% of the alerts were inappropriate. Conclusions: Few physicians changed their prescription in response to a drug allergy or interaction alert, and there were few ADEs, suggesting that the threshold for alerting was set too low. Computerized physician order entry systems should suppress alerts for renewals of medication combinations that patients currently tolerate.. medication errors| controlled trial| ambulatory-care| order entry| reminders| system| record| events.	NOV 24-2003	medication errors| controlled trial| ambulatory-care| order entry| reminders| system| record| events	Weingart, SN; Toth, M; Sands, DZ; Aronson, MD; Davis, RB; Phillips, RS	Physicians' decisions to override computerized drug alerts in primary care		ARCHIVES OF INTERNAL MEDICINE		MEDICATION ERRORS; CONTROLLED TRIAL; AMBULATORY-CARE; ORDER ENTRY; REMINDERS; SYSTEM; RECORD; EVENTS	Background: Although computerized physician order entry reduces medication errors among inpatients, little is known about the use of this system in primary care. Methods: We calculated the override rate among 3481 consecutive alerts generated at 5 adult primary care practices that use a common computerized physician order entry system for prescription writing. For detailed review, we selected a random sample of 67 alerts in which physicians did not prescribe an alerted medication and 122 alerts that resulted in a written prescription. We identified factors associated with the physicians' decisions to override a medication alert, and determined whether an adverse drug event (ADE) occurred. Results: Physicians overrode 91.2% of drug allergy and 89.4% of high-severity drug interaction alerts. In the multivariable analysis using the medical chart review sample (n=189), physicians were less likely to prescribe an alerted medication if the prescriber was a house officer (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08-0.84) and if the patient had many drug allergies (OR, 0.70; 95% CI, 0.53-0.93). They were more likely to override alerts for renewals compared with new prescriptions (OR, 17.74; 95% CI, 5.60-56.18). We found no ADEs in cases where physicians observed the alert and 3 ADEs among patients with alert overrides, a nonsignificant difference (P=.55). Physician reviewers judged that 36.5% of the alerts were inappropriate. Conclusions: Few physicians changed their prescription in response to a drug allergy or interaction alert, and there were few ADEs, suggesting that the threshold for alerting was set too low. Computerized physician order entry systems should suppress alerts for renewals of medication combinations that patients currently tolerate.	21	258	2003	7	10.1001/archinte.163.21.2625	General & Internal Medicine
On the safety of Aspergillus niger - a review. Aspergillus niger is one of the most important microorganisms used in biotechnology. It has been in use already for many decades to produce extracellular (food) enzymes and citric acid. In fact, citric acid and many A. niger enzymes are considered GRAS by the United States Food and Drug Administration. In addition, A. niger is used for biotransformations and waste treatment. In the last two decades, A. niger has been developed as an important transformation host to over-express food enzymes. Being pre-dated by older names, the name A. niger has been conserved for economical and information retrieval reasons and there is a taxonomical consensus based on molecular data that the only other common species closely related to A. niger in the Aspergillus series Nigri is A. tubingensis. A. niger, like other filamentous fungi, should be treated carefully to avoid the formation of spore dust. However, compared with other filamentous fungi, it does not stand out as a particular problem concerning allergy or mycopathology. A few medical cases, e.g. lung infections, have been reported, but always in severely immunocompromised patients. In tropical areas, ear infections (otomycosis) do occur due to A. niger invasion of the outer ear canal but this may be caused by mechanical damage of the skin barrier. A. niger strains produce a series of secondary metabolites, but it is only ochratoxin A that can be regarded as a mycotoxin in the strict sense of the word. Only 3-10% of the strains examined for ochratoxin A production have tested positive under favourable conditions. New and unknown isolates should be checked for ochratoxin A production before they are developed as production organisms. It is concluded, with these restrictions, that A. niger is a safe production organism.. fragment-length-polymorphisms| green coffee beans| black aspergilli| ochratoxin-a| cutaneous aspergillosis| aflatoxin production| microbial esterases| biotechnology plant| stored cottonseed| molecular-cloning.	AUG-2002	fragment-length-polymorphisms| green coffee beans| black aspergilli| ochratoxin-a| cutaneous aspergillosis| aflatoxin production| microbial esterases| biotechnology plant| stored cottonseed| molecular-cloning	Schuster, E; Dunn-Coleman, N; Frisvad, JC; van Dijck, PWM	On the safety of Aspergillus niger - a review		APPLIED MICROBIOLOGY AND BIOTECHNOLOGY		FRAGMENT-LENGTH-POLYMORPHISMS; GREEN COFFEE BEANS; BLACK ASPERGILLI; OCHRATOXIN-A; CUTANEOUS ASPERGILLOSIS; AFLATOXIN PRODUCTION; MICROBIAL ESTERASES; BIOTECHNOLOGY PLANT; STORED COTTONSEED; MOLECULAR-CLONING	Aspergillus niger is one of the most important microorganisms used in biotechnology. It has been in use already for many decades to produce extracellular (food) enzymes and citric acid. In fact, citric acid and many A. niger enzymes are considered GRAS by the United States Food and Drug Administration. In addition, A. niger is used for biotransformations and waste treatment. In the last two decades, A. niger has been developed as an important transformation host to over-express food enzymes. Being pre-dated by older names, the name A. niger has been conserved for economical and information retrieval reasons and there is a taxonomical consensus based on molecular data that the only other common species closely related to A. niger in the Aspergillus series Nigri is A. tubingensis. A. niger, like other filamentous fungi, should be treated carefully to avoid the formation of spore dust. However, compared with other filamentous fungi, it does not stand out as a particular problem concerning allergy or mycopathology. A few medical cases, e.g. lung infections, have been reported, but always in severely immunocompromised patients. In tropical areas, ear infections (otomycosis) do occur due to A. niger invasion of the outer ear canal but this may be caused by mechanical damage of the skin barrier. A. niger strains produce a series of secondary metabolites, but it is only ochratoxin A that can be regarded as a mycotoxin in the strict sense of the word. Only 3-10% of the strains examined for ochratoxin A production have tested positive under favourable conditions. New and unknown isolates should be checked for ochratoxin A production before they are developed as production organisms. It is concluded, with these restrictions, that A. niger is a safe production organism.	130	257	2002	10	10.1007/s00253-002-1032-6	Biotechnology & Applied Microbiology
The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. CCR3 is a chemokine receptor initially thought specific to eosinophils but subsequently identified on TH2 cell subsets, basophils, mast cells, neural tissue, and some epithelia. Because of the prominent role of these cells in allergic disease, including asthma, we generated mice deficient in CCR3 to determine its contribution in a model of allergic airway disease. Here we show that CCR3 is important for the basal trafficking of eosinophils to the intestinal mucosa but not the lung. In contrast, CCR3 disruption significantly curtails eosinophil recruitment to the lung after allergen challenge, with the majority of the eosinophils being arrested in the subendothelial space. Further, a role for CCR3 in mast cell homing has been identified; after sensitization and allergen challenge, we find increased numbers of intraepithelial mast cells in the trachea of knockout mice. Physiologically, we find that the net result of these complex cell fates after sensitization and allergen challenge is a paradoxical increase in airway responsiveness to cholinergic stimulation. These data underscore a more complex role for CCR3 in allergic disease than was anticipated.. guinea-pig model| asthma model| chemokine eotaxin| in-vivo| expression| mice| lung| interleukin-5| recruitment| activation.	FEB 5-2002	guinea-pig model| asthma model| chemokine eotaxin| in-vivo| expression| mice| lung| interleukin-5| recruitment| activation	Humbles, AA; Lu, B; Friend, DS; Okinaga, S; Lora, J; Al-garawi, A; Martin, TR; Gerard, NP; Gerard, C	The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA		GUINEA-PIG MODEL; ASTHMA MODEL; CHEMOKINE EOTAXIN; IN-VIVO; EXPRESSION; MICE; LUNG; INTERLEUKIN-5; RECRUITMENT; ACTIVATION	CCR3 is a chemokine receptor initially thought specific to eosinophils but subsequently identified on TH2 cell subsets, basophils, mast cells, neural tissue, and some epithelia. Because of the prominent role of these cells in allergic disease, including asthma, we generated mice deficient in CCR3 to determine its contribution in a model of allergic airway disease. Here we show that CCR3 is important for the basal trafficking of eosinophils to the intestinal mucosa but not the lung. In contrast, CCR3 disruption significantly curtails eosinophil recruitment to the lung after allergen challenge, with the majority of the eosinophils being arrested in the subendothelial space. Further, a role for CCR3 in mast cell homing has been identified; after sensitization and allergen challenge, we find increased numbers of intraepithelial mast cells in the trachea of knockout mice. Physiologically, we find that the net result of these complex cell fates after sensitization and allergen challenge is a paradoxical increase in airway responsiveness to cholinergic stimulation. These data underscore a more complex role for CCR3 in allergic disease than was anticipated.	41	257	2002	6	10.1073/pnas.261462598	Science & Technology - Other Topics
Aerobiology and the global transport of desert dust. Desert winds aerosolize several billion tons of soil-derived dust each year, including concentrated seasonal pulses from Africa and Asia. These transoceanic and transcontinental dust events inject a large pulse of microorganisms and pollen into the atmosphere and could therefore have a role in transporting pathogens or expanding the biogeographical range of some organisms by facilitating long-distance dispersal events. As we discuss here, whether such dispersal events are occurring is only now beginning to be investigated. Huge dust events create an atmospheric bridge over land and sea, and the microbiota contained within them could impact downwind ecosystems. Such dispersal is of interest because of the possible health effects of allergens and pathogens that might be carried with the dust.. ambient fungal spores| aerial dispersal| airborne spread| mouth-disease| african dust| coral-reefs| asian dust| soil dust| bacteria| diversity.	NOV-2006	ambient fungal spores| aerial dispersal| airborne spread| mouth-disease| african dust| coral-reefs| asian dust| soil dust| bacteria| diversity	Kellogg, CA; Griffin, DW	Aerobiology and the global transport of desert dust		TRENDS IN ECOLOGY & EVOLUTION		AMBIENT FUNGAL SPORES; AERIAL DISPERSAL; AIRBORNE SPREAD; MOUTH-DISEASE; AFRICAN DUST; CORAL-REEFS; ASIAN DUST; SOIL DUST; BACTERIA; DIVERSITY	Desert winds aerosolize several billion tons of soil-derived dust each year, including concentrated seasonal pulses from Africa and Asia. These transoceanic and transcontinental dust events inject a large pulse of microorganisms and pollen into the atmosphere and could therefore have a role in transporting pathogens or expanding the biogeographical range of some organisms by facilitating long-distance dispersal events. As we discuss here, whether such dispersal events are occurring is only now beginning to be investigated. Huge dust events create an atmospheric bridge over land and sea, and the microbiota contained within them could impact downwind ecosystems. Such dispersal is of interest because of the possible health effects of allergens and pathogens that might be carried with the dust.	61	256	2006	7	10.1016/j.tree.2006.07.004	Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity
The relationship between air pollution from heavy traffic and allergic sensitization, bronchial hyperresponsiveness, and respiratory symptoms in Dutch schoolchildren. Studies have suggested that children living close to busy roads may have impaired respiratory health. This study was designed to test the hypothesis that exposure to exhaust from heavy traffic in particular is related to childhood respiratory health. Children attending 24 schools located within 400 in from busy motorways were investigated. The motorways carried between 5,190 and 22,326 trucks per weekday and between 30,399 and 155,656 cars per day. Locations were chosen so that the correlation between truck and car traffic counts was low. Air pollution measurements were performed at the schools for I year. Respiratory symptoms were collected by parent-completed questionnaire. Sensitization to common allergens was measured by serum immunoglobulin E and skin prick tests. Bronchial hyperresponsiveness (BHR) was measured with a hypertonic saline challenge. Respiratory symptoms were increased near motorways with high truck but not high car traffic counts. They were also related to air pollutants that increased near motorways with high truck traffic counts. Lung function and BHR were not related to pollution. Sensitization to pollen increased in relation to truck but not car traffic counts. The relation between symptoms and measures of exposure to (truck) traffic-related air pollution were almost entirely restricted to children with BHR and/or sensitization to common allergens, indicating that these are a sensitive subgroup among all children for these effects.. air pollution| allergy| bronchial hyperresponsiveness| children| diesel| lung function| respiratory symptoms|diesel exhaust particles| lung-function| adjuvant activity| childhood asthma| expiratory flow| children| exposure| health| road| atopy.	SEP-2003	air pollution| allergy| bronchial hyperresponsiveness| children| diesel| lung function| respiratory symptoms|diesel exhaust particles| lung-function| adjuvant activity| childhood asthma| expiratory flow| children| exposure| health| road| atopy	Janssen, NAH; Brunekreef, B; van Vliet, P; Aarts, F; Meliefste, K; Harssema, H; Fischer, P	The relationship between air pollution from heavy traffic and allergic sensitization, bronchial hyperresponsiveness, and respiratory symptoms in Dutch schoolchildren		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; allergy; bronchial hyperresponsiveness; children; diesel; lung function; respiratory symptoms	DIESEL EXHAUST PARTICLES; LUNG-FUNCTION; ADJUVANT ACTIVITY; CHILDHOOD ASTHMA; EXPIRATORY FLOW; CHILDREN; EXPOSURE; HEALTH; ROAD; ATOPY	Studies have suggested that children living close to busy roads may have impaired respiratory health. This study was designed to test the hypothesis that exposure to exhaust from heavy traffic in particular is related to childhood respiratory health. Children attending 24 schools located within 400 in from busy motorways were investigated. The motorways carried between 5,190 and 22,326 trucks per weekday and between 30,399 and 155,656 cars per day. Locations were chosen so that the correlation between truck and car traffic counts was low. Air pollution measurements were performed at the schools for I year. Respiratory symptoms were collected by parent-completed questionnaire. Sensitization to common allergens was measured by serum immunoglobulin E and skin prick tests. Bronchial hyperresponsiveness (BHR) was measured with a hypertonic saline challenge. Respiratory symptoms were increased near motorways with high truck but not high car traffic counts. They were also related to air pollutants that increased near motorways with high truck traffic counts. Lung function and BHR were not related to pollution. Sensitization to pollen increased in relation to truck but not car traffic counts. The relation between symptoms and measures of exposure to (truck) traffic-related air pollution were almost entirely restricted to children with BHR and/or sensitization to common allergens, indicating that these are a sensitive subgroup among all children for these effects.	42	256	2003	7	10.1289/ehp.6243	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
"Bronchodilator reversibility testing in chronic obstructive pulmonary disease. Background: A limited or absent bronchodilator response is used to classify chronic obstructive pulmonary disease (COPD) and can determine the treatment offered. The reliability of the recommended response criteria and their relationship to disease progression has not been established. Methods: 660 patients meeting European Respiratory Society (ERS) diagnostic criteria for irreversible COPD were studied. Spirometric parameters were measured on three occasions before and after salbutamol and ipratropium bromide sequentially or in combination over 2 months. Responses were classified using the American Thoracic Society/GOLD (ATS) and ERS criteria. Patients were followed for 3 years with post-bronchodilator FEV1 and exacerbation history recorded 3 monthly and health status 6 monthly. Results: FEV1 increased significantly with each bronchodilator, a response that was normally distributed. Mean post-bronchodilator FEV1 was reproducible between visits (intraclass correlation 0.93). The absolute change in FEV1 was independent of the pre-bronchodilator value but the percentage change correlated with pre-bronchodilator FEV1 (r=-0.44; p<0.0001). Using ATS criteria, 52.1% of patients changed responder status between visits compared with 38.2% using ERS criteria. Smoking status, atopy, and withdrawing inhaled corticosteroids were unrelated to bronchodilator response, as was the rate of decline in FEV1, decline in health status, and exacerbation rate. Conclusion: In moderate to severe COPD bronchodilator responsiveness is a continuous variable. Classifying patients as ""responders"" and ""non-responders"" can be misleading and does not predict disease progression.. air-flow obstruction| corticosteroid trials| copd| management| smoking| asthma| fev1."	AUG-2003	air-flow obstruction| corticosteroid trials| copd| management| smoking| asthma| fev1	Calverley, PMA; Burge, PS; Spencer, S; Anderson, JA; Jones, PW	Bronchodilator reversibility testing in chronic obstructive pulmonary disease		THORAX		AIR-FLOW OBSTRUCTION; CORTICOSTEROID TRIALS; COPD; MANAGEMENT; SMOKING; ASTHMA; FEV1	"Background: A limited or absent bronchodilator response is used to classify chronic obstructive pulmonary disease (COPD) and can determine the treatment offered. The reliability of the recommended response criteria and their relationship to disease progression has not been established. Methods: 660 patients meeting European Respiratory Society (ERS) diagnostic criteria for irreversible COPD were studied. Spirometric parameters were measured on three occasions before and after salbutamol and ipratropium bromide sequentially or in combination over 2 months. Responses were classified using the American Thoracic Society/GOLD (ATS) and ERS criteria. Patients were followed for 3 years with post-bronchodilator FEV1 and exacerbation history recorded 3 monthly and health status 6 monthly. Results: FEV1 increased significantly with each bronchodilator, a response that was normally distributed. Mean post-bronchodilator FEV1 was reproducible between visits (intraclass correlation 0.93). The absolute change in FEV1 was independent of the pre-bronchodilator value but the percentage change correlated with pre-bronchodilator FEV1 (r=-0.44; p<0.0001). Using ATS criteria, 52.1% of patients changed responder status between visits compared with 38.2% using ERS criteria. Smoking status, atopy, and withdrawing inhaled corticosteroids were unrelated to bronchodilator response, as was the rate of decline in FEV1, decline in health status, and exacerbation rate. Conclusion: In moderate to severe COPD bronchodilator responsiveness is a continuous variable. Classifying patients as ""responders"" and ""non-responders"" can be misleading and does not predict disease progression."	29	256	2003	6	10.1136/thorax.58.8.659	Respiratory System
Racial/ethnic variation in asthma status and management practices among children in managed medicaid. Objective. Racial/ethnic disparities in hospitalization rates among children with asthma have been documented but are not well-understood. Medicaid programs, which serve many minority children, have markedly increased their use of managed care in recent years. It is unknown whether racial/ethnic disparities in health care use or other processes of care exist in managed Medicaid populations. This study of Medicaid-insured children with asthma in 5 managed care organizations aimed to 1) compare parent-reported health status and asthma care processes among black, Latino, and white children and 2) test the hypothesis that racial/ ethnic variations in processes of asthma care exist after adjusting for socioeconomic status and asthma status. Methods. This cross-sectional study collected data via telephone interviews with parents and computerized records for Medicaid-insured children with asthma in 5 managed care organizations in California, Washington, and Massachusetts. The American Academy of Pediatrics (AAP) Children's Health Survey for Asthma was used to measure parent-reported asthma status. We used multivariate models to evaluate associations between race/ethnicity and asthma status while controlling for other sociodemographic variables. We evaluated racial/ ethnic variations in selected processes of asthma care while controlling for other demographic variables and asthma status. Results. The response rate was 63%. Of the 1658 children in the respondent group, 38% were black, 19% were Latino, and 31% were white. Black children had worse asthma status than white children on the basis of the AAP asthma physical and emotional health scores, symptom-days, and school days missed in the past 2 weeks. Latino children had equivalent AAP scores but missed more school days than white children. On the basis of the AAP asthma physical health score, the black-white disparity persisted after adjusting for other sociodemographic variables. After adjusting for sociodemographic variables and asthma status, black and Latino children were less likely to be using inhaled antiinflammatory medication than white children (relative risk for blacks: 0.69; relative risk for Latinos: 0.58). They were more likely to have home nebulizers. Other processes of asthma care, including ratings of providers and asthma care, use of written management plans, use of preventive visits and specialists, and having no pets or smokers at home, were equal or better for minority children compared with white children. Conclusions. Black and Latino children had worse asthma status and less use of preventive asthma medications than white children within the same managed Medicaid populations. Most other processes of asthma care seemed to be equal or better for minorities in the populations that we studied. Increasing the use of preventive medications is a natural focus for reducing racial disparities in asthma.. asthma| race| race/ethnicity| health status| quality of care| processes of care| managed care|health maintenance organization| patient-physician relationship| african-american children| inner-city children| racial-differences| ethnic-differences| childhood asthma| united-states| renal-transplantation| cultural competence.	MAY-2002	asthma| race| race/ethnicity| health status| quality of care| processes of care| managed care|health maintenance organization| patient-physician relationship| african-american children| inner-city children| racial-differences| ethnic-differences| childhood asthma| united-states| renal-transplantation| cultural competence	Lieu, TA; Lozano, P; Finkelstein, JA; Chi, FW; Jensvold, NG; Capra, AM; Quesenberry, CP; Selby, JV; Farber, HJ	Racial/ethnic variation in asthma status and management practices among children in managed medicaid		PEDIATRICS	asthma; race; race/ethnicity; health status; quality of care; processes of care; managed care	HEALTH MAINTENANCE ORGANIZATION; PATIENT-PHYSICIAN RELATIONSHIP; AFRICAN-AMERICAN CHILDREN; INNER-CITY CHILDREN; RACIAL-DIFFERENCES; ETHNIC-DIFFERENCES; CHILDHOOD ASTHMA; UNITED-STATES; RENAL-TRANSPLANTATION; CULTURAL COMPETENCE	Objective. Racial/ethnic disparities in hospitalization rates among children with asthma have been documented but are not well-understood. Medicaid programs, which serve many minority children, have markedly increased their use of managed care in recent years. It is unknown whether racial/ethnic disparities in health care use or other processes of care exist in managed Medicaid populations. This study of Medicaid-insured children with asthma in 5 managed care organizations aimed to 1) compare parent-reported health status and asthma care processes among black, Latino, and white children and 2) test the hypothesis that racial/ ethnic variations in processes of asthma care exist after adjusting for socioeconomic status and asthma status. Methods. This cross-sectional study collected data via telephone interviews with parents and computerized records for Medicaid-insured children with asthma in 5 managed care organizations in California, Washington, and Massachusetts. The American Academy of Pediatrics (AAP) Children's Health Survey for Asthma was used to measure parent-reported asthma status. We used multivariate models to evaluate associations between race/ethnicity and asthma status while controlling for other sociodemographic variables. We evaluated racial/ ethnic variations in selected processes of asthma care while controlling for other demographic variables and asthma status. Results. The response rate was 63%. Of the 1658 children in the respondent group, 38% were black, 19% were Latino, and 31% were white. Black children had worse asthma status than white children on the basis of the AAP asthma physical and emotional health scores, symptom-days, and school days missed in the past 2 weeks. Latino children had equivalent AAP scores but missed more school days than white children. On the basis of the AAP asthma physical health score, the black-white disparity persisted after adjusting for other sociodemographic variables. After adjusting for sociodemographic variables and asthma status, black and Latino children were less likely to be using inhaled antiinflammatory medication than white children (relative risk for blacks: 0.69; relative risk for Latinos: 0.58). They were more likely to have home nebulizers. Other processes of asthma care, including ratings of providers and asthma care, use of written management plans, use of preventive visits and specialists, and having no pets or smokers at home, were equal or better for minority children compared with white children. Conclusions. Black and Latino children had worse asthma status and less use of preventive asthma medications than white children within the same managed Medicaid populations. Most other processes of asthma care seemed to be equal or better for minorities in the populations that we studied. Increasing the use of preventive medications is a natural focus for reducing racial disparities in asthma.	81	256	2002	9	10.1542/peds.109.5.857	Pediatrics
CD4(+) CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. The role of natural CD4(+)CD25(+) regulatory T ( T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness ( AHR). In C3H mice, anti-CD25-mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis ( AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 ( Th2) cytokine production. In similarly T reg cell-depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells ( DCs) in T reg cell-depleted C3H mice. T reg cell-depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell-depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4(+)CD25(+) T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.. induced airway hyperresponsiveness| tryptophan catabolism| hygiene hypothesis| immune-responses| allergic disease| regulatory cells| cutting edge| antigen| suppression| induction.	DEC 5-2005	induced airway hyperresponsiveness| tryptophan catabolism| hygiene hypothesis| immune-responses| allergic disease| regulatory cells| cutting edge| antigen| suppression| induction	Lewkowich, IP; Herman, NS; Schleifer, KW; Dance, MP; Chen, BL; Dienger, KM; Sproles, AA; Shah, JS; Kohl, J; Belkaid, Y; Wills-Karp, M	CD4(+) CD25(+) T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function		JOURNAL OF EXPERIMENTAL MEDICINE		INDUCED AIRWAY HYPERRESPONSIVENESS; TRYPTOPHAN CATABOLISM; HYGIENE HYPOTHESIS; IMMUNE-RESPONSES; ALLERGIC DISEASE; REGULATORY CELLS; CUTTING EDGE; ANTIGEN; SUPPRESSION; INDUCTION	The role of natural CD4(+)CD25(+) regulatory T ( T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness ( AHR). In C3H mice, anti-CD25-mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis ( AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 ( Th2) cytokine production. In similarly T reg cell-depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells ( DCs) in T reg cell-depleted C3H mice. T reg cell-depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell-depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4(+)CD25(+) T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.	40	255	2005	13	10.1084/jem.20051506	Immunology; Research & Experimental Medicine
"Case-crossover analyses of air pollution exposure data - Referent selection strategies and their implications for bias. The case-crossover design has been widely used to study the association between short-term air pollution exposure and the risk of an acute adverse health event. The design uses cases only; for each individual case, exposure just before the event is compared with exposure at other control (or ""referent"") times. Time-invariant confounders are controlled by making within-subject comparisons. Even more important in the air pollution setting is that time-varying confounders can also be controlled by design by matching referents to the index time. The referent selection strategy is important for reasons in addition to control of confounding. The case-crossover design makes the implicit assumption that there is no trend in exposure across the referent times. In addition, the statistical method that is used-conditional logistic regression-is unbiased only with certain referent strategies. We review here the case-crossover literature in the air pollution context, focusing on key issues regarding referent selection. We conclude with a set of recommendations for choosing a referent strategy with air pollution exposure data. Specifically, we advocate the time-stratified approach to referent selection because it ensures unbiased conditional logistic regression estimates, avoids bias resulting from time trend in the exposure series, and can be tailored to match on specific time-varying confounders.. bidirectional case-crossover| primary cardiac-arrest| daily mortality| particulate matter| time-series| asthma hospitalization| myocardial-infarction| risk| designs| taiwan."	NOV-2005	bidirectional case-crossover| primary cardiac-arrest| daily mortality| particulate matter| time-series| asthma hospitalization| myocardial-infarction| risk| designs| taiwan	Janes, H; Sheppard, L; Lumley, T	Case-crossover analyses of air pollution exposure data - Referent selection strategies and their implications for bias		EPIDEMIOLOGY		BIDIRECTIONAL CASE-CROSSOVER; PRIMARY CARDIAC-ARREST; DAILY MORTALITY; PARTICULATE MATTER; TIME-SERIES; ASTHMA HOSPITALIZATION; MYOCARDIAL-INFARCTION; RISK; DESIGNS; TAIWAN	"The case-crossover design has been widely used to study the association between short-term air pollution exposure and the risk of an acute adverse health event. The design uses cases only; for each individual case, exposure just before the event is compared with exposure at other control (or ""referent"") times. Time-invariant confounders are controlled by making within-subject comparisons. Even more important in the air pollution setting is that time-varying confounders can also be controlled by design by matching referents to the index time. The referent selection strategy is important for reasons in addition to control of confounding. The case-crossover design makes the implicit assumption that there is no trend in exposure across the referent times. In addition, the statistical method that is used-conditional logistic regression-is unbiased only with certain referent strategies. We review here the case-crossover literature in the air pollution context, focusing on key issues regarding referent selection. We conclude with a set of recommendations for choosing a referent strategy with air pollution exposure data. Specifically, we advocate the time-stratified approach to referent selection because it ensures unbiased conditional logistic regression estimates, avoids bias resulting from time trend in the exposure series, and can be tailored to match on specific time-varying confounders."	44	255	2005	10	10.1097/01.edu.0000181315.18836.9d	Public, Environmental & Occupational Health
The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?. Allergic atopic disorders, such as rhinitis, asthma, and atopic dermatitis, are the result of a systemic inflammatory reaction triggered by type 2 T helper (Th2) cell-mediated immune responses against 'innocuous' antigens (allergens) of complex genetic and environmental origin. A number of epidemiological studies have suggested that the increase in the prevalence of allergic disorders that has occurred over the past few decades is attributable to a reduced microbial burden during childhood, as a consequence of Westernized lifestyle (the 'hygiene hypothesis'). However, the mechanisms by which the reduced exposure of children to pathogenic and nonpathogenic microbes results in enhanced responses of Th2 cells are still controversial. The initial interpretation proposed a missing immune deviation of allergen-specific responses from a Th2 to a type 1 Th (Th1) profile, as a result of the reduced production of interleukin-12 and interferons by natural immunity cells which are stimulated by bacterial products via their Toll-like receptors. More recently, the role of reduced activity of T regulatory cells has been emphasized. The epidemiological findings and the experimental evidence available so far suggest that both mechanisms may be involved. A better understanding of this question is important not only from a theoretical point of view, but also because of its therapeutic implications.. hygiene hypothesis| immune deviation| immune suppression| th1/th2 cells| treg cells|regulatory t-cells| induced airway hyperresponsiveness| grass-pollen immunotherapy| toll-like receptor-2| multiple-sclerosis| ifn-gamma| interferon-gamma| dendritic cells| gene-transfer| helper-cells.	JUL-2004	hygiene hypothesis| immune deviation| immune suppression| th1/th2 cells| treg cells|regulatory t-cells| induced airway hyperresponsiveness| grass-pollen immunotherapy| toll-like receptor-2| multiple-sclerosis| ifn-gamma| interferon-gamma| dendritic cells| gene-transfer| helper-cells	Romagnani, S	The increased prevalence of allergy and the hygiene hypothesis: missing immune deviation, reduced immune suppression, or both?		IMMUNOLOGY	hygiene hypothesis; immune deviation; immune suppression; Th1/Th2 cells; Treg cells	REGULATORY T-CELLS; INDUCED AIRWAY HYPERRESPONSIVENESS; GRASS-POLLEN IMMUNOTHERAPY; TOLL-LIKE RECEPTOR-2; MULTIPLE-SCLEROSIS; IFN-GAMMA; INTERFERON-GAMMA; DENDRITIC CELLS; GENE-TRANSFER; HELPER-CELLS	Allergic atopic disorders, such as rhinitis, asthma, and atopic dermatitis, are the result of a systemic inflammatory reaction triggered by type 2 T helper (Th2) cell-mediated immune responses against 'innocuous' antigens (allergens) of complex genetic and environmental origin. A number of epidemiological studies have suggested that the increase in the prevalence of allergic disorders that has occurred over the past few decades is attributable to a reduced microbial burden during childhood, as a consequence of Westernized lifestyle (the 'hygiene hypothesis'). However, the mechanisms by which the reduced exposure of children to pathogenic and nonpathogenic microbes results in enhanced responses of Th2 cells are still controversial. The initial interpretation proposed a missing immune deviation of allergen-specific responses from a Th2 to a type 1 Th (Th1) profile, as a result of the reduced production of interleukin-12 and interferons by natural immunity cells which are stimulated by bacterial products via their Toll-like receptors. More recently, the role of reduced activity of T regulatory cells has been emphasized. The epidemiological findings and the experimental evidence available so far suggest that both mechanisms may be involved. A better understanding of this question is important not only from a theoretical point of view, but also because of its therapeutic implications.	110	255	2004	12	10.1111/j.1365-2567.2004.01925.x	Immunology
Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection and Immunopathology. Stress is known to suppress immune function and increase susceptibility to infections and cancer. Paradoxically, stress is also known to exacerbate asthma, and allergic, autoimmune and inflammatory diseases, although such diseases should be ameliorated by immunosuppression. Moreover, the short-term fight-or-flight stress response is one of nature's fundamental defense mechanisms that enables the cardiovascular and musculoskeletal systems to promote survival, and it is unlikely that this response would suppress immune function at a time when it is most required for survival (e. g. in response to wounding and infection by a predator or aggressor). These observations suggest that stress may suppress immune function under some conditions while enhancing it under others. The effects of stress are likely to be beneficial or harmful depending on the type (immunoprotective, immunoregulatory/inhibitory, or immunopathological) of immune response that is affected. Studies have shown that several critical factors influence the direction (enhancing vs. suppressive) of the effects of stress or stress hormones on immune function: (1) Duration (acute vs. chronic) of stress: Acute or short-term stress experienced at the time of immune activation can enhance innate and adaptive immune responses. Chronic or long-term stress can suppress immunity by decreasing immune cell numbers and function and/or increasing active immunosuppressive mechanisms (e. g. regulatory T cells). Chronic stress can also dysregulate immune function by promoting proinflammatory and type-2 cytokine-driven responses. (2) Effects of stress on leukocyte distribution: Compartments that are enriched with immune cells during acute stress show immunoenhancement, while those that are depleted of leukocytes, show immunosuppression. (3) The differential effects of physiologic versus pharmacologic concentrations of glucocorticoids, and the differential effects of endogenous versus synthetic glucocorticoids: Endogenous hormones in physiological concentrations can have immunoenhancing effects. Endogenous hormones at pharmacologic concentrations, and synthetic hormones, are immunosuppressive. (4) The timing of stressor or stress hormone exposure relative to the time of activation and time course of the immune response: Immunoenhancement is observed when acute stress is experienced at early stages of immune activation, while immunosuppression may be observed at late stages of the immune response. We propose that it is important to study and, if possible, to clinically harness the immunoenhancing effects of the acute stress response, that evolution has finely sculpted as a survival mechanism, just as we study its maladaptive ramifications (chronic stress) that evolution has yet to resolve. In view of the ubiquitous nature of stress and its significant effects on immunoprotection as well as immunopathology, it is important to further elucidate the mechanisms mediating stress-immune interactions and to meaningfully translate findings from bench to bedside. Copyright (C) 2009 S. Karger AG, Basel. acute stress-induced enhancement| fight-or-flight stress| immune cell distribution| immune function, effects of stress| immune function, enhancing vs. suppressive effects| immunoprotection vs. immunopathology| innate/primary immune responses| leukocyte trafficking| adaptive/secondary immune responses|cell-mediated-immunity| peripheral-blood lymphocytes| experimental allergic encephalomyelitis| corticotropin-releasing hormone| acute psychological stress| pituitary-adrenal axis| acute-phase response| induced enhancement| glucocorticoid hormones| lewis rats.	2009	acute stress-induced enhancement| fight-or-flight stress| immune cell distribution| immune function, effects of stress| immune function, enhancing vs. suppressive effects| immunoprotection vs. immunopathology| innate/primary immune responses| leukocyte trafficking| adaptive/secondary immune responses|cell-mediated-immunity| peripheral-blood lymphocytes| experimental allergic encephalomyelitis| corticotropin-releasing hormone| acute psychological stress| pituitary-adrenal axis| acute-phase response| induced enhancement| glucocorticoid hormones| lewis rats	Dhabhar, FS	Enhancing versus Suppressive Effects of Stress on Immune Function: Implications for Immunoprotection and Immunopathology		NEUROIMMUNOMODULATION	Acute stress-induced enhancement; Fight-or-flight stress; Immune cell distribution; Immune function, effects of stress; Immune function, enhancing vs. suppressive effects; Immunoprotection vs. immunopathology; Innate/primary immune responses; Leukocyte trafficking; Adaptive/secondary immune responses	CELL-MEDIATED-IMMUNITY; PERIPHERAL-BLOOD LYMPHOCYTES; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CORTICOTROPIN-RELEASING HORMONE; ACUTE PSYCHOLOGICAL STRESS; PITUITARY-ADRENAL AXIS; ACUTE-PHASE RESPONSE; INDUCED ENHANCEMENT; GLUCOCORTICOID HORMONES; LEWIS RATS	Stress is known to suppress immune function and increase susceptibility to infections and cancer. Paradoxically, stress is also known to exacerbate asthma, and allergic, autoimmune and inflammatory diseases, although such diseases should be ameliorated by immunosuppression. Moreover, the short-term fight-or-flight stress response is one of nature's fundamental defense mechanisms that enables the cardiovascular and musculoskeletal systems to promote survival, and it is unlikely that this response would suppress immune function at a time when it is most required for survival (e. g. in response to wounding and infection by a predator or aggressor). These observations suggest that stress may suppress immune function under some conditions while enhancing it under others. The effects of stress are likely to be beneficial or harmful depending on the type (immunoprotective, immunoregulatory/inhibitory, or immunopathological) of immune response that is affected. Studies have shown that several critical factors influence the direction (enhancing vs. suppressive) of the effects of stress or stress hormones on immune function: (1) Duration (acute vs. chronic) of stress: Acute or short-term stress experienced at the time of immune activation can enhance innate and adaptive immune responses. Chronic or long-term stress can suppress immunity by decreasing immune cell numbers and function and/or increasing active immunosuppressive mechanisms (e. g. regulatory T cells). Chronic stress can also dysregulate immune function by promoting proinflammatory and type-2 cytokine-driven responses. (2) Effects of stress on leukocyte distribution: Compartments that are enriched with immune cells during acute stress show immunoenhancement, while those that are depleted of leukocytes, show immunosuppression. (3) The differential effects of physiologic versus pharmacologic concentrations of glucocorticoids, and the differential effects of endogenous versus synthetic glucocorticoids: Endogenous hormones in physiological concentrations can have immunoenhancing effects. Endogenous hormones at pharmacologic concentrations, and synthetic hormones, are immunosuppressive. (4) The timing of stressor or stress hormone exposure relative to the time of activation and time course of the immune response: Immunoenhancement is observed when acute stress is experienced at early stages of immune activation, while immunosuppression may be observed at late stages of the immune response. We propose that it is important to study and, if possible, to clinically harness the immunoenhancing effects of the acute stress response, that evolution has finely sculpted as a survival mechanism, just as we study its maladaptive ramifications (chronic stress) that evolution has yet to resolve. In view of the ubiquitous nature of stress and its significant effects on immunoprotection as well as immunopathology, it is important to further elucidate the mechanisms mediating stress-immune interactions and to meaningfully translate findings from bench to bedside. Copyright (C) 2009 S. Karger AG, Basel	112	254	2009	18	10.1159/000216188	Endocrinology & Metabolism; Immunology; Neurosciences & Neurology
Health effects of diesel exhaust emissions. Epidemiological studies have demonstrated an association between different levels of air pollution and various health outcomes including mortality, exacerbation of asthma, chronic bronchitis, respiratory tract infections, ischaemic heart disease and stroke. Of the motor vehicle generated air pollutants, diesel exhaust particles account for a highly significant percentage of the particles emitted in many towns and cities. This review is therefore focused on the health effects of diesel exhaust, and especially the particular matter components. Acute effects of diesel exhaust exposure include irritation of the nose and eyes, lung function changes, respiratory changes, headache, fatigue and nausea. Chronic exposures are associated with cough, sputum production and lung function decrements. In addition to symptoms, exposure studies in healthy humans have documented a number of profound inflammatory changes in the airways, notably, before changes in pulmonary function can be detected. It is likely that such effects may be even more detrimental in asthmatics and other subjects with compromised pulmonary function. There are also observations supporting the hypothesis that diesel exhaust is one important factor contributing to the allergy pandemic. For example, in many experimental systems, diesel exhaust particles can be shown to act as adjuvants to allergen and hence increase the sensitization response. Much of the research on adverse effects of diesel exhaust, both in vivo and in vitro, has however been conducted in animals. Questions remain concerning the relevance of exposure levels and whether findings in such models can be extrapolated into humans. It is therefore imperative to further assess acute and chronic effects of diesel exhaust in mechanistic studies with careful consideration of exposure levels. Whenever possible and ethically justified, studies should be carried out in humans.. air pollution| allergy incidence| animal studies| asthma exacerbation| diesel| human exposure|particulate air-pollution| bronchial epithelial-cells| systemic ige production| heart-rate-variability| lung-tissue responses| short-term exposure| in-vitro| cytokine production| allergen challenge| particle retention.	APR-2001	air pollution| allergy incidence| animal studies| asthma exacerbation| diesel| human exposure|particulate air-pollution| bronchial epithelial-cells| systemic ige production| heart-rate-variability| lung-tissue responses| short-term exposure| in-vitro| cytokine production| allergen challenge| particle retention	Sydbom, A; Blomberg, A; Parnia, S; Stenfors, N; Sandstrom, T; Dahlen, SE	Health effects of diesel exhaust emissions		EUROPEAN RESPIRATORY JOURNAL	air pollution; allergy incidence; animal studies; asthma exacerbation; diesel; human exposure	PARTICULATE AIR-POLLUTION; BRONCHIAL EPITHELIAL-CELLS; SYSTEMIC IGE PRODUCTION; HEART-RATE-VARIABILITY; LUNG-TISSUE RESPONSES; SHORT-TERM EXPOSURE; IN-VITRO; CYTOKINE PRODUCTION; ALLERGEN CHALLENGE; PARTICLE RETENTION	Epidemiological studies have demonstrated an association between different levels of air pollution and various health outcomes including mortality, exacerbation of asthma, chronic bronchitis, respiratory tract infections, ischaemic heart disease and stroke. Of the motor vehicle generated air pollutants, diesel exhaust particles account for a highly significant percentage of the particles emitted in many towns and cities. This review is therefore focused on the health effects of diesel exhaust, and especially the particular matter components. Acute effects of diesel exhaust exposure include irritation of the nose and eyes, lung function changes, respiratory changes, headache, fatigue and nausea. Chronic exposures are associated with cough, sputum production and lung function decrements. In addition to symptoms, exposure studies in healthy humans have documented a number of profound inflammatory changes in the airways, notably, before changes in pulmonary function can be detected. It is likely that such effects may be even more detrimental in asthmatics and other subjects with compromised pulmonary function. There are also observations supporting the hypothesis that diesel exhaust is one important factor contributing to the allergy pandemic. For example, in many experimental systems, diesel exhaust particles can be shown to act as adjuvants to allergen and hence increase the sensitization response. Much of the research on adverse effects of diesel exhaust, both in vivo and in vitro, has however been conducted in animals. Questions remain concerning the relevance of exposure levels and whether findings in such models can be extrapolated into humans. It is therefore imperative to further assess acute and chronic effects of diesel exhaust in mechanistic studies with careful consideration of exposure levels. Whenever possible and ethically justified, studies should be carried out in humans.	110	254	2001	14	10.1183/09031936.01.17407330	Respiratory System
Office spirometry for lung health assessment in adults - A consensus statement from the National Lung Health Education Program. COPD is easily detected in its preclinical phase using spirometry, and successful smoking cessation (a cost-effective intervention) prevents further disease progression, This consensus statement recommends the widespread use of office spirometry by primary-care providers for patients greater than or equal to 45 years old who smoke cigarettes. Discussion of the spirometry results with current smokers should be accompanied by strong advice to quit smoking and referral to local smoking cessation resources. Spirometry also is recommended for patients with respiratory symptoms such as chronic cough, episodic wheezing, and exertional dyspnea in order to detect airways obstruction due to asthma or COPD, Although diagnostic-quality spirometry may be used to detect COPD, we recommend the development, validation, and implementation of a new type of spirometry-office spirometry-for this purpose in the primary-care setting, In order to encourage the widespread use of office spirometers, their specifications differ somewhat from those for diagnostic spirometers, allowing lower instrument cost, smaller size, less effort to perform the test, improved ease of calibration checks, and an improved quality-assurance program.. copd| risk assessment| smoking| spirometry|obstructive pulmonary-disease| smoking cessation interventions| air-flow limitation| forced expiratory volume| controlled trial| respiratory symptoms| randomized trial| reference values| general-practice| nicotine patch.	APR-2000	copd| risk assessment| smoking| spirometry|obstructive pulmonary-disease| smoking cessation interventions| air-flow limitation| forced expiratory volume| controlled trial| respiratory symptoms| randomized trial| reference values| general-practice| nicotine patch	Ferguson, GT; Enright, PL; Buist, AS; Higgins, MW	Office spirometry for lung health assessment in adults - A consensus statement from the National Lung Health Education Program		CHEST	COPD; risk assessment; smoking; spirometry	OBSTRUCTIVE PULMONARY-DISEASE; SMOKING CESSATION INTERVENTIONS; AIR-FLOW LIMITATION; FORCED EXPIRATORY VOLUME; CONTROLLED TRIAL; RESPIRATORY SYMPTOMS; RANDOMIZED TRIAL; REFERENCE VALUES; GENERAL-PRACTICE; NICOTINE PATCH	COPD is easily detected in its preclinical phase using spirometry, and successful smoking cessation (a cost-effective intervention) prevents further disease progression, This consensus statement recommends the widespread use of office spirometry by primary-care providers for patients greater than or equal to 45 years old who smoke cigarettes. Discussion of the spirometry results with current smokers should be accompanied by strong advice to quit smoking and referral to local smoking cessation resources. Spirometry also is recommended for patients with respiratory symptoms such as chronic cough, episodic wheezing, and exertional dyspnea in order to detect airways obstruction due to asthma or COPD, Although diagnostic-quality spirometry may be used to detect COPD, we recommend the development, validation, and implementation of a new type of spirometry-office spirometry-for this purpose in the primary-care setting, In order to encourage the widespread use of office spirometers, their specifications differ somewhat from those for diagnostic spirometers, allowing lower instrument cost, smaller size, less effort to perform the test, improved ease of calibration checks, and an improved quality-assurance program.	118	254	2000	18	10.1378/chest.117.4.1146	General & Internal Medicine; Respiratory System
Is vitamin D deficiency to blame for the asthma epidemic?. In the 1960s, the prevalence of asthma and allergic diseases began to increase worldwide. Currently, the burden of the disease is more than 300 million people affected. We hypothesize that as populations grow more prosperous, more time is spent indoors, and there is less exposure to sunlight, leading to decreased cutaneous vitamin D production. Coupled with inadequate intake from foods and supplements, this then leads to vitamin D deficiency, particularly in pregnant women, resulting in more asthma and allergy in their offspring. Vitamin D has been linked to immune system and lung development in utero, and our epiderniologic studies show that higher vitamin D intake by pregnant mothers reduces asthma risk by as much as 40% in children 3 to 5 years old. Vitamin D deficiency has been associated with obesity, African American race (particularly in urban, inner-city settings), and recent immigrants to westernized countries, thus reflecting the epiderniologic patterns observed in the asthma epidemic. Providing adequate vitamin D supplementation in pregnancy may lead to significant decreases in asthma incidence in young children.. asthma| allergy| vitamin d| prevention|regulatory t-cells| nutrition examination survey| 3rd national-health| d-receptor gene| 1-alpha,25-dihydroxyvitamin d-3| 1,25-dihydroxyvitamin d-3| hygiene hypothesis| hypovitaminosis-d| ige production| ii cells.	NOV-2007	asthma| allergy| vitamin d| prevention|regulatory t-cells| nutrition examination survey| 3rd national-health| d-receptor gene| 1-alpha,25-dihydroxyvitamin d-3| 1,25-dihydroxyvitamin d-3| hygiene hypothesis| hypovitaminosis-d| ige production| ii cells	Litonjua, AA; Weiss, ST	Is vitamin D deficiency to blame for the asthma epidemic?		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; allergy; vitamin D; prevention	REGULATORY T-CELLS; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; D-RECEPTOR GENE; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; 1,25-DIHYDROXYVITAMIN D-3; HYGIENE HYPOTHESIS; HYPOVITAMINOSIS-D; IGE PRODUCTION; II CELLS	In the 1960s, the prevalence of asthma and allergic diseases began to increase worldwide. Currently, the burden of the disease is more than 300 million people affected. We hypothesize that as populations grow more prosperous, more time is spent indoors, and there is less exposure to sunlight, leading to decreased cutaneous vitamin D production. Coupled with inadequate intake from foods and supplements, this then leads to vitamin D deficiency, particularly in pregnant women, resulting in more asthma and allergy in their offspring. Vitamin D has been linked to immune system and lung development in utero, and our epiderniologic studies show that higher vitamin D intake by pregnant mothers reduces asthma risk by as much as 40% in children 3 to 5 years old. Vitamin D deficiency has been associated with obesity, African American race (particularly in urban, inner-city settings), and recent immigrants to westernized countries, thus reflecting the epiderniologic patterns observed in the asthma epidemic. Providing adequate vitamin D supplementation in pregnancy may lead to significant decreases in asthma incidence in young children.	75	253	2007	5	10.1016/j.jaci.2007.08.028	Allergy; Immunology
Air pollution and development of asthma, allergy and infections in a birth cohort. Few studies have addressed associations between traffic-related air pollution and respiratory disease in young children. The present authors assessed the development of asthmatic/allergic symptoms and respiratory infections during the first 4 yrs of life in a birth cohort study (n=similar to 4,000). Outdoor concentrations of traffic-related air pollutants (nitrogen dioxide PM2.5, particles with a 50% cut-off aerodynamic diameter of 2.5 mu m and soot) were assigned to birthplace home addresses with a land-use regression model. They were linked by logistic regression to questionnaire data on doctor-diagnosed asthma, bronchitis, influenza and eczema and to self-reported wheeze, dry night-time cough, ear/nose/throat infections and skin rash. Total and specific immunoglobulin (Ig)E to common allergens were measured in a subgroup (n=713). Adjusted odds ratios (95% confidence intervals) per interquartile pollution range were elevated for wheeze (1.2 (1.0-1.4) for soot), doctor-diagnosed asthma (1.3 (1.0-1.7)), ear/nose/throat infections (1.2 (1.0-1.3)) and flu/serious colds (1.2 (1.0-1.4)). No consistent associations were observed for other end-points. Positive associations between air pollution and specific sensitisation to common food allergens (1.6 (1.2-2.2) for soot), but not total IgE, were found in the subgroup with IgE measurements. Traffic-related pollution was associated with respiratory infections and some measures of asthma and allergy during the first 4 yrs of life.. air pollution| allergy| asthma| respiratory infections| vehicle emissions|chronic respiratory symptoms| 3 european areas| total serum ige| childhood asthma| nitrogen-dioxide| preschool-children| school-children| exposure| health| atopy.	MAY-2007	air pollution| allergy| asthma| respiratory infections| vehicle emissions|chronic respiratory symptoms| 3 european areas| total serum ige| childhood asthma| nitrogen-dioxide| preschool-children| school-children| exposure| health| atopy	Brauer, M; Hoek, G; Smit, HA; de Jongste, JC; Gerritsen, J; Postma, DS; Kerkhof, M; Brunekreef, B	Air pollution and development of asthma, allergy and infections in a birth cohort		EUROPEAN RESPIRATORY JOURNAL	air pollution; allergy; asthma; respiratory infections; vehicle emissions	CHRONIC RESPIRATORY SYMPTOMS; 3 EUROPEAN AREAS; TOTAL SERUM IGE; CHILDHOOD ASTHMA; NITROGEN-DIOXIDE; PRESCHOOL-CHILDREN; SCHOOL-CHILDREN; EXPOSURE; HEALTH; ATOPY	Few studies have addressed associations between traffic-related air pollution and respiratory disease in young children. The present authors assessed the development of asthmatic/allergic symptoms and respiratory infections during the first 4 yrs of life in a birth cohort study (n=similar to 4,000). Outdoor concentrations of traffic-related air pollutants (nitrogen dioxide PM2.5, particles with a 50% cut-off aerodynamic diameter of 2.5 mu m and soot) were assigned to birthplace home addresses with a land-use regression model. They were linked by logistic regression to questionnaire data on doctor-diagnosed asthma, bronchitis, influenza and eczema and to self-reported wheeze, dry night-time cough, ear/nose/throat infections and skin rash. Total and specific immunoglobulin (Ig)E to common allergens were measured in a subgroup (n=713). Adjusted odds ratios (95% confidence intervals) per interquartile pollution range were elevated for wheeze (1.2 (1.0-1.4) for soot), doctor-diagnosed asthma (1.3 (1.0-1.7)), ear/nose/throat infections (1.2 (1.0-1.3)) and flu/serious colds (1.2 (1.0-1.4)). No consistent associations were observed for other end-points. Positive associations between air pollution and specific sensitisation to common food allergens (1.6 (1.2-2.2) for soot), but not total IgE, were found in the subgroup with IgE measurements. Traffic-related pollution was associated with respiratory infections and some measures of asthma and allergy during the first 4 yrs of life.	42	253	2007	10	10.1183/09031936.00083406	Respiratory System
Molecular mechanisms in allergy and clinical immunology. Specific allergen injection immunotherapy is highly effective in IgE-mediated diseases, such as allergic rhinitis and venom anaphylaxis. Immunotherapy inhibits both early and late responses to allergen exposure. Immunotherapy is accompanied by increases in allergen-specific IgG, particularly the IgG4 isotype, which blocks not only IgE-dependent histamine release from basophils but also IgE-mediated antigen presentation to T cells. Immunotherapy acts on T cells to modify peripheral and mucosal T(H)2 responses to allergen in favor of T(H)1 responses. Recent studies have identified increased IL-10 production in peripheral blood and mucosal surfaces after immunotherapy. IL-10 has numerous potential antiallergic properties, including suppression of mast cell, eosinophil, and T-cell responses, as well as acting on B cells to favor heavy chain class switching to IgG4. These IL-10-producing cells might be so-called regulatory T cells and appear to be identified by the CD4(+)CD25(+) phenotype. Studies in mice suggest that dendritic cells play a vital role in induction of regulatory T cells. Novel approaches to immunotherapy currently being explored include the use of adjuvants, such as monophosphoryl lipid A or nucleotide immunostimulatory sequences derived from bacteria that potentiate T(H)1 responses. Alternative strategies include the use of allergen-derived peptides; or modified recombinant allergen vaccines that act on T cells while minimizing the IgE-dependent mast cell activation that is dependent on the native allergen conformation.. immunotherapy| allergy| ige| il-10| regulatory t cells|grass-pollen immunotherapy| regulatory t-cells| messenger-rna expression| bee venom immunotherapy| antigen-presenting cell| monophosphoryl-lipid-a| human dendritic cells| igg antibodies| hay-fever| in-vitro.	JUN-2004	immunotherapy| allergy| ige| il-10| regulatory t cells|grass-pollen immunotherapy| regulatory t-cells| messenger-rna expression| bee venom immunotherapy| antigen-presenting cell| monophosphoryl-lipid-a| human dendritic cells| igg antibodies| hay-fever| in-vitro	Till, SJ; Francis, JN; Nouri-Aria, K; Durham, SR	Molecular mechanisms in allergy and clinical immunology		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	immunotherapy; allergy; IgE; IL-10; regulatory T cells	GRASS-POLLEN IMMUNOTHERAPY; REGULATORY T-CELLS; MESSENGER-RNA EXPRESSION; BEE VENOM IMMUNOTHERAPY; ANTIGEN-PRESENTING CELL; MONOPHOSPHORYL-LIPID-A; HUMAN DENDRITIC CELLS; IGG ANTIBODIES; HAY-FEVER; IN-VITRO	Specific allergen injection immunotherapy is highly effective in IgE-mediated diseases, such as allergic rhinitis and venom anaphylaxis. Immunotherapy inhibits both early and late responses to allergen exposure. Immunotherapy is accompanied by increases in allergen-specific IgG, particularly the IgG4 isotype, which blocks not only IgE-dependent histamine release from basophils but also IgE-mediated antigen presentation to T cells. Immunotherapy acts on T cells to modify peripheral and mucosal T(H)2 responses to allergen in favor of T(H)1 responses. Recent studies have identified increased IL-10 production in peripheral blood and mucosal surfaces after immunotherapy. IL-10 has numerous potential antiallergic properties, including suppression of mast cell, eosinophil, and T-cell responses, as well as acting on B cells to favor heavy chain class switching to IgG4. These IL-10-producing cells might be so-called regulatory T cells and appear to be identified by the CD4(+)CD25(+) phenotype. Studies in mice suggest that dendritic cells play a vital role in induction of regulatory T cells. Novel approaches to immunotherapy currently being explored include the use of adjuvants, such as monophosphoryl lipid A or nucleotide immunostimulatory sequences derived from bacteria that potentiate T(H)1 responses. Alternative strategies include the use of allergen-derived peptides; or modified recombinant allergen vaccines that act on T cells while minimizing the IgE-dependent mast cell activation that is dependent on the native allergen conformation.	82	253	2004	10	10.1016/j.jaci.2004.03.024	Allergy; Immunology
House dust endotoxin and wheeze in the first year of life. We examined endotoxin exposure and wheezing episodes during the first year of life in a birth cohort of 499 infants with one or both parents having a history of asthma or allergy. We measured endotoxin in settled dust from the baby's bed, bedroom floor, family room, and kitchen floor within the first 3 mo after birth. The primary outcomes were any wheeze (versus no wheeze), and repeated wheeze (versus one or no report of wheeze). We found a significant univariate association of elevated endotoxin (greater than or equal to 100 EU/mg) in family room dust with increased risk of any wheeze (Relative Risk = 1.29, 95% CI = 1.03-1.62). The association was not confounded by cockroach allergen, lower respiratory illness (croup, bronchitis, bronchiolitis, and pneumonia), smoking during pregnancy, tower birth weight, maternal asthma, presence of dog, and race/ethnicity in a multivariate model; the multivariate relative risk (RR = 1.33) was marginally significant (95% CI: 1.00-1.76, p < 0.05). In a multivariate model, controlling for the above covariates, elevated endotoxin in family room dust was significantly associated with increased risk (RR = 1.56, 95% CI = 1.03-2.38) of repeated wheeze. These results suggest that home endotoxin exposure may independently increase risk of any wheeze and repeated wheeze during the first year of life for children with a familial predisposition to asthma or allergy.. lung-function| lipopolysaccharide lps| respiratory illness| limulus assay| grain dust| asthma| exposure| inhalation| interleukin-1| sensitization.	FEB-2001	lung-function| lipopolysaccharide lps| respiratory illness| limulus assay| grain dust| asthma| exposure| inhalation| interleukin-1| sensitization	Park, JH; Gold, DR; Spiegelman, DL; Burge, HA; Milton, DK	House dust endotoxin and wheeze in the first year of life		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		LUNG-FUNCTION; LIPOPOLYSACCHARIDE LPS; RESPIRATORY ILLNESS; LIMULUS ASSAY; GRAIN DUST; ASTHMA; EXPOSURE; INHALATION; INTERLEUKIN-1; SENSITIZATION	We examined endotoxin exposure and wheezing episodes during the first year of life in a birth cohort of 499 infants with one or both parents having a history of asthma or allergy. We measured endotoxin in settled dust from the baby's bed, bedroom floor, family room, and kitchen floor within the first 3 mo after birth. The primary outcomes were any wheeze (versus no wheeze), and repeated wheeze (versus one or no report of wheeze). We found a significant univariate association of elevated endotoxin (greater than or equal to 100 EU/mg) in family room dust with increased risk of any wheeze (Relative Risk = 1.29, 95% CI = 1.03-1.62). The association was not confounded by cockroach allergen, lower respiratory illness (croup, bronchitis, bronchiolitis, and pneumonia), smoking during pregnancy, tower birth weight, maternal asthma, presence of dog, and race/ethnicity in a multivariate model; the multivariate relative risk (RR = 1.33) was marginally significant (95% CI: 1.00-1.76, p < 0.05). In a multivariate model, controlling for the above covariates, elevated endotoxin in family room dust was significantly associated with increased risk (RR = 1.56, 95% CI = 1.03-2.38) of repeated wheeze. These results suggest that home endotoxin exposure may independently increase risk of any wheeze and repeated wheeze during the first year of life for children with a familial predisposition to asthma or allergy.	35	253	2001	7		General & Internal Medicine; Respiratory System
Relation of body mass index to asthma and atopy in children: the National Health and Nutrition Examination Study III. Background-An increase in the prevalence of obesity and asthma over recent decades has been reported in affluent societies. Both overweight and obesity have been shown to be inversely related to having been breastfed, which is also a potential protective factor against childhood atopic diseases. The aim of this analysis was to explore the relation of body mass index (BMI) to asthma and atopy in a large representative sample of the United States population. Methods-Children aged 4-17 years were included in the NHANES III survey. Prevalences of atopic diseases and potential confounding factors such as exposure to environmental tobacco smoke, birth weight, breast feeding, and household size were assessed using structured interviews with parents. Height and weight were measured, and BMI was calculated as kg/m(2) and transformed into Z scores. Children underwent skin prick tests for atopy to a battery of food and inhalant allergens. Results-The prevalence of asthma (8.7% v 9.3% v 10.3% v 14.9%, p=0.0001) and atopy (48.6% v 50.5% v 53.0% v 53.2%, p=0.05) rose significantly with increasing quartiles of BMI. After adjustment for confounders, a significant positive association between BMI and asthma remained (adjusted OR 1.77, 95% confidence interval 1.44 to 2.19 between the highest and lowest quartiles of BMI), whereas no independent relation between BMI and atopy was evident. No effect modification by sex or ethnic group was seen. Conclusions-The effects of increased BMI on asthma may be mediated by mechanical properties of the respiratory system associated with obesity or by upregulation of inflammatory mechanisms rather than by allergic eosinophilic inflammation of the airway epithelium.. body mass index| obesity| atopy| asthma|overweight| obesity| weight| association| childhood| prevalence| adults| age| old.	NOV-2001	body mass index| obesity| atopy| asthma|overweight| obesity| weight| association| childhood| prevalence| adults| age| old	von Mutius, E; Schwartz, J; Neas, LM; Dockery, D; Weiss, ST	Relation of body mass index to asthma and atopy in children: the National Health and Nutrition Examination Study III		THORAX	body mass index; obesity; atopy; asthma	OVERWEIGHT; OBESITY; WEIGHT; ASSOCIATION; CHILDHOOD; PREVALENCE; ADULTS; AGE; OLD	Background-An increase in the prevalence of obesity and asthma over recent decades has been reported in affluent societies. Both overweight and obesity have been shown to be inversely related to having been breastfed, which is also a potential protective factor against childhood atopic diseases. The aim of this analysis was to explore the relation of body mass index (BMI) to asthma and atopy in a large representative sample of the United States population. Methods-Children aged 4-17 years were included in the NHANES III survey. Prevalences of atopic diseases and potential confounding factors such as exposure to environmental tobacco smoke, birth weight, breast feeding, and household size were assessed using structured interviews with parents. Height and weight were measured, and BMI was calculated as kg/m(2) and transformed into Z scores. Children underwent skin prick tests for atopy to a battery of food and inhalant allergens. Results-The prevalence of asthma (8.7% v 9.3% v 10.3% v 14.9%, p=0.0001) and atopy (48.6% v 50.5% v 53.0% v 53.2%, p=0.05) rose significantly with increasing quartiles of BMI. After adjustment for confounders, a significant positive association between BMI and asthma remained (adjusted OR 1.77, 95% confidence interval 1.44 to 2.19 between the highest and lowest quartiles of BMI), whereas no independent relation between BMI and atopy was evident. No effect modification by sex or ethnic group was seen. Conclusions-The effects of increased BMI on asthma may be mediated by mechanical properties of the respiratory system associated with obesity or by upregulation of inflammatory mechanisms rather than by allergic eosinophilic inflammation of the airway epithelium.	22	252	2001	4	10.1136/thorax.56.11.835	Respiratory System
The effect of common polymorphisms of the beta(2)-adrenergic receptor on agonist-mediated vascular desensitization. Background: With continuous exposure to beta (2)-adrenergic agonists, vascular tissue becomes desensitized to agonist-mediated vasodilatation. We studied the effects of two common polymorphisms of the beta (2)-adrenergic receptor, one at codon 16 and one at codon 27, on agonist-mediated vasodilatation and desensitization in the vascular bed. Methods: We studied 26 healthy subjects who were selected to represent three genotypes: 7 were homozygous for the alleles encoding Arg16 and GIn27, 8 were homozygous for the alleles encoding Gly16 and Gln27, and 11 were homozygous for the alleles encoding Gly16 and Glu27. Vascular responses were assessed by measuring changes in the diameter of a dorsal hand vein. A dose-response curve of the effect of the beta (2)-adrenergic-receptor agonist isoproterenol was constructed (dose range, 4 to 480 ng per minute). Desensitization was then induced by a 2-hour continuous infusion of isoproterenol, and venodilatation was measured 30, 60, 90, and 120 minutes after the start of the infusion. Results: Subjects who were homozygous for Arg16 had almost complete desensitization; venodilatation in response to isoproterenol in this group decreased from a mean (+/-SE) of 44+/-11 percent to 8+/-4 percent (P=0.006). In contrast, subjects who were homozygous for Gly16 did not have significant desensitization, irrespective of the amino acid encoded by codon 27. Subjects who were homozygous for Glu27 had higher maximal venodilatation in response to isoproterenol than those who were homozygous for Gln27 (86+/-13 percent vs. 54+/-8 percent, P=0.03). Conclusions: The Arg16 polymorphism of the beta (2)-adrenergic receptor is associated with enhanced agonist-mediated desensitization in the vasculature, and the Glu27 polymorphism is associated with increased agonist-mediated responsiveness. Therefore, polymorphisms of the beta (2)-adrenergic receptor are potentially important determinants of the vascular response to stress. (N Engl J Med 2001;345:1030-5.) Copyright (C) 2001 Massachusetts Medical Society.. beta-2-adrenergic receptor| adult-population| blood-pressure| hypertension| vasodilation| asthma| individuals| cells.	OCT 4-2001	beta-2-adrenergic receptor| adult-population| blood-pressure| hypertension| vasodilation| asthma| individuals| cells	Dishy, V; Sofowora, GG; Xie, HG; Kim, RB; Byrne, DW; Stein, CM; Wood, AJJ	The effect of common polymorphisms of the beta(2)-adrenergic receptor on agonist-mediated vascular desensitization		NEW ENGLAND JOURNAL OF MEDICINE		BETA-2-ADRENERGIC RECEPTOR; ADULT-POPULATION; BLOOD-PRESSURE; HYPERTENSION; VASODILATION; ASTHMA; INDIVIDUALS; CELLS	Background: With continuous exposure to beta (2)-adrenergic agonists, vascular tissue becomes desensitized to agonist-mediated vasodilatation. We studied the effects of two common polymorphisms of the beta (2)-adrenergic receptor, one at codon 16 and one at codon 27, on agonist-mediated vasodilatation and desensitization in the vascular bed. Methods: We studied 26 healthy subjects who were selected to represent three genotypes: 7 were homozygous for the alleles encoding Arg16 and GIn27, 8 were homozygous for the alleles encoding Gly16 and Gln27, and 11 were homozygous for the alleles encoding Gly16 and Glu27. Vascular responses were assessed by measuring changes in the diameter of a dorsal hand vein. A dose-response curve of the effect of the beta (2)-adrenergic-receptor agonist isoproterenol was constructed (dose range, 4 to 480 ng per minute). Desensitization was then induced by a 2-hour continuous infusion of isoproterenol, and venodilatation was measured 30, 60, 90, and 120 minutes after the start of the infusion. Results: Subjects who were homozygous for Arg16 had almost complete desensitization; venodilatation in response to isoproterenol in this group decreased from a mean (+/-SE) of 44+/-11 percent to 8+/-4 percent (P=0.006). In contrast, subjects who were homozygous for Gly16 did not have significant desensitization, irrespective of the amino acid encoded by codon 27. Subjects who were homozygous for Glu27 had higher maximal venodilatation in response to isoproterenol than those who were homozygous for Gln27 (86+/-13 percent vs. 54+/-8 percent, P=0.03). Conclusions: The Arg16 polymorphism of the beta (2)-adrenergic receptor is associated with enhanced agonist-mediated desensitization in the vasculature, and the Glu27 polymorphism is associated with increased agonist-mediated responsiveness. Therefore, polymorphisms of the beta (2)-adrenergic receptor are potentially important determinants of the vascular response to stress. (N Engl J Med 2001;345:1030-5.) Copyright (C) 2001 Massachusetts Medical Society.	28	252	2001	6	10.1056/NEJMoa010819	General & Internal Medicine
Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children. Background: There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role. Objective: We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring. Methods: In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toil-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information. Results: Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% Cl, 1.04-1.2), and 1.10 (95% Cl, 1.03-1.23), respectively. Conclusion: Maternal exposure to an environment rich in microbial compounds might protect against the development of atopic sensitization and lead to upregulation of receptors of the innate immune system. The underlying mechanisms potentially operating through the intrauterine milieu or epigenetic inheritance await further elucidation. Clinical implications: When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.. asthma| allergy| atopic sensitization| gene expression| toll-like receptors| cd14| farming| maternal exposure| microbial exposure|toll-like receptors| day-care attendance| house-dust| early-life| maternal history| childhood asthma| risk| pregnancy| smoking| schoolchildren.	APR-2006	asthma| allergy| atopic sensitization| gene expression| toll-like receptors| cd14| farming| maternal exposure| microbial exposure|toll-like receptors| day-care attendance| house-dust| early-life| maternal history| childhood asthma| risk| pregnancy| smoking| schoolchildren	Ege, MJ; Bieli, C; Frei, R; van Strien, RT; Riedler, J; Ublagger, E; Schram-Bijkerk, D; Brunekreef, B; van Hage, M; Scheynius, A; Pershagen, G; Benz, MR; Lauener, R; von Mutius, E; Braun-Fahrlander, C	Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; allergy; atopic sensitization; gene expression; Toll-like receptors; CD14; farming; maternal exposure; microbial exposure	TOLL-LIKE RECEPTORS; DAY-CARE ATTENDANCE; HOUSE-DUST; EARLY-LIFE; MATERNAL HISTORY; CHILDHOOD ASTHMA; RISK; PREGNANCY; SMOKING; SCHOOLCHILDREN	Background: There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role. Objective: We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring. Methods: In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toil-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information. Results: Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% Cl, 1.04-1.2), and 1.10 (95% Cl, 1.03-1.23), respectively. Conclusion: Maternal exposure to an environment rich in microbial compounds might protect against the development of atopic sensitization and lead to upregulation of receptors of the innate immune system. The underlying mechanisms potentially operating through the intrauterine milieu or epigenetic inheritance await further elucidation. Clinical implications: When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.	36	251	2006	7	10.1016/j.jaci.2005.12.1307	Allergy; Immunology
Sublingual immunotherapy: A comprehensive review. Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is viewed with increasing interest by allergists in the United States. To address this interest, a Joint Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's Immunotherapy and Allergy Diagnostic Committees reviewed the available literature on SLIT and prepared this report. The task force concluded that despite clear evidence that SLIT is an effective treatment, many questions remained unanswered, including effective dose, treatment schedules, and overall duration of treatment. Until these have been determined, an assessment of the cost/benefit ratio of the treatment cannot be made. SLIT does appear to be associated with few serious side effects, but it has not been administered in high-risk asthmatic patients, nor in the studies reviewed has it been administered as a mixture of non-cross-reacting allergens. Furthermore, there is currently no allergy extract approved for this use in the United States, nor is there a Current Procedural Terminology code for billing purposes. All of these factors should be given careful consideration by anyone contemplating initiating SLIT treatment for their allergic patients.. sublingual-swallow immunotherapy| sublingual-spit immunotherapy| allergen immunotherapy| allergic asthma| allergic rhinitis|randomized controlled-trial| double-blind placebo| house-dust mites| seasonal allergic rhinoconjunctivitis| standardized 5-grass-pollen extract| grass-pollen extract| swallow immunotherapy| systemic reactions| respiratory allergy| rush immunotherapy.	MAY-2006	sublingual-swallow immunotherapy| sublingual-spit immunotherapy| allergen immunotherapy| allergic asthma| allergic rhinitis|randomized controlled-trial| double-blind placebo| house-dust mites| seasonal allergic rhinoconjunctivitis| standardized 5-grass-pollen extract| grass-pollen extract| swallow immunotherapy| systemic reactions| respiratory allergy| rush immunotherapy	Cox, LS; Linnemann, DL; Nolte, H; Weldon, D; Finegold, I; Nelson, HS	Sublingual immunotherapy: A comprehensive review		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	sublingual-swallow immunotherapy; sublingual-spit immunotherapy; allergen immunotherapy; allergic asthma; allergic rhinitis	RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND PLACEBO; HOUSE-DUST MITES; SEASONAL ALLERGIC RHINOCONJUNCTIVITIS; STANDARDIZED 5-GRASS-POLLEN EXTRACT; GRASS-POLLEN EXTRACT; SWALLOW IMMUNOTHERAPY; SYSTEMIC REACTIONS; RESPIRATORY ALLERGY; RUSH IMMUNOTHERAPY	Sublingual immunotherapy (SLIT) has been used with increasing frequency in Europe and is viewed with increasing interest by allergists in the United States. To address this interest, a Joint Task Force of the American College of Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and Immunology's Immunotherapy and Allergy Diagnostic Committees reviewed the available literature on SLIT and prepared this report. The task force concluded that despite clear evidence that SLIT is an effective treatment, many questions remained unanswered, including effective dose, treatment schedules, and overall duration of treatment. Until these have been determined, an assessment of the cost/benefit ratio of the treatment cannot be made. SLIT does appear to be associated with few serious side effects, but it has not been administered in high-risk asthmatic patients, nor in the studies reviewed has it been administered as a mixture of non-cross-reacting allergens. Furthermore, there is currently no allergy extract approved for this use in the United States, nor is there a Current Procedural Terminology code for billing purposes. All of these factors should be given careful consideration by anyone contemplating initiating SLIT treatment for their allergic patients.	121	250	2006	15	10.1016/j.jaci.2006.02.040	Allergy; Immunology
The European Community Respiratory Health Survey: what are the main results so far?. The European Community Respiratory Heath Survey (ECRHS) was the first study to assess the geographical variation in asthma and allergy in adults using the same instruments and definitions. The database of the ECRHS includes information from similar to 140,000 individuals from 22 countries. The aim of this review is to summarize the results of the ECRHS to date. The ECRHS has shown that there are large geographical differences in the prevalence of asthma, atopy and bronchial responsiveness, with high prevalence rates in English speaking countries and low prevalence rates in the Mediterranean region and Eastern Europe. Analyses of risk factors have highlighted the importance of occupational exposure for asthma in adulthood. The association between sensitization to individual allergens and bronchial responsiveness was strongest for indoor allergens (mite and cat). Analysis of treatment practices has confirmed that the treatment of asthma varies widely between countries and that asthma is often undertreated. In conclusion, the European Community Respiratory Health Survey has shown that the prevalence of asthma varies widely. The fact that the geographical pattern is consistent with the distribution of atopy and bronchial responsiveness supports the conclusion that the geographical variations in the prevalence of asthma are true and most likely due to environmental factors.. asthma| atopy| epidemiology| incidence| prevalence| risk factors|asthma-like symptoms| volatile organic-compounds| total serum ige| young-adults| bronchial hyperresponsiveness| atopic sensitization| lung-function| individual allergens| occupational asthma| reported asthma.	SEP-2001	asthma| atopy| epidemiology| incidence| prevalence| risk factors|asthma-like symptoms| volatile organic-compounds| total serum ige| young-adults| bronchial hyperresponsiveness| atopic sensitization| lung-function| individual allergens| occupational asthma| reported asthma	Janson, C; Anto, J; Burney, P; Chinn, S; de Marco, R; Heinrich, J; Jarvis, D; Kuenzli, N; Leynaert, B; Luczynska, C; Neukirch, F; Svanes, C; Sunyer, J; Wjst, M	The European Community Respiratory Health Survey: what are the main results so far?		EUROPEAN RESPIRATORY JOURNAL	asthma; atopy; epidemiology; incidence; prevalence; risk factors	ASTHMA-LIKE SYMPTOMS; VOLATILE ORGANIC-COMPOUNDS; TOTAL SERUM IGE; YOUNG-ADULTS; BRONCHIAL HYPERRESPONSIVENESS; ATOPIC SENSITIZATION; LUNG-FUNCTION; INDIVIDUAL ALLERGENS; OCCUPATIONAL ASTHMA; REPORTED ASTHMA	The European Community Respiratory Heath Survey (ECRHS) was the first study to assess the geographical variation in asthma and allergy in adults using the same instruments and definitions. The database of the ECRHS includes information from similar to 140,000 individuals from 22 countries. The aim of this review is to summarize the results of the ECRHS to date. The ECRHS has shown that there are large geographical differences in the prevalence of asthma, atopy and bronchial responsiveness, with high prevalence rates in English speaking countries and low prevalence rates in the Mediterranean region and Eastern Europe. Analyses of risk factors have highlighted the importance of occupational exposure for asthma in adulthood. The association between sensitization to individual allergens and bronchial responsiveness was strongest for indoor allergens (mite and cat). Analysis of treatment practices has confirmed that the treatment of asthma varies widely between countries and that asthma is often undertreated. In conclusion, the European Community Respiratory Health Survey has shown that the prevalence of asthma varies widely. The fact that the geographical pattern is consistent with the distribution of atopy and bronchial responsiveness supports the conclusion that the geographical variations in the prevalence of asthma are true and most likely due to environmental factors.	104	249	2001	14	10.1183/09031936.01.00205801	Respiratory System
Childhood asthma and exposure to traffic and nitrogen dioxide. Background: Evidence for a causal relationship between traffic-related air pollution and asthma has not been consistent across studies, and comparisons among studies have been difficult because of the use of different indicators of exposure. Methods: We examined the association between traffic-related pollution and childhood asthma in 208 children from 10 southern California communities using multiple indicators of exposure. Study subjects were randomly selected from participants in the Children's Health Study. Outdoor nitrogen dioxide (NO2) was measured in summer and winter outside the home of each child. We also determined residential distance to the nearest freeway, traffic volumes on roadways within 150 meters, and model-based estimates of pollution from nearby roadways. Results: Lifetime history of doctor-diagnosed asthma was associated with outdoor NO2; the odds ratio (OR) was 1.83 (95% confidence interval = 1.04-3.22) per increase of 1 interquartile range (IQR = 5.7 ppb) in exposure. We also observed increased asthma associated with closer residential distance to a freeway (1.89 per IQR; 1.19-3.02) and with model-based estimates of outdoor pollution from a freeway (2.22 per IQR; 1.36-3.63). These 2 indicators of freeway exposure and measured NO2 concentrations were also associated with wheezing and use of asthma medication. Asthma was not associated with traffic volumes on roadways within 150 meters of homes or with model-based estimates of pollution from nonfreeway roads. Conclusions: These results indicate that respiratory health in children is adversely affected by local exposures to outdoor NO2 or other freeway-related pollutants.. southern california children| air-pollution| bronchitic symptoms| preschool-children| respiratory health| school-children| atopy| road| prevalence| particles.	NOV-2005	southern california children| air-pollution| bronchitic symptoms| preschool-children| respiratory health| school-children| atopy| road| prevalence| particles	Gauderman, WJ; Avol, E; Lurmann, F; Kuenzli, N; Gilliland, F; Peters, J; McConnell, R	Childhood asthma and exposure to traffic and nitrogen dioxide		EPIDEMIOLOGY		SOUTHERN CALIFORNIA CHILDREN; AIR-POLLUTION; BRONCHITIC SYMPTOMS; PRESCHOOL-CHILDREN; RESPIRATORY HEALTH; SCHOOL-CHILDREN; ATOPY; ROAD; PREVALENCE; PARTICLES	Background: Evidence for a causal relationship between traffic-related air pollution and asthma has not been consistent across studies, and comparisons among studies have been difficult because of the use of different indicators of exposure. Methods: We examined the association between traffic-related pollution and childhood asthma in 208 children from 10 southern California communities using multiple indicators of exposure. Study subjects were randomly selected from participants in the Children's Health Study. Outdoor nitrogen dioxide (NO2) was measured in summer and winter outside the home of each child. We also determined residential distance to the nearest freeway, traffic volumes on roadways within 150 meters, and model-based estimates of pollution from nearby roadways. Results: Lifetime history of doctor-diagnosed asthma was associated with outdoor NO2; the odds ratio (OR) was 1.83 (95% confidence interval = 1.04-3.22) per increase of 1 interquartile range (IQR = 5.7 ppb) in exposure. We also observed increased asthma associated with closer residential distance to a freeway (1.89 per IQR; 1.19-3.02) and with model-based estimates of outdoor pollution from a freeway (2.22 per IQR; 1.36-3.63). These 2 indicators of freeway exposure and measured NO2 concentrations were also associated with wheezing and use of asthma medication. Asthma was not associated with traffic volumes on roadways within 150 meters of homes or with model-based estimates of pollution from nonfreeway roads. Conclusions: These results indicate that respiratory health in children is adversely affected by local exposures to outdoor NO2 or other freeway-related pollutants.	40	248	2005	7	10.1097/01.ede.00001813087.51440.75	Public, Environmental & Occupational Health
Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. Interleukin (IL)-17 is produced by activated memory CD4(+) cells and induces cytokines and chemokines that stimulate neutrophil generation and recruitment. Here, we investigated the involvement of IL-17 in the bronchial influx of neutrophils in experimental allergic asthma. Inhalation of nebulized ovalbumin (OVA) by sensitized mice with bronchial eosinophilic inflammation resulting from chronic OVA exposure induced early IL-17 mRNA expression in inflamed lung tissue, concomitant with a prominent bronchial neutrophilic influx. Anti-IL-17 monoclonal antibodies (mAb) injected before allergen inhalation strongly reduced bronchial neutrophilic influx, in a manner equally as potent as the anti-inflammatory dexamethasone. Remarkably, anti-IL-17 mAb significantly enhanced IL-5 levels in both BAL fluid and serum, and aggravated allergen-induced bronchial eosinophilia. In another series of experiments, anti-IL-17 mAb were given repeatedly during the inhalatory challenge phase with OVA of sensitized mice. This treatment regimen abated bronchial neutrophilia in parallel with reduction of bone marrow and blood neutrophilia. In addition, anti-IL-17 mAb treatment elevated eosinophil counts in the bone marrow and bronchial IL-5 production, without alteration of allergen-induced bronchial hyperresponsiveness. In summary, our results demonstrate that IL-17 expression in airways is upregulated upon allergen inhalation, and constitutes the link between allergen-induced T cell activation and neutrophilic influx. Because neutrophils may be important in airway remodeling in chronic severe asthma, targeting IL-17 may hold therapeutic potential in human asthma.. tumor-necrosis-factor| neutrophil recruitment| human keratinocytes| epithelial-cells| tnf-alpha| in-vivo| t-cell| chemotactic protein-2| il-17| expression.	JAN-2003	tumor-necrosis-factor| neutrophil recruitment| human keratinocytes| epithelial-cells| tnf-alpha| in-vivo| t-cell| chemotactic protein-2| il-17| expression	Hellings, PW; Kasran, A; Liu, ZJ; Vandekerckhove, P; Wuyts, A; Overbergh, L; Mathieu, C; Ceuppens, JL	Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		TUMOR-NECROSIS-FACTOR; NEUTROPHIL RECRUITMENT; HUMAN KERATINOCYTES; EPITHELIAL-CELLS; TNF-ALPHA; IN-VIVO; T-CELL; CHEMOTACTIC PROTEIN-2; IL-17; EXPRESSION	Interleukin (IL)-17 is produced by activated memory CD4(+) cells and induces cytokines and chemokines that stimulate neutrophil generation and recruitment. Here, we investigated the involvement of IL-17 in the bronchial influx of neutrophils in experimental allergic asthma. Inhalation of nebulized ovalbumin (OVA) by sensitized mice with bronchial eosinophilic inflammation resulting from chronic OVA exposure induced early IL-17 mRNA expression in inflamed lung tissue, concomitant with a prominent bronchial neutrophilic influx. Anti-IL-17 monoclonal antibodies (mAb) injected before allergen inhalation strongly reduced bronchial neutrophilic influx, in a manner equally as potent as the anti-inflammatory dexamethasone. Remarkably, anti-IL-17 mAb significantly enhanced IL-5 levels in both BAL fluid and serum, and aggravated allergen-induced bronchial eosinophilia. In another series of experiments, anti-IL-17 mAb were given repeatedly during the inhalatory challenge phase with OVA of sensitized mice. This treatment regimen abated bronchial neutrophilia in parallel with reduction of bone marrow and blood neutrophilia. In addition, anti-IL-17 mAb treatment elevated eosinophil counts in the bone marrow and bronchial IL-5 production, without alteration of allergen-induced bronchial hyperresponsiveness. In summary, our results demonstrate that IL-17 expression in airways is upregulated upon allergen inhalation, and constitutes the link between allergen-induced T cell activation and neutrophilic influx. Because neutrophils may be important in airway remodeling in chronic severe asthma, targeting IL-17 may hold therapeutic potential in human asthma.	51	248	2003	9	10.1165/rcmb.4832	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Oxidative stress in allergic respiratory diseases. There is ample evidence that allergic disorders, such as asthma, rhinitis, and atopic dermatitis, are mediated by oxidative stress. Excessive exposure to reactive oxygen and nitrogen species is the hallmark of oxidative stress and leads to damage of proteins, lipids, and DNA. Oxidative stress occurs not only as a result of inflammation but also from environmental exposure to air pollution and cigarette smoke. The specific localization of antioxidant enzymes in the lung and the rapid reaction of nitric oxide with reactive oxygen species, such as superoxide, suggest that antioxidant enzymes might also function as cell-signaling agents or regulators of cell signaling. Therapeutic interventions that decrease exposure to environmental reactive oxygen species or augment endogenous antioxidant defenses might be beneficial as adjunctive therapies for allergic respiratory disorders.. antioxidants| asthma| superoxide dismutase| oxidative stress|extracellular-superoxide dismutase| exhaled hydrogen-peroxide| oxygen radical production| nitric-oxide synthase| airway smooth-muscle| asthmatic-patients| atopic-dermatitis| nitrotyrosine formation| antioxidant status| breath condensate.	SEP-2002	antioxidants| asthma| superoxide dismutase| oxidative stress|extracellular-superoxide dismutase| exhaled hydrogen-peroxide| oxygen radical production| nitric-oxide synthase| airway smooth-muscle| asthmatic-patients| atopic-dermatitis| nitrotyrosine formation| antioxidant status| breath condensate	Bowler, RP; Crapo, JD	Oxidative stress in allergic respiratory diseases		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	antioxidants; asthma; superoxide dismutase; oxidative stress	EXTRACELLULAR-SUPEROXIDE DISMUTASE; EXHALED HYDROGEN-PEROXIDE; OXYGEN RADICAL PRODUCTION; NITRIC-OXIDE SYNTHASE; AIRWAY SMOOTH-MUSCLE; ASTHMATIC-PATIENTS; ATOPIC-DERMATITIS; NITROTYROSINE FORMATION; ANTIOXIDANT STATUS; BREATH CONDENSATE	There is ample evidence that allergic disorders, such as asthma, rhinitis, and atopic dermatitis, are mediated by oxidative stress. Excessive exposure to reactive oxygen and nitrogen species is the hallmark of oxidative stress and leads to damage of proteins, lipids, and DNA. Oxidative stress occurs not only as a result of inflammation but also from environmental exposure to air pollution and cigarette smoke. The specific localization of antioxidant enzymes in the lung and the rapid reaction of nitric oxide with reactive oxygen species, such as superoxide, suggest that antioxidant enzymes might also function as cell-signaling agents or regulators of cell signaling. Therapeutic interventions that decrease exposure to environmental reactive oxygen species or augment endogenous antioxidant defenses might be beneficial as adjunctive therapies for allergic respiratory disorders.	85	248	2002	8	10.1067/mai.2002.126780	Allergy; Immunology
Conventional and Monocyte-Derived CD11b(+) Dendritic Cells Initiate and Maintain T Helper 2 Cell-Mediated Immunity to House Dust Mite Allergen. Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b(+) monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b(+) cDCs but not CD103(+) cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l(-/-) mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b(+) cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung.. chemokine receptor ccr2| airway inflammation| th2 responses| inhaled allergens| viral-infection| lymph-nodes| bone-marrow| uric-acid| t-cells| mice.	FEB 21-2013	chemokine receptor ccr2| airway inflammation| th2 responses| inhaled allergens| viral-infection| lymph-nodes| bone-marrow| uric-acid| t-cells| mice	Plantinga, M; Guilliams, M; Vanheerswynghels, M; Deswarte, K; Branco-Madeira, F; Toussaint, W; Vanhoutte, L; Neyt, K; Killeen, N; Malissen, B; Hammad, H; Lambrecht, BN	Conventional and Monocyte-Derived CD11b(+) Dendritic Cells Initiate and Maintain T Helper 2 Cell-Mediated Immunity to House Dust Mite Allergen		IMMUNITY		CHEMOKINE RECEPTOR CCR2; AIRWAY INFLAMMATION; TH2 RESPONSES; INHALED ALLERGENS; VIRAL-INFECTION; LYMPH-NODES; BONE-MARROW; URIC-ACID; T-CELLS; MICE	Dendritic cells (DCs) are crucial for mounting allergic airway inflammation, but it is unclear which subset of DCs performs this task. By using CD64 and MAR-1 staining, we reliably separated CD11b(+) monocyte-derived DCs (moDCs) from conventional DCs (cDCs) and studied antigen uptake, migration, and presentation assays of lung and lymph node (LN) DCs in response to inhaled house dust mite (HDM). Mainly CD11b(+) cDCs but not CD103(+) cDCs induced T helper 2 (Th2) cell immunity in HDM-specific T cells in vitro and asthma in vivo. Studies in Flt3l(-/-) mice, lacking all cDCs, revealed that moDCs were also sufficient to induce Th2 cell-mediated immunity but only when high-dose HDM was given. The main function of moDCs was the production of proinflammatory chemokines and allergen presentation in the lung during challenge. Thus, we have identified migratory CD11b(+) cDCs as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung.	42	246	2013	14	10.1016/j.immuni.2012.10.016	Immunology
The overlap syndrome of asthma and COPD: what are its features and how important is it?. There is a need to re-evaluate the concept of asthma and chronic obstructive pulmonary disease (COPD) as separate conditions, and to consider situations when they may coexist, or when one condition may evolve into the other. Epidemiological studies show that in older people with obstructive airway disease, as many as half or more may have overlapping diagnoses of asthma and COPD (overlap syndrome). These people are typically excluded from current therapy trials, which limit the generalisability of these trials, and this presents a problem for evidence-based guidelines for obstructive airway diseases. Studying overlap syndrome may shed light on the mechanisms of COPD development. Overlap syndrome is recognised by the coexistence of increased variability of airflow in a patient with incompletely reversible airway obstruction. Patients typically have inflammatory features that resemble COPD, with increased airway neutrophilia, as well as features of airway wall remodelling. Overlap syndrome can develop when there is accelerated decline in lung function, or incomplete lung growth, or both. The risk factors for these events are shared, such that increasing age, bronchial hyper-responsiveness, tobacco smoke exposure, asthma and lower respiratory infections/exacerbations are significant risk factors for both incomplete lung growth and accelerated loss of lung function. Studying these events may offer new insights into the mechanisms and treatment of obstructive airway diseases.. air-flow obstruction| pulmonary-function tests| lung-function decline| risk-factors| follow-up| respiratory symptoms| bronchial hyperresponsiveness| computed-tomography| cigarette-smoking| parental smoking.	AUG-2009	air-flow obstruction| pulmonary-function tests| lung-function decline| risk-factors| follow-up| respiratory symptoms| bronchial hyperresponsiveness| computed-tomography| cigarette-smoking| parental smoking	Gibson, PG; Simpson, JL	The overlap syndrome of asthma and COPD: what are its features and how important is it?		THORAX		AIR-FLOW OBSTRUCTION; PULMONARY-FUNCTION TESTS; LUNG-FUNCTION DECLINE; RISK-FACTORS; FOLLOW-UP; RESPIRATORY SYMPTOMS; BRONCHIAL HYPERRESPONSIVENESS; COMPUTED-TOMOGRAPHY; CIGARETTE-SMOKING; PARENTAL SMOKING	There is a need to re-evaluate the concept of asthma and chronic obstructive pulmonary disease (COPD) as separate conditions, and to consider situations when they may coexist, or when one condition may evolve into the other. Epidemiological studies show that in older people with obstructive airway disease, as many as half or more may have overlapping diagnoses of asthma and COPD (overlap syndrome). These people are typically excluded from current therapy trials, which limit the generalisability of these trials, and this presents a problem for evidence-based guidelines for obstructive airway diseases. Studying overlap syndrome may shed light on the mechanisms of COPD development. Overlap syndrome is recognised by the coexistence of increased variability of airflow in a patient with incompletely reversible airway obstruction. Patients typically have inflammatory features that resemble COPD, with increased airway neutrophilia, as well as features of airway wall remodelling. Overlap syndrome can develop when there is accelerated decline in lung function, or incomplete lung growth, or both. The risk factors for these events are shared, such that increasing age, bronchial hyper-responsiveness, tobacco smoke exposure, asthma and lower respiratory infections/exacerbations are significant risk factors for both incomplete lung growth and accelerated loss of lung function. Studying these events may offer new insights into the mechanisms and treatment of obstructive airway diseases.	53	246	2009	8	10.1136/thx.2008.108027	Respiratory System
Surfactant proteins SP-A and SP-D: Structure, function and receptors. Surfactant proteins. SP-A and SP-D, are collagen-containing C-type (calcium dependent) lectins called collectins, which contribute significantly to surfactant homeostasis and pulmonary immunity. These highly versatile innate immune molecules are involved in a range of immune functions including viral neutralization. clearance of bacteria, fungi and apoptotic and necrotic cells, down regulation of allergic reaction and resolution of inflammation. Their basic structures include a triple-helical collagen region and a C-terminal homotrimeric lectin or carbohydrate recognition domain (CRD). The trimeric CRDs can recognize carbohydrate or charge patterns on microbes, allergens and dying cells, while the collagen region can interact with receptor molecules present on a variety of immune cells in order to initiate clearance mechanisms. Studies involving gene knock-out mice. murine models of lung hypersensitivity and infection, and functional characterization of cell surface receptors have revealed the diverse roles of SP-A and SP-D in the control of lung inflammation. A recently proposed model based on studies with the calreticulin-CD91 complex as a receptor for SP-A and SP-D has suggested an anti-inflammatory role for SP-A and SP-D in naive lungs which would help minimise the potential damage that continual low level exposure to pathogens, allergens and apoptosis can cause. However, when the lungs are overwhelmed with exogenous insults, SP-A and SP-D can assume pro-inflammatory roles in order to complement pulmonary innate and adaptive immunity. This review is an update on the structural and functional aspects of SP-A and SP-D, with emphasis on their roles in controlling pulmonary infection, allergy and inflammation. We also try to put in perspective the controversial subject of the candidate receptor molecules for SP-A and SP-D. (c) 2005 Elsevier Ltd. All rights reserved.. surfactant| immunity| lung| allergy| infection| crystal structure|respiratory syncytial virus| gene-targeted mice| carbohydrate-recognition domains| gram-negative bacteria| human amniotic-fluid| eosinophilic airway inflammation| hepatocyte nuclear factor-3-beta| mediates enhanced phagocytosis| colony-stimulating factor| mannan-binding protein.	MAR-2006	surfactant| immunity| lung| allergy| infection| crystal structure|respiratory syncytial virus| gene-targeted mice| carbohydrate-recognition domains| gram-negative bacteria| human amniotic-fluid| eosinophilic airway inflammation| hepatocyte nuclear factor-3-beta| mediates enhanced phagocytosis| colony-stimulating factor| mannan-binding protein	Kishore, U; Greenhough, TJ; Waters, P; Shrive, AK; Ghai, R; Kamran, MF; Bernal, AL; Reid, KBM; Madan, T; Chakraborty, T	Surfactant proteins SP-A and SP-D: Structure, function and receptors		MOLECULAR IMMUNOLOGY	surfactant; immunity; lung; allergy; infection; crystal structure	RESPIRATORY SYNCYTIAL VIRUS; GENE-TARGETED MICE; CARBOHYDRATE-RECOGNITION DOMAINS; GRAM-NEGATIVE BACTERIA; HUMAN AMNIOTIC-FLUID; EOSINOPHILIC AIRWAY INFLAMMATION; HEPATOCYTE NUCLEAR FACTOR-3-BETA; MEDIATES ENHANCED PHAGOCYTOSIS; COLONY-STIMULATING FACTOR; MANNAN-BINDING PROTEIN	Surfactant proteins. SP-A and SP-D, are collagen-containing C-type (calcium dependent) lectins called collectins, which contribute significantly to surfactant homeostasis and pulmonary immunity. These highly versatile innate immune molecules are involved in a range of immune functions including viral neutralization. clearance of bacteria, fungi and apoptotic and necrotic cells, down regulation of allergic reaction and resolution of inflammation. Their basic structures include a triple-helical collagen region and a C-terminal homotrimeric lectin or carbohydrate recognition domain (CRD). The trimeric CRDs can recognize carbohydrate or charge patterns on microbes, allergens and dying cells, while the collagen region can interact with receptor molecules present on a variety of immune cells in order to initiate clearance mechanisms. Studies involving gene knock-out mice. murine models of lung hypersensitivity and infection, and functional characterization of cell surface receptors have revealed the diverse roles of SP-A and SP-D in the control of lung inflammation. A recently proposed model based on studies with the calreticulin-CD91 complex as a receptor for SP-A and SP-D has suggested an anti-inflammatory role for SP-A and SP-D in naive lungs which would help minimise the potential damage that continual low level exposure to pathogens, allergens and apoptosis can cause. However, when the lungs are overwhelmed with exogenous insults, SP-A and SP-D can assume pro-inflammatory roles in order to complement pulmonary innate and adaptive immunity. This review is an update on the structural and functional aspects of SP-A and SP-D, with emphasis on their roles in controlling pulmonary infection, allergy and inflammation. We also try to put in perspective the controversial subject of the candidate receptor molecules for SP-A and SP-D. (c) 2005 Elsevier Ltd. All rights reserved.	194	245	2006	23	10.1016/j.molimm.2005.08.004	Biochemistry & Molecular Biology; Immunology
High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. The aim of this prospective study was to determine the prevalence and characteristics of acid gastro-oesophageal reflux (GER) in patients with idiopathic pulmonary fibrosis (IPF). Sixty-five consecutive patients with well-defined IPF were subjected to 24-h pH monitoring and oesophageal manometry. A total of 133 consecutive patients with intractable asthma and symptoms of GER were used as comparisons. The prevalence of abnormal acid GER in IPF patients was 87%, with 76% and 63% demonstrating abnormal distal and proximal oesophageal acid exposures, respectively. Abnormal acid GER was significantly more common in IPF patients than asthma patients. Only 47% of IPF patients experienced classic GER symptoms. Despite treatment with standard doses of proton pump inhibitors (PPIs), 12 out of 19 patients receiving PPIs during the 24-h pH monitoring had abnormal oesophageal acid exposures by pH probe. There was no correlation between IPF severity and acid GER severity. In conclusion, abnormal acid gastro-oesophageal reflux is highly prevalent, but often clinically occult in patients with idiopathic pulmonary fibrosis. Standard doses of proton pump inhibitors may not suppress the acid gastro-oesophageal reflux in this population. Therefore, further studies are needed to determine if acid abnormal gastro-oesophageal reflux represents an important risk factor for idiopathic pulmonary fibrosis development or progression, and if optimal suppression of acid gastro-oesophageal reflux slows the progression of idiopathic pulmonary fibrosis and/or decreases episodic exacerbations of idiopathic pulmonary fibrosis.. aspiration| cryptogenic fibrosing alveolitis| gastro-oesophageal reflux disease| idiopathic pulmonary fibrosis| usual interstitial pneumonia|surgical therapy| hiatal hernia| disease| aspiration| frequency| pressure| asthma.	JAN-2006	aspiration| cryptogenic fibrosing alveolitis| gastro-oesophageal reflux disease| idiopathic pulmonary fibrosis| usual interstitial pneumonia|surgical therapy| hiatal hernia| disease| aspiration| frequency| pressure| asthma	Raghu, G; Freudenberger, TD; Yang, S; Curtis, JR; Spada, C; Hayes, J; Sillery, JK; Pope, CE; Pellegrini, CA	High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis		EUROPEAN RESPIRATORY JOURNAL	aspiration; cryptogenic fibrosing alveolitis; gastro-oesophageal reflux disease; idiopathic pulmonary fibrosis; usual interstitial pneumonia	SURGICAL THERAPY; HIATAL HERNIA; DISEASE; ASPIRATION; FREQUENCY; PRESSURE; ASTHMA	The aim of this prospective study was to determine the prevalence and characteristics of acid gastro-oesophageal reflux (GER) in patients with idiopathic pulmonary fibrosis (IPF). Sixty-five consecutive patients with well-defined IPF were subjected to 24-h pH monitoring and oesophageal manometry. A total of 133 consecutive patients with intractable asthma and symptoms of GER were used as comparisons. The prevalence of abnormal acid GER in IPF patients was 87%, with 76% and 63% demonstrating abnormal distal and proximal oesophageal acid exposures, respectively. Abnormal acid GER was significantly more common in IPF patients than asthma patients. Only 47% of IPF patients experienced classic GER symptoms. Despite treatment with standard doses of proton pump inhibitors (PPIs), 12 out of 19 patients receiving PPIs during the 24-h pH monitoring had abnormal oesophageal acid exposures by pH probe. There was no correlation between IPF severity and acid GER severity. In conclusion, abnormal acid gastro-oesophageal reflux is highly prevalent, but often clinically occult in patients with idiopathic pulmonary fibrosis. Standard doses of proton pump inhibitors may not suppress the acid gastro-oesophageal reflux in this population. Therefore, further studies are needed to determine if acid abnormal gastro-oesophageal reflux represents an important risk factor for idiopathic pulmonary fibrosis development or progression, and if optimal suppression of acid gastro-oesophageal reflux slows the progression of idiopathic pulmonary fibrosis and/or decreases episodic exacerbations of idiopathic pulmonary fibrosis.	30	245	2006	7	10.1183/09031936.06.00037005	Respiratory System
Meta-analyses of the associations of respiratory health effects with dampness and mold in homes. The Institute of Medicine (TOM) of the National Academy of Sciences recently completed a critical review of the scientific literature pertaining to the association of indoor dampness and mold contamination with adverse health effects. In this paper, we report the results of quantitative meta-analyses of the studies reviewed in the TOM report plus other related studies. We developed point estimates and confidence intervals (CIs) of odds ratios (ORs) that summarize the association of several respiratory and asthma-related health outcomes with the presence of dampness and mold in homes. The ORs and CIs from the original studies were transformed to the log scale and random effect models were applied to the log ORs and their variance. Models accounted for the correlation between multiple results within the studies analyzed. Central estimates of ORs for the health outcomes ranged from 1.34 to 1.75. CIs (95%) excluded unity in nine of 10 instances, and in most cases the lower bound of the CI exceeded 1.2. Based on the results of the meta-analyses, building dampness and mold are associated with approximately 30-50% increases in a variety of respiratory and asthma-related health outcomes.. primary-school children| adult-onset asthma| indoor environment| building dampness| risk-factors| preschool-children| childhood asthma| parental atopy| symptoms| exposures.	AUG-2007	primary-school children| adult-onset asthma| indoor environment| building dampness| risk-factors| preschool-children| childhood asthma| parental atopy| symptoms| exposures	Fisk, WJ; Lei-Gomez, Q; Mendell, MJ	Meta-analyses of the associations of respiratory health effects with dampness and mold in homes		INDOOR AIR		PRIMARY-SCHOOL CHILDREN; ADULT-ONSET ASTHMA; INDOOR ENVIRONMENT; BUILDING DAMPNESS; RISK-FACTORS; PRESCHOOL-CHILDREN; CHILDHOOD ASTHMA; PARENTAL ATOPY; SYMPTOMS; EXPOSURES	The Institute of Medicine (TOM) of the National Academy of Sciences recently completed a critical review of the scientific literature pertaining to the association of indoor dampness and mold contamination with adverse health effects. In this paper, we report the results of quantitative meta-analyses of the studies reviewed in the TOM report plus other related studies. We developed point estimates and confidence intervals (CIs) of odds ratios (ORs) that summarize the association of several respiratory and asthma-related health outcomes with the presence of dampness and mold in homes. The ORs and CIs from the original studies were transformed to the log scale and random effect models were applied to the log ORs and their variance. Models accounted for the correlation between multiple results within the studies analyzed. Central estimates of ORs for the health outcomes ranged from 1.34 to 1.75. CIs (95%) excluded unity in nine of 10 instances, and in most cases the lower bound of the CI exceeded 1.2. Based on the results of the meta-analyses, building dampness and mold are associated with approximately 30-50% increases in a variety of respiratory and asthma-related health outcomes.	41	244	2007	13	10.1111/j.1600-0668.2007.00475.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey. Objective To assess whether the.. severity of asthma is associated with sensitisation to airborne moulds rather than to other seasonal or perennial allergens. Design Multicentre epidemiological survey in 30 centres. Setting European Community respiratory health survey. Participants 1132 adults. aged 20-44 years with current asthma and with skin prick test results. Main outcome measure Severity of asthma according to score based on forced expiratory volume in one second, number of asthma attacks, hospital admissions for breathing problems, and use of corticosteroids in past 12 months. Results The frequency of sensitisation to moulds (Alternaria alternata or Cladosporium herbarum, or both) increased significantly with increasing asthma severity (odds ratio 2.34 (95% confidence interval 1.56 to 3.52) for either for severe v mild asthma). This association existed in all of the study areas (gathered into regions), although there were differences in the frequency of sensitisation. There was no association between asthma severity and sensitisation to pollens or cats. Sensitisation to Dermatophagoides pteronyssinus was also positively associated with severity. In multivariable logistic regressions including sensitisation to moulds, pollens, D pteronyssinus, and cats simultaneously, the odds ratios for sensitisation to moulds were 1.48 (0.97 to 2.26) for moderate v mild asthma and 2.16 (1.37 to 3.35) for severe v mild asthma (P < 0.001 for trend)., Conclusions Sensitisation to moulds is a powerful risk factor for severe asthma in adults. This should be taken into account in primary prevention, management and patients' education.. skin-test reactivity| young-adults| risk factor| individual allergens| lung-function| children| association| symptoms| exposure| sensitization.	AUG 24-2002	skin-test reactivity| young-adults| risk factor| individual allergens| lung-function| children| association| symptoms| exposure| sensitization	Zureik, M; Neukirch, C; Leynaert, B; Liard, R; Bousquet, L; Neukirch, F	Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey		BRITISH MEDICAL JOURNAL		SKIN-TEST REACTIVITY; YOUNG-ADULTS; RISK FACTOR; INDIVIDUAL ALLERGENS; LUNG-FUNCTION; CHILDREN; ASSOCIATION; SYMPTOMS; EXPOSURE; SENSITIZATION	Objective To assess whether the.. severity of asthma is associated with sensitisation to airborne moulds rather than to other seasonal or perennial allergens. Design Multicentre epidemiological survey in 30 centres. Setting European Community respiratory health survey. Participants 1132 adults. aged 20-44 years with current asthma and with skin prick test results. Main outcome measure Severity of asthma according to score based on forced expiratory volume in one second, number of asthma attacks, hospital admissions for breathing problems, and use of corticosteroids in past 12 months. Results The frequency of sensitisation to moulds (Alternaria alternata or Cladosporium herbarum, or both) increased significantly with increasing asthma severity (odds ratio 2.34 (95% confidence interval 1.56 to 3.52) for either for severe v mild asthma). This association existed in all of the study areas (gathered into regions), although there were differences in the frequency of sensitisation. There was no association between asthma severity and sensitisation to pollens or cats. Sensitisation to Dermatophagoides pteronyssinus was also positively associated with severity. In multivariable logistic regressions including sensitisation to moulds, pollens, D pteronyssinus, and cats simultaneously, the odds ratios for sensitisation to moulds were 1.48 (0.97 to 2.26) for moderate v mild asthma and 2.16 (1.37 to 3.35) for severe v mild asthma (P < 0.001 for trend)., Conclusions Sensitisation to moulds is a powerful risk factor for severe asthma in adults. This should be taken into account in primary prevention, management and patients' education.	33	244	2002	6	10.1136/bmj.325.7361.411	General & Internal Medicine
Vaccination with genetically engineered allergens prevents progression of allergic disease. IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.. birch pollen allergen| b-cell epitopes| hay-fever| v 1| immunotherapy| ige| gene| derivatives| candidates| responses.	OCT 5-2004	birch pollen allergen| b-cell epitopes| hay-fever| v 1| immunotherapy| ige| gene| derivatives| candidates| responses	Niederberger, V; Horak, F; Vrtala, S; Spitzauer, S; Krauth, MT; Valent, P; Reisinger, J; Pelzmann, M; Hayek, B; Kronqvist, M; Gafvelin, G; Gronlund, H; Purohit, A; Suck, R; Fiebig, H; Cromwell, O; Pauli, G; van Hage-Hamsten, M; Valenta, R	Vaccination with genetically engineered allergens prevents progression of allergic disease		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA		BIRCH POLLEN ALLERGEN; B-CELL EPITOPES; HAY-FEVER; V 1; IMMUNOTHERAPY; IGE; GENE; DERIVATIVES; CANDIDATES; RESPONSES	IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients (n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.	31	243	2004	6	10.1073/pnas.0404735101	Science & Technology - Other Topics
A Randomized, Double-blind, Placebo-controlled Study of Tumor Necrosis Factor-alpha Blockade in Severe Persistent Asthma. Rationale: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown. Objectives: To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma. Methods: From 2004 to 2006, 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting beta(2) agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1) and the number of severe asthma exacerbations through Week 24. Measurements and Main Results: No significant differences were observed for the change in percent-predicted FEV(1) (least squares mean: placebo, 2.44 [95% confidence interval (CI) -0.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696-5.116]) or severe exacerbations (mean +/- SD: placebo, 0.5 +/- 1.07 vs. combined 100-mg and 200-mg 0.5 +/- 0.97) through week 24. Through Week 24, 2.6% of patients treated with placebo vs. 19.5% of those treated with golimumab discontinued the study agent, and 1.3% and 7.8% discontinued study participation, respectively. An unfavorable risk-benefit profile led to early discontinuation of study-agent administration after the Week-24 database lock. Through Week 76, 20.5% of patients treated with placebo and 30.3% of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients. One death and all eight malignancies occurred in the active groups. Conclusions Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients. golimumab| asthma| tumor necrosis factor-alpha|air-flow limitation| smooth-muscle| tnf-alpha| clinical characteristics| rheumatoid-arthritis| monoclonal-antibody| refractory asthma| bronchial-asthma| cancer incidence| risk-factors.	APR 1-2009	golimumab| asthma| tumor necrosis factor-alpha|air-flow limitation| smooth-muscle| tnf-alpha| clinical characteristics| rheumatoid-arthritis| monoclonal-antibody| refractory asthma| bronchial-asthma| cancer incidence| risk-factors	Wenzel, SE; Barnes, PJ; Bleecker, ER; Bousquet, J; Busse, W; Dahlen, SE; Holgate, ST; Meyers, DA; Rabe, KF; Antczak, A; Baker, J; Horvath, I; Mark, Z; Bernstein, D; Kerwin, E; Schlenker-Herceg, R; Lo, KH; Watt, R; Barnathan, ES; Chanez, P	A Randomized, Double-blind, Placebo-controlled Study of Tumor Necrosis Factor-alpha Blockade in Severe Persistent Asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	golimumab; asthma; tumor necrosis factor-alpha	AIR-FLOW LIMITATION; SMOOTH-MUSCLE; TNF-ALPHA; CLINICAL CHARACTERISTICS; RHEUMATOID-ARTHRITIS; MONOCLONAL-ANTIBODY; REFRACTORY ASTHMA; BRONCHIAL-ASTHMA; CANCER INCIDENCE; RISK-FACTORS	Rationale: The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown. Objectives: To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma. Methods: From 2004 to 2006, 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting beta(2) agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1) and the number of severe asthma exacerbations through Week 24. Measurements and Main Results: No significant differences were observed for the change in percent-predicted FEV(1) (least squares mean: placebo, 2.44 [95% confidence interval (CI) -0.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696-5.116]) or severe exacerbations (mean +/- SD: placebo, 0.5 +/- 1.07 vs. combined 100-mg and 200-mg 0.5 +/- 0.97) through week 24. Through Week 24, 2.6% of patients treated with placebo vs. 19.5% of those treated with golimumab discontinued the study agent, and 1.3% and 7.8% discontinued study participation, respectively. An unfavorable risk-benefit profile led to early discontinuation of study-agent administration after the Week-24 database lock. Through Week 76, 20.5% of patients treated with placebo and 30.3% of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients. One death and all eight malignancies occurred in the active groups. Conclusions Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients	52	241	2009	10	10.1164/rccm.200809-1512OC	General & Internal Medicine; Respiratory System
Egg oral immunotherapy in nonanaphylactic children with egg allergy. Background: There is no current active treatment for food allergy. Traditional injection immunotherapy has been proved unsafe, and thus there is a need for other forms of immunotherapy. Objective: The purpose was to study the safety and immunologic effects of egg oral immunotherapy (OIT). The short-term goal was to desensitize subjects to protect against accidental ingestion reactions. The eventual goal was to induce lasting clinical and immunologic tolerance. Methods: Subjects with a history of egg allergy but without a history of anaphylaxis to egg underwent a 24-month egg OIT protocol involving modified rush, build-up, and maintenance phases. Double-blind, placebo-controlled food challenges were performed at study conclusion. Egg-specific IgE and IgG concentrations were followed. Results: Seven subjects completed the protocol. Egg-specific IgG concentrations increased significantly, whereas egg-specific IgE concentrations did not significantly change. Three subjects tolerated known or possible accidental egg ingestions while receiving OIT. During double-blind, placebo-controlled food challenges at study conclusion, all tolerated significantly more egg protein than at study onset and than that found in the typical accidental exposure. Two subjects demonstrated oral tolerance. Conclusion: This study provides proof of concept that OIT can be safely used for patients with egg allergy without a history of anaphylaxis to egg. Egg OIT does not heighten sensitivity to egg and might protect against reaction on accidental ingestion. Whether OIT will induce clinical oral tolerance cannot be concluded from this initial cohort. Clinical implications: Use of allergen-specific OIT to protect subjects with food allergy from reaction on accidental ingestion would represent a significant paradigm change in the treatment of food allergy.. egg allergy| food allergy| anaphylaxis| allergen immunotherapy| oral immunotherapy|quality-of-life| food allergy| peanut allergy| tolerance| families| parents| future| impact.	JAN-2007	egg allergy| food allergy| anaphylaxis| allergen immunotherapy| oral immunotherapy|quality-of-life| food allergy| peanut allergy| tolerance| families| parents| future| impact	Buchanan, AD; Green, TD; Jones, SM; Scurlock, AM; Christie, L; Althage, KA; Steele, PH; Pons, L; Heim, RM; Lee, LA; Burks, AW	Egg oral immunotherapy in nonanaphylactic children with egg allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	egg allergy; food allergy; anaphylaxis; allergen immunotherapy; oral immunotherapy	QUALITY-OF-LIFE; FOOD ALLERGY; PEANUT ALLERGY; TOLERANCE; FAMILIES; PARENTS; FUTURE; IMPACT	Background: There is no current active treatment for food allergy. Traditional injection immunotherapy has been proved unsafe, and thus there is a need for other forms of immunotherapy. Objective: The purpose was to study the safety and immunologic effects of egg oral immunotherapy (OIT). The short-term goal was to desensitize subjects to protect against accidental ingestion reactions. The eventual goal was to induce lasting clinical and immunologic tolerance. Methods: Subjects with a history of egg allergy but without a history of anaphylaxis to egg underwent a 24-month egg OIT protocol involving modified rush, build-up, and maintenance phases. Double-blind, placebo-controlled food challenges were performed at study conclusion. Egg-specific IgE and IgG concentrations were followed. Results: Seven subjects completed the protocol. Egg-specific IgG concentrations increased significantly, whereas egg-specific IgE concentrations did not significantly change. Three subjects tolerated known or possible accidental egg ingestions while receiving OIT. During double-blind, placebo-controlled food challenges at study conclusion, all tolerated significantly more egg protein than at study onset and than that found in the typical accidental exposure. Two subjects demonstrated oral tolerance. Conclusion: This study provides proof of concept that OIT can be safely used for patients with egg allergy without a history of anaphylaxis to egg. Egg OIT does not heighten sensitivity to egg and might protect against reaction on accidental ingestion. Whether OIT will induce clinical oral tolerance cannot be concluded from this initial cohort. Clinical implications: Use of allergen-specific OIT to protect subjects with food allergy from reaction on accidental ingestion would represent a significant paradigm change in the treatment of food allergy.	35	241	2007	7	10.1016/j.jaci.2006.09.016	Allergy; Immunology
Rhinitis and asthma: Evidence for respiratory system integration. The vast majority of patients with asthma have rhinitis, and rhinitis is a major independent risk factor for asthma in cross-sectional and longitudinal studies. The relationships between rhinitis and asthma can be viewed under the concept that the 2 conditions are manifestations of one syndrome, the chronic allergic respiratory syndrome, in 2 parts of the respiratory tract. At the low end of the syndrome's severity spectrum, rhinitis appears to be the sole manifestation, although pathologic abnormalities in the lower airways are already present. At the higher end, rhinitis is worse, and the lower airways disease becomes clinically evident. Once manifested, the 2 conditions track in parallel in terms of severity. This parallel relationship is influenced by many interactions between the nasal and the lower airways: some interactions stem from the fact that the nasal passages play a major homeostatic role by conditioning inhaled air, but perhaps even more important is the bidirectional interaction that results from the systemic inflammation that is produced after local allergic reactions. Successful management of the chronic allergic respiratory syndrome requires an integrated view of the airways and an understanding of their interactions.. allergy| nasal function| lung function| rhinitis epidemiology| asthma epidemiology|skin-test reactivity| nitric-oxide synthase| perennial allergic rhinitis| colony-stimulating factor| messenger-rna expression| independent risk factor| serum ige levels| bronchial responsiveness| nasal-mucosa| mast-cell.	JUN-2003	allergy| nasal function| lung function| rhinitis epidemiology| asthma epidemiology|skin-test reactivity| nitric-oxide synthase| perennial allergic rhinitis| colony-stimulating factor| messenger-rna expression| independent risk factor| serum ige levels| bronchial responsiveness| nasal-mucosa| mast-cell	Togias, A	Rhinitis and asthma: Evidence for respiratory system integration		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; nasal function; lung function; rhinitis epidemiology; asthma epidemiology	SKIN-TEST REACTIVITY; NITRIC-OXIDE SYNTHASE; PERENNIAL ALLERGIC RHINITIS; COLONY-STIMULATING FACTOR; MESSENGER-RNA EXPRESSION; INDEPENDENT RISK FACTOR; SERUM IGE LEVELS; BRONCHIAL RESPONSIVENESS; NASAL-MUCOSA; MAST-CELL	The vast majority of patients with asthma have rhinitis, and rhinitis is a major independent risk factor for asthma in cross-sectional and longitudinal studies. The relationships between rhinitis and asthma can be viewed under the concept that the 2 conditions are manifestations of one syndrome, the chronic allergic respiratory syndrome, in 2 parts of the respiratory tract. At the low end of the syndrome's severity spectrum, rhinitis appears to be the sole manifestation, although pathologic abnormalities in the lower airways are already present. At the higher end, rhinitis is worse, and the lower airways disease becomes clinically evident. Once manifested, the 2 conditions track in parallel in terms of severity. This parallel relationship is influenced by many interactions between the nasal and the lower airways: some interactions stem from the fact that the nasal passages play a major homeostatic role by conditioning inhaled air, but perhaps even more important is the bidirectional interaction that results from the systemic inflammation that is produced after local allergic reactions. Successful management of the chronic allergic respiratory syndrome requires an integrated view of the airways and an understanding of their interactions.	142	241	2003	13	10.1067/mai.2003.1592	Allergy; Immunology
Changes in sputum eosinophils predict less of asthma control. Exacerbations of asthma are likely to be due to an increase in airway inflammation. We have studied noninvasive markers of airway inflammation in asthma exacerbations induced by reducing the dose of inhaled corticosteroids. Following a 2-wk run-in period, mild exacerbations were induced in subjects with stable asthma controlled with medium- to high-dose inhaled corticosteroids (beclomethasone dipropionate greater than or equal to 800 mu g or equivalent daily) by switching them to budesonide 200 mu g daily given from a dry-powder inhaler (Turbohaler). Fifteen subjects were enrolled and were seen twice weekly for 8 wk after steroid reduction. At each visit, exhaled nitric oxide (NO), and methacholine airway responsiveness were measured and spirometry and sputum induction were performed. Mild exacerbation was defined as: (1) a decrease in morning peak expiratory flow (PEF) of greater than or equal to 20% but < 30% on at least two consecutive days as compared with the mean for the last 7 d of the run-in period; (2) awakening on two consecutive nights because of asthma; or (3) increased use of a short-acting beta(2)-agonist to eight or more puffs daily. Eight subjects did not develop exacerbations during the 8-wk study, whereas seven subjects developed mild exacerbations at Week 4 (n = 1), Week 6 (n = 1), and Week 8 (n = 5). The only significant difference between these two groups at baseline was a higher baseline sputum eosinophil count in subjects with subsequent exacerbations (p < 0.05). The increases in sputum eosinophils and exhaled NO were correlated with decreases in airway function, including decreases in morning PEF and FEV1. However, multiple regression analysis suggested that the change in sputum eosinophils is a potentially useful marker in predicting loss of asthma control reflected by loss of airway function.. exhaled nitric-oxide| airway inflammation| respiratory-tract| mild asthma| exacerbations| glucocorticoids| prednisone| budesonide| exposure| examine.	JAN-2000	exhaled nitric-oxide| airway inflammation| respiratory-tract| mild asthma| exacerbations| glucocorticoids| prednisone| budesonide| exposure| examine	Jatakanon, A; Lim, S; Barnes, PJ	Changes in sputum eosinophils predict less of asthma control		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		EXHALED NITRIC-OXIDE; AIRWAY INFLAMMATION; RESPIRATORY-TRACT; MILD ASTHMA; EXACERBATIONS; GLUCOCORTICOIDS; PREDNISONE; BUDESONIDE; EXPOSURE; EXAMINE	Exacerbations of asthma are likely to be due to an increase in airway inflammation. We have studied noninvasive markers of airway inflammation in asthma exacerbations induced by reducing the dose of inhaled corticosteroids. Following a 2-wk run-in period, mild exacerbations were induced in subjects with stable asthma controlled with medium- to high-dose inhaled corticosteroids (beclomethasone dipropionate greater than or equal to 800 mu g or equivalent daily) by switching them to budesonide 200 mu g daily given from a dry-powder inhaler (Turbohaler). Fifteen subjects were enrolled and were seen twice weekly for 8 wk after steroid reduction. At each visit, exhaled nitric oxide (NO), and methacholine airway responsiveness were measured and spirometry and sputum induction were performed. Mild exacerbation was defined as: (1) a decrease in morning peak expiratory flow (PEF) of greater than or equal to 20% but < 30% on at least two consecutive days as compared with the mean for the last 7 d of the run-in period; (2) awakening on two consecutive nights because of asthma; or (3) increased use of a short-acting beta(2)-agonist to eight or more puffs daily. Eight subjects did not develop exacerbations during the 8-wk study, whereas seven subjects developed mild exacerbations at Week 4 (n = 1), Week 6 (n = 1), and Week 8 (n = 5). The only significant difference between these two groups at baseline was a higher baseline sputum eosinophil count in subjects with subsequent exacerbations (p < 0.05). The increases in sputum eosinophils and exhaled NO were correlated with decreases in airway function, including decreases in morning PEF and FEV1. However, multiple regression analysis suggested that the change in sputum eosinophils is a potentially useful marker in predicting loss of asthma control reflected by loss of airway function.	32	240	2000	9		General & Internal Medicine; Respiratory System
In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure. High dose bee venom exposure in beekeepers by natural bee stings represents a model to understand mechanisms of T cell tolerance to allergens in healthy individuals. Continuous exposure of nonallergic beekeepers to high doses of bee venom antigens induces diminished T cell-related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion. After multiple bee stings, venom antigen-specific Th1 and Th2 cells show a switch toward interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells. T cell regulation continues as long as antigen exposure persists and returns to initial levels within 2 to 3 mo after bee stings. Histamine receptor 2 up-regulated on specific Th2 cells displays a dual effect by directly suppressing allergen-stimulated T cells and increasing IL-10 production. In addition, cytotoxic T lymphocyte-associated antigen 4 and programmed death 1 play roles in allergen-specific T cell suppression. In contrast to its role in mucosal allergen tolerance, transforming growth factor beta does not seem to be an essential player in skin-related allergen tolerance. Thus, rapid switch and expansion of IL-10-producing Tr1 cells and the use of multiple suppressive factors represent essential mechanisms in immune tolerance to a high dose of allergens in nonallergic individuals.. phase cutaneous reactions| bee venom| autoimmune-diseases| immune-responses| gene-expression| dendritic cells| atopic subjects| self-tolerance| oral tolerance| il-10 receptor.	NOV 24-2008	phase cutaneous reactions| bee venom| autoimmune-diseases| immune-responses| gene-expression| dendritic cells| atopic subjects| self-tolerance| oral tolerance| il-10 receptor	Meiler, F; Zumkehr, J; Klunker, S; Ruckert, B; Akdis, CA; Akdis, M	In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure		JOURNAL OF EXPERIMENTAL MEDICINE		PHASE CUTANEOUS REACTIONS; BEE VENOM; AUTOIMMUNE-DISEASES; IMMUNE-RESPONSES; GENE-EXPRESSION; DENDRITIC CELLS; ATOPIC SUBJECTS; SELF-TOLERANCE; ORAL TOLERANCE; IL-10 RECEPTOR	High dose bee venom exposure in beekeepers by natural bee stings represents a model to understand mechanisms of T cell tolerance to allergens in healthy individuals. Continuous exposure of nonallergic beekeepers to high doses of bee venom antigens induces diminished T cell-related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion. After multiple bee stings, venom antigen-specific Th1 and Th2 cells show a switch toward interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells. T cell regulation continues as long as antigen exposure persists and returns to initial levels within 2 to 3 mo after bee stings. Histamine receptor 2 up-regulated on specific Th2 cells displays a dual effect by directly suppressing allergen-stimulated T cells and increasing IL-10 production. In addition, cytotoxic T lymphocyte-associated antigen 4 and programmed death 1 play roles in allergen-specific T cell suppression. In contrast to its role in mucosal allergen tolerance, transforming growth factor beta does not seem to be an essential player in skin-related allergen tolerance. Thus, rapid switch and expansion of IL-10-producing Tr1 cells and the use of multiple suppressive factors represent essential mechanisms in immune tolerance to a high dose of allergens in nonallergic individuals.	52	239	2008	18	10.1084/jem.20080193	Immunology; Research & Experimental Medicine
Probiotics in prevention of IgE-associated eczema: A double-blind, randomized, placebo-controlled trial. Background: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants. Objective: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri. Methods: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730(1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Results: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected. Conclusion: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. Clinical implication: Probiotics may reduce the incidence of IgE-associated eczema in infancy.. children| eczema| ige| lactobacillus| prevention| probiotics| sensitization| skin prick test|atopic-dermatitis| lactobacillus-reuteri| in-vitro| children| infants| disease| colonization| supplementation| sensitization| infections.	MAY-2007	children| eczema| ige| lactobacillus| prevention| probiotics| sensitization| skin prick test|atopic-dermatitis| lactobacillus-reuteri| in-vitro| children| infants| disease| colonization| supplementation| sensitization| infections	Abrahamsson, TR; Jakobsson, T; Bottcher, MF; Fredrikson, M; Jenmalm, MC; Bjorksten, B; Oldaeus, G	Probiotics in prevention of IgE-associated eczema: A double-blind, randomized, placebo-controlled trial		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	children; eczema; IgE; Lactobacillus; prevention; probiotics; sensitization; skin prick test	ATOPIC-DERMATITIS; LACTOBACILLUS-REUTERI; IN-VITRO; CHILDREN; INFANTS; DISEASE; COLONIZATION; SUPPLEMENTATION; SENSITIZATION; INFECTIONS	Background: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants. Objective: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri. Methods: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730(1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Results: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected. Conclusion: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. Clinical implication: Probiotics may reduce the incidence of IgE-associated eczema in infancy.	35	239	2007	7	10.1016/j.jaci.2007.01.007	Allergy; Immunology
Inhibition of experimental asthma by indoleamine 2,3-dioxygenase. Epidemiological evidence points to the inverse relationship between microbial exposure and the prevalence of allergic asthma and autoimmune diseases in Westernized countries. The molecular basis for this observation has not yet been completely delineated. Here we report that the administration of certain toll-like receptor (TLR) ligands, via the activation of innate immunity, induces high levels of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism in various organs. TLR9 ligand-induced pulmonary IDO activity inhibits Th2-driven experimental asthma. IDO activity expressed by resident lung cells rather than by pulmonary DCs suppressed lung inflammation and airway hyperreactivity. Our results provide a mechanistic insight into the various formulations of the hygiene hypothesis and underscore the notion that activation of innate immunity can inhibit adaptive Th cell responses.. t-cell proliferation| dendritic cells| immunostimulatory dna| tryptophan catabolism| hygiene hypothesis| in-vivo| airway inflammation| allergic diseases| epithelial-cells| interferon-gamma.	JUL-2004	t-cell proliferation| dendritic cells| immunostimulatory dna| tryptophan catabolism| hygiene hypothesis| in-vivo| airway inflammation| allergic diseases| epithelial-cells| interferon-gamma	Hayashi, T; Beck, L; Rossetto, C; Gong, X; Takikawa, O; Takabayashi, K; Broide, DH; Carson, DA; Raz, E	Inhibition of experimental asthma by indoleamine 2,3-dioxygenase		JOURNAL OF CLINICAL INVESTIGATION		T-CELL PROLIFERATION; DENDRITIC CELLS; IMMUNOSTIMULATORY DNA; TRYPTOPHAN CATABOLISM; HYGIENE HYPOTHESIS; IN-VIVO; AIRWAY INFLAMMATION; ALLERGIC DISEASES; EPITHELIAL-CELLS; INTERFERON-GAMMA	Epidemiological evidence points to the inverse relationship between microbial exposure and the prevalence of allergic asthma and autoimmune diseases in Westernized countries. The molecular basis for this observation has not yet been completely delineated. Here we report that the administration of certain toll-like receptor (TLR) ligands, via the activation of innate immunity, induces high levels of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of tryptophan catabolism in various organs. TLR9 ligand-induced pulmonary IDO activity inhibits Th2-driven experimental asthma. IDO activity expressed by resident lung cells rather than by pulmonary DCs suppressed lung inflammation and airway hyperreactivity. Our results provide a mechanistic insight into the various formulations of the hygiene hypothesis and underscore the notion that activation of innate immunity can inhibit adaptive Th cell responses.	50	239	2004	10	10.1172/JCI200421275	Research & Experimental Medicine
The airway epithelium: Structural and functional properties in health and disease. The major function of the respiratory epithelium was once thought to be that of a physical barrier. However, it constitutes the interface between the internal milieu and the external environment as well as being a primary target for inhaled respiratory drugs. It also responds to changes in the external environment by secreting a large number of molecules and mediators that signal to cells of the immune system and underlying mesenchyme. Thus, the epithelium is in a unique position to translate gene-environment interactions. Normally, the epithelium has a tremendous capacity to repair itself following injury. However, evidence is rapidly accumulating to show that the air-way epithelium of asthmatics is abnormal and has increased susceptibility to injury compared to normal epithelium. Areas of detachment and fragility are a characteristic feature not observed in other inflammatory diseases such as COPD. In addition to being more susceptible to damage, normal repair processes are also compromised. Failure of appropriate growth and differentiation of airway epithelial cells will cause persistent mucosal injury. The response to traditional therapy such as glucocorticoids may also be compromised. However, whether the differences observed in asthmatic epithelium are a cause of or secondary to the development of the disease remains unanswered. Strategies to address this question include careful examination of the ontogeny of the disease in children and use of gene array technology should provide some important answers, as well as allow a better understanding of the critical role that the epithelium plays under normal conditions and in diseases such as asthma.. asthma| epithelium| human| inflammation| respiratory disease|epidermal-growth-factor| v beta 3| extracellular-matrix components| asthmatic bronchial epithelium| protease-activated receptors| arachidonic-acid metabolism| diesel exhaust particles| cell-adhesion receptors| nitric-oxide synthases| repair in-vivo.	DEC-2003	asthma| epithelium| human| inflammation| respiratory disease|epidermal-growth-factor| v beta 3| extracellular-matrix components| asthmatic bronchial epithelium| protease-activated receptors| arachidonic-acid metabolism| diesel exhaust particles| cell-adhesion receptors| nitric-oxide synthases| repair in-vivo	Knight, DA; Holgate, ST	The airway epithelium: Structural and functional properties in health and disease		RESPIROLOGY	asthma; epithelium; human; inflammation; respiratory disease	EPIDERMAL-GROWTH-FACTOR; V BETA 3; EXTRACELLULAR-MATRIX COMPONENTS; ASTHMATIC BRONCHIAL EPITHELIUM; PROTEASE-ACTIVATED RECEPTORS; ARACHIDONIC-ACID METABOLISM; DIESEL EXHAUST PARTICLES; CELL-ADHESION RECEPTORS; NITRIC-OXIDE SYNTHASES; REPAIR IN-VIVO	The major function of the respiratory epithelium was once thought to be that of a physical barrier. However, it constitutes the interface between the internal milieu and the external environment as well as being a primary target for inhaled respiratory drugs. It also responds to changes in the external environment by secreting a large number of molecules and mediators that signal to cells of the immune system and underlying mesenchyme. Thus, the epithelium is in a unique position to translate gene-environment interactions. Normally, the epithelium has a tremendous capacity to repair itself following injury. However, evidence is rapidly accumulating to show that the air-way epithelium of asthmatics is abnormal and has increased susceptibility to injury compared to normal epithelium. Areas of detachment and fragility are a characteristic feature not observed in other inflammatory diseases such as COPD. In addition to being more susceptible to damage, normal repair processes are also compromised. Failure of appropriate growth and differentiation of airway epithelial cells will cause persistent mucosal injury. The response to traditional therapy such as glucocorticoids may also be compromised. However, whether the differences observed in asthmatic epithelium are a cause of or secondary to the development of the disease remains unanswered. Strategies to address this question include careful examination of the ontogeny of the disease in children and use of gene array technology should provide some important answers, as well as allow a better understanding of the critical role that the epithelium plays under normal conditions and in diseases such as asthma.	180	239	2003	15	10.1046/j.1440-1843.2003.00493.x	Respiratory System
The clinical spectrum of pulmonary aspergillosis. Aspergillus is a ubiquitous fungus that causes a variety of clinical syndromes in the lung, ranging from aspergilloma in patients with lung cavities, to chronic necrotizing aspergillosis in those who are mildly immunocompromised or have chronic lung disease. Invasive pulmonary aspergillosis (IPA) is a severe and commonly fatal disease that is seen in immunocompromised patients, while allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to Aspergillus antigens that mainly affects patients with asthma. In light of the increasing risk factors leading to IPA, such as organ transplantation and immunosuppressive therapy, and recent advances in the diagnosis and treatment of Aspergillus-related lung diseases, it is essential for clinicians to be familiar with the clinical presentation, diagnostic methods, and approach to management of the spectrum of pulmonary aspergillosis.. allergic pulmonary aspergillosis| aspergillus| fungal diseases| immunocompromised host| pulmonary infection|allergic bronchopulmonary aspergillosis| bone-marrow transplantation| invasive fungal-infections| acquired-immunodeficiency-syndrome| chronic eosinophilic pneumonia| linked-immunosorbent-assay| liposomal amphotericin-b| latex agglutination-test| air crescent sign| acute-leukemia.	JUN-2002	allergic pulmonary aspergillosis| aspergillus| fungal diseases| immunocompromised host| pulmonary infection|allergic bronchopulmonary aspergillosis| bone-marrow transplantation| invasive fungal-infections| acquired-immunodeficiency-syndrome| chronic eosinophilic pneumonia| linked-immunosorbent-assay| liposomal amphotericin-b| latex agglutination-test| air crescent sign| acute-leukemia	Soubani, AO; Chandrasekar, PH	The clinical spectrum of pulmonary aspergillosis		CHEST	allergic pulmonary aspergillosis; aspergillus; fungal diseases; immunocompromised host; pulmonary infection	ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; BONE-MARROW TRANSPLANTATION; INVASIVE FUNGAL-INFECTIONS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CHRONIC EOSINOPHILIC PNEUMONIA; LINKED-IMMUNOSORBENT-ASSAY; LIPOSOMAL AMPHOTERICIN-B; LATEX AGGLUTINATION-TEST; AIR CRESCENT SIGN; ACUTE-LEUKEMIA	Aspergillus is a ubiquitous fungus that causes a variety of clinical syndromes in the lung, ranging from aspergilloma in patients with lung cavities, to chronic necrotizing aspergillosis in those who are mildly immunocompromised or have chronic lung disease. Invasive pulmonary aspergillosis (IPA) is a severe and commonly fatal disease that is seen in immunocompromised patients, while allergic bronchopulmonary aspergillosis is a hypersensitivity reaction to Aspergillus antigens that mainly affects patients with asthma. In light of the increasing risk factors leading to IPA, such as organ transplantation and immunosuppressive therapy, and recent advances in the diagnosis and treatment of Aspergillus-related lung diseases, it is essential for clinicians to be familiar with the clinical presentation, diagnostic methods, and approach to management of the spectrum of pulmonary aspergillosis.	145	239	2002	12	10.1378/chest.121.6.1988	General & Internal Medicine; Respiratory System
Ambient air pollution and respiratory emergency department visits. Background: A number of emergency department studies have corroborated findings from mortality and hospital admission studies regarding an association of ambient air pollution and respiratory outcomes. More refined assessment has been limited by study size and available air quality data. Methods: Measurements of 5 pollutants (particulate matter [PM10] ozone, nitrogen dioxide [NO2] carbon monoxide [CO], and sulfur dioxide [SO2]) were available for the entire study period (I January 1993 to 31 August 2000); detailed measurements of particulate matter were available for 25 months. We obtained data on 4 million emergency department visits from 31 hospitals in Atlanta. Visits for asthma, chronic obstructive pulmonary disease, upper respiratory infection, and pneumonia were assessed in relation to air pollutants using Poisson generalized estimating equations. Results: In single-pollutant models examining 3-day moving averages of pollutants (lags 0, 1, and 2): standard deviation increases of ozone, NO2, CO, and PM10 were associated with 1-3% increases in UR1 visits; a 2 mug/m(3) increase of PM2.5 organic carbon was associated with a 3% increase in pneumonia visits; and standard deviation increases of NO2 and CO were associated with 2-3% increases in chronic obstructive pulmonary disease visits. Positive associations persisted beyond 3 days for several of the outcomes, and over a week for asthma. Conclusions: The results of this study contribute to the evidence of an association of several correlated gaseous and particulate pollutants, including ozone, NO2, CO, PM, and organic carbon, with specific respiratory conditions.. hospital admissions| size distributions| ontario hospitals| childhood asthma| human health| time-series| room visits| new-york| atlanta| epidemiology.	MAR-2005	hospital admissions| size distributions| ontario hospitals| childhood asthma| human health| time-series| room visits| new-york| atlanta| epidemiology	Peel, JL; Tolbert, PE; Klein, M; Metzger, KB; Flanders, WD; Todd, K; Mulholland, JA; Ryan, PB; Frumkin, H	Ambient air pollution and respiratory emergency department visits		EPIDEMIOLOGY		HOSPITAL ADMISSIONS; SIZE DISTRIBUTIONS; ONTARIO HOSPITALS; CHILDHOOD ASTHMA; HUMAN HEALTH; TIME-SERIES; ROOM VISITS; NEW-YORK; ATLANTA; EPIDEMIOLOGY	Background: A number of emergency department studies have corroborated findings from mortality and hospital admission studies regarding an association of ambient air pollution and respiratory outcomes. More refined assessment has been limited by study size and available air quality data. Methods: Measurements of 5 pollutants (particulate matter [PM10] ozone, nitrogen dioxide [NO2] carbon monoxide [CO], and sulfur dioxide [SO2]) were available for the entire study period (I January 1993 to 31 August 2000); detailed measurements of particulate matter were available for 25 months. We obtained data on 4 million emergency department visits from 31 hospitals in Atlanta. Visits for asthma, chronic obstructive pulmonary disease, upper respiratory infection, and pneumonia were assessed in relation to air pollutants using Poisson generalized estimating equations. Results: In single-pollutant models examining 3-day moving averages of pollutants (lags 0, 1, and 2): standard deviation increases of ozone, NO2, CO, and PM10 were associated with 1-3% increases in UR1 visits; a 2 mug/m(3) increase of PM2.5 organic carbon was associated with a 3% increase in pneumonia visits; and standard deviation increases of NO2 and CO were associated with 2-3% increases in chronic obstructive pulmonary disease visits. Positive associations persisted beyond 3 days for several of the outcomes, and over a week for asthma. Conclusions: The results of this study contribute to the evidence of an association of several correlated gaseous and particulate pollutants, including ozone, NO2, CO, PM, and organic carbon, with specific respiratory conditions.	35	238	2005	11	10.1097/01.ede.0000152905.42113.db	Public, Environmental & Occupational Health
Does the microbiota regulate immune responses outside the gut?. Perturbations in the gastrointestinal (GI) microbiota composition that occur as a result of antibiotics and diet in 'westernized' countries are strongly associated with allergies and asthma ('hygiene hypothesis'). The microbiota ('microflora') plays a crucial role in the development of mucosal tolerance, including the airways. Significant attention has been focused on the role of the microbiota in GI development, immune adaptation and initiation of GI inflammatory diseases. This review covers the post-develop mental functions that the microbiota plays in regulating immunological tolerance to allergen exposure outside the GI tract and proposes the question: is the microbiota a major regulator of the immune system?.. chain fatty-acids| anthroposophic life-style| placebo-controlled trial| intestinal microflora| oral tolerance| candida-albicans| atopic disease| t-cells| probiotic bacteria| allergic disease.	DEC-2004	chain fatty-acids| anthroposophic life-style| placebo-controlled trial| intestinal microflora| oral tolerance| candida-albicans| atopic disease| t-cells| probiotic bacteria| allergic disease	Noverr, MC; Huffnagel, GB	Does the microbiota regulate immune responses outside the gut?		TRENDS IN MICROBIOLOGY		CHAIN FATTY-ACIDS; ANTHROPOSOPHIC LIFE-STYLE; PLACEBO-CONTROLLED TRIAL; INTESTINAL MICROFLORA; ORAL TOLERANCE; CANDIDA-ALBICANS; ATOPIC DISEASE; T-CELLS; PROBIOTIC BACTERIA; ALLERGIC DISEASE	Perturbations in the gastrointestinal (GI) microbiota composition that occur as a result of antibiotics and diet in 'westernized' countries are strongly associated with allergies and asthma ('hygiene hypothesis'). The microbiota ('microflora') plays a crucial role in the development of mucosal tolerance, including the airways. Significant attention has been focused on the role of the microbiota in GI development, immune adaptation and initiation of GI inflammatory diseases. This review covers the post-develop mental functions that the microbiota plays in regulating immunological tolerance to allergen exposure outside the GI tract and proposes the question: is the microbiota a major regulator of the immune system?.	67	238	2004	7	10.1016/j.tim.2004.10.008	Biochemistry & Molecular Biology; Microbiology
Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children. Background: Asthma exacerbation is the most common cause of hospital admission in children. A study was undertaken to investigate the importance of allergen exposure in sensitised individuals in combination with viral infections and other potentially modifiable risk factors precipitating asthma hospital admission in children. Methods: Eighty four children aged 3 - 17 years admitted to hospital over a 1 year period with an acute asthma exacerbation (AA) were matched for age and sex with two control groups: stable asthmatics (SA) and children admitted to hospital with non-respiratory conditions (IC). Risk factors were assessed by questionnaires and determination of allergen sensitisation, home allergen exposure, pollen exposure, and respiratory virus infection. Results: Several non-modifiable factors (atopy, duration of asthma) were associated with increased risk. Among the modifiable factors, pet ownership, housing characteristics, and parental smoking did not differ between the groups. Regular inhaled corticosteroid treatment was significantly less common in the AA group than in the SA group (OR 0.2, 95% CI 0.1 to 0.6; p = 0.002). A significantly higher proportion of the AA group were virus infected ( 44%) and sensitised and highly exposed to sensitising allergen (76%) compared with the SA (18% and 48%) and IC groups (17% and 28%; both p < 0.001). In a multiple conditional logistic regression ( AA v SA), allergen sensitisation and exposure or virus detection alone were no longer independently associated with hospital admission. However, the combination of virus detection and sensitisation with high allergen exposure substantially increased the risk of admission to hospital ( OR 19.4, 95% CI 3.7 to 101.5, p < 0.001). Conclusions: Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission. Strategies for preventing exacerbations will need to address these factors.. antigen bronchoprovocation| inhaled corticosteroids| viral-infections| rhinovirus-16| precipitants| emergency| city| age.	MAY-2006	antigen bronchoprovocation| inhaled corticosteroids| viral-infections| rhinovirus-16| precipitants| emergency| city| age	Murray, CS; Poletti, G; Kebadze, T; Morris, J; Woodcock, A; Johnston, SL; Custovic, A	Study of modifiable risk factors for asthma exacerbations: virus infection and allergen exposure increase the risk of asthma hospital admissions in children		THORAX		ANTIGEN BRONCHOPROVOCATION; INHALED CORTICOSTEROIDS; VIRAL-INFECTIONS; RHINOVIRUS-16; PRECIPITANTS; EMERGENCY; CITY; AGE	Background: Asthma exacerbation is the most common cause of hospital admission in children. A study was undertaken to investigate the importance of allergen exposure in sensitised individuals in combination with viral infections and other potentially modifiable risk factors precipitating asthma hospital admission in children. Methods: Eighty four children aged 3 - 17 years admitted to hospital over a 1 year period with an acute asthma exacerbation (AA) were matched for age and sex with two control groups: stable asthmatics (SA) and children admitted to hospital with non-respiratory conditions (IC). Risk factors were assessed by questionnaires and determination of allergen sensitisation, home allergen exposure, pollen exposure, and respiratory virus infection. Results: Several non-modifiable factors (atopy, duration of asthma) were associated with increased risk. Among the modifiable factors, pet ownership, housing characteristics, and parental smoking did not differ between the groups. Regular inhaled corticosteroid treatment was significantly less common in the AA group than in the SA group (OR 0.2, 95% CI 0.1 to 0.6; p = 0.002). A significantly higher proportion of the AA group were virus infected ( 44%) and sensitised and highly exposed to sensitising allergen (76%) compared with the SA (18% and 48%) and IC groups (17% and 28%; both p < 0.001). In a multiple conditional logistic regression ( AA v SA), allergen sensitisation and exposure or virus detection alone were no longer independently associated with hospital admission. However, the combination of virus detection and sensitisation with high allergen exposure substantially increased the risk of admission to hospital ( OR 19.4, 95% CI 3.7 to 101.5, p < 0.001). Conclusions: Natural virus infection and real life allergen exposure in allergic asthmatic children increase the risk of hospital admission. Strategies for preventing exacerbations will need to address these factors.	34	237	2006	7	10.1136/thx.2005.042523	Respiratory System
"Immunologic influences on allergy and theT(H)1/T(H)2 balance. T(H)2 cell-mediated immune responses against ""innocuous"" antigens play a triggering role in atopic allergy. Several epidemiologic studies have clearly shown that the reduced microbial exposure of children caused by the westernized lifestyle is responsible for the increased prevalence of allergy that has occurred in the last decades in developed countries (""hygiene hypothesis""). The immunologic changes caused by the reduced exposure to pathogenic and nonpathogenic microbes during childhood are still controversial. The initial interpretation has been a lack of shift of allergen-specific responses from the T(H)2 to the T(H)1 phenotype. This is because of reduced production of IL-12 and IFNs by cells of the natural immunity stimulated by bacterial products through their Toll-like receptors (missing immune deviation). Another interpretation emphasizes the importance of reduced activity of T-regulatory cells (reduced immune suppression). However, although there are impressive amounts of data in favor of the missing immune deviation, experimental evidence supporting the role of reduced immune suppression in explaining the increased prevalence of allergy is currently weak or even contradictory. The solution to this question is very important not only from a theoretic point of view but also because of its therapeutic implications.. t(h)1t(h)2 cells| immune deviation| treg cells| immune suppression| hygiene hypothesis|regulatory t-cells| immune-response| hygiene hypothesis| dendritic cells| th2 responses| disease| lymphocytes| asthma| children| il-10."	MAR-2004	t(h)1t(h)2 cells| immune deviation| treg cells| immune suppression| hygiene hypothesis|regulatory t-cells| immune-response| hygiene hypothesis| dendritic cells| th2 responses| disease| lymphocytes| asthma| children| il-10	Romagnani, S	Immunologic influences on allergy and theT(H)1/T(H)2 balance		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	T(H)1T(H)2 cells; immune deviation; treg cells; immune suppression; hygiene hypothesis	REGULATORY T-CELLS; IMMUNE-RESPONSE; HYGIENE HYPOTHESIS; DENDRITIC CELLS; TH2 RESPONSES; DISEASE; LYMPHOCYTES; ASTHMA; CHILDREN; IL-10	"T(H)2 cell-mediated immune responses against ""innocuous"" antigens play a triggering role in atopic allergy. Several epidemiologic studies have clearly shown that the reduced microbial exposure of children caused by the westernized lifestyle is responsible for the increased prevalence of allergy that has occurred in the last decades in developed countries (""hygiene hypothesis""). The immunologic changes caused by the reduced exposure to pathogenic and nonpathogenic microbes during childhood are still controversial. The initial interpretation has been a lack of shift of allergen-specific responses from the T(H)2 to the T(H)1 phenotype. This is because of reduced production of IL-12 and IFNs by cells of the natural immunity stimulated by bacterial products through their Toll-like receptors (missing immune deviation). Another interpretation emphasizes the importance of reduced activity of T-regulatory cells (reduced immune suppression). However, although there are impressive amounts of data in favor of the missing immune deviation, experimental evidence supporting the role of reduced immune suppression in explaining the increased prevalence of allergy is currently weak or even contradictory. The solution to this question is very important not only from a theoretic point of view but also because of its therapeutic implications."	33	237	2004	6	10.1016/j.jaci.2003.11.025	Allergy; Immunology
Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.. atopic dermatitis| children| adults| risk factors| immunopathology| diagnosis| systemic treatment| topical treatment|randomized controlled-trial| staphylococcus-aureus colonization| topical calcineurin inhibitors| pimecrolimus cream 1-percent| plasmacytoid dendritic cells| placebo-controlled trial| dust-mite allergens| regulatory t-cells| long-term efficacy| double-blind.	JUL-2006	atopic dermatitis| children| adults| risk factors| immunopathology| diagnosis| systemic treatment| topical treatment|randomized controlled-trial| staphylococcus-aureus colonization| topical calcineurin inhibitors| pimecrolimus cream 1-percent| plasmacytoid dendritic cells| placebo-controlled trial| dust-mite allergens| regulatory t-cells| long-term efficacy| double-blind	Akdis, CA; Akdis, M; Bieber, T; Bindslev-Jensen, C; Boguniewicz, M; Eigenmann, P; Hamid, Q; Kapp, A; Leung, DYM; Lipozencic, JK; Luger, TA; Muraro, A; Novak, N; Platts-Mills, TAE; Rosenwasser, L; Scheynius, A; Simons, FER; Spergel, J; Turjanmaa, K; Wahn, U; Weidinger, S; Werfel, T; Zuberbier, T	Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopic dermatitis; children; adults; risk factors; immunopathology; diagnosis; systemic treatment; topical treatment	RANDOMIZED CONTROLLED-TRIAL; STAPHYLOCOCCUS-AUREUS COLONIZATION; TOPICAL CALCINEURIN INHIBITORS; PIMECROLIMUS CREAM 1-PERCENT; PLASMACYTOID DENDRITIC CELLS; PLACEBO-CONTROLLED TRIAL; DUST-MITE ALLERGENS; REGULATORY T-CELLS; LONG-TERM EFFICACY; DOUBLE-BLIND	There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.	201	236	2006	18	10.1016/j.jaci.2006.03.045	Allergy; Immunology
Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation. Background: The immunologic mechanisms underlying sublingual immunotherapy (SLIT) are still unclear, particularly the role of regulatory T cells. Objective: We sought to characterize allergen-specific T-cell responses during successful birch pollen SLIT. Methods: Proliferation of PBMCs and PBMCs depleted of CD25(+) cells obtained from 9 patients before, after 4 weeks. and after 52 weeks of SLIT was assessed in response to the major birch pollen allergen Bet v 1, the homologous apple allergen Mal d 1, or tetanus toxoid. Allergen-induced cytokine responses and FoxP3 expression of T cells were analyzed by using real-time PCR. The role of IL-10 for regulatory activity of T cells was investigated. Results: After 4 weeks, higher frequencies of circulating CD4(+)CD25(+) T cells were detected together with increased FoxP3 and IL-10 and reduced IL-4 and IFN-gamma mRNA expression levels compared with those before SLIT. Proliferation to all 3 antigens was markedly reduced but increased significantly after depletion of CD25(+) cells or addition of anti-IL-10 antibodies. After 52 weeks, proliferation in response to Mal d I or tetanus toxoid returned to pre-SLIT levels, whereas Bet v I-induced proliferation remained significantly suppressed and was enhanced by neither depletion of CD25(+) cells nor addition of anti-IL-10 antibodies. In parallel, increased IFN-gamma and reduced IL-4, IL-10, and FoxP3 mRNA expression was detected. Neither TGF-beta levels nor cell-cell contact-mediated suppression of CD4(+)CD25(+) cells changed during the course of SLIT. Conclusion: SLIT induces regulatory T-cell suppression through IL-10 during the early phase and specific nonreactivity and immune deviation of allergen-specific T cells during the later phase of therapy. Clinical implications: SLIT induces immune mechanisms comparable with subcutaneous specific immunotherapy.. specific immunotherapy| sublingual immunotherapy| t-cell tolerance| immune deviation| regulatory t cells| bet v 1| il-10|birch-pollen allergen| bet v 1| dust mite immunotherapy| grass-pollen| immunological changes| cross-reactivity| oral tolerance| major allergen| ifn-gamma| in-vitro.	SEP-2007	specific immunotherapy| sublingual immunotherapy| t-cell tolerance| immune deviation| regulatory t cells| bet v 1| il-10|birch-pollen allergen| bet v 1| dust mite immunotherapy| grass-pollen| immunological changes| cross-reactivity| oral tolerance| major allergen| ifn-gamma| in-vitro	Bohle, B; Kinaciyan, T; Gerstmayr, M; Radakovics, A; Jahn-Schmid, B; Ebner, C	Sublingual immunotherapy induces IL-10-producing T regulatory cells, allergen-specific T-cell tolerance, and immune deviation		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	specific immunotherapy; sublingual immunotherapy; T-cell tolerance; immune deviation; regulatory T cells; Bet v 1; IL-10	BIRCH-POLLEN ALLERGEN; BET V 1; DUST MITE IMMUNOTHERAPY; GRASS-POLLEN; IMMUNOLOGICAL CHANGES; CROSS-REACTIVITY; ORAL TOLERANCE; MAJOR ALLERGEN; IFN-GAMMA; IN-VITRO	Background: The immunologic mechanisms underlying sublingual immunotherapy (SLIT) are still unclear, particularly the role of regulatory T cells. Objective: We sought to characterize allergen-specific T-cell responses during successful birch pollen SLIT. Methods: Proliferation of PBMCs and PBMCs depleted of CD25(+) cells obtained from 9 patients before, after 4 weeks. and after 52 weeks of SLIT was assessed in response to the major birch pollen allergen Bet v 1, the homologous apple allergen Mal d 1, or tetanus toxoid. Allergen-induced cytokine responses and FoxP3 expression of T cells were analyzed by using real-time PCR. The role of IL-10 for regulatory activity of T cells was investigated. Results: After 4 weeks, higher frequencies of circulating CD4(+)CD25(+) T cells were detected together with increased FoxP3 and IL-10 and reduced IL-4 and IFN-gamma mRNA expression levels compared with those before SLIT. Proliferation to all 3 antigens was markedly reduced but increased significantly after depletion of CD25(+) cells or addition of anti-IL-10 antibodies. After 52 weeks, proliferation in response to Mal d I or tetanus toxoid returned to pre-SLIT levels, whereas Bet v I-induced proliferation remained significantly suppressed and was enhanced by neither depletion of CD25(+) cells nor addition of anti-IL-10 antibodies. In parallel, increased IFN-gamma and reduced IL-4, IL-10, and FoxP3 mRNA expression was detected. Neither TGF-beta levels nor cell-cell contact-mediated suppression of CD4(+)CD25(+) cells changed during the course of SLIT. Conclusion: SLIT induces regulatory T-cell suppression through IL-10 during the early phase and specific nonreactivity and immune deviation of allergen-specific T cells during the later phase of therapy. Clinical implications: SLIT induces immune mechanisms comparable with subcutaneous specific immunotherapy.	46	234	2007	7	10.1016/j.jaci.2007.06.013	Allergy; Immunology
Pulmonary perspective - Obesity and asthma. Asthma and obesity are prevalent disorders, each with a significant public health impact, and a large and growing body of literature suggests an association between the two. The systemic inflammatory milieu in obesity leads to metabolic and cardiovascular complications, but whether this environment alters asthma risk or phenotype is not yet known. Animal experiments have evaluated the effects of leptin and obesity on airway inflammation in response to both allergic and nonallergic exposures and suggest that airway inflammatory response is enhanced by both endogenous and exogenous leptin. Cross-sectional and prospective cohort studies of humans have shown a modest overall increase in asthma incidence and prevalence in the obese, although body mass index does not appear be a significant modifier of asthma severity. Studying the obesity-asthma relationship in large cohorts, in which self-reports are frequently used to ascertain the diagnosis of asthma, has been complicated by alterations in pulmonary physiology caused by obesity, which may lead to dyspnea or other respiratory symptoms but do not fulfill accepted physiologic criteria for asthma. Recent investigations toward elucidating a shared genetic basis for these two disorders have identified polymorphisms in specific regions of chromosomes 5q, 6p, 11q13, and 12q, each of which contains one or more genes encoding receptors relevant to asthma, inflammation, and metabolic disorders, including the beta(2)-adrenergic receptor gene ADRB2 and the glucocorticoid receptor gene NR3C1. Further research is warranted to synthesize these disparate observations into a cohesive understanding of the relationship between obesity and asthma.. asthma| epidemiology| inflammation| obesity| pathogenesis|body-mass index| adult-onset asthma| adipose-tissue| morbid-obesity| weight-loss| airway hyperresponsiveness| gastroesophageal-reflux| respiratory-function| prospective cohort| childhood asthma.	JUL 15-2006	asthma| epidemiology| inflammation| obesity| pathogenesis|body-mass index| adult-onset asthma| adipose-tissue| morbid-obesity| weight-loss| airway hyperresponsiveness| gastroesophageal-reflux| respiratory-function| prospective cohort| childhood asthma	Beuther, DA; Weiss, ST; Sutherland, ER	Pulmonary perspective - Obesity and asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; epidemiology; inflammation; obesity; pathogenesis	BODY-MASS INDEX; ADULT-ONSET ASTHMA; ADIPOSE-TISSUE; MORBID-OBESITY; WEIGHT-LOSS; AIRWAY HYPERRESPONSIVENESS; GASTROESOPHAGEAL-REFLUX; RESPIRATORY-FUNCTION; PROSPECTIVE COHORT; CHILDHOOD ASTHMA	Asthma and obesity are prevalent disorders, each with a significant public health impact, and a large and growing body of literature suggests an association between the two. The systemic inflammatory milieu in obesity leads to metabolic and cardiovascular complications, but whether this environment alters asthma risk or phenotype is not yet known. Animal experiments have evaluated the effects of leptin and obesity on airway inflammation in response to both allergic and nonallergic exposures and suggest that airway inflammatory response is enhanced by both endogenous and exogenous leptin. Cross-sectional and prospective cohort studies of humans have shown a modest overall increase in asthma incidence and prevalence in the obese, although body mass index does not appear be a significant modifier of asthma severity. Studying the obesity-asthma relationship in large cohorts, in which self-reports are frequently used to ascertain the diagnosis of asthma, has been complicated by alterations in pulmonary physiology caused by obesity, which may lead to dyspnea or other respiratory symptoms but do not fulfill accepted physiologic criteria for asthma. Recent investigations toward elucidating a shared genetic basis for these two disorders have identified polymorphisms in specific regions of chromosomes 5q, 6p, 11q13, and 12q, each of which contains one or more genes encoding receptors relevant to asthma, inflammation, and metabolic disorders, including the beta(2)-adrenergic receptor gene ADRB2 and the glucocorticoid receptor gene NR3C1. Further research is warranted to synthesize these disparate observations into a cohesive understanding of the relationship between obesity and asthma.	81	234	2006	8	10.1164/rccm.200602-231PP	General & Internal Medicine; Respiratory System
Inner City Asthma Study: Relationships among sensitivity, allergen exposure, and asthma morbidity. Background: Asthma-associated morbidity is rising, especially in inner city children. Objective: We evaluated the allergen sensitivities, allergen exposures, and associated morbidity for participants in the Inner City Asthma Study. We also determined geographic variations of indoor allergen levels. Methods: Nine hundred thirty-seven inner city children 5 to 11 years old with moderate to severe asthma underwent allergen skin testing. Bedroom dust samples were evaluated for Der p 1, Der f 1, Bla g 1, Fel d 1, and Can f 1. Results: Skin test sensitivities to cockroach (69%), dust mites (62%), and molds (50%) predominated, with marked study site-specific differences. Cockroach sensitivity was highest in the Bronx, New York, and Dallas (81.2%, 78.7%, and 78.5%, respectively), and dust mite sensitivity was highest in Dallas and Seattle (83.7% and 78.0%, respectively). A majority of homes in Chicago, New York, and the Bronx had cockroach allergen levels greater than 2 U/g, and a majority of those in Dallas and Seattle had dust mite allergen levels greater than 2 mu g/g. Levels of both of these allergens were influenced by housing type. Cockroach allergen levels were highest in high-rise apartments, whereas dust mite allergen levels were highest in detached homes. Children who were both sensitive and exposed to cockroach allergen had significantly more asthma symptom days, more caretaker interrupted sleep, and more school days missed than children who were not sensitive or exposed. Conclusion: Geographic differences in allergen exposure and sensitivity exist among inner city children. Cockroach exposure and sensitivity predominate in the Northeast, whereas dust mite exposure and sensitivity are highest in the South and Northwest. Cockroach allergen appears to have a greater effect on asthma morbidity than dust mite or pet allergen in these children.. asthma| allergen exposure| allergen sensitivity| morbidity| allergens| cockroach| dust mite| cat| dog|risk-factors| childhood asthma| indoor allergens| cockroach allergen| management program| cat allergen| children| sensitization| severity| mite.	MAR-2005	asthma| allergen exposure| allergen sensitivity| morbidity| allergens| cockroach| dust mite| cat| dog|risk-factors| childhood asthma| indoor allergens| cockroach allergen| management program| cat allergen| children| sensitization| severity| mite	Gruchalla, RS; Pongracic, J; Plaut, M; Evans, R; Visness, CM; Walter, M; Crain, EF; Kattan, M; Morgan, WJ; Steinbach, S; Stout, J; Malindzak, G; Smartt, E; Mitchell, H	Inner City Asthma Study: Relationships among sensitivity, allergen exposure, and asthma morbidity		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; allergen exposure; allergen sensitivity; morbidity; allergens; cockroach; dust mite; cat; dog	RISK-FACTORS; CHILDHOOD ASTHMA; INDOOR ALLERGENS; COCKROACH ALLERGEN; MANAGEMENT PROGRAM; CAT ALLERGEN; CHILDREN; SENSITIZATION; SEVERITY; MITE	Background: Asthma-associated morbidity is rising, especially in inner city children. Objective: We evaluated the allergen sensitivities, allergen exposures, and associated morbidity for participants in the Inner City Asthma Study. We also determined geographic variations of indoor allergen levels. Methods: Nine hundred thirty-seven inner city children 5 to 11 years old with moderate to severe asthma underwent allergen skin testing. Bedroom dust samples were evaluated for Der p 1, Der f 1, Bla g 1, Fel d 1, and Can f 1. Results: Skin test sensitivities to cockroach (69%), dust mites (62%), and molds (50%) predominated, with marked study site-specific differences. Cockroach sensitivity was highest in the Bronx, New York, and Dallas (81.2%, 78.7%, and 78.5%, respectively), and dust mite sensitivity was highest in Dallas and Seattle (83.7% and 78.0%, respectively). A majority of homes in Chicago, New York, and the Bronx had cockroach allergen levels greater than 2 U/g, and a majority of those in Dallas and Seattle had dust mite allergen levels greater than 2 mu g/g. Levels of both of these allergens were influenced by housing type. Cockroach allergen levels were highest in high-rise apartments, whereas dust mite allergen levels were highest in detached homes. Children who were both sensitive and exposed to cockroach allergen had significantly more asthma symptom days, more caretaker interrupted sleep, and more school days missed than children who were not sensitive or exposed. Conclusion: Geographic differences in allergen exposure and sensitivity exist among inner city children. Cockroach exposure and sensitivity predominate in the Northeast, whereas dust mite exposure and sensitivity are highest in the South and Northwest. Cockroach allergen appears to have a greater effect on asthma morbidity than dust mite or pet allergen in these children.	22	233	2005	8	10.1016/j.jaci.2004.12.006	Allergy; Immunology
Cough and bronchial responsiveness in firefighters at the World Trade Center site. Background: Workers from the Fire Department of New York City were exposed to a variety of inhaled materials during and after the collapse of the World Trade Center. We evaluated clinical features in a series of 332 firefighters in whom severe cough developed after exposure and the prevalence and severity of bronchial hyperreactivity in firefighters without severe cough classified according to the level of exposure. Methods: ``World Trade Center cough'' was defined as a persistent cough that developed after exposure to the site and was accompanied by respiratory symptoms severe enough to require medical leave for at least four weeks. Evaluation of exposed firefighters included completion of a standard questionnaire, spirometry, airway-responsiveness testing, and chest imaging. Results: In the first six months after September 11, 2001, World Trade Center cough occurred in 128 of 1636 firefighters with a high level of exposure (8 percent), 187 of 6958 with a moderate level of exposure (3 percent), and 17 of 1320 with a low level of exposure (1 percent). In addition, 95 percent had symptoms of dyspnea, 87 percent had gastroesophageal reflux disease, and 54 percent had nasal congestion. Of those tested before treatment of World Trade Center cough, 63 percent of firefighters (149 of 237) had a response to a bronchodilator and 24 percent (9 of 37) had bronchial hyperreactivity. Chest radiographs were unchanged from precollapse findings in 319 of the 332 with World Trade Center cough. Among the cohort without severe cough, bronchial hyperreactivity was present in 77 firefighters with a high level of exposure (23 percent) and 26 with a moderate level of exposure (8 percent). Conclusions: Intense, short-term exposure to materials generated during the collapse of the World Trade Center was associated with bronchial responsiveness and the development of cough. Clinical and physiological severity was related to the intensity of exposure.. high-resolution ct| airway responsiveness| respiratory symptoms| occupational asthma| persistent asthma| population-sample| methacholine| exposure| isocyanates| inhalation.	SEP 12-2002	high-resolution ct| airway responsiveness| respiratory symptoms| occupational asthma| persistent asthma| population-sample| methacholine| exposure| isocyanates| inhalation	Prezant, DJ; Weiden, M; Banauch, GI; McGuinness, G; Rom, WN; Aldrich, TK; Kelly, KJ	Cough and bronchial responsiveness in firefighters at the World Trade Center site		NEW ENGLAND JOURNAL OF MEDICINE		HIGH-RESOLUTION CT; AIRWAY RESPONSIVENESS; RESPIRATORY SYMPTOMS; OCCUPATIONAL ASTHMA; PERSISTENT ASTHMA; POPULATION-SAMPLE; METHACHOLINE; EXPOSURE; ISOCYANATES; INHALATION	Background: Workers from the Fire Department of New York City were exposed to a variety of inhaled materials during and after the collapse of the World Trade Center. We evaluated clinical features in a series of 332 firefighters in whom severe cough developed after exposure and the prevalence and severity of bronchial hyperreactivity in firefighters without severe cough classified according to the level of exposure. Methods: ``World Trade Center cough'' was defined as a persistent cough that developed after exposure to the site and was accompanied by respiratory symptoms severe enough to require medical leave for at least four weeks. Evaluation of exposed firefighters included completion of a standard questionnaire, spirometry, airway-responsiveness testing, and chest imaging. Results: In the first six months after September 11, 2001, World Trade Center cough occurred in 128 of 1636 firefighters with a high level of exposure (8 percent), 187 of 6958 with a moderate level of exposure (3 percent), and 17 of 1320 with a low level of exposure (1 percent). In addition, 95 percent had symptoms of dyspnea, 87 percent had gastroesophageal reflux disease, and 54 percent had nasal congestion. Of those tested before treatment of World Trade Center cough, 63 percent of firefighters (149 of 237) had a response to a bronchodilator and 24 percent (9 of 37) had bronchial hyperreactivity. Chest radiographs were unchanged from precollapse findings in 319 of the 332 with World Trade Center cough. Among the cohort without severe cough, bronchial hyperreactivity was present in 77 firefighters with a high level of exposure (23 percent) and 26 with a moderate level of exposure (8 percent). Conclusions: Intense, short-term exposure to materials generated during the collapse of the World Trade Center was associated with bronchial responsiveness and the development of cough. Clinical and physiological severity was related to the intensity of exposure.	37	233	2002	10	10.1056/NEJMoa021300	General & Internal Medicine
New perspectives on epidermal barrier dysfunction in atopic dermatitis: Gene-environment interactions. Atopic dermatitis (AD) is a multifactorial, chronic inflammatory skin disorder in which genetic mutations and cutaneous hyperreactivity to environmental stimuli play a causative role. Genetic mutations alone might not be enough to cause clinical manifestations of AD, and this review will propose a new perspective on the importance of epidermal barrier dysfunction in genetically predisposed individuals, predisposing them to the harmful effects of environmental agents. The skin barrier is known to be damaged in patients with AD, both in acute eczematous lesions and also in clinically unaffected skin. Skin barrier function can be impaired first by a genetic predisposition to produce increased levels of stratum corneum chymotryptic enzyme. This protease enzyme causes premature breakdown of corneodesmosomes, leading to impairment of the epidermal barrier. The addition of environmental interactions, such as washing with soap and detergents, or long-term application of topical corticosteroids can further increase production of stratum corneum chymotryptic enzyme and impair epidermal barrier function. The epidermal barrier can also be damaged by exogenous proteases from house dust mites and Staphylococcus aureus. One or more of these factors in combination might lead to a defective barrier, thereby increasing the risk of allergen penetration and succeeding inflammatory reaction, thus contributing to exacerbations of this disease.. atopic dermatitis| eczema| environmental triggers| genome| proteases| protease inhibitors| skin barrier dysfunction| topical corticosteroids|corneum chymotryptic enzyme| mast-cell chymase| skin in-vivo| cutaneous permeability barrier| corticosteroid-induced atrophy| clinically uninvolved skin| thin-layer chromatography| human stratum-corneum| dust-mite allergen| netherton-syndrome.	JUL-2006	atopic dermatitis| eczema| environmental triggers| genome| proteases| protease inhibitors| skin barrier dysfunction| topical corticosteroids|corneum chymotryptic enzyme| mast-cell chymase| skin in-vivo| cutaneous permeability barrier| corticosteroid-induced atrophy| clinically uninvolved skin| thin-layer chromatography| human stratum-corneum| dust-mite allergen| netherton-syndrome	Cork, MJ; Robinson, DA; Vasilopoulos, Y; Ferguson, A; Moustafa, M; MacGowan, A; Duff, GW; Ward, SJ; Tazi-Ahnini, R	New perspectives on epidermal barrier dysfunction in atopic dermatitis: Gene-environment interactions		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopic dermatitis; eczema; environmental triggers; genome; proteases; protease inhibitors; skin barrier dysfunction; topical corticosteroids	CORNEUM CHYMOTRYPTIC ENZYME; MAST-CELL CHYMASE; SKIN IN-VIVO; CUTANEOUS PERMEABILITY BARRIER; CORTICOSTEROID-INDUCED ATROPHY; CLINICALLY UNINVOLVED SKIN; THIN-LAYER CHROMATOGRAPHY; HUMAN STRATUM-CORNEUM; DUST-MITE ALLERGEN; NETHERTON-SYNDROME	Atopic dermatitis (AD) is a multifactorial, chronic inflammatory skin disorder in which genetic mutations and cutaneous hyperreactivity to environmental stimuli play a causative role. Genetic mutations alone might not be enough to cause clinical manifestations of AD, and this review will propose a new perspective on the importance of epidermal barrier dysfunction in genetically predisposed individuals, predisposing them to the harmful effects of environmental agents. The skin barrier is known to be damaged in patients with AD, both in acute eczematous lesions and also in clinically unaffected skin. Skin barrier function can be impaired first by a genetic predisposition to produce increased levels of stratum corneum chymotryptic enzyme. This protease enzyme causes premature breakdown of corneodesmosomes, leading to impairment of the epidermal barrier. The addition of environmental interactions, such as washing with soap and detergents, or long-term application of topical corticosteroids can further increase production of stratum corneum chymotryptic enzyme and impair epidermal barrier function. The epidermal barrier can also be damaged by exogenous proteases from house dust mites and Staphylococcus aureus. One or more of these factors in combination might lead to a defective barrier, thereby increasing the risk of allergen penetration and succeeding inflammatory reaction, thus contributing to exacerbations of this disease.	215	232	2006	19	10.1016/j.jaci.2006.04.042	Allergy; Immunology
Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children. Prenatal exposure to polychlorinated biphenyls (PCBs) and dioxins is associated with changes in the T-cell lymphocyte population in healthy Dutch infants. We investigated whether these changes persist into later childhood and whether background exposure to PCBs and dioxins is associated with the prevalence of infectious or allergic diseases and humoral immunity at preschool age. The total study group consisted of 207 healthy mother-infant pairs. We estimated prenatal exposure to PCBs and dioxins by the sum of PCBs 118, 138, 153, and 180 (Sigma PCB) in maternal and cord plasma and in breast-fed infants by the dioxin, planar, and mono-ortho PCB toxic equivalent (TEQ) levels in human milk At 42 months of age, current body burden was estimated by the Sigma PCB in plasma. We assessed the prevalence of infectious and allergic diseases by parent questionnaire, and measured humoral immunity by antibody levels for mumps, measles, and rubella after primary vaccination. We performed immunologic marker analyses of lymphocytes in a subgroup of 85 children. Prenatal PCB exposure was associated with an increased number of lymphocytes, T-cells, and CD3CD8(+) (cytotoxic), CD4(+)CD45RO(+) (memory), T-cell receptor (TcR) alpha beta (+), and CD3(+)HLA-DR+ (activated) T cells and lower antibody levels to mumps and measles at preschool age. Adjusted for confounders, prenatal PCB exposure was associated with less shortness of breath with wheeze, and current PCB body burden was associated with a higher prevalence of recurrent middle-ear infections and of chicken pox and a lower prevalence of allergic reactions. A higher dioxin TEQ was associated with a higher prevalence of coughing, chest congestion, and phlegm. We conclude that in Dutch preschool children the effects of perinatal background exposure to PCBs and dioxins persist into childhood and might be associated with a greater susceptibility to infectious diseases. Common infections acquired early in life may prevent the development of allergy, so PCB exposure might be associated with a lower prevalence of allergic diseases.. allergic diseases| antibody levels| breast-feeding| infectious diseases| leucocyte (sub)populations| pcbs| pcdds| pcdfs|lymphocyte subsets| otitis-media| infants| antibodies| dibenzofurans| netherlands| prevalence| childhood| measles| asthma.	DEC-2000	allergic diseases| antibody levels| breast-feeding| infectious diseases| leucocyte (sub)populations| pcbs| pcdds| pcdfs|lymphocyte subsets| otitis-media| infants| antibodies| dibenzofurans| netherlands| prevalence| childhood| measles| asthma	Weisglas-Kuperus, N; Patandin, S; Berbers, GAM; Sas, TCJ; Mulder, PGH; Sauer, PJJ; Hooijkaas, H	Immunologic effects of background exposure to polychlorinated biphenyls and dioxins in Dutch preschool children		ENVIRONMENTAL HEALTH PERSPECTIVES	allergic diseases; antibody levels; breast-feeding; infectious diseases; leucocyte (sub)populations; PCBs; PCDDs; PCDFs	LYMPHOCYTE SUBSETS; OTITIS-MEDIA; INFANTS; ANTIBODIES; DIBENZOFURANS; NETHERLANDS; PREVALENCE; CHILDHOOD; MEASLES; ASTHMA	Prenatal exposure to polychlorinated biphenyls (PCBs) and dioxins is associated with changes in the T-cell lymphocyte population in healthy Dutch infants. We investigated whether these changes persist into later childhood and whether background exposure to PCBs and dioxins is associated with the prevalence of infectious or allergic diseases and humoral immunity at preschool age. The total study group consisted of 207 healthy mother-infant pairs. We estimated prenatal exposure to PCBs and dioxins by the sum of PCBs 118, 138, 153, and 180 (Sigma PCB) in maternal and cord plasma and in breast-fed infants by the dioxin, planar, and mono-ortho PCB toxic equivalent (TEQ) levels in human milk At 42 months of age, current body burden was estimated by the Sigma PCB in plasma. We assessed the prevalence of infectious and allergic diseases by parent questionnaire, and measured humoral immunity by antibody levels for mumps, measles, and rubella after primary vaccination. We performed immunologic marker analyses of lymphocytes in a subgroup of 85 children. Prenatal PCB exposure was associated with an increased number of lymphocytes, T-cells, and CD3CD8(+) (cytotoxic), CD4(+)CD45RO(+) (memory), T-cell receptor (TcR) alpha beta (+), and CD3(+)HLA-DR+ (activated) T cells and lower antibody levels to mumps and measles at preschool age. Adjusted for confounders, prenatal PCB exposure was associated with less shortness of breath with wheeze, and current PCB body burden was associated with a higher prevalence of recurrent middle-ear infections and of chicken pox and a lower prevalence of allergic reactions. A higher dioxin TEQ was associated with a higher prevalence of coughing, chest congestion, and phlegm. We conclude that in Dutch preschool children the effects of perinatal background exposure to PCBs and dioxins persist into childhood and might be associated with a greater susceptibility to infectious diseases. Common infections acquired early in life may prevent the development of allergy, so PCB exposure might be associated with a lower prevalence of allergic diseases.	30	232	2000	5	10.2307/3434834	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years. Background: Fractional exhaled nitric oxide (FENO) is used in monitoring of asthma. Objectives: The aim of this multicenter study was to establish normal values of FENO and assess feasibility in children with a standardized method and equipment approved for clinical use. Methods: FENO was measured in healthy subjects of 4 to 17 years according to American Thoracic Society guidelines (single breath online, exhalation flow 50 mL/s) with a chemilumineseence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden) in 3 European and 2 US centers. Each child performed 3 acceptable nitric oxide measurements within 6 attempts and completed an extended International Study of Asthma and Allergy in Children questionnaire. Results: Measurement of FENO was attempted in 522 children. Four hundred five children completed the study according to the protocol. Geometric mean FENO in 405 children was 9.7 pph, and the upper 95% confidence limit was 25.2 pph. FENO increased significantly with age, and higher FENO was seen in children with self-reported rhinitis/conjunctivitis or hay fever. The success rate was age-dependent and improved from 40% in the children 4 years old to almost 100%, front the age of 10 years. The repeatability of 3 approved measurements was 1.6 ppb (95% CI, 1.49-1.64 ppb). Conclusion: FENO in healthy children is below 15 to 25 pph depending on age and self-reported atopy. Measurement of FENO by NIOX is simple and safe and has a good repeatability. Feasibility depends on age and may be difficult in the preschool child.. exhaled nitric oxide| children| normal values|exercise-induced bronchoconstriction| asthmatic-children| air| decreases| sensitization| rhinitis| online| values| adults| atopy.	JUN-2005	exhaled nitric oxide| children| normal values|exercise-induced bronchoconstriction| asthmatic-children| air| decreases| sensitization| rhinitis| online| values| adults| atopy	Buchvald, F; Baraidi, E; Carraro, S; Gaston, B; De Jongste, J; Pijnenburg, MWH; Silkoff, PE; Bisgaard, H	Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	exhaled nitric oxide; children; normal values	EXERCISE-INDUCED BRONCHOCONSTRICTION; ASTHMATIC-CHILDREN; AIR; DECREASES; SENSITIZATION; RHINITIS; ONLINE; VALUES; ADULTS; ATOPY	Background: Fractional exhaled nitric oxide (FENO) is used in monitoring of asthma. Objectives: The aim of this multicenter study was to establish normal values of FENO and assess feasibility in children with a standardized method and equipment approved for clinical use. Methods: FENO was measured in healthy subjects of 4 to 17 years according to American Thoracic Society guidelines (single breath online, exhalation flow 50 mL/s) with a chemilumineseence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden) in 3 European and 2 US centers. Each child performed 3 acceptable nitric oxide measurements within 6 attempts and completed an extended International Study of Asthma and Allergy in Children questionnaire. Results: Measurement of FENO was attempted in 522 children. Four hundred five children completed the study according to the protocol. Geometric mean FENO in 405 children was 9.7 pph, and the upper 95% confidence limit was 25.2 pph. FENO increased significantly with age, and higher FENO was seen in children with self-reported rhinitis/conjunctivitis or hay fever. The success rate was age-dependent and improved from 40% in the children 4 years old to almost 100%, front the age of 10 years. The repeatability of 3 approved measurements was 1.6 ppb (95% CI, 1.49-1.64 ppb). Conclusion: FENO in healthy children is below 15 to 25 pph depending on age and self-reported atopy. Measurement of FENO by NIOX is simple and safe and has a good repeatability. Feasibility depends on age and may be difficult in the preschool child.	36	231	2005	7	10.1016/j.jaci.2005.03.020	Allergy; Immunology
Household food insufficiency is associated with poorer health. The purposes of this study were to estimate the prevalence of household food insufficiency in Canada, to identify sociodemographic characteristics of households most likely to report food insufficiency and to examine the relationship between food insufficiency and physical, mental and social health. These objectives were achieved through an analysis of data from the 1996/1997 National Population Health Survey. An estimated 4% of Canadians, 1.1 million people, were found to be living in food-insufficient households. Single-parent families, households reporting their major source of income as welfare, unemployment insurance or workers' compensation, those who did not own their own homes and households in Western Canada were more likely to report food insufficiency. The likelihood of reporting food insufficiency increased dramatically as income adequacy deteriorated. Individuals from food-insufficient households had significantly higher odds of reporting poor/fair health, of having poor functional health, restricted activity and multiple chronic conditions, of suffering from major depression and distress, and of having poor social support. Individuals in food-insufficient households were also more likely to report heart disease, diabetes, high blood pressure and food allergies. Men in food-insufficient households were less likely to be overweight; after adjusting for potentially confounding variables, no other associations were found between food insufficiency and body mass index. These findings suggest that food insufficiency is one dimension of a more pervasive vulnerability to a range of physical, mental and social health problems among households struggling with economic constraints.. food insecurity| health status| welfare| body mass index| canada|body-mass index| nutrition examination survey| childrens feeding programs| 3rd national-health| population health| united-states| atlantic canada| family income| insecurity| hunger.	JAN-2003	food insecurity| health status| welfare| body mass index| canada|body-mass index| nutrition examination survey| childrens feeding programs| 3rd national-health| population health| united-states| atlantic canada| family income| insecurity| hunger	Vozoris, NT; Tarasuk, VS	Household food insufficiency is associated with poorer health		JOURNAL OF NUTRITION	food insecurity; health status; welfare; body mass index; Canada	BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; CHILDRENS FEEDING PROGRAMS; 3RD NATIONAL-HEALTH; POPULATION HEALTH; UNITED-STATES; ATLANTIC CANADA; FAMILY INCOME; INSECURITY; HUNGER	The purposes of this study were to estimate the prevalence of household food insufficiency in Canada, to identify sociodemographic characteristics of households most likely to report food insufficiency and to examine the relationship between food insufficiency and physical, mental and social health. These objectives were achieved through an analysis of data from the 1996/1997 National Population Health Survey. An estimated 4% of Canadians, 1.1 million people, were found to be living in food-insufficient households. Single-parent families, households reporting their major source of income as welfare, unemployment insurance or workers' compensation, those who did not own their own homes and households in Western Canada were more likely to report food insufficiency. The likelihood of reporting food insufficiency increased dramatically as income adequacy deteriorated. Individuals from food-insufficient households had significantly higher odds of reporting poor/fair health, of having poor functional health, restricted activity and multiple chronic conditions, of suffering from major depression and distress, and of having poor social support. Individuals in food-insufficient households were also more likely to report heart disease, diabetes, high blood pressure and food allergies. Men in food-insufficient households were less likely to be overweight; after adjusting for potentially confounding variables, no other associations were found between food insufficiency and body mass index. These findings suggest that food insufficiency is one dimension of a more pervasive vulnerability to a range of physical, mental and social health problems among households struggling with economic constraints.	70	231	2003	7		Nutrition & Dietetics
Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma. Asthma is a common respiratory disease that is characterized by variable airways obstruction caused by acute and chronic bronchial inflammation; associated phenotypes include bronchial hyperresponsiveness (BHR), elevated total serum immunoglobulin E (IgE) levels, and skin tests positive to common allergens. Binding of interleukin-13 (IL13) or interleukin-4 (IL4) to the IL4 receptor (IL4R) induces the initial response for Th2 lymphocyte polarization. Both IL13 and IL4 are produced by Th2 cells and are capable of inducing isotype class-switching of B-cells to produce IgE after allergen exposure. These cytokines also share a common receptor component, IL4R. We have investigated five IL4RA single-nucleotide polymorphisms in a population of Dutch families ascertained through a proband with asthma. By considering the probands and their spouses as an unrelated sample, we observed significant associations of atopy and asthma-related phenotypes with several IL4RA polymorphisms, including S478P and total serum IgE levels (P=.0007). A significant gene-gene interaction between S478P in IL4RA and the - 1111 promoter variation in IL13, previously shown to be associated with BHR (P = .003), was detected. Individuals with the risk genotype for both genes were at almost five times greater risk for the development of asthma compared to individuals with both nonrisk genotypes (P = .0004). These data suggest that variations in IL4RA contribute to elevated total serum IgE levels, and interaction between IL4RA and IL13 markedly increases an individual's susceptibility to asthma.. skin-test reactivity| serum ige levels| interleukin-4 receptor| airway inflammation| bronchial responsiveness| il4-receptor gene| atopic asthma| alpha-gene| association| il-4.	JAN-2002	skin-test reactivity| serum ige levels| interleukin-4 receptor| airway inflammation| bronchial responsiveness| il4-receptor gene| atopic asthma| alpha-gene| association| il-4	Howard, TD; Koppelman, GH; Xu, JF; Zheng, SQL; Postma, DS; Meyers, DA; Bleecker, ER	Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma		AMERICAN JOURNAL OF HUMAN GENETICS		SKIN-TEST REACTIVITY; SERUM IGE LEVELS; INTERLEUKIN-4 RECEPTOR; AIRWAY INFLAMMATION; BRONCHIAL RESPONSIVENESS; IL4-RECEPTOR GENE; ATOPIC ASTHMA; ALPHA-GENE; ASSOCIATION; IL-4	Asthma is a common respiratory disease that is characterized by variable airways obstruction caused by acute and chronic bronchial inflammation; associated phenotypes include bronchial hyperresponsiveness (BHR), elevated total serum immunoglobulin E (IgE) levels, and skin tests positive to common allergens. Binding of interleukin-13 (IL13) or interleukin-4 (IL4) to the IL4 receptor (IL4R) induces the initial response for Th2 lymphocyte polarization. Both IL13 and IL4 are produced by Th2 cells and are capable of inducing isotype class-switching of B-cells to produce IgE after allergen exposure. These cytokines also share a common receptor component, IL4R. We have investigated five IL4RA single-nucleotide polymorphisms in a population of Dutch families ascertained through a proband with asthma. By considering the probands and their spouses as an unrelated sample, we observed significant associations of atopy and asthma-related phenotypes with several IL4RA polymorphisms, including S478P and total serum IgE levels (P=.0007). A significant gene-gene interaction between S478P in IL4RA and the - 1111 promoter variation in IL13, previously shown to be associated with BHR (P = .003), was detected. Individuals with the risk genotype for both genes were at almost five times greater risk for the development of asthma compared to individuals with both nonrisk genotypes (P = .0004). These data suggest that variations in IL4RA contribute to elevated total serum IgE levels, and interaction between IL4RA and IL13 markedly increases an individual's susceptibility to asthma.	29	231	2002	7	10.1086/338242	Genetics & Heredity
Atopic diseases, allergic sensitization, and exposure to traffic-related air pollution in children. Rationale: In vitro studies, animal experiments, and human exposure studies have shown how ambient air pollution increases the risk of atopic diseases. However, results derived from observational studies are inconsistent. Objectives: To assess the relationship between individual-based exposure to traffic-related air pollutants and allergic disease outcomes in a prospective birth cohort study during the first 6 years of life. Methods: We studied 2,860 children at the age of 4years and 3,061 at the age of 6 years to investigate atopic diseases and allergic sensitization. Long-term exposure to particulate matter (PM2.5), PM2.5 absorbance, and long-term exposure to nitrogen dioxide (NO2) was assessed at residential addresses using geographic information systems based regression models and air pollution measurements. The distance to the nearest main road was used as a surrogate for traffic-related air pollutants. Measurements and Main Results: Strong positive associations were found between the distance to the nearest main road and asthmatic bronchitis, hay fever, eczema, and sensitization. A distance-dependent relationship could be identified, with the highest odds ratios (ORs) for children living less than 50 m from busy streets. For PM2.5 absorbance, statistically significant effects were found for asthmatic bronchitis (OR, 1.56; 95% confidence interval [CI], 1.03-2.37), hay fever (OR, 1.59; 95% CI, 1.11-2.27), and allergic sensitization to pollen (OR, 1.40; 95% CI, 1.20-1.64). NO2 exposure was associated with eczema, whereas no association was found for allergic sensitization. Conclusions: This study provides strong evidence for increased risk of atopic diseases and allergic sensitization when children are exposed to ambient particulate matter.. air pollution| gis| allergic sensitization| allergy|individual estimated exposure| prospective birth cohort| solid food introduction| respiratory health| spatial variability| particulate matter| nitrogen-dioxide| term exposure| symptoms| asthma.	JUN 15-2008	air pollution| gis| allergic sensitization| allergy|individual estimated exposure| prospective birth cohort| solid food introduction| respiratory health| spatial variability| particulate matter| nitrogen-dioxide| term exposure| symptoms| asthma	Morgenstern, V; Zutavern, A; Cyrys, J; Brockow, I; Koletzko, S; Kramer, U; Behrendt, H; Herbarth, O; von Berg, A; Bauer, CP; Wichmann, HE; Heinrich, J	Atopic diseases, allergic sensitization, and exposure to traffic-related air pollution in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	air pollution; GIS; allergic sensitization; allergy	INDIVIDUAL ESTIMATED EXPOSURE; PROSPECTIVE BIRTH COHORT; SOLID FOOD INTRODUCTION; RESPIRATORY HEALTH; SPATIAL VARIABILITY; PARTICULATE MATTER; NITROGEN-DIOXIDE; TERM EXPOSURE; SYMPTOMS; ASTHMA	Rationale: In vitro studies, animal experiments, and human exposure studies have shown how ambient air pollution increases the risk of atopic diseases. However, results derived from observational studies are inconsistent. Objectives: To assess the relationship between individual-based exposure to traffic-related air pollutants and allergic disease outcomes in a prospective birth cohort study during the first 6 years of life. Methods: We studied 2,860 children at the age of 4years and 3,061 at the age of 6 years to investigate atopic diseases and allergic sensitization. Long-term exposure to particulate matter (PM2.5), PM2.5 absorbance, and long-term exposure to nitrogen dioxide (NO2) was assessed at residential addresses using geographic information systems based regression models and air pollution measurements. The distance to the nearest main road was used as a surrogate for traffic-related air pollutants. Measurements and Main Results: Strong positive associations were found between the distance to the nearest main road and asthmatic bronchitis, hay fever, eczema, and sensitization. A distance-dependent relationship could be identified, with the highest odds ratios (ORs) for children living less than 50 m from busy streets. For PM2.5 absorbance, statistically significant effects were found for asthmatic bronchitis (OR, 1.56; 95% confidence interval [CI], 1.03-2.37), hay fever (OR, 1.59; 95% CI, 1.11-2.27), and allergic sensitization to pollen (OR, 1.40; 95% CI, 1.20-1.64). NO2 exposure was associated with eczema, whereas no association was found for allergic sensitization. Conclusions: This study provides strong evidence for increased risk of atopic diseases and allergic sensitization when children are exposed to ambient particulate matter.	42	230	2008	7	10.1164/rccm.200701-036OC	General & Internal Medicine; Respiratory System
Criteria for development of a database for safety evaluation of fragrance ingredients. Over 2000 different ingredients are used in the manufacture of fragrances. The majority of these ingredients have been used for many decades. Despite this long history of use, all of these ingredients need continued monitoring to ensure that each ingredient meets acceptable safety standards. As with other large databases of existing chemicals, fulfilling this need requires an organized approach to identify the most important potential hazards. One such approach, specifically considering the dermal route of exposure as the most relevant one for fragrance ingredients, has been developed. This approach provides a rational selection of materials for review and gives guidance for determining the test data that would normally be considered necessary for the elevation of safety under intended conditions of use. As a first step, the process takes into account the following criteria: quantity of use, consumer exposure, and chemical structure. These are then used for the orderly selection of materials for review with higher quantity, higher exposure, and the presence of defined structural alerts all contributing to a higher priority for review. These structural alerts along with certain exposure and volume limits are then used to develop guidelines for determining the quality and quantity of data considered necessary to support an adequate safety evaluation of the chosen materials, taking into account existing data on the substance itself as well as on closely related analogs. This approach can be considered an alternative to testing; therefore, it is designed to be conservative but not so much so as to require excessive effort when not justified. (C) 2000 Academic Press.. identifying contact allergens| expert-system rulebase| genotoxicity tests| chemical-structure| carcinogenicity| mutagenicity.	APR-2000	identifying contact allergens| expert-system rulebase| genotoxicity tests| chemical-structure| carcinogenicity| mutagenicity	Ford, RA; Domeyer, B; Easterday, O; Maier, K; Middleton, J	Criteria for development of a database for safety evaluation of fragrance ingredients		REGULATORY TOXICOLOGY AND PHARMACOLOGY		IDENTIFYING CONTACT ALLERGENS; EXPERT-SYSTEM RULEBASE; GENOTOXICITY TESTS; CHEMICAL-STRUCTURE; CARCINOGENICITY; MUTAGENICITY	Over 2000 different ingredients are used in the manufacture of fragrances. The majority of these ingredients have been used for many decades. Despite this long history of use, all of these ingredients need continued monitoring to ensure that each ingredient meets acceptable safety standards. As with other large databases of existing chemicals, fulfilling this need requires an organized approach to identify the most important potential hazards. One such approach, specifically considering the dermal route of exposure as the most relevant one for fragrance ingredients, has been developed. This approach provides a rational selection of materials for review and gives guidance for determining the test data that would normally be considered necessary for the elevation of safety under intended conditions of use. As a first step, the process takes into account the following criteria: quantity of use, consumer exposure, and chemical structure. These are then used for the orderly selection of materials for review with higher quantity, higher exposure, and the presence of defined structural alerts all contributing to a higher priority for review. These structural alerts along with certain exposure and volume limits are then used to develop guidelines for determining the quality and quantity of data considered necessary to support an adequate safety evaluation of the chosen materials, taking into account existing data on the substance itself as well as on closely related analogs. This approach can be considered an alternative to testing; therefore, it is designed to be conservative but not so much so as to require excessive effort when not justified. (C) 2000 Academic Press.	38	230	2000	16	10.1006/rtph.1999.1362	Legal Medicine; Pharmacology & Pharmacy; Toxicology
Hospital admissions resulting from preventable adverse drug reactions. BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of hospital admissions. These events can lead to significant morbidity and mortality and financial costs. ADRs that may be preventable might be considered a form of medication error. OBJECTIVE: To assess the potential preventability of ADRs directly related to a patient's hospital admission. METHODS: A retrospective chart review of 437 ADRs occurring during an 11-month period was conducted at a university hospital. A subset of these events leading to hospital admissions was identified for further review. Those that resulted in admission were further examined to determine probability of causality, severity, and preventability. RESULTS: Over 11 months, 158 ADRs were directly related to hospital admission. The relationship of these admissions to drug exposure was determined to be probable or highly probable in 154 (97.4%) of these cases. From this group, 96 (62.3%) of these events were considered potentially preventable, with 23 (24%) considered severe to life-threatening. Characteristics associated with these ADRs included documentation of a toxic drug concentration or abnormal laboratory value (80%), inadequate monitoring of a patient's drug therapy (67%), inappropriate dose (51%), patient noncompliance (33%), drug-drug interaction (26%), contraindication to therapy (3%), and documented allergy (1%). These ADRs resulted in 595 hospital days, with an average length of stay of 6.1 days. CONCLUSIONS: ADRs leading to hospital admissions are often preventable. Approximately 25% of these events were serious to life-threatening. Most resulted from inadequate monitoring of therapy or inappropriate dosing. Patient noncompliance and drug interactions were also common causes. Multidisciplinary prevention strategies among physicians, pharmacists, other healthcare professionals, and patients focusing on communication and education should be targeted.. adverse drug reaction| hospital admission|induced illness| events.	SEP-2002	adverse drug reaction| hospital admission|induced illness| events	McDonnell, PJ; Jacobs, MR	Hospital admissions resulting from preventable adverse drug reactions		ANNALS OF PHARMACOTHERAPY	adverse drug reaction; hospital admission	INDUCED ILLNESS; EVENTS	BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of hospital admissions. These events can lead to significant morbidity and mortality and financial costs. ADRs that may be preventable might be considered a form of medication error. OBJECTIVE: To assess the potential preventability of ADRs directly related to a patient's hospital admission. METHODS: A retrospective chart review of 437 ADRs occurring during an 11-month period was conducted at a university hospital. A subset of these events leading to hospital admissions was identified for further review. Those that resulted in admission were further examined to determine probability of causality, severity, and preventability. RESULTS: Over 11 months, 158 ADRs were directly related to hospital admission. The relationship of these admissions to drug exposure was determined to be probable or highly probable in 154 (97.4%) of these cases. From this group, 96 (62.3%) of these events were considered potentially preventable, with 23 (24%) considered severe to life-threatening. Characteristics associated with these ADRs included documentation of a toxic drug concentration or abnormal laboratory value (80%), inadequate monitoring of a patient's drug therapy (67%), inappropriate dose (51%), patient noncompliance (33%), drug-drug interaction (26%), contraindication to therapy (3%), and documented allergy (1%). These ADRs resulted in 595 hospital days, with an average length of stay of 6.1 days. CONCLUSIONS: ADRs leading to hospital admissions are often preventable. Approximately 25% of these events were serious to life-threatening. Most resulted from inadequate monitoring of therapy or inappropriate dosing. Patient noncompliance and drug interactions were also common causes. Multidisciplinary prevention strategies among physicians, pharmacists, other healthcare professionals, and patients focusing on communication and education should be targeted.	22	229	2002	6	10.1345/aph.1A333	Pharmacology & Pharmacy
Farm environment in childhood prevents the development of allergies. Background A protective effect of infections in early life might explain the firmly reported finding of an inverse association between atopic disorders and large sibships. Objective To study the effect of childhood farm, rural non-farm and urban environment, as well as family size and other factors on the occurrence of asthma, wheezing and atopic disorders up to young adulthood. Methods Data on lifetime prevalence of physician-diagnosed asthma, allergic rhinitis and/or allergic conjunctivitis, atopic dermatitis, as well as self-reported episodic wheezing from 10 667 Finnish first-year university students aged 18-24 years were collected by a postal questionnaire. Associations of lifetime prevalence of the diseases with living on a farm, in a rural non-farm and urban environment during childhood were estimated by logistic regression analysis. Adjustment was made for potential confounding by gender, parental atopy, parental education, number of older siblings, day care outside the home and passive smoking. Results The childhood farm environment independently reduced the risk for physician-diagnosed allergic rhinitis and/or allergic conjunctivitis (adjusted odds ratio 0.63, 95% CI 0.50-0.79, P < 0.001), and for diagnosed asthma and episodic wheezing analysed together (OR 0.71, 95% CI 0.54-0.93, P < 0.05), but not for atopic dermatitis during lifetime. Urban childhood environment did not show independent increased risk when compared with rural non-farm residence. The inverse association of sibship size with the occurrence of allergic rhinitis and/or allergic conjunctivitis was found among subjects with one (OR 0.86, 95% CI 0.77-0.96, P < 0.01) or at least four older siblings (OR 0.47, 95% CI 0.26-0.84, P < 0.05). Conclusion Childhood farm environment seems to have a protective effect against allergic rhinitis and/or conjunctivitis, and more weakly against asthma and wheezing irrespective of family size. Environmental exposure to immune modulating agents, such as environmental mycobacteria and actinomycetes, favouring manifestation of a nonatopic phenotype could explain the finding.. allergic conjunctivitis| allergic rhinitis| asthma| atopic dermatitis| epidemiology| family size| farm environment| rural| urban|skin-test reactivity| hay-fever| respiratory symptoms| sibship size| east-germany| family-size| asthma| atopy| prevalence| children.	FEB-2000	allergic conjunctivitis| allergic rhinitis| asthma| atopic dermatitis| epidemiology| family size| farm environment| rural| urban|skin-test reactivity| hay-fever| respiratory symptoms| sibship size| east-germany| family-size| asthma| atopy| prevalence| children	Kilpelainen, M; Terho, EO; Helenius, H; Koskenvuo, M	Farm environment in childhood prevents the development of allergies		CLINICAL AND EXPERIMENTAL ALLERGY	allergic conjunctivitis; allergic rhinitis; asthma; atopic dermatitis; epidemiology; family size; farm environment; rural; urban	SKIN-TEST REACTIVITY; HAY-FEVER; RESPIRATORY SYMPTOMS; SIBSHIP SIZE; EAST-GERMANY; FAMILY-SIZE; ASTHMA; ATOPY; PREVALENCE; CHILDREN	Background A protective effect of infections in early life might explain the firmly reported finding of an inverse association between atopic disorders and large sibships. Objective To study the effect of childhood farm, rural non-farm and urban environment, as well as family size and other factors on the occurrence of asthma, wheezing and atopic disorders up to young adulthood. Methods Data on lifetime prevalence of physician-diagnosed asthma, allergic rhinitis and/or allergic conjunctivitis, atopic dermatitis, as well as self-reported episodic wheezing from 10 667 Finnish first-year university students aged 18-24 years were collected by a postal questionnaire. Associations of lifetime prevalence of the diseases with living on a farm, in a rural non-farm and urban environment during childhood were estimated by logistic regression analysis. Adjustment was made for potential confounding by gender, parental atopy, parental education, number of older siblings, day care outside the home and passive smoking. Results The childhood farm environment independently reduced the risk for physician-diagnosed allergic rhinitis and/or allergic conjunctivitis (adjusted odds ratio 0.63, 95% CI 0.50-0.79, P < 0.001), and for diagnosed asthma and episodic wheezing analysed together (OR 0.71, 95% CI 0.54-0.93, P < 0.05), but not for atopic dermatitis during lifetime. Urban childhood environment did not show independent increased risk when compared with rural non-farm residence. The inverse association of sibship size with the occurrence of allergic rhinitis and/or allergic conjunctivitis was found among subjects with one (OR 0.86, 95% CI 0.77-0.96, P < 0.01) or at least four older siblings (OR 0.47, 95% CI 0.26-0.84, P < 0.05). Conclusion Childhood farm environment seems to have a protective effect against allergic rhinitis and/or conjunctivitis, and more weakly against asthma and wheezing irrespective of family size. Environmental exposure to immune modulating agents, such as environmental mycobacteria and actinomycetes, favouring manifestation of a nonatopic phenotype could explain the finding.	41	229	2000	8		Allergy; Immunology
Impact of gender on asthma in childhood and adolescence: a GA(2)LEN review. A number of studies have shown gender differences in the prevalence of wheeze and asthma. The aim of this review was to examine published results on gender differences in childhood and adolescent asthma incidence and prevalence, define current concepts and to identify new research needs. A Medline search was performed with the search words (gender OR sex) AND (child OR childhood OR adolescence) AND (asthma). Articles that reported on abscence or prescence of gender differences in asthma were included and reviewed, and cross-references were checked. Boys are consistently reported to have more prevalent wheeze and asthma than girls. In adolescence, the pattern changes and onset of wheeze is more prevalent in females than males. Asthma, after childhood, is more severe in females than in males, and is underdiagnosed and undertreated in female adolescents. Possible explanations for this switch around puberty in the gender susceptibility to develop asthma include hormonal changes and gender-specific differences in environmental exposures. This aspect needs consideration of the doctors and allergists who diagnose and treat asthmatic individuals. In conclusion, sex hormones are likely to play an important role in the development and outcome of the allergic immune response and asthma in particular. By obtaining functional data from appropriate models, the exact underlying mechanisms can be unravelled. To examine the effect of gender-specific differences in environmental exposures and changes of asthma prevalence and severity in puberty, larger populations may need to be investigated.. adolescence| asthma| child| ga(2)len| gender|body-mass index| respiratory symptoms| sex-differences| lung-function| birth cohort| bronchial responsiveness| emergency-department| diagnosed asthma| swiss children| risk-factors.	JAN-2008	adolescence| asthma| child| ga(2)len| gender|body-mass index| respiratory symptoms| sex-differences| lung-function| birth cohort| bronchial responsiveness| emergency-department| diagnosed asthma| swiss children| risk-factors	Almqvist, C; Worm, M; Leynaert, B	Impact of gender on asthma in childhood and adolescence: a GA(2)LEN review		ALLERGY	adolescence; asthma; child; GA(2)LEN; gender	BODY-MASS INDEX; RESPIRATORY SYMPTOMS; SEX-DIFFERENCES; LUNG-FUNCTION; BIRTH COHORT; BRONCHIAL RESPONSIVENESS; EMERGENCY-DEPARTMENT; DIAGNOSED ASTHMA; SWISS CHILDREN; RISK-FACTORS	A number of studies have shown gender differences in the prevalence of wheeze and asthma. The aim of this review was to examine published results on gender differences in childhood and adolescent asthma incidence and prevalence, define current concepts and to identify new research needs. A Medline search was performed with the search words (gender OR sex) AND (child OR childhood OR adolescence) AND (asthma). Articles that reported on abscence or prescence of gender differences in asthma were included and reviewed, and cross-references were checked. Boys are consistently reported to have more prevalent wheeze and asthma than girls. In adolescence, the pattern changes and onset of wheeze is more prevalent in females than males. Asthma, after childhood, is more severe in females than in males, and is underdiagnosed and undertreated in female adolescents. Possible explanations for this switch around puberty in the gender susceptibility to develop asthma include hormonal changes and gender-specific differences in environmental exposures. This aspect needs consideration of the doctors and allergists who diagnose and treat asthmatic individuals. In conclusion, sex hormones are likely to play an important role in the development and outcome of the allergic immune response and asthma in particular. By obtaining functional data from appropriate models, the exact underlying mechanisms can be unravelled. To examine the effect of gender-specific differences in environmental exposures and changes of asthma prevalence and severity in puberty, larger populations may need to be investigated.	54	228	2008	11	10.1111/j.1398-9995.2007.01524.x	Allergy; Immunology
Prostaglandin D-2 is a potent chemoattractant for human eosinophils that acts via a novel DIP receptor. Prostaglandin D-2 (PGD(2)) is released following exposure of asthmatics to allergen and acts via the adenylyl cyclase-coupled receptor for PGD(2) (DID receptor). In this study, it is reported that human eosinophils possess this receptor, which would be expected to inhibit their activation. In contrast, it was found that prostaglandin D-2 is a potent stimulator of eosinophil chemotaxis, actin polymerization, CD11b expression, and L-selectin shedding. These responses are specific for eosinophils, as neutrophils display little or no response to prostaglandin D-2 They were not due to interaction with receptors for other prostanoids, as prostaglandins E-2 and F-2 alpha, U46619 (a thromboxane A(2) analogue), and carbaprostacyclin (a prostacyclin analogue) displayed little or no activity. Furthermore, they were not shared by the selective DID receptor agonist BW245C and were not prevented by the selective DID receptor antagonist BWA868C, indicating that they were not mediated by DID receptors. In contrast, the prostaglandin D2 metabolite 13,14-dihydro-15-oxoprostaglandin D-2 induced eosinophil activation but did not stimulate DID receptor-mediated adenosine 3 ' ,5 ' -cyclic monophosphate (cAMP) formation. These results indicate that in addition to the classic inhibitory DID, receptor, eosinophils possess a second, novel DP2 receptor that is associated with PGD(2)-induced cell activation. These 2 receptors appear to interact to regulate eosinophil responses to PGD(2), as blockade of DPI receptor-mediated cAMP production by BWA868C resulted in enhanced DP2 receptor-mediated stimulation of CD11b expression. The balance between DPI and DP2 receptors could determine the degree to which prostaglandin D-2 can activate eosinophils and may play a role in eosinophil recruitment in asthma.. 5-oxo-6,8,11,14-eicosatetraenoic acid| prostanoid receptors| human neutrophils| l-selectin| human-platelets| human airways| d synthetase| mast-cells| inhibition| expression.	SEP 15-2001	5-oxo-6,8,11,14-eicosatetraenoic acid| prostanoid receptors| human neutrophils| l-selectin| human-platelets| human airways| d synthetase| mast-cells| inhibition| expression	Monneret, G; Gravel, S; Diamond, M; Rokach, J; Powell, WS	Prostaglandin D-2 is a potent chemoattractant for human eosinophils that acts via a novel DIP receptor		BLOOD		5-OXO-6,8,11,14-EICOSATETRAENOIC ACID; PROSTANOID RECEPTORS; HUMAN NEUTROPHILS; L-SELECTIN; HUMAN-PLATELETS; HUMAN AIRWAYS; D SYNTHETASE; MAST-CELLS; INHIBITION; EXPRESSION	Prostaglandin D-2 (PGD(2)) is released following exposure of asthmatics to allergen and acts via the adenylyl cyclase-coupled receptor for PGD(2) (DID receptor). In this study, it is reported that human eosinophils possess this receptor, which would be expected to inhibit their activation. In contrast, it was found that prostaglandin D-2 is a potent stimulator of eosinophil chemotaxis, actin polymerization, CD11b expression, and L-selectin shedding. These responses are specific for eosinophils, as neutrophils display little or no response to prostaglandin D-2 They were not due to interaction with receptors for other prostanoids, as prostaglandins E-2 and F-2 alpha, U46619 (a thromboxane A(2) analogue), and carbaprostacyclin (a prostacyclin analogue) displayed little or no activity. Furthermore, they were not shared by the selective DID receptor agonist BW245C and were not prevented by the selective DID receptor antagonist BWA868C, indicating that they were not mediated by DID receptors. In contrast, the prostaglandin D2 metabolite 13,14-dihydro-15-oxoprostaglandin D-2 induced eosinophil activation but did not stimulate DID receptor-mediated adenosine 3 ' ,5 ' -cyclic monophosphate (cAMP) formation. These results indicate that in addition to the classic inhibitory DID, receptor, eosinophils possess a second, novel DP2 receptor that is associated with PGD(2)-induced cell activation. These 2 receptors appear to interact to regulate eosinophil responses to PGD(2), as blockade of DPI receptor-mediated cAMP production by BWA868C resulted in enhanced DP2 receptor-mediated stimulation of CD11b expression. The balance between DPI and DP2 receptors could determine the degree to which prostaglandin D-2 can activate eosinophils and may play a role in eosinophil recruitment in asthma.	53	228	2001	7	10.1182/blood.V98.6.1942	Hematology
Association of low-level ozone and fine particles with respiratory symptoms in children with asthma. Context Exposure to ozone and particulate matter of 2.5 mum or less (PM2.5) in air at levels above current US Environmental Protection Agency (EPA) standards is a risk factor for respiratory symptoms in children with asthma. Objective To examine simultaneous effects of ozone and PM2.5 at levels below EPA standards on daily respiratory symptoms and rescue medication use among children with asthma. Design, Setting, and Participants Daily respiratory symptoms and medication use were examined prospectively for 271 children younger than 12 years with physician-diagnosed, active asthma residing in southern New England. Exposure to ambient concentrations of ozone and PM2.5 from April 1 through September 30, 2001, was assessed using ozone (peak 1-hour and 8-hour) and 24-hour PM2.5. Logistic regression analyses using generalized estimating equations were performed separately for maintenance medication users (n=130) and nonusers (n=141). Associations between pollutants (adjusted for temperature, controlling for same- and previous-day levels) and respiratory symptoms and use of rescue medication were evaluated. Main Outcome Measures Respiratory symptoms and rescue medication use recorded on calendars by subjects' mothers. Results Mean (SD) levels were 59 (19) ppb (1-hour average) and 51 (16) ppb (8-hour average) for ozone and 13 (8) mug/m(3) for PM2.5. In copollutant models, ozone level but not PM2.5 was significantly associated with respiratory symptoms and rescue medication use among children using maintenance medication; a 50-ppb increase in 1-hour ozone was associated with increased likelihood of wheeze (by 35%) and chest tightness (by 47%). The highest levels of ozone (1-hour or 8-hour averages) were associated with increased shortness of breath and rescue medication use. No significant, exposure-dependent associations were observed for any outcome by any pollutant among children who did not use maintenance medication. Conclusion Asthmatic children using maintenance medication are particularly vulnerable to ozone, controlling for exposure to fine particles, at levels below EPA standards.. african-american children| air-pollution| mexico-city| medication use| ambient ozone| 1st year| particulate| exposure| summer| health.	OCT 8-2003	african-american children| air-pollution| mexico-city| medication use| ambient ozone| 1st year| particulate| exposure| summer| health	Gent, JF; Triche, EW; Holford, TR; Belanger, K; Bracken, MB; Beckett, WS; Leaderer, BP	Association of low-level ozone and fine particles with respiratory symptoms in children with asthma		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		AFRICAN-AMERICAN CHILDREN; AIR-POLLUTION; MEXICO-CITY; MEDICATION USE; AMBIENT OZONE; 1ST YEAR; PARTICULATE; EXPOSURE; SUMMER; HEALTH	Context Exposure to ozone and particulate matter of 2.5 mum or less (PM2.5) in air at levels above current US Environmental Protection Agency (EPA) standards is a risk factor for respiratory symptoms in children with asthma. Objective To examine simultaneous effects of ozone and PM2.5 at levels below EPA standards on daily respiratory symptoms and rescue medication use among children with asthma. Design, Setting, and Participants Daily respiratory symptoms and medication use were examined prospectively for 271 children younger than 12 years with physician-diagnosed, active asthma residing in southern New England. Exposure to ambient concentrations of ozone and PM2.5 from April 1 through September 30, 2001, was assessed using ozone (peak 1-hour and 8-hour) and 24-hour PM2.5. Logistic regression analyses using generalized estimating equations were performed separately for maintenance medication users (n=130) and nonusers (n=141). Associations between pollutants (adjusted for temperature, controlling for same- and previous-day levels) and respiratory symptoms and use of rescue medication were evaluated. Main Outcome Measures Respiratory symptoms and rescue medication use recorded on calendars by subjects' mothers. Results Mean (SD) levels were 59 (19) ppb (1-hour average) and 51 (16) ppb (8-hour average) for ozone and 13 (8) mug/m(3) for PM2.5. In copollutant models, ozone level but not PM2.5 was significantly associated with respiratory symptoms and rescue medication use among children using maintenance medication; a 50-ppb increase in 1-hour ozone was associated with increased likelihood of wheeze (by 35%) and chest tightness (by 47%). The highest levels of ozone (1-hour or 8-hour averages) were associated with increased shortness of breath and rescue medication use. No significant, exposure-dependent associations were observed for any outcome by any pollutant among children who did not use maintenance medication. Conclusion Asthmatic children using maintenance medication are particularly vulnerable to ozone, controlling for exposure to fine particles, at levels below EPA standards.	24	227	2003	9	10.1001/jama.290.14.1859	General & Internal Medicine
A regression-based method for mapping traffic-related air pollution: application and testing in four contrasting urban environments. Accurate, high-resolution maps of traffic-related air pollution are needed both as a basis for assessing exposures as part of epidemiological studies, and to inform urban air-quality policy and traffic management. This paper assesses the use of a GIS-based, regression mapping technique to model spatial patterns of traffic-related air pollution. The model - developed using data from 80 passive sampler sites in Huddersfield, as part of the SAVIAH (Small Area Variations in Air Quality and Health) project - uses data on traffic flows and land cover in the 300-m buffer zone around each site, and altitude of the site, as predictors of NO, concentrations. It was tested here by application in four urban areas in the UK: Huddersfield (for the year following that used for initial model development), Sheffield, Northampton, and part of London. In each case, a GIS was built in ArcInfo, integrating relevant data on road traffic, urban land use and topography. Monitoring of NO2 was undertaken using replicate passive samplers (in London, data were obtained from surveys carried out as part of the London network). In Huddersfield, Sheffield and Northampton, the model was first calibrated by comparing modelled results with monitored NO2 concentrations at 10 randomly selected sites; the calibrated model was then validated against data from a further 10-28 sites. In London, where data for only 11 sites were available, validation was not undertaken. Results showed that the model performed well in all cases. After local calibration, the model gave estimates of mean annual NO2 concentrations within a factor of 1.5 of the actual mean (approx. 70-90%) of the time and within a factor of 2 between 70 and 100% of the time. r(2) values between modelled and observed concentrations are in the range of 0.58-0.76. These results are comparable to those achieved by more sophisticated dispersion models. The model also has several advantages over dispersion modelling. It is able, for example, to provide high-resolution maps across a whole urban area without the need to interpolate between receptor points. It also offers substantially reduced costs and processing times compared to formal dispersion modelling. It is concluded that the model might thus be used as a means of mapping long-term air pollution concentrations either in support of local authority air-quality management strategies, or in epidemiological studies. (C) 2000 Elsevier Science B.V. All rights reserved.. air pollution| exposure assessment| road traffic| gis| mapping|nitrogen-dioxide concentrations| respiratory health| united-kingdom| children| asthma| gis| samplers| models| roads.	MAY 15-2000	air pollution| exposure assessment| road traffic| gis| mapping|nitrogen-dioxide concentrations| respiratory health| united-kingdom| children| asthma| gis| samplers| models| roads	Briggs, DJ; de Hoogh, C; Guiliver, J; Wills, J; Elliott, P; Kingham, S; Smallbone, K	A regression-based method for mapping traffic-related air pollution: application and testing in four contrasting urban environments		SCIENCE OF THE TOTAL ENVIRONMENT	air pollution; exposure assessment; road traffic; GIS; mapping	NITROGEN-DIOXIDE CONCENTRATIONS; RESPIRATORY HEALTH; UNITED-KINGDOM; CHILDREN; ASTHMA; GIS; SAMPLERS; MODELS; ROADS	Accurate, high-resolution maps of traffic-related air pollution are needed both as a basis for assessing exposures as part of epidemiological studies, and to inform urban air-quality policy and traffic management. This paper assesses the use of a GIS-based, regression mapping technique to model spatial patterns of traffic-related air pollution. The model - developed using data from 80 passive sampler sites in Huddersfield, as part of the SAVIAH (Small Area Variations in Air Quality and Health) project - uses data on traffic flows and land cover in the 300-m buffer zone around each site, and altitude of the site, as predictors of NO, concentrations. It was tested here by application in four urban areas in the UK: Huddersfield (for the year following that used for initial model development), Sheffield, Northampton, and part of London. In each case, a GIS was built in ArcInfo, integrating relevant data on road traffic, urban land use and topography. Monitoring of NO2 was undertaken using replicate passive samplers (in London, data were obtained from surveys carried out as part of the London network). In Huddersfield, Sheffield and Northampton, the model was first calibrated by comparing modelled results with monitored NO2 concentrations at 10 randomly selected sites; the calibrated model was then validated against data from a further 10-28 sites. In London, where data for only 11 sites were available, validation was not undertaken. Results showed that the model performed well in all cases. After local calibration, the model gave estimates of mean annual NO2 concentrations within a factor of 1.5 of the actual mean (approx. 70-90%) of the time and within a factor of 2 between 70 and 100% of the time. r(2) values between modelled and observed concentrations are in the range of 0.58-0.76. These results are comparable to those achieved by more sophisticated dispersion models. The model also has several advantages over dispersion modelling. It is able, for example, to provide high-resolution maps across a whole urban area without the need to interpolate between receptor points. It also offers substantially reduced costs and processing times compared to formal dispersion modelling. It is concluded that the model might thus be used as a means of mapping long-term air pollution concentrations either in support of local authority air-quality management strategies, or in epidemiological studies. (C) 2000 Elsevier Science B.V. All rights reserved.	51	227	2000	17	10.1016/S0048-9697(00)00429-0	Environmental Sciences & Ecology
The environmental predictors of allergic disease. The prevalence of allergic diseases has been on the rise for the last 200 years, when hay fever, an easy and obvious-to-recognize illness, was virtually unknown in Europe and North America. Genetic factors are unlikely to explain these rapid increases, Among the potential environmental factors, exposure to ambient air pollution has been intensely debated, Besides passive smoking, which has convincingly been shown to increase the risk for asthma and bronchial hyperresponsiveness among exposed children, the evidence to suggest that outdoor pollution to sulfur dioxide, particulate matter, diesel exhaust, and ozone is causally related with the inception of allergic diseases is poor. Rather, factors associated with the lifestyle of populations or families, such as socioeconomic status, allergen exposure, sibship size, early childhood infections, dietary habits, and growing up in anthroposophic families or a farming environment, may prove to be of greater relevance. The future challenge is to tackle the complex interplay between environmental factors and genetic determinants that will eventually contribute to a better understanding and to better prevention strategies for such multifactorial conditions as asthma and allergies.. allergy| environment| epidemiology| atopy| asthma|respiratory syncytial virus| skin-test reactivity| diesel exhaust particles| serum ige levels| risk-factors| pulmonary-function| atopic disease| ozone exposure| air-pollution| hay-fever.	JAN-2000	allergy| environment| epidemiology| atopy| asthma|respiratory syncytial virus| skin-test reactivity| diesel exhaust particles| serum ige levels| risk-factors| pulmonary-function| atopic disease| ozone exposure| air-pollution| hay-fever	von Mutius, E	The environmental predictors of allergic disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; environment; epidemiology; atopy; asthma	RESPIRATORY SYNCYTIAL VIRUS; SKIN-TEST REACTIVITY; DIESEL EXHAUST PARTICLES; SERUM IGE LEVELS; RISK-FACTORS; PULMONARY-FUNCTION; ATOPIC DISEASE; OZONE EXPOSURE; AIR-POLLUTION; HAY-FEVER	The prevalence of allergic diseases has been on the rise for the last 200 years, when hay fever, an easy and obvious-to-recognize illness, was virtually unknown in Europe and North America. Genetic factors are unlikely to explain these rapid increases, Among the potential environmental factors, exposure to ambient air pollution has been intensely debated, Besides passive smoking, which has convincingly been shown to increase the risk for asthma and bronchial hyperresponsiveness among exposed children, the evidence to suggest that outdoor pollution to sulfur dioxide, particulate matter, diesel exhaust, and ozone is causally related with the inception of allergic diseases is poor. Rather, factors associated with the lifestyle of populations or families, such as socioeconomic status, allergen exposure, sibship size, early childhood infections, dietary habits, and growing up in anthroposophic families or a farming environment, may prove to be of greater relevance. The future challenge is to tackle the complex interplay between environmental factors and genetic determinants that will eventually contribute to a better understanding and to better prevention strategies for such multifactorial conditions as asthma and allergies.	124	227	2000	11	10.1016/S0091-6749(00)90171-4	Allergy; Immunology
TRPA1 is a major oxidant sensor in murine airway sensory neurons. Sensory neurons in the airways are finely tuned to respond to reactive chemicals threatening airway function and integrity. Nasal trigeminal nerve endings are particularly sensitive to oxidants formed in polluted air and during oxidative stress as well as to chlorine, which is frequently released in industrial and domestic accidents. Oxidant activation of airway neurons induces respiratory depression, nasal obstruction, sneezing, cough, and pain. While normally protective, chemosensory airway reflexes can provoke severe complications in patients affected by inflammatory airway conditions like rhinitis and asthma. Here, we showed that both hypochlorite, the oxidizing mediator of chlorine, and hydrogen peroxide, a reactive oxygen species, activated Ca2+ influx and membrane currents in an oxidant-sensitive subpopulation of chemosensory neurons. These responses were absent in neurons from mice lacking TRPA1, an ion channel of the transient receptor potential (TRP) gene family. TRPA1 channels were strongly activated by hypochlorite and hydrogen peroxide in primary sensory neurons and heterologous cells. In tests of respiratory function, Trpa1(-/-) mice displayed profound deficiencies in hypochlorite- and hydrogen peroxide-induced respiratory depression as well as decreased oxidant-induced pain behavior. Our results indicate that TRPA1 is an oxidant sensor in sensory neurons, initiating neuronal excitation and subsequent physiological responses in vitro and in vivo.. sensing ion channels| gene-related peptide| airborne chemicals| chlorine inhalation| irritation response| hypochlorous acid| longitudinal distribution| respiratory responses| covalent modification| oxidative stress.	MAY-2008	sensing ion channels| gene-related peptide| airborne chemicals| chlorine inhalation| irritation response| hypochlorous acid| longitudinal distribution| respiratory responses| covalent modification| oxidative stress	Bessac, BF; Sivula, M; Von Hehn, CA; Escalera, J; Cohn, L; Jordt, SE	TRPA1 is a major oxidant sensor in murine airway sensory neurons		JOURNAL OF CLINICAL INVESTIGATION		SENSING ION CHANNELS; GENE-RELATED PEPTIDE; AIRBORNE CHEMICALS; CHLORINE INHALATION; IRRITATION RESPONSE; HYPOCHLOROUS ACID; LONGITUDINAL DISTRIBUTION; RESPIRATORY RESPONSES; COVALENT MODIFICATION; OXIDATIVE STRESS	Sensory neurons in the airways are finely tuned to respond to reactive chemicals threatening airway function and integrity. Nasal trigeminal nerve endings are particularly sensitive to oxidants formed in polluted air and during oxidative stress as well as to chlorine, which is frequently released in industrial and domestic accidents. Oxidant activation of airway neurons induces respiratory depression, nasal obstruction, sneezing, cough, and pain. While normally protective, chemosensory airway reflexes can provoke severe complications in patients affected by inflammatory airway conditions like rhinitis and asthma. Here, we showed that both hypochlorite, the oxidizing mediator of chlorine, and hydrogen peroxide, a reactive oxygen species, activated Ca2+ influx and membrane currents in an oxidant-sensitive subpopulation of chemosensory neurons. These responses were absent in neurons from mice lacking TRPA1, an ion channel of the transient receptor potential (TRP) gene family. TRPA1 channels were strongly activated by hypochlorite and hydrogen peroxide in primary sensory neurons and heterologous cells. In tests of respiratory function, Trpa1(-/-) mice displayed profound deficiencies in hypochlorite- and hydrogen peroxide-induced respiratory depression as well as decreased oxidant-induced pain behavior. Our results indicate that TRPA1 is an oxidant sensor in sensory neurons, initiating neuronal excitation and subsequent physiological responses in vitro and in vivo.	87	226	2008	12	10.1172/JCI34192	Research & Experimental Medicine
Titrating steroids on exhaled nitric oxide in children with asthma - A randomized controlled trial. Rationale: Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (F-ENO) is a marker of airway inflammation in asthma. Objective: We evaluated whether titrating steroids on F-ENO improved asthma management in children. Methods: Eighty-five children with atopic asthma, using inhaled steroids, were allocated to a F-ENO group (n = 39) in which treatment decisions were made on both F-ENO and symptoms, or to a symptom group (n = 46) treated on symptoms only. Children were seen eve 3 months over a 1-year period. Measurements: Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO was measured at all visits, and airway hyperresponsiveness and FEV1 were measured at the start and end of the study. Primary endpoint was cumulative steroid dose. Results: Changes in steroid dose from baseline did not differ between groups. In the F-ENO group, hyperresponsiveness improved more than in the symptom group (2.5 vs. 1.1 doubling dose, p = 0.04). FEV1 in the F-ENO group improved, and the change in FEV1 was not significantly different between groups. The F-ENO group had 8 severe exacerbations versus 18 in the symptom group. The change in symptom scores did not differ between groups. F-ENO increased in the symptom group; the change in F-ENO from baseline differed between groups (p = 0.02). Conclusion: In children with asthma, 1 year of steroid titration on F-ENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation.. airway hyperresponsiveness| corticosteroids| lung function| symptoms| treatment|airway inflammation| childhood asthma| bronchial hyperresponsiveness| longitudinal population| clinical remission| allergic-asthma| atopic asthma| lung-function| risk-factors| markers.	OCT 1-2005	airway hyperresponsiveness| corticosteroids| lung function| symptoms| treatment|airway inflammation| childhood asthma| bronchial hyperresponsiveness| longitudinal population| clinical remission| allergic-asthma| atopic asthma| lung-function| risk-factors| markers	Pijnenburg, MW; Bakker, EM; Hop, WC; De Jongste, JC	Titrating steroids on exhaled nitric oxide in children with asthma - A randomized controlled trial		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	airway hyperresponsiveness; corticosteroids; lung function; symptoms; treatment	AIRWAY INFLAMMATION; CHILDHOOD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS; LONGITUDINAL POPULATION; CLINICAL REMISSION; ALLERGIC-ASTHMA; ATOPIC ASTHMA; LUNG-FUNCTION; RISK-FACTORS; MARKERS	Rationale: Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (F-ENO) is a marker of airway inflammation in asthma. Objective: We evaluated whether titrating steroids on F-ENO improved asthma management in children. Methods: Eighty-five children with atopic asthma, using inhaled steroids, were allocated to a F-ENO group (n = 39) in which treatment decisions were made on both F-ENO and symptoms, or to a symptom group (n = 46) treated on symptoms only. Children were seen eve 3 months over a 1-year period. Measurements: Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO was measured at all visits, and airway hyperresponsiveness and FEV1 were measured at the start and end of the study. Primary endpoint was cumulative steroid dose. Results: Changes in steroid dose from baseline did not differ between groups. In the F-ENO group, hyperresponsiveness improved more than in the symptom group (2.5 vs. 1.1 doubling dose, p = 0.04). FEV1 in the F-ENO group improved, and the change in FEV1 was not significantly different between groups. The F-ENO group had 8 severe exacerbations versus 18 in the symptom group. The change in symptom scores did not differ between groups. F-ENO increased in the symptom group; the change in F-ENO from baseline differed between groups (p = 0.02). Conclusion: In children with asthma, 1 year of steroid titration on F-ENO did not result in higher steroid doses and did improve airway hyperresponsiveness and inflammation.	41	225	2005	6	10.1164/rccm.200503-458OC	General & Internal Medicine; Respiratory System
Phase II of the international study of asthma and allergies in childhood (ISAAC II): rationale and methods. International comparative studies, investigating whether disease incidence or prevalence rates differ between populations and, if so, which factors explain the observed differences, have made important contributions to the understanding of disease aetiology in many areas. In Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence rates of symptoms of asthma, allergic rhinitis and atopic eczema in 13-14-yr-olds, assessed by standardised questionnaires, were found to differ >20-fold between the 155 study centres around the world. Phase II of ISAAC aims to identify determinants of these differences by studying informative populations. A detailed study protocol was developed for use in community-based random samples of children aged 9-11 yrs. The study modules include standardised questionnaires with detailed questions on the occurrence and severity of symptoms of asthma, allergic rhinitis and atopic eczema, their clinical management, and a broad range of previous and current exposure conditions. In addition, standardised protocols were applied for examination of flexural dermatitis, skin-prick testing, bronchial challenge with hypertonic saline, blood sampling for immunoglobulin E analyses and genotyping, and dust sampling for assessment of indoor exposures to allergens and endotoxin. To date, ISAAC II field work had been completed or started in 30 study centres in 22 countries. The majority of centres are in countries that participated in International Study of Asthma and Allergies in Childhood Phase I and reflect almost the full range of the observed variability in Phase I prevalence rates.. asthma| childhood| eczema| epidemiology| international study of asthma and allergies| in childhood phase ii| rhinitis|respiratory-health-survey| worldwide variations| blood-pressure| atopic eczema| prevalence| symptoms| children| rhinoconjunctivitis.	SEP-2004	asthma| childhood| eczema| epidemiology| international study of asthma and allergies| in childhood phase ii| rhinitis|respiratory-health-survey| worldwide variations| blood-pressure| atopic eczema| prevalence| symptoms| children| rhinoconjunctivitis	Weiland, SK; Bjorksten, B; Brunekreef, B; Cookson, WOC; von Mutius, E; Strachan, DP	Phase II of the international study of asthma and allergies in childhood (ISAAC II): rationale and methods		EUROPEAN RESPIRATORY JOURNAL	asthma; childhood; eczema; epidemiology; international study of asthma and allergies; in childhood phase II; rhinitis	RESPIRATORY-HEALTH-SURVEY; WORLDWIDE VARIATIONS; BLOOD-PRESSURE; ATOPIC ECZEMA; PREVALENCE; SYMPTOMS; CHILDREN; RHINOCONJUNCTIVITIS	International comparative studies, investigating whether disease incidence or prevalence rates differ between populations and, if so, which factors explain the observed differences, have made important contributions to the understanding of disease aetiology in many areas. In Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence rates of symptoms of asthma, allergic rhinitis and atopic eczema in 13-14-yr-olds, assessed by standardised questionnaires, were found to differ >20-fold between the 155 study centres around the world. Phase II of ISAAC aims to identify determinants of these differences by studying informative populations. A detailed study protocol was developed for use in community-based random samples of children aged 9-11 yrs. The study modules include standardised questionnaires with detailed questions on the occurrence and severity of symptoms of asthma, allergic rhinitis and atopic eczema, their clinical management, and a broad range of previous and current exposure conditions. In addition, standardised protocols were applied for examination of flexural dermatitis, skin-prick testing, bronchial challenge with hypertonic saline, blood sampling for immunoglobulin E analyses and genotyping, and dust sampling for assessment of indoor exposures to allergens and endotoxin. To date, ISAAC II field work had been completed or started in 30 study centres in 22 countries. The majority of centres are in countries that participated in International Study of Asthma and Allergies in Childhood Phase I and reflect almost the full range of the observed variability in Phase I prevalence rates.	25	225	2004	7	10.1183/09031936.04.00090303	Respiratory System
Epithelium dysfunction in asthma. Although asthma is an inflammatory disorder of the conducting airways involving T(H)2-type T cells, there is increasing evidence for an important role played by the epithelium in orchestrating the inflammatory response by interacting with multiple environmental factors to produce a chronic wound scenario involving tissue injury and aberrant repair. Part of this abnormal response is the consequence of impaired barrier function caused by a primary disruption of epithelial tight junctions that allows inhaled substances to pass more easily into the airway wall to interact with immune and inflammatory cells. Aberrant communication between the damaged and stressed epithelium leads to the generation of growth factors that interact with the underlying mesenchyme to promote airway remodeling responses and a more chronic and persistent inflammatory phenotype. Disordered epithelial function with reduced antioxidant defense and impaired capacity to produce primary IFNs may also account for asthmatic susceptibility to air pollution and respiratory virus infection, respectively. Considering asthma as a disease of impaired barrier function opens new opportunities for therapeutic intervention or prevention by agents that could increase the airways resistance to the inhaled environment rather than suppressing the immune or inflammatory response.. asthma| environment| epithelium| epithelial mesenchymal trophic unit| airway remodeling| origins of asthma| progression of asthma| tight junctions| impaired barrier function|reticular basement-membrane| resolution computed-tomography| obstructive pulmonary-disease| allergic airway inflammation| lung-transplant recipients| goblet cell hyperplasia| growth-factor receptor| killer t-cells| bronchial epithelium| eosinophilic bronchitis.	DEC-2007	asthma| environment| epithelium| epithelial mesenchymal trophic unit| airway remodeling| origins of asthma| progression of asthma| tight junctions| impaired barrier function|reticular basement-membrane| resolution computed-tomography| obstructive pulmonary-disease| allergic airway inflammation| lung-transplant recipients| goblet cell hyperplasia| growth-factor receptor| killer t-cells| bronchial epithelium| eosinophilic bronchitis	Holgate, ST	Epithelium dysfunction in asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; environment; epithelium; epithelial mesenchymal trophic unit; airway remodeling; origins of asthma; progression of asthma; tight junctions; impaired barrier function	RETICULAR BASEMENT-MEMBRANE; RESOLUTION COMPUTED-TOMOGRAPHY; OBSTRUCTIVE PULMONARY-DISEASE; ALLERGIC AIRWAY INFLAMMATION; LUNG-TRANSPLANT RECIPIENTS; GOBLET CELL HYPERPLASIA; GROWTH-FACTOR RECEPTOR; KILLER T-CELLS; BRONCHIAL EPITHELIUM; EOSINOPHILIC BRONCHITIS	Although asthma is an inflammatory disorder of the conducting airways involving T(H)2-type T cells, there is increasing evidence for an important role played by the epithelium in orchestrating the inflammatory response by interacting with multiple environmental factors to produce a chronic wound scenario involving tissue injury and aberrant repair. Part of this abnormal response is the consequence of impaired barrier function caused by a primary disruption of epithelial tight junctions that allows inhaled substances to pass more easily into the airway wall to interact with immune and inflammatory cells. Aberrant communication between the damaged and stressed epithelium leads to the generation of growth factors that interact with the underlying mesenchyme to promote airway remodeling responses and a more chronic and persistent inflammatory phenotype. Disordered epithelial function with reduced antioxidant defense and impaired capacity to produce primary IFNs may also account for asthmatic susceptibility to air pollution and respiratory virus infection, respectively. Considering asthma as a disease of impaired barrier function opens new opportunities for therapeutic intervention or prevention by agents that could increase the airways resistance to the inhaled environment rather than suppressing the immune or inflammatory response.	130	224	2007	14	10.1016/j.jaci.2007.10.025	Allergy; Immunology
Mechanisms of airway hyperresponsiveness. Airway hyperresponsiveness (AHR) to direct (histamine and methacholine) and indirect (exercise, cold air, hyperventilation, AMP) challenges is a universal and defining feature of asthma. One component of AHR is transient or inducible and occurs after allergen exposure, for example, and improves occasionally rapidly after inhaled corticosteroids or environmental control. This transient airway hyperresponsiveness is more marked to the indirect stimuli. There are convincing data linking this component of AHR to airway inflammation; however, the precise mechanisms linking airway inflammation and hyperresponsiveness of the airway smooth muscle are not clear. The other component of AHR is more persistent and is relatively refractory to environmental control and inhaled corticosteroids. This is likely secondary to structural airway changes, which are collectively referred to as airway remodeling, and which are a result of the chronic (rather than the acute) effects of airway inflammation. This persistent AHR is best reflected by airway hyperresponsiveness to direct stimuli such as methacholine. The mechanisms are also uncertain, but reduced airway caliber, increased airway wall thickness, increased airway smooth muscle mass, and perhaps contractility likely all play a role.. asthma| airway hyperresponsiveness| airway inflammation| airway smooth muscle|late asthmatic response| indirect bronchial hyperresponsiveness| allergen-induced increases| smooth-muscle| monoclonal-antibody| inhaled budesonide| mast-cells| adenosine 5'-monophosphate| bronchoalveolar lavage| toluene diisocyanate.	SEP-2006	asthma| airway hyperresponsiveness| airway inflammation| airway smooth muscle|late asthmatic response| indirect bronchial hyperresponsiveness| allergen-induced increases| smooth-muscle| monoclonal-antibody| inhaled budesonide| mast-cells| adenosine 5'-monophosphate| bronchoalveolar lavage| toluene diisocyanate	Cockcroft, DW; Davis, BE	Mechanisms of airway hyperresponsiveness		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; airway hyperresponsiveness; airway inflammation; airway smooth muscle	LATE ASTHMATIC RESPONSE; INDIRECT BRONCHIAL HYPERRESPONSIVENESS; ALLERGEN-INDUCED INCREASES; SMOOTH-MUSCLE; MONOCLONAL-ANTIBODY; INHALED BUDESONIDE; MAST-CELLS; ADENOSINE 5'-MONOPHOSPHATE; BRONCHOALVEOLAR LAVAGE; TOLUENE DIISOCYANATE	Airway hyperresponsiveness (AHR) to direct (histamine and methacholine) and indirect (exercise, cold air, hyperventilation, AMP) challenges is a universal and defining feature of asthma. One component of AHR is transient or inducible and occurs after allergen exposure, for example, and improves occasionally rapidly after inhaled corticosteroids or environmental control. This transient airway hyperresponsiveness is more marked to the indirect stimuli. There are convincing data linking this component of AHR to airway inflammation; however, the precise mechanisms linking airway inflammation and hyperresponsiveness of the airway smooth muscle are not clear. The other component of AHR is more persistent and is relatively refractory to environmental control and inhaled corticosteroids. This is likely secondary to structural airway changes, which are collectively referred to as airway remodeling, and which are a result of the chronic (rather than the acute) effects of airway inflammation. This persistent AHR is best reflected by airway hyperresponsiveness to direct stimuli such as methacholine. The mechanisms are also uncertain, but reduced airway caliber, increased airway wall thickness, increased airway smooth muscle mass, and perhaps contractility likely all play a role.	130	224	2006	9	10.1016/j.jaci.2006.07.012	Allergy; Immunology
IgG4 breaking the rules. Immunoglobulin G4 (IgG4) antibodies have been known for some time to be functionally monovalent. Recently, the structural basis for this monovalency has been elucidated: the in vivo exchange of IgG half-molecules (one H-plus one L-chain) among IgG4. This process results in bispecific antibodies that in most situations will behave as functionally monovalent antibodies. The structural basis for the abnormal behaviour of IgG4 seems to be largely the result of a single amino acid change relative to human IgG1: the change of a proline in core hinge of IgG1 to serine. This results in a marked shift in the equilibrium between interchain disulphide bridges and intrachain disulphide bridges, which for IgG4 results in 25-75% absence of a covalent interaction between the H-chains. Because of strong non-covalent interactions between the CH3 domains (and possibly also between the CH1 domain and the trans-CH2 domain) IgG4 is a stable four-chain molecule and does not easily exchange half-molecules under standard physiological conditions in vitro. We postulate that the exchange is catalysed in vivo by protein disulphide isomerase (PDI) and/or FcRn (the major histocompatibility complex (MHC)-related Fc receptor) during transit of IgG4 in the endosomal pathway in endothelial cells. Because IgG4 is predominantly expressed under conditions of chronic antigen exposure, the biological relevance of this exchange of half-molecules is that it generates antibodies that are unable to form large immune complexes and therefore have a low potential for inducing immune inflammation. In contrast to monovalent immunoglobulin fragments, these scrambled immunoglobulins have a normal half-life. The significance of the ensuing bispecificity needs further evaluation, because thus will be relevant only in situations where high IgG4 responses are found to two unrelated antigens that happen to be present in the body at the same time and place. In this context the significance of IgG4 autoreactivity might have to be re-evaluated. The main function of IgG4, however, is presumably to interfere with immune inflammation induced by complement-fixing antibodies, or, in the case of helminth infection or allergy, by IgE antibodies.. facilitated allergen presentation| hinge region| complement activation| blocking antibody| serologic aspects| human filariasis| immunoglobulin-g| plasma-membrane| disulfide bonds| atopic disease.	JAN-2002	facilitated allergen presentation| hinge region| complement activation| blocking antibody| serologic aspects| human filariasis| immunoglobulin-g| plasma-membrane| disulfide bonds| atopic disease	Aalberse, RC; Schuurman, J	IgG4 breaking the rules		IMMUNOLOGY		FACILITATED ALLERGEN PRESENTATION; HINGE REGION; COMPLEMENT ACTIVATION; BLOCKING ANTIBODY; SEROLOGIC ASPECTS; HUMAN FILARIASIS; IMMUNOGLOBULIN-G; PLASMA-MEMBRANE; DISULFIDE BONDS; ATOPIC DISEASE	Immunoglobulin G4 (IgG4) antibodies have been known for some time to be functionally monovalent. Recently, the structural basis for this monovalency has been elucidated: the in vivo exchange of IgG half-molecules (one H-plus one L-chain) among IgG4. This process results in bispecific antibodies that in most situations will behave as functionally monovalent antibodies. The structural basis for the abnormal behaviour of IgG4 seems to be largely the result of a single amino acid change relative to human IgG1: the change of a proline in core hinge of IgG1 to serine. This results in a marked shift in the equilibrium between interchain disulphide bridges and intrachain disulphide bridges, which for IgG4 results in 25-75% absence of a covalent interaction between the H-chains. Because of strong non-covalent interactions between the CH3 domains (and possibly also between the CH1 domain and the trans-CH2 domain) IgG4 is a stable four-chain molecule and does not easily exchange half-molecules under standard physiological conditions in vitro. We postulate that the exchange is catalysed in vivo by protein disulphide isomerase (PDI) and/or FcRn (the major histocompatibility complex (MHC)-related Fc receptor) during transit of IgG4 in the endosomal pathway in endothelial cells. Because IgG4 is predominantly expressed under conditions of chronic antigen exposure, the biological relevance of this exchange of half-molecules is that it generates antibodies that are unable to form large immune complexes and therefore have a low potential for inducing immune inflammation. In contrast to monovalent immunoglobulin fragments, these scrambled immunoglobulins have a normal half-life. The significance of the ensuing bispecificity needs further evaluation, because thus will be relevant only in situations where high IgG4 responses are found to two unrelated antigens that happen to be present in the body at the same time and place. In this context the significance of IgG4 autoreactivity might have to be re-evaluated. The main function of IgG4, however, is presumably to interfere with immune inflammation induced by complement-fixing antibodies, or, in the case of helminth infection or allergy, by IgE antibodies.	65	224	2002	11	10.1046/j.0019-2805.2001.01341.x	Immunology
The role of nuclear factor-kappa B in pulmonary diseases. Nuclear factor-kappa B (NF-kappa B) is a family of DNA-binding protein factors that are required for transcription of most proinflammatory molecules, including adhesion molecules, enzymes, cytokines, and chemokines. NF-kappa B activation seems to be a key early event in a variety of cell and animal model systems developed to elucidate the pathobiology of lung diseases. The purpose of this short review is to describe what is known about the molecular biology of NF-kappa B and to review information that implicates NF-kappa B in the pathogenesis of lung disease, including ARDS, systemic inflammatory response syndrome, asthma, respiratory viral infections, occupational and environmental lung disease, and cystic fibrosis.. air pollution| ards| asbestosis| asthma| ozone| respiratory syncytial virus| rhinovirus| sepsis| silicosis|respiratory syncytial virus| bronchial epithelial-cells| dna-binding activity| transcription factors| alveolar macrophages| gene-expression| rat lung| pseudomonas-aeruginosa| interleukin-8 gene| oxidative stress.	MAY-2000	air pollution| ards| asbestosis| asthma| ozone| respiratory syncytial virus| rhinovirus| sepsis| silicosis|respiratory syncytial virus| bronchial epithelial-cells| dna-binding activity| transcription factors| alveolar macrophages| gene-expression| rat lung| pseudomonas-aeruginosa| interleukin-8 gene| oxidative stress	Christman, JW; Sadikot, RT; Blackwell, TS	The role of nuclear factor-kappa B in pulmonary diseases		CHEST	air pollution; ARDS; asbestosis; asthma; ozone; respiratory syncytial virus; rhinovirus; sepsis; silicosis	RESPIRATORY SYNCYTIAL VIRUS; BRONCHIAL EPITHELIAL-CELLS; DNA-BINDING ACTIVITY; TRANSCRIPTION FACTORS; ALVEOLAR MACROPHAGES; GENE-EXPRESSION; RAT LUNG; PSEUDOMONAS-AERUGINOSA; INTERLEUKIN-8 GENE; OXIDATIVE STRESS	Nuclear factor-kappa B (NF-kappa B) is a family of DNA-binding protein factors that are required for transcription of most proinflammatory molecules, including adhesion molecules, enzymes, cytokines, and chemokines. NF-kappa B activation seems to be a key early event in a variety of cell and animal model systems developed to elucidate the pathobiology of lung diseases. The purpose of this short review is to describe what is known about the molecular biology of NF-kappa B and to review information that implicates NF-kappa B in the pathogenesis of lung disease, including ARDS, systemic inflammatory response syndrome, asthma, respiratory viral infections, occupational and environmental lung disease, and cystic fibrosis.	45	224	2000	6	10.1378/chest.117.5.1482	General & Internal Medicine; Respiratory System
Update on glucocorticoid action and resistance. Extensive development of inhaled and oral glucocorticoids has resulted in highly potent molecules that have been optimized to target activity to the lung and minimize systemic exposure. These have proved highly effective for most asthmatic subjects, but despite these developments, there are a number of subjects with asthma who fail to respond to even high doses of inhaled or even oral glucocorticoids. Advances in delineating the fundamental mechanisms of glucocorticoid pharmacology, especially the concepts of transactivation and transrepression and cofactor recruitment, have resulted in better understanding of the molecular mechanisms whereby glucocorticoids suppress inflammation. The existence of multiple mechanisms underlying glucocorticoid insensitivity raises the possibility that this might indeed reflect different diseases with a common phenotype, and studies examining the efficacy of potential new agents should be targeted toward subgroups of patients with severe corticosteroid-resistant asthma who clearly require effective new drugs and other approaches to improved asthma control.. severe asthma| steroid resistance| glucocorticoid receptor| molecular mechanisms| future therapies|nf-kappa-b| obstructive pulmonary-disease| steroid-insensitive asthma| histone deacetylase activity| colony-stimulating factor| blood mononuclear-cells| pituitary-adrenal axis| receptor-beta-isoform| ligand-binding domain| necrosis-factor-alpha.	MAR-2006	severe asthma| steroid resistance| glucocorticoid receptor| molecular mechanisms| future therapies|nf-kappa-b| obstructive pulmonary-disease| steroid-insensitive asthma| histone deacetylase activity| colony-stimulating factor| blood mononuclear-cells| pituitary-adrenal axis| receptor-beta-isoform| ligand-binding domain| necrosis-factor-alpha	Ito, K; Chung, KF; Adcock, IM	Update on glucocorticoid action and resistance		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	severe asthma; steroid resistance; glucocorticoid receptor; molecular mechanisms; future therapies	NF-KAPPA-B; OBSTRUCTIVE PULMONARY-DISEASE; STEROID-INSENSITIVE ASTHMA; HISTONE DEACETYLASE ACTIVITY; COLONY-STIMULATING FACTOR; BLOOD MONONUCLEAR-CELLS; PITUITARY-ADRENAL AXIS; RECEPTOR-BETA-ISOFORM; LIGAND-BINDING DOMAIN; NECROSIS-FACTOR-ALPHA	Extensive development of inhaled and oral glucocorticoids has resulted in highly potent molecules that have been optimized to target activity to the lung and minimize systemic exposure. These have proved highly effective for most asthmatic subjects, but despite these developments, there are a number of subjects with asthma who fail to respond to even high doses of inhaled or even oral glucocorticoids. Advances in delineating the fundamental mechanisms of glucocorticoid pharmacology, especially the concepts of transactivation and transrepression and cofactor recruitment, have resulted in better understanding of the molecular mechanisms whereby glucocorticoids suppress inflammation. The existence of multiple mechanisms underlying glucocorticoid insensitivity raises the possibility that this might indeed reflect different diseases with a common phenotype, and studies examining the efficacy of potential new agents should be targeted toward subgroups of patients with severe corticosteroid-resistant asthma who clearly require effective new drugs and other approaches to improved asthma control.	234	223	2006	22	10.1016/j.jaci.2006.01.032	Allergy; Immunology
Oral tolerance and its relation to food hypersensitivities. The gastrointestinal tract is the largest immunologic organ in the body. It is constantly bombarded by a myriad of dietary proteins. Despite the extent of protein exposure, very few patients have food allergies because of development of oral tolerance to these antigens. Once proteins contact the intestinal surface, they are sampled by different cells and, depending on their characteristics, result in different responses. Antigens might be taken up by Microfold cells overlying Peyer's patches, dendritic cells, or epithelial cells. Different cells of the immune system participate in oral tolerance induction, with regulatory T cells being the most important. Several factors can influence tolerance induction. Some are antigen related, and others are inherent to the host. Disturbances at different steps in the path to oral tolerance have been described in food hypersensitivity. In this review we provide an overview of oral tolerance and cite data related to food hypersensitivity wherever evidence available.. oral tolerance| food allergy| food hypersensitivity| mucosal immunity| antigen uptake| intestine|regulatory t-cells| transforming growth factor-beta-1| transepithelial antigen transport| inflammatory-bowel-disease| myelin basic-protein| dendritic cells| peyers-patches| murine model| active suppression| immune tolerance.	JAN-2005	oral tolerance| food allergy| food hypersensitivity| mucosal immunity| antigen uptake| intestine|regulatory t-cells| transforming growth factor-beta-1| transepithelial antigen transport| inflammatory-bowel-disease| myelin basic-protein| dendritic cells| peyers-patches| murine model| active suppression| immune tolerance	Chehade, M; Mayer, L	Oral tolerance and its relation to food hypersensitivities		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	oral tolerance; food allergy; food hypersensitivity; mucosal immunity; antigen uptake; intestine	REGULATORY T-CELLS; TRANSFORMING GROWTH FACTOR-BETA-1; TRANSEPITHELIAL ANTIGEN TRANSPORT; INFLAMMATORY-BOWEL-DISEASE; MYELIN BASIC-PROTEIN; DENDRITIC CELLS; PEYERS-PATCHES; MURINE MODEL; ACTIVE SUPPRESSION; IMMUNE TOLERANCE	The gastrointestinal tract is the largest immunologic organ in the body. It is constantly bombarded by a myriad of dietary proteins. Despite the extent of protein exposure, very few patients have food allergies because of development of oral tolerance to these antigens. Once proteins contact the intestinal surface, they are sampled by different cells and, depending on their characteristics, result in different responses. Antigens might be taken up by Microfold cells overlying Peyer's patches, dendritic cells, or epithelial cells. Different cells of the immune system participate in oral tolerance induction, with regulatory T cells being the most important. Several factors can influence tolerance induction. Some are antigen related, and others are inherent to the host. Disturbances at different steps in the path to oral tolerance have been described in food hypersensitivity. In this review we provide an overview of oral tolerance and cite data related to food hypersensitivity wherever evidence available.	93	223	2005	10	10.1016/j.jaci.2004.11.008	Allergy; Immunology
The effect of chronic or intermittent hypoxia on cognition in childhood: A review of the evidence. Objective. A review of the evidence concerning the effect of chronic or intermittent hypoxia on cognition in childhood was performed by using both a systematic review of the literature and critical appraisal criteria of causality. Because of the significant impact of behavioral disorders such as attention-deficit/hyperactivity disorder on certain cognitive functions as well as academic achievement, the review also included articles that addressed behavioral outcomes. Methods. Both direct and indirect evidence were collected. A structured Medline search was conducted from the years 1966-2000 by using the OVID interface. Both English- and non - English- language citations were included. Significant articles identified by the reviewers up to 2003 were also included. To be included as direct evidence, an article needed to be an original report in a peer-reviewed journal with data on cognitive, behavioral, or academic outcomes in children up to 14 years old, with clinical conditions likely to be associated with exposure to chronic or intermittent hypoxia. Indirect evidence from other reviews and publications in closely related fields, including experimental studies in adults, was used to help formulate conclusions. Two reviewers screened abstracts and titles. Each article included as direct evidence received a structured evaluation by 2 reviewers. Adjudication of differences was performed by a group of 2 reviewers and a research consultant. After this review, tables of evidence were constructed that were used as the basis for group discussion and consensus development. Indirect evidence assigned by topic to specific reviewers was also presented as part of this process. A formal procedure was used to rank the studies by design strength. The critical appraisal criteria for causation described in Evidence Based Pediatrics and Child Health (Moyer V, Elliott E, Davis R, et al, eds. London, United Kingdom: BMJ Books; 2000: 46 - 55) were used to develop consensus on causality. Results. A total of 788 literature citations were screened. For the final analysis, 55 articles met the criteria for inclusion in the direct evidence. Of these, 43 (78.2%) reported an adverse effect. Of the 37 controlled studies, 31 (83.8%) reported an adverse effect. Adverse effects were noted at every level of arterial oxygen saturation and for exposure at every age level except for premature newborns. The studies were classified into 5 clinical categories: congenital heart disease (CHD), sleep-disordered breathing (SDB), asthma, chronic ventilatory impairment, and respiratory instability in infants. Two of these categories, CHD and SDB, which accounted for 42 (76.4%) of the included articles, fulfilled the Evidence Based Pediatrics and Child Health criteria for causation. The indirect evidence included 8 reviews, 1 meta-analysis, and 10 original reports covering the fields of adult anoxia, animal research, SDB in adults, natural and experimental high-altitude studies, perinatal hypoxic-ischemic encephalopathy, anemia, and carbon-monoxide poisoning. The studies of high-altitude and carbon-monoxide poisoning provided evidence for causality. Conclusions. Adverse impacts of chronic or intermittent hypoxia on development, behavior, and academic achievement have been reported in many well-designed and controlled studies in children with CHD and SDB as well as in a variety of experimental studies in adults. This should be taken into account in any situation that may expose children to hypoxia. Because adverse effects have been noted at even mild levels of oxygen desaturation, future research should include precisely defined data on exposure to all levels of desaturation.. hypoxia| cognition| development| behavior| academic achievement|obstructive sleep-apnea| congenital heart-disease| deficit-hyperactivity disorder| oxygen-saturation| term infants| respiratory instability| academic-performance| school performance| prospective cohort| motor development.	SEP-2004	hypoxia| cognition| development| behavior| academic achievement|obstructive sleep-apnea| congenital heart-disease| deficit-hyperactivity disorder| oxygen-saturation| term infants| respiratory instability| academic-performance| school performance| prospective cohort| motor development	Bass, JL; Corwin, M; Gozal, D; Moore, C; Nishida, H; Parker, S; Schonwald, A; Wilker, RE; Stehle, S; Kinane, TB	The effect of chronic or intermittent hypoxia on cognition in childhood: A review of the evidence		PEDIATRICS	hypoxia; cognition; development; behavior; academic achievement	OBSTRUCTIVE SLEEP-APNEA; CONGENITAL HEART-DISEASE; DEFICIT-HYPERACTIVITY DISORDER; OXYGEN-SATURATION; TERM INFANTS; RESPIRATORY INSTABILITY; ACADEMIC-PERFORMANCE; SCHOOL PERFORMANCE; PROSPECTIVE COHORT; MOTOR DEVELOPMENT	Objective. A review of the evidence concerning the effect of chronic or intermittent hypoxia on cognition in childhood was performed by using both a systematic review of the literature and critical appraisal criteria of causality. Because of the significant impact of behavioral disorders such as attention-deficit/hyperactivity disorder on certain cognitive functions as well as academic achievement, the review also included articles that addressed behavioral outcomes. Methods. Both direct and indirect evidence were collected. A structured Medline search was conducted from the years 1966-2000 by using the OVID interface. Both English- and non - English- language citations were included. Significant articles identified by the reviewers up to 2003 were also included. To be included as direct evidence, an article needed to be an original report in a peer-reviewed journal with data on cognitive, behavioral, or academic outcomes in children up to 14 years old, with clinical conditions likely to be associated with exposure to chronic or intermittent hypoxia. Indirect evidence from other reviews and publications in closely related fields, including experimental studies in adults, was used to help formulate conclusions. Two reviewers screened abstracts and titles. Each article included as direct evidence received a structured evaluation by 2 reviewers. Adjudication of differences was performed by a group of 2 reviewers and a research consultant. After this review, tables of evidence were constructed that were used as the basis for group discussion and consensus development. Indirect evidence assigned by topic to specific reviewers was also presented as part of this process. A formal procedure was used to rank the studies by design strength. The critical appraisal criteria for causation described in Evidence Based Pediatrics and Child Health (Moyer V, Elliott E, Davis R, et al, eds. London, United Kingdom: BMJ Books; 2000: 46 - 55) were used to develop consensus on causality. Results. A total of 788 literature citations were screened. For the final analysis, 55 articles met the criteria for inclusion in the direct evidence. Of these, 43 (78.2%) reported an adverse effect. Of the 37 controlled studies, 31 (83.8%) reported an adverse effect. Adverse effects were noted at every level of arterial oxygen saturation and for exposure at every age level except for premature newborns. The studies were classified into 5 clinical categories: congenital heart disease (CHD), sleep-disordered breathing (SDB), asthma, chronic ventilatory impairment, and respiratory instability in infants. Two of these categories, CHD and SDB, which accounted for 42 (76.4%) of the included articles, fulfilled the Evidence Based Pediatrics and Child Health criteria for causation. The indirect evidence included 8 reviews, 1 meta-analysis, and 10 original reports covering the fields of adult anoxia, animal research, SDB in adults, natural and experimental high-altitude studies, perinatal hypoxic-ischemic encephalopathy, anemia, and carbon-monoxide poisoning. The studies of high-altitude and carbon-monoxide poisoning provided evidence for causality. Conclusions. Adverse impacts of chronic or intermittent hypoxia on development, behavior, and academic achievement have been reported in many well-designed and controlled studies in children with CHD and SDB as well as in a variety of experimental studies in adults. This should be taken into account in any situation that may expose children to hypoxia. Because adverse effects have been noted at even mild levels of oxygen desaturation, future research should include precisely defined data on exposure to all levels of desaturation.	103	223	2004	12	10.1542/peds.2004-0227	Pediatrics
The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types. PM10 contains an ultrafine component, which is generally derived from combustion processes. This ultrafine fraction may be a factor in the increases in exacerbations of respiratory disease and deaths from cardiorespiratory causes associated with transient increases in levels of PM10. By using four different ultrafine particles (carbon black, cobalt, nickel, and titanium dioxide), we set out to determine the attributes of the ultrafine particle (surface area, chemical composition, particle number, or surface reactivity) that contribute most to its toxicity and proinflammatory effects both in vivo and in vitro. Instillation of 125 mug ultrafine carbon black (UFCB) and ultrafine cobalt (UFCo) particles induced a significant influx of neutrophils at both 4 and 18 h postinstillation. Accompanying the influx of neutrophils was an increase in macrophage inflammatory protein-2 (MIP-2) (at 4 h) and an increase in gamma-glutamyl transpeptidase (at 18 h) in bronchoalveolar lavage fluid (BAL). Ultrafine nickel (UFNi) did not induce a significant increase in neutrophil influx until 18 h postinstillation. The increase in neutrophils induced by UFNi at this timepoint was comparable to that induced by UFCo and UFCB. UFTi did not induce a significant increase in neutrophils following instillation into the rat lung. The levels of MIP-2 observed at 4 h and neutrophil influx at 18 h induced by the particle samples were consistent with the pattern of surface free radical generation (as measured by the plasmid scission assay) whereby UFCo, UFCB, and UFNi all cause significant increases in inflammatory markers, as well as inducing a significant depletion of supercoiled plasmid DNA, indicative of hydroxyl radical generation. A role for free radicals and reactive oxygen species (ROS) in mediating ultrafine inflammation is further strengthened by the ability of the antioxidants N-acetylcysteine (NAC) and glutathione monoethyl ester (GSHme) to block the particle induced release of tumour necrosis factor-alpha (TNF-alpha) from alveolar macrophages in vitro. The ultrafine particles in PM10 may cause adverse effects via oxidative stress, and this could have implications for susceptible individuals. Susceptible individuals, such as those with COPD or asthma, already exhibit preexisting oxidative stress and hence are in a primed state for further oxidative stress induced by occupational or environmental particles.. particulate air-pollution| nf-kappa-b| oxidative stress| carbon-black| transition-metals| intratracheal instillation| surface-area| exposure| lung| glutathione.	JAN-2003	particulate air-pollution| nf-kappa-b| oxidative stress| carbon-black| transition-metals| intratracheal instillation| surface-area| exposure| lung| glutathione	Dick, CAJ; Brown, DM; Donaldson, K; Stone, V	The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types		INHALATION TOXICOLOGY		PARTICULATE AIR-POLLUTION; NF-KAPPA-B; OXIDATIVE STRESS; CARBON-BLACK; TRANSITION-METALS; INTRATRACHEAL INSTILLATION; SURFACE-AREA; EXPOSURE; LUNG; GLUTATHIONE	PM10 contains an ultrafine component, which is generally derived from combustion processes. This ultrafine fraction may be a factor in the increases in exacerbations of respiratory disease and deaths from cardiorespiratory causes associated with transient increases in levels of PM10. By using four different ultrafine particles (carbon black, cobalt, nickel, and titanium dioxide), we set out to determine the attributes of the ultrafine particle (surface area, chemical composition, particle number, or surface reactivity) that contribute most to its toxicity and proinflammatory effects both in vivo and in vitro. Instillation of 125 mug ultrafine carbon black (UFCB) and ultrafine cobalt (UFCo) particles induced a significant influx of neutrophils at both 4 and 18 h postinstillation. Accompanying the influx of neutrophils was an increase in macrophage inflammatory protein-2 (MIP-2) (at 4 h) and an increase in gamma-glutamyl transpeptidase (at 18 h) in bronchoalveolar lavage fluid (BAL). Ultrafine nickel (UFNi) did not induce a significant increase in neutrophil influx until 18 h postinstillation. The increase in neutrophils induced by UFNi at this timepoint was comparable to that induced by UFCo and UFCB. UFTi did not induce a significant increase in neutrophils following instillation into the rat lung. The levels of MIP-2 observed at 4 h and neutrophil influx at 18 h induced by the particle samples were consistent with the pattern of surface free radical generation (as measured by the plasmid scission assay) whereby UFCo, UFCB, and UFNi all cause significant increases in inflammatory markers, as well as inducing a significant depletion of supercoiled plasmid DNA, indicative of hydroxyl radical generation. A role for free radicals and reactive oxygen species (ROS) in mediating ultrafine inflammation is further strengthened by the ability of the antioxidants N-acetylcysteine (NAC) and glutathione monoethyl ester (GSHme) to block the particle induced release of tumour necrosis factor-alpha (TNF-alpha) from alveolar macrophages in vitro. The ultrafine particles in PM10 may cause adverse effects via oxidative stress, and this could have implications for susceptible individuals. Susceptible individuals, such as those with COPD or asthma, already exhibit preexisting oxidative stress and hence are in a primed state for further oxidative stress induced by occupational or environmental particles.	38	223	2003	14	10.1080/08958370304454	Toxicology
Inhaler mishandling remains common in real life and is associated with reduced disease control. Proper inhaler technique is crucial for effective management of asthma and COPD. This multi-centre, cross-sectional, observational study investigates the prevalence of inhaler mishandling in a large population of experienced patients referring to chest clinics; to analyze the variables associated with misuse and the relationship between inhaler handling and health-care resources use and disease control. We enrolled 1664 adult subjects (mean age 62 years) affected mostly by COPD (52%) and asthma (42%). Respectively, 843 and 1113 patients were using MDIs and DP's at home; of the latter, the users of Aerolizer (R), Diskus (R), HandiHaler (R) and Turbuhaler (R) were 82, 467, 505 and 361. We have a total of 2288 records of inhaler technique. Critical mistakes were widely distributed among users of all the inhalers, ranging from 12% for MDIs, 35% for Diskus (R) and HandiHaler (R) and 44% for Turbuhaler (R). Independently of the inhaler, we found the strongest association between inhaler misuse and older age (p = 0.008), lower schooling (p = 0.001) and lack of instruction received for inhaler technique by health caregivers (p < 0.001). Inhaler misuse was associated with increased risk of hospitalization (p = 0.001), emergency room visits (p < 0.001), courses of oral steroids (p < 0.001) and antimicrobials (p < 0.001) and poor disease control evaluated as an ACT score for the asthmatics (p < 0.0001) and the whole population (p < 0.0001). We conclude that inhaler mishandling continues to be common in experienced outpatients referring to chest clinics and associated with increased unscheduled health-care resource use and poor clinical control. Instruction by health caregivers is the only modifiable factor useful for reducing inhaler mishandling (C) 2011 Elsevier Ltd. All rights reserved.. asthma| copd| mdi| dpi| inhaler technique| patient education|metered-dose inhaler| dry powder inhalers| inhalation technique| drug-delivery| clinical consequences| lung deposition| patient| asthma| misuse| volumes.	JUN-2011	asthma| copd| mdi| dpi| inhaler technique| patient education|metered-dose inhaler| dry powder inhalers| inhalation technique| drug-delivery| clinical consequences| lung deposition| patient| asthma| misuse| volumes	Melani, AS; Bonavia, M; Cilenti, V; Cinti, C; Lodi, M; Martucci, P; Serra, M; Scichilone, N; Sestini, P; Aliani, M; Neri, M	Inhaler mishandling remains common in real life and is associated with reduced disease control		RESPIRATORY MEDICINE	Asthma; COPD; MDI; DPI; Inhaler technique; Patient education	METERED-DOSE INHALER; DRY POWDER INHALERS; INHALATION TECHNIQUE; DRUG-DELIVERY; CLINICAL CONSEQUENCES; LUNG DEPOSITION; PATIENT; ASTHMA; MISUSE; VOLUMES	Proper inhaler technique is crucial for effective management of asthma and COPD. This multi-centre, cross-sectional, observational study investigates the prevalence of inhaler mishandling in a large population of experienced patients referring to chest clinics; to analyze the variables associated with misuse and the relationship between inhaler handling and health-care resources use and disease control. We enrolled 1664 adult subjects (mean age 62 years) affected mostly by COPD (52%) and asthma (42%). Respectively, 843 and 1113 patients were using MDIs and DP's at home; of the latter, the users of Aerolizer (R), Diskus (R), HandiHaler (R) and Turbuhaler (R) were 82, 467, 505 and 361. We have a total of 2288 records of inhaler technique. Critical mistakes were widely distributed among users of all the inhalers, ranging from 12% for MDIs, 35% for Diskus (R) and HandiHaler (R) and 44% for Turbuhaler (R). Independently of the inhaler, we found the strongest association between inhaler misuse and older age (p = 0.008), lower schooling (p = 0.001) and lack of instruction received for inhaler technique by health caregivers (p < 0.001). Inhaler misuse was associated with increased risk of hospitalization (p = 0.001), emergency room visits (p < 0.001), courses of oral steroids (p < 0.001) and antimicrobials (p < 0.001) and poor disease control evaluated as an ACT score for the asthmatics (p < 0.0001) and the whole population (p < 0.0001). We conclude that inhaler mishandling continues to be common in experienced outpatients referring to chest clinics and associated with increased unscheduled health-care resource use and poor clinical control. Instruction by health caregivers is the only modifiable factor useful for reducing inhaler mishandling (C) 2011 Elsevier Ltd. All rights reserved.	31	222	2011	9	10.1016/j.rmed.2011.01.005	Cardiovascular System & Cardiology; Respiratory System
Childhood Incident Asthma and Traffic-Related Air Pollution at Home and School. BACKGROUND: Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma. OBJECTIVES: We evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools. Methods: Parent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma-and wheezing-free at study entry into the Southern California Children's Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO(2)), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric. RESULTS: Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25-1.82] and near schools (HR 1.45; 95% CI, 1.06-1.98). Ambient NO(2) measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18-4.01). In models with both NO(2) and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO(2) was attenuated (HR 1.37; 95% CI, 0.69-2.71). CONCLUSIONS: Traffic-related pollution exposure at school and homes may both contribute to the development of asthma.. air pollution| asthma| child| epidemiology| vehicular traffic|childrens respiratory health| nitrogen-dioxide| allergic sensitization| ultrafine particles| size distribution| public-schools| major highway| los-angeles| busy roads| exposure.	JUL-2010	air pollution| asthma| child| epidemiology| vehicular traffic|childrens respiratory health| nitrogen-dioxide| allergic sensitization| ultrafine particles| size distribution| public-schools| major highway| los-angeles| busy roads| exposure	McConnell, R; Islam, T; Shankardass, K; Jerrett, M; Lurmann, F; Gilliland, F; Gauderman, J; Avol, E; Kunzli, N; Yao, L; Peters, J; Berhane, K	Childhood Incident Asthma and Traffic-Related Air Pollution at Home and School		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma; child; epidemiology; vehicular traffic	CHILDRENS RESPIRATORY HEALTH; NITROGEN-DIOXIDE; ALLERGIC SENSITIZATION; ULTRAFINE PARTICLES; SIZE DISTRIBUTION; PUBLIC-SCHOOLS; MAJOR HIGHWAY; LOS-ANGELES; BUSY ROADS; EXPOSURE	BACKGROUND: Traffic-related air pollution has been associated with adverse cardiorespiratory effects, including increased asthma prevalence. However, there has been little study of effects of traffic exposure at school on new-onset asthma. OBJECTIVES: We evaluated the relationship of new-onset asthma with traffic-related pollution near homes and schools. Methods: Parent-reported physician diagnosis of new-onset asthma (n = 120) was identified during 3 years of follow-up of a cohort of 2,497 kindergarten and first-grade children who were asthma-and wheezing-free at study entry into the Southern California Children's Health Study. We assessed traffic-related pollution exposure based on a line source dispersion model of traffic volume, distance from home and school, and local meteorology. Regional ambient ozone, nitrogen dioxide (NO(2)), and particulate matter were measured continuously at one central site monitor in each of 13 study communities. Hazard ratios (HRs) for new-onset asthma were scaled to the range of ambient central site pollutants and to the residential interquartile range for each traffic exposure metric. RESULTS: Asthma risk increased with modeled traffic-related pollution exposure from roadways near homes [HR 1.51; 95% confidence interval (CI), 1.25-1.82] and near schools (HR 1.45; 95% CI, 1.06-1.98). Ambient NO(2) measured at a central site in each community was also associated with increased risk (HR 2.18; 95% CI, 1.18-4.01). In models with both NO(2) and modeled traffic exposures, there were independent associations of asthma with traffic-related pollution at school and home, whereas the estimate for NO(2) was attenuated (HR 1.37; 95% CI, 0.69-2.71). CONCLUSIONS: Traffic-related pollution exposure at school and homes may both contribute to the development of asthma.	50	221	2010	6	10.1289/ehp.0901232	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Structure and function of immunoglobulins. Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2. (J Allergy Clin Immunol 2010;125:S41-52.). antibody structure| antibody function| immunoglobulin structure| immunoglobulin function| immunoglobulin gene rearrangement| class switching| somatic hypermutation|monoclonal-antibody| somatic hypermutation| igg1 antibodies| binding| locus| glycosylation| diversity| sequence| region| genes.	FEB-2010	antibody structure| antibody function| immunoglobulin structure| immunoglobulin function| immunoglobulin gene rearrangement| class switching| somatic hypermutation|monoclonal-antibody| somatic hypermutation| igg1 antibodies| binding| locus| glycosylation| diversity| sequence| region| genes	Schroeder, HW; Cavacini, L	Structure and function of immunoglobulins		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Antibody structure; antibody function; immunoglobulin structure; immunoglobulin function; immunoglobulin gene rearrangement; class switching; somatic hypermutation	MONOCLONAL-ANTIBODY; SOMATIC HYPERMUTATION; IGG1 ANTIBODIES; BINDING; LOCUS; GLYCOSYLATION; DIVERSITY; SEQUENCE; REGION; GENES	Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2. (J Allergy Clin Immunol 2010;125:S41-52.)	52	221	2010	12	10.1016/j.jaci.2009.09.046	Allergy; Immunology
Traffic-related air pollution near busy roads - The East Bay children's respiratory health study. Recent studies, primarily in Europe, have reported associations between respiratory symptoms and residential proximity to traffic; however, few have measured traffic pollutants or provided information about local air quality. We conducted a school-based, cross-sectional study in the San Francisco Bay Area in 2001. Information on current bronchitis symptoms and asthma, home environment, and demographics was obtained by parental questionnaire (n = 1,109). Concentrations of traffic pollutants (particulate matter, black carbon, total nitrogen oxides [NOX], and nitrogen dioxide [NO2]) were measured at 10 school sites during several seasons. Although pollutant concentrations were relatively low, we observed differences in concentrations between schools nearby versus those more distant (or upwind) from major roads. Using a two-stage multiple-logistic regression model, we found associations between respiratory symptoms and traffic-related pollutants. Among,those living at their current residence for at least 1 year, the adjusted odds ratio for asthma in relationship to an interquartile difference in NOX was 1.07 (95% confidence interval, 1.00-1.14). Thus, we found spatial variability in traffic pollutants and associated differences in respiratory symptoms in a region with good air quality. Our findings support the hypothesis that traffic-related pollution is associated with respiratory symptoms in children.. air pollution| asthma| bronchitis| epidemiology| vehicle emissions|southern california communities| childhood asthma| allergic sensitization| carbon concentration| differing levels| lung-function| symptoms| exposure| particles| ambient.	SEP 1-2004	air pollution| asthma| bronchitis| epidemiology| vehicle emissions|southern california communities| childhood asthma| allergic sensitization| carbon concentration| differing levels| lung-function| symptoms| exposure| particles| ambient	Kim, JJ; Smorodinsky, S; Lipsett, M; Singer, BC; Hodgson, AT; Ostro, B	Traffic-related air pollution near busy roads - The East Bay children's respiratory health study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	air pollution; asthma; bronchitis; epidemiology; vehicle emissions	SOUTHERN CALIFORNIA COMMUNITIES; CHILDHOOD ASTHMA; ALLERGIC SENSITIZATION; CARBON CONCENTRATION; DIFFERING LEVELS; LUNG-FUNCTION; SYMPTOMS; EXPOSURE; PARTICLES; AMBIENT	Recent studies, primarily in Europe, have reported associations between respiratory symptoms and residential proximity to traffic; however, few have measured traffic pollutants or provided information about local air quality. We conducted a school-based, cross-sectional study in the San Francisco Bay Area in 2001. Information on current bronchitis symptoms and asthma, home environment, and demographics was obtained by parental questionnaire (n = 1,109). Concentrations of traffic pollutants (particulate matter, black carbon, total nitrogen oxides [NOX], and nitrogen dioxide [NO2]) were measured at 10 school sites during several seasons. Although pollutant concentrations were relatively low, we observed differences in concentrations between schools nearby versus those more distant (or upwind) from major roads. Using a two-stage multiple-logistic regression model, we found associations between respiratory symptoms and traffic-related pollutants. Among,those living at their current residence for at least 1 year, the adjusted odds ratio for asthma in relationship to an interquartile difference in NOX was 1.07 (95% confidence interval, 1.00-1.14). Thus, we found spatial variability in traffic pollutants and associated differences in respiratory symptoms in a region with good air quality. Our findings support the hypothesis that traffic-related pollution is associated with respiratory symptoms in children.	38	221	2004	7	10.1164/rccm.200403-2810C	General & Internal Medicine; Respiratory System
Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study. Background Particulate pollution is associated with the occurrence of asthma and allergy. The model pollutant, diesel exhaust particles, can participate with allergens in starting and exacerbating allergic airway diseases in part by production of reactive oxygen species. Glutathione-S-transferases (GSTs) can metabolise reactive oxygen species and detoxify xenobiotics present in diesel exhaust particles. We tested the hypothesis that null genotypes for GSTM1 and GSTT1, and GSTP1 codon 105 variants (I105 and V105) are key regulators of the adjuvant effects of diesel exhaust particles on allergic responses. Methods Patients sensitive to the ragweed allergen were challenged intranasally with allergen alone and with allergen plus diesel exhaust particles in a randomised order at separate visits. Nasal allergen-specific IgE, histamine, interleukin 4, and interferon gamma concentrations were measured before and 24 h after challenge. Findings Individuals with GSTM1 null or the GSTP1 I105 wildtype genotypes showed enhanced nasal allergic responses in the presence of diesel exhaust particles. Compared with patients with a functional GSTM1 genotype, GSTM1 null patients had a significantly larger increase in IgE (median 102.5 U/mL [range 1.0-510.5] vs 45.5 U/mL [1.5-60.6], p=0.03) and histamine (14.0 nmol/L [-0.2-24.7] vs 7.4 nmol/L [1.2-12.3], p=0.02) after diesel exhaust particles plus allergen challenge. The I105 GSTP1 genotype was associated with an increase in IgE (120.3 U/mL [6.7-510.5] vs 27.7 U/mL [-1.5-60.6], p=0.03) and histamine (13.8 nmol/L [3.1-24.7] vs 5.2 nmol/L [-0.2-19.6], p=0.01) after challenge with diesel exhaust particles and allergens. The diesel exhaust particles enhancement was largest in patients with both the GSTM1 null and GSTP1 I/I genotypes. Interpretation GSTM1 and GSTP1 modify the adjuvant effect of diesel exhaust particles on allergic inflammation.. diesel exhaust particles| air-pollution| in-vivo| nasal challenge| cytokine production| tobacco-smoke| lung-cancer| asthma| exposure| children.	JAN 10-2004	diesel exhaust particles| air-pollution| in-vivo| nasal challenge| cytokine production| tobacco-smoke| lung-cancer| asthma| exposure| children	Gilliland, FD; Li, YF; Saxon, A; Diaz-Sanchez, D	Effect of glutathione-S-transferase M1 and P1 genotypes on xenobiotic enhancement of allergic responses: randomised, placebo-controlled crossover study		LANCET		DIESEL EXHAUST PARTICLES; AIR-POLLUTION; IN-VIVO; NASAL CHALLENGE; CYTOKINE PRODUCTION; TOBACCO-SMOKE; LUNG-CANCER; ASTHMA; EXPOSURE; CHILDREN	Background Particulate pollution is associated with the occurrence of asthma and allergy. The model pollutant, diesel exhaust particles, can participate with allergens in starting and exacerbating allergic airway diseases in part by production of reactive oxygen species. Glutathione-S-transferases (GSTs) can metabolise reactive oxygen species and detoxify xenobiotics present in diesel exhaust particles. We tested the hypothesis that null genotypes for GSTM1 and GSTT1, and GSTP1 codon 105 variants (I105 and V105) are key regulators of the adjuvant effects of diesel exhaust particles on allergic responses. Methods Patients sensitive to the ragweed allergen were challenged intranasally with allergen alone and with allergen plus diesel exhaust particles in a randomised order at separate visits. Nasal allergen-specific IgE, histamine, interleukin 4, and interferon gamma concentrations were measured before and 24 h after challenge. Findings Individuals with GSTM1 null or the GSTP1 I105 wildtype genotypes showed enhanced nasal allergic responses in the presence of diesel exhaust particles. Compared with patients with a functional GSTM1 genotype, GSTM1 null patients had a significantly larger increase in IgE (median 102.5 U/mL [range 1.0-510.5] vs 45.5 U/mL [1.5-60.6], p=0.03) and histamine (14.0 nmol/L [-0.2-24.7] vs 7.4 nmol/L [1.2-12.3], p=0.02) after diesel exhaust particles plus allergen challenge. The I105 GSTP1 genotype was associated with an increase in IgE (120.3 U/mL [6.7-510.5] vs 27.7 U/mL [-1.5-60.6], p=0.03) and histamine (13.8 nmol/L [3.1-24.7] vs 5.2 nmol/L [-0.2-19.6], p=0.01) after challenge with diesel exhaust particles and allergens. The diesel exhaust particles enhancement was largest in patients with both the GSTM1 null and GSTP1 I/I genotypes. Interpretation GSTM1 and GSTP1 modify the adjuvant effect of diesel exhaust particles on allergic inflammation.	44	220	2004	7	10.1016/S0140-6736(03)15262-2	General & Internal Medicine
Environmental pollutants and disease in American children: Estimates of morbidity, mortality, and costs for lead poisoning, asthma, cancer, and developmental disabilities. In this study, we aimed to estimate the contribution of environmental pollutants to the incidence, prevalence, mortality, and costs of pediatric disease in American children. We examined four categories of illness: lead poisoning, asthma, cancer, and neurobehavioral disorders. To estimate the proportion of each attributable to toxins in the environment, we used an environmentally attributable fraction (EAF) model. EAFs for lead poisoning, asthma, and cancer were developed by panels of experts through a Delphi process, whereas that for neurobehavioral disorders was based on data from the National Academy of Sciences. We define environmental pollutants as toxic chemicals of human origin in air, food, water, and communities. To develop estimates of costs, we relied on data from the U.S. Environmental Protection Agency, Centers for Disease Control and Prevention, National Center for Health Statistics, the Bureau of Labor Statistics, the Health Care Financing Agency, and the Practice Management Information Corporation. EAFs were judged to be 100% for lead poisoning, 30% for asthma (range, 10-35%), 5% for cancer (range, 2-10%), and 10% for neurobehavioral disorders (range, 5-20%). Total annual costs are estimated to be $54.9 billion (range $48.8-64.8 billion): $43.4 billion for lead poisoning, $2.0 billion for asthma, $0.3 billion for childhood cancer, and $9.2 billion for neurobehavioral disorders. This sum amounts to 2.8 percent of total U.S. health care costs. This estimate is likely low because it considers only four categories of illness, incorporates conservative assumptions, ignores costs of pain and Suffering, and does not include late complications for which etiologic associations are poorly quantified. The costs of pediatric environmental disease are high, in contrast with the limited resources directed to research, tracking, and prevention.. asthma| cancer| developmental disabilities| environmental pediatrics| health economics| lead poisoning|united-states| occupational injury| childhood cancers| air-pollution| health| trends| exposure| benefits| illness| risk.	JUL-2002	asthma| cancer| developmental disabilities| environmental pediatrics| health economics| lead poisoning|united-states| occupational injury| childhood cancers| air-pollution| health| trends| exposure| benefits| illness| risk	Landrigan, PJ; Schechter, CB; Lipton, JM; Fahs, MC; Schwartz, J	Environmental pollutants and disease in American children: Estimates of morbidity, mortality, and costs for lead poisoning, asthma, cancer, and developmental disabilities		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; cancer; developmental disabilities; environmental pediatrics; health economics; lead poisoning	UNITED-STATES; OCCUPATIONAL INJURY; CHILDHOOD CANCERS; AIR-POLLUTION; HEALTH; TRENDS; EXPOSURE; BENEFITS; ILLNESS; RISK	In this study, we aimed to estimate the contribution of environmental pollutants to the incidence, prevalence, mortality, and costs of pediatric disease in American children. We examined four categories of illness: lead poisoning, asthma, cancer, and neurobehavioral disorders. To estimate the proportion of each attributable to toxins in the environment, we used an environmentally attributable fraction (EAF) model. EAFs for lead poisoning, asthma, and cancer were developed by panels of experts through a Delphi process, whereas that for neurobehavioral disorders was based on data from the National Academy of Sciences. We define environmental pollutants as toxic chemicals of human origin in air, food, water, and communities. To develop estimates of costs, we relied on data from the U.S. Environmental Protection Agency, Centers for Disease Control and Prevention, National Center for Health Statistics, the Bureau of Labor Statistics, the Health Care Financing Agency, and the Practice Management Information Corporation. EAFs were judged to be 100% for lead poisoning, 30% for asthma (range, 10-35%), 5% for cancer (range, 2-10%), and 10% for neurobehavioral disorders (range, 5-20%). Total annual costs are estimated to be $54.9 billion (range $48.8-64.8 billion): $43.4 billion for lead poisoning, $2.0 billion for asthma, $0.3 billion for childhood cancer, and $9.2 billion for neurobehavioral disorders. This sum amounts to 2.8 percent of total U.S. health care costs. This estimate is likely low because it considers only four categories of illness, incorporates conservative assumptions, ignores costs of pain and Suffering, and does not include late complications for which etiologic associations are poorly quantified. The costs of pediatric environmental disease are high, in contrast with the limited resources directed to research, tracking, and prevention.	90	220	2002	8		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Sensitization to common allergens and its association with allergic disorders at age 4 years: A whole population birth cohort study. Background. Atopy is defined as the genetic propensity to develop immunoglobulin E antibodies in response to exposure to allergens and assessed by skin prick test responses to common allergens. Although it is generally agreed that atopy is an important risk factor for allergic diseases such as asthma, rhinitis, and eczema, the extent to which atopy accounts for these diseases is controversial. Objective. We aim to describe the prevalence of sensitization to common allergens and investigate the degree of association of atopy (as defined by positive skin prick test to 1 or more common allergens) to asthma, rhinitis, and eczema in a birth cohort at the age of 4 years. Methods. A birth cohort of 1456 children was recruited over a 14-month period (1989-1990). These children have been seen previously at 1 and 2 years of age. At 4 years, 1218 children were reviewed and an interview was administered or postal questionnaire was completed for the presence of allergic diseases (asthma, rhinitis, and eczema). Additionally, in 981 children, skin prick tests with a battery of 12 common allergens were performed. Allergens were house dust mite (Dermatophagoides pteronyssimus), grass pollen mix, cat, dog, Alternaria alternata, Cladosporium herbarum, cow's milk, hen's egg, soya, cod, wheat, and peanut. A mean wheal diameter of at least 3 mm greater than the negative control was taken as positive. This analysis is confined to the 981 (67% of the original population) who also had skin prick tests to the standard battery. chi (2) tests were used to test the univariate association between each allergic disease and positive skin test. Multiple logistic regression analysis was performed to obtain the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the independent effect of sensitization to each allergen on allergic disease, adjusting for the effect of sensitization to other allergens. To ascertain how much of allergic disease is attributable to atopy, we estimated the population-attributable risk. This was calculated with the formula: P(R - 1) where R is the OR for the allergic disease under consideration and P is the proportion of atopy in children with that disease. Results. Children who were skin prick-tested at 4 years were similar in most characteristics to the rest of the population, except that they had a higher prevalence of allergic disease. Allergic disorders (asthma, rhinitis, and eczema) were present in 276 (28.1%) of 981. One hundred ninety-two (19.6%) children were atopic (positive reaction to 1 or more allergens). Sensitization to inhalant allergens was relatively common (19.2%) as compared with food allergens (3.5%). House dust mite (11.9%), grass pollen (7.8%), and cat (5.8%) were the most common positive reactions. A test to the 4 most common allergens (house dust mite, grass pollen, cat, and A alternata) could detect 94% of the atopic children. Sensitization to the 4 most common allergens was strongly associated with the presence of allergic disorders. There was a graded effect with the potent allergens, such as house dust mite, having the greatest impact. For example, 50% of children sensitized to house dust mite had asthma as opposed to 44% sensitized to cat, 42% sensitized to grass pollen, and 32% sensitized to A alternata. Overall, 68.4% of children sensitized to house dust mite had asthma, eczema, and/or rhinitis. The respective figures for grass pollen, cat, and A alternata were 64.9%, 66.7%, and 57.4%. The proportion of children sensitized to cat was not higher in households with cat ownership (households with cats: 5.1% [19/374]; households without cats: 6.2% [36/580]; not significant [NS]). Similarly, no difference was seen in sensitization to dog in households with and without dogs (households with dogs: 1.8% [5/282]; households without dogs: 2.8% [19/673]; NS). Boys were atopic more often than girls at this age (male: 112 of 497 [22.5%] vs female: 80 of 484 [16.5%]; OR: 1.47, 95% CI: 1.07-2.02). Male preponderance was observed with most allergens, but this was statistically significant only for house dust mite (male: 75/497 [15.1%] vs female: 42/484 [8.7%]; OR: 1.87; CI: 1.25-2.79) and grass pollen (male: 51/497 [10.3%] vs female: 26/484 [5.4%]; OR: 2.01; CI: 1.23-3.29). An independent effect of allergen sensitization on asthma was observed only with house dust mite with an OR of 8.07 (CI: 4.60-14.14). The highest independent risk for rhinitis was sensitization to grass pollen (OR: 5.02; CI: 2.21-11.41), and for eczema, sensitization to peanut (OR: 4.65; CI: 1.02-21.34). The majority of children (98/192) were sensitized to >1 allergen. A graded effect was observed with the risk of allergic disease in the child increasing with the number of positive skin prick test reactions. This effect was consistent throughout the spectrum of allergic diseases (asthma, eczema, and rhinitis). Nearly 80% of the children with positive skin test reactions to 4 or more allergens had asthma, eczema, and/or rhinitis compared with 20%, if they were nonatopic. The prevalence of atopy in asthmatic children was 44%. With an OR of 4.56, the population-attributable risk was calculated to be 35%. Fifty-five percent of children with rhinitis were atopic, and the OR of rhinitis was 5.85. Therefore, 46% of the cases of rhinitis could be attributable to atopy. The population-attributable risk of atopy for eczema was 32% (the prevalence of atopy in children with eczema: 43%; and the OR for the development of eczema: 3.86). Conclusion. Atopy is closely associated with asthma, rhinitis, and eczema at 4 years of age, with a direct and linear relationship. However, the proportion of cases of allergic disease attributable to atopy is <50%. We propose a model for the development of allergic disorders, where 30% to 40% of cases of allergic disease (asthma, eczema, and rhinitis) in early childhood are attributable to atopy and 60% to 70% of cases could be accounted for by organ-based and other factors.. atopy| allergic diseases| asthma| eczema| rhinitis| skin-prick test|skin-test reactivity| house-dust mite| childhood asthma| serum ige| airway responsiveness| environmental-factors| inhalant allergens| risk-factors| hay-fever| atopy.	AUG-2001	atopy| allergic diseases| asthma| eczema| rhinitis| skin-prick test|skin-test reactivity| house-dust mite| childhood asthma| serum ige| airway responsiveness| environmental-factors| inhalant allergens| risk-factors| hay-fever| atopy	Arshad, SH; Tariq, SM; Matthews, S; Hakim, E	Sensitization to common allergens and its association with allergic disorders at age 4 years: A whole population birth cohort study		PEDIATRICS	atopy; allergic diseases; asthma; eczema; rhinitis; skin-prick test	SKIN-TEST REACTIVITY; HOUSE-DUST MITE; CHILDHOOD ASTHMA; SERUM IGE; AIRWAY RESPONSIVENESS; ENVIRONMENTAL-FACTORS; INHALANT ALLERGENS; RISK-FACTORS; HAY-FEVER; ATOPY	Background. Atopy is defined as the genetic propensity to develop immunoglobulin E antibodies in response to exposure to allergens and assessed by skin prick test responses to common allergens. Although it is generally agreed that atopy is an important risk factor for allergic diseases such as asthma, rhinitis, and eczema, the extent to which atopy accounts for these diseases is controversial. Objective. We aim to describe the prevalence of sensitization to common allergens and investigate the degree of association of atopy (as defined by positive skin prick test to 1 or more common allergens) to asthma, rhinitis, and eczema in a birth cohort at the age of 4 years. Methods. A birth cohort of 1456 children was recruited over a 14-month period (1989-1990). These children have been seen previously at 1 and 2 years of age. At 4 years, 1218 children were reviewed and an interview was administered or postal questionnaire was completed for the presence of allergic diseases (asthma, rhinitis, and eczema). Additionally, in 981 children, skin prick tests with a battery of 12 common allergens were performed. Allergens were house dust mite (Dermatophagoides pteronyssimus), grass pollen mix, cat, dog, Alternaria alternata, Cladosporium herbarum, cow's milk, hen's egg, soya, cod, wheat, and peanut. A mean wheal diameter of at least 3 mm greater than the negative control was taken as positive. This analysis is confined to the 981 (67% of the original population) who also had skin prick tests to the standard battery. chi (2) tests were used to test the univariate association between each allergic disease and positive skin test. Multiple logistic regression analysis was performed to obtain the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the independent effect of sensitization to each allergen on allergic disease, adjusting for the effect of sensitization to other allergens. To ascertain how much of allergic disease is attributable to atopy, we estimated the population-attributable risk. This was calculated with the formula: P(R - 1) where R is the OR for the allergic disease under consideration and P is the proportion of atopy in children with that disease. Results. Children who were skin prick-tested at 4 years were similar in most characteristics to the rest of the population, except that they had a higher prevalence of allergic disease. Allergic disorders (asthma, rhinitis, and eczema) were present in 276 (28.1%) of 981. One hundred ninety-two (19.6%) children were atopic (positive reaction to 1 or more allergens). Sensitization to inhalant allergens was relatively common (19.2%) as compared with food allergens (3.5%). House dust mite (11.9%), grass pollen (7.8%), and cat (5.8%) were the most common positive reactions. A test to the 4 most common allergens (house dust mite, grass pollen, cat, and A alternata) could detect 94% of the atopic children. Sensitization to the 4 most common allergens was strongly associated with the presence of allergic disorders. There was a graded effect with the potent allergens, such as house dust mite, having the greatest impact. For example, 50% of children sensitized to house dust mite had asthma as opposed to 44% sensitized to cat, 42% sensitized to grass pollen, and 32% sensitized to A alternata. Overall, 68.4% of children sensitized to house dust mite had asthma, eczema, and/or rhinitis. The respective figures for grass pollen, cat, and A alternata were 64.9%, 66.7%, and 57.4%. The proportion of children sensitized to cat was not higher in households with cat ownership (households with cats: 5.1% [19/374]; households without cats: 6.2% [36/580]; not significant [NS]). Similarly, no difference was seen in sensitization to dog in households with and without dogs (households with dogs: 1.8% [5/282]; households without dogs: 2.8% [19/673]; NS). Boys were atopic more often than girls at this age (male: 112 of 497 [22.5%] vs female: 80 of 484 [16.5%]; OR: 1.47, 95% CI: 1.07-2.02). Male preponderance was observed with most allergens, but this was statistically significant only for house dust mite (male: 75/497 [15.1%] vs female: 42/484 [8.7%]; OR: 1.87; CI: 1.25-2.79) and grass pollen (male: 51/497 [10.3%] vs female: 26/484 [5.4%]; OR: 2.01; CI: 1.23-3.29). An independent effect of allergen sensitization on asthma was observed only with house dust mite with an OR of 8.07 (CI: 4.60-14.14). The highest independent risk for rhinitis was sensitization to grass pollen (OR: 5.02; CI: 2.21-11.41), and for eczema, sensitization to peanut (OR: 4.65; CI: 1.02-21.34). The majority of children (98/192) were sensitized to >1 allergen. A graded effect was observed with the risk of allergic disease in the child increasing with the number of positive skin prick test reactions. This effect was consistent throughout the spectrum of allergic diseases (asthma, eczema, and rhinitis). Nearly 80% of the children with positive skin test reactions to 4 or more allergens had asthma, eczema, and/or rhinitis compared with 20%, if they were nonatopic. The prevalence of atopy in asthmatic children was 44%. With an OR of 4.56, the population-attributable risk was calculated to be 35%. Fifty-five percent of children with rhinitis were atopic, and the OR of rhinitis was 5.85. Therefore, 46% of the cases of rhinitis could be attributable to atopy. The population-attributable risk of atopy for eczema was 32% (the prevalence of atopy in children with eczema: 43%; and the OR for the development of eczema: 3.86). Conclusion. Atopy is closely associated with asthma, rhinitis, and eczema at 4 years of age, with a direct and linear relationship. However, the proportion of cases of allergic disease attributable to atopy is <50%. We propose a model for the development of allergic disorders, where 30% to 40% of cases of allergic disease (asthma, eczema, and rhinitis) in early childhood are attributable to atopy and 60% to 70% of cases could be accounted for by organ-based and other factors.	34	220	2001	8	10.1542/peds.108.2.e33	Pediatrics
Exposure assessment of air pollutants: a review on spatial heterogeneity and indoor/outdoor/personal exposure to suspended particulate matter, nitrogen dioxide and ozone. This review describes databases of small-scale spatial variations and indoor, outdoor and personal measurements of air pollutants with the main focus on suspended particulate matter, and to a lesser extent, nitrogen dioxide and photochemical pollutants. The basic definitions and concepts of an exposure measurement are introduced as well as some study design considerations and implications of imprecise exposure measurements. Suspended particulate matter is complex with respect to particle size distributions, the chemical composition and its sources. With respect to small-scale spatial variations in urban areas, largest variations occur in the ultrafine (<0.1 <mu>m) and the coarse mode (PM10-2.5, resuspended dust). Secondary aerosols which contribute to the accumulation mode (0.1-2 mum) show quite homogenous spatial distribution. In general, small-scale spatial variations of PM2.5 were described to be smaller than the spatial variations of PM10. Recent studies in outdoor air show that ultrafine particle number counts have large spatial variations and that they are not well correlated to mass data. Sources of indoor particles are from outdoors and some specific indoor sources such as smoking and cooking for fine particles or moving of people (resuspension of dust) for coarse particles. The relationships between indoor, outdoor and personal levels are complex. The finer the particle size, the better becomes the correlation between indoor, outdoor and personal levels. Furthermore, correlations between these parameters are better in longitudinal analyses than in cross-sectional analyses. For NO2 and O-3 the air chemistry is important. Both have considerable small-scale spatial variations within urban areas. In the absence of indoor sources such as gas appliances, NO2 indoor/outdoor relationships are strong. For ozone, indoor levels are quite small. The study hypothesis largely determines the choice of a specific concept in exposure assessment, i.e. whether personal sampling is needed or if ambient monitoring is sufficient. Careful evaluation of the validity and improvements in precision of an exposure measure reduce error in the measurements and bias in the exposure-effect relationship. (C) 2000 Published by Elsevier Science Ltd.. exposure assessment| particles| pm10| pm2.5| no2| o-3| bioaerosols|volatile organic-compounds| residential no2 characterization| southern california community| grass-pollen allergen| personal exposure| airborne particles| environmental epidemiology| biological markers| pulmonary-function| mass concentration.	2001	exposure assessment| particles| pm10| pm2.5| no2| o-3| bioaerosols|volatile organic-compounds| residential no2 characterization| southern california community| grass-pollen allergen| personal exposure| airborne particles| environmental epidemiology| biological markers| pulmonary-function| mass concentration	Monn, C	Exposure assessment of air pollutants: a review on spatial heterogeneity and indoor/outdoor/personal exposure to suspended particulate matter, nitrogen dioxide and ozone		ATMOSPHERIC ENVIRONMENT	exposure assessment; particles; PM10; PM2.5; NO2; O-3; bioaerosols	VOLATILE ORGANIC-COMPOUNDS; RESIDENTIAL NO2 CHARACTERIZATION; SOUTHERN CALIFORNIA COMMUNITY; GRASS-POLLEN ALLERGEN; PERSONAL EXPOSURE; AIRBORNE PARTICLES; ENVIRONMENTAL EPIDEMIOLOGY; BIOLOGICAL MARKERS; PULMONARY-FUNCTION; MASS CONCENTRATION	This review describes databases of small-scale spatial variations and indoor, outdoor and personal measurements of air pollutants with the main focus on suspended particulate matter, and to a lesser extent, nitrogen dioxide and photochemical pollutants. The basic definitions and concepts of an exposure measurement are introduced as well as some study design considerations and implications of imprecise exposure measurements. Suspended particulate matter is complex with respect to particle size distributions, the chemical composition and its sources. With respect to small-scale spatial variations in urban areas, largest variations occur in the ultrafine (<0.1 <mu>m) and the coarse mode (PM10-2.5, resuspended dust). Secondary aerosols which contribute to the accumulation mode (0.1-2 mum) show quite homogenous spatial distribution. In general, small-scale spatial variations of PM2.5 were described to be smaller than the spatial variations of PM10. Recent studies in outdoor air show that ultrafine particle number counts have large spatial variations and that they are not well correlated to mass data. Sources of indoor particles are from outdoors and some specific indoor sources such as smoking and cooking for fine particles or moving of people (resuspension of dust) for coarse particles. The relationships between indoor, outdoor and personal levels are complex. The finer the particle size, the better becomes the correlation between indoor, outdoor and personal levels. Furthermore, correlations between these parameters are better in longitudinal analyses than in cross-sectional analyses. For NO2 and O-3 the air chemistry is important. Both have considerable small-scale spatial variations within urban areas. In the absence of indoor sources such as gas appliances, NO2 indoor/outdoor relationships are strong. For ozone, indoor levels are quite small. The study hypothesis largely determines the choice of a specific concept in exposure assessment, i.e. whether personal sampling is needed or if ambient monitoring is sufficient. Careful evaluation of the validity and improvements in precision of an exposure measure reduce error in the measurements and bias in the exposure-effect relationship. (C) 2000 Published by Elsevier Science Ltd.	219	220	2001	32	10.1016/S1352-2310(00)00330-7	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Farm living: effects on childhood asthma and allergy. Numerous epidemiological studies have shown that children who grow up on traditional farms are protected from asthma, hay fever and allergic sensitization. Early-life contact with livestock and their fodder, and consumption of unprocessed cow's milk have been identified as the most effective protective exposures. Studies of the immunobiology of farm living point to activation and modulation of innate and adaptive immune responses by intense microbial exposures and possibly xenogeneic signals delivered before or soon after birth.. normal human monocytes| ifn-gamma production| school-age-children| hay-fever| early-life| birth-cohort| atopic sensitization| inverse association| microbial exposure| dendritic cells.	DEC-2010	normal human monocytes| ifn-gamma production| school-age-children| hay-fever| early-life| birth-cohort| atopic sensitization| inverse association| microbial exposure| dendritic cells	von Mutius, E; Vercelli, D	Farm living: effects on childhood asthma and allergy		NATURE REVIEWS IMMUNOLOGY		NORMAL HUMAN MONOCYTES; IFN-GAMMA PRODUCTION; SCHOOL-AGE-CHILDREN; HAY-FEVER; EARLY-LIFE; BIRTH-COHORT; ATOPIC SENSITIZATION; INVERSE ASSOCIATION; MICROBIAL EXPOSURE; DENDRITIC CELLS	Numerous epidemiological studies have shown that children who grow up on traditional farms are protected from asthma, hay fever and allergic sensitization. Early-life contact with livestock and their fodder, and consumption of unprocessed cow's milk have been identified as the most effective protective exposures. Studies of the immunobiology of farm living point to activation and modulation of innate and adaptive immune responses by intense microbial exposures and possibly xenogeneic signals delivered before or soon after birth.	80	219	2010	8	10.1038/nri2871	Immunology
Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966-2001) on the mode of early feeding in infancy and its impact on later atopic manifestations. Background: Strategies to prevent children from developing allergy have been elaborated on the basis of state-of-the-art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published previously. Here, the objective is to review the scientific literature regarding the impact of early feeding (breast milk and/or cow's milk and/or formula) on development of atopic disease. The work was performed by a multidisciplinary group of Scandinavian researchers. Methods: The search in the literature identified 4323 articles that contained at least one of the exposure and health effect terms. A total of 4191 articles were excluded mainly because they did not contain information on both exposure and health effects. Consequently, 132 studies have been scrutinized by this review group. Results: Of the 132 studies selected, 56 were regarded as conclusive. Several factors contributed to the exclusions. The studies considered conclusive by the review group were categorized according to population and study design. Conclusions: The review group concluded that breastfeeding seems to protect from the development of atopic disease. The effect appears even stronger in children with atopic heredity. If breast milk is unavailable or insufficient, extensively hydrolysed formulas are preferable to unhydrolysed or partially hydrolysed formulas in terms of the risk of some atopic manifestations.. allergy| asthma| atopic disease| breast feeding| cow's milk formula| wheezing|cows milk allergy| high-risk infants| respiratory-tract infections| partial whey hydrolysate| prospective follow-up| family history| pathogenetic role| parental smoking| childhood asthma| maternal smoking.	SEP-2003	allergy| asthma| atopic disease| breast feeding| cow's milk formula| wheezing|cows milk allergy| high-risk infants| respiratory-tract infections| partial whey hydrolysate| prospective follow-up| family history| pathogenetic role| parental smoking| childhood asthma| maternal smoking	van Odijk, J; Kull, I; Borres, MP; Brandtzaeg, P; Edberg, U; Hanson, LA; Host, A; Kuitunen, M; Olsen, SF; Skerfving, S; Sundell, J; Wille, S	Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966-2001) on the mode of early feeding in infancy and its impact on later atopic manifestations		ALLERGY	allergy; asthma; atopic disease; breast feeding; cow's milk formula; wheezing	COWS MILK ALLERGY; HIGH-RISK INFANTS; RESPIRATORY-TRACT INFECTIONS; PARTIAL WHEY HYDROLYSATE; PROSPECTIVE FOLLOW-UP; FAMILY HISTORY; PATHOGENETIC ROLE; PARENTAL SMOKING; CHILDHOOD ASTHMA; MATERNAL SMOKING	Background: Strategies to prevent children from developing allergy have been elaborated on the basis of state-of-the-art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published previously. Here, the objective is to review the scientific literature regarding the impact of early feeding (breast milk and/or cow's milk and/or formula) on development of atopic disease. The work was performed by a multidisciplinary group of Scandinavian researchers. Methods: The search in the literature identified 4323 articles that contained at least one of the exposure and health effect terms. A total of 4191 articles were excluded mainly because they did not contain information on both exposure and health effects. Consequently, 132 studies have been scrutinized by this review group. Results: Of the 132 studies selected, 56 were regarded as conclusive. Several factors contributed to the exclusions. The studies considered conclusive by the review group were categorized according to population and study design. Conclusions: The review group concluded that breastfeeding seems to protect from the development of atopic disease. The effect appears even stronger in children with atopic heredity. If breast milk is unavailable or insufficient, extensively hydrolysed formulas are preferable to unhydrolysed or partially hydrolysed formulas in terms of the risk of some atopic manifestations.	73	219	2003	11		Allergy; Immunology
Omalizumab-induced reductions in mast cell Fc epsilon RI expression and function. Background: By design, omalizumab binds free IgE in the circulation and prevents its attachment to the surface of mast cells and basophils, thereby preventing them from responding to allergens. Previously, omalizumab rapidly reduced free IgE levels, as well as basophil high-affinity IgE receptors, leading to significant reductions in basophil mediator response to allergen. It is assumed that tissue mast cells are similarly altered in their FcepsilonRI density and function. Objective: We examined the phenotypic shift of skin mast cells in parallel to that of blood basophils in 3 subjects infused with omalizumab. Methods: Three subjects with allergic rhinitis underwent intradermal skin test titration with house dust mite antigen at days 0, 7, 70, and 196 of omalizumab treatment. As control subjects, 5 untreated subjects with allergic rhinitis were evaluated at similar time points. All subjects underwent skin biopsy 18 to 24 hours later at the site of allergen injection. Biopsy specimens were characterized by means of immunohistochemisty for tryptase and FcepsilonRIalpha immunoreactivity, as well other markers (CD3, CD45RO, CD68, cutaneous lymphocyte antigen, and major basic protein). Results: Omalizumab recipients, but not control subjects, demonstrated reductions in FcepsilonRIalpha immunoreactivity at days 70 and 196 in parallel with reductions in the acute wheal response to allergen. However, no reductions in tryptase-positive cells were noted at these time points. Conclusion: Reductions in free IgE levels by omalizumab leads to a rapid reduction in basophil FcepsilonRI receptor expression. In contrast, the time course for the decrease of FcepsilonRI expression in skin mast cells is slower and associated with decreased acute allergen wheal size.. mast cells| fc epsilon ri| omalizumab| basophils|anti-ige antibody| down-regulation| in-vivo.	SEP-2004	mast cells| fc epsilon ri| omalizumab| basophils|anti-ige antibody| down-regulation| in-vivo	Beck, LA; Marcotte, GV; MacGlashan, D; Togias, A; Saini, S	Omalizumab-induced reductions in mast cell Fc epsilon RI expression and function		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	mast cells; Fc epsilon RI; omalizumab; basophils	ANTI-IGE ANTIBODY; DOWN-REGULATION; IN-VIVO	Background: By design, omalizumab binds free IgE in the circulation and prevents its attachment to the surface of mast cells and basophils, thereby preventing them from responding to allergens. Previously, omalizumab rapidly reduced free IgE levels, as well as basophil high-affinity IgE receptors, leading to significant reductions in basophil mediator response to allergen. It is assumed that tissue mast cells are similarly altered in their FcepsilonRI density and function. Objective: We examined the phenotypic shift of skin mast cells in parallel to that of blood basophils in 3 subjects infused with omalizumab. Methods: Three subjects with allergic rhinitis underwent intradermal skin test titration with house dust mite antigen at days 0, 7, 70, and 196 of omalizumab treatment. As control subjects, 5 untreated subjects with allergic rhinitis were evaluated at similar time points. All subjects underwent skin biopsy 18 to 24 hours later at the site of allergen injection. Biopsy specimens were characterized by means of immunohistochemisty for tryptase and FcepsilonRIalpha immunoreactivity, as well other markers (CD3, CD45RO, CD68, cutaneous lymphocyte antigen, and major basic protein). Results: Omalizumab recipients, but not control subjects, demonstrated reductions in FcepsilonRIalpha immunoreactivity at days 70 and 196 in parallel with reductions in the acute wheal response to allergen. However, no reductions in tryptase-positive cells were noted at these time points. Conclusion: Reductions in free IgE levels by omalizumab leads to a rapid reduction in basophil FcepsilonRI receptor expression. In contrast, the time course for the decrease of FcepsilonRI expression in skin mast cells is slower and associated with decreased acute allergen wheal size.	9	217	2004	4	10.1016/j.jaci.2004.06.032	Allergy; Immunology
To respond or not to respond: T cells in allergic asthma. The incidence of allergic asthma has almost doubled in the past two decades. Numerous epidemiological studies have linked the recent surge in atopic disease with decreased exposure to infections in early childhood as a result of a more westernized lifestyle. However, a clear mechanistic explanation for how this might occur is still lacking. An answer might lie in the presently unfolding story of various regulatory T-cell populations that can limit adaptive immune responses, including T helper 2 (T(H)2)-cell-mediated allergic airway disease.. induced airway hyperreactivity| ifn-gamma production| dendritic cells| th2 responses| murine model| cytokine production| transgenic mice| bronchial hyperresponsiveness| eosinophilic inflammation| interleukin-10 production.	MAY-2003	induced airway hyperreactivity| ifn-gamma production| dendritic cells| th2 responses| murine model| cytokine production| transgenic mice| bronchial hyperresponsiveness| eosinophilic inflammation| interleukin-10 production	Herrick, CA; Bottomly, K	To respond or not to respond: T cells in allergic asthma		NATURE REVIEWS IMMUNOLOGY		INDUCED AIRWAY HYPERREACTIVITY; IFN-GAMMA PRODUCTION; DENDRITIC CELLS; TH2 RESPONSES; MURINE MODEL; CYTOKINE PRODUCTION; TRANSGENIC MICE; BRONCHIAL HYPERRESPONSIVENESS; EOSINOPHILIC INFLAMMATION; INTERLEUKIN-10 PRODUCTION	The incidence of allergic asthma has almost doubled in the past two decades. Numerous epidemiological studies have linked the recent surge in atopic disease with decreased exposure to infections in early childhood as a result of a more westernized lifestyle. However, a clear mechanistic explanation for how this might occur is still lacking. An answer might lie in the presently unfolding story of various regulatory T-cell populations that can limit adaptive immune responses, including T helper 2 (T(H)2)-cell-mediated allergic airway disease.	116	217	2003	8	10.1038/nri1084	Immunology
A voluntary registry for peanut and tree nut allergy: Characteristics of the first 5149 registrants. Background: A voluntary registry of individuals with peanut and/or tree nut allergy was established in 1997 to learn more about these food allergies. Objective: The purpose of this study was to elucidate a variety of features of peanut and tree nut allergy among the first 5149 registry participants. Methods: The registry was established through use of a structured questionnaire distributed to all members of the Food Allergy and Anaphylaxis Network and to patients by allergists. Parental surrogates completed the forms for children under the age of 18 years. Results: Registrants were primarily children (89% of registrants were younger than 18 years of age: the median age was 5 years), reflecting the membership of the Network. Isolated peanut allergy was reported by 3482 registrants (68%), isolated tree nut allergy by 464 (9%), and allergy to both foods by 1203 (23%). Registrants were more likely to have been born in October, November, or December (odds ratio, 1.2; 95% CI, 1.18-1.23; P < .0001). The median age of reaction to peanut was 14 months, and the median age of reaction to tree nuts was 36 months; these represented the first known exposure for 74% and 68% of registrants, respectively. One half of the reactions involved more than 1 organ system, and more than 75% required treatment, frequently from medical personnel. Registrants with asthma were more likely than those without asthma to have severe reactions (33% vs 21%; P < .0001). In comparison with initial reactions, subsequent reactions due to accidental ingestion were more severe. more common outside the home, and more likely to be treated with epinephrine. Conclusions: Allergic reactions to peanut and tree nut are frequently severe, often occur on the first known exposure, and can become more severe over time.. food allergy| anaphylaxis| peanut| tree nuts|food| prevalence| sensitization| children| birth| skin.	JUL-2001	food allergy| anaphylaxis| peanut| tree nuts|food| prevalence| sensitization| children| birth| skin	Sicherer, SH; Furlong, TJ; Munoz-Furlong, A; Burks, AW; Sampson, HA	A voluntary registry for peanut and tree nut allergy: Characteristics of the first 5149 registrants		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	food allergy; anaphylaxis; peanut; tree nuts	FOOD; PREVALENCE; SENSITIZATION; CHILDREN; BIRTH; SKIN	Background: A voluntary registry of individuals with peanut and/or tree nut allergy was established in 1997 to learn more about these food allergies. Objective: The purpose of this study was to elucidate a variety of features of peanut and tree nut allergy among the first 5149 registry participants. Methods: The registry was established through use of a structured questionnaire distributed to all members of the Food Allergy and Anaphylaxis Network and to patients by allergists. Parental surrogates completed the forms for children under the age of 18 years. Results: Registrants were primarily children (89% of registrants were younger than 18 years of age: the median age was 5 years), reflecting the membership of the Network. Isolated peanut allergy was reported by 3482 registrants (68%), isolated tree nut allergy by 464 (9%), and allergy to both foods by 1203 (23%). Registrants were more likely to have been born in October, November, or December (odds ratio, 1.2; 95% CI, 1.18-1.23; P < .0001). The median age of reaction to peanut was 14 months, and the median age of reaction to tree nuts was 36 months; these represented the first known exposure for 74% and 68% of registrants, respectively. One half of the reactions involved more than 1 organ system, and more than 75% required treatment, frequently from medical personnel. Registrants with asthma were more likely than those without asthma to have severe reactions (33% vs 21%; P < .0001). In comparison with initial reactions, subsequent reactions due to accidental ingestion were more severe. more common outside the home, and more likely to be treated with epinephrine. Conclusions: Allergic reactions to peanut and tree nut are frequently severe, often occur on the first known exposure, and can become more severe over time.	27	217	2001	5		Allergy; Immunology
Seasonal analyses of air pollution and mortality in 100 US cities. Time series models relating short-term changes in air pollution levels to daily mortality counts typically assume that the effects of air pollution on the log relative rate of mortality do not vary with time. However, these short-term effects might plausibly vary by season. Changes in the sources of air pollution and meteorology can result in changes in characteristics of the air pollution mixture across seasons. The authors developed Bayesian semiparametric hierarchical models for estimating time-varying effects of pollution on mortality in multisite time series studies. The methods were applied to the database of the National Morbidity and Mortality Air Pollution Study, which includes data for 100 US cities, for the period 1987-2000. At the national level, a 10-mug/m(3) increase in particulate matter less than 10 mum in aerodynamic diameter at a 1-day lag was associated with 0.15% (95% posterior interval (PI): -0.08, 0.39), 0.14% (95% PI: -0.14, 0.42), 0.36% (95% PI: 0.11, 0.61), and 0.14% (95% PI: -0.06, 0.34) increases in mortality for winter, spring, summer, and fall, respectively. An analysis by geographic region found a strong seasonal pattern in the Northeast (with a peak in summer) and little seasonal variation in the southern regions of the country. These results provide useful information for understanding particle toxicity and guiding future analyses of particle constituent data.. air pollution| epidemiologic methods| models| statistical| mortality| seasons|particulate matter| time-series| response relationships| philadelphia| health| exposure| children| project| models| asthma.	MAR 15-2005	air pollution| epidemiologic methods| models| statistical| mortality| seasons|particulate matter| time-series| response relationships| philadelphia| health| exposure| children| project| models| asthma	Peng, RD; Dominici, F; Pastor-Barriuso, R; Zeger, SL; Samet, JM	Seasonal analyses of air pollution and mortality in 100 US cities		AMERICAN JOURNAL OF EPIDEMIOLOGY	air pollution; epidemiologic methods; models; statistical; mortality; seasons	PARTICULATE MATTER; TIME-SERIES; RESPONSE RELATIONSHIPS; PHILADELPHIA; HEALTH; EXPOSURE; CHILDREN; PROJECT; MODELS; ASTHMA	Time series models relating short-term changes in air pollution levels to daily mortality counts typically assume that the effects of air pollution on the log relative rate of mortality do not vary with time. However, these short-term effects might plausibly vary by season. Changes in the sources of air pollution and meteorology can result in changes in characteristics of the air pollution mixture across seasons. The authors developed Bayesian semiparametric hierarchical models for estimating time-varying effects of pollution on mortality in multisite time series studies. The methods were applied to the database of the National Morbidity and Mortality Air Pollution Study, which includes data for 100 US cities, for the period 1987-2000. At the national level, a 10-mug/m(3) increase in particulate matter less than 10 mum in aerodynamic diameter at a 1-day lag was associated with 0.15% (95% posterior interval (PI): -0.08, 0.39), 0.14% (95% PI: -0.14, 0.42), 0.36% (95% PI: 0.11, 0.61), and 0.14% (95% PI: -0.06, 0.34) increases in mortality for winter, spring, summer, and fall, respectively. An analysis by geographic region found a strong seasonal pattern in the Northeast (with a peak in summer) and little seasonal variation in the southern regions of the country. These results provide useful information for understanding particle toxicity and guiding future analyses of particle constituent data.	34	216	2005	10	10.1093/aje/kwi075	Public, Environmental & Occupational Health
Independent effects of intestinal parasites infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study. Background Why asthma is rare in rural subsistence societies is not clear. We tested the hypotheses that the risk of asthma is reduced by intestinal parasites or hepatitis A infection, and increased by exposure to dust-mite allergen or organophosphorus insecticides in urban and rural areas of Jimma, Ethiopia. Methods From 12876 individuals who took part in a study of asthma and atopy in urban and rural Jimma in 1996, we identified all who reported wheeze in the previous 12 months, and a random subsample of controls. In 1999, we assessed parasites in faecal samples, Der p 1 levels in bedding, hepatitis A antibodies, serum cholinesterase (a marker of organophosphorus exposure), total and specific serum IgE, and skin sensitisation to Dermatophagoides pteronyssinus in 205 cases and 399 controls aged over 16 years. The effects of parasitosis, Der p 1 level, hepatitis A seropositivity, and cholinesterase concentration on risk of wheeze, and the role of IgE and skin sensitisation in these associations, were analysed by multiple logistic regression. Findings The risk of wheeze was independently reduced by hookworm infection by an odds ratio of 0.48 (95% CI 0.24-0.93, p=0.03), increased in relation to Der p 1 level (odds ratio per quartile 1.26 [1.00-1.59], p=0.05), and was unrelated to hepatitis A seropositivity or cholinesterase concentration. In the urban population, D pteronyssinus skin sensitisation was more strongly related to wheeze (9.45 [5.03-17.75]) than in the rural areas (1.95 [0.58-6.61], p for interaction=0.017), where D pteronyssinus sensitisation was common, but unrelated to wheeze in the presence of high-intensity parasite infection. Interpretation High degrees of parasite infection might prevent asthma symptoms in atopic individuals.. exercise-induced bronchospasm| kenyan school-children| papua-new-guinea| house-dust mite| asthma| prevalence| urban| atopy| hookworm| association.	NOV 3-2001	exercise-induced bronchospasm| kenyan school-children| papua-new-guinea| house-dust mite| asthma| prevalence| urban| atopy| hookworm| association	Scrivener, S; Yemaneberhan, H; Zebenigus, M; Tilahun, D; Girma, S; Ali, S; McElroy, P; Custovic, A; Woodcock, A; Pritchard, D; Venn, A; Britton, J	Independent effects of intestinal parasites infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study		LANCET		EXERCISE-INDUCED BRONCHOSPASM; KENYAN SCHOOL-CHILDREN; PAPUA-NEW-GUINEA; HOUSE-DUST MITE; ASTHMA; PREVALENCE; URBAN; ATOPY; HOOKWORM; ASSOCIATION	Background Why asthma is rare in rural subsistence societies is not clear. We tested the hypotheses that the risk of asthma is reduced by intestinal parasites or hepatitis A infection, and increased by exposure to dust-mite allergen or organophosphorus insecticides in urban and rural areas of Jimma, Ethiopia. Methods From 12876 individuals who took part in a study of asthma and atopy in urban and rural Jimma in 1996, we identified all who reported wheeze in the previous 12 months, and a random subsample of controls. In 1999, we assessed parasites in faecal samples, Der p 1 levels in bedding, hepatitis A antibodies, serum cholinesterase (a marker of organophosphorus exposure), total and specific serum IgE, and skin sensitisation to Dermatophagoides pteronyssinus in 205 cases and 399 controls aged over 16 years. The effects of parasitosis, Der p 1 level, hepatitis A seropositivity, and cholinesterase concentration on risk of wheeze, and the role of IgE and skin sensitisation in these associations, were analysed by multiple logistic regression. Findings The risk of wheeze was independently reduced by hookworm infection by an odds ratio of 0.48 (95% CI 0.24-0.93, p=0.03), increased in relation to Der p 1 level (odds ratio per quartile 1.26 [1.00-1.59], p=0.05), and was unrelated to hepatitis A seropositivity or cholinesterase concentration. In the urban population, D pteronyssinus skin sensitisation was more strongly related to wheeze (9.45 [5.03-17.75]) than in the rural areas (1.95 [0.58-6.61], p for interaction=0.017), where D pteronyssinus sensitisation was common, but unrelated to wheeze in the presence of high-intensity parasite infection. Interpretation High degrees of parasite infection might prevent asthma symptoms in atopic individuals.	30	216	2001	7	10.1016/S0140-6736(01)06579-5	General & Internal Medicine
Relative scarcity of asthma and atopy among rural adolescents raised on a farm. We determined the prevalence of markers of atopy and asthma among 1,199 rural secondary school students ages 12 to 19 yr. Subjects identified as having been raised on a farm and half as many subjects without regular exposure to a farming environment from the same school class completed a respiratory symptom questionnaire and underwent allergy skin tests and a methacholine bronchoprovocation test. Current wheeze, airways hyperresponsiveness (AHR), and skin test positivity to inhaled allergens were all significantly less common among adolescents raised on the farm and these differences were especially pronounced in girls. After adjusting for gender and current smoking, the odds ratios for being raised on a farm were: 0.70 (95% CI 0.52 to 0.95) for current wheeze; 0.59 (95% CI 0.37 to 0.95) for asthma, defined as the concomitant occurrence of wheeze and AHR; and 0.58 (95% CI 0.46 to 0.75) for atopy defined as a positive reaction to any one of 24 common inhaled allergens. These associations were also not significantly altered by adjusting for the difference in the number of siblings.. respiratory-health-survey| hay-fever| allergic rhinitis| east-germany| prevalence| childhood| community| increase| schoolchildren| environment.	MAY-2000	respiratory-health-survey| hay-fever| allergic rhinitis| east-germany| prevalence| childhood| community| increase| schoolchildren| environment	Ernst, P; Cormier, Y	Relative scarcity of asthma and atopy among rural adolescents raised on a farm		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		RESPIRATORY-HEALTH-SURVEY; HAY-FEVER; ALLERGIC RHINITIS; EAST-GERMANY; PREVALENCE; CHILDHOOD; COMMUNITY; INCREASE; SCHOOLCHILDREN; ENVIRONMENT	We determined the prevalence of markers of atopy and asthma among 1,199 rural secondary school students ages 12 to 19 yr. Subjects identified as having been raised on a farm and half as many subjects without regular exposure to a farming environment from the same school class completed a respiratory symptom questionnaire and underwent allergy skin tests and a methacholine bronchoprovocation test. Current wheeze, airways hyperresponsiveness (AHR), and skin test positivity to inhaled allergens were all significantly less common among adolescents raised on the farm and these differences were especially pronounced in girls. After adjusting for gender and current smoking, the odds ratios for being raised on a farm were: 0.70 (95% CI 0.52 to 0.95) for current wheeze; 0.59 (95% CI 0.37 to 0.95) for asthma, defined as the concomitant occurrence of wheeze and AHR; and 0.58 (95% CI 0.46 to 0.75) for atopy defined as a positive reaction to any one of 24 common inhaled allergens. These associations were also not significantly altered by adjusting for the difference in the number of siblings.	26	216	2000	4		General & Internal Medicine; Respiratory System
Decline in lung function in the Busselton Health Study - The effects of asthma and cigarette smoking. Asthma in adults may be associated with chronic airflow obstruction, possibly resulting from airway disease in early life and/or a greater rate of decline in lung function in adult life compared with those with asthma. Treatment and cigarette smoking may also influence the rate of decline of lung function. The aim of this analysis was to examine the level and rate of decline in lung function in relationship to asthma and cigarette smoking in adults. Subjects (n = 9,317) had participated as adults (> 18 years) in one or more of the cross-sectional Busselton Health Surveys between 1966 and 1981 or in the follow-up study of 1994/1995. The effects of sex, doctor-diagnosed asthma, smoking status, and anthropometric data on the level and rate of decline in FEV1 were examined in a linear mixed effects model. At the age of 19 years, FEV1 was reduced in subjects with asthma but was similar in smokers and nonsmokers. Males, taller subjects, smokers, and subjects with asthma had greater declines in FEV1 with age. Smoking and asthma had additive but not multiplicative effects on decline. Thus, asthma is associated with reduced lung function at the beginning of adult life as well as an increased rate of decline during adult life.. asthma| epidemiology| lung function tests| smoking|obstructive pulmonary-disease| peripheral leukocyte count| air-flow obstruction| longitudinal decline| western-australia| childhood asthma| mild asthma| inflammation| adults| hyperresponsiveness.	JAN 15-2005	asthma| epidemiology| lung function tests| smoking|obstructive pulmonary-disease| peripheral leukocyte count| air-flow obstruction| longitudinal decline| western-australia| childhood asthma| mild asthma| inflammation| adults| hyperresponsiveness	James, AL; Palmer, LJ; Kicic, E; Maxwell, PS; Lagan, SE; Ryan, GF; Musk, AW	Decline in lung function in the Busselton Health Study - The effects of asthma and cigarette smoking		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; epidemiology; lung function tests; smoking	OBSTRUCTIVE PULMONARY-DISEASE; PERIPHERAL LEUKOCYTE COUNT; AIR-FLOW OBSTRUCTION; LONGITUDINAL DECLINE; WESTERN-AUSTRALIA; CHILDHOOD ASTHMA; MILD ASTHMA; INFLAMMATION; ADULTS; HYPERRESPONSIVENESS	Asthma in adults may be associated with chronic airflow obstruction, possibly resulting from airway disease in early life and/or a greater rate of decline in lung function in adult life compared with those with asthma. Treatment and cigarette smoking may also influence the rate of decline of lung function. The aim of this analysis was to examine the level and rate of decline in lung function in relationship to asthma and cigarette smoking in adults. Subjects (n = 9,317) had participated as adults (> 18 years) in one or more of the cross-sectional Busselton Health Surveys between 1966 and 1981 or in the follow-up study of 1994/1995. The effects of sex, doctor-diagnosed asthma, smoking status, and anthropometric data on the level and rate of decline in FEV1 were examined in a linear mixed effects model. At the age of 19 years, FEV1 was reduced in subjects with asthma but was similar in smokers and nonsmokers. Males, taller subjects, smokers, and subjects with asthma had greater declines in FEV1 with age. Smoking and asthma had additive but not multiplicative effects on decline. Thus, asthma is associated with reduced lung function at the beginning of adult life as well as an increased rate of decline during adult life.	38	215	2005	6	10.1164/rccm.200402-230OC	General & Internal Medicine; Respiratory System
"Population disparities in asthma. The prevalence of asthma in the United States is higher than in many other countries in the world. Asthma, the most common chronic disease of childhood in the United States, disproportionately burdens many socioeconomically disadvantaged urban communities. In this review we discuss hypotheses for between-country disparities in asthma prevalence, including differences in ""hygiene"" (e.g., family size, use of day care, early-life respiratory infection exposures, endotoxin and other farm-related exposures, microbial colonization of the infant bowel, exposure to parasites, and exposure to large domestic animal sources of allergen), diet, traffic pollution, and cigarette smoking. We present data on socioeconomic and ethnic disparities in asthma prevalence and morbidity in the United States and discuss environmental factors contributing to asthma disparities (e.g., housing conditions, indoor environmental exposures including allergens, traffic air pollution, disparities in treatment and access to care, and cigarette smoking). We discuss environmental influences on somatic growth (low birth weight, prematurity, and obesity) and their relevance to asthma disparities. The relevance of the hygiene hypothesis to the U.S. urban situation is reviewed. Finally, we discuss community-level factors contributing to asthma disparities.. children| hygiene hypothesis| smoking| allergens| traffic pollution| obesity|posttraumatic-stress-disorder| day-care attendance| small-area analysis| inner-city asthma| lower respiratory illness| coronary heart-disease| body-mass index| total serum ige| childhood asthma| united-states."	2005	children| hygiene hypothesis| smoking| allergens| traffic pollution| obesity|posttraumatic-stress-disorder| day-care attendance| small-area analysis| inner-city asthma| lower respiratory illness| coronary heart-disease| body-mass index| total serum ige| childhood asthma| united-states	Gold, DR; Wright, R	Population disparities in asthma		ANNUAL REVIEW OF PUBLIC HEALTH	children; hygiene hypothesis; smoking; allergens; traffic pollution; obesity	POSTTRAUMATIC-STRESS-DISORDER; DAY-CARE ATTENDANCE; SMALL-AREA ANALYSIS; INNER-CITY ASTHMA; LOWER RESPIRATORY ILLNESS; CORONARY HEART-DISEASE; BODY-MASS INDEX; TOTAL SERUM IGE; CHILDHOOD ASTHMA; UNITED-STATES	"The prevalence of asthma in the United States is higher than in many other countries in the world. Asthma, the most common chronic disease of childhood in the United States, disproportionately burdens many socioeconomically disadvantaged urban communities. In this review we discuss hypotheses for between-country disparities in asthma prevalence, including differences in ""hygiene"" (e.g., family size, use of day care, early-life respiratory infection exposures, endotoxin and other farm-related exposures, microbial colonization of the infant bowel, exposure to parasites, and exposure to large domestic animal sources of allergen), diet, traffic pollution, and cigarette smoking. We present data on socioeconomic and ethnic disparities in asthma prevalence and morbidity in the United States and discuss environmental factors contributing to asthma disparities (e.g., housing conditions, indoor environmental exposures including allergens, traffic air pollution, disparities in treatment and access to care, and cigarette smoking). We discuss environmental influences on somatic growth (low birth weight, prematurity, and obesity) and their relevance to asthma disparities. The relevance of the hygiene hypothesis to the U.S. urban situation is reviewed. Finally, we discuss community-level factors contributing to asthma disparities."	155	215	2005	25	10.1146/annurev.publhealth.26.021304.144528	Public, Environmental & Occupational Health
Mechanisms of interleukin-10-mediated immune suppression. Specific immune suppression and induction of anergy are essential processes in the regulation and circumvention of immune defence. Interleukin-10 (IL-10), a suppressor cytokine of T-cell proliferative and cytokine responses, plays a key regulatory role in tolerizing exogenous antigens during specific immunotherapy (SIT) of allergy and natural exposure to antigens. Specific T-cell tolerance is directed against the T-cell epitopes of an antigen and characterized by suppressed proliferative and T helper type 1 (Th1) and type 2 (Th2) cytokine responses. IL-10 elicits tolerance in T cells by selective inhibition of the CD28 co-stimulatory pathway and thereby controls suppression and development of antigen-specific immunity. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors and which therefore depend on CD28 co-stimulation. T cells receiving a strong signal from the T-cell receptor alone, and thus not requiring CD28 co-stimulation, are not affected by IL-10. IL-10 inhibits CD28 tyrosine phosphorylation, the initial step of the CD28 signalling pathway, and consequently the phosphatidylinositol 3-kinase p85 binding to CD28. Together these results demonstrate that IL-10-induced selective inhibition of the CD28 co-stimulatory pathway acts as a decisive mechanism in determining whether a T cell will contribute to an immune response or become anergic.. bee venom phospholipase-a2| t-cell epitope| peripheral-blood eosinophils| inhibits cytokine production| human lymphocytes-t| phosphatidylinositol 3-kinase| in-vitro| b-cell| tyrosine phosphorylation| differential regulation.	JUN-2001	bee venom phospholipase-a2| t-cell epitope| peripheral-blood eosinophils| inhibits cytokine production| human lymphocytes-t| phosphatidylinositol 3-kinase| in-vitro| b-cell| tyrosine phosphorylation| differential regulation	Akdis, CA; Blaser, K	Mechanisms of interleukin-10-mediated immune suppression		IMMUNOLOGY		BEE VENOM PHOSPHOLIPASE-A2; T-CELL EPITOPE; PERIPHERAL-BLOOD EOSINOPHILS; INHIBITS CYTOKINE PRODUCTION; HUMAN LYMPHOCYTES-T; PHOSPHATIDYLINOSITOL 3-KINASE; IN-VITRO; B-CELL; TYROSINE PHOSPHORYLATION; DIFFERENTIAL REGULATION	Specific immune suppression and induction of anergy are essential processes in the regulation and circumvention of immune defence. Interleukin-10 (IL-10), a suppressor cytokine of T-cell proliferative and cytokine responses, plays a key regulatory role in tolerizing exogenous antigens during specific immunotherapy (SIT) of allergy and natural exposure to antigens. Specific T-cell tolerance is directed against the T-cell epitopes of an antigen and characterized by suppressed proliferative and T helper type 1 (Th1) and type 2 (Th2) cytokine responses. IL-10 elicits tolerance in T cells by selective inhibition of the CD28 co-stimulatory pathway and thereby controls suppression and development of antigen-specific immunity. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors and which therefore depend on CD28 co-stimulation. T cells receiving a strong signal from the T-cell receptor alone, and thus not requiring CD28 co-stimulation, are not affected by IL-10. IL-10 inhibits CD28 tyrosine phosphorylation, the initial step of the CD28 signalling pathway, and consequently the phosphatidylinositol 3-kinase p85 binding to CD28. Together these results demonstrate that IL-10-induced selective inhibition of the CD28 co-stimulatory pathway acts as a decisive mechanism in determining whether a T cell will contribute to an immune response or become anergic.	66	215	2001	6	10.1046/j.1365-2567.2001.01235.x	Immunology
Epidemiologic risks for food allergy. This article reviews possible risk factors and theories for the development of food allergy. It is noted that previous strategies to prevent food allergy through allergen avoidance during pregnancy, breast-feeding, and infancy have more recently been called into question. Alternative hypotheses are examined with respect to food allergy, namely the hygiene hypothesis, the dietary fat hypothesis, the antioxidant hypothesis, and the vitamin D hypotheses. An alternative hypothesis is proposed, suggesting that sensitization to allergen occurs through environmental exposure to allergen through the skin and that consumption of food allergen induces oral tolerance. This hypothesis provides a possible explanation for the close link between eczema and the development of food allergies. It also suggests novel interventional strategies to prevent the development of food allergies.. risk factors| food allergy| allergen|atopic-dermatitis| peanut allergy| vitamin-d| questionnaire survey| oral tolerance| nut allergy| skin prick| follow-up| children| infant.	JUN-2008	risk factors| food allergy| allergen|atopic-dermatitis| peanut allergy| vitamin-d| questionnaire survey| oral tolerance| nut allergy| skin prick| follow-up| children| infant	Lack, G	Epidemiologic risks for food allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	risk factors; food allergy; allergen	ATOPIC-DERMATITIS; PEANUT ALLERGY; VITAMIN-D; QUESTIONNAIRE SURVEY; ORAL TOLERANCE; NUT ALLERGY; SKIN PRICK; FOLLOW-UP; CHILDREN; INFANT	This article reviews possible risk factors and theories for the development of food allergy. It is noted that previous strategies to prevent food allergy through allergen avoidance during pregnancy, breast-feeding, and infancy have more recently been called into question. Alternative hypotheses are examined with respect to food allergy, namely the hygiene hypothesis, the dietary fat hypothesis, the antioxidant hypothesis, and the vitamin D hypotheses. An alternative hypothesis is proposed, suggesting that sensitization to allergen occurs through environmental exposure to allergen through the skin and that consumption of food allergen induces oral tolerance. This hypothesis provides a possible explanation for the close link between eczema and the development of food allergies. It also suggests novel interventional strategies to prevent the development of food allergies.	52	214	2008	6	10.1016/j.jaci.2008.04.032	Allergy; Immunology
"Anisakis simplex: from obscure infectious worm to inducer of immune hyersensitivity. Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (""gastroallergic anisakiasis""), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, coveting immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.. excretory-secretory products| pseudoterranova-decipiens nematoda| gastro-allergic anisakiasis| serine-protease inhibitor| ani s 1| major allergen| ascaris-suum| antibody repertoire| molecular-cloning| cross-reactivity."	APR-2008	excretory-secretory products| pseudoterranova-decipiens nematoda| gastro-allergic anisakiasis| serine-protease inhibitor| ani s 1| major allergen| ascaris-suum| antibody repertoire| molecular-cloning| cross-reactivity	Audicana, MT; Kennedy, MW	Anisakis simplex: from obscure infectious worm to inducer of immune hyersensitivity		CLINICAL MICROBIOLOGY REVIEWS		EXCRETORY-SECRETORY PRODUCTS; PSEUDOTERRANOVA-DECIPIENS NEMATODA; GASTRO-ALLERGIC ANISAKIASIS; SERINE-PROTEASE INHIBITOR; ANI S 1; MAJOR ALLERGEN; ASCARIS-SUUM; ANTIBODY REPERTOIRE; MOLECULAR-CLONING; CROSS-REACTIVITY	"Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (""gastroallergic anisakiasis""), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, coveting immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive."	281	214	2008	21	10.1128/CMR.00012-07	Microbiology
Particulate matter properties and health effects: consistency of epidemiological and toxicological studies. Identifying the ambient particulate matter (PM) fractions or constituents, critically involved in eliciting adverse health effects, is crucial to the implementation of more cost-efficient abatement strategies to improve air quality. This review focuses on the importance of different particle properties for PM-induced effects, and whether there is consistency in the results from epidemiological and experimental studies. An evident problem for such comparisons is that epidemiological and experimental data on the effects of specific components of ambient PM are limited. Despite this, some conclusions can be drawn. With respect to the importance of the PM size-fractions experimental and epidemiological studies are somewhat conflicting, but there seems to be a certain consistency in that the coarse fraction (PM10-2.5) has an effect that should not be neglected. Better exposure characterization may improve the consistency between the results from experimental and epidemiological studies, in particular for ultrafine particles. Experimental data indicate that surface area is an important metric, but composition may play an even greater role in eliciting effects. The consistency between epidemiological and experimental findings for specific PM-components appears most convincing for metals, which seem to be important for the development of both pulmonary and cardiovascular disease. Metals may also be involved in PM-induced allergic sensitization, but the epidemiological evidence for this is scarce. Soluble organic compounds appear to be implicated in PM-induced allergy and cancer, but the data from epidemiological studies are insufficient for any conclusions. The present review suggests that there may be a need for improvements in research designs. In particular, there is a need for better exposure assessments in epidemiological investigations, whereas experimental data would benefit from an improved comparability of studies. Combined experimental and epidemiological investigations may also help answer some of the unresolved issues.. ambient particulate matter| epidemiology| health effects| particle composition| toxicology|diesel exhaust particles| airway epithelial-cells| polycyclic aromatic-hydrocarbons| coronary-heart-disease| insoluble iridium particles| long-term exposure| nf-kappa-b| ambient air| in-vitro| daily mortality.	OCT-2006	ambient particulate matter| epidemiology| health effects| particle composition| toxicology|diesel exhaust particles| airway epithelial-cells| polycyclic aromatic-hydrocarbons| coronary-heart-disease| insoluble iridium particles| long-term exposure| nf-kappa-b| ambient air| in-vitro| daily mortality	Schwarze, PE; Ovrevik, J; Lag, M; Refsnes, M; Nafstad, P; Hetland, RB; Dybing, E	Particulate matter properties and health effects: consistency of epidemiological and toxicological studies		HUMAN & EXPERIMENTAL TOXICOLOGY	ambient particulate matter; epidemiology; health effects; particle composition; toxicology	DIESEL EXHAUST PARTICLES; AIRWAY EPITHELIAL-CELLS; POLYCYCLIC AROMATIC-HYDROCARBONS; CORONARY-HEART-DISEASE; INSOLUBLE IRIDIUM PARTICLES; LONG-TERM EXPOSURE; NF-KAPPA-B; AMBIENT AIR; IN-VITRO; DAILY MORTALITY	Identifying the ambient particulate matter (PM) fractions or constituents, critically involved in eliciting adverse health effects, is crucial to the implementation of more cost-efficient abatement strategies to improve air quality. This review focuses on the importance of different particle properties for PM-induced effects, and whether there is consistency in the results from epidemiological and experimental studies. An evident problem for such comparisons is that epidemiological and experimental data on the effects of specific components of ambient PM are limited. Despite this, some conclusions can be drawn. With respect to the importance of the PM size-fractions experimental and epidemiological studies are somewhat conflicting, but there seems to be a certain consistency in that the coarse fraction (PM10-2.5) has an effect that should not be neglected. Better exposure characterization may improve the consistency between the results from experimental and epidemiological studies, in particular for ultrafine particles. Experimental data indicate that surface area is an important metric, but composition may play an even greater role in eliciting effects. The consistency between epidemiological and experimental findings for specific PM-components appears most convincing for metals, which seem to be important for the development of both pulmonary and cardiovascular disease. Metals may also be involved in PM-induced allergic sensitization, but the epidemiological evidence for this is scarce. Soluble organic compounds appear to be implicated in PM-induced allergy and cancer, but the data from epidemiological studies are insufficient for any conclusions. The present review suggests that there may be a need for improvements in research designs. In particular, there is a need for better exposure assessments in epidemiological investigations, whereas experimental data would benefit from an improved comparability of studies. Combined experimental and epidemiological investigations may also help answer some of the unresolved issues.	210	214	2006	21	10.1177/096032706072520	Toxicology
The role of protease activation of inflammation in allergic respiratory diseases. Extracellular endogenous proteases, as well as exogenous proteases from mites and molds, react with cell-surface receptors in the airways to generate leukocyte infiltration and to amplify the response to allergens. Stimulation leads to increased intracellular Ca++ and gene transcription. The most thoroughly investigated receptors, protease-activated receptors (PARs), are 7-transmembrane proteins coupled to G proteins. PARs are widely distributed on the cells of the airways, where they contribute to the inflammation characteristic of allergic diseases. PAR stimulation of epithelial cells opens tight junctions, causes desquamation, And produces cytokines, chemokines, and growth factors. They degranulate eosinophils and mast cells. Proteases contract bronchial smooth muscle and cause it to proliferate. PARs also promote maturation, proliferation, and collagen production of fibroblast precursors and mature fibroblasts. PAR-2, apparently the most important of the 4 PARs that have been characterized, is increased on the epithelium of patients with asthma. Trypsin, a product of injured epithelial cells, and mast cell tryptase are potent activators of PAR-2. Mast cell chymase activates PAR-I. Proteases from mites and molds appear to act through similar receptors. They amplify IgE production to allergens, degranulate eosinophils, and can generate inflammation, even in the absence of IgE. Proteases produced by Aspergillus species to support its growth are presumably responsible for the exuberant IgE, IgG, and granulomatous response of allergic bronchopulmonary aspergillosis. Similar proteases from molds germinating on the respiratory mucosa have been recently been implicated in the pathogenesis of chronic hyperplastic rhinitis and polyps and, by extension, of intrinsic asthma. Finally, proteases from mites and fungi growing in damp, water-damaged buildings might be the basis for the increased prevalence in these buildings of rhinitis, asthma, and other respiratory diseases. Future research promises to promote our understanding of the pathogenesis of allergic respiratory diseases and point the way to new therapies.. allergen| proteases| allergic inflammation| asthma| sinusitis|mast-cell tryptase| airway smooth-muscle| dust-mite allergen| lung epithelial-cells| severe alpha(1)-antitrypsin deficiency| induce cytokine release| factor xa| endothelial-cells| dermatophagoides-farinae| aspergillus-fumigatus.	NOV-2004	allergen| proteases| allergic inflammation| asthma| sinusitis|mast-cell tryptase| airway smooth-muscle| dust-mite allergen| lung epithelial-cells| severe alpha(1)-antitrypsin deficiency| induce cytokine release| factor xa| endothelial-cells| dermatophagoides-farinae| aspergillus-fumigatus	Reed, CE; Kita, H	The role of protease activation of inflammation in allergic respiratory diseases		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen; proteases; allergic inflammation; asthma; sinusitis	MAST-CELL TRYPTASE; AIRWAY SMOOTH-MUSCLE; DUST-MITE ALLERGEN; LUNG EPITHELIAL-CELLS; SEVERE ALPHA(1)-ANTITRYPSIN DEFICIENCY; INDUCE CYTOKINE RELEASE; FACTOR XA; ENDOTHELIAL-CELLS; DERMATOPHAGOIDES-FARINAE; ASPERGILLUS-FUMIGATUS	Extracellular endogenous proteases, as well as exogenous proteases from mites and molds, react with cell-surface receptors in the airways to generate leukocyte infiltration and to amplify the response to allergens. Stimulation leads to increased intracellular Ca++ and gene transcription. The most thoroughly investigated receptors, protease-activated receptors (PARs), are 7-transmembrane proteins coupled to G proteins. PARs are widely distributed on the cells of the airways, where they contribute to the inflammation characteristic of allergic diseases. PAR stimulation of epithelial cells opens tight junctions, causes desquamation, And produces cytokines, chemokines, and growth factors. They degranulate eosinophils and mast cells. Proteases contract bronchial smooth muscle and cause it to proliferate. PARs also promote maturation, proliferation, and collagen production of fibroblast precursors and mature fibroblasts. PAR-2, apparently the most important of the 4 PARs that have been characterized, is increased on the epithelium of patients with asthma. Trypsin, a product of injured epithelial cells, and mast cell tryptase are potent activators of PAR-2. Mast cell chymase activates PAR-I. Proteases from mites and molds appear to act through similar receptors. They amplify IgE production to allergens, degranulate eosinophils, and can generate inflammation, even in the absence of IgE. Proteases produced by Aspergillus species to support its growth are presumably responsible for the exuberant IgE, IgG, and granulomatous response of allergic bronchopulmonary aspergillosis. Similar proteases from molds germinating on the respiratory mucosa have been recently been implicated in the pathogenesis of chronic hyperplastic rhinitis and polyps and, by extension, of intrinsic asthma. Finally, proteases from mites and fungi growing in damp, water-damaged buildings might be the basis for the increased prevalence in these buildings of rhinitis, asthma, and other respiratory diseases. Future research promises to promote our understanding of the pathogenesis of allergic respiratory diseases and point the way to new therapies.	134	214	2004	12	10.1016/j.jaci.2004.07.060	Allergy; Immunology
Characterization and immunobiology of house dust mite allergens. The examination of house dust mite extracts has indicated that over 30 different proteins can induce IgE antibody in patients allergic to the house dust mite. There are however dominant specificities especially the group 1 and 2 allergens which can account for much of the allergenicity of extracts. Of the 19 denominated allergens, the major IgE binding has been reported for the group 1, 2, 3, 9, 11, 14 and 15 allergens. The high-molecular-weight group 11, 14 and 15 allergens have only recently been described and although high IgE binding has been anticipated from immunoblotting, there is a need for considerable corroboration. Similarly, the study of the group 3 and 9 serine protease allergens has been incomplete. The group 4, 5, 7 and 8 allergens have shown intermediate IgE binding and the group 10 tropomyosins are of interest because of their potential cross-reactivity with allergen from disparate species. Although the progress with the production of recombinant group 1 allergens has been recent, many of the allergens can be produced as high IgE-binding polypeptides. The tertiary structure of the group 2 allergens has been determined from recombinant proteins and they are an excellent model for the investigation of modified allergens. An unexpected property of the group 1, 2 and 3 allergens has been the high degree of polymorphism found by cDNA analysis. It has however been possible to identify sequences to represent the variation in the natural allergens. The group 7 and 14 allergens show secondary modifications which vary in different extracts creating batch variation. While some estimate of the importance of allergens can be obtained from IgE binding, few analyses of T-cell responses have been made and these regulate both the development of, and the protection from sensitization. Copyright (C) 2002 S. Karger AG, Basel.. house dust mite| allergen| ige| t cell| recombinant mite allergens|der-p-i| t-cell responses| site-directed mutagenesis| human ige antibodies| cysteine protease activity| glutathione-s-transferase| molecular-weight allergen| major secretory protein| acid-binding proteins| group-iii allergen.	SEP-2002	house dust mite| allergen| ige| t cell| recombinant mite allergens|der-p-i| t-cell responses| site-directed mutagenesis| human ige antibodies| cysteine protease activity| glutathione-s-transferase| molecular-weight allergen| major secretory protein| acid-binding proteins| group-iii allergen	Thomas, WR; Smith, WA; Hales, BJ; Mills, KL; O'Brien, RM	Characterization and immunobiology of house dust mite allergens		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	house dust mite; allergen; IgE; T cell; recombinant mite allergens	DER-P-I; T-CELL RESPONSES; SITE-DIRECTED MUTAGENESIS; HUMAN IGE ANTIBODIES; CYSTEINE PROTEASE ACTIVITY; GLUTATHIONE-S-TRANSFERASE; MOLECULAR-WEIGHT ALLERGEN; MAJOR SECRETORY PROTEIN; ACID-BINDING PROTEINS; GROUP-III ALLERGEN	The examination of house dust mite extracts has indicated that over 30 different proteins can induce IgE antibody in patients allergic to the house dust mite. There are however dominant specificities especially the group 1 and 2 allergens which can account for much of the allergenicity of extracts. Of the 19 denominated allergens, the major IgE binding has been reported for the group 1, 2, 3, 9, 11, 14 and 15 allergens. The high-molecular-weight group 11, 14 and 15 allergens have only recently been described and although high IgE binding has been anticipated from immunoblotting, there is a need for considerable corroboration. Similarly, the study of the group 3 and 9 serine protease allergens has been incomplete. The group 4, 5, 7 and 8 allergens have shown intermediate IgE binding and the group 10 tropomyosins are of interest because of their potential cross-reactivity with allergen from disparate species. Although the progress with the production of recombinant group 1 allergens has been recent, many of the allergens can be produced as high IgE-binding polypeptides. The tertiary structure of the group 2 allergens has been determined from recombinant proteins and they are an excellent model for the investigation of modified allergens. An unexpected property of the group 1, 2 and 3 allergens has been the high degree of polymorphism found by cDNA analysis. It has however been possible to identify sequences to represent the variation in the natural allergens. The group 7 and 14 allergens show secondary modifications which vary in different extracts creating batch variation. While some estimate of the importance of allergens can be obtained from IgE binding, few analyses of T-cell responses have been made and these regulate both the development of, and the protection from sensitization. Copyright (C) 2002 S. Karger AG, Basel.	196	214	2002	18	10.1159/000065179	Allergy; Immunology
Endotoxin exposure in allergy and asthma: Reconciling a paradox. Well-established evidence links endotoxin exposure, especially in the workplace, to airways disease. Endotoxin can increase disease severity by acting as a natural adjuvant to augment asthma and atopic inflammation. Recent studies suggest that it can even act on its own, causing a distinct endotoxic form of asthma. Other studies, however, contradict the paradigm that endotoxin's influence is solely a negative one. Epidemiologic associations of environmental endotoxin exposure with allergy and asthma prevention are consistent with hygiene hypothesis associations of other microbial exposures or infections with a lower incidence of atopic disease. Currently, microbe-derived products are being developed as potential therapies for allergy and asthma. Thus it is an ideal time to consider endotoxin as a prototype of a natural intervention with microbial components. Nature's ongoing experiment with endotoxin can provide clues for the development of effective and safe microbe-based products for disease treatment and prevention. This article will discuss (1) conventional paradigms in which endotoxin-induced immune modulation by T(H)1-type induction leads to mitigation of T(H)2-type immune development, allergen sensitization, and atopic inflammation; (2) newer concepts of T(H)1-type immune responses that may provide additional asthma-protective effects by preventing airways remodeling; (3) home and environmental features that significantly contribute to endotoxin exposure; (4) different aspects of asthma mediated by endotoxin exposure; and (5) how to understand endotoxin's paradoxical nature of serving as both friend and foe.. allergy| asthma| therapy| prevention| endotoxin| lps| infection| hygiene| ifn-gamma| il-12| t(h)1|cd4(+) t-cells| growth-factor-beta| induced airway hyperresponsiveness| stimulatory factor interleukin-12| interferon-gamma production| grass-pollen immunotherapy| hay-fever| messenger-rna| collagen-synthesis| inhaled endotoxin.	MAR-2002	allergy| asthma| therapy| prevention| endotoxin| lps| infection| hygiene| ifn-gamma| il-12| t(h)1|cd4(+) t-cells| growth-factor-beta| induced airway hyperresponsiveness| stimulatory factor interleukin-12| interferon-gamma production| grass-pollen immunotherapy| hay-fever| messenger-rna| collagen-synthesis| inhaled endotoxin	Liu, AH	Endotoxin exposure in allergy and asthma: Reconciling a paradox		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; asthma; therapy; prevention; endotoxin; LPS; infection; hygiene; IFN-gamma; IL-12; T(H)1	CD4(+) T-CELLS; GROWTH-FACTOR-BETA; INDUCED AIRWAY HYPERRESPONSIVENESS; STIMULATORY FACTOR INTERLEUKIN-12; INTERFERON-GAMMA PRODUCTION; GRASS-POLLEN IMMUNOTHERAPY; HAY-FEVER; MESSENGER-RNA; COLLAGEN-SYNTHESIS; INHALED ENDOTOXIN	Well-established evidence links endotoxin exposure, especially in the workplace, to airways disease. Endotoxin can increase disease severity by acting as a natural adjuvant to augment asthma and atopic inflammation. Recent studies suggest that it can even act on its own, causing a distinct endotoxic form of asthma. Other studies, however, contradict the paradigm that endotoxin's influence is solely a negative one. Epidemiologic associations of environmental endotoxin exposure with allergy and asthma prevention are consistent with hygiene hypothesis associations of other microbial exposures or infections with a lower incidence of atopic disease. Currently, microbe-derived products are being developed as potential therapies for allergy and asthma. Thus it is an ideal time to consider endotoxin as a prototype of a natural intervention with microbial components. Nature's ongoing experiment with endotoxin can provide clues for the development of effective and safe microbe-based products for disease treatment and prevention. This article will discuss (1) conventional paradigms in which endotoxin-induced immune modulation by T(H)1-type induction leads to mitigation of T(H)2-type immune development, allergen sensitization, and atopic inflammation; (2) newer concepts of T(H)1-type immune responses that may provide additional asthma-protective effects by preventing airways remodeling; (3) home and environmental features that significantly contribute to endotoxin exposure; (4) different aspects of asthma mediated by endotoxin exposure; and (5) how to understand endotoxin's paradoxical nature of serving as both friend and foe.	161	214	2002	14	10.1067/mai.2002.122157	Allergy; Immunology
Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Background An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma. Methods Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge. Results Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO. Conclusions Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.. respiratory-syncytial-virus| ventilation maldistribution| viral-infections| reference ranges| age 13| infancy| sensitization| children| risk| spirometry.	DEC-2010	respiratory-syncytial-virus| ventilation maldistribution| viral-infections| reference ranges| age 13| infancy| sensitization| children| risk| spirometry	Sigurs, N; Aljassim, F; Kjellman, B; Robinson, PD; Sigurbergsson, F; Bjarnason, R; Gustafsson, PM	Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life		THORAX		RESPIRATORY-SYNCYTIAL-VIRUS; VENTILATION MALDISTRIBUTION; VIRAL-INFECTIONS; REFERENCE RANGES; AGE 13; INFANCY; SENSITIZATION; CHILDREN; RISK; SPIROMETRY	Background An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma. Methods Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge. Results Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO. Conclusions Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.	38	213	2010	8	10.1136/thx.2009.121582	Respiratory System
Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Background: Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals. Methods: Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function ( forced expiratory volume in 1 s (FEV(1)), mid forced expiratory flow (FEF(25-75))) and bronchial responsiveness were made at 7-9 years of age. Results: Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV(1) per mu mol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 % FEV(1) per mmol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes. Conclusions: The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.. preschool-children| high-risk| asthma| infants| birth| sensitization| patterns| exposure| sounds| cohort.	NOV-2008	preschool-children| high-risk| asthma| infants| birth| sensitization| patterns| exposure| sounds| cohort	Henderson, J; Granell, R; Heron, J; Sherriff, A; Simpson, A; Woodcock, A; Strachan, DP; Shaheen, SO; Sterne, JAC	Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood		THORAX		PRESCHOOL-CHILDREN; HIGH-RISK; ASTHMA; INFANTS; BIRTH; SENSITIZATION; PATTERNS; EXPOSURE; SOUNDS; COHORT	Background: Patterns of wheezing during early childhood may indicate differences in aetiology and prognosis of respiratory illnesses. Improved characterisation of wheezing phenotypes could lead to the identification of environmental influences on the development of asthma and airway diseases in predisposed individuals. Methods: Data collected on wheezing at seven time points from birth to 7 years from 6265 children in a longitudinal birth cohort (the ALSPAC study) were analysed. Latent class analysis was used to assign phenotypes based on patterns of wheezing. Measures of atopy, airway function ( forced expiratory volume in 1 s (FEV(1)), mid forced expiratory flow (FEF(25-75))) and bronchial responsiveness were made at 7-9 years of age. Results: Six phenotypes were identified. The strongest associations with atopy and airway responsiveness were found for intermediate onset (18 months) wheezing (OR for atopy 8.36, 95% CI 5.2 to 13.4; mean difference in dose response to methacholine 1.76, 95% CI 1.41 to 2.12 %FEV(1) per mu mol, compared with infrequent/never wheeze phenotype). Late onset wheezing (after 42 months) was also associated with atopy (OR 6.6, 95% CI 4.7 to 9.4) and airway responsiveness (mean difference 1.61, 95% CI 1.37 to 1.85 % FEV(1) per mmol). Transient and prolonged early wheeze were not associated with atopy but were weakly associated with increased airway responsiveness and persistent wheeze had intermediate associations with these outcomes. Conclusions: The wheezing phenotypes most strongly associated with atopy and airway responsiveness were characterised by onset after age 18 months. This has potential implications for the timing of environmental influences on the initiation of atopic wheezing in early childhood.	36	213	2008	7	10.1136/thx.2007.093187	Respiratory System
The mechanisms, diagnosis, and management of severe asthma in adults. There has been a recent increase in the prevalence of asthma worldwide; however, the 5-10% of patients with severe disease account for a substantial proportion of the health costs. Although most asthma cases can be satisfactorily managed with a combination of anti-inflammatory drugs and bronchodilators, patients who remain symptomatic despite maximum combination treatment represent a heterogeneous group consisting of those who are under-treated or non-adherent with their prescribed medication. After excluding under-treatment and poor compliance, corticosteroid refractory asthma can be identified as a subphenotype characterised by a heightened neutrophilic airway inflammatory response in the presence or absence of eosinophils, with evidence of increased tissue injury and remodelling. Although a wide range of environmental factors such as allergens, smoking, air pollution, infection, hormones, and specific drugs can contribute to this phenotype, other features associated with changes in the airway inflammatory response should be taken into account. Aberrant communication between an injured airway epithelium and underlying mesenchyme contributes to disease chronicity and refractoriness to corticosteroids. The importance of identifying underlying causative factors and the recent introduction of novel therapeutic approaches, including the targeting of immunoglobulin E and tumour necrosis factor a with biological agents, emphasise the need for careful phenotyping of patients with severe disease to target improved management of the individual patient's needs.. lung-function decline| severe persistent asthma| necrosis-factor-alpha| to-treat asthma| dose intravenous immunoglobulin| placebo-controlled trial| growth-factor receptor| churg-strauss-syndrome| airway smooth-muscle| quality-of-life.	AUG-SEP-2006	lung-function decline| severe persistent asthma| necrosis-factor-alpha| to-treat asthma| dose intravenous immunoglobulin| placebo-controlled trial| growth-factor receptor| churg-strauss-syndrome| airway smooth-muscle| quality-of-life	Holgate, ST; Polosa, R	The mechanisms, diagnosis, and management of severe asthma in adults		LANCET		LUNG-FUNCTION DECLINE; SEVERE PERSISTENT ASTHMA; NECROSIS-FACTOR-ALPHA; TO-TREAT ASTHMA; DOSE INTRAVENOUS IMMUNOGLOBULIN; PLACEBO-CONTROLLED TRIAL; GROWTH-FACTOR RECEPTOR; CHURG-STRAUSS-SYNDROME; AIRWAY SMOOTH-MUSCLE; QUALITY-OF-LIFE	There has been a recent increase in the prevalence of asthma worldwide; however, the 5-10% of patients with severe disease account for a substantial proportion of the health costs. Although most asthma cases can be satisfactorily managed with a combination of anti-inflammatory drugs and bronchodilators, patients who remain symptomatic despite maximum combination treatment represent a heterogeneous group consisting of those who are under-treated or non-adherent with their prescribed medication. After excluding under-treatment and poor compliance, corticosteroid refractory asthma can be identified as a subphenotype characterised by a heightened neutrophilic airway inflammatory response in the presence or absence of eosinophils, with evidence of increased tissue injury and remodelling. Although a wide range of environmental factors such as allergens, smoking, air pollution, infection, hormones, and specific drugs can contribute to this phenotype, other features associated with changes in the airway inflammatory response should be taken into account. Aberrant communication between an injured airway epithelium and underlying mesenchyme contributes to disease chronicity and refractoriness to corticosteroids. The importance of identifying underlying causative factors and the recent introduction of novel therapeutic approaches, including the targeting of immunoglobulin E and tumour necrosis factor a with biological agents, emphasise the need for careful phenotyping of patients with severe disease to target improved management of the individual patient's needs.	162	213	2006	18	10.1016/S0140-6736(06)69288-X	General & Internal Medicine
Interaction of mite allergens Der P3 and Der P9 with protease-activated receptor-2 expressed by lung epithelial cells. The respiratory epithelium represents the first barrier encountered by airborne Ags. Two major dust mite Ags, Der p3 and Der p9, are serine proteases that may activate lung epithelial cells by interaction with the protease-activated receptor 2 (PAR-2). In this study both Der p3 and Der p9 cleaved the peptide corresponding to the N terminus of PAR-2 at the activation site. Both Ags sequentially stimulated phosphoinositide hydrolysis, transient cytosolic Ca2+ mobilization, and release of GM-CSF and eotaxin in human pulmonary epithelial cells. These responses were similar to those observed with trypsin and a specific PAR-2 agonist and were related to the serine protease activity of Der p3 and Der p9. Cell exposure to the Ags resulted in a refractory period, indicating that a PAR had been cleaved. Partial desensitization to Der p3 and Der p9 by the PAR-2 agonist suggested that PAR-2 was one target of the Ags. However, PAR-2 was not the only target, because the PAR-2 agonist caused less desensitization to Der p3 and Der p9 than did trypsin. A phospholipase C inhibitor prevented the cytokine-releasing effect of the PAR-2 agonist and abolished or reduced (> 70%) the cytokine-releasing effects of Der p3 and Der p9. Our results suggest that Der p 3 and Der p9 may induce a nonallergic inflammatory response in the airways through the release of proinflammatory cytokines from the bronchial epithelium and that this effect is at least in part mediated by PAR-2.. group-iii allergen| dermatophagoides-pteronyssinus| airway hyperresponsiveness| thrombin receptors| gene-expression| atopic asthma| release| cloning| keratinocytes| inflammation.	JUL 15-2001	group-iii allergen| dermatophagoides-pteronyssinus| airway hyperresponsiveness| thrombin receptors| gene-expression| atopic asthma| release| cloning| keratinocytes| inflammation	Sun, G; Stacey, MA; Schmidt, M; Mori, L; Mattoli, S	Interaction of mite allergens Der P3 and Der P9 with protease-activated receptor-2 expressed by lung epithelial cells		JOURNAL OF IMMUNOLOGY		GROUP-III ALLERGEN; DERMATOPHAGOIDES-PTERONYSSINUS; AIRWAY HYPERRESPONSIVENESS; THROMBIN RECEPTORS; GENE-EXPRESSION; ATOPIC ASTHMA; RELEASE; CLONING; KERATINOCYTES; INFLAMMATION	The respiratory epithelium represents the first barrier encountered by airborne Ags. Two major dust mite Ags, Der p3 and Der p9, are serine proteases that may activate lung epithelial cells by interaction with the protease-activated receptor 2 (PAR-2). In this study both Der p3 and Der p9 cleaved the peptide corresponding to the N terminus of PAR-2 at the activation site. Both Ags sequentially stimulated phosphoinositide hydrolysis, transient cytosolic Ca2+ mobilization, and release of GM-CSF and eotaxin in human pulmonary epithelial cells. These responses were similar to those observed with trypsin and a specific PAR-2 agonist and were related to the serine protease activity of Der p3 and Der p9. Cell exposure to the Ags resulted in a refractory period, indicating that a PAR had been cleaved. Partial desensitization to Der p3 and Der p9 by the PAR-2 agonist suggested that PAR-2 was one target of the Ags. However, PAR-2 was not the only target, because the PAR-2 agonist caused less desensitization to Der p3 and Der p9 than did trypsin. A phospholipase C inhibitor prevented the cytokine-releasing effect of the PAR-2 agonist and abolished or reduced (> 70%) the cytokine-releasing effects of Der p3 and Der p9. Our results suggest that Der p 3 and Der p9 may induce a nonallergic inflammatory response in the airways through the release of proinflammatory cytokines from the bronchial epithelium and that this effect is at least in part mediated by PAR-2.	47	213	2001	8		Immunology
Association of lower continuity of care with greater risk of emergency department use and hospitalization in children. Context. The benefits of continuity of pediatric care remain controversial. Objective. To determine whether there is an association between having a continuous relationship with a primary care pediatric provider and decreased risk of emergency department (ED) visitation and hospitalization. Design. Retrospective cohort study. Setting and Population. We used claims data from 46 097 pediatric patients enrolled at Group Health Cooperative, a large staff-model health maintenance organization, between January 1, 1993, and December 31, 1998, for our analysis. To be eligible, patients had to have been continuously enrolled for at least a 2-year period or since birth and to have made at least 4 visits to one of the Group Health Cooperative clinics. Main Exposure Variable. A continuity of care (COC) index that quantifies the degree to which a patient has experienced continuous care with a provider. Main Outcome Measures. ED utilization and hospitalization. Results. Compared with children with the highest COC, children with medium continuity were more likely to have visited the ED (hazard ratio [HR]: 1.28 [1.20-1.36]) and more likely to be hospitalized (HR: 1.22 [1.09-1.38]). Children with the lowest COC were even more likely to have visited the ED (HR: 1.58 [1.49-1.66]) and to be hospitalized (HR: 1.54 [1.33-1.75]). These risks were even greater for children on Medicaid and those with asthma. Conclusions. Lower continuity of primary care is associated with higher risk of ED utilization and hospitalization. Efforts to improve and maintain continuity may be warranted.. continuity of patient care| pediatrics| ambulatory care| emergency department| hospitalization|health-care| services| experience| severity| choice| asthma.	MAR-2001	continuity of patient care| pediatrics| ambulatory care| emergency department| hospitalization|health-care| services| experience| severity| choice| asthma	Christakis, DA; Mell, L; Koepsell, TD; Zimmerman, FJ; Connell, FA	Association of lower continuity of care with greater risk of emergency department use and hospitalization in children		PEDIATRICS	continuity of patient care; pediatrics; ambulatory care; emergency department; hospitalization	HEALTH-CARE; SERVICES; EXPERIENCE; SEVERITY; CHOICE; ASTHMA	Context. The benefits of continuity of pediatric care remain controversial. Objective. To determine whether there is an association between having a continuous relationship with a primary care pediatric provider and decreased risk of emergency department (ED) visitation and hospitalization. Design. Retrospective cohort study. Setting and Population. We used claims data from 46 097 pediatric patients enrolled at Group Health Cooperative, a large staff-model health maintenance organization, between January 1, 1993, and December 31, 1998, for our analysis. To be eligible, patients had to have been continuously enrolled for at least a 2-year period or since birth and to have made at least 4 visits to one of the Group Health Cooperative clinics. Main Exposure Variable. A continuity of care (COC) index that quantifies the degree to which a patient has experienced continuous care with a provider. Main Outcome Measures. ED utilization and hospitalization. Results. Compared with children with the highest COC, children with medium continuity were more likely to have visited the ED (hazard ratio [HR]: 1.28 [1.20-1.36]) and more likely to be hospitalized (HR: 1.22 [1.09-1.38]). Children with the lowest COC were even more likely to have visited the ED (HR: 1.58 [1.49-1.66]) and to be hospitalized (HR: 1.54 [1.33-1.75]). These risks were even greater for children on Medicaid and those with asthma. Conclusions. Lower continuity of primary care is associated with higher risk of ED utilization and hospitalization. Efforts to improve and maintain continuity may be warranted.	40	213	2001	6	10.1542/peds.107.3.524	Pediatrics
Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march. Background: Childhood eczema often precedes the development of asthma and allergic rhinitis in the so-called atopic march. Recently, 2 loss-of-function mutations in the gene encoding the epidermal barrier protein filaggrin were reported to be predisposing factors for eczema and concomitant asthma, suggesting a possible role in disease transition. Objective: We aimed to assess the importance of filaggrin loss-of-function mutations in the susceptibility to eczema and associated clinical phenotypes. Methods: The filaggrin mutations were genotyped and tested for association with allergic disorders in 2 large European populations including 1092 children with eczema. Results: Highly significant association of the filaggrin null mutations with eczema and concomitant asthma was replicated. Moreover, we found that these mutations predispose to asthma, allergic rhinitis, and allergic sensitization only in the presence of eczema. We show that the presence of 2 filaggrin null alleles is an independent risk factor for asthma in children with eczema, and that the 2 investigated mutations account for about 11% of eczema cases in the German population. Conclusion: These results lend strong support to the role of filaggrin in the pathogenesis of eczema and in the subsequent progression along the atopic march. The fact that previous expression of eczema is a prerequisite for the manifestation of allergic airways disease and specific sensitization highlights the importance of the epidermal barrier in the pathogenesis of these disorders. Clinical implications: Our results suggest that the maintenance and repair of the epidermal barrier in infants with eczema may prevent the subsequent development of allergic airways disease.. eczema| atopic march| asthma| allergic rhinitis| atopy| filaggrin| genetic association| skin barrier|cornified envelope| dermatitis| asthma| skin| association| protein| sensitization| exposure| linkage| mice.	OCT-2006	eczema| atopic march| asthma| allergic rhinitis| atopy| filaggrin| genetic association| skin barrier|cornified envelope| dermatitis| asthma| skin| association| protein| sensitization| exposure| linkage| mice	Marenholz, I; Nickel, R; Ruschendorf, F; Schulz, F; Esparza-Gordillo, J; Kerscher, T; Gruber, C; Lau, S; Worm, M; Keil, T; Kurek, M; Zaluga, E; Wahn, U; Lee, YA	Filaggrin loss-of-function mutations predispose to phenotypes involved in the atopic march		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	eczema; atopic march; asthma; allergic rhinitis; atopy; filaggrin; genetic association; skin barrier	CORNIFIED ENVELOPE; DERMATITIS; ASTHMA; SKIN; ASSOCIATION; PROTEIN; SENSITIZATION; EXPOSURE; LINKAGE; MICE	Background: Childhood eczema often precedes the development of asthma and allergic rhinitis in the so-called atopic march. Recently, 2 loss-of-function mutations in the gene encoding the epidermal barrier protein filaggrin were reported to be predisposing factors for eczema and concomitant asthma, suggesting a possible role in disease transition. Objective: We aimed to assess the importance of filaggrin loss-of-function mutations in the susceptibility to eczema and associated clinical phenotypes. Methods: The filaggrin mutations were genotyped and tested for association with allergic disorders in 2 large European populations including 1092 children with eczema. Results: Highly significant association of the filaggrin null mutations with eczema and concomitant asthma was replicated. Moreover, we found that these mutations predispose to asthma, allergic rhinitis, and allergic sensitization only in the presence of eczema. We show that the presence of 2 filaggrin null alleles is an independent risk factor for asthma in children with eczema, and that the 2 investigated mutations account for about 11% of eczema cases in the German population. Conclusion: These results lend strong support to the role of filaggrin in the pathogenesis of eczema and in the subsequent progression along the atopic march. The fact that previous expression of eczema is a prerequisite for the manifestation of allergic airways disease and specific sensitization highlights the importance of the epidermal barrier in the pathogenesis of these disorders. Clinical implications: Our results suggest that the maintenance and repair of the epidermal barrier in infants with eczema may prevent the subsequent development of allergic airways disease.	27	211	2006	6	10.1016/j.jaci.2006.07.026	Allergy; Immunology
Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials. Objective: To evaluate the efficacy of sublingual immunotherapy (SLIT) in the treatment of allergic rhinitis in children. Data Sources: A comprehensive search of the EMBASE, MEDLINE, LILACS, and CINAHL databases from January 1966 to February 10, 2006, was performed. Study Selection: Randomized, double-blind, placebo-controlled trials of SLIT in the treatment of allergic rhinitis in patients 18 years or younger were selected. Outcomes measured were symptom scores and rescue medication use. Analysis was performed with standardized mean differences (SMDs) and a random-effects model. Results: Seventy articles were identified and reviewed. Ten studies, published between 1990 and 2004, fulfilled the selection criteria. Five hundred seventy-seven patients were initially included in the studies. Of these patients, 484 (245 SLIT and 239 placebo) had a final clinical evaluation and could be evaluated. A relevant heterogeneity due to widely differing scoring systems was found. Overall, there was a significant reduction in both symptoms (SMD, 0.56, 95% confidence interval, 1.01-0.10; P = .02) and medication use (SMD, 0.76; 95% confidence interval, 1.46-0.06; P = .03) after immunotherapy. The subanalyses performed for treatment duration and type of allergen showed that SLIT for more than 18 months and with pollen extracts was effective compared with SLIT courses shorter than 18 months and with mites. Conclusion: The results of this meta-analysis showed that, compared with placebo, SLIT with standardized extracts is effective in pediatric patients with allergic rhinitis.. house-dust mite| swallow immunotherapy| grass-pollen| clinical-efficacy| children| safety| asthma| rhinoconjunctivitis| quality| extract.	AUG-2006	house-dust mite| swallow immunotherapy| grass-pollen| clinical-efficacy| children| safety| asthma| rhinoconjunctivitis| quality| extract	Penagos, M; Compalati, E; Tarantini, F; Baena-Cagnani, R; Huerta, J; Passalacqua, G; Canonica, GW	Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		HOUSE-DUST MITE; SWALLOW IMMUNOTHERAPY; GRASS-POLLEN; CLINICAL-EFFICACY; CHILDREN; SAFETY; ASTHMA; RHINOCONJUNCTIVITIS; QUALITY; EXTRACT	Objective: To evaluate the efficacy of sublingual immunotherapy (SLIT) in the treatment of allergic rhinitis in children. Data Sources: A comprehensive search of the EMBASE, MEDLINE, LILACS, and CINAHL databases from January 1966 to February 10, 2006, was performed. Study Selection: Randomized, double-blind, placebo-controlled trials of SLIT in the treatment of allergic rhinitis in patients 18 years or younger were selected. Outcomes measured were symptom scores and rescue medication use. Analysis was performed with standardized mean differences (SMDs) and a random-effects model. Results: Seventy articles were identified and reviewed. Ten studies, published between 1990 and 2004, fulfilled the selection criteria. Five hundred seventy-seven patients were initially included in the studies. Of these patients, 484 (245 SLIT and 239 placebo) had a final clinical evaluation and could be evaluated. A relevant heterogeneity due to widely differing scoring systems was found. Overall, there was a significant reduction in both symptoms (SMD, 0.56, 95% confidence interval, 1.01-0.10; P = .02) and medication use (SMD, 0.76; 95% confidence interval, 1.46-0.06; P = .03) after immunotherapy. The subanalyses performed for treatment duration and type of allergen showed that SLIT for more than 18 months and with pollen extracts was effective compared with SLIT courses shorter than 18 months and with mites. Conclusion: The results of this meta-analysis showed that, compared with placebo, SLIT with standardized extracts is effective in pediatric patients with allergic rhinitis.	48	211	2006	8		Allergy; Immunology
Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. Background: Specific immunotherapy is widely used to treat allergic rhinitis, but few large-scale clinical trials have been performed. Objective: We sought to assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with standard drug therapy. Methods: We performed a double-blind, randomized, placebo-controlled study of 410 subjects (203 randomized to 100,000 standardized quality units [SQ-U] maintenance, 104 to 10,000 SQ-U, and 103 to placebo). Three hundred forty-seven (85%) completed treatment. Groups were well matched for demographics and symptoms. Results: Across the whole pollen season, mean symptom and medication scores were 29% and 32% lower, respectively, in the 100,000-SQ-U group compared with those in the placebo group (both P < .001). Over the peak pollen season, mean symptom and medication scores were 32% and 41% lower, respectively, than those in the placebo group. The 10,000-SQ-U group had 22% less symptoms than the placebo group over the whole season (P < .01), but medication scores reduced by only 16% (P = .16). Quality-of-life measures confirmed the superiority of both doses to placebo. Local and delayed side effects were common but generally mild. Clinically significant early and delayed systemic side effects were confined to the 100,000-SQ-U group, but no life-threatening reactions occurred. Conclusions: One season of immunotherapy with Alutard grass pollen reduced symptoms and medication use and improved the quality of life of subjects with moderately severe hay fever. The 100,000-SQ-U regimen was more effective, but the 10,000-SQ-U regimen caused fewer side effects.. immunotherapy| allergic rhinitis| efficacy| safety| quality of life| grass pollen|grass-pollen immunotherapy| house-dust-mite| clinical-efficacy| general-practice| position paper| hay-fever| sensitizations| rhinitis| children| asthma.	FEB-2006	immunotherapy| allergic rhinitis| efficacy| safety| quality of life| grass pollen|grass-pollen immunotherapy| house-dust-mite| clinical-efficacy| general-practice| position paper| hay-fever| sensitizations| rhinitis| children| asthma	Frew, AJ; Powell, RJ; Corrigan, CJ; Durham, SR	Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	immunotherapy; allergic rhinitis; efficacy; safety; quality of life; grass pollen	GRASS-POLLEN IMMUNOTHERAPY; HOUSE-DUST-MITE; CLINICAL-EFFICACY; GENERAL-PRACTICE; POSITION PAPER; HAY-FEVER; SENSITIZATIONS; RHINITIS; CHILDREN; ASTHMA	Background: Specific immunotherapy is widely used to treat allergic rhinitis, but few large-scale clinical trials have been performed. Objective: We sought to assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with standard drug therapy. Methods: We performed a double-blind, randomized, placebo-controlled study of 410 subjects (203 randomized to 100,000 standardized quality units [SQ-U] maintenance, 104 to 10,000 SQ-U, and 103 to placebo). Three hundred forty-seven (85%) completed treatment. Groups were well matched for demographics and symptoms. Results: Across the whole pollen season, mean symptom and medication scores were 29% and 32% lower, respectively, in the 100,000-SQ-U group compared with those in the placebo group (both P < .001). Over the peak pollen season, mean symptom and medication scores were 32% and 41% lower, respectively, than those in the placebo group. The 10,000-SQ-U group had 22% less symptoms than the placebo group over the whole season (P < .01), but medication scores reduced by only 16% (P = .16). Quality-of-life measures confirmed the superiority of both doses to placebo. Local and delayed side effects were common but generally mild. Clinically significant early and delayed systemic side effects were confined to the 100,000-SQ-U group, but no life-threatening reactions occurred. Conclusions: One season of immunotherapy with Alutard grass pollen reduced symptoms and medication use and improved the quality of life of subjects with moderately severe hay fever. The 100,000-SQ-U regimen was more effective, but the 10,000-SQ-U regimen caused fewer side effects.	17	210	2006	7	10.1016/j.jaci.2005.11.014	Allergy; Immunology
House dust mite allergens induce proinflammatory cytokines from respiratory epithelial cells: The cysteine protease allergen, Der p 1, activates protease-activated receptor (PAR)-2 and inactivates PAR-1. In previous studies, we demonstrated that allergenic house dust mite proteases are potent inducers of proinflammatory cytokines from the respiratory epithelium, although the precise mechanisms involved were unclear. In this study, we investigated whether this was achieved through activation of protease-activated receptor (PAR)-1 or -2. Pretreatment of A549 respiratory epithelial cells with the clinically important cysteine protease allergen, Der p 1, ablated subsequent PAR-1, but not PAR-2 agonist peptide-induced IL-6 and IL-8 release. HeLa cells transfected with the plasmid coding for PAR-2, in contrast to PAR-1, released significant concentration of IL-6 after exposure to Der p 1. Exposure of HeLa cells transfected with either PAR-1/enhanced yellow fusion protein or PAR-2/enhanced yellow fusion protein to Der p 1 caused receptor internalization in the latter cells only, as judged by confocal microscopy with re-expression of the receptor within 120-min postenzyme exposure. Der p 1-induced cytokine release from both A549 and transfected HeLa cells was accompanied by changes in intracellular C2+ concentrations. Desensitization studies showed that Der p 1 pretreatment of the A549 cells resulted in the abolition of both trypsin- and PAR-2 agonist peptide-induced Ca2+ release, but not that induced by subsequent exposure to either thrombin or PAR-1 agonist peptide. These data indicate for the first time that the house dust mite allergen Der p 1-induced cytokine release from respiratory epithelial cells is, in part, mediated by activation of PAR-2, but not PAR-1.. thrombin receptor| dermatophagoides-pteronyssinus| bronchial epithelium| airway inflammation| tight junctions| cathepsin-g| asthma| cleavage| interleukin-8| permeability.	OCT 15-2002	thrombin receptor| dermatophagoides-pteronyssinus| bronchial epithelium| airway inflammation| tight junctions| cathepsin-g| asthma| cleavage| interleukin-8| permeability	Asokananthan, N; Graham, PT; Stewart, DJ; Bakker, AJ; Eidne, KA; Thompson, PJ; Stewart, GA	House dust mite allergens induce proinflammatory cytokines from respiratory epithelial cells: The cysteine protease allergen, Der p 1, activates protease-activated receptor (PAR)-2 and inactivates PAR-1		JOURNAL OF IMMUNOLOGY		THROMBIN RECEPTOR; DERMATOPHAGOIDES-PTERONYSSINUS; BRONCHIAL EPITHELIUM; AIRWAY INFLAMMATION; TIGHT JUNCTIONS; CATHEPSIN-G; ASTHMA; CLEAVAGE; INTERLEUKIN-8; PERMEABILITY	In previous studies, we demonstrated that allergenic house dust mite proteases are potent inducers of proinflammatory cytokines from the respiratory epithelium, although the precise mechanisms involved were unclear. In this study, we investigated whether this was achieved through activation of protease-activated receptor (PAR)-1 or -2. Pretreatment of A549 respiratory epithelial cells with the clinically important cysteine protease allergen, Der p 1, ablated subsequent PAR-1, but not PAR-2 agonist peptide-induced IL-6 and IL-8 release. HeLa cells transfected with the plasmid coding for PAR-2, in contrast to PAR-1, released significant concentration of IL-6 after exposure to Der p 1. Exposure of HeLa cells transfected with either PAR-1/enhanced yellow fusion protein or PAR-2/enhanced yellow fusion protein to Der p 1 caused receptor internalization in the latter cells only, as judged by confocal microscopy with re-expression of the receptor within 120-min postenzyme exposure. Der p 1-induced cytokine release from both A549 and transfected HeLa cells was accompanied by changes in intracellular C2+ concentrations. Desensitization studies showed that Der p 1 pretreatment of the A549 cells resulted in the abolition of both trypsin- and PAR-2 agonist peptide-induced Ca2+ release, but not that induced by subsequent exposure to either thrombin or PAR-1 agonist peptide. These data indicate for the first time that the house dust mite allergen Der p 1-induced cytokine release from respiratory epithelial cells is, in part, mediated by activation of PAR-2, but not PAR-1.	48	210	2002	7		Immunology
National burden of disease in India from indoor air pollution. In the last decade, a number of quantitative epidemiological studies of specific diseases have been done in developing countries that for the first time allow estimation of the total burden of disease (mortality and morbidity) attributable to use of solid fuels in adult women and young children, who jointly receive the highest exposures because of their household roles. Few such studies are available as yet for adult men or children over 5 years. This paper evaluates the existing epidemiological studies and applies the resulting risks to the more than three-quarters of all Indian households dependent on such fuels. Allowance is made for the existence of improved stoves with chimneys and other factors that may lower exposures. Attributable risks are calculated in reference to the demographic conditions and patterns of each disease in India. Sufficient evidence is available to estimate risks most confidently for acute respiratory infections (ARI), chronic obstructive pulmonary disease (COPD), and lung cancer, Estimates for tuberculosis (TB), asthma, and blindness are of intermediate confidence. Estimates for heart disease have the lowest confidence. Insufficient quantitative evidence is currently available to estimate the impact of adverse pregnancy outcomes (e.g., low birthweight and stillbirth). The resulting conservative estimates indicate that some 400-550 thousand premature deaths can be attributed annually to use of biomass fuels in these population groups. Using a disability-adjusted lost life-year approach, the total is 4-6% of the Indian national burden of disease, placing indoor air pollution as a major risk factor in the country.. environmental tobacco-smoke| lower respiratory-infections| biomass fuel combustion| young gambian children| wood-burning stoves| low-birth-weight| risk-factors| developing-countries| united-states| chronic-bronchitis.	NOV 21-2000	environmental tobacco-smoke| lower respiratory-infections| biomass fuel combustion| young gambian children| wood-burning stoves| low-birth-weight| risk-factors| developing-countries| united-states| chronic-bronchitis	Smith, KR	National burden of disease in India from indoor air pollution		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA		ENVIRONMENTAL TOBACCO-SMOKE; LOWER RESPIRATORY-INFECTIONS; BIOMASS FUEL COMBUSTION; YOUNG GAMBIAN CHILDREN; WOOD-BURNING STOVES; LOW-BIRTH-WEIGHT; RISK-FACTORS; DEVELOPING-COUNTRIES; UNITED-STATES; CHRONIC-BRONCHITIS	In the last decade, a number of quantitative epidemiological studies of specific diseases have been done in developing countries that for the first time allow estimation of the total burden of disease (mortality and morbidity) attributable to use of solid fuels in adult women and young children, who jointly receive the highest exposures because of their household roles. Few such studies are available as yet for adult men or children over 5 years. This paper evaluates the existing epidemiological studies and applies the resulting risks to the more than three-quarters of all Indian households dependent on such fuels. Allowance is made for the existence of improved stoves with chimneys and other factors that may lower exposures. Attributable risks are calculated in reference to the demographic conditions and patterns of each disease in India. Sufficient evidence is available to estimate risks most confidently for acute respiratory infections (ARI), chronic obstructive pulmonary disease (COPD), and lung cancer, Estimates for tuberculosis (TB), asthma, and blindness are of intermediate confidence. Estimates for heart disease have the lowest confidence. Insufficient quantitative evidence is currently available to estimate the impact of adverse pregnancy outcomes (e.g., low birthweight and stillbirth). The resulting conservative estimates indicate that some 400-550 thousand premature deaths can be attributed annually to use of biomass fuels in these population groups. Using a disability-adjusted lost life-year approach, the total is 4-6% of the Indian national burden of disease, placing indoor air pollution as a major risk factor in the country.	133	210	2000	8	10.1073/pnas.97.24.13286	Science & Technology - Other Topics
Health effects of particles in ambient air. A summary of a critical review by a working group of the German commission on Air Pollution Prevention of VDI and DIN of the actual data on exposure and health effects (excluding cancer) of fine particulate air pollution is presented. Exposure: Typical ambient particle concentrations for PM10 (PM2.5) in Germany are in the range of 10-45 (10-30) mug/m(3) as annual mean and 50-200 (40-150) mug/m(3) as maximum daily mean. The ratio Of PM2.5/PM10 generally amounts between 0.7 and 0.9. Health effects: During the past 10 years many new epidemiological and toxicological studies on health effects of particulate matter (PM) have been published. In summary, long-term exposure against PM for years or decades is associated with elevated total, cardiovascular, and infant mortality. With respect to morbidity, respiratory symptoms, lung growth, and function of the immune system are affected. Short-term studies show consistant associations of exposure to daily concentrations of PM with mortality and morbidity on the same day or the subsequent days. Patients with asthma, COPD, pneumonia, and other respiratory diseases as well as patients with cardio-vascular diseases and diabetes are especially affected. The strongest associations are found for PM2.5 followed by PM10, with no indication of a threshold value for the health effects. The data base for ultra fine particles is too small for final conclusions.. particulate matter| air pollution| pm10| pm2.5| ultra fine particles| health effects| review| limit values|long-term exposure| oil fly-ash| north-american children| respiratory symptoms| infant-mortality| inflammatory responses| particulate matter| human volunteers| united-states| acid aerosols.	SEP-2004	particulate matter| air pollution| pm10| pm2.5| ultra fine particles| health effects| review| limit values|long-term exposure| oil fly-ash| north-american children| respiratory symptoms| infant-mortality| inflammatory responses| particulate matter| human volunteers| united-states| acid aerosols	Kappos, AD; Bruckmann, P; Eikmann, T; Englert, N; Heinrich, U; Hoppe, P; Koch, E; Krause, GHM; Kreyling, WG; Rauchfuss, K; Rombout, P; Schulz-Klemp, V; Thiel, WR; Wichmann, HE	Health effects of particles in ambient air		INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH	particulate matter; air pollution; PM10; PM2.5; ultra fine particles; health effects; review; limit values	LONG-TERM EXPOSURE; OIL FLY-ASH; NORTH-AMERICAN CHILDREN; RESPIRATORY SYMPTOMS; INFANT-MORTALITY; INFLAMMATORY RESPONSES; PARTICULATE MATTER; HUMAN VOLUNTEERS; UNITED-STATES; ACID AEROSOLS	A summary of a critical review by a working group of the German commission on Air Pollution Prevention of VDI and DIN of the actual data on exposure and health effects (excluding cancer) of fine particulate air pollution is presented. Exposure: Typical ambient particle concentrations for PM10 (PM2.5) in Germany are in the range of 10-45 (10-30) mug/m(3) as annual mean and 50-200 (40-150) mug/m(3) as maximum daily mean. The ratio Of PM2.5/PM10 generally amounts between 0.7 and 0.9. Health effects: During the past 10 years many new epidemiological and toxicological studies on health effects of particulate matter (PM) have been published. In summary, long-term exposure against PM for years or decades is associated with elevated total, cardiovascular, and infant mortality. With respect to morbidity, respiratory symptoms, lung growth, and function of the immune system are affected. Short-term studies show consistant associations of exposure to daily concentrations of PM with mortality and morbidity on the same day or the subsequent days. Patients with asthma, COPD, pneumonia, and other respiratory diseases as well as patients with cardio-vascular diseases and diabetes are especially affected. The strongest associations are found for PM2.5 followed by PM10, with no indication of a threshold value for the health effects. The data base for ultra fine particles is too small for final conclusions.	65	209	2004	9	10.1078/1438-4639-00306	Public, Environmental & Occupational Health; Infectious Diseases
Respiratory and Allergic Health Effects of Dampness, Mold, and Dampness-Related Agents: A Review of the Epidemiologic Evidence. OBJECTIVES: Many studies have shown consistent associations between evident indoor dampness or mold and respiratory or allergic health effects, but causal links remain unclear. Findings on measured microbiologic factors have received little review. We conducted an updated, comprehensive review on these topics. DATA SOURCES: We reviewed eligible peer-reviewed epidemiologic studies or quantitative meta-analyses, up to late 2009, on dampness, mold, or other microbiologic agents and respiratory or allergic effects. DATA EXTRACTION: We evaluated evidence for causation or association between qualitative/subjective assessments of dampness or mold (considered together) and specific health outcomes. We separately considered evidence for associations between specific quantitative measurements of microbiologic factors and each health outcome. DATA SYNTHESIS: Evidence from epidemiologic studies and meta-analyses showed indoor dampness or mold to be associated consistently with increased asthma development and exacerbation, current and ever diagnosis of asthma, dyspnea, wheeze, cough, respiratory infections, bronchitis, allergic rhinitis, eczema, and upper respiratory tract symptoms. Associations were found in allergic and nonallergic individuals. Evidence strongly suggested causation of asthma exacerbation in children. Suggestive evidence was available for only a few specific measured microbiologic factors and was in part equivocal, suggesting both adverse and protective associations with health. CONCLUSIONS: Evident dampness or mold had consistent positive associations with multiple allergic and respiratory effects. Measured microbiologic agents in dust had limited suggestive associations, including both positive and negative associations for some agents. Thus, prevention and remediation of indoor dampness and mold are likely to reduce health risks, but current evidence does not support measuring specific indoor microbiologic factors to guide health-protective actions.. allergy| asthma| dampness| fungi| indoor air| moisture| mold|house-dust endotoxin| environmental risk-factors| incident case-control| adult-onset asthma| birth-cohort| childhood asthma| indoor mold| hypersensitivity pneumonitis| bronchial obstruction| scientific evidence.	JUN-2011	allergy| asthma| dampness| fungi| indoor air| moisture| mold|house-dust endotoxin| environmental risk-factors| incident case-control| adult-onset asthma| birth-cohort| childhood asthma| indoor mold| hypersensitivity pneumonitis| bronchial obstruction| scientific evidence	Mendell, MJ; Mirer, AG; Cheung, K; Tong, M; Douwes, J	Respiratory and Allergic Health Effects of Dampness, Mold, and Dampness-Related Agents: A Review of the Epidemiologic Evidence		ENVIRONMENTAL HEALTH PERSPECTIVES	allergy; asthma; dampness; fungi; indoor air; moisture; mold	HOUSE-DUST ENDOTOXIN; ENVIRONMENTAL RISK-FACTORS; INCIDENT CASE-CONTROL; ADULT-ONSET ASTHMA; BIRTH-COHORT; CHILDHOOD ASTHMA; INDOOR MOLD; HYPERSENSITIVITY PNEUMONITIS; BRONCHIAL OBSTRUCTION; SCIENTIFIC EVIDENCE	OBJECTIVES: Many studies have shown consistent associations between evident indoor dampness or mold and respiratory or allergic health effects, but causal links remain unclear. Findings on measured microbiologic factors have received little review. We conducted an updated, comprehensive review on these topics. DATA SOURCES: We reviewed eligible peer-reviewed epidemiologic studies or quantitative meta-analyses, up to late 2009, on dampness, mold, or other microbiologic agents and respiratory or allergic effects. DATA EXTRACTION: We evaluated evidence for causation or association between qualitative/subjective assessments of dampness or mold (considered together) and specific health outcomes. We separately considered evidence for associations between specific quantitative measurements of microbiologic factors and each health outcome. DATA SYNTHESIS: Evidence from epidemiologic studies and meta-analyses showed indoor dampness or mold to be associated consistently with increased asthma development and exacerbation, current and ever diagnosis of asthma, dyspnea, wheeze, cough, respiratory infections, bronchitis, allergic rhinitis, eczema, and upper respiratory tract symptoms. Associations were found in allergic and nonallergic individuals. Evidence strongly suggested causation of asthma exacerbation in children. Suggestive evidence was available for only a few specific measured microbiologic factors and was in part equivocal, suggesting both adverse and protective associations with health. CONCLUSIONS: Evident dampness or mold had consistent positive associations with multiple allergic and respiratory effects. Measured microbiologic agents in dust had limited suggestive associations, including both positive and negative associations for some agents. Thus, prevention and remediation of indoor dampness and mold are likely to reduce health risks, but current evidence does not support measuring specific indoor microbiologic factors to guide health-protective actions.	74	208	2011	9	10.1289/ehp.1002410	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Effect of Bronchoconstriction on Airway Remodeling in Asthma. BACKGROUND Asthma is characterized pathologically by structural changes in the airway, termed airway remodeling. These changes are associated with worse long-term clinical outcomes and have been attributed to eosinophilic inflammation. In vitro studies indicate, however, that the compressive mechanical forces that arise during broncho-constriction may induce remodeling independently of inflammation. We evaluated the influence of repeated experimentally induced bronchoconstriction on airway structural changes in patients with asthma. METHODS We randomly assigned 48 subjects with asthma to one of four inhalation challenge protocols involving a series of three challenges with one type of inhaled agent presented at 48-hour intervals. The two active challenges were with either a dust-mite allergen (which causes bronchoconstriction and eosinophilic inflammation) or methacholine (which causes bronchoconstriction without eosinophilic inflammation); the two control challenges (neither of which causes bronchoconstriction) were either saline alone or albuterol followed by methacholine (to control for non-bronchoconstrictor effects of methacholine). Bronchial-biopsy specimens were obtained before and 4 days after completion of the challenges. RESULTS Allergen and methacholine immediately induced similar levels of bronchoconstriction. Eosinophilic inflammation of the airways increased only in the allergen group, whereas both the allergen and the methacholine groups had significant airway remodeling not seen in the two control groups. Subepithelial collagen-band thickness increased by a median of 2.17 mu m in the allergen group (interquartile range [IQR], 0.70 to 3.67) and 1.94 mu m in the methacholine group (IQR, 0.37 to 3.24) (P<0.001 for the comparison of the two challenge groups with the two control groups); periodic acid-Schiff staining of epithelium (mucus glands) also increased, by a median of 2.17 percentage points in the allergen group (IQR, 1.03 to 4.77) and 2.13 percentage points in the methacholine group (IQR, 1.14 to 7.96) (P=0.003 for the comparison with controls). There were no significant differences between the allergen and methacholine groups. CONCLUSIONS Bronchoconstriction without additional inflammation induces airway remodeling in patients with asthma. These findings have potential implications for management.. growth-factor receptor| allergen challenge| mechanical-stress| epithelial-cells| model| rat| inflammation| expression| guidelines| children.	MAY 26-2011	growth-factor receptor| allergen challenge| mechanical-stress| epithelial-cells| model| rat| inflammation| expression| guidelines| children	Grainge, CL; Lau, LCK; Ward, JA; Dulay, V; Lahiff, G; Wilson, S; Holgate, S; Davies, DE; Howarth, PH	Effect of Bronchoconstriction on Airway Remodeling in Asthma		NEW ENGLAND JOURNAL OF MEDICINE		GROWTH-FACTOR RECEPTOR; ALLERGEN CHALLENGE; MECHANICAL-STRESS; EPITHELIAL-CELLS; MODEL; RAT; INFLAMMATION; EXPRESSION; GUIDELINES; CHILDREN	BACKGROUND Asthma is characterized pathologically by structural changes in the airway, termed airway remodeling. These changes are associated with worse long-term clinical outcomes and have been attributed to eosinophilic inflammation. In vitro studies indicate, however, that the compressive mechanical forces that arise during broncho-constriction may induce remodeling independently of inflammation. We evaluated the influence of repeated experimentally induced bronchoconstriction on airway structural changes in patients with asthma. METHODS We randomly assigned 48 subjects with asthma to one of four inhalation challenge protocols involving a series of three challenges with one type of inhaled agent presented at 48-hour intervals. The two active challenges were with either a dust-mite allergen (which causes bronchoconstriction and eosinophilic inflammation) or methacholine (which causes bronchoconstriction without eosinophilic inflammation); the two control challenges (neither of which causes bronchoconstriction) were either saline alone or albuterol followed by methacholine (to control for non-bronchoconstrictor effects of methacholine). Bronchial-biopsy specimens were obtained before and 4 days after completion of the challenges. RESULTS Allergen and methacholine immediately induced similar levels of bronchoconstriction. Eosinophilic inflammation of the airways increased only in the allergen group, whereas both the allergen and the methacholine groups had significant airway remodeling not seen in the two control groups. Subepithelial collagen-band thickness increased by a median of 2.17 mu m in the allergen group (interquartile range [IQR], 0.70 to 3.67) and 1.94 mu m in the methacholine group (IQR, 0.37 to 3.24) (P<0.001 for the comparison of the two challenge groups with the two control groups); periodic acid-Schiff staining of epithelium (mucus glands) also increased, by a median of 2.17 percentage points in the allergen group (IQR, 1.03 to 4.77) and 2.13 percentage points in the methacholine group (IQR, 1.14 to 7.96) (P=0.003 for the comparison with controls). There were no significant differences between the allergen and methacholine groups. CONCLUSIONS Bronchoconstriction without additional inflammation induces airway remodeling in patients with asthma. These findings have potential implications for management.	33	208	2011	10		General & Internal Medicine
Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. Background: Viral respiratory tract infections and atopy are associated with attacks of wheezing during childhood. However, information about the relationship between viral infections and atopy among children whose attacks of wheezing lead to hospitalization is unclear. Objective: To evaluate the prevalence of viral respiratory tract pathogens among infants and children hospitalized for wheezing and to analyze the results in relation to the patient's age, atopic characteristics, and season of admission. Methods: This was a case-control study of children (age 2 months to 18 years) admitted for wheezing to the University of Virginia Medical Center over a period of 12 months. Children without wheezing were enrolled as controls. Nasal secretions were evaluated for viral pathogens by using cultures, PCR tests, and antigen detection. Total IgE and specific IgE antibody to common aeroallergens; was measured in serum. Results: Seventy percent of children hospitalized for wheezing before age 3 years (n = 79) were admitted between December and March, whereas 46% of children age 3 to 18 years (n = 54) were hospitalized between September and November. Among children younger than 3 years, viral pathogens were detected in 84% (66/79) of wheezing children and 55% (42/77) of controls (P < .001). Respiratory syncytial virus was the dominant pathogen during the winter months, but rhinovirus was more common during other months. Total serum IgE levels were generally low, and values from wheezing and control subjects overlapped considerably. Among children 3 years and older, 61% (33/54) of subjects admitted for wheezing tested positive for virus (predominantly rhinovirus), compared with 21% (12/ 56) of controls (P < .001). The total serum IgE values among wheezing children (geometric mean, 386 IU/mL; 95% CI, 259573) were substantially elevated compared with those of controls (geometric mean, 38 IU/mL; 95% CI, 26-56; P < .001). A significantly higher percentage of wheezing children compared with controls was sensitized to at least 1 of the inhaled allergens tested: 84% (36/43) compared with 33% (15/45; P < .001). The atopic characteristics of wheezing children who tested positive or negative for virus were similar. Conclusions: Viral infections were the dominant risk factor for wheezing among children hospitalized before 3 years of age. By comparison, a large majority of the wheezing children age 3 to 18 years had striking atopic characteristics that may be critical as a risk factor for hospitalization and an adverse response to viral infections, especially infections caused by rhinovirus.. wheezing| asthma| children| hospitalization| viral respiratory tract infections| rhinovirus| respiratory syncytial virus| influenza| total serum ige| inhaled allergens|respiratory syncytial virus| polymerase-chain-reaction| serum ige| airway responsiveness| inhalant allergens| childhood asthma| grass-pollen| risk-factors| dust mite| exacerbations.	AUG-2004	wheezing| asthma| children| hospitalization| viral respiratory tract infections| rhinovirus| respiratory syncytial virus| influenza| total serum ige| inhaled allergens|respiratory syncytial virus| polymerase-chain-reaction| serum ige| airway responsiveness| inhalant allergens| childhood asthma| grass-pollen| risk-factors| dust mite| exacerbations	Heymann, PW; Carper, HT; Murphy, DD; Platts-Mills, TAE; Patrie, J; McLaughlin, AP; Erwin, EA; Shaker, MS; Hellems, M; Peerzada, J; Hayden, FG; Hatley, TK; Chamberlain, R	Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	wheezing; asthma; children; hospitalization; viral respiratory tract infections; rhinovirus; respiratory syncytial virus; influenza; total serum IgE; inhaled allergens	RESPIRATORY SYNCYTIAL VIRUS; POLYMERASE-CHAIN-REACTION; SERUM IGE; AIRWAY RESPONSIVENESS; INHALANT ALLERGENS; CHILDHOOD ASTHMA; GRASS-POLLEN; RISK-FACTORS; DUST MITE; EXACERBATIONS	Background: Viral respiratory tract infections and atopy are associated with attacks of wheezing during childhood. However, information about the relationship between viral infections and atopy among children whose attacks of wheezing lead to hospitalization is unclear. Objective: To evaluate the prevalence of viral respiratory tract pathogens among infants and children hospitalized for wheezing and to analyze the results in relation to the patient's age, atopic characteristics, and season of admission. Methods: This was a case-control study of children (age 2 months to 18 years) admitted for wheezing to the University of Virginia Medical Center over a period of 12 months. Children without wheezing were enrolled as controls. Nasal secretions were evaluated for viral pathogens by using cultures, PCR tests, and antigen detection. Total IgE and specific IgE antibody to common aeroallergens; was measured in serum. Results: Seventy percent of children hospitalized for wheezing before age 3 years (n = 79) were admitted between December and March, whereas 46% of children age 3 to 18 years (n = 54) were hospitalized between September and November. Among children younger than 3 years, viral pathogens were detected in 84% (66/79) of wheezing children and 55% (42/77) of controls (P < .001). Respiratory syncytial virus was the dominant pathogen during the winter months, but rhinovirus was more common during other months. Total serum IgE levels were generally low, and values from wheezing and control subjects overlapped considerably. Among children 3 years and older, 61% (33/54) of subjects admitted for wheezing tested positive for virus (predominantly rhinovirus), compared with 21% (12/ 56) of controls (P < .001). The total serum IgE values among wheezing children (geometric mean, 386 IU/mL; 95% CI, 259573) were substantially elevated compared with those of controls (geometric mean, 38 IU/mL; 95% CI, 26-56; P < .001). A significantly higher percentage of wheezing children compared with controls was sensitized to at least 1 of the inhaled allergens tested: 84% (36/43) compared with 33% (15/45; P < .001). The atopic characteristics of wheezing children who tested positive or negative for virus were similar. Conclusions: Viral infections were the dominant risk factor for wheezing among children hospitalized before 3 years of age. By comparison, a large majority of the wheezing children age 3 to 18 years had striking atopic characteristics that may be critical as a risk factor for hospitalization and an adverse response to viral infections, especially infections caused by rhinovirus.	43	208	2004	9	10.1016/j.jaci.2004.04.006	Allergy; Immunology
Protection from experimental asthma by an endogenous bronchodilator. Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, witd-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma.. nitric-oxide synthase| protein s-nitrosylation| airway hyperresponsiveness| cystic-fibrosis| nitrogen-oxides| exhaled air| nitrosothiols| disease| inflammation| inhibition.	JUN 10-2005	nitric-oxide synthase| protein s-nitrosylation| airway hyperresponsiveness| cystic-fibrosis| nitrogen-oxides| exhaled air| nitrosothiols| disease| inflammation| inhibition	Que, LG; Liu, LM; Yan, Y; Whitehead, GS; Gavett, SH; Schwartz, DA; Stamler, JS	Protection from experimental asthma by an endogenous bronchodilator		SCIENCE		NITRIC-OXIDE SYNTHASE; PROTEIN S-NITROSYLATION; AIRWAY HYPERRESPONSIVENESS; CYSTIC-FIBROSIS; NITROGEN-OXIDES; EXHALED AIR; NITROSOTHIOLS; DISEASE; INFLAMMATION; INHIBITION	Mechanisms that protect against asthma remain poorly understood. S-nitrosoglutathione (GSNO), an endogenous bronchodilator, is depleted from asthmatic airways, suggesting a protective role. We report that, following allergen challenge, witd-type mice exhibiting airway hyperresponsivity have increased airway levels of the enzyme GSNO reductase (GSNOR) and are depleted of lung S-nitrosothiols (SNOs). In contrast, mice with genetic deletion of GSNOR exhibit increases in lung SNOs and are protected from airway hyperresponsivity. Our results indicate that endogenous SNOs, governed by GSNOR, are critical regulators of airway responsivity and may provide new therapeutic approaches to asthma.	25	207	2005	4	10.1126/science.1108228	Science & Technology - Other Topics
The European Community Respiratory Health Survey II. The European Community Respiratory Health Survey (ECRHS) II will determine the incidence of and risk factors for the development of allergic disease, atopy and rapid loss of lung function in middle-aged adults living in Europe. From 1991-1993, >18,000 individuals took part in ECRHS I and provided information on symptoms and exposure to known or suspected risk factors for asthma. Blood samples for assessment of specific immunoglobulin E to environmental allergen were taken and lung function and bronchial responsiveness to methacholine were assessed. From 1999-2001, study participants were re-contacted to determine symptom status and exposure to a variety of factors, including tobacco smoke, animals, occupational agents and air pollutants (including particulate matter). In a subsample of responders, exposure to house dust-mite allergen was assessed by analysis of dust samples taken from participants' mattresses. In addition, blood samples suitable for deoxyribonucleic acid extraction were collected and stored. Currently, European Community Respiratory Health Survey II is being conducted in 29 centres in 14 countries. At the time of writing this paper, 27 centres had begun the study and similar to12,000 participants had completed a short postal questionnaire, similar to9,000 had completed a more detailed health assessment and 3,500 participants had provided dust samples. Historical air-pollution data have been collated and the programme of monitoring particles with a 50% cut-off aerodynamic diameter of 2.5 mum has been completed in 21 centres in 10 countries.. asthma| atopy| cohort| epidemiology| european community respiratory health survey| forced expiratory volume in one second|party diagnostic-criteria| skin-test reactivity| lung-function| atopic-dermatitis| pulmonary-function| population-sample| aerosol output| air-pollution| asthma| decline.	NOV-2002	asthma| atopy| cohort| epidemiology| european community respiratory health survey| forced expiratory volume in one second|party diagnostic-criteria| skin-test reactivity| lung-function| atopic-dermatitis| pulmonary-function| population-sample| aerosol output| air-pollution| asthma| decline	Jarvis, D	The European Community Respiratory Health Survey II		EUROPEAN RESPIRATORY JOURNAL	asthma; atopy; cohort; epidemiology; European Community Respiratory Health Survey; forced expiratory volume in one second	PARTY DIAGNOSTIC-CRITERIA; SKIN-TEST REACTIVITY; LUNG-FUNCTION; ATOPIC-DERMATITIS; PULMONARY-FUNCTION; POPULATION-SAMPLE; AEROSOL OUTPUT; AIR-POLLUTION; ASTHMA; DECLINE	The European Community Respiratory Health Survey (ECRHS) II will determine the incidence of and risk factors for the development of allergic disease, atopy and rapid loss of lung function in middle-aged adults living in Europe. From 1991-1993, >18,000 individuals took part in ECRHS I and provided information on symptoms and exposure to known or suspected risk factors for asthma. Blood samples for assessment of specific immunoglobulin E to environmental allergen were taken and lung function and bronchial responsiveness to methacholine were assessed. From 1999-2001, study participants were re-contacted to determine symptom status and exposure to a variety of factors, including tobacco smoke, animals, occupational agents and air pollutants (including particulate matter). In a subsample of responders, exposure to house dust-mite allergen was assessed by analysis of dust samples taken from participants' mattresses. In addition, blood samples suitable for deoxyribonucleic acid extraction were collected and stored. Currently, European Community Respiratory Health Survey II is being conducted in 29 centres in 14 countries. At the time of writing this paper, 27 centres had begun the study and similar to12,000 participants had completed a short postal questionnaire, similar to9,000 had completed a more detailed health assessment and 3,500 participants had provided dust samples. Historical air-pollution data have been collated and the programme of monitoring particles with a 50% cut-off aerodynamic diameter of 2.5 mum has been completed in 21 centres in 10 countries.	45	207	2002	9	10.1183/09031936.02.00046802	Respiratory System
Ultrafine particles in urban air and respiratory health among adult asthmatics. Airborne particles are associated with adverse health effects and contribute to excess mortality in epidemiological studies. A recent hypothesis proposes that the high numbers of ultrafine (<0.1 pm diameter) particles in ambient air might provoke alveolar inflammation and subsequently cause exacerbations in pre-existing cardiopulmonary diseases. To test the hypothesis adult asthmatics were followed with daily peak expiratory flow (PEF) measurements and symptom and medication diaries for sis months, while simultaneously monitoring particulate pollution in ambient air. The associations between daily health endpoints of 57 asthmatics and indicators of air pollution mere examined by multivariate regression models. Daily mean number concentration of particles, but not particle mass (PM10 (particle mass < 10 pm), PM2.5-10, PM2.5, PM1), was negatively associated with daily PEF deviations. The strongest effects were seen for particles in the ultrafine range. However, the effect of ultrafine particles could not definitely be separated from other traffic generated pollutants, namely nitric oxide, nitrogen dioxide and carbon monoxide. No associations were observed with respiratory symptoms or medication use. Particle mass measurements can be strongly influenced by mechanically produced, soil-derived particles, which may not be associated with adverse health effects. Therefore, air quality monitoring should include particle number concentrations, which mainly reflect ultrafine particles.. air pollution| asthma| particles| particle size| peak expiratory flow rate| respiratory symptoms|cytokine production| pollution| children| pm10| association| involvement| generation| mortality| exposure| symptoms.	MAR-2001	air pollution| asthma| particles| particle size| peak expiratory flow rate| respiratory symptoms|cytokine production| pollution| children| pm10| association| involvement| generation| mortality| exposure| symptoms	Penttinen, P; Timonen, KL; Tiittanen, P; Mirme, A; Ruuskanen, J; Pekkanen, J	Ultrafine particles in urban air and respiratory health among adult asthmatics		EUROPEAN RESPIRATORY JOURNAL	air pollution; asthma; particles; particle size; peak expiratory flow rate; respiratory symptoms	CYTOKINE PRODUCTION; POLLUTION; CHILDREN; PM10; ASSOCIATION; INVOLVEMENT; GENERATION; MORTALITY; EXPOSURE; SYMPTOMS	Airborne particles are associated with adverse health effects and contribute to excess mortality in epidemiological studies. A recent hypothesis proposes that the high numbers of ultrafine (<0.1 pm diameter) particles in ambient air might provoke alveolar inflammation and subsequently cause exacerbations in pre-existing cardiopulmonary diseases. To test the hypothesis adult asthmatics were followed with daily peak expiratory flow (PEF) measurements and symptom and medication diaries for sis months, while simultaneously monitoring particulate pollution in ambient air. The associations between daily health endpoints of 57 asthmatics and indicators of air pollution mere examined by multivariate regression models. Daily mean number concentration of particles, but not particle mass (PM10 (particle mass < 10 pm), PM2.5-10, PM2.5, PM1), was negatively associated with daily PEF deviations. The strongest effects were seen for particles in the ultrafine range. However, the effect of ultrafine particles could not definitely be separated from other traffic generated pollutants, namely nitric oxide, nitrogen dioxide and carbon monoxide. No associations were observed with respiratory symptoms or medication use. Particle mass measurements can be strongly influenced by mechanically produced, soil-derived particles, which may not be associated with adverse health effects. Therefore, air quality monitoring should include particle number concentrations, which mainly reflect ultrafine particles.	24	207	2001	8	10.1183/09031936.01.17304280	Respiratory System
Antagonism of microRNA-126 suppresses the effector function of T(H)2 cells and the development of allergic airways disease. Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in sensing molecular patterns and in programming adaptive T cell responses. Here we show that in vivo activation of TLR4 by house dust mite antigens leads to the induction of allergic disease, a process that is associated with expression of a unique subset of small, noncoding microRNAs. Selective blockade of microRNA (miR)-126 suppressed the asthmatic phenotype, resulting in diminished T(H)2 responses, inflammation, airways hyperresponsiveness, eosinophil recruitment, and mucus hypersecretion. miR-126 blockade resulted in augmented expression of POU domain class 2 associating factor 1, which activates the transcription factor PU. 1 that alters T(H)2 cell function via negative regulation of GATA3 expression. In summary, this study presents a functional connection between miRNA expression and asthma pathogenesis, and our data suggest that targeting miRNA in the airways may lead to anti-inflammatory treatments for allergic asthma.. animal model| asthma| inflammation| microrna| t(h)2 cytokines|toll-like receptors| dendritic cells| experimental asthma| immune-responses| inhaled antigen| linking innate| plasma-cells| in-vivo| expression| hyperreactivity.	NOV 3-2009	animal model| asthma| inflammation| microrna| t(h)2 cytokines|toll-like receptors| dendritic cells| experimental asthma| immune-responses| inhaled antigen| linking innate| plasma-cells| in-vivo| expression| hyperreactivity	Mattes, J; Collison, A; Plank, M; Phipps, S; Foster, PS	Antagonism of microRNA-126 suppresses the effector function of T(H)2 cells and the development of allergic airways disease		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	animal model; asthma; inflammation; microRNA; T(H)2 cytokines	TOLL-LIKE RECEPTORS; DENDRITIC CELLS; EXPERIMENTAL ASTHMA; IMMUNE-RESPONSES; INHALED ANTIGEN; LINKING INNATE; PLASMA-CELLS; IN-VIVO; EXPRESSION; HYPERREACTIVITY	Allergic asthma is an inflammatory disease of the lung characterized by abnormal T helper-2 (T(H)2) lymphocyte responses to inhaled antigens. The molecular mechanisms leading to the generation of T(H)2 responses remain unclear, although toll-like receptors (TLRs) present on innate immune cells play a pivotal role in sensing molecular patterns and in programming adaptive T cell responses. Here we show that in vivo activation of TLR4 by house dust mite antigens leads to the induction of allergic disease, a process that is associated with expression of a unique subset of small, noncoding microRNAs. Selective blockade of microRNA (miR)-126 suppressed the asthmatic phenotype, resulting in diminished T(H)2 responses, inflammation, airways hyperresponsiveness, eosinophil recruitment, and mucus hypersecretion. miR-126 blockade resulted in augmented expression of POU domain class 2 associating factor 1, which activates the transcription factor PU. 1 that alters T(H)2 cell function via negative regulation of GATA3 expression. In summary, this study presents a functional connection between miRNA expression and asthma pathogenesis, and our data suggest that targeting miRNA in the airways may lead to anti-inflammatory treatments for allergic asthma.	44	206	2009	6	10.1073/pnas.0905063106	Science & Technology - Other Topics
The many faces of the hygiene hypothesis. About 15 years have gone by since Strachan first proposed the idea that infections and unhygienic contact might confer protection against the development of allergic illnesses. The so-called hygiene hypothesis has ever since undergone numerous more or less subtle modifications by various researchers in the fields of epidemiology, clinical science, and immunology. Three major tracts have developed exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and the effect of both on underlying responses of the innate and adaptive immunity. To date, a truly unifying concept has not yet emerged, but various pieces of a complex interplay between immune responses of the host, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures becomes apparent. These influences are discussed as determinants for a number of complex allergic illnesses in this review, while we attempt to pay attention to the importance of different phenotypes, namely of the asthma syndrome. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future.. allergy| asthma| infection| innate| microbial| virus| toll|toll-like receptors| respiratory syncytial virus| regulatory t-cells| killed mycobacterium-vaccae| day-care attendance| bronchial epithelial-cells| early bcg vaccination| school-age-children| hepatitis-a virus| early-life.	MAY-2006	allergy| asthma| infection| innate| microbial| virus| toll|toll-like receptors| respiratory syncytial virus| regulatory t-cells| killed mycobacterium-vaccae| day-care attendance| bronchial epithelial-cells| early bcg vaccination| school-age-children| hepatitis-a virus| early-life	Schaub, B; Lauener, R; von Mutius, E	The many faces of the hygiene hypothesis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; asthma; infection; innate; microbial; virus; toll	TOLL-LIKE RECEPTORS; RESPIRATORY SYNCYTIAL VIRUS; REGULATORY T-CELLS; KILLED MYCOBACTERIUM-VACCAE; DAY-CARE ATTENDANCE; BRONCHIAL EPITHELIAL-CELLS; EARLY BCG VACCINATION; SCHOOL-AGE-CHILDREN; HEPATITIS-A VIRUS; EARLY-LIFE	About 15 years have gone by since Strachan first proposed the idea that infections and unhygienic contact might confer protection against the development of allergic illnesses. The so-called hygiene hypothesis has ever since undergone numerous more or less subtle modifications by various researchers in the fields of epidemiology, clinical science, and immunology. Three major tracts have developed exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and the effect of both on underlying responses of the innate and adaptive immunity. To date, a truly unifying concept has not yet emerged, but various pieces of a complex interplay between immune responses of the host, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures becomes apparent. These influences are discussed as determinants for a number of complex allergic illnesses in this review, while we attempt to pay attention to the importance of different phenotypes, namely of the asthma syndrome. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future.	118	205	2006	9	10.1016/j.jaci.2006.03.003	Allergy; Immunology
Health status deterioration in patients with chronic obstructive pulmonary disease. This study examined health status decline in patients with chronic obstructive pulmonary disease (COPD). Data are from the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. After an 8-wk run-in, 751 patients (566 male), mean age 64 yr, were randomized to receive fluticasone propionate (FP) 500 mug twice daily (376 patients) or placebo (375 patients). Mean baseline postbronchodilator FEV1 was 50 +/- 15% predicted. Patients completed the St George's Respiratory Questionnaire (SGRQ) and the Short-Form 36 (SF-36) at baseline and every 6 mo for 3 yr. FEV1 and smoking status were assessed at baseline and at 3-mo intervals. A total of 387 (212 FP) patients completed the trial. All SGRQ components (p = 0.03 to 0.004) and Physical Function, Mental Health, Energy/Vitality, and Physical Role Limitation scales of the SF-36 (p = 0.05 to 0.005) deteriorated faster in the placebo group. FEV, and SGRQ scores correlated at baseline values (r = -0.25, p < 0.0001), as did change in FEV1 and change in SGRQ (<Delta> r = -0.24, p < 0.0001). At baseline values smokers had worse SGRQ Total, Symptoms, and Impacts scores than ex-smokers. This difference was maintained throughout the study. Smoking status did not influence the rate of decline in health status. The SGRQ Total scores of FP-treated patients took 59% longer than placebo to deteriorate by a clinically significant amount. We conclude that health status decline in moderate to severe COPD can be reduced by high-dose fluticasone.. quality-of-life| george respiratory questionnaire| air-flow limitation| sf-36| asthma| copd.	JAN-2001	quality-of-life| george respiratory questionnaire| air-flow limitation| sf-36| asthma| copd	Spencer, S; Calverley, PMA; Burge, PS; Jones, PW	Health status deterioration in patients with chronic obstructive pulmonary disease		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		QUALITY-OF-LIFE; GEORGE RESPIRATORY QUESTIONNAIRE; AIR-FLOW LIMITATION; SF-36; ASTHMA; COPD	This study examined health status decline in patients with chronic obstructive pulmonary disease (COPD). Data are from the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. After an 8-wk run-in, 751 patients (566 male), mean age 64 yr, were randomized to receive fluticasone propionate (FP) 500 mug twice daily (376 patients) or placebo (375 patients). Mean baseline postbronchodilator FEV1 was 50 +/- 15% predicted. Patients completed the St George's Respiratory Questionnaire (SGRQ) and the Short-Form 36 (SF-36) at baseline and every 6 mo for 3 yr. FEV1 and smoking status were assessed at baseline and at 3-mo intervals. A total of 387 (212 FP) patients completed the trial. All SGRQ components (p = 0.03 to 0.004) and Physical Function, Mental Health, Energy/Vitality, and Physical Role Limitation scales of the SF-36 (p = 0.05 to 0.005) deteriorated faster in the placebo group. FEV, and SGRQ scores correlated at baseline values (r = -0.25, p < 0.0001), as did change in FEV1 and change in SGRQ (<Delta> r = -0.24, p < 0.0001). At baseline values smokers had worse SGRQ Total, Symptoms, and Impacts scores than ex-smokers. This difference was maintained throughout the study. Smoking status did not influence the rate of decline in health status. The SGRQ Total scores of FP-treated patients took 59% longer than placebo to deteriorate by a clinically significant amount. We conclude that health status decline in moderate to severe COPD can be reduced by high-dose fluticasone.	25	205	2001	7		General & Internal Medicine; Respiratory System
Linezolid for Treatment of Chronic Extensively Drug-Resistant Tuberculosis. BACKGROUND Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis. METHODS We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring. RESULTS By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P = 0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed. CONCLUSIONS Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.). intractable multidrug-resistant| mycobacterium-tuberculosis| pulmonary tuberculosis| oxazolidinone antibacterial| murine model| pharmacokinetics| tolerability| moxifloxacin| ofloxacin| efficacy.	OCT 18-2012	intractable multidrug-resistant| mycobacterium-tuberculosis| pulmonary tuberculosis| oxazolidinone antibacterial| murine model| pharmacokinetics| tolerability| moxifloxacin| ofloxacin| efficacy	Lee, M; Lee, J; Carroll, MW; Choi, H; Min, S; Song, T; Via, LE; Goldfeder, LC; Kang, E; Jin, B; Park, H; Kwak, H; Kim, H; Jeon, HS; Jeong, I; Joh, JS; Chen, RY; Olivier, KN; Shaw, PA; Follmann, D; Song, SD; Lee, JK; Lee, D; Kim, CT; Dartois, V; Park, SK; Cho, SN; Barry, CE	Linezolid for Treatment of Chronic Extensively Drug-Resistant Tuberculosis		NEW ENGLAND JOURNAL OF MEDICINE		INTRACTABLE MULTIDRUG-RESISTANT; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; OXAZOLIDINONE ANTIBACTERIAL; MURINE MODEL; PHARMACOKINETICS; TOLERABILITY; MOXIFLOXACIN; OFLOXACIN; EFFICACY	BACKGROUND Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis. METHODS We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring. RESULTS By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P = 0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed. CONCLUSIONS Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.)	45	204	2012	11	10.1056/NEJMoa1201964	General & Internal Medicine
Asthma is associated with weight gain in females but not males, independent of physical activity. We tested whether asthma diagnosis is associated with weight gain and physical activity in 4,547 18 to 30-yr-old African American and white men and women, followed prospectively for up to 10 yr. Baseline asthma was most frequent in African American men. Incident asthma was more frequent in women. Incident asthma was associated with highest and lowest baseline and change in body mass index (BMI), in a J-shaped curve, after adjustment for other factors. When stratified by sex, this association was seen only in females. Subjects on average decreased physical activity and gained weight over time, but there was no significant difference in asthma prevalence by physical activity at baseline or asthma incidence by change in physical activity. Cigarette smoking in females was significantly associated with asthma incidence, but serum cotinine level at baseline among nonsmokers (reflecting environmental tobacco smoke [ETS] exposure) was not significantly associated with asthma. We conclude that gain in BMI predisposes to new asthma diagnosis In female young adults, but decreased physical activity does not explain the association of weight gain with asthma.. asthma| obesity| body mass index| african american| physical activity| epidemiology| environmental tobacco smoke| passive smoking| sex differences|body-mass index| risk| cardia| children| women| men.	DEC 1-2001	asthma| obesity| body mass index| african american| physical activity| epidemiology| environmental tobacco smoke| passive smoking| sex differences|body-mass index| risk| cardia| children| women| men	Beckett, WS; Jacobs, DR; Yu, XH; Iribarren, C; Williams, D	Asthma is associated with weight gain in females but not males, independent of physical activity		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; obesity; body mass index; African American; physical activity; epidemiology; environmental tobacco smoke; passive smoking; sex differences	BODY-MASS INDEX; RISK; CARDIA; CHILDREN; WOMEN; MEN	We tested whether asthma diagnosis is associated with weight gain and physical activity in 4,547 18 to 30-yr-old African American and white men and women, followed prospectively for up to 10 yr. Baseline asthma was most frequent in African American men. Incident asthma was more frequent in women. Incident asthma was associated with highest and lowest baseline and change in body mass index (BMI), in a J-shaped curve, after adjustment for other factors. When stratified by sex, this association was seen only in females. Subjects on average decreased physical activity and gained weight over time, but there was no significant difference in asthma prevalence by physical activity at baseline or asthma incidence by change in physical activity. Cigarette smoking in females was significantly associated with asthma incidence, but serum cotinine level at baseline among nonsmokers (reflecting environmental tobacco smoke [ETS] exposure) was not significantly associated with asthma. We conclude that gain in BMI predisposes to new asthma diagnosis In female young adults, but decreased physical activity does not explain the association of weight gain with asthma.	15	204	2001	6		General & Internal Medicine; Respiratory System
Inhaled corticosteroid use and bone-mineral density in patients with asthma. Background Inhaled corticosteroids are absorbed into the systemic circulation, but the extent to which they have adverse effects on bone is uncertain. The question is important since 3% of the European population take an inhaled corticosteroid regularly and may do so for many years. Methods We studied the dose-response relation between cumulative inhaled corticosteroid dose and bone-mineral density at the lumbar spine and proximal femur in 196 adults (119 women) with asthma aged 20-40 years. Patients had taken an inhaled corticosteroid regularly for at least 6 months, and had had limited exposure to systemic steroids. Cumulative dose of inhaled corticosteroid was calculated from questionnaires and computerised and written general-practice records, and its effect on bone-mineral density was estimated by multiple regression analysis. Findings Median duration of inhaled corticosteroid treatment was 6 years (range 0.5-24), and median cumulative dose was 876 mg (87-4380), There was a negative association between cumulative dose of inhaled corticosteroid and bone-mineral density at the lumbar spine (L2-L4), femoral neck, Ward's triangle, and trochanter, both before and after adjustment for the effects of age and sex. A doubling in dose of inhaled corticosteroid was associated with a decrease in bone-mineral density at the lumbar spine of 0.16 SD (95% CI 0.04-0.28). Similar decreases were found at the femoral neck, Ward's triangle, and trochanter, Adjustment for potential confounding factors including physical activity and past oral, nasal, dermal, and parenteral corticosteroids did not weaken the associations. Interpretation This study provides evidence of a negative relation between total cumulative dose of inhaled corticosteroid and bone-mineral density in patients with asthma.. beclomethasone dipropionate| reference ranges| steroid-therapy| women| risk| budesonide| glucocorticoids| fluticasone| metabolism| fracture.	APR 22-2000	beclomethasone dipropionate| reference ranges| steroid-therapy| women| risk| budesonide| glucocorticoids| fluticasone| metabolism| fracture	Wong, CA; Walsh, LJ; Smith, CJP; Wisniewski, AF; Lewis, SA; Hubbard, R; Cawte, S; Green, DJ; Pringle, M; Tattersfield, AE	Inhaled corticosteroid use and bone-mineral density in patients with asthma		LANCET		BECLOMETHASONE DIPROPIONATE; REFERENCE RANGES; STEROID-THERAPY; WOMEN; RISK; BUDESONIDE; GLUCOCORTICOIDS; FLUTICASONE; METABOLISM; FRACTURE	Background Inhaled corticosteroids are absorbed into the systemic circulation, but the extent to which they have adverse effects on bone is uncertain. The question is important since 3% of the European population take an inhaled corticosteroid regularly and may do so for many years. Methods We studied the dose-response relation between cumulative inhaled corticosteroid dose and bone-mineral density at the lumbar spine and proximal femur in 196 adults (119 women) with asthma aged 20-40 years. Patients had taken an inhaled corticosteroid regularly for at least 6 months, and had had limited exposure to systemic steroids. Cumulative dose of inhaled corticosteroid was calculated from questionnaires and computerised and written general-practice records, and its effect on bone-mineral density was estimated by multiple regression analysis. Findings Median duration of inhaled corticosteroid treatment was 6 years (range 0.5-24), and median cumulative dose was 876 mg (87-4380), There was a negative association between cumulative dose of inhaled corticosteroid and bone-mineral density at the lumbar spine (L2-L4), femoral neck, Ward's triangle, and trochanter, both before and after adjustment for the effects of age and sex. A doubling in dose of inhaled corticosteroid was associated with a decrease in bone-mineral density at the lumbar spine of 0.16 SD (95% CI 0.04-0.28). Similar decreases were found at the femoral neck, Ward's triangle, and trochanter, Adjustment for potential confounding factors including physical activity and past oral, nasal, dermal, and parenteral corticosteroids did not weaken the associations. Interpretation This study provides evidence of a negative relation between total cumulative dose of inhaled corticosteroid and bone-mineral density in patients with asthma.	30	204	2000	5	10.1016/S0140-6736(00)02138-3	General & Internal Medicine
Biology of Lung Dendritic Cells at the Origin of Asthma. Dendritic cells (DCs) initiate and maintain adaptive T helper 2 (Th2) cell responses to inhaled allergens in asthma. Various functions like antigen uptake, migration to the draining LNs, and induction of tolerance and adaptive immunity are not equally shared by all subsets of DCs, adding considerable complexity to understanding the immunology of allergic sensitization. Whereas the epithelium was initially considered solely as a physical barrier, it is now seen as a central player in controlling the function of lung DCs through release of Th2 cell-promoting cytokines. Although DCs are sufficient and necessary for induction of Th2 cell responses to many antigens, some allergens might require antigen presentation by basophils. Clinically relevant allergens, as well as environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells, basophils, and DCs. This review summarizes the recent progress on our understanding how DCs control Th2 cell immunity in the lung.. house-dust mite| allergic airway inflammation| cd4(+) t-cells| respiratory syncytial virus| antigen-presenting cells| blood monocyte subsets| epithelial-cells| immune-responses| inhaled antigen| th2 responses.	SEP 18-2009	house-dust mite| allergic airway inflammation| cd4(+) t-cells| respiratory syncytial virus| antigen-presenting cells| blood monocyte subsets| epithelial-cells| immune-responses| inhaled antigen| th2 responses	Lambrecht, BN; Hammad, H	Biology of Lung Dendritic Cells at the Origin of Asthma		IMMUNITY		HOUSE-DUST MITE; ALLERGIC AIRWAY INFLAMMATION; CD4(+) T-CELLS; RESPIRATORY SYNCYTIAL VIRUS; ANTIGEN-PRESENTING CELLS; BLOOD MONOCYTE SUBSETS; EPITHELIAL-CELLS; IMMUNE-RESPONSES; INHALED ANTIGEN; TH2 RESPONSES	Dendritic cells (DCs) initiate and maintain adaptive T helper 2 (Th2) cell responses to inhaled allergens in asthma. Various functions like antigen uptake, migration to the draining LNs, and induction of tolerance and adaptive immunity are not equally shared by all subsets of DCs, adding considerable complexity to understanding the immunology of allergic sensitization. Whereas the epithelium was initially considered solely as a physical barrier, it is now seen as a central player in controlling the function of lung DCs through release of Th2 cell-promoting cytokines. Although DCs are sufficient and necessary for induction of Th2 cell responses to many antigens, some allergens might require antigen presentation by basophils. Clinically relevant allergens, as well as environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells, basophils, and DCs. This review summarizes the recent progress on our understanding how DCs control Th2 cell immunity in the lung.	121	202	2009	13	10.1016/j.immuni.2009.08.008	Immunology
Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children. The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functions in pathways involved in asthma pathogenesis such as xenobiotic metabolism and antioxidant defenses. Effects of GSTM1 genotype, maternal smoking during pregnancy, and childhood environmental tobacco smoke (ETS) exposure on asthma and wheezing were investigated in 2,950 children enrolled in 4th, 7th, and 10th grade classrooms in 12 Southern California communities. The effects of in utero exposure to maternal smoking on asthma and wheezing occurrence were largely restricted to children with GSTM1 null genotype. Among GSTM1 null children, in utero exposure was associated with increased prevalence of early onset asthma (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.0-2.5), asthma with current symptoms (OR 1.7, 95% Cl 1.1-2.8), persistent asthma (OR 1.6, 95% Cl 1.1-2.4), lifetime history of wheezing (OR 1.8, 95% Cl 1.3-2.5), wheezing with exercise (OR 2.1, 95% Cl 1.3-3.3), wheezing requiring medication (OR 2.2, 95% Cl 1.4-3.4), and emergency room visits in the past year (OR 3.7, 95% Cl 1.9-7.3). Among children with GSTM1 (+) genotype, in utero exposure was not associated with asthma or wheezing. Our findings indicate that there are important long-term effects of in utero exposure in a genetically susceptible group of children.. in utero exposure| tobacco smoke| gstm1| asthma| wheeze| children|parental smoking| childhood asthma| lung-function| oxidative stress| family history| respiratory health| air-pollution| risk-factors| prevalence| exposure.	AUG 15-2002	in utero exposure| tobacco smoke| gstm1| asthma| wheeze| children|parental smoking| childhood asthma| lung-function| oxidative stress| family history| respiratory health| air-pollution| risk-factors| prevalence| exposure	Gilliland, FD; Li, YF; Dubeau, L; Berhane, K; Avol, E; McConnell, R; Gauderman, WJ; Peters, JM	Effects of glutathione S-transferase M1, maternal smoking during pregnancy, and environmental tobacco smoke on asthma and wheezing in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	In utero exposure; tobacco smoke; GSTM1; asthma; wheeze; children	PARENTAL SMOKING; CHILDHOOD ASTHMA; LUNG-FUNCTION; OXIDATIVE STRESS; FAMILY HISTORY; RESPIRATORY HEALTH; AIR-POLLUTION; RISK-FACTORS; PREVALENCE; EXPOSURE	The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functions in pathways involved in asthma pathogenesis such as xenobiotic metabolism and antioxidant defenses. Effects of GSTM1 genotype, maternal smoking during pregnancy, and childhood environmental tobacco smoke (ETS) exposure on asthma and wheezing were investigated in 2,950 children enrolled in 4th, 7th, and 10th grade classrooms in 12 Southern California communities. The effects of in utero exposure to maternal smoking on asthma and wheezing occurrence were largely restricted to children with GSTM1 null genotype. Among GSTM1 null children, in utero exposure was associated with increased prevalence of early onset asthma (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.0-2.5), asthma with current symptoms (OR 1.7, 95% Cl 1.1-2.8), persistent asthma (OR 1.6, 95% Cl 1.1-2.4), lifetime history of wheezing (OR 1.8, 95% Cl 1.3-2.5), wheezing with exercise (OR 2.1, 95% Cl 1.3-3.3), wheezing requiring medication (OR 2.2, 95% Cl 1.4-3.4), and emergency room visits in the past year (OR 3.7, 95% Cl 1.9-7.3). Among children with GSTM1 (+) genotype, in utero exposure was not associated with asthma or wheezing. Our findings indicate that there are important long-term effects of in utero exposure in a genetically susceptible group of children.	54	202	2002	7	10.1164/rccm.2112064	General & Internal Medicine; Respiratory System
Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II). Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study Centre. Findings A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4,1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2,1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.. occupational respiratory-diseases| airways dysfunction syndrome| work-related asthma| reported incidence| epidemiology| surveillance| latex.	JUL-AUG-2007	occupational respiratory-diseases| airways dysfunction syndrome| work-related asthma| reported incidence| epidemiology| surveillance| latex	Kogevinas, M; Zock, JP; Jarvis, D; Kromhout, H; Lillienberg, L; Plana, E; Radon, K; Toren, K; Alliksoo, A; Benke, G; Blanc, PD; Dahlman-Hoglund, A; D'Errico, A; Hery, M; Kennedy, S; Kunzli, N; Leynaert, B; Mirabelli, MC; Muniozguren, N; Norback, D; Olivieri, M; Payo, F; Villani, S; van Sprundel, M; Urrutia, I; Wieslander, G; Sunyer, J; Anto, JM	Exposure to substances in the workplace and new-onset asthma: an international prospective population-based study (ECRHS-II)		LANCET		OCCUPATIONAL RESPIRATORY-DISEASES; AIRWAYS DYSFUNCTION SYNDROME; WORK-RELATED ASTHMA; REPORTED INCIDENCE; EPIDEMIOLOGY; SURVEILLANCE; LATEX	Background The role of exposure to substances in the workplace in new-onset asthma is not well characterised in population-based studies. We therefore aimed to estimate the relative and attributable risks of new-onset asthma in relation to occupations, work-related exposures, and inhalation accidents. Methods We studied prospectively 6837 participants from 13 countries who previously took part in the European Community Respiratory Health Survey (1990-95) and did not report respiratory symptoms or a history of asthma at the time of the first study. Asthma was assessed by methacholine challenge test and by questionnaire data on asthma symptoms. Exposures were defined by high-risk occupations, an asthma-specific job exposure matrix with additional expert judgment, and through self-report of acute inhalation events. Relative risks for new onset asthma were calculated with log-binomial models adjusted for age, sex, smoking, and study Centre. Findings A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (Relative risk=1.6, 95% CI 1.1-2.3, p=0.017). Risks were highest for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4,1.3-4.6, p=0.008). Of common occupations, a significant excess risk of asthma was seen for nursing (2.2,1.3-4.0, p=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, p=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year. Interpretation Occupational exposures account for a substantial proportion of adult asthma incidence. The increased risk of asthma after inhalation accidents suggests that workers who have such accidents should be monitored closely.	27	201	2007	6	10.1016/S0140-6736(07)61164-7	General & Internal Medicine
Experimentally induced recruitment of plasmacytoid (CD123(high)) dendritic cells in human nasal allergy. Recent evidence suggests that the previously enigmatic cell type designated plasmacytoid monocytes can function as dendritic cells and contribute substantially to both innate and adaptive immunity. This cell type has previously been described only in bone marrow, blood, and organized lymphoid tissue, but not at effector sites with direct Ag exposure such as the mucosae, Plasmacytoid dendritic cells (P-DCs) matured in vitro can induce T cells to produce allergy-promoting Th2 cytokines; therefore, their possible occurrence in nasal mucosa during experimentally elicited allergic rhinitis was examined. Patients with silent nasal allergy were challenged topically with relevant allergen daily for 7 days. Biopsy specimens as well as blood samples were obtained before and during such provocation, and P-DCs were identified by their high expression of CD123 (IL3R alpha-chain), together with CD45RA, Our results showed that P-DCs were present in low and variable numbers in normal nasal mucosa but increased dramatically during the allergic reaction. This accumulation concurred with the expression of the L-selectin ligand peripheral lymph node addressin on the mucosal vascular endothelium. The latter observation was particularly interesting in view of the high levels of L-selectin on circulating P-DC precursors and of previous reports suggesting that these cells ran enter organized lymphoid tissue via high endothelial venules (which express peripheral lymph node addressin constitutively). Together, our findings suggested that P-DCs are involved in the triggering of airway allergy and that they are directed to allergic lesions by adhesion molecules that normally mediate leukocyte extravasation in organized lymphoid tissue.. endothelial adhesion molecules| t-cells| lymph-node| human blood| expression| interferon| monocytes| origin| mxa| lymphadenitis.	OCT 1-2000	endothelial adhesion molecules| t-cells| lymph-node| human blood| expression| interferon| monocytes| origin| mxa| lymphadenitis	Jahnsen, FL; Lund-Johansen, F; Dunne, JF; Farkas, L; Haye, R; Brandtzaeg, P	Experimentally induced recruitment of plasmacytoid (CD123(high)) dendritic cells in human nasal allergy		JOURNAL OF IMMUNOLOGY		ENDOTHELIAL ADHESION MOLECULES; T-CELLS; LYMPH-NODE; HUMAN BLOOD; EXPRESSION; INTERFERON; MONOCYTES; ORIGIN; MXA; LYMPHADENITIS	Recent evidence suggests that the previously enigmatic cell type designated plasmacytoid monocytes can function as dendritic cells and contribute substantially to both innate and adaptive immunity. This cell type has previously been described only in bone marrow, blood, and organized lymphoid tissue, but not at effector sites with direct Ag exposure such as the mucosae, Plasmacytoid dendritic cells (P-DCs) matured in vitro can induce T cells to produce allergy-promoting Th2 cytokines; therefore, their possible occurrence in nasal mucosa during experimentally elicited allergic rhinitis was examined. Patients with silent nasal allergy were challenged topically with relevant allergen daily for 7 days. Biopsy specimens as well as blood samples were obtained before and during such provocation, and P-DCs were identified by their high expression of CD123 (IL3R alpha-chain), together with CD45RA, Our results showed that P-DCs were present in low and variable numbers in normal nasal mucosa but increased dramatically during the allergic reaction. This accumulation concurred with the expression of the L-selectin ligand peripheral lymph node addressin on the mucosal vascular endothelium. The latter observation was particularly interesting in view of the high levels of L-selectin on circulating P-DC precursors and of previous reports suggesting that these cells ran enter organized lymphoid tissue via high endothelial venules (which express peripheral lymph node addressin constitutively). Together, our findings suggested that P-DCs are involved in the triggering of airway allergy and that they are directed to allergic lesions by adhesion molecules that normally mediate leukocyte extravasation in organized lymphoid tissue.	36	201	2000	7		Immunology
Evidence of airway inflammation and remodeling in ski athletes with and without bronchial hyperresponsiveness to methacholine. Asthma-like symptoms, methacholine hyperresponsiveness, and use of asthma medication are prevalent in elite cross-country skiers. We quantitated mucosal inflammatory cell infiltration and tenascin expression in the subepithelial basement membrane in endobronchial biopsy specimens of the proximal airways from 40 elite, competitive skiers (mean: 17.5; range: 16 to 20 yr) without a diagnosis of asthma, in 12 subjects with mild asthma, and in 12 healthy controls, through immunohistochemistry and indirect immunofluorescence, respectively. All of the subjects were nonsmokers. T-lymphocyte, macrophage, and eosinophil counts were, respectively, greater by 43-fold (p < 0.001), 26-fold (p < 0.001), and twofold (p < 0.001) in skiers, and by 70-fold (p < 0.001), 63-fold (p < 0.001), and eightfold (p < 0.001) in asthmatic subjects than in controls. In skiers, neutrophil counts were more than twofold greater than in asthmatic subjects, and mast cell counts were not significantly different than in controls. Tenascin expression (as measured through the thickness of the tenascin-specific immunoreactivity band in the basement membrane) was increased in skiers (median: 6.7 mu m; interquartile range [IQR]: 5.3 to 8.5 mu m, p < 0.001) and asthmatic subjects (mean: 8.8 mu m; IQR: 7.2 to 10.8 mu m, p < 0.001) compared with controls (mean: 0.8 mu m; IQR: 0 to 3.1 mu m) and did not correlate with inflammatory cell counts. Inflammatory changes were present irrespective of asthmalike symptoms, hyperresponsiveness, or atopy. Prolonged repeated exposure of the airways to inadequately conditioned air may induce inflammation and remodeling in competitive skiers.. cross-country skiers| inhaled histamine| asthma| responsiveness| lymphocytes| macrophages| eosinophils| prevalence| symptoms| tenascin.	JUN-2000	cross-country skiers| inhaled histamine| asthma| responsiveness| lymphocytes| macrophages| eosinophils| prevalence| symptoms| tenascin	Karjalainen, EM; Laitinen, A; Sue-Chu, M; Altraja, A; Bjermer, L; Laitinen, LA	Evidence of airway inflammation and remodeling in ski athletes with and without bronchial hyperresponsiveness to methacholine		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		CROSS-COUNTRY SKIERS; INHALED HISTAMINE; ASTHMA; RESPONSIVENESS; LYMPHOCYTES; MACROPHAGES; EOSINOPHILS; PREVALENCE; SYMPTOMS; TENASCIN	Asthma-like symptoms, methacholine hyperresponsiveness, and use of asthma medication are prevalent in elite cross-country skiers. We quantitated mucosal inflammatory cell infiltration and tenascin expression in the subepithelial basement membrane in endobronchial biopsy specimens of the proximal airways from 40 elite, competitive skiers (mean: 17.5; range: 16 to 20 yr) without a diagnosis of asthma, in 12 subjects with mild asthma, and in 12 healthy controls, through immunohistochemistry and indirect immunofluorescence, respectively. All of the subjects were nonsmokers. T-lymphocyte, macrophage, and eosinophil counts were, respectively, greater by 43-fold (p < 0.001), 26-fold (p < 0.001), and twofold (p < 0.001) in skiers, and by 70-fold (p < 0.001), 63-fold (p < 0.001), and eightfold (p < 0.001) in asthmatic subjects than in controls. In skiers, neutrophil counts were more than twofold greater than in asthmatic subjects, and mast cell counts were not significantly different than in controls. Tenascin expression (as measured through the thickness of the tenascin-specific immunoreactivity band in the basement membrane) was increased in skiers (median: 6.7 mu m; interquartile range [IQR]: 5.3 to 8.5 mu m, p < 0.001) and asthmatic subjects (mean: 8.8 mu m; IQR: 7.2 to 10.8 mu m, p < 0.001) compared with controls (mean: 0.8 mu m; IQR: 0 to 3.1 mu m) and did not correlate with inflammatory cell counts. Inflammatory changes were present irrespective of asthmalike symptoms, hyperresponsiveness, or atopy. Prolonged repeated exposure of the airways to inadequately conditioned air may induce inflammation and remodeling in competitive skiers.	22	201	2000	6		General & Internal Medicine; Respiratory System
Peanut allergy: Emerging concepts and approaches for an apparent epidemic. Peanut allergy is typically lifelong, often severe, and potentially fatal. Because reactions can occur from small amounts, the allergy presents patients with significant obstacles to avoid allergic reactions. In North America and the United Kingdom, prevalence rates among schoolchildren are now in excess of 1%, framing an increasing public health concern and raising research questions about environmental, immunologic, and genetic factors that may influence outcomes of peanut allergy. This review focuses on recent observations that continue to question the influences of maternal and infant diet on outcomes of peanut allergy, and explore how peanut may be uniquely suited to induce an allergic response. We highlight studies that affect current diagnosis, management, and the nature of advice that can be provided to patients, including the utility of diagnostic tests. doses that elicit reactions, characteristics of reactions from exposure, issues of cross-reactivity, concerns about peanut contamination of manufactured goods, and the natural course of the allergy. Clinical, molecular, and immunologic advances are reviewed, highlighting research discoveries that influence strategies for improved diagnosis, prevention, and treatment. Among the therapeutic strategies reviewed are sublingual and oral immunotherapy, anti-IgE, Chinese herbal medicine, and vaccine strategies.. food allergy| food hypersensitivity| peanut allergy| food allergens| anaphylaxis| treatment|tree nut allergy| controlled food challenges| cows milk allergy| skin prick tests| murine model| double-blind| in-vitro| anaphylactic reactions| immune-response| oral tolerance.	SEP-2007	food allergy| food hypersensitivity| peanut allergy| food allergens| anaphylaxis| treatment|tree nut allergy| controlled food challenges| cows milk allergy| skin prick tests| murine model| double-blind| in-vitro| anaphylactic reactions| immune-response| oral tolerance	Sicherer, SH; Sampson, HA	Peanut allergy: Emerging concepts and approaches for an apparent epidemic		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	food allergy; food hypersensitivity; peanut allergy; food allergens; anaphylaxis; treatment	TREE NUT ALLERGY; CONTROLLED FOOD CHALLENGES; COWS MILK ALLERGY; SKIN PRICK TESTS; MURINE MODEL; DOUBLE-BLIND; IN-VITRO; ANAPHYLACTIC REACTIONS; IMMUNE-RESPONSE; ORAL TOLERANCE	Peanut allergy is typically lifelong, often severe, and potentially fatal. Because reactions can occur from small amounts, the allergy presents patients with significant obstacles to avoid allergic reactions. In North America and the United Kingdom, prevalence rates among schoolchildren are now in excess of 1%, framing an increasing public health concern and raising research questions about environmental, immunologic, and genetic factors that may influence outcomes of peanut allergy. This review focuses on recent observations that continue to question the influences of maternal and infant diet on outcomes of peanut allergy, and explore how peanut may be uniquely suited to induce an allergic response. We highlight studies that affect current diagnosis, management, and the nature of advice that can be provided to patients, including the utility of diagnostic tests. doses that elicit reactions, characteristics of reactions from exposure, issues of cross-reactivity, concerns about peanut contamination of manufactured goods, and the natural course of the allergy. Clinical, molecular, and immunologic advances are reviewed, highlighting research discoveries that influence strategies for improved diagnosis, prevention, and treatment. Among the therapeutic strategies reviewed are sublingual and oral immunotherapy, anti-IgE, Chinese herbal medicine, and vaccine strategies.	143	200	2007	13	10.1016/j.jaci.2007.07.015	Allergy; Immunology
Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children. Airway inflammation in asthma is not measured routinely in clinical practice. Fractional exhaled nitric oxide (FENO), a marker of airway inflammation, is increasingly used as an outcome measure in asthma intervention studies and yet the reproducibility of FENO measurements is unknown. The reproducibility, day-to-day, diurnal variation and perception of standardised FENO measurements were examined in 59 subjects (40 children aged 7-13 yrs and 19 adults aged 18-60 yrs), both healthy (n=30) and with mild (n=29) asthma. FENO was measured on five consecutive days (four measurements on the same day) for adults and twice on the same day for children. The coefficient of reproducibility expressed as the mean pooled standard deviation (n=59, 675 estimations) was 2.11 parts per billion (ppb) and intraclass correlation coefficient was 0.99 in both children and adults. FENO was significantly higher in asthma subjects (32.3 ppb) than in healthy subjects (16.3 ppb). There was no diurnal or day-to-day variation, or a learning effect, as the result of FEND measurements were identical at results of the beginning and at the end of the study. It was concluded that fractional exhaled nitric oxide measurements are simple, reproducible, free from diurnal and day-to-day variation, and acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician.. asthma| exhaled nitric oxide| fractional exhaled nitric oxide measurements|sputum induction| atopic asthma| flow| air.	MAR-2003	asthma| exhaled nitric oxide| fractional exhaled nitric oxide measurements|sputum induction| atopic asthma| flow| air	Kharitonov, SA; Gonio, F; Kelly, C; Meah, S; Barnes, PJ	Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children		EUROPEAN RESPIRATORY JOURNAL	asthma; exhaled nitric oxide; fractional exhaled nitric oxide measurements	SPUTUM INDUCTION; ATOPIC ASTHMA; FLOW; AIR	Airway inflammation in asthma is not measured routinely in clinical practice. Fractional exhaled nitric oxide (FENO), a marker of airway inflammation, is increasingly used as an outcome measure in asthma intervention studies and yet the reproducibility of FENO measurements is unknown. The reproducibility, day-to-day, diurnal variation and perception of standardised FENO measurements were examined in 59 subjects (40 children aged 7-13 yrs and 19 adults aged 18-60 yrs), both healthy (n=30) and with mild (n=29) asthma. FENO was measured on five consecutive days (four measurements on the same day) for adults and twice on the same day for children. The coefficient of reproducibility expressed as the mean pooled standard deviation (n=59, 675 estimations) was 2.11 parts per billion (ppb) and intraclass correlation coefficient was 0.99 in both children and adults. FENO was significantly higher in asthma subjects (32.3 ppb) than in healthy subjects (16.3 ppb). There was no diurnal or day-to-day variation, or a learning effect, as the result of FEND measurements were identical at results of the beginning and at the end of the study. It was concluded that fractional exhaled nitric oxide measurements are simple, reproducible, free from diurnal and day-to-day variation, and acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician.	30	200	2003	6	10.1183/09031936.03.00066903	Respiratory System
IL-5 promotes eosinophil trafficking to the esophagus. Eosinophil infiltration into the esophagus occurs in a wide range of diseases; however, the underlying pathophysiological mechanisms involved are largely unknown. We now report that the Th2 cytokine, IL-5, is necessary and sufficient for the induction of eosinophil trafficking to the esophagus. We show that transgenic mice overexpressing IL-5 under the control of a T cell (CD2) or a small intestinal enterocyte (fatty acid-binding protein) promoter have markedly increased eosinophil numbers in the esophagus. For example, esophageal eosinophil levels are 1.9 +/- 0.9 and 121 +/- 14 eosinophils/mm(2) in wild-type and CD2-IL-5-transgenic mice, respectively. Consistent with this effect being mediated by a systemic mechanism, pharmacological administration of IL-5 via a miniosmotic pump in the peritoneal cavity resulted in blood and esophageal eosinophilia. To examine the role of IL-5 in oral Ag-induced esophageal eosinophilia, eosinophilic esophagitis was induced by allergen exposure in IL-5-deficient and wild-type mice. Importantly, IL-5-deficient mice were resistant to eosinophilic esophagitis. Finally, we examined the role of eotaxin when IL-5 was overproduced in vivo. Esophageal eosinophil levels in CD2-IL-5-transgenic mice were found to decrease 15-fold in the absence of the cotaxin gene; however, esophageal eosinophil numbers in eotaxin-deficient IL-5-transgenic mice still remained higher than wild-type nice. In conclusion, these studies demonstrate a central role for IL-5 in inducing eosinophil trafficking to the esophagus.. gastroesophageal reflux| tissue eosinophilia| chemokine eotaxin| transgenic mice| in-vivo| interleukin-5| acid| children| disease| corticosteroids.	MAR 1-2002	gastroesophageal reflux| tissue eosinophilia| chemokine eotaxin| transgenic mice| in-vivo| interleukin-5| acid| children| disease| corticosteroids	Mishra, A; Hogan, SP; Brandt, EB; Rothenberg, ME	IL-5 promotes eosinophil trafficking to the esophagus		JOURNAL OF IMMUNOLOGY		GASTROESOPHAGEAL REFLUX; TISSUE EOSINOPHILIA; CHEMOKINE EOTAXIN; TRANSGENIC MICE; IN-VIVO; INTERLEUKIN-5; ACID; CHILDREN; DISEASE; CORTICOSTEROIDS	Eosinophil infiltration into the esophagus occurs in a wide range of diseases; however, the underlying pathophysiological mechanisms involved are largely unknown. We now report that the Th2 cytokine, IL-5, is necessary and sufficient for the induction of eosinophil trafficking to the esophagus. We show that transgenic mice overexpressing IL-5 under the control of a T cell (CD2) or a small intestinal enterocyte (fatty acid-binding protein) promoter have markedly increased eosinophil numbers in the esophagus. For example, esophageal eosinophil levels are 1.9 +/- 0.9 and 121 +/- 14 eosinophils/mm(2) in wild-type and CD2-IL-5-transgenic mice, respectively. Consistent with this effect being mediated by a systemic mechanism, pharmacological administration of IL-5 via a miniosmotic pump in the peritoneal cavity resulted in blood and esophageal eosinophilia. To examine the role of IL-5 in oral Ag-induced esophageal eosinophilia, eosinophilic esophagitis was induced by allergen exposure in IL-5-deficient and wild-type mice. Importantly, IL-5-deficient mice were resistant to eosinophilic esophagitis. Finally, we examined the role of eotaxin when IL-5 was overproduced in vivo. Esophageal eosinophil levels in CD2-IL-5-transgenic mice were found to decrease 15-fold in the absence of the cotaxin gene; however, esophageal eosinophil numbers in eotaxin-deficient IL-5-transgenic mice still remained higher than wild-type nice. In conclusion, these studies demonstrate a central role for IL-5 in inducing eosinophil trafficking to the esophagus.	36	199	2002	6		Immunology
Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide. The potential role of respiratory infections in altering the development of atopy and asthma is complex. Infections have been suggested to be effective in preventing the induction of T-helper 2-polarized allergen-specific immunity in early life, but also to exacerbate asthma in older, sensitized individuals. The mechanism(s) underlying these effects are poorly defined. The aim of this work was to determine the influence of lipopolysaccharide (LPS) exposure on the development of sensitization to allergen and the response to allergen challenge in vivo. Piebald-Virol-Glaxo rats were exposed to a single aerosol of LPS 1 d before or 1, 2, 4, 6, 8, or 10 d after sensitization with ovalbumin (OVA). On Day 11 animals were exposed to 1% OVA and responses to allergen were measured 24 h later, monitoring inflammatory cell influx and microvascular leakage into bronchoalveolar lavage (BAL) fluid as well as pulmonary responses to methacholine using the forced oscillation technique. Histologic analysis was included to complement the BAL results. Single aerosol exposure to LPS 1 d before and up to 4 d after intraperitoneal injection of OVA protected against the development of OVA-specific immunoglobulin tig) E. LPS exposure 6, 8, or 10 d after sensitization further exacerbated the OVA-induced cellular influx, resulting in neutrophilia and increased Evans Blue dye leakage with no effect on serum IgE levels. In addition, LPS abolished the OVA-induced hyperresponsiveness in sensitized animals when given 18 h after OVA challenge. This study demonstrates that exposure to LPS can modify the development of allergic inflammation in vivo by two independent mechanisms. Exposure early in the sensitization process, up to Day 6 after exposure to allergen, prevented allergen sensitization. Exposure to LPS after allergen challenge in sensitized animals abolished the hyperresponsiveness and modified the inflammatory cell influx characteristic of late-phase response to allergen.. induced bronchial hyperresponsiveness| brown-norway rats| airway hyperresponsiveness| human-lymphocytes| viral-infections| nitric-oxide| asthma| endotoxin| ige| childhood.	MAY-2000	induced bronchial hyperresponsiveness| brown-norway rats| airway hyperresponsiveness| human-lymphocytes| viral-infections| nitric-oxide| asthma| endotoxin| ige| childhood	Tulic, MK; Wale, JL; Holt, PG; Sly, PD	Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		INDUCED BRONCHIAL HYPERRESPONSIVENESS; BROWN-NORWAY RATS; AIRWAY HYPERRESPONSIVENESS; HUMAN-LYMPHOCYTES; VIRAL-INFECTIONS; NITRIC-OXIDE; ASTHMA; ENDOTOXIN; IGE; CHILDHOOD	The potential role of respiratory infections in altering the development of atopy and asthma is complex. Infections have been suggested to be effective in preventing the induction of T-helper 2-polarized allergen-specific immunity in early life, but also to exacerbate asthma in older, sensitized individuals. The mechanism(s) underlying these effects are poorly defined. The aim of this work was to determine the influence of lipopolysaccharide (LPS) exposure on the development of sensitization to allergen and the response to allergen challenge in vivo. Piebald-Virol-Glaxo rats were exposed to a single aerosol of LPS 1 d before or 1, 2, 4, 6, 8, or 10 d after sensitization with ovalbumin (OVA). On Day 11 animals were exposed to 1% OVA and responses to allergen were measured 24 h later, monitoring inflammatory cell influx and microvascular leakage into bronchoalveolar lavage (BAL) fluid as well as pulmonary responses to methacholine using the forced oscillation technique. Histologic analysis was included to complement the BAL results. Single aerosol exposure to LPS 1 d before and up to 4 d after intraperitoneal injection of OVA protected against the development of OVA-specific immunoglobulin tig) E. LPS exposure 6, 8, or 10 d after sensitization further exacerbated the OVA-induced cellular influx, resulting in neutrophilia and increased Evans Blue dye leakage with no effect on serum IgE levels. In addition, LPS abolished the OVA-induced hyperresponsiveness in sensitized animals when given 18 h after OVA challenge. This study demonstrates that exposure to LPS can modify the development of allergic inflammation in vivo by two independent mechanisms. Exposure early in the sensitization process, up to Day 6 after exposure to allergen, prevented allergen sensitization. Exposure to LPS after allergen challenge in sensitized animals abolished the hyperresponsiveness and modified the inflammatory cell influx characteristic of late-phase response to allergen.	45	199	2000	9		Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Biology of diesel exhaust effects on respiratory function. In recent decades, clinicians and scientists have witnessed a significant increase in the prevalence of allergic rhinitis and asthma. The factors underlying this phenomenon are clearly complex; however, this rapid increase in the burden or atopic disease has undeniably occurred in parallel with rapid industrialization and urbanization in many parts or the world. Consequently, more people are exposed to air pollutants than at any point in human history. Worldwide, increases in allergic respiratory disease have mainly been observed in urban communities. Epidemiologic and clinical investigations have suggested a strong link between particulate air pollution and detrimental health effects, including cardiopulmonary morbidity and mortality. The purpose of this review is to provide an evidence-based summary of the health effects of air pollutants on asthma, focusing on diesel exhaust particles (DEPs) as a model particulate air pollutant. An overview of observational and experimental studies linking DEPs and asthma will be provided, followed by consideration of the mechanisms underlying DEP-induced inflammation and a brief discussion of future research and clinical directions.. air pollution| diesel exhaust particles| allergy| asthma| oxidative stress| respiratory effects|bronchial epithelial-cells| glutathione-s-transferase| particulate air-pollution| placebo-controlled trial| oxidative stress| in-vivo| bronchoalveolar lavage| asthmatic-patients| childhood asthma| nasal challenge.	FEB-2005	air pollution| diesel exhaust particles| allergy| asthma| oxidative stress| respiratory effects|bronchial epithelial-cells| glutathione-s-transferase| particulate air-pollution| placebo-controlled trial| oxidative stress| in-vivo| bronchoalveolar lavage| asthmatic-patients| childhood asthma| nasal challenge	Riedl, M; Diaz-Sanchez, D	Biology of diesel exhaust effects on respiratory function		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	air pollution; diesel exhaust particles; allergy; asthma; oxidative stress; respiratory effects	BRONCHIAL EPITHELIAL-CELLS; GLUTATHIONE-S-TRANSFERASE; PARTICULATE AIR-POLLUTION; PLACEBO-CONTROLLED TRIAL; OXIDATIVE STRESS; IN-VIVO; BRONCHOALVEOLAR LAVAGE; ASTHMATIC-PATIENTS; CHILDHOOD ASTHMA; NASAL CHALLENGE	In recent decades, clinicians and scientists have witnessed a significant increase in the prevalence of allergic rhinitis and asthma. The factors underlying this phenomenon are clearly complex; however, this rapid increase in the burden or atopic disease has undeniably occurred in parallel with rapid industrialization and urbanization in many parts or the world. Consequently, more people are exposed to air pollutants than at any point in human history. Worldwide, increases in allergic respiratory disease have mainly been observed in urban communities. Epidemiologic and clinical investigations have suggested a strong link between particulate air pollution and detrimental health effects, including cardiopulmonary morbidity and mortality. The purpose of this review is to provide an evidence-based summary of the health effects of air pollutants on asthma, focusing on diesel exhaust particles (DEPs) as a model particulate air pollutant. An overview of observational and experimental studies linking DEPs and asthma will be provided, followed by consideration of the mechanisms underlying DEP-induced inflammation and a brief discussion of future research and clinical directions.	110	198	2005	8	10.1016/j.jaci.2004.11.047	Allergy; Immunology
Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling. It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4(+) lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposecl mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HIDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly.. allergy and immunology| animal| asthma| models|murine model| allergen der-p-1| lung inflammation| epithelial-cells| gm-csf| asthma| hyperresponsiveness| responsiveness| sensitization| eosinophilia.	FEB 1-2004	allergy and immunology| animal| asthma| models|murine model| allergen der-p-1| lung inflammation| epithelial-cells| gm-csf| asthma| hyperresponsiveness| responsiveness| sensitization| eosinophilia	Johnson, JR; Wiley, RE; Fattouh, R; Swirski, FK; Gajewska, BU; Coyle, AJ; Gutierrez-Ramos, JC; Ellis, R; Inman, MD; Jordana, M	Continuous exposure to house dust mite elicits chronic airway inflammation and structural remodeling		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	allergy and immunology; animal; asthma; models	MURINE MODEL; ALLERGEN DER-P-1; LUNG INFLAMMATION; EPITHELIAL-CELLS; GM-CSF; ASTHMA; HYPERRESPONSIVENESS; RESPONSIVENESS; SENSITIZATION; EOSINOPHILIA	It is now fully appreciated that asthma is a disease of a chronic nature resulting from intermittent or continued aeroallergen exposure leading to airway inflammation. To investigate responses to continuous antigen exposure, mice were exposed to either house dust mite extract (HDM) or ovalbumin intranasally for five consecutive days, followed by 2 days of rest, for up to seven consecutive weeks. Continuous exposure to HDM, unlike ovalbumin, elicited severe and persistent eosinophilic airway inflammation. Flow cytometric analysis demonstrated an accumulation of CD4(+) lymphocytes in the lung with elevated expression of inducible costimulator a marker of T cell activation, and of T1/ST2, a marker of helper T Type 2 effector cells. We also detected increased and sustained production of helper T cell Type 2-associated cytokines by splenocytes of HDM-exposecl mice on in vitro HDM recall. Histologic analysis of the lung showed evidence of airway remodeling in mice exposed to HIDM, with goblet cell hyperplasia, collagen deposition, and peribronchial accumulation of contractile tissue. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. Finally, these responses were studied for up to 9 weeks after cessation of HDM exposure. We observed that whereas airway inflammation resolved fully, the remodeling changes did not resolve and airway hyperreactivity resolved only partly.	26	198	2004	8	10.1164/rccm.200308-1094OC	General & Internal Medicine; Respiratory System
Treating allergic rhinitis in patients with comorbid asthma: The risk of asthma-related hospitalizations and emergency department visits. Background: Although asthma and allergic rhinitis commonly occur together, the nature of the association has yet to be determined. Treatments for one condition could potentially alleviate the coexisting condition. Objective: Patients with both allergic rhinitis and asthma were studied to test the hypothesis that treating allergic rhinitis reduces health care utilization for co-morbid asthma. Methods: A retrospective cohort study was carried out with 1994-1995 MarketScan claims data. The cohort was limited to patients with both allergic rhinitis and asthma, aged 12 to 60 years, who were continuously enrolled and had no evidence of chronic obstructive pulmonary disease. Allergic rhinitis treatment and asthma-related events (hospitalizations and emergency department visits) were identified. An incidence density ratio (IDR) associated with exposure to allergic rhinitis treatment was calculated. A multivariate Poisson regression was estimated, and the parameter estimates were transformed into IDRs for each explanatory variable. An allergic rhinitis treatment indicator was included in all regressions. Results: The study sample population consisted of 4944 patients with allergic asthma, approximately 73% of whom were treated for their allergic rhinitis. Asthma-related events occurred more often for the untreated group compared with the treated group, 6.6 % compared with 1.3 %. An IDR of 0.49 for the treatment group (P =.001) indicates that the risk of an asthma-related event for the treated group was about half that for the untreated group. Conclusion: In summary, those who were treated for allergic rhinitis have a significantly lower risk of subsequent asthma-related events (emergency department visits or hospitalizations) than those who were not treated.. allergic rhinitis| asthma| administrative claims analysis.	JAN-2002	allergic rhinitis| asthma| administrative claims analysis	Crystal-Peters, J; Neslusan, C; Crown, WH; Torres, A	Treating allergic rhinitis in patients with comorbid asthma: The risk of asthma-related hospitalizations and emergency department visits		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergic rhinitis; asthma; administrative claims analysis		Background: Although asthma and allergic rhinitis commonly occur together, the nature of the association has yet to be determined. Treatments for one condition could potentially alleviate the coexisting condition. Objective: Patients with both allergic rhinitis and asthma were studied to test the hypothesis that treating allergic rhinitis reduces health care utilization for co-morbid asthma. Methods: A retrospective cohort study was carried out with 1994-1995 MarketScan claims data. The cohort was limited to patients with both allergic rhinitis and asthma, aged 12 to 60 years, who were continuously enrolled and had no evidence of chronic obstructive pulmonary disease. Allergic rhinitis treatment and asthma-related events (hospitalizations and emergency department visits) were identified. An incidence density ratio (IDR) associated with exposure to allergic rhinitis treatment was calculated. A multivariate Poisson regression was estimated, and the parameter estimates were transformed into IDRs for each explanatory variable. An allergic rhinitis treatment indicator was included in all regressions. Results: The study sample population consisted of 4944 patients with allergic asthma, approximately 73% of whom were treated for their allergic rhinitis. Asthma-related events occurred more often for the untreated group compared with the treated group, 6.6 % compared with 1.3 %. An IDR of 0.49 for the treatment group (P =.001) indicates that the risk of an asthma-related event for the treated group was about half that for the untreated group. Conclusion: In summary, those who were treated for allergic rhinitis have a significantly lower risk of subsequent asthma-related events (emergency department visits or hospitalizations) than those who were not treated.	21	198	2002	6	10.1067/mai.2002.120554	Allergy; Immunology
Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. Background: Proteases in extracts of Aspergillus fumigatus cause epithelial cell desquamation and release of proinflammatory cytokines. Objective: We sought to assess protease activity in Alternaria alternata, Cladosporium herbarum, and Aspergillus fumigatus extracts and study the ability of these extracts to cause desquamation and release of proinflammatory cytokines from epithelial cells. Methods: Protease activities of the fungal extracts were quantified, Changes with respect to cell morphology, cell desquamation, and cytokine production (IL-6 and IL-8) were measured in the absence and presence of the fungal extracts in an airway-derived epithelial cell line (A549) and primary epithelial nasal cells. Results: Fungal proteases differentially induced morphologic changes, cell desquamation, and production of IL-6 and IL-8 in a dose- and time-dependent fashion. Alternaria alternata extracts induced cell shrinking and cell desquamation and strongly enhanced the production of IL-6 and IL-8 at higher concentrations. Aspergillus fumigatus extracts caused cell shrinking, cell desquamation, and production of IL-6 and IL-8, even at low concentrations. The Aspergillus fumigatus-derived extract groan on collagen medium induced a strong dose-dependent decline in cytokine production at higher concentrations. Cladosporium herbarum extracts did not induce morphologic changes or cell desquamation but enhanced IL-6 and IL-8 productions at higher concentrations. The dependence of these effects on intact protease activity was shown by their abrogation by protease inhibitors. Conclusion: Proteases present in fungal extracts interact with epithelial cells, leading to morphologic changes, cell desquamation, and induction of proinflammatory cytokines. It is proposed that these fungal proteases may activate epithelial cells through a protease-activated receptor type 2-driven mechanism.. fungal| proteases| epithelial cells| cytokines| desquamation| protease-activated receptor| asthma| sensitization|volumetric aerobiological survey| house-dust mite| mold allergy| northeast netherlands| conidial fungi| aspergillus| asthma| detachment| diagnosis| sensitization.	JUN-2000	fungal| proteases| epithelial cells| cytokines| desquamation| protease-activated receptor| asthma| sensitization|volumetric aerobiological survey| house-dust mite| mold allergy| northeast netherlands| conidial fungi| aspergillus| asthma| detachment| diagnosis| sensitization	Kauffman, HF; Tomee, JFC; van de Riet, MA; Timmerman, AJB; Borger, P	Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	fungal; proteases; epithelial cells; cytokines; desquamation; protease-activated receptor; asthma; sensitization	VOLUMETRIC AEROBIOLOGICAL SURVEY; HOUSE-DUST MITE; MOLD ALLERGY; NORTHEAST NETHERLANDS; CONIDIAL FUNGI; ASPERGILLUS; ASTHMA; DETACHMENT; DIAGNOSIS; SENSITIZATION	Background: Proteases in extracts of Aspergillus fumigatus cause epithelial cell desquamation and release of proinflammatory cytokines. Objective: We sought to assess protease activity in Alternaria alternata, Cladosporium herbarum, and Aspergillus fumigatus extracts and study the ability of these extracts to cause desquamation and release of proinflammatory cytokines from epithelial cells. Methods: Protease activities of the fungal extracts were quantified, Changes with respect to cell morphology, cell desquamation, and cytokine production (IL-6 and IL-8) were measured in the absence and presence of the fungal extracts in an airway-derived epithelial cell line (A549) and primary epithelial nasal cells. Results: Fungal proteases differentially induced morphologic changes, cell desquamation, and production of IL-6 and IL-8 in a dose- and time-dependent fashion. Alternaria alternata extracts induced cell shrinking and cell desquamation and strongly enhanced the production of IL-6 and IL-8 at higher concentrations. Aspergillus fumigatus extracts caused cell shrinking, cell desquamation, and production of IL-6 and IL-8, even at low concentrations. The Aspergillus fumigatus-derived extract groan on collagen medium induced a strong dose-dependent decline in cytokine production at higher concentrations. Cladosporium herbarum extracts did not induce morphologic changes or cell desquamation but enhanced IL-6 and IL-8 productions at higher concentrations. The dependence of these effects on intact protease activity was shown by their abrogation by protease inhibitors. Conclusion: Proteases present in fungal extracts interact with epithelial cells, leading to morphologic changes, cell desquamation, and induction of proinflammatory cytokines. It is proposed that these fungal proteases may activate epithelial cells through a protease-activated receptor type 2-driven mechanism.	37	198	2000	9	10.1067/mai.2000.106210	Allergy; Immunology
Lymph node trafficking and antigen presentation by endobronchial eosinophils. Because eosinophils recruited into the airways in allergic diseases are exposed to inhaled allergens, we evaluated whether eosinophils within the endobronchial lumen can function in vivo as antigen-presenting cells for inhaled antigens. We recovered eosinophils from the airways after aerosol antigen challenge in sensitized mice or from the peritoneal cavities of IL-5 transgenic mice and fluorescently labeled these cells ex vivo. These labeled cells, instilled intratracheally into normal mice, migrated into draining paratracheal lymph nodes and localized to T cell-rich paracortical areas. The homing of airway eosinophils to lymph nodes was not governed by eotaxin, because CCR3(-/-) and CCR3(+/+) eosinophils migrated identically. Airway eosinophils, recovered after inhalational antigen challenge in sensitized mice, expressed MHC class II and costimulatory CD80 and CD86 proteins and functioned in vitro as CD80- and CD86-dependent, antigen-specific, antigen-presenting cells. Moreover, when instilled into the airways of antigen-sensitized recipient mice, airway eosinophils recovered after inhalational antigen challenge stimulated antigen-specific CD4(+) T cell proliferation within paratracheal lymph nodes. Thus, eosinophils within the lumina of airways can process inhaled antigens, traffic to regional lymph nodes, and function in vivo as antigen-presenting cells to stimulate responses of CD4(+) T cells.. intercellular-adhesion molecule-1| t-cell clones| hla-dr| dendritic cells| alveolar macrophages| presenting cell| induced sputum| expression| asthma| lung.	APR-2000	intercellular-adhesion molecule-1| t-cell clones| hla-dr| dendritic cells| alveolar macrophages| presenting cell| induced sputum| expression| asthma| lung	Shi, HZ; Humbles, A; Gerard, C; Jin, Z; Weller, PF	Lymph node trafficking and antigen presentation by endobronchial eosinophils		JOURNAL OF CLINICAL INVESTIGATION		INTERCELLULAR-ADHESION MOLECULE-1; T-CELL CLONES; HLA-DR; DENDRITIC CELLS; ALVEOLAR MACROPHAGES; PRESENTING CELL; INDUCED SPUTUM; EXPRESSION; ASTHMA; LUNG	Because eosinophils recruited into the airways in allergic diseases are exposed to inhaled allergens, we evaluated whether eosinophils within the endobronchial lumen can function in vivo as antigen-presenting cells for inhaled antigens. We recovered eosinophils from the airways after aerosol antigen challenge in sensitized mice or from the peritoneal cavities of IL-5 transgenic mice and fluorescently labeled these cells ex vivo. These labeled cells, instilled intratracheally into normal mice, migrated into draining paratracheal lymph nodes and localized to T cell-rich paracortical areas. The homing of airway eosinophils to lymph nodes was not governed by eotaxin, because CCR3(-/-) and CCR3(+/+) eosinophils migrated identically. Airway eosinophils, recovered after inhalational antigen challenge in sensitized mice, expressed MHC class II and costimulatory CD80 and CD86 proteins and functioned in vitro as CD80- and CD86-dependent, antigen-specific, antigen-presenting cells. Moreover, when instilled into the airways of antigen-sensitized recipient mice, airway eosinophils recovered after inhalational antigen challenge stimulated antigen-specific CD4(+) T cell proliferation within paratracheal lymph nodes. Thus, eosinophils within the lumina of airways can process inhaled antigens, traffic to regional lymph nodes, and function in vivo as antigen-presenting cells to stimulate responses of CD4(+) T cells.	41	198	2000	9	10.1172/JCI8945	Research & Experimental Medicine
Mast cells are required for experimental oral allergen-induced diarrhea. Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and FcepsilonRI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.. immunoglobulin-e receptor| fc-gamma riii| systemic-anaphylaxis| trichinella-spiralis| tryptase levels| t-cell| inflammation| ige| histamine| mice.	DEC-2003	immunoglobulin-e receptor| fc-gamma riii| systemic-anaphylaxis| trichinella-spiralis| tryptase levels| t-cell| inflammation| ige| histamine| mice	Brandt, EB; Strait, RT; Hershko, D; Wang, Q; Muntel, EE; Scribner, TA; Zimmermann, N; Finkelman, FD; Rothenberg, ME	Mast cells are required for experimental oral allergen-induced diarrhea		JOURNAL OF CLINICAL INVESTIGATION		IMMUNOGLOBULIN-E RECEPTOR; FC-GAMMA RIII; SYSTEMIC-ANAPHYLAXIS; TRICHINELLA-SPIRALIS; TRYPTASE LEVELS; T-CELL; INFLAMMATION; IGE; HISTAMINE; MICE	Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and FcepsilonRI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.	49	197	2003	12	10.1172/JCI19785	Research & Experimental Medicine
Impacts of climate change on aeroallergens: past and future. Human activities are resulting in increases in atmospheric greenhouse gases, such as carbon dioxide, and changes in global climate. These, in turn, are likely to have had, and will continue to have, impacts on human health. While such impacts have received increasing attention in recent years, the impacts of climate change on aeroallergens and related allergic diseases have been somewhat neglected. Despite this, a number of studies have revealed potential impacts of climate change on aeroallergens that may have enormous clinical and public health significance. The purpose of this review is to synthesize this work and to outline a number of research challenges in this area. There is now considerable evidence to suggest that climate change will have, and has already had, impacts on aeroallergens. These include impacts on pollen amount, pollen allergenicity, pollen season, plant and pollen distribution, and other plant attributes. There is also some evidence of impacts on other aeroallergens, such as mould spores. There are many research challenges along the road to a more complete understanding of the impacts of climate change on aeroallergens and allergic diseases such as asthma and hayfever. It is important that public health authorities and allergy practitioners be aware of these changes in the environment, and that research scientists embrace the challenges that face further work in this area.. allergen| carbon dioxide| climate change| distribution| mould| plant| pollen| season| spore| temperature|ragweed ambrosia-artemisiifolia| outdoor air-pollution| birch pollen seasons| public-health| respiratory allergy| airborne pollen| co2 enrichment| common ragweed| weather| europe.	OCT-2004	allergen| carbon dioxide| climate change| distribution| mould| plant| pollen| season| spore| temperature|ragweed ambrosia-artemisiifolia| outdoor air-pollution| birch pollen seasons| public-health| respiratory allergy| airborne pollen| co2 enrichment| common ragweed| weather| europe	Beggs, PJ	Impacts of climate change on aeroallergens: past and future		CLINICAL AND EXPERIMENTAL ALLERGY	allergen; carbon dioxide; climate change; distribution; mould; plant; pollen; season; spore; temperature	RAGWEED AMBROSIA-ARTEMISIIFOLIA; OUTDOOR AIR-POLLUTION; BIRCH POLLEN SEASONS; PUBLIC-HEALTH; RESPIRATORY ALLERGY; AIRBORNE POLLEN; CO2 ENRICHMENT; COMMON RAGWEED; WEATHER; EUROPE	Human activities are resulting in increases in atmospheric greenhouse gases, such as carbon dioxide, and changes in global climate. These, in turn, are likely to have had, and will continue to have, impacts on human health. While such impacts have received increasing attention in recent years, the impacts of climate change on aeroallergens and related allergic diseases have been somewhat neglected. Despite this, a number of studies have revealed potential impacts of climate change on aeroallergens that may have enormous clinical and public health significance. The purpose of this review is to synthesize this work and to outline a number of research challenges in this area. There is now considerable evidence to suggest that climate change will have, and has already had, impacts on aeroallergens. These include impacts on pollen amount, pollen allergenicity, pollen season, plant and pollen distribution, and other plant attributes. There is also some evidence of impacts on other aeroallergens, such as mould spores. There are many research challenges along the road to a more complete understanding of the impacts of climate change on aeroallergens and allergic diseases such as asthma and hayfever. It is important that public health authorities and allergy practitioners be aware of these changes in the environment, and that research scientists embrace the challenges that face further work in this area.	61	196	2004	7	10.1111/j.1365-2222.2004.02061.x	Allergy; Immunology
Anaphylaxis in the United States - An investigation into its epidemiology. Background: Anaphylaxis is a severe, life-threatening allergic reaction that affects both children and adults in the United States. However, data regarding the incidence and prevalence of anaphylaxis and the number of deaths caused by it are limited. Objective: To provide a better understanding of the magnitude of the problem of anaphylaxis in the United States. Methods: A thorough review of the current medical literature was conducted to obtain prevalence estimates on each of the 4 major subtypes of anaphylaxis (food, drugs, latex, and insect stings). We calculated an overall estimate of the risk of anaphylaxis by using only estimates that are specifically derived from epidemiologic studies measuring anaphylaxis in the general population. Results: Known rates or cases of anaphylaxis were 0.0004% for food, 0.7% to 10% for penicillin, 0.22% to 1% for radiocontrast media, and 0.5% to 5% after insect stings. There were 220 cases after latex exposure. Considering the 1999 US population of 272 million, the population at risk for anaphylaxis from food is 1099, from penicillin is 1.9 million to 27.2 million, from radiocontrast media is 22 000 to 100 000, from latex is 220, and from insect stings is 1.36 million to 13.6 million. These calculations yield a total of 1.29 million to 40.9 million individuals at risk of anaphylaxis. Conclusion: The occurrence of anaphylaxis in the US is not as rare as is generally believed. On the basis of our figures, the problem of anaphylaxis may, in fact, affect 1.21% to 15.04% of the US population.. contrast-media| adverse reactions| latex allergy| prevalence| risk| hypersensitivity| workers| rubber| peanut| drugs.	JAN 8-2001	contrast-media| adverse reactions| latex allergy| prevalence| risk| hypersensitivity| workers| rubber| peanut| drugs	Neugut, AI; Ghatak, AT; Miller, RL	Anaphylaxis in the United States - An investigation into its epidemiology		ARCHIVES OF INTERNAL MEDICINE		CONTRAST-MEDIA; ADVERSE REACTIONS; LATEX ALLERGY; PREVALENCE; RISK; HYPERSENSITIVITY; WORKERS; RUBBER; PEANUT; DRUGS	Background: Anaphylaxis is a severe, life-threatening allergic reaction that affects both children and adults in the United States. However, data regarding the incidence and prevalence of anaphylaxis and the number of deaths caused by it are limited. Objective: To provide a better understanding of the magnitude of the problem of anaphylaxis in the United States. Methods: A thorough review of the current medical literature was conducted to obtain prevalence estimates on each of the 4 major subtypes of anaphylaxis (food, drugs, latex, and insect stings). We calculated an overall estimate of the risk of anaphylaxis by using only estimates that are specifically derived from epidemiologic studies measuring anaphylaxis in the general population. Results: Known rates or cases of anaphylaxis were 0.0004% for food, 0.7% to 10% for penicillin, 0.22% to 1% for radiocontrast media, and 0.5% to 5% after insect stings. There were 220 cases after latex exposure. Considering the 1999 US population of 272 million, the population at risk for anaphylaxis from food is 1099, from penicillin is 1.9 million to 27.2 million, from radiocontrast media is 22 000 to 100 000, from latex is 220, and from insect stings is 1.36 million to 13.6 million. These calculations yield a total of 1.29 million to 40.9 million individuals at risk of anaphylaxis. Conclusion: The occurrence of anaphylaxis in the US is not as rare as is generally believed. On the basis of our figures, the problem of anaphylaxis may, in fact, affect 1.21% to 15.04% of the US population.	38	196	2001	7	10.1001/archinte.161.1.15	General & Internal Medicine
Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. The mechanisms by which signaling by the innate immune system controls susceptibility to allergy are poorly understood. In this report, we show that intragastric administration of a food allergen with a mucosal adjuvant induces allergen-specific IgE, elevated plasma histamine levels, and anaphylactic symptoms in three different strains of mice lacking a functional receptor for bacterial LPS (Toll-like receptor 4 (TLR4)), but not in MHC-matched or congenic controls. Susceptibility to allergy correlates with a Th2-biased cytokine response in both the mucosal (mesenteric lymph node and Peyer's patch) and systemic (spleen) tissues of TLR4-mutant or -deficient mice. TLR4-mutant mice are not inherently impaired in their ability to regulate Th1 cytokine production because they respond to stimulation via TLR9. Coadministration of CpG oligodeoxynucleotides during sensitization of TLR4-mutant mice with allergen plus CT abrogates anaphylactic symptoms and Ag-specific IgE, and results in a Th1-polarized cytokine response. When the composition of the bacterial flora is reduced and altered by antibiotic administration (beginning at 2 wk of age), TLR4 wild-type mice become as susceptible to the induction of allergy as their TLR4-mutant counterparts. Both allergen-specific IgE and Th2 cytokine responses are reduced in antibiotic-treated mice in which the flora has been allowed to repopulate. Taken together, our results suggest that TLR4-dependent signals provided by the intestinal commensal flora inhibit the development of allergic responses to food Ags.. major peanut allergen| endotoxin exposure| balb/c mice| cd14 gene| hay-fever| 1st year| cpg dna| asthma| responses| sensitization.	JUN 1-2004	major peanut allergen| endotoxin exposure| balb/c mice| cd14 gene| hay-fever| 1st year| cpg dna| asthma| responses| sensitization	Bashir, MEH; Louie, S; Shi, HN; Nagler-Anderson, C	Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy		JOURNAL OF IMMUNOLOGY		MAJOR PEANUT ALLERGEN; ENDOTOXIN EXPOSURE; BALB/C MICE; CD14 GENE; HAY-FEVER; 1ST YEAR; CPG DNA; ASTHMA; RESPONSES; SENSITIZATION	The mechanisms by which signaling by the innate immune system controls susceptibility to allergy are poorly understood. In this report, we show that intragastric administration of a food allergen with a mucosal adjuvant induces allergen-specific IgE, elevated plasma histamine levels, and anaphylactic symptoms in three different strains of mice lacking a functional receptor for bacterial LPS (Toll-like receptor 4 (TLR4)), but not in MHC-matched or congenic controls. Susceptibility to allergy correlates with a Th2-biased cytokine response in both the mucosal (mesenteric lymph node and Peyer's patch) and systemic (spleen) tissues of TLR4-mutant or -deficient mice. TLR4-mutant mice are not inherently impaired in their ability to regulate Th1 cytokine production because they respond to stimulation via TLR9. Coadministration of CpG oligodeoxynucleotides during sensitization of TLR4-mutant mice with allergen plus CT abrogates anaphylactic symptoms and Ag-specific IgE, and results in a Th1-polarized cytokine response. When the composition of the bacterial flora is reduced and altered by antibiotic administration (beginning at 2 wk of age), TLR4 wild-type mice become as susceptible to the induction of allergy as their TLR4-mutant counterparts. Both allergen-specific IgE and Th2 cytokine responses are reduced in antibiotic-treated mice in which the flora has been allowed to repopulate. Taken together, our results suggest that TLR4-dependent signals provided by the intestinal commensal flora inhibit the development of allergic responses to food Ags.	38	195	2004	10		Immunology
Urban traffic and pollutant exposure related to respiratory outcomes and atopy in a large sample of children. Conflicting results have been reported for the relationship between traffic exposure and inception of atopy. The effect of traffic on the prevalence of asthma and atopy at school age was investigated in a representative population. Random samples of schoolchildren (n = 7,509, response rate 83.7%,) were studied using the International Study of Asthma and Allergies in Childhood phase-II protocol with skin-prick tests, measurements of specific immunoglobulin E and lung function. Traffic exposure was assessed via traffic counts and by an emission model which predicted soot, benzene and nitrogen dioxide (NO2). Traffic counts were associated with current asthma, wheeze and cough. In children with tobacco-smoke exposure, traffic volume was additionally associated with a positive skin-prick test. Cough was associated with soot, benzene and NO2, current asthma with soot and benzene, and current wheeze with benzene and NO2. No pollutant was associated with allergic sensitisation. High vehicle traffic was associated with asthma, cough and wheeze, and in children additionally exposed to environmental tobacco smoke, with allergic sensitisation. However, effects of socioeconomic factors associated with living close to busy roads cannot be ruled out.. asthma| atopy| children| pollutants| respiratory| traffic|diesel exhaust particles| air-pollution| allergic sensitization| lung-function| asthma| symptoms| prevalence| inflammation| germany| pollen.	JUN-2003	asthma| atopy| children| pollutants| respiratory| traffic|diesel exhaust particles| air-pollution| allergic sensitization| lung-function| asthma| symptoms| prevalence| inflammation| germany| pollen	Nicolai, T; Carr, D; Weiland, SK; Duhme, H; von Ehrenstein, O; Wagner, C; von Mutius, E	Urban traffic and pollutant exposure related to respiratory outcomes and atopy in a large sample of children		EUROPEAN RESPIRATORY JOURNAL	asthma; atopy; children; pollutants; respiratory; traffic	DIESEL EXHAUST PARTICLES; AIR-POLLUTION; ALLERGIC SENSITIZATION; LUNG-FUNCTION; ASTHMA; SYMPTOMS; PREVALENCE; INFLAMMATION; GERMANY; POLLEN	Conflicting results have been reported for the relationship between traffic exposure and inception of atopy. The effect of traffic on the prevalence of asthma and atopy at school age was investigated in a representative population. Random samples of schoolchildren (n = 7,509, response rate 83.7%,) were studied using the International Study of Asthma and Allergies in Childhood phase-II protocol with skin-prick tests, measurements of specific immunoglobulin E and lung function. Traffic exposure was assessed via traffic counts and by an emission model which predicted soot, benzene and nitrogen dioxide (NO2). Traffic counts were associated with current asthma, wheeze and cough. In children with tobacco-smoke exposure, traffic volume was additionally associated with a positive skin-prick test. Cough was associated with soot, benzene and NO2, current asthma with soot and benzene, and current wheeze with benzene and NO2. No pollutant was associated with allergic sensitisation. High vehicle traffic was associated with asthma, cough and wheeze, and in children additionally exposed to environmental tobacco smoke, with allergic sensitisation. However, effects of socioeconomic factors associated with living close to busy roads cannot be ruled out.	31	195	2003	8	10.1183/09031936.03.00041103	Respiratory System
Factors associated with persistent airflow limitation in severe asthma. Persistent airflow limitation can develop in nonsmoking patients with asthma. However, the prevalence and risk factors for airways obstruction with incomplete reversibility in asthma are unknown. We assessed the prevalence of persistent airflow limitation (defined as postbronchodilator FEV1 or FEV1/VC < 75% predicted) in 132 nonsmoking outpatients with severe asthma visiting chest physicians in general hospitals in The Netherlands. They had used inhaled corticosteroids (greater than or equal to 1,600 mug/d) and/or daily oral prednisone and long-acting bronchodilators for > 1 yr. In addition, we examined whether persistent airways obstruction in these patients was associated with specific clinical characteristics (age at onset, smoking history, atopic status, bronchodilator reversibility, provocative concentration of histamine causing a 20% decrease in FEV1 [PC(20)histamine]) or markers of inflammation (exhaled nitric oxide [NO], blood eosinophils, total IgE; and eosinophilia or neutrophilia in induced sputum). Multiple logistic regression analyses were used to calculate adjusted odds ratios (OR). Persistent airflow limitation was observed in 49% of the patients in the study, and apart from older age and longer asthma duration, was strongly associated with a sputum eosinophils percent greater than or equal to 2% (OR = 7.7; confidence interval [CI]: 2.4 to 25), PC(20)histamine less than or equal to 1.0 mg/ml (OR = 3.9; CI: 1.2 to 13), and adult onset (greater than or equal to 18 yr) of asthma (OR = 3.3; CI: 1.2 to 9). Only sputum eosinophilia appeared to be independently associated with persistent airflow limitation (OR = 8.9; CI: 1.3 to 59). In conclusion, persistent airflow limitation is common in adult patients with severe asthma, and is associated with adult onset of the disease, airway hyperresponsiveness, and most importantly, sputum eosinophilia. These findings suggest that eosinophilic airway inflammation contributes to persistent airflow limitation in severe asthma. Whether reduction of sputum eosinophils with more vigorous treatment leads to a better prognosis in severe asthma is still an open question.. asthma| severity of illness index| airway obstruction| sputum| eosinophilia|air-flow obstruction| long-term inflammation| lung-function| bronchial-asthma| follow-up| pulmonary-function| natural-history| risk-factors| decline| adults.	SEP 1-2001	asthma| severity of illness index| airway obstruction| sputum| eosinophilia|air-flow obstruction| long-term inflammation| lung-function| bronchial-asthma| follow-up| pulmonary-function| natural-history| risk-factors| decline| adults	ten Brinke, A; Zwinderman, AH; Sterk, PJ; Rabe, KF; Bel, EH	Factors associated with persistent airflow limitation in severe asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; severity of illness index; airway obstruction; sputum; eosinophilia	AIR-FLOW OBSTRUCTION; LONG-TERM INFLAMMATION; LUNG-FUNCTION; BRONCHIAL-ASTHMA; FOLLOW-UP; PULMONARY-FUNCTION; NATURAL-HISTORY; RISK-FACTORS; DECLINE; ADULTS	Persistent airflow limitation can develop in nonsmoking patients with asthma. However, the prevalence and risk factors for airways obstruction with incomplete reversibility in asthma are unknown. We assessed the prevalence of persistent airflow limitation (defined as postbronchodilator FEV1 or FEV1/VC < 75% predicted) in 132 nonsmoking outpatients with severe asthma visiting chest physicians in general hospitals in The Netherlands. They had used inhaled corticosteroids (greater than or equal to 1,600 mug/d) and/or daily oral prednisone and long-acting bronchodilators for > 1 yr. In addition, we examined whether persistent airways obstruction in these patients was associated with specific clinical characteristics (age at onset, smoking history, atopic status, bronchodilator reversibility, provocative concentration of histamine causing a 20% decrease in FEV1 [PC(20)histamine]) or markers of inflammation (exhaled nitric oxide [NO], blood eosinophils, total IgE; and eosinophilia or neutrophilia in induced sputum). Multiple logistic regression analyses were used to calculate adjusted odds ratios (OR). Persistent airflow limitation was observed in 49% of the patients in the study, and apart from older age and longer asthma duration, was strongly associated with a sputum eosinophils percent greater than or equal to 2% (OR = 7.7; confidence interval [CI]: 2.4 to 25), PC(20)histamine less than or equal to 1.0 mg/ml (OR = 3.9; CI: 1.2 to 13), and adult onset (greater than or equal to 18 yr) of asthma (OR = 3.3; CI: 1.2 to 9). Only sputum eosinophilia appeared to be independently associated with persistent airflow limitation (OR = 8.9; CI: 1.3 to 59). In conclusion, persistent airflow limitation is common in adult patients with severe asthma, and is associated with adult onset of the disease, airway hyperresponsiveness, and most importantly, sputum eosinophilia. These findings suggest that eosinophilic airway inflammation contributes to persistent airflow limitation in severe asthma. Whether reduction of sputum eosinophils with more vigorous treatment leads to a better prognosis in severe asthma is still an open question.	42	195	2001	5		General & Internal Medicine; Respiratory System
Low diversity of the gut microbiota in infants with atopic eczema. Background: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. Objective: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. Methods: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). Results: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P = .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P = .02 and P = .01) and the phylum Proteobacteria at 12 months of age (P = .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R [edgeR] test: P = .008, q = 0.02). Conclusion: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema. (J Allergy Clin Immunol 2012;129:434-40.). allergic disease| bacteroides species| diversity| eczema| hygiene hypothesis| infant| microbiota| molecular microbiology| pyrosequencing| sutterella species|intestinal microbiota| molecular analysis| reduced diversity| microflora| exposure| disease| allergy| cohort| risk.	FEB-2012	allergic disease| bacteroides species| diversity| eczema| hygiene hypothesis| infant| microbiota| molecular microbiology| pyrosequencing| sutterella species|intestinal microbiota| molecular analysis| reduced diversity| microflora| exposure| disease| allergy| cohort| risk	Abrahamsson, TR; Jakobsson, HE; Andersson, AF; Bjorksten, B; Engstrand, L; Jenmalm, MC	Low diversity of the gut microbiota in infants with atopic eczema		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergic disease; Bacteroides species; diversity; eczema; hygiene hypothesis; infant; microbiota; molecular microbiology; pyrosequencing; Sutterella species	INTESTINAL MICROBIOTA; MOLECULAR ANALYSIS; REDUCED DIVERSITY; MICROFLORA; EXPOSURE; DISEASE; ALLERGY; COHORT; RISK	Background: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. Objective: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. Methods: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). Results: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P = .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P = .02 and P = .01) and the phylum Proteobacteria at 12 months of age (P = .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R [edgeR] test: P = .008, q = 0.02). Conclusion: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema. (J Allergy Clin Immunol 2012;129:434-40.)	36	194	2012	9	10.1016/j.jaci.2011.10.025	Allergy; Immunology
Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study. Objective To investigate the importance of sensitisation and exposure to allergens and viral infection in precipitating acute asthma in adults resulting in admission to hospital. Design Case-control study. Setting Large district general hospital. Participants 60 patients aged 17-50 admitted to hospital over a year with acute asthma, matched with two controls: patients with stable asthma recruited from die outpatient department and patients admitted to hospital with non-respiratory conditions (inpatient controls). Main outcome measures Atopic status (skin testing and total and specific IgE), presence of common respiratory Viruses and atypical bacteria (polymerase chain reaction), dust samples from homes, and exposure to allergens (enzyme linked immunosorbent assay (ELISA): Der p 1, Fel d 1, Can f 1, and Bla g 2). Results Viruses were detected in 31 of 177 patients. The difference in the frequency of viruses detected between the groups was significant (admitted with asthma 26%, stable asthma 18%, inpatient controls 9%; P=0.04). A significantly higher proportion of patients admitted with asthma (66%) were sensitised and exposed to either mite, cat, or dog allergen than patients with stable asthma (37%) and inpatient controls (15%; P < 0.001). Being sensitised and exposed to allergens was all independent associate of the group admitted to hospital (odds ratio 2.3, 95% confidence interval 1.0 to 5.4; P=0.05), whereas the combination of sensitisation, high exposure to one or more allergens, and viral detection considerably increased the risk of being admitted with asthma (8.4, 2.1 to 32.8; P=0.002). Conclusions Allergens and viruses may act together to exacerbate asthma.. monoclonal-antibodies| indoor allergens| exposure| children| sensitization| rhinovirus-16| exacerbations| inflammation| purification| infections.	MAR 30-2002	monoclonal-antibodies| indoor allergens| exposure| children| sensitization| rhinovirus-16| exacerbations| inflammation| purification| infections	Green, RM; Cusotvic, A; Sanderson, G; Hunter, J; Johnston, SL; Woodcock, A	Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study		BRITISH MEDICAL JOURNAL		MONOCLONAL-ANTIBODIES; INDOOR ALLERGENS; EXPOSURE; CHILDREN; SENSITIZATION; RHINOVIRUS-16; EXACERBATIONS; INFLAMMATION; PURIFICATION; INFECTIONS	Objective To investigate the importance of sensitisation and exposure to allergens and viral infection in precipitating acute asthma in adults resulting in admission to hospital. Design Case-control study. Setting Large district general hospital. Participants 60 patients aged 17-50 admitted to hospital over a year with acute asthma, matched with two controls: patients with stable asthma recruited from die outpatient department and patients admitted to hospital with non-respiratory conditions (inpatient controls). Main outcome measures Atopic status (skin testing and total and specific IgE), presence of common respiratory Viruses and atypical bacteria (polymerase chain reaction), dust samples from homes, and exposure to allergens (enzyme linked immunosorbent assay (ELISA): Der p 1, Fel d 1, Can f 1, and Bla g 2). Results Viruses were detected in 31 of 177 patients. The difference in the frequency of viruses detected between the groups was significant (admitted with asthma 26%, stable asthma 18%, inpatient controls 9%; P=0.04). A significantly higher proportion of patients admitted with asthma (66%) were sensitised and exposed to either mite, cat, or dog allergen than patients with stable asthma (37%) and inpatient controls (15%; P < 0.001). Being sensitised and exposed to allergens was all independent associate of the group admitted to hospital (odds ratio 2.3, 95% confidence interval 1.0 to 5.4; P=0.05), whereas the combination of sensitisation, high exposure to one or more allergens, and viral detection considerably increased the risk of being admitted with asthma (8.4, 2.1 to 32.8; P=0.002). Conclusions Allergens and viruses may act together to exacerbate asthma.	24	194	2002	7	10.1136/bmj.324.7340.763	General & Internal Medicine
Epidemiological evidence of the effects of ultrafine particle exposure. In epidemiological studies associations have been observed consistently and coherently between ambient concentrations of particulate matter and morbidity and mortality. With improvement of measurement techniques, the effects became clearer when smaller particle sizes were considered. Therefore, it seems worthwhile to look at the smallest size fraction available today, namely ultrafine particles (UPs, diameter below 0.1 mum) and to compare their health effects with those of fine particles (FPs, diameter below 2.5 mum) However, there are only few studies available which allow such a comparison. Four panel studies with asthma patients have been performed in Germany and Finland. A decrease of peak expiratory flow and an increase of daily symptoms and medication use was found for elevated daily particle concentrations, and in three of these studies it was strongest for UPs. One large study on daily mortality is available from Germany. It showed comparable effects of fine and ultrafine particles in all sire classes considered. However, FPs showed more immediate effects while UPs showed more delayed effects with a lag of four days between particulate concentrations and mortality. Furthermore, immediate effects were clearer in respiratory cases, whereas delayed effects were clearer in cardiovascular cases. In total, the limited body of studies suggests that there are health effects, due to both UPs and FPs, which might be independent from each other. If this is confirmed in further investigations, it might have important implications for monitoring and regulation, which until now does not exist for UPs. Data from Germany show that FPs cannot be used as indicator for UPs: the time trends for FPs decreased, while UPs was stable and the smallest size fraction of UPs has continually increased since 1991/92.. ultrafine particles| fine particles| short-term effects| mortality| respiratory diseases| cardiovascular diseases|particulate air-pollution| coronary heart-disease| environmental aerosols| plasma viscosity| daily mortality| children| association| episode| cohort| number.	OCT 15-2000	ultrafine particles| fine particles| short-term effects| mortality| respiratory diseases| cardiovascular diseases|particulate air-pollution| coronary heart-disease| environmental aerosols| plasma viscosity| daily mortality| children| association| episode| cohort| number	Wichmann, HE; Peters, A	Epidemiological evidence of the effects of ultrafine particle exposure		PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES	ultrafine particles; fine particles; short-term effects; mortality; respiratory diseases; cardiovascular diseases	PARTICULATE AIR-POLLUTION; CORONARY HEART-DISEASE; ENVIRONMENTAL AEROSOLS; PLASMA VISCOSITY; DAILY MORTALITY; CHILDREN; ASSOCIATION; EPISODE; COHORT; NUMBER	In epidemiological studies associations have been observed consistently and coherently between ambient concentrations of particulate matter and morbidity and mortality. With improvement of measurement techniques, the effects became clearer when smaller particle sizes were considered. Therefore, it seems worthwhile to look at the smallest size fraction available today, namely ultrafine particles (UPs, diameter below 0.1 mum) and to compare their health effects with those of fine particles (FPs, diameter below 2.5 mum) However, there are only few studies available which allow such a comparison. Four panel studies with asthma patients have been performed in Germany and Finland. A decrease of peak expiratory flow and an increase of daily symptoms and medication use was found for elevated daily particle concentrations, and in three of these studies it was strongest for UPs. One large study on daily mortality is available from Germany. It showed comparable effects of fine and ultrafine particles in all sire classes considered. However, FPs showed more immediate effects while UPs showed more delayed effects with a lag of four days between particulate concentrations and mortality. Furthermore, immediate effects were clearer in respiratory cases, whereas delayed effects were clearer in cardiovascular cases. In total, the limited body of studies suggests that there are health effects, due to both UPs and FPs, which might be independent from each other. If this is confirmed in further investigations, it might have important implications for monitoring and regulation, which until now does not exist for UPs. Data from Germany show that FPs cannot be used as indicator for UPs: the time trends for FPs decreased, while UPs was stable and the smallest size fraction of UPs has continually increased since 1991/92.	52	194	2000	18		Science & Technology - Other Topics
"Environmental biodiversity, human microbiota, and allergy are interrelated. Rapidly declining biodiversity may be a contributing factor to another global megatrend-the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the ""biodiversity hypothesis,"" reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 x 150 km, we show that environmental biodiversity in the surroundings of the study subjects' homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the Gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general.. biodiversity benefits| hygiene hypothesis| microbial deprivation| civilization diseases|blood mononuclear-cells| gram-positive bacteria| in-vitro stimulation| gut microbiota| atopic eczema| intestinal microbiota| hygiene hypothesis| reduced diversity| immune-responses| childhood asthma."	MAY 22-2012	biodiversity benefits| hygiene hypothesis| microbial deprivation| civilization diseases|blood mononuclear-cells| gram-positive bacteria| in-vitro stimulation| gut microbiota| atopic eczema| intestinal microbiota| hygiene hypothesis| reduced diversity| immune-responses| childhood asthma	Hanski, I; von Hertzen, L; Fyhrquist, N; Koskinen, K; Torppa, K; Laatikainen, T; Karisola, P; Auvinen, P; Paulin, L; Makela, MJ; Vartiainen, E; Kosunen, TU; Alenius, H; Haahtela, T	Environmental biodiversity, human microbiota, and allergy are interrelated		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	biodiversity benefits; hygiene hypothesis; microbial deprivation; civilization diseases	BLOOD MONONUCLEAR-CELLS; GRAM-POSITIVE BACTERIA; IN-VITRO STIMULATION; GUT MICROBIOTA; ATOPIC ECZEMA; INTESTINAL MICROBIOTA; HYGIENE HYPOTHESIS; REDUCED DIVERSITY; IMMUNE-RESPONSES; CHILDHOOD ASTHMA	"Rapidly declining biodiversity may be a contributing factor to another global megatrend-the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the ""biodiversity hypothesis,"" reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 x 150 km, we show that environmental biodiversity in the surroundings of the study subjects' homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the Gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general."	53	193	2012	6	10.1073/pnas.1205624109	Science & Technology - Other Topics
Adaptive Foxp3(+) regulatory T cell-dependent and -independent control of allergic inflammation. Adaptive Foxp3(+) regulatory T (Treg) cells develop during induction of mucosal tolerance and after immunization. Large numbers of Foxp3(+) T cells have been found in inflamed tissues. We investigated the role of adaptive Foxp3(+) Treg cells in mucosal tolerance and in chronic allergic lung inflammation. We used two strains of mice that are devoid of naturally occurring Treg cells; one is capable of generating adaptive Foxp3+ Treg cells upon exposure to antigen, whereas the other is deficient in both naturally occurring and adaptive Foxp3(+) Treg cells. We found that adaptive Foxp3(+) Treg cells were essential for establishing mucosal tolerance and for suppressing IL-4 production and lymphoid neogenesis in chronic inflammation, whereas IL-5 production and eosinophilia. could be controlled by Foxp3-independent IFN-gamma-dependent mechanisms. Thus, whereas adaptive Foxp3(+) Treg cells regulate sensitization to allergens and the severity of chronic inflammation, IFN-gamma-producing cells can play a beneficial role in inflammatory conditions involving eosinophils.. spontaneous autoimmune encephalomyelitis| transcription factor foxp3| receptor transgenic mice| myelin basic-protein| tgf-beta| dendritic cells| retinoic-acid| in-vivo| airway hyperresponsiveness| induction.	JUL 18-2008	spontaneous autoimmune encephalomyelitis| transcription factor foxp3| receptor transgenic mice| myelin basic-protein| tgf-beta| dendritic cells| retinoic-acid| in-vivo| airway hyperresponsiveness| induction	de Lafaille, MAC; Kutchukhidze, N; Shen, S; Ding, Y; Yee, H; Lafaille, JJ	Adaptive Foxp3(+) regulatory T cell-dependent and -independent control of allergic inflammation		IMMUNITY		SPONTANEOUS AUTOIMMUNE ENCEPHALOMYELITIS; TRANSCRIPTION FACTOR FOXP3; RECEPTOR TRANSGENIC MICE; MYELIN BASIC-PROTEIN; TGF-BETA; DENDRITIC CELLS; RETINOIC-ACID; IN-VIVO; AIRWAY HYPERRESPONSIVENESS; INDUCTION	Adaptive Foxp3(+) regulatory T (Treg) cells develop during induction of mucosal tolerance and after immunization. Large numbers of Foxp3(+) T cells have been found in inflamed tissues. We investigated the role of adaptive Foxp3(+) Treg cells in mucosal tolerance and in chronic allergic lung inflammation. We used two strains of mice that are devoid of naturally occurring Treg cells; one is capable of generating adaptive Foxp3+ Treg cells upon exposure to antigen, whereas the other is deficient in both naturally occurring and adaptive Foxp3(+) Treg cells. We found that adaptive Foxp3(+) Treg cells were essential for establishing mucosal tolerance and for suppressing IL-4 production and lymphoid neogenesis in chronic inflammation, whereas IL-5 production and eosinophilia. could be controlled by Foxp3-independent IFN-gamma-dependent mechanisms. Thus, whereas adaptive Foxp3(+) Treg cells regulate sensitization to allergens and the severity of chronic inflammation, IFN-gamma-producing cells can play a beneficial role in inflammatory conditions involving eosinophils.	51	193	2008	13	10.1016/j.immuni.2008.05.010	Immunology
Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma. Allergic asthma is a chronic disease characterized by airway obstruction in response to allergen exposure. It results from an inappropriate T helper type 2 response to environmental airborne antigens and affects 300 million individuals(1). Its prevalence has increased markedly in recent decades, most probably as a result of changes in environmental factors(2). Exposure to environmental antigens during infancy is crucial to the development of asthma(3). Epidemiological studies on the relationship between breastfeeding and allergic diseases have reached conflicting results(4-8). Here, we have investigated whether the exposure of lactating mice to an airborne allergen affects asthma development in progeny. We found that airborne antigens were efficiently transferred from the mother to the neonate through milk and that tolerance induction did not require the transfer of immunoglobulins. Breastfeeding-induced tolerance relied on the presence of transforming growth factor (TGF)-beta during lactation, was mediated by regulatory CD4(+) T lymphocytes and depended on TGF-beta signaling in T cells. In conclusion, breast milk-mediated transfer of an antigen to the neonate resulted in oral tolerance induction leading to antigen-specific protection from allergic airway disease. This study may pave the way for the design of new strategies to prevent the development of allergic diseases.. growth-factor-beta| experimental autoimmune encephalomyelitis| t-cells| immune-responses| inhaled antigen| oral tolerance| mice| protein| absorption| expression.	FEB-2008	growth-factor-beta| experimental autoimmune encephalomyelitis| t-cells| immune-responses| inhaled antigen| oral tolerance| mice| protein| absorption| expression	Verhasselt, V; Milcent, V; Cazareth, J; Kanda, A; Fleury, S; Dombrowicz, D; Glaichenhaus, N; Julia, V	Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma		NATURE MEDICINE		GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELLS; IMMUNE-RESPONSES; INHALED ANTIGEN; ORAL TOLERANCE; MICE; PROTEIN; ABSORPTION; EXPRESSION	Allergic asthma is a chronic disease characterized by airway obstruction in response to allergen exposure. It results from an inappropriate T helper type 2 response to environmental airborne antigens and affects 300 million individuals(1). Its prevalence has increased markedly in recent decades, most probably as a result of changes in environmental factors(2). Exposure to environmental antigens during infancy is crucial to the development of asthma(3). Epidemiological studies on the relationship between breastfeeding and allergic diseases have reached conflicting results(4-8). Here, we have investigated whether the exposure of lactating mice to an airborne allergen affects asthma development in progeny. We found that airborne antigens were efficiently transferred from the mother to the neonate through milk and that tolerance induction did not require the transfer of immunoglobulins. Breastfeeding-induced tolerance relied on the presence of transforming growth factor (TGF)-beta during lactation, was mediated by regulatory CD4(+) T lymphocytes and depended on TGF-beta signaling in T cells. In conclusion, breast milk-mediated transfer of an antigen to the neonate resulted in oral tolerance induction leading to antigen-specific protection from allergic airway disease. This study may pave the way for the design of new strategies to prevent the development of allergic diseases.	30	193	2008	6	10.1038/nm1718	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Immune mechanisms of allergen-specific sublingual immunotherapy. Sublingual immunotherapy has been shown in some clinical studies to modulate allergen-specific antibody responses [with a decrease in the immunoglobulin E/immunoglobulin G4 (IgE/IgG4) ratio] and to reduce the recruitment and activation of proinflammatory cells in target mucosa. Whereas a central paradigm for successful immunotherapy has been to reorient the pattern of allergen-specific T-cell responses in atopic patients from a T helper (Th)2 to Th1 profile, there is currently a growing interest in eliciting regulatory T cells, capable of downregulating both Th1 and Th2 responses through the production of interleukin (IL)-10 and/or transforming growth factor (TGF)-beta. We discuss herein immune mechanisms involved during allergen-specific sublingual immunotherapy (SLIT), in comparison with subcutaneous immunotherapy. During SLIT, the allergen is captured within the oral mucosa by Langerhans-like dendritic cells expressing high-affinity IgE receptors, producing IL-10 and TGF-beta, and upregulating indoleamine dioxygenase (IDO), suggesting that such cells are prone to induce tolerance. The oral mucosa contains limited number of proinflammatory cells, such as mast cells, thereby explaining the well-established safety profile of SLIT. In this context, second-generation vaccines based on recombinant allergens in a native conformation formulated with adjuvants are designed to target Langerhans-like cells in the sublingual mucosa, with the aim to induce allergen-specific regulatory T cells. Importantly, such recombinant vaccines should facilitate the identification of biological markers of SLIT efficacy in humans.. allergy vaccine| langerhans cells| regulatory t lymphocyte| sublingual immunotherapy|grass-pollen immunotherapy| regulatory t-cells| randomized controlled-trial| house-dust mites| placebo-controlled evaluation| messenger-rna expression| blocking igg antibodies| double-blind| dendritic cells| hay-fever.	FEB-2006	allergy vaccine| langerhans cells| regulatory t lymphocyte| sublingual immunotherapy|grass-pollen immunotherapy| regulatory t-cells| randomized controlled-trial| house-dust mites| placebo-controlled evaluation| messenger-rna expression| blocking igg antibodies| double-blind| dendritic cells| hay-fever	Moingeon, P; Batard, T; Fadel, R; Frati, F; Sieber, J; Van Overtvelt, L	Immune mechanisms of allergen-specific sublingual immunotherapy		ALLERGY	allergy vaccine; Langerhans cells; regulatory T lymphocyte; sublingual immunotherapy	GRASS-POLLEN IMMUNOTHERAPY; REGULATORY T-CELLS; RANDOMIZED CONTROLLED-TRIAL; HOUSE-DUST MITES; PLACEBO-CONTROLLED EVALUATION; MESSENGER-RNA EXPRESSION; BLOCKING IGG ANTIBODIES; DOUBLE-BLIND; DENDRITIC CELLS; HAY-FEVER	Sublingual immunotherapy has been shown in some clinical studies to modulate allergen-specific antibody responses [with a decrease in the immunoglobulin E/immunoglobulin G4 (IgE/IgG4) ratio] and to reduce the recruitment and activation of proinflammatory cells in target mucosa. Whereas a central paradigm for successful immunotherapy has been to reorient the pattern of allergen-specific T-cell responses in atopic patients from a T helper (Th)2 to Th1 profile, there is currently a growing interest in eliciting regulatory T cells, capable of downregulating both Th1 and Th2 responses through the production of interleukin (IL)-10 and/or transforming growth factor (TGF)-beta. We discuss herein immune mechanisms involved during allergen-specific sublingual immunotherapy (SLIT), in comparison with subcutaneous immunotherapy. During SLIT, the allergen is captured within the oral mucosa by Langerhans-like dendritic cells expressing high-affinity IgE receptors, producing IL-10 and TGF-beta, and upregulating indoleamine dioxygenase (IDO), suggesting that such cells are prone to induce tolerance. The oral mucosa contains limited number of proinflammatory cells, such as mast cells, thereby explaining the well-established safety profile of SLIT. In this context, second-generation vaccines based on recombinant allergens in a native conformation formulated with adjuvants are designed to target Langerhans-like cells in the sublingual mucosa, with the aim to induce allergen-specific regulatory T cells. Importantly, such recombinant vaccines should facilitate the identification of biological markers of SLIT efficacy in humans.	148	193	2006	15	10.1111/j.1398-9995.2006.01002.x	Allergy; Immunology
Allergy or tolerance in children sensitized to peanut: Prevalence and differentiation using component-resolved diagnostics. Background: Not all peanut-sensitized children develop allergic reactions on exposure. Objective: To establish by oral food challenge the proportion of children with clinical peanut allergy among those considered peanut-sensitized by using skin prick tests and/or IgE measurement, and to investigate whether component-resolved diagnostics using microarray could differentiate peanut allergy from tolerance. Methods: Within a population-based birth cohort, we ascertained peanut sensitization by skin tests and IgE measurement at age 8 years. Among sensitized children, we determined peanut allergy versus tolerance by oral food challenges. We used open challenge among children consuming peanuts (n = 45); others underwent double-blind placebo-controlled challenge (n = 34). We compared sensitization profiles between children with peanut allergy and peanut-tolerant children by using a microarray with 12 pure components (major peanut and potentially cross-reactive components, including grass allergens). Results: Of 933 children, 110 (11.8%) were peanut-sensitized. Nineteen were not challenged (17 no consent). Twelve with a convincing history of reactions on exposure, IgE >= 15 kUA/L and/or skin test >= 8mm were considered allergic without challenge. Of the remaining 79 children who underwent challenge, 7 had >= 2 objective signs and were designated as having peanut allergy. We estimated the prevalence of clinical peanut allergy among sensitized subjects as 22.4% (95% CI, 14.8% to 32.3%). By using component-resolved diagnostics, we detected marked differences in the pattern of component recognition between children with peanut allergy (n = 29; group enriched with 12 children with allergy) and peanut-tolerant children (n = 52). The peanut component Ara h 2 was the most important predictor of clinical allergy. Conclusion: The majority of children considered peanut-sensitized on the basis of standard tests do not have peanut allergy. Component-resolved diagnostics may facilitate the diagnosis of peanut allergy. Q Allergy Clin Immunol 2010;125:191-7.). peanut allergy| oral food challenge| component-resolved diagnostics| ara h 2| microarray| birth cohort|food challenges| recombinant allergens| skin prick| ige| pollen| identification| association| adolescents| dermatitis| reactivity.	JAN-2010	peanut allergy| oral food challenge| component-resolved diagnostics| ara h 2| microarray| birth cohort|food challenges| recombinant allergens| skin prick| ige| pollen| identification| association| adolescents| dermatitis| reactivity	Nicolaou, N; Poorafshar, M; Murray, C; Simpson, A; Winell, H; Kerry, G; Harlin, A; Woodcock, A; Ahlstedt, S; Custovic, A	Allergy or tolerance in children sensitized to peanut: Prevalence and differentiation using component-resolved diagnostics		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Peanut allergy; oral food challenge; component-resolved diagnostics; Ara h 2; microarray; birth cohort	FOOD CHALLENGES; RECOMBINANT ALLERGENS; SKIN PRICK; IGE; POLLEN; IDENTIFICATION; ASSOCIATION; ADOLESCENTS; DERMATITIS; REACTIVITY	Background: Not all peanut-sensitized children develop allergic reactions on exposure. Objective: To establish by oral food challenge the proportion of children with clinical peanut allergy among those considered peanut-sensitized by using skin prick tests and/or IgE measurement, and to investigate whether component-resolved diagnostics using microarray could differentiate peanut allergy from tolerance. Methods: Within a population-based birth cohort, we ascertained peanut sensitization by skin tests and IgE measurement at age 8 years. Among sensitized children, we determined peanut allergy versus tolerance by oral food challenges. We used open challenge among children consuming peanuts (n = 45); others underwent double-blind placebo-controlled challenge (n = 34). We compared sensitization profiles between children with peanut allergy and peanut-tolerant children by using a microarray with 12 pure components (major peanut and potentially cross-reactive components, including grass allergens). Results: Of 933 children, 110 (11.8%) were peanut-sensitized. Nineteen were not challenged (17 no consent). Twelve with a convincing history of reactions on exposure, IgE >= 15 kUA/L and/or skin test >= 8mm were considered allergic without challenge. Of the remaining 79 children who underwent challenge, 7 had >= 2 objective signs and were designated as having peanut allergy. We estimated the prevalence of clinical peanut allergy among sensitized subjects as 22.4% (95% CI, 14.8% to 32.3%). By using component-resolved diagnostics, we detected marked differences in the pattern of component recognition between children with peanut allergy (n = 29; group enriched with 12 children with allergy) and peanut-tolerant children (n = 52). The peanut component Ara h 2 was the most important predictor of clinical allergy. Conclusion: The majority of children considered peanut-sensitized on the basis of standard tests do not have peanut allergy. Component-resolved diagnostics may facilitate the diagnosis of peanut allergy. Q Allergy Clin Immunol 2010;125:191-7.)	41	192	2010	7	10.1016/j.jaci.2009.10.008	Allergy; Immunology
Atopic Dermatitis. Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2-deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information. (Ann Dermatol 22(2) 125 similar to 137, 2010). atopic dermatitis| pathophysiology| proactive management| therapy|topical calcineurin inhibitors| randomized controlled-trial| innate immune-response| single nucleotide polymorphisms| regulatory t-cells| antimicrobial peptides| allergic inflammation| filaggrin mutations| cytokine milieu| vaccinia virus.	MAY-2010	atopic dermatitis| pathophysiology| proactive management| therapy|topical calcineurin inhibitors| randomized controlled-trial| innate immune-response| single nucleotide polymorphisms| regulatory t-cells| antimicrobial peptides| allergic inflammation| filaggrin mutations| cytokine milieu| vaccinia virus	Bieber, T	Atopic Dermatitis		ANNALS OF DERMATOLOGY	Atopic dermatitis; Pathophysiology; Proactive management; Therapy	TOPICAL CALCINEURIN INHIBITORS; RANDOMIZED CONTROLLED-TRIAL; INNATE IMMUNE-RESPONSE; SINGLE NUCLEOTIDE POLYMORPHISMS; REGULATORY T-CELLS; ANTIMICROBIAL PEPTIDES; ALLERGIC INFLAMMATION; FILAGGRIN MUTATIONS; CYTOKINE MILIEU; VACCINIA VIRUS	Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2-deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information. (Ann Dermatol 22(2) 125 similar to 137, 2010)	106	191	2010	13	10.5021/ad.2010.22.2.125	Dermatology
Traffic-related Air Pollution and the Development of Asthma and Allergies during the First 8 Years of Life. Rationale The role of air pollution exposure in the development of asthma, allergies, and related symptoms remains unclear, due in part to the limited number of prospective cohort studies with sufficiently long follow-ups addressing this problem. Objectives: We studied the association between traffic-related air pollution and the development of asthma, allergy, and related symptoms in a prospective birth cohort study with a unique 8-year follow-up. Methods: Annual questionnaire reports of asthma, hay fever, and related symptoms during the first 8 years of life were analyzed for 3,863 children. At age 8, measurements of allergic sensitization and bronchial hyperresponsiveness were performed for subpopulations (n = 1,700 and 936, respectively). Individual exposures to nitrogen dioxide (NO(2)), particulate matter (PM(2.5)), and soot at the birth address were estimated by land-use regression models. Associations between exposure to traffic-related air pollution and repeated measures of health outcomes were assessed by repeated-measures logistic regression analysis. Effects are presented for an interquartile range increase in exposure after adjusting for covariates. Measurements and Main Results: Annual prevalence was 3 to 6% for asthma and 12 to 23% for asthma symptoms. Annual incidence of asthma was 6% at age 1, and 1 to 2% at later ages. PM2.5 levels were associated with a significant increase in incidence of asthma (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.10-1.49), prevalence of asthma (OR, 1.26; 95% CI, 1.04-1.51), and prevalence of asthma symptoms (OR, 1.15; 95% CI, 1.02-1.28). Findings were similar for NO(2) and soot. Associations were stronger for children who had not moved since birth. Positive associations with hay fever were found in nonmovers only. No associations were found with atopic eczema, allergic sensitization, and bronchial hyperresponsiveness. Conclusions: Exposure to traffic-related air pollution may cause asthma in children.. asthma| allergy| air pollution| cohort| traffic|birth cohort| exposure| childhood| children| symptoms| sensitization| pollutants| infections| infants| models.	MAR 15-2010	asthma| allergy| air pollution| cohort| traffic|birth cohort| exposure| childhood| children| symptoms| sensitization| pollutants| infections| infants| models	Gehring, U; Wijga, AH; Brauer, M; Fischer, P; de Jongste, JC; Kerkhof, M; Oldenwening, M; Smit, HA; Brunekreef, B	Traffic-related Air Pollution and the Development of Asthma and Allergies during the First 8 Years of Life		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; allergy; air pollution; cohort; traffic	BIRTH COHORT; EXPOSURE; CHILDHOOD; CHILDREN; SYMPTOMS; SENSITIZATION; POLLUTANTS; INFECTIONS; INFANTS; MODELS	Rationale The role of air pollution exposure in the development of asthma, allergies, and related symptoms remains unclear, due in part to the limited number of prospective cohort studies with sufficiently long follow-ups addressing this problem. Objectives: We studied the association between traffic-related air pollution and the development of asthma, allergy, and related symptoms in a prospective birth cohort study with a unique 8-year follow-up. Methods: Annual questionnaire reports of asthma, hay fever, and related symptoms during the first 8 years of life were analyzed for 3,863 children. At age 8, measurements of allergic sensitization and bronchial hyperresponsiveness were performed for subpopulations (n = 1,700 and 936, respectively). Individual exposures to nitrogen dioxide (NO(2)), particulate matter (PM(2.5)), and soot at the birth address were estimated by land-use regression models. Associations between exposure to traffic-related air pollution and repeated measures of health outcomes were assessed by repeated-measures logistic regression analysis. Effects are presented for an interquartile range increase in exposure after adjusting for covariates. Measurements and Main Results: Annual prevalence was 3 to 6% for asthma and 12 to 23% for asthma symptoms. Annual incidence of asthma was 6% at age 1, and 1 to 2% at later ages. PM2.5 levels were associated with a significant increase in incidence of asthma (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.10-1.49), prevalence of asthma (OR, 1.26; 95% CI, 1.04-1.51), and prevalence of asthma symptoms (OR, 1.15; 95% CI, 1.02-1.28). Findings were similar for NO(2) and soot. Associations were stronger for children who had not moved since birth. Positive associations with hay fever were found in nonmovers only. No associations were found with atopic eczema, allergic sensitization, and bronchial hyperresponsiveness. Conclusions: Exposure to traffic-related air pollution may cause asthma in children.	29	191	2010	8	10.1164/rccm.200906-0858OC	General & Internal Medicine; Respiratory System
Sex and the Human Placenta: Mediating Differential Strategies of Fetal Growth and Survival. There are known sex specific differences in fetal and neonatal morbidity and mortality. There are also known differences in birthweight centile with males generally being larger than females at birth. These differences are generally ignored when studying obstetric complications of pregnancy and the mechanisms that confer these differences between the sexes are unknown. Current evidence suggests sex specific adaptation of the placenta may be central to the differences in fetal growth and survival. Our research examining pregnancies complicated by asthma has reported sexually dimorphic differences in fetal growth and survival with males adapting placental function to allow for continued growth in an adverse maternal environment while females reduce growth in an attempt to survive further maternal insults. We have reported sex differences in placental cytokine expression, insulin-like growth factor pathways and the placental response to cortisol in relation to the complication of asthma during pregnancy. More recently we have identified sex specific alterations in placental function in pregnancies complicated by preterm delivery which were associated with neonatal outcome and survival. We propose the sexually dimorphic differences in growth and survival of the fetus are mediated by the sex specific function of the human placenta. This review will present evidence supporting this hypothesis and will argue that to ignore the sex of the placenta is no longer sound scientific practice. (C) 2010 Published by IFPA and Elsevier Ltd.. placenta sex| pregnancy| birthweight|maternal asthma| x-inactivation| factor-i| glucocorticoid exposure| antenatal betamethasone| prenatal-diagnosis| androgen receptor| immune-responses| blood-pressure| expression.	MAR-2010	placenta sex| pregnancy| birthweight|maternal asthma| x-inactivation| factor-i| glucocorticoid exposure| antenatal betamethasone| prenatal-diagnosis| androgen receptor| immune-responses| blood-pressure| expression	Clifton, VL	Sex and the Human Placenta: Mediating Differential Strategies of Fetal Growth and Survival		PLACENTA	Placenta Sex; Pregnancy; Birthweight	MATERNAL ASTHMA; X-INACTIVATION; FACTOR-I; GLUCOCORTICOID EXPOSURE; ANTENATAL BETAMETHASONE; PRENATAL-DIAGNOSIS; ANDROGEN RECEPTOR; IMMUNE-RESPONSES; BLOOD-PRESSURE; EXPRESSION	There are known sex specific differences in fetal and neonatal morbidity and mortality. There are also known differences in birthweight centile with males generally being larger than females at birth. These differences are generally ignored when studying obstetric complications of pregnancy and the mechanisms that confer these differences between the sexes are unknown. Current evidence suggests sex specific adaptation of the placenta may be central to the differences in fetal growth and survival. Our research examining pregnancies complicated by asthma has reported sexually dimorphic differences in fetal growth and survival with males adapting placental function to allow for continued growth in an adverse maternal environment while females reduce growth in an attempt to survive further maternal insults. We have reported sex differences in placental cytokine expression, insulin-like growth factor pathways and the placental response to cortisol in relation to the complication of asthma during pregnancy. More recently we have identified sex specific alterations in placental function in pregnancies complicated by preterm delivery which were associated with neonatal outcome and survival. We propose the sexually dimorphic differences in growth and survival of the fetus are mediated by the sex specific function of the human placenta. This review will present evidence supporting this hypothesis and will argue that to ignore the sex of the placenta is no longer sound scientific practice. (C) 2010 Published by IFPA and Elsevier Ltd.	65	191	2010	7	10.1016/j.placenta.2009.11.010	Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
"Exhaled nitric oxide - A predictor of steroid response. Rationale: The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a ""trial of steroid"" to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements. Objectives: We aimed to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, placebo-controlled trial of inhaled fluticasone for 4 weeks. Methods: Comparisons of predictive accuracy were made between FENO, and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. ""Steroid response"" was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosin,e based on established guidelines and recommendations. Results: Steroid response was significantly greater in the highest FENO tertile (> 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb. Conclusions: FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled antiinflammatory therapy.. asthma| exhaled nitric oxide| inhaled corticosteroid| symptoms| treatment response|air-flow obstruction| inhaled corticosteroids| pulmonary-disease| mild asthma| responsiveness| inflammation| children| adults| prednisolone| eosinophils."	AUG 15-2005	asthma| exhaled nitric oxide| inhaled corticosteroid| symptoms| treatment response|air-flow obstruction| inhaled corticosteroids| pulmonary-disease| mild asthma| responsiveness| inflammation| children| adults| prednisolone| eosinophils	Smith, AD; Cowan, JO; Brassett, KP; Filsell, S; McLachlan, C; Monti-Sheehan, G; Herbison, GP; Taylor, DR	Exhaled nitric oxide - A predictor of steroid response		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; exhaled nitric oxide; inhaled corticosteroid; symptoms; treatment response	AIR-FLOW OBSTRUCTION; INHALED CORTICOSTEROIDS; PULMONARY-DISEASE; MILD ASTHMA; RESPONSIVENESS; INFLAMMATION; CHILDREN; ADULTS; PREDNISOLONE; EOSINOPHILS	"Rationale: The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a ""trial of steroid"" to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements. Objectives: We aimed to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, placebo-controlled trial of inhaled fluticasone for 4 weeks. Methods: Comparisons of predictive accuracy were made between FENO, and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. ""Steroid response"" was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosin,e based on established guidelines and recommendations. Results: Steroid response was significantly greater in the highest FENO tertile (> 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb. Conclusions: FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled antiinflammatory therapy."	29	191	2005	7	10.1164/rccm.200411-1498OC	General & Internal Medicine; Respiratory System
Noninjection routes for immunotherapy. Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The traditional subcutaneous route is burdened with the risk of severe adverse events; therefore, safer routes of administration (noninjection or local routes) have been investigated and developed. Controlled trials failed to demonstrate the clinical efficacy and the safety of oral and bronchial administration, and these routes have been abandoned. Local nasal immunotherapy proved effective and safe in 17 of 18 controlled trials; thus it is considered a viable route of immunotherapy. Nevertheless, nasal immunotherapy is effective in rhinitis only and requires a particular administration technique; therefore its use is slowly declining. The sublingual route is supported by numerous controlled trials showing its efficacy in asthma and rhinitis in adults and children. The safety profile, assessed in clinical trials and postmarketing surveillance studies, is satisfactory; the most frequent side effects are gastrointestinal complaints, which can be easily managed by proper dose adjusting. Sublingual immunotherapy is now accepted by the World Health Organization as a valid alternative to the subcutaneous route also in children. Although the long-lasting efficacy has been recently documented for the sublingual route, several points still need to be elucidated, including mechanisms of action, optimal dosage, cost-effectiveness, and adherence.. allergen immunotherapy| sublingual immunotherapy| local nasal immunotherapy| noninjection routes|local nasal immunotherapy| sublingual-swallow immunotherapy| placebo-controlled trial| double-blind placebo| house-dust-mite| allergen-specific immunotherapy| grass-pollen immunotherapy| short ragweed extract| cd4(+) t-cells| preseasonal intranasal immunotherapy.	MAR-2003	allergen immunotherapy| sublingual immunotherapy| local nasal immunotherapy| noninjection routes|local nasal immunotherapy| sublingual-swallow immunotherapy| placebo-controlled trial| double-blind placebo| house-dust-mite| allergen-specific immunotherapy| grass-pollen immunotherapy| short ragweed extract| cd4(+) t-cells| preseasonal intranasal immunotherapy	Canonica, GW; Passalacqua, G	Noninjection routes for immunotherapy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen immunotherapy; sublingual immunotherapy; local nasal immunotherapy; noninjection routes	LOCAL NASAL IMMUNOTHERAPY; SUBLINGUAL-SWALLOW IMMUNOTHERAPY; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND PLACEBO; HOUSE-DUST-MITE; ALLERGEN-SPECIFIC IMMUNOTHERAPY; GRASS-POLLEN IMMUNOTHERAPY; SHORT RAGWEED EXTRACT; CD4(+) T-CELLS; PRESEASONAL INTRANASAL IMMUNOTHERAPY	Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The traditional subcutaneous route is burdened with the risk of severe adverse events; therefore, safer routes of administration (noninjection or local routes) have been investigated and developed. Controlled trials failed to demonstrate the clinical efficacy and the safety of oral and bronchial administration, and these routes have been abandoned. Local nasal immunotherapy proved effective and safe in 17 of 18 controlled trials; thus it is considered a viable route of immunotherapy. Nevertheless, nasal immunotherapy is effective in rhinitis only and requires a particular administration technique; therefore its use is slowly declining. The sublingual route is supported by numerous controlled trials showing its efficacy in asthma and rhinitis in adults and children. The safety profile, assessed in clinical trials and postmarketing surveillance studies, is satisfactory; the most frequent side effects are gastrointestinal complaints, which can be easily managed by proper dose adjusting. Sublingual immunotherapy is now accepted by the World Health Organization as a valid alternative to the subcutaneous route also in children. Although the long-lasting efficacy has been recently documented for the sublingual route, several points still need to be elucidated, including mechanisms of action, optimal dosage, cost-effectiveness, and adherence.	137	191	2003	12	10.1067/mai.2003.129	Allergy; Immunology
Expression of CD14 and Toll-like receptor 2 in farmers' and nonfarmers' children. Children of farmers are at decreased risk of developing allergies. Results of epidemiological studies suggest increased exposure to microbial compounds might be responsible for this reduced risk. Alterations in adaptive immune response are thought to be the underlying mechanism. We measured expression of receptors for microbial compounds known to trigger the innate immune response. We showed that blood cells from farmers' children express significantly higher amounts of CD14 (0.96 vs 0.43, p = 0.0013), and Toll-like receptor 2 (0.11 vs 0.04, p < 0.0001) than those from nonfarmers' children. We propose that the innate immune system responds to the microbial burden in the environment and modulates the development of allergic disease.. asthma.	AUG 10-2002	asthma	Lauener, RP; Birchler, T; Adamski, J; Braun-Fahrlander, C; Bufe, A; Herz, U; von Mutius, E; Nowak, D; Riedler, J; Waser, M; Sennhauser, FH	Expression of CD14 and Toll-like receptor 2 in farmers' and nonfarmers' children		LANCET		ASTHMA	Children of farmers are at decreased risk of developing allergies. Results of epidemiological studies suggest increased exposure to microbial compounds might be responsible for this reduced risk. Alterations in adaptive immune response are thought to be the underlying mechanism. We measured expression of receptors for microbial compounds known to trigger the innate immune response. We showed that blood cells from farmers' children express significantly higher amounts of CD14 (0.96 vs 0.43, p = 0.0013), and Toll-like receptor 2 (0.11 vs 0.04, p < 0.0001) than those from nonfarmers' children. We propose that the innate immune system responds to the microbial burden in the environment and modulates the development of allergic disease.	5	191	2002	2	10.1016/S0140-6736(02)09641-1	General & Internal Medicine
"Assessment of intake from the diet. Exposure assessment is one of the key parts of the risk assessment process. Only intake of toxicologically significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of chemicals in foods this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets, including its fate during the processes within the food production chains 60 how to determine the consumption patterns of the individual foods containing the relevant chemicals, (iii) how to integrate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. The techniques used for the evaluation of these three aspects have been critically reviewed in this paper to determine those areas where the current approaches provide a solid basis for assessments and those areas here improvements are needed or desirable. For those latter areas, options for improvements are being suggested, including. for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food chemicals, harmonisation of food consumption survey methods with the option of a regular pan-European survey, evaluation of probabilistic models and the development of models to assess exposure to food allergens. In all three areas, the limitations of the approaches currently used lead to uncertainties which can either cause an over- or underestimation of real intakes and thus risks, Given these imprecisions, risk assessors tend to build in additional uncertainty factors to avoid health-relevant underestimates. This is partly done by using screening methods designed to look for ""worst case"" situations. Such worse case assumptions lead to intake estimates that are higher than reality. These screening methods are used to screen all those chemicals with a safe intake distribution. For chemicals with a potential risk, more information is needed to allow more refined screening or even the most accurate estimation. More information and more refined methods however. require more resources. The ultimate aims are: (1) to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general: (2) to assess the consumption patterns for the foods containing these Substances, including especially those parts of the population with high consumption and thus potentially high intakes: and (3) to develop and apply tools to predict reliably the likelihood of high end consumption with the presence of high levels of the relevant substances, It has thus been demonstrated that a tiered approach at all three steps can be helpful to optimise the use of the available resources: if relatively crude tools - designed to provide a ""worst case"" estimate - do not suggest a toxicologically significant exposure (or a relevant deficit of a particular nutrient) it may not be necessary to use more sophisticated tools. These ill be needed if initially high intakes are indicated for at least parts of the Population, Existing pragmatic approaches are a first crude step to model food chemical intake. It is recommended to extend. refine and validate this approach in the near future. This has to result in a cost-effective exposure assessment system to be used for existing and potential categories of chemicals. This system of knowledge (with information on sensitivities. accuracy, etc.) will guide future data collection. (C) 2002 ILSL Published by Elsevier Science Ltd All rights reserved.. exposure assessments| risk assessment| food consumption| concentration of chemicals in food| probabilistic modelling|subcutaneous adipose-tissue| term exposure distributions| veterinary drug residues| health-risk assessment| habitual food-intake| nutrient intake| fatty-acids| human-urine| vitamin-e| plasma-concentrations."	FEB-MAR-2002	exposure assessments| risk assessment| food consumption| concentration of chemicals in food| probabilistic modelling|subcutaneous adipose-tissue| term exposure distributions| veterinary drug residues| health-risk assessment| habitual food-intake| nutrient intake| fatty-acids| human-urine| vitamin-e| plasma-concentrations	Kroes, R; Muller, D; Lambe, J; Lowik, MRH; van Klaveren, J; Kleiner, J; Massey, R; Mayer, S; Urieta, I; Verger, P; Visconti, A	Assessment of intake from the diet		FOOD AND CHEMICAL TOXICOLOGY	exposure assessments; risk assessment; food consumption; concentration of chemicals in food; probabilistic modelling	SUBCUTANEOUS ADIPOSE-TISSUE; TERM EXPOSURE DISTRIBUTIONS; VETERINARY DRUG RESIDUES; HEALTH-RISK ASSESSMENT; HABITUAL FOOD-INTAKE; NUTRIENT INTAKE; FATTY-ACIDS; HUMAN-URINE; VITAMIN-E; PLASMA-CONCENTRATIONS	"Exposure assessment is one of the key parts of the risk assessment process. Only intake of toxicologically significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of chemicals in foods this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets, including its fate during the processes within the food production chains 60 how to determine the consumption patterns of the individual foods containing the relevant chemicals, (iii) how to integrate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. The techniques used for the evaluation of these three aspects have been critically reviewed in this paper to determine those areas where the current approaches provide a solid basis for assessments and those areas here improvements are needed or desirable. For those latter areas, options for improvements are being suggested, including. for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food chemicals, harmonisation of food consumption survey methods with the option of a regular pan-European survey, evaluation of probabilistic models and the development of models to assess exposure to food allergens. In all three areas, the limitations of the approaches currently used lead to uncertainties which can either cause an over- or underestimation of real intakes and thus risks, Given these imprecisions, risk assessors tend to build in additional uncertainty factors to avoid health-relevant underestimates. This is partly done by using screening methods designed to look for ""worst case"" situations. Such worse case assumptions lead to intake estimates that are higher than reality. These screening methods are used to screen all those chemicals with a safe intake distribution. For chemicals with a potential risk, more information is needed to allow more refined screening or even the most accurate estimation. More information and more refined methods however. require more resources. The ultimate aims are: (1) to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general: (2) to assess the consumption patterns for the foods containing these Substances, including especially those parts of the population with high consumption and thus potentially high intakes: and (3) to develop and apply tools to predict reliably the likelihood of high end consumption with the presence of high levels of the relevant substances, It has thus been demonstrated that a tiered approach at all three steps can be helpful to optimise the use of the available resources: if relatively crude tools - designed to provide a ""worst case"" estimate - do not suggest a toxicologically significant exposure (or a relevant deficit of a particular nutrient) it may not be necessary to use more sophisticated tools. These ill be needed if initially high intakes are indicated for at least parts of the Population, Existing pragmatic approaches are a first crude step to model food chemical intake. It is recommended to extend. refine and validate this approach in the near future. This has to result in a cost-effective exposure assessment system to be used for existing and potential categories of chemicals. This system of knowledge (with information on sensitivities. accuracy, etc.) will guide future data collection. (C) 2002 ILSL Published by Elsevier Science Ltd All rights reserved."	197	191	2002	59	10.1016/S0278-6915(01)00113-2	Food Science & Technology; Toxicology
Prenatal and Passive Smoke Exposure and Incidence of Asthma and Wheeze: Systematic Review and Meta-analysis. OBJECTIVES: Exposure to passive smoke is a common and avoidable risk factor for wheeze and asthma in children. Substantial growth in the prospective cohort study evidence base provides an opportunity to generate new and more detailed estimates of the magnitude of the effect. A systematic review and meta-analysis was conducted to provide estimates of the prospective effect of smoking by parents or household members on the risk of wheeze and asthma at different stages of childhood. METHODS: We systematically searched Medline, Embase, and conference abstracts to identify cohort studies of the incidence of asthma or wheeze in relation to exposure to prenatal or postnatal maternal, paternal, or household smoking in subjects aged up to 18 years old. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by using random effects model. RESULTS: We identified 79 prospective studies. Exposure to pre-or postnatal passive smoke exposure was associated with a 30% to 70% increased risk of incident wheezing (strongest effect from postnatal maternal smoking on wheeze in children aged <= 2 years, OR = 1.70, 95% CI = 1.24-2.35, 4 studies) and a 21% to 85% increase in incident asthma (strongest effect from prenatal maternal smoking on asthma in children aged <= 2 years, OR = 1.85, 95% CI = 1.35-2.53, 5 studies). CONCLUSIONS: Building upon previous findings, exposure to passive smoking increases the incidence of wheeze and asthma in children and young people by at least 20%. Preventing parental smoking is crucially important to the prevention of asthma. Pediatrics 2012;129:735-744. asthma| wheeze| passive smoking exposure| meta-analysis|prospective birth cohort| environmental tobacco-smoke| body-mass index| maternal smoking| early-childhood| risk-factors| parental smoking| 1st year| atopic-dermatitis| socioeconomic-status.	APR-2012	asthma| wheeze| passive smoking exposure| meta-analysis|prospective birth cohort| environmental tobacco-smoke| body-mass index| maternal smoking| early-childhood| risk-factors| parental smoking| 1st year| atopic-dermatitis| socioeconomic-status	Burke, H; Leonardi-Bee, J; Hashim, A; Pine-Abata, H; Chen, YL; Cook, DG; Britton, JR; McKeever, TM	Prenatal and Passive Smoke Exposure and Incidence of Asthma and Wheeze: Systematic Review and Meta-analysis		PEDIATRICS	asthma; wheeze; passive smoking exposure; meta-analysis	PROSPECTIVE BIRTH COHORT; ENVIRONMENTAL TOBACCO-SMOKE; BODY-MASS INDEX; MATERNAL SMOKING; EARLY-CHILDHOOD; RISK-FACTORS; PARENTAL SMOKING; 1ST YEAR; ATOPIC-DERMATITIS; SOCIOECONOMIC-STATUS	OBJECTIVES: Exposure to passive smoke is a common and avoidable risk factor for wheeze and asthma in children. Substantial growth in the prospective cohort study evidence base provides an opportunity to generate new and more detailed estimates of the magnitude of the effect. A systematic review and meta-analysis was conducted to provide estimates of the prospective effect of smoking by parents or household members on the risk of wheeze and asthma at different stages of childhood. METHODS: We systematically searched Medline, Embase, and conference abstracts to identify cohort studies of the incidence of asthma or wheeze in relation to exposure to prenatal or postnatal maternal, paternal, or household smoking in subjects aged up to 18 years old. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by using random effects model. RESULTS: We identified 79 prospective studies. Exposure to pre-or postnatal passive smoke exposure was associated with a 30% to 70% increased risk of incident wheezing (strongest effect from postnatal maternal smoking on wheeze in children aged <= 2 years, OR = 1.70, 95% CI = 1.24-2.35, 4 studies) and a 21% to 85% increase in incident asthma (strongest effect from prenatal maternal smoking on asthma in children aged <= 2 years, OR = 1.85, 95% CI = 1.35-2.53, 5 studies). CONCLUSIONS: Building upon previous findings, exposure to passive smoking increases the incidence of wheeze and asthma in children and young people by at least 20%. Preventing parental smoking is crucially important to the prevention of asthma. Pediatrics 2012;129:735-744	88	190	2012	10	10.1542/peds.2011-2196	Pediatrics
Exhaled Nitric Oxide in Pulmonary Diseases A Comprehensive Review. The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be monitored easily in exhaled air. It is now possible to estimate the predominant site of increased fraction of exhaled NO (FENO) and its potential pathologic and physiologic role in various pulmonary diseases. In asthma, increased FENO reflects eosinophilic-mediated inflammatory pathways moderately well in central and/or peripheral airway sites and implies increased inhaled and systemic corticosteroid responsiveness. Recently, five randomized controlled algorithm asthma trials reported only equivocal benefits of adding measurements of FENO to usual clinical guideline management including spirometry; however, significant design issues may exist. Overall, FENO measurement at a single expiratory flow rate of 50 mL/s may be an important adjunct for diagnosis and management in selected cases of asthma. This may supplement standard clinical asthma care guidelines, including spirometry, providing a noninvasive window into predominantly large-airway-presumed eosinophilic inflammation. In COPD, large/central airway maximal NO flux and peripheral/small airway/alveolar NO concentration may be normal and the role of FENO monitoring is less clear and therefore less established than in asthma. Furthermore, concurrent smoking reduces FENO. Monitoring FENO in pulmonary hypertension and cystic fibrosis has opened up a window to the role NO may play in their pathogenesis and possible clinical benefits in the management of these diseases. CHEST 2010; 138(3):682-692. randomized controlled-trial| eosinophilic airway inflammation| dose-response relationship| cystic-fibrosis| axial diffusion| asthmatic-patients| healthy-volunteers| exchange dynamics| childhood asthma| reference values.	SEP-2010	randomized controlled-trial| eosinophilic airway inflammation| dose-response relationship| cystic-fibrosis| axial diffusion| asthmatic-patients| healthy-volunteers| exchange dynamics| childhood asthma| reference values	Barnes, PJ; Dweik, RA; Gelb, AF; Gibson, PG; George, SC; Grasemann, H; Pavord, ID; Ratjen, F; Silkoff, PE; Taylor, DR; Zamel, N	Exhaled Nitric Oxide in Pulmonary Diseases A Comprehensive Review		CHEST		RANDOMIZED CONTROLLED-TRIAL; EOSINOPHILIC AIRWAY INFLAMMATION; DOSE-RESPONSE RELATIONSHIP; CYSTIC-FIBROSIS; AXIAL DIFFUSION; ASTHMATIC-PATIENTS; HEALTHY-VOLUNTEERS; EXCHANGE DYNAMICS; CHILDHOOD ASTHMA; REFERENCE VALUES	The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be monitored easily in exhaled air. It is now possible to estimate the predominant site of increased fraction of exhaled NO (FENO) and its potential pathologic and physiologic role in various pulmonary diseases. In asthma, increased FENO reflects eosinophilic-mediated inflammatory pathways moderately well in central and/or peripheral airway sites and implies increased inhaled and systemic corticosteroid responsiveness. Recently, five randomized controlled algorithm asthma trials reported only equivocal benefits of adding measurements of FENO to usual clinical guideline management including spirometry; however, significant design issues may exist. Overall, FENO measurement at a single expiratory flow rate of 50 mL/s may be an important adjunct for diagnosis and management in selected cases of asthma. This may supplement standard clinical asthma care guidelines, including spirometry, providing a noninvasive window into predominantly large-airway-presumed eosinophilic inflammation. In COPD, large/central airway maximal NO flux and peripheral/small airway/alveolar NO concentration may be normal and the role of FENO monitoring is less clear and therefore less established than in asthma. Furthermore, concurrent smoking reduces FENO. Monitoring FENO in pulmonary hypertension and cystic fibrosis has opened up a window to the role NO may play in their pathogenesis and possible clinical benefits in the management of these diseases. CHEST 2010; 138(3):682-692	111	190	2010	11	10.1378/chest.09-2090	General & Internal Medicine; Respiratory System
Tregs and allergic disease. Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect up to 15% of populations in Westernized countries. The description of Tregs as T cells that prevent development of autoinumme disease led to considerable interest in whether these Tregs were also normally involved in prevention of sensitization to allergens and whether it might be possible to manipulate Tregs for the therapy of allergic disease. Current data suggest that Th2 responses to allergens are normally suppressed by both CD4(+)CD25(+) Tregs and IL-10 Tregs. Furthermore, suppression by these subsets is decreased in allergic individuals. In animal models, Tregs could be induced by high- or low-dose inhaled antigen, and prior induction of such Tregs prevented subsequent development of allergen sensitization and airway inflammation in inhaled challenge models. For many years, allergen-injection immunotherapy has been used for the therapy of allergic disease, and this treatment may induce IL-10 Tregs, leading to both suppression of Th2 responses and a switch from IgE to IgG4 antibody production. Improvements in allergen immunotherapy, such as peptide therapy, and greater understanding of the biology of Tregs hold great promise for the treatment and prevention of allergic disease.. regulatory t-cells| grass-pollen immunotherapy| immunological self-tolerance| late asthmatic reactions| cows milk allergy| experimental autoimmune encephalomyelitis| transcription factor foxp3| myelin basic-protein| house-dust mite| in-vitro.	NOV-2004	regulatory t-cells| grass-pollen immunotherapy| immunological self-tolerance| late asthmatic reactions| cows milk allergy| experimental autoimmune encephalomyelitis| transcription factor foxp3| myelin basic-protein| house-dust mite| in-vitro	Robinson, DS; Larche, M; Durham, SR	Tregs and allergic disease		JOURNAL OF CLINICAL INVESTIGATION		REGULATORY T-CELLS; GRASS-POLLEN IMMUNOTHERAPY; IMMUNOLOGICAL SELF-TOLERANCE; LATE ASTHMATIC REACTIONS; COWS MILK ALLERGY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TRANSCRIPTION FACTOR FOXP3; MYELIN BASIC-PROTEIN; HOUSE-DUST MITE; IN-VITRO	Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect up to 15% of populations in Westernized countries. The description of Tregs as T cells that prevent development of autoinumme disease led to considerable interest in whether these Tregs were also normally involved in prevention of sensitization to allergens and whether it might be possible to manipulate Tregs for the therapy of allergic disease. Current data suggest that Th2 responses to allergens are normally suppressed by both CD4(+)CD25(+) Tregs and IL-10 Tregs. Furthermore, suppression by these subsets is decreased in allergic individuals. In animal models, Tregs could be induced by high- or low-dose inhaled antigen, and prior induction of such Tregs prevented subsequent development of allergen sensitization and airway inflammation in inhaled challenge models. For many years, allergen-injection immunotherapy has been used for the therapy of allergic disease, and this treatment may induce IL-10 Tregs, leading to both suppression of Th2 responses and a switch from IgE to IgG4 antibody production. Improvements in allergen immunotherapy, such as peptide therapy, and greater understanding of the biology of Tregs hold great promise for the treatment and prevention of allergic disease.	110	190	2004	9	10.1172/JCI200423595	Research & Experimental Medicine
Assessment of quality of life in children with peanut allergy. Children with a peanut allergy (PA) are faced with food and social restrictions due to the potentially life-threatening nature of their disease, for which there is no cure or treatment. This inevitably impacts upon their quality of life (QoL). QoL of 20 children with PA and 20 children with insulin-dependent diabetes mellitus (IDDM) was measured using two disease-specific QoL questionnaires (higher scores correspond to a poorer QoL). One questionnaire was designed by us and the other was adapted from the Vespid Allergy QoL questionnaire. We gave subjects cameras to record how their QoL is affected over a 24-h period. Response rates for both questionnaires were 100%. Mean ages were 9.0 and 10.4 years for PA and IDDM subjects, respectively. Children with a PA reported a poorer quality of life than children with IDDM: mean scores were 54.85 for PA subjects and 46.40 for diabetics (p = 0.004) in questionnaire 1 and 54.30 and 34.50 (pless than or equal to0.001) in questionnaire 2. PA children reported more fear of an adverse event and more anxiety about eating, especially when eating away from home. Photographs fell into seven common categories: food, management, environment, away from home, physical activities, restaurant and people. Most photographs related to food and management issues and revealed difficulties for both groups regarding food restrictions. PA subjects felt more threatened by potential hazards within their environment, felt more restricted by their PA regarding physical activities, and worried more about being away from home. However, they felt safe when carrying epinephrine kits and were positive about eating at familiar restaurants. The QoL in children with PA is more impaired than in children with IDDM. Their anxiety may be considered useful in some situations, promoting better adherence to allergen avoidance advice and rescue plans.. quality of life| peanut allergy| children.	OCT-2003	quality of life| peanut allergy| children	Avery, NJ; King, RM; Knight, S; Hourihane, JO	Assessment of quality of life in children with peanut allergy		PEDIATRIC ALLERGY AND IMMUNOLOGY	quality of life; peanut allergy; children		Children with a peanut allergy (PA) are faced with food and social restrictions due to the potentially life-threatening nature of their disease, for which there is no cure or treatment. This inevitably impacts upon their quality of life (QoL). QoL of 20 children with PA and 20 children with insulin-dependent diabetes mellitus (IDDM) was measured using two disease-specific QoL questionnaires (higher scores correspond to a poorer QoL). One questionnaire was designed by us and the other was adapted from the Vespid Allergy QoL questionnaire. We gave subjects cameras to record how their QoL is affected over a 24-h period. Response rates for both questionnaires were 100%. Mean ages were 9.0 and 10.4 years for PA and IDDM subjects, respectively. Children with a PA reported a poorer quality of life than children with IDDM: mean scores were 54.85 for PA subjects and 46.40 for diabetics (p = 0.004) in questionnaire 1 and 54.30 and 34.50 (pless than or equal to0.001) in questionnaire 2. PA children reported more fear of an adverse event and more anxiety about eating, especially when eating away from home. Photographs fell into seven common categories: food, management, environment, away from home, physical activities, restaurant and people. Most photographs related to food and management issues and revealed difficulties for both groups regarding food restrictions. PA subjects felt more threatened by potential hazards within their environment, felt more restricted by their PA regarding physical activities, and worried more about being away from home. However, they felt safe when carrying epinephrine kits and were positive about eating at familiar restaurants. The QoL in children with PA is more impaired than in children with IDDM. Their anxiety may be considered useful in some situations, promoting better adherence to allergen avoidance advice and rescue plans.	12	190	2003	5	10.1034/j.1399-3038.2003.00072.x	Allergy; Immunology; Pediatrics
Antenatal determinants of neonatal immune responses to allergens. Background The environmental factors responsible for recent increases in the prevalence of asthma and atopic disease have been assumed to act after birth. Their possible effects on fetal immune development in utero have not been investigated systematically, although sensitization to allergens may occur before birth. Objective This prospective study determined whether the risk factors for asthma and atopic disease, namely family history of atopic disease, maternal smoking, birth order, or maternal dietary intake of antioxidant vitamins, exert antenatal effects on the fetal immune system that may predispose to childhood atopy. Methods The T helper (Th) cell proliferative responses of cord blood mononuclear cells (CBMC) from a sample of 223 neonates, representative of children born to a cohort of 2000 pregnant women, were measured and related to family, maternal and environmental factors associated with the pregnancy. Results The magnitude of CBMC-proliferative responses to allergens increased significantly in association with a family history of atopic disease or maternal smoking, and decreased significantly with increasing birth order and high maternal dietary intake of vitamin E. The epidemiological association between birth order and atopy may therefore be a consequence of antenatal influences rather than of protective effects of childhood infections. The association between maternal intake of vitamin E and CBMC responsiveness suggests that diet during pregnancy may influence the fetal immune system in such a way as to modulate the risk of childhood atopy. Conclusion These results provide a new insight into the aetiology of atopic disease by demonstrating that the maternal environmental risk factors for atopy, diet, birth order and smoking, influence the development of the fetal immune system. This raises the prospect of preventative public health interventions during pregnancy.. atopy| t helper cells| antenatal influences| smoking| birth order| vitamin e|cell proliferative responses| umbilical-cord blood| house-dust-mite| respiratory symptoms| aberdeen schoolchildren| asthma| atopy| gamma| life| responsiveness.	JAN-2002	atopy| t helper cells| antenatal influences| smoking| birth order| vitamin e|cell proliferative responses| umbilical-cord blood| house-dust-mite| respiratory symptoms| aberdeen schoolchildren| asthma| atopy| gamma| life| responsiveness	Devereux, G; Barker, RN; Seaton, A	Antenatal determinants of neonatal immune responses to allergens		CLINICAL AND EXPERIMENTAL ALLERGY	atopy; T helper cells; antenatal influences; smoking; birth order; vitamin E	CELL PROLIFERATIVE RESPONSES; UMBILICAL-CORD BLOOD; HOUSE-DUST-MITE; RESPIRATORY SYMPTOMS; ABERDEEN SCHOOLCHILDREN; ASTHMA; ATOPY; GAMMA; LIFE; RESPONSIVENESS	Background The environmental factors responsible for recent increases in the prevalence of asthma and atopic disease have been assumed to act after birth. Their possible effects on fetal immune development in utero have not been investigated systematically, although sensitization to allergens may occur before birth. Objective This prospective study determined whether the risk factors for asthma and atopic disease, namely family history of atopic disease, maternal smoking, birth order, or maternal dietary intake of antioxidant vitamins, exert antenatal effects on the fetal immune system that may predispose to childhood atopy. Methods The T helper (Th) cell proliferative responses of cord blood mononuclear cells (CBMC) from a sample of 223 neonates, representative of children born to a cohort of 2000 pregnant women, were measured and related to family, maternal and environmental factors associated with the pregnancy. Results The magnitude of CBMC-proliferative responses to allergens increased significantly in association with a family history of atopic disease or maternal smoking, and decreased significantly with increasing birth order and high maternal dietary intake of vitamin E. The epidemiological association between birth order and atopy may therefore be a consequence of antenatal influences rather than of protective effects of childhood infections. The association between maternal intake of vitamin E and CBMC responsiveness suggests that diet during pregnancy may influence the fetal immune system in such a way as to modulate the risk of childhood atopy. Conclusion These results provide a new insight into the aetiology of atopic disease by demonstrating that the maternal environmental risk factors for atopy, diet, birth order and smoking, influence the development of the fetal immune system. This raises the prospect of preventative public health interventions during pregnancy.	35	190	2002	8	10.1046/j.0022-0477.2001.01267.x	Allergy; Immunology
The pathophysiology of asthma. Asthma is a chronic disorder of the airways that is characterized by reversible airflow obstruction and airway inflammation, persistent airway hyper-reactivity, and airway remodeling. The etiology of asthma is complex and multifactorial. Recent advances have demonstrated the importance of genetics in the development of asthma, particularly atopic asthma. Environmental stimuli, particularly early childhood infections, have also been associated with the development of asthma. Most current data seem to suggest that these factors drive the development of a Th-2 lymphocyte-predominant immune response, which has been associated with atopy and IgE-mediated inflammation. The concept of reversible airflow obstruction has also recently been challenged. It is now clear that chronic airway changes occur, which may contribute to progressive airflow obstruction. We discuss the important influence of genetic and environmental factors on the emergence of the asthmatic phenotype. The significance of Th-1 and Th-2 lymphocyte-mediated immunity are discussed, and the inflammatory processes leading to chronic airway inflammation are detailed.. atopy| cytokines| th-2 cells| airway obstruction| bronchial hyperreactivity| lungs|genome-wide search| endotoxin exposure-response| allergen-specific th1| ri-beta gene| bronchial hyperresponsiveness| beta(2)-adrenergic receptor| innate immunity| segregation analysis| atopic asthma| cotton dust.	2002	atopy| cytokines| th-2 cells| airway obstruction| bronchial hyperreactivity| lungs|genome-wide search| endotoxin exposure-response| allergen-specific th1| ri-beta gene| bronchial hyperresponsiveness| beta(2)-adrenergic receptor| innate immunity| segregation analysis| atopic asthma| cotton dust	Maddox, L; Schwartz, DA	The pathophysiology of asthma		ANNUAL REVIEW OF MEDICINE	atopy; cytokines; Th-2 cells; airway obstruction; bronchial hyperreactivity; lungs	GENOME-WIDE SEARCH; ENDOTOXIN EXPOSURE-RESPONSE; ALLERGEN-SPECIFIC TH1; RI-BETA GENE; BRONCHIAL HYPERRESPONSIVENESS; BETA(2)-ADRENERGIC RECEPTOR; INNATE IMMUNITY; SEGREGATION ANALYSIS; ATOPIC ASTHMA; COTTON DUST	Asthma is a chronic disorder of the airways that is characterized by reversible airflow obstruction and airway inflammation, persistent airway hyper-reactivity, and airway remodeling. The etiology of asthma is complex and multifactorial. Recent advances have demonstrated the importance of genetics in the development of asthma, particularly atopic asthma. Environmental stimuli, particularly early childhood infections, have also been associated with the development of asthma. Most current data seem to suggest that these factors drive the development of a Th-2 lymphocyte-predominant immune response, which has been associated with atopy and IgE-mediated inflammation. The concept of reversible airflow obstruction has also recently been challenged. It is now clear that chronic airway changes occur, which may contribute to progressive airflow obstruction. We discuss the important influence of genetic and environmental factors on the emergence of the asthmatic phenotype. The significance of Th-1 and Th-2 lymphocyte-mediated immunity are discussed, and the inflammatory processes leading to chronic airway inflammation are detailed.	150	190	2002	22	10.1146/annurev.med.53.082901.103921	General & Internal Medicine
Mechanisms of chromium toxicity, carcinogenicity and allergenicity: Review of the literature from 1985 to 2000. Laboratory and clinical reports about the pathogenesis of the carcinogenicity and allergenicity of chromium compounds published between 1985 and 2000 have been reviewed as a basis for consideration of the pathogenetic mechanisms involved. There is good evidence from the clinic and the laboratory that Cr[VI] is the ion responsible for most of the toxic actions, although much of the underlying molecular damage may be due to its intracellular reduction to the even more highly reactive and short-lived chemical species Cr[III] and Cr[V]. Exposure to Cr[VI] can result in various point mutations in DNA and to chromosomal damage, as well as to oxidative changes in proteins and to adduct formation. The relative importance of these effects of chromium ions and of the free oxidising radicals they may generate in the body in causing tumours and allergic sensitisation remain to be demonstrated. Biochemical studies of the DNA-damaging effects and of the pathogenesis of the allergic reactions to chromium ions have not kept up with advances in understanding of the molecular basis of the effects of other carcinogens and allergens.. chromium| toxicity| allergenicity| carcinogenicity| genotoxicity| biochemical mechanisms|single-strand breaks| hexavalent chromium| alveolar macrophages| ascorbic-acid| cross-links| dna-damage| in-vitro| reduction| glutathione| exposure.	SEP-2001	chromium| toxicity| allergenicity| carcinogenicity| genotoxicity| biochemical mechanisms|single-strand breaks| hexavalent chromium| alveolar macrophages| ascorbic-acid| cross-links| dna-damage| in-vitro| reduction| glutathione| exposure	Dayan, AD; Paine, AJ	Mechanisms of chromium toxicity, carcinogenicity and allergenicity: Review of the literature from 1985 to 2000		HUMAN & EXPERIMENTAL TOXICOLOGY	chromium; toxicity; allergenicity; carcinogenicity; genotoxicity; biochemical mechanisms	SINGLE-STRAND BREAKS; HEXAVALENT CHROMIUM; ALVEOLAR MACROPHAGES; ASCORBIC-ACID; CROSS-LINKS; DNA-DAMAGE; IN-VITRO; REDUCTION; GLUTATHIONE; EXPOSURE	Laboratory and clinical reports about the pathogenesis of the carcinogenicity and allergenicity of chromium compounds published between 1985 and 2000 have been reviewed as a basis for consideration of the pathogenetic mechanisms involved. There is good evidence from the clinic and the laboratory that Cr[VI] is the ion responsible for most of the toxic actions, although much of the underlying molecular damage may be due to its intracellular reduction to the even more highly reactive and short-lived chemical species Cr[III] and Cr[V]. Exposure to Cr[VI] can result in various point mutations in DNA and to chromosomal damage, as well as to oxidative changes in proteins and to adduct formation. The relative importance of these effects of chromium ions and of the free oxidising radicals they may generate in the body in causing tumours and allergic sensitisation remain to be demonstrated. Biochemical studies of the DNA-damaging effects and of the pathogenesis of the allergic reactions to chromium ions have not kept up with advances in understanding of the molecular basis of the effects of other carcinogens and allergens.	72	190	2001	13	10.1191/096032701682693062	Toxicology
SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. The effects of a second generation p38 mitogen-activated protein kinase (MAPK) inhibitor, SB 239063 [trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyridimidin-4-yl) imidazole; IC50 = 44 nM vs. p38 alpha], were assessed in models that represent different pathological aspects of chronic obstructive pulmonary disease (COPD) [airway neutrophilia, enhanced cytokine formation and increased matrix metalloproteinase (MMP)-9 activity] and in a model of lung fibrosis. Airway neutrophil infiltration and interleukin (IL)-6 levels, assessed by bronchoalveolar lavage 48 h after lipopolysaccharide (LPS) inhalation, were inhibited dose dependently by 3-30 mg/kg of SB 239063 given orally twice a day. In addition, SB 239063 (30 mg/kg orally) attenuated IL-6 bronchoalveolar lavage fluid concentrations (>90% inhibition) and MMP-9 activity (64% inhibition) assessed 6 h after LPS exposure. In guinea pig cultured alveolar macrophages, SB 239063 inhibited LPS-induced IL-6 production (IC50 of 362 nM). In a bleomycin-induced pulmonary fibrosis model in rats, treatment with SB 239063 (2.4 or 4.8 mg/day via osmotic pump) significantly inhibited bleomycin-induced right ventricular hypertrophy (indicative of secondary pulmonary hypertension) and increases in lung hydroxyproline synthesis (indicative of collagen synthesis and fibrosis). Therefore, SB 239063 demonstrates activity against a range of sequelae commonly associated with COPD and fibrosis, supporting the therapeutic potential of p38 MAPK inhibitors such as SB 239063 in chronic airway disease.. chronic obstructive pulmonary disease| interleukin-6| bleomycin| alveolar macrophage| mitogen-activated protein kinase| matrix metalloproteinase-9|obstructive pulmonary-disease| activated protein-kinase| cor-pulmonale| asthma| pathophysiology| interleukin-6| expression| macrophage| release| stress.	NOV-2000	chronic obstructive pulmonary disease| interleukin-6| bleomycin| alveolar macrophage| mitogen-activated protein kinase| matrix metalloproteinase-9|obstructive pulmonary-disease| activated protein-kinase| cor-pulmonale| asthma| pathophysiology| interleukin-6| expression| macrophage| release| stress	Underwood, DC; Osborn, RR; Bochnowicz, S; Webb, EF; Rieman, DJ; Lee, JC; Romanic, AM; Adams, JL; Hay, DWP; Griswold, DE	SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung		AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY	chronic obstructive pulmonary disease; interleukin-6; bleomycin; alveolar macrophage; mitogen-activated protein kinase; matrix metalloproteinase-9	OBSTRUCTIVE PULMONARY-DISEASE; ACTIVATED PROTEIN-KINASE; COR-PULMONALE; ASTHMA; PATHOPHYSIOLOGY; INTERLEUKIN-6; EXPRESSION; MACROPHAGE; RELEASE; STRESS	The effects of a second generation p38 mitogen-activated protein kinase (MAPK) inhibitor, SB 239063 [trans-1-(4-hydroxycyclohexyl)-4-(4-fluorophenyl)-5-(2-methoxypyridimidin-4-yl) imidazole; IC50 = 44 nM vs. p38 alpha], were assessed in models that represent different pathological aspects of chronic obstructive pulmonary disease (COPD) [airway neutrophilia, enhanced cytokine formation and increased matrix metalloproteinase (MMP)-9 activity] and in a model of lung fibrosis. Airway neutrophil infiltration and interleukin (IL)-6 levels, assessed by bronchoalveolar lavage 48 h after lipopolysaccharide (LPS) inhalation, were inhibited dose dependently by 3-30 mg/kg of SB 239063 given orally twice a day. In addition, SB 239063 (30 mg/kg orally) attenuated IL-6 bronchoalveolar lavage fluid concentrations (>90% inhibition) and MMP-9 activity (64% inhibition) assessed 6 h after LPS exposure. In guinea pig cultured alveolar macrophages, SB 239063 inhibited LPS-induced IL-6 production (IC50 of 362 nM). In a bleomycin-induced pulmonary fibrosis model in rats, treatment with SB 239063 (2.4 or 4.8 mg/day via osmotic pump) significantly inhibited bleomycin-induced right ventricular hypertrophy (indicative of secondary pulmonary hypertension) and increases in lung hydroxyproline synthesis (indicative of collagen synthesis and fibrosis). Therefore, SB 239063 demonstrates activity against a range of sequelae commonly associated with COPD and fibrosis, supporting the therapeutic potential of p38 MAPK inhibitors such as SB 239063 in chronic airway disease.	32	190	2000	8		Physiology; Respiratory System
The respiratory health hazards of volcanic ash: a review for volcanic risk mitigation. Studies of the respiratory health effects of different types of volcanic ash have been undertaken only in the last 40 years, and mostly since the eruption of Mt. St. Helens in 1980. This review of all published clinical, epidemiological and toxicological studies, and other work known to the authors up to and including 2005, highlights the sparseness of studies on acute health effects after eruptions and the complexity of evaluating the long-term health risk (silicosis, non-specific pneumoconiosis and chronic obstructive pulmonary disease) in populations from prolonged exposure to ash due to persistent eruptive activity. The acute and chronic health effects of volcanic ash depend upon particle size (particularly the proportion of respirable-sized material), mineralogical composition (including the crystalline silica content) and the physicochemical properties of the surfaces of the ash particles, all of which vary between volcanoes and even eruptions of the same volcano, but adequate information on these key characteristics is not reported for most eruptions. The incidence of acute respiratory symptoms (e.g. asthma, bronchitis) varies greatly after ashfalls, from very few, if any, reported cases to population outbreaks of asthma. The studies are inadequate for excluding increases in acute respiratory mortality after eruptions. Individuals with preexisting lung disease, including asthma, can be at increased risk of their symptoms being exacerbated after falls of fine ash. A comprehensive risk assessment, including toxicological studies, to determine the long-term risk of silicosis from chronic exposure to volcanic ash, has been under-taken only in the eruptions of Mt. St. Helens (1980), USA, and Soufriere Hills, Montserrat (1995 onwards). In the Soufriere Hills eruption, a long-term silicosis hazard has been identified and sufficient exposure and toxicological information obtained to make a probabilistic risk assessment for the development of silicosis in outdoor workers and the general population. A more systematic approach to multi-disciplinary studies in future eruptions is recommended, including establishing an archive of ash samples and a website containing health advice for the public, together with scientific and medical study guidelines for volcanologists and health-care workers.. volcanic ash| respiratory| health| hazard| risk mitigation| review|mount-st-helens| soufriere hills volcano| british-west-indies| particulate air-pollution| pulmonary toxicity| new-zealand| crystalline silica| lung-function| montserrat| eruption.	JUL-2006	volcanic ash| respiratory| health| hazard| risk mitigation| review|mount-st-helens| soufriere hills volcano| british-west-indies| particulate air-pollution| pulmonary toxicity| new-zealand| crystalline silica| lung-function| montserrat| eruption	Horwell, CJ; Baxter, PJ	The respiratory health hazards of volcanic ash: a review for volcanic risk mitigation		BULLETIN OF VOLCANOLOGY	volcanic ash; respiratory; health; hazard; risk mitigation; review	MOUNT-ST-HELENS; SOUFRIERE HILLS VOLCANO; BRITISH-WEST-INDIES; PARTICULATE AIR-POLLUTION; PULMONARY TOXICITY; NEW-ZEALAND; CRYSTALLINE SILICA; LUNG-FUNCTION; MONTSERRAT; ERUPTION	Studies of the respiratory health effects of different types of volcanic ash have been undertaken only in the last 40 years, and mostly since the eruption of Mt. St. Helens in 1980. This review of all published clinical, epidemiological and toxicological studies, and other work known to the authors up to and including 2005, highlights the sparseness of studies on acute health effects after eruptions and the complexity of evaluating the long-term health risk (silicosis, non-specific pneumoconiosis and chronic obstructive pulmonary disease) in populations from prolonged exposure to ash due to persistent eruptive activity. The acute and chronic health effects of volcanic ash depend upon particle size (particularly the proportion of respirable-sized material), mineralogical composition (including the crystalline silica content) and the physicochemical properties of the surfaces of the ash particles, all of which vary between volcanoes and even eruptions of the same volcano, but adequate information on these key characteristics is not reported for most eruptions. The incidence of acute respiratory symptoms (e.g. asthma, bronchitis) varies greatly after ashfalls, from very few, if any, reported cases to population outbreaks of asthma. The studies are inadequate for excluding increases in acute respiratory mortality after eruptions. Individuals with preexisting lung disease, including asthma, can be at increased risk of their symptoms being exacerbated after falls of fine ash. A comprehensive risk assessment, including toxicological studies, to determine the long-term risk of silicosis from chronic exposure to volcanic ash, has been under-taken only in the eruptions of Mt. St. Helens (1980), USA, and Soufriere Hills, Montserrat (1995 onwards). In the Soufriere Hills eruption, a long-term silicosis hazard has been identified and sufficient exposure and toxicological information obtained to make a probabilistic risk assessment for the development of silicosis in outdoor workers and the general population. A more systematic approach to multi-disciplinary studies in future eruptions is recommended, including establishing an archive of ash samples and a website containing health advice for the public, together with scientific and medical study guidelines for volcanologists and health-care workers.	140	189	2006	24	10.1007/s00445-006-0052-y	Geology
Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial. Background Asthma places huge demands on healthcare services, and its prevalence is increasing. Reduction of exposure to environmental allergens could offer a realistic chance for primary prevention. Our aim was to ascertain whether or not living in a low-allergen environment reduces the risk of asthma and atopic diseases in infants. Methods We assigned infants to four risk groups according to parental atopic status. We enrolled 291 high-risk couples (both parents atopic, no pets) into a prospective, prenatally randomised, cohort study, and allocated them to environmental manipulation, in which measures to reduce prenatal and postnatal allergen exposure were undertaken (active HRA) (n=145) or no intervention (control HRC) (n=146). Two further prospective groups were studied: 161 high-risk infants with pets in the home (HRP group) and 168 low-risk infants, whose parents were both non-atopic (LR group). The main outcome measures were signs and symptoms of atopic disease at 1 year of age. Findings 103 families dropped out or were lost to follow up. At age 1 year we followed-up 133 HRA, 118 HRC, 140 HRP, and 126 LR infants. Children in the HRA group were less likely to have respiratory symptoms during the first year of life than those in the HRC group. The most pronounced differences were in the relative risks for severe wheeze with shortness of breath (relative risk 0.44 [95% CI 0.20-1.00]), prescribed medication for the treatment of wheezy attacks (0.58 [0.36-0.95]), and wheezing after vigorous playing, crying, or exertion (0.18 [0.04-0.79]). Probability of respiratory symptoms in HRC and HRP infants was similar, whereas it was much lower in the LR than in the HRC group. Cat ownership was significantly associated with sensitisation to cats (24.6 [3.04-199.05]; p=0.003). Interpretation Environmental manipulation reduces some respiratory symptoms in the first year of life in high-risk infants. Further follow up is needed, however, to ascertain whether living in a low-allergen environment reduces allergy and asthma in later life.. allergen avoidance| confidence-intervals| early exposure| risk factor| asthma| sensitization| children| infancy| cat| mite.	JUL 21-2001	allergen avoidance| confidence-intervals| early exposure| risk factor| asthma| sensitization| children| infancy| cat| mite	Custovic, A; Simpson, BM; Simpson, A; Kissen, P; Woodcock, A	Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial		LANCET		ALLERGEN AVOIDANCE; CONFIDENCE-INTERVALS; EARLY EXPOSURE; RISK FACTOR; ASTHMA; SENSITIZATION; CHILDREN; INFANCY; CAT; MITE	Background Asthma places huge demands on healthcare services, and its prevalence is increasing. Reduction of exposure to environmental allergens could offer a realistic chance for primary prevention. Our aim was to ascertain whether or not living in a low-allergen environment reduces the risk of asthma and atopic diseases in infants. Methods We assigned infants to four risk groups according to parental atopic status. We enrolled 291 high-risk couples (both parents atopic, no pets) into a prospective, prenatally randomised, cohort study, and allocated them to environmental manipulation, in which measures to reduce prenatal and postnatal allergen exposure were undertaken (active HRA) (n=145) or no intervention (control HRC) (n=146). Two further prospective groups were studied: 161 high-risk infants with pets in the home (HRP group) and 168 low-risk infants, whose parents were both non-atopic (LR group). The main outcome measures were signs and symptoms of atopic disease at 1 year of age. Findings 103 families dropped out or were lost to follow up. At age 1 year we followed-up 133 HRA, 118 HRC, 140 HRP, and 126 LR infants. Children in the HRA group were less likely to have respiratory symptoms during the first year of life than those in the HRC group. The most pronounced differences were in the relative risks for severe wheeze with shortness of breath (relative risk 0.44 [95% CI 0.20-1.00]), prescribed medication for the treatment of wheezy attacks (0.58 [0.36-0.95]), and wheezing after vigorous playing, crying, or exertion (0.18 [0.04-0.79]). Probability of respiratory symptoms in HRC and HRP infants was similar, whereas it was much lower in the LR than in the HRC group. Cat ownership was significantly associated with sensitisation to cats (24.6 [3.04-199.05]; p=0.003). Interpretation Environmental manipulation reduces some respiratory symptoms in the first year of life in high-risk infants. Further follow up is needed, however, to ascertain whether living in a low-allergen environment reduces allergy and asthma in later life.	24	189	2001	6	10.1016/S0140-6736(01)05406-X	General & Internal Medicine
Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression. Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 (Th2)-mediated allergic airway inflammation in mice. However, it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness. Here, we analyzed the effects of locally antagonizing GATA-3 function in a murine model of asthma. We could suppress GATA-3 expression in interleukin (IL)-4-producing T cells in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the translation start site of GATA-3, whereas nonsense control oligonucleotides were virtually inactive. In a murine model of asthma associated with allergic pulmonary inflammation and hyperresponsiveness in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate-labeled GATA-3 antisense oligonucleotides led to DNA uptake in lung cells associated with a reduction of intracellular GATA-3 expression. Such intrapulmonary blockade of GATA-3 expression caused an abrogation of signs of lung inflammation including infiltration of eosinophils and Th2 cytokine production. Furthermore, treatment with antisense but not nonsense oligonucleotides induced a significant reduction of airway hyperresponsiveness in OVA-sensitized mice to levels comparable to saline-treated control mice, as assessed by both enhanced pause (PenH) responses and pulmonary resistance determined by body plethysmography. These data indicate a critical role for GATA-3 in the effector phase of a murine asthma model and suggest that local delivery of GATA-3 antisense oligonucleotides may be a novel approach for the treatment of air-way hyperresponsiveness such as in asthma. This approach has the potential advantage of suppressing the expression of various proinflammatory Th2 cytokines simultaneously rather than suppressing the activity of a single cytokine.. gata-3 antisense dna| asthma| t cells| th2 cytokines|transcription factor gata-3| chronic intestinal inflammation| developing th1 cells| cd4(+) t-cells| mouse model| th2-specific expression| gene-expression| transgenic mice| atopic asthma| murine model.	JUN 4-2001	gata-3 antisense dna| asthma| t cells| th2 cytokines|transcription factor gata-3| chronic intestinal inflammation| developing th1 cells| cd4(+) t-cells| mouse model| th2-specific expression| gene-expression| transgenic mice| atopic asthma| murine model	Finotto, S; De Sanctis, GT; Lehr, HA; Herz, U; Buerke, M; Schipp, M; Bartsch, B; Atreya, R; Schmitt, E; Galle, PR; Renz, H; Neurath, MF	Treatment of allergic airway inflammation and hyperresponsiveness by antisense-induced local blockade of GATA-3 expression		JOURNAL OF EXPERIMENTAL MEDICINE	GATA-3 antisense DNA; asthma; T cells; Th2 cytokines	TRANSCRIPTION FACTOR GATA-3; CHRONIC INTESTINAL INFLAMMATION; DEVELOPING TH1 CELLS; CD4(+) T-CELLS; MOUSE MODEL; TH2-SPECIFIC EXPRESSION; GENE-EXPRESSION; TRANSGENIC MICE; ATOPIC ASTHMA; MURINE MODEL	Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 (Th2)-mediated allergic airway inflammation in mice. However, it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness. Here, we analyzed the effects of locally antagonizing GATA-3 function in a murine model of asthma. We could suppress GATA-3 expression in interleukin (IL)-4-producing T cells in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the translation start site of GATA-3, whereas nonsense control oligonucleotides were virtually inactive. In a murine model of asthma associated with allergic pulmonary inflammation and hyperresponsiveness in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate-labeled GATA-3 antisense oligonucleotides led to DNA uptake in lung cells associated with a reduction of intracellular GATA-3 expression. Such intrapulmonary blockade of GATA-3 expression caused an abrogation of signs of lung inflammation including infiltration of eosinophils and Th2 cytokine production. Furthermore, treatment with antisense but not nonsense oligonucleotides induced a significant reduction of airway hyperresponsiveness in OVA-sensitized mice to levels comparable to saline-treated control mice, as assessed by both enhanced pause (PenH) responses and pulmonary resistance determined by body plethysmography. These data indicate a critical role for GATA-3 in the effector phase of a murine asthma model and suggest that local delivery of GATA-3 antisense oligonucleotides may be a novel approach for the treatment of air-way hyperresponsiveness such as in asthma. This approach has the potential advantage of suppressing the expression of various proinflammatory Th2 cytokines simultaneously rather than suppressing the activity of a single cytokine.	50	189	2001	14	10.1084/jem.193.11.1247	Immunology; Research & Experimental Medicine
Allergic Sensitization through the Airway Primes Th17-dependent Neutrophilia and Airway Hyperresponsiveness. Rationale: In humans, immune responses to inhaled aeroallergens develop in the lung and draining lymph nodes. Many animal models of asthma bypass this route and instead use intraperitoneal injections of allergen using aluminum hydroxide as an adjuvant. Objectives: We investigated whether allergic sensitization through the airway elicits immune responses qualitatively different than those arising in the peritoneum. Methods: Mice were sensitized to allergen through the airway using low-dose LIPS as an adjuvant, or through the peritoneum using aluminum hydroxide as an adjuvant. After a single allergen challenge, ELISA and flow cytometry were used to measure cytokines and leukocyte subsets. Invasive measurements of airway resistance were used to measure allergen-induced airway hyperreactivity (AHR). Measurements and Main Results: Sensitization through the peritoneum primed strong Th2 responses and eosinophilia, but not AHR, after a single allergen challenge. By contrast, allergic sensitization through the airway primed only modest Th2 responses, but strong Th17 responses. Th17 cells homed to the lung and released IL-17 into the airway on subsequent encounter with inhaled allergen. As a result, these mice developed IL-17-dependent airway neutrophilia and AHR. This AHR was neutrophil-dependent because it was abrogated in CXCR2-deficient mice and also in wild-type mice receiving a neutrophil-depleting antibody. Individually, neither IL-17 nor ongoing Th2 responses were sufficient to confer AHR, but together they acted synergistically to promote neutrophil recruitment, eosinophil recruitment and AHR. Conclusions: Allergic sensitization through the airway primes modest Th2 responses but strong Th17 responses that promote airway neutrophilia and acute AHR. These findings support a causal role for neutrophils in severe asthma.. asthma| lung| immunity|t-cells| eosinophilic inflammation| lung inflammation| th2 responses| severe asthma| antigen| interleukin-17| dissociation| chemokine| mice.	OCT 15-2009	asthma| lung| immunity|t-cells| eosinophilic inflammation| lung inflammation| th2 responses| severe asthma| antigen| interleukin-17| dissociation| chemokine| mice	Wilson, RH; Whitehead, GS; Nakano, H; Free, ME; Kolls, JK; Cook, DN	Allergic Sensitization through the Airway Primes Th17-dependent Neutrophilia and Airway Hyperresponsiveness		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; lung; immunity	T-CELLS; EOSINOPHILIC INFLAMMATION; LUNG INFLAMMATION; TH2 RESPONSES; SEVERE ASTHMA; ANTIGEN; INTERLEUKIN-17; DISSOCIATION; CHEMOKINE; MICE	Rationale: In humans, immune responses to inhaled aeroallergens develop in the lung and draining lymph nodes. Many animal models of asthma bypass this route and instead use intraperitoneal injections of allergen using aluminum hydroxide as an adjuvant. Objectives: We investigated whether allergic sensitization through the airway elicits immune responses qualitatively different than those arising in the peritoneum. Methods: Mice were sensitized to allergen through the airway using low-dose LIPS as an adjuvant, or through the peritoneum using aluminum hydroxide as an adjuvant. After a single allergen challenge, ELISA and flow cytometry were used to measure cytokines and leukocyte subsets. Invasive measurements of airway resistance were used to measure allergen-induced airway hyperreactivity (AHR). Measurements and Main Results: Sensitization through the peritoneum primed strong Th2 responses and eosinophilia, but not AHR, after a single allergen challenge. By contrast, allergic sensitization through the airway primed only modest Th2 responses, but strong Th17 responses. Th17 cells homed to the lung and released IL-17 into the airway on subsequent encounter with inhaled allergen. As a result, these mice developed IL-17-dependent airway neutrophilia and AHR. This AHR was neutrophil-dependent because it was abrogated in CXCR2-deficient mice and also in wild-type mice receiving a neutrophil-depleting antibody. Individually, neither IL-17 nor ongoing Th2 responses were sufficient to confer AHR, but together they acted synergistically to promote neutrophil recruitment, eosinophil recruitment and AHR. Conclusions: Allergic sensitization through the airway primes modest Th2 responses but strong Th17 responses that promote airway neutrophilia and acute AHR. These findings support a causal role for neutrophils in severe asthma.	35	188	2009	11	10.1164/rccm.200904-0573OC	General & Internal Medicine; Respiratory System
Racial and ethnic disparities in medical and dental health, access to care, and use of services in US children. BACKGROUND. Not enough is known about the national prevalence of racial/ethnic disparities in children's medical and dental care. OBJECTIVE. The purpose of this work was to examine racial/ethnic disparities in medical and oral health, access to care, and use of services in a national sample. METHODS. The National Survey of Children's Health was a telephone survey in 2003 2004 of a national random sample of parents and guardians of 102 353 children 0 to 17 years old. Disparities in selected medical and oral health and health care measures were examined for white, African American, Latino, Asian/Pacific Islander, Native American, and multiracial children. Multivariate analyses were performed to adjust for primary language at home, age, insurance coverage, income, parental education and employment, and number of children and adults in the household. Forty measures of medical and oral health status, access to care, and use of services were analyzed. RESULTS. Many significant disparities were noted; for example, uninsurance rates were 6% for whites, 21% for Latinos, 15% for Native Americans, 7% for African Americans, and 4% for Asians or Pacific Islanders, and the proportions with a usual source of care were as follows: whites, 90%; Native Americans, 61%; Latinos, 68%; African Americans, 77%; and Asians or Pacific Islanders, 87%. Many disparities persisted for >= 1 minority group in multivariate analyses, including increased odds of suboptimal health status, overweight, asthma, activity limitations, behavioral and speech problems, emotional difficulties, uninsurance, suboptimal dental health, no usual source of care, unmet medical and dental needs, transportation barriers to care, problems getting specialty care, no medical or dental visit in the past year, emergency department visits, not receiving mental health care, and not receiving prescription medications. Certain disparities were particularly marked for specific racial/ethnic groups: for Latinos, suboptimal health status and teeth condition, uninsurance, and problems getting specialty care; for African Americans, asthma, behavior problems, skin allergies, speech problems, and unmet prescription needs; for Native Americans, hearing or vision problems, no usual source of care, emergency department visits, and unmet medical and dental needs; and for Asians or Pacific Islanders, problems getting specialty care and not seeing a doctor in the past year. Multiracial children also experienced many disparities. CONCLUSIONS. Minority children experience multiple disparities in medical and oral health, access to care, and use of services. Certain disparities are particularly marked for specific racial/ethnic groups, and multiracial children experience many disparities.. disparities| minorities| children| race| ethnicity| african americans| hispanics| asians/pacific islanders| native americans| multiracial|united-states| overweight| adolescents| insurance| american| trends| prevalence| obesity| weight| impact.	FEB-2008	disparities| minorities| children| race| ethnicity| african americans| hispanics| asians/pacific islanders| native americans| multiracial|united-states| overweight| adolescents| insurance| american| trends| prevalence| obesity| weight| impact	Flores, G; Tomany-Korman, SC	Racial and ethnic disparities in medical and dental health, access to care, and use of services in US children		PEDIATRICS	disparities; minorities; children; race; ethnicity; African Americans; Hispanics; Asians/Pacific islanders; native Americans; multiracial	UNITED-STATES; OVERWEIGHT; ADOLESCENTS; INSURANCE; AMERICAN; TRENDS; PREVALENCE; OBESITY; WEIGHT; IMPACT	BACKGROUND. Not enough is known about the national prevalence of racial/ethnic disparities in children's medical and dental care. OBJECTIVE. The purpose of this work was to examine racial/ethnic disparities in medical and oral health, access to care, and use of services in a national sample. METHODS. The National Survey of Children's Health was a telephone survey in 2003 2004 of a national random sample of parents and guardians of 102 353 children 0 to 17 years old. Disparities in selected medical and oral health and health care measures were examined for white, African American, Latino, Asian/Pacific Islander, Native American, and multiracial children. Multivariate analyses were performed to adjust for primary language at home, age, insurance coverage, income, parental education and employment, and number of children and adults in the household. Forty measures of medical and oral health status, access to care, and use of services were analyzed. RESULTS. Many significant disparities were noted; for example, uninsurance rates were 6% for whites, 21% for Latinos, 15% for Native Americans, 7% for African Americans, and 4% for Asians or Pacific Islanders, and the proportions with a usual source of care were as follows: whites, 90%; Native Americans, 61%; Latinos, 68%; African Americans, 77%; and Asians or Pacific Islanders, 87%. Many disparities persisted for >= 1 minority group in multivariate analyses, including increased odds of suboptimal health status, overweight, asthma, activity limitations, behavioral and speech problems, emotional difficulties, uninsurance, suboptimal dental health, no usual source of care, unmet medical and dental needs, transportation barriers to care, problems getting specialty care, no medical or dental visit in the past year, emergency department visits, not receiving mental health care, and not receiving prescription medications. Certain disparities were particularly marked for specific racial/ethnic groups: for Latinos, suboptimal health status and teeth condition, uninsurance, and problems getting specialty care; for African Americans, asthma, behavior problems, skin allergies, speech problems, and unmet prescription needs; for Native Americans, hearing or vision problems, no usual source of care, emergency department visits, and unmet medical and dental needs; and for Asians or Pacific Islanders, problems getting specialty care and not seeing a doctor in the past year. Multiracial children also experienced many disparities. CONCLUSIONS. Minority children experience multiple disparities in medical and oral health, access to care, and use of services. Certain disparities are particularly marked for specific racial/ethnic groups, and multiracial children experience many disparities.	35	188	2008	13	10.1542/peds.2007-1243	Pediatrics
Epidemiologic evidence of relationships between reproductive and child health outcomes and environmental chemical contaminants. This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory and other childhood diseases, neuropsychological deficits, premature or delayed sexual maturation, and certain adult cancers linked to fetal or childhood exposures. Environmental exposures considered here include chemical toxicants in air, water, soil/house dust and foods (including human breast milk), and consumer products. Reports reviewed here included original epidemiologic studies (with at least basic descriptions of methods and results), literature reviews, expert group reports, meta-analyses, and pooled analyses. Levels of evidence for causal relationships were categorized as sufficient, limited, or inadequate according to predefined criteria. There was sufficient epidemiological evidence for causal relationships between several adverse pregnancy or child health outcomes and prenatal or childhood exposure to environmental chemical contaminants. These included prenatal high-level methylmercury (CH3Hg) exposure (delayed developmental milestones and cognitive, motor, auditory, and visual deficits), high-level prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related toxicants (neonatal tooth abnormalities, cognitive and motor deficits), maternal active smoking (delayed conception, preterm birth, fetal growth deficit [FGD] and sudden infant death syndrome [SIDS]) and prenatal environmental tobacco smoke (ETS) exposure (preterm birth), low-level childhood lead exposure (cognitive deficits and renal tubular damage), high-level childhood CH3Hg exposure (visual deficits), high-level childhood exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (chloracne), childhood ETS exposure (SIDS, new-onset asthma, increased asthma severity, lung and middle ear infections, and adult breast and lung cancer), childhood exposure to biomass smoke (lung infections), and childhood exposure to outdoor air pollutants (increased asthma severity). Evidence for some proven relationships came from investigation of relatively small numbers of children with high-dose prenatal or early childhood exposures, e. g., CH3Hg poisoning episodes in Japan and Iraq. In contrast, consensus on a causal relationship between incident asthma and ETS exposure came only recently after many studies and prolonged debate. There were many relationships supported by limited epidemiologic evidence, ranging from several studies with fairly consistent findings and evidence of dose-response relationships to those where 20 or more studies provided inconsistent or otherwise less than convincing evidence of an association. The latter included childhood cancer and parental or childhood exposures to pesticides. In most cases, relationships supported by inadequate epidemiologic evidence reflect scarcity of evidence as opposed to strong evidence of no effect. This summary points to three main needs: (1) Where relationships between child health and environmental exposures are supported by sufficient evidence of causal relationships, there is a need for (a) policies and programs to minimize population exposures and (b) population-based biomonitoring to track exposure levels, i.e., through ongoing or periodic surveys with measurements of contaminant levels in blood, urine and other samples. (2) For relationships suported by limited evidence, there is a need for targeted research and policy options ranging from ongoing evaluation of evidence to proactive actions. (3) There is a great need for population-based, multidisciplinary and collaborative research on the many relationships supported by inadequate evidence, as these represent major knowledge gaps. Expert groups faced with evaluating epidemiologic evidence of potential causal relationships repeatedly encounter problems in summarizing the available data. A major driver for undertaking such summaries is the need to compensate for the limited sample sizes of individual epidemiologic studies. Sample size limitations are major obstacles to exploration of prenatal, paternal, and childhood exposures during specific time windows, exposure intensity, exposure-exposure or exposure-gene interactions, and relatively rare health outcomes such as childhood cancer. Such research needs call for investments in research infrastructure, including human resources and methods development (standardized protocols, biomarker research, validated exposure metrics, reference analytic laboratories). These are needed to generate research findings that can be compared and subjected to pooled analyses aimed at knowledge synthesis.. level lead-exposure| adverse pregnancy outcomes| low-birth-weight| paternal occupational-exposure| in-utero exposure| neural-tube defects| hazardous-waste landfill| port-pirie cohort| acute lymphoblastic-leukemia| tobacco-smoke exposure.	2008	level lead-exposure| adverse pregnancy outcomes| low-birth-weight| paternal occupational-exposure| in-utero exposure| neural-tube defects| hazardous-waste landfill| port-pirie cohort| acute lymphoblastic-leukemia| tobacco-smoke exposure	Wigle, DT; Arbuckle, TE; Turner, MC; Berube, A; Yang, QY; Liu, SL; Krewski, D	Epidemiologic evidence of relationships between reproductive and child health outcomes and environmental chemical contaminants		JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS		LEVEL LEAD-EXPOSURE; ADVERSE PREGNANCY OUTCOMES; LOW-BIRTH-WEIGHT; PATERNAL OCCUPATIONAL-EXPOSURE; IN-UTERO EXPOSURE; NEURAL-TUBE DEFECTS; HAZARDOUS-WASTE LANDFILL; PORT-PIRIE COHORT; ACUTE LYMPHOBLASTIC-LEUKEMIA; TOBACCO-SMOKE EXPOSURE	This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory and other childhood diseases, neuropsychological deficits, premature or delayed sexual maturation, and certain adult cancers linked to fetal or childhood exposures. Environmental exposures considered here include chemical toxicants in air, water, soil/house dust and foods (including human breast milk), and consumer products. Reports reviewed here included original epidemiologic studies (with at least basic descriptions of methods and results), literature reviews, expert group reports, meta-analyses, and pooled analyses. Levels of evidence for causal relationships were categorized as sufficient, limited, or inadequate according to predefined criteria. There was sufficient epidemiological evidence for causal relationships between several adverse pregnancy or child health outcomes and prenatal or childhood exposure to environmental chemical contaminants. These included prenatal high-level methylmercury (CH3Hg) exposure (delayed developmental milestones and cognitive, motor, auditory, and visual deficits), high-level prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related toxicants (neonatal tooth abnormalities, cognitive and motor deficits), maternal active smoking (delayed conception, preterm birth, fetal growth deficit [FGD] and sudden infant death syndrome [SIDS]) and prenatal environmental tobacco smoke (ETS) exposure (preterm birth), low-level childhood lead exposure (cognitive deficits and renal tubular damage), high-level childhood CH3Hg exposure (visual deficits), high-level childhood exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (chloracne), childhood ETS exposure (SIDS, new-onset asthma, increased asthma severity, lung and middle ear infections, and adult breast and lung cancer), childhood exposure to biomass smoke (lung infections), and childhood exposure to outdoor air pollutants (increased asthma severity). Evidence for some proven relationships came from investigation of relatively small numbers of children with high-dose prenatal or early childhood exposures, e. g., CH3Hg poisoning episodes in Japan and Iraq. In contrast, consensus on a causal relationship between incident asthma and ETS exposure came only recently after many studies and prolonged debate. There were many relationships supported by limited epidemiologic evidence, ranging from several studies with fairly consistent findings and evidence of dose-response relationships to those where 20 or more studies provided inconsistent or otherwise less than convincing evidence of an association. The latter included childhood cancer and parental or childhood exposures to pesticides. In most cases, relationships supported by inadequate epidemiologic evidence reflect scarcity of evidence as opposed to strong evidence of no effect. This summary points to three main needs: (1) Where relationships between child health and environmental exposures are supported by sufficient evidence of causal relationships, there is a need for (a) policies and programs to minimize population exposures and (b) population-based biomonitoring to track exposure levels, i.e., through ongoing or periodic surveys with measurements of contaminant levels in blood, urine and other samples. (2) For relationships suported by limited evidence, there is a need for targeted research and policy options ranging from ongoing evaluation of evidence to proactive actions. (3) There is a great need for population-based, multidisciplinary and collaborative research on the many relationships supported by inadequate evidence, as these represent major knowledge gaps. Expert groups faced with evaluating epidemiologic evidence of potential causal relationships repeatedly encounter problems in summarizing the available data. A major driver for undertaking such summaries is the need to compensate for the limited sample sizes of individual epidemiologic studies. Sample size limitations are major obstacles to exploration of prenatal, paternal, and childhood exposures during specific time windows, exposure intensity, exposure-exposure or exposure-gene interactions, and relatively rare health outcomes such as childhood cancer. Such research needs call for investments in research infrastructure, including human resources and methods development (standardized protocols, biomarker research, validated exposure metrics, reference analytic laboratories). These are needed to generate research findings that can be compared and subjected to pooled analyses aimed at knowledge synthesis.	851	188	2008	145	10.1080/10937400801921320	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
An electronic nose in the discrimination of patients with asthma and controls. Background: Exhaled breath contains thousands of volatile organic compounds (VOCs) that could serve as biomarkers of lung disease. Electronic noses can distinguish VOC mixtures by pattern recognition. Objective: We hypothesized that an electronic nose can discriminate exhaled air of patients with asthma from healthy controls, and between patients with different disease severities. Methods: Ten young patients with mild asthma (25.1 +/- 5.9 years; FEV1, 99.9 +/- 7.7% predicted), 10 young controls (26.8 +/- 6.4 years; FEV1, 101.9 +/- 10.3), 10 older patients with severe asthma (49.5 +/- 12.0 years; FEV1, 62.3 +/- 23.6), and 10 older controls (57.3 +/- 7.1 years; FEV1, 108.3 +/- 14.7) joined a cross-sectional study with duplicate sampling of exhaled breath with an interval of 2 to 5 minutes. Subjects inspired VOC-filtered air by tidal breathing for 5 minutes, and a single expiratory vital capacity was collected into a Tedlar bag that was sampled by electronic nose (Cyranose 320) within 10 minutes. Smellprints were analyzed by linear discriminant analysis on principal component reduction. Cross-validation values (CVVs) were calculated. Results: Smellprints of patients with mild asthma were fully separated from young controls (CVV, 100%; Mahalanobis distance [M-distance], 5.32), and patients with severe asthma could be distinguished from old controls (CVV, 90%; M-distance, 2.77). Patients with mild and severe asthma could be less well discriminated (CVV, 65%; M-distance, 1.23), whereas the 2 control groups were indistinguishable (CVV, 50%; M-distance, 1.56). The duplicate samples replicated these results. Conclusion: An electronic nose can discriminate exhaled breath of patients with asthma from controls but is less accurate in distinguishing asthma severities. Clinical implication: These findings warrant validation of electronic noses in diagnosing newly presented patients with asthma.. asthma mild| asthma severe| biomarkers| diagnosis| electronic nose| exhaled breath| volatile organic compounds|volatile organic-compounds| composite vapor detectors| lung-cancer| exhaled breath| clinical-application| pulmonary-disease| markers| technology| pneumonia| diagnosis.	OCT-2007	asthma mild| asthma severe| biomarkers| diagnosis| electronic nose| exhaled breath| volatile organic compounds|volatile organic-compounds| composite vapor detectors| lung-cancer| exhaled breath| clinical-application| pulmonary-disease| markers| technology| pneumonia| diagnosis	Dragonieri, S; Schot, R; Mertens, BJA; Le Cessie, S; Gauw, SA; Spanevello, A; Resta, O; Willard, NP; Vink, TJ; Rabe, KF; Bel, EH; Sterk, PJ	An electronic nose in the discrimination of patients with asthma and controls		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma mild; asthma severe; biomarkers; diagnosis; electronic nose; exhaled breath; volatile organic compounds	VOLATILE ORGANIC-COMPOUNDS; COMPOSITE VAPOR DETECTORS; LUNG-CANCER; EXHALED BREATH; CLINICAL-APPLICATION; PULMONARY-DISEASE; MARKERS; TECHNOLOGY; PNEUMONIA; DIAGNOSIS	Background: Exhaled breath contains thousands of volatile organic compounds (VOCs) that could serve as biomarkers of lung disease. Electronic noses can distinguish VOC mixtures by pattern recognition. Objective: We hypothesized that an electronic nose can discriminate exhaled air of patients with asthma from healthy controls, and between patients with different disease severities. Methods: Ten young patients with mild asthma (25.1 +/- 5.9 years; FEV1, 99.9 +/- 7.7% predicted), 10 young controls (26.8 +/- 6.4 years; FEV1, 101.9 +/- 10.3), 10 older patients with severe asthma (49.5 +/- 12.0 years; FEV1, 62.3 +/- 23.6), and 10 older controls (57.3 +/- 7.1 years; FEV1, 108.3 +/- 14.7) joined a cross-sectional study with duplicate sampling of exhaled breath with an interval of 2 to 5 minutes. Subjects inspired VOC-filtered air by tidal breathing for 5 minutes, and a single expiratory vital capacity was collected into a Tedlar bag that was sampled by electronic nose (Cyranose 320) within 10 minutes. Smellprints were analyzed by linear discriminant analysis on principal component reduction. Cross-validation values (CVVs) were calculated. Results: Smellprints of patients with mild asthma were fully separated from young controls (CVV, 100%; Mahalanobis distance [M-distance], 5.32), and patients with severe asthma could be distinguished from old controls (CVV, 90%; M-distance, 2.77). Patients with mild and severe asthma could be less well discriminated (CVV, 65%; M-distance, 1.23), whereas the 2 control groups were indistinguishable (CVV, 50%; M-distance, 1.56). The duplicate samples replicated these results. Conclusion: An electronic nose can discriminate exhaled breath of patients with asthma from controls but is less accurate in distinguishing asthma severities. Clinical implication: These findings warrant validation of electronic noses in diagnosing newly presented patients with asthma.	35	188	2007	7	10.1016/j.jaci.2007.05.043	Allergy; Immunology
The Seattle-King County Healthy Homes Project: A randomized, controlled trial of a community health worker intervention to decrease exposure to indoor asthma triggers. Objectives. We assessed the effectiveness of a community health worker intervention focused on reducing exposure to indoor asthma triggers. Methods. We conducted a randomized controlled trial with 1-year follow-up among 274 low-income households containing a child aged 4-12 years who had asthma. Community health workers provided in-home environmental assessments, education, support for behavior change, and resources. Participants were assigned to either a high-intensity group receiving 7 visits and a full set of resources or a low-intensity group receiving a single visit and limited resources. Results. The high-intensity group improved significantly more than the low-intensity group in its pediatric asthma caregiver quality-of-life score (P=.005) and asthma-related urgent health services use (P=.026). Asthma symptom days declined more in the high-intensity group, although the across-group difference did not reach statistical significance (P=.138). Participant actions to reduce triggers generally increased in the high-intensity group. The projected 4-year net savings per participant among the high-intensity group relative to the low-intensity group were $189-$721. Conclusions. Community health workers reduced asthma symptom days and urgent health services use while improving caregiver quality-of-life score. Improvement was greater with a higher-intensity intervention.. low-income children| inner-city children| quality-of-life| urban children| mite allergen| cost| care| outreach| program| avoidance.	APR-2005	low-income children| inner-city children| quality-of-life| urban children| mite allergen| cost| care| outreach| program| avoidance	Krieger, JW; Takaro, TK; Song, L; Weaver, M	The Seattle-King County Healthy Homes Project: A randomized, controlled trial of a community health worker intervention to decrease exposure to indoor asthma triggers		AMERICAN JOURNAL OF PUBLIC HEALTH		LOW-INCOME CHILDREN; INNER-CITY CHILDREN; QUALITY-OF-LIFE; URBAN CHILDREN; MITE ALLERGEN; COST; CARE; OUTREACH; PROGRAM; AVOIDANCE	Objectives. We assessed the effectiveness of a community health worker intervention focused on reducing exposure to indoor asthma triggers. Methods. We conducted a randomized controlled trial with 1-year follow-up among 274 low-income households containing a child aged 4-12 years who had asthma. Community health workers provided in-home environmental assessments, education, support for behavior change, and resources. Participants were assigned to either a high-intensity group receiving 7 visits and a full set of resources or a low-intensity group receiving a single visit and limited resources. Results. The high-intensity group improved significantly more than the low-intensity group in its pediatric asthma caregiver quality-of-life score (P=.005) and asthma-related urgent health services use (P=.026). Asthma symptom days declined more in the high-intensity group, although the across-group difference did not reach statistical significance (P=.138). Participant actions to reduce triggers generally increased in the high-intensity group. The projected 4-year net savings per participant among the high-intensity group relative to the low-intensity group were $189-$721. Conclusions. Community health workers reduced asthma symptom days and urgent health services use while improving caregiver quality-of-life score. Improvement was greater with a higher-intensity intervention.	52	188	2005	8	10.2105/AJPH.2004.042994	Public, Environmental & Occupational Health
Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study. Background: Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed. Objective: To investigate the clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with placebo and to evaluate the relative clinical efficacy in relation to systemic side-effects. Methods: A 3-year randomized, placebo-controlled, double-blind, double-dummy study including 71 adult birch pollen hay fever patients treated for two consecutive years after a baseline year. Allocation to treatment groups was based on disease severity in the baseline season, gender and age. Results: Clinical efficacy was estimated in 58 patients completing the first treatment year by subtracting baseline data and by calculating the ratio first treatment season vs baseline. SLIT diminished the median disease severity to one-half and SCIT to one-third of placebo treatment. No statistical significant difference between the two groups was observed. Both for symptoms and medication scores actively treated patients showed statistically significant and clinical relevant efficacy compared with placebo. SLIT treatment only resulted in local mild side-effects, while SCIT resulted in few serious systemic side-effects. Conclusion: Based on the limited number of patients the clinical efficacy of SLIT was not statistically different from SCIT, and both treatments are clinically effective compared with placebo in the treatment of birch pollen rhinoconjunctivitis. The lack of significant difference between the two treatments does not indicate equivalent efficacy, but to detect minor differences necessitates investigation of larger groups. Due to the advantageous safety profile SLIT may be favored.. allergen-specific immunotherapy| clinical efficacy| controlled study| randomized| rhinitis| side-effects| subcutaneous| sublingual|house-dust-mite| standardized 5-grass-pollen extract| parietaria-judaica extract| health survey sf-36| grass-pollen| swallow immunotherapy| controlled trial| oral immunotherapy| hay-fever| rhinitis.	JAN-2004	allergen-specific immunotherapy| clinical efficacy| controlled study| randomized| rhinitis| side-effects| subcutaneous| sublingual|house-dust-mite| standardized 5-grass-pollen extract| parietaria-judaica extract| health survey sf-36| grass-pollen| swallow immunotherapy| controlled trial| oral immunotherapy| hay-fever| rhinitis	Khinchi, MS; Poulsen, LK; Carat, F; Andre, C; Hansen, AB; Malling, HJ	Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study		ALLERGY	allergen-specific immunotherapy; clinical efficacy; controlled study; randomized; rhinitis; side-effects; subcutaneous; sublingual	HOUSE-DUST-MITE; STANDARDIZED 5-GRASS-POLLEN EXTRACT; PARIETARIA-JUDAICA EXTRACT; HEALTH SURVEY SF-36; GRASS-POLLEN; SWALLOW IMMUNOTHERAPY; CONTROLLED TRIAL; ORAL IMMUNOTHERAPY; HAY-FEVER; RHINITIS	Background: Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed. Objective: To investigate the clinical efficacy of SLIT vs SCIT and secondary to compare SLIT and SCIT with placebo and to evaluate the relative clinical efficacy in relation to systemic side-effects. Methods: A 3-year randomized, placebo-controlled, double-blind, double-dummy study including 71 adult birch pollen hay fever patients treated for two consecutive years after a baseline year. Allocation to treatment groups was based on disease severity in the baseline season, gender and age. Results: Clinical efficacy was estimated in 58 patients completing the first treatment year by subtracting baseline data and by calculating the ratio first treatment season vs baseline. SLIT diminished the median disease severity to one-half and SCIT to one-third of placebo treatment. No statistical significant difference between the two groups was observed. Both for symptoms and medication scores actively treated patients showed statistically significant and clinical relevant efficacy compared with placebo. SLIT treatment only resulted in local mild side-effects, while SCIT resulted in few serious systemic side-effects. Conclusion: Based on the limited number of patients the clinical efficacy of SLIT was not statistically different from SCIT, and both treatments are clinically effective compared with placebo in the treatment of birch pollen rhinoconjunctivitis. The lack of significant difference between the two treatments does not indicate equivalent efficacy, but to detect minor differences necessitates investigation of larger groups. Due to the advantageous safety profile SLIT may be favored.	54	188	2004	9	10.1046/j.1398-9995.2003.00387.x	Allergy; Immunology
Self-reported symptoms and exercise-induced asthma in the elite athlete. Purpose: The purpose of this study was to compare self-reported symptoms for exercise-induced asthma (EIA) to postexercise challenge pulmonary function test results in elite athletes. Methods: Elite athletes (N = 158; 83 men and 75 women; age: 22 +/- 4.4 yr) performed pre- and post-exercise spirometry and were grouped according to postexercise pulmonary function decrements (PFT-positive, PFT-borderline. and PFT-normal for EIA). Before the sport/environment specific exercise challenge, subjects completed an EIA symptoms-specific questionnaire. Results: Resting FEV1 values were above predicted values (114-121%) and not different between groups. Twenty-six percent of the study population demonstrated >10% postexercise drop in FEV1 and 29% reported two or more symptoms. However, the proportion of PFT-positive and PFT-normal athletes reporting two or more symptoms was nor different (39% vs. 41%). Postrace cough was the most reported symptom, reported significantly more frequently for PFT-positive athletes (P < 0.05). Sensitivity/specificity analysis demonstrated a lack of effectiveness of self-reported symptoms to identify PFT-positive or exclude PFT-normal athletes. Postexercise lower limit reference ranges (MN-2SDs) were determined from normal athletes for FEV1, FEF25-75% and PEF to be -7%, -12.5%, and -18%, respectively. Conclusion: Although questionnaires provide reasonable estimates of ELA prevalence among elite cold-weather athletes, the use of self-reported symptoms for EIA diagnosis in this population will likely yield high frequencies Of both false positive and false negative results. Diagnosis should include spirometry using an exercise/environment specific challenge in combination with the athlete's history of asthma symptoms.. bronchospasm| cold weather| exercise-induced asthma| exercise| pulmonary function|cross-country skiers| induced bronchospasm| airway responsiveness| figure skaters| cold-air| challenge| children| runners| adults.	FEB-2001	bronchospasm| cold weather| exercise-induced asthma| exercise| pulmonary function|cross-country skiers| induced bronchospasm| airway responsiveness| figure skaters| cold-air| challenge| children| runners| adults	Rundell, KW; Im, JH; Mayers, LB; Wilber, RL; Szmedra, L; Schmitz, HR	Self-reported symptoms and exercise-induced asthma in the elite athlete		MEDICINE AND SCIENCE IN SPORTS AND EXERCISE	bronchospasm; cold weather; exercise-induced asthma; exercise; pulmonary function	CROSS-COUNTRY SKIERS; INDUCED BRONCHOSPASM; AIRWAY RESPONSIVENESS; FIGURE SKATERS; COLD-AIR; CHALLENGE; CHILDREN; RUNNERS; ADULTS	Purpose: The purpose of this study was to compare self-reported symptoms for exercise-induced asthma (EIA) to postexercise challenge pulmonary function test results in elite athletes. Methods: Elite athletes (N = 158; 83 men and 75 women; age: 22 +/- 4.4 yr) performed pre- and post-exercise spirometry and were grouped according to postexercise pulmonary function decrements (PFT-positive, PFT-borderline. and PFT-normal for EIA). Before the sport/environment specific exercise challenge, subjects completed an EIA symptoms-specific questionnaire. Results: Resting FEV1 values were above predicted values (114-121%) and not different between groups. Twenty-six percent of the study population demonstrated >10% postexercise drop in FEV1 and 29% reported two or more symptoms. However, the proportion of PFT-positive and PFT-normal athletes reporting two or more symptoms was nor different (39% vs. 41%). Postrace cough was the most reported symptom, reported significantly more frequently for PFT-positive athletes (P < 0.05). Sensitivity/specificity analysis demonstrated a lack of effectiveness of self-reported symptoms to identify PFT-positive or exclude PFT-normal athletes. Postexercise lower limit reference ranges (MN-2SDs) were determined from normal athletes for FEV1, FEF25-75% and PEF to be -7%, -12.5%, and -18%, respectively. Conclusion: Although questionnaires provide reasonable estimates of ELA prevalence among elite cold-weather athletes, the use of self-reported symptoms for EIA diagnosis in this population will likely yield high frequencies Of both false positive and false negative results. Diagnosis should include spirometry using an exercise/environment specific challenge in combination with the athlete's history of asthma symptoms.	32	188	2001	6		Sport Sciences
Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. Background: Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective: We sought to determine whether IgE antibodies to alpha-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods: Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results: Twenty-four patients with IgE antibodies to alpha-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow's milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for alpha-gal. Conclusion: We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope alpha-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb. (J Allergy Clin Immunol 2009;123:426-33.). anaphylaxis| urticaria| food allergy| galactose-alpha-1,3-galactose| cross-reactive carbohydrate determinant|cross-reactive ige| alpha-gal epitope| clinical-relevance| carbohydrate determinants| linked oligosaccharides| immunoglobulin-e| food allergy| solid-phase| glycoproteins| cetuximab.	FEB-2009	anaphylaxis| urticaria| food allergy| galactose-alpha-1,3-galactose| cross-reactive carbohydrate determinant|cross-reactive ige| alpha-gal epitope| clinical-relevance| carbohydrate determinants| linked oligosaccharides| immunoglobulin-e| food allergy| solid-phase| glycoproteins| cetuximab	Commins, SP; Satinover, SM; Hosen, J; Mozena, J; Borish, L; Lewis, BD; Woodfolk, JA; Platts-Mills, TAE	Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Anaphylaxis; urticaria; food allergy; galactose-alpha-1,3-galactose; cross-reactive carbohydrate determinant	CROSS-REACTIVE IGE; ALPHA-GAL EPITOPE; CLINICAL-RELEVANCE; CARBOHYDRATE DETERMINANTS; LINKED OLIGOSACCHARIDES; IMMUNOGLOBULIN-E; FOOD ALLERGY; SOLID-PHASE; GLYCOPROTEINS; CETUXIMAB	Background: Carbohydrate moieties are frequently encountered in food and can elicit IgE responses, the clinical significance of which has been unclear. Recent work, however, has shown that IgE antibodies to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate commonly expressed on nonprimate mammalian proteins, are capable of eliciting serious, even fatal, reactions. Objective: We sought to determine whether IgE antibodies to alpha-gal are present in sera from patients who report anaphylaxis or urticaria after eating beef, pork, or lamb. Methods: Detailed histories were taken from patients presenting to the University of Virginia Allergy Clinic. Skin prick tests (SPTs), intradermal skin tests, and serum IgE antibody analysis were performed for common indoor, outdoor, and food allergens. Results: Twenty-four patients with IgE antibodies to alpha-gal were identified. These patients described a similar history of anaphylaxis or urticaria 3 to 6 hours after the ingestion of meat and reported fewer or no episodes when following an avoidance diet. SPTs to mammalian meat produced wheals of usually less than 4 mm, whereas intradermal or fresh-food SPTs provided larger and more consistent wheal responses. CAP-RAST testing revealed specific IgE antibodies to beef, pork, lamb, cow's milk, cat, and dog but not turkey, chicken, or fish. Absorption experiments indicated that this pattern of sensitivity was explained by an IgE antibody specific for alpha-gal. Conclusion: We report a novel and severe food allergy related to IgE antibodies to the carbohydrate epitope alpha-gal. These patients experience delayed symptoms of anaphylaxis, angioedema, or urticaria associated with eating beef, pork, or lamb. (J Allergy Clin Immunol 2009;123:426-33.)	34	187	2009	8	10.1016/j.jaci.2008.10.052	Allergy; Immunology
Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme. Background Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma. We studied 6-7-year-old children from Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) programme to investigate the association between paracetamol consumption and asthma. Methods As part of Phase Three of ISAAC, parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis, and eczema, and several risk factors, including the use of paracetamol for fever in the child's first year of life and the frequency of paracetamol use in the past 12 months. The primary outcome variable was the odds ratio (OR) of asthma symptoms in these children associated with the use of paracetamol for fever in the first year of life, as calculated by logistic regression. Findings 205 487 children aged 6-7 years from 73 centres in 31. countries were included in the analysis. In the multivariate analyses, use of paracetamol for fever in the first year of life was associated with an increased risk of asthma symptoms when aged 6-7 years (OR 1.46 [95% Cl 1.36-1.56]). Current use of paracetamol was associated with a dose-dependent increased risk of asthma symptoms (1.61 [1.46-1.77] and 3.23 [2.9]-3.60] for medium and high use vs no use, respectively). Use of paracetamol was similarly associated with the risk of severe asthma symptoms, with population-attributable risks between 22% and 38%. Paracetamol use, both in the first year of life and in children aged 6-7 years, was also associated with an increased risk of symptoms of rhinoconjunctivitis and eczema. Interpretation Use of paracetamol in the first year of life and in later childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood. Funding The BUPA Foundation, the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the New Zealand Lottery Board, Astra Zeneca New Zealand, and Glaxo Wellcome international Medical Affairs.. worldwide variations| allergic rhinoconjunctivitis| acetaminophen use| lung-function| early-life| drug-use| prevalence| symptoms| aspirin| ibuprofen.	SEP 20-2008	worldwide variations| allergic rhinoconjunctivitis| acetaminophen use| lung-function| early-life| drug-use| prevalence| symptoms| aspirin| ibuprofen	Beasley, R; Clayton, T; Crane, J; von Mutius, E; Lai, CKW; Montefort, S; Stewart, A	Association between paracetamol use in infancy and childhood, and risk of asthma, rhinoconjunctivitis, and eczema in children aged 6-7 years: analysis from Phase Three of the ISAAC programme		LANCET		WORLDWIDE VARIATIONS; ALLERGIC RHINOCONJUNCTIVITIS; ACETAMINOPHEN USE; LUNG-FUNCTION; EARLY-LIFE; DRUG-USE; PREVALENCE; SYMPTOMS; ASPIRIN; IBUPROFEN	Background Exposure to paracetamol during intrauterine life, childhood, and adult life may increase the risk of developing asthma. We studied 6-7-year-old children from Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) programme to investigate the association between paracetamol consumption and asthma. Methods As part of Phase Three of ISAAC, parents or guardians of children aged 6-7 years completed written questionnaires about symptoms of asthma, rhinoconjunctivitis, and eczema, and several risk factors, including the use of paracetamol for fever in the child's first year of life and the frequency of paracetamol use in the past 12 months. The primary outcome variable was the odds ratio (OR) of asthma symptoms in these children associated with the use of paracetamol for fever in the first year of life, as calculated by logistic regression. Findings 205 487 children aged 6-7 years from 73 centres in 31. countries were included in the analysis. In the multivariate analyses, use of paracetamol for fever in the first year of life was associated with an increased risk of asthma symptoms when aged 6-7 years (OR 1.46 [95% Cl 1.36-1.56]). Current use of paracetamol was associated with a dose-dependent increased risk of asthma symptoms (1.61 [1.46-1.77] and 3.23 [2.9]-3.60] for medium and high use vs no use, respectively). Use of paracetamol was similarly associated with the risk of severe asthma symptoms, with population-attributable risks between 22% and 38%. Paracetamol use, both in the first year of life and in children aged 6-7 years, was also associated with an increased risk of symptoms of rhinoconjunctivitis and eczema. Interpretation Use of paracetamol in the first year of life and in later childhood, is associated with risk of asthma, rhinoconjunctivitis, and eczema at age 6 to 7 years. We suggest that exposure to paracetamol might be a risk factor for the development of asthma in childhood. Funding The BUPA Foundation, the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the New Zealand Lottery Board, Astra Zeneca New Zealand, and Glaxo Wellcome international Medical Affairs.	54	187	2008	10	10.1016/S0140-6736(08)61445-2	General & Internal Medicine
Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study. Background Subcutaneous immunotherapy for respiratory allergy has shown a long-lasting efficacy after its discontinuation, whereas this evidence is still lacking for sublingual immunotherapy, despite the fact that it is widely used. Objective We aimed to evaluate whether a long-lasting effect of SLIT occurs, in a prospective parallel group controlled study. Methods Sixty children (mean age 8.5 years) suffering from allergic asthma/rhinitis due to mites were subdivided into two matched groups: 35 underwent a 4- to 5-year course of SLIT with standardized extract and 25 received only drug therapy. The patients were evaluated at three time points (baseline, end of SLIT and 4 to 5 years after SLIT discontinuation) regarding presence of asthma, use of anti-asthma drugs, skin prick tests and specific IgE. Results We found that in the SLIT group there was a significant difference vs. baseline for the presence of asthma (P less than or equal to 0.001) and the use of asthma medications (P less than or equal to 0.01), whereas no difference was observed in the control group. The mean peak expiratory flow result was significantly higher in the active group than in the control group after 10 years. No change was seen as far as new sensitizations were concerned. Specific IgE showed a near-significant increase (baseline vs. 10 years, P = 0.06) only in the control group. Conclusion Our study demonstrates that sublingual immunotherapy is effective in children and that it maintains the clinical efficacy for 4 to 5 years after discontinuation.. asthma| children| long-lasting effect| respiratory allergy| rhinitis| sublingual immunotherapy|grass-pollen immunotherapy| double-blind| swallow immunotherapy| controlled trial| allergoid immunotherapy| messenger-rna| follow-up| placebo| rhinitis| sensitizations.	FEB-2003	asthma| children| long-lasting effect| respiratory allergy| rhinitis| sublingual immunotherapy|grass-pollen immunotherapy| double-blind| swallow immunotherapy| controlled trial| allergoid immunotherapy| messenger-rna| follow-up| placebo| rhinitis| sensitizations	Di Rienzo, V; Marcucci, F; Puccinelli, P; Parmiani, S; Frati, F; Sensi, L; Canonica, GW; Passalacqua, G	Long-lasting effect of sublingual immunotherapy in children with asthma due to house dust mite: a 10-year prospective study		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; children; long-lasting effect; respiratory allergy; rhinitis; sublingual immunotherapy	GRASS-POLLEN IMMUNOTHERAPY; DOUBLE-BLIND; SWALLOW IMMUNOTHERAPY; CONTROLLED TRIAL; ALLERGOID IMMUNOTHERAPY; MESSENGER-RNA; FOLLOW-UP; PLACEBO; RHINITIS; SENSITIZATIONS	Background Subcutaneous immunotherapy for respiratory allergy has shown a long-lasting efficacy after its discontinuation, whereas this evidence is still lacking for sublingual immunotherapy, despite the fact that it is widely used. Objective We aimed to evaluate whether a long-lasting effect of SLIT occurs, in a prospective parallel group controlled study. Methods Sixty children (mean age 8.5 years) suffering from allergic asthma/rhinitis due to mites were subdivided into two matched groups: 35 underwent a 4- to 5-year course of SLIT with standardized extract and 25 received only drug therapy. The patients were evaluated at three time points (baseline, end of SLIT and 4 to 5 years after SLIT discontinuation) regarding presence of asthma, use of anti-asthma drugs, skin prick tests and specific IgE. Results We found that in the SLIT group there was a significant difference vs. baseline for the presence of asthma (P less than or equal to 0.001) and the use of asthma medications (P less than or equal to 0.01), whereas no difference was observed in the control group. The mean peak expiratory flow result was significantly higher in the active group than in the control group after 10 years. No change was seen as far as new sensitizations were concerned. Specific IgE showed a near-significant increase (baseline vs. 10 years, P = 0.06) only in the control group. Conclusion Our study demonstrates that sublingual immunotherapy is effective in children and that it maintains the clinical efficacy for 4 to 5 years after discontinuation.	31	187	2003	5	10.1046/j.1365-2222.2003.01587.x	Allergy; Immunology
Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives. Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. (C) 2013 Elsevier Inc. All rights reserved.. pesticides| systematic review| chronic diseases| cancer| birth defects| reproductive toxicity| parkinson| alzheimer| amyotrophic lateral sclerosis| diabetes| asthma| cardiovascular disease| nephropathy| genetic damage| epigenetics| endocrine disruption| mitochondrial dysfunction| oxidative stress| endoplasmic reticulum stress| proteotoxicity|non-hodgkins-lymphoma| amyotrophic-lateral-sclerosis| endoplasmic-reticulum stress| environmental risk-factors| sister-chromatid exchanges| soft-tissue sarcoma| epigenetic transgenerational actions| parental occupational-exposure| persistent organic pollutants| induced oxidative stress.	APR 15-2013	pesticides| systematic review| chronic diseases| cancer| birth defects| reproductive toxicity| parkinson| alzheimer| amyotrophic lateral sclerosis| diabetes| asthma| cardiovascular disease| nephropathy| genetic damage| epigenetics| endocrine disruption| mitochondrial dysfunction| oxidative stress| endoplasmic reticulum stress| proteotoxicity|non-hodgkins-lymphoma| amyotrophic-lateral-sclerosis| endoplasmic-reticulum stress| environmental risk-factors| sister-chromatid exchanges| soft-tissue sarcoma| epigenetic transgenerational actions| parental occupational-exposure| persistent organic pollutants| induced oxidative stress	Mostafalou, S; Abdollahi, M	Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives		TOXICOLOGY AND APPLIED PHARMACOLOGY	Pesticides; Systematic review; Chronic diseases; Cancer; Birth defects; Reproductive toxicity; Parkinson; Alzheimer; Amyotrophic lateral sclerosis; Diabetes; Asthma; Cardiovascular disease; Nephropathy; Genetic damage; Epigenetics; Endocrine disruption; Mitochondrial dysfunction; Oxidative stress; Endoplasmic reticulum stress; Proteotoxicity	NON-HODGKINS-LYMPHOMA; AMYOTROPHIC-LATERAL-SCLEROSIS; ENDOPLASMIC-RETICULUM STRESS; ENVIRONMENTAL RISK-FACTORS; SISTER-CHROMATID EXCHANGES; SOFT-TISSUE SARCOMA; EPIGENETIC TRANSGENERATIONAL ACTIONS; PARENTAL OCCUPATIONAL-EXPOSURE; PERSISTENT ORGANIC POLLUTANTS; INDUCED OXIDATIVE STRESS	Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies, autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. (C) 2013 Elsevier Inc. All rights reserved.	476	186	2013	21	10.1016/j.taap.2013.01.025	Pharmacology & Pharmacy; Toxicology
Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Background: Less microbial exposure in early childhood is associated with more allergic disease later. Allergic children have a different fecal microflora, with less lactobacilli and bifidobacteria. Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation. Objective: We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies. Methods: In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months. Infants also received a prebiotic galactooligosaccharide or placebo. At 5 years, we evaluated the cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization. Results: Of the 1018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P = .035). Conclusions: No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children. It conferred protection only to cesarean-delivered children. (J Allergy Clin Immunol 2009;123:335-41.). allergy| prevention| high-risk infants| probiotic| prebiotic| eczema| allergic rhinitis| asthma| cesarean|placebo-controlled trial| 1st 6 months| atopic-dermatitis| double-blind| intestinal microflora| eczema| infants| risk| life| oligosaccharides.	FEB-2009	allergy| prevention| high-risk infants| probiotic| prebiotic| eczema| allergic rhinitis| asthma| cesarean|placebo-controlled trial| 1st 6 months| atopic-dermatitis| double-blind| intestinal microflora| eczema| infants| risk| life| oligosaccharides	Kuitunen, M; Kukkonen, K; Juntunen-Backman, K; Korpela, R; Poussa, T; Tuure, T; Haahtela, T; Savilahti, E	Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergy; prevention; high-risk infants; probiotic; prebiotic; eczema; allergic rhinitis; asthma; cesarean	PLACEBO-CONTROLLED TRIAL; 1ST 6 MONTHS; ATOPIC-DERMATITIS; DOUBLE-BLIND; INTESTINAL MICROFLORA; ECZEMA; INFANTS; RISK; LIFE; OLIGOSACCHARIDES	Background: Less microbial exposure in early childhood is associated with more allergic disease later. Allergic children have a different fecal microflora, with less lactobacilli and bifidobacteria. Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation. Objective: We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies. Methods: In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months. Infants also received a prebiotic galactooligosaccharide or placebo. At 5 years, we evaluated the cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization. Results: Of the 1018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P = .035). Conclusions: No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children. It conferred protection only to cesarean-delivered children. (J Allergy Clin Immunol 2009;123:335-41.)	32	186	2009	7	10.1016/j.jaci.2008.11.019	Allergy; Immunology
The medical effects of mold exposure. Exposure to molds can cause human disease through several well-defined mechanisms. In addition, many new mold-related illnesses have been hypothesized in recent years that remain largely or completely unproved. Concerns about mold exposure and its effects are so common that all health care providers, particularly allergists and immunologists, are frequently faced with issues regarding these real and asserted mold-related illnesses. The purpose of this position paper is to provide a state-of-the-art review of the role that molds are known to play in human disease, including asthma, allergic rhinitis, allergic bronchopulmonary aspergillosis, sinusitis, and hypersensitivity pneumonitis. In addition, other purported mold-related illnesses and the data that currently exist to support them are carefully reviewed, as are the currently available approaches for the evaluation of both patients and the environment.. mold| fungi| hypersensitivity| allergy| asthma|atopic-dermatitis| fungal allergens| 1st year| symptoms| health| asthma| mycotoxins| risk| ige| spores.	FEB-2006	mold| fungi| hypersensitivity| allergy| asthma|atopic-dermatitis| fungal allergens| 1st year| symptoms| health| asthma| mycotoxins| risk| ige| spores	Bush, RK; Portnoy, JM; Saxon, A; Terr, AI; Wood, RA	The medical effects of mold exposure		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	mold; fungi; hypersensitivity; allergy; asthma	ATOPIC-DERMATITIS; FUNGAL ALLERGENS; 1ST YEAR; SYMPTOMS; HEALTH; ASTHMA; MYCOTOXINS; RISK; IGE; SPORES	Exposure to molds can cause human disease through several well-defined mechanisms. In addition, many new mold-related illnesses have been hypothesized in recent years that remain largely or completely unproved. Concerns about mold exposure and its effects are so common that all health care providers, particularly allergists and immunologists, are frequently faced with issues regarding these real and asserted mold-related illnesses. The purpose of this position paper is to provide a state-of-the-art review of the role that molds are known to play in human disease, including asthma, allergic rhinitis, allergic bronchopulmonary aspergillosis, sinusitis, and hypersensitivity pneumonitis. In addition, other purported mold-related illnesses and the data that currently exist to support them are carefully reviewed, as are the currently available approaches for the evaluation of both patients and the environment.	44	186	2006	8	10.1016/j.jaci.2005.12.001	Allergy; Immunology
Hay fever and asthma in relation to markers of infection in the United States. Background: The hygiene hypothesis proposes that declining exposure to infections is implicated in the rising trend of allergy, and asthma. Objective: We sought to test this hypothesis by examining the relationship of hay fever, asthma, and atopic sensitization with markers of infection in a large general population sample of the United States. Methods: We analyzed the data of 33,994 US residents recorded in a public database of a nationally representative cross-sectional survey (Third National Health and Nutrition Examination Survey, 1988-1994). The variables examined were sociodemographic information, lifetime diagnosis and age at first diagnosis of hay fever or asthma, current skin sensitization to 9 airborne allergens and peanut, and current serology for Toxoplasma gondii, herpes simplex viruses type 1 and 2, and hepatitis A, B, and C viruses. Results: Hay fever (adjusted odds ratio, 0.27; 95% CI, 0.18-0.41; P<.001) and asthma (adjusted odds ratio, 0.45; 95% CI, 0.31-0.66; P<.001) were less frequent in subjects seropositive for hepatitis A virus (HAV), T gondii, and herpes simplex virus 1 versus seronegative subjects after adjusting for age, sex, race, urban residence, census region, family size, income, an education. Skin sensitization to peanut and to all the airborne allergens examined, except for cockroach, was less frequent among HAV-seropositive versus HAV-seronegative subjects younger than 40 years of age. The prevalence of hay fever and asthma diagnosed at or before 18 years of age in HAV-seronegative subjects increased progressively from 2.7% (95% CI, 0.71%-4.7%) and 0.4% (95% CI, 0.1%-1.6%), respectively, in cohorts born before 1920 to 8.5% (95% CI, 7.3%-9.7%) and 5.8% (95% CI, 4.8%-6.8%), respectively, in cohorts born in the 1960s, whereas they remained constant at around 2% in all cohorts of HAV-seropositive subjects. Conclusion: In the United States serologic evidence of acquisition of certain infections, mainly food-borne and orofecal infection, is associated with a lower probability of having hay, fever and asthma. Third National Health and Nutrition Examination Survey data support the hypothesis that hygiene is a major factor contributing to the increase in hay fever, asthma, and atopic sensitization in westernized countries.. asthma| hay fever| hepatitis a virus| hygiene| infection| epidemiology| national health and nutrition examination survey iii|anthroposophic life-style| atopy| prevalence| children| childhood| siblings| exposure| increase| allergy| hygiene.	SEP-2002	asthma| hay fever| hepatitis a virus| hygiene| infection| epidemiology| national health and nutrition examination survey iii|anthroposophic life-style| atopy| prevalence| children| childhood| siblings| exposure| increase| allergy| hygiene	Matricardi, PM; Rosmini, F; Panetta, V; Ferrigno, L; Bonini, S	Hay fever and asthma in relation to markers of infection in the United States		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; hay fever; hepatitis A virus; hygiene; infection; epidemiology; National Health and Nutrition Examination Survey III	ANTHROPOSOPHIC LIFE-STYLE; ATOPY; PREVALENCE; CHILDREN; CHILDHOOD; SIBLINGS; EXPOSURE; INCREASE; ALLERGY; HYGIENE	Background: The hygiene hypothesis proposes that declining exposure to infections is implicated in the rising trend of allergy, and asthma. Objective: We sought to test this hypothesis by examining the relationship of hay fever, asthma, and atopic sensitization with markers of infection in a large general population sample of the United States. Methods: We analyzed the data of 33,994 US residents recorded in a public database of a nationally representative cross-sectional survey (Third National Health and Nutrition Examination Survey, 1988-1994). The variables examined were sociodemographic information, lifetime diagnosis and age at first diagnosis of hay fever or asthma, current skin sensitization to 9 airborne allergens and peanut, and current serology for Toxoplasma gondii, herpes simplex viruses type 1 and 2, and hepatitis A, B, and C viruses. Results: Hay fever (adjusted odds ratio, 0.27; 95% CI, 0.18-0.41; P<.001) and asthma (adjusted odds ratio, 0.45; 95% CI, 0.31-0.66; P<.001) were less frequent in subjects seropositive for hepatitis A virus (HAV), T gondii, and herpes simplex virus 1 versus seronegative subjects after adjusting for age, sex, race, urban residence, census region, family size, income, an education. Skin sensitization to peanut and to all the airborne allergens examined, except for cockroach, was less frequent among HAV-seropositive versus HAV-seronegative subjects younger than 40 years of age. The prevalence of hay fever and asthma diagnosed at or before 18 years of age in HAV-seronegative subjects increased progressively from 2.7% (95% CI, 0.71%-4.7%) and 0.4% (95% CI, 0.1%-1.6%), respectively, in cohorts born before 1920 to 8.5% (95% CI, 7.3%-9.7%) and 5.8% (95% CI, 4.8%-6.8%), respectively, in cohorts born in the 1960s, whereas they remained constant at around 2% in all cohorts of HAV-seropositive subjects. Conclusion: In the United States serologic evidence of acquisition of certain infections, mainly food-borne and orofecal infection, is associated with a lower probability of having hay, fever and asthma. Third National Health and Nutrition Examination Survey data support the hypothesis that hygiene is a major factor contributing to the increase in hay fever, asthma, and atopic sensitization in westernized countries.	29	186	2002	7	10.1067/mai.2002.126658	Allergy; Immunology
Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function. Background-Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development. Methods-A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by at self-administered questionnaire completed by parents of 4th,7th; and 10th grade students in 1993. Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics. Results-In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (-3.0%, 95% CI -4.4 to -1.4), mean mid expiratory flow (MMEF) (-4.6%, 95% CI -7.0 to -2.3), and forced expiratory flow (FEF75) (-6.2%, 95% CI -9.1 to -3.1), but not forced expiratory volume in one second (FEV1). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (-4.1%, 95% CI -7.6 to -0.4) and FEF75 (-4.4%, 95% CI -9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF75 associated with all measurements of ETS were substantially reduced and were not statistically significant. Conclusions-In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows.. maternal smoking| pregnancy| environmental tobacco smoke| lung function| children|pulmonary-function| parental smoking| function growth| children| asthma| life.	APR-2000	maternal smoking| pregnancy| environmental tobacco smoke| lung function| children|pulmonary-function| parental smoking| function growth| children| asthma| life	Gilliland, FD; Berhane, K; McConnell, R; Gauderman, WJ; Vora, H; Rappaport, EB; Avol, E; Peters, JM	Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function		THORAX	maternal smoking; pregnancy; environmental tobacco smoke; lung function; children	PULMONARY-FUNCTION; PARENTAL SMOKING; FUNCTION GROWTH; CHILDREN; ASTHMA; LIFE	Background-Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development. Methods-A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by at self-administered questionnaire completed by parents of 4th,7th; and 10th grade students in 1993. Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics. Results-In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (-3.0%, 95% CI -4.4 to -1.4), mean mid expiratory flow (MMEF) (-4.6%, 95% CI -7.0 to -2.3), and forced expiratory flow (FEF75) (-6.2%, 95% CI -9.1 to -3.1), but not forced expiratory volume in one second (FEV1). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (-4.1%, 95% CI -7.6 to -0.4) and FEF75 (-4.4%, 95% CI -9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF75 associated with all measurements of ETS were substantially reduced and were not statistically significant. Conclusions-In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows.	32	186	2000	6	10.1136/thorax.55.4.271	Respiratory System
Endotoxin exposure is a risk factor for asthma - The National Survey of Endotoxin in United States Housing. Background: Although research has shown that early life exposure to household endotoxin protects against development of allergies, studies are less clear on the relationship between household endotoxin exposure and prevalence of wheezing and asthma. We assayed 2,552 house dust samples in a representative nationwide sample to explore relationships between endotoxin exposures and risk factors for asthma, asthma symptoms, and medication use. Methods: House dust was vacuum-sampled from five locations within homes and assayed for endotoxin. Health, demographic, and housing information was assessed through questionnaire and on-site evaluation of 2,456 residents of 831 homes selected to represent the demographics of the United States. Results: Endotoxin concentration (EU/mg) and load (EU/m(2)) were highly correlated (r = 0.73-0.79). Geometric mean endotoxin concentrations were as follows (in EU/mg): bedroom floors, 35.3 (5th-95th percentile, 5.0-260); bedding, 18.7 (2.0-142); family room floors, 63.9 (11.5-331); sofas, 44.8 (6.4-240); and kitchen floors, 80.5 (9.8-512). Multivariate analysis demonstrated significant relationships between increasing endotoxin levels and diagnosed asthma, asthma symptoms in the past year, current use of asthma medications, and wheezing among residents of the homes. These relationships were strongest for bedroom floor and bedding dust and were observed in adults only. Modeling the joint effect of bedding and bedroom floor endotoxin on recent asthma symptoms yielded an adjusted odds ratio of 2.83 (95% confidence interval, 1.01-7.87). When stratified by allergy status, allergic subjects with higher endotoxin exposure were no more likely to have diagnosed asthma or asthma symptoms than nonallergic subjects. Conclusion: This study demonstrates that household endotoxin exposure is a significant risk factor for increased asthma prevalence.. airway inflammation| house dust| lipopolysaccharide| wheeze|lower respiratory-tract| dust-induced inflammation| grain dust| cotton dust| airborne endotoxin| allergic diseases| birth cohort| children| farm| lipopolysaccharide.	DEC 1-2005	airway inflammation| house dust| lipopolysaccharide| wheeze|lower respiratory-tract| dust-induced inflammation| grain dust| cotton dust| airborne endotoxin| allergic diseases| birth cohort| children| farm| lipopolysaccharide	Thorne, PS; Kulhankova, K; Yin, M; Cohn, R; Arbes, SJ; Zeldin, DC	Endotoxin exposure is a risk factor for asthma - The National Survey of Endotoxin in United States Housing		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	airway inflammation; house dust; lipopolysaccharide; wheeze	LOWER RESPIRATORY-TRACT; DUST-INDUCED INFLAMMATION; GRAIN DUST; COTTON DUST; AIRBORNE ENDOTOXIN; ALLERGIC DISEASES; BIRTH COHORT; CHILDREN; FARM; LIPOPOLYSACCHARIDE	Background: Although research has shown that early life exposure to household endotoxin protects against development of allergies, studies are less clear on the relationship between household endotoxin exposure and prevalence of wheezing and asthma. We assayed 2,552 house dust samples in a representative nationwide sample to explore relationships between endotoxin exposures and risk factors for asthma, asthma symptoms, and medication use. Methods: House dust was vacuum-sampled from five locations within homes and assayed for endotoxin. Health, demographic, and housing information was assessed through questionnaire and on-site evaluation of 2,456 residents of 831 homes selected to represent the demographics of the United States. Results: Endotoxin concentration (EU/mg) and load (EU/m(2)) were highly correlated (r = 0.73-0.79). Geometric mean endotoxin concentrations were as follows (in EU/mg): bedroom floors, 35.3 (5th-95th percentile, 5.0-260); bedding, 18.7 (2.0-142); family room floors, 63.9 (11.5-331); sofas, 44.8 (6.4-240); and kitchen floors, 80.5 (9.8-512). Multivariate analysis demonstrated significant relationships between increasing endotoxin levels and diagnosed asthma, asthma symptoms in the past year, current use of asthma medications, and wheezing among residents of the homes. These relationships were strongest for bedroom floor and bedding dust and were observed in adults only. Modeling the joint effect of bedding and bedroom floor endotoxin on recent asthma symptoms yielded an adjusted odds ratio of 2.83 (95% confidence interval, 1.01-7.87). When stratified by allergy status, allergic subjects with higher endotoxin exposure were no more likely to have diagnosed asthma or asthma symptoms than nonallergic subjects. Conclusion: This study demonstrates that household endotoxin exposure is a significant risk factor for increased asthma prevalence.	41	185	2005	7	10.1164/rccm.200505-758OC	General & Internal Medicine; Respiratory System
Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission. Background: Nitric oxide in exhaled air (FENO) is a marker of eosinophilic airway inflammation. A study was undertaken to determine whether FENO predicts asthma relapse in asymptomatic asthmatic children in whom inhaled corticosteroids are discontinued. Methods: Forty children ( 21 boys) of mean age 12.2 years on a median dose of 400 mg budesonide or equivalent ( range 100 - 400) were included. FENO was measured before and 2, 4, 12, and 24 weeks after withdrawal of steroids. A relapse was defined as more than one exacerbation per month, or need for beta agonist treatment on 4 days per week for at least 2 weeks, or diurnal peak flow variability of >20%. FENO measurements were performed online with an expiratory flow of 50 ml/s. Results: Nine patients relapsed. Two and 4 weeks after withdrawal of steroids geometric mean FENO in children who were about to relapse was higher than in those who did not relapse: 35.3 ppb v 15.7 ppb at 2 weeks ( ratio 2.3; 95% CI 1.2 to 4.1; p = 0.01) and 40.8 ppb v 15.9 ppb at 4 weeks ( ratio 2.6; 95% CI 1.3 to 5.1). An FENO value of 49 ppb at 4 weeks after discontinuation of steroids had the best combination of sensitivity ( 71%) and specificity ( 93%) for asthma relapse. Conclusion: FENO 2 and 4 weeks after discontinuation of steroids in asymptomatic asthmatic children may be an objective predictor of asthma relapse.. airway inflammation| inhaled budesonide| childhood asthma| mild asthma| markers| corticosteroids| reproducibility| beclomethasone| adults.	MAR-2005	airway inflammation| inhaled budesonide| childhood asthma| mild asthma| markers| corticosteroids| reproducibility| beclomethasone| adults	Pijnenburg, MW; Hofhuis, W; Hop, WC; De Jongste, JC	Exhaled nitric oxide predicts asthma relapse in children with clinical asthma remission		THORAX		AIRWAY INFLAMMATION; INHALED BUDESONIDE; CHILDHOOD ASTHMA; MILD ASTHMA; MARKERS; CORTICOSTEROIDS; REPRODUCIBILITY; BECLOMETHASONE; ADULTS	Background: Nitric oxide in exhaled air (FENO) is a marker of eosinophilic airway inflammation. A study was undertaken to determine whether FENO predicts asthma relapse in asymptomatic asthmatic children in whom inhaled corticosteroids are discontinued. Methods: Forty children ( 21 boys) of mean age 12.2 years on a median dose of 400 mg budesonide or equivalent ( range 100 - 400) were included. FENO was measured before and 2, 4, 12, and 24 weeks after withdrawal of steroids. A relapse was defined as more than one exacerbation per month, or need for beta agonist treatment on 4 days per week for at least 2 weeks, or diurnal peak flow variability of >20%. FENO measurements were performed online with an expiratory flow of 50 ml/s. Results: Nine patients relapsed. Two and 4 weeks after withdrawal of steroids geometric mean FENO in children who were about to relapse was higher than in those who did not relapse: 35.3 ppb v 15.7 ppb at 2 weeks ( ratio 2.3; 95% CI 1.2 to 4.1; p = 0.01) and 40.8 ppb v 15.9 ppb at 4 weeks ( ratio 2.6; 95% CI 1.3 to 5.1). An FENO value of 49 ppb at 4 weeks after discontinuation of steroids had the best combination of sensitivity ( 71%) and specificity ( 93%) for asthma relapse. Conclusion: FENO 2 and 4 weeks after discontinuation of steroids in asymptomatic asthmatic children may be an objective predictor of asthma relapse.	21	185	2005	4	10.1136/thx.2004.023374	Respiratory System
Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma. Background: Few studies have characterized the atopic profile of toddler-aged children with recurrent wheezing at high risk of the development of persistent asthma. Objective: We sought to determine the atopic profile of toddler-aged children with frequent wheeze at high risk for the development of persistent asthma who either had a parental history of asthma, a personal history of atopic dermatitis, or both. Methods: Participants enrolled in the Prevention of Early Asthma in Kids study (n = 285) on the basis of a modified Asthma Predictive Index were characterized on the basis of allergy and asthma questionnaire responses and allergy skin puncture test results. Results: The majority of the children (60.7%, n = 148) were sensitized to either food or aeroallergens. Male children were significantly more likely to be sensitized to aeroallergens (P =.03) and to have a blood eosinophil level of 4% or greater (P =.03) and a total serum IgE level of greater than 100 IU/mL (P =.0004). Additionally, eosinophilia and total serum IgE level had the strongest correlation with aeroallergen sensitization. Conclusion: The high prevalence of aeroallergen sensitization in this high-risk cohort suggests that aeroallergens might have an important role in the early development of asthma. As such, the Prevention of Early Asthma in Kids cohort appears to he an appropriate cohort in which to test whether early intervention with an inhaled corticosteroid can significantly attenuate, or perhaps even prevent, the allergic march from the initial stages of allergic sensitization to the subsequent development of asthma in toddlers with episodic wheezing.. allergens| aeroallergen and food sensitization| asthma predictive index| atopy| clinical trials| eariv childhood asthma| fluticasone| glucocorticoids| intermittent wheezing| prevention of asthma| research network| skin prick test|management program camp| inner-city asthma| house-dust mite| bronchial hyperresponsiveness| natural-history| ige antibodies| allergens| sensitization| exposure| design.	DEC-2004	allergens| aeroallergen and food sensitization| asthma predictive index| atopy| clinical trials| eariv childhood asthma| fluticasone| glucocorticoids| intermittent wheezing| prevention of asthma| research network| skin prick test|management program camp| inner-city asthma| house-dust mite| bronchial hyperresponsiveness| natural-history| ige antibodies| allergens| sensitization| exposure| design	Guilbert, TW; Morgan, WJ; Zeiger, RS; Bacharier, LB; Boehmer, SJ; Krawiec, M; Larsen, G; Lemanske, RF; Liu, A; Mauger, DT; Sorkness, C; Szefler, SJ; Strunk, RC; Taussig, LM; Martinez, FD	Atopic characteristics of children with recurrent wheezing at high risk for the development of childhood asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergens; aeroallergen and food sensitization; asthma predictive index; atopy; clinical trials; earIv childhood asthma; fluticasone; glucocorticoids; intermittent wheezing; prevention of asthma; research network; skin prick test	MANAGEMENT PROGRAM CAMP; INNER-CITY ASTHMA; HOUSE-DUST MITE; BRONCHIAL HYPERRESPONSIVENESS; NATURAL-HISTORY; IGE ANTIBODIES; ALLERGENS; SENSITIZATION; EXPOSURE; DESIGN	Background: Few studies have characterized the atopic profile of toddler-aged children with recurrent wheezing at high risk of the development of persistent asthma. Objective: We sought to determine the atopic profile of toddler-aged children with frequent wheeze at high risk for the development of persistent asthma who either had a parental history of asthma, a personal history of atopic dermatitis, or both. Methods: Participants enrolled in the Prevention of Early Asthma in Kids study (n = 285) on the basis of a modified Asthma Predictive Index were characterized on the basis of allergy and asthma questionnaire responses and allergy skin puncture test results. Results: The majority of the children (60.7%, n = 148) were sensitized to either food or aeroallergens. Male children were significantly more likely to be sensitized to aeroallergens (P =.03) and to have a blood eosinophil level of 4% or greater (P =.03) and a total serum IgE level of greater than 100 IU/mL (P =.0004). Additionally, eosinophilia and total serum IgE level had the strongest correlation with aeroallergen sensitization. Conclusion: The high prevalence of aeroallergen sensitization in this high-risk cohort suggests that aeroallergens might have an important role in the early development of asthma. As such, the Prevention of Early Asthma in Kids cohort appears to he an appropriate cohort in which to test whether early intervention with an inhaled corticosteroid can significantly attenuate, or perhaps even prevent, the allergic march from the initial stages of allergic sensitization to the subsequent development of asthma in toddlers with episodic wheezing.	39	185	2004	6	10.1016/j.jaci.2004.09.020	Allergy; Immunology
Living near a main road and the risk of wheezing illness in children. The effect of road vehicle traffic pollution on asthma is still not clearly understood. However, any effect is likely to be most marked among those who live within 150 m of a main road, because this is the distance within which concentrations of primary vehicle traffic pollutants are raised above ambient background levels. We have investigated the relation between proximity of the family home to the nearest main road, estimated objectively using geographical information system software, and the risk of wheeze in the past year in a case-control sample of 6,147 primary schoolchildren (age 4 to I I yr) and a random cross-sectional sample of 3,709 secondary schoolchildren (age I I to 16 yr) in Nottingham, United Kingdom. Among children living within 150 m of a main road, the risk of wheeze increased with increasing proximity by an odds ratio (OR) of 1.08 (95% confidence interval [CI] 1.00 to 1.16) per 30-m increment in primary schoolchildren, and 1.16 (1.02 to 1.32) in secondary schoolchildren. Most of the increased risk was localized to within 90 m of the roadside. Among primary schoolchildren, effects were stronger in girls than boys (P-interaction = 0.02). Living within approximately 90 m of a main road is associated with a proximity-related increase in the risk of wheezing illness in children.. asthma| wheezing| children| vehicular emissions|chronic respiratory symptoms| traffic density| air-pollution| asthma| prevalence| motorways| exposure| exhaust.	DEC 15-2001	asthma| wheezing| children| vehicular emissions|chronic respiratory symptoms| traffic density| air-pollution| asthma| prevalence| motorways| exposure| exhaust	Venn, AJ; Lewis, SA; Cooper, M; Hubbard, R; Britton, J	Living near a main road and the risk of wheezing illness in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; wheezing; children; vehicular emissions	CHRONIC RESPIRATORY SYMPTOMS; TRAFFIC DENSITY; AIR-POLLUTION; ASTHMA; PREVALENCE; MOTORWAYS; EXPOSURE; EXHAUST	The effect of road vehicle traffic pollution on asthma is still not clearly understood. However, any effect is likely to be most marked among those who live within 150 m of a main road, because this is the distance within which concentrations of primary vehicle traffic pollutants are raised above ambient background levels. We have investigated the relation between proximity of the family home to the nearest main road, estimated objectively using geographical information system software, and the risk of wheeze in the past year in a case-control sample of 6,147 primary schoolchildren (age 4 to I I yr) and a random cross-sectional sample of 3,709 secondary schoolchildren (age I I to 16 yr) in Nottingham, United Kingdom. Among children living within 150 m of a main road, the risk of wheeze increased with increasing proximity by an odds ratio (OR) of 1.08 (95% confidence interval [CI] 1.00 to 1.16) per 30-m increment in primary schoolchildren, and 1.16 (1.02 to 1.32) in secondary schoolchildren. Most of the increased risk was localized to within 90 m of the roadside. Among primary schoolchildren, effects were stronger in girls than boys (P-interaction = 0.02). Living within approximately 90 m of a main road is associated with a proximity-related increase in the risk of wheezing illness in children.	18	185	2001	4	10.1164/rccm2106126	General & Internal Medicine; Respiratory System
Organic compounds in indoor air - their relevance for perceived indoor air quality?. It is generally believed that indoor air pollution, one way or another may cause indoor air complaints. However, any association between volatile organic compounds (VOCs) concentrations and increase of indoor climate complaints, like the sick-building syndrome symptoms, is not straightforward. The reported symptom rates of, in particular, eye and upper airway irritation cannot generally be explained by our present knowledge of common chemically non-reactive VOCs measured indoors. Recently, experimental evidence has shown those chemical reactions between ozone (either with or without nitrogen dioxide) and unsaturated organic compounds (e.g. from citrus and pine oils) produce strong eye and airway irritating species. These have not yet been well characterised by conventional sampling and analytical techniques. The chemical reactions can occur indoors, and there is indirect evidence that they are associated with eye and airway irritation. However, many other volatile and non-volatile organic compounds have not generally been measured which could equally well have potent biological effects and cause an increase of complaint rates, and posses a health/comfort risk. As a consequence, it is recommended to use a broader analytical window of organic compounds than the classic VOC window as defined by the World Health Organisation. It may include hitherto not yet sampled or identified intermediary species (e.g., radicals, hydroperoxides and ionic compounds like detergents) as well as species deposited onto particles. Additionally, sampling strategies including emission testing of building products should carefully be linked to the measurement of organic compounds that are expected, based on the best available toxicological knowledge, to have biological effects at indoor concentrations. (C) 2001 Elsevier Science Ltd. All rights reserved.. airway irritation| indoor air quality| ocia| odour annoyance| tvoc| volatile organic compounds (vocs)|sick building syndrome| environmental tobacco-smoke| biological evaluation| material emissions| inhaled allergen| risk-assessment| office workers| eye irritation| voc emissions| ozone.	SEP-2001	airway irritation| indoor air quality| ocia| odour annoyance| tvoc| volatile organic compounds (vocs)|sick building syndrome| environmental tobacco-smoke| biological evaluation| material emissions| inhaled allergen| risk-assessment| office workers| eye irritation| voc emissions| ozone	Wolkoff, P; Nielsen, GD	Organic compounds in indoor air - their relevance for perceived indoor air quality?		ATMOSPHERIC ENVIRONMENT	airway irritation; indoor air quality; OCIA; odour annoyance; TVOC; volatile organic compounds (VOCs)	SICK BUILDING SYNDROME; ENVIRONMENTAL TOBACCO-SMOKE; BIOLOGICAL EVALUATION; MATERIAL EMISSIONS; INHALED ALLERGEN; RISK-ASSESSMENT; OFFICE WORKERS; EYE IRRITATION; VOC EMISSIONS; OZONE	It is generally believed that indoor air pollution, one way or another may cause indoor air complaints. However, any association between volatile organic compounds (VOCs) concentrations and increase of indoor climate complaints, like the sick-building syndrome symptoms, is not straightforward. The reported symptom rates of, in particular, eye and upper airway irritation cannot generally be explained by our present knowledge of common chemically non-reactive VOCs measured indoors. Recently, experimental evidence has shown those chemical reactions between ozone (either with or without nitrogen dioxide) and unsaturated organic compounds (e.g. from citrus and pine oils) produce strong eye and airway irritating species. These have not yet been well characterised by conventional sampling and analytical techniques. The chemical reactions can occur indoors, and there is indirect evidence that they are associated with eye and airway irritation. However, many other volatile and non-volatile organic compounds have not generally been measured which could equally well have potent biological effects and cause an increase of complaint rates, and posses a health/comfort risk. As a consequence, it is recommended to use a broader analytical window of organic compounds than the classic VOC window as defined by the World Health Organisation. It may include hitherto not yet sampled or identified intermediary species (e.g., radicals, hydroperoxides and ionic compounds like detergents) as well as species deposited onto particles. Additionally, sampling strategies including emission testing of building products should carefully be linked to the measurement of organic compounds that are expected, based on the best available toxicological knowledge, to have biological effects at indoor concentrations. (C) 2001 Elsevier Science Ltd. All rights reserved.	87	185	2001	11	10.1016/S1352-2310(01)00244-8	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Traffic-related air pollution is associated with atopy in children living in urban areas. Traffic emissions are a major source of air pollution in Western industrialized countries. To investigate the association between traffic-related air pollution and parameters of atopy, we studied 317 children 9 years of age living near major roads in two urban areas and one suburban area of a city in West Germany. Atopic sensitization was analyzed by skin-prick testing and determination of allergen-specific serum immunoglobulin E. Parents recorded allergic symptoms in a symptom diary, and physicians assessed allergic diseases. Personal NO2 exposure and NO2 concentrations in front of each child's home were measured. Outdoor NO2 was a good predictor for traffic exposure but a poor predictor for NO2 exposure at the personal level. Atopy was found to be related to outdoor NO2 (odds ratio for the association between symptoms of allergic rhinitis and outdoor NO2 = 1.81; 95% confidence interval = 1.02-3.21) but not to personal NO2 (odds ratio for the association between symptoms of allergic rhinitis and personal NO2 = 0.99; 95% confidence interval = 0.55-1.79). When the analysis was restricted to urban areas, we found that hay fever, symptoms of allergic rhinitis, wheezing, sensitization against pollen, house dust mites or cats, and milk or eggs were associated with outdoor NO2. The results indicate that traffic-related air pollution leads to increased prevalence of atopic sensitizations, allergic symptoms, and diseases.. air pollution| traffic| atopy| child| nitrogen dioxide| living conditions| urban environment| gender|chronic respiratory symptoms| nitrogen-dioxide exposure| diesel exhaust particles| automobile exhaust| asthmatic-patients| allergic rhinitis| inhaled allergen| lung-function| health| prevalence.	JAN-2000	air pollution| traffic| atopy| child| nitrogen dioxide| living conditions| urban environment| gender|chronic respiratory symptoms| nitrogen-dioxide exposure| diesel exhaust particles| automobile exhaust| asthmatic-patients| allergic rhinitis| inhaled allergen| lung-function| health| prevalence	Kramer, U; Koch, T; Ranft, U; Ring, J; Behrendt, H	Traffic-related air pollution is associated with atopy in children living in urban areas		EPIDEMIOLOGY	air pollution; traffic; atopy; child; nitrogen dioxide; living conditions; urban environment; gender	CHRONIC RESPIRATORY SYMPTOMS; NITROGEN-DIOXIDE EXPOSURE; DIESEL EXHAUST PARTICLES; AUTOMOBILE EXHAUST; ASTHMATIC-PATIENTS; ALLERGIC RHINITIS; INHALED ALLERGEN; LUNG-FUNCTION; HEALTH; PREVALENCE	Traffic emissions are a major source of air pollution in Western industrialized countries. To investigate the association between traffic-related air pollution and parameters of atopy, we studied 317 children 9 years of age living near major roads in two urban areas and one suburban area of a city in West Germany. Atopic sensitization was analyzed by skin-prick testing and determination of allergen-specific serum immunoglobulin E. Parents recorded allergic symptoms in a symptom diary, and physicians assessed allergic diseases. Personal NO2 exposure and NO2 concentrations in front of each child's home were measured. Outdoor NO2 was a good predictor for traffic exposure but a poor predictor for NO2 exposure at the personal level. Atopy was found to be related to outdoor NO2 (odds ratio for the association between symptoms of allergic rhinitis and outdoor NO2 = 1.81; 95% confidence interval = 1.02-3.21) but not to personal NO2 (odds ratio for the association between symptoms of allergic rhinitis and personal NO2 = 0.99; 95% confidence interval = 0.55-1.79). When the analysis was restricted to urban areas, we found that hay fever, symptoms of allergic rhinitis, wheezing, sensitization against pollen, house dust mites or cats, and milk or eggs were associated with outdoor NO2. The results indicate that traffic-related air pollution leads to increased prevalence of atopic sensitizations, allergic symptoms, and diseases.	35	185	2000	7	10.1097/00001648-200001000-00014	Public, Environmental & Occupational Health
Effect of Early Life Exposure to Air Pollution on Development of Childhood Asthma. BACKGROUND: There is increasing recognition of the importance of early environmental exposures in the development of childhood asthma. Outdoor air pollution is a recognized asthma trigger, but it is unclear whether exposure influences incident disease. We investigated the effect of exposure to ambient air pollution in utero and during the first year of life oil risk of subsequent asthma diagnosis in a population-based nested case-control study. METHODS: We assessed all children born in southwestern British Columbia in 1999 and 2000 (n = 37,401) for incidence of asthma diagnosis tip to 3-4 years of age using outpatient and hospitalization records. Asthma cases were age- and sex-matched to five randomly chosen controls from the eligible cohort. We estimated each individual's exposure to ambient air pollution for the gestational period and first year of life using high-resolution pollution surfaces derived from regulatory monitoring data as well as land use regression models adjusted for temporal variation. We used logistic regression analyses to estimate effects of carbon monoxide, nitric oxide, nitrogen dioxide, particulate matter <= 10 mu m and < 2.5 mu m in aerodynamic diameter (PM(10) and PM(2.5)), ozone, sulfur dioxide, black carbon, woodsmoke, and proximity to roads and point sources on asthma diagnosis. RESULTS: A total of 3,482 children (9%) were classified as asthma cases. We observed a statistically significantly increased risk of asthma diagnosis with increased earl), life exposure to CO, NO, NO(2), PM(10), SO(2), and black carbon and proximity to point sources. Traffic-related pollutants were associated with the highest risks: adjusted odds ratio = 1.08 (95% confidence interval, 1.04-1.12) for a 10-mu g/m(3) increase of NO, 1.12 (1.07-1.17) for a 10-mu g/m(3) increase in NO(2), and 1.10 (1.06-1.13) for a 100-mu g/m(3) increase in CO. These data support the hypothesis that early childhood exposure to air pollutants plays a role in development of asthma.. administrative data| air pollution| asthma| children's health| in utero| respiratory| traffic|land-use regression| respiratory health| southern california| birth cohort| particulate matter| pulmonary-function| children| symptoms| woodsmoke| outcomes.	FEB-2010	administrative data| air pollution| asthma| children's health| in utero| respiratory| traffic|land-use regression| respiratory health| southern california| birth cohort| particulate matter| pulmonary-function| children| symptoms| woodsmoke| outcomes	Clark, NA; Demers, PA; Karr, CJ; Koehoorn, M; Lencar, C; Tamburic, L; Brauer, M	Effect of Early Life Exposure to Air Pollution on Development of Childhood Asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	administrative data; air pollution; asthma; children's health; in utero; respiratory; traffic	LAND-USE REGRESSION; RESPIRATORY HEALTH; SOUTHERN CALIFORNIA; BIRTH COHORT; PARTICULATE MATTER; PULMONARY-FUNCTION; CHILDREN; SYMPTOMS; WOODSMOKE; OUTCOMES	BACKGROUND: There is increasing recognition of the importance of early environmental exposures in the development of childhood asthma. Outdoor air pollution is a recognized asthma trigger, but it is unclear whether exposure influences incident disease. We investigated the effect of exposure to ambient air pollution in utero and during the first year of life oil risk of subsequent asthma diagnosis in a population-based nested case-control study. METHODS: We assessed all children born in southwestern British Columbia in 1999 and 2000 (n = 37,401) for incidence of asthma diagnosis tip to 3-4 years of age using outpatient and hospitalization records. Asthma cases were age- and sex-matched to five randomly chosen controls from the eligible cohort. We estimated each individual's exposure to ambient air pollution for the gestational period and first year of life using high-resolution pollution surfaces derived from regulatory monitoring data as well as land use regression models adjusted for temporal variation. We used logistic regression analyses to estimate effects of carbon monoxide, nitric oxide, nitrogen dioxide, particulate matter <= 10 mu m and < 2.5 mu m in aerodynamic diameter (PM(10) and PM(2.5)), ozone, sulfur dioxide, black carbon, woodsmoke, and proximity to roads and point sources on asthma diagnosis. RESULTS: A total of 3,482 children (9%) were classified as asthma cases. We observed a statistically significantly increased risk of asthma diagnosis with increased earl), life exposure to CO, NO, NO(2), PM(10), SO(2), and black carbon and proximity to point sources. Traffic-related pollutants were associated with the highest risks: adjusted odds ratio = 1.08 (95% confidence interval, 1.04-1.12) for a 10-mu g/m(3) increase of NO, 1.12 (1.07-1.17) for a 10-mu g/m(3) increase in NO(2), and 1.10 (1.06-1.13) for a 100-mu g/m(3) increase in CO. These data support the hypothesis that early childhood exposure to air pollutants plays a role in development of asthma.	52	184	2010	7	10.1289/ehp.0900916	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Hypersensitivity reactions to chemotherapy: Outcomes and safety of rapid desensitization in 413 cases. Background: Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent. Objective: We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol. Methods: Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records. Results: Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective. Conclusions: Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs.. anaphylaxis| chemotherapy agents| monoclonal antibodies| rapid desensitization| hypersensitivity reactions| carboplatin| paclitaxel| adverse drug reactions|carboplatin hypersensitivity| ovarian-cancer| protocol| paclitaxel| skin| cisplatin| allergy| taxol| experience.	SEP-2008	anaphylaxis| chemotherapy agents| monoclonal antibodies| rapid desensitization| hypersensitivity reactions| carboplatin| paclitaxel| adverse drug reactions|carboplatin hypersensitivity| ovarian-cancer| protocol| paclitaxel| skin| cisplatin| allergy| taxol| experience	Castells, MC; Tennant, NM; Sloane, DE; Hsu, FI; Barrett, NA; Hong, DI; Laidlaw, TM; Legere, HJ; Nallamshetty, SN; Palis, RI; Rao, JJ; Berlin, ST; Campos, SM; Matulonis, UA	Hypersensitivity reactions to chemotherapy: Outcomes and safety of rapid desensitization in 413 cases		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	anaphylaxis; chemotherapy agents; monoclonal antibodies; rapid desensitization; hypersensitivity reactions; carboplatin; paclitaxel; adverse drug reactions	CARBOPLATIN HYPERSENSITIVITY; OVARIAN-CANCER; PROTOCOL; PACLITAXEL; SKIN; CISPLATIN; ALLERGY; TAXOL; EXPERIENCE	Background: Hypersensitivity reactions (HSRs) to chemotherapeutic drugs, including mAbs, often require that the provoking medication be discontinued, thus raising a dilemma for the caregiver: further use could precipitate a severe, even fatal, allergic reaction on re-exposure, but alternative drugs might be poorly tolerated or much less effective compared with the preferred agent. Objective: We have developed a standardized rapid desensitization protocol for achieving temporary tolerization to drug allergens. In this study we evaluate the safety and efficacy of this protocol. Methods: Ninety-eight patients who had HSRs in response to treatment with carboplatin, cisplatin, oxaliplatin, paclitaxel, liposomal doxorubicin, doxorubicin, or rituximab received rapid desensitization to these agents. A standardized 12-step protocol was used, with treatment given intravenously or intraperitoneally. Initial desensitizations occurred in the medical intensive care unit, whereas most subsequent infusions took place in an outpatient setting. Safety and efficacy of the protocol were assessed by review of treatment records. Results: Of the 413 desensitizations performed, 94% induced mild or no reactions. No life-threatening HSRs or deaths occurred during the procedure, and all patients received their full target dose. Most reactions occurred during the first desensitization. Reactions were most commonly reported at the last step of the protocol. Desensitizations through the intravenous and intraperitoneal routes were equally effective. Conclusions: Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care at our institutions in treating patients with HSRs to chemotherapeutic drugs, including mAbs.	24	184	2008	7	10.1016/j.jaci.2008.02.044	Allergy; Immunology
Association of domestic exposure to volatile organic compounds with asthma in young children. Aim: To investigate the association between domestic exposure to volatile organic compounds (VOCs) and asthma in young children. Methods: A population based case-control study was conducted in Perth, Western Australia in children aged between 6 months and 3 years. Cases ( n = 88) were children recruited at Princess Margaret Hospital accident and emergency department and discharged with asthma as the primary diagnosis; 104 controls consisted of children from the same age group without an asthma diagnosis identified through the Health Department of Western Australia. Information regarding the health status of the study children and characteristics of the home was collected using a standardised questionnaire. Exposure to VOCs, average temperature and relative humidity were measured in winter and summer in the living room of each participating household. Results: Cases were exposed to significantly higher VOC levels (mug/m(3)) than controls (p< 0.01). Most of the individual VOCs appeared to be significant risk factors for asthma with the highest odds ratios for benzene followed by ethylbenzene and toluene. For every 10 unit increase in the concentration of toluene and benzene (mu g/m(3)) the risk of having asthma increased by almost two and three times, respectively. Conclusions: Domestic exposure to VOCs at levels below currently accepted recommendations may increase the risk of childhood asthma. Measurement of total VOCs may underestimate the risks associated with individual compounds.. childhood asthma| indoor air| prevalence| formaldehyde| population| allergy| health.	SEP-2004	childhood asthma| indoor air| prevalence| formaldehyde| population| allergy| health	Rumchev, K; Spickett, J; Bulsara, M; Phillips, M; Stick, S	Association of domestic exposure to volatile organic compounds with asthma in young children		THORAX		CHILDHOOD ASTHMA; INDOOR AIR; PREVALENCE; FORMALDEHYDE; POPULATION; ALLERGY; HEALTH	Aim: To investigate the association between domestic exposure to volatile organic compounds (VOCs) and asthma in young children. Methods: A population based case-control study was conducted in Perth, Western Australia in children aged between 6 months and 3 years. Cases ( n = 88) were children recruited at Princess Margaret Hospital accident and emergency department and discharged with asthma as the primary diagnosis; 104 controls consisted of children from the same age group without an asthma diagnosis identified through the Health Department of Western Australia. Information regarding the health status of the study children and characteristics of the home was collected using a standardised questionnaire. Exposure to VOCs, average temperature and relative humidity were measured in winter and summer in the living room of each participating household. Results: Cases were exposed to significantly higher VOC levels (mug/m(3)) than controls (p< 0.01). Most of the individual VOCs appeared to be significant risk factors for asthma with the highest odds ratios for benzene followed by ethylbenzene and toluene. For every 10 unit increase in the concentration of toluene and benzene (mu g/m(3)) the risk of having asthma increased by almost two and three times, respectively. Conclusions: Domestic exposure to VOCs at levels below currently accepted recommendations may increase the risk of childhood asthma. Measurement of total VOCs may underestimate the risks associated with individual compounds.	27	184	2004	6	10.1136/thx.2003.013680	Respiratory System
A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease. The respiratory allergens that induce experimental. Th cell type 2-dependent allergic lung inflammation may be grouped into two functional classes. One class of allergens, in this study termed type I, requires priming with adjuvants remote from the lung to overcome airway tolerogenic mechanisms that ordinarily preclude allergic responses to inhaled Ags. In contrast, the other, or type II, allergen class requires neither remote priming nor additional adjuvants to overcome airway tolerance and elicit robust allergic lung disease. In this study, we show in an experimental model that diverse type II allergens share in common proteolytic activity that is both necessary and sufficient for overcoming airway tolerance and induction of pulmonary allergic disease. Inactivated protease and protease-free Ag fragments showed no allergenic potency, demonstrating that only active protease acting on endogenous substrates was essential. Furthermore, induction of airway tolerance could be aborted and allergic lung disease established by simply adding purified protease to a type I allergen. Thus, exogenous proteases are common to type II allergens and may be generally required to overcome the innate resistance of the airway to Th cell type 2 activation and allergic inflammation, raising concern for their potential contribution to diseases such as asthma.. dust-mite allergen| induced airway hyperreactivity| murine model| ifn-gamma| proteolytic activity| cysteine protease| guinea-pig| physicochemical characterization| aspergillus-fumigatus| detergent enzymes.	NOV 15-2002	dust-mite allergen| induced airway hyperreactivity| murine model| ifn-gamma| proteolytic activity| cysteine protease| guinea-pig| physicochemical characterization| aspergillus-fumigatus| detergent enzymes	Kheradmand, F; Kiss, A; Xu, J; Lee, SH; Kolattukudy, PE; Corry, DB	A protease-activated pathway underlying Th cell type 2 activation and allergic lung disease		JOURNAL OF IMMUNOLOGY		DUST-MITE ALLERGEN; INDUCED AIRWAY HYPERREACTIVITY; MURINE MODEL; IFN-GAMMA; PROTEOLYTIC ACTIVITY; CYSTEINE PROTEASE; GUINEA-PIG; PHYSICOCHEMICAL CHARACTERIZATION; ASPERGILLUS-FUMIGATUS; DETERGENT ENZYMES	The respiratory allergens that induce experimental. Th cell type 2-dependent allergic lung inflammation may be grouped into two functional classes. One class of allergens, in this study termed type I, requires priming with adjuvants remote from the lung to overcome airway tolerogenic mechanisms that ordinarily preclude allergic responses to inhaled Ags. In contrast, the other, or type II, allergen class requires neither remote priming nor additional adjuvants to overcome airway tolerance and elicit robust allergic lung disease. In this study, we show in an experimental model that diverse type II allergens share in common proteolytic activity that is both necessary and sufficient for overcoming airway tolerance and induction of pulmonary allergic disease. Inactivated protease and protease-free Ag fragments showed no allergenic potency, demonstrating that only active protease acting on endogenous substrates was essential. Furthermore, induction of airway tolerance could be aborted and allergic lung disease established by simply adding purified protease to a type I allergen. Thus, exogenous proteases are common to type II allergens and may be generally required to overcome the innate resistance of the airway to Th cell type 2 activation and allergic inflammation, raising concern for their potential contribution to diseases such as asthma.	76	184	2002	8		Immunology
"Eosinophils generate brominating oxidants in allergen-induced asthma. Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific ""molecular fingerprint"" for proteins modified through the eosinophil peroxidase-H2O2 system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase, Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans.. human neutrophils employ| hydrogen-peroxide| amino-acids| schistosoma-mansoni| reactive aldehydes| molecular-cloning| antigen challenge| singlet oxygen| guinea-pig| myeloperoxidase."	MAY-2000	human neutrophils employ| hydrogen-peroxide| amino-acids| schistosoma-mansoni| reactive aldehydes| molecular-cloning| antigen challenge| singlet oxygen| guinea-pig| myeloperoxidase	Wu, WJ; Samoszuk, MK; Comhair, SAA; Thomassen, MJ; Farver, CF; Dweik, RA; Kavuru, MS; Erzurum, SC; Hazen, SL	Eosinophils generate brominating oxidants in allergen-induced asthma		JOURNAL OF CLINICAL INVESTIGATION		HUMAN NEUTROPHILS EMPLOY; HYDROGEN-PEROXIDE; AMINO-ACIDS; SCHISTOSOMA-MANSONI; REACTIVE ALDEHYDES; MOLECULAR-CLONING; ANTIGEN CHALLENGE; SINGLET OXYGEN; GUINEA-PIG; MYELOPEROXIDASE	"Eosinophils promote tissue injury and contribute to the pathogenesis of allergen-triggered diseases like asthma, but the chemical basis of damage to eosinophil targets is unknown. We now demonstrate that eosinophil activation in vivo results in oxidative damage of proteins through bromination of tyrosine residues, a heretofore unrecognized pathway for covalent modification of biologic targets in human tissues. Mass spectrometric studies demonstrated that 3-bromotyrosine serves as a specific ""molecular fingerprint"" for proteins modified through the eosinophil peroxidase-H2O2 system in the presence of plasma levels of halides. We applied a localized allergen challenge to model the effects of eosinophils and brominating oxidants in human lung injury. Endobronchial biopsy specimens from allergen-challenged lung segments of asthmatic, but not healthy control, subjects demonstrated significant enrichments in eosinophils and eosinophil peroxidase, Baseline levels of 3-bromotyrosine in bronchoalveolar lavage (BAL) proteins from mildly allergic asthmatic individuals were modestly but not statistically significantly elevated over those in control subjects. After exposure to segmental allergen challenge, lung segments of asthmatics, but not healthy control subjects, exhibited a >10-fold increase in BAL 3-bromotyrosine content, but only two- to threefold increases in 3-chlorotyrosine, a specific oxidation product formed by neutrophil- and monocyte-derived myeloperoxidase. These results identify reactive brominating species produced by eosinophils as a distinct class of oxidants formed in vivo. They also reveal eosinophil peroxidase as a potential therapeutic target for allergen-triggered inflammatory tissue injury in humans."	67	184	2000	9	10.1172/JCI9702	Research & Experimental Medicine
Airway nitric oxide diffusion in asthma - Role in pulmonary function and bronchial responsiveness. If the nitric oxide (NO) diffusing capacity of the airways (DNO) is the quantity of NO diffusing per unit time into exhaled gas ((q) over dot) divided by the difference between the concentration of NO in the airway wall (C-w) and lumen, then DNO and C-w can be estimated from the relationship between exhaled NO concentration and expiratory flow, in 10 normal subjects and 25 asthmatic patients before and after treatment with inhaled beclomethasone, DNO averaged 6.8 +/- 1.2, 25.5 +/- 3.8, and 22.3 +/- 2.7 nl/s/ppb x 10(-3) respectively; C-w averaged 149 +/- 31.9, 255.3 +/- 46.4 and 108.3 +/- 14.3 ppb, respectively; and DNOCw (the maximal q from diffusion) averaged 1,020 +/- 157.5, 6,512 +/- 866, and 2416 +/- 208.5 nl/s x 10-3, respectively. DNO and DNOCw in the asthmatic subjects before and after steroids were greater than in normal subjects (p < 0.0001), but C-w was not different. Within asthmatic subjects, steroids caused C-w and DNOCw to fall (p < 0.0001), but DNO was Unchanged, DNOCw after steroids, presumably reflecting maximal diffusion of constitutive NO, was positively correlated with methacholine PC20 and FEV1/FVC before or after steroids. The increased DNO measured in asthmatic patients may reflect upregulation of nonadrenergic, noncholinergic, NO-producing nerves in airways in compensation for decreased sensitivity of airway smooth muscle to the relaxant effects of endogenous NO.. exhaled air| mild asthma| synthase| hyperreactivity| inhibition| induction| humans| liver| lung.	APR-2000	exhaled air| mild asthma| synthase| hyperreactivity| inhibition| induction| humans| liver| lung	Silkoff, PE; Sylvester, JT; Zamel, N; Permutt, S	Airway nitric oxide diffusion in asthma - Role in pulmonary function and bronchial responsiveness		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		EXHALED AIR; MILD ASTHMA; SYNTHASE; HYPERREACTIVITY; INHIBITION; INDUCTION; HUMANS; LIVER; LUNG	If the nitric oxide (NO) diffusing capacity of the airways (DNO) is the quantity of NO diffusing per unit time into exhaled gas ((q) over dot) divided by the difference between the concentration of NO in the airway wall (C-w) and lumen, then DNO and C-w can be estimated from the relationship between exhaled NO concentration and expiratory flow, in 10 normal subjects and 25 asthmatic patients before and after treatment with inhaled beclomethasone, DNO averaged 6.8 +/- 1.2, 25.5 +/- 3.8, and 22.3 +/- 2.7 nl/s/ppb x 10(-3) respectively; C-w averaged 149 +/- 31.9, 255.3 +/- 46.4 and 108.3 +/- 14.3 ppb, respectively; and DNOCw (the maximal q from diffusion) averaged 1,020 +/- 157.5, 6,512 +/- 866, and 2416 +/- 208.5 nl/s x 10-3, respectively. DNO and DNOCw in the asthmatic subjects before and after steroids were greater than in normal subjects (p < 0.0001), but C-w was not different. Within asthmatic subjects, steroids caused C-w and DNOCw to fall (p < 0.0001), but DNO was Unchanged, DNOCw after steroids, presumably reflecting maximal diffusion of constitutive NO, was positively correlated with methacholine PC20 and FEV1/FVC before or after steroids. The increased DNO measured in asthmatic patients may reflect upregulation of nonadrenergic, noncholinergic, NO-producing nerves in airways in compensation for decreased sensitivity of airway smooth muscle to the relaxant effects of endogenous NO.	31	184	2000	11		General & Internal Medicine; Respiratory System
A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma. Asthma is an inflammatory disorder caused by airway exposures to allergens and chemical irritants. Studies focusing on immune, smooth muscle, and airway epithelial function revealed many aspects of the disease mechanism of asthma. However, the limited efficacies of immune-directed therapies suggest the involvement of additional mechanisms in asthmatic airway inflammation. TRPA1 is an irritant-sensing ion channel expressed in airway chemosensory nerves. TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma. Here, we examined the role of TRPA1 in allergic asthma in the murine ovalbumin model. Strikingly, genetic ablation of TRPA1 inhibited allergen-induced leukocyte infiltration in the airways, reduced cytokine and mucus production, and almost completely abolished airway hyperreactivity to contractile stimuli. This phenotype is recapitulated by treatment of wild-type mice with HC-030031, a TRPA1 antagonist. HC-030031, when administered during airway allergen challenge, inhibited eosinophil infiltration and prevented the development of airway hyperreactivity. Trpa1(-/-) mice displayed deficiencies in chemically and allergen-induced neuropeptide release in the airways, providing a potential explanation for the impaired inflammatory response. Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge. TRPA1 may represent a promising pharmacological target for the treatment of asthma and other allergic inflammatory conditions.. airway hyperreactivity| trp channel| trpa1|neurogenic inflammation| trpa1| pain| receptor| nociception| activation| mechanisms| sensation| diseases| fibers.	JUN 2-2009	airway hyperreactivity| trp channel| trpa1|neurogenic inflammation| trpa1| pain| receptor| nociception| activation| mechanisms| sensation| diseases| fibers	Caceres, AI; Brackmann, M; Elia, MD; Bessac, BF; del Camino, D; D'Amours, M; Witek, JS; Fanger, CM; Chong, JA; Hayward, NJ; Homer, RJ; Cohn, L; Huang, XZ; Moran, MM; Jordt, SE	A sensory neuronal ion channel essential for airway inflammation and hyperreactivity in asthma		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	airway hyperreactivity; TRP channel; TRPA1	NEUROGENIC INFLAMMATION; TRPA1; PAIN; RECEPTOR; NOCICEPTION; ACTIVATION; MECHANISMS; SENSATION; DISEASES; FIBERS	Asthma is an inflammatory disorder caused by airway exposures to allergens and chemical irritants. Studies focusing on immune, smooth muscle, and airway epithelial function revealed many aspects of the disease mechanism of asthma. However, the limited efficacies of immune-directed therapies suggest the involvement of additional mechanisms in asthmatic airway inflammation. TRPA1 is an irritant-sensing ion channel expressed in airway chemosensory nerves. TRPA1-activating stimuli such as cigarette smoke, chlorine, aldehydes, and scents are among the most prevalent triggers of asthma. Endogenous TRPA1 agonists, including reactive oxygen species and lipid peroxidation products, are potent drivers of allergen-induced airway inflammation in asthma. Here, we examined the role of TRPA1 in allergic asthma in the murine ovalbumin model. Strikingly, genetic ablation of TRPA1 inhibited allergen-induced leukocyte infiltration in the airways, reduced cytokine and mucus production, and almost completely abolished airway hyperreactivity to contractile stimuli. This phenotype is recapitulated by treatment of wild-type mice with HC-030031, a TRPA1 antagonist. HC-030031, when administered during airway allergen challenge, inhibited eosinophil infiltration and prevented the development of airway hyperreactivity. Trpa1(-/-) mice displayed deficiencies in chemically and allergen-induced neuropeptide release in the airways, providing a potential explanation for the impaired inflammatory response. Our data suggest that TRPA1 is a key integrator of interactions between the immune and nervous systems in the airways, driving asthmatic airway inflammation following inhaled allergen challenge. TRPA1 may represent a promising pharmacological target for the treatment of asthma and other allergic inflammatory conditions.	32	183	2009	6	10.1073/pnas.0900591106	Science & Technology - Other Topics
Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL consensus report. There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.. atopic dermatitis| children| adults| risk factors| immunopathology| diagnosis| systemic treatment| topical treatment|randomized controlled-trial| staphylococcus-aureus colonization| topical calcineurin inhibitors| pimecrolimus cream 1-percent| plasmacytoid dendritic cells| placebo-controlled trial| dust-mite allergens| regulatory t-cells| long-term efficacy| double-blind.	AUG-2006	atopic dermatitis| children| adults| risk factors| immunopathology| diagnosis| systemic treatment| topical treatment|randomized controlled-trial| staphylococcus-aureus colonization| topical calcineurin inhibitors| pimecrolimus cream 1-percent| plasmacytoid dendritic cells| placebo-controlled trial| dust-mite allergens| regulatory t-cells| long-term efficacy| double-blind	Akdis, CA; Akdis, M; Bieber, T; Bindslev-Jensen, C; Boguniewicz, M; Eigenmann, P; Hamid, Q; Kapp, A; Leung, DYM; Lipozencic, J; Luger, TA; Muraro, A; Novak, N; Platts-Mills, TAE; Rosenwasser, L; Scheynius, A; Simons, FER; Spergel, J; Turjanmaa, K; Wahn, U; Weidinger, S; Werfel, T; Zuberbier, T	Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL consensus report		ALLERGY	atopic dermatitis; children; adults; risk factors; immunopathology; diagnosis; systemic treatment; topical treatment	RANDOMIZED CONTROLLED-TRIAL; STAPHYLOCOCCUS-AUREUS COLONIZATION; TOPICAL CALCINEURIN INHIBITORS; PIMECROLIMUS CREAM 1-PERCENT; PLASMACYTOID DENDRITIC CELLS; PLACEBO-CONTROLLED TRIAL; DUST-MITE ALLERGENS; REGULATORY T-CELLS; LONG-TERM EFFICACY; DOUBLE-BLIND	There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.	200	183	2006	19	10.1111/j.1398-9995.2006.01153.x	Allergy; Immunology
The 'microflora hypothesis' of allergic diseases. Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in 'industrialized' countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this 'microflora hypothesis' includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a 'balanced' microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy.. chain fatty-acids| placebo-controlled trial| anthroposophic life-style| oral tolerance induction| regulatory t-cells| intestinal microflora| dendritic cells| candida-albicans| early-childhood| atopic disease.	DEC-2005	chain fatty-acids| placebo-controlled trial| anthroposophic life-style| oral tolerance induction| regulatory t-cells| intestinal microflora| dendritic cells| candida-albicans| early-childhood| atopic disease	Noverr, MC; Huffnagle, GB	The 'microflora hypothesis' of allergic diseases		CLINICAL AND EXPERIMENTAL ALLERGY		CHAIN FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; ANTHROPOSOPHIC LIFE-STYLE; ORAL TOLERANCE INDUCTION; REGULATORY T-CELLS; INTESTINAL MICROFLORA; DENDRITIC CELLS; CANDIDA-ALBICANS; EARLY-CHILDHOOD; ATOPIC DISEASE	Increasingly, epidemiologic and clinical data support the hypothesis that perturbations in the gastrointestinal (GI) microbiota because of antibiotic use and dietary differences in 'industrialized' countries have disrupted the normal microbiota-mediated mechanisms of immunological tolerance in the mucosa, leading to an increase in the incidence of allergic airway disease. The data supporting this 'microflora hypothesis' includes correlations between allergic airway disease and (1) antibiotic use early in life, (2) altered fecal microbiota and (3) dietary changes over the past two decades. Our laboratory has recently demonstrated that mice can develop allergic airway responses to allergens if their endogenous microbiota is altered at the time of first allergen exposure. These experimental and clinical observations are consistent with other studies demonstrating that the endogenous microbiota plays a significant role in shaping the development of the immune system. Data are beginning to accumulate that a 'balanced' microbiota plays a positive role in maintaining mucosal immunologic tolerance long after post-natal development. Other studies have demonstrated that even small volumes delivered to the nasopharynx largely end up in the GI tract, suggesting that airway tolerance and oral tolerance may operate simultaneously. The mechanism of microbiota modulation of host immunity is not known; however, host and microbial oxylipins are one potential set of immunomodulatory molecules that may control mucosal tolerance. The cumulative data are beginning to support the notion that probiotic and prebiotic strategies be considered for patients coming off of antibiotic therapy.	119	183	2005	10	10.1111/j.1365-2222.2005.02379.x	Allergy; Immunology
Posttraumatic stress disorder in female veterans - Association with self-reported health problems and functional impairment. Background: The purpose of this report is to identify self-reported health problems and functional impairment associated with screening positive for posttraumatic stress disorder (PTSD) in women seen for care at a Department of Veterans Affairs (VA) medical center. Methods: A survey was mailed to all women (N = 1935) who received care at the VA Puget Sound Health Care System between October 1996 and January 1998. The survey inquired about health history and habits. It included the PTSD Checklist-Civilian Version (PCL-C) and validated screening measures for other psychiatric disorders. The veteran's version of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36-V) was included to assess health-related quality of life. Results: Of the 1259 eligible women who completed the survey, 266 women (21%) screened positive for current PTSD (PCL-C score greater than or equal to50). In age-adjusted bivariate analyses, women who screened positive for PTSD reported more psychiatric problems, substance abuse, and lifetime exposure to domestic violence. They were significantly more likely to endorse physical health problems including obesity, smoking, irritable bowel syndrome, fibromyalgia, chronic pelvic pain, polycystic ovary disease, asthma, cervical cancer, and stroke. In fully adjusted multivariate models, a PCL-C score of 50 or greater was independently associated with scoring in the lowest quartile on SF-36-V subscales and composite scales. Conclusions: Symptoms of PTSD are common in women treated at VA facilities. In addition, PTSD is associated with self-reported mental and physical health problems and poor health-related quality of life in these patients. These findings have implications for the design of VA primary care services for the growing population of female veterans.. quality-of-life| male vietnam veterans| ptsd checklist| primary-care| screening instrument| sexual victimization| traumatic events| affairs patients| breast-cancer| desert-storm.	FEB 23-2004	quality-of-life| male vietnam veterans| ptsd checklist| primary-care| screening instrument| sexual victimization| traumatic events| affairs patients| breast-cancer| desert-storm	Dobie, DJ; Kivlahan, DR; Maynard, C; Bush, KR; Davis, TM; Bradley, KA	Posttraumatic stress disorder in female veterans - Association with self-reported health problems and functional impairment		ARCHIVES OF INTERNAL MEDICINE		QUALITY-OF-LIFE; MALE VIETNAM VETERANS; PTSD CHECKLIST; PRIMARY-CARE; SCREENING INSTRUMENT; SEXUAL VICTIMIZATION; TRAUMATIC EVENTS; AFFAIRS PATIENTS; BREAST-CANCER; DESERT-STORM	Background: The purpose of this report is to identify self-reported health problems and functional impairment associated with screening positive for posttraumatic stress disorder (PTSD) in women seen for care at a Department of Veterans Affairs (VA) medical center. Methods: A survey was mailed to all women (N = 1935) who received care at the VA Puget Sound Health Care System between October 1996 and January 1998. The survey inquired about health history and habits. It included the PTSD Checklist-Civilian Version (PCL-C) and validated screening measures for other psychiatric disorders. The veteran's version of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36-V) was included to assess health-related quality of life. Results: Of the 1259 eligible women who completed the survey, 266 women (21%) screened positive for current PTSD (PCL-C score greater than or equal to50). In age-adjusted bivariate analyses, women who screened positive for PTSD reported more psychiatric problems, substance abuse, and lifetime exposure to domestic violence. They were significantly more likely to endorse physical health problems including obesity, smoking, irritable bowel syndrome, fibromyalgia, chronic pelvic pain, polycystic ovary disease, asthma, cervical cancer, and stroke. In fully adjusted multivariate models, a PCL-C score of 50 or greater was independently associated with scoring in the lowest quartile on SF-36-V subscales and composite scales. Conclusions: Symptoms of PTSD are common in women treated at VA facilities. In addition, PTSD is associated with self-reported mental and physical health problems and poor health-related quality of life in these patients. These findings have implications for the design of VA primary care services for the growing population of female veterans.	60	183	2004	7	10.1001/archinte.164.4.394	General & Internal Medicine
Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: Assessment of response to methacholine and exercise challenge. Background: Imaging of gas distribution in the lungs of patients with asthma has been restricted because of the lack of a suitable gaseous contrast agent. Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance imaging of lung diseases. Objective: We sought to investigate the use of HHe3 gas to image the lungs of patients with moderate or severe asthma and to assess changes in gas distribution after methacholine and exercise challenge. Methods: Magnetic resonance imaging was performed in asthmatic patients immediately after inhalation of HHe3 gas. In addition, images were obtained before and after methacholine challenge and a standard exercise test. Results: Areas of the lung with no signal or sharply reduced HHe3 signal (ventilation defects) are common in patients with asthma, and the number of defects was inversely related to the percent predicted FEV1 (r = 0.71, P < .002). After methacholine challenge (n = 3), the number of defects increased. Similarly, imaging of the lungs after exercise (n = 6) showed increased ventilation defects in parallel with decreases in FEV1. The increase in defects after challenge in these 9 asthmatic patients was significant both for the number (P < .02) and extent (P < .02) of the defects. The variability and speed of changes in ventilation and the complete lack of signal in many areas is in keeping with a model in which the defects result from airway closure. Conclusion: HHe3 magnetic resonance provides a new technique for imaging the distribution of inhaled air in the lungs. The technique is suitable for following responses to treatment of asthma and changes after methacholine or exercise challenge.. asthma| helium| magnetic resonance imaging| imaging| ventilation| lungs|computed-tomography| he-3 gas| disease| airways| health.	JUN-2003	asthma| helium| magnetic resonance imaging| imaging| ventilation| lungs|computed-tomography| he-3 gas| disease| airways| health	Samee, S; Altes, T; Powers, P; de Lange, EE; Knight-Scott, J; Rakes, G; Mugler, JP; Ciambotti, JM; Alford, BA; Brookeman, JR; Platts-Mills, TAE	Imaging the lungs in asthmatic patients by using hyperpolarized helium-3 magnetic resonance: Assessment of response to methacholine and exercise challenge		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; helium; magnetic resonance imaging; imaging; ventilation; lungs	COMPUTED-TOMOGRAPHY; HE-3 GAS; DISEASE; AIRWAYS; HEALTH	Background: Imaging of gas distribution in the lungs of patients with asthma has been restricted because of the lack of a suitable gaseous contrast agent. Hyperpolarized helium-3 (HHe3) provides a new technique for magnetic resonance imaging of lung diseases. Objective: We sought to investigate the use of HHe3 gas to image the lungs of patients with moderate or severe asthma and to assess changes in gas distribution after methacholine and exercise challenge. Methods: Magnetic resonance imaging was performed in asthmatic patients immediately after inhalation of HHe3 gas. In addition, images were obtained before and after methacholine challenge and a standard exercise test. Results: Areas of the lung with no signal or sharply reduced HHe3 signal (ventilation defects) are common in patients with asthma, and the number of defects was inversely related to the percent predicted FEV1 (r = 0.71, P < .002). After methacholine challenge (n = 3), the number of defects increased. Similarly, imaging of the lungs after exercise (n = 6) showed increased ventilation defects in parallel with decreases in FEV1. The increase in defects after challenge in these 9 asthmatic patients was significant both for the number (P < .02) and extent (P < .02) of the defects. The variability and speed of changes in ventilation and the complete lack of signal in many areas is in keeping with a model in which the defects result from airway closure. Conclusion: HHe3 magnetic resonance provides a new technique for imaging the distribution of inhaled air in the lungs. The technique is suitable for following responses to treatment of asthma and changes after methacholine or exercise challenge.	19	183	2003	7	10.1067/mai.2003.1544	Allergy; Immunology
Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy. Background: Influence of household pets in the development of childhood asthma or atopy has been controversial. Objective: The purpose of this study was to investigate whether pet exposure in early life decreases the subsequent risk of frequent wheezing and/or allergic sensitization. Methods: This was a prospective observational birth cohort study. The setting was a large health maintenance organization in Tucson, Ariz; the subjects were a population sample of 1246 newborns enrolled at birth and followed prospectively to age 13 years. The main outcome measures were as follows: time to first report of frequent wheezing (>3 episodes in the past year), skin prick test reactivity at 6 years and 11 years of age, an total serum IgE at 9 months, 6 years, and 11 years of age. Results: Children living in households with greater than or equal to1 indoor dogs at birth were less likely to develop frequent wheeze than those not having indoor dogs (P = .004). This inverse association was confined to children without parental asthma (hazard ratio = 0.47; P < .001 [Cox regression]) and was not evident for children with parental asthma (hazard ratio = 0.96; P = .87). Adjustment by potential confounders did not change the results. Indoor cat exposure was not significantly associated with the risk of frequent wheezing. Neither cat exposure in early life nor dog exposure in early life was associated with skin prick test reactivity or total serum IgE at any age. Conclusion: Dog exposure in early life might prevent the development of asthmalike symptoms, at least in low-risk children with no family history of asthma. Nevertheless, early pet exposure does not seem to significantly influence the development of allergic sensitization.. asthma| wheezing| atopy| allergy| epidemiology| risk| children| cat| dog| pets| ige|hay-fever| allergic sensitization| children| asthma| environment| prevalence| childhood| community| farmers| cohort.	OCT-2001	asthma| wheezing| atopy| allergy| epidemiology| risk| children| cat| dog| pets| ige|hay-fever| allergic sensitization| children| asthma| environment| prevalence| childhood| community| farmers| cohort	Remes, ST; Castro-Rodriguez, JA; Holberg, CJ; Martinez, FD; Wright, AL	Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; wheezing; atopy; allergy; epidemiology; risk; children; cat; dog; pets; IgE	HAY-FEVER; ALLERGIC SENSITIZATION; CHILDREN; ASTHMA; ENVIRONMENT; PREVALENCE; CHILDHOOD; COMMUNITY; FARMERS; COHORT	Background: Influence of household pets in the development of childhood asthma or atopy has been controversial. Objective: The purpose of this study was to investigate whether pet exposure in early life decreases the subsequent risk of frequent wheezing and/or allergic sensitization. Methods: This was a prospective observational birth cohort study. The setting was a large health maintenance organization in Tucson, Ariz; the subjects were a population sample of 1246 newborns enrolled at birth and followed prospectively to age 13 years. The main outcome measures were as follows: time to first report of frequent wheezing (>3 episodes in the past year), skin prick test reactivity at 6 years and 11 years of age, an total serum IgE at 9 months, 6 years, and 11 years of age. Results: Children living in households with greater than or equal to1 indoor dogs at birth were less likely to develop frequent wheeze than those not having indoor dogs (P = .004). This inverse association was confined to children without parental asthma (hazard ratio = 0.47; P < .001 [Cox regression]) and was not evident for children with parental asthma (hazard ratio = 0.96; P = .87). Adjustment by potential confounders did not change the results. Indoor cat exposure was not significantly associated with the risk of frequent wheezing. Neither cat exposure in early life nor dog exposure in early life was associated with skin prick test reactivity or total serum IgE at any age. Conclusion: Dog exposure in early life might prevent the development of asthmalike symptoms, at least in low-risk children with no family history of asthma. Nevertheless, early pet exposure does not seem to significantly influence the development of allergic sensitization.	30	183	2001	7	10.1067/mai.2001.117797	Allergy; Immunology
Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Background Incidence of asthma increases during early adulthood. We aimed to estimate the contributions of sex and early life factors to asthma diagnosed in young adults. Methods 1246 healthy newborn babies were enrolled in the Tucson Children's Respiratory Study. Parental characteristics, early-life wheezing phenotypes, airway function, and bronchial hyper-responsiveness to cold dry air and sensitisation to Alternaria alternata were determined before age 6 years. Physician-diagnosed asthma, both chronic and newly diagnosed, and airway function were recorded at age 22 years. Findings Of 1246 babies enrolled, 849 had follow-up data at 22 years. Average incidence of asthma at age 16-22 years was 12.6 per thousand person-years. 49 (27%) of all 181 cases of active asthma at 22 years were newly diagnosed, of which 35 (71%) were women. Asthma remittance by 22 years was higher in men than in women (multinomial odds ratio [M-OR] 2.0, 95% CI 1.2-3.2, p=0 . 008). Age at diagnosis was linearly associated with the ratio of forced expiratory volume at 1 s to forced vital capacity at age 22 years. Factors independently associated with chronic asthma at 22 years included onset at 6 years (7.4, 3 . 9-14. 0) and persistent wheezing (14.0, 6.8-28 . 0) in early life, sensitisation to A alternata (3.6, 2.1-6.4), low airway function at age 6 years (2.1, 1.1-3.9.), and bronchial hyper-responsiveness at 6 years (4 . 5, 1.9-10 . 0). Bronchial hyper-responsiveness (6.9, 2.3-21 . 0), low airway function at 6 years (2.8, 1.1-6.9), and late-onset (4 . 6, 1.7-12 . 0) and persistent wheezing (4 . 0, 1.2-14. 0) predicted newly diagnosed asthma at age 22 years. Interpretation Asthma with onset in early adulthood has its origins in early childhood. Funding National Heart Lung and Blood Institute.. young-adults| risk-factors| follow-up| population| life| children| illness| allergen| ratio.	SEP 20-2008	young-adults| risk-factors| follow-up| population| life| children| illness| allergen| ratio	Stern, DA; Morgan, WJ; Halonen, M; Wright, AL; Martinez, FD	Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study		LANCET		YOUNG-ADULTS; RISK-FACTORS; FOLLOW-UP; POPULATION; LIFE; CHILDREN; ILLNESS; ALLERGEN; RATIO	Background Incidence of asthma increases during early adulthood. We aimed to estimate the contributions of sex and early life factors to asthma diagnosed in young adults. Methods 1246 healthy newborn babies were enrolled in the Tucson Children's Respiratory Study. Parental characteristics, early-life wheezing phenotypes, airway function, and bronchial hyper-responsiveness to cold dry air and sensitisation to Alternaria alternata were determined before age 6 years. Physician-diagnosed asthma, both chronic and newly diagnosed, and airway function were recorded at age 22 years. Findings Of 1246 babies enrolled, 849 had follow-up data at 22 years. Average incidence of asthma at age 16-22 years was 12.6 per thousand person-years. 49 (27%) of all 181 cases of active asthma at 22 years were newly diagnosed, of which 35 (71%) were women. Asthma remittance by 22 years was higher in men than in women (multinomial odds ratio [M-OR] 2.0, 95% CI 1.2-3.2, p=0 . 008). Age at diagnosis was linearly associated with the ratio of forced expiratory volume at 1 s to forced vital capacity at age 22 years. Factors independently associated with chronic asthma at 22 years included onset at 6 years (7.4, 3 . 9-14. 0) and persistent wheezing (14.0, 6.8-28 . 0) in early life, sensitisation to A alternata (3.6, 2.1-6.4), low airway function at age 6 years (2.1, 1.1-3.9.), and bronchial hyper-responsiveness at 6 years (4 . 5, 1.9-10 . 0). Bronchial hyper-responsiveness (6.9, 2.3-21 . 0), low airway function at 6 years (2.8, 1.1-6.9), and late-onset (4 . 6, 1.7-12 . 0) and persistent wheezing (4 . 0, 1.2-14. 0) predicted newly diagnosed asthma at age 22 years. Interpretation Asthma with onset in early adulthood has its origins in early childhood. Funding National Heart Lung and Blood Institute.	27	182	2008	7	10.1016/S0140-6736(08)61447-6	General & Internal Medicine
Reduced lung function at birth and the risk of asthma at 10 years of age. BACKGROUND Reduced lung function in early infancy has been associated with later obstructive airway diseases. We assessed whether reduced lung function shortly after birth predicts asthma 10 years later. METHODS We conducted a prospective birth cohort study of healthy infants in which we measured lung function shortly after birth with the use of tidal breathing flow-volume loops (the fraction of expiratory time to peak tidal expiratory flow to total expiratory time [t(sub PTEF)/t(sub E)]) in 802 infants and passive respiratory mechanics, including respiratory-system compliance, in 664 infants. At 10 years of age, 616 children (77%) were reassessed by measuring lung function, exercise-induced bronchoconstriction, and bronchial hyperresponsiveness (by means of a methacholine challenge) and by conducting a structured interview to determine whether there was a history of asthma or current asthma. RESULTS As compared with children whose t(sub PTEF)/t(sub E) shortly after birth was above the median, children whose t(sub PTEF)/t(sub E) was at or below the median were more likely at 10 years of age to have a history of asthma (24.3% vs. 16.2%, P=0.01), to have current asthma (14.6% vs. 7.5%, P=0.005), and to have severe bronchial hyperresponsiveness, defined as a methacholine dose of less than 1.0 micromol causing a 20% fall in the forced expiratory volume in 1 second (FEV(sub 1)) (9.1% vs. 4.9%, P=0.05). As compared with children whose respiratory-system compliance was above the median, children with respiratory compliance at or below the median more often had a history of asthma (27.4% vs. 14.8%; P=0.001) and current asthma (15.0% vs. 7.7%, P=0.009), although this measure was not associated with later measurements of lung function. At 10 years of age, t(sub PTEF)/t(sub E) at birth correlated weakly with the maximal midexpiratory flow rate (r=0.10, P=0.01) but not with FEV(sub 1) or forced vital capacity. CONCLUSIONS Reduced lung function at birth is associated with an increased risk of asthma by 10 years of age.. expiratory flow patterns| bronchial obstruction| airway function| early-life| infants| children| mechanics| exposure| wheeze.	OCT 19-2006	expiratory flow patterns| bronchial obstruction| airway function| early-life| infants| children| mechanics| exposure| wheeze	Haland, G; Carlsen, KCL; Sandvik, L; Devulapalli, CS; Munthe-Kaas, MC; Pettersen, M; Carlsen, KH	Reduced lung function at birth and the risk of asthma at 10 years of age		NEW ENGLAND JOURNAL OF MEDICINE		EXPIRATORY FLOW PATTERNS; BRONCHIAL OBSTRUCTION; AIRWAY FUNCTION; EARLY-LIFE; INFANTS; CHILDREN; MECHANICS; EXPOSURE; WHEEZE	BACKGROUND Reduced lung function in early infancy has been associated with later obstructive airway diseases. We assessed whether reduced lung function shortly after birth predicts asthma 10 years later. METHODS We conducted a prospective birth cohort study of healthy infants in which we measured lung function shortly after birth with the use of tidal breathing flow-volume loops (the fraction of expiratory time to peak tidal expiratory flow to total expiratory time [t(sub PTEF)/t(sub E)]) in 802 infants and passive respiratory mechanics, including respiratory-system compliance, in 664 infants. At 10 years of age, 616 children (77%) were reassessed by measuring lung function, exercise-induced bronchoconstriction, and bronchial hyperresponsiveness (by means of a methacholine challenge) and by conducting a structured interview to determine whether there was a history of asthma or current asthma. RESULTS As compared with children whose t(sub PTEF)/t(sub E) shortly after birth was above the median, children whose t(sub PTEF)/t(sub E) was at or below the median were more likely at 10 years of age to have a history of asthma (24.3% vs. 16.2%, P=0.01), to have current asthma (14.6% vs. 7.5%, P=0.005), and to have severe bronchial hyperresponsiveness, defined as a methacholine dose of less than 1.0 micromol causing a 20% fall in the forced expiratory volume in 1 second (FEV(sub 1)) (9.1% vs. 4.9%, P=0.05). As compared with children whose respiratory-system compliance was above the median, children with respiratory compliance at or below the median more often had a history of asthma (27.4% vs. 14.8%; P=0.001) and current asthma (15.0% vs. 7.7%, P=0.009), although this measure was not associated with later measurements of lung function. At 10 years of age, t(sub PTEF)/t(sub E) at birth correlated weakly with the maximal midexpiratory flow rate (r=0.10, P=0.01) but not with FEV(sub 1) or forced vital capacity. CONCLUSIONS Reduced lung function at birth is associated with an increased risk of asthma by 10 years of age.	25	182	2006	8	10.1056/NEJMoa052885	General & Internal Medicine
Definition, epidemiology and natural history of COPD. Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/ complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for alpha(1)-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.. air pollution| chronic obstructive pulmonary disease clinical/basic investigations| cor pulmonale| epidemiology of asthma/chronic obstructive pulmonary disease| smoking| spirometry|obstructive pulmonary-disease| general-population sample| particulate air-pollution| percutaneous coronary intervention| domiciliary oxygen-therapy| proportional venn-diagram| forced expiratory volume| physician-diagnosed copd| health-care utilization| lung-function decline.	NOV-2007	air pollution| chronic obstructive pulmonary disease clinical/basic investigations| cor pulmonale| epidemiology of asthma/chronic obstructive pulmonary disease| smoking| spirometry|obstructive pulmonary-disease| general-population sample| particulate air-pollution| percutaneous coronary intervention| domiciliary oxygen-therapy| proportional venn-diagram| forced expiratory volume| physician-diagnosed copd| health-care utilization| lung-function decline	Viegi, G; Pistelli, F; Sherrill, DL; Maio, S; Baldacci, S; Carrozzi, L	Definition, epidemiology and natural history of COPD		EUROPEAN RESPIRATORY JOURNAL	air pollution; chronic obstructive pulmonary disease clinical/basic investigations; cor pulmonale; epidemiology of asthma/chronic obstructive pulmonary disease; smoking; spirometry	OBSTRUCTIVE PULMONARY-DISEASE; GENERAL-POPULATION SAMPLE; PARTICULATE AIR-POLLUTION; PERCUTANEOUS CORONARY INTERVENTION; DOMICILIARY OXYGEN-THERAPY; PROPORTIONAL VENN-DIAGRAM; FORCED EXPIRATORY VOLUME; PHYSICIAN-DIAGNOSED COPD; HEALTH-CARE UTILIZATION; LUNG-FUNCTION DECLINE	Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/ complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for alpha(1)-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.	221	181	2007	21	10.1183/09031936.00082507	Respiratory System
Literature review of Florida red tide: implications for human health effects. Florida red tides are a natural phenomenon caused by dense aggregations of single cell or several species Of unicellular organisms. Patches of discolored water, dead or dying fish, and respiratory irritants in the air often characterize these algal blooms. In humans, two distinct clinical entities, depending on the route of exposure, are associated with exposure to the Florida red tide toxins (particularly the brevetoxins). With the ingestion of brevetoxin-contaminated shellfish, neurotoxic shellfish poisoning (NSP) presents as a milder gastroenteritis with neurologic symptoms compared with other marine toxin diseases such as paralytic shellfish poisoning (PSP) or ciguatera fish poisoning. With the inhalation of the aerosolized red tide toxins (especially the brevetoxins) from the sea spray, respiratory irritation and possibly other health effects are reported in both humans and other mammals [Nat. Toxins Drugs (1995) 141; Fleming, L.E., Baden, D.G., 1988. Neurotoxic shellfish poisoning: public health and human health effects. White Paper for the Proceedings of the Texas Conference on Neurotoxic Shellfish Poisoning. In: Proceedings of the Texas NSP Conference, Corpus Christi, TX, pp. 27-34; Travel Med, 2 (10) (1998b) 1: Travel Med. 3 (10) (1999a) 1; Toxins Pathol. 26 (2) (1998) 276; J. Allergy Clin. Imunol. 69 (1982) 418; Arch. Intern. Med. 149 (1989) 1735; Toxicon 24 (1986) 955; Florida Med. J. 60 (11) (1773) 27; J. Nat. Toxins 4 (1995) 181; J. Nat. Toxins 4 (1995) 18 1: Sci. Ani. 271 (4) (1994) 62]. This paper reviews the literature on the known and possible human health effects of exposure to the Florida red tides and their toxins. The review includes discussion of the red tide organisms and their toxins, as well as the effects of these toxins on both wild and laboratory animals as they relate to possible human health effects and exposures. (C) 2004 Elsevier B.V. All rights reserved.. florida red tide| red tide| neurotoxic shellfish poisoning| nsp| brevetoxins| harmful algal bloom| hab| karenia brevis| shellfish poisoning| respiratory irritation| marine toxin diseases|neurotoxic shellfish toxins| formerly gymnodinium-breve| sensitive sodium-channels| rat-brain synaptosomes| marine algal toxins| ptychodiscus-brevis| new-zealand| dinoflagellate toxins| crassostrea-gigas| mouse bioassay.	APR-2004	florida red tide| red tide| neurotoxic shellfish poisoning| nsp| brevetoxins| harmful algal bloom| hab| karenia brevis| shellfish poisoning| respiratory irritation| marine toxin diseases|neurotoxic shellfish toxins| formerly gymnodinium-breve| sensitive sodium-channels| rat-brain synaptosomes| marine algal toxins| ptychodiscus-brevis| new-zealand| dinoflagellate toxins| crassostrea-gigas| mouse bioassay	Kirkpatrick, B; Fleming, LE; Squicciarini, D; Backer, LC; Clark, R; Abraham, W; Benson, J; Cheng, YS; Johnson, D; Pierce, R; Zaias, J; Bossart, GD; Baden, DG	Literature review of Florida red tide: implications for human health effects		HARMFUL ALGAE	Florida red tide; red tide; neurotoxic shellfish poisoning; NSP; brevetoxins; harmful algal bloom; HAB; karenia brevis; shellfish poisoning; respiratory irritation; marine toxin diseases	NEUROTOXIC SHELLFISH TOXINS; FORMERLY GYMNODINIUM-BREVE; SENSITIVE SODIUM-CHANNELS; RAT-BRAIN SYNAPTOSOMES; MARINE ALGAL TOXINS; PTYCHODISCUS-BREVIS; NEW-ZEALAND; DINOFLAGELLATE TOXINS; CRASSOSTREA-GIGAS; MOUSE BIOASSAY	Florida red tides are a natural phenomenon caused by dense aggregations of single cell or several species Of unicellular organisms. Patches of discolored water, dead or dying fish, and respiratory irritants in the air often characterize these algal blooms. In humans, two distinct clinical entities, depending on the route of exposure, are associated with exposure to the Florida red tide toxins (particularly the brevetoxins). With the ingestion of brevetoxin-contaminated shellfish, neurotoxic shellfish poisoning (NSP) presents as a milder gastroenteritis with neurologic symptoms compared with other marine toxin diseases such as paralytic shellfish poisoning (PSP) or ciguatera fish poisoning. With the inhalation of the aerosolized red tide toxins (especially the brevetoxins) from the sea spray, respiratory irritation and possibly other health effects are reported in both humans and other mammals [Nat. Toxins Drugs (1995) 141; Fleming, L.E., Baden, D.G., 1988. Neurotoxic shellfish poisoning: public health and human health effects. White Paper for the Proceedings of the Texas Conference on Neurotoxic Shellfish Poisoning. In: Proceedings of the Texas NSP Conference, Corpus Christi, TX, pp. 27-34; Travel Med, 2 (10) (1998b) 1: Travel Med. 3 (10) (1999a) 1; Toxins Pathol. 26 (2) (1998) 276; J. Allergy Clin. Imunol. 69 (1982) 418; Arch. Intern. Med. 149 (1989) 1735; Toxicon 24 (1986) 955; Florida Med. J. 60 (11) (1773) 27; J. Nat. Toxins 4 (1995) 181; J. Nat. Toxins 4 (1995) 18 1: Sci. Ani. 271 (4) (1994) 62]. This paper reviews the literature on the known and possible human health effects of exposure to the Florida red tides and their toxins. The review includes discussion of the red tide organisms and their toxins, as well as the effects of these toxins on both wild and laboratory animals as they relate to possible human health effects and exposures. (C) 2004 Elsevier B.V. All rights reserved.	147	181	2004	17	10.1016/j.hal.2003.08.005	Marine & Freshwater Biology
Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant. Background In May 2000, eight persons who had formerly worked at a microwave-popcorn production plant were reported to have severe bronchiolitis obliterans. No recognized cause was identified in the plant. Therefore, we medically evaluated current employees and assessed their occupational exposures. Methods Questionnaire responses and spirometric findings in participating workers were compared with data from the third National Health and Nutrition Examination Survey, after adjustment for age and smoking status. We evaluated the relation between exposures and health-related outcomes by analyzing the rates of symptoms and abnormalities according to current and cumulative exposure to diacetyl, the predominant ketone in artificial butter flavoring and in the air at the plant. Results Of the 135 current workers at the plant, 117 (87 percent) completed the questionnaire. These 117 workers had 2.6 times the expected rates of chronic cough and shortness of breath, according to comparisons with the national data, and twice the expected rates of physician-diagnosed asthma and chronic bronchitis. Overall, the workers had 3.3 times the expected rate of airway obstruction; those who had never smoked had 10.8 times the expected rate. Workers directly involved in the production of microwave popcorn had higher rates of shortness of breath on exertion and skin problems that had developed since they started work than workers in other parts of the plant. There was a strong relation between the quartile of estimated cumulative exposure to diacetyl and the frequency and extent of airway obstruction. Conclusions The excess rates of lung disease and lung-function abnormalities and the relation between exposure and outcomes in this working population indicate that they probably had occupational bronchiolitis obliterans caused by the inhalation of volatile butter-flavoring ingredients.. population| values| sample.	AUG 1-2002	population| values| sample	Kreiss, K; Gomaa, A; Kullman, G; Fedan, K; Simoes, EJ; Enright, PL	Clinical bronchiolitis obliterans in workers at a microwave-popcorn plant		NEW ENGLAND JOURNAL OF MEDICINE		POPULATION; VALUES; SAMPLE	Background In May 2000, eight persons who had formerly worked at a microwave-popcorn production plant were reported to have severe bronchiolitis obliterans. No recognized cause was identified in the plant. Therefore, we medically evaluated current employees and assessed their occupational exposures. Methods Questionnaire responses and spirometric findings in participating workers were compared with data from the third National Health and Nutrition Examination Survey, after adjustment for age and smoking status. We evaluated the relation between exposures and health-related outcomes by analyzing the rates of symptoms and abnormalities according to current and cumulative exposure to diacetyl, the predominant ketone in artificial butter flavoring and in the air at the plant. Results Of the 135 current workers at the plant, 117 (87 percent) completed the questionnaire. These 117 workers had 2.6 times the expected rates of chronic cough and shortness of breath, according to comparisons with the national data, and twice the expected rates of physician-diagnosed asthma and chronic bronchitis. Overall, the workers had 3.3 times the expected rate of airway obstruction; those who had never smoked had 10.8 times the expected rate. Workers directly involved in the production of microwave popcorn had higher rates of shortness of breath on exertion and skin problems that had developed since they started work than workers in other parts of the plant. There was a strong relation between the quartile of estimated cumulative exposure to diacetyl and the frequency and extent of airway obstruction. Conclusions The excess rates of lung disease and lung-function abnormalities and the relation between exposure and outcomes in this working population indicate that they probably had occupational bronchiolitis obliterans caused by the inhalation of volatile butter-flavoring ingredients.	19	181	2002	9	10.1056/NEJMoa020300	General & Internal Medicine
House dust mite and cockroach exposure are strong risk factors for positive allergy skin test responses in the Childhood Asthma Management Program. Background: Children with asthma have a high prevalence of environmental allergies, especially to indoor allergens. The relationships of exposure to indoor allergens (dust mites, cat, dog, cockroach, and molds) and other host factors to allergy sensitization have not been evaluated simultaneously in a large cohort. Objectives: We studied 1041 children aged 5 to 12 years with mild-to-moderate asthma to determine risk factors associated with having positive allergy skin test responses to indoor allergens. Also, we described, compared, and contrasted 6 allergens in the home environments of these children from 8 North American cities. Methods: Data were used from baseline visits of the Childhood Asthma Management Program. Patients' sensitivities to house dust mites (Dermatophagoides farinae and Dermatophagoides pteronyssinus), cats, dogs, cockroaches, and molds were examined for relationships to demographic variables, home dust allergen exposures, number of other positive allergy skin test responses, total serum IgE levels, and smoking in the home. Results: San Diego (78.5%) and Toronto (59.3%) had the topmost percentages of homes with moderate-to-high house dust mite levels. Boston (21.5%), St Louis (16.3%), and Baltimore (13.4%) had the highest percentages of homes with detectable levels of cockroach allergen. For house dust mites, the higher the level of allergen exposure, the more likely patients were to have positive allergy skin test responses, with relative odds of 9.0 (95% confidence interval, 5.4-15.1) for those exposed to high mite levels: (>10.0 mug/g dust) relative to those unexposed. Even exposure to low levels of mite allergen (0.020-2.0 mug/g) was found to be a significant risk factor for sensitization. For cockroach allergen, those with detectable home exposure were more likely to have positive skin test responses (relative odds, 2.2; 95% confidence interval, 1.3-3.8) than those with undetectable exposure. In contrast, levels of exposure to cat, dog, and mold allergens were not related to sensitization rates. For cat allergen, this may reflect lower rates of cat ownership among highly sensitized subjects. Furthermore, the number of allergy skin test responses that were positive, excluding the test for the outcome of interest for each model, and total serum IgE levels were strong independent predictors of sensitization. Conclusions: Levels of exposure determined by house dust analysis are important determinants of sensitization for dust mite and cockroach allergen. This relationship was not demonstrable for cat, dog, or mold allergens, possibly because of confounding factors. For all allergens studied, the degree of atopy; determined by the total number of positive skin test responses or by total serum IgE levels, is an important contributing risk factor for sensitization.. house dust mites| childhood asthma| cockroach allergy| childhood asthma management program| allergy sensitization| indoor allergens| atopy| risk factors for asthma| allergen exposure|inner-city children| cat allergen| sensitization| homes| australia| antigen| school| dog.	JAN-2001	house dust mites| childhood asthma| cockroach allergy| childhood asthma management program| allergy sensitization| indoor allergens| atopy| risk factors for asthma| allergen exposure|inner-city children| cat allergen| sensitization| homes| australia| antigen| school| dog	Huss, K; Adkinson, NF; Eggleston, PA; Dawson, C; Van Natta, ML; Hamilton, RG	House dust mite and cockroach exposure are strong risk factors for positive allergy skin test responses in the Childhood Asthma Management Program		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	house dust mites; childhood asthma; cockroach allergy; Childhood Asthma Management Program; allergy sensitization; indoor allergens; atopy; risk factors for asthma; allergen exposure	INNER-CITY CHILDREN; CAT ALLERGEN; SENSITIZATION; HOMES; AUSTRALIA; ANTIGEN; SCHOOL; DOG	Background: Children with asthma have a high prevalence of environmental allergies, especially to indoor allergens. The relationships of exposure to indoor allergens (dust mites, cat, dog, cockroach, and molds) and other host factors to allergy sensitization have not been evaluated simultaneously in a large cohort. Objectives: We studied 1041 children aged 5 to 12 years with mild-to-moderate asthma to determine risk factors associated with having positive allergy skin test responses to indoor allergens. Also, we described, compared, and contrasted 6 allergens in the home environments of these children from 8 North American cities. Methods: Data were used from baseline visits of the Childhood Asthma Management Program. Patients' sensitivities to house dust mites (Dermatophagoides farinae and Dermatophagoides pteronyssinus), cats, dogs, cockroaches, and molds were examined for relationships to demographic variables, home dust allergen exposures, number of other positive allergy skin test responses, total serum IgE levels, and smoking in the home. Results: San Diego (78.5%) and Toronto (59.3%) had the topmost percentages of homes with moderate-to-high house dust mite levels. Boston (21.5%), St Louis (16.3%), and Baltimore (13.4%) had the highest percentages of homes with detectable levels of cockroach allergen. For house dust mites, the higher the level of allergen exposure, the more likely patients were to have positive allergy skin test responses, with relative odds of 9.0 (95% confidence interval, 5.4-15.1) for those exposed to high mite levels: (>10.0 mug/g dust) relative to those unexposed. Even exposure to low levels of mite allergen (0.020-2.0 mug/g) was found to be a significant risk factor for sensitization. For cockroach allergen, those with detectable home exposure were more likely to have positive skin test responses (relative odds, 2.2; 95% confidence interval, 1.3-3.8) than those with undetectable exposure. In contrast, levels of exposure to cat, dog, and mold allergens were not related to sensitization rates. For cat allergen, this may reflect lower rates of cat ownership among highly sensitized subjects. Furthermore, the number of allergy skin test responses that were positive, excluding the test for the outcome of interest for each model, and total serum IgE levels were strong independent predictors of sensitization. Conclusions: Levels of exposure determined by house dust analysis are important determinants of sensitization for dust mite and cockroach allergen. This relationship was not demonstrable for cat, dog, or mold allergens, possibly because of confounding factors. For all allergens studied, the degree of atopy; determined by the total number of positive skin test responses or by total serum IgE levels, is an important contributing risk factor for sensitization.	32	181	2001	7	10.1067/mai.2001.111146	Allergy; Immunology
Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method. Background: Sublingual immunotherapy (SLIT) is effective and safe in the treatment of allergic rhinitis. However, there is no meta-analysis in asthma treatment. Methods: The clinical efficacy of SLIT for asthma was evaluated through a systematic review with meta-analysis. MEDLINE (1966-2005), EMBASE (1974-2005), LILACS (1982-2005), and the Cochrane Library were searched for related literature in any language. Randomized-controlled clinical trials (RCT) on SLIT in asthma treatment for adults and children were selected. From 119 citations, 25 studies with 1706 patients were included in this meta-analysis. For each report, quality scores were assigned and data were extracted in relation to the outcomes analyzed: asthmatic symptoms, use of asthma medications, lung function, and bronchial provocation. Results: According to the Jadad quality method, 64% of the studies were assigned scores of 4 or 5. Immunotherapy was seen to significantly reduce asthma severity when parameter compositions were all analyzed by categorical outcomes. There was a nonsignificant reduction in asthma symptoms when analyzed using standardized mean differences. No severe reactions were observed. Conclusions: This meta-analysis found that SLIT is beneficial for asthma treatment albeit the magnitude of the effect is not very large. Moreover, it is a safe alternative to the subcutaneous route. More RCT with standardization of symptom scores and medications are needed in order to contribute further to this subject.. asthma| immunotherapy| meta-analysis| review| sublingual|placebo-controlled trial| double-blind placebo| grass-pollen extract| house-dust mites| standardized 5-grass-pollen extract| swallow immunotherapy| allergic rhinoconjunctivitis| respiratory allergy| bronchial hyperreactivity| pediatric-patients.	OCT-2006	asthma| immunotherapy| meta-analysis| review| sublingual|placebo-controlled trial| double-blind placebo| grass-pollen extract| house-dust mites| standardized 5-grass-pollen extract| swallow immunotherapy| allergic rhinoconjunctivitis| respiratory allergy| bronchial hyperreactivity| pediatric-patients	Calamita, Z; Saconato, H; Pela, AB; Atallah, AN	Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method		ALLERGY	asthma; immunotherapy; meta-analysis; review; sublingual	PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND PLACEBO; GRASS-POLLEN EXTRACT; HOUSE-DUST MITES; STANDARDIZED 5-GRASS-POLLEN EXTRACT; SWALLOW IMMUNOTHERAPY; ALLERGIC RHINOCONJUNCTIVITIS; RESPIRATORY ALLERGY; BRONCHIAL HYPERREACTIVITY; PEDIATRIC-PATIENTS	Background: Sublingual immunotherapy (SLIT) is effective and safe in the treatment of allergic rhinitis. However, there is no meta-analysis in asthma treatment. Methods: The clinical efficacy of SLIT for asthma was evaluated through a systematic review with meta-analysis. MEDLINE (1966-2005), EMBASE (1974-2005), LILACS (1982-2005), and the Cochrane Library were searched for related literature in any language. Randomized-controlled clinical trials (RCT) on SLIT in asthma treatment for adults and children were selected. From 119 citations, 25 studies with 1706 patients were included in this meta-analysis. For each report, quality scores were assigned and data were extracted in relation to the outcomes analyzed: asthmatic symptoms, use of asthma medications, lung function, and bronchial provocation. Results: According to the Jadad quality method, 64% of the studies were assigned scores of 4 or 5. Immunotherapy was seen to significantly reduce asthma severity when parameter compositions were all analyzed by categorical outcomes. There was a nonsignificant reduction in asthma symptoms when analyzed using standardized mean differences. No severe reactions were observed. Conclusions: This meta-analysis found that SLIT is beneficial for asthma treatment albeit the magnitude of the effect is not very large. Moreover, it is a safe alternative to the subcutaneous route. More RCT with standardization of symptom scores and medications are needed in order to contribute further to this subject.	87	180	2006	11	10.1111/j.1395-9995.2006.01205.x	Allergy; Immunology
Maternal and grandmaternal smoking patterns are associated with early childhood asthma. Objective: To investigate the associations of maternal and grandmaternal smoking before, during, and after pregnancy with childhood asthma. Design, setting, and participants: We conducted a case-control study nested within the Children's Health Study in southern California. The case patients consisted of 338 children with asthma that had been diagnosed in the first 5 years of life, and 570 control subjects were countermatched on in utero exposure to maternal smoking within grade, sex, and community of residence. Measurements: Detailed maternal and household smoking histories and other asthma risk factor information was obtained by telephone interview. Results: The participation rates were 72.3% and S2.5%, respectively, for control subjects and case patients. In utero exposure to maternal smoking was associated with increased risk for asthma diagnosed in the first 5 years of life (odds ratio [OR], 1.5; 95% confidence interval [CI] 1.0 to 2.3), and for persistent asthma (OR, 1.5; 95% CI, 1.0 to 2.3). The associations did not differ in children with early transient asthma compared to those with early persistent asthma. Relative to never-smokers, children whose mothers smoked throughout the pregnancy had an elevated risk of asthma in the first 5 years of life (OR, 1.6; 95% CI, 1.0 to 2.6). Children of mothers who quit smoking prior to the pregnancy showed no increased risk (OR, 0.9; 95% CI, 0.5 to 1.5). We were unable to assess the association of smoking cessation during pregnancy because very few mothers were reported to have done so (15%). Asthma risk did not increase in a monotonic pattern with smoking intensity during pregnancy. Postnatal secondhand smoke exposure was not independently associated with asthma. Grandmaternal smoking during the mother's fetal period was associated with increased asthma risk in her grandchildren (OR, 2.1; 95% CI, 1.4 to 3.2). Conclusions: Maternal and grandmaternal smoking during pregnancy may increase the risk of childhood asthma.. asthma| in utero exposure to maternal smoking| smoking cessation| transgenerational association|environmental tobacco-smoke| southern california communities| parental smoking| allergic rhinoconjunctivitis| respiratory-function| differing levels| family-history| air-pollution| atopic eczema| united-states.	APR-2005	asthma| in utero exposure to maternal smoking| smoking cessation| transgenerational association|environmental tobacco-smoke| southern california communities| parental smoking| allergic rhinoconjunctivitis| respiratory-function| differing levels| family-history| air-pollution| atopic eczema| united-states	Li, YF; Langholz, B; Salam, MT; Gilliland, FD	Maternal and grandmaternal smoking patterns are associated with early childhood asthma		CHEST	asthma; in utero exposure to maternal smoking; smoking cessation; transgenerational association	ENVIRONMENTAL TOBACCO-SMOKE; SOUTHERN CALIFORNIA COMMUNITIES; PARENTAL SMOKING; ALLERGIC RHINOCONJUNCTIVITIS; RESPIRATORY-FUNCTION; DIFFERING LEVELS; FAMILY-HISTORY; AIR-POLLUTION; ATOPIC ECZEMA; UNITED-STATES	Objective: To investigate the associations of maternal and grandmaternal smoking before, during, and after pregnancy with childhood asthma. Design, setting, and participants: We conducted a case-control study nested within the Children's Health Study in southern California. The case patients consisted of 338 children with asthma that had been diagnosed in the first 5 years of life, and 570 control subjects were countermatched on in utero exposure to maternal smoking within grade, sex, and community of residence. Measurements: Detailed maternal and household smoking histories and other asthma risk factor information was obtained by telephone interview. Results: The participation rates were 72.3% and S2.5%, respectively, for control subjects and case patients. In utero exposure to maternal smoking was associated with increased risk for asthma diagnosed in the first 5 years of life (odds ratio [OR], 1.5; 95% confidence interval [CI] 1.0 to 2.3), and for persistent asthma (OR, 1.5; 95% CI, 1.0 to 2.3). The associations did not differ in children with early transient asthma compared to those with early persistent asthma. Relative to never-smokers, children whose mothers smoked throughout the pregnancy had an elevated risk of asthma in the first 5 years of life (OR, 1.6; 95% CI, 1.0 to 2.6). Children of mothers who quit smoking prior to the pregnancy showed no increased risk (OR, 0.9; 95% CI, 0.5 to 1.5). We were unable to assess the association of smoking cessation during pregnancy because very few mothers were reported to have done so (15%). Asthma risk did not increase in a monotonic pattern with smoking intensity during pregnancy. Postnatal secondhand smoke exposure was not independently associated with asthma. Grandmaternal smoking during the mother's fetal period was associated with increased asthma risk in her grandchildren (OR, 2.1; 95% CI, 1.4 to 3.2). Conclusions: Maternal and grandmaternal smoking during pregnancy may increase the risk of childhood asthma.	44	180	2005	10	10.1378/chest.127.4.1232	General & Internal Medicine; Respiratory System
The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study: Design and first results. The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study was initiated in 1996. Children born to allergic mothers were enrolled in a double-blind placebo-controlled trial for evaluating the use of mite-impermeable mattress and pillow covers. Children born to allergic and non-allergic mothers were enrolled in a 'natural history' study to assess the role of environmental and dietary risk factors for the development of allergic disease in childhood. Recruitment started by distributing a validated screening questionnaire among >10,000 pregnant women during their first visit to a prenatal health clinic. Allergic mothers-to-be were invited to participate in the intervention study. Allergic, and a random sample of non-allergic, mothers-to-be were invited to participate in the 'natural history' arm of the study. In the intervention study, homes were visited before birth, 3 months after birth, and 12 months after birth for the collection of dust samples from floors and mattresses. In addition, the homes of about one-third of the children in the 'natural history' part of the study were visited for dust collection when the children were 3 months of age. The intervention study started with 855 participants and the 'natural history' study with 3,291 participants. Follow-up at 3 years of age has now been completed with satisfactory compliance (>90%,). A medical investigation and home visit at 4 years of age are nearing completion. Preliminary results show that mite-allergen levels were lower than found in previous Dutch studies, and that the intervention measure had a significant effect on mite-allergen levels, without important clinical benefits up to age 2 years old. The allergic families lived in homes with fewer 'triggers' such as pets, smoking and carpets than the non-allergic families, regardless of the intervention. The ongoing PIAMA cohort study will probably reveal useful information concerning effects of allergen load and reduction in the setting of a relatively low mite-allergen exposure, as well as other variables on the development of allergic manifestions and asthma.. allergy| asthma| intervention| natural history| dust mites|house-dust mite| sensitization| exposure| children| environment| avoidance| childhood| infancy| life| risk.	2002	allergy| asthma| intervention| natural history| dust mites|house-dust mite| sensitization| exposure| children| environment| avoidance| childhood| infancy| life| risk	Brunekreef, B; Smit, J; de Jongste, J; Neijens, H; Gerritsen, J; Postma, D; Aalberse, R; Koopman, L; Kerkhof, M; Wijga, A; van Strien, R	The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study: Design and first results		PEDIATRIC ALLERGY AND IMMUNOLOGY	allergy; asthma; intervention; natural history; dust mites	HOUSE-DUST MITE; SENSITIZATION; EXPOSURE; CHILDREN; ENVIRONMENT; AVOIDANCE; CHILDHOOD; INFANCY; LIFE; RISK	The Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study was initiated in 1996. Children born to allergic mothers were enrolled in a double-blind placebo-controlled trial for evaluating the use of mite-impermeable mattress and pillow covers. Children born to allergic and non-allergic mothers were enrolled in a 'natural history' study to assess the role of environmental and dietary risk factors for the development of allergic disease in childhood. Recruitment started by distributing a validated screening questionnaire among >10,000 pregnant women during their first visit to a prenatal health clinic. Allergic mothers-to-be were invited to participate in the intervention study. Allergic, and a random sample of non-allergic, mothers-to-be were invited to participate in the 'natural history' arm of the study. In the intervention study, homes were visited before birth, 3 months after birth, and 12 months after birth for the collection of dust samples from floors and mattresses. In addition, the homes of about one-third of the children in the 'natural history' part of the study were visited for dust collection when the children were 3 months of age. The intervention study started with 855 participants and the 'natural history' study with 3,291 participants. Follow-up at 3 years of age has now been completed with satisfactory compliance (>90%,). A medical investigation and home visit at 4 years of age are nearing completion. Preliminary results show that mite-allergen levels were lower than found in previous Dutch studies, and that the intervention measure had a significant effect on mite-allergen levels, without important clinical benefits up to age 2 years old. The allergic families lived in homes with fewer 'triggers' such as pets, smoking and carpets than the non-allergic families, regardless of the intervention. The ongoing PIAMA cohort study will probably reveal useful information concerning effects of allergen load and reduction in the setting of a relatively low mite-allergen exposure, as well as other variables on the development of allergic manifestions and asthma.	17	180	2002	6	10.1034/j.1399-3038.13.s.15.1.x	Allergy; Immunology; Pediatrics
"Prevalence and etiology of asthma. An increased understanding of the causes of asthma is coming from the international comparisons of asthma prevalence particularly those from the European Community Respiratory Health Survey of asthma prevalence in adults and the International Study of Asthma and Allergies in Childhood. From these and other studies of asthma prevalence, it is possible to draw some tentative conclusions as to the patterns of asthma prevalence worldwide, There are five striking patterns: first, asthma prevalence is increasing worldwide; second, asthma is generally more common in Western countries and less common in developing countries; third, asthma is more prevalent in English-speaking countries; fourth, asthma prevalence is increasing in developing countries as they become more Westernized or communities become urbanized: and fifth, the prevalence of other allergic disorders may also be increasing worldwide. These five key features of the international patterns of asthma prevalence raise major questions about the role of ""established"" risk factors for the development of asthma, As a result, recent research has expanded to include the study of novel factors that may ""program"" the initial susceptibility to sensitization or contribute to the development of asthma independent of atopic sensitization. These include various exposures in utero, which are reflected in various perinatal factors measured at birth, and exposures (or lack of exposures) in the early years of life that may make the infant more susceptible to the subsequent development of asthma, These issues are now the focus of an intensive research effort worldwide, and the next few gears are likely to see exciting advances in our understanding of the causes of asthma.. asthma| prevalence| atopic disorders| isaac| etiology|respiratory-health-survey| childhood asthma| increasing prevalence| written questionnaire| video questionnaire| changing prevalence| risk factor| new-zealand| children| atopy."	FEB-2000	asthma| prevalence| atopic disorders| isaac| etiology|respiratory-health-survey| childhood asthma| increasing prevalence| written questionnaire| video questionnaire| changing prevalence| risk factor| new-zealand| children| atopy	Beasley, R; Crane, J; Lai, CKW; Pearce, N	Prevalence and etiology of asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; prevalence; atopic disorders; ISAAC; etiology	RESPIRATORY-HEALTH-SURVEY; CHILDHOOD ASTHMA; INCREASING PREVALENCE; WRITTEN QUESTIONNAIRE; VIDEO QUESTIONNAIRE; CHANGING PREVALENCE; RISK FACTOR; NEW-ZEALAND; CHILDREN; ATOPY	"An increased understanding of the causes of asthma is coming from the international comparisons of asthma prevalence particularly those from the European Community Respiratory Health Survey of asthma prevalence in adults and the International Study of Asthma and Allergies in Childhood. From these and other studies of asthma prevalence, it is possible to draw some tentative conclusions as to the patterns of asthma prevalence worldwide, There are five striking patterns: first, asthma prevalence is increasing worldwide; second, asthma is generally more common in Western countries and less common in developing countries; third, asthma is more prevalent in English-speaking countries; fourth, asthma prevalence is increasing in developing countries as they become more Westernized or communities become urbanized: and fifth, the prevalence of other allergic disorders may also be increasing worldwide. These five key features of the international patterns of asthma prevalence raise major questions about the role of ""established"" risk factors for the development of asthma, As a result, recent research has expanded to include the study of novel factors that may ""program"" the initial susceptibility to sensitization or contribute to the development of asthma independent of atopic sensitization. These include various exposures in utero, which are reflected in various perinatal factors measured at birth, and exposures (or lack of exposures) in the early years of life that may make the infant more susceptible to the subsequent development of asthma, These issues are now the focus of an intensive research effort worldwide, and the next few gears are likely to see exciting advances in our understanding of the causes of asthma."	65	180	2000	7	10.1016/S0091-6749(00)90044-7	Allergy; Immunology
Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement. Background: A previous American College of Chest Physicians Consensus Statement on asthma in the workplace was published in 1995. The current Consensus Statement updates the previous one based on additional research that has been published since then, including findings relevant to preventive measures and work-exacerbated asthma (WEA). Methods: A panel of experts, including allergists, pulmonologists, and occupational medicine physicians, was convened to develop this Consensus Document on the diagnosis and management of work-related asthma (WRA), based in part on a systematic review, that was performed by the University of Alberta/Capital Health Evidence-Based Practice and was supplemented by additional published studies to 2007. Results: The Consensus Document defined WRA to include occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and WEA (ie, preexisting or concurrent asthma worsened by work factors). The Consensus Document focuses on the diagnosis and management of NIMA (including diagnostic tests, and work and compensation issues), as well as preventive measures. WRA should be considered in all individuals with new-onset or worsening asthma, and a careful occupational history should be obtained. Diagnostic tests such as serial peak flow recordings, methacholine challenge tests, immunologic tests, and specific inhalation challenge tests, (if available), can increase diagnostic certainty. Since the prognosis is better with early diagnosis and appropriate intervention, effective preventive measures for other workers with exposure should be addressed. Conclusions: The substantial prevalence of WRA supports consideration of the diagnosis in all who present with new-onset or worsening asthma, followed by appropriate investigations and intervention including consideration of other exposed workers.. asthma| occupational lung| preventive medicine|exhaled nitric-oxide| peak expiratory flow| natural-rubber latex| health-care workers| induced occupational asthma| diisocyanate-induced asthma| irritant-induced asthma| vocal cord dysfunction| red cedar asthma| nonspecific bronchial hyperresponsiveness.	SEP-2008	asthma| occupational lung| preventive medicine|exhaled nitric-oxide| peak expiratory flow| natural-rubber latex| health-care workers| induced occupational asthma| diisocyanate-induced asthma| irritant-induced asthma| vocal cord dysfunction| red cedar asthma| nonspecific bronchial hyperresponsiveness	Tarlo, SM; Balmes, J; Balkissoon, R; Beach, J; Beckett, W; Bernstein, D; Blanc, PD; Brooks, SM; Cowl, CT; Daroowalla, F; Harber, P; Lemiere, C; Liss, GM; Pacheco, KA; Redlich, CA; Rowe, B; Heitzer, J	Diagnosis and management of work-related asthma: American College of Chest Physicians Consensus Statement		CHEST	asthma; occupational lung; preventive medicine	EXHALED NITRIC-OXIDE; PEAK EXPIRATORY FLOW; NATURAL-RUBBER LATEX; HEALTH-CARE WORKERS; INDUCED OCCUPATIONAL ASTHMA; DIISOCYANATE-INDUCED ASTHMA; IRRITANT-INDUCED ASTHMA; VOCAL CORD DYSFUNCTION; RED CEDAR ASTHMA; NONSPECIFIC BRONCHIAL HYPERRESPONSIVENESS	Background: A previous American College of Chest Physicians Consensus Statement on asthma in the workplace was published in 1995. The current Consensus Statement updates the previous one based on additional research that has been published since then, including findings relevant to preventive measures and work-exacerbated asthma (WEA). Methods: A panel of experts, including allergists, pulmonologists, and occupational medicine physicians, was convened to develop this Consensus Document on the diagnosis and management of work-related asthma (WRA), based in part on a systematic review, that was performed by the University of Alberta/Capital Health Evidence-Based Practice and was supplemented by additional published studies to 2007. Results: The Consensus Document defined WRA to include occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and WEA (ie, preexisting or concurrent asthma worsened by work factors). The Consensus Document focuses on the diagnosis and management of NIMA (including diagnostic tests, and work and compensation issues), as well as preventive measures. WRA should be considered in all individuals with new-onset or worsening asthma, and a careful occupational history should be obtained. Diagnostic tests such as serial peak flow recordings, methacholine challenge tests, immunologic tests, and specific inhalation challenge tests, (if available), can increase diagnostic certainty. Since the prognosis is better with early diagnosis and appropriate intervention, effective preventive measures for other workers with exposure should be addressed. Conclusions: The substantial prevalence of WRA supports consideration of the diagnosis in all who present with new-onset or worsening asthma, followed by appropriate investigations and intervention including consideration of other exposed workers.	304	179	2008	41	10.1378/chest.08-0201	General & Internal Medicine; Respiratory System
Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17. Exposure to ozone, which is a major component of air pollution, induces a form of asthma that occurs in the absence of adaptive immunity. Although ozone-induced asthma is characterized by airway neutrophilia, and not eosinophilia, it is nevertheless associated with airway hyperreactivity (AHR), which is a cardinal feature of asthma. Because AHR induced by allergens requires the presence of natural killer T (NKT) cells, we asked whether ozone-induced AHR had similar requirements. We found that repeated exposure of wild-type (WT) mice to ozone induced severe AHR associated with an increase in airway NKT cells, neutrophils, and macrophages. Surprisingly, NKT cell-deficient (CD1d(-/-) and J alpha 18(-/-)) mice failed to develop ozone-induced AHR. Further, treatment of WT mice with an anti-CD1d mAb blocked NKT cell activation and prevented ozone-induced AHR. Moreover, ozone-induced, but not allergen-induced, AHR was associated with NKT cells producing interleukin (IL)-17, and failed to occur in IL-17(-/-) mice nor in WT mice treated with anti-IL-17 mAb. Thus, ozone exposure induces AHR that requires the presence of NKT cells and IL-17 production. Because NKT cells are required for the development of two very disparate forms of AHR (ozone- and allergen-induced), our results strongly suggest that NKT cells mediate a unifying pathogenic mechanism for several distinct forms of asthma, and represent a unique target for effective asthma therapy.. nkt cells| epithelial-cells| asthmatic-patients| bronchial-asthma| allergic-asthma| inflammation| mice| hyperresponsiveness| lung| responses.	FEB 18-2008	nkt cells| epithelial-cells| asthmatic-patients| bronchial-asthma| allergic-asthma| inflammation| mice| hyperresponsiveness| lung| responses	Pichavant, M; Goya, S; Meyer, EH; Johnston, RA; Kim, HY; Matangkasombut, P; Zhu, M; Iwakura, Y; Savage, PB; DeKruyff, RH; Shore, SA; Umetsu, DT	Ozone exposure in a mouse model induces airway hyperreactivity that requires the presence of natural killer T cells and IL-17		JOURNAL OF EXPERIMENTAL MEDICINE		NKT CELLS; EPITHELIAL-CELLS; ASTHMATIC-PATIENTS; BRONCHIAL-ASTHMA; ALLERGIC-ASTHMA; INFLAMMATION; MICE; HYPERRESPONSIVENESS; LUNG; RESPONSES	Exposure to ozone, which is a major component of air pollution, induces a form of asthma that occurs in the absence of adaptive immunity. Although ozone-induced asthma is characterized by airway neutrophilia, and not eosinophilia, it is nevertheless associated with airway hyperreactivity (AHR), which is a cardinal feature of asthma. Because AHR induced by allergens requires the presence of natural killer T (NKT) cells, we asked whether ozone-induced AHR had similar requirements. We found that repeated exposure of wild-type (WT) mice to ozone induced severe AHR associated with an increase in airway NKT cells, neutrophils, and macrophages. Surprisingly, NKT cell-deficient (CD1d(-/-) and J alpha 18(-/-)) mice failed to develop ozone-induced AHR. Further, treatment of WT mice with an anti-CD1d mAb blocked NKT cell activation and prevented ozone-induced AHR. Moreover, ozone-induced, but not allergen-induced, AHR was associated with NKT cells producing interleukin (IL)-17, and failed to occur in IL-17(-/-) mice nor in WT mice treated with anti-IL-17 mAb. Thus, ozone exposure induces AHR that requires the presence of NKT cells and IL-17 production. Because NKT cells are required for the development of two very disparate forms of AHR (ozone- and allergen-induced), our results strongly suggest that NKT cells mediate a unifying pathogenic mechanism for several distinct forms of asthma, and represent a unique target for effective asthma therapy.	52	179	2008	9	10.1084/jem.20071507	Immunology; Research & Experimental Medicine
PC20 adenosine 5 '-monophosphate is more closely associated with airway inflammation in asthma than PC20 methacholine. Inhalation of a direct stimulus such as histamine or methacholine is generally used to measure bronchial hyperresponsiveness (BHR). Provocation with adenosine 5'-monophosphate (AMP), an indirect airway challenge, has been suggested to be a better marker of airway inflammation than direct challenges. However, so far little information on this subject is available. The aim of our study was to assess whether the concentration of AMP causing the FEV1 to drop by 20% (PC20) is more closely associated with inflammatory parameters in asthma than PC20 methacholine. In 120 patients with atopic asthma (median FEV1 81% predicted [pred], median age 27 yr), PC20 methacholine and PC20 AMP as well as sputum induction, blood sampling, and measurement of nitric oxide in exhaled air were performed. PC20 methacholine was predominantly predicted by FEV1 %pred (explained variance [ev] = 18%) with the percentage of peripheral blood monocytes being a weak additional independent predictor (total ev = 23%). By contrast, PC20 AMP was predominantly predicted by the percentage of eosinophils in sputum (ev = 25%), while FEV1 %pred was only an additional independent predictor (total ev = 36%). PC20 AMP reflects more closely the extent of airway inflammation due to asthma than PC20 methacholine.. exhaled nitric-oxide| bronchial hyperresponsiveness| allergic rhinitis| induced bronchoconstriction| sputum eosinophils| smooth-muscle| disease| blood| responsiveness| hyperreactivity.	JUN-2001	exhaled nitric-oxide| bronchial hyperresponsiveness| allergic rhinitis| induced bronchoconstriction| sputum eosinophils| smooth-muscle| disease| blood| responsiveness| hyperreactivity	Van dn Berge, M; Meijer, RJ; Kerstjens, HAM; de Reus, DM; Koeter, GH; Kauffman, HF; Postma, DS	PC20 adenosine 5 '-monophosphate is more closely associated with airway inflammation in asthma than PC20 methacholine		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		EXHALED NITRIC-OXIDE; BRONCHIAL HYPERRESPONSIVENESS; ALLERGIC RHINITIS; INDUCED BRONCHOCONSTRICTION; SPUTUM EOSINOPHILS; SMOOTH-MUSCLE; DISEASE; BLOOD; RESPONSIVENESS; HYPERREACTIVITY	Inhalation of a direct stimulus such as histamine or methacholine is generally used to measure bronchial hyperresponsiveness (BHR). Provocation with adenosine 5'-monophosphate (AMP), an indirect airway challenge, has been suggested to be a better marker of airway inflammation than direct challenges. However, so far little information on this subject is available. The aim of our study was to assess whether the concentration of AMP causing the FEV1 to drop by 20% (PC20) is more closely associated with inflammatory parameters in asthma than PC20 methacholine. In 120 patients with atopic asthma (median FEV1 81% predicted [pred], median age 27 yr), PC20 methacholine and PC20 AMP as well as sputum induction, blood sampling, and measurement of nitric oxide in exhaled air were performed. PC20 methacholine was predominantly predicted by FEV1 %pred (explained variance [ev] = 18%) with the percentage of peripheral blood monocytes being a weak additional independent predictor (total ev = 23%). By contrast, PC20 AMP was predominantly predicted by the percentage of eosinophils in sputum (ev = 25%), while FEV1 %pred was only an additional independent predictor (total ev = 36%). PC20 AMP reflects more closely the extent of airway inflammation due to asthma than PC20 methacholine.	33	179	2001	5		General & Internal Medicine; Respiratory System
Transcript imaging of the development of human T helper cells using oligonucleotide arrays. Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation(1) Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes'. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A-subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.. regulatory factor-i| selective expression| immune-responses| p-selectin| interleukin-12| t-helper-1| cytokine| receptor| type-1| lymphocytes.	MAY-2000	regulatory factor-i| selective expression| immune-responses| p-selectin| interleukin-12| t-helper-1| cytokine| receptor| type-1| lymphocytes	Rogge, L; Bianchi, E; Biffi, M; Bono, E; Chang, SYP; Alexander, H; Santini, C; Ferrari, G; Sinigaglia, L; Seiler, M; Neeb, M; Mous, J; Sinigaglia, F; Certa, U	Transcript imaging of the development of human T helper cells using oligonucleotide arrays		NATURE GENETICS		REGULATORY FACTOR-I; SELECTIVE EXPRESSION; IMMUNE-RESPONSES; P-SELECTIN; INTERLEUKIN-12; T-HELPER-1; CYTOKINE; RECEPTOR; TYPE-1; LYMPHOCYTES	Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells at the site of inflammation(1) Understanding the genetic program that controls the functional properties of T helper type 1 (Th1) versus T helper type 2 (Th2) cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene-expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6,000 human genes'. Here we analyse the data sets derived from five independent experiments using statistical algorithms. This approach resulted in the identification of 215 differentially expressed genes, encoding proteins involved in transcriptional regulation, apoptosis, proteolysis, and cell adhesion and migration. A-subset of these genes was further upregulated by exposure of differentiated Th1 cells to interleukin-12 (IL-12), as confirmed by kinetic PCR analysis, indicating that IL-12 modulates the effector functions of Th1 cells in the absence of antigenic stimulation. Functional assays and in vivo expression of selected genes have validated the biological relevance of our study. Our results provide new insight into the transcriptional program controlling the functional diversity of subsets of T helper cells.	29	179	2000	6	10.1038/75671	Genetics & Heredity
The Danger Signal, Extracellular ATP, Is a Sensor for an Airborne Allergen and Triggers IL-33 Release and Innate Th2-Type Responses. The molecular mechanisms underlying the initiation of innate and adaptive proallergic Th2-type responses in the airways are not well understood. IL-33 is a new member of the IL-1 family of molecules that is implicated in Th2-type responses. Airway exposure of naive mice to a common environmental aeroallergen, the fungus Alternaria alternata, induces rapid release of IL-33 into the airway lumen, followed by innate Th2-type responses. Biologically active IL-33 is constitutively stored in the nuclei of human airway epithelial cells. Exposing these epithelial cells to A. alternata releases IL-33 extracellularly in vitro. Allergen exposure also induces acute extracellular accumulation of a danger signal, ATP; autocrine ATP sustains increases in intracellular Ca(2+) concentration and releases IL-33 through activation of P2 purinergic receptors. Pharmacological inhibitors of purinergic receptors or deficiency in the P2Y2 gene abrogate IL-33 release and Th2-type responses in the Alternaria-induced airway inflammation model in naive mice, emphasizing the essential roles for ATP and the P2Y2 receptor. Thus, ATP and purinergic signaling in the respiratory epithelium are critical sensors for airway exposure to airborne allergens, and they may provide novel opportunities to dampen the hypersensitivity response in Th2-type airway diseases such as asthma. The Journal of Immunology, 2011, 186: 4375-4387.. receptor accessory protein| mast-cells| dendritic cells| airway hyperresponsiveness| inflammatory response| adaptive immunity| type-2 immunity| cytokine il-33| nk cells| in-vivo.	APR 1-2011	receptor accessory protein| mast-cells| dendritic cells| airway hyperresponsiveness| inflammatory response| adaptive immunity| type-2 immunity| cytokine il-33| nk cells| in-vivo	Kouzaki, H; Iijima, K; Kobayashi, T; O'Grady, SM; Kita, H	The Danger Signal, Extracellular ATP, Is a Sensor for an Airborne Allergen and Triggers IL-33 Release and Innate Th2-Type Responses		JOURNAL OF IMMUNOLOGY		RECEPTOR ACCESSORY PROTEIN; MAST-CELLS; DENDRITIC CELLS; AIRWAY HYPERRESPONSIVENESS; INFLAMMATORY RESPONSE; ADAPTIVE IMMUNITY; TYPE-2 IMMUNITY; CYTOKINE IL-33; NK CELLS; IN-VIVO	The molecular mechanisms underlying the initiation of innate and adaptive proallergic Th2-type responses in the airways are not well understood. IL-33 is a new member of the IL-1 family of molecules that is implicated in Th2-type responses. Airway exposure of naive mice to a common environmental aeroallergen, the fungus Alternaria alternata, induces rapid release of IL-33 into the airway lumen, followed by innate Th2-type responses. Biologically active IL-33 is constitutively stored in the nuclei of human airway epithelial cells. Exposing these epithelial cells to A. alternata releases IL-33 extracellularly in vitro. Allergen exposure also induces acute extracellular accumulation of a danger signal, ATP; autocrine ATP sustains increases in intracellular Ca(2+) concentration and releases IL-33 through activation of P2 purinergic receptors. Pharmacological inhibitors of purinergic receptors or deficiency in the P2Y2 gene abrogate IL-33 release and Th2-type responses in the Alternaria-induced airway inflammation model in naive mice, emphasizing the essential roles for ATP and the P2Y2 receptor. Thus, ATP and purinergic signaling in the respiratory epithelium are critical sensors for airway exposure to airborne allergens, and they may provide novel opportunities to dampen the hypersensitivity response in Th2-type airway diseases such as asthma. The Journal of Immunology, 2011, 186: 4375-4387.	76	178	2011	13	10.4049/jimmunol.1003020	Immunology
Community violence and asthma morbidity: The inner-city asthma study. Objectives. We examined the association between exposure to violence and asthma among urban children. Methods. We obtained reports from caretakers (n=851) of violence, negative life events, unwanted memories (rumination), caretaker-perceived stress, and caretaker behaviors (keeping children indoors, smoking, and medication adherence). Outcomes included caretaker-reported wheezing, sleep disruption, interference with play because of asthma, and effects on the caretaker (nights caretaker lost sleep because of child's asthma). Results. Increased exposure to violence predicted higher number of symptom days (P=.0008) and more nights that caretakers lost sleep (P=.02) in a graded fashion after control for socioeconomic status, housing deterioration, and negative life events. Control for stress and behaviors partially attenuated this gradient, although these variables had little effect on the association between the highest level of exposure to morbidity, which suggests there are other mechanisms. Conclusions. Mechanisms linking violence and asthma morbidity need to be further explored.. posttraumatic-stress-disorder| cockroach allergen| political violence| urban communities| african-american| life events| children| exposure| population| distress.	APR-2004	posttraumatic-stress-disorder| cockroach allergen| political violence| urban communities| african-american| life events| children| exposure| population| distress	Wright, RJ; Mitchell, H; Visness, CM; Cohen, S; Stout, J; Evans, R; Gold, DR	Community violence and asthma morbidity: The inner-city asthma study		AMERICAN JOURNAL OF PUBLIC HEALTH		POSTTRAUMATIC-STRESS-DISORDER; COCKROACH ALLERGEN; POLITICAL VIOLENCE; URBAN COMMUNITIES; AFRICAN-AMERICAN; LIFE EVENTS; CHILDREN; EXPOSURE; POPULATION; DISTRESS	Objectives. We examined the association between exposure to violence and asthma among urban children. Methods. We obtained reports from caretakers (n=851) of violence, negative life events, unwanted memories (rumination), caretaker-perceived stress, and caretaker behaviors (keeping children indoors, smoking, and medication adherence). Outcomes included caretaker-reported wheezing, sleep disruption, interference with play because of asthma, and effects on the caretaker (nights caretaker lost sleep because of child's asthma). Results. Increased exposure to violence predicted higher number of symptom days (P=.0008) and more nights that caretakers lost sleep (P=.02) in a graded fashion after control for socioeconomic status, housing deterioration, and negative life events. Control for stress and behaviors partially attenuated this gradient, although these variables had little effect on the association between the highest level of exposure to morbidity, which suggests there are other mechanisms. Conclusions. Mechanisms linking violence and asthma morbidity need to be further explored.	59	178	2004	8	10.2105/AJPH.94.4.625	Public, Environmental & Occupational Health
Diagnosing and Managing Common Food Allergies A Systematic Review. Context There is heightened interest in food allergies but no clear consensus exists regarding the prevalence or most effective diagnostic and management approaches to food allergies. Objective To perform a systematic review of the available evidence on the prevalence, diagnosis, management, and prevention of food allergies. Data Sources Electronic searches of PubMed, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials. Searches were limited to English-language articles indexed between January 1988 and September 2009. Study Selection Diagnostic tests were included if they had a prospective, defined study population, used food challenge as a criterion standard, and reported sufficient data to calculate sensitivity and specificity. Systematic reviews and randomized controlled trials (RCTs) for management and prevention outcomes were also used. For foods where anaphylaxis is common, cohort studies with a sample size of more than 100 participants were included. Data Extraction Two investigators independently reviewed all titles and abstracts to identify potentially relevant articles and resolved discrepancies by repeated review and discussion. Quality of systematic reviews and meta-analyses was assessed using the AMSTAR criteria, the quality of diagnostic studies using the QUADAS criteria most relevant to food allergy, and the quality of RCTs using the Jadad criteria. Data Synthesis A total of 12 378 citations were identified and 72 citations were included. Food allergy affects more than 1% to 2% but less than 10% of the population. It is unclear if the prevalence of food allergies is increasing. Summary receiver operating characteristic curves comparing skin prick tests (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.81-0.93) and serum food-specific IgE (AUC, 0.84; 95% CI, 0.78-0.91) to food challenge showed no statistical superiority for either test. Elimination diets are the mainstay of therapy but have been rarely studied. Immunotherapy is promising but data are insufficient to recommend use. In high-risk infants, hydrolyzed formulas may prevent cow's milk allergy but standardized definitions of high risk and hydrolyzed formula do not exist. Conclusion The evidence for the prevalence and management of food allergy is greatly limited by a lack of uniformity for criteria for making a diagnosis. JAMA. 2010; 303(18): 1848-1856. cows milk allergy| placebo-controlled trial| high-risk infants| atopy patch test| breast-fed infants| randomized controlled-trial| brief neonatal exposure| double-blind trial| skin-prick tests| 1st 2 years.	MAY 12-2010	cows milk allergy| placebo-controlled trial| high-risk infants| atopy patch test| breast-fed infants| randomized controlled-trial| brief neonatal exposure| double-blind trial| skin-prick tests| 1st 2 years	Chafen, JJS; Newberry, SJ; Riedl, MA; Bravata, DM; Maglione, M; Suttorp, MJ; Sundaram, V; Paige, NM; Towfigh, A; Hulley, BJ; Shekelle, PG	Diagnosing and Managing Common Food Allergies A Systematic Review		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		COWS MILK ALLERGY; PLACEBO-CONTROLLED TRIAL; HIGH-RISK INFANTS; ATOPY PATCH TEST; BREAST-FED INFANTS; RANDOMIZED CONTROLLED-TRIAL; BRIEF NEONATAL EXPOSURE; DOUBLE-BLIND TRIAL; SKIN-PRICK TESTS; 1ST 2 YEARS	Context There is heightened interest in food allergies but no clear consensus exists regarding the prevalence or most effective diagnostic and management approaches to food allergies. Objective To perform a systematic review of the available evidence on the prevalence, diagnosis, management, and prevention of food allergies. Data Sources Electronic searches of PubMed, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effects, and Cochrane Central Register of Controlled Trials. Searches were limited to English-language articles indexed between January 1988 and September 2009. Study Selection Diagnostic tests were included if they had a prospective, defined study population, used food challenge as a criterion standard, and reported sufficient data to calculate sensitivity and specificity. Systematic reviews and randomized controlled trials (RCTs) for management and prevention outcomes were also used. For foods where anaphylaxis is common, cohort studies with a sample size of more than 100 participants were included. Data Extraction Two investigators independently reviewed all titles and abstracts to identify potentially relevant articles and resolved discrepancies by repeated review and discussion. Quality of systematic reviews and meta-analyses was assessed using the AMSTAR criteria, the quality of diagnostic studies using the QUADAS criteria most relevant to food allergy, and the quality of RCTs using the Jadad criteria. Data Synthesis A total of 12 378 citations were identified and 72 citations were included. Food allergy affects more than 1% to 2% but less than 10% of the population. It is unclear if the prevalence of food allergies is increasing. Summary receiver operating characteristic curves comparing skin prick tests (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.81-0.93) and serum food-specific IgE (AUC, 0.84; 95% CI, 0.78-0.91) to food challenge showed no statistical superiority for either test. Elimination diets are the mainstay of therapy but have been rarely studied. Immunotherapy is promising but data are insufficient to recommend use. In high-risk infants, hydrolyzed formulas may prevent cow's milk allergy but standardized definitions of high risk and hydrolyzed formula do not exist. Conclusion The evidence for the prevalence and management of food allergy is greatly limited by a lack of uniformity for criteria for making a diagnosis. JAMA. 2010; 303(18): 1848-1856	113	177	2010	9	10.1001/jama.2010.582	General & Internal Medicine
Allergens are distributed into few protein families and possess a restricted number of biochemical functions. Background: Existing allergen databases classify their entries by source and route of exposure, thus lacking an evolutionary, structural, and functional classification of allergens. Objective: We sought to build AllFam, a database of allergen families, and use it to extract common structural and functional properties of allergens. Methods: Allergen data from the Allergome database and protein family definitions from the Pfam database were merged into AllFam, a database that is freely accessible on the Internet at: http://www.meduniwien.ac.at/allergens/allfam/. A structural classification of allergens was established by matching Pfam families with families from the Structural Classification of Proteins database. Biochemical functions of allergens were extracted from the Gene Ontology Annotation database. Results: Seven hundred seven allergens were classified by sequence into 134 AllFam families containing 184 Pfam domains (2% of 9318 Pfam families). A random set of 707 sequences with the same taxonomic distribution contained a significantly higher number of different Pfam domains (479 +/- 17). Classifying allergens by structure revealed that 5% of 3012 Structural Classification of Proteins families contained allergens. The biochemical functions of allergens most frequently found were limited to hydrolysis of proteins, polysaccharides, and lipids; binding of metal ions and lipids; storage; and cytoskeleton association. Conclusion: The small number of protein families that contain allergens and the narrow functional distribution of most allergens confirm the existence of yet unknown factors that render proteins allergenic.. allergens| protein families| allergen structures| allergen databases|plant food allergens| structural biology| cross-reactivity| pollen allergens| sequence| homologs| tools.	APR-2008	allergens| protein families| allergen structures| allergen databases|plant food allergens| structural biology| cross-reactivity| pollen allergens| sequence| homologs| tools	Radauer, C; Bublin, M; Wagner, S; Mari, A; Breiteneder, H	Allergens are distributed into few protein families and possess a restricted number of biochemical functions		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergens; protein families; allergen structures; allergen databases	PLANT FOOD ALLERGENS; STRUCTURAL BIOLOGY; CROSS-REACTIVITY; POLLEN ALLERGENS; SEQUENCE; HOMOLOGS; TOOLS	Background: Existing allergen databases classify their entries by source and route of exposure, thus lacking an evolutionary, structural, and functional classification of allergens. Objective: We sought to build AllFam, a database of allergen families, and use it to extract common structural and functional properties of allergens. Methods: Allergen data from the Allergome database and protein family definitions from the Pfam database were merged into AllFam, a database that is freely accessible on the Internet at: http://www.meduniwien.ac.at/allergens/allfam/. A structural classification of allergens was established by matching Pfam families with families from the Structural Classification of Proteins database. Biochemical functions of allergens were extracted from the Gene Ontology Annotation database. Results: Seven hundred seven allergens were classified by sequence into 134 AllFam families containing 184 Pfam domains (2% of 9318 Pfam families). A random set of 707 sequences with the same taxonomic distribution contained a significantly higher number of different Pfam domains (479 +/- 17). Classifying allergens by structure revealed that 5% of 3012 Structural Classification of Proteins families contained allergens. The biochemical functions of allergens most frequently found were limited to hydrolysis of proteins, polysaccharides, and lipids; binding of metal ions and lipids; storage; and cytoskeleton association. Conclusion: The small number of protein families that contain allergens and the narrow functional distribution of most allergens confirm the existence of yet unknown factors that render proteins allergenic.	29	177	2008	6	10.1016/j.jaci.2008.01.025	Allergy; Immunology
Atopic sensitization and the international variation of asthma symptom prevalence in children. Rationale: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further. Objectives: To Investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma. Methods: Cross-sectional studies of random samples of 8- to 12-yearold children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 311,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI). Measurements and Main Results: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient p = 0.50, P = 0.006, and p = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (p = 0.47, P = 0.01). Conclusions: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.. wheeze| isaac phase two| ige| population attributable risk| gross national income per capita|childhood isaac| respiratory symptoms| bronchial hyperresponsiveness| estonian children| allergen exposure| different pattern| school-children| semirural area| risk-factors| wheeze.	SEP 15-2007	wheeze| isaac phase two| ige| population attributable risk| gross national income per capita|childhood isaac| respiratory symptoms| bronchial hyperresponsiveness| estonian children| allergen exposure| different pattern| school-children| semirural area| risk-factors| wheeze	Weinmayr, G; Weiland, SK; Bjorksten, B; Brunekreef, B; Buchele, G; Cookson, WOC; Garcia-Marcos, L; Gotua, M; Gratziou, C; van Hage, M; von Mutius, E; Riikjarv, MA; Rzehak, P; Stein, RT; Strachan, DP; Tsanakas, J; Wickens, K; Wong, GW	Atopic sensitization and the international variation of asthma symptom prevalence in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	wheeze; ISAAC Phase Two; IgE; population attributable risk; gross national income per capita	CHILDHOOD ISAAC; RESPIRATORY SYMPTOMS; BRONCHIAL HYPERRESPONSIVENESS; ESTONIAN CHILDREN; ALLERGEN EXPOSURE; DIFFERENT PATTERN; SCHOOL-CHILDREN; SEMIRURAL AREA; RISK-FACTORS; WHEEZE	Rationale: Atopic sensitization has long been known to be related to asthma in children, but its role in determining asthma prevalence remains to be elucidated further. Objectives: To Investigate the role of atopic sensitization in the large international variation in the prevalence of childhood asthma. Methods: Cross-sectional studies of random samples of 8- to 12-yearold children (n = 1,000 per center) were performed according to the standardized methodology of Phase Two of the International Study of Asthma and Allergy in Childhood (ISAAC). Thirty study centers in 22 countries worldwide participated and reflect a wide range of living conditions, from rural Africa to urban Europe. Data were collected by parental questionnaires (n = 54,439), skin prick tests (n = 311,759), and measurements of allergen-specific IgE levels in serum (n = 8,951). Economic development was assessed by gross national income per capita (GNI). Measurements and Main Results: The prevalence of current wheeze (i.e., during the past year) ranged from 0.8% in Pichincha (Ecuador) to 25.6% in Uruguaiana (Brazil). The fraction of current wheeze attributable to atopic sensitization ranged from 0% in Ankara (Turkey) to 93.8% in Guangzhou (China). There were no correlations between prevalence rates of current wheeze and atopic sensitization, and only weak correlations of both with GNI. However, the fractions and prevalence rates of wheeze attributable to skin test reactivity correlated strongly with GNI (Spearman rank-order coefficient p = 0.50, P = 0.006, and p = 0.74, P < 0.0001, respectively). In addition, the strength of the association between current wheeze and skin test reactivity, assessed by odds ratios, increased with GNI (p = 0.47, P = 0.01). Conclusions: The link between atopic sensitization and asthma symptoms in children differs strongly between populations and increases with economic development.	50	177	2007	10	10.1164/rccm.200607-994OC	General & Internal Medicine; Respiratory System
How exposure to environmental tobacco smoke, outdoor air pollutants, and increased pollen burdens influences the incidence of asthma. Asthma is a multifactorial airway disease that arises from a relatively common genetic background interphased with exposures to allergens and airborne irritants. The rapid rise in asthma over the past three decades in Western societies has been attributed to numerous diverse factors, including increased awareness of the disease, altered lifestyle and activity patterns, and ill-defined changes in environmental exposures. It is well accepted that persons with asthma are more sensitive than persons without asthma to air pollutants such as cigarette smoke, traffic emissions, and photochemical smog components. It has also been demonstrated that exposure to a mix of allergens and irritants can at times promote the development phase (induction) of the disease. Experimental evidence suggests that complex organic molecules from diesel exhaust may act as allergic adjuvants through the production of oxidative stress in airway cells. It also seems that climate change is increasing the abundance of aeroallergens Such as pollen, which may result in greater incidence or severity of allergic diseases. In this review we illustrate how environmental tobacco smoke, outdoor air pollution, and climate change may act as environmental risk factors for the development of asthma and provide mechanistic explanations for how some of these effects can occur.. air pollution| asthma| cigarette smoke| climate change| diesel exhaust| environment| inflammation| mechanisms| ozone| particulate matter| pollen|exhaust particle chemicals| lower respiratory illness| diesel exhaust| parental smoking| oxidative stress| atmospheric co2| elevated co2| carbon-dioxide| climate-change| health.	APR-2006	air pollution| asthma| cigarette smoke| climate change| diesel exhaust| environment| inflammation| mechanisms| ozone| particulate matter| pollen|exhaust particle chemicals| lower respiratory illness| diesel exhaust| parental smoking| oxidative stress| atmospheric co2| elevated co2| carbon-dioxide| climate-change| health	Gilmour, M; Jaakkola, MS; London, SJ; Nel, AE; Rogers, CA	How exposure to environmental tobacco smoke, outdoor air pollutants, and increased pollen burdens influences the incidence of asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma; cigarette smoke; climate change; diesel exhaust; environment; inflammation; mechanisms; ozone; particulate matter; pollen	EXHAUST PARTICLE CHEMICALS; LOWER RESPIRATORY ILLNESS; DIESEL EXHAUST; PARENTAL SMOKING; OXIDATIVE STRESS; ATMOSPHERIC CO2; ELEVATED CO2; CARBON-DIOXIDE; CLIMATE-CHANGE; HEALTH	Asthma is a multifactorial airway disease that arises from a relatively common genetic background interphased with exposures to allergens and airborne irritants. The rapid rise in asthma over the past three decades in Western societies has been attributed to numerous diverse factors, including increased awareness of the disease, altered lifestyle and activity patterns, and ill-defined changes in environmental exposures. It is well accepted that persons with asthma are more sensitive than persons without asthma to air pollutants such as cigarette smoke, traffic emissions, and photochemical smog components. It has also been demonstrated that exposure to a mix of allergens and irritants can at times promote the development phase (induction) of the disease. Experimental evidence suggests that complex organic molecules from diesel exhaust may act as allergic adjuvants through the production of oxidative stress in airway cells. It also seems that climate change is increasing the abundance of aeroallergens Such as pollen, which may result in greater incidence or severity of allergic diseases. In this review we illustrate how environmental tobacco smoke, outdoor air pollution, and climate change may act as environmental risk factors for the development of asthma and provide mechanistic explanations for how some of these effects can occur.	77	177	2006	7	10.1289/ehp.8380	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma. Background: The effectiveness of avoidance of house-dust-mite allergen (Dermatophagoides pteronyssinus 1 [Der p1]) in the management of asthma is uncertain. Methods: We conducted a double-blind, randomized, placebo-controlled study of allergen-impermeable bed covers involving 1122 adults with asthma. The primary outcomes were the mean morning peak expiratory flow rate over a four-week period during the run-in phase and at six months and the proportion of patients who discontinued inhaled corticosteroid therapy as part of a phased-reduction program during months 7 through 12. Der p1 was measured in mattress dust in a 10 percent random subsample of homes at entry and at 6 and 12 months. Results: The prevalence of sensitivity to dust-mite allergen was 65.4 percent in the group supplied with allergen-impermeable bed covers (active-intervention group) and 65.1 percent in the control group supplied with non-impermeable bed covers. The concentration of Der p1 in mattress dust was significantly lower in the active-intervention group at 6 months (geometric mean, 0.58 mug per gram vs. 1.71 mug per gram in the control group; P=0.01) but not at 12 months (1.05 mug per gram vs. 1.64 mug per gram; P=0.74). The mean morning peak expiratory flow rate improved significantly in both groups (from 410.7 to 419.1 liters per minute in the active-intervention group, P<0.001 for the change; and from 417.8 to 427.4 liters per minute in the control group, P<0.001 for the change). After adjustment for base-line differences (by analysis of covariance), there was no significant difference between the groups in the peak expiratory flow rate at six months (difference in means, active-intervention group vs. control group, -1.6 liters per minute [95 percent confidence interval, -5.9 to 2.7] among all patients [P=0.46] and -1.5 liters per minute [95 percent confidence interval, -6.9 to 3.9] among mite-sensitive patients [P=0.59]). There was no significant difference between the groups in the proportion in whom complete cessation of inhaled corticosteroid therapy was achieved (17.4 percent in the active-intervention group and 17.1 percent in the control group) or in the mean reduction in steroid dose, either among all patients or among mite-sensitive patients. Conclusions: Allergen-impermeable covers, as a single intervention for the avoidance of exposure to dust-mite allergen, seem clinically ineffective in adults with asthma.. inhaled steroids| controlled trial| occupational asthma| indoor allergens| avoidance| children| encasement| reduction| mattress.	JUL 17-2003	inhaled steroids| controlled trial| occupational asthma| indoor allergens| avoidance| children| encasement| reduction| mattress	Woodcock, A; Forster, L; Matthews, E; Martin, J; Letley, L; Vickers, M; Britton, J; Strachan, D; Howarth, P; Altmann, D; Frost, C; Custovic, A	Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma		NEW ENGLAND JOURNAL OF MEDICINE		INHALED STEROIDS; CONTROLLED TRIAL; OCCUPATIONAL ASTHMA; INDOOR ALLERGENS; AVOIDANCE; CHILDREN; ENCASEMENT; REDUCTION; MATTRESS	Background: The effectiveness of avoidance of house-dust-mite allergen (Dermatophagoides pteronyssinus 1 [Der p1]) in the management of asthma is uncertain. Methods: We conducted a double-blind, randomized, placebo-controlled study of allergen-impermeable bed covers involving 1122 adults with asthma. The primary outcomes were the mean morning peak expiratory flow rate over a four-week period during the run-in phase and at six months and the proportion of patients who discontinued inhaled corticosteroid therapy as part of a phased-reduction program during months 7 through 12. Der p1 was measured in mattress dust in a 10 percent random subsample of homes at entry and at 6 and 12 months. Results: The prevalence of sensitivity to dust-mite allergen was 65.4 percent in the group supplied with allergen-impermeable bed covers (active-intervention group) and 65.1 percent in the control group supplied with non-impermeable bed covers. The concentration of Der p1 in mattress dust was significantly lower in the active-intervention group at 6 months (geometric mean, 0.58 mug per gram vs. 1.71 mug per gram in the control group; P=0.01) but not at 12 months (1.05 mug per gram vs. 1.64 mug per gram; P=0.74). The mean morning peak expiratory flow rate improved significantly in both groups (from 410.7 to 419.1 liters per minute in the active-intervention group, P<0.001 for the change; and from 417.8 to 427.4 liters per minute in the control group, P<0.001 for the change). After adjustment for base-line differences (by analysis of covariance), there was no significant difference between the groups in the peak expiratory flow rate at six months (difference in means, active-intervention group vs. control group, -1.6 liters per minute [95 percent confidence interval, -5.9 to 2.7] among all patients [P=0.46] and -1.5 liters per minute [95 percent confidence interval, -6.9 to 3.9] among mite-sensitive patients [P=0.59]). There was no significant difference between the groups in the proportion in whom complete cessation of inhaled corticosteroid therapy was achieved (17.4 percent in the active-intervention group and 17.1 percent in the control group) or in the mean reduction in steroid dose, either among all patients or among mite-sensitive patients. Conclusions: Allergen-impermeable covers, as a single intervention for the avoidance of exposure to dust-mite allergen, seem clinically ineffective in adults with asthma.	25	177	2003	12	10.1056/NEJMoa023175	General & Internal Medicine
Effect of cat and dog ownership on sensitization and development of asthma among preteenage children. An inverse relationship has been proposed between exposure to high quantities of cat allergen at home and both asthma and cat allergy. First- and second-grade children from Lule (a) over circle, Kiruna, and Pite (a) over circle, Sweden participated in an asthma questionnaire study (n = 3,431) and incidence was evaluated over the next 3 years. Skin testing was performed on the children in Lule (a) over circle and Kiruna (n = 2,149). The strongest risk factor for incident cases of asthma was Type 1 allergy (relative risk [RR], 4.9 [2.9-8.4]), followed by a family history of asthma (RR, 2.83 [1.8-4.5]). Living with a cat was inversely related both to having a positive skin test to cat (1111, 0.62 [0.47-0.83]) and incidence of physician-diagnosed asthma (1111, 0.49 [0.28-0.83]). This effect on incident asthma was most pronounced among the children with a family history of asthma (RR, 0.25 [0.08-0.80]). The evidence also suggests that many of the children exposed to cats at home can develop an immune response that does not include immunoglobulin E. Weaker protective trends were seen with dog ownership. The traditional thinking that not owning cats can provide protection against developing allergy and asthma among those with a family history of allergy needs to be re-evaluated. In a community where cat sensitization was strongly associated with asthma, owning a cat was protective against both prevalent and incident asthma.. allergy| asthma| cat| dog| tolerance|house-dust mite| inner-city children| cockroach allergen| northern sweden| risk-factors| exposure| morbidity| schools| homes| ige.	SEP 1-2002	allergy| asthma| cat| dog| tolerance|house-dust mite| inner-city children| cockroach allergen| northern sweden| risk-factors| exposure| morbidity| schools| homes| ige	Perzanowski, MS; Ronmark, E; Platts-Mills, TAE; Lundback, B	Effect of cat and dog ownership on sensitization and development of asthma among preteenage children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	allergy; asthma; cat; dog; tolerance	HOUSE-DUST MITE; INNER-CITY CHILDREN; COCKROACH ALLERGEN; NORTHERN SWEDEN; RISK-FACTORS; EXPOSURE; MORBIDITY; SCHOOLS; HOMES; IGE	An inverse relationship has been proposed between exposure to high quantities of cat allergen at home and both asthma and cat allergy. First- and second-grade children from Lule (a) over circle, Kiruna, and Pite (a) over circle, Sweden participated in an asthma questionnaire study (n = 3,431) and incidence was evaluated over the next 3 years. Skin testing was performed on the children in Lule (a) over circle and Kiruna (n = 2,149). The strongest risk factor for incident cases of asthma was Type 1 allergy (relative risk [RR], 4.9 [2.9-8.4]), followed by a family history of asthma (RR, 2.83 [1.8-4.5]). Living with a cat was inversely related both to having a positive skin test to cat (1111, 0.62 [0.47-0.83]) and incidence of physician-diagnosed asthma (1111, 0.49 [0.28-0.83]). This effect on incident asthma was most pronounced among the children with a family history of asthma (RR, 0.25 [0.08-0.80]). The evidence also suggests that many of the children exposed to cats at home can develop an immune response that does not include immunoglobulin E. Weaker protective trends were seen with dog ownership. The traditional thinking that not owning cats can provide protection against developing allergy and asthma among those with a family history of allergy needs to be re-evaluated. In a community where cat sensitization was strongly associated with asthma, owning a cat was protective against both prevalent and incident asthma.	36	177	2002	7	10.1164/rccm.2201035	General & Internal Medicine; Respiratory System
Parental stress as a predictor of wheezing in infancy - A prospective birth-cohort study. The role of stress in the pathogenesis of childhood wheeze remains controversial. Caretaker stress might influence wheeze through stress-induced behavioral changes In caregivers (e.g., smoking, breast-feeding) or biologic processes impacting infant development (e.g., immune response, susceptibility to lower respiratory infections). The influence of caregiver stress on wheeze in infancy was studied in a genetically predisposed prospective birth-cohort (n = 496). Caregiver-perceived stress and wheeze in the children were ascertained bimonthly from the first 2 to 3 mo of life. Greater levels of caregiver-perceived stress at 2 to 3 mo was associated with increased risk of subsequent repeated wheeze among the children during the first 14 mo of life (RR, 1.6; 95% Cl, 1.3 to 1.9). Caregiver-perceived stress remained significant (RR, 1.4; 9S% Cl, 1.1 to 1.9) when controlling for factors potentially associated with both stress and wheeze (parental asthma, socioeconomic status, birth weight, and race/ethnicity) as well as mediators through which stress might influence wheeze (maternal smoking, breast-feeding, indoor allergen exposures, and lower respiratory infections). Furthermore, caregiver stress prospectively predicted wheeze In the infants, whereas wheeze In the children did not predict subsequent caregiver stress. The effect of caregiver stress on early childhood wheeze was independent of caregiver smoking and breast-feeding behaviors, as well as allergen exposure, birth weight, and lower respiratory Infections. These findings suggest a more direct mechanism may be operating between stress and wheeze In early childhood. Stress may contribute significantly to the population burden of preventable childhood respiratory illness.. caregiver stress| wheeze| infancy| birth cohort|psychological stress| behavioral-response| respiratory illness| allergen levels| early-childhood| immune-system| common cold| 1st year| asthma| life.	FEB 1-2002	caregiver stress| wheeze| infancy| birth cohort|psychological stress| behavioral-response| respiratory illness| allergen levels| early-childhood| immune-system| common cold| 1st year| asthma| life	Wright, RJ; Cohen, S; Carey, V; Weiss, ST; Gold, DR	Parental stress as a predictor of wheezing in infancy - A prospective birth-cohort study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	caregiver stress; wheeze; infancy; birth cohort	PSYCHOLOGICAL STRESS; BEHAVIORAL-RESPONSE; RESPIRATORY ILLNESS; ALLERGEN LEVELS; EARLY-CHILDHOOD; IMMUNE-SYSTEM; COMMON COLD; 1ST YEAR; ASTHMA; LIFE	The role of stress in the pathogenesis of childhood wheeze remains controversial. Caretaker stress might influence wheeze through stress-induced behavioral changes In caregivers (e.g., smoking, breast-feeding) or biologic processes impacting infant development (e.g., immune response, susceptibility to lower respiratory infections). The influence of caregiver stress on wheeze in infancy was studied in a genetically predisposed prospective birth-cohort (n = 496). Caregiver-perceived stress and wheeze in the children were ascertained bimonthly from the first 2 to 3 mo of life. Greater levels of caregiver-perceived stress at 2 to 3 mo was associated with increased risk of subsequent repeated wheeze among the children during the first 14 mo of life (RR, 1.6; 95% Cl, 1.3 to 1.9). Caregiver-perceived stress remained significant (RR, 1.4; 9S% Cl, 1.1 to 1.9) when controlling for factors potentially associated with both stress and wheeze (parental asthma, socioeconomic status, birth weight, and race/ethnicity) as well as mediators through which stress might influence wheeze (maternal smoking, breast-feeding, indoor allergen exposures, and lower respiratory infections). Furthermore, caregiver stress prospectively predicted wheeze In the infants, whereas wheeze In the children did not predict subsequent caregiver stress. The effect of caregiver stress on early childhood wheeze was independent of caregiver smoking and breast-feeding behaviors, as well as allergen exposure, birth weight, and lower respiratory Infections. These findings suggest a more direct mechanism may be operating between stress and wheeze In early childhood. Stress may contribute significantly to the population burden of preventable childhood respiratory illness.	55	177	2002	8		General & Internal Medicine; Respiratory System
Airborne concentrations of PM2.5 and diesel exhaust particles on Harlem sidewalks: A community-based pilot study. Residents of the dense urban core neighborhoods of New York City (NYC) have expressed increasing concern about the potential human health impacts of diesel vehicle emissions. We measured concentrations of particulate matter less than or equal to 2.5 mu m in aerodynamic diameter (PM2.5) and diesel exhaust particles (DEP) on sidewalks in Harlem, NYC, and tested whether spatial variations in concentrations were related to local diesel traffic density. Eight-hour (1000-1800 hr) air samples for PM2.5 and elemental carbon (EC) were collected for 5 days in July 1996 on sidewalks adjacent to four geographically distinct Harlem intersections. Samples were taken using portable monitors worn by study staff. Simultaneous traffic counts for diesel trucks, buses, cars, and pedestrians were carried out at each intersection on greater than or equal to 2 of the 5 sampling days. Eight-hour diesel vehicle counts ranged from 61 to 2,467 across the four sires. Mean concentrations of PM2.5 exhibited only modest site-to-site variation (37-47 mu g/m(3)), reflecting the importance of broader regional sources of PM2.5. In contrast, EC concentrations varied 4-fold across sites (from 1.5 to 6 mu g/m(3)), and were associated with bus and truck counts on adjacent streets and, at one site, with the presence of a bus depot. A high correlation (r = 0.95) was observed between EC concentrations measured analytically and a blackness measurement based on PM2.5 filter reflectance, suggesting the utility of the tatter as a surrogate measure of DEP in future community-based studies. These results show that local diesel sources in Harlem create spatial variations in sidewalk concentrations of DEP. The study also demonstrates the feasibility of a new paradigm for community-based research involving full and active partnership between academic scientists and community-based organizations.. diesel exhaust| harlem| outdoor air pollution| pm2.5 urban|particulate air-pollution| respiratory hospital admissions| elemental carbon| epithelial-cells| asthma| children| mortality| exposure| aerosol| hydrocarbons.	MAR-2000	diesel exhaust| harlem| outdoor air pollution| pm2.5 urban|particulate air-pollution| respiratory hospital admissions| elemental carbon| epithelial-cells| asthma| children| mortality| exposure| aerosol| hydrocarbons	Kinney, PL; Aggarwal, M; Northridge, ME; Janssen, NAH; Shepard, P	Airborne concentrations of PM2.5 and diesel exhaust particles on Harlem sidewalks: A community-based pilot study		ENVIRONMENTAL HEALTH PERSPECTIVES	diesel exhaust; Harlem; outdoor air pollution; PM2.5 urban	PARTICULATE AIR-POLLUTION; RESPIRATORY HOSPITAL ADMISSIONS; ELEMENTAL CARBON; EPITHELIAL-CELLS; ASTHMA; CHILDREN; MORTALITY; EXPOSURE; AEROSOL; HYDROCARBONS	Residents of the dense urban core neighborhoods of New York City (NYC) have expressed increasing concern about the potential human health impacts of diesel vehicle emissions. We measured concentrations of particulate matter less than or equal to 2.5 mu m in aerodynamic diameter (PM2.5) and diesel exhaust particles (DEP) on sidewalks in Harlem, NYC, and tested whether spatial variations in concentrations were related to local diesel traffic density. Eight-hour (1000-1800 hr) air samples for PM2.5 and elemental carbon (EC) were collected for 5 days in July 1996 on sidewalks adjacent to four geographically distinct Harlem intersections. Samples were taken using portable monitors worn by study staff. Simultaneous traffic counts for diesel trucks, buses, cars, and pedestrians were carried out at each intersection on greater than or equal to 2 of the 5 sampling days. Eight-hour diesel vehicle counts ranged from 61 to 2,467 across the four sires. Mean concentrations of PM2.5 exhibited only modest site-to-site variation (37-47 mu g/m(3)), reflecting the importance of broader regional sources of PM2.5. In contrast, EC concentrations varied 4-fold across sites (from 1.5 to 6 mu g/m(3)), and were associated with bus and truck counts on adjacent streets and, at one site, with the presence of a bus depot. A high correlation (r = 0.95) was observed between EC concentrations measured analytically and a blackness measurement based on PM2.5 filter reflectance, suggesting the utility of the tatter as a surrogate measure of DEP in future community-based studies. These results show that local diesel sources in Harlem create spatial variations in sidewalk concentrations of DEP. The study also demonstrates the feasibility of a new paradigm for community-based research involving full and active partnership between academic scientists and community-based organizations.	36	177	2000	6	10.2307/3454436	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
IL-17A produced by alpha beta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction. Emerging evidence suggests that the T helper 17 (T(H)17) subset of alpha beta T cells contributes to the development of allergic asthma. In this study, we found that mice lacking the alpha v beta 8 integrin on dendritic cells did not generate T(H)17 cells in the lung and were protected from airway hyper-responsiveness in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without any obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin-17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear factor kappa light-chain enhancer of activated B cells (NF-kappa B)-ras homolog gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling cascade. Mice lacking integrin alpha v beta 8 on dendritic cells showed impaired activation of this pathway after ovalbumin sensitization and challenge, and the diminished contraction of the tracheal rings in these mice was reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells contributes to allergen-induced airway hyper-responsiveness through direct effects on airway smooth muscle.. growth-factor-beta| ror-gamma-t| allergic-asthma| gene polymorphisms| t(h)17 cells| rho-kinase| receptor| inflammation| interleukin-17| association.	APR-2012	growth-factor-beta| ror-gamma-t| allergic-asthma| gene polymorphisms| t(h)17 cells| rho-kinase| receptor| inflammation| interleukin-17| association	Kudo, M; Melton, AC; Chen, C; Engler, MB; Huang, KE; Ren, X; Wang, YL; Bernstein, X; Li, JT; Atabai, K; Huang, XZ; Sheppard, D	IL-17A produced by alpha beta T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction		NATURE MEDICINE		GROWTH-FACTOR-BETA; ROR-GAMMA-T; ALLERGIC-ASTHMA; GENE POLYMORPHISMS; T(H)17 CELLS; RHO-KINASE; RECEPTOR; INFLAMMATION; INTERLEUKIN-17; ASSOCIATION	Emerging evidence suggests that the T helper 17 (T(H)17) subset of alpha beta T cells contributes to the development of allergic asthma. In this study, we found that mice lacking the alpha v beta 8 integrin on dendritic cells did not generate T(H)17 cells in the lung and were protected from airway hyper-responsiveness in response to house dust mite and ovalbumin sensitization and challenge. Because loss of T(H)17 cells inhibited airway narrowing without any obvious effects on airway inflammation or epithelial morphology, we examined the direct effects of T(H)17 cytokines on mouse and human airway smooth muscle function. Interleukin-17A (IL-17A), but not IL-17F or IL-22, enhanced contractile force generation of airway smooth muscle through an IL-17 receptor A (IL-17RA)-IL-17RC, nuclear factor kappa light-chain enhancer of activated B cells (NF-kappa B)-ras homolog gene family, member A (RhoA)-Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling cascade. Mice lacking integrin alpha v beta 8 on dendritic cells showed impaired activation of this pathway after ovalbumin sensitization and challenge, and the diminished contraction of the tracheal rings in these mice was reversed by IL-17A. These data indicate that the IL-17A produced by T(H)17 cells contributes to allergen-induced airway hyper-responsiveness through direct effects on airway smooth muscle.	55	176	2012	8	10.1038/nm.2684	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma. Background: A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma. Methods: We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life. Results: Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5 x 10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8 x 10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure). Conclusions: This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.. environmental tobacco-smoke| childhood asthma| bronchial hyperresponsiveness| ormdl3 expression| childrens health| lung-function| gene| association| life| polymorphism.	NOV 6-2008	environmental tobacco-smoke| childhood asthma| bronchial hyperresponsiveness| ormdl3 expression| childrens health| lung-function| gene| association| life| polymorphism	Bouzigon, E; Corda, E; Aschard, H; Dizier, MH; Boland, A; Bousquet, J; Chateigner, N; Gormand, F; Just, J; Le Moual, N; Scheinmann, P; Siroux, V; Vervloet, D; Zelenika, D; Pin, I; Kauffmann, F; Lathrop, M; Demenais, F	Effect of 17q21 Variants and Smoking Exposure in Early-Onset Asthma		NEW ENGLAND JOURNAL OF MEDICINE		ENVIRONMENTAL TOBACCO-SMOKE; CHILDHOOD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS; ORMDL3 EXPRESSION; CHILDRENS HEALTH; LUNG-FUNCTION; GENE; ASSOCIATION; LIFE; POLYMORPHISM	Background: A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma. Methods: We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life. Results: Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5 x 10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8 x 10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure). Conclusions: This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.	38	176	2008	10	10.1056/NEJMoa0806604	General & Internal Medicine
The sentinel role of the airway epithelium in asthma pathogenesis. The adoption of the concept that asthma is primarily a disease most frequently associated with elaboration of T-helper 2 (Th2)-type inflammation has led to the widely held concept that its origins, exacerbation, and persistence are allergen driven. Taking aside the asthma that is expressed in non-allergic individuals leaves the great proportion of asthma that is associated with allergy (or atopy) and that often has its onset in early childhood. Evidence is presented that asthma is primarily an epithelial disorder and that its origin as well as its clinical manifestations have more to do with altered epithelial physical and functional barrier properties than being purely linked to allergic pathways. In genetically susceptible individuals, impaired epithelial barrier function renders the airways vulnerable to early life virus infection, and this in turn provides the stimulus to prime immature dendritic cells toward directing a Th2 response and local allergen sensitization. Continued epithelial susceptibility to environmental insults such as viral, allergen, and pollutant exposure and impaired repair responses leads to asthma persistence and provides the mediator and growth factor microenvironment for persistence of inflammation and airway wall remodeling. Increased deposition of matrix in the epithelial lamina reticularis provides evidence for ongoing epithelial barrier dysfunction, while physical distortion of the epithelium consequent upon repeated bronchoconstriction provides additional stimuli for remodeling. This latter response initially serves a protective function but, if exaggerated, may lead to fixed airflow obstruction associated with more severe and chronic disease. Dual pathways in the origins, persistence, and progression of asthma help explain why anti-inflammatory treatments fail to influence the natural history of asthma in childhood and only partially does so in chronic severe disease. Positioning the airway epithelium as fundamental to the origins and persistence of asthma provides a rationale for pursuit of therapeutics that increase the resistance of the airways to environmental insults rather than concentrating all effort on suppressing inflammation.. asthma| epithelium| inflammation| remodeling| environmental injury| origins| progression| phenotypes|epidermal-growth-factor| thymic stromal lymphopoietin| reticular basement-membrane| goblet cell hyperplasia| chemokine receptor 4| bronchial-asthma| dendritic cells| increased expression| childhood asthma| tight junctions.	JUL-2011	asthma| epithelium| inflammation| remodeling| environmental injury| origins| progression| phenotypes|epidermal-growth-factor| thymic stromal lymphopoietin| reticular basement-membrane| goblet cell hyperplasia| chemokine receptor 4| bronchial-asthma| dendritic cells| increased expression| childhood asthma| tight junctions	Holgate, ST	The sentinel role of the airway epithelium in asthma pathogenesis		IMMUNOLOGICAL REVIEWS	asthma; epithelium; inflammation; remodeling; environmental injury; origins; progression; phenotypes	EPIDERMAL-GROWTH-FACTOR; THYMIC STROMAL LYMPHOPOIETIN; RETICULAR BASEMENT-MEMBRANE; GOBLET CELL HYPERPLASIA; CHEMOKINE RECEPTOR 4; BRONCHIAL-ASTHMA; DENDRITIC CELLS; INCREASED EXPRESSION; CHILDHOOD ASTHMA; TIGHT JUNCTIONS	The adoption of the concept that asthma is primarily a disease most frequently associated with elaboration of T-helper 2 (Th2)-type inflammation has led to the widely held concept that its origins, exacerbation, and persistence are allergen driven. Taking aside the asthma that is expressed in non-allergic individuals leaves the great proportion of asthma that is associated with allergy (or atopy) and that often has its onset in early childhood. Evidence is presented that asthma is primarily an epithelial disorder and that its origin as well as its clinical manifestations have more to do with altered epithelial physical and functional barrier properties than being purely linked to allergic pathways. In genetically susceptible individuals, impaired epithelial barrier function renders the airways vulnerable to early life virus infection, and this in turn provides the stimulus to prime immature dendritic cells toward directing a Th2 response and local allergen sensitization. Continued epithelial susceptibility to environmental insults such as viral, allergen, and pollutant exposure and impaired repair responses leads to asthma persistence and provides the mediator and growth factor microenvironment for persistence of inflammation and airway wall remodeling. Increased deposition of matrix in the epithelial lamina reticularis provides evidence for ongoing epithelial barrier dysfunction, while physical distortion of the epithelium consequent upon repeated bronchoconstriction provides additional stimuli for remodeling. This latter response initially serves a protective function but, if exaggerated, may lead to fixed airflow obstruction associated with more severe and chronic disease. Dual pathways in the origins, persistence, and progression of asthma help explain why anti-inflammatory treatments fail to influence the natural history of asthma in childhood and only partially does so in chronic severe disease. Positioning the airway epithelium as fundamental to the origins and persistence of asthma provides a rationale for pursuit of therapeutics that increase the resistance of the airways to environmental insults rather than concentrating all effort on suppressing inflammation.	176	174	2011	15	10.1111/j.1600-065X.2011.01030.x	Immunology
Endotoxin exposure, CD14, and allergic disease - An interaction between genes and the environment. Rationale: High endotoxin exposure may reduce the risk of allergic sensitization. Objective: To determine the relationship between a promoter polymorphism in the CD14 gene (CD14/-159 C to T) and endotoxin exposure in relation to the development of allergic sensitization, eczema, and wheeze within the setting of a birth cohort. Methods: We genotyped 442 children (CD14/-159 C to T; rs2569190). We assessed children for allergic sensitization (IgE > 0.2 kU/L to at least one of seven allergens), eczema (physical examination), and parentally reported wheeze. Endotoxin was measured in house dust. Main Results: Genotype frequencies were consistent with other populations (TT, 25%; CT, 47%; CC, 28%). Sensitization (present in 33% of children) was not associated with genotype. For children with TT and CT genotypes, there was no association between endo toxin and sensitization (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.71-1.23; p = 0.7; and OR, 0.90; 95% CI, 0.77-1.04; p = 0.16, respectively) or endotoxin and eczema (OR, 0.99; 95% CI, 0.81-1.20; p = 0.89; and OR, 1.38; 95% CI, 0.83-2.30; p = 0.22, respectively). In children with the genotype CC, increasing endotoxin load was associated with a marked and significant reduction in the risk of sensitization (OR, 0.70; 95% CI, 0.55-0.89; p = 0.004) and eczema (OR, 0.73; 95% CI, 0.56-0.95; p = 0.02). However, we observed an increased risk of nonatopic wheeze with increasing endotoxin exposure in children with the CC genotype (OR, 1.42; 95% CI, 1.01-1.99; p = 0.04) but not other genotypes. No effect was seen for atopic wheeze. Conclusions: Increasing enclotoxin exposure is associated with reduced risk of allergic sensitization and eczema but with increased risk of nonatopic wheeze in children with the CC genotype at -159 of the CD14 gene. The impact of environmental enclotoxin may be enhanced in individuals with this genotype.. allergy| asthma| genetics|serum immunoglobulin-e| house-dust| promoter polymorphism| soluble cd14| manchester asthma| receptor cd14| ige levels| early-life| hay-fever| atopy.	AUG 15-2006	allergy| asthma| genetics|serum immunoglobulin-e| house-dust| promoter polymorphism| soluble cd14| manchester asthma| receptor cd14| ige levels| early-life| hay-fever| atopy	Simpson, A; John, SL; Jury, F; Niven, R; Woodcock, A; Ollier, WER; Custovic, A	Endotoxin exposure, CD14, and allergic disease - An interaction between genes and the environment		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	allergy; asthma; genetics	SERUM IMMUNOGLOBULIN-E; HOUSE-DUST; PROMOTER POLYMORPHISM; SOLUBLE CD14; MANCHESTER ASTHMA; RECEPTOR CD14; IGE LEVELS; EARLY-LIFE; HAY-FEVER; ATOPY	Rationale: High endotoxin exposure may reduce the risk of allergic sensitization. Objective: To determine the relationship between a promoter polymorphism in the CD14 gene (CD14/-159 C to T) and endotoxin exposure in relation to the development of allergic sensitization, eczema, and wheeze within the setting of a birth cohort. Methods: We genotyped 442 children (CD14/-159 C to T; rs2569190). We assessed children for allergic sensitization (IgE > 0.2 kU/L to at least one of seven allergens), eczema (physical examination), and parentally reported wheeze. Endotoxin was measured in house dust. Main Results: Genotype frequencies were consistent with other populations (TT, 25%; CT, 47%; CC, 28%). Sensitization (present in 33% of children) was not associated with genotype. For children with TT and CT genotypes, there was no association between endo toxin and sensitization (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.71-1.23; p = 0.7; and OR, 0.90; 95% CI, 0.77-1.04; p = 0.16, respectively) or endotoxin and eczema (OR, 0.99; 95% CI, 0.81-1.20; p = 0.89; and OR, 1.38; 95% CI, 0.83-2.30; p = 0.22, respectively). In children with the genotype CC, increasing endotoxin load was associated with a marked and significant reduction in the risk of sensitization (OR, 0.70; 95% CI, 0.55-0.89; p = 0.004) and eczema (OR, 0.73; 95% CI, 0.56-0.95; p = 0.02). However, we observed an increased risk of nonatopic wheeze with increasing endotoxin exposure in children with the CC genotype (OR, 1.42; 95% CI, 1.01-1.99; p = 0.04) but not other genotypes. No effect was seen for atopic wheeze. Conclusions: Increasing enclotoxin exposure is associated with reduced risk of allergic sensitization and eczema but with increased risk of nonatopic wheeze in children with the CC genotype at -159 of the CD14 gene. The impact of environmental enclotoxin may be enhanced in individuals with this genotype.	50	174	2006	7	10.1164/rccm.200509-1380OC	General & Internal Medicine; Respiratory System
Assessment of the safety of foods derived from genetically modified (GM) crops. This paper provides guidance on how to assess the safety of foods derived from genetically modified crops (GM crops); it summarises conclusions and recommendations of Working Group I of the ENTRANSFOOD project. The paper provides an approach for adapting the test strategy to the characteristics of the modified crop and the introduced trait, and assessing potential unintended effects from the genetic modification. The proposed approach to safety assessment starts with the comparison of the new GM crop with a traditional counterpart that is generally accepted as safe based on a history of human food use (the concept of substantial equivalence). This case-focused approach ensures that foods derived from GM crops that have passed this extensive test-regime are as safe and nutritious as currently consumed plant-derived foods. The approach is suitable for current and future GM crops with more complex modifications. First, the paper reviews test methods developed for the risk assessment of chemicals, including food additives and pesticides, discussing which of these methods are suitable for the assessment of recombinant proteins and whole foods. Second, the paper presents a systematic approach to combine test methods for the safety assessment of foods derived from a specific GM crop. Third, the paper provides an overview on developments in this area that may prove of use in the safety assess-merit of GM crops, and recommendations for research priorities. It is concluded that the combination of existing test methods provides a sound test-regime to assess the safety of GM crops. Advances in our understanding of molecular biology, biochemistry, and nutrition may in future allow further improvement of test methods that will over time render the safety assessment of foods even more effective and informative. (C) 2004 Elsevier Ltd. All rights reserved.. food| plant biotechnology| genetic modification| genetic engineering| genetic manipulation| transgenic crops| novel foods| recombinant proteins| plant metabolism| regulation| safety assessment| risk analysis| molecular characterisation| toxicology| allergy| substantial equivalence| unintended effects| bioinformatics| in vitro test methods| in vivo test methods| animal testing| post market monitoring| estimated consumption| exposure assessment| compositional analysis| advanced analytical methods| profiling|selectable marker genes| in-vitro toxicology| beta-lactoglobulin| rice genome| intrachromosomal recombination| potential allergenicity| conventional cottonseed| substantial equivalence| protein allergenicity| consumption surveys.	JUL-2004	food| plant biotechnology| genetic modification| genetic engineering| genetic manipulation| transgenic crops| novel foods| recombinant proteins| plant metabolism| regulation| safety assessment| risk analysis| molecular characterisation| toxicology| allergy| substantial equivalence| unintended effects| bioinformatics| in vitro test methods| in vivo test methods| animal testing| post market monitoring| estimated consumption| exposure assessment| compositional analysis| advanced analytical methods| profiling|selectable marker genes| in-vitro toxicology| beta-lactoglobulin| rice genome| intrachromosomal recombination| potential allergenicity| conventional cottonseed| substantial equivalence| protein allergenicity| consumption surveys	Konig, A; Cockburn, A; Crevel, RWR; Debruyne, E; Grafstroem, R; Hammerling, U; Kimber, I; Knudsen, I; Kuiper, HA; Peijnenburg, AACM; Penninks, AH; Poulsen, M; Schauzu, M; Wal, JM	Assessment of the safety of foods derived from genetically modified (GM) crops		FOOD AND CHEMICAL TOXICOLOGY	food; plant biotechnology; genetic modification; genetic engineering; genetic manipulation; transgenic crops; novel foods; recombinant proteins; plant metabolism; regulation; safety assessment; risk analysis; molecular characterisation; toxicology; allergy; substantial equivalence; unintended effects; bioinformatics; in vitro test methods; in vivo test methods; animal testing; post market monitoring; estimated consumption; exposure assessment; compositional analysis; advanced analytical methods; profiling	SELECTABLE MARKER GENES; IN-VITRO TOXICOLOGY; BETA-LACTOGLOBULIN; RICE GENOME; INTRACHROMOSOMAL RECOMBINATION; POTENTIAL ALLERGENICITY; CONVENTIONAL COTTONSEED; SUBSTANTIAL EQUIVALENCE; PROTEIN ALLERGENICITY; CONSUMPTION SURVEYS	This paper provides guidance on how to assess the safety of foods derived from genetically modified crops (GM crops); it summarises conclusions and recommendations of Working Group I of the ENTRANSFOOD project. The paper provides an approach for adapting the test strategy to the characteristics of the modified crop and the introduced trait, and assessing potential unintended effects from the genetic modification. The proposed approach to safety assessment starts with the comparison of the new GM crop with a traditional counterpart that is generally accepted as safe based on a history of human food use (the concept of substantial equivalence). This case-focused approach ensures that foods derived from GM crops that have passed this extensive test-regime are as safe and nutritious as currently consumed plant-derived foods. The approach is suitable for current and future GM crops with more complex modifications. First, the paper reviews test methods developed for the risk assessment of chemicals, including food additives and pesticides, discussing which of these methods are suitable for the assessment of recombinant proteins and whole foods. Second, the paper presents a systematic approach to combine test methods for the safety assessment of foods derived from a specific GM crop. Third, the paper provides an overview on developments in this area that may prove of use in the safety assess-merit of GM crops, and recommendations for research priorities. It is concluded that the combination of existing test methods provides a sound test-regime to assess the safety of GM crops. Advances in our understanding of molecular biology, biochemistry, and nutrition may in future allow further improvement of test methods that will over time render the safety assessment of foods even more effective and informative. (C) 2004 Elsevier Ltd. All rights reserved.	183	174	2004	42	10.1016/j.fct.2004.02.019	Food Science & Technology; Toxicology
Epidemiologic evidence for asthma and exposure to air toxics: Linkages between occupational, indoor, and community air pollution research. Outdoor ambient air pollutant exposures in communities are relevant to the acute exacerbation and possibly the onset of asthma. However, the complexity of pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to identify causal components in those mixtures. Occupational exposures associated with asthma may yield clues to causal components in ambient air pollution because such exposures are often identifiable as single-chemical agents (e.g., metal compounds). However, translating occupational to community exposure-response relationships is limited. Of the air toxics found to cause occupational asthma, only formaldehyde has been frequently investigated in epidemiologic studies of allergic respiratory responses to indoor air, where general consistency can be shown despite lower ambient exposures. The specific volatile organic compounds (VOCs) identified in association with occupational asthma are generally not the same as those in studies showing respiratory effects of VOC mixtures on nonoccupational adult and pediatric asthma. In addition, experimental evidence indicates that airborne polycyclic aromatic hydrocarbon (PAH) exposures linked to diesel exhaust particles (DEPs) have proinflammatory effects on airways, but there is insufficient supporting evidence from the occupational literature of effects of DEPs on asthma or lung function. In contrast, nonoccupational epidemiologic studies have frequently shown associations between allergic responses or asthma with exposures to ambient air pollutant mixtures with PAH components, including black smoke, high home or school traffic density (particularly truck traffic), and environmental tobacco smoke. Other particle-phase and gaseous co-pollutants are likely causal in these associations as well. Epidemiologic research on the relationship of both asthma onset and exacerbation to air pollution is needed to disentangle effects of air toxics; from monitored criteria air pollutants such as particle mass. Community studies should focus on air toxics expected to have adverse respiratory effects based on biological mechanisms, particularly irritant and immunological pathways to asthma onset and exacerbation.. asthma| diesel| epidemiology| toxic air pollutants| volatile organic compounds|diesel exhaust particles| environmental tobacco-smoke| volatile organic-compounds| chronic respiratory symptoms| lung-function growth| term ambient concentrations| nitrogen-dioxide exposure| bus garage workers| childhood asthma| automobile exhaust.	AUG-2002	asthma| diesel| epidemiology| toxic air pollutants| volatile organic compounds|diesel exhaust particles| environmental tobacco-smoke| volatile organic-compounds| chronic respiratory symptoms| lung-function growth| term ambient concentrations| nitrogen-dioxide exposure| bus garage workers| childhood asthma| automobile exhaust	Delfino, RJ	Epidemiologic evidence for asthma and exposure to air toxics: Linkages between occupational, indoor, and community air pollution research		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; diesel; epidemiology; toxic air pollutants; volatile organic compounds	DIESEL EXHAUST PARTICLES; ENVIRONMENTAL TOBACCO-SMOKE; VOLATILE ORGANIC-COMPOUNDS; CHRONIC RESPIRATORY SYMPTOMS; LUNG-FUNCTION GROWTH; TERM AMBIENT CONCENTRATIONS; NITROGEN-DIOXIDE EXPOSURE; BUS GARAGE WORKERS; CHILDHOOD ASTHMA; AUTOMOBILE EXHAUST	Outdoor ambient air pollutant exposures in communities are relevant to the acute exacerbation and possibly the onset of asthma. However, the complexity of pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to identify causal components in those mixtures. Occupational exposures associated with asthma may yield clues to causal components in ambient air pollution because such exposures are often identifiable as single-chemical agents (e.g., metal compounds). However, translating occupational to community exposure-response relationships is limited. Of the air toxics found to cause occupational asthma, only formaldehyde has been frequently investigated in epidemiologic studies of allergic respiratory responses to indoor air, where general consistency can be shown despite lower ambient exposures. The specific volatile organic compounds (VOCs) identified in association with occupational asthma are generally not the same as those in studies showing respiratory effects of VOC mixtures on nonoccupational adult and pediatric asthma. In addition, experimental evidence indicates that airborne polycyclic aromatic hydrocarbon (PAH) exposures linked to diesel exhaust particles (DEPs) have proinflammatory effects on airways, but there is insufficient supporting evidence from the occupational literature of effects of DEPs on asthma or lung function. In contrast, nonoccupational epidemiologic studies have frequently shown associations between allergic responses or asthma with exposures to ambient air pollutant mixtures with PAH components, including black smoke, high home or school traffic density (particularly truck traffic), and environmental tobacco smoke. Other particle-phase and gaseous co-pollutants are likely causal in these associations as well. Epidemiologic research on the relationship of both asthma onset and exacerbation to air pollution is needed to disentangle effects of air toxics; from monitored criteria air pollutants such as particle mass. Community studies should focus on air toxics expected to have adverse respiratory effects based on biological mechanisms, particularly irritant and immunological pathways to asthma onset and exacerbation.	156	174	2002	17		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Although eosinophils have been implicated in the pathogenesis of gastrointestinal disorders, their function has not been established. Using a murine model of oral antigen-induced eosinophil-associated gastrointestinal disease, we report the pathological consequences of eosinophilic inflammation and the involvement of eotaxin and eosinophils, Exposure of mice to enteric-coated antigen promotes an extensive T helper 2-associated eosinophilic inflammatory response involving the esophagus, stomach, small intestine and Peyer's patches as well as the development of gastric dysmotility, gastromegaly and cachexia. Electron microscopy shows eosinophils in proximity to damaged axons, which indicated that eosinophils were mediating a pathologic response. In addition, mice deficient in eotaxin have impaired eosinophil recruitment and are protected from gastromegaly and cachexia. These results establish a critical pathological function for eotaxin and eosinophils in gastrointestinal allergic hypersensitivity.. major basic-protein| in-vivo| mucosal eosinophils| tissue eosinophilia| chemokine eotaxin| interferon-gamma| food allergy| gastroenteritis| disease| interleukin-5.	APR-2001	major basic-protein| in-vivo| mucosal eosinophils| tissue eosinophilia| chemokine eotaxin| interferon-gamma| food allergy| gastroenteritis| disease| interleukin-5	Hogan, SP; Mishra, A; Brandt, EB; Royalty, MP; Pope, SM; Zimmermann, N; Foster, PS; Rothenberg, ME	A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation		NATURE IMMUNOLOGY		MAJOR BASIC-PROTEIN; IN-VIVO; MUCOSAL EOSINOPHILS; TISSUE EOSINOPHILIA; CHEMOKINE EOTAXIN; INTERFERON-GAMMA; FOOD ALLERGY; GASTROENTERITIS; DISEASE; INTERLEUKIN-5	Although eosinophils have been implicated in the pathogenesis of gastrointestinal disorders, their function has not been established. Using a murine model of oral antigen-induced eosinophil-associated gastrointestinal disease, we report the pathological consequences of eosinophilic inflammation and the involvement of eotaxin and eosinophils, Exposure of mice to enteric-coated antigen promotes an extensive T helper 2-associated eosinophilic inflammatory response involving the esophagus, stomach, small intestine and Peyer's patches as well as the development of gastric dysmotility, gastromegaly and cachexia. Electron microscopy shows eosinophils in proximity to damaged axons, which indicated that eosinophils were mediating a pathologic response. In addition, mice deficient in eotaxin have impaired eosinophil recruitment and are protected from gastromegaly and cachexia. These results establish a critical pathological function for eotaxin and eosinophils in gastrointestinal allergic hypersensitivity.	47	174	2001	8	10.1038/86365	Immunology
"The exposure-response curve for ozone and risk of mortality and the adequacy of current ozone regulations. Time-series analyses have shown that ozone is associated with increased risk of premature mortality, but little is known about how O-3 affects health at low concentrations. A critical scientific and policy question is whether a threshold level exists below which O-3 does not adversely affect mortality. We developed and applied several statistical models to data on air pollution, weather, and mortality for 98 U.S. urban communities for the period 1987-2000 to estimate the exposure-response curve for tropospheric O-3 and risk of mortality and to evaluate whether a ""safe"" threshold level exists. Methods included a linear approach and subset, threshold, and spline models. All results indicate that any threshold would exist at very low concentrations, far below current U.S. and international regulations and nearing background levels. For example, under a scenario in which the U.S. Environmental Protection Agency's 8-hr regulation is met every day in each community, there was still a 0.30% increase in mortality per 10-ppb increase in the average of the same and previous days' O-3 levels (95% posterior interval, 0.15-0.45%). Our findings indicate that even low levels of tropospheric O-3 are associated with increased risk of premature mortality. Interventions to further reduce O-3 pollution would benefit public health, even in regions that meet current regulatory standards and guidelines.. mortality| ozone| regulations| threshold|distributed lag models| largest us cities| air-pollution| particulate matter| ambient ozone| health| children| asthma."	APR-2006	mortality| ozone| regulations| threshold|distributed lag models| largest us cities| air-pollution| particulate matter| ambient ozone| health| children| asthma	Bell, ML; Peng, RD; Dominici, F	The exposure-response curve for ozone and risk of mortality and the adequacy of current ozone regulations		ENVIRONMENTAL HEALTH PERSPECTIVES	mortality; ozone; regulations; threshold	DISTRIBUTED LAG MODELS; LARGEST US CITIES; AIR-POLLUTION; PARTICULATE MATTER; AMBIENT OZONE; HEALTH; CHILDREN; ASTHMA	"Time-series analyses have shown that ozone is associated with increased risk of premature mortality, but little is known about how O-3 affects health at low concentrations. A critical scientific and policy question is whether a threshold level exists below which O-3 does not adversely affect mortality. We developed and applied several statistical models to data on air pollution, weather, and mortality for 98 U.S. urban communities for the period 1987-2000 to estimate the exposure-response curve for tropospheric O-3 and risk of mortality and to evaluate whether a ""safe"" threshold level exists. Methods included a linear approach and subset, threshold, and spline models. All results indicate that any threshold would exist at very low concentrations, far below current U.S. and international regulations and nearing background levels. For example, under a scenario in which the U.S. Environmental Protection Agency's 8-hr regulation is met every day in each community, there was still a 0.30% increase in mortality per 10-ppb increase in the average of the same and previous days' O-3 levels (95% posterior interval, 0.15-0.45%). Our findings indicate that even low levels of tropospheric O-3 are associated with increased risk of premature mortality. Interventions to further reduce O-3 pollution would benefit public health, even in regions that meet current regulatory standards and guidelines."	43	173	2006	5	10.1289/ehp.8816	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Effects of an Anti-TSLP Antibody on Allergen-Induced Asthmatic Responses. BACKGROUND Thymic stromal lymphopoietin (TSLP) is an epithelial-cell-derived cytokine that may be important in initiating allergic inflammation. AMG 157 is a human anti-TSLP monoclonal immunoglobulin G2 lambda that binds human TSLP and prevents receptor interaction. METHODS In this double-blind, placebo-controlled study, we randomly assigned 31 patients with mild allergic asthma to receive three monthly doses of AMG 157 (700 mg) or placebo intravenously. We conducted allergen challenges on days 42 and 84 to evaluate the effect of AMG 157 in reducing the maximum percentage decrease in the forced expiratory volume in 1 second (FEV1). We also measured the fraction of nitric oxide in exhaled air, blood and sputum eosinophils, and airway hyperresponsiveness. The primary end point was the late asthmatic response, as measured 3 to 7 hours after the allergen challenge. RESULTS AMG 157 attenuated most measures of allergen-induced early and late asthmatic responses. The maximum percentage decrease in the FEV1 during the late response was 34.0% smaller in the AMG-157 group than in the placebo group on day 42 (P=0.09) and 45.9% smaller on day 84 (P=0.02). In addition, patients receiving AMG 157 had significant decreases in levels of blood and sputum eosinophils before and after the allergen challenge and in the fraction of exhaled nitric oxide. There were 15 adverse events in the AMG-157 group, as compared with 12 in the placebo group; there were no serious adverse events. CONCLUSIONS Treatment with AMG 157 reduced allergen-induced bronchoconstriction and indexes of airway inflammation before and after allergen challenge. These findings are consistent with a key role for TSLP in allergen-induced airway responses and persistent airway inflammation in patients with allergic asthma. Whether anti-TSLP therapeutics will have clinical value cannot be determined from these data. (Funded by Amgen; ClinicalTrials.gov number, NCT01405963.). thymic stromal lymphopoietin| induced airway responses| human epithelial-cells| mast-cells| inflammation| sputum| reproducibility| responsiveness| mepolizumab| expression.	MAY 29-2014	thymic stromal lymphopoietin| induced airway responses| human epithelial-cells| mast-cells| inflammation| sputum| reproducibility| responsiveness| mepolizumab| expression	Gauvreau, GM; O'Byrne, PM; Boulet, LP; Wang, Y; Cockcroft, D; Bigler, J; FitzGerald, JM; Boedigheimer, M; Davis, BE; Dias, C; Gorski, KS; Smith, L; Bautista, E; Comeau, MR; Leigh, R; Parnes, JR	Effects of an Anti-TSLP Antibody on Allergen-Induced Asthmatic Responses		NEW ENGLAND JOURNAL OF MEDICINE		THYMIC STROMAL LYMPHOPOIETIN; INDUCED AIRWAY RESPONSES; HUMAN EPITHELIAL-CELLS; MAST-CELLS; INFLAMMATION; SPUTUM; REPRODUCIBILITY; RESPONSIVENESS; MEPOLIZUMAB; EXPRESSION	BACKGROUND Thymic stromal lymphopoietin (TSLP) is an epithelial-cell-derived cytokine that may be important in initiating allergic inflammation. AMG 157 is a human anti-TSLP monoclonal immunoglobulin G2 lambda that binds human TSLP and prevents receptor interaction. METHODS In this double-blind, placebo-controlled study, we randomly assigned 31 patients with mild allergic asthma to receive three monthly doses of AMG 157 (700 mg) or placebo intravenously. We conducted allergen challenges on days 42 and 84 to evaluate the effect of AMG 157 in reducing the maximum percentage decrease in the forced expiratory volume in 1 second (FEV1). We also measured the fraction of nitric oxide in exhaled air, blood and sputum eosinophils, and airway hyperresponsiveness. The primary end point was the late asthmatic response, as measured 3 to 7 hours after the allergen challenge. RESULTS AMG 157 attenuated most measures of allergen-induced early and late asthmatic responses. The maximum percentage decrease in the FEV1 during the late response was 34.0% smaller in the AMG-157 group than in the placebo group on day 42 (P=0.09) and 45.9% smaller on day 84 (P=0.02). In addition, patients receiving AMG 157 had significant decreases in levels of blood and sputum eosinophils before and after the allergen challenge and in the fraction of exhaled nitric oxide. There were 15 adverse events in the AMG-157 group, as compared with 12 in the placebo group; there were no serious adverse events. CONCLUSIONS Treatment with AMG 157 reduced allergen-induced bronchoconstriction and indexes of airway inflammation before and after allergen challenge. These findings are consistent with a key role for TSLP in allergen-induced airway responses and persistent airway inflammation in patients with allergic asthma. Whether anti-TSLP therapeutics will have clinical value cannot be determined from these data. (Funded by Amgen; ClinicalTrials.gov number, NCT01405963.)	42	172	2014	9	10.1056/NEJMoa1402895	General & Internal Medicine
Health and environmental consequences of the world trade center disaster. The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperractivity. Evaluation of 10,116 firefighters showed exposure-related. P increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on I I September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster.. air pollution| airway hyperresponsiveness| asbestos| occupational lung disease| pm2.5| pm10| small for gestational age (sga)|new-york-city| fine particulate matter| 11th terrorist attacks| center site| malignant mesothelioma| lower manhattan| air-pollution| fetal-growth| center cough| ground-zero.	MAY-2004	air pollution| airway hyperresponsiveness| asbestos| occupational lung disease| pm2.5| pm10| small for gestational age (sga)|new-york-city| fine particulate matter| 11th terrorist attacks| center site| malignant mesothelioma| lower manhattan| air-pollution| fetal-growth| center cough| ground-zero	Landrigan, PJ; Lioy, PJ; Thurston, G; Berkowitz, G; Chen, LC; Chillrud, SN; Gavett, SH; Georgopoulos, PG; Geyh, AS; Levin, S; Perera, F; Rappaport, SM; Small, C	Health and environmental consequences of the world trade center disaster		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; airway hyperresponsiveness; asbestos; occupational lung disease; PM2.5; PM10; small for gestational age (SGA)	NEW-YORK-CITY; FINE PARTICULATE MATTER; 11TH TERRORIST ATTACKS; CENTER SITE; MALIGNANT MESOTHELIOMA; LOWER MANHATTAN; AIR-POLLUTION; FETAL-GROWTH; CENTER COUGH; GROUND-ZERO	The attack on the World Trade Center (WTC) created an acute environmental disaster of enormous magnitude. This study characterizes the environmental exposures resulting from destruction of the WTC and assesses their effects on health. Methods include ambient air sampling; analyses of outdoor and indoor settled dust; high-altitude imaging and modeling of the atmospheric plume; inhalation studies of WTC dust in mice; and clinical examinations, community surveys, and prospective epidemiologic studies of exposed populations. WTC dust was found to consist predominantly (95%) of coarse particles and contained pulverized cement, glass fibers, asbestos, lead, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polychlorinated furans and dioxins. Airborne particulate levels were highest immediately after the attack and declined thereafter. Particulate levels decreased sharply with distance from the WTC. Dust pH was highly alkaline (pH 9.0-11.0). Mice exposed to WTC dust showed only moderate pulmonary inflammation but marked bronchial hyperractivity. Evaluation of 10,116 firefighters showed exposure-related. P increases in cough and bronchial hyperreactivity. Evaluation of 183 cleanup workers showed new-onset cough (33%), wheeze (18%), and phlegm production (24%). Increased frequency of new-onset cough, wheeze, and shortness of breath were also observed in community residents. Follow-up of 182 pregnant women who were either inside or near the WTC on I I September showed a 2-fold increase in small-for-gestational-age (SGA) infants. In summary, environmental exposures after the WTC disaster were associated with significant adverse effects on health. The high alkalinity of WTC dust produced bronchial hyperreactivity, persistent cough, and increased risk of asthma. Plausible causes of the observed increase in SGA infants include maternal exposures to PAH and particulates. Future risk of mesothelioma may be increased, particularly among workers and volunteers exposed occupationally to asbestos. Continuing follow-up of all exposed populations is required to document the long-term consequences of the disaster.	58	172	2004	9	10.1289/ehp.6702	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
COPD - Epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. COPD continues to cause a heavy health and economic burden both in the United states and around the world. Some of the risk factors for COPD are well-known and include smoking, occupational exposures, air pollution, airway hyperresponsiveness, asthma, and certain genetic variations, although many questions, such as why <20% of smokers develop significant airway obstruction, remain. Precise definitions of COPD vary and are frequently dependent on an accurate diagnosis of the problem by a physician. These differences in the definition of COPD can have large effects on the estimates of COPD in the population. Furthermore, evidence that COPD represents several different disease processes with potentially different interventions continues to emerge. In most 4 the world, COPD prevalence and mortality are still increasing and likely will continue to rise in response to increases in smoking, particularly by women and adolescents. Resources aimed at smoking cessation and prevention, COPD education and early detection, and better treatment will be of the most benefit in our continuing efforts against this important cause of morbidity and mortality.. copd| epidemiology| mortality| prevalence| risk factors|obstructive pulmonary-disease| air-flow obstruction| united-states| lung-disease| asthma| airways| health| burden| hyperresponsiveness| nutrition.	MAY-2002	copd| epidemiology| mortality| prevalence| risk factors|obstructive pulmonary-disease| air-flow obstruction| united-states| lung-disease| asthma| airways| health| burden| hyperresponsiveness| nutrition	Mannino, DM	COPD - Epidemiology, prevalence, morbidity and mortality, and disease heterogeneity		CHEST	COPD; epidemiology; mortality; prevalence; risk factors	OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; UNITED-STATES; LUNG-DISEASE; ASTHMA; AIRWAYS; HEALTH; BURDEN; HYPERRESPONSIVENESS; NUTRITION	COPD continues to cause a heavy health and economic burden both in the United states and around the world. Some of the risk factors for COPD are well-known and include smoking, occupational exposures, air pollution, airway hyperresponsiveness, asthma, and certain genetic variations, although many questions, such as why <20% of smokers develop significant airway obstruction, remain. Precise definitions of COPD vary and are frequently dependent on an accurate diagnosis of the problem by a physician. These differences in the definition of COPD can have large effects on the estimates of COPD in the population. Furthermore, evidence that COPD represents several different disease processes with potentially different interventions continues to emerge. In most 4 the world, COPD prevalence and mortality are still increasing and likely will continue to rise in response to increases in smoking, particularly by women and adolescents. Resources aimed at smoking cessation and prevention, COPD education and early detection, and better treatment will be of the most benefit in our continuing efforts against this important cause of morbidity and mortality.	41	172	2002	6	10.1378/chest.121.5_suppl.121S	General & Internal Medicine; Respiratory System
A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1(-/-) and ROR alpha-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.. immune defects| e-cadherin| human eosinophils| t-cells| inflammation| expression| disease| keratinocytes| filaggrin| insights.	DEC 16-2013	immune defects| e-cadherin| human eosinophils| t-cells| inflammation| expression| disease| keratinocytes| filaggrin| insights	Salimi, M; Barlow, JL; Saunders, SP; Xue, LZ; Gutowska-Owsiak, D; Wang, XW; Huang, LC; Johnson, D; Scanlon, ST; McKenzie, ANJ; Fallon, PG; Ogg, GS	A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis		JOURNAL OF EXPERIMENTAL MEDICINE		IMMUNE DEFECTS; E-CADHERIN; HUMAN EOSINOPHILS; T-CELLS; INFLAMMATION; EXPRESSION; DISEASE; KERATINOCYTES; FILAGGRIN; INSIGHTS	Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1(-/-) and ROR alpha-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.	44	171	2013	12	10.1084/jem.20130351	Immunology; Research & Experimental Medicine
IL-33-Responsive Lineage(-)CD25(+)CD44(hi) Lymphoid Cells Mediate Innate Type 2 Immunity and Allergic Inflammation in the Lungs. Innate immunity provides the first line of response to invading pathogens and a variety of environmental insults. Recent studies identified novel subsets of innate lymphoid cells that are capable of mediating immune responses in mucosal organs. In this paper, we describe a subset of lymphoid cells that is involved in innate type 2 immunity in the lungs. Airway exposure of naive BALB/c or C57BL/6J mice to IL-33 results in a rapid (<12 h) production of IL-5 and IL-13 and marked airway eosinophilia independently of adaptive immunity. In the lungs of nonsensitized naive mice, IL-33-responsive cells were identified that have a lymphoid morphology, lack lineage markers, highly express CD25, CD44, Thy1.2, ICOS, Sca-1, and IL-7R alpha (i.e., Lin(-)CD25(+)D44(hi) lymphoid cells), and require IL-7Ra for their development. Airway exposure of naive mice to a clinically relevant ubiquitous fungal allergen, Alternaria alternata, increases bronchoalveolar lavage levels of IL-33, followed by IL-5 and IL-13 production and airway eosinophilia without T or B cells. This innate type 2 response to the allergen is nearly abolished in mice deficient in IL-33R (i.e., ST2), and the Lin(-)CD25(+)CD44(hi) lymphoid cells in the lungs are required and sufficient to mediate the response. Thus, a subset of innate immune cells that responds to IL-33 and vigorously produces Th2-type cytokines is present in mouse lungs. These cells may provide a novel mechanism for type 2 immunity in the airways and induction of allergic airway diseases such as asthma. The Journal of Immunology, 2012, 188: 1503-1513.. airway inflammation| cytokine production| mast-cells| t-cells| asthma| il-33| responses| receptor| family| st2.	FEB 1-2012	airway inflammation| cytokine production| mast-cells| t-cells| asthma| il-33| responses| receptor| family| st2	Bartemes, KR; Iijima, K; Kobayashi, T; Kephart, GM; McKenzie, AN; Kita, H	IL-33-Responsive Lineage(-)CD25(+)CD44(hi) Lymphoid Cells Mediate Innate Type 2 Immunity and Allergic Inflammation in the Lungs		JOURNAL OF IMMUNOLOGY		AIRWAY INFLAMMATION; CYTOKINE PRODUCTION; MAST-CELLS; T-CELLS; ASTHMA; IL-33; RESPONSES; RECEPTOR; FAMILY; ST2	Innate immunity provides the first line of response to invading pathogens and a variety of environmental insults. Recent studies identified novel subsets of innate lymphoid cells that are capable of mediating immune responses in mucosal organs. In this paper, we describe a subset of lymphoid cells that is involved in innate type 2 immunity in the lungs. Airway exposure of naive BALB/c or C57BL/6J mice to IL-33 results in a rapid (<12 h) production of IL-5 and IL-13 and marked airway eosinophilia independently of adaptive immunity. In the lungs of nonsensitized naive mice, IL-33-responsive cells were identified that have a lymphoid morphology, lack lineage markers, highly express CD25, CD44, Thy1.2, ICOS, Sca-1, and IL-7R alpha (i.e., Lin(-)CD25(+)D44(hi) lymphoid cells), and require IL-7Ra for their development. Airway exposure of naive mice to a clinically relevant ubiquitous fungal allergen, Alternaria alternata, increases bronchoalveolar lavage levels of IL-33, followed by IL-5 and IL-13 production and airway eosinophilia without T or B cells. This innate type 2 response to the allergen is nearly abolished in mice deficient in IL-33R (i.e., ST2), and the Lin(-)CD25(+)CD44(hi) lymphoid cells in the lungs are required and sufficient to mediate the response. Thus, a subset of innate immune cells that responds to IL-33 and vigorously produces Th2-type cytokines is present in mouse lungs. These cells may provide a novel mechanism for type 2 immunity in the airways and induction of allergic airway diseases such as asthma. The Journal of Immunology, 2012, 188: 1503-1513.	50	171	2012	11	10.4049/jimmunol.1102832	Immunology
"A National Profile of the Health Care Experiences and Family Impact of Autism Spectrum Disorder Among Children in the United States, 2005-2006. OBJECTIVES. We sought to examine the health care experiences of children with autism spectrum disorder and the impact of autism spectrum disorder on the family and to assess whether having a medical home is associated with less family impact. METHODS. We used the 2005-2006 National Survey of Children With Special Health Care Needs to compare 2088 children with special health care needs, aged 3 to 17 years, reported by their parents to have autism spectrum disorder, with children with special health care needs with ""other emotional, developmental, or behavioral problems"" (excluding autism spectrum disorder; n = 9534) and 26 751 other children with special health care needs. We used weighted logistic regression to examine unmet needs for specific health care and support services, delayed care, no usual care source or personal physician, difficulty receiving referrals, and financial, employment, or time problems because of child's care. RESULTS. Nationally, an estimated 535 000 children have special health care needs and autism spectrum disorder, a prevalence of 86 per 10 000 children aged 3 to 17 years. Among children with special health care needs, 5.6% have autism spectrum disorder. Compared with other children with special health care needs without emotional, developmental, or behavioral problems, children with special health care needs with autism spectrum disorder were more likely to have unmet needs for specific health care services, family support services, delayed or foregone care, difficulty receiving referrals, and care that is not family centered. Children with special health care needs with autism spectrum disorder were more likely to live in families that report financial problems, need additional income for the child's medical care, reduce or stop work because of the child's condition, spend >= 10 hours per week providing or coordinating care, and paid more than $1000 in the previous year for the child's care. The financial impacts of autism spectrum disorder were significantly more burdensome when children with special health care needs did not have a medical home. CONCLUSIONS. Children with special health care needs with autism spectrum disorder are significantly more likely to have problems regarding access to care and unmet needs, and their families have greater financial, employment, and time burdens compared with other children with special health care needs. Receipt of primary care in a medical home may reduce these burdens. Pediatrics 2008; 122: e1149-e1158. autism spectrum disorder| children with special health care needs| disability| national estimates| access to health care|pervasive developmental disorders| parental report| medical home| needs| prevalence| expenditures| access| services| support| asthma."	DEC-2008	autism spectrum disorder| children with special health care needs| disability| national estimates| access to health care|pervasive developmental disorders| parental report| medical home| needs| prevalence| expenditures| access| services| support| asthma	Kogan, MD; Strickland, BB; Blumberg, SJ; Singh, GK; Perrin, JM; van Dyck, PC	A National Profile of the Health Care Experiences and Family Impact of Autism Spectrum Disorder Among Children in the United States, 2005-2006		PEDIATRICS	autism spectrum disorder; children with special health care needs; disability; national estimates; access to health care	PERVASIVE DEVELOPMENTAL DISORDERS; PARENTAL REPORT; MEDICAL HOME; NEEDS; PREVALENCE; EXPENDITURES; ACCESS; SERVICES; SUPPORT; ASTHMA	"OBJECTIVES. We sought to examine the health care experiences of children with autism spectrum disorder and the impact of autism spectrum disorder on the family and to assess whether having a medical home is associated with less family impact. METHODS. We used the 2005-2006 National Survey of Children With Special Health Care Needs to compare 2088 children with special health care needs, aged 3 to 17 years, reported by their parents to have autism spectrum disorder, with children with special health care needs with ""other emotional, developmental, or behavioral problems"" (excluding autism spectrum disorder; n = 9534) and 26 751 other children with special health care needs. We used weighted logistic regression to examine unmet needs for specific health care and support services, delayed care, no usual care source or personal physician, difficulty receiving referrals, and financial, employment, or time problems because of child's care. RESULTS. Nationally, an estimated 535 000 children have special health care needs and autism spectrum disorder, a prevalence of 86 per 10 000 children aged 3 to 17 years. Among children with special health care needs, 5.6% have autism spectrum disorder. Compared with other children with special health care needs without emotional, developmental, or behavioral problems, children with special health care needs with autism spectrum disorder were more likely to have unmet needs for specific health care services, family support services, delayed or foregone care, difficulty receiving referrals, and care that is not family centered. Children with special health care needs with autism spectrum disorder were more likely to live in families that report financial problems, need additional income for the child's medical care, reduce or stop work because of the child's condition, spend >= 10 hours per week providing or coordinating care, and paid more than $1000 in the previous year for the child's care. The financial impacts of autism spectrum disorder were significantly more burdensome when children with special health care needs did not have a medical home. CONCLUSIONS. Children with special health care needs with autism spectrum disorder are significantly more likely to have problems regarding access to care and unmet needs, and their families have greater financial, employment, and time burdens compared with other children with special health care needs. Receipt of primary care in a medical home may reduce these burdens. Pediatrics 2008; 122: e1149-e1158"	61	171	2008	10	10.1542/peds.2008-1057	Pediatrics
Respiratory symptoms, pulmonary function, and markers of inflammation among bar workers before and after a legislative ban on smoking in public places. Context Scotland prohibited smoking in confined public places on March 26, 2006. Objective To investigate the association of smoke-free legislation with symptoms, pulmonary function, and markers of inflammation of bar workers. Design, Setting, and Participants This prospective observational study was conducted in Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed the study per protocol. Main Outcome Measures Respiratory and sensory symptoms, spirometry measurements, serum cotinine levels, peripheral inflammatory cell count, asthma qualityof-life scores, and exhaled nitric oxide levels were evaluated before and after introduction of the smoking ban. Results For the per-protocol analysis, the percentage of bar workers with respiratory and sensory symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n = 41) (total change, -26%; 95% confidence interval [CI], -13.8% to -38.1%; P < .001) and 46.8% (n = 38) (-32.5%; 95% CI, -19.8% to -45.2%; P < .001) 1 and 2 months afterward. Forced expiratory volume in the first second increased from 96.6% predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P , .001) and then 101.7% (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels decreased from 5.15 ng/mL to 3.22 ng/mL (change, -1.93 ng/mL; 95% CI, -2.83 to -1.03 ng/mL; P < .001) and then 2.93 ng/mL (-2.22 ng/mL; 95% CI, -3.10 to -1.34 ng/ mL; P < .001). The total white blood cell and neutrophil count was reduced from 7610 to 6980 cells/mu L at 2 months (-630 cells/mu L; 95% CI, - 1010 to - 260 cells/mu L; P = .002) and from 4440 to 4030 cells/mu L (-410 cells/mu L; 95% CI, - 740 to - 90 cells/mu L; P = .03), respectively. Asthmatic bar workers also had less airway inflammation, with a reduction in exhaled nitric oxide from 34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change; 95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049). Conclusions Smoke-free legislation was associated with significant early improvements in symptoms, spirometry measurements, and systemic inflammation of bar workers. Asthmatic bar workers also had reduced airway inflammation and improved quality of life.. environmental tobacco-smoke| exhaled nitric-oxide| secondhand smoke| lung-function| passive smoking| bronchial responsiveness| airway inflammation| parental smoking| exposure| asthma.	OCT 11-2006	environmental tobacco-smoke| exhaled nitric-oxide| secondhand smoke| lung-function| passive smoking| bronchial responsiveness| airway inflammation| parental smoking| exposure| asthma	Menzies, D; Nair, A; Williamson, PA; Schembri, S; Al-Khairalla, MZH; Barnes, M; Fardon, TC; McFarlane, L; Magee, GJ; Lipworth, BJ	Respiratory symptoms, pulmonary function, and markers of inflammation among bar workers before and after a legislative ban on smoking in public places		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		ENVIRONMENTAL TOBACCO-SMOKE; EXHALED NITRIC-OXIDE; SECONDHAND SMOKE; LUNG-FUNCTION; PASSIVE SMOKING; BRONCHIAL RESPONSIVENESS; AIRWAY INFLAMMATION; PARENTAL SMOKING; EXPOSURE; ASTHMA	Context Scotland prohibited smoking in confined public places on March 26, 2006. Objective To investigate the association of smoke-free legislation with symptoms, pulmonary function, and markers of inflammation of bar workers. Design, Setting, and Participants This prospective observational study was conducted in Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed the study per protocol. Main Outcome Measures Respiratory and sensory symptoms, spirometry measurements, serum cotinine levels, peripheral inflammatory cell count, asthma qualityof-life scores, and exhaled nitric oxide levels were evaluated before and after introduction of the smoking ban. Results For the per-protocol analysis, the percentage of bar workers with respiratory and sensory symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n = 41) (total change, -26%; 95% confidence interval [CI], -13.8% to -38.1%; P < .001) and 46.8% (n = 38) (-32.5%; 95% CI, -19.8% to -45.2%; P < .001) 1 and 2 months afterward. Forced expiratory volume in the first second increased from 96.6% predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P , .001) and then 101.7% (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels decreased from 5.15 ng/mL to 3.22 ng/mL (change, -1.93 ng/mL; 95% CI, -2.83 to -1.03 ng/mL; P < .001) and then 2.93 ng/mL (-2.22 ng/mL; 95% CI, -3.10 to -1.34 ng/ mL; P < .001). The total white blood cell and neutrophil count was reduced from 7610 to 6980 cells/mu L at 2 months (-630 cells/mu L; 95% CI, - 1010 to - 260 cells/mu L; P = .002) and from 4440 to 4030 cells/mu L (-410 cells/mu L; 95% CI, - 740 to - 90 cells/mu L; P = .03), respectively. Asthmatic bar workers also had less airway inflammation, with a reduction in exhaled nitric oxide from 34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change; 95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049). Conclusions Smoke-free legislation was associated with significant early improvements in symptoms, spirometry measurements, and systemic inflammation of bar workers. Asthmatic bar workers also had reduced airway inflammation and improved quality of life.	36	171	2006	7	10.1001/jama.296.14.1742	General & Internal Medicine
NOD1 variation, immunoglobulin E and asthma. Asthma is a familial inflammatory disease of the airways of the lung. Microbial exposures in childhood protect against asthma through unknown mechanisms. The innate immune system is able to identify microbial components through a variety of pattern-recognition receptors (PRRs). NOD1 is an intracellular PRR that initiates inflammation in response to bacterial diaminopimelic acid (iE-DAP). The NOD1 gene is on chromosome 7p14, in a region that has been genetically linked to asthma. We carried out a systematic search for polymorphism in the gene. We found an insertion-deletion polymorphism (ND1+32656) near the beginning of intron IX that accounted for similar to 7% of the variation in IgE in two panels of families (P < 0.0005 in each). Allele*2 (the insertion) was associated with high IgE levels. The same allele was strongly associated with asthma in an independent study of 600 asthmatic children and 1194 super-normal controls [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.4-28.3, dominant model]. Differential binding of the two ND1+32656 alleles was observed to a protein from nuclei of the Calu 3 epithelial cell line. In an accompanying study, the deletion allele (ND1+32656*1) was found to be associated with inflammatory bowel disease. The results indicate that intracellular recognition of specific bacterial products affects the presence of childhood asthma.. quantitative traits| founder population| crohns-disease| association| gene| susceptibility| polymorphisms| locus| ige| responsiveness.	APR 1-2005	quantitative traits| founder population| crohns-disease| association| gene| susceptibility| polymorphisms| locus| ige| responsiveness	Hysi, P; Kabesch, M; Moffatt, MF; Schedel, M; Carr, D; Zhang, YM; Boardman, B; von Mutius, E; Weiland, SK; Leupold, W; Fritzsch, C; Klopp, N; Musk, AW; James, A; Nunez, G; Inohara, N; Cookson, WOC	NOD1 variation, immunoglobulin E and asthma		HUMAN MOLECULAR GENETICS		QUANTITATIVE TRAITS; FOUNDER POPULATION; CROHNS-DISEASE; ASSOCIATION; GENE; SUSCEPTIBILITY; POLYMORPHISMS; LOCUS; IGE; RESPONSIVENESS	Asthma is a familial inflammatory disease of the airways of the lung. Microbial exposures in childhood protect against asthma through unknown mechanisms. The innate immune system is able to identify microbial components through a variety of pattern-recognition receptors (PRRs). NOD1 is an intracellular PRR that initiates inflammation in response to bacterial diaminopimelic acid (iE-DAP). The NOD1 gene is on chromosome 7p14, in a region that has been genetically linked to asthma. We carried out a systematic search for polymorphism in the gene. We found an insertion-deletion polymorphism (ND1+32656) near the beginning of intron IX that accounted for similar to 7% of the variation in IgE in two panels of families (P < 0.0005 in each). Allele*2 (the insertion) was associated with high IgE levels. The same allele was strongly associated with asthma in an independent study of 600 asthmatic children and 1194 super-normal controls [odds ratio (OR) 6.3; 95% confidence interval (CI) 1.4-28.3, dominant model]. Differential binding of the two ND1+32656 alleles was observed to a protein from nuclei of the Calu 3 epithelial cell line. In an accompanying study, the deletion allele (ND1+32656*1) was found to be associated with inflammatory bowel disease. The results indicate that intracellular recognition of specific bacterial products affects the presence of childhood asthma.	34	171	2005	7	10.1093/hmg/ddi087	Biochemistry & Molecular Biology; Genetics & Heredity
Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator-activated receptors (PPARs), PPAK-alpha and PPAR-gamma, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced air-way hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-alpha and -gamma are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-alpha and -gamma (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response.. nuclear receptors| asthma| eosinophils| ige| adcc|stem-cell factor| fc-epsilon-ri| nf-kappa-b| ppar-gamma| gene-expression| airway hyperresponsiveness| endothelial-cells| t-lymphocytes| mast-cells| dendritic cells.	AUG 4-2003	nuclear receptors| asthma| eosinophils| ige| adcc|stem-cell factor| fc-epsilon-ri| nf-kappa-b| ppar-gamma| gene-expression| airway hyperresponsiveness| endothelial-cells| t-lymphocytes| mast-cells| dendritic cells	Woerly, G; Honda, K; Loyens, M; Papin, JP; Auwerx, J; Staels, B; Capron, M; Dombrowicz, D	Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation		JOURNAL OF EXPERIMENTAL MEDICINE	nuclear receptors; asthma; eosinophils; IgE; ADCC	STEM-CELL FACTOR; FC-EPSILON-RI; NF-KAPPA-B; PPAR-GAMMA; GENE-EXPRESSION; AIRWAY HYPERRESPONSIVENESS; ENDOTHELIAL-CELLS; T-LYMPHOCYTES; MAST-CELLS; DENDRITIC CELLS	Allergic asthma is characterized by airway hyperresponsiveness, eosinophilia, and mucus accumulation and is associated with increased IgE concentrations. We demonstrate here that peroxisome proliferator-activated receptors (PPARs), PPAK-alpha and PPAR-gamma, which have been shown recently to be involved in the regulation of various cell types within the immune system, decrease antigen-induced air-way hyperresponsiveness, lung inflammation, eosinophilia, cytokine production, and GATA-3 expression as well as serum levels of antigen-specific IgE in a murine model of human asthma. In addition, we demonstrate that PPAR-alpha and -gamma are expressed in eosinophils and their activation inhibits in vitro chemotaxis and antibody-dependent cellular cytotoxicity. Thus, PPAR-alpha and -gamma (co)agonists might be of therapeutic interest for the regulation of allergic or inflammatory reactions by targeting both regulatory and effector cells involved in the immune response.	68	171	2003	11	10.1084/jem.20021384	Immunology; Research & Experimental Medicine
Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. To evaluate whether acute effects of ozone, nitrogen dioxide, and particulates with mass median diameter less than 10 mum could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blinded design. Children with asthma (n = 158) who were residents of Mexico City were randomly given a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin Q or a placebo and were followed from October 1998 to April 2000. Pulmonary function tests were carried out twice a week in the morning. During the follow-up observation period, the mean 1-hour maximum ozone level was 102 ppb (SD = 47), and the mean 24-hour average PM10 level was 56.7 mug/m(3) (SD = 27.4). In children with moderate and severe asthma, ozone levels 1 day before spirometry were inversely associated significantly with forced expiratory flow (FEF25-75) (-13.32 ml/ second/10 ppb; p = 0.000), FEV1 (-4.59 ml/10 ppb; p = 0.036), and peak expiratory flow (PEF) (-15.01 ml/second/10 ppb; p = 0.04) in the placebo group after adjusting for potential confounding factors. No association between ozone and lung functions was observed in the supplement group. We observed significant differences in lung function decrements between groups for FEF25-75 and PEF. Our results suggest that supplementation with antioxidants might modulate the impact of ozone exposure on the small airways of children with moderate to severe asthma.. childhood asthma| antioxidants| air pollution| mexico|ozone exposure| vitamin-e| lipid-peroxidation| pulmonary-function| alpha-tocopherol| rhesus-monkeys| ascorbic-acid| mild asthma| mexico-city| glutathione.	SEP 1-2002	childhood asthma| antioxidants| air pollution| mexico|ozone exposure| vitamin-e| lipid-peroxidation| pulmonary-function| alpha-tocopherol| rhesus-monkeys| ascorbic-acid| mild asthma| mexico-city| glutathione	Romieu, I; Sienra-Monge, JJ; Ramirez-Aguilar, M; Tellez-Rojo, MM; Moreno-Macias, H; Reyes-Ruiz, NI; del Rio-Navarro, BE; Ruiz-Navarro, MX; Hatch, G; Slade, R; Hernandez-Avila, M	Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	childhood asthma; antioxidants; air pollution; Mexico	OZONE EXPOSURE; VITAMIN-E; LIPID-PEROXIDATION; PULMONARY-FUNCTION; ALPHA-TOCOPHEROL; RHESUS-MONKEYS; ASCORBIC-ACID; MILD ASTHMA; MEXICO-CITY; GLUTATHIONE	To evaluate whether acute effects of ozone, nitrogen dioxide, and particulates with mass median diameter less than 10 mum could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blinded design. Children with asthma (n = 158) who were residents of Mexico City were randomly given a daily supplement of vitamins (50 mg/day of vitamin E and 250 mg/day of vitamin Q or a placebo and were followed from October 1998 to April 2000. Pulmonary function tests were carried out twice a week in the morning. During the follow-up observation period, the mean 1-hour maximum ozone level was 102 ppb (SD = 47), and the mean 24-hour average PM10 level was 56.7 mug/m(3) (SD = 27.4). In children with moderate and severe asthma, ozone levels 1 day before spirometry were inversely associated significantly with forced expiratory flow (FEF25-75) (-13.32 ml/ second/10 ppb; p = 0.000), FEV1 (-4.59 ml/10 ppb; p = 0.036), and peak expiratory flow (PEF) (-15.01 ml/second/10 ppb; p = 0.04) in the placebo group after adjusting for potential confounding factors. No association between ozone and lung functions was observed in the supplement group. We observed significant differences in lung function decrements between groups for FEF25-75 and PEF. Our results suggest that supplementation with antioxidants might modulate the impact of ozone exposure on the small airways of children with moderate to severe asthma.	46	171	2002	7	10.1164/rccm.2112074	General & Internal Medicine; Respiratory System
Chronic cough 1 - Prevalence, pathogenesis, and causes of chronic cough. Cough is a reflex action of the respiratory tract that is used to clear the upper airways. Chronic cough lasting for more than 8 weeks is common in the community. The causes include cigarette smoking, exposure to cigarette smoke, and exposure to environmental pollution, especially particulates. Diseases causing chronic cough include asthma, eosinophilic bronchitis, gastro-oesophageal reflux disease, postnasal drip syndrome or rhinosinusitis, chronic obstructive pulmonary disease, pulmonary fibrosis, and bronchiectasis. Doctors should always work towards a clear diagnosis, considering common and rare illnesses. In some patients, no cause is identified, leading to the diagnosis of idiopathic cough. Chronic cough is often associated with an increased response to tussive agents such as capsaicin. Plastic changes in intrinsic and synaptic excitability in the brainstem, spine, or airway nerves can enhance the cough reflex, and can persist in the absence of the initiating cough event. Structural and inflammatory airway mucosal changes in non-asthmatic chronic cough could represent the cause or the traumatic response to repetitive coughing. Effective control of cough requires not only controlling the disease causing the cough but also desensitisation of cough pathways.. gastroesophageal-reflux disease| chronic nonproductive cough| chronic persistent cough| postnasal-drip-syndrome| cryptogenic fibrosing alveolitis| sole presenting manifestation| obstructive pulmonary-disease| bronchoalveolar lavage fluid| interstitial lung-disease| capsaicin-induced cough.	APR 19-2008	gastroesophageal-reflux disease| chronic nonproductive cough| chronic persistent cough| postnasal-drip-syndrome| cryptogenic fibrosing alveolitis| sole presenting manifestation| obstructive pulmonary-disease| bronchoalveolar lavage fluid| interstitial lung-disease| capsaicin-induced cough	Chung, KF; Pavord, ID	Chronic cough 1 - Prevalence, pathogenesis, and causes of chronic cough		LANCET		GASTROESOPHAGEAL-REFLUX DISEASE; CHRONIC NONPRODUCTIVE COUGH; CHRONIC PERSISTENT COUGH; POSTNASAL-DRIP-SYNDROME; CRYPTOGENIC FIBROSING ALVEOLITIS; SOLE PRESENTING MANIFESTATION; OBSTRUCTIVE PULMONARY-DISEASE; BRONCHOALVEOLAR LAVAGE FLUID; INTERSTITIAL LUNG-DISEASE; CAPSAICIN-INDUCED COUGH	Cough is a reflex action of the respiratory tract that is used to clear the upper airways. Chronic cough lasting for more than 8 weeks is common in the community. The causes include cigarette smoking, exposure to cigarette smoke, and exposure to environmental pollution, especially particulates. Diseases causing chronic cough include asthma, eosinophilic bronchitis, gastro-oesophageal reflux disease, postnasal drip syndrome or rhinosinusitis, chronic obstructive pulmonary disease, pulmonary fibrosis, and bronchiectasis. Doctors should always work towards a clear diagnosis, considering common and rare illnesses. In some patients, no cause is identified, leading to the diagnosis of idiopathic cough. Chronic cough is often associated with an increased response to tussive agents such as capsaicin. Plastic changes in intrinsic and synaptic excitability in the brainstem, spine, or airway nerves can enhance the cough reflex, and can persist in the absence of the initiating cough event. Structural and inflammatory airway mucosal changes in non-asthmatic chronic cough could represent the cause or the traumatic response to repetitive coughing. Effective control of cough requires not only controlling the disease causing the cough but also desensitisation of cough pathways.	151	170	2008	11	10.1016/S0140-6736(08)60595-4	General & Internal Medicine
Prevention of asthma during the first 5 years of life: A randomized controlled trial. Background: Early life exposures may be important in the development of asthma and allergic disease. Objective: To test house dust mite (HDM) avoidance and dietary fatty acid modification, implemented throughout the first 5 years of life, as interventions to prevent asthma and allergic disease. Methods: We recruited newborns with a family history of asthma antenatally and randomized them, separately, to HDM avoidance or control and to dietary modification or control. At age 5 years, they were assessed for asthma and eczema and had skin prick tests for atopy. Results: Of 616 children randomized, 516 (84%) were evaluated at age 5 years. The HDM avoidance intervention resulted in a 61% reduction in HDM allergen concentrations (mu g/g dust) in the child's bed but no difference in the prevalence of asthma, wheeze, or atopy (P > .1). The prevalence of eczema was higher in the active HDM avoidance group (26% vs 19%; P = .06). The ratio of omega-6 to omega-3 fatty acids in plasma was lower in the active diet group (5.8 vs 7.4; P < .0001). However, the prevalence of asthma, wheezing, eczema, or atopy did not differ between the diet groups (P > .1). Conclusion: Further research is required to establish whether other interventions can be recommended for the prevention of asthma and allergic disease. Clinical implications: House dust mite avoidance measures and dietary fatty acid modification, as implemented in this trial during infancy and early childhood, did not prevent the onset of asthma, eczema, or atopy in high-risk children.. allergen avoidance| omega-3 fatty acids| prevention| birth cohort| house dust mite|dust-mite allergen| fatty-acid modification| childhood asthma| atopic eczema| mattress encasings| prevalence| children| symptoms| risk| exposure.	JUL-2006	allergen avoidance| omega-3 fatty acids| prevention| birth cohort| house dust mite|dust-mite allergen| fatty-acid modification| childhood asthma| atopic eczema| mattress encasings| prevalence| children| symptoms| risk| exposure	Marks, GB; Mihrshahi, S; Kemp, AS; Tovey, ER; Webb, K; Almqvist, C; Ampon, RD; Crisafulli, D; Belousova, EG; Mellis, CM; Peat, JK; Leeder, SR	Prevention of asthma during the first 5 years of life: A randomized controlled trial		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen avoidance; omega-3 fatty acids; prevention; birth cohort; house dust mite	DUST-MITE ALLERGEN; FATTY-ACID MODIFICATION; CHILDHOOD ASTHMA; ATOPIC ECZEMA; MATTRESS ENCASINGS; PREVALENCE; CHILDREN; SYMPTOMS; RISK; EXPOSURE	Background: Early life exposures may be important in the development of asthma and allergic disease. Objective: To test house dust mite (HDM) avoidance and dietary fatty acid modification, implemented throughout the first 5 years of life, as interventions to prevent asthma and allergic disease. Methods: We recruited newborns with a family history of asthma antenatally and randomized them, separately, to HDM avoidance or control and to dietary modification or control. At age 5 years, they were assessed for asthma and eczema and had skin prick tests for atopy. Results: Of 616 children randomized, 516 (84%) were evaluated at age 5 years. The HDM avoidance intervention resulted in a 61% reduction in HDM allergen concentrations (mu g/g dust) in the child's bed but no difference in the prevalence of asthma, wheeze, or atopy (P > .1). The prevalence of eczema was higher in the active HDM avoidance group (26% vs 19%; P = .06). The ratio of omega-6 to omega-3 fatty acids in plasma was lower in the active diet group (5.8 vs 7.4; P < .0001). However, the prevalence of asthma, wheezing, eczema, or atopy did not differ between the diet groups (P > .1). Conclusion: Further research is required to establish whether other interventions can be recommended for the prevention of asthma and allergic disease. Clinical implications: House dust mite avoidance measures and dietary fatty acid modification, as implemented in this trial during infancy and early childhood, did not prevent the onset of asthma, eczema, or atopy in high-risk children.	35	170	2006	9	10.1016/j.jaci.2006.04.004	Allergy; Immunology
Traffic-related air pollution and respiratory health during the first 2 yrs of life. As part of an international collaborative study on the impact of Traffic-Related Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5 mum (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) were analysed. The German part of the TRAPCA study used data from subpopulations of two ongoing birth cohort studies (German Infant Nutrition Intervention Programme (GIN I) and Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA)) based in the city of Munich. Geographic information systems (GIS)-based exposure modelling was used to estimate traffic-related air pollutants at the birth addresses of 1,756 infants. Logistic regression was used to analyse possible health effects and potential confounding factors were adjusted for. The ranges in estimated exposures to PM2.5, PM2.5 absorbance, and NO2 were 11.9-21.9 mug.m(-3), 1.38-4.39x10(-5) m(-1), and 19.5-66.9 mug.m(3), respectively. Significant associations between these pollutants and cough without infection (odds ratio (OR) (95% confidence interval (CI): 1.34 (1.11-1.61), 1.32 (1.10-1.59), and 1.40 (1.12-1.75), respectively) and dry cough at night (OR (95% Cl): 1.31 (1.07-1.60), 1.27 (1.04-1.55), and 1.36 (1.07-1.74), respectively) in the first year of life were found. In the second year of life, these effects were attenuated. There was some indication of an association between traffic-related air pollution and symptoms of cough. Due to the very young age of the infants, it was too early to draw definitive conclusions from this for the development of asthma.. air pollution| geographic information systems| infants| respiratory symptoms| traffic|nitrogen-dioxide| east-germany| children| symptoms| asthma| exposure| pollutants| prevalence| particles| density.	APR-2002	air pollution| geographic information systems| infants| respiratory symptoms| traffic|nitrogen-dioxide| east-germany| children| symptoms| asthma| exposure| pollutants| prevalence| particles| density	Gehring, U; Cyrys, J; Sedlmeir, G; Brunekreef, B; Bellander, T; Fischer, P; Bauer, CP; Reinhardt, D; Wichmann, HE; Heinrich, J	Traffic-related air pollution and respiratory health during the first 2 yrs of life		EUROPEAN RESPIRATORY JOURNAL	air pollution; geographic information systems; infants; respiratory symptoms; traffic	NITROGEN-DIOXIDE; EAST-GERMANY; CHILDREN; SYMPTOMS; ASTHMA; EXPOSURE; POLLUTANTS; PREVALENCE; PARTICLES; DENSITY	As part of an international collaborative study on the impact of Traffic-Related Air Pollution on Childhood Asthma (TRAPCA), the health effects associated with long-term exposure to particles with a 50% cut-off aerodynamic diameter of 2.5 mum (PM2.5), PM2.5 absorbance, and nitrogen dioxide (NO2) were analysed. The German part of the TRAPCA study used data from subpopulations of two ongoing birth cohort studies (German Infant Nutrition Intervention Programme (GIN I) and Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA)) based in the city of Munich. Geographic information systems (GIS)-based exposure modelling was used to estimate traffic-related air pollutants at the birth addresses of 1,756 infants. Logistic regression was used to analyse possible health effects and potential confounding factors were adjusted for. The ranges in estimated exposures to PM2.5, PM2.5 absorbance, and NO2 were 11.9-21.9 mug.m(-3), 1.38-4.39x10(-5) m(-1), and 19.5-66.9 mug.m(3), respectively. Significant associations between these pollutants and cough without infection (odds ratio (OR) (95% confidence interval (CI): 1.34 (1.11-1.61), 1.32 (1.10-1.59), and 1.40 (1.12-1.75), respectively) and dry cough at night (OR (95% Cl): 1.31 (1.07-1.60), 1.27 (1.04-1.55), and 1.36 (1.07-1.74), respectively) in the first year of life were found. In the second year of life, these effects were attenuated. There was some indication of an association between traffic-related air pollution and symptoms of cough. Due to the very young age of the infants, it was too early to draw definitive conclusions from this for the development of asthma.	36	170	2002	9	10.1183/09031936.02.01182001	Respiratory System
A double-blinded, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 months' treatment and 18 months' posttreatment follow-up. Background: Because asthma is not a curable condition, the development of strategies for prevention of the disease has a high priority. Atopic dermatitis is a common precursor to the development of asthma, and 2 studies have suggested that the use of an H-1 receptor antagonist might reduce the development of asthma while the treatment is being administered, at least in subgroups with evidence of high IgE levels. However, no trial to date has conducted follow-up after the initial treatment has been stopped to establish whether the intervention has merely suppressed symptoms or truly prevented disease. Objective: We sought to establish whether the use of cetirizine compared with placebo for 18 months in infants with atopic dermatitis suppressed or truly delayed the onset of asthma, even after cessation of therapy. Methods: The Early Treatment of the Atopic Child study was a double-blinded, parallel-group, randomized trial of 0.25 mg/kg body weight cetirizine administered twice daily compared with placebo given to infants between I and 2 years of age with atopic dermatitis. After 18 months of treatment, follow-up continued for a further 18 months. This article reports the outcome over the full 3 years of follow-up and relates the outcomes to the allergic status on the basis of IgE antibody measurements at recruitment. Results: Although there was no difference in cumulative prevalence of asthma between active and placebo treatment in the intention-to-treat population (P = .7), those infants with evidence of sensitivity to house dust mite, grass pollen, or both who were treated with cetirizine were significantly less likely to have asthma compared with those treated with placebo over the 18 months of treatment (P = .005 and .002, respectively), and this effect was sustained for the grass pollen-sensitized infants over the full 36 months (P = .008). In the house dust mite-sensitized group there was a gradual narrowing of the difference between active and placebo treatment in terms of cumulative prevalence of asthma at the end of 36 months but no evidence of a rebound immediately after the treatment stopped (P = .04). In the placebo population there was a significantly higher risk of development of asthma in those sensitized at baseline to egg (relative risk, 1.4 [95% CI, 1.1-1.7]), house dust mite (relative risk, 1.6 [95% CI, 1.3-1.9%]), grass pollen (relative risk, 1.7 [95% CI, 1.4-2.1]), or cat (relative risk, 1.5 [95% CI, 1.2-1.9]). Early and persistent sensitization conferred a higher risk than transient or later sensitization. Conclusions: Cetirizine compared with placebo truly delays or, in some cases, prevents the development of asthma in a subgroup of infants with atopic dermatitis sensitized to grass pollen and, to a lesser extent, house dust mite. Further studies are required focusing specifically on sensitized groups to substantiate this finding. The study also highlights risk factors for asthma in infants with atopic dermatitis and indicates that early and persistent aeroallergen sensitization confers a higher risk than later development of sensitivity.. atopic dermatitis| asthma| prevention| house dust mite| grass pollen| cetirizine| antihistamine| children|allergic airway disease| young-children| cat allergen| risk| recruitment| challenge| childhood.	DEC-2001	atopic dermatitis| asthma| prevention| house dust mite| grass pollen| cetirizine| antihistamine| children|allergic airway disease| young-children| cat allergen| risk| recruitment| challenge| childhood	Warner, JO	A double-blinded, randomized, placebo-controlled trial of cetirizine in preventing the onset of asthma in children with atopic dermatitis: 18 months' treatment and 18 months' posttreatment follow-up		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopic dermatitis; asthma; prevention; house dust mite; grass pollen; cetirizine; antihistamine; children	ALLERGIC AIRWAY DISEASE; YOUNG-CHILDREN; CAT ALLERGEN; RISK; RECRUITMENT; CHALLENGE; CHILDHOOD	Background: Because asthma is not a curable condition, the development of strategies for prevention of the disease has a high priority. Atopic dermatitis is a common precursor to the development of asthma, and 2 studies have suggested that the use of an H-1 receptor antagonist might reduce the development of asthma while the treatment is being administered, at least in subgroups with evidence of high IgE levels. However, no trial to date has conducted follow-up after the initial treatment has been stopped to establish whether the intervention has merely suppressed symptoms or truly prevented disease. Objective: We sought to establish whether the use of cetirizine compared with placebo for 18 months in infants with atopic dermatitis suppressed or truly delayed the onset of asthma, even after cessation of therapy. Methods: The Early Treatment of the Atopic Child study was a double-blinded, parallel-group, randomized trial of 0.25 mg/kg body weight cetirizine administered twice daily compared with placebo given to infants between I and 2 years of age with atopic dermatitis. After 18 months of treatment, follow-up continued for a further 18 months. This article reports the outcome over the full 3 years of follow-up and relates the outcomes to the allergic status on the basis of IgE antibody measurements at recruitment. Results: Although there was no difference in cumulative prevalence of asthma between active and placebo treatment in the intention-to-treat population (P = .7), those infants with evidence of sensitivity to house dust mite, grass pollen, or both who were treated with cetirizine were significantly less likely to have asthma compared with those treated with placebo over the 18 months of treatment (P = .005 and .002, respectively), and this effect was sustained for the grass pollen-sensitized infants over the full 36 months (P = .008). In the house dust mite-sensitized group there was a gradual narrowing of the difference between active and placebo treatment in terms of cumulative prevalence of asthma at the end of 36 months but no evidence of a rebound immediately after the treatment stopped (P = .04). In the placebo population there was a significantly higher risk of development of asthma in those sensitized at baseline to egg (relative risk, 1.4 [95% CI, 1.1-1.7]), house dust mite (relative risk, 1.6 [95% CI, 1.3-1.9%]), grass pollen (relative risk, 1.7 [95% CI, 1.4-2.1]), or cat (relative risk, 1.5 [95% CI, 1.2-1.9]). Early and persistent sensitization conferred a higher risk than transient or later sensitization. Conclusions: Cetirizine compared with placebo truly delays or, in some cases, prevents the development of asthma in a subgroup of infants with atopic dermatitis sensitized to grass pollen and, to a lesser extent, house dust mite. Further studies are required focusing specifically on sensitized groups to substantiate this finding. The study also highlights risk factors for asthma in infants with atopic dermatitis and indicates that early and persistent aeroallergen sensitization confers a higher risk than later development of sensitivity.	20	170	2001	9	10.1067/mai.2001.120015	Allergy; Immunology
Gender bias in the diagnosis of COPD. Background: COPD is thought to be more prevalent among men than women, a finding usually attributed to higher smoking rates and more frequent occupational exposures of significance for men. However, smoking prevalence has increased among women and there is evidence that women may be more susceptible to the adverse pulmonary function effects of smoking than men. There may also be underdiagnosis and misdiagnosis of COPD in both sexes because objective measures of lung function are underused, Objectives: We undertook the present study to determine if there is gender bias in the diagnosis of COPD, such that women are less likely than men to receive a diagnosis of COPD, We also attempted to determine if underuse of I;ng function measurements was a factor in any bias detected. Methods: We surveyed a random sample of 192 primary-care physicians (96 American and 96 Canadian; 154 men and 38 women) using a hypothetical case presentation and a structured interview. The case of cough and dyspnea in a smoker was presented in six versions differing only in the age and sex of the patient. After presentation of the history and physical findings, physicians were asked to state the most probable diagnosis and to choose the diagnostic studies needed, Physicians were then presented with spirometric findings of moderate or severe obstruction without significant bronchodilator response, and the questions repeated. Finally, the negative outcome of an oral steroid trial was described. Results: Initially, COPD was given as the most probable diagnosis significantly more often for men than women (58% vs 42%; p < 0,05), The likelihood of a COPD diagnosis increased significantly and initial differences between sexes decreased as objective information was provided. After spirometry, COPD diagnosis rates for men and women were 74% vs 66% (p = not significant); after the steroid trial 85% vs 79% (p = not significant). Only 22% of physicians would have requested spirometry after the initial presentation, Conclusions: In North America, primary-care physicians underdiagnose COPD, particularly in women. Spirometry reduces the risk of underdiagnosis and gender bias but is underused.. asthma| misdiagnosis| physician decision making| spirometry| underdiagnosis|obstructive pulmonary-disease| inhaled corticosteroid use| asthma| difference| density| care| risk.	JUN-2001	asthma| misdiagnosis| physician decision making| spirometry| underdiagnosis|obstructive pulmonary-disease| inhaled corticosteroid use| asthma| difference| density| care| risk	Chapman, KR; Tashkin, DP; Pye, DJ	Gender bias in the diagnosis of COPD		CHEST	asthma; misdiagnosis; physician decision making; spirometry; underdiagnosis	OBSTRUCTIVE PULMONARY-DISEASE; INHALED CORTICOSTEROID USE; ASTHMA; DIFFERENCE; DENSITY; CARE; RISK	Background: COPD is thought to be more prevalent among men than women, a finding usually attributed to higher smoking rates and more frequent occupational exposures of significance for men. However, smoking prevalence has increased among women and there is evidence that women may be more susceptible to the adverse pulmonary function effects of smoking than men. There may also be underdiagnosis and misdiagnosis of COPD in both sexes because objective measures of lung function are underused, Objectives: We undertook the present study to determine if there is gender bias in the diagnosis of COPD, such that women are less likely than men to receive a diagnosis of COPD, We also attempted to determine if underuse of I;ng function measurements was a factor in any bias detected. Methods: We surveyed a random sample of 192 primary-care physicians (96 American and 96 Canadian; 154 men and 38 women) using a hypothetical case presentation and a structured interview. The case of cough and dyspnea in a smoker was presented in six versions differing only in the age and sex of the patient. After presentation of the history and physical findings, physicians were asked to state the most probable diagnosis and to choose the diagnostic studies needed, Physicians were then presented with spirometric findings of moderate or severe obstruction without significant bronchodilator response, and the questions repeated. Finally, the negative outcome of an oral steroid trial was described. Results: Initially, COPD was given as the most probable diagnosis significantly more often for men than women (58% vs 42%; p < 0,05), The likelihood of a COPD diagnosis increased significantly and initial differences between sexes decreased as objective information was provided. After spirometry, COPD diagnosis rates for men and women were 74% vs 66% (p = not significant); after the steroid trial 85% vs 79% (p = not significant). Only 22% of physicians would have requested spirometry after the initial presentation, Conclusions: In North America, primary-care physicians underdiagnose COPD, particularly in women. Spirometry reduces the risk of underdiagnosis and gender bias but is underused.	15	170	2001	5	10.1378/chest.119.6.1691	General & Internal Medicine; Respiratory System
Proteases Induce Production of Thymic Stromal Lymphopoietin by Airway Epithelial Cells through Protease-Activated Receptor-2. Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and triggers dendritic cell-mediated Th2-type inflammation. Although TSLP is up-regulated in epithelium of patients with asthma, the factors that control TSLP production have not been studied extensively. Because mouse models suggest roles for protease(s) in Th2-type immune responses, we hypothesized that proteases from airborne allergens may induce TSLP production in a human airway epithelial cell line, BEAS-2B. TSLP mRNA and protein were induced when BEAS-2B cells were exposed to prototypic proteases, namely, trypsin and papain. TSLP induction by trypsin required intact protease activity and also a protease-sensing G protein-coupled receptor, protease-activated receptor (PAR)-2; TSLP induction by papain was partially dependent on PAR-2. In humans, exposure to ubiquitous airborne fungi, such as Alternaria, is implicated in the development and exacerbation of asthma. When BEAS-2B cells or normal human bronchial epithelial cells were exposed to Alternaria extract, TSLP was potently induced. The TSLP-inducing activity of Alternaria was partially blocked by treating the extract with a cysteine protease inhibitor, E-64, or by infecting BEAS-2B cells with small interfering RNA for PAR-2. Protease-induced TSLP production by BEAS-2B cells was enhanced synergistically by IL-4 and abolished by IFN-gamma. These findings demonstrate that TSLP expression is induced in airway epithelial cells by exposure to allergen-derived proteases and that PAR-2 is involved in the process. By promoting TSLP production in the airways, proteases associated with airborne allergens may facilitate the development and/or exacerbation of Th2-type airway inflammation, particularly in allergic individuals. The Journal of Immunology, 2009, 183: 1427-1434.. nf-kappa-b| dust mite allergen| dendritic cells| cytokine production| adaptive immunity| human eosinophils| type-2 responses| inhaled antigen| ifn-gamma| asthma.	JUL 15-2009	nf-kappa-b| dust mite allergen| dendritic cells| cytokine production| adaptive immunity| human eosinophils| type-2 responses| inhaled antigen| ifn-gamma| asthma	Kouzaki, H; O'Grady, SM; Lawrence, CB; Kita, H	Proteases Induce Production of Thymic Stromal Lymphopoietin by Airway Epithelial Cells through Protease-Activated Receptor-2		JOURNAL OF IMMUNOLOGY		NF-KAPPA-B; DUST MITE ALLERGEN; DENDRITIC CELLS; CYTOKINE PRODUCTION; ADAPTIVE IMMUNITY; HUMAN EOSINOPHILS; TYPE-2 RESPONSES; INHALED ANTIGEN; IFN-GAMMA; ASTHMA	Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and triggers dendritic cell-mediated Th2-type inflammation. Although TSLP is up-regulated in epithelium of patients with asthma, the factors that control TSLP production have not been studied extensively. Because mouse models suggest roles for protease(s) in Th2-type immune responses, we hypothesized that proteases from airborne allergens may induce TSLP production in a human airway epithelial cell line, BEAS-2B. TSLP mRNA and protein were induced when BEAS-2B cells were exposed to prototypic proteases, namely, trypsin and papain. TSLP induction by trypsin required intact protease activity and also a protease-sensing G protein-coupled receptor, protease-activated receptor (PAR)-2; TSLP induction by papain was partially dependent on PAR-2. In humans, exposure to ubiquitous airborne fungi, such as Alternaria, is implicated in the development and exacerbation of asthma. When BEAS-2B cells or normal human bronchial epithelial cells were exposed to Alternaria extract, TSLP was potently induced. The TSLP-inducing activity of Alternaria was partially blocked by treating the extract with a cysteine protease inhibitor, E-64, or by infecting BEAS-2B cells with small interfering RNA for PAR-2. Protease-induced TSLP production by BEAS-2B cells was enhanced synergistically by IL-4 and abolished by IFN-gamma. These findings demonstrate that TSLP expression is induced in airway epithelial cells by exposure to allergen-derived proteases and that PAR-2 is involved in the process. By promoting TSLP production in the airways, proteases associated with airborne allergens may facilitate the development and/or exacerbation of Th2-type airway inflammation, particularly in allergic individuals. The Journal of Immunology, 2009, 183: 1427-1434.	57	169	2009	8	10.4049/jimmunol.0900904	Immunology
Allergic rhinitis and its impact on asthma update: Allergen immunotherapy. The Allergic Rhinitis and its Impact on Asthma document was first published in 2001. Since then, new data on specific immunotherapy have appeared. This review is intended as an update to the original document. MedLine (2001 to June 2006) was searched with appropriate key words, and panelists were asked to identify further relevant articles. Randomized controlled trials were considered for the evaluation of efficacy. For the evaluation of safety, and additional effects, studies with lower grades of evidence were included. The clinical efficacy of injection immunotherapy in rhinitis and asthma was confirmed, as well as the safety, provided that recommendations are followed. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the onset of new sensitizations. One randomized open trial demonstrated that in children with allergic rhinitis, injection immunotherapy may reduce the risk of developing asthma. There is strong evidence that sublingual immunotherapy is effective in allergic rhinitis in adults. Recent meta-analyses demonstrated its efficacy in allergic rhinitis in children and in asthma, although more definitive trials are required. Current data indicate that sublingual immunotherapy is safe and the rate of adverse reactions is not greater below 5 years of age. One randomized open trial showed that in children with allergic rhinitis, sublingual immunotherapy reduced the onset of asthma. Further studies are needed to identify the optimal maintenance dose and to elucidate the mechanism of action. Novel approaches for immunotherapy are currently under evaluation, including the use of adjuvants, peptides. and DNA-conjugated and recombinant allergens.. injection immunotherapy| sublingual immunotherapy| efficacy| safety| mechanisms|grass-pollen immunotherapy| house-dust-mite| sublingual-swallow immunotherapy| randomized controlled-trial| monophosphoryl-lipid-a| preseasonal-specific immunotherapy| systemic immunological changes| messenger-rna expression| placebo-controlled trial| double-blind.	APR-2007	injection immunotherapy| sublingual immunotherapy| efficacy| safety| mechanisms|grass-pollen immunotherapy| house-dust-mite| sublingual-swallow immunotherapy| randomized controlled-trial| monophosphoryl-lipid-a| preseasonal-specific immunotherapy| systemic immunological changes| messenger-rna expression| placebo-controlled trial| double-blind	Passalacqua, G; Durham, SR	Allergic rhinitis and its impact on asthma update: Allergen immunotherapy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	injection immunotherapy; sublingual immunotherapy; efficacy; safety; mechanisms	GRASS-POLLEN IMMUNOTHERAPY; HOUSE-DUST-MITE; SUBLINGUAL-SWALLOW IMMUNOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; MONOPHOSPHORYL-LIPID-A; PRESEASONAL-SPECIFIC IMMUNOTHERAPY; SYSTEMIC IMMUNOLOGICAL CHANGES; MESSENGER-RNA EXPRESSION; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND	The Allergic Rhinitis and its Impact on Asthma document was first published in 2001. Since then, new data on specific immunotherapy have appeared. This review is intended as an update to the original document. MedLine (2001 to June 2006) was searched with appropriate key words, and panelists were asked to identify further relevant articles. Randomized controlled trials were considered for the evaluation of efficacy. For the evaluation of safety, and additional effects, studies with lower grades of evidence were included. The clinical efficacy of injection immunotherapy in rhinitis and asthma was confirmed, as well as the safety, provided that recommendations are followed. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the onset of new sensitizations. One randomized open trial demonstrated that in children with allergic rhinitis, injection immunotherapy may reduce the risk of developing asthma. There is strong evidence that sublingual immunotherapy is effective in allergic rhinitis in adults. Recent meta-analyses demonstrated its efficacy in allergic rhinitis in children and in asthma, although more definitive trials are required. Current data indicate that sublingual immunotherapy is safe and the rate of adverse reactions is not greater below 5 years of age. One randomized open trial showed that in children with allergic rhinitis, sublingual immunotherapy reduced the onset of asthma. Further studies are needed to identify the optimal maintenance dose and to elucidate the mechanism of action. Novel approaches for immunotherapy are currently under evaluation, including the use of adjuvants, peptides. and DNA-conjugated and recombinant allergens.	144	169	2007	11	10.1016/j.jaci.2007.01.045	Allergy; Immunology
The September epidemic of asthma exacerbations in children: A search for etiology. Background: Predictable peaks of asthma exacerbation requiring hospital treatment, of greatest magnitude in children and of uncertain etiology, occur globally after school returns. Objective: We wished to determine whether asthmatic children requiring emergency department treatment for exacerbations after school return in September were more likely to have respiratory viruses present and less likely to have prescriptions for control medications than children with equally severe asthma not requiring emergent treatment. Methods: Rates of viral detection and characteristics of asthma management in 57 (of 60) children age 5 to 15 years presenting to emergency departments with asthma in 2 communities in Canada between September 10 and 30, 2001, (cases) were compared with those in 157 age-matched volunteer children with asthma of comparable severity studied simultaneously (controls). Results: Human picornaviruses were detected in 52% of cases and 29% of controls (P=.002) and viruses of any type in 62% of cases and 41% of controls (P =.011). Cases were less likely to have been prescribed controller medication (inhaled corticosteroid, 49% vs 85%; P <.0001; leukotriene receptor antagonist, 9% vs 21%; P =.04). Conclusion: Respiratory viruses were detected in the majority of children presenting to emergency departments with asthma during the September epidemic of the disease and in a significant minority of children with asthma in the community. The latter were more likely to have anti-inflammatory medication prescriptions than children requiring emergent treatment. Such medication may reduce the risk of emergency department treatment for asthma during the September epidemic.. asthma| children| viral infections| rhinovirus| school return| inhaled corticosteroid| leukotriene receptor antagonist|respiratory-infections| rhinovirus infections| hospital admission| childhood asthma| air-pollution| allergens| frequency| exposure| viruses| school.	JAN-2005	asthma| children| viral infections| rhinovirus| school return| inhaled corticosteroid| leukotriene receptor antagonist|respiratory-infections| rhinovirus infections| hospital admission| childhood asthma| air-pollution| allergens| frequency| exposure| viruses| school	Johnston, NW; Johnston, SL; Duncan, JM; Greene, JM; Kebadze, T; Keith, PK; Roy, M; Waserman, S; Sears, MR	The September epidemic of asthma exacerbations in children: A search for etiology		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; children; viral infections; rhinovirus; school return; inhaled corticosteroid; leukotriene receptor antagonist	RESPIRATORY-INFECTIONS; RHINOVIRUS INFECTIONS; HOSPITAL ADMISSION; CHILDHOOD ASTHMA; AIR-POLLUTION; ALLERGENS; FREQUENCY; EXPOSURE; VIRUSES; SCHOOL	Background: Predictable peaks of asthma exacerbation requiring hospital treatment, of greatest magnitude in children and of uncertain etiology, occur globally after school returns. Objective: We wished to determine whether asthmatic children requiring emergency department treatment for exacerbations after school return in September were more likely to have respiratory viruses present and less likely to have prescriptions for control medications than children with equally severe asthma not requiring emergent treatment. Methods: Rates of viral detection and characteristics of asthma management in 57 (of 60) children age 5 to 15 years presenting to emergency departments with asthma in 2 communities in Canada between September 10 and 30, 2001, (cases) were compared with those in 157 age-matched volunteer children with asthma of comparable severity studied simultaneously (controls). Results: Human picornaviruses were detected in 52% of cases and 29% of controls (P=.002) and viruses of any type in 62% of cases and 41% of controls (P =.011). Cases were less likely to have been prescribed controller medication (inhaled corticosteroid, 49% vs 85%; P <.0001; leukotriene receptor antagonist, 9% vs 21%; P =.04). Conclusion: Respiratory viruses were detected in the majority of children presenting to emergency departments with asthma during the September epidemic of the disease and in a significant minority of children with asthma in the community. The latter were more likely to have anti-inflammatory medication prescriptions than children requiring emergent treatment. Such medication may reduce the risk of emergency department treatment for asthma during the September epidemic.	36	169	2005	7	10.1016/j.jaci.2004.09.025	Allergy; Immunology
Dampness in buildings as a risk factor for health effects, EUROEXPO: a multidisciplinary review of the literature (1998-2000) on dampness and mite exposure in buildings and health effects. The scientific literature on health effects from dampness in buildings, including mite exposure over the period 1998-2000 has been reviewed by a European group (EUROEXPO) of eight scientists in experience from medicine, epidemiology, toxicology and engineering. Forty studies deemed relevant have been the foundation for the conclusions. Dampness in buildings is a risk factor for health effects among atopics and non-atopics both in domestic and in public environments. However, the literature is not conclusive in respect of causative agents, e.g. mites, microbiological agents and organic chemicals from degraded building materials. There is a strong need for more multidisciplinary studies including expertise from all relevant areas. A general conclusion from the work was that there is a strong need for multidisciplinary reviews in scientific journals of articles dealing with associations between indoor environmental factors and health effects.. indoor environment| damp buildings| mite exposure| health effects| review|house-dust-mite| indoor allergen levels| respiratory symptoms| atopic-dermatitis| school-children| childhood asthma| air-pollution| nasal lavage| bronchial hyperresponsiveness| systemic symptoms.	AUG-2004	indoor environment| damp buildings| mite exposure| health effects| review|house-dust-mite| indoor allergen levels| respiratory symptoms| atopic-dermatitis| school-children| childhood asthma| air-pollution| nasal lavage| bronchial hyperresponsiveness| systemic symptoms	Bornehag, CG; Sundell, J; Bonini, S; Custovic, A; Malmberg, P; Skerfving, S; Sigsgaard, T; Verhoeff, A	Dampness in buildings as a risk factor for health effects, EUROEXPO: a multidisciplinary review of the literature (1998-2000) on dampness and mite exposure in buildings and health effects		INDOOR AIR	indoor environment; damp buildings; mite exposure; health effects; review	HOUSE-DUST-MITE; INDOOR ALLERGEN LEVELS; RESPIRATORY SYMPTOMS; ATOPIC-DERMATITIS; SCHOOL-CHILDREN; CHILDHOOD ASTHMA; AIR-POLLUTION; NASAL LAVAGE; BRONCHIAL HYPERRESPONSIVENESS; SYSTEMIC SYMPTOMS	The scientific literature on health effects from dampness in buildings, including mite exposure over the period 1998-2000 has been reviewed by a European group (EUROEXPO) of eight scientists in experience from medicine, epidemiology, toxicology and engineering. Forty studies deemed relevant have been the foundation for the conclusions. Dampness in buildings is a risk factor for health effects among atopics and non-atopics both in domestic and in public environments. However, the literature is not conclusive in respect of causative agents, e.g. mites, microbiological agents and organic chemicals from degraded building materials. There is a strong need for more multidisciplinary studies including expertise from all relevant areas. A general conclusion from the work was that there is a strong need for multidisciplinary reviews in scientific journals of articles dealing with associations between indoor environmental factors and health effects.	107	169	2004	15	10.1111/j.1600-0668.2004.00240.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Background: Previous studies have suggested that sensitivity to Alternaria and Cladosporium may be risk factors for life-threatening asthma. We have investigated this by studying the relationship between skin tests for fungal spores and admission to atl intensive care unit (ICU) for asthma. Methods: Skin prick tests for fungal spores (Alternaria tenuis, Cladosporium cladosporoides, Helminthosporium maydis, and Epicoccum nigrum), cat dander, house-dust mite (Dermatophagoides pteronyssinus), and a seven-grass mix were performed in three groups of patients: patients admitted to an ICU with an attack of asthma; those who had received emergency treatment for asthma but had not been admitted to an ICU, and those who had never required emergency treatment for their asthma. Results: Twenty of 37 patients (54%) admitted to the ICU had a positive skin test for one or more fungal allergens compared with 15/50 patients (30%) in each of the other groups (P=0.005). The ICU patients were no more likely to have positive skin tests for the grass mix, cat dander, or house-dust mite than the other patients. Conclusions: a positive skin test for fungal allergens is a risk factor for admission to an ICU with an acute attack of asthma.. asthma| fungal allergens|fatal asthma.	MAY-2000	asthma| fungal allergens|fatal asthma	Black, PN; Udy, AA; Brodie, SM	Sensitivity to fungal allergens is a risk factor for life-threatening asthma		ALLERGY	asthma; fungal allergens	FATAL ASTHMA	Background: Previous studies have suggested that sensitivity to Alternaria and Cladosporium may be risk factors for life-threatening asthma. We have investigated this by studying the relationship between skin tests for fungal spores and admission to atl intensive care unit (ICU) for asthma. Methods: Skin prick tests for fungal spores (Alternaria tenuis, Cladosporium cladosporoides, Helminthosporium maydis, and Epicoccum nigrum), cat dander, house-dust mite (Dermatophagoides pteronyssinus), and a seven-grass mix were performed in three groups of patients: patients admitted to an ICU with an attack of asthma; those who had received emergency treatment for asthma but had not been admitted to an ICU, and those who had never required emergency treatment for their asthma. Results: Twenty of 37 patients (54%) admitted to the ICU had a positive skin test for one or more fungal allergens compared with 15/50 patients (30%) in each of the other groups (P=0.005). The ICU patients were no more likely to have positive skin tests for the grass mix, cat dander, or house-dust mite than the other patients. Conclusions: a positive skin test for fungal allergens is a risk factor for admission to an ICU with an acute attack of asthma.	16	169	2000	4	10.1034/j.1398-9995.2000.00293.x	Allergy; Immunology
Defective epithelial barrier function in asthma. Background: Asthma is a complex disease involving gene and environment interactions. Although atopy is a strong predisposing risk factor for asthma, local tissue susceptibilities are required for disease expression. The bronchial epithelium forms the interface with the external environment and is pivotally involved in controlling tissue homeostasis through provision of a physical barrier controlled by tight junction (TJ) complexes. Objectives: To explain the link between environment exposures and airway vulnerability, we hypothesized that epithelial TJs are abnormal in asthma, leading to increased susceptibility to environmental agents. Methods: Localization of TJs in bronchial biopsies and differentiated epithelial cultures was assessed by electron microscopy or immunostaining. Baseline permeability and the effect of cigarette smoke and growth factor were assessed by measurement of transepithelial electrical resistance and passage of fluorescently labeled dextrans. Results: By using immunostaining, we found that bronchial biopsies from asthmatic subjects displayed patchy disruption of TJs. In differentiated bronchial epithelial cultures, TJ formation and transepithelial electrical resistance were significantly lower (P < .05) in cultures from asthmatic donors (n = 43) than from normal controls (n = 40) and inversely correlated with macromolecular permeability. Cultures from asthmatic donors were also more sensitive to disruption by cigarette smoke extract. Epidermal growth factor enhanced basal TJ formation in cultures from asthmatic subjects (P < .01) and protected against cigarette smoke-induced barrier disruption (P < .01). Conclusions: Our results show that the bronchial epithelial barrier in asthma is compromised. This defect may facilitate the passage of allergens and other agents into the airway tissue, leading to immune activation and may thus contribute to the end organ expression of asthma. (J Allergy Clin Immunol 2011;128:549-56.). tight junction| epidermal growth factor| cigarette smoke| asthma| epithelial barrier|epidermal-growth-factor| tight junctions| bronchial epithelium| ulcerative-colitis| factor receptor| erbb receptors| hegf levels| disease| cells| expression.	SEP-2011	tight junction| epidermal growth factor| cigarette smoke| asthma| epithelial barrier|epidermal-growth-factor| tight junctions| bronchial epithelium| ulcerative-colitis| factor receptor| erbb receptors| hegf levels| disease| cells| expression	Xiao, C; Puddicombe, SM; Field, S; Haywood, J; Broughton-Head, V; Puxeddu, I; Haitchi, HM; Vernon-Wilson, E; Sammut, D; Bedke, N; Cremin, C; Sones, J; Djukanovic, R; Howarth, PH; Collins, JE; Holgate, ST; Monk, P; Davies, DE	Defective epithelial barrier function in asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Tight junction; epidermal growth factor; cigarette smoke; asthma; epithelial barrier	EPIDERMAL-GROWTH-FACTOR; TIGHT JUNCTIONS; BRONCHIAL EPITHELIUM; ULCERATIVE-COLITIS; FACTOR RECEPTOR; ERBB RECEPTORS; HEGF LEVELS; DISEASE; CELLS; EXPRESSION	Background: Asthma is a complex disease involving gene and environment interactions. Although atopy is a strong predisposing risk factor for asthma, local tissue susceptibilities are required for disease expression. The bronchial epithelium forms the interface with the external environment and is pivotally involved in controlling tissue homeostasis through provision of a physical barrier controlled by tight junction (TJ) complexes. Objectives: To explain the link between environment exposures and airway vulnerability, we hypothesized that epithelial TJs are abnormal in asthma, leading to increased susceptibility to environmental agents. Methods: Localization of TJs in bronchial biopsies and differentiated epithelial cultures was assessed by electron microscopy or immunostaining. Baseline permeability and the effect of cigarette smoke and growth factor were assessed by measurement of transepithelial electrical resistance and passage of fluorescently labeled dextrans. Results: By using immunostaining, we found that bronchial biopsies from asthmatic subjects displayed patchy disruption of TJs. In differentiated bronchial epithelial cultures, TJ formation and transepithelial electrical resistance were significantly lower (P < .05) in cultures from asthmatic donors (n = 43) than from normal controls (n = 40) and inversely correlated with macromolecular permeability. Cultures from asthmatic donors were also more sensitive to disruption by cigarette smoke extract. Epidermal growth factor enhanced basal TJ formation in cultures from asthmatic subjects (P < .01) and protected against cigarette smoke-induced barrier disruption (P < .01). Conclusions: Our results show that the bronchial epithelial barrier in asthma is compromised. This defect may facilitate the passage of allergens and other agents into the airway tissue, leading to immune activation and may thus contribute to the end organ expression of asthma. (J Allergy Clin Immunol 2011;128:549-56.)	43	168	2011	20	10.1016/j.jaci.2011.05.038	Allergy; Immunology
Clinical course and prognosis of cow's milk allergy are dependent on milk-specific IgE status. Background: Large, prospective population-based studies on clinical course, development of tolerance, and risk for other atopy in children with cow's milk allergy (CMA) are lacking. Objective: We investigated the development of tolerance and the risk for asthma, rhinoconjunctivitis, atopic dermatitis, and sensitization in children with CMA followed to school age. Methods: We followed 118 children with CMA until recovery and repeatedly measured their sensitization to cow's milk (CM). At age 8.6 years, 94 allergic subjects and 80 control subjects from the same cohort were studied for atopic diseases and sensitization. In addition, the parents of 12 allergic subjects and 26 control children returned a questionnaire on atopy, respectively. Results: IgE-mediated CMA was detected in 86 (73%) children; at age 8.6 years, 13 (15%) had persistent CMA. All children with IgE-negative CMA were tolerant by age 5.0 years (P < .0001). Risk factors for persistent CMA at age 2.0 years were sensitization to CM at age 1.6 years (odds ratio, 6.3; 95% CI, 2.6-15.2), urticaria at diagnostic challenge (odds ratio, 3.3; 95% CI, 1.4-7.8), CM exposure at the maternity hospital (odds ratio, 3.2; 95% CI, 1.4-7.8), and early sensitization to egg (odds ratio, 2.8; 95% CI, 1.2-6.6). By age 8.6 years, children with IgE-positive CMA more frequently had asthma (31% vs 13%, P <= .01), rhinoconjunctivitis (66% vs 21%, P <= .001), atopic eczema (81% vs 26%, P <= .001), and sensitization to any allergen (88% vs 39%, P <= .001) than control subjects. CMA and family history of atopy were independent risk factors for atopic diseases, and CMA was also a risk factor for sensitization to inhalant allergens. Conclusion: IgE-mediated CMA often persists to school age and is a risk factor for other atopy; non-IgE-mediated CMA, by contrast, is a benign infantile condition.. cow's milk allergy| ige| sensitization| skin test| tolerance| atopy|follow-up| atopic-dermatitis| egg allergy| 4 regions| children| age| infants| sensitization| tolerance| food.	OCT-2005	cow's milk allergy| ige| sensitization| skin test| tolerance| atopy|follow-up| atopic-dermatitis| egg allergy| 4 regions| children| age| infants| sensitization| tolerance| food	Saarinen, KM; Pelkonen, AS; Makela, M; Savilahti, E	Clinical course and prognosis of cow's milk allergy are dependent on milk-specific IgE status		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	cow's milk allergy; IgE; sensitization; skin test; tolerance; atopy	FOLLOW-UP; ATOPIC-DERMATITIS; EGG ALLERGY; 4 REGIONS; CHILDREN; AGE; INFANTS; SENSITIZATION; TOLERANCE; FOOD	Background: Large, prospective population-based studies on clinical course, development of tolerance, and risk for other atopy in children with cow's milk allergy (CMA) are lacking. Objective: We investigated the development of tolerance and the risk for asthma, rhinoconjunctivitis, atopic dermatitis, and sensitization in children with CMA followed to school age. Methods: We followed 118 children with CMA until recovery and repeatedly measured their sensitization to cow's milk (CM). At age 8.6 years, 94 allergic subjects and 80 control subjects from the same cohort were studied for atopic diseases and sensitization. In addition, the parents of 12 allergic subjects and 26 control children returned a questionnaire on atopy, respectively. Results: IgE-mediated CMA was detected in 86 (73%) children; at age 8.6 years, 13 (15%) had persistent CMA. All children with IgE-negative CMA were tolerant by age 5.0 years (P < .0001). Risk factors for persistent CMA at age 2.0 years were sensitization to CM at age 1.6 years (odds ratio, 6.3; 95% CI, 2.6-15.2), urticaria at diagnostic challenge (odds ratio, 3.3; 95% CI, 1.4-7.8), CM exposure at the maternity hospital (odds ratio, 3.2; 95% CI, 1.4-7.8), and early sensitization to egg (odds ratio, 2.8; 95% CI, 1.2-6.6). By age 8.6 years, children with IgE-positive CMA more frequently had asthma (31% vs 13%, P <= .01), rhinoconjunctivitis (66% vs 21%, P <= .001), atopic eczema (81% vs 26%, P <= .001), and sensitization to any allergen (88% vs 39%, P <= .001) than control subjects. CMA and family history of atopy were independent risk factors for atopic diseases, and CMA was also a risk factor for sensitization to inhalant allergens. Conclusion: IgE-mediated CMA often persists to school age and is a risk factor for other atopy; non-IgE-mediated CMA, by contrast, is a benign infantile condition.	28	168	2005	7	10.1016/j.jaci.2005.06.018	Allergy; Immunology
Occupational asthma. Substantial epidemiologic and clinical evidence indicates that agents inhaled at work can induce asthma. In industrialized countries, occupational factors have been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma includes (1) immunologic occupational asthma (OA), characterized by a latency period before the onset of symptoms; (2) nonimmunologic OA, which occurs after single or multiple exposures to high concentrations of irritant materials; (3) work-aggravated asthma, which is preexisting or concurrent asthma exacerbated by workplace exposures; and (4) variant syndromes. Assessment of the work environment has improved, making it possible to measure concentrations of several high- and low-molecular-weight agents in the workplace. The identification of host factors, polymorphisms, and candidate genes associated with OA is in progress and may improve our understanding of mechanisms involved in OA. A reliable diagnosis of OA should be confirmed by objective testing early after its onset. Removal of the worker from exposure to the causal agent and treatment with inhaled glucocorticoids lead to a better outcome. Finally, strategies for preventing OA should be implemented and their cost-effectiveness examined.. asthma| management| risk| susceptibility| workplace|natural-rubber latex| exhaled nitric-oxide| work-related asthma| airways dysfunction syndrome| diisocyanate-induced asthma| health-care workers| western red cedar| exposure-response relationships| laboratory-animal workers| isocyanate-induced asthma.	AUG 1-2005	asthma| management| risk| susceptibility| workplace|natural-rubber latex| exhaled nitric-oxide| work-related asthma| airways dysfunction syndrome| diisocyanate-induced asthma| health-care workers| western red cedar| exposure-response relationships| laboratory-animal workers| isocyanate-induced asthma	Mapp, CE; Boschetto, P; Maestrelli, P; Fabbri, LM	Occupational asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; management; risk; susceptibility; workplace	NATURAL-RUBBER LATEX; EXHALED NITRIC-OXIDE; WORK-RELATED ASTHMA; AIRWAYS DYSFUNCTION SYNDROME; DIISOCYANATE-INDUCED ASTHMA; HEALTH-CARE WORKERS; WESTERN RED CEDAR; EXPOSURE-RESPONSE RELATIONSHIPS; LABORATORY-ANIMAL WORKERS; ISOCYANATE-INDUCED ASTHMA	Substantial epidemiologic and clinical evidence indicates that agents inhaled at work can induce asthma. In industrialized countries, occupational factors have been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma includes (1) immunologic occupational asthma (OA), characterized by a latency period before the onset of symptoms; (2) nonimmunologic OA, which occurs after single or multiple exposures to high concentrations of irritant materials; (3) work-aggravated asthma, which is preexisting or concurrent asthma exacerbated by workplace exposures; and (4) variant syndromes. Assessment of the work environment has improved, making it possible to measure concentrations of several high- and low-molecular-weight agents in the workplace. The identification of host factors, polymorphisms, and candidate genes associated with OA is in progress and may improve our understanding of mechanisms involved in OA. A reliable diagnosis of OA should be confirmed by objective testing early after its onset. Removal of the worker from exposure to the causal agent and treatment with inhaled glucocorticoids lead to a better outcome. Finally, strategies for preventing OA should be implemented and their cost-effectiveness examined.	435	168	2005	26	10.1164/rccm.200311-1575SO	General & Internal Medicine; Respiratory System
Cities as harbingers of climate change: Common ragweed, urbanization, and public health. Background: Although controlled laboratory experiments have been conducted to demonstrate the sensitivity of allergenic pollen production to future climatic change tie, increased CO2 and temperature), no in situ data are available. Objective: The purpose of this investigation was to assess, under realistic conditions, the impact of climatic change on pollen production of common ragweed, a ubiquitous weed occurring in disturbed sites and the principal source of pollen associated with seasonal allergenic rhinitis. Methods: We used an existing temperature/CO2 gradient between urban and rural areas to examine the quantitative and qualitative aspects of ragweed growth and pollen production. Results: For 2000 and 200 1, average daily (24-hour) values of CO2 concentration and air temperature within an urban environment were 30% to 31% and 1.8degrees to 2.0degreesC (3.4degrees to 3.6degreesF) higher than those at a rural site. This result is consistent with most global change scenarios. Ragweed grew faster, flowered earlier, and produced significantly greater above-ground biomass and ragweed pollen at urban locations than at rural locations. Conclusions: Here we show that 2 aspects of future global environmental change, air temperature and atmospheric CO2, are already significantly higher in urban relative to rural areas. In general, we show that regional urbanization-induced temperature/CO2 increases similar to those associated with projected global climatic change might already have public health consequences; we suggest that urbanization, per se, might provide a low-cost alternative to current experimental methods evaluating plant responses to climate change. (J Allergy Clin Immunol 2003;111:290-5.).. global change| seasonal allergenic rhinitis| amb a 1| common ragweed|co2 concentration| united-states| protein| allergy| aeroallergens| quantitation| nutrition| program| assay| usa.	FEB-2003	global change| seasonal allergenic rhinitis| amb a 1| common ragweed|co2 concentration| united-states| protein| allergy| aeroallergens| quantitation| nutrition| program| assay| usa	Ziska, LH; Gebhard, DE; Frenz, DA; Faulkner, S; Singer, BD; Straka, JG	Cities as harbingers of climate change: Common ragweed, urbanization, and public health		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	global change; seasonal allergenic rhinitis; Amb a 1; common ragweed	CO2 CONCENTRATION; UNITED-STATES; PROTEIN; ALLERGY; AEROALLERGENS; QUANTITATION; NUTRITION; PROGRAM; ASSAY; USA	Background: Although controlled laboratory experiments have been conducted to demonstrate the sensitivity of allergenic pollen production to future climatic change tie, increased CO2 and temperature), no in situ data are available. Objective: The purpose of this investigation was to assess, under realistic conditions, the impact of climatic change on pollen production of common ragweed, a ubiquitous weed occurring in disturbed sites and the principal source of pollen associated with seasonal allergenic rhinitis. Methods: We used an existing temperature/CO2 gradient between urban and rural areas to examine the quantitative and qualitative aspects of ragweed growth and pollen production. Results: For 2000 and 200 1, average daily (24-hour) values of CO2 concentration and air temperature within an urban environment were 30% to 31% and 1.8degrees to 2.0degreesC (3.4degrees to 3.6degreesF) higher than those at a rural site. This result is consistent with most global change scenarios. Ragweed grew faster, flowered earlier, and produced significantly greater above-ground biomass and ragweed pollen at urban locations than at rural locations. Conclusions: Here we show that 2 aspects of future global environmental change, air temperature and atmospheric CO2, are already significantly higher in urban relative to rural areas. In general, we show that regional urbanization-induced temperature/CO2 increases similar to those associated with projected global climatic change might already have public health consequences; we suggest that urbanization, per se, might provide a low-cost alternative to current experimental methods evaluating plant responses to climate change. (J Allergy Clin Immunol 2003;111:290-5.).	28	168	2003	6	10.1067/mai.2003.53	Allergy; Immunology
Gastrointestinal eosinophils. The gut-associated lymphoid tissue (GALT) is composed of lymphocytes residing in Peyer's patches, lamina propria, and intraepithelial compartments. In addition to these features which distinguish GALT from other peripheral sites of the immune system, the gastrointestinal immune system is also composed of resident eosinophils. Eosinophils are generally considered to be peripheral blood leukocytes that have an important proinflammatory role in various immune disorders. Although most research concerning this cell has focused on understanding its trafficking and function in the blood and lung, recent studies have also started to elucidate its regulation and function in the gastrointestinal tract. Interestingly, eosinophil numbers in the gastrointestinal tract are substantially higher than in other tissues. At baseline (healthy conditions), most eosinophils reside in the lamina propria in the stomach and intestine. Eosinophil homing to these sites occurs during embryonic development and their levels in perinatal mice are comparable to those in adults, indicating that their homing is not dependent upon the presence of intestinal flora. Furthermore, eosinophil localization to the lamina propria at baseline is critically regulated by eotaxin, a chemokine constitutively expressed throughout the gastrointestinal tract. Although eotaxin is required for eosinophil homing, its expression in the esophagus is not sufficient for eosinophil accumulation, since this organ is devoid of eosinophils at baseline. During Th2-associated inflammatory conditions (e.g. interleukin (IL)-5 overexpression or oral allergen challenge), marked increases of eosinophils occur not only in the lamina propria but also in Peyer's patches. The accumulation of Peyer's patch eosinophils, which mainly occurs in the outer cortex and interfollicular regions, is critically regulated by IL-5 and less significantly by eotaxin, suggesting the involvement of other eosinophil chemokines in this lymphoid compartment. Preliminary investigations have shown that gastrointestinal eosinophils express the alpha4 beta7 integrin and that this molecule is responsible, in part, for eosinophil homing. In summary, eosinophils are resident cells of the gastrointestinal immune system whose levels can be induced by antigen exposure under Th2 conditions, in a manner that is critically regulated by eotaxin and IL-5. We propose that eosinophils are integral members of the gastrointestinal immune system and are likely to be important in innate, regulatory and inflammatory immune responses.. major basic-protein| colony-stimulating factor| accumulation in-vivo| human cc-chemokine| airway hyperresponsiveness| gastroesophageal reflux| tissue eosinophilia| endothelial-cells| cationic protein| food allergy.	FEB-2001	major basic-protein| colony-stimulating factor| accumulation in-vivo| human cc-chemokine| airway hyperresponsiveness| gastroesophageal reflux| tissue eosinophilia| endothelial-cells| cationic protein| food allergy	Rothenberg, ME; Mishra, A; Brandt, EB; Hogan, SP	Gastrointestinal eosinophils		IMMUNOLOGICAL REVIEWS		MAJOR BASIC-PROTEIN; COLONY-STIMULATING FACTOR; ACCUMULATION IN-VIVO; HUMAN CC-CHEMOKINE; AIRWAY HYPERRESPONSIVENESS; GASTROESOPHAGEAL REFLUX; TISSUE EOSINOPHILIA; ENDOTHELIAL-CELLS; CATIONIC PROTEIN; FOOD ALLERGY	The gut-associated lymphoid tissue (GALT) is composed of lymphocytes residing in Peyer's patches, lamina propria, and intraepithelial compartments. In addition to these features which distinguish GALT from other peripheral sites of the immune system, the gastrointestinal immune system is also composed of resident eosinophils. Eosinophils are generally considered to be peripheral blood leukocytes that have an important proinflammatory role in various immune disorders. Although most research concerning this cell has focused on understanding its trafficking and function in the blood and lung, recent studies have also started to elucidate its regulation and function in the gastrointestinal tract. Interestingly, eosinophil numbers in the gastrointestinal tract are substantially higher than in other tissues. At baseline (healthy conditions), most eosinophils reside in the lamina propria in the stomach and intestine. Eosinophil homing to these sites occurs during embryonic development and their levels in perinatal mice are comparable to those in adults, indicating that their homing is not dependent upon the presence of intestinal flora. Furthermore, eosinophil localization to the lamina propria at baseline is critically regulated by eotaxin, a chemokine constitutively expressed throughout the gastrointestinal tract. Although eotaxin is required for eosinophil homing, its expression in the esophagus is not sufficient for eosinophil accumulation, since this organ is devoid of eosinophils at baseline. During Th2-associated inflammatory conditions (e.g. interleukin (IL)-5 overexpression or oral allergen challenge), marked increases of eosinophils occur not only in the lamina propria but also in Peyer's patches. The accumulation of Peyer's patch eosinophils, which mainly occurs in the outer cortex and interfollicular regions, is critically regulated by IL-5 and less significantly by eotaxin, suggesting the involvement of other eosinophil chemokines in this lymphoid compartment. Preliminary investigations have shown that gastrointestinal eosinophils express the alpha4 beta7 integrin and that this molecule is responsible, in part, for eosinophil homing. In summary, eosinophils are resident cells of the gastrointestinal immune system whose levels can be induced by antigen exposure under Th2 conditions, in a manner that is critically regulated by eotaxin and IL-5. We propose that eosinophils are integral members of the gastrointestinal immune system and are likely to be important in innate, regulatory and inflammatory immune responses.	130	168	2001	17	10.1034/j.1600-065X.2001.790114.x	Immunology
Oxidants and the pathogenesis of lung diseases. The increasing number of population-based and epiderniologic associations between oxidant pollutant exposures and cardiopulmonary disease exacerbation, decrements in pulmonary function, and mortality underscores the important detrimental effects of oxidants on public health. Because inhaled oxidants initiate a number of pathologic processes, including inflammation of the airways, which may contribute to the pathogenesis and/or exacerbation of airways disease, it is critical to understand the mechanisms through which exogenous and endogenous oxidants interact with molecules in the cells, tissues, and epithelial lining fluid of the lung. Furthermore, it is clear that interindividual variation in response to a given exposure also exists across an individual lifetime. Because of the potential impact that oxidant exposures may have on reproductive outcomes and infant, child, and adult health, identification of the intrinsic and extrinsic factors that may influence susceptibility to oxidants remains an important issue. In this review, we discuss mechanisms of oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and exacerbation (eg, asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome), and the potential risk factors (eg, age, genetics) for enhanced susceptibility to oxidant-induced disease.. oxidative stress| antioxidant| genetics| susceptibility| infant| reproductive outcome| premature| children| elderly| asthma| chronic obstructive pulmonary disease| ozone| pollutants| particulates| pm| acute respiratory distress syndrome| hyperoxia| snp| single nucleotide polymorphism|obstructive pulmonary-disease| respiratory-distress-syndrome| low-birth-weight| exhaled breath condensate| diesel exhaust particles| ambient air-pollution| surfactant protein-a| acute ozone exposure| lipid ozonation products| glutathione-s-transferase.	SEP-2008	oxidative stress| antioxidant| genetics| susceptibility| infant| reproductive outcome| premature| children| elderly| asthma| chronic obstructive pulmonary disease| ozone| pollutants| particulates| pm| acute respiratory distress syndrome| hyperoxia| snp| single nucleotide polymorphism|obstructive pulmonary-disease| respiratory-distress-syndrome| low-birth-weight| exhaled breath condensate| diesel exhaust particles| ambient air-pollution| surfactant protein-a| acute ozone exposure| lipid ozonation products| glutathione-s-transferase	Ciencewicki, J; Trivedi, S; Kleeberger, SR	Oxidants and the pathogenesis of lung diseases		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	oxidative stress; antioxidant; genetics; susceptibility; infant; reproductive outcome; premature; children; elderly; asthma; chronic obstructive pulmonary disease; ozone; pollutants; particulates; PM; acute respiratory distress syndrome; hyperoxia; SNP; single nucleotide polymorphism	OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY-DISTRESS-SYNDROME; LOW-BIRTH-WEIGHT; EXHALED BREATH CONDENSATE; DIESEL EXHAUST PARTICLES; AMBIENT AIR-POLLUTION; SURFACTANT PROTEIN-A; ACUTE OZONE EXPOSURE; LIPID OZONATION PRODUCTS; GLUTATHIONE-S-TRANSFERASE	The increasing number of population-based and epiderniologic associations between oxidant pollutant exposures and cardiopulmonary disease exacerbation, decrements in pulmonary function, and mortality underscores the important detrimental effects of oxidants on public health. Because inhaled oxidants initiate a number of pathologic processes, including inflammation of the airways, which may contribute to the pathogenesis and/or exacerbation of airways disease, it is critical to understand the mechanisms through which exogenous and endogenous oxidants interact with molecules in the cells, tissues, and epithelial lining fluid of the lung. Furthermore, it is clear that interindividual variation in response to a given exposure also exists across an individual lifetime. Because of the potential impact that oxidant exposures may have on reproductive outcomes and infant, child, and adult health, identification of the intrinsic and extrinsic factors that may influence susceptibility to oxidants remains an important issue. In this review, we discuss mechanisms of oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and exacerbation (eg, asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome), and the potential risk factors (eg, age, genetics) for enhanced susceptibility to oxidant-induced disease.	182	167	2008	13	10.1016/j.jaci.2008.08.004	Allergy; Immunology
Effects of ethanol (E85) versus gasoline vehicles on cancer and mortality in the United States. Ethanol use in vehicle fuel is increasing worldwide, but the potential cancer risk and ozone-related health consequences of a large-scale conversion from gasoline to ethanol have not been examined. Here, a nested global-through-urban air pollution/weather forecast model is combined with high-resolution future emission inventories, population data, and health effects data to examine the effect of converting from gasoline to E85 on cancer, mortality, and hospitalization in the United States as a whole and Los Angeles in particular. Under the base-case emission scenario derived, which accounted for projected improvements in gasoline and E85 vehicle emission controls, it was found that E85 (85% ethanol fuel, 15% gasoline) may increase ozone-related mortality, hospitalization, and asthma by about 9% in Los Angeles and 4% in the United States as a whole relative to 100% gasoline. Ozone increases in Los Angeles and the northeast were partially offset by decreases in the southeast. E85 also increased peroxyacetyl nitrate (PAN) in the U.S. but was estimated to cause little change in cancer risk. Due to its ozone effects, future E85 may be a greater overall public health risk than gasoline. However, because of the uncertainty in future emission regulations, it can be concluded with confidence only that E85 is unlikely to improve air quality over future gasoline vehicles. Unburned ethanol emissions from E85 may result in a global-scale source of acetaldehyde larger than that of direct emissions.. emissions| fuel| energy| air.	JUN 1-2007	emissions| fuel| energy| air	Jacobson, MZ	Effects of ethanol (E85) versus gasoline vehicles on cancer and mortality in the United States		ENVIRONMENTAL SCIENCE & TECHNOLOGY		EMISSIONS; FUEL; ENERGY; AIR	Ethanol use in vehicle fuel is increasing worldwide, but the potential cancer risk and ozone-related health consequences of a large-scale conversion from gasoline to ethanol have not been examined. Here, a nested global-through-urban air pollution/weather forecast model is combined with high-resolution future emission inventories, population data, and health effects data to examine the effect of converting from gasoline to E85 on cancer, mortality, and hospitalization in the United States as a whole and Los Angeles in particular. Under the base-case emission scenario derived, which accounted for projected improvements in gasoline and E85 vehicle emission controls, it was found that E85 (85% ethanol fuel, 15% gasoline) may increase ozone-related mortality, hospitalization, and asthma by about 9% in Los Angeles and 4% in the United States as a whole relative to 100% gasoline. Ozone increases in Los Angeles and the northeast were partially offset by decreases in the southeast. E85 also increased peroxyacetyl nitrate (PAN) in the U.S. but was estimated to cause little change in cancer risk. Due to its ozone effects, future E85 may be a greater overall public health risk than gasoline. However, because of the uncertainty in future emission regulations, it can be concluded with confidence only that E85 is unlikely to improve air quality over future gasoline vehicles. Unburned ethanol emissions from E85 may result in a global-scale source of acetaldehyde larger than that of direct emissions.	31	167	2007	8	10.1021/es062085v	Engineering; Environmental Sciences & Ecology
Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample. Study objectives: The fraction of exhaled nitric oxide (FENO) is elevated in subjects with asthma and atopy, and it has been proposed to be a noninvasive marker of airway inflammation. In addition to asthma and atopy, there is limited information about the determinants of FENO in a general population. Design: Cross-sectional. Setting: A random adult general population sample. Participants: A total of 2,200 subjects, 1, 111 women and 1,089 men, aged 25 to 75 years. Interventions: The subjects were examined with regard to FENO, pulmonary function, anthropometric variables, and blood samples for Ig E, and completed a respiratory questionnaire. The associations between different determinants and FENO were analyzed with multiple linear regression models. Results: The median value of FENO was 16.0 parts per billion (ppb), ranging from 2.4 to 199 ppb. Height, age, atopy, reporting of asthma symptoms in the last month, and reported use of inhaled steroids were positively associated with FENO. Current smokers had lower values of FENO. Gender was not associated with FENO. Conclusions: In this random adult population sample, height, but not gender, was associated with FENO. Furthermore, asthma symptoms in the last month, reported use of inhaled steroids, and atopy were positively and independently associated with FENO, while there was a negative association with smoking.. asthma| epidemiology| exhaled nitric oxide| gender|airway responsiveness| healthy-children| reference values| asthma| symptoms| smoking| sex| schoolchildren| community| exposure.	NOV-2006	asthma| epidemiology| exhaled nitric oxide| gender|airway responsiveness| healthy-children| reference values| asthma| symptoms| smoking| sex| schoolchildren| community| exposure	Olin, AC; Rosengren, A; Thelle, DS; Lissner, L; Bake, B; Toren, K	Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample		CHEST	asthma; epidemiology; exhaled nitric oxide; gender	AIRWAY RESPONSIVENESS; HEALTHY-CHILDREN; REFERENCE VALUES; ASTHMA; SYMPTOMS; SMOKING; SEX; SCHOOLCHILDREN; COMMUNITY; EXPOSURE	Study objectives: The fraction of exhaled nitric oxide (FENO) is elevated in subjects with asthma and atopy, and it has been proposed to be a noninvasive marker of airway inflammation. In addition to asthma and atopy, there is limited information about the determinants of FENO in a general population. Design: Cross-sectional. Setting: A random adult general population sample. Participants: A total of 2,200 subjects, 1, 111 women and 1,089 men, aged 25 to 75 years. Interventions: The subjects were examined with regard to FENO, pulmonary function, anthropometric variables, and blood samples for Ig E, and completed a respiratory questionnaire. The associations between different determinants and FENO were analyzed with multiple linear regression models. Results: The median value of FENO was 16.0 parts per billion (ppb), ranging from 2.4 to 199 ppb. Height, age, atopy, reporting of asthma symptoms in the last month, and reported use of inhaled steroids were positively associated with FENO. Current smokers had lower values of FENO. Gender was not associated with FENO. Conclusions: In this random adult population sample, height, but not gender, was associated with FENO. Furthermore, asthma symptoms in the last month, reported use of inhaled steroids, and atopy were positively and independently associated with FENO, while there was a negative association with smoking.	33	167	2006	7	10.1378/chest.130.5.1319	General & Internal Medicine; Respiratory System
Development of wheezing disorders and asthma in preschool children. Recent longitudinal studies have shed light on the pathogenesis and progression of asthma. The patterns of expression of childhood asthma that persist into adult life have been explored. Distinct asthma phenotypes (transient wheezing, nonatopic wheezing, and atopy-associated asthma) have been identified. Defining which children are at risk for persistent asthma could allow for better management and, potentially, for reduced morbidity and mortality.. asthma expression| phenotypes| wheezing| atopy|mid-adult life| childhood asthma| bronchial hyperresponsiveness| respiratory symptoms| lung-function| atopy| smoking| exposure| infants| disease.	FEB-2002	asthma expression| phenotypes| wheezing| atopy|mid-adult life| childhood asthma| bronchial hyperresponsiveness| respiratory symptoms| lung-function| atopy| smoking| exposure| infants| disease	Martinez, FD	Development of wheezing disorders and asthma in preschool children		PEDIATRICS	asthma expression; phenotypes; wheezing; atopy	MID-ADULT LIFE; CHILDHOOD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS; RESPIRATORY SYMPTOMS; LUNG-FUNCTION; ATOPY; SMOKING; EXPOSURE; INFANTS; DISEASE	Recent longitudinal studies have shed light on the pathogenesis and progression of asthma. The patterns of expression of childhood asthma that persist into adult life have been explored. Distinct asthma phenotypes (transient wheezing, nonatopic wheezing, and atopy-associated asthma) have been identified. Defining which children are at risk for persistent asthma could allow for better management and, potentially, for reduced morbidity and mortality.	26	167	2002	6		Pediatrics
Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. Background: Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial. Objective: We sought to investigate sustained efficacy I year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abello, Horsholm, Denmark). Methods: A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events. Results: Significant improvements in efficacy were consistently shown during 3 years' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and I year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified. Conclusion: Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained I year after treatment, which is indicative of disease modification and associated long-term benefits. (J Allergy Clin Immunol 2010;125:131-38.). allergy immunotherapy tablet| disease modification| grass pollen| immunotherapy| sublingual| sustained efficacy| rhinoconjunctivitis| placebo controlled| phleum pratense|6-year follow-up| house-dust mite| sublingual immunotherapy| immunological changes| controlled-trial| rhinitis| safety| children| performance| burden.	JAN-2010	allergy immunotherapy tablet| disease modification| grass pollen| immunotherapy| sublingual| sustained efficacy| rhinoconjunctivitis| placebo controlled| phleum pratense|6-year follow-up| house-dust mite| sublingual immunotherapy| immunological changes| controlled-trial| rhinitis| safety| children| performance| burden	Durham, SR; Emminger, W; Kapp, A; Colombo, G; de Monchy, JGR; Rak, S; Scadding, GK; Andersen, JS; Riis, B; Dahl, R	Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergy immunotherapy tablet; disease modification; grass pollen; immunotherapy; sublingual; sustained efficacy; rhinoconjunctivitis; placebo controlled; Phleum pratense	6-YEAR FOLLOW-UP; HOUSE-DUST MITE; SUBLINGUAL IMMUNOTHERAPY; IMMUNOLOGICAL CHANGES; CONTROLLED-TRIAL; RHINITIS; SAFETY; CHILDREN; PERFORMANCE; BURDEN	Background: Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial. Objective: We sought to investigate sustained efficacy I year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abello, Horsholm, Denmark). Methods: A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events. Results: Significant improvements in efficacy were consistently shown during 3 years' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and I year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified. Conclusion: Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained I year after treatment, which is indicative of disease modification and associated long-term benefits. (J Allergy Clin Immunol 2010;125:131-38.)	39	166	2010	8	10.1016/j.jaci.2009.10.035	Allergy; Immunology
Indoor residential chemical emissions as risk factors for-respiratory and allergic effects in children: a review. Most research into effects of residential exposures on respiratory health has focused on allergens, moisture/mold, endotoxin, or combustion products. A growing body of research from outside the US; however, has associated chemical emissions from common indoor materials with risk of asthma, allergies, and pulmonary infections. This review summarizes 21 studies in the epidemiologic literature on associations between indoor residential chemical emissions, or emission-related materials or activities, and respiratory health or allergy in infants or children. Associations, some strong, were reported between many risk factors and respiratory or allergic effects. Risk factors identified most frequently included formaldehyde or particleboard, phthalates or plastic materials, and recent painting. Findings for other risk factors, such as aromatic and aliphatic chemical compounds, were limited but suggestive. Elevated risks were also reported for renovation and cleaning activities, new furniture, and carpets or textile wallpaper. Reviewed studies were entirely observational, limited in size, and variable in quality, and specific risk factors identified may only be indicators for correlated, truly causal exposures. Nevertheless, overall evidence suggests a new class of residential risk factors for adverse respiratory effects, ubiquitous in modern residences, and distinct from those currently recognized. It is important to confirm and quantify any risks, to motivate and guide necessary preventive actions.. volatile organic-compounds| interior surface materials| peak expiratory flow| 3.0 ppm formaldehyde| young-children| house-dust| asthma symptoms| airway symptoms| mite allergen| building characteristics.	AUG-2007	volatile organic-compounds| interior surface materials| peak expiratory flow| 3.0 ppm formaldehyde| young-children| house-dust| asthma symptoms| airway symptoms| mite allergen| building characteristics	Mendell, MJ	Indoor residential chemical emissions as risk factors for-respiratory and allergic effects in children: a review		INDOOR AIR		VOLATILE ORGANIC-COMPOUNDS; INTERIOR SURFACE MATERIALS; PEAK EXPIRATORY FLOW; 3.0 PPM FORMALDEHYDE; YOUNG-CHILDREN; HOUSE-DUST; ASTHMA SYMPTOMS; AIRWAY SYMPTOMS; MITE ALLERGEN; BUILDING CHARACTERISTICS	Most research into effects of residential exposures on respiratory health has focused on allergens, moisture/mold, endotoxin, or combustion products. A growing body of research from outside the US; however, has associated chemical emissions from common indoor materials with risk of asthma, allergies, and pulmonary infections. This review summarizes 21 studies in the epidemiologic literature on associations between indoor residential chemical emissions, or emission-related materials or activities, and respiratory health or allergy in infants or children. Associations, some strong, were reported between many risk factors and respiratory or allergic effects. Risk factors identified most frequently included formaldehyde or particleboard, phthalates or plastic materials, and recent painting. Findings for other risk factors, such as aromatic and aliphatic chemical compounds, were limited but suggestive. Elevated risks were also reported for renovation and cleaning activities, new furniture, and carpets or textile wallpaper. Reviewed studies were entirely observational, limited in size, and variable in quality, and specific risk factors identified may only be indicators for correlated, truly causal exposures. Nevertheless, overall evidence suggests a new class of residential risk factors for adverse respiratory effects, ubiquitous in modern residences, and distinct from those currently recognized. It is important to confirm and quantify any risks, to motivate and guide necessary preventive actions.	103	166	2007	19	10.1111/j.1600-0668.2007.00478.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. Background: Pegylated liposomal doxorubicin (Doxil(R)) has been reported to cause immediate hypersensitivity reactions (HSRs) that cannot be explained as IgE-mediated (type I) allergy. Previous in vitro and animal studies indicated that activation of the complement (C) system might play a causal role in the process, a proposal that has not been tested in humans to date. Patients and methods: Patients with solid tumors (n=29) treated for the first time with Doxil were evaluated for HSRs and concurrent C activation. HSRs were classified from mild to severe, while C activation was estimated by serial measurement of plasma C terminal complex (SC5b-9) levels. Increases in SC5b-9 were compared in patients with or without reactions, and were correlated with Doxil dose rate. Results: Moderate to severe HSRs occurred in 45% of patients. Plasma SC5b-9 at 10 min after infusion was significantly elevated in 92% of reactor patients versus 56% in the non-reactor group, and the rise was greater in reactors than in non-reactors. We found significant association between C activation and HSRs, both showing direct correlation with the initial Doxil dose rate. Conclusions: C activation may play a key role in HSRs to Doxil. However, low-level C activation does not necessarily entail clinical symptoms, highlighting the probable involvement of further, as yet unidentified, amplification factors.. allergy| anaphylatoxins| cancer chemotherapy| doxorubicin| liposomes| hypersensitivity reactions|phase-ii| antitumor-activity| ovarian-cancer| chemotherapy| pharmacokinetics| paclitaxel| mechanism| toxicity| disease.	SEP-2003	allergy| anaphylatoxins| cancer chemotherapy| doxorubicin| liposomes| hypersensitivity reactions|phase-ii| antitumor-activity| ovarian-cancer| chemotherapy| pharmacokinetics| paclitaxel| mechanism| toxicity| disease	Chanan-Khan, A; Szebeni, J; Savay, S; Liebes, L; Rafique, NM; Alving, CR; Muggia, FM	Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions		ANNALS OF ONCOLOGY	allergy; anaphylatoxins; cancer chemotherapy; doxorubicin; liposomes; hypersensitivity reactions	PHASE-II; ANTITUMOR-ACTIVITY; OVARIAN-CANCER; CHEMOTHERAPY; PHARMACOKINETICS; PACLITAXEL; MECHANISM; TOXICITY; DISEASE	Background: Pegylated liposomal doxorubicin (Doxil(R)) has been reported to cause immediate hypersensitivity reactions (HSRs) that cannot be explained as IgE-mediated (type I) allergy. Previous in vitro and animal studies indicated that activation of the complement (C) system might play a causal role in the process, a proposal that has not been tested in humans to date. Patients and methods: Patients with solid tumors (n=29) treated for the first time with Doxil were evaluated for HSRs and concurrent C activation. HSRs were classified from mild to severe, while C activation was estimated by serial measurement of plasma C terminal complex (SC5b-9) levels. Increases in SC5b-9 were compared in patients with or without reactions, and were correlated with Doxil dose rate. Results: Moderate to severe HSRs occurred in 45% of patients. Plasma SC5b-9 at 10 min after infusion was significantly elevated in 92% of reactor patients versus 56% in the non-reactor group, and the rise was greater in reactors than in non-reactors. We found significant association between C activation and HSRs, both showing direct correlation with the initial Doxil dose rate. Conclusions: C activation may play a key role in HSRs to Doxil. However, low-level C activation does not necessarily entail clinical symptoms, highlighting the probable involvement of further, as yet unidentified, amplification factors.	29	166	2003	8	10.1093/annonc/mdg374	Oncology
New concepts in chronic obstructive pulmonary disease. Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability but has only recently been explored from a cellular and molecular perspective. In COPD, chronic inflammation leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterized by increased numbers of alveolar macrophages, neutrophils, and cytotoxic T lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). There is also a high level of oxidative stress, which may amplify this inflammation. There is increased elastolysis and probable involvement of matrix metalloproteinases. The inflammation and proteolysis in COPD is an amplification of the normal inflammatory response to cigarette smoke. Unlike asthma, this inflammation appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.. emphysema| bronchitis| inflammation| proteases| macrophage|randomized controlled trial| bronchoalveolar lavage fluid| sputum inflammatory markers| cystic-fibrosis sputum| exhaled nitric-oxide| air-flow limitation| chronic-bronchitis| alveolar macrophages| lung-function| inhaled budesonide.	2003	emphysema| bronchitis| inflammation| proteases| macrophage|randomized controlled trial| bronchoalveolar lavage fluid| sputum inflammatory markers| cystic-fibrosis sputum| exhaled nitric-oxide| air-flow limitation| chronic-bronchitis| alveolar macrophages| lung-function| inhaled budesonide	Barnes, PJ	New concepts in chronic obstructive pulmonary disease		ANNUAL REVIEW OF MEDICINE-SELECTED TOPICS IN THE CLINICAL SCIENCES	emphysema; bronchitis; inflammation; proteases; macrophage	RANDOMIZED CONTROLLED TRIAL; BRONCHOALVEOLAR LAVAGE FLUID; SPUTUM INFLAMMATORY MARKERS; CYSTIC-FIBROSIS SPUTUM; EXHALED NITRIC-OXIDE; AIR-FLOW LIMITATION; CHRONIC-BRONCHITIS; ALVEOLAR MACROPHAGES; LUNG-FUNCTION; INHALED BUDESONIDE	Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability but has only recently been explored from a cellular and molecular perspective. In COPD, chronic inflammation leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This is characterized by increased numbers of alveolar macrophages, neutrophils, and cytotoxic T lymphocytes, and the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). There is also a high level of oxidative stress, which may amplify this inflammation. There is increased elastolysis and probable involvement of matrix metalloproteinases. The inflammation and proteolysis in COPD is an amplification of the normal inflammatory response to cigarette smoke. Unlike asthma, this inflammation appears to be resistant to corticosteroids, prompting a search for novel anti-inflammatory therapies that may prevent the relentless progression of the disease.	103	166	2003	17	10.1146/annurev.med.54.101601.152209	General & Internal Medicine
Biomarkers of some pulmonary diseases in exhaled breath. Analysis of various biomarkers in exhaled breath allows completely non-invasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic firbrosis (CF), bronchiectasis and interstitial lung diseases. The technique is simple to perform, may be repeated frequently, and can be applied to children, including neonates, and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, ammonia), and many non-volatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate. Exhaled breath analysis may be used to quantify inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the monitoring of therapy. Most progress has been made with exhaled nitric oxide (NO), which is increased in atopic asthma, is correlated with other inflammatory indices and is reduced by treatment with corticosteroids and antileukotrienes, but not (beta (2)-agonists. In contrast, exhaled NO is normal in COPD, reduced in CF and diagnostically low in primary ciliary dyskinesia. Exhaled carbon monoxide (CO) is increased in asthma, COPD and CF. Increased concentrations of 8-isoprostane, hydrogen peroxide, nitrite and 3-nitrotyrosine are found in exhaled breath condensate in inflammatory lung diseases. Furthermore, increased levels of lipid mediators are found in these diseases, with a differential pattern depending on the nature of the disease process. In the future it is likely that smaller and more sensitive analysers will extend the discriminatory value of exhaled breath analysis and that these techniques may be available to diagnose and monitor respiratory diseases in the general practice and home setting.. airway inflammation| oxidative stress| nitric oxide| carbon monoxide| exhaled breath condensate| non-invasive markers| asthma| chronic obstructive pulmonary disease| cystic fibrosis| bronchiectasis| interstitial lung diseases| hydrogen peroxide| eicosanoids| products of lipid peroxidation| proteins| cytokines|nitric-oxide synthase| increased carbon-monoxide| respiratory-distress syndrome| leukotriene receptor antagonist| kappa-b activation| cystic-fibrosis| asthmatic-patients| hydrogen-peroxide| oxidative stress| airway inflammation.	JAN-FEB-2002	airway inflammation| oxidative stress| nitric oxide| carbon monoxide| exhaled breath condensate| non-invasive markers| asthma| chronic obstructive pulmonary disease| cystic fibrosis| bronchiectasis| interstitial lung diseases| hydrogen peroxide| eicosanoids| products of lipid peroxidation| proteins| cytokines|nitric-oxide synthase| increased carbon-monoxide| respiratory-distress syndrome| leukotriene receptor antagonist| kappa-b activation| cystic-fibrosis| asthmatic-patients| hydrogen-peroxide| oxidative stress| airway inflammation	Kharitonov, SA; Barnes, PJ	Biomarkers of some pulmonary diseases in exhaled breath		BIOMARKERS	airway inflammation; oxidative stress; nitric oxide; carbon monoxide; exhaled breath condensate; non-invasive markers; asthma; chronic obstructive pulmonary disease; cystic fibrosis; bronchiectasis; interstitial lung diseases; hydrogen peroxide; eicosanoids; products of lipid peroxidation; proteins; cytokines	NITRIC-OXIDE SYNTHASE; INCREASED CARBON-MONOXIDE; RESPIRATORY-DISTRESS SYNDROME; LEUKOTRIENE RECEPTOR ANTAGONIST; KAPPA-B ACTIVATION; CYSTIC-FIBROSIS; ASTHMATIC-PATIENTS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; AIRWAY INFLAMMATION	Analysis of various biomarkers in exhaled breath allows completely non-invasive monitoring of inflammation and oxidative stress in the respiratory tract in inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic firbrosis (CF), bronchiectasis and interstitial lung diseases. The technique is simple to perform, may be repeated frequently, and can be applied to children, including neonates, and patients with severe disease in whom more invasive procedures are not possible. Several volatile chemicals can be measured in the breath (nitric oxide, carbon monoxide, ammonia), and many non-volatile molecules (mediators, oxidation and nitration products, proteins) may be measured in exhaled breath condensate. Exhaled breath analysis may be used to quantify inflammation and oxidative stress in the respiratory tract, in differential diagnosis of airway disease and in the monitoring of therapy. Most progress has been made with exhaled nitric oxide (NO), which is increased in atopic asthma, is correlated with other inflammatory indices and is reduced by treatment with corticosteroids and antileukotrienes, but not (beta (2)-agonists. In contrast, exhaled NO is normal in COPD, reduced in CF and diagnostically low in primary ciliary dyskinesia. Exhaled carbon monoxide (CO) is increased in asthma, COPD and CF. Increased concentrations of 8-isoprostane, hydrogen peroxide, nitrite and 3-nitrotyrosine are found in exhaled breath condensate in inflammatory lung diseases. Furthermore, increased levels of lipid mediators are found in these diseases, with a differential pattern depending on the nature of the disease process. In the future it is likely that smaller and more sensitive analysers will extend the discriminatory value of exhaled breath analysis and that these techniques may be available to diagnose and monitor respiratory diseases in the general practice and home setting.	217	166	2002	32	10.1080/13547500110104233	Biotechnology & Applied Microbiology; Toxicology
The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus. Background There have been only a few studies of how allergens cross the airway epithelium to cause allergic sensitization. House dust mite fecal pellets (HDMFP) contain several proteolytic enzymes. Group I allergens are cysteine peptidases, whilst those of groups 3, 6 and 9 have catalytic sites indicative of enzymes that mechanistically behave as serine peptidases. We have previously shown that the group 1 allergen Der p 1 leads to cleavage of tight junctions (TJs), allowing allergen delivery to antigen presenting cells. Objective In this study we determined whether HDMFP serine peptidases similarly compromise the airway epithelium by attacking TJs, desmosomes and adherens junctions. Methods Experiments were performed in monolayers of MDCK, Calu-3 or 16HBE14o-epithelial cells. Cell junction morphology was examined by 2-photon molecular excitation microscopy and digital image analysis. Barrier function was measured as mannitol permeability. Cleavage of cell adhesion proteins was studied by immunoblotting and mass spectrometry. Results HDMFP serine peptidases led to a progressive cleavage of TJs and increased epithelial permeability. Desmosomal puncta became more concentrated. Cleavage of TJs involved proteolysis of the TJ proteins, occludin and ZO-1. This was associated with activation of intracellular proteolysis of ZO-1. In contrast to occludin, E-cadherin of adherens junctions was cleaved less extensively. Although Calu-3 and 16HBE14o-cells expressed tethered ligand receptors for serine peptidases, these were not responsible for transducing the changes in TJs. Conclusion HDMFP serine peptidases cause cleavage of TJs. This study identifies a second general class of HDM peptidase capable of increasing epithelial permeability and thereby creating conditions that would favour transepithelial delivery of allergens.. asthma| house dust mite allergens| tight junctions| serine peptidases| adherens junctions| allergic sensitization| occludin| claudins|house-dust mite| der-p-i| membrane-proteins| allergen| permeability| asthma| childhood| cleavage| receptor| der-p-1.	FEB-2001	asthma| house dust mite allergens| tight junctions| serine peptidases| adherens junctions| allergic sensitization| occludin| claudins|house-dust mite| der-p-i| membrane-proteins| allergen| permeability| asthma| childhood| cleavage| receptor| der-p-1	Wan, H; Winton, HL; Soeller, C; Taylor, GW; Gruenert, DC; Thompson, PJ; Cannell, MB; Stewart, GA; Garrod, DR; Robinson, C	The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; house dust mite allergens; tight junctions; serine peptidases; adherens junctions; allergic sensitization; occludin; claudins	HOUSE-DUST MITE; DER-P-I; MEMBRANE-PROTEINS; ALLERGEN; PERMEABILITY; ASTHMA; CHILDHOOD; CLEAVAGE; RECEPTOR; DER-P-1	Background There have been only a few studies of how allergens cross the airway epithelium to cause allergic sensitization. House dust mite fecal pellets (HDMFP) contain several proteolytic enzymes. Group I allergens are cysteine peptidases, whilst those of groups 3, 6 and 9 have catalytic sites indicative of enzymes that mechanistically behave as serine peptidases. We have previously shown that the group 1 allergen Der p 1 leads to cleavage of tight junctions (TJs), allowing allergen delivery to antigen presenting cells. Objective In this study we determined whether HDMFP serine peptidases similarly compromise the airway epithelium by attacking TJs, desmosomes and adherens junctions. Methods Experiments were performed in monolayers of MDCK, Calu-3 or 16HBE14o-epithelial cells. Cell junction morphology was examined by 2-photon molecular excitation microscopy and digital image analysis. Barrier function was measured as mannitol permeability. Cleavage of cell adhesion proteins was studied by immunoblotting and mass spectrometry. Results HDMFP serine peptidases led to a progressive cleavage of TJs and increased epithelial permeability. Desmosomal puncta became more concentrated. Cleavage of TJs involved proteolysis of the TJ proteins, occludin and ZO-1. This was associated with activation of intracellular proteolysis of ZO-1. In contrast to occludin, E-cadherin of adherens junctions was cleaved less extensively. Although Calu-3 and 16HBE14o-cells expressed tethered ligand receptors for serine peptidases, these were not responsible for transducing the changes in TJs. Conclusion HDMFP serine peptidases cause cleavage of TJs. This study identifies a second general class of HDM peptidase capable of increasing epithelial permeability and thereby creating conditions that would favour transepithelial delivery of allergens.	37	166	2001	16	10.1046/j.1365-2222.2001.00970.x	Allergy; Immunology
Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. Bankground in December, 2007, family cluster of two individuals infected with highly pathogenic avian influenza A (H5N1) virus was identified in Jiangsu Province, China. Field and laboratory investigations were implemented immediately by public-health authorities. Methods Epidemiological, clinical, and virological data were collected and analysed. Respiratory specimens from the patients were tested by reverse transcriptase (RT) PCR and by viral culture for the presence of H5N1 virus. Contacts of cases were monitored for symptoms of illness for 10 days. Any contacts who became ill had respiratory specimens collected for H5N1 testing by RT PCR. Sera were obtained from contacts for H5N1 serological testing by microneutralisation and horse red-blood-cell haemagglutinin inhibition assays. Findings The 24-year-old index case died, and the second case, his 52-year-old father, survived after receiving early antiviral treatment and post-vaccination plasma from a participant in an H5N1 vaccine trial. The index case's only plausible exposure to H5N1 virus was a poultry market visit 6 days before the onset of illness. The second case had substantial unprotected close exposure to his ill son. 91 contacts with close exposure to one or both cases without adequate protective equipment provided consent for serological investigation. Of these individuals, 78 (86%) received oseltamivir chemoprophylaxis and two had mild illness. Both ill contacts tested negative for H5N1 by RT PCR. All 91 close contacts tested negative for H5N1 antibodies. HSN1 viruses isolated from the two cases were genetically identical except for one non-synonymous nucleotide substitution. Interpretation Limited, non-sustained person-to-person transmission of H5N1 virus probably occurred in this family cluster. Funding Chinese Ministry of Science and Technology; US National Institute of Allergy and infectious Diseases, National Institutes of Health; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases.. health-care workers| receptor specificity| anti-h5 antibody| hong-kong| infection| hemagglutinin| disease| epidemiology| risk.	APR-MAY-2008	health-care workers| receptor specificity| anti-h5 antibody| hong-kong| infection| hemagglutinin| disease| epidemiology| risk	Wang, H; Feng, Z; Shu, Y; Yu, H; Zhou, L; Zu, RQ; Huai, Y; Dong, J; Bao, CJ; Wen, LY; Wang, H; Yang, P; Zhao, W; Dong, LB; Zhou, MH; Liao, QH; Yang, HT; Wang, M; Lu, XJ; Shi, ZY; Wang, W; Gu, L; Zhu, FC; Li, Q; Yin, WD; Yang, WZ; Li, DX; Uyeki, TM; Wang, Y	Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China		LANCET		HEALTH-CARE WORKERS; RECEPTOR SPECIFICITY; ANTI-H5 ANTIBODY; HONG-KONG; INFECTION; HEMAGGLUTININ; DISEASE; EPIDEMIOLOGY; RISK	Bankground in December, 2007, family cluster of two individuals infected with highly pathogenic avian influenza A (H5N1) virus was identified in Jiangsu Province, China. Field and laboratory investigations were implemented immediately by public-health authorities. Methods Epidemiological, clinical, and virological data were collected and analysed. Respiratory specimens from the patients were tested by reverse transcriptase (RT) PCR and by viral culture for the presence of H5N1 virus. Contacts of cases were monitored for symptoms of illness for 10 days. Any contacts who became ill had respiratory specimens collected for H5N1 testing by RT PCR. Sera were obtained from contacts for H5N1 serological testing by microneutralisation and horse red-blood-cell haemagglutinin inhibition assays. Findings The 24-year-old index case died, and the second case, his 52-year-old father, survived after receiving early antiviral treatment and post-vaccination plasma from a participant in an H5N1 vaccine trial. The index case's only plausible exposure to H5N1 virus was a poultry market visit 6 days before the onset of illness. The second case had substantial unprotected close exposure to his ill son. 91 contacts with close exposure to one or both cases without adequate protective equipment provided consent for serological investigation. Of these individuals, 78 (86%) received oseltamivir chemoprophylaxis and two had mild illness. Both ill contacts tested negative for H5N1 by RT PCR. All 91 close contacts tested negative for H5N1 antibodies. HSN1 viruses isolated from the two cases were genetically identical except for one non-synonymous nucleotide substitution. Interpretation Limited, non-sustained person-to-person transmission of H5N1 virus probably occurred in this family cluster. Funding Chinese Ministry of Science and Technology; US National Institute of Allergy and infectious Diseases, National Institutes of Health; China-US Collaborative Program on Emerging and Re-emerging Infectious Diseases.	39	165	2008	8	10.1016/S0140-6736(08)60493-6	General & Internal Medicine
The effect of telithromycin in acute exacerbations of asthma. BACKGROUND: We conducted a double-blind, randomized, placebo-controlled study to evaluate the efficacy of telithromycin in patients with acute exacerbations of asthma. METHODS: A total of 278 adults with diagnosed asthma were enrolled within 24 hours after an acute exacerbation of asthma requiring short-term medical care. The patients were randomly assigned to receive 10 days of oral treatment with telithromycin (at a dose of 800 mg daily) or placebo in addition to usual care. Primary efficacy end points were a change from baseline over the treatment period in symptoms (as recorded by patients in a diary card) and in the peak expiratory flow in the morning at home. The presence of Chlamydophila pneumoniae or Mycoplasma pneumoniae was ascertained by serologic analysis, polymerase chain reaction, and culture. RESULTS: Of the two prespecified primary outcomes, only asthma symptoms showed a significantly greater reduction among patients receiving telithromycin than among those receiving placebo. Mean (+/-SD) scores on a test of asthma symptoms (on a 7-point scale, with 0 denoting no symptoms and 6 denoting severe symptoms) were 3.0+/-1.4 at baseline and 1.7+/-1.1 at the end of treatment for the telithromycin group and 2.8+/-1.3 at baseline and 2.0+/-1.0 at the end of treatment for the placebo group. The mean decrease in symptom scores during the treatment period was 1.3 for telithromycin and 1.0 for placebo (mean difference, -0.3; 95 percent confidence interval, -0.5 to -0.1; P=0.004). There was no significant treatment effect on the other primary outcome measure, a change in morning peak expiratory flow. Nausea was more common among patients in the telithromycin group than in the placebo group (P=0.01). Although 61 percent of patients had evidence of infection with C. pneumoniae, M. pneumoniae, or both, there was no relationship between bacteriologic status and the response to asthma treatment. CONCLUSIONS: This study provides evidence of the benefit of telithromycin in patients with acute exacerbations of asthma; the mechanisms of benefit remain unclear.. in-vitro activity| mycoplasma-pneumoniae| chlamydia-pneumoniae| hmr 3647| ketolide| infection| trial.	APR 13-2006	in-vitro activity| mycoplasma-pneumoniae| chlamydia-pneumoniae| hmr 3647| ketolide| infection| trial	Johnston, SL; Blasi, F; Black, PN; Martin, RJ; Farrell, DJ; Nieman, RB	The effect of telithromycin in acute exacerbations of asthma		NEW ENGLAND JOURNAL OF MEDICINE		IN-VITRO ACTIVITY; MYCOPLASMA-PNEUMONIAE; CHLAMYDIA-PNEUMONIAE; HMR 3647; KETOLIDE; INFECTION; TRIAL	BACKGROUND: We conducted a double-blind, randomized, placebo-controlled study to evaluate the efficacy of telithromycin in patients with acute exacerbations of asthma. METHODS: A total of 278 adults with diagnosed asthma were enrolled within 24 hours after an acute exacerbation of asthma requiring short-term medical care. The patients were randomly assigned to receive 10 days of oral treatment with telithromycin (at a dose of 800 mg daily) or placebo in addition to usual care. Primary efficacy end points were a change from baseline over the treatment period in symptoms (as recorded by patients in a diary card) and in the peak expiratory flow in the morning at home. The presence of Chlamydophila pneumoniae or Mycoplasma pneumoniae was ascertained by serologic analysis, polymerase chain reaction, and culture. RESULTS: Of the two prespecified primary outcomes, only asthma symptoms showed a significantly greater reduction among patients receiving telithromycin than among those receiving placebo. Mean (+/-SD) scores on a test of asthma symptoms (on a 7-point scale, with 0 denoting no symptoms and 6 denoting severe symptoms) were 3.0+/-1.4 at baseline and 1.7+/-1.1 at the end of treatment for the telithromycin group and 2.8+/-1.3 at baseline and 2.0+/-1.0 at the end of treatment for the placebo group. The mean decrease in symptom scores during the treatment period was 1.3 for telithromycin and 1.0 for placebo (mean difference, -0.3; 95 percent confidence interval, -0.5 to -0.1; P=0.004). There was no significant treatment effect on the other primary outcome measure, a change in morning peak expiratory flow. Nausea was more common among patients in the telithromycin group than in the placebo group (P=0.01). Although 61 percent of patients had evidence of infection with C. pneumoniae, M. pneumoniae, or both, there was no relationship between bacteriologic status and the response to asthma treatment. CONCLUSIONS: This study provides evidence of the benefit of telithromycin in patients with acute exacerbations of asthma; the mechanisms of benefit remain unclear.	23	165	2006	12	10.1056/NEJMoa044080	General & Internal Medicine
Creating healthy communities, healthy homes, healthy people: Initiating a research agenda on the built environment and public health. Mounting evidence suggests physical and mental health problems relate to the built environment, including human-modified places such as homes, schools, workplaces, parks, industrial areas, farms, roads and highways. The public health relevance of the built environment requires examination. Preliminary research demonstrates the health benefits of sustainable communities. However, the impact of mediating and moderating factors within the built environment on health must be explored further. Given the complexity of the built environment, understanding its influence on human health requires a community-based, multilevel, interdisciplinary research approach. The authors offer recommendations, based upon a recent conference sponsored by the National Institute of Environmental Health Sciences (NIEHS), for research and policy approaches, and suggest interagency research alliances for greater public health impact.. physical-activity| united-states| children| population| cockroach| asthma| risk| city.	SEP-2003	physical-activity| united-states| children| population| cockroach| asthma| risk| city	Srinivasan, S; O'Fallon, LR; Dearry, A	Creating healthy communities, healthy homes, healthy people: Initiating a research agenda on the built environment and public health		AMERICAN JOURNAL OF PUBLIC HEALTH		PHYSICAL-ACTIVITY; UNITED-STATES; CHILDREN; POPULATION; COCKROACH; ASTHMA; RISK; CITY	Mounting evidence suggests physical and mental health problems relate to the built environment, including human-modified places such as homes, schools, workplaces, parks, industrial areas, farms, roads and highways. The public health relevance of the built environment requires examination. Preliminary research demonstrates the health benefits of sustainable communities. However, the impact of mediating and moderating factors within the built environment on health must be explored further. Given the complexity of the built environment, understanding its influence on human health requires a community-based, multilevel, interdisciplinary research approach. The authors offer recommendations, based upon a recent conference sponsored by the National Institute of Environmental Health Sciences (NIEHS), for research and policy approaches, and suggest interagency research alliances for greater public health impact.	51	165	2003	5	10.2105/AJPH.93.9.1446	Public, Environmental & Occupational Health
Beyond Atopy Multiple Patterns of Sensitization in Relation to Asthma in a Birth Cohort Study. Rationale: The pattern of IgE response (over time or to specific allergens) may reflect different atopic vulnerabilities which are related to the presence of asthma in a fundamentally different way from current definition of atopy. Objectives: To redefine the atopic phenotype by identifying latent structure within a complex dataset, taking into account the timing and type of sensitization to specific allergens, and relating these novel phenotypes to asthma. Methods: In a population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood, we used a machine learning approach to cluster children into multiple atopic classes in an unsupervised way. We then investigated the relation between these classes and asthma (symptoms, hospitalizations, lung function and airway reactivity). Measurements and Main Results: A five-class model indicated a complex latent structure, in which children with atopic vulnerability were clustered into four distinct classes (Multiple Early [112/1053, 10.6%]; Multiple Late [171/1053, 16.2%]; Dust Mite [47/1053,4.5%]; and Non-dust Mite [100/1053, 9.5%]), with a fifth class describing children with No Latent Vulnerability (623/1053, 59.2%). The association with asthma was considerably stronger for Multiple Early compared with other classes and conventionally defined atopy (odds ratio [95% Cl]: 29.3 [11.1-77.2] versus 12.4 [4.8-32.2] versus 11.6 [4.8-27.9] for Multiple Early class versus Ever Atopic versus Atopic age 8). Lung function and airway reactivity were significantly poorer among children in Multiple Early class. Cox regression demonstrated a highly significant increase in risk of hospital admissions for wheeze/asthma after age 3 yr only among children in the Multiple Early class (HR 9.2 [3.5-24.0], P < 0.001). Conclusions: IgE antibody responses do not reflect a single phenotype of atopy, but several different atopic vulnerabilities which differ in their relation with asthma presence and severity.. asthma| atopy| unsupervised clustering| bayesian inference| machine learning in epidemiology|age 3 years| lung-function| respiratory symptoms| revised nomenclature| preschool-children| manchester asthma| early-life| allergy| childhood| prevalence.	JUN 1-2010	asthma| atopy| unsupervised clustering| bayesian inference| machine learning in epidemiology|age 3 years| lung-function| respiratory symptoms| revised nomenclature| preschool-children| manchester asthma| early-life| allergy| childhood| prevalence	Simpson, A; Tan, VYF; Winn, J; Svensen, M; Bishop, CM; Heckerman, DE; Buchan, I; Custovic, A	Beyond Atopy Multiple Patterns of Sensitization in Relation to Asthma in a Birth Cohort Study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; atopy; unsupervised clustering; Bayesian inference; machine learning in epidemiology	AGE 3 YEARS; LUNG-FUNCTION; RESPIRATORY SYMPTOMS; REVISED NOMENCLATURE; PRESCHOOL-CHILDREN; MANCHESTER ASTHMA; EARLY-LIFE; ALLERGY; CHILDHOOD; PREVALENCE	Rationale: The pattern of IgE response (over time or to specific allergens) may reflect different atopic vulnerabilities which are related to the presence of asthma in a fundamentally different way from current definition of atopy. Objectives: To redefine the atopic phenotype by identifying latent structure within a complex dataset, taking into account the timing and type of sensitization to specific allergens, and relating these novel phenotypes to asthma. Methods: In a population-based birth cohort in which multiple skin and IgE tests have been taken throughout childhood, we used a machine learning approach to cluster children into multiple atopic classes in an unsupervised way. We then investigated the relation between these classes and asthma (symptoms, hospitalizations, lung function and airway reactivity). Measurements and Main Results: A five-class model indicated a complex latent structure, in which children with atopic vulnerability were clustered into four distinct classes (Multiple Early [112/1053, 10.6%]; Multiple Late [171/1053, 16.2%]; Dust Mite [47/1053,4.5%]; and Non-dust Mite [100/1053, 9.5%]), with a fifth class describing children with No Latent Vulnerability (623/1053, 59.2%). The association with asthma was considerably stronger for Multiple Early compared with other classes and conventionally defined atopy (odds ratio [95% Cl]: 29.3 [11.1-77.2] versus 12.4 [4.8-32.2] versus 11.6 [4.8-27.9] for Multiple Early class versus Ever Atopic versus Atopic age 8). Lung function and airway reactivity were significantly poorer among children in Multiple Early class. Cox regression demonstrated a highly significant increase in risk of hospital admissions for wheeze/asthma after age 3 yr only among children in the Multiple Early class (HR 9.2 [3.5-24.0], P < 0.001). Conclusions: IgE antibody responses do not reflect a single phenotype of atopy, but several different atopic vulnerabilities which differ in their relation with asthma presence and severity.	35	164	2010	7	10.1164/rccm.200907-1101OC	General & Internal Medicine; Respiratory System
Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age. Background: Recent studies have documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with rhinitis, but the value of this treatment in those with asthma is still debated. We evaluated the efficacy of SLIT in the treatment of allergic asthma in children by a metaanalysis of randomized, double-blind, and placebo-controlled (DBPC) clinical trials. Methods: Electronic databases were searched up to May 31, 2006, for randomized DBPC trials assessing SLIT in pediatric cases of asthma. Effects on primary outcomes (ie, symptom scores and concomitant use of rescue medication) were calculated with standardized mean differences (SMDs) using the random-effects model. We performed the metaanalysis using a statistical software package (RevMan, 4.2.8; The Cochrane Collaboration; Oxford, UK), and we followed the recommendations of the Cochrane Collaboration and the Quality of Reporting of Metaanalyses guidelines. Results: Seventy-three articles were identified and reviewed. Nine studies, all published after 1990, fulfilled the selection criteria. A total of 441 patients had a final assessment and were included in the analysis. Two hundred thirty-two patients received SLIT, and 209 patients received placebo. The results of the present analysis demonstrated a relevant heterogeneity due to widely differing scoring systems. Overall, there was a significant reduction in both symptoms (SMD 1.14; 95% confidence interval [CI], -2.10 to -0.18; p = 0.02) and medication use (SMD, 1.63; 95% CI, -2.83 to -0.44; p = 0.007) following SLIT. Conclusion: SLIT with standardized extracts reduces both symptom scores and rescue medication use in children with allergic asthma compared with placebo.. asthma| children| efficacy| metaanalysis| randomized controlled trials| sublingual immunotherapy|randomized controlled-trials| house-dust mite| double-blind| clinical-trials| grass-pollen| swallow immunotherapy| statistical power| respiratory allergy| double-dummy| children.	MAR-2008	asthma| children| efficacy| metaanalysis| randomized controlled trials| sublingual immunotherapy|randomized controlled-trials| house-dust mite| double-blind| clinical-trials| grass-pollen| swallow immunotherapy| statistical power| respiratory allergy| double-dummy| children	Penagos, M; Passalacqua, G; Compalati, E; Baena-Cagnani, CE; Orozco, S; Pedroza, A; Canonica, GW	Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age		CHEST	asthma; children; efficacy; metaanalysis; randomized controlled trials; sublingual immunotherapy	RANDOMIZED CONTROLLED-TRIALS; HOUSE-DUST MITE; DOUBLE-BLIND; CLINICAL-TRIALS; GRASS-POLLEN; SWALLOW IMMUNOTHERAPY; STATISTICAL POWER; RESPIRATORY ALLERGY; DOUBLE-DUMMY; CHILDREN	Background: Recent studies have documented the efficacy and safety of sublingual immunotherapy (SLIT) in patients with rhinitis, but the value of this treatment in those with asthma is still debated. We evaluated the efficacy of SLIT in the treatment of allergic asthma in children by a metaanalysis of randomized, double-blind, and placebo-controlled (DBPC) clinical trials. Methods: Electronic databases were searched up to May 31, 2006, for randomized DBPC trials assessing SLIT in pediatric cases of asthma. Effects on primary outcomes (ie, symptom scores and concomitant use of rescue medication) were calculated with standardized mean differences (SMDs) using the random-effects model. We performed the metaanalysis using a statistical software package (RevMan, 4.2.8; The Cochrane Collaboration; Oxford, UK), and we followed the recommendations of the Cochrane Collaboration and the Quality of Reporting of Metaanalyses guidelines. Results: Seventy-three articles were identified and reviewed. Nine studies, all published after 1990, fulfilled the selection criteria. A total of 441 patients had a final assessment and were included in the analysis. Two hundred thirty-two patients received SLIT, and 209 patients received placebo. The results of the present analysis demonstrated a relevant heterogeneity due to widely differing scoring systems. Overall, there was a significant reduction in both symptoms (SMD 1.14; 95% confidence interval [CI], -2.10 to -0.18; p = 0.02) and medication use (SMD, 1.63; 95% CI, -2.83 to -0.44; p = 0.007) following SLIT. Conclusion: SLIT with standardized extracts reduces both symptom scores and rescue medication use in children with allergic asthma compared with placebo.	76	164	2008	11	10.1378/chest.06-1425	General & Internal Medicine; Respiratory System
The link between allergic rhinitis and allergic asthma: A prospective population-based study. The Copenhagen Allergy Study. Background: It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma. Methods: Participants in a population-based study of 15-69-year-olds in 1990 were invited to a follow-up in 1998. A total of 734 subjects were examined on two occasions eight years apart. Allergic rhinitis to pollen was defined as a history of nasal symptoms on exposure to pollens and IgE specific to pollen. Allergic asthma to pollen was defined as a history of lower airway symptoms on exposure to pollens and IgE specific to pollen. Similarly, diagnoses of allergic rhinitis and allergic asthma to animals or mite were defined. Results: At follow-up, all subjects with allergic asthma to pollen (n = 52) had in addition allergic rhinitis to pollen. In the longitudinal analysis, there were a total of 28 new (incident) cases of allergic asthma to pollen. They all had allergic rhinitis to pollen at baseline, or had developed allergic rhinitis to pollen at follow-up. Accordingly, allergic rhinitis to animals and mite were ubiquitous in subjects with allergic asthma to animals and mite, respectively. Conclusions: The results support the hypothesis that allergic rhinitis and allergic asthma are manifestations of the same disease entity.. allergic asthma| allergic rhinitis| epidemiology| ige antibody| respiratory hypersensitivity|8 years apart| danish adults| skin-test| immunotherapy| prevalence.	NOV-2002	allergic asthma| allergic rhinitis| epidemiology| ige antibody| respiratory hypersensitivity|8 years apart| danish adults| skin-test| immunotherapy| prevalence	Linneberg, A; Nielsen, NH; Frolund, L; Madsen, F; Dirksen, A; Jorgensen, T	The link between allergic rhinitis and allergic asthma: A prospective population-based study. The Copenhagen Allergy Study		ALLERGY	allergic asthma; allergic rhinitis; epidemiology; IgE antibody; respiratory hypersensitivity	8 YEARS APART; DANISH ADULTS; SKIN-TEST; IMMUNOTHERAPY; PREVALENCE	Background: It has been hypothesized that allergic rhinitis and allergic asthma are manifestations of the same disease entity. We aimed to investigate the relationship between allergic rhinitis and allergic asthma. Methods: Participants in a population-based study of 15-69-year-olds in 1990 were invited to a follow-up in 1998. A total of 734 subjects were examined on two occasions eight years apart. Allergic rhinitis to pollen was defined as a history of nasal symptoms on exposure to pollens and IgE specific to pollen. Allergic asthma to pollen was defined as a history of lower airway symptoms on exposure to pollens and IgE specific to pollen. Similarly, diagnoses of allergic rhinitis and allergic asthma to animals or mite were defined. Results: At follow-up, all subjects with allergic asthma to pollen (n = 52) had in addition allergic rhinitis to pollen. In the longitudinal analysis, there were a total of 28 new (incident) cases of allergic asthma to pollen. They all had allergic rhinitis to pollen at baseline, or had developed allergic rhinitis to pollen at follow-up. Accordingly, allergic rhinitis to animals and mite were ubiquitous in subjects with allergic asthma to animals and mite, respectively. Conclusions: The results support the hypothesis that allergic rhinitis and allergic asthma are manifestations of the same disease entity.	27	164	2002	5	10.1034/j.1398-9995.2002.23664.x	Allergy; Immunology
Glucocorticoid receptor variants: clinical implications. Following exposure to stress, cortisol is secreted from the adrenal cortex under the control of the hypothalamic-pituitary-adrenal axis (HPA-axis). Central in the regulation of the HPA-axis is a two tied corticosteroid-receptor system, comprised of high and low affinity receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), respectively. In addition, these corticosteroid receptors mediate the effects of cortisol during stress on both central and peripheral targets. Cortisol modulates gene-expression of corticosteroid-responsive genes, with the effect lasting from hours to days. Mutations in the GR-gene are being associated with corticosteroid resistance and haematological malignancies, although these mutations are relatively rare and probably not a common cause of these diseases. However, several GR-gene variants and single nucleotide polymorphisms (SNP) in the GR-gene have been identified which are relatively common in the human population. The GRbeta-variant, for example, has been proposed to influence corticosteroid-sensitivity and most evidence has been derived from the immune system and in particular asthma. With respect to polymorphisms, a BclI restriction fragment polymorphism and a Asp363Ser have been described, which not only influence the regulation of the HPA-axis, but are also associated with changes in metabolism and cardiovascular control. These associations of a GR-gene polymorphism with metabolism and cardivascular control, and also with the regulation of the HPA-axis, indicates an important underlying role of cortisol in the etiology of these complex disorders. Therefore, we propose that a common underlying defect in these complex disorders is a disregulation of the HPA-axis, especially during stress. The clinical implication is that the regulation of the HPA-axis should be envisioned as a primary target of new drugs for the treatment of stress-related disorders. (C) 2002 Elsevier Science Ltd. All rights reserved.. glucocorticoid receptor variants| clinical implications| hypothalamic-pituitary-adrenal axis|primary cortisol resistance| fragment-length-polymorphism| hormone-binding domain| human multiple-myeloma| beta-isoform| dna-binding| messenger-rna| transcriptional activation| response element| cushings-disease.	JUN-2002	glucocorticoid receptor variants| clinical implications| hypothalamic-pituitary-adrenal axis|primary cortisol resistance| fragment-length-polymorphism| hormone-binding domain| human multiple-myeloma| beta-isoform| dna-binding| messenger-rna| transcriptional activation| response element| cushings-disease	DeRijk, RH; Schaaf, M; de Kloet, ER	Glucocorticoid receptor variants: clinical implications		JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY	glucocorticoid receptor variants; clinical implications; hypothalamic-pituitary-adrenal axis	PRIMARY CORTISOL RESISTANCE; FRAGMENT-LENGTH-POLYMORPHISM; HORMONE-BINDING DOMAIN; HUMAN MULTIPLE-MYELOMA; BETA-ISOFORM; DNA-BINDING; MESSENGER-RNA; TRANSCRIPTIONAL ACTIVATION; RESPONSE ELEMENT; CUSHINGS-DISEASE	Following exposure to stress, cortisol is secreted from the adrenal cortex under the control of the hypothalamic-pituitary-adrenal axis (HPA-axis). Central in the regulation of the HPA-axis is a two tied corticosteroid-receptor system, comprised of high and low affinity receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), respectively. In addition, these corticosteroid receptors mediate the effects of cortisol during stress on both central and peripheral targets. Cortisol modulates gene-expression of corticosteroid-responsive genes, with the effect lasting from hours to days. Mutations in the GR-gene are being associated with corticosteroid resistance and haematological malignancies, although these mutations are relatively rare and probably not a common cause of these diseases. However, several GR-gene variants and single nucleotide polymorphisms (SNP) in the GR-gene have been identified which are relatively common in the human population. The GRbeta-variant, for example, has been proposed to influence corticosteroid-sensitivity and most evidence has been derived from the immune system and in particular asthma. With respect to polymorphisms, a BclI restriction fragment polymorphism and a Asp363Ser have been described, which not only influence the regulation of the HPA-axis, but are also associated with changes in metabolism and cardiovascular control. These associations of a GR-gene polymorphism with metabolism and cardivascular control, and also with the regulation of the HPA-axis, indicates an important underlying role of cortisol in the etiology of these complex disorders. Therefore, we propose that a common underlying defect in these complex disorders is a disregulation of the HPA-axis, especially during stress. The clinical implication is that the regulation of the HPA-axis should be envisioned as a primary target of new drugs for the treatment of stress-related disorders. (C) 2002 Elsevier Science Ltd. All rights reserved.	151	164	2002	20	10.1016/S0960-0760(02)00062-6	Biochemistry & Molecular Biology; Endocrinology & Metabolism
Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care. Background-Chronic obstructive pulmonary disease (COPD) is common although often poorly characterised, particularly in primary care. However, application of guidelines to the management of such patients needs a clear understanding of the phenotype. In particular, the British guidelines for the management of COPD recommend that the diagnosis is based on appropriate symptoms and evidence of airflow obstruction as determined by a forced expiratory volume in one second (FEV1) of <80% of the predicted value and an FEV1/VC ratio of <70%. Methods-A study was undertaken of 110 patients aged 40-80 years who had presented to their general practitioner with an acute exacerbation of COPD. The episode was treated at home and, when patients had recovered to the stable state (two months later), they were characterised by full lung function tests and a high resolution computed tomographic (HRCT) scan of the chest. Results-There was a wide range of impairment of FEV1 which was in the normal range (greater than or equal to 80%) in 30%, mildly impaired (60-79%) in 18%, moderately impaired (40-59%) in 33%, and severely impaired (<40%) in 19% of patients. A reduced FEV1/VC ratio was present in all patients with an FEV1 of <80% predicted but also in 41% of those with an FEV1 of greater than or equal to 80% predicted. Only 5% of patients had a substantial bronchodilator response suggesting a diagnosis of asthma. Emphysema was present in 51% of patients and confined to the upper lobes in most (73% of these patients). HRCT evidence of bronchiectasis was noted in 29% of patients and was predominantly tubular; most (81%) were current or ex-smokers. A solitary pulmonary nodule was seen on 9% of scans and unsuspected lung malignancy was diagnosed in two patients. Conclusions-This study confirms that COPD in primary care is a heterogeneous condition. Some patients do not fulfil the proposed diagnostic criteria with FEV1 of greater than or equal to 80% predicted but they may nevertheless have airflow obstruction. Bronchiectasis is common in this group of patients, as is unsuspected malignancy. These findings should be considered when developing recommendations for the investigation and management of COPD in the community.. chronic obstructive pulmonary disease| bronchiectasis| lung function tests| radiology|chronic sputum production| computed-tomography| function tests| lung| chest| exacerbations| management| emphysema| smokers| copd.	AUG-2000	chronic obstructive pulmonary disease| bronchiectasis| lung function tests| radiology|chronic sputum production| computed-tomography| function tests| lung| chest| exacerbations| management| emphysema| smokers| copd	O'Brien, C; Guest, PJ; Hill, SL; Stockley, RA	Physiological and radiological characterisation of patients diagnosed with chronic obstructive pulmonary disease in primary care		THORAX	chronic obstructive pulmonary disease; bronchiectasis; lung function tests; radiology	CHRONIC SPUTUM PRODUCTION; COMPUTED-TOMOGRAPHY; FUNCTION TESTS; LUNG; CHEST; EXACERBATIONS; MANAGEMENT; EMPHYSEMA; SMOKERS; COPD	Background-Chronic obstructive pulmonary disease (COPD) is common although often poorly characterised, particularly in primary care. However, application of guidelines to the management of such patients needs a clear understanding of the phenotype. In particular, the British guidelines for the management of COPD recommend that the diagnosis is based on appropriate symptoms and evidence of airflow obstruction as determined by a forced expiratory volume in one second (FEV1) of <80% of the predicted value and an FEV1/VC ratio of <70%. Methods-A study was undertaken of 110 patients aged 40-80 years who had presented to their general practitioner with an acute exacerbation of COPD. The episode was treated at home and, when patients had recovered to the stable state (two months later), they were characterised by full lung function tests and a high resolution computed tomographic (HRCT) scan of the chest. Results-There was a wide range of impairment of FEV1 which was in the normal range (greater than or equal to 80%) in 30%, mildly impaired (60-79%) in 18%, moderately impaired (40-59%) in 33%, and severely impaired (<40%) in 19% of patients. A reduced FEV1/VC ratio was present in all patients with an FEV1 of <80% predicted but also in 41% of those with an FEV1 of greater than or equal to 80% predicted. Only 5% of patients had a substantial bronchodilator response suggesting a diagnosis of asthma. Emphysema was present in 51% of patients and confined to the upper lobes in most (73% of these patients). HRCT evidence of bronchiectasis was noted in 29% of patients and was predominantly tubular; most (81%) were current or ex-smokers. A solitary pulmonary nodule was seen on 9% of scans and unsuspected lung malignancy was diagnosed in two patients. Conclusions-This study confirms that COPD in primary care is a heterogeneous condition. Some patients do not fulfil the proposed diagnostic criteria with FEV1 of greater than or equal to 80% predicted but they may nevertheless have airflow obstruction. Bronchiectasis is common in this group of patients, as is unsuspected malignancy. These findings should be considered when developing recommendations for the investigation and management of COPD in the community.	29	164	2000	8	10.1136/thorax.55.8.635	Respiratory System
Modulation of the immune system by UV radiation: more than just the effects of vitamin D?. Humans obtain most of their vitamin D through the exposure of skin to sunlight. The immunoregulatory properties of vitamin D have been demonstrated in studies showing that vitamin D deficiency is associated with poor immune function and increased disease susceptibility. The benefits of moderate ultraviolet (UV) radiation exposure and the positive latitude gradients observed for some immune-mediated diseases may therefore reflect the activities of UV-induced vitamin D. Alternatively, other mediators that are induced by UV radiation may be more important for UV-mediated immunomodulation. Here, we compare and contrast the effects of UV radiation and vitamin D on immune function in immunopathological diseases, such as psoriasis, multiple sclerosis and asthma, and during infection.. regulatory-t-cells| ultraviolet-radiation| multiple-sclerosis| urocanic acid| induced immunosuppression| human skin| antimicrobial peptides| induced suppression| mast-cells| infectious-diseases.	SEP-2011	regulatory-t-cells| ultraviolet-radiation| multiple-sclerosis| urocanic acid| induced immunosuppression| human skin| antimicrobial peptides| induced suppression| mast-cells| infectious-diseases	Hart, PH; Gorman, S; Finlay-JonesO, JJ	Modulation of the immune system by UV radiation: more than just the effects of vitamin D?		NATURE REVIEWS IMMUNOLOGY		REGULATORY-T-CELLS; ULTRAVIOLET-RADIATION; MULTIPLE-SCLEROSIS; UROCANIC ACID; INDUCED IMMUNOSUPPRESSION; HUMAN SKIN; ANTIMICROBIAL PEPTIDES; INDUCED SUPPRESSION; MAST-CELLS; INFECTIOUS-DISEASES	Humans obtain most of their vitamin D through the exposure of skin to sunlight. The immunoregulatory properties of vitamin D have been demonstrated in studies showing that vitamin D deficiency is associated with poor immune function and increased disease susceptibility. The benefits of moderate ultraviolet (UV) radiation exposure and the positive latitude gradients observed for some immune-mediated diseases may therefore reflect the activities of UV-induced vitamin D. Alternatively, other mediators that are induced by UV radiation may be more important for UV-mediated immunomodulation. Here, we compare and contrast the effects of UV radiation and vitamin D on immune function in immunopathological diseases, such as psoriasis, multiple sclerosis and asthma, and during infection.	111	163	2011	13	10.1038/nri3045	Immunology
Can early introduction of egg prevent egg allergy in infants? A population-based study. Background: Infant feeding guidelines have long recommended delaying introduction of solids and allergenic foods to prevent allergy in high-risk infants, despite a paucity of evidence. Objective: We aimed to determine whether confirmed egg allergy in 12-month-old infants is associated with (1) duration of breast-feeding and (2) ages of introducing egg and solids. Methods: In a population-based cross-sectional study (HealthNuts) parents reported on infant feeding and potential confounding factors before skin prick testing for egg white. Egg-sensitized infants were then offered an egg oral food challenge. Multiple logistic regression was used to investigate associations between diet and egg allergy adjusted for possible confounding factors. Results: A total of 2589 infants (73% response) participated. Compared with introduction at 4 to 6 months, introducing egg into the diet later was associated with higher risks of egg allergy (adjusted odds ratios [ORs], 1.6 [95% CI, 1.0-2.6] and 3.4 [95% CI, 1.8-6.5] for introduction at 10-12 and after 12 months, respectively). These findings persisted even in children without risk factors (OR, 3.3 [95% CI, 1.1-9.9]; 10-12 months). At age 4 to 6 months, first exposure as cooked egg reduced the risk of egg allergy compared with first exposure as egg in baked goods (OR, 0.2 [95% CI, 0.06-0.71]). Duration of breast-feeding and age at introduction of solids were not associated with egg allergy. Conclusions: Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. Changes in infant feeding guidelines could have a significant effect on childhood egg allergy and possibly food allergy more generally. (J Allergy Clin Immunol 2010;126:807-13.). egg allergy| food allergy| solids| breast-feeding| infant diet| weaning|atopic disease| oral tolerance| peanut allergy| food allergy| birth cohort| children| risk| life| sensitization| consumption.	OCT-2010	egg allergy| food allergy| solids| breast-feeding| infant diet| weaning|atopic disease| oral tolerance| peanut allergy| food allergy| birth cohort| children| risk| life| sensitization| consumption	Koplin, JJ; Osborne, NJ; Wake, M; Martin, PE; Gurrin, LC; Robinson, MN; Tey, D; Slaa, M; Thiele, L; Miles, L; Anderson, D; Tan, T; Dang, TD; Hill, DJ; Lowe, AJ; Matheson, MC; Ponsonby, AL; Tang, MLK; Dharmage, SC; Allen, KJ	Can early introduction of egg prevent egg allergy in infants? A population-based study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Egg allergy; food allergy; solids; breast-feeding; infant diet; weaning	ATOPIC DISEASE; ORAL TOLERANCE; PEANUT ALLERGY; FOOD ALLERGY; BIRTH COHORT; CHILDREN; RISK; LIFE; SENSITIZATION; CONSUMPTION	Background: Infant feeding guidelines have long recommended delaying introduction of solids and allergenic foods to prevent allergy in high-risk infants, despite a paucity of evidence. Objective: We aimed to determine whether confirmed egg allergy in 12-month-old infants is associated with (1) duration of breast-feeding and (2) ages of introducing egg and solids. Methods: In a population-based cross-sectional study (HealthNuts) parents reported on infant feeding and potential confounding factors before skin prick testing for egg white. Egg-sensitized infants were then offered an egg oral food challenge. Multiple logistic regression was used to investigate associations between diet and egg allergy adjusted for possible confounding factors. Results: A total of 2589 infants (73% response) participated. Compared with introduction at 4 to 6 months, introducing egg into the diet later was associated with higher risks of egg allergy (adjusted odds ratios [ORs], 1.6 [95% CI, 1.0-2.6] and 3.4 [95% CI, 1.8-6.5] for introduction at 10-12 and after 12 months, respectively). These findings persisted even in children without risk factors (OR, 3.3 [95% CI, 1.1-9.9]; 10-12 months). At age 4 to 6 months, first exposure as cooked egg reduced the risk of egg allergy compared with first exposure as egg in baked goods (OR, 0.2 [95% CI, 0.06-0.71]). Duration of breast-feeding and age at introduction of solids were not associated with egg allergy. Conclusions: Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. Changes in infant feeding guidelines could have a significant effect on childhood egg allergy and possibly food allergy more generally. (J Allergy Clin Immunol 2010;126:807-13.)	29	163	2010	7	10.1016/j.jaci.2010.07.028	Allergy; Immunology
The health effects of nonindustrial indoor air pollution. Background: There is growing public awareness regarding the risk associated with poor indoor air quality in the home and workplace. Because Americans spend approximately 22 hours every day indoors, susceptible individuals are at much greater risk of adverse health effects from chronic low levels of exposure to indoor air pollutants over time. Along with particulate matter, gases such as ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide; microbial and chemical volatile organic compounds; passive smoke; and outdoor ambient air are the most common types of air pollutants encountered indoors. Objective: To provide the allergists with necessary information that will assist them in making useful recommendations to patients seeking advice regarding indoor environmental triggers beyond traditional perennial allergens. Methods: Review of the literature pertaining to indoor exposure and health effects of gaseous and particular matter. Results: Indoor pollutants act as respiratory irritants, toxicants, and adjuvants or carriers of allergens. Conclusion: The allergist should be prepared to evaluate patient exposure to allergic and nonallergic triggers and understand how outdoor air pollution is affecting indoor environments. This requires being familiar with methodologies for monitoring and interpreting indoor air quality and interpreting results in the context of the patients exposure history and advising patients about rational environmental control interventions.. indoor air pollutants| ozone| particulate matter| nitrogen dioxide| carbon monoxide| sulfur dioxide| health effects| volatile organic compounds| tobacco smoke| passive smoke exposure| cotinine| fungal allergens|environmental tobacco-smoke| volatile organic-compounds| nitrogen-dioxide exposure| respiratory symptoms| stachybotrys-chartarum| particulate matter| ozone exposure| sensory irritation| inhaled allergen| oxidative stress.	MAR-2008	indoor air pollutants| ozone| particulate matter| nitrogen dioxide| carbon monoxide| sulfur dioxide| health effects| volatile organic compounds| tobacco smoke| passive smoke exposure| cotinine| fungal allergens|environmental tobacco-smoke| volatile organic-compounds| nitrogen-dioxide exposure| respiratory symptoms| stachybotrys-chartarum| particulate matter| ozone exposure| sensory irritation| inhaled allergen| oxidative stress	Bernstein, JA; Alexis, N; Bacchus, H; Bernstein, IL; Fritz, P; Horner, E; Li, N; Mason, S; Nel, A; Oullette, J; Reijula, K; Reponen, T; Seltzer, J; Smith, A; Tarlo, SM	The health effects of nonindustrial indoor air pollution		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	indoor air pollutants; ozone; particulate matter; nitrogen dioxide; carbon monoxide; sulfur dioxide; health effects; volatile organic compounds; tobacco smoke; passive smoke exposure; cotinine; fungal allergens	ENVIRONMENTAL TOBACCO-SMOKE; VOLATILE ORGANIC-COMPOUNDS; NITROGEN-DIOXIDE EXPOSURE; RESPIRATORY SYMPTOMS; STACHYBOTRYS-CHARTARUM; PARTICULATE MATTER; OZONE EXPOSURE; SENSORY IRRITATION; INHALED ALLERGEN; OXIDATIVE STRESS	Background: There is growing public awareness regarding the risk associated with poor indoor air quality in the home and workplace. Because Americans spend approximately 22 hours every day indoors, susceptible individuals are at much greater risk of adverse health effects from chronic low levels of exposure to indoor air pollutants over time. Along with particulate matter, gases such as ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide; microbial and chemical volatile organic compounds; passive smoke; and outdoor ambient air are the most common types of air pollutants encountered indoors. Objective: To provide the allergists with necessary information that will assist them in making useful recommendations to patients seeking advice regarding indoor environmental triggers beyond traditional perennial allergens. Methods: Review of the literature pertaining to indoor exposure and health effects of gaseous and particular matter. Results: Indoor pollutants act as respiratory irritants, toxicants, and adjuvants or carriers of allergens. Conclusion: The allergist should be prepared to evaluate patient exposure to allergic and nonallergic triggers and understand how outdoor air pollution is affecting indoor environments. This requires being familiar with methodologies for monitoring and interpreting indoor air quality and interpreting results in the context of the patients exposure history and advising patients about rational environmental control interventions.	76	163	2008	7	10.1016/j.jaci.2007.10.045	Allergy; Immunology
Multicenter study of emergency department visits for food allergies. Background: Relatively little is known about the characteristics of patients who visit the emergency department (ED) for an acute allergic reaction. Although anaphylaxis guidelines suggest treatment with epinephrine, teaching about self-injectable epinephrine, and referral to an allergist, current ED management remains uncertain. Objective: The objective of this study was to describe the management of food-related acute allergic reactions. Methods: The Multicenter Airway Research Collaboration performed a chart review study in 21 North American EDs. Investigators reviewed a random sample of 678 charts of patients who presented with food allergy (International Classification of Diseases-ninth revision codes 693.1, 995.0, 995.3, and 995.60-995.69). Results: Patients had an average age of 29 years; the cohort was 57% female and 40% white. A variety of foods provoked the allergic reaction, including nuts (21%), crustaceans (19%), fruit (12%), and fish (10%). Although exposure to these foods can be life threatening, only 18% of patients came to the ED by ambulance. In the ED, 72% of patients received antihistamines, 48% received systemic corticosteroids, and 16% received epinephrine; 33% received respiratory treatments such as inhaled albuterol. Among patients with severe reactions (55% of total), 24% received epinephrine. Overall, 97% of patients were discharged to home. At ED discharge, 16% of patients were prescribed self-injectable epinephrine, and 12% were referred to an allergist. Conclusions: Although guidelines suggest specific approaches for the management of acute allergic reactions, ED concordance for food allergy appears low. These findings support a new collaboration between professional organizations in allergy and emergency medicine and the development of educational programs and materials for ED patients and staff.. food allergy| emergency department| epinephrine|anaphylactic reactions| epidemiology| room.	FEB-2004	food allergy| emergency department| epinephrine|anaphylactic reactions| epidemiology| room	Clark, S; Bock, SA; Gaeta, TJ; Brenner, BE; Cydulka, RK; Camargo, CA	Multicenter study of emergency department visits for food allergies		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	food allergy; emergency department; epinephrine	ANAPHYLACTIC REACTIONS; EPIDEMIOLOGY; ROOM	Background: Relatively little is known about the characteristics of patients who visit the emergency department (ED) for an acute allergic reaction. Although anaphylaxis guidelines suggest treatment with epinephrine, teaching about self-injectable epinephrine, and referral to an allergist, current ED management remains uncertain. Objective: The objective of this study was to describe the management of food-related acute allergic reactions. Methods: The Multicenter Airway Research Collaboration performed a chart review study in 21 North American EDs. Investigators reviewed a random sample of 678 charts of patients who presented with food allergy (International Classification of Diseases-ninth revision codes 693.1, 995.0, 995.3, and 995.60-995.69). Results: Patients had an average age of 29 years; the cohort was 57% female and 40% white. A variety of foods provoked the allergic reaction, including nuts (21%), crustaceans (19%), fruit (12%), and fish (10%). Although exposure to these foods can be life threatening, only 18% of patients came to the ED by ambulance. In the ED, 72% of patients received antihistamines, 48% received systemic corticosteroids, and 16% received epinephrine; 33% received respiratory treatments such as inhaled albuterol. Among patients with severe reactions (55% of total), 24% received epinephrine. Overall, 97% of patients were discharged to home. At ED discharge, 16% of patients were prescribed self-injectable epinephrine, and 12% were referred to an allergist. Conclusions: Although guidelines suggest specific approaches for the management of acute allergic reactions, ED concordance for food allergy appears low. These findings support a new collaboration between professional organizations in allergy and emergency medicine and the development of educational programs and materials for ED patients and staff.	18	163	2004	6	10.1016/j.jaci.2003.10.053	Allergy; Immunology
Inhaled corticosteroids: Impact on asthma morbidity and mortality. Inhaled corticosteroids are now recommended as first-line therapy for asthma, Although these drugs clearly improve the symptoms of the disease and the associated physiologic abnormalities, epidemiologic studies provide important information on their effectiveness in preventing asthma morbidity and mortality. We review the evidence regarding the role of inhaled corticosteroids in the prevention of asthma fatality and hospitalization. In the process, we discuss the methodologic complexities of the nonexperimental studies and the implications of the methodologic issues on the evaluation of the impart of these drugs. Eight of the cohort and ecologic studies conducted to date strongly suggest that inhaled corticosteroids. when taken regularly, decrease the number of hospitalizations for asthma by up to 80%. For asthma death, the results of 11 investigations appear less consistent, especially those of several cohort and case-control studies whose principal objective was to examine not the benefit of inhaled corticosteroids but the adverse effects of other drug classes, Much of the inconsistency in the results, however, can be explained by weaknesses in study design and analysis-in particular, the failure to consider exposure in terms of regular use of inhaled corticosteroids. When the most recent study involving the use of the Saskatchewan databases is considered, it is evident that regular treatment with conventional or low-dose inhaled corticosteroids results in a significant reduction in fatalities due to asthma, In all, the evidence to date strongly indicates that regular use of inhaled corticosteroids, even at low doses, would prevent the major portion of asthma hospitalizations and deaths.. asthma| case-control studies| cohort studies| ecologic studies| epidemiologic studies| hospitalization| inhaled glucocorticoids| mortality| registries|new-zealand| prescribed fenoterol| hospital admission| childhood asthma| beta-agonists| united-states| young-adults| risk-factors| mild asthma| death.	JUN-2001	asthma| case-control studies| cohort studies| ecologic studies| epidemiologic studies| hospitalization| inhaled glucocorticoids| mortality| registries|new-zealand| prescribed fenoterol| hospital admission| childhood asthma| beta-agonists| united-states| young-adults| risk-factors| mild asthma| death	Suissa, S; Ernst, P	Inhaled corticosteroids: Impact on asthma morbidity and mortality		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; case-control studies; cohort studies; ecologic studies; epidemiologic studies; hospitalization; inhaled glucocorticoids; mortality; registries	NEW-ZEALAND; PRESCRIBED FENOTEROL; HOSPITAL ADMISSION; CHILDHOOD ASTHMA; BETA-AGONISTS; UNITED-STATES; YOUNG-ADULTS; RISK-FACTORS; MILD ASTHMA; DEATH	Inhaled corticosteroids are now recommended as first-line therapy for asthma, Although these drugs clearly improve the symptoms of the disease and the associated physiologic abnormalities, epidemiologic studies provide important information on their effectiveness in preventing asthma morbidity and mortality. We review the evidence regarding the role of inhaled corticosteroids in the prevention of asthma fatality and hospitalization. In the process, we discuss the methodologic complexities of the nonexperimental studies and the implications of the methodologic issues on the evaluation of the impart of these drugs. Eight of the cohort and ecologic studies conducted to date strongly suggest that inhaled corticosteroids. when taken regularly, decrease the number of hospitalizations for asthma by up to 80%. For asthma death, the results of 11 investigations appear less consistent, especially those of several cohort and case-control studies whose principal objective was to examine not the benefit of inhaled corticosteroids but the adverse effects of other drug classes, Much of the inconsistency in the results, however, can be explained by weaknesses in study design and analysis-in particular, the failure to consider exposure in terms of regular use of inhaled corticosteroids. When the most recent study involving the use of the Saskatchewan databases is considered, it is evident that regular treatment with conventional or low-dose inhaled corticosteroids results in a significant reduction in fatalities due to asthma, In all, the evidence to date strongly indicates that regular use of inhaled corticosteroids, even at low doses, would prevent the major portion of asthma hospitalizations and deaths.	71	163	2001	8	10.1067/mai.2001.115653	Allergy; Immunology
A meta-analysis of the effect of high weight on asthma. Background: Prevalence rates for both overweight and asthma have been increasing among children in developed countries over the past two decades. Some recent studies have postulated a causal relation between these but have lacked power to form a definitive conclusion. Aim: To estimate the effect of high body weight in childhood on the future risk of asthma. Methods: Medline search ( 1966 to October 2004), supplemented by manual search of reference lists and grey literature. Cohort studies that examined high body weight at birth or during childhood and future outcome of asthma were included. Data from each study were extracted on exposure status, clinical outcome, and study characteristics. Results: A total of 402 studies were initially identified, of which 12 met the inclusion criteria. The combined results from four studies that examined the effect of high body weight during middle childhood on the outcome of subsequent asthma showed a 50% increase in relative risk (RR 1.5, 95% CI 1.2 to 1.8). The combined results from nine studies that examined the effect of high birth weight on subsequent asthma had a pooled RR of 1.2 ( 95% CI 1.1 to 1.3). There was consistency among the results in sensitivity analyses examining studies containing only estimates of odds ratios, studies containing only the outcome of physician diagnosis of asthma, and studies including all definitions of high body weight. Conclusions: Children with high body weight, either at birth or later in childhood, are at increased risk for future asthma. Potential biological mechanisms include diet, gastro-oesophageal reflux, mechanical effects of obesity, atopy, and hormonal influences. Further research might elucidate the causal pathway, which could improve our understanding of the pathophysiology of asthma and perhaps lead to knowledge of potential preventive interventions.. body-mass index| united-states| birth-weight| fetal-growth| risk-factors| nutrition examination| childhood asthma| national-health| lung-function| young-adults.	APR-2006	body-mass index| united-states| birth-weight| fetal-growth| risk-factors| nutrition examination| childhood asthma| national-health| lung-function| young-adults	Flaherman, V; Rutherford, GW	A meta-analysis of the effect of high weight on asthma		ARCHIVES OF DISEASE IN CHILDHOOD		BODY-MASS INDEX; UNITED-STATES; BIRTH-WEIGHT; FETAL-GROWTH; RISK-FACTORS; NUTRITION EXAMINATION; CHILDHOOD ASTHMA; NATIONAL-HEALTH; LUNG-FUNCTION; YOUNG-ADULTS	Background: Prevalence rates for both overweight and asthma have been increasing among children in developed countries over the past two decades. Some recent studies have postulated a causal relation between these but have lacked power to form a definitive conclusion. Aim: To estimate the effect of high body weight in childhood on the future risk of asthma. Methods: Medline search ( 1966 to October 2004), supplemented by manual search of reference lists and grey literature. Cohort studies that examined high body weight at birth or during childhood and future outcome of asthma were included. Data from each study were extracted on exposure status, clinical outcome, and study characteristics. Results: A total of 402 studies were initially identified, of which 12 met the inclusion criteria. The combined results from four studies that examined the effect of high body weight during middle childhood on the outcome of subsequent asthma showed a 50% increase in relative risk (RR 1.5, 95% CI 1.2 to 1.8). The combined results from nine studies that examined the effect of high birth weight on subsequent asthma had a pooled RR of 1.2 ( 95% CI 1.1 to 1.3). There was consistency among the results in sensitivity analyses examining studies containing only estimates of odds ratios, studies containing only the outcome of physician diagnosis of asthma, and studies including all definitions of high body weight. Conclusions: Children with high body weight, either at birth or later in childhood, are at increased risk for future asthma. Potential biological mechanisms include diet, gastro-oesophageal reflux, mechanical effects of obesity, atopy, and hormonal influences. Further research might elucidate the causal pathway, which could improve our understanding of the pathophysiology of asthma and perhaps lead to knowledge of potential preventive interventions.	48	162	2006	6	10.1136/adc.2005.080390	Pediatrics
Protein kinase C theta is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses. The serine/threonine-specific protein kinase C (PKC)-theta is predominantly expressed in T cells and localizes to the center of the immunological synapse upon T cell receptor (TCR) and CD28 signaling. T cells deficient in PKC-theta exhibit reduced interleukin (IL)-2 production and proliferative responses in vitro, however, its significance in vivo remains unclear. We found that pkc-theta(-/-) mice were protected from pulmonary allergic hypersensitivity responses such as air-way hyperresponsiveness, eosinophilia, and immunoglobulin E production to inhaled allergen. Furthermore, T helper (Th)2 cell immune responses against Nippostrongylus brasiliensis were severely impaired in pkc-theta(-/-) mice. In striking contrast, pkc-theta(-/-) mice on both the C57BL/6 background and the normally susceptible BALB/c background mounted protective Th1 immune responses and were resistant against infection with Leishmania major. Using in vitro TCR transgenic T cell-dendritic cell coculture systems and antigen concentration-dependent Th polarization, PKC-theta-deficient T cells were found to differentiate into Th1 cells after activation with high concentrations of specific peptide, but to have compromised Th2 development at low antigen concentration. The addition of IL-2 partially reconstituted Th2 development in pkc-theta(-/-) T cells, consistent with an important role for this cytokine in Th2 polarization. Taken together, our results reveal a central role for PKC-theta signaling during Th2 responses.. pkc-theta| asthma| leishmania| nippostrongylus| th2 cell|nf-kappa-b| allergic airway inflammation| pkc-theta| immunological synapse| interferon-gamma| cutaneous leishmaniasis| t(h)2 differentiation| activation| interleukin-4| expression.	JUL 19-2004	pkc-theta| asthma| leishmania| nippostrongylus| th2 cell|nf-kappa-b| allergic airway inflammation| pkc-theta| immunological synapse| interferon-gamma| cutaneous leishmaniasis| t(h)2 differentiation| activation| interleukin-4| expression	Marsland, BJ; Soos, TJ; Spath, G; Littman, DR; Kopf, M	Protein kinase C theta is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses		JOURNAL OF EXPERIMENTAL MEDICINE	PKC-theta; asthma; Leishmania; nippostrongylus; Th2 cell	NF-KAPPA-B; ALLERGIC AIRWAY INFLAMMATION; PKC-THETA; IMMUNOLOGICAL SYNAPSE; INTERFERON-GAMMA; CUTANEOUS LEISHMANIASIS; T(H)2 DIFFERENTIATION; ACTIVATION; INTERLEUKIN-4; EXPRESSION	The serine/threonine-specific protein kinase C (PKC)-theta is predominantly expressed in T cells and localizes to the center of the immunological synapse upon T cell receptor (TCR) and CD28 signaling. T cells deficient in PKC-theta exhibit reduced interleukin (IL)-2 production and proliferative responses in vitro, however, its significance in vivo remains unclear. We found that pkc-theta(-/-) mice were protected from pulmonary allergic hypersensitivity responses such as air-way hyperresponsiveness, eosinophilia, and immunoglobulin E production to inhaled allergen. Furthermore, T helper (Th)2 cell immune responses against Nippostrongylus brasiliensis were severely impaired in pkc-theta(-/-) mice. In striking contrast, pkc-theta(-/-) mice on both the C57BL/6 background and the normally susceptible BALB/c background mounted protective Th1 immune responses and were resistant against infection with Leishmania major. Using in vitro TCR transgenic T cell-dendritic cell coculture systems and antigen concentration-dependent Th polarization, PKC-theta-deficient T cells were found to differentiate into Th1 cells after activation with high concentrations of specific peptide, but to have compromised Th2 development at low antigen concentration. The addition of IL-2 partially reconstituted Th2 development in pkc-theta(-/-) T cells, consistent with an important role for this cytokine in Th2 polarization. Taken together, our results reveal a central role for PKC-theta signaling during Th2 responses.	40	162	2004	9	10.1084/jem.20032229	Immunology; Research & Experimental Medicine
Toll-like receptor 4 is required for optimal development of Th2 immune responses: Role of dendritic cells. LPS potently induces dendritic cell maturation and the production of proinflammatory cytokines, such as IL-12, by activation of Toll-like receptor 4 (TLR4). Since IL-12 is important for the generation and maintenance of Th1 responses and may also inhibit Th2 cell generation from naive CD4 T cell precursors, it has been inferred that TLR4 signaling would have similar effects via the induction of IL-12 secretion. Surprisingly, we found that TLR4-defective mice subjected to sensitization and pulmonary challenge with a protein allergen had reductions in airway inflammation with eosinophils, allergen-specific IgE levels, and Th2 cytokine production, compared with wild-type mice. These reduced responses were attributable, at least in part, to decreased dendritic cell function: Dendritic cells from TLR4-defective mice expressed lower levels of CD86, a costimulatory molecule important for The responses. They also induced less Th2 cytokine production by antigenically naive CD4 T cells in vitro and mediated diminished CD4 T cell Ag-specific pulmonary inflammation in vivo. These results indicate that TLR4 is required for optimal Th2 responses to Ags from nonpathogenic sources and suggest a role for TLR4 ligands, such as LPS derived from commensal bacteria or endogenously derived ligands, in maturation of the innate immune system before pathogen exposure.. leishmania-major infection| house-dust endotoxin| ifn-gamma production| t-cells| adaptive immunity| signaling pathway| allergic-asthma| cutting edge| mast-cells| b7-2 cd86.	MAY 1-2002	leishmania-major infection| house-dust endotoxin| ifn-gamma production| t-cells| adaptive immunity| signaling pathway| allergic-asthma| cutting edge| mast-cells| b7-2 cd86	Dabbagh, K; Dahl, ME; Stepick-Biek, P; Lewis, DB	Toll-like receptor 4 is required for optimal development of Th2 immune responses: Role of dendritic cells		JOURNAL OF IMMUNOLOGY		LEISHMANIA-MAJOR INFECTION; HOUSE-DUST ENDOTOXIN; IFN-GAMMA PRODUCTION; T-CELLS; ADAPTIVE IMMUNITY; SIGNALING PATHWAY; ALLERGIC-ASTHMA; CUTTING EDGE; MAST-CELLS; B7-2 CD86	LPS potently induces dendritic cell maturation and the production of proinflammatory cytokines, such as IL-12, by activation of Toll-like receptor 4 (TLR4). Since IL-12 is important for the generation and maintenance of Th1 responses and may also inhibit Th2 cell generation from naive CD4 T cell precursors, it has been inferred that TLR4 signaling would have similar effects via the induction of IL-12 secretion. Surprisingly, we found that TLR4-defective mice subjected to sensitization and pulmonary challenge with a protein allergen had reductions in airway inflammation with eosinophils, allergen-specific IgE levels, and Th2 cytokine production, compared with wild-type mice. These reduced responses were attributable, at least in part, to decreased dendritic cell function: Dendritic cells from TLR4-defective mice expressed lower levels of CD86, a costimulatory molecule important for The responses. They also induced less Th2 cytokine production by antigenically naive CD4 T cells in vitro and mediated diminished CD4 T cell Ag-specific pulmonary inflammation in vivo. These results indicate that TLR4 is required for optimal Th2 responses to Ags from nonpathogenic sources and suggest a role for TLR4 ligands, such as LPS derived from commensal bacteria or endogenously derived ligands, in maturation of the innate immune system before pathogen exposure.	63	162	2002	7		Immunology
SQ-standardized sublingual grass immunotherapy: Confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. Background: The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials. Objective: To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU,* ALK, Denmark) or placebo. Methods: A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters. Results: The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% (P <= .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by20% to45%(P <= .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% (P <= .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% (P <= .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified. Conclusion: The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis. (J Allergy Clin Immunol 2012; 129: 717-25.). allergy immunotherapy tablet| disease modification| grass pollen| immunotherapy| sublingual| sustained efficacy| placebo-controlled| phleum pratense| rhinoconjunctivitis| rhinoconjunctivitis quality of life|allergic rhinitis| follow-up| rhinoconjunctivitis| efficacy| tablet| children| asthma| safety| prevalence| mechanisms.	MAR-2012	allergy immunotherapy tablet| disease modification| grass pollen| immunotherapy| sublingual| sustained efficacy| placebo-controlled| phleum pratense| rhinoconjunctivitis| rhinoconjunctivitis quality of life|allergic rhinitis| follow-up| rhinoconjunctivitis| efficacy| tablet| children| asthma| safety| prevalence| mechanisms	Durham, SR; Emminger, W; Kapp, A; de Monchy, JGR; Rak, S; Scadding, GK; Wurtzen, PA; Andersen, JS; Tholstrup, B; Riis, B; Dahl, R	SQ-standardized sublingual grass immunotherapy: Confirmation of disease modification 2 years after 3 years of treatment in a randomized trial		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergy immunotherapy tablet; disease modification; grass pollen; immunotherapy; sublingual; sustained efficacy; placebo-controlled; Phleum pratense; rhinoconjunctivitis; rhinoconjunctivitis quality of life	ALLERGIC RHINITIS; FOLLOW-UP; RHINOCONJUNCTIVITIS; EFFICACY; TABLET; CHILDREN; ASTHMA; SAFETY; PREVALENCE; MECHANISMS	Background: The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials. Objective: To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU,* ALK, Denmark) or placebo. Methods: A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters. Results: The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% (P <= .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by20% to45%(P <= .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% (P <= .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% (P <= .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified. Conclusion: The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis. (J Allergy Clin Immunol 2012; 129: 717-25.)	36	161	2012	14	10.1016/j.jaci.2011.12.973	Allergy; Immunology
Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9(-/-) knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78-treated TLR2/3/4/7/9(-/-) homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78-exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.. allergic sensitization| airway inflammation| dendritic cells| exposure| children| risk| farm| lipopolysaccharide| recognition| expression.	DEC 21-2009	allergic sensitization| airway inflammation| dendritic cells| exposure| children| risk| farm| lipopolysaccharide| recognition| expression	Conrad, ML; Ferstl, R; Teich, R; Brand, S; Blumer, N; Yildirim, AO; Patrascan, CC; Hanuszkiewicz, A; Akira, S; Wagner, H; Holst, O; von Mutius, E; Pfefferle, PI; Kirschning, CJ; Garn, H; Renz, H	Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78		JOURNAL OF EXPERIMENTAL MEDICINE		ALLERGIC SENSITIZATION; AIRWAY INFLAMMATION; DENDRITIC CELLS; EXPOSURE; CHILDREN; RISK; FARM; LIPOPOLYSACCHARIDE; RECOGNITION; EXPRESSION	The pre- and postnatal environment may represent a window of opportunity for allergy and asthma prevention, and the hygiene hypothesis implies that microbial agents may play an important role in this regard. Using the cowshed-derived bacterium Acinetobacter lwoffii F78 together with a mouse model of experimental allergic airway inflammation, this study investigated the hygiene hypothesis, maternal (prenatal) microbial exposure, and the involvement of Toll-like receptor (TLR) signaling in prenatal protection from asthma. Maternal intranasal exposure to A. lwoffii F78 protected against the development of experimental asthma in the progeny. Maternally, A. lwoffii F78 exposure resulted in a transient increase in lung and serum proinflammatory cytokine production and up-regulation of lung TLR messenger RNA. Conversely, suppression of TLRs was observed in placental tissue. To investigate further, the functional relevance of maternal TLR signaling was tested in TLR2/3/4/7/9(-/-) knockout mice. The asthma-preventive effect was completely abolished in heterozygous offspring from A. lwoffii F78-treated TLR2/3/4/7/9(-/-) homozygous mother mice. Furthermore, the mild local and systemic inflammatory response was also absent in these A. lwoffii F78-exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny.	32	161	2009	9	10.1084/jem.20090845	Immunology; Research & Experimental Medicine
Regulatory T Cells in Asthma. Asthma is characterized by T helper cell 2 (Th2) type inflammation, leading to airway hyperresponsiveness and tissue remodeling. Th2 cell-driven inflammation is likely to represent an abnormal response to harmless airborne particles. These reactions are normally suppressed by regulatory T cells, which maintain airway tolerance. The anti-inflammatory cytokine IL-10 is likely to play a central role. The role of the cytokine transforming growth factor beta (TGF-beta) is more complex, with evidence for immune suppression and remodeling in the airways. In asthmatic individuals there is a breakdown in these regulatory mechanisms. There is emerging evidence that early life events, including exposure to allergen and infections, are critical in programming effective regulatory pathways to maintain pulmonary homeostasis. In this review we examine the clinical and experimental evidence for T regulatory cell function in the lung and discuss the events that might influence the functioning of these cells. Ultimately, the ability to enhance regulatory function in affected individuals may represent an effective treatment for asthma.. induced airway hyperreactivity| vitamin-d supplementation| tgf-beta| immune dysregulation| inhaled antigen| allergic-asthma| dendritic cells| in-vivo| peptide immunotherapy| alveolar macrophages.	SEP 18-2009	induced airway hyperreactivity| vitamin-d supplementation| tgf-beta| immune dysregulation| inhaled antigen| allergic-asthma| dendritic cells| in-vivo| peptide immunotherapy| alveolar macrophages	Lloyd, CM; Hawrylowicz, CM	Regulatory T Cells in Asthma		IMMUNITY		INDUCED AIRWAY HYPERREACTIVITY; VITAMIN-D SUPPLEMENTATION; TGF-BETA; IMMUNE DYSREGULATION; INHALED ANTIGEN; ALLERGIC-ASTHMA; DENDRITIC CELLS; IN-VIVO; PEPTIDE IMMUNOTHERAPY; ALVEOLAR MACROPHAGES	Asthma is characterized by T helper cell 2 (Th2) type inflammation, leading to airway hyperresponsiveness and tissue remodeling. Th2 cell-driven inflammation is likely to represent an abnormal response to harmless airborne particles. These reactions are normally suppressed by regulatory T cells, which maintain airway tolerance. The anti-inflammatory cytokine IL-10 is likely to play a central role. The role of the cytokine transforming growth factor beta (TGF-beta) is more complex, with evidence for immune suppression and remodeling in the airways. In asthmatic individuals there is a breakdown in these regulatory mechanisms. There is emerging evidence that early life events, including exposure to allergen and infections, are critical in programming effective regulatory pathways to maintain pulmonary homeostasis. In this review we examine the clinical and experimental evidence for T regulatory cell function in the lung and discuss the events that might influence the functioning of these cells. Ultimately, the ability to enhance regulatory function in affected individuals may represent an effective treatment for asthma.	117	161	2009	12	10.1016/j.immuni.2009.08.007	Immunology
A review of the evidence for the medical home for children with special health care needs. CONTEXT. The receipt of health care in a medical home is increasingly touted as a fundamental basis for improved care for persons with chronic conditions, yet the evidence for this claim has not been systematically assessed. OBJECTIVE. Our goal was to determine the evidence for the federal Maternal and Child Health Bureau recommendation that children with special health care needs receive ongoing comprehensive care within a medical home. METHODS. We searched the nursing and medical literature, references of selected articles, and requested expert recommendations. Search terms included children with special health care needs, medical home-related interventions, and health-related outcomes. Articles that met defined criteria (eg, children with special health care needs, United States-based, quantitative) were selected. We extracted data, including design, population characteristics, sample size, intervention, and findings from each article. RESULTS. We selected 33 articles that reported on 30 distinct studies, 10 of which were comparison-group studies. None of the studies examined the medical home in its entirety. Although tempered by weak designs, inconsistent definitions and extent of medical home attributes, and inconsistent outcome measures, the preponderance of evidence supported a positive relationship between the medical home and desired outcomes, such as better health status, timeliness of care, family centeredness, and improved family functioning. CONCLUSIONS. The evidence provides moderate support for the hypothesis that medical homes provide improved health-related outcomes for children with special health care needs. Additional studies with comparison groups encompassing all or most of the attributes of the medical home need to be undertaken.. medical home| special needs children| systematic review| family-centered care|pediatric-asthma-care| outcomes-research-team| quality improvement| patient-outcomes| chronic illness| coordinated care| national-survey| family| emergency| access.	OCT-2008	medical home| special needs children| systematic review| family-centered care|pediatric-asthma-care| outcomes-research-team| quality improvement| patient-outcomes| chronic illness| coordinated care| national-survey| family| emergency| access	Homer, CJ; Klatka, K; Romm, D; Kuhlthau, K; Bloom, S; Newacheck, P; Van Cleave, J; Perrin, JM	A review of the evidence for the medical home for children with special health care needs		PEDIATRICS	medical home; special needs children; systematic review; family-centered care	PEDIATRIC-ASTHMA-CARE; OUTCOMES-RESEARCH-TEAM; QUALITY IMPROVEMENT; PATIENT-OUTCOMES; CHRONIC ILLNESS; COORDINATED CARE; NATIONAL-SURVEY; FAMILY; EMERGENCY; ACCESS	CONTEXT. The receipt of health care in a medical home is increasingly touted as a fundamental basis for improved care for persons with chronic conditions, yet the evidence for this claim has not been systematically assessed. OBJECTIVE. Our goal was to determine the evidence for the federal Maternal and Child Health Bureau recommendation that children with special health care needs receive ongoing comprehensive care within a medical home. METHODS. We searched the nursing and medical literature, references of selected articles, and requested expert recommendations. Search terms included children with special health care needs, medical home-related interventions, and health-related outcomes. Articles that met defined criteria (eg, children with special health care needs, United States-based, quantitative) were selected. We extracted data, including design, population characteristics, sample size, intervention, and findings from each article. RESULTS. We selected 33 articles that reported on 30 distinct studies, 10 of which were comparison-group studies. None of the studies examined the medical home in its entirety. Although tempered by weak designs, inconsistent definitions and extent of medical home attributes, and inconsistent outcome measures, the preponderance of evidence supported a positive relationship between the medical home and desired outcomes, such as better health status, timeliness of care, family centeredness, and improved family functioning. CONCLUSIONS. The evidence provides moderate support for the hypothesis that medical homes provide improved health-related outcomes for children with special health care needs. Additional studies with comparison groups encompassing all or most of the attributes of the medical home need to be undertaken.	58	161	2008	16	10.1542/peds.2007-3762	Pediatrics
Community-based participatory research: Lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research. Over the past several decades there has been growing evidence of the increase in incidence rates, morbidity, and mortality for a number of health problems experienced by children. The causation and aggravation of these problems are complex and multifactorial. The burden of these health problems and environmental exposures is borne disproportionately by children from low-income communities and communities of color. Researchers and funding institutions have called for increased attention to the complex issues that affect the health of children living in marginalized communities-and communities more broadly and have suggested greater community involvement in processes that shape research and intervention approaches, for example, through community-based participatory research (CBPR) partnerships among academic, health services, public health, and community-based organizations. Centers for Children's Environmental Health and Disease Prevention Research (Children's Centers) funded by the National Institute of Environmental Health Sciences and U.S. Environmental Protection Agency, were required to include a CBPR project. The purpose of this article is to provide a definition and set of CBPR principles, to describe the rationale for and major benefits of using this approach, to draw on the experiences of six of the Children's Centers in using CBPR, and to provide lessons learned and recommendations for how to successfully establish and maintain CBPR partnerships aimed at enhancing our understanding and addressing the multiple determinants of children's health.. children's health| collaborative research| community-based participatory research| partnership|particulate air-pollution| inner-city children| public-health| pesticide exposure| tobacco-smoke| asthma| partnership| association| population| pollutants.	OCT-2005	children's health| collaborative research| community-based participatory research| partnership|particulate air-pollution| inner-city children| public-health| pesticide exposure| tobacco-smoke| asthma| partnership| association| population| pollutants	Israel, BA; Parker, EA; Rowe, Z; Salvatore, A; Minkler, M; Lopez, J; Butz, A; Mosley, A; Coates, L; Lambert, G; Potito, PA; Brenner, B; Rivera, M; Romero, H; Thompson, B; Coronado, G; Halstead, S	Community-based participatory research: Lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research		ENVIRONMENTAL HEALTH PERSPECTIVES	children's health; collaborative research; community-based participatory research; partnership	PARTICULATE AIR-POLLUTION; INNER-CITY CHILDREN; PUBLIC-HEALTH; PESTICIDE EXPOSURE; TOBACCO-SMOKE; ASTHMA; PARTNERSHIP; ASSOCIATION; POPULATION; POLLUTANTS	Over the past several decades there has been growing evidence of the increase in incidence rates, morbidity, and mortality for a number of health problems experienced by children. The causation and aggravation of these problems are complex and multifactorial. The burden of these health problems and environmental exposures is borne disproportionately by children from low-income communities and communities of color. Researchers and funding institutions have called for increased attention to the complex issues that affect the health of children living in marginalized communities-and communities more broadly and have suggested greater community involvement in processes that shape research and intervention approaches, for example, through community-based participatory research (CBPR) partnerships among academic, health services, public health, and community-based organizations. Centers for Children's Environmental Health and Disease Prevention Research (Children's Centers) funded by the National Institute of Environmental Health Sciences and U.S. Environmental Protection Agency, were required to include a CBPR project. The purpose of this article is to provide a definition and set of CBPR principles, to describe the rationale for and major benefits of using this approach, to draw on the experiences of six of the Children's Centers in using CBPR, and to provide lessons learned and recommendations for how to successfully establish and maintain CBPR partnerships aimed at enhancing our understanding and addressing the multiple determinants of children's health.	47	161	2005	9	10.1289/ehp.7675	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
The role of air pollution in asthma and other pediatric morbidities. A growing body of research supports the role of outdoor air pollutants in acutely aggravating chronic diseases in children, and suggests that the pollutants may have a role in the development of these diseases. This article reviews the biologic basis of children's unique vulnerability to highly prevalent outdoor air pollutants, with a special focus on ozone, respirable particulate matter (PM2.5 [< 2.5 mu m in diameter] and PM10 [< 10 mu m in diameter]), lead, sulfur dioxide, carbon monoxide, and nitrogen oxides. We also summarize understanding regarding health effects and molecular mechanisms of action. Practitioners can significantly reduce morbidity in children and other vulnerable populations by advising families to minimize pollutant exposures to children with asthma, or at a broader level by educating policymakers about the need to act to reduce pollutant emissions. Management of children with asthma must expand beyond preventing exposures to agents that directly cause allergic reactions (and therefore can be diagnosed by means of skin tests) and must focus more attention on agents that cause a broad spectrum of nonspecific, generalized inflammation, such as air pollution.. asthma| particulate matter| lead| sulfur dioxide| carbon monoxide| nitrogen oxides| children's environmental health|diesel exhaust particles| low-birth-weight| emergency-room visits| trade-center disaster| southern california| childhood asthma| infant-mortality| sulfur-dioxide| respiratory symptoms| hospital admissions.	APR-2005	asthma| particulate matter| lead| sulfur dioxide| carbon monoxide| nitrogen oxides| children's environmental health|diesel exhaust particles| low-birth-weight| emergency-room visits| trade-center disaster| southern california| childhood asthma| infant-mortality| sulfur-dioxide| respiratory symptoms| hospital admissions	Trasande, L; Thurston, GD	The role of air pollution in asthma and other pediatric morbidities		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; particulate matter; lead; sulfur dioxide; carbon monoxide; nitrogen oxides; children's environmental health	DIESEL EXHAUST PARTICLES; LOW-BIRTH-WEIGHT; EMERGENCY-ROOM VISITS; TRADE-CENTER DISASTER; SOUTHERN CALIFORNIA; CHILDHOOD ASTHMA; INFANT-MORTALITY; SULFUR-DIOXIDE; RESPIRATORY SYMPTOMS; HOSPITAL ADMISSIONS	A growing body of research supports the role of outdoor air pollutants in acutely aggravating chronic diseases in children, and suggests that the pollutants may have a role in the development of these diseases. This article reviews the biologic basis of children's unique vulnerability to highly prevalent outdoor air pollutants, with a special focus on ozone, respirable particulate matter (PM2.5 [< 2.5 mu m in diameter] and PM10 [< 10 mu m in diameter]), lead, sulfur dioxide, carbon monoxide, and nitrogen oxides. We also summarize understanding regarding health effects and molecular mechanisms of action. Practitioners can significantly reduce morbidity in children and other vulnerable populations by advising families to minimize pollutant exposures to children with asthma, or at a broader level by educating policymakers about the need to act to reduce pollutant emissions. Management of children with asthma must expand beyond preventing exposures to agents that directly cause allergic reactions (and therefore can be diagnosed by means of skin tests) and must focus more attention on agents that cause a broad spectrum of nonspecific, generalized inflammation, such as air pollution.	102	161	2005	11	10.1016/j.jaci.2005.01.056	Allergy; Immunology
House dust endotoxin and allergic sensitization in children. A higher exposure to endotoxin was hypothesized to contribute to lower prevalence of allergic sensitization and hay fever in children growing up on a farm. We studied the association between house dust endotoxin and allergic sensitization. We randomly selected 740 children, aged between 5 and 10 years, from a group of children who participated in two cross-sectional surveys performed in Saxony-Anhalt, Germany, from 1992 to 1993 and from 1995 to 1996, such that 50% of the children were atopic or had a diagnosis of asthma. From 1996 to 1998, we collected living-room floor dust in the homes of 454 of these children (61%). The content of endotoxin in house dust was quantified using a chromogenic kinetic limulus amoebocyte lysate test and was related with health outcomes measured in the preceding cross-sectional surveys. Multiple logistic regression analyses adjusted for place of residence, sex, age, parental education, parental atopy, and pet ownership showed a negative association between exposure to endotoxin and sensitization to one or more allergens (aOR [95% CI] 0.95 [0.83; 1.10]) and two or more allergens (aOR [95% CI] 0.80 [0.67, 0.97]) using 0.35 kU/L as the cutoff value for sensitization. The protective effect was strengthened with increasing degree of sensitization. In conclusion, exposure to higher levels of house dust endotoxin is associated with lower prevalence of allergic sensitization in children.. endotoxin| house dust| atopy| school children|hay-fever| early-life| exposure| asthma| atopy| childhood| farm| risk| cat| environment.	OCT 1-2002	endotoxin| house dust| atopy| school children|hay-fever| early-life| exposure| asthma| atopy| childhood| farm| risk| cat| environment	Gehring, U; Bischof, W; Fahlbusch, B; Wichmann, HE; Heinrich, J	House dust endotoxin and allergic sensitization in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	endotoxin; house dust; atopy; school children	HAY-FEVER; EARLY-LIFE; EXPOSURE; ASTHMA; ATOPY; CHILDHOOD; FARM; RISK; CAT; ENVIRONMENT	A higher exposure to endotoxin was hypothesized to contribute to lower prevalence of allergic sensitization and hay fever in children growing up on a farm. We studied the association between house dust endotoxin and allergic sensitization. We randomly selected 740 children, aged between 5 and 10 years, from a group of children who participated in two cross-sectional surveys performed in Saxony-Anhalt, Germany, from 1992 to 1993 and from 1995 to 1996, such that 50% of the children were atopic or had a diagnosis of asthma. From 1996 to 1998, we collected living-room floor dust in the homes of 454 of these children (61%). The content of endotoxin in house dust was quantified using a chromogenic kinetic limulus amoebocyte lysate test and was related with health outcomes measured in the preceding cross-sectional surveys. Multiple logistic regression analyses adjusted for place of residence, sex, age, parental education, parental atopy, and pet ownership showed a negative association between exposure to endotoxin and sensitization to one or more allergens (aOR [95% CI] 0.95 [0.83; 1.10]) and two or more allergens (aOR [95% CI] 0.80 [0.67, 0.97]) using 0.35 kU/L as the cutoff value for sensitization. The protective effect was strengthened with increasing degree of sensitization. In conclusion, exposure to higher levels of house dust endotoxin is associated with lower prevalence of allergic sensitization in children.	35	161	2002	6	10.1164/rccm.200203-256OC	General & Internal Medicine; Respiratory System
The prevalence of allergy to egg: a population-based study in young children. Background: The aim of the present study was to estimate the prevalence of adverse reactions to egg, as population-based prevalence estimates based on objective diagnostic procedures are lacking. Methods: The parents of 2721 children in a population-based birth cohort completed questionnaires on the occurrence of any reaction to food at 12, 18, and 24 months of age. Children with parentally reported reactions to eggs at the age of 2 years were selected for further examination. A stepwise diagnostic procedure was developed that included diet trials at home, skin prick tests, and open and double-blind, placebo-controlled food challenges. The mean age of the children at the time of the examination was 2.5 years (CI 2.5-2.6). A sample of children without perceived reactions to egg was also selected for assessment of unrecognized reactions. Results: The estimated point prevalence of allergy to egg in children aged 2 1/2 years was 1.6% (CI 1.3-2.0%), with an upper estimate of the cumulative incidence by this age calculated roughly at 2.6% (CI 1.6-3.6). Almost all reactions were IgE mediated. In general, two-thirds of the parentally perceived reactions were verified. However, the positive predictive value of a parentally perceived reaction depended on the number of times it had been reported, and increased from 50% to 100%, for reactions reported one and three times, respectively. Unrecognized reactions were infrequent. Conclusions: This study confirms that allergy to egg is frequent in a child population.. adverse reactions| dbpcfc| egg| egg hypersensitivity| epidemiology| food hypersensitivity| prevalence| prospective|cows milk allergy| controlled food challenges| skin-test reactivity| double-blind| clinical manifestations| atopic-dermatitis| adverse reactions| hypersensitivity| childhood| infancy.	MAY-2001	adverse reactions| dbpcfc| egg| egg hypersensitivity| epidemiology| food hypersensitivity| prevalence| prospective|cows milk allergy| controlled food challenges| skin-test reactivity| double-blind| clinical manifestations| atopic-dermatitis| adverse reactions| hypersensitivity| childhood| infancy	Eggesbo, M; Botten, G; Halvorsen, R; Magnus, P	The prevalence of allergy to egg: a population-based study in young children		ALLERGY	adverse reactions; DBPCFC; egg; egg hypersensitivity; epidemiology; food hypersensitivity; prevalence; prospective	COWS MILK ALLERGY; CONTROLLED FOOD CHALLENGES; SKIN-TEST REACTIVITY; DOUBLE-BLIND; CLINICAL MANIFESTATIONS; ATOPIC-DERMATITIS; ADVERSE REACTIONS; HYPERSENSITIVITY; CHILDHOOD; INFANCY	Background: The aim of the present study was to estimate the prevalence of adverse reactions to egg, as population-based prevalence estimates based on objective diagnostic procedures are lacking. Methods: The parents of 2721 children in a population-based birth cohort completed questionnaires on the occurrence of any reaction to food at 12, 18, and 24 months of age. Children with parentally reported reactions to eggs at the age of 2 years were selected for further examination. A stepwise diagnostic procedure was developed that included diet trials at home, skin prick tests, and open and double-blind, placebo-controlled food challenges. The mean age of the children at the time of the examination was 2.5 years (CI 2.5-2.6). A sample of children without perceived reactions to egg was also selected for assessment of unrecognized reactions. Results: The estimated point prevalence of allergy to egg in children aged 2 1/2 years was 1.6% (CI 1.3-2.0%), with an upper estimate of the cumulative incidence by this age calculated roughly at 2.6% (CI 1.6-3.6). Almost all reactions were IgE mediated. In general, two-thirds of the parentally perceived reactions were verified. However, the positive predictive value of a parentally perceived reaction depended on the number of times it had been reported, and increased from 50% to 100%, for reactions reported one and three times, respectively. Unrecognized reactions were infrequent. Conclusions: This study confirms that allergy to egg is frequent in a child population.	36	161	2001	9	10.1034/j.1398-9995.2001.056005403.x	Allergy; Immunology
Patients with chronic obstructive pulmonary disease are at increased risk of death associated with urban particle air pollution: A case-crossover analysis. The authors assessed the acute association between particulate air pollution and mortality among subjects suffering from chronic obstructive pulmonary disease by using a case-crossover analysis. This design avoided the common concerns about the methods used to assess the acute effects of air pollution. The 1,845 men and the 460 women included were residents of Barcelona, Spain, who were over age 35 years, had died during the period 1990-1995, and had visited emergency rooms because of a chronic obstructive pulmonary disease exacerbation during the period 1985-1989. Particle levels (measured as black smoke at the city monitoring stations) were associated with mortality for all causes (odds ratio (OR) for an increase of 20 mu g/m(3), the interquartile change, adjusted for temperature, humidity, and influenza = 1.112, 95 percent confidence interval (CI): 1.017, 1.215). The association was stronger for respiratory causes (OR = 1.182, 95 percent CI: 1.025, 1.365), but was not significant for cardiovascular causes (OR = 1.077, 95 percent CI: 0.917, 1.264). Older women, patients admitted to intensive care units, and patients with a higher rate of emergency room visits were at greater risk of dying associated with black smoke. The results reinforced the deleterious role of urban pollution and provided information on factors possibly conferring susceptibility to the acute role of air pollution.. air pollution| lung diseases| obstructive| mortality|emergency room admissions| hospital admissions| particulate matter| european cities| aphea project| mortality| asthma| deposition| gender.	JAN 1-2000	air pollution| lung diseases| obstructive| mortality|emergency room admissions| hospital admissions| particulate matter| european cities| aphea project| mortality| asthma| deposition| gender	Sunyer, J; Schwartz, J; Tobias, A; Macfarlane, D; Garcia, J; Anto, JM	Patients with chronic obstructive pulmonary disease are at increased risk of death associated with urban particle air pollution: A case-crossover analysis		AMERICAN JOURNAL OF EPIDEMIOLOGY	air pollution; lung diseases; obstructive; mortality	EMERGENCY ROOM ADMISSIONS; HOSPITAL ADMISSIONS; PARTICULATE MATTER; EUROPEAN CITIES; APHEA PROJECT; MORTALITY; ASTHMA; DEPOSITION; GENDER	The authors assessed the acute association between particulate air pollution and mortality among subjects suffering from chronic obstructive pulmonary disease by using a case-crossover analysis. This design avoided the common concerns about the methods used to assess the acute effects of air pollution. The 1,845 men and the 460 women included were residents of Barcelona, Spain, who were over age 35 years, had died during the period 1990-1995, and had visited emergency rooms because of a chronic obstructive pulmonary disease exacerbation during the period 1985-1989. Particle levels (measured as black smoke at the city monitoring stations) were associated with mortality for all causes (odds ratio (OR) for an increase of 20 mu g/m(3), the interquartile change, adjusted for temperature, humidity, and influenza = 1.112, 95 percent confidence interval (CI): 1.017, 1.215). The association was stronger for respiratory causes (OR = 1.182, 95 percent CI: 1.025, 1.365), but was not significant for cardiovascular causes (OR = 1.077, 95 percent CI: 0.917, 1.264). Older women, patients admitted to intensive care units, and patients with a higher rate of emergency room visits were at greater risk of dying associated with black smoke. The results reinforced the deleterious role of urban pollution and provided information on factors possibly conferring susceptibility to the acute role of air pollution.	35	161	2000	7		Public, Environmental & Occupational Health
The immunology of asthma. Asthma is a common disease that affects 300 million people worldwide. Given the large number of eosinophils in the airways of people with mild asthma, and verified by data from murine models, asthma was long considered the hallmark T helper type 2 (T(H)2) disease of the airways. It is now known that some asthmatic inflammation is neutrophilic, controlled by the T(H)17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) acting together with basophils. Here we discuss results from in-depth molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans and describe the extraordinary heterogeneity of asthma.. innate lymphoid-cells| allergic airway inflammation| house-dust mite| plasmacytoid dendritic cells| regulatory t-cells| fc-epsilon-ri| natural helper-cells| thymic stromal lymphopoietin| respiratory viral-infection| affinity ige receptor.	JAN-2015	innate lymphoid-cells| allergic airway inflammation| house-dust mite| plasmacytoid dendritic cells| regulatory t-cells| fc-epsilon-ri| natural helper-cells| thymic stromal lymphopoietin| respiratory viral-infection| affinity ige receptor	Lambrecht, BN; Hammad, H	The immunology of asthma		NATURE IMMUNOLOGY		INNATE LYMPHOID-CELLS; ALLERGIC AIRWAY INFLAMMATION; HOUSE-DUST MITE; PLASMACYTOID DENDRITIC CELLS; REGULATORY T-CELLS; FC-EPSILON-RI; NATURAL HELPER-CELLS; THYMIC STROMAL LYMPHOPOIETIN; RESPIRATORY VIRAL-INFECTION; AFFINITY IGE RECEPTOR	Asthma is a common disease that affects 300 million people worldwide. Given the large number of eosinophils in the airways of people with mild asthma, and verified by data from murine models, asthma was long considered the hallmark T helper type 2 (T(H)2) disease of the airways. It is now known that some asthmatic inflammation is neutrophilic, controlled by the T(H)17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) acting together with basophils. Here we discuss results from in-depth molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans and describe the extraordinary heterogeneity of asthma.	185	160	2015	12	10.1038/ni.3049	Immunology
Near-Roadway Air Quality: Synthesizing the Findings from Real-World Data. Despite increasing regulatory attention and literature linking roadside air pollution to health outcomes, studies on near roadway air quality have not yet been well synthesized. We employ data collected from 1978 as reported in 41 roadside monitoring studies, encompassing more than 700 air pollutant concentration measurements, published as of June 2008. Two types of normalization, background and edge-of-road, were applied to the observed concentrations. Local regression models were specified to the concentration-distance relationship and analysis of variance was used to determine the statistical significance of trends. Using an edge-of-road normalization, almost all pollutants decay to background by 115-570 m from the edge of road; using the more standard background normalization, almost all pollutants decay to background by 160-570 m from the edge of road. Differences between the normalization methods arose due to the likely bias inherent in background normalization, since some reported background values tend to underpredict (be lower than) actual background. Changes in pollutant concentrations with increasing distance from the road fell into one of three groups: at least a 50% decrease in peak/edge-of-road concentration by 150 m, followed by consistent but gradual decay toward background (e.g., carbon monoxide, some uttrafine particulate matter number concentrations); consistent decay or change over the entire distance range (e.g., benzene, nitrogen dioxide); or no trend with distance (e.g., particulate matter mass concentrations).. childrens respiratory health| airborne particulate matter| scale spatial variability| ultrafine particles| size distribution| nitrogen-dioxide| childhood asthma| major highway| traffic density| los-angeles.	JUL 15-2010	childrens respiratory health| airborne particulate matter| scale spatial variability| ultrafine particles| size distribution| nitrogen-dioxide| childhood asthma| major highway| traffic density| los-angeles	Karner, AA; Eisinger, DS; Niemeier, DA	Near-Roadway Air Quality: Synthesizing the Findings from Real-World Data		ENVIRONMENTAL SCIENCE & TECHNOLOGY		CHILDRENS RESPIRATORY HEALTH; AIRBORNE PARTICULATE MATTER; SCALE SPATIAL VARIABILITY; ULTRAFINE PARTICLES; SIZE DISTRIBUTION; NITROGEN-DIOXIDE; CHILDHOOD ASTHMA; MAJOR HIGHWAY; TRAFFIC DENSITY; LOS-ANGELES	Despite increasing regulatory attention and literature linking roadside air pollution to health outcomes, studies on near roadway air quality have not yet been well synthesized. We employ data collected from 1978 as reported in 41 roadside monitoring studies, encompassing more than 700 air pollutant concentration measurements, published as of June 2008. Two types of normalization, background and edge-of-road, were applied to the observed concentrations. Local regression models were specified to the concentration-distance relationship and analysis of variance was used to determine the statistical significance of trends. Using an edge-of-road normalization, almost all pollutants decay to background by 115-570 m from the edge of road; using the more standard background normalization, almost all pollutants decay to background by 160-570 m from the edge of road. Differences between the normalization methods arose due to the likely bias inherent in background normalization, since some reported background values tend to underpredict (be lower than) actual background. Changes in pollutant concentrations with increasing distance from the road fell into one of three groups: at least a 50% decrease in peak/edge-of-road concentration by 150 m, followed by consistent but gradual decay toward background (e.g., carbon monoxide, some uttrafine particulate matter number concentrations); consistent decay or change over the entire distance range (e.g., benzene, nitrogen dioxide); or no trend with distance (e.g., particulate matter mass concentrations).	74	160	2010	11	10.1021/es100008x	Engineering; Environmental Sciences & Ecology
Household peanut consumption as a risk factor for the development of peanut allergy. Background: Most children with peanut allergy (PA) react on first known oral exposure to peanut. Recent data suggest cutaneous exposure as a route of sensitization. Objectives: This study aimed to establish the relevant route of peanut exposure in the development of allergy. Methods: Questionnaires were administered to children with PA and to high-risk controls (with egg allergy) and controls without allergy. Questionnaires were completed before subjects were aware of their PA status, avoiding recall bias. Questionnaires recorded maternal peanut consumption during pregnancy, breast-feeding, and the first year of life. Peanut consumption was determined among all household members, allowing quantification of environmental household exposure (household peanut). Results: Median weekly household peanut in the 133 PA cases was significantly elevated (18.8 g) compared with 150 controls without allergy (6.9 g) and 160 high-risk controls (1.9 g). There were no differences in infant peanut consumption between groups. Differences in maternal peanut consumption during pregnancy (and lactation) were significant but become nonsignificant after adjusting for household peanut. A dose-response relationship was observed between environmental (nonoral) peanut exposure and the development of PA, which was strongest for peanut butter. Early oral exposure to peanut in infants with high environmental peanut exposure may have had a protective effect against the development of PA. Conclusions: High levels of environmental exposure to peanut during infancy appear to promote sensitization, whereas low levels may be protective in atopic children. No effect of maternal peanut consumption during pregnancy or lactation is observed, supporting the hypothesis that peanut sensitization occurs as a result of environmental exposure. (J Allergy Clin Immunol 2009;123:417-23.). allergy| children| food allergy| peanut allergy| sensitization| peanut consumption| cutaneous exposure| environmental exposure|food challenges| nut allergy| follow-up| children| exposure| antigen| ige| avoidance| childhood| features.	FEB-2009	allergy| children| food allergy| peanut allergy| sensitization| peanut consumption| cutaneous exposure| environmental exposure|food challenges| nut allergy| follow-up| children| exposure| antigen| ige| avoidance| childhood| features	Fox, AT; Sasieni, P; du Toit, G; Syed, H; Lack, G	Household peanut consumption as a risk factor for the development of peanut allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergy; children; food allergy; peanut allergy; sensitization; peanut consumption; cutaneous exposure; environmental exposure	FOOD CHALLENGES; NUT ALLERGY; FOLLOW-UP; CHILDREN; EXPOSURE; ANTIGEN; IGE; AVOIDANCE; CHILDHOOD; FEATURES	Background: Most children with peanut allergy (PA) react on first known oral exposure to peanut. Recent data suggest cutaneous exposure as a route of sensitization. Objectives: This study aimed to establish the relevant route of peanut exposure in the development of allergy. Methods: Questionnaires were administered to children with PA and to high-risk controls (with egg allergy) and controls without allergy. Questionnaires were completed before subjects were aware of their PA status, avoiding recall bias. Questionnaires recorded maternal peanut consumption during pregnancy, breast-feeding, and the first year of life. Peanut consumption was determined among all household members, allowing quantification of environmental household exposure (household peanut). Results: Median weekly household peanut in the 133 PA cases was significantly elevated (18.8 g) compared with 150 controls without allergy (6.9 g) and 160 high-risk controls (1.9 g). There were no differences in infant peanut consumption between groups. Differences in maternal peanut consumption during pregnancy (and lactation) were significant but become nonsignificant after adjusting for household peanut. A dose-response relationship was observed between environmental (nonoral) peanut exposure and the development of PA, which was strongest for peanut butter. Early oral exposure to peanut in infants with high environmental peanut exposure may have had a protective effect against the development of PA. Conclusions: High levels of environmental exposure to peanut during infancy appear to promote sensitization, whereas low levels may be protective in atopic children. No effect of maternal peanut consumption during pregnancy or lactation is observed, supporting the hypothesis that peanut sensitization occurs as a result of environmental exposure. (J Allergy Clin Immunol 2009;123:417-23.)	30	160	2009	7	10.1016/j.jaci.2008.12.014	Allergy; Immunology
"Genome-Wide Scan on Total Serum IgE Levels Identifies FCER1A as Novel Susceptibility Locus. High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85 x 10(-20) and 7.08 x 10(-19) in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78 x 10(-4) and P = 1.95 x 10(-3)). The ""top'' SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28 x 10(-7) -4.46 x 10(-8)) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels.. immunoglobulin-e concentrations| th2 cytokine locus| epsilon-ri-beta| control region| japanese population| atopic-dermatitis| asthma| association| gene| disease."	AUG-2008	immunoglobulin-e concentrations| th2 cytokine locus| epsilon-ri-beta| control region| japanese population| atopic-dermatitis| asthma| association| gene| disease	Weidinger, S; Gieger, C; Rodriguez, E; Baurecht, H; Mempel, M; Klopp, N; Gohlke, H; Wagenpfeil, S; Ollert, M; Ring, J; Behrendt, H; Heinrich, J; Novak, N; Bieber, T; Kraemer, U; Berdel, D; von Berg, A; Bauer, CP; Herbarth, O; Koletzko, S; Prokisch, H; Mehta, D; Meitinger, T; Depner, M; von Mutius, E; Liang, L; Moffatt, M; Cookson, W; Kabesch, M; Wichmann, HE; Illig, T	Genome-Wide Scan on Total Serum IgE Levels Identifies FCER1A as Novel Susceptibility Locus		PLOS GENETICS		IMMUNOGLOBULIN-E CONCENTRATIONS; TH2 CYTOKINE LOCUS; EPSILON-RI-BETA; CONTROL REGION; JAPANESE POPULATION; ATOPIC-DERMATITIS; ASTHMA; ASSOCIATION; GENE; DISEASE	"High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85 x 10(-20) and 7.08 x 10(-19) in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78 x 10(-4) and P = 1.95 x 10(-3)). The ""top'' SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28 x 10(-7) -4.46 x 10(-8)) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels."	41	160	2008	9	10.1371/journal.pgen.1000166	Genetics & Heredity
Palladium - A review of exposure and effects to human health. Palladium is a metal the output and use of which has more than doubled in the past ten years. It is used in dental appliances, chemical catalysts, electrical appliances and jewellery, but the greatest increase in I'd demand has been in automotive emission control catalysts. Studies on I'd concentrations in ancient ice and recent snow samples reflect the increase in mining, smelting and use of palladium in the last decades. Increases of palladium in the environment have been shown in air and dust samples. There is no data as yet available to assess the effect of this exposure. A major source of health concern is the sensitization risk of Pd as very low doses are sufficient to cause allergic reactions in susceptible individuals. Persons with known nickel allergy may be especially susceptible. Workers occupationally exposed to Pd include miners, dental technicians and chemical workers. The latter are exposed mainly to I'd salts several of which may cause primary skin and eye irritations. It. is advised that persons with known Pd allergy should not work with I'd compounds. The general population may come into contact with palladium mainly through mucosal contact with dental restorations and jewellery containing palladium and possibly via emissions from Pd catalysts. Protection of the public from related adverse effects may be achieved by the use of alloys with high corrosion stability and thus minimal release of palladium. In general, in dental patients who are sensitive to Pd, restorations using Pd-containing materials should not be used although I'd has been used without allergic effects in some of these individuals. Further, those patients who have an allergy to nickel should be informed that use of Pd-containing dental materials may cause I'd allergy, though this risk appears to be low.. palladium| exposure| health effects| dental alloys| sensitization| nickel| allergy| auto catalytic converters| catalysts| lewellery|platinum-group elements| dental-casting alloys| cell-culture medium| contact-dermatitis| cross-reactivity| in-vitro| allergy diagnosis| metal-compounds| nickel sulfate| exhaust fumes.	OCT-2002	palladium| exposure| health effects| dental alloys| sensitization| nickel| allergy| auto catalytic converters| catalysts| lewellery|platinum-group elements| dental-casting alloys| cell-culture medium| contact-dermatitis| cross-reactivity| in-vitro| allergy diagnosis| metal-compounds| nickel sulfate| exhaust fumes	Kielhorn, J; Melber, C; Keller, D; Mangelsdorf, I	Palladium - A review of exposure and effects to human health		INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH	palladium; exposure; health effects; dental alloys; sensitization; nickel; allergy; auto catalytic converters; catalysts; lewellery	PLATINUM-GROUP ELEMENTS; DENTAL-CASTING ALLOYS; CELL-CULTURE MEDIUM; CONTACT-DERMATITIS; CROSS-REACTIVITY; IN-VITRO; ALLERGY DIAGNOSIS; METAL-COMPOUNDS; NICKEL SULFATE; EXHAUST FUMES	Palladium is a metal the output and use of which has more than doubled in the past ten years. It is used in dental appliances, chemical catalysts, electrical appliances and jewellery, but the greatest increase in I'd demand has been in automotive emission control catalysts. Studies on I'd concentrations in ancient ice and recent snow samples reflect the increase in mining, smelting and use of palladium in the last decades. Increases of palladium in the environment have been shown in air and dust samples. There is no data as yet available to assess the effect of this exposure. A major source of health concern is the sensitization risk of Pd as very low doses are sufficient to cause allergic reactions in susceptible individuals. Persons with known nickel allergy may be especially susceptible. Workers occupationally exposed to Pd include miners, dental technicians and chemical workers. The latter are exposed mainly to I'd salts several of which may cause primary skin and eye irritations. It. is advised that persons with known Pd allergy should not work with I'd compounds. The general population may come into contact with palladium mainly through mucosal contact with dental restorations and jewellery containing palladium and possibly via emissions from Pd catalysts. Protection of the public from related adverse effects may be achieved by the use of alloys with high corrosion stability and thus minimal release of palladium. In general, in dental patients who are sensitive to Pd, restorations using Pd-containing materials should not be used although I'd has been used without allergic effects in some of these individuals. Further, those patients who have an allergy to nickel should be informed that use of Pd-containing dental materials may cause I'd allergy, though this risk appears to be low.	137	160	2002	16	10.1078/1438-4639-00180	Public, Environmental & Occupational Health; Infectious Diseases
Bacterial infection causes stress-induced memory dysfunction in mice. Background The brainegut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established. Objective To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation. Methods Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated. Results No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota. Conclusions The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.. irritable-bowel-syndrome| citrobacter-rodentium infection| murine colonic hyperplasia| chronic psychological stress| intestinal barrier function| maternal separation| escherichia-coli| synaptic plasticity| spatial memory| c-fos.	MAR-2011	irritable-bowel-syndrome| citrobacter-rodentium infection| murine colonic hyperplasia| chronic psychological stress| intestinal barrier function| maternal separation| escherichia-coli| synaptic plasticity| spatial memory| c-fos	Gareau, MG; Wine, E; Rodrigues, DM; Cho, JH; Whary, MT; Philpott, DJ; MacQueen, G; Sherman, PM	Bacterial infection causes stress-induced memory dysfunction in mice		GUT		IRRITABLE-BOWEL-SYNDROME; CITROBACTER-RODENTIUM INFECTION; MURINE COLONIC HYPERPLASIA; CHRONIC PSYCHOLOGICAL STRESS; INTESTINAL BARRIER FUNCTION; MATERNAL SEPARATION; ESCHERICHIA-COLI; SYNAPTIC PLASTICITY; SPATIAL MEMORY; C-FOS	Background The brainegut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established. Objective To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation. Methods Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated. Results No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota. Conclusions The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.	68	159	2011	11	10.1136/gut.2009.202515	Gastroenterology & Hepatology
"The burden of disease associated with filaggrin mutations: A population-based, longitudinal birth cohort study. Background: Atopic disease is a major health problem. Mutations in the filaggrin gene (FLG) confer major susceptibility to eczema and related asthma. Objective: We sought to determine the natural history and burden of atopic disease conferred by the 2 most common FLG mutations in a large, population-based birth cohort study. Methods: We analyzed the effect of the most common null alleles (R501X and 2282del4) on several atopic phenotypes in a cohort of approximately 7000 English children born in 1990-1991. Results: FLG null alleles associated strongly with eczema; eczema associated with these mutations presents in early life and is more persistent (hazard ratio for eczema resolution for those with FLG mutations to FLG wild type, 0.67; 95% CI, 0.58-0.77; P = 5 x 10(-8)). FLG mutations conferred a population asthma risk of 1.80 (95% CI, 1.34-2.41; P = .00019); asthma risk was especially high in the context of eczema (odds ratio, 3.16; 95% CI, 2.25-4.43; P = 1.4 x 10(-11)). Strong associations were identified with sensitization to grass, house dust mite, and cat dander and sensitization to multiple allergens (odds ratio, 2.12; 95% CI, 1.03-4.37; P = 5.42 x 10(-27)). Conclusion: FLG mutations are strong genetic determinants of eczema, early wheeze, asthma in the context of eczema, and atopic sensitization. They confer risk of a particular trajectory for eczema, with increased duration of disease and greater risk of asthma and multiple allergic sensitizations. FLG alleles help define the risk profile of children with eczema and help define the ""eczema plus early wheeze"" and ""eczema plus asthma"" phenotypes.. eczema| atopic dermatitis| asthma| skin barrier| filaggrin| birth cohort| atopy|atopic-dermatitis| bronchial responsiveness| barrier| methodology| phenotypes| children| alspac| asthma| eczema| gene."	APR-2008	eczema| atopic dermatitis| asthma| skin barrier| filaggrin| birth cohort| atopy|atopic-dermatitis| bronchial responsiveness| barrier| methodology| phenotypes| children| alspac| asthma| eczema| gene	Henderson, J; Northstone, K; Lee, SP; Liao, HH; Zhao, YW; Pembrey, M; Mukhopadhyay, S; Smith, GD; Palmer, CNA; McLean, WHI; Irvine, AD	The burden of disease associated with filaggrin mutations: A population-based, longitudinal birth cohort study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	eczema; atopic dermatitis; asthma; skin barrier; filaggrin; birth cohort; atopy	ATOPIC-DERMATITIS; BRONCHIAL RESPONSIVENESS; BARRIER; METHODOLOGY; PHENOTYPES; CHILDREN; ALSPAC; ASTHMA; ECZEMA; GENE	"Background: Atopic disease is a major health problem. Mutations in the filaggrin gene (FLG) confer major susceptibility to eczema and related asthma. Objective: We sought to determine the natural history and burden of atopic disease conferred by the 2 most common FLG mutations in a large, population-based birth cohort study. Methods: We analyzed the effect of the most common null alleles (R501X and 2282del4) on several atopic phenotypes in a cohort of approximately 7000 English children born in 1990-1991. Results: FLG null alleles associated strongly with eczema; eczema associated with these mutations presents in early life and is more persistent (hazard ratio for eczema resolution for those with FLG mutations to FLG wild type, 0.67; 95% CI, 0.58-0.77; P = 5 x 10(-8)). FLG mutations conferred a population asthma risk of 1.80 (95% CI, 1.34-2.41; P = .00019); asthma risk was especially high in the context of eczema (odds ratio, 3.16; 95% CI, 2.25-4.43; P = 1.4 x 10(-11)). Strong associations were identified with sensitization to grass, house dust mite, and cat dander and sensitization to multiple allergens (odds ratio, 2.12; 95% CI, 1.03-4.37; P = 5.42 x 10(-27)). Conclusion: FLG mutations are strong genetic determinants of eczema, early wheeze, asthma in the context of eczema, and atopic sensitization. They confer risk of a particular trajectory for eczema, with increased duration of disease and greater risk of asthma and multiple allergic sensitizations. FLG alleles help define the risk profile of children with eczema and help define the ""eczema plus early wheeze"" and ""eczema plus asthma"" phenotypes."	20	159	2008	6	10.1016/j.jaci.2008.01.026	Allergy; Immunology
Mechanisms of disease: the hygiene hypothesis revisited. In industrialized countries the incidence of diseases caused by immune dysregulation has risen. Epidemiologic studies initially suggested this was connected to a reduction in the incidence of infectious diseases; however, an association with defects in immunoregulation is now being recognized. Effector T(H)1 and T(H)2 cells are controlled by specialized subsets of regulatory T cells. Some pathogens can induce regulatory cells to evade immune elimination, but regulatory pathways are homeostatic and mainly triggered by harmless microorganisms. Helminths, saprophytic mycobacteria, bifidobacteria and lactobacilli, which induce immunoregulatory mechanisms in the host, ameliorate aberrant immune responses in the setting of allergy and inflammatory bowel disease. These organisms cause little, if any, harm, and have been part of human microecology for millennia; however, they are now less frequent or even absent in the human environment of westernized societies. Deficient exposure to these 'old friends' might explain the increase in immunodysregulatory disorders. The use of probiotics, prebiotics, helminths or microbe-derived immunoregulatory vaccines might, therefore, become a valuable approach to disease prevention.. microbiota| probiotics| prebiotics| regulatory t cells| tolerance|regulatory t-cells| inflammatory-bowel-disease| active ulcerative-colitis| placebo-controlled trial| trichuris-suis therapy| bordetella-pertussis| multiple-sclerosis| crohns-disease| transcriptional regulation| intestinal microflora.	MAY-2006	microbiota| probiotics| prebiotics| regulatory t cells| tolerance|regulatory t-cells| inflammatory-bowel-disease| active ulcerative-colitis| placebo-controlled trial| trichuris-suis therapy| bordetella-pertussis| multiple-sclerosis| crohns-disease| transcriptional regulation| intestinal microflora	Guarner, F; Bourdet-Sicard, R; Brandtzaeg, P; Gill, HS; McGuirk, P; van Eden, W; Versalovic, J; Weinstock, JV; Rook, GAW	Mechanisms of disease: the hygiene hypothesis revisited		NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY	microbiota; probiotics; prebiotics; regulatory T cells; tolerance	REGULATORY T-CELLS; INFLAMMATORY-BOWEL-DISEASE; ACTIVE ULCERATIVE-COLITIS; PLACEBO-CONTROLLED TRIAL; TRICHURIS-SUIS THERAPY; BORDETELLA-PERTUSSIS; MULTIPLE-SCLEROSIS; CROHNS-DISEASE; TRANSCRIPTIONAL REGULATION; INTESTINAL MICROFLORA	In industrialized countries the incidence of diseases caused by immune dysregulation has risen. Epidemiologic studies initially suggested this was connected to a reduction in the incidence of infectious diseases; however, an association with defects in immunoregulation is now being recognized. Effector T(H)1 and T(H)2 cells are controlled by specialized subsets of regulatory T cells. Some pathogens can induce regulatory cells to evade immune elimination, but regulatory pathways are homeostatic and mainly triggered by harmless microorganisms. Helminths, saprophytic mycobacteria, bifidobacteria and lactobacilli, which induce immunoregulatory mechanisms in the host, ameliorate aberrant immune responses in the setting of allergy and inflammatory bowel disease. These organisms cause little, if any, harm, and have been part of human microecology for millennia; however, they are now less frequent or even absent in the human environment of westernized societies. Deficient exposure to these 'old friends' might explain the increase in immunodysregulatory disorders. The use of probiotics, prebiotics, helminths or microbe-derived immunoregulatory vaccines might, therefore, become a valuable approach to disease prevention.	82	159	2006	10	10.1038/ncpgasthep0471	Gastroenterology & Hepatology
"Severe asthma in adults. Severe asthma remains poorly understood and frustrating to care for, partly because it is a heterogeneous disease. Patients with severe asthma disproportionately consume health care resources related to asthma. Severe asthma may develop over time, or shortly after onset of the disease. The genetic and environmental elements that may be most important in the development of severe disease are poorly understood, but likely include both allergic and nonallergic elements. Physiologically, these patients often have air trapping, airway collapsibility, and a high degree of methacholine hyper-responsiveness. Specific phenotypes of severe asthma are only beginning to be defined. However, describing severe asthma by age at onset (early- vs. late-onset) appears to describe two phenotypes that differ at immunologic, physiologic, epidemiologic, and pathologic levels. In particular, early-onset severe asthma is a more allergic-associated disease than late-onset severe asthma. In addition, patients with severe asthma can be defined on the basis of presence and type of inflammation. Severe asthma with persistent eosinophilia (of either early or late onset) is more symptomatic and has more near-fatal events. However, at least 50% of patients with severe asthma have very little identifiable inflammation. Thus, ""steroid resistance"" may occur at numerous levels, not all of which are caused by a lack of effect of steroids on inflammation. Treatment remains problematic, with corticosteroids remaining the most effective therapy. However, 5-lipoxygenase inhibitors, anti-IgE, and immunomodulatory drugs are also likely to have a place in treatment. Improving therapy in this disease will require a better understanding of the phenotypes involved.. asthma| inflammation| physiology| phenotypes| remodeling| treatment|near-fatal asthma| steroid-resistant asthma| life-threatening asthma| air-flow obstruction| glucocorticoid-receptor| persistent asthma| lung-function| clinical characteristics| childhood asthma| bronchial-asthma."	JUL 15-2005	asthma| inflammation| physiology| phenotypes| remodeling| treatment|near-fatal asthma| steroid-resistant asthma| life-threatening asthma| air-flow obstruction| glucocorticoid-receptor| persistent asthma| lung-function| clinical characteristics| childhood asthma| bronchial-asthma	Wenzel, S	Severe asthma in adults		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; inflammation; physiology; phenotypes; remodeling; treatment	NEAR-FATAL ASTHMA; STEROID-RESISTANT ASTHMA; LIFE-THREATENING ASTHMA; AIR-FLOW OBSTRUCTION; GLUCOCORTICOID-RECEPTOR; PERSISTENT ASTHMA; LUNG-FUNCTION; CLINICAL CHARACTERISTICS; CHILDHOOD ASTHMA; BRONCHIAL-ASTHMA	"Severe asthma remains poorly understood and frustrating to care for, partly because it is a heterogeneous disease. Patients with severe asthma disproportionately consume health care resources related to asthma. Severe asthma may develop over time, or shortly after onset of the disease. The genetic and environmental elements that may be most important in the development of severe disease are poorly understood, but likely include both allergic and nonallergic elements. Physiologically, these patients often have air trapping, airway collapsibility, and a high degree of methacholine hyper-responsiveness. Specific phenotypes of severe asthma are only beginning to be defined. However, describing severe asthma by age at onset (early- vs. late-onset) appears to describe two phenotypes that differ at immunologic, physiologic, epidemiologic, and pathologic levels. In particular, early-onset severe asthma is a more allergic-associated disease than late-onset severe asthma. In addition, patients with severe asthma can be defined on the basis of presence and type of inflammation. Severe asthma with persistent eosinophilia (of either early or late onset) is more symptomatic and has more near-fatal events. However, at least 50% of patients with severe asthma have very little identifiable inflammation. Thus, ""steroid resistance"" may occur at numerous levels, not all of which are caused by a lack of effect of steroids on inflammation. Treatment remains problematic, with corticosteroids remaining the most effective therapy. However, 5-lipoxygenase inhibitors, anti-IgE, and immunomodulatory drugs are also likely to have a place in treatment. Improving therapy in this disease will require a better understanding of the phenotypes involved."	120	159	2005	12	10.1164/rccm.200409-1181PP	General & Internal Medicine; Respiratory System
Ultrafine particle deposition in subjects with asthma. Ambient air particles in the ultrafine size range (diameter < 100 nm) may contribute to the health effects of particulate matter. However, there are few data on ultrafine particle deposition during spontaneous breathing, and none in people with asthma. Sixteen subjects with mild to moderate asthma were exposed for 2 hr, by mouthpiece, to ultrafine carbon particles with a count median diameter (CMD) of 23 nm and a geometric standard deviation of 1.6. Deposition was measured during spontaneous breathing at rest (minute ventilation, 13.3 +/- 2.0 L/min) and exercise (minute ventilation, 41.9 +/- 9.0 L/min). The mean SD fractional deposition was 0.76 +/- 0.05 by particle number and 0.69 +/- 0.07 by particle mass concentration. The number deposition fraction increased as particle size decreased, reaching 0.84 +/- 0.03 for the smallest particles (midpoint CMD = 8.7 nm). No differences between sexes were observed. The deposition fraction increased during exercise to 0.86 +/- 0.04 and 0.79 +/- 0.05 by particle number and mass concentration, respectively, and reached 0.93 +/- 0.02 for the smallest particles. Experimental deposition data exceeded model predictions during exercise. The deposition at rest was greater in these subjects with asthma than in previously studied healthy subjects (0.76 +/- 0.05 vs. 0.65 +/- 0.10, p < 0.001). The efficient respiratory deposition of ultrafine particles increases further in subjects with asthma.. air pollution| asthma| deposition| dosimetry| inhalation| ultrafine particles|particulate air-pollution| breathing patterns| respiratory-tract| lung deposition| fine particles| disease| healthy| mortality| exposure| number.	JUN-2004	air pollution| asthma| deposition| dosimetry| inhalation| ultrafine particles|particulate air-pollution| breathing patterns| respiratory-tract| lung deposition| fine particles| disease| healthy| mortality| exposure| number	Chalupa, DC; Morrow, PE; Oberdorster, G; Utell, MJ; Frampton, MW	Ultrafine particle deposition in subjects with asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma; deposition; dosimetry; inhalation; ultrafine particles	PARTICULATE AIR-POLLUTION; BREATHING PATTERNS; RESPIRATORY-TRACT; LUNG DEPOSITION; FINE PARTICLES; DISEASE; HEALTHY; MORTALITY; EXPOSURE; NUMBER	Ambient air particles in the ultrafine size range (diameter < 100 nm) may contribute to the health effects of particulate matter. However, there are few data on ultrafine particle deposition during spontaneous breathing, and none in people with asthma. Sixteen subjects with mild to moderate asthma were exposed for 2 hr, by mouthpiece, to ultrafine carbon particles with a count median diameter (CMD) of 23 nm and a geometric standard deviation of 1.6. Deposition was measured during spontaneous breathing at rest (minute ventilation, 13.3 +/- 2.0 L/min) and exercise (minute ventilation, 41.9 +/- 9.0 L/min). The mean SD fractional deposition was 0.76 +/- 0.05 by particle number and 0.69 +/- 0.07 by particle mass concentration. The number deposition fraction increased as particle size decreased, reaching 0.84 +/- 0.03 for the smallest particles (midpoint CMD = 8.7 nm). No differences between sexes were observed. The deposition fraction increased during exercise to 0.86 +/- 0.04 and 0.79 +/- 0.05 by particle number and mass concentration, respectively, and reached 0.93 +/- 0.02 for the smallest particles. Experimental deposition data exceeded model predictions during exercise. The deposition at rest was greater in these subjects with asthma than in previously studied healthy subjects (0.76 +/- 0.05 vs. 0.65 +/- 0.10, p < 0.001). The efficient respiratory deposition of ultrafine particles increases further in subjects with asthma.	29	159	2004	4	10.1289/ehp.6851	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
The anti-allergic effects of lactic acid bacteria are strain dependent and mediated by effects on both Th1/Th2 cytokine expression and balance. Background: There is growing interest in the immune-stimulating effect and in particular, the anti-allergic effect, of lactic acid bacteria (LAB). However, no comprehensive studies have been done that compare the immune-stimulating potential of LAB strains. Methods: The in vitro immune-stimulating effects on Th1/Th2 balance of more than 100 LAB strains were compared in splenocytes from ovalbumin-sensitized Th2-polarized mice. The in vivo anti-allergic ability of strain KW3110 was studied in the Th2-polarized model by detecting serum IgE concentration, Th1/Th2 cytokine secretion from splenocytes, and the expression of co-stimulatory molecules on macrophages. Results: In vitro studies from Th2-polarized splenocytes, using IL-12 as a Th1 parameter and IL-4 secretion as a Th2 parameter revealed a wide variety of IL-12- inducing and IL-4-repressing activities, depending on the strain of LAB, not depending on the species. However, evaluation of individual strains in vivo revealed that after exposure to Lactobacillus paracasei KW3110 strain, the serum IgE elevation elicited by repeated OVA injection of mice was strongly inhibited. Cytokine secretion from splenocytes 20 weeks after KW3110 administration showed increased IL-12 and decreased IL-4 expression. Both CD40 and B7-1 expression on macrophages was upregulated by administration of KW3110. Conclusions: Improving the consequences of the Th1/Th2 imbalance by administration of LAB was dependent upon the LAB strain rather than the LAB species. Oral KW3110 administration in the mouse allergy model directed the Th1/Th2 balance toward Th1 through the maturation of APCs and inhibition of serum IgE elevation. Copyright (C) 2004 S. Karger AG, Basel.. lactic acid bacteria| ige| th1| th2| lactobacillus paracasei strain kw3110|lipoteichoic acid| dendritic cells| interferon-gamma| staphylococcus-aureus| ifn-gamma| interleukin-12| activation| induction| receptor| il-12.	2004	lactic acid bacteria| ige| th1| th2| lactobacillus paracasei strain kw3110|lipoteichoic acid| dendritic cells| interferon-gamma| staphylococcus-aureus| ifn-gamma| interleukin-12| activation| induction| receptor| il-12	Fujiwara, D; Inoue, S; Wakabayashi, H; Fujii, T	The anti-allergic effects of lactic acid bacteria are strain dependent and mediated by effects on both Th1/Th2 cytokine expression and balance		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	lactic acid bacteria; IgE; Th1; Th2; Lactobacillus paracasei strain KW3110	LIPOTEICHOIC ACID; DENDRITIC CELLS; INTERFERON-GAMMA; STAPHYLOCOCCUS-AUREUS; IFN-GAMMA; INTERLEUKIN-12; ACTIVATION; INDUCTION; RECEPTOR; IL-12	Background: There is growing interest in the immune-stimulating effect and in particular, the anti-allergic effect, of lactic acid bacteria (LAB). However, no comprehensive studies have been done that compare the immune-stimulating potential of LAB strains. Methods: The in vitro immune-stimulating effects on Th1/Th2 balance of more than 100 LAB strains were compared in splenocytes from ovalbumin-sensitized Th2-polarized mice. The in vivo anti-allergic ability of strain KW3110 was studied in the Th2-polarized model by detecting serum IgE concentration, Th1/Th2 cytokine secretion from splenocytes, and the expression of co-stimulatory molecules on macrophages. Results: In vitro studies from Th2-polarized splenocytes, using IL-12 as a Th1 parameter and IL-4 secretion as a Th2 parameter revealed a wide variety of IL-12- inducing and IL-4-repressing activities, depending on the strain of LAB, not depending on the species. However, evaluation of individual strains in vivo revealed that after exposure to Lactobacillus paracasei KW3110 strain, the serum IgE elevation elicited by repeated OVA injection of mice was strongly inhibited. Cytokine secretion from splenocytes 20 weeks after KW3110 administration showed increased IL-12 and decreased IL-4 expression. Both CD40 and B7-1 expression on macrophages was upregulated by administration of KW3110. Conclusions: Improving the consequences of the Th1/Th2 imbalance by administration of LAB was dependent upon the LAB strain rather than the LAB species. Oral KW3110 administration in the mouse allergy model directed the Th1/Th2 balance toward Th1 through the maturation of APCs and inhibition of serum IgE elevation. Copyright (C) 2004 S. Karger AG, Basel.	31	159	2004	11	10.1159/000081305	Allergy; Immunology
Relation of distribution- and anchor-based approaches in interpretation of changes in health-related quality of life. Background. Approaches to interpretation of quality of life changes in clinical trials have fallen into two camps: those that rely on the distribution of changes and the Effect Size (ES), and those that use some external anchor, such as patient judgments of change, which is then used to compute a Minimally Important Difference (MID), the proportion benefiting from treatment, p(B), and the Number Needed to Treat (NNT). OBJECTIVE. To examine the relationship between the ES and p(B), and the impact of the MID on this relationship. METHODS. Simulation was used based on a normal distribution to compute the proportion of patients benefiting in both parallel group and crossover designs, for various values of the ES and the MID. The agreement of the simulation with empirical data from four studies of asthma and respiratory disease was assessed. The effect of skewness in the distributions of change scores on the relationship between ES and p(B) was also examined. RESULTS. The simulation showed a near-linear relationship between ES and p(B), which was nearly independent of the value of the MID. Agreement of the simulation with the empirical data were excellent. Although the curves differed for crossover and parallel group designs, the general form was similar. Introducing moderate skew into the distributions had minimal impact on the relationship. CONCLUSIONS. The proportion of patients who will benefit from treatment can be directly estimated from the ES, and is nearly independent of the choice of MID. Effect size and anchor based approaches provide equivalent information in this situation.. effect size| nnt (number needed to treat)|obstructive pulmonary-disease| of-life| important difference| rheumatoid-arthritis| clinical-trials| rehabilitation| questionnaire| asthma| home.	OCT-2001	effect size| nnt (number needed to treat)|obstructive pulmonary-disease| of-life| important difference| rheumatoid-arthritis| clinical-trials| rehabilitation| questionnaire| asthma| home	Norman, GR; Sridar, FG; Guyatt, GH; Walter, SD	Relation of distribution- and anchor-based approaches in interpretation of changes in health-related quality of life		MEDICAL CARE	effect size; NNT (number needed to treat)	OBSTRUCTIVE PULMONARY-DISEASE; OF-LIFE; IMPORTANT DIFFERENCE; RHEUMATOID-ARTHRITIS; CLINICAL-TRIALS; REHABILITATION; QUESTIONNAIRE; ASTHMA; HOME	Background. Approaches to interpretation of quality of life changes in clinical trials have fallen into two camps: those that rely on the distribution of changes and the Effect Size (ES), and those that use some external anchor, such as patient judgments of change, which is then used to compute a Minimally Important Difference (MID), the proportion benefiting from treatment, p(B), and the Number Needed to Treat (NNT). OBJECTIVE. To examine the relationship between the ES and p(B), and the impact of the MID on this relationship. METHODS. Simulation was used based on a normal distribution to compute the proportion of patients benefiting in both parallel group and crossover designs, for various values of the ES and the MID. The agreement of the simulation with empirical data from four studies of asthma and respiratory disease was assessed. The effect of skewness in the distributions of change scores on the relationship between ES and p(B) was also examined. RESULTS. The simulation showed a near-linear relationship between ES and p(B), which was nearly independent of the value of the MID. Agreement of the simulation with the empirical data were excellent. Although the curves differed for crossover and parallel group designs, the general form was similar. Introducing moderate skew into the distributions had minimal impact on the relationship. CONCLUSIONS. The proportion of patients who will benefit from treatment can be directly estimated from the ES, and is nearly independent of the choice of MID. Effect size and anchor based approaches provide equivalent information in this situation.	21	159	2001	9	10.1097/00005650-200110000-00002	Health Care Sciences & Services; Public, Environmental & Occupational Health
Onset and remission of allergic rhinitis and asthma and the relationship with atopic sensitization and smoking. The aim of this study was to assess the influence of some risk factors for onset and remission of allergic rhinitis and asthma in Swedish adults. A random sample of 1,370 subjects, age 20 to 44 yr was investigated by means of postal questionnaires in 1990 and 1993. Skin prick tests were conducted in 1991-1992. The association between risk factors and onset or remission of allergic rhinitis and asthma was estimated using multivariate logistic regression analysis. Onset of allergic rhinitis was associated with sensitization to birch (odds ratio [OR] = 6.5), Parietaria (OR = 7.4); and pets (OR = 3.0) and with female sex (OR = 1.9). Onset of asthma was associated with allergic rhinitis (OR = 4.9), sensitization to pets (OR = 2.4); and with smoking (OR = 3.0). Onset of asthma was strongly associated with allergic rhinitis among atopics (OR = 5.7), but onset of asthma and rhinitis also tended to be related among nonatopics (OR = 3.5). A strong association between smoking and onset of asthma was found among nonatopics (OR = 5.7). In conclusion, sensitization to pollens and pets were risk factors for onset of allergic rhinitis, whereas allergic rhinitis, sensitization to pets, and smoking were risk factors for onset of asthma.. swedish schoolchildren| chronic-bronchitis| cat| symptoms| ige| sweden| adults| areas| homes| pets.	SEP-2000	swedish schoolchildren| chronic-bronchitis| cat| symptoms| ige| sweden| adults| areas| homes| pets	Plaschke, PP; Janson, C; Norrman, E; Bjornsson, E; Ellbjar, S; Jarvholm, B	Onset and remission of allergic rhinitis and asthma and the relationship with atopic sensitization and smoking		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		SWEDISH SCHOOLCHILDREN; CHRONIC-BRONCHITIS; CAT; SYMPTOMS; IGE; SWEDEN; ADULTS; AREAS; HOMES; PETS	The aim of this study was to assess the influence of some risk factors for onset and remission of allergic rhinitis and asthma in Swedish adults. A random sample of 1,370 subjects, age 20 to 44 yr was investigated by means of postal questionnaires in 1990 and 1993. Skin prick tests were conducted in 1991-1992. The association between risk factors and onset or remission of allergic rhinitis and asthma was estimated using multivariate logistic regression analysis. Onset of allergic rhinitis was associated with sensitization to birch (odds ratio [OR] = 6.5), Parietaria (OR = 7.4); and pets (OR = 3.0) and with female sex (OR = 1.9). Onset of asthma was associated with allergic rhinitis (OR = 4.9), sensitization to pets (OR = 2.4); and with smoking (OR = 3.0). Onset of asthma was strongly associated with allergic rhinitis among atopics (OR = 5.7), but onset of asthma and rhinitis also tended to be related among nonatopics (OR = 3.5). A strong association between smoking and onset of asthma was found among nonatopics (OR = 5.7). In conclusion, sensitization to pollens and pets were risk factors for onset of allergic rhinitis, whereas allergic rhinitis, sensitization to pets, and smoking were risk factors for onset of asthma.	32	159	2000	5		General & Internal Medicine; Respiratory System
Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. Atopic asthma is a chronic disease of the airways that has taken on epidemic proportions in the industrialized world. The increase in asthma rates has been linked epidemiologically to the rapid disappearance of Helicobacter pylori, a bacterial pathogen that persistently colonizes the human stomach, from Western societies. In this study, we have utilized mouse models of allergic airway disease induced by ovalbumin or house dust mite allergen to experimentally examine a possible inverse correlation between H. pylori and asthma. H. pylori infection efficiently protected mice from airway hyperresponsiveness, tissue inflammation, and goblet cell metaplasia, which are hallmarks of asthma, and prevented allergen-induced pulmonary and bronchoalveolar infiltration with eosinophils, Th2 cells, and Th17 cells. Protection against asthma was most robust in mice infected neonatally and was abrogated by antibiotic eradication of H. pylori. Asthma protection was further associated with impaired maturation of lung-infiltrating dendritic cells and the accumulation of highly suppressive Tregs in the lungs. Systemic Treg depletion abolished asthma protection; conversely, the adoptive transfer of purified Treg populations was sufficient to transfer protection from infected donor mice to uninfected recipients. Our results thus provide experimental evidence for a beneficial effect of H. pylori colonization on the development of allergen-induced asthma.. airway inflammation| protect| mice.	AUG-2011	airway inflammation| protect| mice	Arnold, IC; Dehzad, N; Reuter, S; Martin, H; Becher, B; Taube, C; Muller, A	Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells		JOURNAL OF CLINICAL INVESTIGATION		AIRWAY INFLAMMATION; PROTECT; MICE	Atopic asthma is a chronic disease of the airways that has taken on epidemic proportions in the industrialized world. The increase in asthma rates has been linked epidemiologically to the rapid disappearance of Helicobacter pylori, a bacterial pathogen that persistently colonizes the human stomach, from Western societies. In this study, we have utilized mouse models of allergic airway disease induced by ovalbumin or house dust mite allergen to experimentally examine a possible inverse correlation between H. pylori and asthma. H. pylori infection efficiently protected mice from airway hyperresponsiveness, tissue inflammation, and goblet cell metaplasia, which are hallmarks of asthma, and prevented allergen-induced pulmonary and bronchoalveolar infiltration with eosinophils, Th2 cells, and Th17 cells. Protection against asthma was most robust in mice infected neonatally and was abrogated by antibiotic eradication of H. pylori. Asthma protection was further associated with impaired maturation of lung-infiltrating dendritic cells and the accumulation of highly suppressive Tregs in the lungs. Systemic Treg depletion abolished asthma protection; conversely, the adoptive transfer of purified Treg populations was sufficient to transfer protection from infected donor mice to uninfected recipients. Our results thus provide experimental evidence for a beneficial effect of H. pylori colonization on the development of allergen-induced asthma.	19	158	2011	6	10.1172/JCI45041	Research & Experimental Medicine
Climate and the prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in children. Aims: To investigate the association between climate and atopic diseases using worldwide data from 146 centres of the International Study of Asthma and Allergies in Childhood (ISAAC). Methods: Between 1992 and 1996, each centre studied random samples of children aged 13 - 14 and 6 - 7 years (approx. 3000 per age group and centre) using standardised written and video questionnaires on symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema during the past 12 months. Data on long term climatic conditions in the centres were abstracted from one standardised source, and mixed linear regression models calculated to take the clustering of centres within countries into account. Results: In Western Europe ( 57 centres in 12 countries), the prevalence of asthma symptoms, assessed by written questionnaire, increased by 2.7% ( 95% CI 1.0% to 4.5%) with an increase in the estimated annual mean of indoor relative humidity of 10%. Similar associations were seen for the video questionnaire and the younger age group. Altitude and the annual variation of temperature and relative humidity outdoors were negatively associated with asthma symptoms. The prevalence of eczema symptoms correlated with latitude ( positively) and mean annual outdoor temperature ( negatively). Conclusions: Results suggest that climate may affect the prevalence of asthma and atopic eczema in children.. house-dust mites| childhood isaac| worldwide variations| respiratory health| exposure| sensitization| areas| home| rhinoconjunctivitis| adolescents.	JUL-2004	house-dust mites| childhood isaac| worldwide variations| respiratory health| exposure| sensitization| areas| home| rhinoconjunctivitis| adolescents	Weiland, SK; Husing, A; Strachan, DP; Rzehak, P; Pearce, N	Climate and the prevalence of symptoms of asthma, allergic rhinitis, and atopic eczema in children		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		HOUSE-DUST MITES; CHILDHOOD ISAAC; WORLDWIDE VARIATIONS; RESPIRATORY HEALTH; EXPOSURE; SENSITIZATION; AREAS; HOME; RHINOCONJUNCTIVITIS; ADOLESCENTS	Aims: To investigate the association between climate and atopic diseases using worldwide data from 146 centres of the International Study of Asthma and Allergies in Childhood (ISAAC). Methods: Between 1992 and 1996, each centre studied random samples of children aged 13 - 14 and 6 - 7 years (approx. 3000 per age group and centre) using standardised written and video questionnaires on symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema during the past 12 months. Data on long term climatic conditions in the centres were abstracted from one standardised source, and mixed linear regression models calculated to take the clustering of centres within countries into account. Results: In Western Europe ( 57 centres in 12 countries), the prevalence of asthma symptoms, assessed by written questionnaire, increased by 2.7% ( 95% CI 1.0% to 4.5%) with an increase in the estimated annual mean of indoor relative humidity of 10%. Similar associations were seen for the video questionnaire and the younger age group. Altitude and the annual variation of temperature and relative humidity outdoors were negatively associated with asthma symptoms. The prevalence of eczema symptoms correlated with latitude ( positively) and mean annual outdoor temperature ( negatively). Conclusions: Results suggest that climate may affect the prevalence of asthma and atopic eczema in children.	45	158	2004	7	10.1136/oem.2002.006809	Public, Environmental & Occupational Health
Chronic sinusitis in severe asthma is related to sputum eosinophilia. Background: Chronic rhinosinusitis and asthma are conditions that frequently coexist, particularly in severe asthma. The precise mechanism of the relationship between upper and lower airway, inflammation is still a matter of debate. We hypothesized that the extent of inflammation in the nasal mucosa is related to lung function and inflammation in the bronchial mucosa in patients with severe asthma. Objective: We sought to investigate the relationship between sinonasal inflammation as assessed on computed tomography (CT) scanning, lung function, sputum eosinophilia, and nitric oxide (NO) in exhaled air in patients with severe asthma. Methods: Eighty-nine nonsmoking outpatients with severe asthma (29 men and 60 women; mean age 45 years; age range, 18-74 years) were included in this study. CT scans were scored (0-30) by a blinded investigator using a validated method. Lung function, NO in exhaled air, and sputum eosinophils were measured by using standard procedures. Results: CT scans showed abnormalities in 84% of patients. Extensive sinus disease (score 12-30) was found in 24% of patients. There was a significant positive correlation between CT scores and eosinophils in peripheral blood (R-s = 0.46) and induced sputum (R-s = 0.40) and level of exhaled NO (R-s = 0.45, P < .01). CT scores were also positively related to functional residual capacity and inversely, related to diffusion capacity, particularly in patients with adult-onset asthma (R-s = 0.47 and R-s = -0.53, respectively). Conclusions: The results of this study show a direct relationship between sinonasal mucosa thickness and bronchial inflammation in severe asthma, particularly in patients with adult-onset disease. Whether sinus disease directly affects the intensity of bronchial inflammation is still an unanswered question.. asthma| severity-of-illness index| age of onset| inflammation| nasal mucosa| eosinophils| sputum| computed tomography| human|nasal| inflammation| rhinitis| airways.	APR-2002	asthma| severity-of-illness index| age of onset| inflammation| nasal mucosa| eosinophils| sputum| computed tomography| human|nasal| inflammation| rhinitis| airways	ten Brinke, A; Grootendorst, DC; Schmidt, JT; de Bruine, FT; van Buchem, MA; Sterk, PJ; Rabe, KF; Bel, EH	Chronic sinusitis in severe asthma is related to sputum eosinophilia		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; severity-of-illness index; age of onset; inflammation; nasal mucosa; eosinophils; sputum; computed tomography; human	NASAL; INFLAMMATION; RHINITIS; AIRWAYS	Background: Chronic rhinosinusitis and asthma are conditions that frequently coexist, particularly in severe asthma. The precise mechanism of the relationship between upper and lower airway, inflammation is still a matter of debate. We hypothesized that the extent of inflammation in the nasal mucosa is related to lung function and inflammation in the bronchial mucosa in patients with severe asthma. Objective: We sought to investigate the relationship between sinonasal inflammation as assessed on computed tomography (CT) scanning, lung function, sputum eosinophilia, and nitric oxide (NO) in exhaled air in patients with severe asthma. Methods: Eighty-nine nonsmoking outpatients with severe asthma (29 men and 60 women; mean age 45 years; age range, 18-74 years) were included in this study. CT scans were scored (0-30) by a blinded investigator using a validated method. Lung function, NO in exhaled air, and sputum eosinophils were measured by using standard procedures. Results: CT scans showed abnormalities in 84% of patients. Extensive sinus disease (score 12-30) was found in 24% of patients. There was a significant positive correlation between CT scores and eosinophils in peripheral blood (R-s = 0.46) and induced sputum (R-s = 0.40) and level of exhaled NO (R-s = 0.45, P < .01). CT scores were also positively related to functional residual capacity and inversely, related to diffusion capacity, particularly in patients with adult-onset asthma (R-s = 0.47 and R-s = -0.53, respectively). Conclusions: The results of this study show a direct relationship between sinonasal mucosa thickness and bronchial inflammation in severe asthma, particularly in patients with adult-onset disease. Whether sinus disease directly affects the intensity of bronchial inflammation is still an unanswered question.	33	158	2002	6	10.1067/mai.2002.122458	Allergy; Immunology
Human alveolar macrophage responses to air pollution particulates are associated with insoluble components of coarse material, including particulate endotoxin. Inhalation of particulate matter in the ambient air has been shown to cause pulmonary morbidity and exacerbate asthma. Alveolar macrophage (AIM) are essential for effective removal of inhaled particles and microbes in the lower airways. While some particles minimally effect AM function others inhibit antimicrobial activity or cause cytokine and growth factor production leading to inflammation and tissue remodeling. This study has investigated the effects of water soluble (s) and insoluble (is) components of Chapel Hill, North Carolina ambient particulate matter in the size ranges 0.1-2.5 Ccm (PM2.5) and 2.5-10 mum (PM10) diameter, on human AM IL-6, TNF alpha, and MCP-1 cytokine production and host defense mechanisms including phagocytosis and oxidant production. Cytokines were found to be induced by isPM10 to a much higher extent (>50-fold) than sPM10, which in turn stimulated production better than isPM2.5, while sPM2.5 was inactive. Previous studies have indicated that endotoxin (ETOX) is a component of sPM10 responsible for cytokine production. Here, it is shown that inhibition of isPM10-induced cytokine production was partially achieved with polymyxin B and LPS-binding protein (LBP), but not with a metal chelator, implicating ETOX as a cytokine-inducing moiety also in isPM10. In addition to inducing cytokines, exposure to isPM10, but not the other PM fractions, also inhibited phagocytosis and oxidant generation in response to yeast. This inhibition was ETOX independent. The decrease in host defenses may be the result of apoptosis in the AM population, which was also found to be specifically caused by isPM10. These results show that the functional capacity of AM is selectively modulated by insoluble components of coarse PM, including the biocontaminant ETOX.. human macrophage| endotoxin| air pollution pm10 and pm2.5| phagocytosis| apoptosis| cytokines|necrosis-factor-alpha| fine particles| hospital admissions| respiratory health| oxidative burst| blood monocytes| children| asthma| lipopolysaccharide| phagocytosis.	FEB 15-2001	human macrophage| endotoxin| air pollution pm10 and pm2.5| phagocytosis| apoptosis| cytokines|necrosis-factor-alpha| fine particles| hospital admissions| respiratory health| oxidative burst| blood monocytes| children| asthma| lipopolysaccharide| phagocytosis	Soukup, JM; Becker, S	Human alveolar macrophage responses to air pollution particulates are associated with insoluble components of coarse material, including particulate endotoxin		TOXICOLOGY AND APPLIED PHARMACOLOGY	human macrophage; endotoxin; air pollution PM10 and PM2.5; phagocytosis; apoptosis; cytokines	NECROSIS-FACTOR-ALPHA; FINE PARTICLES; HOSPITAL ADMISSIONS; RESPIRATORY HEALTH; OXIDATIVE BURST; BLOOD MONOCYTES; CHILDREN; ASTHMA; LIPOPOLYSACCHARIDE; PHAGOCYTOSIS	Inhalation of particulate matter in the ambient air has been shown to cause pulmonary morbidity and exacerbate asthma. Alveolar macrophage (AIM) are essential for effective removal of inhaled particles and microbes in the lower airways. While some particles minimally effect AM function others inhibit antimicrobial activity or cause cytokine and growth factor production leading to inflammation and tissue remodeling. This study has investigated the effects of water soluble (s) and insoluble (is) components of Chapel Hill, North Carolina ambient particulate matter in the size ranges 0.1-2.5 Ccm (PM2.5) and 2.5-10 mum (PM10) diameter, on human AM IL-6, TNF alpha, and MCP-1 cytokine production and host defense mechanisms including phagocytosis and oxidant production. Cytokines were found to be induced by isPM10 to a much higher extent (>50-fold) than sPM10, which in turn stimulated production better than isPM2.5, while sPM2.5 was inactive. Previous studies have indicated that endotoxin (ETOX) is a component of sPM10 responsible for cytokine production. Here, it is shown that inhibition of isPM10-induced cytokine production was partially achieved with polymyxin B and LPS-binding protein (LBP), but not with a metal chelator, implicating ETOX as a cytokine-inducing moiety also in isPM10. In addition to inducing cytokines, exposure to isPM10, but not the other PM fractions, also inhibited phagocytosis and oxidant generation in response to yeast. This inhibition was ETOX independent. The decrease in host defenses may be the result of apoptosis in the AM population, which was also found to be specifically caused by isPM10. These results show that the functional capacity of AM is selectively modulated by insoluble components of coarse PM, including the biocontaminant ETOX.	47	158	2001	7	10.1006/taap.2000.9096	Pharmacology & Pharmacy; Toxicology
Nutrients and foods for the primary prevention of asthma and allergy: Systematic review and meta-analysis. Background: Epidemiologic studies suggest that deficiencies of the nutrients selenium; zinc; vitamins A, C, D, and E; and low fruit and vegetable intake may be associated with the development of asthma and allergic disorders. Objectives: To investigate the evidence that nutrient and food intake modifies the risk of children developing allergy. Methods: We systematically searched 11 databases. Studies were critically appraised, and meta-analyses were undertaken. Results: We identified 62 eligible reports. There were no randomized controlled trials. Studies used cohort (n = 21), case-control (n 5 15), or cross-sectional (n 5 26) designs. All studies were judged to be at moderate to substantial risk of bias. Meta-analysis revealed that serum vitamin A was lower in children with asthma compared with controls (odds ratio [OR], 0.25; 95% CI, 0.10-0.40). Meta-analyses also showed that high maternal dietary vitamin D and E intakes during pregnancy were protective for the development of wheezing outcomes (OR, 0.56, 95% CI, 0.42-0.73; and OR, 0.68, 95% CI, 0.52-0.88, respectively). Adherence to a Mediterranean diet was protective for persistent wheeze (OR, 0.22; 95% CI, 0.08-0.58) and atopy (OR, 0.55; 95% CI, 0.31-0.97). Seventeen of 22 fruit and vegetable studies reported beneficial associations with asthma and allergic outcomes. Results were not supportive for other allergic outcomes for these vitamins or nutrients, or for any outcomes in relation to vitamin C and selenium. Conclusion: The available epidemiologic evidence is weak but nonetheless supportive with respect to vitamins A, D, and E; zinc; fruits and vegetables; and a Mediterranean diet for the prevention of asthma. Experimental studies of these exposures are now warranted. (J Allergy Clin Immunol 2011;127:724-33.). allergy| antioxidants| asthma| atopy| diet| foods| nutrients|vitamin-d intake| mediterranean diet| childhood asthma| school-children| 5-year-old children| risk-factors| respiratory symptoms| antioxidant vitamins| fruit consumption| wheezing symptoms.	MAR-2011	allergy| antioxidants| asthma| atopy| diet| foods| nutrients|vitamin-d intake| mediterranean diet| childhood asthma| school-children| 5-year-old children| risk-factors| respiratory symptoms| antioxidant vitamins| fruit consumption| wheezing symptoms	Nurmatov, U; Devereux, G; Sheikh, A	Nutrients and foods for the primary prevention of asthma and allergy: Systematic review and meta-analysis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergy; antioxidants; asthma; atopy; diet; foods; nutrients	VITAMIN-D INTAKE; MEDITERRANEAN DIET; CHILDHOOD ASTHMA; SCHOOL-CHILDREN; 5-YEAR-OLD CHILDREN; RISK-FACTORS; RESPIRATORY SYMPTOMS; ANTIOXIDANT VITAMINS; FRUIT CONSUMPTION; WHEEZING SYMPTOMS	Background: Epidemiologic studies suggest that deficiencies of the nutrients selenium; zinc; vitamins A, C, D, and E; and low fruit and vegetable intake may be associated with the development of asthma and allergic disorders. Objectives: To investigate the evidence that nutrient and food intake modifies the risk of children developing allergy. Methods: We systematically searched 11 databases. Studies were critically appraised, and meta-analyses were undertaken. Results: We identified 62 eligible reports. There were no randomized controlled trials. Studies used cohort (n = 21), case-control (n 5 15), or cross-sectional (n 5 26) designs. All studies were judged to be at moderate to substantial risk of bias. Meta-analysis revealed that serum vitamin A was lower in children with asthma compared with controls (odds ratio [OR], 0.25; 95% CI, 0.10-0.40). Meta-analyses also showed that high maternal dietary vitamin D and E intakes during pregnancy were protective for the development of wheezing outcomes (OR, 0.56, 95% CI, 0.42-0.73; and OR, 0.68, 95% CI, 0.52-0.88, respectively). Adherence to a Mediterranean diet was protective for persistent wheeze (OR, 0.22; 95% CI, 0.08-0.58) and atopy (OR, 0.55; 95% CI, 0.31-0.97). Seventeen of 22 fruit and vegetable studies reported beneficial associations with asthma and allergic outcomes. Results were not supportive for other allergic outcomes for these vitamins or nutrients, or for any outcomes in relation to vitamin C and selenium. Conclusion: The available epidemiologic evidence is weak but nonetheless supportive with respect to vitamins A, D, and E; zinc; fruits and vegetables; and a Mediterranean diet for the prevention of asthma. Experimental studies of these exposures are now warranted. (J Allergy Clin Immunol 2011;127:724-33.)	85	157	2011	40	10.1016/j.jaci.2010.11.001	Allergy; Immunology
From atopic dermatitis to asthma: the atopic march. Objective: To examine the mechanisms whereby allergen exposure through the epidermis could initiate systemic allergy and predispose individuals to the development of 1 or more atopic diseases via the so-called atopic march. Data Sources: PubMed databases from 1950 to the present were searched for relevant articles pertaining to epidemiologic and genetic evidence of the progression of the atopic march. Study Selection: Articles concerning pathophysiologic conditions that link atopic dermatitis, allergic rhinitis, and asthma were examined. Results: The data suggest that a sequence of atopic manifestations occurs, typically atopic dermatitis in infancy followed by allergic rhinitis and/or asthma in later stages. Reduced filaggrin expression is implicated as a major predisposing factor for atopy in multiple lines of evidence, including genome-wide analysis and microarray investigations. Other gene products have an important role. Cross-sectional and longitudinal studies provide preliminary epidemiologic support for the sequential development of allergic diseases. Conclusion: The mechanisms by which allergen exposure through the epidermis can initiate systemic allergy and predispose individuals to atopic dermatitis, allergic rhinitis, and asthma have become clearer in recent years. Longitudinal studies of individuals carrying loss-of-function filaggrin gene mutations are needed to further define the risks associated with epidermal barrier dysfunction and potentially identify specific targets for barrier repair and prevention of atopic dermatitis and other atopic disease. The effects of preventive and treatment strategies have been inconsistent across studies, and further research is warranted before any definitive recommendations can be made. Ann Allergy Asthma Immunol. 2010; 105:99-106.. of-function mutations| major risk-factor| follow-up| inhaled corticosteroids| airway inflammation| russian karelia| young-children| peanut allergy| phase-iii| filaggrin.	AUG-2010	of-function mutations| major risk-factor| follow-up| inhaled corticosteroids| airway inflammation| russian karelia| young-children| peanut allergy| phase-iii| filaggrin	Spergel, JM	From atopic dermatitis to asthma: the atopic march		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		OF-FUNCTION MUTATIONS; MAJOR RISK-FACTOR; FOLLOW-UP; INHALED CORTICOSTEROIDS; AIRWAY INFLAMMATION; RUSSIAN KARELIA; YOUNG-CHILDREN; PEANUT ALLERGY; PHASE-III; FILAGGRIN	Objective: To examine the mechanisms whereby allergen exposure through the epidermis could initiate systemic allergy and predispose individuals to the development of 1 or more atopic diseases via the so-called atopic march. Data Sources: PubMed databases from 1950 to the present were searched for relevant articles pertaining to epidemiologic and genetic evidence of the progression of the atopic march. Study Selection: Articles concerning pathophysiologic conditions that link atopic dermatitis, allergic rhinitis, and asthma were examined. Results: The data suggest that a sequence of atopic manifestations occurs, typically atopic dermatitis in infancy followed by allergic rhinitis and/or asthma in later stages. Reduced filaggrin expression is implicated as a major predisposing factor for atopy in multiple lines of evidence, including genome-wide analysis and microarray investigations. Other gene products have an important role. Cross-sectional and longitudinal studies provide preliminary epidemiologic support for the sequential development of allergic diseases. Conclusion: The mechanisms by which allergen exposure through the epidermis can initiate systemic allergy and predispose individuals to atopic dermatitis, allergic rhinitis, and asthma have become clearer in recent years. Longitudinal studies of individuals carrying loss-of-function filaggrin gene mutations are needed to further define the risks associated with epidermal barrier dysfunction and potentially identify specific targets for barrier repair and prevention of atopic dermatitis and other atopic disease. The effects of preventive and treatment strategies have been inconsistent across studies, and further research is warranted before any definitive recommendations can be made. Ann Allergy Asthma Immunol. 2010; 105:99-106.	54	157	2010	9	10.1016/j.anai.2009.10.002	Allergy; Immunology
Allergic Bronchopulmonary Aspergillosis. Allergic bronchopulmonary aspergillosis (ABPA) is air immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. Clinically, a patient presents with chronic asthma, recurrent pulmonary infiltrates, and bronchiectasis. The population prevalence of ABPA is not clearly known, but the prevalence in asthma clinics is reported to be around 13%. The disorder needs to be detected before bronchiectasis has developed because the occurrence of bronchiectasis is associated with poorer outcomes. Because many patients with ABPA may be minimally symptomatic or asymptomatic, a high index of suspicion for ABPA should be maintained while managing any patient with bronchial asthma whatever the severity or the level of control. This underscores the need for routine screening of all patients with asthma with an Aspergillus skin test. Finally, there is a need to update and revise the criteria for the diagnosis of ABPA. This review summarizes the advances in the diagnosis and management of ABPA using a systematic search methodology. (CHEST 2009; 135:805-826). allergic bronchopulmonary aspergillosis| aspergillus| bronchial asthma| cystic fibrosis| prevalence|cystic-fibrosis patients| term follow-up| invasive pulmonary aspergillosis| regulator gene-mutations| high-attenuation mucus| fungal disease| recombinant allergens| fumigatus allergens| asthmatic-patients| serum ige.	MAR-2009	allergic bronchopulmonary aspergillosis| aspergillus| bronchial asthma| cystic fibrosis| prevalence|cystic-fibrosis patients| term follow-up| invasive pulmonary aspergillosis| regulator gene-mutations| high-attenuation mucus| fungal disease| recombinant allergens| fumigatus allergens| asthmatic-patients| serum ige	Agarwal, R	Allergic Bronchopulmonary Aspergillosis		CHEST	allergic bronchopulmonary aspergillosis; Aspergillus; bronchial asthma; cystic fibrosis; prevalence	CYSTIC-FIBROSIS PATIENTS; TERM FOLLOW-UP; INVASIVE PULMONARY ASPERGILLOSIS; REGULATOR GENE-MUTATIONS; HIGH-ATTENUATION MUCUS; FUNGAL DISEASE; RECOMBINANT ALLERGENS; FUMIGATUS ALLERGENS; ASTHMATIC-PATIENTS; SERUM IGE	Allergic bronchopulmonary aspergillosis (ABPA) is air immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. Clinically, a patient presents with chronic asthma, recurrent pulmonary infiltrates, and bronchiectasis. The population prevalence of ABPA is not clearly known, but the prevalence in asthma clinics is reported to be around 13%. The disorder needs to be detected before bronchiectasis has developed because the occurrence of bronchiectasis is associated with poorer outcomes. Because many patients with ABPA may be minimally symptomatic or asymptomatic, a high index of suspicion for ABPA should be maintained while managing any patient with bronchial asthma whatever the severity or the level of control. This underscores the need for routine screening of all patients with asthma with an Aspergillus skin test. Finally, there is a need to update and revise the criteria for the diagnosis of ABPA. This review summarizes the advances in the diagnosis and management of ABPA using a systematic search methodology. (CHEST 2009; 135:805-826)	242	157	2009	22	10.1378/chest.08-2586	General & Internal Medicine; Respiratory System
Air pollution and child respiratory health - A case-crossover study in Australia and new Zealand. Rationale: The strength of the association between outdoor air pollution and hospital admissions in children has not yet been well defined. Objectives: To estimate the impact of outdoor air pollution on respiratory morbidity in children after controlling for the confounding effects of weather, season, and other pollutants. Methods: The study used data on respiratory hospital admissions in children (three age groups: < 1, 1-4, and 5-14years) for five cities in Australia and two in New Zealand. Time series of daily numbers of hospital admissions were analyzed using the case-crossover method; the results from cities were combined using a random-effects meta-analysis. Measurements and Main Results: Significant increases across the cities were observed for hospital admissions in children for pneumonia and acute bronchitis (0, 1-4 years), respiratory disease (0, 1-4, 5-14 years), and asthma (5-14 years). These increases were found for particulate matter with a diameter less than 2.5 mu m (PM2.5) and less than 10 mu m (PM10), nephelometry, NO2, and SO2. The largest association found was a 6.0% increase in asthma admissions (5-14years) in relation to a 5.1-ppb increase in 24-hour NO2. Conclusions: This study found strong and consistent associations between outdoor air pollution and short-term increases in childhood hospital admissions. A number of different pollutants showed significant associations, and these were distinct from any temperature (warm or cool) effects.. air pollutants| australasia| meta-analysis| respiration disorders|infant-mortality| utah valley| association| disease| metaanalysis| pollutants| admissions| particles| selection| asthma.	JUN 1-2005	air pollutants| australasia| meta-analysis| respiration disorders|infant-mortality| utah valley| association| disease| metaanalysis| pollutants| admissions| particles| selection| asthma	Barnett, AG; Williams, GM; Schwartz, J; Neller, AH; Best, TL; Petroeschevsky, AL; Simpson, RW	Air pollution and child respiratory health - A case-crossover study in Australia and new Zealand		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	air pollutants; Australasia; meta-analysis; respiration disorders	INFANT-MORTALITY; UTAH VALLEY; ASSOCIATION; DISEASE; METAANALYSIS; POLLUTANTS; ADMISSIONS; PARTICLES; SELECTION; ASTHMA	Rationale: The strength of the association between outdoor air pollution and hospital admissions in children has not yet been well defined. Objectives: To estimate the impact of outdoor air pollution on respiratory morbidity in children after controlling for the confounding effects of weather, season, and other pollutants. Methods: The study used data on respiratory hospital admissions in children (three age groups: < 1, 1-4, and 5-14years) for five cities in Australia and two in New Zealand. Time series of daily numbers of hospital admissions were analyzed using the case-crossover method; the results from cities were combined using a random-effects meta-analysis. Measurements and Main Results: Significant increases across the cities were observed for hospital admissions in children for pneumonia and acute bronchitis (0, 1-4 years), respiratory disease (0, 1-4, 5-14 years), and asthma (5-14 years). These increases were found for particulate matter with a diameter less than 2.5 mu m (PM2.5) and less than 10 mu m (PM10), nephelometry, NO2, and SO2. The largest association found was a 6.0% increase in asthma admissions (5-14years) in relation to a 5.1-ppb increase in 24-hour NO2. Conclusions: This study found strong and consistent associations between outdoor air pollution and short-term increases in childhood hospital admissions. A number of different pollutants showed significant associations, and these were distinct from any temperature (warm or cool) effects.	30	157	2005	7	10.1164/rccm.200411-1586OC	General & Internal Medicine; Respiratory System
Dietary prevention of allergic diseases in infants and small children - Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations. The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.. breast feeding| cow's milk allergy| food allergy| prevention| review| statements of evidence|high-risk infants| partial whey hydrolysate| brief neonatal exposure| breast-fed infants| cows milk formula| atopic disease| follow-up| 1st year| controlled-trial| preterm infants.	AUG-2004	breast feeding| cow's milk allergy| food allergy| prevention| review| statements of evidence|high-risk infants| partial whey hydrolysate| brief neonatal exposure| breast-fed infants| cows milk formula| atopic disease| follow-up| 1st year| controlled-trial| preterm infants	Muraro, A; Dreborg, S; Halken, S; Host, A; Niggemann, B; Aalberse, R; Arshad, SH; von Berg, A; Carlsen, KH; Duschen, K; Eigenmann, P; Hill, D; Jones, C; Mellon, M; Oldeus, G; Oranje, A; Pascual, C; Prescott, S; Sampson, H; Svartengren, M; Vandenplas, Y; Wahn, U; Warner, JA; Warner, JO; Wickman, M; Zeiger, RS	Dietary prevention of allergic diseases in infants and small children - Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations		PEDIATRIC ALLERGY AND IMMUNOLOGY	breast feeding; cow's milk allergy; food allergy; prevention; review; statements of evidence	HIGH-RISK INFANTS; PARTIAL WHEY HYDROLYSATE; BRIEF NEONATAL EXPOSURE; BREAST-FED INFANTS; COWS MILK FORMULA; ATOPIC DISEASE; FOLLOW-UP; 1ST YEAR; CONTROLLED-TRIAL; PRETERM INFANTS	The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.	83	157	2004	17	10.1111/j.1399-3038.2004.00127.x	Allergy; Immunology; Pediatrics
Alternaria-induced asthma. Acute, severe asthma attacks can be precipitated by a variety of stimuli including exposure to aeroallergens, viral respiratory infections, pollutants, and occupational chemicals. Alternaria is a major aeroallergen in many parts of the world. Sensitivity to Alternaria has been increasingly recognized as a risk factor for the development and persistence of asthma, asthma severity, and potentially fatal asthma exacerbations. We present the case of a patient with IgE-mediated sensitivity to Alternaria who developed an acute, life-threatening asthma attack during the peak Alternaria season. We describe the aerobiology, pathophysiobiology, diagnosis, and treatment options for patients with Alternaria-induced asthma.. alternaria| asthma| allergens| aerobiology|humanized monoclonal-antibody| nutrition examination survey| school-age-children| 2nd national-health| house-dust mite| fungal allergens| childhood asthma| molecular-cloning| ige antibody| risk-factor.	FEB-2004	alternaria| asthma| allergens| aerobiology|humanized monoclonal-antibody| nutrition examination survey| school-age-children| 2nd national-health| house-dust mite| fungal allergens| childhood asthma| molecular-cloning| ige antibody| risk-factor	Bush, RK; Prochnau, JJ	Alternaria-induced asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	alternaria; asthma; allergens; aerobiology	HUMANIZED MONOCLONAL-ANTIBODY; NUTRITION EXAMINATION SURVEY; SCHOOL-AGE-CHILDREN; 2ND NATIONAL-HEALTH; HOUSE-DUST MITE; FUNGAL ALLERGENS; CHILDHOOD ASTHMA; MOLECULAR-CLONING; IGE ANTIBODY; RISK-FACTOR	Acute, severe asthma attacks can be precipitated by a variety of stimuli including exposure to aeroallergens, viral respiratory infections, pollutants, and occupational chemicals. Alternaria is a major aeroallergen in many parts of the world. Sensitivity to Alternaria has been increasingly recognized as a risk factor for the development and persistence of asthma, asthma severity, and potentially fatal asthma exacerbations. We present the case of a patient with IgE-mediated sensitivity to Alternaria who developed an acute, life-threatening asthma attack during the peak Alternaria season. We describe the aerobiology, pathophysiobiology, diagnosis, and treatment options for patients with Alternaria-induced asthma.	51	157	2004	8	10.1016/j.jaci.2003.11.023	Allergy; Immunology
The occupational burden of chronic obstructive pulmonary disease. Although chronic obstructive pulmonary disease (COPD) is attributed predominantly to tobacco smoke, occupational exposures are also suspected risk factors for COPD. Estimating the proportion of COPD attributable to occupation is thus an important public health need. A randomly selected sample of 2,061 US residents aged 55-75 yrs completed telephone interviews covering respiratory health, general health status and occupational history. Occupational exposure during the longest-held job was determined by self-reported exposure to vapours, gas, dust or fumes and through a job exposure matrix. COPD was defined by self-reported physician's diagnosis. After adjusting for smoking status and demography, the odds ratio for COPD related to self-reported occupational exposure was 2.0 (95% confidence interval (Cl) 1.6-2.5), resulting in an adjusted population attributable risk (PAR) of 20% (95% Cl 13-27%). The adjusted odds ratio based on the job exposure matrix was 1.6 (95% Cl 1.1-2.5) for high and 1.4 (95% Cl 1.1-1.9) for intermediate probability of occupational dust exposure; the associated PAR was 9% (95% Cl 3-15%). A narrower definition of COPD, excluding chronic bronchitis, was associated with a PAR based on reported occupational exposure of 31% (95% Cl 19-41%). Past occupational exposures significantly increased the likelihood of chronic obstructive pulmonary disease, independent of the effects of smoking. Given that one in five cases of chronic obstructive pulmonary disease may be attributable to occupational exposures, clinicians and health policy-makers should address this potential avenue of chronic obstructive pulmonary disease causation and its prevention.. airflow limitation| chronic bronchitis| chronic obstructive pulmonary disease| emphysema| occupational health| work-related|chronic respiratory symptoms| lung-function| chronic-bronchitis| general-population| exposures| adults| prevalence| community| asthma| miners.	SEP-2003	airflow limitation| chronic bronchitis| chronic obstructive pulmonary disease| emphysema| occupational health| work-related|chronic respiratory symptoms| lung-function| chronic-bronchitis| general-population| exposures| adults| prevalence| community| asthma| miners	Trupin, L; Earnest, G; San Pedro, M; Balmes, JR; Eisner, MD; Yelin, E; Katz, PP; Blanc, PD	The occupational burden of chronic obstructive pulmonary disease		EUROPEAN RESPIRATORY JOURNAL	Airflow limitation; chronic bronchitis; chronic obstructive pulmonary disease; emphysema; occupational health; work-related	CHRONIC RESPIRATORY SYMPTOMS; LUNG-FUNCTION; CHRONIC-BRONCHITIS; GENERAL-POPULATION; EXPOSURES; ADULTS; PREVALENCE; COMMUNITY; ASTHMA; MINERS	Although chronic obstructive pulmonary disease (COPD) is attributed predominantly to tobacco smoke, occupational exposures are also suspected risk factors for COPD. Estimating the proportion of COPD attributable to occupation is thus an important public health need. A randomly selected sample of 2,061 US residents aged 55-75 yrs completed telephone interviews covering respiratory health, general health status and occupational history. Occupational exposure during the longest-held job was determined by self-reported exposure to vapours, gas, dust or fumes and through a job exposure matrix. COPD was defined by self-reported physician's diagnosis. After adjusting for smoking status and demography, the odds ratio for COPD related to self-reported occupational exposure was 2.0 (95% confidence interval (Cl) 1.6-2.5), resulting in an adjusted population attributable risk (PAR) of 20% (95% Cl 13-27%). The adjusted odds ratio based on the job exposure matrix was 1.6 (95% Cl 1.1-2.5) for high and 1.4 (95% Cl 1.1-1.9) for intermediate probability of occupational dust exposure; the associated PAR was 9% (95% Cl 3-15%). A narrower definition of COPD, excluding chronic bronchitis, was associated with a PAR based on reported occupational exposure of 31% (95% Cl 19-41%). Past occupational exposures significantly increased the likelihood of chronic obstructive pulmonary disease, independent of the effects of smoking. Given that one in five cases of chronic obstructive pulmonary disease may be attributable to occupational exposures, clinicians and health policy-makers should address this potential avenue of chronic obstructive pulmonary disease causation and its prevention.	34	157	2003	8	10.1183/09031936.03.00094203	Respiratory System
Molecular basis of arthropod cross-reactivity: IgE-binding cross-reactive epitopes of shrimp, house dust mite and cockroach tropomyosins. Background. Shrimp may cross-react with other crustaceans and mollusks and nonedible arthropods such as insects (cockroach and chironomids), arachnids (house dust mites) and even nematodes. Since the muscle protein tropomyosin has been implicated as a possible cross-reacting allergen, this study characterized the IgE-binding epitopes in shrimp tropomyosin, Pen a 1, that cross-react with other allergenic invertebrate tropomyosins in house dust mites (Der p 10, Der f 10) and cockroaches (Per a 7). Pen a 1-reactive sera from shrimp-allergic subjects were used to evaluate the effect on IgE binding of different amino acid substitutions in Pen a 1 epitopes based on homologous sequences in Per a 7 and Der p 10/Der f 10. Methods: Peptides were synthesized spanning the length of Pen a 1 IgE-binding epitopes and amino acid substitutions were performed based on homologous amino acid sequences from Per a 7 and Der p 10/Der f 10. Results: 7/8 individually recognized Pen a 1 epitopes (2, 3a, 3b, 4, 5a, 5b and 56 had an identical amino acid sequence with lobster allergen, Hom a 1, 4/8 (3a, 3b, 4 and 5a) with Der p 10 and Derf 10, and 5/8 (2, 3a, 3b, 4 and 5a) with Per a 7. In addition, even homologous regions of other arthropod tropomyosins that differ in one or more amino acids from the sequences of Pen a 1 epitopes are still recognized by shrimp-allergic IgE antibodies. In total, shrimp-allergic sera recognize 6/8 peptides homologous to Pen a 1 epitopes in Per a 7, 7/8 in Der p 10/Der f 10, and 7/8 epitopes in Hom a 1. Conclusions: The IgE recognition by shrimp-allergic individuals of identified and/or similar amino acid sequences homologous to Pen a 1 epitopes in mite, cockroach and lobster tropomyosins are the basis of the in vitro cross-reactivity among invertebrate species. Based on amino acid sequence similarity and epitope reactivity, lobster tropomyosin has the strongest and cockroach the least cross-reactivity with shrimp. The clinical relevance of these cross-reactivities in developing allergic reactions to different arthropods needs to be determined. Copyright (C) 2002 S. Karger AG, Basel.. shrimp| dust mite| cockroach| allergens| cross-reactivity|muscle protein tropomyosin| major allergen| food hypersensitivity| occupational asthma| mutational analysis| identification| immunotherapy| pollen| lobster| sensitization.	SEP-2002	shrimp| dust mite| cockroach| allergens| cross-reactivity|muscle protein tropomyosin| major allergen| food hypersensitivity| occupational asthma| mutational analysis| identification| immunotherapy| pollen| lobster| sensitization	Ayuso, R; Reese, G; Leong-Kee, S; Plante, M; Lehrer, SB	Molecular basis of arthropod cross-reactivity: IgE-binding cross-reactive epitopes of shrimp, house dust mite and cockroach tropomyosins		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	shrimp; dust mite; cockroach; allergens; cross-reactivity	MUSCLE PROTEIN TROPOMYOSIN; MAJOR ALLERGEN; FOOD HYPERSENSITIVITY; OCCUPATIONAL ASTHMA; MUTATIONAL ANALYSIS; IDENTIFICATION; IMMUNOTHERAPY; POLLEN; LOBSTER; SENSITIZATION	Background. Shrimp may cross-react with other crustaceans and mollusks and nonedible arthropods such as insects (cockroach and chironomids), arachnids (house dust mites) and even nematodes. Since the muscle protein tropomyosin has been implicated as a possible cross-reacting allergen, this study characterized the IgE-binding epitopes in shrimp tropomyosin, Pen a 1, that cross-react with other allergenic invertebrate tropomyosins in house dust mites (Der p 10, Der f 10) and cockroaches (Per a 7). Pen a 1-reactive sera from shrimp-allergic subjects were used to evaluate the effect on IgE binding of different amino acid substitutions in Pen a 1 epitopes based on homologous sequences in Per a 7 and Der p 10/Der f 10. Methods: Peptides were synthesized spanning the length of Pen a 1 IgE-binding epitopes and amino acid substitutions were performed based on homologous amino acid sequences from Per a 7 and Der p 10/Der f 10. Results: 7/8 individually recognized Pen a 1 epitopes (2, 3a, 3b, 4, 5a, 5b and 56 had an identical amino acid sequence with lobster allergen, Hom a 1, 4/8 (3a, 3b, 4 and 5a) with Der p 10 and Derf 10, and 5/8 (2, 3a, 3b, 4 and 5a) with Per a 7. In addition, even homologous regions of other arthropod tropomyosins that differ in one or more amino acids from the sequences of Pen a 1 epitopes are still recognized by shrimp-allergic IgE antibodies. In total, shrimp-allergic sera recognize 6/8 peptides homologous to Pen a 1 epitopes in Per a 7, 7/8 in Der p 10/Der f 10, and 7/8 epitopes in Hom a 1. Conclusions: The IgE recognition by shrimp-allergic individuals of identified and/or similar amino acid sequences homologous to Pen a 1 epitopes in mite, cockroach and lobster tropomyosins are the basis of the in vitro cross-reactivity among invertebrate species. Based on amino acid sequence similarity and epitope reactivity, lobster tropomyosin has the strongest and cockroach the least cross-reactivity with shrimp. The clinical relevance of these cross-reactivities in developing allergic reactions to different arthropods needs to be determined. Copyright (C) 2002 S. Karger AG, Basel.	57	157	2002	11	10.1159/000065172	Allergy; Immunology
Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Background and Objective. There seems to be a strong causal relationship between allergy and the origins of asthma. Susceptibility to both is determined by a combination of genetics and environment acting through a complex network of cytokines. Nearly 90% of affected children have positive skin tests indicating the presence of specific immunoglobulin E (IgE), with sensitivity to house dust mite, Alternaria, cockroach, cat, and dog most closely linked to the disease. Greater exposure to house dust mite during infancy leads to earlier onset of wheezing, and elevated serum IgE levels correlate with the appearance of asthma symptoms. Specific IgE binds to high-affinity (Fc epsilon RI) receptors on mast cells and basophils. The IgE-mediated reactions that follow exposure of sensitized mast cells to an allergen are designated early- and late-phase asthmatic responses (EAR and LAR). EAR is characterized by release of histamine and other preformed mediators within 1 hour of allergen exposure. It is often followed by LAR, an infiltration of the airways by inflammatory cells associated with an episode of more prolonged, and usually more severe airflow obstruction, 4 to 8 hours after antigen exposure. Chronic airway symptoms result from persistent LAR caused by continuous allergen exposure. IgE antibodies are capable of passive transfer of both EAR and LAR sensitivity. IgE-mediated mast cell activation contributes to chronic tissue eosinophilia and airway remodeling, with permanent loss in pulmonary function. Omalizumab (rhuMAb-E25) is a recombinant, humanized, monoclonal anti-IgE antibody of mouse origin developed for the treatment of IgE-mediated diseases. Omalizumab binds to free IgE at the same site as the high-affinity receptor. Although it attaches to free IgE, it does not bind to IgA, IgG, or cell-bound IgE. It therefore does not induce cross-linking of cell-bound IgE, which would lead to the release of allergic mediators. It has been reported to decrease serum IgE levels in a dose-dependent manner, inhibit EAR and LAR, and cause a down-regulation of Fc epsilon RI receptors on basophils. Omalizumab has been reported to be safe and effective in improving asthma control and reducing the requirement for oral and inhaled corticosteroids. This double-blind, randomized, placebo-controlled study evaluated the safety, steroid-sparing effects, and impact on disease exacerbations of omalizumab in the treatment of childhood asthma. Methods. Participants were 334 males and premenarchal females aged 6 to 12 years, with moderate to severe allergic asthma requiring treatment with inhaled corticosteroids. During a run-in phase, all children were switched to equivalent doses of beclomethasone dipropionate (BDP), and the dose was adjusted to assure maintenance of asthma control achieved with previous corticosteroid treatment. Children were randomized to subcutaneously administered placebo (N = 109) or omalizumab (N = 225) at a dose based on body weight and initial serum IgE (0.016 mg/kg/IgE [IU/mL] per 4 weeks). BDP dose (initial range 168-420 mug/d) was kept stable for 16 weeks (stable-steroid phase), reduced over 8 weeks to the minimum effective dose (steroid-reduction phase), and maintained constant for the final 4 weeks. Results. More participants in the omalizumab group decreased their BDP dose, and their reduction was greater than that of the placebo group (median reduction 100% vs 66.7%). BDP was withdrawn completely in 55% of the omalizumab group versus 39% of the placebo group. The incidence and the frequency of asthma exacerbations requiring treatment with doubling of BDP dose or systemic corticosteroids were lower in the omalizumab group. The treatment differences were statistically significant during the steroid-reduction phase, during which fewer participants in the omalizumab group had asthma exacerbation episodes (18.2% vs 38.5%), and the mean number of episodes per patient was smaller than with placebo (0.42 vs 2.72). Five asthma exacerbations requiring hospitalization all occurred in the placebo group. Participants' and investigators' global evaluations of treatment effectiveness were more favorable for omalizumab than placebo. Investigators rated effectiveness excellent for 31.5% of the omalizumab group versus 16.3% of the placebo group and good for 44.7% of the omalizumab group versus 32.7% of the placebo group. There was little change in asthma symptom scores or spirometry measurements during either the stable-steroid or steroid dose-reduction phase, with minimal differences between the treatment groups. The requirement for rescue medication in the omalizumab group during both the stable-steroid and steroid dose-reduction phases was consistently lower than at baseline. At week 28, the median number of puffs of rescue medication taken daily was 0 in the omalizumab group and 0.46 in the placebo group. The change from baseline was significant in favor of omalizumab. Over the entire treatment period, patients in the omalizumab group missed a mean of 0.65 school days, compared with a mean of 1.21 days in the placebo group. The mean number of unscheduled medical contacts attributable to asthma-related medical problems was significantly smaller in the omalizumab group than in the placebo group throughout the treatment period (0.15 vs 5.35). Median reduction in serum free IgE was 95% to 99% among omalizumab patients. Median free IgE ranged from 133 to 790 IU/mL at baseline and was in the range of 6 to 9 IU/mL during the treatment period. The dosing scheme used in the trial therefore effectively reduced serum IgE in patients with initial concentrations as high as 1300 IU/mL. There was no reduction in free IgE in the placebo group. Omalizumab treatment was well tolerated. There were no serious treatment-related adverse events. The frequency and types of all adverse events were similar in the omalizumab and placebo groups. The majority of adverse events were mild to moderate in severity. No adverse events suggestive of serum sickness or immune complex formation were observed. Study-drug-related adverse events occurred more frequently in the omalizumab group than in the placebo group (6.2% vs 0.9%). Urticaria was reported in 9 omalizumab patients (4%) compared with 1 (0.9%) placebo patient and was mild or moderate in nearly all cases. Conclusion. Treatment with omalizumab is safe in children with asthma. It reduces the requirement for inhaled corticosteroids while protecting against disease exacerbation.. asthma| child| omalizumab| rhumab-e25| anti-ige| beclomethasone dipropionate| steroid-sparing| inhaled corticosteroid| asthma exacerbation|ige monoclonal-antibody| airway hyperresponsiveness| fluticasone propionate| pulmonary-function| allergic rhinitis| complex-formation| sensitization| association| children| exposure.	AUG-2001	asthma| child| omalizumab| rhumab-e25| anti-ige| beclomethasone dipropionate| steroid-sparing| inhaled corticosteroid| asthma exacerbation|ige monoclonal-antibody| airway hyperresponsiveness| fluticasone propionate| pulmonary-function| allergic rhinitis| complex-formation| sensitization| association| children| exposure	Milgrom, H; Berger, W; Nayak, A; Gupta, N; Pollard, S; McAlary, M; Taylor, AF; Rohane, P	Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab)		PEDIATRICS	asthma; child; omalizumab; rhuMAb-E25; anti-IgE; beclomethasone dipropionate; steroid-sparing; inhaled corticosteroid; asthma exacerbation	IGE MONOCLONAL-ANTIBODY; AIRWAY HYPERRESPONSIVENESS; FLUTICASONE PROPIONATE; PULMONARY-FUNCTION; ALLERGIC RHINITIS; COMPLEX-FORMATION; SENSITIZATION; ASSOCIATION; CHILDREN; EXPOSURE	Background and Objective. There seems to be a strong causal relationship between allergy and the origins of asthma. Susceptibility to both is determined by a combination of genetics and environment acting through a complex network of cytokines. Nearly 90% of affected children have positive skin tests indicating the presence of specific immunoglobulin E (IgE), with sensitivity to house dust mite, Alternaria, cockroach, cat, and dog most closely linked to the disease. Greater exposure to house dust mite during infancy leads to earlier onset of wheezing, and elevated serum IgE levels correlate with the appearance of asthma symptoms. Specific IgE binds to high-affinity (Fc epsilon RI) receptors on mast cells and basophils. The IgE-mediated reactions that follow exposure of sensitized mast cells to an allergen are designated early- and late-phase asthmatic responses (EAR and LAR). EAR is characterized by release of histamine and other preformed mediators within 1 hour of allergen exposure. It is often followed by LAR, an infiltration of the airways by inflammatory cells associated with an episode of more prolonged, and usually more severe airflow obstruction, 4 to 8 hours after antigen exposure. Chronic airway symptoms result from persistent LAR caused by continuous allergen exposure. IgE antibodies are capable of passive transfer of both EAR and LAR sensitivity. IgE-mediated mast cell activation contributes to chronic tissue eosinophilia and airway remodeling, with permanent loss in pulmonary function. Omalizumab (rhuMAb-E25) is a recombinant, humanized, monoclonal anti-IgE antibody of mouse origin developed for the treatment of IgE-mediated diseases. Omalizumab binds to free IgE at the same site as the high-affinity receptor. Although it attaches to free IgE, it does not bind to IgA, IgG, or cell-bound IgE. It therefore does not induce cross-linking of cell-bound IgE, which would lead to the release of allergic mediators. It has been reported to decrease serum IgE levels in a dose-dependent manner, inhibit EAR and LAR, and cause a down-regulation of Fc epsilon RI receptors on basophils. Omalizumab has been reported to be safe and effective in improving asthma control and reducing the requirement for oral and inhaled corticosteroids. This double-blind, randomized, placebo-controlled study evaluated the safety, steroid-sparing effects, and impact on disease exacerbations of omalizumab in the treatment of childhood asthma. Methods. Participants were 334 males and premenarchal females aged 6 to 12 years, with moderate to severe allergic asthma requiring treatment with inhaled corticosteroids. During a run-in phase, all children were switched to equivalent doses of beclomethasone dipropionate (BDP), and the dose was adjusted to assure maintenance of asthma control achieved with previous corticosteroid treatment. Children were randomized to subcutaneously administered placebo (N = 109) or omalizumab (N = 225) at a dose based on body weight and initial serum IgE (0.016 mg/kg/IgE [IU/mL] per 4 weeks). BDP dose (initial range 168-420 mug/d) was kept stable for 16 weeks (stable-steroid phase), reduced over 8 weeks to the minimum effective dose (steroid-reduction phase), and maintained constant for the final 4 weeks. Results. More participants in the omalizumab group decreased their BDP dose, and their reduction was greater than that of the placebo group (median reduction 100% vs 66.7%). BDP was withdrawn completely in 55% of the omalizumab group versus 39% of the placebo group. The incidence and the frequency of asthma exacerbations requiring treatment with doubling of BDP dose or systemic corticosteroids were lower in the omalizumab group. The treatment differences were statistically significant during the steroid-reduction phase, during which fewer participants in the omalizumab group had asthma exacerbation episodes (18.2% vs 38.5%), and the mean number of episodes per patient was smaller than with placebo (0.42 vs 2.72). Five asthma exacerbations requiring hospitalization all occurred in the placebo group. Participants' and investigators' global evaluations of treatment effectiveness were more favorable for omalizumab than placebo. Investigators rated effectiveness excellent for 31.5% of the omalizumab group versus 16.3% of the placebo group and good for 44.7% of the omalizumab group versus 32.7% of the placebo group. There was little change in asthma symptom scores or spirometry measurements during either the stable-steroid or steroid dose-reduction phase, with minimal differences between the treatment groups. The requirement for rescue medication in the omalizumab group during both the stable-steroid and steroid dose-reduction phases was consistently lower than at baseline. At week 28, the median number of puffs of rescue medication taken daily was 0 in the omalizumab group and 0.46 in the placebo group. The change from baseline was significant in favor of omalizumab. Over the entire treatment period, patients in the omalizumab group missed a mean of 0.65 school days, compared with a mean of 1.21 days in the placebo group. The mean number of unscheduled medical contacts attributable to asthma-related medical problems was significantly smaller in the omalizumab group than in the placebo group throughout the treatment period (0.15 vs 5.35). Median reduction in serum free IgE was 95% to 99% among omalizumab patients. Median free IgE ranged from 133 to 790 IU/mL at baseline and was in the range of 6 to 9 IU/mL during the treatment period. The dosing scheme used in the trial therefore effectively reduced serum IgE in patients with initial concentrations as high as 1300 IU/mL. There was no reduction in free IgE in the placebo group. Omalizumab treatment was well tolerated. There were no serious treatment-related adverse events. The frequency and types of all adverse events were similar in the omalizumab and placebo groups. The majority of adverse events were mild to moderate in severity. No adverse events suggestive of serum sickness or immune complex formation were observed. Study-drug-related adverse events occurred more frequently in the omalizumab group than in the placebo group (6.2% vs 0.9%). Urticaria was reported in 9 omalizumab patients (4%) compared with 1 (0.9%) placebo patient and was mild or moderate in nearly all cases. Conclusion. Treatment with omalizumab is safe in children with asthma. It reduces the requirement for inhaled corticosteroids while protecting against disease exacerbation.	45	157	2001	10	10.1542/peds.108.2.e36	Pediatrics
Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease. We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV1 of < 12% and < 200 ml after 200 mug of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV1 of < 12% but > 200 ml after 200 mug of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.. endogenous nitric-oxide| corticosteroid-therapy| respiratory-tract| single-breath| asthma| copd| inflammation| airway| bronchitis.	NOV-2000	endogenous nitric-oxide| corticosteroid-therapy| respiratory-tract| single-breath| asthma| copd| inflammation| airway| bronchitis	Papi, A; Romagnoli, M; Baraldo, S; Braccioni, F; Guzzinati, I; Saetta, M; Ciaccia, A; Fabbri, LM	Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		ENDOGENOUS NITRIC-OXIDE; CORTICOSTEROID-THERAPY; RESPIRATORY-TRACT; SINGLE-BREATH; ASTHMA; COPD; INFLAMMATION; AIRWAY; BRONCHITIS	We investigated the relationship between the reversibility of airflow limitation, the concentration of nitric oxide (NO) in exhaled air, and the inflammatory cells in the sputum of patients with stable chronic obstructive pulmonary disease (COPD). We examined nine normal healthy control subjects and 20 nonatopic patients with COPD. Ten patients had no reversibility of airflow limitation (increase in FEV1 of < 12% and < 200 ml after 200 mug of inhaled salbutamol), and 10 patients had partial reversibility of airflow limitation (increase in FEV1 of < 12% but > 200 ml after 200 mug of inhaled salbutamol). Exhaled NO levels were higher in COPD patients with partial reversibility of airflow limitation than in those with no reversibility of airflow limitation (median 24 [interquartile range 15.3 to 32] ppb versus 8.9 [4.6 to 14.7] ppb; p < 0.01). Compared with healthy control subjects, only COPD patients with partial reversibility of airflow limitation had increased concentrations of sputum eosinophils. We conclude that, in patients with stable COPD, even a partial bronchodilator response to inhaled salbutamol is associated with increased exhaled NO and sputum eosinophilia, suggesting that these patients may have a different response to treatment than do those without reversible airflow limitation.	35	157	2000	5		General & Internal Medicine; Respiratory System
MMP12, Lung Function, and COPD in High-Risk Populations. BACKGROUND Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease ( COPD), particularly in high-risk groups. METHODS We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV(1)]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV(1) and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD. RESULTS The minor allele ( G) of a functional variant in the promoter region of MMP12 (rs2276109 [-82A -> G]) was positively associated with FEV1 in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2x10(-6)). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P = 0.02) and with a reduced risk of COPD in a cohort of smokers ( odds ratio, 0.63; 95% CI, 0.45 to 0.88; P = 0.005) and among participants in a family-based study of early-onset COPD (P = 0.006). CONCLUSIONS The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers.. obstructive pulmonary-disease| air-flow obstruction| childhood asthma| polymorphisms| emphysema| gene| smokers| decline| growth| association.	DEC 31-2009	obstructive pulmonary-disease| air-flow obstruction| childhood asthma| polymorphisms| emphysema| gene| smokers| decline| growth| association	Hunninghake, GM; Cho, MH; Tesfaigzi, Y; Soto-Quiros, ME; Avila, L; Lasky-Su, J; Stidley, C; Melen, E; Soderhall, C; Hallberg, J; Kull, I; Kere, J; Svartengren, M; Pershagen, G; Wickman, M; Lange, C; Demeo, DL; Hersh, CP; Klanderman, BJ; Raby, BA; Sparrow, D; Shapiro, SD; Silverman, EK; Litonjua, AA; Weiss, ST; Celedon, JC	MMP12, Lung Function, and COPD in High-Risk Populations		NEW ENGLAND JOURNAL OF MEDICINE		OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; CHILDHOOD ASTHMA; POLYMORPHISMS; EMPHYSEMA; GENE; SMOKERS; DECLINE; GROWTH; ASSOCIATION	BACKGROUND Genetic variants influencing lung function in children and adults may ultimately lead to the development of chronic obstructive pulmonary disease ( COPD), particularly in high-risk groups. METHODS We tested for an association between single-nucleotide polymorphisms (SNPs) in the gene encoding matrix metalloproteinase 12 (MMP12) and a measure of lung function (prebronchodilator forced expiratory volume in 1 second [FEV(1)]) in more than 8300 subjects in seven cohorts that included children and adults. Within the Normative Aging Study (NAS), a cohort of initially healthy adult men, we tested for an association between SNPs that were associated with FEV(1) and the time to the onset of COPD. We then examined the relationship between MMP12 SNPs and COPD in two cohorts of adults with COPD or at risk for COPD. RESULTS The minor allele ( G) of a functional variant in the promoter region of MMP12 (rs2276109 [-82A -> G]) was positively associated with FEV1 in a combined analysis of children with asthma and adult former and current smokers in all cohorts (P=2x10(-6)). This allele was also associated with a reduced risk of the onset of COPD in the NAS cohort (hazard ratio, 0.65; 95% confidence interval [CI], 0.46 to 0.92; P = 0.02) and with a reduced risk of COPD in a cohort of smokers ( odds ratio, 0.63; 95% CI, 0.45 to 0.88; P = 0.005) and among participants in a family-based study of early-onset COPD (P = 0.006). CONCLUSIONS The minor allele of a SNP in MMP12 (rs2276109) is associated with a positive effect on lung function in children with asthma and in adults who smoke. This allele is also associated with a reduced risk of COPD in adult smokers.	40	156	2009	10	10.1056/NEJMoa0904006	General & Internal Medicine
Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies. Background Allergen-specific immunotherapy represents a causal form of treatment for IgE-mediated allergies. The allergen extract-based analyses of immunotherapy-induced effects yielded highly controversial results regarding a beneficial role of therapy-induced IgG antibodies. Objective We analysed allergen-specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1-inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5). Results The strong induction of allergen-specific IgG(1) and IgG(4) antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy-induced allergen-specific IgM and IgG(2) responses were also noted in several actively treated patients. An inhibition of allergen-dependent basophil histamine release was only obtained with sera containing therapy-induced allergen-specific IgG, but not with sera obtained before therapy or from placebo-treated patients. Moreover, patients with therapy-induced allergen-specific IgG antibodies showed a reduced induction of allergen-specific IgE responses during seasonal grass pollen exposure. Conclusion Successful immunotherapy with the MPL-adjuvanted grass pollen allergy vaccine is associated with the production of allergen-specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate-type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.. blocking antibodies| immunotherapy| recombinant grass pollen allergens|grass-pollen allergen| hepatitis-b-vaccine| ige| igg2| immunogenicity| immunization| epitopes| efficacy| defects| safety.	SEP-2003	blocking antibodies| immunotherapy| recombinant grass pollen allergens|grass-pollen allergen| hepatitis-b-vaccine| ige| igg2| immunogenicity| immunization| epitopes| efficacy| defects| safety	Mothes, N; Heinzkill, M; Drachenberg, KJ; Sperr, WR; Krauth, MT; Majlesi, Y; Semper, H; Valent, P; Niederberger V; Kraft, D; Valenta, R	Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies		CLINICAL AND EXPERIMENTAL ALLERGY	blocking antibodies; immunotherapy; recombinant grass pollen allergens	GRASS-POLLEN ALLERGEN; HEPATITIS-B-VACCINE; IGE; IGG2; IMMUNOGENICITY; IMMUNIZATION; EPITOPES; EFFICACY; DEFECTS; SAFETY	Background Allergen-specific immunotherapy represents a causal form of treatment for IgE-mediated allergies. The allergen extract-based analyses of immunotherapy-induced effects yielded highly controversial results regarding a beneficial role of therapy-induced IgG antibodies. Objective We analysed allergen-specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1-inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5). Results The strong induction of allergen-specific IgG(1) and IgG(4) antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy-induced allergen-specific IgM and IgG(2) responses were also noted in several actively treated patients. An inhibition of allergen-dependent basophil histamine release was only obtained with sera containing therapy-induced allergen-specific IgG, but not with sera obtained before therapy or from placebo-treated patients. Moreover, patients with therapy-induced allergen-specific IgG antibodies showed a reduced induction of allergen-specific IgE responses during seasonal grass pollen exposure. Conclusion Successful immunotherapy with the MPL-adjuvanted grass pollen allergy vaccine is associated with the production of allergen-specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate-type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.	35	156	2003	11	10.1046/j.1365-2222.2003.01699.x	Allergy; Immunology
Domestic exposure to formaldehyde significantly increases the risk of asthma in young children. Concern has arisen in recent years about indoor air pollution as a risk factor for asthma. Formaldehyde exposure vas examined in relation to asthma among young children (between 6 months and 3 yrs old) in a population-based control study carried out in Perth, Western Australia, between 1997-1999. An association between exposure to formaldehyde and asthma in young children has been suggested. Cases (n=88), whose parents were recruited at Princess Margaret Hospital Accident and Emergency Dept (Perth, Western Australia), were children discharged with asthma as the primary diagnosis. Controls (n=104), who were children in the same age group without asthma diagnosed by a doctor, were identified from birth records through the Health Dept of Western Australia (Perth, Western Australia). Health outcomes for the children were studied using a respiratory questionnaire and skin-prick tests. Formaldehyde, average temperature and relative humidity were measured on two occasions, winter (July-September 1998) and summer (December 1998-March 1999) in the child's bedroom and in the living room. The study found seasonal differences in formaldehyde levels in the children's bedrooms and living rooms with significantly greater formaldehyde exposure during the summer period for case and control subjects. The generalised estimating equation model showed that children exposed to formaldehyde levels of greater than or equal to60 mug.m(-3) are at increased risk of having asthma. The results suggest that domestic exposure to formaldehyde increases the risk of childhood asthma.. asthma| children| formaldehyde| indoor air quality|volatile organic-compounds| longitudinal data-analysis| childhood| association| allergens| dioxide.	AUG-2002	asthma| children| formaldehyde| indoor air quality|volatile organic-compounds| longitudinal data-analysis| childhood| association| allergens| dioxide	Rumchev, KB; Spickett, JT; Bulsara, MK; Phillips, MR; Stick, SM	Domestic exposure to formaldehyde significantly increases the risk of asthma in young children		EUROPEAN RESPIRATORY JOURNAL	asthma; children; formaldehyde; indoor air quality	VOLATILE ORGANIC-COMPOUNDS; LONGITUDINAL DATA-ANALYSIS; CHILDHOOD; ASSOCIATION; ALLERGENS; DIOXIDE	Concern has arisen in recent years about indoor air pollution as a risk factor for asthma. Formaldehyde exposure vas examined in relation to asthma among young children (between 6 months and 3 yrs old) in a population-based control study carried out in Perth, Western Australia, between 1997-1999. An association between exposure to formaldehyde and asthma in young children has been suggested. Cases (n=88), whose parents were recruited at Princess Margaret Hospital Accident and Emergency Dept (Perth, Western Australia), were children discharged with asthma as the primary diagnosis. Controls (n=104), who were children in the same age group without asthma diagnosed by a doctor, were identified from birth records through the Health Dept of Western Australia (Perth, Western Australia). Health outcomes for the children were studied using a respiratory questionnaire and skin-prick tests. Formaldehyde, average temperature and relative humidity were measured on two occasions, winter (July-September 1998) and summer (December 1998-March 1999) in the child's bedroom and in the living room. The study found seasonal differences in formaldehyde levels in the children's bedrooms and living rooms with significantly greater formaldehyde exposure during the summer period for case and control subjects. The generalised estimating equation model showed that children exposed to formaldehyde levels of greater than or equal to60 mug.m(-3) are at increased risk of having asthma. The results suggest that domestic exposure to formaldehyde increases the risk of childhood asthma.	30	156	2002	6	10.1183/09031936.02.00245002	Respiratory System
Bacterial and fungal aerosol in indoor environment in Upper Silesia, Poland. The purpose of this study was to find the typical concentration levels of bacterial and fungal bioaerosol in healthy and moldy homes as well as in office rooms in Upper Silesia Industrial Zone. Airborne bacteria and fungi were collected using the 6-stage Andersen impactor inside and outside of buildings. It was found that the typical level of bacterial aerosol indoors is about 10(3) CFU m(-3) in horncs and 10(2) CFU m(-3) in offices, Only Micrococcus spp was present in all homes studied, constituting 36% of the bacterial genera. The second most common was Staphylococcus epidermidis, present in 76% of homes and constituting 14% of the total. The concentration of fungal aerosol in winter ranged from 10 to 102 CFU m-3 in healthy homes and from 10 to 103 CFU m-3 in homes with mold problems. In summer these values were elevated reaching 10(3) CFU m(-3) in healthy homes and 10(3)-10(4) CFU m-3 in moldy buildings. In healthy homes the relative concentration of observed species, including Penicillium, ranged from 3 to about 50% while in moldy homes the highest concentration of Penicillium accounted for 90% of the total fungi. However, the differences between viable fungal species as well as concentrations observed in moldy and healthy homes seem to be too small to be a reason of significantly higher risk for allergic asthma symptoms in any group of buildings. Comparison of the respirable fraction of airborne bacteria and Fungi with literature data suggests that the percentage of respirable fungi and bacteria is generally not dependent on the type of home, building material, geographical factors and particulate air pollution. (C) 2000 Elsevier Science Ltd. All rights reserved.. bioaerosol| bacteria| fungi| indoor air| mold problem|respiratory symptoms| mold problems| air-quality| homes| prevalence| katowice| damp| schoolchildren| bioaerosols| particles.	2000	bioaerosol| bacteria| fungi| indoor air| mold problem|respiratory symptoms| mold problems| air-quality| homes| prevalence| katowice| damp| schoolchildren| bioaerosols| particles	Pastuszka, JS; Paw, UKT; Lis, DO; Wlazlo, A; Ulfig, K	Bacterial and fungal aerosol in indoor environment in Upper Silesia, Poland		ATMOSPHERIC ENVIRONMENT	bioaerosol; bacteria; fungi; indoor air; mold problem	RESPIRATORY SYMPTOMS; MOLD PROBLEMS; AIR-QUALITY; HOMES; PREVALENCE; KATOWICE; DAMP; SCHOOLCHILDREN; BIOAEROSOLS; PARTICLES	The purpose of this study was to find the typical concentration levels of bacterial and fungal bioaerosol in healthy and moldy homes as well as in office rooms in Upper Silesia Industrial Zone. Airborne bacteria and fungi were collected using the 6-stage Andersen impactor inside and outside of buildings. It was found that the typical level of bacterial aerosol indoors is about 10(3) CFU m(-3) in horncs and 10(2) CFU m(-3) in offices, Only Micrococcus spp was present in all homes studied, constituting 36% of the bacterial genera. The second most common was Staphylococcus epidermidis, present in 76% of homes and constituting 14% of the total. The concentration of fungal aerosol in winter ranged from 10 to 102 CFU m-3 in healthy homes and from 10 to 103 CFU m-3 in homes with mold problems. In summer these values were elevated reaching 10(3) CFU m(-3) in healthy homes and 10(3)-10(4) CFU m-3 in moldy buildings. In healthy homes the relative concentration of observed species, including Penicillium, ranged from 3 to about 50% while in moldy homes the highest concentration of Penicillium accounted for 90% of the total fungi. However, the differences between viable fungal species as well as concentrations observed in moldy and healthy homes seem to be too small to be a reason of significantly higher risk for allergic asthma symptoms in any group of buildings. Comparison of the respirable fraction of airborne bacteria and Fungi with literature data suggests that the percentage of respirable fungi and bacteria is generally not dependent on the type of home, building material, geographical factors and particulate air pollution. (C) 2000 Elsevier Science Ltd. All rights reserved.	55	156	2000	10	10.1016/S1352-2310(99)00527-0	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Importance of Cytokines in Murine Allergic Airway Disease and Human Asthma. Asthma is a common, disabling inflammatory respiratory disease that has increased in frequency and severity in developed nations. We review studies of murine allergic airway disease (MAAD) and human asthma that evaluate the importance of Th2 cytokines, Th2 response-promoting cytokines, IL-17, and proinflammatory and anti-inflammatory cytokines in MAAD and human asthma. We discuss murine studies that directly stimulate airways with specific cytokines or delete, inactivate, neutralize, or block specific cytokines or their receptors, as well as controversial issues including the roles of IL-5, IL-17, and IL-13R alpha 2 in MAAD and IL-4R alpha expression by specific cell types. Studies of human asthmatic cytokine gene and protein expression, linkage of cytokine polymorphisms to asthma, cytokine responses to allergen stimulation, and clinical responses to cytokine antagonists are discussed as well. Results of these analyses establish the importance of specific cytokines in MAAD and human asthma and have therapeutic implications. The journal of Immunology, 2010, 184: 1663-1674.. necrosis-factor-alpha| il-5 messenger-rna| thymic stromal lymphopoietin| receptor antagonist gene| single-nucleotide polymorphism| dendritic cell maturation| colony-stimulating factor| childhood atopic asthma| dust-mite exposure| serum ige levels.	FEB 15-2010	necrosis-factor-alpha| il-5 messenger-rna| thymic stromal lymphopoietin| receptor antagonist gene| single-nucleotide polymorphism| dendritic cell maturation| colony-stimulating factor| childhood atopic asthma| dust-mite exposure| serum ige levels	Finkelman, FD; Hogan, SP; Hershey, GKK; Rothenberg, ME; Wills-Karp, M	Importance of Cytokines in Murine Allergic Airway Disease and Human Asthma		JOURNAL OF IMMUNOLOGY		NECROSIS-FACTOR-ALPHA; IL-5 MESSENGER-RNA; THYMIC STROMAL LYMPHOPOIETIN; RECEPTOR ANTAGONIST GENE; SINGLE-NUCLEOTIDE POLYMORPHISM; DENDRITIC CELL MATURATION; COLONY-STIMULATING FACTOR; CHILDHOOD ATOPIC ASTHMA; DUST-MITE EXPOSURE; SERUM IGE LEVELS	Asthma is a common, disabling inflammatory respiratory disease that has increased in frequency and severity in developed nations. We review studies of murine allergic airway disease (MAAD) and human asthma that evaluate the importance of Th2 cytokines, Th2 response-promoting cytokines, IL-17, and proinflammatory and anti-inflammatory cytokines in MAAD and human asthma. We discuss murine studies that directly stimulate airways with specific cytokines or delete, inactivate, neutralize, or block specific cytokines or their receptors, as well as controversial issues including the roles of IL-5, IL-17, and IL-13R alpha 2 in MAAD and IL-4R alpha expression by specific cell types. Studies of human asthmatic cytokine gene and protein expression, linkage of cytokine polymorphisms to asthma, cytokine responses to allergen stimulation, and clinical responses to cytokine antagonists are discussed as well. Results of these analyses establish the importance of specific cytokines in MAAD and human asthma and have therapeutic implications. The journal of Immunology, 2010, 184: 1663-1674.	264	155	2010	12	10.4049/jimmunol.0902185	Immunology
High diversity of fungi in air particulate matter. Fungal spores can account for large proportions of air particulate matter, and they may potentially influence the hydrological cycle and climate as nuclei for water droplets and ice crystals in clouds, fog, and precipitation. Moreover, some fungi are major pathogens and allergens. The diversity of airborne fungi is, however, not well-known. By DNA analysis we found pronounced differences in the relative abundance and seasonal cycles of various groups of fungi in coarse and fine particulate matter, with more plant pathogens in the coarse fraction and more human pathogens and allergens in the respirable fine particle fraction (<3 mu m). Moreover, the ratio of Basidiomycota to Ascomycota was found to be much higher than previously assumed, which might also apply to the biosphere.. atmospheric aerosol| bioaerosol| dna analysis| fungal spores|high-alpine air| environmental-samples| atmospheric processes| endophytic fungi| dna-polymerases| airborne fungi| aerosols| spores| urban| precipitation.	AUG 4-2009	atmospheric aerosol| bioaerosol| dna analysis| fungal spores|high-alpine air| environmental-samples| atmospheric processes| endophytic fungi| dna-polymerases| airborne fungi| aerosols| spores| urban| precipitation	Frohlich-Nowoisky, J; Pickersgill, DA; Despres, VR; Poschl, U	High diversity of fungi in air particulate matter		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	atmospheric aerosol; bioaerosol; DNA analysis; fungal spores	HIGH-ALPINE AIR; ENVIRONMENTAL-SAMPLES; ATMOSPHERIC PROCESSES; ENDOPHYTIC FUNGI; DNA-POLYMERASES; AIRBORNE FUNGI; AEROSOLS; SPORES; URBAN; PRECIPITATION	Fungal spores can account for large proportions of air particulate matter, and they may potentially influence the hydrological cycle and climate as nuclei for water droplets and ice crystals in clouds, fog, and precipitation. Moreover, some fungi are major pathogens and allergens. The diversity of airborne fungi is, however, not well-known. By DNA analysis we found pronounced differences in the relative abundance and seasonal cycles of various groups of fungi in coarse and fine particulate matter, with more plant pathogens in the coarse fraction and more human pathogens and allergens in the respirable fine particle fraction (<3 mu m). Moreover, the ratio of Basidiomycota to Ascomycota was found to be much higher than previously assumed, which might also apply to the biosphere.	62	155	2009	6	10.1073/pnas.0811003106	Science & Technology - Other Topics
Evidence based guidelines for the prevention, identification, and management of occupational asthma. Background: Occupational asthma is the most frequently reported work related respiratory disease in many countries. This work was commissioned by the British Occupational Health Research Foundation to assist the Health and Safety Executive in achieving its target of reducing the incidence of occupational asthma in Great Britain by 30% by 2010. Aim: The guidelines aim to improve the prevention, identification, and management of occupational asthma by providing evidence based recommendations on which future practice can be based. Methods: The literature was searched systematically using Medline and Embase for articles published in all languages up to the end of June 2004. Evidence based statements and recommendations were graded according to the Royal College of General Practitioner's star system and the revised Scottish Intercollegiate Guidelines Network grading system. Results: A total of 474 original studies were selected for appraisal from over 2500 abstracts. The systematic review produced 52 graded evidence statements and 22 recommendations based on 223 studies. Discussion: Evidence based guidelines have become benchmarks for practice in healthcare and the process used to prepare them is well established. This evidence review and its recommendations focus on interventions and outcomes to provide a robust approach to the prevention, identification, and management of occupational asthma, based on and using the best available medical evidence. The most important action to prevent cases of occupational asthma is to reduce exposure at source. Thereafter surveillance should be performed for the early identification of symptoms, including occupational rhinitis, with additional functional and immunological tests where appropriate. Effective management of workers suspected to have occupational asthma involves the identification and investigation of symptoms suggestive of asthma immediately they occur. Those workers who are confirmed to have occupational asthma should be advised to avoid further exposure completely and early in the course of their disease to offer the best chance of recovery.. peak expiratory flow| diisocyanate-induced asthma| laboratory-animal allergy| natural-rubber latex| isocyanate-induced asthma| work-related symptoms| health-care workers| exposure-response relationships| immunological lung-disease| crab-processing workers.	MAY-2005	peak expiratory flow| diisocyanate-induced asthma| laboratory-animal allergy| natural-rubber latex| isocyanate-induced asthma| work-related symptoms| health-care workers| exposure-response relationships| immunological lung-disease| crab-processing workers	Nicholson, PJ; Cullinan, P; Taylor, AJN; Burge, PS; Boyle, C	Evidence based guidelines for the prevention, identification, and management of occupational asthma		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		PEAK EXPIRATORY FLOW; DIISOCYANATE-INDUCED ASTHMA; LABORATORY-ANIMAL ALLERGY; NATURAL-RUBBER LATEX; ISOCYANATE-INDUCED ASTHMA; WORK-RELATED SYMPTOMS; HEALTH-CARE WORKERS; EXPOSURE-RESPONSE RELATIONSHIPS; IMMUNOLOGICAL LUNG-DISEASE; CRAB-PROCESSING WORKERS	Background: Occupational asthma is the most frequently reported work related respiratory disease in many countries. This work was commissioned by the British Occupational Health Research Foundation to assist the Health and Safety Executive in achieving its target of reducing the incidence of occupational asthma in Great Britain by 30% by 2010. Aim: The guidelines aim to improve the prevention, identification, and management of occupational asthma by providing evidence based recommendations on which future practice can be based. Methods: The literature was searched systematically using Medline and Embase for articles published in all languages up to the end of June 2004. Evidence based statements and recommendations were graded according to the Royal College of General Practitioner's star system and the revised Scottish Intercollegiate Guidelines Network grading system. Results: A total of 474 original studies were selected for appraisal from over 2500 abstracts. The systematic review produced 52 graded evidence statements and 22 recommendations based on 223 studies. Discussion: Evidence based guidelines have become benchmarks for practice in healthcare and the process used to prepare them is well established. This evidence review and its recommendations focus on interventions and outcomes to provide a robust approach to the prevention, identification, and management of occupational asthma, based on and using the best available medical evidence. The most important action to prevent cases of occupational asthma is to reduce exposure at source. Thereafter surveillance should be performed for the early identification of symptoms, including occupational rhinitis, with additional functional and immunological tests where appropriate. Effective management of workers suspected to have occupational asthma involves the identification and investigation of symptoms suggestive of asthma immediately they occur. Those workers who are confirmed to have occupational asthma should be advised to avoid further exposure completely and early in the course of their disease to offer the best chance of recovery.	230	155	2005	10	10.1136/oem.2004.016287	Public, Environmental & Occupational Health
Breast-feeding reduces the risk of asthma during the first 4 years of life. Background: The evidence for a preventive effect of breast-feeding on asthma and other allergic diseases in childhood is inconclusive. Objective: The aim of this study was to investigate the effect of breast-feeding on asthma and sensitization to airborne allergens among children up to 4 years of age. Methods: A birth cohort of 4089 children was followed. Exposure data were collected at 2 months and 1 year of age. The total dose of breast milk was estimated by combining periods of exclusive and partial breast-feeding. Outcomes data were collected at 1, 2, and 4 years of age. The response rate at 4 years was 90%, and 73% participated in a clinical investigation, including blood sampling for analysis of specific IgE and lung function testing. Children with onset of wheeze during lactation (n = 217) were excluded in some of the analyses to avoid disease-related modification of exposure. Results: Exclusive breast-feeding for 4 months or more reduced the risk of asthma at the age of 4 years (odds ratio [OR], 0.72; 95% CI, 0.53-0.97), irrespective of sensitization to common airborne allergens (P = .72). Excluding children with wheeze during lactation tended to strengthen the risk estimate (OR, 0.64; 95% CI, 0.46-0.88). A duration of 3 months or more of partial breast-feeding seemed to offer additional protection; exclusive breast-feeding for 3 to 4 months combined with partial breast-feeding for 3 months or more resulted in an OR of 0.44 (95% CI, 0.21-0.87). The effects tended to be stronger in children without heredity for allergy (P interaction = .36). Conclusion: Breast-feeding reduces the risk of asthma during the first 4 years of life.. allergy| asthma| sensitization| breast-fieeding| children| primary prevention| prospective studies| bamse|birth cohort| atopic disease| nonallergic mothers| follow-up| children| childhood| prevalence| milk| association| controversy.	OCT-2004	allergy| asthma| sensitization| breast-fieeding| children| primary prevention| prospective studies| bamse|birth cohort| atopic disease| nonallergic mothers| follow-up| children| childhood| prevalence| milk| association| controversy	Kull, I; Almqvist, C; Lilja, G; Pershagen, G; Wickman, M	Breast-feeding reduces the risk of asthma during the first 4 years of life		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; asthma; sensitization; breast-fieeding; children; primary prevention; prospective studies; BAMSE	BIRTH COHORT; ATOPIC DISEASE; NONALLERGIC MOTHERS; FOLLOW-UP; CHILDREN; CHILDHOOD; PREVALENCE; MILK; ASSOCIATION; CONTROVERSY	Background: The evidence for a preventive effect of breast-feeding on asthma and other allergic diseases in childhood is inconclusive. Objective: The aim of this study was to investigate the effect of breast-feeding on asthma and sensitization to airborne allergens among children up to 4 years of age. Methods: A birth cohort of 4089 children was followed. Exposure data were collected at 2 months and 1 year of age. The total dose of breast milk was estimated by combining periods of exclusive and partial breast-feeding. Outcomes data were collected at 1, 2, and 4 years of age. The response rate at 4 years was 90%, and 73% participated in a clinical investigation, including blood sampling for analysis of specific IgE and lung function testing. Children with onset of wheeze during lactation (n = 217) were excluded in some of the analyses to avoid disease-related modification of exposure. Results: Exclusive breast-feeding for 4 months or more reduced the risk of asthma at the age of 4 years (odds ratio [OR], 0.72; 95% CI, 0.53-0.97), irrespective of sensitization to common airborne allergens (P = .72). Excluding children with wheeze during lactation tended to strengthen the risk estimate (OR, 0.64; 95% CI, 0.46-0.88). A duration of 3 months or more of partial breast-feeding seemed to offer additional protection; exclusive breast-feeding for 3 to 4 months combined with partial breast-feeding for 3 months or more resulted in an OR of 0.44 (95% CI, 0.21-0.87). The effects tended to be stronger in children without heredity for allergy (P interaction = .36). Conclusion: Breast-feeding reduces the risk of asthma during the first 4 years of life.	31	155	2004	6	10.1016/j.jaci.2004.07.036	Allergy; Immunology
Inflammation, infection, and pulmonary function in infants and young children with cystic fibrosis. Our aim was to study the effect of lower airway infection on clinical parameters, pulmonary function tests, and inflammation in clinically stable infants and young children with cystic fibrosis (CF). To accomplish this goal, a prospective cohort of screened CF patients under 4 years of age were studied, using elective anesthesia and intubation for: passive respiratory mechanics (single breath occlusion passive deflation) and lung volumes (nitrogen washout), under neuromuscular blockade; and bronchoalveolar lavage (BAL) of 3 main bronchi for cytology, cytokine interleukin (IL)-8, and quantitative microbiology. There were 22 children studied, with a mean age of 23.2 months (6.7-44 months). A greater relative risk of lower airway pathogens was associated with prior respiratory admission (3.60, 95% confidence interval [CI] 2.87-4.51), history of asthma (1.75, 95% Cl 1.52-2.03), and chronic symptoms (1.50, 95% Cl 1.23-1.83), especially wheeze (1.88, 95% Cl 1.61-2.19). Lower respiratory pathogens (greater than or equal to 10 cfu/ml BAL) were found in 14 out of 22, and greater than 10(5) cfu/ml in 8 out of 22 subjects. The level of pathogens in BAL (log(10) cfu/ml) explained 78% of the variability in percent neutrophils and 34% of the variability in IL-8 levels. Pathogen level also correlated with pulmonary function tests of specific respiratory system compliance (r -0.49, p = 0.02) and functional residual capacity over total lung capacity (r 0.49, p = 0.03). We conclude that the presence of pathogens in the lower airways correlated with levels of inflammation, respiratory system compliance, and degree of air trapping.. cystic fibrosis| infants| respiratory function tests|1st 5 years| bronchoalveolar lavage| pseudomonas-aeruginosa| respiratory mechanics| airway inflammation| ventilated infants| lung inflammation| residual capacity| washout| responsiveness.	APR 1-2002	cystic fibrosis| infants| respiratory function tests|1st 5 years| bronchoalveolar lavage| pseudomonas-aeruginosa| respiratory mechanics| airway inflammation| ventilated infants| lung inflammation| residual capacity| washout| responsiveness	Dakin, CJ; Numa, AH; Wang, H; Morton, JR; Vertzyas, CC; Henry, RL	Inflammation, infection, and pulmonary function in infants and young children with cystic fibrosis		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	cystic fibrosis; infants; respiratory function tests	1ST 5 YEARS; BRONCHOALVEOLAR LAVAGE; PSEUDOMONAS-AERUGINOSA; RESPIRATORY MECHANICS; AIRWAY INFLAMMATION; VENTILATED INFANTS; LUNG INFLAMMATION; RESIDUAL CAPACITY; WASHOUT; RESPONSIVENESS	Our aim was to study the effect of lower airway infection on clinical parameters, pulmonary function tests, and inflammation in clinically stable infants and young children with cystic fibrosis (CF). To accomplish this goal, a prospective cohort of screened CF patients under 4 years of age were studied, using elective anesthesia and intubation for: passive respiratory mechanics (single breath occlusion passive deflation) and lung volumes (nitrogen washout), under neuromuscular blockade; and bronchoalveolar lavage (BAL) of 3 main bronchi for cytology, cytokine interleukin (IL)-8, and quantitative microbiology. There were 22 children studied, with a mean age of 23.2 months (6.7-44 months). A greater relative risk of lower airway pathogens was associated with prior respiratory admission (3.60, 95% confidence interval [CI] 2.87-4.51), history of asthma (1.75, 95% Cl 1.52-2.03), and chronic symptoms (1.50, 95% Cl 1.23-1.83), especially wheeze (1.88, 95% Cl 1.61-2.19). Lower respiratory pathogens (greater than or equal to 10 cfu/ml BAL) were found in 14 out of 22, and greater than 10(5) cfu/ml in 8 out of 22 subjects. The level of pathogens in BAL (log(10) cfu/ml) explained 78% of the variability in percent neutrophils and 34% of the variability in IL-8 levels. Pathogen level also correlated with pulmonary function tests of specific respiratory system compliance (r -0.49, p = 0.02) and functional residual capacity over total lung capacity (r 0.49, p = 0.03). We conclude that the presence of pathogens in the lower airways correlated with levels of inflammation, respiratory system compliance, and degree of air trapping.	52	155	2002	7	10.1164/rccm.2010139	General & Internal Medicine; Respiratory System
Early exposure to infections and antibiotics and the incidence of allergic disease: A birth cohort study with the West Midlands General Practice Research Database. Background: It has been suggested that the rise in prevalence of allergic disease in westernized countries is due in part to a decrease in exposure to infections and an increase in the use of antibiotics early in life. Objective: The purpose of this investigation was to quantify the relationships between (1) exposure to personal infections, infections in siblings, and use of antibiotics in early life and (2) the incidence of allergic disease. Methods: Using the West Midlands section of the UK General Practice Research Database, we established a historical birth cohort of children (N = 29,238). For each child, we identified all personal infections and infections in siblings and determined the use of antibiotics in early life; we also noted incident diagnoses of asthma, eczema, and hay fever. The data were analyzed through use of Cox regression. Results: There was no clear protective effect of exposure to either personal infections or infections in siblings with respect to the incidence of allergic disease. Antibiotic exposure was associated with an increased risk of developing allergic disease in a dose-related manner: having 4 or more courses of antibiotics in the first year of life was associated with an increased incidence of asthma (hazard ratio [HR), 3.13; 95% CI, 2.75-3.57), eczema (HR, 1.48; 95% CI, 1.31-1.68), and hay fever (HR, 2.12; 95% CI, 1.68-2.66). However, adjusting for consulting behavior reduced these effects (adjusted HR [95% CI]: asthma, 1.99 [1.72-2.31]; eczema, 1.01 [0.88-1.17]; hay fever, 1.14 [0.88-1.47]). Conclusions: We found no evidence that exposure to infections reduced the incidence of allergic disease, and infections did not explain the previous findings of a strong birth order effect in this cohort. The use of antibiotics might be associated with early diagnoses of allergic disease.. asthma| eczema| hay fever| infections| siblings| antibiotics| cohort|respiratory syncytial virus| hay-fever| atopic disorder| guinea-bissau| family-size| asthma| children| measles| risk| prevalence.	JAN-2002	asthma| eczema| hay fever| infections| siblings| antibiotics| cohort|respiratory syncytial virus| hay-fever| atopic disorder| guinea-bissau| family-size| asthma| children| measles| risk| prevalence	McKeever, TM; Lewis, SA; Smith, C; Collins, J; Heatlie, H; Frischer, M; Hubbard, R	Early exposure to infections and antibiotics and the incidence of allergic disease: A birth cohort study with the West Midlands General Practice Research Database		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; eczema; hay fever; infections; siblings; antibiotics; cohort	RESPIRATORY SYNCYTIAL VIRUS; HAY-FEVER; ATOPIC DISORDER; GUINEA-BISSAU; FAMILY-SIZE; ASTHMA; CHILDREN; MEASLES; RISK; PREVALENCE	Background: It has been suggested that the rise in prevalence of allergic disease in westernized countries is due in part to a decrease in exposure to infections and an increase in the use of antibiotics early in life. Objective: The purpose of this investigation was to quantify the relationships between (1) exposure to personal infections, infections in siblings, and use of antibiotics in early life and (2) the incidence of allergic disease. Methods: Using the West Midlands section of the UK General Practice Research Database, we established a historical birth cohort of children (N = 29,238). For each child, we identified all personal infections and infections in siblings and determined the use of antibiotics in early life; we also noted incident diagnoses of asthma, eczema, and hay fever. The data were analyzed through use of Cox regression. Results: There was no clear protective effect of exposure to either personal infections or infections in siblings with respect to the incidence of allergic disease. Antibiotic exposure was associated with an increased risk of developing allergic disease in a dose-related manner: having 4 or more courses of antibiotics in the first year of life was associated with an increased incidence of asthma (hazard ratio [HR), 3.13; 95% CI, 2.75-3.57), eczema (HR, 1.48; 95% CI, 1.31-1.68), and hay fever (HR, 2.12; 95% CI, 1.68-2.66). However, adjusting for consulting behavior reduced these effects (adjusted HR [95% CI]: asthma, 1.99 [1.72-2.31]; eczema, 1.01 [0.88-1.17]; hay fever, 1.14 [0.88-1.47]). Conclusions: We found no evidence that exposure to infections reduced the incidence of allergic disease, and infections did not explain the previous findings of a strong birth order effect in this cohort. The use of antibiotics might be associated with early diagnoses of allergic disease.	25	155	2002	8	10.1067/mai.2002.121016	Allergy; Immunology
Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section. important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response. Design The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months. Results Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood. Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.. intestinal microbiota| immune-responses| fecal samples| t-cells| bacteria| allergy| asthma| children| eczema| mode.	APR-2014	intestinal microbiota| immune-responses| fecal samples| t-cells| bacteria| allergy| asthma| children| eczema| mode	Jakobsson, HE; Abrahamsson, TR; Jenmalm, MC; Harris, K; Quince, C; Jernberg, C; Bjorksten, B; Engstrand, L; Andersson, AF	Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section		GUT		INTESTINAL MICROBIOTA; IMMUNE-RESPONSES; FECAL SAMPLES; T-CELLS; BACTERIA; ALLERGY; ASTHMA; CHILDREN; ECZEMA; MODE	important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response. Design The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months. Results Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood. Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.	53	154	2014	8	10.1136/gutjnl-2012-303249	Gastroenterology & Hepatology
Ventilation rates and health: multidisciplinary review of the scientific literature. P>The scientific literature through 2005 on the effects of ventilation rates on health in indoor environments has been reviewed by a multidisciplinary group. The group judged 27 papers published in peer-reviewed scientific journals as providing sufficient information on both ventilation rates and health effects to inform the relationship. Consistency was found across multiple investigations and different epidemiologic designs for different populations. Multiple health endpoints show similar relationships with ventilation rate. There is biological plausibility for an association of health outcomes with ventilation rates, although the literature does not provide clear evidence on particular agent(s) for the effects. Higher ventilation rates in offices, up to about 25 l/s per person, are associated with reduced prevalence of sick building syndrome (SBS) symptoms. The limited available data suggest that inflammation, respiratory infections, asthma symptoms and short-term sick leave increase with lower ventilation rates. Home ventilation rates above 0.5 air changes per hour (h-1) have been associated with a reduced risk of allergic manifestations among children in a Nordic climate. The need remains for more studies of the relationship between ventilation rates and health, especially in diverse climates, in locations with polluted outdoor air and in buildings other than offices. Practical Implications Ventilation with outdoor air plays an important role influencing human exposures to indoor pollutants. This review and assessment indicates that increasing ventilation rates above currently adopted standards and guidelines should result in reduced prevalence of negative health outcomes. Building operators and designers should avoid low ventilation rates unless alternative effective measures, such as source control or air cleaning, are employed to limit indoor pollutant levels.. outdoor air supply rate| indoor air quality| offices| schools| homes|sick-building-syndrome| indoor air-quality| syndrome sbs symptoms| house-dust mites| office buildings| co2 concentrations| exchange-rate| respiratory-diseases| carbon-dioxide| young-children.	JUN-2011	outdoor air supply rate| indoor air quality| offices| schools| homes|sick-building-syndrome| indoor air-quality| syndrome sbs symptoms| house-dust mites| office buildings| co2 concentrations| exchange-rate| respiratory-diseases| carbon-dioxide| young-children	Sundell, J; Levin, H; Nazaroff, WW; Cain, WS; Fisk, WJ; Grimsrud, DT; Gyntelberg, F; Li, Y; Persily, AK; Pickering, AC; Samet, JM; Spengler, JD; Taylor, ST; Weschler, CJ	Ventilation rates and health: multidisciplinary review of the scientific literature		INDOOR AIR	Outdoor air supply rate; Indoor air quality; Offices; Schools; Homes	SICK-BUILDING-SYNDROME; INDOOR AIR-QUALITY; SYNDROME SBS SYMPTOMS; HOUSE-DUST MITES; OFFICE BUILDINGS; CO2 CONCENTRATIONS; EXCHANGE-RATE; RESPIRATORY-DISEASES; CARBON-DIOXIDE; YOUNG-CHILDREN	P>The scientific literature through 2005 on the effects of ventilation rates on health in indoor environments has been reviewed by a multidisciplinary group. The group judged 27 papers published in peer-reviewed scientific journals as providing sufficient information on both ventilation rates and health effects to inform the relationship. Consistency was found across multiple investigations and different epidemiologic designs for different populations. Multiple health endpoints show similar relationships with ventilation rate. There is biological plausibility for an association of health outcomes with ventilation rates, although the literature does not provide clear evidence on particular agent(s) for the effects. Higher ventilation rates in offices, up to about 25 l/s per person, are associated with reduced prevalence of sick building syndrome (SBS) symptoms. The limited available data suggest that inflammation, respiratory infections, asthma symptoms and short-term sick leave increase with lower ventilation rates. Home ventilation rates above 0.5 air changes per hour (h-1) have been associated with a reduced risk of allergic manifestations among children in a Nordic climate. The need remains for more studies of the relationship between ventilation rates and health, especially in diverse climates, in locations with polluted outdoor air and in buildings other than offices. Practical Implications Ventilation with outdoor air plays an important role influencing human exposures to indoor pollutants. This review and assessment indicates that increasing ventilation rates above currently adopted standards and guidelines should result in reduced prevalence of negative health outcomes. Building operators and designers should avoid low ventilation rates unless alternative effective measures, such as source control or air cleaning, are employed to limit indoor pollutant levels.	61	154	2011	14	10.1111/j.1600-0668.2010.00703.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel. Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways. Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 mum (PM10) 108 mug(.)m(-3)) and lung function and airway inflammation were assessed. Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin-8 (IL-8) protein in lavage fluid, increased IL-8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their preexisting eosinophilic airway inflammation. Epithelial staining for the cytokine IL-10 was increased after DE in the asthmatic group. Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 mum at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses.. airway inflammation| asthma| cytokines| diesel| pollution|exhaust particles| pollution| interleukin-10| cells.	JAN-2004	airway inflammation| asthma| cytokines| diesel| pollution|exhaust particles| pollution| interleukin-10| cells	Stenfors, N; Nordenhall, C; Salvi, SS; Mudway, I; Soderberg, M; Blomberg, A; Helleday, R; Levin, JO; Holgate, ST; Kelly, FJ; Frew, AJ; Sandstrom, T	Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel		EUROPEAN RESPIRATORY JOURNAL	airway inflammation; asthma; cytokines; diesel; pollution	EXHAUST PARTICLES; POLLUTION; INTERLEUKIN-10; CELLS	Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways. Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 mum (PM10) 108 mug(.)m(-3)) and lung function and airway inflammation were assessed. Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin-8 (IL-8) protein in lavage fluid, increased IL-8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their preexisting eosinophilic airway inflammation. Epithelial staining for the cytokine IL-10 was increased after DE in the asthmatic group. Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 mum at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses.	20	154	2004	5	10.1183/09031936.03.00004603	Respiratory System
Antacid medication inhibits digestion of dietary proteins and causes food allergy: A fish allergy model in Balb/c mice. Background: Digestible proteins were supposed to be irrelevant for oral sensitization and induction of food allergy. Approximately 10% of the adult population uses antacids for the treatment of dyspeptic disorders, drugs that hinder peptic digestion. In these patients, proteins that are normally degradable might act as food allergens. Objective: We aimed to study the influence of antacid intake on the allergenicity of dietary proteins, taking sturgeon caviar and parvalbumin, the major fish allergen, as examples. Methods: Caviar proteins and recombinant parvalbumin from carp, rCyp c 1, were applied for intragastric feedings with or without the antacids sucralfate, ranitidine or omeprazole, using a Balb/c mouse model. Results: Both caviar proteins and parvalbumin were rapidly degraded in an in vitro digestion assay at pH 2.0, but not at pH 5.0, imitating the effect of antacids. The groups fed with caviar in combination with ranitidine hydrochloride intramuscularly or sucralfate orally had significant levels of caviar-specific IgE antibodies (P < .01), T-cell reactivity, and elevated counts of gastrointestinal eosinophils and mast cells. Food allergy in these groups was further evidenced by oral provocation tests and positive immediate-type skin reactivity. In contrast, feedings with caviar alone led to antigen-specific T-cell tolerance. None of the groups showed immune reactivity against the daily mouse diet. As a proof of the principle, feeding mice with parvalbumin in combination with ranitidine or omeprazole intramuscularly induced allergen-specific IgE antibodies (P < .05). Conclusions: When antacid medication impairs the gastric digestion, IgE synthesis toward novel dietary proteins is promoted, leading to food allergy.. food allergy| caviar| parvalbumin| ige| nutrition| antacids| digestion| animal model|peanut| hypersensitivity| digestibility| epidemiology| intolerance| prevalence| population| responses| epitopes| exposure.	SEP-2003	food allergy| caviar| parvalbumin| ige| nutrition| antacids| digestion| animal model|peanut| hypersensitivity| digestibility| epidemiology| intolerance| prevalence| population| responses| epitopes| exposure	Untersmayr, E; Scholl, I; Swoboda, I; Beil, WJ; Forster-Waldl, E; Walter, F; Riemer, A; Kraml, G; Kinaciyan, T; Spitzauer, S; Boltz-Nitulescu, G; Scheiner, O; Jensen-Jarolim, E	Antacid medication inhibits digestion of dietary proteins and causes food allergy: A fish allergy model in Balb/c mice		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	food allergy; caviar; parvalbumin; IgE; nutrition; antacids; digestion; animal model	PEANUT; HYPERSENSITIVITY; DIGESTIBILITY; EPIDEMIOLOGY; INTOLERANCE; PREVALENCE; POPULATION; RESPONSES; EPITOPES; EXPOSURE	Background: Digestible proteins were supposed to be irrelevant for oral sensitization and induction of food allergy. Approximately 10% of the adult population uses antacids for the treatment of dyspeptic disorders, drugs that hinder peptic digestion. In these patients, proteins that are normally degradable might act as food allergens. Objective: We aimed to study the influence of antacid intake on the allergenicity of dietary proteins, taking sturgeon caviar and parvalbumin, the major fish allergen, as examples. Methods: Caviar proteins and recombinant parvalbumin from carp, rCyp c 1, were applied for intragastric feedings with or without the antacids sucralfate, ranitidine or omeprazole, using a Balb/c mouse model. Results: Both caviar proteins and parvalbumin were rapidly degraded in an in vitro digestion assay at pH 2.0, but not at pH 5.0, imitating the effect of antacids. The groups fed with caviar in combination with ranitidine hydrochloride intramuscularly or sucralfate orally had significant levels of caviar-specific IgE antibodies (P < .01), T-cell reactivity, and elevated counts of gastrointestinal eosinophils and mast cells. Food allergy in these groups was further evidenced by oral provocation tests and positive immediate-type skin reactivity. In contrast, feedings with caviar alone led to antigen-specific T-cell tolerance. None of the groups showed immune reactivity against the daily mouse diet. As a proof of the principle, feeding mice with parvalbumin in combination with ranitidine or omeprazole intramuscularly induced allergen-specific IgE antibodies (P < .05). Conclusions: When antacid medication impairs the gastric digestion, IgE synthesis toward novel dietary proteins is promoted, leading to food allergy.	38	154	2003	8	10.1016/mai.2003.1681	Allergy; Immunology
Exposure to endotoxin decreases the risk of atopic eczema in infancy: A cohort study. Background: Previous studies have shown a protective effect of early exposure to cats and dogs on the development of atopic eczema, asthma, allergic rhinitis, and atopic sensitization in later life. In particular, a higher microbial exposure to endotoxin in early childhood might contribute to this effect. Objective: We examined the associations between bacterial endotoxin in house dust and atopic eczema, infections, and wheezing during the first year of life in an ongoing birth cohort study (LISA). Methods: Data of 1884 term and normal-weight neonates with complete information on exposure to biocontaminants and confounding variables were analyzed. House dust from the mothers' and the children's mattresses was sampled 3 months after birth. Endotoxin content was quantified by using a chromogenic kinetic limulus amoebocyte lysate test. Results: During the first 6 months of life, the risk of atopic eczema was significantly decreased by endotoxin exposure in dust from mothers' mattresses in the fifth quintile (odds ratio [OR], 0.50; 95% CI, 0.28-0.88), whereas the risk was increased for respiratory infections (OR, 1.69; 95% CI, 1.25-2.28) and cough with respiratory infection, bronchitis, or both (OR, 1.73; 95% CI, 1.28-2.33). The risk of wheezing was also significantly increased during the first 6 months of life (OR, 2.37; 95% CI, 1.40-4.03). For the entire first year of life, these associations attenuated, except for the risk of wheezing, which remained significant (OR, 1.60; 95% CI, 1.10-2.30). Conclusion: Our findings support the hygiene hypothesis that exposure to high concentrations of endotoxin very early in life might protect against the development of atopic eczema within the first 6 months of life, along with an increased prevalence of nonspecific respiratory diseases.. endotoxin| house dust| atopic eczema| infections| wheezing| infancy|house-dust| hay-fever| allergic sensitization| asthma| children| dermatitis| childhood| environment| community| symptoms.	NOV-2001	endotoxin| house dust| atopic eczema| infections| wheezing| infancy|house-dust| hay-fever| allergic sensitization| asthma| children| dermatitis| childhood| environment| community| symptoms	Gehring, U; Bolte, G; Borte, M; Bischof, W; Fahlbusch, B; Wichmann, HE; Heinrich, J	Exposure to endotoxin decreases the risk of atopic eczema in infancy: A cohort study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	endotoxin; house dust; atopic eczema; infections; wheezing; infancy	HOUSE-DUST; HAY-FEVER; ALLERGIC SENSITIZATION; ASTHMA; CHILDREN; DERMATITIS; CHILDHOOD; ENVIRONMENT; COMMUNITY; SYMPTOMS	Background: Previous studies have shown a protective effect of early exposure to cats and dogs on the development of atopic eczema, asthma, allergic rhinitis, and atopic sensitization in later life. In particular, a higher microbial exposure to endotoxin in early childhood might contribute to this effect. Objective: We examined the associations between bacterial endotoxin in house dust and atopic eczema, infections, and wheezing during the first year of life in an ongoing birth cohort study (LISA). Methods: Data of 1884 term and normal-weight neonates with complete information on exposure to biocontaminants and confounding variables were analyzed. House dust from the mothers' and the children's mattresses was sampled 3 months after birth. Endotoxin content was quantified by using a chromogenic kinetic limulus amoebocyte lysate test. Results: During the first 6 months of life, the risk of atopic eczema was significantly decreased by endotoxin exposure in dust from mothers' mattresses in the fifth quintile (odds ratio [OR], 0.50; 95% CI, 0.28-0.88), whereas the risk was increased for respiratory infections (OR, 1.69; 95% CI, 1.25-2.28) and cough with respiratory infection, bronchitis, or both (OR, 1.73; 95% CI, 1.28-2.33). The risk of wheezing was also significantly increased during the first 6 months of life (OR, 2.37; 95% CI, 1.40-4.03). For the entire first year of life, these associations attenuated, except for the risk of wheezing, which remained significant (OR, 1.60; 95% CI, 1.10-2.30). Conclusion: Our findings support the hygiene hypothesis that exposure to high concentrations of endotoxin very early in life might protect against the development of atopic eczema within the first 6 months of life, along with an increased prevalence of nonspecific respiratory diseases.	36	154	2001	8	10.1067/mai.2001.119026	Allergy; Immunology
Environmental epigenetics and asthma - Current concepts and call for studies. Recent studies suggest that epigenetic regulation (heritable changes in gene expression that occur in the absence of alterations in DNA sequences) may in part mediate the complex gene-by-environment interactions that can lead to asthma. The variable natural history of asthma (i.e., incidence and remission of symptoms) may be a result of epigenetic changes, such as DNA methylation, covalent histone modifications, microRNA changes, and chromatin alterations, after early or later environmental exposures. Findings from multiple epidemiologic and experimental studies indicate that asthma risk may be modified by epigenetic regulation. One study suggested that the transmission of asthma risk may occur across multiple generations. Experimental studies provide substantial in vitro data indicating that DNA methylation of genes critical to T-helper cell differentiation may induce polarization toward or away from an allergic phenotype. Despite this initial progress, fundamental questions remain that need to be addressed by well-designed research studies. Data generated from controlled experiments using in vivo models and/or clinical specimens collected after environmental exposure monitoring are limited. Importantly, cohort-driven epigenetic research has the potential to address key questions, such as those concerning the influence of timing of exposure, dose of exposure, diet, and ethnicity on susceptibility to asthma development. There is immense promise that the study of environmental epigenetics will help us understand a theoretically preventable environmental disease.. epigenetics| asthma| dna methylation| gene-environment interactions|school-age-children| low-birth-weight| serum ige levels| ifn-gamma gene| childhood asthma| lung-function| tobacco-smoke| allergic disease| maternal smoking| dna methylation.	MAR 15-2008	epigenetics| asthma| dna methylation| gene-environment interactions|school-age-children| low-birth-weight| serum ige levels| ifn-gamma gene| childhood asthma| lung-function| tobacco-smoke| allergic disease| maternal smoking| dna methylation	Miller, RL; Ho, SM	Environmental epigenetics and asthma - Current concepts and call for studies		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	epigenetics; asthma; DNA methylation; gene-environment interactions	SCHOOL-AGE-CHILDREN; LOW-BIRTH-WEIGHT; SERUM IGE LEVELS; IFN-GAMMA GENE; CHILDHOOD ASTHMA; LUNG-FUNCTION; TOBACCO-SMOKE; ALLERGIC DISEASE; MATERNAL SMOKING; DNA METHYLATION	Recent studies suggest that epigenetic regulation (heritable changes in gene expression that occur in the absence of alterations in DNA sequences) may in part mediate the complex gene-by-environment interactions that can lead to asthma. The variable natural history of asthma (i.e., incidence and remission of symptoms) may be a result of epigenetic changes, such as DNA methylation, covalent histone modifications, microRNA changes, and chromatin alterations, after early or later environmental exposures. Findings from multiple epidemiologic and experimental studies indicate that asthma risk may be modified by epigenetic regulation. One study suggested that the transmission of asthma risk may occur across multiple generations. Experimental studies provide substantial in vitro data indicating that DNA methylation of genes critical to T-helper cell differentiation may induce polarization toward or away from an allergic phenotype. Despite this initial progress, fundamental questions remain that need to be addressed by well-designed research studies. Data generated from controlled experiments using in vivo models and/or clinical specimens collected after environmental exposure monitoring are limited. Importantly, cohort-driven epigenetic research has the potential to address key questions, such as those concerning the influence of timing of exposure, dose of exposure, diet, and ethnicity on susceptibility to asthma development. There is immense promise that the study of environmental epigenetics will help us understand a theoretically preventable environmental disease.	91	153	2008	7	10.1164/rccm.200710-1511PP	General & Internal Medicine; Respiratory System
Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children. Background A link between exposure to the air pollutant nitrogen dioxide (NO2) and respiratory disease has been suggested. Viral infections are the major cause of asthma exacerbations. We aimed to assess whether there is a relation between NO2 exposure and the severity of asthma exacerbations caused by proven respiratory viral infections in children. Methods A cohort of 114 asthmatic children aged between 8 and 11 years recorded daily upper and lower respiratory-tract symptoms, peak expiratory flow (PEF), and measured personal NO2 exposures every week for up to 13 months. We took nasal aspirates during reported episodes of upper respiratory-tract illness and tested for infection by common respiratory viruses and atypical bacteria with RT-PCR assays. We used generalised estimating equations to assess the relation between low (<7.5 &mu;g/m(3) medium (7.5-14 &mu;g/m(3)), and high (>14 mug/m(3)) tertiles of NO2 exposure in the week before or after upper respiratory-tract infection and the severity of asthma exacerbation in the week after the start of an infection. Findings One or more viruses were detected in 78% of reported infection episodes, and the medians of NO2 exposure were 5 (IQR 3.6-6.3), 10 (8.7-12.0), and 21 mug/m(3) (16.8-42.9) for low, medium, and high tertiles, respectively. There were significant increases in the severity of lower respiratory-tract symptom scores across the three tertiles (0.6 for all viruses [p=0.05] and >2 for respiratory syncytial virus [p=0.01]) and a reduction in PEF of more than 12 L/min for picornavirus (p=0.04) for high compared with low NO2 exposure before the start of the virus-induced exacerbation. Interpretation High exposure to NO2 in the week before the start of a respiratory viral infection, and at levels within current air quality standards, is associated with an increase in the severity of a resulting asthma exacerbation.. respiratory symptoms| air-pollution| risk-factors| in-vitro| association| infection| cooking| adults| cells| gas.	JUN 7-2003	respiratory symptoms| air-pollution| risk-factors| in-vitro| association| infection| cooking| adults| cells| gas	Chauhan, AJ; Inskip, HM; Linaker, CH; Smith, S; Schreiber, J; Johnston, SL; Holgate, ST	Personal exposure to nitrogen dioxide (NO2) and the severity of virus-induced asthma in children		LANCET		RESPIRATORY SYMPTOMS; AIR-POLLUTION; RISK-FACTORS; IN-VITRO; ASSOCIATION; INFECTION; COOKING; ADULTS; CELLS; GAS	Background A link between exposure to the air pollutant nitrogen dioxide (NO2) and respiratory disease has been suggested. Viral infections are the major cause of asthma exacerbations. We aimed to assess whether there is a relation between NO2 exposure and the severity of asthma exacerbations caused by proven respiratory viral infections in children. Methods A cohort of 114 asthmatic children aged between 8 and 11 years recorded daily upper and lower respiratory-tract symptoms, peak expiratory flow (PEF), and measured personal NO2 exposures every week for up to 13 months. We took nasal aspirates during reported episodes of upper respiratory-tract illness and tested for infection by common respiratory viruses and atypical bacteria with RT-PCR assays. We used generalised estimating equations to assess the relation between low (<7.5 &mu;g/m(3) medium (7.5-14 &mu;g/m(3)), and high (>14 mug/m(3)) tertiles of NO2 exposure in the week before or after upper respiratory-tract infection and the severity of asthma exacerbation in the week after the start of an infection. Findings One or more viruses were detected in 78% of reported infection episodes, and the medians of NO2 exposure were 5 (IQR 3.6-6.3), 10 (8.7-12.0), and 21 mug/m(3) (16.8-42.9) for low, medium, and high tertiles, respectively. There were significant increases in the severity of lower respiratory-tract symptom scores across the three tertiles (0.6 for all viruses [p=0.05] and >2 for respiratory syncytial virus [p=0.01]) and a reduction in PEF of more than 12 L/min for picornavirus (p=0.04) for high compared with low NO2 exposure before the start of the virus-induced exacerbation. Interpretation High exposure to NO2 in the week before the start of a respiratory viral infection, and at levels within current air quality standards, is associated with an increase in the severity of a resulting asthma exacerbation.	35	153	2003	6	10.1016/S0140-6736(03)13582-9	General & Internal Medicine
Airway and tissue mechanics in a murine model of asthma: alveolar capsule vs. forced oscillations. To better address the functional consequences of inflammation on bronchial responsiveness, we studied two groups of BALB/c mice: a nonimmunized control group (n = 8) and a group immunized and challenged with inhaled ovalbumin (n = 8). An alveolar capsule (AC) measured airway resistance (Raw(AC)) and lung elastance (EL). A forced oscillation (FO) technique independently estimated airway resistance (RawFO) and a parameter H-ti related to tissue elastance. Ovalbumin-immunized and -challenged mice had increased numbers of eosinophils in bronchoalveolar lavage and increased responsiveness to methacholine (MCh). Corresponding parameters from the AC and FO techniques were correlated: RawAC vs. RawFO (r = 0.76) and EL vs. H-ti (r = 0.88, P < 0.0001 in all cases). AC and FO techniques showed significant increases in tissue elastance in response to MCh but no significant increases in airway resistance. These results demonstrated that the AC and FO techniques yield essentially equivalent results in mice, even when the lung is inhomogeneous, and that the bronchoconstrictive responses to MCh and inflammation in mice are predominantly located in the lung periphery.. airway resistance| tissue elastance| lung impedance| antigen challenge| inflammation|respiratory system mechanics| induced constriction| lung-mechanics| dry air| rats| bronchoconstriction| histamine| impedance| pressure| behavior.	JUL-2002	airway resistance| tissue elastance| lung impedance| antigen challenge| inflammation|respiratory system mechanics| induced constriction| lung-mechanics| dry air| rats| bronchoconstriction| histamine| impedance| pressure| behavior	Tomioka, S; Bates, JHT; Irvin, CG	Airway and tissue mechanics in a murine model of asthma: alveolar capsule vs. forced oscillations		JOURNAL OF APPLIED PHYSIOLOGY	airway resistance; tissue elastance; lung impedance; antigen challenge; inflammation	RESPIRATORY SYSTEM MECHANICS; INDUCED CONSTRICTION; LUNG-MECHANICS; DRY AIR; RATS; BRONCHOCONSTRICTION; HISTAMINE; IMPEDANCE; PRESSURE; BEHAVIOR	To better address the functional consequences of inflammation on bronchial responsiveness, we studied two groups of BALB/c mice: a nonimmunized control group (n = 8) and a group immunized and challenged with inhaled ovalbumin (n = 8). An alveolar capsule (AC) measured airway resistance (Raw(AC)) and lung elastance (EL). A forced oscillation (FO) technique independently estimated airway resistance (RawFO) and a parameter H-ti related to tissue elastance. Ovalbumin-immunized and -challenged mice had increased numbers of eosinophils in bronchoalveolar lavage and increased responsiveness to methacholine (MCh). Corresponding parameters from the AC and FO techniques were correlated: RawAC vs. RawFO (r = 0.76) and EL vs. H-ti (r = 0.88, P < 0.0001 in all cases). AC and FO techniques showed significant increases in tissue elastance in response to MCh but no significant increases in airway resistance. These results demonstrated that the AC and FO techniques yield essentially equivalent results in mice, even when the lung is inhomogeneous, and that the bronchoconstrictive responses to MCh and inflammation in mice are predominantly located in the lung periphery.	39	153	2002	8	10.1152/japplphysiol.01129.2001	Physiology; Sport Sciences
Ventilation and health in non-industrial indoor environments: report from a European Multidisciplinary Scientific Consensus Meeting (EUROVEN). Scientific literature on the effects of ventilation on health, comfort, and productivity in non-industrial indoor environments (offices, schools, homes, etc.) has been reviewed by a multidisciplinary group of European scientists, called EUROVEN, with expertise in medicine, epidemiology, toxicology, and engineering. The group reviewed 105 papers published in peer-reviewed scientific journals and judged 30 as conclusive, providing sufficient information on ventilation, health effects, data processing, and reporting, 14 as providing relevant background information on the issue, 43 as relevant but non-informative or inconclusive, and 18 as irrelevant for the issue discussed. Based on the data in papers judged conclusive, the group agreed that ventilation is strongly associated with comfort (perceived air quality) and health [Sick Building Syndrome (SBS) symptoms, inflammation, infections, asthma, allergy, short-term sick leave], and that an association between ventilation and productivity (performance of office work) is indicated. The group also concluded that increasing outdoor air supply rates in non-industrial environments improves perceived air quality; that outdoor air supply rates below 25 l/s per person increase the risk of SBS symptoms, increase short-term sick leave, and decrease productivity among occupants of office buildings; and that ventilation rates above 0.5 air changes per hour (h(-1) ) in homes reduce infestation of house dust mites in Nordic countries. The group concluded additionally that the literature indicates that in buildings with air-conditioning systems there may be an increased risk of SBS symptoms compared with naturally or mechanically ventilated buildings, and that improper maintenance, design, and functioning of air-conditioning systems contributes to increased prevalence of SBS symptoms.. ventilation| outdoor air supply rate| ventilation system| non-industrial indoor environments| offices| schools| homes| health| euroven|sick-building-syndrome| air-exchange-rate| volatile organic-compounds| syndrome sbs symptoms| facial skin symptoms| office buildings| personal factors| case-referent| co2 concentrations| risk indicators.	JUN-2002	ventilation| outdoor air supply rate| ventilation system| non-industrial indoor environments| offices| schools| homes| health| euroven|sick-building-syndrome| air-exchange-rate| volatile organic-compounds| syndrome sbs symptoms| facial skin symptoms| office buildings| personal factors| case-referent| co2 concentrations| risk indicators	Wargocki, P; Sundell, J; Bischof, W; Brundrett, G; Fanger, PO; Gyntelberg, F; Hanssen, SO; Harrison, P; Pickering, A; Seppanen, O; Wouters, P	Ventilation and health in non-industrial indoor environments: report from a European Multidisciplinary Scientific Consensus Meeting (EUROVEN)		INDOOR AIR	ventilation; outdoor air supply rate; ventilation system; non-industrial indoor environments; offices; schools; homes; health; EUROVEN	SICK-BUILDING-SYNDROME; AIR-EXCHANGE-RATE; VOLATILE ORGANIC-COMPOUNDS; SYNDROME SBS SYMPTOMS; FACIAL SKIN SYMPTOMS; OFFICE BUILDINGS; PERSONAL FACTORS; CASE-REFERENT; CO2 CONCENTRATIONS; RISK INDICATORS	Scientific literature on the effects of ventilation on health, comfort, and productivity in non-industrial indoor environments (offices, schools, homes, etc.) has been reviewed by a multidisciplinary group of European scientists, called EUROVEN, with expertise in medicine, epidemiology, toxicology, and engineering. The group reviewed 105 papers published in peer-reviewed scientific journals and judged 30 as conclusive, providing sufficient information on ventilation, health effects, data processing, and reporting, 14 as providing relevant background information on the issue, 43 as relevant but non-informative or inconclusive, and 18 as irrelevant for the issue discussed. Based on the data in papers judged conclusive, the group agreed that ventilation is strongly associated with comfort (perceived air quality) and health [Sick Building Syndrome (SBS) symptoms, inflammation, infections, asthma, allergy, short-term sick leave], and that an association between ventilation and productivity (performance of office work) is indicated. The group also concluded that increasing outdoor air supply rates in non-industrial environments improves perceived air quality; that outdoor air supply rates below 25 l/s per person increase the risk of SBS symptoms, increase short-term sick leave, and decrease productivity among occupants of office buildings; and that ventilation rates above 0.5 air changes per hour (h(-1) ) in homes reduce infestation of house dust mites in Nordic countries. The group concluded additionally that the literature indicates that in buildings with air-conditioning systems there may be an increased risk of SBS symptoms compared with naturally or mechanically ventilated buildings, and that improper maintenance, design, and functioning of air-conditioning systems contributes to increased prevalence of SBS symptoms.	121	153	2002	16	10.1034/j.1600-0668.2002.01145.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Production of allergenic pollen by ragweed (Ambrosia artemisiifolia L.) is increased in CO2-enriched atmospheres. Background: The potential effects of global climate change on allergenic pollen production are still poorly understood. Objective: To study the direct impact of rising atmospheric CO2 concentrations on ragweed (Ambrosia artemisiifolia L.) pollen production and growth. Methods: In environmentally controlled greenhouses, stands of ragweed plants were grown from seed through flowering stages at both ambient and twice-ambient CO2 levels (350 vs 700 muL L-1). Outcome measures included stand-level total pollen production and end-of-season measures of plant mass,, height, and seed production. Results: A doubling of the atmospheric CO2 concentration stimulated ragweed-pollen production by 61% (P = 0.005). Conclusions: These results suggest that there may be significant increases in exposure to allergenic pollen under the present scenarios of global warming. Further studies may enable public health groups to more accurately evaluate the future risks of hay fever and respiratory diseases (eg, asthma) exacerbated by allergenic pollen, and to develop strategies to mitigate them.. elevated co2| growth| climate| plants| reproduction| metaanalysis| asteraceae| biology| gender| health.	MAR-2002	elevated co2| growth| climate| plants| reproduction| metaanalysis| asteraceae| biology| gender| health	Wayne, P; Foster, S; Connolly, J; Bazzaz, F; Epstein, P	Production of allergenic pollen by ragweed (Ambrosia artemisiifolia L.) is increased in CO2-enriched atmospheres		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		ELEVATED CO2; GROWTH; CLIMATE; PLANTS; REPRODUCTION; METAANALYSIS; ASTERACEAE; BIOLOGY; GENDER; HEALTH	Background: The potential effects of global climate change on allergenic pollen production are still poorly understood. Objective: To study the direct impact of rising atmospheric CO2 concentrations on ragweed (Ambrosia artemisiifolia L.) pollen production and growth. Methods: In environmentally controlled greenhouses, stands of ragweed plants were grown from seed through flowering stages at both ambient and twice-ambient CO2 levels (350 vs 700 muL L-1). Outcome measures included stand-level total pollen production and end-of-season measures of plant mass,, height, and seed production. Results: A doubling of the atmospheric CO2 concentration stimulated ragweed-pollen production by 61% (P = 0.005). Conclusions: These results suggest that there may be significant increases in exposure to allergenic pollen under the present scenarios of global warming. Further studies may enable public health groups to more accurately evaluate the future risks of hay fever and respiratory diseases (eg, asthma) exacerbated by allergenic pollen, and to develop strategies to mitigate them.	35	153	2002	4		Allergy; Immunology
Clinical and immunologic effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, placebo-controlled study. Background: Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy. We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy (SLIT) in asthmatic children with mite-induced respiratory allergy. Methods: Twenty-four patients (age range 8-15 years), suffering from mild to moderate asthma, with single sensitization to mite allergen, were enrolled. After a 1-year observation phase, patients were randomly allocated to one of two groups, and were given SLIT (sublingual-spit) as drops for 2 years according to a double-blind, placebo-controlled (DBPC) design. Symptoms/medication scores (diary card), visual analog scale, and immunologic parameters (house-dust-mite [HDM]-specific IgE, and total HDM-specific IgG and IgG4) were determined during the observation phase and during the DBPC treatment period. Results: Twenty-one patients completed the study. At the beginning of the treatment, no difference in environmental allergenic pressure could be shown between the groups. After 2 years of therapy, there was a significant decrease ill asthmatic symptoms (P = 0.0001) and medication use (P = 0.0001) in the active group compared to the placebo group. The visual analog score on overall asthma symptoms improved in the SLIT group (P = 0.0001), but not in the placebo group. Nevertheless, the immunologic results did not show significant differences in HDM-specific IgE and total HDM-specific IgG or IgG4 between the active and placebo groups (P = NS). No relevant side-effects were recorded throughout the study. Conclusions: Our results suggest that treatment for 2 years with SLIT is clinically safe and effective in significantly decreasing respiratory symptoms in children with mild to moderate asthma sensitized to HDM. On the other hand, the lack of changes of the immunologic parameters calls for further investigations with special reference to kinetics and mechanism(s) of action of this mode of treatment.. asthma| dust-mite allergy| sublingual immunotherapy (slit)|house-dust mite| dermatophagoides-pteronyssinus extract| controlled trial| pollen extract| swallow immunotherapy| efficacy| rhinitis| rhinoconjunctivitis| inflammation.	SEP-2000	asthma| dust-mite allergy| sublingual immunotherapy (slit)|house-dust mite| dermatophagoides-pteronyssinus extract| controlled trial| pollen extract| swallow immunotherapy| efficacy| rhinitis| rhinoconjunctivitis| inflammation	Pajno, GB; Morabito, L; Barberio, G; Parmiani, S	Clinical and immunologic effects of long-term sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, placebo-controlled study		ALLERGY	asthma; dust-mite allergy; sublingual immunotherapy (SLIT)	HOUSE-DUST MITE; DERMATOPHAGOIDES-PTERONYSSINUS EXTRACT; CONTROLLED TRIAL; POLLEN EXTRACT; SWALLOW IMMUNOTHERAPY; EFFICACY; RHINITIS; RHINOCONJUNCTIVITIS; INFLAMMATION	Background: Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy. We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy (SLIT) in asthmatic children with mite-induced respiratory allergy. Methods: Twenty-four patients (age range 8-15 years), suffering from mild to moderate asthma, with single sensitization to mite allergen, were enrolled. After a 1-year observation phase, patients were randomly allocated to one of two groups, and were given SLIT (sublingual-spit) as drops for 2 years according to a double-blind, placebo-controlled (DBPC) design. Symptoms/medication scores (diary card), visual analog scale, and immunologic parameters (house-dust-mite [HDM]-specific IgE, and total HDM-specific IgG and IgG4) were determined during the observation phase and during the DBPC treatment period. Results: Twenty-one patients completed the study. At the beginning of the treatment, no difference in environmental allergenic pressure could be shown between the groups. After 2 years of therapy, there was a significant decrease ill asthmatic symptoms (P = 0.0001) and medication use (P = 0.0001) in the active group compared to the placebo group. The visual analog score on overall asthma symptoms improved in the SLIT group (P = 0.0001), but not in the placebo group. Nevertheless, the immunologic results did not show significant differences in HDM-specific IgE and total HDM-specific IgG or IgG4 between the active and placebo groups (P = NS). No relevant side-effects were recorded throughout the study. Conclusions: Our results suggest that treatment for 2 years with SLIT is clinically safe and effective in significantly decreasing respiratory symptoms in children with mild to moderate asthma sensitized to HDM. On the other hand, the lack of changes of the immunologic parameters calls for further investigations with special reference to kinetics and mechanism(s) of action of this mode of treatment.	35	153	2000	8	10.1034/j.1398-9995.2000.00495.x	Allergy; Immunology
Barriers pediatricians face when using asthma practice guidelines. Objective: To describe barriers to the successful use of the 1997 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines. Methods; We conducted 3 focus groups to understand barriers to the use of 4 recommendations within the NHLBI guidelines (prescription of inhaled corticosteroids, recommendation of daily peak flowmeter use, smoking cessation screening and counseling, and allergen exposure counseling). Participants: Twenty-one pediatricians and 1 nurse practitioner, who each followed an average of 47 patients with asthma, participated. Six participants (27%) had a faculty or adjunct appointment at a medical school. Nineteen (90%) of the 21 pediatricians were board certified. Results: We identified 171 comments about barriers to adherence. Type of recommendation and physician year of graduation from medical school were related to which barrier was prominent. For corticosteroid prescription, senior physicians mentioned lack of agreement, whereas younger physicians described lack of confidence in dosing or recognizing contraindications. For peak flowmeter use, senior physicians emphasized lack of training. Only senior physicians described the inertia of previous practice as a barrier. All groups mentioned time limitations. Conclusions: Efforts to improve adherence to asthma guidelines should consider the range of barriers that pediatricians face, such as lack of awareness, familiarity, or agreement, and external barriers owing to environmental, guideline, or patient factors. In addition, this study documents barriers not previously considered, such as lack of self-efficacy, lack of outcome expectancy, and inertia of previous practice, that prevent adherence, Be cause type of recommendation and physician demographics are related to which barriers are prominent, interventions to improve NHLBI guideline adherence should be tailored to these factors.. clinical-practice guidelines| inner-city children| physicians attitudes| randomized trial| care| implementation| education| intervention| management| parents.	JUL-2000	clinical-practice guidelines| inner-city children| physicians attitudes| randomized trial| care| implementation| education| intervention| management| parents	Cabana, MD; Ebel, BE; Cooper-Patrick, L; Powe, NR; Rubin, HR; Rand, CS	Barriers pediatricians face when using asthma practice guidelines		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		CLINICAL-PRACTICE GUIDELINES; INNER-CITY CHILDREN; PHYSICIANS ATTITUDES; RANDOMIZED TRIAL; CARE; IMPLEMENTATION; EDUCATION; INTERVENTION; MANAGEMENT; PARENTS	Objective: To describe barriers to the successful use of the 1997 National Heart, Lung, and Blood Institute (NHLBI) asthma guidelines. Methods; We conducted 3 focus groups to understand barriers to the use of 4 recommendations within the NHLBI guidelines (prescription of inhaled corticosteroids, recommendation of daily peak flowmeter use, smoking cessation screening and counseling, and allergen exposure counseling). Participants: Twenty-one pediatricians and 1 nurse practitioner, who each followed an average of 47 patients with asthma, participated. Six participants (27%) had a faculty or adjunct appointment at a medical school. Nineteen (90%) of the 21 pediatricians were board certified. Results: We identified 171 comments about barriers to adherence. Type of recommendation and physician year of graduation from medical school were related to which barrier was prominent. For corticosteroid prescription, senior physicians mentioned lack of agreement, whereas younger physicians described lack of confidence in dosing or recognizing contraindications. For peak flowmeter use, senior physicians emphasized lack of training. Only senior physicians described the inertia of previous practice as a barrier. All groups mentioned time limitations. Conclusions: Efforts to improve adherence to asthma guidelines should consider the range of barriers that pediatricians face, such as lack of awareness, familiarity, or agreement, and external barriers owing to environmental, guideline, or patient factors. In addition, this study documents barriers not previously considered, such as lack of self-efficacy, lack of outcome expectancy, and inertia of previous practice, that prevent adherence, Be cause type of recommendation and physician demographics are related to which barriers are prominent, interventions to improve NHLBI guideline adherence should be tailored to these factors.	46	153	2000	9		Pediatrics
The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study. Background: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). Objective: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. Methods: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. Results: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > \Z\ less than or equal to 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. Conclusion: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.. aeroallergens| atopic eczema| atopy patch test| european multicenter|house-dust mite| epidermal langerhans cells| dermatitis patients| double-blind| skin| frequency| avoidance| induction| extracts| children.	DEC-2004	aeroallergens| atopic eczema| atopy patch test| european multicenter|house-dust mite| epidermal langerhans cells| dermatitis patients| double-blind| skin| frequency| avoidance| induction| extracts| children	Darsow, U; Laifaoui, J; Kerschenlohr, K; Wollenberg, A; Przybilla, B; Wuthrich, B; Borelli, S; Giusti, F; Seidenari, S; Drzimalla, K; Simon, D; Disch, R; Borelli, S; Devillers, ACA; Oranje, AP; De Raeve, L; Hachem, JP; Dangoisse, C; Blondeel, A; Song, M; Breuer, K; Wulf, A; Werfel, T; Roul, S; Taieb, A; Bolhaar, S; Bruijnzeel-Koomen, C; Bronnimann, M; Braathen, LR; Didierlaurent, A; Andre, C; Ring, J	The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study		ALLERGY	aeroallergens; atopic eczema; atopy patch test; European multicenter	HOUSE-DUST MITE; EPIDERMAL LANGERHANS CELLS; DERMATITIS PATIENTS; DOUBLE-BLIND; SKIN; FREQUENCY; AVOIDANCE; INDUCTION; EXTRACTS; CHILDREN	Background: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). Objective: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. Methods: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. Results: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > \Z\ less than or equal to 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. Conclusion: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.	39	152	2004	8	10.1111/j.1398-9995.2004.00556.x	Allergy; Immunology
Health effects of diesel exhaust emissions - a mixture of air pollutants of worldwide concern. Diesel exhaust is a mixture of particles and gases. It contains more than several hundred different organic and inorganic components, including many chemicals that have been designated as toxic air pollutants. Because mutagens and carcinogens are present in both the gaseous and particulate components, lung cancer has been the focus of attention as a health risk in animal and human research. Moreover, since the epidemiologic data suggest carcinogenicity in humans, and the diesel exhaust exposure data in evaluations in rats by NIOSH, IARC, WHO, and the California EPA, are said to demonstrate or support carcinogenicity, agencies have designated them as latent occupational carcinogens (NIOSH) or toxic air pollutants (California EPA). In regard to their non-carcinogenic effects, a contribution to airway inflammation and allergies, and in relation to disease, the possibility of contracting asthma and chronic bronchitis, have been investigated both experimentally and epidemiologically, and concern has increased about their health effects, particularly in children. (C) 2002 Published by Elsevier Science Ireland Ltd.. health effects| diesel exhaust| diesel particles.	DEC 27-2002	health effects| diesel exhaust| diesel particles	Kagawa, J	Health effects of diesel exhaust emissions - a mixture of air pollutants of worldwide concern		TOXICOLOGY	health effects; diesel exhaust; diesel particles		Diesel exhaust is a mixture of particles and gases. It contains more than several hundred different organic and inorganic components, including many chemicals that have been designated as toxic air pollutants. Because mutagens and carcinogens are present in both the gaseous and particulate components, lung cancer has been the focus of attention as a health risk in animal and human research. Moreover, since the epidemiologic data suggest carcinogenicity in humans, and the diesel exhaust exposure data in evaluations in rats by NIOSH, IARC, WHO, and the California EPA, are said to demonstrate or support carcinogenicity, agencies have designated them as latent occupational carcinogens (NIOSH) or toxic air pollutants (California EPA). In regard to their non-carcinogenic effects, a contribution to airway inflammation and allergies, and in relation to disease, the possibility of contracting asthma and chronic bronchitis, have been investigated both experimentally and epidemiologically, and concern has increased about their health effects, particularly in children. (C) 2002 Published by Elsevier Science Ireland Ltd.	13	84	2002	5	10.1016/S0300-483X(02)00461-4	Pharmacology & Pharmacy; Toxicology
Randomised controlled trial of home based care of patients with chronic obstructive pulmonary disease. Objectives To evaluate usefulness of limited community based care for patients with chronic obstructive pulmonary disease after discharge from hospital. Design Randomised controlled trial. Setting Liverpool Health Service and Macarthur Health Service in outer metropolitan Sydney between September 1999 and July 2000. Participants 177 patients randomised into an intervention group (84 patients) and a control group (93 patients) which received current usual care. Interventions Home visits by community nurse at one and four weeks after discharge and preventive general practitioner care. Main outcome measures Frequency of patients' presentation and admission to hospital; changes in patients' disease-specific quality of life, measured with St George's respiratory questionnaire, over three months after discharge; patients' knowledge of illness, self management, and satisfaction with care at discharge and three months later; frequency of general practitioner and nurse visits and their satisfaction with care. Results Intervention and control groups showed no differences in presentation or admission to hospital or in overall functional status. However, the intervention group improved their activity scores and the control group worsened their symptom scores. While intervention group patients received more visits from community nurses and were more satisfied with their care, involvement of general practitioners was much less (with only 31% (22) remembering receiving a care plan). Patients in the intervention group had higher knowledge scores and were more satisfied. There were no differences in general practitioner visits or management. Conclusions This brief intervention after acute care improved patients' knowledge and some aspects of quality of life. However, it failed to prevent presentation and readmission to hospital.. air-flow limitation| respiratory questionnaire| copd| exacerbations| program| asthma.	OCT 26-2002	air-flow limitation| respiratory questionnaire| copd| exacerbations| program| asthma	Hermiz, O; Comino, E; Marks, G; Daffurn, K; Wilson, S; Harris, M	Randomised controlled trial of home based care of patients with chronic obstructive pulmonary disease		BRITISH MEDICAL JOURNAL		AIR-FLOW LIMITATION; RESPIRATORY QUESTIONNAIRE; COPD; EXACERBATIONS; PROGRAM; ASTHMA	Objectives To evaluate usefulness of limited community based care for patients with chronic obstructive pulmonary disease after discharge from hospital. Design Randomised controlled trial. Setting Liverpool Health Service and Macarthur Health Service in outer metropolitan Sydney between September 1999 and July 2000. Participants 177 patients randomised into an intervention group (84 patients) and a control group (93 patients) which received current usual care. Interventions Home visits by community nurse at one and four weeks after discharge and preventive general practitioner care. Main outcome measures Frequency of patients' presentation and admission to hospital; changes in patients' disease-specific quality of life, measured with St George's respiratory questionnaire, over three months after discharge; patients' knowledge of illness, self management, and satisfaction with care at discharge and three months later; frequency of general practitioner and nurse visits and their satisfaction with care. Results Intervention and control groups showed no differences in presentation or admission to hospital or in overall functional status. However, the intervention group improved their activity scores and the control group worsened their symptom scores. While intervention group patients received more visits from community nurses and were more satisfied with their care, involvement of general practitioners was much less (with only 31% (22) remembering receiving a care plan). Patients in the intervention group had higher knowledge scores and were more satisfied. There were no differences in general practitioner visits or management. Conclusions This brief intervention after acute care improved patients' knowledge and some aspects of quality of life. However, it failed to prevent presentation and readmission to hospital.	22	84	2002	6	10.1136/bmj.325.7370.938	General & Internal Medicine
Monocyte-derived dendritic cells induce a house dust mite-specific Th2 allergic inflammation in the lung of humanized SCID mice: Involvement of CCR7. In rodents, airway dendritic cells (DCs) capture inhaled Ag, undergo maturation, and migrate to the draining mediastinal lymph nodes (MLN) to initiate the Ag-specific T cell response. However, the role of human DCs in the pathogenesis of the Th2 cell-mediated disease asthma remains to be clarified. Here, by using SCID mice engrafted with T cells from either house dust mite (HDM)-allergic patients or healthy donors, we show that DCs pulsed with Der p 1, one of the major allergens or HDM, and injected intratracheally into naive animals migrated into the MLN. In the NILN, Der p I-pulsed DCs from allergic patients induced the proliferation of IL-4-producing CD4(+) T cells, whereas those from healthy donors induced IFN-gamma-secreting cells. In reconstituted human PBM C-reconstituted SCID mice primed with pulsed DCs from allergic patients, repeated exposure to aerosols of HDM induced 1) a strong pulmonary inflammatory reaction rich in T cells and eosinophils, 2) an increase in IL-4 and IL-5 production in the lung lavage fluid, and 3) increased IgE production compared with that in mice primed with unpulsed DCs. All these effects were reduced following in vivo neutralization of the CCR7 ligand secondary lymphoid tissue chemokine. These data in human PBMC-reconstituted SCID mice show that monocyte-derived DCs might play a key role in the pathogenesis of the pulmonary allergic response by inducing Th2 effector function following migration to the MLN.. eosinophilic airway inflammation| lymph-nodes| inhaled antigen| intratracheal instillation| lacking expression| respiratory-tract| responses| chemokine| asthma| model.	AUG 1-2002	eosinophilic airway inflammation| lymph-nodes| inhaled antigen| intratracheal instillation| lacking expression| respiratory-tract| responses| chemokine| asthma| model	Hammad, H; Lambrecht, BN; Pochard, P; Gosset, P; Marquillies, P; Tonnel, AB; Pestel, J	Monocyte-derived dendritic cells induce a house dust mite-specific Th2 allergic inflammation in the lung of humanized SCID mice: Involvement of CCR7		JOURNAL OF IMMUNOLOGY		EOSINOPHILIC AIRWAY INFLAMMATION; LYMPH-NODES; INHALED ANTIGEN; INTRATRACHEAL INSTILLATION; LACKING EXPRESSION; RESPIRATORY-TRACT; RESPONSES; CHEMOKINE; ASTHMA; MODEL	In rodents, airway dendritic cells (DCs) capture inhaled Ag, undergo maturation, and migrate to the draining mediastinal lymph nodes (MLN) to initiate the Ag-specific T cell response. However, the role of human DCs in the pathogenesis of the Th2 cell-mediated disease asthma remains to be clarified. Here, by using SCID mice engrafted with T cells from either house dust mite (HDM)-allergic patients or healthy donors, we show that DCs pulsed with Der p 1, one of the major allergens or HDM, and injected intratracheally into naive animals migrated into the MLN. In the NILN, Der p I-pulsed DCs from allergic patients induced the proliferation of IL-4-producing CD4(+) T cells, whereas those from healthy donors induced IFN-gamma-secreting cells. In reconstituted human PBM C-reconstituted SCID mice primed with pulsed DCs from allergic patients, repeated exposure to aerosols of HDM induced 1) a strong pulmonary inflammatory reaction rich in T cells and eosinophils, 2) an increase in IL-4 and IL-5 production in the lung lavage fluid, and 3) increased IgE production compared with that in mice primed with unpulsed DCs. All these effects were reduced following in vivo neutralization of the CCR7 ligand secondary lymphoid tissue chemokine. These data in human PBMC-reconstituted SCID mice show that monocyte-derived DCs might play a key role in the pathogenesis of the pulmonary allergic response by inducing Th2 effector function following migration to the MLN.	40	84	2002	11		Immunology
The safety of celecoxib in patients with aspirin-sensitive asthma. Objective. To determine whether celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, cross-reacts in patients with aspirin-exacerbated respiratory disease (AERD) with asthma. Methods. Sixty patients with asthma underwent double-blinded, placebo-controlled oral challenges with celecoxib (100 mg, 200 mg, and 2 placebos) over 48 hours in our General Clinical Research Center. The next day, sensitivity to acetylsalicylic acid (ASA) was proven in all patients with the use of single-blinded ASA challenges. Results. None of the 60 patients experienced any symptoms, changes in nasal examinations, or declines in forced expiratory volume in 1 second during the celecoxib challenges. All 60 patients experienced oculo-nasal and/or asthmatic reactions to ASA, with a mean provoking dose of 69 mg. The exact 1-sided confidence interval for the probability of celecoxib inducing cross-reactions in AERD patients was calculated to be between 0% and 5%. Conclusion. Cross-reactivity between ASA and celecoxib does not occur in patients with AERD. These results do not preclude the possibility of other types of immune reactions occurring with celecoxib after prior exposure. Our results add to the growing body of evidence that inhibition of COX-1 is a critical initiating event in the precipitation of respiratory reactions in AERD patients following ingestion of nonsteroidal anti-inflammatory drugs.. cyclooxygenase-2 inhibitor| intolerant patients| cross-sensitivity| cox-2| pathogenesis| expression| drugs.	AUG-2002	cyclooxygenase-2 inhibitor| intolerant patients| cross-sensitivity| cox-2| pathogenesis| expression| drugs	Woessner, KM; Simon, RA; Stevenson, DD	The safety of celecoxib in patients with aspirin-sensitive asthma		ARTHRITIS AND RHEUMATISM		CYCLOOXYGENASE-2 INHIBITOR; INTOLERANT PATIENTS; CROSS-SENSITIVITY; COX-2; PATHOGENESIS; EXPRESSION; DRUGS	Objective. To determine whether celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, cross-reacts in patients with aspirin-exacerbated respiratory disease (AERD) with asthma. Methods. Sixty patients with asthma underwent double-blinded, placebo-controlled oral challenges with celecoxib (100 mg, 200 mg, and 2 placebos) over 48 hours in our General Clinical Research Center. The next day, sensitivity to acetylsalicylic acid (ASA) was proven in all patients with the use of single-blinded ASA challenges. Results. None of the 60 patients experienced any symptoms, changes in nasal examinations, or declines in forced expiratory volume in 1 second during the celecoxib challenges. All 60 patients experienced oculo-nasal and/or asthmatic reactions to ASA, with a mean provoking dose of 69 mg. The exact 1-sided confidence interval for the probability of celecoxib inducing cross-reactions in AERD patients was calculated to be between 0% and 5%. Conclusion. Cross-reactivity between ASA and celecoxib does not occur in patients with AERD. These results do not preclude the possibility of other types of immune reactions occurring with celecoxib after prior exposure. Our results add to the growing body of evidence that inhibition of COX-1 is a critical initiating event in the precipitation of respiratory reactions in AERD patients following ingestion of nonsteroidal anti-inflammatory drugs.	32	84	2002	6	10.1002/art.10426	Rheumatology
Extended NO analysis applied to patients with COPD, allergic asthma and allergic rhinitis. The recommended method to measure exhaled nitric oxide (NO) cannot reveal the source of NO production. We applied a model based on the classical Fick's first law of diffusion to partition NO in the lungs. The aim was to develop a simple and robust solution algorithm with a data quality control feature, and apply it to patients with known alterations in exhaled NO. Subjects with allergic rhinitis, allergic asthma, chronic obstructive pulmonary disease (COPD) smokers and controls were investigated. NO was measured at three expiratory flow rates. An iteration method was developed to partition NO. The airway tissue content of NO was increased in asthma, 144 +/- 80 ppb (P = 0(.)04) and decreased in smokers, 56 +/- 36 ppb (P = 0(.)02). There was no difference between subjects with rhinitis, 98 +/- 40 ppb and controls, 98 +/- 44 ppb. The airway transfer rate was increased in allergic asthma and allergic rhinithis, 12 +/- 4 vs. 12 +/- 5 ml sec(-1), compared to controls, 8 +/- 2 ml sec(-1) (P < 0(.)001). The alveolar levels were no different from controls, 2 +/- 1 ppb. In COPD the alveolar levels were increased, 4 +/- 2 ppb (P < 0(.)001). Extended NO analysis reveals from where in the respiratory system NO is generated. Hence, this new test can be added to the tools the physician has for the diagnosis and treatment of patients with respiratory disorders. (C) 2001 Harcourt Publishers Ltd.. nitric oxide| asthma| allergic rhinitis| smoker| copd| airway inflammation| method|exhaled nitric-oxide| responsiveness| disease| airways| air.	JAN-2002	nitric oxide| asthma| allergic rhinitis| smoker| copd| airway inflammation| method|exhaled nitric-oxide| responsiveness| disease| airways| air	Hogman, M; Holmkvist, T; Wegener, T; Emtner, M; Andersson, M; Hedenstrom, H; Merilainen, P	Extended NO analysis applied to patients with COPD, allergic asthma and allergic rhinitis		RESPIRATORY MEDICINE	nitric oxide; asthma; allergic rhinitis; smoker; COPD; airway inflammation; method	EXHALED NITRIC-OXIDE; RESPONSIVENESS; DISEASE; AIRWAYS; AIR	The recommended method to measure exhaled nitric oxide (NO) cannot reveal the source of NO production. We applied a model based on the classical Fick's first law of diffusion to partition NO in the lungs. The aim was to develop a simple and robust solution algorithm with a data quality control feature, and apply it to patients with known alterations in exhaled NO. Subjects with allergic rhinitis, allergic asthma, chronic obstructive pulmonary disease (COPD) smokers and controls were investigated. NO was measured at three expiratory flow rates. An iteration method was developed to partition NO. The airway tissue content of NO was increased in asthma, 144 +/- 80 ppb (P = 0(.)04) and decreased in smokers, 56 +/- 36 ppb (P = 0(.)02). There was no difference between subjects with rhinitis, 98 +/- 40 ppb and controls, 98 +/- 44 ppb. The airway transfer rate was increased in allergic asthma and allergic rhinithis, 12 +/- 4 vs. 12 +/- 5 ml sec(-1), compared to controls, 8 +/- 2 ml sec(-1) (P < 0(.)001). The alveolar levels were no different from controls, 2 +/- 1 ppb. In COPD the alveolar levels were increased, 4 +/- 2 ppb (P < 0(.)001). Extended NO analysis reveals from where in the respiratory system NO is generated. Hence, this new test can be added to the tools the physician has for the diagnosis and treatment of patients with respiratory disorders. (C) 2001 Harcourt Publishers Ltd.	18	84	2002	7	10.1053/rmed.2001.1204	Cardiovascular System & Cardiology; Respiratory System
The dual effect of the particulate and organic components of diesel exhaust particles on the alteration of pulmonary immune/inflammatory responses and metabolic enzymes. Exposure to diesel exhaust particles (DEP) is an environmental and occupational health concern. This review examines the cellular actions of the organic and the particulate components of DEP in the development of various lung diseases. Both the organic and the particulate components cause oxidant lung injury. The particulate component is known to induce alveolar epithelial damage, alter thiol levels in alveolar macrophages (AM) and lymphocytes, and activate AM in the production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The organic component, on the other hand, is shown to generate intracellular ROS, leading to a variety of cellular responses including apoptosis. There are a number of differences between the biological actions exerted by these two components. The organic component is responsible-for DEP induction of cytochrome P450 family 1 enzymes that are critical to the polycyclic aromatic hydrocarbons (PAH) and nitro-PAH metabolism in the lung as well as in the liver. The particulate component, on the other hand, causes a sustained down-regulation of CYP2B1 in the rat lung. The significance of this effect on pulmonary metabolism of xenobiotics and endobiotics remains to be seen, but may prove to be an important factor governing the interplay of the pulmonary metabolic and inflammatory systems. Long-term exposures to various particles including DEP, carbon black (CB), TiO(2), and washed DEP devoid of the organic content, have been shown to produce similar tumorigenic responses in rodents. There is a lack of correlation between tumor development and DEP chemical-derived DNA adduct formation. But the organic component has been shown to generate ROS that produce 8-hydroxydeoxyguanosine (8-OHdG) in cell culture. The organic, but not the particulate, component of DEP suppresses the production of pro-inflammatory cytokines by AM and the development of Th1 cell-mediated immunity. The mechanism for this effect is not yet clear, but may involve the induction of heme oxygenase-1 (HO-1), a cellular genetic response to oxidative stress. Both the organic and the particulate components of DEP enhance respiratory allergic sensitization. Part of the DEP effects may be due to a depletion of glutathione in lymphocytes. The organic component, which is shown to induce IL-4 and IL-10 productions, may skew the immunity toward Th2 response, whereas the particulate component may stimulate both the Th1 and Th2 responses. In conclusion, the literature shows that the particulate and organic components of DEP exhibit different biological actions but both involve the induction of cellular oxidative stress. Together, these effects inhibit cell-mediated immunity toward infectious agents, exacerbate respiratory allergy, cause DNA damage, and under long-term exposure, induce the development of lung tumors.. diesel exhaust particles (dep)| particulate| organic extract| reactive oxygen species (ros)| metabolic enzymes| th1 and th2 immune responses| cytokines| infection| allergy| lung tumors|tumor-necrosis-factor| cytochrome p450 reductase| rat alveolar macrophages| cell-mediated-immunity| oxidative dna-damage| carbon-black| nitric-oxide| listeria-monocytogenes| heme oxygenase-1| in-vivo.	2002	diesel exhaust particles (dep)| particulate| organic extract| reactive oxygen species (ros)| metabolic enzymes| th1 and th2 immune responses| cytokines| infection| allergy| lung tumors|tumor-necrosis-factor| cytochrome p450 reductase| rat alveolar macrophages| cell-mediated-immunity| oxidative dna-damage| carbon-black| nitric-oxide| listeria-monocytogenes| heme oxygenase-1| in-vivo	Ma, JYC; Ma, JKH	The dual effect of the particulate and organic components of diesel exhaust particles on the alteration of pulmonary immune/inflammatory responses and metabolic enzymes		JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS	diesel exhaust particles (DEP); particulate; organic extract; reactive oxygen species (ROS); metabolic enzymes; th1 and th2 immune responses; cytokines; infection; allergy; lung tumors	TUMOR-NECROSIS-FACTOR; CYTOCHROME P450 REDUCTASE; RAT ALVEOLAR MACROPHAGES; CELL-MEDIATED-IMMUNITY; OXIDATIVE DNA-DAMAGE; CARBON-BLACK; NITRIC-OXIDE; LISTERIA-MONOCYTOGENES; HEME OXYGENASE-1; IN-VIVO	Exposure to diesel exhaust particles (DEP) is an environmental and occupational health concern. This review examines the cellular actions of the organic and the particulate components of DEP in the development of various lung diseases. Both the organic and the particulate components cause oxidant lung injury. The particulate component is known to induce alveolar epithelial damage, alter thiol levels in alveolar macrophages (AM) and lymphocytes, and activate AM in the production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The organic component, on the other hand, is shown to generate intracellular ROS, leading to a variety of cellular responses including apoptosis. There are a number of differences between the biological actions exerted by these two components. The organic component is responsible-for DEP induction of cytochrome P450 family 1 enzymes that are critical to the polycyclic aromatic hydrocarbons (PAH) and nitro-PAH metabolism in the lung as well as in the liver. The particulate component, on the other hand, causes a sustained down-regulation of CYP2B1 in the rat lung. The significance of this effect on pulmonary metabolism of xenobiotics and endobiotics remains to be seen, but may prove to be an important factor governing the interplay of the pulmonary metabolic and inflammatory systems. Long-term exposures to various particles including DEP, carbon black (CB), TiO(2), and washed DEP devoid of the organic content, have been shown to produce similar tumorigenic responses in rodents. There is a lack of correlation between tumor development and DEP chemical-derived DNA adduct formation. But the organic component has been shown to generate ROS that produce 8-hydroxydeoxyguanosine (8-OHdG) in cell culture. The organic, but not the particulate, component of DEP suppresses the production of pro-inflammatory cytokines by AM and the development of Th1 cell-mediated immunity. The mechanism for this effect is not yet clear, but may involve the induction of heme oxygenase-1 (HO-1), a cellular genetic response to oxidative stress. Both the organic and the particulate components of DEP enhance respiratory allergic sensitization. Part of the DEP effects may be due to a depletion of glutathione in lymphocytes. The organic component, which is shown to induce IL-4 and IL-10 productions, may skew the immunity toward Th2 response, whereas the particulate component may stimulate both the Th1 and Th2 responses. In conclusion, the literature shows that the particulate and organic components of DEP exhibit different biological actions but both involve the induction of cellular oxidative stress. Together, these effects inhibit cell-mediated immunity toward infectious agents, exacerbate respiratory allergy, cause DNA damage, and under long-term exposure, induce the development of lung tumors.	121	84	2002	31	10.1081/GNC-120016202	Oncology; Environmental Sciences & Ecology; Toxicology
Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1 : Th2 cytokine ratios. Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P=0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P=0.03) and no change in interferon-gamma (IFN-gamma) mRNA(+) cells (P=0.2) in the nasal mucosa. In contrast, in the immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P=0.3) and IL-5 mRNA(+) cells (P=0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P=0.03). Furthermore, clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P=0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.. messenger-rna expression| seasonal allergic rhinitis| cd4+ t-cells| immunological changes| interferon-gamma| antibody-levels| primary culture| il-4 production| lymphocytes-t| in-vitro.	JAN-2002	messenger-rna expression| seasonal allergic rhinitis| cd4+ t-cells| immunological changes| interferon-gamma| antibody-levels| primary culture| il-4 production| lymphocytes-t| in-vitro	Wachholz, PA; Nouri-Aria, KT; Wilson, DR; Walker, SM; Verhoef, A; Till, SJ; Durham, SR	Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1 : Th2 cytokine ratios		IMMUNOLOGY		MESSENGER-RNA EXPRESSION; SEASONAL ALLERGIC RHINITIS; CD4+ T-CELLS; IMMUNOLOGICAL CHANGES; INTERFERON-GAMMA; ANTIBODY-LEVELS; PRIMARY CULTURE; IL-4 PRODUCTION; LYMPHOCYTES-T; IN-VITRO	Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P=0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P=0.03) and no change in interferon-gamma (IFN-gamma) mRNA(+) cells (P=0.2) in the nasal mucosa. In contrast, in the immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P=0.3) and IL-5 mRNA(+) cells (P=0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P=0.03). Furthermore, clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P=0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.	44	84	2002	7	10.1046/j.1365-2567.2002.01338.x	Immunology
Ethnic differences in asthma and associated phenotypes: Collaborative Study on the Genetics of Asthma. Background: In the Collaborative Study on the Genetics of Asthma, 314 families with 2584 subjects were characterized for asthma and allergy. Objective: The purpose of this investigation was to examine clinical heterogeneity observed in asthma and allergic characteristics among 3 ethnic groups (African American, white, and Hispanic family members). Methods: pulmonary function parameters and asthma-associated phenotypes were compared among the ethnic groups. Results: In comparison with the other groups, African American sibling pairs had a significantly lower baseline FEV, percent of predicted (P = .0001) and a higher rate of skin test reactivity to cockroach allergen (P = .0001); Hispanic sibling pairs had significantly more skin reactivity overall (P = .001); and white sibling pairs had significantly lower total serum IgE (P < .05). In addition, there were significantly more relatives with asthma among the African American families than among the white and the Hispanic families (P = .001). Conclusion: Although different environmental backgrounds should be considered, these clinical differences could be due to differences in genetic susceptibility among the ethnic groups, such as those suggested by our previous genome screen.. asthma| bronchial hyperresponsiveness| atopy| ethnic differences|skin-test reactivity| genome-wide search| serum ige levels| socioeconomic-status| cockroach allergen| childhood asthma| indoor allergens| children| race| severity.	SEP-2001	asthma| bronchial hyperresponsiveness| atopy| ethnic differences|skin-test reactivity| genome-wide search| serum ige levels| socioeconomic-status| cockroach allergen| childhood asthma| indoor allergens| children| race| severity	Lester, LA; Rich, SS; Blumenthal, MN; Togias, A; Murphy, S; Malveaux, F; Miller, ME; Dunston, GM; Solway, J; Wolf, RL; Samet, JM; Marsh, DG; Meyers, DA; Ober, C; Bleecker, ER	Ethnic differences in asthma and associated phenotypes: Collaborative Study on the Genetics of Asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; bronchial hyperresponsiveness; atopy; ethnic differences	SKIN-TEST REACTIVITY; GENOME-WIDE SEARCH; SERUM IGE LEVELS; SOCIOECONOMIC-STATUS; COCKROACH ALLERGEN; CHILDHOOD ASTHMA; INDOOR ALLERGENS; CHILDREN; RACE; SEVERITY	Background: In the Collaborative Study on the Genetics of Asthma, 314 families with 2584 subjects were characterized for asthma and allergy. Objective: The purpose of this investigation was to examine clinical heterogeneity observed in asthma and allergic characteristics among 3 ethnic groups (African American, white, and Hispanic family members). Methods: pulmonary function parameters and asthma-associated phenotypes were compared among the ethnic groups. Results: In comparison with the other groups, African American sibling pairs had a significantly lower baseline FEV, percent of predicted (P = .0001) and a higher rate of skin test reactivity to cockroach allergen (P = .0001); Hispanic sibling pairs had significantly more skin reactivity overall (P = .001); and white sibling pairs had significantly lower total serum IgE (P < .05). In addition, there were significantly more relatives with asthma among the African American families than among the white and the Hispanic families (P = .001). Conclusion: Although different environmental backgrounds should be considered, these clinical differences could be due to differences in genetic susceptibility among the ethnic groups, such as those suggested by our previous genome screen.	35	84	2001	6	10.1067/mai.2001.117796	Allergy; Immunology
The Childhood Asthma Prevention Study (CAPS): Design and research protocol of a randomized trial for the primary prevention of asthma. The Childhood Asthma Prevention Study is a randomized controlled trial to measure whether the incidence of atopy and asthma can be reduced by house dust mite allergen reduction, a diet supplemented with omega-3 fatty acids, or a combination of both interventions. Six hundred and sixteen pregnant women whose unborn children were at high risk of developing asthma because of a family history were randomized prenatally. Study groups are as follows: Group A (placebo diet intervention, no house dust mite reduction), Group B (placebo diet intervention, active house dust mite reduction), Group C (active diet intervention, no house dust mite reduction), and Group D (active diet intervention, active house dust mite reduction). The house dust mite reduction intervention comprises use of physical and chemical methods to reduce allergen contact. The dietary intervention comprises use of a daily oil supplement from 6 months or at onset of bottle-feeding, and use of margarine and cooking oils based on sunflower or canola oils to increase omega-3 dietary intake. Data is collected quarterly until the infant is 1 year old and then half yearly until age 5 years. Questionnaires are used ti, collect respiratory illness history and information about diet and home environment. Dust is collected from the child's bed and bedroom and playroom floors. Blinded assessments are conducted at 18 months, 3 years, and 5 years. Skin prick tests to common allergens, blood tests, and detailed illness, medication use, and vaccination histories are collected. Primary outcomes will be the development of allergic sensitization and the presence and severity of asthma. This study is designed to measure the effectiveness of allergen reduction and dietary supplementation, both separately and in combination, for the primary prevention of atopy and asthma. The results of this study may have important implications for public health policies to reduce the incidence of childhood asthma. (C) Elsevier Science Inc. 2001.. asthma| atopy| allergen avoidance| benzyl benzoate| fatty acid supplementation| house dust mite| primary prevention of asthma|food-allergen avoidance| dust mite allergens| bronchial hyperresponsiveness| respiratory symptoms| population-sample| fatty-acids| children| infancy| atopy| risk.	JUN-2001	asthma| atopy| allergen avoidance| benzyl benzoate| fatty acid supplementation| house dust mite| primary prevention of asthma|food-allergen avoidance| dust mite allergens| bronchial hyperresponsiveness| respiratory symptoms| population-sample| fatty-acids| children| infancy| atopy| risk	Mihrshahi, S; Peat, JK; Webb, K; Tovey, ER; Marks, GB; Mellis, CM; Leeder, SR	The Childhood Asthma Prevention Study (CAPS): Design and research protocol of a randomized trial for the primary prevention of asthma		CONTROLLED CLINICAL TRIALS	Asthma; atopy; allergen avoidance; benzyl benzoate; fatty acid supplementation; house dust mite; primary prevention of asthma	FOOD-ALLERGEN AVOIDANCE; DUST MITE ALLERGENS; BRONCHIAL HYPERRESPONSIVENESS; RESPIRATORY SYMPTOMS; POPULATION-SAMPLE; FATTY-ACIDS; CHILDREN; INFANCY; ATOPY; RISK	The Childhood Asthma Prevention Study is a randomized controlled trial to measure whether the incidence of atopy and asthma can be reduced by house dust mite allergen reduction, a diet supplemented with omega-3 fatty acids, or a combination of both interventions. Six hundred and sixteen pregnant women whose unborn children were at high risk of developing asthma because of a family history were randomized prenatally. Study groups are as follows: Group A (placebo diet intervention, no house dust mite reduction), Group B (placebo diet intervention, active house dust mite reduction), Group C (active diet intervention, no house dust mite reduction), and Group D (active diet intervention, active house dust mite reduction). The house dust mite reduction intervention comprises use of physical and chemical methods to reduce allergen contact. The dietary intervention comprises use of a daily oil supplement from 6 months or at onset of bottle-feeding, and use of margarine and cooking oils based on sunflower or canola oils to increase omega-3 dietary intake. Data is collected quarterly until the infant is 1 year old and then half yearly until age 5 years. Questionnaires are used ti, collect respiratory illness history and information about diet and home environment. Dust is collected from the child's bed and bedroom and playroom floors. Blinded assessments are conducted at 18 months, 3 years, and 5 years. Skin prick tests to common allergens, blood tests, and detailed illness, medication use, and vaccination histories are collected. Primary outcomes will be the development of allergic sensitization and the presence and severity of asthma. This study is designed to measure the effectiveness of allergen reduction and dietary supplementation, both separately and in combination, for the primary prevention of atopy and asthma. The results of this study may have important implications for public health policies to reduce the incidence of childhood asthma. (C) Elsevier Science Inc. 2001.	42	84	2001	22	10.1016/S0197-2456(01)00112-X	Research & Experimental Medicine; Pharmacology & Pharmacy
Exhaled nitric oxide: The effects of age, gender and body size. Since little is known of the effects of age, gender, and body size on exhaled nitric oxide (NO) production, we have conducted a prospective study to examine these factors in a healthy nonsmoking women (mean age +/- SD 47.7 +/- 15.8, range 20-79 years). Exhaled NO was measured by an automatic chemiluminescence analyzer (Sievers NO Analyser 280) at steady expiration. Men had significantly higher exhaled NO levels than women (p = 0.001). Although exhaled NO levels did not correlate with age (r = 0.12, p = 0.17), it correlated significantly with height (r = 0.23,p = 0.02), weight (r = 0.34,p < 0.001), body mass index (r = 0.25,p = 0.009), and body surface area (r = 0.42,p < 0.001) for the entire cohort. After making adjustment for age, height, weight, body mass index, and body surface area, exhaled NO levels were still significantly higher for men than for women (p = 0.004). Our data, therefore, could help explain the discrepancy in results of previous studies on exhaled NO production, which had not taken these parameters into account. Our findings should help researchers design future studies on evaluation of exhaled NO levels.. exhaled nitric oxide| aging| gender| body mass index| body surface area|obstructive pulmonary-disease| cystic-fibrosis| air| children| bronchiectasis| markers| asthma| lungs| nasal| no.	MAR-APR-2001	exhaled nitric oxide| aging| gender| body mass index| body surface area|obstructive pulmonary-disease| cystic-fibrosis| air| children| bronchiectasis| markers| asthma| lungs| nasal| no	Tsang, KW; Ip, SK; Leung, R; Tipoe, GL; Chan, SL; Shum, IH; Ip, MS; Yan, C; Fung, PC; Chan-Yeung, M; Lam, W	Exhaled nitric oxide: The effects of age, gender and body size		LUNG	exhaled nitric oxide; aging; gender; body mass index; body surface area	OBSTRUCTIVE PULMONARY-DISEASE; CYSTIC-FIBROSIS; AIR; CHILDREN; BRONCHIECTASIS; MARKERS; ASTHMA; LUNGS; NASAL; NO	Since little is known of the effects of age, gender, and body size on exhaled nitric oxide (NO) production, we have conducted a prospective study to examine these factors in a healthy nonsmoking women (mean age +/- SD 47.7 +/- 15.8, range 20-79 years). Exhaled NO was measured by an automatic chemiluminescence analyzer (Sievers NO Analyser 280) at steady expiration. Men had significantly higher exhaled NO levels than women (p = 0.001). Although exhaled NO levels did not correlate with age (r = 0.12, p = 0.17), it correlated significantly with height (r = 0.23,p = 0.02), weight (r = 0.34,p < 0.001), body mass index (r = 0.25,p = 0.009), and body surface area (r = 0.42,p < 0.001) for the entire cohort. After making adjustment for age, height, weight, body mass index, and body surface area, exhaled NO levels were still significantly higher for men than for women (p = 0.004). Our data, therefore, could help explain the discrepancy in results of previous studies on exhaled NO production, which had not taken these parameters into account. Our findings should help researchers design future studies on evaluation of exhaled NO levels.	30	84	2001	9	10.1007/s004080000050	Respiratory System
Inducible nitric oxide synthase inhibitors suppress airway inflammation in mice through down-regulation of chemokine expression. Growing evidence demonstrates that inducible NO synthase (iNOS) is induced in the airways of asthmatic patients. However, the precise role of NO in the lung inflammation is unknown. This study investigated the effect of both selective and nonselective iNOS inhibitors in an allergen-driven murine lung inflammation model. OVA challenge resulted in an accumulation of eosinophils and neutrophils in the airways. Expression of iNOS immunostaining in lung sections together with an increase in calcium-independent NOS activity in lung homogenates was also observed after OVA challenge. Treatment with iNOS inhibitors from the day of challenge to the day of sacrifice resulted in an inhibition of the inflammatory cell influx together with a down-regulation of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 production. In contrast, eosinophilic and neutrophilic inhibition was not observed with treatment during the sensitization. Both treatments induced an increased production of Th2-type cytokines (IL-4 and IL-5) with a concomitant decrease in production of Thl-type cytokine (IFN-gamma). In vitro exposure of primary cultures of murine lung fibroblasts to a NO donor, hydroxylamine, induced a dose-dependent release of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1. Our results suggest that lung inflammation after allergen challenge in mice is partially dependent on NO produced mainly by iNOS. NO appears to increase lung chemokine expression and, thereby, to facilitate influx of inflammatory cells into the airways.. cell-adhesion molecule-1| lung epithelial-cells| in-vitro| gene-expression| rat lung| asthmatic-patients| murine model| exhaled air| modulation| induction.	AUG 1-2000	cell-adhesion molecule-1| lung epithelial-cells| in-vitro| gene-expression| rat lung| asthmatic-patients| murine model| exhaled air| modulation| induction	Trifilieff, A; Fujitani, Y; Mentz, F; Dugas, B; Fuentes, M; Bertrand, C	Inducible nitric oxide synthase inhibitors suppress airway inflammation in mice through down-regulation of chemokine expression		JOURNAL OF IMMUNOLOGY		CELL-ADHESION MOLECULE-1; LUNG EPITHELIAL-CELLS; IN-VITRO; GENE-EXPRESSION; RAT LUNG; ASTHMATIC-PATIENTS; MURINE MODEL; EXHALED AIR; MODULATION; INDUCTION	Growing evidence demonstrates that inducible NO synthase (iNOS) is induced in the airways of asthmatic patients. However, the precise role of NO in the lung inflammation is unknown. This study investigated the effect of both selective and nonselective iNOS inhibitors in an allergen-driven murine lung inflammation model. OVA challenge resulted in an accumulation of eosinophils and neutrophils in the airways. Expression of iNOS immunostaining in lung sections together with an increase in calcium-independent NOS activity in lung homogenates was also observed after OVA challenge. Treatment with iNOS inhibitors from the day of challenge to the day of sacrifice resulted in an inhibition of the inflammatory cell influx together with a down-regulation of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 production. In contrast, eosinophilic and neutrophilic inhibition was not observed with treatment during the sensitization. Both treatments induced an increased production of Th2-type cytokines (IL-4 and IL-5) with a concomitant decrease in production of Thl-type cytokine (IFN-gamma). In vitro exposure of primary cultures of murine lung fibroblasts to a NO donor, hydroxylamine, induced a dose-dependent release of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1. Our results suggest that lung inflammation after allergen challenge in mice is partially dependent on NO produced mainly by iNOS. NO appears to increase lung chemokine expression and, thereby, to facilitate influx of inflammatory cells into the airways.	53	84	2000	8		Immunology
Asthma and Latino cultures: Different prevalence reported among groups sharing the same environment. Objectives. This 1999 study measured asthma prevalence among Latinos of different cultural traditions who live on the same streets and in the same buildings. Methods. Health promoters from El Puente in North Brooklyn, New York City, surveyed 3015 people in 946 households, asking standard asthma prevalence questions. Results. Some 46%, of households identified themselves as Dominican, 42% as Puerto Rican, 6% as other Latino, and 6% as other. Reported asthma period prevalence was 5.3% (93 of 1749) among Dominicans and other Latinos, compared with 13.2% (147 of 1115)among Puerto Ricans (odds ratio = 0.37; 95% confidence interval = 0.28, 0.49), a difference not explained by location (cluster or building), household size, use of home remedies, educational attainment, or country where education was completed. Differences were least detectable among 13- to 24-year-olds of both sexes and sharpest among women aged 45 years and older and girls from birth to 12 years. Conclusions, Further research oil gene-environment interactions is needed among Puerto Ricans and Dominicans, but asthma's associations with low income and unhealthy environment, which more recent immigrants seem better able to withstand, should not be overlooked.. puerto-rican children| new-york-city| mexican-american| health| alpha-1-antitrypsin| variants| risk.	JUN-2000	puerto-rican children| new-york-city| mexican-american| health| alpha-1-antitrypsin| variants| risk	Ledogar, RJ; Penchaszadeh, A; Garden, CCI; Acosta, LG	Asthma and Latino cultures: Different prevalence reported among groups sharing the same environment		AMERICAN JOURNAL OF PUBLIC HEALTH		PUERTO-RICAN CHILDREN; NEW-YORK-CITY; MEXICAN-AMERICAN; HEALTH; ALPHA-1-ANTITRYPSIN; VARIANTS; RISK	Objectives. This 1999 study measured asthma prevalence among Latinos of different cultural traditions who live on the same streets and in the same buildings. Methods. Health promoters from El Puente in North Brooklyn, New York City, surveyed 3015 people in 946 households, asking standard asthma prevalence questions. Results. Some 46%, of households identified themselves as Dominican, 42% as Puerto Rican, 6% as other Latino, and 6% as other. Reported asthma period prevalence was 5.3% (93 of 1749) among Dominicans and other Latinos, compared with 13.2% (147 of 1115)among Puerto Ricans (odds ratio = 0.37; 95% confidence interval = 0.28, 0.49), a difference not explained by location (cluster or building), household size, use of home remedies, educational attainment, or country where education was completed. Differences were least detectable among 13- to 24-year-olds of both sexes and sharpest among women aged 45 years and older and girls from birth to 12 years. Conclusions, Further research oil gene-environment interactions is needed among Puerto Ricans and Dominicans, but asthma's associations with low income and unhealthy environment, which more recent immigrants seem better able to withstand, should not be overlooked.	20	84	2000	7	10.2105/AJPH.90.6.929	Public, Environmental & Occupational Health
Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-gamma and IL-4. Background: Chronic rhinosinusitis (CRS) is a common disease with still unclear pathophysiologic mechanisms. Epithelial tight junctions (TJs) have been shown to be involved in different chronic disorders, including bronchial asthma, inflammatory bowel diseases, and skin disorders. The regulation of epithelial barrier function and TJ expression has not been extensively studied in patients with CRS and in the paranasal sinus epithelium thus far. Objective: We sought to elucidate the TJ expression pattern in the epithelium of the sinonasal mucosa and its regulation in patients with CRS. Methods: Trans-tissue resistance was measured in biopsy specimens from healthy control subjects and patients with CRS with and without nasal polyps. TJ protein expression was determined by using immunofluorescence, Western blotting, and real-time PCR. Primary epithelial cell cultures from patients with CRS and control subjects were used in air-liquid interface (ALI) cultures for the measurement of transepithelial resistance (TER) and TJ expression. The effect of IFN-gamma, IL-4, and IL-17 on ALI cultures was assessed. Results: A decreased trans-tissue resistance was found in biopsy specimens from patients with CRS with nasal polyps along with an irregular, patchy, and decreased expression of the TJ molecules occludin and zonula occludens 1. TER was reduced in ALI cultures from patients with CRS with nasal polyps. The cytokines IFN-gamma and IL-4 decreased TER, whereas IL-17 did not have any influence on epithelial integrity. Conclusion: A defective epithelial barrier was found in patients with CRS with nasal polyps along with a decreased expression of TJ proteins. The disruption of epithelial integrity by IFN-gamma and IL-4 in vitro indicates a possible role for these proinflammatory cytokines in the pathogenesis of patients with CRS. (J Allergy Clin Immunol 2012;130:1087-96.). chronic rhinosinusitis| chronic sinusitis| tight junctions| occludin| claudin| zonula occludens| regulation| cytokines| leaky epithelium|human airway epithelia| nasal polyposis| chronic sinusitis| cells| expression| diseases| asthma| differentiation| epidemiology| inflammation.	NOV-2012	chronic rhinosinusitis| chronic sinusitis| tight junctions| occludin| claudin| zonula occludens| regulation| cytokines| leaky epithelium|human airway epithelia| nasal polyposis| chronic sinusitis| cells| expression| diseases| asthma| differentiation| epidemiology| inflammation	Soyka, MB; Wawrzyniak, P; Eiwegger, T; Holzmann, D; Treis, A; Wanke, K; Kast, JI; Akdis, CA	Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-gamma and IL-4		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Chronic rhinosinusitis; chronic sinusitis; tight junctions; occludin; claudin; zonula occludens; regulation; cytokines; leaky epithelium	HUMAN AIRWAY EPITHELIA; NASAL POLYPOSIS; CHRONIC SINUSITIS; CELLS; EXPRESSION; DISEASES; ASTHMA; DIFFERENTIATION; EPIDEMIOLOGY; INFLAMMATION	Background: Chronic rhinosinusitis (CRS) is a common disease with still unclear pathophysiologic mechanisms. Epithelial tight junctions (TJs) have been shown to be involved in different chronic disorders, including bronchial asthma, inflammatory bowel diseases, and skin disorders. The regulation of epithelial barrier function and TJ expression has not been extensively studied in patients with CRS and in the paranasal sinus epithelium thus far. Objective: We sought to elucidate the TJ expression pattern in the epithelium of the sinonasal mucosa and its regulation in patients with CRS. Methods: Trans-tissue resistance was measured in biopsy specimens from healthy control subjects and patients with CRS with and without nasal polyps. TJ protein expression was determined by using immunofluorescence, Western blotting, and real-time PCR. Primary epithelial cell cultures from patients with CRS and control subjects were used in air-liquid interface (ALI) cultures for the measurement of transepithelial resistance (TER) and TJ expression. The effect of IFN-gamma, IL-4, and IL-17 on ALI cultures was assessed. Results: A decreased trans-tissue resistance was found in biopsy specimens from patients with CRS with nasal polyps along with an irregular, patchy, and decreased expression of the TJ molecules occludin and zonula occludens 1. TER was reduced in ALI cultures from patients with CRS with nasal polyps. The cytokines IFN-gamma and IL-4 decreased TER, whereas IL-17 did not have any influence on epithelial integrity. Conclusion: A defective epithelial barrier was found in patients with CRS with nasal polyps along with a decreased expression of TJ proteins. The disruption of epithelial integrity by IFN-gamma and IL-4 in vitro indicates a possible role for these proinflammatory cytokines in the pathogenesis of patients with CRS. (J Allergy Clin Immunol 2012;130:1087-96.)	49	83	2012	20	10.1016/j.jaci.2012.05.052	Allergy; Immunology
Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects Current knowledge assembled at an international workshop at BfR, Germany. Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.. contact allergy| dermatitis| epidemiology| molecular mechanisms| regulatory aspects|lymph-node assay| occupational skin-disease| human dendritic cells| receptor accessory protein| pig maximization test| necrosis-factor-alpha| n-acetyltransferase 1| toll-like receptor| effector t-cells| test h-clat.	MAR-2012	contact allergy| dermatitis| epidemiology| molecular mechanisms| regulatory aspects|lymph-node assay| occupational skin-disease| human dendritic cells| receptor accessory protein| pig maximization test| necrosis-factor-alpha| n-acetyltransferase 1| toll-like receptor| effector t-cells| test h-clat	Peiser, M; Tralau, T; Heidler, J; Api, AM; Arts, JHE; Basketter, DA; English, J; Diepgen, TL; Fuhlbrigge, RC; Gaspari, AA; Johansen, JD; Karlberg, AT; Kimber, I; Lepoittevin, JP; Liebsch, M; Maibach, HI; Martin, SF; Merk, HF; Platzek, T; Rustemeyer, T; Schnuch, A; Vandebriel, RJ; White, IR; Luch, A	Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects Current knowledge assembled at an international workshop at BfR, Germany		CELLULAR AND MOLECULAR LIFE SCIENCES	Contact allergy; Dermatitis; Epidemiology; Molecular mechanisms; Regulatory aspects	LYMPH-NODE ASSAY; OCCUPATIONAL SKIN-DISEASE; HUMAN DENDRITIC CELLS; RECEPTOR ACCESSORY PROTEIN; PIG MAXIMIZATION TEST; NECROSIS-FACTOR-ALPHA; N-ACETYLTRANSFERASE 1; TOLL-LIKE RECEPTOR; EFFECTOR T-CELLS; TEST H-CLAT	Contact allergies are complex diseases, and one of the important challenges for public health and immunology. The German 'Federal Institute for Risk Assessment' hosted an 'International Workshop on Contact Dermatitis'. The scope of the workshop was to discuss new discoveries and developments in the field of contact dermatitis. This included the epidemiology and molecular biology of contact allergy, as well as the development of new in vitro methods. Furthermore, it considered regulatory aspects aiming to reduce exposure to contact sensitisers. An estimated 15-20% of the general population suffers from contact allergy. Workplace exposure, age, sex, use of consumer products and genetic predispositions were identified as the most important risk factors. Research highlights included: advances in understanding of immune responses to contact sensitisers, the importance of autoxidation or enzyme-mediated oxidation for the activation of chemicals, the mechanisms through which hapten-protein conjugates are formed and the development of novel in vitro strategies for the identification of skin-sensitising chemicals. Dendritic cell cultures and structure-activity relationships are being developed to identify potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed.	210	83	2012	19	10.1007/s00018-011-0846-8	Biochemistry & Molecular Biology; Cell Biology
p38 Mitogen-Activated Protein Kinase Pathways in Asthma and COPD. The mitogen-activated protein kinase (MAPK) family includes the p38 kinases, which consist of highly conserved proline-directed serine-threonine protein kinases that are activated in response to inflammatory signals. Of the four isoforms, p38 alpha is the most abundant in inflammatory cells and has been the most studied through mainly the availability of small molecule inhibitors. The p38 substrates include transcription factors; other protein kinases, which in turn phosphorylate transcription factors; cytoskeletal proteins and translational components; and other enzymes. Both asthma and COPD are characterized by chronic airflow obstruction, airway and lung remodeling, and chronic inflammation. p38 is involved in the inflammatory responses induced by cigarette smoke exposure, endotoxin, and oxidative stress through activation and release of proinflammatory cytokines/chemokines, posttranslational regulation of these genes, and activation of inflammatory cell migration. Inhibition of p38 MAPK prevented allergen-induced pulmonary eosinophilia, mucus hypersecretion, and airway hyperresponsiveness, effects that may partly result from p38 activation on eosinophil apoptosis and on airway smooth muscle cell production of cytokines/chemokines. In addition, p38 regulates the augmented contractile response induced by oxidative stress. The activation of p38 observed in epithelial cells and macrophages also may underlie corticosteroid insensitivity of severe asthma and COPD. Therefore, p38 inhibitors present a potential attractive treatment of these conditions. Second-generation p38 inhibitors have been disappointing in the treatment of rheumatoid arthritis. In two 6-week studies in patients with COPD, the results were encouraging. Side effects such as liver toxicity remain a possibility, and whether the beneficial effects of p38 inhibitors are clinically significant and sustained need to be determined. CHEST 2011; 139(6):1470-1479. airway smooth-muscle| nf-kappa-b| relative corticosteroid insensitivity| obstructive pulmonary-disease| human alveolar macrophages| heat-shock-protein| map-kinase| glucocorticoid-receptor| cell-migration| cytokine release.	JUN-2011	airway smooth-muscle| nf-kappa-b| relative corticosteroid insensitivity| obstructive pulmonary-disease| human alveolar macrophages| heat-shock-protein| map-kinase| glucocorticoid-receptor| cell-migration| cytokine release	Chung, KF	p38 Mitogen-Activated Protein Kinase Pathways in Asthma and COPD		CHEST		AIRWAY SMOOTH-MUSCLE; NF-KAPPA-B; RELATIVE CORTICOSTEROID INSENSITIVITY; OBSTRUCTIVE PULMONARY-DISEASE; HUMAN ALVEOLAR MACROPHAGES; HEAT-SHOCK-PROTEIN; MAP-KINASE; GLUCOCORTICOID-RECEPTOR; CELL-MIGRATION; CYTOKINE RELEASE	The mitogen-activated protein kinase (MAPK) family includes the p38 kinases, which consist of highly conserved proline-directed serine-threonine protein kinases that are activated in response to inflammatory signals. Of the four isoforms, p38 alpha is the most abundant in inflammatory cells and has been the most studied through mainly the availability of small molecule inhibitors. The p38 substrates include transcription factors; other protein kinases, which in turn phosphorylate transcription factors; cytoskeletal proteins and translational components; and other enzymes. Both asthma and COPD are characterized by chronic airflow obstruction, airway and lung remodeling, and chronic inflammation. p38 is involved in the inflammatory responses induced by cigarette smoke exposure, endotoxin, and oxidative stress through activation and release of proinflammatory cytokines/chemokines, posttranslational regulation of these genes, and activation of inflammatory cell migration. Inhibition of p38 MAPK prevented allergen-induced pulmonary eosinophilia, mucus hypersecretion, and airway hyperresponsiveness, effects that may partly result from p38 activation on eosinophil apoptosis and on airway smooth muscle cell production of cytokines/chemokines. In addition, p38 regulates the augmented contractile response induced by oxidative stress. The activation of p38 observed in epithelial cells and macrophages also may underlie corticosteroid insensitivity of severe asthma and COPD. Therefore, p38 inhibitors present a potential attractive treatment of these conditions. Second-generation p38 inhibitors have been disappointing in the treatment of rheumatoid arthritis. In two 6-week studies in patients with COPD, the results were encouraging. Side effects such as liver toxicity remain a possibility, and whether the beneficial effects of p38 inhibitors are clinically significant and sustained need to be determined. CHEST 2011; 139(6):1470-1479	94	83	2011	10	10.1378/chest.10-1914	General & Internal Medicine; Respiratory System
Understanding The Cumulative Impacts Of Inequalities In Environmental Health: Implications For Policy. Racial or ethnic minority groups and low-income communities have poorer health outcomes than others. They are more frequently exposed to multiple environmental hazards and social stressors, including poverty, poor housing quality, and social inequality. Researchers are grappling with how best to characterize the cumulative effects of these hazards and stressors in order to help regulators and decision makers craft more-effective policies to address health and environmental disparities. In this article we synthesize the existing scientific evidence regarding the cumulative health implications of higher rates of exposure to environmental hazards, along with individual biological susceptibility and social vulnerability. We conclude that current environmental policy, which is focused narrowly on pollutants and their sources, should be broadened to take into account the cumulative impact of exposures and vulnerabilities encountered by people who live in neighborhoods consisting largely of racial or ethnic minorities or people of low socioeconomic status.. self-rated health| adverse birth outcomes| ambient air-pollution| united-states| cardiovascular-disease| childhood asthma| hazardous-waste| risk-assessment| older-adults| disparities.	MAY-2011	self-rated health| adverse birth outcomes| ambient air-pollution| united-states| cardiovascular-disease| childhood asthma| hazardous-waste| risk-assessment| older-adults| disparities	Morello-Frosch, R; Zuk, M; Jerrett, M; Shamasunder, B; Kyle, AD	Understanding The Cumulative Impacts Of Inequalities In Environmental Health: Implications For Policy		HEALTH AFFAIRS		SELF-RATED HEALTH; ADVERSE BIRTH OUTCOMES; AMBIENT AIR-POLLUTION; UNITED-STATES; CARDIOVASCULAR-DISEASE; CHILDHOOD ASTHMA; HAZARDOUS-WASTE; RISK-ASSESSMENT; OLDER-ADULTS; DISPARITIES	Racial or ethnic minority groups and low-income communities have poorer health outcomes than others. They are more frequently exposed to multiple environmental hazards and social stressors, including poverty, poor housing quality, and social inequality. Researchers are grappling with how best to characterize the cumulative effects of these hazards and stressors in order to help regulators and decision makers craft more-effective policies to address health and environmental disparities. In this article we synthesize the existing scientific evidence regarding the cumulative health implications of higher rates of exposure to environmental hazards, along with individual biological susceptibility and social vulnerability. We conclude that current environmental policy, which is focused narrowly on pollutants and their sources, should be broadened to take into account the cumulative impact of exposures and vulnerabilities encountered by people who live in neighborhoods consisting largely of racial or ethnic minorities or people of low socioeconomic status.	77	83	2011	9	10.1377/hlthaff.2011.0153	Health Care Sciences & Services
Million trees Los Angeles canopy cover and benefit assessment. The Million Trees LA initiative intends to improve Los Angeles's environment through planting and stewardship of 1 million trees. The purpose of this study was to measure Los Angeles's existing tree canopy cover (TCC), determine if space exists for 1 million additional trees, and estimate future benefits from the planting. High-resolution QuickBird remote sensing data, aerial photographs, and geographic information systems were used to classify land cover types, measure TCC, and identify potential tree planting sites. Benefits were forecast for planting of 1 million trees between 2006 and 2010, and their growth and mortality were projected until 2040. Two scenarios reflected low (17%) and high (56%) mortality rates. Numerical models were used with geographic data and tree size information for coastal and inland climate zones to calculate annual benefits and their monetary value. Los Angeles's existing TCC was 21%, and ranged from 7 to 37% by council district. There was potential to add 2.5 million additional trees to the existing population of approximately 10.8 million, but only 1.3 million of the potential tree sites are deemed realistic to plant. Benefits for the 1-million-tree planting for the 35-year period were $1.33 billion and $1.95 billion for the high- and low-mortality scenarios, respectively. Average annual benefits were $38 and $56 per tree planted. Eighty-one percent of total benefits were aesthetic/other, 8% were stormwater runoff reduction, 6% energy savings, 4% air quality improvement, and less than 1% atmospheric carbon reduction. Published by Elsevier B.V.. ecosystem services| urban forestry| tree canopy cover| tree benefits|urban forest| california| vegetation| health| asthma| costs| areas.	JAN 30-2011	ecosystem services| urban forestry| tree canopy cover| tree benefits|urban forest| california| vegetation| health| asthma| costs| areas	McPherson, EG; Simpson, JR; Xiao, QF; Wu, CX	Million trees Los Angeles canopy cover and benefit assessment		LANDSCAPE AND URBAN PLANNING	Ecosystem services; Urban forestry; Tree canopy cover; Tree benefits	URBAN FOREST; CALIFORNIA; VEGETATION; HEALTH; ASTHMA; COSTS; AREAS	The Million Trees LA initiative intends to improve Los Angeles's environment through planting and stewardship of 1 million trees. The purpose of this study was to measure Los Angeles's existing tree canopy cover (TCC), determine if space exists for 1 million additional trees, and estimate future benefits from the planting. High-resolution QuickBird remote sensing data, aerial photographs, and geographic information systems were used to classify land cover types, measure TCC, and identify potential tree planting sites. Benefits were forecast for planting of 1 million trees between 2006 and 2010, and their growth and mortality were projected until 2040. Two scenarios reflected low (17%) and high (56%) mortality rates. Numerical models were used with geographic data and tree size information for coastal and inland climate zones to calculate annual benefits and their monetary value. Los Angeles's existing TCC was 21%, and ranged from 7 to 37% by council district. There was potential to add 2.5 million additional trees to the existing population of approximately 10.8 million, but only 1.3 million of the potential tree sites are deemed realistic to plant. Benefits for the 1-million-tree planting for the 35-year period were $1.33 billion and $1.95 billion for the high- and low-mortality scenarios, respectively. Average annual benefits were $38 and $56 per tree planted. Eighty-one percent of total benefits were aesthetic/other, 8% were stormwater runoff reduction, 6% energy savings, 4% air quality improvement, and less than 1% atmospheric carbon reduction. Published by Elsevier B.V.	57	83	2011	11	10.1016/j.landurbplan.2010.08.011	Environmental Sciences & Ecology; Geography; Physical Geography; Urban Studies
"The immune effects of naturally occurring and synthetic nanoparticles. Ultrafine particles and engineered nanoparticles have unique aerodynamic and biochemical properties that affect the immune system and human health in ways that are different from or exceed those seen with gases or larger particulates. These effects result from a unique set of physical characteristics and surface moieties, which generate an ability of UFPs to enter tissues and cells, interact with proteins and DNA at a molecular level and directly and indirectly modulate the immune system by novel mechanisms. In recent years, a new field known as nanotechnology has impacted multiple industries by taking advantage of the special qualities of these small ""atomic-sized"" particles. Nanomedicine has already opened up a new avenue of research in cancer therapy, drug delivery and immune regulation. While the benefits of this new science to human civilization are seemingly immeasurable, it is also important to appreciate that these particles can also lead to harmful effects on human health. In vitro and animal studies are showing that nanoparticles and UFPs are capable of activating proinflammatory cytokines, chemokines and adhesion molecules, with recruitment of inflammatory cells including basophils, macrophages, dendritic cells, T cells, neutrophils and eosinophils. These changes may have an impact on immune defense, but also on the Th1/Th2 balance, and even on non-immunologic function. Resulting immune system derangement can lead to increases in incidence of autoimmune, allergic and even neoplastic diseases. Cardiorespiratory effects have been observed to occur in humans. Much further research is needed to establish safe exposure levels for this important new class of particulates. (C) 2009 Elsevier Ltd. All rights reserved.. ultrafine particles| nanoparticles| nanotechnology| air pollution| climate change| diesel exhaust particles| asthma| anthropogenic| environmental tobacco smoke| particulate matter| pm(2.5)| pm(10)| oxidative stress| adjuvants| reactive oxygen species| carbon nanotubes| autoimmunity|diesel exhaust particles| inhaled ultrafine particles| collagen-induced arthritis| blood mononuclear-cells| oxidative stress| air-pollution| particulate matter| titanium-dioxide| in-vivo| epithelial-cells."	MAY-2010	ultrafine particles| nanoparticles| nanotechnology| air pollution| climate change| diesel exhaust particles| asthma| anthropogenic| environmental tobacco smoke| particulate matter| pm(2.5)| pm(10)| oxidative stress| adjuvants| reactive oxygen species| carbon nanotubes| autoimmunity|diesel exhaust particles| inhaled ultrafine particles| collagen-induced arthritis| blood mononuclear-cells| oxidative stress| air-pollution| particulate matter| titanium-dioxide| in-vivo| epithelial-cells	Chang, C	The immune effects of naturally occurring and synthetic nanoparticles		JOURNAL OF AUTOIMMUNITY	Ultrafine particles; Nanoparticles; Nanotechnology; Air pollution; Climate change; Diesel exhaust particles; Asthma; Anthropogenic; Environmental tobacco smoke; Particulate matter; PM(2.5); PM(10); Oxidative stress; Adjuvants; Reactive oxygen species; Carbon nanotubes; Autoimmunity	DIESEL EXHAUST PARTICLES; INHALED ULTRAFINE PARTICLES; COLLAGEN-INDUCED ARTHRITIS; BLOOD MONONUCLEAR-CELLS; OXIDATIVE STRESS; AIR-POLLUTION; PARTICULATE MATTER; TITANIUM-DIOXIDE; IN-VIVO; EPITHELIAL-CELLS	"Ultrafine particles and engineered nanoparticles have unique aerodynamic and biochemical properties that affect the immune system and human health in ways that are different from or exceed those seen with gases or larger particulates. These effects result from a unique set of physical characteristics and surface moieties, which generate an ability of UFPs to enter tissues and cells, interact with proteins and DNA at a molecular level and directly and indirectly modulate the immune system by novel mechanisms. In recent years, a new field known as nanotechnology has impacted multiple industries by taking advantage of the special qualities of these small ""atomic-sized"" particles. Nanomedicine has already opened up a new avenue of research in cancer therapy, drug delivery and immune regulation. While the benefits of this new science to human civilization are seemingly immeasurable, it is also important to appreciate that these particles can also lead to harmful effects on human health. In vitro and animal studies are showing that nanoparticles and UFPs are capable of activating proinflammatory cytokines, chemokines and adhesion molecules, with recruitment of inflammatory cells including basophils, macrophages, dendritic cells, T cells, neutrophils and eosinophils. These changes may have an impact on immune defense, but also on the Th1/Th2 balance, and even on non-immunologic function. Resulting immune system derangement can lead to increases in incidence of autoimmune, allergic and even neoplastic diseases. Cardiorespiratory effects have been observed to occur in humans. Much further research is needed to establish safe exposure levels for this important new class of particulates. (C) 2009 Elsevier Ltd. All rights reserved."	113	83	2010	13	10.1016/j.jaut.2009.11.009	Immunology
5-Lipoxygenase inhibitors: a review of recent developments and patents. Importance to the field: Leukotrienes (LTs) are pivotal lipid mediators of inflammation and allergy and results from recent studies also suggest roles of LTs in cardiovascular diseases, cancer and osteoporosis. 5-Lipoxygenase (5-LO) catalyzes the first step in the biosynthesis of LTs from arachidonic acid, and based on the multiple potent pathophysiological actions of LTs, the pharmacological intervention with 5-LO is a challenge in the development of therapeutics. Areas covered in this review: We first summarize the biochemical regulation of 5-LO and the general pharmacological concepts in 5-LO inhibition by currently available compounds, and subsequently we report recent developments deduced from recent scientific publications and patents. What the reader will gain: A comprehensive overview about the different molecular pharmacological strategies to inhibit 5-LO and the most successful previous 5-LO inhibitors. The review also gives insights into novel concepts, for example, dual prostaglandin/LT synthesis inhibition and reveals novel compounds patented or developed within the past 5 years. Take home message: Despite the increasing therapeutic indications of anti-LT therapy, the progress in the development of novel 5-LO inhibitors is moderate. However, novel molecular concepts in the intervention with LT biosynthesis seem promising.. arachidonic acid| asthma| inflammation| inhibitors| leukotriene| 5-lipoxygenase|prostaglandin e-2 synthase-1| cytosolic phospholipase a(2)| pharmacophore biological evaluation| human polymorphonuclear leukocytes| coactosin-like protein| dual inhibitors| leukotriene b-4| antiinflammatory activity| arachidonate 5-lipoxygenase| pharmacological profile.	MAR-2010	arachidonic acid| asthma| inflammation| inhibitors| leukotriene| 5-lipoxygenase|prostaglandin e-2 synthase-1| cytosolic phospholipase a(2)| pharmacophore biological evaluation| human polymorphonuclear leukocytes| coactosin-like protein| dual inhibitors| leukotriene b-4| antiinflammatory activity| arachidonate 5-lipoxygenase| pharmacological profile	Pergola, C; Werz, O	5-Lipoxygenase inhibitors: a review of recent developments and patents		EXPERT OPINION ON THERAPEUTIC PATENTS	arachidonic acid; asthma; inflammation; inhibitors; leukotriene; 5-lipoxygenase	PROSTAGLANDIN E-2 SYNTHASE-1; CYTOSOLIC PHOSPHOLIPASE A(2); PHARMACOPHORE BIOLOGICAL EVALUATION; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; COACTOSIN-LIKE PROTEIN; DUAL INHIBITORS; LEUKOTRIENE B-4; ANTIINFLAMMATORY ACTIVITY; ARACHIDONATE 5-LIPOXYGENASE; PHARMACOLOGICAL PROFILE	Importance to the field: Leukotrienes (LTs) are pivotal lipid mediators of inflammation and allergy and results from recent studies also suggest roles of LTs in cardiovascular diseases, cancer and osteoporosis. 5-Lipoxygenase (5-LO) catalyzes the first step in the biosynthesis of LTs from arachidonic acid, and based on the multiple potent pathophysiological actions of LTs, the pharmacological intervention with 5-LO is a challenge in the development of therapeutics. Areas covered in this review: We first summarize the biochemical regulation of 5-LO and the general pharmacological concepts in 5-LO inhibition by currently available compounds, and subsequently we report recent developments deduced from recent scientific publications and patents. What the reader will gain: A comprehensive overview about the different molecular pharmacological strategies to inhibit 5-LO and the most successful previous 5-LO inhibitors. The review also gives insights into novel concepts, for example, dual prostaglandin/LT synthesis inhibition and reveals novel compounds patented or developed within the past 5 years. Take home message: Despite the increasing therapeutic indications of anti-LT therapy, the progress in the development of novel 5-LO inhibitors is moderate. However, novel molecular concepts in the intervention with LT biosynthesis seem promising.	126	83	2010	21	10.1517/13543771003602012	Pharmacology & Pharmacy
Silent mysteries: epigenetic paradigms could hold the key to conquering the epidemic of allergy and immune disease. P>Epigenetic mechanisms provide new insights into how environmental changes may mediate the increasing propensity for complex immune diseases such as allergic disease. There is now strong evidence that early environmental exposures play a key role in activating or silencing genes by altering DNA and histone methylation, histone acetylation and chromatin structure. These modifications determine the degree of DNA compaction and accessibility for gene transcription, altering gene expression, phenotype and disease susceptibility. While there is already evidence that a number of early environmental exposures are associated with an increased risk of allergic disease, several new studies indicate in utero microbial and dietary exposures can modify gene expression and allergic disease propensity through epigenetic modification. This review explores the evidence that immune development is under clear epigenetic regulation, including the pattern of T helper (Th)1 and Th2 cell differentiation, regulatory T cell differentiation, and more recently, Th17 development. It also considers the mechanisms of epigenetic regulation and early immune defects in allergy prone neonates. The inherent plasticity conferred by epigenetic mechanisms clearly also provides opportunities for environmental strategies that can re-programme gene expression for disease prevention. Identifying genes that are differentially silenced or activated in relation to subsequent disease will not only assist in identifying causal pathways, but may also help identify the contributing environmental factors.. acetylation| allergic disease| epigenetics| methylation| susceptibility|ifn-gamma promoter| dna methylation changes| t-cell differentiation| foxp3 gene-expression| airway inflammation| in-utero| histone deacetylases| th2 differentiation| lineage commitment| cytokine responses.	JAN-2010	acetylation| allergic disease| epigenetics| methylation| susceptibility|ifn-gamma promoter| dna methylation changes| t-cell differentiation| foxp3 gene-expression| airway inflammation| in-utero| histone deacetylases| th2 differentiation| lineage commitment| cytokine responses	Martino, DJ; Prescott, SL	Silent mysteries: epigenetic paradigms could hold the key to conquering the epidemic of allergy and immune disease		ALLERGY	acetylation; allergic disease; epigenetics; methylation; susceptibility	IFN-GAMMA PROMOTER; DNA METHYLATION CHANGES; T-CELL DIFFERENTIATION; FOXP3 GENE-EXPRESSION; AIRWAY INFLAMMATION; IN-UTERO; HISTONE DEACETYLASES; TH2 DIFFERENTIATION; LINEAGE COMMITMENT; CYTOKINE RESPONSES	P>Epigenetic mechanisms provide new insights into how environmental changes may mediate the increasing propensity for complex immune diseases such as allergic disease. There is now strong evidence that early environmental exposures play a key role in activating or silencing genes by altering DNA and histone methylation, histone acetylation and chromatin structure. These modifications determine the degree of DNA compaction and accessibility for gene transcription, altering gene expression, phenotype and disease susceptibility. While there is already evidence that a number of early environmental exposures are associated with an increased risk of allergic disease, several new studies indicate in utero microbial and dietary exposures can modify gene expression and allergic disease propensity through epigenetic modification. This review explores the evidence that immune development is under clear epigenetic regulation, including the pattern of T helper (Th)1 and Th2 cell differentiation, regulatory T cell differentiation, and more recently, Th17 development. It also considers the mechanisms of epigenetic regulation and early immune defects in allergy prone neonates. The inherent plasticity conferred by epigenetic mechanisms clearly also provides opportunities for environmental strategies that can re-programme gene expression for disease prevention. Identifying genes that are differentially silenced or activated in relation to subsequent disease will not only assist in identifying causal pathways, but may also help identify the contributing environmental factors.	81	83	2010	9	10.1111/j.1398-9995.2009.02186.x	Allergy; Immunology
Mitochondrial Dysfunction Increases Allergic Airway Inflammation. The prevalence of allergies and asthma among the world's population has been steadily increasing due to environmental factors. It has been described that exposure to ozone, diesel exhaust particles, or tobacco smoke exacerbates allergic inflammation in the lungs. These environmental oxidants increase the levels of cellular reactive oxygen species (ROS) and induce mitochondrial dysfunction in the airway epithelium. In this study, we investigated the involvement of preexisting mitochondrial dysfunction in the exacerbation of allergic airway inflammation. After cellular oxidative insult induced by ragweed pollen extract (RWE) exposure, we have identified nine oxidatively damaged mitochondrial respiratory chain-complex and associated proteins. Out of these, the ubiquinol-cytochrome c reductase core II protein (UQCRC2) was found to be implicated in mitochondrial ROS generation from respiratory complex III. Mitochondrial dysfunction induced by deficiency of UQCRC2 in airway epithelium of sensitized BALB/c mice prior the RWE challenge increased the Ag-induced accumulation of eosinophils, mucin levels in the airways, and bronchial hyperresponsiveness. Deficiency of UQCRC1, another oxidative damage-sensitive complex III protein, did not significantly alter cellular ROS levels or the intensity of RWE-induced airway inflammation. These observations suggest that preexisting mitochondrial dysfunction induced by oxidant environmental pollutants is responsible for the severe symptoms in allergic airway inflammation. These data also imply that mitochondrial defects could be risk factors and may be responsible for severe allergic disorders in atopic individuals. The Journal of Immunology, 2009, 183: 5379-5387.. electron-transport chain| oxidatively damaged proteins| cytochrome bc(1) complex| gel-electrophoresis| core proteins| asthma| stress| pollen| cells| identification.	OCT 15-2009	electron-transport chain| oxidatively damaged proteins| cytochrome bc(1) complex| gel-electrophoresis| core proteins| asthma| stress| pollen| cells| identification	Aguilera-Aguirre, L; Bacsi, A; Saavedra-Molina, A; Kurosky, A; Sur, S; Boldogh, I	Mitochondrial Dysfunction Increases Allergic Airway Inflammation		JOURNAL OF IMMUNOLOGY		ELECTRON-TRANSPORT CHAIN; OXIDATIVELY DAMAGED PROTEINS; CYTOCHROME BC(1) COMPLEX; GEL-ELECTROPHORESIS; CORE PROTEINS; ASTHMA; STRESS; POLLEN; CELLS; IDENTIFICATION	The prevalence of allergies and asthma among the world's population has been steadily increasing due to environmental factors. It has been described that exposure to ozone, diesel exhaust particles, or tobacco smoke exacerbates allergic inflammation in the lungs. These environmental oxidants increase the levels of cellular reactive oxygen species (ROS) and induce mitochondrial dysfunction in the airway epithelium. In this study, we investigated the involvement of preexisting mitochondrial dysfunction in the exacerbation of allergic airway inflammation. After cellular oxidative insult induced by ragweed pollen extract (RWE) exposure, we have identified nine oxidatively damaged mitochondrial respiratory chain-complex and associated proteins. Out of these, the ubiquinol-cytochrome c reductase core II protein (UQCRC2) was found to be implicated in mitochondrial ROS generation from respiratory complex III. Mitochondrial dysfunction induced by deficiency of UQCRC2 in airway epithelium of sensitized BALB/c mice prior the RWE challenge increased the Ag-induced accumulation of eosinophils, mucin levels in the airways, and bronchial hyperresponsiveness. Deficiency of UQCRC1, another oxidative damage-sensitive complex III protein, did not significantly alter cellular ROS levels or the intensity of RWE-induced airway inflammation. These observations suggest that preexisting mitochondrial dysfunction induced by oxidant environmental pollutants is responsible for the severe symptoms in allergic airway inflammation. These data also imply that mitochondrial defects could be risk factors and may be responsible for severe allergic disorders in atopic individuals. The Journal of Immunology, 2009, 183: 5379-5387.	61	83	2009	9		Immunology
Farm exposure in utero may protect against asthma, hay fever and eczema. The aim of the present study was to assess which factors contribute to the lower prevalence of allergic diseases in farmers' children, and the importance of timing of exposure. In a cross-sectional questionnaire survey, asthma symptoms, hay fever and eczema were assessed, as well as current, early and prenatal farm-related exposures in 1,333 farmers' children and 566 reference children aged 5-17 yrs. Farmers' children had a lower incidence of asthma symptoms and eczema. Current and maternal exposure during pregnancy to animals and/or grain and hay reduced the risk of asthma symptoms, hay fever and eczema. The exposure-response association for maternal exposure was nonlinear for most outcomes. After mutual adjustment, the effects of prenatal exposure remained unchanged whereas current exposure remained protective only for asthma medication, asthma ever and hay fever. Exposure during the first 2 yrs was not associated with symptoms, after controlling for prenatal exposure. A combination of prenatal and current exposure was most strongly associated with wheeze (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.80), asthma medication (OR 0.50, 95% Cl 0.30-0.82), asthma ever (OR 0.50, 95% Cl 0.33-0.76), hay fever (OR 0.47, 95% Cl 0.30-0.73) and eczema (OR 0.46, 95% Cl 0.30-0.70). Prenatal exposure may contribute to the low prevalence of asthma, hay fever and eczema in farmers' children, but continued exposure may be required to maintain optimal protection.. asthma| farming| hygiene hypothesis| prenatal| timing|allergy.	SEP-2008	asthma| farming| hygiene hypothesis| prenatal| timing|allergy	Douwes, J; Cheng, S; Travier, N; Cohet, C; Niesink, A; McKenzie, J; Cunningham, C; Le Gros, G; von Mutius, E; Pearce, N	Farm exposure in utero may protect against asthma, hay fever and eczema		EUROPEAN RESPIRATORY JOURNAL	asthma; farming; hygiene hypothesis; prenatal; timing	ALLERGY	The aim of the present study was to assess which factors contribute to the lower prevalence of allergic diseases in farmers' children, and the importance of timing of exposure. In a cross-sectional questionnaire survey, asthma symptoms, hay fever and eczema were assessed, as well as current, early and prenatal farm-related exposures in 1,333 farmers' children and 566 reference children aged 5-17 yrs. Farmers' children had a lower incidence of asthma symptoms and eczema. Current and maternal exposure during pregnancy to animals and/or grain and hay reduced the risk of asthma symptoms, hay fever and eczema. The exposure-response association for maternal exposure was nonlinear for most outcomes. After mutual adjustment, the effects of prenatal exposure remained unchanged whereas current exposure remained protective only for asthma medication, asthma ever and hay fever. Exposure during the first 2 yrs was not associated with symptoms, after controlling for prenatal exposure. A combination of prenatal and current exposure was most strongly associated with wheeze (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.28-0.80), asthma medication (OR 0.50, 95% Cl 0.30-0.82), asthma ever (OR 0.50, 95% Cl 0.33-0.76), hay fever (OR 0.47, 95% Cl 0.30-0.73) and eczema (OR 0.46, 95% Cl 0.30-0.70). Prenatal exposure may contribute to the low prevalence of asthma, hay fever and eczema in farmers' children, but continued exposure may be required to maintain optimal protection.	2	83	2008	9	10.1183/09031936.00033707	Respiratory System
Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives. Background Birch pollen and pollen from related trees of the Fagales order are a major cause of allergic rhinitis, conjunctivitis, and asthma through the spring season in northern and central Europe. Objective To investigate the clinical effects of injection immunotherapy with genetically modified derivatives of major birch pollen allergen Bet v 1 on pollen-induced allergic symptoms. Methods A three-arm double-blind placebo-controlled immunotherapy study was conducted with one pre-seasonal course of treatment using two derivatives of Bet v 1, namely a recombinant Bet v 1 trimer and an equimolar mixture of two recombinant Bet v 1 fragments together representing the whole protein sequence. Analysis of local and systemic adverse events was performed for 124 patients who had received at least one dose of medication. Clinical efficacy was monitored by symptom medication scores and interval scoring in the per protocol-treated population (n=84). In addition, skin and nasal provocation responses and allergen-specific antibodies were assessed. Results There were trends towards improvement in the subjects' well-being and clinical symptoms (nasal scores), although comparisons with a placebo group did not show statistical significance in the main end-point, the combined symptom medication score. Reductions in skin and nasal sensitivity were observed for some subjects with a trend for the Bet v 1 trimer to be more effective than the fragments. Treatment induced strong IgG1 and IgG4 allergen-specific antibody responses. Local injection-site reactions were most frequent in the trimer group affecting 59.5% of patients as opposed to 37.8% and 30.6% in the fragment and placebo groups, respectively. Systemic reactions were elicited more frequently by fragments. A large proportion of adverse side-effects appeared hours following injections, and might be attributable to concurrent exposure to related pollens. Conclusion Single courses of injection immunotherapy with Bet v 1 allergen derivatives showed trends towards improved well-being and reduced reactivity to specific allergen provocation, but did not yield significant improvement in the combined symptom medication score in this study.. allergen variants| allergic rhinitis| allergy| bet v 1| birch pollen| immunotherapy| recombinant allergens|bet v 1| allergen-specific immunotherapy| quantitative ige inhibition| late asthmatic reactions| wild-type| vaccination| sensitivity| transition| population| candidates.	SEP-2008	allergen variants| allergic rhinitis| allergy| bet v 1| birch pollen| immunotherapy| recombinant allergens|bet v 1| allergen-specific immunotherapy| quantitative ige inhibition| late asthmatic reactions| wild-type| vaccination| sensitivity| transition| population| candidates	Purohit, A; Niederberger, V; Kronqvist, M; Horak, F; Gronneberg, R; Suck, R; Weber, B; Fiebig, H; van Hage, M; Pauli, G; Valenta, R; Cromwell, O	Clinical effects of immunotherapy with genetically modified recombinant birch pollen Bet v 1 derivatives		CLINICAL AND EXPERIMENTAL ALLERGY	allergen variants; allergic rhinitis; allergy; Bet v 1; birch pollen; immunotherapy; recombinant allergens	BET V 1; ALLERGEN-SPECIFIC IMMUNOTHERAPY; QUANTITATIVE IGE INHIBITION; LATE ASTHMATIC REACTIONS; WILD-TYPE; VACCINATION; SENSITIVITY; TRANSITION; POPULATION; CANDIDATES	Background Birch pollen and pollen from related trees of the Fagales order are a major cause of allergic rhinitis, conjunctivitis, and asthma through the spring season in northern and central Europe. Objective To investigate the clinical effects of injection immunotherapy with genetically modified derivatives of major birch pollen allergen Bet v 1 on pollen-induced allergic symptoms. Methods A three-arm double-blind placebo-controlled immunotherapy study was conducted with one pre-seasonal course of treatment using two derivatives of Bet v 1, namely a recombinant Bet v 1 trimer and an equimolar mixture of two recombinant Bet v 1 fragments together representing the whole protein sequence. Analysis of local and systemic adverse events was performed for 124 patients who had received at least one dose of medication. Clinical efficacy was monitored by symptom medication scores and interval scoring in the per protocol-treated population (n=84). In addition, skin and nasal provocation responses and allergen-specific antibodies were assessed. Results There were trends towards improvement in the subjects' well-being and clinical symptoms (nasal scores), although comparisons with a placebo group did not show statistical significance in the main end-point, the combined symptom medication score. Reductions in skin and nasal sensitivity were observed for some subjects with a trend for the Bet v 1 trimer to be more effective than the fragments. Treatment induced strong IgG1 and IgG4 allergen-specific antibody responses. Local injection-site reactions were most frequent in the trimer group affecting 59.5% of patients as opposed to 37.8% and 30.6% in the fragment and placebo groups, respectively. Systemic reactions were elicited more frequently by fragments. A large proportion of adverse side-effects appeared hours following injections, and might be attributable to concurrent exposure to related pollens. Conclusion Single courses of injection immunotherapy with Bet v 1 allergen derivatives showed trends towards improved well-being and reduced reactivity to specific allergen provocation, but did not yield significant improvement in the combined symptom medication score in this study.	41	83	2008	12	10.1111/j.1365-2222.2008.03042.x	Allergy; Immunology
House dust mite control measures for asthma: systematic review. The major allergen in house dust comes from mites. We performed a systematic review of the randomized trials that had assessed the effects of reducing exposure to house dust mite antigens in the homes of people with mite-sensitive asthma, and had compared active interventions with placebo or no treatment. Fifty-four trials (3002 patients) were included. Thirty-six trials assessed physical methods (26 mattress covers), 10 chemical methods and eight a combination of chemical and physical methods. Despite the fact that many trials were of poor quality and would be expected to exaggerate the reported effect, we did not find an effect of the interventions. For the most frequently reported outcome, peak flow in the morning (1565 patients), the standardized mean difference was 0.00 (95% confidence interval (CI) -0.10 to 0.10). There were no statistically significant differences in number of patients improved (relative risk 1.01, 95% CI 0.80-1.27), asthma symptom scores (standardized mean difference -0.04, 95% CI -0.15 to 0.07) or in medication usage (standardized mean difference -0.06, 95% CI -0.18 to 0.07). Chemical and physical methods aimed at reducing exposure to house dust mite allergens cannot be recommended.. asthma| house dust mites| systematic review|randomized controlled-trial| impermeable bed covers| sensitive adult asthma| double-blind trial| allergen-avoidance| benzyl-benzoate| high-efficiency| mattress encasings| childhood asthma| bronchial hyperreactivity.	JUN-2008	asthma| house dust mites| systematic review|randomized controlled-trial| impermeable bed covers| sensitive adult asthma| double-blind trial| allergen-avoidance| benzyl-benzoate| high-efficiency| mattress encasings| childhood asthma| bronchial hyperreactivity	Gotzsche, PC; Johansen, HK	House dust mite control measures for asthma: systematic review		ALLERGY	asthma; house dust mites; systematic review	RANDOMIZED CONTROLLED-TRIAL; IMPERMEABLE BED COVERS; SENSITIVE ADULT ASTHMA; DOUBLE-BLIND TRIAL; ALLERGEN-AVOIDANCE; BENZYL-BENZOATE; HIGH-EFFICIENCY; MATTRESS ENCASINGS; CHILDHOOD ASTHMA; BRONCHIAL HYPERREACTIVITY	The major allergen in house dust comes from mites. We performed a systematic review of the randomized trials that had assessed the effects of reducing exposure to house dust mite antigens in the homes of people with mite-sensitive asthma, and had compared active interventions with placebo or no treatment. Fifty-four trials (3002 patients) were included. Thirty-six trials assessed physical methods (26 mattress covers), 10 chemical methods and eight a combination of chemical and physical methods. Despite the fact that many trials were of poor quality and would be expected to exaggerate the reported effect, we did not find an effect of the interventions. For the most frequently reported outcome, peak flow in the morning (1565 patients), the standardized mean difference was 0.00 (95% confidence interval (CI) -0.10 to 0.10). There were no statistically significant differences in number of patients improved (relative risk 1.01, 95% CI 0.80-1.27), asthma symptom scores (standardized mean difference -0.04, 95% CI -0.15 to 0.07) or in medication usage (standardized mean difference -0.06, 95% CI -0.18 to 0.07). Chemical and physical methods aimed at reducing exposure to house dust mite allergens cannot be recommended.	94	83	2008	14	10.1111/j.1398-9995.2008.01690.x	Allergy; Immunology
Function and regulation of SPLUNC1 protein in mycoplasma infection and allergic inflammation. Respiratory infections, including Mycoplasma pneumoniae (Mp), contribute to asthma pathobiology. To date, the mechanisms underlying the increased susceptibility of asthmatics to airway Mp infection remain unclear. Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is a recently described large airway epithelial cell-derived molecule that was predicted to exert host defense activities. However, SPLUNC1 function and regulation in an infectious or allergic milieu are still unknown. We determined host defense and anti-inflammatory functions of SPLUNC1 protein in Mp infection and the regulation of SPLUNC1 by Mp and allergic inflammation (e.g., IL-13). SPLUNC1 function was examined in Mp or human airway epithelial cell cultures by using SPLUNC1 recombinant protein, overexpression and RNA interference. Human and mouse bronchial epithelial SPLUNC1 was examined using immunostaining, Western blotting, ELISA, laser capture microdissection, and real-time PCR. Mouse models of Mp infection and allergic inflammation and air-liquid interface cultures of normal human primary bronchial epithelial cells were used to study SPLUNC1 regulation by Mp and IL-13. We found that: 1) SPLUNC1 protein decreased Mp levels and inhibited epithelial IL-8 production induced by Mp-derived lipoproteins; 2) normal human and mouse large airway epithelial cells expressed high levels of SPLUNC1; and 3) although Mp infection increased SPLUNC1, IL-13 significantly decreased SPLUNC1 expression and Mp clearance. Our results suggest that SPLUNC1 serves as a novel host defense protein against Mp and that an allergic setting markedly reduces SPLUNC1 expression, which may in part contribute to the persistent nature of bacterial infections in allergic airways.. nasal lavage fluid| chlamydia-pneumoniae| bronchial hyperresponsiveness| collagen deposition| airway inflammation| mucin expression| murine model| lung| asthma| plunc.	SEP 15-2007	nasal lavage fluid| chlamydia-pneumoniae| bronchial hyperresponsiveness| collagen deposition| airway inflammation| mucin expression| murine model| lung| asthma| plunc	Chu, HW; Thaikoottathil, J; Rino, JG; Zhang, G; Wu, Q; Moss, T; Refaeli, Y; Bowler, R; Wenzel, SE; Chen, Z; Zdunek, J; Breed, R; Young, R; Allaire, E; Martin, RJ	Function and regulation of SPLUNC1 protein in mycoplasma infection and allergic inflammation		JOURNAL OF IMMUNOLOGY		NASAL LAVAGE FLUID; CHLAMYDIA-PNEUMONIAE; BRONCHIAL HYPERRESPONSIVENESS; COLLAGEN DEPOSITION; AIRWAY INFLAMMATION; MUCIN EXPRESSION; MURINE MODEL; LUNG; ASTHMA; PLUNC	Respiratory infections, including Mycoplasma pneumoniae (Mp), contribute to asthma pathobiology. To date, the mechanisms underlying the increased susceptibility of asthmatics to airway Mp infection remain unclear. Short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein is a recently described large airway epithelial cell-derived molecule that was predicted to exert host defense activities. However, SPLUNC1 function and regulation in an infectious or allergic milieu are still unknown. We determined host defense and anti-inflammatory functions of SPLUNC1 protein in Mp infection and the regulation of SPLUNC1 by Mp and allergic inflammation (e.g., IL-13). SPLUNC1 function was examined in Mp or human airway epithelial cell cultures by using SPLUNC1 recombinant protein, overexpression and RNA interference. Human and mouse bronchial epithelial SPLUNC1 was examined using immunostaining, Western blotting, ELISA, laser capture microdissection, and real-time PCR. Mouse models of Mp infection and allergic inflammation and air-liquid interface cultures of normal human primary bronchial epithelial cells were used to study SPLUNC1 regulation by Mp and IL-13. We found that: 1) SPLUNC1 protein decreased Mp levels and inhibited epithelial IL-8 production induced by Mp-derived lipoproteins; 2) normal human and mouse large airway epithelial cells expressed high levels of SPLUNC1; and 3) although Mp infection increased SPLUNC1, IL-13 significantly decreased SPLUNC1 expression and Mp clearance. Our results suggest that SPLUNC1 serves as a novel host defense protein against Mp and that an allergic setting markedly reduces SPLUNC1 expression, which may in part contribute to the persistent nature of bacterial infections in allergic airways.	38	83	2007	8		Immunology
Contact allergy epidemics and their controls. Contact dermatitis can be severe and lead to sick leave as well as significant healthcare expenses. The aim of this review is to present the published knowledge on 6 historical epidemics of contact allergy to apply this knowledge on the prevention and control of future contact allergy epidemics. A historical review is performed on nickel, chromium, methylchloroisothiazolinone/methylisothiazolinone, methyldibromo glutaronitrile, formaldehyde, and para-phenylenediamine. The first cases of contact dermatitis are mostly occupational, whereas consumer cases appear later. There is often a latency period from the first cases are observed until an epidemic occurs, and the problem is recognized. Finally, no one seems to take responsibility of dealing with the situation, and there are no attempts of regulation until an epidemic is consolidated among consumers for many years. Steps should be taken to prevent contact allergy epidemics. It is essential that dermatologist, scientists, administrators, and consumers organize and structure known methods to accelerate the control of emerging contact allergens.. chromium| contact allergy| contact dermatitis| epidemic| formaldehyde| isothiazolinone| methyldibromo glutaronitrile| nickel| para-phenylenediamine| risk assessment|rinse-off products| patch test| kathon-cg| nickel-exposure| risk-assessment| methyldibromo glutaronitrile| ferrous sulfate| guinea-pig| hair-dyes| dermatitis.	2007	chromium| contact allergy| contact dermatitis| epidemic| formaldehyde| isothiazolinone| methyldibromo glutaronitrile| nickel| para-phenylenediamine| risk assessment|rinse-off products| patch test| kathon-cg| nickel-exposure| risk-assessment| methyldibromo glutaronitrile| ferrous sulfate| guinea-pig| hair-dyes| dermatitis	Thyssen, JP; Johansen, JD; Menne, T	Contact allergy epidemics and their controls		CONTACT DERMATITIS	chromium; contact allergy; contact dermatitis; epidemic; formaldehyde; isothiazolinone; methyldibromo glutaronitrile; nickel; para-phenylenediamine; risk assessment	RINSE-OFF PRODUCTS; PATCH TEST; KATHON-CG; NICKEL-EXPOSURE; RISK-ASSESSMENT; METHYLDIBROMO GLUTARONITRILE; FERROUS SULFATE; GUINEA-PIG; HAIR-DYES; DERMATITIS	Contact dermatitis can be severe and lead to sick leave as well as significant healthcare expenses. The aim of this review is to present the published knowledge on 6 historical epidemics of contact allergy to apply this knowledge on the prevention and control of future contact allergy epidemics. A historical review is performed on nickel, chromium, methylchloroisothiazolinone/methylisothiazolinone, methyldibromo glutaronitrile, formaldehyde, and para-phenylenediamine. The first cases of contact dermatitis are mostly occupational, whereas consumer cases appear later. There is often a latency period from the first cases are observed until an epidemic occurs, and the problem is recognized. Finally, no one seems to take responsibility of dealing with the situation, and there are no attempts of regulation until an epidemic is consolidated among consumers for many years. Steps should be taken to prevent contact allergy epidemics. It is essential that dermatologist, scientists, administrators, and consumers organize and structure known methods to accelerate the control of emerging contact allergens.	109	83	2007	11	10.1111/j.1600-0536.2006.01058.x	Allergy; Dermatology
Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation. Allergic asthma is one of the most prevalent and continuously increasing diseases in developed countries. Its clinical features include airway hyperresponsiveness and inflammation upon allergen contact. Furthermore, an emerging area of research subsumed as fetal programming evaluates the impact of environmental insults in utero on the incidence of diseases in later life. The aim of this study was to identify whether prenatal exposure to stress, which constitutes a severe environmental insult, perpetuates airway inflammation in later life. Our experiments were performed in mice and revealed that prenatally stressed adult offspring indeed show an increased vulnerability toward airway hyperresponsiveness and inflammation. Furthermore, we provide persuasive insights on dysregulated pathways of the cellular and humoral immune response upon Ag challenge in prenatally stressed adult offspring, reflected by a Th2 greater Th1 adaptive immune response and increased CCR3 and IgE levels in vivo. Additionally, APCs derived from prenatally stressed offspring trigger clonal expansion of Th2 cells in vitro. We also deliver experimental evidence for a reduced corticotrophin-releasing hormone expression in the paraventricular nucleus of adult offspring in response to prenatal stress. Furthermore, behavioral analyses indicate an increase in anxiety in these mice. In conclusion, our data will facilitate future research aiming to identify the individual impact, hierarchy, and redundancy of multiple key protagonists in airway inflammation in an interdisciplinary context. This will foster the substantiation of disease-prevention strategies, such as asthma, during the prenatal period.. pulmonary eosinophilia| asthma| cells| rat| hyperresponsiveness| pregnancy| cytokines| endotoxin| exposure| cortisol.	DEC 15-2006	pulmonary eosinophilia| asthma| cells| rat| hyperresponsiveness| pregnancy| cytokines| endotoxin| exposure| cortisol	Pincus-Knackstedt, MK; Joachim, RA; Blois, SM; Douglas, AJ; Orsal, AS; Klapp, BF; Wahn, U; Hamelmann, E; Arck, PC	Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation		JOURNAL OF IMMUNOLOGY		PULMONARY EOSINOPHILIA; ASTHMA; CELLS; RAT; HYPERRESPONSIVENESS; PREGNANCY; CYTOKINES; ENDOTOXIN; EXPOSURE; CORTISOL	Allergic asthma is one of the most prevalent and continuously increasing diseases in developed countries. Its clinical features include airway hyperresponsiveness and inflammation upon allergen contact. Furthermore, an emerging area of research subsumed as fetal programming evaluates the impact of environmental insults in utero on the incidence of diseases in later life. The aim of this study was to identify whether prenatal exposure to stress, which constitutes a severe environmental insult, perpetuates airway inflammation in later life. Our experiments were performed in mice and revealed that prenatally stressed adult offspring indeed show an increased vulnerability toward airway hyperresponsiveness and inflammation. Furthermore, we provide persuasive insights on dysregulated pathways of the cellular and humoral immune response upon Ag challenge in prenatally stressed adult offspring, reflected by a Th2 greater Th1 adaptive immune response and increased CCR3 and IgE levels in vivo. Additionally, APCs derived from prenatally stressed offspring trigger clonal expansion of Th2 cells in vitro. We also deliver experimental evidence for a reduced corticotrophin-releasing hormone expression in the paraventricular nucleus of adult offspring in response to prenatal stress. Furthermore, behavioral analyses indicate an increase in anxiety in these mice. In conclusion, our data will facilitate future research aiming to identify the individual impact, hierarchy, and redundancy of multiple key protagonists in airway inflammation in an interdisciplinary context. This will foster the substantiation of disease-prevention strategies, such as asthma, during the prenatal period.	39	83	2006	9		Immunology
Current asthma and respiratory symptoms among pupils in Shanghai, China: influence of building ventilation, nitrogen dioxide, ozone, and formaldehyde in classrooms. We investigated 10 naturally ventilated schools in Shanghai, in winter. Pupils (13-14 years) in 30 classes received a questionnaire, 1414 participated (99%). Classroom temperatures were 13-21 degrees C (mean 17 degrees C), relative air humidity was 36-82% (mean 56%). The air exchange rate was 2.9-29.4 ac/h (mean 9.1), because of window opening. Mean CO(2) exceeded 1000 ppm in 45% of the classrooms. NO(2) levels were 33-85 mu g/m(3) indoors, and 45-80 mu g/m(3) outdoors. Ozone were 1-9 mu g/m(3) indoors and 17-28 mu g/m(3) outdoors. In total, 8.9% had doctors' diagnosed asthma, 3.1% wheeze, 23.0% daytime breathlessness, 2.4% current asthma, and 2.3% asthma medication. Multiple logistic regression was applied. Observed indoor molds was associated with asthma attacks [odds ratio (OR) = 2.40: P < 0.05]. Indoor temperature was associated with daytime breathlessness (OR = 1.26 for 1 C; P < 0.001), and indoor CO(2) with current asthma (OR = 1.18 for 100 ppm; P < 0.01) and asthma medication (OR = 1.15 for 100 ppm; P < 0.05). Indoor NO(2) was associated with current asthma (OR = 1.51 for 10 mu g/m(3); P < 0.01) and asthma medication (OR = 1.45 for 10 mu g/m(3); P < 0.01). Outdoor NO(2) was associated with current asthma (OR = 1.44 for 10 mu g/m(3); P < 0.05). Indoor and outdoor ozone was negatively associated with daytime breathlessness. In conclusion, asthma symptoms among pupils in Shanghai can be influenced by lack of ventilation and outdoor air pollution from traffic.. indoor air-quality| school environment| diffusion tubes| health-survey| hong-kong| exposure| pollution| schoolchildren| prevalence| children.	DEC-2006	indoor air-quality| school environment| diffusion tubes| health-survey| hong-kong| exposure| pollution| schoolchildren| prevalence| children	Mi, YH; Norback, D; Tao, J; Mi, YL; Ferm, M	Current asthma and respiratory symptoms among pupils in Shanghai, China: influence of building ventilation, nitrogen dioxide, ozone, and formaldehyde in classrooms		INDOOR AIR		INDOOR AIR-QUALITY; SCHOOL ENVIRONMENT; DIFFUSION TUBES; HEALTH-SURVEY; HONG-KONG; EXPOSURE; POLLUTION; SCHOOLCHILDREN; PREVALENCE; CHILDREN	We investigated 10 naturally ventilated schools in Shanghai, in winter. Pupils (13-14 years) in 30 classes received a questionnaire, 1414 participated (99%). Classroom temperatures were 13-21 degrees C (mean 17 degrees C), relative air humidity was 36-82% (mean 56%). The air exchange rate was 2.9-29.4 ac/h (mean 9.1), because of window opening. Mean CO(2) exceeded 1000 ppm in 45% of the classrooms. NO(2) levels were 33-85 mu g/m(3) indoors, and 45-80 mu g/m(3) outdoors. Ozone were 1-9 mu g/m(3) indoors and 17-28 mu g/m(3) outdoors. In total, 8.9% had doctors' diagnosed asthma, 3.1% wheeze, 23.0% daytime breathlessness, 2.4% current asthma, and 2.3% asthma medication. Multiple logistic regression was applied. Observed indoor molds was associated with asthma attacks [odds ratio (OR) = 2.40: P < 0.05]. Indoor temperature was associated with daytime breathlessness (OR = 1.26 for 1 C; P < 0.001), and indoor CO(2) with current asthma (OR = 1.18 for 100 ppm; P < 0.01) and asthma medication (OR = 1.15 for 100 ppm; P < 0.05). Indoor NO(2) was associated with current asthma (OR = 1.51 for 10 mu g/m(3); P < 0.01) and asthma medication (OR = 1.45 for 10 mu g/m(3); P < 0.01). Outdoor NO(2) was associated with current asthma (OR = 1.44 for 10 mu g/m(3); P < 0.05). Indoor and outdoor ozone was negatively associated with daytime breathlessness. In conclusion, asthma symptoms among pupils in Shanghai can be influenced by lack of ventilation and outdoor air pollution from traffic.	57	83	2006	11	10.1111/j.1600-0668.2006.00439.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Natural rubber latex allergy among health care workers: A systematic review of the evidence. Background: Natural rubber latex is a recognized allergen, but a recent meta-analysis failed to find any association between latex exposure and allergy in health care workers (HCWs). Objectives: A meta-analysis was carried out under the auspices of the French National Regulatory Authority to assess the allergic risk induced by latex gloves in HCWs. Methods: The risk of work-related exposure to latex for the development of latex allergy was assessed. Prevalence and incidence rates of latex sensitization or allergy were compared in HCWs and in the general population. Exposure-response relationships were assessed in HCWs. Results: Latex allergy was found in 4.32% (range, 4.01% to 4.63%) of HCWs and in 1.37% (range, 0.43% to 2.31%) of the general population. Latex-positive skin prick test responses ranged from 2.1% to 3.7% in the general population and from 6.9% to 7.8% for the HCWs. HCWs exposed to latex showed an increased risk of hand dermatitis (odds ratio [OR], 2.46; 95% CI, 2.11-2.86), asthma or wheezing (OR, 1.55; 95% CI, 1.15-2.08), rhinoconjunctivitis (OR, 2.73; 95% CI, 1.97-3.81), and at least one generic symptom (OR, 1.27; 95% CI, 1.09-1.47). Sensitization to latex was significantly associated with asthma and rhinoconjunctivitis. By contrast, exposure to latex was not associated with a significantly increased risk of positive skin prick test responses to latex (OR, 1.47; 95% CI, 0.94-2.30). Conclusion: HCWs have an increased risk of sensitization and allergic symptoms to latex. Clinical implications: Prevention of latex allergy in HCWs is needed.. latex allergy| health care workers| ige| skin test| exposure-response relationship| meta-analysis|apprentices starting exposure| operating-room nurses| in-hospital personnel| powder-free gloves| ige antibodies| dental students| blood-donors| occupational epidemiology| respiratory symptoms| nursing staff.	AUG-2006	latex allergy| health care workers| ige| skin test| exposure-response relationship| meta-analysis|apprentices starting exposure| operating-room nurses| in-hospital personnel| powder-free gloves| ige antibodies| dental students| blood-donors| occupational epidemiology| respiratory symptoms| nursing staff	Bousquet, J; Flahault, A; Vandenplas, O; Ameille, J; Duron, JJ; Pecquet, C; Chevrie, K; Annesi-Maesano, I	Natural rubber latex allergy among health care workers: A systematic review of the evidence		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	latex allergy; health care workers; IgE; skin test; exposure-response relationship; meta-analysis	APPRENTICES STARTING EXPOSURE; OPERATING-ROOM NURSES; IN-HOSPITAL PERSONNEL; POWDER-FREE GLOVES; IGE ANTIBODIES; DENTAL STUDENTS; BLOOD-DONORS; OCCUPATIONAL EPIDEMIOLOGY; RESPIRATORY SYMPTOMS; NURSING STAFF	Background: Natural rubber latex is a recognized allergen, but a recent meta-analysis failed to find any association between latex exposure and allergy in health care workers (HCWs). Objectives: A meta-analysis was carried out under the auspices of the French National Regulatory Authority to assess the allergic risk induced by latex gloves in HCWs. Methods: The risk of work-related exposure to latex for the development of latex allergy was assessed. Prevalence and incidence rates of latex sensitization or allergy were compared in HCWs and in the general population. Exposure-response relationships were assessed in HCWs. Results: Latex allergy was found in 4.32% (range, 4.01% to 4.63%) of HCWs and in 1.37% (range, 0.43% to 2.31%) of the general population. Latex-positive skin prick test responses ranged from 2.1% to 3.7% in the general population and from 6.9% to 7.8% for the HCWs. HCWs exposed to latex showed an increased risk of hand dermatitis (odds ratio [OR], 2.46; 95% CI, 2.11-2.86), asthma or wheezing (OR, 1.55; 95% CI, 1.15-2.08), rhinoconjunctivitis (OR, 2.73; 95% CI, 1.97-3.81), and at least one generic symptom (OR, 1.27; 95% CI, 1.09-1.47). Sensitization to latex was significantly associated with asthma and rhinoconjunctivitis. By contrast, exposure to latex was not associated with a significantly increased risk of positive skin prick test responses to latex (OR, 1.47; 95% CI, 0.94-2.30). Conclusion: HCWs have an increased risk of sensitization and allergic symptoms to latex. Clinical implications: Prevention of latex allergy in HCWs is needed.	89	83	2006	8	10.1016/j.jaci.2006.03.048	Allergy; Immunology
Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Background In acute asthma inhaled beta 2-agonists are often administered to relieve bronchospasm by wet nebulisation, but some have argued that metered-dose inhalers with a holding chamber (spacer) can be equally effective. Nebulisers require a power source and need regular maintenance, and are more expensive in the community setting. Objectives To assess the effects of holding chambers (spacers) compared to nebulisers for the delivery of beta 2-agonists for acute asthma. Search strategy We last searched the Cochrane Airways Group trials register in January 2006 and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2005). Selection criteria Randomised trials in adults and children (from two years of age) with asthma, where spacer beta 2-agonist delivery was compared with wet nebulisation. Data collection and analysis Two reviewers independently applied study inclusion criteria (one reviewer for the first version of the review), extracted the data and assessed trial quality. Missing data were obtained from the authors or estimated. Results are reported with 95% confidence intervals (CI). Main results This review has been updated in January 2006 and four new trials have been added. 2066 children and 614 adults are now included in 25 trials from emergency room and community settings. In addition, six trials on in-patients with acute asthma (213 children and 28 adults) have been reviewed. Method of delivery of beta 2-agonist did not appear to affect hospital admission rates. In adults, the relative risk of admission for spacer versus nebuliser was 0.97 (95% CI 0.63 to 1.49). The relative risk for children was 0.65 (95% CI: 0.4 to 1.06). In children, length of stay in the emergency department was significantly shorter when the spacer was used, with a mean difference of -0.47 hours (95% CI: -0.58 to -0.37). Length of stay in the emergency department for adults was similar for the two delivery methods. Peak flow and forced expiratory volume were also similar for the two delivery methods. Pulse rate was lower for spacer in children, mean difference -7.6% baseline (95% CI: -9.9 to -5.3% baseline). Authors' conclusions Metered-dose inhalers with spacer produced outcomes that were at least equivalent to nebuliser delivery. Spacers may have some advantages compared to nebulisers for children with acute asthma.. metered-dose inhaler| randomized controlled-trial| air-flow obstruction| bronchodilator delivery methods| hand-held nebulizer| pear-shaped spacer| young-children| jet nebulizer| wet nebulizer| hospitalized-patients.	2006	metered-dose inhaler| randomized controlled-trial| air-flow obstruction| bronchodilator delivery methods| hand-held nebulizer| pear-shaped spacer| young-children| jet nebulizer| wet nebulizer| hospitalized-patients	Cates, CJ; Crilly, JA; Rowe, BH	Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma		COCHRANE DATABASE OF SYSTEMATIC REVIEWS		METERED-DOSE INHALER; RANDOMIZED CONTROLLED-TRIAL; AIR-FLOW OBSTRUCTION; BRONCHODILATOR DELIVERY METHODS; HAND-HELD NEBULIZER; PEAR-SHAPED SPACER; YOUNG-CHILDREN; JET NEBULIZER; WET NEBULIZER; HOSPITALIZED-PATIENTS	Background In acute asthma inhaled beta 2-agonists are often administered to relieve bronchospasm by wet nebulisation, but some have argued that metered-dose inhalers with a holding chamber (spacer) can be equally effective. Nebulisers require a power source and need regular maintenance, and are more expensive in the community setting. Objectives To assess the effects of holding chambers (spacers) compared to nebulisers for the delivery of beta 2-agonists for acute asthma. Search strategy We last searched the Cochrane Airways Group trials register in January 2006 and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2005). Selection criteria Randomised trials in adults and children (from two years of age) with asthma, where spacer beta 2-agonist delivery was compared with wet nebulisation. Data collection and analysis Two reviewers independently applied study inclusion criteria (one reviewer for the first version of the review), extracted the data and assessed trial quality. Missing data were obtained from the authors or estimated. Results are reported with 95% confidence intervals (CI). Main results This review has been updated in January 2006 and four new trials have been added. 2066 children and 614 adults are now included in 25 trials from emergency room and community settings. In addition, six trials on in-patients with acute asthma (213 children and 28 adults) have been reviewed. Method of delivery of beta 2-agonist did not appear to affect hospital admission rates. In adults, the relative risk of admission for spacer versus nebuliser was 0.97 (95% CI 0.63 to 1.49). The relative risk for children was 0.65 (95% CI: 0.4 to 1.06). In children, length of stay in the emergency department was significantly shorter when the spacer was used, with a mean difference of -0.47 hours (95% CI: -0.58 to -0.37). Length of stay in the emergency department for adults was similar for the two delivery methods. Peak flow and forced expiratory volume were also similar for the two delivery methods. Pulse rate was lower for spacer in children, mean difference -7.6% baseline (95% CI: -9.9 to -5.3% baseline). Authors' conclusions Metered-dose inhalers with spacer produced outcomes that were at least equivalent to nebuliser delivery. Spacers may have some advantages compared to nebulisers for children with acute asthma.	70	83	2006	70	10.1002/14651858.CD000052.pub2	General & Internal Medicine
Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants. Background Allergies and food reactions are common and may be associated with foods including adapted cow's milk formula. Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance. However, it is unclear whether hydrolysed formula can be advocated for prevention of allergy and food intolerance in infants without evidence of allergy or food intolerance. Objectives To determine the effect of feeding hydrolysed formulas on allergy and food intolerance in infants and children compared to adapted cow's milk or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas. To determine which infants benefit, including infants at low or high risk of allergy and infants receiving early, short term or prolonged formula feeding. Search strategy The standard search strategy of the Cochrane Neonatal Review Group was used. The review was updated with searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - March 2006), EMBASE (1980 - March 2006) and CINAHL (1982 - March 2006) and previous reviews including cross references. Selection criteria Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with > 80% follow up of participants were eligible for inclusion. Data collection and analysis Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model. Main results Two trials compared early, short termhydrolysed formula to human milk feeding. No significant difference in infant allergy or childhood cow's milk allergy (CMA) were reported. No eligible trial compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to cow's milk formula feeding. No significant benefits were reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00). Ten eligible studies compared prolonged feeding with hydrolysed formula versus cow's milk formula in high risk infants. Meta-analysis found a significant reduction in infant allergy (seven studies, 2514 infants; typical RR 0.79, 95% CI 0.66, 0.94), but not in the incidence of childhood allergy (two studies, 950 infants; typical RR 0.85, 95% CI 0.69, 1.05). There was no significant difference in infant eczema (eight studies, 2558 infants, typical RR 0.84, 95% CI 0.68, 1.04), childhood eczema incidence (two studies, 950 infants, typical RR 0.83, 95% CI 0.63, 1.10), childhood eczema prevalence (one study, 872 infants; RR 0.66, 95% CI 0.43, 1.02), or infant or childhood asthma, rhinitis and food allergy. One study reported a significant reduction in infants with CMA with confirmed atopy (RR 0.36, 95% CI 0.15, 0.89). Subgroup analysis of trials blinded to formula found no significant difference in infant allergy (four studies, 2156 infants; typical RR 0.87, 95% CI 0.69, 1.08) or childhood allergy incidence (one study, 872 infants; RR 0.91, 95% CI 0.73, 1.14). No eligible trial examined the effect of prolonged hydrolysed formula feeding on allergy beyond early childhood. There is evidence that preterm or low birthweight infants fed a hydrolysed preterm formula have significantly reduced weight gain, but not in other growth parameters (head circumference or length). Studies in term infants report no adverse effects on growth. Subgroup analysis of trials of partially hydrolysed versus cow's milk formula found a significant reduction in infant allergy (six studies, 1391 infants; typical RR 0.79, 95% CI 0.65, 0.97) but not childhood allergy, or infant or childhood asthma, eczema or rhinitis. Methodological concerns were the same as for the overall analysis. Analysis of trials of extensively hydrolysed formula versus cow's milk formula found no significant differences in allergy or food intolerance. Infants fed extensively hydrolysed formula compared with partially hydrolysed formula had a significant reduction in food allergy (two studies, 341 infants; typical RR 0.43, 95% CI 0.19, 0.99), but there was no significant difference in all allergy or any other specific allergy incidence. Comparing extensively hydrolysed casein containing formula with cow's milk formula, one study (431 infants) reported a significant reduction in childhood allergy incidence (RR 0.72, 95% CI 0.53, 0.97). Meta- analysis found a significant reduction in infant eczema (three studies, 1237 infants; typical RR 0.71, 95% CI 0.51, 0.97). One study reported a significant reduction in childhood eczema incidence (RR 0.66, 95% CI 0.44, 0.98) and prevalence (RR 0.50, 95% CI 0.27, 0.92). Authors' conclusions There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy compared to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is limited evidence that prolonged feeding with a hydrolysed formula compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. In view of methodological concerns and inconsistency of findings, further large, well designed trials comparing formulas containing partially hydrolysed whey, or extensively hydrolysed casein to cow's milk formulas are needed.. cows milk allergy| high-risk infants| amino-acid-concentrations| low-birth-weight| australian aboriginal children| dietary intervention program| different feeding regimens| partial whey hydrolysate| brief neonatal exposure| prospective follow-up.	2006	cows milk allergy| high-risk infants| amino-acid-concentrations| low-birth-weight| australian aboriginal children| dietary intervention program| different feeding regimens| partial whey hydrolysate| brief neonatal exposure| prospective follow-up	Osborn, DA; Sinn, J	Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants		COCHRANE DATABASE OF SYSTEMATIC REVIEWS		COWS MILK ALLERGY; HIGH-RISK INFANTS; AMINO-ACID-CONCENTRATIONS; LOW-BIRTH-WEIGHT; AUSTRALIAN ABORIGINAL CHILDREN; DIETARY INTERVENTION PROGRAM; DIFFERENT FEEDING REGIMENS; PARTIAL WHEY HYDROLYSATE; BRIEF NEONATAL EXPOSURE; PROSPECTIVE FOLLOW-UP	Background Allergies and food reactions are common and may be associated with foods including adapted cow's milk formula. Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance. However, it is unclear whether hydrolysed formula can be advocated for prevention of allergy and food intolerance in infants without evidence of allergy or food intolerance. Objectives To determine the effect of feeding hydrolysed formulas on allergy and food intolerance in infants and children compared to adapted cow's milk or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas. To determine which infants benefit, including infants at low or high risk of allergy and infants receiving early, short term or prolonged formula feeding. Search strategy The standard search strategy of the Cochrane Neonatal Review Group was used. The review was updated with searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - March 2006), EMBASE (1980 - March 2006) and CINAHL (1982 - March 2006) and previous reviews including cross references. Selection criteria Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with > 80% follow up of participants were eligible for inclusion. Data collection and analysis Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model. Main results Two trials compared early, short termhydrolysed formula to human milk feeding. No significant difference in infant allergy or childhood cow's milk allergy (CMA) were reported. No eligible trial compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to cow's milk formula feeding. No significant benefits were reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00). Ten eligible studies compared prolonged feeding with hydrolysed formula versus cow's milk formula in high risk infants. Meta-analysis found a significant reduction in infant allergy (seven studies, 2514 infants; typical RR 0.79, 95% CI 0.66, 0.94), but not in the incidence of childhood allergy (two studies, 950 infants; typical RR 0.85, 95% CI 0.69, 1.05). There was no significant difference in infant eczema (eight studies, 2558 infants, typical RR 0.84, 95% CI 0.68, 1.04), childhood eczema incidence (two studies, 950 infants, typical RR 0.83, 95% CI 0.63, 1.10), childhood eczema prevalence (one study, 872 infants; RR 0.66, 95% CI 0.43, 1.02), or infant or childhood asthma, rhinitis and food allergy. One study reported a significant reduction in infants with CMA with confirmed atopy (RR 0.36, 95% CI 0.15, 0.89). Subgroup analysis of trials blinded to formula found no significant difference in infant allergy (four studies, 2156 infants; typical RR 0.87, 95% CI 0.69, 1.08) or childhood allergy incidence (one study, 872 infants; RR 0.91, 95% CI 0.73, 1.14). No eligible trial examined the effect of prolonged hydrolysed formula feeding on allergy beyond early childhood. There is evidence that preterm or low birthweight infants fed a hydrolysed preterm formula have significantly reduced weight gain, but not in other growth parameters (head circumference or length). Studies in term infants report no adverse effects on growth. Subgroup analysis of trials of partially hydrolysed versus cow's milk formula found a significant reduction in infant allergy (six studies, 1391 infants; typical RR 0.79, 95% CI 0.65, 0.97) but not childhood allergy, or infant or childhood asthma, eczema or rhinitis. Methodological concerns were the same as for the overall analysis. Analysis of trials of extensively hydrolysed formula versus cow's milk formula found no significant differences in allergy or food intolerance. Infants fed extensively hydrolysed formula compared with partially hydrolysed formula had a significant reduction in food allergy (two studies, 341 infants; typical RR 0.43, 95% CI 0.19, 0.99), but there was no significant difference in all allergy or any other specific allergy incidence. Comparing extensively hydrolysed casein containing formula with cow's milk formula, one study (431 infants) reported a significant reduction in childhood allergy incidence (RR 0.72, 95% CI 0.53, 0.97). Meta- analysis found a significant reduction in infant eczema (three studies, 1237 infants; typical RR 0.71, 95% CI 0.51, 0.97). One study reported a significant reduction in childhood eczema incidence (RR 0.66, 95% CI 0.44, 0.98) and prevalence (RR 0.50, 95% CI 0.27, 0.92). Authors' conclusions There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy compared to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is limited evidence that prolonged feeding with a hydrolysed formula compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. In view of methodological concerns and inconsistency of findings, further large, well designed trials comparing formulas containing partially hydrolysed whey, or extensively hydrolysed casein to cow's milk formulas are needed.	197	83	2006	127	10.1002/14651858.CD003664.pub3	General & Internal Medicine
The global burden of selected occupational diseases and injury risks: Methodology and summary. Background A round the globe, work has a heavy impact on health. To better advise policy makers, we assessed the global burden of disease and injury due to selected occupational hazards. This article presents an overview, and describes the methodology employed in the companion studies. Methods Using the World Health Organization (WHO) Comparative Risk Assessment methodology, we applied relative risk measures to the proportions of the population exposed to selected occupational hazards to estimate attributable fractions, deaths, and disability-adjusted life years (DALYs). Numerous occupational risk factors had to be excluded due to inadequate global data. Results In 2000, the selected risk factors were responsible worldwide for 37% of back pain, 16% of hearing loss, 13% of chronic obstructive. pulmonary disease (COPD), 11% of asthma, 8% of injuries, 9% of lung cancer, and 2% of leukemia. These risks at work caused 850, 000 deaths worldwide and resulted in the loss of about 24 million years of healthy life. Needlesticks accounted for about 40% of Hepatitis B and Hepatitis C infections and 4.4% of HIV infections in health care workers. Conclusions Exposure to occupational hazards accounts for a significant proportion of the global burden of disease and injury, which could be substantially reduced through application of proven risk prevention strategies. Am. J. Ind. Med. 48:400-418, 2005. (c) 2005 Wiley-Liss, Inc.. burden of disease| occupational health| dalys| comparative risk assessment| health impact assessment|obstructive pulmonary-disease| dust exposure| united-states| asthma| disability| population| mortality| health| carcinogens| prevalence.	DEC-2005	burden of disease| occupational health| dalys| comparative risk assessment| health impact assessment|obstructive pulmonary-disease| dust exposure| united-states| asthma| disability| population| mortality| health| carcinogens| prevalence	Nelson, DI; Concha-Barrientos, M; Driscoll, T; Steenland, K; Fingerhut, M; Punnett, L; Pruss-Ustun, A; Leigh, J; Corvalan, C	The global burden of selected occupational diseases and injury risks: Methodology and summary		AMERICAN JOURNAL OF INDUSTRIAL MEDICINE	burden of disease; occupational health; DALYs; comparative risk assessment; health impact assessment	OBSTRUCTIVE PULMONARY-DISEASE; DUST EXPOSURE; UNITED-STATES; ASTHMA; DISABILITY; POPULATION; MORTALITY; HEALTH; CARCINOGENS; PREVALENCE	Background A round the globe, work has a heavy impact on health. To better advise policy makers, we assessed the global burden of disease and injury due to selected occupational hazards. This article presents an overview, and describes the methodology employed in the companion studies. Methods Using the World Health Organization (WHO) Comparative Risk Assessment methodology, we applied relative risk measures to the proportions of the population exposed to selected occupational hazards to estimate attributable fractions, deaths, and disability-adjusted life years (DALYs). Numerous occupational risk factors had to be excluded due to inadequate global data. Results In 2000, the selected risk factors were responsible worldwide for 37% of back pain, 16% of hearing loss, 13% of chronic obstructive. pulmonary disease (COPD), 11% of asthma, 8% of injuries, 9% of lung cancer, and 2% of leukemia. These risks at work caused 850, 000 deaths worldwide and resulted in the loss of about 24 million years of healthy life. Needlesticks accounted for about 40% of Hepatitis B and Hepatitis C infections and 4.4% of HIV infections in health care workers. Conclusions Exposure to occupational hazards accounts for a significant proportion of the global burden of disease and injury, which could be substantially reduced through application of proven risk prevention strategies. Am. J. Ind. Med. 48:400-418, 2005. (c) 2005 Wiley-Liss, Inc.	80	83	2005	19	10.1002/ajim.20211	Public, Environmental & Occupational Health
The development of the mucosal immune system pre- and post-weaning: balancing regulatory and effector function. The mucosal immune system fulfils the primary function of defence against potential pathogens that may enter across vulnerable surface epithelia. However, a secondary function of the intestinal immune system is to discriminate between pathogen-associated and 'harmless' antigens, expressing active responses against the former and tolerance to the latter. Control of immune responses appears to be an active process, involving local generation of IgA and of regulatory and/or regulated T lymphocytes. Two important periods of maximum exposure to novel antigens occur in the young animal, immediately after birth and at weaning. In both cases the antigenic composition of the intestinal contents can shift suddenly, as a result of a novel diet and of colonisation by novel strains and species of bacteria. Changes in lifestyles of man, and husbandry of animals, have resulted in weaning becoming much more abrupt than previously in evolution, increasing the number of antigens that must be simultaneously evaluated by neonates. Thus, birth and weaning are likely to represent hazard and critical control points in the development of appropriate responses to pathogens and harmless dietary and commensal antigens. Neonates are born with relatively undeveloped mucosal immune systems. At birth this factor may prevent both expression of active immune responses and development of tolerance. However, colonisation by intestinal flora expands the mucosal immune system in antigen-specific and non-specific ways. At weaning antibody to fed proteins can be detected, indicating active immune responses to fed proteins. It is proposed that under normal conditions the ability of the mucosal immune system to mount active responses to foreign antigens develops simultaneously with the ability to control and regulate such responses. Problems arise when one or other arm of the immune system develops inappropriately, resulting in inappropriate effector responses to harmless food proteins (allergy) or inadequate responses to pathogens (disease susceptibility).. oral tolerance| immune development| weaning| pig| allergy|growth-factor-beta| inflammatory-bowel-disease| resident intestinal flora| oral tolerance| t-cell| lamina propria| peyers-patches| spleen-cells| breast-milk| b-cell.	NOV-2005	oral tolerance| immune development| weaning| pig| allergy|growth-factor-beta| inflammatory-bowel-disease| resident intestinal flora| oral tolerance| t-cell| lamina propria| peyers-patches| spleen-cells| breast-milk| b-cell	Bailey, M; Haverson, K; Inman, C; Harris, C; Jones, P; Corfield, G; Miller, B; Stokes, C	The development of the mucosal immune system pre- and post-weaning: balancing regulatory and effector function		PROCEEDINGS OF THE NUTRITION SOCIETY	oral tolerance; immune development; weaning; pig; allergy	GROWTH-FACTOR-BETA; INFLAMMATORY-BOWEL-DISEASE; RESIDENT INTESTINAL FLORA; ORAL TOLERANCE; T-CELL; LAMINA PROPRIA; PEYERS-PATCHES; SPLEEN-CELLS; BREAST-MILK; B-CELL	The mucosal immune system fulfils the primary function of defence against potential pathogens that may enter across vulnerable surface epithelia. However, a secondary function of the intestinal immune system is to discriminate between pathogen-associated and 'harmless' antigens, expressing active responses against the former and tolerance to the latter. Control of immune responses appears to be an active process, involving local generation of IgA and of regulatory and/or regulated T lymphocytes. Two important periods of maximum exposure to novel antigens occur in the young animal, immediately after birth and at weaning. In both cases the antigenic composition of the intestinal contents can shift suddenly, as a result of a novel diet and of colonisation by novel strains and species of bacteria. Changes in lifestyles of man, and husbandry of animals, have resulted in weaning becoming much more abrupt than previously in evolution, increasing the number of antigens that must be simultaneously evaluated by neonates. Thus, birth and weaning are likely to represent hazard and critical control points in the development of appropriate responses to pathogens and harmless dietary and commensal antigens. Neonates are born with relatively undeveloped mucosal immune systems. At birth this factor may prevent both expression of active immune responses and development of tolerance. However, colonisation by intestinal flora expands the mucosal immune system in antigen-specific and non-specific ways. At weaning antibody to fed proteins can be detected, indicating active immune responses to fed proteins. It is proposed that under normal conditions the ability of the mucosal immune system to mount active responses to foreign antigens develops simultaneously with the ability to control and regulate such responses. Problems arise when one or other arm of the immune system develops inappropriately, resulting in inappropriate effector responses to harmless food proteins (allergy) or inadequate responses to pathogens (disease susceptibility).	55	83	2005	7	10.1079/PNS2005452	Nutrition & Dietetics
Cortical substrates for the perception of dyspnea. Dyspnea is a common, unpleasant, and impairing symptom in various respiratory diseases and other diseases. Despite growing understanding of the multiple peripheral mechanisms giving rise to dyspnea, little is known about the cortical mechanisms underlying its perception. The results of neuroiniaging studies have shown that distinct brain areas process the dyspneic sensation, among which the anterior insular seems to be the most important. Based on the findings of the first relevant neuroimaging studies, this review describes the cortical structures associated with the perception of dyspnea. Moreover, similarities to the perception of pain are discussed, and implications for future research are provided.. asthma| brain| breathlessness| copd| dyspnea| emission-ct| mri| pain| perception|positron-emission-tomography| cerebral blood-flow| insular cortex| air hunger| respiratory sensations| lung-volume| chemoreceptor afferents| volitional inspiration| somatosensory cortex| symptom perception.	JUL-2005	asthma| brain| breathlessness| copd| dyspnea| emission-ct| mri| pain| perception|positron-emission-tomography| cerebral blood-flow| insular cortex| air hunger| respiratory sensations| lung-volume| chemoreceptor afferents| volitional inspiration| somatosensory cortex| symptom perception	von Leupoldt, A; Dahme, B	Cortical substrates for the perception of dyspnea		CHEST	asthma; brain; breathlessness; COPD; dyspnea; emission-CT; MRI; pain; perception	POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; INSULAR CORTEX; AIR HUNGER; RESPIRATORY SENSATIONS; LUNG-VOLUME; CHEMORECEPTOR AFFERENTS; VOLITIONAL INSPIRATION; SOMATOSENSORY CORTEX; SYMPTOM PERCEPTION	Dyspnea is a common, unpleasant, and impairing symptom in various respiratory diseases and other diseases. Despite growing understanding of the multiple peripheral mechanisms giving rise to dyspnea, little is known about the cortical mechanisms underlying its perception. The results of neuroiniaging studies have shown that distinct brain areas process the dyspneic sensation, among which the anterior insular seems to be the most important. Based on the findings of the first relevant neuroimaging studies, this review describes the cortical structures associated with the perception of dyspnea. Moreover, similarities to the perception of pain are discussed, and implications for future research are provided.	108	83	2005	10	10.1378/chest.128.1.345	General & Internal Medicine; Respiratory System
Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis. Background Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms. Objective We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 mug given once daily, administered in mono-therapy or combined therapy with a H-1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season. Methods One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 mug once daily (n=20) or with FPANS 200 mug once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 mug once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage. Results All treatments showed significant differences (P<0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P<0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on daily (P<0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P<0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P<0.001) compared with PLA. Besides, there were significant differences (P<0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK. Conclusion The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.. cetirizine| eosinophil cationic protein| eosinophils| fluticasone propionate| montelukast| nasal lavage| parietaria| pollen season|leukotriene receptor antagonists| pollen season| grass-pollen| double-blind| propionate| corticosteroids| asthma| antileukotriene| levocabastine| eosinophils.	FEB-2004	cetirizine| eosinophil cationic protein| eosinophils| fluticasone propionate| montelukast| nasal lavage| parietaria| pollen season|leukotriene receptor antagonists| pollen season| grass-pollen| double-blind| propionate| corticosteroids| asthma| antileukotriene| levocabastine| eosinophils	Di Lorenzo, G; Pacor, ML; Pellitteri, ME; Morici, G; Di Gregoli, A; Lo Bianco, C; Ditta, V; Martinelli, N; Candore, G; Mansueto, P; Rini, GB; Corrocher, R; Caruso, C	Randomized placebo-controlled trial comparing fluticasone aqueous nasal spray in mono-therapy, fluticasone plus cetirizine, fluticasone plus montelukast and cetirizine plus montelukast for seasonal allergic rhinitis		CLINICAL AND EXPERIMENTAL ALLERGY	cetirizine; eosinophil cationic protein; eosinophils; fluticasone propionate; montelukast; nasal lavage; Parietaria; pollen season	LEUKOTRIENE RECEPTOR ANTAGONISTS; POLLEN SEASON; GRASS-POLLEN; DOUBLE-BLIND; PROPIONATE; CORTICOSTEROIDS; ASTHMA; ANTILEUKOTRIENE; LEVOCABASTINE; EOSINOPHILS	Background Corticosteroids are considered to be particularly effective in reducing nasal congestion and are therefore recommended as first-line treatment in allergic rhinitis patients with moderate to severe and/or persistent symptoms. Objective We compared the clinical efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 mug given once daily, administered in mono-therapy or combined therapy with a H-1 receptor antagonist (cetirizine, CTZ) or with a leukotriene antagonist (montelukast, MSK), and the combined therapy of CTZ plus MSK in the treatment of patients affected by allergic rhinitis to Parietaria during natural pollen exposure. In addition, we examined the effect of the treatment on eosinophil counts and eosinophil cationic protein (ECP) in nasal lavage performed at beginning of season, during season and at the end of the season. Methods One hundred patients aged 12-50 years (mean+/-SD 31.8+/-9.6) with a history of moderate to severe Parietaria pollen-induced seasonal allergic rhinitis were selected. A randomized, double-blind, double dummy, placebo (PLA)-controlled, parallel-group study design was used. Patients were treated FPANS 200 mug once daily (n=20) or with FPANS 200 mug once daily, plus CTZ (10 mg) in the morning (n=20), or with FPANS 200 mug once daily, plus MSK (10 mg) in the evening (n=20) or with CTZ (10 mg) in the morning plus MSK in the evening (n=20) or matched PLA (n=20). Assessment of efficacy was based on scores of daily nasal symptoms and on eosinophil counts and ECP in nasal lavage. Results All treatments showed significant differences (P<0.001) compared with PLA in terms of total symptom, rhinorrhea, sneezing and nasal itching scores. Concerning nasal congestion on waking and daily only the groups treated with FPANS in mono-therapy or in combined therapy showed significant differences compared with PLA. Comparing the group treated with FPANS alone and the groups treated with FPANS plus CTZ, we found significant differences for total symptom score (P=0.04) and for nasal itching (P=0.003). The comparison between FPANS plus CTZ and FPANS plus MSK showed significant difference for nasal itching (P=0.003). Finally, there were significant differences between the group treated with FPANS and the group treated with CTZ plus MSK for total symptom score (P=0.009), for nasal congestion on waking (P<0.001) and nasal congestion daily (P<0.001). Also the comparisons between the group treated with FPANS plus CTZ and the group treated with CTZ plus MSK demonstrated significant differences (P<0.001) for total symptom, for nasal congestion on waking and for nasal congestion on daily, for rhinorrhea (P=0.04) and for nasal itching (P=0.003) scores. Concerning the comparison between the group treated with FPANS plus MSK and the group treated with CTZ plus MSK we found significant differences for total symptom score (P=0.005), for nasal congestion on waking (P<0.001) and for nasal congestion on daily (P<0.001). No other differences were observed between the groups. Concerning blood eosinophil counts, significant differences were found between the treatments with FPANS in mono-therapy or in combined therapy with PLA group during and at the end of the season (P=0.0003 and P<0.0001, respectively). Concerning eosinophils and ECP in nasal lavage, all treatments showed significant differences (P<0.001) compared with PLA. Besides, there were significant differences (P<0.001) between the groups treated with FPANS alone or in combined therapy and the group treated with CTZ plus MSK. Conclusion The results of this comparative study demonstrate that FPANS is highly effective for treating patients affected by allergic rhinitis, with efficacy exceeding that of CTZ plus MSK in combined therapy. In addition, the regular combined therapy of FPANS plus CTZ or plus MSK would not seem to offer substantial advantage with respect to FPANS in mono-therapy in patients affected by seasonal allergic rhinitis.	35	83	2004	9	10.1111/j.1365-2222.2004.01877.x	Allergy; Immunology
Insights into the pathogenesis of asthma utilizing murine models. Asthma is a common syndrome in children and adults. Despite the increasing prevalence and socioeconomic burden, the underlying pathophysiology remains poorly defined in a large percentage of asthmatics. Animal models and, in particular, murine models of allergic airway disease have helped to reveal some of the potential underlying mechanisms and have played an important role in identifying the importance of T cells and T(H)2 cytokines in development of allergen-induced inflammation and airway hyperresponsiveness. In addition, other cell types including mast cells and eosinophils have been implicated in the development of some aspects of the disease. To further understand this complex syndrome, the development of animal models which mimic elements of this chronic airway disease is essential. Copyright (C) 2004 S. Karger AG, Basel.. asthma| mouse model| airway hyperresponsiveness|delta-t-cells| allergic airway disease| respiratory syncytial virus| activated mast-cells| nf-kappa-b| mouse model| pulmonary eosinophilia| mucus production| bronchial hyperreactivity| antigen exposure.	2004	asthma| mouse model| airway hyperresponsiveness|delta-t-cells| allergic airway disease| respiratory syncytial virus| activated mast-cells| nf-kappa-b| mouse model| pulmonary eosinophilia| mucus production| bronchial hyperreactivity| antigen exposure	Taube, C; Dakhama, A; Gelfand, EW	Insights into the pathogenesis of asthma utilizing murine models		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	asthma; mouse model; airway hyperresponsiveness	DELTA-T-CELLS; ALLERGIC AIRWAY DISEASE; RESPIRATORY SYNCYTIAL VIRUS; ACTIVATED MAST-CELLS; NF-KAPPA-B; MOUSE MODEL; PULMONARY EOSINOPHILIA; MUCUS PRODUCTION; BRONCHIAL HYPERREACTIVITY; ANTIGEN EXPOSURE	Asthma is a common syndrome in children and adults. Despite the increasing prevalence and socioeconomic burden, the underlying pathophysiology remains poorly defined in a large percentage of asthmatics. Animal models and, in particular, murine models of allergic airway disease have helped to reveal some of the potential underlying mechanisms and have played an important role in identifying the importance of T cells and T(H)2 cytokines in development of allergen-induced inflammation and airway hyperresponsiveness. In addition, other cell types including mast cells and eosinophils have been implicated in the development of some aspects of the disease. To further understand this complex syndrome, the development of animal models which mimic elements of this chronic airway disease is essential. Copyright (C) 2004 S. Karger AG, Basel.	161	83	2004	14	10.1159/000080899	Allergy; Immunology
Indoor air pollution from biomass combustion and acute respiratory illness in preschool age children in Zimbabwe. Background Reliance on biomass for cooking and heating exposes many women and young children in developing countries to high levels of air pollution indoors. This study investigated the association between household use of biomass fuels for cooking and acute respiratory infections (ARI) in preschool age children (<5 years) in Zimbabwe. Methods Analysis is based on 3559 children age 0-59 months included in the 1999 Zimbabwe Demographic and Health Survey (ZDHS). Children who suffered from cough accompanied by short, rapid breathing during the 2 weeks preceding the survey were defined as having suffered from ARI. Logistic regression was used to estimate the odds of suffering from ARI among children from households using biomass fuels (wood, dung, or straw) relative to children from households using cleaner fuels (liquid petroleum gas [LPG]/natural gas, or electricity), after controlling for potentially confounding factors. Results About two-thirds (66%) of children lived in households using biomass fuels and 16% suffered from ARI during the 2 weeks preceding the survey interview. After adjusting for child's age, sex, birth order, nutritional status, mother's age at childbirth, education, religion, household living standard, and region of residence, children in households using wood, dung, or straw for cooking were more than twice as likely to have suffered from ARI as children from households using LPG/natural gas or electricity (OR = 2.20; 95% CI: 1.16, 4.19). Conclusions Household use of high pollution biomass fuels is associated with ARI in children in Zimbabwe. The relationship needs to be further investigated using more direct measures of smoke exposure and clinical measures of ARI.. indoor air pollution| biomass| smoke| respiratory tract infections| child| zimbabwe|environmental tobacco-smoke| developing-countries| chronic-bronchitis| immune-response| lung immunity| bone-marrow| exposure| disease| women| asthma.	OCT-2003	indoor air pollution| biomass| smoke| respiratory tract infections| child| zimbabwe|environmental tobacco-smoke| developing-countries| chronic-bronchitis| immune-response| lung immunity| bone-marrow| exposure| disease| women| asthma	Mishra, V	Indoor air pollution from biomass combustion and acute respiratory illness in preschool age children in Zimbabwe		INTERNATIONAL JOURNAL OF EPIDEMIOLOGY	indoor air pollution; biomass; smoke; respiratory tract infections; child; Zimbabwe	ENVIRONMENTAL TOBACCO-SMOKE; DEVELOPING-COUNTRIES; CHRONIC-BRONCHITIS; IMMUNE-RESPONSE; LUNG IMMUNITY; BONE-MARROW; EXPOSURE; DISEASE; WOMEN; ASTHMA	Background Reliance on biomass for cooking and heating exposes many women and young children in developing countries to high levels of air pollution indoors. This study investigated the association between household use of biomass fuels for cooking and acute respiratory infections (ARI) in preschool age children (<5 years) in Zimbabwe. Methods Analysis is based on 3559 children age 0-59 months included in the 1999 Zimbabwe Demographic and Health Survey (ZDHS). Children who suffered from cough accompanied by short, rapid breathing during the 2 weeks preceding the survey were defined as having suffered from ARI. Logistic regression was used to estimate the odds of suffering from ARI among children from households using biomass fuels (wood, dung, or straw) relative to children from households using cleaner fuels (liquid petroleum gas [LPG]/natural gas, or electricity), after controlling for potentially confounding factors. Results About two-thirds (66%) of children lived in households using biomass fuels and 16% suffered from ARI during the 2 weeks preceding the survey interview. After adjusting for child's age, sex, birth order, nutritional status, mother's age at childbirth, education, religion, household living standard, and region of residence, children in households using wood, dung, or straw for cooking were more than twice as likely to have suffered from ARI as children from households using LPG/natural gas or electricity (OR = 2.20; 95% CI: 1.16, 4.19). Conclusions Household use of high pollution biomass fuels is associated with ARI in children in Zimbabwe. The relationship needs to be further investigated using more direct measures of smoke exposure and clinical measures of ARI.	61	83	2003	7	10.1093/ije/dyg240	Public, Environmental & Occupational Health
Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomyosin, in unexposed Orthodox Jews. Background Assessment of allergic (IgE antibody-mediated) reactions to foods may become complicated by cross-reactivity that can occur among certain food families and between foods and seemingly unrelated allergens. Objective The allergenic properties of tropomyosin (muscle-derived protein) have been recently demonstrated in invertebrates such as cockroaches, dust mites, and shrimp. In view of a possible cross-reactivity between food allergens and related allergens from animal sources, we designed a study to assess IgE antibody reactivity to the major shrimp allergen, Pen a 1, in an unexposed population of Orthodox Jews, who observe Kosher dietary laws that prohibit eating shellfish. Methods Nine subjects, who reacted positively by skin tests to shrimp (Penaeus setiferous ), were selected for the study. Subjects (two females, seven males) ranged in age from 14 to 32 years (mean 20.4). All subjects were strictly observant of Jewish tradition and had no prior exposure to seafood (regarded as a non-Kosher food). Serum was obtained from all the subjects and tested for IgE antibody reactivity to shrimp and dust mite. Results All subjects reported symptoms of perennial allergic rhinitis, five had history of asthma, atopic dermatitis, and/or sinusitis. All had positive skin prick tests to shrimp and house dust mite (HDM) (Dermatophagoides farinae, D. pteronyssinus , or both); 2/7 subjects were positive to cockroach mix (Blattella germanica and Periplaneta americana ). Sera of 4/9 subjects demonstrated specific IgE antibodies by RAST to shrimp (7.0-20.0%), 3/9 to Pen a 1 (6.3-24.1%), and 3/9 to shrimp or Pen a 1 by immunoblot. IgE binding to Pen a 1 was inhibited with either mite or cockroach extracts as demonstrated by RAST and/or immunoblot inhibition analysis. Conclusions These studies indicate that IgE antibody reactivity to a major food allergen, shrimp, can occur in an unexposed population of individuals; some subjects allergic to HDM and/or cockroach show substantial IgE antibody reactivity to the major shrimp allergen Pen a 1 (tropomyosin). Based on inhibition with cockroach and/or dust mite extracts, this reactivity appears to be due to cross-reacting tropomyosins.. allergen cross-reactivity| cockroaches| dust mites| orthodox jews| shrimp reactivity| tropomyosin|house-dust mite| cross-reactivity| dermatophagoides-pteronyssinus| identification| nitrocellulose| hypersensitivity| proteins| binding| snails.	JUL-2003	allergen cross-reactivity| cockroaches| dust mites| orthodox jews| shrimp reactivity| tropomyosin|house-dust mite| cross-reactivity| dermatophagoides-pteronyssinus| identification| nitrocellulose| hypersensitivity| proteins| binding| snails	Fernandes, J; Reshef, A; Patton, L; Ayuso, R; Reese, G; Lehrer, SB	Immunoglobulin E antibody reactivity to the major shrimp allergen, tropomyosin, in unexposed Orthodox Jews		CLINICAL AND EXPERIMENTAL ALLERGY	allergen cross-reactivity; cockroaches; dust mites; Orthodox Jews; shrimp reactivity; tropomyosin	HOUSE-DUST MITE; CROSS-REACTIVITY; DERMATOPHAGOIDES-PTERONYSSINUS; IDENTIFICATION; NITROCELLULOSE; HYPERSENSITIVITY; PROTEINS; BINDING; SNAILS	Background Assessment of allergic (IgE antibody-mediated) reactions to foods may become complicated by cross-reactivity that can occur among certain food families and between foods and seemingly unrelated allergens. Objective The allergenic properties of tropomyosin (muscle-derived protein) have been recently demonstrated in invertebrates such as cockroaches, dust mites, and shrimp. In view of a possible cross-reactivity between food allergens and related allergens from animal sources, we designed a study to assess IgE antibody reactivity to the major shrimp allergen, Pen a 1, in an unexposed population of Orthodox Jews, who observe Kosher dietary laws that prohibit eating shellfish. Methods Nine subjects, who reacted positively by skin tests to shrimp (Penaeus setiferous ), were selected for the study. Subjects (two females, seven males) ranged in age from 14 to 32 years (mean 20.4). All subjects were strictly observant of Jewish tradition and had no prior exposure to seafood (regarded as a non-Kosher food). Serum was obtained from all the subjects and tested for IgE antibody reactivity to shrimp and dust mite. Results All subjects reported symptoms of perennial allergic rhinitis, five had history of asthma, atopic dermatitis, and/or sinusitis. All had positive skin prick tests to shrimp and house dust mite (HDM) (Dermatophagoides farinae, D. pteronyssinus , or both); 2/7 subjects were positive to cockroach mix (Blattella germanica and Periplaneta americana ). Sera of 4/9 subjects demonstrated specific IgE antibodies by RAST to shrimp (7.0-20.0%), 3/9 to Pen a 1 (6.3-24.1%), and 3/9 to shrimp or Pen a 1 by immunoblot. IgE binding to Pen a 1 was inhibited with either mite or cockroach extracts as demonstrated by RAST and/or immunoblot inhibition analysis. Conclusions These studies indicate that IgE antibody reactivity to a major food allergen, shrimp, can occur in an unexposed population of individuals; some subjects allergic to HDM and/or cockroach show substantial IgE antibody reactivity to the major shrimp allergen Pen a 1 (tropomyosin). Based on inhibition with cockroach and/or dust mite extracts, this reactivity appears to be due to cross-reacting tropomyosins.	32	83	2003	6	10.1046/j.1365-2222.2003.01722.x	Allergy; Immunology
"Atopic dermatitis and asthma: Parallels in the evolution of treatment. Objectives. To review epidemiologic correlations between asthma and atopic dermatitis (AD), identify common features in disease pathophysiology, and review steps involved in the development of asthma therapy guidelines to assess the appropriateness of a similar process and approach for AD. Methods. A 7-member panel representing specialists in dermatology, allergy, asthma, immunology, and pediatrics from around the United States convened to review the current literature and evolving data on AD. Participants presented reviews to the panel on the epidemiology of asthma and AD, the genetic predisposition to allergic disease, the current understanding of the immunopathophysiology of AD, interrelationships between the pathologic pathways of asthma and AD, evolving treatment concepts and options in AD, and the applicability of the asthma treatment model and how it may be adapted for guideline development for AD. Commentary and criticism were recorded for use in document preparation. Results. There are clear epidemiologic parallels in asthma and AD. Importantly, AD frequently is the first manifestation of an atopic diathesis, which occurs in genetically predisposed individuals and also includes asthma and allergic rhinitis. Up to 80% of children with AD will eventually develop allergic rhinitis or asthma later in childhood. This classic ""atopic triad"" has numerous pathophysiologic elements in common, including cyclic nucleotide regulatory abnormalities, immune cell alterations, and inflammatory mediators and allergic triggers. New therapeutic options that target underlying immune mechanisms are available, and their place among treatments for AD is becoming established. Guidelines of care have been developed for asthma. The panel noted that the National Institutes of Health/National Heart, Lung, and Blood Institute guidelines for diagnosis and management of asthma, first issued in 1991, had a tremendous positive impact on many aspects of asthma treatment. It not only created a heightened awareness that asthma is a disease of chronic inflammation, but it also provided unified approaches for therapy and opened new areas of basic science and clinical research. In addition, the guidelines spurred interactions among physicians of various specialties and stimulated a great quantity of research in asthma therapy. It is anticipated that AD therapy guidelines would have similar positive outcomes. Conclusions. The panel concluded that, on the basis of current information and evolving therapeutic options, a clear rationale exists to support AD guideline development. The many parallels between AD and asthma suggest that processes and approaches used for the asthma therapy guidelines would be appropriate for AD.. allergy| asthma| atopic dermatitis| treatment guidelines|dendritic cells| early-life| childhood| prevalence| allergy| epidemiology| population| exposure| linkage| intervention."	MAR-2003	allergy| asthma| atopic dermatitis| treatment guidelines|dendritic cells| early-life| childhood| prevalence| allergy| epidemiology| population| exposure| linkage| intervention	Eichenfield, LF; Hanifin, JM; Beck, LA; Lemanske, RF; Sampson, HA; Weiss, ST; Leung, DYM	Atopic dermatitis and asthma: Parallels in the evolution of treatment		PEDIATRICS	allergy; asthma; atopic dermatitis; treatment guidelines	DENDRITIC CELLS; EARLY-LIFE; CHILDHOOD; PREVALENCE; ALLERGY; EPIDEMIOLOGY; POPULATION; EXPOSURE; LINKAGE; INTERVENTION	"Objectives. To review epidemiologic correlations between asthma and atopic dermatitis (AD), identify common features in disease pathophysiology, and review steps involved in the development of asthma therapy guidelines to assess the appropriateness of a similar process and approach for AD. Methods. A 7-member panel representing specialists in dermatology, allergy, asthma, immunology, and pediatrics from around the United States convened to review the current literature and evolving data on AD. Participants presented reviews to the panel on the epidemiology of asthma and AD, the genetic predisposition to allergic disease, the current understanding of the immunopathophysiology of AD, interrelationships between the pathologic pathways of asthma and AD, evolving treatment concepts and options in AD, and the applicability of the asthma treatment model and how it may be adapted for guideline development for AD. Commentary and criticism were recorded for use in document preparation. Results. There are clear epidemiologic parallels in asthma and AD. Importantly, AD frequently is the first manifestation of an atopic diathesis, which occurs in genetically predisposed individuals and also includes asthma and allergic rhinitis. Up to 80% of children with AD will eventually develop allergic rhinitis or asthma later in childhood. This classic ""atopic triad"" has numerous pathophysiologic elements in common, including cyclic nucleotide regulatory abnormalities, immune cell alterations, and inflammatory mediators and allergic triggers. New therapeutic options that target underlying immune mechanisms are available, and their place among treatments for AD is becoming established. Guidelines of care have been developed for asthma. The panel noted that the National Institutes of Health/National Heart, Lung, and Blood Institute guidelines for diagnosis and management of asthma, first issued in 1991, had a tremendous positive impact on many aspects of asthma treatment. It not only created a heightened awareness that asthma is a disease of chronic inflammation, but it also provided unified approaches for therapy and opened new areas of basic science and clinical research. In addition, the guidelines spurred interactions among physicians of various specialties and stimulated a great quantity of research in asthma therapy. It is anticipated that AD therapy guidelines would have similar positive outcomes. Conclusions. The panel concluded that, on the basis of current information and evolving therapeutic options, a clear rationale exists to support AD guideline development. The many parallels between AD and asthma suggest that processes and approaches used for the asthma therapy guidelines would be appropriate for AD."	63	83	2003	9	10.1542/peds.111.3.608	Pediatrics
Therapeutic significance of distal airway inflammation in asthma. Inflammation In asthma is not merely confined to the large central airways but also extends to the small peripheral airways. Distal lung inflammation can be observed even In patients with asthma with mild disease and normal spirometric readings. Subjects with asymptomatic asthma can exhibit significant Increases In peripheral airway resistance, likely the result of distal lung inflammation. As determined from measurements of eosinophilic and other cellular infiltrates, the inflammatory response in the distal lung can exceed that in the large airways. Nocturnal asthma, a natural model of cyclic asthma worsening, is associated with an increase in nighttime distal lung inflammation, as evidenced by the accumulation of alveolar tissue eosinophils. Distal lung disease appears to Increase the risk of recurrent asthma exacerbation, whereas disease-related anatomic changes in the small airways of the distal lung are prominent in fatal asthma. The clinical significance of distal lung disease makes this region an important therapeutic target. Chlorofluorocarbon (CFC)-based preparations of inhaled corticosteroids used to treat airway inflammation produce aerosols of relatively large particle size (similar to4 mum); such aerosols have poor access to the distal lung. New formulations of Inhaled corticosteroids that use hydrofluoroalkane (HFA) propellants can have smaller particle sizes (similar to1 mum). Extrafine HFA aerosols have better access to the distal lung, with less oropharyngeal deposition. Imaging studies suggest that anti-inflammatory medication delivered as an extrafine aerosol produces beneficial changes in distal lung function. In one study, an HFA formulation of an inhaled corticosteroid reduced air trapping to a greater degree than a CFC formulation of the same corticosteroid. By extending the delivery of anti-inflammatory medication to the distal lung, the new HFA-based corticosteroids have the potential to treat asthma more effectively and at reduced steroid doses.. asthma| distal airway inflammation| nocturnal asthma| inhaled corticosteroids| chlorofluorocarbon-based preparations| hydrofluoroalkane propellants|inhaled beclomethasone dipropionate| obstructive pulmonary-disease| metered-dose inhaler| long-term treatment| nocturnal asthma| pseudophysiologic emphysema| eosinophilic inflammation| triamcinolone acetonide| fluticasone propionate| peripheral airways.	FEB-2002	asthma| distal airway inflammation| nocturnal asthma| inhaled corticosteroids| chlorofluorocarbon-based preparations| hydrofluoroalkane propellants|inhaled beclomethasone dipropionate| obstructive pulmonary-disease| metered-dose inhaler| long-term treatment| nocturnal asthma| pseudophysiologic emphysema| eosinophilic inflammation| triamcinolone acetonide| fluticasone propionate| peripheral airways	Martin, RJ	Therapeutic significance of distal airway inflammation in asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; distal airway inflammation; nocturnal asthma; inhaled corticosteroids; chlorofluorocarbon-based preparations; hydrofluoroalkane propellants	INHALED BECLOMETHASONE DIPROPIONATE; OBSTRUCTIVE PULMONARY-DISEASE; METERED-DOSE INHALER; LONG-TERM TREATMENT; NOCTURNAL ASTHMA; PSEUDOPHYSIOLOGIC EMPHYSEMA; EOSINOPHILIC INFLAMMATION; TRIAMCINOLONE ACETONIDE; FLUTICASONE PROPIONATE; PERIPHERAL AIRWAYS	Inflammation In asthma is not merely confined to the large central airways but also extends to the small peripheral airways. Distal lung inflammation can be observed even In patients with asthma with mild disease and normal spirometric readings. Subjects with asymptomatic asthma can exhibit significant Increases In peripheral airway resistance, likely the result of distal lung inflammation. As determined from measurements of eosinophilic and other cellular infiltrates, the inflammatory response in the distal lung can exceed that in the large airways. Nocturnal asthma, a natural model of cyclic asthma worsening, is associated with an increase in nighttime distal lung inflammation, as evidenced by the accumulation of alveolar tissue eosinophils. Distal lung disease appears to Increase the risk of recurrent asthma exacerbation, whereas disease-related anatomic changes in the small airways of the distal lung are prominent in fatal asthma. The clinical significance of distal lung disease makes this region an important therapeutic target. Chlorofluorocarbon (CFC)-based preparations of inhaled corticosteroids used to treat airway inflammation produce aerosols of relatively large particle size (similar to4 mum); such aerosols have poor access to the distal lung. New formulations of Inhaled corticosteroids that use hydrofluoroalkane (HFA) propellants can have smaller particle sizes (similar to1 mum). Extrafine HFA aerosols have better access to the distal lung, with less oropharyngeal deposition. Imaging studies suggest that anti-inflammatory medication delivered as an extrafine aerosol produces beneficial changes in distal lung function. In one study, an HFA formulation of an inhaled corticosteroid reduced air trapping to a greater degree than a CFC formulation of the same corticosteroid. By extending the delivery of anti-inflammatory medication to the distal lung, the new HFA-based corticosteroids have the potential to treat asthma more effectively and at reduced steroid doses.	71	83	2002	14	10.1067/mai.2002.121409	Allergy; Immunology
The effect of allergen-induced airway inflammation on airway remodeling in a murine model of allergic asthma. Objective and design: We examined the effect of airway inflammation on airway remodeling and bronchial responsiveness in a mouse model of allergic asthma. Materials and methods: BALB/c mice were sensitized to ovalbumin (OA), and exposed to aerosolized OA (0.01, 0.1 and 1%). Twenty-four hours after the final antigen challenge, bronchial responsiveness was measured, and bronchoalveolar lavage (BAL) and histological examinations were carried out. Results: Repeated antigen exposure induced airway inflammation, IgE/IgG1 responses, epithelial changes, collagen deposition in the lungs, subepithelial fibrosis associated with increases in the amount of transforming growth factor (TGF)-beta1 in BAL fluid (BALF), and bronchial hyperresponsiveness to acetylcholine. The number of eosinophils in BALF was significantly correlated with TGF-beta1 production in BALF and the amount of hydroxyproline. Furthermore, significant correlations were found between these fibrogenic parameters and the bronchial responsiveness. Conclusion: These findings demonstrated that in this murine model airway eosinophilic inflammation is responsible for the development of airway remodeling as well as bronchial hyperresponsiveness in allergic bronchial asthma.. airway inflammation| bronchial hyperresponsiveness| goblet cells| subepithelial fibrosis| tgf-beta 1|growth-factor-beta| bronchial hyperresponsiveness| pulmonary fibrosis| cell hyperplasia| expression| mice| collagen| exposure| responsiveness| methacholine.	DEC-2001	airway inflammation| bronchial hyperresponsiveness| goblet cells| subepithelial fibrosis| tgf-beta 1|growth-factor-beta| bronchial hyperresponsiveness| pulmonary fibrosis| cell hyperplasia| expression| mice| collagen| exposure| responsiveness| methacholine	Tanaka, H; Masuda, T; Tokuoka, S; Komai, M; Nagao, K; Takahashi, Y; Nagai, H	The effect of allergen-induced airway inflammation on airway remodeling in a murine model of allergic asthma		INFLAMMATION RESEARCH	airway inflammation; bronchial hyperresponsiveness; goblet cells; subepithelial fibrosis; TGF-beta 1	GROWTH-FACTOR-BETA; BRONCHIAL HYPERRESPONSIVENESS; PULMONARY FIBROSIS; CELL HYPERPLASIA; EXPRESSION; MICE; COLLAGEN; EXPOSURE; RESPONSIVENESS; METHACHOLINE	Objective and design: We examined the effect of airway inflammation on airway remodeling and bronchial responsiveness in a mouse model of allergic asthma. Materials and methods: BALB/c mice were sensitized to ovalbumin (OA), and exposed to aerosolized OA (0.01, 0.1 and 1%). Twenty-four hours after the final antigen challenge, bronchial responsiveness was measured, and bronchoalveolar lavage (BAL) and histological examinations were carried out. Results: Repeated antigen exposure induced airway inflammation, IgE/IgG1 responses, epithelial changes, collagen deposition in the lungs, subepithelial fibrosis associated with increases in the amount of transforming growth factor (TGF)-beta1 in BAL fluid (BALF), and bronchial hyperresponsiveness to acetylcholine. The number of eosinophils in BALF was significantly correlated with TGF-beta1 production in BALF and the amount of hydroxyproline. Furthermore, significant correlations were found between these fibrogenic parameters and the bronchial responsiveness. Conclusion: These findings demonstrated that in this murine model airway eosinophilic inflammation is responsible for the development of airway remodeling as well as bronchial hyperresponsiveness in allergic bronchial asthma.	36	83	2001	9	10.1007/PL00000243	Cell Biology; Immunology
Ambient urban Baltimore particulate-induced airway hyperresponsiveness and inflammation in mice. Airborne particulate matter (PM) is hypothesized. to play a role in increases in asthma prevalence, although a causal relationship has yet to be established. To investigate the effects of real-world PM exposure on airway reactivity (AHR) and bronchoalveolar lavage (BAL) cellularity, we exposed naive mice to a single dose (0.5 mg/ mouse) of ambient PM, coal fly ash, or diesel PM. We found that ambient PM exposure induced increases in AHR and BAL cellularity, whereas diesel PM induced significant increases in BAL cellularity, but not AHR. On the other hand, coal fly ash exposure did not elicit significant changes in either of these parameters. We further examined ambient PM-induced temporal changes in AHR, BAL cells, and lung cytakine levels over a 2-wk period. Ambient PM-induced AHR was sustained over 7 d. The increase in AHR was preceded by dramatic increases in BAL eosinophils, whereas a decline in AHR was associated with increases. in macrophages. A Th2 cytokine pattern (IL-5, IL-13, eotaxin) was observed early on with a shift toward a Th1 pattern (IFN-gamma). In additional studies, we found that the active component(s) of ambient PM are not water-soluble and that ambient PM-induced AHR and inflammation are dose-dependent. We conclude that ambient PM can induce asthmalike parameters in naive mice, suggesting that PM exposure may be an important factor in increases in asthma prevalence.. air pollution| allergy| asthma| inflammation|diesel exhaust particles| respiratory-disease| lung injury| pollution| metals| hyperreactivity| expression.	OCT 15-2001	air pollution| allergy| asthma| inflammation|diesel exhaust particles| respiratory-disease| lung injury| pollution| metals| hyperreactivity| expression	Walters, DM; Breysse, PN; Wills-Karp, M	Ambient urban Baltimore particulate-induced airway hyperresponsiveness and inflammation in mice		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	air pollution; allergy; asthma; inflammation	DIESEL EXHAUST PARTICLES; RESPIRATORY-DISEASE; LUNG INJURY; POLLUTION; METALS; HYPERREACTIVITY; EXPRESSION	Airborne particulate matter (PM) is hypothesized. to play a role in increases in asthma prevalence, although a causal relationship has yet to be established. To investigate the effects of real-world PM exposure on airway reactivity (AHR) and bronchoalveolar lavage (BAL) cellularity, we exposed naive mice to a single dose (0.5 mg/ mouse) of ambient PM, coal fly ash, or diesel PM. We found that ambient PM exposure induced increases in AHR and BAL cellularity, whereas diesel PM induced significant increases in BAL cellularity, but not AHR. On the other hand, coal fly ash exposure did not elicit significant changes in either of these parameters. We further examined ambient PM-induced temporal changes in AHR, BAL cells, and lung cytakine levels over a 2-wk period. Ambient PM-induced AHR was sustained over 7 d. The increase in AHR was preceded by dramatic increases in BAL eosinophils, whereas a decline in AHR was associated with increases. in macrophages. A Th2 cytokine pattern (IL-5, IL-13, eotaxin) was observed early on with a shift toward a Th1 pattern (IFN-gamma). In additional studies, we found that the active component(s) of ambient PM are not water-soluble and that ambient PM-induced AHR and inflammation are dose-dependent. We conclude that ambient PM can induce asthmalike parameters in naive mice, suggesting that PM exposure may be an important factor in increases in asthma prevalence.	24	83	2001	6		General & Internal Medicine; Respiratory System
Occupational asthma. The workplace can be responsible for approximately one in 10 cases of adult-onset asthma. Two types of occupational asthma (OA) are distinguished by whether they arise after a latency period that is necessary for acquiring sensitization or as a result of acute exposure to irritant materials (irritant-induced asthma). The pathophysiology of OA with a latency period is similar to that of nonoccupational asthma, whereas the mechanism of irritant-induced asthma is still uncertain. HLA haplotypes and other genetic polymorphisms have been found to be associated with OA. According to various sources of data, the overall frequency of OA has remained stable in the last 10 years, although the frequency of causal agents vary. Registers of causal occupations and agents have been issued on Web sites (eg, www.asmanet.com). Improved sampling methods have shown that the degree of exposure plays a key role in the onset of the disease, whereas prospective data collected in high-risk workplaces have also identified personal risk factors (eg, atopy, smoking, and rhinoconjunctivitis). A diagnosis of OA should no longer be based on a compatible history only but should be confirmed by means of objective testing. Once the diagnosis is confirmed, the worker should be removed from exposure, and satisfactory compensation programs should be offered, the most important being retraining programs with financial compensations because affected workers are generally young. The cost-effectiveness of prevention programs in high-risk workforces should be assessed.. asthma| occupational asthma| irritant-induced asthma| reactive airways dysfunction syndrome|western red cedar| airways dysfunction syndrome| isocyanate-induced asthma| toluene diisocyanate tdi| molecular-weight agents| exhaled nitric-oxide| hla class-ii| bronchial-mucosa| ige antibodies| adult asthma.	SEP-2001	asthma| occupational asthma| irritant-induced asthma| reactive airways dysfunction syndrome|western red cedar| airways dysfunction syndrome| isocyanate-induced asthma| toluene diisocyanate tdi| molecular-weight agents| exhaled nitric-oxide| hla class-ii| bronchial-mucosa| ige antibodies| adult asthma	Malo, JL; Chan-Yeung, M	Occupational asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; occupational asthma; irritant-induced asthma; reactive airways dysfunction syndrome	WESTERN RED CEDAR; AIRWAYS DYSFUNCTION SYNDROME; ISOCYANATE-INDUCED ASTHMA; TOLUENE DIISOCYANATE TDI; MOLECULAR-WEIGHT AGENTS; EXHALED NITRIC-OXIDE; HLA CLASS-II; BRONCHIAL-MUCOSA; IGE ANTIBODIES; ADULT ASTHMA	The workplace can be responsible for approximately one in 10 cases of adult-onset asthma. Two types of occupational asthma (OA) are distinguished by whether they arise after a latency period that is necessary for acquiring sensitization or as a result of acute exposure to irritant materials (irritant-induced asthma). The pathophysiology of OA with a latency period is similar to that of nonoccupational asthma, whereas the mechanism of irritant-induced asthma is still uncertain. HLA haplotypes and other genetic polymorphisms have been found to be associated with OA. According to various sources of data, the overall frequency of OA has remained stable in the last 10 years, although the frequency of causal agents vary. Registers of causal occupations and agents have been issued on Web sites (eg, www.asmanet.com). Improved sampling methods have shown that the degree of exposure plays a key role in the onset of the disease, whereas prospective data collected in high-risk workplaces have also identified personal risk factors (eg, atopy, smoking, and rhinoconjunctivitis). A diagnosis of OA should no longer be based on a compatible history only but should be confirmed by means of objective testing. Once the diagnosis is confirmed, the worker should be removed from exposure, and satisfactory compensation programs should be offered, the most important being retraining programs with financial compensations because affected workers are generally young. The cost-effectiveness of prevention programs in high-risk workforces should be assessed.	91	83	2001	12	10.1067/mai.2001.116432	Allergy; Immunology
Correlation of spring spore concentrations and meteorological conditions in Tulsa, Oklahoma. Different spore types are abundant in the atmosphere depending on the weather conditions. Ascospores generally follow precipitation, while spore types such as Atternaria and Cladosporium are abundant in dry conditions. This project attempted to correlate fungal spore concentrations with meteorological data from Tulsa, Oklahoma during May 1998 and May 1999, Air samples were collected and analyzed by the 12-traverse method. The spore types included were Cladosporium, Alternaria, Epicoccum, Curvularia, Pithomyces, Drechslera. smut spores, ascospores, basidiospores, and other spores. Weather variables included precipitation levels, temperature, dew point, air pressure. wind speed, wind direction and wind gusts. There were over 242.57 mm of rainfall in May 1999 and only 64.01 mm in May 1998. The most abundant spore types during May 1998 and May 1999 were Cladosporium, ascospores, and basidiospores. Results showed that there were significant differences in the dry-air spora between May 1998 and May 1999. There were twice as many Cladosporium in May 1998 as in May 1999; both ascospores and basidiospores showed little change. Multiple regression analysis was used to determine which meteorological variables influenced spore concentrations. Results showed that there was no single model for all spore types. Different combinations of factors were predictors of concentration for the various fungi examined: however. temperature and dew point seemed to be the most important meteorological factors.. aerobiology| cladosporium| basidiospores| ascospores| multiple regression|environmental-factors| airborne| populations| alternaria| release| asthma.	JUL-2001	aerobiology| cladosporium| basidiospores| ascospores| multiple regression|environmental-factors| airborne| populations| alternaria| release| asthma	Troutt, C; Levetin, E	Correlation of spring spore concentrations and meteorological conditions in Tulsa, Oklahoma		INTERNATIONAL JOURNAL OF BIOMETEOROLOGY	aerobiology; Cladosporium; basidiospores; ascospores; multiple regression	ENVIRONMENTAL-FACTORS; AIRBORNE; POPULATIONS; ALTERNARIA; RELEASE; ASTHMA	Different spore types are abundant in the atmosphere depending on the weather conditions. Ascospores generally follow precipitation, while spore types such as Atternaria and Cladosporium are abundant in dry conditions. This project attempted to correlate fungal spore concentrations with meteorological data from Tulsa, Oklahoma during May 1998 and May 1999, Air samples were collected and analyzed by the 12-traverse method. The spore types included were Cladosporium, Alternaria, Epicoccum, Curvularia, Pithomyces, Drechslera. smut spores, ascospores, basidiospores, and other spores. Weather variables included precipitation levels, temperature, dew point, air pressure. wind speed, wind direction and wind gusts. There were over 242.57 mm of rainfall in May 1999 and only 64.01 mm in May 1998. The most abundant spore types during May 1998 and May 1999 were Cladosporium, ascospores, and basidiospores. Results showed that there were significant differences in the dry-air spora between May 1998 and May 1999. There were twice as many Cladosporium in May 1998 as in May 1999; both ascospores and basidiospores showed little change. Multiple regression analysis was used to determine which meteorological variables influenced spore concentrations. Results showed that there was no single model for all spore types. Different combinations of factors were predictors of concentration for the various fungi examined: however. temperature and dew point seemed to be the most important meteorological factors.	19	83	2001	11	10.1007/s004840100087	Biophysics; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences; Physiology
Allergen and dust exposure as determinants of work-related symptoms and sensitization in a cohort of flour-exposed workers; a case-control analysis. Objectives: To estimate the incidence of specific IgE sensitization and allergic respiratory symptoms among UK bakery and flour mill workers; and to examine the roles of flour aeroallergen and total dust exposures in determining these outcomes. Methods: A cohort of 300 new employees, without previous occupational exposure to flour, were followed prospectively for a median (range) of 40 (1-91) months. Cases-defined as those developing work-related symptoms or a positive skin prick test to hour or alpha -amylase during follow up-were compared with controls, matched for duration of employment. Exposures to hour aeroallergen and total inhalable dust were estimated using a questionnaire and personal sampling techniques. Results: Incidence rates for work-related eye/nose and chest symptoms were 11.8 and 4.1 cases per 100 person years (py), respectively. Few er employees developed positive skin prick tests to hour (2.2 cases per 100 py) or alpha -amylase (2.5 cases per 100 py), Positive skin tests to occupational allergens were more common among those with new work-related symptoms. There were clear relationships between the risks of developing work-related symptoms or a positive skin prick test and three categories of estimated exposure to total dust or hour aeroallergen. Atopic employees were more likely to develop a positive skin prick test-but not work-related symptoms, These findings were unaffected by age, sex or cigarette smoking. Conclusions: In this population, many work-related symptoms which develop after first employment in modern UK bakeries or hour mills were not accompanied by evidence of IgE sensitization to flour or alpha -amylase, Although average dust exposures were within current occupational standards, the risks of development of upper and lower respiratory symptoms and of specific sensitization were clearly related to total dust and/or flour aeroallergen exposure. The incidence of work-related chest symptoms in the presence of a positive skin test to flour or alpha -amylase in this setting was approximately 1 case per 100 py, (C) 2001 British Occupational Hygiene Society. Published by Elsevier Science Ltd, All rights reserved.. sensitization| asthma| flour| alpha-amylase| bakers' asthma|bakers asthma| mills.	MAR-2001	sensitization| asthma| flour| alpha-amylase| bakers' asthma|bakers asthma| mills	Cullinan, P; Cook, A; Nieuwenhuijsen, MJ; Sandiford, C; Tee, RD; Venables, KM; McDonald, JC; Taylor, AJN	Allergen and dust exposure as determinants of work-related symptoms and sensitization in a cohort of flour-exposed workers; a case-control analysis		ANNALS OF OCCUPATIONAL HYGIENE	sensitization; asthma; flour; alpha-amylase; bakers' asthma	BAKERS ASTHMA; MILLS	Objectives: To estimate the incidence of specific IgE sensitization and allergic respiratory symptoms among UK bakery and flour mill workers; and to examine the roles of flour aeroallergen and total dust exposures in determining these outcomes. Methods: A cohort of 300 new employees, without previous occupational exposure to flour, were followed prospectively for a median (range) of 40 (1-91) months. Cases-defined as those developing work-related symptoms or a positive skin prick test to hour or alpha -amylase during follow up-were compared with controls, matched for duration of employment. Exposures to hour aeroallergen and total inhalable dust were estimated using a questionnaire and personal sampling techniques. Results: Incidence rates for work-related eye/nose and chest symptoms were 11.8 and 4.1 cases per 100 person years (py), respectively. Few er employees developed positive skin prick tests to hour (2.2 cases per 100 py) or alpha -amylase (2.5 cases per 100 py), Positive skin tests to occupational allergens were more common among those with new work-related symptoms. There were clear relationships between the risks of developing work-related symptoms or a positive skin prick test and three categories of estimated exposure to total dust or hour aeroallergen. Atopic employees were more likely to develop a positive skin prick test-but not work-related symptoms, These findings were unaffected by age, sex or cigarette smoking. Conclusions: In this population, many work-related symptoms which develop after first employment in modern UK bakeries or hour mills were not accompanied by evidence of IgE sensitization to flour or alpha -amylase, Although average dust exposures were within current occupational standards, the risks of development of upper and lower respiratory symptoms and of specific sensitization were clearly related to total dust and/or flour aeroallergen exposure. The incidence of work-related chest symptoms in the presence of a positive skin test to flour or alpha -amylase in this setting was approximately 1 case per 100 py, (C) 2001 British Occupational Hygiene Society. Published by Elsevier Science Ltd, All rights reserved.	11	83	2001	7	10.1016/S0003-4878(00)00028-4	Public, Environmental & Occupational Health; Toxicology
Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma. Th2 T cell immune-driven inflammation plays an important role in allergic asthma, We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia, OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge, Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the Lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA, Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 tells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma, Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.. brown-norway rats| induced airway hyperresponsiveness| cd4+ t-cells| interferon-gamma| ige production| atopic asthma| smooth-muscle| messenger-rna| cutting edge| murine model.	JAN 1-2001	brown-norway rats| induced airway hyperresponsiveness| cd4+ t-cells| interferon-gamma| ige production| atopic asthma| smooth-muscle| messenger-rna| cutting edge| murine model	Huang, TJ; MacAry, PA; Eynott, P; Moussavi, A; Daniel, KC; Askenase, PW; Kemeny, DM; Chung, KF	Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma		JOURNAL OF IMMUNOLOGY		BROWN-NORWAY RATS; INDUCED AIRWAY HYPERRESPONSIVENESS; CD4+ T-CELLS; INTERFERON-GAMMA; IGE PRODUCTION; ATOPIC ASTHMA; SMOOTH-MUSCLE; MESSENGER-RNA; CUTTING EDGE; MURINE MODEL	Th2 T cell immune-driven inflammation plays an important role in allergic asthma, We studied the effect of counterbalancing Th1 T cells in an asthma model in Brown Norway rats that favors Th2 responses. Rats received i.v. transfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophilia in a cell number-dependent manner. Importantly, cotransfer of OVA-specific Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia, OVA-specific Th1 cells transferred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophilia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, since cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OVA and BSA challenge, Furthermore, recipients of Th1 cells alone had increased gene expression for IFN-gamma in the Lungs, while those receiving Th2 cells alone showed increased IL-4 mRNA, Importantly, induction of these Th2 cytokines was inhibited in recipients of combined Th1 and Th2 tells. Anti-IFN-gamma treatment attenuated the down-regulatory effect of Th1 cells. Allergen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR and BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gamma, Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effective.	52	83	2001	11		Immunology
An outbreak of asthma in a modern detergent factory. The striking decrease in the occurrence of protease-induced occupational asthma in the detergent industry has been attributed to enzyme encapsulation. We report an outbreak of asthma, at least equal in sire to those reported in the 1960s, in a modern European factory which has exclusively used encapsulated enzymes. A survey revealed that enzyme sensitisation and work-related respiratory symptoms were positively correlated with airborne enzyme exposure. We suggest that encapsulation alone is insufficient to prevent enzyme-induced allergy and asthma.. enzymes.	DEC 2-2000	enzymes	Cullinan, P; Harris, JM; Taylor, AJN; Hole, AM; Jones, M; Barnes, F; Jolliffe, G	An outbreak of asthma in a modern detergent factory		LANCET		ENZYMES	The striking decrease in the occurrence of protease-induced occupational asthma in the detergent industry has been attributed to enzyme encapsulation. We report an outbreak of asthma, at least equal in sire to those reported in the 1960s, in a modern European factory which has exclusively used encapsulated enzymes. A survey revealed that enzyme sensitisation and work-related respiratory symptoms were positively correlated with airborne enzyme exposure. We suggest that encapsulation alone is insufficient to prevent enzyme-induced allergy and asthma.	5	83	2000	2	10.1016/S0140-6736(00)03264-5	General & Internal Medicine
The role of intervention in established allergy: Avoidance of indoor allergens in the treatment of chronic allergic disease. Avoidance of exposure to indoor allergens is an important element in the treatment of allergic disease. The results of several studies provide strong evidence in support of a role for allergen avoidance; however, strategies that optimize allergen reduction in houses have not been determined. Complex issues regarding the efficacy of physical and chemical measures that target house dust mite, pet, and cockroach allergens in the home are discussed. The greatest challenge is to educate allergic patients so that they can play an important role in controlling their own disease.. allergy| indoor allergens| intervention|house-dust mite| fel-d-i| particle-size distribution| placebo-controlled trial| airborne cat allergen| inner-city children| asthmatic-children| cockroach allergen| vacuum cleaners| reduce allergen.	NOV-2000	allergy| indoor allergens| intervention|house-dust mite| fel-d-i| particle-size distribution| placebo-controlled trial| airborne cat allergen| inner-city children| asthmatic-children| cockroach allergen| vacuum cleaners| reduce allergen	Platts-Mills, TAE; Vaughan, JW; Carter, MC; Woodfolk, JA	The role of intervention in established allergy: Avoidance of indoor allergens in the treatment of chronic allergic disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; indoor allergens; intervention	HOUSE-DUST MITE; FEL-D-I; PARTICLE-SIZE DISTRIBUTION; PLACEBO-CONTROLLED TRIAL; AIRBORNE CAT ALLERGEN; INNER-CITY CHILDREN; ASTHMATIC-CHILDREN; COCKROACH ALLERGEN; VACUUM CLEANERS; REDUCE ALLERGEN	Avoidance of exposure to indoor allergens is an important element in the treatment of allergic disease. The results of several studies provide strong evidence in support of a role for allergen avoidance; however, strategies that optimize allergen reduction in houses have not been determined. Complex issues regarding the efficacy of physical and chemical measures that target house dust mite, pet, and cockroach allergens in the home are discussed. The greatest challenge is to educate allergic patients so that they can play an important role in controlling their own disease.	117	83	2000	18	10.1067/mai.2000.110548	Allergy; Immunology
Airway inflammation following exposure to diesel exhaust: a study of time kinetics using induced sputum. The adverse health effects of particulate matter pollution are of increasing concern. In a recent bronchoscopic study in healthy volunteers, pronounced airway inflammation was detected following exposure to diesel exhaust (DE), The present study was conducted in order to evaluate the time kinetics of the inflammatory response following exposure to DE using induced sputum from healthy volunteers. Fifteen healthy nonsmoking volunteers were exposed to DE particles,vith a 50% cut-off aerodynamic diameter of 10 mu m 300 mu g.m(-3) and air for 1 h on two separate occasions. Sputum induction with hypertonic saline was performed 6 and 24 h after each exposure. Analyses of sputum differential cell counts and soluble protein concentrations were performed. Six hours after exposure to DE, a significant increase was found in the percentage of sputum neutrophils (37.7 versus 26.2% p=0.002) together with increases in the concentrations of interleukin-6 (12.0 versus 6.3 pg.mL(-1), p=0.006) and methylhistamine (0.11 versus 0.12 mu g.L-1, p=0.024). Irrespective of exposure, a significant increase was found in the percentage of sputum neutrophils at 24 as compared to 6 h. indicating that the procedure of sputum induction itself may change the composition of sputum. This study demonstrates that exposure to diesel exhaust induces inflammatory response in healthy human airways, represented by an early increase in interleukin-6 and methylhistamine concentration and the percentage of neutrophils. Induced sputum provides a safe tool for the investigation of the inflammatory effects of diesel exhaust, but care must be taken when interpreting results from repeated sputum inductions.. airway inflammation| diesel exhaust| induced sputum| neutrophils|epithelial-cells| healthy-subjects| daily mortality| pollution| particles| induction| counts| asthma| interleukin-6| association.	JUN-2000	airway inflammation| diesel exhaust| induced sputum| neutrophils|epithelial-cells| healthy-subjects| daily mortality| pollution| particles| induction| counts| asthma| interleukin-6| association	Nordenhall, C; Pourazar, J; Blomberg, A; Levin, JO; Sandstrom, T; Adelroth, E	Airway inflammation following exposure to diesel exhaust: a study of time kinetics using induced sputum		EUROPEAN RESPIRATORY JOURNAL	airway inflammation; diesel exhaust; induced sputum; neutrophils	EPITHELIAL-CELLS; HEALTHY-SUBJECTS; DAILY MORTALITY; POLLUTION; PARTICLES; INDUCTION; COUNTS; ASTHMA; INTERLEUKIN-6; ASSOCIATION	The adverse health effects of particulate matter pollution are of increasing concern. In a recent bronchoscopic study in healthy volunteers, pronounced airway inflammation was detected following exposure to diesel exhaust (DE), The present study was conducted in order to evaluate the time kinetics of the inflammatory response following exposure to DE using induced sputum from healthy volunteers. Fifteen healthy nonsmoking volunteers were exposed to DE particles,vith a 50% cut-off aerodynamic diameter of 10 mu m 300 mu g.m(-3) and air for 1 h on two separate occasions. Sputum induction with hypertonic saline was performed 6 and 24 h after each exposure. Analyses of sputum differential cell counts and soluble protein concentrations were performed. Six hours after exposure to DE, a significant increase was found in the percentage of sputum neutrophils (37.7 versus 26.2% p=0.002) together with increases in the concentrations of interleukin-6 (12.0 versus 6.3 pg.mL(-1), p=0.006) and methylhistamine (0.11 versus 0.12 mu g.L-1, p=0.024). Irrespective of exposure, a significant increase was found in the percentage of sputum neutrophils at 24 as compared to 6 h. indicating that the procedure of sputum induction itself may change the composition of sputum. This study demonstrates that exposure to diesel exhaust induces inflammatory response in healthy human airways, represented by an early increase in interleukin-6 and methylhistamine concentration and the percentage of neutrophils. Induced sputum provides a safe tool for the investigation of the inflammatory effects of diesel exhaust, but care must be taken when interpreting results from repeated sputum inductions.	36	83	2000	6	10.1034/j.1399-3003.2000.01512.x	Respiratory System
Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of primary school children. Non-invasive investigations of skin morphology and function are standard tools to study the pathophysiology of several cutaneous disorders, yet they have not been used in population-based epidemiological studies. Here we examined skin surface pH, stratum corneum hydration, trans-epidermal water loss (TEWL) and skin roughness by profilometry in a study population comprising 377 primary school children (8-9 years old) as part of a multicentre survey on risk factors for allergic diseases in school children. Skin surface pH showed significant higher values (p=0.029) in the group with atopic eczema (n=45) compared with the group without atopic eczema; all other parameters did not differ significantly between children,vith and without atopic eczema. With increasing skin dryness there was a significant increase in pH values (p = 0.004). Stratum corneum hydration showed a significant decrease with increasing dryness (p<0.001). Measurement of skin roughness also revealed a significant linear relationship with skin dryness (p = 0.02). It is concluded that measurement of skin surface pH, corneometry and profilometry are useful non-invasive techniques to objectively assess skin dryness in epidemiological studies regarding atopic skin disease.. skin morphology| epidemiological study| miriam (multicentre international study for risk assessment of indoor and outdoor-air pollution on allergy and eczema morbidity)| non-invasive technologies| cutaneous properties|clinically uninvolved skin| loss tewl| dry skin| dermatitis| profilometry| capacitance| parameters.	MAY-2000	skin morphology| epidemiological study| miriam (multicentre international study for risk assessment of indoor and outdoor-air pollution on allergy and eczema morbidity)| non-invasive technologies| cutaneous properties|clinically uninvolved skin| loss tewl| dry skin| dermatitis| profilometry| capacitance| parameters	Eberlein-Konig, B; Schafer, T; Huss-Marp, J; Darsow, U; Mohrenschlager, M; Herbert, O; Abeck, D; Kramer, U; Behrendt, H; Ring, J	Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of primary school children		ACTA DERMATO-VENEREOLOGICA	skin morphology; epidemiological study; MIRIAM (Multicentre International Study for Risk Assessment of Indoor and Outdoor-Air Pollution on Allergy and Eczema Morbidity); non-invasive technologies; cutaneous properties	CLINICALLY UNINVOLVED SKIN; LOSS TEWL; DRY SKIN; DERMATITIS; PROFILOMETRY; CAPACITANCE; PARAMETERS	Non-invasive investigations of skin morphology and function are standard tools to study the pathophysiology of several cutaneous disorders, yet they have not been used in population-based epidemiological studies. Here we examined skin surface pH, stratum corneum hydration, trans-epidermal water loss (TEWL) and skin roughness by profilometry in a study population comprising 377 primary school children (8-9 years old) as part of a multicentre survey on risk factors for allergic diseases in school children. Skin surface pH showed significant higher values (p=0.029) in the group with atopic eczema (n=45) compared with the group without atopic eczema; all other parameters did not differ significantly between children,vith and without atopic eczema. With increasing skin dryness there was a significant increase in pH values (p = 0.004). Stratum corneum hydration showed a significant decrease with increasing dryness (p<0.001). Measurement of skin roughness also revealed a significant linear relationship with skin dryness (p = 0.02). It is concluded that measurement of skin surface pH, corneometry and profilometry are useful non-invasive techniques to objectively assess skin dryness in epidemiological studies regarding atopic skin disease.	30	83	2000	4		Dermatology
Association of Antibiotics in Infancy With Early Childhood Obesity. IMPORTANCE Obesity in children and adults is associated with significant health burdens, making prevention a public health imperative. Infancy may be a critical period when environmental factors exert a lasting effect on the risk for obesity; identifying modifiable factors may help to reduce this risk. OBJECTIVE To assess the impact of antibiotics prescribed in infancy (ages 0-23 months) on obesity in early childhood (ages 24-59 months). DESIGN, SETTING, AND PARTICIPANTS We conducted a cohort study spanning 2001-2013 using electronic health records. Cox proportional hazard models were used to adjust for demographic, practice, and clinical covariates. The study spanned a network of primary care practices affiliated with the Children's Hospital of Philadelphia including both teaching clinics and private practices in urban Philadelphia, Pennsylvania, and the surrounding region. All children with annual visits at ages 0 to 23 months, as well 1 or more visits at ages 24 to 59 months, were enrolled. The cohort comprised 64 580 children. EXPOSURES Treatment episodes for prescribed antibiotics were ascertained up to 23 months of age. MAIN OUTCOMES AND MEASURES Obesity outcomes were determined directly from anthropometric measurements using National Health and Nutrition Examination Survey 2000 body mass index norms. RESULTS Sixty-nine percent of children were exposed to antibiotics before age 24 months, with a mean (SD) of 2.3 (1.5) episodes per child. Cumulative exposure to antibiotics was associated with later obesity (rate ratio [RR], 1.11; 95% CI, 1.02-1.21 for >= 4 episodes); this effect was stronger for broad-spectrum antibiotics (RR, 1.16; 95% CI, 1.06-1.29). Early exposure to broad-spectrum antibiotics was also associated with obesity (RR, 1.11; 95% CI, 1.03-1.19 at 0-5 months of age and RR, 1.09; 95% CI, 1.04-1.14 at 6-11 months of age) but narrow-spectrum drugs were not at any age or frequency. Steroid use, male sex, urban practice, public insurance, Hispanic ethnicity, and diagnosed asthma or wheezing were also predictors of obesity; common infectious diagnoses and antireflux medications were not. CONCLUSIONS AND RELEVANCE Repeated exposure to broad-spectrum antibiotics at ages 0 to 23 months is associated with early childhood obesity. Because common childhood infections were the most frequent diagnoses co-occurring with broad-spectrum antibiotic prescription, narrowing antibiotic selection is potentially a modifiable risk factor for childhood obesity.. infectious-diseases society| gut microbiome| otitis-media| body-mass| management| children| diagnosis| america.	NOV-2014	infectious-diseases society| gut microbiome| otitis-media| body-mass| management| children| diagnosis| america	Bailey, LC; Forrest, CB; Zhang, PX; Richards, TM; Livshits, A; DeRusso, PA	Association of Antibiotics in Infancy With Early Childhood Obesity		JAMA PEDIATRICS		INFECTIOUS-DISEASES SOCIETY; GUT MICROBIOME; OTITIS-MEDIA; BODY-MASS; MANAGEMENT; CHILDREN; DIAGNOSIS; AMERICA	IMPORTANCE Obesity in children and adults is associated with significant health burdens, making prevention a public health imperative. Infancy may be a critical period when environmental factors exert a lasting effect on the risk for obesity; identifying modifiable factors may help to reduce this risk. OBJECTIVE To assess the impact of antibiotics prescribed in infancy (ages 0-23 months) on obesity in early childhood (ages 24-59 months). DESIGN, SETTING, AND PARTICIPANTS We conducted a cohort study spanning 2001-2013 using electronic health records. Cox proportional hazard models were used to adjust for demographic, practice, and clinical covariates. The study spanned a network of primary care practices affiliated with the Children's Hospital of Philadelphia including both teaching clinics and private practices in urban Philadelphia, Pennsylvania, and the surrounding region. All children with annual visits at ages 0 to 23 months, as well 1 or more visits at ages 24 to 59 months, were enrolled. The cohort comprised 64 580 children. EXPOSURES Treatment episodes for prescribed antibiotics were ascertained up to 23 months of age. MAIN OUTCOMES AND MEASURES Obesity outcomes were determined directly from anthropometric measurements using National Health and Nutrition Examination Survey 2000 body mass index norms. RESULTS Sixty-nine percent of children were exposed to antibiotics before age 24 months, with a mean (SD) of 2.3 (1.5) episodes per child. Cumulative exposure to antibiotics was associated with later obesity (rate ratio [RR], 1.11; 95% CI, 1.02-1.21 for >= 4 episodes); this effect was stronger for broad-spectrum antibiotics (RR, 1.16; 95% CI, 1.06-1.29). Early exposure to broad-spectrum antibiotics was also associated with obesity (RR, 1.11; 95% CI, 1.03-1.19 at 0-5 months of age and RR, 1.09; 95% CI, 1.04-1.14 at 6-11 months of age) but narrow-spectrum drugs were not at any age or frequency. Steroid use, male sex, urban practice, public insurance, Hispanic ethnicity, and diagnosed asthma or wheezing were also predictors of obesity; common infectious diagnoses and antireflux medications were not. CONCLUSIONS AND RELEVANCE Repeated exposure to broad-spectrum antibiotics at ages 0 to 23 months is associated with early childhood obesity. Because common childhood infections were the most frequent diagnoses co-occurring with broad-spectrum antibiotic prescription, narrowing antibiotic selection is potentially a modifiable risk factor for childhood obesity.	20	82	2014	7	10.1001/jamapediatrics.2014.1539	Pediatrics
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P < 5 x 10(-8), including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P = 5.3 x 10(-21)); 6p21.33 near HLA-C and MICA (rs9266772, P = 3.2 x 10(-12)); 5p13.1 near PTGER4 (rs7720838, P = 8.2 x 10(-11)); 2q33.1 in PLCL1 (rs10497813, P = 6.1 x 10(-10)), 3q28 in LPP (rs9860547, P = 1.2 x 10(-9)); 20q13.2 in NFATC2 (rs6021270, P = 6.9 x 10(-9)), 4q27 in ADAD1 (rs17388568, P = 3.9 x 10(-8)); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P = 4.8 x 10(-8)). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P = 1.7 x 10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease.. disease susceptibility| atopic-dermatitis| genotype data| risk loci| t-cells| asthma| population| variants| gene| differentiation.	AUG-2013	disease susceptibility| atopic-dermatitis| genotype data| risk loci| t-cells| asthma| population| variants| gene| differentiation	Hinds, DA; McMahon, G; Kiefer, AK; Do, CB; Eriksson, N; Evans, DM; St Pourcain, B; Ring, SM; Mountain, JL; Francke, U; Davey-Smith, G; Timpson, NJ; Tung, JY	A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci		NATURE GENETICS		DISEASE SUSCEPTIBILITY; ATOPIC-DERMATITIS; GENOTYPE DATA; RISK LOCI; T-CELLS; ASTHMA; POPULATION; VARIANTS; GENE; DIFFERENTIATION	Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P < 5 x 10(-8), including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P = 5.3 x 10(-21)); 6p21.33 near HLA-C and MICA (rs9266772, P = 3.2 x 10(-12)); 5p13.1 near PTGER4 (rs7720838, P = 8.2 x 10(-11)); 2q33.1 in PLCL1 (rs10497813, P = 6.1 x 10(-10)), 3q28 in LPP (rs9860547, P = 1.2 x 10(-9)); 20q13.2 in NFATC2 (rs6021270, P = 6.9 x 10(-9)), 4q27 in ADAD1 (rs17388568, P = 3.9 x 10(-8)); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P = 4.8 x 10(-8)). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P = 1.7 x 10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease.	72	82	2013	7	10.1038/ng.2686	Genetics & Heredity
Local allergic rhinitis: Concept, pathophysiology, and management. Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a T(H)2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy. (J Allergy Clin Immunol 2012;129:1460-7.). allergic rhinitis| eosinophil cationic protein| entopy| local allergic rhinitis| local specific ige| nasal polyps| nonallergic rhinitis| nasal allergen provocation test| tryptase|persistent nonallergic rhinitis| idiopathic rhinitis| provocation test| nasal polyposis| ige antibodies| messenger-rna| mast-cells| absence| asthma| atopy.	JUN-2012	allergic rhinitis| eosinophil cationic protein| entopy| local allergic rhinitis| local specific ige| nasal polyps| nonallergic rhinitis| nasal allergen provocation test| tryptase|persistent nonallergic rhinitis| idiopathic rhinitis| provocation test| nasal polyposis| ige antibodies| messenger-rna| mast-cells| absence| asthma| atopy	Rondon, C; Campo, P; Togias, A; Fokkens, WJ; Durham, SR; Powe, DG; Mullol, J; Blanca, M	Local allergic rhinitis: Concept, pathophysiology, and management		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergic rhinitis; eosinophil cationic protein; entopy; local allergic rhinitis; local specific IgE; nasal polyps; nonallergic rhinitis; nasal allergen provocation test; tryptase	PERSISTENT NONALLERGIC RHINITIS; IDIOPATHIC RHINITIS; PROVOCATION TEST; NASAL POLYPOSIS; IGE ANTIBODIES; MESSENGER-RNA; MAST-CELLS; ABSENCE; ASTHMA; ATOPY	Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a T(H)2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy. (J Allergy Clin Immunol 2012;129:1460-7.)	27	82	2012	8	10.1016/j.jaci.2012.02.032	Allergy; Immunology
The Mannose Receptor Mediates the Uptake of Diverse Native Allergens by Dendritic Cells and Determines Allergen-Induced T Cell Polarization through Modulation of IDO Activity. The mannose receptor (MR) is a C-type lectin expressed by dendritic cells (DCs). We have investigated the ability of MR to recognize glycosylated allergens. Using a gene silencing strategy, we have specifically inhibited the expression of MR on human monocyte-derived DCs. We show that MR mediates internalization of diverse allergens from mite (Der p 1 and Der p 2), dog (Can f 1), cockroach (Bla g 2), and peanut (Ara h 1) through their carbohydrate moieties. All of these allergens bind to the C-type lectin-like carbohydrate recognition domains 4-7 of MR. We have also assessed the contribution of MR to T cell polarization after allergen exposure. We show that silencing MR expression on monocyte-derived DCs reverses the Th2 cell polarization bias, driven by Der p 1 allergen exposure, through upregulation of IDO activity. In conclusion, our work demonstrates a major role for MR in glycoallergen recognition and in the development of Th2 responses. The Journal of Immunology, 2010, 185: 1522-1531.. indoleamine 2,3-dioxygenase ido| tryptophan-metabolites| antigen presentation| experimental asthma| th2 polarization| il-4 production| responses| suppression| inhibition| maturation.	AUG 1-2010	indoleamine 2,3-dioxygenase ido| tryptophan-metabolites| antigen presentation| experimental asthma| th2 polarization| il-4 production| responses| suppression| inhibition| maturation	Royer, PJ; Emara, M; Yang, CX; Al-Ghouleh, A; Tighe, P; Jones, N; Sewell, HF; Shakib, F; Martinez-Pomares, L; Ghaemmaghami, AM	The Mannose Receptor Mediates the Uptake of Diverse Native Allergens by Dendritic Cells and Determines Allergen-Induced T Cell Polarization through Modulation of IDO Activity		JOURNAL OF IMMUNOLOGY		INDOLEAMINE 2,3-DIOXYGENASE IDO; TRYPTOPHAN-METABOLITES; ANTIGEN PRESENTATION; EXPERIMENTAL ASTHMA; TH2 POLARIZATION; IL-4 PRODUCTION; RESPONSES; SUPPRESSION; INHIBITION; MATURATION	The mannose receptor (MR) is a C-type lectin expressed by dendritic cells (DCs). We have investigated the ability of MR to recognize glycosylated allergens. Using a gene silencing strategy, we have specifically inhibited the expression of MR on human monocyte-derived DCs. We show that MR mediates internalization of diverse allergens from mite (Der p 1 and Der p 2), dog (Can f 1), cockroach (Bla g 2), and peanut (Ara h 1) through their carbohydrate moieties. All of these allergens bind to the C-type lectin-like carbohydrate recognition domains 4-7 of MR. We have also assessed the contribution of MR to T cell polarization after allergen exposure. We show that silencing MR expression on monocyte-derived DCs reverses the Th2 cell polarization bias, driven by Der p 1 allergen exposure, through upregulation of IDO activity. In conclusion, our work demonstrates a major role for MR in glycoallergen recognition and in the development of Th2 responses. The Journal of Immunology, 2010, 185: 1522-1531.	49	82	2010	10	10.4049/jimmunol.1000774	Immunology
A multicentre study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China. The prevalence of sensitization in patients with asthma and rhinitis in mainland China remains unclear. Our aim was to estimate the prevalence of allergy in patients with respiratory allergic diseases such as asthma and/or rhinitis attending respiratory clinics within mainland China. The study also investigated regional and annual differences in the prevalence and pattern of sensitization among the patients in China. A cross-sectional survey was performed in 6304 patients suffering from asthma and/or rhinitis in 17 cities from 4 regions of China. Patients completed a standardized questionnaire asking for the presence of respiratory and allergic symptoms. They also underwent skin prick tests with 13 common aeroallergens. Among the 6304 patients, 4545 (72.1%) had at least one positive skin prick reaction. The overall prevalence of positive skin prick responses was 59.0% for Dermatophagoides farinae, 57.6% for Dermatophagoides pteronyssinus, 40.7% for Blomia tropicalis, 16.1% for American cockroach, 14.0% for dog, 11.5% for Blatella germanica, 11.3% for Artemisia vulgaris, 10.3% for cat, 6.5% for Ambrosia artemisifolia, 6.3% for mixed mould I, 4.4% for mixed mould IV, 3.5% for mixed grass pollen and 2.2% for mixed tree pollen. Sensitizations to common allergens varied widely between geographical areas and demonstrated unique pattern in patients by stratification with age groups, with asthma and/or rhinitis. Severity of rhinitis and asthma was significantly correlated with skin index of reactivity to Artemisia vulgaris, Ambrosia artemisifolia and to D. pteronyssinus, D. farinae and Blomia tropicalis respectively (P < 0.001). Positive reactivity to the tested allergens and concomitant reactivity to multiple allergens including to house dust mites and Blomia tropicalis was markedly increased in patients with both asthma and rhinitis. House dust mites were the most prevalent allergens in patients with asthma and/or rhinitis in China. There were significant differences in patterns of sensitizations in patients from different geographical areas, age groups as well as asthma and/or rhinitis.. aeroallergens| asthma| epidemiology| rhinitis| sensitization| skin prick test|dermatophagoides-pteronyssinus| blomia-tropicalis| allergic rhinitis| indoor allergens| dust mites| epithelial-cells| risk-factor| children| severity| exposure.	JUL-2009	aeroallergens| asthma| epidemiology| rhinitis| sensitization| skin prick test|dermatophagoides-pteronyssinus| blomia-tropicalis| allergic rhinitis| indoor allergens| dust mites| epithelial-cells| risk-factor| children| severity| exposure	Li, J; Sun, B; Huang, Y; Lin, X; Zhao, D; Tan, G; Wu, J; Zhao, H; Cao, L; Zhong, N	A multicentre study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China		ALLERGY	aeroallergens; asthma; epidemiology; rhinitis; sensitization; skin prick test	DERMATOPHAGOIDES-PTERONYSSINUS; BLOMIA-TROPICALIS; ALLERGIC RHINITIS; INDOOR ALLERGENS; DUST MITES; EPITHELIAL-CELLS; RISK-FACTOR; CHILDREN; SEVERITY; EXPOSURE	The prevalence of sensitization in patients with asthma and rhinitis in mainland China remains unclear. Our aim was to estimate the prevalence of allergy in patients with respiratory allergic diseases such as asthma and/or rhinitis attending respiratory clinics within mainland China. The study also investigated regional and annual differences in the prevalence and pattern of sensitization among the patients in China. A cross-sectional survey was performed in 6304 patients suffering from asthma and/or rhinitis in 17 cities from 4 regions of China. Patients completed a standardized questionnaire asking for the presence of respiratory and allergic symptoms. They also underwent skin prick tests with 13 common aeroallergens. Among the 6304 patients, 4545 (72.1%) had at least one positive skin prick reaction. The overall prevalence of positive skin prick responses was 59.0% for Dermatophagoides farinae, 57.6% for Dermatophagoides pteronyssinus, 40.7% for Blomia tropicalis, 16.1% for American cockroach, 14.0% for dog, 11.5% for Blatella germanica, 11.3% for Artemisia vulgaris, 10.3% for cat, 6.5% for Ambrosia artemisifolia, 6.3% for mixed mould I, 4.4% for mixed mould IV, 3.5% for mixed grass pollen and 2.2% for mixed tree pollen. Sensitizations to common allergens varied widely between geographical areas and demonstrated unique pattern in patients by stratification with age groups, with asthma and/or rhinitis. Severity of rhinitis and asthma was significantly correlated with skin index of reactivity to Artemisia vulgaris, Ambrosia artemisifolia and to D. pteronyssinus, D. farinae and Blomia tropicalis respectively (P < 0.001). Positive reactivity to the tested allergens and concomitant reactivity to multiple allergens including to house dust mites and Blomia tropicalis was markedly increased in patients with both asthma and rhinitis. House dust mites were the most prevalent allergens in patients with asthma and/or rhinitis in China. There were significant differences in patterns of sensitizations in patients from different geographical areas, age groups as well as asthma and/or rhinitis.	49	82	2009	10	10.1111/j.1398-9995.2009.01967.x	Allergy; Immunology
Asthma disparities in urban environments. Asthma continues to disproportionately affect minority and low-income groups, with African American and Latino children who live in low-socioeconomic-status urban environments experiencing higher asthma morbidity and mortality than white children. This uneven burden in asthma morbidity has been ever increasing despite medical advancement. Many factors have contributed to these disparities in the areas of health care inequities, which result in inadequate treatment; poor housing, which leads to increased exposure to asthma allergens; and social and psychosocial stressors, which are often unappreciated. Interventions to reduce individual areas of disparities have had varying successes. Because asthma is a complex disease that affects millions of persons, multifaceted comprehensive interventions that combine all evidence-based successful strategies are essential to finally closing the gap in asthma morbidity. (J Allergy Clin Immunol 2009;123:1199-206.). asthma| disparities| children| community-based| asthma morbidity| asthma interventions|inner-city children| insurance program schip| cockroach allergen| management program| health-care| african-american| childhood asthma| controlled-trial| self-management| united-states.	JUN-2009	asthma| disparities| children| community-based| asthma morbidity| asthma interventions|inner-city children| insurance program schip| cockroach allergen| management program| health-care| african-american| childhood asthma| controlled-trial| self-management| united-states	Bryant-Stephens, T	Asthma disparities in urban environments		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Asthma; disparities; children; community-based; asthma morbidity; asthma interventions	INNER-CITY CHILDREN; INSURANCE PROGRAM SCHIP; COCKROACH ALLERGEN; MANAGEMENT PROGRAM; HEALTH-CARE; AFRICAN-AMERICAN; CHILDHOOD ASTHMA; CONTROLLED-TRIAL; SELF-MANAGEMENT; UNITED-STATES	Asthma continues to disproportionately affect minority and low-income groups, with African American and Latino children who live in low-socioeconomic-status urban environments experiencing higher asthma morbidity and mortality than white children. This uneven burden in asthma morbidity has been ever increasing despite medical advancement. Many factors have contributed to these disparities in the areas of health care inequities, which result in inadequate treatment; poor housing, which leads to increased exposure to asthma allergens; and social and psychosocial stressors, which are often unappreciated. Interventions to reduce individual areas of disparities have had varying successes. Because asthma is a complex disease that affects millions of persons, multifaceted comprehensive interventions that combine all evidence-based successful strategies are essential to finally closing the gap in asthma morbidity. (J Allergy Clin Immunol 2009;123:1199-206.)	74	82	2009	8	10.1016/j.jaci.2009.04.030	Allergy; Immunology
UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo. Background: Suppression of the adaptive immune system by UV radiation plays an important role in photocarcinogenesis. Exacerbation of skin infections has been proposed as a further consequence of UV-induced immunosuppression. Clinically bacterial infections are not a problem. For defense against bacteria, the innate immune response including the release of antimicrobial peptides is much more relevant than the adaptive immune response. Keratinocytes; have the capacity to release antimicrobial peptides. Objective: We asked whether UV radiation induces antimicrobial peptides in vitro and in vivo. Methods: Antimicrobial peptide expression by normal human keratinocytes was measured by real-time PCR and fluorescence-activated cell sorting analysis. Biopsies taken from human volunteers and skin explants were studied with immunohistochemistry. Results: Real-time PCR of normal human keratinocytes revealed a dose-dependent increase of human beta-defensin-2, -3, ribonuclease 7, and psoriasin (S100A7) after UV radiation. This was confirmed at the protein level by intracellular fluorescence-activated cell sorting and in vitro immunofluorescence analysis. Immunohistochemistry of biopsies taken from healthy volunteers exposed to different UV radiation doses revealed enhanced epidermal expression of antimicrobial peptides after UV exposure. This was also confirmed by exposing human skin explants to UV radiation. Conclusion: UV radiation exerts diverse effects on the immune system, suppressing the adaptive but inducing the innate immune response. This may explain why T-cell-mediated immune reactions are suppressed on UV exposure but not host defense reactions against bacterial attacks. (J Allergy Clin Immunol 2009;123:1117-23.). uv radiation| immunosuppression| adaptive immune response| innate immune response| antimicrobial peptides| skin| keratinocytes|normal human skin| ultraviolet-radiation| atopic-dermatitis| psoriasin s100a7| gene-expression| messenger-rna| t-cells| innate| phototherapy| infection.	MAY-2009	uv radiation| immunosuppression| adaptive immune response| innate immune response| antimicrobial peptides| skin| keratinocytes|normal human skin| ultraviolet-radiation| atopic-dermatitis| psoriasin s100a7| gene-expression| messenger-rna| t-cells| innate| phototherapy| infection	Glasser, R; Navid, F; Schuller, W; Jantschitsch, C; Harder, J; Schroder, JM; Schwarz, A; Schwarz, T	UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	UV radiation; immunosuppression; adaptive immune response; innate immune response; antimicrobial peptides; skin; keratinocytes	NORMAL HUMAN SKIN; ULTRAVIOLET-RADIATION; ATOPIC-DERMATITIS; PSORIASIN S100A7; GENE-EXPRESSION; MESSENGER-RNA; T-CELLS; INNATE; PHOTOTHERAPY; INFECTION	Background: Suppression of the adaptive immune system by UV radiation plays an important role in photocarcinogenesis. Exacerbation of skin infections has been proposed as a further consequence of UV-induced immunosuppression. Clinically bacterial infections are not a problem. For defense against bacteria, the innate immune response including the release of antimicrobial peptides is much more relevant than the adaptive immune response. Keratinocytes; have the capacity to release antimicrobial peptides. Objective: We asked whether UV radiation induces antimicrobial peptides in vitro and in vivo. Methods: Antimicrobial peptide expression by normal human keratinocytes was measured by real-time PCR and fluorescence-activated cell sorting analysis. Biopsies taken from human volunteers and skin explants were studied with immunohistochemistry. Results: Real-time PCR of normal human keratinocytes revealed a dose-dependent increase of human beta-defensin-2, -3, ribonuclease 7, and psoriasin (S100A7) after UV radiation. This was confirmed at the protein level by intracellular fluorescence-activated cell sorting and in vitro immunofluorescence analysis. Immunohistochemistry of biopsies taken from healthy volunteers exposed to different UV radiation doses revealed enhanced epidermal expression of antimicrobial peptides after UV exposure. This was also confirmed by exposing human skin explants to UV radiation. Conclusion: UV radiation exerts diverse effects on the immune system, suppressing the adaptive but inducing the innate immune response. This may explain why T-cell-mediated immune reactions are suppressed on UV exposure but not host defense reactions against bacterial attacks. (J Allergy Clin Immunol 2009;123:1117-23.)	42	82	2009	7	10.1016/j.jaci.2009.01.043	Allergy; Immunology
Mechanisms of occupational asthma. Inhalation of agents in the workplace can induce asthma in a relatively small proportion of exposed workers. Like nonoccupational asthma, occupational asthma is probably the result of multiple genetic, environmental, and behavioral influences. It is important that occupational asthma be recognized clinically because it has serious medical and socioeconomic consequences. Environmental factors that can affect the initiation of occupational asthma include the intrinsic characteristics of causative agents as well as the influence of the level and route of exposure at the workplace. The identification of host factors, polymorphisms, and candidate genes associated with occupational asthma may improve our understanding of mechanisms involved in asthma. High-molecular-weight compounds from biological sources and low-molecular-weight chemicals cause occupational asthma after a latent period of exposure. Although the clinical, functional, and pathologic features of occupational asthma caused by low-molecular-weight agents resemble those of allergic asthma, the failure to detect specific IgE antibodies against most low-molecular-weight agents has resulted in a search for alternative or complementary physiopathologic mechanisms leading to airway sensitization. Recent advances have been made in the characterization of the immune response to low-molecular-weight agents. In contrast, the mechanism of the type of occupational asthma that occurs without latency after high-level exposure to irritants remains undetermined. (J Allergy Clin Immunol 2009;123:531-42.). workplace exposure| asthma| airway hyperresponsiveness| antigen| chemical| genetics| mechanisms| inflammation|diisocyanate-induced asthma| airways dysfunction syndrome| isocyanate-induced asthma| serum-albumin conjugate| tumor-necrosis-factor| gene-environment interactions| laboratory-animal workers| western red cedar| hla class-ii| toluene diisocyanate.	MAR-2009	workplace exposure| asthma| airway hyperresponsiveness| antigen| chemical| genetics| mechanisms| inflammation|diisocyanate-induced asthma| airways dysfunction syndrome| isocyanate-induced asthma| serum-albumin conjugate| tumor-necrosis-factor| gene-environment interactions| laboratory-animal workers| western red cedar| hla class-ii| toluene diisocyanate	Maestrelli, P; Boschetto, P; Fabbri, LM; Mapp, CE	Mechanisms of occupational asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Workplace exposure; asthma; airway hyperresponsiveness; antigen; chemical; genetics; mechanisms; inflammation	DIISOCYANATE-INDUCED ASTHMA; AIRWAYS DYSFUNCTION SYNDROME; ISOCYANATE-INDUCED ASTHMA; SERUM-ALBUMIN CONJUGATE; TUMOR-NECROSIS-FACTOR; GENE-ENVIRONMENT INTERACTIONS; LABORATORY-ANIMAL WORKERS; WESTERN RED CEDAR; HLA CLASS-II; TOLUENE DIISOCYANATE	Inhalation of agents in the workplace can induce asthma in a relatively small proportion of exposed workers. Like nonoccupational asthma, occupational asthma is probably the result of multiple genetic, environmental, and behavioral influences. It is important that occupational asthma be recognized clinically because it has serious medical and socioeconomic consequences. Environmental factors that can affect the initiation of occupational asthma include the intrinsic characteristics of causative agents as well as the influence of the level and route of exposure at the workplace. The identification of host factors, polymorphisms, and candidate genes associated with occupational asthma may improve our understanding of mechanisms involved in asthma. High-molecular-weight compounds from biological sources and low-molecular-weight chemicals cause occupational asthma after a latent period of exposure. Although the clinical, functional, and pathologic features of occupational asthma caused by low-molecular-weight agents resemble those of allergic asthma, the failure to detect specific IgE antibodies against most low-molecular-weight agents has resulted in a search for alternative or complementary physiopathologic mechanisms leading to airway sensitization. Recent advances have been made in the characterization of the immune response to low-molecular-weight agents. In contrast, the mechanism of the type of occupational asthma that occurs without latency after high-level exposure to irritants remains undetermined. (J Allergy Clin Immunol 2009;123:531-42.)	144	82	2009	12	10.1016/j.jaci.2009.01.057	Allergy; Immunology
Variability of IgE reactivity profiles among European mite allergic patients. House dust mites (HDM) Dermatophagoides pteronyssinus are a frequent indoor allergen source. Our aim was to determine the frequencies of IgE reactivity to purified HDM allergen molecules in mite allergic patients from different parts of Europe in order to establish an allergen panel for diagnosis of HDM allergy. Populations of D. pteronyssinus-allergic patients from Austria (n = 56), France (n = 55), Italy (n = 67) and Sweden (n = 65) and storage mite allergic patients from Sweden (n = 31) were analysed for IgE reactivity to eight purified natural (n) and recombinant (r) D. pteronyssinus allergens (nDer p 1, rDer p 2, nDer p 4, rDer p 5, rDer p 7, rDer p 8, rDer p 10 and rDer p 14) in RAST-based dot blot assays. Using a combination of Der p 1 and Der p 2, at least 97% of the D. pteronyssinus-allergic patients could be diagnosed in each of the HDM allergic populations. However, more than 50% of the patients also reacted with other allergens and significant variabilities regarding the frequencies of IgE reactivity to individual allergen molecules were found. Patients with a predominant storage mite allergy showed none or only very weak IgE reactivity to purified D. pteronyssinus allergens. Purified Der p 1 and Der p 2 are sufficient for the diagnosis of >= 97% of D. pteronyssinus allergic patients in Europe, but other allergens may also play an important role for the diagnosis and treatment of HDM allergy. Eur J Clin Invest 2008; 38 (12): 959-965.. diagnosis| hdm allergy| ige prevalence| recombinant allergens| storage mite allergy|house-dust mite| dermatophagoides-pteronyssinus| cross-reactivity| lepidoglyphus-destructor| tyrophagus-putrescentiae| recombinant allergens| swedish farmers| storage mites| p 7| responses.	DEC-2008	diagnosis| hdm allergy| ige prevalence| recombinant allergens| storage mite allergy|house-dust mite| dermatophagoides-pteronyssinus| cross-reactivity| lepidoglyphus-destructor| tyrophagus-putrescentiae| recombinant allergens| swedish farmers| storage mites| p 7| responses	Weghofer, M; Thomas, WR; Kronqvist, M; Mari, A; Purohit, A; Pauli, G; Horak, F; Gronlund, H; Van Hage, M; Valenta, R; Vrtala, S	Variability of IgE reactivity profiles among European mite allergic patients		EUROPEAN JOURNAL OF CLINICAL INVESTIGATION	Diagnosis; HDM allergy; IgE prevalence; recombinant allergens; storage mite allergy	HOUSE-DUST MITE; DERMATOPHAGOIDES-PTERONYSSINUS; CROSS-REACTIVITY; LEPIDOGLYPHUS-DESTRUCTOR; TYROPHAGUS-PUTRESCENTIAE; RECOMBINANT ALLERGENS; SWEDISH FARMERS; STORAGE MITES; P 7; RESPONSES	House dust mites (HDM) Dermatophagoides pteronyssinus are a frequent indoor allergen source. Our aim was to determine the frequencies of IgE reactivity to purified HDM allergen molecules in mite allergic patients from different parts of Europe in order to establish an allergen panel for diagnosis of HDM allergy. Populations of D. pteronyssinus-allergic patients from Austria (n = 56), France (n = 55), Italy (n = 67) and Sweden (n = 65) and storage mite allergic patients from Sweden (n = 31) were analysed for IgE reactivity to eight purified natural (n) and recombinant (r) D. pteronyssinus allergens (nDer p 1, rDer p 2, nDer p 4, rDer p 5, rDer p 7, rDer p 8, rDer p 10 and rDer p 14) in RAST-based dot blot assays. Using a combination of Der p 1 and Der p 2, at least 97% of the D. pteronyssinus-allergic patients could be diagnosed in each of the HDM allergic populations. However, more than 50% of the patients also reacted with other allergens and significant variabilities regarding the frequencies of IgE reactivity to individual allergen molecules were found. Patients with a predominant storage mite allergy showed none or only very weak IgE reactivity to purified D. pteronyssinus allergens. Purified Der p 1 and Der p 2 are sufficient for the diagnosis of >= 97% of D. pteronyssinus allergic patients in Europe, but other allergens may also play an important role for the diagnosis and treatment of HDM allergy. Eur J Clin Invest 2008; 38 (12): 959-965.	33	82	2008	7	10.1111/j.1365-2362.2008.02048.x	General & Internal Medicine; Research & Experimental Medicine
Effects of probiotic bacteria and their genomic DNA on T(H)1/T(H)2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects. Among the factors potentially involved in the increased prevalence of allergic diseases, modification of the intestinal flora or lack of microbial exposure during childhood has been proposed. TH2-cytokines increase the production of IgE and stimulate mast cells and eosinophils, whereas T(H)1-cytokines, Such Lis IFN-gamma, may suppress IgE synthesis and Stimulate the expression of the secretory piece of IgA. Thus, a dysregulation In the expression of T(H)1- and T(H)2-cytokines may contribute to the initiation and maintenance of allergic diseases. Lactobacilli belonging to the natural intestinal rnicroflora were reported to reduce the incidence of atopic dermatitis and the severity of allergic manifestations and to modulate T(H)1/T(H)2 responses. The mechanisms still remain to be elucidated. We Sought to assess the effect of different probiotics, Lactobacillus rhamnosus GG, Lactobacillus gasseri (PA 16/8) Bifidobacterium bifidum (MP20/5), and B Bifidobacterium longum (SP07/3), on the T(H)1 I and T(H)2 responses of peripheral blood mononuclear cells (PBMCs) from healthy subjects and from patients with allergy against house dust mite to Staphylococcus enterotoxin A (SEA) and Dermatophagoides pteronyssinus (Dpt). To elucidate the Molecular basis of these effects, the effects of bacterial genomic DNA were compared with the effects of viable bacteria. PBMCs from allergic patients and from healthy donors were incubated for 24 or 48h, respectively, With Or Without SEA and Dpt allergens. The effects of preincubation with live probiotic bacteria and the effect of their genomic DNA, Lidded Simultaneously to Cultures and incubated for 24h, were assessed by measuring T(H)1/T(H)2-cytokine production. The tested live Gram-positive probiotic bacteria and their genomic DNA inhibited SEA- and Dpt-stimulated secretion of T(H)2-cytokines (IL-4 and IL-5) and enhanced the Stimulation of IFN-gamma. This effect was dose-dependent with a dosage-optimum, which was identical for all lactic acid producing bacteria (LAB) tested (10 bacteria per (PBMC) and their DNA (75 ng/rnl). Based on the maximal effects achieved with LAB and their DNA, more than 50% of the effects seem to be contributed by DNA. No significant effect was induced by the control, Gram-negative Escherichia coli TGl. Lactobacilli and bifidobacteria reduced SEA-stimulated IL-4 and IL-5 production more effectively in PBMCs from healthy subjects than from allergic patients. In contrast to this, inhibition of Dpt-stimulated IL-4- and IL-5-secretion was more pronounced in cells from allergic subjects. Compared with living LAB, bacterial DNA inhibited IL-4- and IL-5-secretion in a similar manner. SEA- and even more so Dpt-stimulated IFN-gamma stimulation by living LAB was less pronounced in allergic than in healthy Subjects, whereas IFN-gamma Stimulation by their DNA was more Pronounced in allergic subjects. The tested probiotic bacteria as well as their genomic DNA modulated the T(H)1/T(H)2 response to some allergens dose-dependently. DNA seems to contribute to 50% of the effect exerted by living bacteria in this in vitro model. The magnitude of the probiotic effects differed between healthy and allergic subjects. Whether the modulation found for the tested strains might be useful for the prevention and treatment of allergic diseases has to be assessed In clinical trials. (C) 2008 Published by Elsevier GmbH.. t(h)1/t(h)2-cytokines| immune system| allergy| probiotics| lactobacilli| bifidobacteria|lactic-acid bacteria| randomized controlled-trial| placebo-controlled trial| common cold episodes| ifn-gamma production| cpg oligodeoxynucleotides| lactobacillus-rhamnosus| atopic-dermatitis| airway inflammation| interferon-gamma.	2008	t(h)1/t(h)2-cytokines| immune system| allergy| probiotics| lactobacilli| bifidobacteria|lactic-acid bacteria| randomized controlled-trial| placebo-controlled trial| common cold episodes| ifn-gamma production| cpg oligodeoxynucleotides| lactobacillus-rhamnosus| atopic-dermatitis| airway inflammation| interferon-gamma	Ghadimi, D; Folster-Holst, R; de Vrese, M; Winkler, P; Heller, KJ; Schrezenmeir, J	Effects of probiotic bacteria and their genomic DNA on T(H)1/T(H)2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects		IMMUNOBIOLOGY	T(H)1/T(H)2-cytokines; Immune system; Allergy; Probiotics; Lactobacilli; Bifidobacteria	LACTIC-ACID BACTERIA; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; COMMON COLD EPISODES; IFN-GAMMA PRODUCTION; CPG OLIGODEOXYNUCLEOTIDES; LACTOBACILLUS-RHAMNOSUS; ATOPIC-DERMATITIS; AIRWAY INFLAMMATION; INTERFERON-GAMMA	Among the factors potentially involved in the increased prevalence of allergic diseases, modification of the intestinal flora or lack of microbial exposure during childhood has been proposed. TH2-cytokines increase the production of IgE and stimulate mast cells and eosinophils, whereas T(H)1-cytokines, Such Lis IFN-gamma, may suppress IgE synthesis and Stimulate the expression of the secretory piece of IgA. Thus, a dysregulation In the expression of T(H)1- and T(H)2-cytokines may contribute to the initiation and maintenance of allergic diseases. Lactobacilli belonging to the natural intestinal rnicroflora were reported to reduce the incidence of atopic dermatitis and the severity of allergic manifestations and to modulate T(H)1/T(H)2 responses. The mechanisms still remain to be elucidated. We Sought to assess the effect of different probiotics, Lactobacillus rhamnosus GG, Lactobacillus gasseri (PA 16/8) Bifidobacterium bifidum (MP20/5), and B Bifidobacterium longum (SP07/3), on the T(H)1 I and T(H)2 responses of peripheral blood mononuclear cells (PBMCs) from healthy subjects and from patients with allergy against house dust mite to Staphylococcus enterotoxin A (SEA) and Dermatophagoides pteronyssinus (Dpt). To elucidate the Molecular basis of these effects, the effects of bacterial genomic DNA were compared with the effects of viable bacteria. PBMCs from allergic patients and from healthy donors were incubated for 24 or 48h, respectively, With Or Without SEA and Dpt allergens. The effects of preincubation with live probiotic bacteria and the effect of their genomic DNA, Lidded Simultaneously to Cultures and incubated for 24h, were assessed by measuring T(H)1/T(H)2-cytokine production. The tested live Gram-positive probiotic bacteria and their genomic DNA inhibited SEA- and Dpt-stimulated secretion of T(H)2-cytokines (IL-4 and IL-5) and enhanced the Stimulation of IFN-gamma. This effect was dose-dependent with a dosage-optimum, which was identical for all lactic acid producing bacteria (LAB) tested (10 bacteria per (PBMC) and their DNA (75 ng/rnl). Based on the maximal effects achieved with LAB and their DNA, more than 50% of the effects seem to be contributed by DNA. No significant effect was induced by the control, Gram-negative Escherichia coli TGl. Lactobacilli and bifidobacteria reduced SEA-stimulated IL-4 and IL-5 production more effectively in PBMCs from healthy subjects than from allergic patients. In contrast to this, inhibition of Dpt-stimulated IL-4- and IL-5-secretion was more pronounced in cells from allergic subjects. Compared with living LAB, bacterial DNA inhibited IL-4- and IL-5-secretion in a similar manner. SEA- and even more so Dpt-stimulated IFN-gamma stimulation by living LAB was less pronounced in allergic than in healthy Subjects, whereas IFN-gamma Stimulation by their DNA was more Pronounced in allergic subjects. The tested probiotic bacteria as well as their genomic DNA modulated the T(H)1/T(H)2 response to some allergens dose-dependently. DNA seems to contribute to 50% of the effect exerted by living bacteria in this in vitro model. The magnitude of the probiotic effects differed between healthy and allergic subjects. Whether the modulation found for the tested strains might be useful for the prevention and treatment of allergic diseases has to be assessed In clinical trials. (C) 2008 Published by Elsevier GmbH.	50	82	2008	16	10.1016/j.imbio.2008.02.001	Immunology
Health effects of ambient air pollution in children. Children seem to be most vulnerable to the harmful effects of ambient air air pollution; pollutants because their defence mechanisms are still evolving and because they inhale a particulate matter; higher volume of air per body weight than adults. Air pollutants can also harm the foetus if nitrogen oxides; the mother is exposed to high levels of air pollution during pregnancy. An increase in oxidative stress respiratory neonatal mortality has been associated with ambient levels of air pollutants. Exposure to fine particles has been shown to increase allergen sensitisation, increase the risk of worsening asthma and decrease lung function. Lung growth, as measured by lung function, seems to be adversely affected in children exposed to various oxidant air pollutants. Oxidative stress is the main underlying mechanism responsible for the harmful effects of air pollutants and preliminary studies have indicated that antioxicant supplementation can offer some protection. (c) 2007 Elsevier Ltd. All rights reserved.. air pollution| particulate matter| nitrogen oxides| oxidative stress|diesel exhaust particles| lung-function growth| low-birth-weight| respiratory symptoms| antioxidant supplementation| allergic sensitization| asthmatic-children| particulate matter| pulmonary-function| infant-mortality.	DEC-2007	air pollution| particulate matter| nitrogen oxides| oxidative stress|diesel exhaust particles| lung-function growth| low-birth-weight| respiratory symptoms| antioxidant supplementation| allergic sensitization| asthmatic-children| particulate matter| pulmonary-function| infant-mortality	Salvi, S	Health effects of ambient air pollution in children		PAEDIATRIC RESPIRATORY REVIEWS	air pollution; particulate matter; nitrogen oxides; oxidative stress	DIESEL EXHAUST PARTICLES; LUNG-FUNCTION GROWTH; LOW-BIRTH-WEIGHT; RESPIRATORY SYMPTOMS; ANTIOXIDANT SUPPLEMENTATION; ALLERGIC SENSITIZATION; ASTHMATIC-CHILDREN; PARTICULATE MATTER; PULMONARY-FUNCTION; INFANT-MORTALITY	Children seem to be most vulnerable to the harmful effects of ambient air air pollution; pollutants because their defence mechanisms are still evolving and because they inhale a particulate matter; higher volume of air per body weight than adults. Air pollutants can also harm the foetus if nitrogen oxides; the mother is exposed to high levels of air pollution during pregnancy. An increase in oxidative stress respiratory neonatal mortality has been associated with ambient levels of air pollutants. Exposure to fine particles has been shown to increase allergen sensitisation, increase the risk of worsening asthma and decrease lung function. Lung growth, as measured by lung function, seems to be adversely affected in children exposed to various oxidant air pollutants. Oxidative stress is the main underlying mechanism responsible for the harmful effects of air pollutants and preliminary studies have indicated that antioxicant supplementation can offer some protection. (c) 2007 Elsevier Ltd. All rights reserved.	65	82	2007	6	10.1016/j.prrv.2007.08.008	Pediatrics; Respiratory System
Do indoor chemicals promote development of airway allergy?. Allergic asthma has increased worldwide in the industrialized countries. This review evaluates whether the major groups of indoor chemical exposures possess allergy-promoting (adjuvant) effects; formaldehyde was excluded, because of the size of the literature. Volatile organic compounds (VOCs) are used as an example of gases and vapors. The precipitation of asthmatic symptoms by VOC exposures is probably because of VOC levels considerably above typical indoor levels, or VOCs may be a surrogate for exposure to allergens, combustion products or dampness. Indoor particles possessed adjuvant effects in animal studies and allergy-promoting effects in humans. Quaternary ammonium compounds may possess adjuvant effects in animal studies and promoted sensitization in humans in occupational settings. The use of cleaning agents, anionic and non-ionic surfactants are not considered to possess an important adjuvant effect in the general population. Regarding phthalate exposures, results from animal and epidemiological studies were found to be discordant. There is little evidence that the indoor chemicals evaluated possess important adjuvant effects. If buildings are kept clean, dry and free of combustion products, the important question may be would it be profitable to look for lifestyle factors and non-chemical indoor exposures in order to abate airway allergy?. volatile organic compounds| quaternary ammonium compounds| cleaning agents| surfactants| phthalates| adjuvant|volatile organic-compounds| suspended particulate matter| subtilisin carlsberg alcalase| quaternary ammonium-compounds| subcutaneous injection model| ozone oxidation-products| work-related asthma| in-house dust| young-children| occupational exposures.	JUN-2007	volatile organic compounds| quaternary ammonium compounds| cleaning agents| surfactants| phthalates| adjuvant|volatile organic-compounds| suspended particulate matter| subtilisin carlsberg alcalase| quaternary ammonium-compounds| subcutaneous injection model| ozone oxidation-products| work-related asthma| in-house dust| young-children| occupational exposures	Nielsen, GD; Larsen, ST; Olsen, O; Lovik, M; Poulsen, LK; Glue, C; Wolkoff, P	Do indoor chemicals promote development of airway allergy?		INDOOR AIR	volatile organic compounds; quaternary ammonium compounds; cleaning agents; surfactants; phthalates; adjuvant	VOLATILE ORGANIC-COMPOUNDS; SUSPENDED PARTICULATE MATTER; SUBTILISIN CARLSBERG ALCALASE; QUATERNARY AMMONIUM-COMPOUNDS; SUBCUTANEOUS INJECTION MODEL; OZONE OXIDATION-PRODUCTS; WORK-RELATED ASTHMA; IN-HOUSE DUST; YOUNG-CHILDREN; OCCUPATIONAL EXPOSURES	Allergic asthma has increased worldwide in the industrialized countries. This review evaluates whether the major groups of indoor chemical exposures possess allergy-promoting (adjuvant) effects; formaldehyde was excluded, because of the size of the literature. Volatile organic compounds (VOCs) are used as an example of gases and vapors. The precipitation of asthmatic symptoms by VOC exposures is probably because of VOC levels considerably above typical indoor levels, or VOCs may be a surrogate for exposure to allergens, combustion products or dampness. Indoor particles possessed adjuvant effects in animal studies and allergy-promoting effects in humans. Quaternary ammonium compounds may possess adjuvant effects in animal studies and promoted sensitization in humans in occupational settings. The use of cleaning agents, anionic and non-ionic surfactants are not considered to possess an important adjuvant effect in the general population. Regarding phthalate exposures, results from animal and epidemiological studies were found to be discordant. There is little evidence that the indoor chemicals evaluated possess important adjuvant effects. If buildings are kept clean, dry and free of combustion products, the important question may be would it be profitable to look for lifestyle factors and non-chemical indoor exposures in order to abate airway allergy?	151	82	2007	20	10.1111/j.1600-0668.2006.00468.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Internet-based home monitoring and education of children with asthma is comparable to ideal office-based care: Results of a 1-year asthma in-home monitoring trial. OBJECTIVE. The goal was to determine whether home asthma telemonitoring with store- and- forward technology improved outcomes, compared with in- person, office- based visits. METHODS. A total of 120 patients, 6 to 17 years of age, with persistent asthma were assigned randomly to the office- based or virtual group. The 2 groups followed the same ambulatory clinical pathway for 12 months. Office- based group patients received traditional in- person education and case management. Virtual group patients received computers, Internet connections, and in- home, Internet- based case management and received education through the study Web site. Disease control outcome measures included quality of life, utilization of services, and symptom control. RESULTS. A total of 120 volunteers ( 45 female) were enrolled. The groups were clinically comparable ( office- based: 22 female/ 38 male; mean age: 9.0 +/- 3.0 years; virtual: 23 female/ 37 male; mean age: 10.2 +/- 3.1 years). Virtual patients had higher metered- dose inhaler with valved holding chamber technique scores than did the office- based group at 52 weeks ( 94% vs 89%), had greater adherence to daily asthma symptom diary submission ( 35.4% vs 20.8%), had less participant time ( 636 vs 713 patient- months), and were older. Caregivers in both groups perceived an increase in quality of life and an increase in asthma knowledge scores from baseline. There were no other differences in therapeutic or disease control outcome measures. CONCLUSIONS. Virtual group patients achieved excellent asthma therapeutic and disease control outcomes. Compared with those who received standardized officebased care, they were more adherent to diary submission and had better inhaler scores at 52 weeks. Store- and- forward telemedicine technology and case management provide additional tools to assist in the management of children with persistent asthma.. telemedicine| home| telehealth| telemonitoring| store-and-forward| clinic| case management| pediatric|metered-dose inhaler| management| telemedicine| improvement| prevention| deposition| quality| therapy| program.	MAR-2007	telemedicine| home| telehealth| telemonitoring| store-and-forward| clinic| case management| pediatric|metered-dose inhaler| management| telemedicine| improvement| prevention| deposition| quality| therapy| program	Chan, DS; Callahan, CW; Hatch-Pigott, VB; Lawless, A; Proffitt, HL; Manning, NE; Schweikert, M; Malone, FJ	Internet-based home monitoring and education of children with asthma is comparable to ideal office-based care: Results of a 1-year asthma in-home monitoring trial		PEDIATRICS	telemedicine; home; telehealth; telemonitoring; store-and-forward; clinic; case management; pediatric	METERED-DOSE INHALER; MANAGEMENT; TELEMEDICINE; IMPROVEMENT; PREVENTION; DEPOSITION; QUALITY; THERAPY; PROGRAM	OBJECTIVE. The goal was to determine whether home asthma telemonitoring with store- and- forward technology improved outcomes, compared with in- person, office- based visits. METHODS. A total of 120 patients, 6 to 17 years of age, with persistent asthma were assigned randomly to the office- based or virtual group. The 2 groups followed the same ambulatory clinical pathway for 12 months. Office- based group patients received traditional in- person education and case management. Virtual group patients received computers, Internet connections, and in- home, Internet- based case management and received education through the study Web site. Disease control outcome measures included quality of life, utilization of services, and symptom control. RESULTS. A total of 120 volunteers ( 45 female) were enrolled. The groups were clinically comparable ( office- based: 22 female/ 38 male; mean age: 9.0 +/- 3.0 years; virtual: 23 female/ 37 male; mean age: 10.2 +/- 3.1 years). Virtual patients had higher metered- dose inhaler with valved holding chamber technique scores than did the office- based group at 52 weeks ( 94% vs 89%), had greater adherence to daily asthma symptom diary submission ( 35.4% vs 20.8%), had less participant time ( 636 vs 713 patient- months), and were older. Caregivers in both groups perceived an increase in quality of life and an increase in asthma knowledge scores from baseline. There were no other differences in therapeutic or disease control outcome measures. CONCLUSIONS. Virtual group patients achieved excellent asthma therapeutic and disease control outcomes. Compared with those who received standardized officebased care, they were more adherent to diary submission and had better inhaler scores at 52 weeks. Store- and- forward telemedicine technology and case management provide additional tools to assist in the management of children with persistent asthma.	26	82	2007	10	10.1542/peds.2006-1884	Pediatrics
Investigation of the risk factors for tuberculosis: a case-control study in three countries in West Africa. Background Host-related and environment-related factors have been shown to play a role in the development of tuberculosis (TB), but few studies were carried out to identify their respective roles in resource-poor countries. Methods A multicentre case-control study was conducted in Guinee, Guinea Bissau, and The Gambia, from January 1999 to March 2001. Cases were newly detected smear positive TB patients. TWO controls were recruited for each case, one within the household of the case, and one in the community. Results Regarding host-related factors, univariate analysis by conditional logistic regression of 687 matched pairs of cases and household controls showed that TB was associated with male sex, family history of TB, absence of a BCG scar, smoking, alcohol, anaemia, HIV infection, and history and treatment of worm infection. In a multivariable model based on 601 matched pairs, male sex, family history of TB, smoking, and HIV infection were independent risk factors of TB. The investigation of environmental factors based on the comparison of 816 cases/community control pairs showed that the risk of TB was associated with single marital status, family history of TB, adult crowding, and renting the house. In a final model assessing the combined effect of host and environmental factors, TB was associated with male sex, HIV infection, smoking (with a dose-effect relationship), history of asthma, family history of TB, marital status, adult crowding, and renting the house. Conclusion TB is a multifactorial disorder, in which environment interacts with host-related factors. This study provided useful information for the assessment of host and environmental factors of TB for the improvement of TB control activities in developing countries.. tuberculosis| risk factors| epidemiology| developing countries|sub-saharan africa| pulmonary tuberculosis| socioeconomic-status| northern malawi| bcg scars| susceptibility| smoking| hiv| epidemiology| deprivation.	AUG-2005	tuberculosis| risk factors| epidemiology| developing countries|sub-saharan africa| pulmonary tuberculosis| socioeconomic-status| northern malawi| bcg scars| susceptibility| smoking| hiv| epidemiology| deprivation	Lienhardt, C; Fielding, K; Sillah, JS; Bah, B; Gustafson, P; Warndorff, D; Palayew, M; Lisse, I; Donkor, S; Diallo, S; Manneh, K; Adegbola, R; Aaby, P; Bah-Sow, O; Bennett, S; McAdam, K	Investigation of the risk factors for tuberculosis: a case-control study in three countries in West Africa		INTERNATIONAL JOURNAL OF EPIDEMIOLOGY	tuberculosis; risk factors; epidemiology; developing countries	SUB-SAHARAN AFRICA; PULMONARY TUBERCULOSIS; SOCIOECONOMIC-STATUS; NORTHERN MALAWI; BCG SCARS; SUSCEPTIBILITY; SMOKING; HIV; EPIDEMIOLOGY; DEPRIVATION	Background Host-related and environment-related factors have been shown to play a role in the development of tuberculosis (TB), but few studies were carried out to identify their respective roles in resource-poor countries. Methods A multicentre case-control study was conducted in Guinee, Guinea Bissau, and The Gambia, from January 1999 to March 2001. Cases were newly detected smear positive TB patients. TWO controls were recruited for each case, one within the household of the case, and one in the community. Results Regarding host-related factors, univariate analysis by conditional logistic regression of 687 matched pairs of cases and household controls showed that TB was associated with male sex, family history of TB, absence of a BCG scar, smoking, alcohol, anaemia, HIV infection, and history and treatment of worm infection. In a multivariable model based on 601 matched pairs, male sex, family history of TB, smoking, and HIV infection were independent risk factors of TB. The investigation of environmental factors based on the comparison of 816 cases/community control pairs showed that the risk of TB was associated with single marital status, family history of TB, adult crowding, and renting the house. In a final model assessing the combined effect of host and environmental factors, TB was associated with male sex, HIV infection, smoking (with a dose-effect relationship), history of asthma, family history of TB, marital status, adult crowding, and renting the house. Conclusion TB is a multifactorial disorder, in which environment interacts with host-related factors. This study provided useful information for the assessment of host and environmental factors of TB for the improvement of TB control activities in developing countries.	46	82	2005	10	10.1093/ije/dyi100	Public, Environmental & Occupational Health
TNF-alpha as a promising therapeutic target in chronic asthma: a lesson from rheumatoid arthritis. TNF-alpha (tumour necrosis factor-alpha) is known to play a critical role in the pathogenic mechanisms of a number of chronic inflammatory diseases, including RA (rheumatoid arthritis), Crohn's disease and psoriasis. The notion that TNF-alpha is released in allergic responses from both mast cells and macrophages via IgE-dependent mechanisms, the demonstration that elevated levels of TNF-a are frequently observed in bronchoalveolar fluid of asthmatic subjects undergoing allergen challenge and the results from exposure studies of TNF-alpha in vivo showing increases in airway responsiveness in both normal and asthmatic subjects emphasize the importance of TNF-alpha in the initiation of allergic asthmatic airway inflammation and the generation of airway hyper-responsiveness. Drugs targeting TNF-alpha have been developed to neutralize the deleterious effects of this inflammatory cytokine and have proved to be safe and effective in the treatment of patients with RA, Crohn's disease and psoriasis refractory to conventional treatments. Biological therapies blocking TNF-alpha are likely to constitute a considerable advance in the management of those difficult cases of asthma that are particularly resistant to typical treatment modalities. In this review article, we intend to address the potential role of TNF-alpha in asthma and to put forward the idea that drugs that have been developed to neutralize the deleterious effects of TNF-alpha may also be useful in the management of chronic severe asthma.. asthma| biological therapy| cytokine| inflammation| rheumatoid arthritis| tnf-alpha (turnout necrosis factor-alpha)|tumor-necrosis-factor| adhesion molecule expression| epidermal-growth-factor| lung mast-cells| nf-kappa-b| endothelial-cells| epithelial-cells| messenger-rna| smooth-muscle| in-vitro.	AUG-2005	asthma| biological therapy| cytokine| inflammation| rheumatoid arthritis| tnf-alpha (turnout necrosis factor-alpha)|tumor-necrosis-factor| adhesion molecule expression| epidermal-growth-factor| lung mast-cells| nf-kappa-b| endothelial-cells| epithelial-cells| messenger-rna| smooth-muscle| in-vitro	Russo, C; Polosa, R	TNF-alpha as a promising therapeutic target in chronic asthma: a lesson from rheumatoid arthritis		CLINICAL SCIENCE	asthma; biological therapy; cytokine; inflammation; rheumatoid arthritis; TNF-alpha (turnout necrosis factor-alpha)	TUMOR-NECROSIS-FACTOR; ADHESION MOLECULE EXPRESSION; EPIDERMAL-GROWTH-FACTOR; LUNG MAST-CELLS; NF-KAPPA-B; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; MESSENGER-RNA; SMOOTH-MUSCLE; IN-VITRO	TNF-alpha (tumour necrosis factor-alpha) is known to play a critical role in the pathogenic mechanisms of a number of chronic inflammatory diseases, including RA (rheumatoid arthritis), Crohn's disease and psoriasis. The notion that TNF-alpha is released in allergic responses from both mast cells and macrophages via IgE-dependent mechanisms, the demonstration that elevated levels of TNF-a are frequently observed in bronchoalveolar fluid of asthmatic subjects undergoing allergen challenge and the results from exposure studies of TNF-alpha in vivo showing increases in airway responsiveness in both normal and asthmatic subjects emphasize the importance of TNF-alpha in the initiation of allergic asthmatic airway inflammation and the generation of airway hyper-responsiveness. Drugs targeting TNF-alpha have been developed to neutralize the deleterious effects of this inflammatory cytokine and have proved to be safe and effective in the treatment of patients with RA, Crohn's disease and psoriasis refractory to conventional treatments. Biological therapies blocking TNF-alpha are likely to constitute a considerable advance in the management of those difficult cases of asthma that are particularly resistant to typical treatment modalities. In this review article, we intend to address the potential role of TNF-alpha in asthma and to put forward the idea that drugs that have been developed to neutralize the deleterious effects of TNF-alpha may also be useful in the management of chronic severe asthma.	65	82	2005	8		Research & Experimental Medicine
Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy. Objective. Respiratory syncytial virus (RSV) bronchiolitis is a common cause of hospitalizations in children and has been increasingly identified as a risk factor in the development of asthma. Little is known about what determines the severity of RSV bronchiolitis, which may be helpful in the initial assessment of these children. Design. We evaluated a variety of environmental and host factors that may contribute to the severity of RSV bronchiolitis in the RSV Bronchiolitis in Early Life prospective cohort study. Severity of bronchiolitis was based on the quantization of lowest O-2 saturation and the length of stay. These factors included the child's and family's demographics, presence of household allergens (dust mite, cat, dog, and cockroach), peripheral blood eosinophil count, immunoglobulin E level, infant feeding, prior illnesses, exposure to intrauterine and postnatal cigarette smoke, and family history of atopy. Patients. We prospectively enrolled 206 hospitalized infants, all under 12 months old (4.0 +/- 3.3 months old), with their first episode of severe RSV bronchiolitis (mean O-2 saturation: 91.6 +/- 7.3%; length of stay: 2.5 +/- 2.5 days; presence of radiographic opacities: 75%). Patients were excluded for a variety of reasons including previous wheezing, regular use of bronchodilator or antiinflammatory medications, any preexisting lung disease including asthma, chronic lung disease of prematurity/bronchopulmonary dysplasia, or cystic fibrosis; gastroesophageal reflux disease on medical therapy; or congenital anomalies of the chest or lung. Results. Age was found to be a significant factor in the severity of infection. The younger an infant was, the more severe the infection tended to be as measured by the lowest oxygen (O-2) saturation. We also found that infants exposed to postnatal cigarette smoke from the mother had a lower O-2 saturation than those not exposed. However, there was no significant difference in RSV bronchiolitis severity between infants exposed only to intrauterine smoke and those infants never exposed to cigarette smoke. Infants with a family history of atopy, especially a maternal history of asthma or hay fever, had a higher O-2 saturation. Although a history of maternal atopy seemed to be protective, there was no association between allergens and bronchiolitis severity, although 25% of households had elevated allergen levels. Black infants demonstrated less severe RSV bronchiolitis than their white counterparts. Multivariate analysis revealed age, race, maternal atopy, and smoking to be associated with severity of RSV bronchiolitis. Conclusion. The severity of RSV bronchiolitis early in life seems modified by postnatal maternal cigarette smoke exposure and atopy and age of the infant, not by levels of allergens in the home environment.. rsv| bronchiolitis| asthma|environmental tobacco-smoke| maternal smoking| lung-function| risk-factors| childhood asthma| mechanical ventilation| allergic sensitization| children| infection| pregnancy.	JAN-2005	rsv| bronchiolitis| asthma|environmental tobacco-smoke| maternal smoking| lung-function| risk-factors| childhood asthma| mechanical ventilation| allergic sensitization| children| infection| pregnancy	Bradley, JP; Bacharier, LB; Bonfiglio, J; Schechtman, KB; Strunk, R; Storch, G; Castro, M	Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy		PEDIATRICS	RSV; bronchiolitis; asthma	ENVIRONMENTAL TOBACCO-SMOKE; MATERNAL SMOKING; LUNG-FUNCTION; RISK-FACTORS; CHILDHOOD ASTHMA; MECHANICAL VENTILATION; ALLERGIC SENSITIZATION; CHILDREN; INFECTION; PREGNANCY	Objective. Respiratory syncytial virus (RSV) bronchiolitis is a common cause of hospitalizations in children and has been increasingly identified as a risk factor in the development of asthma. Little is known about what determines the severity of RSV bronchiolitis, which may be helpful in the initial assessment of these children. Design. We evaluated a variety of environmental and host factors that may contribute to the severity of RSV bronchiolitis in the RSV Bronchiolitis in Early Life prospective cohort study. Severity of bronchiolitis was based on the quantization of lowest O-2 saturation and the length of stay. These factors included the child's and family's demographics, presence of household allergens (dust mite, cat, dog, and cockroach), peripheral blood eosinophil count, immunoglobulin E level, infant feeding, prior illnesses, exposure to intrauterine and postnatal cigarette smoke, and family history of atopy. Patients. We prospectively enrolled 206 hospitalized infants, all under 12 months old (4.0 +/- 3.3 months old), with their first episode of severe RSV bronchiolitis (mean O-2 saturation: 91.6 +/- 7.3%; length of stay: 2.5 +/- 2.5 days; presence of radiographic opacities: 75%). Patients were excluded for a variety of reasons including previous wheezing, regular use of bronchodilator or antiinflammatory medications, any preexisting lung disease including asthma, chronic lung disease of prematurity/bronchopulmonary dysplasia, or cystic fibrosis; gastroesophageal reflux disease on medical therapy; or congenital anomalies of the chest or lung. Results. Age was found to be a significant factor in the severity of infection. The younger an infant was, the more severe the infection tended to be as measured by the lowest oxygen (O-2) saturation. We also found that infants exposed to postnatal cigarette smoke from the mother had a lower O-2 saturation than those not exposed. However, there was no significant difference in RSV bronchiolitis severity between infants exposed only to intrauterine smoke and those infants never exposed to cigarette smoke. Infants with a family history of atopy, especially a maternal history of asthma or hay fever, had a higher O-2 saturation. Although a history of maternal atopy seemed to be protective, there was no association between allergens and bronchiolitis severity, although 25% of households had elevated allergen levels. Black infants demonstrated less severe RSV bronchiolitis than their white counterparts. Multivariate analysis revealed age, race, maternal atopy, and smoking to be associated with severity of RSV bronchiolitis. Conclusion. The severity of RSV bronchiolitis early in life seems modified by postnatal maternal cigarette smoke exposure and atopy and age of the infant, not by levels of allergens in the home environment.	30	82	2005	8	10.1542/peds.2004-0059	Pediatrics
A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen. Background: Especially in childhood, sublingual immunotherapy (SLIT) could offer advantages over subcutaneous therapy. However, limited data on its efficacy is available. Methods: In four German centres 97 children (age 3-14 years) with allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective, double-blind trial comparing SLIT (Pangramin SLIT(R); ALK-SCHERAX, 0.5 mug major allergens, three times per week, 32 months) with placebo. Primary endpoint was a multiple symptom-medication score for changes in seasonal diary entries between the first and third year of the study (SLIT n = 39; placebo n = 38). Results: The multiple symptom-medication score was significantly reduced by SLIT to 77.3% of the placebo group (P = 0.0498). The subsequent analysis of the single endpoints did not reveal significant differences for symptom scores in favour of SLIT (85.1% of placebo group; P = 0.22). However, the medication score improved significantly (67.1% of placebo group; P = 0.0025). Furthermore, secondary endpoints assessing in vivo immune responses did not differ significantly between the groups. However, retrospective analysis showed some inhomogeneity for clinical and in vitro parameters at the beginning of the study. Allergic side effects with possible relation to the study drug were reported in both groups (SLIT 49%, placebo 27%, P = 0.026). Conclusion: Our study indicates that SLIT had a positive effect on the reduction of a multiple symptom-medication score, mainly by significantly reducing rescue medication use, but had no significant effect on symptoms alone in children with rhinoconjunctivitis to grass pollen compared with a placebo.. children| conjunctival provocation test| grass pollen| immunoglobulin e| immunoglobulin g(4)| rye pollen| skin prick test| specific immunotherapy| sublingual immunotherapy|standardized 5-grass-pollen extract| house-dust mite| controlled trial| swallow immunotherapy| clinical-efficacy| hay-fever| rhinitis| asthma| sensitizations.	DEC-2004	children| conjunctival provocation test| grass pollen| immunoglobulin e| immunoglobulin g(4)| rye pollen| skin prick test| specific immunotherapy| sublingual immunotherapy|standardized 5-grass-pollen extract| house-dust mite| controlled trial| swallow immunotherapy| clinical-efficacy| hay-fever| rhinitis| asthma| sensitizations	Rolinck-Werninghaus, C; Wolf, H; Liebke, C; Baars, JC; Lange, J; Kopp, MV; Hammermann, J; Leupold, W; Bartels, P; Gruebl, A; Bauer, CP; Schnitker, J; Wahn, U; Niggemann, B	A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen		ALLERGY	children; conjunctival provocation test; grass pollen; immunoglobulin E; immunoglobulin G(4); rye pollen; skin prick test; specific immunotherapy; sublingual immunotherapy	STANDARDIZED 5-GRASS-POLLEN EXTRACT; HOUSE-DUST MITE; CONTROLLED TRIAL; SWALLOW IMMUNOTHERAPY; CLINICAL-EFFICACY; HAY-FEVER; RHINITIS; ASTHMA; SENSITIZATIONS	Background: Especially in childhood, sublingual immunotherapy (SLIT) could offer advantages over subcutaneous therapy. However, limited data on its efficacy is available. Methods: In four German centres 97 children (age 3-14 years) with allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective, double-blind trial comparing SLIT (Pangramin SLIT(R); ALK-SCHERAX, 0.5 mug major allergens, three times per week, 32 months) with placebo. Primary endpoint was a multiple symptom-medication score for changes in seasonal diary entries between the first and third year of the study (SLIT n = 39; placebo n = 38). Results: The multiple symptom-medication score was significantly reduced by SLIT to 77.3% of the placebo group (P = 0.0498). The subsequent analysis of the single endpoints did not reveal significant differences for symptom scores in favour of SLIT (85.1% of placebo group; P = 0.22). However, the medication score improved significantly (67.1% of placebo group; P = 0.0025). Furthermore, secondary endpoints assessing in vivo immune responses did not differ significantly between the groups. However, retrospective analysis showed some inhomogeneity for clinical and in vitro parameters at the beginning of the study. Allergic side effects with possible relation to the study drug were reported in both groups (SLIT 49%, placebo 27%, P = 0.026). Conclusion: Our study indicates that SLIT had a positive effect on the reduction of a multiple symptom-medication score, mainly by significantly reducing rescue medication use, but had no significant effect on symptoms alone in children with rhinoconjunctivitis to grass pollen compared with a placebo.	34	82	2004	9	10.1111/j.1398-9995.2004.00627.x	Allergy; Immunology
Indoor air pollution and airway disease. Scientific interest in indoor pollution has been increasing since the second half of the 1980s. Growing scientific evidence has shown that because people generally spend the majority of their time indoors, indoor pollution plays a significant role in affecting health and is thus an important health issue. Indoor environments include dwellings, workplaces, schools and day care centres, bars, discotheques and vehicles. Common indoor pollutants are environmental tobacco smoke, particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and biological allergens. In developing countries, relevant sources of indoor pollution include biomass and coal burning for cooking and heating. Concentrations of these pollutants can be many times higher indoors than outdoors. Indoor air pollution may increase the risk of irritation phenomena, allergic sensitisation, acute and chronic respiratory disorders and lung function impairment. Recent conservative estimates have shown that 1.5-2 million deaths per year worldwide could be attributed to indoor air pollution. Approximately I million of these deaths occur in children aged tinder 5 years due to acute respiratory infections and significant proportions of deaths occur due to chronic obstructive pulmonary disease and lung cancer in women. Today, indoor air pollution ranks tenth among preventable risk factors contributing to the global burden of disease. Further research is necessary to better evaluate the respiratory health effects of indoor pollution and to implement protective programmes for public health.. indoor pollution| biomass| ets| particles| nitrogen oxides| voc| epidemiology| asthma| copd| respiratory health| prevention|volatile organic-compounds| environmental tobacco-smoke| exposure assessment survey| respiratory health survey| noncancer end-points| developing-countries| bronchial responsiveness| particulate matter| pulmonary-function| childhood asthma.	DEC-2004	indoor pollution| biomass| ets| particles| nitrogen oxides| voc| epidemiology| asthma| copd| respiratory health| prevention|volatile organic-compounds| environmental tobacco-smoke| exposure assessment survey| respiratory health survey| noncancer end-points| developing-countries| bronchial responsiveness| particulate matter| pulmonary-function| childhood asthma	Viegi, G; Simoni, M; Scognamiglio, A; Baldacci, S; Pistelli, F; Carrozzi, L; Annesi-Maesano, I	Indoor air pollution and airway disease		INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE	indoor pollution; biomass; ETS; particles; nitrogen oxides; VOC; epidemiology; asthma; COPD; respiratory health; prevention	VOLATILE ORGANIC-COMPOUNDS; ENVIRONMENTAL TOBACCO-SMOKE; EXPOSURE ASSESSMENT SURVEY; RESPIRATORY HEALTH SURVEY; NONCANCER END-POINTS; DEVELOPING-COUNTRIES; BRONCHIAL RESPONSIVENESS; PARTICULATE MATTER; PULMONARY-FUNCTION; CHILDHOOD ASTHMA	Scientific interest in indoor pollution has been increasing since the second half of the 1980s. Growing scientific evidence has shown that because people generally spend the majority of their time indoors, indoor pollution plays a significant role in affecting health and is thus an important health issue. Indoor environments include dwellings, workplaces, schools and day care centres, bars, discotheques and vehicles. Common indoor pollutants are environmental tobacco smoke, particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and biological allergens. In developing countries, relevant sources of indoor pollution include biomass and coal burning for cooking and heating. Concentrations of these pollutants can be many times higher indoors than outdoors. Indoor air pollution may increase the risk of irritation phenomena, allergic sensitisation, acute and chronic respiratory disorders and lung function impairment. Recent conservative estimates have shown that 1.5-2 million deaths per year worldwide could be attributed to indoor air pollution. Approximately I million of these deaths occur in children aged tinder 5 years due to acute respiratory infections and significant proportions of deaths occur due to chronic obstructive pulmonary disease and lung cancer in women. Today, indoor air pollution ranks tenth among preventable risk factors contributing to the global burden of disease. Further research is necessary to better evaluate the respiratory health effects of indoor pollution and to implement protective programmes for public health.	126	82	2004	15		Infectious Diseases; Respiratory System
Summary of human responses to ventilation. It is known that ventilation is necessary to remove indoor-generated pollutants from indoor air or dilute their concentration to acceptable levels. But as the limit values of all pollutants are not known the exact determination of required ventilation rates based on pollutant concentrations is seldom possible. The selection of ventilation rates has to be based also on epidemiological research, laboratory and field experiments and experience. The existing literature indicates that ventilation has a significant impact on several important human outcomes including: (1) communicable respiratory illnesses; (2) sick building syndrome symptoms; (3) task performance and productivity, and (4) perceived air quality (PAQ) among occupants or sensory panels (5) respiratory allergies and asthma. In many studies, prevalence of sick building syndrome symptoms has also been associated with characteristics of HVAC-systems. Often the prevalence of SBS symptoms is higher in air-conditioned buildings than in naturally ventilated buildings. The evidence suggests that better hygiene, commissioning, operation and maintenance of air handling systems may be particularly important for reducing the negative effects of HVAC systems. Ventilation may also have harmful effects on indoor air quality and climate if not properly designed, installed, maintained and operated. Ventilation may bring indoors harmful substances or deteriorate indoor environment. Ventilation interacts also with the building envelope and may deteriorate the structures of the building. Ventilation changes the pressure differences across the structures of building and may cause or prevent infiltration of pollutants from structures or adjacent spaces. Ventilation is also in many cases used to control the thermal environment or humidity in buildings. The paper summarises the current knowledge on positive and negative effects of ventilation on health and other human responses. The focus is on office-type working environment and residential buildings.. ventilation| ventilation rate| hvac-system sbs symptoms| productivity| sick leave| co2| air-conditioning| infectious disease| cleanliness|indoor air-quality| sick building syndrome| house-dust mites| mechanical ventilation| office environment| aerosol fraction| sbs symptoms| health| pollen| pollution.	AUG-2004	ventilation| ventilation rate| hvac-system sbs symptoms| productivity| sick leave| co2| air-conditioning| infectious disease| cleanliness|indoor air-quality| sick building syndrome| house-dust mites| mechanical ventilation| office environment| aerosol fraction| sbs symptoms| health| pollen| pollution	Seppanen, OA; Fisk, WJ	Summary of human responses to ventilation		INDOOR AIR	ventilation; ventilation rate; HVAC-system SBS symptoms; productivity; sick leave; CO2; air-conditioning; infectious disease; cleanliness	INDOOR AIR-QUALITY; SICK BUILDING SYNDROME; HOUSE-DUST MITES; MECHANICAL VENTILATION; OFFICE ENVIRONMENT; AEROSOL FRACTION; SBS SYMPTOMS; HEALTH; POLLEN; POLLUTION	It is known that ventilation is necessary to remove indoor-generated pollutants from indoor air or dilute their concentration to acceptable levels. But as the limit values of all pollutants are not known the exact determination of required ventilation rates based on pollutant concentrations is seldom possible. The selection of ventilation rates has to be based also on epidemiological research, laboratory and field experiments and experience. The existing literature indicates that ventilation has a significant impact on several important human outcomes including: (1) communicable respiratory illnesses; (2) sick building syndrome symptoms; (3) task performance and productivity, and (4) perceived air quality (PAQ) among occupants or sensory panels (5) respiratory allergies and asthma. In many studies, prevalence of sick building syndrome symptoms has also been associated with characteristics of HVAC-systems. Often the prevalence of SBS symptoms is higher in air-conditioned buildings than in naturally ventilated buildings. The evidence suggests that better hygiene, commissioning, operation and maintenance of air handling systems may be particularly important for reducing the negative effects of HVAC systems. Ventilation may also have harmful effects on indoor air quality and climate if not properly designed, installed, maintained and operated. Ventilation may bring indoors harmful substances or deteriorate indoor environment. Ventilation interacts also with the building envelope and may deteriorate the structures of the building. Ventilation changes the pressure differences across the structures of building and may cause or prevent infiltration of pollutants from structures or adjacent spaces. Ventilation is also in many cases used to control the thermal environment or humidity in buildings. The paper summarises the current knowledge on positive and negative effects of ventilation on health and other human responses. The focus is on office-type working environment and residential buildings.	81	82	2004	17	10.1111/j.1600-0668.2004.00279.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Airway inflammation in chronic obstructive pulmonary disease: Comparisons with asthma. Chronic obstructive pulmonary disease (COPD) is a progressive syndrome of expiratory airflow limitation caused by chronic inflammation of the airways and lung parenchyma. The airway inflammatory response in COPD is initiated by smoking in the overwhelming majority of cases, and chronic exposure to cigarette smoke initiates a series of events that causes damage to central airways, peripheral airways, and terminal airspaces, leading to physiologic and clinical abnormalities. Although COPD shares some clinical features with asthma, another prevalent airway inflammatory disease, there are distinct differences in the phenotypic characteristics of airway inflammation between COPD and asthma. The eosinophil is the most prominent inflammatory cell in asthma, with mast cells, lymphocytes, and macrophages playing important but less prominent roles. In COPD the cellular composition of the airway inflammatory infiltrate differs, with neutrophils, macrophages, and lymphocytes assuming prominence and the eosinophil playing a minor role, except in the setting of exacerbations. The contrasting inflammatory phenotypes of asthma and COPD have important implications for clinical and physiologic manifestations of disease, as well as for therapy.. inflammation| chronic obstructive pulmonary disease| small airway| asthma| lymphocyte|chronic-bronchitis| peripheral airways| lung-function| macrophage metalloelastase| structural-changes| cigarette smokers| flow obstruction| alveolar tissue| t-lymphocytes| emphysema.	NOV-2003	inflammation| chronic obstructive pulmonary disease| small airway| asthma| lymphocyte|chronic-bronchitis| peripheral airways| lung-function| macrophage metalloelastase| structural-changes| cigarette smokers| flow obstruction| alveolar tissue| t-lymphocytes| emphysema	Sutherland, ER; Martin, RJ	Airway inflammation in chronic obstructive pulmonary disease: Comparisons with asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	inflammation; chronic obstructive pulmonary disease; small airway; asthma; lymphocyte	CHRONIC-BRONCHITIS; PERIPHERAL AIRWAYS; LUNG-FUNCTION; MACROPHAGE METALLOELASTASE; STRUCTURAL-CHANGES; CIGARETTE SMOKERS; FLOW OBSTRUCTION; ALVEOLAR TISSUE; T-LYMPHOCYTES; EMPHYSEMA	Chronic obstructive pulmonary disease (COPD) is a progressive syndrome of expiratory airflow limitation caused by chronic inflammation of the airways and lung parenchyma. The airway inflammatory response in COPD is initiated by smoking in the overwhelming majority of cases, and chronic exposure to cigarette smoke initiates a series of events that causes damage to central airways, peripheral airways, and terminal airspaces, leading to physiologic and clinical abnormalities. Although COPD shares some clinical features with asthma, another prevalent airway inflammatory disease, there are distinct differences in the phenotypic characteristics of airway inflammation between COPD and asthma. The eosinophil is the most prominent inflammatory cell in asthma, with mast cells, lymphocytes, and macrophages playing important but less prominent roles. In COPD the cellular composition of the airway inflammatory infiltrate differs, with neutrophils, macrophages, and lymphocytes assuming prominence and the eosinophil playing a minor role, except in the setting of exacerbations. The contrasting inflammatory phenotypes of asthma and COPD have important implications for clinical and physiologic manifestations of disease, as well as for therapy.	42	82	2003	9	10.1067/mai.2003.1760	Allergy; Immunology
Antibiotics in dust originating from a pig-fattening farm: A new source of health hazard for farmers?. Pig-house dust originates from feed, bedding, feces, and the animals themselves. If the animals receive drugs such as antibiotics, residues of these substances may occur in manure, in the air, or on surfaces of the respective animal house. In a retrospective study, we investigated dust samples collected during two decades from the same piggery for the occurrence of various antibiotics. In 90% of these samples, we detected up to five different antibiotics, including tylosin, various tetra-cyclines, sulfamethazine, and chloramphenicol, in total amounts up to 12.5 mg/kg dust. High dust exposure in animal confinement buildings is believed to be a respiratory health hazard because of the high content of microorganisms, endotoxins, and allergens. Further risks may arise from the inhalation of dust contaminated with a cocktail of antibiotics. Apart from that, our data provide first evidence for a new route of entry for veterinary drugs in the environment.. antibiotics| dust| farmer| liquid chromatography| mass spectrometry| pig fattening| veterinary drugs|allergic contact-dermatitis| livestock buildings| liquid manure| environment| pharmaceuticals| contaminants| substances| pollutants| emissions| residues.	OCT-2003	antibiotics| dust| farmer| liquid chromatography| mass spectrometry| pig fattening| veterinary drugs|allergic contact-dermatitis| livestock buildings| liquid manure| environment| pharmaceuticals| contaminants| substances| pollutants| emissions| residues	Hamscher, G; Pawelzick, HT; Sczesny, S; Nau, H; Hartung, J	Antibiotics in dust originating from a pig-fattening farm: A new source of health hazard for farmers?		ENVIRONMENTAL HEALTH PERSPECTIVES	antibiotics; dust; farmer; liquid chromatography; mass spectrometry; pig fattening; veterinary drugs	ALLERGIC CONTACT-DERMATITIS; LIVESTOCK BUILDINGS; LIQUID MANURE; ENVIRONMENT; PHARMACEUTICALS; CONTAMINANTS; SUBSTANCES; POLLUTANTS; EMISSIONS; RESIDUES	Pig-house dust originates from feed, bedding, feces, and the animals themselves. If the animals receive drugs such as antibiotics, residues of these substances may occur in manure, in the air, or on surfaces of the respective animal house. In a retrospective study, we investigated dust samples collected during two decades from the same piggery for the occurrence of various antibiotics. In 90% of these samples, we detected up to five different antibiotics, including tylosin, various tetra-cyclines, sulfamethazine, and chloramphenicol, in total amounts up to 12.5 mg/kg dust. High dust exposure in animal confinement buildings is believed to be a respiratory health hazard because of the high content of microorganisms, endotoxins, and allergens. Further risks may arise from the inhalation of dust contaminated with a cocktail of antibiotics. Apart from that, our data provide first evidence for a new route of entry for veterinary drugs in the environment.	32	82	2003	5	10.1289/ehp.6288	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
The transfer of immunity from mother to child. The newborn's immune system grows fast from a small size at birth by exposure primarily to the intestinal microflora normally obtained from the mother at and after birth. While building up its immune system, the infant is supported by the transplacental IgG antibodies, which also contain anti-idiotypic antibodies, possibly also actively priming the offspring. The second mode of transfer of immunity occurs via the milk. Numerous major protective components, including secretory IgA (SIgA) antibodies and lactoferrin, are present. The breastfed infant is better protected against numerous common infections than the non-breastfed. Breastfeeding also seems to actively stimulate the infant's immune system by anti-idiotypes, uptake of milk lymphocytes, cytokines, etc. Therefore, the breastfed child continues to be better protected against various infections for some years. Vaccine responses are also often enhanced in breastfed infants. Long-lasting protection against certain immunological diseases such as allergies and celiac disease is also noted.. anti-idiotypic| secretory iga| lactoferrin| bramwell receptor| immune system| breastfeeding|breast-fed infants| antibody-response| human-milk| igg antibodies| mice| protection| diarrhea| cells| colonization| immunization.	2003	anti-idiotypic| secretory iga| lactoferrin| bramwell receptor| immune system| breastfeeding|breast-fed infants| antibody-response| human-milk| igg antibodies| mice| protection| diarrhea| cells| colonization| immunization	Hanson, LA; Korotkova, M; Lundin, S; Haversen, L; Silfverdal, SA; Mattsby-Baltzer, I; Strandvik, B; Telemo, E	The transfer of immunity from mother to child		IMMUNE MECHANISMS AND DISEASE	anti-idiotypic; secretory IgA; lactoferrin; Bramwell receptor; immune system; breastfeeding	BREAST-FED INFANTS; ANTIBODY-RESPONSE; HUMAN-MILK; IGG ANTIBODIES; MICE; PROTECTION; DIARRHEA; CELLS; COLONIZATION; IMMUNIZATION	The newborn's immune system grows fast from a small size at birth by exposure primarily to the intestinal microflora normally obtained from the mother at and after birth. While building up its immune system, the infant is supported by the transplacental IgG antibodies, which also contain anti-idiotypic antibodies, possibly also actively priming the offspring. The second mode of transfer of immunity occurs via the milk. Numerous major protective components, including secretory IgA (SIgA) antibodies and lactoferrin, are present. The breastfed infant is better protected against numerous common infections than the non-breastfed. Breastfeeding also seems to actively stimulate the infant's immune system by anti-idiotypes, uptake of milk lymphocytes, cytokines, etc. Therefore, the breastfed child continues to be better protected against various infections for some years. Vaccine responses are also often enhanced in breastfed infants. Long-lasting protection against certain immunological diseases such as allergies and celiac disease is also noted.	60	82	2003	8		Cell Biology; Immunology; Science & Technology - Other Topics
Studies on the autoxidation and sensitizing capacity of the fragrance chemical linalool, identifying a linalool hydroperoxide. Fragrances are among the most common causes of allergic contact dermatitis. The two monoterpenes linalool and d -limonene are the most frequently incorporated fragrance chemicals in scented products. Previous studies on d -limonene show that this monoterpene oxidizes on air exposure (autoxidation) and that allergenic oxidation products are formed. Due to structural similarities, linalool might also form allergenic oxidation products on air exposure. The aim of the present study was to study the autoxidation of linalool and to investigate the sensitizing potential of linalool before and after air exposure. Linalool was oxidized for 10 weeks and gas chromatographic analyses showed that the content of linalool decreased to about 80%. The chromatograms revealed the formation of other compounds during oxidation. One of the major oxidation products was isolated and identified as 7-hydroperoxy-3,7-dimethyl-octa-1,5-diene-3-ol. This substance is, to the best of our knowledge, described for the first time. In sensitization studies in guinea pigs, linalool of high purity gave no reactions, while linalool that had been oxidized for 10 weeks sensitized the animals. It is concluded that autoxidation of linalool is essential for its sensitizing potential.. autoxidation| fragrance allergy| fcat| gas chromatographic analysis| guinea pigs| hydroperoxide| linalool| nmr| sensitization studies| terpene|oxidized d-limonene| contact allergens| 15-hydroperoxyabietic acid| citrus solvent| essential oils| colophony| dermatitis.	MAY-2002	autoxidation| fragrance allergy| fcat| gas chromatographic analysis| guinea pigs| hydroperoxide| linalool| nmr| sensitization studies| terpene|oxidized d-limonene| contact allergens| 15-hydroperoxyabietic acid| citrus solvent| essential oils| colophony| dermatitis	Skold, M; Borje, A; Matura, M; Karlberg, AT	Studies on the autoxidation and sensitizing capacity of the fragrance chemical linalool, identifying a linalool hydroperoxide		CONTACT DERMATITIS	autoxidation; fragrance allergy; FCAT; gas chromatographic analysis; guinea pigs; hydroperoxide; linalool; NMR; sensitization studies; terpene	OXIDIZED D-LIMONENE; CONTACT ALLERGENS; 15-HYDROPEROXYABIETIC ACID; CITRUS SOLVENT; ESSENTIAL OILS; COLOPHONY; DERMATITIS	Fragrances are among the most common causes of allergic contact dermatitis. The two monoterpenes linalool and d -limonene are the most frequently incorporated fragrance chemicals in scented products. Previous studies on d -limonene show that this monoterpene oxidizes on air exposure (autoxidation) and that allergenic oxidation products are formed. Due to structural similarities, linalool might also form allergenic oxidation products on air exposure. The aim of the present study was to study the autoxidation of linalool and to investigate the sensitizing potential of linalool before and after air exposure. Linalool was oxidized for 10 weeks and gas chromatographic analyses showed that the content of linalool decreased to about 80%. The chromatograms revealed the formation of other compounds during oxidation. One of the major oxidation products was isolated and identified as 7-hydroperoxy-3,7-dimethyl-octa-1,5-diene-3-ol. This substance is, to the best of our knowledge, described for the first time. In sensitization studies in guinea pigs, linalool of high purity gave no reactions, while linalool that had been oxidized for 10 weeks sensitized the animals. It is concluded that autoxidation of linalool is essential for its sensitizing potential.	27	82	2002	6	10.1034/j.1600-0536.2002.460504.x	Allergy; Dermatology
A controlled trial of an environmental tobacco smoke reduction intervention in low-income children with asthma. Study objectives: To determine the effectiveness of a cotinine-feedback, behaviorally based education intervention in reducing environmental tobacco smoke (ETS) exposure and health-care utilization of children with asthma. Design: Randomized controlled trial of educational intervention vs usual care. Setting: The pediatric pulmonary service of a regional pediatric hospital. Participants: ETS-exposed, Medicaid/Niedi-Cal-eligible, predominantly minority children who were 3 to 12 years old and who were seen for asthma in the hospital's emergency, inpatient, and outpatient services departments (n = 87). Intervention: Three nurse-led sessions employing behavior-changing strategies and basic asthma education and that incorporated repeated feedback on the child's urinary cotinine level. Measurements: The primary measurements were the urinary cotinine/creatinine ratio (CCR) and the number of acute asthma medical visits. The secondary measurements were number of hospitalizations, smoking restrictions in home, amount smoked, reported exposures of children, and asthma control. Results: The intervention was associated with a significantly lower odds ratio (OR) for more than one acute asthma medical visit in the follow-up year, after adjusting for baseline visits (total visits, 87; OR, 0.32; p = 0.03), and a comparably sized but nonsignificant OR for one or more hospitalization (OR, 0.34; p = 0.14). The follow-up CCR measurement and the determination of whether smoking was prohibited inside the home strongly favored the intervention group (n = 51) (mean difference in CCR adjusted for baseline, -0.38; p = 0.26; n = 51) (60; OR [for proportion of subjects prohibiting smoking], 0.24; p = 0.11; n = 60). Conclusions: This intervention significantly reduced asthma health-care utilization in ETS-exposed, low-income, minority children. Effects sizes for urine cotinine and proportion prohibiting smoking were moderate to large but not statistically significant, possibly the result of reduced precision due to the loss of patients to active follow-up. Improving ETS reduction interventions and understanding their mechanism of action on asthma outcomes requires further controlled trials that measure ETS exposure and behavioral and disease outcomes concurrently.. asthma| behavior change| children| controlled trial| cotinine| education| environmental tobacco smoke| low-income|cotinine-assisted intervention| passive smoking| relapse prevention| young-children| body-fluids| exposure| pregnancy| program| parents| postpartum.	NOV-2001	asthma| behavior change| children| controlled trial| cotinine| education| environmental tobacco smoke| low-income|cotinine-assisted intervention| passive smoking| relapse prevention| young-children| body-fluids| exposure| pregnancy| program| parents| postpartum	Wilson, SR; Yamada, EG; Sudhakar, R; Roberto, L; Mannino, D; Mejia, C; Huss, N	A controlled trial of an environmental tobacco smoke reduction intervention in low-income children with asthma		CHEST	asthma; behavior change; children; controlled trial; cotinine; education; environmental tobacco smoke; low-income	COTININE-ASSISTED INTERVENTION; PASSIVE SMOKING; RELAPSE PREVENTION; YOUNG-CHILDREN; BODY-FLUIDS; EXPOSURE; PREGNANCY; PROGRAM; PARENTS; POSTPARTUM	Study objectives: To determine the effectiveness of a cotinine-feedback, behaviorally based education intervention in reducing environmental tobacco smoke (ETS) exposure and health-care utilization of children with asthma. Design: Randomized controlled trial of educational intervention vs usual care. Setting: The pediatric pulmonary service of a regional pediatric hospital. Participants: ETS-exposed, Medicaid/Niedi-Cal-eligible, predominantly minority children who were 3 to 12 years old and who were seen for asthma in the hospital's emergency, inpatient, and outpatient services departments (n = 87). Intervention: Three nurse-led sessions employing behavior-changing strategies and basic asthma education and that incorporated repeated feedback on the child's urinary cotinine level. Measurements: The primary measurements were the urinary cotinine/creatinine ratio (CCR) and the number of acute asthma medical visits. The secondary measurements were number of hospitalizations, smoking restrictions in home, amount smoked, reported exposures of children, and asthma control. Results: The intervention was associated with a significantly lower odds ratio (OR) for more than one acute asthma medical visit in the follow-up year, after adjusting for baseline visits (total visits, 87; OR, 0.32; p = 0.03), and a comparably sized but nonsignificant OR for one or more hospitalization (OR, 0.34; p = 0.14). The follow-up CCR measurement and the determination of whether smoking was prohibited inside the home strongly favored the intervention group (n = 51) (mean difference in CCR adjusted for baseline, -0.38; p = 0.26; n = 51) (60; OR [for proportion of subjects prohibiting smoking], 0.24; p = 0.11; n = 60). Conclusions: This intervention significantly reduced asthma health-care utilization in ETS-exposed, low-income, minority children. Effects sizes for urine cotinine and proportion prohibiting smoking were moderate to large but not statistically significant, possibly the result of reduced precision due to the loss of patients to active follow-up. Improving ETS reduction interventions and understanding their mechanism of action on asthma outcomes requires further controlled trials that measure ETS exposure and behavioral and disease outcomes concurrently.	42	82	2001	14	10.1378/chest.120.5.1709	General & Internal Medicine; Respiratory System
Prenatal exposure, maternal sensitization,, and sensitization in utero to indoor allergens in an inner-city cohort. Primary sensitization to antigens may occur prenatally. We hypothesized that high prenatal exposure to indoor antigens increases the risk for sensitization in newborns in New York City populations with increased risk for asthma. We also investigated whether maternal sensitization is required for in utero sensitization to occur. One hundred sixty-seven pregnant African American or Dominican women residing in northern Manhattan were recruited and antigen was measured from home dust. After delivery, newborn cord and maternal blood were assayed for IgE and mononuclear cell proliferation and cytokine production in response to antigen. Cockroach, mouse, but not dust mite antigens, were commonly elevated in the kitchens and pregnant mothers' beds. Increased mononuclear cell proliferation occurred in 54% of newborns in response to cockroach, 25% in response to dust mite Dermatophagoides pteronyssinus, 40% in response to dust mite D. farinae, and 34% in response to mouse protein extracts. Antigen-induced mononuclear cell proliferation occurred in cord blood even in the absence of antigen-induced mononuclear cell proliferation in the mother. Proliferation in response to antigens did not correlate with IgE levels, but proliferation in response to dust mite extracts correlated with interluekin-5 (IL-5) production in cord blood. These results suggest that (1) high prenatal exposures to cockroach and mouse antigens are prevalent; (2) in utero sensitization to multiple indoor antigens is common, occurs to a different degree than maternal sensitization, and may involve IL-5 uprequlation.. in utero sensitization| indoor antigens| lymphocyte proliferation|house-dust mite| t-cell responses| der-p-i| dermatophagoides-pteronyssinus| environmental allergens| asthma| children| life| cockroach| ige.	SEP 15-2001	in utero sensitization| indoor antigens| lymphocyte proliferation|house-dust mite| t-cell responses| der-p-i| dermatophagoides-pteronyssinus| environmental allergens| asthma| children| life| cockroach| ige	Miller, RL; Chew, GL; Bell, CA; Biedermann, SA; Aggarwal, M; Kinney, PL; Tsai, WY; Whyatt, RM; Perera, FP; Ford, JG	Prenatal exposure, maternal sensitization,, and sensitization in utero to indoor allergens in an inner-city cohort		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	in utero sensitization; indoor antigens; lymphocyte proliferation	HOUSE-DUST MITE; T-CELL RESPONSES; DER-P-I; DERMATOPHAGOIDES-PTERONYSSINUS; ENVIRONMENTAL ALLERGENS; ASTHMA; CHILDREN; LIFE; COCKROACH; IGE	Primary sensitization to antigens may occur prenatally. We hypothesized that high prenatal exposure to indoor antigens increases the risk for sensitization in newborns in New York City populations with increased risk for asthma. We also investigated whether maternal sensitization is required for in utero sensitization to occur. One hundred sixty-seven pregnant African American or Dominican women residing in northern Manhattan were recruited and antigen was measured from home dust. After delivery, newborn cord and maternal blood were assayed for IgE and mononuclear cell proliferation and cytokine production in response to antigen. Cockroach, mouse, but not dust mite antigens, were commonly elevated in the kitchens and pregnant mothers' beds. Increased mononuclear cell proliferation occurred in 54% of newborns in response to cockroach, 25% in response to dust mite Dermatophagoides pteronyssinus, 40% in response to dust mite D. farinae, and 34% in response to mouse protein extracts. Antigen-induced mononuclear cell proliferation occurred in cord blood even in the absence of antigen-induced mononuclear cell proliferation in the mother. Proliferation in response to antigens did not correlate with IgE levels, but proliferation in response to dust mite extracts correlated with interluekin-5 (IL-5) production in cord blood. These results suggest that (1) high prenatal exposures to cockroach and mouse antigens are prevalent; (2) in utero sensitization to multiple indoor antigens is common, occurs to a different degree than maternal sensitization, and may involve IL-5 uprequlation.	41	82	2001	7		General & Internal Medicine; Respiratory System
Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation. Lung epithelial cells can influence immune responses to airway allergens(1,2). Airway epithelial cells also undergo apoptosis after encountering environmental allergens(3); yet, relatively little is known about how these are cleared, and their effect on airway inflammation. Here we show that airway epithelial cells efficiently engulf apoptotic epithelial cells and secrete anti-inflammatory cytokines, dependent upon intracellular signalling by the small GTPase Rac1. Inducible deletion of Rac1 expression specifically in airway epithelial cells in a mouse model resulted in defective engulfment by epithelial cells and aberrant anti-inflammatory cytokine production. Intranasal priming and challenge of these mice with house dust mite extract or ovalbumin as allergens led to exacerbated inflammation, augmented Th2 cytokines and airway hyper-responsiveness, with decreased interleukin (IL)-10 in bronchial lavages. Rac1-deficient epithelial cells produced much higher IL-33 upon allergen or apoptotic cell encounter, with increased numbers of nuocyte-like cells(1,4,5). Administration of exogenous IL-10 'rescued' the airway inflammation phenotype in Rac1-deficient mice, with decreased IL-33. Collectively, these genetic and functional studies suggest a new role for Rac1-dependent engulfment by airway epithelial cells and in establishing the anti-inflammatory environment, and that defects in cell clearance in the airways could contribute to inflammatory responses towards common allergens.. dust mite allergen| asthma| responses| family| engulfment| mechanism| mimicry| protein| innate| mouse.	JAN 24-2013	dust mite allergen| asthma| responses| family| engulfment| mechanism| mimicry| protein| innate| mouse	Juncadella, IJ; Kadl, A; Sharma, AK; Shim, YM; Hochreiter-Hufford, A; Borish, L; Ravichandran, KS	Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation		NATURE		DUST MITE ALLERGEN; ASTHMA; RESPONSES; FAMILY; ENGULFMENT; MECHANISM; MIMICRY; PROTEIN; INNATE; MOUSE	Lung epithelial cells can influence immune responses to airway allergens(1,2). Airway epithelial cells also undergo apoptosis after encountering environmental allergens(3); yet, relatively little is known about how these are cleared, and their effect on airway inflammation. Here we show that airway epithelial cells efficiently engulf apoptotic epithelial cells and secrete anti-inflammatory cytokines, dependent upon intracellular signalling by the small GTPase Rac1. Inducible deletion of Rac1 expression specifically in airway epithelial cells in a mouse model resulted in defective engulfment by epithelial cells and aberrant anti-inflammatory cytokine production. Intranasal priming and challenge of these mice with house dust mite extract or ovalbumin as allergens led to exacerbated inflammation, augmented Th2 cytokines and airway hyper-responsiveness, with decreased interleukin (IL)-10 in bronchial lavages. Rac1-deficient epithelial cells produced much higher IL-33 upon allergen or apoptotic cell encounter, with increased numbers of nuocyte-like cells(1,4,5). Administration of exogenous IL-10 'rescued' the airway inflammation phenotype in Rac1-deficient mice, with decreased IL-33. Collectively, these genetic and functional studies suggest a new role for Rac1-dependent engulfment by airway epithelial cells and in establishing the anti-inflammatory environment, and that defects in cell clearance in the airways could contribute to inflammatory responses towards common allergens.	30	81	2013	7	10.1038/nature11714	Science & Technology - Other Topics
IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization. Background: Allergen exposure at lung and gut mucosae can lead to aberrant T(H)2 immunity and allergic disease. The epithelium-associated cytokines thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 are suggested to be important for the initiation of these responses. Objective: We sought to investigate the contributions of TSLP, IL-25, and IL-33 in the development of allergic disease to the common allergens house dust mite (HDM) or peanut. Methods: Neutralizing antibodies or mice deficient in TSLP, IL-25, or IL-33 signaling were exposed to HDM intranasally or peanut intragastrically, and immune inflammatory and physiologic responses were evaluated. In vitro assays were performed to examine specific dendritic cell (DC) functions. Results: We showed that experimental HDM-induced allergic asthma and food allergy and anaphylaxis to peanut were associated with TSLP production but developed independently of TSLP, likely because these allergens functionally mimicked TSLP inhibition of IL-12 production and induction of OX40 ligand (OX40L) on DCs. Blockade of OX40L significantly lessened allergic responses to HDM or peanut. Although IL-25 and IL-33 induced OX40L on DCs in vitro, only IL-33 signaling was necessary for intact allergic immunity, likely because of its superior ability to induce DC OX40L and expand innate lymphoid cells in vivo. Conclusion: These data identify a nonredundant, IL-33-driven mechanism initiating T(H)2 responses to the clinically relevant allergens HDM and peanut. Our findings, along with those in infectious and transgenic/surrogate allergen systems, favor a paradigm whereby multiple molecular pathways can initiate T(H)2 immunity, which has implications for the conceptualization and manipulation of these responses in health and disease. (J Allergy Clin Immunol 2013;131:187-200.). t(h)2| allergy| asthma| house dust mite| peanut| thymic stromal lymphopoietin| il-25| il-33| ox40 ligand| innate lymphoid cells|airway inflammation| dendritic cells| immune-responses| in-vivo| th2 responses| ox40 ligand| tslp| asthma| receptor| innate.	JAN-2013	t(h)2| allergy| asthma| house dust mite| peanut| thymic stromal lymphopoietin| il-25| il-33| ox40 ligand| innate lymphoid cells|airway inflammation| dendritic cells| immune-responses| in-vivo| th2 responses| ox40 ligand| tslp| asthma| receptor| innate	Chu, DK; Llop-Guevara, A; Walker, TD; Flader, K; Goncharova, S; Boudreau, JE; Moore, CL; In, TS; Waserman, S; Coyle, AJ; Kolbeck, R; Humbles, AA; Jordana, M	IL-33, but not thymic stromal lymphopoietin or IL-25, is central to mite and peanut allergic sensitization		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	T(H)2; allergy; asthma; house dust mite; peanut; thymic stromal lymphopoietin; IL-25; IL-33; OX40 ligand; innate lymphoid cells	AIRWAY INFLAMMATION; DENDRITIC CELLS; IMMUNE-RESPONSES; IN-VIVO; TH2 RESPONSES; OX40 LIGAND; TSLP; ASTHMA; RECEPTOR; INNATE	Background: Allergen exposure at lung and gut mucosae can lead to aberrant T(H)2 immunity and allergic disease. The epithelium-associated cytokines thymic stromal lymphopoietin (TSLP), IL-25, and IL-33 are suggested to be important for the initiation of these responses. Objective: We sought to investigate the contributions of TSLP, IL-25, and IL-33 in the development of allergic disease to the common allergens house dust mite (HDM) or peanut. Methods: Neutralizing antibodies or mice deficient in TSLP, IL-25, or IL-33 signaling were exposed to HDM intranasally or peanut intragastrically, and immune inflammatory and physiologic responses were evaluated. In vitro assays were performed to examine specific dendritic cell (DC) functions. Results: We showed that experimental HDM-induced allergic asthma and food allergy and anaphylaxis to peanut were associated with TSLP production but developed independently of TSLP, likely because these allergens functionally mimicked TSLP inhibition of IL-12 production and induction of OX40 ligand (OX40L) on DCs. Blockade of OX40L significantly lessened allergic responses to HDM or peanut. Although IL-25 and IL-33 induced OX40L on DCs in vitro, only IL-33 signaling was necessary for intact allergic immunity, likely because of its superior ability to induce DC OX40L and expand innate lymphoid cells in vivo. Conclusion: These data identify a nonredundant, IL-33-driven mechanism initiating T(H)2 responses to the clinically relevant allergens HDM and peanut. Our findings, along with those in infectious and transgenic/surrogate allergen systems, favor a paradigm whereby multiple molecular pathways can initiate T(H)2 immunity, which has implications for the conceptualization and manipulation of these responses in health and disease. (J Allergy Clin Immunol 2013;131:187-200.)	63	81	2013	22	10.1016/j.jaci.2012.08.002	Allergy; Immunology
Persistence of multiple illnesses in World Trade Center rescue and recovery workers: a cohort study. Background More than 50000 people participated in the rescue and recovery work that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC). Multiple health problems in these workers were reported in the early years after the disaster. We report incidence and prevalence rates of physical and mental health disorders during the 9 years since the attacks, examine their associations with occupational exposures, and quantify physical and mental health comorbidities. Methods In this longitudinal study of a large cohort of WTC rescue and recovery workers, we gathered data from 27 449 participants in the WTC Screening, Monitoring, and Treatment Program. The study population included police officers, firefighters, construction workers, and municipal workers. We used the Kaplan-Meier procedure to estimate cumulative and annual incidence of physical disorders (asthma, sinusitis, and gastro-oesophageal reflux disease), mental health disorders (depression, post-traumatic stress disorder [PTSD], and panic disorder), and spirometric abnormalities. Incidence rates were assessed also by level of exposure (days worked at the WTC site and exposure to the dust cloud). Findings 9-year cumulative incidence of asthma was 27.6% (number at risk: 7027), sinusitis 42.3% (5870), and gastro-oesophageal reflux disease 39.3% (5650). In police officers, cumulative incidence of depression was 7.0% (number at risk: 3648), PTSD 9.3% (3761), and panic disorder 8.4% (3780). In other rescue and recovery workers, cumulative incidence of depression was 27.5% (number at risk: 4200), PTSD 31.9% (4342), and panic disorder 21.2% (4953). 9-year cumulative incidence for spirometric abnormalities was 41.8% (number at risk: 5769); three-quarters of these abnormalities were low forced vital capacity. Incidence of most disorders was highest in workers with greatest WTC exposure. Extensive comorbidity was reported within and between physical and mental health disorders. Interpretation 9 years after the 9/11 WTC attacks, rescue and recovery workers continue to have a substantial burden of physical and mental health problems. These findings emphasise the need for continued monitoring and treatment of the WTC rescue and recovery population.. posttraumatic stress symptoms| center disaster| lung-function| health| firefighters| asthma| strategies| exposure| collapse| attacks.	SEP 3-2011	posttraumatic stress symptoms| center disaster| lung-function| health| firefighters| asthma| strategies| exposure| collapse| attacks	Wisnivesky, JP; Teitelbaum, SL; Todd, AC; Boffetta, P; Crane, M; Crowley, L; de la Hoz, RE; Dellenbaugh, C; Harrison, D; Herbert, R; Kim, H; Jeon, Y; Kaplan, J; Katz, C; Levin, S; Luft, B; Markowitz, S; Moline, JM; Ozbay, F; Pietrzak, RH; Shapiro, M; Sharma, V; Skloot, G; Southwick, S; Stevenson, LA; Udasin, I; Wallenstein, S; Landrigan, PJ	Persistence of multiple illnesses in World Trade Center rescue and recovery workers: a cohort study		LANCET		POSTTRAUMATIC STRESS SYMPTOMS; CENTER DISASTER; LUNG-FUNCTION; HEALTH; FIREFIGHTERS; ASTHMA; STRATEGIES; EXPOSURE; COLLAPSE; ATTACKS	Background More than 50000 people participated in the rescue and recovery work that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC). Multiple health problems in these workers were reported in the early years after the disaster. We report incidence and prevalence rates of physical and mental health disorders during the 9 years since the attacks, examine their associations with occupational exposures, and quantify physical and mental health comorbidities. Methods In this longitudinal study of a large cohort of WTC rescue and recovery workers, we gathered data from 27 449 participants in the WTC Screening, Monitoring, and Treatment Program. The study population included police officers, firefighters, construction workers, and municipal workers. We used the Kaplan-Meier procedure to estimate cumulative and annual incidence of physical disorders (asthma, sinusitis, and gastro-oesophageal reflux disease), mental health disorders (depression, post-traumatic stress disorder [PTSD], and panic disorder), and spirometric abnormalities. Incidence rates were assessed also by level of exposure (days worked at the WTC site and exposure to the dust cloud). Findings 9-year cumulative incidence of asthma was 27.6% (number at risk: 7027), sinusitis 42.3% (5870), and gastro-oesophageal reflux disease 39.3% (5650). In police officers, cumulative incidence of depression was 7.0% (number at risk: 3648), PTSD 9.3% (3761), and panic disorder 8.4% (3780). In other rescue and recovery workers, cumulative incidence of depression was 27.5% (number at risk: 4200), PTSD 31.9% (4342), and panic disorder 21.2% (4953). 9-year cumulative incidence for spirometric abnormalities was 41.8% (number at risk: 5769); three-quarters of these abnormalities were low forced vital capacity. Incidence of most disorders was highest in workers with greatest WTC exposure. Extensive comorbidity was reported within and between physical and mental health disorders. Interpretation 9 years after the 9/11 WTC attacks, rescue and recovery workers continue to have a substantial burden of physical and mental health problems. These findings emphasise the need for continued monitoring and treatment of the WTC rescue and recovery population.	32	81	2011	10		General & Internal Medicine
The role of thymic stromal lymphopoietin (TSLP) in allergic disorders. The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies, in both humans and mouse models, have implicated TSLP in the development and progression of atopy and atopic diseases. This review will discuss this work and place TSLP in the inflammatory cascade that leads to allergic disease.. respiratory syncytial virus| airway epithelial-cells| igm(+) b-cells| atopic-dermatitis| eosinophilic esophagitis| netherton-syndrome| in-vitro| inflammation| expression| receptor.	DEC-2010	respiratory syncytial virus| airway epithelial-cells| igm(+) b-cells| atopic-dermatitis| eosinophilic esophagitis| netherton-syndrome| in-vitro| inflammation| expression| receptor	Ziegler, SF	The role of thymic stromal lymphopoietin (TSLP) in allergic disorders		CURRENT OPINION IN IMMUNOLOGY		RESPIRATORY SYNCYTIAL VIRUS; AIRWAY EPITHELIAL-CELLS; IGM(+) B-CELLS; ATOPIC-DERMATITIS; EOSINOPHILIC ESOPHAGITIS; NETHERTON-SYNDROME; IN-VITRO; INFLAMMATION; EXPRESSION; RECEPTOR	The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies, in both humans and mouse models, have implicated TSLP in the development and progression of atopy and atopic diseases. This review will discuss this work and place TSLP in the inflammatory cascade that leads to allergic disease.	55	81	2010	5	10.1016/j.coi.2010.10.020	Immunology
T Cell/Transmembrane, Ig, and Mucin-3 Allelic Variants Differentially Recognize Phosphatidylserine and Mediate Phagocytosis of Apoptotic Cells. T cell/transmembrane, Ig, and mucin (TIM) proteins, identified using a congenic mouse model of asthma, critically regulate innate and adaptive immunity. TIM-1 and TIM-4 are receptors for phosphatidylserine (PtdSer), exposed on the surfaces of apoptotic cells. Herein, we show with structural and biological studies that TIM-3 is also a receptor for PtdSer that binds in a pocket on the N-terminal IgV domain in coordination with a calcium ion. The TIM-3/PtdSer structure is similar to that of TIM-4/PtdSer, reflecting a conserved PtdSer binding mode by TIM family members. Fibroblastic cells expressing mouse or human TIM-3 bound and phagocytosed apoptotic cells, with the BALB/c allelic variant of mouse TIM-3 showing a higher capacity than the congenic C.D2 Es-Hba-allelic variant. These functional differences were due to structural differences in the BC loop of the IgV domain of the TIM-3 polymorphic variants. In contrast to fibroblastic cells, T or B cells expressing TIM-3 formed conjugates with but failed to engulf apoptotic cells. Together these findings indicate that TIM-3-expressing cells can respond to apoptotic cells, but the consequence of TIM-3 engagement of PtdSer depends on the polymorphic variants of and type of cell expressing TIM-3. These findings establish a new paradigm for TIM proteins as PtdSer receptors and unify the function of the TIM gene family, which has been associated with asthma and autoimmunity and shown to modulate peripheral tolerance. The Journal of Immunology, 2010,184: 1918-1930.. tim gene family| immune-responses| in-vivo| peripheral tolerance| airway inflammation| autoimmune-disease| activation| receptor| mechanisms| exposure.	FEB 15-2010	tim gene family| immune-responses| in-vivo| peripheral tolerance| airway inflammation| autoimmune-disease| activation| receptor| mechanisms| exposure	DeKruyff, RH; Bu, X; Ballesteros, A; Santiago, C; Chim, YLE; Lee, HH; Karisola, P; Pichavant, M; Kaplan, GG; Umetsu, DT; Freeman, GJ; Casasnovas, JM	T Cell/Transmembrane, Ig, and Mucin-3 Allelic Variants Differentially Recognize Phosphatidylserine and Mediate Phagocytosis of Apoptotic Cells		JOURNAL OF IMMUNOLOGY		TIM GENE FAMILY; IMMUNE-RESPONSES; IN-VIVO; PERIPHERAL TOLERANCE; AIRWAY INFLAMMATION; AUTOIMMUNE-DISEASE; ACTIVATION; RECEPTOR; MECHANISMS; EXPOSURE	T cell/transmembrane, Ig, and mucin (TIM) proteins, identified using a congenic mouse model of asthma, critically regulate innate and adaptive immunity. TIM-1 and TIM-4 are receptors for phosphatidylserine (PtdSer), exposed on the surfaces of apoptotic cells. Herein, we show with structural and biological studies that TIM-3 is also a receptor for PtdSer that binds in a pocket on the N-terminal IgV domain in coordination with a calcium ion. The TIM-3/PtdSer structure is similar to that of TIM-4/PtdSer, reflecting a conserved PtdSer binding mode by TIM family members. Fibroblastic cells expressing mouse or human TIM-3 bound and phagocytosed apoptotic cells, with the BALB/c allelic variant of mouse TIM-3 showing a higher capacity than the congenic C.D2 Es-Hba-allelic variant. These functional differences were due to structural differences in the BC loop of the IgV domain of the TIM-3 polymorphic variants. In contrast to fibroblastic cells, T or B cells expressing TIM-3 formed conjugates with but failed to engulf apoptotic cells. Together these findings indicate that TIM-3-expressing cells can respond to apoptotic cells, but the consequence of TIM-3 engagement of PtdSer depends on the polymorphic variants of and type of cell expressing TIM-3. These findings establish a new paradigm for TIM proteins as PtdSer receptors and unify the function of the TIM gene family, which has been associated with asthma and autoimmunity and shown to modulate peripheral tolerance. The Journal of Immunology, 2010,184: 1918-1930.	46	81	2010	13	10.4049/jimmunol.0903059	Immunology
Effects of multi-walled carbon nanotubes on a murine allergic airway inflammation model. The development of nanotechnology has increased the risk of exposure to types of particles other than combustion-derived particles in the environment, namely, industrial nanomaterials. On the other hand, patients with bronchial asthma are sensitive to inhaled substances including particulate matters. This Study examined the effects of pulmonary exposure to a type of nano-sized carbon nanotube (multi-walled nanotubes: MWCNT) on allergic airway inflammation in vivo and their cellular mechanisms in vitro. In vivo, ICR mice were divided into 4 experimental groups. Vehicle, MWCNT (50 mu g/animal), ovalbumin (OVA), and OVA + MWCNT were repeatedly administered intratracheally. Bronchoalveolar lavage (BAL) cellularity, lung histology, levels of cytokines related to allergic inflammation in lung homogenates/BAL fluids (BALF's), and serum immunoglobulin levels were Studied. Also, we evaluated the impact of MWCNT (0.1-1 mu g/ml) on the phenotype and function of bone marrow-derived dendritic cells (DC) in vitro. MWCNT aggravated allergen-induced airway inflammation characterized by the infiltration of eosinophils, neutrophils, and mononuclear cells in the lung, and an increase in the number of goblet cells in the bronchial epithelium. MWCNT with allergen amplified lung protein levels of Th cytokines and chemokines compared with allergen alone. MWCNT exhibited adjuvant activity for allergen-specific IgG(1) and IgE. MWCNT significantly increased allergen (OVA)-specific syngeneic T-cell proliferation, particularly at a lower concentration in vitro. Taken together, MWCNT can exacerbate murine allergic airway inflammation, at least partly, via the promotion of a Th-dominant milieu. In addition, the exacerbation may be partly through the inappropriate activation of antigen-presenting cells including DC. (C) 2009 Elsevier Inc. All rights reserved.. multi-walled carbon nanotubes| allergic airway inflammation| antigen-presenting cells| dendritic cells| th immunity|diesel exhaust particles| antigen-presenting cells| mouse bone-marrow| dendritic cells| lung inflammation| intratracheal instillation| bacterial-endotoxin| cytokine expression| particulate matter| pulmonary toxicity.	JUN 15-2009	multi-walled carbon nanotubes| allergic airway inflammation| antigen-presenting cells| dendritic cells| th immunity|diesel exhaust particles| antigen-presenting cells| mouse bone-marrow| dendritic cells| lung inflammation| intratracheal instillation| bacterial-endotoxin| cytokine expression| particulate matter| pulmonary toxicity	Inoue, K; Koike, E; Yanagisaw, R; Hirano, S; Nishikawa, M; Takano, H	Effects of multi-walled carbon nanotubes on a murine allergic airway inflammation model		TOXICOLOGY AND APPLIED PHARMACOLOGY	Multi-walled carbon nanotubes; Allergic airway inflammation; Antigen-presenting cells; Dendritic cells; Th immunity	DIESEL EXHAUST PARTICLES; ANTIGEN-PRESENTING CELLS; MOUSE BONE-MARROW; DENDRITIC CELLS; LUNG INFLAMMATION; INTRATRACHEAL INSTILLATION; BACTERIAL-ENDOTOXIN; CYTOKINE EXPRESSION; PARTICULATE MATTER; PULMONARY TOXICITY	The development of nanotechnology has increased the risk of exposure to types of particles other than combustion-derived particles in the environment, namely, industrial nanomaterials. On the other hand, patients with bronchial asthma are sensitive to inhaled substances including particulate matters. This Study examined the effects of pulmonary exposure to a type of nano-sized carbon nanotube (multi-walled nanotubes: MWCNT) on allergic airway inflammation in vivo and their cellular mechanisms in vitro. In vivo, ICR mice were divided into 4 experimental groups. Vehicle, MWCNT (50 mu g/animal), ovalbumin (OVA), and OVA + MWCNT were repeatedly administered intratracheally. Bronchoalveolar lavage (BAL) cellularity, lung histology, levels of cytokines related to allergic inflammation in lung homogenates/BAL fluids (BALF's), and serum immunoglobulin levels were Studied. Also, we evaluated the impact of MWCNT (0.1-1 mu g/ml) on the phenotype and function of bone marrow-derived dendritic cells (DC) in vitro. MWCNT aggravated allergen-induced airway inflammation characterized by the infiltration of eosinophils, neutrophils, and mononuclear cells in the lung, and an increase in the number of goblet cells in the bronchial epithelium. MWCNT with allergen amplified lung protein levels of Th cytokines and chemokines compared with allergen alone. MWCNT exhibited adjuvant activity for allergen-specific IgG(1) and IgE. MWCNT significantly increased allergen (OVA)-specific syngeneic T-cell proliferation, particularly at a lower concentration in vitro. Taken together, MWCNT can exacerbate murine allergic airway inflammation, at least partly, via the promotion of a Th-dominant milieu. In addition, the exacerbation may be partly through the inappropriate activation of antigen-presenting cells including DC. (C) 2009 Elsevier Inc. All rights reserved.	62	81	2009	11	10.1016/j.taap.2009.04.003	Pharmacology & Pharmacy; Toxicology
CD14 and Toll-like Receptor Gene Polymorphisms, Country Living, and Asthma in Adults. Rationale It has been shown that country living protects against asthma, which may be explained by microbial exposures. Objectives: To study whether single nucleotide polymorphisms (SNPs) in CD 14 and Toll-like receptor (TLR) 2, TLR4 and TLR9 genes are associated with asthma in adults, and whether these SNPs modify associations between country living and asthma. Methods: Twenty-five SNPs in CD14, TLR2, TLR4, and TLR9 genes were genotyped in adult subjects from the French Epidemiological study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). We conducted a case-control analysis on unrelated subjects (239 with asthma and 596 without asthma), and a family-based association test (FBAT) in 192 families ascertained through probands with asthma. Measurements and Main Results: The TLR2/+596 C allele was associated with an increased risk for asthma in both case-control and family-based analyses (under a dominant model, odds ratio [OR] 1.91 and 95% confidence interval [CI] 1.34-2.72, P = 0.0003; Z statistics from FBAT = 2.48, P = 0.01). In skin prick test (SPT) positive subjects, the CD14/-260 C allele was negatively associated with asthma (additive model, OR 0.66; CI 0.48-0.91). Significant gene-environment interactions between variation in CD14 and TLR genes and country living during childhood were found for ten SNPs. In SPT positive subjects carrying CD14/-260 CC, country living protected against asthma (OR, 0.32; 95% CI, 0.12-0.85), whereas country living was not associated with asthma in subjects who were atopic and carrying CD14/-260 T (OR, 1.11; 95% CI, 0.65-1.90) (gene-environment interaction, P < 0.05). Conclusions: TLR2 and CD14 SNPs were associated with asthma and atopic asthma respectively. In addition, CD14, TLR2, TLR4, and TLR9 SNPs modified associations between country living and asthma.. asthma| atopy| epidemiology| gene-environment interaction| hygiene hypothesis|young danish farmers| bronchial hyperresponsiveness| c-159t polymorphism| endotoxin exposure| immunoglobulin-e| atopy| association| environment| children| egea.	MAR 1-2009	asthma| atopy| epidemiology| gene-environment interaction| hygiene hypothesis|young danish farmers| bronchial hyperresponsiveness| c-159t polymorphism| endotoxin exposure| immunoglobulin-e| atopy| association| environment| children| egea	Smit, LAM; Siroux, V; Bouzigon, E; Oryszczyn, MP; Lathrop, M; Demenais, F; Kauffmann, F	CD14 and Toll-like Receptor Gene Polymorphisms, Country Living, and Asthma in Adults		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; atopy; epidemiology; gene-environment interaction; hygiene hypothesis	YOUNG DANISH FARMERS; BRONCHIAL HYPERRESPONSIVENESS; C-159T POLYMORPHISM; ENDOTOXIN EXPOSURE; IMMUNOGLOBULIN-E; ATOPY; ASSOCIATION; ENVIRONMENT; CHILDREN; EGEA	Rationale It has been shown that country living protects against asthma, which may be explained by microbial exposures. Objectives: To study whether single nucleotide polymorphisms (SNPs) in CD 14 and Toll-like receptor (TLR) 2, TLR4 and TLR9 genes are associated with asthma in adults, and whether these SNPs modify associations between country living and asthma. Methods: Twenty-five SNPs in CD14, TLR2, TLR4, and TLR9 genes were genotyped in adult subjects from the French Epidemiological study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). We conducted a case-control analysis on unrelated subjects (239 with asthma and 596 without asthma), and a family-based association test (FBAT) in 192 families ascertained through probands with asthma. Measurements and Main Results: The TLR2/+596 C allele was associated with an increased risk for asthma in both case-control and family-based analyses (under a dominant model, odds ratio [OR] 1.91 and 95% confidence interval [CI] 1.34-2.72, P = 0.0003; Z statistics from FBAT = 2.48, P = 0.01). In skin prick test (SPT) positive subjects, the CD14/-260 C allele was negatively associated with asthma (additive model, OR 0.66; CI 0.48-0.91). Significant gene-environment interactions between variation in CD14 and TLR genes and country living during childhood were found for ten SNPs. In SPT positive subjects carrying CD14/-260 CC, country living protected against asthma (OR, 0.32; 95% CI, 0.12-0.85), whereas country living was not associated with asthma in subjects who were atopic and carrying CD14/-260 T (OR, 1.11; 95% CI, 0.65-1.90) (gene-environment interaction, P < 0.05). Conclusions: TLR2 and CD14 SNPs were associated with asthma and atopic asthma respectively. In addition, CD14, TLR2, TLR4, and TLR9 SNPs modified associations between country living and asthma.	42	81	2009	6	10.1164/rccm.200810-1533OC	General & Internal Medicine; Respiratory System
The danger within: endogenous danger signals, atopy and asthma. In allergic asthmatics, airway inflammation is triggered by specific (inhalation of allergen such as house dust mite allergen and pollen spores) or non-specific triggers (such as air pollutants and viral infection). Most of these inhaled particles are immunologically inert. Dendritic cells (DCs) are essential for priming and T helper-2 differentiation of naive T cells towards aeroallergens. Contamination of antigens with pattern-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS), is required to activate DCs to mount an immune response. Damage-associated molecular patterns (DAMPs), such as uric acid and adenosine triphosphate (ATP), also contribute to the induction of inflammation by activation and recruitment of various inflammatory cells. Compelling evidence suggests that a tight collaboration between PAMPs and DAMPs is needed to start an immune response to allergens. Several studies have recently demonstrated an important role of endogenous danger signals at the inception and maintenance phase of allergic disease. Further research into this area should focus on the possible role of these factors in maintenance of chronic disease and induction of airway remodelling.. toll-like receptors| regulatory t-cells| eosinophilic airway inflammation| nod-like receptors| dendritic cells| inhaled antigen| nonatopic asthma| th2 responses| p2x receptors| mouse model.	JAN-2009	toll-like receptors| regulatory t-cells| eosinophilic airway inflammation| nod-like receptors| dendritic cells| inhaled antigen| nonatopic asthma| th2 responses| p2x receptors| mouse model	Willart, MAM; Lambrecht, BN	The danger within: endogenous danger signals, atopy and asthma		CLINICAL AND EXPERIMENTAL ALLERGY		TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; EOSINOPHILIC AIRWAY INFLAMMATION; NOD-LIKE RECEPTORS; DENDRITIC CELLS; INHALED ANTIGEN; NONATOPIC ASTHMA; TH2 RESPONSES; P2X RECEPTORS; MOUSE MODEL	In allergic asthmatics, airway inflammation is triggered by specific (inhalation of allergen such as house dust mite allergen and pollen spores) or non-specific triggers (such as air pollutants and viral infection). Most of these inhaled particles are immunologically inert. Dendritic cells (DCs) are essential for priming and T helper-2 differentiation of naive T cells towards aeroallergens. Contamination of antigens with pattern-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS), is required to activate DCs to mount an immune response. Damage-associated molecular patterns (DAMPs), such as uric acid and adenosine triphosphate (ATP), also contribute to the induction of inflammation by activation and recruitment of various inflammatory cells. Compelling evidence suggests that a tight collaboration between PAMPs and DAMPs is needed to start an immune response to allergens. Several studies have recently demonstrated an important role of endogenous danger signals at the inception and maintenance phase of allergic disease. Further research into this area should focus on the possible role of these factors in maintenance of chronic disease and induction of airway remodelling.	82	81	2009	8	10.1111/j.1365-2222.2008.03118.x	Allergy; Immunology
"The healthy worker effect in asthma - Work may cause asthma, but asthma may also influence work. Despite the increasing attention to the relationship between asthma and work exposures, occupational asthma remains underrecognized and its population burden underestimated. This may be due, in part, to the fact that traditional approaches to studying asthma in populations cannot adequately take into account the healthy worker effect (HWE). The HWE is the potential bias caused by the phenomenon that sicker individuals may choose work environments in which exposures are low, they may be excluded from being hired; or once hired, they may seek transfer to less exposed jobs or leave work. This article demonstrates that population- and workplace-based asthma studies are particularly subject to HWE bias, which leads to underestimates of relative risks. Our objective is to describe the HWE as it relates to asthma research, and to discuss the significance of taking HWE bias into account in designing and interpreting asthma studies. We also discuss the importance of understanding HWE bias for public health practitioners and for clinicians. Finally, we emphasize the timeliness of this review in light of the many longitudinal ""child to young adult"" asthma cohort studies currently underway. These prospective studies will soon provide an ideal opportunity to examine the impact of early workplace environments on asthma in young adults. We urge occupational and childhood asthma epidemiologists collaborate to ensure that this opportunity is not lost.. epidemiology| asthma| occupational exposure| healthy worker effect|marginal structural models| body shop workers| respiratory symptoms| occupational epidemiology| airway responsiveness| metalworking fluids| united-states| follow-up| selection| population."	JAN 1-2008	epidemiology| asthma| occupational exposure| healthy worker effect|marginal structural models| body shop workers| respiratory symptoms| occupational epidemiology| airway responsiveness| metalworking fluids| united-states| follow-up| selection| population	Le Moual, N; Kauffmann, F; Eisen, EA; Kennedy, SM	The healthy worker effect in asthma - Work may cause asthma, but asthma may also influence work		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	epidemiology; asthma; occupational exposure; healthy worker effect	MARGINAL STRUCTURAL MODELS; BODY SHOP WORKERS; RESPIRATORY SYMPTOMS; OCCUPATIONAL EPIDEMIOLOGY; AIRWAY RESPONSIVENESS; METALWORKING FLUIDS; UNITED-STATES; FOLLOW-UP; SELECTION; POPULATION	"Despite the increasing attention to the relationship between asthma and work exposures, occupational asthma remains underrecognized and its population burden underestimated. This may be due, in part, to the fact that traditional approaches to studying asthma in populations cannot adequately take into account the healthy worker effect (HWE). The HWE is the potential bias caused by the phenomenon that sicker individuals may choose work environments in which exposures are low, they may be excluded from being hired; or once hired, they may seek transfer to less exposed jobs or leave work. This article demonstrates that population- and workplace-based asthma studies are particularly subject to HWE bias, which leads to underestimates of relative risks. Our objective is to describe the HWE as it relates to asthma research, and to discuss the significance of taking HWE bias into account in designing and interpreting asthma studies. We also discuss the importance of understanding HWE bias for public health practitioners and for clinicians. Finally, we emphasize the timeliness of this review in light of the many longitudinal ""child to young adult"" asthma cohort studies currently underway. These prospective studies will soon provide an ideal opportunity to examine the impact of early workplace environments on asthma in young adults. We urge occupational and childhood asthma epidemiologists collaborate to ensure that this opportunity is not lost."	53	81	2008	7	10.1164/rccm.200703-415PP	General & Internal Medicine; Respiratory System
Selective inducible nitric oxide synthase inhibition has no effect on allergen challenge in asthma. Rationale Exhaled breath nitric oxide (F-ENO) is increased in asthma. NO is produced predominantly by inducible nitric oxide synthase (NOS). Objectives: We evaluated the selective and potent NOS inhibitor GW274150 in asthma. Methods: Twenty-eight steroid-naive patients with asthma participated in a double-blind, randomized, double-dummy, placebo-controlled, three-period cross-over study. Subjects received GW274150 (90 mg), montelukast (10 mg), or placebo once daily for 14 days. FENO was assessed predose on Days 1, 7, 10, and 14. Adenosine 5 '-monophosphate (AMP) challenge was performed on Day 10, allergen challenge on Day 14 followed by methacholine challenge (MCh) 24 hours later, and then bronchoscopy. Measurements and Main Results: GW274150 reduced predose FENO by 73, 75, and 71% on Days 7, 10, and 14, respectively, compared with placebo. Montelukast did not reduce FENO. GW274150 did not inhibit AMP reactivity whereas for montelukast there was a trend toward inhibition: the mean doubling dose difference versus placebo was 0.64 (95% confidence interval [95% Cl], 0 to 1.28). GW274150 did not inhibit early (EAR) and late (LAR) asthmatic responses to allergen, or MCh reactivity, despite reduced FEND levels. Montelukast inhibited EAR and LAIR FEV1; the mean difference versus placebo for minimal FEV1 was 0.37 L (95% Cl, 0.19 to 0.55) and 0.18 L (95% Cl, 0.04 to 0.32), respectively. MCh reactivity was inhibited by montelukast (mean doubling dose difference vs. placebo, 0.51; 95% Cl, 0.02 to 1.01). GW271540 also had no effect on inflammatory cell numbers in bronchoalveolar lavage fluid after allergen challenge. Conclusions: Selective iNOS inhibition effectively reduces FENO but does not affect airway hyperreactivity or airway inflammatory cell numbers after allergen challenge in subjects with asthma.. nitric oxide| bronchial hyperreactivity|reactive nitrogen| airway responsiveness| exhaled air| mild asthma| respiratory-tract| in-vitro| inflammation| gw274150| montelukast| potent.	NOV 15-2007	nitric oxide| bronchial hyperreactivity|reactive nitrogen| airway responsiveness| exhaled air| mild asthma| respiratory-tract| in-vitro| inflammation| gw274150| montelukast| potent	Singh, D; Richards, D; Knowles, RG; Schwartz, S; Woodcock, A; Langley, S; O'Connor, BJ	Selective inducible nitric oxide synthase inhibition has no effect on allergen challenge in asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	nitric oxide; bronchial hyperreactivity	REACTIVE NITROGEN; AIRWAY RESPONSIVENESS; EXHALED AIR; MILD ASTHMA; RESPIRATORY-TRACT; IN-VITRO; INFLAMMATION; GW274150; MONTELUKAST; POTENT	Rationale Exhaled breath nitric oxide (F-ENO) is increased in asthma. NO is produced predominantly by inducible nitric oxide synthase (NOS). Objectives: We evaluated the selective and potent NOS inhibitor GW274150 in asthma. Methods: Twenty-eight steroid-naive patients with asthma participated in a double-blind, randomized, double-dummy, placebo-controlled, three-period cross-over study. Subjects received GW274150 (90 mg), montelukast (10 mg), or placebo once daily for 14 days. FENO was assessed predose on Days 1, 7, 10, and 14. Adenosine 5 '-monophosphate (AMP) challenge was performed on Day 10, allergen challenge on Day 14 followed by methacholine challenge (MCh) 24 hours later, and then bronchoscopy. Measurements and Main Results: GW274150 reduced predose FENO by 73, 75, and 71% on Days 7, 10, and 14, respectively, compared with placebo. Montelukast did not reduce FENO. GW274150 did not inhibit AMP reactivity whereas for montelukast there was a trend toward inhibition: the mean doubling dose difference versus placebo was 0.64 (95% confidence interval [95% Cl], 0 to 1.28). GW274150 did not inhibit early (EAR) and late (LAR) asthmatic responses to allergen, or MCh reactivity, despite reduced FEND levels. Montelukast inhibited EAR and LAIR FEV1; the mean difference versus placebo for minimal FEV1 was 0.37 L (95% Cl, 0.19 to 0.55) and 0.18 L (95% Cl, 0.04 to 0.32), respectively. MCh reactivity was inhibited by montelukast (mean doubling dose difference vs. placebo, 0.51; 95% Cl, 0.02 to 1.01). GW271540 also had no effect on inflammatory cell numbers in bronchoalveolar lavage fluid after allergen challenge. Conclusions: Selective iNOS inhibition effectively reduces FENO but does not affect airway hyperreactivity or airway inflammatory cell numbers after allergen challenge in subjects with asthma.	44	81	2007	6	10.1164/rccm.200704-588OC	General & Internal Medicine; Respiratory System
TIM-4 expressed by mucosal dendritic cells plays a critical role in food antigen-specific Th2 differentiation and intestinal allergy. Background & Aims: Food allergy accounts for Significant morbidity. The etiology and immune mechanisms of food allergy, however, have remained poorly understood. In this study, we aimed to determine the role of T-cell immunoglobulin-domain and mucin-domain (TIM)-4, a recently identified member of cell surface molecules, in the pathogenesis of intestinal allergy in a murine model. Methods: We report that TIM-4 as well as costimulatory molecules were up-regulated in intestinal mucosal dendritic cells by in vitro or in vivo exposure to Staphylococcus enterotoxin B (SEB). SEB-conditioned intestinal dendritic cells loaded with a food macromolecule ovalbumin (OVA) induced potent OVA-specific T-helper (Th)2 lymphocyte responses in vitro and such Th2 responses were inhibited completely by TIM-4 blockade. Results: In vivo exposure to both SEB and OVA resulted in OVA-specific Th2 differentiation and intestinal allergic responses including increased serum immunoglobulin E and Th2 cytokine levels, activation of OVA-specific Th2 cells detected both ex vivo and in situ, and mast cell degranulation. Of importance, in vivo abrogation of TIM-4 or its cognate ligand TIM-1 by using a polyclonal antibody remarkably dampened Th2 differentiation and intestinal allergy. Conclusions: Our study thus identifies TIM-4 as a novel molecule critically required for the development of intestinal allergy.. murine model| mouse model| t-cells| transport| proteins| mice| ige| sensitization| antibodies| tolerance.	NOV-2007	murine model| mouse model| t-cells| transport| proteins| mice| ige| sensitization| antibodies| tolerance	Yang, PC; Xing, Z; Berin, CM; Soderholm, JD; Feng, BS; Wu, L; Yeh, C	TIM-4 expressed by mucosal dendritic cells plays a critical role in food antigen-specific Th2 differentiation and intestinal allergy		GASTROENTEROLOGY		MURINE MODEL; MOUSE MODEL; T-CELLS; TRANSPORT; PROTEINS; MICE; IGE; SENSITIZATION; ANTIBODIES; TOLERANCE	Background & Aims: Food allergy accounts for Significant morbidity. The etiology and immune mechanisms of food allergy, however, have remained poorly understood. In this study, we aimed to determine the role of T-cell immunoglobulin-domain and mucin-domain (TIM)-4, a recently identified member of cell surface molecules, in the pathogenesis of intestinal allergy in a murine model. Methods: We report that TIM-4 as well as costimulatory molecules were up-regulated in intestinal mucosal dendritic cells by in vitro or in vivo exposure to Staphylococcus enterotoxin B (SEB). SEB-conditioned intestinal dendritic cells loaded with a food macromolecule ovalbumin (OVA) induced potent OVA-specific T-helper (Th)2 lymphocyte responses in vitro and such Th2 responses were inhibited completely by TIM-4 blockade. Results: In vivo exposure to both SEB and OVA resulted in OVA-specific Th2 differentiation and intestinal allergic responses including increased serum immunoglobulin E and Th2 cytokine levels, activation of OVA-specific Th2 cells detected both ex vivo and in situ, and mast cell degranulation. Of importance, in vivo abrogation of TIM-4 or its cognate ligand TIM-1 by using a polyclonal antibody remarkably dampened Th2 differentiation and intestinal allergy. Conclusions: Our study thus identifies TIM-4 as a novel molecule critically required for the development of intestinal allergy.	24	81	2007	12	10.1053/j.gastro.2007.08.006	Gastroenterology & Hepatology
Proteases as Th2 adjuvants. Several cysteine and serine protease allergens have been cloned from house dust mites, including Der p 1, Der p 3, Der p 6, and Der p 9. A significant body of evidence suggests that these allergens mimic helper T (Th) 2 cell adjuvants. Der p 1 cleaves CD23 from activated B cells and CD25 from T cells. Der p I proteolytically degrades tight junctions in lung epithelium and causes release of proinflammatory cytokines from bronchial epithelial cells, mast cells, and basophils. These synergistic effects of mite enzyme allergens may promote IgE synthesis and have direct inflammatory effects on lung epithelium, which could explain why mite allergens are associated with asthma. The crystal structures of the proenzyme and mature forms of Der p 1 have been determined, as have the structures of other indoor allergens that are not enzymes (eg, Der p 2, Fel d 1, and Bla g 2). Cockroach allergens are strongly associated with asthma in US inner cities, yet none of the cockroach allergens that have been cloned are proteolytic enzymes. Thus although mite proteases allergens may act as Th2 adjuvants, a paradoxical effect is that other allergens may elicit strong Th2 responses in the absence of enzyme activity.. house-dust mite| cockroach allergen bla-g-2| dermatophagoides-pteronyssinus| crystal-structure| epithelial-cells| serine-protease| molecular characterization| recombinant pro-der-p-1| proteolytic activity| antibody-response.	SEP-2007	house-dust mite| cockroach allergen bla-g-2| dermatophagoides-pteronyssinus| crystal-structure| epithelial-cells| serine-protease| molecular characterization| recombinant pro-der-p-1| proteolytic activity| antibody-response	Chapman, MD; Wunschmann, S; Pomes, A	Proteases as Th2 adjuvants		CURRENT ALLERGY AND ASTHMA REPORTS		HOUSE-DUST MITE; COCKROACH ALLERGEN BLA-G-2; DERMATOPHAGOIDES-PTERONYSSINUS; CRYSTAL-STRUCTURE; EPITHELIAL-CELLS; SERINE-PROTEASE; MOLECULAR CHARACTERIZATION; RECOMBINANT PRO-DER-P-1; PROTEOLYTIC ACTIVITY; ANTIBODY-RESPONSE	Several cysteine and serine protease allergens have been cloned from house dust mites, including Der p 1, Der p 3, Der p 6, and Der p 9. A significant body of evidence suggests that these allergens mimic helper T (Th) 2 cell adjuvants. Der p 1 cleaves CD23 from activated B cells and CD25 from T cells. Der p I proteolytically degrades tight junctions in lung epithelium and causes release of proinflammatory cytokines from bronchial epithelial cells, mast cells, and basophils. These synergistic effects of mite enzyme allergens may promote IgE synthesis and have direct inflammatory effects on lung epithelium, which could explain why mite allergens are associated with asthma. The crystal structures of the proenzyme and mature forms of Der p 1 have been determined, as have the structures of other indoor allergens that are not enzymes (eg, Der p 2, Fel d 1, and Bla g 2). Cockroach allergens are strongly associated with asthma in US inner cities, yet none of the cockroach allergens that have been cloned are proteolytic enzymes. Thus although mite proteases allergens may act as Th2 adjuvants, a paradoxical effect is that other allergens may elicit strong Th2 responses in the absence of enzyme activity.	41	81	2007	5	10.1007/s11882-007-0055-6	Allergy; Immunology
Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort. Background: The timing of allergen sensitization is controversial, with conflicting evidence suggesting transplacental priming versus exclusively postnatal priming. Resolution of this question is important in relation to rational design of allergy prevention strategies, particularly the issue of allergen avoidance during pregnancy. Objective: To elucidate the kinetics of sensitization in high-risk children during their first 2 years of life. Methods: We prospectively studied house dust mite (HDM)specific IgE and IgG(4) antibody production and associated T-cell immunity in a cohort of 200 high-risk infants. Parallel antibody studies tracked responses against a broader panel of inhalant and dietary allergens including peanut. Results: HDM-induced T-H(2) responses in PBMC from 6 months onward, particularly IL-4 and IL-5, correlated increasingly strongly with sensitization outcomes at 2 years, and a I contrasting negative relationship was observed with IFN-T response capacity. HDM-induced T-cell responses in cord blood, although common, were unrelated to subsequent sensitization. Transient HDM-IgE (and IgG4) production frequently peaked at 6 or 12 months before returning to baseline, which suggests the onset of protective tolerance. This finding contrasted wi th progressively increasing HDM titers in children sensitized by 2 years of age. Comparably contrasting patterns were observed in peanut-specific responses in sensitized versus nonsensitized children. Conclusion: Priming of T-H(2) responses associated with persistent HDM-IgE production occurs entirely postnatally, as HDM reactivity in cord blood seems nonspecific and is unrelated to subsequent development of allergen-specific T-H(2) memory or TgE. Clinical implications: These findings question the scientific basis for existing recommendations for allergen avoidance by high-risk women during pregnancy.. atopy| cytokines| ige| igg(4)| t-cell memory| t(h)2|house-dust mite| t-cell responses| cord-blood| inhalant allergens| indoor allergens| maternal intake| early-childhood| grass-pollen| dietary egg| children.	MAY-2007	atopy| cytokines| ige| igg(4)| t-cell memory| t(h)2|house-dust mite| t-cell responses| cord-blood| inhalant allergens| indoor allergens| maternal intake| early-childhood| grass-pollen| dietary egg| children	Rowe, J; Kusel, M; Holt, BJ; Suriyaarachchi, D; Serralha, M; Hollams, E; Yerkovich, ST; Subrata, LS; Ladyman, C; Sadowska, A; Gillett, J; Fisher, E; Loh, R; Soderstrom, L; Ahistedt, S; Sly, PD; Holt, PG	Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopy; cytokines; IgE; IgG(4); T-cell memory; T(H)2	HOUSE-DUST MITE; T-CELL RESPONSES; CORD-BLOOD; INHALANT ALLERGENS; INDOOR ALLERGENS; MATERNAL INTAKE; EARLY-CHILDHOOD; GRASS-POLLEN; DIETARY EGG; CHILDREN	Background: The timing of allergen sensitization is controversial, with conflicting evidence suggesting transplacental priming versus exclusively postnatal priming. Resolution of this question is important in relation to rational design of allergy prevention strategies, particularly the issue of allergen avoidance during pregnancy. Objective: To elucidate the kinetics of sensitization in high-risk children during their first 2 years of life. Methods: We prospectively studied house dust mite (HDM)specific IgE and IgG(4) antibody production and associated T-cell immunity in a cohort of 200 high-risk infants. Parallel antibody studies tracked responses against a broader panel of inhalant and dietary allergens including peanut. Results: HDM-induced T-H(2) responses in PBMC from 6 months onward, particularly IL-4 and IL-5, correlated increasingly strongly with sensitization outcomes at 2 years, and a I contrasting negative relationship was observed with IFN-T response capacity. HDM-induced T-cell responses in cord blood, although common, were unrelated to subsequent sensitization. Transient HDM-IgE (and IgG4) production frequently peaked at 6 or 12 months before returning to baseline, which suggests the onset of protective tolerance. This finding contrasted wi th progressively increasing HDM titers in children sensitized by 2 years of age. Comparably contrasting patterns were observed in peanut-specific responses in sensitized versus nonsensitized children. Conclusion: Priming of T-H(2) responses associated with persistent HDM-IgE production occurs entirely postnatally, as HDM reactivity in cord blood seems nonspecific and is unrelated to subsequent development of allergen-specific T-H(2) memory or TgE. Clinical implications: These findings question the scientific basis for existing recommendations for allergen avoidance by high-risk women during pregnancy.	49	81	2007	10	10.1016/j.jaci.2007.02.016	Allergy; Immunology
Associations of tumor necrosis factor G-308A with childhood asthma and wheezing. Rationale: Tumor necrosis factor (TNF) mediates a spectrum of airway inflammatory responses, including those to air pollutants, and is an asthma candidate gene. One TNF promoter variant (G-308A) affects expression of TNF and has been associated with inflammatory diseases; however, studies of asthma have been inconsistent. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the -308 TNF polymorphism with asthma may vary by ozone exposure and variants of oxidant defense genes glutathione-S-transferase (GST) M1 and GSTP1. Objectives: To investigate the association of TNF G-308A with asthma and wheezing and to determine whether these associations vary with ozone exposure and GSTM1 and GSTP1 genotype. Methods: We studied associations of TNF-308 genotype with lifetime and current wheezing and asthma among 3,699 children in the Children's Health Study. We examined differences in associations with community ozone and by GSTM1 null and GSTP1 105 Ile/Val (A105G) genotype. Results: Children with TNF-308 GG had decreased risk of asthma (odds ratio, 0.8; 95% confidence interval, 0.7-0.9) and lifetime wheezing (odds ratio, 0.8; 95% confidence interval, 0.7-0.9). The protective effects of GG genotype on wheezing outcomes were of greater magnitude in lower compared with higher ozone communities. These findings were replicated in the two cohorts of fourth-grade children recruited in 1993 and 1996. The reduction of the protective effect from the -308 GG genotype with higher ozone exposure was most marked in the GSTM1 null and GSTP1 Ile/Ile groups. Conclusions: The TNF-308 GG genotype may have a protective role in asthma pathogenesis, depending on airway oxidative stress levels.. child| genetic epidemiology| lung|glutathione-s-transferase| gene-environment interactions| southern california communities| air-pollution| factor-alpha| tnf-alpha| atopic asthma| induced inflammation| allergic responses| differing levels.	MAY 1-2006	child| genetic epidemiology| lung|glutathione-s-transferase| gene-environment interactions| southern california communities| air-pollution| factor-alpha| tnf-alpha| atopic asthma| induced inflammation| allergic responses| differing levels	Li, YF; Gauderman, WJ; Avol, E; Dubeau, L; Gilliland, FD	Associations of tumor necrosis factor G-308A with childhood asthma and wheezing		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	child; genetic epidemiology; lung	GLUTATHIONE-S-TRANSFERASE; GENE-ENVIRONMENT INTERACTIONS; SOUTHERN CALIFORNIA COMMUNITIES; AIR-POLLUTION; FACTOR-ALPHA; TNF-ALPHA; ATOPIC ASTHMA; INDUCED INFLAMMATION; ALLERGIC RESPONSES; DIFFERING LEVELS	Rationale: Tumor necrosis factor (TNF) mediates a spectrum of airway inflammatory responses, including those to air pollutants, and is an asthma candidate gene. One TNF promoter variant (G-308A) affects expression of TNF and has been associated with inflammatory diseases; however, studies of asthma have been inconsistent. Because ozone produces oxidative stress, increased airway TNF, and inflammation, the associations of the -308 TNF polymorphism with asthma may vary by ozone exposure and variants of oxidant defense genes glutathione-S-transferase (GST) M1 and GSTP1. Objectives: To investigate the association of TNF G-308A with asthma and wheezing and to determine whether these associations vary with ozone exposure and GSTM1 and GSTP1 genotype. Methods: We studied associations of TNF-308 genotype with lifetime and current wheezing and asthma among 3,699 children in the Children's Health Study. We examined differences in associations with community ozone and by GSTM1 null and GSTP1 105 Ile/Val (A105G) genotype. Results: Children with TNF-308 GG had decreased risk of asthma (odds ratio, 0.8; 95% confidence interval, 0.7-0.9) and lifetime wheezing (odds ratio, 0.8; 95% confidence interval, 0.7-0.9). The protective effects of GG genotype on wheezing outcomes were of greater magnitude in lower compared with higher ozone communities. These findings were replicated in the two cohorts of fourth-grade children recruited in 1993 and 1996. The reduction of the protective effect from the -308 GG genotype with higher ozone exposure was most marked in the GSTM1 null and GSTP1 Ile/Ile groups. Conclusions: The TNF-308 GG genotype may have a protective role in asthma pathogenesis, depending on airway oxidative stress levels.	60	81	2006	7	10.1164/rccm.200508-1256OC	General & Internal Medicine; Respiratory System
Effects of ultrafine carbon particle inhalation on allergic inflammation of the lung. Background: Epidemiologic studies show that exposure to particulate air pollution is associated with asthma exacerbation. Ultrafine particles (diameter <100 nm) may contribute to these adverse effects. Objective: To investigate potential adjuvant activity of inhaled elemental carbon ultrafine particles (EC-UFPs) on allergic airway inflammation. Methods: The effects of ultrafine particle inhalation on allergic airway inflammation was analyzed in ovalbumin-sensitized mice and nonsensitized controls. Particle exposure (526 mu g/m(3), 24 hours) was performed 24, 96, or 168 hours before or 24 or 72 hours after ovalbumin aerosol challenge. Allergic inflammation was analyzed at different time points after allergen challenge by means of bronchoalveolar lavage cell count and cytokine/total protein assays, lung histology, and airway hyperresponsiveness. Results: In sensitized mice, inhalation of ultrafine particles 24 hours before allergen challenge caused a significant increase of bronchoalveolar lavage inflammatory cell infiltrate, protein, IL-4, IL-5, and IL-13 compared with relevant controls. These adjuvant effects were dose- and time-dependent and were still present when particle exposure was performed 4 days before allergen challenge. The adjuvant effect of ultrafine particles was also documented by increased mucus production, peribronchiolar and perivascular inflammation, and enhanced airway hyperresponsiveness. In contrast, particle exposure in sensitized mice after allergen challenge caused only moderate effects, such as a delay of inflammatory infiltrate and a reduction of cytokines in bronchoalveolar lavage fluid. Conclusion: Exposure to ultrafine carbon particles before allergen challenge exerts strong adjuvant effects on the manifestation of allergic airway inflammation. Allergen-sensitized individuals may therefore be more susceptible to detrimental health effects of ultrafine particles.. particulate matter| elemental carbon ultrafine particles| allergic inflammation|particulate air-pollution| emergency-room visits| diesel exhaust particles| fine particles| in-vivo| respiratory health| adjuvant activity| oxidative stress| asthma| mice.	APR-2006	particulate matter| elemental carbon ultrafine particles| allergic inflammation|particulate air-pollution| emergency-room visits| diesel exhaust particles| fine particles| in-vivo| respiratory health| adjuvant activity| oxidative stress| asthma| mice	Alessandrini, F; Schulz, H; Takenaka, S; Lentner, B; Karg, E; Behrendt, H; Jakob, T	Effects of ultrafine carbon particle inhalation on allergic inflammation of the lung		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	particulate matter; elemental carbon ultrafine particles; allergic inflammation	PARTICULATE AIR-POLLUTION; EMERGENCY-ROOM VISITS; DIESEL EXHAUST PARTICLES; FINE PARTICLES; IN-VIVO; RESPIRATORY HEALTH; ADJUVANT ACTIVITY; OXIDATIVE STRESS; ASTHMA; MICE	Background: Epidemiologic studies show that exposure to particulate air pollution is associated with asthma exacerbation. Ultrafine particles (diameter <100 nm) may contribute to these adverse effects. Objective: To investigate potential adjuvant activity of inhaled elemental carbon ultrafine particles (EC-UFPs) on allergic airway inflammation. Methods: The effects of ultrafine particle inhalation on allergic airway inflammation was analyzed in ovalbumin-sensitized mice and nonsensitized controls. Particle exposure (526 mu g/m(3), 24 hours) was performed 24, 96, or 168 hours before or 24 or 72 hours after ovalbumin aerosol challenge. Allergic inflammation was analyzed at different time points after allergen challenge by means of bronchoalveolar lavage cell count and cytokine/total protein assays, lung histology, and airway hyperresponsiveness. Results: In sensitized mice, inhalation of ultrafine particles 24 hours before allergen challenge caused a significant increase of bronchoalveolar lavage inflammatory cell infiltrate, protein, IL-4, IL-5, and IL-13 compared with relevant controls. These adjuvant effects were dose- and time-dependent and were still present when particle exposure was performed 4 days before allergen challenge. The adjuvant effect of ultrafine particles was also documented by increased mucus production, peribronchiolar and perivascular inflammation, and enhanced airway hyperresponsiveness. In contrast, particle exposure in sensitized mice after allergen challenge caused only moderate effects, such as a delay of inflammatory infiltrate and a reduction of cytokines in bronchoalveolar lavage fluid. Conclusion: Exposure to ultrafine carbon particles before allergen challenge exerts strong adjuvant effects on the manifestation of allergic airway inflammation. Allergen-sensitized individuals may therefore be more susceptible to detrimental health effects of ultrafine particles.	50	81	2006	7	10.1016/j.jaci.2005.11.046	Allergy; Immunology
Personal exposure to airborne dust and microorganisms in agricultural environments. Airborne dust and microorganisms are associated with respiratory diseases and increased mortality, and morbidity. Farmers are at high risk of exposure to both of these hazards. Very limited information, however is available on the combined exposures to both hazards on different types of farms. Moreover most of the previous studies have measured the mass concentration of particles ignoring the particle size. In this study, farmers' exposure to airborne dust and microorganisms was studied using our newly developed personal sampling system. Particle number concentration and size distribution were measured with an optical particle counter Simultaneously, particles were collected on a filter and analyzed for microorganisms. The field measurements were conducted in animal confinements (swine, poultry, and dairy) and during grain harvesting (corn and soybean). The ye concentrations on the results show the following avera workers' breathing zone.- 1. 7 x 10(6) to 2.9 x 10(7) particles/m(3) for total dust, 0.9 x 10(3) to 3.9 x 10(4) spores/m(3) for total fungal spores, 0.3 x 10(3) to 3.6 x 10(4) CFU/m(3) for culturable fungal spores, 0.3 x 10(4) to 3.3 x 10(8) CFU/m(3) for culturable bacteria, and limit of detection (LOD) to 2.8 x 103 CFU/m(3) for culturable actinomycetes in animal confinements. The respective concentrations were 4.4 x 10(6) to 5.8 x 10(7) particles/m(3), 3.4 x 10(4) to 6.1 x 10(6) spores/m(3), 8.2 x 10(4) to 7.4 x 10(6) CFU/m(3), 0.4 x 10(5) to 1.4 x 10(6) CFU/m(3), and LOD to 2.6 x 10(4) CFU/m(3) during grain harvesting. The highest contribution of large particles (3-10 mu m) in total particles was found during grain harvesting, whereas the size distribution was dominated by smaller particles (< 3 mu m) in animal confinements. High fraction (up to 37%) of particles between 2-10 mu m was found to be fungal spores. The results indicate that an increase in the concentration of large dust particles (2-10 mu m) during grain harvesting was partially, attributed to the increase in the concentration of the fungal spores. Overall, the combined exposure to airborne dust and microorganisms was found to be more severe during harvesting than in animal confinements.. agricultural farms| bacteria| dust| fungi|n95 filtering facepiece| organic dust| urinary allergen| air| fungi| buildings| particles| farms| barns| bioaerosols.	MAR-2006	agricultural farms| bacteria| dust| fungi|n95 filtering facepiece| organic dust| urinary allergen| air| fungi| buildings| particles| farms| barns| bioaerosols	Lee, SA; Adhikari, A; Grinshpun, SA; McKay, R; Shukla, R; Reponen, T	Personal exposure to airborne dust and microorganisms in agricultural environments		JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE	agricultural farms; bacteria; dust; fungi	N95 FILTERING FACEPIECE; ORGANIC DUST; URINARY ALLERGEN; AIR; FUNGI; BUILDINGS; PARTICLES; FARMS; BARNS; BIOAEROSOLS	Airborne dust and microorganisms are associated with respiratory diseases and increased mortality, and morbidity. Farmers are at high risk of exposure to both of these hazards. Very limited information, however is available on the combined exposures to both hazards on different types of farms. Moreover most of the previous studies have measured the mass concentration of particles ignoring the particle size. In this study, farmers' exposure to airborne dust and microorganisms was studied using our newly developed personal sampling system. Particle number concentration and size distribution were measured with an optical particle counter Simultaneously, particles were collected on a filter and analyzed for microorganisms. The field measurements were conducted in animal confinements (swine, poultry, and dairy) and during grain harvesting (corn and soybean). The ye concentrations on the results show the following avera workers' breathing zone.- 1. 7 x 10(6) to 2.9 x 10(7) particles/m(3) for total dust, 0.9 x 10(3) to 3.9 x 10(4) spores/m(3) for total fungal spores, 0.3 x 10(3) to 3.6 x 10(4) CFU/m(3) for culturable fungal spores, 0.3 x 10(4) to 3.3 x 10(8) CFU/m(3) for culturable bacteria, and limit of detection (LOD) to 2.8 x 103 CFU/m(3) for culturable actinomycetes in animal confinements. The respective concentrations were 4.4 x 10(6) to 5.8 x 10(7) particles/m(3), 3.4 x 10(4) to 6.1 x 10(6) spores/m(3), 8.2 x 10(4) to 7.4 x 10(6) CFU/m(3), 0.4 x 10(5) to 1.4 x 10(6) CFU/m(3), and LOD to 2.6 x 10(4) CFU/m(3) during grain harvesting. The highest contribution of large particles (3-10 mu m) in total particles was found during grain harvesting, whereas the size distribution was dominated by smaller particles (< 3 mu m) in animal confinements. High fraction (up to 37%) of particles between 2-10 mu m was found to be fungal spores. The results indicate that an increase in the concentration of large dust particles (2-10 mu m) during grain harvesting was partially, attributed to the increase in the concentration of the fungal spores. Overall, the combined exposure to airborne dust and microorganisms was found to be more severe during harvesting than in animal confinements.	48	81	2006	13	10.1080/15459620500524607	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Asthma in Hispanics. Hispanic individuals trace their ancestry to countries that were previously under Spanish rule, including Mexico, large parts of Central and South America, and some Caribbean islands. Most-but not all-Hispanics have variable proportions of European, Amerindian, and African ancestry. Hispanics are diverse with regard to many factors, including racial ancestry, country of origin, area of residence, socioeconomic status, education, and access to health care. Recent findings suggest that there is marked variation in the prevalence, morbidity, and mortality of asthma in Hispanics in the United States and in Hispanic America. The reasons for differences in asthma and asthma morbidity among and within Hispanic subgroups are poorly understood but are likely due to the interaction between yet-unidentified genetic variants and other factors, including environmental tobacco smoke exposure, obesity, allergen exposure, and availability of health care. Barriers to optimal management of asthma in Hispanics in the United States and in Hispanic America include inadequate access to health care, suboptimal use of antiinflammatory medications, and lack of reference values for spirometric measures of lung function in many subgroups (e.g., Puerto Ricans). Future studies of asthma in Hispanics should include large samples of subgroups that are well characterized with regard to self-reported ethnicity, country of origin, place of birth, area of residence, and indicators of socioeconomic status. Because Hispanics are disproportionately represented among the poor in the United States, implementation of adequate access to health care and social reforms (e.g., improving housing conditions) would likely have a major impact on reducing asthma morbidity in this population.. asthma| genetics| hispanics| risk factors|body-mass index| genome-wide search| ethnically diverse populations| inner-city children| house-dust mite| beta(2)-adrenergic receptor polymorphisms| community respiratory health| reference spirometric values| immunoglobulin-e levels| puerto-rican children.	JAN 15-2006	asthma| genetics| hispanics| risk factors|body-mass index| genome-wide search| ethnically diverse populations| inner-city children| house-dust mite| beta(2)-adrenergic receptor polymorphisms| community respiratory health| reference spirometric values| immunoglobulin-e levels| puerto-rican children	Hunninghake, GM; Weiss, ST; Celedon, JC	Asthma in Hispanics		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; genetics; Hispanics; risk factors	BODY-MASS INDEX; GENOME-WIDE SEARCH; ETHNICALLY DIVERSE POPULATIONS; INNER-CITY CHILDREN; HOUSE-DUST MITE; BETA(2)-ADRENERGIC RECEPTOR POLYMORPHISMS; COMMUNITY RESPIRATORY HEALTH; REFERENCE SPIROMETRIC VALUES; IMMUNOGLOBULIN-E LEVELS; PUERTO-RICAN CHILDREN	Hispanic individuals trace their ancestry to countries that were previously under Spanish rule, including Mexico, large parts of Central and South America, and some Caribbean islands. Most-but not all-Hispanics have variable proportions of European, Amerindian, and African ancestry. Hispanics are diverse with regard to many factors, including racial ancestry, country of origin, area of residence, socioeconomic status, education, and access to health care. Recent findings suggest that there is marked variation in the prevalence, morbidity, and mortality of asthma in Hispanics in the United States and in Hispanic America. The reasons for differences in asthma and asthma morbidity among and within Hispanic subgroups are poorly understood but are likely due to the interaction between yet-unidentified genetic variants and other factors, including environmental tobacco smoke exposure, obesity, allergen exposure, and availability of health care. Barriers to optimal management of asthma in Hispanics in the United States and in Hispanic America include inadequate access to health care, suboptimal use of antiinflammatory medications, and lack of reference values for spirometric measures of lung function in many subgroups (e.g., Puerto Ricans). Future studies of asthma in Hispanics should include large samples of subgroups that are well characterized with regard to self-reported ethnicity, country of origin, place of birth, area of residence, and indicators of socioeconomic status. Because Hispanics are disproportionately represented among the poor in the United States, implementation of adequate access to health care and social reforms (e.g., improving housing conditions) would likely have a major impact on reducing asthma morbidity in this population.	309	81	2006	21	10.1164/rccm.200508-1232SO	General & Internal Medicine; Respiratory System
Etiology of atopy in infancy: The KOALA Birth Cohort Study. The aim of the KOALA Birth Cohort Study in the Netherlands is to identify factors that influence the clinical expression of atopic disease with a main focus on lifestyle (e.g., anthroposophy, vaccinations, antibiotics, dietary habits, breastfeeding and breast milk composition, intestinal microflora composition, infections during the first year of life, and gene-environment interaction). The recruitment of pregnant women started in October 2000. First, participants with 'conventional lifestyles' (n = 2343) were retrieved from an ongoing prospective cohort study (n = 7020) on pregnancy-related pelvic girdle pain. In addition, pregnant women (n = 491) with 'alternative lifestyles' with regard to child rearing practices, dietary habits (organic, vegetarian), vaccination schemes and/or use of antibiotics, were recruited through organic food shops, anthroposophic doctors and midwives, Steiner schools, and dedicated magazines. All participants were enrolled between 14 and 18 wk of gestation and completed an intake questionnaire on family history of atopy and infant care intentions. Documentation of other relevant variables started in the pregnant mother and covered the first and third trimester as well as early childhood by repeated questionnaires at 14-18, 30, and 34 wk of gestation and 3, 7, 12, and 24 months postpartum. A subgroup of participants, including both conventional and alternative lifestyles, was asked to consent to maternal blood sampling, breast milk and a faecal sample of the infant at I month post-partum, capillary blood at age 1 yr, venous blood and observation of manifestation of atopic dermatitis during home visits at the age of 2 yr (using the UK working party criteria and the severity scoring of atopic dermatitis index), and buccal swabs for DNA isolation from child-parent trios. From the start, ethical approval and informed consent procedures included gene-environment interaction studies. Follow-up at 3 and 7 months post-partum was completed with high response rates (respectively 90% and 88% in the conventional group, and 97% and 97% in the alternative group). The home visits at 2 yr of age will be completed in 2005. Preliminary results show that we have succeeded in recruiting a large population with various lifestyle choices with a fairly large contrast with regard to dietary habits (including organic foods, vegetarian diet), vaccination schemes and/or use of antibiotics. We have also been able to collect a large number of faecal samples (n = 1176) and capillary blood samples at age 1 yr (n = 956). Furthermore, a large proportion of the participants have consented with genetic studies. Mid 2006 we expect to report our first results on the relationship between the various exposures in early life and childhood atopy. An outline of the focus and design of the KOALA Birth Cohort Study is presented.. allergy| etiology| infant| risk factors| lifestyle| breast feeding| human milk| infections| gene-environment| diet| intestinal microbiota| cohort studies|party diagnostic-criteria| anthroposophic life-style| intestinal microflora| fatty-acids| breast-milk| asthma| dermatitis| environment| children| allergy.	DEC-2005	allergy| etiology| infant| risk factors| lifestyle| breast feeding| human milk| infections| gene-environment| diet| intestinal microbiota| cohort studies|party diagnostic-criteria| anthroposophic life-style| intestinal microflora| fatty-acids| breast-milk| asthma| dermatitis| environment| children| allergy	Kummeling, I; Thijs, C; Penders, J; Snijders, BEP; Stelma, F; Reimerink, J; Koopmans, M; Dagnelie, PC; Huber, M; Jansen, MCJF; de Bie, R; van den Brandt, PA	Etiology of atopy in infancy: The KOALA Birth Cohort Study		PEDIATRIC ALLERGY AND IMMUNOLOGY	allergy; etiology; infant; risk factors; lifestyle; breast feeding; human milk; infections; gene-environment; diet; intestinal microbiota; cohort studies	PARTY DIAGNOSTIC-CRITERIA; ANTHROPOSOPHIC LIFE-STYLE; INTESTINAL MICROFLORA; FATTY-ACIDS; BREAST-MILK; ASTHMA; DERMATITIS; ENVIRONMENT; CHILDREN; ALLERGY	The aim of the KOALA Birth Cohort Study in the Netherlands is to identify factors that influence the clinical expression of atopic disease with a main focus on lifestyle (e.g., anthroposophy, vaccinations, antibiotics, dietary habits, breastfeeding and breast milk composition, intestinal microflora composition, infections during the first year of life, and gene-environment interaction). The recruitment of pregnant women started in October 2000. First, participants with 'conventional lifestyles' (n = 2343) were retrieved from an ongoing prospective cohort study (n = 7020) on pregnancy-related pelvic girdle pain. In addition, pregnant women (n = 491) with 'alternative lifestyles' with regard to child rearing practices, dietary habits (organic, vegetarian), vaccination schemes and/or use of antibiotics, were recruited through organic food shops, anthroposophic doctors and midwives, Steiner schools, and dedicated magazines. All participants were enrolled between 14 and 18 wk of gestation and completed an intake questionnaire on family history of atopy and infant care intentions. Documentation of other relevant variables started in the pregnant mother and covered the first and third trimester as well as early childhood by repeated questionnaires at 14-18, 30, and 34 wk of gestation and 3, 7, 12, and 24 months postpartum. A subgroup of participants, including both conventional and alternative lifestyles, was asked to consent to maternal blood sampling, breast milk and a faecal sample of the infant at I month post-partum, capillary blood at age 1 yr, venous blood and observation of manifestation of atopic dermatitis during home visits at the age of 2 yr (using the UK working party criteria and the severity scoring of atopic dermatitis index), and buccal swabs for DNA isolation from child-parent trios. From the start, ethical approval and informed consent procedures included gene-environment interaction studies. Follow-up at 3 and 7 months post-partum was completed with high response rates (respectively 90% and 88% in the conventional group, and 97% and 97% in the alternative group). The home visits at 2 yr of age will be completed in 2005. Preliminary results show that we have succeeded in recruiting a large population with various lifestyle choices with a fairly large contrast with regard to dietary habits (including organic foods, vegetarian diet), vaccination schemes and/or use of antibiotics. We have also been able to collect a large number of faecal samples (n = 1176) and capillary blood samples at age 1 yr (n = 956). Furthermore, a large proportion of the participants have consented with genetic studies. Mid 2006 we expect to report our first results on the relationship between the various exposures in early life and childhood atopy. An outline of the focus and design of the KOALA Birth Cohort Study is presented.	24	81	2005	6	10.1111/j.1399-3038.2005.00333.x	Allergy; Immunology; Pediatrics
African dust clouds are associated with increased paediatric asthma accident and emergency admissions on the Caribbean island of Trinidad. A retrospective ecological study of paediatric asthma patients who attended the Accident and Emergency (A&E) department of the Paediatric Priority Care Facility at the Eric Williams Medical Sciences Complex in relation to Saharan dust visibility and other climatic variables for the period 23 May 2001 to 13 May 2002 was undertaken to determine if there is an association between paediatric A&E asthma visits and Saharan dust cloud cover. A Poisson regression model was used to determine the statistical relationship between acute paediatric asthma A&E visits and Saharan dust cover with and without other variables such as climatic parameters and month. During the study period, there were 2,655 A&E visits for acute asthma. There was an association between increased paediatric asthma admissions and increased Saharan dust cover. The best fitting model estimated that in one month, such as June, a deterioration of visibility due to increased Saharan dust cover from no dust (visibility =16 km) to very dusty (visibility =7 km) would increase a daily admission rate of 7.8 patients to 9.25 when climate variables such as barometric pressure and humidity were kept constant.. saharan dust| paediatric| asthma| accident and emergency| caribbean|west-indies.	JUL-2005	saharan dust| paediatric| asthma| accident and emergency| caribbean|west-indies	Gyan, K; Henry, W; Lacaille, S; Laloo, A; Lamsee-Ebanks, C; McKay, S; Antoine, RM; Monteil, MA	African dust clouds are associated with increased paediatric asthma accident and emergency admissions on the Caribbean island of Trinidad		INTERNATIONAL JOURNAL OF BIOMETEOROLOGY	Saharan dust; paediatric; asthma; accident and emergency; Caribbean	WEST-INDIES	A retrospective ecological study of paediatric asthma patients who attended the Accident and Emergency (A&E) department of the Paediatric Priority Care Facility at the Eric Williams Medical Sciences Complex in relation to Saharan dust visibility and other climatic variables for the period 23 May 2001 to 13 May 2002 was undertaken to determine if there is an association between paediatric A&E asthma visits and Saharan dust cloud cover. A Poisson regression model was used to determine the statistical relationship between acute paediatric asthma A&E visits and Saharan dust cover with and without other variables such as climatic parameters and month. During the study period, there were 2,655 A&E visits for acute asthma. There was an association between increased paediatric asthma admissions and increased Saharan dust cover. The best fitting model estimated that in one month, such as June, a deterioration of visibility due to increased Saharan dust cover from no dust (visibility =16 km) to very dusty (visibility =7 km) would increase a daily admission rate of 7.8 patients to 9.25 when climate variables such as barometric pressure and humidity were kept constant.	14	81	2005	6	10.1007/s00484-005-0257-3	Biophysics; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences; Physiology
Induction, exacerbation and inhibition of allergic and autoimmune diseases by infection. Epidemiological and experimental data suggest that infections or the exposure to non-pathogenic bacteria protect individuals from developing some autoimmune and atopic disorders. Generally, these findings support the 'hygiene hypothesis', which attributes the rise in autoimmune and atopic disorders to a lack of infections that normally keep the immune system balanced by inducing immunoregulation. The suspected key players for infection-mediated immune suppression of autoimmunity and atopy are T regulatory cells and dendritic cells, which produce immunosuppressive cytokines, such as interleukin-10 and transforming growth factor-beta. However, there is also solid evidence suggesting that infections can exacerbate or even directly cause autoimmune and allergic disorders. In this Review, we discuss which type of infections induce, exacerbate or inhibit allergic and autoimmune diseases and point at infection-induced immunological mechanisms influencing the development of autoimmunity and atopy.. respiratory syncytial virus| inflammatory-bowel-disease| calmette-guerin vaccination| helper type-1 responses| central-nervous-system| birch-pollen allergy| regulatory t-cells| airway inflammation| dendritic cells| murine model.	MAY-2005	respiratory syncytial virus| inflammatory-bowel-disease| calmette-guerin vaccination| helper type-1 responses| central-nervous-system| birch-pollen allergy| regulatory t-cells| airway inflammation| dendritic cells| murine model	Kamradt, T; Goggel, R; Erb, KJ	Induction, exacerbation and inhibition of allergic and autoimmune diseases by infection		TRENDS IN IMMUNOLOGY		RESPIRATORY SYNCYTIAL VIRUS; INFLAMMATORY-BOWEL-DISEASE; CALMETTE-GUERIN VACCINATION; HELPER TYPE-1 RESPONSES; CENTRAL-NERVOUS-SYSTEM; BIRCH-POLLEN ALLERGY; REGULATORY T-CELLS; AIRWAY INFLAMMATION; DENDRITIC CELLS; MURINE MODEL	Epidemiological and experimental data suggest that infections or the exposure to non-pathogenic bacteria protect individuals from developing some autoimmune and atopic disorders. Generally, these findings support the 'hygiene hypothesis', which attributes the rise in autoimmune and atopic disorders to a lack of infections that normally keep the immune system balanced by inducing immunoregulation. The suspected key players for infection-mediated immune suppression of autoimmunity and atopy are T regulatory cells and dendritic cells, which produce immunosuppressive cytokines, such as interleukin-10 and transforming growth factor-beta. However, there is also solid evidence suggesting that infections can exacerbate or even directly cause autoimmune and allergic disorders. In this Review, we discuss which type of infections induce, exacerbate or inhibit allergic and autoimmune diseases and point at infection-induced immunological mechanisms influencing the development of autoimmunity and atopy.	78	81	2005	8	10.1016/j.it.2005.03.009	Immunology
Exercise-induced bronchoconstriction: Pathogenesis. There is still active debate on the acute mechanism of exercise-induced bronchoconstriction (EIB). Although it is unlikely that vasoconstriction and hyperemia of the bronchial vasculature are essential events for EIB, it is likely that this vasculature enhances the airway response to dehydration and contributes to the pathogenesis of EIB, particularly in elite athletes. Accumulating evidence suggests that airway smooth muscle (ASM) becomes more sensitive as a result of repeated exposure to bulk plasma in response to airway injury from dehydration. Recent evidence also demonstrates sufficient concentrations of mediators that could affect ASM. Paradoxically, mediator release from mast cells may be enhanced and their contractile effects greater when beta(2)-receptor agonists are taken daily. The effect of drugs that have the potential to reduce microvascular leak and reduce or inhibit release or action of these mediators needs to be investigated in elite athletes.. canine peripheral airways| thermally-induced asthma| cross-country skiers| mast-cell| bronchial hyperresponsiveness| induced bronchospasm| beta(2)-adrenoceptor-mediated responses| nonasthmatic subjects| isocapnic hyperpnea| allergic rhinitis.	MAR-2005	canine peripheral airways| thermally-induced asthma| cross-country skiers| mast-cell| bronchial hyperresponsiveness| induced bronchospasm| beta(2)-adrenoceptor-mediated responses| nonasthmatic subjects| isocapnic hyperpnea| allergic rhinitis	Anderson, SD; Kippelen, P	Exercise-induced bronchoconstriction: Pathogenesis		CURRENT ALLERGY AND ASTHMA REPORTS		CANINE PERIPHERAL AIRWAYS; THERMALLY-INDUCED ASTHMA; CROSS-COUNTRY SKIERS; MAST-CELL; BRONCHIAL HYPERRESPONSIVENESS; INDUCED BRONCHOSPASM; BETA(2)-ADRENOCEPTOR-MEDIATED RESPONSES; NONASTHMATIC SUBJECTS; ISOCAPNIC HYPERPNEA; ALLERGIC RHINITIS	There is still active debate on the acute mechanism of exercise-induced bronchoconstriction (EIB). Although it is unlikely that vasoconstriction and hyperemia of the bronchial vasculature are essential events for EIB, it is likely that this vasculature enhances the airway response to dehydration and contributes to the pathogenesis of EIB, particularly in elite athletes. Accumulating evidence suggests that airway smooth muscle (ASM) becomes more sensitive as a result of repeated exposure to bulk plasma in response to airway injury from dehydration. Recent evidence also demonstrates sufficient concentrations of mediators that could affect ASM. Paradoxically, mediator release from mast cells may be enhanced and their contractile effects greater when beta(2)-receptor agonists are taken daily. The effect of drugs that have the potential to reduce microvascular leak and reduce or inhibit release or action of these mediators needs to be investigated in elite athletes.	54	81	2005	7	10.1007/s11882-005-0084-y	Allergy; Immunology
The epidemiology and genetics of asthma risk associated with air pollution. The occurrence of asthma and allergic diseases has continued to increase in the United States and worldwide, despite general improvements in air quality over the past 40 years. This observation has led many to question whether air quality is truly a significant risk factor in the development and exacerbation of asthma and whether further improvement in air quality is likely to result in improved health outcomes. However, epidemiologic studies have shown that levels of pollutants of less than the current ambient air quality standards still result in exacerbations of asthma and are associated with other morbidities as well. Specific locations, such as living near a roadway, might pose a special exposure risk. Genetic factors almost certainly play a role in determining susceptibility to pollutants, such as including those involved with antioxidant defenses. The best studied of these in the context of air pollution risks are glutathione-S-transferase polymorphisms. Irrespective of whether pollutants contribute to the development of asthma or the well-documented increases in asthma results in more people having pollutant-induced disease, poor air quality in many places remains a significant problem for patients with asthma and allergic disease. A number of public health, pharmaceutical, and nutriceutical interventions might mitigate the effects of pollutant exposure and deserve further study.. air pollution| asthma| genetics| antioxidants|s-transferase m1| environmental tobacco-smoke| diesel exhaust particles| indoor nitrogen-dioxide| childhood asthma| respiratory symptoms| antioxidant supplementation| mexico-city| ozone exposure| lung-function.	FEB-2005	air pollution| asthma| genetics| antioxidants|s-transferase m1| environmental tobacco-smoke| diesel exhaust particles| indoor nitrogen-dioxide| childhood asthma| respiratory symptoms| antioxidant supplementation| mexico-city| ozone exposure| lung-function	Peden, DB	The epidemiology and genetics of asthma risk associated with air pollution		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	air pollution; asthma; genetics; antioxidants	S-TRANSFERASE M1; ENVIRONMENTAL TOBACCO-SMOKE; DIESEL EXHAUST PARTICLES; INDOOR NITROGEN-DIOXIDE; CHILDHOOD ASTHMA; RESPIRATORY SYMPTOMS; ANTIOXIDANT SUPPLEMENTATION; MEXICO-CITY; OZONE EXPOSURE; LUNG-FUNCTION	The occurrence of asthma and allergic diseases has continued to increase in the United States and worldwide, despite general improvements in air quality over the past 40 years. This observation has led many to question whether air quality is truly a significant risk factor in the development and exacerbation of asthma and whether further improvement in air quality is likely to result in improved health outcomes. However, epidemiologic studies have shown that levels of pollutants of less than the current ambient air quality standards still result in exacerbations of asthma and are associated with other morbidities as well. Specific locations, such as living near a roadway, might pose a special exposure risk. Genetic factors almost certainly play a role in determining susceptibility to pollutants, such as including those involved with antioxidant defenses. The best studied of these in the context of air pollution risks are glutathione-S-transferase polymorphisms. Irrespective of whether pollutants contribute to the development of asthma or the well-documented increases in asthma results in more people having pollutant-induced disease, poor air quality in many places remains a significant problem for patients with asthma and allergic disease. A number of public health, pharmaceutical, and nutriceutical interventions might mitigate the effects of pollutant exposure and deserve further study.	62	81	2005	7	10.1016/j.jaci.2004.12.003	Allergy; Immunology
Increasing Amb a 1 content in common ragweed (Ambrosia artemisiifolia) pollen as a function of rising atmospheric CO2 concentration. Although the impact of increasing atmospheric carbon dioxide concentration ([CO2]) on production of common ragweed ( Ambrosia artemisiifolia L.) pollen has been examined in both indoor and outdoor experiments, the relationship between allergen expression and [CO2] is not known. An enzyme-linked immunosorbent assay ( ELISA) was used to quantify Amb a 1, ragweed's major allergen, in protein extracted from pollen of A. artemisiifolia grown at different [CO2] values in a previous experiment. The concentrations used approximated atmospheric pre-industrial conditions (i.e. at the end of the 19th century), current conditions, and the CO2 concentration projected for the middle of the 21st century ( 280, 370 and 600 mu mol mol(-1) CO2, respectively). Although total pollen protein remained unchanged, significant increases in Amb a 1 allergen were observed between pre-industrial and projected future [CO2] and between current and projected future [CO2] (1.8 and 1.6 times, respectively). These data suggest that recent and projected increases in [CO2] could directly increase the allergenicity of ragweed pollen and consequently the prevalence and / or severity of seasonal allergic disease. However, genetic and abiotic factors governing allergen expression will need to be better established to fully understand these data and their implications for public health.. allergenicity| climate change| public health|public-health| climate-change| aeroallergens| allergy| prevalence| missouri| proteins| antigen| asthma.	2005	allergenicity| climate change| public health|public-health| climate-change| aeroallergens| allergy| prevalence| missouri| proteins| antigen| asthma	Singer, BD; Ziska, LH; Frenz, DA; Gebhard, DE; Straka, JG	Increasing Amb a 1 content in common ragweed (Ambrosia artemisiifolia) pollen as a function of rising atmospheric CO2 concentration		FUNCTIONAL PLANT BIOLOGY	allergenicity; climate change; public health	PUBLIC-HEALTH; CLIMATE-CHANGE; AEROALLERGENS; ALLERGY; PREVALENCE; MISSOURI; PROTEINS; ANTIGEN; ASTHMA	Although the impact of increasing atmospheric carbon dioxide concentration ([CO2]) on production of common ragweed ( Ambrosia artemisiifolia L.) pollen has been examined in both indoor and outdoor experiments, the relationship between allergen expression and [CO2] is not known. An enzyme-linked immunosorbent assay ( ELISA) was used to quantify Amb a 1, ragweed's major allergen, in protein extracted from pollen of A. artemisiifolia grown at different [CO2] values in a previous experiment. The concentrations used approximated atmospheric pre-industrial conditions (i.e. at the end of the 19th century), current conditions, and the CO2 concentration projected for the middle of the 21st century ( 280, 370 and 600 mu mol mol(-1) CO2, respectively). Although total pollen protein remained unchanged, significant increases in Amb a 1 allergen were observed between pre-industrial and projected future [CO2] and between current and projected future [CO2] (1.8 and 1.6 times, respectively). These data suggest that recent and projected increases in [CO2] could directly increase the allergenicity of ragweed pollen and consequently the prevalence and / or severity of seasonal allergic disease. However, genetic and abiotic factors governing allergen expression will need to be better established to fully understand these data and their implications for public health.	24	81	2005	4	10.1071/FP05039	Plant Sciences
Geographic variations in the effect of atopy on asthma in the European Community Respiratory Health Study. Background: Atopy has long been related to asthma. The prevalences of both atopy and asthma have shown substantial variation. Objective: We sought to assess geographic variations in the fraction of asthma attributable to IgE sensitization to specific allergens in the European Community Respiratory Health Survey. Methods: A cross-sectional study was undertaken during the years 1991 and 1992 on 13,558 individuals in 36 centers in 16 countries. Asthma was defined in several ways, variously incorporating reported symptoms, bronchial responsiveness to methacholine, and physician diagnosis. Specific IgE against house dust mite (Dermatophagoides pteronyssinus), cat, timothy grass, Cladosporium herbarum, and a local allergen (birch, Parietaria judaica, or ragweed) were measured. Results: The overall attributable fraction (AF) of asthma symptoms caused by atopy was 30% but varied widely between centers, ranging from 4% to 61%. The overall AF increased to 43% when asthma was based on wheezing and bronchial responsiveness, to 45% with a physician diagnosis of asthma, and to 48% when the patient reported more than 12 attacks in the last year. Between centers, the AF for atopy was significantly correlated with the prevalence of atopy among the asthmatic patients (r = 0.91) and with the sensitization to house dust mite (r = 0.64), as well as with the prevalence of asthma among atopic individuals (r = 0.43) and the prevalence of asthma among nonatopic individuals (r = -0.51). Conclusion: The effect of atopy on the prevalence of asthma varies widely between centers, probably because of variations in factors related to the expression of asthma and to the prevalence of sensitization, particularly to house dust mite.. atopy| asthma| attributable fraction| house dust mite| allergens|house-dust mite| bronchial responsiveness| individual allergens| serum ige| sensitization| exposure| risk| association| prevalence| symptoms.	NOV-2004	atopy| asthma| attributable fraction| house dust mite| allergens|house-dust mite| bronchial responsiveness| individual allergens| serum ige| sensitization| exposure| risk| association| prevalence| symptoms	Sunyer, J; Jarvis, D; Pekkanen, J; Chinn, S; Janson, C; Leynaert, B; Luczynska, C; Garcia-Esteban, R; Burney, P; Anto, JM	Geographic variations in the effect of atopy on asthma in the European Community Respiratory Health Study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopy; asthma; attributable fraction; house dust mite; allergens	HOUSE-DUST MITE; BRONCHIAL RESPONSIVENESS; INDIVIDUAL ALLERGENS; SERUM IGE; SENSITIZATION; EXPOSURE; RISK; ASSOCIATION; PREVALENCE; SYMPTOMS	Background: Atopy has long been related to asthma. The prevalences of both atopy and asthma have shown substantial variation. Objective: We sought to assess geographic variations in the fraction of asthma attributable to IgE sensitization to specific allergens in the European Community Respiratory Health Survey. Methods: A cross-sectional study was undertaken during the years 1991 and 1992 on 13,558 individuals in 36 centers in 16 countries. Asthma was defined in several ways, variously incorporating reported symptoms, bronchial responsiveness to methacholine, and physician diagnosis. Specific IgE against house dust mite (Dermatophagoides pteronyssinus), cat, timothy grass, Cladosporium herbarum, and a local allergen (birch, Parietaria judaica, or ragweed) were measured. Results: The overall attributable fraction (AF) of asthma symptoms caused by atopy was 30% but varied widely between centers, ranging from 4% to 61%. The overall AF increased to 43% when asthma was based on wheezing and bronchial responsiveness, to 45% with a physician diagnosis of asthma, and to 48% when the patient reported more than 12 attacks in the last year. Between centers, the AF for atopy was significantly correlated with the prevalence of atopy among the asthmatic patients (r = 0.91) and with the sensitization to house dust mite (r = 0.64), as well as with the prevalence of asthma among atopic individuals (r = 0.43) and the prevalence of asthma among nonatopic individuals (r = -0.51). Conclusion: The effect of atopy on the prevalence of asthma varies widely between centers, probably because of variations in factors related to the expression of asthma and to the prevalence of sensitization, particularly to house dust mite.	26	81	2004	7	10.1016/j.jaci.2004.05.072	Allergy; Immunology
Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells. In horses prone to developing recurrent airway obstruction (RAO), we tested the hypotheses that the cytokine profile in the bronchoalveolar lavage (BAL) cells of affected horses would reflect a polarized Th-2 response; that cytokine and chemokine alterations would occur within 24 h of allergen exposure; and that allergen exposure would induce alterations in the expression of the transcription factor t-bet (t-box-expressed in T-cells). The expression levels of interleukin-4 (IL-4), IL-13, Interferongamma (IFN-gamma). t-bet, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) were measured in BAL cells obtained from control and RAO-susceptible horses during an asymptomatic phase and at 24 It and 5 weeks post-stabling and hay exposure. At each sampling time, BAL neutrophil percentages in the RAO-group exceeded controls. In the RAO-group, only IL-13 expression was decreased 2-fold during the asymptomatic phase. No differences in cytokine or chemokine expression were detected during the acute exposure phase. During the chronic phase, IFN-gamma and IL-8 expression levels were 2.5- and 3-fold greater, respectively, in the RAO-group. No other differences in gene expression were detected. We conclude that the cytokine profile of the airway cells does not reflect a polarized Th-2 response; that increases in IFN-gamma result from a t-bet independent pathway and that chemokines from epithelial or interstitial cells may contribute to early neutrophil influx. (C) 2003 Elsevier B.V. All rights reserved.. cytokine horse| rao| heaves| t-bet| ifn-gamma|pulmonary-disease copd| interferon-gamma| phenotypic analysis| antibody-responses| fluid lymphocytes| peripheral-blood| messenger-rna| heaves horses| t-bet| chemokines.	NOV 15-2003	cytokine horse| rao| heaves| t-bet| ifn-gamma|pulmonary-disease copd| interferon-gamma| phenotypic analysis| antibody-responses| fluid lymphocytes| peripheral-blood| messenger-rna| heaves horses| t-bet| chemokines	Ainsworth, DM; Grunig, G; Matychak, MB; Young, J; Wagner, B; Erb, HN; Antczak, DF	Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells		VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY	cytokine horse; RAO; heaves; t-bet; IFN-gamma	PULMONARY-DISEASE COPD; INTERFERON-GAMMA; PHENOTYPIC ANALYSIS; ANTIBODY-RESPONSES; FLUID LYMPHOCYTES; PERIPHERAL-BLOOD; MESSENGER-RNA; HEAVES HORSES; T-BET; CHEMOKINES	In horses prone to developing recurrent airway obstruction (RAO), we tested the hypotheses that the cytokine profile in the bronchoalveolar lavage (BAL) cells of affected horses would reflect a polarized Th-2 response; that cytokine and chemokine alterations would occur within 24 h of allergen exposure; and that allergen exposure would induce alterations in the expression of the transcription factor t-bet (t-box-expressed in T-cells). The expression levels of interleukin-4 (IL-4), IL-13, Interferongamma (IFN-gamma). t-bet, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF) were measured in BAL cells obtained from control and RAO-susceptible horses during an asymptomatic phase and at 24 It and 5 weeks post-stabling and hay exposure. At each sampling time, BAL neutrophil percentages in the RAO-group exceeded controls. In the RAO-group, only IL-13 expression was decreased 2-fold during the asymptomatic phase. No differences in cytokine or chemokine expression were detected during the acute exposure phase. During the chronic phase, IFN-gamma and IL-8 expression levels were 2.5- and 3-fold greater, respectively, in the RAO-group. No other differences in gene expression were detected. We conclude that the cytokine profile of the airway cells does not reflect a polarized Th-2 response; that increases in IFN-gamma result from a t-bet independent pathway and that chemokines from epithelial or interstitial cells may contribute to early neutrophil influx. (C) 2003 Elsevier B.V. All rights reserved.	33	81	2003	9	10.1016/S0165-2427(03)00142-9	Immunology; Veterinary Sciences
Reproducibility of allergen, endotoxin and fungi measurements in the indoor environment. Measurements of biocontaminants in settled house dust once a year are commonly used to assess long-term exposure. To examine stability over time and seasonal variation, we measured concentrations of mite and cat allergens, endotoxin and mold spores in living room floor dust in 745 German homes collected twice a year in two different seasons. The study population consisted of adults and children living in five different areas in Germany. All dust samples were collected in a standardized manner from the living room floor and taken during the years 1995 to 1998. The median interval between the two dust samplings was approximately 7 months. Mite and cat allergens were measured in settled house dust by monoclonal antibodies, endotoxin by the limulus amebocyte lysate method, and total spore counts by cultural methods. Crude Pearson's correlation coefficients between log-transformed concentrations in the first and second dust samples ranged between 0.65 and 0.75 for allergens, 0.59 for endotoxin and only 0.06 for total spore counts. The strongest and most consistent seasonal effects were observed for fungi with highest levels in July-September. Cat allergen concentrations were found consistently to be increased in January-March. Mite allergens did not show a strong and consistent seasonal pattern. We conclude that repeated measurements of mite and cat allergens and endotoxin in settled house dust improve the estimate for annual mean concentrations. However, even a single observation of these biocontaminants may be a good proxy for a 1-year exposure since repeated measures were highly correlated. However, repeated measurements of fungi levels were only weakly correlated and thus repeated observations for assessment of annual means of total spore counts are needed.. reproducibility| house dust mite| cat| allergen| endotoxin| house dust| fungi|house-dust mite| respiratory symptoms| extracellular polysaccharides| culturable fungi| 2 cities| exposure| asthma| sensitization| children| germany.	MAR-2003	reproducibility| house dust mite| cat| allergen| endotoxin| house dust| fungi|house-dust mite| respiratory symptoms| extracellular polysaccharides| culturable fungi| 2 cities| exposure| asthma| sensitization| children| germany	Heinrich, J; Holscher, B; Douwes, J; Richter, K; Koch, A; Bischof, W; Fahlbusch, B; Kinne, RW; Wichmann, HE	Reproducibility of allergen, endotoxin and fungi measurements in the indoor environment		JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY	reproducibility; house dust mite; cat; allergen; endotoxin; house dust; fungi	HOUSE-DUST MITE; RESPIRATORY SYMPTOMS; EXTRACELLULAR POLYSACCHARIDES; CULTURABLE FUNGI; 2 CITIES; EXPOSURE; ASTHMA; SENSITIZATION; CHILDREN; GERMANY	Measurements of biocontaminants in settled house dust once a year are commonly used to assess long-term exposure. To examine stability over time and seasonal variation, we measured concentrations of mite and cat allergens, endotoxin and mold spores in living room floor dust in 745 German homes collected twice a year in two different seasons. The study population consisted of adults and children living in five different areas in Germany. All dust samples were collected in a standardized manner from the living room floor and taken during the years 1995 to 1998. The median interval between the two dust samplings was approximately 7 months. Mite and cat allergens were measured in settled house dust by monoclonal antibodies, endotoxin by the limulus amebocyte lysate method, and total spore counts by cultural methods. Crude Pearson's correlation coefficients between log-transformed concentrations in the first and second dust samples ranged between 0.65 and 0.75 for allergens, 0.59 for endotoxin and only 0.06 for total spore counts. The strongest and most consistent seasonal effects were observed for fungi with highest levels in July-September. Cat allergen concentrations were found consistently to be increased in January-March. Mite allergens did not show a strong and consistent seasonal pattern. We conclude that repeated measurements of mite and cat allergens and endotoxin in settled house dust improve the estimate for annual mean concentrations. However, even a single observation of these biocontaminants may be a good proxy for a 1-year exposure since repeated measures were highly correlated. However, repeated measurements of fungi levels were only weakly correlated and thus repeated observations for assessment of annual means of total spore counts are needed.	39	81	2003	9	10.1038/sj.jea.7500267	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Late adverse reactions to intravascular iodinated contrast media. Late adverse reactions to intravascular iodinated contrast media are defined as reactions occurring 1 h to 1 week after contrast medium injection. They have received increasing interest over the past decade, but their prevalence remains uncertain and their pathophysiology is not fully understood. The Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and to issue guidelines. An extensive literature search was carried out and summarized in a report. Based on the available information, simple guidelines have been drawn up. The report and guidelines were discussed at the 8th European Symposium on Urogenital Radiology in Genoa. Late adverse reactions after intravascular iodinated contrast medium include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. A significant proportion of these reactions is unrelated to the contrast medium; however, allergy-like skin reactions are well-documented side effects of contrast media with an incidence of approximately 2%. Late reactions appear to be commoner after nonionic dimers. The majority of late skin reactions after contrast medium exposure are probably T cell-mediated allergic reactions. Patients at increased risk of late skin reactions are those with a history of previous contrast medium reaction and those on interluekin-2 treatment. Most skin reactions are self-limiting and resolve within a week. Management is symptomatic and similar to the management of other drug-induced skin reactions.. iodinated contrast media| late adverse reactions|allergy-like reactions| delayed-reactions| interleukin-2| hypersensitivity| immediate| urography| iopamidol| vasculitis| ioxaglate| iodixanol.	JAN-2003	iodinated contrast media| late adverse reactions|allergy-like reactions| delayed-reactions| interleukin-2| hypersensitivity| immediate| urography| iopamidol| vasculitis| ioxaglate| iodixanol	Webb, JAW; Stacul, F; Thomsen, HS; Morcos, SK	Late adverse reactions to intravascular iodinated contrast media		EUROPEAN RADIOLOGY	iodinated contrast media; late adverse reactions	ALLERGY-LIKE REACTIONS; DELAYED-REACTIONS; INTERLEUKIN-2; HYPERSENSITIVITY; IMMEDIATE; UROGRAPHY; IOPAMIDOL; VASCULITIS; IOXAGLATE; IODIXANOL	Late adverse reactions to intravascular iodinated contrast media are defined as reactions occurring 1 h to 1 week after contrast medium injection. They have received increasing interest over the past decade, but their prevalence remains uncertain and their pathophysiology is not fully understood. The Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and to issue guidelines. An extensive literature search was carried out and summarized in a report. Based on the available information, simple guidelines have been drawn up. The report and guidelines were discussed at the 8th European Symposium on Urogenital Radiology in Genoa. Late adverse reactions after intravascular iodinated contrast medium include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. A significant proportion of these reactions is unrelated to the contrast medium; however, allergy-like skin reactions are well-documented side effects of contrast media with an incidence of approximately 2%. Late reactions appear to be commoner after nonionic dimers. The majority of late skin reactions after contrast medium exposure are probably T cell-mediated allergic reactions. Patients at increased risk of late skin reactions are those with a history of previous contrast medium reaction and those on interluekin-2 treatment. Most skin reactions are self-limiting and resolve within a week. Management is symptomatic and similar to the management of other drug-induced skin reactions.	43	81	2003	4	10.1007/s00330-002-1650-5	Radiology, Nuclear Medicine & Medical Imaging
Levels of household mold associated with respiratory symptoms in the first year of life in a cohort at risk for asthma. We assessed prospectively the risk of increased incidence of respiratory symptoms after exposure to particular fungal genera in a susceptible population-namely, infants (n = 880) at high risk for developing asthma. Days of wheeze or persistent cough, information on maternal allergy and asthma, socioeconomic variables, and housing characteristics were collected over the course of the infant's first year of life. Exposure to mold was assessed by airborne samples collected at one time early in the infant's life. Fungi were identified to genus level, recorded as colony-forming units per cubic meter (CFU/m(3)), and then categorized into four levels: 0 (undetectable), 1-499 CFU/m(3) (low), 500-999 CFU/m(3) (medium), and 1,000 CFU/m(3) (high). Effects of mold on wheeze and persistent cough, adjusting for potential confounding factors, were examined with Poisson regression analyses. The two most commonly found genera were Cladosporium (in 62% of the homes) and Penicillium (41%). Cladosporium was associated with reported mold (p < 0.02) and water leaks (p < 0.003). Rate of persistent cough was associated with reported mold [Rate ratio (RR) = 1.49; 95% CI, 1.18-1.88]. The highest level of Penicillium was associated with higher rates of wheeze (RR = 2.15; 95% CI, 1.34-3.46) and persistent cough (RR = 2.06; 95% CI, 1.31-3.24) in models controlling for maternal history of asthma and allergy, socioeconomic status, season of mold sample, and certain housing characteristics. We conclude that infants in this high-risk group who are exposed to high levels of Penicillium are at significant risk for wheeze and persistent cough.. asthma| fungi| indoor air| infants| mold| penicillium| wheezing|fungal extracellular polysaccharides| culturable fungi| dust mites| indoor-air| health| children| exposure| homes| damp| prevalence.	DEC-2002	asthma| fungi| indoor air| infants| mold| penicillium| wheezing|fungal extracellular polysaccharides| culturable fungi| dust mites| indoor-air| health| children| exposure| homes| damp| prevalence	Gent, JF; Ren, P; Belanger, K; Triche, E; Bracken, MB; Holford, TR; Leaderer, BP	Levels of household mold associated with respiratory symptoms in the first year of life in a cohort at risk for asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; fungi; indoor air; infants; mold; Penicillium; wheezing	FUNGAL EXTRACELLULAR POLYSACCHARIDES; CULTURABLE FUNGI; DUST MITES; INDOOR-AIR; HEALTH; CHILDREN; EXPOSURE; HOMES; DAMP; PREVALENCE	We assessed prospectively the risk of increased incidence of respiratory symptoms after exposure to particular fungal genera in a susceptible population-namely, infants (n = 880) at high risk for developing asthma. Days of wheeze or persistent cough, information on maternal allergy and asthma, socioeconomic variables, and housing characteristics were collected over the course of the infant's first year of life. Exposure to mold was assessed by airborne samples collected at one time early in the infant's life. Fungi were identified to genus level, recorded as colony-forming units per cubic meter (CFU/m(3)), and then categorized into four levels: 0 (undetectable), 1-499 CFU/m(3) (low), 500-999 CFU/m(3) (medium), and 1,000 CFU/m(3) (high). Effects of mold on wheeze and persistent cough, adjusting for potential confounding factors, were examined with Poisson regression analyses. The two most commonly found genera were Cladosporium (in 62% of the homes) and Penicillium (41%). Cladosporium was associated with reported mold (p < 0.02) and water leaks (p < 0.003). Rate of persistent cough was associated with reported mold [Rate ratio (RR) = 1.49; 95% CI, 1.18-1.88]. The highest level of Penicillium was associated with higher rates of wheeze (RR = 2.15; 95% CI, 1.34-3.46) and persistent cough (RR = 2.06; 95% CI, 1.31-3.24) in models controlling for maternal history of asthma and allergy, socioeconomic status, season of mold sample, and certain housing characteristics. We conclude that infants in this high-risk group who are exposed to high levels of Penicillium are at significant risk for wheeze and persistent cough.	31	81	2002	6		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Interleukin-13 induces proliferation of human airway epithelial cells in vitro via a mechanism mediated by transforming growth factor-alpha. Remodeling of the airways, as occurs in asthmatic patients, is associated with the continual presence of inflammatory mediators and Th2 cytokines, especially interleukin (IL)-13, during cycles of epithelial injury and repair. In this study, we examined the effect of IL-13 on well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture. IL-13 induced proliferation of NHBE cells after 24 h exposure, as reflected by [H-3]thymidine uptake and cell counts. The effects of IL-13 were mediated through the epidermal growth factor receptor (EGFR), as proliferation was attenuated by AG1478, an EGFR tyrosine kinase inhibitor. Proliferation appeared to be mediated by transforming growth factor (TGF)-alpha, a potent ligand for EGFR, which was released rapidly from NHBE cells in response to IL-13. Neutralizing antibody to TGF-alpha, but not antibodies against other potentially important growth factors (EGF, heparin binding epidermal growth factor-like growth factor [HB-EGF], platelet-derived growth factor [PDGF]), inhibited the mitogenic response to IL-13. This study provides the first experimental evidence that IL-13 can initiate a proliferative response of human airway epithelium in the absence of inflammatory cells or other cell types. The results are consistent with a mechanism whereby IL-13 induces release of TGF-alpha from the epithelial cells, which in turn binds via an autocrine/paracrine-type action to the EGFR, initiating proliferation. IL-13-induced airway remodeling in vivo may involve this epithelium-driven response.. factor-receptor| in-vitro| egf-receptor| expression| injury| rats| asthma| lung.	DEC-2001	factor-receptor| in-vitro| egf-receptor| expression| injury| rats| asthma| lung	Booth, BW; Adler, KB; Bonner, JC; Tournier, F; Martin, LD	Interleukin-13 induces proliferation of human airway epithelial cells in vitro via a mechanism mediated by transforming growth factor-alpha		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		FACTOR-RECEPTOR; IN-VITRO; EGF-RECEPTOR; EXPRESSION; INJURY; RATS; ASTHMA; LUNG	Remodeling of the airways, as occurs in asthmatic patients, is associated with the continual presence of inflammatory mediators and Th2 cytokines, especially interleukin (IL)-13, during cycles of epithelial injury and repair. In this study, we examined the effect of IL-13 on well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture. IL-13 induced proliferation of NHBE cells after 24 h exposure, as reflected by [H-3]thymidine uptake and cell counts. The effects of IL-13 were mediated through the epidermal growth factor receptor (EGFR), as proliferation was attenuated by AG1478, an EGFR tyrosine kinase inhibitor. Proliferation appeared to be mediated by transforming growth factor (TGF)-alpha, a potent ligand for EGFR, which was released rapidly from NHBE cells in response to IL-13. Neutralizing antibody to TGF-alpha, but not antibodies against other potentially important growth factors (EGF, heparin binding epidermal growth factor-like growth factor [HB-EGF], platelet-derived growth factor [PDGF]), inhibited the mitogenic response to IL-13. This study provides the first experimental evidence that IL-13 can initiate a proliferative response of human airway epithelium in the absence of inflammatory cells or other cell types. The results are consistent with a mechanism whereby IL-13 induces release of TGF-alpha from the epithelial cells, which in turn binds via an autocrine/paracrine-type action to the EGFR, initiating proliferation. IL-13-induced airway remodeling in vivo may involve this epithelium-driven response.	31	81	2001	5		Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Characterization and cloning of a major high molecular weight house dust mite allergen (Der f 15) for dogs. Although house dust mites (HDM(s)) are important elicitors of canine allergy, the low molecular weight molecules defined as major allergens for humans do not appear to be major allergens for dogs. Western blotting of Dermatophagoides farinae (D. farinae) extracts with sera from sensitized dogs showed that the majority of animals had IgE antibodies specific for two proteins of apparent molecular weights of 98 and 109 kDa (98/109 kDa). The N-terminal sequences of these two proteins were identical, suggesting they were very closely related, and sequencing of internal peptides showed the protein(s) to have homology with insect chitinases. A purified preparation of 98/109 kDa proteins elicited positive intradermal skin tests (IDST(s)) in a group of well-characterized atopic dogs sensitized to D. farinae, but not in normal dogs. A rabbit polyclonal antiserum raised against the purified proteins was used to immunoscreen a D. farinae cDNA library. The mature coding region of the isolated chitinase cDNA predicts a protein of 63.2 kDa; sequence analysis and glycan detection blotting suggest that the molecule is extensively O-glycosylated. Monoclonal antibodies made against the purified native protein were used to localize the chitinase in sections of whole D. farinae mites. The protein displayed an intracellular distribution in the proventriculus and intestine of the mite, suggesting that it has a digestive, rather than a moulting-related, function. The high prevalence of IgE antibodies to this antigen in canine atopic dermatitis makes it a major HDM allergen for dogs, and the protein has been formally designated Der f 15. (C) 2001 Elsevier Science B.V. All rights reserved.. atopic dermatitis| mite allergen| allergen| dog| ige|dermatophagoides-farinae| ige| canine| reactivity| chitinases| extracts| protein| family| sites.	FEB 10-2001	atopic dermatitis| mite allergen| allergen| dog| ige|dermatophagoides-farinae| ige| canine| reactivity| chitinases| extracts| protein| family| sites	McCall, C; Hunter, S; Stedman, K; Weber, E; Hillier, A; Bozic, C; Rivoire, B; Olivry, T	Characterization and cloning of a major high molecular weight house dust mite allergen (Der f 15) for dogs		VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY	atopic dermatitis; mite allergen; allergen; dog; IgE	DERMATOPHAGOIDES-FARINAE; IGE; CANINE; REACTIVITY; CHITINASES; EXTRACTS; PROTEIN; FAMILY; SITES	Although house dust mites (HDM(s)) are important elicitors of canine allergy, the low molecular weight molecules defined as major allergens for humans do not appear to be major allergens for dogs. Western blotting of Dermatophagoides farinae (D. farinae) extracts with sera from sensitized dogs showed that the majority of animals had IgE antibodies specific for two proteins of apparent molecular weights of 98 and 109 kDa (98/109 kDa). The N-terminal sequences of these two proteins were identical, suggesting they were very closely related, and sequencing of internal peptides showed the protein(s) to have homology with insect chitinases. A purified preparation of 98/109 kDa proteins elicited positive intradermal skin tests (IDST(s)) in a group of well-characterized atopic dogs sensitized to D. farinae, but not in normal dogs. A rabbit polyclonal antiserum raised against the purified proteins was used to immunoscreen a D. farinae cDNA library. The mature coding region of the isolated chitinase cDNA predicts a protein of 63.2 kDa; sequence analysis and glycan detection blotting suggest that the molecule is extensively O-glycosylated. Monoclonal antibodies made against the purified native protein were used to localize the chitinase in sections of whole D. farinae mites. The protein displayed an intracellular distribution in the proventriculus and intestine of the mite, suggesting that it has a digestive, rather than a moulting-related, function. The high prevalence of IgE antibodies to this antigen in canine atopic dermatitis makes it a major HDM allergen for dogs, and the protein has been formally designated Der f 15. (C) 2001 Elsevier Science B.V. All rights reserved.	26	81	2001	17	10.1016/S0165-2427(00)00258-0	Immunology; Veterinary Sciences
Predictors of asthma three years after hospital admission for wheezing in infancy. Objective. To evaluate the influence of early antiinflammatory therapy in the development of asthma 3 years after hospitalization for wheezing in infancy. In addition, the effects of allergic sensitization and respiratory syncytial virus (RSV) infection on the development of asthma were investigated. Design and Setting. A randomized, controlled follow-up study in a university hospital that provides primary hospital care for all pediatric patients in a defined area. Patients. Eighty-nine infants under 2 years of age who had been hospitalized for infection associated with wheezing and followed up for 3 years. Intervention. Early antiinflammatory therapy was given for 16 weeks; 29 patients received cromolyn sodium and 31 received budesonide. Twenty-nine control patients received no therapy. Outcome Measures. Clinical diagnosis of current asthma, defined as having at least 3 episodes of physician-diagnosed wheezing and either a wheezing episode during the preceding year or ongoing antiinflammatory medication for asthma. Results. Fourteen (48%) patients in the former cromolyn group, 15 (48%) in the former budesonide group, and 16 (55%) in the control group had current asthma. The significant predictors of asthma were age over 12 months (risk ratio [RR] 4.1; 95% confidence interval [CI] = 1.59-10.35), history of wheezing (RR 6.8; CI = 1.35-34.43), and atopic dermatitis on study entry (RR 3.4; CI = 1.17-9.39). Skin prick test positivity at the age of 16 months significantly predicted asthma (RR 9.5; CI = 2.45-36.72). In addition, all of the 18 (20%) children sensitized with furred pet developed asthma. RSV identification (RR 0.3; CI = 0.08-0.80) and early furred pet contact at home (RR 0.3; CI 0.10-0.79) were associated with the decreased occurrence of asthma. Conclusions. Antiinflammatory therapy for 4 months has no influence on the occurrence of asthma 3 years after wheezing in infancy. Early sensitization to indoor allergens, especially to pets, and atopic dermatitis predict subsequent development of asthma. RSV infection in wheezing infants may have a better outcome than other infections.. asthma| atopy| budesonide| child| cromlyn sodium| follow-up study| infant| immunoglobulin e| respiratory syncytial virus| risk factors| sensitization| wheezing| virus diseases|respiratory syncytial virus| environmental risk-factors| acute viral bronchiolitis| follow-up| lung-function| bronchial-asthma| childhood asthma| immunoglobulin-e| hay-fever| children.	DEC-2000	asthma| atopy| budesonide| child| cromlyn sodium| follow-up study| infant| immunoglobulin e| respiratory syncytial virus| risk factors| sensitization| wheezing| virus diseases|respiratory syncytial virus| environmental risk-factors| acute viral bronchiolitis| follow-up| lung-function| bronchial-asthma| childhood asthma| immunoglobulin-e| hay-fever| children	Reijonen, TM; Kotaniemi-Syrjanen, A; Korhonen, K; Korppi, M	Predictors of asthma three years after hospital admission for wheezing in infancy		PEDIATRICS	asthma; atopy; budesonide; child; cromlyn sodium; follow-up study; infant; immunoglobulin E; respiratory syncytial virus; risk factors; sensitization; wheezing; virus diseases	RESPIRATORY SYNCYTIAL VIRUS; ENVIRONMENTAL RISK-FACTORS; ACUTE VIRAL BRONCHIOLITIS; FOLLOW-UP; LUNG-FUNCTION; BRONCHIAL-ASTHMA; CHILDHOOD ASTHMA; IMMUNOGLOBULIN-E; HAY-FEVER; CHILDREN	Objective. To evaluate the influence of early antiinflammatory therapy in the development of asthma 3 years after hospitalization for wheezing in infancy. In addition, the effects of allergic sensitization and respiratory syncytial virus (RSV) infection on the development of asthma were investigated. Design and Setting. A randomized, controlled follow-up study in a university hospital that provides primary hospital care for all pediatric patients in a defined area. Patients. Eighty-nine infants under 2 years of age who had been hospitalized for infection associated with wheezing and followed up for 3 years. Intervention. Early antiinflammatory therapy was given for 16 weeks; 29 patients received cromolyn sodium and 31 received budesonide. Twenty-nine control patients received no therapy. Outcome Measures. Clinical diagnosis of current asthma, defined as having at least 3 episodes of physician-diagnosed wheezing and either a wheezing episode during the preceding year or ongoing antiinflammatory medication for asthma. Results. Fourteen (48%) patients in the former cromolyn group, 15 (48%) in the former budesonide group, and 16 (55%) in the control group had current asthma. The significant predictors of asthma were age over 12 months (risk ratio [RR] 4.1; 95% confidence interval [CI] = 1.59-10.35), history of wheezing (RR 6.8; CI = 1.35-34.43), and atopic dermatitis on study entry (RR 3.4; CI = 1.17-9.39). Skin prick test positivity at the age of 16 months significantly predicted asthma (RR 9.5; CI = 2.45-36.72). In addition, all of the 18 (20%) children sensitized with furred pet developed asthma. RSV identification (RR 0.3; CI = 0.08-0.80) and early furred pet contact at home (RR 0.3; CI 0.10-0.79) were associated with the decreased occurrence of asthma. Conclusions. Antiinflammatory therapy for 4 months has no influence on the occurrence of asthma 3 years after wheezing in infancy. Early sensitization to indoor allergens, especially to pets, and atopic dermatitis predict subsequent development of asthma. RSV infection in wheezing infants may have a better outcome than other infections.	35	81	2000	7	10.1542/peds.106.6.1406	Pediatrics
Asthma-like symptoms in wood product plant workers exposed to methylene diphenyl diisocyanate. Background: Diisocyanates, a group of highly reactive chemicals, have frequently been associated with occupational asthma. We evaluated respiratory health in workers at a new wood products manufacturing plant that uses methylene diphenyl diisocyanate (MDI), and was designed and operated with a goal of minimizing worker exposures, Methods: Health surveys using standardized respiratory questionnaires were done prior to the initial use of diisocyanates in the plant, and semiannually thereafter for a period of 2 years. Other testing included occupational and work practice histories, serial peak flow measurements, spirometry, methacholine challenge, and measurement of specific IgE antibodies to MDI-albumin conjugate. Results: Of 214 plant employees who participated in at least one health survey, a follow-up survey was also available from 178 employees (83%). New-onset asthma-like symptoms (NAS) were reported by 15 of 56 workers (27%) in areas with the highest potential for exposures to liquid MDI monomer and prepolymer, vs 0 of 43 workers in the lowest potential exposure areas (p = 0.001). In the areas with high potential exposure, NAS developed in 47% of workers who had noted MDI skin staining, vs 19% without skin stains (p = 0.07), Working around and cleaning up liquid MDI represented a significant risk for asthma-like symptoms in both current smokers and nonsmokers; work with finished wood products did not. Asthma-like symptoms were associated with variable airflow limitation (odds ratio [OR], 5.0; confidence interval [CI], 1.4 to 18.7) and specific IgE to MDI-albumin (OR, 3.2; CI, 1.1 to 9.0), but not with skin prick tests to common aeroallergens (OR, 1.1; CI, 0.5 to 2.7), Conclusions: During the first 2 years of operation, in a plant designed and operated to control exposure to diisocyanates, the development of asthma-like symptoms was reported in a relatively high proportion of the employees who worked with liquid MDI. To prevent asthma symptoms among workers, careful control of respiratory tract exposures associated with liquid MDI is important, especially during cleanup activities. Strict limitation of skin contact with diisocyanates may also be necessary.. asthma| diisocyanates| occupational asthma| respiratory protection| skin exposure| wood products|occupational asthma| surveillance system| isocyanates| methacholine| population| challenge| responses| diseases| mdi.	OCT-2000	asthma| diisocyanates| occupational asthma| respiratory protection| skin exposure| wood products|occupational asthma| surveillance system| isocyanates| methacholine| population| challenge| responses| diseases| mdi	Petsonk, EL; Wang, ML; Lewis, DM; Siegel, PD; Husberg, BJ	Asthma-like symptoms in wood product plant workers exposed to methylene diphenyl diisocyanate		CHEST	asthma; diisocyanates; occupational asthma; respiratory protection; skin exposure; wood products	OCCUPATIONAL ASTHMA; SURVEILLANCE SYSTEM; ISOCYANATES; METHACHOLINE; POPULATION; CHALLENGE; RESPONSES; DISEASES; MDI	Background: Diisocyanates, a group of highly reactive chemicals, have frequently been associated with occupational asthma. We evaluated respiratory health in workers at a new wood products manufacturing plant that uses methylene diphenyl diisocyanate (MDI), and was designed and operated with a goal of minimizing worker exposures, Methods: Health surveys using standardized respiratory questionnaires were done prior to the initial use of diisocyanates in the plant, and semiannually thereafter for a period of 2 years. Other testing included occupational and work practice histories, serial peak flow measurements, spirometry, methacholine challenge, and measurement of specific IgE antibodies to MDI-albumin conjugate. Results: Of 214 plant employees who participated in at least one health survey, a follow-up survey was also available from 178 employees (83%). New-onset asthma-like symptoms (NAS) were reported by 15 of 56 workers (27%) in areas with the highest potential for exposures to liquid MDI monomer and prepolymer, vs 0 of 43 workers in the lowest potential exposure areas (p = 0.001). In the areas with high potential exposure, NAS developed in 47% of workers who had noted MDI skin staining, vs 19% without skin stains (p = 0.07), Working around and cleaning up liquid MDI represented a significant risk for asthma-like symptoms in both current smokers and nonsmokers; work with finished wood products did not. Asthma-like symptoms were associated with variable airflow limitation (odds ratio [OR], 5.0; confidence interval [CI], 1.4 to 18.7) and specific IgE to MDI-albumin (OR, 3.2; CI, 1.1 to 9.0), but not with skin prick tests to common aeroallergens (OR, 1.1; CI, 0.5 to 2.7), Conclusions: During the first 2 years of operation, in a plant designed and operated to control exposure to diisocyanates, the development of asthma-like symptoms was reported in a relatively high proportion of the employees who worked with liquid MDI. To prevent asthma symptoms among workers, careful control of respiratory tract exposures associated with liquid MDI is important, especially during cleanup activities. Strict limitation of skin contact with diisocyanates may also be necessary.	33	81	2000	15	10.1378/chest.118.4.1183	General & Internal Medicine; Respiratory System
Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma. When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 mu g bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV1) greater than or equal to 70% predicted; EIB greater than or equal to 20% fall in FEV1 from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were rerandomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV1 from baseline) and methacholine challenge using a dosimetric technique (expressed as PD20) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV1 being reduced from 34.1% to 9.9% for 100 mu g FP bid, and from 35.9% to 7.6% for 250 mu g FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD20 methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 mu g FP bid, 1.6 dose steps; 250 mu g FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment. (C) 2000 Wiley-Liss, Inc.. exercise-induced asthma| bronchial hyperresponsiveness| inhaled corticosteroids| fluticasone propionate| eosinophil cationic protein| randomized clinical trial| children|working party standardization| european respiratory society| cationic protein ecp| bronchial hyperresponsiveness| lung-function| airway responsiveness| official statement| term treatment| mild asthma| budesonide.	JUN-2000	exercise-induced asthma| bronchial hyperresponsiveness| inhaled corticosteroids| fluticasone propionate| eosinophil cationic protein| randomized clinical trial| children|working party standardization| european respiratory society| cationic protein ecp| bronchial hyperresponsiveness| lung-function| airway responsiveness| official statement| term treatment| mild asthma| budesonide	Hofstra, WB; Neijens, HJ; Duiverman, EJ; Kouwenberg, JM; Mulder, PGH; Kuethe, MC; Sterk, PJ	Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma		PEDIATRIC PULMONOLOGY	exercise-induced asthma; bronchial hyperresponsiveness; inhaled corticosteroids; fluticasone propionate; eosinophil cationic protein; randomized clinical trial; children	WORKING PARTY STANDARDIZATION; EUROPEAN RESPIRATORY SOCIETY; CATIONIC PROTEIN ECP; BRONCHIAL HYPERRESPONSIVENESS; LUNG-FUNCTION; AIRWAY RESPONSIVENESS; OFFICIAL STATEMENT; TERM TREATMENT; MILD ASTHMA; BUDESONIDE	When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 mu g bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV1) greater than or equal to 70% predicted; EIB greater than or equal to 20% fall in FEV1 from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were rerandomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV1 from baseline) and methacholine challenge using a dosimetric technique (expressed as PD20) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV1 being reduced from 34.1% to 9.9% for 100 mu g FP bid, and from 35.9% to 7.6% for 250 mu g FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD20 methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 mu g FP bid, 1.6 dose steps; 250 mu g FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment. (C) 2000 Wiley-Liss, Inc.	41	81	2000	9	10.1002/(SICI)1099-0496(200006)29:6<415::AID-PPUL1>3.0.CO;2-7	Pediatrics; Respiratory System
Plastic wall materials in the home and respiratory health in young children. Objectives, The relation between the presence of plastic wall materials in the home and respiratory health in children was assessed. Methods. This population-based cross-sectional study involved 2568 Finnish children aged 1 to 7 years. Results. In logistic regression models, lower respiratory tract symptoms-persistent wheezing (adjusted odds ratio [OR] = 3.42, 95% confidence interval [CI] = 1.13, 10.36), cough (OR=2.41, 95% CI = 1.04, 5.63), and phlegm (OR= 2.76, 95% Cf = 1.03, 7.41)-were strongly related to the presence of plastic wall materials, whereas upper respiratory symptoms were not. The risk of asthma (OR = 1.52, 95% CI = 0.35, 6.71) and pneumonia (OR= 1.81, 95% CI = 0.62, 5.29) was also increased in children exposed to such materials. Conclusions. Emissions from plastic materials indoors may have adverse effects on the lower respiratory tracts of small children.. bronchial obstruction| symptoms| asthma.	MAY-2000	bronchial obstruction| symptoms| asthma	Jaakkola, JJK; Verkasalo, PK; Jaakkola, N	Plastic wall materials in the home and respiratory health in young children		AMERICAN JOURNAL OF PUBLIC HEALTH		BRONCHIAL OBSTRUCTION; SYMPTOMS; ASTHMA	Objectives, The relation between the presence of plastic wall materials in the home and respiratory health in children was assessed. Methods. This population-based cross-sectional study involved 2568 Finnish children aged 1 to 7 years. Results. In logistic regression models, lower respiratory tract symptoms-persistent wheezing (adjusted odds ratio [OR] = 3.42, 95% confidence interval [CI] = 1.13, 10.36), cough (OR=2.41, 95% CI = 1.04, 5.63), and phlegm (OR= 2.76, 95% Cf = 1.03, 7.41)-were strongly related to the presence of plastic wall materials, whereas upper respiratory symptoms were not. The risk of asthma (OR = 1.52, 95% CI = 0.35, 6.71) and pneumonia (OR= 1.81, 95% CI = 0.62, 5.29) was also increased in children exposed to such materials. Conclusions. Emissions from plastic materials indoors may have adverse effects on the lower respiratory tracts of small children.	7	81	2000	3	10.2105/AJPH.90.5.797	Public, Environmental & Occupational Health
Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung. Asthma pathogenesis is focused around conducting airways. The reasons for this focus have been unclear because it has not been possible to track the sites and timing of antigen uptake or subsequent antigen presentation to effector T cells. In this study, we use two-photon microscopy of the lung parenchyma and note accumulation of CD11b(+) dendritic cells (DCs) around the airway after allergen challenge but very limited access of these airway-adjacent DCs to the contents of the airspace. In contrast, we observed prevalent transepithelial uptake of particulate antigens by alveolar DCs. These distinct sites are temporally linked, as early antigen uptake in alveoli gives rise to DC and antigen retention in the airway-adjacent region. Antigen-specific T cells also accumulate in the airway-adjacent region after allergen challenge and are activated by the accumulated DCs. Thus, we propose that later airway hyperreactivity results from selective retention of allergen-presenting DCs and antigen-specific T cells in airway-adjacent interaction zones, not from variation in the abilities of individual DCs to survey the lung.. tight junction proteins| dust mite allergen| in-vivo| immune-system| lymph-node| 2-photon microscopy| respiratory-tract| chronic asthma| atopic asthma| mouse.	JUN 4-2012	tight junction proteins| dust mite allergen| in-vivo| immune-system| lymph-node| 2-photon microscopy| respiratory-tract| chronic asthma| atopic asthma| mouse	Thornton, EE; Looney, MR; Bose, O; Sen, D; Sheppard, D; Locksley, R; Huang, XZ; Krummel, MF	Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung		JOURNAL OF EXPERIMENTAL MEDICINE		TIGHT JUNCTION PROTEINS; DUST MITE ALLERGEN; IN-VIVO; IMMUNE-SYSTEM; LYMPH-NODE; 2-PHOTON MICROSCOPY; RESPIRATORY-TRACT; CHRONIC ASTHMA; ATOPIC ASTHMA; MOUSE	Asthma pathogenesis is focused around conducting airways. The reasons for this focus have been unclear because it has not been possible to track the sites and timing of antigen uptake or subsequent antigen presentation to effector T cells. In this study, we use two-photon microscopy of the lung parenchyma and note accumulation of CD11b(+) dendritic cells (DCs) around the airway after allergen challenge but very limited access of these airway-adjacent DCs to the contents of the airspace. In contrast, we observed prevalent transepithelial uptake of particulate antigens by alveolar DCs. These distinct sites are temporally linked, as early antigen uptake in alveoli gives rise to DC and antigen retention in the airway-adjacent region. Antigen-specific T cells also accumulate in the airway-adjacent region after allergen challenge and are activated by the accumulated DCs. Thus, we propose that later airway hyperreactivity results from selective retention of allergen-presenting DCs and antigen-specific T cells in airway-adjacent interaction zones, not from variation in the abilities of individual DCs to survey the lung.	54	80	2012	17	10.1084/jem.20112667	Immunology; Research & Experimental Medicine
Mechanisms of immunotherapy to aeroallergens. Allergen immunotherapy is allergen-specific, allergen dose-and time-dependent and is associated with long-term clinical and immunological tolerance that persists for years after discontinuation. Successful immunotherapy is accompanied by the suppression of numbers of T-helper 2 (Th2) effector cells, eosinophils, basophils, c-kit + mast cells and neutrophils infiltration in target organs, induction of IL-10 and/or TGF-beta + Treg cells and increases in 'protective' non-inflammatory blocking antibodies, particularly IgG4 and IgA2 subclasses with inhibitory activity. These events are accompanied by a reduction and/or a redirection of underlying antigen-specific Th2-type T cell-driven hypersensitivity to the allergen(s) used for therapy. This suppression occurs within weeks or months as a consequence of the appearance of a population of regulatory T cells that exert their effects by mechanisms involving cell-cell contact, but also by the release of cytokines such as IL-10 (increases IgG4) and TGF-beta (increases specific IgA). The more delayed-in-time appearance of antigen-specific T-helper 1 responses and alternative mechanisms such as Th2 cell anergy and/or apoptosis may also be involved. The mechanisms of sublingual immunotherapy are similar to those following a subcutaneous administration of allergen, whereas it is likely that additional events following antigen presentation in the sublingual mucosa and regional lymph nodes are involved. These insights have resulted in novel approaches and portend future biomarkers that may be surrogate or predictive of the clinical response to treatment.. grass-pollen immunotherapy| randomized controlled-trial| regulatory t-cells| fc-epsilon-ri| seasonal allergic rhinoconjunctivitis| messenger-rna expression| house-dust mites| lymphocytic activation molecule| systemic immunological changes| basophil histamine-release.	SEP-2011	grass-pollen immunotherapy| randomized controlled-trial| regulatory t-cells| fc-epsilon-ri| seasonal allergic rhinoconjunctivitis| messenger-rna expression| house-dust mites| lymphocytic activation molecule| systemic immunological changes| basophil histamine-release	Shamji, MH; Durham, SR	Mechanisms of immunotherapy to aeroallergens		CLINICAL AND EXPERIMENTAL ALLERGY		GRASS-POLLEN IMMUNOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; REGULATORY T-CELLS; FC-EPSILON-RI; SEASONAL ALLERGIC RHINOCONJUNCTIVITIS; MESSENGER-RNA EXPRESSION; HOUSE-DUST MITES; LYMPHOCYTIC ACTIVATION MOLECULE; SYSTEMIC IMMUNOLOGICAL CHANGES; BASOPHIL HISTAMINE-RELEASE	Allergen immunotherapy is allergen-specific, allergen dose-and time-dependent and is associated with long-term clinical and immunological tolerance that persists for years after discontinuation. Successful immunotherapy is accompanied by the suppression of numbers of T-helper 2 (Th2) effector cells, eosinophils, basophils, c-kit + mast cells and neutrophils infiltration in target organs, induction of IL-10 and/or TGF-beta + Treg cells and increases in 'protective' non-inflammatory blocking antibodies, particularly IgG4 and IgA2 subclasses with inhibitory activity. These events are accompanied by a reduction and/or a redirection of underlying antigen-specific Th2-type T cell-driven hypersensitivity to the allergen(s) used for therapy. This suppression occurs within weeks or months as a consequence of the appearance of a population of regulatory T cells that exert their effects by mechanisms involving cell-cell contact, but also by the release of cytokines such as IL-10 (increases IgG4) and TGF-beta (increases specific IgA). The more delayed-in-time appearance of antigen-specific T-helper 1 responses and alternative mechanisms such as Th2 cell anergy and/or apoptosis may also be involved. The mechanisms of sublingual immunotherapy are similar to those following a subcutaneous administration of allergen, whereas it is likely that additional events following antigen presentation in the sublingual mucosa and regional lymph nodes are involved. These insights have resulted in novel approaches and portend future biomarkers that may be surrogate or predictive of the clinical response to treatment.	125	80	2011	12	10.1111/j.1365-2222.2011.03804.x	Allergy; Immunology
Formaldehyde Exposure and Asthma in Children: A Systematic Review. OBJECTIVE: Despite multiple published studies regarding the association between formaldehyde exposure and childhood asthma, a consistent association has not been identified. Here we report the results of a systematic review of published literature in order to provide a more comprehensive picture of this relationship. DATA SOURCES: After a comprehensive literature search, we identified seven peer-reviewed studies providing quantitative results regarding the association between formaldehyde exposure and asthma in children. Studies were heterogeneous with respect to the definition of asthma (e.g., self-report, physician diagnosis). Most of the studies were cross-sectional. DATA EXTRACTION: For each study, an odds ratio (OR) and 95% confidence interval (CI) for asthma were either abstracted from published results or calculated based on the data provided. Characteristics regarding the study design and population were also abstracted. DATA SYNTHESIS: We used fixed- and random-effects models to calculate pooled ORs and 95% Cls; measures of heterogeneity were also calculated. A fixed-effects model produced an OR of 1.03 (95% Cl, 1.02-1.04), and random effects model produced an OR of 1.17 (95% Cl, 1.01-1.36), both reflecting an increase of 10 mu g/m(3) of formaldehyde. Both the Q and I(2) statistics indicated a moderate amount of heterogeneity. CONCLUSIONS: Results indicate a significant positive association between formaldehyde exposure and childhood asthma. Given the largely cross-sectional nature of the studies underlying this meta-analysis, further well-designed prospective epidemiologic studies are needed.. asthma| children| epidemiology| formaldehyde| meta-analysis|volatile organic-compounds| risk-factors| school environment| air-pollutants| united-states| indoor| symptoms| schoolchildren| sensitization| allergy.	MAR-2010	asthma| children| epidemiology| formaldehyde| meta-analysis|volatile organic-compounds| risk-factors| school environment| air-pollutants| united-states| indoor| symptoms| schoolchildren| sensitization| allergy	McGwin, G; Lienert, J; Kennedy, JI	Formaldehyde Exposure and Asthma in Children: A Systematic Review		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; children; epidemiology; formaldehyde; meta-analysis	VOLATILE ORGANIC-COMPOUNDS; RISK-FACTORS; SCHOOL ENVIRONMENT; AIR-POLLUTANTS; UNITED-STATES; INDOOR; SYMPTOMS; SCHOOLCHILDREN; SENSITIZATION; ALLERGY	OBJECTIVE: Despite multiple published studies regarding the association between formaldehyde exposure and childhood asthma, a consistent association has not been identified. Here we report the results of a systematic review of published literature in order to provide a more comprehensive picture of this relationship. DATA SOURCES: After a comprehensive literature search, we identified seven peer-reviewed studies providing quantitative results regarding the association between formaldehyde exposure and asthma in children. Studies were heterogeneous with respect to the definition of asthma (e.g., self-report, physician diagnosis). Most of the studies were cross-sectional. DATA EXTRACTION: For each study, an odds ratio (OR) and 95% confidence interval (CI) for asthma were either abstracted from published results or calculated based on the data provided. Characteristics regarding the study design and population were also abstracted. DATA SYNTHESIS: We used fixed- and random-effects models to calculate pooled ORs and 95% Cls; measures of heterogeneity were also calculated. A fixed-effects model produced an OR of 1.03 (95% Cl, 1.02-1.04), and random effects model produced an OR of 1.17 (95% Cl, 1.01-1.36), both reflecting an increase of 10 mu g/m(3) of formaldehyde. Both the Q and I(2) statistics indicated a moderate amount of heterogeneity. CONCLUSIONS: Results indicate a significant positive association between formaldehyde exposure and childhood asthma. Given the largely cross-sectional nature of the studies underlying this meta-analysis, further well-designed prospective epidemiologic studies are needed.	29	80	2010	5	10.1289/ehp.0901143	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
The innate immune response to Aspergillus fumigatus. Despite the development of new treatments, the mortality due to invasive pulmonary aspergillosis remains above 50%, reaching 95% in certain situations. The battle against Aspergillus fumigatus involves several components of the pulmonary innate immune system: cells, mediators, and natural antifungal molecules involved in the recognition and elimination of the fungus, thereby preventing colonization of the respiratory system. With the 10,000-15,000 1 of air we inhale each day, the lungs are constantly exposed to a wide range of microorganisms, such as A. fumigatus. This fungus is ubiquitous in the environment and can release large numbers of spores able, due to their small size, to penetrate the respiratory tract. The spores of A. fumigatus, like any other pathogen, are then confronted with the innate immune system, a constitutive defense system that is permanently active and tightly regulated. The various elements of the pulmonary innate immune system-physical and cellular barriers and soluble mediators-are involved in the recognition and elimination of pathogens, thereby preventing colonization of the respiratory system. Consequently, the presence of spores in immunocompetent hosts is completely innocuous, because these spores are normally eliminated. However, changes in one of the components of the defense system may lead to the development of pulmonary infections. Thus, in immunocompromised individuals, the spores are able to develop and cause pulmonary mycoses. These mycoses, known as aspergillosis, are highly variable, with the range of presentations extending from an allergy-type illness, allergic bronchopulmonary aspergilloses, to a very serious generalized and frequently fatal infection: invasive pulmonary aspergillosis (IPA). (C) 2009 Elsevier Masson SAS. All rights reserved.. aspergillus fumigatus| innate defense| lung| infection|invasive pulmonary aspergillosis| colony-stimulating factor| toll-like receptors| host-defense| in-vitro| antifungal activity| candida-albicans| binding lectin| systemic aspergillosis| immunosuppressed mice.	OCT-2009	aspergillus fumigatus| innate defense| lung| infection|invasive pulmonary aspergillosis| colony-stimulating factor| toll-like receptors| host-defense| in-vitro| antifungal activity| candida-albicans| binding lectin| systemic aspergillosis| immunosuppressed mice	Balloy, V; Chignard, M	The innate immune response to Aspergillus fumigatus		MICROBES AND INFECTION	Aspergillus fumigatus; Innate defense; Lung; Infection	INVASIVE PULMONARY ASPERGILLOSIS; COLONY-STIMULATING FACTOR; TOLL-LIKE RECEPTORS; HOST-DEFENSE; IN-VITRO; ANTIFUNGAL ACTIVITY; CANDIDA-ALBICANS; BINDING LECTIN; SYSTEMIC ASPERGILLOSIS; IMMUNOSUPPRESSED MICE	Despite the development of new treatments, the mortality due to invasive pulmonary aspergillosis remains above 50%, reaching 95% in certain situations. The battle against Aspergillus fumigatus involves several components of the pulmonary innate immune system: cells, mediators, and natural antifungal molecules involved in the recognition and elimination of the fungus, thereby preventing colonization of the respiratory system. With the 10,000-15,000 1 of air we inhale each day, the lungs are constantly exposed to a wide range of microorganisms, such as A. fumigatus. This fungus is ubiquitous in the environment and can release large numbers of spores able, due to their small size, to penetrate the respiratory tract. The spores of A. fumigatus, like any other pathogen, are then confronted with the innate immune system, a constitutive defense system that is permanently active and tightly regulated. The various elements of the pulmonary innate immune system-physical and cellular barriers and soluble mediators-are involved in the recognition and elimination of pathogens, thereby preventing colonization of the respiratory system. Consequently, the presence of spores in immunocompetent hosts is completely innocuous, because these spores are normally eliminated. However, changes in one of the components of the defense system may lead to the development of pulmonary infections. Thus, in immunocompromised individuals, the spores are able to develop and cause pulmonary mycoses. These mycoses, known as aspergillosis, are highly variable, with the range of presentations extending from an allergy-type illness, allergic bronchopulmonary aspergilloses, to a very serious generalized and frequently fatal infection: invasive pulmonary aspergillosis (IPA). (C) 2009 Elsevier Masson SAS. All rights reserved.	64	80	2009	9	10.1016/j.micinf.2009.07.002	Immunology; Infectious Diseases; Microbiology
Childhood asthma may be a consequence of vitamin D deficiency. Purpose of review Vitamin D deficiency has been rediscovered as a public-health problem worldwide. It has been postulated that vitamin D deficiency may explain a portion of the asthma epidemic. The purpose of this review is to present the evidence for a role of vitamin D in asthma. Recent findings Both animal models and studies in human fetal tissues show that vitamin D plays a role in fetal lung growth and maturation. Epidemiologic studies have also suggested that higher prenatal vitamin D intakes have a protective role against wheezing illnesses in young children. Vitamin D may protect against wheezing illnesses through its role in upregulating antimicrobial proteins or through its multiple immune effects. In addition, vitamin D may play a therapeutic role in steroid resistant asthmatics, and lower vitamin D levels have recently been associated with higher risks for asthma exacerbations. Summary Improving vitamin D status holds promise in primary prevention of asthma, in decreasing exacerbations of disease, and in treating steroid resistance. However, the appropriate level of circulating vitamin D for optimal immune functioning remains unclear. Because vitamin D deficiency is prevalent even in sun-replete areas, clinical trials are needed to definitively answer questions about the role of vitamin D in asthma.. allergies| asthma| sun exposure| vitamin d| wheeze|regulatory t-cells| nutrition examination survey| imr-90 human fibroblasts| 3rd national-health| smooth-muscle-cells| rat lung explants| d-receptor gene| 1,25-dihydroxyvitamin d-3| 1-alpha,25-dihydroxyvitamin d-3| 25-hydroxyvitamin d.	JUN-2009	allergies| asthma| sun exposure| vitamin d| wheeze|regulatory t-cells| nutrition examination survey| imr-90 human fibroblasts| 3rd national-health| smooth-muscle-cells| rat lung explants| d-receptor gene| 1,25-dihydroxyvitamin d-3| 1-alpha,25-dihydroxyvitamin d-3| 25-hydroxyvitamin d	Litonjua, AA	Childhood asthma may be a consequence of vitamin D deficiency		CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY	allergies; asthma; sun exposure; vitamin D; wheeze	REGULATORY T-CELLS; NUTRITION EXAMINATION SURVEY; IMR-90 HUMAN FIBROBLASTS; 3RD NATIONAL-HEALTH; SMOOTH-MUSCLE-CELLS; RAT LUNG EXPLANTS; D-RECEPTOR GENE; 1,25-DIHYDROXYVITAMIN D-3; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; 25-HYDROXYVITAMIN D	Purpose of review Vitamin D deficiency has been rediscovered as a public-health problem worldwide. It has been postulated that vitamin D deficiency may explain a portion of the asthma epidemic. The purpose of this review is to present the evidence for a role of vitamin D in asthma. Recent findings Both animal models and studies in human fetal tissues show that vitamin D plays a role in fetal lung growth and maturation. Epidemiologic studies have also suggested that higher prenatal vitamin D intakes have a protective role against wheezing illnesses in young children. Vitamin D may protect against wheezing illnesses through its role in upregulating antimicrobial proteins or through its multiple immune effects. In addition, vitamin D may play a therapeutic role in steroid resistant asthmatics, and lower vitamin D levels have recently been associated with higher risks for asthma exacerbations. Summary Improving vitamin D status holds promise in primary prevention of asthma, in decreasing exacerbations of disease, and in treating steroid resistance. However, the appropriate level of circulating vitamin D for optimal immune functioning remains unclear. Because vitamin D deficiency is prevalent even in sun-replete areas, clinical trials are needed to definitively answer questions about the role of vitamin D in asthma.	87	80	2009	6	10.1097/ACI.0b013e32832b36cd	Allergy; Immunology
T regulatory cells and their counterparts: masters of immune regulation. The interaction of environmental and genetic factors with the immune system can lead to the development of allergic diseases. The essential step in this progress is the generation of allergen-specific CD4(+) T-helper (Th) type 2 cells that mediate several effector functions. The influence of Th2 cytokines leads to the production of allergen-specific IgE antibodies by B cells, development and recruitment of eosinophils, mucus production and bronchial hyperreactivity, as well as tissue homing of other Th2 cells and eosinophils. Meanwhile, Th1 cells may contribute to chronicity and the effector phases. T cells termed T regulatory (Treg) cells, which have immunosuppressive functions and cytokine profiles distinct from that of either Th1 or Th2 cells, have been intensely investigated during the last 13 years. Treg cell response is characterized by an abolished allergen-specific T cell proliferation and the suppressed secretion of Th1 and Th2-type cytokines. Treg cells are able to inhibit the development of allergen-specific Th2 and Th1 cell responses and therefore play an important role in a healthy immune response to allergens. In addition, Treg cells potently suppress IgE production and directly or indirectly suppress the activity of effector cells of allergic inflammation, such as eosinophils, basophils and mast cells. Currently, Treg cells represent an exciting area of research, where understanding the mechanisms of peripheral tolerance to allergens may soon lead to more rational and safer approaches for the prevention and cure of allergic diseases.. growth-factor-beta| immunological self-tolerance| allergen-specific immunotherapy| transcription factor foxp3| late asthmatic reactions| bee venom immunotherapy| dendritic cells| in-vivo| nk cells| cutting edge.	MAY-2009	growth-factor-beta| immunological self-tolerance| allergen-specific immunotherapy| transcription factor foxp3| late asthmatic reactions| bee venom immunotherapy| dendritic cells| in-vivo| nk cells| cutting edge	Ozdemir, C; Akdis, M; Akdis, CA	T regulatory cells and their counterparts: masters of immune regulation		CLINICAL AND EXPERIMENTAL ALLERGY		GROWTH-FACTOR-BETA; IMMUNOLOGICAL SELF-TOLERANCE; ALLERGEN-SPECIFIC IMMUNOTHERAPY; TRANSCRIPTION FACTOR FOXP3; LATE ASTHMATIC REACTIONS; BEE VENOM IMMUNOTHERAPY; DENDRITIC CELLS; IN-VIVO; NK CELLS; CUTTING EDGE	The interaction of environmental and genetic factors with the immune system can lead to the development of allergic diseases. The essential step in this progress is the generation of allergen-specific CD4(+) T-helper (Th) type 2 cells that mediate several effector functions. The influence of Th2 cytokines leads to the production of allergen-specific IgE antibodies by B cells, development and recruitment of eosinophils, mucus production and bronchial hyperreactivity, as well as tissue homing of other Th2 cells and eosinophils. Meanwhile, Th1 cells may contribute to chronicity and the effector phases. T cells termed T regulatory (Treg) cells, which have immunosuppressive functions and cytokine profiles distinct from that of either Th1 or Th2 cells, have been intensely investigated during the last 13 years. Treg cell response is characterized by an abolished allergen-specific T cell proliferation and the suppressed secretion of Th1 and Th2-type cytokines. Treg cells are able to inhibit the development of allergen-specific Th2 and Th1 cell responses and therefore play an important role in a healthy immune response to allergens. In addition, Treg cells potently suppress IgE production and directly or indirectly suppress the activity of effector cells of allergic inflammation, such as eosinophils, basophils and mast cells. Currently, Treg cells represent an exciting area of research, where understanding the mechanisms of peripheral tolerance to allergens may soon lead to more rational and safer approaches for the prevention and cure of allergic diseases.	155	80	2009	14	10.1111/j.1365-2222.2009.03242.x	Allergy; Immunology
Glutathione-S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children. Background: Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesised that glutathione-S-transferase (GST) P1, GSTM1, exercise and ozone exposure have interrelated effects on the pathogenesis of asthma. Methods: Associations of the well characterised null variant of GSTM1 and four single nucleotide polymorphisms (SNPs) that characterised common variation in the GSTP1 locus with new onset asthma in a cohort of 1610 school children were examined. Children's exercise and ozone exposure were classified using participation in team sports and community annual average ozone levels, respectively. Results: A two SNP model involving putatively functional variants (rs6591255, rs1695 (Ile105Va)) best captured the association between GSTP1 and asthma. The risk of asthma was lower for those with the Val allele of Ile105Val (hazard ratio (HR) 0.60, 95% CI 0.4 to 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95% CI 1.1 to 1.9). The risk of asthma increased with level of exercise among ile(105) homozygotes but not among those with at least one val(105) allele (interaction p value= 0.02). The risk was highest among ile(105) homozygotes who participated in >= 3 sports in the high ozone communities (HR 6.15, 95% CI 2.2 to 7.4). GSTM1 null was independently associated with an increased risk of asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth grade cohorts recruited in 1993 and 1996. Conclusion: Children who inherit a val105 variant allele may be protected from the increased risk of asthma associated with exercise, especially in high ozone communities. GSTM1 null genotype was associated with an increased risk of asthma.. polycyclic aromatic-hydrocarbons| southern california communities| air-pollution| bronchial hyperresponsiveness| childhood asthma| risk-factors| susceptibility gene| oxidative stress| differing levels| diol epoxides.	MAR-2009	polycyclic aromatic-hydrocarbons| southern california communities| air-pollution| bronchial hyperresponsiveness| childhood asthma| risk-factors| susceptibility gene| oxidative stress| differing levels| diol epoxides	Islam, T; Berhane, K; McConnell, R; Gauderman, WJ; Avol, E; Peters, JM; Gilliland, FD	Glutathione-S-transferase (GST) P1, GSTM1, exercise, ozone and asthma incidence in school children		THORAX		POLYCYCLIC AROMATIC-HYDROCARBONS; SOUTHERN CALIFORNIA COMMUNITIES; AIR-POLLUTION; BRONCHIAL HYPERRESPONSIVENESS; CHILDHOOD ASTHMA; RISK-FACTORS; SUSCEPTIBILITY GENE; OXIDATIVE STRESS; DIFFERING LEVELS; DIOL EPOXIDES	Background: Because asthma has been associated with exercise and ozone exposure, an association likely mediated by oxidative stress, we hypothesised that glutathione-S-transferase (GST) P1, GSTM1, exercise and ozone exposure have interrelated effects on the pathogenesis of asthma. Methods: Associations of the well characterised null variant of GSTM1 and four single nucleotide polymorphisms (SNPs) that characterised common variation in the GSTP1 locus with new onset asthma in a cohort of 1610 school children were examined. Children's exercise and ozone exposure were classified using participation in team sports and community annual average ozone levels, respectively. Results: A two SNP model involving putatively functional variants (rs6591255, rs1695 (Ile105Va)) best captured the association between GSTP1 and asthma. The risk of asthma was lower for those with the Val allele of Ile105Val (hazard ratio (HR) 0.60, 95% CI 0.4 to 0.8) and higher for the variant allele of rs6591255 (HR 1.40, 95% CI 1.1 to 1.9). The risk of asthma increased with level of exercise among ile(105) homozygotes but not among those with at least one val(105) allele (interaction p value= 0.02). The risk was highest among ile(105) homozygotes who participated in >= 3 sports in the high ozone communities (HR 6.15, 95% CI 2.2 to 7.4). GSTM1 null was independently associated with an increased risk of asthma and showed little variation with air pollution or GSTP1 genotype. These results were consistent in two independent fourth grade cohorts recruited in 1993 and 1996. Conclusion: Children who inherit a val105 variant allele may be protected from the increased risk of asthma associated with exercise, especially in high ozone communities. GSTM1 null genotype was associated with an increased risk of asthma.	35	80	2009	6	10.1136/thx.2008.099366	Respiratory System
Traffic-related exposures, airway function, inflammation, and respiratory symptoms in children. Rationale: Traffic-related emissions have been associated with respiratory symptoms in some studies. However, there is limited information on how traffic-related emissions relate to lung function and airway inflammation. Objectives: To determine the differential association of traffic-related exposures with exhaled nitric oxide (NO) and lung volumes and symptoms in children with and without asthma. Methods: We performed a longitudinal study of 200 children from ages 6 to 12 years of whom half had physician-diagnosed asthma. Two-week NO(2) and 48-hour average levels of elemental carbon and particulate matter of less than 2.5 mu m (PM(2.5)) were measured at participating schools. Road and traffic densities were determine at schools and at each participant's house. Measurements and Main Results: In children with asthma, an inter-quartile increase in road density within the 50-, 100-, and 200-m home buffer areas was associated with increased exhaled NO (50 m: 28%; P = 0.03; 95% confidence interval [CI], 3-60; 100 m: 27%; P = 0.005; 95% Cl, 8-49; 200 m: 17%, P = 0.09, 95% Cl, -2 to 40), and reduced FEV(1) (50 m: -0.091 L; P = 0.038; 95% Cl, -0.174 to -0.007; 100 m: -0.072 L, P = -0.028, 95% Cl, -0.134 to -0.009; 200 in: -0.106L, P= 0.002,95%Cl, -0.171 to -0.041]). Exposure to NO(2) at schools was marginally associated with reduced FEV(1) (-0.020; P = 0.060; 95% Cl, -0.042 to 0.001). We did not observe significant associations with PM(2.5) or elemental carbon on exhaled NO. We did not observe significant reductions in lung volumes or changes in exhaled NO among healthy children. Conclusions: Vehicular traffic exposures are associated with increased levels of exhaled NO and reduced lung volumes in children with asthma.. air pollution| traffic| asthma| exhaled nitric oxide|exhaled nitric-oxide| childhood asthma| residential exposure| nitrogen-dioxide| young-children| pollution| road| health| canada| hospitalization.	DEC 15-2007	air pollution| traffic| asthma| exhaled nitric oxide|exhaled nitric-oxide| childhood asthma| residential exposure| nitrogen-dioxide| young-children| pollution| road| health| canada| hospitalization	Holguin, F; Flores, S; Ross, Z; Cortez, M; Molina, M; Molina, L; Rincon, C; Jerrett, M; Berhane, K; Granados, A; Romieu, I	Traffic-related exposures, airway function, inflammation, and respiratory symptoms in children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	air pollution; traffic; asthma; exhaled nitric oxide	EXHALED NITRIC-OXIDE; CHILDHOOD ASTHMA; RESIDENTIAL EXPOSURE; NITROGEN-DIOXIDE; YOUNG-CHILDREN; POLLUTION; ROAD; HEALTH; CANADA; HOSPITALIZATION	Rationale: Traffic-related emissions have been associated with respiratory symptoms in some studies. However, there is limited information on how traffic-related emissions relate to lung function and airway inflammation. Objectives: To determine the differential association of traffic-related exposures with exhaled nitric oxide (NO) and lung volumes and symptoms in children with and without asthma. Methods: We performed a longitudinal study of 200 children from ages 6 to 12 years of whom half had physician-diagnosed asthma. Two-week NO(2) and 48-hour average levels of elemental carbon and particulate matter of less than 2.5 mu m (PM(2.5)) were measured at participating schools. Road and traffic densities were determine at schools and at each participant's house. Measurements and Main Results: In children with asthma, an inter-quartile increase in road density within the 50-, 100-, and 200-m home buffer areas was associated with increased exhaled NO (50 m: 28%; P = 0.03; 95% confidence interval [CI], 3-60; 100 m: 27%; P = 0.005; 95% Cl, 8-49; 200 m: 17%, P = 0.09, 95% Cl, -2 to 40), and reduced FEV(1) (50 m: -0.091 L; P = 0.038; 95% Cl, -0.174 to -0.007; 100 m: -0.072 L, P = -0.028, 95% Cl, -0.134 to -0.009; 200 in: -0.106L, P= 0.002,95%Cl, -0.171 to -0.041]). Exposure to NO(2) at schools was marginally associated with reduced FEV(1) (-0.020; P = 0.060; 95% Cl, -0.042 to 0.001). We did not observe significant associations with PM(2.5) or elemental carbon on exhaled NO. We did not observe significant reductions in lung volumes or changes in exhaled NO among healthy children. Conclusions: Vehicular traffic exposures are associated with increased levels of exhaled NO and reduced lung volumes in children with asthma.	36	80	2007	7	10.1164/rccm.200611-1616OC	General & Internal Medicine; Respiratory System
Infant swimming practice, pulmonary epithelium integrity, and the risk of allergic and respiratory diseases later in childhood. Objective. Irritant gases and aerosols contaminating the air of indoor swimming pools can affect the lung epithelium and increase asthma risk in children. We evaluated the impact of infant swimming practice on allergic status and respiratory health later in childhood. Methods. Clara cell protein, surfactant-associated protein D, and total and aeroallergen-specific immunoglobulin E were measured in the serum of 341 schoolchildren aged 10 to 13 years, among whom 43 had followed an infant swimming program. Asthma was defined as doctor-diagnosed asthma and/or positive exercise-induced bronchoconstriction (15% decrease in postexercise forced expiratory volume). Results. There were no significant differences between the infant swimming group and the other children regarding the levels of exhaled nitric oxide and total or aeroallergen-specific serum immunoglobulin E. Children who swam as infants showed, by contrast, a significant decrease of serum Clara cell protein and of the serum Clara cell protein/surfactant-associated protein D ratio integrating Clara cell damage and permeability changes of the lung epithelial barrier. These effects were associated with higher risks of asthma and of recurrent bronchitis. Passive exposure to tobacco alone had no effect on these outcomes but seemed to interact with infant swimming practice to increase the risk of asthma or of recurrent bronchitis. Conclusions. Our data suggest that infant swimming practice in chlorinated indoor swimming pools is associated with airways changes that, along with other factors, seem to predispose children to the development of asthma and recurrent bronchitis.. chlorine| trichloramine| nitrogen trichloride| baby swimming| clara cell protein| cc16| childhood asthma| recurrent bronchitis|clara cell protein| exhaled nitric-oxide| pool attendance| serum pneumoproteins| asthma| lung| children| cc16| exposure| exercise.	JUN-2007	chlorine| trichloramine| nitrogen trichloride| baby swimming| clara cell protein| cc16| childhood asthma| recurrent bronchitis|clara cell protein| exhaled nitric-oxide| pool attendance| serum pneumoproteins| asthma| lung| children| cc16| exposure| exercise	Bernard, A; Carbonnelle, S; Dumont, X; Nickmilder, M	Infant swimming practice, pulmonary epithelium integrity, and the risk of allergic and respiratory diseases later in childhood		PEDIATRICS	chlorine; trichloramine; nitrogen trichloride; baby swimming; Clara cell protein; CC16; childhood asthma; recurrent bronchitis	CLARA CELL PROTEIN; EXHALED NITRIC-OXIDE; POOL ATTENDANCE; SERUM PNEUMOPROTEINS; ASTHMA; LUNG; CHILDREN; CC16; EXPOSURE; EXERCISE	Objective. Irritant gases and aerosols contaminating the air of indoor swimming pools can affect the lung epithelium and increase asthma risk in children. We evaluated the impact of infant swimming practice on allergic status and respiratory health later in childhood. Methods. Clara cell protein, surfactant-associated protein D, and total and aeroallergen-specific immunoglobulin E were measured in the serum of 341 schoolchildren aged 10 to 13 years, among whom 43 had followed an infant swimming program. Asthma was defined as doctor-diagnosed asthma and/or positive exercise-induced bronchoconstriction (15% decrease in postexercise forced expiratory volume). Results. There were no significant differences between the infant swimming group and the other children regarding the levels of exhaled nitric oxide and total or aeroallergen-specific serum immunoglobulin E. Children who swam as infants showed, by contrast, a significant decrease of serum Clara cell protein and of the serum Clara cell protein/surfactant-associated protein D ratio integrating Clara cell damage and permeability changes of the lung epithelial barrier. These effects were associated with higher risks of asthma and of recurrent bronchitis. Passive exposure to tobacco alone had no effect on these outcomes but seemed to interact with infant swimming practice to increase the risk of asthma or of recurrent bronchitis. Conclusions. Our data suggest that infant swimming practice in chlorinated indoor swimming pools is associated with airways changes that, along with other factors, seem to predispose children to the development of asthma and recurrent bronchitis.	44	80	2007	9	10.1542/peds.2006-3333	Pediatrics
Exposure to trichloramine and respiratory symptoms in indoor swimming pool workers. The association between swimming pool characteristics and activities of employees and respiratory symptoms in employees was studied. Trichloramine levels were measured to evaluate relationships with pool characteristics and to estimate long-term exposure levels. Questionnaires were available from 624 pool workers and 38 swimming facilities. Chloramine levels were measured by area sampling over 2-h periods and analysed using ion chromatography. Work-related and general respiratory symptoms, and symptoms indicatiive of atopy and bronchial hyperresponsiveness were considered. Respiratory symptom prevalence among pool workers was compared with symptoms in a Dutch population sample. Chloramine levels were modelled with regression analysis. This model was used to estimate long-term average chloramine levels for each pool studied. Employees with higher exposure reported upper respiratory symptoms with greater frequency. Upper respiratory symptoms were statistically significantly associated with cumulative chloramine levels (odds ratio (OR) >1.4 for hoarseness, lost voice, sinusitis). General respiratory symptoms were significantly elevated compared with a Dutch population sample (OR ranged 1.4-7.2). An excess risk for respiratory symptoms indicative of asthma was observed in swimming pool employees. Aggravation of existing respiratory disease or interactions between irritants and allergen exposures are the most likely explanations for the observed associations.. occupational asthma| swimming pools| trichloramines|nitrogen trichloride| asthma| chloramines| chlorine| water| air.	APR-2007	occupational asthma| swimming pools| trichloramines|nitrogen trichloride| asthma| chloramines| chlorine| water| air	Jacobs, JH; Spaan, S; van Rooy, GBGJ; Meliefste, C; Zaat, VAC; Rooyackers, JM; Heederik, D	Exposure to trichloramine and respiratory symptoms in indoor swimming pool workers		EUROPEAN RESPIRATORY JOURNAL	occupational asthma; swimming pools; trichloramines	NITROGEN TRICHLORIDE; ASTHMA; CHLORAMINES; CHLORINE; WATER; AIR	The association between swimming pool characteristics and activities of employees and respiratory symptoms in employees was studied. Trichloramine levels were measured to evaluate relationships with pool characteristics and to estimate long-term exposure levels. Questionnaires were available from 624 pool workers and 38 swimming facilities. Chloramine levels were measured by area sampling over 2-h periods and analysed using ion chromatography. Work-related and general respiratory symptoms, and symptoms indicatiive of atopy and bronchial hyperresponsiveness were considered. Respiratory symptom prevalence among pool workers was compared with symptoms in a Dutch population sample. Chloramine levels were modelled with regression analysis. This model was used to estimate long-term average chloramine levels for each pool studied. Employees with higher exposure reported upper respiratory symptoms with greater frequency. Upper respiratory symptoms were statistically significantly associated with cumulative chloramine levels (odds ratio (OR) >1.4 for hoarseness, lost voice, sinusitis). General respiratory symptoms were significantly elevated compared with a Dutch population sample (OR ranged 1.4-7.2). An excess risk for respiratory symptoms indicative of asthma was observed in swimming pool employees. Aggravation of existing respiratory disease or interactions between irritants and allergen exposures are the most likely explanations for the observed associations.	20	80	2007	9	10.1183/09031936.00024706	Respiratory System
Increased pulmonary responses to acute ozone exposure in obese db/db mice. Epidemiological studies indicate the incidence of asthma is increased in obese and overweight humans. Responses to ozone (O-3), an asthma trigger, are increased in obese (ob/ob) mice lacking the satiety hormone leptin. The long form of leptin receptor (Ob-Rb) is required for satiety; mice lacking this receptor (db/db mice) are also substantially obese. Here, wild-type (WT) and db/db mice were exposed to air or O-3 (2 ppm) for 3 h. Airway responsiveness, measured by the forced oscillation technique, was greater in db/db than WT mice after air exposure. O-3-induced increases in pulmonary resistance and airway responsiveness were also greater in db/db mice. BALF eotaxin, IL-6, KC, and MIP-2 increased 4 h after O-3 exposure and subsided by 24 h, whereas protein and neutrophils continued to increase through 24 h. For each outcome, the effect of O-3 was significantly greater in db/db than WT mice. Previously published results obtained in ob/ob mice were similar except for O-3-induced neutrophils and MIP-2, which were not different from WT mice. O-3 also induced pulmonary IL-1 beta and TNF-alpha mRNA expression in db/db but not ob/ob mice. Leptin was increased in serum of db/db mice, and pulmonary mRNA expression of short form of leptin receptor (Ob-R-a) was similar in db/db and WT mice. These data confirm obese mice have innate airway hyperresponsiveness and increased pulmonary responses to O-3. Differences between ob/ob mice, which lack leptin, and db/db mice, which lack Ob-Rb but not Ob-R-a, suggest leptin, acting through Ob-R-a, can modify some pulmonary responses to O-3.. leptin| interleukin-1 beta| airway responsiveness| macrophage inflammatory protein-2| neutrophil| ventilation|body-mass index| necrosis-factor-alpha| leptin receptor| airway hyperresponsiveness| insulin-resistance| weight-reduction| splice variants| asthma severity| tnf-alpha| in-vitro.	MAY-2006	leptin| interleukin-1 beta| airway responsiveness| macrophage inflammatory protein-2| neutrophil| ventilation|body-mass index| necrosis-factor-alpha| leptin receptor| airway hyperresponsiveness| insulin-resistance| weight-reduction| splice variants| asthma severity| tnf-alpha| in-vitro	Lu, FL; Johnston, RA; Flynt, L; Theman, TA; Terry, RD; Schwartzman, IN; Lee, A; Shore, SA	Increased pulmonary responses to acute ozone exposure in obese db/db mice		AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY	leptin; interleukin-1 beta; airway responsiveness; macrophage inflammatory protein-2; neutrophil; ventilation	BODY-MASS INDEX; NECROSIS-FACTOR-ALPHA; LEPTIN RECEPTOR; AIRWAY HYPERRESPONSIVENESS; INSULIN-RESISTANCE; WEIGHT-REDUCTION; SPLICE VARIANTS; ASTHMA SEVERITY; TNF-ALPHA; IN-VITRO	Epidemiological studies indicate the incidence of asthma is increased in obese and overweight humans. Responses to ozone (O-3), an asthma trigger, are increased in obese (ob/ob) mice lacking the satiety hormone leptin. The long form of leptin receptor (Ob-Rb) is required for satiety; mice lacking this receptor (db/db mice) are also substantially obese. Here, wild-type (WT) and db/db mice were exposed to air or O-3 (2 ppm) for 3 h. Airway responsiveness, measured by the forced oscillation technique, was greater in db/db than WT mice after air exposure. O-3-induced increases in pulmonary resistance and airway responsiveness were also greater in db/db mice. BALF eotaxin, IL-6, KC, and MIP-2 increased 4 h after O-3 exposure and subsided by 24 h, whereas protein and neutrophils continued to increase through 24 h. For each outcome, the effect of O-3 was significantly greater in db/db than WT mice. Previously published results obtained in ob/ob mice were similar except for O-3-induced neutrophils and MIP-2, which were not different from WT mice. O-3 also induced pulmonary IL-1 beta and TNF-alpha mRNA expression in db/db but not ob/ob mice. Leptin was increased in serum of db/db mice, and pulmonary mRNA expression of short form of leptin receptor (Ob-R-a) was similar in db/db and WT mice. These data confirm obese mice have innate airway hyperresponsiveness and increased pulmonary responses to O-3. Differences between ob/ob mice, which lack leptin, and db/db mice, which lack Ob-Rb but not Ob-R-a, suggest leptin, acting through Ob-R-a, can modify some pulmonary responses to O-3.	62	80	2006	10	10.1152/ajplung.00386.2005	Physiology; Respiratory System
"The effects of volatile salivary acids and bases on exhaled breath condensate pH. Rationale: Recent studies have reported acidification of exhaled breath condensate (EBC) in inflammatory lung diseases. This phenomenon, designated ""acidopnea,"" has been attributed to airway inflammation. Objectives: To determine whether salivary acids and bases can influence EBC pH in chronic obstructive pulmonary disease (COPD). Methods: Measurements were made of pH, electrolytes, and volatile bases and acids in saliva and EBC equilibrated with air in 10 healthy subjects and 10 patients. Results: The average EBC pH in COPD was reduced (normal, 7.24 +/- 0.24 SEM; range, 6.11-8.34; COPD, 6.67 +/- 0.18; range, 5.74-7.64; p = 0.079). EBCs were well buffered by NH4+/NH3 and CO2/HCO3- in all but four patients, who had NH4+ concentrations under 60 mu mol/L, and acetate concentrations that approached or exceeded those of NH4+. Saliva contained high concentrations of acetate (similar to 6,000 mu mol/L) and NH4+ (similar to 12,000 mu mol/L). EBC acetate increased and EBC NH4+ decreased when salivary pH was low, consistent with a salivary source for these volatile constituents. Nonvolatile acids did not play a significant role in determining pH of condensates because of extreme dilution of respiratory droplets by water vapor (similar to 1:12,000). Transfer of both acetic acid and NH3 from the saliva to the EBC was in the gas phase rather than droplets. bConclusions: EBC acidification in COPD can be affected by the balance of volatile salivary acids and bases, suggesting that EBC pH may not be a reliable marker of airway acidification. Salivary acidification may play an important role in acidopnea.. acetate| ammonium| bicarbonate| buffer| exhaled breath condensate|cystic-fibrosis| air-pollution| asthma| acidification| inflammation| dilution| children| ammonia| disease| cough."	FEB 15-2006	acetate| ammonium| bicarbonate| buffer| exhaled breath condensate|cystic-fibrosis| air-pollution| asthma| acidification| inflammation| dilution| children| ammonia| disease| cough	Effros, RM; Casaburi, R; Su, J; Dunning, M; Torday, J; Biller, J; Shaker, R	The effects of volatile salivary acids and bases on exhaled breath condensate pH		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	acetate; ammonium; bicarbonate; buffer; exhaled breath condensate	CYSTIC-FIBROSIS; AIR-POLLUTION; ASTHMA; ACIDIFICATION; INFLAMMATION; DILUTION; CHILDREN; AMMONIA; DISEASE; COUGH	"Rationale: Recent studies have reported acidification of exhaled breath condensate (EBC) in inflammatory lung diseases. This phenomenon, designated ""acidopnea,"" has been attributed to airway inflammation. Objectives: To determine whether salivary acids and bases can influence EBC pH in chronic obstructive pulmonary disease (COPD). Methods: Measurements were made of pH, electrolytes, and volatile bases and acids in saliva and EBC equilibrated with air in 10 healthy subjects and 10 patients. Results: The average EBC pH in COPD was reduced (normal, 7.24 +/- 0.24 SEM; range, 6.11-8.34; COPD, 6.67 +/- 0.18; range, 5.74-7.64; p = 0.079). EBCs were well buffered by NH4+/NH3 and CO2/HCO3- in all but four patients, who had NH4+ concentrations under 60 mu mol/L, and acetate concentrations that approached or exceeded those of NH4+. Saliva contained high concentrations of acetate (similar to 6,000 mu mol/L) and NH4+ (similar to 12,000 mu mol/L). EBC acetate increased and EBC NH4+ decreased when salivary pH was low, consistent with a salivary source for these volatile constituents. Nonvolatile acids did not play a significant role in determining pH of condensates because of extreme dilution of respiratory droplets by water vapor (similar to 1:12,000). Transfer of both acetic acid and NH3 from the saliva to the EBC was in the gas phase rather than droplets. bConclusions: EBC acidification in COPD can be affected by the balance of volatile salivary acids and bases, suggesting that EBC pH may not be a reliable marker of airway acidification. Salivary acidification may play an important role in acidopnea."	29	80	2006	7	10.1164/rccm.200507-1059OC	General & Internal Medicine; Respiratory System
Association of indoor nitrogen dioxide exposure with respiratory symptoms in children with asthma. Rationale: Chronic exposure to indoor nitrogen dioxide (NO2) is a public health concern. Over half of U.S. households have a source of NO2, and experimental data suggest potential for adverse respiratory effects. Objective: To examine associations of indoor NO2 exposure with respiratory symptoms among children with asthma. Methods: NO2 was measured using Palmes tubes, and respiratory symptoms in the month before sampling were collected during home interviews of mothers of 728 children with active asthma. All were younger than 12 yr, lived at the sampled home for at least 2 mo, and had asthma symptoms or used maintenance medication within the previous year. Measurements: Respiratory symptoms (wheeze, persistent cough, shortness of breath, chest tightness). Results: Mean (SD) NO2 was 8.6 (9.1) ppb in homes with electric ranges and 25.9 (18.1) ppb in homes with gas stoves. In models stratified by housing type (a factor associated with socioeconomic status), gas stove presence and elevated NO2 were each significantly associated with respiratory symptoms, controlling for age, ethnicity, medication, mold/mildew, water leaks, and season of sampling. Among children in multifamily housing, exposure to gas stoves increased likelihood of wheeze (odds ratio [OR], 2.27; 95% confidence interval [95% Cl], 1.15, 4.47), shortness of breath (OR, 2.33; 95% Cl, 1.12, 5.06), and chest tightness (OR, 4.34; 95% Cl, 1.76, 10.69), whereas each 20-ppb increase in NO2 increased both likelihood of any wheeze (OR, 1.52; 95% Cl, 1.04, 2.21) or chest tightness (OR, 1.61; 95% Cl, 1.04, 2.49), and days of wheeze (rate ratio (RR), 1.33; 95% Cl, 1.05, 1.68) or chest tightness (RR, 1.51; 95% Cl, 1.18, 1.91). Conclusion: Exposure to indoor NO2 at levels well below the Environmental Protection Agency outdoor standard (53 ppb) is associated with respiratory symptoms among children with asthma in multifamily housing.. asthma| children| gas stoves| indoor environment| nitrogen dioxide| respiratory symptoms|1st year| personal exposure| preschool-children| air contaminants| gas cooking| life| no2| pollution| risk| schoolchildren.	FEB 1-2006	asthma| children| gas stoves| indoor environment| nitrogen dioxide| respiratory symptoms|1st year| personal exposure| preschool-children| air contaminants| gas cooking| life| no2| pollution| risk| schoolchildren	Belanger, K; Gent, JF; Triche, EW; Bracken, MB; Leaderer, BP	Association of indoor nitrogen dioxide exposure with respiratory symptoms in children with asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; children; gas stoves; indoor environment; nitrogen dioxide; respiratory symptoms	1ST YEAR; PERSONAL EXPOSURE; PRESCHOOL-CHILDREN; AIR CONTAMINANTS; GAS COOKING; LIFE; NO2; POLLUTION; RISK; SCHOOLCHILDREN	Rationale: Chronic exposure to indoor nitrogen dioxide (NO2) is a public health concern. Over half of U.S. households have a source of NO2, and experimental data suggest potential for adverse respiratory effects. Objective: To examine associations of indoor NO2 exposure with respiratory symptoms among children with asthma. Methods: NO2 was measured using Palmes tubes, and respiratory symptoms in the month before sampling were collected during home interviews of mothers of 728 children with active asthma. All were younger than 12 yr, lived at the sampled home for at least 2 mo, and had asthma symptoms or used maintenance medication within the previous year. Measurements: Respiratory symptoms (wheeze, persistent cough, shortness of breath, chest tightness). Results: Mean (SD) NO2 was 8.6 (9.1) ppb in homes with electric ranges and 25.9 (18.1) ppb in homes with gas stoves. In models stratified by housing type (a factor associated with socioeconomic status), gas stove presence and elevated NO2 were each significantly associated with respiratory symptoms, controlling for age, ethnicity, medication, mold/mildew, water leaks, and season of sampling. Among children in multifamily housing, exposure to gas stoves increased likelihood of wheeze (odds ratio [OR], 2.27; 95% confidence interval [95% Cl], 1.15, 4.47), shortness of breath (OR, 2.33; 95% Cl, 1.12, 5.06), and chest tightness (OR, 4.34; 95% Cl, 1.76, 10.69), whereas each 20-ppb increase in NO2 increased both likelihood of any wheeze (OR, 1.52; 95% Cl, 1.04, 2.21) or chest tightness (OR, 1.61; 95% Cl, 1.04, 2.49), and days of wheeze (rate ratio (RR), 1.33; 95% Cl, 1.05, 1.68) or chest tightness (RR, 1.51; 95% Cl, 1.18, 1.91). Conclusion: Exposure to indoor NO2 at levels well below the Environmental Protection Agency outdoor standard (53 ppb) is associated with respiratory symptoms among children with asthma in multifamily housing.	45	80	2006	7	10.1164/rccm.200408-1123OC	General & Internal Medicine; Respiratory System
Directly measured second hand smoke exposure and asthma health outcomes. Background: Because they have chronic airway inflammation, adults with asthma could have symptomatic exacerbation after exposure to second hand smoke (SHS). Surprisingly, data on the effects of SHS exposure in adults with asthma are quite limited. Most previous epidemiological studies used self-reported SHS exposure which could be biased by inaccurate reporting. In a prospective cohort study of adult nonsmokers recently admitted to hospital for asthma, the impact of SHS exposure on asthma health outcomes was examined. Methods: Recent SHS exposure during the previous 7 days was directly measured using a personal nicotine badge (n = 189) and exposure during the previous 3 months was estimated using hair nicotine and cotinine levels (n = 138). Asthma severity and health status were ascertained during telephone interviews, and subsequent admission to hospital for asthma was determined from computerised utilisation databases. Results: Most of the adults with asthma were exposed to SHS, with estimates ranging from 60% to 83% depending on the time frame and methodology. The highest level of recent SHS exposure, as measured by the personal nicotine badge, was related to greater asthma severity (mean score increment for highest tertile of nicotine level 1.56 points; 95% CI 0.18 to 2.95), controlling for sociodemographic covariates and previous smoking history. Moreover, the second and third tertiles of hair nicotine exposure during the previous month were associated with a greater baseline prospective risk of hospital admission for asthma (HR 3.73; 95% CI 1.04 to 13.30 and HR 3.61; 95% CI 1.0 to 12.9, respectively). Conclusions: Directly measured SHS exposure appears to be associated with poorer asthma outcomes. In public health terms, these results support efforts to prohibit smoking in public places.. environmental tobacco-smoke| quality-of-life| passive smoking| work disability| neonatal hair| beta-agonists| adult asthma| nicotine| risk| cotinine.	OCT-2005	environmental tobacco-smoke| quality-of-life| passive smoking| work disability| neonatal hair| beta-agonists| adult asthma| nicotine| risk| cotinine	Eisner, MD; Klein, J; Hammond, SK; Koren, G; Lactao, G; Iribarren, C	Directly measured second hand smoke exposure and asthma health outcomes		THORAX		ENVIRONMENTAL TOBACCO-SMOKE; QUALITY-OF-LIFE; PASSIVE SMOKING; WORK DISABILITY; NEONATAL HAIR; BETA-AGONISTS; ADULT ASTHMA; NICOTINE; RISK; COTININE	Background: Because they have chronic airway inflammation, adults with asthma could have symptomatic exacerbation after exposure to second hand smoke (SHS). Surprisingly, data on the effects of SHS exposure in adults with asthma are quite limited. Most previous epidemiological studies used self-reported SHS exposure which could be biased by inaccurate reporting. In a prospective cohort study of adult nonsmokers recently admitted to hospital for asthma, the impact of SHS exposure on asthma health outcomes was examined. Methods: Recent SHS exposure during the previous 7 days was directly measured using a personal nicotine badge (n = 189) and exposure during the previous 3 months was estimated using hair nicotine and cotinine levels (n = 138). Asthma severity and health status were ascertained during telephone interviews, and subsequent admission to hospital for asthma was determined from computerised utilisation databases. Results: Most of the adults with asthma were exposed to SHS, with estimates ranging from 60% to 83% depending on the time frame and methodology. The highest level of recent SHS exposure, as measured by the personal nicotine badge, was related to greater asthma severity (mean score increment for highest tertile of nicotine level 1.56 points; 95% CI 0.18 to 2.95), controlling for sociodemographic covariates and previous smoking history. Moreover, the second and third tertiles of hair nicotine exposure during the previous month were associated with a greater baseline prospective risk of hospital admission for asthma (HR 3.73; 95% CI 1.04 to 13.30 and HR 3.61; 95% CI 1.0 to 12.9, respectively). Conclusions: Directly measured SHS exposure appears to be associated with poorer asthma outcomes. In public health terms, these results support efforts to prohibit smoking in public places.	45	80	2005	8	10.1136/thx.2004.037283	Respiratory System
Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma. Rationale: Increased oxidative stress and decreased superoxide dismutase (SOD) activity in the asthmatic airway are correlated to airflow limitation and hyperreactivity. We hypothesized that asthmatic individuals with higher levels of oxidative stress may have greater loss of SOD activity, which would be reflected systemically in loss of circulating SOD activity and clinically by development of severe asthma and/or worsening airflow limitation. Methods: To investigate this, serum SOD activity and proteins, the glutathione peroxidase/glutathione antioxidant system, and oxidatively modified amino acids were measured in subjects with asthma and healthy control subjects. Results: SOD activity, but not Mn-SOD or Cu,Zn-SOD protein, was lower in asthmatic serum as compared with control, and activity loss was significantly related to airflow limitation. Further, serum SOD activity demonstrated an inverse correlation with circulating levels of 3-bromotyrosine, a posttranslational modification of proteins produced by the eosinophil peroxidase system of eosinophils. Exposure of purified Cu,Zn-SOD to physiologically relevant levels of eosinophil peroxidase-generated reactive brominating species reactive nitrogen species, or tyrosyl radicals in vitro confirmed that eosinophil-derived oxidative pathways promote enzyme inactivation. Conclusion: These findings are consistent with greater oxidant stress in asthma leading to greater inactivation of SOD, which likely amplifies inflammation and progressive airflow obstruction.. eosinophil peroxidase| in-vivo| oxidative stress| glutathione-peroxidase| antioxidant enzymes| enhanced production| tyrosine nitration| oxygen radicals| lung-diseases| mild asthma.	AUG 1-2005	eosinophil peroxidase| in-vivo| oxidative stress| glutathione-peroxidase| antioxidant enzymes| enhanced production| tyrosine nitration| oxygen radicals| lung-diseases| mild asthma	Comhair, SAA; Ricci, KS; Arroliga, M; Lara, AR; Dweik, RA; Song, W; Hazen, SL; Bleecker, ER; Busse, WW; Chung, KF; Gaston, B; Hastie, A; Hew, M; Jarjour, N; Moore, W; Peters, S; Teague, WG; Wenzel, SE; Erzurum, SC	Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		EOSINOPHIL PEROXIDASE; IN-VIVO; OXIDATIVE STRESS; GLUTATHIONE-PEROXIDASE; ANTIOXIDANT ENZYMES; ENHANCED PRODUCTION; TYROSINE NITRATION; OXYGEN RADICALS; LUNG-DISEASES; MILD ASTHMA	Rationale: Increased oxidative stress and decreased superoxide dismutase (SOD) activity in the asthmatic airway are correlated to airflow limitation and hyperreactivity. We hypothesized that asthmatic individuals with higher levels of oxidative stress may have greater loss of SOD activity, which would be reflected systemically in loss of circulating SOD activity and clinically by development of severe asthma and/or worsening airflow limitation. Methods: To investigate this, serum SOD activity and proteins, the glutathione peroxidase/glutathione antioxidant system, and oxidatively modified amino acids were measured in subjects with asthma and healthy control subjects. Results: SOD activity, but not Mn-SOD or Cu,Zn-SOD protein, was lower in asthmatic serum as compared with control, and activity loss was significantly related to airflow limitation. Further, serum SOD activity demonstrated an inverse correlation with circulating levels of 3-bromotyrosine, a posttranslational modification of proteins produced by the eosinophil peroxidase system of eosinophils. Exposure of purified Cu,Zn-SOD to physiologically relevant levels of eosinophil peroxidase-generated reactive brominating species reactive nitrogen species, or tyrosyl radicals in vitro confirmed that eosinophil-derived oxidative pathways promote enzyme inactivation. Conclusion: These findings are consistent with greater oxidant stress in asthma leading to greater inactivation of SOD, which likely amplifies inflammation and progressive airflow obstruction.	58	80	2005	8	10.1164/rccm.200502-180OC	General & Internal Medicine; Respiratory System
Fungal fragments and undocumented conidia function as new aeroallergen sources. Background: More than 100 genera of fungal conidia are currently recognized as sources of allergens. The contribution of other fungal genera plus airborne fungal hyphae and fragmented conidia to allergic diseases is poorly understood. Objective: We sought to investigate the expression of allergens from airborne wild-type fungi using the Halogen immunoassay, which uses allergic serum IgE to immunostain immobilized allergens extracted from individual fungal particles. Methods: Airborne fungi were collected onto mixed cellulose ester protein-binding membranes for 2.5 hours with volumetric air pumps. Collected fungi were incubated overnight in a humid chamber to promote the germination of conidia. The membranes were laminated with an adhesive cover slip and immunostained with an Altentaria species-sensitive serum IgE pool. The samples were examined by means of light microscopy, and positively immunostained fungal particles were classified and counted. Results: All air samples contained fungal hyphae that expressed soluble allergens and were significantly higher in concentration than counts of conidia of individual well-ebaracterized allergenic genera (P &LT; .05). Resultant immunostaining of fungal hyphae was heterogeneous, and approximately 25% of all hyphae expressed detectable allergen compared with nonstained hyphae (P &LT; .05). Fungal conidia of 10 genera that were previously uncharacterized as allergen sources were shown to demonstrate IgE binding to expressed antigens and accounted for 8% of the total airborne conidia count. Conclusions: Our analysis of wild-type fungi collected indoors presents a new paradigm of natural fungal exposure, which, in addition to commonly recognized species, implicates airborne hyphae, fragmented conidia, and the conidia of a much more diverse range of genera as airborne allergens.. allergen| alternaria species| antigen| conidia| fragment| fungal| hyphae| germination| immunoassay| mold|alternaria| asthma| germination| allergens| exposure| spores.	MAY-2005	allergen| alternaria species| antigen| conidia| fragment| fungal| hyphae| germination| immunoassay| mold|alternaria| asthma| germination| allergens| exposure| spores	Green, BJ; Sercombe, JK; Tovey, ER	Fungal fragments and undocumented conidia function as new aeroallergen sources		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen; Alternaria species; antigen; conidia; fragment; fungal; hyphae; germination; immunoassay; mold	ALTERNARIA; ASTHMA; GERMINATION; ALLERGENS; EXPOSURE; SPORES	Background: More than 100 genera of fungal conidia are currently recognized as sources of allergens. The contribution of other fungal genera plus airborne fungal hyphae and fragmented conidia to allergic diseases is poorly understood. Objective: We sought to investigate the expression of allergens from airborne wild-type fungi using the Halogen immunoassay, which uses allergic serum IgE to immunostain immobilized allergens extracted from individual fungal particles. Methods: Airborne fungi were collected onto mixed cellulose ester protein-binding membranes for 2.5 hours with volumetric air pumps. Collected fungi were incubated overnight in a humid chamber to promote the germination of conidia. The membranes were laminated with an adhesive cover slip and immunostained with an Altentaria species-sensitive serum IgE pool. The samples were examined by means of light microscopy, and positively immunostained fungal particles were classified and counted. Results: All air samples contained fungal hyphae that expressed soluble allergens and were significantly higher in concentration than counts of conidia of individual well-ebaracterized allergenic genera (P &LT; .05). Resultant immunostaining of fungal hyphae was heterogeneous, and approximately 25% of all hyphae expressed detectable allergen compared with nonstained hyphae (P &LT; .05). Fungal conidia of 10 genera that were previously uncharacterized as allergen sources were shown to demonstrate IgE binding to expressed antigens and accounted for 8% of the total airborne conidia count. Conclusions: Our analysis of wild-type fungi collected indoors presents a new paradigm of natural fungal exposure, which, in addition to commonly recognized species, implicates airborne hyphae, fragmented conidia, and the conidia of a much more diverse range of genera as airborne allergens.	17	80	2005	6	10.1016/j.jaci.2005.02.009	Allergy; Immunology
Respiratory morbidity 20 years after RSV infection in infancy. Epidemiological data suggest that respiratory syncytial virus (RSV) infection in early life is a risk factor for later asthma. There are no prospective studies on RSV infection starting from infancy progressing through childhood into adulthood. We followed up a cohort of children, hospitalized for RSV bronchiolitis or RSV pneumonia before age 24 months, until age 18-20 years. The aim of the study was to evaluate early RSV infection as a risk factor for asthma, bronchial reactivity, and lung function abnormalities in young adults. The participants filled in a questionnaire on asthma and asthma-like symptoms. The clinical study included flow-volume spirometry (FVS), methacholine inhalation challenge (MIC), home PEF (peak expiratory flow) monitoring, and skin prick tests (SPT) to common allergens. Asthma was present in 17-22% of 36 index subjects, depending on asthma definition, compared to 11% of 45 controls. Furthermore, FEV% and MEF25 were lower, and MEF50 tended to be lower, in index than in control subjects. One or more abnormal lung function results were found in 16 (44%) index subjects, but only in 5 (11%) controls (P < 0.01). Bronchial reactivity (PD20 <4,900 mug methacholine) was demonstrated in 16 (46%) index subjects and 14 (32%) controls (NS). At least one positive SPT result was present in 21 (60%) index subjects; 6 (29%) had asthma (NS vs. nonatopic index subjects); 13 (62%) had abnormal lung function (P < 0.05); and 14 (67%) had bronchial reactivity (P < 0.01). In the logistic regression adjusted for atopy, as defined by SPT positivity, RSV infection in infancy was an independent risk factor for lung function abnormality (one or more abnormal results in FVS; OR, 5.27; 95% Cl, 1.6017.36), and also for decreased FEV% and MEF50 when these were analyzed separately. However, RSV infection in infancy was not a significant risk factor for asthma or bronchial reactivity. In young adults, lung function abnormalities may be associated with RSV infection which required hospitalization in infancy. (C) 2004 Wiley-Liss, Inc.. respiratory syncytial virus| bronchiolitis| pneumonia| lung function| asthma| atopy| childhood| adulthood|syncytial virus bronchiolitis| bronchial-asthma| age| childhood| children| allergy| history| illness| atopy| risk.	AUG-2004	respiratory syncytial virus| bronchiolitis| pneumonia| lung function| asthma| atopy| childhood| adulthood|syncytial virus bronchiolitis| bronchial-asthma| age| childhood| children| allergy| history| illness| atopy| risk	Korppi, M; Piippo-Savolainen, E; Korhonen, K; Remes, S	Respiratory morbidity 20 years after RSV infection in infancy		PEDIATRIC PULMONOLOGY	respiratory syncytial virus; bronchiolitis; pneumonia; lung function; asthma; atopy; childhood; adulthood	SYNCYTIAL VIRUS BRONCHIOLITIS; BRONCHIAL-ASTHMA; AGE; CHILDHOOD; CHILDREN; ALLERGY; HISTORY; ILLNESS; ATOPY; RISK	Epidemiological data suggest that respiratory syncytial virus (RSV) infection in early life is a risk factor for later asthma. There are no prospective studies on RSV infection starting from infancy progressing through childhood into adulthood. We followed up a cohort of children, hospitalized for RSV bronchiolitis or RSV pneumonia before age 24 months, until age 18-20 years. The aim of the study was to evaluate early RSV infection as a risk factor for asthma, bronchial reactivity, and lung function abnormalities in young adults. The participants filled in a questionnaire on asthma and asthma-like symptoms. The clinical study included flow-volume spirometry (FVS), methacholine inhalation challenge (MIC), home PEF (peak expiratory flow) monitoring, and skin prick tests (SPT) to common allergens. Asthma was present in 17-22% of 36 index subjects, depending on asthma definition, compared to 11% of 45 controls. Furthermore, FEV% and MEF25 were lower, and MEF50 tended to be lower, in index than in control subjects. One or more abnormal lung function results were found in 16 (44%) index subjects, but only in 5 (11%) controls (P < 0.01). Bronchial reactivity (PD20 <4,900 mug methacholine) was demonstrated in 16 (46%) index subjects and 14 (32%) controls (NS). At least one positive SPT result was present in 21 (60%) index subjects; 6 (29%) had asthma (NS vs. nonatopic index subjects); 13 (62%) had abnormal lung function (P < 0.05); and 14 (67%) had bronchial reactivity (P < 0.01). In the logistic regression adjusted for atopy, as defined by SPT positivity, RSV infection in infancy was an independent risk factor for lung function abnormality (one or more abnormal results in FVS; OR, 5.27; 95% Cl, 1.6017.36), and also for decreased FEV% and MEF50 when these were analyzed separately. However, RSV infection in infancy was not a significant risk factor for asthma or bronchial reactivity. In young adults, lung function abnormalities may be associated with RSV infection which required hospitalization in infancy. (C) 2004 Wiley-Liss, Inc.	28	80	2004	6	10.1002/ppul.20058	Pediatrics; Respiratory System
Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema. It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30-42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0-6 months and 30-42 months, respectively (n=2,044), and with eczema at 18-30 months (n=2,173), were analysed. Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy. The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.. birth cohort| eczema| prenatal/foetal nutrition| trace elements/minerals| wheezing|cytokine production| atopic-dermatitis| iron-deficiency| immune function| fetal-growth| disease| birth| children| asthma| pregnancy.	AUG-2004	birth cohort| eczema| prenatal/foetal nutrition| trace elements/minerals| wheezing|cytokine production| atopic-dermatitis| iron-deficiency| immune function| fetal-growth| disease| birth| children| asthma| pregnancy	Shaheen, SO; Newson, RB; Henderson, AJ; Emmett, PM; Sherriff, A; Cooke, M	Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema		EUROPEAN RESPIRATORY JOURNAL	birth cohort; eczema; prenatal/foetal nutrition; trace elements/minerals; wheezing	CYTOKINE PRODUCTION; ATOPIC-DERMATITIS; IRON-DEFICIENCY; IMMUNE FUNCTION; FETAL-GROWTH; DISEASE; BIRTH; CHILDREN; ASTHMA; PREGNANCY	It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30-42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0-6 months and 30-42 months, respectively (n=2,044), and with eczema at 18-30 months (n=2,173), were analysed. Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy. The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.	40	80	2004	6	10.1183/09031936.04.00117803	Respiratory System
MD-2: the Toll 'gatekeeper' in endotoxin signalling. Lipopolysaccharide (LPS) from the outer cell wall of Gram-negative bacteria is a potent stimulator of the mammalian innate immune system. The Toll-like receptor 4 (TLR4) pathway triggers the inflammatory responses induced by LPS in a process that requires the interaction of LPS-bound myeloid differentiation-2 (MD-2) with TLR4. Here we propose two possible mechanisms for LPS recognition and signalling that take into account both the structural information available for TLR4 and MD-2, and the determinants of endotoxicity, namely, the acylation and phosphorylation patterns of LIPS. In our first model, LPS induces the association of two TLR4-MD-2 heterodimers by binding to two different molecules of MD-2 through the acyl chains of lipid A. In our second model, the binding of LPS to a single TLR4-MD-2 complex facilitates the recruitment of a second TLR4-MD-2 heterodimer. These models contrast with the activation of Drosophila Toll, where the receptor is crosslinked by a dimeric protein ligand.. dust-mite allergen| confers lipopolysaccharide responsiveness| n-linked glycosylations| lps binding-protein| crystal-structure| drosophila toll| gm2-activator protein| angstrom resolution| escherichia-coli| innate immunity.	JUN-2004	dust-mite allergen| confers lipopolysaccharide responsiveness| n-linked glycosylations| lps binding-protein| crystal-structure| drosophila toll| gm2-activator protein| angstrom resolution| escherichia-coli| innate immunity	Gangloff, M; Gay, NJ	MD-2: the Toll 'gatekeeper' in endotoxin signalling		TRENDS IN BIOCHEMICAL SCIENCES		DUST-MITE ALLERGEN; CONFERS LIPOPOLYSACCHARIDE RESPONSIVENESS; N-LINKED GLYCOSYLATIONS; LPS BINDING-PROTEIN; CRYSTAL-STRUCTURE; DROSOPHILA TOLL; GM2-ACTIVATOR PROTEIN; ANGSTROM RESOLUTION; ESCHERICHIA-COLI; INNATE IMMUNITY	Lipopolysaccharide (LPS) from the outer cell wall of Gram-negative bacteria is a potent stimulator of the mammalian innate immune system. The Toll-like receptor 4 (TLR4) pathway triggers the inflammatory responses induced by LPS in a process that requires the interaction of LPS-bound myeloid differentiation-2 (MD-2) with TLR4. Here we propose two possible mechanisms for LPS recognition and signalling that take into account both the structural information available for TLR4 and MD-2, and the determinants of endotoxicity, namely, the acylation and phosphorylation patterns of LIPS. In our first model, LPS induces the association of two TLR4-MD-2 heterodimers by binding to two different molecules of MD-2 through the acyl chains of lipid A. In our second model, the binding of LPS to a single TLR4-MD-2 complex facilitates the recruitment of a second TLR4-MD-2 heterodimer. These models contrast with the activation of Drosophila Toll, where the receptor is crosslinked by a dimeric protein ligand.	52	80	2004	7	10.1016/j.tibs.2004.04.008	Biochemistry & Molecular Biology
Serum vitamin levels and the risk of asthma in children. Dietary intake, especially of antioxidant vitamins A, C, E, and the carotenoids, has been linked with the presence and severity of asthma. From the Third National Health and Nutrition Examination Survey (NHANES III), conducted in the United States between 1988 and 1994, the authors selected 4,093 children (aged 6-17 years) for whom relevant medical, socioeconomic, and anthropometric data were complete. The children were 50.6% female, and 9.7% reported a diagnosis of asthma. Bivariate analyses showed that asthma diagnosis was associated with lower levels of serum vitamin C, alpha-carotene, beta-carotene, and beta-cryptoxanthin. However, antioxidant levels may be surrogate markers for socioeconomic variables such as race, poverty, tobacco exposure, or general nutritional status. In logistic models that included age, body mass index, socioeconomic variables, antioxidant levels, parental asthma, and household smoking, the only antioxidants significantly associated with asthma were vitamin C (odds ratio = 0.72 per mg/dl, 95% confidence interval = 0.55, 0.95) and alpha-carotene (odds ratio = 0.95 per mug/dl, 95% confidence interval = 0.90, 0.99). The odds ratio for asthma in the highest quintile of serum vitamin C relative to the lowest was 0.65 (p < 0.05), whereas it was 0.74 for &alpha;-carotene (p = 0.066). The authors concluded that low vitamin C and &alpha;-carotene intakes are associated with asthma risk in children.. adolescent| antioxidants| ascorbic acid| asthma| child|nutrition-examination-survey| national-health| ascorbic-acid| pulmonary-function| bronchial-asthma| alpha-tocopherol| responsiveness| antioxidants| consumption| histamine.	FEB 15-2004	adolescent| antioxidants| ascorbic acid| asthma| child|nutrition-examination-survey| national-health| ascorbic-acid| pulmonary-function| bronchial-asthma| alpha-tocopherol| responsiveness| antioxidants| consumption| histamine	Harik-Khan, RI; Muller, DC; Wise, RA	Serum vitamin levels and the risk of asthma in children		AMERICAN JOURNAL OF EPIDEMIOLOGY	adolescent; antioxidants; ascorbic acid; asthma; child	NUTRITION-EXAMINATION-SURVEY; NATIONAL-HEALTH; ASCORBIC-ACID; PULMONARY-FUNCTION; BRONCHIAL-ASTHMA; ALPHA-TOCOPHEROL; RESPONSIVENESS; ANTIOXIDANTS; CONSUMPTION; HISTAMINE	Dietary intake, especially of antioxidant vitamins A, C, E, and the carotenoids, has been linked with the presence and severity of asthma. From the Third National Health and Nutrition Examination Survey (NHANES III), conducted in the United States between 1988 and 1994, the authors selected 4,093 children (aged 6-17 years) for whom relevant medical, socioeconomic, and anthropometric data were complete. The children were 50.6% female, and 9.7% reported a diagnosis of asthma. Bivariate analyses showed that asthma diagnosis was associated with lower levels of serum vitamin C, alpha-carotene, beta-carotene, and beta-cryptoxanthin. However, antioxidant levels may be surrogate markers for socioeconomic variables such as race, poverty, tobacco exposure, or general nutritional status. In logistic models that included age, body mass index, socioeconomic variables, antioxidant levels, parental asthma, and household smoking, the only antioxidants significantly associated with asthma were vitamin C (odds ratio = 0.72 per mg/dl, 95% confidence interval = 0.55, 0.95) and alpha-carotene (odds ratio = 0.95 per mug/dl, 95% confidence interval = 0.90, 0.99). The odds ratio for asthma in the highest quintile of serum vitamin C relative to the lowest was 0.65 (p < 0.05), whereas it was 0.74 for &alpha;-carotene (p = 0.066). The authors concluded that low vitamin C and &alpha;-carotene intakes are associated with asthma risk in children.	32	80	2004	7	10.1093/aje/kwh053	Public, Environmental & Occupational Health
Seafood allergy and allergens: A review. Seafoods are composed of diverse sea organisms and humans are allergic to many of them. Tropomyosin is a major allergen in many shellfish, especially crustacea and mollusks. Interestingly, tropomyosin has also been identified as an important allergen in other invertebrates including dust mites and cockroaches, and it has been proposed by some to be an invertebrate pan allergen. Different regions of shrimp tropomyosin bind IgE; 5 major IgE-binding regions have been identified in shrimp tropomyosin containing 8 epitopes. Mutations of these shrimp allergenic epitopes can reduce seafood allergenicity; methods utilizing such mutations will provide safer vaccines for more effective treatment of seafood-allergic patients, and in the future less-allergenic seafood products for consumption.. seafood| shrimp| allergy| tropomyosin| epitopes| ige antibody reactivity|ige-binding epitopes| grass-pollen immunotherapy| muscle protein tropomyosin| cross-reactive allergen| crab-processing workers| culture-oyster workers| major shrimp allergen| salmon salmo-salar| occupational asthma| contact urticaria.	JUL-AUG-2003	seafood| shrimp| allergy| tropomyosin| epitopes| ige antibody reactivity|ige-binding epitopes| grass-pollen immunotherapy| muscle protein tropomyosin| cross-reactive allergen| crab-processing workers| culture-oyster workers| major shrimp allergen| salmon salmo-salar| occupational asthma| contact urticaria	Lehrer, SB; Ayuso, R; Reese, G	Seafood allergy and allergens: A review		MARINE BIOTECHNOLOGY	seafood; shrimp; allergy; tropomyosin; epitopes; IgE antibody reactivity	IGE-BINDING EPITOPES; GRASS-POLLEN IMMUNOTHERAPY; MUSCLE PROTEIN TROPOMYOSIN; CROSS-REACTIVE ALLERGEN; CRAB-PROCESSING WORKERS; CULTURE-OYSTER WORKERS; MAJOR SHRIMP ALLERGEN; SALMON SALMO-SALAR; OCCUPATIONAL ASTHMA; CONTACT URTICARIA	Seafoods are composed of diverse sea organisms and humans are allergic to many of them. Tropomyosin is a major allergen in many shellfish, especially crustacea and mollusks. Interestingly, tropomyosin has also been identified as an important allergen in other invertebrates including dust mites and cockroaches, and it has been proposed by some to be an invertebrate pan allergen. Different regions of shrimp tropomyosin bind IgE; 5 major IgE-binding regions have been identified in shrimp tropomyosin containing 8 epitopes. Mutations of these shrimp allergenic epitopes can reduce seafood allergenicity; methods utilizing such mutations will provide safer vaccines for more effective treatment of seafood-allergic patients, and in the future less-allergenic seafood products for consumption.	75	80	2003	10	10.1007/s10126-002-0082-1	Biotechnology & Applied Microbiology; Marine & Freshwater Biology
Effects of histamine on Th1/Th2 cytokine balance. Atopic asthma is a chronic inflammatory disorder of the airways where upon exposure to allergens, the body mounts an immune response. This disease is associated with an increase in the number of Th2 (T helper type 2) cells and Th2 cytokines and a decrease in the number of Th1 (T helper type 1) cells and Th1 cytokines. Histamine plays an important role in the pathogenesis of atopic asthma through differential regulation of T helper lymphocytes. Histamine enhances the secretion of Th2 cytokines such as IL-4 (interleukin-4), IL-5, IL-10 and IL-13 and inhibits the production of Th1 cytokines IL-2 and IFNgamma (interferon-gamma)and monokine IL-12. It has been shown that histamine can modulate the cytokine network through upregulation of PGE(2) (prostaglandin E-2) and NO (nitric oxide). Histamine also affects cytokine production via H2 receptors and through the activation of PKA (protein kinase A). We have also demonstrated that the Jak-STAT (Janus kinase-signal transducers and activators of transcription) pathway is involved in histamine-mediated regulation of Th2 cytokines IL-5, IL-10, IL-13 and Th1 cytokine IFNgamma. While standard treatment of asthma consists of beta-receptor agonists and inhaled corticosteroids, the elucidation of histamine's control over the cytokine network and the Th1/Th2 balance provides a basis for the potential use of antihistamines in the prevention and treatment of atopic asthma. Several other anti-allergic agents to modulate the Th1/Th2 balance are under current investigation based on this paradigm. These include cytokines, cytokine antagonists, anti-IgE, and vaccinations. As more advances are made in our understanding of histamine and its control over the Th1/Th2 balance, the use of new therapeutic targets such as these will play a prominent role in disease management. (C) 2003 Published by Elsevier Science B.V.. th1/th2| histamine| asthma|protein-kinase-a| recombinant interferon-gamma| allergic airway inflammation| natural suppressor cells| nitric-oxide synthase| human t-cells| ifn-gamma| th2 cells| signal-transduction| immune-response.	JUL-2003	th1/th2| histamine| asthma|protein-kinase-a| recombinant interferon-gamma| allergic airway inflammation| natural suppressor cells| nitric-oxide synthase| human t-cells| ifn-gamma| th2 cells| signal-transduction| immune-response	Packard, KA; Khan, MM	Effects of histamine on Th1/Th2 cytokine balance		INTERNATIONAL IMMUNOPHARMACOLOGY	Th1/Th2; histamine; asthma	PROTEIN-KINASE-A; RECOMBINANT INTERFERON-GAMMA; ALLERGIC AIRWAY INFLAMMATION; NATURAL SUPPRESSOR CELLS; NITRIC-OXIDE SYNTHASE; HUMAN T-CELLS; IFN-GAMMA; TH2 CELLS; SIGNAL-TRANSDUCTION; IMMUNE-RESPONSE	Atopic asthma is a chronic inflammatory disorder of the airways where upon exposure to allergens, the body mounts an immune response. This disease is associated with an increase in the number of Th2 (T helper type 2) cells and Th2 cytokines and a decrease in the number of Th1 (T helper type 1) cells and Th1 cytokines. Histamine plays an important role in the pathogenesis of atopic asthma through differential regulation of T helper lymphocytes. Histamine enhances the secretion of Th2 cytokines such as IL-4 (interleukin-4), IL-5, IL-10 and IL-13 and inhibits the production of Th1 cytokines IL-2 and IFNgamma (interferon-gamma)and monokine IL-12. It has been shown that histamine can modulate the cytokine network through upregulation of PGE(2) (prostaglandin E-2) and NO (nitric oxide). Histamine also affects cytokine production via H2 receptors and through the activation of PKA (protein kinase A). We have also demonstrated that the Jak-STAT (Janus kinase-signal transducers and activators of transcription) pathway is involved in histamine-mediated regulation of Th2 cytokines IL-5, IL-10, IL-13 and Th1 cytokine IFNgamma. While standard treatment of asthma consists of beta-receptor agonists and inhaled corticosteroids, the elucidation of histamine's control over the cytokine network and the Th1/Th2 balance provides a basis for the potential use of antihistamines in the prevention and treatment of atopic asthma. Several other anti-allergic agents to modulate the Th1/Th2 balance are under current investigation based on this paradigm. These include cytokines, cytokine antagonists, anti-IgE, and vaccinations. As more advances are made in our understanding of histamine and its control over the Th1/Th2 balance, the use of new therapeutic targets such as these will play a prominent role in disease management. (C) 2003 Published by Elsevier Science B.V.	85	80	2003	12	10.1016/S1567-5769(02)00235-7	Immunology; Pharmacology & Pharmacy
Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice. Our previous studies indicated that intramuscular (i.m.) immunisation with full length Der p 1 cDNA induced significant humoral response to the left domain (approximately corresponding to amino acids 1-116) but not to the right domain (approximately corresponding to amino acids 117-222) of Der p I allergen. This study explored the use of chitosan-DNA nanoparticles for oral immunisation to induce immune responses specific to both the left and right domains of Der p 1. DNA constructs pDer p 1 (1-222) and pDer p 1 (114-222) were complexed with chitosan and delivered orally followed by an i.m. injection of pDer p 1 (1-222) 13 weeks later. Such approach has successfully primed Th1-skewed immune responses against both domains of Der p 1. This strategy could be further optimised for more efficacious gene vaccination for full length Der p 1. (C) 2003 Elsevier Science Ltd. All rights reserved.. oral| chitosan nanoparticles| der p 1|hiv envelope glycoprotein| systemic immune-responses| murine peyers-patches| in-vivo uptake| der-p-i| gene-transfer| dermatophagoides-pteronyssinus| biodegradable microparticles| mucosal immunization| antibody-responses.	JUN 20-2003	oral| chitosan nanoparticles| der p 1|hiv envelope glycoprotein| systemic immune-responses| murine peyers-patches| in-vivo uptake| der-p-i| gene-transfer| dermatophagoides-pteronyssinus| biodegradable microparticles| mucosal immunization| antibody-responses	Chew, JL; Wolfowicz, CB; Mao, HQ; Leong, KW; Chua, KY	Chitosan nanoparticles containing plasmid DNA encoding house dust mite allergen, Der p 1 for oral vaccination in mice		VACCINE	oral; chitosan nanoparticles; Der p 1	HIV ENVELOPE GLYCOPROTEIN; SYSTEMIC IMMUNE-RESPONSES; MURINE PEYERS-PATCHES; IN-VIVO UPTAKE; DER-P-I; GENE-TRANSFER; DERMATOPHAGOIDES-PTERONYSSINUS; BIODEGRADABLE MICROPARTICLES; MUCOSAL IMMUNIZATION; ANTIBODY-RESPONSES	Our previous studies indicated that intramuscular (i.m.) immunisation with full length Der p 1 cDNA induced significant humoral response to the left domain (approximately corresponding to amino acids 1-116) but not to the right domain (approximately corresponding to amino acids 117-222) of Der p I allergen. This study explored the use of chitosan-DNA nanoparticles for oral immunisation to induce immune responses specific to both the left and right domains of Der p 1. DNA constructs pDer p 1 (1-222) and pDer p 1 (114-222) were complexed with chitosan and delivered orally followed by an i.m. injection of pDer p 1 (1-222) 13 weeks later. Such approach has successfully primed Th1-skewed immune responses against both domains of Der p 1. This strategy could be further optimised for more efficacious gene vaccination for full length Der p 1. (C) 2003 Elsevier Science Ltd. All rights reserved.	46	80	2003	10	10.1016/S0264-410X(03)00228-7	Immunology; Research & Experimental Medicine
"Methods for ""indirect"" challenge tests including exercise, eucapnic voluntary hyperpnea, and hypertonic aerosols. Bronchial provocation tests that use stimuli that act indirectly to cause airway narrowing have a high specificity for identifying people with active asthma who have the potential to respond to treatment with antiinflammatory drugs. The first test to be developed was exercise and it was used to assess the efficacy of drugs such as sodium cromoglycate. Eucapnic voluntary hyperpnea was developed later, as a surrogate test for exercise. Hypertonic aerosols were introduced to mimic the dehydrating effects of evaporative water loss that occurs during hyperpnea. A wet aerosol of 4.5% saline or a dry powder formulation of mannitol is used. At present the indirect challenge tests are becoming increasingly recognised as appropriate for monitoring treatment with inhaled steroids. Indirect tests identify those with potential for exercise-induced bronchoconstriction, an important problem for some occupations, such as the defence forces, fire fighters and the police force and for some athletic activities. The advantage in using an indirect challenges, over a direct challenge with a single pharmacological agonist, is that a positive response indicates that inflammatory cells and their mediators (prostaglandins, leukotrienes and histamine) are present in the airways in sufficient numbers and concentration to indicate that asthma is active at the time of testing. The corollary to this is that a negative test in a known asthmatic indicates good control or mild disease. Another advantage is that healthy subjects do not have significant airway narrowing to indirect challenge tests. The protocols used for challenge with indirectly acting stimuli are presented in detail.. exercise| dry air hyperpnea| mannitol| hypertonic saline|ultrasonically nebulized solutions| inhaled corticosteroid budesonide| hyperventilation-induced asthma| working party standardization| european respiratory society| cold-air hyperventilation| thermally-induced asthma| long-term treatment| induced bronchoconstriction| bronchial responsiveness."	FEB-2003	exercise| dry air hyperpnea| mannitol| hypertonic saline|ultrasonically nebulized solutions| inhaled corticosteroid budesonide| hyperventilation-induced asthma| working party standardization| european respiratory society| cold-air hyperventilation| thermally-induced asthma| long-term treatment| induced bronchoconstriction| bronchial responsiveness	Anderson, SD; Brannan, JD	"Methods for ""indirect"" challenge tests including exercise, eucapnic voluntary hyperpnea, and hypertonic aerosols"		CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY	exercise; dry air hyperpnea; mannitol; hypertonic saline	ULTRASONICALLY NEBULIZED SOLUTIONS; INHALED CORTICOSTEROID BUDESONIDE; HYPERVENTILATION-INDUCED ASTHMA; WORKING PARTY STANDARDIZATION; EUROPEAN RESPIRATORY SOCIETY; COLD-AIR HYPERVENTILATION; THERMALLY-INDUCED ASTHMA; LONG-TERM TREATMENT; INDUCED BRONCHOCONSTRICTION; BRONCHIAL RESPONSIVENESS	Bronchial provocation tests that use stimuli that act indirectly to cause airway narrowing have a high specificity for identifying people with active asthma who have the potential to respond to treatment with antiinflammatory drugs. The first test to be developed was exercise and it was used to assess the efficacy of drugs such as sodium cromoglycate. Eucapnic voluntary hyperpnea was developed later, as a surrogate test for exercise. Hypertonic aerosols were introduced to mimic the dehydrating effects of evaporative water loss that occurs during hyperpnea. A wet aerosol of 4.5% saline or a dry powder formulation of mannitol is used. At present the indirect challenge tests are becoming increasingly recognised as appropriate for monitoring treatment with inhaled steroids. Indirect tests identify those with potential for exercise-induced bronchoconstriction, an important problem for some occupations, such as the defence forces, fire fighters and the police force and for some athletic activities. The advantage in using an indirect challenges, over a direct challenge with a single pharmacological agonist, is that a positive response indicates that inflammatory cells and their mediators (prostaglandins, leukotrienes and histamine) are present in the airways in sufficient numbers and concentration to indicate that asthma is active at the time of testing. The corollary to this is that a negative test in a known asthmatic indicates good control or mild disease. Another advantage is that healthy subjects do not have significant airway narrowing to indirect challenge tests. The protocols used for challenge with indirectly acting stimuli are presented in detail.	153	80	2003	28	10.1385/CRIAI:24:1:27	Allergy; Immunology
A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae. Background: We cultured Dermatophagoides farinae (Df), one of the most common mites in house dust and the most important allergen among natural allergens. With this material, we attempted to produce an animal model of the atopic eczema/dermatitis syndrome (AEDS). Methods: We cultured Df mites in high density and prepared a crude extract of Df (DfE) together with the culture medium. We applied the extract to the back skin of NC/Nga and BALB/c mice three times per week for 8 weeks. Results: In the NC/Nga group, dryness or scaling appeared on the skin, and scratching behavior increased at the second week in the DfE-treated group. Skin erosion and hemorrhage occurred at the fourth week. The epidermis thickened and deepened into the upper dermis, in which mast cells were highly accumulated, corresponding with the skin lesion of AEDS patients. Specific IgE and IgG to DfE and total IgE were elevated in the sera. Mice treated with an extract of mite culture medium did not develop skin lesions. In the BALB/c group, mice developed specific IgE and IgG to DfE, however, no typical skin lesions appeared. Mast cells in the upper dermis did not increase. Conclusions: Repeated painting of Dermatophagoides extract produced IgE-associated AEDS-like lesions on the skin of NC mice.. atopic eczema/dermatitis syndrome| dermatophagoides farinae| ige| mast cell| mouse model|epidermal langerhans cells| regional lymph-nodes| ige hyperproduction| nc/nga mice| dermatitis| sensitization| antibodies| population| allergens| antigen.	FEB-2003	atopic eczema/dermatitis syndrome| dermatophagoides farinae| ige| mast cell| mouse model|epidermal langerhans cells| regional lymph-nodes| ige hyperproduction| nc/nga mice| dermatitis| sensitization| antibodies| population| allergens| antigen	Matsuoka, H; Maki, N; Yoshida, S; Arai, M; Wang, J; Oikawa, Y; Ikeda, T; Hirota, N; Nakagawa, H; Ishii, A	A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house-dust mite Dermatophagoides farinae		ALLERGY	atopic eczema/dermatitis syndrome; Dermatophagoides farinae; IgE; mast cell; mouse model	EPIDERMAL LANGERHANS CELLS; REGIONAL LYMPH-NODES; IGE HYPERPRODUCTION; NC/NGA MICE; DERMATITIS; SENSITIZATION; ANTIBODIES; POPULATION; ALLERGENS; ANTIGEN	Background: We cultured Dermatophagoides farinae (Df), one of the most common mites in house dust and the most important allergen among natural allergens. With this material, we attempted to produce an animal model of the atopic eczema/dermatitis syndrome (AEDS). Methods: We cultured Df mites in high density and prepared a crude extract of Df (DfE) together with the culture medium. We applied the extract to the back skin of NC/Nga and BALB/c mice three times per week for 8 weeks. Results: In the NC/Nga group, dryness or scaling appeared on the skin, and scratching behavior increased at the second week in the DfE-treated group. Skin erosion and hemorrhage occurred at the fourth week. The epidermis thickened and deepened into the upper dermis, in which mast cells were highly accumulated, corresponding with the skin lesion of AEDS patients. Specific IgE and IgG to DfE and total IgE were elevated in the sera. Mice treated with an extract of mite culture medium did not develop skin lesions. In the BALB/c group, mice developed specific IgE and IgG to DfE, however, no typical skin lesions appeared. Mast cells in the upper dermis did not increase. Conclusions: Repeated painting of Dermatophagoides extract produced IgE-associated AEDS-like lesions on the skin of NC mice.	25	80	2003	7	10.1034/j.1398-9995.2003.23790.x	Allergy; Immunology
Inhaled fluticasone decreases bronchial but not alveolar nitric oxide output in asthma. Exhaled nitric oxide (NO) concentration is a noninvasive measure of airway inflammation and is increased in asthma. Inhaled glucocorticoids decrease exhaled NO concentration, but the relative contributions of alveolar and bronchial levels to the decrease in exhaled NO concentration are unknown. Alveolar NO concentration and bronchial NO flux can be separately approximated by measuring exhaled NO at several exhalation flow rates. The effect of steroid treatment on alveolar and bronchial NO output in asthma was studied. Alveolar NO concentration and bronchial NO flux were assessed in 16 patients with asthma before and during treatment with inhaled fluticasone for 8 weeks and in 16 healthy controls. Before the treatment, asthmatics had increased bronchial NO flux (mean +/- SEM: 3.6 +/-0.4 versus 0.7 +/-0.1 nL.s(-1), p<0.001) but normal alveolar NO concentration (1.2<plus/minus>0.5 versus 1.0 +/-0.2 parts per billion (ppb), p>0.05) compared with controls Inhaled fluticasone decreased bronchial NO flux from 3.6 +/-0.4 to 0.7 +/-0.1 nL.s(-1)(p<0.01) but had no effect on alveolar NO concentration (before: 1.2<plus/minus>0.5; after: 1.2 +/-0.1 ppb, p>0.05). The forced expiratory volume in one second improved, whereas asthma symptom score and serum levels of eosinophil cationic protein and eosinophil protein X decreased during the treatment. In conclusion, inhaled fluticasone decreases bronchial but not alveolar nitric oxide output simultaneously with clinical improvement in patients with asthma.. asthma| eosinophil cationic protein| eosinophil protein x| exhaled nitric oxide| inflammation| inhaled glucocorticoids|exhaled air| sputum eosinophils| mild asthma| induction| synthase| airways| responsiveness| inflammation.	OCT-2001	asthma| eosinophil cationic protein| eosinophil protein x| exhaled nitric oxide| inflammation| inhaled glucocorticoids|exhaled air| sputum eosinophils| mild asthma| induction| synthase| airways| responsiveness| inflammation	Lehtimaki, L; Kankaanranta, H; Saarelainen, S; Turjanmaa, V; Moilanen, E	Inhaled fluticasone decreases bronchial but not alveolar nitric oxide output in asthma		EUROPEAN RESPIRATORY JOURNAL	asthma; eosinophil cationic protein; eosinophil protein X; exhaled nitric oxide; inflammation; inhaled glucocorticoids	EXHALED AIR; SPUTUM EOSINOPHILS; MILD ASTHMA; INDUCTION; SYNTHASE; AIRWAYS; RESPONSIVENESS; INFLAMMATION	Exhaled nitric oxide (NO) concentration is a noninvasive measure of airway inflammation and is increased in asthma. Inhaled glucocorticoids decrease exhaled NO concentration, but the relative contributions of alveolar and bronchial levels to the decrease in exhaled NO concentration are unknown. Alveolar NO concentration and bronchial NO flux can be separately approximated by measuring exhaled NO at several exhalation flow rates. The effect of steroid treatment on alveolar and bronchial NO output in asthma was studied. Alveolar NO concentration and bronchial NO flux were assessed in 16 patients with asthma before and during treatment with inhaled fluticasone for 8 weeks and in 16 healthy controls. Before the treatment, asthmatics had increased bronchial NO flux (mean +/- SEM: 3.6 +/-0.4 versus 0.7 +/-0.1 nL.s(-1), p<0.001) but normal alveolar NO concentration (1.2<plus/minus>0.5 versus 1.0 +/-0.2 parts per billion (ppb), p>0.05) compared with controls Inhaled fluticasone decreased bronchial NO flux from 3.6 +/-0.4 to 0.7 +/-0.1 nL.s(-1)(p<0.01) but had no effect on alveolar NO concentration (before: 1.2<plus/minus>0.5; after: 1.2 +/-0.1 ppb, p>0.05). The forced expiratory volume in one second improved, whereas asthma symptom score and serum levels of eosinophil cationic protein and eosinophil protein X decreased during the treatment. In conclusion, inhaled fluticasone decreases bronchial but not alveolar nitric oxide output simultaneously with clinical improvement in patients with asthma.	20	80	2001	5	10.1183/09031936.01.00000201	Respiratory System
Hospitalization rates for respiratory syncytial virus infection in premature infants born during two consecutive seasons. Objective. To collect data on hospitalization rates for respiratory syncytial virus (RSV) illness during the season of 1999 to 2000 in nonprophylaxed premature infants less than or equal to 32 weeks gestational age (GA) in Spain and compare this with previously published data collected in the season of 1998 to 1999. Methods. Children born at less than or equal to 32 weeks GA between April 1, 1999, and April 31, 2000, and discharged from the hospital before April 31, 2000, were included. Neonatal and demographic data were obtained at the initial visit. Study subjects were followed at monthly intervals throughout the respiratory season. RSV status and morbidity data were collected on patients rehospitalized for respiratory illness. Results. The 999 evaluable patients in the 2000 season were comparable to the 1999 sample, except for higher rates of family allergy history and number of multiple deliveries and a lower rate of neonatal morbidity. The hospitalization rate for RSV illness was 13.4% in the 1999 season and 13.1% in the 2000 season; 10 (8%) were RSV reinfections in the 2000 season. Significant independent prognostic variables for high risk of RSV hospital admission included: lower gestational age; chronologic age <3 months at onset of the RSV season; living with school age siblings; and exposure to tobacco smoke. Conclusions. Hospitalization rates for RSV disease in nonprophylaxed preterm infants less than or equal to 32 weeks GA were high in Spain and comparable during two consecutive RSV seasons (13%). Readmission for a second RSV infection was also common.. respiratory syncytial virus| premature infants| hospitalization| epidemiology|rehospitalization| gestation| children.	SEP-2001	respiratory syncytial virus| premature infants| hospitalization| epidemiology|rehospitalization| gestation| children	Carbonell-Estrany, X; Quero, J	Hospitalization rates for respiratory syncytial virus infection in premature infants born during two consecutive seasons		PEDIATRIC INFECTIOUS DISEASE JOURNAL	respiratory syncytial virus; premature infants; hospitalization; epidemiology	REHOSPITALIZATION; GESTATION; CHILDREN	Objective. To collect data on hospitalization rates for respiratory syncytial virus (RSV) illness during the season of 1999 to 2000 in nonprophylaxed premature infants less than or equal to 32 weeks gestational age (GA) in Spain and compare this with previously published data collected in the season of 1998 to 1999. Methods. Children born at less than or equal to 32 weeks GA between April 1, 1999, and April 31, 2000, and discharged from the hospital before April 31, 2000, were included. Neonatal and demographic data were obtained at the initial visit. Study subjects were followed at monthly intervals throughout the respiratory season. RSV status and morbidity data were collected on patients rehospitalized for respiratory illness. Results. The 999 evaluable patients in the 2000 season were comparable to the 1999 sample, except for higher rates of family allergy history and number of multiple deliveries and a lower rate of neonatal morbidity. The hospitalization rate for RSV illness was 13.4% in the 1999 season and 13.1% in the 2000 season; 10 (8%) were RSV reinfections in the 2000 season. Significant independent prognostic variables for high risk of RSV hospital admission included: lower gestational age; chronologic age <3 months at onset of the RSV season; living with school age siblings; and exposure to tobacco smoke. Conclusions. Hospitalization rates for RSV disease in nonprophylaxed preterm infants less than or equal to 32 weeks GA were high in Spain and comparable during two consecutive RSV seasons (13%). Readmission for a second RSV infection was also common.	20	80	2001	6	10.1097/00006454-200109000-00010	Immunology; Infectious Diseases; Pediatrics
Environmental tobacco smoke exposure during childhood is associated with increased prevalence of asthma in adults. Objective: To examine if exposure to environmental tobacco smoke (ETS) during childhood has an impact on asthma prevalence in adults, and to identify the amount of nuisance from ETS and other lower airway irritants (LAWIs) in a city population. Design: A postal survey. Setting: The municipality of Orebro, Sweden. Participants: A total of 8,008 randomly selected inhabitants aged 15 to 69 years. Measurements: Exposures, airway symptoms, and respiratory history were assessed using a questionnaire. Results: The response rate was 84%. In never-smokers with childhood ETS exposure, the prevalence of physician-diagnosed asthma was 7.6% vs 5.9% in nonexposed subjects (p = 0.036). In never-smokers without a family history of asthma, the prevalence of physician-diagnosed asthma in subjects reporting childhood ETS exposure was 6.8% vs 3.8% in nonexposed subjects (p < 0.001). Subjects with childhood ETS exposure were more likely to start smoking in adulthood. The prevalence of ever-smokers was 54.5% vs 33.8% (p < 0.0001) in nonexposed subjects. ETS was the most commonly reported LAWI in the total sample (21%), followed by exercise in cold air (20%); dust (19%), exercise (16%), perfume (15%), cold air (12%), pollen (10%), and pets (8%). All LAWIs were more frequently reported by women. Conclusions: Childhood exposure to ETS is associated with an increased prevalence of asthma among adult never-smokers, especially in nonatopic subjects. Children exposed to ETS are also more likely to become smokers. ETS is as a major LAWI.. asthma| environmental tobacco smoke| respiratory symptoms|passive smoking| disease| life| risk.	SEP-2001	asthma| environmental tobacco smoke| respiratory symptoms|passive smoking| disease| life| risk	Larsson, ML; Frisk, M; Hallstrom, J; Kiviloog, J; Lundback, B	Environmental tobacco smoke exposure during childhood is associated with increased prevalence of asthma in adults		CHEST	asthma; environmental tobacco smoke; respiratory symptoms	PASSIVE SMOKING; DISEASE; LIFE; RISK	Objective: To examine if exposure to environmental tobacco smoke (ETS) during childhood has an impact on asthma prevalence in adults, and to identify the amount of nuisance from ETS and other lower airway irritants (LAWIs) in a city population. Design: A postal survey. Setting: The municipality of Orebro, Sweden. Participants: A total of 8,008 randomly selected inhabitants aged 15 to 69 years. Measurements: Exposures, airway symptoms, and respiratory history were assessed using a questionnaire. Results: The response rate was 84%. In never-smokers with childhood ETS exposure, the prevalence of physician-diagnosed asthma was 7.6% vs 5.9% in nonexposed subjects (p = 0.036). In never-smokers without a family history of asthma, the prevalence of physician-diagnosed asthma in subjects reporting childhood ETS exposure was 6.8% vs 3.8% in nonexposed subjects (p < 0.001). Subjects with childhood ETS exposure were more likely to start smoking in adulthood. The prevalence of ever-smokers was 54.5% vs 33.8% (p < 0.0001) in nonexposed subjects. ETS was the most commonly reported LAWI in the total sample (21%), followed by exercise in cold air (20%); dust (19%), exercise (16%), perfume (15%), cold air (12%), pollen (10%), and pets (8%). All LAWIs were more frequently reported by women. Conclusions: Childhood exposure to ETS is associated with an increased prevalence of asthma among adult never-smokers, especially in nonatopic subjects. Children exposed to ETS are also more likely to become smokers. ETS is as a major LAWI.	23	80	2001	7	10.1378/chest.120.3.711	General & Internal Medicine; Respiratory System
Asthma severity, atopic status, allergen exposure, and quality of life in elderly persons. Background: Although asthma can be associated with significant airflow obstruction in those over the age of 65, it is often underdiagnosed and undertreated. Objective: To describe severity of asthma, allergy skin test sensitivities, indoor allergen exposures, and the impact on quality of life (QOL) and health status in elderly persons with asthma. Methods: A cross-sectional data analysis with 80 elderly persons with asthma recruited from medical, geriatric, and allergy/immunology tertiary care centers. Asthma severity was determined by symptoms and measurements of lung function. House dust specimens were collected from mattresses and bedroom carpets and analyzed separately for the major allergens of house dust, using monoclonal antibody-based immunoenzymetric assays. QOL was measured using Juniper's Asthma Quality of Life Questionnaire. Health status was measured using the Short Form Health Survey Medical Outcome Questionnaire which included Ferrans and Powers' Quality of Life Index subscales. Results: Two-thirds of participants had either moderate or severe persistent asthma. Skin tests to a battery of common airborne allergens were positive to at least one allergen in 56 of the 75 participants tested (74.7%). Reservoir dust allergen levels were often high enough to place participants at risk of symptoms or at risk of developing sensitization. Increased asthma severity was associated with significantly lower QOL and a trend toward decreased health status. Conclusions: Asthma is a significant chronic problem in the elderly. Atopy was common. Asthma severity impacts on these participants' QOL and health status. Results support interventions aimed at identifying allergens precipitating attacks and reducing them in the home.. inner-city children| dust mite allergens| indoor allergens| international workshop| risk factor| of-life| sensitization| adults| population| childhood.	MAY-2001	inner-city children| dust mite allergens| indoor allergens| international workshop| risk factor| of-life| sensitization| adults| population| childhood	Huss, K; Naumann, PL; Mason, PJ; Nanda, JP; Huss, RW; Smith, CM; Hamilton, RG	Asthma severity, atopic status, allergen exposure, and quality of life in elderly persons		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		INNER-CITY CHILDREN; DUST MITE ALLERGENS; INDOOR ALLERGENS; INTERNATIONAL WORKSHOP; RISK FACTOR; OF-LIFE; SENSITIZATION; ADULTS; POPULATION; CHILDHOOD	Background: Although asthma can be associated with significant airflow obstruction in those over the age of 65, it is often underdiagnosed and undertreated. Objective: To describe severity of asthma, allergy skin test sensitivities, indoor allergen exposures, and the impact on quality of life (QOL) and health status in elderly persons with asthma. Methods: A cross-sectional data analysis with 80 elderly persons with asthma recruited from medical, geriatric, and allergy/immunology tertiary care centers. Asthma severity was determined by symptoms and measurements of lung function. House dust specimens were collected from mattresses and bedroom carpets and analyzed separately for the major allergens of house dust, using monoclonal antibody-based immunoenzymetric assays. QOL was measured using Juniper's Asthma Quality of Life Questionnaire. Health status was measured using the Short Form Health Survey Medical Outcome Questionnaire which included Ferrans and Powers' Quality of Life Index subscales. Results: Two-thirds of participants had either moderate or severe persistent asthma. Skin tests to a battery of common airborne allergens were positive to at least one allergen in 56 of the 75 participants tested (74.7%). Reservoir dust allergen levels were often high enough to place participants at risk of symptoms or at risk of developing sensitization. Increased asthma severity was associated with significantly lower QOL and a trend toward decreased health status. Conclusions: Asthma is a significant chronic problem in the elderly. Atopy was common. Asthma severity impacts on these participants' QOL and health status. Results support interventions aimed at identifying allergens precipitating attacks and reducing them in the home.	31	80	2001	7		Allergy; Immunology
Spatial Poisson regression for health and exposure data measured at disparate resolutions. Ecological regression studies are widely used to examine relationships between disease rates for small geographical areas and exposure to environmental risk factors. The raw data for such studies, including disease cases, environmental pollution concentrations, and the reference population at risk, are typically measured at various levels of spatial aggregation but are accumulated to a common geographical scale to facilitate statistical analysis. In this traditional approach, heterogeneous exposure distributions within the aggregate areas may lead to biased inference, whereas individual attributes such as age, gender, and smoking habits must either be summarized to provide area-level covariate values or used to stratify the analysis. This article presents a spatial regression analysis of the effect of traffic pollution on respiratory disorders in children. The analysis features data measured at disparate, nonnested scales, including spatially varying covariates, latent spatially varying risk factors, and case-specific individual attributes. The problem of disparate discretizations is overcome by relating all spatially varying quantities to a continuous underlying random field model. Case-specific individual attributes are accommodated by treating cases as a marked point process. Inference in these hierarchical Poisson/gamma models is based on simulated samples drawn from Bayesian posterior distributions, using Markov chain Monte Carlo methods with data augmentation.. air pollution| bayesian hierarchical models| continuous random fields| ecological regression| environmental epidemiology| respiratory illness|air-pollution| respiratory health| asthma| children| prevalence| statistics| motorways| mortality| symptoms| models.	DEC-2000	air pollution| bayesian hierarchical models| continuous random fields| ecological regression| environmental epidemiology| respiratory illness|air-pollution| respiratory health| asthma| children| prevalence| statistics| motorways| mortality| symptoms| models	Best, NG; Ickstadt, K; Wolpert, RL	Spatial Poisson regression for health and exposure data measured at disparate resolutions		JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION	air pollution; Bayesian hierarchical models; continuous random fields; ecological regression; environmental epidemiology; respiratory illness	AIR-POLLUTION; RESPIRATORY HEALTH; ASTHMA; CHILDREN; PREVALENCE; STATISTICS; MOTORWAYS; MORTALITY; SYMPTOMS; MODELS	Ecological regression studies are widely used to examine relationships between disease rates for small geographical areas and exposure to environmental risk factors. The raw data for such studies, including disease cases, environmental pollution concentrations, and the reference population at risk, are typically measured at various levels of spatial aggregation but are accumulated to a common geographical scale to facilitate statistical analysis. In this traditional approach, heterogeneous exposure distributions within the aggregate areas may lead to biased inference, whereas individual attributes such as age, gender, and smoking habits must either be summarized to provide area-level covariate values or used to stratify the analysis. This article presents a spatial regression analysis of the effect of traffic pollution on respiratory disorders in children. The analysis features data measured at disparate, nonnested scales, including spatially varying covariates, latent spatially varying risk factors, and case-specific individual attributes. The problem of disparate discretizations is overcome by relating all spatially varying quantities to a continuous underlying random field model. Case-specific individual attributes are accommodated by treating cases as a marked point process. Inference in these hierarchical Poisson/gamma models is based on simulated samples drawn from Bayesian posterior distributions, using Markov chain Monte Carlo methods with data augmentation.	51	80	2000	13	10.2307/2669744	Mathematics
Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?. In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro-inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T-cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro-activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.. airway smooth muscle| asthma| bronchial hyperresponsiveness| chemokines| proliferation|intercellular-adhesion molecule-1| repeated allergen exposure| brown-norway rats| growth-factor| dna synthesis| bronchoalveolar lavage| passive sensitization| t-helper-2 cytokines| asthmatic subjects| icam-1 expression.	MAY-2000	airway smooth muscle| asthma| bronchial hyperresponsiveness| chemokines| proliferation|intercellular-adhesion molecule-1| repeated allergen exposure| brown-norway rats| growth-factor| dna synthesis| bronchoalveolar lavage| passive sensitization| t-helper-2 cytokines| asthmatic subjects| icam-1 expression	Chung, KF	Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation?		EUROPEAN RESPIRATORY JOURNAL	airway smooth muscle; asthma; bronchial hyperresponsiveness; chemokines; proliferation	INTERCELLULAR-ADHESION MOLECULE-1; REPEATED ALLERGEN EXPOSURE; BROWN-NORWAY RATS; GROWTH-FACTOR; DNA SYNTHESIS; BRONCHOALVEOLAR LAVAGE; PASSIVE SENSITIZATION; T-HELPER-2 CYTOKINES; ASTHMATIC SUBJECTS; ICAM-1 EXPRESSION	In addition to its contractile properties, airway smooth muscle may contribute to the pathogenesis of asthma by increased proliferation, and by the expression and secretion of pro-inflammatory cytokines and mediators. Studies of airway smooth muscle cells in culture have shown that many mitogenic mediators can induce proliferation, and that these may therefore, contribute to the increase in airway smooth muscle mass observed in asthma. Other mechanisms for airway smooth muscle proliferation include the interaction with inflammatory cells such as T-cells and eosinophils. Airway smooth muscle cells may also be a source of inflammatory mediators and cytokines, in particular chemokines, thus implicating airway smooth muscle cells as contributors to the inflammatory mechanisms of asthma. The pro-activating signals for converting airway smooth muscle cells into a proliferative and secretory cell in asthma are unknown, but may include viruses and immunoglobulin E. Airway smooth muscle contractility may also be altered in response to inflammation. Airway smooth muscle cells may play an important interactive role with inflammatory and other structural cells, contributing to inflammation, injury and repair of the airways. Such a recognition makes it imperative to consider the airway smooth muscle as a target of therapeutic drugs for suppressing not only the contractile but also the proliferative and secretory effects of asthma.	85	80	2000	8	10.1034/j.1399-3003.2000.15e26.x	Respiratory System
The importance of exposure estimation in the assessment of skin sensitization risk. The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazoline/methylisothiazolinone (MCI/MI) as a case study.. skin| contact allergy| exposure| risk assessment| cosmetics| household products| dose per unit area|lymph-node assay| allergic contact sensitization| sodium lauryl sulfate| dose-response assessments| kathon biocide| guinea-pigs| patch tests| area| pretreatment| sensitivity.	MAY-2000	skin| contact allergy| exposure| risk assessment| cosmetics| household products| dose per unit area|lymph-node assay| allergic contact sensitization| sodium lauryl sulfate| dose-response assessments| kathon biocide| guinea-pigs| patch tests| area| pretreatment| sensitivity	Robinson, MK; Gerberick, GF; Ryan, CA; McNamee, P; White, IR; Basketter, DA	The importance of exposure estimation in the assessment of skin sensitization risk		CONTACT DERMATITIS	skin; contact allergy; exposure; risk assessment; cosmetics; household products; dose per unit area	LYMPH-NODE ASSAY; ALLERGIC CONTACT SENSITIZATION; SODIUM LAURYL SULFATE; DOSE-RESPONSE ASSESSMENTS; KATHON BIOCIDE; GUINEA-PIGS; PATCH TESTS; AREA; PRETREATMENT; SENSITIVITY	The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazoline/methylisothiazolinone (MCI/MI) as a case study.	53	80	2000	9	10.1034/j.1600-0536.2000.042005251.x	Allergy; Dermatology
Parental factors affecting respiratory function during the first year of life. In a prospective, longitudinal, population-based cohort study of familial and environmental influences on the development of wheezing respiratory illness in early childhood, we identified infant length, weight, gender, and exposure to maternal cigarette smoking as significant determinants of lung function during the first year of life. A cohort of 237 infants (106 females: 131 males) was evaluated, and 496 lung function measurements were made between the ages of 1-12 months. Respiratory function was assessed using the rapid thoracic compression technique to obtain maximum expiratory flow at functional residual capacity (V'maxFRC). Parental history of asthma and smoking habits during pregnancy were obtained by questionnaire. Data were analyzed using a longitudinal random effects model. infants with a parental history of asthma and/or in utero passive smoke exposure were compared to a reference group of infants who had no parental history of asthma and in whom neither parent smoked pre- or postnatally. Boys were found to have a consistently lower V'maxFRC (-21.05 mL.s(-1)) throughout the first year of life in comparison to girls (P < 0.05). Maternal smoking during pregnancy was associated with a lower V'maxFRG in both genders in comparison to unexposed infants (P < 0.05). V'maxFRC was unaffected by parental history of asthma. Gender-specific normative equations for V'maxFRC throughout the first year of life were derived for the infant cohort as a whole and also for subgroups of infants, based on parental asthma and smoking history. We conclude that lung function during the first year of life differs between genders and is adversely affected by in utero passive tobacco smoke exposure. Gender-specific predictive equations for V'maxFRG should be used during infancy. Pediatr Pulmonol. 2000; 29:331-340, (C) 2000 Wiley-Liss, Inc.. infant lung function| maternal tobacco smoking| in utero tobacco smoke exposure| maternal inheritance| infant gender| predictive equations| asthma|flow-volume curves| forced expiratory flows| pulmonary-function| maternal smoking| lung-function| 1st year| passive smoking| normal infants| longitudinal data| newborn-infants.	MAY-2000	infant lung function| maternal tobacco smoking| in utero tobacco smoke exposure| maternal inheritance| infant gender| predictive equations| asthma|flow-volume curves| forced expiratory flows| pulmonary-function| maternal smoking| lung-function| 1st year| passive smoking| normal infants| longitudinal data| newborn-infants	Young, S; Sherrill, DL; Arnott, J; Diepeveen, D; LeSouef, PN; Landau, LI	Parental factors affecting respiratory function during the first year of life		PEDIATRIC PULMONOLOGY	infant lung function; maternal tobacco smoking; in utero tobacco smoke exposure; maternal inheritance; infant gender; predictive equations; asthma	FLOW-VOLUME CURVES; FORCED EXPIRATORY FLOWS; PULMONARY-FUNCTION; MATERNAL SMOKING; LUNG-FUNCTION; 1ST YEAR; PASSIVE SMOKING; NORMAL INFANTS; LONGITUDINAL DATA; NEWBORN-INFANTS	In a prospective, longitudinal, population-based cohort study of familial and environmental influences on the development of wheezing respiratory illness in early childhood, we identified infant length, weight, gender, and exposure to maternal cigarette smoking as significant determinants of lung function during the first year of life. A cohort of 237 infants (106 females: 131 males) was evaluated, and 496 lung function measurements were made between the ages of 1-12 months. Respiratory function was assessed using the rapid thoracic compression technique to obtain maximum expiratory flow at functional residual capacity (V'maxFRC). Parental history of asthma and smoking habits during pregnancy were obtained by questionnaire. Data were analyzed using a longitudinal random effects model. infants with a parental history of asthma and/or in utero passive smoke exposure were compared to a reference group of infants who had no parental history of asthma and in whom neither parent smoked pre- or postnatally. Boys were found to have a consistently lower V'maxFRC (-21.05 mL.s(-1)) throughout the first year of life in comparison to girls (P < 0.05). Maternal smoking during pregnancy was associated with a lower V'maxFRG in both genders in comparison to unexposed infants (P < 0.05). V'maxFRC was unaffected by parental history of asthma. Gender-specific normative equations for V'maxFRC throughout the first year of life were derived for the infant cohort as a whole and also for subgroups of infants, based on parental asthma and smoking history. We conclude that lung function during the first year of life differs between genders and is adversely affected by in utero passive tobacco smoke exposure. Gender-specific predictive equations for V'maxFRG should be used during infancy. Pediatr Pulmonol. 2000; 29:331-340, (C) 2000 Wiley-Liss, Inc.	56	80	2000	10	10.1002/(SICI)1099-0496(200005)29:5<331::AID-PPUL1>3.0.CO;2-A	Pediatrics; Respiratory System
"Clinical Phenotypes of COPD: Identification, Definition and Implications for Guidelines. The term phenotype in the field of COPD is defined as ""a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes"". Among all phenotypes described, there are three that are associated with prognosis and especially are associated with a different response to currently available therapies. There phenotypes are: the exacerbator, the overlap COPD-asthma and the emphysema-hyperinflation. The exacerbator is characterised by the presence of, at least, two exacerbations the previous year, and on top of long-acting bronchodilators, may require the use of antiinflammatory drugs. The overlap phenotype presents symptoms of increased variability of airflow and incompletely reversible airflow obstruction. Due to the underlying inflammatory profile, it uses to have a good therapeutic response to inhaled corticosteroids in addition to bronchodilators. Lastly, the emphysema phenotype presents a poor therapeutic response to the existing antiinflammatory drugs and long-acting bronchodilators together with rehabilitation are the treatments of choice. Identifying the peculiarities of the different phenotypes of COPD will allow us to implement a more personalised treatment, in which the characteristics of the patients, together with their severity will be key to choose the best treatment option. (c) 2011 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.. copd| phenotype| asthma| emphysema| exacerbation| treatment|obstructive pulmonary-disease| inhaled corticosteroid treatment| resolution computed-tomography| randomized controlled-trial| volume reduction surgery| lung-function decline| air-flow obstruction| quality-of-life| dynamic hyperinflation| risk-factors."	MAR-2012	copd| phenotype| asthma| emphysema| exacerbation| treatment|obstructive pulmonary-disease| inhaled corticosteroid treatment| resolution computed-tomography| randomized controlled-trial| volume reduction surgery| lung-function decline| air-flow obstruction| quality-of-life| dynamic hyperinflation| risk-factors	Miravitlles, M; Calle, M; Soler-Cataluna, JJ	Clinical Phenotypes of COPD: Identification, Definition and Implications for Guidelines		ARCHIVOS DE BRONCONEUMOLOGIA	COPD; Phenotype; Asthma; Emphysema; Exacerbation; Treatment	OBSTRUCTIVE PULMONARY-DISEASE; INHALED CORTICOSTEROID TREATMENT; RESOLUTION COMPUTED-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; VOLUME REDUCTION SURGERY; LUNG-FUNCTION DECLINE; AIR-FLOW OBSTRUCTION; QUALITY-OF-LIFE; DYNAMIC HYPERINFLATION; RISK-FACTORS	"The term phenotype in the field of COPD is defined as ""a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes"". Among all phenotypes described, there are three that are associated with prognosis and especially are associated with a different response to currently available therapies. There phenotypes are: the exacerbator, the overlap COPD-asthma and the emphysema-hyperinflation. The exacerbator is characterised by the presence of, at least, two exacerbations the previous year, and on top of long-acting bronchodilators, may require the use of antiinflammatory drugs. The overlap phenotype presents symptoms of increased variability of airflow and incompletely reversible airflow obstruction. Due to the underlying inflammatory profile, it uses to have a good therapeutic response to inhaled corticosteroids in addition to bronchodilators. Lastly, the emphysema phenotype presents a poor therapeutic response to the existing antiinflammatory drugs and long-acting bronchodilators together with rehabilitation are the treatments of choice. Identifying the peculiarities of the different phenotypes of COPD will allow us to implement a more personalised treatment, in which the characteristics of the patients, together with their severity will be key to choose the best treatment option. (c) 2011 SEPAR. Published by Elsevier Espana, S.L. All rights reserved."	155	79	2012	13	10.1016/j.arbres.2011.10.007	Respiratory System
Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona. Background: The association between vitamin D status at birth and childhood allergic outcomes is uncertain. The desert climate of Tucson offers a unique setting for studying the health effects of higher exposure to vitamin D. Objective: To assess the relationship between cord blood 25-hydroxyvitamin D (25[OH]D) levels and allergic outcomes through age 5 years. Methods: Cord blood 25(OH)D levels were measured in 219 participants in the Tucson Infant Immune Study, a population-based birth cohort. Plasma total IgE and specific IgE levels to 6 aeroallergens were measured at 1, 2, 3, and 5 years. Skin prick test (SPT) positivity (wheal diameter >= 3 mm) and physician-diagnosed active allergic rhinitis and asthma were assessed at age 5 years. Longitudinal models were used to assess the relationship between 25(OH)D and IgE levels. Logistic regression models were used to assess the relationship of 25(OH)D level with SPT positivity, allergic rhinitis, and asthma. Results: The median cord blood 25(OH)D level was 64 nmol/L (interquartile range, 49-81 nmol/L). Relative to the reference group (50-74.9 nmol/L), both low (<50 nmol/L) and high (>= 100 nmol/L) levels were associated with increased total IgE (coefficient = 0.27, P = .006 and coefficient = 0.27, P = .04, respectively) and detectable inhalant allergen-specific IgE (odds ratio = 2.4, P = .03 and odds ratio = 4.0, P = .01, respectively) through age 5 years. High 25(OH)D levels were also associated with increased SPT positivity (odds ratio = 4.0, P = .02). By contrast, the 25(OH)D level was not significantly associated with allergic rhinitis or asthma. Conclusion: Both low and high levels of cord blood 25(OH)D were associated with increased aeroallergen sensitization. The association between vitamin D status and actual allergic diseases merits further study. (J Allergy Clin Immunol 2011;128:1093-9.). vitamin d| ige| aeroallergen| allergic rhinitis| asthma| children|vitamin-d intake| childhood asthma| allergic rhinitis| d supplementation| pregnancy| diseases| risk| ige| deficiency| infants.	NOV-2011	vitamin d| ige| aeroallergen| allergic rhinitis| asthma| children|vitamin-d intake| childhood asthma| allergic rhinitis| d supplementation| pregnancy| diseases| risk| ige| deficiency| infants	Rothers, J; Wright, AL; Stern, DA; Halonen, M; Camargo, CA	Cord blood 25-hydroxyvitamin D levels are associated with aeroallergen sensitization in children from Tucson, Arizona		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Vitamin D; IgE; aeroallergen; allergic rhinitis; asthma; children	VITAMIN-D INTAKE; CHILDHOOD ASTHMA; ALLERGIC RHINITIS; D SUPPLEMENTATION; PREGNANCY; DISEASES; RISK; IGE; DEFICIENCY; INFANTS	Background: The association between vitamin D status at birth and childhood allergic outcomes is uncertain. The desert climate of Tucson offers a unique setting for studying the health effects of higher exposure to vitamin D. Objective: To assess the relationship between cord blood 25-hydroxyvitamin D (25[OH]D) levels and allergic outcomes through age 5 years. Methods: Cord blood 25(OH)D levels were measured in 219 participants in the Tucson Infant Immune Study, a population-based birth cohort. Plasma total IgE and specific IgE levels to 6 aeroallergens were measured at 1, 2, 3, and 5 years. Skin prick test (SPT) positivity (wheal diameter >= 3 mm) and physician-diagnosed active allergic rhinitis and asthma were assessed at age 5 years. Longitudinal models were used to assess the relationship between 25(OH)D and IgE levels. Logistic regression models were used to assess the relationship of 25(OH)D level with SPT positivity, allergic rhinitis, and asthma. Results: The median cord blood 25(OH)D level was 64 nmol/L (interquartile range, 49-81 nmol/L). Relative to the reference group (50-74.9 nmol/L), both low (<50 nmol/L) and high (>= 100 nmol/L) levels were associated with increased total IgE (coefficient = 0.27, P = .006 and coefficient = 0.27, P = .04, respectively) and detectable inhalant allergen-specific IgE (odds ratio = 2.4, P = .03 and odds ratio = 4.0, P = .01, respectively) through age 5 years. High 25(OH)D levels were also associated with increased SPT positivity (odds ratio = 4.0, P = .02). By contrast, the 25(OH)D level was not significantly associated with allergic rhinitis or asthma. Conclusion: Both low and high levels of cord blood 25(OH)D were associated with increased aeroallergen sensitization. The association between vitamin D status and actual allergic diseases merits further study. (J Allergy Clin Immunol 2011;128:1093-9.)	33	79	2011	12	10.1016/j.jaci.2011.07.015	Allergy; Immunology
The host selects mucosal and luminal associations of coevolved gut microorganisms: a novel concept. Along the human gastrointestinal tract, microorganisms are confronted with multiple barriers. Besides selective physical conditions, the epithelium is regularly replaced and covered with a protective mucus layer trapping immune molecules. Recent insights into host defense strategies show that the host selects the intestinal microbiota, particularly the mucosa-associated microbial community. In this context, humans coevolved with thousands of intestinal microbial species that have adapted to provide host benefits, while avoiding pathogenic behavior that might destabilize their host interaction. While mucosal microorganisms would be crucial for immunological priming, luminal microorganisms would be important for nutrient digestion. Further, we propose that the intestinal microorganisms also coevolved with each other, leading to coherently organized, resilient microbial associations. During disturbances, functionally redundant members become more abundant and are crucial for preserving community functionality. The outside of the mucus layer, where host defense molecules are more diluted, could serve as an environment where microorganisms are protected from disturbances in the lumen and from where they can recolonize the lumen after perturbations. This might explain the remarkable temporal stability of microbial communities. Finally, commensals that become renegade or a decreased exposure to essential coevolved microorganisms may cause particular health problems such as inflammatory bowel diseases, obesity or allergies.. microbial communities| colon| symbiotic bacteria| crohn's disease| gastrointestinal|human intestinal microbiota| inflammatory-bowel-disease| innate immune-system| 16s ribosomal-rna| gradient gel-electrophoresis| butyrate-producing bacteria| lactobacillus-rhamnosus gg| ileal crohns-disease| toll-like receptor-3| t-cell polarization.	JUL-2011	microbial communities| colon| symbiotic bacteria| crohn's disease| gastrointestinal|human intestinal microbiota| inflammatory-bowel-disease| innate immune-system| 16s ribosomal-rna| gradient gel-electrophoresis| butyrate-producing bacteria| lactobacillus-rhamnosus gg| ileal crohns-disease| toll-like receptor-3| t-cell polarization	Van den Abbeele, P; Van de Wiele, T; Verstraete, W; Possemiers, S	The host selects mucosal and luminal associations of coevolved gut microorganisms: a novel concept		FEMS MICROBIOLOGY REVIEWS	microbial communities; colon; symbiotic bacteria; Crohn's disease; gastrointestinal	HUMAN INTESTINAL MICROBIOTA; INFLAMMATORY-BOWEL-DISEASE; INNATE IMMUNE-SYSTEM; 16S RIBOSOMAL-RNA; GRADIENT GEL-ELECTROPHORESIS; BUTYRATE-PRODUCING BACTERIA; LACTOBACILLUS-RHAMNOSUS GG; ILEAL CROHNS-DISEASE; TOLL-LIKE RECEPTOR-3; T-CELL POLARIZATION	Along the human gastrointestinal tract, microorganisms are confronted with multiple barriers. Besides selective physical conditions, the epithelium is regularly replaced and covered with a protective mucus layer trapping immune molecules. Recent insights into host defense strategies show that the host selects the intestinal microbiota, particularly the mucosa-associated microbial community. In this context, humans coevolved with thousands of intestinal microbial species that have adapted to provide host benefits, while avoiding pathogenic behavior that might destabilize their host interaction. While mucosal microorganisms would be crucial for immunological priming, luminal microorganisms would be important for nutrient digestion. Further, we propose that the intestinal microorganisms also coevolved with each other, leading to coherently organized, resilient microbial associations. During disturbances, functionally redundant members become more abundant and are crucial for preserving community functionality. The outside of the mucus layer, where host defense molecules are more diluted, could serve as an environment where microorganisms are protected from disturbances in the lumen and from where they can recolonize the lumen after perturbations. This might explain the remarkable temporal stability of microbial communities. Finally, commensals that become renegade or a decreased exposure to essential coevolved microorganisms may cause particular health problems such as inflammatory bowel diseases, obesity or allergies.	209	79	2011	24	10.1111/j.1574-6976.2011.00270.x	Microbiology
Acute effects of air pollution on pediatric asthma exacerbation: Evidence of association and effect modification. We investigated the short-term effects of particulate matter with aerodynamic diameter < 10 mu g/m(3) (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O-3) on pediatric asthma emergency admissions in Athens, Greece over the period 2001-2004. We explored effect modification patterns by season, sex, age and by the presence of desert dust transported mainly from the Sahara area. We used daily time-series data provided by the children's hospitals and the fixed monitoring stations. The associations were investigated using Poisson regression models controlling for seasonality, weather, influenza episodes, day of the week and holiday effects. A 10 mu g/m(3) increase in PM10, was associated with a 2.54% increase (95% confidence interval (Cl): 0.06%, 5.08%) in the number of pediatric asthma hospital admissions, while the same increase in SO2 was associated with a 5.98% (95% Cl: 0.88%, 11.33%) increase. O-3 was associated with a statistically significant increase in asthma admissions among older children in the summer. Our findings provide limited evidence of an association between NO2 exposure and asthma exacerbation. Statistically significant PM10 effects were higher during winter and during desert dust days, while SO2 effects occurred mainly during spring. Our study confirms previously reported PM10 effects on emergency hospital admissions for pediatric asthma and further provides evidence of stronger effects during desert dust days. We additionally report severe effects of SO2, even at today's low concentration levels. (C) 2011 Elsevier Inc. All rights reserved.. air pollution| asthma| children| desert dust| time-series|4 european cities| time-series| emergency admissions| case-crossover| children| exposure| visits| health| mortality| project.	APR-2011	air pollution| asthma| children| desert dust| time-series|4 european cities| time-series| emergency admissions| case-crossover| children| exposure| visits| health| mortality| project	Samoli, E; Nastos, PT; Paliatsos, AG; Katsouyanni, K; Priftis, KN	Acute effects of air pollution on pediatric asthma exacerbation: Evidence of association and effect modification		ENVIRONMENTAL RESEARCH	Air pollution; Asthma; Children; Desert dust; Time-series	4 EUROPEAN CITIES; TIME-SERIES; EMERGENCY ADMISSIONS; CASE-CROSSOVER; CHILDREN; EXPOSURE; VISITS; HEALTH; MORTALITY; PROJECT	We investigated the short-term effects of particulate matter with aerodynamic diameter < 10 mu g/m(3) (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O-3) on pediatric asthma emergency admissions in Athens, Greece over the period 2001-2004. We explored effect modification patterns by season, sex, age and by the presence of desert dust transported mainly from the Sahara area. We used daily time-series data provided by the children's hospitals and the fixed monitoring stations. The associations were investigated using Poisson regression models controlling for seasonality, weather, influenza episodes, day of the week and holiday effects. A 10 mu g/m(3) increase in PM10, was associated with a 2.54% increase (95% confidence interval (Cl): 0.06%, 5.08%) in the number of pediatric asthma hospital admissions, while the same increase in SO2 was associated with a 5.98% (95% Cl: 0.88%, 11.33%) increase. O-3 was associated with a statistically significant increase in asthma admissions among older children in the summer. Our findings provide limited evidence of an association between NO2 exposure and asthma exacerbation. Statistically significant PM10 effects were higher during winter and during desert dust days, while SO2 effects occurred mainly during spring. Our study confirms previously reported PM10 effects on emergency hospital admissions for pediatric asthma and further provides evidence of stronger effects during desert dust days. We additionally report severe effects of SO2, even at today's low concentration levels. (C) 2011 Elsevier Inc. All rights reserved.	42	79	2011	7	10.1016/j.envres.2011.01.014	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
"Personal Exposures to Traffic-Related Air Pollution and Acute Respiratory Health among Bronx Schoolchildren with Asthma. BACKGROUND: Previous studies have reported relationships between adverse respiratory health outcomes and residential proximity to traffic pollution, but have not shown this at a personal exposure level. OBJECTIVE: We compared, among inner-city children with asthma, the associations of adverse asthma outcome incidences with increased personal exposure to particulate matter mass <= 2.5 mu m in aerodynamic diameter (PM2.5) air pollution versus the diesel-related carbonaceous fraction of PM2.5. METHODS: Daily 24-hr personal samples of PM2.5, including the elemental carbon (EC) fraction, were collected for 40 fifth-grade children with asthma at four South Bronx schools (10 children per school) during approximately 1 month each. Spirometry and symptom scores were recorded several times daily during weekdays. RESULTS: We found elevated same-day relative risks of wheeze [1.45; 95% confidence interval (CI), 1.03-2.04)], shortness of breath (1.41; 95% CI, 1.01-1.99), and total symptoms (1.30; 95% CI, 1.04-1.62) with an increase in personal EC, but not with personal PM2.5 mass. We found increased risk of cough, wheeze, and total symptoms with increased 1-day lag and 2-day average personal and school-site EC. We found no significant associations with school-site PM2.5 mass or sulfur. The EC effect estimate was robust to addition of gaseous pollutants. CONCLUSION: Adverse health associations were strongest with personal measures of EC exposure, suggesting that the diesel ""soot"" fraction of PM2.5 is most responsible for pollution-related asthma exacerbations among children living near roadways. Studies that rely on exposure to PM mass may underestimate PM health impacts.. pollution| asthma| children's health| diesel| elemental carbon| personal monitoring traffic| pm2.5|exhaled nitric-oxide| lung-function| childhood asthma| south bronx| children| association| particulate| symptoms| inflammation| communities."	APR-2011	pollution| asthma| children's health| diesel| elemental carbon| personal monitoring traffic| pm2.5|exhaled nitric-oxide| lung-function| childhood asthma| south bronx| children| association| particulate| symptoms| inflammation| communities	Spira-Cohen, A; Chen, LC; Kendall, M; Lall, R; Thurston, GD	Personal Exposures to Traffic-Related Air Pollution and Acute Respiratory Health among Bronx Schoolchildren with Asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	pollution; asthma; children's health; diesel; elemental carbon; personal monitoring traffic; PM2.5	EXHALED NITRIC-OXIDE; LUNG-FUNCTION; CHILDHOOD ASTHMA; SOUTH BRONX; CHILDREN; ASSOCIATION; PARTICULATE; SYMPTOMS; INFLAMMATION; COMMUNITIES	"BACKGROUND: Previous studies have reported relationships between adverse respiratory health outcomes and residential proximity to traffic pollution, but have not shown this at a personal exposure level. OBJECTIVE: We compared, among inner-city children with asthma, the associations of adverse asthma outcome incidences with increased personal exposure to particulate matter mass <= 2.5 mu m in aerodynamic diameter (PM2.5) air pollution versus the diesel-related carbonaceous fraction of PM2.5. METHODS: Daily 24-hr personal samples of PM2.5, including the elemental carbon (EC) fraction, were collected for 40 fifth-grade children with asthma at four South Bronx schools (10 children per school) during approximately 1 month each. Spirometry and symptom scores were recorded several times daily during weekdays. RESULTS: We found elevated same-day relative risks of wheeze [1.45; 95% confidence interval (CI), 1.03-2.04)], shortness of breath (1.41; 95% CI, 1.01-1.99), and total symptoms (1.30; 95% CI, 1.04-1.62) with an increase in personal EC, but not with personal PM2.5 mass. We found increased risk of cough, wheeze, and total symptoms with increased 1-day lag and 2-day average personal and school-site EC. We found no significant associations with school-site PM2.5 mass or sulfur. The EC effect estimate was robust to addition of gaseous pollutants. CONCLUSION: Adverse health associations were strongest with personal measures of EC exposure, suggesting that the diesel ""soot"" fraction of PM2.5 is most responsible for pollution-related asthma exacerbations among children living near roadways. Studies that rely on exposure to PM mass may underestimate PM health impacts."	47	79	2011	7	10.1289/ehp.1002653	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Projections of the effects of climate change on allergic asthma: the contribution of aerobiology. Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by urban air pollutants interacting directly with pollen. Data suggest an increasing effect of aeroallergens on allergic patients over this period, which may also imply a greater likelihood of the development of an allergic respiratory disease in sensitized subjects and exacerbation of symptomatic patients. There are a number of limitations that make predictions uncertain, and further and specifically designed studies are needed to clarify current effects and future scenarios. We recommend: More stress on pollen/spore exposure in the diagnosis and treatment guidelines of respiratory and allergic diseases; collection of aerobiological data in a structured way at the European level; creation, promotion and support of multidisciplinary research teams in this area; lobbying the European Union and other funders to finance this research.. allergic diseases| climate change| environment| pollen| spores|ragweed ambrosia-artemisiifolia| elevated atmospheric co2| thunderstorm-associated asthma| long-range transport| grass-pollen seasons| common ragweed| birch pollen| environmental-factors| diesel exhaust| air-pollution.	SEP-2010	allergic diseases| climate change| environment| pollen| spores|ragweed ambrosia-artemisiifolia| elevated atmospheric co2| thunderstorm-associated asthma| long-range transport| grass-pollen seasons| common ragweed| birch pollen| environmental-factors| diesel exhaust| air-pollution	Cecchi, L; D'Amato, G; Ayres, JG; Galan, C; Forastiere, F; Forsberg, B; Gerritsen, J; Nunes, C; Behrendt, H; Akdis, C; Dahl, R; Annesi-Maesano, I	Projections of the effects of climate change on allergic asthma: the contribution of aerobiology		ALLERGY	allergic diseases; climate change; environment; pollen; spores	RAGWEED AMBROSIA-ARTEMISIIFOLIA; ELEVATED ATMOSPHERIC CO2; THUNDERSTORM-ASSOCIATED ASTHMA; LONG-RANGE TRANSPORT; GRASS-POLLEN SEASONS; COMMON RAGWEED; BIRCH POLLEN; ENVIRONMENTAL-FACTORS; DIESEL EXHAUST; AIR-POLLUTION	Climate change is unequivocal and represents a possible threat for patients affected by allergic conditions. It has already had an impact on living organisms, including plants and fungi with current scenarios projecting further effects by the end of the century. Over the last three decades, studies have shown changes in production, dispersion and allergen content of pollen and spores, which may be region- and species-specific. In addition, these changes may have been influenced by urban air pollutants interacting directly with pollen. Data suggest an increasing effect of aeroallergens on allergic patients over this period, which may also imply a greater likelihood of the development of an allergic respiratory disease in sensitized subjects and exacerbation of symptomatic patients. There are a number of limitations that make predictions uncertain, and further and specifically designed studies are needed to clarify current effects and future scenarios. We recommend: More stress on pollen/spore exposure in the diagnosis and treatment guidelines of respiratory and allergic diseases; collection of aerobiological data in a structured way at the European level; creation, promotion and support of multidisciplinary research teams in this area; lobbying the European Union and other funders to finance this research.	99	79	2010	9	10.1111/j.1398-9995.2010.02423.x	Allergy; Immunology
"Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children. Epidemiologic data suggest that the incidence of food allergy (FA) is increasing among children, yet a satisfactory model of its pathogenesis remains elusive. FA is the consequence of maladaptive immune responses to common and otherwise innocuous food antigens. Concurrent with the increase in FA is an epidemic of vitamin D deficiency (VDD) caused by several factors, especially decreased sunlight/UVB exposure. There is growing appreciation of the importance of the pleiotropic hormone vitamin D in the development of tolerance, immune system defenses, and epithelial barrier integrity. We propose a ""multiplehit'' model in which VDD in a developmentally critical period increases susceptibility to colonization with abnormal intestinal microbial flora and gastrointestinal infections, contributing to abnormal intestinal barrier permeability and excess and inappropriate exposure of the immune system to dietary allergens. A compounding effect (and additional ""hit'') of VDD is the promotion of a pro-sensitization immune imbalance that might compromise immunologic tolerance and contribute to FA. We propose that early correction of VDD might promote mucosal immunity, healthy microbial ecology, and allergen tolerance and thereby blunt the FA epidemic in children. (J Allergy Clin Immunol 2010;126:217-22.). food allergy| vitamin d| vitamin d deficiency| mucosal immunity| epithelial barrier| microbial ecology| infections| sensitization| atopy|regulatory t-cells| body-mass index| d deficiency| atopic-dermatitis| 1,25-dihydroxyvitamin d-3| united-states| oral tolerance| immune-system| us children| d-receptor."	AUG-2010	food allergy| vitamin d| vitamin d deficiency| mucosal immunity| epithelial barrier| microbial ecology| infections| sensitization| atopy|regulatory t-cells| body-mass index| d deficiency| atopic-dermatitis| 1,25-dihydroxyvitamin d-3| united-states| oral tolerance| immune-system| us children| d-receptor	Vassallo, MF; Camargo, CA	Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Food allergy; vitamin D; vitamin D deficiency; mucosal immunity; epithelial barrier; microbial ecology; infections; sensitization; atopy	REGULATORY T-CELLS; BODY-MASS INDEX; D DEFICIENCY; ATOPIC-DERMATITIS; 1,25-DIHYDROXYVITAMIN D-3; UNITED-STATES; ORAL TOLERANCE; IMMUNE-SYSTEM; US CHILDREN; D-RECEPTOR	"Epidemiologic data suggest that the incidence of food allergy (FA) is increasing among children, yet a satisfactory model of its pathogenesis remains elusive. FA is the consequence of maladaptive immune responses to common and otherwise innocuous food antigens. Concurrent with the increase in FA is an epidemic of vitamin D deficiency (VDD) caused by several factors, especially decreased sunlight/UVB exposure. There is growing appreciation of the importance of the pleiotropic hormone vitamin D in the development of tolerance, immune system defenses, and epithelial barrier integrity. We propose a ""multiplehit'' model in which VDD in a developmentally critical period increases susceptibility to colonization with abnormal intestinal microbial flora and gastrointestinal infections, contributing to abnormal intestinal barrier permeability and excess and inappropriate exposure of the immune system to dietary allergens. A compounding effect (and additional ""hit'') of VDD is the promotion of a pro-sensitization immune imbalance that might compromise immunologic tolerance and contribute to FA. We propose that early correction of VDD might promote mucosal immunity, healthy microbial ecology, and allergen tolerance and thereby blunt the FA epidemic in children. (J Allergy Clin Immunol 2010;126:217-22.)"	67	79	2010	6	10.1016/j.jaci.2010.06.011	Allergy; Immunology
Update on mechanisms of allergen injection immunotherapy. The incidence of allergic diseases is increasing at an alarming rate, paricularly in countries with a western lifestyle. Currently in the UK, approximately one quarter of the population suffers from seasonal allergic rhinitis. Most patients can be treated with conventional pharmacotherapy on an 'as needed' symptomatic basis whereas allergen immunotherapy represents a useful treatment approach in carefully selected patients with severe, IgE-mediated disease. Allergen immunotherapy can deliver improvements in hayfever symptoms over and above that which can be achieved by pharmacotherapy. In addition, unlike pharmacotherapy, allergen immunotherapy provides long-term clinical benefits. These include long-term disease remission, prevention of new atopic sensitisations and a reduction in disease progression from rhinitis to asthma. This review provides a comprehensive update on the mechanisms of allergen injection immunotherapy, recent data on the mechanisms of sublingual allergen immunotherapy is also included.. grass-pollen immunotherapy| regulatory t-cells| messenger-rna expression| placebo-controlled trial| affinity ige receptor| plasmacytoid dendritic cells| randomized controlled-trial| phase skin reactions| house-dust mite| sublingual immunotherapy.	JUL-2008	grass-pollen immunotherapy| regulatory t-cells| messenger-rna expression| placebo-controlled trial| affinity ige receptor| plasmacytoid dendritic cells| randomized controlled-trial| phase skin reactions| house-dust mite| sublingual immunotherapy	James, LK; Durham, SR	Update on mechanisms of allergen injection immunotherapy		CLINICAL AND EXPERIMENTAL ALLERGY		GRASS-POLLEN IMMUNOTHERAPY; REGULATORY T-CELLS; MESSENGER-RNA EXPRESSION; PLACEBO-CONTROLLED TRIAL; AFFINITY IGE RECEPTOR; PLASMACYTOID DENDRITIC CELLS; RANDOMIZED CONTROLLED-TRIAL; PHASE SKIN REACTIONS; HOUSE-DUST MITE; SUBLINGUAL IMMUNOTHERAPY	The incidence of allergic diseases is increasing at an alarming rate, paricularly in countries with a western lifestyle. Currently in the UK, approximately one quarter of the population suffers from seasonal allergic rhinitis. Most patients can be treated with conventional pharmacotherapy on an 'as needed' symptomatic basis whereas allergen immunotherapy represents a useful treatment approach in carefully selected patients with severe, IgE-mediated disease. Allergen immunotherapy can deliver improvements in hayfever symptoms over and above that which can be achieved by pharmacotherapy. In addition, unlike pharmacotherapy, allergen immunotherapy provides long-term clinical benefits. These include long-term disease remission, prevention of new atopic sensitisations and a reduction in disease progression from rhinitis to asthma. This review provides a comprehensive update on the mechanisms of allergen injection immunotherapy, recent data on the mechanisms of sublingual allergen immunotherapy is also included.	167	79	2008	15	10.1111/j.1365-2222.2008.02976.x	Allergy; Immunology
Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model. Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers decreased AHR in a murine model of asthma. To elucidate the mechanisms for the beneficial effects of beta-blockers, we examined the effects of chronic administration of several beta-adrenoceptor ligands in a murine model of allergic asthma. Administration of beta-blockers resulted in a reduction in total cell counts, eosinophils, and the cytokines IL-13, IL-10, IL-5, and TGF-beta 1 in bronchoalveolar lavage, and attenuated epithelial mucin content and morphologic changes. The differences in mucin content also occurred if the beta-blockers were administered only during the ovalbumin challenge phase, but administration of beta-blockers for 7 days was not as effective as administration for 28 days. These results indicate that in a murine model of asthma, chronic administration of beta-blockers reduces inflammation and mucous metaplasia, cardinal features of asthma that may contribute to airflow obstruction and AHR. Similar to heart failure, our results provide a second disease model in which beta-blockers producing an acutely detrimental effect may provide a therapeutically beneficial effect with chronic administration.. beta-blockers| beta-adrenoceptor| asthma| mucin| airway inflammation|heart-failure| adrenergic-blockade| airway mucus| goblet cell| overexpression| abnormalities| expression| bucindolol| secretion| mice.	MAR-2008	beta-blockers| beta-adrenoceptor| asthma| mucin| airway inflammation|heart-failure| adrenergic-blockade| airway mucus| goblet cell| overexpression| abnormalities| expression| bucindolol| secretion| mice	Nguyen, LP; Omoluabi, O; Parra, S; Frieske, JM; Clement, C; Ammar-Aouchiche, Z; Ho, SB; Ehre, C; Kesimer, M; Knoll, BJ; Tuvim, MJ; Dickey, BF; Bond, RA	Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	beta-blockers; beta-adrenoceptor; asthma; mucin; airway inflammation	HEART-FAILURE; ADRENERGIC-BLOCKADE; AIRWAY MUCUS; GOBLET CELL; OVEREXPRESSION; ABNORMALITIES; EXPRESSION; BUCINDOLOL; SECRETION; MICE	Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers decreased AHR in a murine model of asthma. To elucidate the mechanisms for the beneficial effects of beta-blockers, we examined the effects of chronic administration of several beta-adrenoceptor ligands in a murine model of allergic asthma. Administration of beta-blockers resulted in a reduction in total cell counts, eosinophils, and the cytokines IL-13, IL-10, IL-5, and TGF-beta 1 in bronchoalveolar lavage, and attenuated epithelial mucin content and morphologic changes. The differences in mucin content also occurred if the beta-blockers were administered only during the ovalbumin challenge phase, but administration of beta-blockers for 7 days was not as effective as administration for 28 days. These results indicate that in a murine model of asthma, chronic administration of beta-blockers reduces inflammation and mucous metaplasia, cardinal features of asthma that may contribute to airflow obstruction and AHR. Similar to heart failure, our results provide a second disease model in which beta-blockers producing an acutely detrimental effect may provide a therapeutically beneficial effect with chronic administration.	34	79	2008	7	10.1165/rcmb.2007-0279RC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Current state of the science: Health effects and indoor environmental quality. Our understanding of the relationship between human health and the indoor environment continues to evolve. Previous research on health and indoor environments has tended to concentrate on discrete pollutant sources and exposures and on specific disease processes. Recently, efforts have been made to characterize more fully the complex interactions between the health of occupants and the interior spaces they inhabit. In this article we review recent advances in source characterization, exposure assessment, health effects associated with indoor exposures, and intervention research related to indoor environments. Advances in source characterization include a better understanding of how chemicals are transported and processed within spaces and the role that other factors such as lighting and building design may play in determining health. Efforts are under way to improve our ability to measure exposures, but this remains a challenge, particularly for biological agents. Researchers are also examining the effects of multiple exposures as well as the effects of exposures on vulnerable populations such as children and the elderly. In addition, a number of investigators are also studying the effects of modifying building design, materials, and operations on occupant health. Identification of research priorities should include input from building designers, operators, and the public health community.. allergens| chemistry| exposure| fungi| humans| indoor air pollution| intervention| review|volatile organic-compounds| assessment methodology pteam| airborne particulate matter| polymerase-chain-reaction| hazardous air-pollutants| water-damaged buildings| heart-rate-variability| of-the-literature| stachybotrys-chartarum| time-series.	JUN-2007	allergens| chemistry| exposure| fungi| humans| indoor air pollution| intervention| review|volatile organic-compounds| assessment methodology pteam| airborne particulate matter| polymerase-chain-reaction| hazardous air-pollutants| water-damaged buildings| heart-rate-variability| of-the-literature| stachybotrys-chartarum| time-series	Mitchell, CS; Zhang, JFJ; Sigsgaard, T; Jantunen, M; Lioy, PJ; Samson, R; Karol, MH	Current state of the science: Health effects and indoor environmental quality		ENVIRONMENTAL HEALTH PERSPECTIVES	allergens; chemistry; exposure; fungi; humans; indoor air pollution; intervention; review	VOLATILE ORGANIC-COMPOUNDS; ASSESSMENT METHODOLOGY PTEAM; AIRBORNE PARTICULATE MATTER; POLYMERASE-CHAIN-REACTION; HAZARDOUS AIR-POLLUTANTS; WATER-DAMAGED BUILDINGS; HEART-RATE-VARIABILITY; OF-THE-LITERATURE; STACHYBOTRYS-CHARTARUM; TIME-SERIES	Our understanding of the relationship between human health and the indoor environment continues to evolve. Previous research on health and indoor environments has tended to concentrate on discrete pollutant sources and exposures and on specific disease processes. Recently, efforts have been made to characterize more fully the complex interactions between the health of occupants and the interior spaces they inhabit. In this article we review recent advances in source characterization, exposure assessment, health effects associated with indoor exposures, and intervention research related to indoor environments. Advances in source characterization include a better understanding of how chemicals are transported and processed within spaces and the role that other factors such as lighting and building design may play in determining health. Efforts are under way to improve our ability to measure exposures, but this remains a challenge, particularly for biological agents. Researchers are also examining the effects of multiple exposures as well as the effects of exposures on vulnerable populations such as children and the elderly. In addition, a number of investigators are also studying the effects of modifying building design, materials, and operations on occupant health. Identification of research priorities should include input from building designers, operators, and the public health community.	109	79	2007	7	10.1289/ehp.8987	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
"The sinus, allergy and migraine study (SAMS). Objective.-The objective of this study is to classify (according to the current International Headache Society's criteria [ICHD-II]) the headache types that those with self-diagnosed sinus headache experience and to determine barriers to correct diagnosis. Background.-The American Migraine Study II estimates that 28 million Americans suffer from migraine headache. The majority of these patients remain undiagnosed and many are erroneously diagnosed as having sinus headache. Despite this common diagnosis, the concept of sinus headache remains an enigma with a relative paucity of information in the literature. Methods.-Advertising in the greater Phoenix, U.S. metropolitan area was used to recruit 100 willing and consecutive subjects to participate in this descriptive clinical study (The Sinus, Allergy and Migraine Study [SAMS]). All patients who believed they suffered from sinus headache and were over 18 years of age were enrolled without exclusion. A detailed history and exam was performed in each patient, and patients were given headache diagnoses based on the current International Headache Society's (IHS) criteria. Results.-Of the 100 subjects with self-diagnosed headache, IHS diagnoses mistaken as sinus headache included migraine with or without aura (52%), chronic migraine associated with medication overuse versus probable medication overuse headache (11%), probable migraine (23%), cluster headache (1%), hemicrania continua (1%), headache secondary to rhinosinusitis (3%), and headaches nonclassifiable (9%). Weather changes (83%), seasonal variation (73%), exposure to allergens (62%), and changes in altitude (38%) were frequent migraine triggers. Seventy-six percent of migraine subjects reported pain in the distribution of the second division of the trigeminal nerve (either unilateral or bilateral), and 62% experienced bilateral forehead and maxillary pain with their headaches. The most common associated features included nasal congestion (56%), eyelid edema (37%), rhinorrhea (25%), conjunctival injection (22%), lacrimation (19%), and ptosis (3%). The headaches nonclassifiable were characterized by a bilateral maxillary pressure of mild to moderate intensity associated with at least one cranial autonomic symptom. Features suggestive of migraine were absent in all 9 of these nonclassifiable cases. Conclusions.-The majority of those with self-diagnosed sinus headache have migraine or probable migraine. In those patients with migraine, the most common reasons for misdiagnosis include headache triggers, pain location, and associated features (""guilt by provocation, location, and association"") commonly attributed to sinus headache. The clinician must be aware of these unique presentations of migraine so that a correct diagnosis can be made and effective treatment instituted. A portion of patients with self-diagnosed sinus headache suffer from a headache type, which is unclassifiable by the current IHS criteria. These headaches are characterized by bilateral maxillary pressure, mild to moderate pain intensity, cranial autonomic symptoms, and the complete absence of migraine features.. allergy| cranial autonomic symptoms| headache| migraine| sinus|prevalence| headache."	FEB-2007	allergy| cranial autonomic symptoms| headache| migraine| sinus|prevalence| headache	Eross, E; Dodick, D; Eross, M	The sinus, allergy and migraine study (SAMS)		HEADACHE	allergy; cranial autonomic symptoms; headache; migraine; sinus	PREVALENCE; HEADACHE	"Objective.-The objective of this study is to classify (according to the current International Headache Society's criteria [ICHD-II]) the headache types that those with self-diagnosed sinus headache experience and to determine barriers to correct diagnosis. Background.-The American Migraine Study II estimates that 28 million Americans suffer from migraine headache. The majority of these patients remain undiagnosed and many are erroneously diagnosed as having sinus headache. Despite this common diagnosis, the concept of sinus headache remains an enigma with a relative paucity of information in the literature. Methods.-Advertising in the greater Phoenix, U.S. metropolitan area was used to recruit 100 willing and consecutive subjects to participate in this descriptive clinical study (The Sinus, Allergy and Migraine Study [SAMS]). All patients who believed they suffered from sinus headache and were over 18 years of age were enrolled without exclusion. A detailed history and exam was performed in each patient, and patients were given headache diagnoses based on the current International Headache Society's (IHS) criteria. Results.-Of the 100 subjects with self-diagnosed headache, IHS diagnoses mistaken as sinus headache included migraine with or without aura (52%), chronic migraine associated with medication overuse versus probable medication overuse headache (11%), probable migraine (23%), cluster headache (1%), hemicrania continua (1%), headache secondary to rhinosinusitis (3%), and headaches nonclassifiable (9%). Weather changes (83%), seasonal variation (73%), exposure to allergens (62%), and changes in altitude (38%) were frequent migraine triggers. Seventy-six percent of migraine subjects reported pain in the distribution of the second division of the trigeminal nerve (either unilateral or bilateral), and 62% experienced bilateral forehead and maxillary pain with their headaches. The most common associated features included nasal congestion (56%), eyelid edema (37%), rhinorrhea (25%), conjunctival injection (22%), lacrimation (19%), and ptosis (3%). The headaches nonclassifiable were characterized by a bilateral maxillary pressure of mild to moderate intensity associated with at least one cranial autonomic symptom. Features suggestive of migraine were absent in all 9 of these nonclassifiable cases. Conclusions.-The majority of those with self-diagnosed sinus headache have migraine or probable migraine. In those patients with migraine, the most common reasons for misdiagnosis include headache triggers, pain location, and associated features (""guilt by provocation, location, and association"") commonly attributed to sinus headache. The clinician must be aware of these unique presentations of migraine so that a correct diagnosis can be made and effective treatment instituted. A portion of patients with self-diagnosed sinus headache suffer from a headache type, which is unclassifiable by the current IHS criteria. These headaches are characterized by bilateral maxillary pressure, mild to moderate pain intensity, cranial autonomic symptoms, and the complete absence of migraine features."	19	79	2007	12	10.1111/j.1526-4610.2006.00688.x	Neurosciences & Neurology
Mechanisms of allergen specific immunotherapy - T-cell tolerance and more. Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific T-regulatory (Treg) cells and T helper 2 cells appears to be decisive in the development of allergic and healthy immune response against allergens. Treg cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific T helper 2 cells in allergic individuals. A decrease in interleukin (IL)-4, IL-5 and IL-13 production by allergen-specific CD4(+) T cells due to the induction of peripheral T cell tolerance is the most essential step in allergen-specific immunotherapy (SIT). Suppressed proliferative and cytokine responses against the major allergens are induced by multiple suppressor factors, such as cytokines like IL-10 and transforming growth factor (TGF)-beta and cell surface molecules like cytotoxic T lymphocyte antigen-4, programmed death-1 and histamine receptor 2. There is considerable rationale for targeting T cells to increase efficacy of SIT. Such novel approaches include the use of modified allergens produced using recombinant DNA technology and adjuvants or additional drugs, which may increase the generation of allergen-specific peripheral tolerance. By the application of the recent knowledge in Treg cells and related mechanisms of peripheral tolerance, more rational and safer approaches are awaiting for the future of prevention and cure of allergic diseases.. allergy| histamine| immunoglobulins| specific immunotherapy| t-regulatory cells| tolerance|grass-pollen immunotherapy| immunological self-tolerance| eosinophil cationic protein| messenger-rna expression| house-dust mites| hay-fever| sublingual immunotherapy| asthmatic-children| in-vitro| venom immunotherapy.	JUL-2006	allergy| histamine| immunoglobulins| specific immunotherapy| t-regulatory cells| tolerance|grass-pollen immunotherapy| immunological self-tolerance| eosinophil cationic protein| messenger-rna expression| house-dust mites| hay-fever| sublingual immunotherapy| asthmatic-children| in-vitro| venom immunotherapy	Jutel, M; Akdis, M; Blaser, K; Akdis, CA	Mechanisms of allergen specific immunotherapy - T-cell tolerance and more		ALLERGY	allergy; histamine; immunoglobulins; specific immunotherapy; T-regulatory cells; tolerance	GRASS-POLLEN IMMUNOTHERAPY; IMMUNOLOGICAL SELF-TOLERANCE; EOSINOPHIL CATIONIC PROTEIN; MESSENGER-RNA EXPRESSION; HOUSE-DUST MITES; HAY-FEVER; SUBLINGUAL IMMUNOTHERAPY; ASTHMATIC-CHILDREN; IN-VITRO; VENOM IMMUNOTHERAPY	Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific T-regulatory (Treg) cells and T helper 2 cells appears to be decisive in the development of allergic and healthy immune response against allergens. Treg cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific T helper 2 cells in allergic individuals. A decrease in interleukin (IL)-4, IL-5 and IL-13 production by allergen-specific CD4(+) T cells due to the induction of peripheral T cell tolerance is the most essential step in allergen-specific immunotherapy (SIT). Suppressed proliferative and cytokine responses against the major allergens are induced by multiple suppressor factors, such as cytokines like IL-10 and transforming growth factor (TGF)-beta and cell surface molecules like cytotoxic T lymphocyte antigen-4, programmed death-1 and histamine receptor 2. There is considerable rationale for targeting T cells to increase efficacy of SIT. Such novel approaches include the use of modified allergens produced using recombinant DNA technology and adjuvants or additional drugs, which may increase the generation of allergen-specific peripheral tolerance. By the application of the recent knowledge in Treg cells and related mechanisms of peripheral tolerance, more rational and safer approaches are awaiting for the future of prevention and cure of allergic diseases.	132	79	2006	12	10.1111/j.1398-9995.2006.01175.x	Allergy; Immunology
Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis. Cysteinyl leukotrienes (CysLTs) are a family of inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages. This article reviews the data for the role of CysLTs as multi-functional mediators in allergic rhinitis (AR). We review the evidence that: (1) CysLTs are released from inflammatory cells that participate in AR, (2) receptors for CysLTs are located in nasal tissue, (3) CysLTs are increased in patients with AR and are released following allergen exposure, (4) administration of CysLTs reproduces the symptoms of AR, (5) CysLTs play roles in the maturation, as well as tissue recruitment, of inflammatory cells, and (6) a complex inter-regulation between CysLTs and a variety of other inflammatory mediators exists.. allergic rhinitis| cysteinyl leukotrienes| cyslt(1) receptor| eosinophils| inflammation| leukotriene c4 synthase| 5-lipoxygenase|colony-stimulating factor| human mast-cells| placebo-controlled trial| vein endothelial-cells| human nasal-mucosa| hematopoietic progenitor cells| arachidonic-acid metabolites| peripheral-blood leukocytes| gene disruption reveals| c-4 synthase expression.	JUN-2006	allergic rhinitis| cysteinyl leukotrienes| cyslt(1) receptor| eosinophils| inflammation| leukotriene c4 synthase| 5-lipoxygenase|colony-stimulating factor| human mast-cells| placebo-controlled trial| vein endothelial-cells| human nasal-mucosa| hematopoietic progenitor cells| arachidonic-acid metabolites| peripheral-blood leukocytes| gene disruption reveals| c-4 synthase expression	Peters-Golden, M; Gleason, MM; Togias, A	Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis		CLINICAL AND EXPERIMENTAL ALLERGY	allergic rhinitis; cysteinyl leukotrienes; CysLT(1) receptor; eosinophils; inflammation; leukotriene C4 synthase; 5-lipoxygenase	COLONY-STIMULATING FACTOR; HUMAN MAST-CELLS; PLACEBO-CONTROLLED TRIAL; VEIN ENDOTHELIAL-CELLS; HUMAN NASAL-MUCOSA; HEMATOPOIETIC PROGENITOR CELLS; ARACHIDONIC-ACID METABOLITES; PERIPHERAL-BLOOD LEUKOCYTES; GENE DISRUPTION REVEALS; C-4 SYNTHASE EXPRESSION	Cysteinyl leukotrienes (CysLTs) are a family of inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages. This article reviews the data for the role of CysLTs as multi-functional mediators in allergic rhinitis (AR). We review the evidence that: (1) CysLTs are released from inflammatory cells that participate in AR, (2) receptors for CysLTs are located in nasal tissue, (3) CysLTs are increased in patients with AR and are released following allergen exposure, (4) administration of CysLTs reproduces the symptoms of AR, (5) CysLTs play roles in the maturation, as well as tissue recruitment, of inflammatory cells, and (6) a complex inter-regulation between CysLTs and a variety of other inflammatory mediators exists.	202	79	2006	15	10.1111/j.1365-2222.2006.02498.x	Allergy; Immunology
Association between ventilation rates in 390 Swedish homes and allergic symptoms in children. The aim of the study was to test the hypothesis that a low-ventilation rate in homes is associated with an increased prevalence of asthma and allergic symptoms among children. A total of 198 cases (with at least two of three symptoms: wheezing, rhinitis, eczema) and 202 healthy controls, living in 390 homes, were examined by physicians. Ventilation rates were measured by a passive tracer gas method, and inspections were carried out in the homes. About 60% of the multi-family houses and about 80% of the single-family houses did not fulfill the minimum requirement regarding ventilation rate in the Swedish building code (0.5 air changes per hour, ach). Cases had significantly lower ventilation rates than controls and a dose-response relationship was indicated.. ventilation rate| homes| asthma| allergic symptoms| children|house-dust mite| atopic-dermatitis| young-children| asthma| exposure| sensitization| sensitivity| reduction| health.	AUG-2005	ventilation rate| homes| asthma| allergic symptoms| children|house-dust mite| atopic-dermatitis| young-children| asthma| exposure| sensitization| sensitivity| reduction| health	Bornehag, CG; Sundell, J; Hagerhed-Engman, L; Sigsgaard, T	Association between ventilation rates in 390 Swedish homes and allergic symptoms in children		INDOOR AIR	ventilation rate; homes; asthma; allergic symptoms; children	HOUSE-DUST MITE; ATOPIC-DERMATITIS; YOUNG-CHILDREN; ASTHMA; EXPOSURE; SENSITIZATION; SENSITIVITY; REDUCTION; HEALTH	The aim of the study was to test the hypothesis that a low-ventilation rate in homes is associated with an increased prevalence of asthma and allergic symptoms among children. A total of 198 cases (with at least two of three symptoms: wheezing, rhinitis, eczema) and 202 healthy controls, living in 390 homes, were examined by physicians. Ventilation rates were measured by a passive tracer gas method, and inspections were carried out in the homes. About 60% of the multi-family houses and about 80% of the single-family houses did not fulfill the minimum requirement regarding ventilation rate in the Swedish building code (0.5 air changes per hour, ach). Cases had significantly lower ventilation rates than controls and a dose-response relationship was indicated.	23	79	2005	6	10.1111/j.1600-0668.2005.00372.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus is critically dependent on the age at first infection and IL-13 production. Respiratory syncytial virus (RSV) infection in early life is suspected to play a role in the development of postbronchiolitis wheezing and asthma. Reinfection is common at all ages, but factors that determine the development of altered airway function after reinfection are not well understood. This study was conducted in a mouse model to define the role of age in determining the consequences on airway function after reinfection. Mice were infected shortly after birth or at weaning and were reinfected 5 wk later, followed by assessment of airway function, airway inflammation, and lung histopathology. Infection of mice at weaning elicited a protective airway response upon reinfection. In this age group, reinfection resulted in increased airway inflammation, but without development of airway hyperresponsiveness (AHR) or eosinophilia and decreased IL-13 levels. By contrast, neonatal infection failed to protect the airways and resulted in enhanced AHR after reinfection. This secondary response was associated with the development of airway eosinophilia, increased IL-13 levels, and mucus hyperproduction. Both CD4- and CD8-positive T cells were a source of IL-13 in the lung, and inhibition of IL-13 abolished AHR and mucus production in these mice. Inoculation of UV-inactivated virus failed to elicit these divergent responses to reinfection, emphasizing the requirement for active lung infection during initial exposure. Thus, neonatal RSV infection predisposes to the development of airway eosinophilia and enhanced AHR via an IL-13-dependent mechanism during reinfection, whereas infection at a later age protects against the development of these altered airway responses after reinfection.. childhood asthma| pulmonary-function| balb/c mice| bronchiolitis| infants| immunity| allergen| disease| risk| sensitization.	AUG 1-2005	childhood asthma| pulmonary-function| balb/c mice| bronchiolitis| infants| immunity| allergen| disease| risk| sensitization	Dakhama, A; Park, JW; Taube, C; Joetham, A; Balhorn, A; Miyahara, N; Takeda, K; Gelfand, EW	The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus is critically dependent on the age at first infection and IL-13 production		JOURNAL OF IMMUNOLOGY		CHILDHOOD ASTHMA; PULMONARY-FUNCTION; BALB/C MICE; BRONCHIOLITIS; INFANTS; IMMUNITY; ALLERGEN; DISEASE; RISK; SENSITIZATION	Respiratory syncytial virus (RSV) infection in early life is suspected to play a role in the development of postbronchiolitis wheezing and asthma. Reinfection is common at all ages, but factors that determine the development of altered airway function after reinfection are not well understood. This study was conducted in a mouse model to define the role of age in determining the consequences on airway function after reinfection. Mice were infected shortly after birth or at weaning and were reinfected 5 wk later, followed by assessment of airway function, airway inflammation, and lung histopathology. Infection of mice at weaning elicited a protective airway response upon reinfection. In this age group, reinfection resulted in increased airway inflammation, but without development of airway hyperresponsiveness (AHR) or eosinophilia and decreased IL-13 levels. By contrast, neonatal infection failed to protect the airways and resulted in enhanced AHR after reinfection. This secondary response was associated with the development of airway eosinophilia, increased IL-13 levels, and mucus hyperproduction. Both CD4- and CD8-positive T cells were a source of IL-13 in the lung, and inhibition of IL-13 abolished AHR and mucus production in these mice. Inoculation of UV-inactivated virus failed to elicit these divergent responses to reinfection, emphasizing the requirement for active lung infection during initial exposure. Thus, neonatal RSV infection predisposes to the development of airway eosinophilia and enhanced AHR via an IL-13-dependent mechanism during reinfection, whereas infection at a later age protects against the development of these altered airway responses after reinfection.	41	79	2005	8		Immunology
The Australasian Society of Clinical Immunology and Allergy position statement: summary of allergy prevention in children. A family history of allergy and asthma identifies children at high risk of allergic disease. Dietary restrictions in pregnancy are not recommended. Avoiding inhalant allergens during pregnancy has not been shown to reduce allergic disease, and is not recommended. Breastfeeding should be recommended because of other beneficial effects, but if breast feeding is not possible, a hydrolysed formula is recommended (rather than conventional cow's milk formulas) in high-risk infants only. Maternal dietary restrictions during breastfeeding are not recommended. Soy formulas and other formulas (eg, goat's milk) are not recommended for reducing food allergy risk. Complementary foods (including normal cow's milk formulas) should be delayed until a child is aged at least 4-6 months, but a preventive effect from this measure has only been demonstrated in high-risk infants. There is no evidence that an elimination diet after age 4-6 months has a protective effect, although this needs additional investigation. Further research is needed to determine the relationship between house dust mite exposure at an early age and the development of sensitisation and disease; no recommendation can yet be made about avoidance measures for preventing allergic disease. No recommendations can be made about exposure to pets in early life and the development of allergic disease. If a family already has pets it is not necessary to remove them, unless the child develops evidence of pet allergy (as assessed by an allergy specialist). Women should be advised not to smoke while pregnant, and parents should be advised not to smoke. No recommendations can be made on the use of probiotic supplements (or other microbial agents) for preventing allergic disease at this time. Immunotherapy may be considered as a treatment option for children with allergic rhinitis, and may prevent the subsequent development of asthma.. house-dust mite| childhood asthma prevention| placebo-controlled trial| fatty-acid modification| follow-up| lung-function| symptoms| risk| immunotherapy| sensitization.	MAY 2-2005	house-dust mite| childhood asthma prevention| placebo-controlled trial| fatty-acid modification| follow-up| lung-function| symptoms| risk| immunotherapy| sensitization	Prescott, SL; Tang, MLK	The Australasian Society of Clinical Immunology and Allergy position statement: summary of allergy prevention in children		MEDICAL JOURNAL OF AUSTRALIA		HOUSE-DUST MITE; CHILDHOOD ASTHMA PREVENTION; PLACEBO-CONTROLLED TRIAL; FATTY-ACID MODIFICATION; FOLLOW-UP; LUNG-FUNCTION; SYMPTOMS; RISK; IMMUNOTHERAPY; SENSITIZATION	A family history of allergy and asthma identifies children at high risk of allergic disease. Dietary restrictions in pregnancy are not recommended. Avoiding inhalant allergens during pregnancy has not been shown to reduce allergic disease, and is not recommended. Breastfeeding should be recommended because of other beneficial effects, but if breast feeding is not possible, a hydrolysed formula is recommended (rather than conventional cow's milk formulas) in high-risk infants only. Maternal dietary restrictions during breastfeeding are not recommended. Soy formulas and other formulas (eg, goat's milk) are not recommended for reducing food allergy risk. Complementary foods (including normal cow's milk formulas) should be delayed until a child is aged at least 4-6 months, but a preventive effect from this measure has only been demonstrated in high-risk infants. There is no evidence that an elimination diet after age 4-6 months has a protective effect, although this needs additional investigation. Further research is needed to determine the relationship between house dust mite exposure at an early age and the development of sensitisation and disease; no recommendation can yet be made about avoidance measures for preventing allergic disease. No recommendations can be made about exposure to pets in early life and the development of allergic disease. If a family already has pets it is not necessary to remove them, unless the child develops evidence of pet allergy (as assessed by an allergy specialist). Women should be advised not to smoke while pregnant, and parents should be advised not to smoke. No recommendations can be made on the use of probiotic supplements (or other microbial agents) for preventing allergic disease at this time. Immunotherapy may be considered as a treatment option for children with allergic rhinitis, and may prevent the subsequent development of asthma.	26	79	2005	4		General & Internal Medicine
The usefulness of skin tests to prove drug hypersensitivity. Background Suspected drug hypersensitivity is common. Only a minority of cutaneous adverse drug reactions (CADRs) are allergic in origin and will reappear after the next exposure. Methods to confirm suspected CADRs are needed and skin testing could serve as one possibility. Objectives To analyse the usefulness of skin tests in revealing drug allergy. The relevance of skin test results was evaluated with drug provocation studies. Methods During 1989-2001, 947 patients with a history of suspected CADR were examined with skin tests including patch tests (PTs) (826 patients), skin prick tests (SPTs) (935 patients) and photopatch tests (12 patients). The occurrence of positive and negative test reactions to different drugs was correlated with clinical history. Drug provocation was carried out in 246 patients. Results Antimicrobial drugs were suspected and tested most often. A positive PT reaction to one or more drug was seen in 89 of 826 (10.8%), most often to beta-lactams, clindamycin and trimethoprim. A positive SPT reaction was seen in 10 of 935 (1.1%) patients. Challenge was carried out in 17 patients with positive skin test results. Thirteen of 16 (81.2%) PT positives developed exanthema, three remained negative and one SPT-positive patient developed urticaria. Among skin test negatives, 207 of 229 (90.4%) challenges were negative and 22 of 229 (9.6%) were positive, 12 with exanthema, three with fixed drug eruptions and seven with urticaria. Conclusions Skin testing, especially the PT, was a useful screening method to find a cause of CADR if the reaction was exanthema and if antimicrobial, cardiovascular or antiepileptic drugs were suspected. The SPT detected occasional positives with antimicrobials. In cases of fixed drug eruption, PTs performed at the earlier reaction site were useful. When skin tests are negative or dubious, oral challenge should be carried out to confirm the association.. drug hypersensitivity| patch test| skin test|generalized exanthematous pustulosis| topical provocation| cutaneous reactions| adverse reactions| diagnosis| captopril| exposure| eruption| allergy| ige.	MAY-2005	drug hypersensitivity| patch test| skin test|generalized exanthematous pustulosis| topical provocation| cutaneous reactions| adverse reactions| diagnosis| captopril| exposure| eruption| allergy| ige	Lammintausta, K; Kortekangas-Savolainen, O	The usefulness of skin tests to prove drug hypersensitivity		BRITISH JOURNAL OF DERMATOLOGY	drug hypersensitivity; patch test; skin test	GENERALIZED EXANTHEMATOUS PUSTULOSIS; TOPICAL PROVOCATION; CUTANEOUS REACTIONS; ADVERSE REACTIONS; DIAGNOSIS; CAPTOPRIL; EXPOSURE; ERUPTION; ALLERGY; IGE	Background Suspected drug hypersensitivity is common. Only a minority of cutaneous adverse drug reactions (CADRs) are allergic in origin and will reappear after the next exposure. Methods to confirm suspected CADRs are needed and skin testing could serve as one possibility. Objectives To analyse the usefulness of skin tests in revealing drug allergy. The relevance of skin test results was evaluated with drug provocation studies. Methods During 1989-2001, 947 patients with a history of suspected CADR were examined with skin tests including patch tests (PTs) (826 patients), skin prick tests (SPTs) (935 patients) and photopatch tests (12 patients). The occurrence of positive and negative test reactions to different drugs was correlated with clinical history. Drug provocation was carried out in 246 patients. Results Antimicrobial drugs were suspected and tested most often. A positive PT reaction to one or more drug was seen in 89 of 826 (10.8%), most often to beta-lactams, clindamycin and trimethoprim. A positive SPT reaction was seen in 10 of 935 (1.1%) patients. Challenge was carried out in 17 patients with positive skin test results. Thirteen of 16 (81.2%) PT positives developed exanthema, three remained negative and one SPT-positive patient developed urticaria. Among skin test negatives, 207 of 229 (90.4%) challenges were negative and 22 of 229 (9.6%) were positive, 12 with exanthema, three with fixed drug eruptions and seven with urticaria. Conclusions Skin testing, especially the PT, was a useful screening method to find a cause of CADR if the reaction was exanthema and if antimicrobial, cardiovascular or antiepileptic drugs were suspected. The SPT detected occasional positives with antimicrobials. In cases of fixed drug eruption, PTs performed at the earlier reaction site were useful. When skin tests are negative or dubious, oral challenge should be carried out to confirm the association.	37	79	2005	7	10.1111/j.1365-2133.2005.06429.x	Dermatology
Bacterial and fungal components in house dust of farm children, Rudolf Steiner School children and reference children - the PARSIFAL Study. Background: Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. It has been suggested that the enhanced exposure to endotoxin is an important protective factor of farm environments. Little is known about exposure to other microbial components on farms and exposure in anthroposophic families. Objective: To assess the levels and determinants of bacterial endotoxin, mould beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in house dust of farm children, Steiner school children and reference children. Methods: Mattress and living room dust was collected in the homes of 229 farm children, 122 Steiner children and 60 and 67 of their respective reference children in five European countries. Stable dust was collected as well. All samples were analysed in one central laboratory. Determinants were assessed by questionnaire. Results: Levels of endotoxin, EPS and glucans per gram of house dust in farm homes were 1.2- to 3.2-fold higher than levels in reference homes. For Steiner children, 1.1- to 1.6-fold higher levels were observed compared with their reference children. These differences were consistently found across countries, although mean levels varied considerably. Differences between groups and between countries were also significant after adjustment for home and family characteristics. Conclusion: Farm children are not only consistently exposed to higher levels of endotoxin, but also to higher levels of mould components. Steiner school children may also be exposed to higher levels of microbial agents, but differences with reference children are much less pronounced than for farm children. Further analyses are, however, required to assess the association between exposure to these various microbial agents and allergic and airway diseases in the PARSIFAL population.. beta(1,3)-glucans| anthroposophy| children| endotoxin| farm| fungal extracellular polysaccharides| house dust| microbial exposure|anthroposophic life-style| extracellular polysaccharides| allergic diseases| culturable fungi| german homes| hay-fever| asthma| endotoxin| exposure| environments.	MAY-2005	beta(1,3)-glucans| anthroposophy| children| endotoxin| farm| fungal extracellular polysaccharides| house dust| microbial exposure|anthroposophic life-style| extracellular polysaccharides| allergic diseases| culturable fungi| german homes| hay-fever| asthma| endotoxin| exposure| environments	Schram, D; Doekes, G; Boeve, M; Douwes, J; Riedler, J; Ublagger, E; von Mutius, E; Budde, J; Pershagen, G; Nyberg, F; Alm, J; Braun-Fahrlander, C; Waser, M; Brunekreef, B	Bacterial and fungal components in house dust of farm children, Rudolf Steiner School children and reference children - the PARSIFAL Study		ALLERGY	beta(1,3)-glucans; anthroposophy; children; endotoxin; farm; fungal extracellular polysaccharides; house dust; microbial exposure	ANTHROPOSOPHIC LIFE-STYLE; EXTRACELLULAR POLYSACCHARIDES; ALLERGIC DISEASES; CULTURABLE FUNGI; GERMAN HOMES; HAY-FEVER; ASTHMA; ENDOTOXIN; EXPOSURE; ENVIRONMENTS	Background: Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. It has been suggested that the enhanced exposure to endotoxin is an important protective factor of farm environments. Little is known about exposure to other microbial components on farms and exposure in anthroposophic families. Objective: To assess the levels and determinants of bacterial endotoxin, mould beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in house dust of farm children, Steiner school children and reference children. Methods: Mattress and living room dust was collected in the homes of 229 farm children, 122 Steiner children and 60 and 67 of their respective reference children in five European countries. Stable dust was collected as well. All samples were analysed in one central laboratory. Determinants were assessed by questionnaire. Results: Levels of endotoxin, EPS and glucans per gram of house dust in farm homes were 1.2- to 3.2-fold higher than levels in reference homes. For Steiner children, 1.1- to 1.6-fold higher levels were observed compared with their reference children. These differences were consistently found across countries, although mean levels varied considerably. Differences between groups and between countries were also significant after adjustment for home and family characteristics. Conclusion: Farm children are not only consistently exposed to higher levels of endotoxin, but also to higher levels of mould components. Steiner school children may also be exposed to higher levels of microbial agents, but differences with reference children are much less pronounced than for farm children. Further analyses are, however, required to assess the association between exposure to these various microbial agents and allergic and airway diseases in the PARSIFAL population.	33	79	2005	8	10.1111/j.1398-9995.2005.00748.x	Allergy; Immunology
Proteinase-activated receptor 2 activation in the airways enhances antigen-mediated airway inflammation and airway hyperresponsiveness through different pathways. Background: Serine proteinases such as mast cell tryptase, trypsin-like enzymes, and certain allergens are important in the pathogenesis of asthma. These proteinases can activate the proteinase-activated receptor (PAR)-2, which has been shown to be upregulated in the airways of patients with asthma. Objective: The purpose of this study was to investigate PAR-2 activation in the airways during allergen challenge and its effects on the 2 principle features of asthma, airway inflammation and airway hyperresponsiveness (AHR). Methods: Proteinase-activated receptor 2 activating peptide SLIGRL-NH2 (PAR-2 activating peptide [ap]) or control peptide LSIGRL-NH2 (PAR-2 control peptide [cp]) was administered alone or in conjunction with ovalbumin intranasally to mice, and AHR and airway inflammation were evaluated. Results: PAR2ap did not induce AHR or airway inflammation in ovalbumin-sensitized mice that had not been challenged with ovalbumin. When administered with ovalbumin, PAR-2ap enhanced AHR and airway inflammation compared with ovalbumin administered alone or with PAR-2cp. The enhanced AHR persisted for 5 days, whereas the enhancement to airway inflammation dissipated. Mice administered PAR-2ap alone during the 5 days after the final antigen challenge demonstrated an additional enhancement to airway inflammation compared with the control animals. PAR-2ap administered with allergen increased TNF and IL-5 mRNA in lung tissue and IL-13 and TNF in bronchoalveolar lavage fluid. Conclusion: Exogenous PAR-2 activation in parallel with allergen challenge enhances allergen-mediated AHR and airway inflammation through distinct mechanisms. PAR-2 activation can also enhance established airway inflammation even when dissociated from exposure to allergen. Therefore, PAR-2 activation may play a pathogenic role in the development of AHR and airway inflammation.. proteinase-activated receptor 2| allergy| rodent| airway inflammation| eosinophils| il-13|microvascular endothelial-cells| epithelial-cells| mite allergens| mast-cells| asthma| hyperreactivity| tryptase| release| sensitization| induction.	MAR-2005	proteinase-activated receptor 2| allergy| rodent| airway inflammation| eosinophils| il-13|microvascular endothelial-cells| epithelial-cells| mite allergens| mast-cells| asthma| hyperreactivity| tryptase| release| sensitization| induction	Ebeling, C; Forsythe, P; Ng, J; Gordon, JR; Hollenberg, M; Vliagoftis, H	Proteinase-activated receptor 2 activation in the airways enhances antigen-mediated airway inflammation and airway hyperresponsiveness through different pathways		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	proteinase-activated receptor 2; allergy; rodent; airway inflammation; eosinophils; IL-13	MICROVASCULAR ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; MITE ALLERGENS; MAST-CELLS; ASTHMA; HYPERREACTIVITY; TRYPTASE; RELEASE; SENSITIZATION; INDUCTION	Background: Serine proteinases such as mast cell tryptase, trypsin-like enzymes, and certain allergens are important in the pathogenesis of asthma. These proteinases can activate the proteinase-activated receptor (PAR)-2, which has been shown to be upregulated in the airways of patients with asthma. Objective: The purpose of this study was to investigate PAR-2 activation in the airways during allergen challenge and its effects on the 2 principle features of asthma, airway inflammation and airway hyperresponsiveness (AHR). Methods: Proteinase-activated receptor 2 activating peptide SLIGRL-NH2 (PAR-2 activating peptide [ap]) or control peptide LSIGRL-NH2 (PAR-2 control peptide [cp]) was administered alone or in conjunction with ovalbumin intranasally to mice, and AHR and airway inflammation were evaluated. Results: PAR2ap did not induce AHR or airway inflammation in ovalbumin-sensitized mice that had not been challenged with ovalbumin. When administered with ovalbumin, PAR-2ap enhanced AHR and airway inflammation compared with ovalbumin administered alone or with PAR-2cp. The enhanced AHR persisted for 5 days, whereas the enhancement to airway inflammation dissipated. Mice administered PAR-2ap alone during the 5 days after the final antigen challenge demonstrated an additional enhancement to airway inflammation compared with the control animals. PAR-2ap administered with allergen increased TNF and IL-5 mRNA in lung tissue and IL-13 and TNF in bronchoalveolar lavage fluid. Conclusion: Exogenous PAR-2 activation in parallel with allergen challenge enhances allergen-mediated AHR and airway inflammation through distinct mechanisms. PAR-2 activation can also enhance established airway inflammation even when dissociated from exposure to allergen. Therefore, PAR-2 activation may play a pathogenic role in the development of AHR and airway inflammation.	36	79	2005	8	10.1016/j.jaci.2004.11.042	Allergy; Immunology
Health-related benefits of attaining the 8-hr ozone standard. During the 2000-2002 time period, between 36 and 56% of ozone monitors each year in the United States faded to meet the current ozone standard of 80 ppb for the fourth highest maximum 8-hr ozone concentration. We estimated the health benefits of attaining the ozone standard at these monitors using the U.S. Environmental Protection Agency's Environmental Benefits Mapping and Analysis Program. We used health impact functions based on published epidemiologic studies, and valuation functions derived from the economics literature. The estimated health benefits for 2000 and 2001 are similar in magnitude, whereas the results for 2002 are roughly twice that of each of the prior 2 years. The simple average of health impacts across the 3 years includes reductions of 800 premature deaths, 4,500 hospital and emergency department admissions, 900,000 school absences, and > 1 million minor restricted activity days. The simple average of benefits (including premature mortality) across the 3 years is $5.7 billion [90% confidence interval (0), 0.6-15-01 for the quadratic rollback simulation method and $4.9 billion (90% CI, 0.5-14.0) for the proportional rollback simulation method. Results are sensitive to the form of the standard and to assumptions about background ozone levels. If the form of the standard is based on the first highest maximum 8-hr concentration, impacts are increased by a factor of 2-3. Increasing the assumed hourly background from zero to 40 ppb reduced impacts by 30 and 60% for the proportional and quadratic attainment simulation methods, respectively.. air pollution| benefit analysis| health impact assessment| ozone| standards|minneapolis st-paul| air-pollution| hospital admissions| daily mortality| emergency-department| school absenteeism| asthma| visits| associations| philadelphia.	JAN-2005	air pollution| benefit analysis| health impact assessment| ozone| standards|minneapolis st-paul| air-pollution| hospital admissions| daily mortality| emergency-department| school absenteeism| asthma| visits| associations| philadelphia	Hubbell, BJ; Hallberg, A; McCubbin, DR; Post, E	Health-related benefits of attaining the 8-hr ozone standard		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; benefit analysis; health impact assessment; ozone; standards	MINNEAPOLIS ST-PAUL; AIR-POLLUTION; HOSPITAL ADMISSIONS; DAILY MORTALITY; EMERGENCY-DEPARTMENT; SCHOOL ABSENTEEISM; ASTHMA; VISITS; ASSOCIATIONS; PHILADELPHIA	During the 2000-2002 time period, between 36 and 56% of ozone monitors each year in the United States faded to meet the current ozone standard of 80 ppb for the fourth highest maximum 8-hr ozone concentration. We estimated the health benefits of attaining the ozone standard at these monitors using the U.S. Environmental Protection Agency's Environmental Benefits Mapping and Analysis Program. We used health impact functions based on published epidemiologic studies, and valuation functions derived from the economics literature. The estimated health benefits for 2000 and 2001 are similar in magnitude, whereas the results for 2002 are roughly twice that of each of the prior 2 years. The simple average of health impacts across the 3 years includes reductions of 800 premature deaths, 4,500 hospital and emergency department admissions, 900,000 school absences, and > 1 million minor restricted activity days. The simple average of benefits (including premature mortality) across the 3 years is $5.7 billion [90% confidence interval (0), 0.6-15-01 for the quadratic rollback simulation method and $4.9 billion (90% CI, 0.5-14.0) for the proportional rollback simulation method. Results are sensitive to the form of the standard and to assumptions about background ozone levels. If the form of the standard is based on the first highest maximum 8-hr concentration, impacts are increased by a factor of 2-3. Increasing the assumed hourly background from zero to 40 ppb reduced impacts by 30 and 60% for the proportional and quadratic attainment simulation methods, respectively.	55	79	2005	10		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Influence of a multidisciplinary paediatric allergy clinic on parental knowledge and rate of subsequent allergic reactions. Background: Studies have demonstrated that families of children with food allergy have significant deficiencies in their knowledge of how to avoid allergen exposure and how to manage allergic reactions. This study aims to assess the impact of a multidisciplinary paediatric allergy clinic consultation on parental knowledge of food allergy and to determine the rate of subsequent allergic reactions. Methods: Sixty-two subjects (< 17 years) referred with food allergy were prospectively enrolled. Parental knowledge was assessed by questionnaire and EpiPen trainer. Families saw a paediatric allergist, clinical nurse specialist and dietician. Knowledge was reassessed after 3 months and rate of allergic reactions after 1 year. Results: After one visit to the paediatric allergy clinic, there was a significant improvement in parental knowledge of allergen avoidance (26.9%, P < 0.001), managing allergic reactions (185.4%, P < 0.0001) and EpiPen usage (83.3%, P < 0.001). Additionally, there was a significant reduction in allergic reactions (P < 0.001). Children with egg, milk or multiple food allergies were more likely to suffer subsequent reactions. Conclusions: A single visit to a multidisciplinary allergy clinic considerably improves families' abilities to manage allergic reactions to foods with an accompanying reduction in allergic reactions. Young children with egg, milk or multiple food allergies were at greatest risk of further reactions.. children| education| food allergy| multidisciplinary clinic|food allergy| peanut allergy| anaphylactic reactions| ige concentrations| children| management| epinephrine| adolescents| challenges| history.	FEB-2004	children| education| food allergy| multidisciplinary clinic|food allergy| peanut allergy| anaphylactic reactions| ige concentrations| children| management| epinephrine| adolescents| challenges| history	Kapoor, S; Roberts, G; Bynoe, Y; Gaughan, M; Habibi, P; Lack, G	Influence of a multidisciplinary paediatric allergy clinic on parental knowledge and rate of subsequent allergic reactions		ALLERGY	children; education; food allergy; multidisciplinary clinic	FOOD ALLERGY; PEANUT ALLERGY; ANAPHYLACTIC REACTIONS; IGE CONCENTRATIONS; CHILDREN; MANAGEMENT; EPINEPHRINE; ADOLESCENTS; CHALLENGES; HISTORY	Background: Studies have demonstrated that families of children with food allergy have significant deficiencies in their knowledge of how to avoid allergen exposure and how to manage allergic reactions. This study aims to assess the impact of a multidisciplinary paediatric allergy clinic consultation on parental knowledge of food allergy and to determine the rate of subsequent allergic reactions. Methods: Sixty-two subjects (< 17 years) referred with food allergy were prospectively enrolled. Parental knowledge was assessed by questionnaire and EpiPen trainer. Families saw a paediatric allergist, clinical nurse specialist and dietician. Knowledge was reassessed after 3 months and rate of allergic reactions after 1 year. Results: After one visit to the paediatric allergy clinic, there was a significant improvement in parental knowledge of allergen avoidance (26.9%, P < 0.001), managing allergic reactions (185.4%, P < 0.0001) and EpiPen usage (83.3%, P < 0.001). Additionally, there was a significant reduction in allergic reactions (P < 0.001). Children with egg, milk or multiple food allergies were more likely to suffer subsequent reactions. Conclusions: A single visit to a multidisciplinary allergy clinic considerably improves families' abilities to manage allergic reactions to foods with an accompanying reduction in allergic reactions. Young children with egg, milk or multiple food allergies were at greatest risk of further reactions.	19	79	2004	7	10.1046/j.1398-9995.2003.00365.x	Allergy; Immunology
Endotoxin contamination of ovalbumin suppresses murine immunologic responses and development of airway hyper-reactivity. The reversible airway hyper-reactivity (AHR) of asthma is modeled by sensitizing and challenging mice with aerosolized ovalbumin. However, the C57BL/6 murine strain does not display the large increase in circulating IgG and IgE antibodies found in human atopy and asthma. We found that commercial ovalbumin was contaminated with lipopolysaccharide (LPS) in amounts sufficient to fully activate endothelial cells in an in vitro assay of the first step of inflammation. Desensitization of TLR4 by LPS pretreatment suppressed the inflammatory effect of ovalbumin. The presence of LPS was occult, because it does not require serum presentation and, like the LPS of Salmonella minnesota, was not suppressed by polymyxin B. Purified ovalbumin did not activate endothelial cells in vitro; however, endotoxin-free ovalbumin was far more effective than commercial material in stimulating IgE production and respiratory dysfunction in a C57BL/6 murine model of AHR. Moreover, endotoxin-free ovalbumin induced lung inflammation with alveolar enlargement and destruction in a histologic pattern that differed from the changes caused by commercial, endotoxin-contaminated ovalbumin. Reconstitution of purified ovalbumin with S. minnesota LPS decreased lung inflammation, decreased changes in lung function, and suppressed anti-ovalbumin antibody production. We conclude endotoxin contaminates ovalbumin preparations and that endotoxin co-administration with the ovalbumin antigen creates a state of tolerance in a murine model of AHR. Co-exposure to endotoxin and antigen occurs in humans through organic dusts, so murine models of AHR may reflect the clinical situation, but models based on commercial ovalbumin do not accurately reflect the effect of protein antigen alone on animal physiology.. human-endothelial-cells| toll-like receptor-2| bacterial lipopolysaccharide| escherichia-coli| allergic-asthma| kappa-b| mice| hyperresponsiveness| inflammation| exposure.	OCT 24-2003	human-endothelial-cells| toll-like receptor-2| bacterial lipopolysaccharide| escherichia-coli| allergic-asthma| kappa-b| mice| hyperresponsiveness| inflammation| exposure	Watanabe, J; Miyazaki, Y; Zimmerman, GA; Albertine, KH; McIntyre, TM	Endotoxin contamination of ovalbumin suppresses murine immunologic responses and development of airway hyper-reactivity		JOURNAL OF BIOLOGICAL CHEMISTRY		HUMAN-ENDOTHELIAL-CELLS; TOLL-LIKE RECEPTOR-2; BACTERIAL LIPOPOLYSACCHARIDE; ESCHERICHIA-COLI; ALLERGIC-ASTHMA; KAPPA-B; MICE; HYPERRESPONSIVENESS; INFLAMMATION; EXPOSURE	The reversible airway hyper-reactivity (AHR) of asthma is modeled by sensitizing and challenging mice with aerosolized ovalbumin. However, the C57BL/6 murine strain does not display the large increase in circulating IgG and IgE antibodies found in human atopy and asthma. We found that commercial ovalbumin was contaminated with lipopolysaccharide (LPS) in amounts sufficient to fully activate endothelial cells in an in vitro assay of the first step of inflammation. Desensitization of TLR4 by LPS pretreatment suppressed the inflammatory effect of ovalbumin. The presence of LPS was occult, because it does not require serum presentation and, like the LPS of Salmonella minnesota, was not suppressed by polymyxin B. Purified ovalbumin did not activate endothelial cells in vitro; however, endotoxin-free ovalbumin was far more effective than commercial material in stimulating IgE production and respiratory dysfunction in a C57BL/6 murine model of AHR. Moreover, endotoxin-free ovalbumin induced lung inflammation with alveolar enlargement and destruction in a histologic pattern that differed from the changes caused by commercial, endotoxin-contaminated ovalbumin. Reconstitution of purified ovalbumin with S. minnesota LPS decreased lung inflammation, decreased changes in lung function, and suppressed anti-ovalbumin antibody production. We conclude endotoxin contaminates ovalbumin preparations and that endotoxin co-administration with the ovalbumin antigen creates a state of tolerance in a murine model of AHR. Co-exposure to endotoxin and antigen occurs in humans through organic dusts, so murine models of AHR may reflect the clinical situation, but models based on commercial ovalbumin do not accurately reflect the effect of protein antigen alone on animal physiology.	42	79	2003	8	10.1074/jbc.M307752200	Biochemistry & Molecular Biology
The plasmin system in airway remodeling. Recent studies suggest that the plasmin system plays an active role in tissue remodeling. Plasmin degrades the extracellular matrix (ECM), either directly removing glycoproteins from ECM or by activating matrix metalloproteinases (MMPs). PAI-1 blocking MMPs may prevent ECM degradation, but inhibiting fibrinolysis leads to fibrin accumulation and fibrosis. Components of the plasmin system including tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and plasminogen activator inhibitors PAI-1 and PAI-2 are synthesised by airway cells, and inflammatory mediators affect their expression. The plasmin system, in turn, actively influences the production of inflammatory mediators,and growth factors, extending pathological structural changes in the airway. Modulation of the plasmin system might be a new pharmacological strategy that could inhibit the development of airway remodeling. (C) 2003 Elsevier Ltd. All rights reserved.. plasmin system| asthma| airway remodeling|activator inhibitor type-2| induced pulmonary-fibrosis| bronchoalveolar lavage fluid| necrosis-factor-alpha| human mast-cells| house dust mite| human-monocytes| urokinase receptor| 5-lipoxygenase pathway| neutrophil aggregation.	2003	plasmin system| asthma| airway remodeling|activator inhibitor type-2| induced pulmonary-fibrosis| bronchoalveolar lavage fluid| necrosis-factor-alpha| human mast-cells| house dust mite| human-monocytes| urokinase receptor| 5-lipoxygenase pathway| neutrophil aggregation	Kucharewicz, I; Kowal, K; Buczko, W; Bodzenta-Lukaszyk, A	The plasmin system in airway remodeling		THROMBOSIS RESEARCH	plasmin system; asthma; airway remodeling	ACTIVATOR INHIBITOR TYPE-2; INDUCED PULMONARY-FIBROSIS; BRONCHOALVEOLAR LAVAGE FLUID; NECROSIS-FACTOR-ALPHA; HUMAN MAST-CELLS; HOUSE DUST MITE; HUMAN-MONOCYTES; UROKINASE RECEPTOR; 5-LIPOXYGENASE PATHWAY; NEUTROPHIL AGGREGATION	Recent studies suggest that the plasmin system plays an active role in tissue remodeling. Plasmin degrades the extracellular matrix (ECM), either directly removing glycoproteins from ECM or by activating matrix metalloproteinases (MMPs). PAI-1 blocking MMPs may prevent ECM degradation, but inhibiting fibrinolysis leads to fibrin accumulation and fibrosis. Components of the plasmin system including tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and plasminogen activator inhibitors PAI-1 and PAI-2 are synthesised by airway cells, and inflammatory mediators affect their expression. The plasmin system, in turn, actively influences the production of inflammatory mediators,and growth factors, extending pathological structural changes in the airway. Modulation of the plasmin system might be a new pharmacological strategy that could inhibit the development of airway remodeling. (C) 2003 Elsevier Ltd. All rights reserved.	87	79	2003	7	10.1016/j.thromres.2003.10.011	Hematology; Cardiovascular System & Cardiology
Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers. Alveolar macrophages (AMs) are the predominant defense cells in the airway, and their numbers are increased in smokers and subjects with chronic obstructive pulmonary disease. This increase may result from increased recruitment, increased proliferation, or reduced cell death. Apoptosis regulates inflammatory cell survival, and p21(CIP1/WAF1) is an important inhibitory regulator of cycle progression after oxidative stress. We have investigated whether chronic smoke exposure influences the expression and localization of cell cycle and apoptotic proteins in AM and bronchial epithelial cells in vivo. The increased numbers of AMs seen in smokers were only partially due to enhanced proliferation. p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from smokers and was found predominantly within the cytoplasm. In addition, B cell lymphoma leukemia (BCl)-x(L), an antiapoptotic regulator, was also highly expressed in macrophages from smokers compared with nonsmokers and subjects with asthma. Hydrogen peroxide, an oxidative stress, induced cytoplasmic expression of p21(CiP1/WAF1) and failed to induce apoptosis in an in vitro model. These results suggested that AM and bronchial epithelial cells from smokers, in contrast to those from normal subjects and subjects with asthma, have reduced cell death. Thus, oxidative stress induced by cigarette smoking may contribute to the chronicity of inflammation in the airway, through a reduction of apoptosis.. p21(cip1/waf1)| monocytes/macrophages| apoptosis| cigarette smoke| epithelial cells|oxidative stress| chemokine receptor| cigarette smokers| g(1) arrest| kappa-b| death| dna| p21| replication| protein.	SEP 1-2002	p21(cip1/waf1)| monocytes/macrophages| apoptosis| cigarette smoke| epithelial cells|oxidative stress| chemokine receptor| cigarette smokers| g(1) arrest| kappa-b| death| dna| p21| replication| protein	Tomita, K; Caramori, G; Lim, S; Ito, K; Hanazawa, T; Oates, T; Chiselita, I; Jazrawi, E; Chung, KF; Barnes, PJ; Adcock, IM	Increased p21(CIP1/WAF1) and B cell lymphoma leukemia-x(L) expression and reduced apoptosis in alveolar macrophages from smokers		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	p21(CIP1/WAF1); monocytes/macrophages; apoptosis; cigarette smoke; epithelial cells	OXIDATIVE STRESS; CHEMOKINE RECEPTOR; CIGARETTE SMOKERS; G(1) ARREST; KAPPA-B; DEATH; DNA; P21; REPLICATION; PROTEIN	Alveolar macrophages (AMs) are the predominant defense cells in the airway, and their numbers are increased in smokers and subjects with chronic obstructive pulmonary disease. This increase may result from increased recruitment, increased proliferation, or reduced cell death. Apoptosis regulates inflammatory cell survival, and p21(CIP1/WAF1) is an important inhibitory regulator of cycle progression after oxidative stress. We have investigated whether chronic smoke exposure influences the expression and localization of cell cycle and apoptotic proteins in AM and bronchial epithelial cells in vivo. The increased numbers of AMs seen in smokers were only partially due to enhanced proliferation. p21(CIP1/WAF1) protein expression was increased in AMs and biopsies isolated from smokers and was found predominantly within the cytoplasm. In addition, B cell lymphoma leukemia (BCl)-x(L), an antiapoptotic regulator, was also highly expressed in macrophages from smokers compared with nonsmokers and subjects with asthma. Hydrogen peroxide, an oxidative stress, induced cytoplasmic expression of p21(CiP1/WAF1) and failed to induce apoptosis in an in vitro model. These results suggested that AM and bronchial epithelial cells from smokers, in contrast to those from normal subjects and subjects with asthma, have reduced cell death. Thus, oxidative stress induced by cigarette smoking may contribute to the chronicity of inflammation in the airway, through a reduction of apoptosis.	47	79	2002	8	10.1164/rccm.2104010	General & Internal Medicine; Respiratory System
Assessing the public health benefits of reduced ozone concentrations. In this paper we examine scientific evidence and related uncertainties in two steps of benefit-cost analyses of ozone reduction: estimating the health improvements attributable to reductions in ozone and determining the appropriate monetary values of these improvements. Although substantial evidence exists on molecular and physiologic impacts, the evidence needed to establish concentration-response functions is somewhat limited. Furthermore, because exposure to ozone depends on factors such as air conditioning use, past epidemiologic studies may not be directly applicable in unstudied settings. To evaluate the evidence likely to contribute significantly to benefits, we focus on four health outcomes: premature mortality, chronic asthma, respiratory hospital admissions, and minor restricted activity days. We determine concentration-response functions for these health outcomes for a hypothetical case study in Houston, Texas, using probabilistic weighting reflecting our judgment of the strength of the evidence and the possibility of confounding. We make a similar presentation for valuation, where uncertainty is due primarily to the lack of willingness-to-pay data for the population affected by ozone. We estimate that the annual monetary value of health benefits from reducing ozone concentrations in Houston is approximately $10 per person per microgram per cubic meter (24-hr average) reduced (95% confidence: interval, $0.70-$40). The central estimate exceeds past estimates by approximately a factor of five, driven by the inclusion of mortality. We discuss the implications of our findings for future analyses and determine areas of research that might help reduce the uncertainties in benefit estimation.. benefit-cost analysis| epidemiology| exposure assessment| monetary valuation| ozone| premature mortality|particulate air-pollution| daily mortality| pulmonary-function| ambient ozone| hospital admissions| united-states| lung-function| bronchiolar epithelium| cardiovascular-disease| respiratory morbidity.	DEC-2001	benefit-cost analysis| epidemiology| exposure assessment| monetary valuation| ozone| premature mortality|particulate air-pollution| daily mortality| pulmonary-function| ambient ozone| hospital admissions| united-states| lung-function| bronchiolar epithelium| cardiovascular-disease| respiratory morbidity	Levy, JI; Carrothers, TJ; Tuomisto, JT; Hammitt, JK; Evans, JS	Assessing the public health benefits of reduced ozone concentrations		ENVIRONMENTAL HEALTH PERSPECTIVES	benefit-cost analysis; epidemiology; exposure assessment; monetary valuation; ozone; premature mortality	PARTICULATE AIR-POLLUTION; DAILY MORTALITY; PULMONARY-FUNCTION; AMBIENT OZONE; HOSPITAL ADMISSIONS; UNITED-STATES; LUNG-FUNCTION; BRONCHIOLAR EPITHELIUM; CARDIOVASCULAR-DISEASE; RESPIRATORY MORBIDITY	In this paper we examine scientific evidence and related uncertainties in two steps of benefit-cost analyses of ozone reduction: estimating the health improvements attributable to reductions in ozone and determining the appropriate monetary values of these improvements. Although substantial evidence exists on molecular and physiologic impacts, the evidence needed to establish concentration-response functions is somewhat limited. Furthermore, because exposure to ozone depends on factors such as air conditioning use, past epidemiologic studies may not be directly applicable in unstudied settings. To evaluate the evidence likely to contribute significantly to benefits, we focus on four health outcomes: premature mortality, chronic asthma, respiratory hospital admissions, and minor restricted activity days. We determine concentration-response functions for these health outcomes for a hypothetical case study in Houston, Texas, using probabilistic weighting reflecting our judgment of the strength of the evidence and the possibility of confounding. We make a similar presentation for valuation, where uncertainty is due primarily to the lack of willingness-to-pay data for the population affected by ozone. We estimate that the annual monetary value of health benefits from reducing ozone concentrations in Houston is approximately $10 per person per microgram per cubic meter (24-hr average) reduced (95% confidence: interval, $0.70-$40). The central estimate exceeds past estimates by approximately a factor of five, driven by the inclusion of mortality. We discuss the implications of our findings for future analyses and determine areas of research that might help reduce the uncertainties in benefit estimation.	113	79	2001	12	10.1289/ehp.011091215	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
On the functional consequences of bronchial basement membrane thickening. Reticular basement membrane (RBM) thickness and airway responses to inhaled methacholine (MCh) were studied in perennial allergic asthma (n = 11), perennial allergic rhinitis (n = 8), seasonal allergic rhinitis (n = 5), and chronic obstructive pulmonary disease (COPD, n = 9). RBM was significantly thicker in asthma (10.1 +/- 3.7 mum) and perennial rhinitis (11.2 +/- 4.2 mum) than in seasonal rhinitis (4.7 +/- 0.7 mum) and COPD (5.2 +/- 0.7 mum). The dose (geometric mean) of MCh causing a 20% decrease of 1-s forced expiratory volume (FEV1) was significantly higher in perennial rhinitis (1,073 mug) than in asthma (106 mug). In COPD, the slope of the linear regression of all values of forced vital capacity plotted against FEV1 during the challenge was higher, and the intercept less, than in other groups, suggesting enhanced airway closure. In asthma, RBM thickness was positively correlated (r = 0.77) with the dose (geometric mean) of MCh causing a 20% decrease of FEV1 and negatively correlated (r = -0.73) with the forced vital capacity vs. FEV1 slope. We conclude that 1) RBM thickening is not unique to bronchial asthma, and 2) when present, it may protect against airway narrowing and air trapping. These findings support the opinion that RBM thickening represents an additional load on airway smooth muscle.. airway responsiveness| remodeling| asthma| chronic obstructive pulmonary disease| rhinitis|subepithelial fibrosis| airway inflammation| induced bronchoconstriction| asthma| methacholine| disease| hyperresponsiveness| responsiveness| mechanism| collagen.	SEP-2001	airway responsiveness| remodeling| asthma| chronic obstructive pulmonary disease| rhinitis|subepithelial fibrosis| airway inflammation| induced bronchoconstriction| asthma| methacholine| disease| hyperresponsiveness| responsiveness| mechanism| collagen	Milanese, M; Crimi, E; Scordamaglia, A; Riccio, A; Pellegrino, R; Canonica, GW; Brusasco, V	On the functional consequences of bronchial basement membrane thickening		JOURNAL OF APPLIED PHYSIOLOGY	airway responsiveness; remodeling; asthma; chronic obstructive pulmonary disease; rhinitis	SUBEPITHELIAL FIBROSIS; AIRWAY INFLAMMATION; INDUCED BRONCHOCONSTRICTION; ASTHMA; METHACHOLINE; DISEASE; HYPERRESPONSIVENESS; RESPONSIVENESS; MECHANISM; COLLAGEN	Reticular basement membrane (RBM) thickness and airway responses to inhaled methacholine (MCh) were studied in perennial allergic asthma (n = 11), perennial allergic rhinitis (n = 8), seasonal allergic rhinitis (n = 5), and chronic obstructive pulmonary disease (COPD, n = 9). RBM was significantly thicker in asthma (10.1 +/- 3.7 mum) and perennial rhinitis (11.2 +/- 4.2 mum) than in seasonal rhinitis (4.7 +/- 0.7 mum) and COPD (5.2 +/- 0.7 mum). The dose (geometric mean) of MCh causing a 20% decrease of 1-s forced expiratory volume (FEV1) was significantly higher in perennial rhinitis (1,073 mug) than in asthma (106 mug). In COPD, the slope of the linear regression of all values of forced vital capacity plotted against FEV1 during the challenge was higher, and the intercept less, than in other groups, suggesting enhanced airway closure. In asthma, RBM thickness was positively correlated (r = 0.77) with the dose (geometric mean) of MCh causing a 20% decrease of FEV1 and negatively correlated (r = -0.73) with the forced vital capacity vs. FEV1 slope. We conclude that 1) RBM thickening is not unique to bronchial asthma, and 2) when present, it may protect against airway narrowing and air trapping. These findings support the opinion that RBM thickening represents an additional load on airway smooth muscle.	30	79	2001	6		Physiology; Sport Sciences
Epidermal cytokines in experimental contact dermatitis. Topical exposure to a variety of xenobiotics may result in irritant as well as allergic contact dermatitis both in rodents and in humans. Despite their induction by different mechanisms, they cannot be differentiated by macroscopic appearance and, by histological examination they are both generally characterized by a perivascular mononuclear cell infiltrate and capillary hyperpermeability. Recently, cytokines, a family of inducible glycoproteins that play a pivotal role in immune and inflammatory reactions, have been identified as useful tools for differentiation of irritant and allergic contact dermatitis. In this article the role of cytokines in the development and differentiation of irritant and allergic contact dermatitis is discussed. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.. contact dermatitis| skin irritation| contact allergy| cytokines|tumor-necrosis-factor| activated langerhans cells| skin immune-system| factor-alpha| in-vivo| human keratinocytes| dendritic cells| guinea-pig| tnf-alpha| sensitization.	JAN 17-2000	contact dermatitis| skin irritation| contact allergy| cytokines|tumor-necrosis-factor| activated langerhans cells| skin immune-system| factor-alpha| in-vivo| human keratinocytes| dendritic cells| guinea-pig| tnf-alpha| sensitization	Corsini, E; Galli, CL	Epidermal cytokines in experimental contact dermatitis		TOXICOLOGY	contact dermatitis; skin irritation; contact allergy; cytokines	TUMOR-NECROSIS-FACTOR; ACTIVATED LANGERHANS CELLS; SKIN IMMUNE-SYSTEM; FACTOR-ALPHA; IN-VIVO; HUMAN KERATINOCYTES; DENDRITIC CELLS; GUINEA-PIG; TNF-ALPHA; SENSITIZATION	Topical exposure to a variety of xenobiotics may result in irritant as well as allergic contact dermatitis both in rodents and in humans. Despite their induction by different mechanisms, they cannot be differentiated by macroscopic appearance and, by histological examination they are both generally characterized by a perivascular mononuclear cell infiltrate and capillary hyperpermeability. Recently, cytokines, a family of inducible glycoproteins that play a pivotal role in immune and inflammatory reactions, have been identified as useful tools for differentiation of irritant and allergic contact dermatitis. In this article the role of cytokines in the development and differentiation of irritant and allergic contact dermatitis is discussed. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.	47	79	2000	9	10.1016/S0300-483X(99)00145-6	Pharmacology & Pharmacy; Toxicology
ALLERGY Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Growing up on a dairy farm protects children from allergy, hay fever, and asthma. A mechanism linking exposure to this endotoxin (bacterial lipopolysaccharide)-rich environment with protection has remained elusive. Here we show that chronic exposure to low-dose endotoxin or farm dust protects mice from developing house dust mite (HDM)-induced asthma. Endotoxin reduced epithelial cell cytokines that activate dendritic cells (DCs), thus suppressing type 2 immunity to HDMs. Loss of the ubiquitin-modifying enzyme A20 in lung epithelium abolished the protective effect. A single-nucleotide polymorphism in the gene encoding A20 was associated with allergy and asthma risk in children growing up on farms. Thus, the farming environment protects from allergy by modifying the communication between barrier epithelial cells and DCs through A20 induction.. nf-kappa-b| childhood asthma| airway inflammation| mite allergen| enzyme a20| exposure| responses| children| immunity| environment.	SEP 4-2015	nf-kappa-b| childhood asthma| airway inflammation| mite allergen| enzyme a20| exposure| responses| children| immunity| environment	Schuijs, MJ; Willart, MA; Vergote, K; Gras, D; Deswarte, K; Ege, MJ; Madeira, FB; Beyaert, R; van Loo, G; Bracher, F; von Mutius, E; Chanez, P; Lambrecht, BN; Hammad, H	ALLERGY Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells		SCIENCE		NF-KAPPA-B; CHILDHOOD ASTHMA; AIRWAY INFLAMMATION; MITE ALLERGEN; ENZYME A20; EXPOSURE; RESPONSES; CHILDREN; IMMUNITY; ENVIRONMENT	Growing up on a dairy farm protects children from allergy, hay fever, and asthma. A mechanism linking exposure to this endotoxin (bacterial lipopolysaccharide)-rich environment with protection has remained elusive. Here we show that chronic exposure to low-dose endotoxin or farm dust protects mice from developing house dust mite (HDM)-induced asthma. Endotoxin reduced epithelial cell cytokines that activate dendritic cells (DCs), thus suppressing type 2 immunity to HDMs. Loss of the ubiquitin-modifying enzyme A20 in lung epithelium abolished the protective effect. A single-nucleotide polymorphism in the gene encoding A20 was associated with allergy and asthma risk in children growing up on farms. Thus, the farming environment protects from allergy by modifying the communication between barrier epithelial cells and DCs through A20 induction.	33	78	2015	5	10.1126/science.aac6623	Science & Technology - Other Topics
The Patient-Centered Medical Home: A Review of Recent Research. The patient-centered medical home is an important innovation in health care delivery. There is a need to assess the scope and substance of published research on medical homes. This article reviews published evaluations of medical home care for the period 2007 to 2010. Chief findings from these evaluations as a whole include associations between the provision of medical home care and improved quality, in addition to decreased utilization associated with medical home care in high-cost areas such as emergency department use. However, fewer associations were found across evaluations between medical home care and enhanced patient or family experiences. The early medical home research appears to reflect both the wide variation in how medical homes are being designed and implemented in practice and in how researchers are choosing to evaluate patient-centered medical home design and implementation. While some aspects of medical home care show promise, continued evolution of medical home evaluative research is needed.. health care quality| literature review| patient-centered medical home| primary care| research design|primary-care| health-care| children| access| asthma| delivery| services| system| needs| model.	DEC-2012	health care quality| literature review| patient-centered medical home| primary care| research design|primary-care| health-care| children| access| asthma| delivery| services| system| needs| model	Hoff, T; Weller, W; DePuccio, M	The Patient-Centered Medical Home: A Review of Recent Research		MEDICAL CARE RESEARCH AND REVIEW	health care quality; literature review; patient-centered medical home; primary care; research design	PRIMARY-CARE; HEALTH-CARE; CHILDREN; ACCESS; ASTHMA; DELIVERY; SERVICES; SYSTEM; NEEDS; MODEL	The patient-centered medical home is an important innovation in health care delivery. There is a need to assess the scope and substance of published research on medical homes. This article reviews published evaluations of medical home care for the period 2007 to 2010. Chief findings from these evaluations as a whole include associations between the provision of medical home care and improved quality, in addition to decreased utilization associated with medical home care in high-cost areas such as emergency department use. However, fewer associations were found across evaluations between medical home care and enhanced patient or family experiences. The early medical home research appears to reflect both the wide variation in how medical homes are being designed and implemented in practice and in how researchers are choosing to evaluate patient-centered medical home design and implementation. While some aspects of medical home care show promise, continued evolution of medical home evaluative research is needed.	39	78	2012	26	10.1177/1077558712447688	Health Care Sciences & Services
Instrumental Variable Estimation of Causal Risk Ratios and Causal Odds Ratios in Mendelian Randomization Analyses. In this paper, the authors describe different instrumental variable (IV) estimators of causal risk ratios and odds ratios with particular attention to methods that can handle continuously measured exposures. The authors present this discussion in the context of a Mendelian randomization analysis of the effect of body mass index (BMI; weight (kg)/height (m)(2)) on the risk of asthma at age 7 years (Avon Longitudinal Study of Parents and Children, 19911992). The authors show that the multiplicative structural mean model (MSMM) and the multiplicative generalized method of moments (MGMM) estimator produce identical estimates of the causal risk ratio. In the example, MSMM and MGMM estimates suggested an inverse relation between BMI and asthma but other IV estimates suggested a positive relation, although all estimates had wide confidence intervals. An interaction between the associations of BMI and fat mass and obesity-associated (FTO) genotype with asthma explained the different directions of the different estimates, and a simulation study supported the observation that MSMM/MGMM estimators are negatively correlated with the other estimators when such an interaction is present. The authors conclude that point estimates from various IV methods can differ in practical applications. Based on the theoretical properties of the estimators, structural mean models make weaker assumptions than other IV estimators and can therefore be expected to be consistent in a wider range of situations.. causal inference| causality| confounding factors (epidemiology)| effect modifiers (epidemiology)| generalized method of moments| instrumental variables| mendelian randomization analysis| structural models|structural mean models| generalized-method| inference| trials| identification| noncompliance| epidemiology| equation| bias| endogeneity.	JUN 15-2011	causal inference| causality| confounding factors (epidemiology)| effect modifiers (epidemiology)| generalized method of moments| instrumental variables| mendelian randomization analysis| structural models|structural mean models| generalized-method| inference| trials| identification| noncompliance| epidemiology| equation| bias| endogeneity	Palmer, TM; Sterne, JAC; Harbord, RM; Lawlor, DA; Sheehan, NA; Meng, S; Granell, R; Smith, GD; Didelez, V	Instrumental Variable Estimation of Causal Risk Ratios and Causal Odds Ratios in Mendelian Randomization Analyses		AMERICAN JOURNAL OF EPIDEMIOLOGY	causal inference; causality; confounding factors (epidemiology); effect modifiers (epidemiology); generalized method of moments; instrumental variables; Mendelian randomization analysis; structural models	STRUCTURAL MEAN MODELS; GENERALIZED-METHOD; INFERENCE; TRIALS; IDENTIFICATION; NONCOMPLIANCE; EPIDEMIOLOGY; EQUATION; BIAS; ENDOGENEITY	In this paper, the authors describe different instrumental variable (IV) estimators of causal risk ratios and odds ratios with particular attention to methods that can handle continuously measured exposures. The authors present this discussion in the context of a Mendelian randomization analysis of the effect of body mass index (BMI; weight (kg)/height (m)(2)) on the risk of asthma at age 7 years (Avon Longitudinal Study of Parents and Children, 19911992). The authors show that the multiplicative structural mean model (MSMM) and the multiplicative generalized method of moments (MGMM) estimator produce identical estimates of the causal risk ratio. In the example, MSMM and MGMM estimates suggested an inverse relation between BMI and asthma but other IV estimates suggested a positive relation, although all estimates had wide confidence intervals. An interaction between the associations of BMI and fat mass and obesity-associated (FTO) genotype with asthma explained the different directions of the different estimates, and a simulation study supported the observation that MSMM/MGMM estimators are negatively correlated with the other estimators when such an interaction is present. The authors conclude that point estimates from various IV methods can differ in practical applications. Based on the theoretical properties of the estimators, structural mean models make weaker assumptions than other IV estimators and can therefore be expected to be consistent in a wider range of situations.	62	78	2011	12	10.1093/aje/kwr026	Public, Environmental & Occupational Health
Gene-environment interactions in human disease: nuisance or opportunity?. Many environmental risk factors for common, complex human diseases have been revealed by epidemiologic studies, but how genotypes at specific loci modulate individual responses to environmental risk factors is largely unknown. Gene-environment interactions will be missed in genome-wide association studies and could account for some of the 'missing heritability' for these diseases. In this review, we focus on asthma as a model disease for studying gene-environment interactions because of relatively large numbers of candidate gene-environment interactions with asthma risk in the literature. Identifying these interactions using genome-wide approaches poses formidable methodological problems, and elucidating molecular mechanisms for these interactions has been challenging. We suggest that studying gene-environment interactions in animal models, although more tractable, might not be sufficient to shed light on the genetic architecture of human diseases. Lastly, we propose avenues for future studies to find gene environment interactions.. early respiratory-infections| genome-wide association| quantitative trait loci| tobacco-smoke exposure| childhood asthma| air-pollution| lung-function| hay-fever| occupational asthma| hygiene hypothesis.	MAR-2011	early respiratory-infections| genome-wide association| quantitative trait loci| tobacco-smoke exposure| childhood asthma| air-pollution| lung-function| hay-fever| occupational asthma| hygiene hypothesis	Ober, C; Vercelli, D	Gene-environment interactions in human disease: nuisance or opportunity?		TRENDS IN GENETICS		EARLY RESPIRATORY-INFECTIONS; GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; TOBACCO-SMOKE EXPOSURE; CHILDHOOD ASTHMA; AIR-POLLUTION; LUNG-FUNCTION; HAY-FEVER; OCCUPATIONAL ASTHMA; HYGIENE HYPOTHESIS	Many environmental risk factors for common, complex human diseases have been revealed by epidemiologic studies, but how genotypes at specific loci modulate individual responses to environmental risk factors is largely unknown. Gene-environment interactions will be missed in genome-wide association studies and could account for some of the 'missing heritability' for these diseases. In this review, we focus on asthma as a model disease for studying gene-environment interactions because of relatively large numbers of candidate gene-environment interactions with asthma risk in the literature. Identifying these interactions using genome-wide approaches poses formidable methodological problems, and elucidating molecular mechanisms for these interactions has been challenging. We suggest that studying gene-environment interactions in animal models, although more tractable, might not be sufficient to shed light on the genetic architecture of human diseases. Lastly, we propose avenues for future studies to find gene environment interactions.	115	78	2011	9	10.1016/j.tig.2010.12.004	Genetics & Heredity
Environmental tobacco smoke (ETS) and respiratory health in children. Environmental tobacco smoke (ETS) is a major risk factor for poor lung health in children. Although parental smoking is the commonest source of ETS exposure to children, they are also exposed to ETS in schools, restaurants, public places and public transport vehicles. Apart from containing thousands of chemicals, the particle size in the ETS is much smaller than the main stream smoke, and therefore has a greater penetrability in the airways of children. Exposure to ETS has been shown to be associated with increased prevalence of upper respiratory tract infections, wheeze, asthma and lower respiratory tract infections. Even developing fetuses are exposed to ETS via the umbilical cord blood if the mother is exposed to tobacco smoke. The placenta also does not offer any barrier to the penetration of ETS into the fetus. The immune system in these babies is more deviated toward the allergic and asthmatic inflammatory phenotype and therefore makes them more prone to develop asthma later in life. An increased awareness of the harmful effects of ETS on children's health is warranted.. environmental tobacco smoke (ets)| asthma| respiratory tract infection| children|infant-death-syndrome| active maternal smoking| childhood lung-function| age 5 years| parental smoking| passive smoking| risk-factors| 1st year| postnatal exposure| family-history.	AUG-2009	environmental tobacco smoke (ets)| asthma| respiratory tract infection| children|infant-death-syndrome| active maternal smoking| childhood lung-function| age 5 years| parental smoking| passive smoking| risk-factors| 1st year| postnatal exposure| family-history	Cheraghi, M; Salvi, S	Environmental tobacco smoke (ETS) and respiratory health in children		EUROPEAN JOURNAL OF PEDIATRICS	Environmental tobacco smoke (ETS); Asthma; Respiratory tract infection; Children	INFANT-DEATH-SYNDROME; ACTIVE MATERNAL SMOKING; CHILDHOOD LUNG-FUNCTION; AGE 5 YEARS; PARENTAL SMOKING; PASSIVE SMOKING; RISK-FACTORS; 1ST YEAR; POSTNATAL EXPOSURE; FAMILY-HISTORY	Environmental tobacco smoke (ETS) is a major risk factor for poor lung health in children. Although parental smoking is the commonest source of ETS exposure to children, they are also exposed to ETS in schools, restaurants, public places and public transport vehicles. Apart from containing thousands of chemicals, the particle size in the ETS is much smaller than the main stream smoke, and therefore has a greater penetrability in the airways of children. Exposure to ETS has been shown to be associated with increased prevalence of upper respiratory tract infections, wheeze, asthma and lower respiratory tract infections. Even developing fetuses are exposed to ETS via the umbilical cord blood if the mother is exposed to tobacco smoke. The placenta also does not offer any barrier to the penetration of ETS into the fetus. The immune system in these babies is more deviated toward the allergic and asthmatic inflammatory phenotype and therefore makes them more prone to develop asthma later in life. An increased awareness of the harmful effects of ETS on children's health is warranted.	118	78	2009	9	10.1007/s00431-009-0967-3	Pediatrics
Alveolar Macrophages Transport Pathogens to Lung Draining Lymph Nodes. The first step in inducing pulmonary adaptive immunity to allergens and airborne pathogens is Ag acquisition and transport to the lung draining lymph nodes (dLN). Dendritic cells (DC) sample the airways, and active transfer of Ag to the lung dLN is considered an exclusive property of migratory DC. However, alveolar macrophages (AM) are the first phagocytes to contact inhaled particulate matter. Although having well-defined immunoregulatory capabilities, AM are generally considered as restricted to the alveoli. We show that murine AM constitutively migrate from lung to dLN and that following exposure to Streptococcus pneumoniae, AM rapidly transport bacteria to this site. Thus AM, and not DC, appear responsible for the earliest delivery of these bacteria to secondary lymphoid tissue. The identification of this novel transport pathway has important consequences for our understanding of lung immunity and suggests more widespread roles for macrophages in the transport of Ags to lymphoid organs than previously appreciated. The Journal of Immunology, 2009, 183: 1983-1989.. pulmonary dendritic cells| pneumococcal pneumonia| in-vivo| b-cells| subcapsular sinus| siglec-f| mouse| antigen| inflammation| infection.	AUG 1-2009	pulmonary dendritic cells| pneumococcal pneumonia| in-vivo| b-cells| subcapsular sinus| siglec-f| mouse| antigen| inflammation| infection	Kirby, AC; Coles, MC; Kaye, PM	Alveolar Macrophages Transport Pathogens to Lung Draining Lymph Nodes		JOURNAL OF IMMUNOLOGY		PULMONARY DENDRITIC CELLS; PNEUMOCOCCAL PNEUMONIA; IN-VIVO; B-CELLS; SUBCAPSULAR SINUS; SIGLEC-F; MOUSE; ANTIGEN; INFLAMMATION; INFECTION	The first step in inducing pulmonary adaptive immunity to allergens and airborne pathogens is Ag acquisition and transport to the lung draining lymph nodes (dLN). Dendritic cells (DC) sample the airways, and active transfer of Ag to the lung dLN is considered an exclusive property of migratory DC. However, alveolar macrophages (AM) are the first phagocytes to contact inhaled particulate matter. Although having well-defined immunoregulatory capabilities, AM are generally considered as restricted to the alveoli. We show that murine AM constitutively migrate from lung to dLN and that following exposure to Streptococcus pneumoniae, AM rapidly transport bacteria to this site. Thus AM, and not DC, appear responsible for the earliest delivery of these bacteria to secondary lymphoid tissue. The identification of this novel transport pathway has important consequences for our understanding of lung immunity and suggests more widespread roles for macrophages in the transport of Ags to lymphoid organs than previously appreciated. The Journal of Immunology, 2009, 183: 1983-1989.	34	78	2009	7	10.4049/jimmunol.0901089	Immunology
Symptoms and Medication Use in Children with Asthma and Traffic-Related Sources of Fine Particle Pollution. BACKGROUND: Exposure to ambient fine particles [particulate matter <= 2.5 mu m diameter (PM(2.5))] is a potential factor in the exacerbation of asthma. National air quality particle standards consider total mass, not composition or sources, and may not protect against health impacts related to specific components. OBJECTIVE: We examined associations between daily exposure to fine particle components and sources, and symptoms and medication use in children with asthma. METHODS: Children with asthma (n = 149) 4-12 years of age were enrolled in a year-long study. We analyzed particle samples for trace elements (X-ray fluorescence) and elemental carbon (light reflectance). Using factor analysis/source apportionment, we identified particle sources (e.g., motor vehicle emissions) and quantified daily contributions. Symptoms and medication use were recorded on study diaries. Repeated measures logistic regression models examined associations between health outcomes and particle exposures as elemental concentrations and source contributions. RESULTS: More than half of mean PM(2.5) was attributed to traffic-related sources motor vehicles (42%) and road dust (12%). Increased likelihood of symptoms and inhaler use was largest for 3-day averaged exposures to traffic-related sources or their elemental constituents and ranged from a 10% increased likelihood of wheeze for each 5-mu g/m(3) increase in particles from motor vehicles to a 28% increased likelihood of shortness of breath for increases in road dust. Neither the other sources identified nor PM(2.5) alone was associated with increased health outcome risks. CONCLUSIONS: Linking respiratory health effects to specific particle pollution composition or sources is critical to efforts to protect public health. We associated increased risk of symptoms and inhaler use in children with asthma with exposure to traffic-related fine particles.. childhood asthma| fine particle pollution| pm(2.5)| respiratory morbidity| source apportionment| traffic pollution|airborne particulate matter| air-pollution| respiratory symptoms| source-apportionment| lung-function| emission factors| 1st year| association| pm2.5| mortality.	JUL-2009	childhood asthma| fine particle pollution| pm(2.5)| respiratory morbidity| source apportionment| traffic pollution|airborne particulate matter| air-pollution| respiratory symptoms| source-apportionment| lung-function| emission factors| 1st year| association| pm2.5| mortality	Gent, JF; Koutrakis, P; Belanger, K; Triche, E; Holford, TR; Bracken, MB; Leaderer, BP	Symptoms and Medication Use in Children with Asthma and Traffic-Related Sources of Fine Particle Pollution		ENVIRONMENTAL HEALTH PERSPECTIVES	childhood asthma; fine particle pollution; PM(2.5); respiratory morbidity; source apportionment; traffic pollution	AIRBORNE PARTICULATE MATTER; AIR-POLLUTION; RESPIRATORY SYMPTOMS; SOURCE-APPORTIONMENT; LUNG-FUNCTION; EMISSION FACTORS; 1ST YEAR; ASSOCIATION; PM2.5; MORTALITY	BACKGROUND: Exposure to ambient fine particles [particulate matter <= 2.5 mu m diameter (PM(2.5))] is a potential factor in the exacerbation of asthma. National air quality particle standards consider total mass, not composition or sources, and may not protect against health impacts related to specific components. OBJECTIVE: We examined associations between daily exposure to fine particle components and sources, and symptoms and medication use in children with asthma. METHODS: Children with asthma (n = 149) 4-12 years of age were enrolled in a year-long study. We analyzed particle samples for trace elements (X-ray fluorescence) and elemental carbon (light reflectance). Using factor analysis/source apportionment, we identified particle sources (e.g., motor vehicle emissions) and quantified daily contributions. Symptoms and medication use were recorded on study diaries. Repeated measures logistic regression models examined associations between health outcomes and particle exposures as elemental concentrations and source contributions. RESULTS: More than half of mean PM(2.5) was attributed to traffic-related sources motor vehicles (42%) and road dust (12%). Increased likelihood of symptoms and inhaler use was largest for 3-day averaged exposures to traffic-related sources or their elemental constituents and ranged from a 10% increased likelihood of wheeze for each 5-mu g/m(3) increase in particles from motor vehicles to a 28% increased likelihood of shortness of breath for increases in road dust. Neither the other sources identified nor PM(2.5) alone was associated with increased health outcome risks. CONCLUSIONS: Linking respiratory health effects to specific particle pollution composition or sources is critical to efforts to protect public health. We associated increased risk of symptoms and inhaler use in children with asthma with exposure to traffic-related fine particles.	49	78	2009	7	10.1289/ehp.0800335	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
"Use of CpG oligonucleotides in treatment of asthma and allergic disease. In the last several decades, there has been a marked increase in the prevalence of atopic disorders including asthma in ""Western"" societies; a relationship has been identified between lack of early-life exposure to microbes or microbial products and increased susceptibility to atopic disorders. The innate immune system is activated by early microbial exposures, many of which utilize one of the Toll-like receptors, and there has been significant interest in studying how ligation of TLRs may be therapeutically useful. CpG oligonucleotides (CpG-ODN, resembling bacterial DNA) engage TLR-9 on B-cells, dendritic cells and other cell types, resulting in a cascade that includes induction of Th1-type and T-regulatory-type immune responses. Preclinical models of asthma have demonstrated that CpG-ODN are potent inhibitors of atopic responses, suppressing Th2 cytokine and, reducing airway eosinophilia, systemic levels of IgE, and bronchial hyperreactivity-in short the critical attributes of the asthmatic phenotype. In models of chronic allergen exposure, CpG-ODN are also effective at preventing the development of airway remodeling. In established asthma, CpG-ODN can reverse manifestations of disease both when used alone or in combination with allergen immunotherapy. Early clinical trials have had mixed results, including a significant benefit when CpG-ODN were conjugated to ragweed allergen in an allergic rhinitis immunotherapy study, but only limited efficacy seen when administered prior to allergen challenge in asthmatics. Further study of CpG-ODNs for the treatment of asthma and other atopic disorders is warranted by existing data. Published by Elsevier B.V.. asthma| atopy| inflammation| cpg oligonucleotides| immunotherapy|dendritic cells| murine model| immunostimulatory dna| indoleamine 2,3-dioxygenase| airway inflammation| cutting edge| oligodeoxynucleotides| motifs| expression| antigen."	MAR 28-2009	asthma| atopy| inflammation| cpg oligonucleotides| immunotherapy|dendritic cells| murine model| immunostimulatory dna| indoleamine 2,3-dioxygenase| airway inflammation| cutting edge| oligodeoxynucleotides| motifs| expression| antigen	Fonseca, DE; Kline, JN	Use of CpG oligonucleotides in treatment of asthma and allergic disease		ADVANCED DRUG DELIVERY REVIEWS	Asthma; Atopy; Inflammation; CpG oligonucleotides; Immunotherapy	DENDRITIC CELLS; MURINE MODEL; IMMUNOSTIMULATORY DNA; INDOLEAMINE 2,3-DIOXYGENASE; AIRWAY INFLAMMATION; CUTTING EDGE; OLIGODEOXYNUCLEOTIDES; MOTIFS; EXPRESSION; ANTIGEN	"In the last several decades, there has been a marked increase in the prevalence of atopic disorders including asthma in ""Western"" societies; a relationship has been identified between lack of early-life exposure to microbes or microbial products and increased susceptibility to atopic disorders. The innate immune system is activated by early microbial exposures, many of which utilize one of the Toll-like receptors, and there has been significant interest in studying how ligation of TLRs may be therapeutically useful. CpG oligonucleotides (CpG-ODN, resembling bacterial DNA) engage TLR-9 on B-cells, dendritic cells and other cell types, resulting in a cascade that includes induction of Th1-type and T-regulatory-type immune responses. Preclinical models of asthma have demonstrated that CpG-ODN are potent inhibitors of atopic responses, suppressing Th2 cytokine and, reducing airway eosinophilia, systemic levels of IgE, and bronchial hyperreactivity-in short the critical attributes of the asthmatic phenotype. In models of chronic allergen exposure, CpG-ODN are also effective at preventing the development of airway remodeling. In established asthma, CpG-ODN can reverse manifestations of disease both when used alone or in combination with allergen immunotherapy. Early clinical trials have had mixed results, including a significant benefit when CpG-ODN were conjugated to ragweed allergen in an allergic rhinitis immunotherapy study, but only limited efficacy seen when administered prior to allergen challenge in asthmatics. Further study of CpG-ODNs for the treatment of asthma and other atopic disorders is warranted by existing data. Published by Elsevier B.V."	42	78	2009	7	10.1016/j.addr.2008.12.007	Pharmacology & Pharmacy
Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force. The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing, readers can refer to the Allergy Diagnostic Practice Parameters. A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen specific IgE (called sensitization). It does not necessarily mean clinical allergy (ie, allergic symptoms with exposure). It is important for this reason that the allergy evaluation be based on the patient's history and directed by a health care professional with sufficient understanding of allergy diagnostic testing to use the information obtained from his/her evaluation of the patient to determine (1) what allergy diagnostic tests to order, (2) how to interpret the allergy diagnostic test results, and (3) how to use the information obtained from the allergy evaluation to develop an appropriate therapeutic treatment plan.. nutrition examination survey| intradermal skin-tests| insect sting allergy| venom immunotherapy| practice parameter| adverse-reactions| national-health| peanut allergy| lung-function| food allergy.	DEC-2008	nutrition examination survey| intradermal skin-tests| insect sting allergy| venom immunotherapy| practice parameter| adverse-reactions| national-health| peanut allergy| lung-function| food allergy	Cox, L; Williams, B; Sicherer, S; Oppenheimer, J; Sher, L; Hamilton, R; Golden, D	Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		NUTRITION EXAMINATION SURVEY; INTRADERMAL SKIN-TESTS; INSECT STING ALLERGY; VENOM IMMUNOTHERAPY; PRACTICE PARAMETER; ADVERSE-REACTIONS; NATIONAL-HEALTH; PEANUT ALLERGY; LUNG-FUNCTION; FOOD ALLERGY	The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing, readers can refer to the Allergy Diagnostic Practice Parameters. A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen specific IgE (called sensitization). It does not necessarily mean clinical allergy (ie, allergic symptoms with exposure). It is important for this reason that the allergy evaluation be based on the patient's history and directed by a health care professional with sufficient understanding of allergy diagnostic testing to use the information obtained from his/her evaluation of the patient to determine (1) what allergy diagnostic tests to order, (2) how to interpret the allergy diagnostic test results, and (3) how to use the information obtained from the allergy evaluation to develop an appropriate therapeutic treatment plan.	49	78	2008	13		Allergy; Immunology
Recent advances in the understanding of egg allergens: Basic, industrial, and clinical perspectives. The emergence of egg allergy. has had both industrial and clinical implications. In industrialized countries, egg allergy accounts for one of the most prevalent food hypersensitivities, especially in children. Atopic dermatitis represents the most common clinical manifestation in infancy; however, the range of clinical signs is broad and encompasses life-threatening anaphylaxis. The dominant egg allergens are proteins and are mainly present in the egg white, for example, ovalbumin, ovomucoid, ovotransferrin, and lysozyme. However, egg yolk also displays low-level allergenicity, for example, (x-livetin. Strict avoidance of the offending food remains the most common recommendation for egg-allergic individuals. Nevertheless, the omnipresence of egg-derived components in prepackaged or prepared foods makes it difficult. Therefore, more efficient preventive approaches are investigated to protect consumers from inadvertent exposure and ensuing adverse reactions. On the one hand, commercial kits have become readily available that allow for the detection of egg contaminants at trace levels. On the other hand, attempts to produce hypoallergenic egg-containing products through food-processing techniques have met with promising results, but the approach is limited due to its potentially undesirable effects on the unique functional and sensory attributes of egg proteins. Therefore, the development of preventive or curative strategies for egg allergy remains strongly warranted. Pilot studies have suggested that oral immunotherapy (IT) with raw or cooked preparations of egg may represent a safe alternative, immediately available to allergic subjects, but remains applicable to only nonanaphylactic patients. Due to the limitations of conventional IT, novel forms of immunotherapy are sought based on information obtained from the-molecular characterization of major egg allergens. In the past decade, promising approaches to the treatment and prevention of egg allergy have been explored and include, among others, the production of hypoallergenic recombinant egg proteins, the development of customized peptides, and bacterial-mediated immunotherapy. Nonspecific approaches have also been evaluated, and preliminary trials with the use of probiotic bacteria have yielded encouraging results. The current understanding of egg allergens offers novel approaches toward the making of food products safe for human consumption and the development of efficient immunotherapeutic strategies.. egg allergy| ovalbumin| ovomucoid| lysozyme| food processing| allergen detection| immunotherapy| immune tolerance|ovomucoid 3rd domain| immunoglobulin-e production| oral tolerance induction| amino-acid-sequence| t-cell epitope| immunostimulatory dna-sequence| antilysozyme antibody hyhel-63| linked-immunosorbent-assay| chicken serum-albumin| th2 immune-responses.	JUL 9-2008	egg allergy| ovalbumin| ovomucoid| lysozyme| food processing| allergen detection| immunotherapy| immune tolerance|ovomucoid 3rd domain| immunoglobulin-e production| oral tolerance induction| amino-acid-sequence| t-cell epitope| immunostimulatory dna-sequence| antilysozyme antibody hyhel-63| linked-immunosorbent-assay| chicken serum-albumin| th2 immune-responses	Mine, Y; Yang, M	Recent advances in the understanding of egg allergens: Basic, industrial, and clinical perspectives		JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY	egg allergy; ovalbumin; ovomucoid; lysozyme; food processing; allergen detection; immunotherapy; immune tolerance	OVOMUCOID 3RD DOMAIN; IMMUNOGLOBULIN-E PRODUCTION; ORAL TOLERANCE INDUCTION; AMINO-ACID-SEQUENCE; T-CELL EPITOPE; IMMUNOSTIMULATORY DNA-SEQUENCE; ANTILYSOZYME ANTIBODY HYHEL-63; LINKED-IMMUNOSORBENT-ASSAY; CHICKEN SERUM-ALBUMIN; TH2 IMMUNE-RESPONSES	The emergence of egg allergy. has had both industrial and clinical implications. In industrialized countries, egg allergy accounts for one of the most prevalent food hypersensitivities, especially in children. Atopic dermatitis represents the most common clinical manifestation in infancy; however, the range of clinical signs is broad and encompasses life-threatening anaphylaxis. The dominant egg allergens are proteins and are mainly present in the egg white, for example, ovalbumin, ovomucoid, ovotransferrin, and lysozyme. However, egg yolk also displays low-level allergenicity, for example, (x-livetin. Strict avoidance of the offending food remains the most common recommendation for egg-allergic individuals. Nevertheless, the omnipresence of egg-derived components in prepackaged or prepared foods makes it difficult. Therefore, more efficient preventive approaches are investigated to protect consumers from inadvertent exposure and ensuing adverse reactions. On the one hand, commercial kits have become readily available that allow for the detection of egg contaminants at trace levels. On the other hand, attempts to produce hypoallergenic egg-containing products through food-processing techniques have met with promising results, but the approach is limited due to its potentially undesirable effects on the unique functional and sensory attributes of egg proteins. Therefore, the development of preventive or curative strategies for egg allergy remains strongly warranted. Pilot studies have suggested that oral immunotherapy (IT) with raw or cooked preparations of egg may represent a safe alternative, immediately available to allergic subjects, but remains applicable to only nonanaphylactic patients. Due to the limitations of conventional IT, novel forms of immunotherapy are sought based on information obtained from the-molecular characterization of major egg allergens. In the past decade, promising approaches to the treatment and prevention of egg allergy have been explored and include, among others, the production of hypoallergenic recombinant egg proteins, the development of customized peptides, and bacterial-mediated immunotherapy. Nonspecific approaches have also been evaluated, and preliminary trials with the use of probiotic bacteria have yielded encouraging results. The current understanding of egg allergens offers novel approaches toward the making of food products safe for human consumption and the development of efficient immunotherapeutic strategies.	303	78	2008	27	10.1021/jf8001153	Agriculture; Chemistry; Food Science & Technology
Inflammation-induced uptake and degradation of the lymphatic endothelial hyaluronan receptor LYVE-1. The hyaluronan receptor LYVE-1 is selectively expressed in the endothelium of lymphatic capillaries, where it has been proposed to function in hyaluronan clearance and hyaluronan-mediated leukocyte adhesion. However, recent studies suggest that hyaluronan homeostasis is unperturbed in LYVE-1(-/-) mice and that lymphatic adhesion/transmigration may be largely mediated by ICAM-1 and VCAM-1 rather than LYVE-1. Here we have explored the possibility that LYVE-1 functions during inflammation and report that the receptor is down-regulated by pro-inflammatory cytokines. Using cultured primary lymphatic endothelial cells, we show that surface expression of LYVE-1 is rapidly and reversibly lost after exposure to tumor necrosis factor-alpha( TNF alpha) and TNF beta via internalization and degradation of the receptor in lysosomes, coupled with a shutdown in gene expression. Curiously, internalization does not result in significant uptake of hyaluronan, a process that is largely insensitive to the novel LYVE-1 adhesion blocking monoclonal antibody 3A, and proceeds almost equally in resting and inflammation-activated lymphatic endothelial cells. Finally, we show that TNF can induce down-modulation of LYVE-1 in ex vivo murine dermal tissue explants and present evidence that the process occurs in vivo, in the context of murine allergen-induced skin inflammation. These findings suggest that LYVE-1 can function independently of hyaluronan and have implications for the use of LYVE-1 as a histological marker for lymphangiogenesis in human pathology.. necrosis-factor-alpha| l-selectin ligand| major e-selectin| endocytosis hare| dendritic cells| binding proteins| gene-expression| tnf-alpha| cd44| lymphangiogenesis.	NOV 16-2007	necrosis-factor-alpha| l-selectin ligand| major e-selectin| endocytosis hare| dendritic cells| binding proteins| gene-expression| tnf-alpha| cd44| lymphangiogenesis	Johnson, LA; Prevo, R; Clasper, S; Jackson, DG	Inflammation-induced uptake and degradation of the lymphatic endothelial hyaluronan receptor LYVE-1		JOURNAL OF BIOLOGICAL CHEMISTRY		NECROSIS-FACTOR-ALPHA; L-SELECTIN LIGAND; MAJOR E-SELECTIN; ENDOCYTOSIS HARE; DENDRITIC CELLS; BINDING PROTEINS; GENE-EXPRESSION; TNF-ALPHA; CD44; LYMPHANGIOGENESIS	The hyaluronan receptor LYVE-1 is selectively expressed in the endothelium of lymphatic capillaries, where it has been proposed to function in hyaluronan clearance and hyaluronan-mediated leukocyte adhesion. However, recent studies suggest that hyaluronan homeostasis is unperturbed in LYVE-1(-/-) mice and that lymphatic adhesion/transmigration may be largely mediated by ICAM-1 and VCAM-1 rather than LYVE-1. Here we have explored the possibility that LYVE-1 functions during inflammation and report that the receptor is down-regulated by pro-inflammatory cytokines. Using cultured primary lymphatic endothelial cells, we show that surface expression of LYVE-1 is rapidly and reversibly lost after exposure to tumor necrosis factor-alpha( TNF alpha) and TNF beta via internalization and degradation of the receptor in lysosomes, coupled with a shutdown in gene expression. Curiously, internalization does not result in significant uptake of hyaluronan, a process that is largely insensitive to the novel LYVE-1 adhesion blocking monoclonal antibody 3A, and proceeds almost equally in resting and inflammation-activated lymphatic endothelial cells. Finally, we show that TNF can induce down-modulation of LYVE-1 in ex vivo murine dermal tissue explants and present evidence that the process occurs in vivo, in the context of murine allergen-induced skin inflammation. These findings suggest that LYVE-1 can function independently of hyaluronan and have implications for the use of LYVE-1 as a histological marker for lymphangiogenesis in human pathology.	59	78	2007	10	10.1074/jbc.M702889200	Biochemistry & Molecular Biology
Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong. Aims To assess the relationship between levels of ambient air pollutants and hospitalization rates for asthma in Hong Kong (HK). Methods This is a retrospective ecological study. Data of daily emergency hospital admissions to 15 major hospitals in HK for asthma and indices of air pollutants [sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone (O-3), particulates with an aerodynamic diameter of < 10 mu m particulate matter (PM10) and 2.5 mu m (PM2.5)] and meteorological variables from January 2000 to December 2005 were obtained from several government departments. Analysis was performed by the generalized additive models with Poisson distribution. The effects of time trend, season, other cyclical factors, temperature and humidity were adjusted. Autocorrelation and overdispersion were corrected. Results Altogether, 69 716 admissions were assessed. Significant associations were found between hospital admissions for asthma and levels of NO2, O-3, PM10 and PM2.5. The relative risks (RR) for hospitalization for every 10 mu g/m(3) increase in NO2, O-3, PM10 and PM2.5 were 1.028, 1.034, 1.019 and 1.021, respectively, at a lag day that ranged from cumulative lag 0-4 to 0-5. In a multi-pollutant model, O-3 was significantly associated with increased admissions for asthma. The younger age group (0-14 years) tended to have a higher RR for each 10 mu g/m(3) increase in pollutants than those aged 15-65 years. The elderly (aged >= 65 years) had a shorter 'best' lag time to develop asthma exacerbation following exposure to pollutants than those aged < 65 years. Conclusion Adverse effects of ambient concentrations of air pollutants on hospitalization rates for asthma are evident. Measures to improve air quality in HK are urgently needed.. age| air pollution| asthma| exacerbation| hong kong|emergency-department visits| acute respiratory syndrome| ambient air| cardiovascular-diseases| heart-failure| admissions| children| mortality| cities| associations.	SEP-2007	age| air pollution| asthma| exacerbation| hong kong|emergency-department visits| acute respiratory syndrome| ambient air| cardiovascular-diseases| heart-failure| admissions| children| mortality| cities| associations	Ko, FWS; Tam, W; Wong, TW; Lai, CKW; Wong, GWK; Leung, TF; Ng, SSS; Hui, DSC	Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong		CLINICAL AND EXPERIMENTAL ALLERGY	age; air pollution; asthma; exacerbation; Hong Kong	EMERGENCY-DEPARTMENT VISITS; ACUTE RESPIRATORY SYNDROME; AMBIENT AIR; CARDIOVASCULAR-DISEASES; HEART-FAILURE; ADMISSIONS; CHILDREN; MORTALITY; CITIES; ASSOCIATIONS	Aims To assess the relationship between levels of ambient air pollutants and hospitalization rates for asthma in Hong Kong (HK). Methods This is a retrospective ecological study. Data of daily emergency hospital admissions to 15 major hospitals in HK for asthma and indices of air pollutants [sulphur dioxide (SO2), nitrogen dioxide (NO2), ozone (O-3), particulates with an aerodynamic diameter of < 10 mu m particulate matter (PM10) and 2.5 mu m (PM2.5)] and meteorological variables from January 2000 to December 2005 were obtained from several government departments. Analysis was performed by the generalized additive models with Poisson distribution. The effects of time trend, season, other cyclical factors, temperature and humidity were adjusted. Autocorrelation and overdispersion were corrected. Results Altogether, 69 716 admissions were assessed. Significant associations were found between hospital admissions for asthma and levels of NO2, O-3, PM10 and PM2.5. The relative risks (RR) for hospitalization for every 10 mu g/m(3) increase in NO2, O-3, PM10 and PM2.5 were 1.028, 1.034, 1.019 and 1.021, respectively, at a lag day that ranged from cumulative lag 0-4 to 0-5. In a multi-pollutant model, O-3 was significantly associated with increased admissions for asthma. The younger age group (0-14 years) tended to have a higher RR for each 10 mu g/m(3) increase in pollutants than those aged 15-65 years. The elderly (aged >= 65 years) had a shorter 'best' lag time to develop asthma exacerbation following exposure to pollutants than those aged < 65 years. Conclusion Adverse effects of ambient concentrations of air pollutants on hospitalization rates for asthma are evident. Measures to improve air quality in HK are urgently needed.	40	78	2007	8	10.1111/j.1365-2222.2007.02791.x	Allergy; Immunology
Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care. Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referral centers. Objective: To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting. Methods: Youngsters aged 6-18 years with hay fever were enrolled from general practices and randomly assigned to receive placebo or grass pollen mix for 2 years. The primary outcome was the mean daily total symptom score (scale 0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and itching eyes during the months May-August of the second treatment year. Results: Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91 verum, 77 placebo). The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo (difference for verum minus placebo: -0.08, 95% CI, -0.66-0.50; P =.78). No differences were found for rescue medication-free days, disease-specific quality of life, and overall evaluation of the treatment effect. Local side effects were more frequent in the verum group (39% vs 17% of participants; P =.001). Conclusion: Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents. Clinical implications: Currently, SLIT cannot be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy.. immunotherapy| sublingual| grass pollen| allergic rhinitis| child| adolescent| primary care|seasonal allergic rhinoconjunctivitis| placebo-controlled evaluation| randomized controlled-trial| house-dust mite| quality-of-life| double-blind| swallow immunotherapy| pediatric-patients| children| rhinitis.	APR-2007	immunotherapy| sublingual| grass pollen| allergic rhinitis| child| adolescent| primary care|seasonal allergic rhinoconjunctivitis| placebo-controlled evaluation| randomized controlled-trial| house-dust mite| quality-of-life| double-blind| swallow immunotherapy| pediatric-patients| children| rhinitis	Roder, E; Berger, MY; Hop, WCJ; Bernsen, RMD; de Groot, H; van Wijk, RG	Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	immunotherapy; sublingual; grass pollen; allergic rhinitis; child; adolescent; primary care	SEASONAL ALLERGIC RHINOCONJUNCTIVITIS; PLACEBO-CONTROLLED EVALUATION; RANDOMIZED CONTROLLED-TRIAL; HOUSE-DUST MITE; QUALITY-OF-LIFE; DOUBLE-BLIND; SWALLOW IMMUNOTHERAPY; PEDIATRIC-PATIENTS; CHILDREN; RHINITIS	Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referral centers. Objective: To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting. Methods: Youngsters aged 6-18 years with hay fever were enrolled from general practices and randomly assigned to receive placebo or grass pollen mix for 2 years. The primary outcome was the mean daily total symptom score (scale 0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and itching eyes during the months May-August of the second treatment year. Results: Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91 verum, 77 placebo). The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo (difference for verum minus placebo: -0.08, 95% CI, -0.66-0.50; P =.78). No differences were found for rescue medication-free days, disease-specific quality of life, and overall evaluation of the treatment effect. Local side effects were more frequent in the verum group (39% vs 17% of participants; P =.001). Conclusion: Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents. Clinical implications: Currently, SLIT cannot be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy.	31	78	2007	7	10.1016/j.jaci.2006.12.651	Allergy; Immunology
Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea. The anti-inflammatory and anti-allergic effects of the essential oil of Cordia verbenacea (Boraginaceae) and some of its active compounds were evaluated. Systemic treatment with the essential oil of Cordia verbenacea (300-600 mg/kg, p.o.) reduced carrageenan-induced rat paw oedema, myeloperoxidase activity and the mouse oedema elicited by carrageenan, bradykinin, substance P, histamine and platelet-activating factor. It also prevented carrageenan-evoked exudation and the neutrophil influx to the rat pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches. Moreover, Cordia verbenacea oil inhibited the oedema caused by Apis mellifera venom or ovalbumin in sensitized rats and ovalbumin-evoked allergic pleurisy. The essential oil significantly decreased TNF alpha, without affecting IL-1 beta production, in carrageenan-injected rat paws. Neither the PGE(2) formation after intrapleural injection of carrageenan nor the COX-1 or COX-2 activities in vitro were affected by the essential oil. Of high interest, the paw edema induced by carrageenan in mice was markedly inhibited by both sesquiterpenic compounds obtained from the essential oil: alpha-humulene and trans-caryophyllene (50 mg/kg, p.o.). Collectively, the present results showed marked anti-inflammatory effects for the essential oil of Cordia verbenacea and some active compounds, probably by interfering with TNFa production. Cordia verbenacea essential oil or its constituents might represent new therapeutic options for the treatment of inflammatory diseases. (c) 2006 Elsevier Ireland Ltd. All rights reserved.. essential oil| cordia verbenacea| inflammation| allergy| tnf alpha| active compounds|carrageenan-induced inflammation| crude leaf extract| pharmacological assay| up-regulation| plant-origin| nitric-oxide| rat| edema| modulation| cyclooxygenase-2.	MAR 21-2007	essential oil| cordia verbenacea| inflammation| allergy| tnf alpha| active compounds|carrageenan-induced inflammation| crude leaf extract| pharmacological assay| up-regulation| plant-origin| nitric-oxide| rat| edema| modulation| cyclooxygenase-2	Passos, GF; Fernandes, ES; da Cunha, FM; Ferreira, J; Pianowski, LF; Campos, MM; Calixto, JB	Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea		JOURNAL OF ETHNOPHARMACOLOGY	essential oil; Cordia verbenacea; inflammation; allergy; TNF alpha; active compounds	CARRAGEENAN-INDUCED INFLAMMATION; CRUDE LEAF EXTRACT; PHARMACOLOGICAL ASSAY; UP-REGULATION; PLANT-ORIGIN; NITRIC-OXIDE; RAT; EDEMA; MODULATION; CYCLOOXYGENASE-2	The anti-inflammatory and anti-allergic effects of the essential oil of Cordia verbenacea (Boraginaceae) and some of its active compounds were evaluated. Systemic treatment with the essential oil of Cordia verbenacea (300-600 mg/kg, p.o.) reduced carrageenan-induced rat paw oedema, myeloperoxidase activity and the mouse oedema elicited by carrageenan, bradykinin, substance P, histamine and platelet-activating factor. It also prevented carrageenan-evoked exudation and the neutrophil influx to the rat pleura and the neutrophil migration into carrageenan-stimulated mouse air pouches. Moreover, Cordia verbenacea oil inhibited the oedema caused by Apis mellifera venom or ovalbumin in sensitized rats and ovalbumin-evoked allergic pleurisy. The essential oil significantly decreased TNF alpha, without affecting IL-1 beta production, in carrageenan-injected rat paws. Neither the PGE(2) formation after intrapleural injection of carrageenan nor the COX-1 or COX-2 activities in vitro were affected by the essential oil. Of high interest, the paw edema induced by carrageenan in mice was markedly inhibited by both sesquiterpenic compounds obtained from the essential oil: alpha-humulene and trans-caryophyllene (50 mg/kg, p.o.). Collectively, the present results showed marked anti-inflammatory effects for the essential oil of Cordia verbenacea and some active compounds, probably by interfering with TNFa production. Cordia verbenacea essential oil or its constituents might represent new therapeutic options for the treatment of inflammatory diseases. (c) 2006 Elsevier Ireland Ltd. All rights reserved.	36	78	2007	11	10.1016/j.jep.2006.09.032	Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine
Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures. Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.. asthma| corticosteroids| house dust mite| allergy| sublingual immunotherapy|randomized controlled-trial| double-blind| dermatophagoides-pteronyssinus| swallow immunotherapy| inhaled corticosteroids| clinical-efficacy| follow-up| rhinitis| extract| safety.	FEB-2007	asthma| corticosteroids| house dust mite| allergy| sublingual immunotherapy|randomized controlled-trial| double-blind| dermatophagoides-pteronyssinus| swallow immunotherapy| inhaled corticosteroids| clinical-efficacy| follow-up| rhinitis| extract| safety	Pham-Thi, N; Scheinmann, P; Fadel, R; Combebias, A; Andre, C	Assessment of sublingual immunotherapy efficacy in children with house dust mite-induced allergic asthma optimally controlled by pharmacologic treatment and mite-avoidance measures		PEDIATRIC ALLERGY AND IMMUNOLOGY	asthma; corticosteroids; house dust mite; allergy; sublingual immunotherapy	RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; DERMATOPHAGOIDES-PTERONYSSINUS; SWALLOW IMMUNOTHERAPY; INHALED CORTICOSTEROIDS; CLINICAL-EFFICACY; FOLLOW-UP; RHINITIS; EXTRACT; SAFETY	Although several studies have demonstrated the efficacy of subcutaneous immunotherapy in allergic asthma, few have shown the same benefit using sublingual immunotherapy (SLIT) in asthmatic patients. This study was conducted to assess the efficacy of house dust mite (HDM) SLIT in addition to allergen avoidance and standard pharmacologic treatment. A double-blind, placebo-controlled trial was performed in 111 children (aged 5-15 yr) with HDM-induced mild-to-moderate asthma. After a 4-week baseline phase, patients were randomly assigned to receive SLIT with tablets of HDM extract (n = 55) or placebo (n = 56) for 18 months. Pharmacologic treatment was adjusted every 3 months following a step-down approach. Asthma symptom scores, reduction in use of inhaled corticosteroids and inhaled beta(2)-agonists, rhinitis symptoms, lung function tests, skin sensitivity to HDM, dust mite-specific immunoglobulin (Ig) E and IgG(4), and quality of life (QoL) were assessed during the study. After 18 months of treatment, diurnal and nocturnal asthma symptoms scores did not show significant differences between SLIT and placebo groups. Inhaled corticosteroids and inhaled beta(2)-agonists use was reduced in both groups without significant differences between groups. There were no significant differences in lung function (forced expiratory volume in 1 s and peak flow rate variations) between groups. Rhinitis symptom score decreased in both groups, with no difference between the two groups. The severity dimension of QoL was significantly improved in the SLIT group (age 6-12 yr). SLIT induced a significant reduction of skin sensitivity to HDM (p < 0.01) and a significant increase in HDM-specific IgE and IgG(4) antibodies (p < 0.001) in the SLIT group compared with the placebo group. SLIT was well tolerated with mild/moderate local adverse events. No severe systemic reactions were reported. This study indicates that, when mild-moderate asthmatic children are optimally controlled by pharmacologic treatment and HDM avoidance, SLIT does not provide additional benefit, despite a significant reduction in allergic response to HDM. Under such conditions, only a complete, but ethically unfeasible, discontinuation of inhaled corticosteroid would have demonstrated a possible benefit of SLIT.	44	78	2007	11	10.1111/j.1399-3038.2006.00475.x	Allergy; Immunology; Pediatrics
Healthy immune response to allergens: T regulatory cells and more. The specific immune response to allergens is decisive in the development of clinically healthy or allergic states. In healthy individuals, the B-cell response varies between there being no response and the production of IgG(4)- or IgG(1)-dominating allergen-specific antibodies in the presence or absence of low amounts of IgE. If a detectable immune response is mounted, T regulatory type 1 (Tr1) cells specific for common environmental allergens consistently represent the dominant subset in healthy individuals. Exposure to high doses of allergens leads to a high concentration of specific IgG(4), detectable IgE and a TO type of immune response. Induction of IL-10- and TGF-beta-producing TO cells, IgG(4) isotype blocking antibodies, and suppressed mast cells, basophils and eosinophils represent major components of a relatively normalized immune response after allergen-specific immunotherapy (SIT).. in-vivo| bee venom| autoimmune-diseases| antibody-responses| atopic-dermatitis| dendritic cells| immunotherapy| il-10| expression| tolerance.	DEC-2006	in-vivo| bee venom| autoimmune-diseases| antibody-responses| atopic-dermatitis| dendritic cells| immunotherapy| il-10| expression| tolerance	Akdis, M	Healthy immune response to allergens: T regulatory cells and more		CURRENT OPINION IN IMMUNOLOGY		IN-VIVO; BEE VENOM; AUTOIMMUNE-DISEASES; ANTIBODY-RESPONSES; ATOPIC-DERMATITIS; DENDRITIC CELLS; IMMUNOTHERAPY; IL-10; EXPRESSION; TOLERANCE	The specific immune response to allergens is decisive in the development of clinically healthy or allergic states. In healthy individuals, the B-cell response varies between there being no response and the production of IgG(4)- or IgG(1)-dominating allergen-specific antibodies in the presence or absence of low amounts of IgE. If a detectable immune response is mounted, T regulatory type 1 (Tr1) cells specific for common environmental allergens consistently represent the dominant subset in healthy individuals. Exposure to high doses of allergens leads to a high concentration of specific IgG(4), detectable IgE and a TO type of immune response. Induction of IL-10- and TGF-beta-producing TO cells, IgG(4) isotype blocking antibodies, and suppressed mast cells, basophils and eosinophils represent major components of a relatively normalized immune response after allergen-specific immunotherapy (SIT).	58	78	2006	7	10.1016/j.coi.2006.06.003	Immunology
Health effects of the 2003 Southern California wildfires on children. Rationale: In late October 2003, Southern California wildfires burned more than 3,000 km(2). The wildfires produced heavy smoke that affected several communities participating in the University of Southern California Children's Health Study (CHS). Objectives: To study the acute effects of fire smoke on the health of CHS participants. Methods: A questionnaire was used to assess smoke exposure and occurrence of symptoms among CHS high-school students (n = 873; age, 17-18 yr) and elementary-school children (n = 5,551; age, 6-7 yr), in a total of 16 communities. Estimates of particulate matter (PM10) concentrations during the 5 d with the highest fire activity were used to characterize community smoke level. Main Results: All symptoms (nose, eyes, and throat irritations; cough; bronchitis; cold; wheezing; asthma attacks), medication usage, and physician visits were associated with individually reported exposure differences within communities. Risks increased monotonically with the number of reported smoky days. For most outcomes, reporting rates between communities were also associated with the fire-related PM10 levels. Associations tended to be strongest among those without asthma. Individuals with asthma were more likely to take preventive action, such as wearing masks or staying indoors during the fire. Conclusions: Exposure to wildfire smoke was associated with increased eye and respiratory symptoms, medication use, and physician visits.. air pollution| asthma| sore throat| wheezing|ambient air-pollution| respiratory health| particulate matter| forest-fires| exposure| quality| visits| asthma| smoke.	DEC 1-2006	air pollution| asthma| sore throat| wheezing|ambient air-pollution| respiratory health| particulate matter| forest-fires| exposure| quality| visits| asthma| smoke	Kunzli, N; Avol, E; Wu, J; Gauderman, WJ; Rappaport, E; Millstein, J; Bennion, J; McConnell, R; Gilliland, FD; Berhane, K; Lurmann, F; Winer, A; Peters, JM	Health effects of the 2003 Southern California wildfires on children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	air pollution; asthma; sore throat; wheezing	AMBIENT AIR-POLLUTION; RESPIRATORY HEALTH; PARTICULATE MATTER; FOREST-FIRES; EXPOSURE; QUALITY; VISITS; ASTHMA; SMOKE	Rationale: In late October 2003, Southern California wildfires burned more than 3,000 km(2). The wildfires produced heavy smoke that affected several communities participating in the University of Southern California Children's Health Study (CHS). Objectives: To study the acute effects of fire smoke on the health of CHS participants. Methods: A questionnaire was used to assess smoke exposure and occurrence of symptoms among CHS high-school students (n = 873; age, 17-18 yr) and elementary-school children (n = 5,551; age, 6-7 yr), in a total of 16 communities. Estimates of particulate matter (PM10) concentrations during the 5 d with the highest fire activity were used to characterize community smoke level. Main Results: All symptoms (nose, eyes, and throat irritations; cough; bronchitis; cold; wheezing; asthma attacks), medication usage, and physician visits were associated with individually reported exposure differences within communities. Risks increased monotonically with the number of reported smoky days. For most outcomes, reporting rates between communities were also associated with the fire-related PM10 levels. Associations tended to be strongest among those without asthma. Individuals with asthma were more likely to take preventive action, such as wearing masks or staying indoors during the fire. Conclusions: Exposure to wildfire smoke was associated with increased eye and respiratory symptoms, medication use, and physician visits.	25	78	2006	8	10.1164/rccm.200604-519OC	General & Internal Medicine; Respiratory System
The PASTURE project: EU support for the improvement of knowledge about risk factors and preventive factors for atopy in Europe. Since January 2002, the European Commission is funding a large project, 'Protection against Allergy - Study in Rural Environments' (PASTURE; contract no. QLK4-2001-00250), under the Fifth Framework Program in the field of epidemiology of allergic diseases. The aim of this paper was to describe the background and design as well as the aims of the project. Asthma and allergic disorders are a major public health problem in many Western countries. The aetiology of asthma and allergic disease remains poorly understood despite considerable research. Epidemiology has the potential to add greatly to the understanding by elucidating the risk factors for asthma and allergic disease and thereby suggesting productive avenues for research into causation and prevention. Several risk factors for the development of asthma and atopic disease in children such as passive smoke exposure during pregnancy and infancy, low birth weight or high body mass index later in life have been described. Furthermore, there is consistent evidence that the prevalence of atopy increases with higher socio-economic status. Levels of air pollution such as ozone, NO2, SO2 and particles are likely to provoke acute exacerbations of pre-existent respiratory disease. Their role in the inception of asthma and allergies remains to be clarified. Allergen exposure has been linked to the development of atopic sensitization to that particular allergen in children as well as in adults with occupational exposures. Exposure to house dust mite or cat allergen is, however, unlikely to contribute to the development of childhood asthma. In turn, pet keeping in the first year of life, particularly, dog keeping, has been inversely related to the development of wheeze and atopic illnesses. Several prospective birth cohort studies found a decreased prevalence of atopic disease in children having daily contact to pets, in particular to cats and dogs, during early infancy (1, 2). The protective effect might be attributable to allergen or other exposures associated with pet ownership, but may also in part be because of the removal of pets in families with sensitized or symptomatic children or in families with a positive history for atopy at the time the child was born.. allergy| asthma| atopic sensitization| farming| hygiene hypothesis| infectious disease| microbial stimuli| toll-like receptors|house-dust endotoxin| respiratory-syncytial-virus| toll-like receptor-2| allergic sensitization| farmers children| early-life| hay-fever| 1st year| school-age| asthma.	APR-2006	allergy| asthma| atopic sensitization| farming| hygiene hypothesis| infectious disease| microbial stimuli| toll-like receptors|house-dust endotoxin| respiratory-syncytial-virus| toll-like receptor-2| allergic sensitization| farmers children| early-life| hay-fever| 1st year| school-age| asthma	von Mutius, E; Schmid, S	The PASTURE project: EU support for the improvement of knowledge about risk factors and preventive factors for atopy in Europe		ALLERGY	allergy; asthma; atopic sensitization; farming; hygiene hypothesis; infectious disease; microbial stimuli; toll-like receptors	HOUSE-DUST ENDOTOXIN; RESPIRATORY-SYNCYTIAL-VIRUS; TOLL-LIKE RECEPTOR-2; ALLERGIC SENSITIZATION; FARMERS CHILDREN; EARLY-LIFE; HAY-FEVER; 1ST YEAR; SCHOOL-AGE; ASTHMA	Since January 2002, the European Commission is funding a large project, 'Protection against Allergy - Study in Rural Environments' (PASTURE; contract no. QLK4-2001-00250), under the Fifth Framework Program in the field of epidemiology of allergic diseases. The aim of this paper was to describe the background and design as well as the aims of the project. Asthma and allergic disorders are a major public health problem in many Western countries. The aetiology of asthma and allergic disease remains poorly understood despite considerable research. Epidemiology has the potential to add greatly to the understanding by elucidating the risk factors for asthma and allergic disease and thereby suggesting productive avenues for research into causation and prevention. Several risk factors for the development of asthma and atopic disease in children such as passive smoke exposure during pregnancy and infancy, low birth weight or high body mass index later in life have been described. Furthermore, there is consistent evidence that the prevalence of atopy increases with higher socio-economic status. Levels of air pollution such as ozone, NO2, SO2 and particles are likely to provoke acute exacerbations of pre-existent respiratory disease. Their role in the inception of asthma and allergies remains to be clarified. Allergen exposure has been linked to the development of atopic sensitization to that particular allergen in children as well as in adults with occupational exposures. Exposure to house dust mite or cat allergen is, however, unlikely to contribute to the development of childhood asthma. In turn, pet keeping in the first year of life, particularly, dog keeping, has been inversely related to the development of wheeze and atopic illnesses. Several prospective birth cohort studies found a decreased prevalence of atopic disease in children having daily contact to pets, in particular to cats and dogs, during early infancy (1, 2). The protective effect might be attributable to allergen or other exposures associated with pet ownership, but may also in part be because of the removal of pets in families with sensitized or symptomatic children or in families with a positive history for atopy at the time the child was born.	38	78	2006	7	10.1111/j.1398-9995.2006.01009.x	Allergy; Immunology
Prenatal dichlorodiphenyldichloroethylene (DDE) and asthma in children. Prevalence of asthma increases with increasing dichlorodiphenyldichloroethylene (DDE) levels. However, the effect of early-life exposure, the fundamental window of exposure, is unknown. We assessed the association between prenatal DDE and other organochlorine compounds, and atopy and asthma during infancy. All women presenting for antenatal care in Menorca (Spain) over 12 months starting in mid-1997 were invited to take part in a longitudinal study; 482 children were subsequently enrolled, and 468 (97.1%) provided complete outcome data up to the fourth year of study. Prenatal exposure of organochlorine compounds was measured in cord serum in 405 (83%) children. Asthma was defined on the basis of wheezing at 4 years of age, persistent wheezing, or doctor-diagnosed asthma. We measured specific immunoglobulin-E (IgE) against house dust mite, cat, and grass in sera extracted at 4 years of age. DDE (median=1.03 ng/mL) was detected in all children, as well as hexachlorobenzene (0.68 ng/mL) and polychlorobiphenyls (0.69 ng/mL). Wheezing at 4 years of age increased with DDE concentration, particularly at the highest quartile [9% in the lowest quartile (<0.57 ng/mL) vs. 19% in the highest quartile (1.90 ng/mL); relative risk=2.63 (95% confidence interval 1.19-4.69), adjusting for maternal asthma, breast-feeding, education, social class, or other organochlorines]. The association was not modified by IgE sensitization and occurred with the same strength among nonatopic subjects and among those with persistent wheezing or diagnosed asthma. DDE was not associated with atopy alone. Prenatal exposure to DDE residues may contribute to development of asthma.. asthma| atopy| children| dde dichlorodiphenyldichloroethylene| organochlorines|organochlorine compounds| immune-system| cord blood| exposure| health| hexachlorobenzene| associations| suppression| infections| childhood.	DEC-2005	asthma| atopy| children| dde dichlorodiphenyldichloroethylene| organochlorines|organochlorine compounds| immune-system| cord blood| exposure| health| hexachlorobenzene| associations| suppression| infections| childhood	Sunyer, J; Torrent, M; Munoz-Ortiz, L; Ribas-Fito, N; Carrizo, D; Grimalt, J; Anto, JM; Cullinan, P	Prenatal dichlorodiphenyldichloroethylene (DDE) and asthma in children		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; atopy; children; DDE dichlorodiphenyldichloroethylene; organochlorines	ORGANOCHLORINE COMPOUNDS; IMMUNE-SYSTEM; CORD BLOOD; EXPOSURE; HEALTH; HEXACHLOROBENZENE; ASSOCIATIONS; SUPPRESSION; INFECTIONS; CHILDHOOD	Prevalence of asthma increases with increasing dichlorodiphenyldichloroethylene (DDE) levels. However, the effect of early-life exposure, the fundamental window of exposure, is unknown. We assessed the association between prenatal DDE and other organochlorine compounds, and atopy and asthma during infancy. All women presenting for antenatal care in Menorca (Spain) over 12 months starting in mid-1997 were invited to take part in a longitudinal study; 482 children were subsequently enrolled, and 468 (97.1%) provided complete outcome data up to the fourth year of study. Prenatal exposure of organochlorine compounds was measured in cord serum in 405 (83%) children. Asthma was defined on the basis of wheezing at 4 years of age, persistent wheezing, or doctor-diagnosed asthma. We measured specific immunoglobulin-E (IgE) against house dust mite, cat, and grass in sera extracted at 4 years of age. DDE (median=1.03 ng/mL) was detected in all children, as well as hexachlorobenzene (0.68 ng/mL) and polychlorobiphenyls (0.69 ng/mL). Wheezing at 4 years of age increased with DDE concentration, particularly at the highest quartile [9% in the lowest quartile (<0.57 ng/mL) vs. 19% in the highest quartile (1.90 ng/mL); relative risk=2.63 (95% confidence interval 1.19-4.69), adjusting for maternal asthma, breast-feeding, education, social class, or other organochlorines]. The association was not modified by IgE sensitization and occurred with the same strength among nonatopic subjects and among those with persistent wheezing or diagnosed asthma. DDE was not associated with atopy alone. Prenatal exposure to DDE residues may contribute to development of asthma.	36	78	2005	4	10.1289/ehp.8127	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
High-resolution computed tomography imaging of airway disease in infants with cystic fibrosis. Rationale: The development of early lung disease in patients with cystic fibrosis (CF) remains poorly defined. Objective: Determine whether asymptomatic infants with CF have evidence for changes in airway structure when assessed by high-resolution computed tomography, and whether airway structure correlates with airway function in this age group. Methods: Thirteen infants with CF (8-33 mo) and 13 control infants (7-25 mo) were evaluated. Airway wall and lumen areas were measured from three 1-mm-thick cross-sectional images obtained from upper, middle, and lower lobes during a respiratory pause with the lungs inflated to an airway pressure of 20 cm H2O. Lung tissue density was measured from images obtained during a respiratory pause at FRC. Forced expiratory flows were measured by the rapid thoracic compression technique in 11 infants with CF. Results: Airway wall area increased more per unit increase in airway size, whereas airway lumen area increased less per unit increase in airway size in the CF than in the control group. Among infants with CF, a greater ratio of wall to lumen area correlated with lower airway function. In addition, lung density at relaxed (passive) FRC was lower for infants with Cl: than for control infants (0.38 vs. 0.43 g/ml; p < 0.02). Conclusions: Our results indicate that infants with CF have thickened airway walls, narrowed airway lumens, and air trapping, when assessed by high-resolution computed tomography, and measurements of airway structure correlated with airway function.. airway structure| high-resolution computed tomography| lung disease|thin-section ct| pulmonary-function| wall thickness| young-children| lung-disease| acute exacerbation| scoring system| asthma| inflammation| emphysema.	NOV 1-2005	airway structure| high-resolution computed tomography| lung disease|thin-section ct| pulmonary-function| wall thickness| young-children| lung-disease| acute exacerbation| scoring system| asthma| inflammation| emphysema	Martinez, TM; Llapur, CJ; Williams, TH; Coates, C; Gunderman, R; Cohen, MD; Howenstine, MS; Saba, O; Coxson, HO; Tepper, RS	High-resolution computed tomography imaging of airway disease in infants with cystic fibrosis		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	airway structure; high-resolution computed tomography; lung disease	THIN-SECTION CT; PULMONARY-FUNCTION; WALL THICKNESS; YOUNG-CHILDREN; LUNG-DISEASE; ACUTE EXACERBATION; SCORING SYSTEM; ASTHMA; INFLAMMATION; EMPHYSEMA	Rationale: The development of early lung disease in patients with cystic fibrosis (CF) remains poorly defined. Objective: Determine whether asymptomatic infants with CF have evidence for changes in airway structure when assessed by high-resolution computed tomography, and whether airway structure correlates with airway function in this age group. Methods: Thirteen infants with CF (8-33 mo) and 13 control infants (7-25 mo) were evaluated. Airway wall and lumen areas were measured from three 1-mm-thick cross-sectional images obtained from upper, middle, and lower lobes during a respiratory pause with the lungs inflated to an airway pressure of 20 cm H2O. Lung tissue density was measured from images obtained during a respiratory pause at FRC. Forced expiratory flows were measured by the rapid thoracic compression technique in 11 infants with CF. Results: Airway wall area increased more per unit increase in airway size, whereas airway lumen area increased less per unit increase in airway size in the CF than in the control group. Among infants with CF, a greater ratio of wall to lumen area correlated with lower airway function. In addition, lung density at relaxed (passive) FRC was lower for infants with Cl: than for control infants (0.38 vs. 0.43 g/ml; p < 0.02). Conclusions: Our results indicate that infants with CF have thickened airway walls, narrowed airway lumens, and air trapping, when assessed by high-resolution computed tomography, and measurements of airway structure correlated with airway function.	47	78	2005	6	10.1164/rccm.200412-1665OC	General & Internal Medicine; Respiratory System
Chronic exposure to ambient ozone and lung function in young adults. Background: Tropospheric ozone (O-3) is an oxidant, outdoor air pollutant. Chronic exposure has been associated with decreased lung function in children and adolescents. This study investigated the effects of long-term exposure to O-3 on lung function in college freshmen. Methods: We recruited University of California, Berkeley students (n = 255) who were lifelong residents of the Los Angeles and San Francisco Bay areas and who never smoked. Lifetime exposures to O-3, small particulate matter (PM10), and nitrogen dioxide (NO2) were based on spatial interpolation of compliance monitor measurements to all residences at which students lived. Spirometry was performed between February and May, times when students would not have had recent exposure to increased levels of O-3. Results: Lifetime exposure to O-3 was associated with decreased levels of measures of small airways ( < 2 mm) function (FEF75 and FEF25-75). There was an interaction with the FEF25-75/FVC ratio, a measure of intrinsic airway size. Subjects with a large ratio were less likely to have decreases in FEF75 and FEF25-75 for a given estimated lifetime exposure to O-3. This association was not altered by history of chronic respiratory disease, allergy, second-hand exposure to environmental tobacco smoke, exposure to PM10 and NO2, or measurement errors in exposure assessment. Conclusions: A history of increased level of lifetime exposure to ambient O-3 is associated with decreased function of airways in which O-3 deposition in the lungs is the greatest. Adolescents with intrinsically smaller airways appear to be at greatest risk. Any environmental or genetic factors that lead to reduced airway size may lead to increased susceptibility to the adverse effects of ambient ozone.. air-pollution| long-term| pulmonary-function| nitrogen-dioxide| children| association| asthma| pollutants| california| mortality.	NOV-2005	air-pollution| long-term| pulmonary-function| nitrogen-dioxide| children| association| asthma| pollutants| california| mortality	Tager, IB; Balmes, J; Lurmann, F; Ngo, L; Alcorn, S; Kunzli, N	Chronic exposure to ambient ozone and lung function in young adults		EPIDEMIOLOGY		AIR-POLLUTION; LONG-TERM; PULMONARY-FUNCTION; NITROGEN-DIOXIDE; CHILDREN; ASSOCIATION; ASTHMA; POLLUTANTS; CALIFORNIA; MORTALITY	Background: Tropospheric ozone (O-3) is an oxidant, outdoor air pollutant. Chronic exposure has been associated with decreased lung function in children and adolescents. This study investigated the effects of long-term exposure to O-3 on lung function in college freshmen. Methods: We recruited University of California, Berkeley students (n = 255) who were lifelong residents of the Los Angeles and San Francisco Bay areas and who never smoked. Lifetime exposures to O-3, small particulate matter (PM10), and nitrogen dioxide (NO2) were based on spatial interpolation of compliance monitor measurements to all residences at which students lived. Spirometry was performed between February and May, times when students would not have had recent exposure to increased levels of O-3. Results: Lifetime exposure to O-3 was associated with decreased levels of measures of small airways ( < 2 mm) function (FEF75 and FEF25-75). There was an interaction with the FEF25-75/FVC ratio, a measure of intrinsic airway size. Subjects with a large ratio were less likely to have decreases in FEF75 and FEF25-75 for a given estimated lifetime exposure to O-3. This association was not altered by history of chronic respiratory disease, allergy, second-hand exposure to environmental tobacco smoke, exposure to PM10 and NO2, or measurement errors in exposure assessment. Conclusions: A history of increased level of lifetime exposure to ambient O-3 is associated with decreased function of airways in which O-3 deposition in the lungs is the greatest. Adolescents with intrinsically smaller airways appear to be at greatest risk. Any environmental or genetic factors that lead to reduced airway size may lead to increased susceptibility to the adverse effects of ambient ozone.	58	78	2005	9	10.1097/01.ede.0000183166.68809.b0	Public, Environmental & Occupational Health
Multiple impacts of the built environment on public health: Walkable places and the exposure to air pollution. While considerable attention has been paid to the public-health-related impacts of air pollution, relatively little research has been done to understand how other aspects of the built environment impact health. Americans are increasingly sedentary; erstwhile the rate of increase in obesity is alarming. New research suggests that increased auto dependence, and limited opportunities to walk for utilitarian purposes, has contributed to this emerging obesity, epidemic. Within socio-demographic strata, land use patterns and transportation investments collectively shape the desire to walk, drive, or to travel via other means. Mixed use and more compact community designs show significant promise for the promotion of physical activity and the reduction of regional air pollution levels. Opportunities exist to increase physical activity and improve regional air quality through more compact development. However, increased compactness, or density, often exacerbates traffic congestion and can increase exposure of harmful emissions within central areas. Therefore, strategies to reduce localized air pollution in existing and developing centers are required to enable larger health benefits from smart growth to be realized.. physical activity| air quality| built environment| travel behavior|physical-activity| urban form| land-use| myocardial-infarction| childhood asthma| transportation| quality| mortality| walking| atlanta.	APR-2005	physical activity| air quality| built environment| travel behavior|physical-activity| urban form| land-use| myocardial-infarction| childhood asthma| transportation| quality| mortality| walking| atlanta	Frank, LD; Engelke, P	Multiple impacts of the built environment on public health: Walkable places and the exposure to air pollution		INTERNATIONAL REGIONAL SCIENCE REVIEW	physical activity; air quality; built environment; travel behavior	PHYSICAL-ACTIVITY; URBAN FORM; LAND-USE; MYOCARDIAL-INFARCTION; CHILDHOOD ASTHMA; TRANSPORTATION; QUALITY; MORTALITY; WALKING; ATLANTA	While considerable attention has been paid to the public-health-related impacts of air pollution, relatively little research has been done to understand how other aspects of the built environment impact health. Americans are increasingly sedentary; erstwhile the rate of increase in obesity is alarming. New research suggests that increased auto dependence, and limited opportunities to walk for utilitarian purposes, has contributed to this emerging obesity, epidemic. Within socio-demographic strata, land use patterns and transportation investments collectively shape the desire to walk, drive, or to travel via other means. Mixed use and more compact community designs show significant promise for the promotion of physical activity and the reduction of regional air pollution levels. Opportunities exist to increase physical activity and improve regional air quality through more compact development. However, increased compactness, or density, often exacerbates traffic congestion and can increase exposure of harmful emissions within central areas. Therefore, strategies to reduce localized air pollution in existing and developing centers are required to enable larger health benefits from smart growth to be realized.	81	78	2005	24	10.1177/0160017604273853	Environmental Sciences & Ecology; Public Administration; Urban Studies
Endotoxin exposure and atopic sensitization in adult pig farmers. Background: Recent studies have reported a low prevalence of atopic sensitization and respiratory allergy in children growing up on farms. Objectives: We sought to evaluate the dose-response relationship between endotoxin and atopic sensitization in adult farmers and to assess the effect on respiratory health outcomes. Methods: Data on endotoxin exposure and serum IgE levels were available for 162 pig farmers from a cross-sectional, case-control study, with case selection on the basis of respiratory symptoms. Exposure to endotoxin was modeled in detail, and respiratory health effects were assessed during a medical examination. Exploratory analysis was done by using nonparametric modeling and was followed by classical parametric regression. Results: IgE to one or more common allergens was detected in sera from 28 (17%) farmers. The average (geometric mean) total serum IgE levels was 37 lU/mL (geometric SD, 4 IU/mL). A strong inverse relationship was found between endotoxin and sensitization to common allergens for exposures of 75 ng/m(3) or less, with an odds ratio of 0.03 (95% CI, 0.0-0.34) for a 2-fold increase in endotoxin. For endotoxin exposure of greater than 75 ng/m(3), the association was weak (odds ratio, 1.2 [95% Cl, 0.38-3.6]). No association was found between endotoxin exposure and total serum IgE levels. Endotoxin was associated with increased airway hyperresponsiveness to histamine and lower lung function in sensitized farmers, without evidence of a nonlinear relationship. Conclusions: The prevalence of atopic sensitization in adult pig farmers is low. Endotoxin or related exposures might protect from sensitization, even in an adult working population exposed to high levels of endotoxin, but is a risk factor for increased airway hyperresponsiveness and low lung function.. endotoxins| hypersensitivity| ige| allergens| adult| occupational exposure| epidemiology|respiratory symptoms| bronchial hyperresponsiveness| allergic sensitization| lung-function| house-dust| asthma| children| population| childhood| environment.	APR-2005	endotoxins| hypersensitivity| ige| allergens| adult| occupational exposure| epidemiology|respiratory symptoms| bronchial hyperresponsiveness| allergic sensitization| lung-function| house-dust| asthma| children| population| childhood| environment	Portengen, L; Preller, L; Tielen, M; Doekes, G; Heederik, D	Endotoxin exposure and atopic sensitization in adult pig farmers		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	endotoxins; hypersensitivity; IgE; allergens; adult; occupational exposure; epidemiology	RESPIRATORY SYMPTOMS; BRONCHIAL HYPERRESPONSIVENESS; ALLERGIC SENSITIZATION; LUNG-FUNCTION; HOUSE-DUST; ASTHMA; CHILDREN; POPULATION; CHILDHOOD; ENVIRONMENT	Background: Recent studies have reported a low prevalence of atopic sensitization and respiratory allergy in children growing up on farms. Objectives: We sought to evaluate the dose-response relationship between endotoxin and atopic sensitization in adult farmers and to assess the effect on respiratory health outcomes. Methods: Data on endotoxin exposure and serum IgE levels were available for 162 pig farmers from a cross-sectional, case-control study, with case selection on the basis of respiratory symptoms. Exposure to endotoxin was modeled in detail, and respiratory health effects were assessed during a medical examination. Exploratory analysis was done by using nonparametric modeling and was followed by classical parametric regression. Results: IgE to one or more common allergens was detected in sera from 28 (17%) farmers. The average (geometric mean) total serum IgE levels was 37 lU/mL (geometric SD, 4 IU/mL). A strong inverse relationship was found between endotoxin and sensitization to common allergens for exposures of 75 ng/m(3) or less, with an odds ratio of 0.03 (95% CI, 0.0-0.34) for a 2-fold increase in endotoxin. For endotoxin exposure of greater than 75 ng/m(3), the association was weak (odds ratio, 1.2 [95% Cl, 0.38-3.6]). No association was found between endotoxin exposure and total serum IgE levels. Endotoxin was associated with increased airway hyperresponsiveness to histamine and lower lung function in sensitized farmers, without evidence of a nonlinear relationship. Conclusions: The prevalence of atopic sensitization in adult pig farmers is low. Endotoxin or related exposures might protect from sensitization, even in an adult working population exposed to high levels of endotoxin, but is a risk factor for increased airway hyperresponsiveness and low lung function.	41	78	2005	6	10.1016/j.jaci.2004.11.046	Allergy; Immunology
Health disparities and gaps in school readiness. The author documents pervasive racial disparities in the health of American children and analyzes how and how much those disparities contribute to racial gaps in school readiness. She explores a broad sample of health problems common to U.S. children, such as attention deficit hyperactivity disorder, asthma, and lead poisoning, as well as maternal health problems and health-related behaviors that affect children's behavioral and cognitive readiness for school. If a health problem is to affect the readiness gap, it must affect many children, it must be linked to academic performance or behavior problems, and it must show a racial disparity either in its prevalence or in its effects. The author focuses not only on the black-white gap in health status but also on the poor-nonpoor gap because black children tend to be poorer than white children. The health conditions Currie considers seriously impair cognitive skills and behavior in individual children. But most explain little of the overall racial gap in school readiness. Still, the cumulative effect of health differentials summed over all conditions is significant. Curries rough calculation is that racial differences in health conditions and in maternal health and behaviors together may account for as much as a quarter of the racial gap in school readiness. Currie scrutinizes several policy steps to lessen racial and socioeconomic disparities in children's health and to begin to close the readiness gap. Increasing poor children's eligibility for Medicaid and state child health insurance is unlikely to be effective because most poor children are already eligible for public insurance. The problem is that many are not enrolled. Even increasing enrollment may not work: socioeconomic disparities in health persist in Canada and the United Kingdom despite universal public health insurance. The author finds more promise in strengthening early childhood programs with a built-in health component, like Head Start; family-based services and home visiting programs; and WIC, the federal nutrition program for women. infants, and small children. In all three, trained staff can help parents get ongoing care for their children.. united-states| cognitive-development| maternal depression| postnatal depression| behavior problems| childhood asthma| iron-deficiency| young-children| primary-care| lead levels.	SPR-2005	united-states| cognitive-development| maternal depression| postnatal depression| behavior problems| childhood asthma| iron-deficiency| young-children| primary-care| lead levels	Currie, J	Health disparities and gaps in school readiness		FUTURE OF CHILDREN		UNITED-STATES; COGNITIVE-DEVELOPMENT; MATERNAL DEPRESSION; POSTNATAL DEPRESSION; BEHAVIOR PROBLEMS; CHILDHOOD ASTHMA; IRON-DEFICIENCY; YOUNG-CHILDREN; PRIMARY-CARE; LEAD LEVELS	The author documents pervasive racial disparities in the health of American children and analyzes how and how much those disparities contribute to racial gaps in school readiness. She explores a broad sample of health problems common to U.S. children, such as attention deficit hyperactivity disorder, asthma, and lead poisoning, as well as maternal health problems and health-related behaviors that affect children's behavioral and cognitive readiness for school. If a health problem is to affect the readiness gap, it must affect many children, it must be linked to academic performance or behavior problems, and it must show a racial disparity either in its prevalence or in its effects. The author focuses not only on the black-white gap in health status but also on the poor-nonpoor gap because black children tend to be poorer than white children. The health conditions Currie considers seriously impair cognitive skills and behavior in individual children. But most explain little of the overall racial gap in school readiness. Still, the cumulative effect of health differentials summed over all conditions is significant. Curries rough calculation is that racial differences in health conditions and in maternal health and behaviors together may account for as much as a quarter of the racial gap in school readiness. Currie scrutinizes several policy steps to lessen racial and socioeconomic disparities in children's health and to begin to close the readiness gap. Increasing poor children's eligibility for Medicaid and state child health insurance is unlikely to be effective because most poor children are already eligible for public insurance. The problem is that many are not enrolled. Even increasing enrollment may not work: socioeconomic disparities in health persist in Canada and the United Kingdom despite universal public health insurance. The author finds more promise in strengthening early childhood programs with a built-in health component, like Head Start; family-based services and home visiting programs; and WIC, the federal nutrition program for women. infants, and small children. In all three, trained staff can help parents get ongoing care for their children.	75	78	2005	22	10.1353/foc.2005.0002	Family Studies; Health Care Sciences & Services; Social Sciences - Other Topics
Chemoattractants and their receptors in homeostasis and inflammation. The study of leukocyte migration continues to provide new insights into the regulation of lymphocyte priming in secondary lymphoid organs and effector responses in inflamed tissues. Chemoattractant receptors have always been viewed as facilitators of cell movement into a tissue. This whole concept must now be revised with the discovery of sphingosine 1 phosphate receptors, which control cell exit from lymphoid tissues. The chemoattractants that regulate lymphoid tissue homing are usually different to those that regulate leukocyte recruitment to inflamed tissues. There is evidence, however, of inflammatory pathways of leukocyte recruitment in lymph nodes and, conversely of constitutive pathways in peripheral tissues. Finally, antagonists (or agonists) of chemoattractant receptors and their signalling pathways represent the most attractive strategy for the treatment of a wide range of inflammatory diseases, including allergy.. leukotriene b-4 receptor| naive t-cells| protein-coupled receptor| allergic airway disease| dendritic cells| lymph-nodes| sphingosine 1-phosphate| chemokine receptors| chemotactic responsiveness| eosinophil recruitment.	DEC-2004	leukotriene b-4 receptor| naive t-cells| protein-coupled receptor| allergic airway disease| dendritic cells| lymph-nodes| sphingosine 1-phosphate| chemokine receptors| chemotactic responsiveness| eosinophil recruitment	Sallusto, F; Mackay, CR	Chemoattractants and their receptors in homeostasis and inflammation		CURRENT OPINION IN IMMUNOLOGY		LEUKOTRIENE B-4 RECEPTOR; NAIVE T-CELLS; PROTEIN-COUPLED RECEPTOR; ALLERGIC AIRWAY DISEASE; DENDRITIC CELLS; LYMPH-NODES; SPHINGOSINE 1-PHOSPHATE; CHEMOKINE RECEPTORS; CHEMOTACTIC RESPONSIVENESS; EOSINOPHIL RECRUITMENT	The study of leukocyte migration continues to provide new insights into the regulation of lymphocyte priming in secondary lymphoid organs and effector responses in inflamed tissues. Chemoattractant receptors have always been viewed as facilitators of cell movement into a tissue. This whole concept must now be revised with the discovery of sphingosine 1 phosphate receptors, which control cell exit from lymphoid tissues. The chemoattractants that regulate lymphoid tissue homing are usually different to those that regulate leukocyte recruitment to inflamed tissues. There is evidence, however, of inflammatory pathways of leukocyte recruitment in lymph nodes and, conversely of constitutive pathways in peripheral tissues. Finally, antagonists (or agonists) of chemoattractant receptors and their signalling pathways represent the most attractive strategy for the treatment of a wide range of inflammatory diseases, including allergy.	78	78	2004	8	10.1016/j.coi.2004.09.012	Immunology
The Canadian asthma primary prevention study: Outcomes at 2 years of age. Background: Avoidance of individual risk factors have not been successful in preventing the development of asthma. Objective: We sought to determine the effectiveness of a multifaceted intervention program in primary prevention of asthma in high-risk infants. Methods: We identified 545 high-risk infants on the basis of an immediate family history of asthma. Families were randomized into intervention or control groups. Intervention measures included avoidance of house dust mite, pet allergen, and environmental tobacco smoke. Breast-feeding was encouraged with formula supplementation if necessary, and introduction of solid foods was delayed. Results: At 2 years of age, 19.5% of the children had asthma, and 14.7% had atopy (positive skin test response to one or more common allergens). Significantly fewer children had asthma in the intervention group compared with in the control group (16.3% vs 23.0%), with 60% less persistent asthma at 2 years. There was a 90% reduction for recurrent wheeze in the intervention group compared with that seen in the control group. Exposure to maternal environmental tobacco smoke during pregnancy or the first year was a risk factor for asthma at 2 years of age. A positive skin test response, particularly to food, at 12 months predicted asthma at 2 years. There was no significant difference for atopy between the intervention and control groups, but daycare reduced atopy at 2 years. Conclusion: This multifaceted intervention program during a window of opportunity in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important.. asthma| atopy| risk factors| primary prevention| environmental tobacco smoke| daycare| breast-feeding| early life|cat allergen levels| childhood asthma| house-dust| early-life| mite allergen| birth cohort| risk-factors| p-i| avoidance| exposure.	APR-2004	asthma| atopy| risk factors| primary prevention| environmental tobacco smoke| daycare| breast-feeding| early life|cat allergen levels| childhood asthma| house-dust| early-life| mite allergen| birth cohort| risk-factors| p-i| avoidance| exposure	Becker, A; Watson, W; Ferguson, A; Dimich-Ward, H; Chan-Yeung, M	The Canadian asthma primary prevention study: Outcomes at 2 years of age		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; atopy; risk factors; primary prevention; environmental tobacco smoke; daycare; breast-feeding; early life	CAT ALLERGEN LEVELS; CHILDHOOD ASTHMA; HOUSE-DUST; EARLY-LIFE; MITE ALLERGEN; BIRTH COHORT; RISK-FACTORS; P-I; AVOIDANCE; EXPOSURE	Background: Avoidance of individual risk factors have not been successful in preventing the development of asthma. Objective: We sought to determine the effectiveness of a multifaceted intervention program in primary prevention of asthma in high-risk infants. Methods: We identified 545 high-risk infants on the basis of an immediate family history of asthma. Families were randomized into intervention or control groups. Intervention measures included avoidance of house dust mite, pet allergen, and environmental tobacco smoke. Breast-feeding was encouraged with formula supplementation if necessary, and introduction of solid foods was delayed. Results: At 2 years of age, 19.5% of the children had asthma, and 14.7% had atopy (positive skin test response to one or more common allergens). Significantly fewer children had asthma in the intervention group compared with in the control group (16.3% vs 23.0%), with 60% less persistent asthma at 2 years. There was a 90% reduction for recurrent wheeze in the intervention group compared with that seen in the control group. Exposure to maternal environmental tobacco smoke during pregnancy or the first year was a risk factor for asthma at 2 years of age. A positive skin test response, particularly to food, at 12 months predicted asthma at 2 years. There was no significant difference for atopy between the intervention and control groups, but daycare reduced atopy at 2 years. Conclusion: This multifaceted intervention program during a window of opportunity in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important.	38	78	2004	7	10.1016/j.jaci.2004.01.754	Allergy; Immunology
Trends in otitis media among children in the United States. Background. The prevalence of repeated otitis media ( OM) increased during the 1980s, but it is unknown if the increase has continued. Objectives. To determine trends in the prevalence of OM, early-onset OM, and repeated OM among US children from 1988 to 1994 and to identify factors that may explain any observed changes. Methods. The Third National Health and Nutrition Examination Survey was administered in 2 phases: phase I ( 1988 - 1991) and phase II ( 1991 - 1994), each comprising a national probability sample. OM ( ever having had OM), early-onset OM ( first episode at < 12 months of age), and repeated OM (&GE; 3 episodes) were assessed for 8261 children < 6 years of age. Results. After controlling for risk factors for OM, the prevalence of OM from phase I to phase II increased from 66.7% to 69.7% ( odds ratio [ OR] = 1.1; 95% confidence interval [ CI] = .99, 1.1), early-onset OM increased from 41.1% to 45.8% ( OR = 1.1; 95% CI = 1.03, 1.2), and repeated OM increased from 34.8% to 41.1% ( OR = 1.2; 95% CI = 1.1, 1.4). This observed increase corresponds to 561 000 and 720 000 more children having early-onset OM and repeated OM, respectively. Child care use, early breastfeeding termination, asthma, and access to health care did not significantly increase from phase I to phase II. The prevalence of early-onset OM and repeated OM was higher for affluent children, but the greatest increase in prevalence was among impoverished children. There was an increase in allergic conditions from phase I to phase II for poor children (22.6% to 30.2%). Conclusions. The prevalence of early-onset OM and repeated OM continued to increase among preschool children in the United States. Further research to investigate this increasing prevalence should explore changes in management practice and an increase in prevalence of allergic conditions among poor children.. otitis media| early-onset otitis media| national health and nutrition examination survey| allergy| epidemiology| pediatric| children|passive smoke exposure| middle-ear disease| risk-factors| young-children| life| asthma| prevalence| infections| outcomes| vaccine.	SEP-2003	otitis media| early-onset otitis media| national health and nutrition examination survey| allergy| epidemiology| pediatric| children|passive smoke exposure| middle-ear disease| risk-factors| young-children| life| asthma| prevalence| infections| outcomes| vaccine	Auinger, P; Lanphear, BP; Kalkwarf, HJ; Mansour, ME	Trends in otitis media among children in the United States		PEDIATRICS	otitis media; early-onset otitis media; National Health and Nutrition Examination Survey; allergy; epidemiology; pediatric; children	PASSIVE SMOKE EXPOSURE; MIDDLE-EAR DISEASE; RISK-FACTORS; YOUNG-CHILDREN; LIFE; ASTHMA; PREVALENCE; INFECTIONS; OUTCOMES; VACCINE	Background. The prevalence of repeated otitis media ( OM) increased during the 1980s, but it is unknown if the increase has continued. Objectives. To determine trends in the prevalence of OM, early-onset OM, and repeated OM among US children from 1988 to 1994 and to identify factors that may explain any observed changes. Methods. The Third National Health and Nutrition Examination Survey was administered in 2 phases: phase I ( 1988 - 1991) and phase II ( 1991 - 1994), each comprising a national probability sample. OM ( ever having had OM), early-onset OM ( first episode at < 12 months of age), and repeated OM (&GE; 3 episodes) were assessed for 8261 children < 6 years of age. Results. After controlling for risk factors for OM, the prevalence of OM from phase I to phase II increased from 66.7% to 69.7% ( odds ratio [ OR] = 1.1; 95% confidence interval [ CI] = .99, 1.1), early-onset OM increased from 41.1% to 45.8% ( OR = 1.1; 95% CI = 1.03, 1.2), and repeated OM increased from 34.8% to 41.1% ( OR = 1.2; 95% CI = 1.1, 1.4). This observed increase corresponds to 561 000 and 720 000 more children having early-onset OM and repeated OM, respectively. Child care use, early breastfeeding termination, asthma, and access to health care did not significantly increase from phase I to phase II. The prevalence of early-onset OM and repeated OM was higher for affluent children, but the greatest increase in prevalence was among impoverished children. There was an increase in allergic conditions from phase I to phase II for poor children (22.6% to 30.2%). Conclusions. The prevalence of early-onset OM and repeated OM continued to increase among preschool children in the United States. Further research to investigate this increasing prevalence should explore changes in management practice and an increase in prevalence of allergic conditions among poor children.	44	78	2003	7	10.1542/peds.112.3.514	Pediatrics
Effect of two breathing exercises (Buteyko and pranayama) in asthma: a randomised controlled trial. Background: Patients with asthma are interested in the use of breathing exercises but their role is uncertain. The effects of the Buteyko breathing technique, a device which mimics pranayama (a yoga breathing technique), and a dummy pranayama device on bronchial responsiveness and symptoms were compared over 6 months in a parallel group study. Methods: Ninety patients with asthma taking an inhaled corticosteroid were randomised after a 2 week run in period to Eucapnic Buteyko breathing, use of a Pink City Lung Exerciser (PCLE) to mimic pranayama, or a PCLE placebo device. Subjects practised the techniques at home twice daily for 6 months followed by an optional steroid reduction phase. Primary outcome measures were symptom scores and change in the dose of methacholine provoking a 20% fall in FEV1 (PD20) during the first 6 months. Results: Sixty nine patients (78%) completed the study. There was no significant difference in PD20 between the three groups at 3 or 6 months. Symptoms remained relatively stable in the PCLE and placebo groups but were reduced in the Buteyko group. Median change in symptom scores at 6 months was 0 (interquartile range -1 to 1) in the placebo group, -1 (-2 to 0.75) in the PCLE group, and -3 (-4 to 0) in the Buteyko group (p=0.003 for difference between groups). Bronchodilator use was reduced in the Buteyko group by two puffs/day at 6 months; there was no change in the other two groups (p=0.005). No difference was seen between the groups in FEV1, exacerbations, or ability to reduce inhaled corticosteroids. Conclusion: The Buteyko breathing technique can improve symptoms and reduce bronchodilator use but does not appear to change bronchial responsiveness or lung function in patients with asthma. No benefit was shown for the Pink City Lung Exerciser.. alternative medicine| yoga.	AUG-2003	alternative medicine| yoga	Cooper, S; Oborne, J; Newton, S; Harrison, V; Coon, JT; Lewis, S; Tattersfield, A	Effect of two breathing exercises (Buteyko and pranayama) in asthma: a randomised controlled trial		THORAX		ALTERNATIVE MEDICINE; YOGA	Background: Patients with asthma are interested in the use of breathing exercises but their role is uncertain. The effects of the Buteyko breathing technique, a device which mimics pranayama (a yoga breathing technique), and a dummy pranayama device on bronchial responsiveness and symptoms were compared over 6 months in a parallel group study. Methods: Ninety patients with asthma taking an inhaled corticosteroid were randomised after a 2 week run in period to Eucapnic Buteyko breathing, use of a Pink City Lung Exerciser (PCLE) to mimic pranayama, or a PCLE placebo device. Subjects practised the techniques at home twice daily for 6 months followed by an optional steroid reduction phase. Primary outcome measures were symptom scores and change in the dose of methacholine provoking a 20% fall in FEV1 (PD20) during the first 6 months. Results: Sixty nine patients (78%) completed the study. There was no significant difference in PD20 between the three groups at 3 or 6 months. Symptoms remained relatively stable in the PCLE and placebo groups but were reduced in the Buteyko group. Median change in symptom scores at 6 months was 0 (interquartile range -1 to 1) in the placebo group, -1 (-2 to 0.75) in the PCLE group, and -3 (-4 to 0) in the Buteyko group (p=0.003 for difference between groups). Bronchodilator use was reduced in the Buteyko group by two puffs/day at 6 months; there was no change in the other two groups (p=0.005). No difference was seen between the groups in FEV1, exacerbations, or ability to reduce inhaled corticosteroids. Conclusion: The Buteyko breathing technique can improve symptoms and reduce bronchodilator use but does not appear to change bronchial responsiveness or lung function in patients with asthma. No benefit was shown for the Pink City Lung Exerciser.	15	78	2003	6	10.1136/thorax.58.8.674	Respiratory System
Cleaning products and work-related asthma. To describe the characteristics of individuals with work-related asthma associated with exposure to cleaning products, data from the California-, Massachusetts-, Michigan-, and New Jersey state-based surveillance systems of work-related asthma were used to identify cases of asthma associated with exposure to cleaning products at work. From 1993 to 1997, 236 (12 %) of the 1915 confirmed cases of work-related asthma identfied by the four states were associated with exposure to cleaning products. Eighty Percent of the reports were of new-onset asthma and 20% were work-aggravated asthma. Among the new-onset cases, 22 % were consistent with reactive airways dysfunction syndrome. Individuals identfied were generally women (75 %), white non-Hispanic (68 %), and 45 years or older (64 %). Their most likely exposure had been in medical settings (39 %), schools (13 %), or hotels (6 %), and they were most likely to work as janitor/cleaners (22 %), nurse/nurses' aides (20 %), or clerical staff (13 %). However, cases were reported with exposure to cleaning products across a wide range of job titles. Cleaning products contain a diverse group of chemicals that are used in a wide range of industries and occupations as well as in the home. Their potential to cause or aggravate asthma has recently been recognized. Further work to characterize the specific agents and the circumstances of their use associated with asthma is needed. Additional research to investigate the frequency of adverse respiratory effects among regular users, such as housekeeping staff, is also needed. In the interim, we recommend attention to adequate ventilation, improved warning labels and Material Safety Data Sheets, and workplace training and education.. occupational asthma| surveillance system| exposure| cleaners.	MAY-2003	occupational asthma| surveillance system| exposure| cleaners	Rosenman, KD; Reilly, MJ; Schill, DP; Valiante, D; Flattery, J; Harrison, R; Reinisch, F; Pechter, E; Davis, L; Tumpowsky, CM; Filios, M	Cleaning products and work-related asthma		JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		OCCUPATIONAL ASTHMA; SURVEILLANCE SYSTEM; EXPOSURE; CLEANERS	To describe the characteristics of individuals with work-related asthma associated with exposure to cleaning products, data from the California-, Massachusetts-, Michigan-, and New Jersey state-based surveillance systems of work-related asthma were used to identify cases of asthma associated with exposure to cleaning products at work. From 1993 to 1997, 236 (12 %) of the 1915 confirmed cases of work-related asthma identfied by the four states were associated with exposure to cleaning products. Eighty Percent of the reports were of new-onset asthma and 20% were work-aggravated asthma. Among the new-onset cases, 22 % were consistent with reactive airways dysfunction syndrome. Individuals identfied were generally women (75 %), white non-Hispanic (68 %), and 45 years or older (64 %). Their most likely exposure had been in medical settings (39 %), schools (13 %), or hotels (6 %), and they were most likely to work as janitor/cleaners (22 %), nurse/nurses' aides (20 %), or clerical staff (13 %). However, cases were reported with exposure to cleaning products across a wide range of job titles. Cleaning products contain a diverse group of chemicals that are used in a wide range of industries and occupations as well as in the home. Their potential to cause or aggravate asthma has recently been recognized. Further work to characterize the specific agents and the circumstances of their use associated with asthma is needed. Additional research to investigate the frequency of adverse respiratory effects among regular users, such as housekeeping staff, is also needed. In the interim, we recommend attention to adequate ventilation, improved warning labels and Material Safety Data Sheets, and workplace training and education.	32	78	2003	8	10.1097/01.jom.0000058347.05741.f9	Public, Environmental & Occupational Health
Tear and mucus eotaxin-l and eotaxin-2 in allergic keratoconjunctivitis. Objective: Eotaxin-1 and eotaxin-2 are potent eosinophil chemotactic and activating peptides that may be implicated in the pathogenesis of the chronic allergic eye diseases vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). The purpose of this study was to measure these chemokines, in tear and mucus samples of active-disease patients and in vitro cultured conjunctival epithelial cells and fibroblasts. Design: Comparative, observational case series and in vitro study. Participants: Sixteen patients with clinically active and untreated VKC or AKC, six age-matched control patients, and five nonactive seasonal allergic conjunctivitis patients. Methods: Tears were collected from the active VKC and AKC patients, and from the normal patients. Mucus was collected from six of these VKC patients. Tears were also collected from an additional five allergic patients after obtaining a positive reaction to conjunctival allergen challenge. Conjunctival epithelial cell and conjunctival fibroblast cultures were exposed to interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-alpha), or to combinations of these cytokines. Main Outcome Measures: Levels of eotaxin-1 and eotaxin-2 in tears, mucus, and culture medium. Results: High levels of eotaxin-1 and eotaxin-2 were found in mucus of VKC patients, whereas only eotaxin-2 was found to have increased significantly in tears of VKC and AKC patients compared with those of normal patients. Mucus contained higher levels of chemokines than did tears. Both tear eotaxin-1 and eotaxin-2 were correlated significantly with the percent of eosinophils in tear fluid. Eotaxin-1 also was correlated significantly with the sum clinical score and corneal involvement in VKC patients. Conjunctival epithelial cells in culture did not produce eotaxin-1 or eotaxin-2, either at baseline or after cytokine exposure. Conjunctival fibroblasts produced eotaxin-1 only after exposure to IL-4, TNF-alpha, and the combination of IL-4 plus TNF-alpha or IL-13 plus TNF-alpha. Conclusions: Eotaxin-1 and eotaxin-2 are implicated in eosinophil recruitment and in the pathogenesis of VKC and AKC. Cytokine-stimulated conjunctival fibroblasts may be one source of eotaxin-1 in severely allergic tissues. (C) 2003 by the American Academy of Ophthalmology.. il-4 induces eotaxin| vernal keratoconjunctivitis| atopic keratoconjunctivitis| conjunctival fibroblasts| human eosinophil| messenger-rna| eye disease| tnf-alpha| in-vitro| expression.	MAR-2003	il-4 induces eotaxin| vernal keratoconjunctivitis| atopic keratoconjunctivitis| conjunctival fibroblasts| human eosinophil| messenger-rna| eye disease| tnf-alpha| in-vitro| expression	Leonardi, A; Jose, PJ; Zhan, H; Calder, VL	Tear and mucus eotaxin-l and eotaxin-2 in allergic keratoconjunctivitis		OPHTHALMOLOGY		IL-4 INDUCES EOTAXIN; VERNAL KERATOCONJUNCTIVITIS; ATOPIC KERATOCONJUNCTIVITIS; CONJUNCTIVAL FIBROBLASTS; HUMAN EOSINOPHIL; MESSENGER-RNA; EYE DISEASE; TNF-ALPHA; IN-VITRO; EXPRESSION	Objective: Eotaxin-1 and eotaxin-2 are potent eosinophil chemotactic and activating peptides that may be implicated in the pathogenesis of the chronic allergic eye diseases vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). The purpose of this study was to measure these chemokines, in tear and mucus samples of active-disease patients and in vitro cultured conjunctival epithelial cells and fibroblasts. Design: Comparative, observational case series and in vitro study. Participants: Sixteen patients with clinically active and untreated VKC or AKC, six age-matched control patients, and five nonactive seasonal allergic conjunctivitis patients. Methods: Tears were collected from the active VKC and AKC patients, and from the normal patients. Mucus was collected from six of these VKC patients. Tears were also collected from an additional five allergic patients after obtaining a positive reaction to conjunctival allergen challenge. Conjunctival epithelial cell and conjunctival fibroblast cultures were exposed to interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-alpha), or to combinations of these cytokines. Main Outcome Measures: Levels of eotaxin-1 and eotaxin-2 in tears, mucus, and culture medium. Results: High levels of eotaxin-1 and eotaxin-2 were found in mucus of VKC patients, whereas only eotaxin-2 was found to have increased significantly in tears of VKC and AKC patients compared with those of normal patients. Mucus contained higher levels of chemokines than did tears. Both tear eotaxin-1 and eotaxin-2 were correlated significantly with the percent of eosinophils in tear fluid. Eotaxin-1 also was correlated significantly with the sum clinical score and corneal involvement in VKC patients. Conjunctival epithelial cells in culture did not produce eotaxin-1 or eotaxin-2, either at baseline or after cytokine exposure. Conjunctival fibroblasts produced eotaxin-1 only after exposure to IL-4, TNF-alpha, and the combination of IL-4 plus TNF-alpha or IL-13 plus TNF-alpha. Conclusions: Eotaxin-1 and eotaxin-2 are implicated in eosinophil recruitment and in the pathogenesis of VKC and AKC. Cytokine-stimulated conjunctival fibroblasts may be one source of eotaxin-1 in severely allergic tissues. (C) 2003 by the American Academy of Ophthalmology.	30	78	2003	6	10.1016/S0161-6420(02)01767-0	Ophthalmology
Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit. Background: Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). Objective: We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. Methods: In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. Results: Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P < .02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P less than or equal to .003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P < .02), less nasal secretions (P < .001), and less severe symptoms, including nasal congestion (P < .002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. Conclusion: In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.. desloratadine| antihistamine| nasal obstruction| seasonal allergic rhinitis| allergen exposure| rhinomanometry|mucosal blood-flow| receptor antagonists| atopic patients| efficacy| cetirizine| challenge| symptoms| safety| loratadine| management.	JUN-2002	desloratadine| antihistamine| nasal obstruction| seasonal allergic rhinitis| allergen exposure| rhinomanometry|mucosal blood-flow| receptor antagonists| atopic patients| efficacy| cetirizine| challenge| symptoms| safety| loratadine| management	Horak, F; Stubner, UP; Zieglmayer, R; Harris, AG	Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	desloratadine; antihistamine; nasal obstruction; seasonal allergic rhinitis; allergen exposure; rhinomanometry	MUCOSAL BLOOD-FLOW; RECEPTOR ANTAGONISTS; ATOPIC PATIENTS; EFFICACY; CETIRIZINE; CHALLENGE; SYMPTOMS; SAFETY; LORATADINE; MANAGEMENT	Background: Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). Objective: We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. Methods: In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. Results: Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P < .02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P less than or equal to .003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P < .02), less nasal secretions (P < .001), and less severe symptoms, including nasal congestion (P < .002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. Conclusion: In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.	24	78	2002	6	10.1067/mai.2002.124657	Allergy; Immunology
Violence: An unrecognized environmental exposure that may contribute to greater asthma morbidity in high risk inner-city populations. In the United States, rising trends in asthma prevalence and severity, which disproportionately impact minorities and the urban poor, have not been fully explained by traditional physical environmental risk factors. Exigencies of inner-city living can increase psychosocial risk factors (e.g., stress) that confer increased asthma morbidity. In the United States, chronic exposure to violence is a unique stressor existing in many high-risk urban neighborhoods. In this paper, we describe a series of cases that exemplify a temporal association between exposure to violence and the precipitation of asthma exacerbations in four urban pediatric patients. In the first three cases, the nature of the exposure is characterized by the proximity to violence, which ranged from direct victimization (through either the threat of physical assault or actual assault) to learning of the death of a peer. The fourth case characterizes a scenario in which a child was exposed to severe parental conflict (i.e., domestic violence) in the hospital setting. Increasingly, studies have begun to explore the effect of living in a violent environment, with a chronic pervasive atmosphere of fear and the perceived or real threat of violence, on health outcomes in population-based studies. Violence exposure may contribute to environmental demands that tax both the individual and the communities in which they live to impact the inner-city asthma burden. At the individual level, intervention strategies aimed to reduce violence exposure, to reduce stress, or to counsel victims or witnesses to violence may be complementary to more traditional asthma treatment in these populations. Change in policies that address the social, economic, and political factors that contribute to crime and violence in urban America may have broader impact.. asthma| case series| innercity| stress| violence|posttraumatic-stress-disorder| urban african-american| psychological stress| immune interactions| childhood asthma| life events| children| health| smoking| hospitalization.	OCT-2001	asthma| case series| innercity| stress| violence|posttraumatic-stress-disorder| urban african-american| psychological stress| immune interactions| childhood asthma| life events| children| health| smoking| hospitalization	Wright, RJ; Steinbach, SF	Violence: An unrecognized environmental exposure that may contribute to greater asthma morbidity in high risk inner-city populations		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; case series; innercity; stress; violence	POSTTRAUMATIC-STRESS-DISORDER; URBAN AFRICAN-AMERICAN; PSYCHOLOGICAL STRESS; IMMUNE INTERACTIONS; CHILDHOOD ASTHMA; LIFE EVENTS; CHILDREN; HEALTH; SMOKING; HOSPITALIZATION	In the United States, rising trends in asthma prevalence and severity, which disproportionately impact minorities and the urban poor, have not been fully explained by traditional physical environmental risk factors. Exigencies of inner-city living can increase psychosocial risk factors (e.g., stress) that confer increased asthma morbidity. In the United States, chronic exposure to violence is a unique stressor existing in many high-risk urban neighborhoods. In this paper, we describe a series of cases that exemplify a temporal association between exposure to violence and the precipitation of asthma exacerbations in four urban pediatric patients. In the first three cases, the nature of the exposure is characterized by the proximity to violence, which ranged from direct victimization (through either the threat of physical assault or actual assault) to learning of the death of a peer. The fourth case characterizes a scenario in which a child was exposed to severe parental conflict (i.e., domestic violence) in the hospital setting. Increasingly, studies have begun to explore the effect of living in a violent environment, with a chronic pervasive atmosphere of fear and the perceived or real threat of violence, on health outcomes in population-based studies. Violence exposure may contribute to environmental demands that tax both the individual and the communities in which they live to impact the inner-city asthma burden. At the individual level, intervention strategies aimed to reduce violence exposure, to reduce stress, or to counsel victims or witnesses to violence may be complementary to more traditional asthma treatment in these populations. Change in policies that address the social, economic, and political factors that contribute to crime and violence in urban America may have broader impact.	65	78	2001	5	10.2307/3454965	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
"Ole e 9, a major olive pollen allergen is a 1,3-beta-glucanase - Isolation, characterization, amino acid sequence, and tissue specificity. Olive pollen allergy is a clinical disorder affecting the human population of Mediterranean areas. A novel major allergen, Ole e 9, has been isolated from olive pollen by gel permeation, hydrophobic affinity, and reverse-phase high performance liquid chromatographies. It is involved in the allergic responses of 65% of patients suffering olive pollinosis. Ole e 9 (molecular mass of 46.4 kDa) displays 1,3-beta -endoglucanase activity (38.9 +/- 5.6 mg of glucose released/min x mu mol of protein at pH 4.5-6.0 using laminarin as substrate). It is the first 1,3-beta -glucanase, a member of the ""pathogenesis-related"" protein family, detected in pollen tissue. Seven tryptic peptides of the allergen were sequenced by Edman degradation and used for designing primers to clone the cDNA codifying the protein. Specific cDNA for Ole e 9 was synthesized from total RNA and amplified using the polymerase chain reaction. The allergen sequence showed an open reading frame of 460 amino acids comprising a putative signal peptide of 26 residues. It shows 39, 33, and 32% sequence identity including the catalytic residues when compared with 1,3-beta -glucanases from wheat, willow, and Arabidopsis thaliana, respectively. Northern blot analysis showed that Ole e 9 transcript is specifically expressed in the pollen tissue, and highly conserved counterparts were only detected in taxonomically related pollens.. pathogenesis-related proteins| dust-mite allergen| tree pollen| europea pollen| e-i| beta-1,3-glucanase| tobacco| expression| identification| purification."	JUL 27-2001	pathogenesis-related proteins| dust-mite allergen| tree pollen| europea pollen| e-i| beta-1,3-glucanase| tobacco| expression| identification| purification	Huecas, S; Villalba, M; Rodriguez, R	Ole e 9, a major olive pollen allergen is a 1,3-beta-glucanase - Isolation, characterization, amino acid sequence, and tissue specificity		JOURNAL OF BIOLOGICAL CHEMISTRY		PATHOGENESIS-RELATED PROTEINS; DUST-MITE ALLERGEN; TREE POLLEN; EUROPEA POLLEN; E-I; BETA-1,3-GLUCANASE; TOBACCO; EXPRESSION; IDENTIFICATION; PURIFICATION	"Olive pollen allergy is a clinical disorder affecting the human population of Mediterranean areas. A novel major allergen, Ole e 9, has been isolated from olive pollen by gel permeation, hydrophobic affinity, and reverse-phase high performance liquid chromatographies. It is involved in the allergic responses of 65% of patients suffering olive pollinosis. Ole e 9 (molecular mass of 46.4 kDa) displays 1,3-beta -endoglucanase activity (38.9 +/- 5.6 mg of glucose released/min x mu mol of protein at pH 4.5-6.0 using laminarin as substrate). It is the first 1,3-beta -glucanase, a member of the ""pathogenesis-related"" protein family, detected in pollen tissue. Seven tryptic peptides of the allergen were sequenced by Edman degradation and used for designing primers to clone the cDNA codifying the protein. Specific cDNA for Ole e 9 was synthesized from total RNA and amplified using the polymerase chain reaction. The allergen sequence showed an open reading frame of 460 amino acids comprising a putative signal peptide of 26 residues. It shows 39, 33, and 32% sequence identity including the catalytic residues when compared with 1,3-beta -glucanases from wheat, willow, and Arabidopsis thaliana, respectively. Northern blot analysis showed that Ole e 9 transcript is specifically expressed in the pollen tissue, and highly conserved counterparts were only detected in taxonomically related pollens."	68	78	2001	8	10.1074/jbc.M103041200	Biochemistry & Molecular Biology
Glutathione S-transferase genotypes and allergic responses to diisocyanate exposure. Diisocyanates are the most common low molecular weight chemicals to cause occupational asthma, However, only some 5-10% of exposed workers develop asthma, which suggests an underlying genetic susceptibility, Diisocyanates and their metabolites may be conjugated with glutathione by glutathione S-transferases (GSTs). We examined whether polymorphisms in the GSTM1, GSTM3, GSTP1 and GSTT1 genes modify allergic responses to diisocyanate exposure. The study population consisted of 182 diisocyanate exposed workers, 109 diagnosed with diisocyanate-induce asthma and 73 without asthma, Lack of the GSTM1 gene (null genotype) was associated with a 1.89-fold risk of diisocyanate-induced asthma [95% confidence interval (CI) 1.01-3.52]. Moreover, among the asthma patients, the GSTM1 null genotype was associated with lack of diisocyanate-specific immunoglobulin (Ig)E antibodies [odds ratio (OR) 0.18, 95% CI 0.05-0.61] and with late reaction in the specific bronchial provocation test (OR 2.82, 95% CI 1.15-6.88). Similarly, GSTM3 AA genotype was related to late reaction in the specific bronchial provocation test (OR 3.75, 95% CI 1.26-11.2), The GSTP1 Val/Val genotype, on the other hand, was related to high total IgE levels (OR 5.46, 95% CI 1.15-26.0). The most remarkable effect was seen for the combination of GSTM1 null anti. the GSTM3 AA genotype which was strongly associated with lack of diisocyanate-specific IgE antibodies (OR 0.09, 35% CI 0.01-0.73) and with late reaction in the bronchial provocation test (OR 11.0, 95% CI 2.19-55.3). The results suggest, for the first time, that the polymorphic GSTs, especially the mu class GSTs, play an important role in inception of ill effects related to occupational exposure to diisocyanates. Pharmacogenetics 11:437-445 (C) 2001 Lippincott Williams & Wilkins.. allergic responses| diisocyanates| individual susceptibility| gsts| occupational asthma| specific ige|occupational asthma| toluene-diisocyanate| methyl isocyanate| ige antibodies| polymorphism| association| susceptibility| workers| locus| alleles.	JUL-2001	allergic responses| diisocyanates| individual susceptibility| gsts| occupational asthma| specific ige|occupational asthma| toluene-diisocyanate| methyl isocyanate| ige antibodies| polymorphism| association| susceptibility| workers| locus| alleles	Piirila, P; Wikman, H; Luukkonen, R; Kaaria, K; Rosenberg, C; Nordman, H; Norppa, H; Vainio, H; Hirvonen, A	Glutathione S-transferase genotypes and allergic responses to diisocyanate exposure		PHARMACOGENETICS	allergic responses; diisocyanates; individual susceptibility; GSTs; occupational asthma; specific IgE	OCCUPATIONAL ASTHMA; TOLUENE-DIISOCYANATE; METHYL ISOCYANATE; IGE ANTIBODIES; POLYMORPHISM; ASSOCIATION; SUSCEPTIBILITY; WORKERS; LOCUS; ALLELES	Diisocyanates are the most common low molecular weight chemicals to cause occupational asthma, However, only some 5-10% of exposed workers develop asthma, which suggests an underlying genetic susceptibility, Diisocyanates and their metabolites may be conjugated with glutathione by glutathione S-transferases (GSTs). We examined whether polymorphisms in the GSTM1, GSTM3, GSTP1 and GSTT1 genes modify allergic responses to diisocyanate exposure. The study population consisted of 182 diisocyanate exposed workers, 109 diagnosed with diisocyanate-induce asthma and 73 without asthma, Lack of the GSTM1 gene (null genotype) was associated with a 1.89-fold risk of diisocyanate-induced asthma [95% confidence interval (CI) 1.01-3.52]. Moreover, among the asthma patients, the GSTM1 null genotype was associated with lack of diisocyanate-specific immunoglobulin (Ig)E antibodies [odds ratio (OR) 0.18, 95% CI 0.05-0.61] and with late reaction in the specific bronchial provocation test (OR 2.82, 95% CI 1.15-6.88). Similarly, GSTM3 AA genotype was related to late reaction in the specific bronchial provocation test (OR 3.75, 95% CI 1.26-11.2), The GSTP1 Val/Val genotype, on the other hand, was related to high total IgE levels (OR 5.46, 95% CI 1.15-26.0). The most remarkable effect was seen for the combination of GSTM1 null anti. the GSTM3 AA genotype which was strongly associated with lack of diisocyanate-specific IgE antibodies (OR 0.09, 35% CI 0.01-0.73) and with late reaction in the bronchial provocation test (OR 11.0, 95% CI 2.19-55.3). The results suggest, for the first time, that the polymorphic GSTs, especially the mu class GSTs, play an important role in inception of ill effects related to occupational exposure to diisocyanates. Pharmacogenetics 11:437-445 (C) 2001 Lippincott Williams & Wilkins.	35	78	2001	9	10.1097/00008571-200107000-00007	Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy
The role and abatement of fungal allergens in allergic diseases. Sensitivity to a variety of fungi is known to be a factor in allergic rhinitis and asthma. In this review methods for measuring exposure to fungi in the indoor environment are evaluated. A variety of markers for the presence of fungi are also described in addition to their known relationship to either toxic or adverse immunologic effects. Key studies documenting the clinical effects of different types of fungi are also reviewed, as well as a description of abatement methods that either have been successful or need further investigation. Although many studies have shown an association between exposure to fungi and allergic disease, in many cases a direct cause-and-effect relationship has not been established. Improved knowledge of the epidemiology and mechanisms behind fungal-induced human disease will hopefully establish this causal link and suggest methods for reducing morbidity.. fungi| allergic disease| asthma| environment| exposure| abatement|nutrition examination survey| major alternaria allergen| sick building syndrome| 2nd national-health| school-age-children| dust mite| indoor air| residential characteristics| environmental-factors| respiratory symptoms.	MAR-2001	fungi| allergic disease| asthma| environment| exposure| abatement|nutrition examination survey| major alternaria allergen| sick building syndrome| 2nd national-health| school-age-children| dust mite| indoor air| residential characteristics| environmental-factors| respiratory symptoms	Bush, RK; Portnoy, JM	The role and abatement of fungal allergens in allergic diseases		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	fungi; allergic disease; asthma; environment; exposure; abatement	NUTRITION EXAMINATION SURVEY; MAJOR ALTERNARIA ALLERGEN; SICK BUILDING SYNDROME; 2ND NATIONAL-HEALTH; SCHOOL-AGE-CHILDREN; DUST MITE; INDOOR AIR; RESIDENTIAL CHARACTERISTICS; ENVIRONMENTAL-FACTORS; RESPIRATORY SYMPTOMS	Sensitivity to a variety of fungi is known to be a factor in allergic rhinitis and asthma. In this review methods for measuring exposure to fungi in the indoor environment are evaluated. A variety of markers for the presence of fungi are also described in addition to their known relationship to either toxic or adverse immunologic effects. Key studies documenting the clinical effects of different types of fungi are also reviewed, as well as a description of abatement methods that either have been successful or need further investigation. Although many studies have shown an association between exposure to fungi and allergic disease, in many cases a direct cause-and-effect relationship has not been established. Improved knowledge of the epidemiology and mechanisms behind fungal-induced human disease will hopefully establish this causal link and suggest methods for reducing morbidity.	94	78	2001	11		Allergy; Immunology
Benefits of high altitude allergen avoidance in atopic adolescents with moderate to severe asthma, over and above treatment with high dose inhaled steroids. Background Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure. Objective We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS. Methods Eighteen atopic asthmatic adolescents (12-18 yr, 500-2000 mug ICS daily) with established house dust mite allergy, participated in a parallel-group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10-week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups. Results During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U-EPX), leukotriene E-4 (U-LTE4) and 9 alpha 11 beta prostaglandin F-2 (U-9 alpha 11 beta PGF(2)) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U-EPX (P < 0.05) and U-LTE4 (P < 0.05) were maintained. Conclusion A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long-acting beta (2)-agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short-term, rigorous allergen avoidance can improve the long-term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.. allergen avoidance| house dust mite| severe asthma| induced sputum| high altitude| urine| epx| lte4| 9 alpha 11 beta-pgf(2)|bronchial hyperresponsiveness| clinical severity| dust mites| children| inflammation| glucocorticoids| management| excretion| protein.	MAR-2001	allergen avoidance| house dust mite| severe asthma| induced sputum| high altitude| urine| epx| lte4| 9 alpha 11 beta-pgf(2)|bronchial hyperresponsiveness| clinical severity| dust mites| children| inflammation| glucocorticoids| management| excretion| protein	Grootendorst, DC; Dahlen, SE; Van den Bos, JW; Duiverman, EJ; Veselic-Charvat, M; Vrijlandt, EJLE; O'Sullivan, S; Kumlin, M; Sterk, PJ; Roldaan, AC	Benefits of high altitude allergen avoidance in atopic adolescents with moderate to severe asthma, over and above treatment with high dose inhaled steroids		CLINICAL AND EXPERIMENTAL ALLERGY	allergen avoidance; house dust mite; severe asthma; induced sputum; high altitude; urine; EPX; LTE4; 9 alpha 11 beta-PGF(2)	BRONCHIAL HYPERRESPONSIVENESS; CLINICAL SEVERITY; DUST MITES; CHILDREN; INFLAMMATION; GLUCOCORTICOIDS; MANAGEMENT; EXCRETION; PROTEIN	Background Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure. Objective We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS. Methods Eighteen atopic asthmatic adolescents (12-18 yr, 500-2000 mug ICS daily) with established house dust mite allergy, participated in a parallel-group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10-week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups. Results During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U-EPX), leukotriene E-4 (U-LTE4) and 9 alpha 11 beta prostaglandin F-2 (U-9 alpha 11 beta PGF(2)) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U-EPX (P < 0.05) and U-LTE4 (P < 0.05) were maintained. Conclusion A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long-acting beta (2)-agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short-term, rigorous allergen avoidance can improve the long-term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.	32	78	2001	9	10.1046/j.1365-2222.2001.01022.x	Allergy; Immunology
Consistency of care with national guidelines for children with asthma in managed care. Objective: To evaluate the consistency of pediatric asthma care with the National Asthma Education and Prevention Program Guidelines. Design: Cross-sectional survey at 2 managed care organizations in the United States (winter 1997-1998). The participants were parents of children (n = 318) age 5 to 17 years with asthma. There were no interventions. The outcome measures were indicators of care in 4 domains: (1) periodic physiologic assessment, (2) proper use of medications, (3) patient education, and (4) control of factors contributing to asthma severity. Results: Of 533 eligible patients with asthma, 318 (60%) parents responded; 59% of children were male, 76% were white, and 60% were aged 5 to 10 years. Deficiencies in care were identified in all care domains including, for patients with moderate and severe persistent symptoms, only 55% used long-term control medication daily, 49% had written instructions for handling asthma attacks, 44% had instructions for adjustment of medication before exposures, 56% had undergone allergy testing, and 54% had undergone pulmonary function testing. Conclusions: There are significant opportunities to improve the quality of care for children with asthma enrolled in managed care. A comprehensive approach to improving care may be necessary to address multiple aspects of care where opportunities exist.. beta-agonists| quality| therapy.	JAN-2001	beta-agonists| quality| therapy	Diette, GB; Skinner, EA; Markson, LE; Algatt-Bergstrom, P; Nguyen, TTH; Clark, RD; Wu, AW	Consistency of care with national guidelines for children with asthma in managed care		JOURNAL OF PEDIATRICS		BETA-AGONISTS; QUALITY; THERAPY	Objective: To evaluate the consistency of pediatric asthma care with the National Asthma Education and Prevention Program Guidelines. Design: Cross-sectional survey at 2 managed care organizations in the United States (winter 1997-1998). The participants were parents of children (n = 318) age 5 to 17 years with asthma. There were no interventions. The outcome measures were indicators of care in 4 domains: (1) periodic physiologic assessment, (2) proper use of medications, (3) patient education, and (4) control of factors contributing to asthma severity. Results: Of 533 eligible patients with asthma, 318 (60%) parents responded; 59% of children were male, 76% were white, and 60% were aged 5 to 10 years. Deficiencies in care were identified in all care domains including, for patients with moderate and severe persistent symptoms, only 55% used long-term control medication daily, 49% had written instructions for handling asthma attacks, 44% had instructions for adjustment of medication before exposures, 56% had undergone allergy testing, and 54% had undergone pulmonary function testing. Conclusions: There are significant opportunities to improve the quality of care for children with asthma enrolled in managed care. A comprehensive approach to improving care may be necessary to address multiple aspects of care where opportunities exist.	20	78	2001	6	10.1067/mpd.2001.109600	Pediatrics
Chronic rhinosinusitis: Allergy and sinus computed tomography relationships. The management of chronic or recurrent rhinosinusitis problems is multifaceted and should include consideration of contributory and potentially correctable medical and anatomic factors. To date, the relationship between allergy and rhinosinusitis has not been clearly defined. The purpose of this study is to improve understanding of the relative roles of perennial and seasonal allergens in the cause of chronic rhinosinusitis. A retrospective review of 200 consecutive patients was carried out on patients who had chronic rhinosinusitis refractory to medical therapy and who subsequently underwent functional endoscopic sinus surgery. All of these patients had allergy testing for common perennial and seasonal inhalant allergens before surgery. Each patient had sinus CT imaging before undergoing the surgery. The CT scans of each patient were staged according to a validated, standardized grading system by investigators blinded to allergic profile. Allergy testing indicated that 84% of all patients tested positive for allergies. Moreover, 60% of all patients had significant allergic sensitivity; 52% of all patients had multiple allergen sensitivities. Furthermore, there was a predominance of perennial allergens, especially house dust mite over seasonal allergens. The vast majority of our patients undergoing functional endoscopic sinus surgery had concomitant allergy. This study highlights the potential contribution of perennial allergies to the development of rhinosinusitis, Given this direction, future studies may reveal that in the care of patients with perennial allergic rhinitis, early intervention with identification of the offending allergen(s), and subsequent treatment through avoidance, pharmacotherapy, and/or immunotherapy may help in the prevention of recurrent and chronic rhinosinusitis.. management.	DEC-2000	management	Emanuel, IA; Shah, SB	Chronic rhinosinusitis: Allergy and sinus computed tomography relationships		OTOLARYNGOLOGY-HEAD AND NECK SURGERY		MANAGEMENT	The management of chronic or recurrent rhinosinusitis problems is multifaceted and should include consideration of contributory and potentially correctable medical and anatomic factors. To date, the relationship between allergy and rhinosinusitis has not been clearly defined. The purpose of this study is to improve understanding of the relative roles of perennial and seasonal allergens in the cause of chronic rhinosinusitis. A retrospective review of 200 consecutive patients was carried out on patients who had chronic rhinosinusitis refractory to medical therapy and who subsequently underwent functional endoscopic sinus surgery. All of these patients had allergy testing for common perennial and seasonal inhalant allergens before surgery. Each patient had sinus CT imaging before undergoing the surgery. The CT scans of each patient were staged according to a validated, standardized grading system by investigators blinded to allergic profile. Allergy testing indicated that 84% of all patients tested positive for allergies. Moreover, 60% of all patients had significant allergic sensitivity; 52% of all patients had multiple allergen sensitivities. Furthermore, there was a predominance of perennial allergens, especially house dust mite over seasonal allergens. The vast majority of our patients undergoing functional endoscopic sinus surgery had concomitant allergy. This study highlights the potential contribution of perennial allergies to the development of rhinosinusitis, Given this direction, future studies may reveal that in the care of patients with perennial allergic rhinitis, early intervention with identification of the offending allergen(s), and subsequent treatment through avoidance, pharmacotherapy, and/or immunotherapy may help in the prevention of recurrent and chronic rhinosinusitis.	6	78	2000	5	10.1067/mhn.2000.110961	Otorhinolaryngology; Surgery
Eosinophilopoiesis in a murine model of allergic airway eosinophilia: Involvement of bone marrow IL-5 and IL-5 receptor alpha. The airway inflammation in asthma is dominated by eosinophils. The aim of this study was to elucidate the contribution of newly produced eosinophils in airway allergic inflammation and to determine mechanisms of any enhanced eosinophilopoiesis, OVA-sensitized BALB/c mice were repeatedly exposed to allergen via airway route. Newly produced cells were identified using a thymidine analog, 5-bromo-2'-deoxyuridine, which is incorporated into DNA during mitosis. Identification of IL-5-producing cells in the bone marrow was performed using FAGS. Bone marrow CD3(+) cells were enriched to evaluate IL-5-protein release in vitro. Anti-ILS-treatment (TRFK-5) was given either systemically or directly to the airways. IL-SR-bearing cells were localized by immunocytochemistry. Repeated airway allergen exposure caused prominent airway eosinophilia after three to five exposures, and increased the number of immature eosinophils in the bone marrow. Up to 78% of bronchoalveolar lavage (BAL) granulocytes were 5-bromo-2'-deoxyuridine positive. After three allergen exposures, both CD3+ and non-CD3 cells acquired from the bone marrow expressed and released IL-5-protein. Anti-IL-5 given i.p. inhibited both bone marrow and airway eosinophilia. Intranasal administration of anti-IL-5 also reduced BAL eosinophilia, partly via local effects in the airways. Bone marrow cells, but not BAL eosinophils, displayed stainable amounts of the IL-5R alpha-chain. We conclude that the bone marrow is activated by airway allergen exposure, and that newly produced eosinophils contribute to a substantial degree to the airway eosinophilia induced by allergen. Airway allergen exposure increases the number of cells expressing IL-5-protein in the bone marrow. The bone marrow, as well as the lung, are possible targets for anti-IL-5-treatment.. messenger-rna| in-vivo| interleukin-5 expression| circulating eosinophils| pulmonary inflammation| bronchial biopsies| mild asthma| lung damage| mast-cells| t-cells.	OCT 1-2000	messenger-rna| in-vivo| interleukin-5 expression| circulating eosinophils| pulmonary inflammation| bronchial biopsies| mild asthma| lung damage| mast-cells| t-cells	Tomaki, M; Zhao, LL; Lundahl, J; Sjostrand, M; Jordana, M; Linden, A; O'Byrne, P; Lotvall, J	Eosinophilopoiesis in a murine model of allergic airway eosinophilia: Involvement of bone marrow IL-5 and IL-5 receptor alpha		JOURNAL OF IMMUNOLOGY		MESSENGER-RNA; IN-VIVO; INTERLEUKIN-5 EXPRESSION; CIRCULATING EOSINOPHILS; PULMONARY INFLAMMATION; BRONCHIAL BIOPSIES; MILD ASTHMA; LUNG DAMAGE; MAST-CELLS; T-CELLS	The airway inflammation in asthma is dominated by eosinophils. The aim of this study was to elucidate the contribution of newly produced eosinophils in airway allergic inflammation and to determine mechanisms of any enhanced eosinophilopoiesis, OVA-sensitized BALB/c mice were repeatedly exposed to allergen via airway route. Newly produced cells were identified using a thymidine analog, 5-bromo-2'-deoxyuridine, which is incorporated into DNA during mitosis. Identification of IL-5-producing cells in the bone marrow was performed using FAGS. Bone marrow CD3(+) cells were enriched to evaluate IL-5-protein release in vitro. Anti-ILS-treatment (TRFK-5) was given either systemically or directly to the airways. IL-SR-bearing cells were localized by immunocytochemistry. Repeated airway allergen exposure caused prominent airway eosinophilia after three to five exposures, and increased the number of immature eosinophils in the bone marrow. Up to 78% of bronchoalveolar lavage (BAL) granulocytes were 5-bromo-2'-deoxyuridine positive. After three allergen exposures, both CD3+ and non-CD3 cells acquired from the bone marrow expressed and released IL-5-protein. Anti-IL-5 given i.p. inhibited both bone marrow and airway eosinophilia. Intranasal administration of anti-IL-5 also reduced BAL eosinophilia, partly via local effects in the airways. Bone marrow cells, but not BAL eosinophils, displayed stainable amounts of the IL-5R alpha-chain. We conclude that the bone marrow is activated by airway allergen exposure, and that newly produced eosinophils contribute to a substantial degree to the airway eosinophilia induced by allergen. Airway allergen exposure increases the number of cells expressing IL-5-protein in the bone marrow. The bone marrow, as well as the lung, are possible targets for anti-IL-5-treatment.	57	78	2000	11		Immunology
Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis. Background Smoke-free legislation has the potential to reduce the substantive disease burden associated with second-hand smoke exposure, particularly in children. We investigated the effect of smoke-free legislation on perinatal and child health. Methods We searched 14 online databases from January, 1975 to May, 2013, with no language restrictions, for published studies, and the WHO International Clinical Trials Registry Platform for unpublished studies. Citations and reference lists of articles of interest were screened and an international expert panel was contacted to identify additional studies. We included studies undertaken with designs approved by the Cochrane Effective Practice and Organisation of Care that reported associations between smoking bans in workplaces, public places, or both, and one or more predefined early-life health indicator. The primary outcomes were preterm birth, low birthweight, and hospital attendances for asthma. Effect estimates were pooled with random-effects meta-analysis. This study is registered with PROSPERO, number CRD42013003522. Findings We identified 11 eligible studies (published 2008-13), involving more than 2.5 million births and 247 168 asthma exacerbations. All studies used interrupted time-series designs. Five North American studies described local bans and six European studies described national bans. Risk of bias was high for one study, moderate for six studies, and low for four studies. Smoke-free legislation was associated with reductions in preterm birth (four studies, 1 366 862 individuals; -10.4% [95% CI -18.8 to -2.0]; p=0.016) and hospital attendances for asthma (three studies, 225 753 events: -10.1% [95% CI -15.2 to -5.0]; p=0.0001). No significant effect on low birthweight was identified (six studies, >1.9 million individuals: -1.7% [95% CI -5.1 to 1.6]; p=0.31). Interpretation Smoke-free legislation is associated with substantial reductions in preterm births and hospital attendance for asthma. Together with the health benefits in adults, this study provides strong support for WHO recommendations to create smoke-free environments.. environmental tobacco-smoke| preterm births analysis| free air laws| secondhand smoke| noncommunicable diseases| maternal smoking| nonsmoking youth| public places| global burden| exposure.	MAY 3-2014	environmental tobacco-smoke| preterm births analysis| free air laws| secondhand smoke| noncommunicable diseases| maternal smoking| nonsmoking youth| public places| global burden| exposure	Been, JV; Nurmatov, UB; Cox, B; Nawrot, TS; van Schayck, CP; Sheikh, A	Effect of smoke-free legislation on perinatal and child health: a systematic review and meta-analysis		LANCET		ENVIRONMENTAL TOBACCO-SMOKE; PRETERM BIRTHS ANALYSIS; FREE AIR LAWS; SECONDHAND SMOKE; NONCOMMUNICABLE DISEASES; MATERNAL SMOKING; NONSMOKING YOUTH; PUBLIC PLACES; GLOBAL BURDEN; EXPOSURE	Background Smoke-free legislation has the potential to reduce the substantive disease burden associated with second-hand smoke exposure, particularly in children. We investigated the effect of smoke-free legislation on perinatal and child health. Methods We searched 14 online databases from January, 1975 to May, 2013, with no language restrictions, for published studies, and the WHO International Clinical Trials Registry Platform for unpublished studies. Citations and reference lists of articles of interest were screened and an international expert panel was contacted to identify additional studies. We included studies undertaken with designs approved by the Cochrane Effective Practice and Organisation of Care that reported associations between smoking bans in workplaces, public places, or both, and one or more predefined early-life health indicator. The primary outcomes were preterm birth, low birthweight, and hospital attendances for asthma. Effect estimates were pooled with random-effects meta-analysis. This study is registered with PROSPERO, number CRD42013003522. Findings We identified 11 eligible studies (published 2008-13), involving more than 2.5 million births and 247 168 asthma exacerbations. All studies used interrupted time-series designs. Five North American studies described local bans and six European studies described national bans. Risk of bias was high for one study, moderate for six studies, and low for four studies. Smoke-free legislation was associated with reductions in preterm birth (four studies, 1 366 862 individuals; -10.4% [95% CI -18.8 to -2.0]; p=0.016) and hospital attendances for asthma (three studies, 225 753 events: -10.1% [95% CI -15.2 to -5.0]; p=0.0001). No significant effect on low birthweight was identified (six studies, >1.9 million individuals: -1.7% [95% CI -5.1 to 1.6]; p=0.31). Interpretation Smoke-free legislation is associated with substantial reductions in preterm births and hospital attendance for asthma. Together with the health benefits in adults, this study provides strong support for WHO recommendations to create smoke-free environments.	76	77	2014	12	10.1016/S0140-6736(14)60082-9	General & Internal Medicine
Early regular egg exposure in infants with eczema: A randomized controlled trial. Background: Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy. Objective: We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema. Methods: In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests. Results: A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had eggspecific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P 5.11). Egg-specific IgG4 levels were significantly (P <.001) greater in the egg group at both 8 and 12 months. Conclusion: Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age.. allergy prevention| complementary feeding| eczema| egg| food allergy| oral tolerance| randomized controlled trial|oral immunotherapy| allergic diseases| atopic-dermatitis| birth cohort| children| fish| sensitization| challenge| tolerance| formulas.	AUG-2013	allergy prevention| complementary feeding| eczema| egg| food allergy| oral tolerance| randomized controlled trial|oral immunotherapy| allergic diseases| atopic-dermatitis| birth cohort| children| fish| sensitization| challenge| tolerance| formulas	Palmer, DJ; Metcalfe, J; Makrides, M; Gold, MS; Quinn, P; West, CE; Loh, R; Prescott, SL	Early regular egg exposure in infants with eczema: A randomized controlled trial		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergy prevention; complementary feeding; eczema; egg; food allergy; oral tolerance; randomized controlled trial	ORAL IMMUNOTHERAPY; ALLERGIC DISEASES; ATOPIC-DERMATITIS; BIRTH COHORT; CHILDREN; FISH; SENSITIZATION; CHALLENGE; TOLERANCE; FORMULAS	Background: Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy. Objective: We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema. Methods: In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests. Results: A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had eggspecific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P 5.11). Egg-specific IgG4 levels were significantly (P <.001) greater in the egg group at both 8 and 12 months. Conclusion: Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age.	25	77	2013	7	10.1016/j.jaci.2013.05.002	Allergy; Immunology
Food protein functionality: A comprehensive approach. Food protein functionality has classically been viewed from the perspective of how single molecules or protein ingredients function in solutions and form simple colloidal structures. Based on this approach, tests on protein solutions are used to produce values for solubility, thermal stability, gelation, emulsifying, foaming, fat binding and water binding to name a few. While this approach is beneficial in understanding the properties of specific proteins and ingredients, it is somewhat restricted in predicting performance in real foods where the complexities of ingredients and processing operations have a significant affect on the colloidal structures and therefore overall properties of the final food product. In addition, focusing on proteins as just biopolymers used to create food structures ignores the biological functions of proteins in the diet. These can be beneficial, as in providing amino acids for protein synthesis or bioactive peptides, or these can be detrimental, as in causing a food allergic response. This review will focus on integrating the colloidal/polymer and biological aspects of protein functionality. This will be done using foams and gels to illustrate colloidal/polymer aspects and bioactive peptides and allergenicity to demonstrate biological function. (C) 2011 Elsevier Ltd. All rights reserved.. protein| protein functionality| foams| gels| emulsions| bioactivity| allergenicity|egg-white protein| bovine beta-lactoglobulin| peanut arachis-hypogaea| ige-binding epitopes| air-water-interface| cows milk allergy| cold-set gels| whey-protein| alpha-lactalbumin| bioactive peptides.	NEW YORK-650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA	protein| protein functionality| foams| gels| emulsions| bioactivity| allergenicity|egg-white protein| bovine beta-lactoglobulin| peanut arachis-hypogaea| ige-binding epitopes| air-water-interface| cows milk allergy| cold-set gels| whey-protein| alpha-lactalbumin| bioactive peptides	Foegeding, EA; Davis, JP	Food protein functionality: A comprehensive approach		FOOD HYDROCOLLOIDS	Protein; Protein functionality; Foams; Gels; Emulsions; Bioactivity; Allergenicity	EGG-WHITE PROTEIN; BOVINE BETA-LACTOGLOBULIN; PEANUT ARACHIS-HYPOGAEA; IGE-BINDING EPITOPES; AIR-WATER-INTERFACE; COWS MILK ALLERGY; COLD-SET GELS; WHEY-PROTEIN; ALPHA-LACTALBUMIN; BIOACTIVE PEPTIDES	Food protein functionality has classically been viewed from the perspective of how single molecules or protein ingredients function in solutions and form simple colloidal structures. Based on this approach, tests on protein solutions are used to produce values for solubility, thermal stability, gelation, emulsifying, foaming, fat binding and water binding to name a few. While this approach is beneficial in understanding the properties of specific proteins and ingredients, it is somewhat restricted in predicting performance in real foods where the complexities of ingredients and processing operations have a significant affect on the colloidal structures and therefore overall properties of the final food product. In addition, focusing on proteins as just biopolymers used to create food structures ignores the biological functions of proteins in the diet. These can be beneficial, as in providing amino acids for protein synthesis or bioactive peptides, or these can be detrimental, as in causing a food allergic response. This review will focus on integrating the colloidal/polymer and biological aspects of protein functionality. This will be done using foams and gels to illustrate colloidal/polymer aspects and bioactive peptides and allergenicity to demonstrate biological function. (C) 2011 Elsevier Ltd. All rights reserved.	Halbert, RJ (reprint author), Cerner Hlth Insights, 9100 Wilshire Blvd,Suite 655E, Beverly Hills, CA 90212 USA.	rhalbert@cerner.com	650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA			1364
Efficacy of a management plan based on severity assessment in longitudinal and case-controlled studies of 747 children with nut allergy: proposal for good practice. There are few data on the long-term management of children with peanut/nut allergy. Advice is variable and often inadequate; further reactions are common. There is no consensus on the criteria for prescription of rescue medication, particularly adrenaline. A longitudinal prospective and case-control study in a tertiary allergy clinic. Patients/parents/school staff of 747 children with confirmed peanut or tree nut allergy received detailed verbal and written advice on nut avoidance, training in recognition and (self-) treatment of reactions and a written treatment plan. The severity of nut allergy was graded (mild-severe) and emergency medication was allocated according to our criteria: all received oral antihistamines, injected adrenaline (EpiPen) was given to those with reactions with airway narrowing, milder reactions to low-dose exposure or concomitant asthma. At annual follow-up over 25 906 patient-months (median: 39 months) retraining was given and details of further reactions (frequency, severity and treatment) were obtained. Criteria for allocation of EpiPen were evaluated. The worst reaction pre-enrolment was mild in 64% and moderate/severe in 36% (airway narrowing). Of 615 subjects followed up, 21% had a further reaction (eightfold reduction in frequency), mostly mild. There was a 60-fold reduction in the frequency of severe reactions. Of those with a moderate-severe initial reaction, 99.5% had no or a less severe follow-up reaction. No child with a mild or severe index reaction had a severe follow-up reaction. Only 1/615 (0.2%) had a severe follow-up reaction and only 2/615 (0.3%) used adrenaline, both successfully and had it available according to our criteria. Of mild-moderate reactions, 77% required oral antihistamines alone and 15% no treatment. Children who had follow-up reactions had more frequent and severe reactions pre-enrolment. The management plan greatly reduced the frequency and severity of further reactions and was successful for all children. Our criteria for selective prescription of EpiPen in the context of this management plan were appropriate. This is the first study to provide evidence on which to inform practice.. food| nut| allergy| management plan| anaphylaxis|peanut allergy| anaphylactic reactions| food challenges| prevalence| features| schools.	JUN-2005	food| nut| allergy| management plan| anaphylaxis|peanut allergy| anaphylactic reactions| food challenges| prevalence| features| schools	Ewan, PW; Clark, AT	Efficacy of a management plan based on severity assessment in longitudinal and case-controlled studies of 747 children with nut allergy: proposal for good practice		CLINICAL AND EXPERIMENTAL ALLERGY	food; nut; allergy; Management plan; anaphylaxis	PEANUT ALLERGY; ANAPHYLACTIC REACTIONS; FOOD CHALLENGES; PREVALENCE; FEATURES; SCHOOLS	There are few data on the long-term management of children with peanut/nut allergy. Advice is variable and often inadequate; further reactions are common. There is no consensus on the criteria for prescription of rescue medication, particularly adrenaline. A longitudinal prospective and case-control study in a tertiary allergy clinic. Patients/parents/school staff of 747 children with confirmed peanut or tree nut allergy received detailed verbal and written advice on nut avoidance, training in recognition and (self-) treatment of reactions and a written treatment plan. The severity of nut allergy was graded (mild-severe) and emergency medication was allocated according to our criteria: all received oral antihistamines, injected adrenaline (EpiPen) was given to those with reactions with airway narrowing, milder reactions to low-dose exposure or concomitant asthma. At annual follow-up over 25 906 patient-months (median: 39 months) retraining was given and details of further reactions (frequency, severity and treatment) were obtained. Criteria for allocation of EpiPen were evaluated. The worst reaction pre-enrolment was mild in 64% and moderate/severe in 36% (airway narrowing). Of 615 subjects followed up, 21% had a further reaction (eightfold reduction in frequency), mostly mild. There was a 60-fold reduction in the frequency of severe reactions. Of those with a moderate-severe initial reaction, 99.5% had no or a less severe follow-up reaction. No child with a mild or severe index reaction had a severe follow-up reaction. Only 1/615 (0.2%) had a severe follow-up reaction and only 2/615 (0.3%) used adrenaline, both successfully and had it available according to our criteria. Of mild-moderate reactions, 77% required oral antihistamines alone and 15% no treatment. Children who had follow-up reactions had more frequent and severe reactions pre-enrolment. The management plan greatly reduced the frequency and severity of further reactions and was successful for all children. Our criteria for selective prescription of EpiPen in the context of this management plan were appropriate. This is the first study to provide evidence on which to inform practice.	20	77	2005	6	10.1111/j.1365-2222.2005.02266.x	Allergy; Immunology
Antigen-specific CD4(+) T cells drive airway in smooth muscle remodeling experimental asthma. Airway smooth muscle (ASM) growth contributes to the mechanism of airway hyperresponsiveness in asthma. Here we demonstrate that CD4(+) T cells, central to chronic airway inflammation, drive ASM remodeling in experimental asthma. Adoptive transfer of CD4(+) T cells from sensitized rats induced an increase in proliferation and inhibition of apoptosis of airway myocytes in naive recipients upon repeated antigen challenge, which resulted in an increase in ASM mass. Genetically modified CD4(+) T cells expressing enhanced GFP (EGFP) were localized by confocal microscopy in juxtaposition to ASM cells, which suggests that CD4(+) T cells may modulate ASM cell function through direct cell-cell interaction in vivo. Coculture of antigen-stimulated CD4(+) T cells with cell cycle-arrested ASM cells induced myocyte proliferation, dependent on T cell activation and direct T cell-myocyte contact. Reciprocally, direct cell contact prevented postactivation T cell apoptosis, which suggests receptor-mediated T cell-myocyte crosstalk. Overall, our data demonstrate that activated CD4(+) T cells drive ASM remodeling in experimental asthma and suggest that a direct cell-cell interaction participates in CD4(+) T cell regulation of myocyte turnover and induction of remodeling.. brown-norway rats| repeated allergen exposure| dna-synthesis| in-vivo| expression| inflammation| lymphocytes| fas| hyperresponsiveness| transduction.	JUN-2005	brown-norway rats| repeated allergen exposure| dna-synthesis| in-vivo| expression| inflammation| lymphocytes| fas| hyperresponsiveness| transduction	Ramos-Barbon, D; Presley, JF; Hamid, QA; Fixman, ED; Martin, JG	Antigen-specific CD4(+) T cells drive airway in smooth muscle remodeling experimental asthma		JOURNAL OF CLINICAL INVESTIGATION		BROWN-NORWAY RATS; REPEATED ALLERGEN EXPOSURE; DNA-SYNTHESIS; IN-VIVO; EXPRESSION; INFLAMMATION; LYMPHOCYTES; FAS; HYPERRESPONSIVENESS; TRANSDUCTION	Airway smooth muscle (ASM) growth contributes to the mechanism of airway hyperresponsiveness in asthma. Here we demonstrate that CD4(+) T cells, central to chronic airway inflammation, drive ASM remodeling in experimental asthma. Adoptive transfer of CD4(+) T cells from sensitized rats induced an increase in proliferation and inhibition of apoptosis of airway myocytes in naive recipients upon repeated antigen challenge, which resulted in an increase in ASM mass. Genetically modified CD4(+) T cells expressing enhanced GFP (EGFP) were localized by confocal microscopy in juxtaposition to ASM cells, which suggests that CD4(+) T cells may modulate ASM cell function through direct cell-cell interaction in vivo. Coculture of antigen-stimulated CD4(+) T cells with cell cycle-arrested ASM cells induced myocyte proliferation, dependent on T cell activation and direct T cell-myocyte contact. Reciprocally, direct cell contact prevented postactivation T cell apoptosis, which suggests receptor-mediated T cell-myocyte crosstalk. Overall, our data demonstrate that activated CD4(+) T cells drive ASM remodeling in experimental asthma and suggest that a direct cell-cell interaction participates in CD4(+) T cell regulation of myocyte turnover and induction of remodeling.	36	77	2005	10	10.1172/JCI19711	Research & Experimental Medicine
Innate defence functions of macrophages can be biased by nano-sized ceramic and metallic particles. Nano-sized particles of ceramic and metallic materials are generated by high-tech industrial activities, and can be generated from worn-out replacement and prosthetic implants. The interaction with the human body of such nanoparticles has been investigated, with a particular emphasis on innate defence mechanisms. Human macrophages (PMA-differentiated myelomonocytic U-937 cells) were exposed in vitro to non-toxic concentrations of TiO2 SiO2 ZrO2 or Co nanoparticles, and their inflammatory response (expression of TLR receptors and co-receptors, and cytokine production) was examined. Expression of TLR receptors was generally unaffected by exposure to the different nanoparticles, except for some notable cases. Exposure to nanoparticles of ZrO2 (and to a lesser extent TiO2), upregulated expression of viral TLR receptors TLR3 and TLR7. Expression of TLR10 was also increased by TiO2 and ZrO2 nanoparticles. On the other hand, TLR9 expression was decreased by SiO2 nanoparticles, and expression of the co-receptor CD14 was inhibited by Co nanoparticles. Basal and LPS-induced production of cytokines 1L-1beta, TNF-alpha, and 1L-1Ra was examined in macrophages exposed to nanoparticles. SiO2 nanoparticles strongly biased naive macrophages towards inflammation (M1 polarisation), by selectively inducing production of inflammatory cytokines IL-1beta and TNF-alpha. SiO2 nanoparticles also significantly amplified the inflammatory phenotype of LPS-polarised M1 macrophages. Other ceramic nanoparticles had little influence on cytokine production, either in resting macrophages, or in LPS-activated cells. Generally, Co nanoparticles had an overall pro-inflammatory effect on naive macrophages, by reducing anti-inflammatory IL-1Ra and inducing inflammatory TNF-alpha. However, Co nanoparticles reduced production of IL-1beta and IL-1Ra, but not TNF-alpha, in LPS-polarised M1 macrophages. Thus, exposure to different nanoparticles can modulate, in different ways, the defence/inflammatory capacities of macrophages. A thorough analysis of these biasing effects may shed light on the mechanisms of pathogensis of several diseases based on dysregulation of the immune response (allergies, autoimmunity, tumours).. nanoparticles| inflammation| macrophages| tlr receptors| cytokines| innate immunity|toll-like receptors| signaling pathways| host-defense| inflammation| activation| silica| oligodeoxynucleotides| nanoparticle| disease| mice.	OCT-DEC-2004	nanoparticles| inflammation| macrophages| tlr receptors| cytokines| innate immunity|toll-like receptors| signaling pathways| host-defense| inflammation| activation| silica| oligodeoxynucleotides| nanoparticle| disease| mice	Lucarelli, M; Gatti, AM; Savarino, G; Quattroni, P; Martinelli, L; Monari, E; Boraschi, D	Innate defence functions of macrophages can be biased by nano-sized ceramic and metallic particles		EUROPEAN CYTOKINE NETWORK	nanoparticles; inflammation; macrophages; TLR receptors; cytokines; innate immunity	TOLL-LIKE RECEPTORS; SIGNALING PATHWAYS; HOST-DEFENSE; INFLAMMATION; ACTIVATION; SILICA; OLIGODEOXYNUCLEOTIDES; NANOPARTICLE; DISEASE; MICE	Nano-sized particles of ceramic and metallic materials are generated by high-tech industrial activities, and can be generated from worn-out replacement and prosthetic implants. The interaction with the human body of such nanoparticles has been investigated, with a particular emphasis on innate defence mechanisms. Human macrophages (PMA-differentiated myelomonocytic U-937 cells) were exposed in vitro to non-toxic concentrations of TiO2 SiO2 ZrO2 or Co nanoparticles, and their inflammatory response (expression of TLR receptors and co-receptors, and cytokine production) was examined. Expression of TLR receptors was generally unaffected by exposure to the different nanoparticles, except for some notable cases. Exposure to nanoparticles of ZrO2 (and to a lesser extent TiO2), upregulated expression of viral TLR receptors TLR3 and TLR7. Expression of TLR10 was also increased by TiO2 and ZrO2 nanoparticles. On the other hand, TLR9 expression was decreased by SiO2 nanoparticles, and expression of the co-receptor CD14 was inhibited by Co nanoparticles. Basal and LPS-induced production of cytokines 1L-1beta, TNF-alpha, and 1L-1Ra was examined in macrophages exposed to nanoparticles. SiO2 nanoparticles strongly biased naive macrophages towards inflammation (M1 polarisation), by selectively inducing production of inflammatory cytokines IL-1beta and TNF-alpha. SiO2 nanoparticles also significantly amplified the inflammatory phenotype of LPS-polarised M1 macrophages. Other ceramic nanoparticles had little influence on cytokine production, either in resting macrophages, or in LPS-activated cells. Generally, Co nanoparticles had an overall pro-inflammatory effect on naive macrophages, by reducing anti-inflammatory IL-1Ra and inducing inflammatory TNF-alpha. However, Co nanoparticles reduced production of IL-1beta and IL-1Ra, but not TNF-alpha, in LPS-polarised M1 macrophages. Thus, exposure to different nanoparticles can modulate, in different ways, the defence/inflammatory capacities of macrophages. A thorough analysis of these biasing effects may shed light on the mechanisms of pathogensis of several diseases based on dysregulation of the immune response (allergies, autoimmunity, tumours).	31	77	2004	8		Biochemistry & Molecular Biology; Cell Biology; Immunology
Particulate air pollution and panel studies in children: a systematic review. Background: Panel studies have been used to investigate the short term effects of outdoor particulate air pollution across a wide range of environmental settings. Aims: To systematically review the results of such studies in children, estimate summary measures of effect, and investigate potential sources of heterogeneity. Methods: Studies were identified by searching electronic databases to June 2002, including those where outcomes and particulate level measurements were made at least daily for greater than or equal to 8 weeks, and analysed using an appropriate regression model. Study results were compared using forest plots, and fixed and random effects summary effect estimates obtained. Publication bias was considered using a funnel plot. Results: Twenty two studies were identified, all except two reporting PM10 (24 hour mean) >50 mug. m(-3). Reported effects of PM10 on PEF were widely spread and smaller than those for PM2.5 (fixed effects summary: -0.012 v -0.063 l. min(-1) per mug. m(-3) rise). A similar pattern was evident for symptoms. Random effects models produced larger estimates. Overall, in between-study comparisons, panels of children with diagnosed asthma or pre-existing respiratory symptoms appeared less affected by PM10 levels than those without, and effect estimates were larger where studies were conducted in higher ozone conditions. Larger PM10 effect estimates were obtained from studies using generalised estimating equations to model autocorrelation and where results were derived by pooling subject specific regression coefficients. A funnel plot of PM10 results for PEF was markedly asymmetrical. Conclusions: The majority of identified studies indicate an adverse effect of particulate air pollution that is greater for PM2.5 than PM10. However, results show considerable heterogeneity and there is evidence consistent with publication bias, so limited confidence may be placed on summary estimates of effect. The possibility of interaction between particle and ozone effects merits further investigation, as does variability due to analytical differences that alter the interpretation of final estimates.. peak expiratory flow| chronic respiratory symptoms| time-series analysis| asthmatic-children| methodological issues| fine particles| pm10 pollution| medication use| los-angeles| mexico-city.	APR 1-2004	peak expiratory flow| chronic respiratory symptoms| time-series analysis| asthmatic-children| methodological issues| fine particles| pm10 pollution| medication use| los-angeles| mexico-city	Ward, DJ; Ayres, JG	Particulate air pollution and panel studies in children: a systematic review		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		PEAK EXPIRATORY FLOW; CHRONIC RESPIRATORY SYMPTOMS; TIME-SERIES ANALYSIS; ASTHMATIC-CHILDREN; METHODOLOGICAL ISSUES; FINE PARTICLES; PM10 POLLUTION; MEDICATION USE; LOS-ANGELES; MEXICO-CITY	Background: Panel studies have been used to investigate the short term effects of outdoor particulate air pollution across a wide range of environmental settings. Aims: To systematically review the results of such studies in children, estimate summary measures of effect, and investigate potential sources of heterogeneity. Methods: Studies were identified by searching electronic databases to June 2002, including those where outcomes and particulate level measurements were made at least daily for greater than or equal to 8 weeks, and analysed using an appropriate regression model. Study results were compared using forest plots, and fixed and random effects summary effect estimates obtained. Publication bias was considered using a funnel plot. Results: Twenty two studies were identified, all except two reporting PM10 (24 hour mean) >50 mug. m(-3). Reported effects of PM10 on PEF were widely spread and smaller than those for PM2.5 (fixed effects summary: -0.012 v -0.063 l. min(-1) per mug. m(-3) rise). A similar pattern was evident for symptoms. Random effects models produced larger estimates. Overall, in between-study comparisons, panels of children with diagnosed asthma or pre-existing respiratory symptoms appeared less affected by PM10 levels than those without, and effect estimates were larger where studies were conducted in higher ozone conditions. Larger PM10 effect estimates were obtained from studies using generalised estimating equations to model autocorrelation and where results were derived by pooling subject specific regression coefficients. A funnel plot of PM10 results for PEF was markedly asymmetrical. Conclusions: The majority of identified studies indicate an adverse effect of particulate air pollution that is greater for PM2.5 than PM10. However, results show considerable heterogeneity and there is evidence consistent with publication bias, so limited confidence may be placed on summary estimates of effect. The possibility of interaction between particle and ozone effects merits further investigation, as does variability due to analytical differences that alter the interpretation of final estimates.	52	77	2004	12	10.1136/oem.2003.007088	Public, Environmental & Occupational Health
Pharmacokinetics of [C-14]ciclesonide after oral and intravenous administration to healthy subjects. Background: Ciclesonide is a novel inhaled corticosteroid developed for the treatment of asthma. Objective: To investigate the extent of oral absorption and bioavailability of ciclesonide referenced to an intravenous infusion. This information provides an estimate for the contribution of the swallowed fraction to systemic exposure to ciclesonide after oral inhalation. Methods: In a randomised crossover study, six healthy male subjects (age range 19-40 years) received single doses of 6.9mg (oral administration) and 0.64mg (intravenous administration) of [C-14]ciclesonide, separated by a washout period of at least 14 days. Total radioactivity was determined in whole blood, plasma, urine and faeces. Serum concentrations of ciclesonide and its major metabolite, the pharmacologically active desisobutyryl-ciclesonide (des-CIC), were determined in serum by high-performance liquid chromatography with tandem mass spectrometry detection. Results: After a 10-minute intravenous infusion, the mean half-life for total radioactivity was 45.2 hours. Elimination of des-CIC was fast with a mean elimination half-life of 3.5 hours. After oral administration, the mean half-life for total radioactivity was 27.5 hours. On the basis of a comparison of dose-normalised areas under the curve of total plasma radioactivity versus time, 24.5% of orally administered [C-14]ciclesonide was absorbed. The parent compound ciclesonide was not detected in any of the serum samples after oral administration; serum concentrations of des-CIC were mostly near or below the lower limit of quantification. Thus, systemic bioavailability for des-CIC is <1 % and the absolute bioavailability of ciclesonide is even less than this. [C-14]Ciclesonide showed no retention in red blood cells. The mean cumulative excretion of total radioactivity was almost complete by 120 hours after oral and intravenous administration. Faecal excretion was the predominant route of excretion for total radioactivity after both routes of administration. Single oral and intravenous administration of ciclesonide was well tolerated. Conclusions: Because of an almost complete first-pass metabolism, ciclesonide is undetectable in serum after oral administration. Thus, any ciclesonide swallowed after oral inhalation does not contribute to systemically available ciclesonide or to its active metabolite. Drug-related metabolites are excreted mainly via the faeces, and overall recovery of administered radioactivity is virtually complete after an extended sample collection period.. topical steroid ciclesonide| inhaled glucocorticoids| airway responsiveness| asthma| budesonide| risk| corticosteroids| inhalation.	2004	topical steroid ciclesonide| inhaled glucocorticoids| airway responsiveness| asthma| budesonide| risk| corticosteroids| inhalation	Nave, R; Bethke, TD; van Marle, SP; Zech, K	Pharmacokinetics of [C-14]ciclesonide after oral and intravenous administration to healthy subjects		CLINICAL PHARMACOKINETICS		TOPICAL STEROID CICLESONIDE; INHALED GLUCOCORTICOIDS; AIRWAY RESPONSIVENESS; ASTHMA; BUDESONIDE; RISK; CORTICOSTEROIDS; INHALATION	Background: Ciclesonide is a novel inhaled corticosteroid developed for the treatment of asthma. Objective: To investigate the extent of oral absorption and bioavailability of ciclesonide referenced to an intravenous infusion. This information provides an estimate for the contribution of the swallowed fraction to systemic exposure to ciclesonide after oral inhalation. Methods: In a randomised crossover study, six healthy male subjects (age range 19-40 years) received single doses of 6.9mg (oral administration) and 0.64mg (intravenous administration) of [C-14]ciclesonide, separated by a washout period of at least 14 days. Total radioactivity was determined in whole blood, plasma, urine and faeces. Serum concentrations of ciclesonide and its major metabolite, the pharmacologically active desisobutyryl-ciclesonide (des-CIC), were determined in serum by high-performance liquid chromatography with tandem mass spectrometry detection. Results: After a 10-minute intravenous infusion, the mean half-life for total radioactivity was 45.2 hours. Elimination of des-CIC was fast with a mean elimination half-life of 3.5 hours. After oral administration, the mean half-life for total radioactivity was 27.5 hours. On the basis of a comparison of dose-normalised areas under the curve of total plasma radioactivity versus time, 24.5% of orally administered [C-14]ciclesonide was absorbed. The parent compound ciclesonide was not detected in any of the serum samples after oral administration; serum concentrations of des-CIC were mostly near or below the lower limit of quantification. Thus, systemic bioavailability for des-CIC is <1 % and the absolute bioavailability of ciclesonide is even less than this. [C-14]Ciclesonide showed no retention in red blood cells. The mean cumulative excretion of total radioactivity was almost complete by 120 hours after oral and intravenous administration. Faecal excretion was the predominant route of excretion for total radioactivity after both routes of administration. Single oral and intravenous administration of ciclesonide was well tolerated. Conclusions: Because of an almost complete first-pass metabolism, ciclesonide is undetectable in serum after oral administration. Thus, any ciclesonide swallowed after oral inhalation does not contribute to systemically available ciclesonide or to its active metabolite. Drug-related metabolites are excreted mainly via the faeces, and overall recovery of administered radioactivity is virtually complete after an extended sample collection period.	22	77	2004	8	10.2165/00003088-200443070-00004	Pharmacology & Pharmacy
Pulmonary function, diffusing capacity, and inflammation in healthy and asthmatic subjects exposed to ultrafine particles. Particulate air pollution is associated with asthma exacerbations and increased morbidity and mortality from respiratory causes. Ultrafine particles (particles less than 0.1 mum in diameter) may contribute to these adverse effects because they have a higher predicted pulmonary deposition, greater potential to induce pulmonary inflammation, larger surface area, and enhanced oxidant capacity when compared with larger particles on a mass basis. We hypothesized that ultrafine particle exposure Would induce airway inflammation in susceptible humans. This hypothesis was tested in a series of randomized, double-blind studies by exposing healthy subjects and mild asthmatic subjects to carbon ultrafine particles versus filtered air. Both exposures were delivered via a mouthpiece system during rest and moderate exercise. Healthy subjects were exposed to particle concentrations of 10, 25, and 50 mug/m(3), while asthmatics were exposed to 10 mug/m(3). Lung function and airway inflammation were assessed by symptom scores, pulmonary function tests, and airway nitric oxide parameters. Airway inflammatory cells were measured via induced sputum analysis in several of the protocols. There were no differences in any of these measurements in normal or asthmatic subjects when exposed to ultrafine particles at concentrations of 10 or 25 mug/m(3). However, exposing 16 normal subjects to the higher concentration of 50 mug/m(3) caused a reduction in maximal midexpiratory flow rate (-4.34 +/- 1.78% [ultrafine particles] vs. +1.08 +/- 1.86% [air], p =.042) and carbon monoxide diffusing capacity (-1.76 +/- 0.66 ml/min/mm Hg [ultrafine particles] vs. -0.18 +/- 0.41 ml/min/mm Hg [air], p =.040) at 21 h after exposure. There were no consistent differences in symptoms, induced sputum, or exhaled nitric oxide parameters in any of these studies. These results suggest that exposure to carbon ultrafine particles results in mild small-airways dysfunction together with impaired alveolar gas exchange in normal subjects. These effects do not appear related to airway inflammation. Additional studies are required to confirm these findings in normal subjects, compare them with additional susceptible patient populations, and determine their pathophysiologic mechanisms.. particulate air-pollution| ambient fine particles| emergency-room visits| nasal nitric-oxide| oxidative stress| environmental aerosols| adhesion molecules| human volunteers| diesel exhaust| term exposure.	2004	particulate air-pollution| ambient fine particles| emergency-room visits| nasal nitric-oxide| oxidative stress| environmental aerosols| adhesion molecules| human volunteers| diesel exhaust| term exposure	Pietropaoli, AP; Frampton, MW; Hyde, RW; Morrow, PE; Oberdorster, G; Cox, C; Speers, DM; Frasier, LM; Chalupa, DC; Huang, LS; Utell, MJ	Pulmonary function, diffusing capacity, and inflammation in healthy and asthmatic subjects exposed to ultrafine particles		INHALATION TOXICOLOGY		PARTICULATE AIR-POLLUTION; AMBIENT FINE PARTICLES; EMERGENCY-ROOM VISITS; NASAL NITRIC-OXIDE; OXIDATIVE STRESS; ENVIRONMENTAL AEROSOLS; ADHESION MOLECULES; HUMAN VOLUNTEERS; DIESEL EXHAUST; TERM EXPOSURE	Particulate air pollution is associated with asthma exacerbations and increased morbidity and mortality from respiratory causes. Ultrafine particles (particles less than 0.1 mum in diameter) may contribute to these adverse effects because they have a higher predicted pulmonary deposition, greater potential to induce pulmonary inflammation, larger surface area, and enhanced oxidant capacity when compared with larger particles on a mass basis. We hypothesized that ultrafine particle exposure Would induce airway inflammation in susceptible humans. This hypothesis was tested in a series of randomized, double-blind studies by exposing healthy subjects and mild asthmatic subjects to carbon ultrafine particles versus filtered air. Both exposures were delivered via a mouthpiece system during rest and moderate exercise. Healthy subjects were exposed to particle concentrations of 10, 25, and 50 mug/m(3), while asthmatics were exposed to 10 mug/m(3). Lung function and airway inflammation were assessed by symptom scores, pulmonary function tests, and airway nitric oxide parameters. Airway inflammatory cells were measured via induced sputum analysis in several of the protocols. There were no differences in any of these measurements in normal or asthmatic subjects when exposed to ultrafine particles at concentrations of 10 or 25 mug/m(3). However, exposing 16 normal subjects to the higher concentration of 50 mug/m(3) caused a reduction in maximal midexpiratory flow rate (-4.34 +/- 1.78% [ultrafine particles] vs. +1.08 +/- 1.86% [air], p =.042) and carbon monoxide diffusing capacity (-1.76 +/- 0.66 ml/min/mm Hg [ultrafine particles] vs. -0.18 +/- 0.41 ml/min/mm Hg [air], p =.040) at 21 h after exposure. There were no consistent differences in symptoms, induced sputum, or exhaled nitric oxide parameters in any of these studies. These results suggest that exposure to carbon ultrafine particles results in mild small-airways dysfunction together with impaired alveolar gas exchange in normal subjects. These effects do not appear related to airway inflammation. Additional studies are required to confirm these findings in normal subjects, compare them with additional susceptible patient populations, and determine their pathophysiologic mechanisms.	57	77	2004	14	10.1080/08958370490443079	Toxicology
Allergic rhinitis: Systemic inflammation and implications for management. Allergic rhinitis triggers a systemic increase of inflammation. Within minutes of allergen exposure, immune cells release histamine, proteases, cysteinyl leukotrienes, prostaglandins, and cytokines. Some produce the early symptoms, while others augment the production, systemic circulation, and subsequent infiltration of the nasal mucosa with inflammatory cells that sustain the symptoms. Systemic circulation of inflammatory cells permits their infiltration into other tissues where chemoattractant and adhesion molecules already exist. Consequently, allergic rhinitis is linked to comorbid conditions: asthma, chronic hyperplastic eosinophilic sinusitis, nasal pollyposis, and serous otitis media. Effective therapy should be directed at underlying inflammation and its systemic manifestations. It should improve the rhinitis and the comorbid conditions. Antihistamines relieve early symptoms by blocking basophil- and mast cell-generated histamine, but they do not significantly influence the pro-inflammatory loop. They are often little better than placebo. Oral corticosteroids provide the systemic anti-inflammatory efficacy, but their toxicity precludes such an approach. Intranasal corticosteroids effectively target the local inflammatory processes of rhinitis, reducing local inflammatory cells within the nares, but they do not directly access tissues involved in the comorbid conditions. Leukotriene modifiers have both systemic anti-inflammatory effects and an acceptable safety profile.. allergic rhinitis| asthma| chronic hyperplastic eosinophilic sinusitis| eosinophils| leukotrienes| cytokines| inflammation|placebo-controlled trial| chronic hyperplastic sinusitis| adhesion molecule expression| receptor-mediated mechanism| chronic maxillary sinusitis| messenger-rna expression| chronic-fatigue-syndrome| late asthmatic response| bone-marrow| double-blind.	DEC-2003	allergic rhinitis| asthma| chronic hyperplastic eosinophilic sinusitis| eosinophils| leukotrienes| cytokines| inflammation|placebo-controlled trial| chronic hyperplastic sinusitis| adhesion molecule expression| receptor-mediated mechanism| chronic maxillary sinusitis| messenger-rna expression| chronic-fatigue-syndrome| late asthmatic response| bone-marrow| double-blind	Borish, L	Allergic rhinitis: Systemic inflammation and implications for management		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergic rhinitis; asthma; chronic hyperplastic eosinophilic sinusitis; eosinophils; leukotrienes; cytokines; inflammation	PLACEBO-CONTROLLED TRIAL; CHRONIC HYPERPLASTIC SINUSITIS; ADHESION MOLECULE EXPRESSION; RECEPTOR-MEDIATED MECHANISM; CHRONIC MAXILLARY SINUSITIS; MESSENGER-RNA EXPRESSION; CHRONIC-FATIGUE-SYNDROME; LATE ASTHMATIC RESPONSE; BONE-MARROW; DOUBLE-BLIND	Allergic rhinitis triggers a systemic increase of inflammation. Within minutes of allergen exposure, immune cells release histamine, proteases, cysteinyl leukotrienes, prostaglandins, and cytokines. Some produce the early symptoms, while others augment the production, systemic circulation, and subsequent infiltration of the nasal mucosa with inflammatory cells that sustain the symptoms. Systemic circulation of inflammatory cells permits their infiltration into other tissues where chemoattractant and adhesion molecules already exist. Consequently, allergic rhinitis is linked to comorbid conditions: asthma, chronic hyperplastic eosinophilic sinusitis, nasal pollyposis, and serous otitis media. Effective therapy should be directed at underlying inflammation and its systemic manifestations. It should improve the rhinitis and the comorbid conditions. Antihistamines relieve early symptoms by blocking basophil- and mast cell-generated histamine, but they do not significantly influence the pro-inflammatory loop. They are often little better than placebo. Oral corticosteroids provide the systemic anti-inflammatory efficacy, but their toxicity precludes such an approach. Intranasal corticosteroids effectively target the local inflammatory processes of rhinitis, reducing local inflammatory cells within the nares, but they do not directly access tissues involved in the comorbid conditions. Leukotriene modifiers have both systemic anti-inflammatory effects and an acceptable safety profile.	131	77	2003	11	10.1016/j.jaci.2003.90.015	Allergy; Immunology
Chlorine-induced injury to the airways in mice. Exposure to chlorine gas (Cl-2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl-2 and 2 and 7 days after inhalation of 400 ppm Cl-2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl-2. Responsiveness after inhalation of 400 ppm Cl-2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl-2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl-2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl-2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine.. chlorine| inducible nitric oxide synthase| nitric oxide| oxidative injury|exhaled nitric-oxide| acute lung injury| longitudinal distribution| dysfunction syndrome| protein nitration| persistent asthma| ozone| exposure| inflammation| rats.	SEP 1-2003	chlorine| inducible nitric oxide synthase| nitric oxide| oxidative injury|exhaled nitric-oxide| acute lung injury| longitudinal distribution| dysfunction syndrome| protein nitration| persistent asthma| ozone| exposure| inflammation| rats	Martin, JG; Campbell, HR; Iijima, H; Gautrin, D; Malo, JL; Eidelman, DH; Hamid, Q; Maghni, K	Chlorine-induced injury to the airways in mice		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	chlorine; inducible nitric oxide synthase; nitric oxide; oxidative injury	EXHALED NITRIC-OXIDE; ACUTE LUNG INJURY; LONGITUDINAL DISTRIBUTION; DYSFUNCTION SYNDROME; PROTEIN NITRATION; PERSISTENT ASTHMA; OZONE; EXPOSURE; INFLAMMATION; RATS	Exposure to chlorine gas (Cl-2) causes occupational asthma that we hypothesized occurs through the induction of airway inflammation and airway hyperresponsiveness by oxidative damage. Respiratory mechanics and airway responsiveness to methacholine were assessed in A/J mice 24 hours after a 5-minute exposure to 100, 200, 400, or 800 ppm Cl-2 and 2 and 7 days after inhalation of 400 ppm Cl-2. Airway responsiveness was higher 24 hours after 400 and 800 ppm Cl-2. Responsiveness after inhalation of 400 ppm Cl-2 returned to normal by 2 days but was again elevated at 7 days. Airway epithelial loss, patchy alveolar damage, proteinaceous exudates, and inflammatory cells within alveolar walls were observed in animals exposed to 800 ppm Cl-2. Macrophages, granulocytes, epithelial cells, and nitrate/nitrite levels increased in lung lavage fluid. Increased inducible nitric oxide synthase expression and oxidation of lung proteins were observed. Epithelial cells and alveolar macrophages from mice exposed to 800 ppm Cl-2 stained for 3-nitrotyrosine residues. Inhibition of inducible nitric oxide synthase with 1400W (1 mg/kg) abrogated the Cl-2-induced changes in responsiveness. We conclude that chlorine exposure causes functional and pathological changes in the airways associated with oxidative stress. Inducible nitric oxide synthase is involved in the induction of changes in responsiveness to methacholine.	36	77	2003	7	10.1164/rccm.200201-021OC	General & Internal Medicine; Respiratory System
Which factors explain the lower prevalence of atopy amongst farmers' children?. Background: The inverse association between farming and atopy in children has been attributed to microbial exposure, especially through livestock. Very little is known about other potential explanatory factors. Objective: To explore potential differences in lifestyle and environmental factors between farmer and non-farmer families, and whether these factors could explain the association between farming and childhood atopy. Methods: A cross-sectional study, including 366 farmers' and 344 non-farmers' children in eastern Finland. Information regarding exposure and background characteristics was gathered by a written questionnaire. Atopy was defined as having one or more positive skin prick test reactions (> 3 mm) against the six common aeroallergens. Results: Regardless of the current farming type, atopy was less frequent among the farmers' children than the non-farmers' children (aOR 0.56, 95% CI 0.40-0.78). Remarkable differences were seen in many lifestyle factors (including diet) between the farmer and non-farmer families, but only a few of the explored factors were associated with atopy. The frequency of current livestock contacts seemed to have an inverse, dose-dependent association with atopy (aOR 0.46, 95% CI 0.22-0.97 for daily vs. no contact). Having lived on a dairy farm in infancy (aOR 0.51, 95% CI 0.28-0.93), or having had cats or dogs in infancy (aOR 0.60, 95% CI 0.42-0.85), decreased the risk of atopy at school age. The inverse association between farming and atopy was not explained by the sociodemographic factors, or by differences in conventional risk factors of atopy. Animal contacts explained partially, but not completely, the association. Conclusion Higher frequency of animal contacts is one factor, but probably not the only one, explaining the inverse association of farming and atopy in children. The importance of early life exposures may have recently been over-emphasized, and current exposures discounted, when studying the risk factors of childhood atopy.. atopy| children| epidemiology| farm| risk factors| skin prick test|fatty-acids| hay-fever| allergic sensitization| birth cohort| asthma| childhood| endotoxin| exposure| environment| community.	APR-2003	atopy| children| epidemiology| farm| risk factors| skin prick test|fatty-acids| hay-fever| allergic sensitization| birth cohort| asthma| childhood| endotoxin| exposure| environment| community	Remes, ST; Iivanainen, K; Koskela, H; Pekkanen, J	Which factors explain the lower prevalence of atopy amongst farmers' children?		CLINICAL AND EXPERIMENTAL ALLERGY	atopy; children; epidemiology; farm; risk factors; skin prick test	FATTY-ACIDS; HAY-FEVER; ALLERGIC SENSITIZATION; BIRTH COHORT; ASTHMA; CHILDHOOD; ENDOTOXIN; EXPOSURE; ENVIRONMENT; COMMUNITY	Background: The inverse association between farming and atopy in children has been attributed to microbial exposure, especially through livestock. Very little is known about other potential explanatory factors. Objective: To explore potential differences in lifestyle and environmental factors between farmer and non-farmer families, and whether these factors could explain the association between farming and childhood atopy. Methods: A cross-sectional study, including 366 farmers' and 344 non-farmers' children in eastern Finland. Information regarding exposure and background characteristics was gathered by a written questionnaire. Atopy was defined as having one or more positive skin prick test reactions (> 3 mm) against the six common aeroallergens. Results: Regardless of the current farming type, atopy was less frequent among the farmers' children than the non-farmers' children (aOR 0.56, 95% CI 0.40-0.78). Remarkable differences were seen in many lifestyle factors (including diet) between the farmer and non-farmer families, but only a few of the explored factors were associated with atopy. The frequency of current livestock contacts seemed to have an inverse, dose-dependent association with atopy (aOR 0.46, 95% CI 0.22-0.97 for daily vs. no contact). Having lived on a dairy farm in infancy (aOR 0.51, 95% CI 0.28-0.93), or having had cats or dogs in infancy (aOR 0.60, 95% CI 0.42-0.85), decreased the risk of atopy at school age. The inverse association between farming and atopy was not explained by the sociodemographic factors, or by differences in conventional risk factors of atopy. Animal contacts explained partially, but not completely, the association. Conclusion Higher frequency of animal contacts is one factor, but probably not the only one, explaining the inverse association of farming and atopy in children. The importance of early life exposures may have recently been over-emphasized, and current exposures discounted, when studying the risk factors of childhood atopy.	29	77	2003	8	10.1046/j.1365-2222.2003.01566.x	Allergy; Immunology
Allergy, atopy, and cancer: A prospective study of the 1981 Busselton cohort. The associations among certain allergic disorders, atopy upon skin-prick testing, and specific cancers were evaluated in a prospective study. Information regarding history of asthma and hay fever was collected by questionnaire from 3,308 cancer-free participants in the 1981 Busselton Health Survey. A subset of 1,005 participants also underwent skin-prick testing. The cohort was followed for a new diagnosis of cancer or death until the end of 1999. Cox proportional hazards regression analysis was used to estimate adjusted hazard ratios (relative risks) for breast, prostate, colorectal, lung, and hematologic cancers and melanoma. Having a skin reaction to house dust mites nearly tripled the risk of prostate cancer (relative risk=2.90, 95% confidence interval: 1.26, 6.68). History of asthma and hay fever were associated with a trend toward a reduced risk of colorectal cancer and increased risk of leukemia, but these results were not statistically significant. Hay fever was associated with melanoma risk in men but not in women. No association was found between breast and lung cancers and allergic disorders or atopy.. allergy and immunology| asthma| hypersensitivity| immediate| neoplasms| skin tests|colorectal-cancer| population| asthma| risk| prevalence| mortality| diseases.	APR 1-2003	allergy and immunology| asthma| hypersensitivity| immediate| neoplasms| skin tests|colorectal-cancer| population| asthma| risk| prevalence| mortality| diseases	Talbot-Smith, A; Fritschi, L; Divitini, ML; Mallon, DFJ; Knuiman, MW	Allergy, atopy, and cancer: A prospective study of the 1981 Busselton cohort		AMERICAN JOURNAL OF EPIDEMIOLOGY	allergy and immunology; asthma; hypersensitivity; immediate; neoplasms; skin tests	COLORECTAL-CANCER; POPULATION; ASTHMA; RISK; PREVALENCE; MORTALITY; DISEASES	The associations among certain allergic disorders, atopy upon skin-prick testing, and specific cancers were evaluated in a prospective study. Information regarding history of asthma and hay fever was collected by questionnaire from 3,308 cancer-free participants in the 1981 Busselton Health Survey. A subset of 1,005 participants also underwent skin-prick testing. The cohort was followed for a new diagnosis of cancer or death until the end of 1999. Cox proportional hazards regression analysis was used to estimate adjusted hazard ratios (relative risks) for breast, prostate, colorectal, lung, and hematologic cancers and melanoma. Having a skin reaction to house dust mites nearly tripled the risk of prostate cancer (relative risk=2.90, 95% confidence interval: 1.26, 6.68). History of asthma and hay fever were associated with a trend toward a reduced risk of colorectal cancer and increased risk of leukemia, but these results were not statistically significant. Hay fever was associated with melanoma risk in men but not in women. No association was found between breast and lung cancers and allergic disorders or atopy.	36	77	2003	7	10.1093/aje/kwg020	Public, Environmental & Occupational Health
Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity. This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study, Over a 6-month period (November 1, 1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-posftive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age less than or equal to 33 weeks or 34-35 weeks, as compared to those with agestational age > 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV 4 was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tractinfection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease. (C) Wiley-Liss, Inc.. respiratory syncytial virus| bronchiolitis| epidemiology| wheezing| pneumonia| passive tobacco smoke| gestational age| birth order| birth weight|investigators collaborative network| canadian children| viral-infection| bronchiolitis| rehospitalization| management| gestation| illnesses| smoking| allergy.	JUN-2002	respiratory syncytial virus| bronchiolitis| epidemiology| wheezing| pneumonia| passive tobacco smoke| gestational age| birth order| birth weight|investigators collaborative network| canadian children| viral-infection| bronchiolitis| rehospitalization| management| gestation| illnesses| smoking| allergy	Lanari, M; Giovannini, M; Giuffre, L; Marini, A; Rondini, G; Rossi, GA; Merolla, R; Zuccotti, GV; Salvioli, GP	Prevalence of respiratory syncytial virus infection in Italian infants hospitalized for acute lower respiratory tract infections, and association between respiratory syncytial virus infection risk factors and disease severity		PEDIATRIC PULMONOLOGY	respiratory syncytial virus; bronchiolitis; epidemiology; wheezing; pneumonia; passive tobacco smoke; gestational age; birth order; birth weight	INVESTIGATORS COLLABORATIVE NETWORK; CANADIAN CHILDREN; VIRAL-INFECTION; BRONCHIOLITIS; REHOSPITALIZATION; MANAGEMENT; GESTATION; ILLNESSES; SMOKING; ALLERGY	This study was designed to collect data on the prevalence of respiratory syncytial virus (RSV) infection in Italy in infants hospitalized for lower respiratory tract infections, and to evaluate which of the recognized risk factors might be associated with disease severity. Thirty-two centers throughout Italy participated in the study, Over a 6-month period (November 1, 1999 to April 30, 2000), we evaluated all children < 2 years of age hospitalized for lower respiratory tract infections. All subjects were tested for RSV within 24 hr of hospitalization by using an immuno-enzymatic diagnostic test (Abbott Testpack, RSV). Logistic regression was used to identify the factors that might be associated with more severe disease or could increase the likelihood of RSV positivity in hospitalized infants. Out of a total of 1,232 children enrolled, 40.6% were found to be RSV-posftive (RSV+). The peak of the RSV epidemic occurred in February, while the lowest prevalence of RSV positivity was seen in November (P < 0.05). A high proportion of study subjects had low birth weight and low gestational age. The clinical diagnosis at hospitalization was bronchiolitis in 66.7%, pneumonia in 15.3%, and wheezy bronchitis in 18.1%. In the bronchiolitis group, a higher prevalence of RSV+ was found in patients with gestational age less than or equal to 33 weeks or 34-35 weeks, as compared to those with agestational age > 36 weeks (P < 0.04). No differences were found in the proportion of RSV+ patients in the three gestational age subgroups with pneumonia and wheezy bronchitis (P > 0.05, each comparison). Independent of the clinical diagnosis at admission, RSV infection was associated with more severe respiratory impairment. Environmental smoke exposure was higher in subjects with bronchiolitis than in those with wheezy bronchitis (P < 0.04), and RSV 4 was positively related with the birth order (P < 0.05). The presence of older siblings and birth order plays an important role in RSV infection. The collected data show that, in Italy, RSV is an important cause of lower respiratory tractinfection in infants. Gestational age, birth order, birth weight, and exposure to tobacco smoke affected the prevalence and severity of RSV-related lower respiratory tract disease. (C) Wiley-Liss, Inc.	38	77	2002	8	10.1002/ppul.10052	Pediatrics; Respiratory System
Localization, release and bioavailability of pollen allergens: the influence of environmental factors. Allergens are integral constituents of plants or animals and their normal functions and localization are being characterized. To trigger responses in humans, allergens must become bioavailable and the role of air pollutants - for example diesel-exhaust particles - in this process is causing concern. Finally, the fact that some pollen releases eicosanoid-like proinflammatory mediators may have wide implications.. phleum-pratense pollen| grass-pollen| air-pollution| major allergens| lolium-perenne| electron-microscopy| wall proteins| asthma| particles| aerosol.	DEC-2001	phleum-pratense pollen| grass-pollen| air-pollution| major allergens| lolium-perenne| electron-microscopy| wall proteins| asthma| particles| aerosol	Behrendt, H; Beckert, WM	Localization, release and bioavailability of pollen allergens: the influence of environmental factors		CURRENT OPINION IN IMMUNOLOGY		PHLEUM-PRATENSE POLLEN; GRASS-POLLEN; AIR-POLLUTION; MAJOR ALLERGENS; LOLIUM-PERENNE; ELECTRON-MICROSCOPY; WALL PROTEINS; ASTHMA; PARTICLES; AEROSOL	Allergens are integral constituents of plants or animals and their normal functions and localization are being characterized. To trigger responses in humans, allergens must become bioavailable and the role of air pollutants - for example diesel-exhaust particles - in this process is causing concern. Finally, the fact that some pollen releases eicosanoid-like proinflammatory mediators may have wide implications.	51	77	2001	7	10.1016/S0952-7915(01)00283-7	Immunology
Grass pollen immunotherapy inhibits seasonal increases in basophils and eosinophils in the nasal epithelium. Background Symptoms of allergic rhinitis are accompanied by infiltration of the nasal mucosa with inflammatory cells, predominantly eosinophils and metachromatic cells (basophils and mast cells). Specific immunotherapy (IT) reduces mucosal eosinophilia and numbers of metachromatic cells in the epithelium. A specific marker distinguishing basophils from mast cells was recently developed. Objectives The basophil-specific manoclanal antibody 2D7 was used to determine the influence of subcutaneous IT on numbers of nasal mucosal basophils compared with the effects of IT on neutrophils, eosinophils and mast cells. Method During a randomized, placebo-controlled trial of grass pollen IT in 44 adults with severe summer hay fever, nasal biopsies were taken at baseline, out of the pollen season, and at the peak of the pollen season following 2 years treatment. Biopsies were processed for immunohistochemistry far basophils (2D7(+)), mast cells (AA1(+)), eosinophils (MBP+) and neutrophils (neutrophil elastase(+)). Results In placebo-treated (PL) patients there were significant seasonal increases in basophils (P<0.01), mast cells (P<0.05) and eosinophils (P=0.002) irt the nasal submucosa. In IT-treated patients significant increases in 2D7 cells (P<0.01) and eosinophils (P=0.01) but not AA1(+) cells (P=0.9) were observed. These differences were significant between groups for eosinophils (P<0.05). In the epithelium there were seasonal increases in AA1(+) cells and eosinophils in both groups (PL: P<0.01, IT: P<0.05 far both). The between-group difference was significant for eosinophils (P=0.05). Basophils were observed in the epithelium of six out of 17 in the placebo group and one out of 20 in the IT group (P=0.03). Neutrophil numbers remained constant in both epithelium and submucosa. Conclusion Successful grass pollen immunotherapy was associated with inhibition of seasonal increases in basophils and eosinophils, but not mast cells or neutrophils within the nasal epithelium. Immunotherapy may act, at least in part, by reducing seasonal recruitment of basophils and eosinophils into the epithelium.. allergic rhinitis| immunotherapy| immunohistochemistry| basophil| mast cell| eosinophil| neutrophil|natural allergen exposure| human blood basophils| mast-cells| messenger-rna| induced rhinitis| hay-fever| topical corticosteroids| metachromatic cells| antigen challenge| t-lymphocytes.	NOV-2001	allergic rhinitis| immunotherapy| immunohistochemistry| basophil| mast cell| eosinophil| neutrophil|natural allergen exposure| human blood basophils| mast-cells| messenger-rna| induced rhinitis| hay-fever| topical corticosteroids| metachromatic cells| antigen challenge| t-lymphocytes	Wilson, DR; Irani, AM; Walker, SM; Jacobson, MR; Mackay, IS; Schwartz, LB; Durham, SR	Grass pollen immunotherapy inhibits seasonal increases in basophils and eosinophils in the nasal epithelium		CLINICAL AND EXPERIMENTAL ALLERGY	allergic rhinitis; immunotherapy; immunohistochemistry; basophil; mast cell; eosinophil; neutrophil	NATURAL ALLERGEN EXPOSURE; HUMAN BLOOD BASOPHILS; MAST-CELLS; MESSENGER-RNA; INDUCED RHINITIS; HAY-FEVER; TOPICAL CORTICOSTEROIDS; METACHROMATIC CELLS; ANTIGEN CHALLENGE; T-LYMPHOCYTES	Background Symptoms of allergic rhinitis are accompanied by infiltration of the nasal mucosa with inflammatory cells, predominantly eosinophils and metachromatic cells (basophils and mast cells). Specific immunotherapy (IT) reduces mucosal eosinophilia and numbers of metachromatic cells in the epithelium. A specific marker distinguishing basophils from mast cells was recently developed. Objectives The basophil-specific manoclanal antibody 2D7 was used to determine the influence of subcutaneous IT on numbers of nasal mucosal basophils compared with the effects of IT on neutrophils, eosinophils and mast cells. Method During a randomized, placebo-controlled trial of grass pollen IT in 44 adults with severe summer hay fever, nasal biopsies were taken at baseline, out of the pollen season, and at the peak of the pollen season following 2 years treatment. Biopsies were processed for immunohistochemistry far basophils (2D7(+)), mast cells (AA1(+)), eosinophils (MBP+) and neutrophils (neutrophil elastase(+)). Results In placebo-treated (PL) patients there were significant seasonal increases in basophils (P<0.01), mast cells (P<0.05) and eosinophils (P=0.002) irt the nasal submucosa. In IT-treated patients significant increases in 2D7 cells (P<0.01) and eosinophils (P=0.01) but not AA1(+) cells (P=0.9) were observed. These differences were significant between groups for eosinophils (P<0.05). In the epithelium there were seasonal increases in AA1(+) cells and eosinophils in both groups (PL: P<0.01, IT: P<0.05 far both). The between-group difference was significant for eosinophils (P=0.05). Basophils were observed in the epithelium of six out of 17 in the placebo group and one out of 20 in the IT group (P=0.03). Neutrophil numbers remained constant in both epithelium and submucosa. Conclusion Successful grass pollen immunotherapy was associated with inhibition of seasonal increases in basophils and eosinophils, but not mast cells or neutrophils within the nasal epithelium. Immunotherapy may act, at least in part, by reducing seasonal recruitment of basophils and eosinophils into the epithelium.	41	77	2001	9	10.1046/j.1365-2222.2001.01231.x	Allergy; Immunology
Oxidative stress status during exposure to propofol, sevoflurane and desflurane. We evaluated the circulating and lung oxidative status during general anesthesia established with propofol, sevoflurane, or desflurane in mechanically ventilated swines. Blood samples and bronchoalveolar lavage fluid (BAL) specimens were respectively performed via an internal jugular vein catheter and a nonbronchoscopic BAL for baseline oxidative activity measurements: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX). A 4-h general anesthesia was then performed in the three groups of 10 swine: the Propofol group received 8 mg(.)kg(-1.)h(-1) of IV propofol as the sole anesthetic; the Desflurane group received 1.0 minimum alveolar concentration of desflurane; and the Sevoflurane group received 1.0 minimum alveolar concentration of sevoflurane. We observed significantly larger levels of MDA in plasma and BAL during desflurane exposure than with the other anesthetics. We also observed smaller concentrations of circulating GPX and alveolar GPX We found a significant decrease for MDA measurements in the plasma and the pulmonary lavage during propofol anesthesia. We also found larger values of GPX measurements in the serum and the pulmonary lavage. No significant changes were observed when animals were exposed to sevoflurane. No significant changes were found for circulating concentrations of SOD during exposure to all anesthetics. In this mechanically ventilated swine model, desflurane seemed to induce a local and systemic oxidative stress, whereas propofol and sevoflurane were more likely to have antioxidant properties.. alveolar macrophages| proinflammatory cytokines| bronchoalveolar lavage| antioxidant status| expired breath| rat| expression| anesthesia| asthma.	OCT-2001	alveolar macrophages| proinflammatory cytokines| bronchoalveolar lavage| antioxidant status| expired breath| rat| expression| anesthesia| asthma	Allaouchiche, B; Debon, R; Goudable, J; Chassard, D; Duflo, F	Oxidative stress status during exposure to propofol, sevoflurane and desflurane		ANESTHESIA AND ANALGESIA		ALVEOLAR MACROPHAGES; PROINFLAMMATORY CYTOKINES; BRONCHOALVEOLAR LAVAGE; ANTIOXIDANT STATUS; EXPIRED BREATH; RAT; EXPRESSION; ANESTHESIA; ASTHMA	We evaluated the circulating and lung oxidative status during general anesthesia established with propofol, sevoflurane, or desflurane in mechanically ventilated swines. Blood samples and bronchoalveolar lavage fluid (BAL) specimens were respectively performed via an internal jugular vein catheter and a nonbronchoscopic BAL for baseline oxidative activity measurements: malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX). A 4-h general anesthesia was then performed in the three groups of 10 swine: the Propofol group received 8 mg(.)kg(-1.)h(-1) of IV propofol as the sole anesthetic; the Desflurane group received 1.0 minimum alveolar concentration of desflurane; and the Sevoflurane group received 1.0 minimum alveolar concentration of sevoflurane. We observed significantly larger levels of MDA in plasma and BAL during desflurane exposure than with the other anesthetics. We also observed smaller concentrations of circulating GPX and alveolar GPX We found a significant decrease for MDA measurements in the plasma and the pulmonary lavage during propofol anesthesia. We also found larger values of GPX measurements in the serum and the pulmonary lavage. No significant changes were observed when animals were exposed to sevoflurane. No significant changes were found for circulating concentrations of SOD during exposure to all anesthetics. In this mechanically ventilated swine model, desflurane seemed to induce a local and systemic oxidative stress, whereas propofol and sevoflurane were more likely to have antioxidant properties.	19	77	2001	5	10.1097/00000539-200110000-00036	Anesthesiology
Home dampness, current allergic diseases, and respiratory infections among young adults. Background-The relation between home dampness and respiratory symptoms among adults is well confirmed, but data on specific allergic diseases and respiratory infections is more limited. Individual factors that may enhance susceptibility to the effects of home dampness are mainly unknown. Methods-The association between home dampness and current physician diagnosed asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, common colds, and bacterial respiratory infections was studied in a questionnaire survey of 10 667 Finnish first year university students aged 18-25 years. The dampness categories analysed were visible mould and visible mould or damp stains or water damage during the last year. In multivariate analyses adjustment was made for parental education, active and passive smoking, type and place of residence, pets, and wall to wall carpets. The interaction effect of atopic heredity and dampness was investigated. Results-Visible mould or damp stains or water damage was reported by 15.0% of the respondents. In multivariate models there was a positive association between home dampness and current asthma, allergic rhinitis, and atopic dermatitis, as well as common colds greater than or equal to4 times per year and other respiratory infections, but not between home dampness and allergic conjunctivitis. The strongest association was found between exposure to visible mould and asthma (OR 2.21, 95% CI 1.48 to 3.28) and common colds (OR 1.49, 95% CI 1.18 to 1.87). The risk of current asthma in damp homes was highest among subjects with atopic heredity. Conclusions-The risk of current asthma, allergic rhinitis, and atopic dermatitis was higher in damp homes. Of the respiratory infections, the risk of common colds was most clearly increased.. asthma| allergic rhinitis| atopic dermatitis| dampness|house-dust mite| hay-fever| asthma| children| sensitization| childhood| symptoms| health| molds| inflammation.	JUN-2001	asthma| allergic rhinitis| atopic dermatitis| dampness|house-dust mite| hay-fever| asthma| children| sensitization| childhood| symptoms| health| molds| inflammation	Kilpelainen, M; Terho, EO; Helenius, H; Koskenvuo, M	Home dampness, current allergic diseases, and respiratory infections among young adults		THORAX	asthma; allergic rhinitis; atopic dermatitis; dampness	HOUSE-DUST MITE; HAY-FEVER; ASTHMA; CHILDREN; SENSITIZATION; CHILDHOOD; SYMPTOMS; HEALTH; MOLDS; INFLAMMATION	Background-The relation between home dampness and respiratory symptoms among adults is well confirmed, but data on specific allergic diseases and respiratory infections is more limited. Individual factors that may enhance susceptibility to the effects of home dampness are mainly unknown. Methods-The association between home dampness and current physician diagnosed asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, common colds, and bacterial respiratory infections was studied in a questionnaire survey of 10 667 Finnish first year university students aged 18-25 years. The dampness categories analysed were visible mould and visible mould or damp stains or water damage during the last year. In multivariate analyses adjustment was made for parental education, active and passive smoking, type and place of residence, pets, and wall to wall carpets. The interaction effect of atopic heredity and dampness was investigated. Results-Visible mould or damp stains or water damage was reported by 15.0% of the respondents. In multivariate models there was a positive association between home dampness and current asthma, allergic rhinitis, and atopic dermatitis, as well as common colds greater than or equal to4 times per year and other respiratory infections, but not between home dampness and allergic conjunctivitis. The strongest association was found between exposure to visible mould and asthma (OR 2.21, 95% CI 1.48 to 3.28) and common colds (OR 1.49, 95% CI 1.18 to 1.87). The risk of current asthma in damp homes was highest among subjects with atopic heredity. Conclusions-The risk of current asthma, allergic rhinitis, and atopic dermatitis was higher in damp homes. Of the respiratory infections, the risk of common colds was most clearly increased.	29	77	2001	6	10.1136/thorax.56.6.462	Respiratory System
Quantitation of the major fungal allergens, Alt a 1 and Asp f 1, in commercial allergenic products. Background: Alternaria is one of the most important fungi associated with allergic disease, whereas Aspergillus fumigatus is involved in a broad spectrum of pulmonary diseases. Currently, fungal extracts used for diagnosis in the United States are unstandardized, and their allergenic content cannot be compared directly. Objective: The goal of this study was to compare the variability of major allergen levels among US allergenic products derived from fungi: specifically, Alt a 1 levels in Alternaria alternata extracts, and Asp f 1 levels in A fumigatus extracts. Methods: A novel a-site monoclonal antibody ELISA was used for measuring Alt a 1 using recombinant Alt a 1 as a standard. Asp fl was also measured by ELISA, Allergenic products produced by 8 US manufacturers over a 2-year period were compared, as were multiple lots produced by a single company, Results: Alt a 1 levels in Alternaria extracts from 8 companies produced in 1998 and 1999 ranged from less than 0.01 to 6.09 mug/mL (mean 1.4 +/- 1.6 mug/mL, n = 15), In general, Alt al levels were consistent within and between companies (1.4 +/- 1.1 mug/mL, n = 27), with 21 of 32 (66%) of all extracts tested containing 0.7 to 2 mug/mL Alt a 1, Aspergillus extracts showed much greater variability in Asp fl levels, with extracts from 8 companies containing from less than 0.1 to 64 mug/mL Asp fl (mean 16.3 +/- 23.9 mug/mL, n = 15), Overall variability was greater for Aspergillus products within and between manufacturers (22 +/- 22 mug/mL Asp f 1, a = 20), Conclusions: ELISA-based assays for specific allergens showed greater consistency among allergenic products derived from Alternaria than from Aspergillus, These assays should facilitate improved quality control and standardization of fungal allergen extracts and lead to the development of more consistent products for clinical use.. alternaria| aspergillus| allergen exposure| recombinant allergens| fungi| asthma|school-age-children| alternaria-alternata| bronchial hyperresponsiveness| aspergillus-fumigatus| childhood asthma| a-i| sensitization| extracts| cladosporium| association.	APR-2001	alternaria| aspergillus| allergen exposure| recombinant allergens| fungi| asthma|school-age-children| alternaria-alternata| bronchial hyperresponsiveness| aspergillus-fumigatus| childhood asthma| a-i| sensitization| extracts| cladosporium| association	Vailes, L; Sridhara, S; Cromwell, O; Weber, B; Breitenbach, M; Chapman, M	Quantitation of the major fungal allergens, Alt a 1 and Asp f 1, in commercial allergenic products		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Alternaria; Aspergillus; allergen exposure; recombinant allergens; fungi; asthma	SCHOOL-AGE-CHILDREN; ALTERNARIA-ALTERNATA; BRONCHIAL HYPERRESPONSIVENESS; ASPERGILLUS-FUMIGATUS; CHILDHOOD ASTHMA; A-I; SENSITIZATION; EXTRACTS; CLADOSPORIUM; ASSOCIATION	Background: Alternaria is one of the most important fungi associated with allergic disease, whereas Aspergillus fumigatus is involved in a broad spectrum of pulmonary diseases. Currently, fungal extracts used for diagnosis in the United States are unstandardized, and their allergenic content cannot be compared directly. Objective: The goal of this study was to compare the variability of major allergen levels among US allergenic products derived from fungi: specifically, Alt a 1 levels in Alternaria alternata extracts, and Asp f 1 levels in A fumigatus extracts. Methods: A novel a-site monoclonal antibody ELISA was used for measuring Alt a 1 using recombinant Alt a 1 as a standard. Asp fl was also measured by ELISA, Allergenic products produced by 8 US manufacturers over a 2-year period were compared, as were multiple lots produced by a single company, Results: Alt a 1 levels in Alternaria extracts from 8 companies produced in 1998 and 1999 ranged from less than 0.01 to 6.09 mug/mL (mean 1.4 +/- 1.6 mug/mL, n = 15), In general, Alt al levels were consistent within and between companies (1.4 +/- 1.1 mug/mL, n = 27), with 21 of 32 (66%) of all extracts tested containing 0.7 to 2 mug/mL Alt a 1, Aspergillus extracts showed much greater variability in Asp fl levels, with extracts from 8 companies containing from less than 0.1 to 64 mug/mL Asp fl (mean 16.3 +/- 23.9 mug/mL, n = 15), Overall variability was greater for Aspergillus products within and between manufacturers (22 +/- 22 mug/mL Asp f 1, a = 20), Conclusions: ELISA-based assays for specific allergens showed greater consistency among allergenic products derived from Alternaria than from Aspergillus, These assays should facilitate improved quality control and standardization of fungal allergen extracts and lead to the development of more consistent products for clinical use.	35	77	2001	6		Allergy; Immunology
Long-term follow-up of hexamethylene diisocyanate-, biphenylmethane diisocyanate-, and toluene diisocyanate-induced asthma. In 1976-1992 245 new cases of asthma induced by diisocyanates were diagnosed, caused by hexamethylene diisocyanate (HDI) in 39%, diphenylmethane diisocyanate (MDI) in 39%, and toluene diisocyanate (TDI) in 17% of the cases. Our aim was to study the clinical outcome of diisocyanate-induced asthma, A questionnaire was sent to the 235 patients alive in 7995, and validated by reexamining clinically 91 of them. The study was carried out on average 10 (3-19) yr after the diagnosis. Of the patients 82% experienced symptoms of asthma, 34% used no medication, and 35% were on regular medication. The patients having displayed immunoglobulin E (IgE) antibodies to isocyanates used less medication (OR 0.273; Cl 0.098, 0.758) and had fewer symptoms of asthma (OR 0.329; Cl 0.124, 0.875) than the IgE-negative ones. They also had a significantly shorter duration of symptoms (p = 0.0025), latency period (p = 0.0249), and duration of exposure (p = 0.0008) than the IgE-negative patients. This did not, however, entirely explain the more favourable outcome of the IgE-positive patients. Patients with HDI-induced asthma used less medication (OR 0.412; Cl 0.229, 0.739) than patients with MDI- and TDI-induced asthma. The results confirm the generally rather poor medical outcome of diisocyanate-induced asthma; the persistence of symptoms and unspecific bronchial reactivity were pronounced in TDI-induced asthma. A more favourable outcome was associated with IgE mediation and HDI inducement.. occupational asthma| natural-history| isocyanates| antibodies| workers| ige| reactivity| diagnosis| challenge| exposure.	AUG-2000	occupational asthma| natural-history| isocyanates| antibodies| workers| ige| reactivity| diagnosis| challenge| exposure	Piirila, PL; Nordman, H; Keskinen, HM; Luukkonen, R; Salo, SP; Tuomi, TO; Tuppurainen, M	Long-term follow-up of hexamethylene diisocyanate-, biphenylmethane diisocyanate-, and toluene diisocyanate-induced asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		OCCUPATIONAL ASTHMA; NATURAL-HISTORY; ISOCYANATES; ANTIBODIES; WORKERS; IGE; REACTIVITY; DIAGNOSIS; CHALLENGE; EXPOSURE	In 1976-1992 245 new cases of asthma induced by diisocyanates were diagnosed, caused by hexamethylene diisocyanate (HDI) in 39%, diphenylmethane diisocyanate (MDI) in 39%, and toluene diisocyanate (TDI) in 17% of the cases. Our aim was to study the clinical outcome of diisocyanate-induced asthma, A questionnaire was sent to the 235 patients alive in 7995, and validated by reexamining clinically 91 of them. The study was carried out on average 10 (3-19) yr after the diagnosis. Of the patients 82% experienced symptoms of asthma, 34% used no medication, and 35% were on regular medication. The patients having displayed immunoglobulin E (IgE) antibodies to isocyanates used less medication (OR 0.273; Cl 0.098, 0.758) and had fewer symptoms of asthma (OR 0.329; Cl 0.124, 0.875) than the IgE-negative ones. They also had a significantly shorter duration of symptoms (p = 0.0025), latency period (p = 0.0249), and duration of exposure (p = 0.0008) than the IgE-negative patients. This did not, however, entirely explain the more favourable outcome of the IgE-positive patients. Patients with HDI-induced asthma used less medication (OR 0.412; Cl 0.229, 0.739) than patients with MDI- and TDI-induced asthma. The results confirm the generally rather poor medical outcome of diisocyanate-induced asthma; the persistence of symptoms and unspecific bronchial reactivity were pronounced in TDI-induced asthma. A more favourable outcome was associated with IgE mediation and HDI inducement.	35	77	2000	7		General & Internal Medicine; Respiratory System
Anaphylaxis after thrombin injection of a femoral pseudoaneurysm: Recommendations for prevention. After the injection treatment of a femoral pseudoaneurysm, an anaphylactic reaction occurred in a patient undergoing hemodialysis who previously had repeated exposure to thrombin. Before injecting bovine thrombin in patients with a history of prior exposure, we recommend that they undergo skin prick testing to detect possible allergy.. topical thrombin| coagulation.	JUL-2000	topical thrombin| coagulation	Pope, M; Johnston, KW	Anaphylaxis after thrombin injection of a femoral pseudoaneurysm: Recommendations for prevention		JOURNAL OF VASCULAR SURGERY		TOPICAL THROMBIN; COAGULATION	After the injection treatment of a femoral pseudoaneurysm, an anaphylactic reaction occurred in a patient undergoing hemodialysis who previously had repeated exposure to thrombin. Before injecting bovine thrombin in patients with a history of prior exposure, we recommend that they undergo skin prick testing to detect possible allergy.	11	77	2000	2	10.1067/mva.2000.106498	Surgery; Cardiovascular System & Cardiology
Enhanced allergic sensitization by residual oil fly ash particles is mediated by soluble metal constituents. Epidemiological studies have demonstrated an association between elevated levels of particulate matter (PM) air pollutants and exacerbation of asthma symptoms. We have shown in a Brown Norway (BN) rat model of house dust mite (HDM) allergy that preexposure to residual oil By ash (ROFA) particles enhanced the sensitization phase such that the secondary immune response and associated lung injury were increased after allergen challenge. To determine whether the metals present in ROFA mediated this effect, BN rats were intratracheally instilled with either ROFA (1000 mu g) or acidified saline + NiSO4 (105.12 mu g), VSO4 (98.2 mu g), FeSO4 (58.49 mu g), or a mixture (Mix) of each metal. HDM-specific IgE was higher in the serum of the ROFA, Ni, V, and Mix groups than in the HDM group after challenge, and antigen-induced bronchoconstriction responses were increased in the Ni group. Lymphocyte proliferation to antigen was increased in the ROFA, Ni, and V groups compared to controls. Total protein and eosinophil peroxidase levels were elevated in the Fe group, and eosinophil numbers in the bronchoalveolar lavage fluid (BALF) were increased in the ROFA and Fe groups compared to HDM control. IL-5 and IL-13 mRNA expression was also increased in the lung tissue of all metal and ROFA-treated groups, while BALF IL-10 was elevated in the Fe and Mix groups, and IL-6 and TNF-alpha were elevated in the metal and ROFA-treated groups compared to controls. These results suggest that ROFA's metallic constituents mediate enhancement of sensitization to HDM and that pulmonary inflammation may play a role in this adjuvant effect. (C) 2000 Academic Press.. particulate matter| metals| adjuvant| asthma| immediate bronchoconstriction| il-5| il-6| il-10| il-13| tnf-alpha| ige| eosinophils|particulate air-pollution| messenger-rna expression| diesel exhaust particles| emergency room visits| house-dust mite| cytokine production| in-vivo| epithelial-cells| ige production| leukocyte adhesion.	MAY 15-2000	particulate matter| metals| adjuvant| asthma| immediate bronchoconstriction| il-5| il-6| il-10| il-13| tnf-alpha| ige| eosinophils|particulate air-pollution| messenger-rna expression| diesel exhaust particles| emergency room visits| house-dust mite| cytokine production| in-vivo| epithelial-cells| ige production| leukocyte adhesion	Lambert, AL; Dong, WM; Selgrade, MJK; Gilmour, MI	Enhanced allergic sensitization by residual oil fly ash particles is mediated by soluble metal constituents		TOXICOLOGY AND APPLIED PHARMACOLOGY	particulate matter; metals; adjuvant; asthma; immediate bronchoconstriction; IL-5; IL-6; IL-10; IL-13; TNF-alpha; IgE; eosinophils	PARTICULATE AIR-POLLUTION; MESSENGER-RNA EXPRESSION; DIESEL EXHAUST PARTICLES; EMERGENCY ROOM VISITS; HOUSE-DUST MITE; CYTOKINE PRODUCTION; IN-VIVO; EPITHELIAL-CELLS; IGE PRODUCTION; LEUKOCYTE ADHESION	Epidemiological studies have demonstrated an association between elevated levels of particulate matter (PM) air pollutants and exacerbation of asthma symptoms. We have shown in a Brown Norway (BN) rat model of house dust mite (HDM) allergy that preexposure to residual oil By ash (ROFA) particles enhanced the sensitization phase such that the secondary immune response and associated lung injury were increased after allergen challenge. To determine whether the metals present in ROFA mediated this effect, BN rats were intratracheally instilled with either ROFA (1000 mu g) or acidified saline + NiSO4 (105.12 mu g), VSO4 (98.2 mu g), FeSO4 (58.49 mu g), or a mixture (Mix) of each metal. HDM-specific IgE was higher in the serum of the ROFA, Ni, V, and Mix groups than in the HDM group after challenge, and antigen-induced bronchoconstriction responses were increased in the Ni group. Lymphocyte proliferation to antigen was increased in the ROFA, Ni, and V groups compared to controls. Total protein and eosinophil peroxidase levels were elevated in the Fe group, and eosinophil numbers in the bronchoalveolar lavage fluid (BALF) were increased in the ROFA and Fe groups compared to HDM control. IL-5 and IL-13 mRNA expression was also increased in the lung tissue of all metal and ROFA-treated groups, while BALF IL-10 was elevated in the Fe and Mix groups, and IL-6 and TNF-alpha were elevated in the metal and ROFA-treated groups compared to controls. These results suggest that ROFA's metallic constituents mediate enhancement of sensitization to HDM and that pulmonary inflammation may play a role in this adjuvant effect. (C) 2000 Academic Press.	63	77	2000	10	10.1006/taap.2000.8932	Pharmacology & Pharmacy; Toxicology
Urbanization and childhood asthma: An African perspective. The increasing prevalence of childhood asthma in the developed world is a cause for concern. Much research is currently being conducted in an attempt to identify possible reasons for this occurrence. A so-called Western lifestyle has been the factor most commonly cited to explain this worrying increase in asthma prevalence. In essence, this implies a way of life where children are exposed from early infancy to a wide range of foods, infections, indoor and outdoor allergens, and irritants and to the effects of motor vehicle pollution, Until fairly recently, children in many African countries lived mainly in rural areas and were not exposed to the effects of a Western lifestyle, Early studies in a limited number of African countries showed a very low rural prevalence of childhood asthma, especially where children lived according to a traditional lifestyle, These same studies showed that asthma was not uncommon in urbanized African children. There has been an increasing tendency over the past 20 years for those in rural communities to move to the large urban centers. More recent childhood asthma prevalence studies, especially those from Kenya and Ghana, have confirmed the urban-rural differences but have shown a much narrower gap. In part this may be the result of exposure of rural children to agricultural pesticides and irritants as well as of an increasing tendency to adopt a more Westernized lifestyle such as the use of beds with mattresses, pillows, and blankets, These circumstances on the African continent provide a natural laboratory in the quest for factors that influence the development of asthma in susceptible children, Once more fully elucidated, it is possible that much valuable information will be available to combat the relentless increase in childhood asthma both here as well as in the developed world.. africa| urbanization| childhood asthma| prevalence| parasites|exercise-induced bronchospasm| kenyan school-children| prevalence| urban| schoolchildren| infection| birth| atopy.	FEB-2000	africa| urbanization| childhood asthma| prevalence| parasites|exercise-induced bronchospasm| kenyan school-children| prevalence| urban| schoolchildren| infection| birth| atopy	Weinberg, EG	Urbanization and childhood asthma: An African perspective		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Africa; urbanization; childhood asthma; prevalence; parasites	EXERCISE-INDUCED BRONCHOSPASM; KENYAN SCHOOL-CHILDREN; PREVALENCE; URBAN; SCHOOLCHILDREN; INFECTION; BIRTH; ATOPY	The increasing prevalence of childhood asthma in the developed world is a cause for concern. Much research is currently being conducted in an attempt to identify possible reasons for this occurrence. A so-called Western lifestyle has been the factor most commonly cited to explain this worrying increase in asthma prevalence. In essence, this implies a way of life where children are exposed from early infancy to a wide range of foods, infections, indoor and outdoor allergens, and irritants and to the effects of motor vehicle pollution, Until fairly recently, children in many African countries lived mainly in rural areas and were not exposed to the effects of a Western lifestyle, Early studies in a limited number of African countries showed a very low rural prevalence of childhood asthma, especially where children lived according to a traditional lifestyle, These same studies showed that asthma was not uncommon in urbanized African children. There has been an increasing tendency over the past 20 years for those in rural communities to move to the large urban centers. More recent childhood asthma prevalence studies, especially those from Kenya and Ghana, have confirmed the urban-rural differences but have shown a much narrower gap. In part this may be the result of exposure of rural children to agricultural pesticides and irritants as well as of an increasing tendency to adopt a more Westernized lifestyle such as the use of beds with mattresses, pillows, and blankets, These circumstances on the African continent provide a natural laboratory in the quest for factors that influence the development of asthma in susceptible children, Once more fully elucidated, it is possible that much valuable information will be available to combat the relentless increase in childhood asthma both here as well as in the developed world.	32	77	2000	8	10.1016/S0091-6749(00)90069-1	Allergy; Immunology
Vitamin D insufficiency is associated with challenge-proven food allergy in infants. Background: Epidemiological evidence has shown that pediatric food allergy is more prevalent in regions further from the equator, suggesting that vitamin D insufficiency may play a role in this disease. Objective: To investigate the role of vitamin D status in infantile food allergy. Methods: A population sample of 5276 one-year-old infants underwent skin prick testing to peanut, egg, sesame, and cow's milk or shrimp. All those with a detectable wheal and a random sample of participants with negative skin prick test results attended a hospital-based food challenge clinic. Blood samples were available for 577 infants (344 with challenge-proven food allergy, 74 sensitized but tolerant to food challenge, 159 negative on skin prick test and food challenge). Serum 25-hydroxyvitamin D levels were measured by using liquid chromatography tandem mass spectrometry. Associations between serum 25-hydroxyvitamin D and food allergy were examined by using multiple logistic regression, adjusting for potential risk and confounding factors. Results: Infants of Australian-born parents, but not of parents born overseas, with vitamin D insufficiency (<= 50 nmol/L) were more likely to be peanut (adjusted odds ratio [aOR], 11.51; 95% CI, 2.01-65.79; P = .006) and/or egg (aOR, 3.79; 95% CI, 1.1912.08; P = .025) allergic than were those with adequate vitamin D levels independent of eczema status. Among those with Australian-born parents, infants with vitamin D insufficiency were more likely to have multiple food allergies (>= 2) rather than a single food allergy (aOR, 10.48; 95% CI, 1.60-68.61 vs aOR, 1.82; 95% CI, 0.38-8.77, respectively). Conclusions: These results provide the first direct evidence that vitamin D sufficiency may be an important protective factor for food allergy in the first year of life. (J Allergy Clin Immunol 2013; 131:1109-16.). vitamin d| food allergy| peanut allergy| egg allergy| population| oral food challenge| eczema| epigenetic|regulatory t-cells| united-states| birth cohort| population| prevalence| children| latitude| radiation| exposure| season.	APR-2013	vitamin d| food allergy| peanut allergy| egg allergy| population| oral food challenge| eczema| epigenetic|regulatory t-cells| united-states| birth cohort| population| prevalence| children| latitude| radiation| exposure| season	Allen, KJ; Koplin, JJ; Ponsonby, AL; Gurrin, LC; Wake, M; Vuillermin, P; Martin, P; Matheson, M; Lowe, A; Robinson, M; Tey, D; Osborne, NJ; Dang, T; Tan, HTT; Thiele, L; Anderson, D; Czech, H; Sanjeevan, J; Zurzolo, G; Dwyer, T; Tang, MLK; Hill, D; Dharmage, SC	Vitamin D insufficiency is associated with challenge-proven food allergy in infants		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Vitamin D; food allergy; peanut allergy; egg allergy; population; oral food challenge; eczema; epigenetic	REGULATORY T-CELLS; UNITED-STATES; BIRTH COHORT; POPULATION; PREVALENCE; CHILDREN; LATITUDE; RADIATION; EXPOSURE; SEASON	Background: Epidemiological evidence has shown that pediatric food allergy is more prevalent in regions further from the equator, suggesting that vitamin D insufficiency may play a role in this disease. Objective: To investigate the role of vitamin D status in infantile food allergy. Methods: A population sample of 5276 one-year-old infants underwent skin prick testing to peanut, egg, sesame, and cow's milk or shrimp. All those with a detectable wheal and a random sample of participants with negative skin prick test results attended a hospital-based food challenge clinic. Blood samples were available for 577 infants (344 with challenge-proven food allergy, 74 sensitized but tolerant to food challenge, 159 negative on skin prick test and food challenge). Serum 25-hydroxyvitamin D levels were measured by using liquid chromatography tandem mass spectrometry. Associations between serum 25-hydroxyvitamin D and food allergy were examined by using multiple logistic regression, adjusting for potential risk and confounding factors. Results: Infants of Australian-born parents, but not of parents born overseas, with vitamin D insufficiency (<= 50 nmol/L) were more likely to be peanut (adjusted odds ratio [aOR], 11.51; 95% CI, 2.01-65.79; P = .006) and/or egg (aOR, 3.79; 95% CI, 1.1912.08; P = .025) allergic than were those with adequate vitamin D levels independent of eczema status. Among those with Australian-born parents, infants with vitamin D insufficiency were more likely to have multiple food allergies (>= 2) rather than a single food allergy (aOR, 10.48; 95% CI, 1.60-68.61 vs aOR, 1.82; 95% CI, 0.38-8.77, respectively). Conclusions: These results provide the first direct evidence that vitamin D sufficiency may be an important protective factor for food allergy in the first year of life. (J Allergy Clin Immunol 2013; 131:1109-16.)	33	76	2013	14	10.1016/j.jaci.2013.01.017	Allergy; Immunology
Thymic stromal lymphopoietin and allergic disease. The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways, and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies in both human subjects and murine models have implicated TSLP in the development and progression of allergic diseases. This review will highlight recent advances in the understanding of the role of TSLP in these inflammatory diseases. Importantly, these insights into TSLP's multifaceted role could potentially allow for novel therapeutic manipulations of these disorders. (J Allergy Clin Immunol 2012; 130:845-52.). thymic stromal lymphopoietin| asthma| allergy| atopic dermatitis| inflammation|obstructive pulmonary-disease| nasal epithelial-cells| retinoid-x-receptor| igm(+) b-cells| cd4(+) t-cells| atopic-dermatitis| dendritic cells| tslp receptor| cutting edge| ox40 ligand.	OCT-2012	thymic stromal lymphopoietin| asthma| allergy| atopic dermatitis| inflammation|obstructive pulmonary-disease| nasal epithelial-cells| retinoid-x-receptor| igm(+) b-cells| cd4(+) t-cells| atopic-dermatitis| dendritic cells| tslp receptor| cutting edge| ox40 ligand	Ziegler, SF	Thymic stromal lymphopoietin and allergic disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Thymic stromal lymphopoietin; asthma; allergy; atopic dermatitis; inflammation	OBSTRUCTIVE PULMONARY-DISEASE; NASAL EPITHELIAL-CELLS; RETINOID-X-RECEPTOR; IGM(+) B-CELLS; CD4(+) T-CELLS; ATOPIC-DERMATITIS; DENDRITIC CELLS; TSLP RECEPTOR; CUTTING EDGE; OX40 LIGAND	The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergen contact first occurs at mucosal sites exposed to the external environment, such as the skin, airways, and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies in both human subjects and murine models have implicated TSLP in the development and progression of allergic diseases. This review will highlight recent advances in the understanding of the role of TSLP in these inflammatory diseases. Importantly, these insights into TSLP's multifaceted role could potentially allow for novel therapeutic manipulations of these disorders. (J Allergy Clin Immunol 2012; 130:845-52.)	92	76	2012	8	10.1016/j.jaci.2012.07.010	Allergy; Immunology
Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children. Rationale: Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. Objectives To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. Methods: A cross-sectional study was conducted of 560 children ages 6-14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Measurements and Main Results Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P = 0.001) and atopy, and a lower FEV1/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P = 0.04) cases. Conclusions Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.. vitamin d| asthma exacerbations| puerto ricans| childhood|genetic ancestry| african ancestry| lung-function| induction| exposure| populations| predictors| admixture| markers| adults.	JUL 15-2012	vitamin d| asthma exacerbations| puerto ricans| childhood|genetic ancestry| african ancestry| lung-function| induction| exposure| populations| predictors| admixture| markers| adults	Brehm, JM; Acosta-Perez, E; Klei, L; Roeder, K; Barmada, M; Boutaoui, N; Forno, E; Kelly, R; Paul, K; Sylvia, J; Litonjua, AA; Cabana, M; Alvarez, M; Colon-Semidey, A; Canino, G; Celedon, JC	Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	vitamin D; asthma exacerbations; Puerto Ricans; childhood	GENETIC ANCESTRY; AFRICAN ANCESTRY; LUNG-FUNCTION; INDUCTION; EXPOSURE; POPULATIONS; PREDICTORS; ADMIXTURE; MARKERS; ADULTS	Rationale: Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans. Objectives To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors. Methods: A cross-sectional study was conducted of 560 children ages 6-14 years with (n = 287) and without (n = 273) asthma in San Juan, Puerto Rico. We measured plasma vitamin D and estimated the percentage of African racial ancestry among participants using genome-wide genotypic data. We tested whether vitamin D insufficiency is associated with severe asthma exacerbations, lung function, or atopy (greater than or equal to one positive IgE to allergens) using logistic or linear regression. Multivariate models were adjusted for African ancestry, time outdoors, atopy, and other covariates. Measurements and Main Results Vitamin D insufficiency was common in children with (44%) and without (47%) asthma. In multivariate analyses, vitamin D insufficiency was associated with higher odds of greater than or equal to one severe asthma exacerbation in the prior year (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.5-4.9; P = 0.001) and atopy, and a lower FEV1/FVC in cases. After stratification by atopy, the magnitude of the association between vitamin D insufficiency and severe exacerbations was greater in nonatopic (OR, 6.2; 95% CI, 2-21.6; P = 0.002) than in atopic (OR, 2; 95% CI, 1-4.1; P = 0.04) cases. Conclusions Vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, or markers of disease severity or control.	38	76	2012	7	10.1164/rccm.201203-0431OC	General & Internal Medicine; Respiratory System
Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection. The molecular mechanisms that drive mucosal T helper type 2 (T(H)2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell-derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T(H)2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T(H)2 responses.. in-vivo| airway hyperreactivity| dendritic cells| acute schistosomiasis| cytokine production| helminth infection| adaptive immunity| effector function| epithelial-cells| t-cells.	MAR 12-2012	in-vivo| airway hyperreactivity| dendritic cells| acute schistosomiasis| cytokine production| helminth infection| adaptive immunity| effector function| epithelial-cells| t-cells	Wills-Karp, M; Rani, R; Dienger, K; Lewkowich, I; Fox, JG; Perkins, C; Lewis, L; Finkelman, FD; Smith, DE; Bryce, PJ; Kurt-Jones, EA; Wang, TC; Sivaprasad, U; Hershey, GK; Herbert, DR	Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection		JOURNAL OF EXPERIMENTAL MEDICINE		IN-VIVO; AIRWAY HYPERREACTIVITY; DENDRITIC CELLS; ACUTE SCHISTOSOMIASIS; CYTOKINE PRODUCTION; HELMINTH INFECTION; ADAPTIVE IMMUNITY; EFFECTOR FUNCTION; EPITHELIAL-CELLS; T-CELLS	The molecular mechanisms that drive mucosal T helper type 2 (T(H)2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell-derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T(H)2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T(H)2 responses.	81	76	2012	16	10.1084/jem.20110079	Immunology; Research & Experimental Medicine
Gut-Tropic T Cells That Express Integrin alpha 4 beta 7 and CCR9 Are Required for Induction of Oral Immune Tolerance in Mice. BACKGROUND & AIMS: Induction of oral immune tolerance (OT) blocks proinflammatory responses to orally administered antigens and might be used to treat autoimmune conditions. We investigated whether gut-tropic T cells that express the integrin alpha 4 beta 7 and the chemokine receptor CCR9 are required for OT. METHODS: Skin delayed-type hypersensitivity and experimental autoimmune encephalomyelitis were used to monitor OT in mice. To assess the role of receptors that mediate localization of lymphocytes to the gut (gut-homing receptors) in induction of OT, we studied CCR9(-/-) and beta 7(-/-) mice and also blocked the alpha 4 beta 7 ligand MAdCAM-1 in wild-type mice. We used DEREG and Scurfy mice to assess the role of Foxp3(+) regulatory T cells (Treg) and IL-10(-/-) and IL-10R beta(-/-) mice to examine the role of interleukin (IL)-10 in induction of OT. RESULTS: OT could not be induced in CCR9(-/-) or beta 7(-/-) mice, or when MAdCAM-1 was blocked in wild-type mice, indicating that gut-homing receptors are required for oral tolerization. Consistent with the role of all-trans retinoic acid in inducing gut-homing T cells, OT could not be induced in mice depleted of vitamin A. OT was rescued in CCR9(-/-) mice following adoptive transfer of wild-type T cells, but not CCR9(-/-) or beta 7(-/-) T cells. Gut-homing T cells are therefore necessary and sufficient to induce OT. Wild-type Treg and IL-10 were required to restore OT to CCR9-/- mice, indicating that homing and functional differentiation of IL-10-producing Treg in the gut is required for OT. Conversely, transfer of CCR9(-/-) or beta 7(-/-) T cells to wild-type mice partially inhibited OT. CONCLUSIONS: Expression of CCR9 and alpha 4 beta 7 on T cells and their subsequent localization to the gut is required for induction of OT in mice. Therapies designed to block gut-homing receptors might, under some conditions, interfere with normal tolerogenic mechanisms in the intestinal mucosa.. immune regulation| autoimmunity| allergy| intestine| peyer's patch|plasmacytoid dendritic cells| retinoic-acid| small-intestine| suppression| colitis| absence| il-10| th17| inflammation| lymphocytes.	DEC-2011	immune regulation| autoimmunity| allergy| intestine| peyer's patch|plasmacytoid dendritic cells| retinoic-acid| small-intestine| suppression| colitis| absence| il-10| th17| inflammation| lymphocytes	Cassani, B; Villablanca, EJ; Quintana, FJ; Love, PE; Lacy-Hulbert, A; Blaner, WS; Sparwasser, T; Snapper, SB; Weiner, HL; Mora, JR	Gut-Tropic T Cells That Express Integrin alpha 4 beta 7 and CCR9 Are Required for Induction of Oral Immune Tolerance in Mice		GASTROENTEROLOGY	Immune Regulation; Autoimmunity; Allergy; Intestine; Peyer's Patch	PLASMACYTOID DENDRITIC CELLS; RETINOIC-ACID; SMALL-INTESTINE; SUPPRESSION; COLITIS; ABSENCE; IL-10; TH17; INFLAMMATION; LYMPHOCYTES	BACKGROUND & AIMS: Induction of oral immune tolerance (OT) blocks proinflammatory responses to orally administered antigens and might be used to treat autoimmune conditions. We investigated whether gut-tropic T cells that express the integrin alpha 4 beta 7 and the chemokine receptor CCR9 are required for OT. METHODS: Skin delayed-type hypersensitivity and experimental autoimmune encephalomyelitis were used to monitor OT in mice. To assess the role of receptors that mediate localization of lymphocytes to the gut (gut-homing receptors) in induction of OT, we studied CCR9(-/-) and beta 7(-/-) mice and also blocked the alpha 4 beta 7 ligand MAdCAM-1 in wild-type mice. We used DEREG and Scurfy mice to assess the role of Foxp3(+) regulatory T cells (Treg) and IL-10(-/-) and IL-10R beta(-/-) mice to examine the role of interleukin (IL)-10 in induction of OT. RESULTS: OT could not be induced in CCR9(-/-) or beta 7(-/-) mice, or when MAdCAM-1 was blocked in wild-type mice, indicating that gut-homing receptors are required for oral tolerization. Consistent with the role of all-trans retinoic acid in inducing gut-homing T cells, OT could not be induced in mice depleted of vitamin A. OT was rescued in CCR9(-/-) mice following adoptive transfer of wild-type T cells, but not CCR9(-/-) or beta 7(-/-) T cells. Gut-homing T cells are therefore necessary and sufficient to induce OT. Wild-type Treg and IL-10 were required to restore OT to CCR9-/- mice, indicating that homing and functional differentiation of IL-10-producing Treg in the gut is required for OT. Conversely, transfer of CCR9(-/-) or beta 7(-/-) T cells to wild-type mice partially inhibited OT. CONCLUSIONS: Expression of CCR9 and alpha 4 beta 7 on T cells and their subsequent localization to the gut is required for induction of OT in mice. Therapies designed to block gut-homing receptors might, under some conditions, interfere with normal tolerogenic mechanisms in the intestinal mucosa.	44	76	2011	10	10.1053/j.gastro.2011.09.015	Gastroenterology & Hepatology
Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens. P>The broad applicability of allergen-specific immunotherapy for the treatment and eventually prevention of IgE-mediated allergy is limited by the poor quality and allergenic activity of natural allergen extracts that are used for the production of current allergy vaccines. Today, the genetic code of the most important allergens has been deciphered; recombinant allergens equalling their natural counterparts have been produced for diagnosis and immunotherapy, and a large panel of genetically modified allergens with reduced allergenic activity has been characterized to improve safety of immunotherapy and explore allergen-specific prevention strategies. Successful immunotherapy studies have been performed with recombinant allergens and hypoallergenic allergen derivatives and will lead to the registration of the first recombinant allergen-based vaccines in the near future. There is no doubt that recombinant allergen-based vaccination strategies will be generally applicable to most allergen sources, including respiratory, food and venom allergens and allow to produce safe allergy vaccines for the treatment of the most common forms of IgE-mediated allergies.. allergy| clinical trial| immunotherapy| recombinant allergen|birch-pollen allergen| bet v 1| dust mite allergen| 3-year double-blind| b-cell epitopes| phl p 1| immunoglobulin-e| ige antibodies| sublingual immunotherapy| diagnostic gatekeepers.	JUN-2011	allergy| clinical trial| immunotherapy| recombinant allergen|birch-pollen allergen| bet v 1| dust mite allergen| 3-year double-blind| b-cell epitopes| phl p 1| immunoglobulin-e| ige antibodies| sublingual immunotherapy| diagnostic gatekeepers	Valenta, R; Linhart, B; Swoboda, I; Niederberger, V	Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens		ALLERGY	allergy; clinical trial; immunotherapy; recombinant allergen	BIRCH-POLLEN ALLERGEN; BET V 1; DUST MITE ALLERGEN; 3-YEAR DOUBLE-BLIND; B-CELL EPITOPES; PHL P 1; IMMUNOGLOBULIN-E; IGE ANTIBODIES; SUBLINGUAL IMMUNOTHERAPY; DIAGNOSTIC GATEKEEPERS	P>The broad applicability of allergen-specific immunotherapy for the treatment and eventually prevention of IgE-mediated allergy is limited by the poor quality and allergenic activity of natural allergen extracts that are used for the production of current allergy vaccines. Today, the genetic code of the most important allergens has been deciphered; recombinant allergens equalling their natural counterparts have been produced for diagnosis and immunotherapy, and a large panel of genetically modified allergens with reduced allergenic activity has been characterized to improve safety of immunotherapy and explore allergen-specific prevention strategies. Successful immunotherapy studies have been performed with recombinant allergens and hypoallergenic allergen derivatives and will lead to the registration of the first recombinant allergen-based vaccines in the near future. There is no doubt that recombinant allergen-based vaccination strategies will be generally applicable to most allergen sources, including respiratory, food and venom allergens and allow to produce safe allergy vaccines for the treatment of the most common forms of IgE-mediated allergies.	89	76	2011	9	10.1111/j.1398-9995.2011.02565.x	Allergy; Immunology
Allergy-related outcomes in relation to serum IgE: Results from the National Health and Nutrition Examination Survey 2005-2006. Background: The National Health and Nutrition Examination Survey (NHANES) 2005-2006 was the first population-based study to investigate levels of serum total and allergen-specific IgE in the general US population. Objective: We estimated the prevalence of allergy-related outcomes and examined relationships between serum IgE levels and these outcomes in a representative sample of the US population. Methods: Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Study subjects aged 6 years and older (n = 8086) had blood taken for measurement of total IgE and 19 specific IgE levels against common aeroallergens, including Alternaria alternata, Aspergillus fumigatus, Bermuda grass, birch, oak, ragweed, Russian thistle, rye grass, cat dander, cockroach, dog dander, dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus), mouse and rat urine proteins, and selected foods (egg white, cow's milk, peanut, and shrimp). Serum samples were analyzed for total and allergen-specific IgE by using the Pharmacia CAP System. Information on allergy-related outcomes and demographics was collected by questionnaire. Results: In NHANES 2005-2006, 6.6% reported current hay fever, and 23.5% had current allergies. Allergy-related outcomes increased with increasing total IgE levels (adjusted odds ratios for a 10-fold increase in total IgE level of 1.86 [95% CI, 1.44-2.41] for hay fever and 1.64 [ 95% CI, 1.41-1.91] for allergies). Increased levels of plant-, pet-, and mold-specific IgE contributed independently to allergy-related symptoms. The greatest increase in odds was observed for hay fever and plant-specific IgE (adjusted odds ratio, 4.75; 95% CI, 3.83-5.88). Conclusion: In the US population self-reported allergy symptoms are most consistently associated with increased levels of plant-, pet-, and mold-specific IgE. (J Allergy Clin Immunol 2011;127:1226-35.). allergen| allergy| allergic sensitization| serum ige|inhalant allergens| natural-history| united-states| risk-factors| dust-mite| skin-test| us homes| rhinitis| prevalence| asthma.	MAY-2011	allergen| allergy| allergic sensitization| serum ige|inhalant allergens| natural-history| united-states| risk-factors| dust-mite| skin-test| us homes| rhinitis| prevalence| asthma	Salo, PM; Calatroni, A; Gergen, PJ; Hoppin, JA; Sever, ML; Jaramillo, R; Arbes, SJ; Zeldin, DC	Allergy-related outcomes in relation to serum IgE: Results from the National Health and Nutrition Examination Survey 2005-2006		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergen; allergy; allergic sensitization; serum IgE	INHALANT ALLERGENS; NATURAL-HISTORY; UNITED-STATES; RISK-FACTORS; DUST-MITE; SKIN-TEST; US HOMES; RHINITIS; PREVALENCE; ASTHMA	Background: The National Health and Nutrition Examination Survey (NHANES) 2005-2006 was the first population-based study to investigate levels of serum total and allergen-specific IgE in the general US population. Objective: We estimated the prevalence of allergy-related outcomes and examined relationships between serum IgE levels and these outcomes in a representative sample of the US population. Methods: Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Study subjects aged 6 years and older (n = 8086) had blood taken for measurement of total IgE and 19 specific IgE levels against common aeroallergens, including Alternaria alternata, Aspergillus fumigatus, Bermuda grass, birch, oak, ragweed, Russian thistle, rye grass, cat dander, cockroach, dog dander, dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus), mouse and rat urine proteins, and selected foods (egg white, cow's milk, peanut, and shrimp). Serum samples were analyzed for total and allergen-specific IgE by using the Pharmacia CAP System. Information on allergy-related outcomes and demographics was collected by questionnaire. Results: In NHANES 2005-2006, 6.6% reported current hay fever, and 23.5% had current allergies. Allergy-related outcomes increased with increasing total IgE levels (adjusted odds ratios for a 10-fold increase in total IgE level of 1.86 [95% CI, 1.44-2.41] for hay fever and 1.64 [ 95% CI, 1.41-1.91] for allergies). Increased levels of plant-, pet-, and mold-specific IgE contributed independently to allergy-related symptoms. The greatest increase in odds was observed for hay fever and plant-specific IgE (adjusted odds ratio, 4.75; 95% CI, 3.83-5.88). Conclusion: In the US population self-reported allergy symptoms are most consistently associated with increased levels of plant-, pet-, and mold-specific IgE. (J Allergy Clin Immunol 2011;127:1226-35.)	48	76	2011	17	10.1016/j.jaci.2010.12.1106	Allergy; Immunology
The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: A large-scale, prospective population-based study. Background: The prevalence and natural history for food protein-induced enterocolitis syndrome (FPIES) have not been determined. Objective: We sought to determine the prevalence, clinical manifestations, and rate of recovery for FPIES in a large-scale, population-based prospective study. Methods: In a prospective study the feeding history of 13,019 infants was obtained. Infants with probable adverse reactions to cow's milk protein (CMP) were clinically examined, skin prick tested, and challenged orally. Diagnostic criteria for CMP-induced FPIES included age less than 9 months, delayed recurrent vomiting (usually with nausea), and lethargy after exposure to CMP in the absence of other IgE-mediated symptoms, such as rash, urticaria, and respiratory symptoms. In addition, a positive challenge response to milk resulted in the above-mentioned gastrointestinal symptoms, removal of milk from the diet resulted in the resolution of those symptoms, or both. Results: Ninety-eight percent of the cohort participated in the study. The cumulative incidence for FPIES was 0.34% (44/13,019 patients). The most common symptoms were recurrent vomiting (100%), lethargy (77%) diarrhea (25%), pallor (14%), and bloody diarrhea (4.5%). All patients had FPIES within the first 6 months of life. By the age of 3 years, 90% of the patients had recovered. We did not detect any concomitant reaction to soy. Eight patients with FPIES had IgE-mediated cow's milk allergy (IgE-CMA). Conclusions: The prevalence of FPIES is significant, and its clinical presentation is distinct from that of IgE-CMA. Most patients with FPIES recover, although a proportion might convert to IgE-CMA. The likelihood for a cross-reactivity to soy in this population was less than previously estimated. (J Allergy Clin Immunol 2011;127:647-53.). food protein-induced enterocolitis syndrome| oral challenge| soy allergy| skin prick test|clinical-features| allergy| challenge| soy.	MAR-2011	food protein-induced enterocolitis syndrome| oral challenge| soy allergy| skin prick test|clinical-features| allergy| challenge| soy	Katz, Y; Goldberg, MR; Rajuan, N; Cohen, A; Leshno, M	The prevalence and natural course of food protein-induced enterocolitis syndrome to cow's milk: A large-scale, prospective population-based study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Food protein-induced enterocolitis syndrome; oral challenge; soy allergy; skin prick test	CLINICAL-FEATURES; ALLERGY; CHALLENGE; SOY	Background: The prevalence and natural history for food protein-induced enterocolitis syndrome (FPIES) have not been determined. Objective: We sought to determine the prevalence, clinical manifestations, and rate of recovery for FPIES in a large-scale, population-based prospective study. Methods: In a prospective study the feeding history of 13,019 infants was obtained. Infants with probable adverse reactions to cow's milk protein (CMP) were clinically examined, skin prick tested, and challenged orally. Diagnostic criteria for CMP-induced FPIES included age less than 9 months, delayed recurrent vomiting (usually with nausea), and lethargy after exposure to CMP in the absence of other IgE-mediated symptoms, such as rash, urticaria, and respiratory symptoms. In addition, a positive challenge response to milk resulted in the above-mentioned gastrointestinal symptoms, removal of milk from the diet resulted in the resolution of those symptoms, or both. Results: Ninety-eight percent of the cohort participated in the study. The cumulative incidence for FPIES was 0.34% (44/13,019 patients). The most common symptoms were recurrent vomiting (100%), lethargy (77%) diarrhea (25%), pallor (14%), and bloody diarrhea (4.5%). All patients had FPIES within the first 6 months of life. By the age of 3 years, 90% of the patients had recovered. We did not detect any concomitant reaction to soy. Eight patients with FPIES had IgE-mediated cow's milk allergy (IgE-CMA). Conclusions: The prevalence of FPIES is significant, and its clinical presentation is distinct from that of IgE-CMA. Most patients with FPIES recover, although a proportion might convert to IgE-CMA. The likelihood for a cross-reactivity to soy in this population was less than previously estimated. (J Allergy Clin Immunol 2011;127:647-53.)	14	76	2011	10	10.1016/j.jaci.2010.12.1105	Allergy; Immunology
"Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children. Many studies have reported that antibiotic use may be associated with increased risk of childhood asthma. Respiratory tract infections in small children may be difficult to distinguish from early symptoms of asthma, and studies may have been confounded by ""protopathic"" bias, where antibiotics are used to treat early symptoms of asthma. These analyses of a cohort including 1,401 US children assess the association between antibiotic use within the first 6 months of life and asthma and allergy at 6 years of age between 2003 and 2007. Antibiotic exposure was associated with increased risk of asthma (adjusted odds ratio = 1.52, 95% confidence interval (CI): 1.07, 2.16). The odds ratio if asthma was first diagnosed after 3 years of age was 1.66 (95% CI: 0.99, 2.79) and, in children with no history of lower respiratory infection in the first year of life, the odds ratio was 1.66 (95% CI: 1.12, 3.46). The adverse effect of antibiotics was particularly strong in children with no family history of asthma (odds ratio = 1.89, 95% CI: 1.00, 3.58) (P(interaction) = 0.03). The odds ratio for a positive allergy blood or skin test was 1.59 (95% CI: 1.10, 2.28). The results show that early antibiotic use was associated with asthma and allergy at 6 years of age, and that protopathic bias was unlikely to account for the main findings.. anti-bacterial agents| asthma| child| cohort studies| hypersensitivity|early-childhood| hygiene hypothesis| 1st year| medication use| increased risk| birth cohort| school-age| early-life| t-cells| infections."	FEB 1-2011	anti-bacterial agents| asthma| child| cohort studies| hypersensitivity|early-childhood| hygiene hypothesis| 1st year| medication use| increased risk| birth cohort| school-age| early-life| t-cells| infections	Risnes, KR; Belanger, K; Murk, W; Bracken, MB	Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children		AMERICAN JOURNAL OF EPIDEMIOLOGY	anti-bacterial agents; asthma; child; cohort studies; hypersensitivity	EARLY-CHILDHOOD; HYGIENE HYPOTHESIS; 1ST YEAR; MEDICATION USE; INCREASED RISK; BIRTH COHORT; SCHOOL-AGE; EARLY-LIFE; T-CELLS; INFECTIONS	"Many studies have reported that antibiotic use may be associated with increased risk of childhood asthma. Respiratory tract infections in small children may be difficult to distinguish from early symptoms of asthma, and studies may have been confounded by ""protopathic"" bias, where antibiotics are used to treat early symptoms of asthma. These analyses of a cohort including 1,401 US children assess the association between antibiotic use within the first 6 months of life and asthma and allergy at 6 years of age between 2003 and 2007. Antibiotic exposure was associated with increased risk of asthma (adjusted odds ratio = 1.52, 95% confidence interval (CI): 1.07, 2.16). The odds ratio if asthma was first diagnosed after 3 years of age was 1.66 (95% CI: 0.99, 2.79) and, in children with no history of lower respiratory infection in the first year of life, the odds ratio was 1.66 (95% CI: 1.12, 3.46). The adverse effect of antibiotics was particularly strong in children with no family history of asthma (odds ratio = 1.89, 95% CI: 1.00, 3.58) (P(interaction) = 0.03). The odds ratio for a positive allergy blood or skin test was 1.59 (95% CI: 1.10, 2.28). The results show that early antibiotic use was associated with asthma and allergy at 6 years of age, and that protopathic bias was unlikely to account for the main findings."	47	76	2011	9	10.1093/aje/kwq400	Public, Environmental & Occupational Health
Sublingual immunotherapy for allergic rhinitis. Background This is an update of a Cochrane Review first published in The Cochrane Library in Issue 2, 2003. Allergic rhinitis is a common condition which can significantly impair quality of life. Immunotherapy by injection can significantly reduce symptoms and medication use but its use is limited by the possibility of severe systemic adverse reactions. Immunotherapy by the sublingual route is therefore of considerable interest. Objectives To evaluate the efficacy and safety of sublingual immunotherapy for allergic rhinitis in adults and children. Search strategy We searched the Cochrane ENT Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; mRCT and additional sources for published and unpublished trials. The date of the most recent search was 14 August 2009. Selection criteria Randomised, double-blind, placebo-controlled trials of sublingual immunotherapy in adults or children. Primary outcome measures were symptom and medication scores. We also collected adverse event data. Data collection and analysis Two independent authors selected studies and assessed risk of bias. One author extracted data which was rechecked by two other authors. We used the standardised mean difference (SMD) with a random-effects model to combine data. Main results We included a total of 60 randomised controlled trials in the review. Forty-nine were suitable for pooling in meta-analyses (2333 SLIT, 2256 placebo participants). Overall, we found a significant reduction in symptoms (SMD-0.49; 95% confidence interval (CI) -0.64 to -0.34, P < 0.00001) andmedication requirements (SMD -0.32; 95% CI -0.43 to -0.21, P < 0.00001) in participants receiving sublingual immunotherapy compared to placebo. None of the trials included in this review reported severe systemic reactions or anaphylaxis, and none of the systemic reactions reported required the use of adrenaline. Authors' conclusions This updated review reinforces the conclusion of the original 2003 Cochrane Review that sublingual immunotherapy is effective for allergic rhinitis and has been proven to be a safe route of administration.. administration, sublingual| allergens [administration & dosage]| desensitization, immunologic [methods]| randomized controlled trials as topic| rhinitis, allergic, perennial [therapy]| rhinitis, allergic, seasonal [therapy]| humans|placebo-controlled trial| double-blind placebo| randomized controlled-trial| grass-pollen immunotherapy| house-dust-mite| standardized 5-grass-pollen extract| parietaria-judaica extract| swallow immunotherapy| clinical-efficacy| birch pollen.	2010	administration, sublingual| allergens [administration & dosage]| desensitization, immunologic [methods]| randomized controlled trials as topic| rhinitis, allergic, perennial [therapy]| rhinitis, allergic, seasonal [therapy]| humans|placebo-controlled trial| double-blind placebo| randomized controlled-trial| grass-pollen immunotherapy| house-dust-mite| standardized 5-grass-pollen extract| parietaria-judaica extract| swallow immunotherapy| clinical-efficacy| birch pollen	Radulovic, S; Calderon, MA; Wilson, D; Durham, S	Sublingual immunotherapy for allergic rhinitis		COCHRANE DATABASE OF SYSTEMATIC REVIEWS	Administration, Sublingual; Allergens [administration & dosage]; Desensitization, Immunologic [methods]; Randomized Controlled Trials as Topic; Rhinitis, Allergic, Perennial [therapy]; Rhinitis, Allergic, Seasonal [therapy]; Humans	PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND PLACEBO; RANDOMIZED CONTROLLED-TRIAL; GRASS-POLLEN IMMUNOTHERAPY; HOUSE-DUST-MITE; STANDARDIZED 5-GRASS-POLLEN EXTRACT; PARIETARIA-JUDAICA EXTRACT; SWALLOW IMMUNOTHERAPY; CLINICAL-EFFICACY; BIRCH POLLEN	Background This is an update of a Cochrane Review first published in The Cochrane Library in Issue 2, 2003. Allergic rhinitis is a common condition which can significantly impair quality of life. Immunotherapy by injection can significantly reduce symptoms and medication use but its use is limited by the possibility of severe systemic adverse reactions. Immunotherapy by the sublingual route is therefore of considerable interest. Objectives To evaluate the efficacy and safety of sublingual immunotherapy for allergic rhinitis in adults and children. Search strategy We searched the Cochrane ENT Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; mRCT and additional sources for published and unpublished trials. The date of the most recent search was 14 August 2009. Selection criteria Randomised, double-blind, placebo-controlled trials of sublingual immunotherapy in adults or children. Primary outcome measures were symptom and medication scores. We also collected adverse event data. Data collection and analysis Two independent authors selected studies and assessed risk of bias. One author extracted data which was rechecked by two other authors. We used the standardised mean difference (SMD) with a random-effects model to combine data. Main results We included a total of 60 randomised controlled trials in the review. Forty-nine were suitable for pooling in meta-analyses (2333 SLIT, 2256 placebo participants). Overall, we found a significant reduction in symptoms (SMD-0.49; 95% confidence interval (CI) -0.64 to -0.34, P < 0.00001) andmedication requirements (SMD -0.32; 95% CI -0.43 to -0.21, P < 0.00001) in participants receiving sublingual immunotherapy compared to placebo. None of the trials included in this review reported severe systemic reactions or anaphylaxis, and none of the systemic reactions reported required the use of adrenaline. Authors' conclusions This updated review reinforces the conclusion of the original 2003 Cochrane Review that sublingual immunotherapy is effective for allergic rhinitis and has been proven to be a safe route of administration.	125	76	2010	135	10.1002/14651858.CD002893.pub2	General & Internal Medicine
Analyses of associations with asthma in four asthma population samples from Canada and Australia. Asthma, atopy, and related phenotypes are heterogeneous complex traits, with both genetic and environmental risk factors. Extensive research has been conducted and over hundred genes have been associated with asthma and atopy phenotypes, but many of these findings have failed to replicate in subsequent studies. To separate true associations from false positives, candidate genes need to be examined in large well-characterized samples, using standardized designs (genotyping, phenotyping and analysis). In an attempt to replicate previous associations we amalgamated the power and resources of four studies and genotyped 5,565 individuals to conduct a genetic association study of 93 previously associated candidate genes for asthma and related phenotypes using the same set of 861 single-nucleotide polymorphisms (SNPs), a common genotyping platform, and relatively harmonized phenotypes. We tested for association between SNPs and the dichotomous outcomes of asthma, atopy, atopic asthma, and airway hyperresponsiveness using a general allelic likelihood ratio test. No SNP in any gene reached significance levels that survived correction for all tested SNPs, phenotypes, and genes. Even after relaxing the usual stringent multiple testing corrections by performing a gene-based analysis (one gene at a time as if no other genes were typed) and by stratifying SNPs based on their prior evidence of association, no genes gave strong evidence of replication. There was weak evidence to implicate the following: IL13, IFNGR2, EDN1, and VDR in asthma; IL18, TBXA2R, IFNGR2, and VDR in atopy; TLR9, TBXA2R, VDR, NOD2, and STAT6 in airway hyperresponsiveness; TLR10, IFNGR2, STAT6, VDR, and NPSR1 in atopic asthma. Additionally we found an excess of SNPs with small effect sizes (OR < 1.4). The low rate of replication may be due to small effect size, differences in phenotypic definition, differential environmental effects, and/or genetic heterogeneity. To aid in future replication studies of asthma genes a comprehensive database was compiled and is available to the scientific community at http://genapha.icapture.ubc.ca.. tobacco-smoke exposure| allergic disorders| primary prevention| childhood asthma| genetic-variants| lung-function| ormdl3 expression| early-life| high-risk| in-utero.	MAY-2009	tobacco-smoke exposure| allergic disorders| primary prevention| childhood asthma| genetic-variants| lung-function| ormdl3 expression| early-life| high-risk| in-utero	Daley, D; Lemire, M; Akhabir, L; Chan-Yeung, M; He, JQ; McDonald, T; Sandford, A; Stefanowicz, D; Tripp, B; Zamar, D; Bosse, Y; Ferretti, V; Montpetit, A; Tessier, MC; Becker, A; Kozyrskyj, AL; Beilby, J; McCaskie, PA; Musk, B; Warrington, N; James, A; Laprise, C; Palmer, LJ; Pare, PD; Hudson, TJ	Analyses of associations with asthma in four asthma population samples from Canada and Australia		HUMAN GENETICS		TOBACCO-SMOKE EXPOSURE; ALLERGIC DISORDERS; PRIMARY PREVENTION; CHILDHOOD ASTHMA; GENETIC-VARIANTS; LUNG-FUNCTION; ORMDL3 EXPRESSION; EARLY-LIFE; HIGH-RISK; IN-UTERO	Asthma, atopy, and related phenotypes are heterogeneous complex traits, with both genetic and environmental risk factors. Extensive research has been conducted and over hundred genes have been associated with asthma and atopy phenotypes, but many of these findings have failed to replicate in subsequent studies. To separate true associations from false positives, candidate genes need to be examined in large well-characterized samples, using standardized designs (genotyping, phenotyping and analysis). In an attempt to replicate previous associations we amalgamated the power and resources of four studies and genotyped 5,565 individuals to conduct a genetic association study of 93 previously associated candidate genes for asthma and related phenotypes using the same set of 861 single-nucleotide polymorphisms (SNPs), a common genotyping platform, and relatively harmonized phenotypes. We tested for association between SNPs and the dichotomous outcomes of asthma, atopy, atopic asthma, and airway hyperresponsiveness using a general allelic likelihood ratio test. No SNP in any gene reached significance levels that survived correction for all tested SNPs, phenotypes, and genes. Even after relaxing the usual stringent multiple testing corrections by performing a gene-based analysis (one gene at a time as if no other genes were typed) and by stratifying SNPs based on their prior evidence of association, no genes gave strong evidence of replication. There was weak evidence to implicate the following: IL13, IFNGR2, EDN1, and VDR in asthma; IL18, TBXA2R, IFNGR2, and VDR in atopy; TLR9, TBXA2R, VDR, NOD2, and STAT6 in airway hyperresponsiveness; TLR10, IFNGR2, STAT6, VDR, and NPSR1 in atopic asthma. Additionally we found an excess of SNPs with small effect sizes (OR < 1.4). The low rate of replication may be due to small effect size, differences in phenotypic definition, differential environmental effects, and/or genetic heterogeneity. To aid in future replication studies of asthma genes a comprehensive database was compiled and is available to the scientific community at http://genapha.icapture.ubc.ca.	50	76	2009	15	10.1007/s00439-009-0643-8	Genetics & Heredity
Early infection with Trichuris trichiura and allergen skin test reactivity in later childhood. Background Allergic diseases cause a large and increasing burden in developed countries and in urban centres in middle-income countries. The causes of this increase are unknown and, currently, there are no interventions to prevent the development of allergic diseases. The 'hygiene hypothesis' has tried to explain the increase through a reduction in the frequency of childhood infections causing a failure to program the immune system for adequate immune regulation. Intestinal helminth parasites are prevalent in childhood in developing countries and are associated with a lower prevalence of allergen skin test reactivity and asthma. Objectives To investigate whether children who had intestinal helminth infections during early childhood have a lower prevalence of allergen skin test reactivity later in childhood. Methods We re-visited a population of 1055 children from whom stool samples had been collected for detection of intestinal helminth infections for another study, and collected new stool samples and performed allergen skin prick testing. Information on potential confounding variables was collected. Results Children with heavy infections with Trichuris trichiura in early childhood had a significantly reduced prevalence of allergen skin test reactivity in later childhood, even in the absence of T. trichiura infection at the time of skin testing in later childhood. Conclusion Early heavy infections with T. trichiura may protect against the development of allergen skin test reactivity in later childhood. Novel treatments to program immune-regulation in early childhood in a way that mimics the effects of early infections with T. trichiura may offer new strategies for the prevention of allergic disease.. allergen skin test reactivity| asthma| atopy| immune programming| intestinal helminths| rhinitis| trichuris trichiura|school-age-children| geohelminth infections| gabonese schoolchildren| helminthic infection| hygiene hypothesis| atopy| parasites| asthma| prevalence| exposure.	NOV-2008	allergen skin test reactivity| asthma| atopy| immune programming| intestinal helminths| rhinitis| trichuris trichiura|school-age-children| geohelminth infections| gabonese schoolchildren| helminthic infection| hygiene hypothesis| atopy| parasites| asthma| prevalence| exposure	Rodrigues, LC; Newcombe, PJ; Cunha, SS; Alcantara-Neves, NM; Genser, B; Cruz, AA; Simoes, SM; Fiaccone, R; Amorim, L; Cooper, PJ; Barreto, ML	Early infection with Trichuris trichiura and allergen skin test reactivity in later childhood		CLINICAL AND EXPERIMENTAL ALLERGY	allergen skin test reactivity; asthma; atopy; immune programming; intestinal helminths; rhinitis; Trichuris trichiura	SCHOOL-AGE-CHILDREN; GEOHELMINTH INFECTIONS; GABONESE SCHOOLCHILDREN; HELMINTHIC INFECTION; HYGIENE HYPOTHESIS; ATOPY; PARASITES; ASTHMA; PREVALENCE; EXPOSURE	Background Allergic diseases cause a large and increasing burden in developed countries and in urban centres in middle-income countries. The causes of this increase are unknown and, currently, there are no interventions to prevent the development of allergic diseases. The 'hygiene hypothesis' has tried to explain the increase through a reduction in the frequency of childhood infections causing a failure to program the immune system for adequate immune regulation. Intestinal helminth parasites are prevalent in childhood in developing countries and are associated with a lower prevalence of allergen skin test reactivity and asthma. Objectives To investigate whether children who had intestinal helminth infections during early childhood have a lower prevalence of allergen skin test reactivity later in childhood. Methods We re-visited a population of 1055 children from whom stool samples had been collected for detection of intestinal helminth infections for another study, and collected new stool samples and performed allergen skin prick testing. Information on potential confounding variables was collected. Results Children with heavy infections with Trichuris trichiura in early childhood had a significantly reduced prevalence of allergen skin test reactivity in later childhood, even in the absence of T. trichiura infection at the time of skin testing in later childhood. Conclusion Early heavy infections with T. trichiura may protect against the development of allergen skin test reactivity in later childhood. Novel treatments to program immune-regulation in early childhood in a way that mimics the effects of early infections with T. trichiura may offer new strategies for the prevention of allergic disease.	35	76	2008	9	10.1111/j.1365-2222.2008.03027.x	Allergy; Immunology
Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA(2)LEN). The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.. aria| asthma| ga(2)len| ige| pharmacotherapy| rhinitis|aqueous nasal spray| placebo-controlled trial| quality-of-life| loratadine 10 mg| intranasal fluticasone propionate| environmental exposure unit| randomized controlled-trial| ebastine 20 mg| leukotriene receptor antagonists| adrenal axis function.	SEP-2006	aria| asthma| ga(2)len| ige| pharmacotherapy| rhinitis|aqueous nasal spray| placebo-controlled trial| quality-of-life| loratadine 10 mg| intranasal fluticasone propionate| environmental exposure unit| randomized controlled-trial| ebastine 20 mg| leukotriene receptor antagonists| adrenal axis function	Bousquet, J; van Cauwenberge, P; Khaled, NA; Bachert, C; Baena-Cagnani, CE; Bouchard, J; Bunnag, C; Canonica, GW; Carlsen, KH; Chen, YZ; Cruz, AA; Custovic, A; Demoly, P; Dubakiene, R; Durham, S; Fokkens, W; Howarth, P; Kemp, J; Kowalski, ML; Kvedariene, V; Lipworth, B; Lockey, R; Lund, V; Mavale-Manuel, S; Meltzer, EO; Mullol, J; Naclerio, R; Nekam, K; Ohta, K; Papadopoulos, N; Passalacqua, G; Pawankar, R; Popov, T; Potter, P; Price, D; Scadding, G; Simons, FER; Spicak, V; Valovirta, E; Wang, DY; Yawn, B; Yusuf, O	Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA(2)LEN)		ALLERGY	ARIA; asthma; GA(2)LEN; IgE; pharmacotherapy; rhinitis	AQUEOUS NASAL SPRAY; PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; LORATADINE 10 MG; INTRANASAL FLUTICASONE PROPIONATE; ENVIRONMENTAL EXPOSURE UNIT; RANDOMIZED CONTROLLED-TRIAL; EBASTINE 20 MG; LEUKOTRIENE RECEPTOR ANTAGONISTS; ADRENAL AXIS FUNCTION	The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.	134	76	2006	11	10.1111/j.1398-9995.2006.01144.x	Allergy; Immunology
Nitric oxide and reactive nitrogen species in airway epithelial signaling and inflammation. Nitric oxide (NO center dot) is produced by many diverse cell types as a cellular or intracellular signaling molecule, by the activation of nitric oxide synthases (NOSs). All three known NOS isoforms are expressed within the respiratory tract and mediate various air-way functional properties such as airway smooth muscle tone, ciliary function, epithelial electrolyte transport, and innate host defense. The respiratory epithelium is a major source of NO center dot in which it regulates normal epithelial cell function and signaling as well as signaling pathways involved in airway inflammation. In addition to its normal physiological properties, increased airway NO center dot production in inflammatory respiratory tract diseases such as asthma may activate additional signaling mechanisms to regulate inflammatory-immune pathways, and epithelial barrier (dys)function or repair. The biological actions of NO center dot are controlled at various levels, including mechanisms that regulate NOS localization and activation, and variable oxidative metabolism of NO center dot resulting in generation of bioactive reactive nitrogen species (RNS). Moreover, in addition to altered production of NO center dot or RNS, the presence of various target enzymes and/or metabolic regulators of NO center dot/RNS can be dramatically altered during airway inflammatory conditions, and contribute to alterations in W-mediated signaling pathways in disease. This review summarizes current knowledge regarding NO center dot-mediated epithelial signaling, as well as disease-related changes in airway NOS biology and target enzymes that affect NO center dot/RNS signaling mechanisms. A detailed understanding of these various changes and their impact on NO center dot signaling pathways are needed to fully appreciate the contributions of NO center dot/RNS to airway inflammation and to develop suitable therapeutic approaches based on regulating NO center dot function. (c) 2006 Elsevier Inc. All rights reserved.. guanylyl cyclase| cgmp| s-nitrosylation| nf-kappa b| asthma|nf-kappa-b| soluble guanylyl cyclase| protein-tyrosine nitration| ciliary beat frequency| s-nitrosylation| cystic-fibrosis| gene-expression| matrix metalloproteinases| cyclooxygenase-2 expression| differential sensitivity.	AUG 15-2006	guanylyl cyclase| cgmp| s-nitrosylation| nf-kappa b| asthma|nf-kappa-b| soluble guanylyl cyclase| protein-tyrosine nitration| ciliary beat frequency| s-nitrosylation| cystic-fibrosis| gene-expression| matrix metalloproteinases| cyclooxygenase-2 expression| differential sensitivity	Bove, PF; van der Vliet, A	Nitric oxide and reactive nitrogen species in airway epithelial signaling and inflammation		FREE RADICAL BIOLOGY AND MEDICINE	guanylyl cyclase; cGMP; S-nitrosylation; NF-kappa B; asthma	NF-KAPPA-B; SOLUBLE GUANYLYL CYCLASE; PROTEIN-TYROSINE NITRATION; CILIARY BEAT FREQUENCY; S-NITROSYLATION; CYSTIC-FIBROSIS; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; CYCLOOXYGENASE-2 EXPRESSION; DIFFERENTIAL SENSITIVITY	Nitric oxide (NO center dot) is produced by many diverse cell types as a cellular or intracellular signaling molecule, by the activation of nitric oxide synthases (NOSs). All three known NOS isoforms are expressed within the respiratory tract and mediate various air-way functional properties such as airway smooth muscle tone, ciliary function, epithelial electrolyte transport, and innate host defense. The respiratory epithelium is a major source of NO center dot in which it regulates normal epithelial cell function and signaling as well as signaling pathways involved in airway inflammation. In addition to its normal physiological properties, increased airway NO center dot production in inflammatory respiratory tract diseases such as asthma may activate additional signaling mechanisms to regulate inflammatory-immune pathways, and epithelial barrier (dys)function or repair. The biological actions of NO center dot are controlled at various levels, including mechanisms that regulate NOS localization and activation, and variable oxidative metabolism of NO center dot resulting in generation of bioactive reactive nitrogen species (RNS). Moreover, in addition to altered production of NO center dot or RNS, the presence of various target enzymes and/or metabolic regulators of NO center dot/RNS can be dramatically altered during airway inflammatory conditions, and contribute to alterations in W-mediated signaling pathways in disease. This review summarizes current knowledge regarding NO center dot-mediated epithelial signaling, as well as disease-related changes in airway NOS biology and target enzymes that affect NO center dot/RNS signaling mechanisms. A detailed understanding of these various changes and their impact on NO center dot signaling pathways are needed to fully appreciate the contributions of NO center dot/RNS to airway inflammation and to develop suitable therapeutic approaches based on regulating NO center dot function. (c) 2006 Elsevier Inc. All rights reserved.	147	76	2006	13	10.1016/j.freeradbiomed.2006.05.011	Biochemistry & Molecular Biology; Endocrinology & Metabolism
Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide-induced inflammatory responses in murine macrophages. Licorice, the roots of Glycyrrhiza inflata, is used by practitioners of alternative medicine to treat individuals with gastric or duodenal ulcers, bronchitis, cough, arthritis, adrenal insufficiency, and allergies. We investigated the anti-inflammatory properties of 4 licorice extracts: extracts of roasted licorice obtained by ethanol (rLE) or water extraction (rLW) and extracts of raw licorice obtained by ethanol (LE) or water extraction (LW). rLE demonstrated strong anti-inflammatory activity through its ability to reduce nitric oxide and prostaglandin E-2 production in the LPS-stimulated mouse macrophage cell, RAW264.7. It also inhibited the production of pro-inflammatory cytokines and CD14 expression on the LPS-stimulated RAW264.7 cells. Further study indicated that LPS-induced degradation and phosphorylation of I kappa-B alpha, along with DNA-binding of NF-kappa B, was significantly inhibited by rLE exposure in RAW264.7 cells. In the murine model, we found that in vivo exposure to rLE-induced an increase in the survival rate, reduced plasma levels of TNF-alpha and IL-6, and increased IL-10 production in LPS-treated mice. Collectively, these data suggest that the use of rLE may be a useful therapeutic approach to various inflammatory diseases. (c) 2006 Elsevier Inc. All rights reserved.. licorice| inflammation| inducible nitric oxide synthase| prostaglandin e-2| nuclear factor-kappa b| pro-inflammatory cytokines|nf-kappa-b| immune-system| isoliquiritigenin| expression| colitis| cells| mice| activation| resolution| mediators.	JUL 7-2006	licorice| inflammation| inducible nitric oxide synthase| prostaglandin e-2| nuclear factor-kappa b| pro-inflammatory cytokines|nf-kappa-b| immune-system| isoliquiritigenin| expression| colitis| cells| mice| activation| resolution| mediators	Kim, JK; Oh, SM; Kwon, HS; Oh, YS; Lim, SS; Shin, HK	Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide-induced inflammatory responses in murine macrophages		BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS	licorice; inflammation; inducible nitric oxide synthase; prostaglandin E-2; nuclear factor-kappa B; pro-inflammatory cytokines	NF-KAPPA-B; IMMUNE-SYSTEM; ISOLIQUIRITIGENIN; EXPRESSION; COLITIS; CELLS; MICE; ACTIVATION; RESOLUTION; MEDIATORS	Licorice, the roots of Glycyrrhiza inflata, is used by practitioners of alternative medicine to treat individuals with gastric or duodenal ulcers, bronchitis, cough, arthritis, adrenal insufficiency, and allergies. We investigated the anti-inflammatory properties of 4 licorice extracts: extracts of roasted licorice obtained by ethanol (rLE) or water extraction (rLW) and extracts of raw licorice obtained by ethanol (LE) or water extraction (LW). rLE demonstrated strong anti-inflammatory activity through its ability to reduce nitric oxide and prostaglandin E-2 production in the LPS-stimulated mouse macrophage cell, RAW264.7. It also inhibited the production of pro-inflammatory cytokines and CD14 expression on the LPS-stimulated RAW264.7 cells. Further study indicated that LPS-induced degradation and phosphorylation of I kappa-B alpha, along with DNA-binding of NF-kappa B, was significantly inhibited by rLE exposure in RAW264.7 cells. In the murine model, we found that in vivo exposure to rLE-induced an increase in the survival rate, reduced plasma levels of TNF-alpha and IL-6, and increased IL-10 production in LPS-treated mice. Collectively, these data suggest that the use of rLE may be a useful therapeutic approach to various inflammatory diseases. (c) 2006 Elsevier Inc. All rights reserved.	47	76	2006	9	10.1016/j.bbrc.2006.05.035	Biochemistry & Molecular Biology; Biophysics
Quality of life and depression in a population of occupational hand eczema patients. Occupational hand eczema (OHE) is the most frequently recognized occupational disease in Denmark, and despite governmental attempts to reduce exposure to harmful occupational allergens, the number of new cases has remained almost unchanged since the mid-1990s. Some studies have indicated that OHE has considerable impact on quality of life (QoL) and may lead to depression. The aims of the study were to determine risk factors for low QoL, the frequency and severity of depression among OHE patients and changes in QoL and depression after 12 months of follow up. The study population, 758 patients, comprised all new recognized cases from the Danish National Board of Industrial Injuries Registry between October 2001 and November 2002. All patients received a questionnaire to determine impairment of QoL and depressive symptoms. A similar follow-up questionnaire was posted after 1 year. The response rate was 82% at baseline and 91% at follow up. The mean Dermatology Life Quality Index total score was 5.5 for all patients and 7.8 for severe OHE cases. Severe OHE cases and lower socioeconomic status were independently associated with low QoL. The prevalence of moderate-to-severe depression was 9%. Only minor changes in QoL and depressive symptoms were found after 12 months of follow up.. health-related quality of life| occupational skin disease| psychosocial factors| socioeconomic status|contact-dermatitis| skin-disease| index dlqi| outpatients| severity| workers| impact.	FEB-2006	health-related quality of life| occupational skin disease| psychosocial factors| socioeconomic status|contact-dermatitis| skin-disease| index dlqi| outpatients| severity| workers| impact	Cvetkovski, RS; Zachariae, R; Jensen, H; Olsen, J; Johansen, JD; Agner, T	Quality of life and depression in a population of occupational hand eczema patients		CONTACT DERMATITIS	health-related quality of life; occupational skin disease; psychosocial factors; socioeconomic status	CONTACT-DERMATITIS; SKIN-DISEASE; INDEX DLQI; OUTPATIENTS; SEVERITY; WORKERS; IMPACT	Occupational hand eczema (OHE) is the most frequently recognized occupational disease in Denmark, and despite governmental attempts to reduce exposure to harmful occupational allergens, the number of new cases has remained almost unchanged since the mid-1990s. Some studies have indicated that OHE has considerable impact on quality of life (QoL) and may lead to depression. The aims of the study were to determine risk factors for low QoL, the frequency and severity of depression among OHE patients and changes in QoL and depression after 12 months of follow up. The study population, 758 patients, comprised all new recognized cases from the Danish National Board of Industrial Injuries Registry between October 2001 and November 2002. All patients received a questionnaire to determine impairment of QoL and depressive symptoms. A similar follow-up questionnaire was posted after 1 year. The response rate was 82% at baseline and 91% at follow up. The mean Dermatology Life Quality Index total score was 5.5 for all patients and 7.8 for severe OHE cases. Severe OHE cases and lower socioeconomic status were independently associated with low QoL. The prevalence of moderate-to-severe depression was 9%. Only minor changes in QoL and depressive symptoms were found after 12 months of follow up.	32	76	2006	6	10.1111/j.0105-1873.2006.00783.x	Allergy; Dermatology
Safety of sublingual-swallow immunotherapy in children aged 3 to 7 years. Background: The minimum age to start specific immunotherapy with inhalant allergens in children has not been clearly established, and position papers discourage its use in children younger than 5 years. Objective: To assess the safety of high-dose sublingual-swallow immunotherapy (SLIT) in a group of children younger than 5 years. Methods: Sixty-five children (51 boys and 14 girls; age range, 38-80 months; mean +/- SD age, 60 +/- 10 years; median age, 60 months) were included in this observational study. They were treated with SLIT with a build-up phase of 11 days, culminating in a top dose of 300 IR (index of reactivity) and a maintenance phase of 300 IR 3 times a week. The allergens used were house dust mites in 42 patients, grass pollen in 11 patients, olive pollen in 5 patients, Parietaria pollen in 4 patients, and cypress pollen in 3 patients. All adverse reactions and changes in the treatment schedule were compared in 2 subgroups: children 38 to 60 months old and children 61 to 80 months old. Results: The average cumulative dose of SLIT was 36,900 IR. Adverse reactions were observed in 11 children, none of them severe enough to require discontinuation of immunotherapy. Six reactions occurred in the 60 months or younger age group and 7 in the older than 60 months age group, with no differences between these 2 groups. Conclusion: High-dose immunotherapy in children younger than 5 years does not cause more adverse reactions than in children aged 5 to 7 years. There is no reason to forbear studies on safety and efficacy of these preparations in young children.. house-dust-mite| double-blind| allergen immunotherapy| therapeutic vaccines| asthmatic-children| systemic reactions| young-children| position paper| efficacy| rhinoconjunctivitis.	SEP-2005	house-dust-mite| double-blind| allergen immunotherapy| therapeutic vaccines| asthmatic-children| systemic reactions| young-children| position paper| efficacy| rhinoconjunctivitis	Fiocchi, A; Pajno, G; La Grutta, S; Pezzuto, F; Incorvaia, C; Sensi, L; Marcucci, F; Frati, F	Safety of sublingual-swallow immunotherapy in children aged 3 to 7 years		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		HOUSE-DUST-MITE; DOUBLE-BLIND; ALLERGEN IMMUNOTHERAPY; THERAPEUTIC VACCINES; ASTHMATIC-CHILDREN; SYSTEMIC REACTIONS; YOUNG-CHILDREN; POSITION PAPER; EFFICACY; RHINOCONJUNCTIVITIS	Background: The minimum age to start specific immunotherapy with inhalant allergens in children has not been clearly established, and position papers discourage its use in children younger than 5 years. Objective: To assess the safety of high-dose sublingual-swallow immunotherapy (SLIT) in a group of children younger than 5 years. Methods: Sixty-five children (51 boys and 14 girls; age range, 38-80 months; mean +/- SD age, 60 +/- 10 years; median age, 60 months) were included in this observational study. They were treated with SLIT with a build-up phase of 11 days, culminating in a top dose of 300 IR (index of reactivity) and a maintenance phase of 300 IR 3 times a week. The allergens used were house dust mites in 42 patients, grass pollen in 11 patients, olive pollen in 5 patients, Parietaria pollen in 4 patients, and cypress pollen in 3 patients. All adverse reactions and changes in the treatment schedule were compared in 2 subgroups: children 38 to 60 months old and children 61 to 80 months old. Results: The average cumulative dose of SLIT was 36,900 IR. Adverse reactions were observed in 11 children, none of them severe enough to require discontinuation of immunotherapy. Six reactions occurred in the 60 months or younger age group and 7 in the older than 60 months age group, with no differences between these 2 groups. Conclusion: High-dose immunotherapy in children younger than 5 years does not cause more adverse reactions than in children aged 5 to 7 years. There is no reason to forbear studies on safety and efficacy of these preparations in young children.	30	76	2005	5		Allergy; Immunology
Specific IgE and IgG antibody-binding patterns to recombinant cockroach allergens. Background: The specificity of serum antibody responses to different cockroach allergens has not been studied. Objective: We sought to quantitate serum IgE and IgG antibodies to a panel of purified cockroach allergens among cockroach-sensitized subjects. Methods: IgE antibodies to recombinant cockroach allergens (rBla g 1, rBla g 2, rBla g 4, rBla g 5, and rPer a 7) were measured in sera containing IgE antibodies to Blattella germanica extract (n = 118) by using a streptavidin CAP assay and a multiplex flow cytometric assay. Specific IgG antibodies were determined by using radioimmuno-precipitation techniques. Results: Specific IgE antibodies measured by means of CAP assay and multiplex assay were strongly correlated (r = 0.8, P < .001). The sum of IgE antibodies (in international units per milliliter) against all 5 allergens equated to IgE antibodies to cockroach extract. Although the prevalence of IgE antibodies was highest for rBla g 2 (54.4%) and rBla g 5 (37.4%), patterns of IgE antibody binding were unique to each subject. Surprisingly, only 16% of cockroach-sensitized subjects with IgE antibodies to house dust mite exhibited IgE antibody binding to cockroach tropomyosin (rPer a 7). Specific IgE antibodies were associated with increased IgG antibody levels, although detection of IgG in the absence of IgE was not uncommon. Conclusion: The techniques described offer a new approach for defining the hierarchy of purified allergens. IgE antibodies directed against 5 allergens constitute the majority of the IgE antibody repertoire for cockroach. Such distinct, patterns of IgE-IgG responsiveness to different cockroach allergens highlight the complexity of B-cell responses to environmental allergens.. cockroach| asthma| allergens| troponryosin| ige antibody| igg antibody| multiplex|inner-city children| flow-cytometric assay| american cockroach| house-dust| dermatophagoides-pteronyssinus| blattella-germanica| molecular-cloning| major allergen| risk-factors| asthma.	APR-2005	cockroach| asthma| allergens| troponryosin| ige antibody| igg antibody| multiplex|inner-city children| flow-cytometric assay| american cockroach| house-dust| dermatophagoides-pteronyssinus| blattella-germanica| molecular-cloning| major allergen| risk-factors| asthma	Satinover, SM; Reefer, AJ; Pomes, A; Chapman, MD; Platts-Mills, TAE; Woodfolk, JA	Specific IgE and IgG antibody-binding patterns to recombinant cockroach allergens		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	cockroach; asthma; allergens; troponryosin; IgE antibody; IgG antibody; multiplex	INNER-CITY CHILDREN; FLOW-CYTOMETRIC ASSAY; AMERICAN COCKROACH; HOUSE-DUST; DERMATOPHAGOIDES-PTERONYSSINUS; BLATTELLA-GERMANICA; MOLECULAR-CLONING; MAJOR ALLERGEN; RISK-FACTORS; ASTHMA	Background: The specificity of serum antibody responses to different cockroach allergens has not been studied. Objective: We sought to quantitate serum IgE and IgG antibodies to a panel of purified cockroach allergens among cockroach-sensitized subjects. Methods: IgE antibodies to recombinant cockroach allergens (rBla g 1, rBla g 2, rBla g 4, rBla g 5, and rPer a 7) were measured in sera containing IgE antibodies to Blattella germanica extract (n = 118) by using a streptavidin CAP assay and a multiplex flow cytometric assay. Specific IgG antibodies were determined by using radioimmuno-precipitation techniques. Results: Specific IgE antibodies measured by means of CAP assay and multiplex assay were strongly correlated (r = 0.8, P < .001). The sum of IgE antibodies (in international units per milliliter) against all 5 allergens equated to IgE antibodies to cockroach extract. Although the prevalence of IgE antibodies was highest for rBla g 2 (54.4%) and rBla g 5 (37.4%), patterns of IgE antibody binding were unique to each subject. Surprisingly, only 16% of cockroach-sensitized subjects with IgE antibodies to house dust mite exhibited IgE antibody binding to cockroach tropomyosin (rPer a 7). Specific IgE antibodies were associated with increased IgG antibody levels, although detection of IgG in the absence of IgE was not uncommon. Conclusion: The techniques described offer a new approach for defining the hierarchy of purified allergens. IgE antibodies directed against 5 allergens constitute the majority of the IgE antibody repertoire for cockroach. Such distinct, patterns of IgE-IgG responsiveness to different cockroach allergens highlight the complexity of B-cell responses to environmental allergens.	34	76	2005	7	10.1016/j.jaci.2005.01.018	Allergy; Immunology
Use of beta-blockers during immunotherapy for Hymenoptera venom allergy. Background: B-Blockers may aggravate anaphylactic reactions and interfere with treatment. There is therefore concern about their use in patients who have a history of anaphylaxis or are on allergen immunotherapy. Immunotherapy is the best available treatment for prevention of life-threatening anaphylaxis to Hymenoptera stings, which is often observed in elderly patients who have cardiovascular disease and therefore are on beta-blocker treatment. Objective: To analyze the risk of beta-blocker treatment during venom immunotherapy. Methods: We screened all 1682 patients with Hymenoptera venom allergy seen during a period of 34 months for immunotherapy, cardiovascular disease, and treatment with beta-blockers. Results: Of the 1389 patients in whom immunotherapy was recommended, 11.2% had cardiovascular disease, and 44 of these were on beta-blockers before immunotherapy. In 31 of those, the drug was replaced before starting treatment. In 3 with coronary heart disease and I with severe ventricular arrhythmia, the drug was continued throughout immunotherapy. In 9, it was reintroduced after reaching the maintenance dose. In an additional 12 patients, beta-blockers were newly started during immunotherapy. Of 25 patients on beta-blockers during immunotherapy, 3 (12%) developed allergic side effects, compared with 23 (16.7%) of 117 with cardiovascular disease but without beta-blockers. Systemic allergic symptoms after re-exposure by sting challenge or field sting were observed in 1 of 7 (14.3%) with and 4 of 29 (13.8%) without beta-blockade. No severe reactions to treatment or sting reexposure were observed in patients with beta-blockade. Conclusion: Combination of beta-blockers with venom immunotherapy may be indicated in heavily exposed patients with severe cardiovascular disease.. anaphylaxis| beta-blockers| hymenoptera venom immunotherapy|fatal anaphylactic reactions| adrenergic-blockade| heart-failure| risk| histamine| efficacy| therapy| safety| drugs.	MAR-2005	anaphylaxis| beta-blockers| hymenoptera venom immunotherapy|fatal anaphylactic reactions| adrenergic-blockade| heart-failure| risk| histamine| efficacy| therapy| safety| drugs	Muller, UR; Haeberli, G	Use of beta-blockers during immunotherapy for Hymenoptera venom allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	anaphylaxis; beta-blockers; hymenoptera venom immunotherapy	FATAL ANAPHYLACTIC REACTIONS; ADRENERGIC-BLOCKADE; HEART-FAILURE; RISK; HISTAMINE; EFFICACY; THERAPY; SAFETY; DRUGS	Background: B-Blockers may aggravate anaphylactic reactions and interfere with treatment. There is therefore concern about their use in patients who have a history of anaphylaxis or are on allergen immunotherapy. Immunotherapy is the best available treatment for prevention of life-threatening anaphylaxis to Hymenoptera stings, which is often observed in elderly patients who have cardiovascular disease and therefore are on beta-blocker treatment. Objective: To analyze the risk of beta-blocker treatment during venom immunotherapy. Methods: We screened all 1682 patients with Hymenoptera venom allergy seen during a period of 34 months for immunotherapy, cardiovascular disease, and treatment with beta-blockers. Results: Of the 1389 patients in whom immunotherapy was recommended, 11.2% had cardiovascular disease, and 44 of these were on beta-blockers before immunotherapy. In 31 of those, the drug was replaced before starting treatment. In 3 with coronary heart disease and I with severe ventricular arrhythmia, the drug was continued throughout immunotherapy. In 9, it was reintroduced after reaching the maintenance dose. In an additional 12 patients, beta-blockers were newly started during immunotherapy. Of 25 patients on beta-blockers during immunotherapy, 3 (12%) developed allergic side effects, compared with 23 (16.7%) of 117 with cardiovascular disease but without beta-blockers. Systemic allergic symptoms after re-exposure by sting challenge or field sting were observed in 1 of 7 (14.3%) with and 4 of 29 (13.8%) without beta-blockade. No severe reactions to treatment or sting reexposure were observed in patients with beta-blockade. Conclusion: Combination of beta-blockers with venom immunotherapy may be indicated in heavily exposed patients with severe cardiovascular disease.	37	76	2005	5	10.1016/j.jsci.2004.11.012	Allergy; Immunology
Comparative health impact assessment of local and regional particulate air pollutants in Scandinavia. The ongoing program Clean Air for Europe (CAFE) is an initiative from the EU Commission to establish a coordinated effort to reach better air quality in the EU. The focus is on particulate matter as it has been shown to have large impact on human health. CAFE requested that WHO make a review of the latest findings on air pollutants and health to facilitate assessments of the different air pollutants and their health effects. The WHO review project on health aspects of air pollution in Europe confirmed that exposure to particulate matter (PM), despite the lower levels we face today, still poses a significant risk to human health. Using the recommended uniform risk coefficients for health impact assessment of PM, regardless of sources, premature mortality related to long-range transported anthropogenic particles has been estimated to be about 3500 deaths per year for the Swedish population, corresponding to a reduction in life expectancy of up to about seven months. The influence of local sources is more difficult to estimate due to large uncertainties when linking available risk coefficients to exposure data, but the estimates indicate about 1800 deaths brought forward each year with a life expectancy reduction of about 2-3 months. However, some sectors of the population are exposed to quite high locally induced concentrations and are likely to suffer excessive reductions in life expectancy. Since the literature increasingly supports assumptions that combustion related particles are associated with higher relative risks, further studies may shift the focus for abatement strategies. CAFE sets out to establish a general cost effective abatement strategy for atmospheric particles. Our results, based on studies of background exposure, show that long-range transported sulfate rich particles dominate the health effects of PM in Sweden. The same results would be found for the whole of Scandinavia and many countries influenced by transboundary air pollution. However, several health studies, including epidemiological studies with a finer spatial resolution, indicate that engine exhaust particles are more damaging to health than other particles. These contradictory findings must be understood and source specific risk estimates have to be established by expert bodies, otherwise it will not be possible to find the most cost effective abatement strategy for Europe. We are not happy with today's situation where every strategy to reduce PM concentrations is estimated to have the same impact per unit change in the mass concentration. Obviously there is a striking need to introduce more specific exposure variables and a higher geographical resolution in epidemiology as well as in health impact assessments.. daily mortality| respiratory symptoms| background sites| asthma symptoms| wood combustion| boundary-layer| pollution| particles| urban| association.	FEB-2005	daily mortality| respiratory symptoms| background sites| asthma symptoms| wood combustion| boundary-layer| pollution| particles| urban| association	Forsberg, B; Hansson, HC; Johansson, C; Areskoug, H; Persson, K; Jarvholm, B	Comparative health impact assessment of local and regional particulate air pollutants in Scandinavia		AMBIO		DAILY MORTALITY; RESPIRATORY SYMPTOMS; BACKGROUND SITES; ASTHMA SYMPTOMS; WOOD COMBUSTION; BOUNDARY-LAYER; POLLUTION; PARTICLES; URBAN; ASSOCIATION	The ongoing program Clean Air for Europe (CAFE) is an initiative from the EU Commission to establish a coordinated effort to reach better air quality in the EU. The focus is on particulate matter as it has been shown to have large impact on human health. CAFE requested that WHO make a review of the latest findings on air pollutants and health to facilitate assessments of the different air pollutants and their health effects. The WHO review project on health aspects of air pollution in Europe confirmed that exposure to particulate matter (PM), despite the lower levels we face today, still poses a significant risk to human health. Using the recommended uniform risk coefficients for health impact assessment of PM, regardless of sources, premature mortality related to long-range transported anthropogenic particles has been estimated to be about 3500 deaths per year for the Swedish population, corresponding to a reduction in life expectancy of up to about seven months. The influence of local sources is more difficult to estimate due to large uncertainties when linking available risk coefficients to exposure data, but the estimates indicate about 1800 deaths brought forward each year with a life expectancy reduction of about 2-3 months. However, some sectors of the population are exposed to quite high locally induced concentrations and are likely to suffer excessive reductions in life expectancy. Since the literature increasingly supports assumptions that combustion related particles are associated with higher relative risks, further studies may shift the focus for abatement strategies. CAFE sets out to establish a general cost effective abatement strategy for atmospheric particles. Our results, based on studies of background exposure, show that long-range transported sulfate rich particles dominate the health effects of PM in Sweden. The same results would be found for the whole of Scandinavia and many countries influenced by transboundary air pollution. However, several health studies, including epidemiological studies with a finer spatial resolution, indicate that engine exhaust particles are more damaging to health than other particles. These contradictory findings must be understood and source specific risk estimates have to be established by expert bodies, otherwise it will not be possible to find the most cost effective abatement strategy for Europe. We are not happy with today's situation where every strategy to reduce PM concentrations is estimated to have the same impact per unit change in the mass concentration. Obviously there is a striking need to introduce more specific exposure variables and a higher geographical resolution in epidemiology as well as in health impact assessments.	49	76	2005	9	10.1639/0044-7447(2005)034[0011:CHIAOL]2.0.CO;2	Engineering; Environmental Sciences & Ecology
Country of birth as a risk factor for asthma among Mexican Americans. In the United States, among Hispanics, Mexican Americans have the lowest rate of asthma. However, this population includes Mexican Americans born in the United States and in Mexico, and risk factors that might impact the prevalence of asthma differ between these groups. To determine the prevalence of and risk factors for asthma among U.S.- and Mexican-born Mexican Americans, we analyzed data from two U.S. surveys that included 4,574 persons who self-reported their ethnicity as Mexican American from the Third National Health and Nutrition Examination Survey (NHANES III) 1998-1994 and 12,980 persons who self-reported their ethnicity as Mexican American from National Health Interview Survey (NHIS) 1997-2001. U.S.-born Mexican Americans were more likely than Mexican-born Mexican Americans to report ever having asthma in both the NHANES III (7% [SE 0.5] vs. 3% [SE 0.3], p < 0.001) and NHIS surveys (8.1% [0.4] vs. 2.5% [0.2], p < 0.001). In a multivariate regression model controlling for multiple demographic variables and health care, the risk for asthma was higher among U.S.-born Mexicans in NHANES III (odds ratio 2.1, 95% confidence interval 1.4-3.3) and NHIS (odds ratio 2.7, 95% confidence interval 1.6-5.5). In conclusion, the prevalence of asthma was higher in U.S.-born than in Mexican-born Mexican Americans. This finding highlights the importance of environmental exposures in developing asthma in a migratory population.. asthma| mexican americans| migration|body-mass index| nhanes-iii| respiratory symptoms| serum ige| us adults| immigrants| prevalence| allergy| health| age.	JAN 15-2005	asthma| mexican americans| migration|body-mass index| nhanes-iii| respiratory symptoms| serum ige| us adults| immigrants| prevalence| allergy| health| age	Holguin, F; Mannino, DM; Anto, J; Mott, J; Ford, ES; Teague, WG; Redd, SC; Romieu, I	Country of birth as a risk factor for asthma among Mexican Americans		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; Mexican Americans; migration	BODY-MASS INDEX; NHANES-III; RESPIRATORY SYMPTOMS; SERUM IGE; US ADULTS; IMMIGRANTS; PREVALENCE; ALLERGY; HEALTH; AGE	In the United States, among Hispanics, Mexican Americans have the lowest rate of asthma. However, this population includes Mexican Americans born in the United States and in Mexico, and risk factors that might impact the prevalence of asthma differ between these groups. To determine the prevalence of and risk factors for asthma among U.S.- and Mexican-born Mexican Americans, we analyzed data from two U.S. surveys that included 4,574 persons who self-reported their ethnicity as Mexican American from the Third National Health and Nutrition Examination Survey (NHANES III) 1998-1994 and 12,980 persons who self-reported their ethnicity as Mexican American from National Health Interview Survey (NHIS) 1997-2001. U.S.-born Mexican Americans were more likely than Mexican-born Mexican Americans to report ever having asthma in both the NHANES III (7% [SE 0.5] vs. 3% [SE 0.3], p < 0.001) and NHIS surveys (8.1% [0.4] vs. 2.5% [0.2], p < 0.001). In a multivariate regression model controlling for multiple demographic variables and health care, the risk for asthma was higher among U.S.-born Mexicans in NHANES III (odds ratio 2.1, 95% confidence interval 1.4-3.3) and NHIS (odds ratio 2.7, 95% confidence interval 1.6-5.5). In conclusion, the prevalence of asthma was higher in U.S.-born than in Mexican-born Mexican Americans. This finding highlights the importance of environmental exposures in developing asthma in a migratory population.	38	76	2005	6	10.1164/rccm.200402-143OC	General & Internal Medicine; Respiratory System
Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases. Background The fear of side-effects has led to strict regulations preventing a more widespread use of specific immunotherapy (SIT) in some countries, in spite of the low risk of systemic reactions (SRs) reported in well-controlled studies. The goal of the study was to carry out a prospective and multi-centric trial to evaluate the safety, risk factors and compliance degree of commercially available SIT. Materials and methods The study was carried out in 14 allergy departments from Spain. Four-hundred and eighty-eight patients with rhinitis and/or asthma were submitted to treatment with biologically standardized allergen extracts commercially available. They were administered following the European Academy of Allergy and Clinical Immunology guidelines. Results Four hundred and twenty-three patients (86.7%) completed the treatment and remained under control at the end of the trial. Out of 17 526 administered doses, 17 368 doses (99.1%) were not associated with a reaction. Eighteen patients (3.7%) experienced 53 (0.3% of the doses) SRs. All immediate SRs were mild or moderate and responded well to ordinary treatment measures. There were no fatal reactions, anaphylactic shock or life-threatening reactions. A higher ratio of SRs was found among asthmatic and dust mite allergic patients, although multi-variable logistic analysis did not demonstrate any risk factor associated with SRs. There was also a subgroup of patients at risk for recurrent reactions, and therefore 40% of SRs had been avoided if the maximal number of SRs had been previously limited to only three SRs. Conclusions This multi-centric study showed that SIT was a safe treatment with a very good compliance. Future guidelines of SIT should limit the maximal number of SRs.. asthma| compliance| immunotherapy| mite| pollen| rhinitis| safety| side-effects|systemic reactions| asthma| fatalities| extracts.	APR-2004	asthma| compliance| immunotherapy| mite| pollen| rhinitis| safety| side-effects|systemic reactions| asthma| fatalities| extracts	Moreno, C; Cuesta-Herranz, J; Fernandez-Tavora, L; Alvarez-Cuesta, E	Immunotherapy safety: a prospective multi-centric monitoring study of biologically standardized therapeutic vaccines for allergic diseases		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; compliance; immunotherapy; mite; pollen; rhinitis; safety; side-effects	SYSTEMIC REACTIONS; ASTHMA; FATALITIES; EXTRACTS	Background The fear of side-effects has led to strict regulations preventing a more widespread use of specific immunotherapy (SIT) in some countries, in spite of the low risk of systemic reactions (SRs) reported in well-controlled studies. The goal of the study was to carry out a prospective and multi-centric trial to evaluate the safety, risk factors and compliance degree of commercially available SIT. Materials and methods The study was carried out in 14 allergy departments from Spain. Four-hundred and eighty-eight patients with rhinitis and/or asthma were submitted to treatment with biologically standardized allergen extracts commercially available. They were administered following the European Academy of Allergy and Clinical Immunology guidelines. Results Four hundred and twenty-three patients (86.7%) completed the treatment and remained under control at the end of the trial. Out of 17 526 administered doses, 17 368 doses (99.1%) were not associated with a reaction. Eighteen patients (3.7%) experienced 53 (0.3% of the doses) SRs. All immediate SRs were mild or moderate and responded well to ordinary treatment measures. There were no fatal reactions, anaphylactic shock or life-threatening reactions. A higher ratio of SRs was found among asthmatic and dust mite allergic patients, although multi-variable logistic analysis did not demonstrate any risk factor associated with SRs. There was also a subgroup of patients at risk for recurrent reactions, and therefore 40% of SRs had been avoided if the maximal number of SRs had been previously limited to only three SRs. Conclusions This multi-centric study showed that SIT was a safe treatment with a very good compliance. Future guidelines of SIT should limit the maximal number of SRs.	23	76	2004	5	10.1111/j.1365-2222.2004.1819.x	Allergy; Immunology
Stress enhances airway reactivity and airway inflammation in an animal model of allergic bronchial asthma. Objective: Despite the long-standing clinical assumption that stress and asthma morbidity are associated, convincing experimental evidence on mechanisms has been unavailable. A wide range of immunological, endocrinological, and neuronal pathways are known to mediate and modulate a systemic stress response. Interestingly, most of these mediators play a crucial role in initiating and perpetuating symptoms associated with bronchial asthma. To explore potential mechanisms linking stress to asthma exacerbation we developed an animal model that combines allergic airway inflammation and exposure to stress. Methods: CBA/J mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and challenged with OVA aerosol via the airways. Additionally, some mice were stressed by exposure to an ultrasonic stressor. Airway hyperreactivity (AHR) was measured in vitro by electric field stimulation (EFS) of tracheal smooth muscle elements. Bronchoalveolar lavage fluid (BAL) was obtained and cell numbers determined. Cytokine levels of IL-4, IL-5, and IFN-gamma in BAL were determined by ELISA. Results: Our findings demonstrate that exogenously applied stress dramatically enhances airway reactivity in OVA-sensitized and challenged mice. Further, stress significantly increases allergen-induced airway inflammation identified by increased leukocyte (ie, eosinophil) numbers in bronchoalveolar lavage fluids. Conclusions: We found further evidence that stress can indeed exacerbate airway hyperreactivity and airway inflammation in an animal model of allergic bronchial asthma and now introduce a novel murine model to identify stress-triggered pathways, including mediators as neurohormones, neuropeptides, and markers of inflammation.. sonic stress| allergic asthma| airway inflammation| airway hyperreactivity| mouse model|m-2 receptor dysfunction| psychosocial stress| human eosinophils| psychological stress| cytokine production| triggered abortion| atopic-dermatitis| breast-cancer| guinea-pigs| mice.	SEP-OCT-2003	sonic stress| allergic asthma| airway inflammation| airway hyperreactivity| mouse model|m-2 receptor dysfunction| psychosocial stress| human eosinophils| psychological stress| cytokine production| triggered abortion| atopic-dermatitis| breast-cancer| guinea-pigs| mice	Joachim, RA; Quarcoo, D; Arck, PC; Herz, U; Renz, H; Klapp, BF	Stress enhances airway reactivity and airway inflammation in an animal model of allergic bronchial asthma		PSYCHOSOMATIC MEDICINE	sonic stress; allergic asthma; airway inflammation; airway hyperreactivity; mouse model	M-2 RECEPTOR DYSFUNCTION; PSYCHOSOCIAL STRESS; HUMAN EOSINOPHILS; PSYCHOLOGICAL STRESS; CYTOKINE PRODUCTION; TRIGGERED ABORTION; ATOPIC-DERMATITIS; BREAST-CANCER; GUINEA-PIGS; MICE	Objective: Despite the long-standing clinical assumption that stress and asthma morbidity are associated, convincing experimental evidence on mechanisms has been unavailable. A wide range of immunological, endocrinological, and neuronal pathways are known to mediate and modulate a systemic stress response. Interestingly, most of these mediators play a crucial role in initiating and perpetuating symptoms associated with bronchial asthma. To explore potential mechanisms linking stress to asthma exacerbation we developed an animal model that combines allergic airway inflammation and exposure to stress. Methods: CBA/J mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and challenged with OVA aerosol via the airways. Additionally, some mice were stressed by exposure to an ultrasonic stressor. Airway hyperreactivity (AHR) was measured in vitro by electric field stimulation (EFS) of tracheal smooth muscle elements. Bronchoalveolar lavage fluid (BAL) was obtained and cell numbers determined. Cytokine levels of IL-4, IL-5, and IFN-gamma in BAL were determined by ELISA. Results: Our findings demonstrate that exogenously applied stress dramatically enhances airway reactivity in OVA-sensitized and challenged mice. Further, stress significantly increases allergen-induced airway inflammation identified by increased leukocyte (ie, eosinophil) numbers in bronchoalveolar lavage fluids. Conclusions: We found further evidence that stress can indeed exacerbate airway hyperreactivity and airway inflammation in an animal model of allergic bronchial asthma and now introduce a novel murine model to identify stress-triggered pathways, including mediators as neurohormones, neuropeptides, and markers of inflammation.	51	76	2003	5	10.1097/01.PSY.0000088582.50468.A3	Psychiatry; Psychology
Early endotoxin exposure and atopy development in infants: results of a birth cohort study. Background Exposure to endotoxin in childhood is currently discussed to protect from the development of allergic diseases. Objective To study the effect of early endotoxin exposure on incidence of atopic sensitization, atopic dermatitis and wheezing until the age of 2 years in infants with different risk status in terms of parental atopy. Methods Data of 1942 infants of an ongoing birth cohort study were analysed by logistic regression. Endotoxin was measured in settled dust of the mothers' mattresses at infants' age of 3 months. Data on allergic symptoms and physicians' diagnoses were gathered by questionnaire. Sensitization to common food and inhalant allergens was assessed by specific serum IgE. Results High endotoxin levels increased the risk of repeated wheeze [adjusted odds ratio (OR) for 4th exposure quartile ((Q4)) 1.52, 95% confidence interval (CI) 1.08-2.14], but were associated with neither sensitization to food allergens nor atopic dermatitis. Stratification by parental atopy showed that there was an association of endotoxin exposure with incidence of repeated wheeze as well as with sensitization to inhalant allergens (P for trend = 0.008 and 0.044, respectively) only in infants with parental atopy, with the highest risk in the 4th exposure quartile (repeated wheeze: ORQ4 1.77, 95% CI 1.14-2.73; sensitization to inhalant allergens: ORQ4 1.69, 95% CI 0.70-4.11). Conclusion Early endotoxin exposure in terms of mattress dust endotoxin levels seemed to increase the risk of atopic reactions to inhalant allergens at the age of 2 years, especially in infants at risk due to parental atopy. Our data disagree with an early protective effect of endotoxin on atopy development until the age of 2 years.. allergy| asthma| hygiene hypothesis|house-dust endotoxin| inflammatory response| inhaled endotoxin| early-life| asthma| children| allergy| sensitization| risk| pets.	JUN-2003	allergy| asthma| hygiene hypothesis|house-dust endotoxin| inflammatory response| inhaled endotoxin| early-life| asthma| children| allergy| sensitization| risk| pets	Bolte, G; Bischof, W; Borte, M; Lehmann, I; Wichmann, HE; Heinrich, J	Early endotoxin exposure and atopy development in infants: results of a birth cohort study		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; asthma; hygiene hypothesis	HOUSE-DUST ENDOTOXIN; INFLAMMATORY RESPONSE; INHALED ENDOTOXIN; EARLY-LIFE; ASTHMA; CHILDREN; ALLERGY; SENSITIZATION; RISK; PETS	Background Exposure to endotoxin in childhood is currently discussed to protect from the development of allergic diseases. Objective To study the effect of early endotoxin exposure on incidence of atopic sensitization, atopic dermatitis and wheezing until the age of 2 years in infants with different risk status in terms of parental atopy. Methods Data of 1942 infants of an ongoing birth cohort study were analysed by logistic regression. Endotoxin was measured in settled dust of the mothers' mattresses at infants' age of 3 months. Data on allergic symptoms and physicians' diagnoses were gathered by questionnaire. Sensitization to common food and inhalant allergens was assessed by specific serum IgE. Results High endotoxin levels increased the risk of repeated wheeze [adjusted odds ratio (OR) for 4th exposure quartile ((Q4)) 1.52, 95% confidence interval (CI) 1.08-2.14], but were associated with neither sensitization to food allergens nor atopic dermatitis. Stratification by parental atopy showed that there was an association of endotoxin exposure with incidence of repeated wheeze as well as with sensitization to inhalant allergens (P for trend = 0.008 and 0.044, respectively) only in infants with parental atopy, with the highest risk in the 4th exposure quartile (repeated wheeze: ORQ4 1.77, 95% CI 1.14-2.73; sensitization to inhalant allergens: ORQ4 1.69, 95% CI 0.70-4.11). Conclusion Early endotoxin exposure in terms of mattress dust endotoxin levels seemed to increase the risk of atopic reactions to inhalant allergens at the age of 2 years, especially in infants at risk due to parental atopy. Our data disagree with an early protective effect of endotoxin on atopy development until the age of 2 years.	36	76	2003	7	10.1046/j.1365-2222.2003.01665.x	Allergy; Immunology
"Symposium: Understanding asthma pathophysiology. Asthma is best described as a chronic disease that involves inflammation of the pulmonary airways and bronchial hyperresponsiveness that results in the clinical expression of a lower airway obstruction that usually is reversible. Physiologically, bronchial hyperresponsiveness is documented by decreased bronchial airflow after bronchoprovocation with methacholine or histamine. Other triggers that provoke airway obstruction include cold air, exercise, viral upper respiratory infection, cigarette smoke, and respiratory allergens. Bronchial provocation with allergen induces a prompt early phase immunoglobulin E (IgE)-mediated decrease in bronchial airflow (forced expiratory volume in 1 second) followed in many patients by a late-phase IgE-mediated reaction with a decrease in bronchial airflow for 4-8 hours. The gross pathology of asthmatic airways displays lung hyperinflation, smooth muscle hypertrophy, lamina reticularis thickening, mucosal edema, epithelial cell sloughing, cilia cell disruption, and mucus gland hypersecretion. Microscopically, asthma is characterized by the presence of increased numbers of eosinophils, neutrophils, lymphocytes, and plasma cells in the bronchial tissues, bronchial secretions, and mucus. Initially, there is recruitment of leukocytes from the bloodstream to the airway by activated CD, T-lymphocytes. The activated T-lymphocytes also direct the release of inflammatory mediators from eosinophils, mast cells, and lymphocytes. In addition, the subclass 2 helper T-lymphocytes subset of activated T-lymphocytes produces interleukin (IL)-4, IL-5, and IL-13. IL-4 in conjunction with IL-13 signals the switch from IgM to IgE antibodies. The cross-linkage of two IgE molecules by allergen causes mast cells to degranulate, releasing histamine, leukotrienes, and other mediators that perpetuate the airway inflammation. IL-5 activates the recruitment and activation of eosinophils. The activated mast cells and eosinophils also generate their cytokines that help to perpetuate the inflammation. Regardless of the triggers of asthma, the repeated cycles of inflammation in the lungs with injury to the pulmonary tissues followed by repair may produce long-term structural changes (""remodeling"") of the airways. This review will discuss in greater detail the relationships of inflammation and airway hyperresponsiveness to the pathophysiology of asthma.. airway smooth-muscle| inflammation| hyperresponsiveness| adults| life."	MAR-APR-2003	airway smooth-muscle| inflammation| hyperresponsiveness| adults| life	Fireman, P	Symposium: Understanding asthma pathophysiology		ALLERGY AND ASTHMA PROCEEDINGS		AIRWAY SMOOTH-MUSCLE; INFLAMMATION; HYPERRESPONSIVENESS; ADULTS; LIFE	"Asthma is best described as a chronic disease that involves inflammation of the pulmonary airways and bronchial hyperresponsiveness that results in the clinical expression of a lower airway obstruction that usually is reversible. Physiologically, bronchial hyperresponsiveness is documented by decreased bronchial airflow after bronchoprovocation with methacholine or histamine. Other triggers that provoke airway obstruction include cold air, exercise, viral upper respiratory infection, cigarette smoke, and respiratory allergens. Bronchial provocation with allergen induces a prompt early phase immunoglobulin E (IgE)-mediated decrease in bronchial airflow (forced expiratory volume in 1 second) followed in many patients by a late-phase IgE-mediated reaction with a decrease in bronchial airflow for 4-8 hours. The gross pathology of asthmatic airways displays lung hyperinflation, smooth muscle hypertrophy, lamina reticularis thickening, mucosal edema, epithelial cell sloughing, cilia cell disruption, and mucus gland hypersecretion. Microscopically, asthma is characterized by the presence of increased numbers of eosinophils, neutrophils, lymphocytes, and plasma cells in the bronchial tissues, bronchial secretions, and mucus. Initially, there is recruitment of leukocytes from the bloodstream to the airway by activated CD, T-lymphocytes. The activated T-lymphocytes also direct the release of inflammatory mediators from eosinophils, mast cells, and lymphocytes. In addition, the subclass 2 helper T-lymphocytes subset of activated T-lymphocytes produces interleukin (IL)-4, IL-5, and IL-13. IL-4 in conjunction with IL-13 signals the switch from IgM to IgE antibodies. The cross-linkage of two IgE molecules by allergen causes mast cells to degranulate, releasing histamine, leukotrienes, and other mediators that perpetuate the airway inflammation. IL-5 activates the recruitment and activation of eosinophils. The activated mast cells and eosinophils also generate their cytokines that help to perpetuate the inflammation. Regardless of the triggers of asthma, the repeated cycles of inflammation in the lungs with injury to the pulmonary tissues followed by repair may produce long-term structural changes (""remodeling"") of the airways. This review will discuss in greater detail the relationships of inflammation and airway hyperresponsiveness to the pathophysiology of asthma."	25	76	2003	5		Allergy
Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy?. Background The pathophysiology of idiopathic rhinitis is unknown although evidence is accumulating to suggest that many patients may have a localized form of allergic rhinitis in the absence of other atopic symptoms and markers. This study compares detailed nasal challenge results obtained from patients with idiopathic rhinitis to those of atopic and normal controls. Methods Patients with idiopathic rhinitis (n = 23), perennial allergic rhinitis (n = 8) and normal controls (n = 8) underwent a normal saline challenge to exclude hyper-reactivity and then bilateral nasal allergen challenges. Nasal patency was assessed by anterior active rhinomanometry. Results All of the patients with atopic rhinitis demonstrated positive bilateral allergen challenges. All normal control subjects had bilateral negative challenges. Two patients in the idiopathic group tested positively to saline and were excluded from further study with 62% of the remainder testing positive to allergens. Of the idiopathic patients testing positive, 85% were sensitive to house dust mite. Conclusion A significant proportion of patients with idiopathic rhinitis have positive nasal challenges, the vast majority to house dust mite allergen. These findings add to the weight of evidence that suggests 'localized allergy' may exist in the absence of systemic atopic markers.. allergy| idiopathic rhinitis| non-allergic rhinitis| allergen challenge| rhinomanometry| vasomotor rhinitis|local ige production| systematic evaluation| nonallergic rhinitis| preliminary criteria| acoustic rhinometry| clinical-parameters| perennial rhinitis| provocation test| skin-tests| air-flow.	OCT-2002	allergy| idiopathic rhinitis| non-allergic rhinitis| allergen challenge| rhinomanometry| vasomotor rhinitis|local ige production| systematic evaluation| nonallergic rhinitis| preliminary criteria| acoustic rhinometry| clinical-parameters| perennial rhinitis| provocation test| skin-tests| air-flow	Carney, AS; Powe, DG; Huskisson, RS; Jones, NS	Atypical nasal challenges in patients with idiopathic rhinitis: more evidence for the existence of allergy in the absence of atopy?		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; idiopathic rhinitis; non-allergic rhinitis; allergen challenge; rhinomanometry; vasomotor rhinitis	LOCAL IGE PRODUCTION; SYSTEMATIC EVALUATION; NONALLERGIC RHINITIS; PRELIMINARY CRITERIA; ACOUSTIC RHINOMETRY; CLINICAL-PARAMETERS; PERENNIAL RHINITIS; PROVOCATION TEST; SKIN-TESTS; AIR-FLOW	Background The pathophysiology of idiopathic rhinitis is unknown although evidence is accumulating to suggest that many patients may have a localized form of allergic rhinitis in the absence of other atopic symptoms and markers. This study compares detailed nasal challenge results obtained from patients with idiopathic rhinitis to those of atopic and normal controls. Methods Patients with idiopathic rhinitis (n = 23), perennial allergic rhinitis (n = 8) and normal controls (n = 8) underwent a normal saline challenge to exclude hyper-reactivity and then bilateral nasal allergen challenges. Nasal patency was assessed by anterior active rhinomanometry. Results All of the patients with atopic rhinitis demonstrated positive bilateral allergen challenges. All normal control subjects had bilateral negative challenges. Two patients in the idiopathic group tested positively to saline and were excluded from further study with 62% of the remainder testing positive to allergens. Of the idiopathic patients testing positive, 85% were sensitive to house dust mite. Conclusion A significant proportion of patients with idiopathic rhinitis have positive nasal challenges, the vast majority to house dust mite allergen. These findings add to the weight of evidence that suggests 'localized allergy' may exist in the absence of systemic atopic markers.	45	76	2002	5		Allergy; Immunology
Nonresponse in a community cohort study - Predictors and consequences for exposure-disease associations. We have assessed predictors for response in a Norwegian community cohort study, with an 11-year follow-up. We also examined to what extent the association of gender, age, and smoking to the incidence of respiratory symptoms and asthma differed if the analyses were based on the 65% (n = 2,079) initial responders, or were based on the 89% (n = 2,819) who responded after three reminders. The associations between the six symptoms/asthma and the gender, age, and smoking groups amounted to 42 odds ratios. The adjusted odds ratio for responding at follow-up was 1.39 (95% CI: 1.01, 1.90) for those being middle aged at baseline compared to younger subjects. The adjusted odds ratios for responding at follow-up for those being students, unemployed, or retired at baseline were 0.50 (95% CI: 0.35, 0.73), 0.29 (95% CI: 0.16, 0.55), 0.21 (95% CI: 0.13, 0.36), respectively, compared to being employed. Of the 42 odds ratios mentioned above, 25 differed less than 10% when comparing the initial and all respondents. Twelve differed 10-20% and five differed 20-45%. The study indicates that to ensure a high participation rate in a follow-up study one should pay special attention to those being late responders, unemployed, retired, or students at baseline. No overt differences were observed in the gender, age, and, smoking associations to the respiratory disorders when the analyses were based on the initial compared to all respondents. (C) 2002 Elsevier Science Inc. All rights reserved.. cohort study| questionnaire| response bias| odds ratio| asthma| respiratory symptoms| smoking|mail survey response| cardiovascular-disease| respiratory symptoms| questionnaire| smoking| health| bias| population| respondents| sweden.	AUG-2002	cohort study| questionnaire| response bias| odds ratio| asthma| respiratory symptoms| smoking|mail survey response| cardiovascular-disease| respiratory symptoms| questionnaire| smoking| health| bias| population| respondents| sweden	Eagan, TML; Eide, GE; Gulsvik, A; Bakke, PS	Nonresponse in a community cohort study - Predictors and consequences for exposure-disease associations		JOURNAL OF CLINICAL EPIDEMIOLOGY	cohort study; questionnaire; response bias; odds ratio; asthma; respiratory symptoms; smoking	MAIL SURVEY RESPONSE; CARDIOVASCULAR-DISEASE; RESPIRATORY SYMPTOMS; QUESTIONNAIRE; SMOKING; HEALTH; BIAS; POPULATION; RESPONDENTS; SWEDEN	We have assessed predictors for response in a Norwegian community cohort study, with an 11-year follow-up. We also examined to what extent the association of gender, age, and smoking to the incidence of respiratory symptoms and asthma differed if the analyses were based on the 65% (n = 2,079) initial responders, or were based on the 89% (n = 2,819) who responded after three reminders. The associations between the six symptoms/asthma and the gender, age, and smoking groups amounted to 42 odds ratios. The adjusted odds ratio for responding at follow-up was 1.39 (95% CI: 1.01, 1.90) for those being middle aged at baseline compared to younger subjects. The adjusted odds ratios for responding at follow-up for those being students, unemployed, or retired at baseline were 0.50 (95% CI: 0.35, 0.73), 0.29 (95% CI: 0.16, 0.55), 0.21 (95% CI: 0.13, 0.36), respectively, compared to being employed. Of the 42 odds ratios mentioned above, 25 differed less than 10% when comparing the initial and all respondents. Twelve differed 10-20% and five differed 20-45%. The study indicates that to ensure a high participation rate in a follow-up study one should pay special attention to those being late responders, unemployed, retired, or students at baseline. No overt differences were observed in the gender, age, and, smoking associations to the respiratory disorders when the analyses were based on the initial compared to all respondents. (C) 2002 Elsevier Science Inc. All rights reserved.	30	76	2002	7	10.1016/S0895-4356(02)00431-6	Health Care Sciences & Services; Public, Environmental & Occupational Health
The Seattle-King County Healthy Homes Project: Implementation of a comprehensive approach to improving indoor environmental quality for low-income children with asthma. Pediatric asthma is a growing public health issue, disproportionately affecting low-income people and people of color. Exposure to indoor asthma triggers plays an important role in the development and exacerbation of asthma. We describe the implementation of the Seattle-King County Healthy Homes Project, a randomized, controlled trial of an outreach/education intervention to improve asthma-related health status by reducing exposure to allergens and irritants in the home. We randomly assigned 274 low-income children with asthma ages 4-12 to either a high- or a low-intensity group. In the high-intensity group, community health workers called Community Home Environmental Specialists (CHES) conducted initial home environmental assessments, provided individualized action plans, and made additional visits over a 12-month period to provide education and social support, encouragement of participant actions, provision of materials to reduce exposures (including bedding encasements), assistance with roach and rodent eradication, and advocacy for improved housing conditions. Members of the low-intensity group received the initial assessment, home action plan, limited education during the assessment visit, and bedding encasements. We describe the recruitment and training of CHES and challenges they faced and explain the assessment and exposure reduction protocols addressing dust mites, mold, tobacco smoke, Pets, cockroaches, rodents, dust, moisture, and toxic or hazardous chemicals. We also discuss the gap between the practices recommended in the literature and what is feasible in the home. We accomplished home interventions and participants found the project very useful. The project was limited in resolving structural housing quality issues that contributed to exposure to indoor triggers.. asthma| children| community health workers| healthy homes| indoor environmental quality| inner city| interventions|house-dust mite| inner-city children| childhood asthma| risk-factors| urban children| tobacco-smoke| mechanical ventilation| socioeconomic-factors| allergen reduction| patient compliance.	APR-2002	asthma| children| community health workers| healthy homes| indoor environmental quality| inner city| interventions|house-dust mite| inner-city children| childhood asthma| risk-factors| urban children| tobacco-smoke| mechanical ventilation| socioeconomic-factors| allergen reduction| patient compliance	Krieger, J; Takaro, TK; Allen, C; Song, L; Weaver, M; Chai, S; Dickey, P	The Seattle-King County Healthy Homes Project: Implementation of a comprehensive approach to improving indoor environmental quality for low-income children with asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; children; community health workers; Healthy Homes; indoor environmental quality; inner city; interventions	HOUSE-DUST MITE; INNER-CITY CHILDREN; CHILDHOOD ASTHMA; RISK-FACTORS; URBAN CHILDREN; TOBACCO-SMOKE; MECHANICAL VENTILATION; SOCIOECONOMIC-FACTORS; ALLERGEN REDUCTION; PATIENT COMPLIANCE	Pediatric asthma is a growing public health issue, disproportionately affecting low-income people and people of color. Exposure to indoor asthma triggers plays an important role in the development and exacerbation of asthma. We describe the implementation of the Seattle-King County Healthy Homes Project, a randomized, controlled trial of an outreach/education intervention to improve asthma-related health status by reducing exposure to allergens and irritants in the home. We randomly assigned 274 low-income children with asthma ages 4-12 to either a high- or a low-intensity group. In the high-intensity group, community health workers called Community Home Environmental Specialists (CHES) conducted initial home environmental assessments, provided individualized action plans, and made additional visits over a 12-month period to provide education and social support, encouragement of participant actions, provision of materials to reduce exposures (including bedding encasements), assistance with roach and rodent eradication, and advocacy for improved housing conditions. Members of the low-intensity group received the initial assessment, home action plan, limited education during the assessment visit, and bedding encasements. We describe the recruitment and training of CHES and challenges they faced and explain the assessment and exposure reduction protocols addressing dust mites, mold, tobacco smoke, Pets, cockroaches, rodents, dust, moisture, and toxic or hazardous chemicals. We also discuss the gap between the practices recommended in the literature and what is feasible in the home. We accomplished home interventions and participants found the project very useful. The project was limited in resolving structural housing quality issues that contributed to exposure to indoor triggers.	142	76	2002	12		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Incidence of asthma diagnosis and self-reported allergy in relation to the school environment - a four-year follow-up study in schoolchildren. SETTING: In schools, the indoor air quality is often poor and there is growing concern about its impact on the pupils' health. OBJECTIVE: To study the incidence of asthma diagnosis and self-reported allergy in schoolchildren in relation to the school environment. DESIGN: Data on asthma and allergies were collected through a postal questionnaire answered in 1993 and 1997 by 1347 (78%) pupils (initially aged 7-13 years) in 39 randomly chosen schools. Indoor pollutants were measured in about 100 classrooms in 1993 and 1995. Relationships between indoor pollutants and incidence of asthma diagnosis and self-reported allergy were studied by multiple logistic regression, adjusting for age, sex, atopy and smoking. RESULTS: The incidence of asthma diagnosis was higher in pupils attending schools with more settled dust and more cat allergen (Fel d 1) in this dust. Incidence of self-reported furry pet allergy was higher in schools with more respirable particles. Among children without a history of atopy, a new asthma diagnosis was more common at higher concentrations of formaldehyde and total moulds in the classroom air. CONCLUSION: A school environment with more dust, cat allergen, formaldehyde and moulds may affect the incidence of asthma and sensitivity to furry pets in schoolchildren.. cat allergen| dust| formaldehyde| moulds|risk factor| northern sweden| nasal patency| cat allergen| dog can-f-1| children| dust| sensitization| classrooms| exposure.	NOV-2001	cat allergen| dust| formaldehyde| moulds|risk factor| northern sweden| nasal patency| cat allergen| dog can-f-1| children| dust| sensitization| classrooms| exposure	Smedje, G; Norback, D	Incidence of asthma diagnosis and self-reported allergy in relation to the school environment - a four-year follow-up study in schoolchildren		INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE	cat allergen; dust; formaldehyde; moulds	RISK FACTOR; NORTHERN SWEDEN; NASAL PATENCY; CAT ALLERGEN; DOG CAN-F-1; CHILDREN; DUST; SENSITIZATION; CLASSROOMS; EXPOSURE	SETTING: In schools, the indoor air quality is often poor and there is growing concern about its impact on the pupils' health. OBJECTIVE: To study the incidence of asthma diagnosis and self-reported allergy in schoolchildren in relation to the school environment. DESIGN: Data on asthma and allergies were collected through a postal questionnaire answered in 1993 and 1997 by 1347 (78%) pupils (initially aged 7-13 years) in 39 randomly chosen schools. Indoor pollutants were measured in about 100 classrooms in 1993 and 1995. Relationships between indoor pollutants and incidence of asthma diagnosis and self-reported allergy were studied by multiple logistic regression, adjusting for age, sex, atopy and smoking. RESULTS: The incidence of asthma diagnosis was higher in pupils attending schools with more settled dust and more cat allergen (Fel d 1) in this dust. Incidence of self-reported furry pet allergy was higher in schools with more respirable particles. Among children without a history of atopy, a new asthma diagnosis was more common at higher concentrations of formaldehyde and total moulds in the classroom air. CONCLUSION: A school environment with more dust, cat allergen, formaldehyde and moulds may affect the incidence of asthma and sensitivity to furry pets in schoolchildren.	35	76	2001	8		Infectious Diseases; Respiratory System
"Continuing the debate about measuring asthma in population studies. The reasons for measuring atopy and airway hyperresponsiveness (AHR) and the methods of validating measurements of asthma in population studies continue to be debated. The debate has centred around standards against which to validate asthma measurements but the absence of a ""gold standard"" makes the criterion validation of measurements difficult. Questionnaires will always be useful but cannot be validated against a doctor diagnosis because of self-selection and recall biases. In practice, measurements should be selected on the merits of what they measure rather than being regarded as validated or non-validated alternatives. The measurement of AHR is invaluable because it is reliable, not influenced by variations in symptom perception or diagnostic trends, and is closely related to the underlying mechanisms of asthma. The value of AHR lies in its high specificity (rate of true negatives) and low sensitivity (rate of false positives) against asthma symptoms which gives additional information about symptomatic subjects. Atopy is also a useful test and, in quantifying its association with asthma, we should not place any currency on ecological evidence. Atopy is a strong risk factor for asthma in the presence of regionally specific allergens and ecological analyses that ignore these effects are diversionary rather than productive. For preventing asthma, we need to identify the group at greatest risk of developing it, measure the risk factors with precision, and develop interventions that are effective in changing environmental exposures and homogenous outcomes. This is the only approach that has the potential to lead to significant public health benefits.. asthma| atopy| population studies|house-dust mite| new-south-wales| allergic disorders| childhood asthma| bronchial responsiveness| climatic regions| children| prevalence| atopy| sensitization."	MAY-2001	asthma| atopy| population studies|house-dust mite| new-south-wales| allergic disorders| childhood asthma| bronchial responsiveness| climatic regions| children| prevalence| atopy| sensitization	Peat, JK; Toelle, BG; Marks, GB; Mellis, CM	Continuing the debate about measuring asthma in population studies		THORAX	asthma; atopy; population studies	HOUSE-DUST MITE; NEW-SOUTH-WALES; ALLERGIC DISORDERS; CHILDHOOD ASTHMA; BRONCHIAL RESPONSIVENESS; CLIMATIC REGIONS; CHILDREN; PREVALENCE; ATOPY; SENSITIZATION	"The reasons for measuring atopy and airway hyperresponsiveness (AHR) and the methods of validating measurements of asthma in population studies continue to be debated. The debate has centred around standards against which to validate asthma measurements but the absence of a ""gold standard"" makes the criterion validation of measurements difficult. Questionnaires will always be useful but cannot be validated against a doctor diagnosis because of self-selection and recall biases. In practice, measurements should be selected on the merits of what they measure rather than being regarded as validated or non-validated alternatives. The measurement of AHR is invaluable because it is reliable, not influenced by variations in symptom perception or diagnostic trends, and is closely related to the underlying mechanisms of asthma. The value of AHR lies in its high specificity (rate of true negatives) and low sensitivity (rate of false positives) against asthma symptoms which gives additional information about symptomatic subjects. Atopy is also a useful test and, in quantifying its association with asthma, we should not place any currency on ecological evidence. Atopy is a strong risk factor for asthma in the presence of regionally specific allergens and ecological analyses that ignore these effects are diversionary rather than productive. For preventing asthma, we need to identify the group at greatest risk of developing it, measure the risk factors with precision, and develop interventions that are effective in changing environmental exposures and homogenous outcomes. This is the only approach that has the potential to lead to significant public health benefits."	29	76	2001	6	10.1136/thorax.56.5.406	Respiratory System
A springtime Olympics demands special consideration for allergic athletes. Background: The Sydney Olympic and Paralympic Games will be held in September-October 2000, which is early to midspring in the southern hemisphere. Pollen-sensitive athletes may encounter problems with allergic symptoms triggered by pollen exposure, thus compromising their ability to attain peak performance. Objective: We sought to monitor pollen levels at the major Olympic venues to provide information for allergic athletes and their team doctors in order to adequately prepare them for Olympic competition. Methods: We performed aerobiologic monitoring of the major Olympic venues to provide a profile of the most prevalent pollen species appearing during the spring. In the second part of this study, we surveyed a population of elite Australian athletes from Olympic sports to ascertain the prevalence of allergic rhinoconjunctivitis, to investigate the major allergens involved in sensitization, and to conduct a pilot study to assess the effect of allergic rhinoconjunctivitis on quality of life. Results: The pollen counts obtained at the 3 major sites were high over the period of Olympic competition. Tree pollens appeared from July, and grasses appeared from early September and peaked in the second week of October, the beginning of Paralympic competition. A relatively small number of pollen varieties comprise the majority of the total pollen count. Two hundred fourteen athletes (61% male; mean age, 21 +/- 16 years) representing 12 Olympic sports participated in the study. Fifty-six percent gave a symptom history consistent with allergic rhinoconjunctivitis, 41% had symptoms of allergic rhinoconjunctivitis and a positive test response to any one allergen, and 29% had seasonal allergic rhinoconjunctivitis (a positive history and at least one positive skin prick test response to a seasonal allergen). Athletes from aquatic sports were more likely to have symptoms than those from other sports, Symptom scores were higher and quality of life ratings were poorer in allergic compared with nonallergic athletes over the spring period, Conclusion: Olympic team managers and medical officers need to adequately prepare Olympic athletes for the possibility of exposure to high pollen levels in the weeks leading up to this most important sporting event. Symptoms of pollen sensitivity, such as rhinoconjunctivitis and exacerbation of asthma, could be devastating to athletes expecting peak performance, Potential Olympic athletes should be screened for the possibility of pollen allergy and have medical programs with permitted medication tailored to meet their needs. This may involve preventative therapy with meditation, such as intranasal corticosteroid sprays or immunotherapy programs, if symptoms are particularly severe. The newer nonsedating antihistamines are the treatment of choice fur acute intermittent symptoms, Appropriate management will ensure that the allergic athlete will safely perform to maximum ability with permitted medication during the Spring 2000 Olympic Games in Sydney.. pollen counts| athletes| allergic rhinoconjunctivitis| olympics| paralympics| asthma|quality-of-life| hay-fever| questionnaire| asthma.	AUG-2000	pollen counts| athletes| allergic rhinoconjunctivitis| olympics| paralympics| asthma|quality-of-life| hay-fever| questionnaire| asthma	Katelaris, CH; Carrozzi, FM; Burke, TV; Byth, K	A springtime Olympics demands special consideration for allergic athletes		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	pollen counts; athletes; allergic rhinoconjunctivitis; olympics; paralympics; asthma	QUALITY-OF-LIFE; HAY-FEVER; QUESTIONNAIRE; ASTHMA	Background: The Sydney Olympic and Paralympic Games will be held in September-October 2000, which is early to midspring in the southern hemisphere. Pollen-sensitive athletes may encounter problems with allergic symptoms triggered by pollen exposure, thus compromising their ability to attain peak performance. Objective: We sought to monitor pollen levels at the major Olympic venues to provide information for allergic athletes and their team doctors in order to adequately prepare them for Olympic competition. Methods: We performed aerobiologic monitoring of the major Olympic venues to provide a profile of the most prevalent pollen species appearing during the spring. In the second part of this study, we surveyed a population of elite Australian athletes from Olympic sports to ascertain the prevalence of allergic rhinoconjunctivitis, to investigate the major allergens involved in sensitization, and to conduct a pilot study to assess the effect of allergic rhinoconjunctivitis on quality of life. Results: The pollen counts obtained at the 3 major sites were high over the period of Olympic competition. Tree pollens appeared from July, and grasses appeared from early September and peaked in the second week of October, the beginning of Paralympic competition. A relatively small number of pollen varieties comprise the majority of the total pollen count. Two hundred fourteen athletes (61% male; mean age, 21 +/- 16 years) representing 12 Olympic sports participated in the study. Fifty-six percent gave a symptom history consistent with allergic rhinoconjunctivitis, 41% had symptoms of allergic rhinoconjunctivitis and a positive test response to any one allergen, and 29% had seasonal allergic rhinoconjunctivitis (a positive history and at least one positive skin prick test response to a seasonal allergen). Athletes from aquatic sports were more likely to have symptoms than those from other sports, Symptom scores were higher and quality of life ratings were poorer in allergic compared with nonallergic athletes over the spring period, Conclusion: Olympic team managers and medical officers need to adequately prepare Olympic athletes for the possibility of exposure to high pollen levels in the weeks leading up to this most important sporting event. Symptoms of pollen sensitivity, such as rhinoconjunctivitis and exacerbation of asthma, could be devastating to athletes expecting peak performance, Potential Olympic athletes should be screened for the possibility of pollen allergy and have medical programs with permitted medication tailored to meet their needs. This may involve preventative therapy with meditation, such as intranasal corticosteroid sprays or immunotherapy programs, if symptoms are particularly severe. The newer nonsedating antihistamines are the treatment of choice fur acute intermittent symptoms, Appropriate management will ensure that the allergic athlete will safely perform to maximum ability with permitted medication during the Spring 2000 Olympic Games in Sydney.	12	76	2000	7		Allergy; Immunology
C-type lectins in immunity: recent developments. C-type lectin receptors (CLRs) comprise a large superfamily of proteins, which recognise a diverse range of ligands, and are defined by the presence of at least one C-type lectin-like domain (CTLD). Of particular interest are the single extracellular CTLD-containing receptors of the 'Dectin-1' and 'Dectin-2' clusters, which associate with signalling adaptors or possess integral intracellular signalling domains. These CLRs have traditionally been associated with the recognition of fungi, but recent discoveries have revealed diverse and unexpected functions. In this review, we describe their newly identified roles in anti-microbial host defence, homeostasis, autoimmunity, allergy and their functions in the recognition and response to dead and cancerous cells.. house-dust mite| dendritic cell-receptor| fungal beta-glucans| candida-albicans| host-defense| airway inflammation| antifungal immunity| innate immunity| damaged cells| cord factor.	FEB-2015	house-dust mite| dendritic cell-receptor| fungal beta-glucans| candida-albicans| host-defense| airway inflammation| antifungal immunity| innate immunity| damaged cells| cord factor	Dambuza, IM; Brown, GD	C-type lectins in immunity: recent developments		CURRENT OPINION IN IMMUNOLOGY		HOUSE-DUST MITE; DENDRITIC CELL-RECEPTOR; FUNGAL BETA-GLUCANS; CANDIDA-ALBICANS; HOST-DEFENSE; AIRWAY INFLAMMATION; ANTIFUNGAL IMMUNITY; INNATE IMMUNITY; DAMAGED CELLS; CORD FACTOR	C-type lectin receptors (CLRs) comprise a large superfamily of proteins, which recognise a diverse range of ligands, and are defined by the presence of at least one C-type lectin-like domain (CTLD). Of particular interest are the single extracellular CTLD-containing receptors of the 'Dectin-1' and 'Dectin-2' clusters, which associate with signalling adaptors or possess integral intracellular signalling domains. These CLRs have traditionally been associated with the recognition of fungi, but recent discoveries have revealed diverse and unexpected functions. In this review, we describe their newly identified roles in anti-microbial host defence, homeostasis, autoimmunity, allergy and their functions in the recognition and response to dead and cancerous cells.	73	75	2015	7	10.1016/j.coi.2014.12.002	Immunology
"Health care use and serious infection prevalence associated with penicillin ""allergy"" in hospitalized patients: A cohort study. Background: Penicillin is the most common drug ""allergy"" noted at hospital admission, although it is often inaccurate. Objective: We sought to determine total hospital days, antibiotic exposures, and the prevalence rates of Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) in patients with and without penicillin ""allergy"" at hospital admission. Methods: We performed a retrospective, matched cohort study of subjects admitted to Kaiser Foundation hospitals in Southern California during 2010 through 2012. Results: It was possible to match 51,582 (99.6% of all possible cases) unique hospitalized subjects with penicillin ""allergy"" to 2 unique discharge diagnosis category-matched, sex-matched, age-matched, and date of admission-matched control subjects each. Cases with penicillin ""allergy"" averaged 0.59 (9.9%; 95% CI, 0.47-0.71) more total hospital days during 20.1 +/- 10.5 months of follow-up compared with control subjects. Cases were treated with significantly more fluoroquinolones, clindamycin, and vancomycin (P < .0001) for each antibiotic compared with control subjects. Cases had 23.4% (95% CI, 15.6% to 31.7%) more C difficile, 14.1% (95% CI, 7.1% to 21.6%) more MRSA, and 30.1% (95% CI, 12.5% to 50.4%) more VRE infections than expected compared with control subjects. Conclusions: A penicillin ""allergy"" history, although often inaccurate, is not a benign finding at hospital admission. Subjects with a penicillin ""allergy"" history spend significantly more time in the hospital. Subjects with a penicillin ""allergy"" history are exposed to significantly more antibiotics previously associated with C difficile and VRE. Drug ""allergies"" in general, but most those notably to penicillin, are associated with increased hospital use and increased C difficile, MRSA, and VRE prevalence.. adverse drug reaction| antibiotics| clostridium difficile| electronic medical record| hospital use| methicillin-resistant staphylococcus aureus| multiple drug intolerance syndrome| penicillin allergy| prevalence| vancomycin-resistant enterococcus species|group-b streptococcus| clostridium-difficile| antimicrobial stewardship| pregnant-women| vancomycin use| history| management| antibiotics| costs."	MAR-2014	adverse drug reaction| antibiotics| clostridium difficile| electronic medical record| hospital use| methicillin-resistant staphylococcus aureus| multiple drug intolerance syndrome| penicillin allergy| prevalence| vancomycin-resistant enterococcus species|group-b streptococcus| clostridium-difficile| antimicrobial stewardship| pregnant-women| vancomycin use| history| management| antibiotics| costs	Macy, E; Contreras, R	"Health care use and serious infection prevalence associated with penicillin ""allergy"" in hospitalized patients: A cohort study"		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Adverse drug reaction; antibiotics; Clostridium difficile; electronic medical record; hospital use; methicillin-resistant Staphylococcus aureus; multiple drug intolerance syndrome; penicillin allergy; prevalence; vancomycin-resistant Enterococcus species	GROUP-B STREPTOCOCCUS; CLOSTRIDIUM-DIFFICILE; ANTIMICROBIAL STEWARDSHIP; PREGNANT-WOMEN; VANCOMYCIN USE; HISTORY; MANAGEMENT; ANTIBIOTICS; COSTS	"Background: Penicillin is the most common drug ""allergy"" noted at hospital admission, although it is often inaccurate. Objective: We sought to determine total hospital days, antibiotic exposures, and the prevalence rates of Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) in patients with and without penicillin ""allergy"" at hospital admission. Methods: We performed a retrospective, matched cohort study of subjects admitted to Kaiser Foundation hospitals in Southern California during 2010 through 2012. Results: It was possible to match 51,582 (99.6% of all possible cases) unique hospitalized subjects with penicillin ""allergy"" to 2 unique discharge diagnosis category-matched, sex-matched, age-matched, and date of admission-matched control subjects each. Cases with penicillin ""allergy"" averaged 0.59 (9.9%; 95% CI, 0.47-0.71) more total hospital days during 20.1 +/- 10.5 months of follow-up compared with control subjects. Cases were treated with significantly more fluoroquinolones, clindamycin, and vancomycin (P < .0001) for each antibiotic compared with control subjects. Cases had 23.4% (95% CI, 15.6% to 31.7%) more C difficile, 14.1% (95% CI, 7.1% to 21.6%) more MRSA, and 30.1% (95% CI, 12.5% to 50.4%) more VRE infections than expected compared with control subjects. Conclusions: A penicillin ""allergy"" history, although often inaccurate, is not a benign finding at hospital admission. Subjects with a penicillin ""allergy"" history spend significantly more time in the hospital. Subjects with a penicillin ""allergy"" history are exposed to significantly more antibiotics previously associated with C difficile and VRE. Drug ""allergies"" in general, but most those notably to penicillin, are associated with increased hospital use and increased C difficile, MRSA, and VRE prevalence."	33	75	2014	7	10.1016/j.jaci.2013.09.021	Allergy; Immunology
Infant origins of childhood asthma associated with specific molds. Background: The specific cause or causes of asthma development must be identified to prevent this disease. Objective: Our hypothesis was that specific mold exposures are associated with childhood asthma development. Methods: Infants were identified from birth certificates. Dust samples were collected from 289 homes when the infants were 8 months of age. Samples were analyzed for concentrations of 36 molds that comprise the Environmental Relative Moldiness Index (ERMI) and endotoxin, house dust mite, cat, dog, and cockroach allergens. Children were evaluated at age 7 years for asthma based on reported symptoms and objective measures of lung function. Host, environmental exposure, and home characteristics evaluated included a history of parental asthma, race, sex, upper and lower respiratory tract symptoms, season of birth, family income, cigarette smoke exposure, air conditioning, use of a dehumidifier, presence of carpeting, age of home, and visible mold at age 1 year and child's positive skin prick test response to aeroallergens and molds at age 7 years. Results: Asthma was diagnosed in 24% of the children at age 7 years. A statistically significant increase in asthma risk at age 7 years was associated with high ERMI values in the child's home in infancy (adjusted relative risk for a 10-unit increase in ERMI value, 1.8; 95% CI, 1.5-2.2). The summation of levels of 3 mold species, Aspergillus ochraceus, Aspergillus unguis, and Penicillium variabile, was significantly associated with asthma (adjusted relative risk, 2.2; 95% CI, 1.8-2.7). Conclusion: In this birth cohort study exposure during infancy to 3 mold species common to water-damaged buildings was associated with childhood asthma at age 7 years. (J Allergy Clin Immunol 2012;130:639-44.). asthma| molds| speciation| infants| environmental relative moldiness index|quantitative pcr analysis| relative moldiness index| 1st year| alternaria-alternata| house-dust| us homes| children| cohort| symptoms| exposure.	SEP-2012	asthma| molds| speciation| infants| environmental relative moldiness index|quantitative pcr analysis| relative moldiness index| 1st year| alternaria-alternata| house-dust| us homes| children| cohort| symptoms| exposure	Reponen, T; Lockey, J; Bernstein, DI; Vesper, SJ; Levin, L; Hershey, GKK; Zheng, S; Ryan, P; Grinshpun, SA; Villareal, M; LeMasters, G	Infant origins of childhood asthma associated with specific molds		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Asthma; molds; speciation; infants; Environmental Relative Moldiness Index	QUANTITATIVE PCR ANALYSIS; RELATIVE MOLDINESS INDEX; 1ST YEAR; ALTERNARIA-ALTERNATA; HOUSE-DUST; US HOMES; CHILDREN; COHORT; SYMPTOMS; EXPOSURE	Background: The specific cause or causes of asthma development must be identified to prevent this disease. Objective: Our hypothesis was that specific mold exposures are associated with childhood asthma development. Methods: Infants were identified from birth certificates. Dust samples were collected from 289 homes when the infants were 8 months of age. Samples were analyzed for concentrations of 36 molds that comprise the Environmental Relative Moldiness Index (ERMI) and endotoxin, house dust mite, cat, dog, and cockroach allergens. Children were evaluated at age 7 years for asthma based on reported symptoms and objective measures of lung function. Host, environmental exposure, and home characteristics evaluated included a history of parental asthma, race, sex, upper and lower respiratory tract symptoms, season of birth, family income, cigarette smoke exposure, air conditioning, use of a dehumidifier, presence of carpeting, age of home, and visible mold at age 1 year and child's positive skin prick test response to aeroallergens and molds at age 7 years. Results: Asthma was diagnosed in 24% of the children at age 7 years. A statistically significant increase in asthma risk at age 7 years was associated with high ERMI values in the child's home in infancy (adjusted relative risk for a 10-unit increase in ERMI value, 1.8; 95% CI, 1.5-2.2). The summation of levels of 3 mold species, Aspergillus ochraceus, Aspergillus unguis, and Penicillium variabile, was significantly associated with asthma (adjusted relative risk, 2.2; 95% CI, 1.8-2.7). Conclusion: In this birth cohort study exposure during infancy to 3 mold species common to water-damaged buildings was associated with childhood asthma at age 7 years. (J Allergy Clin Immunol 2012;130:639-44.)	44	75	2012	11	10.1016/j.jaci.2012.05.030	Allergy; Immunology
Intrinsic Phenotypic Differences of Asthmatic Epithelium and Its Inflammatory Responses to Respiratory Syncytial Virus and Air Pollution. A substantial proportion of healthcare cost associated with asthma is attributable to exacerbations of the disease. Within the airway, the epithelium forms the mucosal immune barrier, the first structural cell defense against common environmental insults such as respiratory syncytial virus (RSV) and particulate matter. We sought to characterize the phenotype of differentiated asthmatic-derived airway epithelial cultures and their intrinsic inflammatory responses to environmental challenges. Air-liquid interface (ALI) cultures were generated from asthmatic (n = 6) and nonasthmatic (n = 6) airway epithelial cells. Airway tissue and ALI cultures were analyzed by immunohistochemistry for cytokeratin-5, E-cadherin, Ki67, Muc5AC, NF-kappa B, the activation of p38, and apoptosis. ALI cultures were exposed to RSV (4 x 10(6) plaque forming unit/ml), particulate matter collected by Environmental Health Canada (EHC-93, 100 mu g/ml), or mechanically wounded for 24, 48, and 96 hours and basolateral supernatants analyzed for inflammatory cytokines, using Luminex and ELISA. The airway epithelium in airway sections of patients with asthma as well as in vitro ALI cultures demonstrated a less differentiated epithelium, characterized by elevated numbers of basal cells marked by the expression of cytokeratin-5, increased phosphorylation of p38 mitogen-activated protein kinase, and less adherens junction protein E-cadherin. Transepithelial resistance was not different between asthmatic and nonasthmatic cultures. In response to infection with RSV, exposure to EHC-93, or mechanical wounding, asthmatic ALI cultures released greater concentrations of IL-6, IL-8, and granulocyte macrophage colony-stimulating factor, compared with nonasthmatic cultures (P < 0.05). This parallel ex vivo and in vitro study of the asthmatic epithelium demonstrates an intrinsically altered phenotype and aberrant inflammatory response to common environmental challenges, compared with nonasthmatic epithelium.. airway epithelium| asthma| inflammation and repair| rsv| particulate matter|epidermal-growth-factor| activated protein-kinases| fine particulate matter| bronchial epithelium| cytokine production| factor receptor| alveolar macrophages| dysregulated repair| signal transducer| mapk activation.	NOV-2011	airway epithelium| asthma| inflammation and repair| rsv| particulate matter|epidermal-growth-factor| activated protein-kinases| fine particulate matter| bronchial epithelium| cytokine production| factor receptor| alveolar macrophages| dysregulated repair| signal transducer| mapk activation	Hackett, TL; Singhera, GK; Shaheen, F; Hayden, P; Jackson, GR; Hegele, RG; Van Eeden, S; Bai, TR; Dorscheid, DR; Knight, DA	Intrinsic Phenotypic Differences of Asthmatic Epithelium and Its Inflammatory Responses to Respiratory Syncytial Virus and Air Pollution		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	airway epithelium; asthma; inflammation and repair; RSV; particulate matter	EPIDERMAL-GROWTH-FACTOR; ACTIVATED PROTEIN-KINASES; FINE PARTICULATE MATTER; BRONCHIAL EPITHELIUM; CYTOKINE PRODUCTION; FACTOR RECEPTOR; ALVEOLAR MACROPHAGES; DYSREGULATED REPAIR; SIGNAL TRANSDUCER; MAPK ACTIVATION	A substantial proportion of healthcare cost associated with asthma is attributable to exacerbations of the disease. Within the airway, the epithelium forms the mucosal immune barrier, the first structural cell defense against common environmental insults such as respiratory syncytial virus (RSV) and particulate matter. We sought to characterize the phenotype of differentiated asthmatic-derived airway epithelial cultures and their intrinsic inflammatory responses to environmental challenges. Air-liquid interface (ALI) cultures were generated from asthmatic (n = 6) and nonasthmatic (n = 6) airway epithelial cells. Airway tissue and ALI cultures were analyzed by immunohistochemistry for cytokeratin-5, E-cadherin, Ki67, Muc5AC, NF-kappa B, the activation of p38, and apoptosis. ALI cultures were exposed to RSV (4 x 10(6) plaque forming unit/ml), particulate matter collected by Environmental Health Canada (EHC-93, 100 mu g/ml), or mechanically wounded for 24, 48, and 96 hours and basolateral supernatants analyzed for inflammatory cytokines, using Luminex and ELISA. The airway epithelium in airway sections of patients with asthma as well as in vitro ALI cultures demonstrated a less differentiated epithelium, characterized by elevated numbers of basal cells marked by the expression of cytokeratin-5, increased phosphorylation of p38 mitogen-activated protein kinase, and less adherens junction protein E-cadherin. Transepithelial resistance was not different between asthmatic and nonasthmatic cultures. In response to infection with RSV, exposure to EHC-93, or mechanical wounding, asthmatic ALI cultures released greater concentrations of IL-6, IL-8, and granulocyte macrophage colony-stimulating factor, compared with nonasthmatic cultures (P < 0.05). This parallel ex vivo and in vitro study of the asthmatic epithelium demonstrates an intrinsically altered phenotype and aberrant inflammatory response to common environmental challenges, compared with nonasthmatic epithelium.	80	75	2011	11	10.1165/rcmb.2011-0031OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Colloidal aspects of protein digestion. The increase in food related health issues has sparked an interest in research on the digestion processes of the gastrointestinal tract. Because of the difficulty and expense of undertaking human trials or even animal experiments, much of the current research uses in vitro models that simulate various aspects of digestion. The results of this research indicate that the rate and extent of protein digestion is governed by accessibility of the cleavage sites to enzymes and local flexibility of the substrate molecule. However, results have also shown that digestion of an allergenic protein to small fragments does not necessarily mean that it will no longer be immunologically active. Other factors are also important. For example, adsorption to an interface increased rates of digestion as did the presence of bile acids. In fact, interaction with a range of physiological surfactants has been shown to be extremely important in protein digestion. When protein is adsorbed to an emulsified food it can be displaced by the surfactants in either the stomach or the small intestine. Lipid interaction with the protein in solution has been demonstrated to be important in effecting rates of proteolysis and phospholipids in particular have provided a protective effect for some milk proteins. Conversely the presence of specific proteins has been shown to affect rates of lipid digestion. The number of such colloidal interactions that we now know may play a role in protein digestion highlights the importance of this area to understanding how we can produce food that optimises nutrition for the consumer. (C) 2009 Elsevier Ltd. All rights reserved.. interface| protein| digestion| biosurfactant| enzyme| emulsion|in-vitro digestibility| simulated gastrointestinal proteolysis| intragastric acid stability| air-water-interface| beta-lactoglobulin| food allergens| enzymatic-hydrolysis| pancreatic lipase| emulsifier type| bile-acids.	APR-2010	interface| protein| digestion| biosurfactant| enzyme| emulsion|in-vitro digestibility| simulated gastrointestinal proteolysis| intragastric acid stability| air-water-interface| beta-lactoglobulin| food allergens| enzymatic-hydrolysis| pancreatic lipase| emulsifier type| bile-acids	Mackie, A; Macierzanka, A	Colloidal aspects of protein digestion		CURRENT OPINION IN COLLOID & INTERFACE SCIENCE	Interface; Protein; Digestion; Biosurfactant; Enzyme; Emulsion	IN-VITRO DIGESTIBILITY; SIMULATED GASTROINTESTINAL PROTEOLYSIS; INTRAGASTRIC ACID STABILITY; AIR-WATER-INTERFACE; BETA-LACTOGLOBULIN; FOOD ALLERGENS; ENZYMATIC-HYDROLYSIS; PANCREATIC LIPASE; EMULSIFIER TYPE; BILE-ACIDS	The increase in food related health issues has sparked an interest in research on the digestion processes of the gastrointestinal tract. Because of the difficulty and expense of undertaking human trials or even animal experiments, much of the current research uses in vitro models that simulate various aspects of digestion. The results of this research indicate that the rate and extent of protein digestion is governed by accessibility of the cleavage sites to enzymes and local flexibility of the substrate molecule. However, results have also shown that digestion of an allergenic protein to small fragments does not necessarily mean that it will no longer be immunologically active. Other factors are also important. For example, adsorption to an interface increased rates of digestion as did the presence of bile acids. In fact, interaction with a range of physiological surfactants has been shown to be extremely important in protein digestion. When protein is adsorbed to an emulsified food it can be displaced by the surfactants in either the stomach or the small intestine. Lipid interaction with the protein in solution has been demonstrated to be important in effecting rates of proteolysis and phospholipids in particular have provided a protective effect for some milk proteins. Conversely the presence of specific proteins has been shown to affect rates of lipid digestion. The number of such colloidal interactions that we now know may play a role in protein digestion highlights the importance of this area to understanding how we can produce food that optimises nutrition for the consumer. (C) 2009 Elsevier Ltd. All rights reserved.	54	75	2010	7	10.1016/j.cocis.2009.11.005	Chemistry
Obesity, airway hyperresponsiveness, and inflammation. Shore SA. Obesity, airway hyperresponsiveness, and inflammation. J Appl Physiol 108: 735-743, 2010. First published October 29, 2009; doi: 10.1152/japplphysiol.00749.2009.-Epidemiological data indicate that obesity is a risk factor for asthma, but the mechanistic basis for this relationship is not established. Here we review data from human subjects and animal models investigating the relationship between obesity and airway hyperresponsiveness, a characteristic feature of asthma. We discuss obesity as a state of chronic systemic inflammation resulting from interactions between adipocytes and adipose tissue macrophages that are recruited to obese adipose tissue. Finally, we focus on the possibility that aspects of this inflammation, particularly obesity-related changes in TNF-alpha, leptin, and adiponectin, may contribute to airway hyperresponsiveness in obesity. Determining how obesity promotes asthma may uncover novel therapeutic strategies that are effective in the obese asthmatic subject.. mice| leptin| adiponectin| tumor necrosis factor-alpha| adipokines|body-mass index| adipose-tissue hypoxia| necrosis-factor-alpha| diet-induced obesity| exercise-induced bronchospasm| induced insulin-resistance| acute ozone exposure| murine asthma model| high-fat diet| pulmonary-function.	MAR-2010	mice| leptin| adiponectin| tumor necrosis factor-alpha| adipokines|body-mass index| adipose-tissue hypoxia| necrosis-factor-alpha| diet-induced obesity| exercise-induced bronchospasm| induced insulin-resistance| acute ozone exposure| murine asthma model| high-fat diet| pulmonary-function	Shore, SA	Obesity, airway hyperresponsiveness, and inflammation		JOURNAL OF APPLIED PHYSIOLOGY	mice; leptin; adiponectin; tumor necrosis factor-alpha; adipokines	BODY-MASS INDEX; ADIPOSE-TISSUE HYPOXIA; NECROSIS-FACTOR-ALPHA; DIET-INDUCED OBESITY; EXERCISE-INDUCED BRONCHOSPASM; INDUCED INSULIN-RESISTANCE; ACUTE OZONE EXPOSURE; MURINE ASTHMA MODEL; HIGH-FAT DIET; PULMONARY-FUNCTION	Shore SA. Obesity, airway hyperresponsiveness, and inflammation. J Appl Physiol 108: 735-743, 2010. First published October 29, 2009; doi: 10.1152/japplphysiol.00749.2009.-Epidemiological data indicate that obesity is a risk factor for asthma, but the mechanistic basis for this relationship is not established. Here we review data from human subjects and animal models investigating the relationship between obesity and airway hyperresponsiveness, a characteristic feature of asthma. We discuss obesity as a state of chronic systemic inflammation resulting from interactions between adipocytes and adipose tissue macrophages that are recruited to obese adipose tissue. Finally, we focus on the possibility that aspects of this inflammation, particularly obesity-related changes in TNF-alpha, leptin, and adiponectin, may contribute to airway hyperresponsiveness in obesity. Determining how obesity promotes asthma may uncover novel therapeutic strategies that are effective in the obese asthmatic subject.	108	75	2010	9	10.1152/japplphysiol.00749.2009	Physiology; Sport Sciences
"The spatial relationship between traffic-generated air pollution and noise in 2 US cities. Traffic-gene rated air pollution and noise have both been linked to cardiovascular morbidity. Since traffic is a shared source, there is potential for correlated exposures that may lead to confounding in epidemiologic studies. As part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), 2-week NO and NO(2) concentrations were measured at up to 105 locations, selected primarily to characterize gradients near major roads, in each of 9 US communities. We measured 5-min A-weighted equivalent continuous sound pressure levels (L(eq)) and ultrafine particle (UFP) counts at a subset of these NO/NO(2) monitoring locations in Chicago, IL (N = 69 in December 2006; N = 36 in April 2007) and Riverside County, CA (N = 46 in April 2007). L(eq) and UFP were measured during non-""rush hour"" periods (10:00-16:00) to maximize comparability between measurements. We evaluated roadway proximity exposure surrogates in relation to the measured levels, estimated noise-air pollution correlation coefficients, and evaluated the impact of regional-scale pollution gradients, wind direction, and roadway proximity on the correlations. Five-minute L(eq) measurements in December 2006 and April 2007 were highly correlated (r = 0.84), and measurements made at different times of day were similar (coefficients of variation: 0.5-13%), indicating that 5-min measurements are representative of long-term L(eq), Binary and continuous roadway proximity metrics characterized L(eq) as well or better than NO or NO(2). We found strong regional-scale gradients in NO and NO(2), particularly in Chicago, but only weak regional-scale gradients in L(eq) and UFP. L(eq) was most consistently correlated with NO, but the correlations were moderate (0.20-0.60). After removing the influence of regional-scale gradients the correlations generally increased (L(eq)-NO: r = 0.49-0.62), and correlations downwind of major roads (L(eq)-NO: r = 0.53-0.74) were consistently higher than those upwind (0.35-0.65). There was not a consistent effect of roadway proximity on the correlations. In conclusion, roadway proximity variables are not unique exposure surrogates in studies of endpoints hypothesized to be related to both air pollution and noise. Moderate correlations between traffic-generated air pollution and noise suggest the possibility of confounding, which might be minimized by considering regional pollution gradients and/or prevailing wind direction(s) in epidemiologic studies. (C) 2009 Elsevier Inc. All rights reserved.. air pollution| noise| traffic| confounding| cardiovascular|ambient nitrogen-dioxide| major highway| myocardial-infarction| ultrafine particles| heart-disease| los-angeles| exposure| asthma| mortality| association."	APR-2009	air pollution| noise| traffic| confounding| cardiovascular|ambient nitrogen-dioxide| major highway| myocardial-infarction| ultrafine particles| heart-disease| los-angeles| exposure| asthma| mortality| association	Allen, RW; Davies, H; Cohen, MA; Mallach, G; Kaufman, JD; Adar, SD	The spatial relationship between traffic-generated air pollution and noise in 2 US cities		ENVIRONMENTAL RESEARCH	Air pollution; Noise; Traffic; Confounding; Cardiovascular	AMBIENT NITROGEN-DIOXIDE; MAJOR HIGHWAY; MYOCARDIAL-INFARCTION; ULTRAFINE PARTICLES; HEART-DISEASE; LOS-ANGELES; EXPOSURE; ASTHMA; MORTALITY; ASSOCIATION	"Traffic-gene rated air pollution and noise have both been linked to cardiovascular morbidity. Since traffic is a shared source, there is potential for correlated exposures that may lead to confounding in epidemiologic studies. As part of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), 2-week NO and NO(2) concentrations were measured at up to 105 locations, selected primarily to characterize gradients near major roads, in each of 9 US communities. We measured 5-min A-weighted equivalent continuous sound pressure levels (L(eq)) and ultrafine particle (UFP) counts at a subset of these NO/NO(2) monitoring locations in Chicago, IL (N = 69 in December 2006; N = 36 in April 2007) and Riverside County, CA (N = 46 in April 2007). L(eq) and UFP were measured during non-""rush hour"" periods (10:00-16:00) to maximize comparability between measurements. We evaluated roadway proximity exposure surrogates in relation to the measured levels, estimated noise-air pollution correlation coefficients, and evaluated the impact of regional-scale pollution gradients, wind direction, and roadway proximity on the correlations. Five-minute L(eq) measurements in December 2006 and April 2007 were highly correlated (r = 0.84), and measurements made at different times of day were similar (coefficients of variation: 0.5-13%), indicating that 5-min measurements are representative of long-term L(eq), Binary and continuous roadway proximity metrics characterized L(eq) as well or better than NO or NO(2). We found strong regional-scale gradients in NO and NO(2), particularly in Chicago, but only weak regional-scale gradients in L(eq) and UFP. L(eq) was most consistently correlated with NO, but the correlations were moderate (0.20-0.60). After removing the influence of regional-scale gradients the correlations generally increased (L(eq)-NO: r = 0.49-0.62), and correlations downwind of major roads (L(eq)-NO: r = 0.53-0.74) were consistently higher than those upwind (0.35-0.65). There was not a consistent effect of roadway proximity on the correlations. In conclusion, roadway proximity variables are not unique exposure surrogates in studies of endpoints hypothesized to be related to both air pollution and noise. Moderate correlations between traffic-generated air pollution and noise suggest the possibility of confounding, which might be minimized by considering regional pollution gradients and/or prevailing wind direction(s) in epidemiologic studies. (C) 2009 Elsevier Inc. All rights reserved."	46	75	2009	9	10.1016/j.envres.2008.12.006	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Patterns of Drug Use and Factors Associated with Polypharmacy and Excessive Polypharmacy in Elderly Persons Results of the Kuopio 75+Study: A Cross-Sectional Analysis. Background: Although the increasing use of drugs in elderly persons has raised many concerns in recent years, the process leading to polypharmacy (PP) and excessive polypharmacy (EPP) remains largely unknown. Objective: To describe the number and type of drugs used and to evaluate the role of different factors associated with PP (i.e. 6-9 drugs) and EPP (i.e. >= 10 drugs), with special reference to the number and type of medical diagnoses and symptoms, in a population of home-dwelling elderly persons aged >= 75 years. Methods: The study was a cross-sectional analysis of a population-based cohort in 1998. The population consisted of home-dwelling elderly persons aged >= 75 years in the city of Kuopio, Finland. The data for the analysis were obtained from the Kuopio 75+ Study, which drew a random sample of 700 elderly residents aged >= 75 years living in the city of Kuopio from the population register. Of these, 601 attended a structured clinical examination and an interview carried out by a geriatrician and a trained nurse in 1998. For this analysis, all home-dwelling elderly participants (n=523) were included. Study data were expressed as proportions and means with standard deviations. The factors associated with PP and EPP were examined by multinomial logistic regression. Results: The most commonly used drugs were cardiovascular drugs (97% in EPP, 94% in PP and 59% in non-PP group) and analgesics (89%, 76% and 54%), respectively. Use of psychotropics was markedly higher in the EPP group (77%) than in the PP (42%) and non-PP groups (20%). The mean number of drugs per diagnosis was 3.6 in the EPP group, 2.6 in the PP group and 1.6 in the non-PP group. Factors associated only with EPP were moderate self-reported health (odds ratio [OR] 2.05; 95% CI 1.08, 3.89), female gender (OR 2.43; 95% CI 1.27, 4.65) and age >= 85 years (OR 2.84; 95% CI 1.41, 5.72). Factors that were associated with both PP and EPP included poor self-reported health (PP: OR 2.15; 95% CI 1.01, 4.59 and EPP: OR 6.02; 95% CI 2.55, 14.20), diabetes mellitus (PP: OR 2.28; 95% CI 1.26, 4.15 and EPP: OR 2.07; 95% CI 1.03, 4.18), depression (PP: OR 2.13; 95% CI 1.16, 3.90 and EPP: OR 2.93; 95% CI 1.51, 5.66), pain (PP: OR 2.69; 95% CI 1.68, 4.30 and EPP: OR 2.74; 95% CI 1.56, 4.82), heart disease (PP: OR 2.51; 95% CI 1.54, 4.08 and EPP: OR 4.63; 95% CI 2.45, 8.74) and obstructive pulmonary disease (including asthma or chronic obstructive pulmonary disease) [PP: OR 2.79; 95% CI 1.24, 6.25 and EPP: OR 6.82; 95% CI 2.87, 16.20]. Conclusions: The study indicates that the factors associated with PP and EPP are not uniform. Age >= 85 years, female gender and moderate self-reported health were factors associated only with EPP, while poor self-reported health and several specific disease states were associated with both PP and EPP. The high number of drugs per diagnosis observed in this study calls for a thorough assessment of the need for and outcomes associated with use of these drugs.. health-care utilization| medication use| older-people| managed care| risk-factors| prescription| events| home| population| physicians.	2009	health-care utilization| medication use| older-people| managed care| risk-factors| prescription| events| home| population| physicians	Jyrkka, J; Enlund, H; Korhonen, MJ; Sulkava, R; Hartikainen, S	Patterns of Drug Use and Factors Associated with Polypharmacy and Excessive Polypharmacy in Elderly Persons Results of the Kuopio 75+Study: A Cross-Sectional Analysis		DRUGS & AGING		HEALTH-CARE UTILIZATION; MEDICATION USE; OLDER-PEOPLE; MANAGED CARE; RISK-FACTORS; PRESCRIPTION; EVENTS; HOME; POPULATION; PHYSICIANS	Background: Although the increasing use of drugs in elderly persons has raised many concerns in recent years, the process leading to polypharmacy (PP) and excessive polypharmacy (EPP) remains largely unknown. Objective: To describe the number and type of drugs used and to evaluate the role of different factors associated with PP (i.e. 6-9 drugs) and EPP (i.e. >= 10 drugs), with special reference to the number and type of medical diagnoses and symptoms, in a population of home-dwelling elderly persons aged >= 75 years. Methods: The study was a cross-sectional analysis of a population-based cohort in 1998. The population consisted of home-dwelling elderly persons aged >= 75 years in the city of Kuopio, Finland. The data for the analysis were obtained from the Kuopio 75+ Study, which drew a random sample of 700 elderly residents aged >= 75 years living in the city of Kuopio from the population register. Of these, 601 attended a structured clinical examination and an interview carried out by a geriatrician and a trained nurse in 1998. For this analysis, all home-dwelling elderly participants (n=523) were included. Study data were expressed as proportions and means with standard deviations. The factors associated with PP and EPP were examined by multinomial logistic regression. Results: The most commonly used drugs were cardiovascular drugs (97% in EPP, 94% in PP and 59% in non-PP group) and analgesics (89%, 76% and 54%), respectively. Use of psychotropics was markedly higher in the EPP group (77%) than in the PP (42%) and non-PP groups (20%). The mean number of drugs per diagnosis was 3.6 in the EPP group, 2.6 in the PP group and 1.6 in the non-PP group. Factors associated only with EPP were moderate self-reported health (odds ratio [OR] 2.05; 95% CI 1.08, 3.89), female gender (OR 2.43; 95% CI 1.27, 4.65) and age >= 85 years (OR 2.84; 95% CI 1.41, 5.72). Factors that were associated with both PP and EPP included poor self-reported health (PP: OR 2.15; 95% CI 1.01, 4.59 and EPP: OR 6.02; 95% CI 2.55, 14.20), diabetes mellitus (PP: OR 2.28; 95% CI 1.26, 4.15 and EPP: OR 2.07; 95% CI 1.03, 4.18), depression (PP: OR 2.13; 95% CI 1.16, 3.90 and EPP: OR 2.93; 95% CI 1.51, 5.66), pain (PP: OR 2.69; 95% CI 1.68, 4.30 and EPP: OR 2.74; 95% CI 1.56, 4.82), heart disease (PP: OR 2.51; 95% CI 1.54, 4.08 and EPP: OR 4.63; 95% CI 2.45, 8.74) and obstructive pulmonary disease (including asthma or chronic obstructive pulmonary disease) [PP: OR 2.79; 95% CI 1.24, 6.25 and EPP: OR 6.82; 95% CI 2.87, 16.20]. Conclusions: The study indicates that the factors associated with PP and EPP are not uniform. Age >= 85 years, female gender and moderate self-reported health were factors associated only with EPP, while poor self-reported health and several specific disease states were associated with both PP and EPP. The high number of drugs per diagnosis observed in this study calls for a thorough assessment of the need for and outcomes associated with use of these drugs.	46	75	2009	11		Geriatrics & Gerontology; Pharmacology & Pharmacy
Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. Oxidative stress is important in dendritic cell (DC) activation. Environmental particulate matter (PM) directs pro-oxidant activities that may alter DC function. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates expression of antioxidant and detoxification genes. Oxidative stress and defective antioxidant responses may contribute to the exacerbations of asthma. We hypothesized that PM would impart differential responses by Nrf2 wild-type DCs as compared with Nrf2(-/-) DCs. We found that the deletion of Nrf2 affected important constitutive functions of both bone marrow-derived and highly purified myeloid lung DCs such as the secretion of inflammatory cytokines and their ability to take up exogenous Ag. Stimulation of Nrf2(-/-) DCs with PM augmented oxidative stress and cytokine production as compared with resting or Nrf2(+/+) DCs. This was associated with the enhanced induction of Nrf2-regulated antioxidant genes. In contrast to Nrf2(+/+) DCs, coincubation of Nrf2(-/-) DCs with PM and the antioxidant N-acetyl cysteine attenuated PM-induced up-regulation of CD80 and CD86. Our studies indicate a previously underappreciated role of Nrf2 in innate immunity and suggest that deficiency in Nrf2-dependent pathways may be involved in susceptibility to the adverse health effects of air pollution in part by promoting Th2 cytokine responses in the absence of functional Nrf2. Moreover, our studies have uncovered a hierarchal response to oxidative stress in terms of costimulatory molecule expression and cytokine secretion in DCs and suggest an important role of heightened oxidative stress in proallergic Th2-mediated immune responses orchestrated by DCs.. heme oxygenase-1 expression| exhaust particle chemicals| airway inflammation| in-vivo| t-cells| allergic inflammation| costimulatory molecules| enhances susceptibility| glutathione depletion| cytokine production.	OCT 1-2008	heme oxygenase-1 expression| exhaust particle chemicals| airway inflammation| in-vivo| t-cells| allergic inflammation| costimulatory molecules| enhances susceptibility| glutathione depletion| cytokine production	Williams, MA; Rangasamy, T; Bauer, SM; Killedar, S; Karp, M; Kensler, TW; Yamamoto, M; Breysse, P; Biswal, S; Georas, SN	Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter		JOURNAL OF IMMUNOLOGY		HEME OXYGENASE-1 EXPRESSION; EXHAUST PARTICLE CHEMICALS; AIRWAY INFLAMMATION; IN-VIVO; T-CELLS; ALLERGIC INFLAMMATION; COSTIMULATORY MOLECULES; ENHANCES SUSCEPTIBILITY; GLUTATHIONE DEPLETION; CYTOKINE PRODUCTION	Oxidative stress is important in dendritic cell (DC) activation. Environmental particulate matter (PM) directs pro-oxidant activities that may alter DC function. Nuclear erythroid 2 p45-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates expression of antioxidant and detoxification genes. Oxidative stress and defective antioxidant responses may contribute to the exacerbations of asthma. We hypothesized that PM would impart differential responses by Nrf2 wild-type DCs as compared with Nrf2(-/-) DCs. We found that the deletion of Nrf2 affected important constitutive functions of both bone marrow-derived and highly purified myeloid lung DCs such as the secretion of inflammatory cytokines and their ability to take up exogenous Ag. Stimulation of Nrf2(-/-) DCs with PM augmented oxidative stress and cytokine production as compared with resting or Nrf2(+/+) DCs. This was associated with the enhanced induction of Nrf2-regulated antioxidant genes. In contrast to Nrf2(+/+) DCs, coincubation of Nrf2(-/-) DCs with PM and the antioxidant N-acetyl cysteine attenuated PM-induced up-regulation of CD80 and CD86. Our studies indicate a previously underappreciated role of Nrf2 in innate immunity and suggest that deficiency in Nrf2-dependent pathways may be involved in susceptibility to the adverse health effects of air pollution in part by promoting Th2 cytokine responses in the absence of functional Nrf2. Moreover, our studies have uncovered a hierarchal response to oxidative stress in terms of costimulatory molecule expression and cytokine secretion in DCs and suggest an important role of heightened oxidative stress in proallergic Th2-mediated immune responses orchestrated by DCs.	75	75	2008	15		Immunology
Exhaled breath malondialdehyde as a marker of effect of exposure to air pollution in children with asthma. Background: Assessment of the adverse effects of oxidative stress related to air pollution is limited by the lack of biological markers of dose to the lungs. Objective: We evaluated the use of exhaled breath condensate (EBC) malondialdehyde as a biomarker of exposure to traffic-related pollution in children with asthma as part of a panel study in Mexico City. Methods: Standard spirometry and collection of EBC and nasal lavage were performed. Environmental monitoring sites were located within 5 km of the children's homes and schools. Data were analyzed by using generalized estimating equations. Results: A total of 480 samples of malondialdehyde were obtained from 107 patients with asthma, with a median level of 18.7 (interquartile range [IQR], 12.4-28.7) nmol. Ambient particulates less than 2.5 mu g/m(3) and ozone levels on the day of sampling were significantly associated with higher malondialdehyde levels. A 14.2-mu g/m(3) (IQR) increase in 8-hour moving average particulates less than 2.5 mu g/m(3) in size was associated with a 1.12-nmol increase in malondialdehyde and 4 15.9-ppb (IQR) increase in 8-hour moving average ozone with a 1.16-nmol increase in malondialdehyde. Malondialdehyde levels were inversely associated with forced vital capacity and FEV(1) and positively associated with IL-8 levels in nasal lavage. Conclusion: Exhaled breath condensate malondialdehyde was related to both air pollution exposure and changes in lung function and inflammatory markers.. asthma| clinical immunology| environment| epidemiology| pediatrics|oxidative stress| mexico-city| dna-damage| ozone exposure| in-vivo| condensate| lung| antioxidant| glutathione| aldehydes.	APR-2008	asthma| clinical immunology| environment| epidemiology| pediatrics|oxidative stress| mexico-city| dna-damage| ozone exposure| in-vivo| condensate| lung| antioxidant| glutathione| aldehydes	Romieu, I; Barraza-Villarreal, A; Escamilla-Nunez, C; Almstrand, AC; Diaz-Sanchez, D; Sly, PD; Olin, AC	Exhaled breath malondialdehyde as a marker of effect of exposure to air pollution in children with asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; clinical immunology; environment; epidemiology; pediatrics	OXIDATIVE STRESS; MEXICO-CITY; DNA-DAMAGE; OZONE EXPOSURE; IN-VIVO; CONDENSATE; LUNG; ANTIOXIDANT; GLUTATHIONE; ALDEHYDES	Background: Assessment of the adverse effects of oxidative stress related to air pollution is limited by the lack of biological markers of dose to the lungs. Objective: We evaluated the use of exhaled breath condensate (EBC) malondialdehyde as a biomarker of exposure to traffic-related pollution in children with asthma as part of a panel study in Mexico City. Methods: Standard spirometry and collection of EBC and nasal lavage were performed. Environmental monitoring sites were located within 5 km of the children's homes and schools. Data were analyzed by using generalized estimating equations. Results: A total of 480 samples of malondialdehyde were obtained from 107 patients with asthma, with a median level of 18.7 (interquartile range [IQR], 12.4-28.7) nmol. Ambient particulates less than 2.5 mu g/m(3) and ozone levels on the day of sampling were significantly associated with higher malondialdehyde levels. A 14.2-mu g/m(3) (IQR) increase in 8-hour moving average particulates less than 2.5 mu g/m(3) in size was associated with a 1.12-nmol increase in malondialdehyde and 4 15.9-ppb (IQR) increase in 8-hour moving average ozone with a 1.16-nmol increase in malondialdehyde. Malondialdehyde levels were inversely associated with forced vital capacity and FEV(1) and positively associated with IL-8 levels in nasal lavage. Conclusion: Exhaled breath condensate malondialdehyde was related to both air pollution exposure and changes in lung function and inflammatory markers.	34	75	2008	7	10.1016/j.jaci.2007.12.004	Allergy; Immunology
Assessment of Bet v 1-specific CD4(+) T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers. In this study, we used HLA-DRB1*0101, DRB1*0401, and DRBI*1501 peptide tetramers combined with cytokine surface capture assays to characterize CD4(+) T cell responses against the immunodominant T cell epitope (peptide 141-155) from the major birch pollen allergen Bet v 1, in both healthy and allergic individuals. We could detect Bet v I-specific T cells in the PBMC of 20 birch pollen allergic patients, but also in 9 of 9 healthy individuals tested. Analysis at a single-cell level revealed that allergen-specific CD4(+) T cells from healthy individuals secrete IFN-gamma and IL-10 in response to the allergen, whereas cells from allergic patients are bona fide Th2 cells (producing mostly IL-5, some IL-10, but no IFN-gamma), as corroborated by patterns of cytokines produced by T cell clones. A fraction of Bet v 1-specific cells isolated from healthy, but not allergic, individuals also expresses CTLA-4, glucocorticoid-induced TNF receptor, and Foxp 3, indicating that they represent regulatory T cells. In this model of seasonal exposure to allergen, we also demonstrate the tremendous dynamics of T cell responses in both allergic and nonallergic individuals during the peak pollen season, with an expansion of Bet v 1-specific precursors from 10(-6) to 10(-3) among circulating CD4(+) T lymphocytes. Allergy vaccines should be designed to recapitulate such naturally protective Th1/regulatory T cell responses observed in healthy individuals.. birch pollen allergen| bet-v-i| sublingual immunotherapy| regulatory-cells| immune deviation| dendritic cells| grass-pollen| tgf-beta| mechanisms| induction.	APR 1-2008	birch pollen allergen| bet-v-i| sublingual immunotherapy| regulatory-cells| immune deviation| dendritic cells| grass-pollen| tgf-beta| mechanisms| induction	Van Overtvelt, L; Wambre, E; Maillere, B; von Hofe, E; Louise, A; Balazuc, AM; Bohle, B; Ebo, D; Leboulaire, C; Garcia, G; Moingeon, P	Assessment of Bet v 1-specific CD4(+) T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers		JOURNAL OF IMMUNOLOGY		BIRCH POLLEN ALLERGEN; BET-V-I; SUBLINGUAL IMMUNOTHERAPY; REGULATORY-CELLS; IMMUNE DEVIATION; DENDRITIC CELLS; GRASS-POLLEN; TGF-BETA; MECHANISMS; INDUCTION	In this study, we used HLA-DRB1*0101, DRB1*0401, and DRBI*1501 peptide tetramers combined with cytokine surface capture assays to characterize CD4(+) T cell responses against the immunodominant T cell epitope (peptide 141-155) from the major birch pollen allergen Bet v 1, in both healthy and allergic individuals. We could detect Bet v I-specific T cells in the PBMC of 20 birch pollen allergic patients, but also in 9 of 9 healthy individuals tested. Analysis at a single-cell level revealed that allergen-specific CD4(+) T cells from healthy individuals secrete IFN-gamma and IL-10 in response to the allergen, whereas cells from allergic patients are bona fide Th2 cells (producing mostly IL-5, some IL-10, but no IFN-gamma), as corroborated by patterns of cytokines produced by T cell clones. A fraction of Bet v 1-specific cells isolated from healthy, but not allergic, individuals also expresses CTLA-4, glucocorticoid-induced TNF receptor, and Foxp 3, indicating that they represent regulatory T cells. In this model of seasonal exposure to allergen, we also demonstrate the tremendous dynamics of T cell responses in both allergic and nonallergic individuals during the peak pollen season, with an expansion of Bet v 1-specific precursors from 10(-6) to 10(-3) among circulating CD4(+) T lymphocytes. Allergy vaccines should be designed to recapitulate such naturally protective Th1/regulatory T cell responses observed in healthy individuals.	57	75	2008	9		Immunology
Asthmatic symptoms among pupils in relation to winter indoor and outdoor air pollution in schools in Taiyuan, China. BACKGROUND: There are few studies on associations between children's respiratory heath and air pollution in schools in China. The industrial development and increased traffic may affect the indoor exposure to air pollutants in school environment. Moreover, there is a need to study respiratory effects of environmental tobacco smoke (ETS) and emissions from new building materials in homes in China. OBJECTIVES: We studied the associations between pupils' asthmatic symptoms and indoor and Outdoor air pollution in schools, as well as selected home exposures, in a coal-burning city in north China. METHODS: A questionnaire survey was administered to pupils (11-15 years of age) in 10 schools in urban Taiyuan, collecting data on respiratory health and selected home environmental factors. Indoor and outdoor school air pollutants and climate factors were measured in winter. RESULTS: A total of 1,993 pupils (90.2%) participated; 1.8% had cumulative asthma, 8.4% wheezing, 29.8% had daytime attacks of breathlessness, The indoor average concentrations of sulfur dioxide, nitrogen dioxide, ozone, and formaldehyde by class were 264.8, 39.4, 10.1, and 2.3 mu g/m(3), respectively. Outdoor levels were two to three times higher. Controlling for possible confounders, either wheeze or daytime or nocturnal attacks of breathlessness were positively associated with SO2, NO2, or formaldehyde. In addition, ETS and new furniture at home were risk factors for wheeze, daytime breathlessness, and respiratory infections. CONCLUSIONS: Indoor chemical air pollutants of mainly outdoor origin could be risk factors for pupils' respiratory symptoms at school, and home exposure to ETS and chemical emissions from new furniture could affect pupils' respiratory health.. air pollution| asthma| china| formaldehyde| indoor| nitrogen dioxide| ozone| outdoor| school| sulfur dioxide|sick building syndrome| volatile organic-compounds| respiratory symptoms| allergen levels| hong-kong| health| prevalence| smoking| environment| pollutants.	JAN-2008	air pollution| asthma| china| formaldehyde| indoor| nitrogen dioxide| ozone| outdoor| school| sulfur dioxide|sick building syndrome| volatile organic-compounds| respiratory symptoms| allergen levels| hong-kong| health| prevalence| smoking| environment| pollutants	Zhao, ZH; Zhang, Z; Wang, ZH; Ferm, M; Liang, YL; Norback, D	Asthmatic symptoms among pupils in relation to winter indoor and outdoor air pollution in schools in Taiyuan, China		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; asthma; China; formaldehyde; indoor; nitrogen dioxide; ozone; outdoor; school; sulfur dioxide	SICK BUILDING SYNDROME; VOLATILE ORGANIC-COMPOUNDS; RESPIRATORY SYMPTOMS; ALLERGEN LEVELS; HONG-KONG; HEALTH; PREVALENCE; SMOKING; ENVIRONMENT; POLLUTANTS	BACKGROUND: There are few studies on associations between children's respiratory heath and air pollution in schools in China. The industrial development and increased traffic may affect the indoor exposure to air pollutants in school environment. Moreover, there is a need to study respiratory effects of environmental tobacco smoke (ETS) and emissions from new building materials in homes in China. OBJECTIVES: We studied the associations between pupils' asthmatic symptoms and indoor and Outdoor air pollution in schools, as well as selected home exposures, in a coal-burning city in north China. METHODS: A questionnaire survey was administered to pupils (11-15 years of age) in 10 schools in urban Taiyuan, collecting data on respiratory health and selected home environmental factors. Indoor and outdoor school air pollutants and climate factors were measured in winter. RESULTS: A total of 1,993 pupils (90.2%) participated; 1.8% had cumulative asthma, 8.4% wheezing, 29.8% had daytime attacks of breathlessness, The indoor average concentrations of sulfur dioxide, nitrogen dioxide, ozone, and formaldehyde by class were 264.8, 39.4, 10.1, and 2.3 mu g/m(3), respectively. Outdoor levels were two to three times higher. Controlling for possible confounders, either wheeze or daytime or nocturnal attacks of breathlessness were positively associated with SO2, NO2, or formaldehyde. In addition, ETS and new furniture at home were risk factors for wheeze, daytime breathlessness, and respiratory infections. CONCLUSIONS: Indoor chemical air pollutants of mainly outdoor origin could be risk factors for pupils' respiratory symptoms at school, and home exposure to ETS and chemical emissions from new furniture could affect pupils' respiratory health.	48	75	2008	8	10.1289/ehp.10576	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Obesity and asthma: lessons from animal models. Epidemiological data indicate that obesity is a risk factor for asthma. These data are supported by observations in several murine models of obesity. Ob/ob, db/db, and Cpe(fat) mice each exhibit innate airway hyperresponsiveness, a characteristic feature of asthma. These mice also respond more vigorously to common asthma triggers, including ozone. Here we discuss the implications of these data with respect to several mechanisms proposed to explain the relationship between obesity and asthma: 1) common etiologies; 2) comorbidities; 3) mechanical factors; and 4) adipokines. We focus on the role of adipokines, especially TNF-alpha, IL-6, leptin, and adiponectin. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to novel therapeutic strategies for treatment of the obese asthmatic subject.. mice| leptin| adiponectin| tumor necrosis factor-alpha| interleukin-6| adipokines|body-mass index| necrosis-factor-alpha| interleukin-6 receptor gene| induced airway inflammation| induced lung inflammation| apparently healthy-men| emergency-room visits| acute-phase reactants| acute ozone exposure| diet-induced obesity.	FEB-2007	mice| leptin| adiponectin| tumor necrosis factor-alpha| interleukin-6| adipokines|body-mass index| necrosis-factor-alpha| interleukin-6 receptor gene| induced airway inflammation| induced lung inflammation| apparently healthy-men| emergency-room visits| acute-phase reactants| acute ozone exposure| diet-induced obesity	Shore, SA	Obesity and asthma: lessons from animal models		JOURNAL OF APPLIED PHYSIOLOGY	mice; leptin; adiponectin; tumor necrosis factor-alpha; interleukin-6; adipokines	BODY-MASS INDEX; NECROSIS-FACTOR-ALPHA; INTERLEUKIN-6 RECEPTOR GENE; INDUCED AIRWAY INFLAMMATION; INDUCED LUNG INFLAMMATION; APPARENTLY HEALTHY-MEN; EMERGENCY-ROOM VISITS; ACUTE-PHASE REACTANTS; ACUTE OZONE EXPOSURE; DIET-INDUCED OBESITY	Epidemiological data indicate that obesity is a risk factor for asthma. These data are supported by observations in several murine models of obesity. Ob/ob, db/db, and Cpe(fat) mice each exhibit innate airway hyperresponsiveness, a characteristic feature of asthma. These mice also respond more vigorously to common asthma triggers, including ozone. Here we discuss the implications of these data with respect to several mechanisms proposed to explain the relationship between obesity and asthma: 1) common etiologies; 2) comorbidities; 3) mechanical factors; and 4) adipokines. We focus on the role of adipokines, especially TNF-alpha, IL-6, leptin, and adiponectin. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to novel therapeutic strategies for treatment of the obese asthmatic subject.	157	75	2007	13	10.1152/japplphysiol.00847.2006	Physiology; Sport Sciences
Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults. Background: Respiratory syncytial virus (RSV) is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma. Methods: To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 x 10(5) TCID50/g body weight) and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined. Results: RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-alpha levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV. Conclusion: Neonatal RSV exposure results in long term pulmonary inflammation and exacerbates allergic airways disease. The early increase in TNF-alpha in the bronchoalveolar lavage implicates this inflammatory cytokine in orchestrating these events. Finally, the data presented emphasize IL-13 and TNF-alpha as potential therapeutic targets for treating RSV induced-asthma.. bronchiolitis| infection| infancy| disease| allergy| asthma| age| hyperresponsiveness| inflammation| enhancement.	AUG 7-2006	bronchiolitis| infection| infancy| disease| allergy| asthma| age| hyperresponsiveness| inflammation| enhancement	You, DH; Becnel, D; Wang, K; Ripple, M; Daly, M; Cormier, SA	Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults		RESPIRATORY RESEARCH		BRONCHIOLITIS; INFECTION; INFANCY; DISEASE; ALLERGY; ASTHMA; AGE; HYPERRESPONSIVENESS; INFLAMMATION; ENHANCEMENT	Background: Respiratory syncytial virus (RSV) is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma. Methods: To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 x 10(5) TCID50/g body weight) and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined. Results: RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-alpha levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV. Conclusion: Neonatal RSV exposure results in long term pulmonary inflammation and exacerbates allergic airways disease. The early increase in TNF-alpha in the bronchoalveolar lavage implicates this inflammatory cytokine in orchestrating these events. Finally, the data presented emphasize IL-13 and TNF-alpha as potential therapeutic targets for treating RSV induced-asthma.	29	75	2006	10	10.1186/1465-9921-7-107	Respiratory System
The atypical pneumonias: clinical diagnosis and importance. The most common atypical pneumonias are caused by three zoonotic pathogens, Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever), and three nonzoonotic pathogens, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella. These atypical agents, unlike the typical pathogens, often cause extrapulmonary manifestations. Atypical CAPs are systemic infectious diseases with a pulmonary component and may be differentiated clinically from typical CAPs by the pattern of extrapulmonary organ involvement which is characteristic for each atypical CAP. Zoonotic pneumonias may be eliminated from diagnostic consideration with a negative contact history. The commonest clinical problem is to differentiate legionnaire's disease from typical CAP as well as from C. pneumoniae or M. pneumonia infection. Legionella is the most important atypical pathogen in terms of severity. It may be clinically differentiated from typical CAP and other atypical pathogens by the use of a weighted point system of syndromic diagnosis based on the characteristic pattern of extrapulmonary features. Because legionnaire's disease often presents as severe CAP, a presumptive diagnosis of Legionella should prompt specific testing and empirical anti-Legionella therapy such as the Winthrop-University Hospital Infectious Disease Division's weighted point score system. Most atypical pathogens are difficult or dangerous to isolate and a definitive laboratory diagnosis is usually based on indirect, i.e., direct flourescent antibody (DFA), indirect flourescent antibody (IFA). Atypical CAP is virtually always monomicrobial; increased IFA IgG tests indicate past exposure and not concurrent infection. Anti-Legionella antibiotics include macrolides, doxycycline, rifampin, quinolones, and telithromycin. The drugs with the highest level of anti-Legionella activity are quinolones and telithromycin. Therapy is usually continued for 2 weeks if potent anti-Legionella drugs are used. In adults, M. pneumoniae and C. pneumoniae may exacerbate or cause asthma. The importance of the atypical pneumonias is not related to their frequency (similar to 15% of CAPs), but to difficulties in their diagnosis, and their nonresponsiveness to beta-lactam therapy. Because of the potential role of C. pneumoniae in coronary artery disease and multiple sclerosis (MS), and the role of M. pneumoniae and C. pneumoniae in causing or exacerbating asthma, atypical CAPs also have public health importance.. atypical pneumonias| clinical diagnosis of legionnaire's disease| community-acquired pneumonia| doxycycline| legionnaire's disease| mycoplasma pneumonia| chlamydia pneumonia| quinolones| review| telithromycin| therapy of legionella|community-acquired pneumonia| respiratory-tract infections| chlamydia-pneumoniae| mycoplasma-pneumoniae| multiple-sclerosis| early-switch| legionella-pneumonia| legionnaires-disease| ambulatory patients| therapy.	MAY-2006	atypical pneumonias| clinical diagnosis of legionnaire's disease| community-acquired pneumonia| doxycycline| legionnaire's disease| mycoplasma pneumonia| chlamydia pneumonia| quinolones| review| telithromycin| therapy of legionella|community-acquired pneumonia| respiratory-tract infections| chlamydia-pneumoniae| mycoplasma-pneumoniae| multiple-sclerosis| early-switch| legionella-pneumonia| legionnaires-disease| ambulatory patients| therapy	Cunha, BA	The atypical pneumonias: clinical diagnosis and importance		CLINICAL MICROBIOLOGY AND INFECTION	atypical pneumonias; clinical diagnosis of legionnaire's disease; community-acquired pneumonia; doxycycline; legionnaire's disease; Mycoplasma pneumonia; Chlamydia pneumonia; quinolones; review; telithromycin; therapy of Legionella	COMMUNITY-ACQUIRED PNEUMONIA; RESPIRATORY-TRACT INFECTIONS; CHLAMYDIA-PNEUMONIAE; MYCOPLASMA-PNEUMONIAE; MULTIPLE-SCLEROSIS; EARLY-SWITCH; LEGIONELLA-PNEUMONIA; LEGIONNAIRES-DISEASE; AMBULATORY PATIENTS; THERAPY	The most common atypical pneumonias are caused by three zoonotic pathogens, Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), and Coxiella burnetii (Q fever), and three nonzoonotic pathogens, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella. These atypical agents, unlike the typical pathogens, often cause extrapulmonary manifestations. Atypical CAPs are systemic infectious diseases with a pulmonary component and may be differentiated clinically from typical CAPs by the pattern of extrapulmonary organ involvement which is characteristic for each atypical CAP. Zoonotic pneumonias may be eliminated from diagnostic consideration with a negative contact history. The commonest clinical problem is to differentiate legionnaire's disease from typical CAP as well as from C. pneumoniae or M. pneumonia infection. Legionella is the most important atypical pathogen in terms of severity. It may be clinically differentiated from typical CAP and other atypical pathogens by the use of a weighted point system of syndromic diagnosis based on the characteristic pattern of extrapulmonary features. Because legionnaire's disease often presents as severe CAP, a presumptive diagnosis of Legionella should prompt specific testing and empirical anti-Legionella therapy such as the Winthrop-University Hospital Infectious Disease Division's weighted point score system. Most atypical pathogens are difficult or dangerous to isolate and a definitive laboratory diagnosis is usually based on indirect, i.e., direct flourescent antibody (DFA), indirect flourescent antibody (IFA). Atypical CAP is virtually always monomicrobial; increased IFA IgG tests indicate past exposure and not concurrent infection. Anti-Legionella antibiotics include macrolides, doxycycline, rifampin, quinolones, and telithromycin. The drugs with the highest level of anti-Legionella activity are quinolones and telithromycin. Therapy is usually continued for 2 weeks if potent anti-Legionella drugs are used. In adults, M. pneumoniae and C. pneumoniae may exacerbate or cause asthma. The importance of the atypical pneumonias is not related to their frequency (similar to 15% of CAPs), but to difficulties in their diagnosis, and their nonresponsiveness to beta-lactam therapy. Because of the potential role of C. pneumoniae in coronary artery disease and multiple sclerosis (MS), and the role of M. pneumoniae and C. pneumoniae in causing or exacerbating asthma, atypical CAPs also have public health importance.	100	75	2006	13	10.1111/j.1469-0691.2006.01393.x	Infectious Diseases; Microbiology
Asthma and farm exposures in a cohort of rural Iowa children. Epidemiologic studies of farm children are of international interest because farm children are less often atopic, have less allergic disease, and often have less asthma than do nonfarm children-findings consistent with the hygiene hypothesis. We studied a cohort of rural Iowa children to determine the association between farm.and other environmental risk factors with four asthma outcomes: doctor-diagnosed asthma, doctor-diagnosed asthma/medication for wheeze, current wheeze, and cough with exercise. Doctor-diagnosed asthma prevalence was 12%, but at least one of these four health outcomes was found in more than a third of the cohort. Multivariable models of the four health outcomes found independent associations between male sex (three asthma outcomes), age (three asthma outcomes), a personal history of allergies (four asthma outcomes), family history of allergic disease (two asthma outcomes), premature birth (one asthma outcome), early respiratory infection (three asthma outcomes), high-risk birth (two asthma outcomes), and farm exposure to raising swine and adding antibiotics to feed (two asthma outcomes). The high prevalence of rural childhood asthma and asthma symptoms underscores the need for asthma screening programs and improved asthma diagnosis and treatment. The high prevalence of asthma health outcomes among farm children living on farms that raise swine (44.1 %, p = 0.01) and raise swine and add antibiotics to feed (55.8%, p = 0.013), despite lower rates of atopy and personal histories of allergy, suggests the need for awareness and prevention measures and more population-based studies to further assess environmental and genetic determinants of asthma among farm children.. agricultural occupational exposures| ammonia| animal feeding operations| asthma| asthma diagnosis and treatment| asthma health care policy| asthma school screening| asthma underdiagnosis| asthma undertreatment| children| chronic wheeze| cough with exercise| farming| genetic selection| hydrogen sulfide| hygiene hypothesis| odor| rural|allergic sensitization| early-childhood| early-life| hay-fever| endotoxin| health| prevalence| diseases| atopy| risk.	MAR-2005	agricultural occupational exposures| ammonia| animal feeding operations| asthma| asthma diagnosis and treatment| asthma health care policy| asthma school screening| asthma underdiagnosis| asthma undertreatment| children| chronic wheeze| cough with exercise| farming| genetic selection| hydrogen sulfide| hygiene hypothesis| odor| rural|allergic sensitization| early-childhood| early-life| hay-fever| endotoxin| health| prevalence| diseases| atopy| risk	Merchant, JA; Naleway, AL; Svendsen, ER; Kelly, KM; Burmeister, LF; Stromquist, AM; Taylor, CD; Thorne, PS; Reynolds, SJ; Sanderson, WT; Chrischilles, EA	Asthma and farm exposures in a cohort of rural Iowa children		ENVIRONMENTAL HEALTH PERSPECTIVES	agricultural occupational exposures; ammonia; animal feeding operations; asthma; asthma diagnosis and treatment; asthma health care policy; asthma school screening; asthma underdiagnosis; asthma undertreatment; children; chronic wheeze; cough with exercise; farming; genetic selection; hydrogen sulfide; hygiene hypothesis; odor; rural	ALLERGIC SENSITIZATION; EARLY-CHILDHOOD; EARLY-LIFE; HAY-FEVER; ENDOTOXIN; HEALTH; PREVALENCE; DISEASES; ATOPY; RISK	Epidemiologic studies of farm children are of international interest because farm children are less often atopic, have less allergic disease, and often have less asthma than do nonfarm children-findings consistent with the hygiene hypothesis. We studied a cohort of rural Iowa children to determine the association between farm.and other environmental risk factors with four asthma outcomes: doctor-diagnosed asthma, doctor-diagnosed asthma/medication for wheeze, current wheeze, and cough with exercise. Doctor-diagnosed asthma prevalence was 12%, but at least one of these four health outcomes was found in more than a third of the cohort. Multivariable models of the four health outcomes found independent associations between male sex (three asthma outcomes), age (three asthma outcomes), a personal history of allergies (four asthma outcomes), family history of allergic disease (two asthma outcomes), premature birth (one asthma outcome), early respiratory infection (three asthma outcomes), high-risk birth (two asthma outcomes), and farm exposure to raising swine and adding antibiotics to feed (two asthma outcomes). The high prevalence of rural childhood asthma and asthma symptoms underscores the need for asthma screening programs and improved asthma diagnosis and treatment. The high prevalence of asthma health outcomes among farm children living on farms that raise swine (44.1 %, p = 0.01) and raise swine and add antibiotics to feed (55.8%, p = 0.013), despite lower rates of atopy and personal histories of allergy, suggests the need for awareness and prevention measures and more population-based studies to further assess environmental and genetic determinants of asthma among farm children.	43	75	2005	7	10.1289/ehp.7240	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Detrimental effects of beta-blockers in COPD - A concern for nonselective beta-blockers. Introduction: beta-Blockers are known to worsen FEV1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment. Design: A double-blind, placebo-controlled, randomized, cross-over study. Setting: An ambulatory, hospital outpatient clinic of pulmonary diseases. Patients: Patients with mild-to-moderate irreversible COPD and AHR. Intervention: Fifteen patients received propranolol (80 mg), metoprolol (100 mg), celiprolol (200 mg), or placebo for 4 days, followed by a washout period >= 3 days. On day 4 of treatment, FEV1 and PC20 were assessed. Immediately hereafter, formoterol (12 mu g) was administered and FEV1 was measured for up to 30 min. Results: PC20 was significantly lower (p < 0.01) with propranolol and metoprolol treatment (geometric means, 2.06 mg/mL and 2.02 mg/mL, respectively) than with placebo (3.16 mg/mL) or celiprolol (3.41 mg/mL). FEV1 deteriorated only after propranolol treatment (2.08 +/- 0.31 L) [mean +/- SD] compared with placebo (2.24 +/- 0.37 L). The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV1 at 3 min, 6.7 +/- 8.9%) but was unaffected by the other beta-blockers (16.9 +/- 9.8%, 22 +/- 11.6%, and 16.9 +/- 9.0% for placebo, metoprolol, and celiprolol, respectively). Conclusions: Pulmonary effects did not occur by celiprolol. Only propranolol reduced FEV1 and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of beta-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a P-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV1 AHR, and response to additional beta(2)-agonists.. airway hyperresponsiveness| beta-blockers| copd|obstructive pulmonary-disease| air-flow obstruction| working party standardization| european respiratory society| lung-function| severe bronchoconstriction| official statement| chronic-bronchitis| methacholine| responsiveness.	MAR-2005	airway hyperresponsiveness| beta-blockers| copd|obstructive pulmonary-disease| air-flow obstruction| working party standardization| european respiratory society| lung-function| severe bronchoconstriction| official statement| chronic-bronchitis| methacholine| responsiveness	van der Woude, HJ; Zaagsma, J; Postma, DS; Winter, TH; van Hulst, M; Aalbers, R	Detrimental effects of beta-blockers in COPD - A concern for nonselective beta-blockers		CHEST	airway hyperresponsiveness; beta-blockers; COPD	OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; WORKING PARTY STANDARDIZATION; EUROPEAN RESPIRATORY SOCIETY; LUNG-FUNCTION; SEVERE BRONCHOCONSTRICTION; OFFICIAL STATEMENT; CHRONIC-BRONCHITIS; METHACHOLINE; RESPONSIVENESS	Introduction: beta-Blockers are known to worsen FEV1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment. Design: A double-blind, placebo-controlled, randomized, cross-over study. Setting: An ambulatory, hospital outpatient clinic of pulmonary diseases. Patients: Patients with mild-to-moderate irreversible COPD and AHR. Intervention: Fifteen patients received propranolol (80 mg), metoprolol (100 mg), celiprolol (200 mg), or placebo for 4 days, followed by a washout period >= 3 days. On day 4 of treatment, FEV1 and PC20 were assessed. Immediately hereafter, formoterol (12 mu g) was administered and FEV1 was measured for up to 30 min. Results: PC20 was significantly lower (p < 0.01) with propranolol and metoprolol treatment (geometric means, 2.06 mg/mL and 2.02 mg/mL, respectively) than with placebo (3.16 mg/mL) or celiprolol (3.41 mg/mL). FEV1 deteriorated only after propranolol treatment (2.08 +/- 0.31 L) [mean +/- SD] compared with placebo (2.24 +/- 0.37 L). The fast bronchodilating effect of formoterol was hampered by propranolol (mean increase in FEV1 at 3 min, 6.7 +/- 8.9%) but was unaffected by the other beta-blockers (16.9 +/- 9.8%, 22 +/- 11.6%, and 16.9 +/- 9.0% for placebo, metoprolol, and celiprolol, respectively). Conclusions: Pulmonary effects did not occur by celiprolol. Only propranolol reduced FEV1 and the bronchodilating effect of formoterol. Both metoprolol and propranolol increased AHR. Thus, different classes of beta-blockers have different pulmonary effects. The anticipated beneficial cardiovascular effects of a P-blocker must be weighted against the putative detrimental pulmonary effects, ie, effect on FEV1 AHR, and response to additional beta(2)-agonists.	31	75	2005	7	10.1378/chest.127.3.818	General & Internal Medicine; Respiratory System
Cat and dust mite sensitivity and tolerance in relation to wheezing among children raised with high exposure to both allergens. Background: Recent evidence has suggested that high exposure to cat allergens is associated with decreased prevalence of sensitization to cat and, in some studies, decreased asthma. Objective: Our objective was to study antibodies to cat and mite allergens and their relationship to wheezing in a country with high exposure to both allergens. Methods: Sera from 112 wheezing and 112 control children aged 10 to 11 years in a nested case-control study in New Zealand were assayed for specific IgE antibody, as well as IgG antibody and IgG4 antibody, to Der p 1 and Fel d 1. Results: IgE antibody to both mite (99/224) and cat (41/224) were strongly associated with wheezing (odds ratios, 5.2 and 6.5, respectively). Children who had ever lived with a cat were less likely to have IgE antibody to cat (20/141 vs 21/83, P <.04); however, cat ownership had no effect on IgE antibody to mite (67/141 vs 32/83, P =.23). Among sensitized children, cat ownership was associated with a lower prevalence of IgE antibody to cat (28% vs 66%, P <.001), and this analysis remained significant after exclusion of children whose families had chosen not to own a cat. Among sensitized subjects, the mean titer of IgE antibody to cat (1.7 IU/mL) was 10-fold lower than for mite (22.1 IU/mL). A cat in the home had no significant effect on endotoxin or mite allergen in house dust, whereas cat allergen was much higher (40.8 vs 3.3 mug/g). Conclusion: The response to these 2 allergens was distinct on the basis of the prevalence of sensitization, the titer of IgE antibody, and the effect of cat ownership. The results suggest that induction of tolerance to cat allergen is an allergen-specific phenomenon that cannot be attributed to endotoxin or family choice. The strength of the IgE antibody response to dust mite in humid climates could contribute to the increased prevalence and severity of asthma.. asthma| cat| mite| tolerance| high exposure|modified th2 response| childhood asthma| atopic-dermatitis| immune-response| new-zealand| sensitization| antibodies| determinants| prevalence| endotoxin.	JAN-2005	asthma| cat| mite| tolerance| high exposure|modified th2 response| childhood asthma| atopic-dermatitis| immune-response| new-zealand| sensitization| antibodies| determinants| prevalence| endotoxin	Erwin, EA; Wickens, K; Custis, NJ; Siebers, R; Woodfolk, J; Barry, D; Crane, J; Platts-Mills, TAE	Cat and dust mite sensitivity and tolerance in relation to wheezing among children raised with high exposure to both allergens		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; cat; mite; tolerance; high exposure	MODIFIED TH2 RESPONSE; CHILDHOOD ASTHMA; ATOPIC-DERMATITIS; IMMUNE-RESPONSE; NEW-ZEALAND; SENSITIZATION; ANTIBODIES; DETERMINANTS; PREVALENCE; ENDOTOXIN	Background: Recent evidence has suggested that high exposure to cat allergens is associated with decreased prevalence of sensitization to cat and, in some studies, decreased asthma. Objective: Our objective was to study antibodies to cat and mite allergens and their relationship to wheezing in a country with high exposure to both allergens. Methods: Sera from 112 wheezing and 112 control children aged 10 to 11 years in a nested case-control study in New Zealand were assayed for specific IgE antibody, as well as IgG antibody and IgG4 antibody, to Der p 1 and Fel d 1. Results: IgE antibody to both mite (99/224) and cat (41/224) were strongly associated with wheezing (odds ratios, 5.2 and 6.5, respectively). Children who had ever lived with a cat were less likely to have IgE antibody to cat (20/141 vs 21/83, P <.04); however, cat ownership had no effect on IgE antibody to mite (67/141 vs 32/83, P =.23). Among sensitized children, cat ownership was associated with a lower prevalence of IgE antibody to cat (28% vs 66%, P <.001), and this analysis remained significant after exclusion of children whose families had chosen not to own a cat. Among sensitized subjects, the mean titer of IgE antibody to cat (1.7 IU/mL) was 10-fold lower than for mite (22.1 IU/mL). A cat in the home had no significant effect on endotoxin or mite allergen in house dust, whereas cat allergen was much higher (40.8 vs 3.3 mug/g). Conclusion: The response to these 2 allergens was distinct on the basis of the prevalence of sensitization, the titer of IgE antibody, and the effect of cat ownership. The results suggest that induction of tolerance to cat allergen is an allergen-specific phenomenon that cannot be attributed to endotoxin or family choice. The strength of the IgE antibody response to dust mite in humid climates could contribute to the increased prevalence and severity of asthma.	32	75	2005	6	10.1016/j.jaci.2004.10.030	Allergy; Immunology
Frequent use of chemical household products is associated with persistent wheezing in pre-school age children. Background: In the UK and other developed countries the prevalence of asthma symptoms has increased in recent years. This is likely to be the result of increased exposure to environmental factors. A study was undertaken to investigate the association between maternal use of chemical based products in the prenatal period and patterns of wheeze in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC), the frequency of use of 11 chemical based domestic products was determined from questionnaires completed by women during pregnancy and a total chemical burden (TCB) score was derived. Four mutually exclusive wheezing patterns were defined for the period from birth to 42 months based on parental questionnaire responses ( never wheezed, transient early wheeze, persistent wheeze, and late onset wheeze). Multinomial logistic regression models were used to assess the relationship between these wheezing outcomes and TCB exposure while accounting for numerous potential confounding variables. Complete data for analysis was available for 7019 of 13 971 (50%) children. Results: The mean (SD) TCB score was 9.4 (4.1), range 0 - 30. Increased use of domestic chemical based products was associated with persistent wheezing during early childhood ( adjusted odds ratio ( OR) per unit increase of TCB 1.06 (95% confidence interval (CI) 1.03 to 1.09)) but not with transient early wheeze or late onset wheeze. Children whose mothers had high TCB scores (>90th centile) were more than twice as likely to wheeze persistently throughout early childhood than children whose mothers had a low TCB score (<10th centile) ( adjusted OR 2.3 (95% CI 1.2 to 4.4)). Conclusion: These findings suggest that frequent use of chemical based products in the prenatal period is associated with persistent wheezing in young children. Follow up of this cohort is underway to determine whether TCB is associated with wheezing, asthma, and atopy at later stages in childhood.. volatile organic-compounds| respiratory symptoms| changing prevalence| school environment| maternal smoking| asthma| risk| schoolchildren| cleaners| indoor.	JAN-2005	volatile organic-compounds| respiratory symptoms| changing prevalence| school environment| maternal smoking| asthma| risk| schoolchildren| cleaners| indoor	Sherriff, A; Farrow, A; Golding, J; Henderson, J	Frequent use of chemical household products is associated with persistent wheezing in pre-school age children		THORAX		VOLATILE ORGANIC-COMPOUNDS; RESPIRATORY SYMPTOMS; CHANGING PREVALENCE; SCHOOL ENVIRONMENT; MATERNAL SMOKING; ASTHMA; RISK; SCHOOLCHILDREN; CLEANERS; INDOOR	Background: In the UK and other developed countries the prevalence of asthma symptoms has increased in recent years. This is likely to be the result of increased exposure to environmental factors. A study was undertaken to investigate the association between maternal use of chemical based products in the prenatal period and patterns of wheeze in early childhood. Methods: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC), the frequency of use of 11 chemical based domestic products was determined from questionnaires completed by women during pregnancy and a total chemical burden (TCB) score was derived. Four mutually exclusive wheezing patterns were defined for the period from birth to 42 months based on parental questionnaire responses ( never wheezed, transient early wheeze, persistent wheeze, and late onset wheeze). Multinomial logistic regression models were used to assess the relationship between these wheezing outcomes and TCB exposure while accounting for numerous potential confounding variables. Complete data for analysis was available for 7019 of 13 971 (50%) children. Results: The mean (SD) TCB score was 9.4 (4.1), range 0 - 30. Increased use of domestic chemical based products was associated with persistent wheezing during early childhood ( adjusted odds ratio ( OR) per unit increase of TCB 1.06 (95% confidence interval (CI) 1.03 to 1.09)) but not with transient early wheeze or late onset wheeze. Children whose mothers had high TCB scores (>90th centile) were more than twice as likely to wheeze persistently throughout early childhood than children whose mothers had a low TCB score (<10th centile) ( adjusted OR 2.3 (95% CI 1.2 to 4.4)). Conclusion: These findings suggest that frequent use of chemical based products in the prenatal period is associated with persistent wheezing in young children. Follow up of this cohort is underway to determine whether TCB is associated with wheezing, asthma, and atopy at later stages in childhood.	33	75	2005	5	10.1136/thx.2004.021154	Respiratory System
Activity profile of dust mite allergen extract using substrate libraries and functional proteomic microarrays. Enzymatic activity in the fecal droppings from the house dust mite has been postulated to contribute to the elicited allergic response. Screening dust mite extracts through 137,180 tetrapeptide fluorogenic substrates allowed for the characterization of proteolytic substrate specificity from the potential cysteine and serine proteases in the extract. The extract was further screened against a 4000 member peptide nucleic acid (PNA) encoded inhibitor library designed to target cysteine proteases using microarray detection. Affinity chromatography coupled with mass spectrometry identified Der p 1 as one of the proteases targeted by the PNA inhibitors in the dust mite lysate. A phenotypic readout of Der p 1 function in allergy progression was demonstrated by the inhibition of CD25 cleavage from T cells by dust mite extract that had been treated with the Der p I inhibitor identified from the PNA-encoded inhibitor library.. cysteine protease activity| dermatophagoides-pteronyssinus| enhances allergenicity| proteolytic activity| serine hydrolases| mass-spectrometry| der-p-1| specificity| inhibitor| proteinases.	OCT-2004	cysteine protease activity| dermatophagoides-pteronyssinus| enhances allergenicity| proteolytic activity| serine hydrolases| mass-spectrometry| der-p-1| specificity| inhibitor| proteinases	Harris, J; Mason, DE; Li, J; Burdick, KW; Backes, BJ; Chen, T; Shipway, A; Van Heeke, G; Gough, L; Ghaemmaghami, A; Shakib, F; Debaene, F; Winssinger, N	Activity profile of dust mite allergen extract using substrate libraries and functional proteomic microarrays		CHEMISTRY & BIOLOGY		CYSTEINE PROTEASE ACTIVITY; DERMATOPHAGOIDES-PTERONYSSINUS; ENHANCES ALLERGENICITY; PROTEOLYTIC ACTIVITY; SERINE HYDROLASES; MASS-SPECTROMETRY; DER-P-1; SPECIFICITY; INHIBITOR; PROTEINASES	Enzymatic activity in the fecal droppings from the house dust mite has been postulated to contribute to the elicited allergic response. Screening dust mite extracts through 137,180 tetrapeptide fluorogenic substrates allowed for the characterization of proteolytic substrate specificity from the potential cysteine and serine proteases in the extract. The extract was further screened against a 4000 member peptide nucleic acid (PNA) encoded inhibitor library designed to target cysteine proteases using microarray detection. Affinity chromatography coupled with mass spectrometry identified Der p 1 as one of the proteases targeted by the PNA inhibitors in the dust mite lysate. A phenotypic readout of Der p 1 function in allergy progression was demonstrated by the inhibition of CD25 cleavage from T cells by dust mite extract that had been treated with the Der p I inhibitor identified from the PNA-encoded inhibitor library.	44	75	2004	12	10.1016/j.chembiol.2004.08.008	Biochemistry & Molecular Biology
Carbon nanotubes, nanocrystal forms, and complex nanoparticle aggregates in common fuel-gas combustion sources and the ambient air. Aggregated multiwall carbon nanotubes (with diameters ranging from similar to3 to 30 nm) and related carbon nanocrystal forms ranging in size from 0.4 to 2 mum (average diameter) have been collected in the combustion streams for methane/ air, natural gas/air, and propane gas/air flames using a thermal precipitator. Individual particle aggregates were collected on carbon/formvar-coated 3 mm nickel grids and examined in a transmission electron microscope, utilizing bright-field imaging, selected-area electron diffraction analysis, and energy-dispersive X-ray spectrometry techniques. The natural gas and propane gas sources were domestic (kitchen) stoves, and similar particle aggregates collected in the outdoor air were correspondingly identified as carbon nanocrystal aggregates and sometimes more complex aggregates of silica nanocrystals intermixed with the carbon nanotubes and other carbon nanocrystals. Finally, and in light of the potential for methane-series gas burning as major sources of carbon nanocrystal aggregates in both the indoor and outdoor air, data for natural gas consumption and corresponding asthma deaths and incidence are examined with a degree of speculation regarding any significance in the correlations.. carbon nanotubes| aggregates| methane| propane| natural gas| transmission electron microscopy| health risks| home environment|ultrafine particles| mortality| climate| aerosol| health| size.	JUN-2004	carbon nanotubes| aggregates| methane| propane| natural gas| transmission electron microscopy| health risks| home environment|ultrafine particles| mortality| climate| aerosol| health| size	Murr, LE; Bang, JJ; Esquivel, EV; Guerrero, PA; Lopez, A	Carbon nanotubes, nanocrystal forms, and complex nanoparticle aggregates in common fuel-gas combustion sources and the ambient air		JOURNAL OF NANOPARTICLE RESEARCH	carbon nanotubes; aggregates; methane; propane; natural gas; transmission electron microscopy; health risks; home environment	ULTRAFINE PARTICLES; MORTALITY; CLIMATE; AEROSOL; HEALTH; SIZE	Aggregated multiwall carbon nanotubes (with diameters ranging from similar to3 to 30 nm) and related carbon nanocrystal forms ranging in size from 0.4 to 2 mum (average diameter) have been collected in the combustion streams for methane/ air, natural gas/air, and propane gas/air flames using a thermal precipitator. Individual particle aggregates were collected on carbon/formvar-coated 3 mm nickel grids and examined in a transmission electron microscope, utilizing bright-field imaging, selected-area electron diffraction analysis, and energy-dispersive X-ray spectrometry techniques. The natural gas and propane gas sources were domestic (kitchen) stoves, and similar particle aggregates collected in the outdoor air were correspondingly identified as carbon nanocrystal aggregates and sometimes more complex aggregates of silica nanocrystals intermixed with the carbon nanotubes and other carbon nanocrystals. Finally, and in light of the potential for methane-series gas burning as major sources of carbon nanocrystal aggregates in both the indoor and outdoor air, data for natural gas consumption and corresponding asthma deaths and incidence are examined with a degree of speculation regarding any significance in the correlations.	25	75	2004	11	10.1023/B:NANO.0000034651.91325.40	Chemistry; Science & Technology - Other Topics; Materials Science
Gene expression changes in peripheral blood-derived dendritic cells following exposure to a contact allergen. A critical step in the induction of allergic contact allergy is the activation and subsequent migration of Langerhans cells (LC), an important antigen presenting dendritic cell (DC) of the skin. As the Langerhans cells migrate, they undergo a maturation process. It has been proposed that contact allergen exposure can induce DC maturation. While changes in DC gene expression profiles induced by various maturation stimuli have been explored, there are no published reports describing genomic-scale analysis of the changes induced by chemical allergen exposure. Therefore, to explore the concept of chemical allergen-induced DC maturation and to identify genes that are regulated by exposure to allergens we examined, at the transcriptional level, the effects of exposure to a contact allergen on DC. Peripheral blood-derived DC were exposed for 24 h to either 1 mM or 5 mM dinitrobenzenesulfonic acid (DNBS). Changes in gene expression were analyzed using Affymetrix U95Av2 GeneChip(R). Comparison of mean signal values from replicate cultures revealed 173 genes that were significantly different (P less than or equal to 0.001) between 1 mM DNBS treated and untreated control DC and 1249 significant gene changes between 5 mM DNBS treated and control DC. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the observed transcript changes for selected genes in DC derived from a second donor. Comparison of the fold-changes in transcript levels between the two platforms and donors revealed a good correlation in both direction and magnitude. RT-PCR analysis was also used to assess the allergen specificity of a selected number of genes in DC derived from a third donor. Many of the gene expression changes were found to be induced only by exposure to the allergen, DNBS, and not by exposure to a structurally similar non-allergen, benzenesulfonic acid. A number of gene expression changes induced by allergen exposure were found to be consistent with what is known of the DC maturation process, and thus provide support for the theory of contact allergen-induced DC maturation. Additionally, it is hoped that some of the transcript changes identified through this approach will be shown to be suitable for use in the development of an in vitro predictive assay for contact sensitization. (C) 2004 Elsevier Ireland Ltd. All rights reserved.. contact allergy| dendritic cells| gene expression| in vitro method| dinitrobenzenesulfonic acid|epidermal langerhans cells| lymphocytic activation molecule| e-cadherin expression| class-ii molecules| costimulatory molecules| hla-dr| maturation| cytokines| haptens| sensitizers.	MAY 2-2004	contact allergy| dendritic cells| gene expression| in vitro method| dinitrobenzenesulfonic acid|epidermal langerhans cells| lymphocytic activation molecule| e-cadherin expression| class-ii molecules| costimulatory molecules| hla-dr| maturation| cytokines| haptens| sensitizers	Ryan, CA; Gildea, LA; Hulette, BC; Dearman, RJ; Kimber, I; Gerberick, GF	Gene expression changes in peripheral blood-derived dendritic cells following exposure to a contact allergen		TOXICOLOGY LETTERS	contact allergy; dendritic cells; gene expression; in vitro method; dinitrobenzenesulfonic acid	EPIDERMAL LANGERHANS CELLS; LYMPHOCYTIC ACTIVATION MOLECULE; E-CADHERIN EXPRESSION; CLASS-II MOLECULES; COSTIMULATORY MOLECULES; HLA-DR; MATURATION; CYTOKINES; HAPTENS; SENSITIZERS	A critical step in the induction of allergic contact allergy is the activation and subsequent migration of Langerhans cells (LC), an important antigen presenting dendritic cell (DC) of the skin. As the Langerhans cells migrate, they undergo a maturation process. It has been proposed that contact allergen exposure can induce DC maturation. While changes in DC gene expression profiles induced by various maturation stimuli have been explored, there are no published reports describing genomic-scale analysis of the changes induced by chemical allergen exposure. Therefore, to explore the concept of chemical allergen-induced DC maturation and to identify genes that are regulated by exposure to allergens we examined, at the transcriptional level, the effects of exposure to a contact allergen on DC. Peripheral blood-derived DC were exposed for 24 h to either 1 mM or 5 mM dinitrobenzenesulfonic acid (DNBS). Changes in gene expression were analyzed using Affymetrix U95Av2 GeneChip(R). Comparison of mean signal values from replicate cultures revealed 173 genes that were significantly different (P less than or equal to 0.001) between 1 mM DNBS treated and untreated control DC and 1249 significant gene changes between 5 mM DNBS treated and control DC. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the observed transcript changes for selected genes in DC derived from a second donor. Comparison of the fold-changes in transcript levels between the two platforms and donors revealed a good correlation in both direction and magnitude. RT-PCR analysis was also used to assess the allergen specificity of a selected number of genes in DC derived from a third donor. Many of the gene expression changes were found to be induced only by exposure to the allergen, DNBS, and not by exposure to a structurally similar non-allergen, benzenesulfonic acid. A number of gene expression changes induced by allergen exposure were found to be consistent with what is known of the DC maturation process, and thus provide support for the theory of contact allergen-induced DC maturation. Additionally, it is hoped that some of the transcript changes identified through this approach will be shown to be suitable for use in the development of an in vitro predictive assay for contact sensitization. (C) 2004 Elsevier Ireland Ltd. All rights reserved.	43	75	2004	16	10.1016/j.toxlet.2004.02.002	Toxicology
Determinants of endotoxin levels in living environments of farmers' children and their peers from rural areas. Background Lower frequencies of asthma and hayfever have been observed in children with contact to livestock. At school age, the amount of endotoxin measured in the dust of children's mattresses is inversely related to the occurrence of atopic asthma, hayfever and atopic sensitization both in children from farming and non-farming households. Objective The aim of the present study was to investigate which home and lifestyle characteristics of farm and non-farm families contribute to endotoxin levels measured in different indoor home environments. Methods In the framework of the Allergy and Endotoxin (ALEX) Study, endotoxin was measured in dust samples from the living room floor and the child's mattress of 319 farmers' families and 493 non-farming families, and in settled dust from stables. Endotoxin content of all dust samples was determined by a kinetic Limulus assay (Limulus-Amebocyte-Lysate test). Information about the child's activities on farms, home characteristics and cleaning behaviours was obtained from parental questionnaires. Results Endotoxin levels in stables did not predict the amount of endotoxin measured in floors or mattresses. However, a dose-dependent association between the child's activity on the farm and indoor home endotoxin levels was observed, both in farm and non-farm children. In non-farm children pet keeping and the frequency of floor cleaning were additionally associated with endotoxin levels, whereas in farm children parental farm activities, study area, time since last cleaning, the mattress type as well as younger age of the children contributed to increased microbial exposure. Conclusion These results demonstrate that regular contact to farm animals increases indoor home endotoxin concentrations, both in farm and non-farm children, and might thus explain the protective effect of contact to livestock on atopic outcomes. To assess children's individual exposure to a microbial environment, measures of mattress dust exposure are needed as stable endotoxin concentrations were not associated with indoor home levels.. allergy| children| exposure assessment| farm animals and pets| farming| house and stable dust| indoor endotoxin| living room floor| mattress|in-house dust| hay-fever| allergic sensitization| exposure| asthma| atopy| contaminants| protect| life| home.	MAR-2004	allergy| children| exposure assessment| farm animals and pets| farming| house and stable dust| indoor endotoxin| living room floor| mattress|in-house dust| hay-fever| allergic sensitization| exposure| asthma| atopy| contaminants| protect| life| home	Waser, M; Schierl, R; Von mutius, E; Maisch, S; Carr, D; Riedler, J; Eder, W; Schreuer, M; Nowak, D; Braun-Fahrlander, C	Determinants of endotoxin levels in living environments of farmers' children and their peers from rural areas		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; children; exposure assessment; farm animals and pets; farming; house and stable dust; indoor endotoxin; living room floor; mattress	IN-HOUSE DUST; HAY-FEVER; ALLERGIC SENSITIZATION; EXPOSURE; ASTHMA; ATOPY; CONTAMINANTS; PROTECT; LIFE; HOME	Background Lower frequencies of asthma and hayfever have been observed in children with contact to livestock. At school age, the amount of endotoxin measured in the dust of children's mattresses is inversely related to the occurrence of atopic asthma, hayfever and atopic sensitization both in children from farming and non-farming households. Objective The aim of the present study was to investigate which home and lifestyle characteristics of farm and non-farm families contribute to endotoxin levels measured in different indoor home environments. Methods In the framework of the Allergy and Endotoxin (ALEX) Study, endotoxin was measured in dust samples from the living room floor and the child's mattress of 319 farmers' families and 493 non-farming families, and in settled dust from stables. Endotoxin content of all dust samples was determined by a kinetic Limulus assay (Limulus-Amebocyte-Lysate test). Information about the child's activities on farms, home characteristics and cleaning behaviours was obtained from parental questionnaires. Results Endotoxin levels in stables did not predict the amount of endotoxin measured in floors or mattresses. However, a dose-dependent association between the child's activity on the farm and indoor home endotoxin levels was observed, both in farm and non-farm children. In non-farm children pet keeping and the frequency of floor cleaning were additionally associated with endotoxin levels, whereas in farm children parental farm activities, study area, time since last cleaning, the mattress type as well as younger age of the children contributed to increased microbial exposure. Conclusion These results demonstrate that regular contact to farm animals increases indoor home endotoxin concentrations, both in farm and non-farm children, and might thus explain the protective effect of contact to livestock on atopic outcomes. To assess children's individual exposure to a microbial environment, measures of mattress dust exposure are needed as stable endotoxin concentrations were not associated with indoor home levels.	25	75	2004	9	10.1111/j.1365-2222.2004.01873.x	Allergy; Immunology
Proximity of California public schools to busy roads. Residential proximity to busy roads has been associated with adverse health Outcomes, and school location may also be an important determinant of children's exposure to traffic-related pollutants. The goal of this study was to examine the characteristics of public schools (grades K-12) in California (n = 7,460) by proximity to major roads. We determined maximum daily traffic counts for all roads within 150 m of the school using a statewide road network and a geographic information system. Statewide, 173 schools (2.3%) with a total enrollment of 150,323 students were located within 150 m of high-traffic roads (greater than or equal to 50,000 vehides/day); 536 schools (7.2%) were within 150 m of medium-traffic roads (25,000-49,999 vehicles/day). Traffic exposure was related to race/ethnicity. For example, the overall percentage of nonwhite students was 78% at the schools located near high-traffic roads versus 60% at the schools with very low exposure (no streets with counted traffic data within 150 m). As the traffic exposure of schools increased, the percentage of both non-Hispanic black and Hispanic students attending the schools increased substantially. Traffic exposure was also related to school-based and census-tract-based socioeconomic indicators, including English language learners. The median percentage of children enrolled in free or reduced-price meal programs increased from 40.7% in the group with very low exposure to 60.5% in the highest exposure group. In summary, a substantial number of children in California attend schools dose to major roads with very high traffic counts, and a disproportionate number of those students are economically disadvantaged and nonwhite.. air pollution| children's health| environmental justice| ethnicity| schools| socioeconomic status| traffic|traffic density| air-pollution| los-angeles| environmental justice| ultrafine particles| childhood-cancer| major highway| children| asthma| health.	JAN-2004	air pollution| children's health| environmental justice| ethnicity| schools| socioeconomic status| traffic|traffic density| air-pollution| los-angeles| environmental justice| ultrafine particles| childhood-cancer| major highway| children| asthma| health	Green, RS; Smorodinsky, S; Kim, JJ; McLaughlin, R; Ostro, B	Proximity of California public schools to busy roads		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; children's health; environmental justice; ethnicity; schools; socioeconomic status; traffic	TRAFFIC DENSITY; AIR-POLLUTION; LOS-ANGELES; ENVIRONMENTAL JUSTICE; ULTRAFINE PARTICLES; CHILDHOOD-CANCER; MAJOR HIGHWAY; CHILDREN; ASTHMA; HEALTH	Residential proximity to busy roads has been associated with adverse health Outcomes, and school location may also be an important determinant of children's exposure to traffic-related pollutants. The goal of this study was to examine the characteristics of public schools (grades K-12) in California (n = 7,460) by proximity to major roads. We determined maximum daily traffic counts for all roads within 150 m of the school using a statewide road network and a geographic information system. Statewide, 173 schools (2.3%) with a total enrollment of 150,323 students were located within 150 m of high-traffic roads (greater than or equal to 50,000 vehides/day); 536 schools (7.2%) were within 150 m of medium-traffic roads (25,000-49,999 vehicles/day). Traffic exposure was related to race/ethnicity. For example, the overall percentage of nonwhite students was 78% at the schools located near high-traffic roads versus 60% at the schools with very low exposure (no streets with counted traffic data within 150 m). As the traffic exposure of schools increased, the percentage of both non-Hispanic black and Hispanic students attending the schools increased substantially. Traffic exposure was also related to school-based and census-tract-based socioeconomic indicators, including English language learners. The median percentage of children enrolled in free or reduced-price meal programs increased from 40.7% in the group with very low exposure to 60.5% in the highest exposure group. In summary, a substantial number of children in California attend schools dose to major roads with very high traffic counts, and a disproportionate number of those students are economically disadvantaged and nonwhite.	31	75	2004	6	10.1289/ehp.6566	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Reduced interferon gamma production and soluble CD14 levels in early life predict recurrent wheezing by 1 year of age. It is unknown whether reduced production of IFNgamma in early life, before any lower respiratory tract illness, is a risk factor for recurrent wheezing in infancy. We followed 238 infants prospectively from birth to I year of age. At birth and at 3 months of age, IFNgamma production from polyclonally stimulated peripheral blood mononuclear cells and soluble CD14 (sCD14) levels in plasma were measured. The odds of developing recurrent wheezing (assessed by questionnaire) in the first year of life were up to 4.5 times higher for children in the lowest quartile of IFNgamma production at 3 months (p = 0.0005) and 3.2 times higher for children in the lowest quartile of sCD14 levels at birth (p = 0.004) as compared with children in the other 3 combined quartiles of IFNgamma and sCD14, respectively. Findings were confirmed in the multivariate analysis. IFNgamma production at 3 months and sCD14 levels at birth were correlated (r = 0.188, p = 0.031). Our findings from a longitudinal cohort suggest that impaired IFNgamma production at 3 months and reduced plasmasCD14 levels at birth significantly increase the risk of developing recurrent wheezing in the first year of life.. wheezing| asthma| ifn gamma| cd14 antigen| lps receptor|respiratory syncytial virus| house-dust endotoxin| blood mononuclear-cells| day-care attendance| ifn-gamma| 1st year| peripheral-blood| risk factor| asthma| children.	JAN 1-2004	wheezing| asthma| ifn gamma| cd14 antigen| lps receptor|respiratory syncytial virus| house-dust endotoxin| blood mononuclear-cells| day-care attendance| ifn-gamma| 1st year| peripheral-blood| risk factor| asthma| children	Guerra, S; Lohman, IC; Halonen, M; Martinez, FD; Wright, AL	Reduced interferon gamma production and soluble CD14 levels in early life predict recurrent wheezing by 1 year of age		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	wheezing; asthma; IFN gamma; CD14 antigen; LPS receptor	RESPIRATORY SYNCYTIAL VIRUS; HOUSE-DUST ENDOTOXIN; BLOOD MONONUCLEAR-CELLS; DAY-CARE ATTENDANCE; IFN-GAMMA; 1ST YEAR; PERIPHERAL-BLOOD; RISK FACTOR; ASTHMA; CHILDREN	It is unknown whether reduced production of IFNgamma in early life, before any lower respiratory tract illness, is a risk factor for recurrent wheezing in infancy. We followed 238 infants prospectively from birth to I year of age. At birth and at 3 months of age, IFNgamma production from polyclonally stimulated peripheral blood mononuclear cells and soluble CD14 (sCD14) levels in plasma were measured. The odds of developing recurrent wheezing (assessed by questionnaire) in the first year of life were up to 4.5 times higher for children in the lowest quartile of IFNgamma production at 3 months (p = 0.0005) and 3.2 times higher for children in the lowest quartile of sCD14 levels at birth (p = 0.004) as compared with children in the other 3 combined quartiles of IFNgamma and sCD14, respectively. Findings were confirmed in the multivariate analysis. IFNgamma production at 3 months and sCD14 levels at birth were correlated (r = 0.188, p = 0.031). Our findings from a longitudinal cohort suggest that impaired IFNgamma production at 3 months and reduced plasmasCD14 levels at birth significantly increase the risk of developing recurrent wheezing in the first year of life.	37	75	2004	7	10.1164/rccm.200304-499OC	General & Internal Medicine; Respiratory System
"Scabies: New future for a neglected disease. Scabies is a disease of global proportions in both human and animal populations, resulting from infestation of the skin with the ""itch"" mite Sarcoptes scabiei. Despite the availability of effective chemotherapy the intensely itching lesions engender significant morbidity primarily due to secondary sepsis and post-infective complications. Some patients experience an extreme form of the disease, crusted scabies, in which many hundreds of mites may infest the skin causing severe crusting and hyperkeratosis. Overcrowded living conditions and poverty have been identified as significant confounding factors in transmission of the mite in humans. Control is hindered by difficulties with diagnosis, the cost of treatment, evidence for emerging resistance and lack of effective vaccines. Historically research on scabies has been extremely limited because of the difficulty in obtaining sufficient quantities of the organism. Recent molecular approaches have enabled considerable advances in the study of population genetics and transmission dynamics of S. scabiei. However, the most exciting and promising development is the potential exploitation of newly available data from S. scabiei cDNA libraries and EST projects. Ultimately this knowledge may aid early identification of disease, novel forms of chemotherapy, vaccine development and new treatment possibilities for this important but neglected parasite.. house-dust mite| crotamiton 10-percent cream| mitochondrial-dna sequences| crusted norwegian scabies| immunosorbent-assay elisa| treatment available soon| cdna expression library| group-iii allergen| tea-tree oil| sarcoptes-scabiei."	2004	house-dust mite| crotamiton 10-percent cream| mitochondrial-dna sequences| crusted norwegian scabies| immunosorbent-assay elisa| treatment available soon| cdna expression library| group-iii allergen| tea-tree oil| sarcoptes-scabiei	Walton, SF; Holt, DC; Currie, BJ; Kemp, DJ	Scabies: New future for a neglected disease		ADVANCES IN PARASITOLOGY, VOL 57		HOUSE-DUST MITE; CROTAMITON 10-PERCENT CREAM; MITOCHONDRIAL-DNA SEQUENCES; CRUSTED NORWEGIAN SCABIES; IMMUNOSORBENT-ASSAY ELISA; TREATMENT AVAILABLE SOON; CDNA EXPRESSION LIBRARY; GROUP-III ALLERGEN; TEA-TREE OIL; SARCOPTES-SCABIEI	"Scabies is a disease of global proportions in both human and animal populations, resulting from infestation of the skin with the ""itch"" mite Sarcoptes scabiei. Despite the availability of effective chemotherapy the intensely itching lesions engender significant morbidity primarily due to secondary sepsis and post-infective complications. Some patients experience an extreme form of the disease, crusted scabies, in which many hundreds of mites may infest the skin causing severe crusting and hyperkeratosis. Overcrowded living conditions and poverty have been identified as significant confounding factors in transmission of the mite in humans. Control is hindered by difficulties with diagnosis, the cost of treatment, evidence for emerging resistance and lack of effective vaccines. Historically research on scabies has been extremely limited because of the difficulty in obtaining sufficient quantities of the organism. Recent molecular approaches have enabled considerable advances in the study of population genetics and transmission dynamics of S. scabiei. However, the most exciting and promising development is the potential exploitation of newly available data from S. scabiei cDNA libraries and EST projects. Ultimately this knowledge may aid early identification of disease, novel forms of chemotherapy, vaccine development and new treatment possibilities for this important but neglected parasite."	231	75	2004	68	10.1016/S0065-308X(04)57005-7	Parasitology
Accelerated airway dendritic cell maturation, trafficking, and elimination in a mouse model of asthma. Pulmonary dendritic cells (DC) can induce both tolerogenic as well as inflammatory immune responses in the lung. Conversely, little is known about the impact of ongoing airway inflammation on pulmonary DC biology. In noninflammatory conditions, expression of T cell costimulatory molecules on mouse airway DCs is low and only upregulated after homing into draining thoracic lymph nodes. In this study, we reveal that ongoing allergic airway inflammation induces a premature upregulation of the T cell costimulatory molecules CD40, B7-2 and intercellular adhesion molecule 1 on DCs still present in the airways. In contrast, high surface expression of inducible costimulator ligand, involved in respiratory tolerance induction is restricted to DCs from noninflamed lungs. In addition, during inflammation the migratory flux of allergen-transporting airway DCs toward draining thoracic nodes increases both in amplitude as well as in speed. Remarkably, migratory DCs from inflamed airways are short-lived in the draining lymph nodes, a finding that is temporally associated with a marked loss of the antiapoptotic protein Bcl-2 in these cells. This study demonstrates the profound effects of ongoing allergen-driven airway inflammation on the dynamics of pulmonary DC physiology, a knowledge that could be exploited in the development of novel DC-based immunotherapies.. necrosis-factor-alpha| cd4(+) t-cells| inhaled antigen| class-ii| in-vivo| icos| inflammation| responses| mice| apoptosis.	SEP-2003	necrosis-factor-alpha| cd4(+) t-cells| inhaled antigen| class-ii| in-vivo| icos| inflammation| responses| mice| apoptosis	Vermaelen, K; Pauwels, R	Accelerated airway dendritic cell maturation, trafficking, and elimination in a mouse model of asthma		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		NECROSIS-FACTOR-ALPHA; CD4(+) T-CELLS; INHALED ANTIGEN; CLASS-II; IN-VIVO; ICOS; INFLAMMATION; RESPONSES; MICE; APOPTOSIS	Pulmonary dendritic cells (DC) can induce both tolerogenic as well as inflammatory immune responses in the lung. Conversely, little is known about the impact of ongoing airway inflammation on pulmonary DC biology. In noninflammatory conditions, expression of T cell costimulatory molecules on mouse airway DCs is low and only upregulated after homing into draining thoracic lymph nodes. In this study, we reveal that ongoing allergic airway inflammation induces a premature upregulation of the T cell costimulatory molecules CD40, B7-2 and intercellular adhesion molecule 1 on DCs still present in the airways. In contrast, high surface expression of inducible costimulator ligand, involved in respiratory tolerance induction is restricted to DCs from noninflamed lungs. In addition, during inflammation the migratory flux of allergen-transporting airway DCs toward draining thoracic nodes increases both in amplitude as well as in speed. Remarkably, migratory DCs from inflamed airways are short-lived in the draining lymph nodes, a finding that is temporally associated with a marked loss of the antiapoptotic protein Bcl-2 in these cells. This study demonstrates the profound effects of ongoing allergen-driven airway inflammation on the dynamics of pulmonary DC physiology, a knowledge that could be exploited in the development of novel DC-based immunotherapies.	30	75	2003	5	10.1165/rcmb.2003-0008OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Climate, traffic-related air pollutants and allergic rhinitis prevalence in middle-school children in Taiwan. The prevalence of allergic rhinitis, a common respiratory disorder, may be rapidly increasing. Epidemiological studies, however, indicate little about its association with climatic factors and air pollution. The relationship between traffic-related air pollutants and allergic rhinitis in middle-school students was therefore investigated. In a nationwide survey of middle-school students in Taiwan conducted in 1995/1996, the lifetime prevalence of physician-diagnosed allergic rhinitis and typical symptoms of allergic rhinitis were compared with air-monitoring station data on temperature, relative humidity, sulphur dioxide (SO2), nitrogen oxides (NOx), ozone (03), carbon monoxide (CO) and particulate matter with a 50% cut-off aerodynamic diameter of 10 PM (PM10). A total of 331,686 nonsmoking children attended schools located within 2 km of 55 stations. Mean (range) annual exposures were: CO 853 (381-1,610) parts per billion (ppb), NOx 35.1 (10.2-72.4) ppb, SO2 7.57 (0.88-21.2) ppb, PM10 69.2 (40.1-116.2) mug.m(-3), O-3 21.3 (12.4-34.1) ppb, temperature 22.9 (19.6-25.1)degreesC, and relative humidity 76.2 (64.8-86.2)%. The prevalence of physician-diagnosed allergic rhinitis was 28.6 and 19.5% in males and females, respectively, with prevalence of questionnaire-determined allergic rhinitis 42.4 and 34.0%. After adjustment for age, parental education and history of atopic eczema, physician-diagnosed allergic rhinitis was found to be associated with higher nonsummer (September-May) warmth and traffic-related air pollutants, including CO, NOx and O-3. Questionnaire-determined allergic rhinitis correlated only with traffic-related air pollutants. Nonsummer warmth and traffic-related air pollution, probably mediated through exposure to common allergens such as dust mites, are possible risk factors for allergic rhinitis in middle-school-aged children.. air pollution| allergic rhinitis| children| climate| factor analysis|respiratory health| subtropical climate| nitrogen-dioxide| hay-fever| asthma| symptoms| epidemiology| atopy| pollution| exposure.	JUN-2003	air pollution| allergic rhinitis| children| climate| factor analysis|respiratory health| subtropical climate| nitrogen-dioxide| hay-fever| asthma| symptoms| epidemiology| atopy| pollution| exposure	Lee, YL; Shaw, CK; Su, HJ; Lai, JS; Ko, YC; Huang, SL; Sung, FC; Guo, YL	Climate, traffic-related air pollutants and allergic rhinitis prevalence in middle-school children in Taiwan		EUROPEAN RESPIRATORY JOURNAL	air pollution; allergic rhinitis; children; climate; factor analysis	RESPIRATORY HEALTH; SUBTROPICAL CLIMATE; NITROGEN-DIOXIDE; HAY-FEVER; ASTHMA; SYMPTOMS; EPIDEMIOLOGY; ATOPY; POLLUTION; EXPOSURE	The prevalence of allergic rhinitis, a common respiratory disorder, may be rapidly increasing. Epidemiological studies, however, indicate little about its association with climatic factors and air pollution. The relationship between traffic-related air pollutants and allergic rhinitis in middle-school students was therefore investigated. In a nationwide survey of middle-school students in Taiwan conducted in 1995/1996, the lifetime prevalence of physician-diagnosed allergic rhinitis and typical symptoms of allergic rhinitis were compared with air-monitoring station data on temperature, relative humidity, sulphur dioxide (SO2), nitrogen oxides (NOx), ozone (03), carbon monoxide (CO) and particulate matter with a 50% cut-off aerodynamic diameter of 10 PM (PM10). A total of 331,686 nonsmoking children attended schools located within 2 km of 55 stations. Mean (range) annual exposures were: CO 853 (381-1,610) parts per billion (ppb), NOx 35.1 (10.2-72.4) ppb, SO2 7.57 (0.88-21.2) ppb, PM10 69.2 (40.1-116.2) mug.m(-3), O-3 21.3 (12.4-34.1) ppb, temperature 22.9 (19.6-25.1)degreesC, and relative humidity 76.2 (64.8-86.2)%. The prevalence of physician-diagnosed allergic rhinitis was 28.6 and 19.5% in males and females, respectively, with prevalence of questionnaire-determined allergic rhinitis 42.4 and 34.0%. After adjustment for age, parental education and history of atopic eczema, physician-diagnosed allergic rhinitis was found to be associated with higher nonsummer (September-May) warmth and traffic-related air pollutants, including CO, NOx and O-3. Questionnaire-determined allergic rhinitis correlated only with traffic-related air pollutants. Nonsummer warmth and traffic-related air pollution, probably mediated through exposure to common allergens such as dust mites, are possible risk factors for allergic rhinitis in middle-school-aged children.	47	75	2003	7	10.1183/09031936.03.00094602	Respiratory System
Short-term variation in air quality associated with firework events: A case study. The effect of fireworks on air quality as assessed from the ambient concentrations of various air pollutants (SO2, NO2, PM10 and TSP) during Diwali festival in Hisar city (India). in November 1999, The extensive use of fireworks as found to be related to short-term variation in air quality. During the festival the concentration of SO2 was observed to be increased similar to 10-fold at few sites. whereas the concentrations of NO2, PM10 and TSP increased 2-3 times. compared to the data collected on a typical winter day in December 1999. The maximum NO2 concentration was observed a day after the festival. The diurnal pattern of the above pollutants showed a slight increase in the night. The levels of these Pollutants observed during Diwali were found to be moderately high, which can be associated with. serious health impacts.. sulfur-dioxide| ambient air| hospital admissions| daily mortality| lung-function| pollution| exposure| children| birmingham| asthma.	APR-2003	sulfur-dioxide| ambient air| hospital admissions| daily mortality| lung-function| pollution| exposure| children| birmingham| asthma	Ravindra, K; Mor, S; Kaushik, CP	Short-term variation in air quality associated with firework events: A case study		JOURNAL OF ENVIRONMENTAL MONITORING		SULFUR-DIOXIDE; AMBIENT AIR; HOSPITAL ADMISSIONS; DAILY MORTALITY; LUNG-FUNCTION; POLLUTION; EXPOSURE; CHILDREN; BIRMINGHAM; ASTHMA	The effect of fireworks on air quality as assessed from the ambient concentrations of various air pollutants (SO2, NO2, PM10 and TSP) during Diwali festival in Hisar city (India). in November 1999, The extensive use of fireworks as found to be related to short-term variation in air quality. During the festival the concentration of SO2 was observed to be increased similar to 10-fold at few sites. whereas the concentrations of NO2, PM10 and TSP increased 2-3 times. compared to the data collected on a typical winter day in December 1999. The maximum NO2 concentration was observed a day after the festival. The diurnal pattern of the above pollutants showed a slight increase in the night. The levels of these Pollutants observed during Diwali were found to be moderately high, which can be associated with. serious health impacts.	42	75	2003	5	10.1039/b211943a	Chemistry; Environmental Sciences & Ecology
Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line. It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34 + hematopoietic progenitor cells (CD34 + HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-l. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a dose-dependent manner while non-sensitizers, such as SLS and methyl salicylate (MS), did not. To note, the metal allergens such as (NH4)(2)[PtCl4], NiSO4 and CoSO4 augmented significantly only CD54 expression. Taking advantage of a cultured cell line, measurement of the co-stimulatory molecules, CD54 and CD86, on naive THP-1 cells following chemical exposure shows promise for the development of a simple, short-term in vitro sensitization test. (C) 2003 Elsevier Science Ltd. All rights reserved.. cd54| cd86| thp-1 cell line| in vitro sensitization test|epidermal langerhans cells| vitro primary sensitization| human dendritic cells| in-vitro| t-cells| contact sensitivity| messenger-rna| haptens| phenotype| induction.	APR-2003	cd54| cd86| thp-1 cell line| in vitro sensitization test|epidermal langerhans cells| vitro primary sensitization| human dendritic cells| in-vitro| t-cells| contact sensitivity| messenger-rna| haptens| phenotype| induction	Yoshida, Y; Sakaguchi, H; Ito, Y; Okuda, M; Suzuki, H	Evaluation of the skin sensitization potential of chemicals using expression of co-stimulatory molecules, CD54 and CD86, on the naive THP-1 cell line		TOXICOLOGY IN VITRO	CD54; CD86; THP-1 cell line; in vitro sensitization test	EPIDERMAL LANGERHANS CELLS; VITRO PRIMARY SENSITIZATION; HUMAN DENDRITIC CELLS; IN-VITRO; T-CELLS; CONTACT SENSITIVITY; MESSENGER-RNA; HAPTENS; PHENOTYPE; INDUCTION	It has been known that dendritic cells (DCs) including Langerhans cells (LCs) play a critical role in the skin sensitization process. Many attempts have been made to develop in vitro sensitization tests that employ DCs derived from peripheral blood mononuclear cells (PBMC-DC) or CD34 + hematopoietic progenitor cells (CD34 + HPC) purified from cord blood or bone marrow. However, the use of the DCs in in vitro methods has been difficult due to the nature of these cells such as low levels in the source and/or donor-to-donor variability. In our studies, we employed the human monocytic leukemia cell line, THP-1, in order to avoid some of these difficulties. At the start, we examined whether treatment of the cells with various cytokines could produce DCs from THP-1. Treatment of THP-1 cells with cytokines such as GM-CSF, IL-4, TNF-alpha, and/or PMA did induce some phenotypic changes in THP-1 cells that were characteristic of DCs. Subsequently, responses to a known sensitizer, dinitrochlorobenzene (DNCB), and a non-sensitizer, dimethyl sulfoxide (DMSO) or sodium lauryl sulfate (SLS), on the expression of co-stimulatory molecules, CD54 and CD86, were examined between the naive cells and the cytokine-treated cells. Interestingly, the naive THP-1 cells responded only to DNCB and the response to the sensitizer was more distinct than cytokine-treated THP-1 cells. Similar phenomena were also observed in the human myeloid leukemia cell line, KG-l. Furthermore, with treatment of DNCB, naive THP-1 cells showed augmented expression of HLA, CD80 and secretion of IL-1beta. The response of THP-1 cells to a sensitizer was similar to that of LCs/DCs. Upon demonstrating the differentiation of monocyte cells in our system, we then evaluated a series of chemicals, including known sensitizers and non-sensitizers, for their potential to augment CD54 and CD86 expression on naive THP-1 cells. Indeed, known sensitizers such as PPD and 2-MBT significantly augmented CD54 and CD86 expression in a dose-dependent manner while non-sensitizers, such as SLS and methyl salicylate (MS), did not. To note, the metal allergens such as (NH4)(2)[PtCl4], NiSO4 and CoSO4 augmented significantly only CD54 expression. Taking advantage of a cultured cell line, measurement of the co-stimulatory molecules, CD54 and CD86, on naive THP-1 cells following chemical exposure shows promise for the development of a simple, short-term in vitro sensitization test. (C) 2003 Elsevier Science Ltd. All rights reserved.	24	75	2003	8	10.1016/S0887-2333(03)00006-7	Toxicology
Endotoxin levels in Estonian and Swedish house dust and atopy in infancy. Background Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1-stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation. Aim To relate the endotoxin levels in house dust from two countries with a low (Estonia) and a high (Sweden) prevalence of allergy to the development of atopic disease and sensitization in the children during the first 2 years of life. Methods The study included 108 children from Tartu, Estonia and 111 children from Linkoping, Sweden. Skin prick tests were performed at 3, 6, 12 and 24 months of age, and questionnaires were distributed to the families. At 24 months, a paediatrician examined the children. Dust samples were collected from mattresses and carpets and the endotoxin concentration was determined by a chromogenic Limulus assay. Results The endotoxin levels were higher in Estonian than in Swedish house dust (median levels 29 (range 0.25-280) and 14 (range 0.25-99) EU/mg dust, respectively, P < 0.001). Furthermore, the levels were inversely related to the development of atopic disease and sensitization in the Swedish, but not in the Estonian, children. Conclusions The low prevalence of atopic disease in Estonia may, at least in part, be related to the high endotoxin levels in this country. The findings support that high levels of endotoxin, or other bacterial products with Th1-stimulating properties, might protect children from developing atopic disease.. atopy| childhood| endotoxin|hay-fever| bacterial lipopolysaccharide| allergic sensitization| respiratory symptoms| cell-development| asthma| exposure| prevalence| children| eczema.	MAR-2003	atopy| childhood| endotoxin|hay-fever| bacterial lipopolysaccharide| allergic sensitization| respiratory symptoms| cell-development| asthma| exposure| prevalence| children| eczema	Bottcher, MF; Bjorksten, B; Gustafson, S; Voor, T; Jenmalm, MC	Endotoxin levels in Estonian and Swedish house dust and atopy in infancy		CLINICAL AND EXPERIMENTAL ALLERGY	atopy; childhood; endotoxin	HAY-FEVER; BACTERIAL LIPOPOLYSACCHARIDE; ALLERGIC SENSITIZATION; RESPIRATORY SYMPTOMS; CELL-DEVELOPMENT; ASTHMA; EXPOSURE; PREVALENCE; CHILDREN; ECZEMA	Background Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1-stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation. Aim To relate the endotoxin levels in house dust from two countries with a low (Estonia) and a high (Sweden) prevalence of allergy to the development of atopic disease and sensitization in the children during the first 2 years of life. Methods The study included 108 children from Tartu, Estonia and 111 children from Linkoping, Sweden. Skin prick tests were performed at 3, 6, 12 and 24 months of age, and questionnaires were distributed to the families. At 24 months, a paediatrician examined the children. Dust samples were collected from mattresses and carpets and the endotoxin concentration was determined by a chromogenic Limulus assay. Results The endotoxin levels were higher in Estonian than in Swedish house dust (median levels 29 (range 0.25-280) and 14 (range 0.25-99) EU/mg dust, respectively, P < 0.001). Furthermore, the levels were inversely related to the development of atopic disease and sensitization in the Swedish, but not in the Estonian, children. Conclusions The low prevalence of atopic disease in Estonia may, at least in part, be related to the high endotoxin levels in this country. The findings support that high levels of endotoxin, or other bacterial products with Th1-stimulating properties, might protect children from developing atopic disease.	32	75	2003	6	10.1046/j.1365-2222.2003.01562.x	Allergy; Immunology
Asthma management and environmental tobacco smoke exposure reduction in Latino children: A controlled trial. Objectives. This study tested the efficacy of coaching to reduce environmental tobacco smoke (ETS) exposure among asthmatic Latino children. Design. After asthma management education, families were randomly assigned to no additional service (control condition) or to coaching for ETS exposure reduction (experimental condition). Setting. The study was conducted in San Diego, California. Participants. Two hundred four Latino children (ages 3-17 years) with asthma participated. Intervention. Approximately 1.5 hours of asthma management education was provided; experimental families also obtained 7 coaching sessions (similar to45 minutes each) to reduce ETS exposure. Outcome Measures. Reported ETS exposure and children's urine cotinine were measured. Results. Parents in the coached condition reported their children exposed to significantly fewer cigarettes than parents of control children by 4 months (postcoaching). Reported prevalence of exposed children decreased to 52% for the coached families, but only to 69% for controls. By month 4, mean cotinine levels decreased among coached and increased among control children. Cotinine prevalence decreased from 54% to 40% among coached families, while it increased from 43% to 49% among controls. However, cotinine levels decreased among controls to the same level achieved by coached families by the 13-month follow-up. Conclusions. Asthma management education plus coaching can reduce ETS exposure more than expected from education alone, and decreases in the coached condition may be sustained for about a year. The delayed decrease in cotinine among controls is discussed.. environmental tobacco smoke| passive smoking| coaching| latino| women| children| asthma| cotinine|passive smoking| socioeconomic-factors| young-children| reliability| cotinine| income| california| validity| health| hospitalization.	NOV-2002	environmental tobacco smoke| passive smoking| coaching| latino| women| children| asthma| cotinine|passive smoking| socioeconomic-factors| young-children| reliability| cotinine| income| california| validity| health| hospitalization	Hovell, MF; Meltzer, SB; Wahlgren, DR; Matt, GE; Hofstetter, R; Jones, JA; Meltzer, EO; Bernert, JT; Pirkle, JL	Asthma management and environmental tobacco smoke exposure reduction in Latino children: A controlled trial		PEDIATRICS	environmental tobacco smoke; passive smoking; coaching; Latino; women; children; asthma; cotinine	PASSIVE SMOKING; SOCIOECONOMIC-FACTORS; YOUNG-CHILDREN; RELIABILITY; COTININE; INCOME; CALIFORNIA; VALIDITY; HEALTH; HOSPITALIZATION	Objectives. This study tested the efficacy of coaching to reduce environmental tobacco smoke (ETS) exposure among asthmatic Latino children. Design. After asthma management education, families were randomly assigned to no additional service (control condition) or to coaching for ETS exposure reduction (experimental condition). Setting. The study was conducted in San Diego, California. Participants. Two hundred four Latino children (ages 3-17 years) with asthma participated. Intervention. Approximately 1.5 hours of asthma management education was provided; experimental families also obtained 7 coaching sessions (similar to45 minutes each) to reduce ETS exposure. Outcome Measures. Reported ETS exposure and children's urine cotinine were measured. Results. Parents in the coached condition reported their children exposed to significantly fewer cigarettes than parents of control children by 4 months (postcoaching). Reported prevalence of exposed children decreased to 52% for the coached families, but only to 69% for controls. By month 4, mean cotinine levels decreased among coached and increased among control children. Cotinine prevalence decreased from 54% to 40% among coached families, while it increased from 43% to 49% among controls. However, cotinine levels decreased among controls to the same level achieved by coached families by the 13-month follow-up. Conclusions. Asthma management education plus coaching can reduce ETS exposure more than expected from education alone, and decreases in the coached condition may be sustained for about a year. The delayed decrease in cotinine among controls is discussed.	68	75	2002	11	10.1542/peds.110.5.946	Pediatrics
Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test efficiency than specific antibodies for identification of diisocyanate asthma. We previously reported that diisocyanate-human serum albumin (DIISO-HSA) stimulated production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells is significantly associated with a clinical diagnosis of diisocyanate asthma (DA). Others have reported that antibodies for DIISO-HSA are specific but insensitive markers of DA. This study was performed to evaluate test characteristics of the in vitro MCP-1 assay compared with DIISO-HSA-specific immunoglobulin (Ig) G and IgE in identifying workers with DA. MCPA was quantitated in peripheral blood mononuclear cell supernatants 48 hours after incubation with DIISO-HSA antigens. Assay results were compared with outcomes of specific inhalation challenge (SIC) testing. Nineteen of 54 (35%) workers assayed for antibodies and MCPA stimulation had SIC-confirmed DA. Mean MCP-1 produced by SIC-positive workers was greater than SIC-negative workers (p less than or equal to 0.001). Diagnostic sensitivity, specificity, and test efficiency for specific IgG were 47%, 74%, and 65%, respectively, and for specific IgE were 21%, 89%, and 65%, respectively. Sensitivity, specificity, and test efficiency of the MCPA test were 79%, 91%, and 87%, respectively. This study indicates that the MCP-1 stimulation assay has greater sensitivity and specificity than the specific antibody assays in correctly identifying DA.. occupational asthma| diisocyanate| mcp-1| antibody|histamine-releasing factors| induced occupational asthma| human serum-albumin| hexamethylene diisocyanate| diphenylmethane diisocyanate| immune-responses| exposure| isocyanates| workers| reactivity.	AUG 15-2002	occupational asthma| diisocyanate| mcp-1| antibody|histamine-releasing factors| induced occupational asthma| human serum-albumin| hexamethylene diisocyanate| diphenylmethane diisocyanate| immune-responses| exposure| isocyanates| workers| reactivity	Bernstein, DI; Cartier, A; Cote, J; Malo, JL; Boulet, LP; Wanner, M; Milot, J; L'Archeveque, J; Trudeau, C; Lummus, Z	Diisocyanate antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test efficiency than specific antibodies for identification of diisocyanate asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	occupational asthma; diisocyanate; MCP-1; antibody	HISTAMINE-RELEASING FACTORS; INDUCED OCCUPATIONAL ASTHMA; HUMAN SERUM-ALBUMIN; HEXAMETHYLENE DIISOCYANATE; DIPHENYLMETHANE DIISOCYANATE; IMMUNE-RESPONSES; EXPOSURE; ISOCYANATES; WORKERS; REACTIVITY	We previously reported that diisocyanate-human serum albumin (DIISO-HSA) stimulated production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells is significantly associated with a clinical diagnosis of diisocyanate asthma (DA). Others have reported that antibodies for DIISO-HSA are specific but insensitive markers of DA. This study was performed to evaluate test characteristics of the in vitro MCP-1 assay compared with DIISO-HSA-specific immunoglobulin (Ig) G and IgE in identifying workers with DA. MCPA was quantitated in peripheral blood mononuclear cell supernatants 48 hours after incubation with DIISO-HSA antigens. Assay results were compared with outcomes of specific inhalation challenge (SIC) testing. Nineteen of 54 (35%) workers assayed for antibodies and MCPA stimulation had SIC-confirmed DA. Mean MCP-1 produced by SIC-positive workers was greater than SIC-negative workers (p less than or equal to 0.001). Diagnostic sensitivity, specificity, and test efficiency for specific IgG were 47%, 74%, and 65%, respectively, and for specific IgE were 21%, 89%, and 65%, respectively. Sensitivity, specificity, and test efficiency of the MCPA test were 79%, 91%, and 87%, respectively. This study indicates that the MCP-1 stimulation assay has greater sensitivity and specificity than the specific antibody assays in correctly identifying DA.	30	75	2002	6	10.1164/rccm.2109018	General & Internal Medicine; Respiratory System
Risk factors for hospital admission for asthma from childhood to young adulthood: A longitudinal population study. Background: Predictors of hospital admissions for asthma in children and young adults in a general population are not well defined, because most studies have used selected subpopulations. Objective: The purpose of this investigation was to determine risk factors for single and multiple hospital admissions for asthma. Methods: The members of a population-based, unselected birth cohort of 1037 New Zealanders answered questionnaires and underwent lung function, airway responsiveness, and allergy testing on 7 occasions to the age of 26 years. Results: Among the 766 study members (74% of the cohort) who reported wheezing symptoms ever by the age of 26 years, 136 hospitalizations were reported by 62 individuals (8.3% of those at risk, 6.2% of the total cohort). Only 55 of these 136 admissions involved children less than 9 years of age; admissions continued to occur between the ages of 9 and 18 years (40 admissions) and at >18 years (41 admissions). Those admitted were predominantly male, had earlier ages of onset of symptoms, were more atopic, and had more airway hyperresponsiveness to methacholine than those not admitted. Frequent symptoms and low lung function were evident among the 45 study members with single admissions and even more evident among the 17 study members with multiple (2-10) admissions. Conclusions: A surprisingly large fraction of this unselected population experienced hospitalization for asthma during the 26-year follow-up, many being admitted in later childhood, adolescence, and early adulthood. Clinical characteristics and markers of severity, including frequent respiratory symptoms, airway hyperresponsiveness, atopy, and low lung function, identify those at high risk for hospitalization for asthma, particularly with respect to multiple admissions.. asthma| hospital admission| risk factors| allergy| longitudinal population study| epidemiology|house-dust mite| bronchial hyperresponsiveness| indoor allergens| economic burden| school absence| children| emergency| sensitization| prevalence| exposure.	AUG-2002	asthma| hospital admission| risk factors| allergy| longitudinal population study| epidemiology|house-dust mite| bronchial hyperresponsiveness| indoor allergens| economic burden| school absence| children| emergency| sensitization| prevalence| exposure	Rasmussen, F; Taylor, DR; Flanneryb, EM; Cowan, JO; Greene, JM; Herbison, GP; Sears, MR	Risk factors for hospital admission for asthma from childhood to young adulthood: A longitudinal population study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; hospital admission; risk factors; allergy; longitudinal population study; epidemiology	HOUSE-DUST MITE; BRONCHIAL HYPERRESPONSIVENESS; INDOOR ALLERGENS; ECONOMIC BURDEN; SCHOOL ABSENCE; CHILDREN; EMERGENCY; SENSITIZATION; PREVALENCE; EXPOSURE	Background: Predictors of hospital admissions for asthma in children and young adults in a general population are not well defined, because most studies have used selected subpopulations. Objective: The purpose of this investigation was to determine risk factors for single and multiple hospital admissions for asthma. Methods: The members of a population-based, unselected birth cohort of 1037 New Zealanders answered questionnaires and underwent lung function, airway responsiveness, and allergy testing on 7 occasions to the age of 26 years. Results: Among the 766 study members (74% of the cohort) who reported wheezing symptoms ever by the age of 26 years, 136 hospitalizations were reported by 62 individuals (8.3% of those at risk, 6.2% of the total cohort). Only 55 of these 136 admissions involved children less than 9 years of age; admissions continued to occur between the ages of 9 and 18 years (40 admissions) and at >18 years (41 admissions). Those admitted were predominantly male, had earlier ages of onset of symptoms, were more atopic, and had more airway hyperresponsiveness to methacholine than those not admitted. Frequent symptoms and low lung function were evident among the 45 study members with single admissions and even more evident among the 17 study members with multiple (2-10) admissions. Conclusions: A surprisingly large fraction of this unselected population experienced hospitalization for asthma during the 26-year follow-up, many being admitted in later childhood, adolescence, and early adulthood. Clinical characteristics and markers of severity, including frequent respiratory symptoms, airway hyperresponsiveness, atopy, and low lung function, identify those at high risk for hospitalization for asthma, particularly with respect to multiple admissions.	37	75	2002	8	10.1067/mai.2002.125295	Allergy; Immunology
Risk factors for developing systemic lupus erythematosus: a case-control study in southern Sweden. Objective. To explore the risk factors that have been suggested to be associated with the development of SLE. Methods. A case-control study was performed and a questionnaire was developed to obtain the data. Consecutive female incident cases diagnosed between 1981 and 1999 in a defined,geographical area in southern Sweden were included. Controls, matched for calendar year of birth, were selected randomly from the same area. In total, 85 cases and 205 controls agreed to participate. The questionnaire included questions about formal education, body weight and height, medical history, family history of autoimmune diseases, exposure to ultraviolet radiation, animals, hair-colouring dyes, alfalfa (lucerne) sprouts, smoking and alcohol habits, history of physical traumata, blood transfusion, silicone breast implants, exogenous oestrogens, other medication, and significant negative life events. Results. Using a multivariate model, a history of hypertension [odds ratio (OR)=3.7, 95% confidence interval (CI) 1.4-9.8], drug allergy (OR=3.6, 95% CI 1.4-9.5), a type I/II sun-reactive Skin type (OR=2.3, 95% CI 1.1-4.8) and a family history of SLE (OR=6.8, 95% CI 1.4-32) were all significantly associated with an increased risk of developing SLE, whereas consumption of alcohol was inversely associated with the risk of SLE (use of alcohol very seldom, OR=1.0; 1-150 g/month, OR=0.4, 95% CI 0.2-1.0; > 150 g/month, OR=0.2, 95% CI 0.1-0.5). A suggested association with increased SLE risk was seen for smoking (OR=1.8, 95% CI 0.9-3.6) and blood transfusions (OR=23, 95% CI 0.9-5.8). Neither exposure to exogenous oestrogen nor exposure to hair-colouring dyes was associated with SLE. Conclusions. Risk factors of both exogenous and endogenous origin were identified in this population-based series of SLE patients.. sle| risk factors| smoking| alcohol| drug allergy| hypertension| family history|oral-contraceptives| defined population| disease| history| therapy| stress.	MAY-2002	sle| risk factors| smoking| alcohol| drug allergy| hypertension| family history|oral-contraceptives| defined population| disease| history| therapy| stress	Bengtsson, AA; Rylander, L; Hagmar, L; Nived, O; Sturfelt, G	Risk factors for developing systemic lupus erythematosus: a case-control study in southern Sweden		RHEUMATOLOGY	SLE; risk factors; smoking; alcohol; drug allergy; hypertension; family history	ORAL-CONTRACEPTIVES; DEFINED POPULATION; DISEASE; HISTORY; THERAPY; STRESS	Objective. To explore the risk factors that have been suggested to be associated with the development of SLE. Methods. A case-control study was performed and a questionnaire was developed to obtain the data. Consecutive female incident cases diagnosed between 1981 and 1999 in a defined,geographical area in southern Sweden were included. Controls, matched for calendar year of birth, were selected randomly from the same area. In total, 85 cases and 205 controls agreed to participate. The questionnaire included questions about formal education, body weight and height, medical history, family history of autoimmune diseases, exposure to ultraviolet radiation, animals, hair-colouring dyes, alfalfa (lucerne) sprouts, smoking and alcohol habits, history of physical traumata, blood transfusion, silicone breast implants, exogenous oestrogens, other medication, and significant negative life events. Results. Using a multivariate model, a history of hypertension [odds ratio (OR)=3.7, 95% confidence interval (CI) 1.4-9.8], drug allergy (OR=3.6, 95% CI 1.4-9.5), a type I/II sun-reactive Skin type (OR=2.3, 95% CI 1.1-4.8) and a family history of SLE (OR=6.8, 95% CI 1.4-32) were all significantly associated with an increased risk of developing SLE, whereas consumption of alcohol was inversely associated with the risk of SLE (use of alcohol very seldom, OR=1.0; 1-150 g/month, OR=0.4, 95% CI 0.2-1.0; > 150 g/month, OR=0.2, 95% CI 0.1-0.5). A suggested association with increased SLE risk was seen for smoking (OR=1.8, 95% CI 0.9-3.6) and blood transfusions (OR=23, 95% CI 0.9-5.8). Neither exposure to exogenous oestrogen nor exposure to hair-colouring dyes was associated with SLE. Conclusions. Risk factors of both exogenous and endogenous origin were identified in this population-based series of SLE patients.	36	75	2002	9	10.1093/rheumatology/41.5.563	Rheumatology
Increase of allergen-specific immunoglobulin E antibodies from 1973 to 1994 in a Finnish population and a possible relationship to Helicobacter pylori infections. Background The prevalence of atopic diseases - hayfever, asthma and eczema - has increased over the past decades. The increase may be associated with decreased rates of infections such as measles., hepatitis A, tuberculosis, toxoplasmosis, and, as recently suggested, Helicobacter pylori gastritis. Objective Since the increase of atopy has been mainly based on clinical studies. we wanted to study the prevalence of allergen-specific Immunoglobulin (Ig)E antibodies in two cross-sectional, adult population-based serum samples two decades apart. Since the sera had been tested for H. pylori antibodies, we also had a chance to look for a possible relationship between these two findings. Methods We determined the prevalence rate of allergen-specific serum IgE antibodies against birch and timothy pollen, and cat and dog epithelium allergens by the radioallergosorbent test in a 15-54-years-old Finnish population using 326 sera collected in 1973 and 319 sera collected in 1994 from randomly selected subjects. Results From 1973 to 1994 allergen-specific IgE prevalence rates and IgE antibody levels rose. In 1994, the prevalence rate of positive findings in 15-24-year-old population had increased from I I to 38% (3.5-fold increase, P=0.0001, OR 5.12, Cl 95% 2.32-11.3). In older 10-year age groups similar trends did not reach significance, but the overall change was significant with all three cut-off levels of allergen-specific IgE analysed. The percentage of IgE-positive persons rose mainly in the subgroup with no H. pylori antibodies. In 1994 21% of the H. pylori-negative subjects had IgE antibodies compared with 5% of the H. pylori-positive subjects (in 1973 11% in both subgroups). Conclusions IgE-based evidence for an increase in IgE-mediated allergy was uncovered. The increase occurred mainly in the subgroup with no antibodies to H. pylori, which support the hypothesis that H, pylori could be one of the microbes counteracting atopy.. allergy| allergen-specific ige| atopy| helicobacter pylori antibodies| prevalence rates|adult-population| atopy| ige| prevalence| children| asthma| vaccination| adolescents| exposure| cohort.	MAR-2002	allergy| allergen-specific ige| atopy| helicobacter pylori antibodies| prevalence rates|adult-population| atopy| ige| prevalence| children| asthma| vaccination| adolescents| exposure| cohort	Kosunen, TU; Hook-Nikanne, J; Salomaa, A; Sarna, S; Aromaa, A; Haahtela, T	Increase of allergen-specific immunoglobulin E antibodies from 1973 to 1994 in a Finnish population and a possible relationship to Helicobacter pylori infections		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; allergen-specific IgE; atopy; Helicobacter pylori antibodies; prevalence rates	ADULT-POPULATION; ATOPY; IGE; PREVALENCE; CHILDREN; ASTHMA; VACCINATION; ADOLESCENTS; EXPOSURE; COHORT	Background The prevalence of atopic diseases - hayfever, asthma and eczema - has increased over the past decades. The increase may be associated with decreased rates of infections such as measles., hepatitis A, tuberculosis, toxoplasmosis, and, as recently suggested, Helicobacter pylori gastritis. Objective Since the increase of atopy has been mainly based on clinical studies. we wanted to study the prevalence of allergen-specific Immunoglobulin (Ig)E antibodies in two cross-sectional, adult population-based serum samples two decades apart. Since the sera had been tested for H. pylori antibodies, we also had a chance to look for a possible relationship between these two findings. Methods We determined the prevalence rate of allergen-specific serum IgE antibodies against birch and timothy pollen, and cat and dog epithelium allergens by the radioallergosorbent test in a 15-54-years-old Finnish population using 326 sera collected in 1973 and 319 sera collected in 1994 from randomly selected subjects. Results From 1973 to 1994 allergen-specific IgE prevalence rates and IgE antibody levels rose. In 1994, the prevalence rate of positive findings in 15-24-year-old population had increased from I I to 38% (3.5-fold increase, P=0.0001, OR 5.12, Cl 95% 2.32-11.3). In older 10-year age groups similar trends did not reach significance, but the overall change was significant with all three cut-off levels of allergen-specific IgE analysed. The percentage of IgE-positive persons rose mainly in the subgroup with no H. pylori antibodies. In 1994 21% of the H. pylori-negative subjects had IgE antibodies compared with 5% of the H. pylori-positive subjects (in 1973 11% in both subgroups). Conclusions IgE-based evidence for an increase in IgE-mediated allergy was uncovered. The increase occurred mainly in the subgroup with no antibodies to H. pylori, which support the hypothesis that H, pylori could be one of the microbes counteracting atopy.	27	75	2002	6	10.1046/j.1365-2222.2002.01330.x	Allergy; Immunology
"Pediatric allergic rhinitis and comorbid disorders. Allergic rhinitis (AR) is rarely found in isolation and needs to be considered in the context of systemic allergic disease associated with numerous comorbid disorders, including asthma, chronic middle ear effusions, sinusitis, lymphoid hypertrophy with obstructive sleep apnea, disordered sleep, and consequent behavioral and educational effects. The coexistence of AR and asthma is complex. First, the diagnosis of asthma may be confounded by symptoms of cough caused by rhinitis and postnasal drip. This may lead to either inaccurate diagnosis of asthma or inappropriate assessment of asthma severity with over treatment of the patient. The term ""cough variant rhinitis"" is therefore proposed to describe rhinitis that manifests itself primarily as cough that results from postnasal drip. AR, however, also has a causal role in asthma; it appears both to be responsible for exacerbating asthma and to have a role in its pathogenesis. Postnasal drip with nasopharyngeal inflammation leads to a number of other conditions. Thus sinusitis is a frequent extension of rhinitis and is one of the most frequently missed diagnoses In children. Allergen exposure in the nasopharynx with release of histamine and other mediators can cause Eustachian tube obstruction possibly leading to middle car effusions. Chronic allergic inflammation of the upper airway causes lymphoid hypertrophy with prominence of adenoidal and tonsillar tissue. This may be associated with poor appetite, poor growth, and obstructive sleep apnea. AR is therefore part of a spectrum of allergic disorders that can profoundly affect the well being and quality of life of a child. Prospective cohort studies are required to assess the disease burden caused by AR in childhood and to further assess the potential educational impairment that may result. Because AR is part of a systemic disease process, its management requires a coordinated approach rather than a fragmented, organ-based approach.. allergic rhinitis| asthma| cough variant rhinitis| postnasal drip| sinusitis|intercellular-adhesion molecule-1| eustachian-tube obstruction| nasal epithelial-cells| otitis-media| pollen exposure| dose-response| asthma| children| challenge| histamine."	JUL-2001	allergic rhinitis| asthma| cough variant rhinitis| postnasal drip| sinusitis|intercellular-adhesion molecule-1| eustachian-tube obstruction| nasal epithelial-cells| otitis-media| pollen exposure| dose-response| asthma| children| challenge| histamine	Lack, G	Pediatric allergic rhinitis and comorbid disorders		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergic rhinitis; asthma; cough variant rhinitis; postnasal drip; sinusitis	INTERCELLULAR-ADHESION MOLECULE-1; EUSTACHIAN-TUBE OBSTRUCTION; NASAL EPITHELIAL-CELLS; OTITIS-MEDIA; POLLEN EXPOSURE; DOSE-RESPONSE; ASTHMA; CHILDREN; CHALLENGE; HISTAMINE	"Allergic rhinitis (AR) is rarely found in isolation and needs to be considered in the context of systemic allergic disease associated with numerous comorbid disorders, including asthma, chronic middle ear effusions, sinusitis, lymphoid hypertrophy with obstructive sleep apnea, disordered sleep, and consequent behavioral and educational effects. The coexistence of AR and asthma is complex. First, the diagnosis of asthma may be confounded by symptoms of cough caused by rhinitis and postnasal drip. This may lead to either inaccurate diagnosis of asthma or inappropriate assessment of asthma severity with over treatment of the patient. The term ""cough variant rhinitis"" is therefore proposed to describe rhinitis that manifests itself primarily as cough that results from postnasal drip. AR, however, also has a causal role in asthma; it appears both to be responsible for exacerbating asthma and to have a role in its pathogenesis. Postnasal drip with nasopharyngeal inflammation leads to a number of other conditions. Thus sinusitis is a frequent extension of rhinitis and is one of the most frequently missed diagnoses In children. Allergen exposure in the nasopharynx with release of histamine and other mediators can cause Eustachian tube obstruction possibly leading to middle car effusions. Chronic allergic inflammation of the upper airway causes lymphoid hypertrophy with prominence of adenoidal and tonsillar tissue. This may be associated with poor appetite, poor growth, and obstructive sleep apnea. AR is therefore part of a spectrum of allergic disorders that can profoundly affect the well being and quality of life of a child. Prospective cohort studies are required to assess the disease burden caused by AR in childhood and to further assess the potential educational impairment that may result. Because AR is part of a systemic disease process, its management requires a coordinated approach rather than a fragmented, organ-based approach."	39	75	2001	7	10.1067/mai.2001.115562	Allergy; Immunology
Multiple pollen sensitization: A molecular approach to the diagnosis. Background: Sensitization to multiple pollen species is a frequent diagnostic event. Several allergenic molecules with a high level of homology have been identified in divergent pollen families and named panallergens. Methods: We sought to define the criteria to evaluate the prevalence of the multiple pollen sensitization, to identify specific markers of this condition, and to correlate them with the underlying allergic disease. Patients presenting an allergic respiratory disease underwent skin testing with 23 pollens. Patients fulfilling predefined selection criteria were grouped and classified as having multiple pollen sensitization. Patients in each subgroup were tested for IgE to rBet v 2, rJun o 2, rBet v 1, rPhl p 5 and bromelain. Demographical, allergological and clinical data were recorded in the subgroup of patients with multiple pollen sensitization. Results: Seventeen percent of the pollen-sensitized patients formed the multiple pollen-sensitized subgroup. These subjects were positive for most of the pollen species tested regardless of known exposure to them. None of the subjects sensitized to less than six pollen species were positive to panallergens, whereas 55% of the sera of the multiple pollen-sensitized group were positive to rBet v 2, and 15% to rJun o 2. IgE to rBet v 1 and rPhl p 5 were found positive in all the subgroups. Age, gender, bronchial asthma, oral allergy syndrome, skin test reactivity and previous specific immunotherapy differed significantly when these two subsets were considered. Conclusions: Allergy diagnosis based on allergenic molecules is crucial in the patient with multiple pollen sensitization. This condition appears to be determined by the sensitization to defined allergenic components (panallergens) rather than by pollen of multiple species as such. Detection of IgE to nonpanallergenic molecules allows to identify more relevant allergenic sources. Clinical aspects of the underlying allergic disease (e.g. asthma and oral allergy syndrome) seem to be differently related to IgE reactivity to panallergens. Ccpyright (C) 2001 S. Karger AG, Basel. asthma| ige| pollens| recombinant allergens| skin tests|reactive carbohydrate determinants| in-vitro diagnostics| birch pollen| bronchial hyperresponsiveness| allergic diseases| major allergen| ige-binding| tree pollen| identification| immunotherapy.	MAY-2001	asthma| ige| pollens| recombinant allergens| skin tests|reactive carbohydrate determinants| in-vitro diagnostics| birch pollen| bronchial hyperresponsiveness| allergic diseases| major allergen| ige-binding| tree pollen| identification| immunotherapy	Mari, A	Multiple pollen sensitization: A molecular approach to the diagnosis		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	asthma; IgE; pollens; recombinant allergens; skin tests	REACTIVE CARBOHYDRATE DETERMINANTS; IN-VITRO DIAGNOSTICS; BIRCH POLLEN; BRONCHIAL HYPERRESPONSIVENESS; ALLERGIC DISEASES; MAJOR ALLERGEN; IGE-BINDING; TREE POLLEN; IDENTIFICATION; IMMUNOTHERAPY	Background: Sensitization to multiple pollen species is a frequent diagnostic event. Several allergenic molecules with a high level of homology have been identified in divergent pollen families and named panallergens. Methods: We sought to define the criteria to evaluate the prevalence of the multiple pollen sensitization, to identify specific markers of this condition, and to correlate them with the underlying allergic disease. Patients presenting an allergic respiratory disease underwent skin testing with 23 pollens. Patients fulfilling predefined selection criteria were grouped and classified as having multiple pollen sensitization. Patients in each subgroup were tested for IgE to rBet v 2, rJun o 2, rBet v 1, rPhl p 5 and bromelain. Demographical, allergological and clinical data were recorded in the subgroup of patients with multiple pollen sensitization. Results: Seventeen percent of the pollen-sensitized patients formed the multiple pollen-sensitized subgroup. These subjects were positive for most of the pollen species tested regardless of known exposure to them. None of the subjects sensitized to less than six pollen species were positive to panallergens, whereas 55% of the sera of the multiple pollen-sensitized group were positive to rBet v 2, and 15% to rJun o 2. IgE to rBet v 1 and rPhl p 5 were found positive in all the subgroups. Age, gender, bronchial asthma, oral allergy syndrome, skin test reactivity and previous specific immunotherapy differed significantly when these two subsets were considered. Conclusions: Allergy diagnosis based on allergenic molecules is crucial in the patient with multiple pollen sensitization. This condition appears to be determined by the sensitization to defined allergenic components (panallergens) rather than by pollen of multiple species as such. Detection of IgE to nonpanallergenic molecules allows to identify more relevant allergenic sources. Clinical aspects of the underlying allergic disease (e.g. asthma and oral allergy syndrome) seem to be differently related to IgE reactivity to panallergens. Ccpyright (C) 2001 S. Karger AG, Basel	37	75	2001	9	10.1159/000053797	Allergy; Immunology
Effect of ozone and nitrogen dioxide on the release of proinflammatory mediators from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients in vitro. Background: Although studies have suggested that ozone (O-3) and nitrogen dioxide (NO2) may play a role in the pathogenesis of asthma, the underlying mechanisms are not clear. Objective: We aimed to investigate the effects of O-3 and NO2 on the release of IL-8, GM-CSF, RANTES, and soluble intercellular adhesion molecule 1 (sICAM-1) from human bronchial epithelial cells (HBF,Cs) of nonatopic nonasthmatic subjects (nonasthmatic subjects) and atopic subjects with mild asthma (asthmatic subjects) in vitro. Methods: We cultured HBECs from bronchial biopsy specimens of nonasthmatic and asthmatic subjects; exposed these for 6 hours to air, 10 to 100 ppb O-3, or 100 to 400 ppb NO2; and analyzed the release of IL-8, GM-CSF, RANTES, and sICAM-1 after 24 hours' incubation. Results: There was no significant difference between the constitutive release of IL-8, GM-CSF; and sICAM-1 from HBECs of asthmatic and nonasthmatic subjects, RANTES was detected only in HBECs derived from asthmatic subjects. Exposure of HBECs of asthmatic subjects to both 50 to 100 ppb O-3 and 200 to 400 ppb NO2 significantly increased the release of IL-8, GM-CSF, RANTES, and sICAM-1 from these cells after 24 hours of incubation. However, 50 to 100 ppb O-3 and 200 to 400 ppb NO2 led to a significant increase in release of only IL-8 and sICAM-1 from HBECs of nonasthmatic subjects after 24 hours' incubation. A comparison between the pollutant-induced release of mediators demonstrated that 100 ppb O-3. induced release of GM-CSF and sICAM-1 was significantly greater in HBECs of asthmatic subjects (medians, 0.59 and 27.4 pg/mug cellular protein, respectively) than in HBECs of nonasthmatic subjects (medians, 0.27 and 14.4 pg/mug cellular protein, respectively; P<.02). Conclusion: These results suggest that O-3 and NO2 may modulate airway diseases, such as asthma, by increasing the release of inflammatory mediators from bronchial epithelial cells and that the cells of asthmatic subjects may be more susceptible to the adverse effects of these pollutants.. atopic asthma| ozone| nitrogen dioxide| bronchial epithelial cells| cytokines| soluble intercellular adhesion molecule 1|inflammatory mediators| inhaled allergen| air-pollution| in-vitro| responses| cytokines.	FEB-2001	atopic asthma| ozone| nitrogen dioxide| bronchial epithelial cells| cytokines| soluble intercellular adhesion molecule 1|inflammatory mediators| inhaled allergen| air-pollution| in-vitro| responses| cytokines	Bayram, H; Sapsford, RJ; Abdelaziz, MM; Khair, OA	Effect of ozone and nitrogen dioxide on the release of proinflammatory mediators from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients in vitro		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopic asthma; ozone; nitrogen dioxide; bronchial epithelial cells; cytokines; soluble intercellular adhesion molecule 1	INFLAMMATORY MEDIATORS; INHALED ALLERGEN; AIR-POLLUTION; IN-VITRO; RESPONSES; CYTOKINES	Background: Although studies have suggested that ozone (O-3) and nitrogen dioxide (NO2) may play a role in the pathogenesis of asthma, the underlying mechanisms are not clear. Objective: We aimed to investigate the effects of O-3 and NO2 on the release of IL-8, GM-CSF, RANTES, and soluble intercellular adhesion molecule 1 (sICAM-1) from human bronchial epithelial cells (HBF,Cs) of nonatopic nonasthmatic subjects (nonasthmatic subjects) and atopic subjects with mild asthma (asthmatic subjects) in vitro. Methods: We cultured HBECs from bronchial biopsy specimens of nonasthmatic and asthmatic subjects; exposed these for 6 hours to air, 10 to 100 ppb O-3, or 100 to 400 ppb NO2; and analyzed the release of IL-8, GM-CSF, RANTES, and sICAM-1 after 24 hours' incubation. Results: There was no significant difference between the constitutive release of IL-8, GM-CSF; and sICAM-1 from HBECs of asthmatic and nonasthmatic subjects, RANTES was detected only in HBECs derived from asthmatic subjects. Exposure of HBECs of asthmatic subjects to both 50 to 100 ppb O-3 and 200 to 400 ppb NO2 significantly increased the release of IL-8, GM-CSF, RANTES, and sICAM-1 from these cells after 24 hours of incubation. However, 50 to 100 ppb O-3 and 200 to 400 ppb NO2 led to a significant increase in release of only IL-8 and sICAM-1 from HBECs of nonasthmatic subjects after 24 hours' incubation. A comparison between the pollutant-induced release of mediators demonstrated that 100 ppb O-3. induced release of GM-CSF and sICAM-1 was significantly greater in HBECs of asthmatic subjects (medians, 0.59 and 27.4 pg/mug cellular protein, respectively) than in HBECs of nonasthmatic subjects (medians, 0.27 and 14.4 pg/mug cellular protein, respectively; P<.02). Conclusion: These results suggest that O-3 and NO2 may modulate airway diseases, such as asthma, by increasing the release of inflammatory mediators from bronchial epithelial cells and that the cells of asthmatic subjects may be more susceptible to the adverse effects of these pollutants.	28	75	2001	8	10.1067/mai.2001.111141	Allergy; Immunology
"Identification of human lung and skin proteins conjugated with hexamethylene diisocyanate in vitro and in vivo. Diiisocyanates are asthma-causing chemicals used in the commercial production of polyurethane. We have previously shown that human lung epithelial cell proteins can become conjugated with hexamethylene diisocyanate (HDI) and may be biologically important in diisocyanate-induced asthma. The objective of this study was to identify specific human lung and skin proteins that become conjugated with diisocyanate after in vitro and in vivo exposure. Following in vitro exposure of human airway epithelial cells (A549), keratin 18, the 78-kD glucose-regulated protein, trans-1,2-dihyrobenzene-1,2-diol dehydrogenase, and actin were identified as prominent diisocyanate-conjugated proteins through use of a combination of immunocytochemical and mass spectrometric techniques. Following in vivo inhalation of an HDI aerosol, keratin 18 was also identified as the predominant diisocyanate-conjugated protein in human endobronchial biopsy samples, whereas albumin was the predominant diisocyanate-conjugated protein in bronchoalveolar lavage fluid. Keratin was also identified as a predominant diisocyanate-conjugated protein in human skin biopsy samples after epicutaneous exposure to liquid-phase HDI, although the major skin diisocyanate-conjugated protein (56-kD) differed from the predominant lung diisocyanate-conjugated keratin (47-kD). The data from this study identify keratin and other proteins as potential ""carriers"" for diisocyanates in vivo, and suggest that HDI conjugation of these proteins may play a role in the pathogenesis of diisocyanate-induced asthma.. glucose-regulated protein| occupational asthma| guinea-pigs| isocyanate| exposure| adducts| ige| association| expression| antibodies."	DEC-2000	glucose-regulated protein| occupational asthma| guinea-pigs| isocyanate| exposure| adducts| ige| association| expression| antibodies	Wisnewski, AV; Srivastava, R; Herick, C; Xu, L; Lemus, R; Cain, H; Magoski, NM; Karol, MH; Bottomly, K; Redlich, CA	Identification of human lung and skin proteins conjugated with hexamethylene diisocyanate in vitro and in vivo		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		GLUCOSE-REGULATED PROTEIN; OCCUPATIONAL ASTHMA; GUINEA-PIGS; ISOCYANATE; EXPOSURE; ADDUCTS; IGE; ASSOCIATION; EXPRESSION; ANTIBODIES	"Diiisocyanates are asthma-causing chemicals used in the commercial production of polyurethane. We have previously shown that human lung epithelial cell proteins can become conjugated with hexamethylene diisocyanate (HDI) and may be biologically important in diisocyanate-induced asthma. The objective of this study was to identify specific human lung and skin proteins that become conjugated with diisocyanate after in vitro and in vivo exposure. Following in vitro exposure of human airway epithelial cells (A549), keratin 18, the 78-kD glucose-regulated protein, trans-1,2-dihyrobenzene-1,2-diol dehydrogenase, and actin were identified as prominent diisocyanate-conjugated proteins through use of a combination of immunocytochemical and mass spectrometric techniques. Following in vivo inhalation of an HDI aerosol, keratin 18 was also identified as the predominant diisocyanate-conjugated protein in human endobronchial biopsy samples, whereas albumin was the predominant diisocyanate-conjugated protein in bronchoalveolar lavage fluid. Keratin was also identified as a predominant diisocyanate-conjugated protein in human skin biopsy samples after epicutaneous exposure to liquid-phase HDI, although the major skin diisocyanate-conjugated protein (56-kD) differed from the predominant lung diisocyanate-conjugated keratin (47-kD). The data from this study identify keratin and other proteins as potential ""carriers"" for diisocyanates in vivo, and suggest that HDI conjugation of these proteins may play a role in the pathogenesis of diisocyanate-induced asthma."	30	75	2000	7		General & Internal Medicine; Respiratory System
Distribution of particulate matter and tissue remodeling in the human lung. We examined the relationship between intrapulmonary particle distribution of carbonaceous and mineral dusts and remodeling of the airways along anatomically distinct airway paths in the lungs of Hispanic males from the central valley of California. Lung autopsy specimens from the Fresno County Coroner's Office were prepared by intratracheal instillation of 2% glutaraldehyde at 30 cm H2O pressure. Two distinct airway paths into the apico-posterior and apico-anterior portions of the left upper lung lobe were followed. Tissue samples for histologic analysis were generally taken from the intrapulmonary second, fourth, sixth, and ninth airway generations. Parenchymal tissues beyond the 12th airway generation of each airway path were also analyzed. There was little evidence of visible particle accumulation in the larger conducting airways (generations 2-6), except in bronchial-associated lymphoid tissues and within peribronchial connective tissue. In contrast, terminal and respiratory bronchioles arising from each pathway revealed varying degrees of wall thickening and remodeling. Walls with marked thickening contained moderate to heavy amounts of carbonaceous and mineral dusts. Wall thickening was associated with increases in collagen and interstitial inflammatory cells, including dust-laden macrophages. These changes were significantly greater in first-generation respiratory bronchioles compared to second- and third-generation respiratory bronchioles. These findings suggest that accumulation of carbonaceous and mineral dust in the lungs is significantly affected by lung anatomy with the greatest retention in centers of lung acini. Furthermore, there is significant remodeling of this transitional zone in humans exposed to ambient particulate matter.. asthma| california| fibrosis| lung pathology| pm2.5| pm10| particulate matter| pigmentation|san-joaquin valley| small airways| cigarette-smoking| diseases| pneumoconiosis| population| parenchyma| particles| exposure.	NOV-2000	asthma| california| fibrosis| lung pathology| pm2.5| pm10| particulate matter| pigmentation|san-joaquin valley| small airways| cigarette-smoking| diseases| pneumoconiosis| population| parenchyma| particles| exposure	Pinkerton, KE; Green, FHY; Saiki, C; Vallyathan, V; Plopper, CG; Gopal, V; Hung, D; Bahne, EB; Lin, SS; Menache, MG; Schenker, MB	Distribution of particulate matter and tissue remodeling in the human lung		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; California; fibrosis; lung pathology; PM2.5; PM10; particulate matter; pigmentation	SAN-JOAQUIN VALLEY; SMALL AIRWAYS; CIGARETTE-SMOKING; DISEASES; PNEUMOCONIOSIS; POPULATION; PARENCHYMA; PARTICLES; EXPOSURE	We examined the relationship between intrapulmonary particle distribution of carbonaceous and mineral dusts and remodeling of the airways along anatomically distinct airway paths in the lungs of Hispanic males from the central valley of California. Lung autopsy specimens from the Fresno County Coroner's Office were prepared by intratracheal instillation of 2% glutaraldehyde at 30 cm H2O pressure. Two distinct airway paths into the apico-posterior and apico-anterior portions of the left upper lung lobe were followed. Tissue samples for histologic analysis were generally taken from the intrapulmonary second, fourth, sixth, and ninth airway generations. Parenchymal tissues beyond the 12th airway generation of each airway path were also analyzed. There was little evidence of visible particle accumulation in the larger conducting airways (generations 2-6), except in bronchial-associated lymphoid tissues and within peribronchial connective tissue. In contrast, terminal and respiratory bronchioles arising from each pathway revealed varying degrees of wall thickening and remodeling. Walls with marked thickening contained moderate to heavy amounts of carbonaceous and mineral dusts. Wall thickening was associated with increases in collagen and interstitial inflammatory cells, including dust-laden macrophages. These changes were significantly greater in first-generation respiratory bronchioles compared to second- and third-generation respiratory bronchioles. These findings suggest that accumulation of carbonaceous and mineral dust in the lungs is significantly affected by lung anatomy with the greatest retention in centers of lung acini. Furthermore, there is significant remodeling of this transitional zone in humans exposed to ambient particulate matter.	32	75	2000	7	10.1289/ehp.001081063	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Diesel exhaust, carbon black, and silica particles display distinct Th1/Th2 modulating activity. Certain particulate air pollutants may play an important role in the increasing prevalence of respiratory allergy by stimulating T helper 2 cell (Th2)-mediated immune responses to common antigens. The study described here examined different particles, diesel exhaust particles (DEP), carbon black particles (CBP), and silica particles (SIP) for their immunomodulating capacity in both primary and secondary immune responses in female BALB/C mice. The primary response was studied after subcutaneous injection of 1 mg of particle together with 10 mug of reporter antigen TNP-OVA (2,4,6-trinitrophenyl coupled to ovalbumin) into the hind paw. Interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) production was assessed in the popliteal lymph node (PLN) at Day 2 and Day 5 after injection by flow cytometry and ELISA. The number of IL-4-containing CD4(+) T cells increased between Day 2 and Day 5 in DEP- and CBP-exposed mice, in contrast to SIP-treated animals. IL-4 production by cultured PLN cells was also significantly increased for DEP- and CBP-treated animals. The secondary response was studied in different organs after an intranasal challenge with TNP-OVA (50 mug), which was given 4 weeks after the initial subcutaneous injection. Five days after challenge the number of antibody-forming cells (AFCs) was assessed in peribronchial lymph nodes (PBLN), spleen, bone marrow, and PLN, and antibody levels were determined in weekly obtained blood samples. It appeared that all particles acted as adjuvant, but the different particles stimulated distinct types of immune responses to TNP-OVA. DEP-treated animals show high IgG1 and IgE levels in serum and high IgG1 and IgE-forming AFC numbers in PBLN, bone marrow, and spleen. CBP-treated animals show even higher IgG1 and IgE levels and AFC numbers, and in addition display IgG2a production. SIP-injected animals display predominantly IgG2a responses. It is concluded that DEP are able to skew the immune response toward the T helper 2 (Th2) side, whereas SIP stimulate a Th1 response and CBP have a mixed activity, stimulating both Th1 and Th2 responses in this model, (C) 2000 Academic Press.. particulate air pollution| immunotoxicology| th1/th2| popliteal lymph node| diesel exhaust particles| carbon black| silica|systemic ige production| adjuvant activity| air-pollution| antibody-production| fine particles| in-vitro| asthma| mice| prevalence| children.	OCT 15-2000	particulate air pollution| immunotoxicology| th1/th2| popliteal lymph node| diesel exhaust particles| carbon black| silica|systemic ige production| adjuvant activity| air-pollution| antibody-production| fine particles| in-vitro| asthma| mice| prevalence| children	van Zijverden, M; van der Pijl, A; Bol, M; van Pinxteren, FA; de Haar, C; Penninks, AH; van Loveren, H; Pieters, R	Diesel exhaust, carbon black, and silica particles display distinct Th1/Th2 modulating activity		TOXICOLOGY AND APPLIED PHARMACOLOGY	particulate air pollution; immunotoxicology; Th1/Th2; popliteal lymph node; diesel exhaust particles; carbon black; silica	SYSTEMIC IGE PRODUCTION; ADJUVANT ACTIVITY; AIR-POLLUTION; ANTIBODY-PRODUCTION; FINE PARTICLES; IN-VITRO; ASTHMA; MICE; PREVALENCE; CHILDREN	Certain particulate air pollutants may play an important role in the increasing prevalence of respiratory allergy by stimulating T helper 2 cell (Th2)-mediated immune responses to common antigens. The study described here examined different particles, diesel exhaust particles (DEP), carbon black particles (CBP), and silica particles (SIP) for their immunomodulating capacity in both primary and secondary immune responses in female BALB/C mice. The primary response was studied after subcutaneous injection of 1 mg of particle together with 10 mug of reporter antigen TNP-OVA (2,4,6-trinitrophenyl coupled to ovalbumin) into the hind paw. Interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) production was assessed in the popliteal lymph node (PLN) at Day 2 and Day 5 after injection by flow cytometry and ELISA. The number of IL-4-containing CD4(+) T cells increased between Day 2 and Day 5 in DEP- and CBP-exposed mice, in contrast to SIP-treated animals. IL-4 production by cultured PLN cells was also significantly increased for DEP- and CBP-treated animals. The secondary response was studied in different organs after an intranasal challenge with TNP-OVA (50 mug), which was given 4 weeks after the initial subcutaneous injection. Five days after challenge the number of antibody-forming cells (AFCs) was assessed in peribronchial lymph nodes (PBLN), spleen, bone marrow, and PLN, and antibody levels were determined in weekly obtained blood samples. It appeared that all particles acted as adjuvant, but the different particles stimulated distinct types of immune responses to TNP-OVA. DEP-treated animals show high IgG1 and IgE levels in serum and high IgG1 and IgE-forming AFC numbers in PBLN, bone marrow, and spleen. CBP-treated animals show even higher IgG1 and IgE levels and AFC numbers, and in addition display IgG2a production. SIP-injected animals display predominantly IgG2a responses. It is concluded that DEP are able to skew the immune response toward the T helper 2 (Th2) side, whereas SIP stimulate a Th1 response and CBP have a mixed activity, stimulating both Th1 and Th2 responses in this model, (C) 2000 Academic Press.	46	75	2000	9	10.1006/taap.2000.9013	Pharmacology & Pharmacy; Toxicology
The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease. Airway hyperresponsiveness (AHR), the exaggerated response to constrictor agonists in asthmatic subjects, is incompletely understood. Changes in either the quantity or properties of airway smooth muscle (ASM) are possible explanations for AHR. Morphometric analyses demonstrate structural changes in asthmatic airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy, neovascularization and an increase in ASM mass. Mathematical modelling of airway narrowing suggests that, of all the changes in structure, the increase in ASM mass is the most probable cause of AHR. An increase in ASM mass in the large airways is more closely associated with a greater likelihood of dying from asthma than increases in ASM mass in other locations within the airway tree. ASM contraction is opposed by the elastic recoil of the lungs and airways, which appears to limit the degree of bronchoconstriction in vivo. The cyclical nature of tidal breathing applies stresses to the airway wall that enhance the bronchodilating influence of the lung tissues on the contracting ASR;I, in all probability by disrupting cross-bridges. However, the increase in ASM mass in asthma may overcome the limitation resulting from the impedances to ASM shortening imposed by the lung parenchyma and airway wall tissues. Additionally, ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a greater degree of bronchoconstriction when stimulated to contract than slower ASM. Changes in ASM properties are induced by the process of sensitization and allergen-exposure such as enhancement of phospholipase C activity and inositol phosphate turnover, and increases in myosin Light chain kinase activity, Whether changes in ASM mass or biochemical/biomechanical properties form the basis for asthma remains to be determined.. airways responsiveness| airway smooth muscle| asthma| mechanics| modelling|brown-norway rats| antigen challenge| guinea-pigs| asthma| bronchoconstriction| mechanics| model| orientation| pressure| exposure.	AUG-2000	airways responsiveness| airway smooth muscle| asthma| mechanics| modelling|brown-norway rats| antigen challenge| guinea-pigs| asthma| bronchoconstriction| mechanics| model| orientation| pressure| exposure	Martin, JG; Duguet, A; Eidelman, DH	The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease		EUROPEAN RESPIRATORY JOURNAL	airways responsiveness; airway smooth muscle; asthma; mechanics; modelling	BROWN-NORWAY RATS; ANTIGEN CHALLENGE; GUINEA-PIGS; ASTHMA; BRONCHOCONSTRICTION; MECHANICS; MODEL; ORIENTATION; PRESSURE; EXPOSURE	Airway hyperresponsiveness (AHR), the exaggerated response to constrictor agonists in asthmatic subjects, is incompletely understood. Changes in either the quantity or properties of airway smooth muscle (ASM) are possible explanations for AHR. Morphometric analyses demonstrate structural changes in asthmatic airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy, neovascularization and an increase in ASM mass. Mathematical modelling of airway narrowing suggests that, of all the changes in structure, the increase in ASM mass is the most probable cause of AHR. An increase in ASM mass in the large airways is more closely associated with a greater likelihood of dying from asthma than increases in ASM mass in other locations within the airway tree. ASM contraction is opposed by the elastic recoil of the lungs and airways, which appears to limit the degree of bronchoconstriction in vivo. The cyclical nature of tidal breathing applies stresses to the airway wall that enhance the bronchodilating influence of the lung tissues on the contracting ASR;I, in all probability by disrupting cross-bridges. However, the increase in ASM mass in asthma may overcome the limitation resulting from the impedances to ASM shortening imposed by the lung parenchyma and airway wall tissues. Additionally, ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a greater degree of bronchoconstriction when stimulated to contract than slower ASM. Changes in ASM properties are induced by the process of sensitization and allergen-exposure such as enhancement of phospholipase C activity and inositol phosphate turnover, and increases in myosin Light chain kinase activity, Whether changes in ASM mass or biochemical/biomechanical properties form the basis for asthma remains to be determined.	44	75	2000	6	10.1034/j.1399-3003.2000.16b25.x	Respiratory System
Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis. Objective--To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. Design--A multicentre randomised double blind placebo controlled trial. Subjects--Infants admitted to hospital with their first episode of RSV positive bronchiolitis. Intervention-Randomised to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. Main outcome measures--Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of antiwheeze medication during follow up. Results--161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure, Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Ma, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (Cl)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants recieving at least one prescription for antiwheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6);bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). Conclusions--There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.. acute viral bronchiolitis| respiratory syncytial virus| inhaled corticosteroids|virus bronchiolitis| lung-function| budesonide| children| infants| asthma| dexamethasone| infection| age.	FEB-2000	acute viral bronchiolitis| respiratory syncytial virus| inhaled corticosteroids|virus bronchiolitis| lung-function| budesonide| children| infants| asthma| dexamethasone| infection| age	Cade, A; Brownlee, KG; Conway, SP; Haigh, D; Short, A; Brown, J; Dassu, D; Mason, SA; Phillips, A; Eglin, R; Graham, M; Chetcuti, A; Chatrath, M; Hudson, N; Thomas, A; Chetcuti, PAJ	Randomised placebo controlled trial of nebulised corticosteroids in acute respiratory syncytial viral bronchiolitis		ARCHIVES OF DISEASE IN CHILDHOOD	acute viral bronchiolitis; respiratory syncytial virus; inhaled corticosteroids	VIRUS BRONCHIOLITIS; LUNG-FUNCTION; BUDESONIDE; CHILDREN; INFANTS; ASTHMA; DEXAMETHASONE; INFECTION; AGE	Objective--To evaluate short and long term effects of giving nebulised budesonide early in respiratory syncytial viral (RSV) bronchiolitis. Design--A multicentre randomised double blind placebo controlled trial. Subjects--Infants admitted to hospital with their first episode of RSV positive bronchiolitis. Intervention-Randomised to receive either 1 mg of nebulised budesonide (Bud) or placebo (Pla) twice daily from admission until 2 weeks after discharge. Follow up was for 12 months. Main outcome measures--Duration of hospital admission, time taken to become symptom free, re-admission rates, general practitioner consultation rates, and use of antiwheeze medication during follow up. Results--161 infants were studied. Both arms were similar with respect to initial clinical severity, age, sex, socioeconomic class, and tobacco exposure, Median time from first nebulisation to discharge: Bud and Pla, 2 days. Median number of days for 50% of infants to be symptom free for 48 hours: Bud, 10 days; Ma, 12 days. Respiratory re-admission rates in the 12 month follow up: Bud, 16%; Pla, 18%; median difference (95% confidence interval (Cl)), -2 (-14 to 10). Median respiratory related general practitioner attendances: Bud, 4.0; Pla, 4.5; median difference (95% CI), -1 (-2 to 0). Percentage of infants recieving at least one prescription for antiwheeze medication during follow up, corticosteroids: Bud, 50%; Pla, 60%; difference (95% CI), -10 (-26 to 6);bronchodilators: Bud, 60%; Pla, 67%; difference (95% CI), -7 (-22 to 8). Conclusions--There are no short or long term clinical benefits from the administration of nebulised corticosteroids in the acute phase of RSV bronchiolitis.	28	75	2000	5	10.1136/adc.82.2.126	Pediatrics
The Effects of Airway Microbiome on Corticosteroid Responsiveness in Asthma. Rationale: The role of airway microbiome in corticosteroid response in asthma is unknown. Objectives: To examine airway microbiome composition in patients with corticosteroid-resistant (CR) asthma and compare it with patients with corticosteroid-sensitive (CS) asthma and normal control subjects and explore whether bacteria in the airways of subjects with asthma may direct alterations in cellular responses to corticosteroids. Methods: 16S rRNA gene sequencing was performed on bronchoalveolar lavage(BAL) samples of 39 subjects with asthma and 12 healthy control subjects. In subjects with asthma, corticosteroid responsiveness was characterized, BAL macrophages were stimulated with pathogenic versus commensal microorganisms, and analyzed by real-time polymerase chain reaction for the expression of corticosteroid-regulated genes and cellular p38 mitogen-activated protein kinase (MAPK) activation. Measurements and Main Results: Of the 39 subjects with asthma, 29 were CR and 10 were CS. BAL microbiome from subjects with CR and CS asthma did not differ in richness, evenness, diversity, and community composition at the phylum level, but did differ at the genus level, with distinct genus expansions in 14 subjects with CR asthma. Preincubation of asthmatic airway macrophages with Haemophilus parainfluenzae, a uniquely expanded potential pathogen found only in CR asthma airways, resulted in p38 MAPK activation, increased IL-8 (P < 0.01), mitogen-activated kinase phosphatase 1 mRNA (P < 0.01) expression, and inhibition of corticosteroid responses (P < 0.05). This was not observed after exposure to commensal bacterium Prevotella melaninogenica. Inhibition of transforming growth factor-beta-associated kinase-1 (TAK1), upstream activator of MAPK, but not p38 MAPK restored cellular sensitivity to corticosteroids. [GRAPHICS] Conclusions: A subset of subjects with CR asthma demonstrates airway expansion of specific gram-negative bacteria, which trigger TAK1/MAPK activation and induce corticosteroid resistance. TAK1 inhibition restored cellular sensitivity to corticosteroids.. microbiome| asthma| corticosteroids|steroid-resistant asthma| glucocorticoid-insensitive asthma| protein-kinase phosphatase-1| fiberoptic bronchoscopy| commensal bacteria| receptor-beta| lipid-a| disease| lipopolysaccharides| macrophages.	NOV 15-2013	microbiome| asthma| corticosteroids|steroid-resistant asthma| glucocorticoid-insensitive asthma| protein-kinase phosphatase-1| fiberoptic bronchoscopy| commensal bacteria| receptor-beta| lipid-a| disease| lipopolysaccharides| macrophages	Goleva, E; Jackson, LP; Harris, JK; Robertson, CE; Sutherland, ER; Hall, CF; Good, JT; Gelfand, EW; Martin, RJ; Leung, DYM	The Effects of Airway Microbiome on Corticosteroid Responsiveness in Asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	microbiome; asthma; corticosteroids	STEROID-RESISTANT ASTHMA; GLUCOCORTICOID-INSENSITIVE ASTHMA; PROTEIN-KINASE PHOSPHATASE-1; FIBEROPTIC BRONCHOSCOPY; COMMENSAL BACTERIA; RECEPTOR-BETA; LIPID-A; DISEASE; LIPOPOLYSACCHARIDES; MACROPHAGES	Rationale: The role of airway microbiome in corticosteroid response in asthma is unknown. Objectives: To examine airway microbiome composition in patients with corticosteroid-resistant (CR) asthma and compare it with patients with corticosteroid-sensitive (CS) asthma and normal control subjects and explore whether bacteria in the airways of subjects with asthma may direct alterations in cellular responses to corticosteroids. Methods: 16S rRNA gene sequencing was performed on bronchoalveolar lavage(BAL) samples of 39 subjects with asthma and 12 healthy control subjects. In subjects with asthma, corticosteroid responsiveness was characterized, BAL macrophages were stimulated with pathogenic versus commensal microorganisms, and analyzed by real-time polymerase chain reaction for the expression of corticosteroid-regulated genes and cellular p38 mitogen-activated protein kinase (MAPK) activation. Measurements and Main Results: Of the 39 subjects with asthma, 29 were CR and 10 were CS. BAL microbiome from subjects with CR and CS asthma did not differ in richness, evenness, diversity, and community composition at the phylum level, but did differ at the genus level, with distinct genus expansions in 14 subjects with CR asthma. Preincubation of asthmatic airway macrophages with Haemophilus parainfluenzae, a uniquely expanded potential pathogen found only in CR asthma airways, resulted in p38 MAPK activation, increased IL-8 (P < 0.01), mitogen-activated kinase phosphatase 1 mRNA (P < 0.01) expression, and inhibition of corticosteroid responses (P < 0.05). This was not observed after exposure to commensal bacterium Prevotella melaninogenica. Inhibition of transforming growth factor-beta-associated kinase-1 (TAK1), upstream activator of MAPK, but not p38 MAPK restored cellular sensitivity to corticosteroids. [GRAPHICS] Conclusions: A subset of subjects with CR asthma demonstrates airway expansion of specific gram-negative bacteria, which trigger TAK1/MAPK activation and induce corticosteroid resistance. TAK1 inhibition restored cellular sensitivity to corticosteroids.	54	74	2013	9	10.1164/rccm.201304-0775OC	General & Internal Medicine; Respiratory System
Changes to Airborne Pollen Counts across Europe. A progressive global increase in the burden of allergic diseases has affected the industrialized world over the last half century and has been reported in the literature. The clinical evidence reveals a general increase in both incidence and prevalence of respiratory diseases, such as allergic rhinitis (common hay fever) and asthma. Such phenomena may be related not only to air pollution and changes in lifestyle, but also to an actual increase in airborne quantities of allergenic pollen. Experimental enhancements of carbon dioxide (CO2) have demonstrated changes in pollen amount and allergenicity, but this has rarely been shown in the wider environment. The present analysis of a continental-scale pollen data set reveals an increasing trend in the yearly amount of airborne pollen for many taxa in Europe, which is more pronounced in urban than semi-rural/rural areas. Climate change may contribute to these changes, however increased temperatures do not appear to be a major influencing factor. Instead, we suggest the anthropogenic rise of atmospheric CO2 levels may be influential.. ambrosia-artemisiifolia l.| climate-change| public-health| allergenic pollen| atmospheric co2| common ragweed| aeroallergens| urbanization| impacts| seasons.	APR 13-2012	ambrosia-artemisiifolia l.| climate-change| public-health| allergenic pollen| atmospheric co2| common ragweed| aeroallergens| urbanization| impacts| seasons	Ziello, C; Sparks, TH; Estrella, N; Belmonte, J; Bergmann, KC; Bucher, E; Brighetti, MA; Damialis, A; Detandt, M; Galan, C; Gehrig, R; Grewling, L; Bustillo, AMG; Hallsdottir, M; Kockhans-Bieda, MC; De Linares, C; Myszkowska, D; Paldy, A; Sanchez, A; Smith, M; Thibaudon, M; Travaglini, A; Uruska, A; Valencia-Barrera, RM; Vokou, D; Wachter, R; de Weger, LA; Menzel, A	Changes to Airborne Pollen Counts across Europe		PLOS ONE		AMBROSIA-ARTEMISIIFOLIA L.; CLIMATE-CHANGE; PUBLIC-HEALTH; ALLERGENIC POLLEN; ATMOSPHERIC CO2; COMMON RAGWEED; AEROALLERGENS; URBANIZATION; IMPACTS; SEASONS	A progressive global increase in the burden of allergic diseases has affected the industrialized world over the last half century and has been reported in the literature. The clinical evidence reveals a general increase in both incidence and prevalence of respiratory diseases, such as allergic rhinitis (common hay fever) and asthma. Such phenomena may be related not only to air pollution and changes in lifestyle, but also to an actual increase in airborne quantities of allergenic pollen. Experimental enhancements of carbon dioxide (CO2) have demonstrated changes in pollen amount and allergenicity, but this has rarely been shown in the wider environment. The present analysis of a continental-scale pollen data set reveals an increasing trend in the yearly amount of airborne pollen for many taxa in Europe, which is more pronounced in urban than semi-rural/rural areas. Climate change may contribute to these changes, however increased temperatures do not appear to be a major influencing factor. Instead, we suggest the anthropogenic rise of atmospheric CO2 levels may be influential.	34	74	2012	8	10.1371/journal.pone.0034076	Science & Technology - Other Topics
Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year. Background: Regulatory T cells (Tregs) with stable FOXP3 expression are characterized by a specific demethylated region in the FOXP3 gene (Treg-specific demethylated region, TSDR). The aim of this study was to analyse the influence of prenatal factors on cord blood Treg numbers, as detected by changes in the TSDR demethylation, and the subsequent risk for allergic diseases. Methods: Analyses were performed within the LINA study in blood samples from pregnant women (34th gestational week) and in cord blood (n = 346 mother-child pairs). Treg numbers were detected via DNA demethylation in the FOXP3 TSDR. At age 1, total and specific IgE was measured in children's blood. In addition, maternal cytokine production (Th1/ Th2/ Th17) was analysed. Exposure and disease outcomes were assessed by questionnaires. Results: Boys had lower Treg numbers compared with girls (P < 0.001). Parental atopy history, particularly maternal hay fever and paternal asthma were related to lower Treg numbers in cord blood (adj. MR = 0.81, 95% CI = 0.68-0.97; adj. MR = 0.60, 95% CI = 0.45-0.81). Maternal cytokines (IL-13, IL-17E and IFN-gamma) and maternal smoking/ exposure to tobacco smoke during pregnancy were also associated with decreased cord blood Treg numbers (adj. MR = 0.89, 95% CI = 0.97-1.00). Children with lower Treg numbers at birth had a higher risk to develop atopic dermatitis (adj. OR = 1.55, 95% CI = 1.00-2.41) and sensitization to food allergens (adj. OR = 1.55, 95% CI = 1.06-2.25) during the first year of life. Conclusions: These results indicate that both genetic and environmental factors presumably influence the development of foetal Tregs. Low cord blood Treg numbers may predict early atopic dermatitis.. birth cohort| cord blood| environmental exposure| foxp3| regulatory t cells|regulatory t-cells| immune-responses| peripheral-blood| maternal smoking| dna methylation| lineage| induction| pregnancy| children| disease.	MAR-2012	birth cohort| cord blood| environmental exposure| foxp3| regulatory t cells|regulatory t-cells| immune-responses| peripheral-blood| maternal smoking| dna methylation| lineage| induction| pregnancy| children| disease	Hinz, D; Bauer, M; Roder, S; Olek, S; Huehn, J; Sack, U; Borte, M; Simon, JC; Lehmann, I; Herberth, G	Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year		ALLERGY	birth cohort; cord blood; environmental exposure; FOXP3; regulatory T cells	REGULATORY T-CELLS; IMMUNE-RESPONSES; PERIPHERAL-BLOOD; MATERNAL SMOKING; DNA METHYLATION; LINEAGE; INDUCTION; PREGNANCY; CHILDREN; DISEASE	Background: Regulatory T cells (Tregs) with stable FOXP3 expression are characterized by a specific demethylated region in the FOXP3 gene (Treg-specific demethylated region, TSDR). The aim of this study was to analyse the influence of prenatal factors on cord blood Treg numbers, as detected by changes in the TSDR demethylation, and the subsequent risk for allergic diseases. Methods: Analyses were performed within the LINA study in blood samples from pregnant women (34th gestational week) and in cord blood (n = 346 mother-child pairs). Treg numbers were detected via DNA demethylation in the FOXP3 TSDR. At age 1, total and specific IgE was measured in children's blood. In addition, maternal cytokine production (Th1/ Th2/ Th17) was analysed. Exposure and disease outcomes were assessed by questionnaires. Results: Boys had lower Treg numbers compared with girls (P < 0.001). Parental atopy history, particularly maternal hay fever and paternal asthma were related to lower Treg numbers in cord blood (adj. MR = 0.81, 95% CI = 0.68-0.97; adj. MR = 0.60, 95% CI = 0.45-0.81). Maternal cytokines (IL-13, IL-17E and IFN-gamma) and maternal smoking/ exposure to tobacco smoke during pregnancy were also associated with decreased cord blood Treg numbers (adj. MR = 0.89, 95% CI = 0.97-1.00). Children with lower Treg numbers at birth had a higher risk to develop atopic dermatitis (adj. OR = 1.55, 95% CI = 1.00-2.41) and sensitization to food allergens (adj. OR = 1.55, 95% CI = 1.06-2.25) during the first year of life. Conclusions: These results indicate that both genetic and environmental factors presumably influence the development of foetal Tregs. Low cord blood Treg numbers may predict early atopic dermatitis.	33	74	2012	10	10.1111/j.1398-9995.2011.02767.x	Allergy; Immunology
"Oxidative Stress-induced Antibodies to Carbonyl-modified Protein Correlate with Severity of Chronic Obstructive Pulmonary Disease. Rationale: There is increasing evidence for the presence of autoantibodies in chronic obstructive pulmonary disease (COPD). Chronic oxidative stress is an essential component in COPD pathogenesis and can lead to increased levels of highly reactive carbonyls in the lung, which could result in the formation of highly immunogenic carbonyl adducts on ""self"" proteins. Objectives: To determine the presence of autoantibodies to carbonyl-modified protein in patients with COPD and in a murine model of chronic ozone exposure. To assess the extent of activated immune responses toward carbonyl-modified proteins. Methods: Blood and peripheral lung were taken from patients with COPD, age-matched smokers, and nonsmokers with normal lung function, as well as patients with severe persistent asthma. Mice were exposed to ambient air or ozone for 6 weeks. Antibody titers were measured by ELISA, activated compliment deposition by immunohistochemistry, and cellular activation by ELISA and fluorescence-activated cell sorter. Measurements and Main Results: Antibody titer against carbonyl-modified self-protein was significantly increased in patients with Global Initiative for Chronic Obstructive Lung Disease stage III COPD compared with control subjects. Antibody levels inversely correlated with disease severity and showed a prevalence toward an IgG1 isotype. Deposition of activated complement in the vessels of COPD lung as well as autoantibodies against endothelial cells were also observed. Ozone-exposed mice similarly exhibited increased antibody titers to carbonyl-modified protein, as well as activated antigen-presenting cells in lung tissue and splenocytes sensitized to activation by carbonyl-modified protein. Conclusions: Carbonyl-modified proteins, arising as a result of oxidative stress, promote antibody production, providing a link by which oxidative stress could drive an autoimmune response in COPD.. copd| autoimmunity| oxidative stress| carbonyl|lipid-peroxidation products| cigarette-smoke| induced emphysema| t-cells| copd| autoantibodies| autoimmunity| mice| autoantigens| inflammation."	OCT 1-2011	copd| autoimmunity| oxidative stress| carbonyl|lipid-peroxidation products| cigarette-smoke| induced emphysema| t-cells| copd| autoantibodies| autoimmunity| mice| autoantigens| inflammation	Kirkham, PA; Caramori, G; Casolari, P; Papi, AA; Edwards, M; Shamji, B; Triantaphyllopoulos, K; Hussain, F; Pinart, M; Khan, Y; Heinemann, L; Stevens, L; Yeadon, M; Barnes, PJ; Chung, KF; Adcock, IM	Oxidative Stress-induced Antibodies to Carbonyl-modified Protein Correlate with Severity of Chronic Obstructive Pulmonary Disease		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	COPD; autoimmunity; oxidative stress; carbonyl	LIPID-PEROXIDATION PRODUCTS; CIGARETTE-SMOKE; INDUCED EMPHYSEMA; T-CELLS; COPD; AUTOANTIBODIES; AUTOIMMUNITY; MICE; AUTOANTIGENS; INFLAMMATION	"Rationale: There is increasing evidence for the presence of autoantibodies in chronic obstructive pulmonary disease (COPD). Chronic oxidative stress is an essential component in COPD pathogenesis and can lead to increased levels of highly reactive carbonyls in the lung, which could result in the formation of highly immunogenic carbonyl adducts on ""self"" proteins. Objectives: To determine the presence of autoantibodies to carbonyl-modified protein in patients with COPD and in a murine model of chronic ozone exposure. To assess the extent of activated immune responses toward carbonyl-modified proteins. Methods: Blood and peripheral lung were taken from patients with COPD, age-matched smokers, and nonsmokers with normal lung function, as well as patients with severe persistent asthma. Mice were exposed to ambient air or ozone for 6 weeks. Antibody titers were measured by ELISA, activated compliment deposition by immunohistochemistry, and cellular activation by ELISA and fluorescence-activated cell sorter. Measurements and Main Results: Antibody titer against carbonyl-modified self-protein was significantly increased in patients with Global Initiative for Chronic Obstructive Lung Disease stage III COPD compared with control subjects. Antibody levels inversely correlated with disease severity and showed a prevalence toward an IgG1 isotype. Deposition of activated complement in the vessels of COPD lung as well as autoantibodies against endothelial cells were also observed. Ozone-exposed mice similarly exhibited increased antibody titers to carbonyl-modified protein, as well as activated antigen-presenting cells in lung tissue and splenocytes sensitized to activation by carbonyl-modified protein. Conclusions: Carbonyl-modified proteins, arising as a result of oxidative stress, promote antibody production, providing a link by which oxidative stress could drive an autoimmune response in COPD."	43	74	2011	7	10.1164/rccm.201010-1605OC	General & Internal Medicine; Respiratory System
Peat Bog Wildfire Smoke Exposure in Rural North Carolina Is Associated with Cardiopulmonary Emergency Department Visits Assessed through Syndromic Surveillance. BACKGROUND: In June 2008, burning peat deposits produced haze and air pollution far in excess of National Ambient Air Quality Standards, encroaching on rural communities of eastern North Carolina. Although the association of mortality and morbidity with exposure to urban air pollution is well established, the health effects associated with exposure to wildfire emissions are less well understood. OBJECTIVE: We investigated the effects of exposure on cardiorespiratory outcomes in the population affected by the fire. METHODS: We performed a population-based study using emergency department (ED) visits reported through the syndromic surveillance program NC DETECT (North Carolina Disease Event Tracking and Epidemiologic Collection Tool). We used aerosol optical depth measured by a satellite to determine a high-exposure window and distinguish counties most impacted by the dense smoke plume from surrounding referent counties. Poisson log-linear regression with a 5-day distributed lag was used to estimate changes in the cumulative relative risk (RR). RESULTS: In the exposed counties, significant increases in cumulative RR for asthma [1.65 (95% confidence interval, 1.25-2.1)], chronic obstructive pulmonary disease [1.73 (1.06-2.83)], and pneumonia and acute bronchitis [1.59 (1.07-2.34)] were observed. ED visits associated with cardiopulmonary symptoms [1.23 (1.06-1.43)] and heart failure [1.37 (1.01-1.85)] were also significantly increased. CONCLUSIONS: Satellite data and syndromic surveillance were combined to assess the health impacts of wildfire smoke in rural counties with sparse air-quality monitoring. This is the first study to demonstrate both respiratory and cardiac effects after brief exposure to peat wildfire smoke.. cardiopulmonary health effects| satellite data| syndromic surveillance| wildfire smoke exposure|particulate air-pollution| southern california wildfires| congestive-heart-failure| forest-fires| hospital admissions| united-states| room visits| urban area| quality| mortality.	OCT-2011	cardiopulmonary health effects| satellite data| syndromic surveillance| wildfire smoke exposure|particulate air-pollution| southern california wildfires| congestive-heart-failure| forest-fires| hospital admissions| united-states| room visits| urban area| quality| mortality	Rappold, AG; Stone, SL; Cascio, WE; Neas, LM; Kilaru, VJ; Carraway, MS; Szykman, JJ; Ising, A; Cleve, WE; Meredith, JT; Vaughan-Batten, H; Deyneka, L; Devlin, RB	Peat Bog Wildfire Smoke Exposure in Rural North Carolina Is Associated with Cardiopulmonary Emergency Department Visits Assessed through Syndromic Surveillance		ENVIRONMENTAL HEALTH PERSPECTIVES	cardiopulmonary health effects; satellite data; syndromic surveillance; wildfire smoke exposure	PARTICULATE AIR-POLLUTION; SOUTHERN CALIFORNIA WILDFIRES; CONGESTIVE-HEART-FAILURE; FOREST-FIRES; HOSPITAL ADMISSIONS; UNITED-STATES; ROOM VISITS; URBAN AREA; QUALITY; MORTALITY	BACKGROUND: In June 2008, burning peat deposits produced haze and air pollution far in excess of National Ambient Air Quality Standards, encroaching on rural communities of eastern North Carolina. Although the association of mortality and morbidity with exposure to urban air pollution is well established, the health effects associated with exposure to wildfire emissions are less well understood. OBJECTIVE: We investigated the effects of exposure on cardiorespiratory outcomes in the population affected by the fire. METHODS: We performed a population-based study using emergency department (ED) visits reported through the syndromic surveillance program NC DETECT (North Carolina Disease Event Tracking and Epidemiologic Collection Tool). We used aerosol optical depth measured by a satellite to determine a high-exposure window and distinguish counties most impacted by the dense smoke plume from surrounding referent counties. Poisson log-linear regression with a 5-day distributed lag was used to estimate changes in the cumulative relative risk (RR). RESULTS: In the exposed counties, significant increases in cumulative RR for asthma [1.65 (95% confidence interval, 1.25-2.1)], chronic obstructive pulmonary disease [1.73 (1.06-2.83)], and pneumonia and acute bronchitis [1.59 (1.07-2.34)] were observed. ED visits associated with cardiopulmonary symptoms [1.23 (1.06-1.43)] and heart failure [1.37 (1.01-1.85)] were also significantly increased. CONCLUSIONS: Satellite data and syndromic surveillance were combined to assess the health impacts of wildfire smoke in rural counties with sparse air-quality monitoring. This is the first study to demonstrate both respiratory and cardiac effects after brief exposure to peat wildfire smoke.	39	74	2011	6	10.1289/ehp.1003206	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Inhaled corticosteroids as combination therapy with beta-adrenergic agonists in airways disease: present and future. Inhaled corticosteroid (ICS) therapy in combination with long-acting beta-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting beta-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 mu g daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 mu g daily, and addition of the LABA formoterol to budesonide (800 mu g) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV(1) and the rate of exacerbations. A reduction in the rate of decline in FEV(1) of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases.. asthma| chronic obstructive pulmonary disease| corticosteroids| beta-adrenergic agonists| inflammation|obstructive pulmonary-disease| randomized controlled-trial| histone deacetylase activity| mild persistent asthma| bone-mineral density| long-term treatment| air-flow obstruction| nitric-oxide levels| low-dose budesonide| regulatory t-cells.	SEP-2009	asthma| chronic obstructive pulmonary disease| corticosteroids| beta-adrenergic agonists| inflammation|obstructive pulmonary-disease| randomized controlled-trial| histone deacetylase activity| mild persistent asthma| bone-mineral density| long-term treatment| air-flow obstruction| nitric-oxide levels| low-dose budesonide| regulatory t-cells	Chung, KF; Caramori, G; Adcock, IM	Inhaled corticosteroids as combination therapy with beta-adrenergic agonists in airways disease: present and future		EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY	Asthma; Chronic obstructive pulmonary disease; Corticosteroids; Beta-adrenergic agonists; Inflammation	OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; HISTONE DEACETYLASE ACTIVITY; MILD PERSISTENT ASTHMA; BONE-MINERAL DENSITY; LONG-TERM TREATMENT; AIR-FLOW OBSTRUCTION; NITRIC-OXIDE LEVELS; LOW-DOSE BUDESONIDE; REGULATORY T-CELLS	Inhaled corticosteroid (ICS) therapy in combination with long-acting beta-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting beta-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 mu g daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 mu g daily, and addition of the LABA formoterol to budesonide (800 mu g) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV(1) and the rate of exacerbations. A reduction in the rate of decline in FEV(1) of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases.	215	74	2009	19	10.1007/s00228-009-0682-z	Pharmacology & Pharmacy
Alternatively Activated Macrophages Elicited by Helminth Infection Can Be Reprogrammed to Enable Microbial Killing. The prime function of classically activated macrophages (activated by Th1-type signals, such as IFN-gamma) is microbial destruction. Alternatively activated macrophages (activated by Th2 cytokines, such as IL-4 and IL-13) play important roles in allergy and responses to helminth infection. We utilize a murine model of filarial infection, in which adult nematodes are surgically implanted into the peritoneal cavity of mice, as an in vivo source of alternatively activated macrophages. At 3 wk postinfection, the peritoneal exudate cell population is dominated by macrophages, termed nematode-elicited macrophages (NeM phi), that display IL-4-dependent features such as the expression of arginase 1, RELM-alpha (resistin-like molecule alpha), and Ym1. Since increasing evidence suggests that macrophages show functional adaptivity, the response of NeM phi to proinflammatory Th1-activating signals was investigated to determine whether a switch between alternative and classical activation could occur in macrophages differentiated in an in vivo infection setting. Despite the long-term exposure to Th2 cytokines and antiinflammatory signals in vivo, we found that NeM phi were not terminally differentiated but could develop a more classically activated phenotype in response to LPS and IFN-gamma. This was reflected by a switch in the enzymatic pathway for arginine metabolism from arginase to inducible NO synthase and the reduced expression of RELM-alpha and Ym1. Furthermore, this enabled NeM phi to become antimicrobial, as LPS/IFN-gamma-treated NeM phi produced NO that mediated killing of Leishmania mexicana. However, the adaptation to antimicrobial function did not extend to key regulatory pathways, such as IL-12 production, which remained unaltered. The Journal of Immunology, 2009, 182: 3084-3094.. antigen-presenting cells| cd4(+) t-cells| tumor-infiltrating macrophages| leishmania-mexicana infection| oxide-synthesizing pathway| synthase arginase balance| selective up-regulation| in-vivo| peritoneal-macrophages| murine macrophages.	MAR 1-2009	antigen-presenting cells| cd4(+) t-cells| tumor-infiltrating macrophages| leishmania-mexicana infection| oxide-synthesizing pathway| synthase arginase balance| selective up-regulation| in-vivo| peritoneal-macrophages| murine macrophages	Mylonas, KJ; Nair, MG; Prieto-Lafuente, L; Paape, D; Allen, JE	Alternatively Activated Macrophages Elicited by Helminth Infection Can Be Reprogrammed to Enable Microbial Killing		JOURNAL OF IMMUNOLOGY		ANTIGEN-PRESENTING CELLS; CD4(+) T-CELLS; TUMOR-INFILTRATING MACROPHAGES; LEISHMANIA-MEXICANA INFECTION; OXIDE-SYNTHESIZING PATHWAY; SYNTHASE ARGINASE BALANCE; SELECTIVE UP-REGULATION; IN-VIVO; PERITONEAL-MACROPHAGES; MURINE MACROPHAGES	The prime function of classically activated macrophages (activated by Th1-type signals, such as IFN-gamma) is microbial destruction. Alternatively activated macrophages (activated by Th2 cytokines, such as IL-4 and IL-13) play important roles in allergy and responses to helminth infection. We utilize a murine model of filarial infection, in which adult nematodes are surgically implanted into the peritoneal cavity of mice, as an in vivo source of alternatively activated macrophages. At 3 wk postinfection, the peritoneal exudate cell population is dominated by macrophages, termed nematode-elicited macrophages (NeM phi), that display IL-4-dependent features such as the expression of arginase 1, RELM-alpha (resistin-like molecule alpha), and Ym1. Since increasing evidence suggests that macrophages show functional adaptivity, the response of NeM phi to proinflammatory Th1-activating signals was investigated to determine whether a switch between alternative and classical activation could occur in macrophages differentiated in an in vivo infection setting. Despite the long-term exposure to Th2 cytokines and antiinflammatory signals in vivo, we found that NeM phi were not terminally differentiated but could develop a more classically activated phenotype in response to LPS and IFN-gamma. This was reflected by a switch in the enzymatic pathway for arginine metabolism from arginase to inducible NO synthase and the reduced expression of RELM-alpha and Ym1. Furthermore, this enabled NeM phi to become antimicrobial, as LPS/IFN-gamma-treated NeM phi produced NO that mediated killing of Leishmania mexicana. However, the adaptation to antimicrobial function did not extend to key regulatory pathways, such as IL-12 production, which remained unaltered. The Journal of Immunology, 2009, 182: 3084-3094.	72	74	2009	11	10.4049/jimmunol.0803463	Immunology
Spontaneous pneumomediastinum: A comparative study and review of the literature. Background. Spontaneous pneumomediastinum (SPM) is an unusual occurrence with few cases reported. It is seen after intrathoracic pressure changes leading to alveolar rupture and dissection of air along the tracheobronchial tree. This study was undertaken to provide a thorough clinical and radiologic analysis of this patient population. Methods. A retrospective comparative analysis was performed on patients with SPM over 12 years. Patient demographics, clinical presentation, and radiographic and diagnostic studies were recorded. A clinical and radiologic comparison was performed with secondary pneumomediastinum. Results. Seventy-four patients were identified with a diagnosis of pneumomediastinum. A total of 28 patients with SPM were identified. The major initial complaints were chest pain (54%), shortness of breath (39%), and subcutaneous emphysema (32%). The main triggering events were emesis (36%) and asthma flare-ups (21%). No apparent triggering event was noted in 21% of patients. Chest radiograph was diagnostic in 69%; computed tomography was required in 31%. Esophagram, esophagoscopy, and bronchoscopy were performed on an individual basis and were invariably negative. When compared with secondary pneumomediastinum, SPM is more likely to be discovered by chest radiography, has a lower incidence of pneumothorax and pleural effusion, requires a shorter hospital stay, and has no associated mortality. Conclusions. Spontaneous pneumomediastinum is a benign condition that often presents with chest pain or dyspnea. It can develop without a triggering event and with no findings on chest radiography. Treatment is expectant and recurrence is low. Secondary causes must be ruled out to avoid an unfavorable outcome.. adult patients| experience.	SEP-2008	adult patients| experience	Caceres, M; Ali, SZ; Braud, R; Weiman, D; Garrett, HE	Spontaneous pneumomediastinum: A comparative study and review of the literature		ANNALS OF THORACIC SURGERY		ADULT PATIENTS; EXPERIENCE	Background. Spontaneous pneumomediastinum (SPM) is an unusual occurrence with few cases reported. It is seen after intrathoracic pressure changes leading to alveolar rupture and dissection of air along the tracheobronchial tree. This study was undertaken to provide a thorough clinical and radiologic analysis of this patient population. Methods. A retrospective comparative analysis was performed on patients with SPM over 12 years. Patient demographics, clinical presentation, and radiographic and diagnostic studies were recorded. A clinical and radiologic comparison was performed with secondary pneumomediastinum. Results. Seventy-four patients were identified with a diagnosis of pneumomediastinum. A total of 28 patients with SPM were identified. The major initial complaints were chest pain (54%), shortness of breath (39%), and subcutaneous emphysema (32%). The main triggering events were emesis (36%) and asthma flare-ups (21%). No apparent triggering event was noted in 21% of patients. Chest radiograph was diagnostic in 69%; computed tomography was required in 31%. Esophagram, esophagoscopy, and bronchoscopy were performed on an individual basis and were invariably negative. When compared with secondary pneumomediastinum, SPM is more likely to be discovered by chest radiography, has a lower incidence of pneumothorax and pleural effusion, requires a shorter hospital stay, and has no associated mortality. Conclusions. Spontaneous pneumomediastinum is a benign condition that often presents with chest pain or dyspnea. It can develop without a triggering event and with no findings on chest radiography. Treatment is expectant and recurrence is low. Secondary causes must be ruled out to avoid an unfavorable outcome.	20	74	2008	5	10.1016/j.athoracsur.2008.04.067	Cardiovascular System & Cardiology; Respiratory System; Surgery
Evaluation of a low-cost electrostatic dust fall collector for indoor air endotoxin exposure assessment. Exposure to endotoxin in home environments has become a key issue in asthma and allergy research. Most studies have analyzed floor or mattress dust endotoxin, but its validity as a proxy for airborne exposure is unknown, while active airborne dust sampling is not feasible in large-scale population studies because of logistic and financial limitations. We therefore developed and evaluated a simple passive airborne dust collection method for airborne endotoxin exposure assessment. We explored an electrostatic dust fall collector (EDC), consisting of a 42- by 29.6-cm-sized folder with four electrostatic cloths exposed to the air. The EDC was tested during two 14-day periods in seven nonfarm and nine farm homes and in farm stables. In parallel, active airborne dust sampling was performed with Harvard impactors and floor dust collected by vacuuming, using nylon sampling socks. The endotoxin levels could be measured in all EDC cloth extracts. The levels (in EU/m(2)) between EDCs used simultaneously or in different sampling periods in the same home correlated strongly (r > 0.8). EDC endotoxin also correlated moderately to strongly (r = 0.6 to 0.8) with the endotoxin measured by active airborne dust sampling and living room floor dust sampling and-in farm homes-with the endotoxin captured by the EDC in stables. In contrast, endotoxin levels measured by floor dust sampling showed only a poor correlation with the levels measured by active airborne dust sampling. We therefore conclude that measuring endotoxin levels with the EDC is a valid measure of average airborne endotoxin exposure, while reproducibility over time is at least equivalent to that of reservoir dust analyses.. house-dust| airborne endotoxin| sampling methods| allergen| mite| cat| components| children| homes.	SEP-2008	house-dust| airborne endotoxin| sampling methods| allergen| mite| cat| components| children| homes	Noss, I; Wouters, IM; Visser, M; Heederik, DJJ; Thorne, PS; Brunekreef, B; Doekes, G	Evaluation of a low-cost electrostatic dust fall collector for indoor air endotoxin exposure assessment		APPLIED AND ENVIRONMENTAL MICROBIOLOGY		HOUSE-DUST; AIRBORNE ENDOTOXIN; SAMPLING METHODS; ALLERGEN; MITE; CAT; COMPONENTS; CHILDREN; HOMES	Exposure to endotoxin in home environments has become a key issue in asthma and allergy research. Most studies have analyzed floor or mattress dust endotoxin, but its validity as a proxy for airborne exposure is unknown, while active airborne dust sampling is not feasible in large-scale population studies because of logistic and financial limitations. We therefore developed and evaluated a simple passive airborne dust collection method for airborne endotoxin exposure assessment. We explored an electrostatic dust fall collector (EDC), consisting of a 42- by 29.6-cm-sized folder with four electrostatic cloths exposed to the air. The EDC was tested during two 14-day periods in seven nonfarm and nine farm homes and in farm stables. In parallel, active airborne dust sampling was performed with Harvard impactors and floor dust collected by vacuuming, using nylon sampling socks. The endotoxin levels could be measured in all EDC cloth extracts. The levels (in EU/m(2)) between EDCs used simultaneously or in different sampling periods in the same home correlated strongly (r > 0.8). EDC endotoxin also correlated moderately to strongly (r = 0.6 to 0.8) with the endotoxin measured by active airborne dust sampling and living room floor dust sampling and-in farm homes-with the endotoxin captured by the EDC in stables. In contrast, endotoxin levels measured by floor dust sampling showed only a poor correlation with the levels measured by active airborne dust sampling. We therefore conclude that measuring endotoxin levels with the EDC is a valid measure of average airborne endotoxin exposure, while reproducibility over time is at least equivalent to that of reservoir dust analyses.	24	74	2008	7	10.1128/AEM.00619-08	Biotechnology & Applied Microbiology; Microbiology
Size distribution and total number concentration of ultrafine and accumulation mode particles and hospital admissions in children and the elderly in Copenhagen, Denmark. Objectives: To study the association between short-term exposure to ultrafine particles and morbidity in Copenhagen, Denmark. Methods: We studied the association between urban background levels of the total number concentration of particles (NCtot, 6-700 nm in diameter) measured at a single site (15 May 2001 to 31 December 2004) and hospital admissions due to cardiovascular (CVD) and respiratory disease (RD) in the elderly (age >= 65 years), and due to asthma in children (age 5-18 years). We examined these associations in the presence of PM10, PM2.5 (particulate matter < 10 and 2.5 mu m in diameter, respectively) and ambient gasses. We utilised data on size distribution to calculate NCtot for four modes with median diameters 12, 23, 57 and 212 nm, and NC100 (number concentration of particles < 100 nm in diameter) and examined their associations with health outcomes. We used a time series Poisson generalised additive model adjusted for overdispersion, season, day of the week, public holidays, school holidays, influenza, pollen and meteorology, with up to 5 days' lagged exposure. Results and conclusions: The adverse health effects of particulate matter on CVD and RD hospital admissions in the elderly were mainly mediated by PM10 and accumulation mode particles with lack of effects for NC100. For paediatric asthma, accumulation mode particles, NC100 and nitrogen oxides (mainly from traffic related sources) were relevant, whereas PM10 appeared to have little effect. Our results suggest that particle volume/mass from long-range transported air pollution is relevant for CVD and RD admissions in the elderly, and possibly particle numbers from traffic sources for paediatric asthma.. particulate air-pollution| coronary-heart-disease| 5 european cities| myocardial-infarction| exposure assessment| urban air| fine| ambient| health| indoor.	JUL-2008	particulate air-pollution| coronary-heart-disease| 5 european cities| myocardial-infarction| exposure assessment| urban air| fine| ambient| health| indoor	Andersen, ZJ; Wahlin, P; Raaschou-Nielsen, O; Ketzel, M; Scheike, T; Loft, S	Size distribution and total number concentration of ultrafine and accumulation mode particles and hospital admissions in children and the elderly in Copenhagen, Denmark		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		PARTICULATE AIR-POLLUTION; CORONARY-HEART-DISEASE; 5 EUROPEAN CITIES; MYOCARDIAL-INFARCTION; EXPOSURE ASSESSMENT; URBAN AIR; FINE; AMBIENT; HEALTH; INDOOR	Objectives: To study the association between short-term exposure to ultrafine particles and morbidity in Copenhagen, Denmark. Methods: We studied the association between urban background levels of the total number concentration of particles (NCtot, 6-700 nm in diameter) measured at a single site (15 May 2001 to 31 December 2004) and hospital admissions due to cardiovascular (CVD) and respiratory disease (RD) in the elderly (age >= 65 years), and due to asthma in children (age 5-18 years). We examined these associations in the presence of PM10, PM2.5 (particulate matter < 10 and 2.5 mu m in diameter, respectively) and ambient gasses. We utilised data on size distribution to calculate NCtot for four modes with median diameters 12, 23, 57 and 212 nm, and NC100 (number concentration of particles < 100 nm in diameter) and examined their associations with health outcomes. We used a time series Poisson generalised additive model adjusted for overdispersion, season, day of the week, public holidays, school holidays, influenza, pollen and meteorology, with up to 5 days' lagged exposure. Results and conclusions: The adverse health effects of particulate matter on CVD and RD hospital admissions in the elderly were mainly mediated by PM10 and accumulation mode particles with lack of effects for NC100. For paediatric asthma, accumulation mode particles, NC100 and nitrogen oxides (mainly from traffic related sources) were relevant, whereas PM10 appeared to have little effect. Our results suggest that particle volume/mass from long-range transported air pollution is relevant for CVD and RD admissions in the elderly, and possibly particle numbers from traffic sources for paediatric asthma.	44	74	2008	9	10.1136/oem.2007.033290	Public, Environmental & Occupational Health
Genetic susceptibility to the respiratory effects of air pollution. There is large variation between individuals in their response to air pollutants. This review summarises the existing evidence that genetic factors influence the mechanisms of lung injury caused by air pollutants. Genetic association studies have compared the adverse effects of air pollutants between subjects with specific genotypes in biologically relevant genes. In human studies of ozone exposure, polymorphisms in oxidative stress genes (NQO1, GSTM1, GSTP1) modify respiratory symptoms, lung function, biomarkers and risk of asthma. Inflammatory gene polymorphisms (TNF) influence the lung function response to ozone, and the effect of different levels of ozone on the development of asthma. Polymorphisms in oxidative stress genes (GSTM1, GSTP1) alter the response to combined exposure to ragweed pollen and diesel exhaust particles. Importantly, polymorphisms in an oxidative stress gene (GSTM1) have predicted patients with asthma who benefit from antioxidant supplementation in Mexico City, which has chronically high ozone exposure. Genetic linkage studies of families have not been feasible for studying the effects of air pollution in humans, but some progress has been made with pedigrees of specially bred mice, in identifying chromosomal regions linked to effects of ozone or particles. A high priority now, in addition to avoiding exposure in the most susceptible people, is to clearly identify the most effective and safe chemopreventive agents for individuals who are genetically susceptible to the adverse effects of air pollution (eg, antioxidants to be taken during high ozone levels).. bronchial epithelial-cells| diesel exhaust particles| acute lung injury| obstructive pulmonary-disease| bronchoalveolar lavage fluid| repeated ozone exposures| s-transferase m1| oxidative stress| nitrogen-dioxide| particulate air.	JUN-2008	bronchial epithelial-cells| diesel exhaust particles| acute lung injury| obstructive pulmonary-disease| bronchoalveolar lavage fluid| repeated ozone exposures| s-transferase m1| oxidative stress| nitrogen-dioxide| particulate air	Yang, IA; Fong, KM; Zimmerman, PV; Holgate, ST; Holloway, JW	Genetic susceptibility to the respiratory effects of air pollution		THORAX		BRONCHIAL EPITHELIAL-CELLS; DIESEL EXHAUST PARTICLES; ACUTE LUNG INJURY; OBSTRUCTIVE PULMONARY-DISEASE; BRONCHOALVEOLAR LAVAGE FLUID; REPEATED OZONE EXPOSURES; S-TRANSFERASE M1; OXIDATIVE STRESS; NITROGEN-DIOXIDE; PARTICULATE AIR	There is large variation between individuals in their response to air pollutants. This review summarises the existing evidence that genetic factors influence the mechanisms of lung injury caused by air pollutants. Genetic association studies have compared the adverse effects of air pollutants between subjects with specific genotypes in biologically relevant genes. In human studies of ozone exposure, polymorphisms in oxidative stress genes (NQO1, GSTM1, GSTP1) modify respiratory symptoms, lung function, biomarkers and risk of asthma. Inflammatory gene polymorphisms (TNF) influence the lung function response to ozone, and the effect of different levels of ozone on the development of asthma. Polymorphisms in oxidative stress genes (GSTM1, GSTP1) alter the response to combined exposure to ragweed pollen and diesel exhaust particles. Importantly, polymorphisms in an oxidative stress gene (GSTM1) have predicted patients with asthma who benefit from antioxidant supplementation in Mexico City, which has chronically high ozone exposure. Genetic linkage studies of families have not been feasible for studying the effects of air pollution in humans, but some progress has been made with pedigrees of specially bred mice, in identifying chromosomal regions linked to effects of ozone or particles. A high priority now, in addition to avoiding exposure in the most susceptible people, is to clearly identify the most effective and safe chemopreventive agents for individuals who are genetically susceptible to the adverse effects of air pollution (eg, antioxidants to be taken during high ozone levels).	100	74	2008	9	10.1136/thx.2007.079426	Respiratory System
Neonatal antibiotic treatment is a risk factor for early wheezing. OBJECTIVE. The use of antibiotics in infancy and subsequent changes in the intestinal bacterial flora have been discussed as risk factors for the development of asthma. However, it has been difficult to exclude the possibility that antibiotics have been given in early episodes of wheezing. As a result, there has been a risk of reverse causation. To minimize the risk of reverse causation, we have focused on the effect of antibiotics that are already administered on the neonatal ward. METHODS. In a cohort study of infants born in western Sweden in 2003, we studied the development of wheezing. The families of the infants were randomly selected and sent a questionnaire at child ages 6 and 12 months. The response rate was 68.5% to the 6-month questionnaire and 68.9% to the 12-month questionnaire. RESULTS. At 12 months, 20.2% of infants had had 1 or more episodes of wheezing, and 5.3% had had 3 or more episodes. Inhaled corticosteroids had been taken by 4.1% of the infants. Independent risk factors for wheezing disorder treated with inhaled corticosteroids were neonatal antibiotic treatment, male gender, gestational age of <37 weeks, having a mother with asthma, having a sibling with asthma or eczema, and breastfeeding for <5 months. CONCLUSIONS. Treatment with antibiotics in the neonatal period was an independent risk factor for wheezing that was treated with inhaled corticosteroids at 12 months of age. These results indirectly support the hypothesis that an alteration in the intestinal flora can increase the risk of subsequent wheezing.. antibiotics| cohort studies| infant| wheezing|tobacco-smoke exposure| early-childhood| 1st year| birth cohort| allergic disease| asthma| life| infancy| age| infections.	APR-2008	antibiotics| cohort studies| infant| wheezing|tobacco-smoke exposure| early-childhood| 1st year| birth cohort| allergic disease| asthma| life| infancy| age| infections	Alm, B; Erdes, L; Mollborg, P; Pettersson, R; Norvenius, SG; Aberg, N; Wennergren, G	Neonatal antibiotic treatment is a risk factor for early wheezing		PEDIATRICS	antibiotics; cohort studies; infant; wheezing	TOBACCO-SMOKE EXPOSURE; EARLY-CHILDHOOD; 1ST YEAR; BIRTH COHORT; ALLERGIC DISEASE; ASTHMA; LIFE; INFANCY; AGE; INFECTIONS	OBJECTIVE. The use of antibiotics in infancy and subsequent changes in the intestinal bacterial flora have been discussed as risk factors for the development of asthma. However, it has been difficult to exclude the possibility that antibiotics have been given in early episodes of wheezing. As a result, there has been a risk of reverse causation. To minimize the risk of reverse causation, we have focused on the effect of antibiotics that are already administered on the neonatal ward. METHODS. In a cohort study of infants born in western Sweden in 2003, we studied the development of wheezing. The families of the infants were randomly selected and sent a questionnaire at child ages 6 and 12 months. The response rate was 68.5% to the 6-month questionnaire and 68.9% to the 12-month questionnaire. RESULTS. At 12 months, 20.2% of infants had had 1 or more episodes of wheezing, and 5.3% had had 3 or more episodes. Inhaled corticosteroids had been taken by 4.1% of the infants. Independent risk factors for wheezing disorder treated with inhaled corticosteroids were neonatal antibiotic treatment, male gender, gestational age of <37 weeks, having a mother with asthma, having a sibling with asthma or eczema, and breastfeeding for <5 months. CONCLUSIONS. Treatment with antibiotics in the neonatal period was an independent risk factor for wheezing that was treated with inhaled corticosteroids at 12 months of age. These results indirectly support the hypothesis that an alteration in the intestinal flora can increase the risk of subsequent wheezing.	28	74	2008	6	10.1542/peds.2007-1232	Pediatrics
Ambient particle source apportionment and daily hospital admissions among children and elderly in Copenhagen. An association between particulate air pollution and morbidity and mortality is well established. However, little is known about which sources of particulate matter contribute most to the adverse health effects. Identification of responsible sources would merit more effficient control. For a 6-year period ( 01 January 1999 to 31 December 2004), we examined associations between urban background PM10 in the presence of gaseous pollutants ( CO, NO2) and hospital admissions due to cardiovascular and respiratory disease in the elderly (age >= 65), and asthma in children (age 5-18) in Copenhagen, Denmark. We further studied associations between fractions of PM10 assigned to six sources (biomass, secondary, oil, crustal, sea salt, and vehicle) and admissions during a 11/2 -year campaign. We used Poisson generalized additive time-series model adjusted for season, day of the week, public holidays, influenza epidemics, grass pollen, school holidays, and meteorology, with up to 5 days lagged air pollution exposure. We found positive associations between PM10 and the three health outcomes, with strongest associations for asthma. The PM10 effect remained robustin the presence of CO and NO2. We found different PM10 sources to be variably associated with different outcomes: crustal and secondary sources showed strongest associations with cardiovascular, biomass with respiratory, and vehicle with asthma admissions. These novel results may merit future research of potential mechanism, whereas at present, no single PM10 source can be attributed to all morbidity.. pm(10)| source apportionment| hospital admissions| cardiovascular| respiratory| asthma|pm source apportionment| particulate air-pollution| daily mortality| fine particles| respiratory-diseases| childhood asthma| european cities| receptor model| health| associations.	NOV-2007	pm(10)| source apportionment| hospital admissions| cardiovascular| respiratory| asthma|pm source apportionment| particulate air-pollution| daily mortality| fine particles| respiratory-diseases| childhood asthma| european cities| receptor model| health| associations	Andersen, ZJ; Wahlin, P; Raaschou-Nielsen, O; Scheike, T; Loft, S	Ambient particle source apportionment and daily hospital admissions among children and elderly in Copenhagen		JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY	pM(10); source apportionment; hospital admissions; cardiovascular; respiratory; asthma	PM SOURCE APPORTIONMENT; PARTICULATE AIR-POLLUTION; DAILY MORTALITY; FINE PARTICLES; RESPIRATORY-DISEASES; CHILDHOOD ASTHMA; EUROPEAN CITIES; RECEPTOR MODEL; HEALTH; ASSOCIATIONS	An association between particulate air pollution and morbidity and mortality is well established. However, little is known about which sources of particulate matter contribute most to the adverse health effects. Identification of responsible sources would merit more effficient control. For a 6-year period ( 01 January 1999 to 31 December 2004), we examined associations between urban background PM10 in the presence of gaseous pollutants ( CO, NO2) and hospital admissions due to cardiovascular and respiratory disease in the elderly (age >= 65), and asthma in children (age 5-18) in Copenhagen, Denmark. We further studied associations between fractions of PM10 assigned to six sources (biomass, secondary, oil, crustal, sea salt, and vehicle) and admissions during a 11/2 -year campaign. We used Poisson generalized additive time-series model adjusted for season, day of the week, public holidays, influenza epidemics, grass pollen, school holidays, and meteorology, with up to 5 days lagged air pollution exposure. We found positive associations between PM10 and the three health outcomes, with strongest associations for asthma. The PM10 effect remained robustin the presence of CO and NO2. We found different PM10 sources to be variably associated with different outcomes: crustal and secondary sources showed strongest associations with cardiovascular, biomass with respiratory, and vehicle with asthma admissions. These novel results may merit future research of potential mechanism, whereas at present, no single PM10 source can be attributed to all morbidity.	43	74	2007	12	10.1038/sj.jes.7500546	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Allergic airway responses in obese mice. Rationale: Epidemiologic data indicate an increased incidence of asthma in the obese. Objectives: To determine whether obese mice exhibit augmented pulmonary responses after allergen sensitization and challenge. Methods: Lean, wild-type (C57BL/6), obese ob/ob, and obese db/db mice were sensitized to ovalbumin (OVA), and then challenged with aerosolized OVA or phosphate-buffered saline (PBS). Changes in total pulmonary resistance (RL) induced by intravenous methacholine were measured by forced oscillation. Blood was collected, bronchoalveolar lavage (BAL) was performed, and lungs were harvested for measurement of cytokine expression by real-time reverse transcription-polymerase chain reaction. Measurements and Main Results: OVA challenge increased baseline R-L in ob/ob, but not wild-type, mice, and airway responsiveness was greater in ob/ob than wild-type mice, regardless of the challenge. Compared with PBS, OVA challenge caused an increase in the number of BAL fluid (BALF) cells, an increase in lung Th2 cytokine expression, and an increase in serum IgE. Significantly fewer BALF cells were recovered from OVA-challenged ob/ob versus wild-type mice, whereas serum IgE levels were elevated significantly more in ob/ob versus wild-type mice. BALIF and lung Th2 cytokine expression was not different in ob/ob versus wild-type mice. Airway responsiveness was greater in db/db versus wild-type mice, regardless of the challenge, and OVA caused airway hyperresponsiveness in db/db but not wild-type mice, despite reduced BALF cells in OVA-challenged db/db versus wild-type mice. Conclusions: These results demonstrate that obesity enhances OVA-induced changes in pulmonary resistance and serum IgE and that these changes are not the result of increased Th2 type airway inflammation.. airway responsiveness| eosinophil| immunoglobulin e| interleukin-13| pulmonary resistance|body-mass index| necrosis-factor-alpha| acute ozone exposure| c-reactive protein| respiratory symptoms| pulmonary responses| insulin-resistance| weight-reduction| asthma| inflammation.	OCT 1-2007	airway responsiveness| eosinophil| immunoglobulin e| interleukin-13| pulmonary resistance|body-mass index| necrosis-factor-alpha| acute ozone exposure| c-reactive protein| respiratory symptoms| pulmonary responses| insulin-resistance| weight-reduction| asthma| inflammation	Johnston, RA; Zhu, M; Rivera-Sanchez, YM; Lu, FL; Theman, TA; Flynt, L; Shore, SA	Allergic airway responses in obese mice		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	airway responsiveness; eosinophil; immunoglobulin E; interleukin-13; pulmonary resistance	BODY-MASS INDEX; NECROSIS-FACTOR-ALPHA; ACUTE OZONE EXPOSURE; C-REACTIVE PROTEIN; RESPIRATORY SYMPTOMS; PULMONARY RESPONSES; INSULIN-RESISTANCE; WEIGHT-REDUCTION; ASTHMA; INFLAMMATION	Rationale: Epidemiologic data indicate an increased incidence of asthma in the obese. Objectives: To determine whether obese mice exhibit augmented pulmonary responses after allergen sensitization and challenge. Methods: Lean, wild-type (C57BL/6), obese ob/ob, and obese db/db mice were sensitized to ovalbumin (OVA), and then challenged with aerosolized OVA or phosphate-buffered saline (PBS). Changes in total pulmonary resistance (RL) induced by intravenous methacholine were measured by forced oscillation. Blood was collected, bronchoalveolar lavage (BAL) was performed, and lungs were harvested for measurement of cytokine expression by real-time reverse transcription-polymerase chain reaction. Measurements and Main Results: OVA challenge increased baseline R-L in ob/ob, but not wild-type, mice, and airway responsiveness was greater in ob/ob than wild-type mice, regardless of the challenge. Compared with PBS, OVA challenge caused an increase in the number of BAL fluid (BALF) cells, an increase in lung Th2 cytokine expression, and an increase in serum IgE. Significantly fewer BALF cells were recovered from OVA-challenged ob/ob versus wild-type mice, whereas serum IgE levels were elevated significantly more in ob/ob versus wild-type mice. BALIF and lung Th2 cytokine expression was not different in ob/ob versus wild-type mice. Airway responsiveness was greater in db/db versus wild-type mice, regardless of the challenge, and OVA caused airway hyperresponsiveness in db/db but not wild-type mice, despite reduced BALF cells in OVA-challenged db/db versus wild-type mice. Conclusions: These results demonstrate that obesity enhances OVA-induced changes in pulmonary resistance and serum IgE and that these changes are not the result of increased Th2 type airway inflammation.	65	74	2007	9	10.1164/rccm.200702-323OC	General & Internal Medicine; Respiratory System
Comparative overview of indoor air quality in Antwerp, Belgium. This comprehensive study, a first in Belgium, aimed at characterizing the residential and school indoor air quality of subgroups that took part in the European Community Respiratory Health Survey and the International Study of Asthma and Allergy in Childhood [Masoli M, Fabian D, Holt S, Beasley R. Global Burden of Asthma, Medical Research Institute of New Zealand, University of Southampton; 2004.] questionnaire-based asthma and related illnesses studies. The principal aim was to perform a base-line study to assess the indoor air quality in Antwerp in terms of various gaseous and particulate pollutants. Secondly, it aimed to establish correlations between these pollutants investigated, the pollutant levels in the indoor and outdoor micro-environments, findings of the previous questionnaire-based studies and an epidemiological study which ran in conjunction with this study. Lastly, these results were compared and evaluated with current indoor and ambient guidelines in various countries This paper presents selected results on PM1, PM2.5 and PM 10 mass concentrations and elemental C estimates as black smoke, as well as gaseous NO, SO2, O-3 and BTEX concentrations of 18 residences and 27 schools. These are related to current guidelines of Flanders, Germany, Norway, China and Canada and evaluated with reference to selected similar studies. It was found that indoor sources such as tobacco smoking and carpets, the latter causing re-suspension of dust, are responsible for elevated indoor respirable particulate matter and place school children and residents at risk. Both PM2.5 and PM10 equalled or exceeded the current guidelines adopted by Flanders, noting that 12-h and 24-h PM2.5 were compared with an annual limit value. Indoor and ambient NO2 concentrations in the school campaign were higher than the annual EU ambient norm. The other studied pollutant levels were below the current guidelines. (c) 2007 Elsevier Ltd. All rights reserved.. indoor air quality| pm1| pm2.5| pm10| gaseous pollutants|suspended particle exposures| environmental tobacco-smoke| peak expiratory flow| long-term exposure| hong-kong| particulate matter| respiratory symptoms| nitrogen-dioxide| indoor/outdoor relationships| elemental composition.	AUG-2007	indoor air quality| pm1| pm2.5| pm10| gaseous pollutants|suspended particle exposures| environmental tobacco-smoke| peak expiratory flow| long-term exposure| hong-kong| particulate matter| respiratory symptoms| nitrogen-dioxide| indoor/outdoor relationships| elemental composition	Stranger, M; Potgieter-Vermaak, SS; Van Grieken, R	Comparative overview of indoor air quality in Antwerp, Belgium		ENVIRONMENT INTERNATIONAL	indoor air quality; PM1; PM2.5; PM10; gaseous pollutants	SUSPENDED PARTICLE EXPOSURES; ENVIRONMENTAL TOBACCO-SMOKE; PEAK EXPIRATORY FLOW; LONG-TERM EXPOSURE; HONG-KONG; PARTICULATE MATTER; RESPIRATORY SYMPTOMS; NITROGEN-DIOXIDE; INDOOR/OUTDOOR RELATIONSHIPS; ELEMENTAL COMPOSITION	This comprehensive study, a first in Belgium, aimed at characterizing the residential and school indoor air quality of subgroups that took part in the European Community Respiratory Health Survey and the International Study of Asthma and Allergy in Childhood [Masoli M, Fabian D, Holt S, Beasley R. Global Burden of Asthma, Medical Research Institute of New Zealand, University of Southampton; 2004.] questionnaire-based asthma and related illnesses studies. The principal aim was to perform a base-line study to assess the indoor air quality in Antwerp in terms of various gaseous and particulate pollutants. Secondly, it aimed to establish correlations between these pollutants investigated, the pollutant levels in the indoor and outdoor micro-environments, findings of the previous questionnaire-based studies and an epidemiological study which ran in conjunction with this study. Lastly, these results were compared and evaluated with current indoor and ambient guidelines in various countries This paper presents selected results on PM1, PM2.5 and PM 10 mass concentrations and elemental C estimates as black smoke, as well as gaseous NO, SO2, O-3 and BTEX concentrations of 18 residences and 27 schools. These are related to current guidelines of Flanders, Germany, Norway, China and Canada and evaluated with reference to selected similar studies. It was found that indoor sources such as tobacco smoking and carpets, the latter causing re-suspension of dust, are responsible for elevated indoor respirable particulate matter and place school children and residents at risk. Both PM2.5 and PM10 equalled or exceeded the current guidelines adopted by Flanders, noting that 12-h and 24-h PM2.5 were compared with an annual limit value. Indoor and ambient NO2 concentrations in the school campaign were higher than the annual EU ambient norm. The other studied pollutant levels were below the current guidelines. (c) 2007 Elsevier Ltd. All rights reserved.	47	74	2007	9	10.1016/j.envint.2007.02.014	Environmental Sciences & Ecology
Omega-3 and omega-6 fatty acid exposure from early life does not affect atopy and asthma at age 5 years. Background: The Childhood Asthma Prevention Study was a randomized controlled trial conducted in children with a family history of asthma in whom omega-3 fatty acid supplementation and restriction of dietary omega-6 fatty acids did not prevent asthma, eczema, or atopy at age 5 years. Objective: We sought to examine the relation of all measures of omega-3 and omega-6 polyunsaturated fatty acids with outcomes at age 5 years in the whole birth cohort, regardless of randomization group. Methods: Plasma fatty acids were measured at 18 months, 3 years, and 5 years. Compliance with the fatty acid supplements was estimated every 6 months. Dietary intake was assessed at 18 months by means of weighed-food record and at 3 years by means of food-frequency questionnaire. At age 5 years, 516 children were examined for wheeze and eczema (questionnaire) and atopy (skin prick tests, n = 488). Multiple logistic regression was used to evaluate associations between exposures and outcomes. Results: Plasma levels of omega-3 or omega-6 fatty acids were not associated with wheeze, eczema, or atopy at age 5 years (P = .11-.96). Overall, fatty acid exposure, measured as plasma levels, dietary intake, and compliance with supplements, was not associated with any respiratory or allergic outcomes (P =.35-.59). Conclusion: This observational analysis of the cohort, using the full range of observed variation in omega-3 and omega-6 fatty acid exposure, supports the negative findings of the randomized controlled trial. Clinical implications: Modification of dietary polyunsaturated fatty acids in early childhood is not helpful in preventing atopy and asthma.. asthma| allergy and immunology| birth cohort| child| eczema| omega-3 fatty acids| omega-6 fatty acids| primary prevention|childhood asthma| children| dietary| adults| risk| prevention| trial| fish.	JUN-2007	asthma| allergy and immunology| birth cohort| child| eczema| omega-3 fatty acids| omega-6 fatty acids| primary prevention|childhood asthma| children| dietary| adults| risk| prevention| trial| fish	Almqvist, C; Garden, F; Xuan, W; Mihrshahi, S; Leeder, SR; Oddy, W; Webb, K; Marks, GB	Omega-3 and omega-6 fatty acid exposure from early life does not affect atopy and asthma at age 5 years		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; allergy and immunology; birth cohort; child; eczema; omega-3 fatty acids; omega-6 fatty acids; primary prevention	CHILDHOOD ASTHMA; CHILDREN; DIETARY; ADULTS; RISK; PREVENTION; TRIAL; FISH	Background: The Childhood Asthma Prevention Study was a randomized controlled trial conducted in children with a family history of asthma in whom omega-3 fatty acid supplementation and restriction of dietary omega-6 fatty acids did not prevent asthma, eczema, or atopy at age 5 years. Objective: We sought to examine the relation of all measures of omega-3 and omega-6 polyunsaturated fatty acids with outcomes at age 5 years in the whole birth cohort, regardless of randomization group. Methods: Plasma fatty acids were measured at 18 months, 3 years, and 5 years. Compliance with the fatty acid supplements was estimated every 6 months. Dietary intake was assessed at 18 months by means of weighed-food record and at 3 years by means of food-frequency questionnaire. At age 5 years, 516 children were examined for wheeze and eczema (questionnaire) and atopy (skin prick tests, n = 488). Multiple logistic regression was used to evaluate associations between exposures and outcomes. Results: Plasma levels of omega-3 or omega-6 fatty acids were not associated with wheeze, eczema, or atopy at age 5 years (P = .11-.96). Overall, fatty acid exposure, measured as plasma levels, dietary intake, and compliance with supplements, was not associated with any respiratory or allergic outcomes (P =.35-.59). Conclusion: This observational analysis of the cohort, using the full range of observed variation in omega-3 and omega-6 fatty acid exposure, supports the negative findings of the randomized controlled trial. Clinical implications: Modification of dietary polyunsaturated fatty acids in early childhood is not helpful in preventing atopy and asthma.	17	74	2007	7	10.1016/j.jaci.2007.01.046	Allergy; Immunology
Health effects of airborne exposures from concentrated animal feeding operations. Toxic gases, vapors, and particles are emitted from concentrated animal feeding operations (CAFOs) into the general environment. These include ammonia, hydrogen sulfide, carbon dioxide, malodorous vapors, and particles contaminated with a wide range of microorganisms. Little is known about the health risks of exposure to these agents for people living in the surrounding areas. Malodor is one of the predominant concerns, and there is evidence that psychophysiologic changes may occur as a result of exposure to malodorous compounds. There is a paucity of data regarding community adverse health effects related to low-level gas and particulate emissions. Most information comes from studies among workers in CAFO installations. Research over the last decades has shown that microbial exposures, especially endotoxin exposure, are related to deleterious respiratory health effects, of which cross-shift lung function decline and accelerated decline over time are the most pronounced effects. Studies in naive subjects and workers have shown respiratory inflammatory responses related to the microbial load. This working group, which was part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards-Searching for Solutions, concluded that there is a great need to evaluate health effects from exposures to the toxic gases, vapors, and particles emitted into the general environment by CAFOs. Research should focus not only on nuisance and odors but also on potential health effects from microbial exposures, concentrating on susceptible subgroups, especially asthmatic children and the elderly, since these exposures have been shown to be related to respiratory health effects among workers in CAFOs.. air quality| asthma| biological agents| endotoxin| inflammation| odor| poultry| swine|swine confinement buildings| in-house dust| endotoxin exposure| lung-function| occupational asthma| respiratory health| hay-fever| environmental endotoxin| allergic sensitization| farmers children.	FEB-2007	air quality| asthma| biological agents| endotoxin| inflammation| odor| poultry| swine|swine confinement buildings| in-house dust| endotoxin exposure| lung-function| occupational asthma| respiratory health| hay-fever| environmental endotoxin| allergic sensitization| farmers children	Heederik, D; Sigsgaard, T; Thorne, PS; Kline, JN; Avery, R; Bonlokke, JH; Chrischilles, EA; Dosman, JA; Duchaine, C; Kirkhorn, SR; Kulhankova, K; Merchant, JA	Health effects of airborne exposures from concentrated animal feeding operations		ENVIRONMENTAL HEALTH PERSPECTIVES	air quality; asthma; biological agents; endotoxin; inflammation; odor; poultry; swine	SWINE CONFINEMENT BUILDINGS; IN-HOUSE DUST; ENDOTOXIN EXPOSURE; LUNG-FUNCTION; OCCUPATIONAL ASTHMA; RESPIRATORY HEALTH; HAY-FEVER; ENVIRONMENTAL ENDOTOXIN; ALLERGIC SENSITIZATION; FARMERS CHILDREN	Toxic gases, vapors, and particles are emitted from concentrated animal feeding operations (CAFOs) into the general environment. These include ammonia, hydrogen sulfide, carbon dioxide, malodorous vapors, and particles contaminated with a wide range of microorganisms. Little is known about the health risks of exposure to these agents for people living in the surrounding areas. Malodor is one of the predominant concerns, and there is evidence that psychophysiologic changes may occur as a result of exposure to malodorous compounds. There is a paucity of data regarding community adverse health effects related to low-level gas and particulate emissions. Most information comes from studies among workers in CAFO installations. Research over the last decades has shown that microbial exposures, especially endotoxin exposure, are related to deleterious respiratory health effects, of which cross-shift lung function decline and accelerated decline over time are the most pronounced effects. Studies in naive subjects and workers have shown respiratory inflammatory responses related to the microbial load. This working group, which was part of the Conference on Environmental Health Impacts of Concentrated Animal Feeding Operations: Anticipating Hazards-Searching for Solutions, concluded that there is a great need to evaluate health effects from exposures to the toxic gases, vapors, and particles emitted into the general environment by CAFOs. Research should focus not only on nuisance and odors but also on potential health effects from microbial exposures, concentrating on susceptible subgroups, especially asthmatic children and the elderly, since these exposures have been shown to be related to respiratory health effects among workers in CAFOs.	60	74	2007	5	10.1289/ehp.8835	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Aerosolized red-tide toxins (brevetoxins) and asthma. Background: With the increasing incidence of asthma, there is increasing concern over environmental exposures that may trigger asthma exacerbations. Blooms of the marine microalgae, Karenia brevis, cause red titles (or harmful algal blooms) annually throughout the Gulf of Mexico. K brevis produces higlily potent natural polyether toxins, called brevetoxins, which are sodium channel blockers, and possibly histamine activators. In experimental animals, brevetoxins cause significant bronchoconstriction. In humans, a significant increase in self-reported respiratory symptoms has been described after recreational and occupational exposures to Florida red-tide aerosols, particularly among individuals with asthma. Methods: Before and after 1 h spent on beaches with and without an active K brevis red-tide exposure, 97 persons 12 years of age with physician-diagnosed asthma were evaluated by questionnaire and spirometry. Concomitant environmental monitoring, water and air sampling, and personal monitoring for brevetoxins were performed. Results: Participants were significantly more likely to report respiratory symptoms after K brevis red-tide aerosol exposure than before exposure. Participants demonstrated small, but statistically significant, decreases in FEV1, midexpiratory phase of forced expiratory, flow, and peak expiratory flow after exposure, particularly among those participants regularly using asthma medications. No significant differences were detected when there was no Florida red tide (ie, during nonexposure periods). Conclusions: This study demonstrated objectively measurable adverse changes in lung function from exposure to aerosolized Florida red-tide toxins in asthmatic subjects, particularly among those requiring regular therapy with asthma medications. Future studies will assess these susceptible subpopulations in more deptb,as well as the possible long-term effects of these toxins.. asthma| brevetoxins| harmful algal blooms| karenia brevis| red tides| sensitive populations| spirometry|air-pollution| marine aerosol| human exposure| florida| population| shellfish| events| brevis| health.	JAN-2007	asthma| brevetoxins| harmful algal blooms| karenia brevis| red tides| sensitive populations| spirometry|air-pollution| marine aerosol| human exposure| florida| population| shellfish| events| brevis| health	Fleming, LE; Kirkpatrick, B; Backer, LC; Beam, JA; Wanner, A; Reich, A; Zaias, J; Cheng, YS; Pierce, R; Naar, J; Abraham, WM; Baden, DG	Aerosolized red-tide toxins (brevetoxins) and asthma		CHEST	asthma; brevetoxins; harmful algal blooms; Karenia brevis; red tides; sensitive populations; spirometry	AIR-POLLUTION; MARINE AEROSOL; HUMAN EXPOSURE; FLORIDA; POPULATION; SHELLFISH; EVENTS; BREVIS; HEALTH	Background: With the increasing incidence of asthma, there is increasing concern over environmental exposures that may trigger asthma exacerbations. Blooms of the marine microalgae, Karenia brevis, cause red titles (or harmful algal blooms) annually throughout the Gulf of Mexico. K brevis produces higlily potent natural polyether toxins, called brevetoxins, which are sodium channel blockers, and possibly histamine activators. In experimental animals, brevetoxins cause significant bronchoconstriction. In humans, a significant increase in self-reported respiratory symptoms has been described after recreational and occupational exposures to Florida red-tide aerosols, particularly among individuals with asthma. Methods: Before and after 1 h spent on beaches with and without an active K brevis red-tide exposure, 97 persons 12 years of age with physician-diagnosed asthma were evaluated by questionnaire and spirometry. Concomitant environmental monitoring, water and air sampling, and personal monitoring for brevetoxins were performed. Results: Participants were significantly more likely to report respiratory symptoms after K brevis red-tide aerosol exposure than before exposure. Participants demonstrated small, but statistically significant, decreases in FEV1, midexpiratory phase of forced expiratory, flow, and peak expiratory flow after exposure, particularly among those participants regularly using asthma medications. No significant differences were detected when there was no Florida red tide (ie, during nonexposure periods). Conclusions: This study demonstrated objectively measurable adverse changes in lung function from exposure to aerosolized Florida red-tide toxins in asthmatic subjects, particularly among those requiring regular therapy with asthma medications. Future studies will assess these susceptible subpopulations in more deptb,as well as the possible long-term effects of these toxins.	38	74	2007	8	10.1378/chest.06-1830	General & Internal Medicine; Respiratory System
Influence of dog ownership and high endotoxin on wheezing and atopy during infancy. Background: Increased exposure to microbial products early in life may protect from development of atopic disorders in childhood. Few studies have examined the relationship of endotoxin exposure and pet ownership on atopy and wheezing during infancy. Objective: Evaluate relationships among high endotoxin exposure, pet ownership, atopy, and wheezing in high-risk infants. Methods: Infants (n = 532; mean age, 12.5 +/- 0.8 months) with at least 1 parent with confirmed atopy were recruited. A complete medical history and skin prick testing to foods and aeroallergens were performed at age 1 year. House dust samples were analyzed for endotoxin. Results: Prevalences of wheezing were not independently associated with dog or cat ownership or endotoxin levels. Percutaneous reactivity to at least 1 allergen was observed in 28.6% of infants. Univariate analyses showed significant associations of any wheezing, recurrent wheezing, and recurrent wheezing with an event with daycare attendance, number of siblings, respiratory infections, maternal smoking, and history of parental asthma. Logistic regression adjusting for the latter variables showed that recurrent wheezing (odds ratio, 0.4; 95% CI, 0.1-0.9) as well as 2 other wheeze outcomes were significantly reduced in homes with high endotoxin exposure in the presence of 2 or more dogs. Conclusion: Pet ownership or endotoxin did not independently modify aeroallergen sensitization or wheezing during infancy. However, high endotoxin exposure in the presence of multiple dogs was associated with reduced wheezing in infants. Clinical implications: A home environment with many dogs and high levels of endotoxin may be conducive to reduced wheezing in infancy.. endotoxin| birth cohort| wheeze| house dust| pet ownership|house-dust endotoxin| hay-fever| allergic sensitization| written questionnaire| decreased prevalence| asthmatic-children| respiratory health| childhood isaac| tobacco-smoke| birth cohort.	DEC-2006	endotoxin| birth cohort| wheeze| house dust| pet ownership|house-dust endotoxin| hay-fever| allergic sensitization| written questionnaire| decreased prevalence| asthmatic-children| respiratory health| childhood isaac| tobacco-smoke| birth cohort	Campo, P; Kalra, HK; Levin, L; Reponen, T; Olds, R; Lummus, ZL; Cho, SH; Hershey, GKK; Lockey, J; Villareal, M; Stanforth, S; LeMasters, G; Bernstein, DI	Influence of dog ownership and high endotoxin on wheezing and atopy during infancy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	endotoxin; birth cohort; wheeze; house dust; pet ownership	HOUSE-DUST ENDOTOXIN; HAY-FEVER; ALLERGIC SENSITIZATION; WRITTEN QUESTIONNAIRE; DECREASED PREVALENCE; ASTHMATIC-CHILDREN; RESPIRATORY HEALTH; CHILDHOOD ISAAC; TOBACCO-SMOKE; BIRTH COHORT	Background: Increased exposure to microbial products early in life may protect from development of atopic disorders in childhood. Few studies have examined the relationship of endotoxin exposure and pet ownership on atopy and wheezing during infancy. Objective: Evaluate relationships among high endotoxin exposure, pet ownership, atopy, and wheezing in high-risk infants. Methods: Infants (n = 532; mean age, 12.5 +/- 0.8 months) with at least 1 parent with confirmed atopy were recruited. A complete medical history and skin prick testing to foods and aeroallergens were performed at age 1 year. House dust samples were analyzed for endotoxin. Results: Prevalences of wheezing were not independently associated with dog or cat ownership or endotoxin levels. Percutaneous reactivity to at least 1 allergen was observed in 28.6% of infants. Univariate analyses showed significant associations of any wheezing, recurrent wheezing, and recurrent wheezing with an event with daycare attendance, number of siblings, respiratory infections, maternal smoking, and history of parental asthma. Logistic regression adjusting for the latter variables showed that recurrent wheezing (odds ratio, 0.4; 95% CI, 0.1-0.9) as well as 2 other wheeze outcomes were significantly reduced in homes with high endotoxin exposure in the presence of 2 or more dogs. Conclusion: Pet ownership or endotoxin did not independently modify aeroallergen sensitization or wheezing during infancy. However, high endotoxin exposure in the presence of multiple dogs was associated with reduced wheezing in infants. Clinical implications: A home environment with many dogs and high levels of endotoxin may be conducive to reduced wheezing in infancy.	50	74	2006	8	10.1016/j.jaci.2006.08.008	Allergy; Immunology
An overview of the association between allergy and cancer. Numerous epidemiological studies have evaluated some aspect of the association between a history of allergy and cancer occurrence. In this article, an overview of the epidemiological evidence is presented with a discussion of a number of methodological issues important in this area of study. Literature searches were conducted using the MEDLINE database from 1966 through to August 2005 to identify articles that explored a personal history of allergic disorders as a risk factor for cancer. Although it is difficult to draw conclusions between allergy and cancer at many sites because of insufficient evidence or a lack of consistency both within and among studies completed to date, strong inverse associations have been reported for pancreatic cancer and glioma, whereas lung cancer was positively associated with asthma. Additional studies are needed to confirm these finding and to address the limitations of previous studies, including the validity and reliability of exposure measures and control for confounding. Further, large prospective studies using cancer incidence would be particularly useful, including studies using biological markers of allergic status to reduce potential misclassification and to confirm the results of previous studies based on self-report. There is also a need for further basic research to clarify a potential mechanism, should an association exist. (c) 2006 Wiley-Liss, Inc.. non-hodgkins-lymphoma| acute lymphoblastic-leukemia| francisco bay area| chronic antigenic-stimulation| chronic lymphocytic-leukemia| population-based cohort| previous lung-disease| killer-cell-activity| prior medication use| adult brain-tumor.	JUN 15-2006	non-hodgkins-lymphoma| acute lymphoblastic-leukemia| francisco bay area| chronic antigenic-stimulation| chronic lymphocytic-leukemia| population-based cohort| previous lung-disease| killer-cell-activity| prior medication use| adult brain-tumor	Turner, MC; Chen, Y; Krewski, D; Ghadirian, P	An overview of the association between allergy and cancer		INTERNATIONAL JOURNAL OF CANCER		NON-HODGKINS-LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; FRANCISCO BAY AREA; CHRONIC ANTIGENIC-STIMULATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; POPULATION-BASED COHORT; PREVIOUS LUNG-DISEASE; KILLER-CELL-ACTIVITY; PRIOR MEDICATION USE; ADULT BRAIN-TUMOR	Numerous epidemiological studies have evaluated some aspect of the association between a history of allergy and cancer occurrence. In this article, an overview of the epidemiological evidence is presented with a discussion of a number of methodological issues important in this area of study. Literature searches were conducted using the MEDLINE database from 1966 through to August 2005 to identify articles that explored a personal history of allergic disorders as a risk factor for cancer. Although it is difficult to draw conclusions between allergy and cancer at many sites because of insufficient evidence or a lack of consistency both within and among studies completed to date, strong inverse associations have been reported for pancreatic cancer and glioma, whereas lung cancer was positively associated with asthma. Additional studies are needed to confirm these finding and to address the limitations of previous studies, including the validity and reliability of exposure measures and control for confounding. Further, large prospective studies using cancer incidence would be particularly useful, including studies using biological markers of allergic status to reduce potential misclassification and to confirm the results of previous studies based on self-report. There is also a need for further basic research to clarify a potential mechanism, should an association exist. (c) 2006 Wiley-Liss, Inc.	205	74	2006	9	10.1002/ijc.21752	Oncology
The H1 histamine receptor regulates allergic lung responses. Histamine, signaling via the type 1 receptor (H1R), has been shown to suppress Th2 cytokine production by in vitro cultured T cells. We examined the role of H1R in allergic inflammation in vivo using a murine asthma model. Allergen-stimulated splenic T cells from sensitized H1R(-/-) mice exhibited enhanced Th2 cytokine production. Despite this Th2 bias, allergen-challenged H1R(-/-) mice exhibited diminished lung Th2 cytokine mRNA levels, airway inflammation, goblet cell metaplasia, and airway hyperresponsiveness (AHR). Restoration of pulmonary Th2 cytokines in H1R(-/-) mice by intranasal IL-4 or IL-13 restored inflammatory lung responses and AHR Further investigation revealed that histamine acts as a T cell chemotactic factor and defective T cell trafficking was responsible for the absence of lung inflammation. Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R In vivo, allergen-specific WT but not H1R(-/-) CD4(+) T cells were recruited to the lungs of naive recipients following inhaled allergen challenge. H1R(-/-) cells failed to confer airway inflammation or AHR observed after transfer of WT T cells. Our data establish a role for histamine and H1R in promoting the migration of Th2 cells into sites of allergen exposure.. induced airway inflammation| t-cell| interferon-gamma| bronchial hyperresponsiveness| bronchoalveolar lavage| eosinophil chemotaxis| cytokine production| antigen receptor| epithelial-cells| dendritic cells.	JUN-2006	induced airway inflammation| t-cell| interferon-gamma| bronchial hyperresponsiveness| bronchoalveolar lavage| eosinophil chemotaxis| cytokine production| antigen receptor| epithelial-cells| dendritic cells	Bryce, PJ; Mathias, CB; Harrison, KL; Watanabe, T; Geha, RS; Oettgen, HC	The H1 histamine receptor regulates allergic lung responses		JOURNAL OF CLINICAL INVESTIGATION		INDUCED AIRWAY INFLAMMATION; T-CELL; INTERFERON-GAMMA; BRONCHIAL HYPERRESPONSIVENESS; BRONCHOALVEOLAR LAVAGE; EOSINOPHIL CHEMOTAXIS; CYTOKINE PRODUCTION; ANTIGEN RECEPTOR; EPITHELIAL-CELLS; DENDRITIC CELLS	Histamine, signaling via the type 1 receptor (H1R), has been shown to suppress Th2 cytokine production by in vitro cultured T cells. We examined the role of H1R in allergic inflammation in vivo using a murine asthma model. Allergen-stimulated splenic T cells from sensitized H1R(-/-) mice exhibited enhanced Th2 cytokine production. Despite this Th2 bias, allergen-challenged H1R(-/-) mice exhibited diminished lung Th2 cytokine mRNA levels, airway inflammation, goblet cell metaplasia, and airway hyperresponsiveness (AHR). Restoration of pulmonary Th2 cytokines in H1R(-/-) mice by intranasal IL-4 or IL-13 restored inflammatory lung responses and AHR Further investigation revealed that histamine acts as a T cell chemotactic factor and defective T cell trafficking was responsible for the absence of lung inflammation. Cultured T cells migrated in response to histamine in vitro, but this was ablated by blockade of H1R but not H2R In vivo, allergen-specific WT but not H1R(-/-) CD4(+) T cells were recruited to the lungs of naive recipients following inhaled allergen challenge. H1R(-/-) cells failed to confer airway inflammation or AHR observed after transfer of WT T cells. Our data establish a role for histamine and H1R in promoting the migration of Th2 cells into sites of allergen exposure.	57	74	2006	9	10.1172/JCI26150	Research & Experimental Medicine
Current asthma and respiratory symptoms among pupils in relation to dietary factors and allergens in the school environment. The aim was to study asthma and allergy in relation to diet and the school environment. Pupils (5-14 years) in eight schools received a questionnaire, 1014 participated (68%). Settled dust was collected on ALK-filters and analyzed for allergens from cat (Fel d 1), dog (Can f 1), horse (Equ cx), house dust mites (Der p 1, Der f 1), and cockroach (Bla g 1) by ELISA. In total, 6.8% reported cat allergy, 4.8% dog allergy, 7.7% doctor's diagnosed asthma and 5.9% current asthma, and 7.8% reported wheeze. Current asthma was less common among those consuming more fresh milk (P < 0.05) and fish (P < 0.01). Poly-unsaturated fatty acids was associated with more wheeze (P < 0.05), olive oil was associated with less doctors' diagnosed asthma (P < 0.05). Totally, 74% of the classrooms had mean CO2 < 1000 ppm. The median concentration per gram dust was 860 ng/g Fel d 1, 750 ng/g Can f 1 and 954 U/g Equ cx. Horse allergen was associated with more wheeze (P < 0.05), daytime breathlessness (P < 0.05), current asthma (P < 0.05) and atopic sensitization (P < 0.05). Dog allergen was associated with wheeze (P < 0.05) and daytime breathlessness (P < 0.05). The associations between allergens and respiratory symptoms were more pronounced among those consuming margarine, not consuming butter, and with a low intake of milk. In conclusion, cat, dog and horse allergens in schools could be a risk factor for asthma and atopic sensitization, and dietary factors may interact with the allergen exposure.. asthma| cat allergen (fel d 1)| dietary factors| dog allergen (can f 1)| horse allergen (equ cx)| school environment|childhood asthma| cat allergen| swedish schoolchildren| atopic sensitization| fish consumption| health-survey| young-adults| risk-factors| air-quality| new-zealand.	JUN-2005	asthma| cat allergen (fel d 1)| dietary factors| dog allergen (can f 1)| horse allergen (equ cx)| school environment|childhood asthma| cat allergen| swedish schoolchildren| atopic sensitization| fish consumption| health-survey| young-adults| risk-factors| air-quality| new-zealand	Kim, JL; Elfman, L; Mi, Y; Johansson, M; Smedje, G; Norback, D	Current asthma and respiratory symptoms among pupils in relation to dietary factors and allergens in the school environment		INDOOR AIR	asthma; cat allergen (Fel d 1); dietary factors; dog allergen (Can f 1); horse allergen (Equ cx); school environment	CHILDHOOD ASTHMA; CAT ALLERGEN; SWEDISH SCHOOLCHILDREN; ATOPIC SENSITIZATION; FISH CONSUMPTION; HEALTH-SURVEY; YOUNG-ADULTS; RISK-FACTORS; AIR-QUALITY; NEW-ZEALAND	The aim was to study asthma and allergy in relation to diet and the school environment. Pupils (5-14 years) in eight schools received a questionnaire, 1014 participated (68%). Settled dust was collected on ALK-filters and analyzed for allergens from cat (Fel d 1), dog (Can f 1), horse (Equ cx), house dust mites (Der p 1, Der f 1), and cockroach (Bla g 1) by ELISA. In total, 6.8% reported cat allergy, 4.8% dog allergy, 7.7% doctor's diagnosed asthma and 5.9% current asthma, and 7.8% reported wheeze. Current asthma was less common among those consuming more fresh milk (P < 0.05) and fish (P < 0.01). Poly-unsaturated fatty acids was associated with more wheeze (P < 0.05), olive oil was associated with less doctors' diagnosed asthma (P < 0.05). Totally, 74% of the classrooms had mean CO2 < 1000 ppm. The median concentration per gram dust was 860 ng/g Fel d 1, 750 ng/g Can f 1 and 954 U/g Equ cx. Horse allergen was associated with more wheeze (P < 0.05), daytime breathlessness (P < 0.05), current asthma (P < 0.05) and atopic sensitization (P < 0.05). Dog allergen was associated with wheeze (P < 0.05) and daytime breathlessness (P < 0.05). The associations between allergens and respiratory symptoms were more pronounced among those consuming margarine, not consuming butter, and with a low intake of milk. In conclusion, cat, dog and horse allergens in schools could be a risk factor for asthma and atopic sensitization, and dietary factors may interact with the allergen exposure.	61	74	2005	13	10.1111/j.1600-0668.2005.00334.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
The critical role of hematopoietic cells in lipopolysaccharide-induced airway inflammation. Rapid and selective recruitment of neutrophils into the airspace in response to LPS facilitates the clearance of bacterial pathogens. However, neutrophil infiltration can also participate in the development and progression of environmental airway disease. Previous data have revealed that Toll-like receptor 4 (tlr4) is required for neutrophil recruitment to the lung after either inhaled or systemically administrated LPS from Escherichia coli. Although many cell types express tlr4, endothelial cell expression of tlr4 is specifically required to sequester neutrophils in the lung in response to systemic endotoxin. To identify the cell types requiring trl4 expression for neutrophil recruitment after inhaled LPS, we generated chimeric mice separately expressing tlr4 on either hematopoietic cells or on structural lung cells. Neutrophil recruitment into the airspace was completely restored in tlr4-deficient mice receiving wild-type bone marrow. By contrast, wild-type animals receiving tlr4-deficient marrow had dramatically reduced neutrophil recruitment. Moreover, adoptive transfer of wild-type alveolar macrophages also restored the ability of tlr4-deficient recipient mice to recruit neutrophils to the lung. These data demonstrate the critical role of hematopoietic cells and alveolar macrophages in initiating LPS-induced neutrophil recruitment from the vascular space to the airspace.. innate immunity| lipopolysaccharide| macrophage| neutrophil| toll-like receptor|toll-like receptor-4| acute lung injury| neutrophil recruitment| bronchial reactivity| endotoxin exposure| inhaled endotoxin| epithelial-cells| mice| asthma| tlr4.	APR 15-2005	innate immunity| lipopolysaccharide| macrophage| neutrophil| toll-like receptor|toll-like receptor-4| acute lung injury| neutrophil recruitment| bronchial reactivity| endotoxin exposure| inhaled endotoxin| epithelial-cells| mice| asthma| tlr4	Hollingsworth, JW; Chen, BJ; Brass, DM; Berman, K; Gunn, MD; Cook, DN; Schwartz, DA	The critical role of hematopoietic cells in lipopolysaccharide-induced airway inflammation		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	innate immunity; lipopolysaccharide; macrophage; neutrophil; toll-like receptor	TOLL-LIKE RECEPTOR-4; ACUTE LUNG INJURY; NEUTROPHIL RECRUITMENT; BRONCHIAL REACTIVITY; ENDOTOXIN EXPOSURE; INHALED ENDOTOXIN; EPITHELIAL-CELLS; MICE; ASTHMA; TLR4	Rapid and selective recruitment of neutrophils into the airspace in response to LPS facilitates the clearance of bacterial pathogens. However, neutrophil infiltration can also participate in the development and progression of environmental airway disease. Previous data have revealed that Toll-like receptor 4 (tlr4) is required for neutrophil recruitment to the lung after either inhaled or systemically administrated LPS from Escherichia coli. Although many cell types express tlr4, endothelial cell expression of tlr4 is specifically required to sequester neutrophils in the lung in response to systemic endotoxin. To identify the cell types requiring trl4 expression for neutrophil recruitment after inhaled LPS, we generated chimeric mice separately expressing tlr4 on either hematopoietic cells or on structural lung cells. Neutrophil recruitment into the airspace was completely restored in tlr4-deficient mice receiving wild-type bone marrow. By contrast, wild-type animals receiving tlr4-deficient marrow had dramatically reduced neutrophil recruitment. Moreover, adoptive transfer of wild-type alveolar macrophages also restored the ability of tlr4-deficient recipient mice to recruit neutrophils to the lung. These data demonstrate the critical role of hematopoietic cells and alveolar macrophages in initiating LPS-induced neutrophil recruitment from the vascular space to the airspace.	50	74	2005	8	10.1164/rccm.200407.953OC	General & Internal Medicine; Respiratory System
Gene-environment interactions in asthma and other respiratory diseases. It is generally agreed that many lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) have polygenic inheritance, and that the association of a specific genotype or genotypes with the disease is likely to vary between populations. Furthermore, it is recognized that the etiology of many lung diseases involves a complex interplay between genetic background and exposure to multiple environmental stimuli, and understanding the mechanisms through which genes and environment interact represents a major challenge for pulmonary researchers. We discuss experimental approaches and challenges that must be overcome to identify disease genes for asthma, COPD and chronic bronchitis, and occupational lung diseases. In particular, common polymorphisms in CD14, glutathione S-transferase, and tumor necrosis factor alpha have been found to be important in gene-environment interaction and asthma pathogenesis. An understanding of gene-environment interactions in complex lung diseases is essential to the development of new strategies for lung disease prevention and treatment.. pollutant| allergen| polymorphism| linkage analysis|obstructive pulmonary-disease| necrosis-factor-alpha| s-transferase m1| chronic beryllium disease| diesel exhaust particles| class-ii alleles| childhood lung-function| house-dust endotoxin| linkage analysis| air-pollution.	2005	pollutant| allergen| polymorphism| linkage analysis|obstructive pulmonary-disease| necrosis-factor-alpha| s-transferase m1| chronic beryllium disease| diesel exhaust particles| class-ii alleles| childhood lung-function| house-dust endotoxin| linkage analysis| air-pollution	Kleeberger, SR; Peden, D	Gene-environment interactions in asthma and other respiratory diseases		ANNUAL REVIEW OF MEDICINE	pollutant; allergen; polymorphism; linkage analysis	OBSTRUCTIVE PULMONARY-DISEASE; NECROSIS-FACTOR-ALPHA; S-TRANSFERASE M1; CHRONIC BERYLLIUM DISEASE; DIESEL EXHAUST PARTICLES; CLASS-II ALLELES; CHILDHOOD LUNG-FUNCTION; HOUSE-DUST ENDOTOXIN; LINKAGE ANALYSIS; AIR-POLLUTION	It is generally agreed that many lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) have polygenic inheritance, and that the association of a specific genotype or genotypes with the disease is likely to vary between populations. Furthermore, it is recognized that the etiology of many lung diseases involves a complex interplay between genetic background and exposure to multiple environmental stimuli, and understanding the mechanisms through which genes and environment interact represents a major challenge for pulmonary researchers. We discuss experimental approaches and challenges that must be overcome to identify disease genes for asthma, COPD and chronic bronchitis, and occupational lung diseases. In particular, common polymorphisms in CD14, glutathione S-transferase, and tumor necrosis factor alpha have been found to be important in gene-environment interaction and asthma pathogenesis. An understanding of gene-environment interactions in complex lung diseases is essential to the development of new strategies for lung disease prevention and treatment.	107	74	2005	18	10.1146/annurev/med.56.062904.144908	General & Internal Medicine
Self-reported prevalence and risk factors of asthma among Korean adolescents: 5-year follow-up study, 1995-2000. Objectives The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires have shown that the prevalence of childhood asthma is increasing worldwide. Although Asian countries used to have lower prevalence rates of allergic disease than Western countries, this prevalence is increasing in several Asian countries. To determine whether the prevalence of childhood asthma is changing in Korean adolescents, we compared findings from nationwide cross-sectional surveys in 1995 and 2000 on populations of middle-school children using the Korean version of the ISAAC questionnaire. Methods We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 15 481 children, ages 12-15, and encompassing all three grades in middle school, selected from 34 schools across the nation; the response rate was 97.3%. In 2000, 15 894 children were selected from 31 of the same schools, and the response rate was 96.4%. The SAS system version 8.0 was utilized for all statistical analyses. Results The WQ showed that the lifetime and 12-month prevalence of wheeze did not change from 1995 to 2000. While the 12-month prevalence rates of sleep disturbed by wheezing and night cough increased, the rates of severe attack of wheezing and exercise-induced wheeze did not change, over this period of time. The lifetime prevalence of asthma diagnosis, however, increased significantly, from 2.7% in 1995 to 5.3% in 2000, as did the 12-month prevalence of asthma treatment, from 1.0% in 1995 to 1.9% in 2000. The AVQ also showed increases in the lifetime and 12-month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time. These were especially because of significant increases in the Provincial cities of Korea. Interestingly, the 12-month prevalence of wheeze was consistently high in Cheju with low air pollution indices, whereas this rate was low in Ulsan and Ansan with very high air pollution indices. Risk factor analysis showed that body mass index (BMI), passive smoking, and living with a dog or cat, but not air pollution, were associated with higher risk of wheeze. Conclusions In the 5-year period from 1995 to 2000, the prevalence of asthma symptoms has increased in Korean adolescents, much of it because of increases in Provincial Centers. BMI, passive smoking, and living with a dog or cat are important risk factors. Environmental factors other than air pollution may be associated with increases in asthma, especially in Provincial Centers.. adolescent| asthma| middle-school children| prevalence| risk factor|body-mass index| childhood asthma| children| symptoms| trends| isaac| hospitalization| questionnaire| association| smoking.	OCT-2004	adolescent| asthma| middle-school children| prevalence| risk factor|body-mass index| childhood asthma| children| symptoms| trends| isaac| hospitalization| questionnaire| association| smoking	Hong, SJ; Lee, MS; Sohn, MH; Shim, JY; Han, YS; Park, KS; Ahn, YM; Son, BK; Lee, HB	Self-reported prevalence and risk factors of asthma among Korean adolescents: 5-year follow-up study, 1995-2000		CLINICAL AND EXPERIMENTAL ALLERGY	adolescent; asthma; middle-school children; prevalence; risk factor	BODY-MASS INDEX; CHILDHOOD ASTHMA; CHILDREN; SYMPTOMS; TRENDS; ISAAC; HOSPITALIZATION; QUESTIONNAIRE; ASSOCIATION; SMOKING	Objectives The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires have shown that the prevalence of childhood asthma is increasing worldwide. Although Asian countries used to have lower prevalence rates of allergic disease than Western countries, this prevalence is increasing in several Asian countries. To determine whether the prevalence of childhood asthma is changing in Korean adolescents, we compared findings from nationwide cross-sectional surveys in 1995 and 2000 on populations of middle-school children using the Korean version of the ISAAC questionnaire. Methods We developed Korean versions of the ISAAC written (WQ) and video (AVQ) questionnaires for allergic diseases. In 1995, the enrolled population consisted of 15 481 children, ages 12-15, and encompassing all three grades in middle school, selected from 34 schools across the nation; the response rate was 97.3%. In 2000, 15 894 children were selected from 31 of the same schools, and the response rate was 96.4%. The SAS system version 8.0 was utilized for all statistical analyses. Results The WQ showed that the lifetime and 12-month prevalence of wheeze did not change from 1995 to 2000. While the 12-month prevalence rates of sleep disturbed by wheezing and night cough increased, the rates of severe attack of wheezing and exercise-induced wheeze did not change, over this period of time. The lifetime prevalence of asthma diagnosis, however, increased significantly, from 2.7% in 1995 to 5.3% in 2000, as did the 12-month prevalence of asthma treatment, from 1.0% in 1995 to 1.9% in 2000. The AVQ also showed increases in the lifetime and 12-month prevalence rates of wheeze at rest, exercise-induced wheeze, nocturnal wheeze, nocturnal cough, and severe wheeze over this period of time. These were especially because of significant increases in the Provincial cities of Korea. Interestingly, the 12-month prevalence of wheeze was consistently high in Cheju with low air pollution indices, whereas this rate was low in Ulsan and Ansan with very high air pollution indices. Risk factor analysis showed that body mass index (BMI), passive smoking, and living with a dog or cat, but not air pollution, were associated with higher risk of wheeze. Conclusions In the 5-year period from 1995 to 2000, the prevalence of asthma symptoms has increased in Korean adolescents, much of it because of increases in Provincial Centers. BMI, passive smoking, and living with a dog or cat are important risk factors. Environmental factors other than air pollution may be associated with increases in asthma, especially in Provincial Centers.	33	74	2004	7	10.1111/j.1365-2222.2004.02084.x	Allergy; Immunology
Frequency of contact allergy in German children and adolescents patch tested between 1995 and 2002: results from the Information Network of Departments of Dermatology and the German Contact Dermatitis Research Group. Allergic contact dermatitis (ACD) affects approximately 7% of the general population. To evaluate the frequency of ACD in children, we analysed patch test results collected by the Information Network of Departments of Dermatology between 1995 and 2002. Data of 285 children (6-12 year) and 2175 adolescent patients (13-18 year) were analysed to determine the frequency of sensitization to the 30 most common contact allergens, adjusting for age and sex. As control group, we defined adult patients (60-66 year, n = 7904). The top allergens in children were thimerosal, gentamicin sulphate, nickel-II-sulphate, ammoniated mercury, cobalt-II-chloride, fragrance mix, bufexamac, Compositae mix, propylene glycol and turpentine. The overall proportion of sensitized patients according to the patch test results was 52.6% in the children group compared to 49.7% in the adolescent group. These findings were similar in the adult group at 52.2%. The detailed analysis regarding sex, occupation, atopy, site of eczema and age showed distinct patterns in each group indicating age-specific exposures. Atopy-related diseases were more common in children compared to adults. On the basis of the data of this study, the relationship between atopy and the risk of development of ACD, at least in children, needs further investigation.. allergic contact dermatitis| children| clinical epidemiology| contact allergy| patch testing|sensitization| thimerosal| ivdk| epidemiology| adults| dkg| sex| age.	SEP-2004	allergic contact dermatitis| children| clinical epidemiology| contact allergy| patch testing|sensitization| thimerosal| ivdk| epidemiology| adults| dkg| sex| age	Heine, G; Schnuch, A; Uter, W; Worm, M	Frequency of contact allergy in German children and adolescents patch tested between 1995 and 2002: results from the Information Network of Departments of Dermatology and the German Contact Dermatitis Research Group		CONTACT DERMATITIS	allergic contact dermatitis; children; clinical epidemiology; contact allergy; patch testing	SENSITIZATION; THIMEROSAL; IVDK; EPIDEMIOLOGY; ADULTS; DKG; SEX; AGE	Allergic contact dermatitis (ACD) affects approximately 7% of the general population. To evaluate the frequency of ACD in children, we analysed patch test results collected by the Information Network of Departments of Dermatology between 1995 and 2002. Data of 285 children (6-12 year) and 2175 adolescent patients (13-18 year) were analysed to determine the frequency of sensitization to the 30 most common contact allergens, adjusting for age and sex. As control group, we defined adult patients (60-66 year, n = 7904). The top allergens in children were thimerosal, gentamicin sulphate, nickel-II-sulphate, ammoniated mercury, cobalt-II-chloride, fragrance mix, bufexamac, Compositae mix, propylene glycol and turpentine. The overall proportion of sensitized patients according to the patch test results was 52.6% in the children group compared to 49.7% in the adolescent group. These findings were similar in the adult group at 52.2%. The detailed analysis regarding sex, occupation, atopy, site of eczema and age showed distinct patterns in each group indicating age-specific exposures. Atopy-related diseases were more common in children compared to adults. On the basis of the data of this study, the relationship between atopy and the risk of development of ACD, at least in children, needs further investigation.	29	74	2004	7	10.1111/j.0105-1873.2004.00411.x	Allergy; Dermatology
Air-borne viable, non-viable, and allergenic fungi in a rural agricultural area of India: a 2-year study at five outdoor sampling stations. The information on airborne allergenic fungal flora in rural agricultural areas is largely lacking. Adequate information is not available to the bioaerosol researchers regarding the choice of single versus multiple sampling stations for the monitoring of both viable and non-viable airborne fungi. There is no long-term study estimating the ratios of viable and non-viable fungi in the air and earlier studies did not focus on the fractions of airborne allergenic fungi with respect to the total airborne fungal load. To fill these knowledge gaps, volumetric paired assessments of airborne viable and non-viable fungi were performed in five outdoor sampling stations during two consecutive years in a rural agricultural area of India. Samples were collected at 10-day intervals by the Burkard Personal Slide Sampler and the Andersen Two-Stage Viable Sampler. The data on the concentrations of total and individual fungal types from five stations and 2 different years were analyzed and compared by statistical methods. The allergenicity of the prevalent airborne viable fungi was estimated by the skin-prick tests of > 100 rural allergy patients using the antigenic fungal extracts from isolates collected with the Andersen sampler. The ranges of total fungal spore concentration were 82-2365 spores per cubic meter of air (spores/m(3)) in the first sampling year and 156-2022 spores/m(3) in the second sampling year. The concentration ranges of viable fungi were 72-1796 colony-forming units per cubic meter of air (CFU/m(3)) in the first sampling year and 155-1256 CFU/m(3) in the second sampling year. No statistically significant difference was observed between the total spore data of the 2 years, however, the data between five stations showed a significant difference (P<0.0001). No statistically significant difference existed between stations and years with respect to the concentration of viable fungi. When the data of individual allergenic fungal concentrations were compared between stations and years, no statistically significant difference was observed in all cases except for Aspergillus japonicus and Rhizopus nigricans, which showed significant difference in case of stations and years, respectively. The ratios between the total fungal spores collected by the Burkard sampler and the viable fungi collected by the Andersen sampler from all sampling stations ranged between 0.29 and 7.61. The antigenic extracts of eight prevalent viable airborne fungi (A. flavus, A. japonicus, A. fumigatus, Alternaria alternata, Cladosporium cladosporioides, Curvularia pallescens, Fusarium roseum, and R. nigricans) demonstrated > 60% positive reactions in the skin prick test. These selected allergenic fungi collectively represented 31.7-63.2% of the total airborne viable fungi in different stations. The study concluded that: (i) a rich fungal airspora existed in the rural study area, (ii) to achieve representative information on the total airborne fungal spores of an area, the monitoring in multiple sampling stations is preferable over a single sampling station; for viable fungi, however, one station can be considered, (iii) the percentage of airborne fungal viability is higher in rural agricultural areas, and (iv) approximately 52% of the viable airborne fungi in the rural study area were allergenic. (C) 2003 Elsevier B.V. All rights reserved.. airborne fungi| bioaerosol| allergy| rural area| aerobiology| air microbiology|different sites| airborne| spores| symptoms| asthma| microorganisms| environments| enumeration| dusts.	JUN 29-2004	airborne fungi| bioaerosol| allergy| rural area| aerobiology| air microbiology|different sites| airborne| spores| symptoms| asthma| microorganisms| environments| enumeration| dusts	Adhikari, A; Sen, MM; Gupta-Bhattacharya, S; Chanda, S	Air-borne viable, non-viable, and allergenic fungi in a rural agricultural area of India: a 2-year study at five outdoor sampling stations		SCIENCE OF THE TOTAL ENVIRONMENT	airborne fungi; bioaerosol; allergy; rural area; aerobiology; air microbiology	DIFFERENT SITES; AIRBORNE; SPORES; SYMPTOMS; ASTHMA; MICROORGANISMS; ENVIRONMENTS; ENUMERATION; DUSTS	The information on airborne allergenic fungal flora in rural agricultural areas is largely lacking. Adequate information is not available to the bioaerosol researchers regarding the choice of single versus multiple sampling stations for the monitoring of both viable and non-viable airborne fungi. There is no long-term study estimating the ratios of viable and non-viable fungi in the air and earlier studies did not focus on the fractions of airborne allergenic fungi with respect to the total airborne fungal load. To fill these knowledge gaps, volumetric paired assessments of airborne viable and non-viable fungi were performed in five outdoor sampling stations during two consecutive years in a rural agricultural area of India. Samples were collected at 10-day intervals by the Burkard Personal Slide Sampler and the Andersen Two-Stage Viable Sampler. The data on the concentrations of total and individual fungal types from five stations and 2 different years were analyzed and compared by statistical methods. The allergenicity of the prevalent airborne viable fungi was estimated by the skin-prick tests of > 100 rural allergy patients using the antigenic fungal extracts from isolates collected with the Andersen sampler. The ranges of total fungal spore concentration were 82-2365 spores per cubic meter of air (spores/m(3)) in the first sampling year and 156-2022 spores/m(3) in the second sampling year. The concentration ranges of viable fungi were 72-1796 colony-forming units per cubic meter of air (CFU/m(3)) in the first sampling year and 155-1256 CFU/m(3) in the second sampling year. No statistically significant difference was observed between the total spore data of the 2 years, however, the data between five stations showed a significant difference (P<0.0001). No statistically significant difference existed between stations and years with respect to the concentration of viable fungi. When the data of individual allergenic fungal concentrations were compared between stations and years, no statistically significant difference was observed in all cases except for Aspergillus japonicus and Rhizopus nigricans, which showed significant difference in case of stations and years, respectively. The ratios between the total fungal spores collected by the Burkard sampler and the viable fungi collected by the Andersen sampler from all sampling stations ranged between 0.29 and 7.61. The antigenic extracts of eight prevalent viable airborne fungi (A. flavus, A. japonicus, A. fumigatus, Alternaria alternata, Cladosporium cladosporioides, Curvularia pallescens, Fusarium roseum, and R. nigricans) demonstrated > 60% positive reactions in the skin prick test. These selected allergenic fungi collectively represented 31.7-63.2% of the total airborne viable fungi in different stations. The study concluded that: (i) a rich fungal airspora existed in the rural study area, (ii) to achieve representative information on the total airborne fungal spores of an area, the monitoring in multiple sampling stations is preferable over a single sampling station; for viable fungi, however, one station can be considered, (iii) the percentage of airborne fungal viability is higher in rural agricultural areas, and (iv) approximately 52% of the viable airborne fungi in the rural study area were allergenic. (C) 2003 Elsevier B.V. All rights reserved.	44	74	2004	19	10.1016/j.scitotenv.2003.12.007	Environmental Sciences & Ecology
Mast cells, Fc epsilon RI, and IL-13 are required for development of airway hyperresponsiveness after aerosolized allergen exposure in the absence of adjuvant. In certain models of allergic airway disease, mast cells facilitate the development of inflammation and airway hyper-responsiveness (AHR). To define the role of the high affinity IgE receptor (Fcis an element ofRI) in the development of AHR, mice with a disruption of the a subunit of the high affinity IgE receptor (Fcis an element ofRI(-/-)) were exposed on 10 consecutive days to nebulized OVA. Forty-eight hours after the last nebulization, airway responsiveness was monitored by the contractile response of tracheal smooth muscle to electrical field. stimulation (EFS). After the 10-day OVA challenge protocol, wild-type mice demonstrated increased responsiveness to EFS, whereas similarly challenged Fcis an element ofRI(-/-) mice showed a low response to EFS, similar to nonexposed animals. Further, allergen-challenged Fcis an element ofRI(-/-) mice showed less airway inflammation, goblet cell hyperplasia, and lower levels of IL-13 in lung homogenates compared with the controls. IL-13-deficient mice failed to develop an increased response to EFS or goblet cell hyperplasia after the 10-day OVA challenge. We transferred bone marrow-derived mast cells from wild-type mice to Fcis an element ofRI(-/-) mice 1 day before initiating the challenge protocol. After the 10-day OVA challenge, recipient Fcis an element ofRI(-/-) mice demonstrated EFS-induced responses similar to those of challenged wild-type mice. Transferred mast cells could be detected in tracheal preparations. These results show that Fcis an element ofRI is important for the development of AHR after an aerosolized allergen sensitization protocol and that this effect is mediated through Fcis an element ofRI on mast cells and production of IL-13 in the lung.. n-terminal kinase| c-kit ligand| deficient mice| pulmonary eosinophilia| bronchial responsiveness| cytokine production| phase-separation| ige production| triton x-114| asthma model.	MAY 15-2004	n-terminal kinase| c-kit ligand| deficient mice| pulmonary eosinophilia| bronchial responsiveness| cytokine production| phase-separation| ige production| triton x-114| asthma model	Taube, C; Wei, XD; Swasey, CH; Joetham, A; Zarini, S; Lively, T; Takeda, K; Loader, J; Miyahara, N; Kodama, T; Shultz, LD; Donaldson, DD; Hamelmann, EH; Dakhama, A; Gelfand, EW	Mast cells, Fc epsilon RI, and IL-13 are required for development of airway hyperresponsiveness after aerosolized allergen exposure in the absence of adjuvant		JOURNAL OF IMMUNOLOGY		N-TERMINAL KINASE; C-KIT LIGAND; DEFICIENT MICE; PULMONARY EOSINOPHILIA; BRONCHIAL RESPONSIVENESS; CYTOKINE PRODUCTION; PHASE-SEPARATION; IGE PRODUCTION; TRITON X-114; ASTHMA MODEL	In certain models of allergic airway disease, mast cells facilitate the development of inflammation and airway hyper-responsiveness (AHR). To define the role of the high affinity IgE receptor (Fcis an element ofRI) in the development of AHR, mice with a disruption of the a subunit of the high affinity IgE receptor (Fcis an element ofRI(-/-)) were exposed on 10 consecutive days to nebulized OVA. Forty-eight hours after the last nebulization, airway responsiveness was monitored by the contractile response of tracheal smooth muscle to electrical field. stimulation (EFS). After the 10-day OVA challenge protocol, wild-type mice demonstrated increased responsiveness to EFS, whereas similarly challenged Fcis an element ofRI(-/-) mice showed a low response to EFS, similar to nonexposed animals. Further, allergen-challenged Fcis an element ofRI(-/-) mice showed less airway inflammation, goblet cell hyperplasia, and lower levels of IL-13 in lung homogenates compared with the controls. IL-13-deficient mice failed to develop an increased response to EFS or goblet cell hyperplasia after the 10-day OVA challenge. We transferred bone marrow-derived mast cells from wild-type mice to Fcis an element ofRI(-/-) mice 1 day before initiating the challenge protocol. After the 10-day OVA challenge, recipient Fcis an element ofRI(-/-) mice demonstrated EFS-induced responses similar to those of challenged wild-type mice. Transferred mast cells could be detected in tracheal preparations. These results show that Fcis an element ofRI is important for the development of AHR after an aerosolized allergen sensitization protocol and that this effect is mediated through Fcis an element ofRI on mast cells and production of IL-13 in the lung.	61	74	2004	9		Immunology
N-3 polyunsaturated fatty acids and allergic disease. Purpose of review With escalating rates of allergic disease, it is vital to explore novel causal pathways. This review examines the evidence for a potential role of changing dietary intake of omega-3 polyunsaturated fatty acids in the development, treatment and prevention of allergic diseases. Recent findings Although it is difficult to determine the contribution of altered (decreased) dietary intake of omega-3 polyunsaturated fatty acids to the recent rise in the incidence of allergic disease, there is growing evidence that these nutrients have antiinflammatory properties and may modulate immune responses. These fatty acids have few side effects, and may be of some benefit in established allergic diseases (such as asthma and atopic dermatitis), although these effects are not strong. Because of this limited efficacy in established disease, the focus has shifted to the potential benefits of these immune modulators in earlier life for disease prevention. Two recent preliminary reports in infants suggest that dietary omega-3 polyunsaturated fatty acid supplements in pregnancy or in the early postnatal period could have immunomodulatory properties and associated clinical effects, although more studies are now needed. Novel synthetic polyunsaturated fatty acids with more potent and selective antiinflammatory effects may also provide safe therapeutic and preventive strategies in the future. Summary Dietary factors are important but still under-explored candidates in the search for environmental strategies to reduce the enormous impact of allergic diseases in modernized societies. There is an ongoing need for further research into the role of omega-3 polyunsaturated fatty acids in allergic disease, particularly in early life before atopy is established.. n-3 polyunsaturated fatty acids| fish oil| docosahexaenoic acid| arachidonic acid| allergic disease| atopy| eicosapentaenoic acid| asthma|tumor-necrosis-factor| house-dust mite| type-2 cytokine production| fish-oil supplementation| placebo-controlled trial| t-helper type-1| bronchial-asthma| dietary supplementation| atopic-dermatitis| childhood asthma.	MAR-2004	n-3 polyunsaturated fatty acids| fish oil| docosahexaenoic acid| arachidonic acid| allergic disease| atopy| eicosapentaenoic acid| asthma|tumor-necrosis-factor| house-dust mite| type-2 cytokine production| fish-oil supplementation| placebo-controlled trial| t-helper type-1| bronchial-asthma| dietary supplementation| atopic-dermatitis| childhood asthma	Prescott, SL; Calder, PC	N-3 polyunsaturated fatty acids and allergic disease		CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE	n-3 polyunsaturated fatty acids; fish oil; docosahexaenoic acid; arachidonic acid; allergic disease; atopy; eicosapentaenoic acid; asthma	TUMOR-NECROSIS-FACTOR; HOUSE-DUST MITE; TYPE-2 CYTOKINE PRODUCTION; FISH-OIL SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; T-HELPER TYPE-1; BRONCHIAL-ASTHMA; DIETARY SUPPLEMENTATION; ATOPIC-DERMATITIS; CHILDHOOD ASTHMA	Purpose of review With escalating rates of allergic disease, it is vital to explore novel causal pathways. This review examines the evidence for a potential role of changing dietary intake of omega-3 polyunsaturated fatty acids in the development, treatment and prevention of allergic diseases. Recent findings Although it is difficult to determine the contribution of altered (decreased) dietary intake of omega-3 polyunsaturated fatty acids to the recent rise in the incidence of allergic disease, there is growing evidence that these nutrients have antiinflammatory properties and may modulate immune responses. These fatty acids have few side effects, and may be of some benefit in established allergic diseases (such as asthma and atopic dermatitis), although these effects are not strong. Because of this limited efficacy in established disease, the focus has shifted to the potential benefits of these immune modulators in earlier life for disease prevention. Two recent preliminary reports in infants suggest that dietary omega-3 polyunsaturated fatty acid supplements in pregnancy or in the early postnatal period could have immunomodulatory properties and associated clinical effects, although more studies are now needed. Novel synthetic polyunsaturated fatty acids with more potent and selective antiinflammatory effects may also provide safe therapeutic and preventive strategies in the future. Summary Dietary factors are important but still under-explored candidates in the search for environmental strategies to reduce the enormous impact of allergic diseases in modernized societies. There is an ongoing need for further research into the role of omega-3 polyunsaturated fatty acids in allergic disease, particularly in early life before atopy is established.	76	74	2004	7	10.1097/00075197-200403000-00004	Endocrinology & Metabolism; Nutrition & Dietetics
Increasing prevalence of allergic rhinitis but not asthma among children in Hong Kong from 1995 to 2001 (Phase 3 International Study of Asthma and Allergies in Childhood). There is a worldwide belief that the prevalence of asthma and other allergic diseases is increasing but the measures used in many studies are susceptible to systematic errors. We examined the trend of asthma, allergic rhinitis and eczema prevalence in school children aged 6-7 years in Hong Kong from 1995 to 2001 using standardized ISAAC methodology. There were 4448 and 3618 children participating in 2001 and 1995, respectively. The prevalence of life-time rhinitis (42.4% vs. 38.9%, p < 0.01), current rhinitis (37.4% vs. 35.1%, p < 0.03), current rhinoconjunctivitis (17.2 vs. 13.6 %, p < 0.01) and life-time eczema (30.7% vs. 28.1%, p = 0.01) increased significantly. There was no significant change in prevalence of life-time asthma, life-time wheeze and current wheeze albeit a significant increase in severe asthma symptoms. We investigated a number of potential risk factors including sex, family history of atopy, sibship size, birth weight, respiratory tract infections, pet ownership and exposure to tobacco smoke. However, the increases in prevalence of rhinitis and eczema could not be entirely explained by the change of prevalence of these risk factors. The odds ratio OR for the study period remained significantly associated with current rhinitis (OR 1.31, 95% confidence intervals CI 1.17-1.46), current rhinoconjunctivitis (OR 1.63, 95% Cl 1.41-1.87) and life-time eczema (OR 1.30, 95% CI 1.16-1.45) after adjustment for these confounding variables using logistic regression model. Further study is warranted to elucidate the factors contributing to the observable change in the prevalence of rhinitis in our population.. trend prevalence| asthma| allergic rhinitis| eczema| children| hong kong|atopic eczema| worldwide variations| critical-appraisal| school-children| birth cohort| risk-factors| symptoms| sensitization| isaac| rhinoconjunctivitis.	FEB-2004	trend prevalence| asthma| allergic rhinitis| eczema| children| hong kong|atopic eczema| worldwide variations| critical-appraisal| school-children| birth cohort| risk-factors| symptoms| sensitization| isaac| rhinoconjunctivitis	Lee, SL; Wong, W; Lau, YL	Increasing prevalence of allergic rhinitis but not asthma among children in Hong Kong from 1995 to 2001 (Phase 3 International Study of Asthma and Allergies in Childhood)		PEDIATRIC ALLERGY AND IMMUNOLOGY	trend prevalence; asthma; allergic rhinitis; eczema; children; Hong Kong	ATOPIC ECZEMA; WORLDWIDE VARIATIONS; CRITICAL-APPRAISAL; SCHOOL-CHILDREN; BIRTH COHORT; RISK-FACTORS; SYMPTOMS; SENSITIZATION; ISAAC; RHINOCONJUNCTIVITIS	There is a worldwide belief that the prevalence of asthma and other allergic diseases is increasing but the measures used in many studies are susceptible to systematic errors. We examined the trend of asthma, allergic rhinitis and eczema prevalence in school children aged 6-7 years in Hong Kong from 1995 to 2001 using standardized ISAAC methodology. There were 4448 and 3618 children participating in 2001 and 1995, respectively. The prevalence of life-time rhinitis (42.4% vs. 38.9%, p < 0.01), current rhinitis (37.4% vs. 35.1%, p < 0.03), current rhinoconjunctivitis (17.2 vs. 13.6 %, p < 0.01) and life-time eczema (30.7% vs. 28.1%, p = 0.01) increased significantly. There was no significant change in prevalence of life-time asthma, life-time wheeze and current wheeze albeit a significant increase in severe asthma symptoms. We investigated a number of potential risk factors including sex, family history of atopy, sibship size, birth weight, respiratory tract infections, pet ownership and exposure to tobacco smoke. However, the increases in prevalence of rhinitis and eczema could not be entirely explained by the change of prevalence of these risk factors. The odds ratio OR for the study period remained significantly associated with current rhinitis (OR 1.31, 95% confidence intervals CI 1.17-1.46), current rhinoconjunctivitis (OR 1.63, 95% Cl 1.41-1.87) and life-time eczema (OR 1.30, 95% CI 1.16-1.45) after adjustment for these confounding variables using logistic regression model. Further study is warranted to elucidate the factors contributing to the observable change in the prevalence of rhinitis in our population.	24	74	2004	7	10.1046/j.0905-6157.2003.00109.x	Allergy; Immunology; Pediatrics
Respiratory symptoms and peak expiratory flow in children with asthma in relation to volatile organic compounds in exhaled breath and ambient air. Indoor volatile organic compounds (VOCs) have been associated with asthma, but there is little epidemiologic work on ambient exposures, and no data on relationships between respiratory health and exhaled breath VOCs, which is a biomarker of VOC exposure. We recruited 26 Hispanic children with mild asthma in a Los Angeles community with high VOC levels near major freeways and trucking routes. Two dropped out, three had invalid peak expiratory flow (PEF) or breath VOC data, leaving 21. Children filled out symptom diaries and performed PEF maneuvers daily, November 1999 January 2000. We aimed to collect breath VOC samples on asthma episode and baseline symptom-free days, but six subjects only gave samples on symptom-free days. We analyzed 106 breath samples by GC-MS. Eight VOCs were quanti. able in >75% of breath samples (benzene, methylene chloride, styrene, tetrachloroethylene, toluene, m,p-xylene, o-xylene, and p-dichlorobenzene). Generalized estimating equation and mixed linear regression models for VOC exposure-response relationships controlled for temperature and respiratory infections. We found marginally positive associations between bothersome or more severe asthma symptoms and same day breath concentrations of benzene [odds ratio ( OR) 2.03, 95% confidence interval (CI) 0.80, 5.11] but not other breath VOCs. Ambient petroleum-related VOCs measured on the same person-days as breath VOCs showed notably stronger associations with symptoms, including toluene, m,p-xylene, o-xylene, and benzene (OR 5.93, 95% CI 1.64, 21.4). On breath sample days, symptoms were also associated with 1-h ambient NO2, OR 8.13 (1.52, 43.4), and SO2, OR 2.36 (1.16, 4.81). Consistent inverse relationships were found between evening PEF and the same ambient VOCs, NO2, and SO2. There were no associations with O-3. Given the high traffic density of the region, stronger associations for ambient than for breath VOCs suggest that ambient VOC measurements were better markers for daily exposure to combustion-related compounds thought to be causally related to acute asthma. Alternatively, the low sample size of symptom responses (5-21 responses per 108 breath samples) may have led to the nonsignificant results for breath VOCs.. epidemiology| panel study| exposure biomarkers| hazardous air pollutants| air pollution|antiinflammatory medication use| pollutants| pollution| exposure| severity| indoor| models| exacerbations| associations| formaldehyde.	SEP-2003	epidemiology| panel study| exposure biomarkers| hazardous air pollutants| air pollution|antiinflammatory medication use| pollutants| pollution| exposure| severity| indoor| models| exacerbations| associations| formaldehyde	Delfino, RJ; Gong, H; Linn, WS; Hu, Y; Pellizzari, ED	Respiratory symptoms and peak expiratory flow in children with asthma in relation to volatile organic compounds in exhaled breath and ambient air		JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY	epidemiology; panel study; exposure biomarkers; hazardous air pollutants; air pollution	ANTIINFLAMMATORY MEDICATION USE; POLLUTANTS; POLLUTION; EXPOSURE; SEVERITY; INDOOR; MODELS; EXACERBATIONS; ASSOCIATIONS; FORMALDEHYDE	Indoor volatile organic compounds (VOCs) have been associated with asthma, but there is little epidemiologic work on ambient exposures, and no data on relationships between respiratory health and exhaled breath VOCs, which is a biomarker of VOC exposure. We recruited 26 Hispanic children with mild asthma in a Los Angeles community with high VOC levels near major freeways and trucking routes. Two dropped out, three had invalid peak expiratory flow (PEF) or breath VOC data, leaving 21. Children filled out symptom diaries and performed PEF maneuvers daily, November 1999 January 2000. We aimed to collect breath VOC samples on asthma episode and baseline symptom-free days, but six subjects only gave samples on symptom-free days. We analyzed 106 breath samples by GC-MS. Eight VOCs were quanti. able in >75% of breath samples (benzene, methylene chloride, styrene, tetrachloroethylene, toluene, m,p-xylene, o-xylene, and p-dichlorobenzene). Generalized estimating equation and mixed linear regression models for VOC exposure-response relationships controlled for temperature and respiratory infections. We found marginally positive associations between bothersome or more severe asthma symptoms and same day breath concentrations of benzene [odds ratio ( OR) 2.03, 95% confidence interval (CI) 0.80, 5.11] but not other breath VOCs. Ambient petroleum-related VOCs measured on the same person-days as breath VOCs showed notably stronger associations with symptoms, including toluene, m,p-xylene, o-xylene, and benzene (OR 5.93, 95% CI 1.64, 21.4). On breath sample days, symptoms were also associated with 1-h ambient NO2, OR 8.13 (1.52, 43.4), and SO2, OR 2.36 (1.16, 4.81). Consistent inverse relationships were found between evening PEF and the same ambient VOCs, NO2, and SO2. There were no associations with O-3. Given the high traffic density of the region, stronger associations for ambient than for breath VOCs suggest that ambient VOC measurements were better markers for daily exposure to combustion-related compounds thought to be causally related to acute asthma. Alternatively, the low sample size of symptom responses (5-21 responses per 108 breath samples) may have led to the nonsignificant results for breath VOCs.	40	74	2003	16	10.1038/sj.jea.7500287	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
The C-159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children. Activation of macrophages through CD14 by microbes is crucial in inducing immunity by type 1 T helper cells. A C-to-T polymorphism at position -159 of CD14 was associated with serum total IgE level in Caucasians but not in Japanese subjects. The objective of this study is to determine whether this polymorphic marker is associated with atopy and asthma phenotypes in Chinese children. Restriction fragment length polymorphism was used to characterize CD14/-159 genotypes. Microparticle immunoassay was used to measure serum total IgE level; fluorescent enzyme immunoassay was performed to measure serum concentrations of specific IgE to aeroallergens; and enzyme-linked immunosorbent assay was used to measure serum levels of soluble CD14 (sCD14). Lung function in asthmatics was assessed by spirometry. Two hundred and fifty-eight patients and 92 control children were recruited. Their mean serum total IgE concentrations were 331 and 74 kIU/l, respectively (p < 0.0001). Atopy, defined as the presence of at least one allergen-specific IgE in serum, was found in 220 (85%) patients and in 41 (45%) controls (p < 0.0001). Serum sCD14 levels were significantly associated with CD14/-159 genotypes (p = 0.004). Atopic subjects with CC genotype in CD14/-159 had the highest serum total IgE levels compared with CT and TT genotypes, with the respective mean values being 661, 427 and 380 kIU/l (p = 0.015). Similarly, a higher proportion of subjects with CC genotype had increased serum total IgE concentration (p = 0.039). This polymorphic marker was not associated with asthma or aeroallergen sensitization in our cohort. Our results suggest that the C-159T of CD14 was associated with serum total IgE concentration in atopic Chinese children.. atopy| cd14| chinese| immunoglobulin e|immunoglobulin-e| asthma| gene| endotoxin| childhood| exposure| linkage| markers| susceptibility| prevalence.	AUG-2003	atopy| cd14| chinese| immunoglobulin e|immunoglobulin-e| asthma| gene| endotoxin| childhood| exposure| linkage| markers| susceptibility| prevalence	Leung, TF; Tang, NLS; Sung, YM; Li, AM; Wong, GWK; Chan, IHS; Lam, CWK	The C-159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children		PEDIATRIC ALLERGY AND IMMUNOLOGY	atopy; CD14; Chinese; immunoglobulin E	IMMUNOGLOBULIN-E; ASTHMA; GENE; ENDOTOXIN; CHILDHOOD; EXPOSURE; LINKAGE; MARKERS; SUSCEPTIBILITY; PREVALENCE	Activation of macrophages through CD14 by microbes is crucial in inducing immunity by type 1 T helper cells. A C-to-T polymorphism at position -159 of CD14 was associated with serum total IgE level in Caucasians but not in Japanese subjects. The objective of this study is to determine whether this polymorphic marker is associated with atopy and asthma phenotypes in Chinese children. Restriction fragment length polymorphism was used to characterize CD14/-159 genotypes. Microparticle immunoassay was used to measure serum total IgE level; fluorescent enzyme immunoassay was performed to measure serum concentrations of specific IgE to aeroallergens; and enzyme-linked immunosorbent assay was used to measure serum levels of soluble CD14 (sCD14). Lung function in asthmatics was assessed by spirometry. Two hundred and fifty-eight patients and 92 control children were recruited. Their mean serum total IgE concentrations were 331 and 74 kIU/l, respectively (p < 0.0001). Atopy, defined as the presence of at least one allergen-specific IgE in serum, was found in 220 (85%) patients and in 41 (45%) controls (p < 0.0001). Serum sCD14 levels were significantly associated with CD14/-159 genotypes (p = 0.004). Atopic subjects with CC genotype in CD14/-159 had the highest serum total IgE levels compared with CT and TT genotypes, with the respective mean values being 661, 427 and 380 kIU/l (p = 0.015). Similarly, a higher proportion of subjects with CC genotype had increased serum total IgE concentration (p = 0.039). This polymorphic marker was not associated with asthma or aeroallergen sensitization in our cohort. Our results suggest that the C-159T of CD14 was associated with serum total IgE concentration in atopic Chinese children.	30	74	2003	6	10.1034/j.1399-3038.2003.00048.x	Allergy; Immunology; Pediatrics
Health impacts of pesticide exposure in a cohort of outdoor workers. We compared mortality of 1,999 outdoor staff working as part of an insecticide application program during 1935-1996 with that of 1,984 outdoor workers not occupationally exposed to insecticides, and with the Australian population. Surviving subjects also completed a morbidity questionnaire. Mortality was significantly higher in both exposed and control subjects compared with the Australian population. The major cause was mortality from smoking-related diseases. Mortality was also significantly increased in exposed subjects for a number of conditions that do not appear to be the result of smoking patterns. Compared with the general Australian population, mortality over the total study period was increased for asthma [standardized mortality ratio (SMR) = 3.45; 95% confidence interval (CI), 1.39-7.10] and for diabetes (SMR = 3.57; 95% CI, 1.16-8.32 for subjects working < 5 years). Mortality from pancreatic cancer was more frequent in subjects exposed to 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (SMR = 5.27; 95% CI, 1.09-15.40 for subjects working < 3 years). Compared with the control population, mortality from leukemia was increased in subjects working with more modern chemicals (standardized incidence ratio = 20.90; 95% CI, 1.54-284.41 for myeloid leukemia in the highest exposure group). There was also an increase in self-reported chronic illness and asthma, and lower neuropsychologic functioning scores among surviving exposed subjects when compared with controls. Diabetes was reported more commonly by subjects reporting occupational use of herbicides. These findings lend weight to other studies suggesting an association between adverse health effects and exposure to pesticides.. asthma| cohort study| ddt| diabetes| leukemia| neoplasms| pancreatic cancer| pesticides|pancreatic-cancer| organochlorine compounds| diabetes-mellitus| risk-factors| mortality| serum| leukemia| men| ddt.	MAY-2003	asthma| cohort study| ddt| diabetes| leukemia| neoplasms| pancreatic cancer| pesticides|pancreatic-cancer| organochlorine compounds| diabetes-mellitus| risk-factors| mortality| serum| leukemia| men| ddt	Beard, J; Sladden, T; Morgan, G; Berry, G; Brooks, L; McMichael, A	Health impacts of pesticide exposure in a cohort of outdoor workers		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; cohort study; DDT; diabetes; leukemia; neoplasms; pancreatic cancer; pesticides	PANCREATIC-CANCER; ORGANOCHLORINE COMPOUNDS; DIABETES-MELLITUS; RISK-FACTORS; MORTALITY; SERUM; LEUKEMIA; MEN; DDT	We compared mortality of 1,999 outdoor staff working as part of an insecticide application program during 1935-1996 with that of 1,984 outdoor workers not occupationally exposed to insecticides, and with the Australian population. Surviving subjects also completed a morbidity questionnaire. Mortality was significantly higher in both exposed and control subjects compared with the Australian population. The major cause was mortality from smoking-related diseases. Mortality was also significantly increased in exposed subjects for a number of conditions that do not appear to be the result of smoking patterns. Compared with the general Australian population, mortality over the total study period was increased for asthma [standardized mortality ratio (SMR) = 3.45; 95% confidence interval (CI), 1.39-7.10] and for diabetes (SMR = 3.57; 95% CI, 1.16-8.32 for subjects working < 5 years). Mortality from pancreatic cancer was more frequent in subjects exposed to 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (SMR = 5.27; 95% CI, 1.09-15.40 for subjects working < 3 years). Compared with the control population, mortality from leukemia was increased in subjects working with more modern chemicals (standardized incidence ratio = 20.90; 95% CI, 1.54-284.41 for myeloid leukemia in the highest exposure group). There was also an increase in self-reported chronic illness and asthma, and lower neuropsychologic functioning scores among surviving exposed subjects when compared with controls. Diabetes was reported more commonly by subjects reporting occupational use of herbicides. These findings lend weight to other studies suggesting an association between adverse health effects and exposure to pesticides.	33	74	2003	7	10.1289/ehp.5885	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
House dust mite allergen in US beds: Results from the first National Survey of Lead and Allergens in Housing. Background: Although exposure to house dust mite allergen is a major risk factor for allergic sensitization and asthma, nationwide estimates of dust mite allergen levels in US homes have not been reported. Objective: The purpose of this study was to estimate the prevalence of dust mite allergen in beds of US homes and to identify predictors of dust mite allergen concentration. Methods: Data were obtained from the first National Survey of Lead and Allergens in Housing, a cross-sectional survey of 831 permanently occupied noninstitutional housing units that permitted resident children. Dust mite allergen concentration (Der f 1 plus Der p 1) was determined from a dust sample collected from a bed. The percentages of homes with concentrations at or greater than detection, 2.0 mug/g bed dust, and 10.0 mug/g bed dust were estimated. Independent predictors of allergen concentration were assessed with multivariable linear regression. Results: The percentages of US homes with dust mite allergen concentrations at or greater than detection, 2.0 mug/g, and 10.0 mug/g were 84.2% (SE, 1.73), 46.2% (SE, 2.0), and 24.2% (SE, 2.1), respectively. Independent predictors of higher levels were older homes, non-West census regions, single-family homes, no resident children, lower household income, heating sources other than forced air, musty or mildew odor, and higher bedroom humidity. Conclusion: Most US homes have detectable levels of dust mite allergen in a bed. Levels previously associated with allergic sensitization and asthma are common in US bedrooms. Predictors can be used to identify conditions under which homes are more likely to have increased dust mite allergen levels.. house dust mite allergen| indoor allergens| surveys| epidemiology|reducing relative-humidity| der-p-i| indoor allergens| risk factor| avoidance measures| seasonal-variation| asthmatic-patients| childhood asthma| grass-pollen| exposure.	FEB-2003	house dust mite allergen| indoor allergens| surveys| epidemiology|reducing relative-humidity| der-p-i| indoor allergens| risk factor| avoidance measures| seasonal-variation| asthmatic-patients| childhood asthma| grass-pollen| exposure	Arbes, SJ; Cohn, RD; Yin, M; Muilenberg, ML; Burge, HA; Friedman, W; Zeldin, DC	House dust mite allergen in US beds: Results from the first National Survey of Lead and Allergens in Housing		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	house dust mite allergen; indoor allergens; surveys; epidemiology	REDUCING RELATIVE-HUMIDITY; DER-P-I; INDOOR ALLERGENS; RISK FACTOR; AVOIDANCE MEASURES; SEASONAL-VARIATION; ASTHMATIC-PATIENTS; CHILDHOOD ASTHMA; GRASS-POLLEN; EXPOSURE	Background: Although exposure to house dust mite allergen is a major risk factor for allergic sensitization and asthma, nationwide estimates of dust mite allergen levels in US homes have not been reported. Objective: The purpose of this study was to estimate the prevalence of dust mite allergen in beds of US homes and to identify predictors of dust mite allergen concentration. Methods: Data were obtained from the first National Survey of Lead and Allergens in Housing, a cross-sectional survey of 831 permanently occupied noninstitutional housing units that permitted resident children. Dust mite allergen concentration (Der f 1 plus Der p 1) was determined from a dust sample collected from a bed. The percentages of homes with concentrations at or greater than detection, 2.0 mug/g bed dust, and 10.0 mug/g bed dust were estimated. Independent predictors of allergen concentration were assessed with multivariable linear regression. Results: The percentages of US homes with dust mite allergen concentrations at or greater than detection, 2.0 mug/g, and 10.0 mug/g were 84.2% (SE, 1.73), 46.2% (SE, 2.0), and 24.2% (SE, 2.1), respectively. Independent predictors of higher levels were older homes, non-West census regions, single-family homes, no resident children, lower household income, heating sources other than forced air, musty or mildew odor, and higher bedroom humidity. Conclusion: Most US homes have detectable levels of dust mite allergen in a bed. Levels previously associated with allergic sensitization and asthma are common in US bedrooms. Predictors can be used to identify conditions under which homes are more likely to have increased dust mite allergen levels.	49	74	2003	7	10.1067/mai.2003.16	Allergy; Immunology
Prevalence of self-reported hypersensitivity to electric or magnetic fields in a population-based questionnaire survey. Objectives The prevalence of medically unexplained symptoms attributed to exposure to electromagnetic fields is still largely unknown. Previous studies have investigated reported hypersensitivity to electricity in selected groups recruited from workplaces or outpatient clinics. The aim of this study was to estimate the prevalence of self-reported hypersensitivity to electric or magnetic fields in the general population and to describe characteristics of the group reporting such hypersensitivity with regard to demographics, other complaints, hypersensitivities, and traditional allergies. Methods A cross-sectional questionnaire survey was conducted in 1997 among 15 000 men and women between 19 and 80 years of age in Stockholm County. The response rate was 73%. Results One and a half percent of the respondents reported hypersensitivity to electric or magnetic fields. Prevalence was highest among women and in the 60- to 69-year age group. The hypersensitive group reported all symptoms, allergies, and other types of hypersensitivities included in the survey (as well as being disturbed by various factors in the: home) to a significantly greater extent than the rest of the respondents. No specific symptom profile set off the hypersensitive group from the rest of the respondents. Conclusions The results should be interpreted with caution. But they suggest that there is widespread concern among the general population about risks to health posed by electric and magnetic fields. More research is warranted to explore ill health among people reporting hypersensitivity to electric or magnetic fields.. allergy| cross-sectional| hypersensitivity to electricity| symptoms|chemical odor intolerance| visual-display units| sensitivity| symptoms| individuals.	FEB-2002	allergy| cross-sectional| hypersensitivity to electricity| symptoms|chemical odor intolerance| visual-display units| sensitivity| symptoms| individuals	Hillert, L; Berglind, N; Arnetz, BB; Bellander, T	Prevalence of self-reported hypersensitivity to electric or magnetic fields in a population-based questionnaire survey		SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH	allergy; cross-sectional; hypersensitivity to electricity; symptoms	CHEMICAL ODOR INTOLERANCE; VISUAL-DISPLAY UNITS; SENSITIVITY; SYMPTOMS; INDIVIDUALS	Objectives The prevalence of medically unexplained symptoms attributed to exposure to electromagnetic fields is still largely unknown. Previous studies have investigated reported hypersensitivity to electricity in selected groups recruited from workplaces or outpatient clinics. The aim of this study was to estimate the prevalence of self-reported hypersensitivity to electric or magnetic fields in the general population and to describe characteristics of the group reporting such hypersensitivity with regard to demographics, other complaints, hypersensitivities, and traditional allergies. Methods A cross-sectional questionnaire survey was conducted in 1997 among 15 000 men and women between 19 and 80 years of age in Stockholm County. The response rate was 73%. Results One and a half percent of the respondents reported hypersensitivity to electric or magnetic fields. Prevalence was highest among women and in the 60- to 69-year age group. The hypersensitive group reported all symptoms, allergies, and other types of hypersensitivities included in the survey (as well as being disturbed by various factors in the: home) to a significantly greater extent than the rest of the respondents. No specific symptom profile set off the hypersensitive group from the rest of the respondents. Conclusions The results should be interpreted with caution. But they suggest that there is widespread concern among the general population about risks to health posed by electric and magnetic fields. More research is warranted to explore ill health among people reporting hypersensitivity to electric or magnetic fields.	21	74	2002	9		Public, Environmental & Occupational Health
Diisocyanate asthma: clinical aspects and immunopathogenesis. Diisocyanates, highly reactive chemicals used in the production of polyurethanes, are currently the most frequently reported cause of chemically induced occupational asthma and their use continues to rise. The prevalence of diisocyanate asthma among exposed workers is estimated to range from 5% to 15%. Routes of exposure include the respiratory tract and skin. Workplace exposures are difficult to quantify and control, and there is no simple diagnostic test for the disease. This review considers recent concepts in exposure, clinical aspects and pathogenesis of the disease. The pathogenesis of diisocyanate asthma remains unclear, with evidence supporting both immunological and noninummological mechanisms. Knowledge of the chemical reactivity of diisocyanates, the target biomolecules, and the cellular sites of reaction are fundamental to understanding diisocyanate toxicity and disease. Recent findings of chemical interactions with biological nucleophiles will be described. The importance of diisocyanate-adducted biomolecules will be emphasized and their potential contributions: to pathogenesis discussed. It is anticipated that greater understanding of the immunopathogenesis of diisocyanate asthma, including the initial cell/diisocyanate reactions, should lead to clinically useful markers of exposure and early disease. (C) 2002 Elsevier Science B.V. All rights reserved.. diisocyanate| asthma| adduct| airway hyperreactivity| immunopathogenesis| thiol reactions| occupational|induced occupational asthma| isocyanate-induced asthma| nonspecific bronchial hyperresponsiveness| dysfunction syndrome rads| peak expiratory flow| human serum-albumin| hla class-ii| toluene-diisocyanate| hexamethylene-diisocyanate| guinea-pigs.	FEB-2002	diisocyanate| asthma| adduct| airway hyperreactivity| immunopathogenesis| thiol reactions| occupational|induced occupational asthma| isocyanate-induced asthma| nonspecific bronchial hyperresponsiveness| dysfunction syndrome rads| peak expiratory flow| human serum-albumin| hla class-ii| toluene-diisocyanate| hexamethylene-diisocyanate| guinea-pigs	Redlich, CA; Karol, MH	Diisocyanate asthma: clinical aspects and immunopathogenesis		INTERNATIONAL IMMUNOPHARMACOLOGY	diisocyanate; asthma; adduct; airway hyperreactivity; immunopathogenesis; thiol reactions; occupational	INDUCED OCCUPATIONAL ASTHMA; ISOCYANATE-INDUCED ASTHMA; NONSPECIFIC BRONCHIAL HYPERRESPONSIVENESS; DYSFUNCTION SYNDROME RADS; PEAK EXPIRATORY FLOW; HUMAN SERUM-ALBUMIN; HLA CLASS-II; TOLUENE-DIISOCYANATE; HEXAMETHYLENE-DIISOCYANATE; GUINEA-PIGS	Diisocyanates, highly reactive chemicals used in the production of polyurethanes, are currently the most frequently reported cause of chemically induced occupational asthma and their use continues to rise. The prevalence of diisocyanate asthma among exposed workers is estimated to range from 5% to 15%. Routes of exposure include the respiratory tract and skin. Workplace exposures are difficult to quantify and control, and there is no simple diagnostic test for the disease. This review considers recent concepts in exposure, clinical aspects and pathogenesis of the disease. The pathogenesis of diisocyanate asthma remains unclear, with evidence supporting both immunological and noninummological mechanisms. Knowledge of the chemical reactivity of diisocyanates, the target biomolecules, and the cellular sites of reaction are fundamental to understanding diisocyanate toxicity and disease. Recent findings of chemical interactions with biological nucleophiles will be described. The importance of diisocyanate-adducted biomolecules will be emphasized and their potential contributions: to pathogenesis discussed. It is anticipated that greater understanding of the immunopathogenesis of diisocyanate asthma, including the initial cell/diisocyanate reactions, should lead to clinically useful markers of exposure and early disease. (C) 2002 Elsevier Science B.V. All rights reserved.	83	74	2002	12	10.1016/S1567-5769(01)00174-6	Immunology; Pharmacology & Pharmacy
Natural history of sensitization, symptoms and occupational diseases in apprentices exposed to laboratory animals. The natural history of the development of sensitization and disease due to high-molecular-weight allergens is not well characterized. This study describes the timecourse of the incidence of work-related symptoms, skin reactivity and occupational rhinoconjunctivitis (RC) and asthma (OA); and assesses the predictive value of skin testing and RC symptoms in apprentices exposed to laboratory animals, in a 3-4-yr programme. Four-hundred and seventeen apprentices at five institutions were assessed prospectively with questionnaire, skin-testing with animal-derived allergens, spirometry and airway responsiveness (n = 373). Depending on the school, students were seen 8 (n = 136), 20 (n = 345), 32 (n = 355) and 44 (n = 98) months after starting the programme. At all visits, the incidence was greater for work-related RC symptoms followed in order by skin reactivity, occupational RC, and, almost equally, OA and work-related respiratory symptoms. The incidence-density figures were comparable for each followup period and for most indices up to 32 months after entry into the study and then tended to decrease. The positive predictive values (PPVs) of skin reactivity to work-related allergens for the development of work-related RC and respiratory symptoms were 30% and 9.0%, respectively, while the PPVs of work-related RC for the development of OA was 11.4%. Sensitization, symptoms and diseases occur maximally in the first 2-3 yrs after starting exposure to laboratory animals. Skin reactivity to work-related allergens and rhinoconjuctivitis symptoms have low positive predictive values.. asthma| immunological sensitization| occupational asthma|determinants| methacholine| asthma| agents| volume| atopy| tests.	MAY-2001	asthma| immunological sensitization| occupational asthma|determinants| methacholine| asthma| agents| volume| atopy| tests	Gautrin, D; Ghezzo, H; Infante-Rivard, C; Malo, JL	Natural history of sensitization, symptoms and occupational diseases in apprentices exposed to laboratory animals		EUROPEAN RESPIRATORY JOURNAL	asthma; immunological sensitization; occupational asthma	DETERMINANTS; METHACHOLINE; ASTHMA; AGENTS; VOLUME; ATOPY; TESTS	The natural history of the development of sensitization and disease due to high-molecular-weight allergens is not well characterized. This study describes the timecourse of the incidence of work-related symptoms, skin reactivity and occupational rhinoconjunctivitis (RC) and asthma (OA); and assesses the predictive value of skin testing and RC symptoms in apprentices exposed to laboratory animals, in a 3-4-yr programme. Four-hundred and seventeen apprentices at five institutions were assessed prospectively with questionnaire, skin-testing with animal-derived allergens, spirometry and airway responsiveness (n = 373). Depending on the school, students were seen 8 (n = 136), 20 (n = 345), 32 (n = 355) and 44 (n = 98) months after starting the programme. At all visits, the incidence was greater for work-related RC symptoms followed in order by skin reactivity, occupational RC, and, almost equally, OA and work-related respiratory symptoms. The incidence-density figures were comparable for each followup period and for most indices up to 32 months after entry into the study and then tended to decrease. The positive predictive values (PPVs) of skin reactivity to work-related allergens for the development of work-related RC and respiratory symptoms were 30% and 9.0%, respectively, while the PPVs of work-related RC for the development of OA was 11.4%. Sensitization, symptoms and diseases occur maximally in the first 2-3 yrs after starting exposure to laboratory animals. Skin reactivity to work-related allergens and rhinoconjuctivitis symptoms have low positive predictive values.	16	74	2001	5	10.1183/09031936.01.17509040	Respiratory System
Association between air pollution and daily consultations with general practitioners for allergic rhinitis in London, United Kingdom. Few published studies have looked at the health effects of air pollution in the primary care setting, and most have concentrated on lower rather than upper respiratory diseases, The authors investigated the association of daily consultations with general practitioners for allergic rhinitis with air pollution in London, United Kingdom. Generalized additive models were used to regress time series of daily numbers of patients consulting for allergic rhinitis against 1992-1994 measures of air pollution, after control for possible confounders and adjustment for overdispersion and serial correlation. In children, a 10th-90th percentile increase in sulfur dioxide (SO(3)) levels 4 days prior to consultation (13-31 mug/m(3)) was associated with a 24.5% increase in consultations (95% confidence interval: 14.6, 35.2; p < 0.00001); a 10th-90th percentile increase in averaged ozone (O(3)) concentrations on the day of consultation and the preceding 3 days (6-29 parts per billion) was associated with a 37.6% rise (95% confidence interval: 23,3, 53.5; p < 0,00001). For adults, smaller effect sizes were observed for SO(3) and O(3). The association with SO(3) remained highly significant in the presence of other pollutants. This study suggests that air pollution worsens allergic rhinitis symptoms, leading to substantial increases in consultations. SO(3) and O(3) seem particularly responsible, and both seem to contribute independently.. air pollutants| air pollution| family practice| ozone| primary health care| rhinitis| sulfur dioxide|time-series| hay-fever| prevalence| disorders| computer| asthma.	APR 1-2001	air pollutants| air pollution| family practice| ozone| primary health care| rhinitis| sulfur dioxide|time-series| hay-fever| prevalence| disorders| computer| asthma	Hajat, S; Haines, A; Atkinson, RW; Bremner, SA; Anderson, HR; Emberlin, J	Association between air pollution and daily consultations with general practitioners for allergic rhinitis in London, United Kingdom		AMERICAN JOURNAL OF EPIDEMIOLOGY	air pollutants; air pollution; family practice; ozone; primary health care; rhinitis; sulfur dioxide	TIME-SERIES; HAY-FEVER; PREVALENCE; DISORDERS; COMPUTER; ASTHMA	Few published studies have looked at the health effects of air pollution in the primary care setting, and most have concentrated on lower rather than upper respiratory diseases, The authors investigated the association of daily consultations with general practitioners for allergic rhinitis with air pollution in London, United Kingdom. Generalized additive models were used to regress time series of daily numbers of patients consulting for allergic rhinitis against 1992-1994 measures of air pollution, after control for possible confounders and adjustment for overdispersion and serial correlation. In children, a 10th-90th percentile increase in sulfur dioxide (SO(3)) levels 4 days prior to consultation (13-31 mug/m(3)) was associated with a 24.5% increase in consultations (95% confidence interval: 14.6, 35.2; p < 0.00001); a 10th-90th percentile increase in averaged ozone (O(3)) concentrations on the day of consultation and the preceding 3 days (6-29 parts per billion) was associated with a 37.6% rise (95% confidence interval: 23,3, 53.5; p < 0,00001). For adults, smaller effect sizes were observed for SO(3) and O(3). The association with SO(3) remained highly significant in the presence of other pollutants. This study suggests that air pollution worsens allergic rhinitis symptoms, leading to substantial increases in consultations. SO(3) and O(3) seem particularly responsible, and both seem to contribute independently.	19	74	2001	11	10.1093/aje/153.7.704	Public, Environmental & Occupational Health
Residential exposures associated with asthma in US children. Objective. Residential exposures are recognized risk factors for childhood asthma, but the relative contribution of specific risk factors and the overall contribution of housing to asthma in US children is unknown. The objective of this study was to identify risk factors and estimate the population attributable risk of residential exposures for doctor-diagnosed asthma for US children. Methods. A cross-sectional survey was conducted from 1988 to 1994. Survey participants were 8257 children who were <6 years old and who participated in the Third National Health and Nutrition Examination Survey, a survey of the health and nutritional status of children and adults in the United States. The main outcome measure was doctor-diagnosed asthma, as reported by the parent. Results. Six percent of children had doctor-diagnosed asthma. The prevalence of asthma was higher among boys (6.7%) than girls (5.1%) and was higher among black children (8.9%) than white children (5.2%). Risk factors for doctor-diagnosed asthma included a family history of atopy (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.5, 3.1), child's history of allergy to a pet (OR: 24.2; 95% CI: 8.4, 69.5), exposure to environmental tobacco smoke (OR: 1.8; 95% CI: 1.2-2.6), use of a gas stove or oven for heat (OR: 1.8; 95% CI: 1.02-3.2), and presence of a dog in the household (OR: 1.6; 95% CI: 1.1, 2.3). The population attributable risk of <greater than or equal to>1 residential exposure for doctor-diagnosed asthma in US children <6 years old was 39.2%, or an estimated 533 000 excess cases, whereas having a family history of atopy accounted for 300 000. The attributable cost of asthma as a result of residential exposures for children <6 years old was $402 million (95% CI: $296-$507 million) annually. Conclusions. The elimination of identified residential risk factors, if causally associated with asthma, would result in a 39% decline in doctor-diagnosed asthma among US children <6 years old.. nhanes| children| pediatric| prevention| epidemiology| allergic rhinitis| medical costs| day care| housing| pets and environment|childhood asthma| parental smoking| risk-factors| respiratory symptoms| indoor allergens| sensitization| health| prevalence| morbidity| tobacco.	MAR-2001	nhanes| children| pediatric| prevention| epidemiology| allergic rhinitis| medical costs| day care| housing| pets and environment|childhood asthma| parental smoking| risk-factors| respiratory symptoms| indoor allergens| sensitization| health| prevalence| morbidity| tobacco	Lanphear, BP; Aligne, CA; Auinger, P; Weitzman, M; Byrd, RS	Residential exposures associated with asthma in US children		PEDIATRICS	NHANES; children; pediatric; prevention; epidemiology; allergic rhinitis; medical costs; day care; housing; pets and environment	CHILDHOOD ASTHMA; PARENTAL SMOKING; RISK-FACTORS; RESPIRATORY SYMPTOMS; INDOOR ALLERGENS; SENSITIZATION; HEALTH; PREVALENCE; MORBIDITY; TOBACCO	Objective. Residential exposures are recognized risk factors for childhood asthma, but the relative contribution of specific risk factors and the overall contribution of housing to asthma in US children is unknown. The objective of this study was to identify risk factors and estimate the population attributable risk of residential exposures for doctor-diagnosed asthma for US children. Methods. A cross-sectional survey was conducted from 1988 to 1994. Survey participants were 8257 children who were <6 years old and who participated in the Third National Health and Nutrition Examination Survey, a survey of the health and nutritional status of children and adults in the United States. The main outcome measure was doctor-diagnosed asthma, as reported by the parent. Results. Six percent of children had doctor-diagnosed asthma. The prevalence of asthma was higher among boys (6.7%) than girls (5.1%) and was higher among black children (8.9%) than white children (5.2%). Risk factors for doctor-diagnosed asthma included a family history of atopy (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.5, 3.1), child's history of allergy to a pet (OR: 24.2; 95% CI: 8.4, 69.5), exposure to environmental tobacco smoke (OR: 1.8; 95% CI: 1.2-2.6), use of a gas stove or oven for heat (OR: 1.8; 95% CI: 1.02-3.2), and presence of a dog in the household (OR: 1.6; 95% CI: 1.1, 2.3). The population attributable risk of <greater than or equal to>1 residential exposure for doctor-diagnosed asthma in US children <6 years old was 39.2%, or an estimated 533 000 excess cases, whereas having a family history of atopy accounted for 300 000. The attributable cost of asthma as a result of residential exposures for children <6 years old was $402 million (95% CI: $296-$507 million) annually. Conclusions. The elimination of identified residential risk factors, if causally associated with asthma, would result in a 39% decline in doctor-diagnosed asthma among US children <6 years old.	41	74	2001	7	10.1542/peds.107.3.505	Pediatrics
Benefits and risks of sauna bathing. Although sauna bathing causes various acute, transient cardiovascular and hormonal changes, it is well tolerated by most healthy adults and children. Sauna bathing does not influence fertility and is safe during the uncomplicated pregnancies of healthy women. Some studies have suggested that long-term sauna bathing may help lower blood pressure in patients with hypertension and improve the left ventricular ejection fraction in patients with chronic congestive heart failure, but additional data are needed to confirm these findings. The transient improvements in pulmonary function that occur in the sauna may provide some relief to patients with asthma and chronic bronchitis. Sauna bathing may also alleviate pain and improve joint mobility in patients with rheumatic disease. Although sauna bathing does not cause drying of the skin-and may even benefit patients with psoriasis-sweating may increase itching in patients with atopic dermatitis. Contraindications to sauna bathing include unstable angina pectoris, recent myocardial infarction, and severe aortic stenosis. Sauna bathing is safe, however, for most people with coronary heart disease with stable angina pectoris or old myocardial infarction. Very few acute myocardial infarctions and sudden deaths occur in saunas, but alcohol consumption during sauna bathing increases the risk of hypotension, arrhythmia, and sudden death, and should be avoided. (C) 2001 by Excerpta Medica, Inc.. high ambient-temperature| sudden coronary death| plasma-renin activity| finnish sauna| heat exposure| thermal-stress| hypertensive patients| beta-endorphin| triplochiton scleroxylon| maternal hyperthermia.	FEB 1-2001	high ambient-temperature| sudden coronary death| plasma-renin activity| finnish sauna| heat exposure| thermal-stress| hypertensive patients| beta-endorphin| triplochiton scleroxylon| maternal hyperthermia	Hannuksela, ML; Ellahham, S	Benefits and risks of sauna bathing		AMERICAN JOURNAL OF MEDICINE		HIGH AMBIENT-TEMPERATURE; SUDDEN CORONARY DEATH; PLASMA-RENIN ACTIVITY; FINNISH SAUNA; HEAT EXPOSURE; THERMAL-STRESS; HYPERTENSIVE PATIENTS; BETA-ENDORPHIN; TRIPLOCHITON SCLEROXYLON; MATERNAL HYPERTHERMIA	Although sauna bathing causes various acute, transient cardiovascular and hormonal changes, it is well tolerated by most healthy adults and children. Sauna bathing does not influence fertility and is safe during the uncomplicated pregnancies of healthy women. Some studies have suggested that long-term sauna bathing may help lower blood pressure in patients with hypertension and improve the left ventricular ejection fraction in patients with chronic congestive heart failure, but additional data are needed to confirm these findings. The transient improvements in pulmonary function that occur in the sauna may provide some relief to patients with asthma and chronic bronchitis. Sauna bathing may also alleviate pain and improve joint mobility in patients with rheumatic disease. Although sauna bathing does not cause drying of the skin-and may even benefit patients with psoriasis-sweating may increase itching in patients with atopic dermatitis. Contraindications to sauna bathing include unstable angina pectoris, recent myocardial infarction, and severe aortic stenosis. Sauna bathing is safe, however, for most people with coronary heart disease with stable angina pectoris or old myocardial infarction. Very few acute myocardial infarctions and sudden deaths occur in saunas, but alcohol consumption during sauna bathing increases the risk of hypotension, arrhythmia, and sudden death, and should be avoided. (C) 2001 by Excerpta Medica, Inc.	128	74	2001	9	10.1016/S0002-9343(00)00671-9	General & Internal Medicine
Increased nitric oxide in exhaled air after intake of a nitrate-rich meal. Exhaled and nasal NO (ENO, NNO) have been suggested as markers for inflammation in lower and upper respiratory tract respectively. It is still unknown how a number of factors, apart from airway inflammation, can influence NO levels. The aim of this study was to determine the effect of a nitrate-rich meal on ENO and NNO. Sixteen healthy subjects were observed during 1 week on normal diet before a nitrate-restricted diet was introduced in the next. On day 3 of the second week they were made to ingest a nitrate rich meal. ENO, NNO, plasma nitrate and plasma L-arginine were followed before the meal and afterwards for 3 h. ENO and NNO as well as plasma nitrate and plasma L-arginine were significantly elevated after the nitrate-rich meal. The median maximal increase of ENO and NNO was 47% and 13% respectively. We found a moderate but significant correlation between the rise in plasma nitrate and ENO (r(s)=0.57, P=0.027) but none between plasma nitrate and NNO (r(s)=-0.02, P=0.95). As nitrate in the diet seems to substantially influence the levels of ENO it is important either to restrictor register the intake of nitrate-rich food prior to measuring ENO.. nitric oxide| nasal nitric oxide| nitrate| nitrite| l-arginine| breath analysis|l-arginine| human-saliva| asthma| nasal| generation| rhinitis| mass.	FEB-2001	nitric oxide| nasal nitric oxide| nitrate| nitrite| l-arginine| breath analysis|l-arginine| human-saliva| asthma| nasal| generation| rhinitis| mass	Olin, AC; Aldenbratt, A; Ekman, A; Ljungkvist, G; Jungersten, L; Alving, K; Toren, K	Increased nitric oxide in exhaled air after intake of a nitrate-rich meal		RESPIRATORY MEDICINE	nitric oxide; nasal nitric oxide; nitrate; nitrite; L-arginine; breath analysis	L-ARGININE; HUMAN-SALIVA; ASTHMA; NASAL; GENERATION; RHINITIS; MASS	Exhaled and nasal NO (ENO, NNO) have been suggested as markers for inflammation in lower and upper respiratory tract respectively. It is still unknown how a number of factors, apart from airway inflammation, can influence NO levels. The aim of this study was to determine the effect of a nitrate-rich meal on ENO and NNO. Sixteen healthy subjects were observed during 1 week on normal diet before a nitrate-restricted diet was introduced in the next. On day 3 of the second week they were made to ingest a nitrate rich meal. ENO, NNO, plasma nitrate and plasma L-arginine were followed before the meal and afterwards for 3 h. ENO and NNO as well as plasma nitrate and plasma L-arginine were significantly elevated after the nitrate-rich meal. The median maximal increase of ENO and NNO was 47% and 13% respectively. We found a moderate but significant correlation between the rise in plasma nitrate and ENO (r(s)=0.57, P=0.027) but none between plasma nitrate and NNO (r(s)=-0.02, P=0.95). As nitrate in the diet seems to substantially influence the levels of ENO it is important either to restrictor register the intake of nitrate-rich food prior to measuring ENO.	30	74	2001	6	10.1053/rmed.2000.1010	Cardiovascular System & Cardiology; Respiratory System
(1 -> 3)-beta-D-glucan - relationship to indoor air-related symptoms, allergy and asthma. (1 --> 3)-beta -D-glucan is a polyglucose structure in the cell wall of moulds, some bacteria and plants. Due to its unique (1 --> 3)-beta linkage it binds to specific receptors on phagocytosing cells and induces changes in their metabolism. Under realistic environmental concentrations, available data suggest that these changes express themselves as alterations of the defense mechanisms to other agents. Inhalation of (I --> 3)-beta -D-glucan in humans causes symptoms from the upper respiratory tract and induction of cytokines in blood monocytes. (1 --> 3)-beta -D-glucan can be used as a marker of mould biomass in field studies. Relationships between the amount of (1 --> 3)-beta -D-glucan and the extent of symptoms as well as lung function changes and inflammatory markers have been described. In view of the mechanisms involved in the normal development of the immune system, children seem to be a particular group at risk due to (I --> 3)-beta -D-glucan exposure. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.. moulds| airways inflammation| respiratory symptoms| (1 -> 3)-beta-d-glucan|airways inflammation| endotoxin| glucan| (1->3)-beta-d-glucan| interleukin-1| inhalation| airborne| atopy.	NOV 2-2000	moulds| airways inflammation| respiratory symptoms| (1 -> 3)-beta-d-glucan|airways inflammation| endotoxin| glucan| (1->3)-beta-d-glucan| interleukin-1| inhalation| airborne| atopy	Rylander, R; Lin, RH	(1 -> 3)-beta-D-glucan - relationship to indoor air-related symptoms, allergy and asthma		TOXICOLOGY	moulds; airways inflammation; respiratory symptoms; (1 -> 3)-beta-D-glucan	AIRWAYS INFLAMMATION; ENDOTOXIN; GLUCAN; (1->3)-BETA-D-GLUCAN; INTERLEUKIN-1; INHALATION; AIRBORNE; ATOPY	(1 --> 3)-beta -D-glucan is a polyglucose structure in the cell wall of moulds, some bacteria and plants. Due to its unique (1 --> 3)-beta linkage it binds to specific receptors on phagocytosing cells and induces changes in their metabolism. Under realistic environmental concentrations, available data suggest that these changes express themselves as alterations of the defense mechanisms to other agents. Inhalation of (I --> 3)-beta -D-glucan in humans causes symptoms from the upper respiratory tract and induction of cytokines in blood monocytes. (1 --> 3)-beta -D-glucan can be used as a marker of mould biomass in field studies. Relationships between the amount of (1 --> 3)-beta -D-glucan and the extent of symptoms as well as lung function changes and inflammatory markers have been described. In view of the mechanisms involved in the normal development of the immune system, children seem to be a particular group at risk due to (I --> 3)-beta -D-glucan exposure. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.	29	74	2000	6	10.1016/S0300-483X(00)00291-2	Pharmacology & Pharmacy; Toxicology
Comparative effects of long-acting beta(2)-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma. Background: Exercise-induced asthma (EIA) is a common problem that can be controlled with long-acting beta-agonists and leukotriene-modifying compounds. There is, however, limited information on the comparative effectiveness of the two classes of drugs, as well as the relative potencies of the antileukotriene agents. Objective: The purpose of the present study was to provide data on the above issues. Methods: We performed a random-order, blinded, double-dummy, placebo-controlled trial in 10 patients with EIA. Each subject received standard single doses of salmeterol, montelukast, zafirlukast, zileuton, and placebo on separate days. The participants performed 4 minutes of cycle ergometry while breathing frigid air 1, 4, 8, and 12 hours after administration of the test agents. The primary endpoint was the extent of the decrement in the FEV1 10 minutes after exertion. Results: With placebo, symptomatic airway narrowing developed at all times (mean +/- SE decrease in FEV1 ranged between 21% +/- 5% and 26% +/- 5%). Salmeterol acted quickly and significantly blunted the obstructive response for 12 hours (Delta FEV1 first hour: 8% +/- 3%; Delta FEV1 twelfth hour: 8% +/- 3%; P < .0001 vs placebo and P = .72 vs time). The leukotriene-modifying agents produced effects within 1 hour of ingestion. Like salmeterol, montelukast and zafirlukast also offered long-lasting protection, and there were no significant differences between them (montelukast Delta FEV1 twelfth hour: 9% +/- 4%; zafirlukast Delta FEV1 twelfth hour: 11% +/- 2%; P = .75) or the beta(2)-agonist (montelukast vs salmeterol: P = .72; zafirlukast vs salmeterol: P = .48). Zileuton provided equivalent prophylaxis for the first 4 hours (Delta FEV1 fourth hour: 11% +/- 2%); however, by 8 hours, it was less efficacious than all of the other active compounds, and by 12 hours it did not differ from placebo (Delta FEV1 twelfth hour: 19% +/- 4%; P = .33). Conclusions: Single doses of the currently available leukotriene receptor antagonists provide prompt effective and persistent defense against EIA that equals that seen with a long-acting beta(2)-agonist. The synthesis inhibitor zileuton affords a comparable magnitude of prophylaxis but has a considerably shorter duration of action.. exercise-induced asthma| beta(2)-agonist| leukotriene receptor antagonist| 5-lipoxygenase inhibitor|induced bronchoconstriction| induced bronchospasm| refractory period| montelukast| salmeterol| children| zafirlukast| protection| duration.	SEP-2000	exercise-induced asthma| beta(2)-agonist| leukotriene receptor antagonist| 5-lipoxygenase inhibitor|induced bronchoconstriction| induced bronchospasm| refractory period| montelukast| salmeterol| children| zafirlukast| protection| duration	Coreno, A; Skowronski, M; Kotaru, C; McFadden, ER	Comparative effects of long-acting beta(2)-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	exercise-induced asthma; beta(2)-agonist; leukotriene receptor antagonist; 5-lipoxygenase inhibitor	INDUCED BRONCHOCONSTRICTION; INDUCED BRONCHOSPASM; REFRACTORY PERIOD; MONTELUKAST; SALMETEROL; CHILDREN; ZAFIRLUKAST; PROTECTION; DURATION	Background: Exercise-induced asthma (EIA) is a common problem that can be controlled with long-acting beta-agonists and leukotriene-modifying compounds. There is, however, limited information on the comparative effectiveness of the two classes of drugs, as well as the relative potencies of the antileukotriene agents. Objective: The purpose of the present study was to provide data on the above issues. Methods: We performed a random-order, blinded, double-dummy, placebo-controlled trial in 10 patients with EIA. Each subject received standard single doses of salmeterol, montelukast, zafirlukast, zileuton, and placebo on separate days. The participants performed 4 minutes of cycle ergometry while breathing frigid air 1, 4, 8, and 12 hours after administration of the test agents. The primary endpoint was the extent of the decrement in the FEV1 10 minutes after exertion. Results: With placebo, symptomatic airway narrowing developed at all times (mean +/- SE decrease in FEV1 ranged between 21% +/- 5% and 26% +/- 5%). Salmeterol acted quickly and significantly blunted the obstructive response for 12 hours (Delta FEV1 first hour: 8% +/- 3%; Delta FEV1 twelfth hour: 8% +/- 3%; P < .0001 vs placebo and P = .72 vs time). The leukotriene-modifying agents produced effects within 1 hour of ingestion. Like salmeterol, montelukast and zafirlukast also offered long-lasting protection, and there were no significant differences between them (montelukast Delta FEV1 twelfth hour: 9% +/- 4%; zafirlukast Delta FEV1 twelfth hour: 11% +/- 2%; P = .75) or the beta(2)-agonist (montelukast vs salmeterol: P = .72; zafirlukast vs salmeterol: P = .48). Zileuton provided equivalent prophylaxis for the first 4 hours (Delta FEV1 fourth hour: 11% +/- 2%); however, by 8 hours, it was less efficacious than all of the other active compounds, and by 12 hours it did not differ from placebo (Delta FEV1 twelfth hour: 19% +/- 4%; P = .33). Conclusions: Single doses of the currently available leukotriene receptor antagonists provide prompt effective and persistent defense against EIA that equals that seen with a long-acting beta(2)-agonist. The synthesis inhibitor zileuton affords a comparable magnitude of prophylaxis but has a considerably shorter duration of action.	23	74	2000	7		Allergy; Immunology
Interaction of tobacco-specific toxicants with the neuronal or, nicotinic acetylcholine receptor and its associated mitogenic signal transduction pathway: potential role in lung carcinogenesis and pediatric lung disorders. Pulmonary neuroendocrine cells function as hypoxia-sensitive chemoreceptors, and they release peptides and biogenic amines that are important mediators of pulmonary neonatal adaptation. Some of these products additionally act as autocrine growth factors. Increased numbers of pulmonary neuroendocrine cells have been observed in several smoking-associated pediatric lung disorders such as bronchopulmonary dysplasia, cystic fibrosis, sudden infant death syndrome, and asthma. Disturbed pulmonary neuroendocrine function has been implicated in the etiology of this disease complex. One of the most common smoking-associated lung cancer types, small cell lung carcinoma, expresses phenotypic and functional features of pulmonary neuroendocrine cells. We, as well as others, have shown that the release of the autocrine growth factors 5-hydroxytryptamine (5-HT, serotonin) and mammalian bombesisn/gastrin releasing peptide (MB/GRP) by cell lines derived from human small cell lung carcinoma or fetal hamster pulmonary neuroendocrine cells are regulated by a neuronal nicotinic acetylcholine receptor comprised of alpha(7) subunits. In radio-receptor assays, nicotine and the nicotine-derived carcinogenic nitrosamines N'-nictrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) bound with high affinity to this receptor with affinitites NNK > nicotine > NNN. Binding of nicotine or NNK to the alpha(7) receptor resulted in calcium influx and overexpression and activation of the serine-threonine protein kinase Raf-1. In turn, this event lead to overexpression and activation of the mitogen activated (MAP) kinases extracellular signal regulated kinase 1 (ERK1) and extracellular signal regulated kinase 2 (ERK2) and stimulation of DNA synthesis accompanied by an increase in cell numbers in fetal pulmonary neuroendocrine cells and small cell carcinoma cells. Exposure of fetal pulmonary neuroendocrine cells for 6 days to NNK caused a prominant up-regulation of Raf-1. Our findings suggest that chronic exposure to nicotine and NNK in pregnant women who smoke may up-regulate the alpha(7) nicotinic receptor as well as components of its associated mitogenic signal transduction pathway, thus increasing the susceptibilities of the infants for the development of pediatric lung disorders. Similarly, up-regulation of one or several components of this nicotinic receptor pathway in smokers may be an important factor for the development of small cell lung carcinoma. (C) 2000 Elsevier Science B.V. All rights reserved.. alpha 7 nicotinic receptor| nicotine| nicotine-derived nitrosamine| small cell lung carcinoma| pulmonary neuroendocrine cell| mitogenic signal transduction|infant-death-syndrome| pulmonary neuroendocrine cells| gastrin-releasing peptide| maternal smoking| functional expression| carcinoma cells| endocrine-cells| calcium-channel| carbon-dioxide| risk-factors.	MAR 30-2000	alpha 7 nicotinic receptor| nicotine| nicotine-derived nitrosamine| small cell lung carcinoma| pulmonary neuroendocrine cell| mitogenic signal transduction|infant-death-syndrome| pulmonary neuroendocrine cells| gastrin-releasing peptide| maternal smoking| functional expression| carcinoma cells| endocrine-cells| calcium-channel| carbon-dioxide| risk-factors	Schuller, HM; Jull, BA; Sheppard, BJ; Plummer, HK	Interaction of tobacco-specific toxicants with the neuronal or, nicotinic acetylcholine receptor and its associated mitogenic signal transduction pathway: potential role in lung carcinogenesis and pediatric lung disorders		EUROPEAN JOURNAL OF PHARMACOLOGY	alpha 7 nicotinic receptor; nicotine; nicotine-derived nitrosamine; small cell lung carcinoma; pulmonary neuroendocrine cell; mitogenic signal transduction	INFANT-DEATH-SYNDROME; PULMONARY NEUROENDOCRINE CELLS; GASTRIN-RELEASING PEPTIDE; MATERNAL SMOKING; FUNCTIONAL EXPRESSION; CARCINOMA CELLS; ENDOCRINE-CELLS; CALCIUM-CHANNEL; CARBON-DIOXIDE; RISK-FACTORS	Pulmonary neuroendocrine cells function as hypoxia-sensitive chemoreceptors, and they release peptides and biogenic amines that are important mediators of pulmonary neonatal adaptation. Some of these products additionally act as autocrine growth factors. Increased numbers of pulmonary neuroendocrine cells have been observed in several smoking-associated pediatric lung disorders such as bronchopulmonary dysplasia, cystic fibrosis, sudden infant death syndrome, and asthma. Disturbed pulmonary neuroendocrine function has been implicated in the etiology of this disease complex. One of the most common smoking-associated lung cancer types, small cell lung carcinoma, expresses phenotypic and functional features of pulmonary neuroendocrine cells. We, as well as others, have shown that the release of the autocrine growth factors 5-hydroxytryptamine (5-HT, serotonin) and mammalian bombesisn/gastrin releasing peptide (MB/GRP) by cell lines derived from human small cell lung carcinoma or fetal hamster pulmonary neuroendocrine cells are regulated by a neuronal nicotinic acetylcholine receptor comprised of alpha(7) subunits. In radio-receptor assays, nicotine and the nicotine-derived carcinogenic nitrosamines N'-nictrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) bound with high affinity to this receptor with affinitites NNK > nicotine > NNN. Binding of nicotine or NNK to the alpha(7) receptor resulted in calcium influx and overexpression and activation of the serine-threonine protein kinase Raf-1. In turn, this event lead to overexpression and activation of the mitogen activated (MAP) kinases extracellular signal regulated kinase 1 (ERK1) and extracellular signal regulated kinase 2 (ERK2) and stimulation of DNA synthesis accompanied by an increase in cell numbers in fetal pulmonary neuroendocrine cells and small cell carcinoma cells. Exposure of fetal pulmonary neuroendocrine cells for 6 days to NNK caused a prominant up-regulation of Raf-1. Our findings suggest that chronic exposure to nicotine and NNK in pregnant women who smoke may up-regulate the alpha(7) nicotinic receptor as well as components of its associated mitogenic signal transduction pathway, thus increasing the susceptibilities of the infants for the development of pediatric lung disorders. Similarly, up-regulation of one or several components of this nicotinic receptor pathway in smokers may be an important factor for the development of small cell lung carcinoma. (C) 2000 Elsevier Science B.V. All rights reserved.	73	74	2000	13	10.1016/S0014-2999(00)00094-7	Pharmacology & Pharmacy
Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. Background: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. Objective: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. Methods: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. Results: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were (sic)3800, an amount that was largely misspent. Conclusion: Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance.. allergic rhinitis| specific allergen immunotherapy| subcutaneous| sublingual| subcutaneous allergen immunotherapy| sublingual allergen immunotherapy| persistence| compliance| adherence| cost|term clinical-efficacy| quantitative assessment| slit formulation| easy project| rhinitis| adherence| asthma| medication| children| impact.	AUG-2013	allergic rhinitis| specific allergen immunotherapy| subcutaneous| sublingual| subcutaneous allergen immunotherapy| sublingual allergen immunotherapy| persistence| compliance| adherence| cost|term clinical-efficacy| quantitative assessment| slit formulation| easy project| rhinitis| adherence| asthma| medication| children| impact	Kiel, MA; Roder, E; van Wijk, RG; Al, MJ; Hop, WCJ; Rutten-van Molken, MPMH	Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergic rhinitis; specific allergen immunotherapy; subcutaneous; sublingual; subcutaneous allergen immunotherapy; sublingual allergen immunotherapy; persistence; compliance; adherence; cost	TERM CLINICAL-EFFICACY; QUANTITATIVE ASSESSMENT; SLIT FORMULATION; EASY PROJECT; RHINITIS; ADHERENCE; ASTHMA; MEDICATION; CHILDREN; IMPACT	Background: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. Objective: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. Methods: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. Results: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were (sic)3800, an amount that was largely misspent. Conclusion: Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance.	27	73	2013	10	10.1016/j.jaci.2013.03.013	Allergy; Immunology
Insights into the initiation of type 2 immune responses. Type 2 immune responses, characterized by the differentiation of CD4(+) T helper type 2 (Th2) cells and the production of the type 2 cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, are associated with parasitic helminth infections and inflammatory conditions such as asthma and allergies. Until recently the initiating factors associated with type 2 responses had been poorly understood. This review addresses the recent advances in identifying the diverse range of antigens/allergens associated with type 2 responses and the function, expression and sources of type-2-initiating cytokines (thymic stromal lymphopoietin, IL-25 and IL-33). We also discuss the latest findings regarding innate lymphoid cells, such as nuocytes, as early sources of type 2 cytokines and their importance in protective immunity to helminth infections. These developments represent major breakthroughs in our understanding of type 2 immunity, and highlight the increased complexity existing between the innate and adaptive arms of these responses. These additional steps in the type 2 immune pathway also offer potential targets for therapeutic intervention.. allergens| interleukin-25| interleukin-33| innate lymphoid cells| nuocytes| t helper type 2 cells| thymic stromal lymphopoietin| type 2 responses|thymic stromal lymphopoietin| inflammatory dendritic cells| dust-mite allergen| cd4(+) t-cells| cytokine-dependent immunity| human epithelial-cells| in-vitro development| nalp3 inflammasome| adaptive immunity| il-4 production.	DEC-2011	allergens| interleukin-25| interleukin-33| innate lymphoid cells| nuocytes| t helper type 2 cells| thymic stromal lymphopoietin| type 2 responses|thymic stromal lymphopoietin| inflammatory dendritic cells| dust-mite allergen| cd4(+) t-cells| cytokine-dependent immunity| human epithelial-cells| in-vitro development| nalp3 inflammasome| adaptive immunity| il-4 production	Oliphant, CJ; Barlow, JL; McKenzie, ANJ	Insights into the initiation of type 2 immune responses		IMMUNOLOGY	allergens; interleukin-25; interleukin-33; innate lymphoid cells; nuocytes; T helper type 2 cells; thymic stromal lymphopoietin; type 2 responses	THYMIC STROMAL LYMPHOPOIETIN; INFLAMMATORY DENDRITIC CELLS; DUST-MITE ALLERGEN; CD4(+) T-CELLS; CYTOKINE-DEPENDENT IMMUNITY; HUMAN EPITHELIAL-CELLS; IN-VITRO DEVELOPMENT; NALP3 INFLAMMASOME; ADAPTIVE IMMUNITY; IL-4 PRODUCTION	Type 2 immune responses, characterized by the differentiation of CD4(+) T helper type 2 (Th2) cells and the production of the type 2 cytokines interleukin-4 (IL-4), IL-5, IL-9 and IL-13, are associated with parasitic helminth infections and inflammatory conditions such as asthma and allergies. Until recently the initiating factors associated with type 2 responses had been poorly understood. This review addresses the recent advances in identifying the diverse range of antigens/allergens associated with type 2 responses and the function, expression and sources of type-2-initiating cytokines (thymic stromal lymphopoietin, IL-25 and IL-33). We also discuss the latest findings regarding innate lymphoid cells, such as nuocytes, as early sources of type 2 cytokines and their importance in protective immunity to helminth infections. These developments represent major breakthroughs in our understanding of type 2 immunity, and highlight the increased complexity existing between the innate and adaptive arms of these responses. These additional steps in the type 2 immune pathway also offer potential targets for therapeutic intervention.	81	73	2011	8	10.1111/j.1365-2567.2011.03499.x	Immunology
IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways. Rationale: IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. Objectives: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models; here we have investigated the effects of IL-9 blockade during chronic allergic inflammation. Methods: Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling. Measurements and Main Results: We found that IL-9 governs allergen-induced mast cell (MC) numbers in the lung and has pronounced effects on chronic allergic inflammation. Anti-IL-9 antibody-treated mice were protected from airway remodeling with a concomitant reduction in mature MC numbers and activation, in addition to decreased expression of the profibrotic mediators transforming growth factor-beta 1, vascular endothelial growth factor, and fibroblast growth factor-2 in the lung. Airway remodeling was associated with impaired lung function in the peripheral airways and this was reversed by IL-9 neutralization. In human asthmatic lung tissue, we identified MCs as the main IL-9 receptor expressing population and found them to be sources of vascular endothelial growth factor and fibroblast growth factor-2. Conclusions: Our data suggest an important role for an IL-9-MC axis in the pathology associated with chronic asthma and demonstrate that an impact on this axis could lead to a reduction in chronic inflammation and improved lung function in patients with asthma.. il-9| mast cells| asthma| airway remodeling| ahr|fibroblast-growth-factor| transgenic mice| pulmonary inflammation| smooth-muscle| interleukin 9| mild asthma| tgf-beta| hyperresponsiveness| challenge| expression.	APR 1-2011	il-9| mast cells| asthma| airway remodeling| ahr|fibroblast-growth-factor| transgenic mice| pulmonary inflammation| smooth-muscle| interleukin 9| mild asthma| tgf-beta| hyperresponsiveness| challenge| expression	Kearley, J; Erjefalt, JS; Andersson, C; Benjamin, E; Jones, CP; Robichaud, A; Pegorier, S; Brewah, Y; Burwell, TJ; Bjermer, L; Kiener, PA; Kolbec, R; Lloyd, CM; Coyle, AJ; Humbles, AA	IL-9 Governs Allergen-induced Mast Cell Numbers in the Lung and Chronic Remodeling of the Airways		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	IL-9; mast cells; asthma; airway remodeling; AHR	FIBROBLAST-GROWTH-FACTOR; TRANSGENIC MICE; PULMONARY INFLAMMATION; SMOOTH-MUSCLE; INTERLEUKIN 9; MILD ASTHMA; TGF-BETA; HYPERRESPONSIVENESS; CHALLENGE; EXPRESSION	Rationale: IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. Objectives: The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models; here we have investigated the effects of IL-9 blockade during chronic allergic inflammation. Methods: Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling. Measurements and Main Results: We found that IL-9 governs allergen-induced mast cell (MC) numbers in the lung and has pronounced effects on chronic allergic inflammation. Anti-IL-9 antibody-treated mice were protected from airway remodeling with a concomitant reduction in mature MC numbers and activation, in addition to decreased expression of the profibrotic mediators transforming growth factor-beta 1, vascular endothelial growth factor, and fibroblast growth factor-2 in the lung. Airway remodeling was associated with impaired lung function in the peripheral airways and this was reversed by IL-9 neutralization. In human asthmatic lung tissue, we identified MCs as the main IL-9 receptor expressing population and found them to be sources of vascular endothelial growth factor and fibroblast growth factor-2. Conclusions: Our data suggest an important role for an IL-9-MC axis in the pathology associated with chronic asthma and demonstrate that an impact on this axis could lead to a reduction in chronic inflammation and improved lung function in patients with asthma.	53	73	2011	11	10.1164/rccm.200909-1462OC	General & Internal Medicine; Respiratory System
The purinergic receptor P2Y(2) receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation. Background: Extracellular ATP contributes to the pathogenesis of asthma via signalling at purinergic receptors. However, the precise purinergic receptors subtypes mediating the pro-asthmatic effects of ATP have not been identified, yet. Methods: In vivo studies were performed using the OVA-alum model. Functional expression of the P2Y(2) purinergic receptor subtype on human monocyte-derived dendritic cells and eosinophils was investigated using real-time PCR, migration assays, and production of reactive oxygen species. Results: Compared to wild-type animals P2Y(2)-/- mice showed reduced allergic airway inflammation which can be explained by defective migration of blood myeloid DCs towards ATP in vitro and in vivo, whereas the influence of ATP on maturation and cytokine production was not changed. Additionally, ATP failed to induce migration of bone marrow-derived eosinophils from P2Y(2)R-deficient animals. The relevance of our findings for humans was confirmed in functional studies with human monocyte-derived DCs and eosinophils. Interestingly, stimulation of human DCs derived from allergic individuals with house dust mite allergen induced functional up-regulation of the P2Y(2)R subtype. Furthermore, eosinophils isolated from asthmatic individuals expressed higher levels of P2Y(2)R compared to healthy controls. This was of functional relevance as these eosinophils were more sensitive to ATP-induced migration and production of reactive oxygen metabolites. Conclusions: In summary, P2Y(2)R appears to be involved in asthmatic airway inflammation by mediating ATP-triggered migration of mDCs and eosinophils, as well as reactive oxygen species production. Together our data suggest that targeting P2Y(2)R might be a therapeutic option for the treatment of asthma.. asthma| atp| chemotaxis| dendritic cells| eosinophils|oxygen radical production| pharmacological characterization| nucleotide receptors| international union| tissue distribution| capacity| release| asthma| identification| expression.	DEC-2010	asthma| atp| chemotaxis| dendritic cells| eosinophils|oxygen radical production| pharmacological characterization| nucleotide receptors| international union| tissue distribution| capacity| release| asthma| identification| expression	Muller, T; Robaye, B; Vieira, RP; Ferrari, D; Grimm, M; Jakob, T; Martin, SF; Di Virgilio, F; Boeynaems, JM; Virchow, JC; Idzko, M	The purinergic receptor P2Y(2) receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation		ALLERGY	asthma; ATP; chemotaxis; dendritic cells; eosinophils	OXYGEN RADICAL PRODUCTION; PHARMACOLOGICAL CHARACTERIZATION; NUCLEOTIDE RECEPTORS; INTERNATIONAL UNION; TISSUE DISTRIBUTION; CAPACITY; RELEASE; ASTHMA; IDENTIFICATION; EXPRESSION	Background: Extracellular ATP contributes to the pathogenesis of asthma via signalling at purinergic receptors. However, the precise purinergic receptors subtypes mediating the pro-asthmatic effects of ATP have not been identified, yet. Methods: In vivo studies were performed using the OVA-alum model. Functional expression of the P2Y(2) purinergic receptor subtype on human monocyte-derived dendritic cells and eosinophils was investigated using real-time PCR, migration assays, and production of reactive oxygen species. Results: Compared to wild-type animals P2Y(2)-/- mice showed reduced allergic airway inflammation which can be explained by defective migration of blood myeloid DCs towards ATP in vitro and in vivo, whereas the influence of ATP on maturation and cytokine production was not changed. Additionally, ATP failed to induce migration of bone marrow-derived eosinophils from P2Y(2)R-deficient animals. The relevance of our findings for humans was confirmed in functional studies with human monocyte-derived DCs and eosinophils. Interestingly, stimulation of human DCs derived from allergic individuals with house dust mite allergen induced functional up-regulation of the P2Y(2)R subtype. Furthermore, eosinophils isolated from asthmatic individuals expressed higher levels of P2Y(2)R compared to healthy controls. This was of functional relevance as these eosinophils were more sensitive to ATP-induced migration and production of reactive oxygen metabolites. Conclusions: In summary, P2Y(2)R appears to be involved in asthmatic airway inflammation by mediating ATP-triggered migration of mDCs and eosinophils, as well as reactive oxygen species production. Together our data suggest that targeting P2Y(2)R might be a therapeutic option for the treatment of asthma.	27	73	2010	9	10.1111/j.1398-9995.2010.02426.x	Allergy; Immunology
Clinical Effects of Home Telemonitoring in the Context of Diabetes, Asthma, Heart Failure and Hypertension: A Systematic Review. Background: Home telemonitoring figures among the various solutions that could help attenuate some of the problems associated with aging populations, rates of chronic illness, and shortages of health professionals. Objective: The primary aim of this study was to further our understanding of the clinical effects associated with home telemonitoring programs in the context of chronic diseases. Methods: We conducted a systematic review which covered studies published between January 1966 and December 2008. MEDLINE, The Cochrane Library, and the INAHTA (International Network of Agencies for Health Technology Assessment) database were consulted. Our inclusion criteria consisted of: (I) English language publications in peer-reviewed journals or conference proceedings and (2) studies involving patients with diabetes, asthma, heart failure, or hypertension, and presenting results on the clinical effects of home telemonitoring. Results: In all, 62 empirical studies were analyzed. The results from studies involving patients with diabetes indicated a trend toward patients with home telemonitoring achieving better glycemic control. In most trials in which patients with asthma were enrolled, results showed significant improvements in patients' peak expiratory flows, significant reductions in the symptoms associated with this illness, and improvements in perceived quality of life. Virtually all studies involving patients with hypertension demonstrated the ability of home telemonitoring to reduce systolic and/or diastolic blood pressure. Lastly, due to the equivocal nature of current findings of home telemonitoring involving patients with heart failure, larger trials are still needed to confirm the clinical effects of this technology for these patients. Conclusions: Although home telemonitoring appears to be a promising approach to patient management, designers of future studies should consider ways to make this technology more effective as well as controlling possible mediating variables.. home telemonitoring| information technology| chronic illnesses| clinical effects|randomized controlled-trial| blood-pressure control| urban african-americans| monitoring-system| glycemic control| follow-up| high-risk| management| telemedicine| care.	APR-JUN-2010	home telemonitoring| information technology| chronic illnesses| clinical effects|randomized controlled-trial| blood-pressure control| urban african-americans| monitoring-system| glycemic control| follow-up| high-risk| management| telemedicine| care	Pare, G; Moqadem, K; Pineau, G; St-Hilaire, C	Clinical Effects of Home Telemonitoring in the Context of Diabetes, Asthma, Heart Failure and Hypertension: A Systematic Review		JOURNAL OF MEDICAL INTERNET RESEARCH	Home telemonitoring; information technology; chronic illnesses; clinical effects	RANDOMIZED CONTROLLED-TRIAL; BLOOD-PRESSURE CONTROL; URBAN AFRICAN-AMERICANS; MONITORING-SYSTEM; GLYCEMIC CONTROL; FOLLOW-UP; HIGH-RISK; MANAGEMENT; TELEMEDICINE; CARE	Background: Home telemonitoring figures among the various solutions that could help attenuate some of the problems associated with aging populations, rates of chronic illness, and shortages of health professionals. Objective: The primary aim of this study was to further our understanding of the clinical effects associated with home telemonitoring programs in the context of chronic diseases. Methods: We conducted a systematic review which covered studies published between January 1966 and December 2008. MEDLINE, The Cochrane Library, and the INAHTA (International Network of Agencies for Health Technology Assessment) database were consulted. Our inclusion criteria consisted of: (I) English language publications in peer-reviewed journals or conference proceedings and (2) studies involving patients with diabetes, asthma, heart failure, or hypertension, and presenting results on the clinical effects of home telemonitoring. Results: In all, 62 empirical studies were analyzed. The results from studies involving patients with diabetes indicated a trend toward patients with home telemonitoring achieving better glycemic control. In most trials in which patients with asthma were enrolled, results showed significant improvements in patients' peak expiratory flows, significant reductions in the symptoms associated with this illness, and improvements in perceived quality of life. Virtually all studies involving patients with hypertension demonstrated the ability of home telemonitoring to reduce systolic and/or diastolic blood pressure. Lastly, due to the equivocal nature of current findings of home telemonitoring involving patients with heart failure, larger trials are still needed to confirm the clinical effects of this technology for these patients. Conclusions: Although home telemonitoring appears to be a promising approach to patient management, designers of future studies should consider ways to make this technology more effective as well as controlling possible mediating variables.	86	73	2010	15	10.2196/jmir.1357	Health Care Sciences & Services; Medical Informatics
Personal and ambient air pollution exposures and lung function decrements in children with asthma. BACKGROUND: Epidemiologic studies have shown associations between asthma outcomes and outdoor air pollutants such as nitrogen dioxide and particulate matter mass < 2.5 mu m in diameter (PM2.5). Independent effects of specific pollutants have been difficult to detect because most studies have relied on highly correlated central-site measurements. OBJECTIVES: This study was designed to evaluate the relationship of daily changes in percent-predicted forced expiratory volume in 1 see (FEV1) with personal and ambient air pollutant exposures. METHODS: For 10 days each, we followed 53 subjects with asthma who were 9-18 years of age and living in the Los Angeles, California, air basin. Subjects self-administered home spirometry in the morning, afternoon, and evening. We measured personal hourly PM2.5 mass, 24-hr PM2.5 elemental and organic carbon (EC-OC), and 24-hr NO2, and the same 24-hr average outdoor central-site (ambient) exposures. We analyzed data with transitional mixed models controlling for personal temperature and humidity, and as-needed beta(2)-agonist inhaler use. RESULTS: FEV1 decrements were significantly associated with increasing hourly peak and daily average personal PM2.5, but not ambient PM2.5. Personal NO2 was also inversely associated with FEV1. Ambient NO2 was more weakly associated. We found stronger associations among 37 subjects not taking controller bronchodilators as follows: Personal EC-OC was inversely associated with morning FEV1; for an interquartile increase of 71 mu g/m(3) 1-hr maximum personal PM2.5, overall percent-predicted FEV1 decreased by 1.32% [95% confidence interval (CI), -2.00 to -0.65%]; and for an interquartile increase of 16.8 ppb 2-day average personal NO2, overall percent-predicted FLV1 decreased by 2.45% (95% CI, -3.57 to -1.33%). Associations of both personal PM2.5 and NO2 with FEV1 remained when co-regressed, and both confounded ambient NO2. CONCLUSIONS: Independent pollutant associations with lung function might be missed using ambient data alone. Different sets of causal components are suggested by independence of FEV1 associations with personal PM2.5 mass from associations with personal NO2.. asthma| epidemiology| forced expiratory flow rates| longitudinal data analysis| nitrogen dioxide| panel study| particulate air pollution|antiinflammatory medication use| nitrogen-dioxide exposure| peak expiratory flow| particulate air| ultrafine particles| pollutants| symptoms| health| association| mass.	APR-2008	asthma| epidemiology| forced expiratory flow rates| longitudinal data analysis| nitrogen dioxide| panel study| particulate air pollution|antiinflammatory medication use| nitrogen-dioxide exposure| peak expiratory flow| particulate air| ultrafine particles| pollutants| symptoms| health| association| mass	Delfino, RJ; Staimer, N; Tjoa, T; Gillen, D; Kleinman, MT; Sioutas, C; Cooper, D	Personal and ambient air pollution exposures and lung function decrements in children with asthma		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; epidemiology; forced expiratory flow rates; longitudinal data analysis; nitrogen dioxide; panel study; particulate air pollution	ANTIINFLAMMATORY MEDICATION USE; NITROGEN-DIOXIDE EXPOSURE; PEAK EXPIRATORY FLOW; PARTICULATE AIR; ULTRAFINE PARTICLES; POLLUTANTS; SYMPTOMS; HEALTH; ASSOCIATION; MASS	BACKGROUND: Epidemiologic studies have shown associations between asthma outcomes and outdoor air pollutants such as nitrogen dioxide and particulate matter mass < 2.5 mu m in diameter (PM2.5). Independent effects of specific pollutants have been difficult to detect because most studies have relied on highly correlated central-site measurements. OBJECTIVES: This study was designed to evaluate the relationship of daily changes in percent-predicted forced expiratory volume in 1 see (FEV1) with personal and ambient air pollutant exposures. METHODS: For 10 days each, we followed 53 subjects with asthma who were 9-18 years of age and living in the Los Angeles, California, air basin. Subjects self-administered home spirometry in the morning, afternoon, and evening. We measured personal hourly PM2.5 mass, 24-hr PM2.5 elemental and organic carbon (EC-OC), and 24-hr NO2, and the same 24-hr average outdoor central-site (ambient) exposures. We analyzed data with transitional mixed models controlling for personal temperature and humidity, and as-needed beta(2)-agonist inhaler use. RESULTS: FEV1 decrements were significantly associated with increasing hourly peak and daily average personal PM2.5, but not ambient PM2.5. Personal NO2 was also inversely associated with FEV1. Ambient NO2 was more weakly associated. We found stronger associations among 37 subjects not taking controller bronchodilators as follows: Personal EC-OC was inversely associated with morning FEV1; for an interquartile increase of 71 mu g/m(3) 1-hr maximum personal PM2.5, overall percent-predicted FEV1 decreased by 1.32% [95% confidence interval (CI), -2.00 to -0.65%]; and for an interquartile increase of 16.8 ppb 2-day average personal NO2, overall percent-predicted FLV1 decreased by 2.45% (95% CI, -3.57 to -1.33%). Associations of both personal PM2.5 and NO2 with FEV1 remained when co-regressed, and both confounded ambient NO2. CONCLUSIONS: Independent pollutant associations with lung function might be missed using ambient data alone. Different sets of causal components are suggested by independence of FEV1 associations with personal PM2.5 mass from associations with personal NO2.	46	73	2008	9		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Exhaled nitric oxide concentration is affected by age, height, and race in healthy 9-to 12-year-old children. Background: The fractional concentration of exhaled nitric oxide (FENO) is a useful indicator of airway inflammation in children and adults with asthma. Methods: We determined the range of FENO concentrations and the factors affecting it in a large sample of healthy school children attending grades 4 through 6, in Windsor, ON, Canada. Results: FENO was measured in 657 children between 9.1 and 12.9 years of age. The range of FENO concentrations in healthy school children was 12.7 parts per billion (ppb) [95% confidence interval (0), 11.8 to 13.7 ppb] in whites and 22.8 ppb [95% CI, 17.9 to 27.7 ppb] in Asian-Canadian children (p < 0.001). FENO values also appeared to be higher in African-Canadian children than in whites, although the CI was wide because of the small number of African-Canadian children sampled. FENO rose slightly but significantly with age (p = 0.007) and with height (p = 0.023). Body mass index and gender did not significantly alter the measured FENO. FVC had a nonsignificant effect on FENO. Participation in physical activity during the same day had a borderline-significant effect on measured FENO, but a reported history of a respiratory tract infection in the preceding 2 weeks did not. Conclusions: FENO concentrations in healthy school-aged children appeared to be affected by race, and, to a lesser extent, by age and height. These factors should be taken into consideration when interpreting clinical results.. asian continental ancestry group| asthma| breath tests| child| continental population groups| growth| nitric oxide| reference values|body-mass index| chinese children| reference values| school-age| asthma| air| schoolchildren| adolescents| marker.	JAN-2008	asian continental ancestry group| asthma| breath tests| child| continental population groups| growth| nitric oxide| reference values|body-mass index| chinese children| reference values| school-age| asthma| air| schoolchildren| adolescents| marker	Kovesi, T; Kulka, R; Dales, R	Exhaled nitric oxide concentration is affected by age, height, and race in healthy 9-to 12-year-old children		CHEST	Asian continental ancestry group; asthma; breath tests; child; continental population groups; growth; nitric oxide; reference values	BODY-MASS INDEX; CHINESE CHILDREN; REFERENCE VALUES; SCHOOL-AGE; ASTHMA; AIR; SCHOOLCHILDREN; ADOLESCENTS; MARKER	Background: The fractional concentration of exhaled nitric oxide (FENO) is a useful indicator of airway inflammation in children and adults with asthma. Methods: We determined the range of FENO concentrations and the factors affecting it in a large sample of healthy school children attending grades 4 through 6, in Windsor, ON, Canada. Results: FENO was measured in 657 children between 9.1 and 12.9 years of age. The range of FENO concentrations in healthy school children was 12.7 parts per billion (ppb) [95% confidence interval (0), 11.8 to 13.7 ppb] in whites and 22.8 ppb [95% CI, 17.9 to 27.7 ppb] in Asian-Canadian children (p < 0.001). FENO values also appeared to be higher in African-Canadian children than in whites, although the CI was wide because of the small number of African-Canadian children sampled. FENO rose slightly but significantly with age (p = 0.007) and with height (p = 0.023). Body mass index and gender did not significantly alter the measured FENO. FVC had a nonsignificant effect on FENO. Participation in physical activity during the same day had a borderline-significant effect on measured FENO, but a reported history of a respiratory tract infection in the preceding 2 weeks did not. Conclusions: FENO concentrations in healthy school-aged children appeared to be affected by race, and, to a lesser extent, by age and height. These factors should be taken into consideration when interpreting clinical results.	30	73	2008	7	10.1378/chest.07-1177	General & Internal Medicine; Respiratory System
Outdoor air pollution and emergency department visits for asthma among children and adults: A case-crossover study in northern Alberta, Canada. Background: Recent studies have observed positive associations between outdoor air pollution and emergency department (ED) visits for asthma. However, few have examined the possible confounding influence of aeroallergens, or reported findings among very young children. Methods: A time stratified case-crossover design was used to examine 57,912 ED asthma visits among individuals two years of age and older in the census metropolitan area of Edmonton, Canada between April 1, 1992 and March 31, 2002. Daily air pollution levels for the entire region were estimated from three fixed-site monitoring stations. Similarly, daily levels of aeroallergens were estimated using rotational impaction sampling methods for the period between 1996 and 2002. Odds ratios and their corresponding 95% confidence intervals were estimated using conditional logistic regression with adjustment for temperature, relative humidity and seasonal epidemics of viral related respiratory disease. Results: Positive associations for asthma visits with outdoor air pollution levels were observed between April and September, but were absent during the remainder of the year. Effects were strongest among young children. Namely, an increase in the interquartile range of the 5-day average for NO(2) and CO levels between April and September was associated with a 50% and 48% increase, respectively, in the number of ED visits among children 2-4 years of age (p < 0.05). Strong associations were also observed with these pollutants among those 75 years of age and older. Ozone and particulate matter were also associated with asthma visits. Air pollution risk estimates were largely unchanged after adjustment for aeroallergen levels. Conclusion: Our findings, taken together, suggest that exposure to ambient levels of air pollution is an important determinant of ED visits for asthma, particularly among young children and the elderly.. southern california children| respiratory hospital admissions| lung-function growth| childhood asthma| room visits| nitrogen-dioxide| time-series| saint-john| association| ozone.	DEC 24-2007	southern california children| respiratory hospital admissions| lung-function growth| childhood asthma| room visits| nitrogen-dioxide| time-series| saint-john| association| ozone	Villeneuve, PJ; Chen, L; Rowe, BH; Coates, F	Outdoor air pollution and emergency department visits for asthma among children and adults: A case-crossover study in northern Alberta, Canada		ENVIRONMENTAL HEALTH		SOUTHERN CALIFORNIA CHILDREN; RESPIRATORY HOSPITAL ADMISSIONS; LUNG-FUNCTION GROWTH; CHILDHOOD ASTHMA; ROOM VISITS; NITROGEN-DIOXIDE; TIME-SERIES; SAINT-JOHN; ASSOCIATION; OZONE	Background: Recent studies have observed positive associations between outdoor air pollution and emergency department (ED) visits for asthma. However, few have examined the possible confounding influence of aeroallergens, or reported findings among very young children. Methods: A time stratified case-crossover design was used to examine 57,912 ED asthma visits among individuals two years of age and older in the census metropolitan area of Edmonton, Canada between April 1, 1992 and March 31, 2002. Daily air pollution levels for the entire region were estimated from three fixed-site monitoring stations. Similarly, daily levels of aeroallergens were estimated using rotational impaction sampling methods for the period between 1996 and 2002. Odds ratios and their corresponding 95% confidence intervals were estimated using conditional logistic regression with adjustment for temperature, relative humidity and seasonal epidemics of viral related respiratory disease. Results: Positive associations for asthma visits with outdoor air pollution levels were observed between April and September, but were absent during the remainder of the year. Effects were strongest among young children. Namely, an increase in the interquartile range of the 5-day average for NO(2) and CO levels between April and September was associated with a 50% and 48% increase, respectively, in the number of ED visits among children 2-4 years of age (p < 0.05). Strong associations were also observed with these pollutants among those 75 years of age and older. Ozone and particulate matter were also associated with asthma visits. Air pollution risk estimates were largely unchanged after adjustment for aeroallergen levels. Conclusion: Our findings, taken together, suggest that exposure to ambient levels of air pollution is an important determinant of ED visits for asthma, particularly among young children and the elderly.	70	73	2007	15	10.1186/1476-069X-6-40	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Critical link between TRAIL and CCL20 for the activation of T(H)2 cells and the expression of allergic airway disease. The role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in immune responses mediated by T-helper 2 (T(H)2) lymphocytes is unknown. Here we characterize the development of allergic airway disease in TRAIL-deficient (Tnfsf10(-/-)) mice and in mice exposed to short interfering RNA targeting TRAIL. We show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways. Attenuated homing limits TH2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6. Activation of STAT6 by interleukin-13 restores airway hyperreactivity in Tnfsf10(-/-) mice. Recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells. TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma.. apoptosis-inducing ligand| dendritic cells| in-vivo| experimental asthma| tumor-metastasis| inhaled antigen| atopic asthma| hyperreactivity| inflammation| il-13.	NOV-2007	apoptosis-inducing ligand| dendritic cells| in-vivo| experimental asthma| tumor-metastasis| inhaled antigen| atopic asthma| hyperreactivity| inflammation| il-13	Weckmann, M; Collison, A; Simpson, JL; Kopp, MV; Wark, PAB; Smyth, MJ; Yagita, H; Matthaei, KI; Hansbro, N; Whitehead, B; Gibson, PG; Foster, PS; Mattes, J	Critical link between TRAIL and CCL20 for the activation of T(H)2 cells and the expression of allergic airway disease		NATURE MEDICINE		APOPTOSIS-INDUCING LIGAND; DENDRITIC CELLS; IN-VIVO; EXPERIMENTAL ASTHMA; TUMOR-METASTASIS; INHALED ANTIGEN; ATOPIC ASTHMA; HYPERREACTIVITY; INFLAMMATION; IL-13	The role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in immune responses mediated by T-helper 2 (T(H)2) lymphocytes is unknown. Here we characterize the development of allergic airway disease in TRAIL-deficient (Tnfsf10(-/-)) mice and in mice exposed to short interfering RNA targeting TRAIL. We show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways. Attenuated homing limits TH2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6. Activation of STAT6 by interleukin-13 restores airway hyperreactivity in Tnfsf10(-/-) mice. Recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells. TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma.	50	73	2007	8	10.1038/nm1660	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Fragrance ingredient labelling in products on sale in the UK. Background The seventh amendment of the European Union (EU) Cosmetics Directive (March 2005) and the Detergents Regulations of the EU (October 2005) are now legal requirements in Europe. Cosmetic products and detergents must be labelled for 26 individual named fragrances, when present at concentrations of > 10 parts per million (p.p.m.) in leave-on products and > 100 p.p.m. in rinse-off products. Objectives To make an assessment of the exposure pattern to fragrance of the U.K. consumer and to determine the frequency with which the constituent fragrances of fragrance mix I (FM I) and fragrance mix II (FM II) are included in products currently sold in the U.K. Methods A study of perfumed cosmetic and household products available on the shelves of U.K. retailers was carried out in January 2006. Products were included if 'parfum' or 'aroma' was listed among the ingredients. Three hundred products were surveyed and any of the 26 listed fragrances named on the label were recorded. Results The top six most frequently labelled fragrances were linalool (190; 63%), limonene (189; 63%), citronellol (145; 48%), geraniol (126; 42%), butyl phenyl methyl propional (Lilial((TM))) (126; 42%) and hexyl cinnamal (125; (42%). One of these, geraniol, is present in FM I and two others, citronellol and hexyl cinnamal, in FM II, thus tested as part of the British Standard patch test series. The frequencies of other constituents of FM I were as follows: eugenol, 80 (27%); hydroxycitronellal, 52 (17%); isoeugenol, 27 (9%); cinnamic alcohol, 25 (8%); amyl cinnamal, 22 (7%); cinnamal, 17 (6%); Evernia prunastri (oak moss absolute), 13 (4%). The other constituents of FM II occurred as follows: coumarin, 90 (30%); hydroxyisohexyl-3-cyclohexene carboxaldehyde (Lyral((TM))), 88 (29%); citral, 74 (25%); farnesol, 23 (8%). Linalool (n = 46; 66%) was the most frequently found fragrance in 70 personal care products (soap, shampoo, shower gel). Linalool (n = 47; 80%) and limonene (n = 45; 76%) were the most frequent in 59 products for men (e.g. aftershave). Limonene (n = 29; 51%) predominated in 57 household products (washing-up liquid, detergent). Limonene (n = 43; 98%) and linalool (n = 42; 95%) were the most frequent fragrances in 44 perfumes for women. Alpha-isomethyl ionone (n = 28; 72%) was the most frequent in 39 cosmetics (foundation, lipstick, etc). Citronellol predominated (n = 15; 88%) in 17 deodorants and limonene (n = 9; 64%) was the commonest in 14 dental products (toothpaste and mouthwash). Thirty-four products (11%) contained none of the listed fragrances but were labelled as containing 'parfum' or 'aroma'. Conclusions There is ongoing consumer exposure to the most frequent sensitizers in FM I: E. prunastri, isoeugenol and the cinnamon fragrances cinnamal and cinnamic alcohol. Hydroxyisohexyl-3-cyclohexene carboxaldehyde (Lyral((TM))) is present at significant concentrations in almost one-third of products. Linalool and limonene, fragrance terpenes which are significant allergens in their oxidized state, are the most frequent fragrances encountered by individuals living in the U.K. The current exposure pattern of the U.K. consumer suggests that we should add oxidized limonene and oxidized linalool to the test series for patients suspected to have fragrance allergy.. allergic contact dermatitis| consumer products| fragrance| labelling| limonene| linalool|patch-test population| allergy| perfumes| chloroatranol| sensitization| linalool| lyral(r)| mix.	AUG-2007	allergic contact dermatitis| consumer products| fragrance| labelling| limonene| linalool|patch-test population| allergy| perfumes| chloroatranol| sensitization| linalool| lyral(r)| mix	Buckley, DA	Fragrance ingredient labelling in products on sale in the UK		BRITISH JOURNAL OF DERMATOLOGY	allergic contact dermatitis; consumer products; fragrance; labelling; limonene; linalool	PATCH-TEST POPULATION; ALLERGY; PERFUMES; CHLOROATRANOL; SENSITIZATION; LINALOOL; LYRAL(R); MIX	Background The seventh amendment of the European Union (EU) Cosmetics Directive (March 2005) and the Detergents Regulations of the EU (October 2005) are now legal requirements in Europe. Cosmetic products and detergents must be labelled for 26 individual named fragrances, when present at concentrations of > 10 parts per million (p.p.m.) in leave-on products and > 100 p.p.m. in rinse-off products. Objectives To make an assessment of the exposure pattern to fragrance of the U.K. consumer and to determine the frequency with which the constituent fragrances of fragrance mix I (FM I) and fragrance mix II (FM II) are included in products currently sold in the U.K. Methods A study of perfumed cosmetic and household products available on the shelves of U.K. retailers was carried out in January 2006. Products were included if 'parfum' or 'aroma' was listed among the ingredients. Three hundred products were surveyed and any of the 26 listed fragrances named on the label were recorded. Results The top six most frequently labelled fragrances were linalool (190; 63%), limonene (189; 63%), citronellol (145; 48%), geraniol (126; 42%), butyl phenyl methyl propional (Lilial((TM))) (126; 42%) and hexyl cinnamal (125; (42%). One of these, geraniol, is present in FM I and two others, citronellol and hexyl cinnamal, in FM II, thus tested as part of the British Standard patch test series. The frequencies of other constituents of FM I were as follows: eugenol, 80 (27%); hydroxycitronellal, 52 (17%); isoeugenol, 27 (9%); cinnamic alcohol, 25 (8%); amyl cinnamal, 22 (7%); cinnamal, 17 (6%); Evernia prunastri (oak moss absolute), 13 (4%). The other constituents of FM II occurred as follows: coumarin, 90 (30%); hydroxyisohexyl-3-cyclohexene carboxaldehyde (Lyral((TM))), 88 (29%); citral, 74 (25%); farnesol, 23 (8%). Linalool (n = 46; 66%) was the most frequently found fragrance in 70 personal care products (soap, shampoo, shower gel). Linalool (n = 47; 80%) and limonene (n = 45; 76%) were the most frequent in 59 products for men (e.g. aftershave). Limonene (n = 29; 51%) predominated in 57 household products (washing-up liquid, detergent). Limonene (n = 43; 98%) and linalool (n = 42; 95%) were the most frequent fragrances in 44 perfumes for women. Alpha-isomethyl ionone (n = 28; 72%) was the most frequent in 39 cosmetics (foundation, lipstick, etc). Citronellol predominated (n = 15; 88%) in 17 deodorants and limonene (n = 9; 64%) was the commonest in 14 dental products (toothpaste and mouthwash). Thirty-four products (11%) contained none of the listed fragrances but were labelled as containing 'parfum' or 'aroma'. Conclusions There is ongoing consumer exposure to the most frequent sensitizers in FM I: E. prunastri, isoeugenol and the cinnamon fragrances cinnamal and cinnamic alcohol. Hydroxyisohexyl-3-cyclohexene carboxaldehyde (Lyral((TM))) is present at significant concentrations in almost one-third of products. Linalool and limonene, fragrance terpenes which are significant allergens in their oxidized state, are the most frequent fragrances encountered by individuals living in the U.K. The current exposure pattern of the U.K. consumer suggests that we should add oxidized limonene and oxidized linalool to the test series for patients suspected to have fragrance allergy.	23	73	2007	6	10.1111/j.1365-2133.2007.08018.x	Dermatology
COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1. Cyclooxygenase-2 (COX-2) plays an important role in the inflammatory response induced by physiologic and stress stimuli. Exposure to diesel exhaust particulate matter (DEP) has been shown to induce pulmonary inflammation and exacerbate asthma and chronic obstructive pulmonary disease. DEP is a potent inducer of inflammatory reponses in human airway epithelial cells. The mechanism through which DEP inhalation induces inflammatory mediator expression is not understood. In this report, we demonstrate that DEP can induce the expression of COX-2 gene in a human bronchial epithelial cell line (BEAS-2B) at both transcriptional and protein levels. The induction of COX-2 gene expression involves chromatin modification, in particular acetylation and deacetylation of histones. We show that exposure to DEP increases the acetylation of histone H4 associated with the COX-2 promoter and causes degradation of histone deacetylase 1 (HDAC1). Further, we establish that HDAC1 plays a pivotal role in mediating the transcriptional activation of the COX-2 gene in BEAS-2B cells exposed to DEP, supported by evidence that the down-regulation of HDAC1 using siRNA leads to activation of COX-2 gene expression, whereas overexpression of HDAC1 results in its repression. Finally, DEP exposure induced recruitment of histone acetyltransferase (HAT) p300 to the promoter of the COX-2 gene, suggesting that acetylation is also important in regulating its expression in response to DEP exposure. These results show for the first time acetylation via selective degradation of HDAC1, and that recruitment of HAT plays an important role in DEP-induced expression of the COX-2 gene.. diesel exhaust particles| cox-2| hdac| airway epithelial cells|bronchial epithelial-cells| cyclooxygenase-2 promoter activation| endoperoxide synthase-2 gene| exhaust particles| histone deacetylase-1| regulating cyclooxygenase-2| transcriptional activation| inflammatory mediators| oxidative stress| response element.	AUG-2007	diesel exhaust particles| cox-2| hdac| airway epithelial cells|bronchial epithelial-cells| cyclooxygenase-2 promoter activation| endoperoxide synthase-2 gene| exhaust particles| histone deacetylase-1| regulating cyclooxygenase-2| transcriptional activation| inflammatory mediators| oxidative stress| response element	Cao, DS; Bromberg, PA; Samet, JM	COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	diesel exhaust particles; COX-2; HDAC; airway epithelial cells	BRONCHIAL EPITHELIAL-CELLS; CYCLOOXYGENASE-2 PROMOTER ACTIVATION; ENDOPEROXIDE SYNTHASE-2 GENE; EXHAUST PARTICLES; HISTONE DEACETYLASE-1; REGULATING CYCLOOXYGENASE-2; TRANSCRIPTIONAL ACTIVATION; INFLAMMATORY MEDIATORS; OXIDATIVE STRESS; RESPONSE ELEMENT	Cyclooxygenase-2 (COX-2) plays an important role in the inflammatory response induced by physiologic and stress stimuli. Exposure to diesel exhaust particulate matter (DEP) has been shown to induce pulmonary inflammation and exacerbate asthma and chronic obstructive pulmonary disease. DEP is a potent inducer of inflammatory reponses in human airway epithelial cells. The mechanism through which DEP inhalation induces inflammatory mediator expression is not understood. In this report, we demonstrate that DEP can induce the expression of COX-2 gene in a human bronchial epithelial cell line (BEAS-2B) at both transcriptional and protein levels. The induction of COX-2 gene expression involves chromatin modification, in particular acetylation and deacetylation of histones. We show that exposure to DEP increases the acetylation of histone H4 associated with the COX-2 promoter and causes degradation of histone deacetylase 1 (HDAC1). Further, we establish that HDAC1 plays a pivotal role in mediating the transcriptional activation of the COX-2 gene in BEAS-2B cells exposed to DEP, supported by evidence that the down-regulation of HDAC1 using siRNA leads to activation of COX-2 gene expression, whereas overexpression of HDAC1 results in its repression. Finally, DEP exposure induced recruitment of histone acetyltransferase (HAT) p300 to the promoter of the COX-2 gene, suggesting that acetylation is also important in regulating its expression in response to DEP exposure. These results show for the first time acetylation via selective degradation of HDAC1, and that recruitment of HAT plays an important role in DEP-induced expression of the COX-2 gene.	50	73	2007	8	10.1165/rcmb.2006-0449OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
"Development of an environmental relative moldiness index for US homes. Objective: The objective of this study, was to establish a national relative moldiness index for homes in the United States. Methods: As part of the Housing and Urban Development's American Healthy Homes Survey, dust samples were collected by vacuuming 2 m(2) in the bedrooms plus 2 m(2) in the living rooms from a nationally, representative 1096 homes in the United States using the Mitest sampler. Five milligrams of sieved (300 mu m pore, nylon mesh) dust was analyzed by mold-specific quantitative polymerase chain reaction for the 36 indicator species in 1096 samples. Results: On the basis of this standardized national sampling and analysis, an ""Environmental Relative Moldiness Index"" was created with values ranging from about -10 to 20 or above (lowest to highest). vi Conclusions: The Environmental Relative Moldiness Index scale may be useful for home mold-burden estimates in epidemiological studies.. quantitative pcr analysis| airborne fungi| outdoor air| asthma| propagules| buildings| dustborne| children| water| dust."	AUG-2007	quantitative pcr analysis| airborne fungi| outdoor air| asthma| propagules| buildings| dustborne| children| water| dust	Vesper, S; McKinstry, C; Haugland, R; Wymer, L; Bradham, K; Ashley, P; Cox, D; Dewalt, G; Friedman, W	Development of an environmental relative moldiness index for US homes		JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		QUANTITATIVE PCR ANALYSIS; AIRBORNE FUNGI; OUTDOOR AIR; ASTHMA; PROPAGULES; BUILDINGS; DUSTBORNE; CHILDREN; WATER; DUST	"Objective: The objective of this study, was to establish a national relative moldiness index for homes in the United States. Methods: As part of the Housing and Urban Development's American Healthy Homes Survey, dust samples were collected by vacuuming 2 m(2) in the bedrooms plus 2 m(2) in the living rooms from a nationally, representative 1096 homes in the United States using the Mitest sampler. Five milligrams of sieved (300 mu m pore, nylon mesh) dust was analyzed by mold-specific quantitative polymerase chain reaction for the 36 indicator species in 1096 samples. Results: On the basis of this standardized national sampling and analysis, an ""Environmental Relative Moldiness Index"" was created with values ranging from about -10 to 20 or above (lowest to highest). vi Conclusions: The Environmental Relative Moldiness Index scale may be useful for home mold-burden estimates in epidemiological studies."	19	73	2007	5	10.1097/JOM.0b013e3181255e98	Public, Environmental & Occupational Health
Sensitization to Ascaris lumbricoides and severity of childhood asthma in Costa Rica. Background: Little is known about sensitization (defined as a positive IgE) to helminths and disease severity in patients with asthma. Objectives: To examine the relationship between sensitization (defined as a positive IgE) to Ascaris lumbricoides and measures of asthma morbidity and severity in a Costa Rican population with low prevalence of parasitic infection but high prevalence of parasitic exposure. Methods: Cross-sectional study of 439 children (ages 6 to 14 years) with asthma. Linear regression and logistic regression were used for the multivariate statistical analysis. Results: After adjustment for parental education and other covariates, sensitization to Ascaris lumbricoides was associated with having at least 1 positive skin test to allergens (odds ratio, 5.15; 95% CI, 2.36-11.21; P < .001), increased total serum IgE and eosinophils in peripheral blood, reductions in FEV1 and FEV1/forced vital capacity, increased airway responsiveness and bronchodilator responsiveness, and hospitalizations for asthma in the previous year (odds ratio, 3.08; 95% Cl, 1.23-7.68; P = .02). Conclusion: Sensitization to Ascaris lumbricoides is associated with increased severity and morbidity of asthma among children in Costa Rica. This association is likely mediated by an increased degree of atopy among children with asthma who are sensitized to Asearis. Clinical implications: In areas with a low prevalence of helminthiasis such as Costa Rica, Ascaris sensitization may be an important marker of severe atopy and disease morbidity in children with asthma.. ascaris| helminth| atopy| exacerbation| severity| asthma| costa rica|immunoglobulin-e| geohelminth infections| allergic sensitization| anthelmintic treatment| ige antibodies| rural area| children| atopy| reactivity| parasites.	MAR-2007	ascaris| helminth| atopy| exacerbation| severity| asthma| costa rica|immunoglobulin-e| geohelminth infections| allergic sensitization| anthelmintic treatment| ige antibodies| rural area| children| atopy| reactivity| parasites	Hunninghake, GM; Soto-Quiros, ME; Avila, L; Ly, NP; Liang, C; Sylvia, JS; Klanderman, BJ; Silverman, EK; Celedon, JC	Sensitization to Ascaris lumbricoides and severity of childhood asthma in Costa Rica		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Ascaris; helminth; atopy; exacerbation; severity; asthma; Costa Rica	IMMUNOGLOBULIN-E; GEOHELMINTH INFECTIONS; ALLERGIC SENSITIZATION; ANTHELMINTIC TREATMENT; IGE ANTIBODIES; RURAL AREA; CHILDREN; ATOPY; REACTIVITY; PARASITES	Background: Little is known about sensitization (defined as a positive IgE) to helminths and disease severity in patients with asthma. Objectives: To examine the relationship between sensitization (defined as a positive IgE) to Ascaris lumbricoides and measures of asthma morbidity and severity in a Costa Rican population with low prevalence of parasitic infection but high prevalence of parasitic exposure. Methods: Cross-sectional study of 439 children (ages 6 to 14 years) with asthma. Linear regression and logistic regression were used for the multivariate statistical analysis. Results: After adjustment for parental education and other covariates, sensitization to Ascaris lumbricoides was associated with having at least 1 positive skin test to allergens (odds ratio, 5.15; 95% CI, 2.36-11.21; P < .001), increased total serum IgE and eosinophils in peripheral blood, reductions in FEV1 and FEV1/forced vital capacity, increased airway responsiveness and bronchodilator responsiveness, and hospitalizations for asthma in the previous year (odds ratio, 3.08; 95% Cl, 1.23-7.68; P = .02). Conclusion: Sensitization to Ascaris lumbricoides is associated with increased severity and morbidity of asthma among children in Costa Rica. This association is likely mediated by an increased degree of atopy among children with asthma who are sensitized to Asearis. Clinical implications: In areas with a low prevalence of helminthiasis such as Costa Rica, Ascaris sensitization may be an important marker of severe atopy and disease morbidity in children with asthma.	41	73	2007	8	10.1016/j.jaci.2006.12.609	Allergy; Immunology
Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension. In the present study, the hypothesis that dendritic cells (DCs), key players in immunity and tolerance, might be involved in the immunopathology of idiopathic pulmonary arterial hypertension (IPAH) was tested. The phenotype and localisation of DCs were characterised by immunohistochemistry and double-labelling immunofluorescence in lung samples from controls, human IPAH patients and an experimental pulmonary hypertension model (monocrotaline-exposed rats). As compared with controls, morphometric analysis demonstrated increased numbers of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN)-positive cells in muscular pulmonary arteries in IPAH and OX-62-positive DCs in monocrotaline-induced pulmonary hypertension. In human samples, the mean +/- SEM number of DC-SIGN-positive cells(.)artery(-1) of 100-300 mu m diameter was 1.4 +/- 0.4 in controls versus 26.4 +/- 2.7 in IPAH. In rats, the number of OX-62-positive cells(.)artery(-1) of 50-150 mu m diameter was 0.5 +/- 0.2 in controls, and 0.7 +/- 0.5, 3.1 +/- 0.5 and 8.4 +/- 0.6 at day 7, 14 and 28 after monocrotaline exposure, respectively. Human complex lesions of muscular pulmonary arteries showed transmural DC infiltration. Phenotyping revealed an immature DC profile in human and experimental pulmonary hypertension. The results support the concept that immature dendritic cells accumulate in remodelled pulmonary vessels and hence could be involved in the immunopathology of pulmonary hypertension.. dendritic cells| immunopathology| inflammation| monocrotaline| pulmonary arterial hypertension|arterial-hypertension| imatinib mesylate| peripheral-blood| tumor| precursors| antibodies| diseases| asthma.	MAR-2007	dendritic cells| immunopathology| inflammation| monocrotaline| pulmonary arterial hypertension|arterial-hypertension| imatinib mesylate| peripheral-blood| tumor| precursors| antibodies| diseases| asthma	Perros, F; Dorfmuller, P; Souza, R; Durand-Gasselin, I; Mussot, S; Mazmanian, M; Herve, P; Emilie, D; Simonneau, G; Humbert, M	Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension		EUROPEAN RESPIRATORY JOURNAL	dendritic cells; immunopathology; inflammation; monocrotaline; pulmonary arterial hypertension	ARTERIAL-HYPERTENSION; IMATINIB MESYLATE; PERIPHERAL-BLOOD; TUMOR; PRECURSORS; ANTIBODIES; DISEASES; ASTHMA	In the present study, the hypothesis that dendritic cells (DCs), key players in immunity and tolerance, might be involved in the immunopathology of idiopathic pulmonary arterial hypertension (IPAH) was tested. The phenotype and localisation of DCs were characterised by immunohistochemistry and double-labelling immunofluorescence in lung samples from controls, human IPAH patients and an experimental pulmonary hypertension model (monocrotaline-exposed rats). As compared with controls, morphometric analysis demonstrated increased numbers of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN)-positive cells in muscular pulmonary arteries in IPAH and OX-62-positive DCs in monocrotaline-induced pulmonary hypertension. In human samples, the mean +/- SEM number of DC-SIGN-positive cells(.)artery(-1) of 100-300 mu m diameter was 1.4 +/- 0.4 in controls versus 26.4 +/- 2.7 in IPAH. In rats, the number of OX-62-positive cells(.)artery(-1) of 50-150 mu m diameter was 0.5 +/- 0.2 in controls, and 0.7 +/- 0.5, 3.1 +/- 0.5 and 8.4 +/- 0.6 at day 7, 14 and 28 after monocrotaline exposure, respectively. Human complex lesions of muscular pulmonary arteries showed transmural DC infiltration. Phenotyping revealed an immature DC profile in human and experimental pulmonary hypertension. The results support the concept that immature dendritic cells accumulate in remodelled pulmonary vessels and hence could be involved in the immunopathology of pulmonary hypertension.	41	73	2007	7	10.1183/09031936.00094706	Respiratory System
The pharmacology of particulate matter air pollution-induced cardiovascular dysfunction. Since the London fog of 1952, in which more than 4000 people were killed in 4 days, the combined efforts of scientists from several disciplines, including those from the environmental health, clinical and biomedical disciplines, have raised serious concerns about the impact of air pollutants on human health. These environmental pollutants are rapidly being recognized as important and independent risk factors for several diseases such as asthma, chronic obstructive pulmonary disease, lung cancer, atherosclerosis, ischemic heart disease and stroke. Although the relative effects of particulate matter air pollution (aerodynamic diameter < 10 mu m, or PM10) are greater for respiratory than for cardiovascular deaths, the number of deaths attributable to PM10 is much larger for cardiovascular than for respiratory reasons due to the higher prevalence of cardiovascular disease in the general population. This review summarizes current understanding of the mechanisms underlying the associations between PM10 exposure and cardiovascular morbidity and mortality. (c) 2006 Elsevier Inc. All rights reserved.. particulate matter air pollution| inflammation| cardiovascular effect| reactive oxygen species| endothelial dysfunction|c-reactive protein| diesel exhaust particles| heart-rate-variability| coronary-artery-disease| ultrafine carbon-black| bronchial epithelial-cells| human alveolar macrophages| human endothelial-cells| smooth-muscle-cells| south-polar-plateau.	JAN-2007	particulate matter air pollution| inflammation| cardiovascular effect| reactive oxygen species| endothelial dysfunction|c-reactive protein| diesel exhaust particles| heart-rate-variability| coronary-artery-disease| ultrafine carbon-black| bronchial epithelial-cells| human alveolar macrophages| human endothelial-cells| smooth-muscle-cells| south-polar-plateau	Bai, N; Khazaei, M; van Eeden, SF; Laher, I	The pharmacology of particulate matter air pollution-induced cardiovascular dysfunction		PHARMACOLOGY & THERAPEUTICS	particulate matter air pollution; inflammation; cardiovascular effect; reactive oxygen species; endothelial dysfunction	C-REACTIVE PROTEIN; DIESEL EXHAUST PARTICLES; HEART-RATE-VARIABILITY; CORONARY-ARTERY-DISEASE; ULTRAFINE CARBON-BLACK; BRONCHIAL EPITHELIAL-CELLS; HUMAN ALVEOLAR MACROPHAGES; HUMAN ENDOTHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; SOUTH-POLAR-PLATEAU	Since the London fog of 1952, in which more than 4000 people were killed in 4 days, the combined efforts of scientists from several disciplines, including those from the environmental health, clinical and biomedical disciplines, have raised serious concerns about the impact of air pollutants on human health. These environmental pollutants are rapidly being recognized as important and independent risk factors for several diseases such as asthma, chronic obstructive pulmonary disease, lung cancer, atherosclerosis, ischemic heart disease and stroke. Although the relative effects of particulate matter air pollution (aerodynamic diameter < 10 mu m, or PM10) are greater for respiratory than for cardiovascular deaths, the number of deaths attributable to PM10 is much larger for cardiovascular than for respiratory reasons due to the higher prevalence of cardiovascular disease in the general population. This review summarizes current understanding of the mechanisms underlying the associations between PM10 exposure and cardiovascular morbidity and mortality. (c) 2006 Elsevier Inc. All rights reserved.	193	73	2007	14	10.1016/j.pharmthera.2006.06.005	Pharmacology & Pharmacy
Inhibition of spleen tyrosine kinase prevents mast cell activation and airway hyperresponsiveness. Rationale: Spleen tyrosine kinase (Syk) is important for Fc and B-cell receptor-mediated signaling. Objective: To determine the activity of a specific Syk inhibitor (11406) on mast cell activation in vitro and on the development of allergen-induced airway hyperresponsiveness (AHR) and inflammation in vivo. Methods: AHR and inflammation were induced after 10 d of allergen (ovalbumin [OVA]) exposure exclusively via the airways and in the absence of adjuvant. This approach was previously established to be IgE, Fc epsilon RI, and mast cell dependent. Alternatively, mice were passively sensitized with OVA-specific IgE, followed by limited airway challenge. In vitro, the inhibitor was added to cultures of IgE-sensitized bone marrow-derived mast cells (BMMCs) before crosslinking with allergen. Results: The inhibitor prevented OVA-induced degranulation of passively IgE-sensitized murine IBMMCs and inhibited the production of interieukin (IL)-13, tumor necrosis factor a, IL-2, and IL-6 in these sensitized BMMCs. When administered in vivo, R406 inhibited AHR, which developed in BALB/c mice exposed to aerosolized 1% OVA for 10 consecutive d (20 min/d), as well as pulmonary eosinophilia and goblet cell metaplasia. A similar inhibition of AHR was demonstrated in mice passively sensitized with OVA-specific IgE and exposed to limited airway challenge. Conclusion: This study delineates a functional role for Syk in the development of mast cell- and IgE-mediated AHR and airway inflammation, and these results indicate that inhibition of Syk may be a target in the treatment of allergic asthma.. airway hyperresponsiveness| eosinophils| goblet cell metaplasia| mast cells| spleen tyrosine kinase|affinity ige receptor| fc-epsilon-ri| cd8(+) t-cells| passive transfer| terminal kinase| allergic-asthma| smooth-muscle| inflammation| syk| protein.	JAN 1-2006	airway hyperresponsiveness| eosinophils| goblet cell metaplasia| mast cells| spleen tyrosine kinase|affinity ige receptor| fc-epsilon-ri| cd8(+) t-cells| passive transfer| terminal kinase| allergic-asthma| smooth-muscle| inflammation| syk| protein	Matsubara, S; Li, GM; Takeda, K; Loader, JE; Pine, P; Masuda, ES; Miyahara, N; Miyahara, S; Lucas, JJ; Dakhama, A; Gelfand, EW	Inhibition of spleen tyrosine kinase prevents mast cell activation and airway hyperresponsiveness		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	airway hyperresponsiveness; eosinophils; goblet cell metaplasia; mast cells; spleen tyrosine kinase	AFFINITY IGE RECEPTOR; FC-EPSILON-RI; CD8(+) T-CELLS; PASSIVE TRANSFER; TERMINAL KINASE; ALLERGIC-ASTHMA; SMOOTH-MUSCLE; INFLAMMATION; SYK; PROTEIN	Rationale: Spleen tyrosine kinase (Syk) is important for Fc and B-cell receptor-mediated signaling. Objective: To determine the activity of a specific Syk inhibitor (11406) on mast cell activation in vitro and on the development of allergen-induced airway hyperresponsiveness (AHR) and inflammation in vivo. Methods: AHR and inflammation were induced after 10 d of allergen (ovalbumin [OVA]) exposure exclusively via the airways and in the absence of adjuvant. This approach was previously established to be IgE, Fc epsilon RI, and mast cell dependent. Alternatively, mice were passively sensitized with OVA-specific IgE, followed by limited airway challenge. In vitro, the inhibitor was added to cultures of IgE-sensitized bone marrow-derived mast cells (BMMCs) before crosslinking with allergen. Results: The inhibitor prevented OVA-induced degranulation of passively IgE-sensitized murine IBMMCs and inhibited the production of interieukin (IL)-13, tumor necrosis factor a, IL-2, and IL-6 in these sensitized BMMCs. When administered in vivo, R406 inhibited AHR, which developed in BALB/c mice exposed to aerosolized 1% OVA for 10 consecutive d (20 min/d), as well as pulmonary eosinophilia and goblet cell metaplasia. A similar inhibition of AHR was demonstrated in mice passively sensitized with OVA-specific IgE and exposed to limited airway challenge. Conclusion: This study delineates a functional role for Syk in the development of mast cell- and IgE-mediated AHR and airway inflammation, and these results indicate that inhibition of Syk may be a target in the treatment of allergic asthma.	45	73	2006	8	10.1164/rccm.200503-361OC	General & Internal Medicine; Respiratory System
Cost-effectiveness of a home-based environmental intervention for inner-city children with asthma. Background: Exposure to indoor allergens contributes to increased asthma morbidity. The Inner-City Asthma Study, a randomized trial involving home environmental allergen and irritant remediation among children aged 6 through 11 years with moderate-to-severe asthma, successfully reduced asthma symptoms. A cost-effectiveness analysis can help stakeholders to evaluate the potential costs and benefits of adopting such a program. Objective: We sought to assess the cost-effectiveness of the environmental intervention of the Inner-City Asthma Study. Methods: Incremental cost-effectiveness ratios for a 2-year study period were calculated. Health outcome was measured as symptom-free days. Resource use measures included ambulatory visits, hospitalizations, and pharmaceutical use. CIs were obtained by using bootstrapping. Results: The intervention, which cost $1469 per family, led to statistically significant reductions in symptom days, unscheduled clinic visits, and use of beta-agonist inhalers. Over the year of the intervention and a year of follow-up, the intervention cost was $27.57 per additional symptom-free day (95% CI, $7.46-$67.42). Subgroup analysis showed that targeting the intervention to selected high-risk subgroups did not reduce the incremental cost-effectiveness ratio. Conclusions: A targeted home-based environmental intervention improved health and reduced service use in inner-city children with moderate-to-severe asthma. The intervention is cost-effective when the aim is to reduce asthma symptom days and the associated costs.. asthma| inner city| cost-effectiveness| asthma intervention| allergen mitigation|united-states| illness| trends.	NOV-2005	asthma| inner city| cost-effectiveness| asthma intervention| allergen mitigation|united-states| illness| trends	Kattan, M; Stearns, SC; Crain, EF; Stout, JW; Gergen, PJ; Evans, R; Visness, CM; Gruchalla, RS; Morgan, WJ; O'Connor, GT; Mastin, JP; Mitchell, HE	Cost-effectiveness of a home-based environmental intervention for inner-city children with asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; inner city; cost-effectiveness; asthma intervention; allergen mitigation	UNITED-STATES; ILLNESS; TRENDS	Background: Exposure to indoor allergens contributes to increased asthma morbidity. The Inner-City Asthma Study, a randomized trial involving home environmental allergen and irritant remediation among children aged 6 through 11 years with moderate-to-severe asthma, successfully reduced asthma symptoms. A cost-effectiveness analysis can help stakeholders to evaluate the potential costs and benefits of adopting such a program. Objective: We sought to assess the cost-effectiveness of the environmental intervention of the Inner-City Asthma Study. Methods: Incremental cost-effectiveness ratios for a 2-year study period were calculated. Health outcome was measured as symptom-free days. Resource use measures included ambulatory visits, hospitalizations, and pharmaceutical use. CIs were obtained by using bootstrapping. Results: The intervention, which cost $1469 per family, led to statistically significant reductions in symptom days, unscheduled clinic visits, and use of beta-agonist inhalers. Over the year of the intervention and a year of follow-up, the intervention cost was $27.57 per additional symptom-free day (95% CI, $7.46-$67.42). Subgroup analysis showed that targeting the intervention to selected high-risk subgroups did not reduce the incremental cost-effectiveness ratio. Conclusions: A targeted home-based environmental intervention improved health and reduced service use in inner-city children with moderate-to-severe asthma. The intervention is cost-effective when the aim is to reduce asthma symptom days and the associated costs.	14	73	2005	6	10.1016/j.jaci.2005.07.032	Allergy; Immunology
Constitutive expression of aryl hydrocarbon receptor in keratinocytes causes inflammatory skin lesions. Occupational and environmental exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to provoke inflammatory and/or allergic disorders, including asthma, rhinitis, and dermatitis. The molecular mechanisms of this PAH-mediated inflammation remain to be clarified. Previous studies implied the involvement of PAHs as irritants and allergens, with the reactive oxygen species generated from the oxygenated PAHs believed to be an exacerbating factor. It is also possible that PAHs contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription, since PAHs are potent inducers of the AhR. To address this point, we generated transgenic mouse lines expressing the constitutive active form of the AhR in keratinocytes. In these lines of mice, the AhR activity was constitutively enhanced in the absence of ligands, so that any other direct effects of PAHs and their metabolites could be ignored. At birth, these transgenic mice were normal, but severe skin lesions with itching developed postnatally. The skin lesions were accompanied by inflammation and immunological imbalance and resembled typical atopic dermatitis. We demonstrate that constitutive activation of the AhR pathway causes inflammatory skin lesions and suggests a new mechanism for the exacerbation of inflammatory diseases after exposure to occupational and environmental xenobiotics.. polycyclic aromatic-hydrocarbons| diesel exhaust particles| contact hypersensitivity| 2,3,7,8-tetrachlorodibenzo-p-dioxin tcdd| polyaromatic hydrocarbons| atopic-dermatitis| dioxin receptor| transgenic mice| ige| induction.	NOV-2005	polycyclic aromatic-hydrocarbons| diesel exhaust particles| contact hypersensitivity| 2,3,7,8-tetrachlorodibenzo-p-dioxin tcdd| polyaromatic hydrocarbons| atopic-dermatitis| dioxin receptor| transgenic mice| ige| induction	Tauchi, M; Hida, A; Negishi, T; Katsuoka, F; Noda, S; Mimura, J; Hosoya, T; Yanaka, A; Aburatani, H; Fujii-Kuriyama, Y; Motohashi, H; Yamamoto, M	Constitutive expression of aryl hydrocarbon receptor in keratinocytes causes inflammatory skin lesions		MOLECULAR AND CELLULAR BIOLOGY		POLYCYCLIC AROMATIC-HYDROCARBONS; DIESEL EXHAUST PARTICLES; CONTACT HYPERSENSITIVITY; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; POLYAROMATIC HYDROCARBONS; ATOPIC-DERMATITIS; DIOXIN RECEPTOR; TRANSGENIC MICE; IGE; INDUCTION	Occupational and environmental exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to provoke inflammatory and/or allergic disorders, including asthma, rhinitis, and dermatitis. The molecular mechanisms of this PAH-mediated inflammation remain to be clarified. Previous studies implied the involvement of PAHs as irritants and allergens, with the reactive oxygen species generated from the oxygenated PAHs believed to be an exacerbating factor. It is also possible that PAHs contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription, since PAHs are potent inducers of the AhR. To address this point, we generated transgenic mouse lines expressing the constitutive active form of the AhR in keratinocytes. In these lines of mice, the AhR activity was constitutively enhanced in the absence of ligands, so that any other direct effects of PAHs and their metabolites could be ignored. At birth, these transgenic mice were normal, but severe skin lesions with itching developed postnatally. The skin lesions were accompanied by inflammation and immunological imbalance and resembled typical atopic dermatitis. We demonstrate that constitutive activation of the AhR pathway causes inflammatory skin lesions and suggests a new mechanism for the exacerbation of inflammatory diseases after exposure to occupational and environmental xenobiotics.	38	73	2005	9	10.1128/MCB.25.21.9360-9368.2005	Biochemistry & Molecular Biology; Cell Biology
Change in prevalence of IgE sensitization and mean total IgE with age and cohort. Background: Cross-sectional studies show that the prevalence of IgE sensitization is lower in older age groups than younger age groups. This could reflect either a decrease in sensitization with aging or a higher prevalence of sensitization in more recent birth cohorts. Objective: To assess change in IgE sensitization and mean total IgE in young adults as they age. Methods: Serum specific IgE to common allergens and total IgE were measured on 2 occasions about 9 years apart in 6371 young adults living in 28 centers, mainly in Western Europe, who took part in the European Community Respiratory Health Survey II. Outcomes were analyzed by using generalized estimating equations, and adjustments were made for differences between laboratory measures on the 2 occasions. Results: Overall, there was no net change in the prevalence of sensitization to at least 1 of house dust mite, grass, or cat (net change per 10 years of follow-up, -0.1%; 95% CI, -1.7% to 1.5%), although there was a fall in mean total IgE (ratio of geometric mean total IgE, 0.86; 95% CI, 0.79 to 0.93). There was evidence that sensitization to at least 1 allergen was higher in more recent cohorts, and this was largely explained by a higher prevalence of sensitization to grass. Conclusion: The disease burden associated with IgE sensitization in adults, and particularly with IgE sensitization to grass, is likely to continue to increase for some time despite current evidence that the increase in allergy seen in children may have ceased.. ecrhs| atopy| total ige| cohort|respiratory-health-survey| skin-test reactivity| 8 years apart| hay-fever| serum ige| immunoglobulin-e| increasing prevalence| copenhagen allergy| asthma| atopy.	SEP-2005	ecrhs| atopy| total ige| cohort|respiratory-health-survey| skin-test reactivity| 8 years apart| hay-fever| serum ige| immunoglobulin-e| increasing prevalence| copenhagen allergy| asthma| atopy	Jarvis, D; Luczynska, C; Chinn, S; Potts, J; Sunyer, J; Janson, C; Svanes, C; Kunzli, N; Leynaert, B; Heinrich, J; Kerkhof, M; Ackermann-Liebrich, U; Anto, MM; Cerveri, I; de Marco, R; Gislason, T; Neukirch, F; Vermeire, P; Wjst, M; Burney, P	Change in prevalence of IgE sensitization and mean total IgE with age and cohort		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	ECRHS; atopy; total IgE; cohort	RESPIRATORY-HEALTH-SURVEY; SKIN-TEST REACTIVITY; 8 YEARS APART; HAY-FEVER; SERUM IGE; IMMUNOGLOBULIN-E; INCREASING PREVALENCE; COPENHAGEN ALLERGY; ASTHMA; ATOPY	Background: Cross-sectional studies show that the prevalence of IgE sensitization is lower in older age groups than younger age groups. This could reflect either a decrease in sensitization with aging or a higher prevalence of sensitization in more recent birth cohorts. Objective: To assess change in IgE sensitization and mean total IgE in young adults as they age. Methods: Serum specific IgE to common allergens and total IgE were measured on 2 occasions about 9 years apart in 6371 young adults living in 28 centers, mainly in Western Europe, who took part in the European Community Respiratory Health Survey II. Outcomes were analyzed by using generalized estimating equations, and adjustments were made for differences between laboratory measures on the 2 occasions. Results: Overall, there was no net change in the prevalence of sensitization to at least 1 of house dust mite, grass, or cat (net change per 10 years of follow-up, -0.1%; 95% CI, -1.7% to 1.5%), although there was a fall in mean total IgE (ratio of geometric mean total IgE, 0.86; 95% CI, 0.79 to 0.93). There was evidence that sensitization to at least 1 allergen was higher in more recent cohorts, and this was largely explained by a higher prevalence of sensitization to grass. Conclusion: The disease burden associated with IgE sensitization in adults, and particularly with IgE sensitization to grass, is likely to continue to increase for some time despite current evidence that the increase in allergy seen in children may have ceased.	31	73	2005	8	10.1016/j.jaci.2005.05.009	Allergy; Immunology
Antibiotic exposure in early infancy and risk for childhood atopy. Background: The increase in pediatric allergy and asthma parallels the increase in use of antibiotics. Antibiotics disturb the flora of the gastrointestinal tract, possibly perturbing the developing immune system. Objective: We evaluated whether antibiotic use during early infancy increased the risk for atopy. Methods: Antibiotic prescriptions documented in medical records were collected from a birth cohort born from 1987 through 1989 (n=725). At 6 to 7 years of age, 448 were followed by means of examination, including skin prick tests and serum IgE measurements to common allergens. Results: Adjusted odds ratios (aORs) and 95% CIs were calculated comparing children with any versus those with no antibiotic use in the first 6 months and the outcomes of atopy (any positive skin test response), seroatopy (any positive specific IgE test result), either atopy or seroatopy, and both atopy and seroatopy. Atopy increased with antibiotic use approaching statistical significance (aOR, 1.48, 95% Cl, 0.94-2.34; P =.09)., however, the risk was concentrated among children with less than 2 pets in the home (aOR, 1.73; 95% Cl, 1.07-2.80; P=.024) and children breast-fed for 4 or more months (aOR, 3.02; 95% CI, 1.27-7.17; P=.013). The aORs were generally in the same direction for seroatopy and the combined categories. Conclusion: Antibiotic use in early life appears to contribute to increased risk for atopy in certain subgroups of children.. allergy| antibiotics| atopy| children| ige| skin testing|practice research database| allergic disease| infectious-diseases| birth cohort| serum ige| 1st year| asthma| life| age| children.	JUN-2005	allergy| antibiotics| atopy| children| ige| skin testing|practice research database| allergic disease| infectious-diseases| birth cohort| serum ige| 1st year| asthma| life| age| children	Johnson, CC; Ownby, DR; Alford, SH; Havstad, SL; Williams, LK; Zoratti, EM; Peterson, EL; Joseph, CLM	Antibiotic exposure in early infancy and risk for childhood atopy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; antibiotics; atopy; children; IgE; skin testing	PRACTICE RESEARCH DATABASE; ALLERGIC DISEASE; INFECTIOUS-DISEASES; BIRTH COHORT; SERUM IGE; 1ST YEAR; ASTHMA; LIFE; AGE; CHILDREN	Background: The increase in pediatric allergy and asthma parallels the increase in use of antibiotics. Antibiotics disturb the flora of the gastrointestinal tract, possibly perturbing the developing immune system. Objective: We evaluated whether antibiotic use during early infancy increased the risk for atopy. Methods: Antibiotic prescriptions documented in medical records were collected from a birth cohort born from 1987 through 1989 (n=725). At 6 to 7 years of age, 448 were followed by means of examination, including skin prick tests and serum IgE measurements to common allergens. Results: Adjusted odds ratios (aORs) and 95% CIs were calculated comparing children with any versus those with no antibiotic use in the first 6 months and the outcomes of atopy (any positive skin test response), seroatopy (any positive specific IgE test result), either atopy or seroatopy, and both atopy and seroatopy. Atopy increased with antibiotic use approaching statistical significance (aOR, 1.48, 95% Cl, 0.94-2.34; P =.09)., however, the risk was concentrated among children with less than 2 pets in the home (aOR, 1.73; 95% Cl, 1.07-2.80; P=.024) and children breast-fed for 4 or more months (aOR, 3.02; 95% CI, 1.27-7.17; P=.013). The aORs were generally in the same direction for seroatopy and the combined categories. Conclusion: Antibiotic use in early life appears to contribute to increased risk for atopy in certain subgroups of children.	27	73	2005	7	10.1016/j.jaci.2005.04.020	Allergy; Immunology
Occupational hypersensitivity to metal salts, including platinum, in the secondary industry. Background: Exposure to platinum group elements (PGEs) - platinum (Pt), palladium (Pd), rhodium (Rh) and iridium (Ir) - may cause acute toxicity or hypersensitivity with respiratory symptoms, urticaria and (less frequently) contact dermatitis. Our aim was to determine the prevalence and the clinical characteristics of hypersensitivity to platinum salts and to other elements of the platinum group. Methods: A total of 153 subjects working in a catalyst manufacturing and recycling factory were examined. The examination consisted of a work exposure and medical questionnaire, physical examination, skin prick test for PGEs and other common aeroallergens, and patch tests for PGEs. Skin prick tests and patch tests were performed with H-2[PtCl6], K-2[PtCl4], Na-2[PtCl6], IrCl3, RhCl3, PdCl2, aqueous solutions at different concentrations. Results: Positive prick test reactions to Pt-salts at various concentrations were found in 22 (14.4%) of 153 workers; eight had simultaneous reactions to all Pt-salts tested; seven had positive responses to H-2[PtCl6] only; four had simultaneous positive reactions to both H-2[PtCl6] and K-2[PtCl4]; three had positive reactions to H-2[PtCl6] and Na-2[PtCl6]. Three of 22 had positive reactions to H-2[PtCl6] and IrCl3 solutions, two of these had positive reactions to H-2[PtCl6], IrCl3 and RhCl3 solutions. Positive patch test reactions to platinum salts at day 2 were seen in two of 153 subjects. Conclusions: The results of this study demonstrate that Pt-salts are important allergens in the catalyst industry and that the clinical manifestations involve both the respiratory system and the skin. Hexachloroplatinic acid should be considered the most important salt to use for skin prick tests.. hypersensitivity| iridium| occupational| palladium| platinum group elements| platinum salts| rhodium| skin test|refinery workers| medical surveillance| prospective cohort| allergy| exposure| asthma.	FEB-2005	hypersensitivity| iridium| occupational| palladium| platinum group elements| platinum salts| rhodium| skin test|refinery workers| medical surveillance| prospective cohort| allergy| exposure| asthma	Cristaudo, A; Sera, F; Severino, V; De Rocco, M; Di Lella, E; Picardo, M	Occupational hypersensitivity to metal salts, including platinum, in the secondary industry		ALLERGY	hypersensitivity; iridium; occupational; palladium; platinum group elements; platinum salts; rhodium; skin test	REFINERY WORKERS; MEDICAL SURVEILLANCE; PROSPECTIVE COHORT; ALLERGY; EXPOSURE; ASTHMA	Background: Exposure to platinum group elements (PGEs) - platinum (Pt), palladium (Pd), rhodium (Rh) and iridium (Ir) - may cause acute toxicity or hypersensitivity with respiratory symptoms, urticaria and (less frequently) contact dermatitis. Our aim was to determine the prevalence and the clinical characteristics of hypersensitivity to platinum salts and to other elements of the platinum group. Methods: A total of 153 subjects working in a catalyst manufacturing and recycling factory were examined. The examination consisted of a work exposure and medical questionnaire, physical examination, skin prick test for PGEs and other common aeroallergens, and patch tests for PGEs. Skin prick tests and patch tests were performed with H-2[PtCl6], K-2[PtCl4], Na-2[PtCl6], IrCl3, RhCl3, PdCl2, aqueous solutions at different concentrations. Results: Positive prick test reactions to Pt-salts at various concentrations were found in 22 (14.4%) of 153 workers; eight had simultaneous reactions to all Pt-salts tested; seven had positive responses to H-2[PtCl6] only; four had simultaneous positive reactions to both H-2[PtCl6] and K-2[PtCl4]; three had positive reactions to H-2[PtCl6] and Na-2[PtCl6]. Three of 22 had positive reactions to H-2[PtCl6] and IrCl3 solutions, two of these had positive reactions to H-2[PtCl6], IrCl3 and RhCl3 solutions. Positive patch test reactions to platinum salts at day 2 were seen in two of 153 subjects. Conclusions: The results of this study demonstrate that Pt-salts are important allergens in the catalyst industry and that the clinical manifestations involve both the respiratory system and the skin. Hexachloroplatinic acid should be considered the most important salt to use for skin prick tests.	20	73	2005	6	10.1111/j.1398-9995.2004.00521.x	Allergy; Immunology
The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass. Particle exposure has traditionally been monitored as mass concentration of PM10 (particles with an aerodynamic diameter less than 10 mum), more recently also as PM2.5. The mass concentration is strongly influenced by the large particles. Therefore, particle mass is a poor measure for characterizing the amount of the small, possibly more biologically potent particles. We used polystyrene particles (PSP) ranging in diameter from 0.0588 to 11.14 mum, carbon black (CB), and diesel exhaust particles (DEP), to study the adjuvant effect of particles on the immune response to the allergen ovalbumin (OVA) after sc injection into the footpad of BALB/cA mice. At a given mass dose, the small particles (0.0588 and 0.202 mum PSP, CB, and DEP) increased the allergen-specific IgE serum levels to a substantially higher degree than the larger particles (1.053, 4.64, and 11.14 mum PSP). Further, in the draining lymph node during the primary response, the fine particles (0.202 mum) with OVA increased cell numbers, expression of surface markers (CD19, MHC class II, CD86, and CD23) and ex vivo production of IL-4 and IL-10, whereas the largest (11.14 mum) particles did not. Linear regression analyses indicated that the IgE response was not predicted by particle mass (R-2 = 0.06), but was predicted by the total particle surface area (R-2 = 0.64), number of particles (R-2 = 0.62), and particle diameter (R-2 = 0.58). In conclusion, we found that fine particles exerted stronger adjuvant effects on allergic responses than larger particles at equal mass doses. Consequently, the dose described as total particle surface area or particle number predicts the adjuvant effect of particles better than the currently used particle mass.. pm| particle size| adjuvant effect| allergy| mice| ige|diesel exhaust particles| carbon-black| particulate matter| air-pollution| ultrafine particles| urban air| respiratory health| adjuvant activity| oxidative stress| immune-responses.	DEC-2004	pm| particle size| adjuvant effect| allergy| mice| ige|diesel exhaust particles| carbon-black| particulate matter| air-pollution| ultrafine particles| urban air| respiratory health| adjuvant activity| oxidative stress| immune-responses	Nygaard, UC; Samuelsen, M; Aase, A; Lovik, M	The capacity of particles to increase allergic sensitization is predicted by particle number and surface area, not by particle mass		TOXICOLOGICAL SCIENCES	PM; particle size; adjuvant effect; allergy; mice; IgE	DIESEL EXHAUST PARTICLES; CARBON-BLACK; PARTICULATE MATTER; AIR-POLLUTION; ULTRAFINE PARTICLES; URBAN AIR; RESPIRATORY HEALTH; ADJUVANT ACTIVITY; OXIDATIVE STRESS; IMMUNE-RESPONSES	Particle exposure has traditionally been monitored as mass concentration of PM10 (particles with an aerodynamic diameter less than 10 mum), more recently also as PM2.5. The mass concentration is strongly influenced by the large particles. Therefore, particle mass is a poor measure for characterizing the amount of the small, possibly more biologically potent particles. We used polystyrene particles (PSP) ranging in diameter from 0.0588 to 11.14 mum, carbon black (CB), and diesel exhaust particles (DEP), to study the adjuvant effect of particles on the immune response to the allergen ovalbumin (OVA) after sc injection into the footpad of BALB/cA mice. At a given mass dose, the small particles (0.0588 and 0.202 mum PSP, CB, and DEP) increased the allergen-specific IgE serum levels to a substantially higher degree than the larger particles (1.053, 4.64, and 11.14 mum PSP). Further, in the draining lymph node during the primary response, the fine particles (0.202 mum) with OVA increased cell numbers, expression of surface markers (CD19, MHC class II, CD86, and CD23) and ex vivo production of IL-4 and IL-10, whereas the largest (11.14 mum) particles did not. Linear regression analyses indicated that the IgE response was not predicted by particle mass (R-2 = 0.06), but was predicted by the total particle surface area (R-2 = 0.64), number of particles (R-2 = 0.62), and particle diameter (R-2 = 0.58). In conclusion, we found that fine particles exerted stronger adjuvant effects on allergic responses than larger particles at equal mass doses. Consequently, the dose described as total particle surface area or particle number predicts the adjuvant effect of particles better than the currently used particle mass.	44	73	2004	10	10.1093/toxsci/kfh287	Toxicology
Glutathione S-transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma. Background Polymorphisms at the glutathione S-transferase (GST) P1 locus were associated with asthma-related phenotypes and bronchial hyper-responsiveness. Objective This study investigated whether GSTP1 genotypes and outdoor air pollution were interactive risk factors on childhood asthma. Methods Four hundred and thirty-six subjects were recruited for oral mucosa samplings from 2853 fourth- to ninth-grade schoolchildren from three districts with different air pollution levels in southern Taiwan. PCR-based assays were performed by oral mucosa DNA to determine GSTP1 genotypes. We also conducted a nested case-control study comprising 61 asthmatic children and 95 controls confirmed by International Study of Asthma and Allergies in Childhood questionnaire results and methacholine challenge test. Multiple logistic regression was used to adjust for potential confounding factors. Results All participants were homozygous at the Ala-114 locus. Although only a marginally significant association existed between the frequency of homozygosity at the Ile-105 locus and asthma when air pollution was not considered, we found a significant gene-environmental interaction between GSTP1-105 alleles and air pollution after adjusting for confounders (P=0.035). Specifically, we found that compared with participants carrying any Val-105 allele in low air pollution, those who are Ile-105 homozygotes in high air pollution district had a significantly increased risk of asthma (adjusted odds ratio (AOR)=5.52, 95% confidence interval (CI)=1.64-21.25). Compared with participants carrying any Val-105 allele, in high air pollution district, children with Ile-105 homozygotes had a significantly increased risk of asthma (AOR=3.79, 95% CI=1.01-17.08), but those who carried two Ile-105 alleles in low or moderate air pollution districts did not show similar tendencies. The risk of asthma also revealed a clear dose-response relationship with outdoor air pollution in children with Ile-105 homozygotes. Conclusion Our result suggests a gene-environmental interaction between GSTP1-105 genotypes and outdoor air pollution on childhood asthma.. air pollution| asthma| children| gene-environmental interaction| gstp1 polymorphism|genome-wide search| bronchial hyperresponsiveness| respiratory symptoms| environmental exposures| susceptibility loci| pulmonary-function| immunoglobulin-e| school-children| gstp1 locus| atopy.	NOV-2004	air pollution| asthma| children| gene-environmental interaction| gstp1 polymorphism|genome-wide search| bronchial hyperresponsiveness| respiratory symptoms| environmental exposures| susceptibility loci| pulmonary-function| immunoglobulin-e| school-children| gstp1 locus| atopy	Lee, YL; Lin, YC; Lee, YC; Wang, JY; Hsiue, TR; Guo, YL	Glutathione S-transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma		CLINICAL AND EXPERIMENTAL ALLERGY	air pollution; asthma; children; gene-environmental interaction; GSTP1 polymorphism	GENOME-WIDE SEARCH; BRONCHIAL HYPERRESPONSIVENESS; RESPIRATORY SYMPTOMS; ENVIRONMENTAL EXPOSURES; SUSCEPTIBILITY LOCI; PULMONARY-FUNCTION; IMMUNOGLOBULIN-E; SCHOOL-CHILDREN; GSTP1 LOCUS; ATOPY	Background Polymorphisms at the glutathione S-transferase (GST) P1 locus were associated with asthma-related phenotypes and bronchial hyper-responsiveness. Objective This study investigated whether GSTP1 genotypes and outdoor air pollution were interactive risk factors on childhood asthma. Methods Four hundred and thirty-six subjects were recruited for oral mucosa samplings from 2853 fourth- to ninth-grade schoolchildren from three districts with different air pollution levels in southern Taiwan. PCR-based assays were performed by oral mucosa DNA to determine GSTP1 genotypes. We also conducted a nested case-control study comprising 61 asthmatic children and 95 controls confirmed by International Study of Asthma and Allergies in Childhood questionnaire results and methacholine challenge test. Multiple logistic regression was used to adjust for potential confounding factors. Results All participants were homozygous at the Ala-114 locus. Although only a marginally significant association existed between the frequency of homozygosity at the Ile-105 locus and asthma when air pollution was not considered, we found a significant gene-environmental interaction between GSTP1-105 alleles and air pollution after adjusting for confounders (P=0.035). Specifically, we found that compared with participants carrying any Val-105 allele in low air pollution, those who are Ile-105 homozygotes in high air pollution district had a significantly increased risk of asthma (adjusted odds ratio (AOR)=5.52, 95% confidence interval (CI)=1.64-21.25). Compared with participants carrying any Val-105 allele, in high air pollution district, children with Ile-105 homozygotes had a significantly increased risk of asthma (AOR=3.79, 95% CI=1.01-17.08), but those who carried two Ile-105 alleles in low or moderate air pollution districts did not show similar tendencies. The risk of asthma also revealed a clear dose-response relationship with outdoor air pollution in children with Ile-105 homozygotes. Conclusion Our result suggests a gene-environmental interaction between GSTP1-105 genotypes and outdoor air pollution on childhood asthma.	40	73	2004	7	10.1111/j.1365-2222.2004.02099.x	Allergy; Immunology
A novel model of sensitization and oral tolerance to peanut protein. The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens.. sensitization| oral tolerance| peanut| allergy|immune-responses| t-cells| atopic-dermatitis| suppression| allergen| prevalence| antigens| identification| induction| ovalbumin.	NOV-2004	sensitization| oral tolerance| peanut| allergy|immune-responses| t-cells| atopic-dermatitis| suppression| allergen| prevalence| antigens| identification| induction| ovalbumin	Strid, J; Thomson, M; Hourihane, J; Kimber, I; Strobel, S	A novel model of sensitization and oral tolerance to peanut protein		IMMUNOLOGY	sensitization; oral tolerance; peanut; allergy	IMMUNE-RESPONSES; T-CELLS; ATOPIC-DERMATITIS; SUPPRESSION; ALLERGEN; PREVALENCE; ANTIGENS; IDENTIFICATION; INDUCTION; OVALBUMIN	The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens.	28	73	2004	11	10.1111/j.1365-2567.2004.01989.x	Immunology
Sustained increases in numbers of pulmonary dendritic cells after respiratory syncytial virus infection. Background: Respiratory syncytial virus (RSV) bronchiolitis in infants can lead to wheezing and early allergic sensitization. In mice, RSV infection enhances allergic airway inflammation and airway hyperresponsiveness. Dendritic cells are critical in inducing T-cell responses to both viruses and allergens and could be pivotal in regulating interactions between these. Objective: This study addresses the effects of RSV infection on phenotype and function of pulmonary dendritic cells. Methods: BALB/c mice were infected with RSV, and expression of CD11c, MHC II, and CD86 on lung and spleen cells was monitored by flow cytometry for 21 days after infection. CD11c(+) cells were isolated to assess their phagocytic capacity and their ability to induce proliferation in allogenic T cells. Results: Numbers of pulmonary CD11c(+) MHC IIhi cells increased 13-fold starting from day 6 after RSV infection. This was associated with increased CD86 expression, reduced phagocytosis, and increased allogenic T-cell stimulatory capacity in CD11c(+) cells. These changes in the lung outlasted acute infection and were not observed in spleens. Conclusion: RSV infection results in sustained increases in numbers of mature dendritic cells in the lung. These might well contribute to the development of intense airway inflammation and airway hyperresponsiveness after RSV infection and to enhancement of subsequent responses to allergen exposure.. respiratory syncytial virus| antigen-presenting cells| dendritic cells| cd11c antigen| airway inflammation| mice| virus-induced asthma|colony-stimulating factor| antigen-presenting cells| t-cells| airway sensitization| allergic sensitization| immune-response| mice| macrophage| hyperresponsiveness| expression.	JAN-2004	respiratory syncytial virus| antigen-presenting cells| dendritic cells| cd11c antigen| airway inflammation| mice| virus-induced asthma|colony-stimulating factor| antigen-presenting cells| t-cells| airway sensitization| allergic sensitization| immune-response| mice| macrophage| hyperresponsiveness| expression	Beyer, M; Bartz, H; Horner, K; Doths, S; Koerner-Rettberg, C; Schwarze, J	Sustained increases in numbers of pulmonary dendritic cells after respiratory syncytial virus infection		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	respiratory syncytial virus; antigen-presenting cells; dendritic cells; CD11c antigen; airway inflammation; mice; virus-induced asthma	COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; T-CELLS; AIRWAY SENSITIZATION; ALLERGIC SENSITIZATION; IMMUNE-RESPONSE; MICE; MACROPHAGE; HYPERRESPONSIVENESS; EXPRESSION	Background: Respiratory syncytial virus (RSV) bronchiolitis in infants can lead to wheezing and early allergic sensitization. In mice, RSV infection enhances allergic airway inflammation and airway hyperresponsiveness. Dendritic cells are critical in inducing T-cell responses to both viruses and allergens and could be pivotal in regulating interactions between these. Objective: This study addresses the effects of RSV infection on phenotype and function of pulmonary dendritic cells. Methods: BALB/c mice were infected with RSV, and expression of CD11c, MHC II, and CD86 on lung and spleen cells was monitored by flow cytometry for 21 days after infection. CD11c(+) cells were isolated to assess their phagocytic capacity and their ability to induce proliferation in allogenic T cells. Results: Numbers of pulmonary CD11c(+) MHC IIhi cells increased 13-fold starting from day 6 after RSV infection. This was associated with increased CD86 expression, reduced phagocytosis, and increased allogenic T-cell stimulatory capacity in CD11c(+) cells. These changes in the lung outlasted acute infection and were not observed in spleens. Conclusion: RSV infection results in sustained increases in numbers of mature dendritic cells in the lung. These might well contribute to the development of intense airway inflammation and airway hyperresponsiveness after RSV infection and to enhancement of subsequent responses to allergen exposure.	37	73	2004	7	10.1016/j.jaci.2004.10.057	Allergy; Immunology
Relevance of casual contact with peanut butter in children with peanut allergy. Background: Casual skin contact or inhalation of peanut butter fumes is reported and feared to cause allergic reactions in highly sensitive children with peanut allergy but has not been systematically studied. Objective: We sought to determine the clinical relevance of exposure to peanut butter by means of inhalation and skin contact in children with peanut allergy. Methods: Children with significant peanut allergy (recent peanut-specific IgE antibody concentration >50 kIU/L or evidence of peanut-specific IgE antibody and one of the following: clinical anaphylaxis, a reported inhalation-contact reaction, or positive double-blind, placebo-controlled oral challenge result to peanut) underwent double-blind, placebo-controlled, randomized exposures to peanut butter by means of contact with intact skin (0.2 mL pressed flat for 1 minute) and inhalation (surface area of 6.3 square inches 12 inches from the face for 10 minutes). Placebo challenges were performed by using soy butter mixed with histamine (contact), and scent was masked with soy butter, tuna, and mint (inhalation). Results: Thirty children underwent the challenges (median age, 7.7 years; median peanut IgE level, >100 kIU/L; 13 with prior history of contact and 11 with inhalation reactions). None experienced a systemic or respiratory reaction. Erythema (3 subjects), pruritus without erythema (5 subjects), and wheat-and-flare reactions (2 subjects) developed only at the site of skin contact with peanut butter. From this number of participants, it can be stated with 96% confidence that at least 90% of highly sensitive children with peanut allergy would not experience a systemic-respiratory reaction from casual exposure to peanut butter. Conclusions: Casual exposure to peanut butter is unlikely to elicit significant allergic reactions. The results cannot be generalized to larger exposures or to contact with peanut in other forms (flour and roasted peanuts).. peanut allergy| inhalation| skin contact|tree-nut-allergy| natural-history| food allergies| ige| immunotherapy| registry| tests.	JUL-2003	peanut allergy| inhalation| skin contact|tree-nut-allergy| natural-history| food allergies| ige| immunotherapy| registry| tests	Simonte, SJ; Ma, SH; Mofidi, S; Sicherer, SH	Relevance of casual contact with peanut butter in children with peanut allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	peanut allergy; inhalation; skin contact	TREE-NUT-ALLERGY; NATURAL-HISTORY; FOOD ALLERGIES; IGE; IMMUNOTHERAPY; REGISTRY; TESTS	Background: Casual skin contact or inhalation of peanut butter fumes is reported and feared to cause allergic reactions in highly sensitive children with peanut allergy but has not been systematically studied. Objective: We sought to determine the clinical relevance of exposure to peanut butter by means of inhalation and skin contact in children with peanut allergy. Methods: Children with significant peanut allergy (recent peanut-specific IgE antibody concentration >50 kIU/L or evidence of peanut-specific IgE antibody and one of the following: clinical anaphylaxis, a reported inhalation-contact reaction, or positive double-blind, placebo-controlled oral challenge result to peanut) underwent double-blind, placebo-controlled, randomized exposures to peanut butter by means of contact with intact skin (0.2 mL pressed flat for 1 minute) and inhalation (surface area of 6.3 square inches 12 inches from the face for 10 minutes). Placebo challenges were performed by using soy butter mixed with histamine (contact), and scent was masked with soy butter, tuna, and mint (inhalation). Results: Thirty children underwent the challenges (median age, 7.7 years; median peanut IgE level, >100 kIU/L; 13 with prior history of contact and 11 with inhalation reactions). None experienced a systemic or respiratory reaction. Erythema (3 subjects), pruritus without erythema (5 subjects), and wheat-and-flare reactions (2 subjects) developed only at the site of skin contact with peanut butter. From this number of participants, it can be stated with 96% confidence that at least 90% of highly sensitive children with peanut allergy would not experience a systemic-respiratory reaction from casual exposure to peanut butter. Conclusions: Casual exposure to peanut butter is unlikely to elicit significant allergic reactions. The results cannot be generalized to larger exposures or to contact with peanut in other forms (flour and roasted peanuts).	21	73	2003	3	10.1067/mai.2003.1486	Allergy; Immunology
Isolation and characterization of a novel eosinophil-specific galectin released into the lungs in response to allergen challenge. A novel galectin cDNA (galectin-14) was cloned from ovine eosinophil-rich leukocytes by low stringency reverse transcriptase-PCR and cDNA library screening. Data base searches indicate that this gene encodes a novel prototype galectin that contains one putative carbohydrate recognition domain and exhibits most identity to galectin-9/ecalectin, a potent eosinophil chemoattractant. The sugar binding properties of the recombinant molecule were confirmed by a hemagglutination assay and lactose inhibition. The mRNA and protein of galectin-14 are expressed at high levels in eosinophil-rich cell populations. Flow cytometry and cytospot staining demonstrate that the protein localizes to the cytoplasmic, but not the granular, compartment of eosinophils. In contrast, galectin-14 mRNA and protein were not detected in neutrophils, macrophages, or lymphocytes. Western blot analysis of bronchoalveolar lavage fluid indicates that galectin-14 is released from eosinophils into the lumen of the lungs after challenge with house dust mite allergen. The restricted expression of this novel galectin to eosinophils and its release into the lumen of the lung in a sheep asthma model indicates that it may play an important role in eosinophil function and allergic inflammation.. site-directed mutagenesis| thymic epithelial-cells| recombinant galectin-1| extracellular-matrix| molecular-cloning| endogenous lectin| gene-expression| in-vivo| apoptosis| binding.	APR 26-2002	site-directed mutagenesis| thymic epithelial-cells| recombinant galectin-1| extracellular-matrix| molecular-cloning| endogenous lectin| gene-expression| in-vivo| apoptosis| binding	Dunphy, JL; Barcham, GJ; Bischof, RJ; Young, AR; Nash, A; Meeusen, ENT	Isolation and characterization of a novel eosinophil-specific galectin released into the lungs in response to allergen challenge		JOURNAL OF BIOLOGICAL CHEMISTRY		SITE-DIRECTED MUTAGENESIS; THYMIC EPITHELIAL-CELLS; RECOMBINANT GALECTIN-1; EXTRACELLULAR-MATRIX; MOLECULAR-CLONING; ENDOGENOUS LECTIN; GENE-EXPRESSION; IN-VIVO; APOPTOSIS; BINDING	A novel galectin cDNA (galectin-14) was cloned from ovine eosinophil-rich leukocytes by low stringency reverse transcriptase-PCR and cDNA library screening. Data base searches indicate that this gene encodes a novel prototype galectin that contains one putative carbohydrate recognition domain and exhibits most identity to galectin-9/ecalectin, a potent eosinophil chemoattractant. The sugar binding properties of the recombinant molecule were confirmed by a hemagglutination assay and lactose inhibition. The mRNA and protein of galectin-14 are expressed at high levels in eosinophil-rich cell populations. Flow cytometry and cytospot staining demonstrate that the protein localizes to the cytoplasmic, but not the granular, compartment of eosinophils. In contrast, galectin-14 mRNA and protein were not detected in neutrophils, macrophages, or lymphocytes. Western blot analysis of bronchoalveolar lavage fluid indicates that galectin-14 is released from eosinophils into the lumen of the lungs after challenge with house dust mite allergen. The restricted expression of this novel galectin to eosinophils and its release into the lumen of the lung in a sheep asthma model indicates that it may play an important role in eosinophil function and allergic inflammation.	46	73	2002	9	10.1074/jbc.M200214200	Biochemistry & Molecular Biology
Assessment of personal and community-level exposures to particulate matter among children with asthma in Detroit, Michigan, as part of Community Action Against Asthma (CAAA). We report on the research conducted by the Community Action Against Asthma (CAAA) in Detroit, Michigan, to evaluate personal and community-level exposures to particulate matter (PM) among children with asthma living in an urban environment. CAAA is a community-based participatory research collaboration among academia, health agencies, and community-based organizations. CAAA investigates the effects of environmental exposures on the residents of Detroit through a participatory process that engages participants from the affected communities in all aspects of the design and conduct of the research; disseminates the results to all parties involved; and uses the research results to design, in collaboration with all partners, interventions to reduce the identified environmental exposures. The CAAA PM exposure assessment includes four seasonal measurement campaigns each year that are conducted for a 2-week duration each season. In each seasonal measurement period, daily ambient measurements of PM2.5 and PM10 (particulate matter with a mass median aerodynamic diameter less than 2.5 mum and 10 mum, respectively) are collected at two elementary schools in the eastside and southwest communities of Detroit. Concurrently, indoor measurements Of PM2.5 and PM10 are made at the schools as well as inside the homes of a subset of 20 children with asthma. Daily personal exposure measurements of PM10 are also collected for these 20 children with asthma. Results from the first Five seasonal assessment periods reveal that mean personal PM10 (68.4 +/- 39.2 mug/m(3)) and indoor home PM10 (52.2 +/- 30.6 mug/m(3)) exposures are significantly greater (p < 0.05) than the outdoor PM10 concentrations (25.8 +/- 11.8 mug/m(3)). The same was also found for PM2.5 (indoor PM2.5 = 34.4 21.7 mug/m(3); outdoor PM2.5 = 15.6 +/- 8.2 mug/m(3)). In addition, significant differences (p < 0.05) in community-level exposure to both PM10 and PM2.5 are observed between the two Detroit communities (southwest PM10 = 28.9 +/- 14.4 mug/m(3), PM2.5 = 17.0 +/- 9.3 mug/m(3), eastside PM10 = 23.8 +/- 12.1 mug/m(3), PM2.5 = 15.5 +/- 9.0 mug/m(3)). The increased levels in the southwest Detroit community are likely due to the proximity to heavy industrial pollutant point sources and interstate motorways. Trace element characterization of filter samples collected over the 2-year period will allow a more complete assessment of the PM components. When combined with other project measures, including concurrent seasonal twice-daily peak expiratory flow and forced expiratory volume at 1 sec and daily asthma symptom and medication dairies for 300 children with asthma living in the two Detroit communities, these data will allow not only investigations into the sources of PM in the Detroit airshed with regard to PM exposure assessment but also the role of air pollutants in exacerbation of childhood asthma.. ambient pm| childhood asthma| community-based participatory research| particulate matter| personal exposure| urban air quality|emergency room visits| dust mite allergens| air-pollution| hospital admissions| childhood asthma| respiratory-disease| maternal smoking| sulfur-dioxide| public-health| morbidity.	APR-2002	ambient pm| childhood asthma| community-based participatory research| particulate matter| personal exposure| urban air quality|emergency room visits| dust mite allergens| air-pollution| hospital admissions| childhood asthma| respiratory-disease| maternal smoking| sulfur-dioxide| public-health| morbidity	Keeler, GJ; Dvonch, JT; Yip, FY; Parker, EA; Israel, BA; Marsik, FJ; Morishita, M; Barres, JA; Robins, TG; Brakefield-Caldwell, W; Sam, M	Assessment of personal and community-level exposures to particulate matter among children with asthma in Detroit, Michigan, as part of Community Action Against Asthma (CAAA)		ENVIRONMENTAL HEALTH PERSPECTIVES	ambient PM; childhood asthma; community-based participatory research; particulate matter; personal exposure; urban air quality	EMERGENCY ROOM VISITS; DUST MITE ALLERGENS; AIR-POLLUTION; HOSPITAL ADMISSIONS; CHILDHOOD ASTHMA; RESPIRATORY-DISEASE; MATERNAL SMOKING; SULFUR-DIOXIDE; PUBLIC-HEALTH; MORBIDITY	We report on the research conducted by the Community Action Against Asthma (CAAA) in Detroit, Michigan, to evaluate personal and community-level exposures to particulate matter (PM) among children with asthma living in an urban environment. CAAA is a community-based participatory research collaboration among academia, health agencies, and community-based organizations. CAAA investigates the effects of environmental exposures on the residents of Detroit through a participatory process that engages participants from the affected communities in all aspects of the design and conduct of the research; disseminates the results to all parties involved; and uses the research results to design, in collaboration with all partners, interventions to reduce the identified environmental exposures. The CAAA PM exposure assessment includes four seasonal measurement campaigns each year that are conducted for a 2-week duration each season. In each seasonal measurement period, daily ambient measurements of PM2.5 and PM10 (particulate matter with a mass median aerodynamic diameter less than 2.5 mum and 10 mum, respectively) are collected at two elementary schools in the eastside and southwest communities of Detroit. Concurrently, indoor measurements Of PM2.5 and PM10 are made at the schools as well as inside the homes of a subset of 20 children with asthma. Daily personal exposure measurements of PM10 are also collected for these 20 children with asthma. Results from the first Five seasonal assessment periods reveal that mean personal PM10 (68.4 +/- 39.2 mug/m(3)) and indoor home PM10 (52.2 +/- 30.6 mug/m(3)) exposures are significantly greater (p < 0.05) than the outdoor PM10 concentrations (25.8 +/- 11.8 mug/m(3)). The same was also found for PM2.5 (indoor PM2.5 = 34.4 21.7 mug/m(3); outdoor PM2.5 = 15.6 +/- 8.2 mug/m(3)). In addition, significant differences (p < 0.05) in community-level exposure to both PM10 and PM2.5 are observed between the two Detroit communities (southwest PM10 = 28.9 +/- 14.4 mug/m(3), PM2.5 = 17.0 +/- 9.3 mug/m(3), eastside PM10 = 23.8 +/- 12.1 mug/m(3), PM2.5 = 15.5 +/- 9.0 mug/m(3)). The increased levels in the southwest Detroit community are likely due to the proximity to heavy industrial pollutant point sources and interstate motorways. Trace element characterization of filter samples collected over the 2-year period will allow a more complete assessment of the PM components. When combined with other project measures, including concurrent seasonal twice-daily peak expiratory flow and forced expiratory volume at 1 sec and daily asthma symptom and medication dairies for 300 children with asthma living in the two Detroit communities, these data will allow not only investigations into the sources of PM in the Detroit airshed with regard to PM exposure assessment but also the role of air pollutants in exacerbation of childhood asthma.	77	73	2002	9		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. Oxidative stress from ozone (03) exposure augments airway neutrophil recruitment and chemokine production. We and others have shown that severe and sudden asthma is associated with airway neutrophilia, and that 03 oxidative stress is likely to augment neutrophilic airway inflammation in severe asthma. However, very little is known about chemokines that orchestrate oxidative stress-induced neutrophilic airway inflammation in vivo. To identify these chemokines, three groups of BALB/c mice were exposed to sham air, 0.2 ppm O-3, or 0.8 ppm O-3 for 6 h. Compared with sham air, 0.8 ppm O-3, but not 0.2 ppm O-3, induced pronounced neutrophilic airway inflammation that peaked at 18 h postexposure. The 0.8 ppm 03 up-regulated lung mRNA of CXCL1,2,3 (mouse growth-related oncogene-a and macrophage-inflammatory protein-2), CXCL10 (IFN-gamma-inducible protein-10), CCL3 (macrophage-inflammatory protein-1alpha), CCL7 (monocyte chemoattractant protein-3), and CCL11 (eotaxin) at 0 h postexposure, and expression of CXCL10, CCL3, and CCL7 mRNA was sustained 18 h postexposure. 03 increased lung protein levels of CXCL10, CCL7, and CCR3 (CCL7R). The airway epithelium was identified as a source of CCL7. The role of up-regulated chemokines was determined by administering control IgG or IgG Abs against six murine chemokines before 03 exposure. As expected, anti-mouse growth-related oncogene-a inhibited neutrophil recruitment. Surprisingly, Abs to CCL7 and CXCL10 also decreased neutrophil recruitment by 63 and 72%, respectively. These findings indicate that CCL7 and CXCL10, two chemokines not previously reported to orchestrate neutrophilic inflammation, play a critical role in mediating oxidative stress-induced neutrophilic airway inflammation. These observations may have relevance in induction of neutrophilia in severe asthma.. ozone-induced inflammation| obstructive pulmonary-disease| air-pollution| asthmatic subjects| chemoattractant cinc| gene-expression| induced sputum| ifn-gamma| chemokines| hyperresponsiveness.	JAN 15-2002	ozone-induced inflammation| obstructive pulmonary-disease| air-pollution| asthmatic subjects| chemoattractant cinc| gene-expression| induced sputum| ifn-gamma| chemokines| hyperresponsiveness	Michalec, L; Choudhury, BK; Postlethwait, E; Wild, JS; Alam, R; Lett-Brown, M; Sur, S	CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation		JOURNAL OF IMMUNOLOGY		OZONE-INDUCED INFLAMMATION; OBSTRUCTIVE PULMONARY-DISEASE; AIR-POLLUTION; ASTHMATIC SUBJECTS; CHEMOATTRACTANT CINC; GENE-EXPRESSION; INDUCED SPUTUM; IFN-GAMMA; CHEMOKINES; HYPERRESPONSIVENESS	Oxidative stress from ozone (03) exposure augments airway neutrophil recruitment and chemokine production. We and others have shown that severe and sudden asthma is associated with airway neutrophilia, and that 03 oxidative stress is likely to augment neutrophilic airway inflammation in severe asthma. However, very little is known about chemokines that orchestrate oxidative stress-induced neutrophilic airway inflammation in vivo. To identify these chemokines, three groups of BALB/c mice were exposed to sham air, 0.2 ppm O-3, or 0.8 ppm O-3 for 6 h. Compared with sham air, 0.8 ppm O-3, but not 0.2 ppm O-3, induced pronounced neutrophilic airway inflammation that peaked at 18 h postexposure. The 0.8 ppm 03 up-regulated lung mRNA of CXCL1,2,3 (mouse growth-related oncogene-a and macrophage-inflammatory protein-2), CXCL10 (IFN-gamma-inducible protein-10), CCL3 (macrophage-inflammatory protein-1alpha), CCL7 (monocyte chemoattractant protein-3), and CCL11 (eotaxin) at 0 h postexposure, and expression of CXCL10, CCL3, and CCL7 mRNA was sustained 18 h postexposure. 03 increased lung protein levels of CXCL10, CCL7, and CCR3 (CCL7R). The airway epithelium was identified as a source of CCL7. The role of up-regulated chemokines was determined by administering control IgG or IgG Abs against six murine chemokines before 03 exposure. As expected, anti-mouse growth-related oncogene-a inhibited neutrophil recruitment. Surprisingly, Abs to CCL7 and CXCL10 also decreased neutrophil recruitment by 63 and 72%, respectively. These findings indicate that CCL7 and CXCL10, two chemokines not previously reported to orchestrate neutrophilic inflammation, play a critical role in mediating oxidative stress-induced neutrophilic airway inflammation. These observations may have relevance in induction of neutrophilia in severe asthma.	37	73	2002	7		Immunology
Occupational asthma caused by natural rubber latex: Outcome according to cessation or reduction of exposure. Background: The long-term effects of reducing exposure to latex in subjects with latex-induced asthma remain unknown. Objective: The purpose of this study was to compare the health and socioeconomic outcomes of subjects with latex-induced asthma before and after reduction or cessation of exposure to latex. Methods: Thirty-six subjects with latex-induced asthma as ascertained by specific inhalation challenges were investigated after a median follow-up of 56 months (range, 12 to 92 months). Initial and follow-up visits included use of a detailed questionnaire and measurement of the concentration of histamine causing a 20% fall in FEV1 (PC20). At follow-up, information on employment, financial status, and quality of life was collected. Results: At follow-up, 16 subjects were no longer exposed to latex, whereas 20 subjects had reduced exposure. In the subjects who avoided exposure, asthma severity decreased from a median score of 8.5 to 3.5 (P = .001) and the median histamine PC20 value increased from 0.4 mg/mL to 2.3 mg/mL (P = .002). In the subjects who reduced their exposure, asthma-severity score improved from 6.5 to 2.5 (P < .001) and PC20 values rose from 0.5 mg/mL to 2.4 mg/mL (P < .001). Cessation of exposure to latex was associated with asthma-related work disability (69%) and loss of income (62%) more frequently than was reduction of exposure (35% and 30%, respectively). Conclusion: Reduction of exposure to latex should be considered a reasonably safe alternative that is associated with fewer socioeconomic consequences than removal from exposure.. asthma| disability| latex| occupational lung disease|health-care workers| bronchial hyperresponsiveness| toluene diisocyanate| gloves| disability| workplace| impact| cedar.	JAN-2002	asthma| disability| latex| occupational lung disease|health-care workers| bronchial hyperresponsiveness| toluene diisocyanate| gloves| disability| workplace| impact| cedar	Vandenplas, O; Jamart, J; Delwiche, JP; Evrard, G; Larbanois, A	Occupational asthma caused by natural rubber latex: Outcome according to cessation or reduction of exposure		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; disability; latex; occupational lung disease	HEALTH-CARE WORKERS; BRONCHIAL HYPERRESPONSIVENESS; TOLUENE DIISOCYANATE; GLOVES; DISABILITY; WORKPLACE; IMPACT; CEDAR	Background: The long-term effects of reducing exposure to latex in subjects with latex-induced asthma remain unknown. Objective: The purpose of this study was to compare the health and socioeconomic outcomes of subjects with latex-induced asthma before and after reduction or cessation of exposure to latex. Methods: Thirty-six subjects with latex-induced asthma as ascertained by specific inhalation challenges were investigated after a median follow-up of 56 months (range, 12 to 92 months). Initial and follow-up visits included use of a detailed questionnaire and measurement of the concentration of histamine causing a 20% fall in FEV1 (PC20). At follow-up, information on employment, financial status, and quality of life was collected. Results: At follow-up, 16 subjects were no longer exposed to latex, whereas 20 subjects had reduced exposure. In the subjects who avoided exposure, asthma severity decreased from a median score of 8.5 to 3.5 (P = .001) and the median histamine PC20 value increased from 0.4 mg/mL to 2.3 mg/mL (P = .002). In the subjects who reduced their exposure, asthma-severity score improved from 6.5 to 2.5 (P < .001) and PC20 values rose from 0.5 mg/mL to 2.4 mg/mL (P < .001). Cessation of exposure to latex was associated with asthma-related work disability (69%) and loss of income (62%) more frequently than was reduction of exposure (35% and 30%, respectively). Conclusion: Reduction of exposure to latex should be considered a reasonably safe alternative that is associated with fewer socioeconomic consequences than removal from exposure.	26	73	2002	6	10.1067/mai.2002.120760	Allergy; Immunology
The burden of air pollution: Impacts among racial minorities. Various epidemiologic investigations have shown that ambient air pollution levels are associated with acute increases in hospital admissions and mortality in the United States and abroad. The objectives of this investigation were a) to determine if racial minorities are more adversely affected by ambient air pollution than their white counterparts and b) to assess the contribution of socioeconomic status to any observed racial differences in pollution effect. Time-series regression methods were conducted to investigate these hypotheses for daily respiratory hospital admissions in New York City, New York. Pollutants considered included mean daily levels of particulate matter with a mass median aerodynamic diameter less than 10 mum (PM10), ozone (O-3), strong aerosol acidity (H+), and sulfates (SO42). The relative risk for respiratory hospital admission was calculated for each pollutant for a maximum minus mean increment in mean daily pollutant concentration. The greatest difference between the white and nonwhite subgroups was observed for O-3, where the white relative risk (RR) was 1.032 [95% confidence interval (Cl): 0.977-1.089] and the nonwhite RR was 1.122 (95% Cl: 1.074-1.172). Although not statistically different from each other, the various pollutants' RR estimates for the Hispanic nonwhite category in New York City were generally larger in magnitude than those for the non-Hispanic white group. When these analyses incorporated differences in the underlying respiratory hospitalization rates across races (that for nonwhites, was roughly twice that for whites), the disparities in attributable risks from pollution (in terms of excess admissions per day per million persons) were even larger for nonwhites versus whites. However, when insurance status was used as an indicator of socioeconomic/health coverage status, higher RRs were indicated for the poor/working poor (i.e., those on Medicaid and the uninsured) than for those who were economically better off (i.e., the privately insured), even among non-Hispanic whites. Thus, although potential racial differences in pollution exposures could not be explored as a factor, within-race analyses suggested that most of the apparent differences in air pollutant effects found across races were explained by socioeconomic and/or health care disparities.. acidic aerosols| air pollution| epidemiology| ethnicity| ozone| particulate matter| poverty| race| respiratory hospital admissions| socioeconomic status| sulfate| time-series techniques|childhood asthma| new-york| socioeconomic-factors| health| race| hospitalization| prevalence| mortality| poverty| matter.	AUG-2001	acidic aerosols| air pollution| epidemiology| ethnicity| ozone| particulate matter| poverty| race| respiratory hospital admissions| socioeconomic status| sulfate| time-series techniques|childhood asthma| new-york| socioeconomic-factors| health| race| hospitalization| prevalence| mortality| poverty| matter	Gwynn, RC; Thurston, GD	The burden of air pollution: Impacts among racial minorities		ENVIRONMENTAL HEALTH PERSPECTIVES	acidic aerosols; air pollution; epidemiology; ethnicity; ozone; particulate matter; poverty; race; respiratory hospital admissions; socioeconomic status; sulfate; time-series techniques	CHILDHOOD ASTHMA; NEW-YORK; SOCIOECONOMIC-FACTORS; HEALTH; RACE; HOSPITALIZATION; PREVALENCE; MORTALITY; POVERTY; MATTER	Various epidemiologic investigations have shown that ambient air pollution levels are associated with acute increases in hospital admissions and mortality in the United States and abroad. The objectives of this investigation were a) to determine if racial minorities are more adversely affected by ambient air pollution than their white counterparts and b) to assess the contribution of socioeconomic status to any observed racial differences in pollution effect. Time-series regression methods were conducted to investigate these hypotheses for daily respiratory hospital admissions in New York City, New York. Pollutants considered included mean daily levels of particulate matter with a mass median aerodynamic diameter less than 10 mum (PM10), ozone (O-3), strong aerosol acidity (H+), and sulfates (SO42). The relative risk for respiratory hospital admission was calculated for each pollutant for a maximum minus mean increment in mean daily pollutant concentration. The greatest difference between the white and nonwhite subgroups was observed for O-3, where the white relative risk (RR) was 1.032 [95% confidence interval (Cl): 0.977-1.089] and the nonwhite RR was 1.122 (95% Cl: 1.074-1.172). Although not statistically different from each other, the various pollutants' RR estimates for the Hispanic nonwhite category in New York City were generally larger in magnitude than those for the non-Hispanic white group. When these analyses incorporated differences in the underlying respiratory hospitalization rates across races (that for nonwhites, was roughly twice that for whites), the disparities in attributable risks from pollution (in terms of excess admissions per day per million persons) were even larger for nonwhites versus whites. However, when insurance status was used as an indicator of socioeconomic/health coverage status, higher RRs were indicated for the poor/working poor (i.e., those on Medicaid and the uninsured) than for those who were economically better off (i.e., the privately insured), even among non-Hispanic whites. Thus, although potential racial differences in pollution exposures could not be explored as a factor, within-race analyses suggested that most of the apparent differences in air pollutant effects found across races were explained by socioeconomic and/or health care disparities.	24	73	2001	6	10.2307/3454660	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
What establishes a protein as an allergen?. There is little known about the factors that determine the allergenicity of food proteins. Apparently, the ability of a food protein to induce an allergic response requires its presence in substantial amounts in the food supply, its durability during food processing, and its resistance to digestion in the gastrointestinal tract. In addition to the mode and degree of exposure, structural characteristics appear to play an important, role for the capacity of a protein to modulate the immune response towards allergic reactions. Until now, however, there has been no indication for common structural characteristics of linear T cell or linear IgE (B cell) epitopes and the knowledge of structural characteristics of conformational IgE binding sites is very limited. Experimental data point only to certain surface areas of allergenic proteins which are important for IgE binding. Therefore, it is not possible to suggest any structural motif or conformational sequence pattern common to all allergenic proteins. Furthermore, glycosylation appears not to be a common critical determinant of allergenicity since food allergens comprise both glycoproteins and nonglycosylated proteins. Based on the few published three-dimensional structures of allergenic proteins including food proteins, one unifying feature of allergens appears to be their spherical shape. The three-dimensional structures of many more allergens have to be determined, however, to allow for a better understanding of the molecular basis of allergenicity. Most recently, new ideas have been introduced as to why certain biochemical or biologic functions such as enzymatic activities may predispose a protein to become an allergen. Proteolytically active allergens have been demonstrated to irritate the human mucosal surface, to enhance their own transmucosal uptake, and to augment IgE production. Therefore, the functional activity of some allergens may play a role among other factors in the process of sensitization and allergic responses. (C) 2001 Elsevier Science B.V. All rights reserved.. food allergy| proteins|house-dust mite| ige-binding epitopes| bovine beta-lactoglobulin| lipid transfer protein| birch pollen profilin| t-cell epitopes| der-p-i| major allergen| cross-reactivity| x-ray.	MAY 25-2001	food allergy| proteins|house-dust mite| ige-binding epitopes| bovine beta-lactoglobulin| lipid transfer protein| birch pollen profilin| t-cell epitopes| der-p-i| major allergen| cross-reactivity| x-ray	Bredehorst, R; David, K	What establishes a protein as an allergen?		JOURNAL OF CHROMATOGRAPHY B	food allergy; proteins	HOUSE-DUST MITE; IGE-BINDING EPITOPES; BOVINE BETA-LACTOGLOBULIN; LIPID TRANSFER PROTEIN; BIRCH POLLEN PROFILIN; T-CELL EPITOPES; DER-P-I; MAJOR ALLERGEN; CROSS-REACTIVITY; X-RAY	There is little known about the factors that determine the allergenicity of food proteins. Apparently, the ability of a food protein to induce an allergic response requires its presence in substantial amounts in the food supply, its durability during food processing, and its resistance to digestion in the gastrointestinal tract. In addition to the mode and degree of exposure, structural characteristics appear to play an important, role for the capacity of a protein to modulate the immune response towards allergic reactions. Until now, however, there has been no indication for common structural characteristics of linear T cell or linear IgE (B cell) epitopes and the knowledge of structural characteristics of conformational IgE binding sites is very limited. Experimental data point only to certain surface areas of allergenic proteins which are important for IgE binding. Therefore, it is not possible to suggest any structural motif or conformational sequence pattern common to all allergenic proteins. Furthermore, glycosylation appears not to be a common critical determinant of allergenicity since food allergens comprise both glycoproteins and nonglycosylated proteins. Based on the few published three-dimensional structures of allergenic proteins including food proteins, one unifying feature of allergens appears to be their spherical shape. The three-dimensional structures of many more allergens have to be determined, however, to allow for a better understanding of the molecular basis of allergenicity. Most recently, new ideas have been introduced as to why certain biochemical or biologic functions such as enzymatic activities may predispose a protein to become an allergen. Proteolytically active allergens have been demonstrated to irritate the human mucosal surface, to enhance their own transmucosal uptake, and to augment IgE production. Therefore, the functional activity of some allergens may play a role among other factors in the process of sensitization and allergic responses. (C) 2001 Elsevier Science B.V. All rights reserved.	82	73	2001	8	10.1016/S0378-4347(01)00069-X	Biochemistry & Molecular Biology; Chemistry
In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium - A 3-week, randomized, double-blind, within-patient, multicenter study. Study objectives: To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone. Design: A randomized, double-blind, double-dummy, two-period, crossover clinical trial. Setting: Twenty-four clinics and university medical centers in nine countries. Patients: One hundred seventy-two patients with baseline FEV1, less than or equal to 65% predicted, with FEV, reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide. Interventions: Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 mug bid, in addition to ipratropium bromide, 40 mug qid for 3 weeks, followed by salbutamol, 200 mug qid, in addition to ipratropium, 40 mug qid for 3 weeks, or vice versa. Measurements and results: Efficacy end points included morning premedication peak expiratory now (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV, measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV,were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042), The safety profile of the two treatments was comparable. Conclusions: In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.. beta(2)-agonist| copd| formoterol| ipratropium| salbutamol|obstructive pulmonary-disease| air-flow limitation| severe asthma| stable copd| salmeterol| bromide| management| duration| agonist| therapy.	MAY-2001	beta(2)-agonist| copd| formoterol| ipratropium| salbutamol|obstructive pulmonary-disease| air-flow limitation| severe asthma| stable copd| salmeterol| bromide| management| duration| agonist| therapy	D'Urzo, AD; De Salvo, MC; Ramirez-Rivera, A; Almeida, J; Sichletidis, L; Rapatz, G; Kottakis, J	In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium - A 3-week, randomized, double-blind, within-patient, multicenter study		CHEST	beta(2)-agonist; COPD; formoterol; ipratropium; salbutamol	OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW LIMITATION; SEVERE ASTHMA; STABLE COPD; SALMETEROL; BROMIDE; MANAGEMENT; DURATION; AGONIST; THERAPY	Study objectives: To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone. Design: A randomized, double-blind, double-dummy, two-period, crossover clinical trial. Setting: Twenty-four clinics and university medical centers in nine countries. Patients: One hundred seventy-two patients with baseline FEV1, less than or equal to 65% predicted, with FEV, reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide. Interventions: Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 mug bid, in addition to ipratropium bromide, 40 mug qid for 3 weeks, followed by salbutamol, 200 mug qid, in addition to ipratropium, 40 mug qid for 3 weeks, or vice versa. Measurements and results: Efficacy end points included morning premedication peak expiratory now (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV, measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV,were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042), The safety profile of the two treatments was comparable. Conclusions: In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.	34	73	2001	10	10.1378/chest.119.5.1347	General & Internal Medicine; Respiratory System
Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial. Background: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. Methods: We randomly assigned 24 children allergic to grass pollen to receive local allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. Results: The active-treatment group had a statistically significant reduction of total symptoms (P < 0.05), especially bronchial symptoms (P < 0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EGI increased significantly only in the placebo group during natural allergen exposure (P < 0.01). Conclusions: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.. asthma| children| grass pollen| local immunotherapy| rhinitis|eosinophil cationic protein| house dust mite| sublingual immunotherapy| monoclonal-antibodies| standardized grass| hay-fever| rhinitis| asthma| efficacy| extract.	DEC-2000	asthma| children| grass pollen| local immunotherapy| rhinitis|eosinophil cationic protein| house dust mite| sublingual immunotherapy| monoclonal-antibodies| standardized grass| hay-fever| rhinitis| asthma| efficacy| extract	Caffarelli, C; Sensi, LG; Marcucci, F; Cavagni, G	Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial		ALLERGY	asthma; children; grass pollen; local immunotherapy; rhinitis	EOSINOPHIL CATIONIC PROTEIN; HOUSE DUST MITE; SUBLINGUAL IMMUNOTHERAPY; MONOCLONAL-ANTIBODIES; STANDARDIZED GRASS; HAY-FEVER; RHINITIS; ASTHMA; EFFICACY; EXTRACT	Background: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. Methods: We randomly assigned 24 children allergic to grass pollen to receive local allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. Results: The active-treatment group had a statistically significant reduction of total symptoms (P < 0.05), especially bronchial symptoms (P < 0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EGI increased significantly only in the placebo group during natural allergen exposure (P < 0.01). Conclusions: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.	31	73	2000	6	10.1034/j.1398-9995.2000.00655.x	Allergy; Immunology
Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers. Background: The prevalence of allergy to natural rubber latex proteins has increased over recent years among healthcare professionals but also in children undergoing multiple operations. Exposure to the antigen mainly occurs through the respiratory mucosa and the percutaneous route. Clinical manifestations range from urticaria to angioedema, rhinoconjunctivitis, bronchial asthma, or anaphylactic shock. Preventive measures have been proposed to reduce the risk of sensitization by using only powder-free or synthetic gloves and latex-free material in operating units, but this is not always possible. Objective: The aim of this study was to investigate the efficacy and safety of specific immunotherapy in sensitized workers. Methods: Seventeen patients with latex skin allergy and rhinitis (9 of whom also had asthma) were included in this randomized, double-blind, placebo-controlled trial (9 in the active group and 8 in the placebo group) for 1 year. Treatment started with a 2-day course of rush immunotherapy in hospital. Treatment efficacy was assessed after 6 and 12 months by means of symptom and medication scores recorded on diary cards. Conjunctival provocation tests were also performed. Results: Patients in the active treatment group had a significantly tower total rhinitis score after 6 (P < .04) and 12 months (P < .05), conjunctivitis score after 6 months (P < .02), and cutaneous score after 12 months (P < .03) than in the placebo group, Asthma symptoms after 6 or 12 months of treatment were not significantly different between the two groups after adjustment for baseline values. The global medication score was markedly decreased in the latex-treated group. A significant difference in conjunctival reactivity was observed in favor of the active group: the number of patients for whom the threshold dose was increased after 12 months of treatment was significantly greater in the active group than in the placebo group (P < .02). Most injections were well tolerated, but several adverse effects, including hypotension, urticaria, wheezing, and pharyngeal edema, were observed. Conclusion: The clinical benefits observed during the present study included a significant improvement of rhinitis, conjunctivitis, and cutaneous symptoms. Immunotherapy also decreased allergen-specific conjunctival reactivity. Latex-specific immunotherapy may allow sensitized personnel to remain at work, but further trials need to be conducted in a larger number of patients.. latex| urticaria| rhinoconjunctivitis| asthma| anaphylactic shock| specific immunotherapy|natural-rubber latex| cross-reactivity| systemic reactions| hypersensitivity| antibodies| children| antigens| asthma| banana.	SEP-2000	latex| urticaria| rhinoconjunctivitis| asthma| anaphylactic shock| specific immunotherapy|natural-rubber latex| cross-reactivity| systemic reactions| hypersensitivity| antibodies| children| antigens| asthma| banana	Leynadier, F; Herman, D; Vervloet, D; Andre, C	Specific immunotherapy with a standardized latex extract versus placebo in allergic healthcare workers		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	latex; urticaria; rhinoconjunctivitis; asthma; anaphylactic shock; specific immunotherapy	NATURAL-RUBBER LATEX; CROSS-REACTIVITY; SYSTEMIC REACTIONS; HYPERSENSITIVITY; ANTIBODIES; CHILDREN; ANTIGENS; ASTHMA; BANANA	Background: The prevalence of allergy to natural rubber latex proteins has increased over recent years among healthcare professionals but also in children undergoing multiple operations. Exposure to the antigen mainly occurs through the respiratory mucosa and the percutaneous route. Clinical manifestations range from urticaria to angioedema, rhinoconjunctivitis, bronchial asthma, or anaphylactic shock. Preventive measures have been proposed to reduce the risk of sensitization by using only powder-free or synthetic gloves and latex-free material in operating units, but this is not always possible. Objective: The aim of this study was to investigate the efficacy and safety of specific immunotherapy in sensitized workers. Methods: Seventeen patients with latex skin allergy and rhinitis (9 of whom also had asthma) were included in this randomized, double-blind, placebo-controlled trial (9 in the active group and 8 in the placebo group) for 1 year. Treatment started with a 2-day course of rush immunotherapy in hospital. Treatment efficacy was assessed after 6 and 12 months by means of symptom and medication scores recorded on diary cards. Conjunctival provocation tests were also performed. Results: Patients in the active treatment group had a significantly tower total rhinitis score after 6 (P < .04) and 12 months (P < .05), conjunctivitis score after 6 months (P < .02), and cutaneous score after 12 months (P < .03) than in the placebo group, Asthma symptoms after 6 or 12 months of treatment were not significantly different between the two groups after adjustment for baseline values. The global medication score was markedly decreased in the latex-treated group. A significant difference in conjunctival reactivity was observed in favor of the active group: the number of patients for whom the threshold dose was increased after 12 months of treatment was significantly greater in the active group than in the placebo group (P < .02). Most injections were well tolerated, but several adverse effects, including hypotension, urticaria, wheezing, and pharyngeal edema, were observed. Conclusion: The clinical benefits observed during the present study included a significant improvement of rhinitis, conjunctivitis, and cutaneous symptoms. Immunotherapy also decreased allergen-specific conjunctival reactivity. Latex-specific immunotherapy may allow sensitized personnel to remain at work, but further trials need to be conducted in a larger number of patients.	22	73	2000	6		Allergy; Immunology
Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children. We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5 mg/d for 2 d on the bronchoconstriction induced by hyperventilation of cold, dry air in 13 asthmatic children 3 to 5 yr old. The bronchoconstriction was measured as the specific airway resistance (sRaw) in a whole-body plethysmograph before and 4 min after challenge with cold, dry air. The repeatability of the bronchoprotection was examined by repeating the placebo-controlled study in six of the 13 children. sRaw increased by an average of 46% (95% confidence interval [CI]: 30 to 63%) after placebo treatment and 17% (95% CI: 3 to 31%) after montelukast (p < 0.01). Eight of the children were receiving regular treatment with budesonide delivered by an inhaler with a spacer in a mean daily dose of 350 mu g, but the bronchoprotection provided by montelukast was independent of concurrent steroid treatment. There was no convincing evidence of failure to respond, and the protective effect of montelukast was consistent upon repeated testing (p = 0.02). We conclude that the LTRA montelukast provided clinically significant bronchoprotection against the effect of hyperventilation of cold dry air in asthmatic children 3 to 5 yr old. The bronchoprotection appeared to be homogeneous among the children, and seemed independent of steroid treatment. This suggests that LTRAs may be of therapeutic use in limiting clinical symptoms of asthma in young children.. exercise-induced bronchoconstriction| cold dry air| controlled trial| lung-function| inhaled corticosteroids| fluticasone propionate| nebulized budesonide| 14-year-old children| montelukast| challenge.	JUL-2000	exercise-induced bronchoconstriction| cold dry air| controlled trial| lung-function| inhaled corticosteroids| fluticasone propionate| nebulized budesonide| 14-year-old children| montelukast| challenge	Bisgaard, H; Nielsen, KG	Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		EXERCISE-INDUCED BRONCHOCONSTRICTION; COLD DRY AIR; CONTROLLED TRIAL; LUNG-FUNCTION; INHALED CORTICOSTEROIDS; FLUTICASONE PROPIONATE; NEBULIZED BUDESONIDE; 14-YEAR-OLD CHILDREN; MONTELUKAST; CHALLENGE	We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5 mg/d for 2 d on the bronchoconstriction induced by hyperventilation of cold, dry air in 13 asthmatic children 3 to 5 yr old. The bronchoconstriction was measured as the specific airway resistance (sRaw) in a whole-body plethysmograph before and 4 min after challenge with cold, dry air. The repeatability of the bronchoprotection was examined by repeating the placebo-controlled study in six of the 13 children. sRaw increased by an average of 46% (95% confidence interval [CI]: 30 to 63%) after placebo treatment and 17% (95% CI: 3 to 31%) after montelukast (p < 0.01). Eight of the children were receiving regular treatment with budesonide delivered by an inhaler with a spacer in a mean daily dose of 350 mu g, but the bronchoprotection provided by montelukast was independent of concurrent steroid treatment. There was no convincing evidence of failure to respond, and the protective effect of montelukast was consistent upon repeated testing (p = 0.02). We conclude that the LTRA montelukast provided clinically significant bronchoprotection against the effect of hyperventilation of cold dry air in asthmatic children 3 to 5 yr old. The bronchoprotection appeared to be homogeneous among the children, and seemed independent of steroid treatment. This suggests that LTRAs may be of therapeutic use in limiting clinical symptoms of asthma in young children.	31	73	2000	4		General & Internal Medicine; Respiratory System
Antigen-specific responses to diphtheria-tetanus-acellular pertussis vaccine in human infants are initially Th2 polarized. Immune responses to exogenous antigens in infant experimental animals display various degrees of Th2 polarization. Preliminary evidence from small human studies suggest a similar age-dependent response pattern to vaccines, but detailed investigations on vaccine immunity during infancy have not yet been undertaken. We report below the results of a comprehensive prospective study on responses to the tetanus component of the diphtheria, tetanus, acellular pertussis (DTaP) vaccine in a cohort of 55 healthy children, employing peripheral blood mononuclear cells (PBMC) collected at the 2-, 4-, and 6-month vaccinations and at 12 months. Antigen-specific production of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, IL-13, and gamma interferon (IFN-gamma) was determined at each sample point, in parallel with polyclonal (phytohemagglutinin PHA-induced) cytokine responses. Our results indicate early and persistent Th2 responses to the vaccine, in contrast to a more delayed and transient pattern of IFN-gamma production, This initial disparity between the Th1 and Th2 components of the vaccine response was mirrored by patterns of polyclonally induced cytokine production, suggesting that the delayed maturation of the Th1 component of the vaccine response during infancy is secondary to developmental processes occurring within the overall Th cell system.. cell-mediated-immunity| bordetella-pertussis| whole-cell| early-childhood| t-cells| environmental allergens| neonatal tolerance| household exposure| inhalant allergen| controlled trial.	JUL-2000	cell-mediated-immunity| bordetella-pertussis| whole-cell| early-childhood| t-cells| environmental allergens| neonatal tolerance| household exposure| inhalant allergen| controlled trial	Rowe, J; Macaubas, C; Monger, TM; Holt, BJ; Harvey, J; Poolman, JT; Sly, PD; Holt, PG	Antigen-specific responses to diphtheria-tetanus-acellular pertussis vaccine in human infants are initially Th2 polarized		INFECTION AND IMMUNITY		CELL-MEDIATED-IMMUNITY; BORDETELLA-PERTUSSIS; WHOLE-CELL; EARLY-CHILDHOOD; T-CELLS; ENVIRONMENTAL ALLERGENS; NEONATAL TOLERANCE; HOUSEHOLD EXPOSURE; INHALANT ALLERGEN; CONTROLLED TRIAL	Immune responses to exogenous antigens in infant experimental animals display various degrees of Th2 polarization. Preliminary evidence from small human studies suggest a similar age-dependent response pattern to vaccines, but detailed investigations on vaccine immunity during infancy have not yet been undertaken. We report below the results of a comprehensive prospective study on responses to the tetanus component of the diphtheria, tetanus, acellular pertussis (DTaP) vaccine in a cohort of 55 healthy children, employing peripheral blood mononuclear cells (PBMC) collected at the 2-, 4-, and 6-month vaccinations and at 12 months. Antigen-specific production of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, IL-13, and gamma interferon (IFN-gamma) was determined at each sample point, in parallel with polyclonal (phytohemagglutinin PHA-induced) cytokine responses. Our results indicate early and persistent Th2 responses to the vaccine, in contrast to a more delayed and transient pattern of IFN-gamma production, This initial disparity between the Th1 and Th2 components of the vaccine response was mirrored by patterns of polyclonally induced cytokine production, suggesting that the delayed maturation of the Th1 component of the vaccine response during infancy is secondary to developmental processes occurring within the overall Th cell system.	28	73	2000	5	10.1128/IAI.68.7.3873-3877.2000	Immunology; Infectious Diseases
Development of atopy and asthma: Candidate environmental influences and important periods of exposure. Atopy is a major risk factor for the development of asthma. immune processes that lead to the development of antigen-specific IgE are essential to the development of atopy. This review examines the immune processes that are candidate targets for modulation by environmental agents; environmental and lifestyle factors that have been suggested as modulators of the development of atopy; and the impact of known environmental agents on atopic processes in the airway. The most important periods of immune development with regard to expression of atopy are likely during gestation and early childhood. A better understanding of which environmental agents are important, as well as the period of life during which these agents may exert an important effect, is essential to devising rational environmental avoidance strategies for at-risk populations.. asthma| atopy| immunoglobulin e (ige)| immunoglobulin g (igg)| t-helper cell type 1 (th1)| t-helper cell type 2 (th2)|interferon-gamma production| serum ige levels| diesel-exhaust| in-vivo| allergic sensitization| adjuvant activity| immune-responses| risk factor| mice| association.	JUN-2000	asthma| atopy| immunoglobulin e (ige)| immunoglobulin g (igg)| t-helper cell type 1 (th1)| t-helper cell type 2 (th2)|interferon-gamma production| serum ige levels| diesel-exhaust| in-vivo| allergic sensitization| adjuvant activity| immune-responses| risk factor| mice| association	Peden, DB	Development of atopy and asthma: Candidate environmental influences and important periods of exposure		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; atopy; immunoglobulin E (IgE); immunoglobulin G (IgG); T-helper cell type 1 (Th1); T-helper cell type 2 (Th2)	INTERFERON-GAMMA PRODUCTION; SERUM IGE LEVELS; DIESEL-EXHAUST; IN-VIVO; ALLERGIC SENSITIZATION; ADJUVANT ACTIVITY; IMMUNE-RESPONSES; RISK FACTOR; MICE; ASSOCIATION	Atopy is a major risk factor for the development of asthma. immune processes that lead to the development of antigen-specific IgE are essential to the development of atopy. This review examines the immune processes that are candidate targets for modulation by environmental agents; environmental and lifestyle factors that have been suggested as modulators of the development of atopy; and the impact of known environmental agents on atopic processes in the airway. The most important periods of immune development with regard to expression of atopy are likely during gestation and early childhood. A better understanding of which environmental agents are important, as well as the period of life during which these agents may exert an important effect, is essential to devising rational environmental avoidance strategies for at-risk populations.	59	73	2000	8	10.2307/3454539	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma. Background: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis. Objective: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenge in subjects with atopic asthma. Methods: By using a split-nose randomized crossover design, individual nares of 12 asthmatic subjects underwent challenge and lavage as follows, Immediately after a baseline nasal lavage, one nares received normal saline, and the other received dust mite antigen, Four hours later both nares were exposed to either saline or endotoxin. Dust mite antigen (Dermatophagoides farinae) and endotoxin (Escherichia roll 026:B6) doses were 100 AU and 1000 ng, respectively. Postchallenge lavages were done at 8 and 24 hours after the initial challenge. The subjects then returned a minimum of 3 weeks later for crossover to the study arm. Nasal lavage fluid was analyzed for total and differential cell counts, IL-8, IL-6, intercellular adhesion molecule 1, GM-CSF, eosinophil cationic protein, myeloperoxidase, and soluble CD14. Results: A significant increase in the total inflammatory cell count was seen at 8 hours for the dust mite/endotoxin exposure compared with the saline/saline and saline/endotoxin exposures. Differential cell counts revealed a similar neutrophilic and eosinophilic inflammation for the dust mite/endotoxin exposure at 8 hours. Conclusions: These data demonstrate an interaction between allergen and endotoxin exposure in asthmatic subjects, suggesting that a prior allergen challenge significantly augments the endotoxin-induced inflammation. Moreover, these data provide further evidence that concomitant exposure to allergen and endotoxin may he an important factor in asthma pathogenesis.. endotoxin| dust mite| antigen| asthma| eosinophils| neutrophils| allergy|air-pollution| ozone| mortality| challenge| responses| exposure| workers| health.	MAR-2000	endotoxin| dust mite| antigen| asthma| eosinophils| neutrophils| allergy|air-pollution| ozone| mortality| challenge| responses| exposure| workers| health	Eldridge, MW; Peden, DB	Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	endotoxin; dust mite; antigen; asthma; eosinophils; neutrophils; allergy	AIR-POLLUTION; OZONE; MORTALITY; CHALLENGE; RESPONSES; EXPOSURE; WORKERS; HEALTH	Background: Recent epidemiologic and in vivo studies have suggested that inhaled endotoxin plays an important role in asthma pathogenesis. Objective: The present study examines the effect of nasal allergen provocation on subsequent endotoxin challenge in subjects with atopic asthma. Methods: By using a split-nose randomized crossover design, individual nares of 12 asthmatic subjects underwent challenge and lavage as follows, Immediately after a baseline nasal lavage, one nares received normal saline, and the other received dust mite antigen, Four hours later both nares were exposed to either saline or endotoxin. Dust mite antigen (Dermatophagoides farinae) and endotoxin (Escherichia roll 026:B6) doses were 100 AU and 1000 ng, respectively. Postchallenge lavages were done at 8 and 24 hours after the initial challenge. The subjects then returned a minimum of 3 weeks later for crossover to the study arm. Nasal lavage fluid was analyzed for total and differential cell counts, IL-8, IL-6, intercellular adhesion molecule 1, GM-CSF, eosinophil cationic protein, myeloperoxidase, and soluble CD14. Results: A significant increase in the total inflammatory cell count was seen at 8 hours for the dust mite/endotoxin exposure compared with the saline/saline and saline/endotoxin exposures. Differential cell counts revealed a similar neutrophilic and eosinophilic inflammation for the dust mite/endotoxin exposure at 8 hours. Conclusions: These data demonstrate an interaction between allergen and endotoxin exposure in asthmatic subjects, suggesting that a prior allergen challenge significantly augments the endotoxin-induced inflammation. Moreover, these data provide further evidence that concomitant exposure to allergen and endotoxin may he an important factor in asthma pathogenesis.	27	73	2000	7	10.1067/mai.2000.104552	Allergy; Immunology
Phthalate exposure and children's health. Purpose of review Phthalates are multifunctional chemicals used in personal care products, medications, and plastics. We reviewed the epidemiological literature examining the relationship between early life phthalate exposure and pediatric health outcomes. Recent findings Five studies from Asia, Europe, and the United States suggest that childhood exposure to di-2-ethylhexyl phthalate (DEHP) and butylbenzyl phthalate (BBzP) may increase the risk of allergic diseases including asthma and eczema. Six studies from four different prospective cohorts report that gestational BBzP, DEHP, di-butyl phthalate (DBP), and di-ethyl phthalate (DEP) exposures are associated with alterations in infant/toddler physical development as well as parent-reported externalizing, internalizing, and autistic-like child behavior. However, there are inconsistencies related to the specific phthalates and behavioral domains. Two small studies report shorter anogenital distance among male infants with higher gestational phthalate exposure. Summary Several epidemiological studies suggest fetal and childhood exposure to some phthalates may perturb normal development, with several studies consistently reporting increased risk of allergic diseases with DEHP and BBzP exposure. Although anticipatory guidance is not evidence-based at this time, providers can counsel concerned patients to reduce phthalate exposures in order to protect the developing fetus and child from potential adverse health outcomes.. children| endocrine disruption| epidemiology| phthalates|in-utero exposure| body topical application| personal care products| school-age-children| new-york-city| urinary concentrations| prenatal exposure| bisphenol-a| diethylhexyl phthalate| di(2-ethylhexyl)phthalate dehp.	APR-2013	children| endocrine disruption| epidemiology| phthalates|in-utero exposure| body topical application| personal care products| school-age-children| new-york-city| urinary concentrations| prenatal exposure| bisphenol-a| diethylhexyl phthalate| di(2-ethylhexyl)phthalate dehp	Braun, JM; Sathyanarayana, S; Hauser, R	Phthalate exposure and children's health		CURRENT OPINION IN PEDIATRICS	children; endocrine disruption; epidemiology; phthalates	IN-UTERO EXPOSURE; BODY TOPICAL APPLICATION; PERSONAL CARE PRODUCTS; SCHOOL-AGE-CHILDREN; NEW-YORK-CITY; URINARY CONCENTRATIONS; PRENATAL EXPOSURE; BISPHENOL-A; DIETHYLHEXYL PHTHALATE; DI(2-ETHYLHEXYL)PHTHALATE DEHP	Purpose of review Phthalates are multifunctional chemicals used in personal care products, medications, and plastics. We reviewed the epidemiological literature examining the relationship between early life phthalate exposure and pediatric health outcomes. Recent findings Five studies from Asia, Europe, and the United States suggest that childhood exposure to di-2-ethylhexyl phthalate (DEHP) and butylbenzyl phthalate (BBzP) may increase the risk of allergic diseases including asthma and eczema. Six studies from four different prospective cohorts report that gestational BBzP, DEHP, di-butyl phthalate (DBP), and di-ethyl phthalate (DEP) exposures are associated with alterations in infant/toddler physical development as well as parent-reported externalizing, internalizing, and autistic-like child behavior. However, there are inconsistencies related to the specific phthalates and behavioral domains. Two small studies report shorter anogenital distance among male infants with higher gestational phthalate exposure. Summary Several epidemiological studies suggest fetal and childhood exposure to some phthalates may perturb normal development, with several studies consistently reporting increased risk of allergic diseases with DEHP and BBzP exposure. Although anticipatory guidance is not evidence-based at this time, providers can counsel concerned patients to reduce phthalate exposures in order to protect the developing fetus and child from potential adverse health outcomes.	75	72	2013	8	10.1097/MOP.0b013e32835e1eb6	Pediatrics
The Relationship Between Trees and Human Health Evidence from the Spread of the Emerald Ash Borer. Background: Several recent studies have identified a relationship between the natural environment and improved health outcomes. However, for practical reasons, most have been observational, cross-sectional studies. Purpose: A natural experiment, which provides stronger evidence of causality, was used to test whether a major change to the natural environment-the loss of 100 million trees to the emerald ash borer, an invasive forest pest-has influenced mortality related to cardiovascular and lower-respiratory diseases. Methods: Two fixed-effects regression models were used to estimate the relationship between emerald ash borer presence and county-level mortality from 1990 to 2007 in 15 U. S. states, while controlling for a wide range of demographic covariates. Data were collected from 1990 to 2007, and the analyses were conducted in 2011 and 2012. Results: There was an increase in mortality related to cardiovascular and lower-respiratory-tract illness in counties infested with the emerald ash borer. The magnitude of this effect was greater as infestation progressed and in counties with above-average median household income. Across the 15 states in the study area, the borer was associated with an additional 6113 deaths related to illness of the lower respiratory system, and 15,080 cardiovascular-related deaths. Conclusions: Results suggest that loss of trees to the emerald ash borer increased mortality related to cardiovascular and lower-respiratory-tract illness. This finding adds to the growing evidence that the natural environment provides major public health benefits. (Am J Prev Med 2013; 44(2): 139-145) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine. physical-activity| street trees| green space| asthma| inequalities| mortality| exposure| disease| forest| areas.	FEB-2013	physical-activity| street trees| green space| asthma| inequalities| mortality| exposure| disease| forest| areas	Donovan, GH; Butry, DT; Michael, YL; Prestemon, JP; Liebhold, AM; Gatziolis, D; Mao, MY	The Relationship Between Trees and Human Health Evidence from the Spread of the Emerald Ash Borer		AMERICAN JOURNAL OF PREVENTIVE MEDICINE		PHYSICAL-ACTIVITY; STREET TREES; GREEN SPACE; ASTHMA; INEQUALITIES; MORTALITY; EXPOSURE; DISEASE; FOREST; AREAS	Background: Several recent studies have identified a relationship between the natural environment and improved health outcomes. However, for practical reasons, most have been observational, cross-sectional studies. Purpose: A natural experiment, which provides stronger evidence of causality, was used to test whether a major change to the natural environment-the loss of 100 million trees to the emerald ash borer, an invasive forest pest-has influenced mortality related to cardiovascular and lower-respiratory diseases. Methods: Two fixed-effects regression models were used to estimate the relationship between emerald ash borer presence and county-level mortality from 1990 to 2007 in 15 U. S. states, while controlling for a wide range of demographic covariates. Data were collected from 1990 to 2007, and the analyses were conducted in 2011 and 2012. Results: There was an increase in mortality related to cardiovascular and lower-respiratory-tract illness in counties infested with the emerald ash borer. The magnitude of this effect was greater as infestation progressed and in counties with above-average median household income. Across the 15 states in the study area, the borer was associated with an additional 6113 deaths related to illness of the lower respiratory system, and 15,080 cardiovascular-related deaths. Conclusions: Results suggest that loss of trees to the emerald ash borer increased mortality related to cardiovascular and lower-respiratory-tract illness. This finding adds to the growing evidence that the natural environment provides major public health benefits. (Am J Prev Med 2013; 44(2): 139-145) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine	37	72	2013	7	10.1016/j.amepre.2012.09.066	Public, Environmental & Occupational Health; General & Internal Medicine
High concentrations of biological aerosol particles and ice nuclei during and after rain. Bioaerosols are relevant for public health and may play an important role in the climate system, but their atmospheric abundance, properties, and sources are not well understood. Here we show that the concentration of airborne biological particles in a North American forest ecosystem increases significantly during rain and that bioparticles are closely correlated with atmospheric ice nuclei (IN). The greatest increase of bioparticles and IN occurred in the size range of 2-6 mu m, which is characteristic for bacterial aggregates and fungal spores. By DNA analysis we found high diversities of airborne bacteria and fungi, including groups containing human and plant pathogens (mildew, smut and rust fungi, molds, Enterobacteriaceae, Pseudomonadaceae). In addition to detecting known bacterial and fungal IN (Pseudomonas sp., Fusarium sporotrichioides), we discovered two species of IN-active fungi that were not previously known as biological ice nucleators (Isaria farinosa and Acremonium implicatum). Our findings suggest that atmospheric bioaerosols, IN, and rainfall are more tightly coupled than previously assumed.. nucleation-active bacteria| mineral dust particles| fungal spores| pseudomonas-syringae| atmospheric aerosols| thunderstorm asthma| size distributions| airborne bacteria| splash dispersal| uv-aps.	2013	nucleation-active bacteria| mineral dust particles| fungal spores| pseudomonas-syringae| atmospheric aerosols| thunderstorm asthma| size distributions| airborne bacteria| splash dispersal| uv-aps	Huffman, JA; Prenni, AJ; DeMott, PJ; Pohlker, C; Mason, RH; Robinson, NH; Frohlich-Nowoisky, J; Tobo, Y; Despres, VR; Garcia, E; Gochis, DJ; Harris, E; Mueller-Germann, I; Ruzene, C; Schmer, B; Sinha, B; Day, DA; Andreae, MO; Jimenez, JL; Gallagher, M; Kreidenweis, SM; Bertram, AK; Poschl, U	High concentrations of biological aerosol particles and ice nuclei during and after rain		ATMOSPHERIC CHEMISTRY AND PHYSICS		NUCLEATION-ACTIVE BACTERIA; MINERAL DUST PARTICLES; FUNGAL SPORES; PSEUDOMONAS-SYRINGAE; ATMOSPHERIC AEROSOLS; THUNDERSTORM ASTHMA; SIZE DISTRIBUTIONS; AIRBORNE BACTERIA; SPLASH DISPERSAL; UV-APS	Bioaerosols are relevant for public health and may play an important role in the climate system, but their atmospheric abundance, properties, and sources are not well understood. Here we show that the concentration of airborne biological particles in a North American forest ecosystem increases significantly during rain and that bioparticles are closely correlated with atmospheric ice nuclei (IN). The greatest increase of bioparticles and IN occurred in the size range of 2-6 mu m, which is characteristic for bacterial aggregates and fungal spores. By DNA analysis we found high diversities of airborne bacteria and fungi, including groups containing human and plant pathogens (mildew, smut and rust fungi, molds, Enterobacteriaceae, Pseudomonadaceae). In addition to detecting known bacterial and fungal IN (Pseudomonas sp., Fusarium sporotrichioides), we discovered two species of IN-active fungi that were not previously known as biological ice nucleators (Isaria farinosa and Acremonium implicatum). Our findings suggest that atmospheric bioaerosols, IN, and rainfall are more tightly coupled than previously assumed.	89	72	2013	14	10.5194/acp-13-6151-2013	Meteorology & Atmospheric Sciences
Determinants of asthma after severe respiratory syncytial virus bronchiolitis. Background: The development of asthma after respiratory syncytial virus (RSV) bronchiolitis has been demonstrated in case-control studies, although the determinants of post-RSV asthma remain undefined. Objectives: We sought to evaluate the potential determinants of physician-diagnosed asthma after severe RSV bronchiolitis during infancy. Methods: We enrolled 206 children during an initial episode of severe RSV bronchiolitis at 12 months of age or less in a prospective cohort study and followed these children for up to 6 years. In a subset of 81 children, we analyzed CCL5 (RANTES) mRNA expression in upper airway epithelial cells. Results: Forty-eight percent of children had physician-diagnosed asthma before the seventh birthday. Independent determinants significantly associated with increased risk for physician-diagnosed asthma by the seventh birthday included maternal asthma (odds ratio [OR], 5.2; 95% CI, 1.7-15.9; P = .004), exposure to high levels of dog allergen (OR, 3.2; 95% CI, 1.3-7.7; P = .012), aeroallergen sensitivity at age 3 years (OR, 10.7; 95% CI, 2.1-55.0; P = .005), recurrent wheezing during the first 3 years of life (OR, 7.3; 95% CI, 1.2-43.3; P = .028), and CCL5 expression in nasal epithelia during acute RSV infection (OR, 3.8; 95% CI, 1.2-2.4; P < .001). White children (OR, 0.19; 95% CI, 0.04-0.93; P = .041) and children attending day care (OR, 0.18; 95% CI, 0.04-0.84; P = .029) had a decreased risk of physician-diagnosed asthma. Conclusions: Approximately 50% of children who experience severe RSV bronchiolitis have a subsequent asthma diagnosis. The presence of increased CCL5 levels in nasal epithelia at the time of bronchiolitis or the development of allergic sensitization by age 3 years are associated with increased likelihood of subsequent asthma. (J Allergy Clin Immunol 2012;130:91-100.). bronchiolitis| respiratory syncytial virus| asthma| prospective cohort| ccl5|longitudinal birth-cohort| day-care attendance| early-childhood| early-life| rsv bronchiolitis| allergic sensitization| parental history| diagnosed asthma| young-children| 1st year.	JUL-2012	bronchiolitis| respiratory syncytial virus| asthma| prospective cohort| ccl5|longitudinal birth-cohort| day-care attendance| early-childhood| early-life| rsv bronchiolitis| allergic sensitization| parental history| diagnosed asthma| young-children| 1st year	Bacharier, LB; Cohen, R; Schweiger, T; Yin-DeClue, H; Christie, C; Zheng, J; Schechtman, KB; Strunk, RC; Castro, M	Determinants of asthma after severe respiratory syncytial virus bronchiolitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Bronchiolitis; respiratory syncytial virus; asthma; prospective cohort; CCL5	LONGITUDINAL BIRTH-COHORT; DAY-CARE ATTENDANCE; EARLY-CHILDHOOD; EARLY-LIFE; RSV BRONCHIOLITIS; ALLERGIC SENSITIZATION; PARENTAL HISTORY; DIAGNOSED ASTHMA; YOUNG-CHILDREN; 1ST YEAR	Background: The development of asthma after respiratory syncytial virus (RSV) bronchiolitis has been demonstrated in case-control studies, although the determinants of post-RSV asthma remain undefined. Objectives: We sought to evaluate the potential determinants of physician-diagnosed asthma after severe RSV bronchiolitis during infancy. Methods: We enrolled 206 children during an initial episode of severe RSV bronchiolitis at 12 months of age or less in a prospective cohort study and followed these children for up to 6 years. In a subset of 81 children, we analyzed CCL5 (RANTES) mRNA expression in upper airway epithelial cells. Results: Forty-eight percent of children had physician-diagnosed asthma before the seventh birthday. Independent determinants significantly associated with increased risk for physician-diagnosed asthma by the seventh birthday included maternal asthma (odds ratio [OR], 5.2; 95% CI, 1.7-15.9; P = .004), exposure to high levels of dog allergen (OR, 3.2; 95% CI, 1.3-7.7; P = .012), aeroallergen sensitivity at age 3 years (OR, 10.7; 95% CI, 2.1-55.0; P = .005), recurrent wheezing during the first 3 years of life (OR, 7.3; 95% CI, 1.2-43.3; P = .028), and CCL5 expression in nasal epithelia during acute RSV infection (OR, 3.8; 95% CI, 1.2-2.4; P < .001). White children (OR, 0.19; 95% CI, 0.04-0.93; P = .041) and children attending day care (OR, 0.18; 95% CI, 0.04-0.84; P = .029) had a decreased risk of physician-diagnosed asthma. Conclusions: Approximately 50% of children who experience severe RSV bronchiolitis have a subsequent asthma diagnosis. The presence of increased CCL5 levels in nasal epithelia at the time of bronchiolitis or the development of allergic sensitization by age 3 years are associated with increased likelihood of subsequent asthma. (J Allergy Clin Immunol 2012;130:91-100.)	52	72	2012	13	10.1016/j.jaci.2012.02.010	Allergy; Immunology
Ventilation in European dwellings: A review. Adequate ventilation is essential for the health and comfort of building occupants. This review examines, first of all, why residential ventilation is an issue of concern in Europe and how is related to the human health. A review of the current status of residential ventilation standards and regulations in Europe is also provided, as a reference. Finally, a review of measurements of ventilation rates in European dwellings is provided, where the compatibility with the European standards/regulations is examined. The review shows that ventilation is increasingly becoming recognised as an important component of a healthy dwelling. Ventilation requirements receive major attention in building regulations, across Europe. However, ventilation measurements across Europe show that ventilation is in practice often poor, resulting in reduced ventilation rates (lower than 0.5 h(-1), which is currently a standard in many European countries), increased concentrations of indoor pollutants and hence exposure to health risk. Surveys showed that although occupants generally think that ventilation is important, their understanding of the ventilation systems in their own houses is low, resulting to under-ventilated homes. (C) 2011 Elsevier Ltd. All rights reserved.. ventilation| rates| regulations| health|volatile organic-compounds| indoor air-quality| house-dust| building characteristics| mechanical ventilation| allergic sensitization| catalan dwellings| young-children| mite allergen| long-term.	JAN-2012	ventilation| rates| regulations| health|volatile organic-compounds| indoor air-quality| house-dust| building characteristics| mechanical ventilation| allergic sensitization| catalan dwellings| young-children| mite allergen| long-term	Dimitroulopoulou, C	Ventilation in European dwellings: A review		BUILDING AND ENVIRONMENT	Ventilation; Rates; Regulations; Health	VOLATILE ORGANIC-COMPOUNDS; INDOOR AIR-QUALITY; HOUSE-DUST; BUILDING CHARACTERISTICS; MECHANICAL VENTILATION; ALLERGIC SENSITIZATION; CATALAN DWELLINGS; YOUNG-CHILDREN; MITE ALLERGEN; LONG-TERM	Adequate ventilation is essential for the health and comfort of building occupants. This review examines, first of all, why residential ventilation is an issue of concern in Europe and how is related to the human health. A review of the current status of residential ventilation standards and regulations in Europe is also provided, as a reference. Finally, a review of measurements of ventilation rates in European dwellings is provided, where the compatibility with the European standards/regulations is examined. The review shows that ventilation is increasingly becoming recognised as an important component of a healthy dwelling. Ventilation requirements receive major attention in building regulations, across Europe. However, ventilation measurements across Europe show that ventilation is in practice often poor, resulting in reduced ventilation rates (lower than 0.5 h(-1), which is currently a standard in many European countries), increased concentrations of indoor pollutants and hence exposure to health risk. Surveys showed that although occupants generally think that ventilation is important, their understanding of the ventilation systems in their own houses is low, resulting to under-ventilated homes. (C) 2011 Elsevier Ltd. All rights reserved.	96	72	2012	17	10.1016/j.buildenv.2011.07.016	Construction & Building Technology; Engineering
Evidence for Family-Centered Care for Children With Special Health Care Needs: A Systematic Review. OBJECTIVE: Family-centered care (FCC) has received widespread endorsement for use in care in the United States. In this study, we conducted a systematic review of evidence for FCC focusing specifically on family-provider partnership as the activity that constitutes FCC. METHODS: We found and reviewed articles from the medical, nursing, psychology, and sociology literature spanning 1986 to 2010. We also reviewed articles obtained through related references and through recommendations from key informants. Four sets of terms were used to search, including FCC, child/adolescent, children with special health care needs (CSHCN, defined broadly or by condition), and a relevant outcome. RESULTS: Twenty-four studies met the review criteria. Eight were cross-sectional studies from the National Survey of Children With Special Health Care Needs, and 7 were reports of randomized, controlled trials. Of the 24 articles reviewed, 13 examined populations of CSHCN or similar populations, 6 examined children with asthma, and the remaining studied children with other specific conditions. We found positive associations of FCC with improvements in efficient use of services, health status, satisfaction, access to care, communication, systems of care, family functioning, and family impact/cost. There was little available evidence, however, for some outcomes, including cost and transition. CONCLUSIONS: The available evidence suggests that FCC is associated with improved outcomes for CSHCN. With positive findings for most of the studies reviewed here and the compelling arguments for FCC, we recommend the use of this approach by individuals and organizations.. children with special health care needs| family-centered care|medical home| national-survey| mental-health| asthma| services| outcomes| satisfaction| physicians| insurance| education.	MAR-APR-2011	children with special health care needs| family-centered care|medical home| national-survey| mental-health| asthma| services| outcomes| satisfaction| physicians| insurance| education	Kuhlthau, KA; Bloom, S; Van Cleave, J; Knapp, AA; Romm, D; Klatka, K; Homer, CJ; Newacheck, PW; Perrin, JM	Evidence for Family-Centered Care for Children With Special Health Care Needs: A Systematic Review		ACADEMIC PEDIATRICS	children with special health care needs; family-centered care	MEDICAL HOME; NATIONAL-SURVEY; MENTAL-HEALTH; ASTHMA; SERVICES; OUTCOMES; SATISFACTION; PHYSICIANS; INSURANCE; EDUCATION	OBJECTIVE: Family-centered care (FCC) has received widespread endorsement for use in care in the United States. In this study, we conducted a systematic review of evidence for FCC focusing specifically on family-provider partnership as the activity that constitutes FCC. METHODS: We found and reviewed articles from the medical, nursing, psychology, and sociology literature spanning 1986 to 2010. We also reviewed articles obtained through related references and through recommendations from key informants. Four sets of terms were used to search, including FCC, child/adolescent, children with special health care needs (CSHCN, defined broadly or by condition), and a relevant outcome. RESULTS: Twenty-four studies met the review criteria. Eight were cross-sectional studies from the National Survey of Children With Special Health Care Needs, and 7 were reports of randomized, controlled trials. Of the 24 articles reviewed, 13 examined populations of CSHCN or similar populations, 6 examined children with asthma, and the remaining studied children with other specific conditions. We found positive associations of FCC with improvements in efficient use of services, health status, satisfaction, access to care, communication, systems of care, family functioning, and family impact/cost. There was little available evidence, however, for some outcomes, including cost and transition. CONCLUSIONS: The available evidence suggests that FCC is associated with improved outcomes for CSHCN. With positive findings for most of the studies reviewed here and the compelling arguments for FCC, we recommend the use of this approach by individuals and organizations.	39	72	2011	8		Pediatrics
Tobacco-Smoke Exposure in Children Who Live in Multiunit Housing. OBJECTIVE: There is no safe level of secondhand tobacco-smoke exposure, and no previous studies have explored multiunit housing as a potential contributor to secondhand tobacco-smoke exposure in children. We hypothesized that children who live in apartments have higher cotinine levels than those who live in detached homes, when controlling for demographics. METHODS: We analyzed data from the 2001-2006 National Health and Nutrition Examination Survey. The housing types we included in our study were detached houses (including mobile homes), attached houses, and apartments. Our study subjects were children between the ages of 6 and 18 years. Cotinine levels were used to assess secondhand tobacco-smoke exposure, and those living with someone who smoked inside the home were excluded. chi(2) tests, t tests, and Tobit regression models were used in Stata. Sample weights accounted for the complex survey design. RESULTS: Of 5002 children in our study, 73% were exposed to secondhand tobacco smoke. Children living in apartments had an increase in cotinine of 45% over those living in detached houses. This increase was 212% (P < .01) for white residents and 46% (P < .03) for black residents, but there was no significant increase for those of other races/ethnicities. At every cutoff level of cotinine, children in apartments had higher rates of exposure. The exposure effect of housing type was most pronounced at lower levels of cotinine. CONCLUSIONS: Most children without known secondhand tobacco-smoke exposure inside the home still showed evidence of tobacco-smoke exposure. Children in apartments had higher mean cotinine levels than children in detached houses. Potential causes for this result could be seepage through walls or shared ventilation systems. Smoking bans in multiunit housing may reduce children's exposure to tobacco smoke. Pediatrics 2011;127:85-92. secondhand smoke| passive smoking| environmental tobacco smoke| multiunit housing| apartment|secondhand smoke| thirdhand-smoke| united-states| us children| nicotine| association| asthma| home| adolescents| dust.	JAN-2011	secondhand smoke| passive smoking| environmental tobacco smoke| multiunit housing| apartment|secondhand smoke| thirdhand-smoke| united-states| us children| nicotine| association| asthma| home| adolescents| dust	Wilson, KM; Klein, JD; Blumkin, AK; Gottlieb, M; Winickoff, JP	Tobacco-Smoke Exposure in Children Who Live in Multiunit Housing		PEDIATRICS	secondhand smoke; passive smoking; environmental tobacco smoke; multiunit housing; apartment	SECONDHAND SMOKE; THIRDHAND-SMOKE; UNITED-STATES; US CHILDREN; NICOTINE; ASSOCIATION; ASTHMA; HOME; ADOLESCENTS; DUST	OBJECTIVE: There is no safe level of secondhand tobacco-smoke exposure, and no previous studies have explored multiunit housing as a potential contributor to secondhand tobacco-smoke exposure in children. We hypothesized that children who live in apartments have higher cotinine levels than those who live in detached homes, when controlling for demographics. METHODS: We analyzed data from the 2001-2006 National Health and Nutrition Examination Survey. The housing types we included in our study were detached houses (including mobile homes), attached houses, and apartments. Our study subjects were children between the ages of 6 and 18 years. Cotinine levels were used to assess secondhand tobacco-smoke exposure, and those living with someone who smoked inside the home were excluded. chi(2) tests, t tests, and Tobit regression models were used in Stata. Sample weights accounted for the complex survey design. RESULTS: Of 5002 children in our study, 73% were exposed to secondhand tobacco smoke. Children living in apartments had an increase in cotinine of 45% over those living in detached houses. This increase was 212% (P < .01) for white residents and 46% (P < .03) for black residents, but there was no significant increase for those of other races/ethnicities. At every cutoff level of cotinine, children in apartments had higher rates of exposure. The exposure effect of housing type was most pronounced at lower levels of cotinine. CONCLUSIONS: Most children without known secondhand tobacco-smoke exposure inside the home still showed evidence of tobacco-smoke exposure. Children in apartments had higher mean cotinine levels than children in detached houses. Potential causes for this result could be seepage through walls or shared ventilation systems. Smoking bans in multiunit housing may reduce children's exposure to tobacco smoke. Pediatrics 2011;127:85-92	39	72	2011	8	10.1542/peds.2010-2046	Pediatrics
Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-beta in bronchial epithelial cells from donors with asthma. Background Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that strongly activates dendritic cells and can initiate allergic inflammation. Since exposure to rhinovirus or double-stranded (ds) RNA (a surrogate of viral infection) induces TSLP expression in bronchial epithelial cells (BECs), this cytokine may link innate antiviral responses and the type 2 adaptive immune response. Objective As BECs from donors with asthma have a deficient interferon (IFN) response to rhinovirus infection, a study was undertaken to test the hypothesis that their antiviral response shows a bias towards TSLP production. Methods Primary BECs were grown from subjects with asthma and healthy volunteers. After exposure to dsRNA, interleukin (IL)-8, IFN beta and TSLP mRNA and protein expression were measured by RT-qPCR and ELISA, respectively. Results dsRNA dose-dependently increased IL-8 expression in BECs with no significant difference between the groups. However, BECs from subjects with asthma expressed less IFN beta and more TSLP mRNA and protein in response to dsRNA than BECs from those without asthma (median (IQR) 57 (38-82) pg/ml vs 106 (57-214) pg/ml for IFN beta (p<0.05) and 114 (86-143) pg/ml vs 65 (32-119) pg/ml for TSLP (p<0.05) in response to 10 mu g/ml dsRNA for 24 h). Induction of TSLP mRNA by dsRNA was blocked by Toll-like receptor 3 or protein kinase inhibitors or by preventing de novo protein synthesis, but not by neutralisation of type I IFN receptors. Conclusion BECs from subjects with asthma are biased towards higher TSLP and lower IFN beta production in response to dsRNA, suggesting that viral infection in asthma may lead to an altered mediator profile that biases towards a Th2 immune response.. mediated allergic inflammation| toll-like receptor-3| rhinovirus infection| viral-infections| protein-kinase| in-vitro| exacerbations| chemokines| disease| phenotype.	JUL-2010	mediated allergic inflammation| toll-like receptor-3| rhinovirus infection| viral-infections| protein-kinase| in-vitro| exacerbations| chemokines| disease| phenotype	Uller, L; Leino, M; Bedke, N; Sammut, D; Green, B; Lau, L; Howarth, PH; Holgate, ST; Davies, DE	Double-stranded RNA induces disproportionate expression of thymic stromal lymphopoietin versus interferon-beta in bronchial epithelial cells from donors with asthma		THORAX		MEDIATED ALLERGIC INFLAMMATION; TOLL-LIKE RECEPTOR-3; RHINOVIRUS INFECTION; VIRAL-INFECTIONS; PROTEIN-KINASE; IN-VITRO; EXACERBATIONS; CHEMOKINES; DISEASE; PHENOTYPE	Background Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that strongly activates dendritic cells and can initiate allergic inflammation. Since exposure to rhinovirus or double-stranded (ds) RNA (a surrogate of viral infection) induces TSLP expression in bronchial epithelial cells (BECs), this cytokine may link innate antiviral responses and the type 2 adaptive immune response. Objective As BECs from donors with asthma have a deficient interferon (IFN) response to rhinovirus infection, a study was undertaken to test the hypothesis that their antiviral response shows a bias towards TSLP production. Methods Primary BECs were grown from subjects with asthma and healthy volunteers. After exposure to dsRNA, interleukin (IL)-8, IFN beta and TSLP mRNA and protein expression were measured by RT-qPCR and ELISA, respectively. Results dsRNA dose-dependently increased IL-8 expression in BECs with no significant difference between the groups. However, BECs from subjects with asthma expressed less IFN beta and more TSLP mRNA and protein in response to dsRNA than BECs from those without asthma (median (IQR) 57 (38-82) pg/ml vs 106 (57-214) pg/ml for IFN beta (p<0.05) and 114 (86-143) pg/ml vs 65 (32-119) pg/ml for TSLP (p<0.05) in response to 10 mu g/ml dsRNA for 24 h). Induction of TSLP mRNA by dsRNA was blocked by Toll-like receptor 3 or protein kinase inhibitors or by preventing de novo protein synthesis, but not by neutralisation of type I IFN receptors. Conclusion BECs from subjects with asthma are biased towards higher TSLP and lower IFN beta production in response to dsRNA, suggesting that viral infection in asthma may lead to an altered mediator profile that biases towards a Th2 immune response.	35	72	2010	7	10.1136/thx.2009.125930	Respiratory System
"Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups. BACKGROUND: We recently reported that various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro. OBJECTIVES: We hypothesized that environmental estrogens Would enhance allergic sensitization as well as bronchial inflammation and responsiveness. To test this hypothesis, we exposed fetal and neonatal mice to the common environmental estrogen bisphenol A (BPA) via maternal loading and assessed the pups' response to allergic sensitization and bronchial challenge. METHODS: Female BALB/c mice received 10 mu g/mL BPA in their drinking water from I week before impregnation to the end of the study. Neonatal mice were given a single 5 mu g intraperitoneal dose of ovalbumin (OVA) with aluminum hydroxide on postnatal day 4 and 3% OVA by nebulization for 10 ruin on days 13, 14, and 15. Forty-eight hours after the last nebulization, we assessed serum IgE antibodies to OVA by enzyme-linked immunosorbent assay (ELISA) and airway inflammation and hyperresponsiveness by enumerating eosinophils in bronchoalveolar lavage fluid, whole-body barometric plethysmography, and a forced oscillation technique. RESULTS: Neonates from BPA-exposed mothers responded to this ""suboptimal"" sensitization with higher serum IgE anti-OVA concentrations compared with those from unexposed mothers (p < 0.05), and eosinophilic inflammation in their airways was significantly greater. Airway responsiveness of the OVA-sensitized neonates from BPA-treated mothers was enhanced compared with those from unexposed mothers (P < 0.05). CONCLUSIONS: Perinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a Susceptible animal model of asthma.. airway hyperresponsiveness| asthma| bisphenol a| environmental estrogen| eosinophilia| experimental asthma| ige| maternal exposure| perinatal sensitization|tandem mass-spectrometry| solid-phase extraction| t-cell responses| breast-milk| early-life| endocrine disruptors| immune-system| cord-blood| er-alpha| mice."	FEB-2010	airway hyperresponsiveness| asthma| bisphenol a| environmental estrogen| eosinophilia| experimental asthma| ige| maternal exposure| perinatal sensitization|tandem mass-spectrometry| solid-phase extraction| t-cell responses| breast-milk| early-life| endocrine disruptors| immune-system| cord-blood| er-alpha| mice	Midoro-Horiuti, T; Tiwari, R; Watson, CS; Goldblum, RM	Maternal Bisphenol A Exposure Promotes the Development of Experimental Asthma in Mouse Pups		ENVIRONMENTAL HEALTH PERSPECTIVES	airway hyperresponsiveness; asthma; bisphenol A; environmental estrogen; eosinophilia; experimental asthma; IgE; maternal exposure; perinatal sensitization	TANDEM MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; T-CELL RESPONSES; BREAST-MILK; EARLY-LIFE; ENDOCRINE DISRUPTORS; IMMUNE-SYSTEM; CORD-BLOOD; ER-ALPHA; MICE	"BACKGROUND: We recently reported that various environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators in vitro. OBJECTIVES: We hypothesized that environmental estrogens Would enhance allergic sensitization as well as bronchial inflammation and responsiveness. To test this hypothesis, we exposed fetal and neonatal mice to the common environmental estrogen bisphenol A (BPA) via maternal loading and assessed the pups' response to allergic sensitization and bronchial challenge. METHODS: Female BALB/c mice received 10 mu g/mL BPA in their drinking water from I week before impregnation to the end of the study. Neonatal mice were given a single 5 mu g intraperitoneal dose of ovalbumin (OVA) with aluminum hydroxide on postnatal day 4 and 3% OVA by nebulization for 10 ruin on days 13, 14, and 15. Forty-eight hours after the last nebulization, we assessed serum IgE antibodies to OVA by enzyme-linked immunosorbent assay (ELISA) and airway inflammation and hyperresponsiveness by enumerating eosinophils in bronchoalveolar lavage fluid, whole-body barometric plethysmography, and a forced oscillation technique. RESULTS: Neonates from BPA-exposed mothers responded to this ""suboptimal"" sensitization with higher serum IgE anti-OVA concentrations compared with those from unexposed mothers (p < 0.05), and eosinophilic inflammation in their airways was significantly greater. Airway responsiveness of the OVA-sensitized neonates from BPA-treated mothers was enhanced compared with those from unexposed mothers (P < 0.05). CONCLUSIONS: Perinatal exposure to BPA enhances allergic sensitization and bronchial inflammation and responsiveness in a Susceptible animal model of asthma."	44	72	2010	5	10.1289/ehp.0901259	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Influence of comorbid conditions on asthma. Various conditions such as rhinosinusitis, gastro-oesophageal reflux disease, psychological disturbances, chronic Infections and obstructive sleep apnoea are often observed In asthmatic patients and may affect asthma control and outcomes. These comorbidities may change the asthma phenotype, be part of the same pathophysiological process, act as confounding factors In the diagnosis or assessment of control of asthma, and/or result from specific environmental exposures. The Influences of these conditions on asthma are variable and for many of them still uncertain; nevertheless, they may alter asthma responses to current therapy. A systematic evaluation and an appropriate treatment of asthma-associated comorbid conditions should be part of asthma management, particularly for severe disease. With regard to clinical research, associated conditions may Influence the results of trials and should be taken Into account in the subjects' Inclusion criteria and analysis of data.. asthma comorbidities| gastro-oesophageal reflux disease| glottic dysfunction| obesity| obstructive sleep apnoea| rhinitis/sinusitis|quality-of-life| obstructive pulmonary-disease| allergic rhinitis| airway inflammation| sleep-apnea| follow-up| atopic-dermatitis| incident asthma| lung-function| gastroesophageal-reflux.	APR-2009	asthma comorbidities| gastro-oesophageal reflux disease| glottic dysfunction| obesity| obstructive sleep apnoea| rhinitis/sinusitis|quality-of-life| obstructive pulmonary-disease| allergic rhinitis| airway inflammation| sleep-apnea| follow-up| atopic-dermatitis| incident asthma| lung-function| gastroesophageal-reflux	Boulet, LP	Influence of comorbid conditions on asthma		EUROPEAN RESPIRATORY JOURNAL	Asthma comorbidities; gastro-oesophageal reflux disease; glottic dysfunction; obesity; obstructive sleep apnoea; rhinitis/sinusitis	QUALITY-OF-LIFE; OBSTRUCTIVE PULMONARY-DISEASE; ALLERGIC RHINITIS; AIRWAY INFLAMMATION; SLEEP-APNEA; FOLLOW-UP; ATOPIC-DERMATITIS; INCIDENT ASTHMA; LUNG-FUNCTION; GASTROESOPHAGEAL-REFLUX	Various conditions such as rhinosinusitis, gastro-oesophageal reflux disease, psychological disturbances, chronic Infections and obstructive sleep apnoea are often observed In asthmatic patients and may affect asthma control and outcomes. These comorbidities may change the asthma phenotype, be part of the same pathophysiological process, act as confounding factors In the diagnosis or assessment of control of asthma, and/or result from specific environmental exposures. The Influences of these conditions on asthma are variable and for many of them still uncertain; nevertheless, they may alter asthma responses to current therapy. A systematic evaluation and an appropriate treatment of asthma-associated comorbid conditions should be part of asthma management, particularly for severe disease. With regard to clinical research, associated conditions may Influence the results of trials and should be taken Into account in the subjects' Inclusion criteria and analysis of data.	121	72	2009	10	10.1183/09031936.00121308	Respiratory System
Asthma in Latin America: a public health challenge and research opportunity. Asthma has emerged as an important public health problem in many Latin American countries over the past decade. In Brazil and Costa Rica, the prevalence of asthma and associated morbidity is as great or greater as reported in traditional high prevalence countries such as the US, but remains neglected as a public health priority. Asthma in Latin America is associated particularly with underprivileged populations living in cities but remains relatively rare in many rural populations. The causes of asthma in Latin America are likely to be associated with urbanization, migration, and the adoption of a modern 'Westernized' lifestyle and environmental changes that follow these processes that include changes in diet, physical activity, hygiene, and exposures to allergens, irritants, and outdoor and indoor pollutants. Because of the enormous social, genetic, and environmental contrasts within and between Latin American countries, and the large differences in prevalence associated with these differences, the investigation of asthma in Latin America provides important research opportunities to identify the social and biological mechanisms that underlie asthma development. Asthma in Latin America poses enormous challenges for health policy makers, health services, and researchers to respond to and alleviate the growing burden of asthma disability, particularly among marginalized urban populations.. asthma| allergy| latin america| urbanization|schistosoma-mansoni infection| body-mass index| childhood asthma| risk-factors| school-children| allergic sensitization| ascaris-lumbricoides| costa-rica| rural area| bronchial responsiveness.	JAN-2009	asthma| allergy| latin america| urbanization|schistosoma-mansoni infection| body-mass index| childhood asthma| risk-factors| school-children| allergic sensitization| ascaris-lumbricoides| costa-rica| rural area| bronchial responsiveness	Cooper, PJ; Rodrigues, LC; Cruz, AA; Barreto, ML	Asthma in Latin America: a public health challenge and research opportunity		ALLERGY	asthma; allergy; Latin America; urbanization	SCHISTOSOMA-MANSONI INFECTION; BODY-MASS INDEX; CHILDHOOD ASTHMA; RISK-FACTORS; SCHOOL-CHILDREN; ALLERGIC SENSITIZATION; ASCARIS-LUMBRICOIDES; COSTA-RICA; RURAL AREA; BRONCHIAL RESPONSIVENESS	Asthma has emerged as an important public health problem in many Latin American countries over the past decade. In Brazil and Costa Rica, the prevalence of asthma and associated morbidity is as great or greater as reported in traditional high prevalence countries such as the US, but remains neglected as a public health priority. Asthma in Latin America is associated particularly with underprivileged populations living in cities but remains relatively rare in many rural populations. The causes of asthma in Latin America are likely to be associated with urbanization, migration, and the adoption of a modern 'Westernized' lifestyle and environmental changes that follow these processes that include changes in diet, physical activity, hygiene, and exposures to allergens, irritants, and outdoor and indoor pollutants. Because of the enormous social, genetic, and environmental contrasts within and between Latin American countries, and the large differences in prevalence associated with these differences, the investigation of asthma in Latin America provides important research opportunities to identify the social and biological mechanisms that underlie asthma development. Asthma in Latin America poses enormous challenges for health policy makers, health services, and researchers to respond to and alleviate the growing burden of asthma disability, particularly among marginalized urban populations.	114	72	2009	13	10.1111/j.1398-9995.2008.01902.x	Allergy; Immunology
Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone-induced pulmonary inflammation. We previously reported that genetically obese mice exhibit innate airway hyperresponsiveness (AHR) and enhanced ozone (O-3)-induced pulmonary inflammation. Such genetic deficiencies in mice are rare in humans, and they may not be representative of human obesity. Thus the purpose of this study was to determine the pulmonary phenotype of mice with diet-induced obesity (DIO), which more closely mimics the cause of human obesity. Therefore, wild-type C57BL/6 mice were reared from the time of weaning until at least 30 wk of age on diets in which either 10 or 60% of the calories are derived from fat in the form of lard. Body mass was similar to 40% greater in mice fed 60 vs. 10% fat diets. Baseline airway responsiveness to intravenous methacholine, measured by forced oscillation, was greater in mice fed 60 vs. 10% fat diets. We also examined lung permeability and inflammation after exposure to room air or O-3 (2 parts/million for 3 h), an asthma trigger. Four hours after the exposure ended, O-3-induced increases in bronchoalveolar lavage fluid protein, interleukin-6, KC, macrophage inflammatory protein-2, interferon-gamma-inducible protein-10, and eotaxin were greater in mice fed 60 vs. 10% fat diets. Innate AHR and augmented responses to O-3 were not observed in mice raised from weaning until 20-22 wk of age on a 60% fat diet. These results indicate that mice with DIO exhibit innate AHR and enhanced O3-induced pulmonary inflammation, similar to genetically obese mice. However, mice with DIO must remain obese for an extended period of time before this pulmonary phenotype is observed.. bronchoalveolar lavage fluid| chemokine| leptin| lung elastance| resistance|high-fat diet| necrosis-factor-alpha| induced lung inflammation| body-mass index| insulin-resistance| tissue mechanics| deficient mice| c57bl/6j mice| asthma| responses.	JUN-2008	bronchoalveolar lavage fluid| chemokine| leptin| lung elastance| resistance|high-fat diet| necrosis-factor-alpha| induced lung inflammation| body-mass index| insulin-resistance| tissue mechanics| deficient mice| c57bl/6j mice| asthma| responses	Johnston, RA; Theman, TA; Lu, FL; Terry, RD; Williams, ES; Shore, SA	Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone-induced pulmonary inflammation		JOURNAL OF APPLIED PHYSIOLOGY	bronchoalveolar lavage fluid; chemokine; leptin; lung elastance; resistance	HIGH-FAT DIET; NECROSIS-FACTOR-ALPHA; INDUCED LUNG INFLAMMATION; BODY-MASS INDEX; INSULIN-RESISTANCE; TISSUE MECHANICS; DEFICIENT MICE; C57BL/6J MICE; ASTHMA; RESPONSES	We previously reported that genetically obese mice exhibit innate airway hyperresponsiveness (AHR) and enhanced ozone (O-3)-induced pulmonary inflammation. Such genetic deficiencies in mice are rare in humans, and they may not be representative of human obesity. Thus the purpose of this study was to determine the pulmonary phenotype of mice with diet-induced obesity (DIO), which more closely mimics the cause of human obesity. Therefore, wild-type C57BL/6 mice were reared from the time of weaning until at least 30 wk of age on diets in which either 10 or 60% of the calories are derived from fat in the form of lard. Body mass was similar to 40% greater in mice fed 60 vs. 10% fat diets. Baseline airway responsiveness to intravenous methacholine, measured by forced oscillation, was greater in mice fed 60 vs. 10% fat diets. We also examined lung permeability and inflammation after exposure to room air or O-3 (2 parts/million for 3 h), an asthma trigger. Four hours after the exposure ended, O-3-induced increases in bronchoalveolar lavage fluid protein, interleukin-6, KC, macrophage inflammatory protein-2, interferon-gamma-inducible protein-10, and eotaxin were greater in mice fed 60 vs. 10% fat diets. Innate AHR and augmented responses to O-3 were not observed in mice raised from weaning until 20-22 wk of age on a 60% fat diet. These results indicate that mice with DIO exhibit innate AHR and enhanced O3-induced pulmonary inflammation, similar to genetically obese mice. However, mice with DIO must remain obese for an extended period of time before this pulmonary phenotype is observed.	72	72	2008	9	10.1152/japplphysiol.00075.2008	Physiology; Sport Sciences
The prevalence of atopic triad in children with physician-confirmed atopic dermatitis. Background: Atopic dermatitis (AD) is often associated with comorbidities such as allergic rhinitis and asthma. Objective: We sought to describe the frequency of these comorbidities in children with AD Methods: We conducted a cross-sectional study of the first 2270 children with physician-confirmed AD enrolled in a large postmarketing cohort. All were queried for information on comorbidities using a questionnaire from the International Study of Asthma and Allergies in Childhood. Results: In all, 71.3% reported at least one additional form of atopy (symptoms of asthma or allergic rhinitis). A total of 33.3% reported only symptoms of asthma or allergic rhinitis whereas 38.0% reported I symptoms of asthma and allergic rhinitis. By age 3 years, nearly 66% reported at least one additional form of atopy. A statistically significant trend toward poorer disease control was observed for those with additional atopic illnesses (P <.001). Limitations: This is a cross-sectional study Conclusion: Individuals with AD exhibit a predisposition to additional atopic illnesses by age 3 years and in turn the presence of these illnesses correlates with poor disease control.. follow-up| asthma| childhood| predispose| mutations| allergies| exposure| criteria| eczema| isaac.	JAN-2008	follow-up| asthma| childhood| predispose| mutations| allergies| exposure| criteria| eczema| isaac	Kapoor, R; Menon, C; Hoffstad, O; Bilker, W; Leclerc, P; Margolis, DJ	The prevalence of atopic triad in children with physician-confirmed atopic dermatitis		JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY		FOLLOW-UP; ASTHMA; CHILDHOOD; PREDISPOSE; MUTATIONS; ALLERGIES; EXPOSURE; CRITERIA; ECZEMA; ISAAC	Background: Atopic dermatitis (AD) is often associated with comorbidities such as allergic rhinitis and asthma. Objective: We sought to describe the frequency of these comorbidities in children with AD Methods: We conducted a cross-sectional study of the first 2270 children with physician-confirmed AD enrolled in a large postmarketing cohort. All were queried for information on comorbidities using a questionnaire from the International Study of Asthma and Allergies in Childhood. Results: In all, 71.3% reported at least one additional form of atopy (symptoms of asthma or allergic rhinitis). A total of 33.3% reported only symptoms of asthma or allergic rhinitis whereas 38.0% reported I symptoms of asthma and allergic rhinitis. By age 3 years, nearly 66% reported at least one additional form of atopy. A statistically significant trend toward poorer disease control was observed for those with additional atopic illnesses (P <.001). Limitations: This is a cross-sectional study Conclusion: Individuals with AD exhibit a predisposition to additional atopic illnesses by age 3 years and in turn the presence of these illnesses correlates with poor disease control.	29	72	2008	6	10.1016/j.jaad.2007.06.041	Dermatology
Occupational health problems in modern dentistry: A review. Despite numerous technical advances in recent years, many occupational health problems still persist in modern dentistry. These include percutaneous exposure incidents (PEI); exposure to infectious diseases (including bioaerosols), radiation, dental materials, and noise; musculoskeletal disorders; dermatitis and respiratory disorders; eye injuries; and psychological problems. PEI remain a particular concern, as there is an almost constant risk of exposure to serious infectious agents. Strategies to minimise PEI and their consequences should continue to be employed, including sound infection control practices, continuing education and hepatitis B immunisation. As part of any infection control protocols, dentists should continue to utilise personal protective measures and appropriate sterilisation or other high-level disinfection techniques. Aside from biological hazards, dentists continue to suffer a high prevalence of musculoskeletal disorders (MSD), especially of the back, neck and shoulders. To fully understand the nature of these problems, further studies are needed to identify causative factors and other correlates of MSD. Continuing education and investigation of appropriate interventions to help reduce the prevalence of MSD and contact dermatitis are also needed. For these reasons, it is therefore important that dentists remain constantly informed regarding up-to-date measures on how to deal with newer technologies and dental materials.. dentistry| infectious diseases| dermatitis| musculoskeletal pain|general dental practitioners| musculoskeletal disorders| southern thailand| bacterial aerosols| hand dermatitis| latex| personnel| prevalence| allergy| infection.	OCT-2007	dentistry| infectious diseases| dermatitis| musculoskeletal pain|general dental practitioners| musculoskeletal disorders| southern thailand| bacterial aerosols| hand dermatitis| latex| personnel| prevalence| allergy| infection	Leggat, PA; Kedjarune, U; Smith, DR	Occupational health problems in modern dentistry: A review		INDUSTRIAL HEALTH	dentistry; infectious diseases; dermatitis; musculoskeletal pain	GENERAL DENTAL PRACTITIONERS; MUSCULOSKELETAL DISORDERS; SOUTHERN THAILAND; BACTERIAL AEROSOLS; HAND DERMATITIS; LATEX; PERSONNEL; PREVALENCE; ALLERGY; INFECTION	Despite numerous technical advances in recent years, many occupational health problems still persist in modern dentistry. These include percutaneous exposure incidents (PEI); exposure to infectious diseases (including bioaerosols), radiation, dental materials, and noise; musculoskeletal disorders; dermatitis and respiratory disorders; eye injuries; and psychological problems. PEI remain a particular concern, as there is an almost constant risk of exposure to serious infectious agents. Strategies to minimise PEI and their consequences should continue to be employed, including sound infection control practices, continuing education and hepatitis B immunisation. As part of any infection control protocols, dentists should continue to utilise personal protective measures and appropriate sterilisation or other high-level disinfection techniques. Aside from biological hazards, dentists continue to suffer a high prevalence of musculoskeletal disorders (MSD), especially of the back, neck and shoulders. To fully understand the nature of these problems, further studies are needed to identify causative factors and other correlates of MSD. Continuing education and investigation of appropriate interventions to help reduce the prevalence of MSD and contact dermatitis are also needed. For these reasons, it is therefore important that dentists remain constantly informed regarding up-to-date measures on how to deal with newer technologies and dental materials.	100	72	2007	11	10.2486/indhealth.45.611	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization. Fragrances are common causes of contact allergy. Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an important fragrance terpene. It is considered a weak contact allergen and is used for fragrance allergy screening among consecutive dermatitis patients. Analogous to other monoterpenes studied, such as limonene and linalool, geraniol has the potential to autoxidize on air exposure and form highly allergenic compounds. The aim of the present study was to investigate and propose a mechanism for the autoxidation of geraniol at room temperature. To investigate whether allergenic compounds are formed, the sensitizing potency of geraniol itself, air-exposed geraniol, and its oxidation products was determined using the local lymph node assay in mice. The results obtained show that the allylic alcohol geraniol follows an oxidation pattern different from those of linalool and limonene, which autoxidize forming hydroperoxides as the only primary oxidation products. The autoxidation of geraniol follows two paths, originating from allylic hydrogen abstraction near the two double bonds. From geraniol, hydrogen peroxide is primarily formed together with aldehydes geranial and neral from a hydroxyhydroperoxide. In addition, small amounts of a hydroperoxide are formed, analogous to the formation of the major linalool hydroperoxide. The autoxidation of geraniol greatly influenced the sensitizing effect of geraniol. The oxidized samples had moderate sensitizing capacity, quite different from that of pure geraniol. The hydroperoxide formed is believed to be the major contributor to allergenic activity, together with the aldehydes geranial and neral. On the basis of the present study and previous experience, we recommend that the possibility of autoxidation and the subsequent formation of contact allergenic oxidation products are considered in risk assessments performed on fragrance terpenes.. oxidized d-limonene| lymph-node assay| dermatitis| hydroperoxides| aldehydes| capacity| linalool| potency| common.	MAY-2007	oxidized d-limonene| lymph-node assay| dermatitis| hydroperoxides| aldehydes| capacity| linalool| potency| common	Hagvall, L; Backtorp, C; Svensson, S; Nyman, G; Borje, A; Karlberg, AT	Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization		CHEMICAL RESEARCH IN TOXICOLOGY		OXIDIZED D-LIMONENE; LYMPH-NODE ASSAY; DERMATITIS; HYDROPEROXIDES; ALDEHYDES; CAPACITY; LINALOOL; POTENCY; COMMON	Fragrances are common causes of contact allergy. Geraniol (trans-3,7-dimethyl-2,6-octadiene-1-ol) is an important fragrance terpene. It is considered a weak contact allergen and is used for fragrance allergy screening among consecutive dermatitis patients. Analogous to other monoterpenes studied, such as limonene and linalool, geraniol has the potential to autoxidize on air exposure and form highly allergenic compounds. The aim of the present study was to investigate and propose a mechanism for the autoxidation of geraniol at room temperature. To investigate whether allergenic compounds are formed, the sensitizing potency of geraniol itself, air-exposed geraniol, and its oxidation products was determined using the local lymph node assay in mice. The results obtained show that the allylic alcohol geraniol follows an oxidation pattern different from those of linalool and limonene, which autoxidize forming hydroperoxides as the only primary oxidation products. The autoxidation of geraniol follows two paths, originating from allylic hydrogen abstraction near the two double bonds. From geraniol, hydrogen peroxide is primarily formed together with aldehydes geranial and neral from a hydroxyhydroperoxide. In addition, small amounts of a hydroperoxide are formed, analogous to the formation of the major linalool hydroperoxide. The autoxidation of geraniol greatly influenced the sensitizing effect of geraniol. The oxidized samples had moderate sensitizing capacity, quite different from that of pure geraniol. The hydroperoxide formed is believed to be the major contributor to allergenic activity, together with the aldehydes geranial and neral. On the basis of the present study and previous experience, we recommend that the possibility of autoxidation and the subsequent formation of contact allergenic oxidation products are considered in risk assessments performed on fragrance terpenes.	40	72	2007	8	10.1021/tx700017v	Pharmacology & Pharmacy; Chemistry; Toxicology
Thunderstorm-asthma and pollen allergy. Thunderstorms have been linked to asthma epidemics, especially during the pollen seasons, and there are descriptions of asthma outbreaks associated with thunderstorms, which occurred in several cities, prevalently in Europe (Birmingham and London in the UK and Napoli in Italy) and Australia (Melbourne and Wagga Wagga). Pollen grains can be carried by thunderstorm at ground level, where pollen rupture would be increased with release of allergenic biological aerosols of paucimicronic size, derived from the cytoplasm and which can penetrate deep into lower airways. In other words, there is evidence that under wet conditions or during thunderstorms, pollen grains may, after rupture by osmotic shock, release into the atmosphere part of their content, including respirable, allergen-carrying cytoplasmic starch granules (0.5-2.5 mu m) or other paucimicronic components that can reach lower airways inducing asthma reactions in pollinosis patients. The thunderstorm-asthma outbreaks are characterized, at the beginning of thunderstorms by a rapid increase of visits for asthma in general practitioner or hospital emergency departments. Subjects without asthma symptoms, but affected by seasonal rhinitis can experience an asthma attack. No unusual levels of air pollution were noted at the time of the epidemics, but there was a strong association with high atmospheric concentrations of pollen grains such as grasses or other allergenic plant species. However, subjects affected by pollen allergy should be informed about a possible risk of asthma attack at the beginning of a thunderstorm during pollen season.. allergic asthma| bronchial asthma| bronchial hyperreactivity| climate changes| environment and allergy| pollen allergy| pollinosis| respiratory allergy| thunderstorm-asthma|grass-pollen| environmental-factors| air-pollution| hay-fever| epidemics| risk| sensitization| community| orbicules| outbreak.	JAN-2007	allergic asthma| bronchial asthma| bronchial hyperreactivity| climate changes| environment and allergy| pollen allergy| pollinosis| respiratory allergy| thunderstorm-asthma|grass-pollen| environmental-factors| air-pollution| hay-fever| epidemics| risk| sensitization| community| orbicules| outbreak	D'Amato, G; Liccardi, G; Frenguelli, G	Thunderstorm-asthma and pollen allergy		ALLERGY	allergic asthma; bronchial asthma; bronchial hyperreactivity; climate changes; environment and allergy; pollen allergy; pollinosis; respiratory allergy; thunderstorm-asthma	GRASS-POLLEN; ENVIRONMENTAL-FACTORS; AIR-POLLUTION; HAY-FEVER; EPIDEMICS; RISK; SENSITIZATION; COMMUNITY; ORBICULES; OUTBREAK	Thunderstorms have been linked to asthma epidemics, especially during the pollen seasons, and there are descriptions of asthma outbreaks associated with thunderstorms, which occurred in several cities, prevalently in Europe (Birmingham and London in the UK and Napoli in Italy) and Australia (Melbourne and Wagga Wagga). Pollen grains can be carried by thunderstorm at ground level, where pollen rupture would be increased with release of allergenic biological aerosols of paucimicronic size, derived from the cytoplasm and which can penetrate deep into lower airways. In other words, there is evidence that under wet conditions or during thunderstorms, pollen grains may, after rupture by osmotic shock, release into the atmosphere part of their content, including respirable, allergen-carrying cytoplasmic starch granules (0.5-2.5 mu m) or other paucimicronic components that can reach lower airways inducing asthma reactions in pollinosis patients. The thunderstorm-asthma outbreaks are characterized, at the beginning of thunderstorms by a rapid increase of visits for asthma in general practitioner or hospital emergency departments. Subjects without asthma symptoms, but affected by seasonal rhinitis can experience an asthma attack. No unusual levels of air pollution were noted at the time of the epidemics, but there was a strong association with high atmospheric concentrations of pollen grains such as grasses or other allergenic plant species. However, subjects affected by pollen allergy should be informed about a possible risk of asthma attack at the beginning of a thunderstorm during pollen season.	35	72	2007	6	10.1111/j.1398-9995.2006.01271.x	Allergy; Immunology
Crucial commitment of proteolytic activity of a purified recombinant major house dust mite allergen der p1 to sensitization toward IgE and IgG responses. The major proteolytic allergen derived from the house dust mite Dermatophagoides pteronyssinus, Der Ill, is one of the most clinically relevant allergens worldwide. In the present study, we evaluate the contribution of the proteolytic activity and structure of a highly purified rDer p 1 to immune responses. Mice were i.p. immunized with three forms of rDer p I adsorbed to Alum: one enzymatically active, one treated with an irreversible cysteine protease-specific inhibitor, E-64, and one heat denatured. Immunization with E-64-treated or heat-denatured rDer p I elicited much less production of serum total IgE and not only rDer p 1-specific IgE but also IgGs compared with immunization with active rDer p 1. Assays for Ab-binding and its inhibition and structural analyses indicated that E-64-treated rDer p I retained its global structure and conformational B cell epitopes. A proliferative response and production of IL-5 by spleen cells restimulated with rDer p I were observed on immunization with the active rDer p 1 but not E-64-treated rDer p 1. The cells from mice immunized with heat-denatured rDer p I exhibited the highest levels of proliferation and production of IL-5 and IFN-gamma. The results indicate that the proteolytic activity of the highly purified rDer p I crucially commits to the sensitization process, including both IgE and IgG responses. Additionally, we demonstrated immunogenic differences by functional or structural manipulations of the rDer p 1. The findings have implications for sensitization to this relevant allergen in humans and for the design of modified allergen-vaccines for future allergen-specific immunotherapy.. cysteine protease activity| der-f-i| dermatophagoides-pteronyssinus| crystal-structure| sequence polymorphisms| enhances allergenicity| potential allergens| antibody-response| heat denaturation| group-1 allergen.	AUG 1-2006	cysteine protease activity| der-f-i| dermatophagoides-pteronyssinus| crystal-structure| sequence polymorphisms| enhances allergenicity| potential allergens| antibody-response| heat denaturation| group-1 allergen	Kikuchi, Y; Takai, T; Kuhara, T; Ota, M; Kato, T; Hatanaka, H; Ichikawa, S; Tokura, T; Akiba, H; Mitsuishi, K; Ikeda, S; Okumura, K; Ogawa, H	Crucial commitment of proteolytic activity of a purified recombinant major house dust mite allergen der p1 to sensitization toward IgE and IgG responses		JOURNAL OF IMMUNOLOGY		CYSTEINE PROTEASE ACTIVITY; DER-F-I; DERMATOPHAGOIDES-PTERONYSSINUS; CRYSTAL-STRUCTURE; SEQUENCE POLYMORPHISMS; ENHANCES ALLERGENICITY; POTENTIAL ALLERGENS; ANTIBODY-RESPONSE; HEAT DENATURATION; GROUP-1 ALLERGEN	The major proteolytic allergen derived from the house dust mite Dermatophagoides pteronyssinus, Der Ill, is one of the most clinically relevant allergens worldwide. In the present study, we evaluate the contribution of the proteolytic activity and structure of a highly purified rDer p 1 to immune responses. Mice were i.p. immunized with three forms of rDer p I adsorbed to Alum: one enzymatically active, one treated with an irreversible cysteine protease-specific inhibitor, E-64, and one heat denatured. Immunization with E-64-treated or heat-denatured rDer p I elicited much less production of serum total IgE and not only rDer p 1-specific IgE but also IgGs compared with immunization with active rDer p 1. Assays for Ab-binding and its inhibition and structural analyses indicated that E-64-treated rDer p I retained its global structure and conformational B cell epitopes. A proliferative response and production of IL-5 by spleen cells restimulated with rDer p I were observed on immunization with the active rDer p 1 but not E-64-treated rDer p 1. The cells from mice immunized with heat-denatured rDer p I exhibited the highest levels of proliferation and production of IL-5 and IFN-gamma. The results indicate that the proteolytic activity of the highly purified rDer p I crucially commits to the sensitization process, including both IgE and IgG responses. Additionally, we demonstrated immunogenic differences by functional or structural manipulations of the rDer p 1. The findings have implications for sensitization to this relevant allergen in humans and for the design of modified allergen-vaccines for future allergen-specific immunotherapy.	73	72	2006	9		Immunology
A randomized controlled trial on office spirometry in asthma and COPD in standard general practice - Data from spirometry in asthma and COPD: a comparative evaluation Italian study. Study objectives: To evaluate whether office spirometry by general practitioners (GPs) is feasible and may improve the diagnosis of asthma and COPD. Methods: A prospective, randomized, comparative trial was planned involving 57 Italian pulmonology centers and 570 GPs who had to enroll consecutive subjects aged IS to 65 years with symptoms of asthma or COPD without a previous diagnosis. Patients were randomized 1:1 into two groups with an interactive voice responding system: conventional evaluation alone vs conventional evaluation and spirometry. Office spirometry was performed by GPs who were trained by reference specialists using a portable electronic spirometer (Spirobank Office; MIR; Home, Italy). Diagnosis was confirmed by the reference specialist center in blind fashion. Results: Seventy-four GPs complied to the trial. Of :333 patients enrolled, 136 nonrandom violators completed the protocol. Per-protocol analysis showed a concordant diagnosis between GPs and specialists in 78.6% of cases in the conventional evaluation-plus-spirometry group vs 69.2% in the conventional evaluation group (p = 0.35). In the intention-to-treat analysis, the respective percentages of concordant diagnosis were 57.9 and 56.7 (p = 0.87). Conclusions: Office spirometry by GPs is feasible, but frequent protocol violation and inadequate sample size did not allow us to prove a significant advantage of office spirometry in improving the diagnosis of asthma and COPD in standard general practice as organized at present in Italy, thus reinforcing the need for close cooperation between GPs and specialists in respiratory medicine.. asthma| copd| general practice| office spirometry|obstructive pulmonary-disease| primary-care| persistent cough| population| program.	APR-2006	asthma| copd| general practice| office spirometry|obstructive pulmonary-disease| primary-care| persistent cough| population| program	Lusuardi, M; De Benedetto, F; Paggiaro, P; Sanguinetti, CM; Brazzola, G; Ferri, P; Donner, CF	A randomized controlled trial on office spirometry in asthma and COPD in standard general practice - Data from spirometry in asthma and COPD: a comparative evaluation Italian study		CHEST	asthma; COPD; general practice; office spirometry	OBSTRUCTIVE PULMONARY-DISEASE; PRIMARY-CARE; PERSISTENT COUGH; POPULATION; PROGRAM	Study objectives: To evaluate whether office spirometry by general practitioners (GPs) is feasible and may improve the diagnosis of asthma and COPD. Methods: A prospective, randomized, comparative trial was planned involving 57 Italian pulmonology centers and 570 GPs who had to enroll consecutive subjects aged IS to 65 years with symptoms of asthma or COPD without a previous diagnosis. Patients were randomized 1:1 into two groups with an interactive voice responding system: conventional evaluation alone vs conventional evaluation and spirometry. Office spirometry was performed by GPs who were trained by reference specialists using a portable electronic spirometer (Spirobank Office; MIR; Home, Italy). Diagnosis was confirmed by the reference specialist center in blind fashion. Results: Seventy-four GPs complied to the trial. Of :333 patients enrolled, 136 nonrandom violators completed the protocol. Per-protocol analysis showed a concordant diagnosis between GPs and specialists in 78.6% of cases in the conventional evaluation-plus-spirometry group vs 69.2% in the conventional evaluation group (p = 0.35). In the intention-to-treat analysis, the respective percentages of concordant diagnosis were 57.9 and 56.7 (p = 0.87). Conclusions: Office spirometry by GPs is feasible, but frequent protocol violation and inadequate sample size did not allow us to prove a significant advantage of office spirometry in improving the diagnosis of asthma and COPD in standard general practice as organized at present in Italy, thus reinforcing the need for close cooperation between GPs and specialists in respiratory medicine.	19	72	2006	9	10.1378/chest.129.4.844	General & Internal Medicine; Respiratory System
Wheezing, asthma, hayfever, and atopic eczema in childhood following exposure to tobacco smoke in fetal life. Prenatal maternal smoking has been associated with adverse respiratory effects in childhood such as lung deficits and wheezing, but results concerning asthma, hayfever, and atopic eczema are inconsistent. In the present study, we investigate the effects of maternal smoking in pregnancy on asthma, hayfever, atopic eczema, and wheezing in the offspring up to the age of 14-18. The study was based on a cohort of mothers enrolled during midwife visits around the 36th week of gestation in Odense and Aalborg, Denmark, 1984-1987. Singleton, live born children (n=11 144) were followed-up in 2002 to obtain a childhood history of atopic diseases, by means of questionnaires to the parents. Multivariate logistic regression analyses for medical diagnoses of asthma, hayfever, atopic eczema, and symptoms of wheezing before the age of 3, were carried out on 7844 children. After adjustment for confounders, late prenatal smoke exposure was associated with wheezing, with an odds ratio (OR) of 1.2, and a 95% confidence interval (CI) of 1.1-1.5. Furthermore, slightly reduced estimates for hayfever (OR 0.8, CI 0.7-1.0) and atopic eczema (OR 0.8, CI 0.7-0.9) were obtained for children exposed in late pregnancy compared with non-exposed. Late gestational smoke exposure was associated with wheezing but not with asthma, while null or even protective estimates were indicated for hayfever and atopic eczema. However, lack of control options for hereditary factors may have affected the results.. atopic diseases| prenatal| smoke exposure| tobacco| wheezing|cord-serum ige| perinatal risk-factors| maternal smoking| parental smoking| lung-function| allergic sensitization| bronchial hyperresponsiveness| reproductive health| respiratory illness| family-history.	DEC-2005	atopic diseases| prenatal| smoke exposure| tobacco| wheezing|cord-serum ige| perinatal risk-factors| maternal smoking| parental smoking| lung-function| allergic sensitization| bronchial hyperresponsiveness| reproductive health| respiratory illness| family-history	Magnusson, LL; Olesen, AB; Wennborg, H; Olsen, J	Wheezing, asthma, hayfever, and atopic eczema in childhood following exposure to tobacco smoke in fetal life		CLINICAL AND EXPERIMENTAL ALLERGY	atopic diseases; prenatal; smoke exposure; tobacco; wheezing	CORD-SERUM IGE; PERINATAL RISK-FACTORS; MATERNAL SMOKING; PARENTAL SMOKING; LUNG-FUNCTION; ALLERGIC SENSITIZATION; BRONCHIAL HYPERRESPONSIVENESS; REPRODUCTIVE HEALTH; RESPIRATORY ILLNESS; FAMILY-HISTORY	Prenatal maternal smoking has been associated with adverse respiratory effects in childhood such as lung deficits and wheezing, but results concerning asthma, hayfever, and atopic eczema are inconsistent. In the present study, we investigate the effects of maternal smoking in pregnancy on asthma, hayfever, atopic eczema, and wheezing in the offspring up to the age of 14-18. The study was based on a cohort of mothers enrolled during midwife visits around the 36th week of gestation in Odense and Aalborg, Denmark, 1984-1987. Singleton, live born children (n=11 144) were followed-up in 2002 to obtain a childhood history of atopic diseases, by means of questionnaires to the parents. Multivariate logistic regression analyses for medical diagnoses of asthma, hayfever, atopic eczema, and symptoms of wheezing before the age of 3, were carried out on 7844 children. After adjustment for confounders, late prenatal smoke exposure was associated with wheezing, with an odds ratio (OR) of 1.2, and a 95% confidence interval (CI) of 1.1-1.5. Furthermore, slightly reduced estimates for hayfever (OR 0.8, CI 0.7-1.0) and atopic eczema (OR 0.8, CI 0.7-0.9) were obtained for children exposed in late pregnancy compared with non-exposed. Late gestational smoke exposure was associated with wheezing but not with asthma, while null or even protective estimates were indicated for hayfever and atopic eczema. However, lack of control options for hereditary factors may have affected the results.	66	72	2005	7		Allergy; Immunology
Interleukin-25 and interieukin-13 production by alveolar macrophages in response to particles. Particle inhalation-induced lung inflammation acts as an adjuvant to allergens or respiratory viral infection in a process that is mediated by macrophages and epitheliums. The production of interleukin (IL)-4 and IL-13 by activated T cells is involved in the augmentation of Th2-type immune responses to particles, and IL-25 induces the synthesis of 11-4 and IL-13. However, whether IL-13 and IL-25 are directly regulated by particle instillation in the lung has not been studied. The aim of this study was to reveal particle induction of IL-13 and IL-25 in the lung. TiO2 instillation potently induced the mRNA expression for IL-25 and IL-13 in lung tissue extracts 24 h after treatment, as compared with the sham group. Immunostaining for IL-25 and IL-13 showed strong positivity for macrophages in the inflammatory lung lesions of TiO2-treated rats. The alveolar macrophages expressed IL-25 and IL-13 24h after in vitro stimulation with TiO2 particles in dose- and time-dependent manners, with maximal induction at 24 and 48 h after stimulation, respectively. The sequence of the rat IL-25 gene is 95% homologous with the mouse IL-25 gene. These findings indicate that alveolar macrophages play an important role in particle-induced lung inflammation via direct induction of IL-13 and IL-25 production.. cytokines| inflammation| lung| macrophages|particulate air-pollution| in-vivo| diesel exhaust| chemokine expression| cytokine production| pulmonary-function| titanium-dioxide| cell-function| rat lung| matter.	SEP-2005	cytokines| inflammation| lung| macrophages|particulate air-pollution| in-vivo| diesel exhaust| chemokine expression| cytokine production| pulmonary-function| titanium-dioxide| cell-function| rat lung| matter	Kang, CM; Jang, AS; Ahn, MH; Shin, LA; Kim, JH; Choi, YS; Rhim, TY; Park, CS	Interleukin-25 and interieukin-13 production by alveolar macrophages in response to particles		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	cytokines; inflammation; lung; macrophages	PARTICULATE AIR-POLLUTION; IN-VIVO; DIESEL EXHAUST; CHEMOKINE EXPRESSION; CYTOKINE PRODUCTION; PULMONARY-FUNCTION; TITANIUM-DIOXIDE; CELL-FUNCTION; RAT LUNG; MATTER	Particle inhalation-induced lung inflammation acts as an adjuvant to allergens or respiratory viral infection in a process that is mediated by macrophages and epitheliums. The production of interleukin (IL)-4 and IL-13 by activated T cells is involved in the augmentation of Th2-type immune responses to particles, and IL-25 induces the synthesis of 11-4 and IL-13. However, whether IL-13 and IL-25 are directly regulated by particle instillation in the lung has not been studied. The aim of this study was to reveal particle induction of IL-13 and IL-25 in the lung. TiO2 instillation potently induced the mRNA expression for IL-25 and IL-13 in lung tissue extracts 24 h after treatment, as compared with the sham group. Immunostaining for IL-25 and IL-13 showed strong positivity for macrophages in the inflammatory lung lesions of TiO2-treated rats. The alveolar macrophages expressed IL-25 and IL-13 24h after in vitro stimulation with TiO2 particles in dose- and time-dependent manners, with maximal induction at 24 and 48 h after stimulation, respectively. The sequence of the rat IL-25 gene is 95% homologous with the mouse IL-25 gene. These findings indicate that alveolar macrophages play an important role in particle-induced lung inflammation via direct induction of IL-13 and IL-25 production.	44	72	2005	7	10.1165/rcmb.2005-0003OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Intestinal microbiota and immunoglobulin E responses in 5-year-old Estonian children. Background Over the last few decades, several studies from different parts of the world have indicated an increasing prevalence of allergic diseases. This has been related to environmental factors, like changes of microbial pressure. Our previous studies have demonstrated differences in the intestinal microbiota between allergic and non-allergic children. Aim To test the hypothesis that the intestinal microbiota and IgE response are related, both in allergic and non-allergic 5-year-old Estonian children. Methods The study group comprised 19 allergic and 19 non-allergic 5-year-old children, selected from a larger group who had been followed from birth. The diagnosis of allergy was based on clinical examination of the children and on data obtained from the questionnaires. The faecal microbiota were quantified by seeding serial dilutions on nine different media for incubation in different environment. The composition of the gut microbiota was expressed both as absolute counts of the various species and their relative share among the total counts of identified microbiota. Results Bifidobacteria were less commonly detected in children with allergic diseases than in healthy children and clostridia comprised a higher proportion among their gut microbes. Children with specific IgE antibodies to defined allergens had higher counts of clostridia and the counts of clostridia correlated with the level of serum IgE, but only so in allergic children. In non-allergic children, the serum IgE levels showed a positive correlation with the counts of bacteroides. Conclusion The development of allergic diseases seems to be associated with the composition of the gut microbial ecosystem. High counts of potential pathogens, such as clostridia, are associated with clinical manifestations of allergy and IgE antibody formation.. allergy| bacteroides| bifidobacteria| children| clostridia| gut microbiota| ige|atopic diseases| allergy| microflora| childhood| infants| exposure| bifidobacteria| sensitization| prevalence| antibodies.	SEP-2005	allergy| bacteroides| bifidobacteria| children| clostridia| gut microbiota| ige|atopic diseases| allergy| microflora| childhood| infants| exposure| bifidobacteria| sensitization| prevalence| antibodies	Sepp, E; Julge, K; Mikelsaar, M; Bjorksten, B	Intestinal microbiota and immunoglobulin E responses in 5-year-old Estonian children		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; bacteroides; bifidobacteria; children; clostridia; gut microbiota; IgE	ATOPIC DISEASES; ALLERGY; MICROFLORA; CHILDHOOD; INFANTS; EXPOSURE; BIFIDOBACTERIA; SENSITIZATION; PREVALENCE; ANTIBODIES	Background Over the last few decades, several studies from different parts of the world have indicated an increasing prevalence of allergic diseases. This has been related to environmental factors, like changes of microbial pressure. Our previous studies have demonstrated differences in the intestinal microbiota between allergic and non-allergic children. Aim To test the hypothesis that the intestinal microbiota and IgE response are related, both in allergic and non-allergic 5-year-old Estonian children. Methods The study group comprised 19 allergic and 19 non-allergic 5-year-old children, selected from a larger group who had been followed from birth. The diagnosis of allergy was based on clinical examination of the children and on data obtained from the questionnaires. The faecal microbiota were quantified by seeding serial dilutions on nine different media for incubation in different environment. The composition of the gut microbiota was expressed both as absolute counts of the various species and their relative share among the total counts of identified microbiota. Results Bifidobacteria were less commonly detected in children with allergic diseases than in healthy children and clostridia comprised a higher proportion among their gut microbes. Children with specific IgE antibodies to defined allergens had higher counts of clostridia and the counts of clostridia correlated with the level of serum IgE, but only so in allergic children. In non-allergic children, the serum IgE levels showed a positive correlation with the counts of bacteroides. Conclusion The development of allergic diseases seems to be associated with the composition of the gut microbial ecosystem. High counts of potential pathogens, such as clostridia, are associated with clinical manifestations of allergy and IgE antibody formation.	42	72	2005	6	10.1111/j.1365-2222.2005.02315.x	Allergy; Immunology
CD14 tobacco gene-environment interaction modifies asthma severity and Immunoglobulin E levels in Latinos with asthma. Background: A recent family-based genomewide screen revealed linkage between the 5q31 region and the diagnosis of asthma, but only in those exposed to environmental tobacco smoke (ETS). Among the candidate genes in this region is CD14. Methods: To determine whether polymorphisms in the CD14 gene are related to this gene-by-environment interaction in Latinos, we used both family-based and cross-sectional cohort analysis to test for interactions between CD14 genotypes/haplotypes, exposure to ETS, and asthma-related phenotypes in 659 Mexican and Puerto Rican families. Results: We identified 21 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs, -810, -159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma exposed to ETS, without regard to ethnicity, CD14 +1437 genotypes were associated with asthma severity. SNP +1437 GG or GC genotypes were significantly associated with lower baseline FEV1, using both family-based (p = 0.0009) and cross-sectional cohort (p 0.03) analyses. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, we found an interaction between plasma IgE levels, SNP -159 genotypes, and ETS exposure (p = 0.0002). The lowest IgE levels were in those subjects with the TT genotype and who were exposed to ETS regardless of ethnicity. Conclusions: Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS, which affects pulmonary function and IgE levels among Latinos with asthma.. asthma genetics| cd14| gene-environment interaction| ige| latinos| tobacco|menthol cigarette use| puerto-rican| promoter polymorphisms| childhood asthma| atopic diseases| passive smoking| soluble cd14| children| ige| association.	JUL 15-2005	asthma genetics| cd14| gene-environment interaction| ige| latinos| tobacco|menthol cigarette use| puerto-rican| promoter polymorphisms| childhood asthma| atopic diseases| passive smoking| soluble cd14| children| ige| association	Choudhry, S; Avila, PC; Nazario, S; Ung, N; Kho, J; Rodriguez-Santana, JR; Casal, J; Tsai, HJ; Torres, A; Ziv, E; Toscano, M; Sylvia, JS; Alioto, M; Salazar, M; Gomez, I; Fagan, JK; Salas, J; Lilly, C; Matallana, H; Castro, RA; Selman, M; Weiss, ST; Ford, JG; Drazen, JM; Rodriguez-Cintron, W; Chapela, R; Silverman, EK; Burchard, EG	CD14 tobacco gene-environment interaction modifies asthma severity and Immunoglobulin E levels in Latinos with asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma genetics; CD14; gene-environment interaction; IgE; Latinos; tobacco	MENTHOL CIGARETTE USE; PUERTO-RICAN; PROMOTER POLYMORPHISMS; CHILDHOOD ASTHMA; ATOPIC DISEASES; PASSIVE SMOKING; SOLUBLE CD14; CHILDREN; IGE; ASSOCIATION	Background: A recent family-based genomewide screen revealed linkage between the 5q31 region and the diagnosis of asthma, but only in those exposed to environmental tobacco smoke (ETS). Among the candidate genes in this region is CD14. Methods: To determine whether polymorphisms in the CD14 gene are related to this gene-by-environment interaction in Latinos, we used both family-based and cross-sectional cohort analysis to test for interactions between CD14 genotypes/haplotypes, exposure to ETS, and asthma-related phenotypes in 659 Mexican and Puerto Rican families. Results: We identified 21 single nucleotide polymorphisms (SNPs) in the CD14 gene by sequencing 72 Puerto Ricans, Mexicans, and African Americans with asthma. Three SNPs, -810, -159, and +1437, were further genotyped in families with asthma. Among all subjects with asthma exposed to ETS, without regard to ethnicity, CD14 +1437 genotypes were associated with asthma severity. SNP +1437 GG or GC genotypes were significantly associated with lower baseline FEV1, using both family-based (p = 0.0009) and cross-sectional cohort (p 0.03) analyses. Subjects with asthma with the GG or GC genotypes who were exposed to ETS had mean baseline FEV1 (% predicted) values 8.6% lower than subjects not exposed to ETS (p = 0.03). As previously observed in whites, we found an interaction between plasma IgE levels, SNP -159 genotypes, and ETS exposure (p = 0.0002). The lowest IgE levels were in those subjects with the TT genotype and who were exposed to ETS regardless of ethnicity. Conclusions: Our data suggest a gene-by-environment interaction between CD14 genotypes and ETS, which affects pulmonary function and IgE levels among Latinos with asthma.	51	72	2005	10	10.1164/rccm.200409-1232OC	General & Internal Medicine; Respiratory System
Food allergen sensitization in inner-city children with asthma. Background: Asthma continues to be an increasing cause of morbidity in the pediatric population, and studies have shown an association between food sensitivity and asthma. Objective: We investigated the degree of food allergen sensitization in inner-city patients with asthma. Methods: Five hundred four random serum samples from the National Cooperative Inner City Asthma Study were evaluated for specific IgE (UniCap) to 6 common food allergens (egg, milk, soy, peanut, wheat, and fish). Statistical analyses were performed to determine food sensitization prevalence and its association with asthma morbidity. Results: Forty-five percent of patients had evidence of sensitization (food-specific IgE &GE; 0.35 kU/L) to at least 1 food. Nineteen percent had IgE levels at &GE; 50% positive predictive value for clinical reactivity to at least 1 food, with 4% of patients having levels &GT; 95% positive predictive value for food allergy. Children sensitized to foods had higher rates of asthma hospitalization (P &LT; .01) and required more steroid medications (P = .025). Sensitization to foods also correlated with sensitization to more indoor and outdoor aeroallergens (P &LT; .001). Conclusion: Food allergen sensitization is highly prevalent in the inner-city population with asthma, and it is associated with increased asthma healthcare and medication use. Therefore, food allergen sensitivity may be a marker for increased asthma severity.. asthma| food allergy| sensitization| ige| inner-city children|manifestations.	MAY-2005	asthma| food allergy| sensitization| ige| inner-city children|manifestations	Wang, JL; Visness, CM; Sampson, HA	Food allergen sensitization in inner-city children with asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; food allergy; sensitization; IgE; inner-city children	MANIFESTATIONS	Background: Asthma continues to be an increasing cause of morbidity in the pediatric population, and studies have shown an association between food sensitivity and asthma. Objective: We investigated the degree of food allergen sensitization in inner-city patients with asthma. Methods: Five hundred four random serum samples from the National Cooperative Inner City Asthma Study were evaluated for specific IgE (UniCap) to 6 common food allergens (egg, milk, soy, peanut, wheat, and fish). Statistical analyses were performed to determine food sensitization prevalence and its association with asthma morbidity. Results: Forty-five percent of patients had evidence of sensitization (food-specific IgE &GE; 0.35 kU/L) to at least 1 food. Nineteen percent had IgE levels at &GE; 50% positive predictive value for clinical reactivity to at least 1 food, with 4% of patients having levels &GT; 95% positive predictive value for food allergy. Children sensitized to foods had higher rates of asthma hospitalization (P &LT; .01) and required more steroid medications (P = .025). Sensitization to foods also correlated with sensitization to more indoor and outdoor aeroallergens (P &LT; .001). Conclusion: Food allergen sensitization is highly prevalent in the inner-city population with asthma, and it is associated with increased asthma healthcare and medication use. Therefore, food allergen sensitivity may be a marker for increased asthma severity.	18	72	2005	5	10.1016/j.jaci.2005.02.014	Allergy; Immunology
Airborne mouse allergen in the homes of inner-city children with asthma. Background: Airborne mouse allergen has not previously been measured in inner-city homes, and its relationship to settled dust mouse allergen levels is unknown. Objective: To quantify airborne and settled dust Mus m 1 levels in homes of inner-city patients with asthma and to identify risk factors for mouse allergen exposure. Methods: One hundred inner-city school-age children with asthma in Baltimore underwent skin testing to a panel of aeroallergens, and their homes were inspected by a trained technician. Air and settled dust were sampled in the child's bedroom. Mus m 1, particulate matter smaller than 10 microns (PM10), and particulate matter smaller than 2.5 microns were quantified in air samples, and Mus m 1 was quantified in settled dust samples. Results: Mus m 1 was detected in settled dust samples from 100% of bedrooms. Airborne mouse allergen was detected in 48 of 57 (84%) bedrooms, and the median airborne mouse allergen concentration was 0.03 ng/m(3). The median PM10 concentration was 48 mug/m(3). Airborne and settled dust mouse allergen levels were moderately correlated (r = .52; P < .0001), and airborne Mus m 1 and PM10 levels were weakly correlated (r =.29; P = .03). Having cracks or holes in doors or walls, evidence of food remains in the kitchen, and mouse infestation were all independently associated with having detectable airborne mouse allergen. Conclusion: Airborne mouse allergen concentrations in many inner-city homes may be similar to those found in animal facilities, where levels are sufficiently high to elicit symptoms in sensitized individuals. Exposed food remains, cracks and holes in doors or walls, and evidence of mouse infestation appear to be risk factors for having detectable airborne Mus m 1.. mouse allergen| inner-city asthma| particulate matter| mus m 1|skin-test sensitivity| exposure| sensitization| prevalence| cats.	FEB-2005	mouse allergen| inner-city asthma| particulate matter| mus m 1|skin-test sensitivity| exposure| sensitization| prevalence| cats	Matsui, EC; Simons, E; Rand, C; Butz, A; Buckley, TJ; Breysse, P; Eggleston, PA	Airborne mouse allergen in the homes of inner-city children with asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	mouse allergen; inner-city asthma; particulate matter; Mus m 1	SKIN-TEST SENSITIVITY; EXPOSURE; SENSITIZATION; PREVALENCE; CATS	Background: Airborne mouse allergen has not previously been measured in inner-city homes, and its relationship to settled dust mouse allergen levels is unknown. Objective: To quantify airborne and settled dust Mus m 1 levels in homes of inner-city patients with asthma and to identify risk factors for mouse allergen exposure. Methods: One hundred inner-city school-age children with asthma in Baltimore underwent skin testing to a panel of aeroallergens, and their homes were inspected by a trained technician. Air and settled dust were sampled in the child's bedroom. Mus m 1, particulate matter smaller than 10 microns (PM10), and particulate matter smaller than 2.5 microns were quantified in air samples, and Mus m 1 was quantified in settled dust samples. Results: Mus m 1 was detected in settled dust samples from 100% of bedrooms. Airborne mouse allergen was detected in 48 of 57 (84%) bedrooms, and the median airborne mouse allergen concentration was 0.03 ng/m(3). The median PM10 concentration was 48 mug/m(3). Airborne and settled dust mouse allergen levels were moderately correlated (r = .52; P < .0001), and airborne Mus m 1 and PM10 levels were weakly correlated (r =.29; P = .03). Having cracks or holes in doors or walls, evidence of food remains in the kitchen, and mouse infestation were all independently associated with having detectable airborne mouse allergen. Conclusion: Airborne mouse allergen concentrations in many inner-city homes may be similar to those found in animal facilities, where levels are sufficiently high to elicit symptoms in sensitized individuals. Exposed food remains, cracks and holes in doors or walls, and evidence of mouse infestation appear to be risk factors for having detectable airborne Mus m 1.	16	72	2005	6	10.1016/j.jaci.2004.11.007	Allergy; Immunology
Pulmonary chemokine expression is coordinately regulated by STAT1, STAT6, and IFN-gamma. The expression of distinct chemokines within the asthmatic lung suggests that specific regulatory mechanisms may mediate various stages of asthmatic disease. Global transcript expression profiling was used to define the spectrum and kinetics of chemokine involvement in an experimental murine model of asthma. Seventeen chemokines were induced in the lungs of allergen-inoculated mice, as compared with saline-treated mice. Two (CXCL13 and CCL9) of the 17 identified chemokines have not previously been associated with allergic airway disease. Seven (7 of 17; CCL2, CCL7, CCL9, CCL11, CXCL1, CXCL5, CXCL10) of the allergen-induced chemokines were induced early after allergen challenge and remained induced throughout the experimental period. Three chemokines (CXCL2, CCL3, and CCL17) were induced only during the early phase of the inflammatory response after the initial allergen challenge, while seven chemokines (CCL6, CCL8, CCL12, CCL22, CXCL9, CXCL12, and CXCL13) were increased only after a second allergen exposure. Unexpectedly, expression of only three chemokines, CCL11, CCL17, and CCL22, was STAT6 dependent, and many of the identified chemokines were overexpressed in STAT6-deficient mice, providing an explanation for the enhanced neutrophilic inflammation seen in these mice. Notably, IFN-gamma and STAT1 were shown to contribute to the induction of two STAT6-independent chemokines, CXCL9 and CXCL10. Taken together, these results show that only a select panel of chemokines (those targeting Th2 cells and eosinophils) is positively regulated by STAT6; instead, many of the allergen-induced chemokines are negatively regulated by STAT6. Collectively, we demonstrate that allergen-induced inflammation involves coordinate regulation by STAT1, STAT6, and IFN-gamma.. socs-1 gene-expression| airway inflammation| t-cells| eosinophilic inflammation| experimental asthma| eotaxin expression| epithelial-cells| mucus production| tnf-alpha| th2 cells.	DEC 15-2004	socs-1 gene-expression| airway inflammation| t-cells| eosinophilic inflammation| experimental asthma| eotaxin expression| epithelial-cells| mucus production| tnf-alpha| th2 cells	Fulkerson, PC; Zimmermann, N; Hassman, LM; Finkelman, FD; Rothenberg, ME	Pulmonary chemokine expression is coordinately regulated by STAT1, STAT6, and IFN-gamma		JOURNAL OF IMMUNOLOGY		SOCS-1 GENE-EXPRESSION; AIRWAY INFLAMMATION; T-CELLS; EOSINOPHILIC INFLAMMATION; EXPERIMENTAL ASTHMA; EOTAXIN EXPRESSION; EPITHELIAL-CELLS; MUCUS PRODUCTION; TNF-ALPHA; TH2 CELLS	The expression of distinct chemokines within the asthmatic lung suggests that specific regulatory mechanisms may mediate various stages of asthmatic disease. Global transcript expression profiling was used to define the spectrum and kinetics of chemokine involvement in an experimental murine model of asthma. Seventeen chemokines were induced in the lungs of allergen-inoculated mice, as compared with saline-treated mice. Two (CXCL13 and CCL9) of the 17 identified chemokines have not previously been associated with allergic airway disease. Seven (7 of 17; CCL2, CCL7, CCL9, CCL11, CXCL1, CXCL5, CXCL10) of the allergen-induced chemokines were induced early after allergen challenge and remained induced throughout the experimental period. Three chemokines (CXCL2, CCL3, and CCL17) were induced only during the early phase of the inflammatory response after the initial allergen challenge, while seven chemokines (CCL6, CCL8, CCL12, CCL22, CXCL9, CXCL12, and CXCL13) were increased only after a second allergen exposure. Unexpectedly, expression of only three chemokines, CCL11, CCL17, and CCL22, was STAT6 dependent, and many of the identified chemokines were overexpressed in STAT6-deficient mice, providing an explanation for the enhanced neutrophilic inflammation seen in these mice. Notably, IFN-gamma and STAT1 were shown to contribute to the induction of two STAT6-independent chemokines, CXCL9 and CXCL10. Taken together, these results show that only a select panel of chemokines (those targeting Th2 cells and eosinophils) is positively regulated by STAT6; instead, many of the allergen-induced chemokines are negatively regulated by STAT6. Collectively, we demonstrate that allergen-induced inflammation involves coordinate regulation by STAT1, STAT6, and IFN-gamma.	54	72	2004	10		Immunology
Individualised unsupervised exercise training in adults with cystic fibrosis: a 1 year randomised controlled trial. Background: Short term studies of exercise training have shown benefits in cystic fibrosis. Transferring exercise programmes to the community and sustaining them long term is a challenge for the patient. The effectiveness of an individualised unsupervised home based exercise programme was examined in adults with cystic fibrosis over a 1 year period. Methods: Subjects were randomised to undertake three sessions per week of upper and lower body exercise based on individualised preferences (n = 30) or to a control group ( n = 18). They were evaluated at baseline and at 12 months. The primary outcome measure was improved fitness as assessed by change in blood lactate concentration at the end of an identical constant work rate for both arm and leg ergometric testing. Secondary outcome measurements were heart rate and pulmonary function. Results: For leg exercise, significant differences were seen at 12 months between the active and control groups in the mean (SE) change in blood lactate levels (-0.38 (0.23) mmol/l v 0.45 (0.25) mmol/l, p<0.05) and heart rate (-4.8 (2.5) bpm v 3.4 (2.5) bpm, p<0.05), confirming a training effect. For arm ergometry there was no change in lactate levels at 12 months but there was a significant difference in forced vital capacity (46 (72) ml v -167 (68) ml, p<0.05). Conclusions: A training effect, as measured by a reduction in lactate levels and heart rate, can be achieved with unsupervised individualised home exercise in adults with cystic fibrosis. A benefit to pulmonary function was observed and together these findings suggest that exercise programmes should be encouraged as an important component of care in cystic fibrosis.. pulmonary-function| lung-function| children| program| tolerance| capacity| asthma.	DEC-2004	pulmonary-function| lung-function| children| program| tolerance| capacity| asthma	Moorcroft, AJ; Dodd, ME; Morris, J; Webb, AK	Individualised unsupervised exercise training in adults with cystic fibrosis: a 1 year randomised controlled trial		THORAX		PULMONARY-FUNCTION; LUNG-FUNCTION; CHILDREN; PROGRAM; TOLERANCE; CAPACITY; ASTHMA	Background: Short term studies of exercise training have shown benefits in cystic fibrosis. Transferring exercise programmes to the community and sustaining them long term is a challenge for the patient. The effectiveness of an individualised unsupervised home based exercise programme was examined in adults with cystic fibrosis over a 1 year period. Methods: Subjects were randomised to undertake three sessions per week of upper and lower body exercise based on individualised preferences (n = 30) or to a control group ( n = 18). They were evaluated at baseline and at 12 months. The primary outcome measure was improved fitness as assessed by change in blood lactate concentration at the end of an identical constant work rate for both arm and leg ergometric testing. Secondary outcome measurements were heart rate and pulmonary function. Results: For leg exercise, significant differences were seen at 12 months between the active and control groups in the mean (SE) change in blood lactate levels (-0.38 (0.23) mmol/l v 0.45 (0.25) mmol/l, p<0.05) and heart rate (-4.8 (2.5) bpm v 3.4 (2.5) bpm, p<0.05), confirming a training effect. For arm ergometry there was no change in lactate levels at 12 months but there was a significant difference in forced vital capacity (46 (72) ml v -167 (68) ml, p<0.05). Conclusions: A training effect, as measured by a reduction in lactate levels and heart rate, can be achieved with unsupervised individualised home exercise in adults with cystic fibrosis. A benefit to pulmonary function was observed and together these findings suggest that exercise programmes should be encouraged as an important component of care in cystic fibrosis.	34	72	2004	7	10.1136/thx.2003.015313	Respiratory System
Umbilical cord and maternal blood red cell fatty acids and early childhood wheezing and eczema. Background: Few studies have explored whether fetal exposure to n-6 and n-3 fatty acids influences the inception of atopic disease. Objective: To assess prenatal fatty acid exposures as predictors of early childhood wheezing and eczema. Methods: In the Avon Longitudinal Study of Parents and Children, late pregnancy maternal blood samples and umbilical cord blood samples were assayed for n-6 and n-3 fatty acids (percentage of total red cell phospholipid), and mothers were asked about wheezing and eczema in their children. We measured associations of 11 n-6 and n-3 fatty acid exposures with wheezing at 30 to 42 months, with wheezing patterns defined by presence (+) or absence (-) of wheezing during 2 periods, 0 to 6 months and 30 to 42 months (transient infant, +/-; later-onset, -/+; persistent, +/+; n = 1191 and n = 2764 for cord and maternal analyses, respectively), and with eczema at 18 to 30 months (n = 1238 and n = 2945 for cord and maternal analyses, respectively). Results: In cord blood red cells, the ratio of arachidonic:eicosapentaenoic acid was positively associated with eczema (adjusted odds ratio [OR] per doubling, 1.14; 95% CI, 1.00-1.31; P = .044), the ratio of linoleic acid: a-linolenic acid was positively associated with later-onset wheeze (OR, 1.30; CI, 1.04-1.61; P = .019), and the ratio of a-linolenic acid:n-3 products was negatively associated with later-onset wheeze (OR, 0.86; CI, 0.75-0.99; P = .040). However, these associations were no longer significant after adjusting for multiple comparisons. Conclusions: It seems unlikely that fetal exposure to n-6 and n-3 fatty acids is an important determinant of early childhood wheezing and atopic disease.. n-3/n-6 fatty acids| wheezing| eczema| birth cohort| prenatal|airway responses| atopic disease| birth-weight| children| prostaglandin-e2| allergy| lymphocytes| pregnancy| gamma| risk.	SEP-2004	n-3/n-6 fatty acids| wheezing| eczema| birth cohort| prenatal|airway responses| atopic disease| birth-weight| children| prostaglandin-e2| allergy| lymphocytes| pregnancy| gamma| risk	Newson, RB; Shaheen, SO; Henderson, AJ; Emmett, PM; Sherriff, A; Calder, PC	Umbilical cord and maternal blood red cell fatty acids and early childhood wheezing and eczema		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	n-3/n-6 Fatty acids; wheezing; eczema; birth cohort; prenatal	AIRWAY RESPONSES; ATOPIC DISEASE; BIRTH-WEIGHT; CHILDREN; PROSTAGLANDIN-E2; ALLERGY; LYMPHOCYTES; PREGNANCY; GAMMA; RISK	Background: Few studies have explored whether fetal exposure to n-6 and n-3 fatty acids influences the inception of atopic disease. Objective: To assess prenatal fatty acid exposures as predictors of early childhood wheezing and eczema. Methods: In the Avon Longitudinal Study of Parents and Children, late pregnancy maternal blood samples and umbilical cord blood samples were assayed for n-6 and n-3 fatty acids (percentage of total red cell phospholipid), and mothers were asked about wheezing and eczema in their children. We measured associations of 11 n-6 and n-3 fatty acid exposures with wheezing at 30 to 42 months, with wheezing patterns defined by presence (+) or absence (-) of wheezing during 2 periods, 0 to 6 months and 30 to 42 months (transient infant, +/-; later-onset, -/+; persistent, +/+; n = 1191 and n = 2764 for cord and maternal analyses, respectively), and with eczema at 18 to 30 months (n = 1238 and n = 2945 for cord and maternal analyses, respectively). Results: In cord blood red cells, the ratio of arachidonic:eicosapentaenoic acid was positively associated with eczema (adjusted odds ratio [OR] per doubling, 1.14; 95% CI, 1.00-1.31; P = .044), the ratio of linoleic acid: a-linolenic acid was positively associated with later-onset wheeze (OR, 1.30; CI, 1.04-1.61; P = .019), and the ratio of a-linolenic acid:n-3 products was negatively associated with later-onset wheeze (OR, 0.86; CI, 0.75-0.99; P = .040). However, these associations were no longer significant after adjusting for multiple comparisons. Conclusions: It seems unlikely that fetal exposure to n-6 and n-3 fatty acids is an important determinant of early childhood wheezing and atopic disease.	29	72	2004	7	10.1016/j.jaci.2004.05.010	Allergy; Immunology
Factors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey. Objective To determine the factors associated with difference in prevalence of asthma in children in different regions of China. Design Multicentre epidemiological survey. Setting Three cities in china. Participants 10 902 schoolchildren aged 10 years. Main outcome measures Asthma and atopic symptoms, atopic sensitisation, and early and current exposure to environmental factors. Results Children from Hong Kong had a significantly higher prevalence of wheeze in the past year than those from Guangzhou and Beijing (odds ratio 1.64, 95% confidence interval 1.35 to 1.99). Factors during the first year of life and currently that were significantly associated with wheeze were cooking with gas (odds ratio 2.04, 1.34 to 3.13), foam pillows (2.58, 1.66 to 3.99), and damp housing (1.89,1.26 to 2.83). Factors protecting against wheeze were cotton quilts and the consumption of fruit and raw vegetables. Conclusion Environmental factors and diet may explain the differences in prevalence of asthma between children living in different regions of China.. respiratory symptoms| childhood asthma| home-environment| lung-function| young-adults| schoolchildren| population| risk.	AUG 28-2004	respiratory symptoms| childhood asthma| home-environment| lung-function| young-adults| schoolchildren| population| risk	Wong, GWK; Ko, FWS; Hui, DSC; Fok, TF; Carr, D; von Mutius, E; Zhong, NS; Chen, YZ; Lai, CKW	Factors associated with difference in prevalence of asthma in children from three cities in China: multicentre epidemiological survey		BRITISH MEDICAL JOURNAL		RESPIRATORY SYMPTOMS; CHILDHOOD ASTHMA; HOME-ENVIRONMENT; LUNG-FUNCTION; YOUNG-ADULTS; SCHOOLCHILDREN; POPULATION; RISK	Objective To determine the factors associated with difference in prevalence of asthma in children in different regions of China. Design Multicentre epidemiological survey. Setting Three cities in china. Participants 10 902 schoolchildren aged 10 years. Main outcome measures Asthma and atopic symptoms, atopic sensitisation, and early and current exposure to environmental factors. Results Children from Hong Kong had a significantly higher prevalence of wheeze in the past year than those from Guangzhou and Beijing (odds ratio 1.64, 95% confidence interval 1.35 to 1.99). Factors during the first year of life and currently that were significantly associated with wheeze were cooking with gas (odds ratio 2.04, 1.34 to 3.13), foam pillows (2.58, 1.66 to 3.99), and damp housing (1.89,1.26 to 2.83). Factors protecting against wheeze were cotton quilts and the consumption of fruit and raw vegetables. Conclusion Environmental factors and diet may explain the differences in prevalence of asthma between children living in different regions of China.	23	72	2004	5	10.1136/bmj.329.7464.486	General & Internal Medicine
A prospective study of Fel d1 and Der p1 exposure in infancy land childhood wheezing. The impact of domestic exposure to cat allergen (Fel d1) and house dust mite (Der p1) on wheezing from birth to the age of 4 years was investigated in a multicenter prospective birth cohort; 1,611 mothers were recruited before delivery in Ashford, England, and Barcelona and Menorca, Spain. Exposures were gathered via dust sample collection at children's home in their first year of life. Families provided complete outcome data (wheezing status in all 4 years) for 1,289 children. Domestic allergen levels varied substantially between centers. Six hundred three (47%) children never wheezed during their first 4 years of life. Der p1 did not correlate with any type of wheezing outcome. Fel d1 significantly increased the risk of wheezing in 3- and 4-year-olds in comparison to 1-year-olds. Distinct risk profiles were found for wheezing at different ages. Multivariate analysis revealed an interaction between Fel d1 and maternal asthma among children who wheeze in Year 4 (relative risk = 2.77; 95% confidence interval = 1.19-6.46). Our data support the idea that several patterns of wheezing with different risk profiles exist among young children. The effect of Fel d1 exposure varied according to age and maternal asthma.. allergens cohort| infants| wheezing|house-dust mite| environmental risk-factors| allergen exposure| cat allergen| asthma| children| sensitization| life| symptoms| fel-d-1.	AUG 1-2004	allergens cohort| infants| wheezing|house-dust mite| environmental risk-factors| allergen exposure| cat allergen| asthma| children| sensitization| life| symptoms| fel-d-1	Polk, S; Sunyer, J; Munoz-Ortiz, L; Barnes, M; Torrent, M; Figueroa, C; Harris, J; Vall, O; Anto, JM; Cullinan, P	A prospective study of Fel d1 and Der p1 exposure in infancy land childhood wheezing		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	allergens cohort; infants; wheezing	HOUSE-DUST MITE; ENVIRONMENTAL RISK-FACTORS; ALLERGEN EXPOSURE; CAT ALLERGEN; ASTHMA; CHILDREN; SENSITIZATION; LIFE; SYMPTOMS; FEL-D-1	The impact of domestic exposure to cat allergen (Fel d1) and house dust mite (Der p1) on wheezing from birth to the age of 4 years was investigated in a multicenter prospective birth cohort; 1,611 mothers were recruited before delivery in Ashford, England, and Barcelona and Menorca, Spain. Exposures were gathered via dust sample collection at children's home in their first year of life. Families provided complete outcome data (wheezing status in all 4 years) for 1,289 children. Domestic allergen levels varied substantially between centers. Six hundred three (47%) children never wheezed during their first 4 years of life. Der p1 did not correlate with any type of wheezing outcome. Fel d1 significantly increased the risk of wheezing in 3- and 4-year-olds in comparison to 1-year-olds. Distinct risk profiles were found for wheezing at different ages. Multivariate analysis revealed an interaction between Fel d1 and maternal asthma among children who wheeze in Year 4 (relative risk = 2.77; 95% confidence interval = 1.19-6.46). Our data support the idea that several patterns of wheezing with different risk profiles exist among young children. The effect of Fel d1 exposure varied according to age and maternal asthma.	34	72	2004	6	10.1164/rccm.200310-1348OC	General & Internal Medicine; Respiratory System
Cow's milk-specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10. Background: The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood. Objective: The cow's milk-specific T-cell response of donors with various allergic backgrounds was investigated. Methods: Cow's milk-specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk-tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status. Results: Cow's milk-specific TCCs of children with persistent CMA were T(H)2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-gamma and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25. Conclusion: The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milk-tolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-gamma. These findings suggest that activated CD4(+) T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of IL-10.. antigen-specific t cells| cow's milk| food allergy| tolerance| il-10|house-dust mite| atopic-dermatitis| lymphocyte-responses| peripheral-blood| dietary antigen| food allergy| interleukin-10| expression| tolerance| asthma.	MAY-2004	antigen-specific t cells| cow's milk| food allergy| tolerance| il-10|house-dust mite| atopic-dermatitis| lymphocyte-responses| peripheral-blood| dietary antigen| food allergy| interleukin-10| expression| tolerance| asthma	Tiemessen, MM; Van Leperen-Van Dijk, AG; Bruijnzeel-Koomen, CAFM; Garssen, J; Knol, EF; Van Hoffen, E	Cow's milk-specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	antigen-specific T cells; cow's milk; food allergy; tolerance; IL-10	HOUSE-DUST MITE; ATOPIC-DERMATITIS; LYMPHOCYTE-RESPONSES; PERIPHERAL-BLOOD; DIETARY ANTIGEN; FOOD ALLERGY; INTERLEUKIN-10; EXPRESSION; TOLERANCE; ASTHMA	Background: The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood. Objective: The cow's milk-specific T-cell response of donors with various allergic backgrounds was investigated. Methods: Cow's milk-specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk-tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status. Results: Cow's milk-specific TCCs of children with persistent CMA were T(H)2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-gamma and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25. Conclusion: The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milk-tolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-gamma. These findings suggest that activated CD4(+) T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of IL-10.	30	72	2004	8	10.1016/j.jaci.2003.12.016	Allergy; Immunology
Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth. Studying the effect of maternal asthma during pregnancy on placental function and fetal development has highlighted that there is a strong interaction between mother, placenta and fetus and these interactions appear to be sex-specific. This work has found that the female fetus alters maternal asthma during pregnancy by upregulating maternal inflammatory pathways. When asthma-associated inflammatory pathways are not treated with inhaled steroids during pregnancy, the female fetus has reduced growth and adrenal function due to alterations in placental glucocorticold metabolism. When the mother uses inhaled steroid for the treatment of her asthma during pregnancy, female fetal growth and placental function are comparable to the control population. The growth of the male fetus appears to be unaffected by asthma or inhaled steroid use. These findings indicate there may be different mechanisms regulating placental glucocorticoid and immune mechanisms depending on fetal sex in both asthmatic and non-asthmatic pregnancies. (C) 2004 IFPA and Elsevier Ltd. All rights reserved.. 11-beta-hydroxysteroid dehydrogenase type-2| glucocorticoid exposure| alveolar macrophages| intrauterine growth| blood monocytes| human-pregnancy| atopic disease| messenger-rna| immune-system| t-cells.	APR-2004	11-beta-hydroxysteroid dehydrogenase type-2| glucocorticoid exposure| alveolar macrophages| intrauterine growth| blood monocytes| human-pregnancy| atopic disease| messenger-rna| immune-system| t-cells	Clifton, VL; Murphy, VE	Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth		PLACENTA		11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-2; GLUCOCORTICOID EXPOSURE; ALVEOLAR MACROPHAGES; INTRAUTERINE GROWTH; BLOOD MONOCYTES; HUMAN-PREGNANCY; ATOPIC DISEASE; MESSENGER-RNA; IMMUNE-SYSTEM; T-CELLS	Studying the effect of maternal asthma during pregnancy on placental function and fetal development has highlighted that there is a strong interaction between mother, placenta and fetus and these interactions appear to be sex-specific. This work has found that the female fetus alters maternal asthma during pregnancy by upregulating maternal inflammatory pathways. When asthma-associated inflammatory pathways are not treated with inhaled steroids during pregnancy, the female fetus has reduced growth and adrenal function due to alterations in placental glucocorticold metabolism. When the mother uses inhaled steroid for the treatment of her asthma during pregnancy, female fetal growth and placental function are comparable to the control population. The growth of the male fetus appears to be unaffected by asthma or inhaled steroid use. These findings indicate there may be different mechanisms regulating placental glucocorticoid and immune mechanisms depending on fetal sex in both asthmatic and non-asthmatic pregnancies. (C) 2004 IFPA and Elsevier Ltd. All rights reserved.	55	72	2004	8	10.1016/j.placenta.2004.01.004	Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing. The fat soluble vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D-3], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH)(2)D-3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)(2)D-3 has anti-inflammatory effects in an in vivo Th2-dependent asthma model. In addition, we demonstrate that 1,25(OH)(2)D-3 down-regulates the cytoskeleton rearrangement required for promoting integrin-mediated adhesion of naive and effector CD4(+) T cells. Finally, 1,25(OH)(2)D-3 inhibits chemokine-induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)(2)D-3 regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation.. cd4 t cells| th2 cells| vitamin d| asthma| cytoskeleton rearrangement| migration|high endothelial venules| dendritic cells| ifn-gamma| receptor expression| immune-response| b-cells| d-3| activation| mice| inhibition.	APR-2004	cd4 t cells| th2 cells| vitamin d| asthma| cytoskeleton rearrangement| migration|high endothelial venules| dendritic cells| ifn-gamma| receptor expression| immune-response| b-cells| d-3| activation| mice| inhibition	Topilski, I; Flaishon, L; Naveh, Y; Harmelin, A; Levo, Y; Shachar, I	The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing		EUROPEAN JOURNAL OF IMMUNOLOGY	CD4 T cells; Th2 cells; vitamin D; asthma; cytoskeleton rearrangement; migration	HIGH ENDOTHELIAL VENULES; DENDRITIC CELLS; IFN-GAMMA; RECEPTOR EXPRESSION; IMMUNE-RESPONSE; B-CELLS; D-3; ACTIVATION; MICE; INHIBITION	The fat soluble vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D-3], and its nuclear receptor play an important role in regulating immune responses. While 1,25(OH)(2)D-3 is known to inhibit transcription of cytokine genes that are required for Th1 differentiation or are products of differentiated Th1 cells, its role in regulating differentiation of Th2 cells is less clear. In this study, we show that 1,25(OH)(2)D-3 has anti-inflammatory effects in an in vivo Th2-dependent asthma model. In addition, we demonstrate that 1,25(OH)(2)D-3 down-regulates the cytoskeleton rearrangement required for promoting integrin-mediated adhesion of naive and effector CD4(+) T cells. Finally, 1,25(OH)(2)D-3 inhibits chemokine-induced migration of naive cells and their homing to the lymph nodes. Thus, in addition to its regulation of cytokine transcription, 1,25(OH)(2)D-3 regulates migration of cells and thus controls the skewing of various Th subsets in the secondary lymphoid organs and inhibits Th function at sites of inflammation.	52	72	2004	9	10.1002/eji.200324532	Immunology
Occupation and asthma: A population-based incident case-control study. The authors assessed the relations between occupation and risk of developing asthma in adulthood in a 1997-2000 population-based incident case-control study of 521 cases and 932 controls in south Finland. The occupations were classified according to potential exposure to asthma-causing inhalants. Asthma risk was increased consistently for both men and women in the chemical (adjusted odds ratio (OR) = 5.69, 95% confidence interval (CI): 1.08, 29.8), rubber and plastic (OR = 2.61, 95% CI: 0.92, 7.42), and wood and paper (OR = 1.72, 95% CI: 0.71, 4.17) industries. Risk in relation to occupation was increased only for men-for bakers and food processors (OR = 8.62, 95% CI: 0.86, 86.5), textile workers (OR = 4.70, 95% CI: 0.29, 77.1), electrical and electronic production workers (OR 2.83, 95% CI: 0.82, 6.93), laboratory technicians (OR = 1.66, 95% CI: 0.17, 16.6), and storage workers (OR 1.57, 95% CI: 0.40, 6.19). Of the predominantly men's occupations, metal (OR = 4.52, 95% CI: 2.35, 8.70) and forestry (OR = 6.00, 95% CI: 0.96, 37.5) work were the strongest determinants of asthma. For women, asthma risk increased for waiters (OR = 3.03, 95% CI: 1.10, 8.31), cleaners (OR = 1.42, 95% CI: 0.81, 2.48), and dental workers (OR = 4.74, 95% CI: 0.48, 46.5). Results suggest an increased asthma risk both in traditional industries and forestry and in several nonindustrial occupations.. asthma| case-control studies| occupational diseases| occupations|malodorous sulfur-compounds| karelia air-pollution| adult-onset asthma| respiratory symptoms| general-population| exposure| community| sample| risk.	NOV 15-2003	asthma| case-control studies| occupational diseases| occupations|malodorous sulfur-compounds| karelia air-pollution| adult-onset asthma| respiratory symptoms| general-population| exposure| community| sample| risk	Jaakkola, JJK; Piipari, R; Jaakkola, MS	Occupation and asthma: A population-based incident case-control study		AMERICAN JOURNAL OF EPIDEMIOLOGY	asthma; case-control studies; occupational diseases; occupations	MALODOROUS SULFUR-COMPOUNDS; KARELIA AIR-POLLUTION; ADULT-ONSET ASTHMA; RESPIRATORY SYMPTOMS; GENERAL-POPULATION; EXPOSURE; COMMUNITY; SAMPLE; RISK	The authors assessed the relations between occupation and risk of developing asthma in adulthood in a 1997-2000 population-based incident case-control study of 521 cases and 932 controls in south Finland. The occupations were classified according to potential exposure to asthma-causing inhalants. Asthma risk was increased consistently for both men and women in the chemical (adjusted odds ratio (OR) = 5.69, 95% confidence interval (CI): 1.08, 29.8), rubber and plastic (OR = 2.61, 95% CI: 0.92, 7.42), and wood and paper (OR = 1.72, 95% CI: 0.71, 4.17) industries. Risk in relation to occupation was increased only for men-for bakers and food processors (OR = 8.62, 95% CI: 0.86, 86.5), textile workers (OR = 4.70, 95% CI: 0.29, 77.1), electrical and electronic production workers (OR 2.83, 95% CI: 0.82, 6.93), laboratory technicians (OR = 1.66, 95% CI: 0.17, 16.6), and storage workers (OR 1.57, 95% CI: 0.40, 6.19). Of the predominantly men's occupations, metal (OR = 4.52, 95% CI: 2.35, 8.70) and forestry (OR = 6.00, 95% CI: 0.96, 37.5) work were the strongest determinants of asthma. For women, asthma risk increased for waiters (OR = 3.03, 95% CI: 1.10, 8.31), cleaners (OR = 1.42, 95% CI: 0.81, 2.48), and dental workers (OR = 4.74, 95% CI: 0.48, 46.5). Results suggest an increased asthma risk both in traditional industries and forestry and in several nonindustrial occupations.	28	72	2003	7	10.1093/aje/kwg238	Public, Environmental & Occupational Health
Asthma symptoms in women employed in domestic cleaning: a community based study. Background: Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. The aim of this study was to assess the risk of asthma in women employed in domestic cleaning. Methods: A cross sectional study was conducted in 4521 women aged 30 to 65 years. Information on respiratory symptoms and cleaning work history was obtained using a postal questionnaire with telephone follow up. Asthma was defined as reported symptoms in the last year or current use of drugs to treat asthma. Odds ratios (OR) with 95% confidence intervals (CI) for asthma in different cleaning groups were estimated using adjusted unconditional logistic regression models. Results: 593 women (13%) were currently employed in domestic cleaning work. Asthma was more prevalent in this group than in women who had never worked in cleaning (OR 1.46 (95% CI, 1.10 to 1.92)). Former domestic cleaning work was reported by 1170 women (26%), and was strongly associated with asthma (OR 2.09 (1.70 to 2.57)). Current and former non-domestic cleaning work was not significantly associated with asthma. Consistent results were obtained for other respiratory symptoms. Twenty five per cent of the asthma cases in the study population were attributable to domestic cleaning work. Conclusions: Employment in domestic cleaning may induce or aggravate asthma. This study suggests that domestic cleaning work has an important public health impact, probably involving not only professional cleaners but also people undertaking cleaning tasks at home.. occupational asthma| exposure| risk| work| cleaners.	NOV 1-2003	occupational asthma| exposure| risk| work| cleaners	Medina-Ramon, M; Zock, JP; Kogevinas, M; Sunyer, J; Anto, JM	Asthma symptoms in women employed in domestic cleaning: a community based study		THORAX		OCCUPATIONAL ASTHMA; EXPOSURE; RISK; WORK; CLEANERS	Background: Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. The aim of this study was to assess the risk of asthma in women employed in domestic cleaning. Methods: A cross sectional study was conducted in 4521 women aged 30 to 65 years. Information on respiratory symptoms and cleaning work history was obtained using a postal questionnaire with telephone follow up. Asthma was defined as reported symptoms in the last year or current use of drugs to treat asthma. Odds ratios (OR) with 95% confidence intervals (CI) for asthma in different cleaning groups were estimated using adjusted unconditional logistic regression models. Results: 593 women (13%) were currently employed in domestic cleaning work. Asthma was more prevalent in this group than in women who had never worked in cleaning (OR 1.46 (95% CI, 1.10 to 1.92)). Former domestic cleaning work was reported by 1170 women (26%), and was strongly associated with asthma (OR 2.09 (1.70 to 2.57)). Current and former non-domestic cleaning work was not significantly associated with asthma. Consistent results were obtained for other respiratory symptoms. Twenty five per cent of the asthma cases in the study population were attributable to domestic cleaning work. Conclusions: Employment in domestic cleaning may induce or aggravate asthma. This study suggests that domestic cleaning work has an important public health impact, probably involving not only professional cleaners but also people undertaking cleaning tasks at home.	23	72	2003	5	10.1136/thorax.58.11.950	Respiratory System
Genetics and genomics of asthma and allergic diseases. Asthma and eczema (atopic dermatitis) are characterized by a number of unexplained phenomena: the familial aggregation of disease, the initiation of disease by apparently trivial exposure to allergens, the preferential transmission of disease from affected mothers and the large increase in prevalence of disease in Westernized societies in the last century. A number of genes and chromosomal regions have been identified that consistently show linkage to asthma and its related phenotypes. Known loci modify the strength of the atopic response, nonspecific inflammation, the ability to respond to particular allergens and nonspecific airway reactivity. Eczema has been shown to be due to a different set of genetic loci that are shared with other skin diseases such as psoriasis and leprosy. Genetic and genomic studies both provide evidence that epithelial surfaces are active in the induction of allergic disease.. fc-epsilon-ri| chronic lymphocytic-leukemia| inflammatory bowel-disease| immunoglobulin-e responses| calcium-binding protein| major susceptibility locus| atopic-dermatitis| wide search| beta-subunit| rheumatoid-arthritis.	DEC-2002	fc-epsilon-ri| chronic lymphocytic-leukemia| inflammatory bowel-disease| immunoglobulin-e responses| calcium-binding protein| major susceptibility locus| atopic-dermatitis| wide search| beta-subunit| rheumatoid-arthritis	Cookson, W	Genetics and genomics of asthma and allergic diseases		IMMUNOLOGICAL REVIEWS		FC-EPSILON-RI; CHRONIC LYMPHOCYTIC-LEUKEMIA; INFLAMMATORY BOWEL-DISEASE; IMMUNOGLOBULIN-E RESPONSES; CALCIUM-BINDING PROTEIN; MAJOR SUSCEPTIBILITY LOCUS; ATOPIC-DERMATITIS; WIDE SEARCH; BETA-SUBUNIT; RHEUMATOID-ARTHRITIS	Asthma and eczema (atopic dermatitis) are characterized by a number of unexplained phenomena: the familial aggregation of disease, the initiation of disease by apparently trivial exposure to allergens, the preferential transmission of disease from affected mothers and the large increase in prevalence of disease in Westernized societies in the last century. A number of genes and chromosomal regions have been identified that consistently show linkage to asthma and its related phenotypes. Known loci modify the strength of the atopic response, nonspecific inflammation, the ability to respond to particular allergens and nonspecific airway reactivity. Eczema has been shown to be due to a different set of genetic loci that are shared with other skin diseases such as psoriasis and leprosy. Genetic and genomic studies both provide evidence that epithelial surfaces are active in the induction of allergic disease.	178	72	2002	12	10.1034/j.1600-065X.2002.19015.x	Immunology
The impact of climate and traffic-related NO2 on the prevalence of asthma and allergic rhinitis in Italy. Background Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies. Aim To evaluate to what extent climate and outdoor NO2 pollution can explain the geographical variation in the prevalence of asthma and allergic rhinitis, and to estimate the relative risk for exposure to different levels of these two factors. Methods The impact of climate and long-term exposure to nitrogen dioxide (NO2) pollution on asthma and allergic rhinitis was assessed in a cross-sectional study, carried out during 1998 to 2000 on young adults aged 20 to 44 years (n = 18 873), living in 13 areas from two different Italian climatic regions (subcontinental and Mediterranean). Results Mediterranean areas had a significantly higher prevalence of asthma-like symptoms (P < 0.001), higher annual mean temperature (16.2 degreesC vs. 12.9 degreesC), lower temperature range (16.0 Cdegrees vs. 22.1 Cdegrees) and lower NO2 levels (31.46 mug/m(3) vs. 57.99 mug/m(3)) than subcontinental ones. Mediterranean climate was associated with an increased risk of wheeze (OR = 1.23; 95% CI 1.13 to 1.35), tightness in the chest (OR = 1.21; 95% CI 1.11 to 1.33), shortness of breath (OR = 1.21; 95% CI 1.08 to 1.36) and asthma attacks (OR = 1.19; 95% CI 1.07 to 1.31). After adjusting for climate, an increase of 18.3 mug/m(3) in NO2 levels moderately increased the risk of asthma attacks (OR = 1.13; 95% CI 0.98 to 1.32), tightness in the chest (OR = 1.11; 95% CI 0.98 to 1.26) and wheeze (OR = 1.11; 95% CI 0.96 to 1.28). When the levels of outdoor NO2 exposure rose, the prevalence of allergic rhinitis increased significantly in the Mediterranean region (OR = 1.38; 95% CI 1.12 to 1.69), but not in the subcontinental one (OR = 1.03; 95% CI 0.83 to 1.28). Conclusion Our results show that the prevalence of asthma increases when annual mean temperature increases and temperature range decreases. Furthermore, climate interacts with NO2 outdoor exposure, increasing the risk for allergic rhinitis in people exposed to high stable temperatures. A long-term role for the effect of traffic pollution on asthma is also suggested.. allergic rhinitis| asthma| climate| outdoor no2 pollution| traffic-related pollution|respiratory health survey| diesel exhaust particles| long-term exposure| air-pollution| childhood asthma| lung-function| indoor allergens| new-zealand| symptoms| pollutants.	OCT-2002	allergic rhinitis| asthma| climate| outdoor no2 pollution| traffic-related pollution|respiratory health survey| diesel exhaust particles| long-term exposure| air-pollution| childhood asthma| lung-function| indoor allergens| new-zealand| symptoms| pollutants	de Marco, R; Poli, A; Ferrari, M; Accordini, S; Giammanco, G; Bugiani, M; Villani, S; Ponzio, M; Bono, R; Carrozzi, L; Cavallini, R; Cazzoletti, L; Dallari, R; Ginesu, F; Lauriola, P; Mandrioli, P; Perfetti, L; Pignato, S; Pirina, P; Struzzo, P	The impact of climate and traffic-related NO2 on the prevalence of asthma and allergic rhinitis in Italy		CLINICAL AND EXPERIMENTAL ALLERGY	allergic rhinitis; asthma; climate; outdoor NO2 pollution; traffic-related pollution	RESPIRATORY HEALTH SURVEY; DIESEL EXHAUST PARTICLES; LONG-TERM EXPOSURE; AIR-POLLUTION; CHILDHOOD ASTHMA; LUNG-FUNCTION; INDOOR ALLERGENS; NEW-ZEALAND; SYMPTOMS; POLLUTANTS	Background Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies. Aim To evaluate to what extent climate and outdoor NO2 pollution can explain the geographical variation in the prevalence of asthma and allergic rhinitis, and to estimate the relative risk for exposure to different levels of these two factors. Methods The impact of climate and long-term exposure to nitrogen dioxide (NO2) pollution on asthma and allergic rhinitis was assessed in a cross-sectional study, carried out during 1998 to 2000 on young adults aged 20 to 44 years (n = 18 873), living in 13 areas from two different Italian climatic regions (subcontinental and Mediterranean). Results Mediterranean areas had a significantly higher prevalence of asthma-like symptoms (P < 0.001), higher annual mean temperature (16.2 degreesC vs. 12.9 degreesC), lower temperature range (16.0 Cdegrees vs. 22.1 Cdegrees) and lower NO2 levels (31.46 mug/m(3) vs. 57.99 mug/m(3)) than subcontinental ones. Mediterranean climate was associated with an increased risk of wheeze (OR = 1.23; 95% CI 1.13 to 1.35), tightness in the chest (OR = 1.21; 95% CI 1.11 to 1.33), shortness of breath (OR = 1.21; 95% CI 1.08 to 1.36) and asthma attacks (OR = 1.19; 95% CI 1.07 to 1.31). After adjusting for climate, an increase of 18.3 mug/m(3) in NO2 levels moderately increased the risk of asthma attacks (OR = 1.13; 95% CI 0.98 to 1.32), tightness in the chest (OR = 1.11; 95% CI 0.98 to 1.26) and wheeze (OR = 1.11; 95% CI 0.96 to 1.28). When the levels of outdoor NO2 exposure rose, the prevalence of allergic rhinitis increased significantly in the Mediterranean region (OR = 1.38; 95% CI 1.12 to 1.69), but not in the subcontinental one (OR = 1.03; 95% CI 0.83 to 1.28). Conclusion Our results show that the prevalence of asthma increases when annual mean temperature increases and temperature range decreases. Furthermore, climate interacts with NO2 outdoor exposure, increasing the risk for allergic rhinitis in people exposed to high stable temperatures. A long-term role for the effect of traffic pollution on asthma is also suggested.	49	72	2002	8	10.1046/j.1365-2745.2002.01466.x	Allergy; Immunology
The role of indoor allergen sensitization and exposure in causing morbidity in women with asthma. Longitudinal evidence that indoor allergen exposure causes morbidity in sensitized individuals with asthma is scarce. We evaluated the association of allergen sensitization and home exposure to short and long-term morbidity in 140 women with asthma and to asthma prevalence in 458 women from metropolitan Boston. Cockroach (Blattella germanica), dust mite (Dermatophagoides farinae), and cat (Felis domesticus) allergens in home dust samples, and specific immunoglobulln E antibodies were measured at outset, and doctor-diagnosed asthma and markers of asthma morbidity were ascertained by questionnaire during a 4-year follow-up. Cat- and cockroach-sensitive (immunoglobulin E immunocap [Cap] class greater than or equal to 1) women with asthma reported greater morbidity in the past year at the start, and during follow-up, if high levels of the relevant allergen were found. Women with asthma sensitized to cat allergen and with concentrations at 8 mug/g or greater were more likely to have used steroid (adjusted odds ratio [95% confidence interval] 2.7 [1.2-6.2]) and wheezed without a cold (odds ratio 6.8 [3.314.0]) during follow-up. Those sensitized and exposed to cockroach (Bla g I or 2 greater than or equal to 2 U/g) were at least three times more likely to have used steroid and to have attended a hospital emergency room; the size of the effect upon steroid use was maintained, but the precision was reduced and the 95% confidence interval included one (p = 0.07), with adjustment for race and poverty. We conclude that cockroach and cat allergens may contribute to asthma morbidity in sensitized women.. home allergens| cockroach| cat| sensitization| asthma morbidity|inner-city children| risk-factors| cockroach allergen| determinants| eosinophilia| predictors| avoidance| antigen| homes| area.	APR 1-2002	home allergens| cockroach| cat| sensitization| asthma morbidity|inner-city children| risk-factors| cockroach allergen| determinants| eosinophilia| predictors| avoidance| antigen| homes| area	Lewis, SA; Weiss, ST; Platts-Mills, TAE; Burge, H; Gold, DR	The role of indoor allergen sensitization and exposure in causing morbidity in women with asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	home allergens; cockroach; cat; sensitization; asthma morbidity	INNER-CITY CHILDREN; RISK-FACTORS; COCKROACH ALLERGEN; DETERMINANTS; EOSINOPHILIA; PREDICTORS; AVOIDANCE; ANTIGEN; HOMES; AREA	Longitudinal evidence that indoor allergen exposure causes morbidity in sensitized individuals with asthma is scarce. We evaluated the association of allergen sensitization and home exposure to short and long-term morbidity in 140 women with asthma and to asthma prevalence in 458 women from metropolitan Boston. Cockroach (Blattella germanica), dust mite (Dermatophagoides farinae), and cat (Felis domesticus) allergens in home dust samples, and specific immunoglobulln E antibodies were measured at outset, and doctor-diagnosed asthma and markers of asthma morbidity were ascertained by questionnaire during a 4-year follow-up. Cat- and cockroach-sensitive (immunoglobulin E immunocap [Cap] class greater than or equal to 1) women with asthma reported greater morbidity in the past year at the start, and during follow-up, if high levels of the relevant allergen were found. Women with asthma sensitized to cat allergen and with concentrations at 8 mug/g or greater were more likely to have used steroid (adjusted odds ratio [95% confidence interval] 2.7 [1.2-6.2]) and wheezed without a cold (odds ratio 6.8 [3.314.0]) during follow-up. Those sensitized and exposed to cockroach (Bla g I or 2 greater than or equal to 2 U/g) were at least three times more likely to have used steroid and to have attended a hospital emergency room; the size of the effect upon steroid use was maintained, but the precision was reduced and the 95% confidence interval included one (p = 0.07), with adjustment for race and poverty. We conclude that cockroach and cat allergens may contribute to asthma morbidity in sensitized women.	23	72	2002	6	10.1164/rccm.2103044	General & Internal Medicine; Respiratory System
Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants. Background: Despite having a work related deterioration in peak expiratory flow (PEF), many workers with occupational asthma show a low degree of within day diurnal variability atypical of non-occupational asthma. It was hypothesised that these workers would have a neutrophilic rather than an eosinophilic airway inflammatory response. Methods: Thirty eight consecutive workers with occupational asthma induced by low molecular weight agents underwent sputum induction and assessment of airway physiology while still exposed at work. Results: Only 14 (36.8%) of the 38 workers had sputum eosinophilia (>2.2%). Both eosinophilic and non-eosinophilic groups had sputum neutrophilia (mean (SD) 59.5 (19.6)% and 55.1 (18.8)%, respectively). The diurnal variation and magnitude of fall in PEF during work periods was not significantly different between workers with and without sputum eosinophilia. Those with eosinophilia had a lower forced expiratory volume in 1 second (FEV1; 61.4% v 83% predicted, mean difference 21.6, 95% confidence interval (CI) 9.2 to 34.1 p=0.001) and greater methacholine reactivity (geometric mean PD20 253 mug v 1401 mug, p=0.007), hey also had greater bronchodilator reversibility (397 ml v 161 ml, mean difference 236, 95% Cl of difference 84 to 389, p=0.003) which was unrelated to differences in baseline FEV1. The presence of sputum eosinophilia did not relate to the causative agent, duration of exposure, atopy, or lack of treatment. Conclusions: Asthma caused by low molecular weight agents can be separated into eosinophilic and non-eosinophilic pathophysiological variants with the latter predominating. Both groups had evidence of sputum neutrophilia. Sputum eosinophilia was associated with more severe disease and greater bronchodilator reversibility but no difference in PEF response to work exposure.. exhaled nitric-oxide| red cedar asthma| induced sputum| airway inflammation| bronchial responsiveness| flow-rate| diagnosis| severity| counts.	MAR-2002	exhaled nitric-oxide| red cedar asthma| induced sputum| airway inflammation| bronchial responsiveness| flow-rate| diagnosis| severity| counts	Anees, W; Huggins, V; Pavord, ID; Robertson, AS; Burge, PS	Occupational asthma due to low molecular weight agents: eosinophilic and non-eosinophilic variants		THORAX		EXHALED NITRIC-OXIDE; RED CEDAR ASTHMA; INDUCED SPUTUM; AIRWAY INFLAMMATION; BRONCHIAL RESPONSIVENESS; FLOW-RATE; DIAGNOSIS; SEVERITY; COUNTS	Background: Despite having a work related deterioration in peak expiratory flow (PEF), many workers with occupational asthma show a low degree of within day diurnal variability atypical of non-occupational asthma. It was hypothesised that these workers would have a neutrophilic rather than an eosinophilic airway inflammatory response. Methods: Thirty eight consecutive workers with occupational asthma induced by low molecular weight agents underwent sputum induction and assessment of airway physiology while still exposed at work. Results: Only 14 (36.8%) of the 38 workers had sputum eosinophilia (>2.2%). Both eosinophilic and non-eosinophilic groups had sputum neutrophilia (mean (SD) 59.5 (19.6)% and 55.1 (18.8)%, respectively). The diurnal variation and magnitude of fall in PEF during work periods was not significantly different between workers with and without sputum eosinophilia. Those with eosinophilia had a lower forced expiratory volume in 1 second (FEV1; 61.4% v 83% predicted, mean difference 21.6, 95% confidence interval (CI) 9.2 to 34.1 p=0.001) and greater methacholine reactivity (geometric mean PD20 253 mug v 1401 mug, p=0.007), hey also had greater bronchodilator reversibility (397 ml v 161 ml, mean difference 236, 95% Cl of difference 84 to 389, p=0.003) which was unrelated to differences in baseline FEV1. The presence of sputum eosinophilia did not relate to the causative agent, duration of exposure, atopy, or lack of treatment. Conclusions: Asthma caused by low molecular weight agents can be separated into eosinophilic and non-eosinophilic pathophysiological variants with the latter predominating. Both groups had evidence of sputum neutrophilia. Sputum eosinophilia was associated with more severe disease and greater bronchodilator reversibility but no difference in PEF response to work exposure.	24	72	2002	6	10.1136/thorax.57.3.231	Respiratory System
Asthma symptoms, morbidity, and antiinflammatory use in inner-city children. Background. Asthma is a major cause of morbidity that disproportionately affects inner-city children. For children with persistent asthma, defined as having asthma symptoms 3 or more days per week or 3 or more nights per month, national guidelines recommend the use of daily antiinflammatory agents. Despite these recommendations, antiinflammatory agents remain underused, particularly in inner-city children with high asthma morbidity. Objectives. The objectives of our study were to determine: 1) whether persistent asthma symptoms in inner-city children are related to acute care utilization and to the frequency of acute exacerbations; 2) whether children with persistent asthma are receiving recommended daily antiinflammatory agents; and 3) whether antiinflammatory medication use relates to sociodemographic factors, caretaker self-efficacy, the frequency of primary care visits, and/or measures of quality asthma care. Design and Methods. A 64-item telephone survey was administered between July 1996 and June 1997 to 219 parental caretakers of 2- to 12-year-old children who had been hospitalized with asthma at an inner-city medical center between January 1995 and February 1996. Persistent asthma symptoms were assessed by inquiring about the frequency of daily and nocturnal asthma symptoms over the last 4 weeks. Children's asthma severity was classified by applying the 1997 National Asthma Education and Prevention Program (NAEPP) Asthma Guidelines' severity classification scheme based on the frequency of asthma symptoms. Asthma morbidity was defined as the frequency of acute asthma exacerbations, emergency department visits and hospitalizations. Daily antiinflammatory medication use was compared by sociodemographic factors, caretaker self-efficacy, frequency of primary care visits, and measures of quality asthma home management. Results. In this sample, quantifying persistent asthma symptoms and applying the NAEPP symptom criteria identified 17% of the children with mild intermittent asthma, 27% with mild persistent asthma and 56% with moderate to severe persistent asthma. There were no differences in the age of the children in the 3 groups (mean age: 6 years). Asthma morbidity, as measured by the number of asthma exacerbations in the last 6 months, was significantly higher in the children with moderate to severe persistent asthma compared with children with mild intermittent asthma (9.8 vs 3.5) or mild persistent asthma (9.8 vs 4.5). In addition, there were significantly more emergency department visits in the moderate to severe group than in the mild persistent (3.05 vs 1.69) or mild intermittent group (3.05 vs 1.76). Lastly, as asthma symptom frequency increased, there were trends toward more hospitalizations and more days hospitalized. Overall, 35% of the 219 families reported giving daily antiinflammatory medications to their child (mostly cromolyn sodium). Of the 181 children (83%) who met NA-EPP symptom criteria for persistent asthma, only 39% were receiving daily antiinflammatory treatment. Of the children with symptoms of moderate to severe asthma, only 15% were receiving inhaled steroids in contrast to the guidelines' recommendations. Use of antiinflammatory agents was not related to caretaker sociodemographic factors or self-efficacy scores. Measures of quality asthma home management, which included use of mattress covers, written plans, and peak flow meters, correlated positively with use of antiinflammatory agents. Children whose families reported using daily antiinflammatory medications had more primary care visits in the last 6 months than those children not receiving antiinflammatory medications. Conclusion. Questioning parents about the frequency of their child's asthma symptoms is an important, inexpensive, and readily accessible bedside and office tool that may aid in the detection of persistent symptoms and help direct therapy. Our study suggests that classifying asthma severity by quantifying persistent asthma symptoms, as defined in the NAEPP Guidelines, is a clinically useful tool that relates to asthma morbidity. In our sample of previously hospitalized children with asthma, 83% met 1997 NAEPP symptom criteria for persistent asthma, and yet only 35% were receiving daily antiinflammatory agents. Use of antiinflammatory agents correlated positively with other indicators of quality asthma home management. Additional work is necessary to increase appropriate use of antiinflammatory agents in this population, and in particular, to increase inhaled steroid use for children with moderate or severe symptoms.. inner-city children| asthma severity| persistent asthma| guidelines| morbidity| antiinflammatory therapy| inhaled steroids| symptom days|airway inflammation| pulmonary-function| lung-function| severity.	AUG-2001	inner-city children| asthma severity| persistent asthma| guidelines| morbidity| antiinflammatory therapy| inhaled steroids| symptom days|airway inflammation| pulmonary-function| lung-function| severity	Warman, KL; Silver, EJ; Stein, REK	Asthma symptoms, morbidity, and antiinflammatory use in inner-city children		PEDIATRICS	inner-city children; asthma severity; persistent asthma; guidelines; morbidity; antiinflammatory therapy; inhaled steroids; symptom days	AIRWAY INFLAMMATION; PULMONARY-FUNCTION; LUNG-FUNCTION; SEVERITY	Background. Asthma is a major cause of morbidity that disproportionately affects inner-city children. For children with persistent asthma, defined as having asthma symptoms 3 or more days per week or 3 or more nights per month, national guidelines recommend the use of daily antiinflammatory agents. Despite these recommendations, antiinflammatory agents remain underused, particularly in inner-city children with high asthma morbidity. Objectives. The objectives of our study were to determine: 1) whether persistent asthma symptoms in inner-city children are related to acute care utilization and to the frequency of acute exacerbations; 2) whether children with persistent asthma are receiving recommended daily antiinflammatory agents; and 3) whether antiinflammatory medication use relates to sociodemographic factors, caretaker self-efficacy, the frequency of primary care visits, and/or measures of quality asthma care. Design and Methods. A 64-item telephone survey was administered between July 1996 and June 1997 to 219 parental caretakers of 2- to 12-year-old children who had been hospitalized with asthma at an inner-city medical center between January 1995 and February 1996. Persistent asthma symptoms were assessed by inquiring about the frequency of daily and nocturnal asthma symptoms over the last 4 weeks. Children's asthma severity was classified by applying the 1997 National Asthma Education and Prevention Program (NAEPP) Asthma Guidelines' severity classification scheme based on the frequency of asthma symptoms. Asthma morbidity was defined as the frequency of acute asthma exacerbations, emergency department visits and hospitalizations. Daily antiinflammatory medication use was compared by sociodemographic factors, caretaker self-efficacy, frequency of primary care visits, and measures of quality asthma home management. Results. In this sample, quantifying persistent asthma symptoms and applying the NAEPP symptom criteria identified 17% of the children with mild intermittent asthma, 27% with mild persistent asthma and 56% with moderate to severe persistent asthma. There were no differences in the age of the children in the 3 groups (mean age: 6 years). Asthma morbidity, as measured by the number of asthma exacerbations in the last 6 months, was significantly higher in the children with moderate to severe persistent asthma compared with children with mild intermittent asthma (9.8 vs 3.5) or mild persistent asthma (9.8 vs 4.5). In addition, there were significantly more emergency department visits in the moderate to severe group than in the mild persistent (3.05 vs 1.69) or mild intermittent group (3.05 vs 1.76). Lastly, as asthma symptom frequency increased, there were trends toward more hospitalizations and more days hospitalized. Overall, 35% of the 219 families reported giving daily antiinflammatory medications to their child (mostly cromolyn sodium). Of the 181 children (83%) who met NA-EPP symptom criteria for persistent asthma, only 39% were receiving daily antiinflammatory treatment. Of the children with symptoms of moderate to severe asthma, only 15% were receiving inhaled steroids in contrast to the guidelines' recommendations. Use of antiinflammatory agents was not related to caretaker sociodemographic factors or self-efficacy scores. Measures of quality asthma home management, which included use of mattress covers, written plans, and peak flow meters, correlated positively with use of antiinflammatory agents. Children whose families reported using daily antiinflammatory medications had more primary care visits in the last 6 months than those children not receiving antiinflammatory medications. Conclusion. Questioning parents about the frequency of their child's asthma symptoms is an important, inexpensive, and readily accessible bedside and office tool that may aid in the detection of persistent symptoms and help direct therapy. Our study suggests that classifying asthma severity by quantifying persistent asthma symptoms, as defined in the NAEPP Guidelines, is a clinically useful tool that relates to asthma morbidity. In our sample of previously hospitalized children with asthma, 83% met 1997 NAEPP symptom criteria for persistent asthma, and yet only 35% were receiving daily antiinflammatory agents. Use of antiinflammatory agents correlated positively with other indicators of quality asthma home management. Additional work is necessary to increase appropriate use of antiinflammatory agents in this population, and in particular, to increase inhaled steroid use for children with moderate or severe symptoms.	20	72	2001	6	10.1542/peds.108.2.277	Pediatrics
Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitis. Background Avoidance of allergens has been shown to be of benefit in patients with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is so far little information about the effect of house dust mite elimination strategies. Objectives We therefore performed a randomized controlled study of house dust mite control in patients with this disease. Methods Twenty adult patients with moderate to severe atopic dermatitis were included. Inclusion criteria were a positive RAST to house dust mite antigen (CAP class > 3) and a concentration of > 2 mug g(-1) of the house dust mite antigen Der p1 in the patient's mattress dust. Patients were randomized to either the active treatment group (allergen-impermeable mattress encasing, acaricide spray containing tannic acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray containing water and traces of ethanol). Severity of disease was estimated every 2 months by an established score (SCORAD), and eosinophil cationic protein (ECP) in the serum was determined by enzyme-linked immunosorbent assay. Furthermore, the use of topical steroids was quantified. Patients assessed daytime pruritus and pruritus-induced sleeplessness weekly on a visual analogue scale. The study lasted 1 year. Results At the end of the study, the active treatment group showed a statistically significant reduction in Der p1 exposure as compared with the control group. However, when comparing the change from the start to the end of the study, there was no statistically significant difference between active treatment and control groups as measured by the SCORAD score and by ECP levels in the serum. Some patients in the active treatment group reported less pruritus-induced sleeplessness, but there was no statistically significant difference between the two treatment groups. Conclusions For adult patients with atopic dermatitis it was shown that 1 year of house dust mite avoidance reduced the allergen exposure, but an improvement of overall disease activity was not demonstrated.. acaricides| atopic dermatitis| clinical trial| house dust mite| mattress encasing|patch test| allergen avoidance| controlled trial| exposure| asthma| eczema.	JUL-2001	acaricides| atopic dermatitis| clinical trial| house dust mite| mattress encasing|patch test| allergen avoidance| controlled trial| exposure| asthma| eczema	Gutgesell, C; Heise, S; Seubert, S; Seubert, A; Domhof, S; Brunner, E; Neumann, C	Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitis		BRITISH JOURNAL OF DERMATOLOGY	acaricides; atopic dermatitis; clinical trial; house dust mite; mattress encasing	PATCH TEST; ALLERGEN AVOIDANCE; CONTROLLED TRIAL; EXPOSURE; ASTHMA; ECZEMA	Background Avoidance of allergens has been shown to be of benefit in patients with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is so far little information about the effect of house dust mite elimination strategies. Objectives We therefore performed a randomized controlled study of house dust mite control in patients with this disease. Methods Twenty adult patients with moderate to severe atopic dermatitis were included. Inclusion criteria were a positive RAST to house dust mite antigen (CAP class > 3) and a concentration of > 2 mug g(-1) of the house dust mite antigen Der p1 in the patient's mattress dust. Patients were randomized to either the active treatment group (allergen-impermeable mattress encasing, acaricide spray containing tannic acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray containing water and traces of ethanol). Severity of disease was estimated every 2 months by an established score (SCORAD), and eosinophil cationic protein (ECP) in the serum was determined by enzyme-linked immunosorbent assay. Furthermore, the use of topical steroids was quantified. Patients assessed daytime pruritus and pruritus-induced sleeplessness weekly on a visual analogue scale. The study lasted 1 year. Results At the end of the study, the active treatment group showed a statistically significant reduction in Der p1 exposure as compared with the control group. However, when comparing the change from the start to the end of the study, there was no statistically significant difference between active treatment and control groups as measured by the SCORAD score and by ECP levels in the serum. Some patients in the active treatment group reported less pruritus-induced sleeplessness, but there was no statistically significant difference between the two treatment groups. Conclusions For adult patients with atopic dermatitis it was shown that 1 year of house dust mite avoidance reduced the allergen exposure, but an improvement of overall disease activity was not demonstrated.	18	72	2001	5	10.1046/j.1365-2133.2001.04283.x	Dermatology
Murine model of atopic dermatitis associated with food hypersensitivity. Background: Atopic dermatitis (AD) is an eczematous skin eruption that generally begins in early infancy and affects up to 126 of the population. The cause of this disorder is not fully understood, although it is frequently the first sign of atopic disease and is characterized by an elevated serum IgE level, eosinophilia, and histologic tissue changes characterized early by spongiosis and a CD4(+) T(H)2 cellular infiltrate. Hypersensitivity to foods has been implicated as one causative factor in up to 40% of children with moderate-to-severe AD. Objective: The purpose of this study was to establish a murine model of food-induced AD. Methods: Female C3H/HeJ mice were sensitized orally to cow's milk or peanut with a cholera toxin adjuvant and then subjected to low-grade allergen exposure. Histologic examination of skin lesions, allergen-specific serum Ig levels, and allergen-induced T-cell proliferation and cytokine production were examined. Results: An eczematous eruption developed in approximately one third of mice after low-grade exposure to milk or peanut proteins. Peripheral blood eosinophilia and elevated serum IgE levels were noted. Histologic examination of the Lesional skin revealed spongiosis and a cellular infiltrate consisting of CD4(+) lymphocytes, eosinophils, and mast cells, IL-5 and IL-13 mRNA expression was elevated only in the skin of mice with the eczematous eruption. Treatment of the eruption with topical corticosteroids led to decreased pruritus and resolution of the cutaneous eruption. Conclusion: This eczematous eruption resembles AD in human subjects and should provide a useful model for studying immunopathogenic mechanisms of food hypersensitivity in AD.. atopic dermatitis| eczema| food hypersensitivity| murine model| t(h)2-like cytokines| ige-mediated hypersensitivity|polymerase chain-reaction| alopecia-areata| t-cells| intestinal permeability| allergic dermatitis| ige hyperproduction| aerosolized antigen| messenger-rna| c3h/hej mice| nc/nga mice.	APR-2001	atopic dermatitis| eczema| food hypersensitivity| murine model| t(h)2-like cytokines| ige-mediated hypersensitivity|polymerase chain-reaction| alopecia-areata| t-cells| intestinal permeability| allergic dermatitis| ige hyperproduction| aerosolized antigen| messenger-rna| c3h/hej mice| nc/nga mice	Li, XM; Kleiner, G; Huang, CK; Lee, SY; Schofield, B; Soter, NA; Sampson, HA	Murine model of atopic dermatitis associated with food hypersensitivity		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopic dermatitis; eczema; food hypersensitivity; murine model; T(H)2-like cytokines; IgE-mediated hypersensitivity	POLYMERASE CHAIN-REACTION; ALOPECIA-AREATA; T-CELLS; INTESTINAL PERMEABILITY; ALLERGIC DERMATITIS; IGE HYPERPRODUCTION; AEROSOLIZED ANTIGEN; MESSENGER-RNA; C3H/HEJ MICE; NC/NGA MICE	Background: Atopic dermatitis (AD) is an eczematous skin eruption that generally begins in early infancy and affects up to 126 of the population. The cause of this disorder is not fully understood, although it is frequently the first sign of atopic disease and is characterized by an elevated serum IgE level, eosinophilia, and histologic tissue changes characterized early by spongiosis and a CD4(+) T(H)2 cellular infiltrate. Hypersensitivity to foods has been implicated as one causative factor in up to 40% of children with moderate-to-severe AD. Objective: The purpose of this study was to establish a murine model of food-induced AD. Methods: Female C3H/HeJ mice were sensitized orally to cow's milk or peanut with a cholera toxin adjuvant and then subjected to low-grade allergen exposure. Histologic examination of skin lesions, allergen-specific serum Ig levels, and allergen-induced T-cell proliferation and cytokine production were examined. Results: An eczematous eruption developed in approximately one third of mice after low-grade exposure to milk or peanut proteins. Peripheral blood eosinophilia and elevated serum IgE levels were noted. Histologic examination of the Lesional skin revealed spongiosis and a cellular infiltrate consisting of CD4(+) lymphocytes, eosinophils, and mast cells, IL-5 and IL-13 mRNA expression was elevated only in the skin of mice with the eczematous eruption. Treatment of the eruption with topical corticosteroids led to decreased pruritus and resolution of the cutaneous eruption. Conclusion: This eczematous eruption resembles AD in human subjects and should provide a useful model for studying immunopathogenic mechanisms of food hypersensitivity in AD.	53	72	2001	10	10.1067/mai.2001.114110	Allergy; Immunology
"Adult-onset asthma is associated with self-reported mold or environmental tobacco smoke exposures in the home. Background: In recent years, we have gained better knowledge about the influence of indoor environments on respiratory symptoms and asthma. The purpose of this study was to examine certain exposures in the home environment and the risk of adult-onset asthma. Methods: A nested case-referent study of adult-onset asthma was performed in a random population sample (n = 15 813), aged 20-50 years. Cases for the study included subjects reporting ""physician-diagnosed"" asthma (n = 174). The referents (n = 870) were randomly selected from the whole population sample. The case-referent sample was investigated with a comprehensive mailed questionnaire about exposures in the home environment, asthma, respiratory symptoms, smoking habits, and atopy. Odds ratios (OR) with 95% confidence intervals (CI) were calculated while controlling for age, sex, smoking, and atopy. Results: Increased adjusted OR for asthma were associated with exposure to molds (OR 2.2, 95% CI 1.4-3.5), environmental tobacco smoke (OR 2.4, 95% CI 1.4-4.1), and the presence of a wood stove (OR 1.7, 95% CI 1.2-2.5). Conclusions: This population-based case-referent study indicates that self-reported domestic exposures to molds or environmental tobacco smoke can be associated with adult-onset asthma.. asthma| epidemiology| home environment| questionnaire|risk-factors| occupational exposures| respiratory symptoms| childhood asthma| bronchial hyperreactivity| health| dampness| children| population."	APR-2001	asthma| epidemiology| home environment| questionnaire|risk-factors| occupational exposures| respiratory symptoms| childhood asthma| bronchial hyperreactivity| health| dampness| children| population	Thorn, J; Brisman, J; Toren, K	Adult-onset asthma is associated with self-reported mold or environmental tobacco smoke exposures in the home		ALLERGY	asthma; epidemiology; home environment; questionnaire	RISK-FACTORS; OCCUPATIONAL EXPOSURES; RESPIRATORY SYMPTOMS; CHILDHOOD ASTHMA; BRONCHIAL HYPERREACTIVITY; HEALTH; DAMPNESS; CHILDREN; POPULATION	"Background: In recent years, we have gained better knowledge about the influence of indoor environments on respiratory symptoms and asthma. The purpose of this study was to examine certain exposures in the home environment and the risk of adult-onset asthma. Methods: A nested case-referent study of adult-onset asthma was performed in a random population sample (n = 15 813), aged 20-50 years. Cases for the study included subjects reporting ""physician-diagnosed"" asthma (n = 174). The referents (n = 870) were randomly selected from the whole population sample. The case-referent sample was investigated with a comprehensive mailed questionnaire about exposures in the home environment, asthma, respiratory symptoms, smoking habits, and atopy. Odds ratios (OR) with 95% confidence intervals (CI) were calculated while controlling for age, sex, smoking, and atopy. Results: Increased adjusted OR for asthma were associated with exposure to molds (OR 2.2, 95% CI 1.4-3.5), environmental tobacco smoke (OR 2.4, 95% CI 1.4-4.1), and the presence of a wood stove (OR 1.7, 95% CI 1.2-2.5). Conclusions: This population-based case-referent study indicates that self-reported domestic exposures to molds or environmental tobacco smoke can be associated with adult-onset asthma."	27	72	2001	6	10.1034/j.1398-9995.2001.00805.x	Allergy; Immunology
Spore germination increases allergen release from Alternaria. Allergen released from individual spores of the fungus Alternaria has not been investigated. Germination of spores has been suggested to increase allergen release. This study examined allergen released from individual spores and the effect of germination on allergen availability. Allergen release was determined with the Halogen (Inhalix, Sydney, Australia) immunoassay, by use of serum IgE from Alternaria-sensitized subjects and 3 Alt a 1-specific antibodies. Not all spores released allergen. Germination of the spores significantly increased the proportion that released allergen (P < .0001 for all antibodies). Alt a 1 may be a minor contributor to the total allergen released from spores except when spores have germinated. How these results reflect the allergen content of spores in the air that we breathe requires investigation.. allergen| alt a 1| alternaria| germination| halogen| immunoassay|aspergillus-fumigatus.	FEB-2001	allergen| alt a 1| alternaria| germination| halogen| immunoassay|aspergillus-fumigatus	Mitakakis, TZ; Barnes, C; Tovey, ER	Spore germination increases allergen release from Alternaria		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen; Alt a 1; Alternaria; germination; Halogen; immunoassay	ASPERGILLUS-FUMIGATUS	Allergen released from individual spores of the fungus Alternaria has not been investigated. Germination of spores has been suggested to increase allergen release. This study examined allergen released from individual spores and the effect of germination on allergen availability. Allergen release was determined with the Halogen (Inhalix, Sydney, Australia) immunoassay, by use of serum IgE from Alternaria-sensitized subjects and 3 Alt a 1-specific antibodies. Not all spores released allergen. Germination of the spores significantly increased the proportion that released allergen (P < .0001 for all antibodies). Alt a 1 may be a minor contributor to the total allergen released from spores except when spores have germinated. How these results reflect the allergen content of spores in the air that we breathe requires investigation.	9	72	2001	3	10.1067/mai.2001.112602	Allergy; Immunology
Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae). To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus mon keys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA, During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance,which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys, After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys, Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes, Intrapulmonary bronchi of sensitized monkeys had focal mucus tell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone, We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.. lymphocyte-t activation| antigen challenge| mediator release| macaca-mulatta| airway| histamine| prostaglandins| primates| disease| cells.	JAN-2001	lymphocyte-t activation| antigen challenge| mediator release| macaca-mulatta| airway| histamine| prostaglandins| primates| disease| cells	Schelegle, ES; Gershwin, LJ; Miller, LA; Fanucchi, MV; Van Winkle, LS; Gerriets, JP; Walby, WF; Omlor, AM; Buckpitt, AR; Tarkington, BK; Wong, VJ; Joad, JP; Pinkerton, KB; Wu, R; Evans, MJ; Hyde, DM; Plopper, CG	Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae)		AMERICAN JOURNAL OF PATHOLOGY		LYMPHOCYTE-T ACTIVATION; ANTIGEN CHALLENGE; MEDIATOR RELEASE; MACACA-MULATTA; AIRWAY; HISTAMINE; PROSTAGLANDINS; PRIMATES; DISEASE; CELLS	To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus mon keys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA, During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance,which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys, After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys, Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes, Intrapulmonary bronchi of sensitized monkeys had focal mucus tell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone, We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.	32	72	2001	9	10.1016/S0002-9440(10)63973-9	Pathology
Differences between the sexes with regard to work-related skin disease. Work-related skin disease is common and usually presents as hand eczema. From the Occupational Injury Information System in Sweden, as well as from registers of industrial injuries in other countries, it is evident that females report skin disease more often than males. Epidemiological studies of hand eczema also show that women are more often affected than men, in particular young women. The most common type of hand eczema is irritant contact dermatitis, which is often caused by wet work. Many female-dominated occupations involve extensive wet work, e.g., hairdressing, catering, cleaning and health-care work. These occupations are also high-risk occupations for hand eczema. Experimental studies of skin irritation have not confirmed differences between the sexes; thus, the higher prevalence of irritant contact dermatitis among females is most likely due to exposure, occupational and non-occupational. Nickel allergy is the most common contact allergy, which is most frequent in young females, and in 30-40% results over time in hand eczema. Hand eczema has an impact on quality of life and females seem to report a higher degree of discomfort than males. To achieve the optimal effect of preventive efforts regarding occupational skin disease, the focus for prevention should aim at reducing wet exposure.. females| differences between the sexes| hand eczema| high-risk occupation| males| occupational skin disease| prevalence| prevention| risk factor| wet work|hand dermatitis| allergenic activity| eczema| hairdressers| surfactants| occupation| population| oxidation| bakers| atopy.	AUG-2000	females| differences between the sexes| hand eczema| high-risk occupation| males| occupational skin disease| prevalence| prevention| risk factor| wet work|hand dermatitis| allergenic activity| eczema| hairdressers| surfactants| occupation| population| oxidation| bakers| atopy	Meding, B	Differences between the sexes with regard to work-related skin disease		CONTACT DERMATITIS	females; differences between the sexes; hand eczema; high-risk occupation; males; occupational skin disease; prevalence; prevention; risk factor; wet work	HAND DERMATITIS; ALLERGENIC ACTIVITY; ECZEMA; HAIRDRESSERS; SURFACTANTS; OCCUPATION; POPULATION; OXIDATION; BAKERS; ATOPY	Work-related skin disease is common and usually presents as hand eczema. From the Occupational Injury Information System in Sweden, as well as from registers of industrial injuries in other countries, it is evident that females report skin disease more often than males. Epidemiological studies of hand eczema also show that women are more often affected than men, in particular young women. The most common type of hand eczema is irritant contact dermatitis, which is often caused by wet work. Many female-dominated occupations involve extensive wet work, e.g., hairdressing, catering, cleaning and health-care work. These occupations are also high-risk occupations for hand eczema. Experimental studies of skin irritation have not confirmed differences between the sexes; thus, the higher prevalence of irritant contact dermatitis among females is most likely due to exposure, occupational and non-occupational. Nickel allergy is the most common contact allergy, which is most frequent in young females, and in 30-40% results over time in hand eczema. Hand eczema has an impact on quality of life and females seem to report a higher degree of discomfort than males. To achieve the optimal effect of preventive efforts regarding occupational skin disease, the focus for prevention should aim at reducing wet exposure.	39	72	2000	7	10.1034/j.1600-0536.2000.043002065.x	Allergy; Dermatology
Absence of relationship between tuberculin reactivity and atopy in BCG vaccinated young adults. Background-An inverse association between tuberculin responses and atopy has been observed in Japanese children, indicating that BCG immunisation, subclinical exposure to Mycobacterium tuberculosis without clinical disease, or host characteristics may influence the T helper (Th) lymphocyte balance with decreased atopy as a result. This study was undertaken to determine whether tuberculin reactivity is inversely related to atopy in young adults vaccinated with BCG at the age of 14. Methods-Men and women aged 20-44 years were tested using the adrenaline-Pirquet test with Norwegian produced synthetic medium tuberculin (n = 891). In addition, their serum total and specific IgE antibodies against mite, cat, timothy grass, mould and birch were measured. Results-Of the 574 subjects with complete examinations, 64% had a positive adrenaline-Pirquet tuberculin test (greater than or equal to 4 mm) and 27% exhibited IgE antibodies (greater than or equal to 0.35 kU/l) to one or more of the five specific allergens. The geometric mean of total serum IgE in the population was 30.2 kU/l. Tuberculin reactivity and log IgE were not correlated (r = 0.043, p 0.30). The mean tuberculin reactivity was 4.6 mm, 4.9 mm, and 5.0 mm in the lower, middle and upper tertile of IgE distribution (< 14 kU/l, 14-61 kU/l, > 61 kU/l). The prevalence of atopy, as assessed by either the presence of any of the five specific IgE antibodies or by each specific IgE antibody separately, did not differ between subjects with a positive and those with a negative tuberculin test. These results persisted after adjustment for age, sex, and smoking status in multivariate logistic regression analyses. Conclusions-In this young adult population, BCG vaccinated at the age of 14, no significant relationship between a positive tuberculin reaction and atopy was observed. If a true relationship had been found, our study suggests that it may be limited to populations immunised in early childhood when a substantial modulation of the immune system can occur.. atopy| asthma| tuberculosis| immunisation| bcg vaccination|infection| responses| disorder| children.	JUN-2000	atopy| asthma| tuberculosis| immunisation| bcg vaccination|infection| responses| disorder| children	Omenaas, E; Jentoft, HF; Vollmer, WM; Buist, AS; Gulsvik, A	Absence of relationship between tuberculin reactivity and atopy in BCG vaccinated young adults		THORAX	atopy; asthma; tuberculosis; immunisation; BCG vaccination	INFECTION; RESPONSES; DISORDER; CHILDREN	Background-An inverse association between tuberculin responses and atopy has been observed in Japanese children, indicating that BCG immunisation, subclinical exposure to Mycobacterium tuberculosis without clinical disease, or host characteristics may influence the T helper (Th) lymphocyte balance with decreased atopy as a result. This study was undertaken to determine whether tuberculin reactivity is inversely related to atopy in young adults vaccinated with BCG at the age of 14. Methods-Men and women aged 20-44 years were tested using the adrenaline-Pirquet test with Norwegian produced synthetic medium tuberculin (n = 891). In addition, their serum total and specific IgE antibodies against mite, cat, timothy grass, mould and birch were measured. Results-Of the 574 subjects with complete examinations, 64% had a positive adrenaline-Pirquet tuberculin test (greater than or equal to 4 mm) and 27% exhibited IgE antibodies (greater than or equal to 0.35 kU/l) to one or more of the five specific allergens. The geometric mean of total serum IgE in the population was 30.2 kU/l. Tuberculin reactivity and log IgE were not correlated (r = 0.043, p 0.30). The mean tuberculin reactivity was 4.6 mm, 4.9 mm, and 5.0 mm in the lower, middle and upper tertile of IgE distribution (< 14 kU/l, 14-61 kU/l, > 61 kU/l). The prevalence of atopy, as assessed by either the presence of any of the five specific IgE antibodies or by each specific IgE antibody separately, did not differ between subjects with a positive and those with a negative tuberculin test. These results persisted after adjustment for age, sex, and smoking status in multivariate logistic regression analyses. Conclusions-In this young adult population, BCG vaccinated at the age of 14, no significant relationship between a positive tuberculin reaction and atopy was observed. If a true relationship had been found, our study suggests that it may be limited to populations immunised in early childhood when a substantial modulation of the immune system can occur.	22	72	2000	5	10.1136/thorax.55.6.454	Respiratory System
Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease. Previous work has shown an increase in CD8+ T-cells, neutrophils and eosinophils in small airway subepithelium in smokers, The authors have now investigated whether similar changes occur in the large airways. Immunohistochemistry on frozen sections of bronchial biopsies were obtained at bronchoscopy in 11 nonsmokers, eight asymptomatic smokers and 11 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD). There was an increase in the number of CD8+ cells infiltrating the bronchial subepithelium in the COPD group compared to the asymptomatic smokers (305 (109-400) versus 92 (41-550) cells.mm(-2), p=0.030). There was a negative correlation between the number of CD8+ cells and the forced expiratory volume in one second (FEV1) %predicted (p=0.005, r=-0.62), and a positive correlation between the number of CD8+ cells and the number of pack years smoked (p=0.017, r=0.42). There was a negative correlation between the activated/total eosinophils ratio and the FEV1 % pred (p=0.017, r=-0.51). There was a negative correlation between pack years smoked and the number of neutrophils (p=0.022, r=-0.36). Smokers who develop chronic obstructive pulmonary disease have increased numbers of CD8+ T-cells in large airways when compared to asymptomatic smokers. Airway obstruction was associated with an increase in the proportion of eosinophils that were activated.. airway| chronic obstructive pulmonary disease| eosinophils| inflammation| lymphocytes| neutrophils|air-flow obstruction| chronic-bronchitis| bronchoalveolar lavage| peripheral airways| cell-populations| induced sputum| t-lymphocytes| inflammation| asthma| biopsies.	MAR-2000	airway| chronic obstructive pulmonary disease| eosinophils| inflammation| lymphocytes| neutrophils|air-flow obstruction| chronic-bronchitis| bronchoalveolar lavage| peripheral airways| cell-populations| induced sputum| t-lymphocytes| inflammation| asthma| biopsies	Lams, BEA; Sousa, AR; Rees, PJ; Lee, TH	Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease		EUROPEAN RESPIRATORY JOURNAL	airway; chronic obstructive pulmonary disease; eosinophils; inflammation; lymphocytes; neutrophils	AIR-FLOW OBSTRUCTION; CHRONIC-BRONCHITIS; BRONCHOALVEOLAR LAVAGE; PERIPHERAL AIRWAYS; CELL-POPULATIONS; INDUCED SPUTUM; T-LYMPHOCYTES; INFLAMMATION; ASTHMA; BIOPSIES	Previous work has shown an increase in CD8+ T-cells, neutrophils and eosinophils in small airway subepithelium in smokers, The authors have now investigated whether similar changes occur in the large airways. Immunohistochemistry on frozen sections of bronchial biopsies were obtained at bronchoscopy in 11 nonsmokers, eight asymptomatic smokers and 11 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD). There was an increase in the number of CD8+ cells infiltrating the bronchial subepithelium in the COPD group compared to the asymptomatic smokers (305 (109-400) versus 92 (41-550) cells.mm(-2), p=0.030). There was a negative correlation between the number of CD8+ cells and the forced expiratory volume in one second (FEV1) %predicted (p=0.005, r=-0.62), and a positive correlation between the number of CD8+ cells and the number of pack years smoked (p=0.017, r=0.42). There was a negative correlation between the activated/total eosinophils ratio and the FEV1 % pred (p=0.017, r=-0.51). There was a negative correlation between pack years smoked and the number of neutrophils (p=0.022, r=-0.36). Smokers who develop chronic obstructive pulmonary disease have increased numbers of CD8+ T-cells in large airways when compared to asymptomatic smokers. Airway obstruction was associated with an increase in the proportion of eosinophils that were activated.	28	72	2000	5	10.1034/j.1399-3003.2000.15.14.x	Respiratory System
Dendritic cells and airway epithelial cells at the interface between innate and adaptive immune responses. P>Because they can recognize and sample inhaled allergens, dendritic cells (DC) have been shown to be responsible for the initiation and maintenance of adaptive Th2 responses in asthma. It is increasingly clear that DC functions are strongly influenced by a crosstalk with neighboring cells like epithelial cells. Whereas the epithelium was initially considered only as a barrier, it is now seen as a central player in controlling the function of lung DCs through release of innate cytokines-promoting Th2 responses. Clinically relevant allergens, as well as known environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells and DC. A better understanding of these interactions might lead to a better prevention and ultimately to new treatments for asthma.. allergens| asthma| dendritic cells| epithelium|house-dust mite| thymic stromal lymphopoietin| regulatory t-cells| helper type-2 response| bronchial lymph-node| in-vivo| allergic inflammation| inhaled antigen| respiratory-tract| th2 responses.	MAY-2011	allergens| asthma| dendritic cells| epithelium|house-dust mite| thymic stromal lymphopoietin| regulatory t-cells| helper type-2 response| bronchial lymph-node| in-vivo| allergic inflammation| inhaled antigen| respiratory-tract| th2 responses	Hammad, H; Lambrecht, BN	Dendritic cells and airway epithelial cells at the interface between innate and adaptive immune responses		ALLERGY	allergens; asthma; dendritic cells; epithelium	HOUSE-DUST MITE; THYMIC STROMAL LYMPHOPOIETIN; REGULATORY T-CELLS; HELPER TYPE-2 RESPONSE; BRONCHIAL LYMPH-NODE; IN-VIVO; ALLERGIC INFLAMMATION; INHALED ANTIGEN; RESPIRATORY-TRACT; TH2 RESPONSES	P>Because they can recognize and sample inhaled allergens, dendritic cells (DC) have been shown to be responsible for the initiation and maintenance of adaptive Th2 responses in asthma. It is increasingly clear that DC functions are strongly influenced by a crosstalk with neighboring cells like epithelial cells. Whereas the epithelium was initially considered only as a barrier, it is now seen as a central player in controlling the function of lung DCs through release of innate cytokines-promoting Th2 responses. Clinically relevant allergens, as well as known environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells and DC. A better understanding of these interactions might lead to a better prevention and ultimately to new treatments for asthma.	115	71	2011	9	10.1111/j.1398-9995.2010.02528.x	Allergy; Immunology
Large scale questionnaire survey on respiratory health in Sweden: Effects of late- and non-response. Background: Participation rates in epidemiologic studies conducted with postal questionnaires have steadily declined since 1970s. This can lead to an increased risk for selection bias. The aim of this study was to examine cause and effect of non-response in a large cross sectional study assessing respiratory health in western Sweden. Methods: The study sample was 29,218. The response rate to the initial postal. questionnaire was 33%. The response rates to subsequent postal reminders were 15%, 7% and 7% of eligible participants totalling a participation of 62%. Of those who did not respond to the postal survey, a random sample of 400 subjects were identified and contacted for interview by telephone. Results: Non-responders did not differ significantly in prevalence of airway diseases or symptoms when compared with responders. Mate sex, young age and smokers were underestimated among non-responders. No clear trends in prevalence of respiratory symptoms and report of asthma were found with delayed response to the postal. survey. The proportion of smokers and men increased with increasing number of reminders. Letters reminding subjects about the study did increase the participation rate but did not alter the risk estimates. Conclusion: We conclude that with a response rate of 62%, our estimate of disease and symptom prevalence was not biased in this Swedish population. However, smoking was underestimated. No general. trend for late-responders was seen and therefore we conclude that extrapolation of results to non-responders is not possible in our study. Causes of non-response were mainly due to circumstantial factors. (C) 2009 Elsevier Ltd. All rights reserved.. asthma| allergy| questionnaire| non-response| epidemiology|postal survey| risk-factors| young-adults| symptoms| asthma| prevalence| population| exposure| disease| cohort.	DEC-2009	asthma| allergy| questionnaire| non-response| epidemiology|postal survey| risk-factors| young-adults| symptoms| asthma| prevalence| population| exposure| disease| cohort	Ronmark, EP; Ekerljung, L; Lotvall, J; Toren, K; Ronmark, E; Lundback, B	Large scale questionnaire survey on respiratory health in Sweden: Effects of late- and non-response		RESPIRATORY MEDICINE	Asthma; Allergy; Questionnaire; Non-response; Epidemiology	POSTAL SURVEY; RISK-FACTORS; YOUNG-ADULTS; SYMPTOMS; ASTHMA; PREVALENCE; POPULATION; EXPOSURE; DISEASE; COHORT	Background: Participation rates in epidemiologic studies conducted with postal questionnaires have steadily declined since 1970s. This can lead to an increased risk for selection bias. The aim of this study was to examine cause and effect of non-response in a large cross sectional study assessing respiratory health in western Sweden. Methods: The study sample was 29,218. The response rate to the initial postal. questionnaire was 33%. The response rates to subsequent postal reminders were 15%, 7% and 7% of eligible participants totalling a participation of 62%. Of those who did not respond to the postal survey, a random sample of 400 subjects were identified and contacted for interview by telephone. Results: Non-responders did not differ significantly in prevalence of airway diseases or symptoms when compared with responders. Mate sex, young age and smokers were underestimated among non-responders. No clear trends in prevalence of respiratory symptoms and report of asthma were found with delayed response to the postal. survey. The proportion of smokers and men increased with increasing number of reminders. Letters reminding subjects about the study did increase the participation rate but did not alter the risk estimates. Conclusion: We conclude that with a response rate of 62%, our estimate of disease and symptom prevalence was not biased in this Swedish population. However, smoking was underestimated. No general. trend for late-responders was seen and therefore we conclude that extrapolation of results to non-responders is not possible in our study. Causes of non-response were mainly due to circumstantial factors. (C) 2009 Elsevier Ltd. All rights reserved.	29	71	2009	9	10.1016/j.rmed.2009.07.014	Cardiovascular System & Cardiology; Respiratory System
Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure. Background: Filaggrin gene (FLG) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear. Methods: FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort (n = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure. Results: The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4-2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8-7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early-life cat exposure (ORs being 8.2; 95% CI: 2.6-25.9, 6.0; 95% CI: 3.2-11.3 and 5.4; 95% CI: 1.2-23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5-10.5). Conclusions: FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization.. asthma| atopy| children| eczema| filaggrin|atopic-dermatitis| ichthyosis vulgaris| rare mutations| predispose| gene| population| expression| validation| prevalent| children.	DEC-2009	asthma| atopy| children| eczema| filaggrin|atopic-dermatitis| ichthyosis vulgaris| rare mutations| predispose| gene| population| expression| validation| prevalent| children	Schuttelaar, MLA; Kerkhof, M; Jonkman, MF; Koppelman, GH; Brunekreef, B; de Jongste, JC; Wijga, A; McLean, WHI; Postma, DS	Filaggrin mutations in the onset of eczema, sensitization, asthma, hay fever and the interaction with cat exposure		ALLERGY	asthma; atopy; children; eczema; filaggrin	ATOPIC-DERMATITIS; ICHTHYOSIS VULGARIS; RARE MUTATIONS; PREDISPOSE; GENE; POPULATION; EXPRESSION; VALIDATION; PREVALENT; CHILDREN	Background: Filaggrin gene (FLG) mutations contribute to the development of eczema and asthma, but their contribution to sensitization and hay fever remains unclear. Methods: FLG mutations R501X, 2282del4 and R2447X were genotyped in the Prevention and Incidence of Asthma and Mite Allergy birth cohort (n = 934) to evaluate longitudinally, for up to 8 years, their association with eczema, sensitization, asthma, hay fever and their interaction with cat exposure. Results: The combined FLG mutations were significantly associated with eczema at all ages when occurring in the first year of life (OR = 2.0; 95% CI: 1.4-2.8). Combined FLG mutations were associated with both atopic and nonatopic eczema, as well as asthma (OR = 3.7; 95% CI: 1.8-7.5). When the FLG 2282del4 mutation was analysed separately, it was significantly associated with the development of eczema during the first year, having eczema up to 8 years and sensitization at the age of 8 years, which was enhanced by early-life cat exposure (ORs being 8.2; 95% CI: 2.6-25.9, 6.0; 95% CI: 3.2-11.3 and 5.4; 95% CI: 1.2-23.6 respectively). FLG 2282del4 was significantly associated with hay fever from the age 5 years onwards (OR = 3.9; 95% CI: 1.5-10.5). Conclusions: FLG mutations are associated both with atopic and nonatopic eczema starting in the first year of life. FLG mutations combined with eczema in the first year of life are associated with a later development of asthma and hay fever, a clear example of the atopic march. We confirm that cat exposure enhances the effect of a FLG mutation on the development of eczema and sensitization.	27	71	2009	8	10.1111/j.1398-9995.2009.02080.x	Allergy; Immunology
The occupant as a source of house dust bacteria. Background: Markers for microbial groups are commonly measured in house dust samples to assess indoor exposure to microbes in studies on asthma and allergy. However, little is known about the sources of different microbes. A better understanding of the nature and origin of microbes present in the immediate environment of human beings is crucial if one wants to elucidate protective as well as adverse effects on human health. Objective: To determine the extent to which the bacterial composition of mattress and floor dust reflects the presence of the human body in relation to other environmental sources. Methods: House dust and skin surface swab samples of occupants in 4 homes were collected and analyzed for their bacterial content, using a culture-independent methodology. Bacterial sequences analyzed from the different house dusts and skin surface swabs represented random samples of bacteria present in a given sample. Highly similar sequences were grouped to assess biodiversity and to draw conclusions about the sources of bacteria. Results: The bacterial flora in the house dust samples was found to be highly diverse and dominated by gram-positive bacteria. To a considerable extent, the presence of different bacterial groups was attributed to human sources. In the individuals' mattress dust samples, 69% to 88% of the bacterial sequences analyzed were associated with human origins. The respective percentages for the individual floor dusts ranged from 45% to 55%. Conclusion: Our study indicates that human-derived bacteria account for a large part of the mainly gram-positive bacterial content in house dust. (J Allergy Clin Immunol 2009;124:834-40.). microbial markers| mattress dust| floor dust| indoor| microbial exposure| bacteria| sequencing| endotoxin| lps| muramic acid|endotoxin exposure| school-children| farm children| birth cohort| diversity| culture| risk| determinants| environment| components.	OCT-2009	microbial markers| mattress dust| floor dust| indoor| microbial exposure| bacteria| sequencing| endotoxin| lps| muramic acid|endotoxin exposure| school-children| farm children| birth cohort| diversity| culture| risk| determinants| environment| components	Taubel, M; Rintala, H; Pitkaranta, M; Paulin, L; Laitinen, S; Pekkanen, J; Hyvarinen, A; Nevalainen, A	The occupant as a source of house dust bacteria		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Microbial markers; mattress dust; floor dust; indoor; microbial exposure; bacteria; sequencing; endotoxin; LPS; muramic acid	ENDOTOXIN EXPOSURE; SCHOOL-CHILDREN; FARM CHILDREN; BIRTH COHORT; DIVERSITY; CULTURE; RISK; DETERMINANTS; ENVIRONMENT; COMPONENTS	Background: Markers for microbial groups are commonly measured in house dust samples to assess indoor exposure to microbes in studies on asthma and allergy. However, little is known about the sources of different microbes. A better understanding of the nature and origin of microbes present in the immediate environment of human beings is crucial if one wants to elucidate protective as well as adverse effects on human health. Objective: To determine the extent to which the bacterial composition of mattress and floor dust reflects the presence of the human body in relation to other environmental sources. Methods: House dust and skin surface swab samples of occupants in 4 homes were collected and analyzed for their bacterial content, using a culture-independent methodology. Bacterial sequences analyzed from the different house dusts and skin surface swabs represented random samples of bacteria present in a given sample. Highly similar sequences were grouped to assess biodiversity and to draw conclusions about the sources of bacteria. Results: The bacterial flora in the house dust samples was found to be highly diverse and dominated by gram-positive bacteria. To a considerable extent, the presence of different bacterial groups was attributed to human sources. In the individuals' mattress dust samples, 69% to 88% of the bacterial sequences analyzed were associated with human origins. The respective percentages for the individual floor dusts ranged from 45% to 55%. Conclusion: Our study indicates that human-derived bacteria account for a large part of the mainly gram-positive bacterial content in house dust. (J Allergy Clin Immunol 2009;124:834-40.)	31	71	2009	7	10.1016/j.jaci.2009.07.045	Allergy; Immunology
Wheat allergy. Purpose of review This review describes the diverse clinical manifestations of IgE-mediated allergy to ingested wheat and summarizes recent advances in characterization of clinically significant allergens and diagnostic workup. Recent findings Recent population-based studies have shown the prevalence of wheat allergy and sensitization more precisely than past studies among small populations and in hospital settings. Intensive research has demonstrated the diverse profile of both water/salt-soluble and insoluble allergens involved in clinical types of wheat allergies determined depending on the patient age, the sensitization route, and the protein state during the exposure. Consequently, some new allergens, including nonspecific lipid transfer protein (Tri a 14), have been identified. For diagnosis, the role of water/salt-insoluble gliadins, particularly omega-5 gliadin, a major allergen of wheat-dependent, exercise-induced anaphylaxis, was assessed as compared with the results of oral challenges. The mechanisms of eliciting anaphylactic symptoms by exercise in wheat-de pendent, exercise-induced anaphylaxis were speculated upon; one is the allergenicity strengthened by activated tissue transglutaminase and another is the increased absorption of allergens through the gastrointestinal tract. Summary Findings of the recent studies show potential for more precise diagnosis in each clinical type of wheat allergies.. allergen| exercise-induced anaphylaxis| food-dependent| gliadin| ige| wheat allergy|exercise-induced anaphylaxis| controlled food challenge| omega-5 gliadin| ige-antibodies| atopic-dermatitis| major allergen| 4-year-old children| proteomic analysis| cereal-grains| double-blind.	JUN-2009	allergen| exercise-induced anaphylaxis| food-dependent| gliadin| ige| wheat allergy|exercise-induced anaphylaxis| controlled food challenge| omega-5 gliadin| ige-antibodies| atopic-dermatitis| major allergen| 4-year-old children| proteomic analysis| cereal-grains| double-blind	Inomata, N	Wheat allergy		CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY	allergen; exercise-induced anaphylaxis; food-dependent; gliadin; IgE; wheat allergy	EXERCISE-INDUCED ANAPHYLAXIS; CONTROLLED FOOD CHALLENGE; OMEGA-5 GLIADIN; IGE-ANTIBODIES; ATOPIC-DERMATITIS; MAJOR ALLERGEN; 4-YEAR-OLD CHILDREN; PROTEOMIC ANALYSIS; CEREAL-GRAINS; DOUBLE-BLIND	Purpose of review This review describes the diverse clinical manifestations of IgE-mediated allergy to ingested wheat and summarizes recent advances in characterization of clinically significant allergens and diagnostic workup. Recent findings Recent population-based studies have shown the prevalence of wheat allergy and sensitization more precisely than past studies among small populations and in hospital settings. Intensive research has demonstrated the diverse profile of both water/salt-soluble and insoluble allergens involved in clinical types of wheat allergies determined depending on the patient age, the sensitization route, and the protein state during the exposure. Consequently, some new allergens, including nonspecific lipid transfer protein (Tri a 14), have been identified. For diagnosis, the role of water/salt-insoluble gliadins, particularly omega-5 gliadin, a major allergen of wheat-dependent, exercise-induced anaphylaxis, was assessed as compared with the results of oral challenges. The mechanisms of eliciting anaphylactic symptoms by exercise in wheat-de pendent, exercise-induced anaphylaxis were speculated upon; one is the allergenicity strengthened by activated tissue transglutaminase and another is the increased absorption of allergens through the gastrointestinal tract. Summary Findings of the recent studies show potential for more precise diagnosis in each clinical type of wheat allergies.	57	71	2009	6	10.1097/ACI.0b013e32832aa5bc	Allergy; Immunology
An interaction between filaggrin mutations and early food sensitization improves the prediction of childhood asthma. Background: Asthma prediction in early infancy is essential for the development of new preventive strategies. Loss-of-function mutations in the filaggrin gene (FLG) were identified as risk factors for eczema and associated asthma. Objective: We evaluated the utility of the FLG mutations for the prediction of asthma. Methods: Eight hundred seventy-one individuals of the prospective German Multicenter Allergy Study cohort were genotyped for 3 FLG mutations. Information on asthma, eczema, and food sensitization was available from birth to 13 years of age. Pulmonary function was measured from 7 to 13 years of age. The predictive value of the FLG mutations and of atopic phenotypes in infancy was assessed for asthma. Results: In infants with eczema and sensitization to food allergens, the FLG mutations predicted childhood asthma with a positive predictive value of 100% (95% CI, 65.5% to 100%). This subgroup was characterized by a significant decrease in pulmonary function until puberty and represented 8.1% of all asthmatic children and 19.1% of patients with asthma after infantile eczema. We found a strong synergistic interaction between the FLG-null alleles and early food sensitization in the disease transition from eczema to asthma (relative excess risk due to interaction, 2.64; 95% CI, 1.70-3.98; P = .00040). Conclusion: FLG mutations and food sensitization represent 2 distinct mechanisms interacting in the pathogenesis of asthma. In infants with eczema and food sensitization, genotyping of the FLG mutations allows the prediction of asthma before the onset of symptoms. Our findings might facilitate the development of early subgroup-specific interventions to prevent the progression from eczema to asthma. (J Allergy Clin Immunol 2009;123:911-6.). genetic prediction| interaction| asthma| eczema| food sensitization| filaggrin| mutations| subphenotype| prevention| pulmonary function|1st 6 years| atopic-dermatitis| allergic rhinitis| natural course| dust-mite| follow-up| risk| life| disease| cohort.	APR-2009	genetic prediction| interaction| asthma| eczema| food sensitization| filaggrin| mutations| subphenotype| prevention| pulmonary function|1st 6 years| atopic-dermatitis| allergic rhinitis| natural course| dust-mite| follow-up| risk| life| disease| cohort	Marenholz, I; Kerscher, T; Bauerfeind, A; Esparza-Gordillo, J; Nickel, R; Keil, T; Lau, S; Rohde, K; Wahn, U; Lee, YA	An interaction between filaggrin mutations and early food sensitization improves the prediction of childhood asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Genetic prediction; interaction; asthma; eczema; food sensitization; filaggrin; mutations; subphenotype; prevention; pulmonary function	1ST 6 YEARS; ATOPIC-DERMATITIS; ALLERGIC RHINITIS; NATURAL COURSE; DUST-MITE; FOLLOW-UP; RISK; LIFE; DISEASE; COHORT	Background: Asthma prediction in early infancy is essential for the development of new preventive strategies. Loss-of-function mutations in the filaggrin gene (FLG) were identified as risk factors for eczema and associated asthma. Objective: We evaluated the utility of the FLG mutations for the prediction of asthma. Methods: Eight hundred seventy-one individuals of the prospective German Multicenter Allergy Study cohort were genotyped for 3 FLG mutations. Information on asthma, eczema, and food sensitization was available from birth to 13 years of age. Pulmonary function was measured from 7 to 13 years of age. The predictive value of the FLG mutations and of atopic phenotypes in infancy was assessed for asthma. Results: In infants with eczema and sensitization to food allergens, the FLG mutations predicted childhood asthma with a positive predictive value of 100% (95% CI, 65.5% to 100%). This subgroup was characterized by a significant decrease in pulmonary function until puberty and represented 8.1% of all asthmatic children and 19.1% of patients with asthma after infantile eczema. We found a strong synergistic interaction between the FLG-null alleles and early food sensitization in the disease transition from eczema to asthma (relative excess risk due to interaction, 2.64; 95% CI, 1.70-3.98; P = .00040). Conclusion: FLG mutations and food sensitization represent 2 distinct mechanisms interacting in the pathogenesis of asthma. In infants with eczema and food sensitization, genotyping of the FLG mutations allows the prediction of asthma before the onset of symptoms. Our findings might facilitate the development of early subgroup-specific interventions to prevent the progression from eczema to asthma. (J Allergy Clin Immunol 2009;123:911-6.)	37	71	2009	6	10.1016/j.jaci.2009.01.051	Allergy; Immunology
Early introduction of fish decreases the risk of eczema in infants. Background: Atopic eczema in infants has increased in western societies. Environmental factors and the introduction of food may affect the risk of eczema. Aims: To investigate the prevalence of eczema among infants in western Sweden, describe patterns of food introduction and assess risk factors for eczema at 1 year of age. Methods: Data were obtained from a prospective, longitudinal cohort study of infants born in western Sweden in 2003; 8176 families were randomly selected and, 6 months after the infant's birth, were invited to participate and received questionnaires. A second questionnaire was sent out when the infants were 12 months old. Both questionnaires were completed and medical birth register data were obtained for 4921 infants (60.2% of the selected population). Results: At 1 year of age, 20.9% of the infants had previous or current eczema. Median age at onset was 4 months. In multivariable analysis, familial occurrence of eczema, especially in siblings (OR 1.87; 95% confidence interval (CI) 1.50 to 2.33) or the mother (OR 1.54; 95% CI 1.30 to 1.84), remained an independent risk factor. Introducing fish before 9 months of age (OR 0.76; 95% CI 0.62 to 0.94) and having a bird in the home (OR 0.35; 95% CI 0.17 to 0.75) were beneficial. Conclusions: One in five infants suffer from eczema during the first year of life. Familial eczema increased the risk, while early fish introduction and bird keeping decreased it. Breast feeding and time of milk and egg introduction did not affect the risk.. atopic-dermatitis| birth cohort| 1st year| intestinal microflora| allergy development| preschool-children| childhood asthma| life| sensitization| association.	JAN-2009	atopic-dermatitis| birth cohort| 1st year| intestinal microflora| allergy development| preschool-children| childhood asthma| life| sensitization| association	Alm, B; Aberg, N; Erdes, L; Mollborg, P; Pettersson, R; Norvenius, SG; Goksor, E; Wennergren, G	Early introduction of fish decreases the risk of eczema in infants		ARCHIVES OF DISEASE IN CHILDHOOD		ATOPIC-DERMATITIS; BIRTH COHORT; 1ST YEAR; INTESTINAL MICROFLORA; ALLERGY DEVELOPMENT; PRESCHOOL-CHILDREN; CHILDHOOD ASTHMA; LIFE; SENSITIZATION; ASSOCIATION	Background: Atopic eczema in infants has increased in western societies. Environmental factors and the introduction of food may affect the risk of eczema. Aims: To investigate the prevalence of eczema among infants in western Sweden, describe patterns of food introduction and assess risk factors for eczema at 1 year of age. Methods: Data were obtained from a prospective, longitudinal cohort study of infants born in western Sweden in 2003; 8176 families were randomly selected and, 6 months after the infant's birth, were invited to participate and received questionnaires. A second questionnaire was sent out when the infants were 12 months old. Both questionnaires were completed and medical birth register data were obtained for 4921 infants (60.2% of the selected population). Results: At 1 year of age, 20.9% of the infants had previous or current eczema. Median age at onset was 4 months. In multivariable analysis, familial occurrence of eczema, especially in siblings (OR 1.87; 95% confidence interval (CI) 1.50 to 2.33) or the mother (OR 1.54; 95% CI 1.30 to 1.84), remained an independent risk factor. Introducing fish before 9 months of age (OR 0.76; 95% CI 0.62 to 0.94) and having a bird in the home (OR 0.35; 95% CI 0.17 to 0.75) were beneficial. Conclusions: One in five infants suffer from eczema during the first year of life. Familial eczema increased the risk, while early fish introduction and bird keeping decreased it. Breast feeding and time of milk and egg introduction did not affect the risk.	40	71	2009	5	10.1136/adc.2008.140418	Pediatrics
Cigarette Smoke, Inflammation, and Lung Injury: A Mechanistic Perspective. Inflammation is a common feature in the pathogenesis of cigarette smoke-associated diseases. The recruitment of inflammatory cells into the lung following cigarette smoke exposure presents a risk of tissue damage through the release of toxic mediators, including proteolytic enzymes and reactive oxygen species. This review represents a toxicological approach to investigation of cigarette smoke-induced lung injury, with a focus on laboratory studies and an emphasis on inflammatory mechanisms. The studies discussed in this review analyze the role of inflammation and inflammatory mediators in the development of injury. In cases where information relating to cigarette smoke is limited, examples are taken from other models of lung injury applicable to cigarette smoke. The primary aim of the review is to summarize published work so as to permit (1) an evaluation of chronic lung injury and inflammatory responses in animal models, (2) a discussion of inflammatory mediators in the development of chronic injury, and (3) identification of immunological mechanisms of injury. These studies discuss the currently understood roles of cytokines, cell adhesion molecules, and oxidative stress in inflammatory reactions and lung injury. A role for lipocortin 1 (annexin 1), a naturally occurring defense factor against inflammation, is discussed because of the possibility that impaired synthesis and degradation of lipocortin 1 will influence immune responses in animals exposed to cigarette smoke either by augmenting T helper cell Th1 response or by shifting Th1 to Th2 response. While Th1 augmentation will increase the risk for development of emphysema, Th1 to Th2 shift will favor development of asthma.. necrosis-factor-alpha| environmental tobacco-smoke| nf-kappa-b| induced pulmonary inflammation| bronchial epithelial-cells| connective-tissue breakdown| growth-factor-beta| intercellular-adhesion molecule-1| bronchoalveolar lavage fluid| inhibits cytokine production.	2009	necrosis-factor-alpha| environmental tobacco-smoke| nf-kappa-b| induced pulmonary inflammation| bronchial epithelial-cells| connective-tissue breakdown| growth-factor-beta| intercellular-adhesion molecule-1| bronchoalveolar lavage fluid| inhibits cytokine production	Bhalla, DK; Hirata, F; Rishi, AK; Gairola, CG	Cigarette Smoke, Inflammation, and Lung Injury: A Mechanistic Perspective		JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS		NECROSIS-FACTOR-ALPHA; ENVIRONMENTAL TOBACCO-SMOKE; NF-KAPPA-B; INDUCED PULMONARY INFLAMMATION; BRONCHIAL EPITHELIAL-CELLS; CONNECTIVE-TISSUE BREAKDOWN; GROWTH-FACTOR-BETA; INTERCELLULAR-ADHESION MOLECULE-1; BRONCHOALVEOLAR LAVAGE FLUID; INHIBITS CYTOKINE PRODUCTION	Inflammation is a common feature in the pathogenesis of cigarette smoke-associated diseases. The recruitment of inflammatory cells into the lung following cigarette smoke exposure presents a risk of tissue damage through the release of toxic mediators, including proteolytic enzymes and reactive oxygen species. This review represents a toxicological approach to investigation of cigarette smoke-induced lung injury, with a focus on laboratory studies and an emphasis on inflammatory mechanisms. The studies discussed in this review analyze the role of inflammation and inflammatory mediators in the development of injury. In cases where information relating to cigarette smoke is limited, examples are taken from other models of lung injury applicable to cigarette smoke. The primary aim of the review is to summarize published work so as to permit (1) an evaluation of chronic lung injury and inflammatory responses in animal models, (2) a discussion of inflammatory mediators in the development of chronic injury, and (3) identification of immunological mechanisms of injury. These studies discuss the currently understood roles of cytokines, cell adhesion molecules, and oxidative stress in inflammatory reactions and lung injury. A role for lipocortin 1 (annexin 1), a naturally occurring defense factor against inflammation, is discussed because of the possibility that impaired synthesis and degradation of lipocortin 1 will influence immune responses in animals exposed to cigarette smoke either by augmenting T helper cell Th1 response or by shifting Th1 to Th2 response. While Th1 augmentation will increase the risk for development of emphysema, Th1 to Th2 shift will favor development of asthma.	207	71	2009	20	10.1080/10937400802545094	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
A comprehensive evaluation of the enzymatic and nonenzymatic antioxidant systems in childhood asthma. Background: Even though there is ample evidence on the oxidative stress in asthma, there is limited information on the antioxidant defense systems. Objectives: To conduct a comprehensive evaluation of various components of both enzymatic and nonenzymatic antioxidants in a large group of children with asthma. Methods: A total of 164 children with mild asthma and 173 healthy children were included in the study. Levels of the enzymes glutathione peroxidase and superoxide dismutase were measured by using ELISA, whereas reduced glutathione, ascorbic acid, alpha-tocopherol, lycopene, beta-carotene, amino acids participating in glutathione synthesis, and amino acids susceptible to oxidation were measured by HPLC. All comparisons were adjusted for atopy, body mass index, smoke exposure, and pet ownership. Results: Levels of the enzymes glutathione peroxidase and superoxide dismutase and of the nonenzymatic components of the antioxidant system including reduced glutathione, ascorbic acid, alpha-tocopherol, lycopene, and beta-carotene were significantly lower in children with asthma compared with healthy controls (P <.001 for each). Of the amino acids contributing to glutathione synthesis, glycine and glutamine were significantly lower in children with asthma (P <.001). The majority of the amino acid susceptible to oxidative stress displayed lower levels in children with asthma (P <.05). Conclusion: Childhood asthma is associated with significant decreases in various components of both enzymatic and nonenzymatic antioxidant defenses.. amino acid| antioxidant| ascorbic acid| asthma| glutathione| glutathione peroxidase| lycopene| malondialdehyde| oxidative stress| superoxide dismutase| alpha-tocopherol| beta-carotene|extracellular-superoxide-dismutase| oxidative stress| amino-acids| protein oxidation| cysteine kinetics| plasma lycopene| free-radicals| glutathione| children| serum.	JUL-2008	amino acid| antioxidant| ascorbic acid| asthma| glutathione| glutathione peroxidase| lycopene| malondialdehyde| oxidative stress| superoxide dismutase| alpha-tocopherol| beta-carotene|extracellular-superoxide-dismutase| oxidative stress| amino-acids| protein oxidation| cysteine kinetics| plasma lycopene| free-radicals| glutathione| children| serum	Sackesen, C; Ercan, H; Dizdar, E; Soyer, O; Gumus, P; Tosun, BN; Buyuktuncer, Z; Karabulut, E; Besler, T; Kalayci, O	A comprehensive evaluation of the enzymatic and nonenzymatic antioxidant systems in childhood asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	amino acid; antioxidant; ascorbic acid; asthma; glutathione; glutathione peroxidase; lycopene; malondialdehyde; oxidative stress; superoxide dismutase; alpha-tocopherol; beta-carotene	EXTRACELLULAR-SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; AMINO-ACIDS; PROTEIN OXIDATION; CYSTEINE KINETICS; PLASMA LYCOPENE; FREE-RADICALS; GLUTATHIONE; CHILDREN; SERUM	Background: Even though there is ample evidence on the oxidative stress in asthma, there is limited information on the antioxidant defense systems. Objectives: To conduct a comprehensive evaluation of various components of both enzymatic and nonenzymatic antioxidants in a large group of children with asthma. Methods: A total of 164 children with mild asthma and 173 healthy children were included in the study. Levels of the enzymes glutathione peroxidase and superoxide dismutase were measured by using ELISA, whereas reduced glutathione, ascorbic acid, alpha-tocopherol, lycopene, beta-carotene, amino acids participating in glutathione synthesis, and amino acids susceptible to oxidation were measured by HPLC. All comparisons were adjusted for atopy, body mass index, smoke exposure, and pet ownership. Results: Levels of the enzymes glutathione peroxidase and superoxide dismutase and of the nonenzymatic components of the antioxidant system including reduced glutathione, ascorbic acid, alpha-tocopherol, lycopene, and beta-carotene were significantly lower in children with asthma compared with healthy controls (P <.001 for each). Of the amino acids contributing to glutathione synthesis, glycine and glutamine were significantly lower in children with asthma (P <.001). The majority of the amino acid susceptible to oxidative stress displayed lower levels in children with asthma (P <.05). Conclusion: Childhood asthma is associated with significant decreases in various components of both enzymatic and nonenzymatic antioxidant defenses.	50	71	2008	8	10.1016/j.jaci.2008.03.035	Allergy; Immunology
The effect of sandstorms and air pollution on cause-specific hospital admissions in Taipei, Taiwan. Objective: Relatively little research exists focusing on the impact of air pollution on hospital admissions in Asia compared to the extensive work conducted in the USA and Europe. The issue is of particular importance because of the frequency, intensity and health effects of Asian sandstorms. This work investigates the relation between cause-specific hospital admissions and sandstorms and air pollution in Taipei, Taiwan's capital. Methods: Time-series analyses of asthma, pneumonia, ischaemic heart disease and cerebrovascular disease hospital admissions were performed for Taipei. An eight-year time period (1995-2002) was considered for various indicators of sandstorms and the pollutants NO2, CO, ozone, SO2, PM10, and PM2.5. Pollution effects based on single-day lags of 0, 1, 2 and 3 days were explored, along with the average of the same day and previous three days (L03). Results: The risk of ischaemic heart disease admissions was associated with several sandstorm metrics, including indicators of high PM10 levels in the Taipei area, indicators of high PM10 at a monitor designed to measure background pollution, the PM coarse fraction, and the ratio of PM10 to PM2.5. However, the lag structure of effect was not consistent across sandstorm indicators. Hospital admissions for this disease were 16-21% higher on sandstorm days compared to other days. This cause was also associated with transportation-related pollutants, NO2, CO and PM2.5. Asthma admissions rose 4.48% (95% CI 0.71% to 8.38%) per 28 mu g/m(3) increase in L03 PM10 levels and 7.60% (95% CI 2.87% to 12.54%) per 10 ppb increase in L03 ozone. Cerebrovascular disease admissions were associated with PM10 and CO, both at lag 3 days. SO2 exhibited no relation with admissions. Conclusions: Risk of hospital admissions in Taipei may be increased by air pollution and sandstorms. Additional research is needed to clarify the lag structure and magnitude of such effects.. dust storm events| daily stroke admissions| long-range transport| daily mortality| cardiovascular-disease| ambient air| particles| quality| particulate| kaohsiung.	FEB-2008	dust storm events| daily stroke admissions| long-range transport| daily mortality| cardiovascular-disease| ambient air| particles| quality| particulate| kaohsiung	Bell, ML; Levy, JK; Lin, Z	The effect of sandstorms and air pollution on cause-specific hospital admissions in Taipei, Taiwan		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		DUST STORM EVENTS; DAILY STROKE ADMISSIONS; LONG-RANGE TRANSPORT; DAILY MORTALITY; CARDIOVASCULAR-DISEASE; AMBIENT AIR; PARTICLES; QUALITY; PARTICULATE; KAOHSIUNG	Objective: Relatively little research exists focusing on the impact of air pollution on hospital admissions in Asia compared to the extensive work conducted in the USA and Europe. The issue is of particular importance because of the frequency, intensity and health effects of Asian sandstorms. This work investigates the relation between cause-specific hospital admissions and sandstorms and air pollution in Taipei, Taiwan's capital. Methods: Time-series analyses of asthma, pneumonia, ischaemic heart disease and cerebrovascular disease hospital admissions were performed for Taipei. An eight-year time period (1995-2002) was considered for various indicators of sandstorms and the pollutants NO2, CO, ozone, SO2, PM10, and PM2.5. Pollution effects based on single-day lags of 0, 1, 2 and 3 days were explored, along with the average of the same day and previous three days (L03). Results: The risk of ischaemic heart disease admissions was associated with several sandstorm metrics, including indicators of high PM10 levels in the Taipei area, indicators of high PM10 at a monitor designed to measure background pollution, the PM coarse fraction, and the ratio of PM10 to PM2.5. However, the lag structure of effect was not consistent across sandstorm indicators. Hospital admissions for this disease were 16-21% higher on sandstorm days compared to other days. This cause was also associated with transportation-related pollutants, NO2, CO and PM2.5. Asthma admissions rose 4.48% (95% CI 0.71% to 8.38%) per 28 mu g/m(3) increase in L03 PM10 levels and 7.60% (95% CI 2.87% to 12.54%) per 10 ppb increase in L03 ozone. Cerebrovascular disease admissions were associated with PM10 and CO, both at lag 3 days. SO2 exhibited no relation with admissions. Conclusions: Risk of hospital admissions in Taipei may be increased by air pollution and sandstorms. Additional research is needed to clarify the lag structure and magnitude of such effects.	40	71	2008	8	10.1136/oem.2006.031500	Public, Environmental & Occupational Health
Exhaled nitric oxide in childhood asthma: a review. As an 'inflammometer', the fraction of nitric oxide in exhaled air (FENO) is increasingly used in the management of paediatric asthma. FENO provides us with valuable, additional information regarding the nature of underlying airway inflammation, and complements lung function testing and measurement of airway hyper-reactivity. This review focuses on clinical applications of FENO in paediatric asthma. First, FENO provides us with a practical tool to aid in the diagnosis of asthma and distinguish patients who will benefit from inhaled corticosteroids from those who will not. Second, FENO is helpful in predicting exacerbations, and predicting successful steroid reduction or withdrawal. In atopic asthmatic children FENO is beneficial in adjusting steroid doses, discerning those patients who require additional therapy from those whose medication dose could feasibly be reduced. In pre-school children FENO may be of help in the differential diagnosis of respiratory symptoms, and may potentially allow for better targeting and monitoring of anti-inflammatory treatment.. primary ciliary dyskinesia| bronchiolitis obliterans syndrome| experimental rhinovirus infection| respiratory syncytial virus| airway epithelial-cells| grass-pollen exposure| school-age-children| cystic-fibrosis| lung-function| healthy-children.	FEB-2008	primary ciliary dyskinesia| bronchiolitis obliterans syndrome| experimental rhinovirus infection| respiratory syncytial virus| airway epithelial-cells| grass-pollen exposure| school-age-children| cystic-fibrosis| lung-function| healthy-children	Pijnenburg, MWH; De Jongste, JC	Exhaled nitric oxide in childhood asthma: a review		CLINICAL AND EXPERIMENTAL ALLERGY		PRIMARY CILIARY DYSKINESIA; BRONCHIOLITIS OBLITERANS SYNDROME; EXPERIMENTAL RHINOVIRUS INFECTION; RESPIRATORY SYNCYTIAL VIRUS; AIRWAY EPITHELIAL-CELLS; GRASS-POLLEN EXPOSURE; SCHOOL-AGE-CHILDREN; CYSTIC-FIBROSIS; LUNG-FUNCTION; HEALTHY-CHILDREN	As an 'inflammometer', the fraction of nitric oxide in exhaled air (FENO) is increasingly used in the management of paediatric asthma. FENO provides us with valuable, additional information regarding the nature of underlying airway inflammation, and complements lung function testing and measurement of airway hyper-reactivity. This review focuses on clinical applications of FENO in paediatric asthma. First, FENO provides us with a practical tool to aid in the diagnosis of asthma and distinguish patients who will benefit from inhaled corticosteroids from those who will not. Second, FENO is helpful in predicting exacerbations, and predicting successful steroid reduction or withdrawal. In atopic asthmatic children FENO is beneficial in adjusting steroid doses, discerning those patients who require additional therapy from those whose medication dose could feasibly be reduced. In pre-school children FENO may be of help in the differential diagnosis of respiratory symptoms, and may potentially allow for better targeting and monitoring of anti-inflammatory treatment.	198	71	2008	14	10.1111/j.1365-2222.2007.02897.x	Allergy; Immunology
Risk factors for persistent pulmonary hypertension of the newborn. Objective. Persistent pulmonary hypertension of the newborn, a clinical syndrome that results from the failure of the normal fetal-to-neonatal circulatory transition, is associated with substantial infant mortality and morbidity. We performed a case-control study to determine possible antenatal and perinatal predictors of persistent pulmonary hypertension of the newborn. Methods. Between 1998 and 2003, the Slone Epidemiology Center enrolled 377 mothers of infants with persistent pulmonary hypertension of the newborn and 836 mothers of matched control subjects. Within 6 months of delivery, study nurses interviewed participants regarding demographic, medical, and obstetric characteristics. Results. Factors that were independently associated with an elevated risk for persistent pulmonary hypertension of the newborn were infant male gender and black or Asian maternal race compared with white race. High prepregnancy BMI (> 27 vs < 20) was also associated with persistent pulmonary hypertension of the newborn, as were diabetes and asthma. Compared with infants who were delivered vaginally, the risk for persistent pulmonary hypertension of the newborn was higher for those who were born by cesarean section. Compared with infants who were born within 37 to 41 gestational weeks, the risk was higher for those who were born between 34 and 37 completed weeks and for those born beyond 41 weeks. Compared with infants within the 10th and 90th percentiles of birth weight for gestational age distribution, the risk was higher for infants above the 90th percentile. Conclusions. Our findings suggest an increased risk for persistent pulmonary hypertension of the newborn associated with cesarean delivery; late preterm or postterm birth; being large for gestational age; and maternal black or Asian race, overweight, diabetes, and asthma. It remains unclear whether some of these factors are direct causes of persistent pulmonary hypertension of the newborn or simply share common causes with it; however, clinicians should be alert to the increased need for monitoring and intervention among pregnancies with these risk factors.. pulmonary hypertension| newborn| pphn| epidemiology| race| bmi| cesarean section|extracorporeal membrane-oxygenation| neonatal respiratory morbidity| elective cesarean-section| birth-defects| nitric-oxide| delivery| labor| pregnancy| term| exposure.	AUG-2007	pulmonary hypertension| newborn| pphn| epidemiology| race| bmi| cesarean section|extracorporeal membrane-oxygenation| neonatal respiratory morbidity| elective cesarean-section| birth-defects| nitric-oxide| delivery| labor| pregnancy| term| exposure	Hernandez-Diaz, S; Van Marter, LJ; Werler, MM; Louik, C; Mitchell, AA	Risk factors for persistent pulmonary hypertension of the newborn		PEDIATRICS	pulmonary hypertension; newborn; PPHN; epidemiology; race; BMI; Cesarean section	EXTRACORPOREAL MEMBRANE-OXYGENATION; NEONATAL RESPIRATORY MORBIDITY; ELECTIVE CESAREAN-SECTION; BIRTH-DEFECTS; NITRIC-OXIDE; DELIVERY; LABOR; PREGNANCY; TERM; EXPOSURE	Objective. Persistent pulmonary hypertension of the newborn, a clinical syndrome that results from the failure of the normal fetal-to-neonatal circulatory transition, is associated with substantial infant mortality and morbidity. We performed a case-control study to determine possible antenatal and perinatal predictors of persistent pulmonary hypertension of the newborn. Methods. Between 1998 and 2003, the Slone Epidemiology Center enrolled 377 mothers of infants with persistent pulmonary hypertension of the newborn and 836 mothers of matched control subjects. Within 6 months of delivery, study nurses interviewed participants regarding demographic, medical, and obstetric characteristics. Results. Factors that were independently associated with an elevated risk for persistent pulmonary hypertension of the newborn were infant male gender and black or Asian maternal race compared with white race. High prepregnancy BMI (> 27 vs < 20) was also associated with persistent pulmonary hypertension of the newborn, as were diabetes and asthma. Compared with infants who were delivered vaginally, the risk for persistent pulmonary hypertension of the newborn was higher for those who were born by cesarean section. Compared with infants who were born within 37 to 41 gestational weeks, the risk was higher for those who were born between 34 and 37 completed weeks and for those born beyond 41 weeks. Compared with infants within the 10th and 90th percentiles of birth weight for gestational age distribution, the risk was higher for infants above the 90th percentile. Conclusions. Our findings suggest an increased risk for persistent pulmonary hypertension of the newborn associated with cesarean delivery; late preterm or postterm birth; being large for gestational age; and maternal black or Asian race, overweight, diabetes, and asthma. It remains unclear whether some of these factors are direct causes of persistent pulmonary hypertension of the newborn or simply share common causes with it; however, clinicians should be alert to the increased need for monitoring and intervention among pregnancies with these risk factors.	33	71	2007	11	10.1542/peds.2006-3037	Pediatrics
Specificity of basement membrane thickening in severe asthma. Background: Reticular basement membrane (RBM) thickness is considered a hallmark for airway remodeling in airway diseases such as asthma. It is still unclear whether this measurement could be associated with disease severity or apply to chronic obstructive pulmonary disease (COPD). A wide range of results, at baseline or after therapeutic intervention, have been reported using different measurement methods. Objective: To determine whether increased RBM thickness could be associated specifically with severe asthma and in COPD in large samples. Methods: We blindly measured RBM thickness in endobronchial biopsies from 50 patients with severe asthma (mean age, 53 years; FEV1 66% predicted, inhaled steroids >= 1500 mu g and 20 mg daily dose of oral corticosteroids, lifelong nonsmokers), 50 untreated patients with mild asthma mean age, 33 years; FEV, 93%pred, lifelong nonsmokers), 50 patients with COPD (mean age, 57 years; FEV1 53%pred, all current smokers), and 18 control subjects using 2 different validated quantitative and computer-assisted methods (repeated multiple point-to-point vs area by length ratio). Results: Reticular basement membrane thickness was higher in severe asthma compared with mild asthma and COPD (P =.0053). On the basis of receiver operating characteristic curves, RBM thickness was effective in differentiating severe asthma from other groups (sensitivity and specificity, 98% and 95%, respectively, above a threshold of 5 mu m vs control, 70% and 75% at 7 mu m vs mild, 83% and 68% at 6 mu m vs COPD). Conclusion: Increased RBM thickness was specifically associated with severe asthma, whereas surprisingly, COPD and mild asthma had similar remodeling features. Clinical implications: Reticular basement membrane thickness can be considered a hallmark of severe asthma.. asthma| copd| remodeling| basement membrane| roc|air-flow obstruction| subepithelial fibrosis| collagen deposition| bronchial-asthma| wall thickness| lung-function| expression| matrix-metalloproteinase-9| inflammation| transition.	JUN-2007	asthma| copd| remodeling| basement membrane| roc|air-flow obstruction| subepithelial fibrosis| collagen deposition| bronchial-asthma| wall thickness| lung-function| expression| matrix-metalloproteinase-9| inflammation| transition	Bourdin, A; Neveu, D; Vachier, I; Paganin, F; Godard, P; Chanez, P	Specificity of basement membrane thickening in severe asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; COPD; remodeling; basement membrane; ROC	AIR-FLOW OBSTRUCTION; SUBEPITHELIAL FIBROSIS; COLLAGEN DEPOSITION; BRONCHIAL-ASTHMA; WALL THICKNESS; LUNG-FUNCTION; EXPRESSION; MATRIX-METALLOPROTEINASE-9; INFLAMMATION; TRANSITION	Background: Reticular basement membrane (RBM) thickness is considered a hallmark for airway remodeling in airway diseases such as asthma. It is still unclear whether this measurement could be associated with disease severity or apply to chronic obstructive pulmonary disease (COPD). A wide range of results, at baseline or after therapeutic intervention, have been reported using different measurement methods. Objective: To determine whether increased RBM thickness could be associated specifically with severe asthma and in COPD in large samples. Methods: We blindly measured RBM thickness in endobronchial biopsies from 50 patients with severe asthma (mean age, 53 years; FEV1 66% predicted, inhaled steroids >= 1500 mu g and 20 mg daily dose of oral corticosteroids, lifelong nonsmokers), 50 untreated patients with mild asthma mean age, 33 years; FEV, 93%pred, lifelong nonsmokers), 50 patients with COPD (mean age, 57 years; FEV1 53%pred, all current smokers), and 18 control subjects using 2 different validated quantitative and computer-assisted methods (repeated multiple point-to-point vs area by length ratio). Results: Reticular basement membrane thickness was higher in severe asthma compared with mild asthma and COPD (P =.0053). On the basis of receiver operating characteristic curves, RBM thickness was effective in differentiating severe asthma from other groups (sensitivity and specificity, 98% and 95%, respectively, above a threshold of 5 mu m vs control, 70% and 75% at 7 mu m vs mild, 83% and 68% at 6 mu m vs COPD). Conclusion: Increased RBM thickness was specifically associated with severe asthma, whereas surprisingly, COPD and mild asthma had similar remodeling features. Clinical implications: Reticular basement membrane thickness can be considered a hallmark of severe asthma.	33	71	2007	8	10.1016/j.jaci.2007.01.055	Allergy; Immunology
Comparison of airway remodeling in acute, subacute, and chronic models of allergic airways disease. The relationship between airway inflammation and structural changes of airway remodeling, and their relative effects on airway function, are poorly understood. Remodeling is thought to result from chronic repetitive injury to the airway wall caused by airway inflammation; however, the mechanisms regulating remodeling changes have not been clearly defined. We examined the sequence of events in remodeling using three commonly used mouse models of allergic airways disease in which mice are exposed to nebulized ovalbumin for four consecutive days (acute), seven consecutive days (subacute), or three times a week for 6 wk (chronic). Surprisingly, we found that a very short period of exposure to ovalbumin was sufficient to elicit early changes of remodeling. Goblet cell hyperplasia and epithelial thickening were evident after just 4 d. In chronically challenged mice, these changes persisted and, in addition, subepithelial Collagen deposition was significantly increased. This Collagen deposition was associated with a failure to upregulate matrix metalloproteinase (MIMP)-2, in conjunction with increased transforming growth factor-beta and MMP-9 expression. The relationship between inflammation, remodeling changes, and airway hyperresponsiveness (AHR) were examined. The acute and subacute models exhibited marked airway inflammation, whereas the chronic model had very modest inflammation. Conversely, airway fibrosis was only evident in the chronic model. AHR was present in all three models; however, it was significantly higher in the chronic model compared with the acute (P < 0.05) and subacute (P < 0.05) models. These data demonstrate that both airway inflammation and airway fibrosis may contribute to AHR, with airway fibrosis leading to the greatest increases in AHR.. asthma| fibrosis| inflammation| mice|murine model| mouse model| experimental asthma| childhood asthma| bronchial-asthma| atopic asthma| animal-models| inflammation| fibrosis| expression.	MAY-2007	asthma| fibrosis| inflammation| mice|murine model| mouse model| experimental asthma| childhood asthma| bronchial-asthma| atopic asthma| animal-models| inflammation| fibrosis| expression	Locke, NR; Royce, SG; Wainewright, JS; Samuel, CS; Tang, ML	Comparison of airway remodeling in acute, subacute, and chronic models of allergic airways disease		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	asthma; fibrosis; inflammation; mice	MURINE MODEL; MOUSE MODEL; EXPERIMENTAL ASTHMA; CHILDHOOD ASTHMA; BRONCHIAL-ASTHMA; ATOPIC ASTHMA; ANIMAL-MODELS; INFLAMMATION; FIBROSIS; EXPRESSION	The relationship between airway inflammation and structural changes of airway remodeling, and their relative effects on airway function, are poorly understood. Remodeling is thought to result from chronic repetitive injury to the airway wall caused by airway inflammation; however, the mechanisms regulating remodeling changes have not been clearly defined. We examined the sequence of events in remodeling using three commonly used mouse models of allergic airways disease in which mice are exposed to nebulized ovalbumin for four consecutive days (acute), seven consecutive days (subacute), or three times a week for 6 wk (chronic). Surprisingly, we found that a very short period of exposure to ovalbumin was sufficient to elicit early changes of remodeling. Goblet cell hyperplasia and epithelial thickening were evident after just 4 d. In chronically challenged mice, these changes persisted and, in addition, subepithelial Collagen deposition was significantly increased. This Collagen deposition was associated with a failure to upregulate matrix metalloproteinase (MIMP)-2, in conjunction with increased transforming growth factor-beta and MMP-9 expression. The relationship between inflammation, remodeling changes, and airway hyperresponsiveness (AHR) were examined. The acute and subacute models exhibited marked airway inflammation, whereas the chronic model had very modest inflammation. Conversely, airway fibrosis was only evident in the chronic model. AHR was present in all three models; however, it was significantly higher in the chronic model compared with the acute (P < 0.05) and subacute (P < 0.05) models. These data demonstrate that both airway inflammation and airway fibrosis may contribute to AHR, with airway fibrosis leading to the greatest increases in AHR.	47	71	2007	8	10.1165/rcmb.2006-0083OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Surgical applications of cyanoacrylate adhesives: A review of toxicity. Cyanoacrylate (CA) and its homologues have a variety of medical and commercial applications as biological adhesives and sealants. Homologues of CA are being widely promoted in surgery as a tissue adhesive to replace traditional suturing techniques. Potential benefits of using CA adhesives include better cosmetic results, more rapid wound closure, and perhaps most significantly, the potential for significant reductions in percutaneous injuries from suture needles, which would in turn also reduce the risk of transmission of infectious diseases. Nevertheless, certain concerns have been raised regarding the potential toxicity of CA within patients, as well as among health professionals who are occupationally exposed when using CA compounds. Reported toxicity of CA in the workplace may result in dermatological, allergic and respiratory conditions. To help reduce the occupational burden, therefore, medical staff using CA adhesives should avoid direct contact with the compound and use appropriate personal protective measures at all times. Maintaining higher levels of humidity, optimizing room ventilation and using special air conditioning filters in surgical suites and operating theatres may also be useful in minimizing the exposure to volatile CA adhesives.. cyanoacrylate| medical| occupational allergy| occupational asthma| occupational skin disease| surgery| toxic effect|cell-culture method| tissue adhesive| isobutyl cyanoacrylate| carotid-artery| cyto-toxicity| surgery| glue| 2-cyanoacrylate| cytotoxicity| management.	APR-2007	cyanoacrylate| medical| occupational allergy| occupational asthma| occupational skin disease| surgery| toxic effect|cell-culture method| tissue adhesive| isobutyl cyanoacrylate| carotid-artery| cyto-toxicity| surgery| glue| 2-cyanoacrylate| cytotoxicity| management	Leggat, PA; Smith, DR; Kedjarune, U	Surgical applications of cyanoacrylate adhesives: A review of toxicity		ANZ JOURNAL OF SURGERY	cyanoacrylate; medical; occupational allergy; occupational asthma; occupational skin disease; surgery; toxic effect	CELL-CULTURE METHOD; TISSUE ADHESIVE; ISOBUTYL CYANOACRYLATE; CAROTID-ARTERY; CYTO-TOXICITY; SURGERY; GLUE; 2-CYANOACRYLATE; CYTOTOXICITY; MANAGEMENT	Cyanoacrylate (CA) and its homologues have a variety of medical and commercial applications as biological adhesives and sealants. Homologues of CA are being widely promoted in surgery as a tissue adhesive to replace traditional suturing techniques. Potential benefits of using CA adhesives include better cosmetic results, more rapid wound closure, and perhaps most significantly, the potential for significant reductions in percutaneous injuries from suture needles, which would in turn also reduce the risk of transmission of infectious diseases. Nevertheless, certain concerns have been raised regarding the potential toxicity of CA within patients, as well as among health professionals who are occupationally exposed when using CA compounds. Reported toxicity of CA in the workplace may result in dermatological, allergic and respiratory conditions. To help reduce the occupational burden, therefore, medical staff using CA adhesives should avoid direct contact with the compound and use appropriate personal protective measures at all times. Maintaining higher levels of humidity, optimizing room ventilation and using special air conditioning filters in surgical suites and operating theatres may also be useful in minimizing the exposure to volatile CA adhesives.	56	71	2007	5	10.1111/j.1445-2197.2007.04020.x	Surgery
Role of small airways in asthma: Investigation using high-resolution computed tomography. Background: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. Objective: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. Methods: Both lungs were scanned at full-inspiratory and fullexpiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < -960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. Results: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV1/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV1/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV1 and FEV1/FVC) and peripheral airflow obstruction. Conclusion: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. Clinical implications: Small airways are an important therapeutic target in asthma.. asthma| small airways| high-resolution computed tomography| lung density| airway responsiveness| airway inflammation| airway remodeling| air trapping|obstructive pulmonary-disease| low-attenuation areas| ct lung densitometry| wall thickness| sputum induction| fatal asthma| distal lung| inflammation| emphysema| hydrofluoroalkane.	NOV-2006	asthma| small airways| high-resolution computed tomography| lung density| airway responsiveness| airway inflammation| airway remodeling| air trapping|obstructive pulmonary-disease| low-attenuation areas| ct lung densitometry| wall thickness| sputum induction| fatal asthma| distal lung| inflammation| emphysema| hydrofluoroalkane	Ueda, T; Niimi, A; Matsumoto, H; Takemura, M; Hirai, T; Yamaguchi, M; Matsuoka, H; Jinnai, M; Muro, S; Chin, K; Mishima, M	Role of small airways in asthma: Investigation using high-resolution computed tomography		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; small airways; high-resolution computed tomography; lung density; airway responsiveness; airway inflammation; airway remodeling; air trapping	OBSTRUCTIVE PULMONARY-DISEASE; LOW-ATTENUATION AREAS; CT LUNG DENSITOMETRY; WALL THICKNESS; SPUTUM INDUCTION; FATAL ASTHMA; DISTAL LUNG; INFLAMMATION; EMPHYSEMA; HYDROFLUOROALKANE	Background: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. Objective: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. Methods: Both lungs were scanned at full-inspiratory and fullexpiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < -960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. Results: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV1/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV1/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV1 and FEV1/FVC) and peripheral airflow obstruction. Conclusion: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. Clinical implications: Small airways are an important therapeutic target in asthma.	52	71	2006	7	10.1016/j.jaci.2006.07.032	Allergy; Immunology
Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study. Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.. sublingual immunotherapy| house dust mite| asthma| igg4|house-dust mite| allergen-specific immunotherapy| controlled-trial| antibody-levels| efficacy| rhinitis| extract| safety| slit| igg.	SEP-2006	sublingual immunotherapy| house dust mite| asthma| igg4|house-dust mite| allergen-specific immunotherapy| controlled-trial| antibody-levels| efficacy| rhinitis| extract| safety| slit| igg	Lue, KH; Lin, YH; Sun, HL; Lu, KH; Hsieh, JC; Chou, MC	Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double-blind, randomized, placebo-controlled study		PEDIATRIC ALLERGY AND IMMUNOLOGY	sublingual immunotherapy; house dust mite; asthma; IgG4	HOUSE-DUST MITE; ALLERGEN-SPECIFIC IMMUNOTHERAPY; CONTROLLED-TRIAL; ANTIBODY-LEVELS; EFFICACY; RHINITIS; EXTRACT; SAFETY; SLIT; IGG	Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.	23	71	2006	8	10.1111/j.1399-3038.2006.00443.x	Allergy; Immunology; Pediatrics
Allergic airway inflammation inhibits pulmonary antibacterial host defense. The innate immune system of the lung is a multicomponent host defense system and in addition has an instructing role in regulating the quality and quantity of the adaptive immune response. When the interaction between innate and adaptive immunity is disturbed, pathological conditions such as asthma can develop. It was the aim of the study to investigate the effect of the allergic inflammation of the lung on the innate host defense during bacterial infection. Human bronchial epithelial cells were preinculvated with Th2 cytokines and infected with Pseudomonas aeruginosa. The effect of the Th2 cytokines on the mRNA levels of antimicrobial peptides and the antimicrobial activity of HBEC was determined. To investigate the influence of an allergic inflammation on pulmonary host defense in vivo, mice sensitized and challenged with OVA were infected with P. aeruginosa, and the number of viable bacteria in the lungs was determined together with markers of inflammation like cytokines and antimicrobial peptides. Exposure of airway epithelial cells to Th2 cytokines resulted in a significantly decreased antimicrobial activity of the cells and in suppressed mRNA levels of the antimicrobial peptide human beta-defensin 2. Furthermore, mice with allergic airway inflammation had significantly more viable bacteria in their lungs after infection. This was consistent with reduced levels of proinflammatory cytokines and of the antimicrobial peptide cathelin-related antimicrobial peptide. These results show that an allergic airway inflammation suppresses the innate antimicrobial host defense. The adaptive immune system modulates the functions of the pulmonary innate immune system.. innate immune-response| antimicrobial peptides| atopic-dermatitis| lung inflammation| risk-factors| asthma| pneumonia| polarization| pathogenesis| epithelium.	AUG 1-2006	innate immune-response| antimicrobial peptides| atopic-dermatitis| lung inflammation| risk-factors| asthma| pneumonia| polarization| pathogenesis| epithelium	Beisswenger, C; Kandler, K; Hess, C; Garn, H; Felgentreff, K; Wegmann, M; Renz, H; Vogelmeier, C; Bals, R	Allergic airway inflammation inhibits pulmonary antibacterial host defense		JOURNAL OF IMMUNOLOGY		INNATE IMMUNE-RESPONSE; ANTIMICROBIAL PEPTIDES; ATOPIC-DERMATITIS; LUNG INFLAMMATION; RISK-FACTORS; ASTHMA; PNEUMONIA; POLARIZATION; PATHOGENESIS; EPITHELIUM	The innate immune system of the lung is a multicomponent host defense system and in addition has an instructing role in regulating the quality and quantity of the adaptive immune response. When the interaction between innate and adaptive immunity is disturbed, pathological conditions such as asthma can develop. It was the aim of the study to investigate the effect of the allergic inflammation of the lung on the innate host defense during bacterial infection. Human bronchial epithelial cells were preinculvated with Th2 cytokines and infected with Pseudomonas aeruginosa. The effect of the Th2 cytokines on the mRNA levels of antimicrobial peptides and the antimicrobial activity of HBEC was determined. To investigate the influence of an allergic inflammation on pulmonary host defense in vivo, mice sensitized and challenged with OVA were infected with P. aeruginosa, and the number of viable bacteria in the lungs was determined together with markers of inflammation like cytokines and antimicrobial peptides. Exposure of airway epithelial cells to Th2 cytokines resulted in a significantly decreased antimicrobial activity of the cells and in suppressed mRNA levels of the antimicrobial peptide human beta-defensin 2. Furthermore, mice with allergic airway inflammation had significantly more viable bacteria in their lungs after infection. This was consistent with reduced levels of proinflammatory cytokines and of the antimicrobial peptide cathelin-related antimicrobial peptide. These results show that an allergic airway inflammation suppresses the innate antimicrobial host defense. The adaptive immune system modulates the functions of the pulmonary innate immune system.	24	71	2006	5		Immunology
Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation. Background: Epidemiologic studies show that exposure to ambient particulate matter leads to asthma exacerbation. Diesel exhaust particles (DEPs), a model pollutant, act as an adjuvant for allergic sensitization. Increasing evidence shows that this effect could be mediated by an effect on dendritic cells (DCs). Objective: Our aim was to elucidate the mechanism by which pro-oxidative DEP chemicals change DC function so that these antigen-presenting cells strengthen the immune response to an experimental allergen. Methods: We exposed murine bone marrow-derived DCs and a homogeneous myeloid DC line, BC1, to DEPs and organic extracts made from these particles to determine how the induction of oxidative stress affects cellular maturation, cytokine production, and activation of antigen-specific T cells. Results: DEP extracts induced oxidative stress in DCs. This change in redox equilibrium interfered in the ability of Toll-like receptor agonists to induce the expression of maturation receptors (eg, CD86, CD54, and I-A(d)) and IL-12 production. This perturbation of DC function was accompanied by decreased IFN-gamma and increased IL-10 induction in antigen-specific T cells. The molecular basis for the perturbation of DC function is the activation of a nuclear factor-erythroid 2 (NF-E2)-related factor 2-mediated signaling pathway that suppresses IL-12 production. NF-E2-related factor 2 deficiency abrogates the perturbation of DC function by DEPs. Conclusion: These data provide the first report that prooxidative DEP chemicals can interfere in T(H)1-promoting response pathways in a homogeneous DC population and provide a novel explanation for the adjuvant effect of DEPs on allergic inflammation.. dendritic cells| t(h)1/t(h)2 cells| lps| cell differentiation|nf-kappa-b| antigen-presenting cells| airway inflammation| epithelial-cells| deposition patterns| heme oxygenase-1| inhaled antigen| th2 responses| murine model| activation.	AUG-2006	dendritic cells| t(h)1/t(h)2 cells| lps| cell differentiation|nf-kappa-b| antigen-presenting cells| airway inflammation| epithelial-cells| deposition patterns| heme oxygenase-1| inhaled antigen| th2 responses| murine model| activation	Chan, RCF; Wang, MY; Li, N; Yanagawa, Y; Onoe, K; Lee, JJ; Nel, AE	Pro-oxidative diesel exhaust particle chemicals inhibit LPS-induced dendritic cell responses involved in T-helper differentiation		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	dendritic cells; T(H)1/T(H)2 cells; LPS; cell differentiation	NF-KAPPA-B; ANTIGEN-PRESENTING CELLS; AIRWAY INFLAMMATION; EPITHELIAL-CELLS; DEPOSITION PATTERNS; HEME OXYGENASE-1; INHALED ANTIGEN; TH2 RESPONSES; MURINE MODEL; ACTIVATION	Background: Epidemiologic studies show that exposure to ambient particulate matter leads to asthma exacerbation. Diesel exhaust particles (DEPs), a model pollutant, act as an adjuvant for allergic sensitization. Increasing evidence shows that this effect could be mediated by an effect on dendritic cells (DCs). Objective: Our aim was to elucidate the mechanism by which pro-oxidative DEP chemicals change DC function so that these antigen-presenting cells strengthen the immune response to an experimental allergen. Methods: We exposed murine bone marrow-derived DCs and a homogeneous myeloid DC line, BC1, to DEPs and organic extracts made from these particles to determine how the induction of oxidative stress affects cellular maturation, cytokine production, and activation of antigen-specific T cells. Results: DEP extracts induced oxidative stress in DCs. This change in redox equilibrium interfered in the ability of Toll-like receptor agonists to induce the expression of maturation receptors (eg, CD86, CD54, and I-A(d)) and IL-12 production. This perturbation of DC function was accompanied by decreased IFN-gamma and increased IL-10 induction in antigen-specific T cells. The molecular basis for the perturbation of DC function is the activation of a nuclear factor-erythroid 2 (NF-E2)-related factor 2-mediated signaling pathway that suppresses IL-12 production. NF-E2-related factor 2 deficiency abrogates the perturbation of DC function by DEPs. Conclusion: These data provide the first report that prooxidative DEP chemicals can interfere in T(H)1-promoting response pathways in a homogeneous DC population and provide a novel explanation for the adjuvant effect of DEPs on allergic inflammation.	45	71	2006	11	10.1016/j.jaci.2006.06.006	Allergy; Immunology
A land use regression model for predicting ambient concentrations of nitrogen dioxide in Hamilton, Ontario, Canada. This paper reports on the development of a land use regression (LUR) model for predicting the intraurban variation of traffic-related air pollution in Hamilton, Ontario, Canada, an industrial city at the western end of Lake Ontario. Although land use regression has been increasingly used to characterize exposure gradients within cities, research to date has yet to test whether this method can produce reliable estimates in an industrialized location. Ambient concentrations of nitrogen dioxide (NO,) were measured for a 2-week period in October 2002 at > 100 locations across the city and subsequently at 30 of these locations in May 2004 to assess seasonal effects. Predictor variables were derived for land use types, transportation, demography, and, physical geography using geographic information systems. The LUR model explained 76% of the variation in NO2. Traffic density, proximity to a highway, and industrial land use were all positively correlated with NO, concentrations, whereas open land use and distance from the lake were negatively correlated with NO2. Locations downwind of a major highway resulted in higher NO2 levels. Cross-validation of the results confirmed model stability Over different seasons. Our findings demonstrate that land use regression can effectively predict NO, variation at the intraurban scale in an industrial setting. Models predicting exposure within smaller areas may lead to improved detection of health effects in epidemiologic studies.. particulate air-pollution| exposure assessment| personal exposure| environmental justice| spatial variability| childhood asthma| major highway| urban area| children| mortality.	AUG-2006	particulate air-pollution| exposure assessment| personal exposure| environmental justice| spatial variability| childhood asthma| major highway| urban area| children| mortality	Sahsuvaroglu, T; Arain, A; Kanaroglou, P; Finkelstein, N; Newbold, B; Jerrett, M; Beckerman, B; Brook, J; Finkelstein, M; Gilbert, NL	A land use regression model for predicting ambient concentrations of nitrogen dioxide in Hamilton, Ontario, Canada		JOURNAL OF THE AIR & WASTE MANAGEMENT ASSOCIATION		PARTICULATE AIR-POLLUTION; EXPOSURE ASSESSMENT; PERSONAL EXPOSURE; ENVIRONMENTAL JUSTICE; SPATIAL VARIABILITY; CHILDHOOD ASTHMA; MAJOR HIGHWAY; URBAN AREA; CHILDREN; MORTALITY	This paper reports on the development of a land use regression (LUR) model for predicting the intraurban variation of traffic-related air pollution in Hamilton, Ontario, Canada, an industrial city at the western end of Lake Ontario. Although land use regression has been increasingly used to characterize exposure gradients within cities, research to date has yet to test whether this method can produce reliable estimates in an industrialized location. Ambient concentrations of nitrogen dioxide (NO,) were measured for a 2-week period in October 2002 at > 100 locations across the city and subsequently at 30 of these locations in May 2004 to assess seasonal effects. Predictor variables were derived for land use types, transportation, demography, and, physical geography using geographic information systems. The LUR model explained 76% of the variation in NO2. Traffic density, proximity to a highway, and industrial land use were all positively correlated with NO, concentrations, whereas open land use and distance from the lake were negatively correlated with NO2. Locations downwind of a major highway resulted in higher NO2 levels. Cross-validation of the results confirmed model stability Over different seasons. Our findings demonstrate that land use regression can effectively predict NO, variation at the intraurban scale in an industrial setting. Models predicting exposure within smaller areas may lead to improved detection of health effects in epidemiologic studies.	51	71	2006	11		Engineering; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
"Chronic cough due to nonasthmatic eosinophilic bronchitis - ACCP evidence-based clinical practice guidelines. Objectives: Nonasthmatic eosinophilic bronchitis is a newly recognized cause of chronic cough. Our objective was to review the pathogenesis, natural history, diagnosis, and treatment of this condition. Methods: The current literature was reviewed using an Ovid MEDLINE and PubMed literature review for all studies published in the English language from 1963 to December 2004 using the medical subject heading term ""eosinophilic bronchitis."" Results: Nonasthmatic eosinophilic bronchitis is a common cause of chronic cough. it is characterized by the presence of eosinophilic airway inflammation, similar to that seen in asthma. However, in contrast to asthma, nonasthmatic eosinophilic bronchitis is not associated with variable airflow limitation or airway hyperresponsiveness. The differences in functional association are related to differences in the localization of mast cells within the airway wall, with airway smooth muscle infiltration occurring in patients with asthma, and epithelial infiltration in patients with nonasthmatic eosinophilic bronchitis. Diagnosis is made by the confirmation of eosinophilic airway inflammation usually with induced sputum analysis after the exclusion of other causes for chronic cough on clinical, radiologic, and lung function assessment. The cough usually responds well to treatment with inhaled corticosteroids. The dose and duration of treatment differ between patients. The condition can be transient, episodic, or persistent unless treated, and occasionally patients may require long-term prednisone treatment. Conclusions: Further study of this condition may improve our understanding of airway inflammation and airway responsiveness, leading to novel targets for therapeutic agents for the treatment of both asthma and nonasthmatic eosinophilic bronchitis.. airway smooth muscle| asthma| cough| eosinophilic bronchitis| eosinophils| mast cells|chronic nonproductive cough| air-flow obstruction| induced sputum| variant asthma| atopic cough| inflammation| frequency| spectrum| therapy| disease."	JAN-2006	airway smooth muscle| asthma| cough| eosinophilic bronchitis| eosinophils| mast cells|chronic nonproductive cough| air-flow obstruction| induced sputum| variant asthma| atopic cough| inflammation| frequency| spectrum| therapy| disease	Brightling, CE	Chronic cough due to nonasthmatic eosinophilic bronchitis - ACCP evidence-based clinical practice guidelines		CHEST	airway smooth muscle; asthma; cough; eosinophilic bronchitis; eosinophils; mast cells	CHRONIC NONPRODUCTIVE COUGH; AIR-FLOW OBSTRUCTION; INDUCED SPUTUM; VARIANT ASTHMA; ATOPIC COUGH; INFLAMMATION; FREQUENCY; SPECTRUM; THERAPY; DISEASE	"Objectives: Nonasthmatic eosinophilic bronchitis is a newly recognized cause of chronic cough. Our objective was to review the pathogenesis, natural history, diagnosis, and treatment of this condition. Methods: The current literature was reviewed using an Ovid MEDLINE and PubMed literature review for all studies published in the English language from 1963 to December 2004 using the medical subject heading term ""eosinophilic bronchitis."" Results: Nonasthmatic eosinophilic bronchitis is a common cause of chronic cough. it is characterized by the presence of eosinophilic airway inflammation, similar to that seen in asthma. However, in contrast to asthma, nonasthmatic eosinophilic bronchitis is not associated with variable airflow limitation or airway hyperresponsiveness. The differences in functional association are related to differences in the localization of mast cells within the airway wall, with airway smooth muscle infiltration occurring in patients with asthma, and epithelial infiltration in patients with nonasthmatic eosinophilic bronchitis. Diagnosis is made by the confirmation of eosinophilic airway inflammation usually with induced sputum analysis after the exclusion of other causes for chronic cough on clinical, radiologic, and lung function assessment. The cough usually responds well to treatment with inhaled corticosteroids. The dose and duration of treatment differ between patients. The condition can be transient, episodic, or persistent unless treated, and occasionally patients may require long-term prednisone treatment. Conclusions: Further study of this condition may improve our understanding of airway inflammation and airway responsiveness, leading to novel targets for therapeutic agents for the treatment of both asthma and nonasthmatic eosinophilic bronchitis."	31	71	2006	6	10.1378/chest.129.1_suppl.116S	General & Internal Medicine; Respiratory System
IgE-mediated allergen presentation and blocking antibodies: Regulation of T-Cell activation in allergy. it is well established that both the production of IgE by B lymphocytes and the maturation and recruitment of eosinophils in late-phase reactions are dependent on the activation of allergen-specific type-2 T-helper cells. What is less well known is the fact that efficient activation of allergen-specific T cells upon low-dose exposure to allergens is critically dependent on IgE-mediated or -facilitated allergen presentation. In fact, changes in the level of IgE-mediated allergen presentation may account for many of the immunological effects described for specific immunotherapy or anti-IgE treatment. This review aims to summarize the current knowledge, and will discuss the clinical relevance of blocking IgG antibodies induced by specific immunotherapy and anti-IgE monoclonal antibodies that both interfere with IgE-mediated allergen presentation. Copyright (c) 2006 S. Karger AG, Basel.. allergen presentation| blocking antibodies| ige immunotherapy|fc-epsilon-ri| grass-pollen immunotherapy| low-affinity receptor| epidermal langerhans cells| basophil histamine-release| late asthmatic response| antigen-specific ige| hay-fever patients| in-vivo| serum-ige.	2006	allergen presentation| blocking antibodies| ige immunotherapy|fc-epsilon-ri| grass-pollen immunotherapy| low-affinity receptor| epidermal langerhans cells| basophil histamine-release| late asthmatic response| antigen-specific ige| hay-fever patients| in-vivo| serum-ige	van Neerven, RJ; Knoll, EF; Ejrnaes, A; Wurtzen, PA	IgE-mediated allergen presentation and blocking antibodies: Regulation of T-Cell activation in allergy		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	allergen presentation; blocking antibodies; IgE immunotherapy	FC-EPSILON-RI; GRASS-POLLEN IMMUNOTHERAPY; LOW-AFFINITY RECEPTOR; EPIDERMAL LANGERHANS CELLS; BASOPHIL HISTAMINE-RELEASE; LATE ASTHMATIC RESPONSE; ANTIGEN-SPECIFIC IGE; HAY-FEVER PATIENTS; IN-VIVO; SERUM-IGE	it is well established that both the production of IgE by B lymphocytes and the maturation and recruitment of eosinophils in late-phase reactions are dependent on the activation of allergen-specific type-2 T-helper cells. What is less well known is the fact that efficient activation of allergen-specific T cells upon low-dose exposure to allergens is critically dependent on IgE-mediated or -facilitated allergen presentation. In fact, changes in the level of IgE-mediated allergen presentation may account for many of the immunological effects described for specific immunotherapy or anti-IgE treatment. This review aims to summarize the current knowledge, and will discuss the clinical relevance of blocking IgG antibodies induced by specific immunotherapy and anti-IgE monoclonal antibodies that both interfere with IgE-mediated allergen presentation. Copyright (c) 2006 S. Karger AG, Basel.	124	71	2006	11	10.1159/000094714	Allergy; Immunology
Detection of airborne Stachybotrys chartarum macrocyclic trichothecene mycotoxins in the indoor environment. The existence of airborne mycotoxins in mold-contaminated buildings has long been hypothesized to be a potential occupant health risk. However, little work has been done to demonstrate the presence of these compounds in such environments. The presence of airborne macrocyclic trichothecene mycotoxins in indoor environments with known Stachybotrys chartarum contamination was therefore investigated. In seven buildings, air was collected using a high-volume liquid impaction bioaerosol sampler (SpinCon PAS 450-10) under static or disturbed conditions. An additional building was sampled using an Andersen GPS-1 PUF sampler modified to separate and collect particulates smaller than conidia. Four control buildings (i.e., no detectable S. chartarum growth or history of water damage) and outdoor air were also tested. Samples were analyzed using a macrocyclic trichothecene-specific enzyme-linked immunosorbent assay (ELISA). ELISA specificity was tested using phosphate-buffered saline extracts of the fungal genera Aspergillus, Chaetomium, Cladosporium, Fusarium, Memnoniella, Penicillium, Rhizopus, and Trichoderma, five Stachybotrys strains, and the indoor air allergens Can f 1, Der p 1, and Fel d 1. For test buildings, the results showed that detectable toxin concentrations increased with the sampling time and short periods of air disturbance. Trichothecene values ranged from < 10 to > 1,300 pg/m(3) of sampled air. The control environments demonstrated statistically significantly (P < 0.001) lower levels of airborne trichothecenes. ELISA specificity experiments demonstrated a high specificity for the trichothecene-producing strain of S. chartarum. Our data indicate that airborne macrocyclic trichothecenes can exist in Stachybotrys-contaminated buildings, and this should be taken into consideration in future indoor air quality investigations.. sick building syndrome| pulmonary hemosiderosis| satratoxin-g| contamination| exposure| fungi| mice| atra| anguidine| samplers.	NOV-2005	sick building syndrome| pulmonary hemosiderosis| satratoxin-g| contamination| exposure| fungi| mice| atra| anguidine| samplers	Brasel, TL; Martin, JM; Carriker, CG; Wilson, SC; Straus, DC	Detection of airborne Stachybotrys chartarum macrocyclic trichothecene mycotoxins in the indoor environment		APPLIED AND ENVIRONMENTAL MICROBIOLOGY		SICK BUILDING SYNDROME; PULMONARY HEMOSIDEROSIS; SATRATOXIN-G; CONTAMINATION; EXPOSURE; FUNGI; MICE; ATRA; ANGUIDINE; SAMPLERS	The existence of airborne mycotoxins in mold-contaminated buildings has long been hypothesized to be a potential occupant health risk. However, little work has been done to demonstrate the presence of these compounds in such environments. The presence of airborne macrocyclic trichothecene mycotoxins in indoor environments with known Stachybotrys chartarum contamination was therefore investigated. In seven buildings, air was collected using a high-volume liquid impaction bioaerosol sampler (SpinCon PAS 450-10) under static or disturbed conditions. An additional building was sampled using an Andersen GPS-1 PUF sampler modified to separate and collect particulates smaller than conidia. Four control buildings (i.e., no detectable S. chartarum growth or history of water damage) and outdoor air were also tested. Samples were analyzed using a macrocyclic trichothecene-specific enzyme-linked immunosorbent assay (ELISA). ELISA specificity was tested using phosphate-buffered saline extracts of the fungal genera Aspergillus, Chaetomium, Cladosporium, Fusarium, Memnoniella, Penicillium, Rhizopus, and Trichoderma, five Stachybotrys strains, and the indoor air allergens Can f 1, Der p 1, and Fel d 1. For test buildings, the results showed that detectable toxin concentrations increased with the sampling time and short periods of air disturbance. Trichothecene values ranged from < 10 to > 1,300 pg/m(3) of sampled air. The control environments demonstrated statistically significantly (P < 0.001) lower levels of airborne trichothecenes. ELISA specificity experiments demonstrated a high specificity for the trichothecene-producing strain of S. chartarum. Our data indicate that airborne macrocyclic trichothecenes can exist in Stachybotrys-contaminated buildings, and this should be taken into consideration in future indoor air quality investigations.	50	71	2005	13	10.1128/AEM.71.11.7376-7388.2005	Biotechnology & Applied Microbiology; Microbiology
Culturable airborne fungi in outdoor environments in Beijing, China. Airborne fungi are being proposed as a cause of adverse health effects. They may adversely affect human health through allergy, infection, and toxicity. Moreover, they have a great influence on urban air quality in Beijing. In this study, a systematical survey on the culturable airborne fungi was carried out for I year in Beijing urban area. Fungal samples were collected for 3 min, three times each day, and continued for three consecutive days of each month with FA-1 sampler from three sampling sites. Results showed that the culturable fungal concentrations ranged from 24 CFU (Colony forming units) /m(3) to 13960 CFU/m(3), and the mean and median was 1165 CFU/m(3) and 710 CFU/m(3), respectively. Fungal concentrations in the greener area around the Research Center for Eco-Environmental Sciences (RCEES) and Beijing Botanical Garden (BBG) were significantly higher than in the densely urban and highly trafficked area of Xizhimen (XZM) (***P < 0.001), but no significant difference was found between RCEES and BBG (P > 0.05). The variation of fungal concentrations in different seasons was significant in RCEES and BBG, where the concentrations were higher in Summer and Autumn, and lower in Spring and Winter. However, there were no significant differences in fungal concentrations between the Spring and the Winter for three sampling sites (P > 0.05). Fourteen genera, including 40 species of culturable fungi, were identified in this study. Penicillium, with the most abundant species, which comprised more than 50% of the total isolated fungal species. Cladosporium were the most dominant fungal group, and contributed to more than one third of the total fungal concentration, followed by non-sporing isolates, Alternaria, Pencillium and Asperigillus. The concentration percentage of Cladosporium was significantly higher in RCEES than in XZM (*P < 0.05), and the concentration percentages of Penicillium (**P < 0.01) and Aspergillus (*P < 0.05) were higher in XZM than in RCEES and in BBG. For other groups' concentration percentages, no significant differences were observed among the sampling sites.. culturable airborne fungi| bioaerosol| aerobiology| size distribution pattern|control children| indoor air| bioaerosols| residences| buildings| allergens| microbes| stations| asthma.	NOV 1-2005	culturable airborne fungi| bioaerosol| aerobiology| size distribution pattern|control children| indoor air| bioaerosols| residences| buildings| allergens| microbes| stations| asthma	Fang, ZG; Ouyang, ZY; Hu, LF; Wang, XK; Zheng, H; Lin, XQ	Culturable airborne fungi in outdoor environments in Beijing, China		SCIENCE OF THE TOTAL ENVIRONMENT	culturable airborne fungi; bioaerosol; aerobiology; size distribution pattern	CONTROL CHILDREN; INDOOR AIR; BIOAEROSOLS; RESIDENCES; BUILDINGS; ALLERGENS; MICROBES; STATIONS; ASTHMA	Airborne fungi are being proposed as a cause of adverse health effects. They may adversely affect human health through allergy, infection, and toxicity. Moreover, they have a great influence on urban air quality in Beijing. In this study, a systematical survey on the culturable airborne fungi was carried out for I year in Beijing urban area. Fungal samples were collected for 3 min, three times each day, and continued for three consecutive days of each month with FA-1 sampler from three sampling sites. Results showed that the culturable fungal concentrations ranged from 24 CFU (Colony forming units) /m(3) to 13960 CFU/m(3), and the mean and median was 1165 CFU/m(3) and 710 CFU/m(3), respectively. Fungal concentrations in the greener area around the Research Center for Eco-Environmental Sciences (RCEES) and Beijing Botanical Garden (BBG) were significantly higher than in the densely urban and highly trafficked area of Xizhimen (XZM) (***P < 0.001), but no significant difference was found between RCEES and BBG (P > 0.05). The variation of fungal concentrations in different seasons was significant in RCEES and BBG, where the concentrations were higher in Summer and Autumn, and lower in Spring and Winter. However, there were no significant differences in fungal concentrations between the Spring and the Winter for three sampling sites (P > 0.05). Fourteen genera, including 40 species of culturable fungi, were identified in this study. Penicillium, with the most abundant species, which comprised more than 50% of the total isolated fungal species. Cladosporium were the most dominant fungal group, and contributed to more than one third of the total fungal concentration, followed by non-sporing isolates, Alternaria, Pencillium and Asperigillus. The concentration percentage of Cladosporium was significantly higher in RCEES than in XZM (*P < 0.05), and the concentration percentages of Penicillium (**P < 0.01) and Aspergillus (*P < 0.05) were higher in XZM than in RCEES and in BBG. For other groups' concentration percentages, no significant differences were observed among the sampling sites.	41	71	2005	12	10.1016/j.scitotenv.2005.01.032	Environmental Sciences & Ecology
Risk factors for asthma and atopy. Purpose of review The aim of this article is to provide information on risk factors associated with the development of atopy and asthma in childhood. Recent findings Several gene polymorphisms have been associated with susceptibility to asthma and allergy; complex gene-environmental interactions, however, appear to play a key role in the development of the disease. Early life sensitization to aeroallergens, presence of atopic dermatitis or allergic rhinitis, maternal smoking during pregnancy and children's environmental exposure to tobacco smoke, lower respiratory tract infections with respiratory syncytial virus and potentially with other viruses including rhinovirus and metapneumovirus, exposure to air pollutants, several perinatal factors other than maternal smoking, are among factors associated with an increased risk for development of chronic asthma. Summary The prevalence of asthma and allergic diseases is increasing progressively. Those who are involved in the care of young children should be prepared to recognize risk factors for development of these diseases and to appreciate the role of gene-environment interactions. Preventive measures established at an early age may modify the natural history of asthma and other allergic diseases.. allergen sensitization| asthma| gene-environment interactions| respiratory viral infections| risk factors for asthma|childhood asthma| sex-differences| bronchial hyperresponsiveness| allergic rhinitis| indoor allergens| viral-infections| maternal smoking| immunoglobulin-e| birth cohort| breast-milk.	APR-2005	allergen sensitization| asthma| gene-environment interactions| respiratory viral infections| risk factors for asthma|childhood asthma| sex-differences| bronchial hyperresponsiveness| allergic rhinitis| indoor allergens| viral-infections| maternal smoking| immunoglobulin-e| birth cohort| breast-milk	Arruda, LK; Sole, D; Baena-Cagnani, CE; Naspitz, CK	Risk factors for asthma and atopy		CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY	allergen sensitization; asthma; gene-environment interactions; respiratory viral infections; risk factors for asthma	CHILDHOOD ASTHMA; SEX-DIFFERENCES; BRONCHIAL HYPERRESPONSIVENESS; ALLERGIC RHINITIS; INDOOR ALLERGENS; VIRAL-INFECTIONS; MATERNAL SMOKING; IMMUNOGLOBULIN-E; BIRTH COHORT; BREAST-MILK	Purpose of review The aim of this article is to provide information on risk factors associated with the development of atopy and asthma in childhood. Recent findings Several gene polymorphisms have been associated with susceptibility to asthma and allergy; complex gene-environmental interactions, however, appear to play a key role in the development of the disease. Early life sensitization to aeroallergens, presence of atopic dermatitis or allergic rhinitis, maternal smoking during pregnancy and children's environmental exposure to tobacco smoke, lower respiratory tract infections with respiratory syncytial virus and potentially with other viruses including rhinovirus and metapneumovirus, exposure to air pollutants, several perinatal factors other than maternal smoking, are among factors associated with an increased risk for development of chronic asthma. Summary The prevalence of asthma and allergic diseases is increasing progressively. Those who are involved in the care of young children should be prepared to recognize risk factors for development of these diseases and to appreciate the role of gene-environment interactions. Preventive measures established at an early age may modify the natural history of asthma and other allergic diseases.	81	71	2005	7	10.1097/01.all.0000162308.89857.6c	Allergy; Immunology
The World Trade Center residents' respiratory health study: New-onset respiratory symptoms and pulmonary function. The destruction of the World Trade Center (WTC) on 11 September 2001 in New York City resulted in the massive release of pulverized dust and combustion products. The dust and smoke settled in the surrounding area, which encompassed a large residential community. We hypothesized that previously normal residents in the community surrounding the former WTC would have an increased incidence of persistent respiratory symptoms and abnormalities in screening spirometry. A hybrid cross-sectional and retrospective cohort study using a symptom-based questionnaire and onsite screening spirometry in residents in an exposed area and in a control area was performed 12 +/- 4 months after the collapse. Surveys were analyzed from 2,812 residents. New-onset respiratory symptoms were described by 55.8% of residents in the exposed area, compared with 20.1% in the control area after the event. Persistent new-onset symptoms were identified in 26.4 versus 7.5% of residents in the exposed area versus control area, respectively. No differences in screening spirometry between the groups were detected. A small pilot study suggested the possibility of an increase in bronchial hyperresponsiveness in exposed participants with persistent symptoms. The data demonstrate an increased rate of new-onset and persistent respiratory health effects in residents near the former WTC compared with a control population.. asthma| environmental| disasters| environmental hazards| reactive airways dysfunction| world trade center|airways dysfunction syndrome| fine particulate matter| persistent asthma| lower manhattan| syndrome rads| questionnaire| firefighters| september-11| guidelines| validity.	APR-2005	asthma| environmental| disasters| environmental hazards| reactive airways dysfunction| world trade center|airways dysfunction syndrome| fine particulate matter| persistent asthma| lower manhattan| syndrome rads| questionnaire| firefighters| september-11| guidelines| validity	Reibman, J; Lin, S; Hwang, SAA; Gulati, M; Bowers, JA; Rogers, L; Berger, KI; Hoerning, A; Gomez, M; Fitzgerald, EF	The World Trade Center residents' respiratory health study: New-onset respiratory symptoms and pulmonary function		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; environmental; disasters; environmental hazards; reactive airways dysfunction; World Trade Center	AIRWAYS DYSFUNCTION SYNDROME; FINE PARTICULATE MATTER; PERSISTENT ASTHMA; LOWER MANHATTAN; SYNDROME RADS; QUESTIONNAIRE; FIREFIGHTERS; SEPTEMBER-11; GUIDELINES; VALIDITY	The destruction of the World Trade Center (WTC) on 11 September 2001 in New York City resulted in the massive release of pulverized dust and combustion products. The dust and smoke settled in the surrounding area, which encompassed a large residential community. We hypothesized that previously normal residents in the community surrounding the former WTC would have an increased incidence of persistent respiratory symptoms and abnormalities in screening spirometry. A hybrid cross-sectional and retrospective cohort study using a symptom-based questionnaire and onsite screening spirometry in residents in an exposed area and in a control area was performed 12 +/- 4 months after the collapse. Surveys were analyzed from 2,812 residents. New-onset respiratory symptoms were described by 55.8% of residents in the exposed area, compared with 20.1% in the control area after the event. Persistent new-onset symptoms were identified in 26.4 versus 7.5% of residents in the exposed area versus control area, respectively. No differences in screening spirometry between the groups were detected. A small pilot study suggested the possibility of an increase in bronchial hyperresponsiveness in exposed participants with persistent symptoms. The data demonstrate an increased rate of new-onset and persistent respiratory health effects in residents near the former WTC compared with a control population.	28	71	2005	6		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Viruses in asthma exacerbations. Purpose of review Respiratory viruses are well recognized as major triggers of acute exacerbations of asthma in children and adults, resulting in frequent outpatients visits and hospitalizations, Clinical and epidemiologic evidence supports this association. The application of molecular diagnostic methods has improved understanding of viral epidemiology and the pathophysiological mechanisms involved in viral induced acute asthma. This article reviews publications since October 2002 for an update of the role of viruses in exacerbations of asthma. Recent findings Respiratory viruses are present in most patients hospitalized for life-threatening asthma and acute nonlife-threatening asthma. Rhinovirus is the most common, but coinfection with other viruses may be important. Patients with asthma are not more susceptible to upper respiratory tract rhinovirus infections than healthy people but suffer from more severe consequences of the lower respiratory tract infection. Recent epidemiologic studies suggest that viruses provoke asthma attacks by additive or synergistic interactions with allergen exposure or with air pollution. An impaired antiviral immunity to rhinovirus may lead to impaired viral clearance and hence prolonged symptoms. Respiratory viral infections cause asthmatic exacerbations by triggering recruitment of T(H)2-type cells into the lungs, There is no specific antiviral strategy for prevention of respiratory-triggered asthma exacerbations, although clinical trials of potential antiviral agents are ongoing. Indirect prevention strategies focus on the reduction of overall airway inflammation to reduce the severity of the host response to respiratory viral infections. Summary Respiratory viral infections are a major cause of morbidity and mortality in asthma. There is a lack of specific antiviral strategies in the prevention or reduction of viral-triggered asthma exacerbations. Recent advances in understanding of the epidemiology and immunopathogenesis of respiratory viral infection in asthma provide opportunities or identification of specific targets for antiviral agents and strategies for management and prevention.. exacerbations of asthma| viruses| epidemiology|rhinovirus respiratory-infections| epithelial-cells| influenza vaccination| tract infection| induced sputum| atopic asthma| risk-factors| children| lung| expression.	JAN-2005	exacerbations of asthma| viruses| epidemiology|rhinovirus respiratory-infections| epithelial-cells| influenza vaccination| tract infection| induced sputum| atopic asthma| risk-factors| children| lung| expression	Tan, WC	Viruses in asthma exacerbations		CURRENT OPINION IN PULMONARY MEDICINE	exacerbations of asthma; viruses; epidemiology	RHINOVIRUS RESPIRATORY-INFECTIONS; EPITHELIAL-CELLS; INFLUENZA VACCINATION; TRACT INFECTION; INDUCED SPUTUM; ATOPIC ASTHMA; RISK-FACTORS; CHILDREN; LUNG; EXPRESSION	Purpose of review Respiratory viruses are well recognized as major triggers of acute exacerbations of asthma in children and adults, resulting in frequent outpatients visits and hospitalizations, Clinical and epidemiologic evidence supports this association. The application of molecular diagnostic methods has improved understanding of viral epidemiology and the pathophysiological mechanisms involved in viral induced acute asthma. This article reviews publications since October 2002 for an update of the role of viruses in exacerbations of asthma. Recent findings Respiratory viruses are present in most patients hospitalized for life-threatening asthma and acute nonlife-threatening asthma. Rhinovirus is the most common, but coinfection with other viruses may be important. Patients with asthma are not more susceptible to upper respiratory tract rhinovirus infections than healthy people but suffer from more severe consequences of the lower respiratory tract infection. Recent epidemiologic studies suggest that viruses provoke asthma attacks by additive or synergistic interactions with allergen exposure or with air pollution. An impaired antiviral immunity to rhinovirus may lead to impaired viral clearance and hence prolonged symptoms. Respiratory viral infections cause asthmatic exacerbations by triggering recruitment of T(H)2-type cells into the lungs, There is no specific antiviral strategy for prevention of respiratory-triggered asthma exacerbations, although clinical trials of potential antiviral agents are ongoing. Indirect prevention strategies focus on the reduction of overall airway inflammation to reduce the severity of the host response to respiratory viral infections. Summary Respiratory viral infections are a major cause of morbidity and mortality in asthma. There is a lack of specific antiviral strategies in the prevention or reduction of viral-triggered asthma exacerbations. Recent advances in understanding of the epidemiology and immunopathogenesis of respiratory viral infection in asthma provide opportunities or identification of specific targets for antiviral agents and strategies for management and prevention.	62	71	2005	6		Respiratory System
The master regulators of allergic inflammation: dendritic cells in Th2 sensitization. The development of Th2 responses to inhaled proteins represents a malfunction of the adaptive immune system in that protein antigens are not microbial in nature and should not elicit an adaptive immune reaction. This derailing of the immune system may result from false alarms generated by the innate immune system, resulting in unexpected dendritic cell (DC) maturation after exposure to allergens. Conditions in the local microenvironment during DC maturation may also result in the preferential induction of Th2 responses. Recent progress has been made in our understanding of the role of DCs in both Th2 sensitization to aeroallergens and the regulation of Th2 and Th1 immunity.. t-helper-cell| eosinophilic airway inflammation| toll-like receptors| in-vivo| inhaled antigen| cutting edge| immune-responses| murine model| type-2 th2| differentiation.	DEC-2003	t-helper-cell| eosinophilic airway inflammation| toll-like receptors| in-vivo| inhaled antigen| cutting edge| immune-responses| murine model| type-2 th2| differentiation	Eisenbarth, SC; Piggott, DA; Bottomly, K	The master regulators of allergic inflammation: dendritic cells in Th2 sensitization		CURRENT OPINION IN IMMUNOLOGY		T-HELPER-CELL; EOSINOPHILIC AIRWAY INFLAMMATION; TOLL-LIKE RECEPTORS; IN-VIVO; INHALED ANTIGEN; CUTTING EDGE; IMMUNE-RESPONSES; MURINE MODEL; TYPE-2 TH2; DIFFERENTIATION	The development of Th2 responses to inhaled proteins represents a malfunction of the adaptive immune system in that protein antigens are not microbial in nature and should not elicit an adaptive immune reaction. This derailing of the immune system may result from false alarms generated by the innate immune system, resulting in unexpected dendritic cell (DC) maturation after exposure to allergens. Conditions in the local microenvironment during DC maturation may also result in the preferential induction of Th2 responses. Recent progress has been made in our understanding of the role of DCs in both Th2 sensitization to aeroallergens and the regulation of Th2 and Th1 immunity.	55	71	2003	7	10.1016/j.coi.2003.09.003	Immunology
Pattern of admission to hospitals during muslim pilgrimage (Hajj). Objectives: The pattern of medical conditions necessitating admission differs according to the weather condition in that particular year. Previous studies had been conducted during the hot weather, none over the last 10 years, were carried out during, the milder weather we are experiencing. The aim of this study is to establish the pattern of admission during this mild weather and to elucidate the possible risk factors. Methods: A prospective study was performed in 4 hospitals in 2 different locations in Al-Mashaer, Kingdom of Saudi Arabia. Data were collected during one working shift in 2 hospitals in Arafat on the 9th of Dhul Hijjah 1422, corresponding to 21st of February 2002, and another working shift in 2 hospitals in Mina on the 10th of Dhul Hijjah 1422, corresponding to 22nd of February 2002. Results: A cohort of 76 patients from Arafat hospitals and 84 patients from Mina' hospitals were included (total 160 patients). Males constituted 62% and females 38% with the median age of 60 +/- 15years. The respiratory system was the most commonly affected (57%), followed by cardiovascular system (19.4%), and gastrointestinal tract (GIT) in 6.3% of cases. There were only 3 cases of heat-related admissions with only one confirmed case of heat stroke. Similarly, only one case of meningitis was confirmed in this cohort. Pneumonia was encountered in 63 cases (39.4%) and exacerbation of asthma and chronic obstructive pulmonary diseases (COPD) in 23 cases (14.4%). Pre-existing co-morbid medical conditions had included bronchial asthma and COPD (22.5%), hypertension (17.5%), and Diabetes mellitus (15%). Short-term follow up (24-48 hours) identified 2 deaths (1.3%), 94 patients (59%) were transferred to other secondary or tertiary care facilities and 64 (40%) were discharged home. Conclusion: Hospital admission during Hajj is related to old age and occurs in patients with associated co-morbid conditions. During this mild weather lower respiratory tract infections and exacerbation of bronchial asthma and COPD are the most commonly encountered diseases during Hajj.. saudi-arabia| meningococcal disease| al-munawarah| heatstroke| management| outbreak| makkah.	OCT-2003	saudi-arabia| meningococcal disease| al-munawarah| heatstroke| management| outbreak| makkah	Al-Ghamdi, SM; Akbar, HO; Qari, YA; Fathaldin, OA; Al-Rashed, RS	Pattern of admission to hospitals during muslim pilgrimage (Hajj)		SAUDI MEDICAL JOURNAL		SAUDI-ARABIA; MENINGOCOCCAL DISEASE; AL-MUNAWARAH; HEATSTROKE; MANAGEMENT; OUTBREAK; MAKKAH	Objectives: The pattern of medical conditions necessitating admission differs according to the weather condition in that particular year. Previous studies had been conducted during the hot weather, none over the last 10 years, were carried out during, the milder weather we are experiencing. The aim of this study is to establish the pattern of admission during this mild weather and to elucidate the possible risk factors. Methods: A prospective study was performed in 4 hospitals in 2 different locations in Al-Mashaer, Kingdom of Saudi Arabia. Data were collected during one working shift in 2 hospitals in Arafat on the 9th of Dhul Hijjah 1422, corresponding to 21st of February 2002, and another working shift in 2 hospitals in Mina on the 10th of Dhul Hijjah 1422, corresponding to 22nd of February 2002. Results: A cohort of 76 patients from Arafat hospitals and 84 patients from Mina' hospitals were included (total 160 patients). Males constituted 62% and females 38% with the median age of 60 +/- 15years. The respiratory system was the most commonly affected (57%), followed by cardiovascular system (19.4%), and gastrointestinal tract (GIT) in 6.3% of cases. There were only 3 cases of heat-related admissions with only one confirmed case of heat stroke. Similarly, only one case of meningitis was confirmed in this cohort. Pneumonia was encountered in 63 cases (39.4%) and exacerbation of asthma and chronic obstructive pulmonary diseases (COPD) in 23 cases (14.4%). Pre-existing co-morbid medical conditions had included bronchial asthma and COPD (22.5%), hypertension (17.5%), and Diabetes mellitus (15%). Short-term follow up (24-48 hours) identified 2 deaths (1.3%), 94 patients (59%) were transferred to other secondary or tertiary care facilities and 64 (40%) were discharged home. Conclusion: Hospital admission during Hajj is related to old age and occurs in patients with associated co-morbid conditions. During this mild weather lower respiratory tract infections and exacerbation of bronchial asthma and COPD are the most commonly encountered diseases during Hajj.	15	71	2003	4		General & Internal Medicine
How environmental exposures influence the development and exacerbation of asthma. Environmental exposures may increase a child's risk of developing asthma and also may increase the risk of asthma exacerbations. This article reviews several environmental exposures and suggests whether they contribute to asthma prevalence, asthma exacerbations, or both. Outdoor air exposures and violence are not likely to cause the increase in asthma prevalence. Exposure to outdoor air pollutants primarily leads to increased exacerbations, sometimes manifested as asthma clusters. Clinicians should be alert for space-time clusters of asthma exacerbations in the community, because these clusters may suggest a modifiable point-source exposure. Indoor air exposures are more strongly linked to the increase in asthma prevalence. Exposure to dust mites and tobacco smoke are risk factors for the development of asthma and may also exacerbate existing asthma. Effective measures to prevent exposures to these pollutants are available. With proper management, the amount of environmental exposures can be decreased. Whether decreasing these exposures will result in decreases in asthma prevalence and exacerbations is not yet documented.. asthma| indoor air pollution| outdoor air pollution|house-dust mite| outdoor air-pollution| emergency room visits| childhood asthma| passive smoking| pulmonary-function| epidemic asthma| respiratory health| normal-children| orleans asthma.	JUL-2003	asthma| indoor air pollution| outdoor air pollution|house-dust mite| outdoor air-pollution| emergency room visits| childhood asthma| passive smoking| pulmonary-function| epidemic asthma| respiratory health| normal-children| orleans asthma	Etzel, RA	How environmental exposures influence the development and exacerbation of asthma		PEDIATRICS	asthma; indoor air pollution; outdoor air pollution	HOUSE-DUST MITE; OUTDOOR AIR-POLLUTION; EMERGENCY ROOM VISITS; CHILDHOOD ASTHMA; PASSIVE SMOKING; PULMONARY-FUNCTION; EPIDEMIC ASTHMA; RESPIRATORY HEALTH; NORMAL-CHILDREN; ORLEANS ASTHMA	Environmental exposures may increase a child's risk of developing asthma and also may increase the risk of asthma exacerbations. This article reviews several environmental exposures and suggests whether they contribute to asthma prevalence, asthma exacerbations, or both. Outdoor air exposures and violence are not likely to cause the increase in asthma prevalence. Exposure to outdoor air pollutants primarily leads to increased exacerbations, sometimes manifested as asthma clusters. Clinicians should be alert for space-time clusters of asthma exacerbations in the community, because these clusters may suggest a modifiable point-source exposure. Indoor air exposures are more strongly linked to the increase in asthma prevalence. Exposure to dust mites and tobacco smoke are risk factors for the development of asthma and may also exacerbate existing asthma. Effective measures to prevent exposures to these pollutants are available. With proper management, the amount of environmental exposures can be decreased. Whether decreasing these exposures will result in decreases in asthma prevalence and exacerbations is not yet documented.	121	71	2003	7		Pediatrics
A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis - Evidence for a dose-response relationship. Background: There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases. Methods: This randomized, double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with standardized ragweed pollen extract tablets, in patients with an allergic rhinitis. A total of 110 outpatients were randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a 28-day progression phase, the patients received a maintenance treatment during 6.5 months. Efficacy variables included a global assessment of efficacy (patient/investigator), symptoms and medication scores as well as the frequency of asthma attacks. Results: In the active treatment group, 43 patients completed the study, versus 49 on placebo. During the whole period of pollination, the difference favoring immunotherapy was highly significant for the global assessment by the patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were reported more often in the active treatment but mild or moderate, and they abated after dose adjustment. A subgroup analysis of those patients receiving the highest dose of immunotherapy (3 tablets 3 times a week) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages. Conclusion: This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship. Copyright (C) 2003 S. Karger AG, Basel. sublingual-swallow immunotherapy| ragweed| seasonal rhinitis|house-dust mite| allergic rhinoconjunctivitis| swallow immunotherapy| clinical efficacy| controlled trial| pollen extract| children| asthma| sensitizations.	JUN-2003	sublingual-swallow immunotherapy| ragweed| seasonal rhinitis|house-dust mite| allergic rhinoconjunctivitis| swallow immunotherapy| clinical efficacy| controlled trial| pollen extract| children| asthma| sensitizations	Andre, C; Perrin-Fayolle, M; Grosclaude, M; Couturier, P; Basset, D; Cornillon, J; Piperno, D; Girodet, B; Sanchez, R; Vallon, C; Bellier, P; Nasr, M	A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis - Evidence for a dose-response relationship		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	sublingual-swallow immunotherapy; ragweed; seasonal rhinitis	HOUSE-DUST MITE; ALLERGIC RHINOCONJUNCTIVITIS; SWALLOW IMMUNOTHERAPY; CLINICAL EFFICACY; CONTROLLED TRIAL; POLLEN EXTRACT; CHILDREN; ASTHMA; SENSITIZATIONS	Background: There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases. Methods: This randomized, double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with standardized ragweed pollen extract tablets, in patients with an allergic rhinitis. A total of 110 outpatients were randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a 28-day progression phase, the patients received a maintenance treatment during 6.5 months. Efficacy variables included a global assessment of efficacy (patient/investigator), symptoms and medication scores as well as the frequency of asthma attacks. Results: In the active treatment group, 43 patients completed the study, versus 49 on placebo. During the whole period of pollination, the difference favoring immunotherapy was highly significant for the global assessment by the patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were reported more often in the active treatment but mild or moderate, and they abated after dose adjustment. A subgroup analysis of those patients receiving the highest dose of immunotherapy (3 tablets 3 times a week) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages. Conclusion: This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship. Copyright (C) 2003 S. Karger AG, Basel	19	71	2003	8	10.1159/000070926	Allergy; Immunology
Effects of respiratory Mycoplasma pneumoniae infection on allerizen-induced bronchial hyperresponsiveness and lung inflammation in mice. Airway mycoplasma infection may be associated with asthma pathophysiology. However, the direct effects of mycoplasma infection on asthma remain unknown. Using a murine allergic-asthma model, we evaluated the effects of different timing of airway Mycoplasma pneumoniae infection on bronchial hyperresponsiveness (BHR), lung inflammation, and the protein levels of Th1 (gamma interferon [IFN-gamma]) and Th2 (interleukin 4 [IL-4]) cytokines in bronchoalveolar lavage fluid. When mycoplasma infection occurred 3 days before allergen (ovalbumin) sensitization and challenge, the infection reduced the BHR and inflammatory-cell influx into the lung. This was accompanied by a significant induction of Th1 responses (increased IFN-gamma and decreased IL-4 production). Conversely, when mycoplasma infection occurred 2 days after allergen sensitization and challenge, the infection initially caused a temporary reduction of BHR and then increased BHR, lung inflammation, and IL-4 levels. Our data suggest that mycoplasma infection could modulate both physiological and immunological responses in the murine asthma model. Our animal models may also provide a new means to understand the role of infection in asthma pathogenesis and give evidence for the asthma hygiene hypothesis.. house-dust endotoxin| chlamydia-pneumoniae| immune-response| chronic asthma| murine model| disease| adults| sensitization| children| exposure.	MAR-2003	house-dust endotoxin| chlamydia-pneumoniae| immune-response| chronic asthma| murine model| disease| adults| sensitization| children| exposure	Chu, HW; Honour, JM; Rawlinson, CA; Harbeck, RJ; Martin, RJ	Effects of respiratory Mycoplasma pneumoniae infection on allerizen-induced bronchial hyperresponsiveness and lung inflammation in mice		INFECTION AND IMMUNITY		HOUSE-DUST ENDOTOXIN; CHLAMYDIA-PNEUMONIAE; IMMUNE-RESPONSE; CHRONIC ASTHMA; MURINE MODEL; DISEASE; ADULTS; SENSITIZATION; CHILDREN; EXPOSURE	Airway mycoplasma infection may be associated with asthma pathophysiology. However, the direct effects of mycoplasma infection on asthma remain unknown. Using a murine allergic-asthma model, we evaluated the effects of different timing of airway Mycoplasma pneumoniae infection on bronchial hyperresponsiveness (BHR), lung inflammation, and the protein levels of Th1 (gamma interferon [IFN-gamma]) and Th2 (interleukin 4 [IL-4]) cytokines in bronchoalveolar lavage fluid. When mycoplasma infection occurred 3 days before allergen (ovalbumin) sensitization and challenge, the infection reduced the BHR and inflammatory-cell influx into the lung. This was accompanied by a significant induction of Th1 responses (increased IFN-gamma and decreased IL-4 production). Conversely, when mycoplasma infection occurred 2 days after allergen sensitization and challenge, the infection initially caused a temporary reduction of BHR and then increased BHR, lung inflammation, and IL-4 levels. Our data suggest that mycoplasma infection could modulate both physiological and immunological responses in the murine asthma model. Our animal models may also provide a new means to understand the role of infection in asthma pathogenesis and give evidence for the asthma hygiene hypothesis.	26	71	2003	7	10.1128/IAI.71.3.1520-1526.2003	Immunology; Infectious Diseases
Receptor-mediated effects of nicotine and its nitrosated derivative NNK on pulmonary neuroendocrine cells. Pulmonary neuroendocrine cells (PNECs) have been implicated in the development of small cell lung carcinoma (SCLC) and pediatric asthma, and smoking is a risk factor for both diseases. We as well as others have shown that the alpha(7) nicotinic acetylcholine receptor (alpha(7) nAChR) regulates the release of 5-hydroxytryptamine (5-HT, serotonin) in PNECs and SCLC. Serotonin is an autocrine growth factor for PNECs and SCLC and acts as bronchoconstrictor. We found that nicotine and its nitrosated carcinogenic derivative 4.(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) bind to the alpha(7) nAChR in SCLC and PNECs, resulting in the influx of Ca2+, release of 5-HT, and activation of a mitogenic pathway mediated by protein kinase C (PKC), Raf-1, mitogen activated protein kinase (MAPK) and c-myc. Exposure to 10% CO2 acted synergistically. Unstimulated SCLC cells from smokers demonstrated high base levels of 5-HT release and of individual downstream signaling components in comparison to PNECs. Subchronic exposure of PNECs to NNK up-regulated the alpha(7) nAChR and its associated serotonergic mitogenic pathway in PNECs, an effect that may contribute to the development of SCLC in smokers and pediatric asthma in children of mothers who smoke. (C) 2003 Wiley-Liss, Inc.. pnec| sclc| alpha(7)nachr| asthma| nicotine| nnk|tobacco-specific carcinogen| lung-cancer| n-nitrosamines| neuroepithelial bodies| acetylcholine-receptor| airway chemoreceptors| dna methylation| point mutations| carbon-dioxide| never-smokers.	JAN-2003	pnec| sclc| alpha(7)nachr| asthma| nicotine| nnk|tobacco-specific carcinogen| lung-cancer| n-nitrosamines| neuroepithelial bodies| acetylcholine-receptor| airway chemoreceptors| dna methylation| point mutations| carbon-dioxide| never-smokers	Schuller, HM; Plummer, HK; Jull, BA	Receptor-mediated effects of nicotine and its nitrosated derivative NNK on pulmonary neuroendocrine cells		ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY	PNEC; SCLC; alpha(7)nAChR; asthma; nicotine; NNK	TOBACCO-SPECIFIC CARCINOGEN; LUNG-CANCER; N-NITROSAMINES; NEUROEPITHELIAL BODIES; ACETYLCHOLINE-RECEPTOR; AIRWAY CHEMORECEPTORS; DNA METHYLATION; POINT MUTATIONS; CARBON-DIOXIDE; NEVER-SMOKERS	Pulmonary neuroendocrine cells (PNECs) have been implicated in the development of small cell lung carcinoma (SCLC) and pediatric asthma, and smoking is a risk factor for both diseases. We as well as others have shown that the alpha(7) nicotinic acetylcholine receptor (alpha(7) nAChR) regulates the release of 5-hydroxytryptamine (5-HT, serotonin) in PNECs and SCLC. Serotonin is an autocrine growth factor for PNECs and SCLC and acts as bronchoconstrictor. We found that nicotine and its nitrosated carcinogenic derivative 4.(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) bind to the alpha(7) nAChR in SCLC and PNECs, resulting in the influx of Ca2+, release of 5-HT, and activation of a mitogenic pathway mediated by protein kinase C (PKC), Raf-1, mitogen activated protein kinase (MAPK) and c-myc. Exposure to 10% CO2 acted synergistically. Unstimulated SCLC cells from smokers demonstrated high base levels of 5-HT release and of individual downstream signaling components in comparison to PNECs. Subchronic exposure of PNECs to NNK up-regulated the alpha(7) nAChR and its associated serotonergic mitogenic pathway in PNECs, an effect that may contribute to the development of SCLC in smokers and pediatric asthma in children of mothers who smoke. (C) 2003 Wiley-Liss, Inc.	56	71	2003	8	10.1002/ar.a.10019	Anatomy & Morphology
Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis. Prostaglandin D-2 is known to be the major prostanoid produced by allergen-activated mast cells, but its role in the formation of allergic diseases is not well established because of complexity of its receptor system and lack of appropriate inhibitors. We have recently identified a new-type prostaglandin D2 receptor, named CRTH2. Studies with normal subjects have shown that CRTH2 appears to be selectively expressed by T helper 2 cells but not T helper 1 cells among circulating CD4(+) lymphocytes. The exact correlation between CRTH2 and T helper 2 cells in various disease settings and the impact of CRTH2-mediated prostaglandin D-2 activities on various T helper 2 responses in vivo still remain to be elucidated, however. In this study, we investigated the correlation between CRTH2 and T helper 2 cells among circulating CD4+ lymphocytes in normal adults and patients with atopic dermatitis, a T-helper-2-involving disease. The results showed that virtually all CRTH2(+)CD4(+) lymphocytes had a pure T helper 2 phenotype and formed not all but a large proportion of circulating T helper 2 cells for both normal and atopic dermatitis subjects. In chemotaxis assays, peripheral blood CRTH2(+)CD4(+) lymphocytes were significantly attracted by prostaglandin D2 as well as by a typical T-helper-2-attracting chemokine, thymus and activation regulated chemokine, whereas they showed little chemotactic migration toward typical T-helper-1-attracting chemokines, macrophage inflammatory protein 1beta and interferon-gamma inducible protein 10. Furthermore, in atopic dermatitis patients, a preferential increase of CRTH2(+) cells was noted within the disease-related cutaneous lymphocyte-associated antigen-positive, but not the cutaneous lymphocyte-associated antigen-negative, CD4(+) lymphocyte compartment. Our results suggest the involvement of the prostaglandin D-2/CRTH2 system in both normal and pathogenic T helper 2 responses.. cell surface receptors| chemotaxis| flow cytometry| human| t lymphocyte subsets|lymphocyte-associated antigen| chemokine receptors| th2 cells| in-situ| selective expression| cytokine pattern| t-helper-2 cells| surface-molecule| homing receptor| human cd4(+).	SEP-2002	cell surface receptors| chemotaxis| flow cytometry| human| t lymphocyte subsets|lymphocyte-associated antigen| chemokine receptors| th2 cells| in-situ| selective expression| cytokine pattern| t-helper-2 cells| surface-molecule| homing receptor| human cd4(+)	Iwasaki, M; Nagata, K; Takano, S; Takahashi, K; Ishii, N; Ikezawa, Z	Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2 cells in patients with atopic dermatitis		JOURNAL OF INVESTIGATIVE DERMATOLOGY	cell surface receptors; chemotaxis; flow cytometry; human; T lymphocyte subsets	LYMPHOCYTE-ASSOCIATED ANTIGEN; CHEMOKINE RECEPTORS; TH2 CELLS; IN-SITU; SELECTIVE EXPRESSION; CYTOKINE PATTERN; T-HELPER-2 CELLS; SURFACE-MOLECULE; HOMING RECEPTOR; HUMAN CD4(+)	Prostaglandin D-2 is known to be the major prostanoid produced by allergen-activated mast cells, but its role in the formation of allergic diseases is not well established because of complexity of its receptor system and lack of appropriate inhibitors. We have recently identified a new-type prostaglandin D2 receptor, named CRTH2. Studies with normal subjects have shown that CRTH2 appears to be selectively expressed by T helper 2 cells but not T helper 1 cells among circulating CD4(+) lymphocytes. The exact correlation between CRTH2 and T helper 2 cells in various disease settings and the impact of CRTH2-mediated prostaglandin D-2 activities on various T helper 2 responses in vivo still remain to be elucidated, however. In this study, we investigated the correlation between CRTH2 and T helper 2 cells among circulating CD4+ lymphocytes in normal adults and patients with atopic dermatitis, a T-helper-2-involving disease. The results showed that virtually all CRTH2(+)CD4(+) lymphocytes had a pure T helper 2 phenotype and formed not all but a large proportion of circulating T helper 2 cells for both normal and atopic dermatitis subjects. In chemotaxis assays, peripheral blood CRTH2(+)CD4(+) lymphocytes were significantly attracted by prostaglandin D2 as well as by a typical T-helper-2-attracting chemokine, thymus and activation regulated chemokine, whereas they showed little chemotactic migration toward typical T-helper-1-attracting chemokines, macrophage inflammatory protein 1beta and interferon-gamma inducible protein 10. Furthermore, in atopic dermatitis patients, a preferential increase of CRTH2(+) cells was noted within the disease-related cutaneous lymphocyte-associated antigen-positive, but not the cutaneous lymphocyte-associated antigen-negative, CD4(+) lymphocyte compartment. Our results suggest the involvement of the prostaglandin D-2/CRTH2 system in both normal and pathogenic T helper 2 responses.	56	71	2002	8	10.1046/j.1523-1747.2002.01862.x	Dermatology
A novel mouse model of diisocyanate-induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge. Background: Exposure to diisocyanates, a group of highly reactive, low-molecular-weight compounds, is a major cause of occupational asthma. In contrast to mouse models of atopic asthma, previous mouse models of diisocyanate-induced asthma have failed to show lung inflammation with characteristics of human disease. Objective: Our goal was to establish a novel mouse model of diisocyanate-induced asthma in which lung inflammation reminiscent of that seen in human asthma is generated after inhaled antigen challenge. Methods: BALB/c mice were epicutaneously sensitized to hexamethylene diisocyanate (HDI) and then challenged with an HDI-protein conjugate administered by means of an intranasal droplet. Results: HDI sensitization resulted in development of contact hypersensitivity and HDI-specific antibody production. Most importantly, however, vigorous inflammatory responses with characteristics of human asthma were generated in the lung after inhaled HDI challenge. Challenge of sensitized, but not unsensitized, mice resulted in airway eosinophilia, mucus hypersecretion, and production of T(H)1-type (IFN-gamma) and T(H)2 type (IL-4, IL-5, and IL-13) cytokines by lung inflammatory cells. Despite the mixed T(H)1/T(H)2 response induced by HDI sensitization, use of cytokine-dericient mice revealed that airway eosinophilia was mediated by T(H)2 cytokines and not by IFN-gamma. Conclusion: We report a novel mouse model of diisocyanate-induced asthma that, in contrast to previous models, demonstrates antigen-induced lung inflammation with characteristics of human disease. This model will allow investigation of the immunopathogenesis of diisocyanate-induced asthma and should provide insight into this common form of occupational disease.. asthma| diisocyanate| skin| airway| lung| eosinophils| t(h)2| il-4| il-13| ifn-gamma|human serum-albumin| toluene diisocyanate| occupational asthma| nonatopic asthma| bronchial-mucosa| interferon-gamma| exposure| workers| il-4| isocyanates.	MAY-2002	asthma| diisocyanate| skin| airway| lung| eosinophils| t(h)2| il-4| il-13| ifn-gamma|human serum-albumin| toluene diisocyanate| occupational asthma| nonatopic asthma| bronchial-mucosa| interferon-gamma| exposure| workers| il-4| isocyanates	Herrick, CA; Xu, L; Wisnewski, AV; Das, J; Redlich, CA; Bottomly, K	A novel mouse model of diisocyanate-induced asthma showing allergic-type inflammation in the lung after inhaled antigen challenge		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; diisocyanate; skin; airway; lung; eosinophils; T(H)2; IL-4; IL-13; IFN-gamma	HUMAN SERUM-ALBUMIN; TOLUENE DIISOCYANATE; OCCUPATIONAL ASTHMA; NONATOPIC ASTHMA; BRONCHIAL-MUCOSA; INTERFERON-GAMMA; EXPOSURE; WORKERS; IL-4; ISOCYANATES	Background: Exposure to diisocyanates, a group of highly reactive, low-molecular-weight compounds, is a major cause of occupational asthma. In contrast to mouse models of atopic asthma, previous mouse models of diisocyanate-induced asthma have failed to show lung inflammation with characteristics of human disease. Objective: Our goal was to establish a novel mouse model of diisocyanate-induced asthma in which lung inflammation reminiscent of that seen in human asthma is generated after inhaled antigen challenge. Methods: BALB/c mice were epicutaneously sensitized to hexamethylene diisocyanate (HDI) and then challenged with an HDI-protein conjugate administered by means of an intranasal droplet. Results: HDI sensitization resulted in development of contact hypersensitivity and HDI-specific antibody production. Most importantly, however, vigorous inflammatory responses with characteristics of human asthma were generated in the lung after inhaled HDI challenge. Challenge of sensitized, but not unsensitized, mice resulted in airway eosinophilia, mucus hypersecretion, and production of T(H)1-type (IFN-gamma) and T(H)2 type (IL-4, IL-5, and IL-13) cytokines by lung inflammatory cells. Despite the mixed T(H)1/T(H)2 response induced by HDI sensitization, use of cytokine-dericient mice revealed that airway eosinophilia was mediated by T(H)2 cytokines and not by IFN-gamma. Conclusion: We report a novel mouse model of diisocyanate-induced asthma that, in contrast to previous models, demonstrates antigen-induced lung inflammation with characteristics of human disease. This model will allow investigation of the immunopathogenesis of diisocyanate-induced asthma and should provide insight into this common form of occupational disease.	31	71	2002	6	10.1067/mai.2002.123533	Allergy; Immunology
Role of sulfite additives in wine induced asthma: Single dose and cumulative dose studies. Background-Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose sulfited wine challenge protocol was employe to establish if wine sensitive asthmatics as a group have an increased sensitivity to sulfites. Methods-In study 1, 24 asthmatic patients with a strong history of wine induced asthma were screened. Subjects showing positive responses to single blind high sulfite (300 ppm) wine challenge were rechallenged on separate days in a double blind, placebo controlled fashion with wines of varying sulfite levels to characterise their responses to these drinks. In study 2, wine sensitive asthmatic patients (n=12) and control asthmatics (n=6) were challenged cumulatively with wine containing increasing concentrations of sulfite in order to characterise further their sensitivity to sulfites in wine. Results-Four of the 24 self-reporting wine sensitive asthmatic patients were found to respond to sulfite additives in wine when challenged in a single dose fashion (study 1). In the double blind dose-response study all four had a significant fall in forced expiratory volume in one second (FEV) (> 15% from baseline) following exposure to wine containing 300 ppm sulfite, but did not respond to wines containing 20, 75 or 150 ppm sulfite. Responses were maximal at 5 minutes (mean (SD) maximal decline in FEV, 28.7 (13)%) and took 15-60 minutes to return to baseline levels. In the cumulative dose-response study (study 2) no significant difference was observed in any of the lung function parameters measured (FEV,, peak expiratory flow (PEF), mid phase forced expiratory flow (FEF25-75)) between wine sensitive and normal asthmatic subjects. Conclusions-Only a small number of wine sensitive asthmatic patients responded to a single dose challenge with sulfited wine under laboratory conditions. This may suggest that the role of sulfites and/or wine in triggering asthmatic responses has been overestimated. Alternatively, cofactors or other components in wine may play an important role in wine induced asthma. Cumulative sulfite dose challenges did not detect an increased sensitivity to sulfite in wine sensitive asthmatics and an alternative approach to identifying sulfite/wine sensitive asthma may be required.. asthma| wine| sulfite additives|metabisulfite-induced bronchoconstriction| sodium metabisulfite| challenge| responses.	OCT-2001	asthma| wine| sulfite additives|metabisulfite-induced bronchoconstriction| sodium metabisulfite| challenge| responses	Vally, H; Thompson, PJ	Role of sulfite additives in wine induced asthma: Single dose and cumulative dose studies		THORAX	asthma; wine; sulfite additives	METABISULFITE-INDUCED BRONCHOCONSTRICTION; SODIUM METABISULFITE; CHALLENGE; RESPONSES	Background-Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose sulfited wine challenge protocol was employe to establish if wine sensitive asthmatics as a group have an increased sensitivity to sulfites. Methods-In study 1, 24 asthmatic patients with a strong history of wine induced asthma were screened. Subjects showing positive responses to single blind high sulfite (300 ppm) wine challenge were rechallenged on separate days in a double blind, placebo controlled fashion with wines of varying sulfite levels to characterise their responses to these drinks. In study 2, wine sensitive asthmatic patients (n=12) and control asthmatics (n=6) were challenged cumulatively with wine containing increasing concentrations of sulfite in order to characterise further their sensitivity to sulfites in wine. Results-Four of the 24 self-reporting wine sensitive asthmatic patients were found to respond to sulfite additives in wine when challenged in a single dose fashion (study 1). In the double blind dose-response study all four had a significant fall in forced expiratory volume in one second (FEV) (> 15% from baseline) following exposure to wine containing 300 ppm sulfite, but did not respond to wines containing 20, 75 or 150 ppm sulfite. Responses were maximal at 5 minutes (mean (SD) maximal decline in FEV, 28.7 (13)%) and took 15-60 minutes to return to baseline levels. In the cumulative dose-response study (study 2) no significant difference was observed in any of the lung function parameters measured (FEV,, peak expiratory flow (PEF), mid phase forced expiratory flow (FEF25-75)) between wine sensitive and normal asthmatic subjects. Conclusions-Only a small number of wine sensitive asthmatic patients responded to a single dose challenge with sulfited wine under laboratory conditions. This may suggest that the role of sulfites and/or wine in triggering asthmatic responses has been overestimated. Alternatively, cofactors or other components in wine may play an important role in wine induced asthma. Cumulative sulfite dose challenges did not detect an increased sensitivity to sulfite in wine sensitive asthmatics and an alternative approach to identifying sulfite/wine sensitive asthma may be required.	22	71	2001	7	10.1136/thorax.56.10.763	Respiratory System
In utero and perinatal complications preceding asthma. Background: It has been suggested that pregnancy and early life may influence the development of asthma in the offspring, but published studies have not carefully controlled for potential biases. Methods: In a large British birth cohort of 4065 natural children of 2583 mothers, we investigated whether in utero and perinatal influences contribute to the development and the severity of asthma in childhood, allowing for possible confounders of the relationship, and considering the nonindependence of familial data. Results: Child asthma (10.1%) was more frequently reported by mothers when there had been health complications during pregnancy (prevalence = 14.3%; adjusted odds ratio [ORadj] = 2.01; 95% confidence interval, 1.52-2.67), labor, or delivery (19.3%, ORadj = 1.35, 1.01-1.81); child illness or health complications during the first week of life (22.6%, ORadj = 1.35, 1.01-1.82); and birth weight of < 2.5 kg (7.0%, ORadj = 1.57, 1.10-2.25). Specific causes of health complications during pregnancy which significantly related to asthma were early or threatened labor (ICD: 644) (4.8%, ORadj = 1.58, 1.03-2.40) and the malposition or malpresentation of the fetus (ICD: 652) (1.6%, ORadj = 3.63, 1.47-8.91). Conclusions: The results provide further evidence that in utero and perinatal factors may increase the risk of developing asthma.. asthma| birth weight| family history| in utero| in utero exposure to smoking| labor| malpresentation of fetus| passive smoking| perinatal| pregnancy| risk factors| threatened labor|childhood asthma| risk factor| respiratory-disease| bronchial-asthma| pregnancy| birth| epidemiology| prematurity| morbidity| exposure.	JUN-2001	asthma| birth weight| family history| in utero| in utero exposure to smoking| labor| malpresentation of fetus| passive smoking| perinatal| pregnancy| risk factors| threatened labor|childhood asthma| risk factor| respiratory-disease| bronchial-asthma| pregnancy| birth| epidemiology| prematurity| morbidity| exposure	Annesi-Maesano, I; Moreau, D; Strachan, D	In utero and perinatal complications preceding asthma		ALLERGY	asthma; birth weight; family history; in utero; in utero exposure to smoking; labor; malpresentation of fetus; passive smoking; perinatal; pregnancy; risk factors; threatened labor	CHILDHOOD ASTHMA; RISK FACTOR; RESPIRATORY-DISEASE; BRONCHIAL-ASTHMA; PREGNANCY; BIRTH; EPIDEMIOLOGY; PREMATURITY; MORBIDITY; EXPOSURE	Background: It has been suggested that pregnancy and early life may influence the development of asthma in the offspring, but published studies have not carefully controlled for potential biases. Methods: In a large British birth cohort of 4065 natural children of 2583 mothers, we investigated whether in utero and perinatal influences contribute to the development and the severity of asthma in childhood, allowing for possible confounders of the relationship, and considering the nonindependence of familial data. Results: Child asthma (10.1%) was more frequently reported by mothers when there had been health complications during pregnancy (prevalence = 14.3%; adjusted odds ratio [ORadj] = 2.01; 95% confidence interval, 1.52-2.67), labor, or delivery (19.3%, ORadj = 1.35, 1.01-1.81); child illness or health complications during the first week of life (22.6%, ORadj = 1.35, 1.01-1.82); and birth weight of < 2.5 kg (7.0%, ORadj = 1.57, 1.10-2.25). Specific causes of health complications during pregnancy which significantly related to asthma were early or threatened labor (ICD: 644) (4.8%, ORadj = 1.58, 1.03-2.40) and the malposition or malpresentation of the fetus (ICD: 652) (1.6%, ORadj = 3.63, 1.47-8.91). Conclusions: The results provide further evidence that in utero and perinatal factors may increase the risk of developing asthma.	33	71	2001	7	10.1034/j.1398-9995.2001.056006491.x	Allergy; Immunology
Grass pollen immunotherapy: Symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa during the pollen season. Background: Tissue eosinophilia and infiltration by T(H)2-type T tells are characteristic features of allergic rhinitis both after allergen challenge and during natural allergen exposure. Specific immunotherapy inhibits allergen-induced nasal eosinophilia. Objectives: We sought to assess, in the context of a randomized trial, the relationships between symptomatic improvement after immunotherapy and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season. Methods: Nasal biopsy specimens were taken from 37 adults with severe summer hay fever at baseline (out of season) and at peak season after 2 years of treatment with a depot grass pollen extract or placebo. Biopsy specimens were processed for immunohistochemistry by using mAbs against eosinophils (EG2), T cells (CD3), and IL-2 receptor-positive cells (CD25), as well as for in situ hybridization by using a sulfur 35-labeled antisense riboprobe directed against IL-5. Results: Immunotherapy significantly reduced symptoms (49%, P = .01) and medication requirements (80%, P = .007) compared with placebo. There was a 400% increase (P = .004) in eosinophils during the pollen season in placebo-treated patients, which was inhibited in the immunotherapy group (20% increase, P = .04 between groups). Seasonal increases were also observed for CD25(+) cells (P = .002), CD3(+) cells (P = .02), and IL-5 mRNA-expressing cells (P = .03) in the placebo group but not in the immunotherapy group. A significant correlation was observed between eosinophils and IL-5 expression (r = 0.5, P < .05). Both eosinophils (r = 0.6, P < .02) and IL-5 (r = 0.6, P < .02) correlated with symptoms after immunotherapy. Conclusion: Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season. Conclusion: Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season.. allergic rhinitis| eosinophils| il-5| immunotherapy|recombinant human interleukin-5| natural allergen exposure| colony-stimulating factor| messenger-rna expression| mast-cells| tissue eosinophilia| induced rhinitis| hay-fever| asthma| inflammation.	JUN-2001	allergic rhinitis| eosinophils| il-5| immunotherapy|recombinant human interleukin-5| natural allergen exposure| colony-stimulating factor| messenger-rna expression| mast-cells| tissue eosinophilia| induced rhinitis| hay-fever| asthma| inflammation	Wilson, DR; Nouri-Aria, KT; Walker, SM; Pajno, GB; O'Brien, F; Jacobson, MR; Mackay, IS; Durham, SR	Grass pollen immunotherapy: Symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa during the pollen season		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergic rhinitis; eosinophils; IL-5; immunotherapy	RECOMBINANT HUMAN INTERLEUKIN-5; NATURAL ALLERGEN EXPOSURE; COLONY-STIMULATING FACTOR; MESSENGER-RNA EXPRESSION; MAST-CELLS; TISSUE EOSINOPHILIA; INDUCED RHINITIS; HAY-FEVER; ASTHMA; INFLAMMATION	Background: Tissue eosinophilia and infiltration by T(H)2-type T tells are characteristic features of allergic rhinitis both after allergen challenge and during natural allergen exposure. Specific immunotherapy inhibits allergen-induced nasal eosinophilia. Objectives: We sought to assess, in the context of a randomized trial, the relationships between symptomatic improvement after immunotherapy and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season. Methods: Nasal biopsy specimens were taken from 37 adults with severe summer hay fever at baseline (out of season) and at peak season after 2 years of treatment with a depot grass pollen extract or placebo. Biopsy specimens were processed for immunohistochemistry by using mAbs against eosinophils (EG2), T cells (CD3), and IL-2 receptor-positive cells (CD25), as well as for in situ hybridization by using a sulfur 35-labeled antisense riboprobe directed against IL-5. Results: Immunotherapy significantly reduced symptoms (49%, P = .01) and medication requirements (80%, P = .007) compared with placebo. There was a 400% increase (P = .004) in eosinophils during the pollen season in placebo-treated patients, which was inhibited in the immunotherapy group (20% increase, P = .04 between groups). Seasonal increases were also observed for CD25(+) cells (P = .002), CD3(+) cells (P = .02), and IL-5 mRNA-expressing cells (P = .03) in the placebo group but not in the immunotherapy group. A significant correlation was observed between eosinophils and IL-5 expression (r = 0.5, P < .05). Both eosinophils (r = 0.6, P < .02) and IL-5 (r = 0.6, P < .02) correlated with symptoms after immunotherapy. Conclusion: Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season. Conclusion: Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season.	41	71	2001	6	10.1067/mai.2001.115483	Allergy; Immunology
Reducing relative humidity is a practical way to control dust mites and their allergens in homes in temperate climates. Background: Maintaining a relative humidity [RH) of less than 50% is one recommendation fur reducing numbers of house dust mites and their allergens in homes, Objective: The purpose of this study was to determine whether, in a humid temperate climate, indoor RH could be sufficiently lowered to control dust mites and their allergens. Methods: During a period spanning 2 humid summers (May 1998 to October 1999), dust mite and allergen densities were determined in 3 groups of homes. One group (low RH group, n = 23) maintained an RN of less than 51%, Most of these homes used a high-efficiency dehumidifier and air conditioning. A second group of homes (group A) used air conditioning only (n = 19) or air conditioning and dehumidification (n = 5) but did not maintain an RH of less than 51%, A third group of homes (group C, n = 24) controlled climate by opening windows and had an RH of greater than 51%. Normal housecleaning was maintained in all homes during the study, Results: The low RH group homes started in June with a mean +/- SE of 401 +/- 124 live mites and 17 +/- 3 mug of total Der 1 allergen per gram of dust. After 17 months of maintaining an RH of less than 51%, these declined significantly to 8 +/- 3 live mites per gram LP =.004) and 4 +/- 1 mug of Der 1 per gram of dust (P <.001). In contrast, group A and C homes exhibited seasonal peaks of 500 to 1000 mites and 40 to 70 <mu>g of Der 1 per gram of dust At all time points after the baseline sample, the low RH group homes had significantly less (P <.001) allergen than the group A and C homes, After 17 months, allergen levels were more than 10 Limes lo,Per in low Rfi homes compared with humid homes, Conclusion: This study showed that it is practical to maintain an indoor RH of less than 51% during the humid summer season in a temperate climate, and this resulted in significant reductions in mite and allergen levels.. house dust mites| relative humidity| dehumidification| allergen| der p 1| der f 1| dermatophagoides species|dermatophagoides-farinae acari| mechanical ventilation| water-balance| house| pyroglyphidae| air| pteronyssinus| reduction| prevalence| efficacy.	JAN-2001	house dust mites| relative humidity| dehumidification| allergen| der p 1| der f 1| dermatophagoides species|dermatophagoides-farinae acari| mechanical ventilation| water-balance| house| pyroglyphidae| air| pteronyssinus| reduction| prevalence| efficacy	Arlian, LG; Neal, JS; Morgan, MS; Vyszenski-Moher, DL; Rapp, CM; Alexander, AK	Reducing relative humidity is a practical way to control dust mites and their allergens in homes in temperate climates		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	house dust mites; relative humidity; dehumidification; allergen; Der p 1; Der f 1; dermatophagoides species	DERMATOPHAGOIDES-FARINAE ACARI; MECHANICAL VENTILATION; WATER-BALANCE; HOUSE; PYROGLYPHIDAE; AIR; PTERONYSSINUS; REDUCTION; PREVALENCE; EFFICACY	Background: Maintaining a relative humidity [RH) of less than 50% is one recommendation fur reducing numbers of house dust mites and their allergens in homes, Objective: The purpose of this study was to determine whether, in a humid temperate climate, indoor RH could be sufficiently lowered to control dust mites and their allergens. Methods: During a period spanning 2 humid summers (May 1998 to October 1999), dust mite and allergen densities were determined in 3 groups of homes. One group (low RH group, n = 23) maintained an RN of less than 51%, Most of these homes used a high-efficiency dehumidifier and air conditioning. A second group of homes (group A) used air conditioning only (n = 19) or air conditioning and dehumidification (n = 5) but did not maintain an RH of less than 51%, A third group of homes (group C, n = 24) controlled climate by opening windows and had an RH of greater than 51%. Normal housecleaning was maintained in all homes during the study, Results: The low RH group homes started in June with a mean +/- SE of 401 +/- 124 live mites and 17 +/- 3 mug of total Der 1 allergen per gram of dust. After 17 months of maintaining an RH of less than 51%, these declined significantly to 8 +/- 3 live mites per gram LP =.004) and 4 +/- 1 mug of Der 1 per gram of dust (P <.001). In contrast, group A and C homes exhibited seasonal peaks of 500 to 1000 mites and 40 to 70 <mu>g of Der 1 per gram of dust At all time points after the baseline sample, the low RH group homes had significantly less (P <.001) allergen than the group A and C homes, After 17 months, allergen levels were more than 10 Limes lo,Per in low Rfi homes compared with humid homes, Conclusion: This study showed that it is practical to maintain an indoor RH of less than 51% during the humid summer season in a temperate climate, and this resulted in significant reductions in mite and allergen levels.	32	71	2001	6	10.1067/mai.2001.112119	Allergy; Immunology
In vivo nasal challenge with diesel exhaust particles enhances expression of the CC chemokines rantes, MIP-1 alpha, and MCP-3 in humans. Diesel exhaust particles (DEP) enhance allergic inflammation by increasing in vivo IgE and cytokine production in the human upper respiratory mucosa. CC chemokines have been shown to play an important role in inflammation. We examined whether DEP could alter the production of CC chemokines by cells residing in the human nasal mucosa. At both 6 and 24 h following intranasal DEP challenge, the levels of nasal RANTES, MIP-1 alpha, and MCP-3 were significantly elevated compared to baseline. In contrast, DEP did not enhance levels of Eotaxin at any time, demonstrating that the action of DEP was not simply a global effect on all CC chemokines. Challenge with saline resulted in no significant change in expression of any chemokine at any time. Challenge with DEP also resulted in an increase in total cell counts in nasal lavage fluids. Increases in lymphocyte, monocyte/macrophage, and neutrophil cells were observed but there was no change in eosinophil cell numbers. In contrast, there was a significant enhancement of ECP protein levels in washes performed 6 to 24 h after DEP challenge. Elevated specific nasal chemokine expression following exposure to DEP likely participates in the inflammation, cellular infiltration, and increase in IgE observed in the absence of allergen. (C) 2000 Academic Press.. diesel| pollution| chemokines| allergy| inflammation|in-vivo| messenger-rna| allergic inflammation| cytokine production| mononuclear-cells| ragweed allergen| ige production| responses| eotaxin| eosinophils.	NOV-2000	diesel| pollution| chemokines| allergy| inflammation|in-vivo| messenger-rna| allergic inflammation| cytokine production| mononuclear-cells| ragweed allergen| ige production| responses| eotaxin| eosinophils	Diaz-Sanchez, D; Jyrala, M; Ng, D; Nel, A; Saxon, A	In vivo nasal challenge with diesel exhaust particles enhances expression of the CC chemokines rantes, MIP-1 alpha, and MCP-3 in humans		CLINICAL IMMUNOLOGY	diesel; pollution; chemokines; allergy; inflammation	IN-VIVO; MESSENGER-RNA; ALLERGIC INFLAMMATION; CYTOKINE PRODUCTION; MONONUCLEAR-CELLS; RAGWEED ALLERGEN; IGE PRODUCTION; RESPONSES; EOTAXIN; EOSINOPHILS	Diesel exhaust particles (DEP) enhance allergic inflammation by increasing in vivo IgE and cytokine production in the human upper respiratory mucosa. CC chemokines have been shown to play an important role in inflammation. We examined whether DEP could alter the production of CC chemokines by cells residing in the human nasal mucosa. At both 6 and 24 h following intranasal DEP challenge, the levels of nasal RANTES, MIP-1 alpha, and MCP-3 were significantly elevated compared to baseline. In contrast, DEP did not enhance levels of Eotaxin at any time, demonstrating that the action of DEP was not simply a global effect on all CC chemokines. Challenge with saline resulted in no significant change in expression of any chemokine at any time. Challenge with DEP also resulted in an increase in total cell counts in nasal lavage fluids. Increases in lymphocyte, monocyte/macrophage, and neutrophil cells were observed but there was no change in eosinophil cell numbers. In contrast, there was a significant enhancement of ECP protein levels in washes performed 6 to 24 h after DEP challenge. Elevated specific nasal chemokine expression following exposure to DEP likely participates in the inflammation, cellular infiltration, and increase in IgE observed in the absence of allergen. (C) 2000 Academic Press.	29	71	2000	6	10.1006/clim.2000.4921	Immunology
Risk of childhood asthma and allergic rhinitis in relation to pregnancy complications. Background: Events occurring during Fetal life may affect the development of the immune and respiratory systems and increase the risk of asthma and allergic diseases. Objectives: We sought to elaborate the relations between the occurrence of pregnancy complications and other pregnancy-related conditions and the risk of bronchial obstruction during the first 2 years of life and the occurrence of asthma and allergic rhinitis by the age of 4 years. Pregnancy complications were considered both as predictors of the health outcomes and as possible effects caused by other prenatal factors. Methods: A population-based, l-year, cohort study was carried out involving 2531 children horn in Oslo, Norway. We collected information on maternally related (hyperemesis, hypertension, and preeclampsia) and uterus-related complications in pregnancy (antepartum hemorrhage, preterm contractions, insufficient placenta, and restricted growth of the uterus) and the child's health and environmental exposures at birth and at 6, 12, 18, and 24 months and 4 years of age. The outcomes of interest were bronchial obstruction during the first 2 years and asthma and allergic rhinitis at the age of 4 years. Results: In a logistic regression analysis adjusting for potential confounders, uterus-related, but not other pregnancy-related, complications increased the risk of bronchial obstruction (odds ratio [OR], 2.1; 95% confidence interval [CI], 1,3-3.4), asthma (OR, 3.0; 95% CI, 1.8-5.4), and allergic rhinitis (OR, 2.9; 95% CI, 1.6-5.2). These relations were similar in children of atopic and nonatopic parents. Conclusions: Uterus-related complications in pregnancy increase the risk of having asthma and allergic rhinitis in childhood.. pregnancy complications| prenatal conditions| asthma| allergic rhinitis| childhood|atopic disease| maternal smoking| early-life| infections| children| illness| cohort.	NOV-2000	pregnancy complications| prenatal conditions| asthma| allergic rhinitis| childhood|atopic disease| maternal smoking| early-life| infections| children| illness| cohort	Nafstad, P; Magnus, P; Jaakkola, JJK	Risk of childhood asthma and allergic rhinitis in relation to pregnancy complications		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	pregnancy complications; prenatal conditions; asthma; allergic rhinitis; childhood	ATOPIC DISEASE; MATERNAL SMOKING; EARLY-LIFE; INFECTIONS; CHILDREN; ILLNESS; COHORT	Background: Events occurring during Fetal life may affect the development of the immune and respiratory systems and increase the risk of asthma and allergic diseases. Objectives: We sought to elaborate the relations between the occurrence of pregnancy complications and other pregnancy-related conditions and the risk of bronchial obstruction during the first 2 years of life and the occurrence of asthma and allergic rhinitis by the age of 4 years. Pregnancy complications were considered both as predictors of the health outcomes and as possible effects caused by other prenatal factors. Methods: A population-based, l-year, cohort study was carried out involving 2531 children horn in Oslo, Norway. We collected information on maternally related (hyperemesis, hypertension, and preeclampsia) and uterus-related complications in pregnancy (antepartum hemorrhage, preterm contractions, insufficient placenta, and restricted growth of the uterus) and the child's health and environmental exposures at birth and at 6, 12, 18, and 24 months and 4 years of age. The outcomes of interest were bronchial obstruction during the first 2 years and asthma and allergic rhinitis at the age of 4 years. Results: In a logistic regression analysis adjusting for potential confounders, uterus-related, but not other pregnancy-related, complications increased the risk of bronchial obstruction (odds ratio [OR], 2.1; 95% confidence interval [CI], 1,3-3.4), asthma (OR, 3.0; 95% CI, 1.8-5.4), and allergic rhinitis (OR, 2.9; 95% CI, 1.6-5.2). These relations were similar in children of atopic and nonatopic parents. Conclusions: Uterus-related complications in pregnancy increase the risk of having asthma and allergic rhinitis in childhood.	27	71	2000	7	10.1067/mai.2000.110558	Allergy; Immunology
"Human skin absorption and metabolism of the contact allergens, cinnamic aldehyde, and cinnamic alcohol. trans-Cinnamaldehyde and trans-cinnamic alcohol have been commonly reported to cause allergic contact dermatitis (ACD) in humans. Cinnamaldehyde is a more potent skin sensitizer than cinnamic alcohol. It has been hypothesized that cinnamic alcohol is a ""prohapten"" that requires metabolic activation, presumably by oxidoreductase enzymes such as alcohol dehydrogenase (ADH) or cytochrome P450 2E1 (CYP2E1), to the protein-reactive cinnamaldehyde (a hapten). In this study, the in vitro percutaneous absorption and metabolism of cinnamaldehyde and cinnamic alcohol (78 mu mol dose) has been examined using freshly excised, metabolically viable, full-thickness breast and abdomen skin from six female donors. Penetration rates and total cumulative recoveries of cinnamic compounds that were present in receptor fluid, extracted from within the skin, evaporated from the skin surface, or remained unabsorbed on the skin surface after 24 h were quantified by reversed-phase high-performance liquid chromatography. Biotransformation of cinnamaldehyde to both cinnamic alcohol and cinnamic acid was observed. Topically applied cinnamic alcohol was converted to cinnamaldehyde (found on the skin surface only) and cinnamic acid. To establish whether these biotransformations were enzymatic, experiments were performed in the absence and presence of varying concentrations (80-320 mu mol) of the ADH/CYP2E1 inhibitors pyrazole: or 4-methylpyrazole. The observation that pyrazole significantly reduced (p < 0.05) the total penetration of cinnamic metabolites into receptor fluid, following either cinnamaldehyde or cinnamic alcohol treatment, but did not significantly affect parent chemical penetration, suggests that we are measuring cutaneous metabolic products of ADH activity. The skin absorption and metabolism of cinnamaldehyde and cinnamic alcohol will play an important role in the manifestation of ACD following topical exposure to these compounds. (C) 2000 Academic Press.. cinnamic aldehyde| alcohol| acid| human| skin| metabolism| absorption| pyrazole| dehydrogenase| enzyme|glutathione s-transferases| dehydrogenase gene family| european standard series| percutaneous-absorption| rat skin| fragrance materials| benzyl acetate| sensitization| dermatitis| cinnamaldehyde."	NOV 1-2000	cinnamic aldehyde| alcohol| acid| human| skin| metabolism| absorption| pyrazole| dehydrogenase| enzyme|glutathione s-transferases| dehydrogenase gene family| european standard series| percutaneous-absorption| rat skin| fragrance materials| benzyl acetate| sensitization| dermatitis| cinnamaldehyde	Smith, CK; Moore, CA; Elahi, EN; Smart, ATS; Hotchkiss, SAM	Human skin absorption and metabolism of the contact allergens, cinnamic aldehyde, and cinnamic alcohol		TOXICOLOGY AND APPLIED PHARMACOLOGY	cinnamic aldehyde; alcohol; acid; human; skin; metabolism; absorption; pyrazole; dehydrogenase; enzyme	GLUTATHIONE S-TRANSFERASES; DEHYDROGENASE GENE FAMILY; EUROPEAN STANDARD SERIES; PERCUTANEOUS-ABSORPTION; RAT SKIN; FRAGRANCE MATERIALS; BENZYL ACETATE; SENSITIZATION; DERMATITIS; CINNAMALDEHYDE	"trans-Cinnamaldehyde and trans-cinnamic alcohol have been commonly reported to cause allergic contact dermatitis (ACD) in humans. Cinnamaldehyde is a more potent skin sensitizer than cinnamic alcohol. It has been hypothesized that cinnamic alcohol is a ""prohapten"" that requires metabolic activation, presumably by oxidoreductase enzymes such as alcohol dehydrogenase (ADH) or cytochrome P450 2E1 (CYP2E1), to the protein-reactive cinnamaldehyde (a hapten). In this study, the in vitro percutaneous absorption and metabolism of cinnamaldehyde and cinnamic alcohol (78 mu mol dose) has been examined using freshly excised, metabolically viable, full-thickness breast and abdomen skin from six female donors. Penetration rates and total cumulative recoveries of cinnamic compounds that were present in receptor fluid, extracted from within the skin, evaporated from the skin surface, or remained unabsorbed on the skin surface after 24 h were quantified by reversed-phase high-performance liquid chromatography. Biotransformation of cinnamaldehyde to both cinnamic alcohol and cinnamic acid was observed. Topically applied cinnamic alcohol was converted to cinnamaldehyde (found on the skin surface only) and cinnamic acid. To establish whether these biotransformations were enzymatic, experiments were performed in the absence and presence of varying concentrations (80-320 mu mol) of the ADH/CYP2E1 inhibitors pyrazole: or 4-methylpyrazole. The observation that pyrazole significantly reduced (p < 0.05) the total penetration of cinnamic metabolites into receptor fluid, following either cinnamaldehyde or cinnamic alcohol treatment, but did not significantly affect parent chemical penetration, suggests that we are measuring cutaneous metabolic products of ADH activity. The skin absorption and metabolism of cinnamaldehyde and cinnamic alcohol will play an important role in the manifestation of ACD following topical exposure to these compounds. (C) 2000 Academic Press."	52	71	2000	11	10.1006/taap.2000.9025	Pharmacology & Pharmacy; Toxicology
Transplacental priming of the human immune system with environmental allergens can occur early in gestation. Background: Allergen-specific T cells play an important role in the allergic immune response to various environmental allergens. In vitro studies have shown that T-cell responses to these allergens do occur prenatally. Some allergens (milk proteins) appear to lead more often to fetal T-cell priming than others (house dust mite allergen, ovalbumin, and birch and grass pollen allergens). Objective: We sought to determine the window of opportunity for prenatal T-cell priming with inhalant and nutritive allergens. Methods: The T-cell reactivity of cord blood cells derived through cordocentesis from unborn (n = 62) and term babies (n = 114) in response to inhalant allergens (birch pollen major allergen, recombinant Bet v 1, and timothy grass major allergen, recombinant Phl p 1) was investigated. Results: The results demonstrate that allergen-specific T-cell reactivity is as common in preterm as in term infants (Bet v 1, 8% and 5%, respectively; Phl p 1, 20% and 25%, respectively). Conclusions: Our data support the hypothesis that differential handling of the allergenic proteins by the feto-placental barrier and possibly by antigen-presenting cells may directly modulate the ensuing T-cell immune response.. cord blood cells| allergen| t-cell proliferation| diaplacentral transfer| sensitization|cell proliferative responses| blood mononuclear-cells| respiratory-tract| dendritic cells| birch-pollen| t-cells| antigens| memory| immunization| tolerance.	SEP-2000	cord blood cells| allergen| t-cell proliferation| diaplacentral transfer| sensitization|cell proliferative responses| blood mononuclear-cells| respiratory-tract| dendritic cells| birch-pollen| t-cells| antigens| memory| immunization| tolerance	Szepfalusi, Z; Pichler, J; Elsasser, S; van Duren, K; Ebner, C; Bernaschek, G; Urbanek, R	Transplacental priming of the human immune system with environmental allergens can occur early in gestation		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	cord blood cells; allergen; T-cell proliferation; diaplacentral transfer; sensitization	CELL PROLIFERATIVE RESPONSES; BLOOD MONONUCLEAR-CELLS; RESPIRATORY-TRACT; DENDRITIC CELLS; BIRCH-POLLEN; T-CELLS; ANTIGENS; MEMORY; IMMUNIZATION; TOLERANCE	Background: Allergen-specific T cells play an important role in the allergic immune response to various environmental allergens. In vitro studies have shown that T-cell responses to these allergens do occur prenatally. Some allergens (milk proteins) appear to lead more often to fetal T-cell priming than others (house dust mite allergen, ovalbumin, and birch and grass pollen allergens). Objective: We sought to determine the window of opportunity for prenatal T-cell priming with inhalant and nutritive allergens. Methods: The T-cell reactivity of cord blood cells derived through cordocentesis from unborn (n = 62) and term babies (n = 114) in response to inhalant allergens (birch pollen major allergen, recombinant Bet v 1, and timothy grass major allergen, recombinant Phl p 1) was investigated. Results: The results demonstrate that allergen-specific T-cell reactivity is as common in preterm as in term infants (Bet v 1, 8% and 5%, respectively; Phl p 1, 20% and 25%, respectively). Conclusions: Our data support the hypothesis that differential handling of the allergenic proteins by the feto-placental barrier and possibly by antigen-presenting cells may directly modulate the ensuing T-cell immune response.	30	71	2000	7		Allergy; Immunology
Prevalence and clinical spectrum of gastroesophageal reflux: A population-based study in Asan-si, Korea. BACKGROUND AND AIMS: This study estimated the prevalence and clinical spectrum of gastroesophageal reflux disease (GERD) in Asan-si, Korea, as the prevalence is believed to be lower than in Western countries. METHODS: A cross-sectional survey, using a reliable and valid questionnaire, was performed on randomly selected 2,240 Asan-si residents aged between 18 and 69 yr. All respondents were interviewed at their homes or offices by a team of interviewers. RESULTS: Of the 1,902 eligible subjects, 1,417 (78.4%: male 762; female 655) were surveyed. The prevalence of heartburn occurring at least once a month, at least once a week, and at least twice a week was 4.71% (95% confidence interval (CI), 3.6-5.8), 2.0% (95% CI, 1.2-2.7), and 1.3% (95% CI, 0.7-1.9), respectively. The corresponding figures for acid regurgitation were 4.4% (95% CI, 3.3-5.5) and 2.0% (95% CI, 1.3-2.8), respectively. The prevalence of GERD, defined as heartburn and/or acid regurgitation experienced at least weekly, was 3.5% (95% CI, 2.6-4.5). No significant difference was detected between sexes. The prevalence of heartburn was associated with increasing age (p < 0.001). Nineteen percent of our population reported at least one of the atypical symptoms, for instance, chest pain, dysphagia, globus sensation, asthma, bronchitis, pneumonia, or hoarseness. The frequency of frequent GERD among subjects reporting any of the atypical symptoms was 12.6%, which was higher than that of the subjects without atypical symptoms. Patients with typical reflux symptoms were more common among those with atypical symptoms, compared to those without such symptoms (p < 0.001). Using a logistic regression model after adjusting for age and sex, typical reflux symptoms were associated with chest pain (odds ratio (OR), 9.3; 95% CI, 5.9-14.7), dysphagia (OR, 6.4; 95% CI, 2.8-14.7), globus sensation (OR, 3.9; 95% CI, 1.5-9.7), hoarseness (OR, 4.3; 95% CI, 1.4-13.1), asthma (OR, 2.6; 95% CI, 1.4-4.8), and bronchitis (OR, 1.2; 95% CI, 0.6-2.3). CONCLUSION: The prevalence of GERD was 3.5% in this Korean population. Heartburn and acid regurgitation were significantly associated with chest pain, dysphagia, globus sensation, hoarseness, and asthma.. helicobacter-pylori infection| gastric-acid-secretion| duodenal-ulcer| disease| symptoms| esophagitis| questionnaire| validation| chinese.	APR-2005	helicobacter-pylori infection| gastric-acid-secretion| duodenal-ulcer| disease| symptoms| esophagitis| questionnaire| validation| chinese	Cho, YS; Choi, MG; Jeong, JJ; Chung, WC; Lee, IS; Kim, SW; Han, SW; Choi, KY; Chung, IS	Prevalence and clinical spectrum of gastroesophageal reflux: A population-based study in Asan-si, Korea		AMERICAN JOURNAL OF GASTROENTEROLOGY		HELICOBACTER-PYLORI INFECTION; GASTRIC-ACID-SECRETION; DUODENAL-ULCER; DISEASE; SYMPTOMS; ESOPHAGITIS; QUESTIONNAIRE; VALIDATION; CHINESE	BACKGROUND AND AIMS: This study estimated the prevalence and clinical spectrum of gastroesophageal reflux disease (GERD) in Asan-si, Korea, as the prevalence is believed to be lower than in Western countries. METHODS: A cross-sectional survey, using a reliable and valid questionnaire, was performed on randomly selected 2,240 Asan-si residents aged between 18 and 69 yr. All respondents were interviewed at their homes or offices by a team of interviewers. RESULTS: Of the 1,902 eligible subjects, 1,417 (78.4%: male 762; female 655) were surveyed. The prevalence of heartburn occurring at least once a month, at least once a week, and at least twice a week was 4.71% (95% confidence interval (CI), 3.6-5.8), 2.0% (95% CI, 1.2-2.7), and 1.3% (95% CI, 0.7-1.9), respectively. The corresponding figures for acid regurgitation were 4.4% (95% CI, 3.3-5.5) and 2.0% (95% CI, 1.3-2.8), respectively. The prevalence of GERD, defined as heartburn and/or acid regurgitation experienced at least weekly, was 3.5% (95% CI, 2.6-4.5). No significant difference was detected between sexes. The prevalence of heartburn was associated with increasing age (p < 0.001). Nineteen percent of our population reported at least one of the atypical symptoms, for instance, chest pain, dysphagia, globus sensation, asthma, bronchitis, pneumonia, or hoarseness. The frequency of frequent GERD among subjects reporting any of the atypical symptoms was 12.6%, which was higher than that of the subjects without atypical symptoms. Patients with typical reflux symptoms were more common among those with atypical symptoms, compared to those without such symptoms (p < 0.001). Using a logistic regression model after adjusting for age and sex, typical reflux symptoms were associated with chest pain (odds ratio (OR), 9.3; 95% CI, 5.9-14.7), dysphagia (OR, 6.4; 95% CI, 2.8-14.7), globus sensation (OR, 3.9; 95% CI, 1.5-9.7), hoarseness (OR, 4.3; 95% CI, 1.4-13.1), asthma (OR, 2.6; 95% CI, 1.4-4.8), and bronchitis (OR, 1.2; 95% CI, 0.6-2.3). CONCLUSION: The prevalence of GERD was 3.5% in this Korean population. Heartburn and acid regurgitation were significantly associated with chest pain, dysphagia, globus sensation, hoarseness, and asthma.	32	105	2005	7	10.1111/j.1572-0241.2005.41245.x	Gastroenterology & Hepatology
Nonredundant function of phosphodiesterases 4D and 4B in neutrophil recruitment to the site of inflammation. Neutrophils have been implicated in the pathogenesis of many inflammatory lung diseases, including chronic obstructive pulmonary disease and asthma. With this study, we investigated how disruption of cAMP signaling impacts the function of neutrophil recruitment to the lung. Four genes code for type 4 phosphodiesterases (PDE4s), enzymes critical for regulation of cAMP levels and cell signaling. Ablation of two of these genes, PDE4B and PDE4D, but not PDE4A, has profound effects on neutrophil function. In a paradigm of mouse lung injury induced by endotoxin inhalation, the number of neutrophils recovered in the bronchoalveolar lavage was markedly decreased in PDE4D(-/-) and PDE4B(-/-) mice 4 and 24 h after exposure to LPS. Acute PDE4 inhibition with rolipram had additional inhibitory effects on nentrophil migration in PDE4B(-/-) and, to a lesser extent, PDE4D(-/-) mice. This decreased neutrophil recruitment occurred without major changes in chemokine accumulation in bronchoalveolar lavage, suggesting a dysfunction intrinsic to neutrophils. This hypothesis was confirmed by investigating the expression of adhesion molecules on the surface of neutrophils and chemotaxis in vitro. CD18 expression was decreased after ablation of both PDE4B and PDE4D, whereas CD11 expression was not significantly affected. Chemotaxis in response to KC and macrophage inflammatory protein-2 was markedly reduced in PDE4B(-/-) and PDE4D(-/-) neutrophils. The effect of PDE4 ablation on chemotaxis was comparable, but not additive, to the effects of acute PDE4 inhibition with rolipram. These data demonstrate that PDE4B and PDE4D play complementary, but not redundant, roles in the control of neutrophil function.. cyclic adenosine-monophosphate| necrosis-factor-alpha| protein-kinase-a| t-cell-activation| leukocyte adhesion| intracellular camp| pde4 inhibitors| beta-arrestins| tnf-alpha| amp.	DEC 15-2004	cyclic adenosine-monophosphate| necrosis-factor-alpha| protein-kinase-a| t-cell-activation| leukocyte adhesion| intracellular camp| pde4 inhibitors| beta-arrestins| tnf-alpha| amp	Ariga, M; Neitzert, B; Nakae, S; Mottin, G; Bertrand, C; Pruniaux, MP; Jin, SLC; Conti, M	Nonredundant function of phosphodiesterases 4D and 4B in neutrophil recruitment to the site of inflammation		JOURNAL OF IMMUNOLOGY		CYCLIC ADENOSINE-MONOPHOSPHATE; NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE-A; T-CELL-ACTIVATION; LEUKOCYTE ADHESION; INTRACELLULAR CAMP; PDE4 INHIBITORS; BETA-ARRESTINS; TNF-ALPHA; AMP	Neutrophils have been implicated in the pathogenesis of many inflammatory lung diseases, including chronic obstructive pulmonary disease and asthma. With this study, we investigated how disruption of cAMP signaling impacts the function of neutrophil recruitment to the lung. Four genes code for type 4 phosphodiesterases (PDE4s), enzymes critical for regulation of cAMP levels and cell signaling. Ablation of two of these genes, PDE4B and PDE4D, but not PDE4A, has profound effects on neutrophil function. In a paradigm of mouse lung injury induced by endotoxin inhalation, the number of neutrophils recovered in the bronchoalveolar lavage was markedly decreased in PDE4D(-/-) and PDE4B(-/-) mice 4 and 24 h after exposure to LPS. Acute PDE4 inhibition with rolipram had additional inhibitory effects on nentrophil migration in PDE4B(-/-) and, to a lesser extent, PDE4D(-/-) mice. This decreased neutrophil recruitment occurred without major changes in chemokine accumulation in bronchoalveolar lavage, suggesting a dysfunction intrinsic to neutrophils. This hypothesis was confirmed by investigating the expression of adhesion molecules on the surface of neutrophils and chemotaxis in vitro. CD18 expression was decreased after ablation of both PDE4B and PDE4D, whereas CD11 expression was not significantly affected. Chemotaxis in response to KC and macrophage inflammatory protein-2 was markedly reduced in PDE4B(-/-) and PDE4D(-/-) neutrophils. The effect of PDE4 ablation on chemotaxis was comparable, but not additive, to the effects of acute PDE4 inhibition with rolipram. These data demonstrate that PDE4B and PDE4D play complementary, but not redundant, roles in the control of neutrophil function.	58	105	2004	8		Immunology
The role of toll-like receptor 4 in environmental airway injury in mice. Inhalation of toxins commonly found in air pollution contributes to the development and progression of asthma and environmental airway injury. In this study, we investigated the requirement of toll-like receptor 4 (TLR4) in mice for pulmonary responses to three environmental toxins: aerosolized lipopolysaccharide, particulate matter (residual oil fly ash), and ozone. The physiologic and biologic responses to these toxins were evaluated by the extent of airway responsiveness, neutrophil recruitment to the lower respiratory tract, changes in inflammatory cytokines, and the concentration of protein in the lavage fluid. Genetically engineered, TLR4-deficient mice (C57BL/6(TLR4-/-)) were unresponsive to inhaled lipopolysaccharide, except for minimal increases in some inflammatory cytokines. In contrast, C57BL/6(TLR4-/-) mice did not differ from wild-type mice in their airway response to instilled residual oil fly ash or acute ozone exposure; however, we found that, despite a robust inflammatory response, C57BL/6(TLR4-/-) mice are protected against the development of airway hyperresponsiveness after subchronic ozone exposure. These data demonstrate in the mouse that the requirement of TLR4 for pulmonary inflammation depends on the nature of the toxin and appears specific to toxin and exposure conditions.. toll-like receptor| innate immunity| endotoxin| ozone| residual oil fly ash|oil fly-ash| induced lung inflammation| 18-20 h postexposure| grain dust| alveolar macrophages| pollution particles| cytokine production| epithelial-cells| ozone exposure| cutting edge.	JUL 15-2004	toll-like receptor| innate immunity| endotoxin| ozone| residual oil fly ash|oil fly-ash| induced lung inflammation| 18-20 h postexposure| grain dust| alveolar macrophages| pollution particles| cytokine production| epithelial-cells| ozone exposure| cutting edge	Hollingsworth, JW; Cook, DN; Brass, DM; Walker, JKL; Morgan, DL; Foster, WM; Schwartz, DA	The role of toll-like receptor 4 in environmental airway injury in mice		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	toll-like receptor; innate immunity; endotoxin; ozone; residual oil fly ash	OIL FLY-ASH; INDUCED LUNG INFLAMMATION; 18-20 H POSTEXPOSURE; GRAIN DUST; ALVEOLAR MACROPHAGES; POLLUTION PARTICLES; CYTOKINE PRODUCTION; EPITHELIAL-CELLS; OZONE EXPOSURE; CUTTING EDGE	Inhalation of toxins commonly found in air pollution contributes to the development and progression of asthma and environmental airway injury. In this study, we investigated the requirement of toll-like receptor 4 (TLR4) in mice for pulmonary responses to three environmental toxins: aerosolized lipopolysaccharide, particulate matter (residual oil fly ash), and ozone. The physiologic and biologic responses to these toxins were evaluated by the extent of airway responsiveness, neutrophil recruitment to the lower respiratory tract, changes in inflammatory cytokines, and the concentration of protein in the lavage fluid. Genetically engineered, TLR4-deficient mice (C57BL/6(TLR4-/-)) were unresponsive to inhaled lipopolysaccharide, except for minimal increases in some inflammatory cytokines. In contrast, C57BL/6(TLR4-/-) mice did not differ from wild-type mice in their airway response to instilled residual oil fly ash or acute ozone exposure; however, we found that, despite a robust inflammatory response, C57BL/6(TLR4-/-) mice are protected against the development of airway hyperresponsiveness after subchronic ozone exposure. These data demonstrate in the mouse that the requirement of TLR4 for pulmonary inflammation depends on the nature of the toxin and appears specific to toxin and exposure conditions.	51	105	2004	7	10.1164/rccm.200311-1499OC	General & Internal Medicine; Respiratory System
'Entopy': localized mucosal allergic disease in the absence of systemic responses for atopy. Background The Th2 immune response in the nasal mucosa of subjects with allergic rhinitis is mediated by allergen-specific IgE. Moreover, these subjects show positive responses for markers of systemic atopy, including allergen-specific skin sensitivity and raised serum IgE titres. In contrast, idiopathic rhinitis (IR) subjects with similar histological nasal mucosal features differ in being defined as non-allergic because they have negative atopic responses. Objective We hypothesized that it is possible to have an allergic Th2 disease pathway localized in the nasal mucosa of 'non-allergic' rhinitis subjects despite an absence of atopic responses. Methods The presence of house dust mite and grass pollen-specific IgE antibodies was investigated in non-atopic ( n=10) and atopic ( n=11) subjects with persistent rhinitis and compared to normal ( n=12) control subjects. Biotin-labelled allergen was used to localize specific allergen-binding antibodies in situ in sections of nasal mucosa. Results Grass pollen allergen binding was detected in the nasal mucosa of 3/10 non-atopic IR subjects but, in contrast, dust mite-specific antibodies were not detected. Specific antibodies were present in a total of 8/11 mucosal samples from the allergic group, but none was detected in normal control tissues. Conclusion These findings support the concept of localized nasal allergy in 'non-atopic' rhinitis subjects. We propose the term 'entopy' to define this phenomenon and believe that this concept has a wider implication for localized allergic responses in other mucosal sites.. atopy| idiopathic| ige| inflammation| mast cells| nasal mucosa| rhinitis|idiopathic rhinitis| nasal-mucosa| serum ige| b-cells| skin| provocation| expression| antibodies.	OCT-2003	atopy| idiopathic| ige| inflammation| mast cells| nasal mucosa| rhinitis|idiopathic rhinitis| nasal-mucosa| serum ige| b-cells| skin| provocation| expression| antibodies	Powe, DG; Jagger, C; Kleinjan, A; Carney, AS; Jenkins, D; Jones, NS	'Entopy': localized mucosal allergic disease in the absence of systemic responses for atopy		CLINICAL AND EXPERIMENTAL ALLERGY	atopy; idiopathic; IgE; inflammation; mast cells; nasal mucosa; rhinitis	IDIOPATHIC RHINITIS; NASAL-MUCOSA; SERUM IGE; B-CELLS; SKIN; PROVOCATION; EXPRESSION; ANTIBODIES	Background The Th2 immune response in the nasal mucosa of subjects with allergic rhinitis is mediated by allergen-specific IgE. Moreover, these subjects show positive responses for markers of systemic atopy, including allergen-specific skin sensitivity and raised serum IgE titres. In contrast, idiopathic rhinitis (IR) subjects with similar histological nasal mucosal features differ in being defined as non-allergic because they have negative atopic responses. Objective We hypothesized that it is possible to have an allergic Th2 disease pathway localized in the nasal mucosa of 'non-allergic' rhinitis subjects despite an absence of atopic responses. Methods The presence of house dust mite and grass pollen-specific IgE antibodies was investigated in non-atopic ( n=10) and atopic ( n=11) subjects with persistent rhinitis and compared to normal ( n=12) control subjects. Biotin-labelled allergen was used to localize specific allergen-binding antibodies in situ in sections of nasal mucosa. Results Grass pollen allergen binding was detected in the nasal mucosa of 3/10 non-atopic IR subjects but, in contrast, dust mite-specific antibodies were not detected. Specific antibodies were present in a total of 8/11 mucosal samples from the allergic group, but none was detected in normal control tissues. Conclusion These findings support the concept of localized nasal allergy in 'non-atopic' rhinitis subjects. We propose the term 'entopy' to define this phenomenon and believe that this concept has a wider implication for localized allergic responses in other mucosal sites.	33	105	2003	6	10.1046/j.1365-2222.2003.01737.x	Allergy; Immunology
TLR4 gene variants modify endotoxin effects on asthma. Background: Environmental exposure to endotoxin might have a crucial role in immune maturation and development of asthma. Objective: The aim of this study was to investigate whether the effect of endotoxin concentration in settled house dust on asthma is modified by the presence of variation in the TLR4 gene. Methods: We performed a cross-sectional study within the German follow-up of the European Community Respiratory Health Survey. Multivariate logistic regression analysis and nonparametric effect estimates (S-Plus) were applied to examine the association between endotoxin exposure and diagnosed asthma, related clinical symptoms, and bronchial hyperreactivity (BHR) stratified for noncarriers and carriers of G299/1399 polymorphism in the TLR4 gene. Results: In the noncarrier group (n = 279), the prevalence of asthma was significantly increased with elevated endotoxin levels in house dust with adjusted odds ratio 6.24 (95% CI, 1.33-29.17) in the second tertile, and 4.54 (95% CI, 0.94-21.96) in the third tertile compared with the lowest endotoxin fertile. The carriers of the polymorphisms (n = 55) showed a nonsignificant trend to have a lower risk of asthma (crude odds ratio, 0.67; 95% CI, 0.06-8.06 for the second tertile and 1.33; 95% CI, 0.17-10.58 for the third tertile). We found a similar association for wheeze and endotoxin exposure that was also attenuated in subjects with G299/1399 polymorphisms. Conclusions: The G299/1399 polymorphisms were associated with a modified response to endotoxin, but the functional relationship still needs clarification.. endotoxin| tlr4| gene polymorphism| asthma| ecrhs|house-dust endotoxin| toll-like receptor-4| innate immunity| inhaled lipopolysaccharide| respiratory symptoms| european-community| exposure| children| cd14| hyperresponsiveness.	AUG-2003	endotoxin| tlr4| gene polymorphism| asthma| ecrhs|house-dust endotoxin| toll-like receptor-4| innate immunity| inhaled lipopolysaccharide| respiratory symptoms| european-community| exposure| children| cd14| hyperresponsiveness	Werner, M; Topp, R; Wimmer, K; Richter, K; Bischof, W; Wjst, M; Heinrich, J	TLR4 gene variants modify endotoxin effects on asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	endotoxin; TLR4; gene polymorphism; asthma; ECRHS	HOUSE-DUST ENDOTOXIN; TOLL-LIKE RECEPTOR-4; INNATE IMMUNITY; INHALED LIPOPOLYSACCHARIDE; RESPIRATORY SYMPTOMS; EUROPEAN-COMMUNITY; EXPOSURE; CHILDREN; CD14; HYPERRESPONSIVENESS	Background: Environmental exposure to endotoxin might have a crucial role in immune maturation and development of asthma. Objective: The aim of this study was to investigate whether the effect of endotoxin concentration in settled house dust on asthma is modified by the presence of variation in the TLR4 gene. Methods: We performed a cross-sectional study within the German follow-up of the European Community Respiratory Health Survey. Multivariate logistic regression analysis and nonparametric effect estimates (S-Plus) were applied to examine the association between endotoxin exposure and diagnosed asthma, related clinical symptoms, and bronchial hyperreactivity (BHR) stratified for noncarriers and carriers of G299/1399 polymorphism in the TLR4 gene. Results: In the noncarrier group (n = 279), the prevalence of asthma was significantly increased with elevated endotoxin levels in house dust with adjusted odds ratio 6.24 (95% CI, 1.33-29.17) in the second tertile, and 4.54 (95% CI, 0.94-21.96) in the third tertile compared with the lowest endotoxin fertile. The carriers of the polymorphisms (n = 55) showed a nonsignificant trend to have a lower risk of asthma (crude odds ratio, 0.67; 95% CI, 0.06-8.06 for the second tertile and 1.33; 95% CI, 0.17-10.58 for the third tertile). We found a similar association for wheeze and endotoxin exposure that was also attenuated in subjects with G299/1399 polymorphisms. Conclusions: The G299/1399 polymorphisms were associated with a modified response to endotoxin, but the functional relationship still needs clarification.	37	105	2003	8	10.1067/mai.2003.1648	Allergy; Immunology
Improving asthma outcomes and self-management behaviors of inner-city children - A Randomized trial of the health buddy interactive device and an asthma diary. Background: Asthma is an important cause of morbidity, absence from school, and use of health services among children. Computer-based educational programs can be designed to enhance children's self-management skills and to reduce adverse outcomes. Objective: To assess the effectiveness of an interactive device programmed for the management of pediatric asthma. Design: A randomized controlled trial (66 participants were in the intervention group and 68 were in the control group). Setting: Interventions conducted at home and in an outpatient hospital clinic. Participants: Inner-city children aged 8 to 16 years diagnosed as having asthma by a physician. Intervention: An asthma self-management and education program, the Health Buddy, designed to enable children to assess and monitor their asthma symptoms and quality of life and to transmit this information to health care providers (physicians, nurses, or other case managers) through a secure Web site. Control group participants used an asthma diary. Main Outcome Measures: Any limitation in activity was the primary outcome. Secondary outcomes included perceived asthma symptoms, absence from school, any peak flow reading in the yellow or red zone, and use of health services. Results: After adjusting for covariates, the odds of having any limitation in activity during the 90-day trial were significantly (P = .03) lower for children randomized to the Health Buddy. The intervention group also was significantly (P = .01) less likely to report peak flow readings in the yellow or red zone or to make urgent calls to the hospital (P = .05). Self-care behaviors, which were important correlates of asthma outcomes, also improved far more for the intervention group. Conclusion: Compared with the asthma diary, monitoring asthma symptoms and functional status with the Health Buddy increases self-management skills and improves asthma outcomes.. quality-of-life| intervention| education| emergency| computer| program| impact| care| flow.	FEB-2002	quality-of-life| intervention| education| emergency| computer| program| impact| care| flow	Guendelman, S; Meade, K; Benson, M; Chen, YQ; Samuels, S	Improving asthma outcomes and self-management behaviors of inner-city children - A Randomized trial of the health buddy interactive device and an asthma diary		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		QUALITY-OF-LIFE; INTERVENTION; EDUCATION; EMERGENCY; COMPUTER; PROGRAM; IMPACT; CARE; FLOW	Background: Asthma is an important cause of morbidity, absence from school, and use of health services among children. Computer-based educational programs can be designed to enhance children's self-management skills and to reduce adverse outcomes. Objective: To assess the effectiveness of an interactive device programmed for the management of pediatric asthma. Design: A randomized controlled trial (66 participants were in the intervention group and 68 were in the control group). Setting: Interventions conducted at home and in an outpatient hospital clinic. Participants: Inner-city children aged 8 to 16 years diagnosed as having asthma by a physician. Intervention: An asthma self-management and education program, the Health Buddy, designed to enable children to assess and monitor their asthma symptoms and quality of life and to transmit this information to health care providers (physicians, nurses, or other case managers) through a secure Web site. Control group participants used an asthma diary. Main Outcome Measures: Any limitation in activity was the primary outcome. Secondary outcomes included perceived asthma symptoms, absence from school, any peak flow reading in the yellow or red zone, and use of health services. Results: After adjusting for covariates, the odds of having any limitation in activity during the 90-day trial were significantly (P = .03) lower for children randomized to the Health Buddy. The intervention group also was significantly (P = .01) less likely to report peak flow readings in the yellow or red zone or to make urgent calls to the hospital (P = .05). Self-care behaviors, which were important correlates of asthma outcomes, also improved far more for the intervention group. Conclusion: Compared with the asthma diary, monitoring asthma symptoms and functional status with the Health Buddy increases self-management skills and improves asthma outcomes.	25	105	2002	7		Pediatrics
"Peanut and tree nut allergic reactions in restaurants and other food establishments. Background: The clinical features of food-allergic reactions in restaurants and other food establishments have not been studied. Of the registrants in the United States Peanut and Tree Nut Allergy Registry (PAR), 13.7% have reported reactions associated with such establishments. Objective: The purpose of this study was to determine the features of allergic reactions to peanut and tree nut in restaurant foods and foods purchased at other private establishments (eg, ice cream shops and bakeries). Methods: Telephone interviews were conducted through use of a structured questionnaire. Subjects/parental surrogates were randomly selected from among the 706 PAR registrants who reported a reaction in a restaurant or other food establishment. Results: Details were obtained for 156 episodes (29 first-time reactions) from 129 subjects/parental surrogates. Most reactions were caused by peanut (67%) or tree nut (24%); for some reactions (9%), the cause was a combination of peanut and another nut or was unknown. Symptoms began at a median of 5 minutes after exposure and were severe in 27% of reactions. Overall, 86% of reactions were treated (antihistamines, 86%; epinephrine, 40%). Establishments commonly cited were Asian food restaurants (19%), ice cream shops (14%), and bakeries/doughnut shops (13%). Among meal courses, desserts were a common cause (43%). Of 106 registrants with previously diagnosed allergy who ordered food specifically for ingestion by the allergic individual, only 45% gave prior notification about the allergy to the establishment. For 83 (78%) of these 106 reactions, someone in the establishment knew that the food contained peanut or tree nut as an ingredient; in 50% of these incidents, the food item was ""hidden"" (in sauces, dressings, egg rolls, etc), visual identification being prevented. In 23 (22%) of the 106 cases, exposures were reported from contamination caused primarily by shared cooking/serving supplies. In the remaining 21 subjects with previously diagnosed allergy, reactions resulted from ingestion of food not intended for them, ingestion of food selected from buffet/food bars, or skin contact/inhalation (residual food on tables, 2; peanut shells covering floors, 2; being within 2 feet of the cooking of the food, 1). Conclusions: Restaurants and other food establishments pose a number of dangers for peanut- and tree nut-allergic individuals, particularly with respect to cross-contamination and unexpected ingredients in desserts and Asian food. Failure to establish a clear line of communication between patron and establishment is a frequent cause of errors.. peanut| tree nut| allergy| restaurant."	NOV-2001	peanut| tree nut| allergy| restaurant	Furlong, TJ; DeSimone, J; Sicherer, SH	Peanut and tree nut allergic reactions in restaurants and other food establishments		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	peanut; tree nut; allergy; restaurant		"Background: The clinical features of food-allergic reactions in restaurants and other food establishments have not been studied. Of the registrants in the United States Peanut and Tree Nut Allergy Registry (PAR), 13.7% have reported reactions associated with such establishments. Objective: The purpose of this study was to determine the features of allergic reactions to peanut and tree nut in restaurant foods and foods purchased at other private establishments (eg, ice cream shops and bakeries). Methods: Telephone interviews were conducted through use of a structured questionnaire. Subjects/parental surrogates were randomly selected from among the 706 PAR registrants who reported a reaction in a restaurant or other food establishment. Results: Details were obtained for 156 episodes (29 first-time reactions) from 129 subjects/parental surrogates. Most reactions were caused by peanut (67%) or tree nut (24%); for some reactions (9%), the cause was a combination of peanut and another nut or was unknown. Symptoms began at a median of 5 minutes after exposure and were severe in 27% of reactions. Overall, 86% of reactions were treated (antihistamines, 86%; epinephrine, 40%). Establishments commonly cited were Asian food restaurants (19%), ice cream shops (14%), and bakeries/doughnut shops (13%). Among meal courses, desserts were a common cause (43%). Of 106 registrants with previously diagnosed allergy who ordered food specifically for ingestion by the allergic individual, only 45% gave prior notification about the allergy to the establishment. For 83 (78%) of these 106 reactions, someone in the establishment knew that the food contained peanut or tree nut as an ingredient; in 50% of these incidents, the food item was ""hidden"" (in sauces, dressings, egg rolls, etc), visual identification being prevented. In 23 (22%) of the 106 cases, exposures were reported from contamination caused primarily by shared cooking/serving supplies. In the remaining 21 subjects with previously diagnosed allergy, reactions resulted from ingestion of food not intended for them, ingestion of food selected from buffet/food bars, or skin contact/inhalation (residual food on tables, 2; peanut shells covering floors, 2; being within 2 feet of the cooking of the food, 1). Conclusions: Restaurants and other food establishments pose a number of dangers for peanut- and tree nut-allergic individuals, particularly with respect to cross-contamination and unexpected ingredients in desserts and Asian food. Failure to establish a clear line of communication between patron and establishment is a frequent cause of errors."	10	105	2001	4		Allergy; Immunology
Efficacy of sublingual immunotherapy in children with asthma and rhinitis: A double-blind, placebo-controlled study. To evaluate the efficacy of specific sublingual immunotherapy (SLIT), we enrolled 15 children with asthma and rhinitis (7 girls, 8 boys, mean +/- SD age of 11.7 +/- 3.3) allergic to house dust mite (HDM) into a double-blind, placebo-controlled study. After a run-in period, patients were randomized to receive either placebo (n = 7) or SLIT (n = 8) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus) + Dermatophagoides farinea (D. farinea) 50/50 extract. They received increasing doses up to 100 index units of reactivity (IR) every day for 4 weeks, then 100 IR/day for another 4 weeks, followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months. Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores, serum total IgE levels, results of lung function tests, methacholine provocation tests, and skin prick tests. Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group (P = 0.05, P = 0.028, respectively), whereas no such difference was observed in the placebo group. At the end of follow-up, mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group (P = 0.04). Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups, whereas end-point wheal diameter obtained with D.pteronyssinus extract was significantly less in the SLIT vs. the placebo group (p = 0.026). At the end of 6 months, peak expiratory flow (PEF) values in the placebo group was significantly lower than in the SLIT group (P = 0.049). Throughout the treatment period, the SLIT group was found to have less asthma exacerbations than the placebo group (p = 0.007). The provocation concentration causing a 20% drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups. None of the patients reported local or systemic side effects from SLIT. Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM. (C) 2001 Wiley-Liss, Inc.. sublingual immunotherapy| asthma| rhinitis| house dust mite| children|house-dust-mite| dermatophagoides-pteronyssinus| pollen extract| trial| slit.	JUL-2001	sublingual immunotherapy| asthma| rhinitis| house dust mite| children|house-dust-mite| dermatophagoides-pteronyssinus| pollen extract| trial| slit	Bahceciler, NN; Isik, U; Barlan, IB; Basaran, MM	Efficacy of sublingual immunotherapy in children with asthma and rhinitis: A double-blind, placebo-controlled study		PEDIATRIC PULMONOLOGY	sublingual immunotherapy; asthma; rhinitis; house dust mite; children	HOUSE-DUST-MITE; DERMATOPHAGOIDES-PTERONYSSINUS; POLLEN EXTRACT; TRIAL; SLIT	To evaluate the efficacy of specific sublingual immunotherapy (SLIT), we enrolled 15 children with asthma and rhinitis (7 girls, 8 boys, mean +/- SD age of 11.7 +/- 3.3) allergic to house dust mite (HDM) into a double-blind, placebo-controlled study. After a run-in period, patients were randomized to receive either placebo (n = 7) or SLIT (n = 8) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus) + Dermatophagoides farinea (D. farinea) 50/50 extract. They received increasing doses up to 100 index units of reactivity (IR) every day for 4 weeks, then 100 IR/day for another 4 weeks, followed by maintenance therapy consisting of 20 drops 2 times a week for 4 months. Efficacy was assessed at the end of 6 months of therapy according to symptom and medication scores, serum total IgE levels, results of lung function tests, methacholine provocation tests, and skin prick tests. Daily means for the asthma score and use of inhaled beta-2-mimetics decreased significantly in the SLIT group (P = 0.05, P = 0.028, respectively), whereas no such difference was observed in the placebo group. At the end of follow-up, mean daily doses of intranasal steroids needed for control of rhinitis symptoms decreased significantly in the SLIT group (P = 0.04). Baseline skin sensitivity to D. pteronyssinus and D. farinea was not significantly different between in the two groups, whereas end-point wheal diameter obtained with D.pteronyssinus extract was significantly less in the SLIT vs. the placebo group (p = 0.026). At the end of 6 months, peak expiratory flow (PEF) values in the placebo group was significantly lower than in the SLIT group (P = 0.049). Throughout the treatment period, the SLIT group was found to have less asthma exacerbations than the placebo group (p = 0.007). The provocation concentration causing a 20% drop in forced expired volume in 1 sec did not change throughout the treatment period in either groups. None of the patients reported local or systemic side effects from SLIT. Results of this study suggests that SLIT may be a useful alternative or additional therapy in the treatment of children with asthma/rhinitis due to HDM. (C) 2001 Wiley-Liss, Inc.	21	105	2001	7	10.1002/ppul.1088	Pediatrics; Respiratory System
Carbon monoxide attenuates aero allergen-induced inflammation in mice. Carbon monoxide (CO) generated by catalysis of heme by heme oxygenase is increased in the exhaled air of asthmatic patients. Based on recent studies demonstrating that asthma is an inflammatory disease associated with increased oxidants and that CO confers cytoprotection in oxidant-induced lung injury and inflammation, we sought to better understand the functional role of CO in asthma by using an aeroallergen model. Mice were sensitized to ovalbumin, challenged with aerosolized ovalbumin, and maintained in either CO (250 parts/million) or room air for 48 h. The differential effects of CO on bronchoalveolar lavage (BAL) fluid cell types were observed, with a marked attenuation of BAL fluid eosinophils in the CO-treated animals at 24 and 48 h. A marked reduction of the proinflammatory cytokine interleukin-5 was observed in the CO-treated mice, with no significant changes for other proinflammatory cytokines. These differential Effects of CO were also observed with leukotrienes (LTs) and prostaglandins in that CO significantly decreased BAL fluid PGE(2), and LTB4 but exerted negligible effect on thromboxane B-2 or LTC4/D-4/E-4. Our data suggest a putative immunoregulatory role for CO in aeroallergen-induced inflammation in mice.. heme oxygenase| asthma| eosinophils| ovalbumin| cytokines|hyperoxic lung injury| cytokine messenger-rna| murine model| airway hyperresponsiveness| bronchoalveolar lavage| bronchial hyperresponsiveness| eosinophilic inflammation| pulmonary inflammation| heme oxygenase-1| oxidative stress.	JUL-2001	heme oxygenase| asthma| eosinophils| ovalbumin| cytokines|hyperoxic lung injury| cytokine messenger-rna| murine model| airway hyperresponsiveness| bronchoalveolar lavage| bronchial hyperresponsiveness| eosinophilic inflammation| pulmonary inflammation| heme oxygenase-1| oxidative stress	Chapman, JT; Otterbein, LE; Elias, JA; Choi, AMK	Carbon monoxide attenuates aero allergen-induced inflammation in mice		AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY	heme oxygenase; asthma; eosinophils; ovalbumin; cytokines	HYPEROXIC LUNG INJURY; CYTOKINE MESSENGER-RNA; MURINE MODEL; AIRWAY HYPERRESPONSIVENESS; BRONCHOALVEOLAR LAVAGE; BRONCHIAL HYPERRESPONSIVENESS; EOSINOPHILIC INFLAMMATION; PULMONARY INFLAMMATION; HEME OXYGENASE-1; OXIDATIVE STRESS	Carbon monoxide (CO) generated by catalysis of heme by heme oxygenase is increased in the exhaled air of asthmatic patients. Based on recent studies demonstrating that asthma is an inflammatory disease associated with increased oxidants and that CO confers cytoprotection in oxidant-induced lung injury and inflammation, we sought to better understand the functional role of CO in asthma by using an aeroallergen model. Mice were sensitized to ovalbumin, challenged with aerosolized ovalbumin, and maintained in either CO (250 parts/million) or room air for 48 h. The differential effects of CO on bronchoalveolar lavage (BAL) fluid cell types were observed, with a marked attenuation of BAL fluid eosinophils in the CO-treated animals at 24 and 48 h. A marked reduction of the proinflammatory cytokine interleukin-5 was observed in the CO-treated mice, with no significant changes for other proinflammatory cytokines. These differential Effects of CO were also observed with leukotrienes (LTs) and prostaglandins in that CO significantly decreased BAL fluid PGE(2), and LTB4 but exerted negligible effect on thromboxane B-2 or LTC4/D-4/E-4. Our data suggest a putative immunoregulatory role for CO in aeroallergen-induced inflammation in mice.	69	105	2001	8		Physiology; Respiratory System
Selected recombinant Aspergillus fumigatus allergens bind specifically to IgE in ABPA. Background Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease resulting from exposure to Aspergillus fumigatus allergens. Patients with ABPA show elevated Aspergillus-specific serum IgE, a major criterion used in the diagnosis of the disease. Crude culture filtrate and mycelial antigens have been used widely to demonstrate IgE antibody to Aspergillus in the sera of patients. While these antigens have been useful in the diagnosis of ABPA, occasionally they present inconsistency in their reactivity and lack of specificity. Although in recent years, a number of purified A. fumigatus allergens have been produced by molecular cloning, no attempt was made to evaluate them systematically. Objective To evaluate the recombinant proteins from A. fumigatus for their IgE antibody binding, we studied sera from ABPA patients and controls by antigen specific enzyme linked immunosorbent assay (ELISA). Methods Recombinant Aspergillus allergens Asp f 1, f 2, f 3, f 4, and f 6 were studied for their specific binding to IgE in the sera of ABPA patients, A. fumigatus skin prick test positive asthmatics, and normal controls from the USA and Switzerland. The sera were blinded and studied by ELISA in two different laboratories. Results All the recombinant allergens showed IgE antibody binding with sera from patients with ABPA, whereas only fewer asthmatics and normal sera showed significant binding. The three selected recombinant allergens together reacted with all the ABPA patients studied. Conclusions The results demonstrate that Asp f 2, f 4, and f 6 can be used in the serodiagnosis of ABPA, while IgE antibody binding to Asp f 1 and f 3 was not specific.. allergic asthma| allergic bronchopulmonary aspergillosis| elisa| recombinant aspergillus allergens| specific ige|skin-test reactivity| bronchopulmonary aspergillosis| major allergen| cystic-fibrosis| expression| cloning| system| i/a| purification| diagnosis.	JUL-2000	allergic asthma| allergic bronchopulmonary aspergillosis| elisa| recombinant aspergillus allergens| specific ige|skin-test reactivity| bronchopulmonary aspergillosis| major allergen| cystic-fibrosis| expression| cloning| system| i/a| purification| diagnosis	Kurup, VP; Banerjee, B; Hemmann, S; Greenberger, PA; Blaser, K; Crameri, R	Selected recombinant Aspergillus fumigatus allergens bind specifically to IgE in ABPA		CLINICAL AND EXPERIMENTAL ALLERGY	allergic asthma; allergic bronchopulmonary aspergillosis; ELISA; recombinant Aspergillus allergens; specific IgE	SKIN-TEST REACTIVITY; BRONCHOPULMONARY ASPERGILLOSIS; MAJOR ALLERGEN; CYSTIC-FIBROSIS; EXPRESSION; CLONING; SYSTEM; I/A; PURIFICATION; DIAGNOSIS	Background Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease resulting from exposure to Aspergillus fumigatus allergens. Patients with ABPA show elevated Aspergillus-specific serum IgE, a major criterion used in the diagnosis of the disease. Crude culture filtrate and mycelial antigens have been used widely to demonstrate IgE antibody to Aspergillus in the sera of patients. While these antigens have been useful in the diagnosis of ABPA, occasionally they present inconsistency in their reactivity and lack of specificity. Although in recent years, a number of purified A. fumigatus allergens have been produced by molecular cloning, no attempt was made to evaluate them systematically. Objective To evaluate the recombinant proteins from A. fumigatus for their IgE antibody binding, we studied sera from ABPA patients and controls by antigen specific enzyme linked immunosorbent assay (ELISA). Methods Recombinant Aspergillus allergens Asp f 1, f 2, f 3, f 4, and f 6 were studied for their specific binding to IgE in the sera of ABPA patients, A. fumigatus skin prick test positive asthmatics, and normal controls from the USA and Switzerland. The sera were blinded and studied by ELISA in two different laboratories. Results All the recombinant allergens showed IgE antibody binding with sera from patients with ABPA, whereas only fewer asthmatics and normal sera showed significant binding. The three selected recombinant allergens together reacted with all the ABPA patients studied. Conclusions The results demonstrate that Asp f 2, f 4, and f 6 can be used in the serodiagnosis of ABPA, while IgE antibody binding to Asp f 1 and f 3 was not specific.	25	105	2000	6		Allergy; Immunology
Nano spray drying: A novel method for preparing protein nanoparticles for protein therapy. There has been an increasing interest in the development of protein nanotherapeutics for diseases such as cancer, diabetes and asthma. Spray drying with prior micro mixing is commonly used to obtain these powders. However, the separation and collection of protein nanoparticles with conventional spray dryer setups has been known to be extremely challenging due to its typical low collection efficiency for fine particles less than 2 mu m. To date, there has been no feasible approach to produce these protein nanoparticles in a single step and with high yield (>70%). In this study, we explored the feasibility of the novel Nano Spray Dryer B-90 (equipped with a vibrating mesh spray technology and an electrostatic particle collector) for the production of bovine serum albumin (BSA) nanoparticles. A statistical experimental design method (Taguchi method based on three levels, five variables L-18 orthogonal array robust design) was implemented to study the effect of and optimize the experimental conditions of: (1) spray mesh size, (2) BSA solution concentration, (3) surfactant concentration, (4) drying air flow rate and (5) inlet temperature on: (1) size and (2) morphology (axial ratio). Particle size and morphology were predominantly influenced by the spray mesh size and surfactant concentration, respectively. The drying air flow rate and inlet temperature had minimal impact. Optimized production of smooth spherical nanoparticles (median size: 460 +/- 10 nm, axial ratio: 1.03 +/- 0.00, span 1.03 +/- 0.03, yield: 72 +/- 4%) was achieved using the 4 mu m spray mesh at BSA concentration of 0.1% (w/v), surfactant concentration of 0.05% (w/v), drying flow rate of 150 L/min and inlet temperature of 120 degrees C. The Nano Spray Dryer B-90 thus offers a new, simple and alternative approach for the production of protein nanoparticles suited for a variety of drug delivery applications. (C) 2010 Elsevier B.V. All rights reserved.. nano spray dryer| protein therapy| nanoparticles| bovine serum albumin| spray drying|formulation approach| aerosol performance| drug-delivery| powders| particles| stability| taguchi| crystallization| microparticles| optimization.	JAN 17-2011	nano spray dryer| protein therapy| nanoparticles| bovine serum albumin| spray drying|formulation approach| aerosol performance| drug-delivery| powders| particles| stability| taguchi| crystallization| microparticles| optimization	Lee, SH; Heng, D; Ng, WK; Chan, HK; Tan, RBH	Nano spray drying: A novel method for preparing protein nanoparticles for protein therapy		INTERNATIONAL JOURNAL OF PHARMACEUTICS	Nano spray dryer; Protein therapy; Nanoparticles; Bovine serum albumin; Spray drying	FORMULATION APPROACH; AEROSOL PERFORMANCE; DRUG-DELIVERY; POWDERS; PARTICLES; STABILITY; TAGUCHI; CRYSTALLIZATION; MICROPARTICLES; OPTIMIZATION	There has been an increasing interest in the development of protein nanotherapeutics for diseases such as cancer, diabetes and asthma. Spray drying with prior micro mixing is commonly used to obtain these powders. However, the separation and collection of protein nanoparticles with conventional spray dryer setups has been known to be extremely challenging due to its typical low collection efficiency for fine particles less than 2 mu m. To date, there has been no feasible approach to produce these protein nanoparticles in a single step and with high yield (>70%). In this study, we explored the feasibility of the novel Nano Spray Dryer B-90 (equipped with a vibrating mesh spray technology and an electrostatic particle collector) for the production of bovine serum albumin (BSA) nanoparticles. A statistical experimental design method (Taguchi method based on three levels, five variables L-18 orthogonal array robust design) was implemented to study the effect of and optimize the experimental conditions of: (1) spray mesh size, (2) BSA solution concentration, (3) surfactant concentration, (4) drying air flow rate and (5) inlet temperature on: (1) size and (2) morphology (axial ratio). Particle size and morphology were predominantly influenced by the spray mesh size and surfactant concentration, respectively. The drying air flow rate and inlet temperature had minimal impact. Optimized production of smooth spherical nanoparticles (median size: 460 +/- 10 nm, axial ratio: 1.03 +/- 0.00, span 1.03 +/- 0.03, yield: 72 +/- 4%) was achieved using the 4 mu m spray mesh at BSA concentration of 0.1% (w/v), surfactant concentration of 0.05% (w/v), drying flow rate of 150 L/min and inlet temperature of 120 degrees C. The Nano Spray Dryer B-90 thus offers a new, simple and alternative approach for the production of protein nanoparticles suited for a variety of drug delivery applications. (C) 2010 Elsevier B.V. All rights reserved.	44	104	2011	9	10.1016/j.ijpharm.2010.10.012	Pharmacology & Pharmacy
Safety and tolerability of omalizumab. Omalizumab (Xolair((R))) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. To review clinical study data to assess the safety profile of omalizumab. We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia. Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57 300 patients (June 2003-December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab. Data indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile.. anti-ige| omalizumab| safety| tolerability|severe allergic-asthma| anti-ige antibody| antiimmunoglobulin-e therapy| churg-strauss-syndrome| severe persistent asthma| long-term control| quality-of-life| monoclonal-antibody| cancer incidence| crohns-disease.	JUN-2009	anti-ige| omalizumab| safety| tolerability|severe allergic-asthma| anti-ige antibody| antiimmunoglobulin-e therapy| churg-strauss-syndrome| severe persistent asthma| long-term control| quality-of-life| monoclonal-antibody| cancer incidence| crohns-disease	Corren, J; Casale, TB; Lanier, B; Buhl, R; Holgate, S; Jimenez, P	Safety and tolerability of omalizumab		CLINICAL AND EXPERIMENTAL ALLERGY	anti-IgE; omalizumab; safety; tolerability	SEVERE ALLERGIC-ASTHMA; ANTI-IGE ANTIBODY; ANTIIMMUNOGLOBULIN-E THERAPY; CHURG-STRAUSS-SYNDROME; SEVERE PERSISTENT ASTHMA; LONG-TERM CONTROL; QUALITY-OF-LIFE; MONOCLONAL-ANTIBODY; CANCER INCIDENCE; CROHNS-DISEASE	Omalizumab (Xolair((R))) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. To review clinical study data to assess the safety profile of omalizumab. We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia. Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57 300 patients (June 2003-December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab. Data indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile.	51	104	2009	10	10.1111/j.1365-2222.2009.03214.x	Allergy; Immunology
Serial viral infections in infants with recurrent respiratory illnesses. To better understand the viral aetiology of recurrent and prolonged illnesses, nasal secretions were prospectively collected from 285 infants at increased risk of developing asthma. Of these, 27 infants had recurrent (at least five) moderate-to-severe respiratory illnesses (MSIs). The viral aetiology of the 150 MSIs and 86 scheduled visits was analysed by molecular diagnostics. The demographic and clinical data were compared with infants who had 0-4 MSIs. Frequently ill infants had higher exposure to other children and more wheezing illnesses than less symptomatic children. Viruses were detected in 136 (91 %) out of 150 MSIs, 14 (67%) out of 21 mild illnesses and 29 (45%) out of 65 asymptomatic visits. Human rhinovirus was the most common aetiological agent (61, 43 and 35% in MSIs, mild illnesses and asymptomatic visits, respectively). Mixed viral infections were generally associated with more severe illnesses (27, 0 and 5%, respectively). Among the 27 frequently ill infants, only eight (5.3%) out of 150 MSIs were prolonged (>= 2 weeks duration). Considering all samples, detection of the same virus strain >= 2 weeks apart was unusual (5.3% of all 244 positive findings). Human rhinovirus infections occur early, pervasively and repetitively in these high-risk infants. Infants with prolonged or recurrent respiratory illnesses most often have a series of infections rather than persistent infection with one virus strain.. infant| respiratory virus| rhinovirus| virus persistence| virus strain| wheezing|rhinovirus infection| acute bronchiolitis| childhood asthma| children| life| association| persistence| 1st-year| symptoms| viruses.	AUG-2008	infant| respiratory virus| rhinovirus| virus persistence| virus strain| wheezing|rhinovirus infection| acute bronchiolitis| childhood asthma| children| life| association| persistence| 1st-year| symptoms| viruses	Jartti, T; Lee, WM; Pappas, T; Evans, M; Lemanske, RF; Gern, JE	Serial viral infections in infants with recurrent respiratory illnesses		EUROPEAN RESPIRATORY JOURNAL	infant; respiratory virus; rhinovirus; virus persistence; virus strain; wheezing	RHINOVIRUS INFECTION; ACUTE BRONCHIOLITIS; CHILDHOOD ASTHMA; CHILDREN; LIFE; ASSOCIATION; PERSISTENCE; 1ST-YEAR; SYMPTOMS; VIRUSES	To better understand the viral aetiology of recurrent and prolonged illnesses, nasal secretions were prospectively collected from 285 infants at increased risk of developing asthma. Of these, 27 infants had recurrent (at least five) moderate-to-severe respiratory illnesses (MSIs). The viral aetiology of the 150 MSIs and 86 scheduled visits was analysed by molecular diagnostics. The demographic and clinical data were compared with infants who had 0-4 MSIs. Frequently ill infants had higher exposure to other children and more wheezing illnesses than less symptomatic children. Viruses were detected in 136 (91 %) out of 150 MSIs, 14 (67%) out of 21 mild illnesses and 29 (45%) out of 65 asymptomatic visits. Human rhinovirus was the most common aetiological agent (61, 43 and 35% in MSIs, mild illnesses and asymptomatic visits, respectively). Mixed viral infections were generally associated with more severe illnesses (27, 0 and 5%, respectively). Among the 27 frequently ill infants, only eight (5.3%) out of 150 MSIs were prolonged (>= 2 weeks duration). Considering all samples, detection of the same virus strain >= 2 weeks apart was unusual (5.3% of all 244 positive findings). Human rhinovirus infections occur early, pervasively and repetitively in these high-risk infants. Infants with prolonged or recurrent respiratory illnesses most often have a series of infections rather than persistent infection with one virus strain.	30	104	2008	7	10.1183/09031936.00161907	Respiratory System
Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe. Background Dietary interventions as a means for atopy prevention attract great interest. Some studies in rural environments claimed an inverse association between consumption of farm-produced dairy products and the prevalence of allergic diseases, but current evidence is controversial. Objective To investigate whether consumption of farm-produced products is associated with a lower prevalence of asthma and allergy when compared with shop-purchased products. Methods Cross sectional multi-centre study (PARSIFAL) including 14 893 children aged 5-13 years from five European countries (2823 from farm families and 4606 attending Steiner Schools as well as 5440 farm reference and 2024 Steiner reference children). A detailed questionnaire including a dietary component was completed and allergen-specific IgE was measured in serum. Results Farm milk consumption ever in life showed a statistically significant inverse association with asthma: covariate adjusted odds ratio (aOR) 0.74 [95% confidence interval (CI) 0.61-0.88], rhinoconjunctivitis: aOR 0.56 (0.43-0.73) and sensitization to pollen and the food mix fx5 (cut-off level of >= 3.5 kU/L): aOR 0.67 (0.47-0.96) and aOR 0.42 (0.19-0.92), respectively, and sensitization to horse dander: aOR 0.50 (95% CI 0.28-0.87). The associations were observed in all four subpopulations and independent of farm-related co-exposures. Other farm-produced products were not independently related to any allergy-related health outcome. Conclusion Our results indicate that consumption of farm milk may offer protection against asthma and allergy. A deepened understanding of the relevant protective components of farm milk and a better insight into the biological mechanisms underlying this association are warranted as a basis for the development of a safe product for prevention.. allergy| anthroposophy| asthma| children| diet| farming| gastrointestinal microflora| self-production| sensitization|anthroposophic life-style| hay-fever| fungal microbiota| low-prevalence| birth cohort| children| atopy| childhood| diseases| risk.	MAY-2007	allergy| anthroposophy| asthma| children| diet| farming| gastrointestinal microflora| self-production| sensitization|anthroposophic life-style| hay-fever| fungal microbiota| low-prevalence| birth cohort| children| atopy| childhood| diseases| risk	Waser, M; Michels, KB; Bieli, C; Floistrup, H; Pershagen, G; von Mutius, E; Ege, M; Riedler, J; Schram-Bijkerk, D; Brunekreef, B; van Hage, M; Lauener, R; Braun-Fahrlander, C	Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; anthroposophy; asthma; children; diet; farming; gastrointestinal microflora; self-production; sensitization	ANTHROPOSOPHIC LIFE-STYLE; HAY-FEVER; FUNGAL MICROBIOTA; LOW-PREVALENCE; BIRTH COHORT; CHILDREN; ATOPY; CHILDHOOD; DISEASES; RISK	Background Dietary interventions as a means for atopy prevention attract great interest. Some studies in rural environments claimed an inverse association between consumption of farm-produced dairy products and the prevalence of allergic diseases, but current evidence is controversial. Objective To investigate whether consumption of farm-produced products is associated with a lower prevalence of asthma and allergy when compared with shop-purchased products. Methods Cross sectional multi-centre study (PARSIFAL) including 14 893 children aged 5-13 years from five European countries (2823 from farm families and 4606 attending Steiner Schools as well as 5440 farm reference and 2024 Steiner reference children). A detailed questionnaire including a dietary component was completed and allergen-specific IgE was measured in serum. Results Farm milk consumption ever in life showed a statistically significant inverse association with asthma: covariate adjusted odds ratio (aOR) 0.74 [95% confidence interval (CI) 0.61-0.88], rhinoconjunctivitis: aOR 0.56 (0.43-0.73) and sensitization to pollen and the food mix fx5 (cut-off level of >= 3.5 kU/L): aOR 0.67 (0.47-0.96) and aOR 0.42 (0.19-0.92), respectively, and sensitization to horse dander: aOR 0.50 (95% CI 0.28-0.87). The associations were observed in all four subpopulations and independent of farm-related co-exposures. Other farm-produced products were not independently related to any allergy-related health outcome. Conclusion Our results indicate that consumption of farm milk may offer protection against asthma and allergy. A deepened understanding of the relevant protective components of farm milk and a better insight into the biological mechanisms underlying this association are warranted as a basis for the development of a safe product for prevention.	36	104	2007	10	10.1111/j.1365-2222.2006.02640.x	Allergy; Immunology
Life stress and diminished expression of genes encoding glucocorticoid receptor and beta(2)-adrenergic receptor in children with asthma. Despite evidence that stressful experience can exacerbate the symptoms of asthma, little is known about the biological mechanisms through which this occurs. This study examined whether life stress reduces expression of the genes coding for the glucocorticoid receptor and the beta(2)-adrenergic receptor. A total of 77 children were enrolled in the study (59% male; mean age, 13.5 years). Thirty-nine of them were physician-diagnosed with asthma, and 38 were healthy. After an in-depth interview regarding stressful experiences, leukocytes were collected through antecubital venipuncture, and real-time RT-PCR was used to quantify mRNA. Chronic stress was associated with reduced expression of mRNA for the beta(2)-adrenergic receptor among children with asthma. In the sample of healthy children, however, the direction of this effect was reversed. The occurrence of a major life event in the 6 months before the study was not sufficient to influence patterns of gene expression. When such events occurred in the context of a chronic stressor, however, their association with patterns of gene expression was accentuated. Children with asthma who simultaneously experienced acute and chronic stress exhibited a 5.5-fold reduction in glucocorticoid receptor mRNA and a 9.5-fold reduction in beta(2)-adrenergic receptor mRNA relative to children with asthma without comparable stressor exposure. These findings suggest that stressful experience diminishes expression of the glucocorticoid and beta(2)-adrenergic receptor genes in children with asthma. To the extent that it diminishes sensitivity to the antiinflammatory properties of glucocorticoids or the bronchodilatory properties of beta-agonists, this process could explain the increased asthma morbidity associated with stress.. cytokine profiles| childhood asthma| messenger-rna| birth-cohort| generation| inflammation| depression| resistance| challenge| exposure.	APR 4-2006	cytokine profiles| childhood asthma| messenger-rna| birth-cohort| generation| inflammation| depression| resistance| challenge| exposure	Miller, GE; Chen, E	Life stress and diminished expression of genes encoding glucocorticoid receptor and beta(2)-adrenergic receptor in children with asthma		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA		CYTOKINE PROFILES; CHILDHOOD ASTHMA; MESSENGER-RNA; BIRTH-COHORT; GENERATION; INFLAMMATION; DEPRESSION; RESISTANCE; CHALLENGE; EXPOSURE	Despite evidence that stressful experience can exacerbate the symptoms of asthma, little is known about the biological mechanisms through which this occurs. This study examined whether life stress reduces expression of the genes coding for the glucocorticoid receptor and the beta(2)-adrenergic receptor. A total of 77 children were enrolled in the study (59% male; mean age, 13.5 years). Thirty-nine of them were physician-diagnosed with asthma, and 38 were healthy. After an in-depth interview regarding stressful experiences, leukocytes were collected through antecubital venipuncture, and real-time RT-PCR was used to quantify mRNA. Chronic stress was associated with reduced expression of mRNA for the beta(2)-adrenergic receptor among children with asthma. In the sample of healthy children, however, the direction of this effect was reversed. The occurrence of a major life event in the 6 months before the study was not sufficient to influence patterns of gene expression. When such events occurred in the context of a chronic stressor, however, their association with patterns of gene expression was accentuated. Children with asthma who simultaneously experienced acute and chronic stress exhibited a 5.5-fold reduction in glucocorticoid receptor mRNA and a 9.5-fold reduction in beta(2)-adrenergic receptor mRNA relative to children with asthma without comparable stressor exposure. These findings suggest that stressful experience diminishes expression of the glucocorticoid and beta(2)-adrenergic receptor genes in children with asthma. To the extent that it diminishes sensitivity to the antiinflammatory properties of glucocorticoids or the bronchodilatory properties of beta-agonists, this process could explain the increased asthma morbidity associated with stress.	34	104	2006	6	10.1073/pnas.0506312103	Science & Technology - Other Topics
Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome?. The term 'baboon syndrome' (BS) was introduced 20 years ago to classify patients in whom a specific skin eruption resembling the red gluteal area of baboons occurred after systemic exposure to contact allergens. Thereafter, similar eruptions have been reported after systemic exposure to beta-lactam antibiotics and other drugs. In addition to the presentation of 2 of our own cases, we have reviewed and characterized the main clinical and histological aspects of published reports of drug-related baboon syndrome (DRBS) and compared the primary clinical signs from such cases to those found in other distinct drug eruptions. Of approximately 100 published baboon syndrome cases, 50 were identified as drug-induced. Of these, 8 were representatives of systemically induced contact dermatitis (SCD), and 42 were examples of drug eruptions elicited by systemic administration of either oral or intravenous drugs. The main clinical findings included a sharply defined symmetrical erythema of the gluteal area and in the flexural or intertriginous folds without any systemic symptoms and signs. 14 of 42 cases were elicited by amoxicillin, 30 of the 42 patients were male, and latency periods were between a few hours and a few days after exposure. DRBS is a rare, prognostically benign and often underdiagnosed drug eruption with distinct clinical features. The term baboon syndrome, however, does not reflect the complete range of symptoms and signs and is ethically and culturally problematic. Moreover, baboon syndrome is historically often equated with a mercury-induced exanthem in patients with previous contact sensitization. Symmetrical drug-related intertriginous and flexural exanthema, or SDRIFE, specifically refers to the distinctive clinical pattern of this drug eruption, and the following diagnostic criteria are proposed: 1) exposure to a systemically administered drug either at the first or repeated dose (excluding contact allergens); 2) sharply demarcated erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area; 3) involvement of at least one other intertriginous/flexural localization; 4) symmetry of affected areas; and 5) absence of systemic symptoms and signs.. allergic contact dermatitis syndrome| baboon syndrome| systemic contact dermatitis|eruption| pseudoephedrine| exanthem| hypersensitivity| ethylenediamine| aminophylline| manifestation| amoxicillin| cinchocaine| mercury.	NOV-2004	allergic contact dermatitis syndrome| baboon syndrome| systemic contact dermatitis|eruption| pseudoephedrine| exanthem| hypersensitivity| ethylenediamine| aminophylline| manifestation| amoxicillin| cinchocaine| mercury	Hausermann, P; Harr, T; Bircher, AJ	Baboon syndrome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis syndrome?		CONTACT DERMATITIS	allergic contact dermatitis syndrome; baboon syndrome; systemic contact dermatitis	ERUPTION; PSEUDOEPHEDRINE; EXANTHEM; HYPERSENSITIVITY; ETHYLENEDIAMINE; AMINOPHYLLINE; MANIFESTATION; AMOXICILLIN; CINCHOCAINE; MERCURY	The term 'baboon syndrome' (BS) was introduced 20 years ago to classify patients in whom a specific skin eruption resembling the red gluteal area of baboons occurred after systemic exposure to contact allergens. Thereafter, similar eruptions have been reported after systemic exposure to beta-lactam antibiotics and other drugs. In addition to the presentation of 2 of our own cases, we have reviewed and characterized the main clinical and histological aspects of published reports of drug-related baboon syndrome (DRBS) and compared the primary clinical signs from such cases to those found in other distinct drug eruptions. Of approximately 100 published baboon syndrome cases, 50 were identified as drug-induced. Of these, 8 were representatives of systemically induced contact dermatitis (SCD), and 42 were examples of drug eruptions elicited by systemic administration of either oral or intravenous drugs. The main clinical findings included a sharply defined symmetrical erythema of the gluteal area and in the flexural or intertriginous folds without any systemic symptoms and signs. 14 of 42 cases were elicited by amoxicillin, 30 of the 42 patients were male, and latency periods were between a few hours and a few days after exposure. DRBS is a rare, prognostically benign and often underdiagnosed drug eruption with distinct clinical features. The term baboon syndrome, however, does not reflect the complete range of symptoms and signs and is ethically and culturally problematic. Moreover, baboon syndrome is historically often equated with a mercury-induced exanthem in patients with previous contact sensitization. Symmetrical drug-related intertriginous and flexural exanthema, or SDRIFE, specifically refers to the distinctive clinical pattern of this drug eruption, and the following diagnostic criteria are proposed: 1) exposure to a systemically administered drug either at the first or repeated dose (excluding contact allergens); 2) sharply demarcated erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area; 3) involvement of at least one other intertriginous/flexural localization; 4) symmetry of affected areas; and 5) absence of systemic symptoms and signs.	47	104	2004	14	10.1111/j.0105-1873.2004.00445.x	Allergy; Dermatology
A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children. Background: Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases. Objective: The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children. Methods: The TLR4 (Asp299Gly) and CD14/-159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-gamma responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden). Results: Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis. Conclusion: A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators.. asthma| tlr4| lipopolysaccharide| il-12| il-10|toll-like receptor-4| t-cell| endotoxin exposure| interferon-gamma| allergic disease| ige production| house-dust| cd14 gene| atopy| challenge.	SEP-2004	asthma| tlr4| lipopolysaccharide| il-12| il-10|toll-like receptor-4| t-cell| endotoxin exposure| interferon-gamma| allergic disease| ige production| house-dust| cd14 gene| atopy| challenge	Bottcher, MF; Hmani-Aifa, M; Lindstrom, A; Jenmalm, MC; Mai, XM; Nilsson, L; Zdolsek, HA; Bjorksten, B; Soderkvist, P; Vaarala, O	A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; TLR4; lipopolysaccharide; IL-12; IL-10	TOLL-LIKE RECEPTOR-4; T-CELL; ENDOTOXIN EXPOSURE; INTERFERON-GAMMA; ALLERGIC DISEASE; IGE PRODUCTION; HOUSE-DUST; CD14 GENE; ATOPY; CHALLENGE	Background: Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases. Objective: The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children. Methods: The TLR4 (Asp299Gly) and CD14/-159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-gamma responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden). Results: Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis. Conclusion: A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators.	32	104	2004	7	10.1016/j.jaci.2004.04.050	Allergy; Immunology
Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life. Objectives To determine whether early infectious diseases could explain the association between number of siblings and other markers of microbial exposure and the development of atopic dermatitis before the age of 18 months. Design Cohort study. Information on atopic dermatitis, infectious diseases occurring before 6 months of age, number of siblings, early day care, pet keeping, farm residence, and background factors was collected in telephone interviews. Setting Danish national birth cohort. Participants 24341 mother-child pairs. Main outcome measures Incidence rate ratios of atopic dermatitis. Results 13070 children (54%) had at least one clinically apparent infectious disease before 6 months of age. At age 18 months, 2638 (10.8%) of the children had had atopic dermatitis. The risk of atopic dermatitis increased with each infectious disease before 6 months of age (incidence rate ratio 1.08,95% confidence interval 1.04 to 1.13). The risk of atopic dermatitis decreased with each additional exposure to three or more siblings, day care, pet ownership, and farm residence (0.86, 0.81 to 0.93). Conclusions Early infections do not seem to protect against allergic diseases. The protective effect of number of siblings, day care, pet ownership, and farm residence remained after adjustment for clinically apparent infectious diseases, suggesting that the effect is established independently early in life.. family-size| hay-fever| respiratory-infections| birth cohort| children| asthma| prevalence| allergy| determinants| antibodies.	MAY 22-2004	family-size| hay-fever| respiratory-infections| birth cohort| children| asthma| prevalence| allergy| determinants| antibodies	Benn, CS; Melbye, M; Wohlfahrt, J; Bjorksten, B; Aaby, P	Cohort study of sibling effect, infectious diseases, and risk of atopic dermatitis during first 18 months of life		BRITISH MEDICAL JOURNAL		FAMILY-SIZE; HAY-FEVER; RESPIRATORY-INFECTIONS; BIRTH COHORT; CHILDREN; ASTHMA; PREVALENCE; ALLERGY; DETERMINANTS; ANTIBODIES	Objectives To determine whether early infectious diseases could explain the association between number of siblings and other markers of microbial exposure and the development of atopic dermatitis before the age of 18 months. Design Cohort study. Information on atopic dermatitis, infectious diseases occurring before 6 months of age, number of siblings, early day care, pet keeping, farm residence, and background factors was collected in telephone interviews. Setting Danish national birth cohort. Participants 24341 mother-child pairs. Main outcome measures Incidence rate ratios of atopic dermatitis. Results 13070 children (54%) had at least one clinically apparent infectious disease before 6 months of age. At age 18 months, 2638 (10.8%) of the children had had atopic dermatitis. The risk of atopic dermatitis increased with each infectious disease before 6 months of age (incidence rate ratio 1.08,95% confidence interval 1.04 to 1.13). The risk of atopic dermatitis decreased with each additional exposure to three or more siblings, day care, pet ownership, and farm residence (0.86, 0.81 to 0.93). Conclusions Early infections do not seem to protect against allergic diseases. The protective effect of number of siblings, day care, pet ownership, and farm residence remained after adjustment for clinically apparent infectious diseases, suggesting that the effect is established independently early in life.	23	104	2004	6	10.1136/bmj.38069.512245.FE	General & Internal Medicine
Early-life environmental risk factors for asthma: Findings from the children's health study. Early-life experiences and environmental exposures have. been associated with childhood asthma. To investigate further whether the timing of such experiences and exposures is associated with the occurrence of asthma by 5 years of age, we conducted a prevalence case-control study nested within the Children's Health Study, a population-based study of > 4,000 school-aged children in 12 southern California communities. Cases were defined as physician-diagnosed asthma by age 5, and controls were asthma-free at study entry, frequency- matched on age, sex, and community of residence and countermatched on in utero exposure to maternal smoking. Telephone interviews were conducted with mothers to collect additional exposure and asthma histories. Conditional logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Asthma diagnosis before 5 years of age was associated with exposures in the first year of life to wood or oil smoke, soot, or exhaust (OR = 1.74; 95% CI, 1.02-2.96), cockroaches (OR = 2.03; 95% CI, 1.03-4.02), herbicides (OR = 4.58; 95% CI, 1.36-15.43), pesticides (OR = 2.39; 95% CI, 1.17-4.89), and farm crops, farm dust, or farm animals (OR = 1.88; 95% CI, 1.07-3.28). The ORs for herbicide, pesticide, farm animal, and crops were largest among children with early-onset persistent asthma. The risk of asthma decreased with an increasing number of siblings (P-trend 0.01). Day care attendance within the first 4 months of life was positively associated with early-onset transient wheezing (OR = 2.42; 95% CI, 1.28-4.59). In conclusion, environmental exposures during the first year of life are associated with childhood asthma risk.. asthma| breast-feeding| cockroach| day care| farm environment| herbicide| pesticide| sibship size| wood smoke|southern california communities| inner-city children| day-care attendance| pulmonary-function| childhood asthma| 1st year| cockroach allergen| differing levels| early exposure| air-pollution.	MAY-2004	asthma| breast-feeding| cockroach| day care| farm environment| herbicide| pesticide| sibship size| wood smoke|southern california communities| inner-city children| day-care attendance| pulmonary-function| childhood asthma| 1st year| cockroach allergen| differing levels| early exposure| air-pollution	Salam, MT; Li, YF; Langholz, B; Gilliland, FD	Early-life environmental risk factors for asthma: Findings from the children's health study		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; breast-feeding; cockroach; day care; farm environment; herbicide; pesticide; sibship size; wood smoke	SOUTHERN CALIFORNIA COMMUNITIES; INNER-CITY CHILDREN; DAY-CARE ATTENDANCE; PULMONARY-FUNCTION; CHILDHOOD ASTHMA; 1ST YEAR; COCKROACH ALLERGEN; DIFFERING LEVELS; EARLY EXPOSURE; AIR-POLLUTION	Early-life experiences and environmental exposures have. been associated with childhood asthma. To investigate further whether the timing of such experiences and exposures is associated with the occurrence of asthma by 5 years of age, we conducted a prevalence case-control study nested within the Children's Health Study, a population-based study of > 4,000 school-aged children in 12 southern California communities. Cases were defined as physician-diagnosed asthma by age 5, and controls were asthma-free at study entry, frequency- matched on age, sex, and community of residence and countermatched on in utero exposure to maternal smoking. Telephone interviews were conducted with mothers to collect additional exposure and asthma histories. Conditional logistic regression models were fitted to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Asthma diagnosis before 5 years of age was associated with exposures in the first year of life to wood or oil smoke, soot, or exhaust (OR = 1.74; 95% CI, 1.02-2.96), cockroaches (OR = 2.03; 95% CI, 1.03-4.02), herbicides (OR = 4.58; 95% CI, 1.36-15.43), pesticides (OR = 2.39; 95% CI, 1.17-4.89), and farm crops, farm dust, or farm animals (OR = 1.88; 95% CI, 1.07-3.28). The ORs for herbicide, pesticide, farm animal, and crops were largest among children with early-onset persistent asthma. The risk of asthma decreased with an increasing number of siblings (P-trend 0.01). Day care attendance within the first 4 months of life was positively associated with early-onset transient wheezing (OR = 2.42; 95% CI, 1.28-4.59). In conclusion, environmental exposures during the first year of life are associated with childhood asthma risk.	45	104	2004	6	10.1289/ehp.6662	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
In vitro allergy diagnosis: should we follow the flow?. During the last 5 years, an increasing number of studies have demonstrated that flow cytometric quantification of in vitro basophil activation can be a quite performant and reliable tool to measure IgE-dependent allergen-specific responses in allergic patients. So far, most assays have used CD63 as a basophil activation marker and native allergen extracts for stimulation. However, other basophil markers and recombinant allergens have recently been introduced. The technique has been applied for the diagnosis of allergy to pollen, house dust mite, food, natural rubber latex, hymenoptera venom and drugs. In addition, the technique has proven to be useful in non-IgE-mediated reactions such as hypersensitivity to drugs as well as detection of auto-antibodies in chronic urticaria. This review will focus on some specific issues: (1) principles of flow cytometric analysis of in vitro-activated basophils, (2) general technical aspects of the technique (including passive sensitization), (3) clinical applications and (4) recommendations for further development and evaluation of the technique.. basophil histamine-release| grass-pollen allergens| rubber latex allergy| human mast-cells| hymenoptera-venom| recombinant allergens| cd63 expression| activation test| ige antibodies| cdna cloning.	MAR-2004	basophil histamine-release| grass-pollen allergens| rubber latex allergy| human mast-cells| hymenoptera-venom| recombinant allergens| cd63 expression| activation test| ige antibodies| cdna cloning	Ebo, DG; Hagendorens, MM; Bridts, CH; Schuerwegh, AJ; De Clerck, LS; Stevens, WJ	In vitro allergy diagnosis: should we follow the flow?		CLINICAL AND EXPERIMENTAL ALLERGY		BASOPHIL HISTAMINE-RELEASE; GRASS-POLLEN ALLERGENS; RUBBER LATEX ALLERGY; HUMAN MAST-CELLS; HYMENOPTERA-VENOM; RECOMBINANT ALLERGENS; CD63 EXPRESSION; ACTIVATION TEST; IGE ANTIBODIES; CDNA CLONING	During the last 5 years, an increasing number of studies have demonstrated that flow cytometric quantification of in vitro basophil activation can be a quite performant and reliable tool to measure IgE-dependent allergen-specific responses in allergic patients. So far, most assays have used CD63 as a basophil activation marker and native allergen extracts for stimulation. However, other basophil markers and recombinant allergens have recently been introduced. The technique has been applied for the diagnosis of allergy to pollen, house dust mite, food, natural rubber latex, hymenoptera venom and drugs. In addition, the technique has proven to be useful in non-IgE-mediated reactions such as hypersensitivity to drugs as well as detection of auto-antibodies in chronic urticaria. This review will focus on some specific issues: (1) principles of flow cytometric analysis of in vitro-activated basophils, (2) general technical aspects of the technique (including passive sensitization), (3) clinical applications and (4) recommendations for further development and evaluation of the technique.	98	104	2004	8	10.1111/j.1365-2222.2004.01891.x	Allergy; Immunology
Having lived on a farm and protection against allergic diseases in Australia. Background Farmers' children in northern Europe have a lower prevalence of atopy, hay fever and asthma than other children. Farms in Australia differ in scale and operation from those in Europe and the prevalence of allergic diseases in children is higher. Objective To investigate whether having lived on a farm as a child in Australia is associated with a lower risk of allergic diseases. Methods Cross-sectional study of children (n = 1500) aged 7-12 years from two rural towns: Wagga Wagga in a mixed farming region, and Moree in a crop farming region. Parents answered a questionnaire and children had a skin prick test for atopy. Results Twenty percent of children had lived on a farm for at least 1 year. The effect of having lived on a farm differed between the towns (P < 0.001). It was associated with a lower risk of atopy in Wagga (adjusted odds ratio (aOR) 0.47, 95% confidence interval (CI) 0.32-0.72) but not in Moree (aOR 0.97, 95% CI 0.62-1.53). Children from Wagga were more likely to have lived on a livestock farm than children from Moree (26.1% vs. 9.1%, 95% CI for the difference 8.9-25.4). Conclusion Having lived on a farm in Australia can confer protection against atopy in children. Further studies are needed to identify possible protective mechanisms associated with farm animals or to establish whether the protective effect is explained by other related exposures.. atopy| farming| children| allergic diseases|hay-fever| asthma| childhood| children| sensitization| exposure| prevalence| history.	APR-2001	atopy| farming| children| allergic diseases|hay-fever| asthma| childhood| children| sensitization| exposure| prevalence| history	Downs, SH; Marks, GB; Mitakakis, TZ; Leuppi, JD; Car, NG; Peat, JK	Having lived on a farm and protection against allergic diseases in Australia		CLINICAL AND EXPERIMENTAL ALLERGY	atopy; farming; children; allergic diseases	HAY-FEVER; ASTHMA; CHILDHOOD; CHILDREN; SENSITIZATION; EXPOSURE; PREVALENCE; HISTORY	Background Farmers' children in northern Europe have a lower prevalence of atopy, hay fever and asthma than other children. Farms in Australia differ in scale and operation from those in Europe and the prevalence of allergic diseases in children is higher. Objective To investigate whether having lived on a farm as a child in Australia is associated with a lower risk of allergic diseases. Methods Cross-sectional study of children (n = 1500) aged 7-12 years from two rural towns: Wagga Wagga in a mixed farming region, and Moree in a crop farming region. Parents answered a questionnaire and children had a skin prick test for atopy. Results Twenty percent of children had lived on a farm for at least 1 year. The effect of having lived on a farm differed between the towns (P < 0.001). It was associated with a lower risk of atopy in Wagga (adjusted odds ratio (aOR) 0.47, 95% confidence interval (CI) 0.32-0.72) but not in Moree (aOR 0.97, 95% CI 0.62-1.53). Children from Wagga were more likely to have lived on a livestock farm than children from Moree (26.1% vs. 9.1%, 95% CI for the difference 8.9-25.4). Conclusion Having lived on a farm in Australia can confer protection against atopy in children. Further studies are needed to identify possible protective mechanisms associated with farm animals or to establish whether the protective effect is explained by other related exposures.	30	104	2001	6	10.1046/j.1365-2222.2001.01070.x	Allergy; Immunology
Airway subepithelial fibrosis in a murine model of atopic asthma - Suppression by dexamethasone or anti-interleukin-5 antibody. Fibrosis in the reticular layer beneath the epithelial basement membrane Is a feature of airway remodeling in human asthma, We previously reported the presence of subepithelial fibrosis (SEF) in a disease model of atopic asthma in which mice were sensitized and intratracheally challenged with ovalbumin (OVA) (Blyth and colleagues, Am. J. Respir. Cell Mol. Biol, 1996;14:425-438), Here, we describe further studies to quantify the degree of SEF after its induction by repeated exposure of the airways to allergen. The amount of subepithelial reticulin in the airways of animals challenged three times with 80 mu g OVA was typically increased 1.4-fold. The increased amount of reticulin showed no reduction after a 50-d period after the third allergen challenge. A reduction in SEF was achieved by daily treatment with dexamethasone (DEX) for 8 d during the allergen challenge period, or by treatment with anti-interleukin-5 antibody (TRFK5) at the time of allergen challenge, Postchallenge treatment with DEX for 15 d resulted in significant resolution of previously established SEF, Severe nonallergic inflammation during repeated exposure of airways to lipopolysaccharide did not induce SEF. The results indicate that development of SEF is associated with eosinophil infiltration into airways, and may occur only when the inflammatory stimulus is allergic in nature.. bronchial-asthma| basement-membrane| cell hyperplasia| inflammation| expression| collagen| wall| hyperreactivity| responsiveness| methacholine.	AUG-2000	bronchial-asthma| basement-membrane| cell hyperplasia| inflammation| expression| collagen| wall| hyperreactivity| responsiveness| methacholine	Blyth, DI; Wharton, TF; Pedrick, MS; Savage, TJ; Sanjar, S	Airway subepithelial fibrosis in a murine model of atopic asthma - Suppression by dexamethasone or anti-interleukin-5 antibody		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		BRONCHIAL-ASTHMA; BASEMENT-MEMBRANE; CELL HYPERPLASIA; INFLAMMATION; EXPRESSION; COLLAGEN; WALL; HYPERREACTIVITY; RESPONSIVENESS; METHACHOLINE	Fibrosis in the reticular layer beneath the epithelial basement membrane Is a feature of airway remodeling in human asthma, We previously reported the presence of subepithelial fibrosis (SEF) in a disease model of atopic asthma in which mice were sensitized and intratracheally challenged with ovalbumin (OVA) (Blyth and colleagues, Am. J. Respir. Cell Mol. Biol, 1996;14:425-438), Here, we describe further studies to quantify the degree of SEF after its induction by repeated exposure of the airways to allergen. The amount of subepithelial reticulin in the airways of animals challenged three times with 80 mu g OVA was typically increased 1.4-fold. The increased amount of reticulin showed no reduction after a 50-d period after the third allergen challenge. A reduction in SEF was achieved by daily treatment with dexamethasone (DEX) for 8 d during the allergen challenge period, or by treatment with anti-interleukin-5 antibody (TRFK5) at the time of allergen challenge, Postchallenge treatment with DEX for 15 d resulted in significant resolution of previously established SEF, Severe nonallergic inflammation during repeated exposure of airways to lipopolysaccharide did not induce SEF. The results indicate that development of SEF is associated with eosinophil infiltration into airways, and may occur only when the inflammatory stimulus is allergic in nature.	42	104	2000	6		Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. Classic atopic dermatitis is complicated by asthma, allergic rhinitis, and food allergies, cumulatively referred to as atopic diseases. Recent discoveries of mutations in the filaggrin gene as predisposing factors for atopic diseases have refocused investigators' attention on epidermal barrier dysfunction as a causative mechanism. The skin's barrier function has three elements: the stratum corneum (air-liquid barrier), tight junctions (liquid-liquid barrier), and the Langerhans cell network (immunological barrier). Clarification of the molecular events underpinning epidermal barrier function and dysfunction should lead to a better understanding of the pathophysiological mechanisms of atopic diseases.. thymic stromal lymphopoietin| epithelial tight junctions| protease bleomycin hydrolase| down-regulates filaggrin| of-function mutations| stratum-corneum| langerhans cells| dendritic cells| netherton-syndrome| skin-barrier.	FEB-2012	thymic stromal lymphopoietin| epithelial tight junctions| protease bleomycin hydrolase| down-regulates filaggrin| of-function mutations| stratum-corneum| langerhans cells| dendritic cells| netherton-syndrome| skin-barrier	Kubo, A; Nagao, K; Amagai, M	Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases		JOURNAL OF CLINICAL INVESTIGATION		THYMIC STROMAL LYMPHOPOIETIN; EPITHELIAL TIGHT JUNCTIONS; PROTEASE BLEOMYCIN HYDROLASE; DOWN-REGULATES FILAGGRIN; OF-FUNCTION MUTATIONS; STRATUM-CORNEUM; LANGERHANS CELLS; DENDRITIC CELLS; NETHERTON-SYNDROME; SKIN-BARRIER	Classic atopic dermatitis is complicated by asthma, allergic rhinitis, and food allergies, cumulatively referred to as atopic diseases. Recent discoveries of mutations in the filaggrin gene as predisposing factors for atopic diseases have refocused investigators' attention on epidermal barrier dysfunction as a causative mechanism. The skin's barrier function has three elements: the stratum corneum (air-liquid barrier), tight junctions (liquid-liquid barrier), and the Langerhans cell network (immunological barrier). Clarification of the molecular events underpinning epidermal barrier function and dysfunction should lead to a better understanding of the pathophysiological mechanisms of atopic diseases.	126	103	2012	8	10.1172/JCI57416	Research & Experimental Medicine
"Epigenetics and Prenatal Influences on Asthma and Allergic Airways Disease. Uterine life is arguably the most critical time in developmental programming, when environmental exposures may have the greatest potential to influence evolving fetal structure and function. There has been substantial progress in understanding the epigenetic mechanisms through which environmental exposures can permanently alter the expression of fetal genes and contribute to the increasing propensity for many complex diseases. These concepts of ""developmental origins"" of disease are being applied across virtually all fields of medicine, and emerging epigenetic paradigms are the likely mechanism behind the environment-driven epidemic of asthma and allergic disease. Here, we examine the epigenetic regulation of immune development and the early immune profiles that contribute to allergic risk. In particular we review new evidence that key environmental exposures, such as microbial exposure, dietary changes, tobacco smoke, and pollutants, can induce epigenetic changes in gene expression and alter disease risk. Although most of these factors have already been clearly implicated in epidemiologic studies of asthma and allergic disease, new studies investigating the mechanisms of these effects may provide new avenues for using these pathways for disease prevention. CHEST 2011; 139(3):640-647. obstructive pulmonary-disease| tobacco-smoke exposure| regulatory t-cells| ifn-gamma promoter| maternal smoking| childhood asthma| subsequent development| developmental origins| postnatal-development| cytokine responses."	MAR-2011	obstructive pulmonary-disease| tobacco-smoke exposure| regulatory t-cells| ifn-gamma promoter| maternal smoking| childhood asthma| subsequent development| developmental origins| postnatal-development| cytokine responses	Martino, D; Prescott, S	Epigenetics and Prenatal Influences on Asthma and Allergic Airways Disease		CHEST		OBSTRUCTIVE PULMONARY-DISEASE; TOBACCO-SMOKE EXPOSURE; REGULATORY T-CELLS; IFN-GAMMA PROMOTER; MATERNAL SMOKING; CHILDHOOD ASTHMA; SUBSEQUENT DEVELOPMENT; DEVELOPMENTAL ORIGINS; POSTNATAL-DEVELOPMENT; CYTOKINE RESPONSES	"Uterine life is arguably the most critical time in developmental programming, when environmental exposures may have the greatest potential to influence evolving fetal structure and function. There has been substantial progress in understanding the epigenetic mechanisms through which environmental exposures can permanently alter the expression of fetal genes and contribute to the increasing propensity for many complex diseases. These concepts of ""developmental origins"" of disease are being applied across virtually all fields of medicine, and emerging epigenetic paradigms are the likely mechanism behind the environment-driven epidemic of asthma and allergic disease. Here, we examine the epigenetic regulation of immune development and the early immune profiles that contribute to allergic risk. In particular we review new evidence that key environmental exposures, such as microbial exposure, dietary changes, tobacco smoke, and pollutants, can induce epigenetic changes in gene expression and alter disease risk. Although most of these factors have already been clearly implicated in epidemiologic studies of asthma and allergic disease, new studies investigating the mechanisms of these effects may provide new avenues for using these pathways for disease prevention. CHEST 2011; 139(3):640-647"	67	103	2011	8	10.1378/chest.10-1800	General & Internal Medicine; Respiratory System
EXPOSURE TO PHTHALATES: REPRODUCTIVE OUTCOME AND CHILDREN HEALTH. A REVIEW OF EPIDEMIOLOGICAL STUDIES. Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children's neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary levels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.. exposure to phthalates| children health| reproductive outcome|in-utero exposure| school-age-children| n-butyl phthalate| anogenital distance| semen quality| di(2-ethylhexyl) phthalate| urinary concentrations| endocrine disruptors| bis(2-ethylhexyl) phthalate| environmental chemicals.	2011	exposure to phthalates| children health| reproductive outcome|in-utero exposure| school-age-children| n-butyl phthalate| anogenital distance| semen quality| di(2-ethylhexyl) phthalate| urinary concentrations| endocrine disruptors| bis(2-ethylhexyl) phthalate| environmental chemicals	Jurewicz, J; Hanke, W	EXPOSURE TO PHTHALATES: REPRODUCTIVE OUTCOME AND CHILDREN HEALTH. A REVIEW OF EPIDEMIOLOGICAL STUDIES		INTERNATIONAL JOURNAL OF OCCUPATIONAL MEDICINE AND ENVIRONMENTAL HEALTH	Exposure to phthalates; Children health; Reproductive outcome	IN-UTERO EXPOSURE; SCHOOL-AGE-CHILDREN; N-BUTYL PHTHALATE; ANOGENITAL DISTANCE; SEMEN QUALITY; DI(2-ETHYLHEXYL) PHTHALATE; URINARY CONCENTRATIONS; ENDOCRINE DISRUPTORS; BIS(2-ETHYLHEXYL) PHTHALATE; ENVIRONMENTAL CHEMICALS	Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children's neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary levels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.	90	103	2011	27	10.2478/s13382-011-0022-2	Public, Environmental & Occupational Health
Shellfish allergy. Seafood plays an important role in human nutrition and health. The growing international trade in seafood species and products has added to the popularity and frequency of consumption of a variety of seafood products across many countries. This increased production and consumption of seafood has been accompanied by more frequent reports of adverse health problems among consumers as well as processors of seafood. Adverse reactions to seafood are often generated by contaminants but can also be mediated by the immune system and cause allergies. These reactions can result from exposure to the seafood itself or various non-seafood components in the product. Non-immunological reactions to seafood can be triggered by contaminants such as parasites, bacteria, viruses, marine toxins and biogenic amines. Ingredients added during processing and canning of seafood can also cause adverse reactions. Importantly all these substances are able to trigger symptoms which are similar to true allergic reactions, which are mediated by antibodies produced by the immune system against specific allergens. Allergic reactions to 'shellfish', which comprises the groups of crustaceans and molluscs, can generate clinical symptoms ranging from mild urticaria and oral allergy syndrome to life-threatening anaphylactic reactions. The prevalence of crustacean allergy seems to vary largely between geographical locations, most probably as a result of the availability of seafood. The major shellfish allergen is tropomyosin, although other allergens may play an important part in allergenicity such as arginine kinase and myosin light chain. Current observations regard tropomyosin to be the major allergen responsible for molecular and clinical cross-reactivity between crustaceans and molluscs, but also to other inhaled invertebrates such as house dust mites and insects. Future research on the molecular structure of tropomyosins with a focus on the immunological and particularly clinical cross-reactivity will improve diagnosis and management of this potentially life-threatening allergy and is essential for future immunotherapy.. house-dust-mite| major shrimp allergen| invertebrate pan-allergen| cross-reactive allergen| calcium-binding protein| fish processing workers| pen a-1 tropomyosin| seafood allergy| food allergy| anisakis-simplex.	JUN-2010	house-dust-mite| major shrimp allergen| invertebrate pan-allergen| cross-reactive allergen| calcium-binding protein| fish processing workers| pen a-1 tropomyosin| seafood allergy| food allergy| anisakis-simplex	Lopata, AL; O'Hehir, RE; Lehrer, SB	Shellfish allergy		CLINICAL AND EXPERIMENTAL ALLERGY		HOUSE-DUST-MITE; MAJOR SHRIMP ALLERGEN; INVERTEBRATE PAN-ALLERGEN; CROSS-REACTIVE ALLERGEN; CALCIUM-BINDING PROTEIN; FISH PROCESSING WORKERS; PEN A-1 TROPOMYOSIN; SEAFOOD ALLERGY; FOOD ALLERGY; ANISAKIS-SIMPLEX	Seafood plays an important role in human nutrition and health. The growing international trade in seafood species and products has added to the popularity and frequency of consumption of a variety of seafood products across many countries. This increased production and consumption of seafood has been accompanied by more frequent reports of adverse health problems among consumers as well as processors of seafood. Adverse reactions to seafood are often generated by contaminants but can also be mediated by the immune system and cause allergies. These reactions can result from exposure to the seafood itself or various non-seafood components in the product. Non-immunological reactions to seafood can be triggered by contaminants such as parasites, bacteria, viruses, marine toxins and biogenic amines. Ingredients added during processing and canning of seafood can also cause adverse reactions. Importantly all these substances are able to trigger symptoms which are similar to true allergic reactions, which are mediated by antibodies produced by the immune system against specific allergens. Allergic reactions to 'shellfish', which comprises the groups of crustaceans and molluscs, can generate clinical symptoms ranging from mild urticaria and oral allergy syndrome to life-threatening anaphylactic reactions. The prevalence of crustacean allergy seems to vary largely between geographical locations, most probably as a result of the availability of seafood. The major shellfish allergen is tropomyosin, although other allergens may play an important part in allergenicity such as arginine kinase and myosin light chain. Current observations regard tropomyosin to be the major allergen responsible for molecular and clinical cross-reactivity between crustaceans and molluscs, but also to other inhaled invertebrates such as house dust mites and insects. Future research on the molecular structure of tropomyosins with a focus on the immunological and particularly clinical cross-reactivity will improve diagnosis and management of this potentially life-threatening allergy and is essential for future immunotherapy.	89	103	2010	9	10.1111/j.1365-2222.2010.03513.x	Allergy; Immunology
Effect of diet on asthma and allergic sensitisation in the International Study on Allergies and Asthma in Childhood (ISAAC) Phase Two. Background The increasing prevalence of asthma and allergy might be related to diet, particularly in Western countries. A study was undertaken to assess the association between dietary factors, asthma and allergy in a large international study including objective measurements of atopy. Methods Between 1995 and 2005, cross-sectional studies were performed in 29 centres in 20 countries. Parental questionnaires were used to collect information on allergic diseases and exposure factors and data from 50 004 randomly selected schoolchildren (8-12 years, 29 579 with skin prick testing) were analysed. Random effect models for meta-analysis were applied to calculate combined ORs. Results Fruit intake was associated with a low prevalence of current wheeze in affluent (OR(adj) 0.86, 95% CI 0.73 to 1.02) and non-affluent countries (OR(adj) 0.71, 95% CI 0.57 to 0.88). Consumption of fish in affluent countries (OR(adj) 0.85, 95% CI 0.74 to 0.97) and of cooked green vegetables in non-affluent countries (OR(adj) 0.78, 95% CI 0.65 to 0.95) was associated with a lower prevalence of current wheeze. Overall, more frequent consumption of fruit, vegetables and fish was associated with a lower lifetime prevalence of asthma, whereas high burger consumption was associated with higher lifetime asthma prevalence. None of the food items was associated with allergic sensitisation. Except for fruit juice and fruit consumption, no associations were found with atopic wheeze. Food selection according to the 'Mediterranean diet' was associated with a lower prevalence of current wheeze and asthma ever (p(trend)=0.03). Conclusion Diet is associated with wheeze and asthma but not with allergic sensitisation in children. These results provide further evidence that adherence to the 'Mediterranean diet' may provide some protection against wheeze and asthma in childhood.. mediterranean diet| fatty-acids| vitamin-c| antioxidant vitamin| symptom prevalence| pulmonary-function| school-children| lung-function| serum levels| risk-factor.	JUN-2010	mediterranean diet| fatty-acids| vitamin-c| antioxidant vitamin| symptom prevalence| pulmonary-function| school-children| lung-function| serum levels| risk-factor	Nagel, G; Weinmayr, G; Kleiner, A; Garcia-Marcos, L; Strachan, DP	Effect of diet on asthma and allergic sensitisation in the International Study on Allergies and Asthma in Childhood (ISAAC) Phase Two		THORAX		MEDITERRANEAN DIET; FATTY-ACIDS; VITAMIN-C; ANTIOXIDANT VITAMIN; SYMPTOM PREVALENCE; PULMONARY-FUNCTION; SCHOOL-CHILDREN; LUNG-FUNCTION; SERUM LEVELS; RISK-FACTOR	Background The increasing prevalence of asthma and allergy might be related to diet, particularly in Western countries. A study was undertaken to assess the association between dietary factors, asthma and allergy in a large international study including objective measurements of atopy. Methods Between 1995 and 2005, cross-sectional studies were performed in 29 centres in 20 countries. Parental questionnaires were used to collect information on allergic diseases and exposure factors and data from 50 004 randomly selected schoolchildren (8-12 years, 29 579 with skin prick testing) were analysed. Random effect models for meta-analysis were applied to calculate combined ORs. Results Fruit intake was associated with a low prevalence of current wheeze in affluent (OR(adj) 0.86, 95% CI 0.73 to 1.02) and non-affluent countries (OR(adj) 0.71, 95% CI 0.57 to 0.88). Consumption of fish in affluent countries (OR(adj) 0.85, 95% CI 0.74 to 0.97) and of cooked green vegetables in non-affluent countries (OR(adj) 0.78, 95% CI 0.65 to 0.95) was associated with a lower prevalence of current wheeze. Overall, more frequent consumption of fruit, vegetables and fish was associated with a lower lifetime prevalence of asthma, whereas high burger consumption was associated with higher lifetime asthma prevalence. None of the food items was associated with allergic sensitisation. Except for fruit juice and fruit consumption, no associations were found with atopic wheeze. Food selection according to the 'Mediterranean diet' was associated with a lower prevalence of current wheeze and asthma ever (p(trend)=0.03). Conclusion Diet is associated with wheeze and asthma but not with allergic sensitisation in children. These results provide further evidence that adherence to the 'Mediterranean diet' may provide some protection against wheeze and asthma in childhood.	36	103	2010	7	10.1136/thx.2009.128256	Respiratory System
From Allergen Genes to Allergy Vaccines. IgE-mediated allergy is a hypersensitivity disease affecting more than 25% of the population. The structures of the most common allergens have been revealed through molecular cloning technology in the past two decades. On the basis of this knowledge of the sequences and three-dimensional structures of culprit allergens, investigators can now analyze the immune recognition of allergens and the mechanisms of allergic inflammation in allergic patients. Allergy vaccines have been constructed that are able to selectively target the aberrant immune responses in allergic patients via different pathways of the immune system. Here we review various types of allergy vaccines that have been developed based on allergen structures, results from their clinical application in allergic patients, and future strategies for allergen-specific immunotherapy and allergy prophylaxis.. allergy| recombinant allergen| specific immunotherapy| ige| t cell| peptide| diagnosis|birch-pollen allergen| house-dust mite| bet v 1| t-cell epitope| late asthmatic reactions| short ragweed allergen| fc-epsilon-ri| phl p 5| overlapping synthetic peptides| randomized controlled-trial.	2010	allergy| recombinant allergen| specific immunotherapy| ige| t cell| peptide| diagnosis|birch-pollen allergen| house-dust mite| bet v 1| t-cell epitope| late asthmatic reactions| short ragweed allergen| fc-epsilon-ri| phl p 5| overlapping synthetic peptides| randomized controlled-trial	Valenta, R; Ferreira, F; Focke-Tejkl, M; Linhart, B; Niederberger, V; Swoboda, I; Vrtala, S	From Allergen Genes to Allergy Vaccines		ANNUAL REVIEW OF IMMUNOLOGY, VOL 28	allergy; recombinant allergen; specific immunotherapy; IgE; T cell; peptide; diagnosis	BIRCH-POLLEN ALLERGEN; HOUSE-DUST MITE; BET V 1; T-CELL EPITOPE; LATE ASTHMATIC REACTIONS; SHORT RAGWEED ALLERGEN; FC-EPSILON-RI; PHL P 5; OVERLAPPING SYNTHETIC PEPTIDES; RANDOMIZED CONTROLLED-TRIAL	IgE-mediated allergy is a hypersensitivity disease affecting more than 25% of the population. The structures of the most common allergens have been revealed through molecular cloning technology in the past two decades. On the basis of this knowledge of the sequences and three-dimensional structures of culprit allergens, investigators can now analyze the immune recognition of allergens and the mechanisms of allergic inflammation in allergic patients. Allergy vaccines have been constructed that are able to selectively target the aberrant immune responses in allergic patients via different pathways of the immune system. Here we review various types of allergy vaccines that have been developed based on allergen structures, results from their clinical application in allergic patients, and future strategies for allergen-specific immunotherapy and allergy prophylaxis.	241	103	2010	31	10.1146/annurev-immunol-030409-101218	Immunology
In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects. Background: Human rhinoviruses (HRVs) characteristically cause upper respiratory tract infection, but they also infect the lower airways, causing acute bronchitis and exacerbating asthma. Objective: Our purpose was to study ex vivo the differences in the response to HRV infection of nasal and bronchial epithelial cultures from the same healthy and asthmatic individuals using conditions favoring development of fully differentiated, pseudostratified mucociliary epithelium. Methods: Cells from the inferior turbinates and bronchial tree of 5 healthy and 6 asthmatic individuals were cultured at an air-liquid interface. Cultures were infected with HRV-16, and after 48 hours, the degree of infection was measured. Results: Baseline median transepithelial resistance was lower in human bronchial epithelial (HBE) cell cultures than in human nasal epithelial (HNE) cell cultures (195 Omega.cm(2) [95% CI, 164-252] vs 366 Omega.cm(2) [95% CI, 234-408], respectively; P < .01). Virus replicated more easily in HBE cells than in HNE cells based on virus shedding in apical wash (log tissue culture infective dose of 50%/0.1 mL = 2.0 [95% CI, 1.0-2.5] vs 0.5 [95% CI, 0.5-1.5], P < .01) and on a 20- to 30-fold greater viral load and number of infected cells in HBE cell cultures than in FINE cell cultures. The increases in expression of RANTES and double-stranded RNA-dependent protein kinase were greater in HBE cell cultures than in HNE cell cultures, as were the concentrations of IL-8, IL-1 alpha, RANTES, and IP-10 in basolateral medium. However, no significant differences between asthmatic and healthy subjects (including IFN-beta 1 expression) were found. Conclusions: Differentiated nasal epithelial cells might have mechanisms of increased resistance to rhinovirus infection compared with bronchial epithelial cells. We could not confirm previous reports of increased susceptibility to HRV infection in epithelial cells from asthmatic subjects. (J Allergy Clin Immunol 2009;123:1384-90.). human rhinovirus| nasal and bronchial airway epithelial cells| air-liquid interface|human tracheal epithelium| bioelectric properties| situ hybridization| cultures| asthma| exacerbations| expression| differentiation| replication| disease.	JUN-2009	human rhinovirus| nasal and bronchial airway epithelial cells| air-liquid interface|human tracheal epithelium| bioelectric properties| situ hybridization| cultures| asthma| exacerbations| expression| differentiation| replication| disease	Lopez-Souza, N; Favoreto, S; Wong, H; Ward, T; Yagi, S; Schnurr, D; Finkbeiner, WE; Dolganov, GM; Widdicombe, JH; Boushey, HA; Avila, PC	In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Human rhinovirus; nasal and bronchial airway epithelial cells; air-liquid interface	HUMAN TRACHEAL EPITHELIUM; BIOELECTRIC PROPERTIES; SITU HYBRIDIZATION; CULTURES; ASTHMA; EXACERBATIONS; EXPRESSION; DIFFERENTIATION; REPLICATION; DISEASE	Background: Human rhinoviruses (HRVs) characteristically cause upper respiratory tract infection, but they also infect the lower airways, causing acute bronchitis and exacerbating asthma. Objective: Our purpose was to study ex vivo the differences in the response to HRV infection of nasal and bronchial epithelial cultures from the same healthy and asthmatic individuals using conditions favoring development of fully differentiated, pseudostratified mucociliary epithelium. Methods: Cells from the inferior turbinates and bronchial tree of 5 healthy and 6 asthmatic individuals were cultured at an air-liquid interface. Cultures were infected with HRV-16, and after 48 hours, the degree of infection was measured. Results: Baseline median transepithelial resistance was lower in human bronchial epithelial (HBE) cell cultures than in human nasal epithelial (HNE) cell cultures (195 Omega.cm(2) [95% CI, 164-252] vs 366 Omega.cm(2) [95% CI, 234-408], respectively; P < .01). Virus replicated more easily in HBE cells than in HNE cells based on virus shedding in apical wash (log tissue culture infective dose of 50%/0.1 mL = 2.0 [95% CI, 1.0-2.5] vs 0.5 [95% CI, 0.5-1.5], P < .01) and on a 20- to 30-fold greater viral load and number of infected cells in HBE cell cultures than in FINE cell cultures. The increases in expression of RANTES and double-stranded RNA-dependent protein kinase were greater in HBE cell cultures than in HNE cell cultures, as were the concentrations of IL-8, IL-1 alpha, RANTES, and IP-10 in basolateral medium. However, no significant differences between asthmatic and healthy subjects (including IFN-beta 1 expression) were found. Conclusions: Differentiated nasal epithelial cells might have mechanisms of increased resistance to rhinovirus infection compared with bronchial epithelial cells. We could not confirm previous reports of increased susceptibility to HRV infection in epithelial cells from asthmatic subjects. (J Allergy Clin Immunol 2009;123:1384-90.)	37	103	2009	7	10.1016/j.jaci.2009.03.010	Allergy; Immunology
"Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases. Inhaled air is contaminated with pathogens and particulates that may deposit in the airways and damage the host. In response to these invaders, the airway epithelium has developed innate immune responses that provide a defence against the invaders and protect the airway structure and function. Thus, the epithelium of conducting airways becomes the ""battleground"" between the invaders and the host. Recent evidence suggests that airway epithelial surface signalling through the epidermal growth factor receptor (EGFR) is a convergent pathway producing innate immune responses to a variety of infectious and noninfectious noxious stimuli. In the present review, the EGFR signalling pathways leading to airway mucin production, neutrophil recruitment (via interleukin-8 production) and airway epithelial repair were examined. The importance of these findings in human airway diseases was also investigated. The current authors suggest that the exaggerated innate immune responses found in chronic inflammatory airway diseases (e.g. chronic obstructive pulmonary disease, cystic fibrosis and severe asthma) contribute to the pathogenesis or the aggravation of these diseases. Potential therapies include inhibition of the various elements of the described epidermal growth factor receptor cascade. In considering each therapeutic intervention, the potential benefits must be considered in relation to potential deleterious effects.. asthma| chronic obstructive pulmonary disease| cystic fibrosis| interleukin-8| mucins| neutrophils|obstructive pulmonary-disease| necrosis-factor-alpha| mucin gene-expression| protein-coupled receptors| goblet cell hyperplasia| respiratory epithelial-cells| activating-factor receptor| gram-negative bacteria| c-erbb receptors| nf-kappa-b."	OCT-2008	asthma| chronic obstructive pulmonary disease| cystic fibrosis| interleukin-8| mucins| neutrophils|obstructive pulmonary-disease| necrosis-factor-alpha| mucin gene-expression| protein-coupled receptors| goblet cell hyperplasia| respiratory epithelial-cells| activating-factor receptor| gram-negative bacteria| c-erbb receptors| nf-kappa-b	Burgel, PR; Nadel, JA	Epidermal growth factor receptor-mediated innate immune responses and their roles in airway diseases		EUROPEAN RESPIRATORY JOURNAL	asthma; chronic obstructive pulmonary disease; cystic fibrosis; interleukin-8; mucins; neutrophils	OBSTRUCTIVE PULMONARY-DISEASE; NECROSIS-FACTOR-ALPHA; MUCIN GENE-EXPRESSION; PROTEIN-COUPLED RECEPTORS; GOBLET CELL HYPERPLASIA; RESPIRATORY EPITHELIAL-CELLS; ACTIVATING-FACTOR RECEPTOR; GRAM-NEGATIVE BACTERIA; C-ERBB RECEPTORS; NF-KAPPA-B	"Inhaled air is contaminated with pathogens and particulates that may deposit in the airways and damage the host. In response to these invaders, the airway epithelium has developed innate immune responses that provide a defence against the invaders and protect the airway structure and function. Thus, the epithelium of conducting airways becomes the ""battleground"" between the invaders and the host. Recent evidence suggests that airway epithelial surface signalling through the epidermal growth factor receptor (EGFR) is a convergent pathway producing innate immune responses to a variety of infectious and noninfectious noxious stimuli. In the present review, the EGFR signalling pathways leading to airway mucin production, neutrophil recruitment (via interleukin-8 production) and airway epithelial repair were examined. The importance of these findings in human airway diseases was also investigated. The current authors suggest that the exaggerated innate immune responses found in chronic inflammatory airway diseases (e.g. chronic obstructive pulmonary disease, cystic fibrosis and severe asthma) contribute to the pathogenesis or the aggravation of these diseases. Potential therapies include inhibition of the various elements of the described epidermal growth factor receptor cascade. In considering each therapeutic intervention, the potential benefits must be considered in relation to potential deleterious effects."	166	103	2008	14	10.1183/09031936.00172007	Respiratory System
The CREATE Project: development of certified reference materials for allergenic products and validation of methods for their quantification. Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE-binding potencies as their focus. Unfortunately, each company is using their own in-house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.. 1st international standard| small-angle scattering| dust mite allergen| dermatophagoides-pteronyssinus| immunological response| recombinant allergens| circular-dichroism| mass-spectrometry| indoor allergens| computer-program.	MAR-2008	1st international standard| small-angle scattering| dust mite allergen| dermatophagoides-pteronyssinus| immunological response| recombinant allergens| circular-dichroism| mass-spectrometry| indoor allergens| computer-program	Van Ree, R; Chapman, MD; Ferreira, F; Vieths, S; Bryan, D; Cromwell, O; Villalba, M; Durham, SR; Becker, WM; Aalbers, M; Andre, C; Barber, D; Bahima, AC; Custovic, A; Didierlaurent, A; Dolman, C; Dorpema, JW; Di Felice, G; Eberhardt, F; Fernandez Caldas, E; Fernandez Rivas, M; Fiebig, H; Focke, M; Fotisch, K; Gadermaier, G; Das, RG; Gonzalez Mancebo, E; Himly, M; Kinaciyan, T; Knulst, AC; Kroon, AM; Lepp, U; Marco, FM; Mari, A; Moingeon, P; Monsalve, R; Neubauer, A; Notten, S; Heer, PO; Pauli, G; Pini, C; Purohit, A; Quiralte, J; Rak, S; Raulf-Heimsoth, M; SanMiguel Moncin, MM; Simpson, B; Tsay, A; Vailes, L; Wallner, M; Weber, B	The CREATE Project: development of certified reference materials for allergenic products and validation of methods for their quantification		ALLERGY		1ST INTERNATIONAL STANDARD; SMALL-ANGLE SCATTERING; DUST MITE ALLERGEN; DERMATOPHAGOIDES-PTERONYSSINUS; IMMUNOLOGICAL RESPONSE; RECOMBINANT ALLERGENS; CIRCULAR-DICHROISM; MASS-SPECTROMETRY; INDOOR ALLERGENS; COMPUTER-PROGRAM	Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE-binding potencies as their focus. Unfortunately, each company is using their own in-house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.	44	103	2008	17	10.1111/j.1398-9995.2007.01612.x	Allergy; Immunology
Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development. Immune system development, particularly in the prenatal period, has far-reaching consequences for health during early childhood, as well as throughout life. Environmental disturbance of the complex balances of Th1 and Th2 response mechanisms can alter that normal development. Dysregulation of this process or an aberrant trajectory or timing of events can result in atopy, asthma, a compromised ability to ward off infection, or other auto-immune disease. A wide range of chemical, physical and biological agents appear to be capable of disrupting immune development. This MiniReview briefly reviews developmental milestones of the immune system in the prenatal period and early life, and then presents examples of environmentally induced alterations in immune markers. The first example involves a birth cohort study linked to an extensive programme of air pollution monitoring; the analysis shows prenatal ambient polycyclic aromatic hydrocarbons (PAH) and fine particle (PM2.5) exposures to be associated with altered lymphocyte immunophenotypic distributions in cord blood and possible changes in cord serum immunoglobulin E levels. The second example is a study of prenatal-polychlorinated biphenyl (PCB) exposures and the foetal development of the thymus, the organ responsible for lymphocyte maturation. Mothers with higher serum concentrations of PCBs gave birth to neonates having smaller indices of thymus size. Finally, this report underscores the tight connection between development of the immune system and that of the central nervous system, and the plausibility that disruption of critical events in immune development may play a role in neurobehavioural disorders.. environmental tobacco-smoke| interferon-gamma production| in-vitro exposure| polychlorinated-biphenyls| critical windows| cord-blood| childrens health| ultrafine particles| autoimmune-disease| congenital-rubella.	FEB-2008	environmental tobacco-smoke| interferon-gamma production| in-vitro exposure| polychlorinated-biphenyls| critical windows| cord-blood| childrens health| ultrafine particles| autoimmune-disease| congenital-rubella	Hertz-Picciotto, I; Park, HY; Dostal, M; Kocan, A; Trnovec, T; Sram, R	Prenatal exposures to persistent and non-persistent organic compounds and effects on immune system development		BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY		ENVIRONMENTAL TOBACCO-SMOKE; INTERFERON-GAMMA PRODUCTION; IN-VITRO EXPOSURE; POLYCHLORINATED-BIPHENYLS; CRITICAL WINDOWS; CORD-BLOOD; CHILDRENS HEALTH; ULTRAFINE PARTICLES; AUTOIMMUNE-DISEASE; CONGENITAL-RUBELLA	Immune system development, particularly in the prenatal period, has far-reaching consequences for health during early childhood, as well as throughout life. Environmental disturbance of the complex balances of Th1 and Th2 response mechanisms can alter that normal development. Dysregulation of this process or an aberrant trajectory or timing of events can result in atopy, asthma, a compromised ability to ward off infection, or other auto-immune disease. A wide range of chemical, physical and biological agents appear to be capable of disrupting immune development. This MiniReview briefly reviews developmental milestones of the immune system in the prenatal period and early life, and then presents examples of environmentally induced alterations in immune markers. The first example involves a birth cohort study linked to an extensive programme of air pollution monitoring; the analysis shows prenatal ambient polycyclic aromatic hydrocarbons (PAH) and fine particle (PM2.5) exposures to be associated with altered lymphocyte immunophenotypic distributions in cord blood and possible changes in cord serum immunoglobulin E levels. The second example is a study of prenatal-polychlorinated biphenyl (PCB) exposures and the foetal development of the thymus, the organ responsible for lymphocyte maturation. Mothers with higher serum concentrations of PCBs gave birth to neonates having smaller indices of thymus size. Finally, this report underscores the tight connection between development of the immune system and that of the central nervous system, and the plausibility that disruption of critical events in immune development may play a role in neurobehavioural disorders.	83	103	2008	9	10.1111/j.1742-7843.2007.00190.x	Pharmacology & Pharmacy; Toxicology
"Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses. Infants of smokers have much higher rates of respiratory infection, asthma and airway disease. The current study assessed the effects of maternal smoking in pregnancy on neonatal toll-like-receptor (TLR)-mediated immune responses as a possible contributing factor to the elevated rates of respiratory illness. In a prospective birth cohort, the cord blood immune responses of neonates of smoking and nonsmoking mothers were compared. Maternal and cord serum cotinine were measured to confirm the level of cigarette smoke exposure. Neonatal cytokine responses were assessed to optimal doses of TILR2, TLR3, TLR4 and TLR9 ligands. Cotinine levels confirmed maternal reporting of cigarette smoking in pregnancy, with significantly higher cotinine levels in maternal and cord blood compared with the nonsmoking group. Infants of smoking mothers showed significantly attenuated innate TLR-mediated responses compared with infants of nonsmokers. The current findings indicate that in addition to effects on developing airways, maternal smoking also has significant immunological effects in pregnancy, which could contribute to the well recognised, subsequent increased risk of respiratory infections and asthma. These effects appear to be mediated through effects on toll-like receptor-mediated innate response pathways, which also promote regulatory pathways in the inhibition of allergic immune responses in the postnatal period, suggesting that other environmental interactions are highly relevant to the ""hygiene hypothesis"".. cord blood| cotinine| cytokines| innate immunity| smoking| toll-like receptors|environmental tobacco-smoke| bronchial epithelial-cells| respiratory-infections| inhalant allergen| dendritic cells| early-childhood| lipopolysaccharide| exposure| expression| responsiveness."	OCT-2006	cord blood| cotinine| cytokines| innate immunity| smoking| toll-like receptors|environmental tobacco-smoke| bronchial epithelial-cells| respiratory-infections| inhalant allergen| dendritic cells| early-childhood| lipopolysaccharide| exposure| expression| responsiveness	Noakes, PS; Hale, J; Thomas, R; Lane, C; Devadason, SG; Prescott, SL	Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses		EUROPEAN RESPIRATORY JOURNAL	cord blood; cotinine; cytokines; innate immunity; smoking; toll-like receptors	ENVIRONMENTAL TOBACCO-SMOKE; BRONCHIAL EPITHELIAL-CELLS; RESPIRATORY-INFECTIONS; INHALANT ALLERGEN; DENDRITIC CELLS; EARLY-CHILDHOOD; LIPOPOLYSACCHARIDE; EXPOSURE; EXPRESSION; RESPONSIVENESS	"Infants of smokers have much higher rates of respiratory infection, asthma and airway disease. The current study assessed the effects of maternal smoking in pregnancy on neonatal toll-like-receptor (TLR)-mediated immune responses as a possible contributing factor to the elevated rates of respiratory illness. In a prospective birth cohort, the cord blood immune responses of neonates of smoking and nonsmoking mothers were compared. Maternal and cord serum cotinine were measured to confirm the level of cigarette smoke exposure. Neonatal cytokine responses were assessed to optimal doses of TILR2, TLR3, TLR4 and TLR9 ligands. Cotinine levels confirmed maternal reporting of cigarette smoking in pregnancy, with significantly higher cotinine levels in maternal and cord blood compared with the nonsmoking group. Infants of smoking mothers showed significantly attenuated innate TLR-mediated responses compared with infants of nonsmokers. The current findings indicate that in addition to effects on developing airways, maternal smoking also has significant immunological effects in pregnancy, which could contribute to the well recognised, subsequent increased risk of respiratory infections and asthma. These effects appear to be mediated through effects on toll-like receptor-mediated innate response pathways, which also promote regulatory pathways in the inhibition of allergic immune responses in the postnatal period, suggesting that other environmental interactions are highly relevant to the ""hygiene hypothesis""."	35	103	2006	9	10.1183/09031936.06.00050206	Respiratory System
Biological material on inhaled coarse fraction particulate matter activates airway phagocytes in vivo in healthy volunteers. Background: In vitro, endotoxin on coarse fraction particulate matter (PM2.5-10) accounts for the majority of the ability of PM2.5-10 to induce cytokine responses from alveolar macrophages. Objective: We examined in vivo whether inhaled PM2.5-10 from local ambient air induce inflammatory and immune responses in the airways of healthy human beings and whether biologic material on PM2.5-10 accounts for these effects. Methods: On 3 separate visits, 9 healthy subjects inhaled nebulized saline (0.9%, control), PM2.5-10 collected from local ambient air that was heated to inactivate biological material (PM2.5-10-), or nonheated PM (PM2.5-10+)- PM2.5-10 deposition (similar to 0.65 mg/subject) targeted the bronchial airways (confirmed by using radiolabeled aerosol), and induced sputum was obtained 2 to 3 hours postinhalation for analysis of cellular and biochemical markers of inflammation and innate immune function. Results: Inhaled PM2.5-10+ induced elevated inflammation (% PMNs, macrophage mRNA TNF-alpha), increased eotaxin, upregulated immune surface phenotypes on macrophages (mCD14, CD11b, HLA-DR), and increased phagocytosis (monocytes) versus saline (P < .05). Biological inactivation of PM2.5-10 (PM2.5-10-) had no effect on neutrophilia but significantly (P < .05) attenuated mRNA TNF-alpha, eotaxin levels, cell surface marker responses, and phagocytosis. Conclusion: Biological components of PM2.5-10 are not necessary to induce neutrophil responses but are essential in mediating macrophage responses. The ability Of PM2.5-10 to activate monocytic cells and potentially skew the airways toward an allergic phenotype by enhancing eotaxin levels may enhance responses to allergens or bacteria in individuals with allergy. Clinical implications: PM2.5-10 might enhance the response of individuals with allergy to airborne bacteria.. pm(2.5-1)0| airway macrophages| tnf-alpha| mcd14| eotaxin|alveolar macrophage responses| diesel exhaust particles| pollution particles| insoluble components| atopic asthmatics| endotoxin| exposure| inflammation| deposition| ultrafine.	JUN-2006	pm(2.5-1)0| airway macrophages| tnf-alpha| mcd14| eotaxin|alveolar macrophage responses| diesel exhaust particles| pollution particles| insoluble components| atopic asthmatics| endotoxin| exposure| inflammation| deposition| ultrafine	Alexis, NE; Lay, JC; Zeman, K; Bennett, WE; Peden, DB; Soukup, JM; Devlin, RB; Becker, S	Biological material on inhaled coarse fraction particulate matter activates airway phagocytes in vivo in healthy volunteers		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	PM(2.5-1)0; airway macrophages; TNF-alpha; mCD14; eotaxin	ALVEOLAR MACROPHAGE RESPONSES; DIESEL EXHAUST PARTICLES; POLLUTION PARTICLES; INSOLUBLE COMPONENTS; ATOPIC ASTHMATICS; ENDOTOXIN; EXPOSURE; INFLAMMATION; DEPOSITION; ULTRAFINE	Background: In vitro, endotoxin on coarse fraction particulate matter (PM2.5-10) accounts for the majority of the ability of PM2.5-10 to induce cytokine responses from alveolar macrophages. Objective: We examined in vivo whether inhaled PM2.5-10 from local ambient air induce inflammatory and immune responses in the airways of healthy human beings and whether biologic material on PM2.5-10 accounts for these effects. Methods: On 3 separate visits, 9 healthy subjects inhaled nebulized saline (0.9%, control), PM2.5-10 collected from local ambient air that was heated to inactivate biological material (PM2.5-10-), or nonheated PM (PM2.5-10+)- PM2.5-10 deposition (similar to 0.65 mg/subject) targeted the bronchial airways (confirmed by using radiolabeled aerosol), and induced sputum was obtained 2 to 3 hours postinhalation for analysis of cellular and biochemical markers of inflammation and innate immune function. Results: Inhaled PM2.5-10+ induced elevated inflammation (% PMNs, macrophage mRNA TNF-alpha), increased eotaxin, upregulated immune surface phenotypes on macrophages (mCD14, CD11b, HLA-DR), and increased phagocytosis (monocytes) versus saline (P < .05). Biological inactivation of PM2.5-10 (PM2.5-10-) had no effect on neutrophilia but significantly (P < .05) attenuated mRNA TNF-alpha, eotaxin levels, cell surface marker responses, and phagocytosis. Conclusion: Biological components of PM2.5-10 are not necessary to induce neutrophil responses but are essential in mediating macrophage responses. The ability Of PM2.5-10 to activate monocytic cells and potentially skew the airways toward an allergic phenotype by enhancing eotaxin levels may enhance responses to allergens or bacteria in individuals with allergy. Clinical implications: PM2.5-10 might enhance the response of individuals with allergy to airborne bacteria.	32	103	2006	8	10.1016/j.jaci.2006.02.030	Allergy; Immunology
Home environmental intervention in inner-city asthma: a randomized controlled clinical trial. Background: Airborne pollutants and indoor allergens increase asthma morbidity in inner-city children; therefore, reducing exposure, if feasible, should improve asthma morbidity. Objective: To conduct a randomized controlled trial of methods to reduce environmental pollutant and allergen exposure in the homes of asthmatic children living in the inner city. Methods: After the completion of questionnaires, spirometry and allergen skin tests, home inspection, and measurement of home air pollutant and allergen levels, 100 asthmatic children aged 6 to 12 years were randomized to the treatment group (home-based education, cockroach and rodent extermination, mattress and pillow encasings, and high-efficiency particulate air cleaner) or to the control group (treated at the end of the I-year trial). Outcomes were evaluated by home evaluations at 6 and 12 months, clinic evaluation at 12 months, and multiple telephone interviews. Results: In the treatment group, 84% received cockroach extermination and 75% used the air cleaner. Levels of particulate matter 10 Am or smaller declined by LIP to 39% in the treatment group but increased in the control group (P < .001). Cockroach allergen levels decreased by 51% in the treatment group. Daytime symptoms increased in the control group and decreased in the treatment group (P = .04). Other measures of morbidity, such as spirometry findings, nighttime symptoms, and emergency department use, were not significantly changed. Conclusions: A tailored, multifaceted environmental treatment reduced airborne particulate matter and indoor allergen levels in inner-city homes, which, in turn, had a modest effect on morbidity.. cockroach allergen| air-pollution| children| exposure| particles| morbidity| abatement| smoking| filter.	DEC-2005	cockroach allergen| air-pollution| children| exposure| particles| morbidity| abatement| smoking| filter	Eggleston, PA; Butz, A; Rand, C; Curtin-Brosnan, J; Kanchanaraksa, S; Swartz, L; Breysse, P; Buckley, T; Diette, G; Merriman, B; Krishnan, JA	Home environmental intervention in inner-city asthma: a randomized controlled clinical trial		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		COCKROACH ALLERGEN; AIR-POLLUTION; CHILDREN; EXPOSURE; PARTICLES; MORBIDITY; ABATEMENT; SMOKING; FILTER	Background: Airborne pollutants and indoor allergens increase asthma morbidity in inner-city children; therefore, reducing exposure, if feasible, should improve asthma morbidity. Objective: To conduct a randomized controlled trial of methods to reduce environmental pollutant and allergen exposure in the homes of asthmatic children living in the inner city. Methods: After the completion of questionnaires, spirometry and allergen skin tests, home inspection, and measurement of home air pollutant and allergen levels, 100 asthmatic children aged 6 to 12 years were randomized to the treatment group (home-based education, cockroach and rodent extermination, mattress and pillow encasings, and high-efficiency particulate air cleaner) or to the control group (treated at the end of the I-year trial). Outcomes were evaluated by home evaluations at 6 and 12 months, clinic evaluation at 12 months, and multiple telephone interviews. Results: In the treatment group, 84% received cockroach extermination and 75% used the air cleaner. Levels of particulate matter 10 Am or smaller declined by LIP to 39% in the treatment group but increased in the control group (P < .001). Cockroach allergen levels decreased by 51% in the treatment group. Daytime symptoms increased in the control group and decreased in the treatment group (P = .04). Other measures of morbidity, such as spirometry findings, nighttime symptoms, and emergency department use, were not significantly changed. Conclusions: A tailored, multifaceted environmental treatment reduced airborne particulate matter and indoor allergen levels in inner-city homes, which, in turn, had a modest effect on morbidity.	35	103	2005	7		Allergy; Immunology
Asthma, chronic bronchitis, and exposure to irritant agents in occupational domestic cleaning: a nested case-control study. Background: Women employed in domestic cleaning are at increased risk for symptoms of obstructive lung disease, but the agents responsible are unknown. Aims: To investigate common tasks and products in occupational domestic cleaning in relation to respiratory morbidity. Methods: Case-control study in domestic cleaning women nested within a large population based survey of women aged 30-65 years; 160 domestic cleaning women with asthma symptoms, chronic bronchitis symptoms, or both and 386 without a history of respiratory symptoms were identified. Detailed exposures were evaluated for 40 cases who reported still having symptoms at the recruitment interview, and 155 controls who reported not having symptoms. All tasks performed and products used when cleaning houses were determined in a face-to-face interview. Lung function, methacholine challenge, and serum IgE testing were performed. Personal exposure measurements of airborne chlorine and ammonia were performed in a subsample. Associations between asthma, chronic bronchitis, and cleaning exposures were evaluated using multiple logistic regression analysis. Results: Airborne chlorine (median level 0-0.4 ppm) and ammonia (0.6-6.4 ppm) were detectable during occupational domestic cleaning activities. Cases used bleach more frequently than controls; adjusted odds ratio (OR) for intermediate exposure was 3.3 (95% CI 0.9 to 11) and for high exposure 4.9 (1.5 to 15). Other independent associations included accidental inhalation of vapours and gases from cleaning agents and washing dishes. These associations were more pronounced for cases with asthma symptoms than for those with symptoms of chronic bronchitis, but were not related to sensitisation to common allergens. Conclusions: Asthma symptoms in domestic cleaning women are associated with exposure to bleach and possibly other irritant agents. The public health impact of the use of irritant cleaning products could be widespread since the use of these products is common both in the workplace and at home.. respiratory-health-survey| airways dysfunction syndrome| work-related asthma| persistent asthma| symptoms| products| gas| responsiveness| experience| disease.	SEP-2005	respiratory-health-survey| airways dysfunction syndrome| work-related asthma| persistent asthma| symptoms| products| gas| responsiveness| experience| disease	Medina-Ramon, M; Zock, JP; Kogevinas, M; Sunyer, J; Torralba, Y; Borrell, A; Burgos, F; Anto, JM	Asthma, chronic bronchitis, and exposure to irritant agents in occupational domestic cleaning: a nested case-control study		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		RESPIRATORY-HEALTH-SURVEY; AIRWAYS DYSFUNCTION SYNDROME; WORK-RELATED ASTHMA; PERSISTENT ASTHMA; SYMPTOMS; PRODUCTS; GAS; RESPONSIVENESS; EXPERIENCE; DISEASE	Background: Women employed in domestic cleaning are at increased risk for symptoms of obstructive lung disease, but the agents responsible are unknown. Aims: To investigate common tasks and products in occupational domestic cleaning in relation to respiratory morbidity. Methods: Case-control study in domestic cleaning women nested within a large population based survey of women aged 30-65 years; 160 domestic cleaning women with asthma symptoms, chronic bronchitis symptoms, or both and 386 without a history of respiratory symptoms were identified. Detailed exposures were evaluated for 40 cases who reported still having symptoms at the recruitment interview, and 155 controls who reported not having symptoms. All tasks performed and products used when cleaning houses were determined in a face-to-face interview. Lung function, methacholine challenge, and serum IgE testing were performed. Personal exposure measurements of airborne chlorine and ammonia were performed in a subsample. Associations between asthma, chronic bronchitis, and cleaning exposures were evaluated using multiple logistic regression analysis. Results: Airborne chlorine (median level 0-0.4 ppm) and ammonia (0.6-6.4 ppm) were detectable during occupational domestic cleaning activities. Cases used bleach more frequently than controls; adjusted odds ratio (OR) for intermediate exposure was 3.3 (95% CI 0.9 to 11) and for high exposure 4.9 (1.5 to 15). Other independent associations included accidental inhalation of vapours and gases from cleaning agents and washing dishes. These associations were more pronounced for cases with asthma symptoms than for those with symptoms of chronic bronchitis, but were not related to sensitisation to common allergens. Conclusions: Asthma symptoms in domestic cleaning women are associated with exposure to bleach and possibly other irritant agents. The public health impact of the use of irritant cleaning products could be widespread since the use of these products is common both in the workplace and at home.	36	103	2005	9	10.1136/oem.2004.017640	Public, Environmental & Occupational Health
'Dampness' at home and its association with airway, nose, and skin symptoms among 10,851 preschool children in Sweden: a cross-sectional study. There is convincing epidemiological evidence that 'dampness' in buildings is associated with respiratory effects. In order to identify health-relevant exposures in buildings with 'dampness', the study 'Dampness in Buildings and Health' (DBH) was initiated. In the first step of the study, cross-sectional data on home characteristics including 'dampness' problems, and symptoms in airway, nose, and skin among 10,851 children (1-6 years), were collected by means of a questionnaire to the parents. The prevalence of wheezing during the last 12 months was 18.9% and doctor-diagnosed asthma 5.4%. Rhinitis during the last 12 months was reported for 11.1% of the children and eczema during the last 12 months 18.7%. Gender, allergic symptoms among parents, and age of the child were associated with symptoms. Water leakage was reported in 17.8% of the buildings, condensation on windows in 14.3%, and detached flooring materials in 8.3%. Visible mould or damp spots were reported in only 1.5% of the buildings. The four 'dampness' indices were associated to higher prevalence of symptoms in both crude and adjusted analysis. Furthermore, it was found that the combination of water leakage in the home and PVC as flooring material in the child's or parent's bedroom was associated to higher prevalence of symptoms among children. However, the interpretation of this finding is unclear. The combination of water leakage and PVC may be a proxy, for example, reconstruction because of water damages.. dampness| asthma| rhinitis| eczema| children|childhood asthma| bronchial obstruction| subtropical area| young-children| health| prevalence| buildings| exposure| bamse.	AUG-2005	dampness| asthma| rhinitis| eczema| children|childhood asthma| bronchial obstruction| subtropical area| young-children| health| prevalence| buildings| exposure| bamse	Bornehag, CG; Sundell, J; Hagerhed-Engman, L; Sigsggard, T; Janson, S; Aberg, N	'Dampness' at home and its association with airway, nose, and skin symptoms among 10,851 preschool children in Sweden: a cross-sectional study		INDOOR AIR	dampness; asthma; rhinitis; eczema; children	CHILDHOOD ASTHMA; BRONCHIAL OBSTRUCTION; SUBTROPICAL AREA; YOUNG-CHILDREN; HEALTH; PREVALENCE; BUILDINGS; EXPOSURE; BAMSE	There is convincing epidemiological evidence that 'dampness' in buildings is associated with respiratory effects. In order to identify health-relevant exposures in buildings with 'dampness', the study 'Dampness in Buildings and Health' (DBH) was initiated. In the first step of the study, cross-sectional data on home characteristics including 'dampness' problems, and symptoms in airway, nose, and skin among 10,851 children (1-6 years), were collected by means of a questionnaire to the parents. The prevalence of wheezing during the last 12 months was 18.9% and doctor-diagnosed asthma 5.4%. Rhinitis during the last 12 months was reported for 11.1% of the children and eczema during the last 12 months 18.7%. Gender, allergic symptoms among parents, and age of the child were associated with symptoms. Water leakage was reported in 17.8% of the buildings, condensation on windows in 14.3%, and detached flooring materials in 8.3%. Visible mould or damp spots were reported in only 1.5% of the buildings. The four 'dampness' indices were associated to higher prevalence of symptoms in both crude and adjusted analysis. Furthermore, it was found that the combination of water leakage in the home and PVC as flooring material in the child's or parent's bedroom was associated to higher prevalence of symptoms among children. However, the interpretation of this finding is unclear. The combination of water leakage and PVC may be a proxy, for example, reconstruction because of water damages.	13	103	2005	8	10.1111/j.1600-0668.2005.00306.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
A survey of occupational hand eczema in Denmark. Occupational hand eczema (OHE) is the most frequently recognized work-related disease in Denmark and the annual cost to society is high. Understanding of the epidemiology of OHE is essential to be able to give appropriate recommendations for its prevention. The study comprised 758 persons, 490 females and 268 males with recognized OHE in the period October 2001 to November 2002. Data were obtained prospectively from the National Board of Industrial Industry Registry and from a self-administered questionnaire (response rate, 82%). The most frequently recognized diagnosis was irritant contact dermatitis (ICD), mainly caused by wet occupations. The proportion of occupational ICD was equal for males and females, 59.7% and 63.1%, respectively. The estimated rates of OHE were high for bakers, hairdressers and dental surgery assistants, and a high proportion of apprentices were found among hairdressers. The prevalence of atopic dermatitis was low (16.4%) compared to previous studies among hand eczema patients. The prevalence of occupational allergic contact dermatitis in the study population was substantially higher among males than females, and the most frequent causes among males were allergy to chromium (leather exposure), rubber additives (gloves) and nickel due to exposure from work tools and metalworking industry.. allergic contact dermatitis| atopic dermatitis| contact urticaria| irritant contact dermatitis| occupational hand eczema| prevention| socio-economic impact|skin-disease| contact-dermatitis| risk-factors| allergy| population| prognosis| workers| nickel| dermatoses| prevalence.	OCT-2004	allergic contact dermatitis| atopic dermatitis| contact urticaria| irritant contact dermatitis| occupational hand eczema| prevention| socio-economic impact|skin-disease| contact-dermatitis| risk-factors| allergy| population| prognosis| workers| nickel| dermatoses| prevalence	Skoet, R; Olsen, J; Mathiesen, B; Iversen, L; Johansen, JD; Agner, T	A survey of occupational hand eczema in Denmark		CONTACT DERMATITIS	allergic contact dermatitis; atopic dermatitis; contact urticaria; irritant contact dermatitis; occupational hand eczema; prevention; socio-economic impact	SKIN-DISEASE; CONTACT-DERMATITIS; RISK-FACTORS; ALLERGY; POPULATION; PROGNOSIS; WORKERS; NICKEL; DERMATOSES; PREVALENCE	Occupational hand eczema (OHE) is the most frequently recognized work-related disease in Denmark and the annual cost to society is high. Understanding of the epidemiology of OHE is essential to be able to give appropriate recommendations for its prevention. The study comprised 758 persons, 490 females and 268 males with recognized OHE in the period October 2001 to November 2002. Data were obtained prospectively from the National Board of Industrial Industry Registry and from a self-administered questionnaire (response rate, 82%). The most frequently recognized diagnosis was irritant contact dermatitis (ICD), mainly caused by wet occupations. The proportion of occupational ICD was equal for males and females, 59.7% and 63.1%, respectively. The estimated rates of OHE were high for bakers, hairdressers and dental surgery assistants, and a high proportion of apprentices were found among hairdressers. The prevalence of atopic dermatitis was low (16.4%) compared to previous studies among hand eczema patients. The prevalence of occupational allergic contact dermatitis in the study population was substantially higher among males than females, and the most frequent causes among males were allergy to chromium (leather exposure), rubber additives (gloves) and nickel due to exposure from work tools and metalworking industry.	30	103	2004	8	10.1111/j.0105-1873.2004.00423.x	Allergy; Dermatology
"Field exercise vs laboratory eucapnic voluntary hyperventilation to identify airway hyperresponsiveness in elite cold weather athletes. Study objective: For the 2002 Winter Olympic Games, athletes were required to submit objective evidence of asthma or exercise-induced bronchoconstriction (EIB) for approval to inhale a beta(2)-agonist. Eucapnic voluntary hyperventilation (EVH) was recommended as a laboratory challenge that would identify airway hyperresponsiveness (AHR) consistent with EIB. The objective was to compare the change in FEV1 provoked by EVH with that provoked by exercise in cold weather athletes. Design: Spirometry was measured before and for 15 min after challenges. The two challenges were performed in random order at least 24 h apart. Setting: EVH was performed in the laboratory at 19degreesC, and exercise took place in the field in the cold (2degreesC, 45% relative humidity). Participants: Thirty-eight athletes (25 female subjects; median age, 16 years). Interventions: For the EVH, athletes inhaled dry air containing 5% carbon dioxide for 6 min at a target ventilation equivalent to 30 times baseline FEV1. Exercise was performed by cross-country skiing, ice skating, or running for 6 to 8 min. Measurements and results: AHR consistent with EIB was defined as greater than or equal to10% fall in FEV1 from baseline after challenge. Eleven athletes were exercise positive (EX+) [FEV1 fall, 20.5 +/- 7.3%], and 17 athletes were EVH positive (FEV1 fall, 14.5 +/- 4.5%) [mean +/- SD]. Of 19 subjects with AHR, 58% were identified by exercise and 89% were identified by EVH. EVH identified 9 of 11 subjects who were EX+ and a further 8 subjects with potential for EIB. The average ventilation during EVH was 28 times FEV1. Conclusion: Performing EVH for 6 min in the laboratory had a greater chance of identifying AHR in these athletes compared with 6 to 8 min of field exercise in the cold. The EVH test will be useful to evaluate elite summer sports athletes whose widely different forms of exercise provide an ""equipment"" challenge to any laboratory.. airway hyperresponsiveness| dry air| exercise| exercise-induced bronchoconstriction| eucapnic volontary hyperpnea|working party standardization| european respiratory society| thermally-induced asthma| refractory period| bronchial responsiveness| induced bronchospasm| official statement| hypertonic saline| challenge| children."	MAR-2004	airway hyperresponsiveness| dry air| exercise| exercise-induced bronchoconstriction| eucapnic volontary hyperpnea|working party standardization| european respiratory society| thermally-induced asthma| refractory period| bronchial responsiveness| induced bronchospasm| official statement| hypertonic saline| challenge| children	Rundell, KW; Anderson, SD; Spiering, BA; Judelson, DA	Field exercise vs laboratory eucapnic voluntary hyperventilation to identify airway hyperresponsiveness in elite cold weather athletes		CHEST	airway hyperresponsiveness; dry air; exercise; exercise-induced bronchoconstriction; eucapnic volontary hyperpnea	WORKING PARTY STANDARDIZATION; EUROPEAN RESPIRATORY SOCIETY; THERMALLY-INDUCED ASTHMA; REFRACTORY PERIOD; BRONCHIAL RESPONSIVENESS; INDUCED BRONCHOSPASM; OFFICIAL STATEMENT; HYPERTONIC SALINE; CHALLENGE; CHILDREN	"Study objective: For the 2002 Winter Olympic Games, athletes were required to submit objective evidence of asthma or exercise-induced bronchoconstriction (EIB) for approval to inhale a beta(2)-agonist. Eucapnic voluntary hyperventilation (EVH) was recommended as a laboratory challenge that would identify airway hyperresponsiveness (AHR) consistent with EIB. The objective was to compare the change in FEV1 provoked by EVH with that provoked by exercise in cold weather athletes. Design: Spirometry was measured before and for 15 min after challenges. The two challenges were performed in random order at least 24 h apart. Setting: EVH was performed in the laboratory at 19degreesC, and exercise took place in the field in the cold (2degreesC, 45% relative humidity). Participants: Thirty-eight athletes (25 female subjects; median age, 16 years). Interventions: For the EVH, athletes inhaled dry air containing 5% carbon dioxide for 6 min at a target ventilation equivalent to 30 times baseline FEV1. Exercise was performed by cross-country skiing, ice skating, or running for 6 to 8 min. Measurements and results: AHR consistent with EIB was defined as greater than or equal to10% fall in FEV1 from baseline after challenge. Eleven athletes were exercise positive (EX+) [FEV1 fall, 20.5 +/- 7.3%], and 17 athletes were EVH positive (FEV1 fall, 14.5 +/- 4.5%) [mean +/- SD]. Of 19 subjects with AHR, 58% were identified by exercise and 89% were identified by EVH. EVH identified 9 of 11 subjects who were EX+ and a further 8 subjects with potential for EIB. The average ventilation during EVH was 28 times FEV1. Conclusion: Performing EVH for 6 min in the laboratory had a greater chance of identifying AHR in these athletes compared with 6 to 8 min of field exercise in the cold. The EVH test will be useful to evaluate elite summer sports athletes whose widely different forms of exercise provide an ""equipment"" challenge to any laboratory."	36	103	2004	7	10.1378/chest.125.3.909	General & Internal Medicine; Respiratory System
"Inflammatory mediators in allergic rhinitis. Allergic rhinitis (AR) is part of a systemic disease complex. There is a close relationship between AR and asthma, which has led to the ""one airway, one disease"" concept. Both conditions share common immunopathology and pathophysiology. In patients with AR, allergen-triggered early and late responses are mediated by a series of inflammatory cells. Within minutes of contact with allergen, IgE-sensitized mast cells degranulate, releasing both preformed and newly synthesized mediators. Immunologic processes in both nasal and bronchial tissue involve T(H)2 lymphocytes and eosinophils. Eosinophils are the predominant cell in the chronic inflammatory process characteristic of the late-phase allergic response. Eosinophils release an array of proinflammatory mediators, including cysteinyl leukotrienes, cationic proteins, eosinophil peroxidase, and major basic protein, and might serve as a major source of IL-3, IL-5, GM-CSF, and IL-13. Neuropeptides also appear to contribute to the pathophysiology of AR symptoms. Both AR and asthma exhibit marked day-night variation in symptom severity. Acknowledging both the chronobiology of AR and circadian rhythm-dependent attributes of antiallergy medications might enhance the beneficial effects of allergy therapies. (J Allergy Clin Immunol 2004; 114: S135-8.). allergic rhinitis| inflammation| inflammatory mediators| asthma| chronotherapy| chronobiology| unified airway|antigen challenge| nasal secretions| mast-cells| asthma| exposure| expression| eosinophils| immunology| histamine| airways."	2004	allergic rhinitis| inflammation| inflammatory mediators| asthma| chronotherapy| chronobiology| unified airway|antigen challenge| nasal secretions| mast-cells| asthma| exposure| expression| eosinophils| immunology| histamine| airways	Gelfand, EW	Inflammatory mediators in allergic rhinitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergic rhinitis; inflammation; inflammatory mediators; asthma; chronotherapy; chronobiology; unified airway	ANTIGEN CHALLENGE; NASAL SECRETIONS; MAST-CELLS; ASTHMA; EXPOSURE; EXPRESSION; EOSINOPHILS; IMMUNOLOGY; HISTAMINE; AIRWAYS	"Allergic rhinitis (AR) is part of a systemic disease complex. There is a close relationship between AR and asthma, which has led to the ""one airway, one disease"" concept. Both conditions share common immunopathology and pathophysiology. In patients with AR, allergen-triggered early and late responses are mediated by a series of inflammatory cells. Within minutes of contact with allergen, IgE-sensitized mast cells degranulate, releasing both preformed and newly synthesized mediators. Immunologic processes in both nasal and bronchial tissue involve T(H)2 lymphocytes and eosinophils. Eosinophils are the predominant cell in the chronic inflammatory process characteristic of the late-phase allergic response. Eosinophils release an array of proinflammatory mediators, including cysteinyl leukotrienes, cationic proteins, eosinophil peroxidase, and major basic protein, and might serve as a major source of IL-3, IL-5, GM-CSF, and IL-13. Neuropeptides also appear to contribute to the pathophysiology of AR symptoms. Both AR and asthma exhibit marked day-night variation in symptom severity. Acknowledging both the chronobiology of AR and circadian rhythm-dependent attributes of antiallergy medications might enhance the beneficial effects of allergy therapies. (J Allergy Clin Immunol 2004; 114: S135-8.)"	39	103	2004	4	10.1016/j.jaci.2004.08.043	Allergy; Immunology
Cigarette smoking among asthmatic adults presenting to 64 emergency departments. Study objectives: The emergency department (ED) is an important focal point for asthmatic individuals with uncontrolled illness. Anecdotally, many adults presenting to the ED with acute asthma are active cigarette smokers. The present study determined the prevalence of cigarette smoking among adults presenting to the ED with acute asthma and identified the factors associated with current smoking status. Design: A prospective cohort study conducted as part of the Multicenter Airway Research Collaboration. Patients: A structured interview was performed in 1,847 patients, ages 18 to 54 years, who presented to the ED with acute asthma. Setting: Sixty-four EDs in 21 US states and 4 Canadian provinces. Results: Thirty-five percent of the enrolled asthmatic patients were current smokers with a median of 10 pack-years (interduartile range, 4 to 20 pack-years), while 23% were former smokers, and 42% were never-smokers. Current smokers comprised 33% of asthmatic patients aged 18 to 29 years, 40% for ages 30 to 39 years, and 33% for ages 40 to 54 (p < 0.001). In a multivariate analysis, the factors independently associated with current smoking status (p < 0.05) were as follows: age 30 to 39 years; white race/ethnicity; non-high school graduate; lower household income; lack of private insurance; no recent inhaled steroid usage; and no history of systemic steroid usage. Although 50% of current smokers admitted that smoking worsens their asthma symptoms, only 4% stated that smoking was responsible for their current exacerbation. Conclusions: Although cigarette smoke is generally recognized as a respiratory irritant, cigarette smoking is common among adults presenting to the ED with acute asthma. The ED visit may provide an opportunity for patients to be targeted for smoking cessation efforts.. acute disease| asthma| emergency medicine| smoking|lung-function| allergic rhinitis| passive smoking| bronchial hyperresponsiveness| pulmonary-function| maternal smoking| children| symptoms| prevalence| exposure.	MAY-2003	acute disease| asthma| emergency medicine| smoking|lung-function| allergic rhinitis| passive smoking| bronchial hyperresponsiveness| pulmonary-function| maternal smoking| children| symptoms| prevalence| exposure	Silverman, RA; Boudreaux, ED; Woodruff, PG; Clark, S; Camargo, CA	Cigarette smoking among asthmatic adults presenting to 64 emergency departments		CHEST	acute disease; asthma; emergency medicine; smoking	LUNG-FUNCTION; ALLERGIC RHINITIS; PASSIVE SMOKING; BRONCHIAL HYPERRESPONSIVENESS; PULMONARY-FUNCTION; MATERNAL SMOKING; CHILDREN; SYMPTOMS; PREVALENCE; EXPOSURE	Study objectives: The emergency department (ED) is an important focal point for asthmatic individuals with uncontrolled illness. Anecdotally, many adults presenting to the ED with acute asthma are active cigarette smokers. The present study determined the prevalence of cigarette smoking among adults presenting to the ED with acute asthma and identified the factors associated with current smoking status. Design: A prospective cohort study conducted as part of the Multicenter Airway Research Collaboration. Patients: A structured interview was performed in 1,847 patients, ages 18 to 54 years, who presented to the ED with acute asthma. Setting: Sixty-four EDs in 21 US states and 4 Canadian provinces. Results: Thirty-five percent of the enrolled asthmatic patients were current smokers with a median of 10 pack-years (interduartile range, 4 to 20 pack-years), while 23% were former smokers, and 42% were never-smokers. Current smokers comprised 33% of asthmatic patients aged 18 to 29 years, 40% for ages 30 to 39 years, and 33% for ages 40 to 54 (p < 0.001). In a multivariate analysis, the factors independently associated with current smoking status (p < 0.05) were as follows: age 30 to 39 years; white race/ethnicity; non-high school graduate; lower household income; lack of private insurance; no recent inhaled steroid usage; and no history of systemic steroid usage. Although 50% of current smokers admitted that smoking worsens their asthma symptoms, only 4% stated that smoking was responsible for their current exacerbation. Conclusions: Although cigarette smoke is generally recognized as a respiratory irritant, cigarette smoking is common among adults presenting to the ED with acute asthma. The ED visit may provide an opportunity for patients to be targeted for smoking cessation efforts.	59	103	2003	8	10.1378/chest.123.5.1472	General & Internal Medicine; Respiratory System
Indoor dampness and molds and development of adult-onset asthma: A population-based incident case-control study. Previous cross-sectional and prevalent case-control studies have suggested increased risk of asthma in adults related to dampness problems and molds in homes. We conducted a population-based incident case-control study to assess the effects of indoor dampness problems and molds at work and at home on development of asthma in adults. We recruited systematically all new cases of asthma during a 2.5-year study period (1997-2000) and randomly selected controls from a source population consisting of adults 21-63 years old living in the Pirkanmaa Hospital district, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls, after we excluded 76 (7.5%) controls with a history of asthma. In logistic regression analysis adjusting for confounders, the risk of asthma was related to the presence of visible mold and/or mold odor in the workplace (odds ratio, 1.54; 95% confidence interval, 1.01-2.32) but not to water damage or damp stains alone. We estimated the fraction of asthma attributable to workplace mold exposure to be 35.1% (95% confidence interval, 1.0-56.9%) among the exposed. Present results provide new evidence of the relation between workplace exposure to indoor molds and adult-onset asthma.. asthma| case-control study| molds| occupational exposure| population-based|day-care-centers| respiratory symptoms| home dampness| health| children| exposure| inflammation| associations| buildings| disease.	MAY-2002	asthma| case-control study| molds| occupational exposure| population-based|day-care-centers| respiratory symptoms| home dampness| health| children| exposure| inflammation| associations| buildings| disease	Jaakkola, MS; Nordman, H; Piipari, R; Uitti, J; Laitinen, J; Karjalainen, A; Hahtola, P; Jaakkola, JJK	Indoor dampness and molds and development of adult-onset asthma: A population-based incident case-control study		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; case-control study; molds; occupational exposure; population-based	DAY-CARE-CENTERS; RESPIRATORY SYMPTOMS; HOME DAMPNESS; HEALTH; CHILDREN; EXPOSURE; INFLAMMATION; ASSOCIATIONS; BUILDINGS; DISEASE	Previous cross-sectional and prevalent case-control studies have suggested increased risk of asthma in adults related to dampness problems and molds in homes. We conducted a population-based incident case-control study to assess the effects of indoor dampness problems and molds at work and at home on development of asthma in adults. We recruited systematically all new cases of asthma during a 2.5-year study period (1997-2000) and randomly selected controls from a source population consisting of adults 21-63 years old living in the Pirkanmaa Hospital district, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls, after we excluded 76 (7.5%) controls with a history of asthma. In logistic regression analysis adjusting for confounders, the risk of asthma was related to the presence of visible mold and/or mold odor in the workplace (odds ratio, 1.54; 95% confidence interval, 1.01-2.32) but not to water damage or damp stains alone. We estimated the fraction of asthma attributable to workplace mold exposure to be 35.1% (95% confidence interval, 1.0-56.9%) among the exposed. Present results provide new evidence of the relation between workplace exposure to indoor molds and adult-onset asthma.	32	103	2002	5		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Carbon monoxide: Innovative anti-inflammatory properties of an age-old gas molecule. Observations of the effects of carbon monoxide (CO) on mammalian systems have been known for thousands of years. To be sure, CO is deadly under certain conditions and concentrations, but perhaps as the data presented here will make clear, it also possesses other diverse functional and immunomodulatory properties. This review, together with the other reviews in this issue, will detail that over the past three decades, fundamental functional role(s) for this gas molecule are beginning to emerge. This review outlines that at low concentrations, exogenously administered CO is a molecule involved in the regulation of the inflammatory response in a variety of disease models. CO has been shown to modulate such cellular functions as cytokine production, cell proliferation and apoptosis, protecting the lungs and hearts of rodents from such stressors as endotoxin, ischemia/reperfusion injury, cardiac xenograft rejection, and asthma. Although the mechanism by which this simple diatomic gas provides this protection remains obscure, the conclusions are the same: CO at low concentrations, concentrations that are well below those that would otherwise create toxic effects, is proving beneficial in models of acute injury. CO, akin to nitric oxide, is proving to be an extraordinary signaling molecule generated by the cell that is vital in the regulation of cellular homeostasis.. tumor-necrosis-factor| heme oxygenase-1 suppresses| oxidative stress| lung injury| exhaled air| provides protection| physiological importance| immunological response| activated macrophages| factor biosynthesis.	APR-2002	tumor-necrosis-factor| heme oxygenase-1 suppresses| oxidative stress| lung injury| exhaled air| provides protection| physiological importance| immunological response| activated macrophages| factor biosynthesis	Otterbein, LE	Carbon monoxide: Innovative anti-inflammatory properties of an age-old gas molecule		ANTIOXIDANTS & REDOX SIGNALING		TUMOR-NECROSIS-FACTOR; HEME OXYGENASE-1 SUPPRESSES; OXIDATIVE STRESS; LUNG INJURY; EXHALED AIR; PROVIDES PROTECTION; PHYSIOLOGICAL IMPORTANCE; IMMUNOLOGICAL RESPONSE; ACTIVATED MACROPHAGES; FACTOR BIOSYNTHESIS	Observations of the effects of carbon monoxide (CO) on mammalian systems have been known for thousands of years. To be sure, CO is deadly under certain conditions and concentrations, but perhaps as the data presented here will make clear, it also possesses other diverse functional and immunomodulatory properties. This review, together with the other reviews in this issue, will detail that over the past three decades, fundamental functional role(s) for this gas molecule are beginning to emerge. This review outlines that at low concentrations, exogenously administered CO is a molecule involved in the regulation of the inflammatory response in a variety of disease models. CO has been shown to modulate such cellular functions as cytokine production, cell proliferation and apoptosis, protecting the lungs and hearts of rodents from such stressors as endotoxin, ischemia/reperfusion injury, cardiac xenograft rejection, and asthma. Although the mechanism by which this simple diatomic gas provides this protection remains obscure, the conclusions are the same: CO at low concentrations, concentrations that are well below those that would otherwise create toxic effects, is proving beneficial in models of acute injury. CO, akin to nitric oxide, is proving to be an extraordinary signaling molecule generated by the cell that is vital in the regulation of cellular homeostasis.	89	103	2002	11	10.1089/152308602753666361	Biochemistry & Molecular Biology; Endocrinology & Metabolism
In vitro T-cell responses to beta-lactam drugs in immediate and nonimmediate allergic reactions. Background: beta -Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin. Methods: Fifty patients with a well-documented history of allergic reactions to beta -lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug. Twenty-eight healthy subjects with good tolerance to penicillins served as controls. LTT was performed in all subjects. Results: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions. The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group. The LTT specificity was 92.8%. Conclusions: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests. Interestingly, positive T-cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.. drug allergy| beta-lactams| lymphocyte transformation test| skin tests| t cells|lymphocyte-transformation test| penicillin allergy| cross-reactivity| good tolerance| cutaneous reactions| ige antibodies| modified self| antibiotics| hypersensitivity| amoxicillin.	JUL-2001	drug allergy| beta-lactams| lymphocyte transformation test| skin tests| t cells|lymphocyte-transformation test| penicillin allergy| cross-reactivity| good tolerance| cutaneous reactions| ige antibodies| modified self| antibiotics| hypersensitivity| amoxicillin	Luque, I; Leyva, L; Torres, MJ; Rosal, M; Mayorga, C; Segura, JM; Blanca, M; Juarez, C	In vitro T-cell responses to beta-lactam drugs in immediate and nonimmediate allergic reactions		ALLERGY	drug allergy; beta-lactams; lymphocyte transformation test; skin tests; T cells	LYMPHOCYTE-TRANSFORMATION TEST; PENICILLIN ALLERGY; CROSS-REACTIVITY; GOOD TOLERANCE; CUTANEOUS REACTIONS; IGE ANTIBODIES; MODIFIED SELF; ANTIBIOTICS; HYPERSENSITIVITY; AMOXICILLIN	Background: beta -Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin. Methods: Fifty patients with a well-documented history of allergic reactions to beta -lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug. Twenty-eight healthy subjects with good tolerance to penicillins served as controls. LTT was performed in all subjects. Results: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions. The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group. The LTT specificity was 92.8%. Conclusions: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests. Interestingly, positive T-cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.	49	103	2001	8	10.1034/j.1398-9995.2001.000115.x	Allergy; Immunology
The mammalian safety of Bacillus thuringiensis-based insecticides. United States Environmental Protection Agency between the years 1961 and 1995 registered 177 products containing viable Bacillus thuringiensis (Bt), Numerous laboratory studies have demonstrated that Bt and Bt products are noninfectious and are toxic to mammals only at a dose greater than or equal to 10(8) colony forming units (cfu) per mouse (a human equivalent based on the weight of >10(11) cfu), In contrast, as few as three vegetative cells of Bacillus anthracis can kill mice (a human equivalent of >10(3) cfu), There are only two literature reports of Bt infection in man between the year 1997 and the present, and all infected individuals had experienced either extensive burns or a blast injury, which predisposed them to infection. Two epidemiology studies conducted during large-scale aerial Bt serovar kurstaki spray campaigns reported no increased incidence of illness, Some recent papers have expressed concern about the production of Bacillus cereus enterotoxins by Bt isolates, Laboratory studies found no evidence of illness in rats and sheep fed Bt products, nor have epidemiology studies found increased incidence of diarrhea during Bt aerial spray campaigns, Increases in human antibody levels following exposure to Bt products have been reported but there was no increased incidence in asthma or other illness, Based on laboratory studies and field experience, Bt insecticides have an excellent safety record.. bacillus thuringiensis| mammalian safety| infection of animals and man| bacillus cereus enterotoxins| persistence of spores| clearance of spores|cereus| strains| mice| enterotoxin| israelensis| pesticides| responses| infection| toxicity.	JAN-2001	bacillus thuringiensis| mammalian safety| infection of animals and man| bacillus cereus enterotoxins| persistence of spores| clearance of spores|cereus| strains| mice| enterotoxin| israelensis| pesticides| responses| infection| toxicity	Siegel, JP	The mammalian safety of Bacillus thuringiensis-based insecticides		JOURNAL OF INVERTEBRATE PATHOLOGY	Bacillus thuringiensis; mammalian safety; infection of animals and man; Bacillus cereus enterotoxins; persistence of spores; clearance of spores	CEREUS; STRAINS; MICE; ENTEROTOXIN; ISRAELENSIS; PESTICIDES; RESPONSES; INFECTION; TOXICITY	United States Environmental Protection Agency between the years 1961 and 1995 registered 177 products containing viable Bacillus thuringiensis (Bt), Numerous laboratory studies have demonstrated that Bt and Bt products are noninfectious and are toxic to mammals only at a dose greater than or equal to 10(8) colony forming units (cfu) per mouse (a human equivalent based on the weight of >10(11) cfu), In contrast, as few as three vegetative cells of Bacillus anthracis can kill mice (a human equivalent of >10(3) cfu), There are only two literature reports of Bt infection in man between the year 1997 and the present, and all infected individuals had experienced either extensive burns or a blast injury, which predisposed them to infection. Two epidemiology studies conducted during large-scale aerial Bt serovar kurstaki spray campaigns reported no increased incidence of illness, Some recent papers have expressed concern about the production of Bacillus cereus enterotoxins by Bt isolates, Laboratory studies found no evidence of illness in rats and sheep fed Bt products, nor have epidemiology studies found increased incidence of diarrhea during Bt aerial spray campaigns, Increases in human antibody levels following exposure to Bt products have been reported but there was no increased incidence in asthma or other illness, Based on laboratory studies and field experience, Bt insecticides have an excellent safety record.	42	103	2001	9	10.1006/jipa.2000.5000	Zoology
Detection of house-dust-mite allergen in amniotic fluid and umbilical-cord blood. Mononuclear cells In umbilical-cord blood display allergen-specific reactivity, but how allergen exposure occurs In utero is unknown. We Investigated the presence of a common inhalant allergen (Der p 1), to which mothers are exposed throughout pregnancy, by ELISA in matched maternal blood and amniotic fluid samples at 16-17 weeks of gestation, and in matched maternal and umbilical-cord blood at term (greater than or equal to 37 weeks of gestation). Der p 1 was detectable In 24 of 43 amniotic fluid samples where It was also present In maternal blood, and in 15 of 24 cord-plasma samples at significantly higher concentrations than in the maternal plasma (p=0.022). The detection of Der p 1 In the amniotic fluid and the fetal circulation provides direct evidence of transamniotic and transplacental allergen exposure.. fetal.	DEC 2-2000	fetal	Holloway, JA; Warner, JO; Vance, GHS; Diaper, ND; Warner, JA; Jones, CA	Detection of house-dust-mite allergen in amniotic fluid and umbilical-cord blood		LANCET		FETAL	Mononuclear cells In umbilical-cord blood display allergen-specific reactivity, but how allergen exposure occurs In utero is unknown. We Investigated the presence of a common inhalant allergen (Der p 1), to which mothers are exposed throughout pregnancy, by ELISA in matched maternal blood and amniotic fluid samples at 16-17 weeks of gestation, and in matched maternal and umbilical-cord blood at term (greater than or equal to 37 weeks of gestation). Der p 1 was detectable In 24 of 43 amniotic fluid samples where It was also present In maternal blood, and in 15 of 24 cord-plasma samples at significantly higher concentrations than in the maternal plasma (p=0.022). The detection of Der p 1 In the amniotic fluid and the fetal circulation provides direct evidence of transamniotic and transplacental allergen exposure.	5	103	2000	3	10.1016/S0140-6736(00)03265-7	General & Internal Medicine
Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice. Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characterized the strain distribution patterns for the asthma-related phenotypes airway hyperresponsiveness (AHR), lung eosinophils, and ovalbumin (OVA)-specific serum immunoglobulin (Ig) E induced by allergen exposure protocols in A/J, AKR/J, BALB/cJ, C3H/HeJ, and C57BL/6J inbred strains and in (C3H/HeJ x A/J)F1 mice. Expression of AHR differed between strains and was sometimes discordant with lung eosinophils or serum IgE. Furthermore, we identified two distinct quantitative trait loci (QTL) for susceptibility to allergen-induced AHR, Abhr1 (allergen-induced bronchial hyperresponsiveness) (lod = 4.2) and Abhr2 (lod = 3.7), on chromosome 2 in backcross progeny from A/J and C3H/HeJ mice. In addition, a QTL on chromosome 7 was suggestive of linkage to this trait. These QTL differ from those we have previously found to control noninflammatory AHR in the same crosses. Elucidation of the genes underlying these QTL will facilitate the identification of biochemical pathways regulating AHR in animal models of asthma and may provide insights into the pathogenesis of human disease.. genome-wide search| transcription factor gata-3| bronchial hyperreactivity| underlying asthma| linkage analysis| murine model| mouse model| t-cells| expression| inflammation.	OCT-2000	genome-wide search| transcription factor gata-3| bronchial hyperreactivity| underlying asthma| linkage analysis| murine model| mouse model| t-cells| expression| inflammation	Ewart, SL; Kuperman, D; Schadt, E; Tankersley, C; Grupe, A; Shubitowski, DM; Peltz, G; Wills-Karp, M	Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		GENOME-WIDE SEARCH; TRANSCRIPTION FACTOR GATA-3; BRONCHIAL HYPERREACTIVITY; UNDERLYING ASTHMA; LINKAGE ANALYSIS; MURINE MODEL; MOUSE MODEL; T-CELLS; EXPRESSION; INFLAMMATION	Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characterized the strain distribution patterns for the asthma-related phenotypes airway hyperresponsiveness (AHR), lung eosinophils, and ovalbumin (OVA)-specific serum immunoglobulin (Ig) E induced by allergen exposure protocols in A/J, AKR/J, BALB/cJ, C3H/HeJ, and C57BL/6J inbred strains and in (C3H/HeJ x A/J)F1 mice. Expression of AHR differed between strains and was sometimes discordant with lung eosinophils or serum IgE. Furthermore, we identified two distinct quantitative trait loci (QTL) for susceptibility to allergen-induced AHR, Abhr1 (allergen-induced bronchial hyperresponsiveness) (lod = 4.2) and Abhr2 (lod = 3.7), on chromosome 2 in backcross progeny from A/J and C3H/HeJ mice. In addition, a QTL on chromosome 7 was suggestive of linkage to this trait. These QTL differ from those we have previously found to control noninflammatory AHR in the same crosses. Elucidation of the genes underlying these QTL will facilitate the identification of biochemical pathways regulating AHR in animal models of asthma and may provide insights into the pathogenesis of human disease.	42	103	2000	9		Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Outdoor allergens. Outdoor allergens are an important part of the exposures that lead to allergic disease. Understanding the role of outdoor allergens requires a knowledge of the nature of outdoor allergen-bearing particles, the distributions of their source, and the nature of the aerosols (particle types, sizes, dynamics of concentrations). Primary sources for outdoor allergens include vascular plants (pollen, fern spores, soy dust), and fungi (spores. hyphae). Nonvascular plants, algae, and arthropods contribute small numbers of allergen-bearing particles. Particles are released from sources into the air by wind, rain, mechanical disturbance, or active discharge mechanisms. Once airborne, they follow the physical laws that apply to all airborne particles. Although some outdoor allergens penetrate indoor spaces, exposure occurs mostly outdoors. Even short-term peak outdoor exposures can be important in eliciting acute symptoms. Monitoring of airborne biological particles is usually by particle impaction and microscopic examination. Centrally located monitoring stations give regional-scale measurements for aeroallergen levels. Evidence for the role of outdoor allergens in allergic rhinitis is strong and is rapidly increasing for a role in asthma. Pollen and fungal spore exposures have both been implicated in acute exacerbations of asthma, and sensitivity to some fungal spores predicts the existence of asthma. Synergism and/or antagonism probably occurs with other outdoor air particles and gases. Control involves avoidance of exposure (staying indoors, preventing entry of outdoor aerosols) as well as immunotherapy. which is effective for pollen but of limited effect for spores. Outdoor allergens have been the subject of only limited studies with respect to the epidemiology of asthma. Much remains to be studied with respect to prevalence patterns, exposure acid disease relationships, and control.. asthma| exposure| fungal spores| outdoor allergens| pollen| predictive models|ragweed-pollen determinants| emergency room visits| air-pollution| soybean-dust| grass-pollen| atmospheric aerosol| epidemic asthma| exposure| particles| symptoms.	AUG-2000	asthma| exposure| fungal spores| outdoor allergens| pollen| predictive models|ragweed-pollen determinants| emergency room visits| air-pollution| soybean-dust| grass-pollen| atmospheric aerosol| epidemic asthma| exposure| particles| symptoms	Burge, HA; Rogers, CA	Outdoor allergens		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; exposure; fungal spores; outdoor allergens; pollen; predictive models	RAGWEED-POLLEN DETERMINANTS; EMERGENCY ROOM VISITS; AIR-POLLUTION; SOYBEAN-DUST; GRASS-POLLEN; ATMOSPHERIC AEROSOL; EPIDEMIC ASTHMA; EXPOSURE; PARTICLES; SYMPTOMS	Outdoor allergens are an important part of the exposures that lead to allergic disease. Understanding the role of outdoor allergens requires a knowledge of the nature of outdoor allergen-bearing particles, the distributions of their source, and the nature of the aerosols (particle types, sizes, dynamics of concentrations). Primary sources for outdoor allergens include vascular plants (pollen, fern spores, soy dust), and fungi (spores. hyphae). Nonvascular plants, algae, and arthropods contribute small numbers of allergen-bearing particles. Particles are released from sources into the air by wind, rain, mechanical disturbance, or active discharge mechanisms. Once airborne, they follow the physical laws that apply to all airborne particles. Although some outdoor allergens penetrate indoor spaces, exposure occurs mostly outdoors. Even short-term peak outdoor exposures can be important in eliciting acute symptoms. Monitoring of airborne biological particles is usually by particle impaction and microscopic examination. Centrally located monitoring stations give regional-scale measurements for aeroallergen levels. Evidence for the role of outdoor allergens in allergic rhinitis is strong and is rapidly increasing for a role in asthma. Pollen and fungal spore exposures have both been implicated in acute exacerbations of asthma, and sensitivity to some fungal spores predicts the existence of asthma. Synergism and/or antagonism probably occurs with other outdoor air particles and gases. Control involves avoidance of exposure (staying indoors, preventing entry of outdoor aerosols) as well as immunotherapy. which is effective for pollen but of limited effect for spores. Outdoor allergens have been the subject of only limited studies with respect to the epidemiology of asthma. Much remains to be studied with respect to prevalence patterns, exposure acid disease relationships, and control.	85	103	2000	7	10.2307/3454401	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Characteristics, Perceived Side Effects and Benefits of Electronic Cigarette Use: A Worldwide Survey of More than 19,000 Consumers. Background: Electronic cigarette (EC) use has grown exponentially over the past few years. The purpose of this survey was to assess the characteristics and experiences of a large sample of EC users and examine the differences between those who partially and completely substituted smoking with EC use. Methods: A questionnaire was prepared, translated into 10 different languages and uploaded in an online survey tool. EC users were asked to participate irrespective of their current smoking status. Participants were divided according to their smoking status at the time of participation in two subgroups: former smokers and current smokers. Results: In total, 19,414 participants were included in the analysis, with 88 of them (0.5%) reported not being smokers at the time of EC use initiation. Complete substitution of smoking was reported by 81.0% of participants (former smokers) while current smokers had reduced smoking consumption from 20 to 4 cigarettes per day. They were using ECs for a median of 10 months. They initiated EC use with a median of 18 mg/mL nicotine-concentration liquids; 21.5% used higher than 20 mg/mL. Only 3.5% of participants were using 0-nicotine liquids at the time of the survey. Former smokers were highly dependent (Fagerstrom Test for Cigarette Dependence = 7) and were heavier smokers (21 cigarettes per day when smoking) compared to current smokers. The most important reasons for initiating EC use for both subgroups was to reduce the harm associated with smoking and to reduce exposure of family members to second-hand smoking. Most considered ECs as less harmful than tobacco cigarettes, while 11.0% considered them absolutely harmless. Side effects were reported by more than half of the participants (59.8%), with the most common being sore/dry mouth and throat; side effects were mild and in most cases were subsequently resolved (partially or completely). Participants experienced significant benefits in physical status and improvements in pre-existing disease conditions (including respiratory disease such as asthma and chronic obstructive lung disease). Being former smoker was independently associated with positive effects in health and improvements in disease conditions. Conclusions: The results of this worldwide survey of dedicated users indicate that ECs are mostly used to avoid the harm associated with smoking. They can be effective even in highly-dependent smokers and are used as long-term substitutes for smoking. High levels of nicotine are used at initiation; subsequently, users try to reduce nicotine consumption, with only a small minority using non-nicotine liquids. Side effects are minor and health benefits are substantial, especially for those who completely substitute smoking with EC use. Further population and interventional studies are warranted.. lectronic cigarette| smoking| tobacco| nicotine| harm reduction| public health|nicotine delivery| smoking-cessation| internet survey| vapor extract| safety.	APR-2014	lectronic cigarette| smoking| tobacco| nicotine| harm reduction| public health|nicotine delivery| smoking-cessation| internet survey| vapor extract| safety	Farsalinos, KE; Romagna, G; Tsiapras, D; Kyrzopoulos, S; Voudris, V	Characteristics, Perceived Side Effects and Benefits of Electronic Cigarette Use: A Worldwide Survey of More than 19,000 Consumers		INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH	lectronic cigarette; smoking; tobacco; nicotine; harm reduction; public health	NICOTINE DELIVERY; SMOKING-CESSATION; INTERNET SURVEY; VAPOR EXTRACT; SAFETY	Background: Electronic cigarette (EC) use has grown exponentially over the past few years. The purpose of this survey was to assess the characteristics and experiences of a large sample of EC users and examine the differences between those who partially and completely substituted smoking with EC use. Methods: A questionnaire was prepared, translated into 10 different languages and uploaded in an online survey tool. EC users were asked to participate irrespective of their current smoking status. Participants were divided according to their smoking status at the time of participation in two subgroups: former smokers and current smokers. Results: In total, 19,414 participants were included in the analysis, with 88 of them (0.5%) reported not being smokers at the time of EC use initiation. Complete substitution of smoking was reported by 81.0% of participants (former smokers) while current smokers had reduced smoking consumption from 20 to 4 cigarettes per day. They were using ECs for a median of 10 months. They initiated EC use with a median of 18 mg/mL nicotine-concentration liquids; 21.5% used higher than 20 mg/mL. Only 3.5% of participants were using 0-nicotine liquids at the time of the survey. Former smokers were highly dependent (Fagerstrom Test for Cigarette Dependence = 7) and were heavier smokers (21 cigarettes per day when smoking) compared to current smokers. The most important reasons for initiating EC use for both subgroups was to reduce the harm associated with smoking and to reduce exposure of family members to second-hand smoking. Most considered ECs as less harmful than tobacco cigarettes, while 11.0% considered them absolutely harmless. Side effects were reported by more than half of the participants (59.8%), with the most common being sore/dry mouth and throat; side effects were mild and in most cases were subsequently resolved (partially or completely). Participants experienced significant benefits in physical status and improvements in pre-existing disease conditions (including respiratory disease such as asthma and chronic obstructive lung disease). Being former smoker was independently associated with positive effects in health and improvements in disease conditions. Conclusions: The results of this worldwide survey of dedicated users indicate that ECs are mostly used to avoid the harm associated with smoking. They can be effective even in highly-dependent smokers and are used as long-term substitutes for smoking. High levels of nicotine are used at initiation; subsequently, users try to reduce nicotine consumption, with only a small minority using non-nicotine liquids. Side effects are minor and health benefits are substantial, especially for those who completely substitute smoking with EC use. Further population and interventional studies are warranted.	25	102	2014	18	10.3390/ijerph110404356	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Symptom variability in patients with severe COPD: a pan-European cross-sectional study. In between exacerbations, chronic obstructive pulmonary disease (COPD) is usually regarded as a stable condition, but there is increasing recognition of variability in this state. This cross-sectional study assessed patients' perception of symptom variability. Participants were outpatients >45 yrs old with COPD, current or ex-smokers, forced expiratory volume in 1 s (FEV1) <50% predicted, FEV1/forced vital capacity <0.7 and no exacerbation leading to therapeutic intervention in the previous 3 months. Patients' perceptions of COPD symptoms and their impact on daily life activities were recorded. Alterations in therapy use in response to COPD worsening were also recorded. COPD symptoms were experienced by 2,258 (92.5%) out of 2,441 patients during the 7 days before interview. Breathlessness was the most common symptom (72.5%). Daily and/or weekly symptom variability was reported by 62.7% of symptomatic patients; the morning was the worst time of day. Factors associated with perception of variability of breathlessness included younger age, symptom severity and recruitment to the study by general practitioners. The perception of variability was significantly different between European countries or regions. Patient-perceived COPD symptoms vary over the day and the week, and impact on daily activities; morning being the worst time of day. The majority of patients appear not to adjust treatment when symptoms worsen.. breathlessness| chronic obstructive pulmonary disease| symptoms| symptom variability| treatment|obstructive pulmonary-disease| quality-of-life| air-flow obstruction| circadian variation| exacerbations| asthma| validation| tiotropium| impact.	FEB-2011	breathlessness| chronic obstructive pulmonary disease| symptoms| symptom variability| treatment|obstructive pulmonary-disease| quality-of-life| air-flow obstruction| circadian variation| exacerbations| asthma| validation| tiotropium| impact	Kessler, R; Partridge, MR; Miravitlles, M; Cazzola, M; Vogelmeier, C; Leynaud, D; Ostinelli, J	Symptom variability in patients with severe COPD: a pan-European cross-sectional study		EUROPEAN RESPIRATORY JOURNAL	Breathlessness; chronic obstructive pulmonary disease; symptoms; symptom variability; treatment	OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; AIR-FLOW OBSTRUCTION; CIRCADIAN VARIATION; EXACERBATIONS; ASTHMA; VALIDATION; TIOTROPIUM; IMPACT	In between exacerbations, chronic obstructive pulmonary disease (COPD) is usually regarded as a stable condition, but there is increasing recognition of variability in this state. This cross-sectional study assessed patients' perception of symptom variability. Participants were outpatients >45 yrs old with COPD, current or ex-smokers, forced expiratory volume in 1 s (FEV1) <50% predicted, FEV1/forced vital capacity <0.7 and no exacerbation leading to therapeutic intervention in the previous 3 months. Patients' perceptions of COPD symptoms and their impact on daily life activities were recorded. Alterations in therapy use in response to COPD worsening were also recorded. COPD symptoms were experienced by 2,258 (92.5%) out of 2,441 patients during the 7 days before interview. Breathlessness was the most common symptom (72.5%). Daily and/or weekly symptom variability was reported by 62.7% of symptomatic patients; the morning was the worst time of day. Factors associated with perception of variability of breathlessness included younger age, symptom severity and recruitment to the study by general practitioners. The perception of variability was significantly different between European countries or regions. Patient-perceived COPD symptoms vary over the day and the week, and impact on daily activities; morning being the worst time of day. The majority of patients appear not to adjust treatment when symptoms worsen.	30	102	2011	9	10.1183/09031936.00051110	Respiratory System
The relationship of respiratory and cardiovascular hospital admissions to the southern California wildfires of 2003. Objective: There is limited information on the public health impact of wildfires. The relationship of cardiorespiratory hospital admissions (n=40 856) to wildfire-related particulate matter (PM(2.5)) during catastrophic wildfires in southern California in October 2003 was evaluated. Methods: Zip code level PM(2.5) concentrations were estimated using spatial interpolations from measured PM(2.5), light extinction, meteorological conditions, and smoke information from MODIS satellite images at 250 m resolution. Generalised estimating equations for Poisson data were used to assess the relationship between daily admissions and PM(2.5), adjusted for weather, fungal spores (associated with asthma), weekend, zip code-level population and sociodemographics. Results: Associations of 2-day average PM(2.5) with respiratory admissions were stronger during than before or after the fires. Average increases of 70 mu g/m(3) PM(2.5) during heavy smoke conditions compared with PM(2.5) in the pre-wildfire period were associated with 34% increases in asthma admissions. The strongest wildfire-related PM(2.5) associations were for people ages 65 99 years (10.1% increase per 10 mu g/m(3) PM(2.5), 95% CI 3.0% to 17.8%) and ages 0-4 years (8.3%, 95% CI 2.2% to 14.9%) followed by ages 20-64 years (4.1%, 95% CI 20.5% to 9.0%). There were no PM(2.5)-asthma associations in children ages 5-18 years, although their admission rates significantly increased after the fires. Per 10 mg/m3 wildfire-related PM(2.5), acute bronchitis admissions across all ages increased by 9.6% (95% CI 1.8% to 17.9%), chronic obstructive pulmonary disease admissions for ages 20-64 years by 6.9% (95% CI 0.9% to 13.1%), and pneumonia admissions for ages 5-18 years by 6.4% (95% CI 21.0% to 14.2%). Acute bronchitis and pneumonia admissions also increased after the fires. There was limited evidence of a small impact of wildfire-related PM(2.5) on cardiovascular admissions. Conclusions: Wildfire-related PM(2.5) led to increased respiratory hospital admissions, especially asthma, suggesting that better preventive measures are required to reduce morbidity among vulnerable populations.. air-pollution| forest-fires| particulate matter| longitudinal data| acute asthma| exposure| smoke| mortality| quality| consequences.	MAR-2009	air-pollution| forest-fires| particulate matter| longitudinal data| acute asthma| exposure| smoke| mortality| quality| consequences	Delfino, RJ; Brummel, S; Wu, J; Stern, H; Ostro, B; Lipsett, M; Winer, A; Street, DH; Zhang, L; Tjoa, T; Gillen, DL	The relationship of respiratory and cardiovascular hospital admissions to the southern California wildfires of 2003		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		AIR-POLLUTION; FOREST-FIRES; PARTICULATE MATTER; LONGITUDINAL DATA; ACUTE ASTHMA; EXPOSURE; SMOKE; MORTALITY; QUALITY; CONSEQUENCES	Objective: There is limited information on the public health impact of wildfires. The relationship of cardiorespiratory hospital admissions (n=40 856) to wildfire-related particulate matter (PM(2.5)) during catastrophic wildfires in southern California in October 2003 was evaluated. Methods: Zip code level PM(2.5) concentrations were estimated using spatial interpolations from measured PM(2.5), light extinction, meteorological conditions, and smoke information from MODIS satellite images at 250 m resolution. Generalised estimating equations for Poisson data were used to assess the relationship between daily admissions and PM(2.5), adjusted for weather, fungal spores (associated with asthma), weekend, zip code-level population and sociodemographics. Results: Associations of 2-day average PM(2.5) with respiratory admissions were stronger during than before or after the fires. Average increases of 70 mu g/m(3) PM(2.5) during heavy smoke conditions compared with PM(2.5) in the pre-wildfire period were associated with 34% increases in asthma admissions. The strongest wildfire-related PM(2.5) associations were for people ages 65 99 years (10.1% increase per 10 mu g/m(3) PM(2.5), 95% CI 3.0% to 17.8%) and ages 0-4 years (8.3%, 95% CI 2.2% to 14.9%) followed by ages 20-64 years (4.1%, 95% CI 20.5% to 9.0%). There were no PM(2.5)-asthma associations in children ages 5-18 years, although their admission rates significantly increased after the fires. Per 10 mg/m3 wildfire-related PM(2.5), acute bronchitis admissions across all ages increased by 9.6% (95% CI 1.8% to 17.9%), chronic obstructive pulmonary disease admissions for ages 20-64 years by 6.9% (95% CI 0.9% to 13.1%), and pneumonia admissions for ages 5-18 years by 6.4% (95% CI 21.0% to 14.2%). Acute bronchitis and pneumonia admissions also increased after the fires. There was limited evidence of a small impact of wildfire-related PM(2.5) on cardiovascular admissions. Conclusions: Wildfire-related PM(2.5) led to increased respiratory hospital admissions, especially asthma, suggesting that better preventive measures are required to reduce morbidity among vulnerable populations.	40	102	2009	9	10.1136/oem.2008.041376	Public, Environmental & Occupational Health
Long-term decline in lung function, utilisation of care and quality of life in modified GOLD stage 1 COPD. Background: Little is known about the long-term outcomes of individuals with mild chronic obstructive pulmonary disease ( COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease ( GOLD). Methods: A population cohort of 6671 randomly selected adults without asthma was stratified into categories of modified GOLD-defined COPD (prebronchodilator spirometry). Further stratification was based on the presence or absence of respiratory symptoms. After 11 years, associations between baseline categories of COPD and decline in forced expiratory volume in 1 s (FEV(1)), respiratory care utilisation and quality of life as measured by the SF-36 questionnaire were examined after controlling for age, sex, smoking and educational status. Results: At baseline, modified GOLD criteria were met by 610 (9.1%) participants, 519 (85.1%) of whom had stage 1 COPD. At follow-up, individuals with symptomatic stage 1 COPD (n=224) had a faster decline in FEV1 (-9 ml/year (95% CI -13 to -5)), increased respiratory care utilisation (OR 1.6 (95% CI 1.0 to 2.6)) and a lower quality of life than asymptomatic subjects with normal lung function (n=3627, reference group). In contrast, individuals with asymptomatic stage 1 COPD (n=295) had no significant differences in FEV1 decline (-3 ml/year (95% CI -7 to +1)), respiratory care utilisation (OR 1.05 (95% CI 0.63 to 1.73)) or quality of life scores compared with the reference group. Conclusions: In population-based studies, respiratory symptoms are of major importance for predicting long-term clinical outcomes in subjects with COPD with mild obstruction. Population studies based on spirometry only may misestimate the prevalence of clinically relevant COPD.. obstructive pulmonary-disease| sf-36 health survey| nutrition-examination-survey| national-health| air-pollution| united-states| risk-factors| follow-up| prevalence| population.	SEP-2008	obstructive pulmonary-disease| sf-36 health survey| nutrition-examination-survey| national-health| air-pollution| united-states| risk-factors| follow-up| prevalence| population	Bridevaux, PO; Gerbase, MW; Probst-Hensch, NM; Schindler, C; Gaspoz, JM; Rochat, T	Long-term decline in lung function, utilisation of care and quality of life in modified GOLD stage 1 COPD		THORAX		OBSTRUCTIVE PULMONARY-DISEASE; SF-36 HEALTH SURVEY; NUTRITION-EXAMINATION-SURVEY; NATIONAL-HEALTH; AIR-POLLUTION; UNITED-STATES; RISK-FACTORS; FOLLOW-UP; PREVALENCE; POPULATION	Background: Little is known about the long-term outcomes of individuals with mild chronic obstructive pulmonary disease ( COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease ( GOLD). Methods: A population cohort of 6671 randomly selected adults without asthma was stratified into categories of modified GOLD-defined COPD (prebronchodilator spirometry). Further stratification was based on the presence or absence of respiratory symptoms. After 11 years, associations between baseline categories of COPD and decline in forced expiratory volume in 1 s (FEV(1)), respiratory care utilisation and quality of life as measured by the SF-36 questionnaire were examined after controlling for age, sex, smoking and educational status. Results: At baseline, modified GOLD criteria were met by 610 (9.1%) participants, 519 (85.1%) of whom had stage 1 COPD. At follow-up, individuals with symptomatic stage 1 COPD (n=224) had a faster decline in FEV1 (-9 ml/year (95% CI -13 to -5)), increased respiratory care utilisation (OR 1.6 (95% CI 1.0 to 2.6)) and a lower quality of life than asymptomatic subjects with normal lung function (n=3627, reference group). In contrast, individuals with asymptomatic stage 1 COPD (n=295) had no significant differences in FEV1 decline (-3 ml/year (95% CI -7 to +1)), respiratory care utilisation (OR 1.05 (95% CI 0.63 to 1.73)) or quality of life scores compared with the reference group. Conclusions: In population-based studies, respiratory symptoms are of major importance for predicting long-term clinical outcomes in subjects with COPD with mild obstruction. Population studies based on spirometry only may misestimate the prevalence of clinically relevant COPD.	35	102	2008	7	10.1136/thx.2007.093724	Respiratory System
Public health and economic impact of dampness and mold. The public health risk and economic impact of dampness and mold exposures was assessed using current asthma as a health endpoint. Individual risk of current asthma from exposure to dampness and mold in homes from W.J. Fisk, Q. Lei-Gomez & M.J. Mendell [(2007) Indoor Air 17, 226-235], and asthma risks calculated from additional studies that reported the prevalence of dampness and mold in homes were used to estimate the proportion of US current asthma cases that are attributable to dampness and mold exposure at 21% (95% confidence internal 12-29%). An examination of the literature covering dampness and mold in schools, offices, and institutional buildings, which is summarized in the Appendix, suggests that risks from exposure in these buildings are similar to risks from exposures in homes. Of the 21.8 million people reported to have asthma in the USA, approximately 4.6 (2.7-6.3) million cases are estimated to be attributable to dampness and mold exposure in the home. Estimates of the national cost of asthma from two prior studies were updated to 2004 and used to estimate the economic impact of dampness and mold exposures. By applying the attributable fraction to the updated national annual cost of asthma, the national annual cost of asthma that is attributable to dampness and mold exposure in the home is estimated to be $3.5 billion ($2.1-4.8 billion). Analysis indicates that exposure to dampness and mold in buildings poses significant public health and economic risks in the USA. These findings are compatible with public policies and programs that help control moisture and mold in buildings.. public| health| economic| impact| dampness| mold|building-related symptoms| adolescent school-children| respiratory symptoms| office workers| risk-factors| floor dust| airway inflammation| asthma prevalence| systemic symptoms| exposure.	JUN-2007	public| health| economic| impact| dampness| mold|building-related symptoms| adolescent school-children| respiratory symptoms| office workers| risk-factors| floor dust| airway inflammation| asthma prevalence| systemic symptoms| exposure	Mudarri, D; Fisk, WJ	Public health and economic impact of dampness and mold		INDOOR AIR	public; health; economic; impact; dampness; mold	BUILDING-RELATED SYMPTOMS; ADOLESCENT SCHOOL-CHILDREN; RESPIRATORY SYMPTOMS; OFFICE WORKERS; RISK-FACTORS; FLOOR DUST; AIRWAY INFLAMMATION; ASTHMA PREVALENCE; SYSTEMIC SYMPTOMS; EXPOSURE	The public health risk and economic impact of dampness and mold exposures was assessed using current asthma as a health endpoint. Individual risk of current asthma from exposure to dampness and mold in homes from W.J. Fisk, Q. Lei-Gomez & M.J. Mendell [(2007) Indoor Air 17, 226-235], and asthma risks calculated from additional studies that reported the prevalence of dampness and mold in homes were used to estimate the proportion of US current asthma cases that are attributable to dampness and mold exposure at 21% (95% confidence internal 12-29%). An examination of the literature covering dampness and mold in schools, offices, and institutional buildings, which is summarized in the Appendix, suggests that risks from exposure in these buildings are similar to risks from exposures in homes. Of the 21.8 million people reported to have asthma in the USA, approximately 4.6 (2.7-6.3) million cases are estimated to be attributable to dampness and mold exposure in the home. Estimates of the national cost of asthma from two prior studies were updated to 2004 and used to estimate the economic impact of dampness and mold exposures. By applying the attributable fraction to the updated national annual cost of asthma, the national annual cost of asthma that is attributable to dampness and mold exposure in the home is estimated to be $3.5 billion ($2.1-4.8 billion). Analysis indicates that exposure to dampness and mold in buildings poses significant public health and economic risks in the USA. These findings are compatible with public policies and programs that help control moisture and mold in buildings.	46	102	2007	10	10.1111/j.1600-0668.2007.00474.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Proteome changes in Arabidopsis thaliana roots upon exposure to Cd2+. Cadmium is a major environmental pollutant that enters human food via accumulation in crop plants. Responses of plants to cadmium exposure-which directly influence accumulation rates-are not well understood. In general, little is known about stress-elicited changes in plants at the proteome level. Alterations in the root proteome of hydroponically grown Arabidopsis thaliana plants treated with 10 mu M Cd2+ for 24 h are reported here. These conditions trigger the synthesis of phytochelatins (PCs), glutathione-derived metal-binding peptides, shown here as PC2 accumulation. Two-dimensional gel electrophoresis using different pH gradients in the first dimension detected on average similar to 1100 spots per gel type. Forty-one spots indicated significant changes in protein abundance upon Cd2+ treatment. Seventeen proteins found in 25 spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Selected results were independently confirmed by western analysis and selective enrichment of a protein family (glutathione S-transferases) through affinity chromatography. Most of the identified proteins belong to four different classes: metabolic enzymes such as ATP sulphurylase, glycine hydroxymethyltransferase, and trehalose-6-phosphate phosphatase; glutathione S-transferases; latex allergen-like proteins; and unknown proteins. These results represent a basis for reverse genetics studies to better understand plant responses to toxic metal exposure and to the generation of internal sinks for reduced sulphur.. cadmium| heavy metal accumulation| heavy metal tolerance| maldi-tof-ms| phytochelatins| proteomics|glutathione s-transferases| polyacrylamide-gels| membrane proteome| cadmium response| plant-responses| fission yeast| proteins| stress| metals| accumulation.	DEC-2006	cadmium| heavy metal accumulation| heavy metal tolerance| maldi-tof-ms| phytochelatins| proteomics|glutathione s-transferases| polyacrylamide-gels| membrane proteome| cadmium response| plant-responses| fission yeast| proteins| stress| metals| accumulation	Roth, U; von Roepenack-Lahaye, E; Clemens, S	Proteome changes in Arabidopsis thaliana roots upon exposure to Cd2+		JOURNAL OF EXPERIMENTAL BOTANY	cadmium; heavy metal accumulation; heavy metal tolerance; MALDI-TOF-MS; phytochelatins; proteomics	GLUTATHIONE S-TRANSFERASES; POLYACRYLAMIDE-GELS; MEMBRANE PROTEOME; CADMIUM RESPONSE; PLANT-RESPONSES; FISSION YEAST; PROTEINS; STRESS; METALS; ACCUMULATION	Cadmium is a major environmental pollutant that enters human food via accumulation in crop plants. Responses of plants to cadmium exposure-which directly influence accumulation rates-are not well understood. In general, little is known about stress-elicited changes in plants at the proteome level. Alterations in the root proteome of hydroponically grown Arabidopsis thaliana plants treated with 10 mu M Cd2+ for 24 h are reported here. These conditions trigger the synthesis of phytochelatins (PCs), glutathione-derived metal-binding peptides, shown here as PC2 accumulation. Two-dimensional gel electrophoresis using different pH gradients in the first dimension detected on average similar to 1100 spots per gel type. Forty-one spots indicated significant changes in protein abundance upon Cd2+ treatment. Seventeen proteins found in 25 spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Selected results were independently confirmed by western analysis and selective enrichment of a protein family (glutathione S-transferases) through affinity chromatography. Most of the identified proteins belong to four different classes: metabolic enzymes such as ATP sulphurylase, glycine hydroxymethyltransferase, and trehalose-6-phosphate phosphatase; glutathione S-transferases; latex allergen-like proteins; and unknown proteins. These results represent a basis for reverse genetics studies to better understand plant responses to toxic metal exposure and to the generation of internal sinks for reduced sulphur.	50	102	2006	11	10.1093/jxb/erl170	Plant Sciences
Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma. The pharmacokinetic and pharmacodynamic effects of inhaled corticosterolds (ICS) have shaped the efficacy and safety of these agents in the treatment of asthma. Important pharmacokinetic and pharmacodynamic characteristics that can enhance the efficacy of ICS include small particle size, high glucocorticoid-receptor-binding affinity, long pulmonary residence time and lipid conjugation. These characteristics can increase or prolong the anti-inflammatory effects of an ICS. Important pharmacokinetic characteristics that can enhance the safety of ICS include on-site activation in the lung, low oropharyngeal exposure, negligible oral bioavailability, high protein-binding and rapid systemic clearance. The degree of oropharyngeal exposure is relevant to local side-effects, such as oropharyngeal candidiasis, dysphonia and coughing. Pharmacokinetic properties that influence the degree of systemic exposure are relevant to the pharmacodynamic effect of ICS-induced hypothalamic-pituitary-adrenal axis suppression and cortisol suppression, an indicator of potential long-term systemic side-effects, such as reduced growth velocity and bone density, fractures, and skin bruising and thinning. Therefore, significant differences in the pharmacokinetic and pharmacodynamic characteristics of the currently available inhaled corticosteroids warrant careful consideration when used in clinical practice as they may result in differences in efficacy and local and systemic safety profiles.. ciclesonide| clinical relevance| cortisol| lipid conjugation| on-site activation| side-effects|metered-dose inhaler| adrenal axis function| high lung deposition| dry powder inhaler| mometasone furoate| fluticasone propionate| persistent asthma| beclomethasone dipropionate| intranasal corticosteroids| oropharyngeal deposition.	NOV-2006	ciclesonide| clinical relevance| cortisol| lipid conjugation| on-site activation| side-effects|metered-dose inhaler| adrenal axis function| high lung deposition| dry powder inhaler| mometasone furoate| fluticasone propionate| persistent asthma| beclomethasone dipropionate| intranasal corticosteroids| oropharyngeal deposition	Derendorf, H; Nave, R; Drollmann, A; Cerasoli, F; Wurst, W	Relevance of pharmacokinetics and pharmacodynamics of inhaled corticosteroids to asthma		EUROPEAN RESPIRATORY JOURNAL	ciclesonide; clinical relevance; cortisol; lipid conjugation; on-site activation; side-effects	METERED-DOSE INHALER; ADRENAL AXIS FUNCTION; HIGH LUNG DEPOSITION; DRY POWDER INHALER; MOMETASONE FUROATE; FLUTICASONE PROPIONATE; PERSISTENT ASTHMA; BECLOMETHASONE DIPROPIONATE; INTRANASAL CORTICOSTEROIDS; OROPHARYNGEAL DEPOSITION	The pharmacokinetic and pharmacodynamic effects of inhaled corticosterolds (ICS) have shaped the efficacy and safety of these agents in the treatment of asthma. Important pharmacokinetic and pharmacodynamic characteristics that can enhance the efficacy of ICS include small particle size, high glucocorticoid-receptor-binding affinity, long pulmonary residence time and lipid conjugation. These characteristics can increase or prolong the anti-inflammatory effects of an ICS. Important pharmacokinetic characteristics that can enhance the safety of ICS include on-site activation in the lung, low oropharyngeal exposure, negligible oral bioavailability, high protein-binding and rapid systemic clearance. The degree of oropharyngeal exposure is relevant to local side-effects, such as oropharyngeal candidiasis, dysphonia and coughing. Pharmacokinetic properties that influence the degree of systemic exposure are relevant to the pharmacodynamic effect of ICS-induced hypothalamic-pituitary-adrenal axis suppression and cortisol suppression, an indicator of potential long-term systemic side-effects, such as reduced growth velocity and bone density, fractures, and skin bruising and thinning. Therefore, significant differences in the pharmacokinetic and pharmacodynamic characteristics of the currently available inhaled corticosteroids warrant careful consideration when used in clinical practice as they may result in differences in efficacy and local and systemic safety profiles.	88	102	2006	9	10.1183/09031936.00074905	Respiratory System
"Daily time spent indoors in German homes - Baseline data for the assessment of indoor exposure of German occupants. Comprehensive time-activity studies, for use as a basis for estimates of personal exposure, are not readily available in Germany. This analysis of time spent indoors at home is based on data from ""Dampness and mould in homes"" (2000/ 2001) - a study of about 12,000 persons living in 5530 randomly selected apartments and houses in Germany. The results show the mean times per day people in Germany spend in their homes, classified by gender, age group, building location, city size, region, building type, owner-occupier status, number of people at home, smoking and ventilation habits, moisture emission and ill health factors such as asthma, allergy and number of acute respiratory infections per year. The overall mean time spent at home, 15.7 h per, is in accordance with results from US-American (15.6 h/day) and Canadian (15.8h/day) human activity surveys carried out in the nineties, as well as being consistent with the German Environmental Survey (1990/92) and a small German study in 1987. (c) 2005 Elsevier GmbH. All rights reserved.. time patterns| time spent at home| german homes| exposure estimation|activity-patterns."	2005	time patterns| time spent at home| german homes| exposure estimation|activity-patterns	Brasche, S; Bischof, W	Daily time spent indoors in German homes - Baseline data for the assessment of indoor exposure of German occupants		INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH	time patterns; time spent at home; German homes; exposure estimation	ACTIVITY-PATTERNS	"Comprehensive time-activity studies, for use as a basis for estimates of personal exposure, are not readily available in Germany. This analysis of time spent indoors at home is based on data from ""Dampness and mould in homes"" (2000/ 2001) - a study of about 12,000 persons living in 5530 randomly selected apartments and houses in Germany. The results show the mean times per day people in Germany spend in their homes, classified by gender, age group, building location, city size, region, building type, owner-occupier status, number of people at home, smoking and ventilation habits, moisture emission and ill health factors such as asthma, allergy and number of acute respiratory infections per year. The overall mean time spent at home, 15.7 h per, is in accordance with results from US-American (15.6 h/day) and Canadian (15.8h/day) human activity surveys carried out in the nineties, as well as being consistent with the German Environmental Survey (1990/92) and a small German study in 1987. (c) 2005 Elsevier GmbH. All rights reserved."	9	102	2005	7	10.1016/j.ijheh.2005.03.003	Public, Environmental & Occupational Health; Infectious Diseases
Socioeconomic status and asthma prevalence in young adults - The European Community Respiratory Health Survey. The authors assessed the association between asthma prevalence and socioeconomic status at both the individual and center levels simultaneously .by using data from 32 centers in 15 countries. Included were 10,971 subjects aged 20-44 years selected from the general population and interviewed in 1991-1992. Socioeconomic status at both the individual and aggregated levels was measured on the basis of occupation and educational level. Associations were assessed by using multilevel models adjusted for age, sex, body mass index, parental asthma, childhood respiratory infections, presence of immunoglobulin E to common allergens, rhinitis, smoking, and occupational exposure to irritants. Asthma prevalence was higher in lower socioeconomic groups, whether defined by educational level (odds ratio for finishing full-time studies-<16 vs. >19 years = 1.28, 95% confidence interval: 1.00, 1.64) or social class (odds ratio for semiskilled and unskilled manual workers vs. professional/managerial = 1.51, 95% confidence interval: 1.20, 1.90), regardless of atopic status. The relation was consistent between centers. Irrespective of individual socioeconomic status, subjects living in areas in which educational levels were lower had a higher risk of asthma (p < 0.05). This center-level association partially explained geographic differences in asthma prevalence, but considerable heterogeneity still remained. The authors concluded that community influences of living in a low-educational area are associated with asthma, independently of subjects' own educational level and social class.. adult| asthma| education| prevalence| social class|diagnosed asthma| admission rates| air-pollution| risk-factors| social-class| symptoms| epidemiology| children| area| deprivation.	JUL 15-2004	adult| asthma| education| prevalence| social class|diagnosed asthma| admission rates| air-pollution| risk-factors| social-class| symptoms| epidemiology| children| area| deprivation	Basagana, X; Sunyer, J; Kogevinas, M; Zock, JP; Duran-Tauleria, E; Jarvis, D; Burney, P; Anto, JM	Socioeconomic status and asthma prevalence in young adults - The European Community Respiratory Health Survey		AMERICAN JOURNAL OF EPIDEMIOLOGY	adult; asthma; education; prevalence; social class	DIAGNOSED ASTHMA; ADMISSION RATES; AIR-POLLUTION; RISK-FACTORS; SOCIAL-CLASS; SYMPTOMS; EPIDEMIOLOGY; CHILDREN; AREA; DEPRIVATION	The authors assessed the association between asthma prevalence and socioeconomic status at both the individual and center levels simultaneously .by using data from 32 centers in 15 countries. Included were 10,971 subjects aged 20-44 years selected from the general population and interviewed in 1991-1992. Socioeconomic status at both the individual and aggregated levels was measured on the basis of occupation and educational level. Associations were assessed by using multilevel models adjusted for age, sex, body mass index, parental asthma, childhood respiratory infections, presence of immunoglobulin E to common allergens, rhinitis, smoking, and occupational exposure to irritants. Asthma prevalence was higher in lower socioeconomic groups, whether defined by educational level (odds ratio for finishing full-time studies-<16 vs. >19 years = 1.28, 95% confidence interval: 1.00, 1.64) or social class (odds ratio for semiskilled and unskilled manual workers vs. professional/managerial = 1.51, 95% confidence interval: 1.20, 1.90), regardless of atopic status. The relation was consistent between centers. Irrespective of individual socioeconomic status, subjects living in areas in which educational levels were lower had a higher risk of asthma (p < 0.05). This center-level association partially explained geographic differences in asthma prevalence, but considerable heterogeneity still remained. The authors concluded that community influences of living in a low-educational area are associated with asthma, independently of subjects' own educational level and social class.	52	102	2004	11	10.1093/aje/kwh186	Public, Environmental & Occupational Health
Effects of intestinal microflora and the environment on the development of asthma and allergy. The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.. intestinal microflora| environment| asthma and allergy|placebo-controlled trial| neonatal gut flora| atopic disease| parental smoking| early-childhood| infectious-diseases| bcg vaccination| early exposure| house-dust| school-age.	FEB-2004	intestinal microflora| environment| asthma and allergy|placebo-controlled trial| neonatal gut flora| atopic disease| parental smoking| early-childhood| infectious-diseases| bcg vaccination| early exposure| house-dust| school-age	Bjorksten, B	Effects of intestinal microflora and the environment on the development of asthma and allergy		SPRINGER SEMINARS IN IMMUNOPATHOLOGY	intestinal microflora; environment; asthma and allergy	PLACEBO-CONTROLLED TRIAL; NEONATAL GUT FLORA; ATOPIC DISEASE; PARENTAL SMOKING; EARLY-CHILDHOOD; INFECTIOUS-DISEASES; BCG VACCINATION; EARLY EXPOSURE; HOUSE-DUST; SCHOOL-AGE	The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.	77	102	2004	14	10.1007/s00281-003-0142-2	Immunology; Pathology
A novel rice PR10 protein, RSOsPR10, specifically induced in roots by biotic and abiotic stresses, possibly via the jasmonic acid signaling pathway. Plant roots have important roles not only in absorption of water and nutrients, but also in stress tolerance such as desiccation, salt, and low temperature. We have investigated stress-response proteins from rice roots using 2-dimensional polyacrylamide-gel electrophoresis and found a rice protein, RO-292, which was induced specifically in roots when 2-week-old rice seedlings were subjected to salt and drought stress. The full-length RO-292 cDNA was cloned, and was determined to encode a protein of 160 amino acid residues (16.9 kDa, pI 4.74). The deduced amino acid sequence showed high similarity to known rice PR10 proteins, OSPR10a/PBZ1 and OsPR10b. RO-292 mRNA accumulated rapidly upon drought, NaCl, jasmonic acid and probenazole, but not by exposure to low temperature or by abscisic acid and salicylic acid. The RO-292 gene was also up-regulated by infection with rice blast fungus. Interestingly, induction was observed almost exclusively in roots, thus we named the gene RSOsPR10 (root specific rice PR10). The present results indicate that RSOsPR10 is a novel rice PR10 protein, which is rapidly induced in roots by salt, drought stresses and blast fungus infection possibly through activation of the jasmonic acid signaling pathway, but not the abscisic acid and salicylic acid signaling pathway.. fungal infection| jasmonic acid| oryza sativa| pathogenesis-related (pr) protein| root specific| stress response|pathogenesis-related proteins| birch pollen allergen| pisum-sativum l| disease resistance| abscisic-acid| ribonuclease-activity| sequence similarity| transgenic tobacco| gene-expression| cdna cloning.	2004	fungal infection| jasmonic acid| oryza sativa| pathogenesis-related (pr) protein| root specific| stress response|pathogenesis-related proteins| birch pollen allergen| pisum-sativum l| disease resistance| abscisic-acid| ribonuclease-activity| sequence similarity| transgenic tobacco| gene-expression| cdna cloning	Hashimoto, M; Kisseleva, L; Sawa, S; Furukawa, T; Komatsu, S; Koshiba, T	A novel rice PR10 protein, RSOsPR10, specifically induced in roots by biotic and abiotic stresses, possibly via the jasmonic acid signaling pathway		PLANT AND CELL PHYSIOLOGY	fungal infection; jasmonic acid; Oryza sativa; pathogenesis-related (PR) protein; root specific; stress response	PATHOGENESIS-RELATED PROTEINS; BIRCH POLLEN ALLERGEN; PISUM-SATIVUM L; DISEASE RESISTANCE; ABSCISIC-ACID; RIBONUCLEASE-ACTIVITY; SEQUENCE SIMILARITY; TRANSGENIC TOBACCO; GENE-EXPRESSION; CDNA CLONING	Plant roots have important roles not only in absorption of water and nutrients, but also in stress tolerance such as desiccation, salt, and low temperature. We have investigated stress-response proteins from rice roots using 2-dimensional polyacrylamide-gel electrophoresis and found a rice protein, RO-292, which was induced specifically in roots when 2-week-old rice seedlings were subjected to salt and drought stress. The full-length RO-292 cDNA was cloned, and was determined to encode a protein of 160 amino acid residues (16.9 kDa, pI 4.74). The deduced amino acid sequence showed high similarity to known rice PR10 proteins, OSPR10a/PBZ1 and OsPR10b. RO-292 mRNA accumulated rapidly upon drought, NaCl, jasmonic acid and probenazole, but not by exposure to low temperature or by abscisic acid and salicylic acid. The RO-292 gene was also up-regulated by infection with rice blast fungus. Interestingly, induction was observed almost exclusively in roots, thus we named the gene RSOsPR10 (root specific rice PR10). The present results indicate that RSOsPR10 is a novel rice PR10 protein, which is rapidly induced in roots by salt, drought stresses and blast fungus infection possibly through activation of the jasmonic acid signaling pathway, but not the abscisic acid and salicylic acid signaling pathway.	51	102	2004	10	10.1093/pcp/pch063	Plant Sciences; Cell Biology
From allergen structure to new forms of allergen-specific immunotherapy. During the past decade, genetic information for most of the common allergens has been obtained. Using these genetic blueprints it has become possible to reconstruct, by recombinant DNA technology, almost complete repertoires of the relevant allergens and their epitopes. Recombinant allergens with the allergenic features of naturally occurring allergens have promoted allergy research and form the basis of new multiallergen tests for refined allergy diagnosis. Allergen derivatives with reduced allergenic activity have also been produced by recombinant DNA technology to increase safety and specificity of allergen-specific immunotherapy. These derivatives can be engineered to contain relevant T cell epitopes and to maintain those sequence motifs which are required for inducing protective antibody responses and therefore hold great promise for improving allergen-specific immunotherapy.. birch pollen allergen| dust mite allergen| t-cell epitope| cross-reactive allergen| skin prick test| bet-v-i| engineered hypoallergenic derivatives| aspergillus-fumigatus allergens| quantitative ige inhibition| site-directed mutagenesis.	DEC-2002	birch pollen allergen| dust mite allergen| t-cell epitope| cross-reactive allergen| skin prick test| bet-v-i| engineered hypoallergenic derivatives| aspergillus-fumigatus allergens| quantitative ige inhibition| site-directed mutagenesis	Valenta, R; Kraft, D	From allergen structure to new forms of allergen-specific immunotherapy		CURRENT OPINION IN IMMUNOLOGY		BIRCH POLLEN ALLERGEN; DUST MITE ALLERGEN; T-CELL EPITOPE; CROSS-REACTIVE ALLERGEN; SKIN PRICK TEST; BET-V-I; ENGINEERED HYPOALLERGENIC DERIVATIVES; ASPERGILLUS-FUMIGATUS ALLERGENS; QUANTITATIVE IGE INHIBITION; SITE-DIRECTED MUTAGENESIS	During the past decade, genetic information for most of the common allergens has been obtained. Using these genetic blueprints it has become possible to reconstruct, by recombinant DNA technology, almost complete repertoires of the relevant allergens and their epitopes. Recombinant allergens with the allergenic features of naturally occurring allergens have promoted allergy research and form the basis of new multiallergen tests for refined allergy diagnosis. Allergen derivatives with reduced allergenic activity have also been produced by recombinant DNA technology to increase safety and specificity of allergen-specific immunotherapy. These derivatives can be engineered to contain relevant T cell epitopes and to maintain those sequence motifs which are required for inducing protective antibody responses and therefore hold great promise for improving allergen-specific immunotherapy.	138	102	2002	10	10.1016/S0952-7915(02)00402-8	Immunology
Low prevalence of atopy in young Danish farmers and farming students born and raised on a farm. Background Recent studies have shown that in several countries atopic sensitization to common allergens (common atopy) and atopic symptoms are markedly less prevalent in children living on a farm, compared with non-farm children living in the same rural areas. Living conditions on farms may, however, vary largely between different countries. It is also not yet known whether the 'protective' effect of a farm environment can also be found in adults. Materials and methods Common atopy and respiratory health were assessed by skin prick tests (SPT), questionnaire and measurement of bronchial hyper-responsiveness (BHR) in the Sund Stald (SUS) study, a cohort study on respiratory health in Danish farming students and conscripts from the same rural areas as controls. Results of SPT were confirmed by IgE serology in all SPT+ subjects and a subset of SPT- subjects. Prevalences of common atopy, respiratory symptoms and bronchial hyper- responsiveness were compared for farmers and controls, and for those who had or had not lived on a farm in early childhood. Results In multiple logistic regression analyses adjusting for ever smoking and a familial history of allergy, both being a farmer (ORs 0.62-0.75) and having had a farm childhood (ORs 0.55-0.75) appeared to contribute independently to a lower risk of sensitization to common allergens as assessed by SPT and IgE serology. A farm childhood was also inversely associated with high total IgE (OR 0.68), presence of respiratory symptoms (ORs 0.69-0.79) and BHR (OR 0.61) in these analyses. Direction and strength of the association between being a farmer and respiratory symptoms or BHR varied widely (ORs 0.69-1.28). Conclusions The 'anti-atopy' protective effect of a farm childhood could be confirmed in Danish farming students: prevalences of positive SPT, specific and total IgE, allergic symptoms and BHR were lower in those being born or raised on a farm. Past exposure to the farm environment in early childhood may therefore also contribute to a lower risk of atopic sensitization and disease at a later age.. atopy| denmark| farm childhood| farming| ige| skin prick tests| young farmers|hay-fever| allergic sensitization| respiratory symptoms| storage mites| asthma| exposure| children| dust| risk| population.	FEB-2002	atopy| denmark| farm childhood| farming| ige| skin prick tests| young farmers|hay-fever| allergic sensitization| respiratory symptoms| storage mites| asthma| exposure| children| dust| risk| population	Portengen, L; Sigsgaard, T; Omland, O; Hjort, C; Heederik, D; Doekes, G	Low prevalence of atopy in young Danish farmers and farming students born and raised on a farm		CLINICAL AND EXPERIMENTAL ALLERGY	atopy; Denmark; farm childhood; farming; IgE; skin prick tests; young farmers	HAY-FEVER; ALLERGIC SENSITIZATION; RESPIRATORY SYMPTOMS; STORAGE MITES; ASTHMA; EXPOSURE; CHILDREN; DUST; RISK; POPULATION	Background Recent studies have shown that in several countries atopic sensitization to common allergens (common atopy) and atopic symptoms are markedly less prevalent in children living on a farm, compared with non-farm children living in the same rural areas. Living conditions on farms may, however, vary largely between different countries. It is also not yet known whether the 'protective' effect of a farm environment can also be found in adults. Materials and methods Common atopy and respiratory health were assessed by skin prick tests (SPT), questionnaire and measurement of bronchial hyper-responsiveness (BHR) in the Sund Stald (SUS) study, a cohort study on respiratory health in Danish farming students and conscripts from the same rural areas as controls. Results of SPT were confirmed by IgE serology in all SPT+ subjects and a subset of SPT- subjects. Prevalences of common atopy, respiratory symptoms and bronchial hyper- responsiveness were compared for farmers and controls, and for those who had or had not lived on a farm in early childhood. Results In multiple logistic regression analyses adjusting for ever smoking and a familial history of allergy, both being a farmer (ORs 0.62-0.75) and having had a farm childhood (ORs 0.55-0.75) appeared to contribute independently to a lower risk of sensitization to common allergens as assessed by SPT and IgE serology. A farm childhood was also inversely associated with high total IgE (OR 0.68), presence of respiratory symptoms (ORs 0.69-0.79) and BHR (OR 0.61) in these analyses. Direction and strength of the association between being a farmer and respiratory symptoms or BHR varied widely (ORs 0.69-1.28). Conclusions The 'anti-atopy' protective effect of a farm childhood could be confirmed in Danish farming students: prevalences of positive SPT, specific and total IgE, allergic symptoms and BHR were lower in those being born or raised on a farm. Past exposure to the farm environment in early childhood may therefore also contribute to a lower risk of atopic sensitization and disease at a later age.	28	102	2002	7	10.1046/j.1365-2222.2002.01310.x	Allergy; Immunology
The role of outdoor air pollution and climatic changes on the rising trends in respiratory allergy. Evidence suggests that allergic respiratory diseases such as hay fever and bronchial asthma have become more common world-wide in the last two decades, and the reasons for this increase are still largely unknown. A major responsible factor could be outdoor air pollution, derived from cars and other vehicles. Studies have demonstrated that urbanization and high levels of vehicle emissions and westernized lifestyle is correlated with the increasing frequency of pollen-induced respiratory allergy. People who live in urban areas tend to be more affected by pollen-induced respiratory allergy than those from of rural areas. Pollen allergy has been one of the most frequent models used to study the interrelationship between air pollution and respiratory allergic diseases. Pollen grains or plant-derived paucimicronic components carry allergens that can produce allergic symptoms. They may also interact with air pollution (particulate matter; ozone) in producing these effects. There is evidence that air pollutants may promote airway sensitization by modulating the allergenicity of airborne allergens. Furthermore, airway mucosal damage and impaired mucociliary clearance induced by air pollution may facilitate the access Of inhaled allergens to the cells of the immune system. In addition, vegetation reacts with air pollution and environmental conditions and influence the plant allergenicity. Several factors influence this interaction, including type of air pollutants, plant species, nutrient balance: climatic factors, degree of airway sensitization and hyperresponsiveness of exposed subjects.. air pollution| bronchial asthma| airway hyper-responsiveness| hay fever| pollinosis| respiratory allergy| urban pollution|diesel exhaust particles| pollen-related allergy| grass-pollen| asthmatic-children| particulate matter| ozone exposure| health| inflammation| mortality| airways.	JUL-2001	air pollution| bronchial asthma| airway hyper-responsiveness| hay fever| pollinosis| respiratory allergy| urban pollution|diesel exhaust particles| pollen-related allergy| grass-pollen| asthmatic-children| particulate matter| ozone exposure| health| inflammation| mortality| airways	D'Amato, G; Liccardi, G; D'Amato, M; Cazzola, M	The role of outdoor air pollution and climatic changes on the rising trends in respiratory allergy		RESPIRATORY MEDICINE	air pollution; bronchial asthma; airway hyper-responsiveness; hay fever; pollinosis; respiratory allergy; urban pollution	DIESEL EXHAUST PARTICLES; POLLEN-RELATED ALLERGY; GRASS-POLLEN; ASTHMATIC-CHILDREN; PARTICULATE MATTER; OZONE EXPOSURE; HEALTH; INFLAMMATION; MORTALITY; AIRWAYS	Evidence suggests that allergic respiratory diseases such as hay fever and bronchial asthma have become more common world-wide in the last two decades, and the reasons for this increase are still largely unknown. A major responsible factor could be outdoor air pollution, derived from cars and other vehicles. Studies have demonstrated that urbanization and high levels of vehicle emissions and westernized lifestyle is correlated with the increasing frequency of pollen-induced respiratory allergy. People who live in urban areas tend to be more affected by pollen-induced respiratory allergy than those from of rural areas. Pollen allergy has been one of the most frequent models used to study the interrelationship between air pollution and respiratory allergic diseases. Pollen grains or plant-derived paucimicronic components carry allergens that can produce allergic symptoms. They may also interact with air pollution (particulate matter; ozone) in producing these effects. There is evidence that air pollutants may promote airway sensitization by modulating the allergenicity of airborne allergens. Furthermore, airway mucosal damage and impaired mucociliary clearance induced by air pollution may facilitate the access Of inhaled allergens to the cells of the immune system. In addition, vegetation reacts with air pollution and environmental conditions and influence the plant allergenicity. Several factors influence this interaction, including type of air pollutants, plant species, nutrient balance: climatic factors, degree of airway sensitization and hyperresponsiveness of exposed subjects.	55	102	2001	6	10.1053/rmed.2001.1112	Cardiovascular System & Cardiology; Respiratory System
Do obese inner-city children with asthma have more symptoms than nonobese children with asthma?. Objective. To test whether obesity is associated with decreased peak expiratory flow rates (PEFR), increased asthma symptoms, and increased health service use. Design/Methods. Secondary analysis of data from a cross-sectional convenience sample. Setting. Emergency departments (EDs) and primary care clinics in 8 inner-city areas in 7 cities. Participants. One thousand three hundred twenty-two children aged 4 to 9 years with asthma. Measures. Obesity was defined as a body mass index (BMI, weight/height(2)) >95th percentile. Nonobese children were those with a BMI between the 5th and 95th percentile. Underweight children with a BMI <5th percentile were eliminated from the study. Demographic and anthropometric data were obtained during a baseline interview with the primary caretaker and the child. Symptoms, health service use data and measurements of PEFR were obtained by parental report during the baseline interview and at 3-month intervals by telephone interview over the following 9-month period. Results. Obese (n = 249) and nonobese (n = 1073) children did not differ in terms of age, gender, family income, passive smoke exposure, caretaker's mental health, and skin test reactivity to indoor allergens. Obese children were more often Latino (28% vs 17%) and, in the 3 months before the baseline interview, were more likely to have used oral steroids (30% vs 24%). There were no differences between groups in terms of baseline PEFR scores. During the 9 months after baseline assessment, the obese group had a higher mean number of days of wheeze per 2-week period (4.0 vs 3.4), and a greater proportion of obese individuals had unscheduled ED visits (39% vs 31%). There were no differences between the groups in terms of frequency of hospitalization, or in nocturnal awakening. Conclusions. In our sample of inner-city children with asthma, obese children used more medicine, wheezed more, and a greater proportion had unscheduled ED visits than the nonobese children.. asthma| obesity| children| peak expiratory flow| inner-city|body-mass index| united-states| adolescents| overweight| association| sample| growth| black.	DEC-2000	asthma| obesity| children| peak expiratory flow| inner-city|body-mass index| united-states| adolescents| overweight| association| sample| growth| black	Belamarich, PF; Luder, E; Kattan, M; Mitchell, H; Islam, S; Lynn, H; Crain, EF	Do obese inner-city children with asthma have more symptoms than nonobese children with asthma?		PEDIATRICS	asthma; obesity; children; peak expiratory flow; inner-city	BODY-MASS INDEX; UNITED-STATES; ADOLESCENTS; OVERWEIGHT; ASSOCIATION; SAMPLE; GROWTH; BLACK	Objective. To test whether obesity is associated with decreased peak expiratory flow rates (PEFR), increased asthma symptoms, and increased health service use. Design/Methods. Secondary analysis of data from a cross-sectional convenience sample. Setting. Emergency departments (EDs) and primary care clinics in 8 inner-city areas in 7 cities. Participants. One thousand three hundred twenty-two children aged 4 to 9 years with asthma. Measures. Obesity was defined as a body mass index (BMI, weight/height(2)) >95th percentile. Nonobese children were those with a BMI between the 5th and 95th percentile. Underweight children with a BMI <5th percentile were eliminated from the study. Demographic and anthropometric data were obtained during a baseline interview with the primary caretaker and the child. Symptoms, health service use data and measurements of PEFR were obtained by parental report during the baseline interview and at 3-month intervals by telephone interview over the following 9-month period. Results. Obese (n = 249) and nonobese (n = 1073) children did not differ in terms of age, gender, family income, passive smoke exposure, caretaker's mental health, and skin test reactivity to indoor allergens. Obese children were more often Latino (28% vs 17%) and, in the 3 months before the baseline interview, were more likely to have used oral steroids (30% vs 24%). There were no differences between groups in terms of baseline PEFR scores. During the 9 months after baseline assessment, the obese group had a higher mean number of days of wheeze per 2-week period (4.0 vs 3.4), and a greater proportion of obese individuals had unscheduled ED visits (39% vs 31%). There were no differences between the groups in terms of frequency of hospitalization, or in nocturnal awakening. Conclusions. In our sample of inner-city children with asthma, obese children used more medicine, wheezed more, and a greater proportion had unscheduled ED visits than the nonobese children.	24	102	2000	6	10.1542/peds.106.6.1436	Pediatrics
The effect of inhaled budesonide on symptoms, lung function, and cold air and methacholine responsiveness in 2-to 5-year-old asthmatic children. We hypothesized that measurement of lung function (LF) and bronchial hyperresponsiveness (BHR) could serve as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids in asthmatic children aged 2 to 5 yr. We studied 38 children (mean age: 53 mo; range: 35 to 71 mo) with moderately severe asthma in a single-center, randomized, double-blind, parallel-group, placebo-controlled study involving 8 wk of treatment. Budesonide (BUD) 400 mu g twice daily was administered via a pressurized metered-dose inhaler and metal spacer device. Symptom scores (SSc) and use of short-acting beta(2)-agonist were monitored with diary cards. LF in awake children was measured as the specific airway resistance (sRaw), using whole-body plethysmography; as resistance by the interrupter technique (Rint); and as resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique. Cold air challenge (CACh) and methacholine challenge (MCh) were used to assess BHR. Children in the BUD group experienced significantly fewer night- and daytime symptoms (p < 0.05) and more symptom-free days (p < 0.05), but not nights (p = 0.07), than children in the placebo group. Daytime (p < 0.05) but not nighttime (p = 0.09) use of rescue medication and asthma exacerbation rates (3.7 versus 9.3 exacerbations/yr) (p = 0.006) were both in favor of BUD. LF measured with the Rint technique, Rrs5, and Xrs5 were significantly improved by BUD. BHR as measured by CACh improved significantly with BUD, whereas no improvement was found on MCh. In conclusion, inhaled BUD at a total dose of 800 mu g daily significantly Improved SSc, asthma exacerbation rates, lung function, and BHR as assessed by CACh in asthmatic children aged 2 to 5 yr.. young-children| dry air| bronchial responsiveness| inhalation suspension| nebulized budesonide| persistent asthma| challenge| histamine| infants| hyperventilation.	OCT-2000	young-children| dry air| bronchial responsiveness| inhalation suspension| nebulized budesonide| persistent asthma| challenge| histamine| infants| hyperventilation	Nielsen, KG; Bisgaard, H	The effect of inhaled budesonide on symptoms, lung function, and cold air and methacholine responsiveness in 2-to 5-year-old asthmatic children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		YOUNG-CHILDREN; DRY AIR; BRONCHIAL RESPONSIVENESS; INHALATION SUSPENSION; NEBULIZED BUDESONIDE; PERSISTENT ASTHMA; CHALLENGE; HISTAMINE; INFANTS; HYPERVENTILATION	We hypothesized that measurement of lung function (LF) and bronchial hyperresponsiveness (BHR) could serve as supplemental tools in evaluating the efficacy of treatment with inhaled corticosteroids in asthmatic children aged 2 to 5 yr. We studied 38 children (mean age: 53 mo; range: 35 to 71 mo) with moderately severe asthma in a single-center, randomized, double-blind, parallel-group, placebo-controlled study involving 8 wk of treatment. Budesonide (BUD) 400 mu g twice daily was administered via a pressurized metered-dose inhaler and metal spacer device. Symptom scores (SSc) and use of short-acting beta(2)-agonist were monitored with diary cards. LF in awake children was measured as the specific airway resistance (sRaw), using whole-body plethysmography; as resistance by the interrupter technique (Rint); and as resistance and reactance at 5 Hz (Rrs5, Xrs5) by the impulse oscillation technique. Cold air challenge (CACh) and methacholine challenge (MCh) were used to assess BHR. Children in the BUD group experienced significantly fewer night- and daytime symptoms (p < 0.05) and more symptom-free days (p < 0.05), but not nights (p = 0.07), than children in the placebo group. Daytime (p < 0.05) but not nighttime (p = 0.09) use of rescue medication and asthma exacerbation rates (3.7 versus 9.3 exacerbations/yr) (p = 0.006) were both in favor of BUD. LF measured with the Rint technique, Rrs5, and Xrs5 were significantly improved by BUD. BHR as measured by CACh improved significantly with BUD, whereas no improvement was found on MCh. In conclusion, inhaled BUD at a total dose of 800 mu g daily significantly Improved SSc, asthma exacerbation rates, lung function, and BHR as assessed by CACh in asthmatic children aged 2 to 5 yr.	33	102	2000	7		General & Internal Medicine; Respiratory System
Early nutrition and the development of immune function in the neonate. The present review will concentrate on the development of the gut-associated lymphoid tissue and the role of early nutrition in promoting immune function. The intestine is the largest immune organ in the body, and as such is the location for the majority of lymphocytes and other immune effector cells. The intestine is exposed to vast quantities of dietary and microbial antigens, and is the most common portal of entry for pathogens, some of which are potentially lethal. The development of normal immune function of the intestine is therefore vital for survival, and is dependent on appropriate antigen exposure and processing, and also an intact intestinal barrier. In early life innate mechanisms of defence are probably more important than active or adaptive mechanisms in responding to an infectious challenge, since the healthy neonate is immunologically naive (has not seen antigen) and has not acquired immunological memory. During this period maternal colostrum and milk can significantly augment resistance to enteric infections. The mechanisms of enhancing disease resistance are thought to be passive, involving a direct supply of anti-microbial factors, and active, by promoting the development of specific immune function. A tolerance response to dietary and non-invasive antigens is generally induced in the gut. However, it must also be able to mount an adequate immune response to ensure clearance of foreign antigens. It is now recognized that regulation of tolerance and active immune responses is critical to health, and failure to regulate these responses can lead to recurrent infections, inflammatory diseases and allergies. The education of the immune system in early life is thought to be critical in minimizing the occurrence of these immune-based disorders. During this phase of development maternal milk provides signals to the immune system that generate appropriate response and memory. One factor that has been proposed to contribute to the increase in the incidence of immune-based disorders, e.g. atopic diseases in Western countries, is thought to be the increased prevalence of formula-feeding.. intestine| immunity| neonate| colostrum|intestinal epithelial-cells| fimbriated escherichia-coli| blood group antigens| human-milk| t-cells| immunohistochemical analysis| mucosal surfaces| suckling pigs| expression| colostrum.	MAY-2000	intestine| immunity| neonate| colostrum|intestinal epithelial-cells| fimbriated escherichia-coli| blood group antigens| human-milk| t-cells| immunohistochemical analysis| mucosal surfaces| suckling pigs| expression| colostrum	Kelly, D; Coutts, AGP	Early nutrition and the development of immune function in the neonate		PROCEEDINGS OF THE NUTRITION SOCIETY	intestine; immunity; neonate; colostrum	INTESTINAL EPITHELIAL-CELLS; FIMBRIATED ESCHERICHIA-COLI; BLOOD GROUP ANTIGENS; HUMAN-MILK; T-CELLS; IMMUNOHISTOCHEMICAL ANALYSIS; MUCOSAL SURFACES; SUCKLING PIGS; EXPRESSION; COLOSTRUM	The present review will concentrate on the development of the gut-associated lymphoid tissue and the role of early nutrition in promoting immune function. The intestine is the largest immune organ in the body, and as such is the location for the majority of lymphocytes and other immune effector cells. The intestine is exposed to vast quantities of dietary and microbial antigens, and is the most common portal of entry for pathogens, some of which are potentially lethal. The development of normal immune function of the intestine is therefore vital for survival, and is dependent on appropriate antigen exposure and processing, and also an intact intestinal barrier. In early life innate mechanisms of defence are probably more important than active or adaptive mechanisms in responding to an infectious challenge, since the healthy neonate is immunologically naive (has not seen antigen) and has not acquired immunological memory. During this period maternal colostrum and milk can significantly augment resistance to enteric infections. The mechanisms of enhancing disease resistance are thought to be passive, involving a direct supply of anti-microbial factors, and active, by promoting the development of specific immune function. A tolerance response to dietary and non-invasive antigens is generally induced in the gut. However, it must also be able to mount an adequate immune response to ensure clearance of foreign antigens. It is now recognized that regulation of tolerance and active immune responses is critical to health, and failure to regulate these responses can lead to recurrent infections, inflammatory diseases and allergies. The education of the immune system in early life is thought to be critical in minimizing the occurrence of these immune-based disorders. During this phase of development maternal milk provides signals to the immune system that generate appropriate response and memory. One factor that has been proposed to contribute to the increase in the incidence of immune-based disorders, e.g. atopic diseases in Western countries, is thought to be the increased prevalence of formula-feeding.	58	102	2000	9	10.1017/S0029665100000197	Nutrition & Dietetics
Non-invasive markers of airway inflammation as predictors of oral steroid responsiveness in asthma. Background-Sputum eosinophil counts and exhaled nitric oxide (NO) levels are increased in asthma and both measurements fall in response to corticosteroids. Methods-Exhaled NO levels and sputum eosinophil counts were assessed as noninvasive markers of the response to an oral steroid in 37 patients (19 women) with stable chronic asthma (mean (SD) age 48.6 (12.2) years, asthma duration 25.9 (17.3) years, and baseline forced expiratory volume in one second (FEV1) 76.3 (21.9)% predicted). Spirometric tests, with reversibility to a beta agonist (2.5 mg nebulised salbutamol), and induced sputum (using nebulised 3% saline) were performed at recruitment and following treatment with 30 mg prednisolone/day for 14 days. Results-Baseline NO levels correlated with the percentage improvement in FEV, from baseline to the post-steroid, postbronchodilator value (r(s) = 0.47, p = 0.003), with an NO level of >10 ppb at baseline having a positive predictive value of 83% for an improvement in FEV, of greater than or equal to 15% (sensitivity 59%, specificity 90%). Sputum eosinophilia (greater than or equal to 4%) had a positive predictive value of 68% (sensitivity 54%, specificity 76%) for an increase in FEV1 of greater than or equal to 15%. A combination of sputum eosinophilia and increased NO levels resulted in a positive predictive value of 72% and a negative predictive value of 79% (sensitivity 76%, specificity 75%). Conclusion-Exhaled NO levels and sputum eosinophilia may be useful in predicting the response to a trial of oral steroid in asthma.. airway inflammation| nitric oxide| induced sputum eosinophilia| asthma| corticosteroids|nitric-oxide| exhaled air| sputum.	MAR-2000	airway inflammation| nitric oxide| induced sputum eosinophilia| asthma| corticosteroids|nitric-oxide| exhaled air| sputum	Little, SA; Chalmers, GW; MacLeod, KJ; McSharry, C; Thomson, NC	Non-invasive markers of airway inflammation as predictors of oral steroid responsiveness in asthma		THORAX	airway inflammation; nitric oxide; induced sputum eosinophilia; asthma; corticosteroids	NITRIC-OXIDE; EXHALED AIR; SPUTUM	Background-Sputum eosinophil counts and exhaled nitric oxide (NO) levels are increased in asthma and both measurements fall in response to corticosteroids. Methods-Exhaled NO levels and sputum eosinophil counts were assessed as noninvasive markers of the response to an oral steroid in 37 patients (19 women) with stable chronic asthma (mean (SD) age 48.6 (12.2) years, asthma duration 25.9 (17.3) years, and baseline forced expiratory volume in one second (FEV1) 76.3 (21.9)% predicted). Spirometric tests, with reversibility to a beta agonist (2.5 mg nebulised salbutamol), and induced sputum (using nebulised 3% saline) were performed at recruitment and following treatment with 30 mg prednisolone/day for 14 days. Results-Baseline NO levels correlated with the percentage improvement in FEV, from baseline to the post-steroid, postbronchodilator value (r(s) = 0.47, p = 0.003), with an NO level of >10 ppb at baseline having a positive predictive value of 83% for an improvement in FEV, of greater than or equal to 15% (sensitivity 59%, specificity 90%). Sputum eosinophilia (greater than or equal to 4%) had a positive predictive value of 68% (sensitivity 54%, specificity 76%) for an increase in FEV1 of greater than or equal to 15%. A combination of sputum eosinophilia and increased NO levels resulted in a positive predictive value of 72% and a negative predictive value of 79% (sensitivity 76%, specificity 75%). Conclusion-Exhaled NO levels and sputum eosinophilia may be useful in predicting the response to a trial of oral steroid in asthma.	10	102	2000	3	10.1136/thorax.55.3.232	Respiratory System
Risk factors for irritable bowel syndrome: Role of analgesics and food sensitivities. OBJECTIVE: Symptoms of irritable bowel syndrome (IBS) are reported by 10% of the general population; however, evaluation of traditional risk factors has not provided any insight into the pathogenesis of this condition. The objective of this study was to identify additional risk factors for irritable bowel syndrome. METHODS: A valid self-report questionnaire that records the gastrointestinal (GI) symptoms required for a diagnosis of IBS, self-reported measures of potential risk factors, and a psychosomatic symptom checklist was mailed to an age- and gender-stratified random sample of Olmsted County, Minnesota residents aged 30-64 yr. A logistic regression model that adjusted for age, gender, and psychosomatic symptom score was used to identify factors significantly associated with IBS. RESULTS: A total of 643 (72%) of 892 eligible subjects returned the survey. IBS symptoms were reported by 12% of the respondents. IBS was significantly associated with use of analgesics (acetaminophen, aspirin, or nonaspirin nonsteroidal antiinflammatory drugs) for reasons other than IBS, reporting a food allergy or sensitivity, and ratings of somatic symptoms. No association was detected for age, gender, body mass index, smoking history, alcohol use, educational level, exposure to pets in the household, or water supply. Among subjects reporting the use of just one type of analgesic, IBS was associated with acetaminophen but not aspirin or nonaspirin nonsteroidal antiinflammatory drugs used alone. The odds of having IBS were higher among subjects reporting more reasons for taking analgesics and intolerance to a higher number of foods. CONCLUSIONS: IBS is significantly associated with analgesic use. However, this is confounded by other somatic pain complaints. IBS symptoms are associated with the reporting of many food allergies or sensitivities. The role of food-induced symptoms in IBS requires further investigation.. functional gastrointestinal disorders| epidemiology| population| prevalence| symptoms| dyspepsia| history.	JAN-2000	functional gastrointestinal disorders| epidemiology| population| prevalence| symptoms| dyspepsia| history	Locke, GR; Zinsmeister, AR; Talley, NJ; Fett, SL; Melton, LJ	Risk factors for irritable bowel syndrome: Role of analgesics and food sensitivities		AMERICAN JOURNAL OF GASTROENTEROLOGY		FUNCTIONAL GASTROINTESTINAL DISORDERS; EPIDEMIOLOGY; POPULATION; PREVALENCE; SYMPTOMS; DYSPEPSIA; HISTORY	OBJECTIVE: Symptoms of irritable bowel syndrome (IBS) are reported by 10% of the general population; however, evaluation of traditional risk factors has not provided any insight into the pathogenesis of this condition. The objective of this study was to identify additional risk factors for irritable bowel syndrome. METHODS: A valid self-report questionnaire that records the gastrointestinal (GI) symptoms required for a diagnosis of IBS, self-reported measures of potential risk factors, and a psychosomatic symptom checklist was mailed to an age- and gender-stratified random sample of Olmsted County, Minnesota residents aged 30-64 yr. A logistic regression model that adjusted for age, gender, and psychosomatic symptom score was used to identify factors significantly associated with IBS. RESULTS: A total of 643 (72%) of 892 eligible subjects returned the survey. IBS symptoms were reported by 12% of the respondents. IBS was significantly associated with use of analgesics (acetaminophen, aspirin, or nonaspirin nonsteroidal antiinflammatory drugs) for reasons other than IBS, reporting a food allergy or sensitivity, and ratings of somatic symptoms. No association was detected for age, gender, body mass index, smoking history, alcohol use, educational level, exposure to pets in the household, or water supply. Among subjects reporting the use of just one type of analgesic, IBS was associated with acetaminophen but not aspirin or nonaspirin nonsteroidal antiinflammatory drugs used alone. The odds of having IBS were higher among subjects reporting more reasons for taking analgesics and intolerance to a higher number of foods. CONCLUSIONS: IBS is significantly associated with analgesic use. However, this is confounded by other somatic pain complaints. IBS symptoms are associated with the reporting of many food allergies or sensitivities. The role of food-induced symptoms in IBS requires further investigation.	20	102	2000	9		Gastroenterology & Hepatology
Desert Dust Exposure Is Associated with Increased Risk of Asthma Hospitalization in Children. Rationale: Desert dust particles, including quartz, which causes inflammatory responses in the airway in animal studies, are transported to widespread regions around the globe. Epidemiologically, areas impacted by desert dust storms, such as communities in the Middle East and the Caribbean, seem to have higher incidences of asthma than might be expected. Objectives: We investigated the magnitude of association between airborne mineral dust concentration and hospitalization of children for asthma exacerbation by using Light Detection And Ranging (LIDAR) with a polarization analyzer for an exposure measurement, which can distinguish mineral dust particles from other particles. Methods: A case-crossover design was used. The exposure measurement was LIDAR's nonspherical extinction coefficient. The outcome measurement was hospitalization of children aged 1 to 15 years for asthma exacerbation in eight principal hospitals in Toyama, a local area in japan bordering the Japan Sea, during February to April, 2005 to 2009. Measurements and Main Results: During the study period, there were 620 admissions for asthma exacerbation, and 6 days with a heavy dust event (daily mineral dust concentration > 0.1 mg/m(3)). Conditional logistic regression showed a statistically significant association between asthma hospitalization and a heavy dust event. The crude odds ratio (OR) of the heavy dust event for hospitalization on the day was 1.88 (95% confidence interval [Cl], 1.04-3.41; P = 0.037), and the OR of heavy dust event during the previous week was 1.83 (95% Cl, 1.31-2.56; P = 0.00043). The OR adjusted by other air pollutant levels, pollen, and meteorological factors was 1.71 (95% Cl, 1.18-2.48; P = 0.0050). Conclusions: Heavy dust events are associated with an increased risk of hospitalizations for asthma.. asian dust| kosa| mineral dust| african dust| quartz|asian sand dust| bidirectional case-crossover| optical-particle counter| peak expiratory flow| respiratory symptoms| particulate matter| lidar measurements| human health| trade winds| aerosol.	DEC 15-2010	asian dust| kosa| mineral dust| african dust| quartz|asian sand dust| bidirectional case-crossover| optical-particle counter| peak expiratory flow| respiratory symptoms| particulate matter| lidar measurements| human health| trade winds| aerosol	Kanatani, KT; Ito, I; Al-Delaimy, WK; Adachi, Y; Mathews, WC; Ramsdell, JW	Desert Dust Exposure Is Associated with Increased Risk of Asthma Hospitalization in Children		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	Asian dust; Kosa; mineral dust; African dust; quartz	ASIAN SAND DUST; BIDIRECTIONAL CASE-CROSSOVER; OPTICAL-PARTICLE COUNTER; PEAK EXPIRATORY FLOW; RESPIRATORY SYMPTOMS; PARTICULATE MATTER; LIDAR MEASUREMENTS; HUMAN HEALTH; TRADE WINDS; AEROSOL	Rationale: Desert dust particles, including quartz, which causes inflammatory responses in the airway in animal studies, are transported to widespread regions around the globe. Epidemiologically, areas impacted by desert dust storms, such as communities in the Middle East and the Caribbean, seem to have higher incidences of asthma than might be expected. Objectives: We investigated the magnitude of association between airborne mineral dust concentration and hospitalization of children for asthma exacerbation by using Light Detection And Ranging (LIDAR) with a polarization analyzer for an exposure measurement, which can distinguish mineral dust particles from other particles. Methods: A case-crossover design was used. The exposure measurement was LIDAR's nonspherical extinction coefficient. The outcome measurement was hospitalization of children aged 1 to 15 years for asthma exacerbation in eight principal hospitals in Toyama, a local area in japan bordering the Japan Sea, during February to April, 2005 to 2009. Measurements and Main Results: During the study period, there were 620 admissions for asthma exacerbation, and 6 days with a heavy dust event (daily mineral dust concentration > 0.1 mg/m(3)). Conditional logistic regression showed a statistically significant association between asthma hospitalization and a heavy dust event. The crude odds ratio (OR) of the heavy dust event for hospitalization on the day was 1.88 (95% confidence interval [Cl], 1.04-3.41; P = 0.037), and the OR of heavy dust event during the previous week was 1.83 (95% Cl, 1.31-2.56; P = 0.00043). The OR adjusted by other air pollutant levels, pollen, and meteorological factors was 1.71 (95% Cl, 1.18-2.48; P = 0.0050). Conclusions: Heavy dust events are associated with an increased risk of hospitalizations for asthma.	46	101	2010	7	10.1164/rccm.201002-0296OC	General & Internal Medicine; Respiratory System
House dust mite allergens in asthma and allergy. IgE antibodies in house dust mite (HDM) allergy follow a predictable pattern. Half are directed against two dominant allergens and the remainder largely against four midpotency allergens. This hierarchical pattern is not changed by the titre of the IgE response or severity of disease. The structures of these allergens are known and they can be produced as authentic recombinant allergens. There is also evidence that the allergenicity is augmented by the biological activity of the key allergens, validating them as targets for vaccination. Collectively, these developments should facilitate the development of new diagnostics, improve immunotherapy and allow vaccination with defined reagents. Highly purified recombinant polypeptides representing the important mite allergens are now available so that informative and reproducible experiments can be performed with mite allergens in place of poorly defined and variable extracts.. blomia-tropicalis allergens| ige cross-reactivity| dermatophagoides-pteronyssinus| major allergen| cysteine proteases| structural biology| crystal-structure| escherichia-coli| p 2| recombinant.	JUL-2010	blomia-tropicalis allergens| ige cross-reactivity| dermatophagoides-pteronyssinus| major allergen| cysteine proteases| structural biology| crystal-structure| escherichia-coli| p 2| recombinant	Thomas, WR; Hales, BJ; Smith, WA	House dust mite allergens in asthma and allergy		TRENDS IN MOLECULAR MEDICINE		BLOMIA-TROPICALIS ALLERGENS; IGE CROSS-REACTIVITY; DERMATOPHAGOIDES-PTERONYSSINUS; MAJOR ALLERGEN; CYSTEINE PROTEASES; STRUCTURAL BIOLOGY; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; P 2; RECOMBINANT	IgE antibodies in house dust mite (HDM) allergy follow a predictable pattern. Half are directed against two dominant allergens and the remainder largely against four midpotency allergens. This hierarchical pattern is not changed by the titre of the IgE response or severity of disease. The structures of these allergens are known and they can be produced as authentic recombinant allergens. There is also evidence that the allergenicity is augmented by the biological activity of the key allergens, validating them as targets for vaccination. Collectively, these developments should facilitate the development of new diagnostics, improve immunotherapy and allow vaccination with defined reagents. Highly purified recombinant polypeptides representing the important mite allergens are now available so that informative and reproducible experiments can be performed with mite allergens in place of poorly defined and variable extracts.	68	101	2010	8	10.1016/j.molmed.2010.04.008	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Particulate Air Pollution and Acute Cardiorespiratory Hospital Admissions and Mortality Among the Elderly. Background: It is known that particulate air pollution affects cardiorespiratory health; however, it is unclear which particle size fractions and sources of particles are responsible for the health effects. Methods: Daily levels of nucleation (<0.03 mu m), Aitken (0.03-0.1 mu m), accumulation (0.1-0.29 mu m), and coarse mode (2.5-10 mu m) particles, particles with diameter <2.5 mu m (PM(2.5)), and gaseous pollutants were measured at central outdoor measurement sites in Helsinki, Finland between 1998 and 2004. We determined the associations of particles with daily cardiorespiratory mortality and acute hospital admissions among the elderly (>= 65 years). For the analyses we used Poisson generalized additive models and for the source apportionment of PM(2.5) we used the EPA positive matrix factorization method. Results: There was a suggestion of an association of hospital admissions for arrhythmia with Aitken mode particles and PM,., from traffic. Otherwise few associations were observed between various sizes and types of particles and either cardiovascular admissions or mortality. In contrast, most particle fractions had positive associations with admissions for pneumonia and asthma-chronic obstructive pulmonary disease (COPD). The strongest and most consistent associations were found for accumulation mode particles (3.1%; 95% confidence interval = 0.43-5.8 for pneumonia over the 5-day mean, and 3.8%; 1.3-6.3 for asthma-COPD at lag 0, for an interquartile increase in particles). We also found a positive association of respiratory mortality mainly with accumulation mode particles (5.1%; 1.2-9.0 at lag 0). Conclusions: All particle fractions including Aitken, accumulation, and coarse mode had especially adverse respiratory health effects among the elderly. Overall associations were stronger for respiratory than for cardiovascular outcomes.. emergency-department visits| source apportionment| ultrafine particles| european cities| fine particles| ambient pm2.5| urban air| associations| health| helsinki.	JAN-2009	emergency-department visits| source apportionment| ultrafine particles| european cities| fine particles| ambient pm2.5| urban air| associations| health| helsinki	Halonen, JI; Lanki, T; Yli-Tuomi, T; Tiittanen, P; Kulmala, M; Pekkanen, J	Particulate Air Pollution and Acute Cardiorespiratory Hospital Admissions and Mortality Among the Elderly		EPIDEMIOLOGY		EMERGENCY-DEPARTMENT VISITS; SOURCE APPORTIONMENT; ULTRAFINE PARTICLES; EUROPEAN CITIES; FINE PARTICLES; AMBIENT PM2.5; URBAN AIR; ASSOCIATIONS; HEALTH; HELSINKI	Background: It is known that particulate air pollution affects cardiorespiratory health; however, it is unclear which particle size fractions and sources of particles are responsible for the health effects. Methods: Daily levels of nucleation (<0.03 mu m), Aitken (0.03-0.1 mu m), accumulation (0.1-0.29 mu m), and coarse mode (2.5-10 mu m) particles, particles with diameter <2.5 mu m (PM(2.5)), and gaseous pollutants were measured at central outdoor measurement sites in Helsinki, Finland between 1998 and 2004. We determined the associations of particles with daily cardiorespiratory mortality and acute hospital admissions among the elderly (>= 65 years). For the analyses we used Poisson generalized additive models and for the source apportionment of PM(2.5) we used the EPA positive matrix factorization method. Results: There was a suggestion of an association of hospital admissions for arrhythmia with Aitken mode particles and PM,., from traffic. Otherwise few associations were observed between various sizes and types of particles and either cardiovascular admissions or mortality. In contrast, most particle fractions had positive associations with admissions for pneumonia and asthma-chronic obstructive pulmonary disease (COPD). The strongest and most consistent associations were found for accumulation mode particles (3.1%; 95% confidence interval = 0.43-5.8 for pneumonia over the 5-day mean, and 3.8%; 1.3-6.3 for asthma-COPD at lag 0, for an interquartile increase in particles). We also found a positive association of respiratory mortality mainly with accumulation mode particles (5.1%; 1.2-9.0 at lag 0). Conclusions: All particle fractions including Aitken, accumulation, and coarse mode had especially adverse respiratory health effects among the elderly. Overall associations were stronger for respiratory than for cardiovascular outcomes.	42	101	2009	11	10.1097/EDE.0b013e31818c7237	Public, Environmental & Occupational Health
An Overview of 9/11 Experiences and Respiratory and Mental Health Conditions among World Trade Center Health Registry Enrollees. To date, health effects of exposure to the September 11, 2001 disaster in New York City have been studied in specific groups, but no studies have estimated its impact across the different exposed populations. This report provides an overview of the World Trade Center Health Registry (WTCHR) enrollees, their exposures, and their respiratory and mental health outcomes 2-3 years post-9/11. Results are extrapolated to the estimated universe of people eligible to enroll in the WTCHR to determine magnitude of impact. Building occupants, persons on the street or in transit in lower Manhattan on 9/11, local residents, rescue and recovery workers/volunteers, and area school children and staff were interviewed and enrolled in the WTCHR between September 2003 and November 2004. A total of 71,437 people enrolled in the WTCHR, for 17.4% coverage of the estimated eligible exposed population (nearly 410,000); 30% were recruited from lists, and 70% were self-identified. Many reported being in the dust cloud from the collapsing WTC Towers (51%), witnessing traumatic events (70%), or sustaining an injury (13%). After 9/11, 67% of adult enrollees reported new or worsening respiratory symptoms, 3% reported newly diagnosed asthma, 16% screened positive for probable posttraumatic stress disorder (PTSD), and 8% for serious psychological distress (SPD). Newly diagnosed asthma was most common among rescue and recovery workers who worked on the debris pile (4.1%). PTSD was higher among those who reported Hispanic ethnicity (30%), household income <$25,000 (31%), or being injured (35%). Using previously published estimates of the total number of exposed people per WTCHR eligibility criteria, we estimate between 3,800 and 12,600 adults experienced newly diagnosed asthma and 34,600-70,200 adults experienced PTSD following the attacks, suggesting extensive adverse health impacts beyond the immediate deaths and injuries from the acute event.. world trade center| asthma| respiratory symptoms| posttraumatic stress disorder| serious psychological distress| population estimates of wtc disaster health outcomes| world trade center health registry (wtchr)| environmental exposures| new york city| children| terrorism| wtc attacks| epidemiology| mental health|posttraumatic-stress-disorder| new-york-city| september-11 terrorist attacks| national comorbidity survey| center disaster site| st-helens eruptions| ptsd checklist| pulmonary-function| civilian version| police officers.	NOV-2008	world trade center| asthma| respiratory symptoms| posttraumatic stress disorder| serious psychological distress| population estimates of wtc disaster health outcomes| world trade center health registry (wtchr)| environmental exposures| new york city| children| terrorism| wtc attacks| epidemiology| mental health|posttraumatic-stress-disorder| new-york-city| september-11 terrorist attacks| national comorbidity survey| center disaster site| st-helens eruptions| ptsd checklist| pulmonary-function| civilian version| police officers	Farfel, M; DiGrande, L; Brackbill, R; Prann, A; Cone, J; Friedman, S; Walker, DJ; Pezeshki, G; Thomas, P; Galea, S; Williamson, D; Frieden, TR; Thorpe, L	An Overview of 9/11 Experiences and Respiratory and Mental Health Conditions among World Trade Center Health Registry Enrollees		JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE	World Trade Center; Asthma; Respiratory symptoms; Posttraumatic stress disorder; Serious psychological distress; Population estimates of WTC disaster health outcomes; World Trade Center Health Registry (WTCHR); Environmental exposures; New York City; Children; Terrorism; WTC attacks; Epidemiology; Mental health	POSTTRAUMATIC-STRESS-DISORDER; NEW-YORK-CITY; SEPTEMBER-11 TERRORIST ATTACKS; NATIONAL COMORBIDITY SURVEY; CENTER DISASTER SITE; ST-HELENS ERUPTIONS; PTSD CHECKLIST; PULMONARY-FUNCTION; CIVILIAN VERSION; POLICE OFFICERS	To date, health effects of exposure to the September 11, 2001 disaster in New York City have been studied in specific groups, but no studies have estimated its impact across the different exposed populations. This report provides an overview of the World Trade Center Health Registry (WTCHR) enrollees, their exposures, and their respiratory and mental health outcomes 2-3 years post-9/11. Results are extrapolated to the estimated universe of people eligible to enroll in the WTCHR to determine magnitude of impact. Building occupants, persons on the street or in transit in lower Manhattan on 9/11, local residents, rescue and recovery workers/volunteers, and area school children and staff were interviewed and enrolled in the WTCHR between September 2003 and November 2004. A total of 71,437 people enrolled in the WTCHR, for 17.4% coverage of the estimated eligible exposed population (nearly 410,000); 30% were recruited from lists, and 70% were self-identified. Many reported being in the dust cloud from the collapsing WTC Towers (51%), witnessing traumatic events (70%), or sustaining an injury (13%). After 9/11, 67% of adult enrollees reported new or worsening respiratory symptoms, 3% reported newly diagnosed asthma, 16% screened positive for probable posttraumatic stress disorder (PTSD), and 8% for serious psychological distress (SPD). Newly diagnosed asthma was most common among rescue and recovery workers who worked on the debris pile (4.1%). PTSD was higher among those who reported Hispanic ethnicity (30%), household income <$25,000 (31%), or being injured (35%). Using previously published estimates of the total number of exposed people per WTCHR eligibility criteria, we estimate between 3,800 and 12,600 adults experienced newly diagnosed asthma and 34,600-70,200 adults experienced PTSD following the attacks, suggesting extensive adverse health impacts beyond the immediate deaths and injuries from the acute event.	77	101	2008	30	10.1007/s11524-008-9317-4	Public, Environmental & Occupational Health; General & Internal Medicine
Doctor-patient communication, health-related beliefs, and adherence in glaucoma. Objective: To use multiple data sources to determine drivers of patient adherence to topical ocular hypotensive therapy. Design: Retrospective database and chart reviews in combination with prospective patient surveys. Diverse medical environments where insured patients in the research database seek care. Participants: Three hundred patients with a new claim diagnosis for open-angle glaucoma who initially were prescribed one of three prostaglandins and 103 physicians participating in the same medical plans. Methods: A structured interview addressing self-reported adherence, experiences with medication, communication with the physician, and health-related beliefs associated with adherence behavior was administered to surveyed patients. Phone interviews were conducted with participating ophthalmologists. Main Outcome Measure: Of adherence, medication possession ratio. Results: Eight variables were associated independently with a lower medication possession ratio: (1) hearing all of what you know about glaucoma from your doctor (compared with some or nothing); (2) not believing that reduced vision is a risk of not taking medication as recommended; (3) having a problem paying for medications; (4) difficulty while traveling or away from home; (5) not acknowledging stinging and burning; (6) being nonwhite; (7) receiving samples; and (8) not receiving a phone call visit reminder. The multivariate model explained 21% of the variance. Conclusions: These findings indicate that doctor-patient communications and health-related beliefs of patients contribute to patient adherence. Patient learning styles that are associated with less concern about the future effects of glaucoma and the risks of not taking medications are associated with lower adherence. Specifically, knowledge about potential vision loss from glaucoma is a critical element that tends to be missed by more passive doctor-dependent patients who tend to be poorly adherent. These findings suggest that educational efforts in the office may improve patient adherence to medical therapies.. behavioral skills model| managed care population| pharmacy claims data| open-angle glaucoma| quality-of-life| antiretroviral therapy| future-directions| asthma-treatment| chronic disease| empirical-test.	AUG-2008	behavioral skills model| managed care population| pharmacy claims data| open-angle glaucoma| quality-of-life| antiretroviral therapy| future-directions| asthma-treatment| chronic disease| empirical-test	Friedman, DS; Hahn, SR; Gelb, L; Tan, J; Shah, SN; Kim, EE; Zimmerman, TJ; Quigley, HA	Doctor-patient communication, health-related beliefs, and adherence in glaucoma		OPHTHALMOLOGY		BEHAVIORAL SKILLS MODEL; MANAGED CARE POPULATION; PHARMACY CLAIMS DATA; OPEN-ANGLE GLAUCOMA; QUALITY-OF-LIFE; ANTIRETROVIRAL THERAPY; FUTURE-DIRECTIONS; ASTHMA-TREATMENT; CHRONIC DISEASE; EMPIRICAL-TEST	Objective: To use multiple data sources to determine drivers of patient adherence to topical ocular hypotensive therapy. Design: Retrospective database and chart reviews in combination with prospective patient surveys. Diverse medical environments where insured patients in the research database seek care. Participants: Three hundred patients with a new claim diagnosis for open-angle glaucoma who initially were prescribed one of three prostaglandins and 103 physicians participating in the same medical plans. Methods: A structured interview addressing self-reported adherence, experiences with medication, communication with the physician, and health-related beliefs associated with adherence behavior was administered to surveyed patients. Phone interviews were conducted with participating ophthalmologists. Main Outcome Measure: Of adherence, medication possession ratio. Results: Eight variables were associated independently with a lower medication possession ratio: (1) hearing all of what you know about glaucoma from your doctor (compared with some or nothing); (2) not believing that reduced vision is a risk of not taking medication as recommended; (3) having a problem paying for medications; (4) difficulty while traveling or away from home; (5) not acknowledging stinging and burning; (6) being nonwhite; (7) receiving samples; and (8) not receiving a phone call visit reminder. The multivariate model explained 21% of the variance. Conclusions: These findings indicate that doctor-patient communications and health-related beliefs of patients contribute to patient adherence. Patient learning styles that are associated with less concern about the future effects of glaucoma and the risks of not taking medications are associated with lower adherence. Specifically, knowledge about potential vision loss from glaucoma is a critical element that tends to be missed by more passive doctor-dependent patients who tend to be poorly adherent. These findings suggest that educational efforts in the office may improve patient adherence to medical therapies.	81	101	2008	8	10.1016/j.ophtha.2007.11.023	Ophthalmology
Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is an important fragrance chemical, frequently used in scented products because of its fresh, flowery odor. Linalool is an unsaturated hydrocarbon and is therefore susceptible to oxidation in the presence of air. The primary oxidation products, that is, hydroperoxides, formed in the autoxidation process, are reactive compounds that can be suspected to act as sensitizers. In the present investigation, we studied the autoxidation of linalool with emphasis on the formation of hydroperoxides. The oxidation products were isolated using flash chromatography and preparative HPLC and were identified with NMR and GC/ MS, using synthesized reference compounds. Two hydroperoxides and several different secondary oxidation products were identified, among which some contain structural features that make them potential allergens. The amounts of linalool and the major oxidation products were quantified over time, using GC and an HPLC-method, suitable for the analysis of thermolabile primary oxidation products. The hydroperoxide 7-hydroperoxy-3,7-dimethylocta-1,5-diene-3-ol was found to be present in 15% in an oxidized sample. The local lymph node assay (LLNA) was used to investigate the sensitizing potential of pure linalool, two samples of air-exposed linalool, and oxidation products of linalool (an alpha,beta-unsaturated aldehyde, a mixture of two hydroperoxides, and an alcohol). Pure linalool showed no sensitizing potential. The air-exposed samples of linalool produced clearly positive responses, and the hydroperoxides were the strongest allergens of the tested oxidation products. The study demonstrates the importance of autoxidation on the sensitizing potential of linalool. We also conclude that the sensitizing potential differs with the composition of the oxidation mixture and thus with the air exposure time.. lymph-node assay| 15-hydroperoxyabietic acid| d-limonene| hydroperoxide| autoxidation| rearrangement| monoterpenes| mechanism| aldehydes| responses.	DEC-2004	lymph-node assay| 15-hydroperoxyabietic acid| d-limonene| hydroperoxide| autoxidation| rearrangement| monoterpenes| mechanism| aldehydes| responses	Skold, M; Borje, A; Harambasic, E; Karlberg, AT	Contact allergens formed on air exposure of linalool. Identification and quantification of primary and secondary oxidation products and the effect on skin sensitization		CHEMICAL RESEARCH IN TOXICOLOGY		LYMPH-NODE ASSAY; 15-HYDROPEROXYABIETIC ACID; D-LIMONENE; HYDROPEROXIDE; AUTOXIDATION; REARRANGEMENT; MONOTERPENES; MECHANISM; ALDEHYDES; RESPONSES	Linalool (3,7-dimethyl-1,6-octadien-3-ol) is an important fragrance chemical, frequently used in scented products because of its fresh, flowery odor. Linalool is an unsaturated hydrocarbon and is therefore susceptible to oxidation in the presence of air. The primary oxidation products, that is, hydroperoxides, formed in the autoxidation process, are reactive compounds that can be suspected to act as sensitizers. In the present investigation, we studied the autoxidation of linalool with emphasis on the formation of hydroperoxides. The oxidation products were isolated using flash chromatography and preparative HPLC and were identified with NMR and GC/ MS, using synthesized reference compounds. Two hydroperoxides and several different secondary oxidation products were identified, among which some contain structural features that make them potential allergens. The amounts of linalool and the major oxidation products were quantified over time, using GC and an HPLC-method, suitable for the analysis of thermolabile primary oxidation products. The hydroperoxide 7-hydroperoxy-3,7-dimethylocta-1,5-diene-3-ol was found to be present in 15% in an oxidized sample. The local lymph node assay (LLNA) was used to investigate the sensitizing potential of pure linalool, two samples of air-exposed linalool, and oxidation products of linalool (an alpha,beta-unsaturated aldehyde, a mixture of two hydroperoxides, and an alcohol). Pure linalool showed no sensitizing potential. The air-exposed samples of linalool produced clearly positive responses, and the hydroperoxides were the strongest allergens of the tested oxidation products. The study demonstrates the importance of autoxidation on the sensitizing potential of linalool. We also conclude that the sensitizing potential differs with the composition of the oxidation mixture and thus with the air exposure time.	41	101	2004	9	10.1021/tx049831z	Pharmacology & Pharmacy; Chemistry; Toxicology
Air pollution, health, and socio-economic status: the effect of outdoor air quality on childhood asthma. This paper estimates the effect of air pollution on child hospitalizations for asthma using naturally occurring seasonal variations in pollution within zip codes. Of the pollutants considered, carbon monoxide (CO) has a significant effect on asthma for children ages 1-18: if 1998 pollution levels were at their 1992 levels, there would be a 5-14% increase in asthma admissions. Also, households respond to information about pollution with avoidance behavior, suggesting it is important to account for these endogenous responses when measuring the effect of pollution on health. Finally, the effect of pollution is greater for children of lower socio-economic status (SES), indicating that pollution is one potential mechanism by which SES affects health. (C) 2004 Elsevier B.V. All rights reserved.. pollution| health| asthma| socio-economic status| avoidance behavior| zip code fixed effect|acute respiratory illness| emergency-room visits| children| disease| cities| impact.	NOV-2004	pollution| health| asthma| socio-economic status| avoidance behavior| zip code fixed effect|acute respiratory illness| emergency-room visits| children| disease| cities| impact	Neidell, MJ	Air pollution, health, and socio-economic status: the effect of outdoor air quality on childhood asthma		JOURNAL OF HEALTH ECONOMICS	pollution; health; asthma; socio-economic status; avoidance behavior; zip code fixed effect	ACUTE RESPIRATORY ILLNESS; EMERGENCY-ROOM VISITS; CHILDREN; DISEASE; CITIES; IMPACT	This paper estimates the effect of air pollution on child hospitalizations for asthma using naturally occurring seasonal variations in pollution within zip codes. Of the pollutants considered, carbon monoxide (CO) has a significant effect on asthma for children ages 1-18: if 1998 pollution levels were at their 1992 levels, there would be a 5-14% increase in asthma admissions. Also, households respond to information about pollution with avoidance behavior, suggesting it is important to account for these endogenous responses when measuring the effect of pollution on health. Finally, the effect of pollution is greater for children of lower socio-economic status (SES), indicating that pollution is one potential mechanism by which SES affects health. (C) 2004 Elsevier B.V. All rights reserved.	42	101	2004	28	10.1016/j.jhealeco.2004.05.002	Business & Economics; Health Care Sciences & Services
Natural history and familial relationships of infant spilling to 9 years of age. Objectives. To determine the natural history of infant spilling (regurgitation/vomiting) during the first 2 years of life and to determine the relationship between infant spilling and gastroesophageal reflux (GER) symptoms at 9 years of age. Methods. A prospective birth cohort was followed with daily symptom diaries during the first 2 years of life and reviewed at 9 years of age (range: 8-11 years). The prevalence of infant spilling during the first 2 years of life, the prevalence of GER symptoms between 8 and 11 years of age (mean age: 9.7 years), relative risk of infant spilling predisposing to GER symptoms at 9 years of age, and prevalence of maternal GER symptoms and relationship with infant spilling and GER at 9 years of age were measured. Results. A total of 693 children who represented 83% of an original sample of 836 children and were followed for 2 years from birth with daily symptom diaries were contacted at 9 (8-11) years of age. Spilling of most feeds each day was common in infancy and reached a peak prevalence of 41% between 3 and 4 months of age and thereafter declined to <5% between 13 and 14 months of age. Infants with spilling on 90 days or more during the first 2 years of life (classified as frequent spilling) were more likely to have GER symptoms at 9 years of age. Children with frequent infant spilling, compared with those with no spilling, had a relative risk of 2.3 (95% confidence interval [CI]: 1.3-4.0) of 1 or more GER symptoms at 9 years of age, 4.6 (95% CI: 1.5-13.8) for heartburn, 2.7 (95% CI: 1.4-5.5) for vomiting, and 4.7 (95% CI: 1.6-14.0) for acid regurgitation. Gender, breastfeeding, and environmental tobacco smoke exposure were not significant factors related to infant spilling. Prepregnancy smoking and smoking in the same room as the child at the 9-month and 18-month follow-ups had a significant effect on GER symptoms at 9 years of age. Infant spilling and GER at 9 years of age were significantly related to maternal GER symptoms but not to paternal GER symptoms. Conclusions. Spilling in infancy is very common, but the majority of children settle by 13 to 14 months of age. However, those with frequent spilling (> 90 days) are more likely to have GER symptoms at 9 years of age. In addition, a maternal history of GER was significantly related both to infant spilling and to GER at 9 years, suggesting that a genetic component may be involved. Physicians should consider studying children with a history of frequent infant spilling to determine whether this group is at increased risk for GER disease.. children| gastroesophageal reflux| natural history|pediatric gastroesophageal reflux| barretts-esophagus| children| prevalence| symptoms| adenocarcinoma| disease| asthma| questionnaire| childhood.	JUN-2002	children| gastroesophageal reflux| natural history|pediatric gastroesophageal reflux| barretts-esophagus| children| prevalence| symptoms| adenocarcinoma| disease| asthma| questionnaire| childhood	Martin, AJ; Pratt, N; Kennedy, JD; Ryan, P; Ruffin, RE; Miles, H; Marley, J	Natural history and familial relationships of infant spilling to 9 years of age		PEDIATRICS	children; gastroesophageal reflux; natural history	PEDIATRIC GASTROESOPHAGEAL REFLUX; BARRETTS-ESOPHAGUS; CHILDREN; PREVALENCE; SYMPTOMS; ADENOCARCINOMA; DISEASE; ASTHMA; QUESTIONNAIRE; CHILDHOOD	Objectives. To determine the natural history of infant spilling (regurgitation/vomiting) during the first 2 years of life and to determine the relationship between infant spilling and gastroesophageal reflux (GER) symptoms at 9 years of age. Methods. A prospective birth cohort was followed with daily symptom diaries during the first 2 years of life and reviewed at 9 years of age (range: 8-11 years). The prevalence of infant spilling during the first 2 years of life, the prevalence of GER symptoms between 8 and 11 years of age (mean age: 9.7 years), relative risk of infant spilling predisposing to GER symptoms at 9 years of age, and prevalence of maternal GER symptoms and relationship with infant spilling and GER at 9 years of age were measured. Results. A total of 693 children who represented 83% of an original sample of 836 children and were followed for 2 years from birth with daily symptom diaries were contacted at 9 (8-11) years of age. Spilling of most feeds each day was common in infancy and reached a peak prevalence of 41% between 3 and 4 months of age and thereafter declined to <5% between 13 and 14 months of age. Infants with spilling on 90 days or more during the first 2 years of life (classified as frequent spilling) were more likely to have GER symptoms at 9 years of age. Children with frequent infant spilling, compared with those with no spilling, had a relative risk of 2.3 (95% confidence interval [CI]: 1.3-4.0) of 1 or more GER symptoms at 9 years of age, 4.6 (95% CI: 1.5-13.8) for heartburn, 2.7 (95% CI: 1.4-5.5) for vomiting, and 4.7 (95% CI: 1.6-14.0) for acid regurgitation. Gender, breastfeeding, and environmental tobacco smoke exposure were not significant factors related to infant spilling. Prepregnancy smoking and smoking in the same room as the child at the 9-month and 18-month follow-ups had a significant effect on GER symptoms at 9 years of age. Infant spilling and GER at 9 years of age were significantly related to maternal GER symptoms but not to paternal GER symptoms. Conclusions. Spilling in infancy is very common, but the majority of children settle by 13 to 14 months of age. However, those with frequent spilling (> 90 days) are more likely to have GER symptoms at 9 years of age. In addition, a maternal history of GER was significantly related both to infant spilling and to GER at 9 years, suggesting that a genetic component may be involved. Physicians should consider studying children with a history of frequent infant spilling to determine whether this group is at increased risk for GER disease.	36	101	2002	7	10.1542/peds.109.6.1061	Pediatrics
Treatment of varicose veins by foam sclerotherapy: Two clinical series. Objective: To assess the efficacy and safety of sclerotherapy of varicose veins (VV) with sclerosing foam (SF) made using Tessari's method (three-way tap and two plastic syringes). Design: Two multi-centre prospective clinical series were documented (CS1 and CS2). In CS1, which ran from March to December 2000, 177 patients (39 men, 138 women), mean age 56 years, were treated in three centres for VV related to incompetence of saphenous veins, recurrence, perforators or collaterals. Conventional or duplex-guided sclerotherapy was performed using SF made of purified sodium tetradecyl sulphate (PSTS) 0.2-3% (Fibro-vein, STD Pharmaceuticals, UK) and air. An average of 1.6 (SD 0.8) sessions per patient were performed and 2.9 (SD 1.0) ml of SF (i.e. 0.6 ml of PSTS) per session was employed. An elastic stocking providing 20-30 or 30-40 mmHg compression was worn by patients following treatment. All the patients were reviewed (clinical examination and colour duplex ultrasonography) at 1 month. Sixty-six patients had a further follow-up 45-370 days after treatment. The 17 patients in CS2, a multi-centre study, were treated in March and April 2001. An independent observer assessed patients with major VV (CEAP and VV type distribution similar to CS1) before and after the treatment, and also observed the treatment, which was carried out using the technique employed in CS1. Results: In CS1 at 1 month follow-up there was: (A) obliteration of the vessel or antegrade flow in 161 (91%) patients, (13) minimal retrograde flow in the treated vein without visible VV, in 15 (8.4%) cases and (C) persistence of vessel patency with retrograde flow and visible VV (failure) in 1 (0.6%) case. At 45-370 days (mean 138 days) follow-up results were: type A in 44 (67%) cases, type B in 17 (26%) cases and type C in 5 (8%) cases. The main complications were extension of sclerothrombus from superficial to deep veins (n = 2), allergy (n = 1), malaise (n = 1) and scotoma (n = 1). In CS2 at 30 days follow-up 100% of the treated venous segments had a type A outcome after an average of 1.4 sessions. No relevant complication occurred in this series. Conclusions: Sclerotherapy of major VV by means of SF prepared by Tessari's method is a safe and effective form of treatment. Low doses and a low concentration of drug may be successfully employed. Further studies are needed to establish the long-term results and overall safety of this form of foam sclerotherapy.. sclerosing foam| sclerotherapy| ultrasound imaging| varicose veins|ultrasound-guided sclerotherapy| sclerosing foam| determinants.	2002	sclerosing foam| sclerotherapy| ultrasound imaging| varicose veins|ultrasound-guided sclerotherapy| sclerosing foam| determinants	Cavezzi, A; Frullini, A; Ricci, S; Tessari, L	Treatment of varicose veins by foam sclerotherapy: Two clinical series		PHLEBOLOGY	sclerosing foam; sclerotherapy; ultrasound imaging; varicose veins	ULTRASOUND-GUIDED SCLEROTHERAPY; SCLEROSING FOAM; DETERMINANTS	Objective: To assess the efficacy and safety of sclerotherapy of varicose veins (VV) with sclerosing foam (SF) made using Tessari's method (three-way tap and two plastic syringes). Design: Two multi-centre prospective clinical series were documented (CS1 and CS2). In CS1, which ran from March to December 2000, 177 patients (39 men, 138 women), mean age 56 years, were treated in three centres for VV related to incompetence of saphenous veins, recurrence, perforators or collaterals. Conventional or duplex-guided sclerotherapy was performed using SF made of purified sodium tetradecyl sulphate (PSTS) 0.2-3% (Fibro-vein, STD Pharmaceuticals, UK) and air. An average of 1.6 (SD 0.8) sessions per patient were performed and 2.9 (SD 1.0) ml of SF (i.e. 0.6 ml of PSTS) per session was employed. An elastic stocking providing 20-30 or 30-40 mmHg compression was worn by patients following treatment. All the patients were reviewed (clinical examination and colour duplex ultrasonography) at 1 month. Sixty-six patients had a further follow-up 45-370 days after treatment. The 17 patients in CS2, a multi-centre study, were treated in March and April 2001. An independent observer assessed patients with major VV (CEAP and VV type distribution similar to CS1) before and after the treatment, and also observed the treatment, which was carried out using the technique employed in CS1. Results: In CS1 at 1 month follow-up there was: (A) obliteration of the vessel or antegrade flow in 161 (91%) patients, (13) minimal retrograde flow in the treated vein without visible VV, in 15 (8.4%) cases and (C) persistence of vessel patency with retrograde flow and visible VV (failure) in 1 (0.6%) case. At 45-370 days (mean 138 days) follow-up results were: type A in 44 (67%) cases, type B in 17 (26%) cases and type C in 5 (8%) cases. The main complications were extension of sclerothrombus from superficial to deep veins (n = 2), allergy (n = 1), malaise (n = 1) and scotoma (n = 1). In CS2 at 30 days follow-up 100% of the treated venous segments had a type A outcome after an average of 1.4 sessions. No relevant complication occurred in this series. Conclusions: Sclerotherapy of major VV by means of SF prepared by Tessari's method is a safe and effective form of treatment. Low doses and a low concentration of drug may be successfully employed. Further studies are needed to establish the long-term results and overall safety of this form of foam sclerotherapy.	26	101	2002	6	10.1007/BF02667958	Surgery; Cardiovascular System & Cardiology
Comparison of the structural and inflammatory features of COPD and asthma. At least three conditions contribute to COPD, (1) Chronic bronchitis (mucous hypersecretion) is an inflammatory condition in which CD8+ T-lymphocytes, neutrophils, and CD68+ monocytes/macrophages predominate. The condition is defined clinically by the presence of chronic cough and recurrent increases in bronchial secretions sufficient to cause expectoration, There is enlargement of mucus-secreting glands and goblet cell hyperplasia, which can occur in the absence of airflow limitation. (2) Adult chronic bronchiolitis (small or peripheral airways disease) is an inflammatory condition of small bronchi and bronchioli in which there are predominantly CD8+ and pigmented macrophages, The functional defect is difficult to detect clinically but may be recognized by sophisticated tests of small airway function. There is mucous metaplasia, enlargement of the mass of bronchiolar smooth muscle, and loss of alveolar attachments. (3) Emphysema is an inflammatory condition of the alveoli in which T-lymphocytes, neutrophils, and pigmented alveolar macrophages are involved, associated with the release of excessive amounts of elastases. It is defined anatomically by permanent, destructive enlargement of airspaces distal to terminal bronchioli without obvious fibrosis. In contrast, asthma is a clinical syndrome characterized by allergic inflammation of bronchi and bronchioli in which CD4+ (helper) T-lymphocytes and eosinophils predominate. There is increased production and release of interleukin (IL)-4 and IL-5, which is referred to as a The-type response. There is usually increased tracheobronchial responsiveness to a variety of stimuli, and the condition is usually manifest as variable airflow obstruction. While differences between COPD and asthma have been highlighted, new data are emerging that indicate there may also be similarities.. airway asthma| biopsy| chronic bronchitis| copd| emphysema| inflammation|obstructive pulmonary-disease| air-flow obstruction| chronic mucus hypersecretion| activated lymphocytes-t| chronic-bronchitis| peripheral airways| cigarette smokers| atopic asthma| eosinophilic bronchitis| emphysematous lungs.	MAY-2000	airway asthma| biopsy| chronic bronchitis| copd| emphysema| inflammation|obstructive pulmonary-disease| air-flow obstruction| chronic mucus hypersecretion| activated lymphocytes-t| chronic-bronchitis| peripheral airways| cigarette smokers| atopic asthma| eosinophilic bronchitis| emphysematous lungs	Jeffery, PK	Comparison of the structural and inflammatory features of COPD and asthma		CHEST	airway asthma; biopsy; chronic bronchitis; COPD; emphysema; inflammation	OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; CHRONIC MUCUS HYPERSECRETION; ACTIVATED LYMPHOCYTES-T; CHRONIC-BRONCHITIS; PERIPHERAL AIRWAYS; CIGARETTE SMOKERS; ATOPIC ASTHMA; EOSINOPHILIC BRONCHITIS; EMPHYSEMATOUS LUNGS	At least three conditions contribute to COPD, (1) Chronic bronchitis (mucous hypersecretion) is an inflammatory condition in which CD8+ T-lymphocytes, neutrophils, and CD68+ monocytes/macrophages predominate. The condition is defined clinically by the presence of chronic cough and recurrent increases in bronchial secretions sufficient to cause expectoration, There is enlargement of mucus-secreting glands and goblet cell hyperplasia, which can occur in the absence of airflow limitation. (2) Adult chronic bronchiolitis (small or peripheral airways disease) is an inflammatory condition of small bronchi and bronchioli in which there are predominantly CD8+ and pigmented macrophages, The functional defect is difficult to detect clinically but may be recognized by sophisticated tests of small airway function. There is mucous metaplasia, enlargement of the mass of bronchiolar smooth muscle, and loss of alveolar attachments. (3) Emphysema is an inflammatory condition of the alveoli in which T-lymphocytes, neutrophils, and pigmented alveolar macrophages are involved, associated with the release of excessive amounts of elastases. It is defined anatomically by permanent, destructive enlargement of airspaces distal to terminal bronchioli without obvious fibrosis. In contrast, asthma is a clinical syndrome characterized by allergic inflammation of bronchi and bronchioli in which CD4+ (helper) T-lymphocytes and eosinophils predominate. There is increased production and release of interleukin (IL)-4 and IL-5, which is referred to as a The-type response. There is usually increased tracheobronchial responsiveness to a variety of stimuli, and the condition is usually manifest as variable airflow obstruction. While differences between COPD and asthma have been highlighted, new data are emerging that indicate there may also be similarities.	84	101	2000	10	10.1378/chest.117.5_suppl_1.251S	General & Internal Medicine; Respiratory System
Quantitative structural and biochemical analyses of tight junction dynamics following exposure of epithelial cells to house dust mite allergen Der p 1. Background House dust mite allergen Der p 1 is a cysteine peptidase. Previously, we have suggested that the proteolytic activity of this allergen may contribute to asthma by damaging the barrier formed by the airways epithelium. Objective The present study applied novel techniques to compare changes in permeability with quantitative events in tight junctions (TJs) and desmosomes (DMs) of epithelial cells exposed to Der p 1. Methods Confluent monolayers of Madin-Darby canine kidney (MDCK) and 16HBE14o-human bronchial epithelial cells were used as experimental models. Permeability was estimated from mannitol clearance. Digital imaging with quantification of TJs and DMs was achieved by fluorescent antibody staining and 2-photon molecular excitation microscopy (2PMEM). Biochemical changes in TJs were studied by immunoblotting, radiolabelling and immunoprecipitation. Results Der p 1 caused a time-dependent breakage of TJs and reduction in their content of the protein ZO-1. Reduction in ZO-1 immunofluorescence at TJs occurred with a small increase in the amount of diffuse, cytoplasmic immunoreactive ZO-1 staining. Morpho-logical changes in TJs occurred in synchrony with increases in epithelial permeability. DM puncta increased both in size and intensity of staining. Immunoblotting demonstrated that the disruption of TJ morphology was associated with cleavage of ZO-1 and occludin. Cells recovered from allergen exposure by de novo synthesis of occludin. Conclusion Der p 1 could contribute to sensitization and allergic responses by degrading the function of the airway epithelial barrier.. house dust mite| allergen| der p 1| tight junction| epithelium| asthma| cysteine peptidase|dermatophagoides-pteronyssinus| membrane-protein| occludin| permeability| sequence| der-p-1| fibroblasts| disruption| component| claudin-1.	MAY-2000	house dust mite| allergen| der p 1| tight junction| epithelium| asthma| cysteine peptidase|dermatophagoides-pteronyssinus| membrane-protein| occludin| permeability| sequence| der-p-1| fibroblasts| disruption| component| claudin-1	Wan, H; Winton, HL; Soeller, C; Gruenert, DC; Thompson, PJ; Cannell, MB; Stewart, GA; Garrod, DR; Robinson, C	Quantitative structural and biochemical analyses of tight junction dynamics following exposure of epithelial cells to house dust mite allergen Der p 1		CLINICAL AND EXPERIMENTAL ALLERGY	house dust mite; allergen; Der p 1; tight junction; epithelium; asthma; cysteine peptidase	DERMATOPHAGOIDES-PTERONYSSINUS; MEMBRANE-PROTEIN; OCCLUDIN; PERMEABILITY; SEQUENCE; DER-P-1; FIBROBLASTS; DISRUPTION; COMPONENT; CLAUDIN-1	Background House dust mite allergen Der p 1 is a cysteine peptidase. Previously, we have suggested that the proteolytic activity of this allergen may contribute to asthma by damaging the barrier formed by the airways epithelium. Objective The present study applied novel techniques to compare changes in permeability with quantitative events in tight junctions (TJs) and desmosomes (DMs) of epithelial cells exposed to Der p 1. Methods Confluent monolayers of Madin-Darby canine kidney (MDCK) and 16HBE14o-human bronchial epithelial cells were used as experimental models. Permeability was estimated from mannitol clearance. Digital imaging with quantification of TJs and DMs was achieved by fluorescent antibody staining and 2-photon molecular excitation microscopy (2PMEM). Biochemical changes in TJs were studied by immunoblotting, radiolabelling and immunoprecipitation. Results Der p 1 caused a time-dependent breakage of TJs and reduction in their content of the protein ZO-1. Reduction in ZO-1 immunofluorescence at TJs occurred with a small increase in the amount of diffuse, cytoplasmic immunoreactive ZO-1 staining. Morpho-logical changes in TJs occurred in synchrony with increases in epithelial permeability. DM puncta increased both in size and intensity of staining. Immunoblotting demonstrated that the disruption of TJ morphology was associated with cleavage of ZO-1 and occludin. Cells recovered from allergen exposure by de novo synthesis of occludin. Conclusion Der p 1 could contribute to sensitization and allergic responses by degrading the function of the airway epithelial barrier.	38	101	2000	14		Allergy; Immunology
Socioeconomic predictors of high allergen levels in homes in the greater Boston area. In the United States, childhood asthma morbidity and prevalence rates are the highest in less affluent urban minority communities. More than 80% of childhood asthmatics are allergic to one or more inhalant allergens. We evaluated whether socioeconomic status was associated with a differential in the levels and types of indoor home allergens. Dust samples for an ELISA allergen assay were collected from the homes of 499 families as part of a metropolitan Boston, Massachusetts, longitudinal birth cohort study of home allergens and asthma in children with a parental history of asthma or allergy. The proportion of homes with maximum home allergen levels in the highest category was 42% for dust mite allergen (greater than or equal to 10 mu g/g Der p 1 or Der f 1), 13% for cockroach allergen (greater than or equal to 2 U/g Bla g 1 or Bla g 2), 26% for cat allergen (greater than or equal to 8 mu g/g Fel d 1), and 20% for dog allergen (greater than or equal to 10 mu g/g Can f 1). Homes in the high-poverty area (> 20% of the population below the poverty level) were more likely to have high cockroach allergen levels than homes in the low-poverty area [51 vs. 3%; OR, 33; 95% confidence interval (CI), 12-90], but less likely co have high levels of dust mite allergen (16 vs. 53%; OR, 0.2; CI, 0.1-0.4). Lower family income, less maternal education, and race/ethnicity (black or Hispanic vs. white) were also associated with a lower risk of high dust mite levels and a greater risk of high cockroach allergen levels. Within a single U.S. metropolitan area we found marked between-community differences in the types of allergens present in the home, bur not necessarily in the overall burden of allergen exposure.. asthma| cat| cockroach| dog| dust mite| indoor allergens| inner city|inner-city children| house dust mites| risk-factors| affinity purification| cockroach allergen| indoor allergens| asthma mortality| united-states| p-i| exposure.	APR-2000	asthma| cat| cockroach| dog| dust mite| indoor allergens| inner city|inner-city children| house dust mites| risk-factors| affinity purification| cockroach allergen| indoor allergens| asthma mortality| united-states| p-i| exposure	Kitch, BT; Chew, G; Burge, HA; Muilenberg, ML; Weiss, ST; Platts-Mills, TAE; O'Connor, G; Gold, DR	Socioeconomic predictors of high allergen levels in homes in the greater Boston area		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; cat; cockroach; dog; dust mite; indoor allergens; inner city	INNER-CITY CHILDREN; HOUSE DUST MITES; RISK-FACTORS; AFFINITY PURIFICATION; COCKROACH ALLERGEN; INDOOR ALLERGENS; ASTHMA MORTALITY; UNITED-STATES; P-I; EXPOSURE	In the United States, childhood asthma morbidity and prevalence rates are the highest in less affluent urban minority communities. More than 80% of childhood asthmatics are allergic to one or more inhalant allergens. We evaluated whether socioeconomic status was associated with a differential in the levels and types of indoor home allergens. Dust samples for an ELISA allergen assay were collected from the homes of 499 families as part of a metropolitan Boston, Massachusetts, longitudinal birth cohort study of home allergens and asthma in children with a parental history of asthma or allergy. The proportion of homes with maximum home allergen levels in the highest category was 42% for dust mite allergen (greater than or equal to 10 mu g/g Der p 1 or Der f 1), 13% for cockroach allergen (greater than or equal to 2 U/g Bla g 1 or Bla g 2), 26% for cat allergen (greater than or equal to 8 mu g/g Fel d 1), and 20% for dog allergen (greater than or equal to 10 mu g/g Can f 1). Homes in the high-poverty area (> 20% of the population below the poverty level) were more likely to have high cockroach allergen levels than homes in the low-poverty area [51 vs. 3%; OR, 33; 95% confidence interval (CI), 12-90], but less likely co have high levels of dust mite allergen (16 vs. 53%; OR, 0.2; CI, 0.1-0.4). Lower family income, less maternal education, and race/ethnicity (black or Hispanic vs. white) were also associated with a lower risk of high dust mite levels and a greater risk of high cockroach allergen levels. Within a single U.S. metropolitan area we found marked between-community differences in the types of allergens present in the home, bur not necessarily in the overall burden of allergen exposure.	30	101	2000	7	10.2307/3454347	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Prospective Multicenter Study of Viral Etiology and Hospital Length of Stay in Children With Severe Bronchiolitis. Objective: To determine whether hospital length of stay (LOS) for acute bronchiolitis is influenced by the infecting pathogen. Design: A prospective observational cohort study was performed during 3 consecutive years. Setting: Sixteen US hospitals participated in the study. Participants: Children younger than 2 years hospitalized with bronchiolitis were included. Main Exposure: The results of nasopharyngeal aspirate polymerase chain reaction pathogen testing served as the main exposure. Main Outcome Measure: Hospital LOS was determined. Results: Of 2207 participants, 72.0% had respiratory syncytial virus (RSV) and 25.6% had human rhinovirus (HRV); the incidence of each of the other viruses and bacteria was 7.8% or less. Multiple pathogen infections were present in 29.8% of the children. There were 1866 children (84.5%) with RSV and/or HRV. Among these 1866 children, the median age was 4 months and 59.5% were male. The median LOS was 2 days (interquartile range, 1-4 days). Compared with children who had only RSV, an LOS of 3 or more days was less likely among children with HRV alone (adjusted odds ratio [AOR], 0.36; 95% CI, 0.20-0.63; P < .001) and those with HRV plus non-RSV pathogens (AOR, 0.39; 95% CI, 0.23-0.66; P < .001) but more likely among children with RSV plus HRV(AOR, 1.33; 95% CI, 1.02-1.73; P =. 04), controlling for 15 demographic and clinical factors. Conclusions: In this multicenter study of children hospitalized with bronchiolitis, RSV was the most common virus detected, but HRV was detected in one-quarter of the children. Since 1 in 3 children had multiple virus infections and HRV was associated with LOS, these data challenge the effectiveness of current RSV-based cohorting practices, the sporadic testing for HRV in bronchiolitis research, and current thinking that the infectious etiology of severe bronchiolitis does not affect short-term outcomes.. respiratory syncytial virus| real-time pcr| rhinovirus infection| human metapneumovirus| asthma development| clinical symptoms| disease severity| risk-factors| infants| expression.	AUG-2012	respiratory syncytial virus| real-time pcr| rhinovirus infection| human metapneumovirus| asthma development| clinical symptoms| disease severity| risk-factors| infants| expression	Mansbach, JM; Piedra, PA; Teach, SJ; Sullivan, AF; Forgey, T; Clark, S; Espinola, JA; Camargo, CA	Prospective Multicenter Study of Viral Etiology and Hospital Length of Stay in Children With Severe Bronchiolitis		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		RESPIRATORY SYNCYTIAL VIRUS; REAL-TIME PCR; RHINOVIRUS INFECTION; HUMAN METAPNEUMOVIRUS; ASTHMA DEVELOPMENT; CLINICAL SYMPTOMS; DISEASE SEVERITY; RISK-FACTORS; INFANTS; EXPRESSION	Objective: To determine whether hospital length of stay (LOS) for acute bronchiolitis is influenced by the infecting pathogen. Design: A prospective observational cohort study was performed during 3 consecutive years. Setting: Sixteen US hospitals participated in the study. Participants: Children younger than 2 years hospitalized with bronchiolitis were included. Main Exposure: The results of nasopharyngeal aspirate polymerase chain reaction pathogen testing served as the main exposure. Main Outcome Measure: Hospital LOS was determined. Results: Of 2207 participants, 72.0% had respiratory syncytial virus (RSV) and 25.6% had human rhinovirus (HRV); the incidence of each of the other viruses and bacteria was 7.8% or less. Multiple pathogen infections were present in 29.8% of the children. There were 1866 children (84.5%) with RSV and/or HRV. Among these 1866 children, the median age was 4 months and 59.5% were male. The median LOS was 2 days (interquartile range, 1-4 days). Compared with children who had only RSV, an LOS of 3 or more days was less likely among children with HRV alone (adjusted odds ratio [AOR], 0.36; 95% CI, 0.20-0.63; P < .001) and those with HRV plus non-RSV pathogens (AOR, 0.39; 95% CI, 0.23-0.66; P < .001) but more likely among children with RSV plus HRV(AOR, 1.33; 95% CI, 1.02-1.73; P =. 04), controlling for 15 demographic and clinical factors. Conclusions: In this multicenter study of children hospitalized with bronchiolitis, RSV was the most common virus detected, but HRV was detected in one-quarter of the children. Since 1 in 3 children had multiple virus infections and HRV was associated with LOS, these data challenge the effectiveness of current RSV-based cohorting practices, the sporadic testing for HRV in bronchiolitis research, and current thinking that the infectious etiology of severe bronchiolitis does not affect short-term outcomes.	45	100	2012	7	10.1001/archpediatrics.2011.1669	Pediatrics
Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment. Prospective birth cohort studies tracking asthma initiation and consolidation in community cohorts have identified viral infections occurring against a background of allergic sensitization to aeroallergens as a uniquely potent risk factor for the expression of acute severe asthma-like symptoms and for the ensuing development of asthma that can persist through childhood and into adulthood. A combination of recent experimental and human studies have suggested that underlying this bipartite process are a series of interactions between antiviral and atopic inflammatory pathways that are mediated by local activation of myeloid cell populations in the airway mucosa and the parallel programming and recruitment of their replacements from bone marrow. Targeting key components of these pathways at the appropriate stages of asthma provides new opportunities for the treatment of established asthma but, more crucially, for primary and secondary prevention of asthma during childhood.. fc-epsilon-ri| respiratory syncytial virus| plasmacytoid dendritic cells| house-dust-mite| innate immune-response| memory t-cells| lung-function| bone-marrow| childhood asthma| allergic sensitization.	MAY-2012	fc-epsilon-ri| respiratory syncytial virus| plasmacytoid dendritic cells| house-dust-mite| innate immune-response| memory t-cells| lung-function| bone-marrow| childhood asthma| allergic sensitization	Holt, PG; Sly, PD	Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment		NATURE MEDICINE		FC-EPSILON-RI; RESPIRATORY SYNCYTIAL VIRUS; PLASMACYTOID DENDRITIC CELLS; HOUSE-DUST-MITE; INNATE IMMUNE-RESPONSE; MEMORY T-CELLS; LUNG-FUNCTION; BONE-MARROW; CHILDHOOD ASTHMA; ALLERGIC SENSITIZATION	Prospective birth cohort studies tracking asthma initiation and consolidation in community cohorts have identified viral infections occurring against a background of allergic sensitization to aeroallergens as a uniquely potent risk factor for the expression of acute severe asthma-like symptoms and for the ensuing development of asthma that can persist through childhood and into adulthood. A combination of recent experimental and human studies have suggested that underlying this bipartite process are a series of interactions between antiviral and atopic inflammatory pathways that are mediated by local activation of myeloid cell populations in the airway mucosa and the parallel programming and recruitment of their replacements from bone marrow. Targeting key components of these pathways at the appropriate stages of asthma provides new opportunities for the treatment of established asthma but, more crucially, for primary and secondary prevention of asthma during childhood.	94	100	2012	10	10.1038/nm.2768	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Air pollution and airway disease. Epidemiological and toxicological research continues to support a link between urban air pollution and an increased incidence and/or severity of airway disease. Detrimental effects of ozone (O(3)), nitrogen dioxide (NO(2)) and particulate matter (PM), as well as traffic-related pollution as a whole, on respiratory symptoms and function are well documented. Not only do we have strong epidemiological evidence of a relationship between air pollution and exacerbation of asthma and respiratory morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), but recent studies, particularly in urban areas, have suggested a role for pollutants in the development of both asthma and COPD. Similarly, while prevalence and severity of atopic conditions appear to be more common in urban compared with rural communities, evidence is emerging that traffic-related pollutants may contribute to the development of allergy. Furthermore, numerous epidemiological and experimental studies suggest an association between exposure to NO(2), O(3), PM and combustion products of biomass fuels and an increased susceptibility to and morbidity from respiratory infection. Given the considerable contribution that traffic emissions make to urban air pollution researchers have sought to characterize the relative toxicity of traffic-related PM pollutants. Recent advances in mechanisms implicated in the association of air pollutants and airway disease include epigenetic alteration of genes by combustion-related pollutants and how polymorphisms in genes involved in antioxidant pathways and airway inflammation can modify responses to air pollution exposures. Other interesting epidemiological observations related to increased host susceptibility include a possible link between chronic PM exposure during childhood and vulnerability to COPD in adulthood, and that infants subjected to higher prenatal levels of air pollution may be at greater risk of developing respiratory conditions. While the characterization of pollutant components and sources promise to guide pollution control strategies, the identification of susceptible subpopulations will be necessary if targeted therapy/prevention of pollution-induced respiratory diseases is to be developed.. obstructive pulmonary-disease| glutathione-s-transferase| diesel exhaust particles| long-term exposure| polycyclic aromatic-hydrocarbons| respiratory syncytial virus| case-crossover analysis| emergency-room visits| tumor-necrosis-factor| lung-function.	AUG-2011	obstructive pulmonary-disease| glutathione-s-transferase| diesel exhaust particles| long-term exposure| polycyclic aromatic-hydrocarbons| respiratory syncytial virus| case-crossover analysis| emergency-room visits| tumor-necrosis-factor| lung-function	Kelly, FJ; Fussell, JC	Air pollution and airway disease		CLINICAL AND EXPERIMENTAL ALLERGY		OBSTRUCTIVE PULMONARY-DISEASE; GLUTATHIONE-S-TRANSFERASE; DIESEL EXHAUST PARTICLES; LONG-TERM EXPOSURE; POLYCYCLIC AROMATIC-HYDROCARBONS; RESPIRATORY SYNCYTIAL VIRUS; CASE-CROSSOVER ANALYSIS; EMERGENCY-ROOM VISITS; TUMOR-NECROSIS-FACTOR; LUNG-FUNCTION	Epidemiological and toxicological research continues to support a link between urban air pollution and an increased incidence and/or severity of airway disease. Detrimental effects of ozone (O(3)), nitrogen dioxide (NO(2)) and particulate matter (PM), as well as traffic-related pollution as a whole, on respiratory symptoms and function are well documented. Not only do we have strong epidemiological evidence of a relationship between air pollution and exacerbation of asthma and respiratory morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD), but recent studies, particularly in urban areas, have suggested a role for pollutants in the development of both asthma and COPD. Similarly, while prevalence and severity of atopic conditions appear to be more common in urban compared with rural communities, evidence is emerging that traffic-related pollutants may contribute to the development of allergy. Furthermore, numerous epidemiological and experimental studies suggest an association between exposure to NO(2), O(3), PM and combustion products of biomass fuels and an increased susceptibility to and morbidity from respiratory infection. Given the considerable contribution that traffic emissions make to urban air pollution researchers have sought to characterize the relative toxicity of traffic-related PM pollutants. Recent advances in mechanisms implicated in the association of air pollutants and airway disease include epigenetic alteration of genes by combustion-related pollutants and how polymorphisms in genes involved in antioxidant pathways and airway inflammation can modify responses to air pollution exposures. Other interesting epidemiological observations related to increased host susceptibility include a possible link between chronic PM exposure during childhood and vulnerability to COPD in adulthood, and that infants subjected to higher prenatal levels of air pollution may be at greater risk of developing respiratory conditions. While the characterization of pollutant components and sources promise to guide pollution control strategies, the identification of susceptible subpopulations will be necessary if targeted therapy/prevention of pollution-induced respiratory diseases is to be developed.	160	100	2011	13	10.1111/j.1365-2222.2011.03776.x	Allergy; Immunology
Epidemiology of Pancreatic Cancer: An Update. Pancreatic cancer, although infrequent, has a very poor prognosis, making it one of the 4 or 5 most common causes of cancer mortality in developed countries. Its incidence varies greatly across regions, which suggests that lifestyle factors such as diet, and environmental factors, such as vitamin D exposure, play a role. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer in the coming decades. Smoking is the most common known risk factor, causing 20-25% of all pancreatic tumors. Although a common cause of pancreatitis, heavy alcohol intake is associated only with a modest increased risk of pancreatic cancer. While viruses do not represent a major risk factor, people infected with Helicobacter pylori appeared to be at high risk of pancreatic cancer. Many factors associated with the metabolic syndrome, including overweight and obesity, impaired glucose tolerance, and long-standing diabetes also increase the risk disease, while atopic allergy and use of metformin as a treatment for diabetes have been associated with a reduced risk of pancreatic cancer. A family history of pancreatic cancer is associated with an increased risk of pancreatic cancer and it is estimated that 5-10% of patients with pancreatic cancer have an underlying germline disorder. Having a non-O blood group, another inherited characteristic, has also been steadily associated with an increased risk of pancreatic cancer. While many risk factors for pancreatic cancer are not modifiable, adopting a healthy lifestyle could substantially reduce pancreatic cancer risk. Copyright (C) 2010 S. Karger AG, Basel. pancreatic cancer| epidemiology| time trends| etiology| risk factors|body-mass index| abo blood-group| of-the-literature| vitamin-d status| physical-activity| cohort-consortium| pooled-analysis| periodontal-disease| diabetes-mellitus| cigarette-smoking.	2010	pancreatic cancer| epidemiology| time trends| etiology| risk factors|body-mass index| abo blood-group| of-the-literature| vitamin-d status| physical-activity| cohort-consortium| pooled-analysis| periodontal-disease| diabetes-mellitus| cigarette-smoking	Maisonneuve, P; Lowenfels, AB	Epidemiology of Pancreatic Cancer: An Update		DIGESTIVE DISEASES	Pancreatic cancer; Epidemiology; Time trends; Etiology; Risk factors	BODY-MASS INDEX; ABO BLOOD-GROUP; OF-THE-LITERATURE; VITAMIN-D STATUS; PHYSICAL-ACTIVITY; COHORT-CONSORTIUM; POOLED-ANALYSIS; PERIODONTAL-DISEASE; DIABETES-MELLITUS; CIGARETTE-SMOKING	Pancreatic cancer, although infrequent, has a very poor prognosis, making it one of the 4 or 5 most common causes of cancer mortality in developed countries. Its incidence varies greatly across regions, which suggests that lifestyle factors such as diet, and environmental factors, such as vitamin D exposure, play a role. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer in the coming decades. Smoking is the most common known risk factor, causing 20-25% of all pancreatic tumors. Although a common cause of pancreatitis, heavy alcohol intake is associated only with a modest increased risk of pancreatic cancer. While viruses do not represent a major risk factor, people infected with Helicobacter pylori appeared to be at high risk of pancreatic cancer. Many factors associated with the metabolic syndrome, including overweight and obesity, impaired glucose tolerance, and long-standing diabetes also increase the risk disease, while atopic allergy and use of metformin as a treatment for diabetes have been associated with a reduced risk of pancreatic cancer. A family history of pancreatic cancer is associated with an increased risk of pancreatic cancer and it is estimated that 5-10% of patients with pancreatic cancer have an underlying germline disorder. Having a non-O blood group, another inherited characteristic, has also been steadily associated with an increased risk of pancreatic cancer. While many risk factors for pancreatic cancer are not modifiable, adopting a healthy lifestyle could substantially reduce pancreatic cancer risk. Copyright (C) 2010 S. Karger AG, Basel	89	100	2010	12	10.1159/000320068	Gastroenterology & Hepatology
House Dust Mite Sublingual Immunotherapy The Role for Transforming Growth Factor-beta and Functional Regulatory T Cells. Rationale: Sublingual allergen-specific immunotherapy is gaining popularity for treatment of allergic diseases, but underlying immunological mechanisms are unresolved. Objectives: To perform detailed immunological investigation of sublingual house dust mite (HDM) immunotherapy. Methods: A 12-month randomized double-blind placebo-controlled study of sublingual HDM immunotherapy in 30 HDM-allergic subjects was performed, with 1-year open extension in 9 patients on active treatment. HDM-stimulated blood mononuclear cells were analyzed for proliferation, cytokines, and regulatory T cells (Tregs) by flow cytometry and ELISA. Effects of blocking transforming growth factor (TGF)-beta and IL-10 on proliferation were determined. Treg suppressor function and allergen-specific antibody levels were measured. Clinical efficacy was assessed by symptom, medication, and juniper quality-of-life scores. Measurements and Main Results: Allergen-induced CD4(+) T-cell division and IL-5 production were significantly decreased after 6- and 12-months' active treatment but not placebo. sTGF-beta RII blocked immunotherapy-induced suppression of allergen-specific T-cell proliferation, maximal at 6 months. Decreased allergen-specific CD4(+) T-cell proliferation and increased IL-10 secretion and serum Der p 2-specific IgG(4) were maximal at 24 months' active treatment. Treg (CD4(+)CD25(+)CD127(lo)/Foxp3(+)) function was demonstrated by suppression of allergen-specific effector T-cell (CD4(+)CD25(-)CD127(hi)) proliferation and cytokine production. Clinical efficacy of immunotherapy was supported by significantly decreased rhinitis symptom score, total asthma score, and Juniper quality-of-life score. Conclusions: This study establishes the novel finding that TGF-beta mediates the immunological suppression seen early in clinically effective sublingual HDM immunotherapy in addition to an increase in Tregs with suppressor function. Clinical trial registered with www.clinicaltrials.gov (NCT00250263).. allergen immunotherapy| sublingual administration| regulatory t cells| transforming growth factor-beta| t lymphocytes|grass-pollen immunotherapy| standardized 5-grass-pollen extract| systemic immunological changes| randomized controlled-trial| seasonal allergic rhinitis| double-blind| swallow immunotherapy| tgf-beta| immune-responses| clinical-efficacy.	NOV 15-2009	allergen immunotherapy| sublingual administration| regulatory t cells| transforming growth factor-beta| t lymphocytes|grass-pollen immunotherapy| standardized 5-grass-pollen extract| systemic immunological changes| randomized controlled-trial| seasonal allergic rhinitis| double-blind| swallow immunotherapy| tgf-beta| immune-responses| clinical-efficacy	O'Hehir, RE; Gardner, LM; de Leon, MP; Hales, BJ; Biondo, M; Douglass, JA; Rolland, JM; Sandrini, A	House Dust Mite Sublingual Immunotherapy The Role for Transforming Growth Factor-beta and Functional Regulatory T Cells		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	allergen immunotherapy; sublingual administration; regulatory T cells; transforming growth factor-beta; T lymphocytes	GRASS-POLLEN IMMUNOTHERAPY; STANDARDIZED 5-GRASS-POLLEN EXTRACT; SYSTEMIC IMMUNOLOGICAL CHANGES; RANDOMIZED CONTROLLED-TRIAL; SEASONAL ALLERGIC RHINITIS; DOUBLE-BLIND; SWALLOW IMMUNOTHERAPY; TGF-BETA; IMMUNE-RESPONSES; CLINICAL-EFFICACY	Rationale: Sublingual allergen-specific immunotherapy is gaining popularity for treatment of allergic diseases, but underlying immunological mechanisms are unresolved. Objectives: To perform detailed immunological investigation of sublingual house dust mite (HDM) immunotherapy. Methods: A 12-month randomized double-blind placebo-controlled study of sublingual HDM immunotherapy in 30 HDM-allergic subjects was performed, with 1-year open extension in 9 patients on active treatment. HDM-stimulated blood mononuclear cells were analyzed for proliferation, cytokines, and regulatory T cells (Tregs) by flow cytometry and ELISA. Effects of blocking transforming growth factor (TGF)-beta and IL-10 on proliferation were determined. Treg suppressor function and allergen-specific antibody levels were measured. Clinical efficacy was assessed by symptom, medication, and juniper quality-of-life scores. Measurements and Main Results: Allergen-induced CD4(+) T-cell division and IL-5 production were significantly decreased after 6- and 12-months' active treatment but not placebo. sTGF-beta RII blocked immunotherapy-induced suppression of allergen-specific T-cell proliferation, maximal at 6 months. Decreased allergen-specific CD4(+) T-cell proliferation and increased IL-10 secretion and serum Der p 2-specific IgG(4) were maximal at 24 months' active treatment. Treg (CD4(+)CD25(+)CD127(lo)/Foxp3(+)) function was demonstrated by suppression of allergen-specific effector T-cell (CD4(+)CD25(-)CD127(hi)) proliferation and cytokine production. Clinical efficacy of immunotherapy was supported by significantly decreased rhinitis symptom score, total asthma score, and Juniper quality-of-life score. Conclusions: This study establishes the novel finding that TGF-beta mediates the immunological suppression seen early in clinically effective sublingual HDM immunotherapy in addition to an increase in Tregs with suppressor function. Clinical trial registered with www.clinicaltrials.gov (NCT00250263).	71	100	2009	12	10.1164/rccm.200905-0686OC	General & Internal Medicine; Respiratory System
Trauma, Posttraumatic Stress Disorder, and Physical Illness: Findings from the General Population. Objective: To determine in a general population sample the differential impact on physical health of exposure to traumatic experiences and posttraumatic stress disorder (PTSD). Trauma exposure and PTSD have been associated with physical illness in specific populations, such as veterans. Methods: Medical histories including cardiovascular, endocrine, pulmonary, and other chronic diseases were obtained from 3171 adults living in the community. They were administered the PTSD module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and were assigned to three groups: no trauma (n = 1440); trauma, but no PTSD (n = 1669) and trauma with subsequent PTSD (n = 62). Results: After adjustments for sociodemographic factors, smoking, body mass index, blood pressure, depression, and alcohol use disorders, subjects with trauma history had higher odds ratios (ORs) for angina pectoris and heart failure (OR = 1.2; 95% Confidence Interval [CI] 1.1-1.3), stroke (OR = 1.2; 95 CI = 1.0-1.5), bronchitis, asthma, renal disease, and polyarthritis (ORs between 1.1 and 1.3) compared with nontraumatized participants. The PTSD positive subsample had increased ORs for angina (OR = 2.4; 95% CI = 1.3-4.5), heart failure (OR = 3.4; 95% CI = 1.9-6.0), bronchitis, asthma, liver, and peripheral arterial disease (ORs, range = 2.5-3.1). Conclusions: Our findings suggest a strong association between PTSD and cardiovascular and pulmonary diseases. Particular diagnostic and treatment attention should be paid to physical illness in PTSD positive patients in primary care, medical, and mental health settings.. trauma| posttraumatic stress disorder (ptsd)| physical health| cardiovascular and pulmonary disease| general population|adverse childhood experiences| heart-disease| primary-care| myocardial-infarction| psychiatric-disorders| vietnam veterans| health| symptoms| exposure| community.	NOV-DEC-2009	trauma| posttraumatic stress disorder (ptsd)| physical health| cardiovascular and pulmonary disease| general population|adverse childhood experiences| heart-disease| primary-care| myocardial-infarction| psychiatric-disorders| vietnam veterans| health| symptoms| exposure| community	Spitzer, C; Barnow, S; Volzke, H; John, U; Freyberger, HJ; Grabe, HJ	Trauma, Posttraumatic Stress Disorder, and Physical Illness: Findings from the General Population		PSYCHOSOMATIC MEDICINE	trauma; posttraumatic stress disorder (PTSD); physical health; cardiovascular and pulmonary disease; general population	ADVERSE CHILDHOOD EXPERIENCES; HEART-DISEASE; PRIMARY-CARE; MYOCARDIAL-INFARCTION; PSYCHIATRIC-DISORDERS; VIETNAM VETERANS; HEALTH; SYMPTOMS; EXPOSURE; COMMUNITY	Objective: To determine in a general population sample the differential impact on physical health of exposure to traumatic experiences and posttraumatic stress disorder (PTSD). Trauma exposure and PTSD have been associated with physical illness in specific populations, such as veterans. Methods: Medical histories including cardiovascular, endocrine, pulmonary, and other chronic diseases were obtained from 3171 adults living in the community. They were administered the PTSD module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and were assigned to three groups: no trauma (n = 1440); trauma, but no PTSD (n = 1669) and trauma with subsequent PTSD (n = 62). Results: After adjustments for sociodemographic factors, smoking, body mass index, blood pressure, depression, and alcohol use disorders, subjects with trauma history had higher odds ratios (ORs) for angina pectoris and heart failure (OR = 1.2; 95% Confidence Interval [CI] 1.1-1.3), stroke (OR = 1.2; 95 CI = 1.0-1.5), bronchitis, asthma, renal disease, and polyarthritis (ORs between 1.1 and 1.3) compared with nontraumatized participants. The PTSD positive subsample had increased ORs for angina (OR = 2.4; 95% CI = 1.3-4.5), heart failure (OR = 3.4; 95% CI = 1.9-6.0), bronchitis, asthma, liver, and peripheral arterial disease (ORs, range = 2.5-3.1). Conclusions: Our findings suggest a strong association between PTSD and cardiovascular and pulmonary diseases. Particular diagnostic and treatment attention should be paid to physical illness in PTSD positive patients in primary care, medical, and mental health settings.	45	100	2009	6	10.1097/PSY.0b013e3181bc76b5	Psychiatry; Psychology
Chronic Bronchitis, COPD, and Lung Function in Farmers The Role of Biological Agents. Background: Farmers have an increased risk of respiratory morbidity and mortality. The causal agents have not been fully established. Methods: In a cross-sectional study of 4,735 Norwegian farmers, we assessed respiratory symptoms and lung function. Atopy was assessed in a subsample (n = 1,213). Personal exposures to dust, fungal spores, actinomycete spores, endotoxins, bacteria, storage mites, (1 -> 3)-beta-D-glucans, fungal antigens, organic dust, inorganic dust, silica, ammonia, and hydrogen sulfide were measured for 127 randomly selected farms. Results: Compared to crop farmers, livestock farmers were more likely to have chronic bronchitis (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.4 to 2.6) and COPD (OR, 1.4; 95% CI, 1.1 to 1.7). FEV(1) (-41 mL; 95% CI, -75 to -7) was significantly reduced, but FVC (-15 mL; 95% CI, -54 to 24) was not. Exposure to most agents were predictors of respiratory morbidity, except FVC. Ammonia, hydrogen sulfide, and inorganic dust were most strongly associated in multiple regression models adjusted for coexposures, but the effects of specific biological agents could not be assessed in multiple regression models because they were too highly correlated. Farmers with atopy had a significantly lower FEV(1) (OR, -87 mL; 95% CI, -170 to -7), but atopy was not directly associated with chronic bronchitis, COPD, and FVC. However, the effects of farming and specific exposures on COPI) were substantially greater in farmers with atopy. Conclusions: Livestock farmers have an increased risk of chronic bronchitis, COPD, and reduced FEV(1). Ammonia, hydrogen sulfide, inorganic dust, and organic dust may be causally involved, but a role for specific biological agents cannot be excluded. Farmers with atopy appear more susceptible to develop farming-related COPI). (CHEST 2009; 136:716-725). obstructive pulmonary-disease| dose-response relationships| respiratory symptoms| animal farmers| exposure| endotoxin| workers| asthma| dust| environment.	SEP-2009	obstructive pulmonary-disease| dose-response relationships| respiratory symptoms| animal farmers| exposure| endotoxin| workers| asthma| dust| environment	Eduard, W; Pearce, N; Douwes, J	Chronic Bronchitis, COPD, and Lung Function in Farmers The Role of Biological Agents		CHEST		OBSTRUCTIVE PULMONARY-DISEASE; DOSE-RESPONSE RELATIONSHIPS; RESPIRATORY SYMPTOMS; ANIMAL FARMERS; EXPOSURE; ENDOTOXIN; WORKERS; ASTHMA; DUST; ENVIRONMENT	Background: Farmers have an increased risk of respiratory morbidity and mortality. The causal agents have not been fully established. Methods: In a cross-sectional study of 4,735 Norwegian farmers, we assessed respiratory symptoms and lung function. Atopy was assessed in a subsample (n = 1,213). Personal exposures to dust, fungal spores, actinomycete spores, endotoxins, bacteria, storage mites, (1 -> 3)-beta-D-glucans, fungal antigens, organic dust, inorganic dust, silica, ammonia, and hydrogen sulfide were measured for 127 randomly selected farms. Results: Compared to crop farmers, livestock farmers were more likely to have chronic bronchitis (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.4 to 2.6) and COPD (OR, 1.4; 95% CI, 1.1 to 1.7). FEV(1) (-41 mL; 95% CI, -75 to -7) was significantly reduced, but FVC (-15 mL; 95% CI, -54 to 24) was not. Exposure to most agents were predictors of respiratory morbidity, except FVC. Ammonia, hydrogen sulfide, and inorganic dust were most strongly associated in multiple regression models adjusted for coexposures, but the effects of specific biological agents could not be assessed in multiple regression models because they were too highly correlated. Farmers with atopy had a significantly lower FEV(1) (OR, -87 mL; 95% CI, -170 to -7), but atopy was not directly associated with chronic bronchitis, COPD, and FVC. However, the effects of farming and specific exposures on COPI) were substantially greater in farmers with atopy. Conclusions: Livestock farmers have an increased risk of chronic bronchitis, COPD, and reduced FEV(1). Ammonia, hydrogen sulfide, inorganic dust, and organic dust may be causally involved, but a role for specific biological agents cannot be excluded. Farmers with atopy appear more susceptible to develop farming-related COPI). (CHEST 2009; 136:716-725)	37	100	2009	10	10.1378/chest.08-2192	General & Internal Medicine; Respiratory System
The prevalence, cost and basis of food allergy across Europe. The development of effective management strategies to optimize the quality of life for allergic patients is currently hampered by a lack of good quality information. Estimates of how many individuals suffer from food allergy and the major foods involved vary widely and inadequacies of in vitro diagnostics make food challenges the only reliable means of diagnosis in many instances. The EuroPrevall project brings together a multidisciplinary partnership to address these issues. Cohorts spanning the main climatic regions of Europe are being developed in infants through a birth cohort, community surveys in school-age children and adults and an outpatient clinic study. Confirmatory double-blind placebo-controlled food challenge diagnosis is being undertaken using foods as they are eaten with titrated doses to allow no-effect and lowest-observable effect levels for allergenic foods to be determined. The cohorts will also facilitate validation of novel in vitro diagnostics through the development of the EuroPrevall Serum Bank. Complementary studies in Ghana, western Siberia, India and China will allow LIS to gain insights into how different dietary patterns and exposure to microorganisms affect food allergies. New instruments to assess the socioeconomic impact of food allergy are being developed in the project and their application in the clinical cohorts will allow, for the first time, an assessment to be made of the burden this disease places on allergy sufferers and their communities.. allergy| diagnosis| foods prevalence| socioeconomic|multicenter.	JUL-2007	allergy| diagnosis| foods prevalence| socioeconomic|multicenter	Mills, ENC; Mackie, AR; Burney, P; Beyer, K; Frewer, L; Madsen, C; Botjes, E; Crevel, RWR; van Ree, R	The prevalence, cost and basis of food allergy across Europe		ALLERGY	allergy; diagnosis; foods prevalence; socioeconomic	MULTICENTER	The development of effective management strategies to optimize the quality of life for allergic patients is currently hampered by a lack of good quality information. Estimates of how many individuals suffer from food allergy and the major foods involved vary widely and inadequacies of in vitro diagnostics make food challenges the only reliable means of diagnosis in many instances. The EuroPrevall project brings together a multidisciplinary partnership to address these issues. Cohorts spanning the main climatic regions of Europe are being developed in infants through a birth cohort, community surveys in school-age children and adults and an outpatient clinic study. Confirmatory double-blind placebo-controlled food challenge diagnosis is being undertaken using foods as they are eaten with titrated doses to allow no-effect and lowest-observable effect levels for allergenic foods to be determined. The cohorts will also facilitate validation of novel in vitro diagnostics through the development of the EuroPrevall Serum Bank. Complementary studies in Ghana, western Siberia, India and China will allow LIS to gain insights into how different dietary patterns and exposure to microorganisms affect food allergies. New instruments to assess the socioeconomic impact of food allergy are being developed in the project and their application in the clinical cohorts will allow, for the first time, an assessment to be made of the burden this disease places on allergy sufferers and their communities.	20	100	2007	6	10.1111/j.1398-9995.2007.01425.x	Allergy; Immunology
Changes in prevalence of asthma and allergies among children and adolescents in Italy: 1994-2002. BACKGROUND. Several studies conducted during the 1990s indicated an increase in the prevalence of symptoms of asthma; more recent investigations suggest that the trend is stabilizing or may even be reversing. OBJECTIVE. We compared 2 cross-sectional surveys conducted in 1994 and 2002 in 8 areas in northern and central Italy, to evaluate prevalence changes for asthma, allergic rhinitis, and eczema. METHODS. The International Study of Asthma and Allergies in Childhood methods and questionnaires were used to investigate 6- to 7-year-old children (16 115 and 11 287 questionnaires completed by parents in 1994-1995 and 2002, respectively) and 13- to 14-year-old adolescents (19 723 and 10 267 questionnaires completed by adolescents in 1994-1995 and 2002, respectively). In each phase, the overall response rate was > 90%. Prevalence changes were calculated as the absolute difference between the prevalence recorded on the 2 occasions. RESULTS. The prevalence of wheeze (past 12 months) increased slightly among children (change: 0.8%; 95% confidence interval [CI]: 0.0% to 1.6%) and was rather stable among adolescents. Symptoms of allergic rhinitis (children: change: 5.2%; 95% CI: 4.0% to 6.4%; adolescents: change: 4.1%; 95% CI: 1.9% to 6.3%) and symptoms of atopic eczema ( children: change: 4.4%; 95% CI: 3.6% to 5.2%; adolescents: change: 2.1%; 95% CI: 1.2% to 3.0%) increased clearly in both age groups. There was some heterogeneity across the centers among adolescents, especially for allergic rhinitis, with larger increases seen in the 3 metropolitan areas. The changes observed paralleled profound family changes, ie, better parental education, higher rates of maternal employment, and lower rates of exposure to parental smoke. These factors, however, do not explain all of the observed changes in prevalence. CONCLUSIONS. The results indicate that the epidemiologic features of asthma and allergies in Italy are changing rapidly, although the causes are still uncertain.. asthma| rhinitis| eczema| children| adolescents|increasing prevalence| hay-fever| symptoms| schoolchildren| rhinitis| germany| eczema| trends| isaac| sensitization.	JAN-2006	asthma| rhinitis| eczema| children| adolescents|increasing prevalence| hay-fever| symptoms| schoolchildren| rhinitis| germany| eczema| trends| isaac| sensitization	Galassi, C; De Sario, M; Biggeri, A; Bisanti, L; Chellini, E; Ciccone, G; Petronio, MG; Piffer, S; Sestini, P; Rusconi, F; Viegi, G; Forastiere, F	Changes in prevalence of asthma and allergies among children and adolescents in Italy: 1994-2002		PEDIATRICS	asthma; rhinitis; eczema; children; adolescents	INCREASING PREVALENCE; HAY-FEVER; SYMPTOMS; SCHOOLCHILDREN; RHINITIS; GERMANY; ECZEMA; TRENDS; ISAAC; SENSITIZATION	BACKGROUND. Several studies conducted during the 1990s indicated an increase in the prevalence of symptoms of asthma; more recent investigations suggest that the trend is stabilizing or may even be reversing. OBJECTIVE. We compared 2 cross-sectional surveys conducted in 1994 and 2002 in 8 areas in northern and central Italy, to evaluate prevalence changes for asthma, allergic rhinitis, and eczema. METHODS. The International Study of Asthma and Allergies in Childhood methods and questionnaires were used to investigate 6- to 7-year-old children (16 115 and 11 287 questionnaires completed by parents in 1994-1995 and 2002, respectively) and 13- to 14-year-old adolescents (19 723 and 10 267 questionnaires completed by adolescents in 1994-1995 and 2002, respectively). In each phase, the overall response rate was > 90%. Prevalence changes were calculated as the absolute difference between the prevalence recorded on the 2 occasions. RESULTS. The prevalence of wheeze (past 12 months) increased slightly among children (change: 0.8%; 95% confidence interval [CI]: 0.0% to 1.6%) and was rather stable among adolescents. Symptoms of allergic rhinitis (children: change: 5.2%; 95% CI: 4.0% to 6.4%; adolescents: change: 4.1%; 95% CI: 1.9% to 6.3%) and symptoms of atopic eczema ( children: change: 4.4%; 95% CI: 3.6% to 5.2%; adolescents: change: 2.1%; 95% CI: 1.2% to 3.0%) increased clearly in both age groups. There was some heterogeneity across the centers among adolescents, especially for allergic rhinitis, with larger increases seen in the 3 metropolitan areas. The changes observed paralleled profound family changes, ie, better parental education, higher rates of maternal employment, and lower rates of exposure to parental smoke. These factors, however, do not explain all of the observed changes in prevalence. CONCLUSIONS. The results indicate that the epidemiologic features of asthma and allergies in Italy are changing rapidly, although the causes are still uncertain.	26	100	2006	9	10.1542/peds.2004-2709	Pediatrics
Is the global rise of asthma an early impact of anthropogenic climate change?. The increase in asthma incidence, prevalence, and morbidity over recent decades presents a significant challenge to public health. Pollen is an important trigger of some types of asthma, and both pollen quantity and season depend on climatic and meteorologic variables. Over the same period as the global rise in asthma, there have been considerable increases in atmospheric carbon dioxide concentration and global average surface temperature. We hypothesize anthropogenic climate change as a plausible contributor to the rise in asthma. Greater concentrations of carbon dioxide and higher temperatures may increase pollen quantity and induce longer pollen seasons. Pollen allergenicity can also increase as a result of these changes in climate. Exposure in early life to a more allergenic environment may also provoke the development of other atopic conditions, such as eczema and allergic rhinitis. Although the etiology of asthma is complex, the recent global rise in asthma could be an early, health effect of anthropogenic climate change.. ragweed ambrosia-artemisiifolia| outdoor air-pollution| childhood asthma| environmental-factors| public-health| respiratory allergy| common ragweed| atopic eczema| prevalence| pollen.	AUG-2005	ragweed ambrosia-artemisiifolia| outdoor air-pollution| childhood asthma| environmental-factors| public-health| respiratory allergy| common ragweed| atopic eczema| prevalence| pollen	Beggs, PJ; Bambrick, HJ	Is the global rise of asthma an early impact of anthropogenic climate change?		ENVIRONMENTAL HEALTH PERSPECTIVES		RAGWEED AMBROSIA-ARTEMISIIFOLIA; OUTDOOR AIR-POLLUTION; CHILDHOOD ASTHMA; ENVIRONMENTAL-FACTORS; PUBLIC-HEALTH; RESPIRATORY ALLERGY; COMMON RAGWEED; ATOPIC ECZEMA; PREVALENCE; POLLEN	The increase in asthma incidence, prevalence, and morbidity over recent decades presents a significant challenge to public health. Pollen is an important trigger of some types of asthma, and both pollen quantity and season depend on climatic and meteorologic variables. Over the same period as the global rise in asthma, there have been considerable increases in atmospheric carbon dioxide concentration and global average surface temperature. We hypothesize anthropogenic climate change as a plausible contributor to the rise in asthma. Greater concentrations of carbon dioxide and higher temperatures may increase pollen quantity and induce longer pollen seasons. Pollen allergenicity can also increase as a result of these changes in climate. Exposure in early life to a more allergenic environment may also provoke the development of other atopic conditions, such as eczema and allergic rhinitis. Although the etiology of asthma is complex, the recent global rise in asthma could be an early, health effect of anthropogenic climate change.	66	100	2005	5	10.1289/ehp.7724	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Short-term effects of air pollution on daily asthma emergency room admissions. Many time-series studies have shown positive associations between air pollutants and asthma morbidity. However, few studies have included pollen as a potential confounder when examining this relationship. This study analysed the short-term association between air pollutants (sulphur dioxide (SO2), particles measured with a median aerodynamic diameter of <10 mum (PM10), nitrogen dioxide (NO2) and ozone (O-3)) and asthma emergency room admissions in Madrid, Spain, in 1995-1998, adjusting for four types of pollen with allergenic potential (Olea europaea, Plantago sp., Poaceae and Urticaceae). Data were analysed using autoregressive Poisson regression and generalised additive models (GAM). The strongest associations were observed at 1 day lag for O-3, and 3 days lag for the remaining pollutants. Using Poisson regression, a single-pollutant model showed that a 10-mug-m(-3) rise in pollutant level led to relative risks of: 1.039 for PM10; 1.029 for SO2; 1.033 for NO2; and 1.045 for O-3. Adjustment for the different types of pollen led to no substantial variation in these associations. In the multipollutant models for cold-season pollutants (including PM10, SO2 and the four types of pollen) and photochemical pollutants (including NO2, O-3 and the four types of pollen) the associations for PM10, NO2 and O-3 held, but no relationship with SO2 was evident. GAM analysis yielded the same results, both in terms of lags and of quantification of the effect for all pollutants. In conclusion, the usual air pollution levels in Madrid were associated with an increase in asthma emergency room admissions, and this association remained controlling for the presence of ambient pollen.. air pollution| asthma| emergency room admissions| pollen| time-series|hospital admissions| environmental-factors| childhood asthma| sulfur-dioxide| aphea project| mexico-city| visits| association| pollutants| mortality.	NOV-2003	air pollution| asthma| emergency room admissions| pollen| time-series|hospital admissions| environmental-factors| childhood asthma| sulfur-dioxide| aphea project| mexico-city| visits| association| pollutants| mortality	Galan, I; Tobias, A; Banegas, JR; Aranguez, E	Short-term effects of air pollution on daily asthma emergency room admissions		EUROPEAN RESPIRATORY JOURNAL	air pollution; asthma; emergency room admissions; pollen; time-series	HOSPITAL ADMISSIONS; ENVIRONMENTAL-FACTORS; CHILDHOOD ASTHMA; SULFUR-DIOXIDE; APHEA PROJECT; MEXICO-CITY; VISITS; ASSOCIATION; POLLUTANTS; MORTALITY	Many time-series studies have shown positive associations between air pollutants and asthma morbidity. However, few studies have included pollen as a potential confounder when examining this relationship. This study analysed the short-term association between air pollutants (sulphur dioxide (SO2), particles measured with a median aerodynamic diameter of <10 mum (PM10), nitrogen dioxide (NO2) and ozone (O-3)) and asthma emergency room admissions in Madrid, Spain, in 1995-1998, adjusting for four types of pollen with allergenic potential (Olea europaea, Plantago sp., Poaceae and Urticaceae). Data were analysed using autoregressive Poisson regression and generalised additive models (GAM). The strongest associations were observed at 1 day lag for O-3, and 3 days lag for the remaining pollutants. Using Poisson regression, a single-pollutant model showed that a 10-mug-m(-3) rise in pollutant level led to relative risks of: 1.039 for PM10; 1.029 for SO2; 1.033 for NO2; and 1.045 for O-3. Adjustment for the different types of pollen led to no substantial variation in these associations. In the multipollutant models for cold-season pollutants (including PM10, SO2 and the four types of pollen) and photochemical pollutants (including NO2, O-3 and the four types of pollen) the associations for PM10, NO2 and O-3 held, but no relationship with SO2 was evident. GAM analysis yielded the same results, both in terms of lags and of quantification of the effect for all pollutants. In conclusion, the usual air pollution levels in Madrid were associated with an increase in asthma emergency room admissions, and this association remained controlling for the presence of ambient pollen.	52	100	2003	7	10.1183/09031936.03.00013003	Respiratory System
IgG antibodies against microorganisms and atopic disease in Danish adults: The Copenhagen Allergy Study. Background: Seropositivity to food-borne and orofecal microorganisms (hepatitis A virus, Helicobacter pylori, and Toxoplasma gondii), which are considered to be markers of poor hygiene, has been reported to be associated with a lower prevalence of atopy. In contrast, colonization of the gut with Clostridium difficile, a potential intestinal bacterial pathogen, in early childhood may be associated with a higher prevalence of atopy. Objective: The objective of this study was to investigate the association between atopy and exposure to 2 groups of food-borne and orofecal microorganisms: (1) markers of a poor hygiene and (2) intestinal bacterial pathogens. Methods: A cross-sectional population-based study of 15- to 69-year-olds living in Copenhagen, Denmark, was carried out in 1990 to 1991. Atopy was defined as a positive test result for specific IgE to at least 1 of 6 inhalant allergens. Exposure to microorganisms was assessed as IgG seropositivity to microorganisms. Results: Seropositivity to 2 or 3 markers of poor hygiene (hepatitis A virus, H pylori, and T gondii) was associated with a lower prevalence of atopy (adjusted odds ratio, 0.5; 95% CI, 0.3 to 0.8). In contrast, seropositivity to 2 or 3 intestinal bacterial pathogens (C difficile, Campylobacter jejuni, and Yersinia enterocolitica) was associated with a higher prevalence of atopy (adjusted odds ratio, 1.7; 95% Cl, 1.2 to 2.6). Conclusion: Exposure to markers of poor hygiene was associated with a lower prevalence of atopy, whereas exposure to intestinal bacterial pathogens was associated with a higher prevalence of atopy. These findings raise the hypothesis that different groups of food-borne and orofecal microorganisms may have different effects on the risk of atopy.. allergic rhinitis| atopy| campylobacter jejuni| clostridium difficile| helicobacter pylori| hepatitis a virus| respiratory hypersensitivity| toxoplasma gondii|hepatitis-a| intestinal microflora| helicobacter-pylori| hygiene hypothesis| hay-fever| prevalence| infection| asthma| population| infants.	APR-2003	allergic rhinitis| atopy| campylobacter jejuni| clostridium difficile| helicobacter pylori| hepatitis a virus| respiratory hypersensitivity| toxoplasma gondii|hepatitis-a| intestinal microflora| helicobacter-pylori| hygiene hypothesis| hay-fever| prevalence| infection| asthma| population| infants	Linneberg, A; Ostergaard, C; Tvede, M; Andersen, LP; Nielsen, NH; Madsen, F; Frolund, L; Dirksen, A; Jorgensen, T	IgG antibodies against microorganisms and atopic disease in Danish adults: The Copenhagen Allergy Study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergic rhinitis; atopy; Campylobacter jejuni; Clostridium difficile; Helicobacter pylori; hepatitis A virus; respiratory hypersensitivity; Toxoplasma gondii	HEPATITIS-A; INTESTINAL MICROFLORA; HELICOBACTER-PYLORI; HYGIENE HYPOTHESIS; HAY-FEVER; PREVALENCE; INFECTION; ASTHMA; POPULATION; INFANTS	Background: Seropositivity to food-borne and orofecal microorganisms (hepatitis A virus, Helicobacter pylori, and Toxoplasma gondii), which are considered to be markers of poor hygiene, has been reported to be associated with a lower prevalence of atopy. In contrast, colonization of the gut with Clostridium difficile, a potential intestinal bacterial pathogen, in early childhood may be associated with a higher prevalence of atopy. Objective: The objective of this study was to investigate the association between atopy and exposure to 2 groups of food-borne and orofecal microorganisms: (1) markers of a poor hygiene and (2) intestinal bacterial pathogens. Methods: A cross-sectional population-based study of 15- to 69-year-olds living in Copenhagen, Denmark, was carried out in 1990 to 1991. Atopy was defined as a positive test result for specific IgE to at least 1 of 6 inhalant allergens. Exposure to microorganisms was assessed as IgG seropositivity to microorganisms. Results: Seropositivity to 2 or 3 markers of poor hygiene (hepatitis A virus, H pylori, and T gondii) was associated with a lower prevalence of atopy (adjusted odds ratio, 0.5; 95% CI, 0.3 to 0.8). In contrast, seropositivity to 2 or 3 intestinal bacterial pathogens (C difficile, Campylobacter jejuni, and Yersinia enterocolitica) was associated with a higher prevalence of atopy (adjusted odds ratio, 1.7; 95% Cl, 1.2 to 2.6). Conclusion: Exposure to markers of poor hygiene was associated with a lower prevalence of atopy, whereas exposure to intestinal bacterial pathogens was associated with a higher prevalence of atopy. These findings raise the hypothesis that different groups of food-borne and orofecal microorganisms may have different effects on the risk of atopy.	34	100	2003	7	10.1067/mai.2003.1335	Allergy; Immunology
Family history as a predictor of asthma risk. Background: Asthma, one of the most important chronic diseases of children, disproportionately affects minority and low-income children. Many environmental risk factors for asthma have been identified, including animal, mite, and other allergens; cigarette smoke; and air pollutants. Genetics also play an important causative role, as indicated by familial aggregation and the identification of candidate genes and chromosomal regions linked to asthma risk. Using a positive family history of asthma to identify children at increased risk could provide a basis for targeted prevention efforts, aimed at reducing exposure to environmental risk factors. Methods: To assess the predictive value of family history as an indicator of risk for childhood asthma, we reviewed population-based studies that evaluated family history of asthma and atopic disease in children with asthma. Results: Our search identified 33 studies from all geographic regions of the world for review. The studies varied in definitions of positive family history and asthma phenotype and used study populations with asthma prevalence ranging from 2% to 26%. Nevertheless, family history of asthma in one or more first-degree relatives was consistently identified as a risk factor for asthma. In ten studies, sensitivity and predictive value of a positive family history of asthma could be calculated: sensitivity ranged from 4% to 43%, positive predictive value from 11% to 37%, and negative predictive value from 86% to 97%. Conclusion: Although a positive family history predicts an increased risk of asthma, it identifies a minority of children at risk. Positive family history may have utility in targeting some individual prevention efforts, but the low positive predictive value limits its value as a means to direct environmental remediation efforts.. primary-school children| childhood asthma| allergic diseases| airway hyperresponsiveness| bronchial-asthma| parental smoking| young-children| prevalence| symptoms| atopy.	FEB-2003	primary-school children| childhood asthma| allergic diseases| airway hyperresponsiveness| bronchial-asthma| parental smoking| young-children| prevalence| symptoms| atopy	Burke, W; Fesinmeyer, M; Reed, K; Hampson, L; Carlsten, C	Family history as a predictor of asthma risk		AMERICAN JOURNAL OF PREVENTIVE MEDICINE		PRIMARY-SCHOOL CHILDREN; CHILDHOOD ASTHMA; ALLERGIC DISEASES; AIRWAY HYPERRESPONSIVENESS; BRONCHIAL-ASTHMA; PARENTAL SMOKING; YOUNG-CHILDREN; PREVALENCE; SYMPTOMS; ATOPY	Background: Asthma, one of the most important chronic diseases of children, disproportionately affects minority and low-income children. Many environmental risk factors for asthma have been identified, including animal, mite, and other allergens; cigarette smoke; and air pollutants. Genetics also play an important causative role, as indicated by familial aggregation and the identification of candidate genes and chromosomal regions linked to asthma risk. Using a positive family history of asthma to identify children at increased risk could provide a basis for targeted prevention efforts, aimed at reducing exposure to environmental risk factors. Methods: To assess the predictive value of family history as an indicator of risk for childhood asthma, we reviewed population-based studies that evaluated family history of asthma and atopic disease in children with asthma. Results: Our search identified 33 studies from all geographic regions of the world for review. The studies varied in definitions of positive family history and asthma phenotype and used study populations with asthma prevalence ranging from 2% to 26%. Nevertheless, family history of asthma in one or more first-degree relatives was consistently identified as a risk factor for asthma. In ten studies, sensitivity and predictive value of a positive family history of asthma could be calculated: sensitivity ranged from 4% to 43%, positive predictive value from 11% to 37%, and negative predictive value from 86% to 97%. Conclusion: Although a positive family history predicts an increased risk of asthma, it identifies a minority of children at risk. Positive family history may have utility in targeting some individual prevention efforts, but the low positive predictive value limits its value as a means to direct environmental remediation efforts.	67	100	2003	10	10.1016/S0749-3797(02)00589-5	Public, Environmental & Occupational Health; General & Internal Medicine
Analysis of expired air for oxidation products. Chronic inflammation is a critical feature of chronic obstructive pulmonary disease, cystic fibrosis, and asthma. This inflammation is associated with the increased production of reactive oxygen species or oxidative stress in the lungs. Oxidative stress may have several adverse effects and may amplify the inflammatory process; however, monitoring oxidative stress is difficult and may not be reflected by changes in blood markers. We have therefore developed several noninvasive markers in the exhaled breath that may indicate oxidative stress in the lungs, and we studied these in relationship to the severity of chronic inflammatory lung diseases. We analyzed the exhaled breath for the content of nitric oxide as a marker of inflammation, carbon monoxide as a marker of oxidative stress, and ethane, which is one of the end products of lipid peroxidation. In addition, we measured the concentration of markers of oxidative stress such as isoprostanes in exhaled breath condensate. Our results confirm that there are increased inflammation, oxidative stress, and lipid peroxidation in lung disease, as shown by elevated levels of nitric oxide, carbon monoxide, and ethane, respectively. The finding of lower levels of these gases in patients on steroid treatment and of higher levels in those with more severe lung disease, as assessed by lung function tests and clinical symptoms, reinforces the hypothesis that the noninvasive measurement of exhaled gases maybe useful in monitoring the underlying pathologic pathways of lung disease. Longitudinal studies are required to assess the clinical usefulness of these measurements in the monitoring of chronic inflammatory lung disease.. oxidative stress| noninvasive assessment|exhaled carbon-monoxide| obstructive pulmonary-disease| smooth-muscle cells| messenger-rna expression| nitric-oxide| cystic-fibrosis| lipid-peroxidation| asthmatic-patients| heme oxygenase-1| breath condensate.	DEC 15-2002	oxidative stress| noninvasive assessment|exhaled carbon-monoxide| obstructive pulmonary-disease| smooth-muscle cells| messenger-rna expression| nitric-oxide| cystic-fibrosis| lipid-peroxidation| asthmatic-patients| heme oxygenase-1| breath condensate	Paredi, P; Kharitonov, SA; Barnes, PJ	Analysis of expired air for oxidation products		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	oxidative stress; noninvasive assessment	EXHALED CARBON-MONOXIDE; OBSTRUCTIVE PULMONARY-DISEASE; SMOOTH-MUSCLE CELLS; MESSENGER-RNA EXPRESSION; NITRIC-OXIDE; CYSTIC-FIBROSIS; LIPID-PEROXIDATION; ASTHMATIC-PATIENTS; HEME OXYGENASE-1; BREATH CONDENSATE	Chronic inflammation is a critical feature of chronic obstructive pulmonary disease, cystic fibrosis, and asthma. This inflammation is associated with the increased production of reactive oxygen species or oxidative stress in the lungs. Oxidative stress may have several adverse effects and may amplify the inflammatory process; however, monitoring oxidative stress is difficult and may not be reflected by changes in blood markers. We have therefore developed several noninvasive markers in the exhaled breath that may indicate oxidative stress in the lungs, and we studied these in relationship to the severity of chronic inflammatory lung diseases. We analyzed the exhaled breath for the content of nitric oxide as a marker of inflammation, carbon monoxide as a marker of oxidative stress, and ethane, which is one of the end products of lipid peroxidation. In addition, we measured the concentration of markers of oxidative stress such as isoprostanes in exhaled breath condensate. Our results confirm that there are increased inflammation, oxidative stress, and lipid peroxidation in lung disease, as shown by elevated levels of nitric oxide, carbon monoxide, and ethane, respectively. The finding of lower levels of these gases in patients on steroid treatment and of higher levels in those with more severe lung disease, as assessed by lung function tests and clinical symptoms, reinforces the hypothesis that the noninvasive measurement of exhaled gases maybe useful in monitoring the underlying pathologic pathways of lung disease. Longitudinal studies are required to assess the clinical usefulness of these measurements in the monitoring of chronic inflammatory lung disease.	51	100	2002	7	10.1164/rccm.2206012	General & Internal Medicine; Respiratory System
Present status on the genetic studies of asthma. Asthma, one of the most common chronic diseases, is a complex and heterogeneous disorder. The results of genome screens for asthma-related traits in 11 different populations identified at least 18 regions of the genome that probably house asthma/atopy genes. The most consistently replicated regions are on chromosomes 2% 5q, 6p, 12q and 13q. Positional cloning projects are ongoing in laboratories around the world to identify the asthma susceptibility loci in these regions. In addition, many candidate genes have been associated with asthma phenotypes, such as the genes in the IL-4/IL-13 pathway.. receptor-alpha-chain| quantitative-trait loci| serum ige levels| genome-wide search| interleukin-4 receptor| atopic asthma| il-4 receptor| coding region| airway hyperresponsiveness| promoter polymorphisms.	DEC-2002	receptor-alpha-chain| quantitative-trait loci| serum ige levels| genome-wide search| interleukin-4 receptor| atopic asthma| il-4 receptor| coding region| airway hyperresponsiveness| promoter polymorphisms	Hoffjan, S; Ober, C	Present status on the genetic studies of asthma		CURRENT OPINION IN IMMUNOLOGY		RECEPTOR-ALPHA-CHAIN; QUANTITATIVE-TRAIT LOCI; SERUM IGE LEVELS; GENOME-WIDE SEARCH; INTERLEUKIN-4 RECEPTOR; ATOPIC ASTHMA; IL-4 RECEPTOR; CODING REGION; AIRWAY HYPERRESPONSIVENESS; PROMOTER POLYMORPHISMS	Asthma, one of the most common chronic diseases, is a complex and heterogeneous disorder. The results of genome screens for asthma-related traits in 11 different populations identified at least 18 regions of the genome that probably house asthma/atopy genes. The most consistently replicated regions are on chromosomes 2% 5q, 6p, 12q and 13q. Positional cloning projects are ongoing in laboratories around the world to identify the asthma susceptibility loci in these regions. In addition, many candidate genes have been associated with asthma phenotypes, such as the genes in the IL-4/IL-13 pathway.	83	100	2002	9	10.1016/S0952-7915(02)00393-X	Immunology
Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells. A critical first-line antioxidant defense on the airway epithelial surface against reactive oxygen and nitrogen species (ROS and RNS) is extracellular glutathione peroxidase (eGPx). Little is known about the regulation of eGPx or its role in ROS-mediated lung diseases such as asthma. Here we show that eGPx is increased in the asthmatic airway in comparison to healthy controls. Higher levels of eGPx mRNA in asthmatic airway epithelium verified bronchial epithelial cells as the source for the increased eGPx, The eGPx mRNA in bronchial epithelial cells in vitro increased eightfold after exposure to ROS and glutathione, an essential cofactor for eGPx activity. Alterations in intracellular and extracellular oxidized and reduced glutathione were temporally associated with eGPx induction, further supporting redox mechanisms in gene expression, Overexpression of superoxide dismutase, but not catalase, inhibited induction and identified superoxide as a key intermediary. The eGPx mRNA half-life was not affected by ROS, suggesting a transcriptional mechanism for eGPx regulation. Fusion genes of deletion fragments of the eGPx gene 5' flanking region driving a reporter gene conclusively identified the ROS-responsive region, which contained the consensus DNA binding site for the redox-regulated transcription factor, activator protein 1.. reactive oxygen species| asthma| lung| nitrotyrosine|nitric-oxide synthase| plasma glutathione| superoxide-dismutase| exhaled air| gene| antioxidant| oxidation| peroxynitrite| inflammation| sequence.	JAN-2001	reactive oxygen species| asthma| lung| nitrotyrosine|nitric-oxide synthase| plasma glutathione| superoxide-dismutase| exhaled air| gene| antioxidant| oxidation| peroxynitrite| inflammation| sequence	Comhair, SAA; Bhathena, PR; Farver, C; Thunnissen, FBJM; Erzurum, SC	Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells		FASEB JOURNAL	reactive oxygen species; asthma; lung; nitrotyrosine	NITRIC-OXIDE SYNTHASE; PLASMA GLUTATHIONE; SUPEROXIDE-DISMUTASE; EXHALED AIR; GENE; ANTIOXIDANT; OXIDATION; PEROXYNITRITE; INFLAMMATION; SEQUENCE	A critical first-line antioxidant defense on the airway epithelial surface against reactive oxygen and nitrogen species (ROS and RNS) is extracellular glutathione peroxidase (eGPx). Little is known about the regulation of eGPx or its role in ROS-mediated lung diseases such as asthma. Here we show that eGPx is increased in the asthmatic airway in comparison to healthy controls. Higher levels of eGPx mRNA in asthmatic airway epithelium verified bronchial epithelial cells as the source for the increased eGPx, The eGPx mRNA in bronchial epithelial cells in vitro increased eightfold after exposure to ROS and glutathione, an essential cofactor for eGPx activity. Alterations in intracellular and extracellular oxidized and reduced glutathione were temporally associated with eGPx induction, further supporting redox mechanisms in gene expression, Overexpression of superoxide dismutase, but not catalase, inhibited induction and identified superoxide as a key intermediary. The eGPx mRNA half-life was not affected by ROS, suggesting a transcriptional mechanism for eGPx regulation. Fusion genes of deletion fragments of the eGPx gene 5' flanking region driving a reporter gene conclusively identified the ROS-responsive region, which contained the consensus DNA binding site for the redox-regulated transcription factor, activator protein 1.	51	100	2001	9	10.1096/fj.00-0085com	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology
Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma. Patients with glucocorticoid (CC)-dependent asthma present an ongoing inflammation of the airways despite chronic long-term treatment with oral GC. Interleukin (IL)-8 and granulocyte/macrophage colony-stimulating factor (GM-CSF) have been implicated in airway inflammation in severe asthma and their synthesis is normally repressed by GC. To further characterize the inflammatory process in GC-dependent asthma, we measured the release of IL-8 and CM-CSF by peripheral blood mononuclear cells (PBMC) of eight normal subjects, six untreated controlled asthmatics, six untreated uncontrolled asthmatics, and nine CC-dependent asthmatics. We show that PBMC from CC-dependent asthmatics released high amounts of these cytokines despite chronic in vivo exposure to CC (p < 0.001 versus normal subjects). In contrast, when untreated uncontrolled asthmatics were given a short course of oral CC, IL-8 and CM-CSF production was inhibited (p = 0.0078). Release of IL-8 and GM-CSF by PBMC of CC-dependent asthmatics was reduced after in vitro GC treatment (p < 0.002). We investigated whether the incapacity of CC to inhibit production of these cytokines in vivo was the result of a dysregulation of the glucocorticoid receptor (GR) in CC-dependent asthma. GR alpha and GR beta are, respectively, the functional receptor and a putative dominant negative form of the receptor. Western blot and polymerase chain reaction (PCR) analyses indicated that GR alpha was expressed at similar level in all groups and was largely predominant over GR beta. Thus, persistent release of IL-8 and CM-CSF in CC-dependent asthma is not associated with low expression of GR alpha or overexpression of GR beta.. colony-stimulating factor| nf-kappa-b| bronchial-mucosa| transcription factors| human neutrophils| messenger-rna| expression| gene| inflammation| isoform.	JUL-2000	colony-stimulating factor| nf-kappa-b| bronchial-mucosa| transcription factors| human neutrophils| messenger-rna| expression| gene| inflammation| isoform	Gagliardo, R; Chanez, P; Vignola, AM; Bousquet, J; Vachier, I; Godard, P; Bonsignore, G; Demoly, P; Mathieu, M	Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		COLONY-STIMULATING FACTOR; NF-KAPPA-B; BRONCHIAL-MUCOSA; TRANSCRIPTION FACTORS; HUMAN NEUTROPHILS; MESSENGER-RNA; EXPRESSION; GENE; INFLAMMATION; ISOFORM	Patients with glucocorticoid (CC)-dependent asthma present an ongoing inflammation of the airways despite chronic long-term treatment with oral GC. Interleukin (IL)-8 and granulocyte/macrophage colony-stimulating factor (GM-CSF) have been implicated in airway inflammation in severe asthma and their synthesis is normally repressed by GC. To further characterize the inflammatory process in GC-dependent asthma, we measured the release of IL-8 and CM-CSF by peripheral blood mononuclear cells (PBMC) of eight normal subjects, six untreated controlled asthmatics, six untreated uncontrolled asthmatics, and nine CC-dependent asthmatics. We show that PBMC from CC-dependent asthmatics released high amounts of these cytokines despite chronic in vivo exposure to CC (p < 0.001 versus normal subjects). In contrast, when untreated uncontrolled asthmatics were given a short course of oral CC, IL-8 and CM-CSF production was inhibited (p = 0.0078). Release of IL-8 and GM-CSF by PBMC of CC-dependent asthmatics was reduced after in vitro GC treatment (p < 0.002). We investigated whether the incapacity of CC to inhibit production of these cytokines in vivo was the result of a dysregulation of the glucocorticoid receptor (GR) in CC-dependent asthma. GR alpha and GR beta are, respectively, the functional receptor and a putative dominant negative form of the receptor. Western blot and polymerase chain reaction (PCR) analyses indicated that GR alpha was expressed at similar level in all groups and was largely predominant over GR beta. Thus, persistent release of IL-8 and CM-CSF in CC-dependent asthma is not associated with low expression of GR alpha or overexpression of GR beta.	35	100	2000	7		General & Internal Medicine; Respiratory System
The impact of transportation control measures on emission reductions during the 2008 Olympic Games in Beijing, China. Traffic congestion and air pollution were two major challenges for the planners of the 2008 Olympic Games in Beijing. The Beijing municipal government implemented a package of temporary transportation control measures during the event. In this paper. we report the results of a recent research project that investigated the effects of these measures on urban motor vehicle emissions in Beijing. Bottom-up methodology has been used to develop grid-based emission inventories with micro-scale vehicle activities and speed-dependent emission factors. The urban traffic emissions of volatile organic compounds (VOC). carbon monoxide (CO), nitrogen oxides (NO(x)) and particulate matter with an aerodynamic diameter of 10 mu m or less (PM(10)) during the 2008 Olympics were reduced by 55.5%, 56.8%, 45.7% and 51.6%, respectively, as compared to the grid-based emission inventory before the Olympics. Emission intensity was derived from curbside air quality monitoring at the North 4th Ring Road site, located about 7 km from the National Stadium. Comparison between the emission intensity before and during the 2008 Olympics shows a reduction of 44.5% and 49.0% in daily CO and NO(x) emission from motor vehicles. The results suggest that reasonable traffic system improvement strategies along with vehicle technology improvements can contribute to controlling total motor vehicle emissions in Beijing after the Olympic Games. (C) 2009 Elsevier Ltd. All rights reserved.. olympic games| transportation control measures| emission inventory| beijing|urban air-quality| motor-vehicle growth| vehicular emissions| childhood asthma| pollution| area| road| models| busan| korea.	JAN-2010	olympic games| transportation control measures| emission inventory| beijing|urban air-quality| motor-vehicle growth| vehicular emissions| childhood asthma| pollution| area| road| models| busan| korea	Zhou, Y; Wu, Y; Yang, L; Fu, LX; He, KB; Wang, SX; Hao, JM; Chen, JC; Li, CY	The impact of transportation control measures on emission reductions during the 2008 Olympic Games in Beijing, China		ATMOSPHERIC ENVIRONMENT	Olympic Games; Transportation control measures; Emission inventory; Beijing	URBAN AIR-QUALITY; MOTOR-VEHICLE GROWTH; VEHICULAR EMISSIONS; CHILDHOOD ASTHMA; POLLUTION; AREA; ROAD; MODELS; BUSAN; KOREA	Traffic congestion and air pollution were two major challenges for the planners of the 2008 Olympic Games in Beijing. The Beijing municipal government implemented a package of temporary transportation control measures during the event. In this paper. we report the results of a recent research project that investigated the effects of these measures on urban motor vehicle emissions in Beijing. Bottom-up methodology has been used to develop grid-based emission inventories with micro-scale vehicle activities and speed-dependent emission factors. The urban traffic emissions of volatile organic compounds (VOC). carbon monoxide (CO), nitrogen oxides (NO(x)) and particulate matter with an aerodynamic diameter of 10 mu m or less (PM(10)) during the 2008 Olympics were reduced by 55.5%, 56.8%, 45.7% and 51.6%, respectively, as compared to the grid-based emission inventory before the Olympics. Emission intensity was derived from curbside air quality monitoring at the North 4th Ring Road site, located about 7 km from the National Stadium. Comparison between the emission intensity before and during the 2008 Olympics shows a reduction of 44.5% and 49.0% in daily CO and NO(x) emission from motor vehicles. The results suggest that reasonable traffic system improvement strategies along with vehicle technology improvements can contribute to controlling total motor vehicle emissions in Beijing after the Olympic Games. (C) 2009 Elsevier Ltd. All rights reserved.	33	99	2010	9	10.1016/j.atmosenv.2009.10.040	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways. Background: House dust mite (HDM) induces allergic asthma in sensitized individuals, although the mechanisms by which HDM is sensed and recognized by the airway mucosa, leading to dendritic cell (DC) recruitment, activation, and subsequent T(H)2-mediated responses, are unknown. Objective: We sought to define the pathways by which HDM activates respiratory epithelium to induce allergic airway responses. Methods: Using a human airway epithelial cell line (16HBE14o-), we studied secretion of the DC chemokine CCL20 after exposure to HDM or other allergens, investigated components of the HDM responsible for the induction of chemokine release, and examined activation of signaling pathways. Central findings were also confirmed in primary human bronchial cells. Results: We demonstrate that exposure of airway epithelium to HDM results in specific and rapid secretion of CCL20, a chemokine attractant for immature DCs. The induction of CCL20 secretion is dose and time dependent and quite specific to HDM because other allergens, such as ragweed pollen and cockroach antigen, fail to significantly induce CCL20 secretion. Induction of CCL20 secretion is not protease or Toll-like receptor 2/4 dependent but, interestingly, relies on beta-glucan moieties within the HDM extract, as evidenced by the ability of other beta-glucans to competitively inhibit its secretion and by the fact that disruption of these structures by treatment of HDM with beta-glucanase significantly reduces subsequent chemokine secretion. Conclusion: Taken together, our results describe a novel mechanism for specific pattern recognition of HDM-derived beta-glucan moieties, which initiates allergic airway inflammation and, through recruitment of DCs, might link innate pattern recognition at the airway surface with adaptive immune responses. (J Allergy Clin Immunol 2009;123:612-8.). asthma| allergy| house dust mite| epithelium| dendritic cell| chemokine| pattern recognition| innate immunity|t-cell responses| dermatophagoides-pteronyssinus| dendritic cells| receptor ccr6| atopic asthma| mouse lung| allergen| inflammation| endotoxin| ccl20.	MAR-2009	asthma| allergy| house dust mite| epithelium| dendritic cell| chemokine| pattern recognition| innate immunity|t-cell responses| dermatophagoides-pteronyssinus| dendritic cells| receptor ccr6| atopic asthma| mouse lung| allergen| inflammation| endotoxin| ccl20	Nathan, AT; Peterson, EA; Chakir, J; Wills-Karp, M	Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Asthma; allergy; house dust mite; epithelium; dendritic cell; chemokine; pattern recognition; innate immunity	T-CELL RESPONSES; DERMATOPHAGOIDES-PTERONYSSINUS; DENDRITIC CELLS; RECEPTOR CCR6; ATOPIC ASTHMA; MOUSE LUNG; ALLERGEN; INFLAMMATION; ENDOTOXIN; CCL20	Background: House dust mite (HDM) induces allergic asthma in sensitized individuals, although the mechanisms by which HDM is sensed and recognized by the airway mucosa, leading to dendritic cell (DC) recruitment, activation, and subsequent T(H)2-mediated responses, are unknown. Objective: We sought to define the pathways by which HDM activates respiratory epithelium to induce allergic airway responses. Methods: Using a human airway epithelial cell line (16HBE14o-), we studied secretion of the DC chemokine CCL20 after exposure to HDM or other allergens, investigated components of the HDM responsible for the induction of chemokine release, and examined activation of signaling pathways. Central findings were also confirmed in primary human bronchial cells. Results: We demonstrate that exposure of airway epithelium to HDM results in specific and rapid secretion of CCL20, a chemokine attractant for immature DCs. The induction of CCL20 secretion is dose and time dependent and quite specific to HDM because other allergens, such as ragweed pollen and cockroach antigen, fail to significantly induce CCL20 secretion. Induction of CCL20 secretion is not protease or Toll-like receptor 2/4 dependent but, interestingly, relies on beta-glucan moieties within the HDM extract, as evidenced by the ability of other beta-glucans to competitively inhibit its secretion and by the fact that disruption of these structures by treatment of HDM with beta-glucanase significantly reduces subsequent chemokine secretion. Conclusion: Taken together, our results describe a novel mechanism for specific pattern recognition of HDM-derived beta-glucan moieties, which initiates allergic airway inflammation and, through recruitment of DCs, might link innate pattern recognition at the airway surface with adaptive immune responses. (J Allergy Clin Immunol 2009;123:612-8.)	41	99	2009	7	10.1016/j.jaci.2008.12.006	Allergy; Immunology
Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery. Protease-activated receptor-2 (PAR-2) is known to be involved in epidermal permeability barrier function homeostasis. PAR-2 activation occurs after barrier disruption and further activation of PAR-2 by activating peptide significantly delays barrier recovery rate. Cockroach and house dust mite allergens, both known to be associated with the development of asthma, allergic rhinitis, and atopic dermatitis, have protease activity, which can activate PAR-2. In this study, we investigated the effects of both allergens on the epidermal barrier function as well as on the epidermal calcium gradient. Both allergens, when topically applied on the barrier-disrupted site, increased protease activities in the epidermis and delayed barrier recovery and lamellar body secretion in murine skin. The topical application of PAR-2-specific antagonist or protease inhibitors normalized the barrier recovery. Cockroach allergens induced intracellular calcium oscillations in cultured human keratinocytes through PAR-2-involved pathway, which was confirmed by desensitization protocol. Abnormal calcium ion distribution after barrier disruption was also observed in allergens-applied skin. These results suggest that allergens with protease activity can influence the epidermal permeability barrier homeostasis through PAR-2 activation and consequent modulation of the calcium ions in skin.. house-dust mites| atopy patch test| epithelial-cells| stratum-corneum| thrombin receptor| tight junctions| hairless mice| dermatitis| skin| association.	AUG-2008	house-dust mites| atopy patch test| epithelial-cells| stratum-corneum| thrombin receptor| tight junctions| hairless mice| dermatitis| skin| association	Jeon, SK; Kim, HJ; Youm, JK; Ahn, SK; Choi, EH; Sohn, MH; Kim, KE; Hong, JH; Shin, DM; Lee, SH	Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery		JOURNAL OF INVESTIGATIVE DERMATOLOGY		HOUSE-DUST MITES; ATOPY PATCH TEST; EPITHELIAL-CELLS; STRATUM-CORNEUM; THROMBIN RECEPTOR; TIGHT JUNCTIONS; HAIRLESS MICE; DERMATITIS; SKIN; ASSOCIATION	Protease-activated receptor-2 (PAR-2) is known to be involved in epidermal permeability barrier function homeostasis. PAR-2 activation occurs after barrier disruption and further activation of PAR-2 by activating peptide significantly delays barrier recovery rate. Cockroach and house dust mite allergens, both known to be associated with the development of asthma, allergic rhinitis, and atopic dermatitis, have protease activity, which can activate PAR-2. In this study, we investigated the effects of both allergens on the epidermal barrier function as well as on the epidermal calcium gradient. Both allergens, when topically applied on the barrier-disrupted site, increased protease activities in the epidermis and delayed barrier recovery and lamellar body secretion in murine skin. The topical application of PAR-2-specific antagonist or protease inhibitors normalized the barrier recovery. Cockroach allergens induced intracellular calcium oscillations in cultured human keratinocytes through PAR-2-involved pathway, which was confirmed by desensitization protocol. Abnormal calcium ion distribution after barrier disruption was also observed in allergens-applied skin. These results suggest that allergens with protease activity can influence the epidermal permeability barrier homeostasis through PAR-2 activation and consequent modulation of the calcium ions in skin.	43	99	2008	10	10.1038/jid.2008.13	Dermatology
Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren. BACKGROUND: The biological mechanisms involved in inflammatory response to air pollution are not dearly understood. OBJECTIVE: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS: We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (Fe(NO)), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. RESULTS: An increase of 17.5 mu g/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [95% confidence interval (CI), 1.01-1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98-1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00-1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter < 2.5 pm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 see (FEV(1)) (p = 0.048) and forced vital capacity (FVC) (p = 0.012) in asthmatic children and with FVC (p = 0.021) in nonasthmatic children. FeNO and FEV(1) were inversely associated (p = 0.005) in asthmatic children. CONCLUSIONS: Exposure to PM(2.5) resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.. air pollution| airway inflammation| asthma| epidemiology| lung function| schoolchildren|exhaled nitric-oxide| diesel exhaust particles| peak expiratory flow| asthmatic-children| particulate matter| antioxidant supplementation| respiratory health| breath condensate| pulmonary-function| childhood asthma.	JUN-2008	air pollution| airway inflammation| asthma| epidemiology| lung function| schoolchildren|exhaled nitric-oxide| diesel exhaust particles| peak expiratory flow| asthmatic-children| particulate matter| antioxidant supplementation| respiratory health| breath condensate| pulmonary-function| childhood asthma	Barraza-Villarreal, A; Sunyer, J; Hernandez-Cadena, L; Escamilla-Nunez, MC; Sienra-Monge, JJ; Ramirez-Aguilar, M; Cortez-Lugo, M; Holguin, F; Diaz-Sanchez, D; Olin, AC; Romieu, I	Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; airway inflammation; asthma; epidemiology; lung function; schoolchildren	EXHALED NITRIC-OXIDE; DIESEL EXHAUST PARTICLES; PEAK EXPIRATORY FLOW; ASTHMATIC-CHILDREN; PARTICULATE MATTER; ANTIOXIDANT SUPPLEMENTATION; RESPIRATORY HEALTH; BREATH CONDENSATE; PULMONARY-FUNCTION; CHILDHOOD ASTHMA	BACKGROUND: The biological mechanisms involved in inflammatory response to air pollution are not dearly understood. OBJECTIVE: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS: We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (Fe(NO)), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. RESULTS: An increase of 17.5 mu g/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [95% confidence interval (CI), 1.01-1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98-1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00-1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter < 2.5 pm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 see (FEV(1)) (p = 0.048) and forced vital capacity (FVC) (p = 0.012) in asthmatic children and with FVC (p = 0.021) in nonasthmatic children. FeNO and FEV(1) were inversely associated (p = 0.005) in asthmatic children. CONCLUSIONS: Exposure to PM(2.5) resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.	56	99	2008	7	10.1289/ehp.10926	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation. We identify the tumor necrosis factor receptor superfamily 25 (TNFRSF25)/TNFSF15 pair as critical trigger for allergic lung inflammation, which is a cardinal feature of asthma. TNFRSF25 (TNFR25) signals are required to exert T helper cell 2 (Th2) effector function in Th2-polarized CD4 cells and co-stimulate interleukin (IL)-13 production by glycosphingo-lipid-activated NKT cells. In vivo, antibody blockade of TNFSF15 (TL1A), which is the ligand for TNFR25, inhibits lung inflammation and production of Th2 cytokines such as IL-13, even when administered days after airway antigen exposure. Similarly, blockade of TNFR25 by a dominant-negative (DN) transgene, DN TNFR25, confers resistance to lung inflammation in mice. Allergic lung inflammation-resistant, NKT-deficient mice become susceptible upon adoptive transfer of wild-type NKT cells, but not after transfer of DN TNFR25 transgenic NKT cells. The TNFR25/TL1A pair appears to provide an early signal for Th2 cytokine production in the lung, and therefore may be a drug target in attempts to attenuate lung inflammation in asthmatics.. domain-containing receptor| cd4(+) t-cells| nf-kappa-b| induce airway hyperreactivity| death-domain| nkt cells| signal-transduction| human eosinophils| cutting edge| murine model.	MAY 12-2008	domain-containing receptor| cd4(+) t-cells| nf-kappa-b| induce airway hyperreactivity| death-domain| nkt cells| signal-transduction| human eosinophils| cutting edge| murine model	Fang, L; Adkins, B; Deyev, V; Podack, ER	Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation		JOURNAL OF EXPERIMENTAL MEDICINE		DOMAIN-CONTAINING RECEPTOR; CD4(+) T-CELLS; NF-KAPPA-B; INDUCE AIRWAY HYPERREACTIVITY; DEATH-DOMAIN; NKT CELLS; SIGNAL-TRANSDUCTION; HUMAN EOSINOPHILS; CUTTING EDGE; MURINE MODEL	We identify the tumor necrosis factor receptor superfamily 25 (TNFRSF25)/TNFSF15 pair as critical trigger for allergic lung inflammation, which is a cardinal feature of asthma. TNFRSF25 (TNFR25) signals are required to exert T helper cell 2 (Th2) effector function in Th2-polarized CD4 cells and co-stimulate interleukin (IL)-13 production by glycosphingo-lipid-activated NKT cells. In vivo, antibody blockade of TNFSF15 (TL1A), which is the ligand for TNFR25, inhibits lung inflammation and production of Th2 cytokines such as IL-13, even when administered days after airway antigen exposure. Similarly, blockade of TNFR25 by a dominant-negative (DN) transgene, DN TNFR25, confers resistance to lung inflammation in mice. Allergic lung inflammation-resistant, NKT-deficient mice become susceptible upon adoptive transfer of wild-type NKT cells, but not after transfer of DN TNFR25 transgenic NKT cells. The TNFR25/TL1A pair appears to provide an early signal for Th2 cytokine production in the lung, and therefore may be a drug target in attempts to attenuate lung inflammation in asthmatics.	41	99	2008	12	10.1084/jem.20072528	Immunology; Research & Experimental Medicine
Regulation of airway mucin gene expression. Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and air-ways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting air-ways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes.. mucus| transcription| lung| epigenetics| differentiation|growth-factor receptor| nf-kappa-b| necrosis-factor-alpha| bronchial epithelial-cells| obstructive pulmonary-disease| human respiratory-tract| in-vitro| neutrophil elastase| pseudomonas-aeruginosa| dna methylation.	2008	mucus| transcription| lung| epigenetics| differentiation|growth-factor receptor| nf-kappa-b| necrosis-factor-alpha| bronchial epithelial-cells| obstructive pulmonary-disease| human respiratory-tract| in-vitro| neutrophil elastase| pseudomonas-aeruginosa| dna methylation	Thai, P; Loukoianov, A; Wachi, S; Wu, R	Regulation of airway mucin gene expression		ANNUAL REVIEW OF PHYSIOLOGY	mucus; transcription; lung; epigenetics; differentiation	GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; BRONCHIAL EPITHELIAL-CELLS; OBSTRUCTIVE PULMONARY-DISEASE; HUMAN RESPIRATORY-TRACT; IN-VITRO; NEUTROPHIL ELASTASE; PSEUDOMONAS-AERUGINOSA; DNA METHYLATION	Mucins are important components that exert a variety of functions in cell-cell interaction, epidermal growth factor receptor signaling, and air-ways protection. In the conducting airways of the lungs, mucins are the major contributor to the viscoelastic property of mucous secretion, which is the major barrier to trapping inhaled microbial organism, particulates, and oxidative pollutants. The homeostasis of mucin production is an important feature in conducting air-ways for the maintenance of mucociliary function. Aberrant mucin secretion and accumulation in airway lumen are clinical hallmarks associated with various lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, emphysema, and lung cancer. Among 20 known mucin genes identified, 11 of them have been verified at either the mRNA and/or protein level in airways. The regulation of mucin genes is complicated, as are the mediators and signaling pathways. This review summarizes the current view on the mediators, the signaling pathways, and the transcriptional units that are involved in the regulation of airway mucin gene expression. In addition, we also point out essential features of epigenetic mechanisms for the regulation of these genes.	147	99	2008	25	10.1146/annurev.physiol.70.113006.100441	Physiology
Advancing a multilevel framework for epidemiologic research on asthma disparities. Our understanding of asthma epidemiology is growing increasingly complex. Asthma outcomes are clearly socially patterned, with asthma ranking as a leading cause of health disparities among minority and low socioeconomic groups. Yet, the increasing prevalence and marked disparities in asthma remain largely. unexplained by known risk factors. In the United States, asthma disproportionately affects nonwhite children living in urban areas and children living in poverty. Low socioeconomic status (SES), ethnic minority group status, and residence in an inner-city environment are closely intertwined in the United States, making it a challenge to fully disentangle the independent effects of each of these characteristics on asthma morbidity. In addition, studies show geographic variation in asthma outcomes across large cities and neighborhoods within cities that cannot be explained by economic factors alone. Although more limited data are available, studies in rural areas also suggest the stratification of risk based on SES and the proportion of minorities. Among low-SES areas, those with predominantly minority, segregated populations seem especially burdened. Marginalized populations of lower socioeconomic position are disproportionately exposed to irritants (eg, tobacco smoke), pollutants (eg, diesel-related particles), and indoor allergens (eg, cockroach and mouse allergen). Moreover, these marginalized individuals may also live in communities that are increasingly socially toxic, which, in turn, may be related to the increased experience of psychosocial stress that may influence asthma morbidity. Epidemiologic trends suggest that asthma may provide an excellent paradigm for understanding the role of community-level contextual factors in disease. Specifically, a multilevel approach that includes an ecological perspective may help to explain heterogeneities in asthma expression across socioeconomic and geographic boundaries that, to date, remain largely unexplained. Traditionally, asthma epidemiology has focused on individual-level risk factors and family factors. Far less attention has been given to the broader social context in which individuals live. A multilevel approach that explicitly recognizes the embedding of asthma within its biological, psycho-socioeconomic, environmental, and community contexts, is likely to provide a better understanding of asthma disparities at different stages in the life course. Is it simply asthma disparities or is it social disparities in asthma?. air pollution| asthma disparities| environmental justice| housing| indoor allergens| stress| tobacco smoke| violence|inner-city children| diesel exhaust particles| aromatic-hydrocarbon concentrations| air-pollution| hay-fever| cigarette-smoking| risk-factors| allergic sensitization| environmental exposure| socioeconomic-status.	NOV-2007	air pollution| asthma disparities| environmental justice| housing| indoor allergens| stress| tobacco smoke| violence|inner-city children| diesel exhaust particles| aromatic-hydrocarbon concentrations| air-pollution| hay-fever| cigarette-smoking| risk-factors| allergic sensitization| environmental exposure| socioeconomic-status	Wright, RJ; Subramanian, SV	Advancing a multilevel framework for epidemiologic research on asthma disparities		CHEST	air pollution; asthma disparities; environmental justice; housing; indoor allergens; stress; tobacco smoke; violence	INNER-CITY CHILDREN; DIESEL EXHAUST PARTICLES; AROMATIC-HYDROCARBON CONCENTRATIONS; AIR-POLLUTION; HAY-FEVER; CIGARETTE-SMOKING; RISK-FACTORS; ALLERGIC SENSITIZATION; ENVIRONMENTAL EXPOSURE; SOCIOECONOMIC-STATUS	Our understanding of asthma epidemiology is growing increasingly complex. Asthma outcomes are clearly socially patterned, with asthma ranking as a leading cause of health disparities among minority and low socioeconomic groups. Yet, the increasing prevalence and marked disparities in asthma remain largely. unexplained by known risk factors. In the United States, asthma disproportionately affects nonwhite children living in urban areas and children living in poverty. Low socioeconomic status (SES), ethnic minority group status, and residence in an inner-city environment are closely intertwined in the United States, making it a challenge to fully disentangle the independent effects of each of these characteristics on asthma morbidity. In addition, studies show geographic variation in asthma outcomes across large cities and neighborhoods within cities that cannot be explained by economic factors alone. Although more limited data are available, studies in rural areas also suggest the stratification of risk based on SES and the proportion of minorities. Among low-SES areas, those with predominantly minority, segregated populations seem especially burdened. Marginalized populations of lower socioeconomic position are disproportionately exposed to irritants (eg, tobacco smoke), pollutants (eg, diesel-related particles), and indoor allergens (eg, cockroach and mouse allergen). Moreover, these marginalized individuals may also live in communities that are increasingly socially toxic, which, in turn, may be related to the increased experience of psychosocial stress that may influence asthma morbidity. Epidemiologic trends suggest that asthma may provide an excellent paradigm for understanding the role of community-level contextual factors in disease. Specifically, a multilevel approach that includes an ecological perspective may help to explain heterogeneities in asthma expression across socioeconomic and geographic boundaries that, to date, remain largely unexplained. Traditionally, asthma epidemiology has focused on individual-level risk factors and family factors. Far less attention has been given to the broader social context in which individuals live. A multilevel approach that explicitly recognizes the embedding of asthma within its biological, psycho-socioeconomic, environmental, and community contexts, is likely to provide a better understanding of asthma disparities at different stages in the life course. Is it simply asthma disparities or is it social disparities in asthma?	141	99	2007	13	10.1378/chest.07-1904	General & Internal Medicine; Respiratory System
A mechanism-based binding model for the population pharmacokinetics and pharmacodynamics of omalizumab. Aim Omalizumab, a humanized IgG monoclonal antibody that binds to human immunoglobulin E (IgE), interrupts the allergic cascade in asthmatic patients. The aim was to compare simultaneously drug exposure and IgE biomarker responses in Japanese and White patient populations. Methods An instantaneous equilibrium drug-ligand binding and turnover population model was built from 202 Japanese patients. A posterior predictive evaluation for the steady-state distributions of omalizumab and IgE was then carried out against 531 White patients. Results The mean parameters estimated from the Japanese patients were as follows: omalizumab clearance 7.32 +/- 0.153 ml h(-1), IgE clearance 71.0 +/- 4.68 ml h(-1) and the difference between that for omalizumab and the complex 5.86 +/- 0.920 ml h(-1), the volume of distribution for omalizumab and IgE 5900 +/- 107 ml, and that for the complex 3630 +/- 223 ml, the rate of IgE production 30.3 +/- 2.04 mu g h(-1). Half-lives of IgG (23 days) and IgE (2.4 days) were close to previous reports. The dissociation constant for binding, 1.07 nM, was similar to in vitro values. Clearance and volume of distribution for omalizumab varied with bodyweight, whereas the clearance and rate of production of IgE were predicted accurately by baseline IgE. Overall, these covariates explained much of the interindividual variability. Conclusions The predictiveness of the Japanese model was confirmed by Monte-Carlo simulations for a White population, also providing evidence that the pharmacokinetics of omalizumab and IgE were similar in these two populations. Furthermore, the model enabled the estimation of not only omalizumab disposition parameters, but also the binding with and the rate of production, distribution and elimination of its target, IgE.. atopic asthma| binding model monoclonal antibody| ige| nonmem|anti-ige antibodies| monoclonal-antibody| gammae-antibodies| immunoglobulin-g| therapy| metabolism| disease| myeloma| rabbits.	MAY-2007	atopic asthma| binding model monoclonal antibody| ige| nonmem|anti-ige antibodies| monoclonal-antibody| gammae-antibodies| immunoglobulin-g| therapy| metabolism| disease| myeloma| rabbits	Hayashi, N; Tsukamoto, Y; Sallas, WM; Lowe, PJ	A mechanism-based binding model for the population pharmacokinetics and pharmacodynamics of omalizumab		BRITISH JOURNAL OF CLINICAL PHARMACOLOGY	atopic asthma; binding model monoclonal antibody; IgE; NONMEM	ANTI-IGE ANTIBODIES; MONOCLONAL-ANTIBODY; GAMMAE-ANTIBODIES; IMMUNOGLOBULIN-G; THERAPY; METABOLISM; DISEASE; MYELOMA; RABBITS	Aim Omalizumab, a humanized IgG monoclonal antibody that binds to human immunoglobulin E (IgE), interrupts the allergic cascade in asthmatic patients. The aim was to compare simultaneously drug exposure and IgE biomarker responses in Japanese and White patient populations. Methods An instantaneous equilibrium drug-ligand binding and turnover population model was built from 202 Japanese patients. A posterior predictive evaluation for the steady-state distributions of omalizumab and IgE was then carried out against 531 White patients. Results The mean parameters estimated from the Japanese patients were as follows: omalizumab clearance 7.32 +/- 0.153 ml h(-1), IgE clearance 71.0 +/- 4.68 ml h(-1) and the difference between that for omalizumab and the complex 5.86 +/- 0.920 ml h(-1), the volume of distribution for omalizumab and IgE 5900 +/- 107 ml, and that for the complex 3630 +/- 223 ml, the rate of IgE production 30.3 +/- 2.04 mu g h(-1). Half-lives of IgG (23 days) and IgE (2.4 days) were close to previous reports. The dissociation constant for binding, 1.07 nM, was similar to in vitro values. Clearance and volume of distribution for omalizumab varied with bodyweight, whereas the clearance and rate of production of IgE were predicted accurately by baseline IgE. Overall, these covariates explained much of the interindividual variability. Conclusions The predictiveness of the Japanese model was confirmed by Monte-Carlo simulations for a White population, also providing evidence that the pharmacokinetics of omalizumab and IgE were similar in these two populations. Furthermore, the model enabled the estimation of not only omalizumab disposition parameters, but also the binding with and the rate of production, distribution and elimination of its target, IgE.	31	99	2007	14	10.1111/j.1365-2125.2006.02803.x	Pharmacology & Pharmacy
Assessment of the U937 cell line for the detection of contact allergens. The human myeloid cell line U937 was evaluated as an in vitro test system to identify contact sensitizers in order to develop alternatives to animal tests for the cosmetic industry. Specific culture conditions (i.e., presence of interleukin-4, IL-4) were applied to obtain a dendritic cell-like phenotype. In the described test protocol, these cells were exposed to test chemicals and then analyzed by flow cytometry for CD86 expression and by quantitative real-time reverse transcriptase-polymerase chain reaction for IL-I beta and IL-8 gene expressions. Eight sensitizers, three non-sensitizers and five oxidative hair dye precursors were examined after 24-, 48- and 72-h exposure times. Test item-specific modulations of the chosen activation markers (CD86, IL-1 beta and IL-8) suggest that this U937 activation test could discriminate test items classified as contact sensitizers or non-sensitizers in the local lymph node assay in mice (LLNA). More specifically, a test item can be considered as a potential sensitizer when it significantly induced the upregulation of the expression of at least two markers. Using this approach, we could correctly evaluate the dendritic cell (DC) activation potential for 15 out of 16 tested chemicals. We conclude that the U937 activation test may represent an useful tool in a future in vitro test battery for predicting sensitizing properties of chemicals. (c) 2007 Elsevier Inc. All rights reserved.. cd86| il-1 beta| il-8| u937 cell line| in vitro sensitization test|lymph-node assay| surface-marker expression| generated dendritic cells| in-vitro model| costimulatory molecules| signaling pathways| chemical allergen| skin sensitizers| messenger-rna| cytokine.	APR 15-2007	cd86| il-1 beta| il-8| u937 cell line| in vitro sensitization test|lymph-node assay| surface-marker expression| generated dendritic cells| in-vitro model| costimulatory molecules| signaling pathways| chemical allergen| skin sensitizers| messenger-rna| cytokine	Python, F; Goebel, C; Aeby, P	Assessment of the U937 cell line for the detection of contact allergens		TOXICOLOGY AND APPLIED PHARMACOLOGY	CD86; IL-1 beta; IL-8; U937 cell line; In vitro sensitization test	LYMPH-NODE ASSAY; SURFACE-MARKER EXPRESSION; GENERATED DENDRITIC CELLS; IN-VITRO MODEL; COSTIMULATORY MOLECULES; SIGNALING PATHWAYS; CHEMICAL ALLERGEN; SKIN SENSITIZERS; MESSENGER-RNA; CYTOKINE	The human myeloid cell line U937 was evaluated as an in vitro test system to identify contact sensitizers in order to develop alternatives to animal tests for the cosmetic industry. Specific culture conditions (i.e., presence of interleukin-4, IL-4) were applied to obtain a dendritic cell-like phenotype. In the described test protocol, these cells were exposed to test chemicals and then analyzed by flow cytometry for CD86 expression and by quantitative real-time reverse transcriptase-polymerase chain reaction for IL-I beta and IL-8 gene expressions. Eight sensitizers, three non-sensitizers and five oxidative hair dye precursors were examined after 24-, 48- and 72-h exposure times. Test item-specific modulations of the chosen activation markers (CD86, IL-1 beta and IL-8) suggest that this U937 activation test could discriminate test items classified as contact sensitizers or non-sensitizers in the local lymph node assay in mice (LLNA). More specifically, a test item can be considered as a potential sensitizer when it significantly induced the upregulation of the expression of at least two markers. Using this approach, we could correctly evaluate the dendritic cell (DC) activation potential for 15 out of 16 tested chemicals. We conclude that the U937 activation test may represent an useful tool in a future in vitro test battery for predicting sensitizing properties of chemicals. (c) 2007 Elsevier Inc. All rights reserved.	48	99	2007	12	10.1016/j.taap.2006.12.026	Pharmacology & Pharmacy; Toxicology
Prevention of allergic disease during childhood by allergen avoidance: The Isle of Wight prevention study. Background: Early life allergen exposure may increase the risk of childhood allergy, but the protective effect of reduction in allergen exposure remains uncertain. Objective: To evaluate the effect of reduction in food and house dust mite (HDM) allergen exposure in infancy in preventing asthma and allergy. Methods: Infants, at higher risk because of family predisposition, were recruited prenatally and randomized to prophylactic (n = 58) and control (n = 62) groups. Prophylactic group infants were either breast-fed with mother on a low allergen diet or given an extensively hydrolyzed formula. Exposure to HDM was reduced by the use of an acaricide and mattress covers. The control group followed standard advice. Development of allergic diseases and sensitization to common allergens (atopy) was assessed blindly at ages 1, 2, 4, and 8 years in all 120 children. Results: Repeated measurement analysis, adjusted for all relevant confounding variables, confirmed a preventive effect on asthma: adjusted odds ratio (OR), 0.24; 95% CI, 0.09-0.66; P = .005; atopic dermatitis, OR, 0.23; Cl, 0.08-0.64; P = .005; rhinitis, OR, 0.42; CI, 0.19-0.92; P = .03; and atopy, OR, 0.13; Cl, 0.05-0.32; P < .001. The protective effect was primarily observed in the subgroup of children with persistent disease (symptoms at all visits) and in those with evidence of allergic sensitization. Conclusion: Allergic diseases can be reduced, for at least the first 8 years of life, by combined food and HDM allergen avoidance in infancy. Clinical implications: Strict food and HDM allergen avoidance should be considered for prevention of allergy in high-risk infants.. atopy| allergy| asthma| rhinitis| atopic dermatitis| food allergy| prevention| diet| house dust mite| randomized controlled trial|house-dust mite| birth-cohort| asthma| exposure| infancy| sensitization| risk| age| outcomes| atopy.	FEB-2007	atopy| allergy| asthma| rhinitis| atopic dermatitis| food allergy| prevention| diet| house dust mite| randomized controlled trial|house-dust mite| birth-cohort| asthma| exposure| infancy| sensitization| risk| age| outcomes| atopy	Arshad, SH; Bateman, B; Sadeghnejad, A; Gant, C; Matthews, SM	Prevention of allergic disease during childhood by allergen avoidance: The Isle of Wight prevention study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	atopy; allergy; asthma; rhinitis; atopic dermatitis; food allergy; prevention; diet; house dust mite; randomized controlled trial	HOUSE-DUST MITE; BIRTH-COHORT; ASTHMA; EXPOSURE; INFANCY; SENSITIZATION; RISK; AGE; OUTCOMES; ATOPY	Background: Early life allergen exposure may increase the risk of childhood allergy, but the protective effect of reduction in allergen exposure remains uncertain. Objective: To evaluate the effect of reduction in food and house dust mite (HDM) allergen exposure in infancy in preventing asthma and allergy. Methods: Infants, at higher risk because of family predisposition, were recruited prenatally and randomized to prophylactic (n = 58) and control (n = 62) groups. Prophylactic group infants were either breast-fed with mother on a low allergen diet or given an extensively hydrolyzed formula. Exposure to HDM was reduced by the use of an acaricide and mattress covers. The control group followed standard advice. Development of allergic diseases and sensitization to common allergens (atopy) was assessed blindly at ages 1, 2, 4, and 8 years in all 120 children. Results: Repeated measurement analysis, adjusted for all relevant confounding variables, confirmed a preventive effect on asthma: adjusted odds ratio (OR), 0.24; 95% CI, 0.09-0.66; P = .005; atopic dermatitis, OR, 0.23; Cl, 0.08-0.64; P = .005; rhinitis, OR, 0.42; CI, 0.19-0.92; P = .03; and atopy, OR, 0.13; Cl, 0.05-0.32; P < .001. The protective effect was primarily observed in the subgroup of children with persistent disease (symptoms at all visits) and in those with evidence of allergic sensitization. Conclusion: Allergic diseases can be reduced, for at least the first 8 years of life, by combined food and HDM allergen avoidance in infancy. Clinical implications: Strict food and HDM allergen avoidance should be considered for prevention of allergy in high-risk infants.	30	99	2007	7	10.1016/j.jaci.2006.12.621	Allergy; Immunology
Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study. Background: Both a functional promoter polymorphism in the gene encoding CD14 (C-260T) and exposure to endotoxin are believed to play key roles in modulating the immune response and expression of atopic disease. Objective: We aimed to evaluate the role of the CD14 C-260T polymorphism in a population of African descent and to test for interaction between this genotype and house dust endotoxin (HDE) exposure on atopic phenotypes. Methods: Asthmatic probands and their families were recruited as part of the Barbados Asthma Genetics Study. The C-260T polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were genotyped. Endotoxin was measured in house dust samples. Results: Using a Family-Based Association Test, the C-260T allele appeared to be protective against asthma (z = -2.444; P = .015) and asthma severity (z = -2.615; P = .009) under a recessive model. No significant associations were observed for the G-1461T and C-1721T markers both individually and in haplotypes. In a case-control analysis, the CD14 TT genotype was found to reduce risk of asthma compared with the CD 14 CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated with lower asthma severity scores (P < .002). The TT genotype might protect against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03-131.7), suggesting a gene-environment interaction. Conclusion: These data suggest that the CD14-260 polymorphism may play a role in controlling risk to atopic disease and underscore the importance of incorporating key environmental exposures into studies of genetic risk factors.. cd14| endotoxin| lps| asthma| allergy| atopy| asthma severity| ige| genetics| gene-environment interaction|circulating soluble cd14| inflammatory response| pulmonary-function| innate immunity| vital capacity| normal men| tests| association| populations| inhalation.	JUN-2005	cd14| endotoxin| lps| asthma| allergy| atopy| asthma severity| ige| genetics| gene-environment interaction|circulating soluble cd14| inflammatory response| pulmonary-function| innate immunity| vital capacity| normal men| tests| association| populations| inhalation	Zambelli-Weiner, A; Ehrlich, E; Stockton, ML; Grant, AV; Zhang, S; Levett, PN; Beaty, TH; Barnes, KC	Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	CD14; endotoxin; LPS; asthma; allergy; atopy; asthma severity; IgE; genetics; gene-environment interaction	CIRCULATING SOLUBLE CD14; INFLAMMATORY RESPONSE; PULMONARY-FUNCTION; INNATE IMMUNITY; VITAL CAPACITY; NORMAL MEN; TESTS; ASSOCIATION; POPULATIONS; INHALATION	Background: Both a functional promoter polymorphism in the gene encoding CD14 (C-260T) and exposure to endotoxin are believed to play key roles in modulating the immune response and expression of atopic disease. Objective: We aimed to evaluate the role of the CD14 C-260T polymorphism in a population of African descent and to test for interaction between this genotype and house dust endotoxin (HDE) exposure on atopic phenotypes. Methods: Asthmatic probands and their families were recruited as part of the Barbados Asthma Genetics Study. The C-260T polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were genotyped. Endotoxin was measured in house dust samples. Results: Using a Family-Based Association Test, the C-260T allele appeared to be protective against asthma (z = -2.444; P = .015) and asthma severity (z = -2.615; P = .009) under a recessive model. No significant associations were observed for the G-1461T and C-1721T markers both individually and in haplotypes. In a case-control analysis, the CD14 TT genotype was found to reduce risk of asthma compared with the CD 14 CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated with lower asthma severity scores (P < .002). The TT genotype might protect against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03-131.7), suggesting a gene-environment interaction. Conclusion: These data suggest that the CD14-260 polymorphism may play a role in controlling risk to atopic disease and underscore the importance of incorporating key environmental exposures into studies of genetic risk factors.	39	99	2005	7	10.1016/j.jaci.2005.03.001	Allergy; Immunology
The safety of sublingual-swallow immunotherapy: an analysis of published studies. Background As the main target of sublingual immunotherapy (SLIT) is to reduce at most the occurrence of adverse events (AE), safety represents a critical issue. This aspect deserves particular mention when a higher dose of allergen extract than traditional subcutaneous immunotherapy (SCIT) is required to be effective: that may be up to 500 times that employed for SCIT. Objective All published controlled studies concerning SLIT-swallow were analysed to evaluate AE rates. Methods Studies were subdivided in two groups: (i) studies using low allergen dose (LAD), i.e. ranging from 1 to 50 times the dose commonly administered with SCIT, and (ii) studies with high allergen dose (HAD), i.e. ranging from 50 to 500 times the dose administered with SCIT. Results Twenty-five studies were altogether analysed: 13 studies belonged to the low-dose group, 12 belonged to the high-dose group. We considered all patients with at least one AE. Local reactions were significantly more frequent in the LAD group than in the HAD group (P < 0.0001), while there was no difference in the rate of systemic reactions. Severe systemic reactions were never reported. Conclusion This study represents the first analysis of the safety of SLIT concerning the allergen dose employed in the treatment. There is evidence that AE occurrence is substantially not dose-dependent. This fact highlights two main clinical aspects: the elevated tolerability of SLIT in general and the safety of HAD regimen.. high allergen dose| low allergen dose| safety| sublingual immunotherapy|double-blind placebo| house-dust-mite| standardized 5-grass-pollen extract| local allergoid immunotherapy| randomized controlled-trial| parietaria-judaica extract| grass-pollen| seasonal rhinoconjunctivitis| pediatric-patients| children.	MAY-2005	high allergen dose| low allergen dose| safety| sublingual immunotherapy|double-blind placebo| house-dust-mite| standardized 5-grass-pollen extract| local allergoid immunotherapy| randomized controlled-trial| parietaria-judaica extract| grass-pollen| seasonal rhinoconjunctivitis| pediatric-patients| children	Gidaro, GB; Marcucci, F; Sensi, L; Incorvaia, C; Frati, F; Ciprandi, G	The safety of sublingual-swallow immunotherapy: an analysis of published studies		CLINICAL AND EXPERIMENTAL ALLERGY	high allergen dose; low allergen dose; safety; sublingual immunotherapy	DOUBLE-BLIND PLACEBO; HOUSE-DUST-MITE; STANDARDIZED 5-GRASS-POLLEN EXTRACT; LOCAL ALLERGOID IMMUNOTHERAPY; RANDOMIZED CONTROLLED-TRIAL; PARIETARIA-JUDAICA EXTRACT; GRASS-POLLEN; SEASONAL RHINOCONJUNCTIVITIS; PEDIATRIC-PATIENTS; CHILDREN	Background As the main target of sublingual immunotherapy (SLIT) is to reduce at most the occurrence of adverse events (AE), safety represents a critical issue. This aspect deserves particular mention when a higher dose of allergen extract than traditional subcutaneous immunotherapy (SCIT) is required to be effective: that may be up to 500 times that employed for SCIT. Objective All published controlled studies concerning SLIT-swallow were analysed to evaluate AE rates. Methods Studies were subdivided in two groups: (i) studies using low allergen dose (LAD), i.e. ranging from 1 to 50 times the dose commonly administered with SCIT, and (ii) studies with high allergen dose (HAD), i.e. ranging from 50 to 500 times the dose administered with SCIT. Results Twenty-five studies were altogether analysed: 13 studies belonged to the low-dose group, 12 belonged to the high-dose group. We considered all patients with at least one AE. Local reactions were significantly more frequent in the LAD group than in the HAD group (P < 0.0001), while there was no difference in the rate of systemic reactions. Severe systemic reactions were never reported. Conclusion This study represents the first analysis of the safety of SLIT concerning the allergen dose employed in the treatment. There is evidence that AE occurrence is substantially not dose-dependent. This fact highlights two main clinical aspects: the elevated tolerability of SLIT in general and the safety of HAD regimen.	45	99	2005	7	10.1111/j.1365-2222.2005.02240.x	Allergy; Immunology
Photocatalytic degradation of isothiazolin-3-ones in water and emulsion paints containing nanocrystalline TiO2 and ZnO catalysts. The photocatalytic degradation of isothiazolin-3-ones has been studied using the catalytically active TiO2 and ZnO and the inactive paint grade TiO2, under various illumination and chemical conditions. The reaction follows a pseudo-first-order kinetics. Three types of lamps have been used. The photocatalytic degradation is faster under UV lamp, when it is compared to reaction under suntest and fluorescent lamps. In the presence of oxygen and H2O2, the reaction proceeds faster than in air atmosphere. ZnO exhibits comparable activity with TiO2 and in some cases it was found to be even better than TiO2. The reaction was studied in aqueous suspensions as well as on gas-solid interfaces. The degradation of isothiazolin-3-ones in paint formulations was also studied. (C) 2003 Elsevier B.V. All rights reserved.. titanium dioxide| zinc oxide| photodegradation| isothiazolin-3-ones| heterogeneous photocatalysis| allergens|microbicidal 3-isothiazolone compounds| electrodes| films| photodegradation| dispersions| suspensions| temperature| irradiation| environment| pollutants.	MAR 18-2004	titanium dioxide| zinc oxide| photodegradation| isothiazolin-3-ones| heterogeneous photocatalysis| allergens|microbicidal 3-isothiazolone compounds| electrodes| films| photodegradation| dispersions| suspensions| temperature| irradiation| environment| pollutants	Kandavelu, V; Kastien, H; Thampi, KR	Photocatalytic degradation of isothiazolin-3-ones in water and emulsion paints containing nanocrystalline TiO2 and ZnO catalysts		APPLIED CATALYSIS B-ENVIRONMENTAL	titanium dioxide; zinc oxide; photodegradation; isothiazolin-3-ones; heterogeneous photocatalysis; allergens	MICROBICIDAL 3-ISOTHIAZOLONE COMPOUNDS; ELECTRODES; FILMS; PHOTODEGRADATION; DISPERSIONS; SUSPENSIONS; TEMPERATURE; IRRADIATION; ENVIRONMENT; POLLUTANTS	The photocatalytic degradation of isothiazolin-3-ones has been studied using the catalytically active TiO2 and ZnO and the inactive paint grade TiO2, under various illumination and chemical conditions. The reaction follows a pseudo-first-order kinetics. Three types of lamps have been used. The photocatalytic degradation is faster under UV lamp, when it is compared to reaction under suntest and fluorescent lamps. In the presence of oxygen and H2O2, the reaction proceeds faster than in air atmosphere. ZnO exhibits comparable activity with TiO2 and in some cases it was found to be even better than TiO2. The reaction was studied in aqueous suspensions as well as on gas-solid interfaces. The degradation of isothiazolin-3-ones in paint formulations was also studied. (C) 2003 Elsevier B.V. All rights reserved.	38	99	2004	11	10.1016/j.apcatb.2003.09.022	Chemistry; Engineering
Toll-like receptor 4 polymorphism and severity of atopy in asthmatics. Endotoxin exposure may have a protective effect against asthma and atopy. An Asp299Gly polymorphism in the Toll-like receptor 4 (TLR4) gene reduces responsiveness to endotoxin. This study determined the effect of TLR4 polymorphism on the risk and severity of asthma and atopy. In all, 336 UK Caucasian families with greater than or equal to2 affected sibs (physician's diagnosis of asthma and current medication use) and 179 Caucasians without asthma or a family history of asthma were genotyped using ARMS-PCR. No association of the TLR4 polymorphism was found with the risk of developing asthma, either in parent-affected sibling trios, or in case-control analyses (P>0.05). In the first affected asthmatic siblings, the atopy severity score (based on size and number of positive skin-prick tests and specific IgE) was higher in those with the Asp/Gly or Gly/Gly genotypes (mean 1.8, s.d. 1.1, n=39) compared to those with the Asp/Asp genotype (mean 1.2, s.d. 1.0, n=279) (P=0.003, t-test). No associations were found with total <LF>IgE, FEV1 % predicted, slope of FEV1 response to methacholine or asthma severity score (P>0.05). This study confirms the previously observed lack of association of TLR4 polymorphisms with asthma. In contrast, the findings suggest that genetically determined hyporesponsiveness to endotoxin may increase atopy severity.. asthma| atopy| toll-like receptor 4| polymorphism (genetics)|toll-like receptor-4| house-dust endotoxin| mutations| exposure| gene| sensitization| association| children| hygiene| risk.	JAN-2004	asthma| atopy| toll-like receptor 4| polymorphism (genetics)|toll-like receptor-4| house-dust endotoxin| mutations| exposure| gene| sensitization| association| children| hygiene| risk	Yang, IA; Barton, SJ; Rorke, S; Cakebread, JA; Keith, TP; Clough, JB; Holgate, ST; Holloway, JW	Toll-like receptor 4 polymorphism and severity of atopy in asthmatics		GENES AND IMMUNITY	asthma; atopy; Toll-like receptor 4; polymorphism (genetics)	TOLL-LIKE RECEPTOR-4; HOUSE-DUST ENDOTOXIN; MUTATIONS; EXPOSURE; GENE; SENSITIZATION; ASSOCIATION; CHILDREN; HYGIENE; RISK	Endotoxin exposure may have a protective effect against asthma and atopy. An Asp299Gly polymorphism in the Toll-like receptor 4 (TLR4) gene reduces responsiveness to endotoxin. This study determined the effect of TLR4 polymorphism on the risk and severity of asthma and atopy. In all, 336 UK Caucasian families with greater than or equal to2 affected sibs (physician's diagnosis of asthma and current medication use) and 179 Caucasians without asthma or a family history of asthma were genotyped using ARMS-PCR. No association of the TLR4 polymorphism was found with the risk of developing asthma, either in parent-affected sibling trios, or in case-control analyses (P>0.05). In the first affected asthmatic siblings, the atopy severity score (based on size and number of positive skin-prick tests and specific IgE) was higher in those with the Asp/Gly or Gly/Gly genotypes (mean 1.8, s.d. 1.1, n=39) compared to those with the Asp/Asp genotype (mean 1.2, s.d. 1.0, n=279) (P=0.003, t-test). No associations were found with total <LF>IgE, FEV1 % predicted, slope of FEV1 response to methacholine or asthma severity score (P>0.05). This study confirms the previously observed lack of association of TLR4 polymorphisms with asthma. In contrast, the findings suggest that genetically determined hyporesponsiveness to endotoxin may increase atopy severity.	22	99	2004	5	10.1038/sj.gene.6364037	Genetics & Heredity; Immunology
Children's lung function and antioxidant vitamin, fruit, juice, and vegetable intake. The authors investigated the relation between children's pulmonary function and intake of fruits, vegetables, juices, and vitamins A, C, and E by examining cross-sectional data from 2,566 children in the Children's Health Study collected during 1997-1998. Low total vitamin C intake (less than or equal to10th percentile) was associated with deficits in forced vital capacity for both boys and girls and with deficits in flows that were larger in girls (forced expiratory volume in 1 second (FEV1), -3.3%, 95% confidence interval (CI): -6.0, -0.5; forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75), -5.5%, 95% CI: -10.5, -0.3) compared with boys (FEV1, -2.3%, 95% CI: -4.8, 0.3; FEF25-75, -2.4%, 95% CI: -7.4, 2.8). Low dietary vitamin E intake was associated with lower FEF25-75 (boys: FEF25-75 , -8.9%, 95% CI: -14.2, -3.3; girls: FEF25-75 , -2.5%, 95% CI: -8.3, 3.7). Deficits in FEF25-75 were associated with low dietary vitamin A intake in girls (FEF25-75, -7.9%, 95% CI: -12.7, -2.8) and with low total vitamin A intake in boys with asthma (FEF25-75, -15.6%, 95% CI: -27.6, -1.6). Low intakes of orange and other fruit juices, which were the largest source of vitamin C, were associated with deficits in forced vital capacity and FEV1 in boys. In summary, lung function levels were lower in children with inadequate dietary antioxidant vitamin intake.. antioxidants| ascorbic acid| child| diet| respiratory function tests| vitamin a| vitamin e|southern california communities| food frequency questionnaire| pulmonary-function| general-population| air-pollution| dietary antioxidants| differing levels| asthma| obstruction| association.	SEP 15-2003	antioxidants| ascorbic acid| child| diet| respiratory function tests| vitamin a| vitamin e|southern california communities| food frequency questionnaire| pulmonary-function| general-population| air-pollution| dietary antioxidants| differing levels| asthma| obstruction| association	Gilliland, FD; Berhane, KT; Li, YF; Gauderman, WJ; McConnell, R; Peters, J	Children's lung function and antioxidant vitamin, fruit, juice, and vegetable intake		AMERICAN JOURNAL OF EPIDEMIOLOGY	antioxidants; ascorbic acid; child; diet; respiratory function tests; vitamin A; vitamin E	SOUTHERN CALIFORNIA COMMUNITIES; FOOD FREQUENCY QUESTIONNAIRE; PULMONARY-FUNCTION; GENERAL-POPULATION; AIR-POLLUTION; DIETARY ANTIOXIDANTS; DIFFERING LEVELS; ASTHMA; OBSTRUCTION; ASSOCIATION	The authors investigated the relation between children's pulmonary function and intake of fruits, vegetables, juices, and vitamins A, C, and E by examining cross-sectional data from 2,566 children in the Children's Health Study collected during 1997-1998. Low total vitamin C intake (less than or equal to10th percentile) was associated with deficits in forced vital capacity for both boys and girls and with deficits in flows that were larger in girls (forced expiratory volume in 1 second (FEV1), -3.3%, 95% confidence interval (CI): -6.0, -0.5; forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75), -5.5%, 95% CI: -10.5, -0.3) compared with boys (FEV1, -2.3%, 95% CI: -4.8, 0.3; FEF25-75, -2.4%, 95% CI: -7.4, 2.8). Low dietary vitamin E intake was associated with lower FEF25-75 (boys: FEF25-75 , -8.9%, 95% CI: -14.2, -3.3; girls: FEF25-75 , -2.5%, 95% CI: -8.3, 3.7). Deficits in FEF25-75 were associated with low dietary vitamin A intake in girls (FEF25-75, -7.9%, 95% CI: -12.7, -2.8) and with low total vitamin A intake in boys with asthma (FEF25-75, -15.6%, 95% CI: -27.6, -1.6). Low intakes of orange and other fruit juices, which were the largest source of vitamin C, were associated with deficits in forced vital capacity and FEV1 in boys. In summary, lung function levels were lower in children with inadequate dietary antioxidant vitamin intake.	41	99	2003	9	10.1093/aje/kwg181	Public, Environmental & Occupational Health
Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort. Introduction There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results. Objective To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study. Methods Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders. Results A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38). Conclusion Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.. allergens| allergy and immunology| animals| asthma| cats| child| dogs| domestic| endotoxins| prevention| primary|cat allergen| children| childhood| ownership| school| homes| life| symptoms| environment| prevalence.	SEP-2003	allergens| allergy and immunology| animals| asthma| cats| child| dogs| domestic| endotoxins| prevention| primary|cat allergen| children| childhood| ownership| school| homes| life| symptoms| environment| prevalence	Almqvist, C; Egmar, AC; Hedlin, G; Lundqvist, M; Nordvall, SL; Pershagen, G; Svartengren, M; van Hage-Hamsten, M; Wickman, M	Direct and indirect exposure to pets - risk of sensitization and asthma at 4 years in a birth cohort		CLINICAL AND EXPERIMENTAL ALLERGY	allergens; allergy and immunology; animals; asthma; cats; child; dogs; domestic; endotoxins; prevention; primary	CAT ALLERGEN; CHILDREN; CHILDHOOD; OWNERSHIP; SCHOOL; HOMES; LIFE; SYMPTOMS; ENVIRONMENT; PREVALENCE	Introduction There are conflicting data on the association between early exposure to pets and allergic diseases. Bias related to retrospective information on pet ownership has been addressed as a reason for distorted study results. Objective To elucidate how early exposure to cat and dog relates to IgE-sensitization and asthma in children at 2 and 4 years of age, in a prospective birth-cohort study. Methods Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors and symptoms of allergic disease at birth, one, two and four years of age. Dust samples collected from the mothers' beds at birth were analysed for Fel d 1 and Can f 1 in a subgroup of the cohort. Blood samples taken at four years from 2614 children were analysed for allergen-specific IgE to common airborne allergens. Risk associations were calculated with a multiple logistic regression model, with adjustment for potential confounders. Results A correlation was seen between allergen levels and reported exposure to cat and dog. Exposure to cat seemed to increase the risk of cat sensitization, OR (odds ratio) 1.44 (95% confidence interval 1.03-2.01), whereas dog exposure did not have any effect on dog sensitization, OR 1.16 (0.79-1.72). Dog ownership was related to a reduced risk of sensitization to other airborne allergens, OR 0.36 (0.15-0.83), and a similar tendency was seen for cat ownership OR 0.63 (0.37-1.07). Early dog ownership seemed to be associated with a lower risk of asthma, OR 0.50 (0.24-1.03), with no corresponding effect after cat ownership, OR 0.88 (0.56-1.38). Conclusion Early exposure to cat seems to increase the risk of sensitization to cat but not of asthma at 4 years of age. Dog ownership, on the other hand, appears to be associated with lowered risk of sensitization to airborne allergens and asthma. Both aetiological relationships and selection effects have to be considered in the interpretation of these findings.	33	99	2003	8	10.1046/j.1365-2222.2003.01764.x	Allergy; Immunology
Nickel, chromium and cobalt in consumer products: revisiting safe levels in the new millennium. The transition metals nickel (Ni), chromium (Cr) and cobalt (Co) are common causes of allergic contact dermatitis (ACD). Given the high frequency with which these allergens can be associated with hand eczema in those responsible for domestic work, it has been suggested that contamination of household consumer products with these metals may be of relevance to the causation/chronicity of hand dermatitis. Dose-response studies using 48 h occlusive patch test conditions in sensitized individuals show that greater than or equal to90% of sensitized patients fail to react below 1 p.p.m., even on irritated skin. Assessment under more realistic exposure conditions has shown that in the presence of irritants and/or following repeated exposures, such individuals rarely react to levels below 10 p.p.m. On the basis of this information, it was recommended a decade ago that household (and other consumer) products should not contain more than 5 p.p.m. of each of Ni, Cr or Co and that, for an even greater degree of protection, the ultimate target level should be 1 p.p.m. The data generated since the original recommendations were made serve to reinforce the validity of these recommendations. Indeed, it is our view that typically the level of each of these transition metals should not normally exceed 1 p.p.m. Then, where consumer products meet this guideline fully, modern quantitative risk assessment shows clearly that elicitation of ACD is highly improbable, and the chance of the induction of sensitization is even lower.. nickel| chromate| cobalt| thresholds| consumer products| elicitation|allergic contact-dermatitis| lymph-node assay| risk assessment| hand eczema| exposure| skin| sensitization| thresholds| reactivity| models.	JUL-2003	nickel| chromate| cobalt| thresholds| consumer products| elicitation|allergic contact-dermatitis| lymph-node assay| risk assessment| hand eczema| exposure| skin| sensitization| thresholds| reactivity| models	Basketter, DA; Angelini, G; Ingber, A; Kern, PS; Menne, T	Nickel, chromium and cobalt in consumer products: revisiting safe levels in the new millennium		CONTACT DERMATITIS	nickel; chromate; cobalt; thresholds; consumer products; elicitation	ALLERGIC CONTACT-DERMATITIS; LYMPH-NODE ASSAY; RISK ASSESSMENT; HAND ECZEMA; EXPOSURE; SKIN; SENSITIZATION; THRESHOLDS; REACTIVITY; MODELS	The transition metals nickel (Ni), chromium (Cr) and cobalt (Co) are common causes of allergic contact dermatitis (ACD). Given the high frequency with which these allergens can be associated with hand eczema in those responsible for domestic work, it has been suggested that contamination of household consumer products with these metals may be of relevance to the causation/chronicity of hand dermatitis. Dose-response studies using 48 h occlusive patch test conditions in sensitized individuals show that greater than or equal to90% of sensitized patients fail to react below 1 p.p.m., even on irritated skin. Assessment under more realistic exposure conditions has shown that in the presence of irritants and/or following repeated exposures, such individuals rarely react to levels below 10 p.p.m. On the basis of this information, it was recommended a decade ago that household (and other consumer) products should not contain more than 5 p.p.m. of each of Ni, Cr or Co and that, for an even greater degree of protection, the ultimate target level should be 1 p.p.m. The data generated since the original recommendations were made serve to reinforce the validity of these recommendations. Indeed, it is our view that typically the level of each of these transition metals should not normally exceed 1 p.p.m. Then, where consumer products meet this guideline fully, modern quantitative risk assessment shows clearly that elicitation of ACD is highly improbable, and the chance of the induction of sensitization is even lower.	37	99	2003	7	10.1111/j.0105-1873.2003.00149.x	Allergy; Dermatology
CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma. Background: We have previously demonstrated that CpG oligodeoxymicleotides (CpG-ODNs) protect against eosinophilia and airway hyperresponsiveness in marine models of allergen-induced asthma. Acute inflammation is hypothesized to induce chronic airway responses, but no previous studies have evaluated the effects of CpG-ODNs on allergen-induced airway remodeling. Because remodeling is thought to be responsible for many of the long-term adverse effects on asthmatic patients, we evaluated whether CpG-ODNs might similarly prevent these changes using a murine model of recurrent allergen exposure. Objective: The purpose of this study was to evaluate the effect of CpG-ODNs on chronic inflammatory changes and airway remodeling by using a marine model of chronic allergen-induced asthma. Methods: C57BL/6 mice were sensitized to ovalbumin (OVA) and subsequently exposed to nebulized OVA by means of inhalation 3 times weekly for 6 weeks. Some mice received CpG-ODNs by means of intraperitoneal injection at the time of sensitization. At the end of the exposure period, mice were evaluated for the development of airway inflammation, airway hyperresponsiveness, and airway remodeling. Results: OVA-sensitized mice exposed to recurrent airway challenge with OVA have chronic inflammation, persistent airway hyperresponsiveness, and evidence of airway remodeling, including subepithelial collagen deposition and goblet cell hyperplasia-metaplasia. These changes are significantly reduced in mice treated with CpG-ODNs. Interestingly, mice treated with CpG-ODNs exhibit increased levels of bronchoalveolar lavage transforming growth factor P, suggesting that regulatory T cells might be responsible for some of these protective effects. Conclusion: CpG-ODNs are effective not only in preventing acute inflammation but also appear to reduce markers of airway remodeling that develop after chronic allergen exposure.. asthma| murine| cpg oligodeoxynucleotides| airway remodeling| collagen| subepithelial fibrosis| transforming growth factor beta| regulatory t lymphocytes|subepithelial fibrosis| flow obstruction| bronchial-asthma| inflammation| responsiveness| cells| methacholine| generation| modulation| responses.	DEC-2002	asthma| murine| cpg oligodeoxynucleotides| airway remodeling| collagen| subepithelial fibrosis| transforming growth factor beta| regulatory t lymphocytes|subepithelial fibrosis| flow obstruction| bronchial-asthma| inflammation| responsiveness| cells| methacholine| generation| modulation| responses	Jain, VV; Kitagaki, K; Businga, T; Hussain, I; George, C; O'Shaughnessy, P; Kline, JN	CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; murine; CpG oligodeoxynucleotides; airway remodeling; collagen; subepithelial fibrosis; transforming growth factor beta; regulatory T lymphocytes	SUBEPITHELIAL FIBROSIS; FLOW OBSTRUCTION; BRONCHIAL-ASTHMA; INFLAMMATION; RESPONSIVENESS; CELLS; METHACHOLINE; GENERATION; MODULATION; RESPONSES	Background: We have previously demonstrated that CpG oligodeoxymicleotides (CpG-ODNs) protect against eosinophilia and airway hyperresponsiveness in marine models of allergen-induced asthma. Acute inflammation is hypothesized to induce chronic airway responses, but no previous studies have evaluated the effects of CpG-ODNs on allergen-induced airway remodeling. Because remodeling is thought to be responsible for many of the long-term adverse effects on asthmatic patients, we evaluated whether CpG-ODNs might similarly prevent these changes using a murine model of recurrent allergen exposure. Objective: The purpose of this study was to evaluate the effect of CpG-ODNs on chronic inflammatory changes and airway remodeling by using a marine model of chronic allergen-induced asthma. Methods: C57BL/6 mice were sensitized to ovalbumin (OVA) and subsequently exposed to nebulized OVA by means of inhalation 3 times weekly for 6 weeks. Some mice received CpG-ODNs by means of intraperitoneal injection at the time of sensitization. At the end of the exposure period, mice were evaluated for the development of airway inflammation, airway hyperresponsiveness, and airway remodeling. Results: OVA-sensitized mice exposed to recurrent airway challenge with OVA have chronic inflammation, persistent airway hyperresponsiveness, and evidence of airway remodeling, including subepithelial collagen deposition and goblet cell hyperplasia-metaplasia. These changes are significantly reduced in mice treated with CpG-ODNs. Interestingly, mice treated with CpG-ODNs exhibit increased levels of bronchoalveolar lavage transforming growth factor P, suggesting that regulatory T cells might be responsible for some of these protective effects. Conclusion: CpG-ODNs are effective not only in preventing acute inflammation but also appear to reduce markers of airway remodeling that develop after chronic allergen exposure.	33	99	2002	6	10.1067/mai.2002.129371	Allergy; Immunology
Farm residence and exposures and the risk of allergic diseases in New Zealand children. Background: Studies in Europe have reported a reduced prevalence of allergy in farmers children. We aimed to determine if there is a similar reduction in allergy among New Zealand farm children. Methods: Two hundred and ninety-three children participated (60%) aged 7-10 years, from selected schools in small towns and the surrounding rural area. Skin prick tests (SPT) to eight common allergens were performed. Parents completed questionnaires about allergic and infectious diseases, place of residence, exposure to animals, and diet, and they provided dust from the livingroom floor. Endotoxin was measured using an Limulus amoebocyte lysate (LAL) assay and Der p 1 using enzyme-linked immunoassay ( ELISA). Results: Current farm abode was found to increase the risk of having symptoms associated with allergy, but not SPT positivity. Independent inverse associations were found for early-life exposures: at least weekly consumption of yoghurt with hayfever (odds ratio (OR) = 0.3, 95% confidence intervals (CI) 0.1-0.7) and allergic rhinitis (OR = 0.3, 95% CI 0.2-0.7); any unpasteurized milk consumption with atopic eczema/dermatitis syndrome (AEDS) (OR = 0.2, 95% CI 0.1-0.8); cats inside or outside with hayfever (OR = 0.4, 95% CI 0.1-1. 0) and AEDS (OR = 0.4, 95% CI 0.2-0.8); dogs inside or outside with asthma (OR = 0.4, 95% CI 0.2-0.8); and pigs with SPT positivity (OR = 0.2, 95% CI 0.1-0.9). Conclusions: Despite finding a protective effect of early-life animal exposures, we found a greater prevalence of allergic disease on farms.. animals| allergic rhinitis| asthma| eczema| endotoxin| der p 1| farming| hayfever| probiotics| skin prick test| wheeze|hay-fever| asthma prevalence| early-childhood| sensitization| endotoxin| atopy| environment| community| urban| size.	DEC-2002	animals| allergic rhinitis| asthma| eczema| endotoxin| der p 1| farming| hayfever| probiotics| skin prick test| wheeze|hay-fever| asthma prevalence| early-childhood| sensitization| endotoxin| atopy| environment| community| urban| size	Wickens, K; Lane, JM; Fitzharris, P; Siebers, R; Riley, G; Douwes, J; Smith, T; Crane, J	Farm residence and exposures and the risk of allergic diseases in New Zealand children		ALLERGY	animals; allergic rhinitis; asthma; eczema; endotoxin; Der p 1; farming; hayfever; probiotics; skin prick test; wheeze	HAY-FEVER; ASTHMA PREVALENCE; EARLY-CHILDHOOD; SENSITIZATION; ENDOTOXIN; ATOPY; ENVIRONMENT; COMMUNITY; URBAN; SIZE	Background: Studies in Europe have reported a reduced prevalence of allergy in farmers children. We aimed to determine if there is a similar reduction in allergy among New Zealand farm children. Methods: Two hundred and ninety-three children participated (60%) aged 7-10 years, from selected schools in small towns and the surrounding rural area. Skin prick tests (SPT) to eight common allergens were performed. Parents completed questionnaires about allergic and infectious diseases, place of residence, exposure to animals, and diet, and they provided dust from the livingroom floor. Endotoxin was measured using an Limulus amoebocyte lysate (LAL) assay and Der p 1 using enzyme-linked immunoassay ( ELISA). Results: Current farm abode was found to increase the risk of having symptoms associated with allergy, but not SPT positivity. Independent inverse associations were found for early-life exposures: at least weekly consumption of yoghurt with hayfever (odds ratio (OR) = 0.3, 95% confidence intervals (CI) 0.1-0.7) and allergic rhinitis (OR = 0.3, 95% CI 0.2-0.7); any unpasteurized milk consumption with atopic eczema/dermatitis syndrome (AEDS) (OR = 0.2, 95% CI 0.1-0.8); cats inside or outside with hayfever (OR = 0.4, 95% CI 0.1-1. 0) and AEDS (OR = 0.4, 95% CI 0.2-0.8); dogs inside or outside with asthma (OR = 0.4, 95% CI 0.2-0.8); and pigs with SPT positivity (OR = 0.2, 95% CI 0.1-0.9). Conclusions: Despite finding a protective effect of early-life animal exposures, we found a greater prevalence of allergic disease on farms.	44	99	2002	9	10.1034/j.1398-9995.2002.t01-1-23644.x	Allergy; Immunology
The challenge of preventing environmentally related disease in young children: Community-based research in New York City. Rates of developmental and respiratory diseases are disproportionately high in underserved, minority populations such as those in New York City's Washington Heights, Harlem, and the South Bronx. Blacks and Latinos in these neighborhoods represent high risk groups for asthma, adverse birth outcomes, impaired development, and some types of cancer. The Columbia Center for Children's Environmental Health in Washington Heights uses molecular epidermiologic methods to study the health effects of urban indoor and outdoor air pollutants on children, prenatally and postnatally, in a cohort of over 500 African-American and Dominican (originally from the Dominican Republic) mothers and newborns. Extensive data are collected to determine exposures to particulate matter < 2.5 &mu;m in aerodynamic diameter (PM2.5), polycyclic aromatic hydrocarbons (PAHs), diesel exhaust particulate (DEP), nitrogen oxide, nonpersistent pesticides, home allergens (dust mite, mouse, cockroach), environmental tobacco smoke (ETS), and lead and other metals. Biomarkers, air sampling, and clinical assessments are used to study the effects of these exposures on children's increased risk for allergic sensitization, asthma and other respiratory disorders, impairment of neurocognitive and behavioral development, and potential cancer risk. The center conducts its research and community education in collaboration with 10 community-based health and environmental advocacy organizations. This unique academic-community partnership helps to guide the center's research so that it is most relevant to the context of the low-income, minority neighborhoods in which the cohort resides, and information is delivered back to these communities in meaningful ways. In turn, communities become better equipped to relay environmental health concerns to policy makers. In this paper we describe the center's research and its academic-community partnership and present some preliminary findings.. asthma| cancer| children| development| environmental health| prenatal| prevention| susceptibility|polycyclic aromatic-hydrocarbons| diesel exhaust particles| serum cotinine levels| molecular epidemiology| birth-weight| cancer prevention| indoor allergens| passive smoking| tobacco-smoke| risk-factors.	FEB-2002	asthma| cancer| children| development| environmental health| prenatal| prevention| susceptibility|polycyclic aromatic-hydrocarbons| diesel exhaust particles| serum cotinine levels| molecular epidemiology| birth-weight| cancer prevention| indoor allergens| passive smoking| tobacco-smoke| risk-factors	Perera, FP; Illman, SM; Kinney, PL; Whyatt, RM; Kelvin, EA; Shepard, P; Evans, D; Fullilove, M; Ford, J; Miller, RL; Mayer, IH; Rauh, VA	The challenge of preventing environmentally related disease in young children: Community-based research in New York City		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; cancer; children; development; environmental health; prenatal; prevention; susceptibility	POLYCYCLIC AROMATIC-HYDROCARBONS; DIESEL EXHAUST PARTICLES; SERUM COTININE LEVELS; MOLECULAR EPIDEMIOLOGY; BIRTH-WEIGHT; CANCER PREVENTION; INDOOR ALLERGENS; PASSIVE SMOKING; TOBACCO-SMOKE; RISK-FACTORS	Rates of developmental and respiratory diseases are disproportionately high in underserved, minority populations such as those in New York City's Washington Heights, Harlem, and the South Bronx. Blacks and Latinos in these neighborhoods represent high risk groups for asthma, adverse birth outcomes, impaired development, and some types of cancer. The Columbia Center for Children's Environmental Health in Washington Heights uses molecular epidermiologic methods to study the health effects of urban indoor and outdoor air pollutants on children, prenatally and postnatally, in a cohort of over 500 African-American and Dominican (originally from the Dominican Republic) mothers and newborns. Extensive data are collected to determine exposures to particulate matter < 2.5 &mu;m in aerodynamic diameter (PM2.5), polycyclic aromatic hydrocarbons (PAHs), diesel exhaust particulate (DEP), nitrogen oxide, nonpersistent pesticides, home allergens (dust mite, mouse, cockroach), environmental tobacco smoke (ETS), and lead and other metals. Biomarkers, air sampling, and clinical assessments are used to study the effects of these exposures on children's increased risk for allergic sensitization, asthma and other respiratory disorders, impairment of neurocognitive and behavioral development, and potential cancer risk. The center conducts its research and community education in collaboration with 10 community-based health and environmental advocacy organizations. This unique academic-community partnership helps to guide the center's research so that it is most relevant to the context of the low-income, minority neighborhoods in which the cohort resides, and information is delivered back to these communities in meaningful ways. In turn, communities become better equipped to relay environmental health concerns to policy makers. In this paper we describe the center's research and its academic-community partnership and present some preliminary findings.	91	99	2002	8		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Identification of continuous, allergenic regions of the major shrimp allergen Pen a 1 (tropomyosin). Background: Crustaceans and mollusks are a frequent cause of allergic reactions. The only major allergen identified in shrimp is the muscle protein tropomyosin; at least 80% of shrimp-allergic subjects react to tropomyosin. Furthermore, tropomyosin is an important allergen in other crustaceans such as lobsters, crabs and mollusks, as well as other arthropods such as house dust mites and cockroaches, and has been implied as the cause of clinical cross-sensitivity among invertebrates. In contrast, vertebrate tropomyosins are considered nonallergenic. Objective: The basis of the allergenicity of proteins has not yet been resolved. Thus, tropomyosin molecules provide an excellent opportunity to study the relationship between protein structure and allergenicity. The aim of the current study was to identify the IgE-binding regions of Pen a 1 and compare these regions with homologous sequences in other allergenic and nonallergenic tropomyosins. Methods: Forty-six overlapping peptides (length: 15 amino acids; offset: 6 amino acids) spanning the entire Pen a 1 molecule were synthesized and tested for IgE antibody reactivity with sera from 18 shrimp-allergic subjects to identify the IgE-binding regions of shrimp tropomyosin. Results: Based on the frequency and intensity of the IgE reactivities, five major IgE-binding regions were identified. All five major IgE-binding regions were 15-38 amino acids long. The major IgE-binding regions identified were: region 1: Pen a 1 (43-57); region 2: Pen a 1 (85-105); region 3: Pen a 1 (133148); region 4: Pen a 1 (187-202), and region 5: Pen a 1 (247-284). In addition, 22 peptides were categorized as minor IgE-binding regions, and 12 peptides did not bind any IgE antibodies. No substantial differences in amino acid group composition in the five IgE-binding regions compared to the whole molecule were detected. Sequence identities and similarities of the Pen a 1 IgE-binding regions with homologous regions of allergenic arthropod tropomyosins were as high as 100%, whereas identities and similarities with homologous vertebrate sequences ranged from 36 to 76% and 53 to 85%, respectively. Conclusion: Five major IgE-binding regions of the allergenic shrimp tropomyosin, Pen a 1, were identified which are positioned at regular intervals of approximately 42 amino acids (7 heptads), suggesting a relationship with the repetitive coiled-coil structure of the tropomyosin molecule. The high degree of similarity between Pen a 1 IgE-binding regions and homologous sequences in invertebrate tropomyosins and the lower percentage of similarity with homologous regions of vertebrate tropomyosins supports a structural basis for cross-reactivity of allergenic tropomyosins. Copyright (C) 2002 S. Karger AG, Basel.. tropomyosin| pen a 1| invertebrate allergens| ige-binding sequences|ige-binding epitopes| muscle protein tropomyosin| cross-reactive allergen| molecular characterization| mutational analysis| american cockroach| nitrocellulose| cloning| mite| immunotherapy.	JAN-2002	tropomyosin| pen a 1| invertebrate allergens| ige-binding sequences|ige-binding epitopes| muscle protein tropomyosin| cross-reactive allergen| molecular characterization| mutational analysis| american cockroach| nitrocellulose| cloning| mite| immunotherapy	Ayuso, R; Lehrer, SB; Reese, G	Identification of continuous, allergenic regions of the major shrimp allergen Pen a 1 (tropomyosin)		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	tropomyosin; Pen a 1; invertebrate allergens; IgE-binding sequences	IGE-BINDING EPITOPES; MUSCLE PROTEIN TROPOMYOSIN; CROSS-REACTIVE ALLERGEN; MOLECULAR CHARACTERIZATION; MUTATIONAL ANALYSIS; AMERICAN COCKROACH; NITROCELLULOSE; CLONING; MITE; IMMUNOTHERAPY	Background: Crustaceans and mollusks are a frequent cause of allergic reactions. The only major allergen identified in shrimp is the muscle protein tropomyosin; at least 80% of shrimp-allergic subjects react to tropomyosin. Furthermore, tropomyosin is an important allergen in other crustaceans such as lobsters, crabs and mollusks, as well as other arthropods such as house dust mites and cockroaches, and has been implied as the cause of clinical cross-sensitivity among invertebrates. In contrast, vertebrate tropomyosins are considered nonallergenic. Objective: The basis of the allergenicity of proteins has not yet been resolved. Thus, tropomyosin molecules provide an excellent opportunity to study the relationship between protein structure and allergenicity. The aim of the current study was to identify the IgE-binding regions of Pen a 1 and compare these regions with homologous sequences in other allergenic and nonallergenic tropomyosins. Methods: Forty-six overlapping peptides (length: 15 amino acids; offset: 6 amino acids) spanning the entire Pen a 1 molecule were synthesized and tested for IgE antibody reactivity with sera from 18 shrimp-allergic subjects to identify the IgE-binding regions of shrimp tropomyosin. Results: Based on the frequency and intensity of the IgE reactivities, five major IgE-binding regions were identified. All five major IgE-binding regions were 15-38 amino acids long. The major IgE-binding regions identified were: region 1: Pen a 1 (43-57); region 2: Pen a 1 (85-105); region 3: Pen a 1 (133148); region 4: Pen a 1 (187-202), and region 5: Pen a 1 (247-284). In addition, 22 peptides were categorized as minor IgE-binding regions, and 12 peptides did not bind any IgE antibodies. No substantial differences in amino acid group composition in the five IgE-binding regions compared to the whole molecule were detected. Sequence identities and similarities of the Pen a 1 IgE-binding regions with homologous regions of allergenic arthropod tropomyosins were as high as 100%, whereas identities and similarities with homologous vertebrate sequences ranged from 36 to 76% and 53 to 85%, respectively. Conclusion: Five major IgE-binding regions of the allergenic shrimp tropomyosin, Pen a 1, were identified which are positioned at regular intervals of approximately 42 amino acids (7 heptads), suggesting a relationship with the repetitive coiled-coil structure of the tropomyosin molecule. The high degree of similarity between Pen a 1 IgE-binding regions and homologous sequences in invertebrate tropomyosins and the lower percentage of similarity with homologous regions of vertebrate tropomyosins supports a structural basis for cross-reactivity of allergenic tropomyosins. Copyright (C) 2002 S. Karger AG, Basel.	38	99	2002	11	10.1159/000048166	Allergy; Immunology
A tale of two cities: Effects of air pollution on hospital admissions in Hong Kong and London compared. The causal interpretation of reported associations between daily air pollution and daily admissions requires consideration of residual confounding, correlation between pollutants, and effect modification. If results obtained in Hong Kong and London-which differ in climate, lifestyle, and many other respects-were similar, a causal association would be supported. We used identical statistical methods for the analysis in each city. Associations between daily admissions and pollutant levels were estimated using Poisson regression. Nonparametric smoothing methods were used to model seasonality and the nonlinear dependence of admissions on temperature, humidity, and influenza admissions. For respiratory, admissions (greater than or equal to 65 years of age), significant positive associations were observed with particulate matter < 10 mum in aerodynamic diameter (PM10), nitrogen dioxide, sulfur dioxide, and ozone in both cities. These associations tended to be stronger at shorter lags in Hong Kong and at longer lap in London. Associations were stronger in the cool season in Hong Kong and in the warm season in London, periods during which levels of humidity are at their lowest in each city. For cardiac admissions (all ages) in both cities, significant positive associations were observed for PM10, NO2, and SO2 with similar lag patterns. Associations tended to be stronger in the cool season. The associations with NO2 and SO2 were the most robust in two-pollutant models. Patterns of association for pollutants with ischemic heart disease were similar in the two cities. The associations between O-3 and cardiac admissions were negative in London but positive in Hong Kong. We conclude that air pollution has remarkably similar associations with daily cardiorespiratory admissions in both cities, in spite of considerable differences between cities in social, lifestyle, and environmental factors. The results strengthen the argument that air pollution causes detrimental short-term health effects.. air pollution| cardiac and respiratory hospital admissions| daily time-series| hong kong| london|short-term associations| mortality| diseases| philadelphia| asthma.	JAN-2002	air pollution| cardiac and respiratory hospital admissions| daily time-series| hong kong| london|short-term associations| mortality| diseases| philadelphia| asthma	Wong, CM; Atkinson, RW; Anderson, HR; Hedley, AJ; Ma, S; Chau, PYK; Lam, TH	A tale of two cities: Effects of air pollution on hospital admissions in Hong Kong and London compared		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; cardiac and respiratory hospital admissions; daily time-series; Hong Kong; London	SHORT-TERM ASSOCIATIONS; MORTALITY; DISEASES; PHILADELPHIA; ASTHMA	The causal interpretation of reported associations between daily air pollution and daily admissions requires consideration of residual confounding, correlation between pollutants, and effect modification. If results obtained in Hong Kong and London-which differ in climate, lifestyle, and many other respects-were similar, a causal association would be supported. We used identical statistical methods for the analysis in each city. Associations between daily admissions and pollutant levels were estimated using Poisson regression. Nonparametric smoothing methods were used to model seasonality and the nonlinear dependence of admissions on temperature, humidity, and influenza admissions. For respiratory, admissions (greater than or equal to 65 years of age), significant positive associations were observed with particulate matter < 10 mum in aerodynamic diameter (PM10), nitrogen dioxide, sulfur dioxide, and ozone in both cities. These associations tended to be stronger at shorter lags in Hong Kong and at longer lap in London. Associations were stronger in the cool season in Hong Kong and in the warm season in London, periods during which levels of humidity are at their lowest in each city. For cardiac admissions (all ages) in both cities, significant positive associations were observed for PM10, NO2, and SO2 with similar lag patterns. Associations tended to be stronger in the cool season. The associations with NO2 and SO2 were the most robust in two-pollutant models. Patterns of association for pollutants with ischemic heart disease were similar in the two cities. The associations between O-3 and cardiac admissions were negative in London but positive in Hong Kong. We conclude that air pollution has remarkably similar associations with daily cardiorespiratory admissions in both cities, in spite of considerable differences between cities in social, lifestyle, and environmental factors. The results strengthen the argument that air pollution causes detrimental short-term health effects.	40	99	2002	11		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Remodeling in response to infection and injury - Airway inflammation and hypersecretion of mucus in smoking subjects with chronic obstructive pulmonary disease. Airway epithelium represents the first line of defense against toxic inhalants. In some subjects, cigarette smoking causes airway inflammation, hypersecretion of mucus, and poorly reversible airflow limitation through mechanisms that are still largely unknown. Likewise, it is unclear why only some smokers develop chronic obstructive pulmonary disease (COPD). Two cell types consistently result in relation to chronic airflow limitation in COPD: neutrophils and CD8(+) cells. Neutrophils are compartmentalized in the mucosal surface of the airways and air spaces, that is, the epithelium and lumen, whereas CD8(+) cells exhibit a more extensive distribution along the subepithelial zone of the airways and lung parenchyma, including alveolar walls and arteries. This pattern of inflammatory cell distribution is observed in mild or moderate COPD, and in patients who have developed COPD, it is not modified by smoking cessation. The number of neutrophils further increases in the submucosa of patients with severe COPD, suggesting a role for these cells in the progression of the disease. Hypersecretion of mucus is a major manifestation in COPD. Mucus is produced by bronchial glands and goblet cells lining the airway epithelium. Unlike mucous gland enlargement, greater mucosal inflammation is associated with sputum production. Whereas neutrophil infiltration of submucosal glands occurs only in smokers with COPD, goblet cell hyperplasia in peripheral airways occurs both in smokers with or without COPD, suggesting that the major determinant of goblet cell hyperplasia is cigarette smoke itself.. histology| sputum cytology| glands| goblet cells| biopsies|neutrophil chemotactic factor| t-cell clones| chronic-bronchitis| peripheral airways| flow limitation| induced sputum| lymphocytes-t| up-regulation| smokers| asthma.	NOV 15-2001	histology| sputum cytology| glands| goblet cells| biopsies|neutrophil chemotactic factor| t-cell clones| chronic-bronchitis| peripheral airways| flow limitation| induced sputum| lymphocytes-t| up-regulation| smokers| asthma	Maestrelli, P; Saetta, M; Mapp, CE; Fabbri, LM	Remodeling in response to infection and injury - Airway inflammation and hypersecretion of mucus in smoking subjects with chronic obstructive pulmonary disease		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	histology; sputum cytology; glands; goblet cells; biopsies	NEUTROPHIL CHEMOTACTIC FACTOR; T-CELL CLONES; CHRONIC-BRONCHITIS; PERIPHERAL AIRWAYS; FLOW LIMITATION; INDUCED SPUTUM; LYMPHOCYTES-T; UP-REGULATION; SMOKERS; ASTHMA	Airway epithelium represents the first line of defense against toxic inhalants. In some subjects, cigarette smoking causes airway inflammation, hypersecretion of mucus, and poorly reversible airflow limitation through mechanisms that are still largely unknown. Likewise, it is unclear why only some smokers develop chronic obstructive pulmonary disease (COPD). Two cell types consistently result in relation to chronic airflow limitation in COPD: neutrophils and CD8(+) cells. Neutrophils are compartmentalized in the mucosal surface of the airways and air spaces, that is, the epithelium and lumen, whereas CD8(+) cells exhibit a more extensive distribution along the subepithelial zone of the airways and lung parenchyma, including alveolar walls and arteries. This pattern of inflammatory cell distribution is observed in mild or moderate COPD, and in patients who have developed COPD, it is not modified by smoking cessation. The number of neutrophils further increases in the submucosa of patients with severe COPD, suggesting a role for these cells in the progression of the disease. Hypersecretion of mucus is a major manifestation in COPD. Mucus is produced by bronchial glands and goblet cells lining the airway epithelium. Unlike mucous gland enlargement, greater mucosal inflammation is associated with sputum production. Whereas neutrophil infiltration of submucosal glands occurs only in smokers with COPD, goblet cell hyperplasia in peripheral airways occurs both in smokers with or without COPD, suggesting that the major determinant of goblet cell hyperplasia is cigarette smoke itself.	50	99	2001	5		General & Internal Medicine; Respiratory System
Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment. Background-Nitric oxide (NO) and prostanoids are mediators of vascular and bronchial tone that are postulated to be involved in asthma. increased levels of both are found in asthmatic subjects and are synthesised by enzymes that have cytokine inducible forms: inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), respectively. We hypothesised that the in vivo expression of iNOS and COX-2 in the airways would be increased in asthma, and that these cytokine inducible enzymes may represent targets for regulation by corticosteroid treatment. Methods-Bronchial biopsy specimens were obtained from three groups of subjects: atopic asthmatics treated with p, agonists alone (n=7), atopic asthmatics additionally receiving regular treatment with corticosteroids (n=8), and nonasthmatic control subjects (n=10). Expression of iNOS and COX-2 mRNA and immunoreactive protein was studied using in situ hybridisation and quantitative immunohistochemistry. Results-Immunoreactivity and the hybridisation signal for iNOS and COX-2 were mainly localised in the airway epithelium. The proportion of epithelium immunostained was significantly greater in the non-steroid treated asthmatic subjects (iNOS 8.6 (1.8)%; COX-2 26.3 (4.6)%) than either the steroid treated asthmatics (iNOS 3.4 (1.0)%, p=0.009; COX-2 13.0 (0.6)%, p=0.0015) or the non-asthmatic controls (iNOS 4.2 (0.9)%, p=0.018; COX-2 11.6 (0.6)%, p=0.0003). Similarly, the hybridisation signal was stronger in the non-steroid treated group of asthmatic subjects than in the other two groups. Conclusions-These findings highlight the potential role of the airway epithelium both as a contributor to the inflammatory process in asthma and as a target for inhaled corticosteroid treatment in this disease.. asthma| corticosteroids| immunohistochemistry| in situ hybridisation| nitric oxide synthase| cyclo-oxygenase (cox)|human endothelial-cells| exhaled air| human tissues| cyclooxygenase| cdna| prostaglandin-d2| localization| inhalation| induction| cloning.	MAY-2001	asthma| corticosteroids| immunohistochemistry| in situ hybridisation| nitric oxide synthase| cyclo-oxygenase (cox)|human endothelial-cells| exhaled air| human tissues| cyclooxygenase| cdna| prostaglandin-d2| localization| inhalation| induction| cloning	Redington, AE; Meng, QH; Springall, DR; Evans, TJ; Creminon, C; Maclouf, J; Holgate, ST; Howarth, PH; Polak, JM	Increased expression of inducible nitric oxide synthase and cyclo-oxygenase-2 in the airway epithelium of asthmatic subjects and regulation by corticosteroid treatment		THORAX	asthma; corticosteroids; immunohistochemistry; in situ hybridisation; nitric oxide synthase; cyclo-oxygenase (COX)	HUMAN ENDOTHELIAL-CELLS; EXHALED AIR; HUMAN TISSUES; CYCLOOXYGENASE; CDNA; PROSTAGLANDIN-D2; LOCALIZATION; INHALATION; INDUCTION; CLONING	Background-Nitric oxide (NO) and prostanoids are mediators of vascular and bronchial tone that are postulated to be involved in asthma. increased levels of both are found in asthmatic subjects and are synthesised by enzymes that have cytokine inducible forms: inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), respectively. We hypothesised that the in vivo expression of iNOS and COX-2 in the airways would be increased in asthma, and that these cytokine inducible enzymes may represent targets for regulation by corticosteroid treatment. Methods-Bronchial biopsy specimens were obtained from three groups of subjects: atopic asthmatics treated with p, agonists alone (n=7), atopic asthmatics additionally receiving regular treatment with corticosteroids (n=8), and nonasthmatic control subjects (n=10). Expression of iNOS and COX-2 mRNA and immunoreactive protein was studied using in situ hybridisation and quantitative immunohistochemistry. Results-Immunoreactivity and the hybridisation signal for iNOS and COX-2 were mainly localised in the airway epithelium. The proportion of epithelium immunostained was significantly greater in the non-steroid treated asthmatic subjects (iNOS 8.6 (1.8)%; COX-2 26.3 (4.6)%) than either the steroid treated asthmatics (iNOS 3.4 (1.0)%, p=0.009; COX-2 13.0 (0.6)%, p=0.0015) or the non-asthmatic controls (iNOS 4.2 (0.9)%, p=0.018; COX-2 11.6 (0.6)%, p=0.0003). Similarly, the hybridisation signal was stronger in the non-steroid treated group of asthmatic subjects than in the other two groups. Conclusions-These findings highlight the potential role of the airway epithelium both as a contributor to the inflammatory process in asthma and as a target for inhaled corticosteroid treatment in this disease.	43	99	2001	7	10.1136/thorax.56.5.351	Respiratory System
Tobacco's toll: Implications for the pediatrician. The disease of tobacco addiction, which is pervasive in the United States, begins in childhood and adolescence. Twenty-five percent of the population regularly uses tobacco, despite evidence that such use is the leading preventable cause of death in the United States. Tobacco use reportedly kills 2.5 times as many people each year as alcohol and drug abuse combined. According to 1998 data from the World Health Organization, there were 1.1 billion smokers worldwide and 10 000 tobacco-related deaths per day. Furthermore, in the United States, 43% of children aged 2 to 11 years are exposed to environmental tobacco smoke, which has been implicated in sudden infant death syndrome, low birth weight, asthma, middle ear disease, pneumonia, cough, and upper respiratory infection. Pediatricians play a crucial role in reducing both tobacco use (by children, adolescents, and their parents) and exposure to tobacco smoke and should rank this among their highest health prevention priorities.. cigarette-smoking| adolescents| prevention| depression| alcohol| youth| risk.	APR-2001	cigarette-smoking| adolescents| prevention| depression| alcohol| youth| risk	Jacobs, EA; Joffe, A; Knight, JR; Kulig, J; Rogers, PD	Tobacco's toll: Implications for the pediatrician		PEDIATRICS		CIGARETTE-SMOKING; ADOLESCENTS; PREVENTION; DEPRESSION; ALCOHOL; YOUTH; RISK	The disease of tobacco addiction, which is pervasive in the United States, begins in childhood and adolescence. Twenty-five percent of the population regularly uses tobacco, despite evidence that such use is the leading preventable cause of death in the United States. Tobacco use reportedly kills 2.5 times as many people each year as alcohol and drug abuse combined. According to 1998 data from the World Health Organization, there were 1.1 billion smokers worldwide and 10 000 tobacco-related deaths per day. Furthermore, in the United States, 43% of children aged 2 to 11 years are exposed to environmental tobacco smoke, which has been implicated in sudden infant death syndrome, low birth weight, asthma, middle ear disease, pneumonia, cough, and upper respiratory infection. Pediatricians play a crucial role in reducing both tobacco use (by children, adolescents, and their parents) and exposure to tobacco smoke and should rank this among their highest health prevention priorities.	38	99	2001	5		Pediatrics
Influence of ambient fungal spores on emergency visits for asthma to a regional children's hospital. The impact of ambient aeroallergens on morbidity from childhood asthma is largely unknown. To address this issue, we studied the association between daily emergency department visits for asthma to a childrens' hospital, and daily concentrations of both pollen grains and fungal spores during a 5-yr period between 1993 and 1997. Air pollution and meteorological data accounted for in the analyses included ozone, nitrogen dioxide, sulfur dioxide, sulfates, temperature, barometric pressure, and relative humidity. The daily number of asthma visits ranged from 0 to 36 per day with an average of 7.5. Fungal spores, but not pollen grains, were associated with visits (p < 0.05). The percentage increase associated with each group, independent of the others, was 1.9% (SE 0.9) for deuteromycetes, 4.1% (1.6) for basidiomycetes, 2.8% (1.0) for ascomycetes, and 8.8% for these spores combined. In summary, fungal spores account for a significant proportion of the asthma exacerbations in children that prompt an emergency department visit.. air-pollution| respiratory-diseases| canadian cities| room visits| particulate| association| alternaria| pollen| ozone.	DEC-2000	air-pollution| respiratory-diseases| canadian cities| room visits| particulate| association| alternaria| pollen| ozone	Dales, RE; Cakmak, S; Burnett, RT; Judek, S; Coates, F; Brook, JR	Influence of ambient fungal spores on emergency visits for asthma to a regional children's hospital		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		AIR-POLLUTION; RESPIRATORY-DISEASES; CANADIAN CITIES; ROOM VISITS; PARTICULATE; ASSOCIATION; ALTERNARIA; POLLEN; OZONE	The impact of ambient aeroallergens on morbidity from childhood asthma is largely unknown. To address this issue, we studied the association between daily emergency department visits for asthma to a childrens' hospital, and daily concentrations of both pollen grains and fungal spores during a 5-yr period between 1993 and 1997. Air pollution and meteorological data accounted for in the analyses included ozone, nitrogen dioxide, sulfur dioxide, sulfates, temperature, barometric pressure, and relative humidity. The daily number of asthma visits ranged from 0 to 36 per day with an average of 7.5. Fungal spores, but not pollen grains, were associated with visits (p < 0.05). The percentage increase associated with each group, independent of the others, was 1.9% (SE 0.9) for deuteromycetes, 4.1% (1.6) for basidiomycetes, 2.8% (1.0) for ascomycetes, and 8.8% for these spores combined. In summary, fungal spores account for a significant proportion of the asthma exacerbations in children that prompt an emergency department visit.	25	99	2000	4		General & Internal Medicine; Respiratory System
Airway hyperresponsiveness in elite athletes. It has been suggested that high-level training could contribute to the development of airway hyperresponsiveness (AHR), but the comparative effects of different sports on airway function remains to be determined. We evaluated 150 nonsmoking volunteers 18 to 55 yr of age; 100 athletes divided into four subgroups of 25 subjects each according to the predominant estimated hydrocaloric characteristic of ambient air inhaled during training: dry air (DA), cold air (CA), humid air (HA) and a mixture of dry and humid air (MA), and 50 sedentary subjects. Each subject had a respiratory questionnaire, a methacholine challenge, allergy skin-prick tests, and heart rate variability recording for evaluation of parasympathetic tone. The athletes had a 49% prevalence of AHR (PC20 < 16 mg/ml), with a mean PC20 of 16.9 mg/ml, compared with 28% (PC20: 35.4) in sedentary subjects (p = 0.009). The prevalence (%) of AHR and mean PC,, (mg/ml) varied as followed in the four subgroups of athletes: DA: 32% and 30.9; CA: 52% and 15.8; HA: 76% and 7.3; and MA: 32% and 21.5 (p = 0.002). The estimated parasympathetic tone was higher in athletes (p < 0.001), but this parameter showed only a weak correlation with PC20 (r = -0.17, p = 0.04). This study has shown a significantly higher prevalence of AHR in athletes than in the control group because of the higher prevalence in the CA and HA groups. Parasympathetic activity may act as modulator of airway responsiveness, but the increased prevalence of AHR in our athlete population may be related to the type and possibly the content of inhaled air during training.. indoor swimming pools| exercise-induced bronchospasm| cross-country skiers| ice hockey players| bronchial responsiveness| high prevalence| figure skaters| induced asthma| exposure| risk.	MAY-2000	indoor swimming pools| exercise-induced bronchospasm| cross-country skiers| ice hockey players| bronchial responsiveness| high prevalence| figure skaters| induced asthma| exposure| risk	Langdeau, JB; Turcotte, H; Bowie, DM; Jobin, J; Desgagne, P; Boulet, LP	Airway hyperresponsiveness in elite athletes		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		INDOOR SWIMMING POOLS; EXERCISE-INDUCED BRONCHOSPASM; CROSS-COUNTRY SKIERS; ICE HOCKEY PLAYERS; BRONCHIAL RESPONSIVENESS; HIGH PREVALENCE; FIGURE SKATERS; INDUCED ASTHMA; EXPOSURE; RISK	It has been suggested that high-level training could contribute to the development of airway hyperresponsiveness (AHR), but the comparative effects of different sports on airway function remains to be determined. We evaluated 150 nonsmoking volunteers 18 to 55 yr of age; 100 athletes divided into four subgroups of 25 subjects each according to the predominant estimated hydrocaloric characteristic of ambient air inhaled during training: dry air (DA), cold air (CA), humid air (HA) and a mixture of dry and humid air (MA), and 50 sedentary subjects. Each subject had a respiratory questionnaire, a methacholine challenge, allergy skin-prick tests, and heart rate variability recording for evaluation of parasympathetic tone. The athletes had a 49% prevalence of AHR (PC20 < 16 mg/ml), with a mean PC20 of 16.9 mg/ml, compared with 28% (PC20: 35.4) in sedentary subjects (p = 0.009). The prevalence (%) of AHR and mean PC,, (mg/ml) varied as followed in the four subgroups of athletes: DA: 32% and 30.9; CA: 52% and 15.8; HA: 76% and 7.3; and MA: 32% and 21.5 (p = 0.002). The estimated parasympathetic tone was higher in athletes (p < 0.001), but this parameter showed only a weak correlation with PC20 (r = -0.17, p = 0.04). This study has shown a significantly higher prevalence of AHR in athletes than in the control group because of the higher prevalence in the CA and HA groups. Parasympathetic activity may act as modulator of airway responsiveness, but the increased prevalence of AHR in our athlete population may be related to the type and possibly the content of inhaled air during training.	35	99	2000	6		General & Internal Medicine; Respiratory System
Molecular pathology of allergic disease - II: Upper airway disease. Allergic upper airway diseases such as allergic rhinitis and chronic sinusitis are an increasing problem. Although the pathogenesis remains elusive, an individual's genetic predisposition as well as exposure to the allergen are currently considered factors in their development. Clinical symptoms of sneezing, rhinorrhea, and congestion are primarily a consequence of granulocyte release of chemical mediators such as histamine, prostanoids, and leukotrienes as well as the infiltration of inflammatory cells, Observations subsequent to allergen provocation are comparable to natural exposure and as such much of our understanding of allergic responses is derived from this model, A prominence of CD4(+) T cells and eosinophils, synthesis and release of T(H)2 cytokines, and the coordinate expression of chemokines and adhesion molecules are all characteristic of the allergic response observed in rhinitis and sinusitis. Corticosteroids and immunotherapy target these inflammatory processes and have been observed to successfully reduce and shift the predominantly T(H)2 environment toward T(H)1 cytokine expression. As our understanding of the pathophysiologic features of allergic upper airway disease improves, as well as the relationship between their development and that of lower airway disease, new strategies of diagnosis and treatment will allow for more effective modulation of the allergic process and associated morbidity.. allergic rhinitis| chronic sinusitis| inflammation| cytokines| chemokines|colony-stimulating factor| messenger-rna expression| major basic-protein| endothelial adhesion molecules| chronic hyperplastic sinusitis| grass-pollen immunotherapy| nitric-oxide synthase| phase nasal responses| necrosis-factor-alpha| fc-epsilon-ri.	FEB-2000	allergic rhinitis| chronic sinusitis| inflammation| cytokines| chemokines|colony-stimulating factor| messenger-rna expression| major basic-protein| endothelial adhesion molecules| chronic hyperplastic sinusitis| grass-pollen immunotherapy| nitric-oxide synthase| phase nasal responses| necrosis-factor-alpha| fc-epsilon-ri	Christodoulopoulos, P; Cameron, L; Durham, S; Hamid, Q	Molecular pathology of allergic disease - II: Upper airway disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergic rhinitis; chronic sinusitis; inflammation; cytokines; chemokines	COLONY-STIMULATING FACTOR; MESSENGER-RNA EXPRESSION; MAJOR BASIC-PROTEIN; ENDOTHELIAL ADHESION MOLECULES; CHRONIC HYPERPLASTIC SINUSITIS; GRASS-POLLEN IMMUNOTHERAPY; NITRIC-OXIDE SYNTHASE; PHASE NASAL RESPONSES; NECROSIS-FACTOR-ALPHA; FC-EPSILON-RI	Allergic upper airway diseases such as allergic rhinitis and chronic sinusitis are an increasing problem. Although the pathogenesis remains elusive, an individual's genetic predisposition as well as exposure to the allergen are currently considered factors in their development. Clinical symptoms of sneezing, rhinorrhea, and congestion are primarily a consequence of granulocyte release of chemical mediators such as histamine, prostanoids, and leukotrienes as well as the infiltration of inflammatory cells, Observations subsequent to allergen provocation are comparable to natural exposure and as such much of our understanding of allergic responses is derived from this model, A prominence of CD4(+) T cells and eosinophils, synthesis and release of T(H)2 cytokines, and the coordinate expression of chemokines and adhesion molecules are all characteristic of the allergic response observed in rhinitis and sinusitis. Corticosteroids and immunotherapy target these inflammatory processes and have been observed to successfully reduce and shift the predominantly T(H)2 environment toward T(H)1 cytokine expression. As our understanding of the pathophysiologic features of allergic upper airway disease improves, as well as the relationship between their development and that of lower airway disease, new strategies of diagnosis and treatment will allow for more effective modulation of the allergic process and associated morbidity.	164	99	2000	13	10.1016/S0091-6749(00)90068-X	Allergy; Immunology
Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Changes in epigenetic marks such as DNA methylation and histone acetylation are associated with a broad range of disease traits, including cancer, asthma, metabolic disorders, and various reproductive conditions. It seems plausible that changes in epigenetic state may be induced by environmental exposures such as malnutrition, tobacco smoke, air pollutants, metals, organic chemicals, other sources of oxidative stress, and the microbiome, particularly if the exposure occurs during key periods of development. Thus, epigenetic changes could represent an important pathway by which environmental factors influence disease risks, both within individuals and across generations. We discuss some of the challenges in studying epigenetic mediation of pathogenesis and describe some unique opportunities for exploring these phenomena.. monozygotic twins discordant| dna methylation patterns| diethylstilbestrol in-utero| dietary-protein restriction| epigenome-wide association| gene-expression profiles| squamous-cell carcinoma| colorectal-cancer risk| cpg island methylation| ifn-gamma promoter.	OCT-2012	monozygotic twins discordant| dna methylation patterns| diethylstilbestrol in-utero| dietary-protein restriction| epigenome-wide association| gene-expression profiles| squamous-cell carcinoma| colorectal-cancer risk| cpg island methylation| ifn-gamma promoter	Cortessis, VK; Thomas, DC; Levine, AJ; Breton, CV; Mack, TM; Siegmund, KD; Haile, RW; Laird, PW	Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships		HUMAN GENETICS		MONOZYGOTIC TWINS DISCORDANT; DNA METHYLATION PATTERNS; DIETHYLSTILBESTROL IN-UTERO; DIETARY-PROTEIN RESTRICTION; EPIGENOME-WIDE ASSOCIATION; GENE-EXPRESSION PROFILES; SQUAMOUS-CELL CARCINOMA; COLORECTAL-CANCER RISK; CPG ISLAND METHYLATION; IFN-GAMMA PROMOTER	Changes in epigenetic marks such as DNA methylation and histone acetylation are associated with a broad range of disease traits, including cancer, asthma, metabolic disorders, and various reproductive conditions. It seems plausible that changes in epigenetic state may be induced by environmental exposures such as malnutrition, tobacco smoke, air pollutants, metals, organic chemicals, other sources of oxidative stress, and the microbiome, particularly if the exposure occurs during key periods of development. Thus, epigenetic changes could represent an important pathway by which environmental factors influence disease risks, both within individuals and across generations. We discuss some of the challenges in studying epigenetic mediation of pathogenesis and describe some unique opportunities for exploring these phenomena.	256	98	2012	25	10.1007/s00439-012-1189-8	Genetics & Heredity
A systematic quantitative review of urban tree benefits, costs, and assessment methods across cities in different climatic zones. Urban trees can potentially mitigate environmental degradation accompanying rapid urbanisation via a range of tree benefits and services. But uncertainty exists about the extent of tree benefits and services because urban trees also impose costs (e.g. asthma) and may create hazards (e.g. windthrow). Few researchers have systematically assessed how urban tree benefits and costs vary across different cities, geographic scales and climates. This paper provides a quantitative review of 115 original urban tree studies, examining: (i) research locations, (ii) research methods, and (iii) assessment techniques for tree services and disservices. Researchers published findings in 33 journals from diverse disciplines including: forestry, land use planning, ecology, and economics. Research has been geographically concentrated (64% of studies were conducted in North America). Nearly all studies (91.3%) used quantitative research, and most studies (60%) employed natural science methods. Demonstrated tree benefits include: economic, social, health, visual and aesthetic benefits; identified ecosystem services include: carbon sequestration, air quality improvement, storm water attenuation, and energy conservation. Disservices include: maintenance costs, light attenuation, infrastructure damage and health problems, among others. Additional research is required to better inform public policy, including comparative assessment of tree services and disservices, and assessment of urban residents and land managers' understanding of tree benefits and costs. (c) 2012 Elsevier GmbH. All rights reserved.. cities| ecosystem services| ecosystem disservices| land use policy| trees|valuing ecosystem services| street tree| carbon storage| forest structure| shade trees| decision-making| green space| air-quality| pollution mitigation| united-states.	2012	cities| ecosystem services| ecosystem disservices| land use policy| trees|valuing ecosystem services| street tree| carbon storage| forest structure| shade trees| decision-making| green space| air-quality| pollution mitigation| united-states	Roy, S; Byrne, J; Pickering, C	A systematic quantitative review of urban tree benefits, costs, and assessment methods across cities in different climatic zones		URBAN FORESTRY & URBAN GREENING	Cities; Ecosystem services; Ecosystem disservices; Land use policy; Trees	VALUING ECOSYSTEM SERVICES; STREET TREE; CARBON STORAGE; FOREST STRUCTURE; SHADE TREES; DECISION-MAKING; GREEN SPACE; AIR-QUALITY; POLLUTION MITIGATION; UNITED-STATES	Urban trees can potentially mitigate environmental degradation accompanying rapid urbanisation via a range of tree benefits and services. But uncertainty exists about the extent of tree benefits and services because urban trees also impose costs (e.g. asthma) and may create hazards (e.g. windthrow). Few researchers have systematically assessed how urban tree benefits and costs vary across different cities, geographic scales and climates. This paper provides a quantitative review of 115 original urban tree studies, examining: (i) research locations, (ii) research methods, and (iii) assessment techniques for tree services and disservices. Researchers published findings in 33 journals from diverse disciplines including: forestry, land use planning, ecology, and economics. Research has been geographically concentrated (64% of studies were conducted in North America). Nearly all studies (91.3%) used quantitative research, and most studies (60%) employed natural science methods. Demonstrated tree benefits include: economic, social, health, visual and aesthetic benefits; identified ecosystem services include: carbon sequestration, air quality improvement, storm water attenuation, and energy conservation. Disservices include: maintenance costs, light attenuation, infrastructure damage and health problems, among others. Additional research is required to better inform public policy, including comparative assessment of tree services and disservices, and assessment of urban residents and land managers' understanding of tree benefits and costs. (c) 2012 Elsevier GmbH. All rights reserved.	176	98	2012	13	10.1016/j.ufug.2012.06.006	Plant Sciences; Environmental Sciences & Ecology; Forestry; Urban Studies
Investigation of relative risk estimates from studies of the same population with contrasting response rates and designs. Background: There is little empirical evidence regarding the generalisability of relative risk estimates from studies which have relatively low response rates or are of limited representativeness. The aim of this study was to investigate variation in exposure-outcome relationships in studies of the same population with different response rates and designs by comparing estimates from the 45 and Up Study, a population-based cohort study (self-administered postal questionnaire, response rate 18%), and the New South Wales Population Health Survey (PHS) (computer-assisted telephone interview, response rate similar to 60%). Methods: Logistic regression analysis of questionnaire data from 45 and Up Study participants (n = 101,812) and 2006/2007 PHS participants (n = 14,796) was used to calculate prevalence estimates and odds ratios (ORs) for comparable variables, adjusting for age, sex and remoteness. ORs were compared using Wald tests modelling each study separately, with and without sampling weights. Results: Prevalence of some outcomes (smoking, private health insurance, diabetes, hypertension, asthma) varied between the two studies. For highly comparable questionnaire items, exposure-outcome relationship patterns were almost identical between the studies and ORs for eight of the ten relationships examined did not differ significantly. For questionnaire items that were only moderately comparable, the nature of the observed relationships did not differ materially between the two studies, although many ORs differed significantly. Conclusions: These findings show that for a broad range of risk factors, two studies of the same population with varying response rate, sampling frame and mode of questionnaire administration yielded consistent estimates of exposure-outcome relationships. However, ORs varied between the studies where they did not use identical questionnaire items.. survey nonresponse| psychological distress| cohort profile| follow-up| bias| health| scores.	APR 1-2010	survey nonresponse| psychological distress| cohort profile| follow-up| bias| health| scores	Mealing, NM; Banks, E; Jorm, LR; Steel, DG; Clements, MS; Rogers, KD	Investigation of relative risk estimates from studies of the same population with contrasting response rates and designs		BMC MEDICAL RESEARCH METHODOLOGY		SURVEY NONRESPONSE; PSYCHOLOGICAL DISTRESS; COHORT PROFILE; FOLLOW-UP; BIAS; HEALTH; SCORES	Background: There is little empirical evidence regarding the generalisability of relative risk estimates from studies which have relatively low response rates or are of limited representativeness. The aim of this study was to investigate variation in exposure-outcome relationships in studies of the same population with different response rates and designs by comparing estimates from the 45 and Up Study, a population-based cohort study (self-administered postal questionnaire, response rate 18%), and the New South Wales Population Health Survey (PHS) (computer-assisted telephone interview, response rate similar to 60%). Methods: Logistic regression analysis of questionnaire data from 45 and Up Study participants (n = 101,812) and 2006/2007 PHS participants (n = 14,796) was used to calculate prevalence estimates and odds ratios (ORs) for comparable variables, adjusting for age, sex and remoteness. ORs were compared using Wald tests modelling each study separately, with and without sampling weights. Results: Prevalence of some outcomes (smoking, private health insurance, diabetes, hypertension, asthma) varied between the two studies. For highly comparable questionnaire items, exposure-outcome relationship patterns were almost identical between the studies and ORs for eight of the ten relationships examined did not differ significantly. For questionnaire items that were only moderately comparable, the nature of the observed relationships did not differ materially between the two studies, although many ORs differed significantly. Conclusions: These findings show that for a broad range of risk factors, two studies of the same population with varying response rate, sampling frame and mode of questionnaire administration yielded consistent estimates of exposure-outcome relationships. However, ORs varied between the studies where they did not use identical questionnaire items.	38	98	2010	12	10.1186/1471-2288-10-26	Health Care Sciences & Services
Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber. Background: The efficacy and safety of a 5-grass-pollen sublingual immunotherapy (SLIT) tablet (Stallergenes SA, Antony, France) have been evaluated in clinical studies during the pollen season. The allergen challenge chamber (ACC) has been developed as a pharmacodynamic assessment tool to control the environmental allergens and to avoid all problems associated with unpredictable pollen seasons. Objective: We sought to evaluate the onset of action and efficacy of 300-IR (index of reactivity) SLIT tablets by using an ACC. Methods: Patients with grass pollen-induced rhinoconjunctivitis were randomized into the active or placebo groups. A standardized allergen challenge with grass pollen and symptom evaluation every 15 minutes was performed at baseline, 1 week, and 1, 2, and 4 months of treatment. The primary end point was the average rhinoconjunctivitis total symptom score (ARTSS). Allergen-specific basophil activation, T-cell proliferation, and plasmatic IgE and IgG responses were assessed before and after treatment. Results: In the intention-to-treat population (n = 89) a significant treatment effect was achieved after the first month (P = .0042) and second month (P = .0203) and was maintained through to the fourth month (P = .0007). In the active group the ARTSS (means +/- SDs) decreased at each challenge: week 1, 7.40 +/- 2.682; month 1, 5.89 +/- 2.431; month 2, 5.09 +/- 2.088; and month 4, 4.85 +/- 1.999. An improvement (vs placebo) of 29.3% for the mean ARTSS ( median, 33.3%) was observed at end point. Furthermore, the induction of grass pollen allergen specific IgGs was associated with clinical response. The most frequent adverse reactions were local: oral pruritus, ear pruritus, and throat irritation. Conclusions: In this ACC study the 300-IR 5-grass-pollen SLIT tablets had a significant effect on rhinoconjunctivitis symptoms (vs placebo) from the first month of treatment onward. (J Allergy Clin Immunol 2009;124:471-7.). grass pollen| tablets| sublingual immunotherapy| allergen challenge chamber| vienna challenge chamber|grass-pollen| rhinitis| exposure| efficacy| placebo| symptoms| rhinoconjunctivitis| safety| flow.	SEP-2009	grass pollen| tablets| sublingual immunotherapy| allergen challenge chamber| vienna challenge chamber|grass-pollen| rhinitis| exposure| efficacy| placebo| symptoms| rhinoconjunctivitis| safety| flow	Horak, F; Zieglmayer, P; Zieglmayer, R; Lemell, P; Devillier, P; Montagut, A; Melac, M; Galvain, S; Jean-Alphonse, S; Van Overtvelt, L; Moingeon, P; Le Gall, M	Early onset of action of a 5-grass-pollen 300-IR sublingual immunotherapy tablet evaluated in an allergen challenge chamber		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Grass pollen; tablets; sublingual immunotherapy; allergen challenge chamber; Vienna Challenge Chamber	GRASS-POLLEN; RHINITIS; EXPOSURE; EFFICACY; PLACEBO; SYMPTOMS; RHINOCONJUNCTIVITIS; SAFETY; FLOW	Background: The efficacy and safety of a 5-grass-pollen sublingual immunotherapy (SLIT) tablet (Stallergenes SA, Antony, France) have been evaluated in clinical studies during the pollen season. The allergen challenge chamber (ACC) has been developed as a pharmacodynamic assessment tool to control the environmental allergens and to avoid all problems associated with unpredictable pollen seasons. Objective: We sought to evaluate the onset of action and efficacy of 300-IR (index of reactivity) SLIT tablets by using an ACC. Methods: Patients with grass pollen-induced rhinoconjunctivitis were randomized into the active or placebo groups. A standardized allergen challenge with grass pollen and symptom evaluation every 15 minutes was performed at baseline, 1 week, and 1, 2, and 4 months of treatment. The primary end point was the average rhinoconjunctivitis total symptom score (ARTSS). Allergen-specific basophil activation, T-cell proliferation, and plasmatic IgE and IgG responses were assessed before and after treatment. Results: In the intention-to-treat population (n = 89) a significant treatment effect was achieved after the first month (P = .0042) and second month (P = .0203) and was maintained through to the fourth month (P = .0007). In the active group the ARTSS (means +/- SDs) decreased at each challenge: week 1, 7.40 +/- 2.682; month 1, 5.89 +/- 2.431; month 2, 5.09 +/- 2.088; and month 4, 4.85 +/- 1.999. An improvement (vs placebo) of 29.3% for the mean ARTSS ( median, 33.3%) was observed at end point. Furthermore, the induction of grass pollen allergen specific IgGs was associated with clinical response. The most frequent adverse reactions were local: oral pruritus, ear pruritus, and throat irritation. Conclusions: In this ACC study the 300-IR 5-grass-pollen SLIT tablets had a significant effect on rhinoconjunctivitis symptoms (vs placebo) from the first month of treatment onward. (J Allergy Clin Immunol 2009;124:471-7.)	21	98	2009	8	10.1016/j.jaci.2009.06.006	Allergy; Immunology
Indoor molds, bacteria, microbial volatile organic compounds and plasticizers in schools - associations with asthma and respiratory symptoms in pupils. We investigated asthma and atopy in relation to microbial and plasticizer exposure. Pupils in eight primary schools in Uppsala (Sweden) answered a questionnaire, 1014 (68%) participated. Totally, 7.7% reported doctor-diagnosed asthma, 5.9% current asthma, and 12.2% allergy to pollen/pets. Wheeze was reported by 7.8%, 4.5% reported daytime breathlessness, and 2.0% nocturnal breathlessness. Measurements were performed in 23 classrooms (May-June), 74% had < 1000 ppm CO2 indoors. None had visible mold growth or dampness. Mean total microbial volatile organic compound (MVOC) concentration was 423 ng/m(3) indoors and 123 ng/m(3) outdoors. Indoor concentration of TMPD-MIB (2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, Texanol) and TMPD-DIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate, TXIB), two common plasticizers, were 0.89 and 1.64 mu g/m(3), respectively. MVOC and plasticizer concentration were correlated (r = 0.5; P < 0.01). Mold concentration was 360 cfu/m(3) indoors and 980 cfu/m(3) outdoors. At higher indoor concentrations of total MVOC, nocturnal breathlessness (P < 0.01) and doctor-diagnosed asthma (P < 0.05) were more common. Moreover, there were positive associations between nocturnal breathlessness and 3-methylfuran (P < 0.01), 3-methyl-1-butanol (P < 0.05), dimethyldisulfide (P < 0.01), 2-heptanone (P < 0.01), 1-octen-3-ol (P < 0.05), 3-octanone (P < 0.05), TMPD-MIB (P < 0.05), and TMPD-DIB (P < 0.01). TMPD-DIB was positively associated with wheeze (P < 0.05), daytime breathlessness (P < 0.05), doctor-diagnosed asthma (P < 0.05), and current asthma (P < 0.05). In conclusion, exposure to MVOC and plasticizers at school may be a risk factor for asthmatic symptoms in children.. asthma| microbial volatile organic compounds (mvocs)| plasticizer| pupil| respiratory symptoms| school|building-dampness| air-quality| young-children| risk-factors| exposure| environment| schoolchildren| health| formaldehyde| metabolites.	APR-2007	asthma| microbial volatile organic compounds (mvocs)| plasticizer| pupil| respiratory symptoms| school|building-dampness| air-quality| young-children| risk-factors| exposure| environment| schoolchildren| health| formaldehyde| metabolites	Kim, JL; Elfman, L; Mi, Y; Wieslander, G; Smedje, G; Norback, D	Indoor molds, bacteria, microbial volatile organic compounds and plasticizers in schools - associations with asthma and respiratory symptoms in pupils		INDOOR AIR	asthma; microbial volatile organic compounds (MVOCs); plasticizer; pupil; respiratory symptoms; school	BUILDING-DAMPNESS; AIR-QUALITY; YOUNG-CHILDREN; RISK-FACTORS; EXPOSURE; ENVIRONMENT; SCHOOLCHILDREN; HEALTH; FORMALDEHYDE; METABOLITES	We investigated asthma and atopy in relation to microbial and plasticizer exposure. Pupils in eight primary schools in Uppsala (Sweden) answered a questionnaire, 1014 (68%) participated. Totally, 7.7% reported doctor-diagnosed asthma, 5.9% current asthma, and 12.2% allergy to pollen/pets. Wheeze was reported by 7.8%, 4.5% reported daytime breathlessness, and 2.0% nocturnal breathlessness. Measurements were performed in 23 classrooms (May-June), 74% had < 1000 ppm CO2 indoors. None had visible mold growth or dampness. Mean total microbial volatile organic compound (MVOC) concentration was 423 ng/m(3) indoors and 123 ng/m(3) outdoors. Indoor concentration of TMPD-MIB (2,2,4-trimethyl-1,3-pentanediol monoisobutyrate, Texanol) and TMPD-DIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate, TXIB), two common plasticizers, were 0.89 and 1.64 mu g/m(3), respectively. MVOC and plasticizer concentration were correlated (r = 0.5; P < 0.01). Mold concentration was 360 cfu/m(3) indoors and 980 cfu/m(3) outdoors. At higher indoor concentrations of total MVOC, nocturnal breathlessness (P < 0.01) and doctor-diagnosed asthma (P < 0.05) were more common. Moreover, there were positive associations between nocturnal breathlessness and 3-methylfuran (P < 0.01), 3-methyl-1-butanol (P < 0.05), dimethyldisulfide (P < 0.01), 2-heptanone (P < 0.01), 1-octen-3-ol (P < 0.05), 3-octanone (P < 0.05), TMPD-MIB (P < 0.05), and TMPD-DIB (P < 0.01). TMPD-DIB was positively associated with wheeze (P < 0.05), daytime breathlessness (P < 0.05), doctor-diagnosed asthma (P < 0.05), and current asthma (P < 0.05). In conclusion, exposure to MVOC and plasticizers at school may be a risk factor for asthmatic symptoms in children.	61	98	2007	11	10.1111/j.1600-0668.2006.00466.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
Diesel exhaust particles. Diesel motor emission is a complex mixture of hundreds of constituents in either gas or particle form. Diesel particulate matter (DPM) is composed of a center core of elemental carbon and adsorbed organic compounds including PAHs and nitro-PAHs, and small amounts of sulfate, nitrate, metals, and other trace elements. DPM consists of fine particles including a high number of ultrafine particles. These particles are highly respirable and have a large surface area where organics can adsorb easily. Exposure to DPM can cause acute irritation and neurophysiological, respiratory, and asthma-like symptoms and can exacerbate allergenic responses to known allergens. Consistently, lung cancer risk is elevated among workers in occupations where diesel engines have been used. However, quantification of the cancer risk with respect to DPM concentrations is not possible. Furthermore, ambient fine and ultrafine particles, of which DPM is an important component, contribute to cardiopulmonary morbidity and mortality and lung cancer. In conclusion, diesel exhaust poses a cancer risk greater than that of any other air pollutant, as well as causing other short- and long-term health problems. One effective way to effectively reduce emission of DPM is the use of particle traps.. lung-cancer| air-pollution| exposure.	2007	lung-cancer| air-pollution| exposure	Wichmann, HE	Diesel exhaust particles		INHALATION TOXICOLOGY		LUNG-CANCER; AIR-POLLUTION; EXPOSURE	Diesel motor emission is a complex mixture of hundreds of constituents in either gas or particle form. Diesel particulate matter (DPM) is composed of a center core of elemental carbon and adsorbed organic compounds including PAHs and nitro-PAHs, and small amounts of sulfate, nitrate, metals, and other trace elements. DPM consists of fine particles including a high number of ultrafine particles. These particles are highly respirable and have a large surface area where organics can adsorb easily. Exposure to DPM can cause acute irritation and neurophysiological, respiratory, and asthma-like symptoms and can exacerbate allergenic responses to known allergens. Consistently, lung cancer risk is elevated among workers in occupations where diesel engines have been used. However, quantification of the cancer risk with respect to DPM concentrations is not possible. Furthermore, ambient fine and ultrafine particles, of which DPM is an important component, contribute to cardiopulmonary morbidity and mortality and lung cancer. In conclusion, diesel exhaust poses a cancer risk greater than that of any other air pollutant, as well as causing other short- and long-term health problems. One effective way to effectively reduce emission of DPM is the use of particle traps.	11	98	2007	4	10.1080/08958370701498075	Toxicology
Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets. Background: Food allergy is not always correctly diagnosed in children with atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is not without danger. Methods: After admission to our clinic, 11 children with a prolonged cow's milk (CM) elimination diet because of AEDS and sensitization underwent double-blind placebo-controlled food challenge (DBPCFC). Retrospectively, the exposure to CM, sensitization and reactions to accidental ingestion were carefully documented. The DBPCFC was used to evaluate the childrens' current status. Results: Before the elimination period (median 2.3 years; started before the admission) all 11 children with AEDS were sensitized and had ingested CM (four bottle-fed; seven breast-fed without CM diet of the mother) without the development of acute reactions. The diagnosis of CM allergy was not confirmed by DBPCFC previously. After elimination the AEDS had not improved, but nevertheless the diet was continued. During the elimination period, eight of 11 children developed severe acute allergic reactions to CM after accidental ingestion. In evaluation, in our clinic all 11 children experienced acute allergic reactions to CM during DBPCFC. Conclusion: There is a considerable chance of developing acute allergic reactions to CM after elimination in children with AEDS without previous problems after CM intake.. allergic reactions| atopic dermatitis| cow's milk| elimination| tolerance|atopic-dermatitis| food allergy| double-blind| anaphylactic shock| hypersensitivity| challenges| ige| desensitization| infants.	MAR-2006	allergic reactions| atopic dermatitis| cow's milk| elimination| tolerance|atopic-dermatitis| food allergy| double-blind| anaphylactic shock| hypersensitivity| challenges| ige| desensitization| infants	Flinterman, AE; Knulst, AC; Meijer, Y; Bruijnzeel-Koomen, CAFM; Pasmans, SGMA	Acute allergic reactions in children with AEDS after prolonged cow's milk elimination diets		ALLERGY	allergic reactions; atopic dermatitis; cow's milk; elimination; tolerance	ATOPIC-DERMATITIS; FOOD ALLERGY; DOUBLE-BLIND; ANAPHYLACTIC SHOCK; HYPERSENSITIVITY; CHALLENGES; IGE; DESENSITIZATION; INFANTS	Background: Food allergy is not always correctly diagnosed in children with atopic eczema dermatitis syndrome (AEDS) and treatment with an avoidance diet is not without danger. Methods: After admission to our clinic, 11 children with a prolonged cow's milk (CM) elimination diet because of AEDS and sensitization underwent double-blind placebo-controlled food challenge (DBPCFC). Retrospectively, the exposure to CM, sensitization and reactions to accidental ingestion were carefully documented. The DBPCFC was used to evaluate the childrens' current status. Results: Before the elimination period (median 2.3 years; started before the admission) all 11 children with AEDS were sensitized and had ingested CM (four bottle-fed; seven breast-fed without CM diet of the mother) without the development of acute reactions. The diagnosis of CM allergy was not confirmed by DBPCFC previously. After elimination the AEDS had not improved, but nevertheless the diet was continued. During the elimination period, eight of 11 children developed severe acute allergic reactions to CM after accidental ingestion. In evaluation, in our clinic all 11 children experienced acute allergic reactions to CM during DBPCFC. Conclusion: There is a considerable chance of developing acute allergic reactions to CM after elimination in children with AEDS without previous problems after CM intake.	29	98	2006	5	10.1111/j.1398-9995.2006.01018.x	Allergy; Immunology
Multicenter study of emergency department visits for insect sting allergies. Background: An earlier study of food-related anaphylaxis in the emergency department (ED) suggested low concordance with national guidelines for anaphylaxis management. Objective: To extend these findings, we performed a chart review study to describe current ED management of insect sting allergy. Methods: The Multicenter Airway Research Collaboration performed a chart review study in 15 North American EDs. Investigators reviewed 617 charts of patients with insect sting allergy. Patients were identified by using International Classification of Diseases, 9th Revision, codes 989.5 (toxic effect of venom), 995.0 (other anaphylactic shock), and 995.3 (allergy, unspecified). Results: The cohort was 42% female and 61% white, with a mean age of 36 +/- 19 years. In this cohort, 58% had local reactions, 11% had mild systemic reactions, and 31% had anaphylactic reactions, as defined by multisystem organ involvement or hypotension. Among patients with systemic reactions (mild or anaphylaxis), most (75%) were stung within 6 hours of ED arrival. While in the ED, 69% of systemic reaction patients received antihistamines, 50% systemic corticosteroids, and 12% epinephrine. Almost all systemic reaction patients (95%) were discharged to home. At ED discharge, 27% (95% CI, 22% to 33%) of systemic reaction patients received a prescription for self-injectable epinephrine. Only 20% (95% CI, 15% to 26%) had documentation of referral to an allergist. Conclusions: Although guidelines suggest specific approaches for the emergency management of insect sting allergy, concordance with these guidelines appears low in patients with a severe insect sting reaction.. insect sting allergy| emergency department| epinephrine| referral to allergist|united-states| anaphylaxis| epidemiology| hypersensitivity| hymenoptera| management| sensitivity| population| severity| disease.	SEP-2005	insect sting allergy| emergency department| epinephrine| referral to allergist|united-states| anaphylaxis| epidemiology| hypersensitivity| hymenoptera| management| sensitivity| population| severity| disease	Clark, S; Long, AA; Gaeta, TJ; Camargo, CA	Multicenter study of emergency department visits for insect sting allergies		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	insect sting allergy; emergency department; epinephrine; referral to allergist	UNITED-STATES; ANAPHYLAXIS; EPIDEMIOLOGY; HYPERSENSITIVITY; HYMENOPTERA; MANAGEMENT; SENSITIVITY; POPULATION; SEVERITY; DISEASE	Background: An earlier study of food-related anaphylaxis in the emergency department (ED) suggested low concordance with national guidelines for anaphylaxis management. Objective: To extend these findings, we performed a chart review study to describe current ED management of insect sting allergy. Methods: The Multicenter Airway Research Collaboration performed a chart review study in 15 North American EDs. Investigators reviewed 617 charts of patients with insect sting allergy. Patients were identified by using International Classification of Diseases, 9th Revision, codes 989.5 (toxic effect of venom), 995.0 (other anaphylactic shock), and 995.3 (allergy, unspecified). Results: The cohort was 42% female and 61% white, with a mean age of 36 +/- 19 years. In this cohort, 58% had local reactions, 11% had mild systemic reactions, and 31% had anaphylactic reactions, as defined by multisystem organ involvement or hypotension. Among patients with systemic reactions (mild or anaphylaxis), most (75%) were stung within 6 hours of ED arrival. While in the ED, 69% of systemic reaction patients received antihistamines, 50% systemic corticosteroids, and 12% epinephrine. Almost all systemic reaction patients (95%) were discharged to home. At ED discharge, 27% (95% CI, 22% to 33%) of systemic reaction patients received a prescription for self-injectable epinephrine. Only 20% (95% CI, 15% to 26%) had documentation of referral to an allergist. Conclusions: Although guidelines suggest specific approaches for the emergency management of insect sting allergy, concordance with these guidelines appears low in patients with a severe insect sting reaction.	30	98	2005	7	10.1016/j.jaci.2005.06.026	Allergy; Immunology
Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation. Matrix metalloproteinases (MMPs) are involved in inflammatory reaction, including asthma-related airway inflammation. MMP-8, mainly produced by neutrophils, has recently been reported to be increased in the bronchoalveolar lavage fluid (BALF) from asthmatic patients. To evaluate the role of MMP-8 in asthma, we measured MMP-8 expression in lung tissue in an OVAsensitized mouse model of asthma and addressed the effect of MMP-8 deletion on allergen-induced bronchial inflammation. MMP-8 production was increased in lungs from C57BL/6 mice exposed to allergens. After allergen exposure, MMP-8-1-mice developed an airway inflammation characterized by an increased neutrophilic inflammation in BALF and an increased neutrophilic and eosinophilic infiltration in the airway walls. MMP-8 deficiency was associated with increased levels of IL-4 and antiOVA IgE and IgG1 in BALF and serum, respectively. Although allergen exposure induced an enhancement of LPS-induced CXC chemokine, KC, and MIP-2 levels in BALF and lung parenchyma, no difference was observed between the two genotypes. Inflammatory cell apoptosis was reduced in the lungs from MMP-8(-/-) mice. For the first time, our study evidences an important role of MMP-8 in the control of neutrophilic and eosinophilic infiltration during allergen-induced lung inflammation, and demonstrates that the anti-inflammatory effect of MMP-8 is partly due to a regulation of inflammatory cell apoptosis.. human neutrophil collagenase| bronchoalveolar lavage fluid| asthmatic-patients| mmp-8 expression| tissue inhibitor| epithelial-cells| matrix-metalloproteinase-9| disease| cancer| hyperresponsiveness.	AUG 15-2005	human neutrophil collagenase| bronchoalveolar lavage fluid| asthmatic-patients| mmp-8 expression| tissue inhibitor| epithelial-cells| matrix-metalloproteinase-9| disease| cancer| hyperresponsiveness	Gueders, MM; Balbin, M; Rocks, N; Foidart, JM; Gosset, P; Louis, R; Shapiro, S; Lopez-Otin, C; Noel, W; Cataldo, DD	Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation		JOURNAL OF IMMUNOLOGY		HUMAN NEUTROPHIL COLLAGENASE; BRONCHOALVEOLAR LAVAGE FLUID; ASTHMATIC-PATIENTS; MMP-8 EXPRESSION; TISSUE INHIBITOR; EPITHELIAL-CELLS; MATRIX-METALLOPROTEINASE-9; DISEASE; CANCER; HYPERRESPONSIVENESS	Matrix metalloproteinases (MMPs) are involved in inflammatory reaction, including asthma-related airway inflammation. MMP-8, mainly produced by neutrophils, has recently been reported to be increased in the bronchoalveolar lavage fluid (BALF) from asthmatic patients. To evaluate the role of MMP-8 in asthma, we measured MMP-8 expression in lung tissue in an OVAsensitized mouse model of asthma and addressed the effect of MMP-8 deletion on allergen-induced bronchial inflammation. MMP-8 production was increased in lungs from C57BL/6 mice exposed to allergens. After allergen exposure, MMP-8-1-mice developed an airway inflammation characterized by an increased neutrophilic inflammation in BALF and an increased neutrophilic and eosinophilic infiltration in the airway walls. MMP-8 deficiency was associated with increased levels of IL-4 and antiOVA IgE and IgG1 in BALF and serum, respectively. Although allergen exposure induced an enhancement of LPS-induced CXC chemokine, KC, and MIP-2 levels in BALF and lung parenchyma, no difference was observed between the two genotypes. Inflammatory cell apoptosis was reduced in the lungs from MMP-8(-/-) mice. For the first time, our study evidences an important role of MMP-8 in the control of neutrophilic and eosinophilic infiltration during allergen-induced lung inflammation, and demonstrates that the anti-inflammatory effect of MMP-8 is partly due to a regulation of inflammatory cell apoptosis.	41	98	2005	9		Immunology
"Air pollution and infant health: What can we learn from California's recent experience?. We examine the impact of air pollution on infant death in California over the 1990s. Our work offers several innovations: first, most previous studies examine populations subject to far greater levels of pollution. Second, many studies examine a single pollutant in isolation. We examine three ""criteria"" pollutants in a common framework. Third, we use rich individual-level data and pollution measured at the weekly level. Our most novel finding is a significant effect of CO on infant mortality: we find that reductions in carbon monoxide over the 1990s saved approximately 1000 infant lives in California.. low-birth-weight| utah valley| southern california| childhood asthma| pm(10) pollution| children born| mortality| ambient| exposure| quality."	AUG-2005	low-birth-weight| utah valley| southern california| childhood asthma| pm(10) pollution| children born| mortality| ambient| exposure| quality	Currie, J; Neidell, M	Air pollution and infant health: What can we learn from California's recent experience?		QUARTERLY JOURNAL OF ECONOMICS		LOW-BIRTH-WEIGHT; UTAH VALLEY; SOUTHERN CALIFORNIA; CHILDHOOD ASTHMA; PM(10) POLLUTION; CHILDREN BORN; MORTALITY; AMBIENT; EXPOSURE; QUALITY	"We examine the impact of air pollution on infant death in California over the 1990s. Our work offers several innovations: first, most previous studies examine populations subject to far greater levels of pollution. Second, many studies examine a single pollutant in isolation. We examine three ""criteria"" pollutants in a common framework. Third, we use rich individual-level data and pollution measured at the weekly level. Our most novel finding is a significant effect of CO on infant mortality: we find that reductions in carbon monoxide over the 1990s saved approximately 1000 infant lives in California."	39	98	2005	28	10.1093/qje/120.3.1003	Business & Economics
"Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders. In the rich, developed parts of the world there has been a steady and simultaneous increase in at least three groups of disease: (1) allergies, (2) inflammatory bowel diseases (IBD; e.g. Crohn's disease and ulcerative colitis) and (3) autoimmunity (e.g. type 1 diabetes and multiple sclerosis). Because the medical world is so compartmentalised it was some time before the connection between these increases was noticed and understood. There is now evidence that the simultaneous increase in these diseases of immunodysregulation is at least partly attributable to malfunction of regulatory T cells (Treg). This paper provides an overview of relevant work in each of these fields of medicine (though with emphasis on the allergic disorders), and concludes that the increasing failure of Treg is a consequence of diminished exposure to certain micro-organisms that are ""old friends"", because of their continuous presence throughout mammalian evolution. These organisms, which include saprophytic mycobacteria, helminths and lactobacilli, are recognised by the innate immune system as harmless, and as adjuvants for Treg induction. Polymorphisms of components of the innate immune system such as TLR2 and NOD2 appear to define subsets of the population that will develop immunoregulatory disorders when living in the modern environment. A further role of the ""old friends"" and of the Treg that they induce might be to maintain the levels of regulatory IL-10 secreting macrophages and antigen-presenting cells, which are depleted in asthma and Crohn's disease. These concepts are leading to novel therapies based on harmless organisms or their components. Phase I/II clinical trials have yielded some statistically significant results, and phase II trials are in progress.. regulatory t cell| allergies| regulatory antigen-presenting cell| innate immunity| autoimmunity|regulatory t-cells| monoclonal-antibody treatment| inflammatory-bowel-disease| toll-like receptors| in-vivo| multiple-sclerosis| interferon-gamma| allergic-asthma| dendritic cells| airway hyperreactivity."	FEB-2004	regulatory t cell| allergies| regulatory antigen-presenting cell| innate immunity| autoimmunity|regulatory t-cells| monoclonal-antibody treatment| inflammatory-bowel-disease| toll-like receptors| in-vivo| multiple-sclerosis| interferon-gamma| allergic-asthma| dendritic cells| airway hyperreactivity	Rook, GAW; Adams, V; Hunt, J; Palmer, R; Martinelli, R; Brunet, LR	Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders		SPRINGER SEMINARS IN IMMUNOPATHOLOGY	regulatory T cell; allergies; regulatory antigen-presenting cell; innate immunity; autoimmunity	REGULATORY T-CELLS; MONOCLONAL-ANTIBODY TREATMENT; INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTORS; IN-VIVO; MULTIPLE-SCLEROSIS; INTERFERON-GAMMA; ALLERGIC-ASTHMA; DENDRITIC CELLS; AIRWAY HYPERREACTIVITY	"In the rich, developed parts of the world there has been a steady and simultaneous increase in at least three groups of disease: (1) allergies, (2) inflammatory bowel diseases (IBD; e.g. Crohn's disease and ulcerative colitis) and (3) autoimmunity (e.g. type 1 diabetes and multiple sclerosis). Because the medical world is so compartmentalised it was some time before the connection between these increases was noticed and understood. There is now evidence that the simultaneous increase in these diseases of immunodysregulation is at least partly attributable to malfunction of regulatory T cells (Treg). This paper provides an overview of relevant work in each of these fields of medicine (though with emphasis on the allergic disorders), and concludes that the increasing failure of Treg is a consequence of diminished exposure to certain micro-organisms that are ""old friends"", because of their continuous presence throughout mammalian evolution. These organisms, which include saprophytic mycobacteria, helminths and lactobacilli, are recognised by the innate immune system as harmless, and as adjuvants for Treg induction. Polymorphisms of components of the innate immune system such as TLR2 and NOD2 appear to define subsets of the population that will develop immunoregulatory disorders when living in the modern environment. A further role of the ""old friends"" and of the Treg that they induce might be to maintain the levels of regulatory IL-10 secreting macrophages and antigen-presenting cells, which are depleted in asthma and Crohn's disease. These concepts are leading to novel therapies based on harmless organisms or their components. Phase I/II clinical trials have yielded some statistically significant results, and phase II trials are in progress."	106	98	2004	19	10.1007/s00281-003-0148-9	Immunology; Pathology
Do mouse models of allergic asthma mimic clinical disease?. Experimental mouse models of allergic asthma established almost 10 years ago offered new opportunities to study disease pathogenesis and to develop new therapeutics. These models focused on the factors governing the allergic immune response, on modeling clinical behavior of allergic asthma, and led to insights into pulmonary pathophysiology. Although mouse models rarely completely reproduce all the features of human disease, after sensitization and respiratory tract challenges with antigen, wild-type mice develop a clinical syndrome that closely resembles allergic asthma, characterized by eosinophilic lung inflammation, airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and eventually, airway remodeling. There are, however, differences between mouse and human physiology that threaten to limit the value of mouse models. Three examples of such differences relate to both clinical manifestations of disease and underlying pathogenesis. First, in contrast to patients who have increased methacholine-induced AHR even when they are symptom-free, mice exhibit only transient methacholine-induced AHR following allergen exposure. Second, chronic allergen exposure in patients leads to chronic allergic asthma, whereas repeated exposures in sensitized mice causes suppression of disease. Third, IgE and mast cells, in humans, mediate early- and late-phase allergic responses, though both are unnecessary for the generation of allergic asthma in mice. Taken together, these observations suggest that mouse models of allergic asthma are not exact replicas of human disease and thus, question the validity of these models. However, observations from mouse models of allergic asthma support many existing paradigms, although some novel discoveries in mice have yet to be verified in patients. This review presents an overview of the clinical aspects of disease in mouse models of allergic asthma emphasizing ( 1) the factors influencing the pathophysiological responses during the initiation and perpetuation of disease, ( 2) the utility of mouse models for studying clinical manifestations of disease, and ( 3) the applicability of mouse models for testing new treatments for allergic asthma. Copyright (C) 2004 S. Karger AG, Basel.. allergic asthma, pathophysiology| allergic asthma, pathology| allergic asthmam, therapy| immunoglobulin e| eosinophilic lung inflammation| immunological memory| th2 cells| airway resistance| allergens, administration and dosage| mice, congenic|induced airway hyperreactivity| cell-deficient mice| house-dust mite| tract dendritic cells| regulatory t-cells| murine strain differences| diesel exhaust particles| receptor transgenic mice| birch pollen allergen| toll-like receptor-4.	2004	allergic asthma, pathophysiology| allergic asthma, pathology| allergic asthmam, therapy| immunoglobulin e| eosinophilic lung inflammation| immunological memory| th2 cells| airway resistance| allergens, administration and dosage| mice, congenic|induced airway hyperreactivity| cell-deficient mice| house-dust mite| tract dendritic cells| regulatory t-cells| murine strain differences| diesel exhaust particles| receptor transgenic mice| birch pollen allergen| toll-like receptor-4	Epstein, MM	Do mouse models of allergic asthma mimic clinical disease?		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	allergic asthma, pathophysiology; allergic asthma, pathology; allergic asthmam, therapy; immunoglobulin E; eosinophilic lung inflammation; immunological memory; Th2 cells; airway resistance; allergens, administration and dosage; mice, congenic	INDUCED AIRWAY HYPERREACTIVITY; CELL-DEFICIENT MICE; HOUSE-DUST MITE; TRACT DENDRITIC CELLS; REGULATORY T-CELLS; MURINE STRAIN DIFFERENCES; DIESEL EXHAUST PARTICLES; RECEPTOR TRANSGENIC MICE; BIRCH POLLEN ALLERGEN; TOLL-LIKE RECEPTOR-4	Experimental mouse models of allergic asthma established almost 10 years ago offered new opportunities to study disease pathogenesis and to develop new therapeutics. These models focused on the factors governing the allergic immune response, on modeling clinical behavior of allergic asthma, and led to insights into pulmonary pathophysiology. Although mouse models rarely completely reproduce all the features of human disease, after sensitization and respiratory tract challenges with antigen, wild-type mice develop a clinical syndrome that closely resembles allergic asthma, characterized by eosinophilic lung inflammation, airway hyperresponsiveness (AHR), increased IgE, mucus hypersecretion, and eventually, airway remodeling. There are, however, differences between mouse and human physiology that threaten to limit the value of mouse models. Three examples of such differences relate to both clinical manifestations of disease and underlying pathogenesis. First, in contrast to patients who have increased methacholine-induced AHR even when they are symptom-free, mice exhibit only transient methacholine-induced AHR following allergen exposure. Second, chronic allergen exposure in patients leads to chronic allergic asthma, whereas repeated exposures in sensitized mice causes suppression of disease. Third, IgE and mast cells, in humans, mediate early- and late-phase allergic responses, though both are unnecessary for the generation of allergic asthma in mice. Taken together, these observations suggest that mouse models of allergic asthma are not exact replicas of human disease and thus, question the validity of these models. However, observations from mouse models of allergic asthma support many existing paradigms, although some novel discoveries in mice have yet to be verified in patients. This review presents an overview of the clinical aspects of disease in mouse models of allergic asthma emphasizing ( 1) the factors influencing the pathophysiological responses during the initiation and perpetuation of disease, ( 2) the utility of mouse models for studying clinical manifestations of disease, and ( 3) the applicability of mouse models for testing new treatments for allergic asthma. Copyright (C) 2004 S. Karger AG, Basel.	208	98	2004	17	10.1159/000076131	Allergy; Immunology
Removal of indoor pollutants under UV irradiation by a composite TiO2-zeolite sheet prepared using a papermaking technique. Toluene and formaldehyde are malodorous and cause indoor pollution. These materials have received much attention as hazardous and malodorous substances. It is well known that long-term exposure to even fairly low levels of toluene and formaldehyde brings about the risk of asthma, and eczema. In this study, a composite TiO2-zeolite (ZE) sheet prepared using a papermaking technique was applied to remove toluene and formaldehyde under UV irradiation. The optimum composition of the TiO2 (Ti)-ZE sheet was studied in detail with regard to the effective removal of various indoor pollutants. Gaseous toluene and formaldehyde were removed by a composite TiO2-ZE sheet with different efficiencies depending upon the ratio of Ti/ZE in the composite sheet. The composite sheets could decompose formaldehyde and toluene repeatedly after being recharged. It was shown that the sheets are potentially applicable as highly functional materials to be placed on walls and ceilings of houses for the removal of various indoor pollutants. (C) 2002 Elsevier Science Ltd. All rights reserved.. photocatalyst| adsorbent| composite tio2-zeolite sheet| papermaking technique| indoor pollution|volatile organic-compounds| photocatalytic oxidation| incremental reactivities| film photocatalyst| air-quality| tio2| zeolite| illumination| acetaldehyde| degradation.	JAN-2003	photocatalyst| adsorbent| composite tio2-zeolite sheet| papermaking technique| indoor pollution|volatile organic-compounds| photocatalytic oxidation| incremental reactivities| film photocatalyst| air-quality| tio2| zeolite| illumination| acetaldehyde| degradation	Ichiura, H; Kitaoka, T; Tanaka, H	Removal of indoor pollutants under UV irradiation by a composite TiO2-zeolite sheet prepared using a papermaking technique		CHEMOSPHERE	photocatalyst; adsorbent; composite TiO2-zeolite sheet; papermaking technique; indoor pollution	VOLATILE ORGANIC-COMPOUNDS; PHOTOCATALYTIC OXIDATION; INCREMENTAL REACTIVITIES; FILM PHOTOCATALYST; AIR-QUALITY; TIO2; ZEOLITE; ILLUMINATION; ACETALDEHYDE; DEGRADATION	Toluene and formaldehyde are malodorous and cause indoor pollution. These materials have received much attention as hazardous and malodorous substances. It is well known that long-term exposure to even fairly low levels of toluene and formaldehyde brings about the risk of asthma, and eczema. In this study, a composite TiO2-zeolite (ZE) sheet prepared using a papermaking technique was applied to remove toluene and formaldehyde under UV irradiation. The optimum composition of the TiO2 (Ti)-ZE sheet was studied in detail with regard to the effective removal of various indoor pollutants. Gaseous toluene and formaldehyde were removed by a composite TiO2-ZE sheet with different efficiencies depending upon the ratio of Ti/ZE in the composite sheet. The composite sheets could decompose formaldehyde and toluene repeatedly after being recharged. It was shown that the sheets are potentially applicable as highly functional materials to be placed on walls and ceilings of houses for the removal of various indoor pollutants. (C) 2002 Elsevier Science Ltd. All rights reserved.	23	98	2003	5	10.1016/S0045-6535(02)00604-5	Environmental Sciences & Ecology
Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31(hi)Ly6C(neg) bone marrow precursors in a mouse model of asthma. Airway dendritic cells (DCs) are held responsible for inducing sensitization to Inhaled antigen, leading to eosinophilic airway inflammation, typical of asthma. However, less information is available about the role of these cells in ongoing inflammation. In a mouse model of asthma, sensitization to ovalbumin (OVA) was induced by intratracheal injection of myeloid OVA-pulsed DCs. Upon OVA aerosol challenge and induction of eosinophilic airway inflammation in sensitized mice, there was a time-dependent and almost 100-fold increase In the number of MHCII+ CD11b(+) CD11c(+) endogenous air-way DCs as well as CD11b(+) blood DCs. The mechanism of this increase was studied. Adoptive transfer experiments demonstrated that accumulation of airway DCs was not due to reduced migration to the mediastinal lymph nodes. Rather, the massive increase in airway and lymph node DCs was supported by an almost 3-fold expansion of myeloid CD31(hi)Ly-6C(neg) hematopoietic precursor cells in the bone marrow (BM). There was no change in any of the other 5 populations revealed by CD31/Ly-6C staining. When these CD31(hi)Ly-6C(neg) BM precursors were sorted and grown in granulocyte macro-phage-colony-stimulating factor, they differentiated into MHCII+ CD11c(+) DCs. The same CD31(hi)Ly-6C(neg) precursors also expressed the eotaxin receptor CCR3 and differentiated into eosinophils when grown in interleukin 5. Serum levels of eotaxin were doubled in mice with inflammation. These findings in an animal model of asthma suggest that the BM increases its output of myeloid precursors to meet the enhanced demand for DCs and eosinophils in inflamed airways. (C) 2002 by The American Society of Hematology.. colony-stimulating factor| lung inflammation| inhaled antigen| murine model| lymph-nodes| er-mp12| mice| eosinophilia| responses| challenge.	NOV 15-2002	colony-stimulating factor| lung inflammation| inhaled antigen| murine model| lymph-nodes| er-mp12| mice| eosinophilia| responses| challenge	van Rijt, LS; Prins, JB; Leenen, PJM; Thielemans, K; de Vries, VC; Hoogsteden, HC; Lambrecht, BN	Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31(hi)Ly6C(neg) bone marrow precursors in a mouse model of asthma		BLOOD		COLONY-STIMULATING FACTOR; LUNG INFLAMMATION; INHALED ANTIGEN; MURINE MODEL; LYMPH-NODES; ER-MP12; MICE; EOSINOPHILIA; RESPONSES; CHALLENGE	Airway dendritic cells (DCs) are held responsible for inducing sensitization to Inhaled antigen, leading to eosinophilic airway inflammation, typical of asthma. However, less information is available about the role of these cells in ongoing inflammation. In a mouse model of asthma, sensitization to ovalbumin (OVA) was induced by intratracheal injection of myeloid OVA-pulsed DCs. Upon OVA aerosol challenge and induction of eosinophilic airway inflammation in sensitized mice, there was a time-dependent and almost 100-fold increase In the number of MHCII+ CD11b(+) CD11c(+) endogenous air-way DCs as well as CD11b(+) blood DCs. The mechanism of this increase was studied. Adoptive transfer experiments demonstrated that accumulation of airway DCs was not due to reduced migration to the mediastinal lymph nodes. Rather, the massive increase in airway and lymph node DCs was supported by an almost 3-fold expansion of myeloid CD31(hi)Ly-6C(neg) hematopoietic precursor cells in the bone marrow (BM). There was no change in any of the other 5 populations revealed by CD31/Ly-6C staining. When these CD31(hi)Ly-6C(neg) BM precursors were sorted and grown in granulocyte macro-phage-colony-stimulating factor, they differentiated into MHCII+ CD11c(+) DCs. The same CD31(hi)Ly-6C(neg) precursors also expressed the eotaxin receptor CCR3 and differentiated into eosinophils when grown in interleukin 5. Serum levels of eotaxin were doubled in mice with inflammation. These findings in an animal model of asthma suggest that the BM increases its output of myeloid precursors to meet the enhanced demand for DCs and eosinophils in inflamed airways. (C) 2002 by The American Society of Hematology.	38	98	2002	9	10.1182/blood-2002-03-0673	Hematology
Effects of meteorological conditions on spore plumes. Fungal spores are an ever-present component of the atmosphere, and have long been known to trigger asthma and hay fever symptoms in sensitive individuals. The atmosphere around Tulsa has been monitored for airborne spores and pollen with Burkard spore traps at several sampling stations. This study involved the examination of the hourly spore concentrations on days that had average daily concentrations near 50,000 spores/m(3) or greater. Hourly concentrations of Cladosporium, Alternaria, Epicoccum, Curvularia, Pithomyces, Drechslera, smut spores, ascospores, basidiospores, other, and total spores were determined on 4 days at three sites and then correlated with hourly meteorological data including temperature, rainfall, wind speed, dew point, air pressure, and wind direction. On each of these days there was a spore plume, a phenomenon in which spore concentrations increased dramatically over a very short period of time. Spore plumes generally occurred near midday, and concentrations were seen to increase from lows around 20,000 total spores/m(3) to highs over 170,000 total spores/m(3) in 2 h. Multiple regression analysis of the data indicated that increases in temperature, dew point, and air pressure correlated with the increase in spore concentrations, but no single weather variable predicted the appearance of a spore plume. The proper combination of changes in these meteorological parameters that result in a spore plume may be due to the changing weather conditions associated with thunderstorms, as on 3 of the 4 days when spore plumes occurred there were thunderstorms later that evening. The occurrence of spore plumes may have clinical significance, because other studies have shown that sensitization to certain spore types can occur during exposure to high spore concentrations.. spore plumes| fungal spores| asthma| hay fever| meteorological conditions|alternaria-alternata| risk factor| asthma| weather.	AUG-2002	spore plumes| fungal spores| asthma| hay fever| meteorological conditions|alternaria-alternata| risk factor| asthma| weather	Burch, M; Levetin, E	Effects of meteorological conditions on spore plumes		INTERNATIONAL JOURNAL OF BIOMETEOROLOGY	spore plumes; fungal spores; asthma; hay fever; meteorological conditions	ALTERNARIA-ALTERNATA; RISK FACTOR; ASTHMA; WEATHER	Fungal spores are an ever-present component of the atmosphere, and have long been known to trigger asthma and hay fever symptoms in sensitive individuals. The atmosphere around Tulsa has been monitored for airborne spores and pollen with Burkard spore traps at several sampling stations. This study involved the examination of the hourly spore concentrations on days that had average daily concentrations near 50,000 spores/m(3) or greater. Hourly concentrations of Cladosporium, Alternaria, Epicoccum, Curvularia, Pithomyces, Drechslera, smut spores, ascospores, basidiospores, other, and total spores were determined on 4 days at three sites and then correlated with hourly meteorological data including temperature, rainfall, wind speed, dew point, air pressure, and wind direction. On each of these days there was a spore plume, a phenomenon in which spore concentrations increased dramatically over a very short period of time. Spore plumes generally occurred near midday, and concentrations were seen to increase from lows around 20,000 total spores/m(3) to highs over 170,000 total spores/m(3) in 2 h. Multiple regression analysis of the data indicated that increases in temperature, dew point, and air pressure correlated with the increase in spore concentrations, but no single weather variable predicted the appearance of a spore plume. The proper combination of changes in these meteorological parameters that result in a spore plume may be due to the changing weather conditions associated with thunderstorms, as on 3 of the 4 days when spore plumes occurred there were thunderstorms later that evening. The occurrence of spore plumes may have clinical significance, because other studies have shown that sensitization to certain spore types can occur during exposure to high spore concentrations.	16	98	2002	11	10.1007/s00484-002-0127-1	Biophysics; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences; Physiology
The biology of dust mites and the remediation of mite allergens in allergic disease. In most temperate humid areas of the world, house dust mites are a major source of multiple allergens in house dust Mite allergens sensitize and induce perennial rhinitis, asthma, or atopic dermatitis in a large portion of patients with allergic disease. There is convincing evidence that avoidance of mite allergen can effectively reduce allergic symptoms, Patients can be moved to a mite allergen-free environment, or mite and mite allergen abatement can be performed to reduce exposure in existing residences. Some knowledge of the biology of house dust mites is essential to understand the basis of the recommendations for reducing mites and mite allergens in homes and to appreciate the difficulty of eliminating house dust mites and mite allergens from homes. This article reviews key aspects of the biology of dust mites, the properties of mite allergens, recommendations for reducing mite and mite allergen concentrations in homes, and practical recommendations for treatment.. house dust mite abatement| allergen remediation| mite allergy| dust mite biology|dermatophagoides-pteronyssinus acari| solidified benzyl benzoate| house-dust| farinae acari| bronchial hyperreactivity| relative humidities| euroglyphus-maynei| asthmatic-children| bedding encasement| seasonal-variation.	MAR-2001	house dust mite abatement| allergen remediation| mite allergy| dust mite biology|dermatophagoides-pteronyssinus acari| solidified benzyl benzoate| house-dust| farinae acari| bronchial hyperreactivity| relative humidities| euroglyphus-maynei| asthmatic-children| bedding encasement| seasonal-variation	Arlian, LG; Platts-Mills, TAE	The biology of dust mites and the remediation of mite allergens in allergic disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	house dust mite abatement; allergen remediation; mite allergy; dust mite biology	DERMATOPHAGOIDES-PTERONYSSINUS ACARI; SOLIDIFIED BENZYL BENZOATE; HOUSE-DUST; FARINAE ACARI; BRONCHIAL HYPERREACTIVITY; RELATIVE HUMIDITIES; EUROGLYPHUS-MAYNEI; ASTHMATIC-CHILDREN; BEDDING ENCASEMENT; SEASONAL-VARIATION	In most temperate humid areas of the world, house dust mites are a major source of multiple allergens in house dust Mite allergens sensitize and induce perennial rhinitis, asthma, or atopic dermatitis in a large portion of patients with allergic disease. There is convincing evidence that avoidance of mite allergen can effectively reduce allergic symptoms, Patients can be moved to a mite allergen-free environment, or mite and mite allergen abatement can be performed to reduce exposure in existing residences. Some knowledge of the biology of house dust mites is essential to understand the basis of the recommendations for reducing mites and mite allergens in homes and to appreciate the difficulty of eliminating house dust mites and mite allergens from homes. This article reviews key aspects of the biology of dust mites, the properties of mite allergens, recommendations for reducing mite and mite allergen concentrations in homes, and practical recommendations for treatment.	96	98	2001	8	10.1067/mai.2001.113670	Allergy; Immunology
Sampling and analysis of airborne particulate matter and aerosols using in-needle trap and SPME fiber devices. A needle trap device (NTD) and commercial poly(dimethylsiloxane) (PDMS) 7-mum film thickness solid-phase microextraction (SPME) fibers were used for the sampling and analysis of aerosols and airborne particulate matter (PM) from an inhaler-administered drag, spray insect repellant, and tailpipe diesel exhaust. The NTD consisted of a 0.53-mm o.d. stainless steel needle having 5 mm of quartz wool packing section near the needle tip. Samples were collected by drawing air across the NTD with a Luer-tip syringe or via direct exposure of the SPME fiber. The mass loading of PM was varied by adjusting the volume of air pulled through the NTD or by varying the sampling time for the SPME fiber. The air volumes ranged from 0.1 to 50 mt, and sampling times varied from 10 s to 16 min; Particulates were either trapped on the needle packing or sorbed onto the SPME fiber, The devices were introduced to a chromatograph/mass spectrometer (GC/MS) injector for 5 min desorption, In the case of the NTD, 10 muL of clean air was delivered by a gas-tight syringe to aid the introduction of desorbed analytes. The compounds sorbed onto particles extracted by the SPME fiber or trapped in the needle device were desorbed in the injector and no carry-over was observed, Both devices performed well in extracting airborne polycyclic aromatic hydrocarbons: (PAHs) in diesel exhaust, triamcinolone acetonide in a dose of asthma drug and BEET in a dose of insect repellant spray, Results suggest that the NTDs and PDMS 7-mum fibers can be used for airborne particulate sampling and analysis, providing a simple, fast, reusable, and cost-effective screening tool, The advantage of the SPME fiber is the open-bed geometry allowing spectroscopic investigations of particulates; for example, with Raman microspectroscopy.. solid-phase microextraction| performance liquid-chromatography| polycyclic aromatic-hydrocarbons| capillary-electrophoresis| gas-chromatography| air| spectroscopy| separation.	JAN 1-2001	solid-phase microextraction| performance liquid-chromatography| polycyclic aromatic-hydrocarbons| capillary-electrophoresis| gas-chromatography| air| spectroscopy| separation	Koziel, JA; Odziemkowski, M; Pawliszyn, J	Sampling and analysis of airborne particulate matter and aerosols using in-needle trap and SPME fiber devices		ANALYTICAL CHEMISTRY		SOLID-PHASE MICROEXTRACTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYCYCLIC AROMATIC-HYDROCARBONS; CAPILLARY-ELECTROPHORESIS; GAS-CHROMATOGRAPHY; AIR; SPECTROSCOPY; SEPARATION	A needle trap device (NTD) and commercial poly(dimethylsiloxane) (PDMS) 7-mum film thickness solid-phase microextraction (SPME) fibers were used for the sampling and analysis of aerosols and airborne particulate matter (PM) from an inhaler-administered drag, spray insect repellant, and tailpipe diesel exhaust. The NTD consisted of a 0.53-mm o.d. stainless steel needle having 5 mm of quartz wool packing section near the needle tip. Samples were collected by drawing air across the NTD with a Luer-tip syringe or via direct exposure of the SPME fiber. The mass loading of PM was varied by adjusting the volume of air pulled through the NTD or by varying the sampling time for the SPME fiber. The air volumes ranged from 0.1 to 50 mt, and sampling times varied from 10 s to 16 min; Particulates were either trapped on the needle packing or sorbed onto the SPME fiber, The devices were introduced to a chromatograph/mass spectrometer (GC/MS) injector for 5 min desorption, In the case of the NTD, 10 muL of clean air was delivered by a gas-tight syringe to aid the introduction of desorbed analytes. The compounds sorbed onto particles extracted by the SPME fiber or trapped in the needle device were desorbed in the injector and no carry-over was observed, Both devices performed well in extracting airborne polycyclic aromatic hydrocarbons: (PAHs) in diesel exhaust, triamcinolone acetonide in a dose of asthma drug and BEET in a dose of insect repellant spray, Results suggest that the NTDs and PDMS 7-mum fibers can be used for airborne particulate sampling and analysis, providing a simple, fast, reusable, and cost-effective screening tool, The advantage of the SPME fiber is the open-bed geometry allowing spectroscopic investigations of particulates; for example, with Raman microspectroscopy.	29	98	2001	8	10.1021/ac000835s	Chemistry
Lung microbiota promotes tolerance to allergens in neonates via PD-L1. Epidemiological data point toward a critical period in early life during which environmental cues can set an individual on a trajectory toward respiratory health or disease(1-8). The neonatal immune system matures during this period(9), although little is known about the signals that lead to its maturation. Here we report that the formation of the lung microbiota is a key parameter in this process. Immediately following birth, neonatal mice were prone to develop exaggerated airway eosinophilia, release type 2 helper T cell cytokines and exhibit airway hyper-responsiveness following exposure to house dust mite allergens, even though their lungs harbored high numbers of natural CD4(+)Foxp3(+)CD25(+)Helios(+) regulatory T (T-reg cells. During the first 2 weeks after birth, the bacterial load in the lungs increased, and representation of the bacterial phyla shifts from a predominance of Gammaproteobacteria and Firmicutes towards Bacteroidetes. The changes in the microbiota were associated with decreased aeroallergen responsiveness and the emergence of a Helios(-) T-reg cell subset that required interaction with programmed death ligand 1 (PD-L1) for development. Absence of microbial colonization(10) or blockade of PD-L1 during the first 2 weeks postpartum maintained exaggerated responsiveness to allergens through to adulthood. Adoptive transfer of Treg cells from adult mice to neonates before aeroallergen exposure ameliorated disease. Thus, formation of the airway microbiota induces regulatory cells early in life, which, when dysregulated, can lead to sustained susceptibility to allergic airway inflammation in adulthood.. regulatory t-cells| immune-system| early-life| childhood asthma| colonization| farm| inflammation| pregnancy| bacterium| exposure.	JUN-2014	regulatory t-cells| immune-system| early-life| childhood asthma| colonization| farm| inflammation| pregnancy| bacterium| exposure	Gollwitzer, ES; Saglani, S; Trompette, A; Yadava, K; Sherburn, R; McCoy, KD; Nicod, LP; Lloyd, CM; Marsland, BJ	Lung microbiota promotes tolerance to allergens in neonates via PD-L1		NATURE MEDICINE		REGULATORY T-CELLS; IMMUNE-SYSTEM; EARLY-LIFE; CHILDHOOD ASTHMA; COLONIZATION; FARM; INFLAMMATION; PREGNANCY; BACTERIUM; EXPOSURE	Epidemiological data point toward a critical period in early life during which environmental cues can set an individual on a trajectory toward respiratory health or disease(1-8). The neonatal immune system matures during this period(9), although little is known about the signals that lead to its maturation. Here we report that the formation of the lung microbiota is a key parameter in this process. Immediately following birth, neonatal mice were prone to develop exaggerated airway eosinophilia, release type 2 helper T cell cytokines and exhibit airway hyper-responsiveness following exposure to house dust mite allergens, even though their lungs harbored high numbers of natural CD4(+)Foxp3(+)CD25(+)Helios(+) regulatory T (T-reg cells. During the first 2 weeks after birth, the bacterial load in the lungs increased, and representation of the bacterial phyla shifts from a predominance of Gammaproteobacteria and Firmicutes towards Bacteroidetes. The changes in the microbiota were associated with decreased aeroallergen responsiveness and the emergence of a Helios(-) T-reg cell subset that required interaction with programmed death ligand 1 (PD-L1) for development. Absence of microbial colonization(10) or blockade of PD-L1 during the first 2 weeks postpartum maintained exaggerated responsiveness to allergens through to adulthood. Adoptive transfer of Treg cells from adult mice to neonates before aeroallergen exposure ameliorated disease. Thus, formation of the airway microbiota induces regulatory cells early in life, which, when dysregulated, can lead to sustained susceptibility to allergic airway inflammation in adulthood.	30	97	2014	6	10.1038/nm.3568	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
IL-33 and ST2 in Atopic Dermatitis: Expression Profiles and Modulation by Triggering Factors. In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-alpha and IFN-gamma, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.. t-cells| mast-cells| human macrophages| family cytokine| murine model| flaky tail| filaggrin| disease| rna| sensitization.	MAY-2012	t-cells| mast-cells| human macrophages| family cytokine| murine model| flaky tail| filaggrin| disease| rna| sensitization	Savinko, T; Matikainen, S; Saarialho-Kere, U; Lehto, M; Wang, GY; Lehtimaki, S; Karisola, P; Reunala, T; Wolff, H; Lauerma, A; Alenius, H	IL-33 and ST2 in Atopic Dermatitis: Expression Profiles and Modulation by Triggering Factors		JOURNAL OF INVESTIGATIVE DERMATOLOGY		T-CELLS; MAST-CELLS; HUMAN MACROPHAGES; FAMILY CYTOKINE; MURINE MODEL; FLAKY TAIL; FILAGGRIN; DISEASE; RNA; SENSITIZATION	In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-alpha and IFN-gamma, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.	44	97	2012	9	10.1038/jid.2011.446	Dermatology
The Impact of Bisphenol A and Triclosan on Immune Parameters in the U.S. Population, NHANES 2003-2006. BACKGROUND: Exposure to environmental toxicants is associated with numerous disease outcomes, many of which involve underlying immune and inflammatory dysfunction. OBJECTIVES: To address the gap between environmental exposures and immune dysfunction, we investigated the association of two endocrine-disrupting compounds (EDCs) with markers of immune function. METHODS: Using data from the 2003-2006 National Health and Nutrition Examination Survey, we compared urinary bisphenol A (BPA) and triclosan levels with serum cytomegalovirus (CMV) antibody levels and diagnosis of allergies or hay fever in U. S. adults and children >= 6 years of age. We used multivariate ordinary least squares linear regression models to examine the association of BPA and triclosan with CMV antibody titers, and multivariate logistic regression models to investigate the association of these chemicals with allergy or hay fever diagnosis. Statistical models were stratified by age (< 18 years and >= 18 years). RESULTS: In analyses adjusted for age, sex, race, body mass index, creatinine levels, family income, and educational attainment, in the >= 18-year age group, higher urinary BPA levels were associated with higher CMV antibody titers (p < 0.001). In the < 18-year age group, lower levels of BPA were associated with higher CMV antibody titers (p < 0.05). However, triclosan, but not BPA, showed a positive association with allergy or hay fever diagnosis. In the < 18-year age group, higher levels of triclosan were associated with greater odds of having been diagnosed with allergies or hay fever (p < 0.01). CONCLUSIONS: EDCs such as BPA and triclosan may negatively affect human immune function as measured by CMV antibody levels and allergy or hay fever diagnosis, respectively, with differential consequences based on age. Additional studies should be done to investigate these findings.. allergies| bisphenol a| cytomegalovirus| endocrine-disrupting compounds| nhanes| triclosan|nutrition examination survey| human cytomegalovirus| endocrine disrupters| national-health| us population| antibodies| exposure| urinary| system| cells.	MAR-2011	allergies| bisphenol a| cytomegalovirus| endocrine-disrupting compounds| nhanes| triclosan|nutrition examination survey| human cytomegalovirus| endocrine disrupters| national-health| us population| antibodies| exposure| urinary| system| cells	Clayton, EMR; Todd, M; Dowd, JB; Aiello, AE	The Impact of Bisphenol A and Triclosan on Immune Parameters in the U.S. Population, NHANES 2003-2006		ENVIRONMENTAL HEALTH PERSPECTIVES	allergies; bisphenol A; cytomegalovirus; endocrine-disrupting compounds; NHANES; triclosan	NUTRITION EXAMINATION SURVEY; HUMAN CYTOMEGALOVIRUS; ENDOCRINE DISRUPTERS; NATIONAL-HEALTH; US POPULATION; ANTIBODIES; EXPOSURE; URINARY; SYSTEM; CELLS	BACKGROUND: Exposure to environmental toxicants is associated with numerous disease outcomes, many of which involve underlying immune and inflammatory dysfunction. OBJECTIVES: To address the gap between environmental exposures and immune dysfunction, we investigated the association of two endocrine-disrupting compounds (EDCs) with markers of immune function. METHODS: Using data from the 2003-2006 National Health and Nutrition Examination Survey, we compared urinary bisphenol A (BPA) and triclosan levels with serum cytomegalovirus (CMV) antibody levels and diagnosis of allergies or hay fever in U. S. adults and children >= 6 years of age. We used multivariate ordinary least squares linear regression models to examine the association of BPA and triclosan with CMV antibody titers, and multivariate logistic regression models to investigate the association of these chemicals with allergy or hay fever diagnosis. Statistical models were stratified by age (< 18 years and >= 18 years). RESULTS: In analyses adjusted for age, sex, race, body mass index, creatinine levels, family income, and educational attainment, in the >= 18-year age group, higher urinary BPA levels were associated with higher CMV antibody titers (p < 0.001). In the < 18-year age group, lower levels of BPA were associated with higher CMV antibody titers (p < 0.05). However, triclosan, but not BPA, showed a positive association with allergy or hay fever diagnosis. In the < 18-year age group, higher levels of triclosan were associated with greater odds of having been diagnosed with allergies or hay fever (p < 0.01). CONCLUSIONS: EDCs such as BPA and triclosan may negatively affect human immune function as measured by CMV antibody levels and allergy or hay fever diagnosis, respectively, with differential consequences based on age. Additional studies should be done to investigate these findings.	51	97	2011	7	10.1289/ehp.1002883	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Aspirin-Exacerbated Respiratory Disease: Evaluation and Management. The clinical syndrome of aspirin-exacerbated respiratory disease (AERD) is a condition where inhibition of cyclooxygenase-1 (COX-1) induces attacks of upper and lower airway reactions, including rhinorrhea and varying degrees of bronchospasm and laryngospasm. Although the reaction is not IgE-mediated, patients can also present with anaphylactic hypersensitivity reactions, including hypotension, after exposure to COX-1 inhibiting drugs. All patients with AERD have underlying nasal polyps and intractable sinus disease which may be difficult to treat with standard medical and surgical interventions. This review article focuses on the management of AERD patients with a particular emphasis on aspirin desensitization and continuous treatment with aspirin.. aspirin-exacerbated respiratory disease| aspirin desensitization| aspirin sensitivity| chronic sinusitis| asthma| nasal polyps| samter's triad|leukotriene-modifier drugs| long-term treatment| induced asthma| desensitization-treatment| sensitive asthmatics| intolerant asthma| controlled-trial| natural-history| lysine-aspirin| challenge.	JAN-2011	aspirin-exacerbated respiratory disease| aspirin desensitization| aspirin sensitivity| chronic sinusitis| asthma| nasal polyps| samter's triad|leukotriene-modifier drugs| long-term treatment| induced asthma| desensitization-treatment| sensitive asthmatics| intolerant asthma| controlled-trial| natural-history| lysine-aspirin| challenge	Lee, RU; Stevenson, DD	Aspirin-Exacerbated Respiratory Disease: Evaluation and Management		ALLERGY ASTHMA & IMMUNOLOGY RESEARCH	Aspirin-exacerbated respiratory disease; aspirin desensitization; aspirin sensitivity; chronic sinusitis; asthma; nasal polyps; Samter's triad	LEUKOTRIENE-MODIFIER DRUGS; LONG-TERM TREATMENT; INDUCED ASTHMA; DESENSITIZATION-TREATMENT; SENSITIVE ASTHMATICS; INTOLERANT ASTHMA; CONTROLLED-TRIAL; NATURAL-HISTORY; LYSINE-ASPIRIN; CHALLENGE	The clinical syndrome of aspirin-exacerbated respiratory disease (AERD) is a condition where inhibition of cyclooxygenase-1 (COX-1) induces attacks of upper and lower airway reactions, including rhinorrhea and varying degrees of bronchospasm and laryngospasm. Although the reaction is not IgE-mediated, patients can also present with anaphylactic hypersensitivity reactions, including hypotension, after exposure to COX-1 inhibiting drugs. All patients with AERD have underlying nasal polyps and intractable sinus disease which may be difficult to treat with standard medical and surgical interventions. This review article focuses on the management of AERD patients with a particular emphasis on aspirin desensitization and continuous treatment with aspirin.	46	97	2011	8	10.4168/aair.2011.3.1.3	Allergy; Immunology
Human health risks in megacities due to air pollution. This study evaluates the health risks in megacities in terms of mortality and morbidity due to air pollution. A new spreadsheet model, Risk of Mortality/Morbidity due to Air Pollution (Ri-MAP), is used to estimate the excess numbers of deaths and illnesses. By adopting the World Health Organization (WHO) guideline concentrations for the air pollutants SO(2), NO(2) and total suspended particles (TSP), concentration-response relationships and a population attributable-risk proportion concept are employed. Results suggest that some megacities like Los Angeles, New York, Osaka Kobe, Sao Paulo and Tokyo have very low excess cases in total mortality from these pollutants. In contrast, the approximate numbers of cases is highest in Karachi (15,000/yr) characterized by a very high concentration of total TSP (similar to 670 mu g m(-3)). Dhaka (7000/yr), Beijing (5500/yr), Karachi (5200/yr), Cairo (5000/yr) and Delhi (3500/yr) rank highest with cardiovascular mortality. The morbidity (hospital admissions) due to Chronic Obstructive Pulmonary Disease (COPD) follows the tendency of cardiovascular mortality. Dhaka and Karachi lead the rankings, having about 2100/yr excess cases, while Osaka-Kobe (similar to 20/yr) and Sao Paulo (similar to 50/yr) are at the low end of all megacities considered. Since air pollution is increasing in many megacities, and our database of measured pollutants is limited to the period up to 2000 and does not include all relevant components (e.g. O(3)), these numbers should be interpreted as lower limits. South Asian megacities most urgently need improvement of air quality to prevent excess mortality and morbidity due to exceptionally high levels of air pollution. The risk estimates obtained from Ri-MAP present a realistic baseline evaluation for the consequences of ambient air pollution in comparison to simple air quality indices, and can be expanded and improved in parallel with the development of air pollution monitoring networks. (C) 2010 Elsevier Ltd. All rights reserved.. criteria pollutants| mortality| morbidity| relative risk| cardiovascular| respiratory| hospital admissions|united-states| hospital admissions| aphea project| pollutants| mortality| exposure| emissions| cities| asthma.	NOV-2010	criteria pollutants| mortality| morbidity| relative risk| cardiovascular| respiratory| hospital admissions|united-states| hospital admissions| aphea project| pollutants| mortality| exposure| emissions| cities| asthma	Gurjar, BR; Jain, A; Sharma, A; Agarwal, A; Gupta, P; Nagpure, AS; Lelieveld, J	Human health risks in megacities due to air pollution		ATMOSPHERIC ENVIRONMENT	Criteria pollutants; Mortality; Morbidity; Relative risk; Cardiovascular; Respiratory; Hospital admissions	UNITED-STATES; HOSPITAL ADMISSIONS; APHEA PROJECT; POLLUTANTS; MORTALITY; EXPOSURE; EMISSIONS; CITIES; ASTHMA	This study evaluates the health risks in megacities in terms of mortality and morbidity due to air pollution. A new spreadsheet model, Risk of Mortality/Morbidity due to Air Pollution (Ri-MAP), is used to estimate the excess numbers of deaths and illnesses. By adopting the World Health Organization (WHO) guideline concentrations for the air pollutants SO(2), NO(2) and total suspended particles (TSP), concentration-response relationships and a population attributable-risk proportion concept are employed. Results suggest that some megacities like Los Angeles, New York, Osaka Kobe, Sao Paulo and Tokyo have very low excess cases in total mortality from these pollutants. In contrast, the approximate numbers of cases is highest in Karachi (15,000/yr) characterized by a very high concentration of total TSP (similar to 670 mu g m(-3)). Dhaka (7000/yr), Beijing (5500/yr), Karachi (5200/yr), Cairo (5000/yr) and Delhi (3500/yr) rank highest with cardiovascular mortality. The morbidity (hospital admissions) due to Chronic Obstructive Pulmonary Disease (COPD) follows the tendency of cardiovascular mortality. Dhaka and Karachi lead the rankings, having about 2100/yr excess cases, while Osaka-Kobe (similar to 20/yr) and Sao Paulo (similar to 50/yr) are at the low end of all megacities considered. Since air pollution is increasing in many megacities, and our database of measured pollutants is limited to the period up to 2000 and does not include all relevant components (e.g. O(3)), these numbers should be interpreted as lower limits. South Asian megacities most urgently need improvement of air quality to prevent excess mortality and morbidity due to exceptionally high levels of air pollution. The risk estimates obtained from Ri-MAP present a realistic baseline evaluation for the consequences of ambient air pollution in comparison to simple air quality indices, and can be expanded and improved in parallel with the development of air pollution monitoring networks. (C) 2010 Elsevier Ltd. All rights reserved.	33	97	2010	8	10.1016/j.atmosenv.2010.08.011	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Anaphylaxis: Recent advances in assessment and treatment. The incidence rate of anaphylaxis is increasing, particularly during the first 2 decades of life. Common triggers include foods, medications, and insect stings. Clinical diagnosis is based on a meticulous history of an exposure or event preceding characteristic symptoms and signs, sometimes but not always supported by a laboratory test such as an elevated serum total tryptase level. Physician-initiated investigation of patients with anaphylaxis whose symptoms and signs are atypical sometimes leads to important insights into previously unrecognized triggers and mechanisms. In idiopathic anaphylaxis, in which no trigger can be confirmed by means of skin testing or measurement of specific IgE, the possibility of mastocytosis or a clonal mast cell disorder must be considered in addition to the possibility of a previously unrecognized trigger. Long-term risk reduction in patients with anaphylaxis focuses on optimal management of relevant comorbidities such as asthma and other respiratory diseases, cardiovascular disease, and mastocytosis or a clonal mast cell disorder; avoidance of the relevant confirmed allergen trigger; and relevant immunomodulation such as medication desensitization, venom immunotherapy, and possibly in the future, immunotherapy with food. Emergency preparedness for recurrence of anaphylaxis in community settings includes having epinephrine (adrenaline) autoinjectors available, knowing when and how to use them, and having a written, personalized anaphylaxis emergency action plan and up-to-date medical identification. Randomized controlled trials of the pharmacologic interventions used in an acute anaphylaxis episode are needed. (J Allergy Clin Immunol 2009;124:625-36.). anaphylaxis| systemic allergic reaction| food allergy| medication allergy| insect venom allergy| epinephrine| adrenaline|indolent systemic mastocytosis| epinephrine auto-injectors| oral tolerance induction| long-term management| insect sting allergy| of-the-literature| food allergy| hypersensitivity reactions| emergency-department| venom immunotherapy.	OCT-2009	anaphylaxis| systemic allergic reaction| food allergy| medication allergy| insect venom allergy| epinephrine| adrenaline|indolent systemic mastocytosis| epinephrine auto-injectors| oral tolerance induction| long-term management| insect sting allergy| of-the-literature| food allergy| hypersensitivity reactions| emergency-department| venom immunotherapy	Simons, FER	Anaphylaxis: Recent advances in assessment and treatment		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Anaphylaxis; systemic allergic reaction; food allergy; medication allergy; insect venom allergy; epinephrine; adrenaline	INDOLENT SYSTEMIC MASTOCYTOSIS; EPINEPHRINE AUTO-INJECTORS; ORAL TOLERANCE INDUCTION; LONG-TERM MANAGEMENT; INSECT STING ALLERGY; OF-THE-LITERATURE; FOOD ALLERGY; HYPERSENSITIVITY REACTIONS; EMERGENCY-DEPARTMENT; VENOM IMMUNOTHERAPY	The incidence rate of anaphylaxis is increasing, particularly during the first 2 decades of life. Common triggers include foods, medications, and insect stings. Clinical diagnosis is based on a meticulous history of an exposure or event preceding characteristic symptoms and signs, sometimes but not always supported by a laboratory test such as an elevated serum total tryptase level. Physician-initiated investigation of patients with anaphylaxis whose symptoms and signs are atypical sometimes leads to important insights into previously unrecognized triggers and mechanisms. In idiopathic anaphylaxis, in which no trigger can be confirmed by means of skin testing or measurement of specific IgE, the possibility of mastocytosis or a clonal mast cell disorder must be considered in addition to the possibility of a previously unrecognized trigger. Long-term risk reduction in patients with anaphylaxis focuses on optimal management of relevant comorbidities such as asthma and other respiratory diseases, cardiovascular disease, and mastocytosis or a clonal mast cell disorder; avoidance of the relevant confirmed allergen trigger; and relevant immunomodulation such as medication desensitization, venom immunotherapy, and possibly in the future, immunotherapy with food. Emergency preparedness for recurrence of anaphylaxis in community settings includes having epinephrine (adrenaline) autoinjectors available, knowing when and how to use them, and having a written, personalized anaphylaxis emergency action plan and up-to-date medical identification. Randomized controlled trials of the pharmacologic interventions used in an acute anaphylaxis episode are needed. (J Allergy Clin Immunol 2009;124:625-36.)	99	97	2009	12	10.1016/j.jaci.2009.08.025	Allergy; Immunology
Air pollution and emergency department visits for cardiac and respiratory conditions: a multi-city time-series analysis. Background: Relatively few studies have been conducted of the association between air pollution and emergency department (ED) visits, and most of these have been based on a small number of visits, for a limited number of health conditions and pollutants, and only daily measures of exposure and response. Methods: A time-series analysis was conducted on nearly 400,000 ED visits to 14 hospitals in seven Canadian cities during the 1990s and early 2000s. Associations were examined between carbon monoxide (CO), nitrogen dioxide (NO(2)), ozone (O(3)), sulfur dioxide (SO(2)), and particulate matter (PM(10) and PM(2.5)), and visits for angina/myocardial infarction, heart failure, dysrhythmia/conduction disturbance, asthma, chronic obstructive pulmonary disease (COPD), and respiratory infections. Daily and 3-hourly visit counts were modeled as quasi-Poisson and analyses controlled for effects of temporal cycles, weather, day of week and holidays. Results: 24-hour average concentrations of CO and NO(2) lag 0 days exhibited the most consistent associations with cardiac conditions (2.1% (95% CI, 0.0-4.2%) and 2.6% (95% CI, 0.2-5.0%) increase in visits for myocardial infarction/angina per 0.7 ppm CO and 18.4 ppb NO(2) respectively; 3.8% (95% CI, 0.7-6.9%) and 4.7% (95% CI, 1.2-8.4%) increase in visits for heart failure). Ozone (lag 2 days) was most consistently associated with respiratory visits (3.2% (95% CI, 0.3-6.2%), and 3.7% (95% CI,-0.5-7.9%) increases in asthma and COPD visits respectively per 18.4 ppb). Associations tended to be of greater magnitude during the warm season (April-September). In particular, the associations of PM(10) and PM(2.5) with asthma visits were respectively nearly three-and over fourfold larger vs. all year analyses (14.4% increase in visits, 95% CI, 0.2-30.7, per 20.6 mu g/m(3) PM(10) and 7.6% increase in visits, 95% CI, 5.1-10.1, per 8.2 mu g/m(3) PM(2.5)). No consistent associations were observed between three hour average pollutant concentrations and same-day three hour averages of ED visits. Conclusion: In this large multicenter analysis, daily average concentrations of CO and NO(2) exhibited the most consistent associations with ED visits for cardiac conditions, while ozone exhibited the most consistent associations with visits for respiratory conditions. PM(10) and PM(2.5) were strongly associated with asthma visits during the warm season.. heart-rate-variability| room visits| hospital admissions| asthma emergency| particulate matter| pulmonary-disease| childhood asthma| daily mortality| saint-john| association.	JUN 10-2009	heart-rate-variability| room visits| hospital admissions| asthma emergency| particulate matter| pulmonary-disease| childhood asthma| daily mortality| saint-john| association	Stieb, DM; Szyszkowicz, M; Rowe, BH; Leech, JA	Air pollution and emergency department visits for cardiac and respiratory conditions: a multi-city time-series analysis		ENVIRONMENTAL HEALTH		HEART-RATE-VARIABILITY; ROOM VISITS; HOSPITAL ADMISSIONS; ASTHMA EMERGENCY; PARTICULATE MATTER; PULMONARY-DISEASE; CHILDHOOD ASTHMA; DAILY MORTALITY; SAINT-JOHN; ASSOCIATION	Background: Relatively few studies have been conducted of the association between air pollution and emergency department (ED) visits, and most of these have been based on a small number of visits, for a limited number of health conditions and pollutants, and only daily measures of exposure and response. Methods: A time-series analysis was conducted on nearly 400,000 ED visits to 14 hospitals in seven Canadian cities during the 1990s and early 2000s. Associations were examined between carbon monoxide (CO), nitrogen dioxide (NO(2)), ozone (O(3)), sulfur dioxide (SO(2)), and particulate matter (PM(10) and PM(2.5)), and visits for angina/myocardial infarction, heart failure, dysrhythmia/conduction disturbance, asthma, chronic obstructive pulmonary disease (COPD), and respiratory infections. Daily and 3-hourly visit counts were modeled as quasi-Poisson and analyses controlled for effects of temporal cycles, weather, day of week and holidays. Results: 24-hour average concentrations of CO and NO(2) lag 0 days exhibited the most consistent associations with cardiac conditions (2.1% (95% CI, 0.0-4.2%) and 2.6% (95% CI, 0.2-5.0%) increase in visits for myocardial infarction/angina per 0.7 ppm CO and 18.4 ppb NO(2) respectively; 3.8% (95% CI, 0.7-6.9%) and 4.7% (95% CI, 1.2-8.4%) increase in visits for heart failure). Ozone (lag 2 days) was most consistently associated with respiratory visits (3.2% (95% CI, 0.3-6.2%), and 3.7% (95% CI,-0.5-7.9%) increases in asthma and COPD visits respectively per 18.4 ppb). Associations tended to be of greater magnitude during the warm season (April-September). In particular, the associations of PM(10) and PM(2.5) with asthma visits were respectively nearly three-and over fourfold larger vs. all year analyses (14.4% increase in visits, 95% CI, 0.2-30.7, per 20.6 mu g/m(3) PM(10) and 7.6% increase in visits, 95% CI, 5.1-10.1, per 8.2 mu g/m(3) PM(2.5)). No consistent associations were observed between three hour average pollutant concentrations and same-day three hour averages of ED visits. Conclusion: In this large multicenter analysis, daily average concentrations of CO and NO(2) exhibited the most consistent associations with ED visits for cardiac conditions, while ozone exhibited the most consistent associations with visits for respiratory conditions. PM(10) and PM(2.5) were strongly associated with asthma visits during the warm season.	36	97	2009	13	10.1186/1476-069X-8-25	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Ambient air pollution and asthma exacerbations in children: An eight-city analysis. The authors investigated the relation between ambient concentrations of five of the Environmental Protection Agency's criteria pollutants and asthma exacerbations (daily symptoms and use of rescue inhalers) among 990 children in eight North American cities during the 22-month prerandomization phase (November 1993-September 1995) of the Childhood Asthma Management Program. Short-term effects of carbon monoxide, nitrogen dioxide, particulate matter less than 10 mu m in aerodynamic diameter (PM10), sulfur dioxide, and warm-season ozone were examined in both one-pollutant and two-pollutant models, using lags of up to 2 days. Lags in carbon monoxide and nitrogen dioxide were positively associated with both measures of asthma exacerbation, and the 3-day moving sum of sulfur dioxide levels was marginally related to asthma symptoms. PM10 and ozone were unrelated to exacerbations. The strongest effects tended to be seen with 2-day lags, where a 1-parts-per-million change in carbon monoxide and a 20-parts-per-billion change in nitrogen dioxide were associated with symptom odds ratios of 1.08 (95% confidence interval (CI): 1.02, 1.15) and 1.09 (95% CI: 1.03, 1.15), respectively, and with rate ratios for rescue inhaler use of 1.06 (95% CI: 1.01, 1.10) and 1.05 (95% CI: 1.01, 1.09), respectively. The authors believe that the observed carbon monoxide and nitrogen dioxide associations can probably be attributed to mobile-source emissions, though more research is required.. air pollution| asthma| carbon monoxide| nitrogen dioxide| ozone| pediatrics| sulfur dioxide|longitudinal data-analysis| african-american children| particulate matter| respiratory health| inhaled allergen| symptom severity| nitrogen-dioxide| ozone exposure| medication use| mexico-city.	SEP 15-2006	air pollution| asthma| carbon monoxide| nitrogen dioxide| ozone| pediatrics| sulfur dioxide|longitudinal data-analysis| african-american children| particulate matter| respiratory health| inhaled allergen| symptom severity| nitrogen-dioxide| ozone exposure| medication use| mexico-city	Schildcrout, JS; Sheppard, L; Lumley, T; Slaughter, JC; Koenig, JQ; Shapiro, GG	Ambient air pollution and asthma exacerbations in children: An eight-city analysis		AMERICAN JOURNAL OF EPIDEMIOLOGY	air pollution; asthma; carbon monoxide; nitrogen dioxide; ozone; pediatrics; sulfur dioxide	LONGITUDINAL DATA-ANALYSIS; AFRICAN-AMERICAN CHILDREN; PARTICULATE MATTER; RESPIRATORY HEALTH; INHALED ALLERGEN; SYMPTOM SEVERITY; NITROGEN-DIOXIDE; OZONE EXPOSURE; MEDICATION USE; MEXICO-CITY	The authors investigated the relation between ambient concentrations of five of the Environmental Protection Agency's criteria pollutants and asthma exacerbations (daily symptoms and use of rescue inhalers) among 990 children in eight North American cities during the 22-month prerandomization phase (November 1993-September 1995) of the Childhood Asthma Management Program. Short-term effects of carbon monoxide, nitrogen dioxide, particulate matter less than 10 mu m in aerodynamic diameter (PM10), sulfur dioxide, and warm-season ozone were examined in both one-pollutant and two-pollutant models, using lags of up to 2 days. Lags in carbon monoxide and nitrogen dioxide were positively associated with both measures of asthma exacerbation, and the 3-day moving sum of sulfur dioxide levels was marginally related to asthma symptoms. PM10 and ozone were unrelated to exacerbations. The strongest effects tended to be seen with 2-day lags, where a 1-parts-per-million change in carbon monoxide and a 20-parts-per-billion change in nitrogen dioxide were associated with symptom odds ratios of 1.08 (95% confidence interval (CI): 1.02, 1.15) and 1.09 (95% CI: 1.03, 1.15), respectively, and with rate ratios for rescue inhaler use of 1.06 (95% CI: 1.01, 1.10) and 1.05 (95% CI: 1.01, 1.09), respectively. The authors believe that the observed carbon monoxide and nitrogen dioxide associations can probably be attributed to mobile-source emissions, though more research is required.	41	97	2006	13	10.1093/aje/kwj225	Public, Environmental & Occupational Health
Distribution and determinants of house dust mite allergens in Europe: the European Community Respiratory Health Survey II. Background: Several studies in European homes have described allergen levels from the house dust mite species Dermatophagoides pteronyssinus and to a lesser extent Dermatophagoides farinae, but geographic comparisons of exposure levels and risk factors have been hampered by a lack of standardized methods. Objective: To study the distribution and determinants of the major house dust mite allergens Der p 1 and Der f 1 in 10 European countries using a common protocol. Methods: During home visits with 3580 participants of the European Community Respiratory Health Survey II from 22 study centers, mattress dust was sampled and analyzed for Der p 1, Der f 1, and Der 2 allergen. Information on housing characteristics was obtained by both observations and interview. Results: Der 1 and Der 2 allergens were detectable (>= 0.1 mu g/g) in 68% and 53% of the samples, respectively. Large differences in allergen levels between study centers were observed, and geographic patterns for Der p 1 and Der f 1 were different. Low winter temperatures reduced Der p 1 rather than Der f 1. Important risk factors for high allergen levels included an older mattress, a lower floor level of the bedroom, limited ventilation of the bedroom, and dampness for Der p 1 but not for Der f 1. Conclusion: There are large qualitative and quantitative differences of house dust mite allergen levels in Europe, which can partly be explained by geographic and housing characteristics. Clinical implications: Mite allergen exposure may be reduced by replacing the mattress regularly and increasing ventilation of the bedroom, particularly in winter.. house dust mites| allergens| housing| risk factors| geographic| ecrhs|asthma| prevalence| der-p-1| homes| mattresses| symptoms| humidity| exposure.	SEP-2006	house dust mites| allergens| housing| risk factors| geographic| ecrhs|asthma| prevalence| der-p-1| homes| mattresses| symptoms| humidity| exposure	Zock, JP; Heinrich, J; Jarvis, D; Verlato, G; Norback, D; Plana, E; Sunyer, J; Chinn, S; Olivieri, M; Soon, A; Villani, S; Ponzio, M; Dahlman-Hoglund, A; Svanes, C; Luczynska, C	Distribution and determinants of house dust mite allergens in Europe: the European Community Respiratory Health Survey II		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	house dust mites; allergens; housing; risk factors; geographic; ECRHS	ASTHMA; PREVALENCE; DER-P-1; HOMES; MATTRESSES; SYMPTOMS; HUMIDITY; EXPOSURE	Background: Several studies in European homes have described allergen levels from the house dust mite species Dermatophagoides pteronyssinus and to a lesser extent Dermatophagoides farinae, but geographic comparisons of exposure levels and risk factors have been hampered by a lack of standardized methods. Objective: To study the distribution and determinants of the major house dust mite allergens Der p 1 and Der f 1 in 10 European countries using a common protocol. Methods: During home visits with 3580 participants of the European Community Respiratory Health Survey II from 22 study centers, mattress dust was sampled and analyzed for Der p 1, Der f 1, and Der 2 allergen. Information on housing characteristics was obtained by both observations and interview. Results: Der 1 and Der 2 allergens were detectable (>= 0.1 mu g/g) in 68% and 53% of the samples, respectively. Large differences in allergen levels between study centers were observed, and geographic patterns for Der p 1 and Der f 1 were different. Low winter temperatures reduced Der p 1 rather than Der f 1. Important risk factors for high allergen levels included an older mattress, a lower floor level of the bedroom, limited ventilation of the bedroom, and dampness for Der p 1 but not for Der f 1. Conclusion: There are large qualitative and quantitative differences of house dust mite allergen levels in Europe, which can partly be explained by geographic and housing characteristics. Clinical implications: Mite allergen exposure may be reduced by replacing the mattress regularly and increasing ventilation of the bedroom, particularly in winter.	29	97	2006	9	10.1016/j.jaci.2006.04.060	Allergy; Immunology
Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. In a mouse experimental asthma model, the administration of bacterial lipopolysaccharide (LIPS), particularly at low doses, enhances the levels of ovalbumin (OVA)-induced eosinophilic airway inflammation. In an effort to clarify the cellular and molecular basis for the LPS effect, we demonstrate that the OVA-induced eosinophilic inflammation in the lung is dramatically increased by the administration of LPS in wild-type mice, whereas such increase was not observed in mast-cell-deficient mice or Toll-like receptor (TLR)4-deficient mice. Adoptive transfer of bone-marrow-derived mast cells (BMMCs) from wild-type, but not from TLR4-deficient, mice restored the increased eosinophilic inflammation in mast-cell-deficient mice. Wild-type BMMCs pretreated with LPS in vitro also reconstituted the eosinophilic inflammation. Moreover, in vitro analysis revealed that the treatment of BMMCs with LPS resulted in NF-kappa B activation, sustained up-regulation of GATA1 and -2 expression, and increased the capability to produce IL-5 and -13. Dramatic increases in the expression of IL-5 and -13 and Eotaxin 2 were detected in LIPS-treated BMMCs after costimulation with LIPS and IgE/Ag. Overexpression of GATA1, but not GATA2, in MC9 mast cells resulted in increased transcriptional activity of IL-4, -5, and -13. Furthermore, the levels of transcription of Th2 cytokines in BMMCs were decreased by the introduction of small interfering RNA for GATA1. Thus, mast cells appear to control allergic airway inflammation after their activation and modulation through TLR4-mediated induction of GATA1 and subsequent increase in Th2 cytokine production.. cytokine| gata1| mast cell| lipopolysaccharide| bone-marrow-derived mast cells|endotoxin exposure| gene locus| histone hyperacetylation| innate immunity| cutting edge| tnf-alpha| t-cells| asthma| differentiation| lipopolysaccharide.	FEB 14-2006	cytokine| gata1| mast cell| lipopolysaccharide| bone-marrow-derived mast cells|endotoxin exposure| gene locus| histone hyperacetylation| innate immunity| cutting edge| tnf-alpha| t-cells| asthma| differentiation| lipopolysaccharide	Nigo, YI; Yamashita, M; Hirahara, K; Shinnakasu, R; Inami, M; Kimura, M; Hasegawa, A; Kohno, Y; Nakayama, T	Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	cytokine; GATA1; mast cell; lipopolysaccharide; bone-marrow-derived mast cells	ENDOTOXIN EXPOSURE; GENE LOCUS; HISTONE HYPERACETYLATION; INNATE IMMUNITY; CUTTING EDGE; TNF-ALPHA; T-CELLS; ASTHMA; DIFFERENTIATION; LIPOPOLYSACCHARIDE	In a mouse experimental asthma model, the administration of bacterial lipopolysaccharide (LIPS), particularly at low doses, enhances the levels of ovalbumin (OVA)-induced eosinophilic airway inflammation. In an effort to clarify the cellular and molecular basis for the LPS effect, we demonstrate that the OVA-induced eosinophilic inflammation in the lung is dramatically increased by the administration of LPS in wild-type mice, whereas such increase was not observed in mast-cell-deficient mice or Toll-like receptor (TLR)4-deficient mice. Adoptive transfer of bone-marrow-derived mast cells (BMMCs) from wild-type, but not from TLR4-deficient, mice restored the increased eosinophilic inflammation in mast-cell-deficient mice. Wild-type BMMCs pretreated with LPS in vitro also reconstituted the eosinophilic inflammation. Moreover, in vitro analysis revealed that the treatment of BMMCs with LPS resulted in NF-kappa B activation, sustained up-regulation of GATA1 and -2 expression, and increased the capability to produce IL-5 and -13. Dramatic increases in the expression of IL-5 and -13 and Eotaxin 2 were detected in LIPS-treated BMMCs after costimulation with LIPS and IgE/Ag. Overexpression of GATA1, but not GATA2, in MC9 mast cells resulted in increased transcriptional activity of IL-4, -5, and -13. Furthermore, the levels of transcription of Th2 cytokines in BMMCs were decreased by the introduction of small interfering RNA for GATA1. Thus, mast cells appear to control allergic airway inflammation after their activation and modulation through TLR4-mediated induction of GATA1 and subsequent increase in Th2 cytokine production.	52	97	2006	6	10.1073/pnas.0510685103	Science & Technology - Other Topics
IgE, mast cells, basophils, and eosinophils. IgE, mast cells, basophils, and eosinophils constitute essential elements in allergic inflammation. Allergen-specific IgE, synthesized in response to allergens in the environment, becomes fixed to Fc epsilon RI on the membranes of mast cells and basophils. Aggregation of receptor-bound IgE molecules on re-exposure to specific allergen results in the production of mediators that produce the allergic response. Principal among the cells drawn to sites of mediator release is the eosinophil.. ige| ige receptor| mast cell| basophil| eosinophil|fc-epsilon-ri| host-defense| hypereosinophilic syndrome| asthma| receptor| activation| expression| deficient| secretion| roles.	FEB-2006	ige| ige receptor| mast cell| basophil| eosinophil|fc-epsilon-ri| host-defense| hypereosinophilic syndrome| asthma| receptor| activation| expression| deficient| secretion| roles	Prussin, C; Metcalfe, DD	IgE, mast cells, basophils, and eosinophils		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	IgE; IgE receptor; mast cell; basophil; eosinophil	FC-EPSILON-RI; HOST-DEFENSE; HYPEREOSINOPHILIC SYNDROME; ASTHMA; RECEPTOR; ACTIVATION; EXPRESSION; DEFICIENT; SECRETION; ROLES	IgE, mast cells, basophils, and eosinophils constitute essential elements in allergic inflammation. Allergen-specific IgE, synthesized in response to allergens in the environment, becomes fixed to Fc epsilon RI on the membranes of mast cells and basophils. Aggregation of receptor-bound IgE molecules on re-exposure to specific allergen results in the production of mediators that produce the allergic response. Principal among the cells drawn to sites of mediator release is the eosinophil.	34	97	2006	7	10.1016/j.jaci.2005.11.016	Allergy; Immunology
Bacterial and fungal agents in house dust and wheeze in children: the PARSIFAL study. Background Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. This might be related to increased inhalatory exposure to microbial agents. Objective To assess the association between microbial agents in house dust and atopic wheeze in farm children, Steiner school children and reference children. Methods Levels of bacterial endotoxin, fungal beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in mattress and living room floor dust were measured in a population of 270 atopic (=Phadiatop-positive) children with self-reported wheezing, including 168 current atopic wheezers, and 441 non-atopic, non-symptomatic controls. These children were selected from a cross-sectional study in five European countries. Results In the study population as a whole, average levels of mattress dust endotoxin, EPS and glucans were slightly (1.1-1.2-fold; P < 0.10) higher in control children than in atopic wheezers. Atopic wheeze was related to mattress levels of endotoxin, EPS and glucans in farm and farm-reference children. However, when adjusting for group (farm vs. farm-reference children), the associations became non-significant whereas the group effect remained. No associations between atopic wheeze and microbial agents were observed in Steiner and Steiner-reference children. For current atopic wheeze, the farm effect became non-significant after adjustment for microbial agent levels. Conclusion Not only bacterial endotoxin but also mould components might offer some protection against atopic wheeze in children. However, the protective effect of being raised on a farm was largely unexplained by the mattress microbial agent levels measured in this study.. asthma| beta(1,3)-glucans| endotoxin| farm| fungal extracellular polysaccharides|extracellular polysaccharides| allergic sensitization| culturable fungi| hay-fever| asthma| farm| endotoxin| exposure| atopy| (1->3)-beta-d-glucan.	OCT-2005	asthma| beta(1,3)-glucans| endotoxin| farm| fungal extracellular polysaccharides|extracellular polysaccharides| allergic sensitization| culturable fungi| hay-fever| asthma| farm| endotoxin| exposure| atopy| (1->3)-beta-d-glucan	Schram-Bijkerk, D; Doekes, G; Douwes, J; Boeve, M; Riedler, J; Ublagger, E; Mutius, E; Benz, MR; Pershagen, G; Hage, M; Scheynius, A; Braun-Fahrlander, C; Waser, M; Brunekreef, B	Bacterial and fungal agents in house dust and wheeze in children: the PARSIFAL study		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; beta(1,3)-glucans; endotoxin; farm; fungal extracellular polysaccharides	EXTRACELLULAR POLYSACCHARIDES; ALLERGIC SENSITIZATION; CULTURABLE FUNGI; HAY-FEVER; ASTHMA; FARM; ENDOTOXIN; EXPOSURE; ATOPY; (1->3)-BETA-D-GLUCAN	Background Growing up on a farm and an anthroposophic lifestyle are associated with a lower prevalence of allergic diseases in childhood. This might be related to increased inhalatory exposure to microbial agents. Objective To assess the association between microbial agents in house dust and atopic wheeze in farm children, Steiner school children and reference children. Methods Levels of bacterial endotoxin, fungal beta(1,3)-glucans and fungal extracellular polysaccharides (EPS) in mattress and living room floor dust were measured in a population of 270 atopic (=Phadiatop-positive) children with self-reported wheezing, including 168 current atopic wheezers, and 441 non-atopic, non-symptomatic controls. These children were selected from a cross-sectional study in five European countries. Results In the study population as a whole, average levels of mattress dust endotoxin, EPS and glucans were slightly (1.1-1.2-fold; P < 0.10) higher in control children than in atopic wheezers. Atopic wheeze was related to mattress levels of endotoxin, EPS and glucans in farm and farm-reference children. However, when adjusting for group (farm vs. farm-reference children), the associations became non-significant whereas the group effect remained. No associations between atopic wheeze and microbial agents were observed in Steiner and Steiner-reference children. For current atopic wheeze, the farm effect became non-significant after adjustment for microbial agent levels. Conclusion Not only bacterial endotoxin but also mould components might offer some protection against atopic wheeze in children. However, the protective effect of being raised on a farm was largely unexplained by the mattress microbial agent levels measured in this study.	31	97	2005	7	10.1111/j.1365-2222.2005.02339.x	Allergy; Immunology
Prevalence of snoring and symptoms of sleep-disordered breathing in primary school children in Istanbul. Study objectives: Snoring during sleep is an important manifestation of obstructive sleep apnea syndrome (OSAS). Although clinical history is not sufficiently sensitive and specific to distinguish primary snoring from OSAS, snoring is indicative of upper airway obstruction and may be associated with the presence of diurnal symptoms. Our study aims were to determine the prevalence of snoring in primary school children in Istanbul, and to evaluate the diurnal symptoms and conditions that may be associated with sleep problems. Design, setting, and subjects: A parental questionnaire was used to assess the sleep and wake behavioral patterns in children. Eight representative schools in each of 9 school districts randomly selected from the 32 school districts in Istanbul were visited. Results: The response rate was 78.1%; 2,147 of 2,746 questionnaires were fully completed, returned, and analyzed. The prevalence of habitual snoring was 7.0%. Habitual snorers had significantly more nighttime symptoms, such as observed apneas (odds ratio [OR], 16.9; 95% confidence interval [CI], 10.0 to 28.8; p < 0.0001), difficulty breathing (OR, 17.8; CI, 10.9 to 29.2; p < 0.0001), restless sleep, parasomnias, and nocturnal enuresis, compared to occasional and nonsnorers. There were also increased prevalence of daytime symptoms, such as falling asleep while watching television (OR, 1.8; CI, 0.9 to 3.7; p = 0.01) and in public places (OR, 2.1; CI, 1.2 to 3.8; p = 0.03), and hyperactivity (OR, 2.7; CI, 1.8 to 3.9; p < 0.0001). Exposure to cigarette smoke and the presence of asthma and hay fever increased the likelihood of habitual snoring. Children with a higher risk for OSAS (habitual snoring, apnea, and difficulty breathing during sleep) were also compared to nonsnorers. Although nighttime symptoms were more likely in the high-risk group, the risk of daytime symptoms increased as well. Conclusions: Habitual snoring is a significant problem for children and may be associated with diurnal symptoms. Exposure to cigarette smoke at home and the presence of asthma and hay fever increase the likelihood of habitual snoring.. children| hyperactivity| passive smoke exposure| prevalence| snoring|apnea syndrome| nocturnal hypoxemia| preschool-children| performance| disturbance| association| behavior| smoking.	JUL-2004	children| hyperactivity| passive smoke exposure| prevalence| snoring|apnea syndrome| nocturnal hypoxemia| preschool-children| performance| disturbance| association| behavior| smoking	Ersu, R; Arman, AR; Save, D; Karadag, B; Karakoc, F; Berkem, M; Dagli, E	Prevalence of snoring and symptoms of sleep-disordered breathing in primary school children in Istanbul		CHEST	children; hyperactivity; passive smoke exposure; prevalence; snoring	APNEA SYNDROME; NOCTURNAL HYPOXEMIA; PRESCHOOL-CHILDREN; PERFORMANCE; DISTURBANCE; ASSOCIATION; BEHAVIOR; SMOKING	Study objectives: Snoring during sleep is an important manifestation of obstructive sleep apnea syndrome (OSAS). Although clinical history is not sufficiently sensitive and specific to distinguish primary snoring from OSAS, snoring is indicative of upper airway obstruction and may be associated with the presence of diurnal symptoms. Our study aims were to determine the prevalence of snoring in primary school children in Istanbul, and to evaluate the diurnal symptoms and conditions that may be associated with sleep problems. Design, setting, and subjects: A parental questionnaire was used to assess the sleep and wake behavioral patterns in children. Eight representative schools in each of 9 school districts randomly selected from the 32 school districts in Istanbul were visited. Results: The response rate was 78.1%; 2,147 of 2,746 questionnaires were fully completed, returned, and analyzed. The prevalence of habitual snoring was 7.0%. Habitual snorers had significantly more nighttime symptoms, such as observed apneas (odds ratio [OR], 16.9; 95% confidence interval [CI], 10.0 to 28.8; p < 0.0001), difficulty breathing (OR, 17.8; CI, 10.9 to 29.2; p < 0.0001), restless sleep, parasomnias, and nocturnal enuresis, compared to occasional and nonsnorers. There were also increased prevalence of daytime symptoms, such as falling asleep while watching television (OR, 1.8; CI, 0.9 to 3.7; p = 0.01) and in public places (OR, 2.1; CI, 1.2 to 3.8; p = 0.03), and hyperactivity (OR, 2.7; CI, 1.8 to 3.9; p < 0.0001). Exposure to cigarette smoke and the presence of asthma and hay fever increased the likelihood of habitual snoring. Children with a higher risk for OSAS (habitual snoring, apnea, and difficulty breathing during sleep) were also compared to nonsnorers. Although nighttime symptoms were more likely in the high-risk group, the risk of daytime symptoms increased as well. Conclusions: Habitual snoring is a significant problem for children and may be associated with diurnal symptoms. Exposure to cigarette smoke at home and the presence of asthma and hay fever increase the likelihood of habitual snoring.	28	97	2004	6	10.1378/chest.126.1.19	General & Internal Medicine; Respiratory System
The burden of disease from indoor air pollution in developing countries: comparison of estimates. Four different methods have been applied to estimate the burden of disease due to indoor air pollution from household solid fuel use in developing countries (LDCs). The largest number of estimates involves applying exposure-response information from urban ambient air pollution studies to estimate indoor exposure concentrations of particulate air pollution. Another approach is to construct child survival curves using the results of large-scale household surveys, as has been done for India. A third approach involves cross-national analyses of child survival and household fuel use. The fourth method, referred to as the 'fuel-based' approach, which is explored in more depth here, involves applying relative risk estimates from epidemiological studies that use exposure surrogates, such as fuel type, to estimates of household solid fuel use to determine population attributable fractions by disease and age group. With this method and conservative assumptions about relative risks, 4-5 percent of the global LDC totals for both deaths and DALYs (disability adjusted life years) from acute respiratory infections, chronic obstructive pulmonary disease, tuberculosis, asthma, lung cancer, ischaemic heart disease, and blindness can be attributed to solid fuel use in developing countries. Acute respiratory infections in children under five years of age are the largest single category of deaths (64%) and DALYs (81%) from indoor air pollution, apparently being responsible globally for about 1.2 million premature deaths annually in the early 1990s.. indoor air pollution| developing countries| household solid fuel use| risk assessment| global burden of disease|respiratory-infections| daily mortality| exposure| children| health.	AUG-2003	indoor air pollution| developing countries| household solid fuel use| risk assessment| global burden of disease|respiratory-infections| daily mortality| exposure| children| health	Smith, KR; Mehta, S	The burden of disease from indoor air pollution in developing countries: comparison of estimates		INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH	indoor air pollution; developing countries; household solid fuel use; risk assessment; global burden of disease	RESPIRATORY-INFECTIONS; DAILY MORTALITY; EXPOSURE; CHILDREN; HEALTH	Four different methods have been applied to estimate the burden of disease due to indoor air pollution from household solid fuel use in developing countries (LDCs). The largest number of estimates involves applying exposure-response information from urban ambient air pollution studies to estimate indoor exposure concentrations of particulate air pollution. Another approach is to construct child survival curves using the results of large-scale household surveys, as has been done for India. A third approach involves cross-national analyses of child survival and household fuel use. The fourth method, referred to as the 'fuel-based' approach, which is explored in more depth here, involves applying relative risk estimates from epidemiological studies that use exposure surrogates, such as fuel type, to estimates of household solid fuel use to determine population attributable fractions by disease and age group. With this method and conservative assumptions about relative risks, 4-5 percent of the global LDC totals for both deaths and DALYs (disability adjusted life years) from acute respiratory infections, chronic obstructive pulmonary disease, tuberculosis, asthma, lung cancer, ischaemic heart disease, and blindness can be attributed to solid fuel use in developing countries. Acute respiratory infections in children under five years of age are the largest single category of deaths (64%) and DALYs (81%) from indoor air pollution, apparently being responsible globally for about 1.2 million premature deaths annually in the early 1990s.	30	97	2003	11	10.1078/1438-4639-00224	Public, Environmental & Occupational Health; Infectious Diseases
Association of asthma symptoms with peak particulate air pollution and effect modification by anti-inflammatory medication use. Maxima of hourly data from outdoor monitors may capture adverse effects of outdoor particulate matter (PM) exposures in asthmatic children better than do 24-hr PM averages, which form the basis of current regulations in the United States. Also, asthmatic children on anti-inflammatory medications may be protected against the proinflammatory effects of air pollutants and aeroallergens. We examined strengths of pollutant associations with asthma symptoms between subgroups of asthmatic children who were on versus not on regularly scheduled anti-inflammatory medications, and tested associations for different particle averaging times. This is a daily panel study of 22 asthmatic children (9-19 years of age) followed March through April 1996 (1,248 person-days). They lived in nonsmoking households in a semirural area of Southern California within the air inversion mixing zone (range, 1,200-2,100 feet) with transported air pollution from urban areas of Southern California. The dependent variable derived from diary ordinal scores is episodes of asthma symptoms that interfered with daily activities. Minimum to 90th-percentile levels of exposures at the outdoor monitoring site were 12-63 mug/m(3) for 1-hr PM < 10 mum in aerodynamic diameter (PM10); 8-46 mug/m(3) for 8-hr PM10; 7-32 mug/m(3) for 24-hr PM10; 45-88 ppb for 1-hr O-3; 6-26 ppb for 8-hr NO2; 70-4,714 particles/m(3) for 12-hr daytime fungi; and 12-744 particles/m(3) for 24-hr pollen. Data were analyzed with generalized estimating equations controlling for autocorrelation. There was no confounding by weather, day of week, or linear time trend. Associations were notably stronger in 12 asthmatic children who were not taking anti-inflammatory medications versus 10 subjects who were. Odds ratios (95% confidence intervals) for asthma episodes in relation to lag 0 minimum to 90th-percentile pollutant changes were, respectively, 1-hr maximum PM10, 1.92 (1.22-3.02) versus 0.96 (0.25-3.69); 8-hr maximum PM10, 1.68 (0.91-3.09) versus 0.75 (0.18-3.04); 24-hr average PM10, 1.35 (0.82-2.22) versus 0.80 (0.24-2.69); 1-hr maximum O-3, 1.28 (0.75-2.17) versus 0.76 (0.24-2.44); 8-hr maximum NO2, 1.91 (1.07-3.39) versus 1.08 (0.30-3.93); 12-hr fungi, 1.89 (1.24-2.89) versus 0.90 (0.35-2.30); 24-hr pollen, 1.90 (0.99-3.67) versus 0.85 (0.18-3.91). Pollutant associations were stronger during respiratory infections in subjects not on anti-inflammatory medications. Although lag 0 1-hr maximum PM10 showed the strongest association, the most robust associations were for lag 0 and 3-day moving averages (lags 0-2) of 8-hr maximum and 24-hr mean PM10 in sensitivity analyses testing for thresholds. Most pollutant effects were largely driven by concentrations in the upper quintile. The divergence of exposure-response relationships by anti-inflammatory medication use is consistent with experimental data on inflammatory mechanisms of airborne pollutants and allergens.. asthma| epidemiology| longitudinal data analysis| ozone| panel study| particulate air pollution|nitrogen-dioxide| inhaled allergen| southern-california| ozone exposure| hospital admissions| children| responses| pollutants| emergency| mortality.	OCT-2002	asthma| epidemiology| longitudinal data analysis| ozone| panel study| particulate air pollution|nitrogen-dioxide| inhaled allergen| southern-california| ozone exposure| hospital admissions| children| responses| pollutants| emergency| mortality	Delfino, RJ; Zeiger, RS; Seltzer, JM; Street, DH; McLaren, CE	Association of asthma symptoms with peak particulate air pollution and effect modification by anti-inflammatory medication use		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; epidemiology; longitudinal data analysis; ozone; panel study; particulate air pollution	NITROGEN-DIOXIDE; INHALED ALLERGEN; SOUTHERN-CALIFORNIA; OZONE EXPOSURE; HOSPITAL ADMISSIONS; CHILDREN; RESPONSES; POLLUTANTS; EMERGENCY; MORTALITY	Maxima of hourly data from outdoor monitors may capture adverse effects of outdoor particulate matter (PM) exposures in asthmatic children better than do 24-hr PM averages, which form the basis of current regulations in the United States. Also, asthmatic children on anti-inflammatory medications may be protected against the proinflammatory effects of air pollutants and aeroallergens. We examined strengths of pollutant associations with asthma symptoms between subgroups of asthmatic children who were on versus not on regularly scheduled anti-inflammatory medications, and tested associations for different particle averaging times. This is a daily panel study of 22 asthmatic children (9-19 years of age) followed March through April 1996 (1,248 person-days). They lived in nonsmoking households in a semirural area of Southern California within the air inversion mixing zone (range, 1,200-2,100 feet) with transported air pollution from urban areas of Southern California. The dependent variable derived from diary ordinal scores is episodes of asthma symptoms that interfered with daily activities. Minimum to 90th-percentile levels of exposures at the outdoor monitoring site were 12-63 mug/m(3) for 1-hr PM < 10 mum in aerodynamic diameter (PM10); 8-46 mug/m(3) for 8-hr PM10; 7-32 mug/m(3) for 24-hr PM10; 45-88 ppb for 1-hr O-3; 6-26 ppb for 8-hr NO2; 70-4,714 particles/m(3) for 12-hr daytime fungi; and 12-744 particles/m(3) for 24-hr pollen. Data were analyzed with generalized estimating equations controlling for autocorrelation. There was no confounding by weather, day of week, or linear time trend. Associations were notably stronger in 12 asthmatic children who were not taking anti-inflammatory medications versus 10 subjects who were. Odds ratios (95% confidence intervals) for asthma episodes in relation to lag 0 minimum to 90th-percentile pollutant changes were, respectively, 1-hr maximum PM10, 1.92 (1.22-3.02) versus 0.96 (0.25-3.69); 8-hr maximum PM10, 1.68 (0.91-3.09) versus 0.75 (0.18-3.04); 24-hr average PM10, 1.35 (0.82-2.22) versus 0.80 (0.24-2.69); 1-hr maximum O-3, 1.28 (0.75-2.17) versus 0.76 (0.24-2.44); 8-hr maximum NO2, 1.91 (1.07-3.39) versus 1.08 (0.30-3.93); 12-hr fungi, 1.89 (1.24-2.89) versus 0.90 (0.35-2.30); 24-hr pollen, 1.90 (0.99-3.67) versus 0.85 (0.18-3.91). Pollutant associations were stronger during respiratory infections in subjects not on anti-inflammatory medications. Although lag 0 1-hr maximum PM10 showed the strongest association, the most robust associations were for lag 0 and 3-day moving averages (lags 0-2) of 8-hr maximum and 24-hr mean PM10 in sensitivity analyses testing for thresholds. Most pollutant effects were largely driven by concentrations in the upper quintile. The divergence of exposure-response relationships by anti-inflammatory medication use is consistent with experimental data on inflammatory mechanisms of airborne pollutants and allergens.	61	97	2002	11		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin-12: allergen-induced Th2 bias determined at the dendritic cell level. Background The proteolytic activity of the house dust mite allergen Der p 1 has recently been shown to bias Th cell subset development in favour of Th2. Apart from its direct effect on T cells, it is conceivable that the proteolytic activity of Der p 1 may induce the generation of dendritic cells (DCs) that favour a Th2 response. Objective To study the effect of the proteolytic activity of Der p 1 on DC functions; namely cell surface phenotype, IL-12 production and ability to favour a Th2 response. Methods We have generated immature DCs from peripheral blood monocytes, matured them with LPS in the presence of either proteolytically active or inactive Der p 1 and compared their functions using flow cytometric analysis. Results Here we demonstrate for the first time that DCs that have been matured in the presence of proteolytically active Der p 1 produce significantly less IL-12, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. The suppression of IL-12 production was due to the cleavage of CD40 by the proteolytic activity of Der p 1, hence rendering the DCs less responsive to stimulation through the CD40L-CD40 pathway. Furthermore, we demonstrate that DCs that have been matured in the presence of proteolytically active Der p 1 induce the production of significantly less IFN-gamma and more IL-4 by CD4 T cells, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. Conclusions Collectively, our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in directing DCs to induce Th2 subset development.. allergen| dendritic cells| der p 1| th1/th2|cysteine protease activity| t-helper cell| flow-cytometry| antigen| der-p-1| il-12| lymphocytes| capacity| cytokine| requires.	OCT-2002	allergen| dendritic cells| der p 1| th1/th2|cysteine protease activity| t-helper cell| flow-cytometry| antigen| der-p-1| il-12| lymphocytes| capacity| cytokine| requires	Ghaemmaghami, AM; Gough, L; Sewell, HF; Shakib, F	The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin-12: allergen-induced Th2 bias determined at the dendritic cell level		CLINICAL AND EXPERIMENTAL ALLERGY	allergen; dendritic cells; Der p 1; Th1/Th2	CYSTEINE PROTEASE ACTIVITY; T-HELPER CELL; FLOW-CYTOMETRY; ANTIGEN; DER-P-1; IL-12; LYMPHOCYTES; CAPACITY; CYTOKINE; REQUIRES	Background The proteolytic activity of the house dust mite allergen Der p 1 has recently been shown to bias Th cell subset development in favour of Th2. Apart from its direct effect on T cells, it is conceivable that the proteolytic activity of Der p 1 may induce the generation of dendritic cells (DCs) that favour a Th2 response. Objective To study the effect of the proteolytic activity of Der p 1 on DC functions; namely cell surface phenotype, IL-12 production and ability to favour a Th2 response. Methods We have generated immature DCs from peripheral blood monocytes, matured them with LPS in the presence of either proteolytically active or inactive Der p 1 and compared their functions using flow cytometric analysis. Results Here we demonstrate for the first time that DCs that have been matured in the presence of proteolytically active Der p 1 produce significantly less IL-12, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. The suppression of IL-12 production was due to the cleavage of CD40 by the proteolytic activity of Der p 1, hence rendering the DCs less responsive to stimulation through the CD40L-CD40 pathway. Furthermore, we demonstrate that DCs that have been matured in the presence of proteolytically active Der p 1 induce the production of significantly less IFN-gamma and more IL-4 by CD4 T cells, compared to DCs that have been matured in the presence of proteolytically inactive Der p 1. Conclusions Collectively, our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in directing DCs to induce Th2 subset development.	24	97	2002	8	10.1046/j.1365-2745.2002.01504.x	Allergy; Immunology
Multistep navigation of Langerhans/dendritic cells in and out of the skin. Langerhans cells (LCs) are specialized antigen-presenting cells that reside in the epidermis as sentinels of the immune system. LCs constantly monitor the epidermal microenvironment by taking up antigen and processing it into fragments that can be recognized by cells of the adaptive immune response. Because of their unique migratory ability, LCs can transport antigen from the epidermis to regional lymph nodes, where they can initiate systemic immune responses. The mechanisms of LC trafficking thus seem to be of particular relevance for the induction and maintenance of cutaneous immunity. LCs or their putative precursors express surface molecules that allow them to home to skin and localize in the epidermis for prolonged periods of time. Tissue injury, microbial infection, and other perturbants of epidermal homeostasis (eg, contact allergens) provide danger signals, leading to a local production of proinflammatory cytokines that induce LC mobilization to the lymphoid tissue. At the same time, signals are generated that recruit LC precursors into the skin to maintain the epidermal LC population. Distinct pairs of chemokines and their receptors control the migration from blood to epidermis and from there to the regional lymphatics. In addition, trafficking is controlled at the level of cell adhesion, where LCs downregulate some adhesion molecules to exit the epidermis and upregulate others to migrate across the extracellular matrix and home to T-cell areas of regional lymphoid tissue. The improved understanding of mechanisms that regulate LC trafficking might offer new opportunities for therapeutic interventions to suppress, stimulate, or deviate cutaneous immune responses.. langerhans cells| dendritic cells| migration-trafficking| adhesion| chemokines| skin| allergy| immune regulation|human peripheral-blood| cpg-containing oligodeoxynucleotides| inflammatory protein 3-alpha| cadherin-mediated adhesion| cutaneous dendritic cells| necrosis-factor-alpha| draining lymph-nodes| contact hypersensitivity| chemokine receptors| th1 responses.	NOV-2001	langerhans cells| dendritic cells| migration-trafficking| adhesion| chemokines| skin| allergy| immune regulation|human peripheral-blood| cpg-containing oligodeoxynucleotides| inflammatory protein 3-alpha| cadherin-mediated adhesion| cutaneous dendritic cells| necrosis-factor-alpha| draining lymph-nodes| contact hypersensitivity| chemokine receptors| th1 responses	Jakob, T; Ring, J; Udey, MC	Multistep navigation of Langerhans/dendritic cells in and out of the skin		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Langerhans cells; dendritic cells; migration-trafficking; adhesion; chemokines; skin; allergy; immune regulation	HUMAN PERIPHERAL-BLOOD; CPG-CONTAINING OLIGODEOXYNUCLEOTIDES; INFLAMMATORY PROTEIN 3-ALPHA; CADHERIN-MEDIATED ADHESION; CUTANEOUS DENDRITIC CELLS; NECROSIS-FACTOR-ALPHA; DRAINING LYMPH-NODES; CONTACT HYPERSENSITIVITY; CHEMOKINE RECEPTORS; TH1 RESPONSES	Langerhans cells (LCs) are specialized antigen-presenting cells that reside in the epidermis as sentinels of the immune system. LCs constantly monitor the epidermal microenvironment by taking up antigen and processing it into fragments that can be recognized by cells of the adaptive immune response. Because of their unique migratory ability, LCs can transport antigen from the epidermis to regional lymph nodes, where they can initiate systemic immune responses. The mechanisms of LC trafficking thus seem to be of particular relevance for the induction and maintenance of cutaneous immunity. LCs or their putative precursors express surface molecules that allow them to home to skin and localize in the epidermis for prolonged periods of time. Tissue injury, microbial infection, and other perturbants of epidermal homeostasis (eg, contact allergens) provide danger signals, leading to a local production of proinflammatory cytokines that induce LC mobilization to the lymphoid tissue. At the same time, signals are generated that recruit LC precursors into the skin to maintain the epidermal LC population. Distinct pairs of chemokines and their receptors control the migration from blood to epidermis and from there to the regional lymphatics. In addition, trafficking is controlled at the level of cell adhesion, where LCs downregulate some adhesion molecules to exit the epidermis and upregulate others to migrate across the extracellular matrix and home to T-cell areas of regional lymphoid tissue. The improved understanding of mechanisms that regulate LC trafficking might offer new opportunities for therapeutic interventions to suppress, stimulate, or deviate cutaneous immune responses.	66	97	2001	9		Allergy; Immunology
Oxidant-mediated lung epithelial cell tolerance: the role of intracellular glutathione and nuclear factor-kappaB. The airway epithelium is injured by oxidants inhaled as atmospheric pollutants or produced during inflammatory responses. We studied the effect of modulating the antioxidant intracellular glutathione, both using thiol compounds and by the adaptive effect of hyperoxia, on oxidant-induced injury and activation of the nuclear factor-kappaB (NF-kappaB) in two cell lines: the human bronchial (16HBE) and type II alveolar epithelial cells (A549). The thiol antioxidants glutathione (GSH) and glutathione monoethyl ester (GSH-MEE) [2 mM] increased GSH levels (nmol/mg protein) in A549 cells (GSH 383 +/- 26 and GSH-MEE 336 +/- 23 vs control 171 +/- 13, P < 0.001) and in 16HBE cells (GSH 405 +/- 33, GSH-MEE 362 +/- 37 vs control 198 +/- 12, P < 0.001, N = 3). Treatment of hyperoxia (95% oxygen) also increased GSH levels between 4 and 24 hr exposure compared with control (P < 0.01). Hydrogen peroxide (H2O2) (0.01 mM) induced NF-kappaB activation, whereas hyperoxia exposure did not affect NF-kappaB activation in either cell line. Pretreatment with DL-buthionine (SR)sulfoximine, which decreased intracellular glutathione, increased NF-kappaB binding induced by H2O2 and increased lactate dehydrogenase (LDH) release (P < 0.001). Pretreatment with the thiol compounds and hyperoxia totally inhibited H2O2-induced NF-kappaB binding and cell injury as measured by LDH release. These data indicate the importance of intracellular glutathione and inhibition of NF-kappaB in both protection/tolerance against oxidant-induced epithelial cell injury, and NF-kappaB activation in response to oxidative stress which may be important in lung inflammation. Thus, increasing intracellular glutathione may be of therapeutic relevance if able to modulate NF-kappaB activation and hence attenuate inflammation. (C) 2001 Elsevier Science Inc. All rights reserved.. gsh| nf-kappa b| hyperoxia| tolerance| 16hbe| a549|necrosis-factor-alpha| transcription factor| signal-transduction| induced apoptosis| oxidative stress| b activation| inflammation| asthma| interleukin-8| dexamethasone.	SEP 15-2001	gsh| nf-kappa b| hyperoxia| tolerance| 16hbe| a549|necrosis-factor-alpha| transcription factor| signal-transduction| induced apoptosis| oxidative stress| b activation| inflammation| asthma| interleukin-8| dexamethasone	Rahman, I; Mulier, B; Gilmour, PS; Watchorn, T; Donaldson, K; Jeffery, PK; MacNee, W	Oxidant-mediated lung epithelial cell tolerance: the role of intracellular glutathione and nuclear factor-kappaB		BIOCHEMICAL PHARMACOLOGY	GSH; NF-kappa B; hyperoxia; tolerance; 16HBE; A549	NECROSIS-FACTOR-ALPHA; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; OXIDATIVE STRESS; B ACTIVATION; INFLAMMATION; ASTHMA; INTERLEUKIN-8; DEXAMETHASONE	The airway epithelium is injured by oxidants inhaled as atmospheric pollutants or produced during inflammatory responses. We studied the effect of modulating the antioxidant intracellular glutathione, both using thiol compounds and by the adaptive effect of hyperoxia, on oxidant-induced injury and activation of the nuclear factor-kappaB (NF-kappaB) in two cell lines: the human bronchial (16HBE) and type II alveolar epithelial cells (A549). The thiol antioxidants glutathione (GSH) and glutathione monoethyl ester (GSH-MEE) [2 mM] increased GSH levels (nmol/mg protein) in A549 cells (GSH 383 +/- 26 and GSH-MEE 336 +/- 23 vs control 171 +/- 13, P < 0.001) and in 16HBE cells (GSH 405 +/- 33, GSH-MEE 362 +/- 37 vs control 198 +/- 12, P < 0.001, N = 3). Treatment of hyperoxia (95% oxygen) also increased GSH levels between 4 and 24 hr exposure compared with control (P < 0.01). Hydrogen peroxide (H2O2) (0.01 mM) induced NF-kappaB activation, whereas hyperoxia exposure did not affect NF-kappaB activation in either cell line. Pretreatment with DL-buthionine (SR)sulfoximine, which decreased intracellular glutathione, increased NF-kappaB binding induced by H2O2 and increased lactate dehydrogenase (LDH) release (P < 0.001). Pretreatment with the thiol compounds and hyperoxia totally inhibited H2O2-induced NF-kappaB binding and cell injury as measured by LDH release. These data indicate the importance of intracellular glutathione and inhibition of NF-kappaB in both protection/tolerance against oxidant-induced epithelial cell injury, and NF-kappaB activation in response to oxidative stress which may be important in lung inflammation. Thus, increasing intracellular glutathione may be of therapeutic relevance if able to modulate NF-kappaB activation and hence attenuate inflammation. (C) 2001 Elsevier Science Inc. All rights reserved.	38	97	2001	8	10.1016/S0006-2952(01)00702-X	Pharmacology & Pharmacy
Peak flow diaries in childhood asthma are unreliable. Background-A study was undertaken to investigate the compliance with and accuracy of peak flow diaries in childhood asthma. Methods-Forty asthmatic children (5-16 years) were asked to perform peak flow measurements twice daily for 4 weeks by means of an electronic peak flow meter and to record values in a written diary. Patients and parents were unaware that the device stored the peak flow values on a microchip. In random order, half of the patients were only told that the device allowed for more accurate assessment of peak flow while the other half were told that accurate recording of peak flow was important because the results would be used in guiding adjustments to treatment. Data in the written diary (reported data) were compared with those from the electronic diary tactual data). Results-In the entire study population the mean (SD) actual compliance (77.1 (20.5)%) was much lower than the mean reported compliance (95.7 (9.1)%) (95% CI for difference 12.7% to 24.4%) The percentage of correct peak flow entries decreased from 56% to <50% from the first to the last study week (p<0.04), mainly as a result of an increase in self-invented peak flow entries. Results were comparable for both groups. For incorrect peak flow entries the mean difference between written and electronically recorded entries ranged from -72 to 34 l/min per patient. Conclusions-Peak how diaries kept by asthmatic children are unreliable. Electronic peak flow meters should be used if peak how monitoring is required in children with asthma.. asthma| children| home monitoring| peak expiratory flow| compliance|home management| inner-city| children.	MAR-2001	asthma| children| home monitoring| peak expiratory flow| compliance|home management| inner-city| children	Kamps, AWA; Roorda, RJ; Brand, PLP	Peak flow diaries in childhood asthma are unreliable		THORAX	asthma; children; home monitoring; peak expiratory flow; compliance	HOME MANAGEMENT; INNER-CITY; CHILDREN	Background-A study was undertaken to investigate the compliance with and accuracy of peak flow diaries in childhood asthma. Methods-Forty asthmatic children (5-16 years) were asked to perform peak flow measurements twice daily for 4 weeks by means of an electronic peak flow meter and to record values in a written diary. Patients and parents were unaware that the device stored the peak flow values on a microchip. In random order, half of the patients were only told that the device allowed for more accurate assessment of peak flow while the other half were told that accurate recording of peak flow was important because the results would be used in guiding adjustments to treatment. Data in the written diary (reported data) were compared with those from the electronic diary tactual data). Results-In the entire study population the mean (SD) actual compliance (77.1 (20.5)%) was much lower than the mean reported compliance (95.7 (9.1)%) (95% CI for difference 12.7% to 24.4%) The percentage of correct peak flow entries decreased from 56% to <50% from the first to the last study week (p<0.04), mainly as a result of an increase in self-invented peak flow entries. Results were comparable for both groups. For incorrect peak flow entries the mean difference between written and electronically recorded entries ranged from -72 to 34 l/min per patient. Conclusions-Peak how diaries kept by asthmatic children are unreliable. Electronic peak flow meters should be used if peak how monitoring is required in children with asthma.	10	97	2001	3	10.1136/thorax.56.3.180	Respiratory System
Increasing prevalence of specific IgE to aeroallergens in an adult population: Two cross-sectional surveys 8 years apart - The Copenhagen Allergy Study. Background: There is evidence that the prevalence of respiratory allergy has increased in children in many countries. However, this evidence is largely based on questionnaire data, and little is known about similar trends in adults. Objective: We investigated whether the prevalence of specific IgE to aeroallergens had increased in an adult general population over an 8-year period. Methods: Two cross-sectional surveys were carried out in 1990 and 1998, A mailed screening questionnaire on respiratory symptoms sent to random samples of 15- to 41-year-old subjects living in Copenhagen (Denmark) preceded both surveys. Random samples of responders were invited to a health examination, including assessment of specific IgE to 6 common aeroallergens. Totals of 312 (74.6% of the invited subjects) and 482 (53.4% of the invited subjects) subjects were examined in 1990 and 1998, respectively, Analyses of serum samples from both surveys were performed in 1999, Results: The prevalence of specific IgE to at least one allergen increased significantly from 1990 to 1998 (26.5% vs 33.9%; odds ratio adjusted for sex, age, and season of examination, 1.63; 95% confidence interval, 1.15-2.32; P = .006), This increase remained unexplained after adjustment for changes in questionnaire variables on lifestyle and home environment, The clinical significance of this increase was underlined by a corresponding increase in the prevalence of allergic rhinitis symptoms associated with specific IgE positivity, Conclusion: We found that the prevalence of specific IgE positivity to aeroallergens increased in an adult Danish general population from 1990 and 1998.. adult| epidemiology| prevalence| respiratory hypersensitivity| specific ige positivity| specific ige stability|skin-test reactivity| changing prevalence| danish population| hay-fever| rhinitis| asthma| children| antibodies| diagnosis| symptoms.	AUG-2000	adult| epidemiology| prevalence| respiratory hypersensitivity| specific ige positivity| specific ige stability|skin-test reactivity| changing prevalence| danish population| hay-fever| rhinitis| asthma| children| antibodies| diagnosis| symptoms	Linneberg, A; Nielsen, NH; Madsen, F; Frolund, L; Dirksen, A; Jorgensen, T	Increasing prevalence of specific IgE to aeroallergens in an adult population: Two cross-sectional surveys 8 years apart - The Copenhagen Allergy Study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	adult; epidemiology; prevalence; respiratory hypersensitivity; specific IgE positivity; specific IgE stability	SKIN-TEST REACTIVITY; CHANGING PREVALENCE; DANISH POPULATION; HAY-FEVER; RHINITIS; ASTHMA; CHILDREN; ANTIBODIES; DIAGNOSIS; SYMPTOMS	Background: There is evidence that the prevalence of respiratory allergy has increased in children in many countries. However, this evidence is largely based on questionnaire data, and little is known about similar trends in adults. Objective: We investigated whether the prevalence of specific IgE to aeroallergens had increased in an adult general population over an 8-year period. Methods: Two cross-sectional surveys were carried out in 1990 and 1998, A mailed screening questionnaire on respiratory symptoms sent to random samples of 15- to 41-year-old subjects living in Copenhagen (Denmark) preceded both surveys. Random samples of responders were invited to a health examination, including assessment of specific IgE to 6 common aeroallergens. Totals of 312 (74.6% of the invited subjects) and 482 (53.4% of the invited subjects) subjects were examined in 1990 and 1998, respectively, Analyses of serum samples from both surveys were performed in 1999, Results: The prevalence of specific IgE to at least one allergen increased significantly from 1990 to 1998 (26.5% vs 33.9%; odds ratio adjusted for sex, age, and season of examination, 1.63; 95% confidence interval, 1.15-2.32; P = .006), This increase remained unexplained after adjustment for changes in questionnaire variables on lifestyle and home environment, The clinical significance of this increase was underlined by a corresponding increase in the prevalence of allergic rhinitis symptoms associated with specific IgE positivity, Conclusion: We found that the prevalence of specific IgE positivity to aeroallergens increased in an adult Danish general population from 1990 and 1998.	20	97	2000	6	10.1067/mai.2000.108312	Allergy; Immunology
First-line therapy for adult patients with acute asthma receiving a multiple-bose protocol of ipratropium bromide plus albuterol in the emergency department. We designed a larger, double-blind, randomized, prospective trial to test our hypothesis that patients with acute asthma given combination high dose therapy with ipratropium bromide (IB) and beta(2)-agonists will have greater improvement in pulmonary function and fewer hospital admissions than those given beta(2)-agonists alone. One hundred eighty patients (mean age +/- SD, 34.3 +/- 10.5 yr) who presented to an emergency department (ED) for treatment of an exacerbation of asthma (baseline FEV1 < 50% of predicted) were assigned in a randomized, double-blind fashion to receive albuterol and placebo (n = 92) or albuterol and IB (n = 88). Both drugs were administered through a metered-dose inhaler and spacer at 10-min intervals for 3 h (24 puffs or 2,880 mu g of albuterol and 504 mu g of IB each hour). Primary outcome measures were improvement in pulmonary function (FEV1 or peak expiratory flow [PEF]), and hospital admission rates. In both groups, pulmonary function improved significantly over baseline values (p < 0.01). Subjects who received IB had an overall 20.5% (95% CI: 2.6 to 38.4%) (p = 0.02) greater improvement in PEF and a 48.1% (95% CI: 19.8 to 76.4%) (p = 0.001) greater improvement in FEV1 from the control group. At the end of protocol (3 h), 39% (n = 36) of patients in the control group and 20% (n = 18) in the IB group were admitted (p = 0.01). The use of high doses of is reduced the risk of hospital admission 49% (relative risk = 0.51, 95% CI: 0.31 to 0.83). Five (95% CI: 3 to 17) patients would need to be treated with high doses of IB to prevent a single admission. Kaplan-Meier-estimated curves of the proportion of patients who reached the discharge threshold during the 3 h of treatment, showed a significant difference in favor of the IB group (log-rank test = 0.005). A subgroup analysis showed that patients most likely to benefit from the addition of high doses of IB were those with more severe obstruction (FEV1 less than or equal to 30% of predicted) and long duration of symptoms before the ED presentation (greater than or equal to 24 h). On the contrary, previous use of inhaled beta(2)-agonists did not modify the admission rate and the pulmonary function response to IB. In conclusion, our data support a substantial therapeutic benefit from the addition of IB to albuterol administered in high doses through MDI plus spacer, particularly in patients with FEV1 less than 30%, and with long duration of symptoms before the ED presentation (greater than or equal to 24 h).. air-flow obstruction| nebulized ipratropium| salbutamol| children| metaanalysis| management| efficacy| bronchodilator| childhood| agonists.	JUN-2000	air-flow obstruction| nebulized ipratropium| salbutamol| children| metaanalysis| management| efficacy| bronchodilator| childhood| agonists	Rodrigo, CJ; Rodrigo, C	First-line therapy for adult patients with acute asthma receiving a multiple-bose protocol of ipratropium bromide plus albuterol in the emergency department		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		AIR-FLOW OBSTRUCTION; NEBULIZED IPRATROPIUM; SALBUTAMOL; CHILDREN; METAANALYSIS; MANAGEMENT; EFFICACY; BRONCHODILATOR; CHILDHOOD; AGONISTS	We designed a larger, double-blind, randomized, prospective trial to test our hypothesis that patients with acute asthma given combination high dose therapy with ipratropium bromide (IB) and beta(2)-agonists will have greater improvement in pulmonary function and fewer hospital admissions than those given beta(2)-agonists alone. One hundred eighty patients (mean age +/- SD, 34.3 +/- 10.5 yr) who presented to an emergency department (ED) for treatment of an exacerbation of asthma (baseline FEV1 < 50% of predicted) were assigned in a randomized, double-blind fashion to receive albuterol and placebo (n = 92) or albuterol and IB (n = 88). Both drugs were administered through a metered-dose inhaler and spacer at 10-min intervals for 3 h (24 puffs or 2,880 mu g of albuterol and 504 mu g of IB each hour). Primary outcome measures were improvement in pulmonary function (FEV1 or peak expiratory flow [PEF]), and hospital admission rates. In both groups, pulmonary function improved significantly over baseline values (p < 0.01). Subjects who received IB had an overall 20.5% (95% CI: 2.6 to 38.4%) (p = 0.02) greater improvement in PEF and a 48.1% (95% CI: 19.8 to 76.4%) (p = 0.001) greater improvement in FEV1 from the control group. At the end of protocol (3 h), 39% (n = 36) of patients in the control group and 20% (n = 18) in the IB group were admitted (p = 0.01). The use of high doses of is reduced the risk of hospital admission 49% (relative risk = 0.51, 95% CI: 0.31 to 0.83). Five (95% CI: 3 to 17) patients would need to be treated with high doses of IB to prevent a single admission. Kaplan-Meier-estimated curves of the proportion of patients who reached the discharge threshold during the 3 h of treatment, showed a significant difference in favor of the IB group (log-rank test = 0.005). A subgroup analysis showed that patients most likely to benefit from the addition of high doses of IB were those with more severe obstruction (FEV1 less than or equal to 30% of predicted) and long duration of symptoms before the ED presentation (greater than or equal to 24 h). On the contrary, previous use of inhaled beta(2)-agonists did not modify the admission rate and the pulmonary function response to IB. In conclusion, our data support a substantial therapeutic benefit from the addition of IB to albuterol administered in high doses through MDI plus spacer, particularly in patients with FEV1 less than 30%, and with long duration of symptoms before the ED presentation (greater than or equal to 24 h).	29	97	2000	7		General & Internal Medicine; Respiratory System
Clara cell secretory protein (CC16): Features as a peripheral lung biomarker. Clara cell protein (CC16 or CC10) is a 15.8-kDa protein secreted all along the tracheobronchial tree and especially in the terminal bronchioles where Clara cells are localized. Even though the exact in vivo function of CC16 remains to be clarified, evidence is accumulating that CC16 plays an important protective role in the respiratory tract against oxidative stress and inflammatory response. CC16, however, presents also a major interest as a peripheral lung marker for assessing the cellular integrity or the permeability of the lung epithelium. The serum concentrations of CC16 are decreased in subjects with chronic lung damage caused by tobacco smoke and other air pollutants as a consequence of the destruction of Clara cells. By contrast, serum CC16 in. creases in acute or chronic lung disorders characterized by an increased airways permeability. The sensitivity of serum CC16 to an increased leakiness of the lung allows for the detection of defects of the epithelial barrier at ozone levels below current air-quality guidelines. Although the clinical significance of these early epithelial changes detected by serum CC16 remains to be determined, these results clearly show that the assay in serum of lung secretory proteins such as CC16 represents a new noninvasive approach to evaluate the integrity of the respiratory tract.. bronchoalveolar lavage| biological-fluids| 10-kda protein| serum levels| asthma| epithelium| permeability| polymorphism| uteroglobin| marker.	2000	bronchoalveolar lavage| biological-fluids| 10-kda protein| serum levels| asthma| epithelium| permeability| polymorphism| uteroglobin| marker	Broeckaert, F; Clippe, A; Knoops, B; Hermans, C; Bernard, A	Clara cell secretory protein (CC16): Features as a peripheral lung biomarker		UTEROGLOBIN/CLARA CELL PROTEIN FAMILY		BRONCHOALVEOLAR LAVAGE; BIOLOGICAL-FLUIDS; 10-KDA PROTEIN; SERUM LEVELS; ASTHMA; EPITHELIUM; PERMEABILITY; POLYMORPHISM; UTEROGLOBIN; MARKER	Clara cell protein (CC16 or CC10) is a 15.8-kDa protein secreted all along the tracheobronchial tree and especially in the terminal bronchioles where Clara cells are localized. Even though the exact in vivo function of CC16 remains to be clarified, evidence is accumulating that CC16 plays an important protective role in the respiratory tract against oxidative stress and inflammatory response. CC16, however, presents also a major interest as a peripheral lung marker for assessing the cellular integrity or the permeability of the lung epithelium. The serum concentrations of CC16 are decreased in subjects with chronic lung damage caused by tobacco smoke and other air pollutants as a consequence of the destruction of Clara cells. By contrast, serum CC16 in. creases in acute or chronic lung disorders characterized by an increased airways permeability. The sensitivity of serum CC16 to an increased leakiness of the lung allows for the detection of defects of the epithelial barrier at ozone levels below current air-quality guidelines. Although the clinical significance of these early epithelial changes detected by serum CC16 remains to be determined, these results clearly show that the assay in serum of lung secretory proteins such as CC16 represents a new noninvasive approach to evaluate the integrity of the respiratory tract.	29	97	2000	10		Biochemistry & Molecular Biology; Science & Technology - Other Topics
Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. BACKGROUND Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. METHODS We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 >= 80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. RESULTS Among 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (+/- SD) decline of 53 +/- 21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27 +/- 18 ml per year (P<0.001), despite similar smoking exposure. CONCLUSIONS Our study suggests that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.). air-flow obstruction| forced expiratory volume| function decline| natural-history| inhaled budesonide| childhood asthma| controlled-trial| cohort| copd| smoking.	JUL 9-2015	air-flow obstruction| forced expiratory volume| function decline| natural-history| inhaled budesonide| childhood asthma| controlled-trial| cohort| copd| smoking	Lange, P; Celli, B; Agusti, A; Jensen, GB; Divo, M; Faner, R; Guerra, S; Marott, JL; Martinez, FD; Martinez-Camblor, P; Meek, P; Owen, CA; Petersen, H; Pinto-Plata, V; Schnohr, P; Sood, A; Soriano, JB; Tesfaigzi, Y; Vestbo, J	Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease		NEW ENGLAND JOURNAL OF MEDICINE		AIR-FLOW OBSTRUCTION; FORCED EXPIRATORY VOLUME; FUNCTION DECLINE; NATURAL-HISTORY; INHALED BUDESONIDE; CHILDHOOD ASTHMA; CONTROLLED-TRIAL; COHORT; COPD; SMOKING	BACKGROUND Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. METHODS We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 >= 80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. RESULTS Among 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (+/- SD) decline of 53 +/- 21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27 +/- 18 ml per year (P<0.001), despite similar smoking exposure. CONCLUSIONS Our study suggests that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1 is not an obligate feature of COPD. (Funded by an unrestricted grant from GlaxoSmithKline and others.)	36	96	2015	12	10.1056/NEJMoa1411532	General & Internal Medicine
"Increased serum IL-17 is an independent risk factor for severe asthma. Background: IL-17 expression was found to be associated with many inflammatory diseases in humans, such as rheumatoid arthritis, asthma, systemic lupus erythematosus and allograft rejection and many in vitro studies have indicated a proinflammatory function for IL-17. Objective: Prognostic value of increased serum IL-17 in asthma patients. Methods: Serum IL-17 (ELISA) was measured in 85 asthma patients (pts), mean age 46.99 +/- 14.1 years, 61% females, 23 mild persistent, 26 moderate persistent and 36 severe persistent asthma. Using multiple regression analysis (STATISTICA 7), increased serum IL-17 (>20 pg/ml) was tested as risk factor for severe asthma in comparison with ""traditional"" risk factors: smoke, NSAID intolerance, obesity, chronic rhinosinusitis, blood eosinophilia, FEV(1) at baseline < 50% predicted (low FEV(1)). Results: Medium serum IL-17 values were 14.21 pg/ml in mild asthma, 12.22 pg/ml in moderate asthma and 24.72 pg/ml in severe asthma. IL-17 values > 20 pg/ml were encountered in 3(13%) mild asthma pts (p < 0.001 vs. severe asthma), 2(8%) moderate asthma pts. (p < 0.001 vs. severe asthma), and in 11(31%) severe asthma pts. For severe asthma multiple regression analysis revealed as independent risk factors IL-17 (p = 0.000290), NSAID intolerance (p = 0.000585) and low FEV(1) (p = 0.000059). Conclusions: IL-17 is increased in severe asthma compared to mild/moderate forms of the disease and values above 20 pg/ml are an independent risk factor for severe asthma. (C) 2010 Elsevier Ltd. All rights reserved.. il-17| severe asthma| risk factors|c-reactive protein| air-flow limitation| cells| th17| inflammation| sputum."	AUG-2010	il-17| severe asthma| risk factors|c-reactive protein| air-flow limitation| cells| th17| inflammation| sputum	Agache, I; Ciobanu, C; Agache, C; Anghel, M	Increased serum IL-17 is an independent risk factor for severe asthma		RESPIRATORY MEDICINE	IL-17; Severe asthma; Risk factors	C-REACTIVE PROTEIN; AIR-FLOW LIMITATION; CELLS; TH17; INFLAMMATION; SPUTUM	"Background: IL-17 expression was found to be associated with many inflammatory diseases in humans, such as rheumatoid arthritis, asthma, systemic lupus erythematosus and allograft rejection and many in vitro studies have indicated a proinflammatory function for IL-17. Objective: Prognostic value of increased serum IL-17 in asthma patients. Methods: Serum IL-17 (ELISA) was measured in 85 asthma patients (pts), mean age 46.99 +/- 14.1 years, 61% females, 23 mild persistent, 26 moderate persistent and 36 severe persistent asthma. Using multiple regression analysis (STATISTICA 7), increased serum IL-17 (>20 pg/ml) was tested as risk factor for severe asthma in comparison with ""traditional"" risk factors: smoke, NSAID intolerance, obesity, chronic rhinosinusitis, blood eosinophilia, FEV(1) at baseline < 50% predicted (low FEV(1)). Results: Medium serum IL-17 values were 14.21 pg/ml in mild asthma, 12.22 pg/ml in moderate asthma and 24.72 pg/ml in severe asthma. IL-17 values > 20 pg/ml were encountered in 3(13%) mild asthma pts (p < 0.001 vs. severe asthma), 2(8%) moderate asthma pts. (p < 0.001 vs. severe asthma), and in 11(31%) severe asthma pts. For severe asthma multiple regression analysis revealed as independent risk factors IL-17 (p = 0.000290), NSAID intolerance (p = 0.000585) and low FEV(1) (p = 0.000059). Conclusions: IL-17 is increased in severe asthma compared to mild/moderate forms of the disease and values above 20 pg/ml are an independent risk factor for severe asthma. (C) 2010 Elsevier Ltd. All rights reserved."	15	96	2010	7	10.1016/j.rmed.2010.02.018	Cardiovascular System & Cardiology; Respiratory System
Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis. Atopic dermatitis (AD) is a common chronic relapsing pruritic skin disease of dogs for which treatment has varied over time and geographical location. Recent high quality randomized controlled trials and systematic reviews have established which drugs are likely to offer consistent benefit. The International Task Force for Canine AD currently recommends a multifaceted approach to treat dogs with AD. Acute flares should be treated with a combination of nonirritating baths and topical glucocorticoids, once an attempt has been made to identify and remove the suspected causes of the flare. Oral glucocorticoids and antimicrobial therapy must be added when needed. In dogs with chronic AD, a combination of interventions should be considered. Again, factors that trigger flares of AD must be identified and, if possible, avoided. Currently recognized flare factors include food, flea and environmental allergens, Staphylococcus bacteria and Malassezia yeast. Skin and coat hygiene and care must be improved by bathing with nonirritating shampoos and dietary supplementation with essential fatty acids. The severity of pruritus and skin lesions can be reduced with a combination of anti-inflammatory drugs. Currently, medications with good evidence of high efficacy include topical and oral glucocorticoids, and calcineurin inhibitors such as oral ciclosporin and topical tacrolimus. The dose and frequency of administration of these drugs should be tailored to each patient considering each drug's efficacy, adverse effects and cost. Allergen-specific immunotherapy should be offered, whenever feasible, in an attempt to prevent recurrence of clinical signs upon further exposure to environmental allergens to which the patient is hypersensitive.. allergen-specific immunotherapy| house-dust mites| type-1 hypersensitivity reactions| adverse food reactions| double-blind| tacrolimus ointment| healthy dogs| controlled-trial| malassezia-pachydermatis| fluticasone propionate.	JUN-2010	allergen-specific immunotherapy| house-dust mites| type-1 hypersensitivity reactions| adverse food reactions| double-blind| tacrolimus ointment| healthy dogs| controlled-trial| malassezia-pachydermatis| fluticasone propionate	Olivry, T; DeBoer, DJ; Favrot, C; Jackson, HA; Mueller, RS; Nuttall, T; Prelaud, P	Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis		VETERINARY DERMATOLOGY		ALLERGEN-SPECIFIC IMMUNOTHERAPY; HOUSE-DUST MITES; TYPE-1 HYPERSENSITIVITY REACTIONS; ADVERSE FOOD REACTIONS; DOUBLE-BLIND; TACROLIMUS OINTMENT; HEALTHY DOGS; CONTROLLED-TRIAL; MALASSEZIA-PACHYDERMATIS; FLUTICASONE PROPIONATE	Atopic dermatitis (AD) is a common chronic relapsing pruritic skin disease of dogs for which treatment has varied over time and geographical location. Recent high quality randomized controlled trials and systematic reviews have established which drugs are likely to offer consistent benefit. The International Task Force for Canine AD currently recommends a multifaceted approach to treat dogs with AD. Acute flares should be treated with a combination of nonirritating baths and topical glucocorticoids, once an attempt has been made to identify and remove the suspected causes of the flare. Oral glucocorticoids and antimicrobial therapy must be added when needed. In dogs with chronic AD, a combination of interventions should be considered. Again, factors that trigger flares of AD must be identified and, if possible, avoided. Currently recognized flare factors include food, flea and environmental allergens, Staphylococcus bacteria and Malassezia yeast. Skin and coat hygiene and care must be improved by bathing with nonirritating shampoos and dietary supplementation with essential fatty acids. The severity of pruritus and skin lesions can be reduced with a combination of anti-inflammatory drugs. Currently, medications with good evidence of high efficacy include topical and oral glucocorticoids, and calcineurin inhibitors such as oral ciclosporin and topical tacrolimus. The dose and frequency of administration of these drugs should be tailored to each patient considering each drug's efficacy, adverse effects and cost. Allergen-specific immunotherapy should be offered, whenever feasible, in an attempt to prevent recurrence of clinical signs upon further exposure to environmental allergens to which the patient is hypersensitive.	74	96	2010	16	10.1111/j.1365-3164.2010.00889.x	Dermatology; Veterinary Sciences
Phthalate exposure and asthma in children. P>During the last decades more than 100 000 new chemicals have been introduced to the environment. Many of these new chemicals and many common consumer products that include these have been shown to be toxic in animal studies and an increasing body of evidence suggests that they are also impacting human health. Among the suspect chemicals, the endocrine disrupting chemicals (EDCs) are of particular concern. One such chemical group is the phthalates, used in soft poly vinyl chloride (PVC) material and in a huge number of consumer products. During the same period of time that the prevalence of these modern chemicals has increased, there has been a remarkable increase in several chronic illnesses, including asthma and allergy in children. In this article we outline the scientific knowledge on phthalate exposure for asthma and airway diseases in children by examining epidemiological and experimental peer review data for potential explanatory mechanisms. Epidemiological data point to a possible correlation between phthalate exposure and asthma and airway diseases in children. Experimental studies present support for an adjuvant effect on basic mechanisms in allergic sensitization by several phthalates. Despite variations in the experimental design and reported result in the individual studies, a majority of published reports have identified adjuvant effects on Th2 differentiation, production of Th2 cytokines and enhanced levels of Th2 promoted immunoglobulins (mainly IgG1 but also IgE) in mice. A limited amount of data do also suggest phthalate-induced enhancement of mast cell degranulation and eosinophilic infiltration which are important parts in the early inflammation phase. Thus, some of the early key mechanisms in the pathology of allergic asthma could possibly be targeted by phthalate exposure. But the important questions of clinical relevance of real life exposure and identification of molecular targets that can explain interactions largely remain to be answered.. asthma| endocrine disrupters| environmental factors| epidemiology| immunology|subcutaneous injection model| endocrine-disrupting chemicals| in-house dust| di-n-butyl| di-(2-ethylhexyl) phthalate| balb/c mice| di(2-ethylhexyl) phthalate| airway inflammation| young-children| mono-2-ethylhexyl phthalate.	APR-2010	asthma| endocrine disrupters| environmental factors| epidemiology| immunology|subcutaneous injection model| endocrine-disrupting chemicals| in-house dust| di-n-butyl| di-(2-ethylhexyl) phthalate| balb/c mice| di(2-ethylhexyl) phthalate| airway inflammation| young-children| mono-2-ethylhexyl phthalate	Bornehag, CG; Nanberg, E	Phthalate exposure and asthma in children		INTERNATIONAL JOURNAL OF ANDROLOGY	asthma; endocrine disrupters; environmental factors; epidemiology; immunology	SUBCUTANEOUS INJECTION MODEL; ENDOCRINE-DISRUPTING CHEMICALS; IN-HOUSE DUST; DI-N-BUTYL; DI-(2-ETHYLHEXYL) PHTHALATE; BALB/C MICE; DI(2-ETHYLHEXYL) PHTHALATE; AIRWAY INFLAMMATION; YOUNG-CHILDREN; MONO-2-ETHYLHEXYL PHTHALATE	P>During the last decades more than 100 000 new chemicals have been introduced to the environment. Many of these new chemicals and many common consumer products that include these have been shown to be toxic in animal studies and an increasing body of evidence suggests that they are also impacting human health. Among the suspect chemicals, the endocrine disrupting chemicals (EDCs) are of particular concern. One such chemical group is the phthalates, used in soft poly vinyl chloride (PVC) material and in a huge number of consumer products. During the same period of time that the prevalence of these modern chemicals has increased, there has been a remarkable increase in several chronic illnesses, including asthma and allergy in children. In this article we outline the scientific knowledge on phthalate exposure for asthma and airway diseases in children by examining epidemiological and experimental peer review data for potential explanatory mechanisms. Epidemiological data point to a possible correlation between phthalate exposure and asthma and airway diseases in children. Experimental studies present support for an adjuvant effect on basic mechanisms in allergic sensitization by several phthalates. Despite variations in the experimental design and reported result in the individual studies, a majority of published reports have identified adjuvant effects on Th2 differentiation, production of Th2 cytokines and enhanced levels of Th2 promoted immunoglobulins (mainly IgG1 but also IgE) in mice. A limited amount of data do also suggest phthalate-induced enhancement of mast cell degranulation and eosinophilic infiltration which are important parts in the early inflammation phase. Thus, some of the early key mechanisms in the pathology of allergic asthma could possibly be targeted by phthalate exposure. But the important questions of clinical relevance of real life exposure and identification of molecular targets that can explain interactions largely remain to be answered.	64	96	2010	13	10.1111/j.1365-2605.2009.01023.x	Endocrinology & Metabolism
Antibiotic Use in Children Is Associated With Increased Risk of Asthma. BACKGROUND. Antibiotic exposure in early childhood is a possible contributor to the increasing asthma prevalence in industrialized countries. Although a number of published studies have tested this hypothesis, the results have been conflicting. OBJECTIVE. To explore the association between antibiotic exposure before 1 year of age and development of childhood asthma. METHODS. Using administrative data, birth cohorts from 1997 to 2003 were evaluated (N = 251 817). Antibiotic exposure was determined for the first year of life. After the first 24 months of life, the incidence of asthma was determined in both those exposed and not exposed to antibiotics in the first 12 months of life. Cox proportional hazards models were used to adjust for potential confounders and determine the hazard ratios associated with antibiotic exposure for the development of asthma. RESULTS. Antibiotic exposure in the first year of life was associated with a small risk of developing asthma in early childhood after adjusting for gender, socioeconomic status at birth, urban or rural address at birth, birth weight, gestational age, delivery method, frequency of physician visits, hospital visit involving surgery, visits to an allergist, respirologist, or immunologist, congenital anomalies, and presence of otitis media, acute, or chronic bronchitis, and upper and lower respiratory tract infections during the first year of life. As the number of courses of antibiotics increased, this was associated with increased asthma risk, with the highest risk being in children who received > 4 courses. All antibiotics were associated with an increased risk of developing asthma, with the exception of sulfonamides. CONCLUSIONS. This study provides evidence that the use of antibiotics in the first year of life is associated with a small risk of developing asthma, and this risk increases with the number of courses of antibiotics prescribed. Pediatrics 2009;123:1003-1010. asthma| antibiotics| epidemiology| children| pediatrics|early-childhood| allergic disease| birth cohort| 1st year| life| infections| causation| committee| rhinitis| exposure.	MAR-2009	asthma| antibiotics| epidemiology| children| pediatrics|early-childhood| allergic disease| birth cohort| 1st year| life| infections| causation| committee| rhinitis| exposure	Marra, F; Marra, CA; Richardson, K; Lynd, LD; Kozyrskyj, A; Patrick, DM; Bowie, WR; FitzGerald, JM	Antibiotic Use in Children Is Associated With Increased Risk of Asthma		PEDIATRICS	asthma; antibiotics; epidemiology; children; pediatrics	EARLY-CHILDHOOD; ALLERGIC DISEASE; BIRTH COHORT; 1ST YEAR; LIFE; INFECTIONS; CAUSATION; COMMITTEE; RHINITIS; EXPOSURE	BACKGROUND. Antibiotic exposure in early childhood is a possible contributor to the increasing asthma prevalence in industrialized countries. Although a number of published studies have tested this hypothesis, the results have been conflicting. OBJECTIVE. To explore the association between antibiotic exposure before 1 year of age and development of childhood asthma. METHODS. Using administrative data, birth cohorts from 1997 to 2003 were evaluated (N = 251 817). Antibiotic exposure was determined for the first year of life. After the first 24 months of life, the incidence of asthma was determined in both those exposed and not exposed to antibiotics in the first 12 months of life. Cox proportional hazards models were used to adjust for potential confounders and determine the hazard ratios associated with antibiotic exposure for the development of asthma. RESULTS. Antibiotic exposure in the first year of life was associated with a small risk of developing asthma in early childhood after adjusting for gender, socioeconomic status at birth, urban or rural address at birth, birth weight, gestational age, delivery method, frequency of physician visits, hospital visit involving surgery, visits to an allergist, respirologist, or immunologist, congenital anomalies, and presence of otitis media, acute, or chronic bronchitis, and upper and lower respiratory tract infections during the first year of life. As the number of courses of antibiotics increased, this was associated with increased asthma risk, with the highest risk being in children who received > 4 courses. All antibiotics were associated with an increased risk of developing asthma, with the exception of sulfonamides. CONCLUSIONS. This study provides evidence that the use of antibiotics in the first year of life is associated with a small risk of developing asthma, and this risk increases with the number of courses of antibiotics prescribed. Pediatrics 2009;123:1003-1010	23	96	2009	8	10.1542/peds.2008-1146	Pediatrics
The Effects of Fine Particle Components on Respiratory Hospital Admissions in Children. BACKGROUND: Epidemiologic studies have demonstrated an association between acute exposure to ambient fine particles and both mortality and morbidity. Less is known about the relative impacts of the specific chemical constituents of particulate matter < 2.5 mu m in aerodynamic diameter (PM(2.5)) on hospital admissions. OBJECTIVE: This study was designed to estimate the risks of exposure to PM(2.5) and several species on hospital admissions for respiratory diseases among children. DATA AND METHODS: We obtained data on daily counts of hospitalizations for children < 19 and < 5 years of age for total respiratory diseases and several subcategories including pneumonia, acute bronchitis, and asthma for six California counties from 2000 through 2003, as well as ambient concentrations Of PM2.5 and its constituents, including elemental carbon (EC), organic carbon (OC), and nitrates (NO(3)). We used Poisson regression to estimate risks while controlling for important covariates. RESULTS: We observed associations between several components of PM(2.5) and hospitalization for all of the respiratory outcomes examined. For example, for total respiratory admissions for children < 19 years of age, the interquartile range for a 3-day lag of PM(2.5), EC, OC, NO(3), and sulfates was associated with an excess risk of 4.1% [95% confidence interval (CI), 1.8-6.4], 5.4% (95% CI, 0.8-10-3), 3.4% (95% CI, 1.1-5-7), 3.3% (95% CI, 1.1-5.5), and 3.0% (95% CI, 0.4-5-7), respectively. We also observed associations for several metals. Additional associations with several of the species, including potassium, were observed in the cool season. CONCLUSION: Components of PM(2.5) were associated with hospitalization for several childhood respiratory diseases including pneumonia, bronchitis, and asthma. Because exposure to components (e.g., EC, OC, NO(3), and K) and their related sources, including diesel and gasoline exhaust, wood smoke, and other combustion sources, are ubiquitous in the urban environment, it likely represents an identifiable and preventable risk factor for hospitalization for children.. children| ec| hospital admissions| oc| pm(2.5)| respiratory| species|particulate air-pollution| diesel exhaust particles| 9 california counties| ambient air| source-apportionment| daily mortality| risk-assessment| case-crossover| utah valley| gas-phase.	MAR-2009	children| ec| hospital admissions| oc| pm(2.5)| respiratory| species|particulate air-pollution| diesel exhaust particles| 9 california counties| ambient air| source-apportionment| daily mortality| risk-assessment| case-crossover| utah valley| gas-phase	Ostro, B; Roth, L; Malig, B; Marty, M	The Effects of Fine Particle Components on Respiratory Hospital Admissions in Children		ENVIRONMENTAL HEALTH PERSPECTIVES	children; EC; hospital admissions; OC; PM(2.5); respiratory; species	PARTICULATE AIR-POLLUTION; DIESEL EXHAUST PARTICLES; 9 CALIFORNIA COUNTIES; AMBIENT AIR; SOURCE-APPORTIONMENT; DAILY MORTALITY; RISK-ASSESSMENT; CASE-CROSSOVER; UTAH VALLEY; GAS-PHASE	BACKGROUND: Epidemiologic studies have demonstrated an association between acute exposure to ambient fine particles and both mortality and morbidity. Less is known about the relative impacts of the specific chemical constituents of particulate matter < 2.5 mu m in aerodynamic diameter (PM(2.5)) on hospital admissions. OBJECTIVE: This study was designed to estimate the risks of exposure to PM(2.5) and several species on hospital admissions for respiratory diseases among children. DATA AND METHODS: We obtained data on daily counts of hospitalizations for children < 19 and < 5 years of age for total respiratory diseases and several subcategories including pneumonia, acute bronchitis, and asthma for six California counties from 2000 through 2003, as well as ambient concentrations Of PM2.5 and its constituents, including elemental carbon (EC), organic carbon (OC), and nitrates (NO(3)). We used Poisson regression to estimate risks while controlling for important covariates. RESULTS: We observed associations between several components of PM(2.5) and hospitalization for all of the respiratory outcomes examined. For example, for total respiratory admissions for children < 19 years of age, the interquartile range for a 3-day lag of PM(2.5), EC, OC, NO(3), and sulfates was associated with an excess risk of 4.1% [95% confidence interval (CI), 1.8-6.4], 5.4% (95% CI, 0.8-10-3), 3.4% (95% CI, 1.1-5-7), 3.3% (95% CI, 1.1-5.5), and 3.0% (95% CI, 0.4-5-7), respectively. We also observed associations for several metals. Additional associations with several of the species, including potassium, were observed in the cool season. CONCLUSION: Components of PM(2.5) were associated with hospitalization for several childhood respiratory diseases including pneumonia, bronchitis, and asthma. Because exposure to components (e.g., EC, OC, NO(3), and K) and their related sources, including diesel and gasoline exhaust, wood smoke, and other combustion sources, are ubiquitous in the urban environment, it likely represents an identifiable and preventable risk factor for hospitalization for children.	59	96	2009	6	10.1289/ehp.11848	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Social Determinants: Taking the Social Context of Asthma Seriously. Although asthma has emerged as a major contributor to disease and disability among US children, the burden of this disease is unevenly distributed within the population. This article provides a brief overview of social-status variables that predict variations in asthma risks and social exposures, such as stress and violence, that are emerging as important risk factors. The central focus of the article is on the distal social variables that have given rise to unhealthy residential environments in which the risk factors for asthma and other diseases are clustered. Effective initiatives for the prevention and treatment of childhood asthma need to address these nonmedical determinants of the prevalence of asthma. Pediatrics 2009; 123:S174-S184. childhood asthma prevalence| low-income population| poverty| race| risk factors|racial residential segregation| air-pollution| collective efficacy| lung-function| urban asthma| atherosclerosis risk| socioeconomic-status| childhood asthma| spatial dynamics| childrens health.	MAR-2009	childhood asthma prevalence| low-income population| poverty| race| risk factors|racial residential segregation| air-pollution| collective efficacy| lung-function| urban asthma| atherosclerosis risk| socioeconomic-status| childhood asthma| spatial dynamics| childrens health	Williams, DR; Sternthal, M; Wright, RJ	Social Determinants: Taking the Social Context of Asthma Seriously		PEDIATRICS	childhood asthma prevalence; low-income population; poverty; race; risk factors	RACIAL RESIDENTIAL SEGREGATION; AIR-POLLUTION; COLLECTIVE EFFICACY; LUNG-FUNCTION; URBAN ASTHMA; ATHEROSCLEROSIS RISK; SOCIOECONOMIC-STATUS; CHILDHOOD ASTHMA; SPATIAL DYNAMICS; CHILDRENS HEALTH	Although asthma has emerged as a major contributor to disease and disability among US children, the burden of this disease is unevenly distributed within the population. This article provides a brief overview of social-status variables that predict variations in asthma risks and social exposures, such as stress and violence, that are emerging as important risk factors. The central focus of the article is on the distal social variables that have given rise to unhealthy residential environments in which the risk factors for asthma and other diseases are clustered. Effective initiatives for the prevention and treatment of childhood asthma need to address these nonmedical determinants of the prevalence of asthma. Pediatrics 2009; 123:S174-S184	94	96	2009	11	10.1542/peds.2008-2233H	Pediatrics
Health effects due to endotoxin inhalation (review). Endotoxins are ubiquitous in the environment and represent important components of bioaerosols. High exposure occurs in rural environment and at several workplaces (e.g. waste collecting, textile industry etc.). Adverse effects on human health induced by inhalation of endotoxin are described in several studies. Up to now the endotoxin levels are mainly measured using the Limulus amoebocyte-lysate (LAL) assay. This assay is well established, but for a suitable characterization of bioaerosols more parameters are necessary. Additional information, e.g. concerning the pyrogenic activity of organic dust samples may be delivered by whole blood assay. Whereas on the one hand protection measures at workplaces are demanded to avoid lung function impairment due to endotoxin exposure, on the other hand a protective effect of exposure to microbial agents like endotoxins with regard to allergy development has been observed. On the cellular level toll-like receptor 4 (TLR4) and IL-1 receptor as well as surface molecules like CD14 have been shown to play a pivotal role in the endotoxin activation cascade. In this review we summarize the mechanism of endotoxin recognition and its manifold effects on human health.. endotoxin| health effects| lal-test| whole blood assay-allergy|dose-response relationships| organic dust| lung-function| follow-up| occupational-exposure| airborne endotoxin| cytokine responses| lps inhalation| cotton dust| in-vivo.	APR-2008	endotoxin| health effects| lal-test| whole blood assay-allergy|dose-response relationships| organic dust| lung-function| follow-up| occupational-exposure| airborne endotoxin| cytokine responses| lps inhalation| cotton dust| in-vivo	Liebers, V; Raulf-Heimsoth, M; Bruning, T	Health effects due to endotoxin inhalation (review)		ARCHIVES OF TOXICOLOGY	endotoxin; health effects; LAL-test; whole blood assay-allergy	DOSE-RESPONSE RELATIONSHIPS; ORGANIC DUST; LUNG-FUNCTION; FOLLOW-UP; OCCUPATIONAL-EXPOSURE; AIRBORNE ENDOTOXIN; CYTOKINE RESPONSES; LPS INHALATION; COTTON DUST; IN-VIVO	Endotoxins are ubiquitous in the environment and represent important components of bioaerosols. High exposure occurs in rural environment and at several workplaces (e.g. waste collecting, textile industry etc.). Adverse effects on human health induced by inhalation of endotoxin are described in several studies. Up to now the endotoxin levels are mainly measured using the Limulus amoebocyte-lysate (LAL) assay. This assay is well established, but for a suitable characterization of bioaerosols more parameters are necessary. Additional information, e.g. concerning the pyrogenic activity of organic dust samples may be delivered by whole blood assay. Whereas on the one hand protection measures at workplaces are demanded to avoid lung function impairment due to endotoxin exposure, on the other hand a protective effect of exposure to microbial agents like endotoxins with regard to allergy development has been observed. On the cellular level toll-like receptor 4 (TLR4) and IL-1 receptor as well as surface molecules like CD14 have been shown to play a pivotal role in the endotoxin activation cascade. In this review we summarize the mechanism of endotoxin recognition and its manifold effects on human health.	68	96	2008	8	10.1007/s00204-008-0290-1	Toxicology
Intra-urban variability of air pollution in Windsor, Ontario - Measurement and modeling for human exposure assessment. There are acknowledged difficulties in epidemiological studies to accurately assign exposure to air pollution for large populations, and large, long-term cohort studies have typically relied upon data from central monitoring stations. This approach has generally been adequate when populations span large areas or diverse cities. However, when the effects of intra-urban differences in exposure are being studied, the use of these existing central sites are likely to be inadequate for representing spatial variability that exists within an urban area. As part of the Border Air Quality Strategy (BAQS), an international agreement between the governments of Canada and the United States, a number of air health effects studies are being undertaken by Health Canada and the US EPA. Health Canada's research largely focuses on the chronic exposure of elementary school children to air pollution. The exposure characterization for this population to a variety of air pollutants has been assessed using land-use regression (LUR) models. This approach has been applied in several cities to nitrogen dioxide (NO2), as an assumed traffic exposure marker. However, the models have largely been developed from limited periods of saturation monitoring data and often only represent one or two seasons. Two key questions from these previous efforts, which are examined in this paper, are: If NO2 is a traffic marker, what other pollutants, potentially traffic related, might it actually represent? How well is the within city spatial variability of NO2, and other traffic-related pollutants, characterized by a single saturation monitoring campaign. Input data for the models developed in this paper were obtained across a network of 54 monitoring sites situated across Windsor, Ontario. The pollutants studied were NO2, sulfur dioxide (SO2) and volatile organic compounds, which were measured in all four seasons by deploying passive samplers for 2-week periods. Correlations among these pollutants were calculated to assess what other pollutants NO2 might represent, and correlations across seasons for a given pollutant were determined to assess how much the within-city spatial pattern varies with time. LUR models were then developed for NO2, SO2, benzene, and toluene. A multiple regression model including proximity to the Ambassador Bridge (the main Canada-US border crossing point), and proximity to highways and major roads, predicted NO2 concentrations with an R-2 = 0.77. The SO2 model predictors included distance to the Ambassador Bridge, dwelling density within 1500 in, and Detroit-based SO2 emitters within 3000 in resulting in a model with an R-2 = 0.69. Benzene and toluene LUR models included traffic predictors as well as point source emitters resulting in R-2 = 0.73 and 0.46, respectively. Between season pollutant correlations were all significant although actual concentrations for each site varied by season. This suggests that if one season were to be selected to represent the annual concentrations for a specific site this may lead to a potential under or overestimation in exposure, which could be significant for health research. All pollutants had strong inter-pollutant correlations suggesting that NO2 could represent SO2, benzene, and toluene. Crown Copyright (c) 2007 Published by Elsevier Inc. All rights reserved.. air pollution| land-use regression (lur)| geographic information systems (gis)| road traffic| exposure assessment|ambient nitrogen-dioxide| childhood asthma| spatial variability| mortality| association| children| indicators| symptoms| cities| sulfur.	JAN-2008	air pollution| land-use regression (lur)| geographic information systems (gis)| road traffic| exposure assessment|ambient nitrogen-dioxide| childhood asthma| spatial variability| mortality| association| children| indicators| symptoms| cities| sulfur	Wheeler, AJ; Smith-Doiron, M; Xu, X; Gilbert, NL; Brook, JR	Intra-urban variability of air pollution in Windsor, Ontario - Measurement and modeling for human exposure assessment		ENVIRONMENTAL RESEARCH	air pollution; land-use regression (LUR); geographic information systems (GIS); road traffic; exposure assessment	AMBIENT NITROGEN-DIOXIDE; CHILDHOOD ASTHMA; SPATIAL VARIABILITY; MORTALITY; ASSOCIATION; CHILDREN; INDICATORS; SYMPTOMS; CITIES; SULFUR	There are acknowledged difficulties in epidemiological studies to accurately assign exposure to air pollution for large populations, and large, long-term cohort studies have typically relied upon data from central monitoring stations. This approach has generally been adequate when populations span large areas or diverse cities. However, when the effects of intra-urban differences in exposure are being studied, the use of these existing central sites are likely to be inadequate for representing spatial variability that exists within an urban area. As part of the Border Air Quality Strategy (BAQS), an international agreement between the governments of Canada and the United States, a number of air health effects studies are being undertaken by Health Canada and the US EPA. Health Canada's research largely focuses on the chronic exposure of elementary school children to air pollution. The exposure characterization for this population to a variety of air pollutants has been assessed using land-use regression (LUR) models. This approach has been applied in several cities to nitrogen dioxide (NO2), as an assumed traffic exposure marker. However, the models have largely been developed from limited periods of saturation monitoring data and often only represent one or two seasons. Two key questions from these previous efforts, which are examined in this paper, are: If NO2 is a traffic marker, what other pollutants, potentially traffic related, might it actually represent? How well is the within city spatial variability of NO2, and other traffic-related pollutants, characterized by a single saturation monitoring campaign. Input data for the models developed in this paper were obtained across a network of 54 monitoring sites situated across Windsor, Ontario. The pollutants studied were NO2, sulfur dioxide (SO2) and volatile organic compounds, which were measured in all four seasons by deploying passive samplers for 2-week periods. Correlations among these pollutants were calculated to assess what other pollutants NO2 might represent, and correlations across seasons for a given pollutant were determined to assess how much the within-city spatial pattern varies with time. LUR models were then developed for NO2, SO2, benzene, and toluene. A multiple regression model including proximity to the Ambassador Bridge (the main Canada-US border crossing point), and proximity to highways and major roads, predicted NO2 concentrations with an R-2 = 0.77. The SO2 model predictors included distance to the Ambassador Bridge, dwelling density within 1500 in, and Detroit-based SO2 emitters within 3000 in resulting in a model with an R-2 = 0.69. Benzene and toluene LUR models included traffic predictors as well as point source emitters resulting in R-2 = 0.73 and 0.46, respectively. Between season pollutant correlations were all significant although actual concentrations for each site varied by season. This suggests that if one season were to be selected to represent the annual concentrations for a specific site this may lead to a potential under or overestimation in exposure, which could be significant for health research. All pollutants had strong inter-pollutant correlations suggesting that NO2 could represent SO2, benzene, and toluene. Crown Copyright (c) 2007 Published by Elsevier Inc. All rights reserved.	23	96	2008	10	10.1016/j.envres.2007.09.004	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
A review of the toxicity of Melaleuca alternifolia (tea tree) oil. The essential oil of Melaleuca alternifolia, also known as tea tree or melaleuca oil, is widely available and has been investigated as an alternative antimicrobial, anti-inflammatory and anti-cancer agent. While these properties are increasingly well characterised, relatively limited data are available on the safety and toxicity of the oil. Anecdotal evidence from almost 80 years of use suggests that the topical use of the oil is relatively safe, and that adverse events are minor, self-limiting and occasional. Published data indicate that TTO is toxic if ingested in higher doses and can also cause skin irritation at higher concentrations. Allergic reactions to TTO occur in predisposed individuals and may be due to the various oxidation products that are formed by exposure of the oil to light and/or air. Adverse reactions may be minimised by avoiding ingestion, applying only diluted oil topically and using oil that has been stored correctly. Data from individual components suggest that TTO has the potential to be developmentally toxic if ingested at higher doses, however, TTO and its components are not genotoxic. The limited ecotoxicity data available indicate that TTO is toxic to some insect species but more studies are required. (c) 2005 Elsevier Ltd. All rights reserved.. essential oil| terpene| allergy| ecotoxicity|plant essential oils| allergic contact-dermatitis| beta-myrcene| in-vitro| insecticidal activity| rainbow-trout| salmonella/microsome assay| fumigant toxicity| alpha-terpinene| human monocytes.	MAY-2006	essential oil| terpene| allergy| ecotoxicity|plant essential oils| allergic contact-dermatitis| beta-myrcene| in-vitro| insecticidal activity| rainbow-trout| salmonella/microsome assay| fumigant toxicity| alpha-terpinene| human monocytes	Hammer, KA; Carson, CF; Riley, TV; Nielsen, JB	A review of the toxicity of Melaleuca alternifolia (tea tree) oil		FOOD AND CHEMICAL TOXICOLOGY	essential oil; terpene; allergy; ecotoxicity	PLANT ESSENTIAL OILS; ALLERGIC CONTACT-DERMATITIS; BETA-MYRCENE; IN-VITRO; INSECTICIDAL ACTIVITY; RAINBOW-TROUT; SALMONELLA/MICROSOME ASSAY; FUMIGANT TOXICITY; ALPHA-TERPINENE; HUMAN MONOCYTES	The essential oil of Melaleuca alternifolia, also known as tea tree or melaleuca oil, is widely available and has been investigated as an alternative antimicrobial, anti-inflammatory and anti-cancer agent. While these properties are increasingly well characterised, relatively limited data are available on the safety and toxicity of the oil. Anecdotal evidence from almost 80 years of use suggests that the topical use of the oil is relatively safe, and that adverse events are minor, self-limiting and occasional. Published data indicate that TTO is toxic if ingested in higher doses and can also cause skin irritation at higher concentrations. Allergic reactions to TTO occur in predisposed individuals and may be due to the various oxidation products that are formed by exposure of the oil to light and/or air. Adverse reactions may be minimised by avoiding ingestion, applying only diluted oil topically and using oil that has been stored correctly. Data from individual components suggest that TTO has the potential to be developmentally toxic if ingested at higher doses, however, TTO and its components are not genotoxic. The limited ecotoxicity data available indicate that TTO is toxic to some insect species but more studies are required. (c) 2005 Elsevier Ltd. All rights reserved.	88	96	2006	10	10.1016/j.fct.2005.09.001	Food Science & Technology; Toxicology
Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis. Introduction Our objectives were to determine the causes of acute respiratory failure (ARF) in elderly patients and to assess the accuracy of the initial diagnosis by the emergency physician, and that of the prognosis. Method In this prospective observational study, patients were included if they were admitted to our emergency department, aged 65 years or more with dyspnea, and fulfilled at least one of the following criteria of ARF: respiratory rate at least 25 minute(-1); arterial partial pressure of oxygen (PaO2) 70 mmHg or less, or peripheral oxygen saturation 92% or less in breathing room air; arterial partial pressure of CO2 (PaCO2) >= 45 mmHg, with pH <= 7.35. The final diagnoses were determined by an expert panel from the completed medical chart. Results A total of 514 patients ( aged ( mean +/- standard deviation) 80 +/- 9 years) were included. The main causes of ARF were cardiogenic pulmonary edema (43%), community-acquired pneumonia (35%), acute exacerbation of chronic respiratory disease (32%), pulmonary embolism (18%), and acute asthma (3%); 47% had more than two diagnoses. Inhospital mortality was 16%. A missed diagnosis in the emergency department was noted in 101 (20%) patients. The accuracy of the diagnosis of the emergency physician ranged from 0.76 for cardiogenic pulmonary edema to 0.96 for asthma. An inappropriate treatment occurred in 162 (32%) patients, and lead to a higher mortality (25% versus 11%; p < 0.001). In a multivariate analysis, inappropriate initial treatment ( odds ratio 2.83, p < 0.002), hypercapnia > 45 mmHg ( odds ratio 2.79, p < 0.004), clearance of creatinine < 50 ml minute(-1) ( odds ratio 2.37, p < 0.013), elevated NT-pro-B-type natriuretic peptide or B-type natriuretic peptide ( odds ratio 2.06, p < 0.046), and clinical signs of acute ventilatory failure ( odds ratio 1.98, p < 0.047) were predictive of death. Conclusion Inappropriate initial treatment in the emergency room was associated with increased mortality in elderly patients with ARF.. congestive-heart-failure| community-acquired pneumonia| cardiogenic pulmonary-edema| quality-of-care| natriuretic peptide| survey program| acute dyspnea| management| patient| guidelines.	2006	congestive-heart-failure| community-acquired pneumonia| cardiogenic pulmonary-edema| quality-of-care| natriuretic peptide| survey program| acute dyspnea| management| patient| guidelines	Ray, P; Birolleau, S; Lefort, Y; Becquemin, MH; Beigelman, C; Isnard, R; Teixeira, A; Arthaud, M; Riou, B; Boddaert, J	Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis		CRITICAL CARE		CONGESTIVE-HEART-FAILURE; COMMUNITY-ACQUIRED PNEUMONIA; CARDIOGENIC PULMONARY-EDEMA; QUALITY-OF-CARE; NATRIURETIC PEPTIDE; SURVEY PROGRAM; ACUTE DYSPNEA; MANAGEMENT; PATIENT; GUIDELINES	Introduction Our objectives were to determine the causes of acute respiratory failure (ARF) in elderly patients and to assess the accuracy of the initial diagnosis by the emergency physician, and that of the prognosis. Method In this prospective observational study, patients were included if they were admitted to our emergency department, aged 65 years or more with dyspnea, and fulfilled at least one of the following criteria of ARF: respiratory rate at least 25 minute(-1); arterial partial pressure of oxygen (PaO2) 70 mmHg or less, or peripheral oxygen saturation 92% or less in breathing room air; arterial partial pressure of CO2 (PaCO2) >= 45 mmHg, with pH <= 7.35. The final diagnoses were determined by an expert panel from the completed medical chart. Results A total of 514 patients ( aged ( mean +/- standard deviation) 80 +/- 9 years) were included. The main causes of ARF were cardiogenic pulmonary edema (43%), community-acquired pneumonia (35%), acute exacerbation of chronic respiratory disease (32%), pulmonary embolism (18%), and acute asthma (3%); 47% had more than two diagnoses. Inhospital mortality was 16%. A missed diagnosis in the emergency department was noted in 101 (20%) patients. The accuracy of the diagnosis of the emergency physician ranged from 0.76 for cardiogenic pulmonary edema to 0.96 for asthma. An inappropriate treatment occurred in 162 (32%) patients, and lead to a higher mortality (25% versus 11%; p < 0.001). In a multivariate analysis, inappropriate initial treatment ( odds ratio 2.83, p < 0.002), hypercapnia > 45 mmHg ( odds ratio 2.79, p < 0.004), clearance of creatinine < 50 ml minute(-1) ( odds ratio 2.37, p < 0.013), elevated NT-pro-B-type natriuretic peptide or B-type natriuretic peptide ( odds ratio 2.06, p < 0.046), and clinical signs of acute ventilatory failure ( odds ratio 1.98, p < 0.047) were predictive of death. Conclusion Inappropriate initial treatment in the emergency room was associated with increased mortality in elderly patients with ARF.	34	96	2006	12	10.1186/cc4926	General & Internal Medicine
Structural changes in the airways in asthma: observations and consequences. Structural changes reported in the airways of asthmatics include epithelial fragility, goblet cell hyperplasia, enlarged submucosal mucus glands, angiogenesis, increased matrix deposition in the airway wall, increased airway smooth muscle mass, wall thickening and abnormalities in elastin. Genetic influences, as well as fetal and early life exposures, may contribute to structural changes such as subepithelial fibrosis from an early age. Other structural alterations are related to duration of disease and/or long-term uncontrolled inflammation. The increase in smooth muscle mass in both large and small airways probably occurs via multiple mechanisms, and there are probably changes in the phenotype of smooth muscle cells, some showing enhanced synthetic capacity, others enhanced proliferation or contractility. Fixed airflow limitation is probably due to remodelling, whereas the importance of structural changes to the phenomenon of airways hyperresponsiveness may be dependent on the specific clinical phenotype of asthma evaluated. Reduced compliance of the airway wall secondary to enhanced matrix deposition may protect against airway narrowing. Conversely, in severe asthma, disruption of alveolar attachments and adventitial thickening may augment airway narrowing. The encroachment upon luminal area by submucosal thickening may be disadvantageous by increasing the risk of airway closure in the presence of the intraluminal cellular and mucus exudate associated with asthma exacerbations. Structural changes may increase airway narrowing by alteration of smooth muscle dynamics through limitation of the ability of the smooth muscle to periodically lengthen.. airway smooth muscle| asthma| corticosteroid| fibrosis| lung function| matrix| remodelling|obstructive pulmonary-disease| air-flow limitation| reticular basement-membrane| smooth-muscle-cells| long-term treatment| 30-year follow-up| lung-function| fatal asthma| risk-factors| bronchial-asthma.	JUN-2005	airway smooth muscle| asthma| corticosteroid| fibrosis| lung function| matrix| remodelling|obstructive pulmonary-disease| air-flow limitation| reticular basement-membrane| smooth-muscle-cells| long-term treatment| 30-year follow-up| lung-function| fatal asthma| risk-factors| bronchial-asthma	Bai, TR; Knight, DA	Structural changes in the airways in asthma: observations and consequences		CLINICAL SCIENCE	airway smooth muscle; asthma; corticosteroid; fibrosis; lung function; matrix; remodelling	OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW LIMITATION; RETICULAR BASEMENT-MEMBRANE; SMOOTH-MUSCLE-CELLS; LONG-TERM TREATMENT; 30-YEAR FOLLOW-UP; LUNG-FUNCTION; FATAL ASTHMA; RISK-FACTORS; BRONCHIAL-ASTHMA	Structural changes reported in the airways of asthmatics include epithelial fragility, goblet cell hyperplasia, enlarged submucosal mucus glands, angiogenesis, increased matrix deposition in the airway wall, increased airway smooth muscle mass, wall thickening and abnormalities in elastin. Genetic influences, as well as fetal and early life exposures, may contribute to structural changes such as subepithelial fibrosis from an early age. Other structural alterations are related to duration of disease and/or long-term uncontrolled inflammation. The increase in smooth muscle mass in both large and small airways probably occurs via multiple mechanisms, and there are probably changes in the phenotype of smooth muscle cells, some showing enhanced synthetic capacity, others enhanced proliferation or contractility. Fixed airflow limitation is probably due to remodelling, whereas the importance of structural changes to the phenomenon of airways hyperresponsiveness may be dependent on the specific clinical phenotype of asthma evaluated. Reduced compliance of the airway wall secondary to enhanced matrix deposition may protect against airway narrowing. Conversely, in severe asthma, disruption of alveolar attachments and adventitial thickening may augment airway narrowing. The encroachment upon luminal area by submucosal thickening may be disadvantageous by increasing the risk of airway closure in the presence of the intraluminal cellular and mucus exudate associated with asthma exacerbations. Structural changes may increase airway narrowing by alteration of smooth muscle dynamics through limitation of the ability of the smooth muscle to periodically lengthen.	155	96	2005	15		Research & Experimental Medicine
Low socioeconomic status as a risk factor for asthma, rhinitis and sensitization at 4 years in a birth cohort. Background The relation between socioeconomic status and allergic diseases in childhood is controversial. Some studies have proposed childhood asthma to be more common in families with low socioeconomic status, while sensitization to airborne allergens seems to be more frequent in individuals with higher socioeconomic status in childhood. Objective To assess the relation between socioeconomic status and asthma, rhinitis and sensitization in an unselected prospective birth cohort. Methods Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors, socioeconomic status (parental occupation), and symptoms of allergic disease at birth, 1, 2 and 4 years of age. Blood samples taken at 4 years from 2614 children were analysed for specific IgE to common airborne and food allergens. Odds ratios (OR) and 95% confidence intervals (CI) for various outcomes in relation to socioeconomic status were estimated with a multiple logistic regression model, adjusting for potential confounders such as heredity for allergic diseases, maternal smoking, short duration of breastfeeding and house construction. Results There was a decreasing risk of asthma and rhinitis with increasing socioeconomic status. The OR for asthma was 0.33 (95% CI 0.17-0.66) and for rhinitis 0.50 (0.32-0.79) comparing the highest and the lowest socioeconomic groups, with a tendency to stronger effects in those with heredity for allergic disease. The risk of sensitization to food allergens also decreased with increasing socioeconomic status; OR 0.65 (0.41-1.02) in the highest socioeconomic group (P-trend=0.03), which was not clearly seen for airborne allergens. Conclusion Asthma, rhinitis and sensitization is more common in lower than in higher socioeconomic groups after adjustment for traditional risk factors. This may be related to additional uncontrolled differences in life style and environmental exposures between the groups, and calls for further studies.. allergy and immunology| asthma| child| primary prevention| rhinitis| socioeconomy|childhood asthma| allergic sensitization| bronchial-asthma| children| bamse| severity| stress| adults| atopy.	MAY-2005	allergy and immunology| asthma| child| primary prevention| rhinitis| socioeconomy|childhood asthma| allergic sensitization| bronchial-asthma| children| bamse| severity| stress| adults| atopy	Almqvist, C; Pershagen, G; Wickman, M	Low socioeconomic status as a risk factor for asthma, rhinitis and sensitization at 4 years in a birth cohort		CLINICAL AND EXPERIMENTAL ALLERGY	allergy and immunology; asthma; child; primary prevention; rhinitis; socioeconomy	CHILDHOOD ASTHMA; ALLERGIC SENSITIZATION; BRONCHIAL-ASTHMA; CHILDREN; BAMSE; SEVERITY; STRESS; ADULTS; ATOPY	Background The relation between socioeconomic status and allergic diseases in childhood is controversial. Some studies have proposed childhood asthma to be more common in families with low socioeconomic status, while sensitization to airborne allergens seems to be more frequent in individuals with higher socioeconomic status in childhood. Objective To assess the relation between socioeconomic status and asthma, rhinitis and sensitization in an unselected prospective birth cohort. Methods Four thousand and eighty-nine families with children born 1994-1996 in predefined areas of Stockholm answered questionnaires on environmental factors, socioeconomic status (parental occupation), and symptoms of allergic disease at birth, 1, 2 and 4 years of age. Blood samples taken at 4 years from 2614 children were analysed for specific IgE to common airborne and food allergens. Odds ratios (OR) and 95% confidence intervals (CI) for various outcomes in relation to socioeconomic status were estimated with a multiple logistic regression model, adjusting for potential confounders such as heredity for allergic diseases, maternal smoking, short duration of breastfeeding and house construction. Results There was a decreasing risk of asthma and rhinitis with increasing socioeconomic status. The OR for asthma was 0.33 (95% CI 0.17-0.66) and for rhinitis 0.50 (0.32-0.79) comparing the highest and the lowest socioeconomic groups, with a tendency to stronger effects in those with heredity for allergic disease. The risk of sensitization to food allergens also decreased with increasing socioeconomic status; OR 0.65 (0.41-1.02) in the highest socioeconomic group (P-trend=0.03), which was not clearly seen for airborne allergens. Conclusion Asthma, rhinitis and sensitization is more common in lower than in higher socioeconomic groups after adjustment for traditional risk factors. This may be related to additional uncontrolled differences in life style and environmental exposures between the groups, and calls for further studies.	23	96	2005	7	10.1111/j.1365-2222.2005.02243.x	Allergy; Immunology
Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests. Background: Bronchial provocation tests such as exercise, methacholine (MCH), and adenosine-5'-monophosphate ( AMP) challenges are used extensively in the diagnosis of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO) can be used to diagnose asthma in patients with non-specific respiratory symptoms and to compare this test with conventional provocation tests. Methods: Patients with non-specific respiratory symptoms and normal spirometric parameters were included in the study. eNO was measured and exercise, MCH and AMP challenges performed in all subjects. Patients were defined as asthmatic based on clinical follow up 24 months after testing. Results: Forty patients were considered asthmatic and 45 were not. The area under receiver operating characteristic curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939 for AMP (p = 0.033, 0.575 and 0.085 for eNO v exercise, MCH and AMP respectively). From our data, a cut off value of NO>7 ppb at a flow rate of 250 ml/s best differentiates between asthmatics and nonasthmatics (sensitivity 82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise: Delta FEV1 >= 10% (sensitivity 57.9%, specificity 100%); PC20-MCH: <= 3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: <= 150 mg/ml (sensitivity 89.5%, specificity 95.6%). Conclusions: Measurement of eNO can be used as a safe, simple and rapid test for the diagnosis of asthma and is as good as bronchial provocation tests.. obstructive pulmonary-disease| exercise| children| methacholine| air| challenges| recommendations| responsiveness| eosinophils| adenosine.	MAY-2005	obstructive pulmonary-disease| exercise| children| methacholine| air| challenges| recommendations| responsiveness| eosinophils| adenosine	Berkman, N; Avital, A; Breuer, R; Bardach, E; Springer, C; Godfrey, S	Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests		THORAX		OBSTRUCTIVE PULMONARY-DISEASE; EXERCISE; CHILDREN; METHACHOLINE; AIR; CHALLENGES; RECOMMENDATIONS; RESPONSIVENESS; EOSINOPHILS; ADENOSINE	Background: Bronchial provocation tests such as exercise, methacholine (MCH), and adenosine-5'-monophosphate ( AMP) challenges are used extensively in the diagnosis of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO) can be used to diagnose asthma in patients with non-specific respiratory symptoms and to compare this test with conventional provocation tests. Methods: Patients with non-specific respiratory symptoms and normal spirometric parameters were included in the study. eNO was measured and exercise, MCH and AMP challenges performed in all subjects. Patients were defined as asthmatic based on clinical follow up 24 months after testing. Results: Forty patients were considered asthmatic and 45 were not. The area under receiver operating characteristic curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939 for AMP (p = 0.033, 0.575 and 0.085 for eNO v exercise, MCH and AMP respectively). From our data, a cut off value of NO>7 ppb at a flow rate of 250 ml/s best differentiates between asthmatics and nonasthmatics (sensitivity 82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise: Delta FEV1 >= 10% (sensitivity 57.9%, specificity 100%); PC20-MCH: <= 3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: <= 150 mg/ml (sensitivity 89.5%, specificity 95.6%). Conclusions: Measurement of eNO can be used as a safe, simple and rapid test for the diagnosis of asthma and is as good as bronchial provocation tests.	31	96	2005	6	10.1136/thx.2004.031104	Respiratory System
Impact of sublingual immunotherapy on specific antibody levels in asthmatic children allergic to house dust mites. Objective: To evaluate the clinical outcome and changes in allergen-specific antibodies during sublingual immunotherapy ( SLIT) in house dust mite (HDM)-allergic asthma patients and to compare levels of allergen-specific antibodies in HDM-allergic patients before and after treatment with that of healthy controls. Method: Thirty-one asthma patients allergic to HDM were studied. Patients in groups I ( n = 17) and II ( n = 14) received SLIT with a standardized Dermatophagoides pteronyssinus plus Dermatophagoides farinae 50/50 extract for 6 and 12 months, respectively. A group of healthy children ( n = 8) were enrolled as controls. Patients in both groups were evaluated at the start and at the end of treatment according to daily symptom and medication scores, lung function and skin prick tests, PC20, blood eosinophil count, and Der-p-1-specific IgE, IgA, IgG1 and IgG4 levels. Results: Drug consumption decreased significantly in both groups. Furthermore, PC20 and forced expiratory flow between 25 and 75% of vital capacity of patients in group II improved significantly. Although specific IgA, IgG1 and IgG4 levels did not change throughout the treatment period, total eosinophil count and specific IgE decreased significantly in both groups. According to baseline measurements, specific IgA levels of patients in groups I and II were significantly lower than that of controls. This difference disappeared at the end of the treatment period in both groups. Conclusion: SLIT seems to be effective in ameliorating clinical symptoms, drug consumption and bronchial hyperreactivity, and results in downregulation of Der-p-1-specific IgE production. Furthermore, at the end of SLIT, specific IgA levels, which were decreased compared to healthy controls initially, did no longer differ between patients and controls. Copyright (C) 2005 S. Karger AG, Basel.. asthma| house dust mites| specific iga| sublingual immunotherapy|placebo-controlled evaluation| double-blind| swallow immunotherapy| induced rhinitis| oral tolerance| pollen extract| efficacy| rhinoconjunctivitis| trial| slit.	2005	asthma| house dust mites| specific iga| sublingual immunotherapy|placebo-controlled evaluation| double-blind| swallow immunotherapy| induced rhinitis| oral tolerance| pollen extract| efficacy| rhinoconjunctivitis| trial| slit	Bahceciler, NN; Arikan, C; Taylor, A; Akdis, M; Blaser, K; Barlan, IB; Akdis, CA	Impact of sublingual immunotherapy on specific antibody levels in asthmatic children allergic to house dust mites		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	asthma; house dust mites; specific IgA; sublingual immunotherapy	PLACEBO-CONTROLLED EVALUATION; DOUBLE-BLIND; SWALLOW IMMUNOTHERAPY; INDUCED RHINITIS; ORAL TOLERANCE; POLLEN EXTRACT; EFFICACY; RHINOCONJUNCTIVITIS; TRIAL; SLIT	Objective: To evaluate the clinical outcome and changes in allergen-specific antibodies during sublingual immunotherapy ( SLIT) in house dust mite (HDM)-allergic asthma patients and to compare levels of allergen-specific antibodies in HDM-allergic patients before and after treatment with that of healthy controls. Method: Thirty-one asthma patients allergic to HDM were studied. Patients in groups I ( n = 17) and II ( n = 14) received SLIT with a standardized Dermatophagoides pteronyssinus plus Dermatophagoides farinae 50/50 extract for 6 and 12 months, respectively. A group of healthy children ( n = 8) were enrolled as controls. Patients in both groups were evaluated at the start and at the end of treatment according to daily symptom and medication scores, lung function and skin prick tests, PC20, blood eosinophil count, and Der-p-1-specific IgE, IgA, IgG1 and IgG4 levels. Results: Drug consumption decreased significantly in both groups. Furthermore, PC20 and forced expiratory flow between 25 and 75% of vital capacity of patients in group II improved significantly. Although specific IgA, IgG1 and IgG4 levels did not change throughout the treatment period, total eosinophil count and specific IgE decreased significantly in both groups. According to baseline measurements, specific IgA levels of patients in groups I and II were significantly lower than that of controls. This difference disappeared at the end of the treatment period in both groups. Conclusion: SLIT seems to be effective in ameliorating clinical symptoms, drug consumption and bronchial hyperreactivity, and results in downregulation of Der-p-1-specific IgE production. Furthermore, at the end of SLIT, specific IgA levels, which were decreased compared to healthy controls initially, did no longer differ between patients and controls. Copyright (C) 2005 S. Karger AG, Basel.	34	96	2005	8	10.1159/000083956	Allergy; Immunology
"Dampness in buildings and health (DBH): Report from an ongoing epidemiological investigation on the association between indoor environmental factors and health effects among children in Sweden. With the aim of identifying health-relevant exposures in buildings, an epidemiological study ""Dampness in Buildings and Health"" (DBH) started in the year 2000 in Sweden. The health focus of the study is on asthma and allergic symptoms among small children and their parents. The first step in the study was an epidemiological cross-sectional questionnaire on housing and health involving 14,077 preschool children in the county of Varmland in Sweden (March-April 2000). Self-reported moisture-related problems in the building were strongly associated with asthma, allergic symptoms, and airway infections among children and adults. Other factors associated with symptoms among the children were allergic heredity, smoking in the family, male sex, urban living, short breast feeding, pet keeping, daycare attendance, non-farming life and some food habits. The second step in the study was a nested case-control study including 198 children with symptoms and 202 healthy controls. A detailed clinical examination by physicians in parallel with extensive inspections and measurements in the subjects' homes were conducted from October 2001 to April 2002. The influence of selection bias in case-control studies has been studied, and questionnaires on self-reported symptoms and building characteristics have been validated. Identified risk factors for allergic symptoms are, e.g., inspector-observed dampness, a low ventilation rate, endotoxin, Penicillium and phthalates in dust. In the third phase, a 5-year follow-up study will be carried out during 2005. The same questionnaire as used in DBH-phase 1 will be distributed to the 10,852 children/parents who responded to the first questionnaire in 2000. Finally, in a fourth phase, controlled experimental studies in climate chambers and in vitro tests regarding findings from DBH-Phase 2 are planned to be conducted during 2004-08.. asthma| allergy| home| dampness| ventilation| pets| plasticisers|scientific evidence| asthma| exposure| prevalence."	AUG-2004	asthma| allergy| home| dampness| ventilation| pets| plasticisers|scientific evidence| asthma| exposure| prevalence	Bornehag, CG; Sundell, J; Sigsgaard, T	Dampness in buildings and health (DBH): Report from an ongoing epidemiological investigation on the association between indoor environmental factors and health effects among children in Sweden		INDOOR AIR	asthma; allergy; home; dampness; ventilation; pets; plasticisers	SCIENTIFIC EVIDENCE; ASTHMA; EXPOSURE; PREVALENCE	"With the aim of identifying health-relevant exposures in buildings, an epidemiological study ""Dampness in Buildings and Health"" (DBH) started in the year 2000 in Sweden. The health focus of the study is on asthma and allergic symptoms among small children and their parents. The first step in the study was an epidemiological cross-sectional questionnaire on housing and health involving 14,077 preschool children in the county of Varmland in Sweden (March-April 2000). Self-reported moisture-related problems in the building were strongly associated with asthma, allergic symptoms, and airway infections among children and adults. Other factors associated with symptoms among the children were allergic heredity, smoking in the family, male sex, urban living, short breast feeding, pet keeping, daycare attendance, non-farming life and some food habits. The second step in the study was a nested case-control study including 198 children with symptoms and 202 healthy controls. A detailed clinical examination by physicians in parallel with extensive inspections and measurements in the subjects' homes were conducted from October 2001 to April 2002. The influence of selection bias in case-control studies has been studied, and questionnaires on self-reported symptoms and building characteristics have been validated. Identified risk factors for allergic symptoms are, e.g., inspector-observed dampness, a low ventilation rate, endotoxin, Penicillium and phthalates in dust. In the third phase, a 5-year follow-up study will be carried out during 2005. The same questionnaire as used in DBH-phase 1 will be distributed to the 10,852 children/parents who responded to the first questionnaire in 2000. Finally, in a fourth phase, controlled experimental studies in climate chambers and in vitro tests regarding findings from DBH-Phase 2 are planned to be conducted during 2004-08."	29	96	2004	8	10.1111/j.1600-0668.2004.00274.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen. Although high dose exposure to inhaled cat allergen (Fel d 1) can cause a form of tolerance (modified Th2 response), the T cell mechanism for this phenomenon has not been studied. T cell responses to Fel d 1 were characterized in both allergic (IgE(pos)) and modified Th2 (IgE(neg)IgG(pos)) responders as well as serum Ab-negative controls (IgE(neg)IgG(neg)). Fel d 1 stimulated high levels of IL-10 in PBMC cultures from all individuals, with evidence of Th2 and Th1 cytokine skewing in allergic and control subjects, respectively. Using overlapping peptides, epitopes at the N terminus of Fel d 1 chain 2 were shown to stimulate strong T cell proliferation and to preferentially induce IL-10 (peptide 2:1 (P2:1)) or IFN-gamma (P2:2) regardless of the allergic status of the donor. Injection of cat extract during conventional immunotherapy stimulated expansion of IL-10- and IFN-gamma-producing chain 2 epitope-specific T cells along with increased Fel d 1-specific serum IgG and IgG4 Ab. Six of 12 modified responders expressed the major HLA-DRB1 allele, *0701, and both P2:1 and P2:2 were predicted ligands for this allele. Cultures from DR7-positive modified responders produced the highest levels of IL-10 to P2:1 in addition to other major and minor epitopes within chains 1 and 2. In the presence of anti-IL-10 mAb, both T cell proliferation and IFN-gamma production were enhanced in a Fel d 1- and epitope-specific manner. We conclude that IL-10-producing T cells specific for chain 2 epitopes are relevant to tolerance induction, and that DR7-restricted recognition of these epitopes favors a modified Th2 response.. delayed-type hypersensitivity| late asthmatic reactions| fel-d-i| monoclonal-antibodies| positive association| sequence-analysis| dendritic cells| igg4 antibodies| major allergen| domestic cat.	MAR 1-2004	delayed-type hypersensitivity| late asthmatic reactions| fel-d-i| monoclonal-antibodies| positive association| sequence-analysis| dendritic cells| igg4 antibodies| major allergen| domestic cat	Reefer, AJ; Carneiro, RM; Custis, NJ; Platts-Mills, TAE; Sung, SSJ; Hammer, J; Woodfolk, JA	A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen		JOURNAL OF IMMUNOLOGY		DELAYED-TYPE HYPERSENSITIVITY; LATE ASTHMATIC REACTIONS; FEL-D-I; MONOCLONAL-ANTIBODIES; POSITIVE ASSOCIATION; SEQUENCE-ANALYSIS; DENDRITIC CELLS; IGG4 ANTIBODIES; MAJOR ALLERGEN; DOMESTIC CAT	Although high dose exposure to inhaled cat allergen (Fel d 1) can cause a form of tolerance (modified Th2 response), the T cell mechanism for this phenomenon has not been studied. T cell responses to Fel d 1 were characterized in both allergic (IgE(pos)) and modified Th2 (IgE(neg)IgG(pos)) responders as well as serum Ab-negative controls (IgE(neg)IgG(neg)). Fel d 1 stimulated high levels of IL-10 in PBMC cultures from all individuals, with evidence of Th2 and Th1 cytokine skewing in allergic and control subjects, respectively. Using overlapping peptides, epitopes at the N terminus of Fel d 1 chain 2 were shown to stimulate strong T cell proliferation and to preferentially induce IL-10 (peptide 2:1 (P2:1)) or IFN-gamma (P2:2) regardless of the allergic status of the donor. Injection of cat extract during conventional immunotherapy stimulated expansion of IL-10- and IFN-gamma-producing chain 2 epitope-specific T cells along with increased Fel d 1-specific serum IgG and IgG4 Ab. Six of 12 modified responders expressed the major HLA-DRB1 allele, *0701, and both P2:1 and P2:2 were predicted ligands for this allele. Cultures from DR7-positive modified responders produced the highest levels of IL-10 to P2:1 in addition to other major and minor epitopes within chains 1 and 2. In the presence of anti-IL-10 mAb, both T cell proliferation and IFN-gamma production were enhanced in a Fel d 1- and epitope-specific manner. We conclude that IL-10-producing T cells specific for chain 2 epitopes are relevant to tolerance induction, and that DR7-restricted recognition of these epitopes favors a modified Th2 response.	55	96	2004	10		Immunology
Developmental cytokine response profiles and the clinical and immunologic expression of atopy during the first year of life. Background: Allergic diseases have been linked to abnormal patterns of immune development, and this has stimulated efforts to define the precise patterns of cytokine dysregulation that are associated with specific atopic phenotypes. Objective: Cytokine-response profiles were prospectively analyzed over the first year of life and compared with the clinical and immunologic expressions of atopy. Methods: Umbilical cord and 1-year PBMCs were obtained from 285 subjects from allergic families. PHA-stimulated cytokine-response profiles (IL-5, IL-10, IL-13, and IFN-gamma) were compared with blood eosinophil counts and total and specific IgE levels (dust mites, cat, egg, Alternaria species, peanut, milk, and dog) at age 1 year and at the development of atopic dermatitis and food allergy. Results: For the cohort as a whole, cytokine responses did not evolve according to a strict T(H)1 or T(H)2 polarization pattern. PHA-stimulated cord blood cells secreted low levels of IL-5 (2.1 pg/mL), moderate levels of IFN-gamma (57.4 pg/mL), and greater amounts of IL-13 (281.8 pg/mL). From birth to 1 year, IL-5 responses dramatically increased, whereas IL-13 and IFN-gamma responses significantly decreased. Reduced cord blood secretion of IL-10 and IFN-gamma was associated with subsequent sensitization to egg. In addition, there was evidence of T(H)2 polarization (increased IL-5 and IL-13 levels) associated with blood eosinophilia and increased total IgE levels by age 1 year. Conclusion: These findings demonstrate that cytokine responses change markedly during the first year of life and provide further evidence of a close relationship between T(H)2 skewing of immune responses and the incidence of atopic manifestations in children.. cytokines| t(h)2| immune development| allergy| ige|interferon-gamma production| common food proteins| subsequent development| ige responses| t-cells| children| allergen| asthma| blood| symptoms.	OCT-2003	cytokines| t(h)2| immune development| allergy| ige|interferon-gamma production| common food proteins| subsequent development| ige responses| t-cells| children| allergen| asthma| blood| symptoms	Neaville, WA; Tisler, C; Bhattacharya, A; Anklam, K; Gilbertson-White, S; Hamilton, R; Adler, K; DaSilva, DF; Roberg, KA; Carlson-Dakes, KT; Anderson, E; Yoshihara, D; Gangnon, R; Mikus, LD; Rosenthal, LA; Gern, JE; Lemanske, RF	Developmental cytokine response profiles and the clinical and immunologic expression of atopy during the first year of life		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	cytokines; T(H)2; immune development; allergy; IgE	INTERFERON-GAMMA PRODUCTION; COMMON FOOD PROTEINS; SUBSEQUENT DEVELOPMENT; IGE RESPONSES; T-CELLS; CHILDREN; ALLERGEN; ASTHMA; BLOOD; SYMPTOMS	Background: Allergic diseases have been linked to abnormal patterns of immune development, and this has stimulated efforts to define the precise patterns of cytokine dysregulation that are associated with specific atopic phenotypes. Objective: Cytokine-response profiles were prospectively analyzed over the first year of life and compared with the clinical and immunologic expressions of atopy. Methods: Umbilical cord and 1-year PBMCs were obtained from 285 subjects from allergic families. PHA-stimulated cytokine-response profiles (IL-5, IL-10, IL-13, and IFN-gamma) were compared with blood eosinophil counts and total and specific IgE levels (dust mites, cat, egg, Alternaria species, peanut, milk, and dog) at age 1 year and at the development of atopic dermatitis and food allergy. Results: For the cohort as a whole, cytokine responses did not evolve according to a strict T(H)1 or T(H)2 polarization pattern. PHA-stimulated cord blood cells secreted low levels of IL-5 (2.1 pg/mL), moderate levels of IFN-gamma (57.4 pg/mL), and greater amounts of IL-13 (281.8 pg/mL). From birth to 1 year, IL-5 responses dramatically increased, whereas IL-13 and IFN-gamma responses significantly decreased. Reduced cord blood secretion of IL-10 and IFN-gamma was associated with subsequent sensitization to egg. In addition, there was evidence of T(H)2 polarization (increased IL-5 and IL-13 levels) associated with blood eosinophilia and increased total IgE levels by age 1 year. Conclusion: These findings demonstrate that cytokine responses change markedly during the first year of life and provide further evidence of a close relationship between T(H)2 skewing of immune responses and the incidence of atopic manifestations in children.	27	96	2003	7	10.1067/mai.2003.1716	Allergy; Immunology
Exposure and sensitization to indoor allergens: Association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma. Background: Exposure to high levels of allergens in sensitized asthmatic patients causes worsening of pulmonary function in experimental studies. Chronic exposure to lower, naturally occurring levels of allergens might increase the severity of asthma. Objective: We sought to study the associations between sensitization and exposure to common indoor allergens (dust mite, cat; and dog) in the home on pulmonary function, exhaled nitric oxide (eNO), and airway reactivity in asthmatic patients. Methods: Dust samples were collected from the living room carpet and mattress of 311 subject's homes, and Der p 1, Fel d 1, and Can f 1 concentrations were measured by using ELISAs. Spirometry, nonspecific bronchial reactivity, and eNO were measured. Results: Subjects both sensitized and exposed to high levels of sensitizing allergen had significantly lower FEV1 percent predicted values (mean, 83.7% vs 89.3%; mean difference, 5.6%; 95% CI, 0.6% -10.6%; P = .03), higher eNO values (geometric mean [GM], 12.8 vs 8.7 ppb; GM ratio, 0.7; 95% CI, 0.5-0.8; P = .001), and more severe airways reactivity (PD20 GM, 0.25 vs 0.73 mg; GM ratio, 2.9; 95% CI, 1.6-5.0; P < .001) compared with subjects not sensitized and exposed. No significant effect of the interaction between sensitization and exposure was found for FEV1 percent predicted and eNO values. However, there was a significant effect of the interaction between sensitization and exposure to any allergen (P = .05) and between sensitization and exposure to cat allergen (P = .04) for nonspecific bronchial reactivity. Conclusion: Asthmatic subjects who are exposed in their homes to allergens to which they are sensitized have a more severe form of the disease.. asthma severity and control| allergen exposure-sensitization| bronchial reactivity| lung function|dust-mite antibodies| childhood asthma| risk-factors| f-i| adults| children| community| decline| hyperresponsiveness| responsiveness.	AUG-2003	asthma severity and control| allergen exposure-sensitization| bronchial reactivity| lung function|dust-mite antibodies| childhood asthma| risk-factors| f-i| adults| children| community| decline| hyperresponsiveness| responsiveness	Langley, SJ; Goldthorpe, S; Craven, M; Morris, J; Woodcock, A; Custovic, A	Exposure and sensitization to indoor allergens: Association with lung function, bronchial reactivity, and exhaled nitric oxide measures in asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma severity and control; allergen exposure-sensitization; bronchial reactivity; lung function	DUST-MITE ANTIBODIES; CHILDHOOD ASTHMA; RISK-FACTORS; F-I; ADULTS; CHILDREN; COMMUNITY; DECLINE; HYPERRESPONSIVENESS; RESPONSIVENESS	Background: Exposure to high levels of allergens in sensitized asthmatic patients causes worsening of pulmonary function in experimental studies. Chronic exposure to lower, naturally occurring levels of allergens might increase the severity of asthma. Objective: We sought to study the associations between sensitization and exposure to common indoor allergens (dust mite, cat; and dog) in the home on pulmonary function, exhaled nitric oxide (eNO), and airway reactivity in asthmatic patients. Methods: Dust samples were collected from the living room carpet and mattress of 311 subject's homes, and Der p 1, Fel d 1, and Can f 1 concentrations were measured by using ELISAs. Spirometry, nonspecific bronchial reactivity, and eNO were measured. Results: Subjects both sensitized and exposed to high levels of sensitizing allergen had significantly lower FEV1 percent predicted values (mean, 83.7% vs 89.3%; mean difference, 5.6%; 95% CI, 0.6% -10.6%; P = .03), higher eNO values (geometric mean [GM], 12.8 vs 8.7 ppb; GM ratio, 0.7; 95% CI, 0.5-0.8; P = .001), and more severe airways reactivity (PD20 GM, 0.25 vs 0.73 mg; GM ratio, 2.9; 95% CI, 1.6-5.0; P < .001) compared with subjects not sensitized and exposed. No significant effect of the interaction between sensitization and exposure was found for FEV1 percent predicted and eNO values. However, there was a significant effect of the interaction between sensitization and exposure to any allergen (P = .05) and between sensitization and exposure to cat allergen (P = .04) for nonspecific bronchial reactivity. Conclusion: Asthmatic subjects who are exposed in their homes to allergens to which they are sensitized have a more severe form of the disease.	36	96	2003	7	10.1067/mai.2003.1654	Allergy; Immunology
Pet-keeping in childhood and adult asthma and hay fever: European Community Respiratory Health Survey. Background: Whether pet-keeping early in life protects against or promotes allergy remains unclear. Objective: Our aim was to examine the effects of childhood pet-keeping on adult allergic disease in a large international population-based study, including information on sensitization, adult pet-keeping, and pet prevalence in the populations. Methods: We used information from structured interviews (n = 18,530) and specific IgE to common aeroallergens in blood samples (n = 13,932) from participants in the European Community Respiratory Health Survey (ECRHS) to analyze the associations between keeping pets and adult asthma and hay fever. Results: Keeping cats in childhood was associated with asthma only among atopic subjects, an association that varied between centers (P = .002) and was stronger where cats where less common (< 40% cats: odds ratio(wheeze) [ORwheeze] = 1.84, 95% CI = 1.31-2.57; 40%-60% cats: ORwheeze = 1.33, 95% CI = 1.10-1.61; greater than or equal to60% cats: ORwheeze = 0.98, 95% CI = 0.73-1.33). Dogs owned in childhood or adulthood were associated with asthma among nonatopic subjects (childhood: ORwheeze = 1.28, 95% CI = 1.13-1.46; adulthood: ORwheeze = 1.31, 95% CI = 1.14-1.51; both: ORwheeze = 1.69, 95% CI = 1.40-2.04). In atopic subjects, those who had owned dogs in childhood had less hay fever (OR = 0.85; 95% CI = 0.73-0.98) and no increased risk of asthma (ORwheeze = 1.01, 95 % CI = 0.87-1.17). Respiratory symptoms were more common in subjects who had owned birds during childhood (ORwheeze = 1.12; 95 % CI = 1.02-1.23) independent of sensitization. Conclusions: The effects of pet-keeping in childhood varied according to the type of pet, the allergic sensitization of the individual, and the wider environmental exposure to allergen. Cats owned in childhood were associated with more asthma in sensitized adults who grew up in areas with a low community prevalence of cats. Dogs owned in childhood seemed to protect against adult allergic disease but promote nonallergic asthma.. cats| dogs| birds| asthma| hay fever| sensitization| tolerance| hygiene hypothesis| ecrhs|house-dust endotoxin| allergen exposure| cat allergens| sensitization| children| symptoms| life| atopy| risk| environment.	AUG-2003	cats| dogs| birds| asthma| hay fever| sensitization| tolerance| hygiene hypothesis| ecrhs|house-dust endotoxin| allergen exposure| cat allergens| sensitization| children| symptoms| life| atopy| risk| environment	Svanes, C; Heinrich, J; Jarvis, D; Chinn, S; Omenaas, E; Gulsvik, A; Kunzli, N; Burney, P	Pet-keeping in childhood and adult asthma and hay fever: European Community Respiratory Health Survey		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	cats; dogs; birds; asthma; hay fever; sensitization; tolerance; hygiene hypothesis; ECRHS	HOUSE-DUST ENDOTOXIN; ALLERGEN EXPOSURE; CAT ALLERGENS; SENSITIZATION; CHILDREN; SYMPTOMS; LIFE; ATOPY; RISK; ENVIRONMENT	Background: Whether pet-keeping early in life protects against or promotes allergy remains unclear. Objective: Our aim was to examine the effects of childhood pet-keeping on adult allergic disease in a large international population-based study, including information on sensitization, adult pet-keeping, and pet prevalence in the populations. Methods: We used information from structured interviews (n = 18,530) and specific IgE to common aeroallergens in blood samples (n = 13,932) from participants in the European Community Respiratory Health Survey (ECRHS) to analyze the associations between keeping pets and adult asthma and hay fever. Results: Keeping cats in childhood was associated with asthma only among atopic subjects, an association that varied between centers (P = .002) and was stronger where cats where less common (< 40% cats: odds ratio(wheeze) [ORwheeze] = 1.84, 95% CI = 1.31-2.57; 40%-60% cats: ORwheeze = 1.33, 95% CI = 1.10-1.61; greater than or equal to60% cats: ORwheeze = 0.98, 95% CI = 0.73-1.33). Dogs owned in childhood or adulthood were associated with asthma among nonatopic subjects (childhood: ORwheeze = 1.28, 95% CI = 1.13-1.46; adulthood: ORwheeze = 1.31, 95% CI = 1.14-1.51; both: ORwheeze = 1.69, 95% CI = 1.40-2.04). In atopic subjects, those who had owned dogs in childhood had less hay fever (OR = 0.85; 95% CI = 0.73-0.98) and no increased risk of asthma (ORwheeze = 1.01, 95 % CI = 0.87-1.17). Respiratory symptoms were more common in subjects who had owned birds during childhood (ORwheeze = 1.12; 95 % CI = 1.02-1.23) independent of sensitization. Conclusions: The effects of pet-keeping in childhood varied according to the type of pet, the allergic sensitization of the individual, and the wider environmental exposure to allergen. Cats owned in childhood were associated with more asthma in sensitized adults who grew up in areas with a low community prevalence of cats. Dogs owned in childhood seemed to protect against adult allergic disease but promote nonallergic asthma.	51	96	2003	12	10.1067/mai.2003.1596	Allergy; Immunology
Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: Latitude, regional ultraviolet radiation, and disease prevalence. The apparent immune-suppressive effect of ultraviolet radiation (UVR) has suggested that this environmental exposure may influence the development of immune-related disorders. Self-reported prevalence rates of type 1 diabetes mellitus, rheumatoid arthritis (RA), eczema/dermatitis, and asthma, from the 1995 Australian National Health Survey, were therefore examined by latitude and ambient level of UVR. A positive association of type I diabetes mellitus prevalence was found with both increasing southern latitude of residence (r = 0.77; P = 0.026) and decreasing regional annual ambient UVR (r = -0.80; p = 0.018); a 3-fold increase in prevalence from the northernmost region to the southernmost region was evident. In contrast, asthma correlated negatively with latitude (r = -0.72; p = 0.046), although the change in asthma prevalence from the north to the south of Australia was only 0.7-fold. For both RA and eczema/dermatitis, there were no statistically significant associations between latitude/UVR and disease prevalence. These ecologic data provide some support for a previously proposed beneficial effect of UVR on T-helper 1-mediated autoimmune disorders such as type 1 diabetes. The inverse association of type 1 diabetes prevalence with UVR is consistent with that previously reported for another autoimmune disease, multiple sclerosis, in Australia, and also with type I diabetes latitudinal gradients in the Northern Hemisphere. The finding also accords with photoimmunologic evidence of UVR-induced immunosuppression and may suggest a beneficial effect of UVR in reducing the incidence of such autoimmune conditions. In light of this study, analytic epidemiologic studies investigating risk of immune disorders in relation to personal UVR exposure in humans are required.. asthma| australia| autoimmune disease| ecologic analysis| eczema/dermatitis| immune disorders| latitude| rheumatoid arthritis| type 1 diabetes| ultraviolet radiation|vitamin-d deficiency| multiple-sclerosis| rheumatoid-arthritis| autoimmune-disease| molecular mimicry| birth-cohort| exposure| mechanisms| responses| asthma.	APR-2003	asthma| australia| autoimmune disease| ecologic analysis| eczema/dermatitis| immune disorders| latitude| rheumatoid arthritis| type 1 diabetes| ultraviolet radiation|vitamin-d deficiency| multiple-sclerosis| rheumatoid-arthritis| autoimmune-disease| molecular mimicry| birth-cohort| exposure| mechanisms| responses| asthma	Staples, JA; Ponsonby, AL; Lim, LLY; McMichael, AJ	Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: Latitude, regional ultraviolet radiation, and disease prevalence		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; Australia; autoimmune disease; ecologic analysis; eczema/dermatitis; immune disorders; latitude; rheumatoid arthritis; type 1 diabetes; ultraviolet radiation	VITAMIN-D DEFICIENCY; MULTIPLE-SCLEROSIS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; MOLECULAR MIMICRY; BIRTH-COHORT; EXPOSURE; MECHANISMS; RESPONSES; ASTHMA	The apparent immune-suppressive effect of ultraviolet radiation (UVR) has suggested that this environmental exposure may influence the development of immune-related disorders. Self-reported prevalence rates of type 1 diabetes mellitus, rheumatoid arthritis (RA), eczema/dermatitis, and asthma, from the 1995 Australian National Health Survey, were therefore examined by latitude and ambient level of UVR. A positive association of type I diabetes mellitus prevalence was found with both increasing southern latitude of residence (r = 0.77; P = 0.026) and decreasing regional annual ambient UVR (r = -0.80; p = 0.018); a 3-fold increase in prevalence from the northernmost region to the southernmost region was evident. In contrast, asthma correlated negatively with latitude (r = -0.72; p = 0.046), although the change in asthma prevalence from the north to the south of Australia was only 0.7-fold. For both RA and eczema/dermatitis, there were no statistically significant associations between latitude/UVR and disease prevalence. These ecologic data provide some support for a previously proposed beneficial effect of UVR on T-helper 1-mediated autoimmune disorders such as type 1 diabetes. The inverse association of type 1 diabetes prevalence with UVR is consistent with that previously reported for another autoimmune disease, multiple sclerosis, in Australia, and also with type I diabetes latitudinal gradients in the Northern Hemisphere. The finding also accords with photoimmunologic evidence of UVR-induced immunosuppression and may suggest a beneficial effect of UVR in reducing the incidence of such autoimmune conditions. In light of this study, analytic epidemiologic studies investigating risk of immune disorders in relation to personal UVR exposure in humans are required.	55	96	2003	6	10.1289/ehp.5941	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Improving the health of workers in indoor environments: Priority research needs for a national occupational research agenda. Indoor nonindustrial work environments were designated a priority research area through the nationwide stakeholder process that created the National Occupational Research Agenda. A multidisciplinary research team used member consensus and quantitative estimates, with extensive external review, to develop a specific research agenda. The team outlined the following priority research topics: building-influenced communicable respiratory infections, building-related asthma/allergic diseases, and nonspecific building-related symptoms; indoor environmental science; and methods for increasing implementation of healthful building practices. Available data suggest that improving building environments may result in health benefits for more than 15 million of the 89 million US indoor workers, with estimated economic benefits of $5 to $75 billion annually. Research on these topics, requiring new collaborations and resources, offers enormous potential health and economic returns.. sick-building-syndrome| air exchange-rate| office buildings| respiratory-diseases| rhinovirus colds| ventilation| risk| transmission| asthma| infections.	SEP-2002	sick-building-syndrome| air exchange-rate| office buildings| respiratory-diseases| rhinovirus colds| ventilation| risk| transmission| asthma| infections	Mendell, MJ; Fisk, WJ; Kreiss, K; Levin, H; Alexander, D; Cain, WS; Girman, JR; Hines, CJ; Jensen, PA; Milton, DK; Rexroat, LP; Wallingford, KM	Improving the health of workers in indoor environments: Priority research needs for a national occupational research agenda		AMERICAN JOURNAL OF PUBLIC HEALTH		SICK-BUILDING-SYNDROME; AIR EXCHANGE-RATE; OFFICE BUILDINGS; RESPIRATORY-DISEASES; RHINOVIRUS COLDS; VENTILATION; RISK; TRANSMISSION; ASTHMA; INFECTIONS	Indoor nonindustrial work environments were designated a priority research area through the nationwide stakeholder process that created the National Occupational Research Agenda. A multidisciplinary research team used member consensus and quantitative estimates, with extensive external review, to develop a specific research agenda. The team outlined the following priority research topics: building-influenced communicable respiratory infections, building-related asthma/allergic diseases, and nonspecific building-related symptoms; indoor environmental science; and methods for increasing implementation of healthful building practices. Available data suggest that improving building environments may result in health benefits for more than 15 million of the 89 million US indoor workers, with estimated economic benefits of $5 to $75 billion annually. Research on these topics, requiring new collaborations and resources, offers enormous potential health and economic returns.	73	96	2002	11	10.2105/AJPH.92.9.1430	Public, Environmental & Occupational Health
Airway complications associated with surgery on the anterior cervical spine. Study Design. Retrospective chart review of 311 anterior cervical procedures. Objectives. To assess the incidence and variables that predispose to an airway complication in a large series of anterior cervical surgical procedures. Summary of Background Data. A rare but potentially lethal complication after anterior cervical spine surgery is respiratory compromise and airway obstruction, Some risk factors are thought to include two-level corpectomy in myelopathic patients with a history of heavy smoking and asthma. No previous study in the literature has been directed at examining the factors specifically related to airway complications after anterior cervical spine surgery, Methods. Each chart was examined for patient characteristics and pathology, anesthetic parameters and problems, operative procedure, and postoperative course and management. Statistical analysis was performed. Results. Nineteen patients (6.1%) had an airway complication and six (1.9%) required reintubation. One patient died. Symptoms developed on average 36 hours postoperatively. All complications except for two were attributable to pharyngeal edema. Variables that were found to be statistically associated with an airway complication (P < 0.05) were exposing more than three vertebral bodies, a blood loss >300 mL, exposures involving C2, C3, or C4, and an operative time >5 hours. A history of myelopathy, spinal cord injury, pulmonary problems, smoking, anesthetic risk factors, and the absence of a drain did not correlate with an airway complication, Conclusions. Patients with prolonged procedures (i.e., >5 hours) exposing more than three vertebral levels that include C2, C3, or C4 with more than 300-mL blood loss should be watched carefully for respiratory insufficiency.. airway| respiratory| complications| anterior cervical surgery|vocal cord paralysis| caspar instrumentation| plate fixation| fusion| obstruction| injury| stabilization| diskectomy| corpectomy| dysphagia.	MAY 1-2002	airway| respiratory| complications| anterior cervical surgery|vocal cord paralysis| caspar instrumentation| plate fixation| fusion| obstruction| injury| stabilization| diskectomy| corpectomy| dysphagia	Sagi, HC; Beutler, W; Carroll, E; Connolly, PJ	Airway complications associated with surgery on the anterior cervical spine		SPINE	airway; respiratory; complications; anterior cervical surgery	VOCAL CORD PARALYSIS; CASPAR INSTRUMENTATION; PLATE FIXATION; FUSION; OBSTRUCTION; INJURY; STABILIZATION; DISKECTOMY; CORPECTOMY; DYSPHAGIA	Study Design. Retrospective chart review of 311 anterior cervical procedures. Objectives. To assess the incidence and variables that predispose to an airway complication in a large series of anterior cervical surgical procedures. Summary of Background Data. A rare but potentially lethal complication after anterior cervical spine surgery is respiratory compromise and airway obstruction, Some risk factors are thought to include two-level corpectomy in myelopathic patients with a history of heavy smoking and asthma. No previous study in the literature has been directed at examining the factors specifically related to airway complications after anterior cervical spine surgery, Methods. Each chart was examined for patient characteristics and pathology, anesthetic parameters and problems, operative procedure, and postoperative course and management. Statistical analysis was performed. Results. Nineteen patients (6.1%) had an airway complication and six (1.9%) required reintubation. One patient died. Symptoms developed on average 36 hours postoperatively. All complications except for two were attributable to pharyngeal edema. Variables that were found to be statistically associated with an airway complication (P < 0.05) were exposing more than three vertebral bodies, a blood loss >300 mL, exposures involving C2, C3, or C4, and an operative time >5 hours. A history of myelopathy, spinal cord injury, pulmonary problems, smoking, anesthetic risk factors, and the absence of a drain did not correlate with an airway complication, Conclusions. Patients with prolonged procedures (i.e., >5 hours) exposing more than three vertebral levels that include C2, C3, or C4 with more than 300-mL blood loss should be watched carefully for respiratory insufficiency.	31	96	2002	5	10.1097/00007632-200205010-00013	Neurosciences & Neurology; Orthopedics
Chemical predictors of wheeze among farmer pesticide applicators in the agricultural health study. Pesticides may contribute to respiratory symptoms among farmers. Using the Agricultural Health Study, a large cohort of certified pesticide applicators in Iowa and North Carolina, we explored the association between wheeze and pesticide use in the past year. Self-administered questionnaires contained items on 40 currently used pesticides and pesticide application practices. A total of 20,468 applicators, ranging in age from 16 to 88 years, provided complete information; 19% reported wheezing in the past year. Logistic regression models controlling for age, state, smoking, and history of asthma or atopy were used to evaluate associations between individual pesticides and wheeze. Among pesticides suspected to contribute to wheeze, paraquat, three organophosphates (parathion, malathion, and chlorpyrifos), and one thiocarbamate (S-ethyl-dipropylthiocarbamate [EPTC]) had elevated odds ratios (OR). Parathion had the highest OR (1.5, 95% confidence interval [CI] 1.0, 2.2). Chlorpyrifos, EPTC, paraquat, and parathion demonstrated significant dose-response trends. The herbicides, atrazine and alachlor, but not 2,4-D, were associated with wheeze. Atrazine had a significant dose-response trend with participants applying atrazine more than 20 days/year having an OR of 1.5 (95% CI 1.2, 1.9). Inclusion of crops and animals into these models did not significantly alter the observed OR. These associations, though small, suggest an independent role for specific pesticides in respiratory symptoms of farmers.. wheeze| pesticides| organophosphates| paraquat| agricultural exposure|respiratory symptoms| occupational asthma| paraquat| workers| insecticide| population| prevalence| selection| exposure| industry.	MAR 1-2002	wheeze| pesticides| organophosphates| paraquat| agricultural exposure|respiratory symptoms| occupational asthma| paraquat| workers| insecticide| population| prevalence| selection| exposure| industry	Hoppin, JA; Umbach, DM; London, SJ; Alavanja, MCR; Sandler, DP	Chemical predictors of wheeze among farmer pesticide applicators in the agricultural health study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	wheeze; pesticides; organophosphates; paraquat; agricultural exposure	RESPIRATORY SYMPTOMS; OCCUPATIONAL ASTHMA; PARAQUAT; WORKERS; INSECTICIDE; POPULATION; PREVALENCE; SELECTION; EXPOSURE; INDUSTRY	Pesticides may contribute to respiratory symptoms among farmers. Using the Agricultural Health Study, a large cohort of certified pesticide applicators in Iowa and North Carolina, we explored the association between wheeze and pesticide use in the past year. Self-administered questionnaires contained items on 40 currently used pesticides and pesticide application practices. A total of 20,468 applicators, ranging in age from 16 to 88 years, provided complete information; 19% reported wheezing in the past year. Logistic regression models controlling for age, state, smoking, and history of asthma or atopy were used to evaluate associations between individual pesticides and wheeze. Among pesticides suspected to contribute to wheeze, paraquat, three organophosphates (parathion, malathion, and chlorpyrifos), and one thiocarbamate (S-ethyl-dipropylthiocarbamate [EPTC]) had elevated odds ratios (OR). Parathion had the highest OR (1.5, 95% confidence interval [CI] 1.0, 2.2). Chlorpyrifos, EPTC, paraquat, and parathion demonstrated significant dose-response trends. The herbicides, atrazine and alachlor, but not 2,4-D, were associated with wheeze. Atrazine had a significant dose-response trend with participants applying atrazine more than 20 days/year having an OR of 1.5 (95% CI 1.2, 1.9). Inclusion of crops and animals into these models did not significantly alter the observed OR. These associations, though small, suggest an independent role for specific pesticides in respiratory symptoms of farmers.	32	96	2002	7	10.1164/rccm.2106074	General & Internal Medicine; Respiratory System
Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells. Interleukin (IL)-13 has been associated with asthma, allergic rhinitis, and chronic sinusitis, all conditions where an imbalance in epithelial fluid secretion and absorption could impact upon the disease. We have investigated the effects of IL-13 on the ion transport characteristics of human bronchial epithelial cells cultured at an apical-air interface. Ussing chamber studies indicated that 48 h pretreatment with IL-13 or IL-4 significantly reduced the basal short-circuit current (I-sc) and inhibited the amiloride-sensitive current by >98%. Furthermore, the I-sc responses were increased by more than six- and twofold over control values when stimulated with UTP or forskolin, respectively, after cytokine treatment. The IL-13-enhanced response to UTP/ionomycin was sensitive to bumetanide and DIDS and was reduced in a low-chloride, bicarbonate-free solution. Membrane permeablization studies indicated that IL-13 induced the functional expression of an apical Ca2+-activated anion conductance and that changes in apical or basolateral K+ conductances could not account for the increased I-sc responses to UTP or ionomycin. The results indicate that IL-13 converts the human bronchial epithelium from an absorptive to a secretory phenotype that is the result of loss of amiloride-sensitive current and an increase in a DIDS-sensitive apical anion conductance.. calcium-activated chloride channel| hypersecretion| asthma| interleukin-4|transmembrane conductance regulator| airway epithelium| wild-type| expression| asthma| channel| differentiation| modulation| mediators| il-13.	FEB-2002	calcium-activated chloride channel| hypersecretion| asthma| interleukin-4|transmembrane conductance regulator| airway epithelium| wild-type| expression| asthma| channel| differentiation| modulation| mediators| il-13	Danahay, H; Atherton, H; Jones, G; Bridges, RJ; Poll, CT	Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells		AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY	calcium-activated chloride channel; hypersecretion; asthma; interleukin-4	TRANSMEMBRANE CONDUCTANCE REGULATOR; AIRWAY EPITHELIUM; WILD-TYPE; EXPRESSION; ASTHMA; CHANNEL; DIFFERENTIATION; MODULATION; MEDIATORS; IL-13	Interleukin (IL)-13 has been associated with asthma, allergic rhinitis, and chronic sinusitis, all conditions where an imbalance in epithelial fluid secretion and absorption could impact upon the disease. We have investigated the effects of IL-13 on the ion transport characteristics of human bronchial epithelial cells cultured at an apical-air interface. Ussing chamber studies indicated that 48 h pretreatment with IL-13 or IL-4 significantly reduced the basal short-circuit current (I-sc) and inhibited the amiloride-sensitive current by >98%. Furthermore, the I-sc responses were increased by more than six- and twofold over control values when stimulated with UTP or forskolin, respectively, after cytokine treatment. The IL-13-enhanced response to UTP/ionomycin was sensitive to bumetanide and DIDS and was reduced in a low-chloride, bicarbonate-free solution. Membrane permeablization studies indicated that IL-13 induced the functional expression of an apical Ca2+-activated anion conductance and that changes in apical or basolateral K+ conductances could not account for the increased I-sc responses to UTP or ionomycin. The results indicate that IL-13 converts the human bronchial epithelium from an absorptive to a secretory phenotype that is the result of loss of amiloride-sensitive current and an increase in a DIDS-sensitive apical anion conductance.	39	96	2002	11		Physiology; Respiratory System
Effects of in utero and environmental tobacco smoke exposure on lung function in boys and girls with and without asthma. To investigate whether the effects of in utero exposure to maternal smoking and environmental tobacco smoke (ETS) exposure on lung function vary by sex or asthma status, we examined medical history and tobacco smoke exposure data for 5,263 participants in the Children's Health Study. At study enrollment, parents or guardians of each subject completed a questionnaire, and lung function was measured spirometrically with maximum forced expiratory flow-volume maneuvers. To assess the in utero effects of maternal smoking and ETS exposure on lung function, we used regression splines that accounted for the nonlinear relationship between pulmonary function, height, and age. In utero exposure to maternal smoking was independently associated with deficits in lung function that were larger for children with asthma. Boys and girls with a history of in utero exposure to maternal smoking showed deficits in maximum midexpiratory flow (MMEF) and a decrease in the FEV1/FVC ratio. As compared with children without asthma, boys with asthma had significantly larger deficits from in utero exposure in FVC, MMEF, and FEV1/FVC, and girls with asthma had larger decreases in FEV1/FVC. The effect of ETS exposure varied by children's gender and asthma status. Deficits in flows associated with current ETS exposure were present in children with and without asthma but were significant only among children without asthma. Past ETS exposure was associated with reduced FEV1, MMEF, and FEV1/FVC among boys with asthma. In contrast, past ETS exposure was associated with decreased flow rates in girls without asthma. In summary, both in utero exposure to maternal smoking and ETS exposure were associated with persistent deficits in lung function. The effects of in utero exposure were greatest among children with asthma.. southern california communities| maternal smoking| pulmonary-function| cigarette-smoking| parental smoking| passive smoking| respiratory illness| differing levels| air-pollution| children.	DEC-2000	southern california communities| maternal smoking| pulmonary-function| cigarette-smoking| parental smoking| passive smoking| respiratory illness| differing levels| air-pollution| children	Li, YF; Gilliland, FD; Berhane, K; McConnell, R; Gauderman, WJ; Rappaport, EB; Peters, JM	Effects of in utero and environmental tobacco smoke exposure on lung function in boys and girls with and without asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		SOUTHERN CALIFORNIA COMMUNITIES; MATERNAL SMOKING; PULMONARY-FUNCTION; CIGARETTE-SMOKING; PARENTAL SMOKING; PASSIVE SMOKING; RESPIRATORY ILLNESS; DIFFERING LEVELS; AIR-POLLUTION; CHILDREN	To investigate whether the effects of in utero exposure to maternal smoking and environmental tobacco smoke (ETS) exposure on lung function vary by sex or asthma status, we examined medical history and tobacco smoke exposure data for 5,263 participants in the Children's Health Study. At study enrollment, parents or guardians of each subject completed a questionnaire, and lung function was measured spirometrically with maximum forced expiratory flow-volume maneuvers. To assess the in utero effects of maternal smoking and ETS exposure on lung function, we used regression splines that accounted for the nonlinear relationship between pulmonary function, height, and age. In utero exposure to maternal smoking was independently associated with deficits in lung function that were larger for children with asthma. Boys and girls with a history of in utero exposure to maternal smoking showed deficits in maximum midexpiratory flow (MMEF) and a decrease in the FEV1/FVC ratio. As compared with children without asthma, boys with asthma had significantly larger deficits from in utero exposure in FVC, MMEF, and FEV1/FVC, and girls with asthma had larger decreases in FEV1/FVC. The effect of ETS exposure varied by children's gender and asthma status. Deficits in flows associated with current ETS exposure were present in children with and without asthma but were significant only among children without asthma. Past ETS exposure was associated with reduced FEV1, MMEF, and FEV1/FVC among boys with asthma. In contrast, past ETS exposure was associated with decreased flow rates in girls without asthma. In summary, both in utero exposure to maternal smoking and ETS exposure were associated with persistent deficits in lung function. The effects of in utero exposure were greatest among children with asthma.	42	96	2000	8		General & Internal Medicine; Respiratory System
Effect of outdoor and indoor nitrogen dioxide on respiratory symptoms in schoolchildren. Background Nitrogen dioxide (NO2), an oxidant gas that contaminates both outdoor and indoor air, is considered to be a potential risk factor for asthma. We investigated concurrently the effects of outdoor and indoor NO2 on the prevalence and incidence of respiratory symptoms among children. Methods A cohort study was carried out over 3 years on 842 schoolchildren living in seven different communities in Japan. Indoor NO2. concentrations over 24 hours were measured in both winter and summer in. the homes of the subjects, and a 3-year average of the outdoor NO2 concentration was determined for each community. Respiratory symptoms were evaluated every year from responses to questionnaires. Results The prevalence of bronchitis, wheeze, and asthma significantly increased with increases of indoor NO2 concentrations among girls, but not among boys. In neither boys nor girls were there significant differences in the prevalence of respiratory symptoms among urban, suburban, and rural districts. The incidence of asthma increased among children living in areas with high concentrations of outdoor NO2 Multiple logistic regression analysis showed that a 10 parts per billion (ppb) increase of outdoor NO2 concentration was associated with an increased incidence of wheeze and asthma (odds ratios [OR] = 1.76, 95% CI : 1.04-3.23 and OR = 2.10, 95% CI: 1.10-4.75, respectively), but that no such associations were found with indoor NO2 concentration (OR = 0.73, 95% CI:0.45-1.14 and OR = 0.87, 95% CI:0.51-1.43,respectively). Conclusions These findings suggest that outdoor NO2 air pollution may be particularly important for the development of wheeze and asthma among children. Indoor NO2 concentrations were associated with the prevalence of respiratory symptoms only among girls. Girls may be more susceptible to indoor air pollution than boys.. nitrogen dioxide| air pollution| indoor environment| wheeze| asthma| cohort study|air-pollution| childhood asthma| inhaled allergen| lung-function| east-germany| children| exposure| health| association| prevalence.	OCT-2000	nitrogen dioxide| air pollution| indoor environment| wheeze| asthma| cohort study|air-pollution| childhood asthma| inhaled allergen| lung-function| east-germany| children| exposure| health| association| prevalence	Shima, M; Adachi, M	Effect of outdoor and indoor nitrogen dioxide on respiratory symptoms in schoolchildren		INTERNATIONAL JOURNAL OF EPIDEMIOLOGY	nitrogen dioxide; air pollution; indoor environment; wheeze; asthma; cohort study	AIR-POLLUTION; CHILDHOOD ASTHMA; INHALED ALLERGEN; LUNG-FUNCTION; EAST-GERMANY; CHILDREN; EXPOSURE; HEALTH; ASSOCIATION; PREVALENCE	Background Nitrogen dioxide (NO2), an oxidant gas that contaminates both outdoor and indoor air, is considered to be a potential risk factor for asthma. We investigated concurrently the effects of outdoor and indoor NO2 on the prevalence and incidence of respiratory symptoms among children. Methods A cohort study was carried out over 3 years on 842 schoolchildren living in seven different communities in Japan. Indoor NO2. concentrations over 24 hours were measured in both winter and summer in. the homes of the subjects, and a 3-year average of the outdoor NO2 concentration was determined for each community. Respiratory symptoms were evaluated every year from responses to questionnaires. Results The prevalence of bronchitis, wheeze, and asthma significantly increased with increases of indoor NO2 concentrations among girls, but not among boys. In neither boys nor girls were there significant differences in the prevalence of respiratory symptoms among urban, suburban, and rural districts. The incidence of asthma increased among children living in areas with high concentrations of outdoor NO2 Multiple logistic regression analysis showed that a 10 parts per billion (ppb) increase of outdoor NO2 concentration was associated with an increased incidence of wheeze and asthma (odds ratios [OR] = 1.76, 95% CI : 1.04-3.23 and OR = 2.10, 95% CI: 1.10-4.75, respectively), but that no such associations were found with indoor NO2 concentration (OR = 0.73, 95% CI:0.45-1.14 and OR = 0.87, 95% CI:0.51-1.43,respectively). Conclusions These findings suggest that outdoor NO2 air pollution may be particularly important for the development of wheeze and asthma among children. Indoor NO2 concentrations were associated with the prevalence of respiratory symptoms only among girls. Girls may be more susceptible to indoor air pollution than boys.	41	96	2000	9	10.1093/ije/29.5.862	Public, Environmental & Occupational Health
Direct evidence for transplacental allergen transfer. Allergies are increasing, and despite deeper insights into the immunologic basis of these diseases, preventive measures are not yet efficient. As the induction of allergic diseases is often triggered in early childhood, perinatal or prenatal preventive strategies would be beneficial. We investigated the transfer of inhalant and nutritive allergens across the human placenta. For this purpose, the maternal side of a placental cotyledon was perfused in vitro with an allergen-containing medium, and a specific ELISA was used to detect the allergens on the fetal side. Both allergens evaluated, birch pollen major allergen Bet vl and the milk allergen beta-lactoglobulin, could be shown to cross the placenta. The nutritive allergen beta-lactoglobulin was not only transferred across the placenta in all eight experiments, but was also detectable within the first minutes of perfusion. The peak allergen concentration on the fetal side could be increased by addition of human immunoglobulin. Far the inhalant allergen Bet v1, transfer was observed in two of 10 placental experiments, and only if human immunoglobulin was added. a pulsatility wave with a frequency of 30-35 min suggested tin active transfer mechanism We conclude that allergens are actively and selectively transferred across the placenta. Therefore, controlled maternal allergen exposure might offer new ways to induce tolerance to specific allergens in the fetus.. cell proliferative responses| perfused human placenta| environmental allergens| babies born| responsiveness| childhood| proteins| newborns| antigens| patterns.	SEP-2000	cell proliferative responses| perfused human placenta| environmental allergens| babies born| responsiveness| childhood| proteins| newborns| antigens| patterns	Szepfalusi, Z; Loibichler, C; Pichler, J; Reisenberger, K; Ebner, C; Urbanek, R	Direct evidence for transplacental allergen transfer		PEDIATRIC RESEARCH		CELL PROLIFERATIVE RESPONSES; PERFUSED HUMAN PLACENTA; ENVIRONMENTAL ALLERGENS; BABIES BORN; RESPONSIVENESS; CHILDHOOD; PROTEINS; NEWBORNS; ANTIGENS; PATTERNS	Allergies are increasing, and despite deeper insights into the immunologic basis of these diseases, preventive measures are not yet efficient. As the induction of allergic diseases is often triggered in early childhood, perinatal or prenatal preventive strategies would be beneficial. We investigated the transfer of inhalant and nutritive allergens across the human placenta. For this purpose, the maternal side of a placental cotyledon was perfused in vitro with an allergen-containing medium, and a specific ELISA was used to detect the allergens on the fetal side. Both allergens evaluated, birch pollen major allergen Bet vl and the milk allergen beta-lactoglobulin, could be shown to cross the placenta. The nutritive allergen beta-lactoglobulin was not only transferred across the placenta in all eight experiments, but was also detectable within the first minutes of perfusion. The peak allergen concentration on the fetal side could be increased by addition of human immunoglobulin. Far the inhalant allergen Bet v1, transfer was observed in two of 10 placental experiments, and only if human immunoglobulin was added. a pulsatility wave with a frequency of 30-35 min suggested tin active transfer mechanism We conclude that allergens are actively and selectively transferred across the placenta. Therefore, controlled maternal allergen exposure might offer new ways to induce tolerance to specific allergens in the fetus.	25	96	2000	4		Pediatrics
Atopy, lung function, and obstructive airways disease after prenatal exposure to famine. Background-Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944-5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy. Methods-Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants). Results-Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI: 0.9 to 2.6). Conclusions The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.. fetal origins of disease| atopy| obstructive airways disease| famine|birth-weight| risk-factors| fetal growth| adult-rats| asthma| childhood| ige| adolescence| prevalence| allergens.	JUL-2000	fetal origins of disease| atopy| obstructive airways disease| famine|birth-weight| risk-factors| fetal growth| adult-rats| asthma| childhood| ige| adolescence| prevalence| allergens	Lopuhaa, CE; Roseboom, TJ; Osmond, C; Barker, DJP; Ravelli, ACJ; Bleker, OP; van der Zee, JS; van der Meulen, JHP	Atopy, lung function, and obstructive airways disease after prenatal exposure to famine		THORAX	fetal origins of disease; atopy; obstructive airways disease; famine	BIRTH-WEIGHT; RISK-FACTORS; FETAL GROWTH; ADULT-RATS; ASTHMA; CHILDHOOD; IGE; ADOLESCENCE; PREVALENCE; ALLERGENS	Background-Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944-5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy. Methods-Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants). Results-Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI: 0.9 to 2.6). Conclusions The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.	36	96	2000	7	10.1136/thorax.55.7.555	Respiratory System
House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection. Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c(+)/CD11b(+) and CD11c(+)/CD8(+) cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.. house environment| airway adaptive immunity| gastrointestinal bacterial community| lactobacilliaceae|t-cells| childhood| risk| mice| suppresses| metabolism| bacteria| infancy.	JAN 14-2014	house environment| airway adaptive immunity| gastrointestinal bacterial community| lactobacilliaceae|t-cells| childhood| risk| mice| suppresses| metabolism| bacteria| infancy	Fujimura, KE; Demoor, T; Rauch, M; Faruqi, AA; Jang, S; Johnson, CC; Boushey, HA; Zoratti, E; Ownby, D; Lukacs, NW; Lynch, SV	House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	house environment; airway adaptive immunity; gastrointestinal bacterial community; Lactobacilliaceae	T-CELLS; CHILDHOOD; RISK; MICE; SUPPRESSES; METABOLISM; BACTERIA; INFANCY	Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c(+)/CD11b(+) and CD11c(+)/CD8(+) cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.	30	95	2014	6	10.1073/pnas.1310750111	Science & Technology - Other Topics
Interaction between Asthma and Lung Function Growth in Early Life. Rationale: The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma. Objectives: To analyze the interaction between lung function development and asthma from birth to 7 years of age. Methods: The Copenhagen Prospective Studies on Asthma in Childhood is a prospective clinical study of a birth cohort of 411 at-risk children. Spirometry was completed in 403 (98%) neonates and again by age 7 in 317 children (77%). Measurements and Main Results: Neonatal spirometry and bronchial responsiveness to methacholine was measured during sedation by forced flow-volume measurements. Asthma was diagnosed prospectively from daily diary cards and clinic visits every 6 months. Children with asthma by age 7(14%) already had a significant airflow deficit as neonates (forced expiratory flow at 50% of vital capacity second in neonates reduced by 0.34 z score by 1 mo; P = 0.03). This deficit progressed significantly during early childhood (forced expiratory flow at 0.5 seconds in neonates at age 7 reduced by 0.82 z score by age 7; P < 0.0001), suggesting that approximately 40% of the airflow deficit associated with asthma is present at birth, whereas 60% develops with clinical disease. Environmental tobacco exposure, but not allergic sensitization, also hampered airflow growth. Bronchial responsiveness to methacholine in the neonates was associated with the development of asthma (P = 0.01). Conclusions: Children developing asthma by age 7 had a lung function deficit and increased bronchial responsiveness as neonates. This lung function deficit progressed to age 7. Therefore, research into the origins and prevention of asthma should consider early life before and after birth.. asthma| lung function| young child| infant| neonate|1st 6 years| airway responsiveness| preschool-children| childhood asthma| birth cohort| high-risk| bronchial responsiveness| inhaled corticosteroids| young infants| long-term.	JUN 1-2012	asthma| lung function| young child| infant| neonate|1st 6 years| airway responsiveness| preschool-children| childhood asthma| birth cohort| high-risk| bronchial responsiveness| inhaled corticosteroids| young infants| long-term	Bisgaard, H; Jensen, SM; Bonnelykke, K	Interaction between Asthma and Lung Function Growth in Early Life		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; lung function; young child; infant; neonate	1ST 6 YEARS; AIRWAY RESPONSIVENESS; PRESCHOOL-CHILDREN; CHILDHOOD ASTHMA; BIRTH COHORT; HIGH-RISK; BRONCHIAL RESPONSIVENESS; INHALED CORTICOSTEROIDS; YOUNG INFANTS; LONG-TERM	Rationale: The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma. Objectives: To analyze the interaction between lung function development and asthma from birth to 7 years of age. Methods: The Copenhagen Prospective Studies on Asthma in Childhood is a prospective clinical study of a birth cohort of 411 at-risk children. Spirometry was completed in 403 (98%) neonates and again by age 7 in 317 children (77%). Measurements and Main Results: Neonatal spirometry and bronchial responsiveness to methacholine was measured during sedation by forced flow-volume measurements. Asthma was diagnosed prospectively from daily diary cards and clinic visits every 6 months. Children with asthma by age 7(14%) already had a significant airflow deficit as neonates (forced expiratory flow at 50% of vital capacity second in neonates reduced by 0.34 z score by 1 mo; P = 0.03). This deficit progressed significantly during early childhood (forced expiratory flow at 0.5 seconds in neonates at age 7 reduced by 0.82 z score by age 7; P < 0.0001), suggesting that approximately 40% of the airflow deficit associated with asthma is present at birth, whereas 60% develops with clinical disease. Environmental tobacco exposure, but not allergic sensitization, also hampered airflow growth. Bronchial responsiveness to methacholine in the neonates was associated with the development of asthma (P = 0.01). Conclusions: Children developing asthma by age 7 had a lung function deficit and increased bronchial responsiveness as neonates. This lung function deficit progressed to age 7. Therefore, research into the origins and prevention of asthma should consider early life before and after birth.	33	95	2012	7	10.1164/rccm.201110-1922OC	General & Internal Medicine; Respiratory System
Daily or Intermittent Budesonide in Preschool Children with Recurrent Wheezing. BACKGROUND Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy. METHODS We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy. RESULTS The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P = 0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen. CONCLUSIONS A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.). inhaled fluticasone propionate| randomized controlled-trial| 2 years old| young-children| inhalation suspension| persistent asthma| oral prednisolone| double-blind| infants| corticosteroids.	NOV 24-2011	inhaled fluticasone propionate| randomized controlled-trial| 2 years old| young-children| inhalation suspension| persistent asthma| oral prednisolone| double-blind| infants| corticosteroids	Zeiger, RS; Mauger, D; Bacharier, LB; Guilbert, TW; Martinez, FD; Lemanske, RF; Strunk, RC; Covar, R; Szefler, SJ; Boehmer, S; Jackson, DJ; Sorkness, CA; Gern, JE; Kelly, HW; Friedman, NJ; Mellon, MH; Schatz, M; Morgan, WJ; Chinchilli, VM; Raissy, HH; Bade, E; Malka-Rais, J; Beigelman, A; Taussig, LM	Daily or Intermittent Budesonide in Preschool Children with Recurrent Wheezing		NEW ENGLAND JOURNAL OF MEDICINE		INHALED FLUTICASONE PROPIONATE; RANDOMIZED CONTROLLED-TRIAL; 2 YEARS OLD; YOUNG-CHILDREN; INHALATION SUSPENSION; PERSISTENT ASTHMA; ORAL PREDNISOLONE; DOUBLE-BLIND; INFANTS; CORTICOSTEROIDS	BACKGROUND Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy. METHODS We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy. RESULTS The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P = 0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen. CONCLUSIONS A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.)	39	95	2011	12		General & Internal Medicine
Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5(+) T(H)2 cells. Mouse CCL8 is a CC chemokine of the monocyte chemoattractant protein (MCP) family whose biological activity and receptor usage have remained elusive. Here we show that CCL8 is highly expressed in the skin, where it serves as an agonist for the chemokine receptor CCR8 but not for CCR2. This distinguishes CCL8 from all other MCP chemokines. CCL8 responsiveness defined a population of highly differentiated, CCR8-expressing inflammatory T helper type 2 (T(H)2) cells enriched for interleukin (IL)-5. Ccr8- and Ccl8-deficient mice had markedly less eosinophilic inflammation than wild-type or Ccr4-deficient mice in a model of chronic atopic dermatitis. Adoptive transfer studies established CCR8 as a key regulator of T(H)2 cell recruitment into allergen-inflamed skin. In humans, CCR8 expression also defined an IL-5-enriched T(H)2 cell subset. The CCL8-CCR8 chemokine axis is therefore a crucial regulator of T(H)2 cell homing that drives IL-5-mediated chronic allergic inflammation.. chemokine receptor ccr8| t-cells| dendritic cells| airway inflammation| immune-responses| cutting edge| th1 cells| in-vivo| expression| differentiation.	FEB-2011	chemokine receptor ccr8| t-cells| dendritic cells| airway inflammation| immune-responses| cutting edge| th1 cells| in-vivo| expression| differentiation	Islam, SA; Chang, DS; Colvin, RA; Byrne, MH; McCully, ML; Moser, B; Lira, SA; Charo, IF; Luster, AD	Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5(+) T(H)2 cells		NATURE IMMUNOLOGY		CHEMOKINE RECEPTOR CCR8; T-CELLS; DENDRITIC CELLS; AIRWAY INFLAMMATION; IMMUNE-RESPONSES; CUTTING EDGE; TH1 CELLS; IN-VIVO; EXPRESSION; DIFFERENTIATION	Mouse CCL8 is a CC chemokine of the monocyte chemoattractant protein (MCP) family whose biological activity and receptor usage have remained elusive. Here we show that CCL8 is highly expressed in the skin, where it serves as an agonist for the chemokine receptor CCR8 but not for CCR2. This distinguishes CCL8 from all other MCP chemokines. CCL8 responsiveness defined a population of highly differentiated, CCR8-expressing inflammatory T helper type 2 (T(H)2) cells enriched for interleukin (IL)-5. Ccr8- and Ccl8-deficient mice had markedly less eosinophilic inflammation than wild-type or Ccr4-deficient mice in a model of chronic atopic dermatitis. Adoptive transfer studies established CCR8 as a key regulator of T(H)2 cell recruitment into allergen-inflamed skin. In humans, CCR8 expression also defined an IL-5-enriched T(H)2 cell subset. The CCL8-CCR8 chemokine axis is therefore a crucial regulator of T(H)2 cell homing that drives IL-5-mediated chronic allergic inflammation.	50	95	2011	13	10.1038/ni.1984	Immunology
Environmental epigenetics of asthma: An update. Asthma, a chronic inflammatory disorder of the airway, is influenced by interplay between genetic and environmental factors now known to be mediated by epigenetics. Aberrant DNA methylation, altered histone modifications, specific microRNA expression, and other chromatin alterations orchestrate a complex early-life reprogramming of immune T-cell response, dendritic cell function, macrophage activation, and a breach of airway epithelial barrier that dictates asthma risk and severity in later life. Adult-onset asthma is under analogous regulation. The sharp increase in asthma prevalence over the past 2 or 3 decades and the large variations among populations of similar racial/ethnic background but different environmental exposures favors a strong contribution of environmental factors. This review addresses the fundamental question of whether environmental influences on asthma risk, severity, and steroid resistance are partly due to differential epigenetic modulations. Current knowledge on the epigenetic effects of tobacco smoke, microbial allergens, oxidants, airborne particulate matter, diesel exhaust particles, polycyclic aromatic hydrocarbons, dietary methyl donors and other nutritional factors, and dust mites is discussed. Exciting findings have been generated by rapid technological advances and well-designed experimental and population studies. The discovery and validation of epigenetic biomarkers linked to exposure, asthma, or both might lead to better epigenotyping of risk, prognosis, treatment prediction, and development of novel therapies. (J Allergy Clin Immunol 2010;126:453-65.). pulmonary disorder| traffic-related pollutants| polycyclic aromatic hydrocarbons| microbial and viral infection| lipopoly-saccharide| endotoxin| oxidant early-life programming| nutrition| maternal exposure| t-h cells| dendritic cells| macrophages| lung epithelial cells| phenotype plasticity| developmental basis of disease| gene-environment interaction| dna methylation| histone modification| microrna| chromatin remodeling| allergen| inflammatory response|adult lung-function| regulatory t-cells| mammalian dna methyltransferases| diesel exhaust particles| tobacco-smoke exposure| early-childhood asthma| breast-cancer cells| ifn-gamma gene| air-pollution| dendritic cells.	SEP-2010	pulmonary disorder| traffic-related pollutants| polycyclic aromatic hydrocarbons| microbial and viral infection| lipopoly-saccharide| endotoxin| oxidant early-life programming| nutrition| maternal exposure| t-h cells| dendritic cells| macrophages| lung epithelial cells| phenotype plasticity| developmental basis of disease| gene-environment interaction| dna methylation| histone modification| microrna| chromatin remodeling| allergen| inflammatory response|adult lung-function| regulatory t-cells| mammalian dna methyltransferases| diesel exhaust particles| tobacco-smoke exposure| early-childhood asthma| breast-cancer cells| ifn-gamma gene| air-pollution| dendritic cells	Ho, SM	Environmental epigenetics of asthma: An update		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Pulmonary disorder; traffic-related pollutants; polycyclic aromatic hydrocarbons; microbial and viral infection; lipopoly-saccharide; endotoxin; oxidant early-life programming; nutrition; maternal exposure; T-H cells; dendritic cells; macrophages; lung epithelial cells; phenotype plasticity; developmental basis of disease; gene-environment interaction; DNA methylation; histone modification; microRNA; chromatin remodeling; allergen; inflammatory response	ADULT LUNG-FUNCTION; REGULATORY T-CELLS; MAMMALIAN DNA METHYLTRANSFERASES; DIESEL EXHAUST PARTICLES; TOBACCO-SMOKE EXPOSURE; EARLY-CHILDHOOD ASTHMA; BREAST-CANCER CELLS; IFN-GAMMA GENE; AIR-POLLUTION; DENDRITIC CELLS	Asthma, a chronic inflammatory disorder of the airway, is influenced by interplay between genetic and environmental factors now known to be mediated by epigenetics. Aberrant DNA methylation, altered histone modifications, specific microRNA expression, and other chromatin alterations orchestrate a complex early-life reprogramming of immune T-cell response, dendritic cell function, macrophage activation, and a breach of airway epithelial barrier that dictates asthma risk and severity in later life. Adult-onset asthma is under analogous regulation. The sharp increase in asthma prevalence over the past 2 or 3 decades and the large variations among populations of similar racial/ethnic background but different environmental exposures favors a strong contribution of environmental factors. This review addresses the fundamental question of whether environmental influences on asthma risk, severity, and steroid resistance are partly due to differential epigenetic modulations. Current knowledge on the epigenetic effects of tobacco smoke, microbial allergens, oxidants, airborne particulate matter, diesel exhaust particles, polycyclic aromatic hydrocarbons, dietary methyl donors and other nutritional factors, and dust mites is discussed. Exciting findings have been generated by rapid technological advances and well-designed experimental and population studies. The discovery and validation of epigenetic biomarkers linked to exposure, asthma, or both might lead to better epigenotyping of risk, prognosis, treatment prediction, and development of novel therapies. (J Allergy Clin Immunol 2010;126:453-65.)	176	95	2010	13	10.1016/j.jaci.2010.07.030	Allergy; Immunology
Population-based cases control study of inflammatory bowel disease risk factors. Background and Aim: The rapid increase in inflammatory bowel disease (IBD) incidence confirms the importance of environment in its etiology. We aimed to assess the role of childhood and other environmental risk factors in IBD. Methods: A population-based case-control study was carried out in Canterbury, New Zealand. Participants comprised 638 prevalent Crohn's disease (CD) cases, 653 prevalent ulcerative colitis (UC) cases and 600 randomly-selected sex and age matched controls. Exposure rates to environmental risk factors were compared. Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CI) are presented. Results: A family history of IBD (CD OR 3.06 [2.18-4.30], UC OR 2.52 [1.90-3.54]), cigarette smoking at diagnosis (CD OR 1.99 [1.48-2.68], UC OR 0.67 [0.48-0.94]), high social class at birth (CD and UC trend, P < 0.001) and Caucasian ethnicity (CD OR 2.04 [1.05-4.38], UC OR 1.47 [1.01-2.14]) were significantly associated with IBD. City living was associated with CD (P < 0.01). Being a migrant was associated with UC (UC OR 1.40 [1.14-2.01]). Having a childhood vegetable garden was protective against IBD (CD OR 0.52 [0.36-0.76], UC OR 0.65 [0.45-0.94]) as was having been breast-fed (CD OR 0.55 [0.41-0.74], UC OR 0.71 [0.52-0.96]) with a duration-response effect. Appendicectomy, tonsillectomy, infectious monomucleosis and asthma were more common in CD patients than controls (P < 0.01). Conclusions: The importance of childhood factors in the development of IBD is confirmed. The duration-response protective association between breast-feeding and subsequent development of IBD requires further evaluation, as does the protective effect associated with a childhood vegetable garden.. crohn's disease| epidemiology| inflammatory bowel diseases| risk factors| ulcerative colitis|onset crohns-disease| ulcerative-colitis| intestinal microflora| childhood exposure| hygiene hypothesis| chinese population| passive smoking| tobacco-smoke| new-zealand| susceptibility.	FEB-2010	crohn's disease| epidemiology| inflammatory bowel diseases| risk factors| ulcerative colitis|onset crohns-disease| ulcerative-colitis| intestinal microflora| childhood exposure| hygiene hypothesis| chinese population| passive smoking| tobacco-smoke| new-zealand| susceptibility	Gearry, RB; Richardson, AK; Frampton, CM; Dodgshun, AJ; Barclay, ML	Population-based cases control study of inflammatory bowel disease risk factors		JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY	Crohn's disease; epidemiology; inflammatory bowel diseases; risk factors; ulcerative colitis	ONSET CROHNS-DISEASE; ULCERATIVE-COLITIS; INTESTINAL MICROFLORA; CHILDHOOD EXPOSURE; HYGIENE HYPOTHESIS; CHINESE POPULATION; PASSIVE SMOKING; TOBACCO-SMOKE; NEW-ZEALAND; SUSCEPTIBILITY	Background and Aim: The rapid increase in inflammatory bowel disease (IBD) incidence confirms the importance of environment in its etiology. We aimed to assess the role of childhood and other environmental risk factors in IBD. Methods: A population-based case-control study was carried out in Canterbury, New Zealand. Participants comprised 638 prevalent Crohn's disease (CD) cases, 653 prevalent ulcerative colitis (UC) cases and 600 randomly-selected sex and age matched controls. Exposure rates to environmental risk factors were compared. Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CI) are presented. Results: A family history of IBD (CD OR 3.06 [2.18-4.30], UC OR 2.52 [1.90-3.54]), cigarette smoking at diagnosis (CD OR 1.99 [1.48-2.68], UC OR 0.67 [0.48-0.94]), high social class at birth (CD and UC trend, P < 0.001) and Caucasian ethnicity (CD OR 2.04 [1.05-4.38], UC OR 1.47 [1.01-2.14]) were significantly associated with IBD. City living was associated with CD (P < 0.01). Being a migrant was associated with UC (UC OR 1.40 [1.14-2.01]). Having a childhood vegetable garden was protective against IBD (CD OR 0.52 [0.36-0.76], UC OR 0.65 [0.45-0.94]) as was having been breast-fed (CD OR 0.55 [0.41-0.74], UC OR 0.71 [0.52-0.96]) with a duration-response effect. Appendicectomy, tonsillectomy, infectious monomucleosis and asthma were more common in CD patients than controls (P < 0.01). Conclusions: The importance of childhood factors in the development of IBD is confirmed. The duration-response protective association between breast-feeding and subsequent development of IBD requires further evaluation, as does the protective effect associated with a childhood vegetable garden.	55	95	2010	9	10.1111/j.1440-1746.2009.06140.x	Gastroenterology & Hepatology
Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways. Background: Exposure to fine ambient particulate matter (PM) has consistently been associated with increased morbidity and mortality. The relationship between exposure to ultrafine particles (UFP) and health effects is less firmly established. If UFP cause health effects independently from coarser fractions, this could affect health impact assessment of air pollution, which would possibly lead to alternative policy options to be considered to reduce the disease burden of PM. Therefore, we organized an expert elicitation workshop to assess the evidence for a causal relationship between exposure to UFP and health endpoints. Methods: An expert elicitation on the health effects of ambient ultrafine particle exposure was carried out, focusing on: 1) the likelihood of causal relationships with key health endpoints, and 2) the likelihood of potential causal pathways for cardiac events. Based on a systematic peernomination procedure, fourteen European experts (epidemiologists, toxicologists and clinicians) were selected, of whom twelve attended. They were provided with a briefing book containing key literature. After a group discussion, individual expert judgments in the form of ratings of the likelihood of causal relationships and pathways were obtained using a confidence scheme adapted from the one used by the Intergovernmental Panel on Climate Change. Results: The likelihood of an independent causal relationship between increased short-term UFP exposure and increased all-cause mortality, hospital admissions for cardiovascular and respiratory diseases, aggravation of asthma symptoms and lung function decrements was rated medium to high by most experts. The likelihood for long-term UFP exposure to be causally related to all cause mortality, cardiovascular and respiratory morbidity and lung cancer was rated slightly lower, mostly medium. The experts rated the likelihood of each of the six identified possible causal pathways separately. Out of these six, the highest likelihood was rated for the pathway involving respiratory inflammation and subsequent thrombotic effects. Conclusion: The overall medium to high likelihood rating of causality of health effects of UFP exposure and the high likelihood rating of at least one of the proposed causal mechanisms explaining associations between UFP and cardiac events, stresses the importance of considering UFP in future health impact assessments of (transport-related) air pollution, and the need for further research on UFP exposure and health effects.. particulate air-pollution| coronary-heart-disease| diesel-exhaust inhalation| long-term exposure| urban air| cardiopulmonary mortality| ambient fine| nanoparticles| association| asthma.	JUL 24-2009	particulate air-pollution| coronary-heart-disease| diesel-exhaust inhalation| long-term exposure| urban air| cardiopulmonary mortality| ambient fine| nanoparticles| association| asthma	Knol, AB; de Hartog, JJ; Boogaard, H; Slottje, P; van der Sluijs, JP; Lebret, E; Cassee, FR; Wardekker, A; Ayres, JG; Borm, PJ; Brunekreef, B; Donaldson, K; Forastiere, F; Holgate, ST; Kreyling, WG; Nemery, B; Pekkanen, J; Stone, V; Wichmann, HE; Hoek, G	Expert elicitation on ultrafine particles: likelihood of health effects and causal pathways		PARTICLE AND FIBRE TOXICOLOGY		PARTICULATE AIR-POLLUTION; CORONARY-HEART-DISEASE; DIESEL-EXHAUST INHALATION; LONG-TERM EXPOSURE; URBAN AIR; CARDIOPULMONARY MORTALITY; AMBIENT FINE; NANOPARTICLES; ASSOCIATION; ASTHMA	Background: Exposure to fine ambient particulate matter (PM) has consistently been associated with increased morbidity and mortality. The relationship between exposure to ultrafine particles (UFP) and health effects is less firmly established. If UFP cause health effects independently from coarser fractions, this could affect health impact assessment of air pollution, which would possibly lead to alternative policy options to be considered to reduce the disease burden of PM. Therefore, we organized an expert elicitation workshop to assess the evidence for a causal relationship between exposure to UFP and health endpoints. Methods: An expert elicitation on the health effects of ambient ultrafine particle exposure was carried out, focusing on: 1) the likelihood of causal relationships with key health endpoints, and 2) the likelihood of potential causal pathways for cardiac events. Based on a systematic peernomination procedure, fourteen European experts (epidemiologists, toxicologists and clinicians) were selected, of whom twelve attended. They were provided with a briefing book containing key literature. After a group discussion, individual expert judgments in the form of ratings of the likelihood of causal relationships and pathways were obtained using a confidence scheme adapted from the one used by the Intergovernmental Panel on Climate Change. Results: The likelihood of an independent causal relationship between increased short-term UFP exposure and increased all-cause mortality, hospital admissions for cardiovascular and respiratory diseases, aggravation of asthma symptoms and lung function decrements was rated medium to high by most experts. The likelihood for long-term UFP exposure to be causally related to all cause mortality, cardiovascular and respiratory morbidity and lung cancer was rated slightly lower, mostly medium. The experts rated the likelihood of each of the six identified possible causal pathways separately. Out of these six, the highest likelihood was rated for the pathway involving respiratory inflammation and subsequent thrombotic effects. Conclusion: The overall medium to high likelihood rating of causality of health effects of UFP exposure and the high likelihood rating of at least one of the proposed causal mechanisms explaining associations between UFP and cardiac events, stresses the importance of considering UFP in future health impact assessments of (transport-related) air pollution, and the need for further research on UFP exposure and health effects.	57	95	2009	16	10.1186/1743-8977-6-19	Toxicology
"Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility. Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control ""Inert"" titanium dioxide (TiO2) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice (or nonpregnant controls) received particle suspensions intranasally at Day 14 of pregnancy. Lung inflammatory responses were evaluated 48 hours after exposure. Offspring of particle- or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Nonpregnant females had the expected minimal response to ""inert"" TiO2. In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO2 and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO2 center dot Neonates of mothers exposed to TiO2 (and DEP, but not PBS) developed AHR and All, indicating that pregnancy exposure to both ""inert"" TiO2 and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles can cause increased allergic susceptibility in offspring.. maternal asthma| environmental particles| titanuim dioxide| diesel exhaust particles| susceptibility|steroid sex-hormones| allergic airway inflammation| diesel exhaust| maternal transmission| alveolar macrophages| langerhans cells| dendritic cells| murine model| mice| risk."	JAN-2008	maternal asthma| environmental particles| titanuim dioxide| diesel exhaust particles| susceptibility|steroid sex-hormones| allergic airway inflammation| diesel exhaust| maternal transmission| alveolar macrophages| langerhans cells| dendritic cells| murine model| mice| risk	Fedulov, AV; Leme, A; Yang, Z; Dahl, M; Lim, R; Mariani, TJ; Kobzik, L	Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	maternal asthma; environmental particles; titanuim dioxide; diesel exhaust particles; susceptibility	STEROID SEX-HORMONES; ALLERGIC AIRWAY INFLAMMATION; DIESEL EXHAUST; MATERNAL TRANSMISSION; ALVEOLAR MACROPHAGES; LANGERHANS CELLS; DENDRITIC CELLS; MURINE MODEL; MICE; RISK	"Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control ""Inert"" titanium dioxide (TiO2) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice (or nonpregnant controls) received particle suspensions intranasally at Day 14 of pregnancy. Lung inflammatory responses were evaluated 48 hours after exposure. Offspring of particle- or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Nonpregnant females had the expected minimal response to ""inert"" TiO2. In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO2 and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO2 center dot Neonates of mothers exposed to TiO2 (and DEP, but not PBS) developed AHR and All, indicating that pregnancy exposure to both ""inert"" TiO2 and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles can cause increased allergic susceptibility in offspring."	53	95	2008	11	10.1165/rcmb.2007-0124OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Airway hyperresponsiveness in allergically inflamed mice - The role of airway closure. Rationale: Allergically inflamed mice exhibit airway hyper-responsiveness to inhaled methacholine, which computer simulations of lung impedance suggest is due to enhanced lung derecruitment and which we sought to verify in the present study. Methods: BALB/c mice were sensitized and challenged with ovalbumin to induce allergic inflammation; the control mice were sensitized but received no challenge. The mice were then challenged with inhaled methacholine and respiratory system impedance tracked for the following 10 minutes. Respiratory elastance (H) was estimated from each impedance measurement. One group of mice was ventilated with 100% O-2 during this procedure and another group was ventilated with air. After the procedure, the mice were killed and ventilated with pure N-2, after which the trachea was tied off and the lungs were imaged with micro-computed tomography (micro-CT). Results: H was significantly higher in allergic mice than in control animals after methacholine challenge. The ratio of H at the end of the measurement period between allergic and nonallergic mice ventilated with O-2 was 1.36, indicating substantial derecruitment in the allergic animals. The ratio between lung volumes determined by micro-CT in the control and the allergic mice was also 1.36, indicative of a corresponding volume loss due to absorption atelectasis. Micro-CT images and histograms of Hounsfield units from the lungs also showed increased volume loss in the allergic mice compared with control animals after methacholine challenge. Conclusions: These results support the conclusion that airway closure is a major component of hyperresponsiveness in allergically inflamed mice.. asthma| micro-computed tomography| input impedance| lung derecruitment| lung volume|smooth-muscle contraction| temporal dynamics| asthma| lung| dogs| hyperoxia| rat| bronchoconstriction| ventilation| challenge.	APR 15-2007	asthma| micro-computed tomography| input impedance| lung derecruitment| lung volume|smooth-muscle contraction| temporal dynamics| asthma| lung| dogs| hyperoxia| rat| bronchoconstriction| ventilation| challenge	Lundblad, LKA; Thompson-Figueroa, J; Allen, GB; Rinaldi, L; Norton, RJ; Irvin, CG; Bates, JHT	Airway hyperresponsiveness in allergically inflamed mice - The role of airway closure		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; micro-computed tomography; input impedance; lung derecruitment; lung volume	SMOOTH-MUSCLE CONTRACTION; TEMPORAL DYNAMICS; ASTHMA; LUNG; DOGS; HYPEROXIA; RAT; BRONCHOCONSTRICTION; VENTILATION; CHALLENGE	Rationale: Allergically inflamed mice exhibit airway hyper-responsiveness to inhaled methacholine, which computer simulations of lung impedance suggest is due to enhanced lung derecruitment and which we sought to verify in the present study. Methods: BALB/c mice were sensitized and challenged with ovalbumin to induce allergic inflammation; the control mice were sensitized but received no challenge. The mice were then challenged with inhaled methacholine and respiratory system impedance tracked for the following 10 minutes. Respiratory elastance (H) was estimated from each impedance measurement. One group of mice was ventilated with 100% O-2 during this procedure and another group was ventilated with air. After the procedure, the mice were killed and ventilated with pure N-2, after which the trachea was tied off and the lungs were imaged with micro-computed tomography (micro-CT). Results: H was significantly higher in allergic mice than in control animals after methacholine challenge. The ratio of H at the end of the measurement period between allergic and nonallergic mice ventilated with O-2 was 1.36, indicating substantial derecruitment in the allergic animals. The ratio between lung volumes determined by micro-CT in the control and the allergic mice was also 1.36, indicative of a corresponding volume loss due to absorption atelectasis. Micro-CT images and histograms of Hounsfield units from the lungs also showed increased volume loss in the allergic mice compared with control animals after methacholine challenge. Conclusions: These results support the conclusion that airway closure is a major component of hyperresponsiveness in allergically inflamed mice.	29	95	2007	7	10.1164/rccm.200610-1410OC	General & Internal Medicine; Respiratory System
The house dust mite allergen Der p 1, unlike Der p 3, stimulates the expression of interleukin-8 in human airway epithelial cells via a proteinase-activated receptor-2-independent mechanism. We investigated and compared the mechanisms by which two dust mite proteolytic allergens, Der p 1 and Der p 3, and a peptide agonist of proteinase-activated receptor 2 (PAR(2)AP) trigger interleukin (IL)-8 release from human pulmonary epithelial cells (A549). Although all three stimuli tested induced the up-regulation of IL-8 ( mRNA and protein), the Der p 1-mediated signaling events did not exactly match those induced by PAR(2)AP and Der p 3. First, Der p 1 was less effective in stimulating IL-8 gene transcriptional activity than PAR(2)AP and Der p 3. Second, Der p 1-mediated IL-8 expression was mainly dependent on NF-kappa B, whereas Der p 3 and PAR(2)AP regulated IL-8 expression through the activation of both NF-kappa B and AP-1. Third, although all three MAP kinases, ERK1/2, p38, and JNK, were activated, Der p 1 induced IL-8 release exclusively via the ERK1/2 signaling pathway, whereas PAR(2)AP and Der p 3 also involved the other kinases. Fourth, in HeLa cells, Der p 1 was able to up-regulate IL-8 secretion independent of PAR(2) expression, and in contrast with PAR(2)AP and Der p 3, Der p 1 was unable to affect calcium signaling via PAR(2) in PAR(2)-expressing KNRK cells. Finally, cleavage by Der p 1 of a synthetic peptide representing the N-terminal activation-cleavage site of PAR(2) did not release a high potency activator of PAR(2) as does Der p 3. We conclude that Der p 1 ( but not Der p 3)-induced IL-8 production in A549 epithelial cells is independent of PAR(2) activation.. nf-kappa-b| tumor-necrosis-factor| cysteine protease activity| induce cytokine release| transcription factors| gene-expression| inflammatory cytokines| tight junctions| gm-csf| receptor-2.	MAR 17-2006	nf-kappa-b| tumor-necrosis-factor| cysteine protease activity| induce cytokine release| transcription factors| gene-expression| inflammatory cytokines| tight junctions| gm-csf| receptor-2	Adam, E; Hansen, KK; Astudillo, OF; Coulon, L; Bex, F; Duhant, X; Jaumotte, E; Hollenberg, MD; Jacquet, A	The house dust mite allergen Der p 1, unlike Der p 3, stimulates the expression of interleukin-8 in human airway epithelial cells via a proteinase-activated receptor-2-independent mechanism		JOURNAL OF BIOLOGICAL CHEMISTRY		NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; CYSTEINE PROTEASE ACTIVITY; INDUCE CYTOKINE RELEASE; TRANSCRIPTION FACTORS; GENE-EXPRESSION; INFLAMMATORY CYTOKINES; TIGHT JUNCTIONS; GM-CSF; RECEPTOR-2	We investigated and compared the mechanisms by which two dust mite proteolytic allergens, Der p 1 and Der p 3, and a peptide agonist of proteinase-activated receptor 2 (PAR(2)AP) trigger interleukin (IL)-8 release from human pulmonary epithelial cells (A549). Although all three stimuli tested induced the up-regulation of IL-8 ( mRNA and protein), the Der p 1-mediated signaling events did not exactly match those induced by PAR(2)AP and Der p 3. First, Der p 1 was less effective in stimulating IL-8 gene transcriptional activity than PAR(2)AP and Der p 3. Second, Der p 1-mediated IL-8 expression was mainly dependent on NF-kappa B, whereas Der p 3 and PAR(2)AP regulated IL-8 expression through the activation of both NF-kappa B and AP-1. Third, although all three MAP kinases, ERK1/2, p38, and JNK, were activated, Der p 1 induced IL-8 release exclusively via the ERK1/2 signaling pathway, whereas PAR(2)AP and Der p 3 also involved the other kinases. Fourth, in HeLa cells, Der p 1 was able to up-regulate IL-8 secretion independent of PAR(2) expression, and in contrast with PAR(2)AP and Der p 3, Der p 1 was unable to affect calcium signaling via PAR(2) in PAR(2)-expressing KNRK cells. Finally, cleavage by Der p 1 of a synthetic peptide representing the N-terminal activation-cleavage site of PAR(2) did not release a high potency activator of PAR(2) as does Der p 3. We conclude that Der p 1 ( but not Der p 3)-induced IL-8 production in A549 epithelial cells is independent of PAR(2) activation.	67	95	2006	14	10.1074/jbc.M507140200	Biochemistry & Molecular Biology
Physical activity and exercise in asthma: Relevance to etiology and treatment. There is little doubt that the cause of the increased prevalence and severity of asthma is multifactorial. Although the factors of allergen exposure and hygiene are almost certainly necessary for its development, there is a growing body of literature that implicates lifestyle change, specifically decreased physical activity, as a contributor to the increase in asthma prevalence and severity. Several literature reviews of exercise conditioning in patients with asthma have been published. These reviews and recent controlled trials emphasize that although many of the studies of exercise conditioning in asthmatic patients involved different methods and outcome measures, the overwhelming majority of studies demonstrated the capacity for asthmatic subjects to exercise safely and significantly improve their cardiovascular fitness and quality of life. There are several proposed pathophysiologic mechanisms responsible for the effects of decreased activity on the lung function of patients with asthma. A prescription for exercise has been endorsed for all asthmatic subjects by the American College of Sports Medicine and the American Thoracic Society. The allergy community has placed emphasis on medical therapy and allergen avoidance; in addition, exercise avoidance has not been formally incorporated into the National Asthma Education and Prevention Program guidelines. It is our belief that an exercise prescription should be part of the treatment for all cases of asthma. The real question is whether prolonged physical activity and, in particular, outdoor play of children plays a role in prophylaxis against persistent wheezing. If so, the decrease in physical activity might have played a major role in recent increases in asthma prevalence and severity.. asthma exercise| conditioning| etiology| pathophysiology| sedentary lifestyle| activity| therapy| incidence| severity|airway smooth-muscle| deep inspiration| children| program| obesity| hyperresponsiveness| overweight| intensity| risk.	MAY-2005	asthma exercise| conditioning| etiology| pathophysiology| sedentary lifestyle| activity| therapy| incidence| severity|airway smooth-muscle| deep inspiration| children| program| obesity| hyperresponsiveness| overweight| intensity| risk	Lucas, SR; Platts-Mills, TAE	Physical activity and exercise in asthma: Relevance to etiology and treatment		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma exercise; conditioning; etiology; pathophysiology; sedentary lifestyle; activity; therapy; incidence; severity	AIRWAY SMOOTH-MUSCLE; DEEP INSPIRATION; CHILDREN; PROGRAM; OBESITY; HYPERRESPONSIVENESS; OVERWEIGHT; INTENSITY; RISK	There is little doubt that the cause of the increased prevalence and severity of asthma is multifactorial. Although the factors of allergen exposure and hygiene are almost certainly necessary for its development, there is a growing body of literature that implicates lifestyle change, specifically decreased physical activity, as a contributor to the increase in asthma prevalence and severity. Several literature reviews of exercise conditioning in patients with asthma have been published. These reviews and recent controlled trials emphasize that although many of the studies of exercise conditioning in asthmatic patients involved different methods and outcome measures, the overwhelming majority of studies demonstrated the capacity for asthmatic subjects to exercise safely and significantly improve their cardiovascular fitness and quality of life. There are several proposed pathophysiologic mechanisms responsible for the effects of decreased activity on the lung function of patients with asthma. A prescription for exercise has been endorsed for all asthmatic subjects by the American College of Sports Medicine and the American Thoracic Society. The allergy community has placed emphasis on medical therapy and allergen avoidance; in addition, exercise avoidance has not been formally incorporated into the National Asthma Education and Prevention Program guidelines. It is our belief that an exercise prescription should be part of the treatment for all cases of asthma. The real question is whether prolonged physical activity and, in particular, outdoor play of children plays a role in prophylaxis against persistent wheezing. If so, the decrease in physical activity might have played a major role in recent increases in asthma prevalence and severity.	44	95	2005	7	10.1016/j.jaci.2005.01.033	Allergy; Immunology
Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment. Background: Airway dendritic cells (DCs) are crucial for allergen-induced sensitization and inflammation in allergic asthma. After allergen challenge, an increased number of DCs is observed in airway epithelium from patients with allergy. Objective: Because Der p 1, a cysteine protease allergen from Dermatophagoides pteronyssinus, induces chemokine production by bronchial epithelial cells (BECs), the purpose of this investigation was to evaluate the capacity of BEC exposed to Der p 1 to recruit DCs. Methods: Chemotactic activity of BEAS-2B, a bronchial epithelial cell line, and BECs from nonatopic controls and patients with allergic asthma was evaluated on the migration of precursors, immature and mature monocyte-derived DCs (MDDCs), and CD34(+)-derived Langerhans cells (LCs). Results: C-C chemokine ligand (CCL)-2, CCL5, and C-X-C chemokine ligand 10 production by BEAS-2B and BEC was increased after Der p 1 exposure, whereas the proenzyme proDer p 1 devoid of enzymatic activity had no effect. Der p I stimulation of BEAS-2B and BEC from both groups increased significantly the recruitment of MDDC precursors, depending on CCL2, CCL5, and C-X-C chemokine ligand 10 production. In a reconstituted polarized epithelium, apical application of Der p I enhanced MDDC precursor migration into the epithelial layer. Moreover, Der p 1 stimulation of BEC from patients with asthma but not from controls increased the migration of LC precursors, mainly dependent on CCL20 secretion. No migration of immature and mature DCs was observed. Conclusion: These data confirmed that BECs participate in the homeostasis of the DC network present within the bronchial epithelium through the secretion of chemokines. In allergic asthma, upregulation of CCL20 production induced LC recruitment, the role of which remains to be determined.. epithelial cells| dendritic cells| chemokines| allergy| lung|inflammatory protein 3-alpha| bronchoalveolar lavage fluid| necrosis-factor-alpha| atopic asthma| proinflammatory cytokines| intestinal epithelium| respiratory-tract| airway epithelium| anatomic sites| up-regulation.	APR-2005	epithelial cells| dendritic cells| chemokines| allergy| lung|inflammatory protein 3-alpha| bronchoalveolar lavage fluid| necrosis-factor-alpha| atopic asthma| proinflammatory cytokines| intestinal epithelium| respiratory-tract| airway epithelium| anatomic sites| up-regulation	Pichavant, M; Charbonnier, AS; Taront, S; Brichet, AB; Wallaert, B; Pestel, J; Tonnel, AB; Gosset, P	Asthmatic bronchial epithelium activated by the proteolytic allergen Der p 1 increases selective dendritic cell recruitment		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	epithelial cells; dendritic cells; chemokines; allergy; lung	INFLAMMATORY PROTEIN 3-ALPHA; BRONCHOALVEOLAR LAVAGE FLUID; NECROSIS-FACTOR-ALPHA; ATOPIC ASTHMA; PROINFLAMMATORY CYTOKINES; INTESTINAL EPITHELIUM; RESPIRATORY-TRACT; AIRWAY EPITHELIUM; ANATOMIC SITES; UP-REGULATION	Background: Airway dendritic cells (DCs) are crucial for allergen-induced sensitization and inflammation in allergic asthma. After allergen challenge, an increased number of DCs is observed in airway epithelium from patients with allergy. Objective: Because Der p 1, a cysteine protease allergen from Dermatophagoides pteronyssinus, induces chemokine production by bronchial epithelial cells (BECs), the purpose of this investigation was to evaluate the capacity of BEC exposed to Der p 1 to recruit DCs. Methods: Chemotactic activity of BEAS-2B, a bronchial epithelial cell line, and BECs from nonatopic controls and patients with allergic asthma was evaluated on the migration of precursors, immature and mature monocyte-derived DCs (MDDCs), and CD34(+)-derived Langerhans cells (LCs). Results: C-C chemokine ligand (CCL)-2, CCL5, and C-X-C chemokine ligand 10 production by BEAS-2B and BEC was increased after Der p 1 exposure, whereas the proenzyme proDer p 1 devoid of enzymatic activity had no effect. Der p I stimulation of BEAS-2B and BEC from both groups increased significantly the recruitment of MDDC precursors, depending on CCL2, CCL5, and C-X-C chemokine ligand 10 production. In a reconstituted polarized epithelium, apical application of Der p I enhanced MDDC precursor migration into the epithelial layer. Moreover, Der p 1 stimulation of BEC from patients with asthma but not from controls increased the migration of LC precursors, mainly dependent on CCL20 secretion. No migration of immature and mature DCs was observed. Conclusion: These data confirmed that BECs participate in the homeostasis of the DC network present within the bronchial epithelium through the secretion of chemokines. In allergic asthma, upregulation of CCL20 production induced LC recruitment, the role of which remains to be determined.	42	95	2005	8	10.1016/j.jaci.2004.11.043	Allergy; Immunology
Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study. Background: For many years it has been assumed that the risk of childhood respiratory allergies is related to allergen exposures in early life. There are, however, few prospective data in support. We aimed to examine this relationship in a representative cohort of children born in Ashford, Kent (UK). Methods: 625 children (94% of those eligible) were followed from birth to the age of 5.5 years at which time 552 underwent skin prick testing to extracts of house dust mite and cat fur allergens. Maternal reports of wheeze in the last year were collected by interview. These outcomes were related to individual domestic concentrations of Der p 1 and Fel d I allergens estimated from dust collection at the age of 8 weeks. Results: 10% of children were sensitised to house dust mite or cat at age 5.5 years; 7% had atopic wheeze. No significant relationships between allergen exposure and either sensitisation or wheeze were found but, on examination, the exposure-response relationships for both allergens and for each outcome rose steeply at low levels of exposure and were attenuated at high levels of exposure. These patterns were modified by paternal atopy and by birth order. Conclusions: There are no linear relationships between early allergen exposure and the induction of childhood respiratory allergy; rather, the risks of IgE sensitisation and asthma rise at very low levels of exposure and are attenuated thereafter. These patterns are influenced by parental atopy and birth order. These findings suggest important gene-environment interactions in the development of atopy and asthma and imply that reductions in domestic allergen exposure alone are unlikely to have a major impact in decreasing the incidence of these diseases in childhood.. house-dust mite| asthma| sensitization| childhood| environment| risk.	OCT-2004	house-dust mite| asthma| sensitization| childhood| environment| risk	Cullinan, P; MacNeill, SJ; Harris, JM; Moffat, S; White, C; Mills, P; Taylor, AJN	Early allergen exposure, skin prick responses, and atopic wheeze at age 5 in English children: a cohort study		THORAX		HOUSE-DUST MITE; ASTHMA; SENSITIZATION; CHILDHOOD; ENVIRONMENT; RISK	Background: For many years it has been assumed that the risk of childhood respiratory allergies is related to allergen exposures in early life. There are, however, few prospective data in support. We aimed to examine this relationship in a representative cohort of children born in Ashford, Kent (UK). Methods: 625 children (94% of those eligible) were followed from birth to the age of 5.5 years at which time 552 underwent skin prick testing to extracts of house dust mite and cat fur allergens. Maternal reports of wheeze in the last year were collected by interview. These outcomes were related to individual domestic concentrations of Der p 1 and Fel d I allergens estimated from dust collection at the age of 8 weeks. Results: 10% of children were sensitised to house dust mite or cat at age 5.5 years; 7% had atopic wheeze. No significant relationships between allergen exposure and either sensitisation or wheeze were found but, on examination, the exposure-response relationships for both allergens and for each outcome rose steeply at low levels of exposure and were attenuated at high levels of exposure. These patterns were modified by paternal atopy and by birth order. Conclusions: There are no linear relationships between early allergen exposure and the induction of childhood respiratory allergy; rather, the risks of IgE sensitisation and asthma rise at very low levels of exposure and are attenuated thereafter. These patterns are influenced by parental atopy and birth order. These findings suggest important gene-environment interactions in the development of atopy and asthma and imply that reductions in domestic allergen exposure alone are unlikely to have a major impact in decreasing the incidence of these diseases in childhood.	15	95	2004	7	10.1136/thx.2003.019877	Respiratory System
Structural model of MD-2 and functional role of its basic amino acid clusters involved in cellular lipopolysaccharide recognition. The receptor complex resulting from association of MD-2 and the ectodomain of Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signal transduction across the cell membrane. We prepared a tertiary structure model of MD-2, based on the known structures of homologous lipid-binding proteins. Analysis of circular dichroic spectra of purified bacterially expressed MD-2 indicates high content of beta-type secondary structure, in agreement with the structural model. Bacterially expressed MD-2 was able to confer LPS responsiveness to cells expressing TLR4 despite lacking glycosylation. We identified several clusters of basic residues on the surface of MD-2. Mutation of each of two clusters encompassing the residues Lys(89)-Arg(90)-Lys(91) and Lys(125)-Lys(125) significantly decreased the signal transduction of the respective MD-2 mutants either upon co-expression with TLR4 or upon addition as soluble protein into the supernatant of cells overexpressing TLR4. These basic clusters lie at the edge of the beta-sheet sandwich, which in cholesterol-binding protein connected to Niemann-Pick disease C2 (NPC2), dust mite allergen Der p2, and ganglioside GM2-activator protein form a hydrophobic pocket. In contrast, mutation of another basic cluster composed of Arg(69)-Lys(72), which according to the model lies further apart from the hydrophobic pocket only weakly decreased MD-2 activity. Furthermore, addition of the peptide, comprising the surface loop between Cys(95) and Cys(105), predicted by model, particularly in oxidized form, decreased LPS-induced production of tumor necrosis factor alpha and interleukin-8 upon application to monocytic cells and fibroblasts, respectively, supporting its involvement in LPS signaling. Our structural model of MD-2 is corroborated by biochemical analysis and contributes to the unraveling of molecular interactions in LPS recognition.. toll-like receptor-4| dust-mite allergen| signal-transduction| crystal-structure| gm2-activator protein| tertiary structure| innate immunity| disulfide bonds| responsiveness| complex.	JUL 2-2004	toll-like receptor-4| dust-mite allergen| signal-transduction| crystal-structure| gm2-activator protein| tertiary structure| innate immunity| disulfide bonds| responsiveness| complex	Gruber, A; Mancek, M; Wagner, H; Kirschning, CJ; Jerala, R	Structural model of MD-2 and functional role of its basic amino acid clusters involved in cellular lipopolysaccharide recognition		JOURNAL OF BIOLOGICAL CHEMISTRY		TOLL-LIKE RECEPTOR-4; DUST-MITE ALLERGEN; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; GM2-ACTIVATOR PROTEIN; TERTIARY STRUCTURE; INNATE IMMUNITY; DISULFIDE BONDS; RESPONSIVENESS; COMPLEX	The receptor complex resulting from association of MD-2 and the ectodomain of Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signal transduction across the cell membrane. We prepared a tertiary structure model of MD-2, based on the known structures of homologous lipid-binding proteins. Analysis of circular dichroic spectra of purified bacterially expressed MD-2 indicates high content of beta-type secondary structure, in agreement with the structural model. Bacterially expressed MD-2 was able to confer LPS responsiveness to cells expressing TLR4 despite lacking glycosylation. We identified several clusters of basic residues on the surface of MD-2. Mutation of each of two clusters encompassing the residues Lys(89)-Arg(90)-Lys(91) and Lys(125)-Lys(125) significantly decreased the signal transduction of the respective MD-2 mutants either upon co-expression with TLR4 or upon addition as soluble protein into the supernatant of cells overexpressing TLR4. These basic clusters lie at the edge of the beta-sheet sandwich, which in cholesterol-binding protein connected to Niemann-Pick disease C2 (NPC2), dust mite allergen Der p2, and ganglioside GM2-activator protein form a hydrophobic pocket. In contrast, mutation of another basic cluster composed of Arg(69)-Lys(72), which according to the model lies further apart from the hydrophobic pocket only weakly decreased MD-2 activity. Furthermore, addition of the peptide, comprising the surface loop between Cys(95) and Cys(105), predicted by model, particularly in oxidized form, decreased LPS-induced production of tumor necrosis factor alpha and interleukin-8 upon application to monocytic cells and fibroblasts, respectively, supporting its involvement in LPS signaling. Our structural model of MD-2 is corroborated by biochemical analysis and contributes to the unraveling of molecular interactions in LPS recognition.	47	95	2004	8	10.1074/jbc.M400993200	Biochemistry & Molecular Biology
Asthma, wheezing, and allergies in Russian schoolchildren in relation to new surface materials in the home. In a cross-sectional study of 5951 Russian 8-12-year-old schoolchildren, risks of current asthma, wheezing, and allergy were related to recent renovation and the installation of materials with potential chemical emissions. New linoleum flooring, synthetic carpeting, particleboard, wall coverings, and furniture and recent painting were determinants of 1 or several of these 3 health outcomes. These findings warrant further attention to the type of materials used in interior design.. young-children| symptoms| health.	APR-2004	young-children| symptoms| health	Jaakkola, JJK; Parise, H; Kislitsin, V; Lebedeva, NI; Spengler, JD	Asthma, wheezing, and allergies in Russian schoolchildren in relation to new surface materials in the home		AMERICAN JOURNAL OF PUBLIC HEALTH		YOUNG-CHILDREN; SYMPTOMS; HEALTH	In a cross-sectional study of 5951 Russian 8-12-year-old schoolchildren, risks of current asthma, wheezing, and allergy were related to recent renovation and the installation of materials with potential chemical emissions. New linoleum flooring, synthetic carpeting, particleboard, wall coverings, and furniture and recent painting were determinants of 1 or several of these 3 health outcomes. These findings warrant further attention to the type of materials used in interior design.	9	95	2004	3	10.2105/AJPH.94.4.560	Public, Environmental & Occupational Health
Ambient endotoxin concentrations in PM10 from Southern California. Concentrations of endotoxin in urban air pollution have not previously been extensively characterized. We measured 24-hr levels of PM10 (particulate matter < 10 mum in aerodynamic diameter) and the associated endotoxin component once every 6 weeks for 1 year in 13 communities in Southern California. All the samples collected had detectable PM10 and endotoxin levels. The geometric mean PM10 was 34.6 mug/m(3) [geometric SD (GSD), 2.1; range, 3.0-135]. By volume, the endotoxin geometric mean was 0.44 endotoxin units (EU)/m(3) (GSD, 3.1; range, 0.03-5.44). Per unit material collected, the geometric mean of endotoxin collected was 13.6 EU/mg (GSD, 3.2; range, 0.7-96.8). No correlation was found between endotoxin concentrations and other ambient pollutants concurrently measured [ozone, nitrogen dioxide, total acids, or PM2.5 (particulate matter < 2.5 put in aerodynamic diameter]. PM10 and endotoxin concentrations were significantly correlated, most strongly in summer. Samples collected in more rural and agricultural areas had lower PM10 and mid-range endotoxin levels. The high desert and mountain communities had lower PM10 levels but endotoxin levels comparable with or higher than the rural agricultural sites. By volume, endotoxin levels were highest at sites downwind of Los Angeles, California, which were also the locations of highest PM10. Endotoxin concentrations measured in this study were all < 5.5 EU/m(3), which is lower than recognized thresholds for acute adverse health effects for occupational exposures but in the same range as indoor household concentrations. This study provides the first extensive characterization of endotoxin concentration across a large metropolitan area in relation to PM10 and other pollutant monitoring, and supports the need for studies of the role of endotoxin in childhood asthma in urban settings.. air pollution| bioaerosol| endotoxin| lipopolysaccharide| particulate matter|particulate air-pollution| lung-function growth| alveolar macrophage responses| in-house dust| airborne endotoxin| daily mortality| insoluble components| exposure-response| inhaled endotoxin| coarse particles.	APR-2004	air pollution| bioaerosol| endotoxin| lipopolysaccharide| particulate matter|particulate air-pollution| lung-function growth| alveolar macrophage responses| in-house dust| airborne endotoxin| daily mortality| insoluble components| exposure-response| inhaled endotoxin| coarse particles	Mueller-Anneling, L; Avol, E; Peters, JM; Thorne, PS	Ambient endotoxin concentrations in PM10 from Southern California		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; bioaerosol; endotoxin; lipopolysaccharide; particulate matter	PARTICULATE AIR-POLLUTION; LUNG-FUNCTION GROWTH; ALVEOLAR MACROPHAGE RESPONSES; IN-HOUSE DUST; AIRBORNE ENDOTOXIN; DAILY MORTALITY; INSOLUBLE COMPONENTS; EXPOSURE-RESPONSE; INHALED ENDOTOXIN; COARSE PARTICLES	Concentrations of endotoxin in urban air pollution have not previously been extensively characterized. We measured 24-hr levels of PM10 (particulate matter < 10 mum in aerodynamic diameter) and the associated endotoxin component once every 6 weeks for 1 year in 13 communities in Southern California. All the samples collected had detectable PM10 and endotoxin levels. The geometric mean PM10 was 34.6 mug/m(3) [geometric SD (GSD), 2.1; range, 3.0-135]. By volume, the endotoxin geometric mean was 0.44 endotoxin units (EU)/m(3) (GSD, 3.1; range, 0.03-5.44). Per unit material collected, the geometric mean of endotoxin collected was 13.6 EU/mg (GSD, 3.2; range, 0.7-96.8). No correlation was found between endotoxin concentrations and other ambient pollutants concurrently measured [ozone, nitrogen dioxide, total acids, or PM2.5 (particulate matter < 2.5 put in aerodynamic diameter]. PM10 and endotoxin concentrations were significantly correlated, most strongly in summer. Samples collected in more rural and agricultural areas had lower PM10 and mid-range endotoxin levels. The high desert and mountain communities had lower PM10 levels but endotoxin levels comparable with or higher than the rural agricultural sites. By volume, endotoxin levels were highest at sites downwind of Los Angeles, California, which were also the locations of highest PM10. Endotoxin concentrations measured in this study were all < 5.5 EU/m(3), which is lower than recognized thresholds for acute adverse health effects for occupational exposures but in the same range as indoor household concentrations. This study provides the first extensive characterization of endotoxin concentration across a large metropolitan area in relation to PM10 and other pollutant monitoring, and supports the need for studies of the role of endotoxin in childhood asthma in urban settings.	54	95	2004	6	10.1289/ehp.6552	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Allergen detection from 11 fungal species before and after germination. Background: Allergens dispersed by airborne fungal spores play an important but poorly understood role in the underlying cause and exacerbation of asthma. Previous studies suggest that spores of Alternaria and Aspergillus release greater quantities of allergen after germination than before germination. It is unknown whether this is true of other allergenic fungi. Objective: Our purpose was to investigate the release of allergen from a range of individual fungal-spores before and after germination. Methods: Allergen expression from spores of Alternaria alternata, Cladosporium herbarum, Aspergillius fumigatus, Botrytis cinerea, Epicoccum nigrum, Exserohilum rostralum, Penicillium chrysogenum, Stemphylium botryosum, Curvularia lunata, Trichoderma viride, and Bipolaris spicifera was examined by halogen immunoassays through the use of pooled serum IgE from patients allergic to fungus. Spores were deposited onto proteinbinding membranes direct, from culture. To germinate spores, samples were incubated in high humidity at room temperature for 48 hours. Ungerminated and germinated samples were then laminated with an adhesive film and immunostained by the halogen assay. The samples were examined by light microscopy, and positive counts (haloed particles) were expressed as percentages of total spores. Results: For 9 of 11 species, between 5.7% and 92% of spores released allergen before germination. Spores of Penicillium and Trichodemia did not release detectable allergen. After germination, all spores that germinated had allergen elution from their hyphae. Eight of I I species showed a significant increase (P <.05) in the percentage of spores eluting detectable allergen. Localization of allergen along the hyphae varied with species, such that some eluted allergen mainly from hyphal tips and septal junctions whereas others eluted allergen along the entire length. Conclusions: Increased elution of allergen after germination might be a common feature of many species of allergenic fungi. Although allergens from both spores and hyphae were recognized by human IgE, the extent to which human exposure occurs to allergens eluted from inhaled spores or from hyphae that germinate after deposition in the respiratory tract remains to be explored. The patterns of allergen expression might affect the clinical response to such exposure. (J Allergy Clin Immunol 2003;111:285-9.).. allergen| fungi| germination| halogen| immunoassay|asp-f-i| aspergillus-fumigatus| alternaria-alternata| binding protein| different media| major allergen| ige antibodies| risk factor| expression| asthma.	FEB-2003	allergen| fungi| germination| halogen| immunoassay|asp-f-i| aspergillus-fumigatus| alternaria-alternata| binding protein| different media| major allergen| ige antibodies| risk factor| expression| asthma	Green, BJ; Mitakakis, TZ; Tovey, ER	Allergen detection from 11 fungal species before and after germination		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen; fungi; germination; halogen; immunoassay	ASP-F-I; ASPERGILLUS-FUMIGATUS; ALTERNARIA-ALTERNATA; BINDING PROTEIN; DIFFERENT MEDIA; MAJOR ALLERGEN; IGE ANTIBODIES; RISK FACTOR; EXPRESSION; ASTHMA	Background: Allergens dispersed by airborne fungal spores play an important but poorly understood role in the underlying cause and exacerbation of asthma. Previous studies suggest that spores of Alternaria and Aspergillus release greater quantities of allergen after germination than before germination. It is unknown whether this is true of other allergenic fungi. Objective: Our purpose was to investigate the release of allergen from a range of individual fungal-spores before and after germination. Methods: Allergen expression from spores of Alternaria alternata, Cladosporium herbarum, Aspergillius fumigatus, Botrytis cinerea, Epicoccum nigrum, Exserohilum rostralum, Penicillium chrysogenum, Stemphylium botryosum, Curvularia lunata, Trichoderma viride, and Bipolaris spicifera was examined by halogen immunoassays through the use of pooled serum IgE from patients allergic to fungus. Spores were deposited onto proteinbinding membranes direct, from culture. To germinate spores, samples were incubated in high humidity at room temperature for 48 hours. Ungerminated and germinated samples were then laminated with an adhesive film and immunostained by the halogen assay. The samples were examined by light microscopy, and positive counts (haloed particles) were expressed as percentages of total spores. Results: For 9 of 11 species, between 5.7% and 92% of spores released allergen before germination. Spores of Penicillium and Trichodemia did not release detectable allergen. After germination, all spores that germinated had allergen elution from their hyphae. Eight of I I species showed a significant increase (P <.05) in the percentage of spores eluting detectable allergen. Localization of allergen along the hyphae varied with species, such that some eluted allergen mainly from hyphal tips and septal junctions whereas others eluted allergen along the entire length. Conclusions: Increased elution of allergen after germination might be a common feature of many species of allergenic fungi. Although allergens from both spores and hyphae were recognized by human IgE, the extent to which human exposure occurs to allergens eluted from inhaled spores or from hyphae that germinate after deposition in the respiratory tract remains to be explored. The patterns of allergen expression might affect the clinical response to such exposure. (J Allergy Clin Immunol 2003;111:285-9.).	36	95	2003	5	10.1067/mai.2003.57	Allergy; Immunology
Primary prevention of natural rubber latex allergy in the German health care system through education and intervention. Background: The development of occupational asthma and allergic skin reactions caused by natural rubber latex (NRL) allergy are risks for health care workers. There are few published studies to suggest that intervention programs to reduce exposure will lead to primary prevention of sensitization. Objective: This study assesses the effects of intervention to reduce the incidence of NRL allergy in personnel working in health care facilities insured by the German statutory accident insurance company for health care workers, Berufsgenossenschaft fur Gesundheitsdienst und Wohlfahrtspflege, with approximately 3 million insured employees, by switching to powder-free NRL gloves. Methods: The timing of introduction of intervention strategies, such as education of both physicians and administrators, together with regulations demanding that health care facilities only purchase low-protein, powder-free NRL gloves are reported. We reviewed the annual numbers of reported suspected cases of NRL-caused occupational allergies and the amount and type of gloves used in German acute-care hospitals since 1986. Results: The purchase of powder-free NRL examination gloves exceeded that of powdered gloves for the first time in 1998. This only became true for powder-free NRL sterile gloves 2 years later in 2000. The incidence of suspected occupational NRL allergy cases rose until 1998 and has declined steadily since. There was a 2-year lag between the beginning of the decline in the purchase of powdered NRL examination gloves and the beginning of a decline in suspected NRL-caused occupational asthma cases. Conclusions: Despite the effect of increased recognition of NRL allergies, education about NRL allergies in health care facilities combined with the introduction of powder-free gloves with reduced protein levels has been associated with a decline in the number of suspected cases of occupational allergies caused by NRL in Germany on a nationwide scale. These results clearly indicate that primary prevention of occupational NRL allergies can be achieved if these straightforward and practical interventions are properly carried out and maintained.. occupational asthma| natural rubber latex allergy| powder free latex gloves| latex allergens| primary prevention|ige antibodies| gloves| sensitization| prevalence| workers| nurses.	AUG-2002	occupational asthma| natural rubber latex allergy| powder free latex gloves| latex allergens| primary prevention|ige antibodies| gloves| sensitization| prevalence| workers| nurses	Allmers, H; Schmengler, J; Skudlik, C	Primary prevention of natural rubber latex allergy in the German health care system through education and intervention		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	occupational asthma; natural rubber latex allergy; powder free latex gloves; latex allergens; primary prevention	IGE ANTIBODIES; GLOVES; SENSITIZATION; PREVALENCE; WORKERS; NURSES	Background: The development of occupational asthma and allergic skin reactions caused by natural rubber latex (NRL) allergy are risks for health care workers. There are few published studies to suggest that intervention programs to reduce exposure will lead to primary prevention of sensitization. Objective: This study assesses the effects of intervention to reduce the incidence of NRL allergy in personnel working in health care facilities insured by the German statutory accident insurance company for health care workers, Berufsgenossenschaft fur Gesundheitsdienst und Wohlfahrtspflege, with approximately 3 million insured employees, by switching to powder-free NRL gloves. Methods: The timing of introduction of intervention strategies, such as education of both physicians and administrators, together with regulations demanding that health care facilities only purchase low-protein, powder-free NRL gloves are reported. We reviewed the annual numbers of reported suspected cases of NRL-caused occupational allergies and the amount and type of gloves used in German acute-care hospitals since 1986. Results: The purchase of powder-free NRL examination gloves exceeded that of powdered gloves for the first time in 1998. This only became true for powder-free NRL sterile gloves 2 years later in 2000. The incidence of suspected occupational NRL allergy cases rose until 1998 and has declined steadily since. There was a 2-year lag between the beginning of the decline in the purchase of powdered NRL examination gloves and the beginning of a decline in suspected NRL-caused occupational asthma cases. Conclusions: Despite the effect of increased recognition of NRL allergies, education about NRL allergies in health care facilities combined with the introduction of powder-free gloves with reduced protein levels has been associated with a decline in the number of suspected cases of occupational allergies caused by NRL in Germany on a nationwide scale. These results clearly indicate that primary prevention of occupational NRL allergies can be achieved if these straightforward and practical interventions are properly carried out and maintained.	24	95	2002	6	10.1067/mai.2002.126461	Allergy; Immunology
Placebo-controlled trial of house dust mite-impermeable mattress covers - Effect on symptoms in early childhood. We investigated the effect of house dust mite (HDM)-allergen avoidance on the development of respiratory Symptoms, atopic dermatitis, and atopic sensitization by performing a double blind, placebo-controlled trial. In total, 1,282 allergic pregnant women were selected (416 received HDM allergen-impermeable mattress covers for the parents' and child's mattress in the third trimester of pregnancy [active], 394 received placebo covers, 472 received no intervention). Data on allergen exposure, clinical symptoms, and immunoglobulin E were collected prospectively. The prevalence of night cough without a cold in the second year of life was lower in the group with active covers compared with the group with placebo covers (adjusted odds ratio 0.65; 95% confidence interval 0.4-1.0). No effect of the intervention was seen on other respiratory symptoms, atopic dermatitis, and total and specific immunoglobulin E. It can be concluded that application of HDM-impermeable mattress covers on the child's and parents' beds reduced night cough, but not other respiratory symptoms, atopic dermatitis, and atopic sensitization in the first 2 years of life. Follow-up will determine the long-term effect of the intervention on the development of atopic disease.. mite control| wheezing| asthma| atopy| allergens|der-p-i| respiratory symptoms| allergen exposure| early-life| high-risk| asthma| infants| ige| sensitization| sensitivity.	AUG 1-2002	mite control| wheezing| asthma| atopy| allergens|der-p-i| respiratory symptoms| allergen exposure| early-life| high-risk| asthma| infants| ige| sensitization| sensitivity	Koopman, LP; van Strien, RT; Kerkhof, M; Wijga, A; Smit, HA; de Jongste, JC; Gerritsen, J; Aalberse, RC; Brunekreef, B; Neijens, HJ	Placebo-controlled trial of house dust mite-impermeable mattress covers - Effect on symptoms in early childhood		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	mite control; wheezing; asthma; atopy; allergens	DER-P-I; RESPIRATORY SYMPTOMS; ALLERGEN EXPOSURE; EARLY-LIFE; HIGH-RISK; ASTHMA; INFANTS; IGE; SENSITIZATION; SENSITIVITY	We investigated the effect of house dust mite (HDM)-allergen avoidance on the development of respiratory Symptoms, atopic dermatitis, and atopic sensitization by performing a double blind, placebo-controlled trial. In total, 1,282 allergic pregnant women were selected (416 received HDM allergen-impermeable mattress covers for the parents' and child's mattress in the third trimester of pregnancy [active], 394 received placebo covers, 472 received no intervention). Data on allergen exposure, clinical symptoms, and immunoglobulin E were collected prospectively. The prevalence of night cough without a cold in the second year of life was lower in the group with active covers compared with the group with placebo covers (adjusted odds ratio 0.65; 95% confidence interval 0.4-1.0). No effect of the intervention was seen on other respiratory symptoms, atopic dermatitis, and total and specific immunoglobulin E. It can be concluded that application of HDM-impermeable mattress covers on the child's and parents' beds reduced night cough, but not other respiratory symptoms, atopic dermatitis, and atopic sensitization in the first 2 years of life. Follow-up will determine the long-term effect of the intervention on the development of atopic disease.	28	95	2002	7	10.1164/rccm.2106026	General & Internal Medicine; Respiratory System
Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate. Work in humans and laboratory animals has identified a central role for cytokines and chemokines in development and persistence of lower airway inflammation. The objectives of this study were to determine interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha induction in bronchoalveolar lavage (BAL) of control horses and horses with heaves both during remission and exacerbation of the disease, and to determine the effect of therapy with inhaled fluticasone propionate on the cytokine profile of horses with heaves. IL-1beta and TNF-alpha mRNA expression was significantly higher in horses with heaves after exposure to moldy hay compared to either values obtained during clinical remission or to healthy controls. IL-8 mRNA expression and protein concentrations were significantly higher in horses with heaves than in controls. Both IL-4 and IFN-gamma mRNA expression was increased at various times in heaves-susceptible horses compared to controls. IL-2, IL-5 and IL-10 mRNA expression was not detected in BAL cells of either group. Therapy with inhaled fluticasone propionate after induction of a severe heaves exacerbation resulted in complete resolution of clinical signs, normalization of pulmonary function tests, and significant decrease in BAL neutrophilia. This was associated with a significant decrease in IL-4 mRNA expression and increase in IFN-gamma/IL-4 ratio in horses with heaves. These results demonstrate the clinical efficacy of inhaled fluticasone propionate for the treatment of heaves and suggest a role for cytokines in the development of lower airway inflammation in heaves-susceptible horses. (C) 2002 Elsevier Science B.V. All rights reserved.. cytokine| chemokine| heaves| copd| horse| fluticasone|bronchoalveolar lavage fluid| nf-kappa-b| obstruction heaves| bronchial hyperresponsiveness| phenotypic analysis| straw challenges| peripheral-blood| atopic asthma| animal-model| natural hay.	MAR-2002	cytokine| chemokine| heaves| copd| horse| fluticasone|bronchoalveolar lavage fluid| nf-kappa-b| obstruction heaves| bronchial hyperresponsiveness| phenotypic analysis| straw challenges| peripheral-blood| atopic asthma| animal-model| natural hay	Giguere, S; Viel, L; Lee, E; MacKay, EJ; Hernandez, J; Franchini, M	Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate		VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY	cytokine; chemokine; heaves; COPD; horse; fluticasone	BRONCHOALVEOLAR LAVAGE FLUID; NF-KAPPA-B; OBSTRUCTION HEAVES; BRONCHIAL HYPERRESPONSIVENESS; PHENOTYPIC ANALYSIS; STRAW CHALLENGES; PERIPHERAL-BLOOD; ATOPIC ASTHMA; ANIMAL-MODEL; NATURAL HAY	Work in humans and laboratory animals has identified a central role for cytokines and chemokines in development and persistence of lower airway inflammation. The objectives of this study were to determine interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha induction in bronchoalveolar lavage (BAL) of control horses and horses with heaves both during remission and exacerbation of the disease, and to determine the effect of therapy with inhaled fluticasone propionate on the cytokine profile of horses with heaves. IL-1beta and TNF-alpha mRNA expression was significantly higher in horses with heaves after exposure to moldy hay compared to either values obtained during clinical remission or to healthy controls. IL-8 mRNA expression and protein concentrations were significantly higher in horses with heaves than in controls. Both IL-4 and IFN-gamma mRNA expression was increased at various times in heaves-susceptible horses compared to controls. IL-2, IL-5 and IL-10 mRNA expression was not detected in BAL cells of either group. Therapy with inhaled fluticasone propionate after induction of a severe heaves exacerbation resulted in complete resolution of clinical signs, normalization of pulmonary function tests, and significant decrease in BAL neutrophilia. This was associated with a significant decrease in IL-4 mRNA expression and increase in IFN-gamma/IL-4 ratio in horses with heaves. These results demonstrate the clinical efficacy of inhaled fluticasone propionate for the treatment of heaves and suggest a role for cytokines in the development of lower airway inflammation in heaves-susceptible horses. (C) 2002 Elsevier Science B.V. All rights reserved.	38	95	2002	12	10.1016/S0165-2427(01)00420-2	Immunology; Veterinary Sciences
Does environmental endotoxin exposure prevent asthma?. The evidence as to whether exposure to environmental airborne endotoxin plays a protective or an inducing role in the development of asthma is reviewed. Studies of endotoxin and atopy, endotoxin and asthma, and farming and asthma are considered and, in each instance, a distinction is made between evidence of primary causation and evidence of secondary causation. It is concluded that, although it is plausible that bacterial endotoxin may protect against the development of asthma, there is considerable reason for caution regarding this hypothesis.. animal feed-industry| lung-function changes| in-house dust| inflammatory response| hay-fever| airborne endotoxin| inhaled endotoxin| allergic sensitization| respiratory symptoms| bronchial reactivity.	JAN-2002	animal feed-industry| lung-function changes| in-house dust| inflammatory response| hay-fever| airborne endotoxin| inhaled endotoxin| allergic sensitization| respiratory symptoms| bronchial reactivity	Douwes, J; Pearce, N; Heederik, D	Does environmental endotoxin exposure prevent asthma?		THORAX		ANIMAL FEED-INDUSTRY; LUNG-FUNCTION CHANGES; IN-HOUSE DUST; INFLAMMATORY RESPONSE; HAY-FEVER; AIRBORNE ENDOTOXIN; INHALED ENDOTOXIN; ALLERGIC SENSITIZATION; RESPIRATORY SYMPTOMS; BRONCHIAL REACTIVITY	The evidence as to whether exposure to environmental airborne endotoxin plays a protective or an inducing role in the development of asthma is reviewed. Studies of endotoxin and atopy, endotoxin and asthma, and farming and asthma are considered and, in each instance, a distinction is made between evidence of primary causation and evidence of secondary causation. It is concluded that, although it is plausible that bacterial endotoxin may protect against the development of asthma, there is considerable reason for caution regarding this hypothesis.	89	95	2002	5	10.1136/thorax.57.1.86	Respiratory System
Exposure to cockroach allergen in the home is associated with incident doctor-diagnosed asthma and recurrent wheezing. Background: Indoor inhaled allergens have been repeatedly demonstrated to worsen asthma In sensitized individual, but their role in incident asthma is more controversial, Objective: We investigated the relationship between exposure to allergens (dust mite, cat, and cockroach) measured in the home and incident doctor-diagnosed asthma and recurrent wheezing in children born to parents with asthma, allergies, or both. Methods: From an ongoing longitudinal family and birth cohort study, rye identified 222 siblings (median age, 2.87 years) of the index children. Allergen levels in the home were measured from dust samples obtained at the beginning of the study. Incident doctor-diagnosed asthma and recurrent wheezing were determined from questionnaires administered at 14 months and 22 months after the initial questionnaire, Results: Thirteen (5.9%) children were reported to have Incident asthma, twenty (9.0%) children had recurrent asthmatic wheezing, and 18 (8.1%) had recurrent wheezing without asthma, Compared with children living in homes with Bla g 1 or 2 levels of less than 0.05 U/g, children exposed to Bra g 1 or 2 levels of 0.05 to less than 2 U/g had a relative risk for incident asthma of 8.27 (95% confidence interval, 1.04-66.04), whereas children exposed to Bla g 1 or 2 levels of 2 U/g or greater bad a relative risk for incident asthma of 35.87 (95% confidence Interval, 4.49-286.62). Cockroach allergen exposure was likewise a significant predictor for recurrent asthmatic wheezing. Neither dust mite nor cat allergen levels were significantly associated with either outcome. These findings remained after control for several covariates, Conclusion: Exposure to cockroach allergen early in life may contribute to the development of asthma in susceptible children.. cockroach| indoor allergens| asthma| wheeze|inner-city children| childhood asthma| respiratory illness| united-states| risk factor| sensitization| smoking| race| responsiveness| prevalence.	JAN-2001	cockroach| indoor allergens| asthma| wheeze|inner-city children| childhood asthma| respiratory illness| united-states| risk factor| sensitization| smoking| race| responsiveness| prevalence	Litonjua, AA; Carey, VJ; Burge, HA; Weiss, ST; Gold, DR	Exposure to cockroach allergen in the home is associated with incident doctor-diagnosed asthma and recurrent wheezing		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	cockroach; indoor allergens; asthma; wheeze	INNER-CITY CHILDREN; CHILDHOOD ASTHMA; RESPIRATORY ILLNESS; UNITED-STATES; RISK FACTOR; SENSITIZATION; SMOKING; RACE; RESPONSIVENESS; PREVALENCE	Background: Indoor inhaled allergens have been repeatedly demonstrated to worsen asthma In sensitized individual, but their role in incident asthma is more controversial, Objective: We investigated the relationship between exposure to allergens (dust mite, cat, and cockroach) measured in the home and incident doctor-diagnosed asthma and recurrent wheezing in children born to parents with asthma, allergies, or both. Methods: From an ongoing longitudinal family and birth cohort study, rye identified 222 siblings (median age, 2.87 years) of the index children. Allergen levels in the home were measured from dust samples obtained at the beginning of the study. Incident doctor-diagnosed asthma and recurrent wheezing were determined from questionnaires administered at 14 months and 22 months after the initial questionnaire, Results: Thirteen (5.9%) children were reported to have Incident asthma, twenty (9.0%) children had recurrent asthmatic wheezing, and 18 (8.1%) had recurrent wheezing without asthma, Compared with children living in homes with Bla g 1 or 2 levels of less than 0.05 U/g, children exposed to Bra g 1 or 2 levels of 0.05 to less than 2 U/g had a relative risk for incident asthma of 8.27 (95% confidence interval, 1.04-66.04), whereas children exposed to Bla g 1 or 2 levels of 2 U/g or greater bad a relative risk for incident asthma of 35.87 (95% confidence Interval, 4.49-286.62). Cockroach allergen exposure was likewise a significant predictor for recurrent asthmatic wheezing. Neither dust mite nor cat allergen levels were significantly associated with either outcome. These findings remained after control for several covariates, Conclusion: Exposure to cockroach allergen early in life may contribute to the development of asthma in susceptible children.	29	95	2001	7	10.1067/mai.2001.111143	Allergy; Immunology
Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients. Allergic diseases are characterized by allergic complaints in the shock organ and specific immunoglobulin (Ig)E in serum. Literature data indicate that the nasal mucosa itself could produce at least a large part of the specific IgE in allergic rhinitis patients. In order to investigate this hypothesis, nasal mucosal biopsies from the inferior turbinate were taken from symptomatic grass pollen allergic rhinitis patients, symptomatic house dust mite allergic rhinitis patients and nonallergic healthy controls, confirmed by radioallergosorbent test and skin-prick test, Immunohistochemical double-staining was performed for B-cells (CD19) with IgE, plasma cells (CD138) with IgE and plasma cells with biotinylated allergens. Significantly more IgE-positive B-cells and IgE-positive plasma cells were found in biotinylated a the nasal mucosa of allergic patients than in that of nonallergic controls. Double staining with biotinylated allergens and plasma cells showed allergen-positive plasma cells in the nasal mucosa of allergic patients and no allergen-positive plasma cells in the nasal mucosa of nonallergic patients. Blocking experiments using polyclonal antibodies directed against IgE showed a significant reduction in the number of allergen-positive cells in contrast to experiments using polyclonal antibodies directed against IgG, IgA or IgM. This study describes new evidence that specific immunoglobulin E is produced locally in the nasal mucosa in patients with seasonal allergic rhinitis and perennial allergic rhinitis, but not in nonallergic controls.. allergic rhinitis| b-cells| biotinylated allergen| nasal mucosa| plasma cells| specific ige|messenger-rna| mast-cells| mucosa| expression| il-4| antibodies| challenge| induction| polyps| lung.	MAR-2000	allergic rhinitis| b-cells| biotinylated allergen| nasal mucosa| plasma cells| specific ige|messenger-rna| mast-cells| mucosa| expression| il-4| antibodies| challenge| induction| polyps| lung	KleinJan, A; Vinke, JG; Severijnen, LWFM; Fokkens, WJ	Local production and detection of (specific) IgE in nasal B-cells and plasma cells of allergic rhinitis patients		EUROPEAN RESPIRATORY JOURNAL	allergic rhinitis; B-cells; biotinylated allergen; nasal mucosa; plasma cells; specific IgE	MESSENGER-RNA; MAST-CELLS; MUCOSA; EXPRESSION; IL-4; ANTIBODIES; CHALLENGE; INDUCTION; POLYPS; LUNG	Allergic diseases are characterized by allergic complaints in the shock organ and specific immunoglobulin (Ig)E in serum. Literature data indicate that the nasal mucosa itself could produce at least a large part of the specific IgE in allergic rhinitis patients. In order to investigate this hypothesis, nasal mucosal biopsies from the inferior turbinate were taken from symptomatic grass pollen allergic rhinitis patients, symptomatic house dust mite allergic rhinitis patients and nonallergic healthy controls, confirmed by radioallergosorbent test and skin-prick test, Immunohistochemical double-staining was performed for B-cells (CD19) with IgE, plasma cells (CD138) with IgE and plasma cells with biotinylated allergens. Significantly more IgE-positive B-cells and IgE-positive plasma cells were found in biotinylated a the nasal mucosa of allergic patients than in that of nonallergic controls. Double staining with biotinylated allergens and plasma cells showed allergen-positive plasma cells in the nasal mucosa of allergic patients and no allergen-positive plasma cells in the nasal mucosa of nonallergic patients. Blocking experiments using polyclonal antibodies directed against IgE showed a significant reduction in the number of allergen-positive cells in contrast to experiments using polyclonal antibodies directed against IgG, IgA or IgM. This study describes new evidence that specific immunoglobulin E is produced locally in the nasal mucosa in patients with seasonal allergic rhinitis and perennial allergic rhinitis, but not in nonallergic controls.	34	95	2000	7	10.1034/j.1399-3003.2000.15.11.x	Respiratory System
New concept of the pathogenesis of atopic dermatitis: Interplay among the barrier, allergy, and pruritus as a trinity. Atopic dermatitis (AD) is a common skin condition, characterized by a complex, heterogeneous pathogenesis, including skin barrier dysfunctions, allergy/immunology, and pruritus. When the skin barrier is disrupted by, for example, the filaggrin gene mutation and/or environmental factors, the skin is predisposed to being penetrated by external stimuli. Foreign antigens can be subdivided into two subsets by size: haptens (including metals) and protein antigens. It is known that a single hapten challenge provokes Th1 initially, but that repeated elicitation with haptens results in a shift toward Th2-dominated responses. On the other hand, exposure to protein antigens directly induces Th2-dominant conditions via the thymic stromal lymphopoietin (TSLP) receptor on Langerhans cells. Recently, it has been revealed that Th2 cells produce IL-31, which provokes pruritus, and that Th2 cytokines decrease filaggrin expressions by keratinocytes. These findings suggest that Th2 conditions lead to pruritus and barrier dysfunctions. In this review, we will examine the highly complex interplay among skin barrier abnormality, allergy/immunology, and pruritus as a trinity in the development of AD. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.. atopic dermatitis| skin barrier| filaggrin| langerhans cells| pruritus| hapten-atopy hypothesis|regulatory t-cells| langerin(+) dendritic cells| stromal lymphopoietin expression| of-function variants| langerhans cells| immune-responses| nc/nga mice| contact-dermatitis| skin inflammation| th17 cells.	APR-2013	atopic dermatitis| skin barrier| filaggrin| langerhans cells| pruritus| hapten-atopy hypothesis|regulatory t-cells| langerin(+) dendritic cells| stromal lymphopoietin expression| of-function variants| langerhans cells| immune-responses| nc/nga mice| contact-dermatitis| skin inflammation| th17 cells	Kabashima, K	New concept of the pathogenesis of atopic dermatitis: Interplay among the barrier, allergy, and pruritus as a trinity		JOURNAL OF DERMATOLOGICAL SCIENCE	Atopic dermatitis; Skin barrier; Filaggrin; Langerhans cells; Pruritus; Hapten-atopy hypothesis	REGULATORY T-CELLS; LANGERIN(+) DENDRITIC CELLS; STROMAL LYMPHOPOIETIN EXPRESSION; OF-FUNCTION VARIANTS; LANGERHANS CELLS; IMMUNE-RESPONSES; NC/NGA MICE; CONTACT-DERMATITIS; SKIN INFLAMMATION; TH17 CELLS	Atopic dermatitis (AD) is a common skin condition, characterized by a complex, heterogeneous pathogenesis, including skin barrier dysfunctions, allergy/immunology, and pruritus. When the skin barrier is disrupted by, for example, the filaggrin gene mutation and/or environmental factors, the skin is predisposed to being penetrated by external stimuli. Foreign antigens can be subdivided into two subsets by size: haptens (including metals) and protein antigens. It is known that a single hapten challenge provokes Th1 initially, but that repeated elicitation with haptens results in a shift toward Th2-dominated responses. On the other hand, exposure to protein antigens directly induces Th2-dominant conditions via the thymic stromal lymphopoietin (TSLP) receptor on Langerhans cells. Recently, it has been revealed that Th2 cells produce IL-31, which provokes pruritus, and that Th2 cytokines decrease filaggrin expressions by keratinocytes. These findings suggest that Th2 conditions lead to pruritus and barrier dysfunctions. In this review, we will examine the highly complex interplay among skin barrier abnormality, allergy/immunology, and pruritus as a trinity in the development of AD. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.	102	94	2013	9	10.1016/j.jdermsci.2013.02.001	Dermatology
Altered stratum corneum barrier and enhanced percutaneous immune responses in filaggrin-null mice. Background: Loss-of-function mutations in filaggrin are major predisposing factors for atopic dermatitis. Although various reports suggest a critical role for filaggrin in stratum corneum (SC) barrier formation, the lack of filaggrin-null (Flg(-/-)) mice has hampered detailed in vivo analysis of filaggrin's functions. Objective: We sought to generate Flg(-/-) mice and to assess the effect of filaggrin loss on SC barrier function and percutaneous immune responses. Methods: We generated Flg(-/-) mice using gene targeting and assessed the morphology, hydration, mechanical strength, and antigen permeability of their SC. Percutaneous immune responses were evaluated through irritant-and hapten-induced contact hypersensitivity studies and by measuring humoral responses to epicutaneous sensitization with protein antigen. Results: Newborn Flg(-/-) mice exhibited dry scaly skin. Despite marked decreases in natural moisturizing factor levels, which are filaggrin degradation products, SC hydration and transepidermal water loss were normal. Microscopic analyses suggested premature shedding of SC layers, and indeed, increased desquamation under mechanical stress was demonstrated. Loss of keratin patterns, which are critical for corneocyte stabilization, is likely attributable to fragility in the Flg(-/-) SC. Antigens penetrated the Flg(-/-) SC more efficiently, leading to enhanced responses in hapten-induced contact hypersensitivity and higher serum levels of anti-ovalbumin IgG(1) and IgE. Conclusion: Complete filaggrin deficiency led to altered barrier integrity and enhanced sensitization, which are important factors in early-phase atopic dermatitis. Flg(-/-) mice should provide a valuable tool to further explore additional factors the dysfunction of which leads to uncontrolled inflammation in patients with atopic diseases. (J Allergy Clin Immunol 2012;129:1538-46.). filaggrin| filaggrin-null mice| atopic dermatitis| ichthyosis vulgaris| barrier function| flaky tail mice| stratum corneum| percutaneous immune response|of-function mutations| ichthyosis-vulgaris| atopic-dermatitis| skin-barrier| house-mouse| flaky tail| clinical severity| keratin filaments| langerhans cells| disease.	JUN-2012	filaggrin| filaggrin-null mice| atopic dermatitis| ichthyosis vulgaris| barrier function| flaky tail mice| stratum corneum| percutaneous immune response|of-function mutations| ichthyosis-vulgaris| atopic-dermatitis| skin-barrier| house-mouse| flaky tail| clinical severity| keratin filaments| langerhans cells| disease	Kawasaki, H; Nagao, K; Kubo, A; Hata, T; Shimizu, A; Mizuno, H; Yamada, T; Amagai, M	Altered stratum corneum barrier and enhanced percutaneous immune responses in filaggrin-null mice		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Filaggrin; filaggrin-null mice; atopic dermatitis; ichthyosis vulgaris; barrier function; flaky tail mice; stratum corneum; percutaneous immune response	OF-FUNCTION MUTATIONS; ICHTHYOSIS-VULGARIS; ATOPIC-DERMATITIS; SKIN-BARRIER; HOUSE-MOUSE; FLAKY TAIL; CLINICAL SEVERITY; KERATIN FILAMENTS; LANGERHANS CELLS; DISEASE	Background: Loss-of-function mutations in filaggrin are major predisposing factors for atopic dermatitis. Although various reports suggest a critical role for filaggrin in stratum corneum (SC) barrier formation, the lack of filaggrin-null (Flg(-/-)) mice has hampered detailed in vivo analysis of filaggrin's functions. Objective: We sought to generate Flg(-/-) mice and to assess the effect of filaggrin loss on SC barrier function and percutaneous immune responses. Methods: We generated Flg(-/-) mice using gene targeting and assessed the morphology, hydration, mechanical strength, and antigen permeability of their SC. Percutaneous immune responses were evaluated through irritant-and hapten-induced contact hypersensitivity studies and by measuring humoral responses to epicutaneous sensitization with protein antigen. Results: Newborn Flg(-/-) mice exhibited dry scaly skin. Despite marked decreases in natural moisturizing factor levels, which are filaggrin degradation products, SC hydration and transepidermal water loss were normal. Microscopic analyses suggested premature shedding of SC layers, and indeed, increased desquamation under mechanical stress was demonstrated. Loss of keratin patterns, which are critical for corneocyte stabilization, is likely attributable to fragility in the Flg(-/-) SC. Antigens penetrated the Flg(-/-) SC more efficiently, leading to enhanced responses in hapten-induced contact hypersensitivity and higher serum levels of anti-ovalbumin IgG(1) and IgE. Conclusion: Complete filaggrin deficiency led to altered barrier integrity and enhanced sensitization, which are important factors in early-phase atopic dermatitis. Flg(-/-) mice should provide a valuable tool to further explore additional factors the dysfunction of which leads to uncontrolled inflammation in patients with atopic diseases. (J Allergy Clin Immunol 2012;129:1538-46.)	48	94	2012	15	10.1016/j.jaci.2012.01.068	Allergy; Immunology
Mast Cells Increase Vascular Permeability by Heparin-Initiated Bradykinin Formation In Vivo. Activated mast cells trigger edema in allergic and inflammatory disease. We report a paracrine mechanism by which mast cell-released heparin increases vascular permeability in vivo. Heparin activated the protease factor XII, which initiates bradykinin formation in plasma. Targeting factor XII or kinin B2 receptors abolished heparin-triggered leukocyte-endothelium adhesion and interfered with a mast cell-driven drop in blood pressure in rodents. Intravital laser scanning microscopy and tracer measurements showed heparin-driven fluid extravasation in mouse skin microvessels. Ablation of factor XII or kinin B2 receptors abolished heparin-induced skin edema and protected mice from allergen-activated mast cell-driven leakage. In contrast, heparin and activated mast cells induced excessive edema in mice deficient in the major inhibitor of factor XII, Cl esterase inhibitor. Allergen exposure triggered edema attacks in hereditary angioedema patients, lacking Cl esterase inhibitor. The data indicate that heparin-initiated bradykinin formation plays a fundamental role in mast cell-mediated diseases.. coagulation-factor-xii| adverse clinical events| chondroitin sulfate-e| hereditary angioedema| contact system| allergic reactions| activation| mechanisms| receptor| enzyme.	FEB 25-2011	coagulation-factor-xii| adverse clinical events| chondroitin sulfate-e| hereditary angioedema| contact system| allergic reactions| activation| mechanisms| receptor| enzyme	Oschatz, C; Maas, C; Lecher, B; Jansen, T; Bjorkqvist, J; Tradler, T; Sedlmeier, R; Burfeind, P; Cichon, S; Hammerschmidt, S; Muller-Esterl, W; Wuillemin, WA; Nilsson, G; Renne, T	Mast Cells Increase Vascular Permeability by Heparin-Initiated Bradykinin Formation In Vivo		IMMUNITY		COAGULATION-FACTOR-XII; ADVERSE CLINICAL EVENTS; CHONDROITIN SULFATE-E; HEREDITARY ANGIOEDEMA; CONTACT SYSTEM; ALLERGIC REACTIONS; ACTIVATION; MECHANISMS; RECEPTOR; ENZYME	Activated mast cells trigger edema in allergic and inflammatory disease. We report a paracrine mechanism by which mast cell-released heparin increases vascular permeability in vivo. Heparin activated the protease factor XII, which initiates bradykinin formation in plasma. Targeting factor XII or kinin B2 receptors abolished heparin-triggered leukocyte-endothelium adhesion and interfered with a mast cell-driven drop in blood pressure in rodents. Intravital laser scanning microscopy and tracer measurements showed heparin-driven fluid extravasation in mouse skin microvessels. Ablation of factor XII or kinin B2 receptors abolished heparin-induced skin edema and protected mice from allergen-activated mast cell-driven leakage. In contrast, heparin and activated mast cells induced excessive edema in mice deficient in the major inhibitor of factor XII, Cl esterase inhibitor. Allergen exposure triggered edema attacks in hereditary angioedema patients, lacking Cl esterase inhibitor. The data indicate that heparin-initiated bradykinin formation plays a fundamental role in mast cell-mediated diseases.	53	94	2011	11	10.1016/j.immuni.2011.02.008	Immunology
Prenatal Maternal Stress and Cord Blood Innate and Adaptive Cytokine Responses in an Inner-City Cohort. Rationale: Stress-elicited disruption of immunity begins in utero. Objectives: Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families). Methods: Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age). Measurements and Main Results Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-a to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced Conclusions Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.. psychological stress| cord blood| cytokines| innate| adaptive|respiratory syncytial virus| t-regulatory cells| immune-responses| airway inflammation| dendritic cells| asthma| maturation| pregnancy| allergens| children.	JUL 1-2010	psychological stress| cord blood| cytokines| innate| adaptive|respiratory syncytial virus| t-regulatory cells| immune-responses| airway inflammation| dendritic cells| asthma| maturation| pregnancy| allergens| children	Wright, RJ; Visness, CM; Calatroni, A; Grayson, MH; Gold, DR; Sandel, MT; Lee-Parritz, A; Wood, RA; Kattan, M; Bloomberg, GR; Burger, M; Togias, A; Witter, FR; Sperling, RS; Sadovsky, Y; Gern, JE	Prenatal Maternal Stress and Cord Blood Innate and Adaptive Cytokine Responses in an Inner-City Cohort		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	psychological stress; cord blood; cytokines; innate; adaptive	RESPIRATORY SYNCYTIAL VIRUS; T-REGULATORY CELLS; IMMUNE-RESPONSES; AIRWAY INFLAMMATION; DENDRITIC CELLS; ASTHMA; MATURATION; PREGNANCY; ALLERGENS; CHILDREN	Rationale: Stress-elicited disruption of immunity begins in utero. Objectives: Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families). Methods: Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age). Measurements and Main Results Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-a to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced Conclusions Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.	59	94	2010	9	10.1164/rccm.200904-0637OC	General & Internal Medicine; Respiratory System
Nrf2 protects against airway disorders. Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, air-way, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome Or lung cancer, which further supports the role for NRF2 in these lung diseases. In the Current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies. Published by Elsevier Inc.. are| keap1| lung| knockout mice| oxidant| polymorphism| mutation|respiratory syncytial virus| antioxidant response element| transcription factor nrf2| induced lung injury| glutathione-s-transferase| extracellular-superoxide dismutase| idiopathic pulmonary-fibrosis| transpeptidase-deficient mice| induced inflammatory response| adenovirus-mediated transfer.	APR 1-2010	are| keap1| lung| knockout mice| oxidant| polymorphism| mutation|respiratory syncytial virus| antioxidant response element| transcription factor nrf2| induced lung injury| glutathione-s-transferase| extracellular-superoxide dismutase| idiopathic pulmonary-fibrosis| transpeptidase-deficient mice| induced inflammatory response| adenovirus-mediated transfer	Cho, HY; Kleeberger, SR	Nrf2 protects against airway disorders		TOXICOLOGY AND APPLIED PHARMACOLOGY	ARE; Keap1; Lung; Knockout mice; Oxidant; Polymorphism; Mutation	RESPIRATORY SYNCYTIAL VIRUS; ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR NRF2; INDUCED LUNG INJURY; GLUTATHIONE-S-TRANSFERASE; EXTRACELLULAR-SUPEROXIDE DISMUTASE; IDIOPATHIC PULMONARY-FIBROSIS; TRANSPEPTIDASE-DEFICIENT MICE; INDUCED INFLAMMATORY RESPONSE; ADENOVIRUS-MEDIATED TRANSFER	Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, air-way, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome Or lung cancer, which further supports the role for NRF2 in these lung diseases. In the Current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies. Published by Elsevier Inc.	183	94	2010	14	10.1016/j.taap.2009.07.024	Pharmacology & Pharmacy; Toxicology
Asthma and pregnancy: emerging evidence of epigenetic interactions in utero. Purpose of review Pregnancy is arguably the most critical period of developmental programming. Here, we particularly focus on the emerging paradigm that disease propensity is epigenetically determined by maternal exposures that have the capacity to activate or silence fetal genes through alterations in DNA and histone methylation, histone acetylation, and chromatin structure. Recent findings The most notable recent candidate to emerge in this role has been dietary folate, a methyl donor clearly associated with changes in gene expression and disease susceptibility through gene hypermethylation. Animal studies also provide the first evidence that the allergy protective effects of microbial exposure in pregnancy may be mediated by changes in methylation of Th1 genes of the offspring. There is also emerging evidence that perinatal differences in immune function of allergy-prone newborns extend beyond previously recognized differences in effector T cell (Th1/Th2) function, to also include differences in neonatal regulatory T cell (Treg) and Th17 function, and moreover, that these pathways are also epigenetically regulated. Summary New studies reinforce the importance of in-utero exposures (including dietary nutrients, microbial products, cigarette smoking, and certain maternal mediations) in fetal immune development and in programming the susceptibility to asthma and allergic disease.. allergic disease| asthma| cord blood| cytokines| epigenetics| fetus| folate| maternal diet| pregnancy|regulatory t-cells| population-based register| tobacco-smoke exposure| maternal asthma| cord blood| childhood asthma| cesarean-section| fetal sex| allergic sensitization| gene-expression.	OCT-2009	allergic disease| asthma| cord blood| cytokines| epigenetics| fetus| folate| maternal diet| pregnancy|regulatory t-cells| population-based register| tobacco-smoke exposure| maternal asthma| cord blood| childhood asthma| cesarean-section| fetal sex| allergic sensitization| gene-expression	Prescott, SL; Clifton, V	Asthma and pregnancy: emerging evidence of epigenetic interactions in utero		CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY	allergic disease; asthma; cord blood; cytokines; epigenetics; fetus; folate; maternal diet; pregnancy	REGULATORY T-CELLS; POPULATION-BASED REGISTER; TOBACCO-SMOKE EXPOSURE; MATERNAL ASTHMA; CORD BLOOD; CHILDHOOD ASTHMA; CESAREAN-SECTION; FETAL SEX; ALLERGIC SENSITIZATION; GENE-EXPRESSION	Purpose of review Pregnancy is arguably the most critical period of developmental programming. Here, we particularly focus on the emerging paradigm that disease propensity is epigenetically determined by maternal exposures that have the capacity to activate or silence fetal genes through alterations in DNA and histone methylation, histone acetylation, and chromatin structure. Recent findings The most notable recent candidate to emerge in this role has been dietary folate, a methyl donor clearly associated with changes in gene expression and disease susceptibility through gene hypermethylation. Animal studies also provide the first evidence that the allergy protective effects of microbial exposure in pregnancy may be mediated by changes in methylation of Th1 genes of the offspring. There is also emerging evidence that perinatal differences in immune function of allergy-prone newborns extend beyond previously recognized differences in effector T cell (Th1/Th2) function, to also include differences in neonatal regulatory T cell (Treg) and Th17 function, and moreover, that these pathways are also epigenetically regulated. Summary New studies reinforce the importance of in-utero exposures (including dietary nutrients, microbial products, cigarette smoking, and certain maternal mediations) in fetal immune development and in programming the susceptibility to asthma and allergic disease.	97	94	2009	10	10.1097/ACI.0b013e328330634f	Allergy; Immunology
Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway. Background: Cellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals. Objective: We conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects. Methods: Study subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing. Results: All subjects tolerated oral sulforaphane dosing without significant adverse events. Increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner with maximal enzyme induction observed at the highest dose of 200 g broccoli sprouts prepared as BSH. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. Phase II enzyme induction was not seen with ingestion of non-sulforaphane containing alfalfa sprouts.. oxidative stress| antioxidants| asthma| allergic inflammation| sulforaphane| phase ii enzymes| air pollution|diesel exhaust particles| oxidative stress| broccoli sprouts| quantitative-determination| cruciferous vegetables| nasal challenge| ige production| in-vivo| isothiocyanates| asthma.	MAR-2009	oxidative stress| antioxidants| asthma| allergic inflammation| sulforaphane| phase ii enzymes| air pollution|diesel exhaust particles| oxidative stress| broccoli sprouts| quantitative-determination| cruciferous vegetables| nasal challenge| ige production| in-vivo| isothiocyanates| asthma	Riedl, MA; Saxon, A; Diaz-Sanchez, D	Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway		CLINICAL IMMUNOLOGY	Oxidative stress; Antioxidants; Asthma; Allergic inflammation; Sulforaphane; Phase II enzymes; Air pollution	DIESEL EXHAUST PARTICLES; OXIDATIVE STRESS; BROCCOLI SPROUTS; QUANTITATIVE-DETERMINATION; CRUCIFEROUS VEGETABLES; NASAL CHALLENGE; IGE PRODUCTION; IN-VIVO; ISOTHIOCYANATES; ASTHMA	Background: Cellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals. Objective: We conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects. Methods: Study subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing. Results: All subjects tolerated oral sulforaphane dosing without significant adverse events. Increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner with maximal enzyme induction observed at the highest dose of 200 g broccoli sprouts prepared as BSH. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. Phase II enzyme induction was not seen with ingestion of non-sulforaphane containing alfalfa sprouts.	48	94	2009	8	10.1016/j.clim.2008.10.007	Immunology
Maternal smoking habits and cognitive development of children at age 4 years in a population-based birth cohort. Background Active maternal smoking during pregnancy has been associated with a higher risk of behavioural disorders in children, but a few cohort studies measuring smoking data prospectively have studied its specific effects on the cognitive abilities of pre-schoolers. Method A birth cohort was set up in Menorca Island in 1997 within the Asthma Multicenter Infants Cohort Study. A total of 420 (87% of those eligible) children had complete data for final analyses at age 4 years. Interviewer-administered questionnaires were completed by mothers during the third trimester of pregnancy and then every year up to age 4 years of their child. A standardized version of the McCarthy Scales of Children's Abilities (MCSA) was used to evaluate the child's motor and cognitive capabilities. Multivariable regressions were used with MCSA`s assessed outcomes adjusting for: home location, maternal alcohol consumption, mother's social class and level of education during pregnancy, parity, marital status, father's education level, child's gender, birth weight and height, breastfeeding duration, passive smoking, school season, age during test administration and evaluator (psychologist). Results A high global consistency in maternal smoking habits was found (total agreement= 88.7%). Maternal social class and education level were inversely associated with maternal smoking behaviour. Maternal smoking during pregnancy (in cig./day) was associated with a decrease (in points) of children's global cognitive score [beta=-0.60, (95% CI: -1.10; -0.09)]; as wen as global cognitive sub-areas like verbal score [beta = -0.59, (95% CI: -1.11; -0.07)]; quantitative score [beta=-0.57, (95% CI: -1.08; -0.06)]; executive function score [beta = -0.71, (95% CI: -1.23; -0.20)]; and working memory score [beta=-0.46, (95% CI: -0.92; -0.01)]. Conclusion Our findings suggest an association with maternal smoking during pregnancy and lowered cognitive development in children at age 4 years.. maternal smoking habits| smoking during pregnancy| paternal smoking habits| cognitive development| neurocognitive functions| pre-school children| populatin based study| birth cohort|follow-up| pregnant-women| in-utero| exposure| alcohol| tobacco| cigarettes| marijuana| risk| neurodevelopment.	AUG-2007	maternal smoking habits| smoking during pregnancy| paternal smoking habits| cognitive development| neurocognitive functions| pre-school children| populatin based study| birth cohort|follow-up| pregnant-women| in-utero| exposure| alcohol| tobacco| cigarettes| marijuana| risk| neurodevelopment	Julvez, J; Ribas-Fito, N; Torrent, M; Forns, M; Garcia-Esteban, R; Sunyer, J	Maternal smoking habits and cognitive development of children at age 4 years in a population-based birth cohort		INTERNATIONAL JOURNAL OF EPIDEMIOLOGY	maternal smoking habits; smoking during pregnancy; paternal smoking habits; cognitive development; neurocognitive functions; pre-school children; populatin based study; birth cohort	FOLLOW-UP; PREGNANT-WOMEN; IN-UTERO; EXPOSURE; ALCOHOL; TOBACCO; CIGARETTES; MARIJUANA; RISK; NEURODEVELOPMENT	Background Active maternal smoking during pregnancy has been associated with a higher risk of behavioural disorders in children, but a few cohort studies measuring smoking data prospectively have studied its specific effects on the cognitive abilities of pre-schoolers. Method A birth cohort was set up in Menorca Island in 1997 within the Asthma Multicenter Infants Cohort Study. A total of 420 (87% of those eligible) children had complete data for final analyses at age 4 years. Interviewer-administered questionnaires were completed by mothers during the third trimester of pregnancy and then every year up to age 4 years of their child. A standardized version of the McCarthy Scales of Children's Abilities (MCSA) was used to evaluate the child's motor and cognitive capabilities. Multivariable regressions were used with MCSA`s assessed outcomes adjusting for: home location, maternal alcohol consumption, mother's social class and level of education during pregnancy, parity, marital status, father's education level, child's gender, birth weight and height, breastfeeding duration, passive smoking, school season, age during test administration and evaluator (psychologist). Results A high global consistency in maternal smoking habits was found (total agreement= 88.7%). Maternal social class and education level were inversely associated with maternal smoking behaviour. Maternal smoking during pregnancy (in cig./day) was associated with a decrease (in points) of children's global cognitive score [beta=-0.60, (95% CI: -1.10; -0.09)]; as wen as global cognitive sub-areas like verbal score [beta = -0.59, (95% CI: -1.11; -0.07)]; quantitative score [beta=-0.57, (95% CI: -1.08; -0.06)]; executive function score [beta = -0.71, (95% CI: -1.23; -0.20)]; and working memory score [beta=-0.46, (95% CI: -0.92; -0.01)]. Conclusion Our findings suggest an association with maternal smoking during pregnancy and lowered cognitive development in children at age 4 years.	44	94	2007	8	10.1093/ije/dym107	Public, Environmental & Occupational Health
Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring. Clinical studies indicate that maternal exposure to probiotic bacteria may protect from the development of allergic disease later in life. The purpose of this study was to analyse the effects of a perinatal Lactobacillus rhamnosus GG (LGG) supplementation on the development of allergic disorders in offspring. Female BALB/c mice received intragastric LGG every other day before conception, during pregnancy and lactation (perinatal supplementation group) or before conception and during pregnancy only (prenatal supplementation group). Cytokine expression of placental tissues was examined. Offspring of LGG-supplemented and sham-exposed mothers were sensitized to Ovalbumin (OVA), followed by aerosol allergen challenges. Development of experimental asthma was assessed by bronchoalveolar lavage analysis, lung histology and lung function measurement. Cytokine production of splenic mononuclear cells was analysed following in vitro stimulation. Intestinal colonization with LGG was observed in mother mice only, but not in the offspring. However, a reduced expression of TNF-alpha, IFN-gamma, IL-5 as well as IL-10 was observed in mice derived from perinatally LGG-supplemented mothers, whereas IL-13 and IL-4 expression remained unchanged. Moreover, in offspring of prenatally or perinatally LGG-supplemented mothers allergic airway and peribronchial inflammation as well as goblet cell hyperplasia were significantly reduced as compared with mice derived from non-supplemented mothers. In contrast, airway hyperresponsiveness to methacholine was not affected. Exposure to LGG during pregnancy only shifted the placental cytokine expression pattern with a markedly increased TNF-alpha level. Our data suggest that LGG may exert beneficial effects on the development of experimental allergic asthma, when applied in a very early phase of life. Immunological effects are, at least in parts, mediated via the placenta, probably by induction of pro-inflammatory cell signals.. airway inflammation| allergy| materno-fetal interaction| mice| probiotics|placebo-controlled trial| dendritic cell-function| cd4(+) t-cells| murine model| probiotic bacteria| atopic disease| experimental asthma| hygiene hypothesis| immune-system| food allergy.	MAR-2007	airway inflammation| allergy| materno-fetal interaction| mice| probiotics|placebo-controlled trial| dendritic cell-function| cd4(+) t-cells| murine model| probiotic bacteria| atopic disease| experimental asthma| hygiene hypothesis| immune-system| food allergy	Blumer, N; Sel, S; Virna, S; Patrascan, CC; Zimmermann, S; Herz, U; Renz, H; Garn, H	Perinatal maternal application of Lactobacillus rhamnosus GG suppresses allergic airway inflammation in mouse offspring		CLINICAL AND EXPERIMENTAL ALLERGY	airway inflammation; allergy; materno-fetal interaction; mice; probiotics	PLACEBO-CONTROLLED TRIAL; DENDRITIC CELL-FUNCTION; CD4(+) T-CELLS; MURINE MODEL; PROBIOTIC BACTERIA; ATOPIC DISEASE; EXPERIMENTAL ASTHMA; HYGIENE HYPOTHESIS; IMMUNE-SYSTEM; FOOD ALLERGY	Clinical studies indicate that maternal exposure to probiotic bacteria may protect from the development of allergic disease later in life. The purpose of this study was to analyse the effects of a perinatal Lactobacillus rhamnosus GG (LGG) supplementation on the development of allergic disorders in offspring. Female BALB/c mice received intragastric LGG every other day before conception, during pregnancy and lactation (perinatal supplementation group) or before conception and during pregnancy only (prenatal supplementation group). Cytokine expression of placental tissues was examined. Offspring of LGG-supplemented and sham-exposed mothers were sensitized to Ovalbumin (OVA), followed by aerosol allergen challenges. Development of experimental asthma was assessed by bronchoalveolar lavage analysis, lung histology and lung function measurement. Cytokine production of splenic mononuclear cells was analysed following in vitro stimulation. Intestinal colonization with LGG was observed in mother mice only, but not in the offspring. However, a reduced expression of TNF-alpha, IFN-gamma, IL-5 as well as IL-10 was observed in mice derived from perinatally LGG-supplemented mothers, whereas IL-13 and IL-4 expression remained unchanged. Moreover, in offspring of prenatally or perinatally LGG-supplemented mothers allergic airway and peribronchial inflammation as well as goblet cell hyperplasia were significantly reduced as compared with mice derived from non-supplemented mothers. In contrast, airway hyperresponsiveness to methacholine was not affected. Exposure to LGG during pregnancy only shifted the placental cytokine expression pattern with a markedly increased TNF-alpha level. Our data suggest that LGG may exert beneficial effects on the development of experimental allergic asthma, when applied in a very early phase of life. Immunological effects are, at least in parts, mediated via the placenta, probably by induction of pro-inflammatory cell signals.	43	94	2007	10	10.1111/j.1365-2222.2007.02671.x	Allergy; Immunology
Chlorinated pool attendance, atopy, and the risk of asthma during childhood. The pool chlorine hypothesis postulates that the rise in childhood asthma in the developed world could result at least partly from the increasing exposure of children to toxic gases and aerosols contaminating the air of indoor chlorinated pools. To further assess this hypothesis, we explored the relationships between childhood asthma, atopy, and cumulated pool attendance (CPA). We studied 341 schoolchildren 10-13 years of age who attended at a variable rate the same public pool in Brussels (trichloramine in air, 0.3-0.5 mg/m(3)). Examination of the children included a questionnaire, an exercise-induced bronchoconstriction (EIB) test, and the measurement of exhaled nitric oxide (eNO) and total and aeroallergen-specific serum IgE. CPA by children (range, 0-1,818 hr) emerged among the most consistent predictors of asthma (doctor diagnosed or screened with the EIB test) and of elevated eNO, ranking immediately after atopy and family history of asthma or hay fever. Although the risk of elevated eNO increased with CPA [odds ratio (OR) = 1.30; 95% confidence interval (CI), 1.10-1.43] independently of total or specific serum IgE, the probability of developing asthma increased with CPA only in children with serum IgE > 100 kIU/L (OR for each 100-hr increase in CPA = 1.79; 95% CI, 1.07-2.72). All these effects were dose related and most strongly linked to pool attendance before 6-7 years of age. Use of indoor chlorinated pools especially by young children interacts with atopic status to promote the development of childhood asthma. These findings further support the hypothesis implicating pool chlorine in the rise of childhood asthma in industrialized countries. Key words: aeroallergens, atopy, childhood asthma, chlorine, exercise-induced asthma, exhaled nitric oxide, nitrogen trichloride, swimming pool, total IgE, trichloramine.. aeroallergens| atopy| childhood asthma| chlorine| exercise-induced asthma| exhaled nitric oxide| nitrogen trichloride| swimming pool| total ige| trichloramine|serum immunoglobulin-e| nitrogen trichloride| hygiene hypothesis| swimming pools| sodium-hypochlorite| tight junctions| nitric-oxide| lung| schoolchildren| chloramines.	OCT-2006	aeroallergens| atopy| childhood asthma| chlorine| exercise-induced asthma| exhaled nitric oxide| nitrogen trichloride| swimming pool| total ige| trichloramine|serum immunoglobulin-e| nitrogen trichloride| hygiene hypothesis| swimming pools| sodium-hypochlorite| tight junctions| nitric-oxide| lung| schoolchildren| chloramines	Bernard, A; Carbonnelle, S; de Burbure, C; Michel, O; Nickmilder, M	Chlorinated pool attendance, atopy, and the risk of asthma during childhood		ENVIRONMENTAL HEALTH PERSPECTIVES	aeroallergens; atopy; childhood asthma; chlorine; exercise-induced asthma; exhaled nitric oxide; nitrogen trichloride; swimming pool; total IgE; trichloramine	SERUM IMMUNOGLOBULIN-E; NITROGEN TRICHLORIDE; HYGIENE HYPOTHESIS; SWIMMING POOLS; SODIUM-HYPOCHLORITE; TIGHT JUNCTIONS; NITRIC-OXIDE; LUNG; SCHOOLCHILDREN; CHLORAMINES	The pool chlorine hypothesis postulates that the rise in childhood asthma in the developed world could result at least partly from the increasing exposure of children to toxic gases and aerosols contaminating the air of indoor chlorinated pools. To further assess this hypothesis, we explored the relationships between childhood asthma, atopy, and cumulated pool attendance (CPA). We studied 341 schoolchildren 10-13 years of age who attended at a variable rate the same public pool in Brussels (trichloramine in air, 0.3-0.5 mg/m(3)). Examination of the children included a questionnaire, an exercise-induced bronchoconstriction (EIB) test, and the measurement of exhaled nitric oxide (eNO) and total and aeroallergen-specific serum IgE. CPA by children (range, 0-1,818 hr) emerged among the most consistent predictors of asthma (doctor diagnosed or screened with the EIB test) and of elevated eNO, ranking immediately after atopy and family history of asthma or hay fever. Although the risk of elevated eNO increased with CPA [odds ratio (OR) = 1.30; 95% confidence interval (CI), 1.10-1.43] independently of total or specific serum IgE, the probability of developing asthma increased with CPA only in children with serum IgE > 100 kIU/L (OR for each 100-hr increase in CPA = 1.79; 95% CI, 1.07-2.72). All these effects were dose related and most strongly linked to pool attendance before 6-7 years of age. Use of indoor chlorinated pools especially by young children interacts with atopic status to promote the development of childhood asthma. These findings further support the hypothesis implicating pool chlorine in the rise of childhood asthma in industrialized countries. Key words: aeroallergens, atopy, childhood asthma, chlorine, exercise-induced asthma, exhaled nitric oxide, nitrogen trichloride, swimming pool, total IgE, trichloramine.	35	94	2006	7	10.1289/ehp.8461	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Functional K(Ca)3.1 K+ channels are required for human lung mast cell migration. Background: Mast cell recruitment and activation are critical for the initiation and progression of inflammation and fibrosis. Mast cells infiltrate specific structures in many diseased tissues such as the airway smooth muscle (ASM) in asthma. This microlocalisation of mast cells is likely to be key to disease pathogenesis. Human lung mast cells (HLMC) express the Ca2+ activated K+ channel K(Ca)3.1 which modulates mediator release, and is proposed to facilitate the retraction of the cell body during migration of several cell types. A study was undertaken to test the hypothesis that blockade of K(Ca)3.1 would attenuate HLMC proliferation and migration. Methods: HLMC were isolated and purified from lung material resected for bronchial carcinoma. HLMC proliferation was assessed by cell counts at various time points following drug exposure. HLMC chemotaxis was assayed using standard Transwell chambers (8 mm pore size). Ion currents were measured using the single cell patch clamp technique. Results: K(Ca)3.1 blockade with triarylmethane-34 (TRAM-34) did not inhibit HLMC proliferation and clotrimazole had cytotoxic effects. In contrast, HLMC migration towards the chemokine CXCL10, the chemoattractant stem cell factor, and the supernatants from tumour necrosis factor a stimulated asthmatic ASM was markedly inhibited with both the non-selective K(Ca)3.1 blocker charybdotoxin and the highly specific K(Ca)3.1 blocker TRAM-34 in a dose dependent manner. Although K(Ca)3.1 blockade inhibits HLMC migration, K(Ca)3.1 is not opened by the chemotactic stimulus, suggesting that it must be involved downstream of the initial receptor-ligand interactions. Conclusions: Since modulation of K(Ca)3.1 can inhibit HLMC chemotaxis to diverse chemoattractants, the use of K(Ca)3.1 blockers such as TRAM-34 could provide new therapeutic strategies for mast cell mediated diseases such as asthma.. activated potassium channel| airway smooth-muscle| selective inhibitor| epithelial-cells| ion channels| bone-marrow| expression| proliferation| immunomodulation| infiltration.	OCT-2006	activated potassium channel| airway smooth-muscle| selective inhibitor| epithelial-cells| ion channels| bone-marrow| expression| proliferation| immunomodulation| infiltration	Cruse, G; Duffy, SM; Brightling, CE; Bradding, P	Functional K(Ca)3.1 K+ channels are required for human lung mast cell migration		THORAX		ACTIVATED POTASSIUM CHANNEL; AIRWAY SMOOTH-MUSCLE; SELECTIVE INHIBITOR; EPITHELIAL-CELLS; ION CHANNELS; BONE-MARROW; EXPRESSION; PROLIFERATION; IMMUNOMODULATION; INFILTRATION	Background: Mast cell recruitment and activation are critical for the initiation and progression of inflammation and fibrosis. Mast cells infiltrate specific structures in many diseased tissues such as the airway smooth muscle (ASM) in asthma. This microlocalisation of mast cells is likely to be key to disease pathogenesis. Human lung mast cells (HLMC) express the Ca2+ activated K+ channel K(Ca)3.1 which modulates mediator release, and is proposed to facilitate the retraction of the cell body during migration of several cell types. A study was undertaken to test the hypothesis that blockade of K(Ca)3.1 would attenuate HLMC proliferation and migration. Methods: HLMC were isolated and purified from lung material resected for bronchial carcinoma. HLMC proliferation was assessed by cell counts at various time points following drug exposure. HLMC chemotaxis was assayed using standard Transwell chambers (8 mm pore size). Ion currents were measured using the single cell patch clamp technique. Results: K(Ca)3.1 blockade with triarylmethane-34 (TRAM-34) did not inhibit HLMC proliferation and clotrimazole had cytotoxic effects. In contrast, HLMC migration towards the chemokine CXCL10, the chemoattractant stem cell factor, and the supernatants from tumour necrosis factor a stimulated asthmatic ASM was markedly inhibited with both the non-selective K(Ca)3.1 blocker charybdotoxin and the highly specific K(Ca)3.1 blocker TRAM-34 in a dose dependent manner. Although K(Ca)3.1 blockade inhibits HLMC migration, K(Ca)3.1 is not opened by the chemotactic stimulus, suggesting that it must be involved downstream of the initial receptor-ligand interactions. Conclusions: Since modulation of K(Ca)3.1 can inhibit HLMC chemotaxis to diverse chemoattractants, the use of K(Ca)3.1 blockers such as TRAM-34 could provide new therapeutic strategies for mast cell mediated diseases such as asthma.	35	94	2006	6	10.1136/thx.2006.060319	Respiratory System
Asthma exacerbations center dot 1: Epidemiology. Asthma exacerbations may be triggered by a number of atmospheric and domiciliary environmental factors as well as by those encountered in schools and workplaces. The majority of exacerbations, particularly in children, coincide with respiratory viral infections, most commonly rhinovirus. As most respiratory viruses and many aeroallergens appear in seasonal patterns, asthma exacerbations, particularly those requiring emergency treatment, show analogous seasonal cycles which differ in form in children and adults. While similar in form between the sexes, they differ in amplitude, with boys having higher risks of exacerbation in childhood and women in adult life. Simultaneous exposure of asthmatics with respiratory viral infections to allergens or air pollutants may significantly increase the risks of exacerbation. Access to and compliance with inhaled corticosteroid treatment is an important predictor of the likelihood of asthma exacerbations occurring, including those that occur during respiratory viral infections. Epidemiologically, the degree of asthma control achieved by asthmatics is an important predictor of the likelihood of disease exacerbation including respiratory failure, death, and health service consumption.. inhaled corticosteroids| respiratory-infections| industrial population| rhinovirus infections| hospital admissions| air-pollution| united-states| children| symptoms| illness.	AUG-2006	inhaled corticosteroids| respiratory-infections| industrial population| rhinovirus infections| hospital admissions| air-pollution| united-states| children| symptoms| illness	Johnston, NW; Sears, MR	Asthma exacerbations center dot 1: Epidemiology		THORAX		INHALED CORTICOSTEROIDS; RESPIRATORY-INFECTIONS; INDUSTRIAL POPULATION; RHINOVIRUS INFECTIONS; HOSPITAL ADMISSIONS; AIR-POLLUTION; UNITED-STATES; CHILDREN; SYMPTOMS; ILLNESS	Asthma exacerbations may be triggered by a number of atmospheric and domiciliary environmental factors as well as by those encountered in schools and workplaces. The majority of exacerbations, particularly in children, coincide with respiratory viral infections, most commonly rhinovirus. As most respiratory viruses and many aeroallergens appear in seasonal patterns, asthma exacerbations, particularly those requiring emergency treatment, show analogous seasonal cycles which differ in form in children and adults. While similar in form between the sexes, they differ in amplitude, with boys having higher risks of exacerbation in childhood and women in adult life. Simultaneous exposure of asthmatics with respiratory viral infections to allergens or air pollutants may significantly increase the risks of exacerbation. Access to and compliance with inhaled corticosteroid treatment is an important predictor of the likelihood of asthma exacerbations occurring, including those that occur during respiratory viral infections. Epidemiologically, the degree of asthma control achieved by asthmatics is an important predictor of the likelihood of disease exacerbation including respiratory failure, death, and health service consumption.	61	94	2006	7	10.1136/thx.2005.045161	Respiratory System
Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age. Background The prevalence of atopic dermatitis (AD) is increasing in Western societies. The hygiene hypothesis proposes that this is due to reduced exposure to environmental allergens and infections during early life. Objectives To examine factors associated with a diagnosis of AD at 3.5 years of age, especially those factors implicated by the hygiene hypothesis. Methods The Auckland Birthweight Collaborative study is a case-control study of risk factors for small for gestational age babies. Cases were born at term with birthweight <= 10th centile; controls were appropriate for gestational age, with birthweight > 10th centile. The infants were assessed at birth, 1 year and 3.5 years of age. Data were collected by parental interview and examination of the child. AD was defined as the presence of an itchy rash in the past 12 months with three or more of the following: history of flexural involvement; history of generally dry skin; history of atopic disease in parents or siblings; and visible flexural dermatitis as per photographic protocol. Statistical analyses took into account the disproportionate sampling of the study population. Results Analysis was restricted to European subjects. Eight hundred and seventy-one children were enrolled at birth, 744 (85.4%) participated at 1 year, and 550 (63.2%) at 3.5 years. AD was diagnosed in 87 (15.8%) children seen at 3.5 years. The prevalence of AD did not differ by birthweight. AD at 3.5 years was associated with raised serum IgE > 200 kU L-1, and wheezing, asthma, rash or eczema at 1 year. In multivariate analysis, adjusted for parental atopy and breastfeeding, AD at 3.5 years was associated with atopic disease in the parents: maternal atopy only, adjusted odds ratio (OR) 3.83, 95% confidence interval (CI) 1.20-12.23; paternal atopy only, adjusted OR 3.59, 95% CI 1.09-11.75; both parents atopic, adjusted OR 6.12, 95% CI 2.02-18.50. There was a higher risk of AD with longer duration of breastfeeding: < 6 months, adjusted OR 6.13, 95% CI 1.45-25.86; >= 6 months, adjusted OR 9.70, 95% CI 2.47-38.15 compared with never breastfed. These findings remained significant after adjusting for environmental factors and a personal history of atopy. AD at 3.5 years was associated with owning a cat at 3.5 years (adjusted OR 0.45, 95% CI 0.21-0.97) but not with owning a dog at 3.5 years, pets at 1 year, nor with older siblings. Furthermore, AD at 3.5 years was not associated with gender, socioeconomic status, maternal smoking, parity, damp, mould, immunizations, body mass index or antibiotic use in first year of life. Conclusions A personal and a parental history of atopic disease are risk factors for AD at 3.5 years. Duration of breastfeeding was associated with an increased risk of AD. No association was found with those factors implicated by the hygiene hypothesis. This study suggests that breastfeeding should not be recommended for the prevention of AD.. allergic diseases| atopic dermatitis| atopy| breastfeeding| eczema| hygiene hypothesis|allergic disease| hay-fever| childhood eczema| birth cohort| early-life| asthma| exposure| symptoms| infants| hygiene.	APR-2005	allergic diseases| atopic dermatitis| atopy| breastfeeding| eczema| hygiene hypothesis|allergic disease| hay-fever| childhood eczema| birth cohort| early-life| asthma| exposure| symptoms| infants| hygiene	Purvis, DJ; Thompson, JMD; Clark, PM; Robinson, E; Black, PN; Wild, CJ; Mitchell, EA	Risk factors for atopic dermatitis in New Zealand children at 3.5 years of age		BRITISH JOURNAL OF DERMATOLOGY	allergic diseases; atopic dermatitis; atopy; breastfeeding; eczema; hygiene hypothesis	ALLERGIC DISEASE; HAY-FEVER; CHILDHOOD ECZEMA; BIRTH COHORT; EARLY-LIFE; ASTHMA; EXPOSURE; SYMPTOMS; INFANTS; HYGIENE	Background The prevalence of atopic dermatitis (AD) is increasing in Western societies. The hygiene hypothesis proposes that this is due to reduced exposure to environmental allergens and infections during early life. Objectives To examine factors associated with a diagnosis of AD at 3.5 years of age, especially those factors implicated by the hygiene hypothesis. Methods The Auckland Birthweight Collaborative study is a case-control study of risk factors for small for gestational age babies. Cases were born at term with birthweight <= 10th centile; controls were appropriate for gestational age, with birthweight > 10th centile. The infants were assessed at birth, 1 year and 3.5 years of age. Data were collected by parental interview and examination of the child. AD was defined as the presence of an itchy rash in the past 12 months with three or more of the following: history of flexural involvement; history of generally dry skin; history of atopic disease in parents or siblings; and visible flexural dermatitis as per photographic protocol. Statistical analyses took into account the disproportionate sampling of the study population. Results Analysis was restricted to European subjects. Eight hundred and seventy-one children were enrolled at birth, 744 (85.4%) participated at 1 year, and 550 (63.2%) at 3.5 years. AD was diagnosed in 87 (15.8%) children seen at 3.5 years. The prevalence of AD did not differ by birthweight. AD at 3.5 years was associated with raised serum IgE > 200 kU L-1, and wheezing, asthma, rash or eczema at 1 year. In multivariate analysis, adjusted for parental atopy and breastfeeding, AD at 3.5 years was associated with atopic disease in the parents: maternal atopy only, adjusted odds ratio (OR) 3.83, 95% confidence interval (CI) 1.20-12.23; paternal atopy only, adjusted OR 3.59, 95% CI 1.09-11.75; both parents atopic, adjusted OR 6.12, 95% CI 2.02-18.50. There was a higher risk of AD with longer duration of breastfeeding: < 6 months, adjusted OR 6.13, 95% CI 1.45-25.86; >= 6 months, adjusted OR 9.70, 95% CI 2.47-38.15 compared with never breastfed. These findings remained significant after adjusting for environmental factors and a personal history of atopy. AD at 3.5 years was associated with owning a cat at 3.5 years (adjusted OR 0.45, 95% CI 0.21-0.97) but not with owning a dog at 3.5 years, pets at 1 year, nor with older siblings. Furthermore, AD at 3.5 years was not associated with gender, socioeconomic status, maternal smoking, parity, damp, mould, immunizations, body mass index or antibiotic use in first year of life. Conclusions A personal and a parental history of atopic disease are risk factors for AD at 3.5 years. Duration of breastfeeding was associated with an increased risk of AD. No association was found with those factors implicated by the hygiene hypothesis. This study suggests that breastfeeding should not be recommended for the prevention of AD.	34	94	2005	8	10.1111/j.1365-2133.2005.06540.x	Dermatology
Biofeedback treatment for asthma. Study objectives: We evaluated the effectiveness of heart rate variability (HRV) biofeedback as a complementary treatment for asthma. Patients: Ninety-four adult outpatient paid volunteers with asthma. Setting: The psychophysiology laboratory at The University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, and the private outpatient offices of participating asthma physicians. Interventions: The interventions were as follows: (1) a full protocol (ie, HRV biofeedback and abdominal breathing through pursed lips and prolonged exhalation); (2) HRV biofeedback alone; (3) placebo EEG biofeedback; and (4) a waiting list control. Design: Subjects were first prestabilized using controller medication and then were randomly assigned to experimental groups. Medication was titrated biweekly by blinded asthma specialists according to a protocol based on National Heart, Lung, and Blood Institute guidelines, according to symptoms, spirometry, and home peak flows. Measurements: Subjects recorded daily asthma symptoms and twice-daily peak expiratory flows. Spirometry was performed before and after each weekly treatment session under the HRV and placebo biofeedback conditions, and at triweekly assessment sessions under the waiting list condition. Oscillation resistance was measured approximately triweekly. Results: Compared with the two control groups, subjects in both of the two HRV biofeedback groups were prescribed less medication, with minimal differences between the two active treatments. Improvements averaged one full level of asthma severity. Measures from forced oscillation pneumography similarly showed improvement in pulmonary function. A placebo effect influenced an improvement in asthma symptoms, but not in pulmonary function. Groups did not differ in the occurrence of severe asthma flares. Conclusions: The results suggest that HRV biofeedback may prove to be a useful adjunct to asthma treatment and may help to reduce dependence on steroid medications. Further evaluation of this method is warranted.. airway resistance| alternative and complementary medicine| disease severity| heart rate variability| oscillation mechanics| psychology| self-regulation|heart-rate-variability| respiratory sinus arrhythmia| bone-mineral density| inhaled corticosteroids| controlled trial| impedance| therapy| complementary| relaxation| agonists.	AUG-2004	airway resistance| alternative and complementary medicine| disease severity| heart rate variability| oscillation mechanics| psychology| self-regulation|heart-rate-variability| respiratory sinus arrhythmia| bone-mineral density| inhaled corticosteroids| controlled trial| impedance| therapy| complementary| relaxation| agonists	Lehrer, PM; Vaschillo, E; Vaschillo, B; Lu, SE; Scardella, A; Siddique, M; Habib, RH	Biofeedback treatment for asthma		CHEST	airway resistance; alternative and complementary medicine; disease severity; heart rate variability; oscillation mechanics; psychology; self-regulation	HEART-RATE-VARIABILITY; RESPIRATORY SINUS ARRHYTHMIA; BONE-MINERAL DENSITY; INHALED CORTICOSTEROIDS; CONTROLLED TRIAL; IMPEDANCE; THERAPY; COMPLEMENTARY; RELAXATION; AGONISTS	Study objectives: We evaluated the effectiveness of heart rate variability (HRV) biofeedback as a complementary treatment for asthma. Patients: Ninety-four adult outpatient paid volunteers with asthma. Setting: The psychophysiology laboratory at The University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, and the private outpatient offices of participating asthma physicians. Interventions: The interventions were as follows: (1) a full protocol (ie, HRV biofeedback and abdominal breathing through pursed lips and prolonged exhalation); (2) HRV biofeedback alone; (3) placebo EEG biofeedback; and (4) a waiting list control. Design: Subjects were first prestabilized using controller medication and then were randomly assigned to experimental groups. Medication was titrated biweekly by blinded asthma specialists according to a protocol based on National Heart, Lung, and Blood Institute guidelines, according to symptoms, spirometry, and home peak flows. Measurements: Subjects recorded daily asthma symptoms and twice-daily peak expiratory flows. Spirometry was performed before and after each weekly treatment session under the HRV and placebo biofeedback conditions, and at triweekly assessment sessions under the waiting list condition. Oscillation resistance was measured approximately triweekly. Results: Compared with the two control groups, subjects in both of the two HRV biofeedback groups were prescribed less medication, with minimal differences between the two active treatments. Improvements averaged one full level of asthma severity. Measures from forced oscillation pneumography similarly showed improvement in pulmonary function. A placebo effect influenced an improvement in asthma symptoms, but not in pulmonary function. Groups did not differ in the occurrence of severe asthma flares. Conclusions: The results suggest that HRV biofeedback may prove to be a useful adjunct to asthma treatment and may help to reduce dependence on steroid medications. Further evaluation of this method is warranted.	35	94	2004	10	10.1378/chest.126.2.352	General & Internal Medicine; Respiratory System
The measurement of exhaled carbon monoxide in healthy smokers and non-smokers. The measurement of exhaled carbon monoxide (CO) level may provide an immediate, non-invasive method of assessing smoking status. The aims of this study were to use a portable CO monitor to compare the exhaled CO levels in established smokers and non-smokers. The exhaled CO levels were measured in 322 subjects (243 healthy smokers, 55 healthy non-smokers, 24 passive smokers) who applied to healthy stand during the spring student activity of Firat University in Elazig. Exhaled CO concentration was measured using the EC50 Smokerlyser. The mean exhaled CO level was 17.13 +/- 8.50 parts per million (ppm) for healthy smokers and 3.61 +/- 2.15 ppm for healthy non-smokers, and 5.20 +/- 3.38 ppm for passive smokers. There were significant positive correlation between CO levels and daily cigarette consumption, and CO levels and duration of smoking in healthy smokers (r = +0.550, P<0.001, r = +0.265, P<0.001, respectively. Spearman's test). When smokers and non-smokers were looked at as a whole, a cutoff of 6.5 ppm had a sensitivity of 90% and specificity of 83%. In conclusion, exhaled CO level provides an easy, an immediate way of assessing a subject's smoking status. (C) (C) 2004 Elsevier Ltd. All rights reserved.. exhaled carbon monoxide| smoking| passive smoking|expired-air| smoking cessation| passive smoking| cystic-fibrosis| breath| exposure| adolescents| asthma| trial.	JUN-2004	exhaled carbon monoxide| smoking| passive smoking|expired-air| smoking cessation| passive smoking| cystic-fibrosis| breath| exposure| adolescents| asthma| trial	Deveci, SE; Deveci, F; Acik, Y; Ozan, AT	The measurement of exhaled carbon monoxide in healthy smokers and non-smokers		RESPIRATORY MEDICINE	exhaled carbon monoxide; smoking; passive smoking	EXPIRED-AIR; SMOKING CESSATION; PASSIVE SMOKING; CYSTIC-FIBROSIS; BREATH; EXPOSURE; ADOLESCENTS; ASTHMA; TRIAL	The measurement of exhaled carbon monoxide (CO) level may provide an immediate, non-invasive method of assessing smoking status. The aims of this study were to use a portable CO monitor to compare the exhaled CO levels in established smokers and non-smokers. The exhaled CO levels were measured in 322 subjects (243 healthy smokers, 55 healthy non-smokers, 24 passive smokers) who applied to healthy stand during the spring student activity of Firat University in Elazig. Exhaled CO concentration was measured using the EC50 Smokerlyser. The mean exhaled CO level was 17.13 +/- 8.50 parts per million (ppm) for healthy smokers and 3.61 +/- 2.15 ppm for healthy non-smokers, and 5.20 +/- 3.38 ppm for passive smokers. There were significant positive correlation between CO levels and daily cigarette consumption, and CO levels and duration of smoking in healthy smokers (r = +0.550, P<0.001, r = +0.265, P<0.001, respectively. Spearman's test). When smokers and non-smokers were looked at as a whole, a cutoff of 6.5 ppm had a sensitivity of 90% and specificity of 83%. In conclusion, exhaled CO level provides an easy, an immediate way of assessing a subject's smoking status. (C) (C) 2004 Elsevier Ltd. All rights reserved.	33	94	2004	6	10.1016/j.rmed.2003.11.018	Cardiovascular System & Cardiology; Respiratory System
Trends in asthma, allergic rhinitis and eczema among Swedish conscripts from farming and non-farming environments. A nationwide study over three decades. Background Asthma and allergies are less common in children who have been raised in farming environments. Objectives To assess whether children who grow up in a farming environment have been protected against the general increase in atopic disorders in Sweden and whether other rural environments could also be protective. Method Linkage at an individual level of three national registers in Sweden: The Swedish Military Service Conscription Register (MSCR), the Register of the Total Population (RTP) and the Population and Housing Censuses (PHC). Asthma, allergic rhinitis and eczema at conscription were analysed in relation to area of residence, parental occupation, maternal age, family size and being the first born for 1 309 652 male conscripts in three successive cohorts born between 1952 and 1981. Results Allergic rhinitis and eczema displayed a continuous increase throughout the study period, whereas the rise in asthma mainly occurred in conscripts born after 1961. Farming environments and rural living already provided protection from allergic rhinitis in conscripts born during the 1950s, but the protective effect was greater in later cohorts. An inverse association was observed between farm living and asthma, but mainly in conscripts born after 1970. The adjusted risk ratios for asthma in conscripts from farming vs. non-farming families were 1.00 (95% CI 0.93-1.07), 0.94 (95% CI 0.88-1.01) and 0.85 (95% CI 0.79-0.91) in conscripts born in 1952-1961, 1962-1971 and 1972-1981, respectively. Rural living per se had no effect on the occurrence of asthma. Eczema was less common in rural areas, but the time trend was similar in urban and rural areas. Conclusions Our findings suggest that environmental changes affecting the whole of society have promoted an increase in asthma, allergic rhinitis and eczema in both farming and non-farming environments. A lower risk of allergic rhinitis in conscripts whose parents were involved in farming was observed in all birth cohorts, whereas the protective effect of growing up on a farm on the risk of asthma appears to be a fairly recent phenomenon.. allergic rhinitis| asthma| conscripts| eczema| epidemiology| farm environment| rural| time trend| urban|hay-fever| respiratory symptoms| atopic-dermatitis| young men| prevalence| children| sensitization| adults| diseases| exposure.	JAN-2004	allergic rhinitis| asthma| conscripts| eczema| epidemiology| farm environment| rural| time trend| urban|hay-fever| respiratory symptoms| atopic-dermatitis| young men| prevalence| children| sensitization| adults| diseases| exposure	Braback, L; Hjern, A; Rasmussen, F	Trends in asthma, allergic rhinitis and eczema among Swedish conscripts from farming and non-farming environments. A nationwide study over three decades		CLINICAL AND EXPERIMENTAL ALLERGY	allergic rhinitis; asthma; conscripts; eczema; epidemiology; farm environment; rural; time trend; urban	HAY-FEVER; RESPIRATORY SYMPTOMS; ATOPIC-DERMATITIS; YOUNG MEN; PREVALENCE; CHILDREN; SENSITIZATION; ADULTS; DISEASES; EXPOSURE	Background Asthma and allergies are less common in children who have been raised in farming environments. Objectives To assess whether children who grow up in a farming environment have been protected against the general increase in atopic disorders in Sweden and whether other rural environments could also be protective. Method Linkage at an individual level of three national registers in Sweden: The Swedish Military Service Conscription Register (MSCR), the Register of the Total Population (RTP) and the Population and Housing Censuses (PHC). Asthma, allergic rhinitis and eczema at conscription were analysed in relation to area of residence, parental occupation, maternal age, family size and being the first born for 1 309 652 male conscripts in three successive cohorts born between 1952 and 1981. Results Allergic rhinitis and eczema displayed a continuous increase throughout the study period, whereas the rise in asthma mainly occurred in conscripts born after 1961. Farming environments and rural living already provided protection from allergic rhinitis in conscripts born during the 1950s, but the protective effect was greater in later cohorts. An inverse association was observed between farm living and asthma, but mainly in conscripts born after 1970. The adjusted risk ratios for asthma in conscripts from farming vs. non-farming families were 1.00 (95% CI 0.93-1.07), 0.94 (95% CI 0.88-1.01) and 0.85 (95% CI 0.79-0.91) in conscripts born in 1952-1961, 1962-1971 and 1972-1981, respectively. Rural living per se had no effect on the occurrence of asthma. Eczema was less common in rural areas, but the time trend was similar in urban and rural areas. Conclusions Our findings suggest that environmental changes affecting the whole of society have promoted an increase in asthma, allergic rhinitis and eczema in both farming and non-farming environments. A lower risk of allergic rhinitis in conscripts whose parents were involved in farming was observed in all birth cohorts, whereas the protective effect of growing up on a farm on the risk of asthma appears to be a fairly recent phenomenon.	32	94	2004	6	10.1111/j.1365-2222.2004.01841.x	Allergy; Immunology
Children's respiratory morbidity prevalence in relation to air pollution in four Chinese cities. We examined respiratory health effects of long-term exposure to ambient air pollution in 7,621 schoolchildren residing in eight districts of four Chinese cities. The four cities exhibited wide between-city and within-city gradients in ambient levels of four size fractions of particulate matter [less than or equal to 2.5 pro in aerodynamic diameter (PM2.5), between 2.5 and 10 mum (PM10-2.5), less than or equal to 10 mum (PM10), and total suspended particulates (TSP)] and two gaseous pollutants (SO2 and NOx). Informed consent and written responses to questionnaires about children's personal, residential, and family information, as well as their health histories and status, were obtained with the help of the parents and the school personnel. We used a two-stage regression approach in data analyses. In the first-stage logistic regressions, we obtained logits of district-specific prevalence of wheeze, asthma, bronchitis, hospitalization for respiratory diseases, persistent cough, and persistent phlegm, adjusted for covariates representing personal, household, and family parameters. Some of these covariates were found to be risk factors of children's respiratory health, including being younger in the study group, being male, having been breast-fed, sharing bedrooms, sharing beds, room being smoky during cooking, eye irritation during cooking, parental smoking, and a history of parental asthma. In several of the second-stage variance-weighted linear regressions, we examined associations between district-specific adjusted prevalence rates and district-specific ambient levels of each pollutant. We found positive associations between morbidity prevalence and outdoor levels of PM of all size fractions, but the association appeared to be stronger for coarse particles (PM10-2.5). The results also present some evidence that ambient levels of NOx and SO2 were positively associated with children's respiratory symptoms, but the evidence for these two gaseous pollutants appeared to be weaker than that for the PM.. air pollution| children| china| particulate matter| respiratory health|long-term exposure| particulate matter| passive smoking| health| communities| california| particles| symptoms| pm10.	SEP-2002	air pollution| children| china| particulate matter| respiratory health|long-term exposure| particulate matter| passive smoking| health| communities| california| particles| symptoms| pm10	Zhang, JF; Hu, W; Wei, FS; Wu, GP; Korn, LR; Chapman, RS	Children's respiratory morbidity prevalence in relation to air pollution in four Chinese cities		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; children; China; particulate matter; respiratory health	LONG-TERM EXPOSURE; PARTICULATE MATTER; PASSIVE SMOKING; HEALTH; COMMUNITIES; CALIFORNIA; PARTICLES; SYMPTOMS; PM10	We examined respiratory health effects of long-term exposure to ambient air pollution in 7,621 schoolchildren residing in eight districts of four Chinese cities. The four cities exhibited wide between-city and within-city gradients in ambient levels of four size fractions of particulate matter [less than or equal to 2.5 pro in aerodynamic diameter (PM2.5), between 2.5 and 10 mum (PM10-2.5), less than or equal to 10 mum (PM10), and total suspended particulates (TSP)] and two gaseous pollutants (SO2 and NOx). Informed consent and written responses to questionnaires about children's personal, residential, and family information, as well as their health histories and status, were obtained with the help of the parents and the school personnel. We used a two-stage regression approach in data analyses. In the first-stage logistic regressions, we obtained logits of district-specific prevalence of wheeze, asthma, bronchitis, hospitalization for respiratory diseases, persistent cough, and persistent phlegm, adjusted for covariates representing personal, household, and family parameters. Some of these covariates were found to be risk factors of children's respiratory health, including being younger in the study group, being male, having been breast-fed, sharing bedrooms, sharing beds, room being smoky during cooking, eye irritation during cooking, parental smoking, and a history of parental asthma. In several of the second-stage variance-weighted linear regressions, we examined associations between district-specific adjusted prevalence rates and district-specific ambient levels of each pollutant. We found positive associations between morbidity prevalence and outdoor levels of PM of all size fractions, but the association appeared to be stronger for coarse particles (PM10-2.5). The results also present some evidence that ambient levels of NOx and SO2 were positively associated with children's respiratory symptoms, but the evidence for these two gaseous pollutants appeared to be weaker than that for the PM.	25	94	2002	7		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Endotoxins prevent murine IgE production,T(H)2 immune responses, and development of airway eosinophilia but not airway hyperreactivity. Background: Contact with immunomodulatory factors, such as LPS, in early infancy is associated with decreased allergen sensitization. Objective: We sought to study the effects of systemic or airway exposure with LPS on the development of allergen sensitization, eosinophilic airway inflammation, and increased in vivo airway reactivity (AR) in a mouse model. Methods: BALB/c mice were systemically sensitized with ovalbumin (OVA) plus adjuvant on days 1 and W and challenged through the airways with allergen on days 34 to 36. We performed measurement of OVA-specific IgE serum levels, in vitro T(H)2 cytokine production, differential cell counts in bronchoalveolar lavage fluids, and assessment of in vivo AR to inhaled methacholine by means of barometric whole-body plethysmography. Results: Systemic LPS administration before OVA sensitization reduced OVA-specific IgE serum levels (426 76 is 880 104 U/mL, P <.01), T(H)2 cytokine production by splenic mononuclear cells (IL-4: 0.08 +/- 0.01 vs 0.17 +/- 0.01 ng/mL; IL-5: 1.98 +/- 0.52 vs 4.11 +/- 0.54 ng/mL; P <.01), and extent of airway eosinophilia (total cell counts: 93 vs 376 x 10(3)/mL, eosinophils: 23% vs 51%; P <.01) compared with that in OVA-sensitized mice. Local LPS administration to sensitized mice before airway allergen challenges particularly induced IFN-gamma production by peribronchial lymph node cells in vitro (1718 +/- 315 vs 483 +/- 103 ng/mL, P <.01) associated with reduced airway eosinophilia compared with that seen in OVA-sensitized mice. Development of increased AR was not affected by systemic or local LPS exposure. Inhibitory effects of LPS on allergen sensitization and eosinophilic airway inflammation were inhibited bY administration of anti-IL-12 antibodies before LPS exposure. Conclusion: These data indicate that local and systemic application of LPS modulates systemic and local T(H)1/T(H)2 immune responses in a distinct but similarly IL-12-dependent mode.. mice| eosinophils| t(h)1/t(h)2 cells| cytokines| lipopolysaccharides|toll-like receptor-4| dendritic cells| bacterial lipopolysaccharide| inflammatory response| allergen challenge| sensitized mice| tnf-alpha| th2 cells| asthma| macrophages.	JUL-2002	mice| eosinophils| t(h)1/t(h)2 cells| cytokines| lipopolysaccharides|toll-like receptor-4| dendritic cells| bacterial lipopolysaccharide| inflammatory response| allergen challenge| sensitized mice| tnf-alpha| th2 cells| asthma| macrophages	Gerhold, K; Blumchen, K; Bock, A; Seib, C; Stock, P; Kallinich, T; Lohning, M; Wahn, U; Hamelmann, E	Endotoxins prevent murine IgE production,T(H)2 immune responses, and development of airway eosinophilia but not airway hyperreactivity		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	mice; eosinophils; T(H)1/T(H)2 cells; cytokines; lipopolysaccharides	TOLL-LIKE RECEPTOR-4; DENDRITIC CELLS; BACTERIAL LIPOPOLYSACCHARIDE; INFLAMMATORY RESPONSE; ALLERGEN CHALLENGE; SENSITIZED MICE; TNF-ALPHA; TH2 CELLS; ASTHMA; MACROPHAGES	Background: Contact with immunomodulatory factors, such as LPS, in early infancy is associated with decreased allergen sensitization. Objective: We sought to study the effects of systemic or airway exposure with LPS on the development of allergen sensitization, eosinophilic airway inflammation, and increased in vivo airway reactivity (AR) in a mouse model. Methods: BALB/c mice were systemically sensitized with ovalbumin (OVA) plus adjuvant on days 1 and W and challenged through the airways with allergen on days 34 to 36. We performed measurement of OVA-specific IgE serum levels, in vitro T(H)2 cytokine production, differential cell counts in bronchoalveolar lavage fluids, and assessment of in vivo AR to inhaled methacholine by means of barometric whole-body plethysmography. Results: Systemic LPS administration before OVA sensitization reduced OVA-specific IgE serum levels (426 76 is 880 104 U/mL, P <.01), T(H)2 cytokine production by splenic mononuclear cells (IL-4: 0.08 +/- 0.01 vs 0.17 +/- 0.01 ng/mL; IL-5: 1.98 +/- 0.52 vs 4.11 +/- 0.54 ng/mL; P <.01), and extent of airway eosinophilia (total cell counts: 93 vs 376 x 10(3)/mL, eosinophils: 23% vs 51%; P <.01) compared with that in OVA-sensitized mice. Local LPS administration to sensitized mice before airway allergen challenges particularly induced IFN-gamma production by peribronchial lymph node cells in vitro (1718 +/- 315 vs 483 +/- 103 ng/mL, P <.01) associated with reduced airway eosinophilia compared with that seen in OVA-sensitized mice. Development of increased AR was not affected by systemic or local LPS exposure. Inhibitory effects of LPS on allergen sensitization and eosinophilic airway inflammation were inhibited bY administration of anti-IL-12 antibodies before LPS exposure. Conclusion: These data indicate that local and systemic application of LPS modulates systemic and local T(H)1/T(H)2 immune responses in a distinct but similarly IL-12-dependent mode.	40	94	2002	7	10.1067/mai.2002.125831	Allergy; Immunology
Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease. Background Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen-induced T cell responses can provide information on cytokine production by allergen-reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non-specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN-gamma responses to allergens in atopic subjects. Objecgive To examine childhood polyclonal and allergen-induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease. Methods PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic). Results Atopic children had significantly reduced IFN-gamma and increased IL-4 and IL-5 but not IL13 production to SEB superantigen stimulation when compared with non-atopic children. HDM and RYE allergens stimulated significantly increased IFN-gamma, IL-5 and IL-13, while OVA stimulated significantly increased IFN-gamma production in atopic children. Conclusion We show that a polyclonal stimulus induces a reduced Th1 (IFN-gamma) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast, the allergen-induced cytokine responses in atopic children were associated with both increased Th1 (INF-gamma) and Th2 (IL-5 and IL-13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.. allergens| atopy| childhood| cytokines| house dust mite| interferon-gamma| interleukins-4/-5/-13| rye grass pollen| superantigens|blood mononuclear-cells| interferon-gamma production| messenger-rna expression| peripheral-blood| ifn-gamma| nonatopic children| interleukin-4 production| mite allergen| t-cells| asthma.	MAY-2002	allergens| atopy| childhood| cytokines| house dust mite| interferon-gamma| interleukins-4/-5/-13| rye grass pollen| superantigens|blood mononuclear-cells| interferon-gamma production| messenger-rna expression| peripheral-blood| ifn-gamma| nonatopic children| interleukin-4 production| mite allergen| t-cells| asthma	Smart, JM; Kemp, AS	Increased Th1 and Th2 allergen-induced cytokine responses in children with atopic disease		CLINICAL AND EXPERIMENTAL ALLERGY	allergens; atopy; childhood; cytokines; house dust mite; interferon-gamma; interleukins-4/-5/-13; rye grass pollen; superantigens	BLOOD MONONUCLEAR-CELLS; INTERFERON-GAMMA PRODUCTION; MESSENGER-RNA EXPRESSION; PERIPHERAL-BLOOD; IFN-GAMMA; NONATOPIC CHILDREN; INTERLEUKIN-4 PRODUCTION; MITE ALLERGEN; T-CELLS; ASTHMA	Background Polyclonal cytokine responses following stimulation of T cells with mitogens or superantigens provides information on cytokine production from a wide range of T cells. Alternatively allergen-induced T cell responses can provide information on cytokine production by allergen-reactive T cells. While there is evidence of increased Th2 and reduced Th1 cytokine production following T cell stimulation with non-specific mitogens and superantigens, the evidence that Th1 cytokine production to allergens is decreased in line with a postulated imbalance in Th1/Th2 responses is unclear, with studies finding decreased, no difference or increased IFN-gamma responses to allergens in atopic subjects. Objecgive To examine childhood polyclonal and allergen-induced cytokine responses in parallel to evaluate cytokine imbalances in childhood atopic disease. Methods PBMC cytokine responses were examined in response to a polyclonal stimulus, staphylococcal superantigen (SEB), in parallel with two inhalant allergens, house dust mite (HDM) and rye grass pollen (RYE), and an ingested allergen, ovalbumin (OVA), in (a) 35 healthy children (non-atopic) and (b) 36 children with atopic disease (asthma, eczema and/or rhinitis) (atopic). Results Atopic children had significantly reduced IFN-gamma and increased IL-4 and IL-5 but not IL13 production to SEB superantigen stimulation when compared with non-atopic children. HDM and RYE allergens stimulated significantly increased IFN-gamma, IL-5 and IL-13, while OVA stimulated significantly increased IFN-gamma production in atopic children. Conclusion We show that a polyclonal stimulus induces a reduced Th1 (IFN-gamma) and increased Th2 (IL-4 and IL-5) cytokine pattern. In contrast, the allergen-induced cytokine responses in atopic children were associated with both increased Th1 (INF-gamma) and Th2 (IL-5 and IL-13) cytokine production. The increased Th1 response to allergen is likely to reflect prior sensitization and indicates that increases in both Th1 and Th2 cytokine production to allergens exists concomitantly with a decreased Th1 response to a polyclonal stimulus in atopic children.	45	94	2002	7	10.1046/j.1365-2222.2002.01391.x	Allergy; Immunology
Association between ozone and hospitalization for acute respiratory diseases in children less than 2 years of age. To clarify the health effects of ozone exposure in young children, the authors studied the association between air pollution and hospital admissions for acute respiratory problems in children less than 2 years of age during the 15-year period from 1980 to 1994 in Toronto, Canada. The daily time series of admissions was adjusted for the influences of day of the week, season, and weather. A 35% (95% confidence interval: 19%, 52%) increase in the daily hospitalization rate for respiratory problems was associated with a 5-day moving average of the daily 1-hour maximum ozone concentration of 45 parts per billion, the May-August average value. The ozone effect persisted after adjustment for other ambient air pollutants or weather variables. Ozone was not associated with hospital admissions during the September-April period. Ambient ozone levels in the summertime should be considered a risk factor for respiratory problems in children less than 2 years of age.. air pollution| child| hospitalization| ozone| respiratory tract diseases|air-pollution| daily mortality| upper airways| admissions| asthma| particulate| toronto| emergency| illnesses| montreal.	MAR 1-2001	air pollution| child| hospitalization| ozone| respiratory tract diseases|air-pollution| daily mortality| upper airways| admissions| asthma| particulate| toronto| emergency| illnesses| montreal	Burnett, RT; Smith-Doiron, M; Stieb, D; Raizenne, ME; Brook, JR; Dales, RE; Leech, JA; Cakmak, S; Krewski, D	Association between ozone and hospitalization for acute respiratory diseases in children less than 2 years of age		AMERICAN JOURNAL OF EPIDEMIOLOGY	air pollution; child; hospitalization; ozone; respiratory tract diseases	AIR-POLLUTION; DAILY MORTALITY; UPPER AIRWAYS; ADMISSIONS; ASTHMA; PARTICULATE; TORONTO; EMERGENCY; ILLNESSES; MONTREAL	To clarify the health effects of ozone exposure in young children, the authors studied the association between air pollution and hospital admissions for acute respiratory problems in children less than 2 years of age during the 15-year period from 1980 to 1994 in Toronto, Canada. The daily time series of admissions was adjusted for the influences of day of the week, season, and weather. A 35% (95% confidence interval: 19%, 52%) increase in the daily hospitalization rate for respiratory problems was associated with a 5-day moving average of the daily 1-hour maximum ozone concentration of 45 parts per billion, the May-August average value. The ozone effect persisted after adjustment for other ambient air pollutants or weather variables. Ozone was not associated with hospital admissions during the September-April period. Ambient ozone levels in the summertime should be considered a risk factor for respiratory problems in children less than 2 years of age.	46	94	2001	9	10.1093/aje/153.5.444	Public, Environmental & Occupational Health
NAC Manchester Asthma and Allergy Study ((NAC)MAAS): risk factors for asthma and allergic disorders in adults. Background Asthma and atopic disorders are the most common chronic diseases in the developed countries. Knowledge of the risk factors for these disorders may facilitate the development of preventive strategies aimed at reducing prevalence rates. Objectives To investigate the risk factors for asthma and allergic diseases in a large number of adults who are the parents of children in the National Asthma Campaign Manchester Asthma and Allergy Study. Methods All pregnant women and their partners attending 'Booking' antenatal clinics were invited to take part in the study. Questionnaire data were collected including the history of asthma and other atopic diseases, pet ownership and smoking habits, and skin prick tests were performed. The prevalence of atopy and the risk factors for asthma and allergic disorders were investigated in all subjects who completed the questionnaire and underwent skin testing. Statistical analysis was carried out using logistic regression. Initially, risk factors were assessed by univariate analysis to see how each potential explanatory variable affected the probability of having allergic disease. Variables were then tested in a forward stepwise multivariate analysis. Results In 5687 adult subjects there was a very high (48.2%) prevalence of atopy, and 9.7% of subjects had a diagnosis of asthma. In a multivariate regression analysis sensitization to dust mite, cat, dog and mixed grasses were all independently associated with asthma. The odds ratios for current asthma increased with the increasing number of positive skin tests (any two allergens - OR 4.3, 95% CI 3.3-5.5; any three allergens - OR 7.0 95% CI 5.3-9.3; all four allergens - OR 10.4, 95% CI 7.7-14; P < 0.00001). Dog ownership (OR 1.31, 95% CI 1.10-1.57; P = 0.003) and current smoking (OR 1.36, 95% CI 1.15-1.62; P = 0.0004) were significantly and directly associated with 'asthma ever'. Thirteen per cent of participants reported a history of eczema. In the multivariate analysis the strongest independent associate of eczema was sensitization to dog (OR 1.37, 95% CI 1.14-1.63, P < 0.0001). Apart from dog, the strength of the association between sensitization to common allergens and eczema appeared to be much lower than in the case of asthma. The prevalence of hay fever was high (20.6%), and in the multivariate analysis the association between sensitization to pollen and hay fever was extremely strong (OR 13.6, 95% CI 11.3-16.3; P < 0.0001). Conclusions The results of the current study emphasize the importance of sensitization to indoor allergens in asthma. However, evidence of a possible direct role of allergen exposure in asthma causation remains unclear.. asthma| eczema| hay fever| allergens| skin prick tests|house-dust mite| respiratory health survey| childhood asthma| exposure| sensitization| children| population| cat| sensitivity| environment.	MAR-2001	asthma| eczema| hay fever| allergens| skin prick tests|house-dust mite| respiratory health survey| childhood asthma| exposure| sensitization| children| population| cat| sensitivity| environment	Simpson, BM; Custovic, A; Simpson, A; Hallam, CL; Walsh, D; Marolia, H; Campbell, J; Woodcock, A	NAC Manchester Asthma and Allergy Study ((NAC)MAAS): risk factors for asthma and allergic disorders in adults		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; eczema; hay fever; allergens; skin prick tests	HOUSE-DUST MITE; RESPIRATORY HEALTH SURVEY; CHILDHOOD ASTHMA; EXPOSURE; SENSITIZATION; CHILDREN; POPULATION; CAT; SENSITIVITY; ENVIRONMENT	Background Asthma and atopic disorders are the most common chronic diseases in the developed countries. Knowledge of the risk factors for these disorders may facilitate the development of preventive strategies aimed at reducing prevalence rates. Objectives To investigate the risk factors for asthma and allergic diseases in a large number of adults who are the parents of children in the National Asthma Campaign Manchester Asthma and Allergy Study. Methods All pregnant women and their partners attending 'Booking' antenatal clinics were invited to take part in the study. Questionnaire data were collected including the history of asthma and other atopic diseases, pet ownership and smoking habits, and skin prick tests were performed. The prevalence of atopy and the risk factors for asthma and allergic disorders were investigated in all subjects who completed the questionnaire and underwent skin testing. Statistical analysis was carried out using logistic regression. Initially, risk factors were assessed by univariate analysis to see how each potential explanatory variable affected the probability of having allergic disease. Variables were then tested in a forward stepwise multivariate analysis. Results In 5687 adult subjects there was a very high (48.2%) prevalence of atopy, and 9.7% of subjects had a diagnosis of asthma. In a multivariate regression analysis sensitization to dust mite, cat, dog and mixed grasses were all independently associated with asthma. The odds ratios for current asthma increased with the increasing number of positive skin tests (any two allergens - OR 4.3, 95% CI 3.3-5.5; any three allergens - OR 7.0 95% CI 5.3-9.3; all four allergens - OR 10.4, 95% CI 7.7-14; P < 0.00001). Dog ownership (OR 1.31, 95% CI 1.10-1.57; P = 0.003) and current smoking (OR 1.36, 95% CI 1.15-1.62; P = 0.0004) were significantly and directly associated with 'asthma ever'. Thirteen per cent of participants reported a history of eczema. In the multivariate analysis the strongest independent associate of eczema was sensitization to dog (OR 1.37, 95% CI 1.14-1.63, P < 0.0001). Apart from dog, the strength of the association between sensitization to common allergens and eczema appeared to be much lower than in the case of asthma. The prevalence of hay fever was high (20.6%), and in the multivariate analysis the association between sensitization to pollen and hay fever was extremely strong (OR 13.6, 95% CI 11.3-16.3; P < 0.0001). Conclusions The results of the current study emphasize the importance of sensitization to indoor allergens in asthma. However, evidence of a possible direct role of allergen exposure in asthma causation remains unclear.	30	94	2001	9	10.1046/j.1365-2222.2001.01050.x	Allergy; Immunology
The coming-of-age of the hygiene hypothesis. The hygiene hypothesis, as originally proposed, postulated an inverse relation between the incidence of infectious diseases in early life and the subsequent development of allergies and asthma. New evidence from epidemiological, biological and genetic studies has significantly enlarged the scope of the hypothesis. It now appears probable that environmental 'danger' signals regulate the pattern of immune responses in early life. Microbial burden in general, and not any single acute infectious illness, is the main source of these signals. The latter interact with a sensitive and complex receptor system, and genetic variations in this receptor system may be an important determinant of inherited susceptibility to asthma and allergies.. atopy| cd14| endotoxin| genetics| hygiene|hay-fever| allergic sensitization| early-life| asthma| atopy| children| exposure| association| endotoxin| risk.	2001	atopy| cd14| endotoxin| genetics| hygiene|hay-fever| allergic sensitization| early-life| asthma| atopy| children| exposure| association| endotoxin| risk	Martinez, FD	The coming-of-age of the hygiene hypothesis		RESPIRATORY RESEARCH	atopy; CD14; endotoxin; genetics; hygiene	HAY-FEVER; ALLERGIC SENSITIZATION; EARLY-LIFE; ASTHMA; ATOPY; CHILDREN; EXPOSURE; ASSOCIATION; ENDOTOXIN; RISK	The hygiene hypothesis, as originally proposed, postulated an inverse relation between the incidence of infectious diseases in early life and the subsequent development of allergies and asthma. New evidence from epidemiological, biological and genetic studies has significantly enlarged the scope of the hypothesis. It now appears probable that environmental 'danger' signals regulate the pattern of immune responses in early life. Microbial burden in general, and not any single acute infectious illness, is the main source of these signals. The latter interact with a sensitive and complex receptor system, and genetic variations in this receptor system may be an important determinant of inherited susceptibility to asthma and allergies.	29	94	2001	4	10.1186/rr48	Respiratory System
Incidence and determinants of IgE-mediated sensitization in apprentices - A prospective study. We investigated prospectively the incidence and determinants of work-related specific skin sensitization in a cohort of 769 apprentices, including 417 in animal health technology, 230 in pastry-making, and 122 in dental-hygiene technology. Subjects were recruited when starting exposure to laboratory animals, flour, or latex. A questionnaire and skin-prick tests with common and work-related allergens were administered on entry and at follow-up visits from 8 to 44 mo; information on number of hours of exposure to specific allergens was obtained. Among 769 apprentices, 698 attended greater than or equal to 1 follow-up visit. A total of 111 subjects developed specific sensitization over the study period. The incidence of work-related sensitization (per person-year) was 8.9% (95% CI 7.3 to 11.0%) in the animal-health program, 4.2% (95% CI 1.8 to 8.2%) in the pastry-making program, and 2.5% (95% CI = 0.7 to 4.3%) in the dental-hygiene program. In the animal health group, Cox regression analyses showed that atopy, nasal, and respiratory symptoms in the pollen season, and exposure assessed by the school attended or by duration of exposure to rodents were the most significant predictors of sensitization. In the dental-hygiene program, atopy and asthma were significant determinants. This study shows that: (1) an apprenticeship in animal-health technology carries a greater risk of developing specific sensitization than do apprenticeships in pastry-making and dental-hygiene; (2) atopy, respiratory symptoms in the pollen season, and number of hours in contact with rodents determine the risk of sensitization in apprentices in the animal health program.. exposure-response relationships| laboratory-animal workers| occupational asthma| general-population| latex| allergy| symptoms| atopy| rats| flour.	OCT-2000	exposure-response relationships| laboratory-animal workers| occupational asthma| general-population| latex| allergy| symptoms| atopy| rats| flour	Gautrin, D; Ghezzo, H; Infante-Rivard, C; Malo, JL	Incidence and determinants of IgE-mediated sensitization in apprentices - A prospective study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		EXPOSURE-RESPONSE RELATIONSHIPS; LABORATORY-ANIMAL WORKERS; OCCUPATIONAL ASTHMA; GENERAL-POPULATION; LATEX; ALLERGY; SYMPTOMS; ATOPY; RATS; FLOUR	We investigated prospectively the incidence and determinants of work-related specific skin sensitization in a cohort of 769 apprentices, including 417 in animal health technology, 230 in pastry-making, and 122 in dental-hygiene technology. Subjects were recruited when starting exposure to laboratory animals, flour, or latex. A questionnaire and skin-prick tests with common and work-related allergens were administered on entry and at follow-up visits from 8 to 44 mo; information on number of hours of exposure to specific allergens was obtained. Among 769 apprentices, 698 attended greater than or equal to 1 follow-up visit. A total of 111 subjects developed specific sensitization over the study period. The incidence of work-related sensitization (per person-year) was 8.9% (95% CI 7.3 to 11.0%) in the animal-health program, 4.2% (95% CI 1.8 to 8.2%) in the pastry-making program, and 2.5% (95% CI = 0.7 to 4.3%) in the dental-hygiene program. In the animal health group, Cox regression analyses showed that atopy, nasal, and respiratory symptoms in the pollen season, and exposure assessed by the school attended or by duration of exposure to rodents were the most significant predictors of sensitization. In the dental-hygiene program, atopy and asthma were significant determinants. This study shows that: (1) an apprenticeship in animal-health technology carries a greater risk of developing specific sensitization than do apprenticeships in pastry-making and dental-hygiene; (2) atopy, respiratory symptoms in the pollen season, and number of hours in contact with rodents determine the risk of sensitization in apprentices in the animal health program.	31	94	2000	7		General & Internal Medicine; Respiratory System
Airway remodeling is absent in CCR1(-/-) mice during chronic fungal allergic airway disease. Asthmatic-like reactions characterized by elevated IgE, Th2 cytokines, C-C chemokines, eosinophilic inflammation, and persistent airway hyperresponsiveness follow pulmonary exposure to the spores or conidia from Aspergillus fumigatus fungus in sensitized individuals. In addition to these features, subepithelial fibrosis and goblet cell hyperplasia characterizes fungal-induced allergic airway disease in mice. Because lung concentrations of macrophage inflammatory protein-1 alpha and RANTES were significantly elevated after A. fumigatus-sensitized mice received an intrapulmonary challenge with A. fumigatus spores or conidia, the present study addressed the role of their receptor, C-C chemokine receptor 1 (CCR1), in this model. A. fumigatus-sensitized CCR1 wild-type (+/+) and CCR1 knockout (-/-) mice exhibited similar increases in serum IgE and polymorphonuclear leukocyte numbers in the bronchoalveolar lavage, Airway hyperresponsiveness was prominent in both groups of mice at 30 days after an intrapulmonary challenge with A. fumigatus spores or conidia, However, whole lung levels of IFN-gamma were significantly higher whereas IL-4, IL-13, and Th2-inducible chemokines such as C10, eotaxin, and macrophage-derived chemokine were significantly lower in whole lung samples from CCR1(-/-) mice compared with CCR1(+/+) mice at 30 days after the conidia challenge. Likewise, significantly fewer goblet cells and less subepithelial fibrosis were observed around large airways in CCR1-/- mice at the same time after the conidia challenge. Thus, these findings demonstrate that CCR1 is a major contributor to the airway remodeling responses that arise from A. fumigatus-induced allergic airway disease.. human lung fibroblasts| bronchopulmonary aspergillosis| subepithelial fibrosis| chemokine receptors| th1 responses| murine model| host-defense| inflammation| asthma| hyperreactivity.	AUG 1-2000	human lung fibroblasts| bronchopulmonary aspergillosis| subepithelial fibrosis| chemokine receptors| th1 responses| murine model| host-defense| inflammation| asthma| hyperreactivity	Blease, K; Mehrad, B; Standiford, TJ; Lukacs, NW; Kunkel, SL; Chensue, SW; Lu, B; Gerard, CJ; Hogaboam, CM	Airway remodeling is absent in CCR1(-/-) mice during chronic fungal allergic airway disease		JOURNAL OF IMMUNOLOGY		HUMAN LUNG FIBROBLASTS; BRONCHOPULMONARY ASPERGILLOSIS; SUBEPITHELIAL FIBROSIS; CHEMOKINE RECEPTORS; TH1 RESPONSES; MURINE MODEL; HOST-DEFENSE; INFLAMMATION; ASTHMA; HYPERREACTIVITY	Asthmatic-like reactions characterized by elevated IgE, Th2 cytokines, C-C chemokines, eosinophilic inflammation, and persistent airway hyperresponsiveness follow pulmonary exposure to the spores or conidia from Aspergillus fumigatus fungus in sensitized individuals. In addition to these features, subepithelial fibrosis and goblet cell hyperplasia characterizes fungal-induced allergic airway disease in mice. Because lung concentrations of macrophage inflammatory protein-1 alpha and RANTES were significantly elevated after A. fumigatus-sensitized mice received an intrapulmonary challenge with A. fumigatus spores or conidia, the present study addressed the role of their receptor, C-C chemokine receptor 1 (CCR1), in this model. A. fumigatus-sensitized CCR1 wild-type (+/+) and CCR1 knockout (-/-) mice exhibited similar increases in serum IgE and polymorphonuclear leukocyte numbers in the bronchoalveolar lavage, Airway hyperresponsiveness was prominent in both groups of mice at 30 days after an intrapulmonary challenge with A. fumigatus spores or conidia, However, whole lung levels of IFN-gamma were significantly higher whereas IL-4, IL-13, and Th2-inducible chemokines such as C10, eotaxin, and macrophage-derived chemokine were significantly lower in whole lung samples from CCR1(-/-) mice compared with CCR1(+/+) mice at 30 days after the conidia challenge. Likewise, significantly fewer goblet cells and less subepithelial fibrosis were observed around large airways in CCR1-/- mice at the same time after the conidia challenge. Thus, these findings demonstrate that CCR1 is a major contributor to the airway remodeling responses that arise from A. fumigatus-induced allergic airway disease.	47	94	2000	9		Immunology
Colonization with superantigen-producing Staphylococcus aureus is associated with increased severity of atopic dermatitis. Background Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with colonization of the skin with Staphylococcus aureus known to produce toxins with superantigen (SAg) activity. Besides T-cell activation these toxins induce T-cell skin homing in vitro. This may contribute to the observed induction or enhancement of skin inflammation. Objective The aim of this study was to determine whether colonization with SAg-producing S. aureus isolates modulates the intensity of AD. If so, it was of interest whether this may be primarily due to the toxins' effects as SAgs or as allergens. Methods In AD patients, healthy controls, and atopic controls SAg production by S. aureus isolated from skin or mucous membranes was investigated and correlated to the severity of the disease. Total IgE, SAg-specific IgE, and T-cell activation and recirculation markers were analysed and correlated with SAg production. Results Fifty-seven percent of S. aureus strains isolated from AD patients produced SAgs. This frequency was higher compared to healthy controls (33%). SAg production by S. aureus was correlated with a significantly higher scoring of AD (SCORAD index, 58 +/- 19 in SAg-producing vs 41 +/- 7 in non-SAg-producing germs; P < 0.05). However, the severity of the disease was not associated with sensitization against the SAgs staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB). Furthermore, SAg production by S. aureus was inversely correlated with total IgE concentration (P < 0.05) and positively correlated with T-cell activation (as measured by HLA-DR and CD69 expression) and the expression of the T-cell skin homing phenotype cutaneous lymphocyte-associated antigen. Conclusion SAg production by S. aureus is suggested to be associated with an increased severity of atopic dermatitis. Since SAg production was found neither exclusively in AD patients nor in all patients, other pathogenic factors may be additionally effective.. atopic dermatitis| cutaneous lymphocyte-associated antigen| staphylococcus aureus| scorad| specific ige against sea/seb| staphylococcal enterotoxins| superantigen| t cell skin homing|shock syndrome toxin-1| lymphocyte-associated antigen| blood mononuclear-cells| human t-lymphocytes| bacterial superantigens| ige antibodies| up-regulation| skin| enterotoxins| expression.	JUL-2000	atopic dermatitis| cutaneous lymphocyte-associated antigen| staphylococcus aureus| scorad| specific ige against sea/seb| staphylococcal enterotoxins| superantigen| t cell skin homing|shock syndrome toxin-1| lymphocyte-associated antigen| blood mononuclear-cells| human t-lymphocytes| bacterial superantigens| ige antibodies| up-regulation| skin| enterotoxins| expression	Zollner, TM; Wichelhaus, TA; Hartung, A; Von Mallinckrodt, C; Wagner, TOF; Brade, V; Kaufmann, R	Colonization with superantigen-producing Staphylococcus aureus is associated with increased severity of atopic dermatitis		CLINICAL AND EXPERIMENTAL ALLERGY	atopic dermatitis; cutaneous lymphocyte-associated antigen; Staphylococcus aureus; SCORAD; specific IgE against SEA/SEB; staphylococcal enterotoxins; superantigen; T cell skin homing	SHOCK SYNDROME TOXIN-1; LYMPHOCYTE-ASSOCIATED ANTIGEN; BLOOD MONONUCLEAR-CELLS; HUMAN T-LYMPHOCYTES; BACTERIAL SUPERANTIGENS; IGE ANTIBODIES; UP-REGULATION; SKIN; ENTEROTOXINS; EXPRESSION	Background Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with colonization of the skin with Staphylococcus aureus known to produce toxins with superantigen (SAg) activity. Besides T-cell activation these toxins induce T-cell skin homing in vitro. This may contribute to the observed induction or enhancement of skin inflammation. Objective The aim of this study was to determine whether colonization with SAg-producing S. aureus isolates modulates the intensity of AD. If so, it was of interest whether this may be primarily due to the toxins' effects as SAgs or as allergens. Methods In AD patients, healthy controls, and atopic controls SAg production by S. aureus isolated from skin or mucous membranes was investigated and correlated to the severity of the disease. Total IgE, SAg-specific IgE, and T-cell activation and recirculation markers were analysed and correlated with SAg production. Results Fifty-seven percent of S. aureus strains isolated from AD patients produced SAgs. This frequency was higher compared to healthy controls (33%). SAg production by S. aureus was correlated with a significantly higher scoring of AD (SCORAD index, 58 +/- 19 in SAg-producing vs 41 +/- 7 in non-SAg-producing germs; P < 0.05). However, the severity of the disease was not associated with sensitization against the SAgs staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB). Furthermore, SAg production by S. aureus was inversely correlated with total IgE concentration (P < 0.05) and positively correlated with T-cell activation (as measured by HLA-DR and CD69 expression) and the expression of the T-cell skin homing phenotype cutaneous lymphocyte-associated antigen. Conclusion SAg production by S. aureus is suggested to be associated with an increased severity of atopic dermatitis. Since SAg production was found neither exclusively in AD patients nor in all patients, other pathogenic factors may be additionally effective.	39	94	2000	7		Allergy; Immunology
EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy. Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4months. There is no need to avoid introducing complementary foods beyond 4months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.. primary prevention| food allergy| children| eaaci| guidelines|randomized controlled-trial| hydrolyzed infant formulas| fish-oil supplementation| placebo-controlled trial| brief neonatal exposure| high-risk children| cows milk allergy| atopic disease| follow-up| birth cohort.	MAY-2014	primary prevention| food allergy| children| eaaci| guidelines|randomized controlled-trial| hydrolyzed infant formulas| fish-oil supplementation| placebo-controlled trial| brief neonatal exposure| high-risk children| cows milk allergy| atopic disease| follow-up| birth cohort	Muraro, A; Halken, S; Arshad, SH; Beyer, K; Dubois, AEJ; Du Toit, G; Eigenmann, PA; Grimshaw, KEC; Hoest, A; Lack, G; O'Mahony, L; Papadopoulos, NG; Panesar, S; Prescott, S; Roberts, G; de Silva, D; Venter, C; Verhasselt, V; Akdis, AC; Sheikh, A	EAACI Food Allergy and Anaphylaxis Guidelines. Primary prevention of food allergy		ALLERGY	primary prevention; food allergy; children; EAACI; guidelines	RANDOMIZED CONTROLLED-TRIAL; HYDROLYZED INFANT FORMULAS; FISH-OIL SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; BRIEF NEONATAL EXPOSURE; HIGH-RISK CHILDREN; COWS MILK ALLERGY; ATOPIC DISEASE; FOLLOW-UP; BIRTH COHORT	Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence-based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review. Based on this evidence, families can be provided with evidence-based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4-6months of life. If breastfeeding is insufficient or not possible, infants at high-risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4months. There is no need to avoid introducing complementary foods beyond 4months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.	97	93	2014	12	10.1111/all.12398	Allergy; Immunology
Lung-resident tissue macrophages generate Foxp3(+) regulatory T cells and promote airway tolerance. Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible T-reg cells [iT(reg) cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (Mempty sets), classical dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the attributes required to directly promote the development of Foxp3(+) iT(reg) cells is unclear. Here, we show that lung-resident tissue Mempty sets coexpress TGF-beta and retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and that their sampling of harmless airborne antigen and presentation to antigen-specific CD4 T cells resulted in the generation of Foxp3(+) T-reg cells. T-reg cell induction in this model depended on both TGF-beta and retinoic acid. Transfer of the antigen-pulsed tissue Mempty sets into the airways correspondingly prevented the development of asthmatic lung inflammation upon subsequent challenge with antigen. Moreover, exposure of lung tissue Mempty sets to allergens suppressed their ability to generate iT(reg) cells coincident with blocking airway tolerance. Suppression of T-reg cell generation required proteases and TLR-mediated signals. Therefore, lung-resident tissue Mempty sets have regulatory functions, and strategies to target these cells might hold promise for prevention or treatment of allergic asthma.. house-dust mite| alveolar macrophages| dendritic cells| retinoic-acid| allergic inflammation| inhaled antigen| tgf-beta| aspergillus-fumigatus| immune-response| flow-cytometry.	APR 8-2013	house-dust mite| alveolar macrophages| dendritic cells| retinoic-acid| allergic inflammation| inhaled antigen| tgf-beta| aspergillus-fumigatus| immune-response| flow-cytometry	Soroosh, P; Doherty, TA; Duan, W; Mehta, AK; Choi, H; Adams, YF; Mikulski, Z; Khorram, N; Rosenthal, P; Broide, DH; Croft, M	Lung-resident tissue macrophages generate Foxp3(+) regulatory T cells and promote airway tolerance		JOURNAL OF EXPERIMENTAL MEDICINE		HOUSE-DUST MITE; ALVEOLAR MACROPHAGES; DENDRITIC CELLS; RETINOIC-ACID; ALLERGIC INFLAMMATION; INHALED ANTIGEN; TGF-BETA; ASPERGILLUS-FUMIGATUS; IMMUNE-RESPONSE; FLOW-CYTOMETRY	Airway tolerance is the usual outcome of inhalation of harmless antigens. Although T cell deletion and anergy are likely components of tolerogenic mechanisms in the lung, increasing evidence indicates that antigen-specific regulatory T cells (inducible T-reg cells [iT(reg) cells]) that express Foxp3 are also critical. Several lung antigen-presenting cells have been suggested to contribute to tolerance, including alveolar macrophages (Mempty sets), classical dendritic cells (DCs), and plasmacytoid DCs, but whether these possess the attributes required to directly promote the development of Foxp3(+) iT(reg) cells is unclear. Here, we show that lung-resident tissue Mempty sets coexpress TGF-beta and retinal dehydrogenases (RALDH1 and RALDH 2) under steady-state conditions and that their sampling of harmless airborne antigen and presentation to antigen-specific CD4 T cells resulted in the generation of Foxp3(+) T-reg cells. T-reg cell induction in this model depended on both TGF-beta and retinoic acid. Transfer of the antigen-pulsed tissue Mempty sets into the airways correspondingly prevented the development of asthmatic lung inflammation upon subsequent challenge with antigen. Moreover, exposure of lung tissue Mempty sets to allergens suppressed their ability to generate iT(reg) cells coincident with blocking airway tolerance. Suppression of T-reg cell generation required proteases and TLR-mediated signals. Therefore, lung-resident tissue Mempty sets have regulatory functions, and strategies to target these cells might hold promise for prevention or treatment of allergic asthma.	64	93	2013	14	10.1084/jem.20121849	Immunology; Research & Experimental Medicine
A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. Background: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. Objective: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. Method: Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). Results: Three loci reached genome-wide significance for either phenotype. The HLAvariant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P-grass = 1.6 x 10(-9); P-AR = 8.0 x 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P-grass = 9.4 x 10(-9); P-AR = 3.8 x 10(-8))(.) The third genome-wide significant variant was rs17513503 (P-grass = 1.2 x 10(-8); PAR = 7.4 x 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. Conclusions: This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. (J Allergy Clin Immunol 2011;128:996-1005.). hay fever| ige sensitization to grass| hygiene hypothesis| older siblings| gene-environment interaction| genome-wide association study| european community respiratory health survey| british 1958 birth cohort| northern finland birth cohort of 1966| swiss study on air pollution and lung disease in adults|respiratory-health-survey| hay-fever| environment interaction| filaggrin mutations| childhood eczema| chromosome 11q13| asthma| cohort| exposure| diseases.	NOV-2011	hay fever| ige sensitization to grass| hygiene hypothesis| older siblings| gene-environment interaction| genome-wide association study| european community respiratory health survey| british 1958 birth cohort| northern finland birth cohort of 1966| swiss study on air pollution and lung disease in adults|respiratory-health-survey| hay-fever| environment interaction| filaggrin mutations| childhood eczema| chromosome 11q13| asthma| cohort| exposure| diseases	Ramasamy, A; Curjuric, I; Coin, LJ; Kumar, A; McArdle, WL; Imboden, M; Leynaert, B; Kogevinas, M; Schmid-Grendelmeier, P; Pekkanen, J; Wjst, M; Bircher, AJ; Sovio, U; Rochat, T; Hartikainen, AL; Balding, DJ; Jarvelin, MR; Probst-Hensch, N; Strachan, DP; Jarvis, DL	A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Hay fever; IgE sensitization to grass; hygiene hypothesis; older siblings; gene-environment interaction; genome-wide association study; European Community Respiratory Health Survey; British 1958 Birth Cohort; Northern Finland Birth Cohort of 1966; Swiss Study on Air Pollution and Lung Disease in Adults	RESPIRATORY-HEALTH-SURVEY; HAY-FEVER; ENVIRONMENT INTERACTION; FILAGGRIN MUTATIONS; CHILDHOOD ECZEMA; CHROMOSOME 11Q13; ASTHMA; COHORT; EXPOSURE; DISEASES	Background: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear. Objective: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings. Method: Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects). Results: Three loci reached genome-wide significance for either phenotype. The HLAvariant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P-grass = 1.6 x 10(-9); P-AR = 8.0 x 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P-grass = 9.4 x 10(-9); P-AR = 3.8 x 10(-8))(.) The third genome-wide significant variant was rs17513503 (P-grass = 1.2 x 10(-8); PAR = 7.4 x 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype. Conclusions: This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. (J Allergy Clin Immunol 2011;128:996-1005.)	38	93	2011	10	10.1016/j.jaci.2011.08.030	Allergy; Immunology
Distribution of heavy metals in road dust along an urban-rural gradient in Massachusetts. Human exposures to particulate matter emitted from on-road motor vehicles include complex mixtures of metals from tires, brakes, parts wear and resuspended road dust. The aim of this study was to assess road dust for metals associated with motor vehicle traffic, particularly those metals coming from brake and tire wears. We hypothesized that the road dust would show significant difference in both composition and concentration by traffic type, road class and by location. X-ray fluorescence (XRF) analyses of 115 parked car tires showed Zn and Ca were likely associated with tire wear dust. XRF results of three used brake pads indicated high concentrations of Fe, Ti, Cu, Ba, Mo and Zr. To assess heavy metal exposures associated with tires and brake wear adjacent to roads of varying traffic and functional classes, 85 samples of road dust were collected from road surfaces adjacent to the curb and analyzed by XRF. Median concentrations for Fe. Ca and K were greater than Ti (1619 ppm), with concentration ratios of Fe: Ca: K: Ti [16:5:3:1]. Cumulative frequency distribution graphs showed distribution of Fe, Ba, Cu, and Mo were similar regardless of road traffic rating. However, Zn, Ti, and Zr varied significantly (p < 0.05) with traffic ratings of roadways (heavy > moderate > low traffic). Fe, Ba, Cu, and Mo also had similar distributions regardless of road class while composition of Zn, Ti, and Zr varied significantly across road class (p < 0.05) (Major roads > Minor roads > highway). In comparing urban road dust to rural road dust, we observed Fe, Ca, K, and Ti were significantly greater in urban road dust (p < 0.05). In urban road dust the Fe: Ca: K: Ti relationship with median Ti of 2216 ppm was 12: 6: 3.5: 1. These results indicate that roadway dust may be important sources of metals for runoff water and localized resuspended particulate matter. (C) 2010 Elsevier Ltd. All rights reserved.. heavy metal| road dust| tire wear| brake wear| traffic-related emissions|particulate matter| hong-kong| particle resuspension| source profiles| air-pollution| street dusts| contamination| asthma| soils| emissions.	APR-2011	heavy metal| road dust| tire wear| brake wear| traffic-related emissions|particulate matter| hong-kong| particle resuspension| source profiles| air-pollution| street dusts| contamination| asthma| soils| emissions	Apeagyei, E; Bank, MS; Spengler, JD	Distribution of heavy metals in road dust along an urban-rural gradient in Massachusetts		ATMOSPHERIC ENVIRONMENT	Heavy metal; Road dust; Tire wear; Brake wear; Traffic-related emissions	PARTICULATE MATTER; HONG-KONG; PARTICLE RESUSPENSION; SOURCE PROFILES; AIR-POLLUTION; STREET DUSTS; CONTAMINATION; ASTHMA; SOILS; EMISSIONS	Human exposures to particulate matter emitted from on-road motor vehicles include complex mixtures of metals from tires, brakes, parts wear and resuspended road dust. The aim of this study was to assess road dust for metals associated with motor vehicle traffic, particularly those metals coming from brake and tire wears. We hypothesized that the road dust would show significant difference in both composition and concentration by traffic type, road class and by location. X-ray fluorescence (XRF) analyses of 115 parked car tires showed Zn and Ca were likely associated with tire wear dust. XRF results of three used brake pads indicated high concentrations of Fe, Ti, Cu, Ba, Mo and Zr. To assess heavy metal exposures associated with tires and brake wear adjacent to roads of varying traffic and functional classes, 85 samples of road dust were collected from road surfaces adjacent to the curb and analyzed by XRF. Median concentrations for Fe. Ca and K were greater than Ti (1619 ppm), with concentration ratios of Fe: Ca: K: Ti [16:5:3:1]. Cumulative frequency distribution graphs showed distribution of Fe, Ba, Cu, and Mo were similar regardless of road traffic rating. However, Zn, Ti, and Zr varied significantly (p < 0.05) with traffic ratings of roadways (heavy > moderate > low traffic). Fe, Ba, Cu, and Mo also had similar distributions regardless of road class while composition of Zn, Ti, and Zr varied significantly across road class (p < 0.05) (Major roads > Minor roads > highway). In comparing urban road dust to rural road dust, we observed Fe, Ca, K, and Ti were significantly greater in urban road dust (p < 0.05). In urban road dust the Fe: Ca: K: Ti relationship with median Ti of 2216 ppm was 12: 6: 3.5: 1. These results indicate that roadway dust may be important sources of metals for runoff water and localized resuspended particulate matter. (C) 2010 Elsevier Ltd. All rights reserved.	42	93	2011	14	10.1016/j.atmosenv.2010.11.015	Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
Influence of indoor factors in dwellings on the development of childhood asthma. Asthma has become the most common, childhood chronic disease in the industrialized world, and it is also increasing in developing regions. There are huge differences in the prevalence of childhood asthma across countries and continents, and there is no doubt that the prevalence of asthma was strongly increasing during the past decades worldwide. Asthma, as a complex disease, has a broad spectrum of potential determinants ranging from genetics to life style and environmental factors. Environmental factors are likely to be important in explaining the regional differences and the overall increasing trend towards asthma's prevalence. Among the environmental conditions, indoor factors are of particular interest because people spend more than 80% of their time indoors globally. Increasing prices for oil, gas and other sources of primary energy will further lead to better insulation of homes, and ultimately to reduced energy costs. This will decrease air exchange rates and will lower the dilution of indoor air mass with ambient air. Indoor air quality and potential health effects will therefore be an area for future research and for gaining a better understanding of asthma epidemics. This strategic review will summarize the current knowledge of the effects of a broad spectrum of indoor factors on the development of asthma in childhood in Western countries based on epidemiological studies. In conclusion, several epidemiological studies point out, that indoor factors might cause asthma in childhood. Stronger and more consistent findings are seen when exposure to these indoor factors is assessed by surrogates for the source of the actual toxicants. Measurement-based exposure assessments for several indoor factors are less common than using surrogates of the exposure. These studies, however, mainly showed heterogeneous results. The most consistent finding for an induction of asthma in childhood is related to exposure to environmental tobacco smoke, to living in homes close to busy roads, and in damp homes where are visible moulds at home. The causing agents of the increased risk of living in damp homes remained uncertain and needs clarification. Exposure to pet-derived allergens and house dust mites are very commonly investigated and thought to be related to asthma onset. The epidemiological evidence is not sufficient to recommend avoidance measures against pet and dust mites as preventive activities against allergies. More research is also needed to clarify the potential risk for exposure to volatile and semi-volatile organic compounds due to renovation activities, phthalates and chlorine chemicals due to cleaning. (C) 2010 Elsevier GmbH. All rights reserved.. asthma| children| incidence| indoor factor| epidemiology|polycyclic aromatic-hydrocarbons| volatile organic-compounds| house-dust mite| environmental tobacco-smoke| nitrogen-dioxide exposure| childrens respiratory health| outdoor air-pollution| school-age-children| 1st 5 years| young-children.	JAN-2011	asthma| children| incidence| indoor factor| epidemiology|polycyclic aromatic-hydrocarbons| volatile organic-compounds| house-dust mite| environmental tobacco-smoke| nitrogen-dioxide exposure| childrens respiratory health| outdoor air-pollution| school-age-children| 1st 5 years| young-children	Heinrich, J	Influence of indoor factors in dwellings on the development of childhood asthma		INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH	Asthma; Children; Incidence; Indoor factor; Epidemiology	POLYCYCLIC AROMATIC-HYDROCARBONS; VOLATILE ORGANIC-COMPOUNDS; HOUSE-DUST MITE; ENVIRONMENTAL TOBACCO-SMOKE; NITROGEN-DIOXIDE EXPOSURE; CHILDRENS RESPIRATORY HEALTH; OUTDOOR AIR-POLLUTION; SCHOOL-AGE-CHILDREN; 1ST 5 YEARS; YOUNG-CHILDREN	Asthma has become the most common, childhood chronic disease in the industrialized world, and it is also increasing in developing regions. There are huge differences in the prevalence of childhood asthma across countries and continents, and there is no doubt that the prevalence of asthma was strongly increasing during the past decades worldwide. Asthma, as a complex disease, has a broad spectrum of potential determinants ranging from genetics to life style and environmental factors. Environmental factors are likely to be important in explaining the regional differences and the overall increasing trend towards asthma's prevalence. Among the environmental conditions, indoor factors are of particular interest because people spend more than 80% of their time indoors globally. Increasing prices for oil, gas and other sources of primary energy will further lead to better insulation of homes, and ultimately to reduced energy costs. This will decrease air exchange rates and will lower the dilution of indoor air mass with ambient air. Indoor air quality and potential health effects will therefore be an area for future research and for gaining a better understanding of asthma epidemics. This strategic review will summarize the current knowledge of the effects of a broad spectrum of indoor factors on the development of asthma in childhood in Western countries based on epidemiological studies. In conclusion, several epidemiological studies point out, that indoor factors might cause asthma in childhood. Stronger and more consistent findings are seen when exposure to these indoor factors is assessed by surrogates for the source of the actual toxicants. Measurement-based exposure assessments for several indoor factors are less common than using surrogates of the exposure. These studies, however, mainly showed heterogeneous results. The most consistent finding for an induction of asthma in childhood is related to exposure to environmental tobacco smoke, to living in homes close to busy roads, and in damp homes where are visible moulds at home. The causing agents of the increased risk of living in damp homes remained uncertain and needs clarification. Exposure to pet-derived allergens and house dust mites are very commonly investigated and thought to be related to asthma onset. The epidemiological evidence is not sufficient to recommend avoidance measures against pet and dust mites as preventive activities against allergies. More research is also needed to clarify the potential risk for exposure to volatile and semi-volatile organic compounds due to renovation activities, phthalates and chlorine chemicals due to cleaning. (C) 2010 Elsevier GmbH. All rights reserved.	228	93	2011	25	10.1016/j.ijheh.2010.08.009	Public, Environmental & Occupational Health; Infectious Diseases
GA(2)LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma. This pocket guide is the result of a consensus reached during several GA(2)LEN and EAACI meetings. The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of immunotherapy in allergic rhinoconjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions of practitioners in Europe, including 'practising allergists', general practitioners and any other physicians with special interest in allergen-specific immunotherapy (SIT). It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1998 EAACI position paper, the 1998 WHO Position Paper on SIT and the 2001 Allergic Rhinitis and its Impact on Asthma (ARIA). It is also based on the ARIA update 2008 (prepared in collaboration with GA(2)LEN), the 'Sub-lingual Immunotherapy: WAO Position Paper 2009' (from the World Allergy Organisation) and the Methodology paper of ARIA. The recommendations cover patient selection, allergen extract to be used, route of administration of SIT (in particular, sublingual and subcutaneous immunotherapy), and necessary precautions to be followed in using SIT.. allergen| european academy of allergy and immunology (eaaci)| global allergy and asthma european network (ga(2)len)| immunotherapy| subcutaneous| sublingual|house-dust mite| dermatophagoides-pteronyssinus extract| consort statement| grass-pollen| follow-up| sublingual immunotherapy| randomized-trials| clinical-efficacy| double-blind| 2008 update.	DEC-2010	allergen| european academy of allergy and immunology (eaaci)| global allergy and asthma european network (ga(2)len)| immunotherapy| subcutaneous| sublingual|house-dust mite| dermatophagoides-pteronyssinus extract| consort statement| grass-pollen| follow-up| sublingual immunotherapy| randomized-trials| clinical-efficacy| double-blind| 2008 update	Zuberbier, T; Bachert, C; Bousquet, PJ; Passalacqua, G; Canonica, GW; Merk, H; Worm, M; Wahn, U; Bousquet, J	GA(2)LEN/EAACI pocket guide for allergen-specific immunotherapy for allergic rhinitis and asthma		ALLERGY	allergen; European Academy of Allergy and Immunology (EAACI); Global Allergy and Asthma European Network (GA(2)LEN); immunotherapy; subcutaneous; sublingual	HOUSE-DUST MITE; DERMATOPHAGOIDES-PTERONYSSINUS EXTRACT; CONSORT STATEMENT; GRASS-POLLEN; FOLLOW-UP; SUBLINGUAL IMMUNOTHERAPY; RANDOMIZED-TRIALS; CLINICAL-EFFICACY; DOUBLE-BLIND; 2008 UPDATE	This pocket guide is the result of a consensus reached during several GA(2)LEN and EAACI meetings. The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of immunotherapy in allergic rhinoconjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions of practitioners in Europe, including 'practising allergists', general practitioners and any other physicians with special interest in allergen-specific immunotherapy (SIT). It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1998 EAACI position paper, the 1998 WHO Position Paper on SIT and the 2001 Allergic Rhinitis and its Impact on Asthma (ARIA). It is also based on the ARIA update 2008 (prepared in collaboration with GA(2)LEN), the 'Sub-lingual Immunotherapy: WAO Position Paper 2009' (from the World Allergy Organisation) and the Methodology paper of ARIA. The recommendations cover patient selection, allergen extract to be used, route of administration of SIT (in particular, sublingual and subcutaneous immunotherapy), and necessary precautions to be followed in using SIT.	27	93	2010	6	10.1111/j.1398-9995.2010.02474.x	Allergy; Immunology
A new look at the pathogenesis of asthma. Asthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.. allergen| asthma| inflammation| remodelling| t-cell| virus infection|airway epithelial-cells| resolution computed-tomography| thymic stromal lymphopoietin| smooth-muscle| childhood asthma| bronchial hyperresponsiveness| barrier function| lung-function| persistent asthma| atopic asthma.	APR 10-2010	allergen| asthma| inflammation| remodelling| t-cell| virus infection|airway epithelial-cells| resolution computed-tomography| thymic stromal lymphopoietin| smooth-muscle| childhood asthma| bronchial hyperresponsiveness| barrier function| lung-function| persistent asthma| atopic asthma	Holgate, ST; Arshad, HS; Roberts, GC; Howarth, PH; Thurner, P; Davies, DE	A new look at the pathogenesis of asthma		CLINICAL SCIENCE	allergen; asthma; inflammation; remodelling; T-cell; virus infection	AIRWAY EPITHELIAL-CELLS; RESOLUTION COMPUTED-TOMOGRAPHY; THYMIC STROMAL LYMPHOPOIETIN; SMOOTH-MUSCLE; CHILDHOOD ASTHMA; BRONCHIAL HYPERRESPONSIVENESS; BARRIER FUNCTION; LUNG-FUNCTION; PERSISTENT ASTHMA; ATOPIC ASTHMA	Asthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.	105	93	2010	12	10.1042/CS20090474	Research & Experimental Medicine
Genetics of allergic disease. Allergic diseases are complex genetic diseases resulting from the effect of multiple genetic and interacting environmental factors on their pathophysiology. Recent years have seen considerable progress in unraveling the contribution of these factors to an individual subject's susceptibility to, subsequent development of, and severity of disease. This has resulted in increasing insight into novel areas of allergic disease pathophysiology, for example the significant role played by locally acting tissue susceptibility factors like epithelial/epidermal barrier function and remodeling, such as filaggrin, ADAM33, and GSDML/ORMDL3, in patients with atopic dermatitis and asthma. Furthermore, studies of gene-environment interactions and Mendelian randomization approaches have led to increased insight into the importance of environmental triggers for allergic disease. Studies of the timing of action of genetic variants in determining disease susceptibility have highlighted the importance of in utero development and early life in determining susceptibility to allergic disease. In the future, genetic discoveries in allergic disease will potentially lead to better endophenotyping, prognostication, prediction of treatment response, and insights into molecular pathways to develop more targeted therapy for these conditions. (J Allergy Clin Immunol 2010;125:S81-94.). heritability| genetics| genetic testing| pharmacogenetics| epigenetics|genome-wide association| diisocyanate-induced asthma| severe persistent asthma| improved lung-function| of-function mutations| dust-mite exposure| hyper-ige syndrome| childhood asthma| filaggrin mutations| atopic-dermatitis.	FEB-2010	heritability| genetics| genetic testing| pharmacogenetics| epigenetics|genome-wide association| diisocyanate-induced asthma| severe persistent asthma| improved lung-function| of-function mutations| dust-mite exposure| hyper-ige syndrome| childhood asthma| filaggrin mutations| atopic-dermatitis	Holloway, JW; Yang, IA; Holgate, ST	Genetics of allergic disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Heritability; genetics; genetic testing; pharmacogenetics; epigenetics	GENOME-WIDE ASSOCIATION; DIISOCYANATE-INDUCED ASTHMA; SEVERE PERSISTENT ASTHMA; IMPROVED LUNG-FUNCTION; OF-FUNCTION MUTATIONS; DUST-MITE EXPOSURE; HYPER-IGE SYNDROME; CHILDHOOD ASTHMA; FILAGGRIN MUTATIONS; ATOPIC-DERMATITIS	Allergic diseases are complex genetic diseases resulting from the effect of multiple genetic and interacting environmental factors on their pathophysiology. Recent years have seen considerable progress in unraveling the contribution of these factors to an individual subject's susceptibility to, subsequent development of, and severity of disease. This has resulted in increasing insight into novel areas of allergic disease pathophysiology, for example the significant role played by locally acting tissue susceptibility factors like epithelial/epidermal barrier function and remodeling, such as filaggrin, ADAM33, and GSDML/ORMDL3, in patients with atopic dermatitis and asthma. Furthermore, studies of gene-environment interactions and Mendelian randomization approaches have led to increased insight into the importance of environmental triggers for allergic disease. Studies of the timing of action of genetic variants in determining disease susceptibility have highlighted the importance of in utero development and early life in determining susceptibility to allergic disease. In the future, genetic discoveries in allergic disease will potentially lead to better endophenotyping, prognostication, prediction of treatment response, and insights into molecular pathways to develop more targeted therapy for these conditions. (J Allergy Clin Immunol 2010;125:S81-94.)	143	93	2010	14	10.1016/j.jaci.2009.10.071	Allergy; Immunology
The roles of the prostaglandin D-2 receptors DP1 and CRTH2 in promoting allergic responses. Prostaglandin D-2 (PGD(2)) is produced by mast cells, Th2 lymphocytes and dendritic cells and has been detected in high concentrations at sites of allergic inflammation. PGD2 exerts its inflammatory effects through high affinity interactions with the G protein coupled receptors DP1 and chemoattractant-homologous receptor expressed on Th2 cells (CRTH2, also known as DP2). DP1 and CRTH2 act in concert to promote a number of biological effects associated with the development and maintenance of the allergic response. During the process of allergen sensitization, DP1 activation may enhance polarization of Th0 cells to Th2 cells by inhibiting production of interleukin 12 by dendritic cells. Upon exposure to allergen in sensitized individuals, activation of DP1 may contribute to the long lasting blood flow changes in the target organ. CRTH2 is expressed by Th2 lymphocytes, eosinophils and basophils and may mediate the recruitment of these cell types during the late phase allergic response. The role played by CRTH2 in promoting the production of Th2 cytokines and IgE make antagonism of this receptor a particularly attractive approach to the treatment of chronic allergic disease.. prostaglandin d-2| dp1| crth2| mast cells| th2 lymphocytes| eosinophils| pi3k| allergic rhinitis| asthma|eosinophilic airway inflammation| d-prostanoid receptor-1| human dendritic cells| helper type-2 cells| chemoattractant receptor| th2 cells| in-vivo| mast-cells| antagonist bay-u-3405| cytokine production.	MAR-2008	prostaglandin d-2| dp1| crth2| mast cells| th2 lymphocytes| eosinophils| pi3k| allergic rhinitis| asthma|eosinophilic airway inflammation| d-prostanoid receptor-1| human dendritic cells| helper type-2 cells| chemoattractant receptor| th2 cells| in-vivo| mast-cells| antagonist bay-u-3405| cytokine production	Pettipher, R	The roles of the prostaglandin D-2 receptors DP1 and CRTH2 in promoting allergic responses		BRITISH JOURNAL OF PHARMACOLOGY	prostaglandin D-2; DP1; CRTH2; mast cells; Th2 lymphocytes; eosinophils; PI3K; allergic rhinitis; asthma	EOSINOPHILIC AIRWAY INFLAMMATION; D-PROSTANOID RECEPTOR-1; HUMAN DENDRITIC CELLS; HELPER TYPE-2 CELLS; CHEMOATTRACTANT RECEPTOR; TH2 CELLS; IN-VIVO; MAST-CELLS; ANTAGONIST BAY-U-3405; CYTOKINE PRODUCTION	Prostaglandin D-2 (PGD(2)) is produced by mast cells, Th2 lymphocytes and dendritic cells and has been detected in high concentrations at sites of allergic inflammation. PGD2 exerts its inflammatory effects through high affinity interactions with the G protein coupled receptors DP1 and chemoattractant-homologous receptor expressed on Th2 cells (CRTH2, also known as DP2). DP1 and CRTH2 act in concert to promote a number of biological effects associated with the development and maintenance of the allergic response. During the process of allergen sensitization, DP1 activation may enhance polarization of Th0 cells to Th2 cells by inhibiting production of interleukin 12 by dendritic cells. Upon exposure to allergen in sensitized individuals, activation of DP1 may contribute to the long lasting blood flow changes in the target organ. CRTH2 is expressed by Th2 lymphocytes, eosinophils and basophils and may mediate the recruitment of these cell types during the late phase allergic response. The role played by CRTH2 in promoting the production of Th2 cytokines and IgE make antagonism of this receptor a particularly attractive approach to the treatment of chronic allergic disease.	93	93	2008	9	10.1038/sj.bjp.0707488	Pharmacology & Pharmacy
Patient understanding, detection, and experience of COPD exacerbations - An observational, interview-based study. Study objectives: This study was conducted to gain insight into patients' comprehension, recognition, and experience of exacerbations of COPD, and to explore the patient burden associated with these events. Design: A qualitative, multinational, cross-sectional, interview-based study. Setting: Patients' homes. Patients: Patients (n = 125) with predominantly moderate-to-very severe COPD (age >= 50 years; with two or more exacerbations during the previous year). Interventions: Patients underwent a 1-h face-to-face interview with a trained interviewer. Measurements and results: During the preceding year, patients experienced a mean +/- SD of 4.6 +/- 5.4 exacerbations, after which 19.2% (n = 24) believed they had not fully recovered. Although commonly used by physicians, only 1.6% (n = 2) of patients understood the term exacerbation, preferring to use simpler terms, such as chest infection (16.0%; n = 20) or crisis (16.0%; n = 20) instead. Approximately two thirds of patients stated that they were aware of when an exacerbation was imminent and, in most cases, patients recounted that symptoms were consistent from one exacerbation to another. Some patients (32.8%; n = 41), however, reported no recognizable warning signs. At the onset of an exacerbation, 32.8% of patients (n = 41) stated that they reacted by self-administering their medication. Some patients spontaneously mentioned a fear of dying (12.0%; n = 15) or suffocating (9.6%; n = 12) during exacerbations, and effects on activities, mood, and personal/family relationships were frequently reported. Physicians tended to underestimate the psychological impact of exacerbations compared with patient reports. Conclusions: This study shows that patients with frequent exacerbations have a poor understanding of the term exacerbation. Patient recollections suggest that exacerbation profiles vary enormously between patients but that symptoms/warning signs are fairly consistent within individuals, and are generally recognizable. Exacerbations appear to have a significant impact on patient well-being, including psychological well-being, and this may be underestimated by physicians.. burden| copd| exacerbation| patient's perspective|obstructive pulmonary-disease| quality-of-life| chronic-bronchitis| health-status| lung-function| time-course| asthma| impact| hospitalization| salmeterol.	JUL-2006	burden| copd| exacerbation| patient's perspective|obstructive pulmonary-disease| quality-of-life| chronic-bronchitis| health-status| lung-function| time-course| asthma| impact| hospitalization| salmeterol	Kessler, R; Stahl, E; Vogelmeier, C; Haughney, J; Trudeau, E; Lofdahl, CG	Patient understanding, detection, and experience of COPD exacerbations - An observational, interview-based study		CHEST	burden; COPD; exacerbation; patient's perspective	OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; CHRONIC-BRONCHITIS; HEALTH-STATUS; LUNG-FUNCTION; TIME-COURSE; ASTHMA; IMPACT; HOSPITALIZATION; SALMETEROL	Study objectives: This study was conducted to gain insight into patients' comprehension, recognition, and experience of exacerbations of COPD, and to explore the patient burden associated with these events. Design: A qualitative, multinational, cross-sectional, interview-based study. Setting: Patients' homes. Patients: Patients (n = 125) with predominantly moderate-to-very severe COPD (age >= 50 years; with two or more exacerbations during the previous year). Interventions: Patients underwent a 1-h face-to-face interview with a trained interviewer. Measurements and results: During the preceding year, patients experienced a mean +/- SD of 4.6 +/- 5.4 exacerbations, after which 19.2% (n = 24) believed they had not fully recovered. Although commonly used by physicians, only 1.6% (n = 2) of patients understood the term exacerbation, preferring to use simpler terms, such as chest infection (16.0%; n = 20) or crisis (16.0%; n = 20) instead. Approximately two thirds of patients stated that they were aware of when an exacerbation was imminent and, in most cases, patients recounted that symptoms were consistent from one exacerbation to another. Some patients (32.8%; n = 41), however, reported no recognizable warning signs. At the onset of an exacerbation, 32.8% of patients (n = 41) stated that they reacted by self-administering their medication. Some patients spontaneously mentioned a fear of dying (12.0%; n = 15) or suffocating (9.6%; n = 12) during exacerbations, and effects on activities, mood, and personal/family relationships were frequently reported. Physicians tended to underestimate the psychological impact of exacerbations compared with patient reports. Conclusions: This study shows that patients with frequent exacerbations have a poor understanding of the term exacerbation. Patient recollections suggest that exacerbation profiles vary enormously between patients but that symptoms/warning signs are fairly consistent within individuals, and are generally recognizable. Exacerbations appear to have a significant impact on patient well-being, including psychological well-being, and this may be underestimated by physicians.	36	93	2006	10	10.1378/chest.130.1.133	General & Internal Medicine; Respiratory System
Endotoxin in inner-city homes: Associations with wheeze and eczema in early childhood. Background: An inverse association between domestic exposure to endotoxin and atopy in childhood has been observed. The relevance of this aspect of the hygiene hypothesis to US inner-city communities that have disproportionately high asthma prevalence has not been determined. Objectives: To measure endotoxin in the dust from inner-city homes, evaluate associations between endotoxin and housing/lifestyle characteristics, and determine whether endotoxin exposure predicted wheeze, allergic rhinitis, and eczema over the first 3 years of life. Methods: As part of an ongoing prospective birth cohort study, children of Dominican and African-American mothers living in New York City underwent repeated questionnaire measures. Dust samples collected from bedroom floors at age 12 or 36 months were assayed for endotoxin. Results: Among the samples collected from 301 participants' homes, the geometric mean endotoxin concentration (95% CI) was 75.9 EU/mg (66-87), and load was 3892 EU/m(2) (3351-4522). Lower endotoxin concentrations were associated with wet mop cleaning and certain neighborhoods. Endotoxin concentration correlated weakly with cockroach (Bla g 2: r = 0.22, P < .001) and mouse (mouse urinary protein: r = 0.28; P < .001) allergens in the dust. Children in homes with higher endotoxin concentration were less likely to have eczema at age 1 year (odds ratio, 0.70 [0.53-0.93]) and more likely to wheeze at age 2 years (odds ratio, 1.34 [1.01-1.78]). These associations were stronger among children with a maternal history of asthma. Conclusion: Endotoxin levels in this inner-city community are similar to those in nonfarm homes elsewhere. In this community, domestic endotoxin exposure was inversely associated with eczema at age 1 year, but positively associated with wheeze at age 2 years. Clinical implications: Endotoxin exposure in the inner-city community may be related to wheeze in the early life; however, given the inverse association seen with eczema, the long-term development of allergic disease is still in question.. endotoxin| asthma| allergy| hygiene hypothesis| wheeze| inner-city| eczema|house-dust endotoxin| hygiene hypothesis| allergic diseases| indoor allergens| national-survey| birth cohort| high-risk| exposure| asthma| children.	MAY-2006	endotoxin| asthma| allergy| hygiene hypothesis| wheeze| inner-city| eczema|house-dust endotoxin| hygiene hypothesis| allergic diseases| indoor allergens| national-survey| birth cohort| high-risk| exposure| asthma| children	Perzanowski, MS; Miller, RL; Thorne, PS; Barr, RG; Divjan, A; Sheares, BJ; Garfinkel, RS; Perera, FP; Goldstein, IF; Chew, GL	Endotoxin in inner-city homes: Associations with wheeze and eczema in early childhood		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	endotoxin; asthma; allergy; hygiene hypothesis; wheeze; inner-city; eczema	HOUSE-DUST ENDOTOXIN; HYGIENE HYPOTHESIS; ALLERGIC DISEASES; INDOOR ALLERGENS; NATIONAL-SURVEY; BIRTH COHORT; HIGH-RISK; EXPOSURE; ASTHMA; CHILDREN	Background: An inverse association between domestic exposure to endotoxin and atopy in childhood has been observed. The relevance of this aspect of the hygiene hypothesis to US inner-city communities that have disproportionately high asthma prevalence has not been determined. Objectives: To measure endotoxin in the dust from inner-city homes, evaluate associations between endotoxin and housing/lifestyle characteristics, and determine whether endotoxin exposure predicted wheeze, allergic rhinitis, and eczema over the first 3 years of life. Methods: As part of an ongoing prospective birth cohort study, children of Dominican and African-American mothers living in New York City underwent repeated questionnaire measures. Dust samples collected from bedroom floors at age 12 or 36 months were assayed for endotoxin. Results: Among the samples collected from 301 participants' homes, the geometric mean endotoxin concentration (95% CI) was 75.9 EU/mg (66-87), and load was 3892 EU/m(2) (3351-4522). Lower endotoxin concentrations were associated with wet mop cleaning and certain neighborhoods. Endotoxin concentration correlated weakly with cockroach (Bla g 2: r = 0.22, P < .001) and mouse (mouse urinary protein: r = 0.28; P < .001) allergens in the dust. Children in homes with higher endotoxin concentration were less likely to have eczema at age 1 year (odds ratio, 0.70 [0.53-0.93]) and more likely to wheeze at age 2 years (odds ratio, 1.34 [1.01-1.78]). These associations were stronger among children with a maternal history of asthma. Conclusion: Endotoxin levels in this inner-city community are similar to those in nonfarm homes elsewhere. In this community, domestic endotoxin exposure was inversely associated with eczema at age 1 year, but positively associated with wheeze at age 2 years. Clinical implications: Endotoxin exposure in the inner-city community may be related to wheeze in the early life; however, given the inverse association seen with eczema, the long-term development of allergic disease is still in question.	39	93	2006	8	10.1016/j.jaci.2005.12.1348	Allergy; Immunology
FT-IR spectroscopy as a tool for rapid identification and intra-species characterization of airborne filamentous fungi. Identification of microfungi is time-consuming due to cultivation and microscopic examination and can be influenced by the interpretation of the macro- and micro-morphological characters observed. Fungal conidia contain mycotoxins that may be present in bioaerosols and thus the capacity for production of mycotoxins (and allergens) needs to be investigated to create a basis for reliable risk assessment in environmental and occupational hygiene. The present investigation aimed to create a simple but sophisticated method for the preparation of samples and the identification of airborne fungi by FT-IR spectroscopy. The method was suited to reproducibly differentiate Aspergillus and Penicillium species on the generic, the species.. and the strain level. There are strong indications that strains of one taxon differing in metabolite production can be reliably distinguished by FT-IR spectroscopy (e.g. Aspergillus parasiticus). On the other hand, species from different taxa being similar in secondary metabolite production showed comparably higher similarities. The results obtained here can serve as a basis for the development of a database for species identification and strain characterization of microfungi. The method presented here will improve and facilitate the risk assessment in case of bioaerosol exposure, as strains with different physiological properties (e.g. toxic, non-toxic) could be differentiated. Moreover, it has the potential to significantly improve the identification of microfungi in various fields of applied microbiological research, e.g. high throughput screening in view of specific physiological properties, biodiversity studies, inventories in environmental microbiology, and quality control measures. (c) 2005 Elsevier B.V. All rights reserved.. ft-ir| fungi| identification| penicillium| aspergillus| conidia| chemotaxonomy|transform-infrared-spectroscopy| performance liquid-chromatography| pyrolysis mass-spectrometry| secondary metabolites| volatile metabolites| typing methods| mycotoxins| strains| differentiation| classification.	JAN-2006	ft-ir| fungi| identification| penicillium| aspergillus| conidia| chemotaxonomy|transform-infrared-spectroscopy| performance liquid-chromatography| pyrolysis mass-spectrometry| secondary metabolites| volatile metabolites| typing methods| mycotoxins| strains| differentiation| classification	Fischer, G; Braun, S; Thissen, R; Dott, W	FT-IR spectroscopy as a tool for rapid identification and intra-species characterization of airborne filamentous fungi		JOURNAL OF MICROBIOLOGICAL METHODS	FT-IR; fungi; identification; Penicillium; Aspergillus; Conidia; chemotaxonomy	TRANSFORM-INFRARED-SPECTROSCOPY; PERFORMANCE LIQUID-CHROMATOGRAPHY; PYROLYSIS MASS-SPECTROMETRY; SECONDARY METABOLITES; VOLATILE METABOLITES; TYPING METHODS; MYCOTOXINS; STRAINS; DIFFERENTIATION; CLASSIFICATION	Identification of microfungi is time-consuming due to cultivation and microscopic examination and can be influenced by the interpretation of the macro- and micro-morphological characters observed. Fungal conidia contain mycotoxins that may be present in bioaerosols and thus the capacity for production of mycotoxins (and allergens) needs to be investigated to create a basis for reliable risk assessment in environmental and occupational hygiene. The present investigation aimed to create a simple but sophisticated method for the preparation of samples and the identification of airborne fungi by FT-IR spectroscopy. The method was suited to reproducibly differentiate Aspergillus and Penicillium species on the generic, the species.. and the strain level. There are strong indications that strains of one taxon differing in metabolite production can be reliably distinguished by FT-IR spectroscopy (e.g. Aspergillus parasiticus). On the other hand, species from different taxa being similar in secondary metabolite production showed comparably higher similarities. The results obtained here can serve as a basis for the development of a database for species identification and strain characterization of microfungi. The method presented here will improve and facilitate the risk assessment in case of bioaerosol exposure, as strains with different physiological properties (e.g. toxic, non-toxic) could be differentiated. Moreover, it has the potential to significantly improve the identification of microfungi in various fields of applied microbiological research, e.g. high throughput screening in view of specific physiological properties, biodiversity studies, inventories in environmental microbiology, and quality control measures. (c) 2005 Elsevier B.V. All rights reserved.	48	93	2006	15	10.1016/j.mimet.2005.04.005	Biochemistry & Molecular Biology; Microbiology
Selected oxidized fragrance terpenes are common contact allergens. Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air-exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3% showed a positive reaction to oxidized linalool and 1.1% to the hydroperoxide fraction. About 0.5% of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58% had fragrance-related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.. allergic contact dermatitis| autoxidation| caryophyllene| fragrance allergy| fragrance mix| hydroperoxides| linalool| myrcene| oxidation products| patch testing|airborne compositae dermatitis| d-limonene| hand eczema| colophony| oil| sensitization| linalool| hydroperoxide| monoterpenes| turpentine.	JUN-2005	allergic contact dermatitis| autoxidation| caryophyllene| fragrance allergy| fragrance mix| hydroperoxides| linalool| myrcene| oxidation products| patch testing|airborne compositae dermatitis| d-limonene| hand eczema| colophony| oil| sensitization| linalool| hydroperoxide| monoterpenes| turpentine	Matura, M; Skold, M; Borje, A; Andersen, KE; Bruze, M; Frosch, P; Goossens, A; Johansen, JD; Svedman, C; White, IR; Karlberg, AT	Selected oxidized fragrance terpenes are common contact allergens		CONTACT DERMATITIS	allergic contact dermatitis; autoxidation; caryophyllene; fragrance allergy; fragrance mix; hydroperoxides; linalool; myrcene; oxidation products; patch testing	AIRBORNE COMPOSITAE DERMATITIS; D-LIMONENE; HAND ECZEMA; COLOPHONY; OIL; SENSITIZATION; LINALOOL; HYDROPEROXIDE; MONOTERPENES; TURPENTINE	Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air-exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3% showed a positive reaction to oxidized linalool and 1.1% to the hydroperoxide fraction. About 0.5% of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58% had fragrance-related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.	45	93	2005	9	10.1111/j.0105-1873.2005.00605.x	Allergy; Dermatology
Allergen exposure in infancy and the development of sensitization, wheeze, and asthma at 4 years. Background: The relationship between mite and pet allergen exposure in infancy and the subsequent development of sensitization and asthma is complex. Objective: We prospectively investigated the effect of allergen exposure at 3 months of age on the development of sensitization, wheeze, and physician-diagnosed asthma in the first 4 years of life in a birth cohort of children with and without an atopic mother. Methods: Children participated in the Prevention and Incidence of Asthma and Mite Allergy study. Allergen exposure at 3 months of age was determined from mattress dust samples. Specific IgE to inhalant allergens was measured at 4 years of age, and information about wheeze and physician-diagnosed asthma was collected with yearly questionnaires. Results: Mite and cat allergen exposure in infancy were associated with an increased risk of specific sensitization to house dust mite and cat, respectively, at 4 years of age. There were borderline significant associations between cat allergen exposure and persistent wheeze in the total study population and between dog allergen exposure and persistent wheeze in children with a nonatopic mother. In children with an atopic mother, there was some indication of a positive association between mite allergen exposure and physician-diagnosed asthma. Conclusion: Early house dust mite and cat allergen exposure might lead to sensitization and, in case of cat allergen exposure, to persistent wheeze. Early mite and dog allergen exposure might lead to asthma and persistent wheeze, respectively, but only in subgroups defined by maternal atopy.. cohort studies| child| preschool| allergens| house dust mites| cats| dogs| sensitization| wheezing| asthma|house-dust mite| birth cohort| maternal history| indoor allergens| risk-factor| 1st year| life| childhood| atopy| pet.	MAY-2005	cohort studies| child| preschool| allergens| house dust mites| cats| dogs| sensitization| wheezing| asthma|house-dust mite| birth cohort| maternal history| indoor allergens| risk-factor| 1st year| life| childhood| atopy| pet	Brussee, JE; Smit, HA; van Strien, RT; Corver, K; Kerkhof, M; Wijga, AH; Aalberse, RC; Postma, D; Gerritsen, J; Grobbee, DE; de Jongste, JC; Brunekreef, B	Allergen exposure in infancy and the development of sensitization, wheeze, and asthma at 4 years		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	cohort studies; child; preschool; allergens; house dust mites; cats; dogs; sensitization; wheezing; asthma	HOUSE-DUST MITE; BIRTH COHORT; MATERNAL HISTORY; INDOOR ALLERGENS; RISK-FACTOR; 1ST YEAR; LIFE; CHILDHOOD; ATOPY; PET	Background: The relationship between mite and pet allergen exposure in infancy and the subsequent development of sensitization and asthma is complex. Objective: We prospectively investigated the effect of allergen exposure at 3 months of age on the development of sensitization, wheeze, and physician-diagnosed asthma in the first 4 years of life in a birth cohort of children with and without an atopic mother. Methods: Children participated in the Prevention and Incidence of Asthma and Mite Allergy study. Allergen exposure at 3 months of age was determined from mattress dust samples. Specific IgE to inhalant allergens was measured at 4 years of age, and information about wheeze and physician-diagnosed asthma was collected with yearly questionnaires. Results: Mite and cat allergen exposure in infancy were associated with an increased risk of specific sensitization to house dust mite and cat, respectively, at 4 years of age. There were borderline significant associations between cat allergen exposure and persistent wheeze in the total study population and between dog allergen exposure and persistent wheeze in children with a nonatopic mother. In children with an atopic mother, there was some indication of a positive association between mite allergen exposure and physician-diagnosed asthma. Conclusion: Early house dust mite and cat allergen exposure might lead to sensitization and, in case of cat allergen exposure, to persistent wheeze. Early mite and dog allergen exposure might lead to asthma and persistent wheeze, respectively, but only in subgroups defined by maternal atopy.	29	93	2005	7	10.1016/j.jaci.2005.02.035	Allergy; Immunology
Toll-like receptor 4 or 2 agonists decrease allergic inflammation. Toll-like receptors (TLRs) recognize highly conserved microbial molecular patterns, such as found in endotoxin. This study tested whether TLR4 and TLR2 stimulation in vivo would modulate subsequent adaptive (allergic) immune responses. We analyzed the effects of pulmonary administration of a TLR4 agonist, lipid A (LpA), and two TLR2 agonists, peptidoglycan (Ppg) and PamCys, in a murine model of allergic inflammation. The TLR agonists were administered during allergen sensitization or challenge. Both TLR agonists decreased the allergen-induced pulmonary recruitment of eosinophils when administered at sensitization or challenge. When given before sensitization, the TLR4 and TLR2 agonists decreased additional allergen-induced parameters of inflammation (pulmonary eosinophilia, bronchoalveolar lavage IL-13, total serum IgE, and airway hyperresponsiveness). Interestingly, TLR4 and TLR2 agonists decreased the number of CD4+ cells in the lung. Also, at the site of local allergen stimulation, the draining thoracic lymph nodes, allergen-induced lymphocyte proliferation, and IL-13 secretion were decreased by administration of LpA and Ppg. These data provide a distinct example of the modulation of adaptive (allergic) responses by non-antigen-dependent stimuli. Our findings also demonstrate that both TLR4 and TLR2 agonists decrease allergic responses, supporting the concept that exposure to bacterial components under defined conditions may protect against allergic disease.. innate| immunity| asthma| toll-like receptor 4| toll-like receptor 2| allergy|airway hyperresponsiveness| pulmonary inflammation| immune-responses| murine model| bacterial lipopolysaccharide| dendritic cells| th2 responses| t-cells| asthma| endotoxin.	MAR-2005	innate| immunity| asthma| toll-like receptor 4| toll-like receptor 2| allergy|airway hyperresponsiveness| pulmonary inflammation| immune-responses| murine model| bacterial lipopolysaccharide| dendritic cells| th2 responses| t-cells| asthma| endotoxin	Velasco, G; Campo, M; Manrique, OJ; Bellou, A; He, HZ; Arestides, RSS; Schaub, B; Perkins, DL; Finn, PW	Toll-like receptor 4 or 2 agonists decrease allergic inflammation		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	innate; immunity; asthma; Toll-like receptor 4; Toll-like receptor 2; allergy	AIRWAY HYPERRESPONSIVENESS; PULMONARY INFLAMMATION; IMMUNE-RESPONSES; MURINE MODEL; BACTERIAL LIPOPOLYSACCHARIDE; DENDRITIC CELLS; TH2 RESPONSES; T-CELLS; ASTHMA; ENDOTOXIN	Toll-like receptors (TLRs) recognize highly conserved microbial molecular patterns, such as found in endotoxin. This study tested whether TLR4 and TLR2 stimulation in vivo would modulate subsequent adaptive (allergic) immune responses. We analyzed the effects of pulmonary administration of a TLR4 agonist, lipid A (LpA), and two TLR2 agonists, peptidoglycan (Ppg) and PamCys, in a murine model of allergic inflammation. The TLR agonists were administered during allergen sensitization or challenge. Both TLR agonists decreased the allergen-induced pulmonary recruitment of eosinophils when administered at sensitization or challenge. When given before sensitization, the TLR4 and TLR2 agonists decreased additional allergen-induced parameters of inflammation (pulmonary eosinophilia, bronchoalveolar lavage IL-13, total serum IgE, and airway hyperresponsiveness). Interestingly, TLR4 and TLR2 agonists decreased the number of CD4+ cells in the lung. Also, at the site of local allergen stimulation, the draining thoracic lymph nodes, allergen-induced lymphocyte proliferation, and IL-13 secretion were decreased by administration of LpA and Ppg. These data provide a distinct example of the modulation of adaptive (allergic) responses by non-antigen-dependent stimuli. Our findings also demonstrate that both TLR4 and TLR2 agonists decrease allergic responses, supporting the concept that exposure to bacterial components under defined conditions may protect against allergic disease.	38	93	2005	7	10.1165/rcmb.2003-0435OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: Results from the National Survey of Lead and Allergens in Housing. Background: Exposures to dog and cat allergens are believed to play important roles in the etiology of asthma; however, the levels of these allergens have never been assessed in a representative sample of US homes. Objective: The objective of this study was to estimate and characterize exposures to Can f 1 (dog allergen) and Fell d 1 (cat allergen) in US homes. Methods: Data were obtained from the National Survey of Lead and Allergens in Housing, a nationally representative survey of 831 US homes. Vacuumed-collected dust samples from the bed, bedroom floor, living room floor, and living room sofa were analyzed for concentrations of Can f 1 and Fel d 1 (micrograms of allergen per gram of dust). Results: Although a dog or cat had lived in only 49.1% of homes in the previous 6 months, Can f 1 and Fel d 1 were detected in 100% and 99.9% of homes, respectively. Averaged over the sampled sites, geometric mean concentrations (mug/g) were 4.69 for Can f 1 and 4.73 for Fel d 1. Among homes with an indoor dog and cat, respectively, geometric mean concentrations were 69 for Can f 1 and 200 for Fel d 1. Among homes without the indoor pet, geometric mean concentrations were above 1.0. The independent predictors of elevated concentrations in homes without pets were all demographic variables that were also linked to a higher prevalence of pet ownership. Conclusions: Can f 1 and Fel d 1 are universally present in US homes. Levels that have been associated with an increased risk of allergic sensitization were found even in homes without pets. Because of the transportability of these allergens on clothing, elevated levels in homes without pets, particularly among demographic groups in which pet ownership is more prevalent, implicate the community as an important source of these pet allergens.. allergens| asthma| cat allergen| can f 1| dog allergen| epidemiology| fel d 1| survey|dust mite| d-i| cockroach allergens| domestic allergens| public places| particle-size| risk-factors| los-alamos| new-mexico| f i.	JUL-2004	allergens| asthma| cat allergen| can f 1| dog allergen| epidemiology| fel d 1| survey|dust mite| d-i| cockroach allergens| domestic allergens| public places| particle-size| risk-factors| los-alamos| new-mexico| f i	Arbes, SJ; Cohn, RD; Yin, M; Muilenberg, ML; Friedman, W; Zeldin, DC	Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: Results from the National Survey of Lead and Allergens in Housing		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergens; asthma; cat allergen; Can f 1; dog allergen; epidemiology; Fel d 1; survey	DUST MITE; D-I; COCKROACH ALLERGENS; DOMESTIC ALLERGENS; PUBLIC PLACES; PARTICLE-SIZE; RISK-FACTORS; LOS-ALAMOS; NEW-MEXICO; F I	Background: Exposures to dog and cat allergens are believed to play important roles in the etiology of asthma; however, the levels of these allergens have never been assessed in a representative sample of US homes. Objective: The objective of this study was to estimate and characterize exposures to Can f 1 (dog allergen) and Fell d 1 (cat allergen) in US homes. Methods: Data were obtained from the National Survey of Lead and Allergens in Housing, a nationally representative survey of 831 US homes. Vacuumed-collected dust samples from the bed, bedroom floor, living room floor, and living room sofa were analyzed for concentrations of Can f 1 and Fel d 1 (micrograms of allergen per gram of dust). Results: Although a dog or cat had lived in only 49.1% of homes in the previous 6 months, Can f 1 and Fel d 1 were detected in 100% and 99.9% of homes, respectively. Averaged over the sampled sites, geometric mean concentrations (mug/g) were 4.69 for Can f 1 and 4.73 for Fel d 1. Among homes with an indoor dog and cat, respectively, geometric mean concentrations were 69 for Can f 1 and 200 for Fel d 1. Among homes without the indoor pet, geometric mean concentrations were above 1.0. The independent predictors of elevated concentrations in homes without pets were all demographic variables that were also linked to a higher prevalence of pet ownership. Conclusions: Can f 1 and Fel d 1 are universally present in US homes. Levels that have been associated with an increased risk of allergic sensitization were found even in homes without pets. Because of the transportability of these allergens on clothing, elevated levels in homes without pets, particularly among demographic groups in which pet ownership is more prevalent, implicate the community as an important source of these pet allergens.	32	93	2004	7	10.1016/j.jaci.2004.04.036	Allergy; Immunology
Parental smoking in childhood and adult obstructive lung disease: results from the European Community Respiratory Health Survey. Background: Early exposure to parental smoking appears to influence the development of the airways and predispose to respiratory symptoms. A study was undertaken to determine whether the consequences of parental smoking could be traced in adulthood. Methods: Information from interviewer-led questionnaires was available for 18922 subjects aged 20-44 years from random population samples in 37 areas participating in the European Community Respiratory Health Survey. Lung function data were available for 15-901 subjects. Results: In men, father's smoking in childhood was associated with more respiratory symptoms (ORwheeze 1.13 (95% CI 1.00 to 1.28); never smokers: ORwheeze 1.21 (95% CI 0.96 to 1.50)) and there was a dose-dependent association between number of parents smoking and wheeze (one: OR 1.08 (95% CI 0.94 to 1.24); both: OR 1.24 (95% CI 1.05 to 1.47); p(trend)=0.010). A reduced ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) was related to father's smoking (-0.3% (95% CI -0.6 to 0)) and number of parents smoking (p(trend)<0.001) among men. In women, mother's smoking was associated with more respiratory symptoms and poorer lung function (ORwheeze 1.15 (95% CI 1.01 to 1.31), never smokers: ORwheeze 1.21 (95% CI 0.98-1.51); FEV1-24 ml (95% CI -45 to -3); FEV1/FVC ratio -0.6% (95% CI -0.9 to -0.3)). These effects were possibly accounted for by maternal smoking in pregnancy (ORwheeze 1.39 (95% CI 1.17 to 1.65); FEV1-23 ml (95% CI -52 to 7); FEV1/FVC ratio -0.9% (95% CI -1.3 to -0.4)) as there was no association with paternal smoking among women (interaction by sex, p<0.05). These results were homogeneous across centres. Conclusion: Both intrauterine and environmental exposure to parental tobacco smoking was related to more respiratory symptoms and poorer lung function in adulthood in this multicultural study. The age window of particular vulnerability appeared to differ by sex, postnatal exposure being important only in men and a role for prenatal exposure being more evident in women.. maternal smoking| tobacco-smoke| cigarette-smoking| young-adults| asthma| exposure| life| prevalence| pregnancy| population.	APR 1-2004	maternal smoking| tobacco-smoke| cigarette-smoking| young-adults| asthma| exposure| life| prevalence| pregnancy| population	Svanes, C; Omenaas, E; Jarvis, D; Chinn, S; Gulsvik, A; Burney, P	Parental smoking in childhood and adult obstructive lung disease: results from the European Community Respiratory Health Survey		THORAX		MATERNAL SMOKING; TOBACCO-SMOKE; CIGARETTE-SMOKING; YOUNG-ADULTS; ASTHMA; EXPOSURE; LIFE; PREVALENCE; PREGNANCY; POPULATION	Background: Early exposure to parental smoking appears to influence the development of the airways and predispose to respiratory symptoms. A study was undertaken to determine whether the consequences of parental smoking could be traced in adulthood. Methods: Information from interviewer-led questionnaires was available for 18922 subjects aged 20-44 years from random population samples in 37 areas participating in the European Community Respiratory Health Survey. Lung function data were available for 15-901 subjects. Results: In men, father's smoking in childhood was associated with more respiratory symptoms (ORwheeze 1.13 (95% CI 1.00 to 1.28); never smokers: ORwheeze 1.21 (95% CI 0.96 to 1.50)) and there was a dose-dependent association between number of parents smoking and wheeze (one: OR 1.08 (95% CI 0.94 to 1.24); both: OR 1.24 (95% CI 1.05 to 1.47); p(trend)=0.010). A reduced ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) was related to father's smoking (-0.3% (95% CI -0.6 to 0)) and number of parents smoking (p(trend)<0.001) among men. In women, mother's smoking was associated with more respiratory symptoms and poorer lung function (ORwheeze 1.15 (95% CI 1.01 to 1.31), never smokers: ORwheeze 1.21 (95% CI 0.98-1.51); FEV1-24 ml (95% CI -45 to -3); FEV1/FVC ratio -0.6% (95% CI -0.9 to -0.3)). These effects were possibly accounted for by maternal smoking in pregnancy (ORwheeze 1.39 (95% CI 1.17 to 1.65); FEV1-23 ml (95% CI -52 to 7); FEV1/FVC ratio -0.9% (95% CI -1.3 to -0.4)) as there was no association with paternal smoking among women (interaction by sex, p<0.05). These results were homogeneous across centres. Conclusion: Both intrauterine and environmental exposure to parental tobacco smoking was related to more respiratory symptoms and poorer lung function in adulthood in this multicultural study. The age window of particular vulnerability appeared to differ by sex, postnatal exposure being important only in men and a role for prenatal exposure being more evident in women.	30	93	2004	8	10.1136/thx.2003.009746	Respiratory System
Influence of outdoor aeroallergens on hospitalization for asthma in Canada. Background: The risk of hospitalization for asthma caused by outdoor aeroallergens is largely unknown. Objective: The objective of this study was to determine the association between changes in outdoor aeroallergens and hospitalizations for asthma from the Pacific coast to the Atlantic coast of Canada. Methods: A daily time series analysis was done to test the association between daily changes in aeroallergens and daily changes in hospitalizations for asthma during a 7-year period between 1993 and 2000 in 10 of the largest cities in Canada. Results were adjusted for long-term trends, day of the week, climate, and air pollution. Results: A daily increase, equivalent to the mean value of each allergen, was associated with the following percentage increase in asthma hospitalizations: 3.3% (95% CI, 2.3 to 4.1) for basidiomycetes, 3.1 % (95 % CI, 2.8 to 5.7) for ascomycetes, 3.2% (95% CI, 1.6 to 4.8) for deuteromycetes, 3.0% (95% CI, 1.1 to 4.9) for weeds, 2.9 % (95 % CI, 0.9 to 5.0) for trees, and 2.0% (95% CI, 1.1 to 2.8) for grasses. After accounting for the independent effects of trees and ozone, the combination of the 2 was associated with an additional 0.22% increase in admissions averaged across cities (P < .05). Conclusion: These findings provide evidence for the hypothesis that aeroallergens are an important cause of severe asthma morbidity across Canada,, and in some situations there might be a modest synergistic adverse effect of ozone and aeroallergens combined.. asthma| fungus| pollen| air pollution| epidemiology|inhaled allergen| airway response| ozone exposure| pollen.	FEB-2004	asthma| fungus| pollen| air pollution| epidemiology|inhaled allergen| airway response| ozone exposure| pollen	Dales, RE; Cakmak, S; Judek, S; Dann, T; Coates, F; Brook, JR; Burnett, RT	Influence of outdoor aeroallergens on hospitalization for asthma in Canada		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; fungus; pollen; air pollution; epidemiology	INHALED ALLERGEN; AIRWAY RESPONSE; OZONE EXPOSURE; POLLEN	Background: The risk of hospitalization for asthma caused by outdoor aeroallergens is largely unknown. Objective: The objective of this study was to determine the association between changes in outdoor aeroallergens and hospitalizations for asthma from the Pacific coast to the Atlantic coast of Canada. Methods: A daily time series analysis was done to test the association between daily changes in aeroallergens and daily changes in hospitalizations for asthma during a 7-year period between 1993 and 2000 in 10 of the largest cities in Canada. Results were adjusted for long-term trends, day of the week, climate, and air pollution. Results: A daily increase, equivalent to the mean value of each allergen, was associated with the following percentage increase in asthma hospitalizations: 3.3% (95% CI, 2.3 to 4.1) for basidiomycetes, 3.1 % (95 % CI, 2.8 to 5.7) for ascomycetes, 3.2% (95% CI, 1.6 to 4.8) for deuteromycetes, 3.0% (95% CI, 1.1 to 4.9) for weeds, 2.9 % (95 % CI, 0.9 to 5.0) for trees, and 2.0% (95% CI, 1.1 to 2.8) for grasses. After accounting for the independent effects of trees and ozone, the combination of the 2 was associated with an additional 0.22% increase in admissions averaged across cities (P < .05). Conclusion: These findings provide evidence for the hypothesis that aeroallergens are an important cause of severe asthma morbidity across Canada,, and in some situations there might be a modest synergistic adverse effect of ozone and aeroallergens combined.	23	93	2004	4	10.1016/j.jaci.2003.11.016	Allergy; Immunology
Natural killer and dendritic cell contact in lesional atopic dermatitis skin - Malassezia-influenced cell interaction. The regulation of dendritic cells is far from fully understood. Interestingly, several recent reports have suggested a role for natural killer cells in affecting dendritic cell maturation and function upon direct contact between the cells. It is not known if this interaction takes place also in vivo, or if a potential interaction of natural killer cells and dendritic cells would be affected by allergen exposure of the dendritic cells. The yeast Malassezia can act as an allergen in atopic eczema/dermatitis syndrome, and induce maturation of dendritic cells. Our aims were to study the distribution of natural killer cells in the skin from atopic eczema/dermatitis syndrome patients with the emphasis on possible natural killer cell-dendritic cell interaction, and to assess whether the interaction of Malassezia with dendritic cells would affect subsequent interaction between dendritic cells and natural killer cells. A few scattered natural killer (CD56(+)/CD3(-)) cells were found in the dermis of healthy individuals and in nonlesional skin from atopic eczema/dermatitis syndrome patients. In lesional skin and in biopsies from Malassezia atopy-patch-test-positive skin, however, natural killer cells were differentially distributed and for the first time we could show close contact between natural killer cells and CD1a(+) dendritic cells. Dendritic cells preincubated with Malassezia became less susceptible to natural-killer-cell-induced cell death, suggesting a direct effect imposed by Malassezia upon interaction of dendritic cells with natural killer cells. These findings indicate that natural killer cells and dendritic cells can interact in the skin and that Malassezia affects the interaction between natural killer cells and dendritic cells. Our data suggest that natural killer cells may play a role in regulating dendritic cells in atopic eczema/dermatitis syndrome.. cell communication| cell death| eczema|nk cells| pityrosporum orbiculare| mediated lysis| human blood| in-vivo| expression| receptors| subsets| furfur| maturation.	OCT-2002	cell communication| cell death| eczema|nk cells| pityrosporum orbiculare| mediated lysis| human blood| in-vivo| expression| receptors| subsets| furfur| maturation	Buentke, E; Heffler, LC; Wilson, JL; Wallin, RPA; Lofman, C; Chambers, BJ; Ljunggren, HG; Scheynius, A	Natural killer and dendritic cell contact in lesional atopic dermatitis skin - Malassezia-influenced cell interaction		JOURNAL OF INVESTIGATIVE DERMATOLOGY	cell communication; cell death; eczema	NK CELLS; PITYROSPORUM ORBICULARE; MEDIATED LYSIS; HUMAN BLOOD; IN-VIVO; EXPRESSION; RECEPTORS; SUBSETS; FURFUR; MATURATION	The regulation of dendritic cells is far from fully understood. Interestingly, several recent reports have suggested a role for natural killer cells in affecting dendritic cell maturation and function upon direct contact between the cells. It is not known if this interaction takes place also in vivo, or if a potential interaction of natural killer cells and dendritic cells would be affected by allergen exposure of the dendritic cells. The yeast Malassezia can act as an allergen in atopic eczema/dermatitis syndrome, and induce maturation of dendritic cells. Our aims were to study the distribution of natural killer cells in the skin from atopic eczema/dermatitis syndrome patients with the emphasis on possible natural killer cell-dendritic cell interaction, and to assess whether the interaction of Malassezia with dendritic cells would affect subsequent interaction between dendritic cells and natural killer cells. A few scattered natural killer (CD56(+)/CD3(-)) cells were found in the dermis of healthy individuals and in nonlesional skin from atopic eczema/dermatitis syndrome patients. In lesional skin and in biopsies from Malassezia atopy-patch-test-positive skin, however, natural killer cells were differentially distributed and for the first time we could show close contact between natural killer cells and CD1a(+) dendritic cells. Dendritic cells preincubated with Malassezia became less susceptible to natural-killer-cell-induced cell death, suggesting a direct effect imposed by Malassezia upon interaction of dendritic cells with natural killer cells. These findings indicate that natural killer cells and dendritic cells can interact in the skin and that Malassezia affects the interaction between natural killer cells and dendritic cells. Our data suggest that natural killer cells may play a role in regulating dendritic cells in atopic eczema/dermatitis syndrome.	46	93	2002	8	10.1046/j.1523-1747.2002.00132.x	Dermatology
Association of body mass index with respiratory symptoms and atopy: results from the European Community Respiratory Health Survey. Background There are several reports showing that obese adults report more respiratory symptoms suggestive of asthma than those who are not obese. Objective To determine the association of body mass index with respiratory symptoms and atopy in young adults Method Information collected from 15 454 participants in the European Community Respiratory Health Survey, a multicentre cross-sectional survey of young adults, was analysed to determine the association of body mass index with respiratory symptoms and atopy. Results Men and women with a body mass index of greater than 30 were at an increased risk of wheeze with shortness of breath compared with those with a body mass of 20-24.99 (OR in men 1.85, 95% confidence interval 1.41-2.42; OR in women 2.03, 95% confidence interval 1.59-2.58). Similar associations were observed for other symptoms suggestive or asthma, Body mass index was not associated with 'hayfever or nasal allergies', specific IgE to house dust mite. grass or cat or with total IgE in men or women. Conclusion Reported associations of body mass index with symptoms suggestive of asthma are unlikely to be explained by a higher risk of atopy in the obese. Alternative explanations must be sought.. young-adults| asthma| obesity| weight| overweight| children| wheeze| leptin| risk.	JUN-2002	young-adults| asthma| obesity| weight| overweight| children| wheeze| leptin| risk	Jarvis, D; Chinn, S; Potts, J; Burney, P	Association of body mass index with respiratory symptoms and atopy: results from the European Community Respiratory Health Survey		CLINICAL AND EXPERIMENTAL ALLERGY		YOUNG-ADULTS; ASTHMA; OBESITY; WEIGHT; OVERWEIGHT; CHILDREN; WHEEZE; LEPTIN; RISK	Background There are several reports showing that obese adults report more respiratory symptoms suggestive of asthma than those who are not obese. Objective To determine the association of body mass index with respiratory symptoms and atopy in young adults Method Information collected from 15 454 participants in the European Community Respiratory Health Survey, a multicentre cross-sectional survey of young adults, was analysed to determine the association of body mass index with respiratory symptoms and atopy. Results Men and women with a body mass index of greater than 30 were at an increased risk of wheeze with shortness of breath compared with those with a body mass of 20-24.99 (OR in men 1.85, 95% confidence interval 1.41-2.42; OR in women 2.03, 95% confidence interval 1.59-2.58). Similar associations were observed for other symptoms suggestive or asthma, Body mass index was not associated with 'hayfever or nasal allergies', specific IgE to house dust mite. grass or cat or with total IgE in men or women. Conclusion Reported associations of body mass index with symptoms suggestive of asthma are unlikely to be explained by a higher risk of atopy in the obese. Alternative explanations must be sought.	26	93	2002	7	10.1046/j.1365-2222.2002.01380.x	Allergy; Immunology
Deteriorated housing contributes to high cockroach allergen levels in inner-city households. The high prevalence of childhood asthma in low-income, inner-city populations is not fully understood but has been at least partly attributed to the disproportionate exposures associated with socioeconomic disadvantage. The contribution of indoor allergens to asthma is well documented, but links between socioeconomic disadvantage and indoor allergen levels are not clear. We investigated levels of cockroach allergens (Bla g 2) in a sample of 132 Dominican or African American low-income households with young children in northern Manhattan in New York City (40% were receiving public assistance) to determine whether the distribution of allergens is a function of housing deterioration. Deterioration was measured by the presence and number of physical housing problems (holes in the ceilings and walls, water damage, etc.). More than 50% of the sample had two or more types of housing dilapidation, and 67% of the sample reported cockroach sightings in their homes. Samples of dust were collected from kitchen and bedroom surfaces. We hypothesized that the greater the dilapidation, the higher the allergen levels, independent of income, sociocultural factors, and pest-control methods. In addition, we hypothesized that the homes of families characterized by frequent moves (23.5%) would have higher allergen levels than more stable families. Results showed significant positive associations between housing deterioration and allergen levels in kitchens, after adjusting for income and ethnicity, with independent effects of residential stability (p < 0.05). Bedroom allergen levels were associated with housing instability (p < 0.01) and etlinicity (p < 0.01). Findings demonstrated that indoor household allergen levels are related to degree of household disrepair, after adjusting for individual family attributes, suggesting that social-structural aspects of housing may be appropriate targets for public health interventions designed to reduce allergen exposure.. childhood asthma| cockroach allergens| housing problems| inner-city minority populations|indoor allergens| socioeconomic-status| risk-factors| black-women| asthma| exposure| children| childhood| health| sensitization.	APR-2002	childhood asthma| cockroach allergens| housing problems| inner-city minority populations|indoor allergens| socioeconomic-status| risk-factors| black-women| asthma| exposure| children| childhood| health| sensitization	Rauh, VA; Chew, GL; Garfinkel, RS	Deteriorated housing contributes to high cockroach allergen levels in inner-city households		ENVIRONMENTAL HEALTH PERSPECTIVES	childhood asthma; cockroach allergens; housing problems; inner-city minority populations	INDOOR ALLERGENS; SOCIOECONOMIC-STATUS; RISK-FACTORS; BLACK-WOMEN; ASTHMA; EXPOSURE; CHILDREN; CHILDHOOD; HEALTH; SENSITIZATION	The high prevalence of childhood asthma in low-income, inner-city populations is not fully understood but has been at least partly attributed to the disproportionate exposures associated with socioeconomic disadvantage. The contribution of indoor allergens to asthma is well documented, but links between socioeconomic disadvantage and indoor allergen levels are not clear. We investigated levels of cockroach allergens (Bla g 2) in a sample of 132 Dominican or African American low-income households with young children in northern Manhattan in New York City (40% were receiving public assistance) to determine whether the distribution of allergens is a function of housing deterioration. Deterioration was measured by the presence and number of physical housing problems (holes in the ceilings and walls, water damage, etc.). More than 50% of the sample had two or more types of housing dilapidation, and 67% of the sample reported cockroach sightings in their homes. Samples of dust were collected from kitchen and bedroom surfaces. We hypothesized that the greater the dilapidation, the higher the allergen levels, independent of income, sociocultural factors, and pest-control methods. In addition, we hypothesized that the homes of families characterized by frequent moves (23.5%) would have higher allergen levels than more stable families. Results showed significant positive associations between housing deterioration and allergen levels in kitchens, after adjusting for income and ethnicity, with independent effects of residential stability (p < 0.05). Bedroom allergen levels were associated with housing instability (p < 0.01) and etlinicity (p < 0.01). Findings demonstrated that indoor household allergen levels are related to degree of household disrepair, after adjusting for individual family attributes, suggesting that social-structural aspects of housing may be appropriate targets for public health interventions designed to reduce allergen exposure.	39	93	2002	5		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Remodeling of the airway epithelium in asthma. Several pathologic changes occur in the airway epithelium in asthma, but the relationship between these changes and the initiation and progression of asthma remains poorly understood. One possibility is that changes in the structure and function of the epithelium induced by environmental exposure in genetically susceptible subjects represent primary pivotal events that occur early in the pathogenesis of asthma. Alternatively, these epithelial changes may occur simply as a consequence of pivotal early events in other systems, such as immune deviation in childhood to a helper T cell type 2 (Th2) subtype of CD4* cells. Epithelial desquamation in asthma represents a pathologic change that is frequently cited as important for the mechanisms of airway remodeling and airway hyperresponsiveness. Desquamation of the epithelium may not represent true pathology, however, but may instead be an artifact of tissue sampling and handling. Evidence is more firm for other pathologic changes in the epithelium. For example, goblet cell numbers are increased in asthma, leading to increases in stored mucins in the epithelium and in secreted mucins in sputum. The functional consequences of these changes include sputum production and airway narrowing, which lead to asthma exacerbations. Currently available data suggest that an important mechanism for goblet cell hyperplasia in asthma is the action of Th2 cytokines. Improved understanding of epithelial goblet cell abnormalities in asthma will hopefully lead to novel therapies for mucin hypersecretion, which is an important cause of morbidity and mortality.. asthma| desquamation| epithelium| goblet cell| mucin|goblet cell metaplasia| bronchoalveolar lavage fluid| gland serous cells| mild asthma| bronchial epithelium| mucus production| induced sputum| plasma exudation| murine model| inflammation.	NOV 15-2001	asthma| desquamation| epithelium| goblet cell| mucin|goblet cell metaplasia| bronchoalveolar lavage fluid| gland serous cells| mild asthma| bronchial epithelium| mucus production| induced sputum| plasma exudation| murine model| inflammation	Fahy, JV	Remodeling of the airway epithelium in asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; desquamation; epithelium; goblet cell; mucin	GOBLET CELL METAPLASIA; BRONCHOALVEOLAR LAVAGE FLUID; GLAND SEROUS CELLS; MILD ASTHMA; BRONCHIAL EPITHELIUM; MUCUS PRODUCTION; INDUCED SPUTUM; PLASMA EXUDATION; MURINE MODEL; INFLAMMATION	Several pathologic changes occur in the airway epithelium in asthma, but the relationship between these changes and the initiation and progression of asthma remains poorly understood. One possibility is that changes in the structure and function of the epithelium induced by environmental exposure in genetically susceptible subjects represent primary pivotal events that occur early in the pathogenesis of asthma. Alternatively, these epithelial changes may occur simply as a consequence of pivotal early events in other systems, such as immune deviation in childhood to a helper T cell type 2 (Th2) subtype of CD4* cells. Epithelial desquamation in asthma represents a pathologic change that is frequently cited as important for the mechanisms of airway remodeling and airway hyperresponsiveness. Desquamation of the epithelium may not represent true pathology, however, but may instead be an artifact of tissue sampling and handling. Evidence is more firm for other pathologic changes in the epithelium. For example, goblet cell numbers are increased in asthma, leading to increases in stored mucins in the epithelium and in secreted mucins in sputum. The functional consequences of these changes include sputum production and airway narrowing, which lead to asthma exacerbations. Currently available data suggest that an important mechanism for goblet cell hyperplasia in asthma is the action of Th2 cytokines. Improved understanding of epithelial goblet cell abnormalities in asthma will hopefully lead to novel therapies for mucin hypersecretion, which is an important cause of morbidity and mortality.	75	93	2001	6		General & Internal Medicine; Respiratory System
Persistent airflow limitation in adult-onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniae infection. Background: Persistent airflow limitation may develop in patients with asthma, particularly in adults with nonatopic (intrinsic) disease. Although the underlying mechanisms are still unknown, respiratory infections might be involved. Objective: We investigated the annual loss of lung function in relation to seropositivity to Chlamydia pneumoniae in different subgroups of patients with severe asthma according to age at onset of asthma and atopic status. Methods: One hundred one nonsmoking outpatients with a pulmonologist's diagnosis of severe asthma (32 men and 69 women; mean age, 46.0 years; range, 18-75 years) were included in a cross-sectional study. C pneumoniae-specific serum IgG and IgA were measured by means of ELISA. The estimated decline in lung function was calculated from the relationship between postbronchodilator FEV1/vital capacity (percent predicted) and the duration of asthma and expressed as the slope of the regression line. Results: Patients with adult-onset nonatopic asthma and positive IgG antibodies to C pneumoniae had a significantly steeper slope of the regression line compared with the other subgroups of asthmatic patients (P = .001), being indicative of a 4-fold greater estimated decline in postbronchodilator FEV1/vital capacity (2.3% vs 0.5% predicted per year of asthma duration). Conclusion: These results suggest that C pneumoniae infection might promote the development of persistent airflow limitation in patients with nonatopic adult-onset asthma. It remains to be established whether viable pathogens that are accessible for therapeutic intervention are still present in the lower airways.. asthma| severity of illness index| airway obstruction| prognosis| chronic disease| phenotype| chlamydia pneumoniae| infection| immunology| human|air-flow obstruction| bronchoalveolar lavage| lung-function| pulmonary-disease| intrinsic asthma| peripheral-blood| bronchial-asthma| follow-up| antibodies| immunopathology.	MAR-2001	asthma| severity of illness index| airway obstruction| prognosis| chronic disease| phenotype| chlamydia pneumoniae| infection| immunology| human|air-flow obstruction| bronchoalveolar lavage| lung-function| pulmonary-disease| intrinsic asthma| peripheral-blood| bronchial-asthma| follow-up| antibodies| immunopathology	ten Brinke, A; van Dissel, JT; Sterk, PJ; Zwinderman, AH; Rabe, KF; Bel, EH	Persistent airflow limitation in adult-onset nonatopic asthma is associated with serologic evidence of Chlamydia pneumoniae infection		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; severity of illness index; airway obstruction; prognosis; chronic disease; phenotype; Chlamydia pneumoniae; infection; immunology; human	AIR-FLOW OBSTRUCTION; BRONCHOALVEOLAR LAVAGE; LUNG-FUNCTION; PULMONARY-DISEASE; INTRINSIC ASTHMA; PERIPHERAL-BLOOD; BRONCHIAL-ASTHMA; FOLLOW-UP; ANTIBODIES; IMMUNOPATHOLOGY	Background: Persistent airflow limitation may develop in patients with asthma, particularly in adults with nonatopic (intrinsic) disease. Although the underlying mechanisms are still unknown, respiratory infections might be involved. Objective: We investigated the annual loss of lung function in relation to seropositivity to Chlamydia pneumoniae in different subgroups of patients with severe asthma according to age at onset of asthma and atopic status. Methods: One hundred one nonsmoking outpatients with a pulmonologist's diagnosis of severe asthma (32 men and 69 women; mean age, 46.0 years; range, 18-75 years) were included in a cross-sectional study. C pneumoniae-specific serum IgG and IgA were measured by means of ELISA. The estimated decline in lung function was calculated from the relationship between postbronchodilator FEV1/vital capacity (percent predicted) and the duration of asthma and expressed as the slope of the regression line. Results: Patients with adult-onset nonatopic asthma and positive IgG antibodies to C pneumoniae had a significantly steeper slope of the regression line compared with the other subgroups of asthmatic patients (P = .001), being indicative of a 4-fold greater estimated decline in postbronchodilator FEV1/vital capacity (2.3% vs 0.5% predicted per year of asthma duration). Conclusion: These results suggest that C pneumoniae infection might promote the development of persistent airflow limitation in patients with nonatopic adult-onset asthma. It remains to be established whether viable pathogens that are accessible for therapeutic intervention are still present in the lower airways.	33	93	2001	6	10.1067/mai.2001.113047	Allergy; Immunology
Exposure assessment of indoor allergens, endotoxin, and airborne fungi for homes in southern Taiwan. This study was undertaken to examine the seasonal variations of domestic Der p 1, Der p 2, and endotoxin on mattress and airborne fungal concentrations in homes of asthmatic and nonasthmatic children in southern Taiwan, where temperature and relative humidity are usually high throughout the year. A group of asthmatic children (10-12 years old) were selected randomly based on a citywide questionnaire survey. The nonasthmatic children were chosen to be in the comparison group by matching in age, gender, and proximity of residence. Environmental sampling of domestic microbes was conducted once a month for a year, Twelve calendar months were grouped into spring, summer, fall, and winter according to weather data (mainly average temperature and humidity) from the Central Weather Bureau. Dust samples from a child's mattress and airborne samples fi om a child's bedroom were collected and analyzed for allergens of Der p 1 and Der p 2, endotoxin, and fungi respectively. Results show that about 65% of children's mattresses in our region have Der p 1 levels greater than 2 mug/g. It is also apparent that most airborne fungal concentrations found in homes of either asthmatic or nonasthmatic children are higher than the recommended levels of concern. The predominant genera are Cladosporium, Aspergillus, Penicillium, Alternaria, and yeast, In addition, seasonal effects seem to be a critical factor for the concentrations and distributions of domestic endotoxin in these study homes. The implication of long-term exposure to these high levels of environmental microbes and how their effects vary with seasons remain to be further characterized. (C) 2001 Academic Press.. airborne fungi| allergen| endotoxin| der p 1| der p 2|dust mite allergens| residential characteristics| control children| risk-factors| environmental exposure| domestic interiors| childhood asthma| young-adults| sensitization| prevalence.	FEB-2001	airborne fungi| allergen| endotoxin| der p 1| der p 2|dust mite allergens| residential characteristics| control children| risk-factors| environmental exposure| domestic interiors| childhood asthma| young-adults| sensitization| prevalence	Su, HJ; Wu, PC; Chen, HL; Lee, FC; Lin, LL	Exposure assessment of indoor allergens, endotoxin, and airborne fungi for homes in southern Taiwan		ENVIRONMENTAL RESEARCH	airborne fungi; allergen; endotoxin; Der p 1; Der p 2	DUST MITE ALLERGENS; RESIDENTIAL CHARACTERISTICS; CONTROL CHILDREN; RISK-FACTORS; ENVIRONMENTAL EXPOSURE; DOMESTIC INTERIORS; CHILDHOOD ASTHMA; YOUNG-ADULTS; SENSITIZATION; PREVALENCE	This study was undertaken to examine the seasonal variations of domestic Der p 1, Der p 2, and endotoxin on mattress and airborne fungal concentrations in homes of asthmatic and nonasthmatic children in southern Taiwan, where temperature and relative humidity are usually high throughout the year. A group of asthmatic children (10-12 years old) were selected randomly based on a citywide questionnaire survey. The nonasthmatic children were chosen to be in the comparison group by matching in age, gender, and proximity of residence. Environmental sampling of domestic microbes was conducted once a month for a year, Twelve calendar months were grouped into spring, summer, fall, and winter according to weather data (mainly average temperature and humidity) from the Central Weather Bureau. Dust samples from a child's mattress and airborne samples fi om a child's bedroom were collected and analyzed for allergens of Der p 1 and Der p 2, endotoxin, and fungi respectively. Results show that about 65% of children's mattresses in our region have Der p 1 levels greater than 2 mug/g. It is also apparent that most airborne fungal concentrations found in homes of either asthmatic or nonasthmatic children are higher than the recommended levels of concern. The predominant genera are Cladosporium, Aspergillus, Penicillium, Alternaria, and yeast, In addition, seasonal effects seem to be a critical factor for the concentrations and distributions of domestic endotoxin in these study homes. The implication of long-term exposure to these high levels of environmental microbes and how their effects vary with seasons remain to be further characterized. (C) 2001 Academic Press.	72	93	2001	10	10.1006/enrs.2000.4113	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
The frequency of fragrance allergy in a patch-test population over a 17-year period. Fragrances are widely encountered in our daily environment and are known to be a common cause of allergic contact dermatitis. We have reviewed our patch test data from 1980 to 1996 to establish whether the pattern of fragrance allergy has changed with time. During this period, 25,545 patients (10,450 male, 15,005 female) were patch tested with the European standard series, The mean annual frequency of positive reactions to the fragrance mix was 8.5% in females (range 6.1-10.9) and 6.7% in males (range 5.1-12.9). Females were 1.3 times more Likely to be allergic to fragrance (P < 0.001, 95% confidence interval, CI 1.17-1.41). Males with fragrance allergy were older than females by 5.6 years (mean age 48.2 vs. 42.6 years; P ( 0.001, 95% CI 3.9-7.3). The incidence of a concomitant positive patch test to balsam of Peru in fragrance-sensitive patients showed wide variation. suggesting that it is not a reliable marker of fragrance allergy, There was a positive correlation between the isomers isoeugenol and eugenol, Oak moss remained the most common overall allergen throughout the study, positive in 38.3% of females and 35.6% of males who were tested to the constituents of the fragrance mix. During the period of the study the incidence of positive tests to oak moss increased by 5% yearly (P = 0.001, 95% CI 3.2-8.7). The frequency of allergic reactions to eugenol and geraniol remained relatively constant. Isoeugenol and alpha-amyl cinnamic aldehyde sensitivity increased and hydroxycitronellal showed a slow decline. There was a striking reduction in the frequency of sensitivity to cinnamic aldehyde (by 18% yearly; P < 0.001, 95% CI 14.3-21.0) and cinnamic alcohol. (by 9% yearly; P < 0.001, 95% CI 5.2-12.9): these are now uncommon fragrance allergens. These data show temporal trends which may reflect the frequency of population exposure to individual fragrances.. allergic contact dermatitis| cosmetic allergy| fragrances| patch testing| perfumes|contact-dermatitis| constituents| mix| perfumes.	FEB-2000	allergic contact dermatitis| cosmetic allergy| fragrances| patch testing| perfumes|contact-dermatitis| constituents| mix| perfumes	Buckley, DA; Wakelin, SH; Seed, PT; Holloway, D; Rycroft, RJG; White, IR; McFadden, JP	The frequency of fragrance allergy in a patch-test population over a 17-year period		BRITISH JOURNAL OF DERMATOLOGY	allergic contact dermatitis; cosmetic allergy; fragrances; patch testing; perfumes	CONTACT-DERMATITIS; CONSTITUENTS; MIX; PERFUMES	Fragrances are widely encountered in our daily environment and are known to be a common cause of allergic contact dermatitis. We have reviewed our patch test data from 1980 to 1996 to establish whether the pattern of fragrance allergy has changed with time. During this period, 25,545 patients (10,450 male, 15,005 female) were patch tested with the European standard series, The mean annual frequency of positive reactions to the fragrance mix was 8.5% in females (range 6.1-10.9) and 6.7% in males (range 5.1-12.9). Females were 1.3 times more Likely to be allergic to fragrance (P < 0.001, 95% confidence interval, CI 1.17-1.41). Males with fragrance allergy were older than females by 5.6 years (mean age 48.2 vs. 42.6 years; P ( 0.001, 95% CI 3.9-7.3). The incidence of a concomitant positive patch test to balsam of Peru in fragrance-sensitive patients showed wide variation. suggesting that it is not a reliable marker of fragrance allergy, There was a positive correlation between the isomers isoeugenol and eugenol, Oak moss remained the most common overall allergen throughout the study, positive in 38.3% of females and 35.6% of males who were tested to the constituents of the fragrance mix. During the period of the study the incidence of positive tests to oak moss increased by 5% yearly (P = 0.001, 95% CI 3.2-8.7). The frequency of allergic reactions to eugenol and geraniol remained relatively constant. Isoeugenol and alpha-amyl cinnamic aldehyde sensitivity increased and hydroxycitronellal showed a slow decline. There was a striking reduction in the frequency of sensitivity to cinnamic aldehyde (by 18% yearly; P < 0.001, 95% CI 14.3-21.0) and cinnamic alcohol. (by 9% yearly; P < 0.001, 95% CI 5.2-12.9): these are now uncommon fragrance allergens. These data show temporal trends which may reflect the frequency of population exposure to individual fragrances.	21	93	2000	5	10.1046/j.1365-2133.2000.03298.x	Dermatology
Diagnostic Performance of an Electronic Nose, Fractional Exhaled Nitric Oxide, and Lung Function Testing in Asthma. Background: Analysis of exhaled breath by biosensors discriminates between patients with asthma and healthy subjects. An electronic nose consists of a chemical sensor array for the detection of volatile organic compounds (VOCs) and an algorithm for pattern recognition. We compared the diagnostic performance of a prototype of an electronic nose with lung function tests and fractional exhaled nitric oxide (FENO) in patients with atopic asthma. Methods: A cross-sectional study was undertaken in 27 patients with intermittent and persistent mild asthma and in 24 healthy subjects. Two procedures for collecting exhaled breath were followed to study the differences between total and alveolar air. Seven patients with asthma and seven healthy subjects participated in a study with mass spectrometry (MS) fingerprinting as an independent technique for assessing between group discrimination. Classification was based on principal component analysis and a feed-forward neural network. Results: The best results were obtained when the electronic nose analysis was performed on alveolar air. Diagnostic performance for electronic nose, FENO, and lung function testing was 87.5%, 79.2%, and 70.8%, respectively. The combination of electronic nose and FENO had the highest diagnostic performance for asthma (95.8%). MS fingerprints of VOCs could discriminate between patients with asthma and healthy subjects. Conclusions: The electronic nose has a high diagnostic performance that can be increased when combined with FENO. Large studies are now required to definitively establish the diagnostic performance of the electronic nose. Whether this integrated noninvasive approach will translate into an early diagnosis of asthma has to be clarified. Trial registration: EUDRACT https://eudralink.emea.europa.eu; Identifier: 2007-000890-51; and clinicaltrials.gov; Identifier: NCT00819676. CHEST 2010; 137(4):790-796. volatile organic-compounds| sensor array| breath| identification| cancer| metalloporphyrins| discrimination| children.	APR-2010	volatile organic-compounds| sensor array| breath| identification| cancer| metalloporphyrins| discrimination| children	Montuschi, P; Santonico, M; Mondino, C; Pennazza, G; Mantini, G; Martinelli, E; Capuano, R; Ciabattoni, G; Paolesse, R; Di Natale, C; Barnes, PJ; D'Amico, A	Diagnostic Performance of an Electronic Nose, Fractional Exhaled Nitric Oxide, and Lung Function Testing in Asthma		CHEST		VOLATILE ORGANIC-COMPOUNDS; SENSOR ARRAY; BREATH; IDENTIFICATION; CANCER; METALLOPORPHYRINS; DISCRIMINATION; CHILDREN	Background: Analysis of exhaled breath by biosensors discriminates between patients with asthma and healthy subjects. An electronic nose consists of a chemical sensor array for the detection of volatile organic compounds (VOCs) and an algorithm for pattern recognition. We compared the diagnostic performance of a prototype of an electronic nose with lung function tests and fractional exhaled nitric oxide (FENO) in patients with atopic asthma. Methods: A cross-sectional study was undertaken in 27 patients with intermittent and persistent mild asthma and in 24 healthy subjects. Two procedures for collecting exhaled breath were followed to study the differences between total and alveolar air. Seven patients with asthma and seven healthy subjects participated in a study with mass spectrometry (MS) fingerprinting as an independent technique for assessing between group discrimination. Classification was based on principal component analysis and a feed-forward neural network. Results: The best results were obtained when the electronic nose analysis was performed on alveolar air. Diagnostic performance for electronic nose, FENO, and lung function testing was 87.5%, 79.2%, and 70.8%, respectively. The combination of electronic nose and FENO had the highest diagnostic performance for asthma (95.8%). MS fingerprints of VOCs could discriminate between patients with asthma and healthy subjects. Conclusions: The electronic nose has a high diagnostic performance that can be increased when combined with FENO. Large studies are now required to definitively establish the diagnostic performance of the electronic nose. Whether this integrated noninvasive approach will translate into an early diagnosis of asthma has to be clarified. Trial registration: EUDRACT https://eudralink.emea.europa.eu; Identifier: 2007-000890-51; and clinicaltrials.gov; Identifier: NCT00819676. CHEST 2010; 137(4):790-796	25	92	2010	7	10.1378/chest.09-1836	General & Internal Medicine; Respiratory System
Injection allergen immunotherapy for asthma. Background Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and methods of delivery, we updated the systematic review of allergen specific immunotherapy for asthma. Objectives The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. Search strategy We searched the Cochrane Airways Group Trials Register up to 2005, Dissertation Abstracts and Current Contents. Selection criteria Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. Data collection and analysis Three authors independently assessed eligibility of studies for inclusion. Two authors independently performed quality assessment of studies. Main results Eighty-eight trials were included (13 new trials). There were 42 trials of immunotherapy for house mite allergy; 27 pollen allergy trials; 10 animal dander allergy trials; two Cladosporium mould allergy, two latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 16 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication, and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardised mean difference -0.59, 95% confidence interval -0.83 to -0.35) and it would have been necessary to treat three patients (95% CI 3 to 5) with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat four patients (95% CI 3 to 6) with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. If 16 patients were treated with immunotherapy, one would be expected to develop a local adverse reaction. If nine patients were treated with immunotherapy, one would be expected to develop a systemic reaction (of any severity). Authors' conclusions Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.. *desensitization, immunologic| allergens [administration & dosage| immunology]| asthma [immunology| *therapy]| injections, subcutaneous| randomized controlled trials as topic| humans|house-dust-mite| placebo-controlled trial| double-blind placebo| dermatophagoides-pteronyssinus extract| sublingual-swallow immunotherapy| grass-pollen immunotherapy| 3-year double-blind| standardized 5-grass-pollen extract| enzyme-potentiated desensitization| randomized controlled-trial.	2010	*desensitization, immunologic| allergens [administration & dosage| immunology]| asthma [immunology| *therapy]| injections, subcutaneous| randomized controlled trials as topic| humans|house-dust-mite| placebo-controlled trial| double-blind placebo| dermatophagoides-pteronyssinus extract| sublingual-swallow immunotherapy| grass-pollen immunotherapy| 3-year double-blind| standardized 5-grass-pollen extract| enzyme-potentiated desensitization| randomized controlled-trial	Abramson, MJ; Puy, RM; Weiner, JM	Injection allergen immunotherapy for asthma		COCHRANE DATABASE OF SYSTEMATIC REVIEWS	*Desensitization, Immunologic; Allergens [administration & dosage; immunology]; Asthma [immunology; *therapy]; Injections, Subcutaneous; Randomized Controlled Trials as Topic; Humans	HOUSE-DUST-MITE; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND PLACEBO; DERMATOPHAGOIDES-PTERONYSSINUS EXTRACT; SUBLINGUAL-SWALLOW IMMUNOTHERAPY; GRASS-POLLEN IMMUNOTHERAPY; 3-YEAR DOUBLE-BLIND; STANDARDIZED 5-GRASS-POLLEN EXTRACT; ENZYME-POTENTIATED DESENSITIZATION; RANDOMIZED CONTROLLED-TRIAL	Background Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and methods of delivery, we updated the systematic review of allergen specific immunotherapy for asthma. Objectives The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. Search strategy We searched the Cochrane Airways Group Trials Register up to 2005, Dissertation Abstracts and Current Contents. Selection criteria Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. Data collection and analysis Three authors independently assessed eligibility of studies for inclusion. Two authors independently performed quality assessment of studies. Main results Eighty-eight trials were included (13 new trials). There were 42 trials of immunotherapy for house mite allergy; 27 pollen allergy trials; 10 animal dander allergy trials; two Cladosporium mould allergy, two latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 16 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication, and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardised mean difference -0.59, 95% confidence interval -0.83 to -0.35) and it would have been necessary to treat three patients (95% CI 3 to 5) with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat four patients (95% CI 3 to 6) with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. If 16 patients were treated with immunotherapy, one would be expected to develop a local adverse reaction. If nine patients were treated with immunotherapy, one would be expected to develop a systemic reaction (of any severity). Authors' conclusions Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.	349	92	2010	111	10.1002/14651858.CD001186.pub2	General & Internal Medicine
Residential proximity fine particles related to allergic sensitisation and asthma in primary school children. Background: Fine particulate matter has been linked to allergies by experimental and epidemiological data having used aggregated data or concentrations provided by fixed-site monitoring stations, which may have led to misclassification of individual exposure to air pollution. Methods: A semi-individual design was employed to relate individual data on asthma and allergy of 5338 school children (10.4 +/- 0.7 years) attending 108 randomly chosen schools in 6 French cities to the concentrations of PM2.5 (fine particles with aerodynamic diameter <= 2.5 mu m) assessed in proximity of their homes. Children underwent a medical visit including skin prick test (SPT) to common allergens, exercise-induced bronchial (EIB) reactivity and skin examination for flexural dermatitis. Their parents fitted in a standardised health questionnaire. Results: After adjustment for confounders and NO2 as a potential modifier, the odds of suffering from EIB and flexural dermatitis at the period of the survey, past year atopic asthma and SPT positivity to indoor allergens were significantly increased in residential settings with PM2.5 concentrations exceeding 10 mu g/m(3) (WHO air quality limit values). The relationships were strengthened in long-term residents (current address for at least 8 years). Conclusions: Findings support the hypothesis that changes in allergy prevalence observed in recent decades might be partly related to interactions between traffic-related air pollution and allergens. Further longitudinal investigations are needed to corroborate such results. (c) 2007 Elsevier Ltd. All rights reserved.. air pollution| asthma| allergic rhinitis| traffic| no2| pm2.5|diesel exhaust particles| air-pollution| respiratory health| exposure| pollutants| atopy| ige| schoolchildren| inflammation| particulate.	AUG-2007	air pollution| asthma| allergic rhinitis| traffic| no2| pm2.5|diesel exhaust particles| air-pollution| respiratory health| exposure| pollutants| atopy| ige| schoolchildren| inflammation| particulate	Annesi-Maesano, I; Moreau, D; Caillaud, D; Lavaud, F; Le Moullec, Y; Taytard, A; Pauli, G; Charpin, D	Residential proximity fine particles related to allergic sensitisation and asthma in primary school children		RESPIRATORY MEDICINE	air pollution; asthma; allergic rhinitis; traffic; NO2; PM2.5	DIESEL EXHAUST PARTICLES; AIR-POLLUTION; RESPIRATORY HEALTH; EXPOSURE; POLLUTANTS; ATOPY; IGE; SCHOOLCHILDREN; INFLAMMATION; PARTICULATE	Background: Fine particulate matter has been linked to allergies by experimental and epidemiological data having used aggregated data or concentrations provided by fixed-site monitoring stations, which may have led to misclassification of individual exposure to air pollution. Methods: A semi-individual design was employed to relate individual data on asthma and allergy of 5338 school children (10.4 +/- 0.7 years) attending 108 randomly chosen schools in 6 French cities to the concentrations of PM2.5 (fine particles with aerodynamic diameter <= 2.5 mu m) assessed in proximity of their homes. Children underwent a medical visit including skin prick test (SPT) to common allergens, exercise-induced bronchial (EIB) reactivity and skin examination for flexural dermatitis. Their parents fitted in a standardised health questionnaire. Results: After adjustment for confounders and NO2 as a potential modifier, the odds of suffering from EIB and flexural dermatitis at the period of the survey, past year atopic asthma and SPT positivity to indoor allergens were significantly increased in residential settings with PM2.5 concentrations exceeding 10 mu g/m(3) (WHO air quality limit values). The relationships were strengthened in long-term residents (current address for at least 8 years). Conclusions: Findings support the hypothesis that changes in allergy prevalence observed in recent decades might be partly related to interactions between traffic-related air pollution and allergens. Further longitudinal investigations are needed to corroborate such results. (c) 2007 Elsevier Ltd. All rights reserved.	38	92	2007	9	10.1016/j.rmed.2007.02.022	Cardiovascular System & Cardiology; Respiratory System
The comparative immunotoxicity of five selected compounds following developmental or adult exposure. It is well established that human diseases associated with abnormal immune function, including some common infectious diseases and asthma, are considerably more prevalent at younger ages. Although not established absolutely, it is generally believed that development constitutes a period of increased immune system susceptibility to xenobiotics, since adverse effects may occur at lower doses and/or immunomodulation may be more persistent, thus increasing the relative risk of xenobiotic exposure to the immunologically immature organism. To address this issue, a brief overview of immune maturation in humans is provided to demonstrate that functional immaturity alone predisposes the young to infection. Age-dependent differences in the immunotoxic effects of five diverse compounds, diethylstilbestrol (DES), diazepam (DZP), lead (Pb), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and tributyltin oxide (TBTO), which have undergone adult and developmental immunotoxicity testing in rodents, are then reviewed, as are human data when available. For all five chemicals, the developing immune system was found to be at greater risk than that of the adult, either because lower doses produced immunotoxicity, adverse effects were more persistent, or both.. delayed-type hypersensitivity| developing immune-system| tetrachlorodibenzo-p-dioxin| prenatal diazepam exposure| natural-killer-cells| humoral immunity| 2,3,7,8-tetrachlorodibenzo-p-dioxin tcdd| perinatal exposure| host-resistance| lead-exposure.	JAN-FEB-2006	delayed-type hypersensitivity| developing immune-system| tetrachlorodibenzo-p-dioxin| prenatal diazepam exposure| natural-killer-cells| humoral immunity| 2,3,7,8-tetrachlorodibenzo-p-dioxin tcdd| perinatal exposure| host-resistance| lead-exposure	Luebke, RW; Chen, DH; Dietert, R; Yang, Y; King, M; Luster, MI	The comparative immunotoxicity of five selected compounds following developmental or adult exposure		JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS		DELAYED-TYPE HYPERSENSITIVITY; DEVELOPING IMMUNE-SYSTEM; TETRACHLORODIBENZO-P-DIOXIN; PRENATAL DIAZEPAM EXPOSURE; NATURAL-KILLER-CELLS; HUMORAL IMMUNITY; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; PERINATAL EXPOSURE; HOST-RESISTANCE; LEAD-EXPOSURE	It is well established that human diseases associated with abnormal immune function, including some common infectious diseases and asthma, are considerably more prevalent at younger ages. Although not established absolutely, it is generally believed that development constitutes a period of increased immune system susceptibility to xenobiotics, since adverse effects may occur at lower doses and/or immunomodulation may be more persistent, thus increasing the relative risk of xenobiotic exposure to the immunologically immature organism. To address this issue, a brief overview of immune maturation in humans is provided to demonstrate that functional immaturity alone predisposes the young to infection. Age-dependent differences in the immunotoxic effects of five diverse compounds, diethylstilbestrol (DES), diazepam (DZP), lead (Pb), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and tributyltin oxide (TBTO), which have undergone adult and developmental immunotoxicity testing in rodents, are then reviewed, as are human data when available. For all five chemicals, the developing immune system was found to be at greater risk than that of the adult, either because lower doses produced immunotoxicity, adverse effects were more persistent, or both.	116	92	2006	26	10.1080/15287390500194326	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
IL-19 induced Th2 cytokines and was up-regulated in asthma patients. IL-19 belongs to the IL-10 family, which includes IL-10, IL-19, IL-20, IL-22, melanoma differentiation-associated gene-7 (IL-24), and AK155 (IL-26). IL-10 has been shown to inhibit allergen-induced airway hyperreactivity and inflammation. To determine whether IL-19 was also associated with asthma, we used ELISA to analyze the serum level of IL-19 in patients with asthma and found that their serum IL-19 levels were twice those of healthy controls. Patients with a high level of IL-19 also had high levels of IL-4 and IL-13. In a dust mite-induced murine model of asthma, we found that IL-19 level in asthmatic BALB/cJ mice was also twice that of healthy control mice. IL-19 transcript was also induced in the lungs of asthmatic mice. Electroporation i.m. of the IL-19 gene into healthy mice up-regulated IL-4 and IL-5, but not IL-13. However, IL-19 up-regulated IL-13 in asthmatic mice. In vitro, IL-19 induced IL-4, IL-5, IL-10, and IL-13 production by activated T cells. Activation of T cells was required for induction of IL-13 because IL-19 did not induce IL-13 production on nonstimulated T cells. Taken together, these results demonstrated that IL-19 up-regulates Th2 cytokines on activated T cells and might play an important role in the pathogenesis of asthma.. human interleukin-10| stimulatory factor| transgenic mice| murine model| t-cells| inflammation| responses| determines| induction| effectors.	DEC 1-2004	human interleukin-10| stimulatory factor| transgenic mice| murine model| t-cells| inflammation| responses| determines| induction| effectors	Liao, SC; Cheng, YC; Wang, YC; Wang, CW; Yang, SM; Yu, CK; Shieh, CC; Cheng, KC; Lee, MF; Chiang, SR; Shieh, JM; Chang, MS	IL-19 induced Th2 cytokines and was up-regulated in asthma patients		JOURNAL OF IMMUNOLOGY		HUMAN INTERLEUKIN-10; STIMULATORY FACTOR; TRANSGENIC MICE; MURINE MODEL; T-CELLS; INFLAMMATION; RESPONSES; DETERMINES; INDUCTION; EFFECTORS	IL-19 belongs to the IL-10 family, which includes IL-10, IL-19, IL-20, IL-22, melanoma differentiation-associated gene-7 (IL-24), and AK155 (IL-26). IL-10 has been shown to inhibit allergen-induced airway hyperreactivity and inflammation. To determine whether IL-19 was also associated with asthma, we used ELISA to analyze the serum level of IL-19 in patients with asthma and found that their serum IL-19 levels were twice those of healthy controls. Patients with a high level of IL-19 also had high levels of IL-4 and IL-13. In a dust mite-induced murine model of asthma, we found that IL-19 level in asthmatic BALB/cJ mice was also twice that of healthy control mice. IL-19 transcript was also induced in the lungs of asthmatic mice. Electroporation i.m. of the IL-19 gene into healthy mice up-regulated IL-4 and IL-5, but not IL-13. However, IL-19 up-regulated IL-13 in asthmatic mice. In vitro, IL-19 induced IL-4, IL-5, IL-10, and IL-13 production by activated T cells. Activation of T cells was required for induction of IL-13 because IL-19 did not induce IL-13 production on nonstimulated T cells. Taken together, these results demonstrated that IL-19 up-regulates Th2 cytokines on activated T cells and might play an important role in the pathogenesis of asthma.	25	92	2004	7		Immunology
Novel alternative methods for the delivery of drugs for the treatment of asthma. Successful delivery of dry powder aerosols to the lung requires careful consideration of the powder production process, formulation and inhaler device. Newer production methods are emerging to prepare powders with desirable characteristics for inhalational administration. The conventional formulation approach of adding coarse lactose carriers to the drug to form binary powder systems to enhance powder flow and dispersion properties has been expanded to using finer carrier particles and hydrophobic materials, as well as ternary systems. Particle morphology and surface properties have also been explored to enhance powder performance. For the inhaler device, the new generation inhalers are designed to reduce or completely decouple the influence of air flow on the aerosol generation. Each of these determinants for powder aerosol delivery is reviewed with a strong focus on the patent literature that contains enormous information about the latest development in this field. (C) 2003 Elsevier Science B.V. All rights reserved.. dry powder aerosol formulation| powder production process| spray drying| solvent precipitation| milling| powder properties| carrier blend| dry powder inhaler|salbutamol sulfate| porous particles| inhalation| formulations| powders| carrier| lactose.	JUL 18-2003	dry powder aerosol formulation| powder production process| spray drying| solvent precipitation| milling| powder properties| carrier blend| dry powder inhaler|salbutamol sulfate| porous particles| inhalation| formulations| powders| carrier| lactose	Chan, HK; Chew, NYK	Novel alternative methods for the delivery of drugs for the treatment of asthma		ADVANCED DRUG DELIVERY REVIEWS	dry powder aerosol formulation; powder production process; spray drying; solvent precipitation; milling; powder properties; carrier blend; dry powder inhaler	SALBUTAMOL SULFATE; POROUS PARTICLES; INHALATION; FORMULATIONS; POWDERS; CARRIER; LACTOSE	Successful delivery of dry powder aerosols to the lung requires careful consideration of the powder production process, formulation and inhaler device. Newer production methods are emerging to prepare powders with desirable characteristics for inhalational administration. The conventional formulation approach of adding coarse lactose carriers to the drug to form binary powder systems to enhance powder flow and dispersion properties has been expanded to using finer carrier particles and hydrophobic materials, as well as ternary systems. Particle morphology and surface properties have also been explored to enhance powder performance. For the inhaler device, the new generation inhalers are designed to reduce or completely decouple the influence of air flow on the aerosol generation. Each of these determinants for powder aerosol delivery is reviewed with a strong focus on the patent literature that contains enormous information about the latest development in this field. (C) 2003 Elsevier Science B.V. All rights reserved.	69	92	2003	13	10.1016/S0169-409X(03)00078-4	Pharmacology & Pharmacy
Indoor aldehydes: measurement of contamination levels and identification of their determinants in Paris dwellings. The recent increased prevalence of childhood asthma and atopy has brought into question the impact of outdoor pollutants and indoor air quality. The contributory role of aldehydes to this problem and the fact that they are mainly derived from the domestic environment make them of particular interest. This study therefore measures six different aldehyde levels in Paris dwellings from potentially different sources and identifies their indoor determinants. The study was carried out in the three principal rooms of 61 flats with no previous history of complaint for olfactory nuisance or specific symptoms, two-thirds of the flats having been recently refurbished. Aldehydes were sampled in these rooms using passive samplers, and a questionnaire on potential aldehyde sources was filled out at the same time. A multiple linear regression model was used to investigate indoor aldehyde determinants. Our study revealed that propionaldehyde and benzaldehyde were of minor importance compared to formaldehyde, acetaldehyde, pentanal, and hexanal. We found that levels of these last four compounds depended on the age of wall or floor coverings (renovations less than I year old), smoking, and ambient parameters (carbon dioxide levels, temperature). These results could help in the assessment of ndoor aldehyde emissions. (C) 2003 Elsevier Science (USA). All rights reserved.. aldehyde| indoor air quality| determinants| passive sampling| ventilation|formaldehyde concentrations| exposure| air| environments| tobacco| health.	JUL-2003	aldehyde| indoor air quality| determinants| passive sampling| ventilation|formaldehyde concentrations| exposure| air| environments| tobacco| health	Clarisse, B; Laurent, AM; Seta, N; Le Moullec, Y; El Hasnaoui, A; Momas, I	Indoor aldehydes: measurement of contamination levels and identification of their determinants in Paris dwellings		ENVIRONMENTAL RESEARCH	aldehyde; indoor air quality; determinants; passive sampling; ventilation	FORMALDEHYDE CONCENTRATIONS; EXPOSURE; AIR; ENVIRONMENTS; TOBACCO; HEALTH	The recent increased prevalence of childhood asthma and atopy has brought into question the impact of outdoor pollutants and indoor air quality. The contributory role of aldehydes to this problem and the fact that they are mainly derived from the domestic environment make them of particular interest. This study therefore measures six different aldehyde levels in Paris dwellings from potentially different sources and identifies their indoor determinants. The study was carried out in the three principal rooms of 61 flats with no previous history of complaint for olfactory nuisance or specific symptoms, two-thirds of the flats having been recently refurbished. Aldehydes were sampled in these rooms using passive samplers, and a questionnaire on potential aldehyde sources was filled out at the same time. A multiple linear regression model was used to investigate indoor aldehyde determinants. Our study revealed that propionaldehyde and benzaldehyde were of minor importance compared to formaldehyde, acetaldehyde, pentanal, and hexanal. We found that levels of these last four compounds depended on the age of wall or floor coverings (renovations less than I year old), smoking, and ambient parameters (carbon dioxide levels, temperature). These results could help in the assessment of ndoor aldehyde emissions. (C) 2003 Elsevier Science (USA). All rights reserved.	26	92	2003	9	10.1016/S0013-9351(03)00039-2	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Who gets diagnosed with asthma? Frequent wheeze among adolescents with and without a diagnosis of asthma. Objective. 1) To describe the factors associated with not receiving an asthma diagnosis among children with frequent wheezing symptoms and 2) to determine risk factors for frequent wheezing in the population. Methods. The North Carolina School Asthma Survey provided self-reported questionnaire data on respiratory health from 122 829 children ages 12 to 18 years enrolled in 499 public middle schools in North Carolina during the 1999 - 2000 school year. Questions from the International Survey of Allergies and Asthma in Childhood were used to estimate the prevalence of asthma and wheezing-related illness and associated factors. Results. Factors independently associated with undiagnosed frequent wheezing versus asymptomatic children included female gender ( odds ratio [ OR]: 1.45; 95% confidence interval [CI]: 1.35-1.54), current smoking ( OR: 2.60; 95% CI: 2.43-2.79), exposure to household smoke ( OR: 1.59; 95% CI: 1.50-1.70), low socioeconomic status ( OR: 1.52; 95% CI: 1.42-1.63), and African American ( OR: 1.25; 95% CI: 1.15-1.34), Native American ( OR: 1.35; 95% CI: 1.11-1.62), and Mexican American ( OR: 1.32; 95% CI: 1.17-1.48) race/ethnicity. Urban residence showed a weak negative association ( OR: 0.91; 95% CI: 0.85-0.96). A similar pattern of results was observed for analyses comparing odds of undiagnosed frequent wheeze versus diagnosed asthmatics. Report of allergies was less likely in frequent wheezers (70%) compared with diagnosed asthmatics (86%), but much higher than in asymptomatic children (36%). Thirty-three percent of children with undiagnosed frequent wheezing reported 1 or more physician visits in the last year for wheezing or breathing problems compared with 71% of children with diagnosed asthma, and 4% in asymptomatic children. The prevalence of any inhaler use in the past 12 months was 12% for undiagnosed frequent wheezers versus 78% for diagnosed asthmatics. The proportion of undiagnosed frequent wheezers with fair or poor self-rated health (23%) was slightly higher than diagnosed asthmatics (20%) and much higher than asymptomatic children ( 4%). Conclusions. In one of the largest adolescent asthma surveys ever reported in the United States, undiagnosed frequent wheezing was independently associated with female gender, current smoking, exposure to household smoke, low socioeconomic status, allergies, and African American, Native American, and Mexican American race/ ethnicity. Children with undiagnosed frequent wheezing were not receiving adequate health care for their asthma-like illness. Clinicians who treat adolescents should consider asking adolescents specifically about wheezing. This information may assist primary care physicians in identifying children with undiagnosed asthma in need of treatment.. asthma| adolescents| wheezing| diagnosis| demographics| allergies|childhood asthma| video questionnaire| persistent wheeze| african-american| health-services| united-states| great-britain| risk-factors| children| prevalence.	MAY 1-2003	asthma| adolescents| wheezing| diagnosis| demographics| allergies|childhood asthma| video questionnaire| persistent wheeze| african-american| health-services| united-states| great-britain| risk-factors| children| prevalence	Yeatts, K; Davis, KJ; Sotir, M; Herget, C; Shy, C	Who gets diagnosed with asthma? Frequent wheeze among adolescents with and without a diagnosis of asthma		PEDIATRICS	asthma; adolescents; wheezing; diagnosis; demographics; allergies	CHILDHOOD ASTHMA; VIDEO QUESTIONNAIRE; PERSISTENT WHEEZE; AFRICAN-AMERICAN; HEALTH-SERVICES; UNITED-STATES; GREAT-BRITAIN; RISK-FACTORS; CHILDREN; PREVALENCE	Objective. 1) To describe the factors associated with not receiving an asthma diagnosis among children with frequent wheezing symptoms and 2) to determine risk factors for frequent wheezing in the population. Methods. The North Carolina School Asthma Survey provided self-reported questionnaire data on respiratory health from 122 829 children ages 12 to 18 years enrolled in 499 public middle schools in North Carolina during the 1999 - 2000 school year. Questions from the International Survey of Allergies and Asthma in Childhood were used to estimate the prevalence of asthma and wheezing-related illness and associated factors. Results. Factors independently associated with undiagnosed frequent wheezing versus asymptomatic children included female gender ( odds ratio [ OR]: 1.45; 95% confidence interval [CI]: 1.35-1.54), current smoking ( OR: 2.60; 95% CI: 2.43-2.79), exposure to household smoke ( OR: 1.59; 95% CI: 1.50-1.70), low socioeconomic status ( OR: 1.52; 95% CI: 1.42-1.63), and African American ( OR: 1.25; 95% CI: 1.15-1.34), Native American ( OR: 1.35; 95% CI: 1.11-1.62), and Mexican American ( OR: 1.32; 95% CI: 1.17-1.48) race/ethnicity. Urban residence showed a weak negative association ( OR: 0.91; 95% CI: 0.85-0.96). A similar pattern of results was observed for analyses comparing odds of undiagnosed frequent wheeze versus diagnosed asthmatics. Report of allergies was less likely in frequent wheezers (70%) compared with diagnosed asthmatics (86%), but much higher than in asymptomatic children (36%). Thirty-three percent of children with undiagnosed frequent wheezing reported 1 or more physician visits in the last year for wheezing or breathing problems compared with 71% of children with diagnosed asthma, and 4% in asymptomatic children. The prevalence of any inhaler use in the past 12 months was 12% for undiagnosed frequent wheezers versus 78% for diagnosed asthmatics. The proportion of undiagnosed frequent wheezers with fair or poor self-rated health (23%) was slightly higher than diagnosed asthmatics (20%) and much higher than asymptomatic children ( 4%). Conclusions. In one of the largest adolescent asthma surveys ever reported in the United States, undiagnosed frequent wheezing was independently associated with female gender, current smoking, exposure to household smoke, low socioeconomic status, allergies, and African American, Native American, and Mexican American race/ ethnicity. Children with undiagnosed frequent wheezing were not receiving adequate health care for their asthma-like illness. Clinicians who treat adolescents should consider asking adolescents specifically about wheezing. This information may assist primary care physicians in identifying children with undiagnosed asthma in need of treatment.	44	92	2003	9	10.1542/peds.111.5.1046	Pediatrics
Reduced soluble CD14 levels in amniotic fluid and breast milk are associated with the subsequent development of atopy, eczema, or both. Background: Exposure to various microbial products in early life reduces the risk of atopy. Such exposure induces down-regulation of T(H)2 allergy-biased responses by means of pattern recognition molecules, such as CD14, an LPS receptor. Objective: We sought to determine whether infant and maternal levels of soluble CD14 (sCD14) are associated with the atopic outcomes of infants. Methods: Levels of sCD14 in plasma, amniotic fluid, and breast milk were measured with a specific ELISA in different cohorts. Expression of toll-like receptors in the fetal gut was examined by using RT-PCR. Results: Soluble CD14 levels increased during fetal development and postnatally, attaining adult levels by around 4 months of age, with an overshoot of adult levels from 6 months of age. There was no difference in plasma sCD14 levels at birth of children with a high compared with those with a low risk of development of atopy. Amniotic fluid sCD14 levels at midgestation (16-17 weeks) were significantly lower when the child was subsequently atopic (P < .05). Soluble CD14 levels in breast milk collected 3 months postpartum were significantly lower in children with eczema at 6 months of age, irrespective of whether they were atopic (P = .003). Transcripts for toll-like receptor 4, which would enable transmembrane signaling for LPS/sCD14 complexes, were expressed within fetal gut and skin. Conclusion: Exposure to reduced levels of sCD14 in the fetal and neonatal gastrointestinal tract is associated with the development of atopy, eczema, or both. Thus the exogenous supply of sCD14 might influence immunologic reactivity both locally and systemically in early life and thereby influence disease outcome.. soluble cd14| amniotic fluid| breast milk| eczema|early-childhood| ige production| immune-system| cutting edge| hay-fever| lipopolysaccharide| children| asthma| recognition| microflora.	MAY-2002	soluble cd14| amniotic fluid| breast milk| eczema|early-childhood| ige production| immune-system| cutting edge| hay-fever| lipopolysaccharide| children| asthma| recognition| microflora	Jones, CA; Holloway, JA; Popplewell, EJ; Diaper, ND; Holloway, JW; Vance, GHS; Warner, JA; Warner, JO	Reduced soluble CD14 levels in amniotic fluid and breast milk are associated with the subsequent development of atopy, eczema, or both		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	soluble CD14; amniotic fluid; breast milk; eczema	EARLY-CHILDHOOD; IGE PRODUCTION; IMMUNE-SYSTEM; CUTTING EDGE; HAY-FEVER; LIPOPOLYSACCHARIDE; CHILDREN; ASTHMA; RECOGNITION; MICROFLORA	Background: Exposure to various microbial products in early life reduces the risk of atopy. Such exposure induces down-regulation of T(H)2 allergy-biased responses by means of pattern recognition molecules, such as CD14, an LPS receptor. Objective: We sought to determine whether infant and maternal levels of soluble CD14 (sCD14) are associated with the atopic outcomes of infants. Methods: Levels of sCD14 in plasma, amniotic fluid, and breast milk were measured with a specific ELISA in different cohorts. Expression of toll-like receptors in the fetal gut was examined by using RT-PCR. Results: Soluble CD14 levels increased during fetal development and postnatally, attaining adult levels by around 4 months of age, with an overshoot of adult levels from 6 months of age. There was no difference in plasma sCD14 levels at birth of children with a high compared with those with a low risk of development of atopy. Amniotic fluid sCD14 levels at midgestation (16-17 weeks) were significantly lower when the child was subsequently atopic (P < .05). Soluble CD14 levels in breast milk collected 3 months postpartum were significantly lower in children with eczema at 6 months of age, irrespective of whether they were atopic (P = .003). Transcripts for toll-like receptor 4, which would enable transmembrane signaling for LPS/sCD14 complexes, were expressed within fetal gut and skin. Conclusion: Exposure to reduced levels of sCD14 in the fetal and neonatal gastrointestinal tract is associated with the development of atopy, eczema, or both. Thus the exogenous supply of sCD14 might influence immunologic reactivity both locally and systemically in early life and thereby influence disease outcome.	32	92	2002	9	10.1067/mai.2002.123535	Allergy; Immunology
Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children. Background Studies have suggested that early contact with pets may prevent the development of allergy and asthma. Objective To study the association between early, current and past pet ownership and sensitization, bronchial responsiveness and allergic symptoms in school children. Methods A population of almost 3000 primary school children was investigated using protocols of the International Study on Asthma and Allergies in Childhood (ISAAC). Allergic symptoms were measured using the parent-completed ISAAC questionnaire. Sensitization to common allergens was measured using skin prick tests (SPT)s and/or serum immunoglobulin (Ig)E determinations. Bronchial responsiveness was tested using a hypertonic saline challenge. Pet ownership was investigated by questionnaire. Current, past and early exposure to pets was documented separately for cats, dogs, rodents and birds. The data on current, past and early pet exposure were then related to allergic symptoms, sensitization and bronchial responsiveness. Results Among children currently exposed to pets, there was significantly less sensitization to cat (odds ratio (OR) = 0.69) and dog (OR = 0.63) allergens, indoor allergens in general (OR = 0.64), and outdoor allergens (OR = 0.60) compared to children who never had pets in the home. There was also less hayfever (OR=0.66) and rhinitis (OR=0.76). In contrast, wheeze, asthma and bronchial responsiveness were not associated with current pet ownership. Odds ratios associated with past pet ownership were generally above unity, and significant for asthma in the adjusted analysis (OR= 1.85), suggesting selective avoidance in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only showed an inverse association with sensitization to pollen: OR = 0.71 for having had furry or feathery pets in general in the first two years of life, and OR = 0.73 for having had cats and/or dogs in the first two years of life, compared to not having had pets in the first two years of life. Conclusion These results suggest that the inverse association between current pet ownership and sensitization and hayfever symptoms was partly due to the removal of pets in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only seemed to offer some protection against sensitization to pollen.. pets| cats| dogs| sensitization| bronchial responsiveness| asthma|hay-fever| early exposure| risk factor| asthma| atopy| farm| life| cat| environment| infections.	MAR-2002	pets| cats| dogs| sensitization| bronchial responsiveness| asthma|hay-fever| early exposure| risk factor| asthma| atopy| farm| life| cat| environment| infections	Anyo, G; Brunekreef, B; de Meer, G; Aarts, F; Janssen, NAH; van Vliet, P	Early, current and past pet ownership: associations with sensitization, bronchial responsiveness and allergic symptoms in school children		CLINICAL AND EXPERIMENTAL ALLERGY	pets; cats; dogs; sensitization; bronchial responsiveness; asthma	HAY-FEVER; EARLY EXPOSURE; RISK FACTOR; ASTHMA; ATOPY; FARM; LIFE; CAT; ENVIRONMENT; INFECTIONS	Background Studies have suggested that early contact with pets may prevent the development of allergy and asthma. Objective To study the association between early, current and past pet ownership and sensitization, bronchial responsiveness and allergic symptoms in school children. Methods A population of almost 3000 primary school children was investigated using protocols of the International Study on Asthma and Allergies in Childhood (ISAAC). Allergic symptoms were measured using the parent-completed ISAAC questionnaire. Sensitization to common allergens was measured using skin prick tests (SPT)s and/or serum immunoglobulin (Ig)E determinations. Bronchial responsiveness was tested using a hypertonic saline challenge. Pet ownership was investigated by questionnaire. Current, past and early exposure to pets was documented separately for cats, dogs, rodents and birds. The data on current, past and early pet exposure were then related to allergic symptoms, sensitization and bronchial responsiveness. Results Among children currently exposed to pets, there was significantly less sensitization to cat (odds ratio (OR) = 0.69) and dog (OR = 0.63) allergens, indoor allergens in general (OR = 0.64), and outdoor allergens (OR = 0.60) compared to children who never had pets in the home. There was also less hayfever (OR=0.66) and rhinitis (OR=0.76). In contrast, wheeze, asthma and bronchial responsiveness were not associated with current pet ownership. Odds ratios associated with past pet ownership were generally above unity, and significant for asthma in the adjusted analysis (OR= 1.85), suggesting selective avoidance in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only showed an inverse association with sensitization to pollen: OR = 0.71 for having had furry or feathery pets in general in the first two years of life, and OR = 0.73 for having had cats and/or dogs in the first two years of life, compared to not having had pets in the first two years of life. Conclusion These results suggest that the inverse association between current pet ownership and sensitization and hayfever symptoms was partly due to the removal of pets in families with sensitized and/or symptomatic children. Pet ownership in the first two years of life only seemed to offer some protection against sensitization to pollen.	26	92	2002	6	10.1046/j.1365-2222.2002.01254.x	Allergy; Immunology
The US Peanut and Tree Nut Allergy Registry: Characteristics of reactions in schools and day care. Objective: Severe food-allergic reactions occur in schools, but. the features have not been described. Study design: Participants in the US Peanut and Tree Nut Allergy Registry (PAR) who indicated that their child experienced an allergic reaction in school or day care were randomly selected for a telephone interview conducted with a structured questionnaire. Results: Of 4586 participants in the PAR, 750 (16%) indicated a reaction in school or day care, and 100 subjects or parental surrogates described 124 reactions to peanut (115) or tree nuts (9); 64% of the reactions occurred in day care or preschool, and the remainder in elementary school or higher grades. Reactions were reported from ingestion (60%), skin contact/possible ingestion (24%), and inhalation/possible skin contact or ingestion (16%). In the majority of reactions caused by inhalation, concomitant ingestion/skin contact could not be ruled out. Various foods caused by ingestion, but peanut butter crab projects were commonly responsible for the skin contact (44%) or inhalation (41%) reactions. For 90% of reactions, medications were given (86% antihistamines, 28% epinephrine). Epinephrine was given in school by teachers in 4 cases, nurses in 7, and parents or others in the remainder. Treatment delays were attributed to delayed recognition of reactions, calling parents, not following emergency plans, and an unsuccessful attempt to administer epinephrine. Conclusions: School personnel must be educated to recognize and treat food-allergic reactions. Awareness must be increased to avoid accidental exposures, including exposure from peanut butter craft projects.. double-blind| food| children| anaphylaxis| life.	APR-2001	double-blind| food| children| anaphylaxis| life	Sicherer, SH; Furlong, TJ; DeSimone, J; Sampson, HA	The US Peanut and Tree Nut Allergy Registry: Characteristics of reactions in schools and day care		JOURNAL OF PEDIATRICS		DOUBLE-BLIND; FOOD; CHILDREN; ANAPHYLAXIS; LIFE	Objective: Severe food-allergic reactions occur in schools, but. the features have not been described. Study design: Participants in the US Peanut and Tree Nut Allergy Registry (PAR) who indicated that their child experienced an allergic reaction in school or day care were randomly selected for a telephone interview conducted with a structured questionnaire. Results: Of 4586 participants in the PAR, 750 (16%) indicated a reaction in school or day care, and 100 subjects or parental surrogates described 124 reactions to peanut (115) or tree nuts (9); 64% of the reactions occurred in day care or preschool, and the remainder in elementary school or higher grades. Reactions were reported from ingestion (60%), skin contact/possible ingestion (24%), and inhalation/possible skin contact or ingestion (16%). In the majority of reactions caused by inhalation, concomitant ingestion/skin contact could not be ruled out. Various foods caused by ingestion, but peanut butter crab projects were commonly responsible for the skin contact (44%) or inhalation (41%) reactions. For 90% of reactions, medications were given (86% antihistamines, 28% epinephrine). Epinephrine was given in school by teachers in 4 cases, nurses in 7, and parents or others in the remainder. Treatment delays were attributed to delayed recognition of reactions, calling parents, not following emergency plans, and an unsuccessful attempt to administer epinephrine. Conclusions: School personnel must be educated to recognize and treat food-allergic reactions. Awareness must be increased to avoid accidental exposures, including exposure from peanut butter craft projects.	22	92	2001	6	10.1067/mpd.2001.111821	Pediatrics
Development of seasonal allergic rhinitis during the first 7 years of life. Background: Against the background of the controversial discussion about an increase in allergic rhinitis in recent years, intraindividual longitudinal data is lacking for IgE-mediated seasonal allergic rhinitis (SAR), Little is known about the development of SAR in terms of prevalence and incidence rates from birth to school age. Objective: In a prospective birth cohort, we investigated the development of sensitization and symptoms of SAR. SAR should be defined with high specificity, and associated risk factors should be determined. Methods: Annual longitudinal data about seasonal allergic symptoms and sensitization was available for 587 children from birth to their seventh birthday The definition of SAR was based on a combination of exposure-related symptoms and sensitization. Results: Up to 7 years of age, SAR developed in 15% of the children. Incidence and prevalence of symptoms and sensitization were low during early childhood (<2%) and increased steadily with age. Children in which SAR had already developed in the second year all were born in spring or early summer, resulting in at least two seasons of pollen exposure before manifestation of SAR. Risk factors assessed by multiple logistic regression analysis were male sex (odds ratio [OR] = 2.4), atopic mothers (OR = 2.6) and fathers (OR = 3.6) having allergic rhinitis themselves, first-born child (OR = 2.0), early sensitization to food (OR = 3.3), and atopic dermatitis (OR = 2.5), whereas early wheezing was not associated with SAR. Conclusion: The development of SAR is characterized by a marked increase in prevalence and incidence after the second year of life. Our longitudinal data further indicate that in combination with the risk of allergic predisposition, at least 2 seasons of pollen allergen exposure are needed before allergic rhinitis becomes clinically manifest.. seasonal allergic rhinitis| allergic sensitization| atopic family history| children|school-children| east-germany| late-onset| prevalence| asthma| sensitization| atopy| risk| isaac| adolescents.	NOV-2000	seasonal allergic rhinitis| allergic sensitization| atopic family history| children|school-children| east-germany| late-onset| prevalence| asthma| sensitization| atopy| risk| isaac| adolescents	Kulig, M; Klettke, U; Wahn, V; Forster, J; Bauer, CP; Wahn, U	Development of seasonal allergic rhinitis during the first 7 years of life		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	seasonal allergic rhinitis; allergic sensitization; atopic family history; children	SCHOOL-CHILDREN; EAST-GERMANY; LATE-ONSET; PREVALENCE; ASTHMA; SENSITIZATION; ATOPY; RISK; ISAAC; ADOLESCENTS	Background: Against the background of the controversial discussion about an increase in allergic rhinitis in recent years, intraindividual longitudinal data is lacking for IgE-mediated seasonal allergic rhinitis (SAR), Little is known about the development of SAR in terms of prevalence and incidence rates from birth to school age. Objective: In a prospective birth cohort, we investigated the development of sensitization and symptoms of SAR. SAR should be defined with high specificity, and associated risk factors should be determined. Methods: Annual longitudinal data about seasonal allergic symptoms and sensitization was available for 587 children from birth to their seventh birthday The definition of SAR was based on a combination of exposure-related symptoms and sensitization. Results: Up to 7 years of age, SAR developed in 15% of the children. Incidence and prevalence of symptoms and sensitization were low during early childhood (<2%) and increased steadily with age. Children in which SAR had already developed in the second year all were born in spring or early summer, resulting in at least two seasons of pollen exposure before manifestation of SAR. Risk factors assessed by multiple logistic regression analysis were male sex (odds ratio [OR] = 2.4), atopic mothers (OR = 2.6) and fathers (OR = 3.6) having allergic rhinitis themselves, first-born child (OR = 2.0), early sensitization to food (OR = 3.3), and atopic dermatitis (OR = 2.5), whereas early wheezing was not associated with SAR. Conclusion: The development of SAR is characterized by a marked increase in prevalence and incidence after the second year of life. Our longitudinal data further indicate that in combination with the risk of allergic predisposition, at least 2 seasons of pollen allergen exposure are needed before allergic rhinitis becomes clinically manifest.	26	92	2000	8	10.1067/mai.2000.110098	Allergy; Immunology
The effect of repeated ozone exposures on inflammatory markers in bronchoalveolar lavage fluid and mucosal biopsies. The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV1, an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.. airway inflammation| nitrogen-dioxide| humans| lung| responses| allergen| responsiveness| adaptation| pollution| fibrosis.	JUN-2000	airway inflammation| nitrogen-dioxide| humans| lung| responses| allergen| responsiveness| adaptation| pollution| fibrosis	Jorres, RA; Holz, O; Zachgo, W; Timm, P; Koschyk, S; Muller, B; Grimminger, F; Seeger, W; Kelly, FJ; Dunster, C; Frischer, T; Lubec, G; Waschewski, M; Niendorf, A; Magnussen, H	The effect of repeated ozone exposures on inflammatory markers in bronchoalveolar lavage fluid and mucosal biopsies		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		AIRWAY INFLAMMATION; NITROGEN-DIOXIDE; HUMANS; LUNG; RESPONSES; ALLERGEN; RESPONSIVENESS; ADAPTATION; POLLUTION; FIBROSIS	The aim of this study was to investigate the cellular and biochemical events associated with repeated exposures to ozone. Twenty-three healthy subjects underwent single exposures to 200 ppb ozone and to filtered air (FA), as well as repeated exposures to 200 ppb ozone on 4 consecutive days, each for 4 h of intermittent exercise. Bronchoalveolar lavage was performed and mucosal biopsies were taken 20 h after the single or the last of the repeated exposures. As compared with FA, the single exposure to ozone caused a decrease in FEV1, an increase in the percentages of neutrophils and lymphocytes, the concentrations of total protein, IL-6, IL-8, reduced glutathione, urate, and ortho-tyrosine in BAL fluid (BALF), but no changes in the cellular composition of biopsy. After the repeated exposure, the effect on lung function was abolished and differential cell counts in BALF were not significantly different from those after FA. However, the concentrations of total protein, IL-6, IL-8, reduced glutathione, and ortho-tyrosine were still increased. IL-10 could only be detected in BALF after repeated ozone exposures. Furthermore, macroscopic scores for bronchitis, erythema, and hypervulnerability of airway mucosa were increased, as well as numbers of neutrophils in bronchial mucosal biopsies. Our data demonstrate that airway inflammation persists after repeated ozone exposure, despite attenuation of some inflammatory markers in BALF and adaptation of lung function.	29	92	2000	7		General & Internal Medicine; Respiratory System
The Science of Early Life Toxic Stress for Pediatric Practice and Advocacy. Young children who experience toxic stress are at high risk for a number of health outcomes in adulthood, including cardiovascular disease, cancers, asthma, and depression. The American Academy of Pediatrics has recently called on pediatricians, informed by research from molecular biology, genomics, immunology, and neuroscience, to become leaders in science-based strategies to build strong foundations for children's life-long health. In this report, we provide an overview of the science of toxic stress. We summarize the development of the neuroendocrine-immune network, how its function is altered by early life adversity, and how these alterations then increase vulnerability to disease. The fact that early environments shape and calibrate the functioning of biological systems very early in life is both a cautionary tale about overlooking critical periods in development and reason for optimism about the promise of intervention. Even in the most extreme cases of adversity, well-timed changes to children's environments can improve outcomes. Pediatricians are in a unique position to contribute to the public discourse on health and social welfare by explaining how factors that seem distal to child health may be the key to some of the most intractable public health problems of our generation. We consider the challenges and opportunities for preventing toxic stress in the context of contemporary pediatric practice. Pediatrics 2013;131:319-327. toxic stress| health disparities| social determinants of health|childhood socioeconomic-status| inner-city cohort| immune-system| maternal-care| early experience| social-environment| metabolic syndrome| indoor allergens| cortisol-levels| children.	FEB-2013	toxic stress| health disparities| social determinants of health|childhood socioeconomic-status| inner-city cohort| immune-system| maternal-care| early experience| social-environment| metabolic syndrome| indoor allergens| cortisol-levels| children	Johnson, SB; Riley, AW; Granger, DA; Riis, J	The Science of Early Life Toxic Stress for Pediatric Practice and Advocacy		PEDIATRICS	toxic stress; health disparities; social determinants of health	CHILDHOOD SOCIOECONOMIC-STATUS; INNER-CITY COHORT; IMMUNE-SYSTEM; MATERNAL-CARE; EARLY EXPERIENCE; SOCIAL-ENVIRONMENT; METABOLIC SYNDROME; INDOOR ALLERGENS; CORTISOL-LEVELS; CHILDREN	Young children who experience toxic stress are at high risk for a number of health outcomes in adulthood, including cardiovascular disease, cancers, asthma, and depression. The American Academy of Pediatrics has recently called on pediatricians, informed by research from molecular biology, genomics, immunology, and neuroscience, to become leaders in science-based strategies to build strong foundations for children's life-long health. In this report, we provide an overview of the science of toxic stress. We summarize the development of the neuroendocrine-immune network, how its function is altered by early life adversity, and how these alterations then increase vulnerability to disease. The fact that early environments shape and calibrate the functioning of biological systems very early in life is both a cautionary tale about overlooking critical periods in development and reason for optimism about the promise of intervention. Even in the most extreme cases of adversity, well-timed changes to children's environments can improve outcomes. Pediatricians are in a unique position to contribute to the public discourse on health and social welfare by explaining how factors that seem distal to child health may be the key to some of the most intractable public health problems of our generation. We consider the challenges and opportunities for preventing toxic stress in the context of contemporary pediatric practice. Pediatrics 2013;131:319-327	82	91	2013	9	10.1542/peds.2012-0469	Pediatrics
T cell homing to epithelial barriers in allergic disease. Allergic inflammation develops in tissues that have large epithelial surface areas that are exposed to the environment, such as the lung, skin and gut. In the steady state, antigen-experienced memory T cells patrol these peripheral tissues to facilitate swift immune responses against invading pathogens. In at least two allergy-prone organs, the skin and the gut, memory T cells are programmed during the initial antigen priming to express trafficking receptors that enable them to preferentially home to these organs. In this review we propose that tissue-specific memory and inflammation-specific T cell trafficking facilitates the development of allergic disease in these organs. We thus review recent advances in our understanding of tissue-specific T cell trafficking and how regulation of T cell trafficking by the chemokine system contributes to allergic inflammation in mouse models and in human allergic diseases of the skin, lung and gut. Inflammation-and tissue-specific T lymphocyte trafficking pathways are currently being targeted as new treatments for non-allergic inflammatory diseases and may yield effective new therapeutics for allergic diseases.. cutaneous lymphocyte antigen| chemokine receptors ccr4| activation-regulated chemokine| smooth-muscle-cells| atopic-dermatitis| dendritic cells| retinoic-acid| t(h)2 cells| mouse model| th2 cells.	MAY-2012	cutaneous lymphocyte antigen| chemokine receptors ccr4| activation-regulated chemokine| smooth-muscle-cells| atopic-dermatitis| dendritic cells| retinoic-acid| t(h)2 cells| mouse model| th2 cells	Islam, SA; Luster, AD	T cell homing to epithelial barriers in allergic disease		NATURE MEDICINE		CUTANEOUS LYMPHOCYTE ANTIGEN; CHEMOKINE RECEPTORS CCR4; ACTIVATION-REGULATED CHEMOKINE; SMOOTH-MUSCLE-CELLS; ATOPIC-DERMATITIS; DENDRITIC CELLS; RETINOIC-ACID; T(H)2 CELLS; MOUSE MODEL; TH2 CELLS	Allergic inflammation develops in tissues that have large epithelial surface areas that are exposed to the environment, such as the lung, skin and gut. In the steady state, antigen-experienced memory T cells patrol these peripheral tissues to facilitate swift immune responses against invading pathogens. In at least two allergy-prone organs, the skin and the gut, memory T cells are programmed during the initial antigen priming to express trafficking receptors that enable them to preferentially home to these organs. In this review we propose that tissue-specific memory and inflammation-specific T cell trafficking facilitates the development of allergic disease in these organs. We thus review recent advances in our understanding of tissue-specific T cell trafficking and how regulation of T cell trafficking by the chemokine system contributes to allergic inflammation in mouse models and in human allergic diseases of the skin, lung and gut. Inflammation-and tissue-specific T lymphocyte trafficking pathways are currently being targeted as new treatments for non-allergic inflammatory diseases and may yield effective new therapeutics for allergic diseases.	167	91	2012	11	10.1038/nm.2760	Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine
Prenatal or Early-Life Exposure to Antibiotics and Risk of Childhood Asthma: A Systematic Review. CONTEXT: The increasing prevalence of childhood asthma has been associated with low microbial exposure as described by the hygiene hypothesis. OBJECTIVE: We sought to evaluate the evidence of association between antibiotic exposure during pregnancy or in the first year of life and risk of childhood asthma. METHODS: PubMed was systematically searched for studies published between 1950 and July 1, 2010. Those that assessed associations between antibiotic exposure during pregnancy or in the first year of life and asthma at ages 0 to 18 years (for pregnancy exposures) or ages 3 to 18 years (for first-year-of-life exposures) were included. Validity was assessed according to study design, age at asthma diagnosis, adjustment for respiratory infections, and consultation rates. RESULTS: For exposure in the first year of life, the pooled odds ratio (OR) for all studies (N = 20) was 1.52 (95% confidence interval [CI]: 1.30-1.77). Retrospective studies had the highest pooled risk estimate for asthma (OR: 2.04 [95% CI: 1.83-2.27]; n = 8) compared with database and prospective studies (OR: 1.25 [95% CI: 1.08-1.45]; n = 12). Risk estimates for studies that adjusted for respiratory infections (pooled OR: 1.16 [95% CI: 1.08-1.25]; n = 5) or later asthma onset (pooled OR for asthma at or after 2 years: OR: 1.16 [95% CI: 1.06-1.25]; n = 3) were weaker but remained significant. For exposure during pregnancy (n = 3 studies), the pooled OR was 1.24 (95% CI: 1.02-1.50). CONCLUSIONS: Antibiotics seem to slightly increase the risk of childhood asthma. Reverse causality and protopathic bias seem to be possible confounders for this relationship. Pediatrics 2011;127:1125-1138. antibiotics| asthma| meta-analysis| systematic review|birth cohort| allergic disease| 1st year| respiratory illness| airway inflammation| school-age| children| eczema| infections| prevalence.	JUN-2011	antibiotics| asthma| meta-analysis| systematic review|birth cohort| allergic disease| 1st year| respiratory illness| airway inflammation| school-age| children| eczema| infections| prevalence	Murk, W; Risnes, KR; Bracken, MB	Prenatal or Early-Life Exposure to Antibiotics and Risk of Childhood Asthma: A Systematic Review		PEDIATRICS	antibiotics; asthma; meta-analysis; systematic review	BIRTH COHORT; ALLERGIC DISEASE; 1ST YEAR; RESPIRATORY ILLNESS; AIRWAY INFLAMMATION; SCHOOL-AGE; CHILDREN; ECZEMA; INFECTIONS; PREVALENCE	CONTEXT: The increasing prevalence of childhood asthma has been associated with low microbial exposure as described by the hygiene hypothesis. OBJECTIVE: We sought to evaluate the evidence of association between antibiotic exposure during pregnancy or in the first year of life and risk of childhood asthma. METHODS: PubMed was systematically searched for studies published between 1950 and July 1, 2010. Those that assessed associations between antibiotic exposure during pregnancy or in the first year of life and asthma at ages 0 to 18 years (for pregnancy exposures) or ages 3 to 18 years (for first-year-of-life exposures) were included. Validity was assessed according to study design, age at asthma diagnosis, adjustment for respiratory infections, and consultation rates. RESULTS: For exposure in the first year of life, the pooled odds ratio (OR) for all studies (N = 20) was 1.52 (95% confidence interval [CI]: 1.30-1.77). Retrospective studies had the highest pooled risk estimate for asthma (OR: 2.04 [95% CI: 1.83-2.27]; n = 8) compared with database and prospective studies (OR: 1.25 [95% CI: 1.08-1.45]; n = 12). Risk estimates for studies that adjusted for respiratory infections (pooled OR: 1.16 [95% CI: 1.08-1.25]; n = 5) or later asthma onset (pooled OR for asthma at or after 2 years: OR: 1.16 [95% CI: 1.06-1.25]; n = 3) were weaker but remained significant. For exposure during pregnancy (n = 3 studies), the pooled OR was 1.24 (95% CI: 1.02-1.50). CONCLUSIONS: Antibiotics seem to slightly increase the risk of childhood asthma. Reverse causality and protopathic bias seem to be possible confounders for this relationship. Pediatrics 2011;127:1125-1138	54	91	2011	14	10.1542/peds.2010-2092	Pediatrics
Interactions between helminth parasites and allergy. Purpose of review To review the findings of recent human studies of the association between helminth parasite infections and allergy and discuss their potential relevance to public health. Recent findings Different helminth parasites may have different effects on allergy that may depend on the timing or intensity of the exposure or host genetic factors. Infections with Trichuris trichiura in early life are associated with a reduced prevalence of allergen skin test reactivity later in life and infants of helminth-infected mothers have been reported to have a reduced prevalence of eczema. Hookworm infection has been associated with a reduced prevalence of asthma in Ethiopia. Several studies have reported that anti-Ascaris IgE is an important risk factor for asthma, but this could be explained by an enhanced ability of atopics to produce IgE. Toxocara infections may be associated with an increased risk of wheeze in some populations that may be caused by the host response to the parasite or by parasite-enhanced Th2 responses to aeroallergens. Summary Although helminth infections can modulate the host inflammatory response directed against the parasite, a causal association between helminths and atopic diseases remains uncertain.. allergy| asthma| geohelminths| helminths|skin-test reactivity| ascaris-immunoglobulin-e| south-african children| induced interleukin-10| risk-factors| rural area| gabonese schoolchildren| geohelminth infections| anthelmintic treatment| atopic sensitization.	FEB-2009	allergy| asthma| geohelminths| helminths|skin-test reactivity| ascaris-immunoglobulin-e| south-african children| induced interleukin-10| risk-factors| rural area| gabonese schoolchildren| geohelminth infections| anthelmintic treatment| atopic sensitization	Cooper, PJ	Interactions between helminth parasites and allergy		CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY	allergy; asthma; geohelminths; helminths	SKIN-TEST REACTIVITY; ASCARIS-IMMUNOGLOBULIN-E; SOUTH-AFRICAN CHILDREN; INDUCED INTERLEUKIN-10; RISK-FACTORS; RURAL AREA; GABONESE SCHOOLCHILDREN; GEOHELMINTH INFECTIONS; ANTHELMINTIC TREATMENT; ATOPIC SENSITIZATION	Purpose of review To review the findings of recent human studies of the association between helminth parasite infections and allergy and discuss their potential relevance to public health. Recent findings Different helminth parasites may have different effects on allergy that may depend on the timing or intensity of the exposure or host genetic factors. Infections with Trichuris trichiura in early life are associated with a reduced prevalence of allergen skin test reactivity later in life and infants of helminth-infected mothers have been reported to have a reduced prevalence of eczema. Hookworm infection has been associated with a reduced prevalence of asthma in Ethiopia. Several studies have reported that anti-Ascaris IgE is an important risk factor for asthma, but this could be explained by an enhanced ability of atopics to produce IgE. Toxocara infections may be associated with an increased risk of wheeze in some populations that may be caused by the host response to the parasite or by parasite-enhanced Th2 responses to aeroallergens. Summary Although helminth infections can modulate the host inflammatory response directed against the parasite, a causal association between helminths and atopic diseases remains uncertain.	70	91	2009	9	10.1097/ACI.0b013e32831f44a6	Allergy; Immunology
Do helminth parasites protect against atopy and allergic disease?. Allergic diseases are rare in areas with high helminth parasite exposure and common where helminth exposure is lacking or significantly reduced, such as urban areas of developing countries and industrialized nations. Studies suggest that helminths induce a systemic immuno-modulatory network, including regulatory T cells and anti-inflammatory IL-10, which might play a key role in the protection against the allergic phenotype. Here, we review the current cross-sectional, birth cohort, and intervention study evidence for a protective effect of helminth infection on allergy. There is increasing evidence for a causal relationship between helminth infection and reduced skin prick test responsiveness to allergens. Cross-sectional studies have shown a consistent negative relationship, and these results have been confirmed in several, although not all, intervention studies. The immunological basis for this protective effect is less clear. Recent studies do not support the mast-cell IgE saturation hypothesis, but suggest that protection is associated with IL-10 production. As for allergic disease, cross-sectional studies support a negative relationship between clinical asthma and infection with some helminth species, particularly hookworm, but more studies are required to draw conclusions for eczema and rhinitis. In addition, none of the few intervention studies to date have demonstrated an increase in clinical allergy after helminth treatment, and further studies are needed. Furthermore, we are only beginning to understand the host genetic factors that are potentially involved. A genetically predetermined T-helper type 2 cell-dominated cytokine milieu reduces parasite burden and may enhance host survival in an environment where helminth parasites are prevalent. Lack of parasite exposure in such hosts might lead to hypersensitivity to seemingly minor environmental allergen stimuli. Large birth cohort studies in helminth-endemic areas that use epidemiological, genetic, and immunological tools are required to further examine how helminth parasites affect the development of atopy and allergic disease. Intervention studies with hookworm in parasite-naive allergic individuals are currently ongoing in the United Kingdom to test the above hypotheses further.. schistosoma-mansoni infection| necator-americanus infection| skin-test reactivity| ige antibody-levels| house-dust mite| ascaris-lumbricoides| rural area| gabonese schoolchildren| induced interleukin-10| intestinal parasites.	JAN-2009	schistosoma-mansoni infection| necator-americanus infection| skin-test reactivity| ige antibody-levels| house-dust mite| ascaris-lumbricoides| rural area| gabonese schoolchildren| induced interleukin-10| intestinal parasites	Flohr, C; Quinnell, RJ; Britton, J	Do helminth parasites protect against atopy and allergic disease?		CLINICAL AND EXPERIMENTAL ALLERGY		SCHISTOSOMA-MANSONI INFECTION; NECATOR-AMERICANUS INFECTION; SKIN-TEST REACTIVITY; IGE ANTIBODY-LEVELS; HOUSE-DUST MITE; ASCARIS-LUMBRICOIDES; RURAL AREA; GABONESE SCHOOLCHILDREN; INDUCED INTERLEUKIN-10; INTESTINAL PARASITES	Allergic diseases are rare in areas with high helminth parasite exposure and common where helminth exposure is lacking or significantly reduced, such as urban areas of developing countries and industrialized nations. Studies suggest that helminths induce a systemic immuno-modulatory network, including regulatory T cells and anti-inflammatory IL-10, which might play a key role in the protection against the allergic phenotype. Here, we review the current cross-sectional, birth cohort, and intervention study evidence for a protective effect of helminth infection on allergy. There is increasing evidence for a causal relationship between helminth infection and reduced skin prick test responsiveness to allergens. Cross-sectional studies have shown a consistent negative relationship, and these results have been confirmed in several, although not all, intervention studies. The immunological basis for this protective effect is less clear. Recent studies do not support the mast-cell IgE saturation hypothesis, but suggest that protection is associated with IL-10 production. As for allergic disease, cross-sectional studies support a negative relationship between clinical asthma and infection with some helminth species, particularly hookworm, but more studies are required to draw conclusions for eczema and rhinitis. In addition, none of the few intervention studies to date have demonstrated an increase in clinical allergy after helminth treatment, and further studies are needed. Furthermore, we are only beginning to understand the host genetic factors that are potentially involved. A genetically predetermined T-helper type 2 cell-dominated cytokine milieu reduces parasite burden and may enhance host survival in an environment where helminth parasites are prevalent. Lack of parasite exposure in such hosts might lead to hypersensitivity to seemingly minor environmental allergen stimuli. Large birth cohort studies in helminth-endemic areas that use epidemiological, genetic, and immunological tools are required to further examine how helminth parasites affect the development of atopy and allergic disease. Intervention studies with hookworm in parasite-naive allergic individuals are currently ongoing in the United Kingdom to test the above hypotheses further.	114	91	2009	13	10.1111/j.1365-2222.2008.03134.x	Allergy; Immunology
Acute respiratory health effects of air pollution on children with asthma in US inner cities. Background: Children with asthma in inner-city communities may be particularly vulnerable to adverse effects of air pollution because of their airways disease and exposure to relatively high levels of motor vehicle emissions. Objective: To investigate the association between fluctuations in outdoor air pollution and asthma morbidity among inner-city children with asthma. Methods: We analyzed data from 861 children with persistent asthma in 7 US urban communities who performed 2-week periods of twice-daily pulmonary function testing every 6 months for 2 years. Asthma symptom data were collected every 2 months. Daily pollution measurements were obtained from the Aerometric Information Retrieval System. The relationship of lung function and symptoms to fluctuations in pollutant concentrations was examined by using mixed models. Results: Almost all pollutant concentrations measured were below the National Ambient Air Quality Standards. In single-pollutant models, higher 5-day average concentrations of NO(2), sulfur dioxide, and particles smaller than 2.5 mu m were associated with significantly lower pulmonary function. Higher pollutant levels were independently associated with reduced lung function in a 3-pollutant model. Higher concentrations of NO(2) and particles smaller than 2.5 mu m were associated with asthma-related missed school days, and higher NO(2) concentrations were associated with asthma symptoms. Conclusion: Among inner-city children with asthma, short-term increases in air pollutant concentrations below the National Ambient Air Quality Standards were associated with adverse respiratory health effects. The associations with NO(2) suggest that motor vehicle emissions may be causing excess morbidity in this population.. nitrogen dioxide| ozone| sulfur dioxide| carbon monoxide| fine particle emissions| asthma in children|peak expiratory flow| fine particles| daily mortality| environmental intervention| hospital admissions| childhood asthma| symptom severity| medication use| mexico-city| urban air.	MAY-2008	nitrogen dioxide| ozone| sulfur dioxide| carbon monoxide| fine particle emissions| asthma in children|peak expiratory flow| fine particles| daily mortality| environmental intervention| hospital admissions| childhood asthma| symptom severity| medication use| mexico-city| urban air	O'Connor, GT; Neas, L; Vaughn, B; Kattan, M; Mitchell, H; Crain, EF; Evans, R; Gruchalla, R; Morgan, W; Stout, J; Adams, GK; Lippmann, M	Acute respiratory health effects of air pollution on children with asthma in US inner cities		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	nitrogen dioxide; ozone; sulfur dioxide; carbon monoxide; fine particle emissions; asthma in children	PEAK EXPIRATORY FLOW; FINE PARTICLES; DAILY MORTALITY; ENVIRONMENTAL INTERVENTION; HOSPITAL ADMISSIONS; CHILDHOOD ASTHMA; SYMPTOM SEVERITY; MEDICATION USE; MEXICO-CITY; URBAN AIR	Background: Children with asthma in inner-city communities may be particularly vulnerable to adverse effects of air pollution because of their airways disease and exposure to relatively high levels of motor vehicle emissions. Objective: To investigate the association between fluctuations in outdoor air pollution and asthma morbidity among inner-city children with asthma. Methods: We analyzed data from 861 children with persistent asthma in 7 US urban communities who performed 2-week periods of twice-daily pulmonary function testing every 6 months for 2 years. Asthma symptom data were collected every 2 months. Daily pollution measurements were obtained from the Aerometric Information Retrieval System. The relationship of lung function and symptoms to fluctuations in pollutant concentrations was examined by using mixed models. Results: Almost all pollutant concentrations measured were below the National Ambient Air Quality Standards. In single-pollutant models, higher 5-day average concentrations of NO(2), sulfur dioxide, and particles smaller than 2.5 mu m were associated with significantly lower pulmonary function. Higher pollutant levels were independently associated with reduced lung function in a 3-pollutant model. Higher concentrations of NO(2) and particles smaller than 2.5 mu m were associated with asthma-related missed school days, and higher NO(2) concentrations were associated with asthma symptoms. Conclusion: Among inner-city children with asthma, short-term increases in air pollutant concentrations below the National Ambient Air Quality Standards were associated with adverse respiratory health effects. The associations with NO(2) suggest that motor vehicle emissions may be causing excess morbidity in this population.	44	91	2008	7	10.1016/j.jaci.2008.02.020	Allergy; Immunology
"Skin exposure to isocyanates: Reasons for concern. OBJECTIVE: Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma. DATA SOURCES: We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma. DATA EXTRACTION: We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords ""isocyanate,"" ""asthma,"" ""skin,"" ""sensitization,"" and other synonymous terms, and our own extensive collection of isocyanate publications. DATA SYNTHESIS: Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization. CONCLUSIONS: Integrated animal and human research is needed to better understand the role of skin exposure in human isocyanate asthma and to improve diagnosis and prevention. In spite of substantial research needs, sufficient evidence already exists to justify greater emphasis on the potential risks of isocyanate skin exposure and the importance of preventing such exposures at work and during consumer use of certain isocyanate products.. asthma| dermal exposure| isocyanates| sensitization| skin|allergic contact-dermatitis| methylene diphenyl diisocyanate| toluene diisocyanate| occupational asthma| polyurethane foam| body repair| in-vivo| 1,6-hexamethylene diisocyanate| trimellitic anhydride| respiratory allergy."	MAR-2007	asthma| dermal exposure| isocyanates| sensitization| skin|allergic contact-dermatitis| methylene diphenyl diisocyanate| toluene diisocyanate| occupational asthma| polyurethane foam| body repair| in-vivo| 1,6-hexamethylene diisocyanate| trimellitic anhydride| respiratory allergy	Bello, D; Herrick, CA; Smith, TJ; Woskie, SR; Streicher, RP; Cullen, MR; Liu, YC; Redlich, CA	Skin exposure to isocyanates: Reasons for concern		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; dermal exposure; isocyanates; sensitization; skin	ALLERGIC CONTACT-DERMATITIS; METHYLENE DIPHENYL DIISOCYANATE; TOLUENE DIISOCYANATE; OCCUPATIONAL ASTHMA; POLYURETHANE FOAM; BODY REPAIR; IN-VIVO; 1,6-HEXAMETHYLENE DIISOCYANATE; TRIMELLITIC ANHYDRIDE; RESPIRATORY ALLERGY	"OBJECTIVE: Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma. DATA SOURCES: We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma. DATA EXTRACTION: We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords ""isocyanate,"" ""asthma,"" ""skin,"" ""sensitization,"" and other synonymous terms, and our own extensive collection of isocyanate publications. DATA SYNTHESIS: Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization. CONCLUSIONS: Integrated animal and human research is needed to better understand the role of skin exposure in human isocyanate asthma and to improve diagnosis and prevention. In spite of substantial research needs, sufficient evidence already exists to justify greater emphasis on the potential risks of isocyanate skin exposure and the importance of preventing such exposures at work and during consumer use of certain isocyanate products."	94	91	2007	8	10.1289/ehp.9557	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Asthma and air pollution in the Bronx: Methodological and data considerations in using GIS for environmental justice and health research. This paper examines methods of environmental justice assessment with Geographic Information Systems, using research on the spatial correspondence between asthma and air pollution in the Bronx, New York City as a case study. Issues of spatial extent and resolution, the selection of environmental burdens to analyze, data and methodological limitations, and different approaches to delineating exposure are discussed in the context of the asthma study, which, through proximity analysis, found that people living near (within specified distance buffers) noxious land uses were up to 66 percent more likely to be hospitalized for asthma, and were 30 percent more likely to be poor and 13 percent more likely to be a minority than those outside the buffers. (c) 2005 Elsevier Ltd. All rights reserved.. asthma| air pollution| geographic information systems (gis)| environmental justice| environmental health| proximity analysis|geographic information-systems| disparities geocoding project| chronic respiratory symptoms| public-health| childhood asthma| children| equity| epidemiology| road| pollutants.	MAR-2007	asthma| air pollution| geographic information systems (gis)| environmental justice| environmental health| proximity analysis|geographic information-systems| disparities geocoding project| chronic respiratory symptoms| public-health| childhood asthma| children| equity| epidemiology| road| pollutants	Maantay, J	Asthma and air pollution in the Bronx: Methodological and data considerations in using GIS for environmental justice and health research		HEALTH & PLACE	asthma; air pollution; Geographic Information Systems (GIS); environmental justice; environmental health; proximity analysis	GEOGRAPHIC INFORMATION-SYSTEMS; DISPARITIES GEOCODING PROJECT; CHRONIC RESPIRATORY SYMPTOMS; PUBLIC-HEALTH; CHILDHOOD ASTHMA; CHILDREN; EQUITY; EPIDEMIOLOGY; ROAD; POLLUTANTS	This paper examines methods of environmental justice assessment with Geographic Information Systems, using research on the spatial correspondence between asthma and air pollution in the Bronx, New York City as a case study. Issues of spatial extent and resolution, the selection of environmental burdens to analyze, data and methodological limitations, and different approaches to delineating exposure are discussed in the context of the asthma study, which, through proximity analysis, found that people living near (within specified distance buffers) noxious land uses were up to 66 percent more likely to be hospitalized for asthma, and were 30 percent more likely to be poor and 13 percent more likely to be a minority than those outside the buffers. (c) 2005 Elsevier Ltd. All rights reserved.	100	91	2007	25	10.1016/j.healthplace.2005.09.009	Public, Environmental & Occupational Health
Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary report. Background: Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response. Interleukin 10 (IL-10) plays a crucial role in inducing allergen-specific tolerance; however, no previous studies have examined IL-10 production after sublingual immunotherapy (SLIT). Objective: To evaluate T-cell proliferation and IL-10 production in patients successfully treated with SLIT for house dust mites (HDMs). Methods: Peripheral blood mononuclear cells were isolated from patients after at least 3 years of successful HDM SLIT and from matched untreated allergic patients and healthy control subjects. After 3 and 6 days of in vitro stimulation with phytohemagglutinin (PHA), Candida albicans, and Dermatophagoides farinae, proliferation and production of IL-10 were measured. Results: Patients treated with SLIT showed a significant reduction of proliferation induced by C albicans compared with untreated atopic patients (P < .001), but a significant reduction was also demonstrated in healthy controls compared with untreated atopic patients (P < .001). Patients treated with SLIT also showed a significant increase of IL-10 production after Candida and PHA stimuli compared with patients with untreated rhinitis (P < .001 for both). Patients with untreated rhinitis did not produce IL-10. Conclusion: This preliminary study confirms reduced T-cell proliferation and preliminarily provides the first evidence, to our knowledge, of peripheral IL-10 production in allergic patients successfully treated with HDM SLIT.. regulatory t-cells| grass-pollen immunotherapy| clinical immunology| airway inflammation| cytokine production| allergic rhinitis| oral tolerance| il-10| suppression| disease.	JUL-2005	regulatory t-cells| grass-pollen immunotherapy| clinical immunology| airway inflammation| cytokine production| allergic rhinitis| oral tolerance| il-10| suppression| disease	Ciprandi, G; Fenoglio, D; Cirillo, I; Vizzaccaro, A; Ferrera, A; Tosca, MA; Puppo, F	Induction of interleukin 10 by sublingual immunotherapy for house dust mites: a preliminary report		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		REGULATORY T-CELLS; GRASS-POLLEN IMMUNOTHERAPY; CLINICAL IMMUNOLOGY; AIRWAY INFLAMMATION; CYTOKINE PRODUCTION; ALLERGIC RHINITIS; ORAL TOLERANCE; IL-10; SUPPRESSION; DISEASE	Background: Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response. Interleukin 10 (IL-10) plays a crucial role in inducing allergen-specific tolerance; however, no previous studies have examined IL-10 production after sublingual immunotherapy (SLIT). Objective: To evaluate T-cell proliferation and IL-10 production in patients successfully treated with SLIT for house dust mites (HDMs). Methods: Peripheral blood mononuclear cells were isolated from patients after at least 3 years of successful HDM SLIT and from matched untreated allergic patients and healthy control subjects. After 3 and 6 days of in vitro stimulation with phytohemagglutinin (PHA), Candida albicans, and Dermatophagoides farinae, proliferation and production of IL-10 were measured. Results: Patients treated with SLIT showed a significant reduction of proliferation induced by C albicans compared with untreated atopic patients (P < .001), but a significant reduction was also demonstrated in healthy controls compared with untreated atopic patients (P < .001). Patients treated with SLIT also showed a significant increase of IL-10 production after Candida and PHA stimuli compared with patients with untreated rhinitis (P < .001 for both). Patients with untreated rhinitis did not produce IL-10. Conclusion: This preliminary study confirms reduced T-cell proliferation and preliminarily provides the first evidence, to our knowledge, of peripheral IL-10 production in allergic patients successfully treated with HDM SLIT.	45	91	2005	7		Allergy; Immunology
Neutrophil elastase induces mucus cell metaplasia in mouse lung. Goblet cell hyperplasia in the superficial airway epithelia is a signature pathological feature of chronic bronchitis and cystic fibrosis. In these chronic inflammatory airway diseases, neutrophil elastase (NE) is found in high concentrations in the epithelial lining fluid. NE has been reported to trigger mucin secretion and increase mucin gene expression in vitro. We hypothesized that chronic NE exposure to murine airways in vivo would induce goblet cell metaplasia. Human NE (50 mug) or PBS saline was aspirated intratracheally by male Balb/c (6 wk of age) mice on days 1, 4, and 7. On days 8, 11, and 14, lung tissues for histology and bronchoalveolar lavage (BAL) samples for cell counts and cytokine levels were obtained. NE induced Muc5ac mRNA and protein expression and goblet cell metaplasia on days 8, 11, and 14. These cellular changes were the result of proteolytic activity, since the addition of an elastase inhibitor, methoxysuccinyl Ala-Ala-Pro-Val chloromethylketone (AAPV-CMK), blocked NE-induced Muc5ac expression and goblet cell metaplasia. NE significantly increased keratinocyte-derived chemokine and IL-5 in BAL and increased lung tissue inflammation and BAL leukocyte counts. The addition of AAPV-CMK reduced these measures of inflammation to control levels. These experiments suggest that NE proteolytic activity initiates an inflammatory process leading to goblet cell metaplasia.. neutrophil elastase| goblet cell metaplasia| muc5ac|airway epithelial-cells| factor receptor activation| induced muc5ac expression| rat bronchial epithelium| mucin gene-expression| gland serous cells| nasal epithelium| protein expression| messenger-rna| asthma.	DEC-2004	neutrophil elastase| goblet cell metaplasia| muc5ac|airway epithelial-cells| factor receptor activation| induced muc5ac expression| rat bronchial epithelium| mucin gene-expression| gland serous cells| nasal epithelium| protein expression| messenger-rna| asthma	Voynow, JA; Fischer, BM; Malarkey, DE; Burch, LH; Wong, T; Longphre, M; Ho, SB; Foster, WM	Neutrophil elastase induces mucus cell metaplasia in mouse lung		AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY	neutrophil elastase; goblet cell metaplasia; Muc5ac	AIRWAY EPITHELIAL-CELLS; FACTOR RECEPTOR ACTIVATION; INDUCED MUC5AC EXPRESSION; RAT BRONCHIAL EPITHELIUM; MUCIN GENE-EXPRESSION; GLAND SEROUS CELLS; NASAL EPITHELIUM; PROTEIN EXPRESSION; MESSENGER-RNA; ASTHMA	Goblet cell hyperplasia in the superficial airway epithelia is a signature pathological feature of chronic bronchitis and cystic fibrosis. In these chronic inflammatory airway diseases, neutrophil elastase (NE) is found in high concentrations in the epithelial lining fluid. NE has been reported to trigger mucin secretion and increase mucin gene expression in vitro. We hypothesized that chronic NE exposure to murine airways in vivo would induce goblet cell metaplasia. Human NE (50 mug) or PBS saline was aspirated intratracheally by male Balb/c (6 wk of age) mice on days 1, 4, and 7. On days 8, 11, and 14, lung tissues for histology and bronchoalveolar lavage (BAL) samples for cell counts and cytokine levels were obtained. NE induced Muc5ac mRNA and protein expression and goblet cell metaplasia on days 8, 11, and 14. These cellular changes were the result of proteolytic activity, since the addition of an elastase inhibitor, methoxysuccinyl Ala-Ala-Pro-Val chloromethylketone (AAPV-CMK), blocked NE-induced Muc5ac expression and goblet cell metaplasia. NE significantly increased keratinocyte-derived chemokine and IL-5 in BAL and increased lung tissue inflammation and BAL leukocyte counts. The addition of AAPV-CMK reduced these measures of inflammation to control levels. These experiments suggest that NE proteolytic activity initiates an inflammatory process leading to goblet cell metaplasia.	65	91	2004	10	10.1152/ajplung.00140.2004	Physiology; Respiratory System
The Copenhagen Prospective Study on Asthma in Childhood (COPSAC): design, rationale, and baseline data from a longitudinal birth cohort study. Background: The atopic diseases asthma, atopic dermatitis, and allergic rhinitis are the most common chronic diseases in children, and their prevalence has increased recently in industrialized nations. Little is known about the genetic-environmental interaction factors driving such proliferation. Objective: To investigate the relationships among genetic, environmental, and lifestyle factors in the development of atopic diseases in high-risk children with the aim of developing evidence-based prevention strategies. Methods: The Copenhagen Prospective Study on Asthma in Childhood is a single-center, birth cohort study of children of asthmatic mothers. Objective assessments begin at birth, with scheduled visits every 6 months and when acute symptoms manifest. Clinical outcomes comprise preasthma, asthma, atopic dermatitis, allergic rhinitis, allergy, lung function, and bronchial responsiveness. Exposure assessments comprise respiratory, intestinal, and skin microbiology; the child's diet; indoor and outdoor air quality; allergens; and indicators of lifestyle. Genetic characteristics of probands and parents are evaluated. Quality assurance follows Good Clinical Practice guidelines. Results: Four hundred eleven infants of asthmatic mothers were enrolled at the age of I month. The children were born between August 2, 1998, and December 28, 2001. Compared with the Copenhagen population, mothers of the cohort population were less likely to have given natural childbirth. The households were slightly less affluent, with fewer children and fewer pets. Whites may be overrepresented. At age 2 years, 93% of the infants were still actively participating in the cohort. Conclusions: This longitudinal birth cohort study of high-risk Danish infants consists of objective phenotyping, detailed information on exposure, high data quality, and a high participant retention rate.. respiratory syncytial virus| atopic-dermatitis| increasing prevalence| personal exposure| healthy-children| hay-fever| 1st year| age| population| symptoms.	OCT-2004	respiratory syncytial virus| atopic-dermatitis| increasing prevalence| personal exposure| healthy-children| hay-fever| 1st year| age| population| symptoms	Bisgaard, H	The Copenhagen Prospective Study on Asthma in Childhood (COPSAC): design, rationale, and baseline data from a longitudinal birth cohort study		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		RESPIRATORY SYNCYTIAL VIRUS; ATOPIC-DERMATITIS; INCREASING PREVALENCE; PERSONAL EXPOSURE; HEALTHY-CHILDREN; HAY-FEVER; 1ST YEAR; AGE; POPULATION; SYMPTOMS	Background: The atopic diseases asthma, atopic dermatitis, and allergic rhinitis are the most common chronic diseases in children, and their prevalence has increased recently in industrialized nations. Little is known about the genetic-environmental interaction factors driving such proliferation. Objective: To investigate the relationships among genetic, environmental, and lifestyle factors in the development of atopic diseases in high-risk children with the aim of developing evidence-based prevention strategies. Methods: The Copenhagen Prospective Study on Asthma in Childhood is a single-center, birth cohort study of children of asthmatic mothers. Objective assessments begin at birth, with scheduled visits every 6 months and when acute symptoms manifest. Clinical outcomes comprise preasthma, asthma, atopic dermatitis, allergic rhinitis, allergy, lung function, and bronchial responsiveness. Exposure assessments comprise respiratory, intestinal, and skin microbiology; the child's diet; indoor and outdoor air quality; allergens; and indicators of lifestyle. Genetic characteristics of probands and parents are evaluated. Quality assurance follows Good Clinical Practice guidelines. Results: Four hundred eleven infants of asthmatic mothers were enrolled at the age of I month. The children were born between August 2, 1998, and December 28, 2001. Compared with the Copenhagen population, mothers of the cohort population were less likely to have given natural childbirth. The households were slightly less affluent, with fewer children and fewer pets. Whites may be overrepresented. At age 2 years, 93% of the infants were still actively participating in the cohort. Conclusions: This longitudinal birth cohort study of high-risk Danish infants consists of objective phenotyping, detailed information on exposure, high data quality, and a high participant retention rate.	66	91	2004	9		Allergy; Immunology
Nordic Occupational Skin Questionnaire (NOSQ-2002): a new tool for surveying occupational skin diseases and exposure. Occupational skin diseases are among the most frequent work-related diseases in industrialized countries. Good occupational skin disease statistics exist in few countries. Questionnaire studies are needed to get more data on the epidemiology of occupational skin diseases. The Nordic Occupational Skin Questionnaire Group has developed a new questionnaire tool - Nordic Occupational Skin Questionnaire (NOSQ-2002) - for surveys on work-related skin disease and exposures to environmental factors. The 2 NOSQ-2002 questionnaires have been compiled by using existing questionnaires and experience. NOSQ-2002/SHORT is a ready-to-use 4-page questionnaire for screening and monitoring occupational skin diseases, e.g. in a population or workplace. All the questions in the short questionnaire (NOSQ-2002/SHORT) are included in the long version, NOSQ-2002/LONG, which contains a pool of questions to be chosen according to research needs and tailored to specific populations. The NOSQ-2002 report includes, in addition to the questionnaires, a comprehensive manual for researchers on planning and conducting a questionnaire survey on hand eczema and relevant exposures. NOSQ-2002 questionnaires have been compiled in English and translated into Danish, Swedish, Finnish and Icelandic. The use of NOSQ-2002 will benefit research on occupational skin diseases by providing more standardized data, which can be compared between studies and countries.. eczema| epidemiology| exposure| hand dermatitis| nosq-2002| occupational| questionnaire design| questionnaire methods| skin diseases|party diagnostic-criteria| reported hand eczema| allergic contact sensitization| atopic-dermatitis| danish population| glostrup allergy| prevalence| dermatoses| validation| netherlands.	AUG-2003	eczema| epidemiology| exposure| hand dermatitis| nosq-2002| occupational| questionnaire design| questionnaire methods| skin diseases|party diagnostic-criteria| reported hand eczema| allergic contact sensitization| atopic-dermatitis| danish population| glostrup allergy| prevalence| dermatoses| validation| netherlands	Susitaival, P; Flyvholm, MA; Meding, B; Kanerva, L; Lindberg, M; Svensson, A; Olafsson, JH	Nordic Occupational Skin Questionnaire (NOSQ-2002): a new tool for surveying occupational skin diseases and exposure		CONTACT DERMATITIS	eczema; epidemiology; exposure; hand dermatitis; NOSQ-2002; occupational; questionnaire design; questionnaire methods; skin diseases	PARTY DIAGNOSTIC-CRITERIA; REPORTED HAND ECZEMA; ALLERGIC CONTACT SENSITIZATION; ATOPIC-DERMATITIS; DANISH POPULATION; GLOSTRUP ALLERGY; PREVALENCE; DERMATOSES; VALIDATION; NETHERLANDS	Occupational skin diseases are among the most frequent work-related diseases in industrialized countries. Good occupational skin disease statistics exist in few countries. Questionnaire studies are needed to get more data on the epidemiology of occupational skin diseases. The Nordic Occupational Skin Questionnaire Group has developed a new questionnaire tool - Nordic Occupational Skin Questionnaire (NOSQ-2002) - for surveys on work-related skin disease and exposures to environmental factors. The 2 NOSQ-2002 questionnaires have been compiled by using existing questionnaires and experience. NOSQ-2002/SHORT is a ready-to-use 4-page questionnaire for screening and monitoring occupational skin diseases, e.g. in a population or workplace. All the questions in the short questionnaire (NOSQ-2002/SHORT) are included in the long version, NOSQ-2002/LONG, which contains a pool of questions to be chosen according to research needs and tailored to specific populations. The NOSQ-2002 report includes, in addition to the questionnaires, a comprehensive manual for researchers on planning and conducting a questionnaire survey on hand eczema and relevant exposures. NOSQ-2002 questionnaires have been compiled in English and translated into Danish, Swedish, Finnish and Icelandic. The use of NOSQ-2002 will benefit research on occupational skin diseases by providing more standardized data, which can be compared between studies and countries.	46	91	2003	7	10.1111/j.0105-1873.2003.00159.x	Allergy; Dermatology
"The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. The aim of the present study was to determine the effect of treatment with omalizumab, an anti-immunoglobulin E antibody, on asthma-related quality of life (AQoL) in patients with moderate-to-severe allergic asthma. A total of 546 patients with allergic asthma were randomised to double-blind subcutaneous treatment with either placebo or omalizumab for 52 weeks. A constant beclomethasone dipropionate dose was maintained during the first 16 weeks (steroid-stable phase). This was followed by a 12-week steroid-reduction phase. The core study was followed by a 24-week double-blind extension phase. AQoL was evaluated at baseline and at the end of the steroid-stable (week 16), steroid-reduction (week 28) and extension phases (week 52) using the Juniper Asthma Quality of Life Questionnaire (AQLQ). Baseline AQLQ scores were comparable for the two treatment groups. Relative to placebo, omalizumab-treated patients demonstrated statistically significant improvements from baseline across all four AQLQ domains, as well as overall AQoL score, at weeks 16 (except environmental exposure), 28 and 52. Patients on omalizumab were also more likely to achieve clinically significant improvements in AQoL during the course of the study. Overall, almost 70% of patients and investigators rated treatment with omalizumab as ""excellent/good"", compared with similar to40% of placebo recipients. Clinical studies show that omalizumab enhances disease control whilst reducing corticosteroid consumption in patients with allergic asthma. The results of the present study show that these changes are paralleled by improvements in asthma-related quality of life that are meaningful to such patients.. allergic asthma| anti-immunoglobulin e| omalizumab| quality of life|of-life| airway hyperresponsiveness| clinical-trials| disease| questionnaire| inflammation| inhibition| severity| therapy."	NOV-2002	allergic asthma| anti-immunoglobulin e| omalizumab| quality of life|of-life| airway hyperresponsiveness| clinical-trials| disease| questionnaire| inflammation| inhibition| severity| therapy	Buhl, R; Hanf, G; Soler, M; Bensch, G; Wolfe, J; Everhard, F; Champain, K; Fox, H; Thirlwell, J	The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma		EUROPEAN RESPIRATORY JOURNAL	allergic asthma; anti-immunoglobulin E; omalizumab; quality of life	OF-LIFE; AIRWAY HYPERRESPONSIVENESS; CLINICAL-TRIALS; DISEASE; QUESTIONNAIRE; INFLAMMATION; INHIBITION; SEVERITY; THERAPY	"The aim of the present study was to determine the effect of treatment with omalizumab, an anti-immunoglobulin E antibody, on asthma-related quality of life (AQoL) in patients with moderate-to-severe allergic asthma. A total of 546 patients with allergic asthma were randomised to double-blind subcutaneous treatment with either placebo or omalizumab for 52 weeks. A constant beclomethasone dipropionate dose was maintained during the first 16 weeks (steroid-stable phase). This was followed by a 12-week steroid-reduction phase. The core study was followed by a 24-week double-blind extension phase. AQoL was evaluated at baseline and at the end of the steroid-stable (week 16), steroid-reduction (week 28) and extension phases (week 52) using the Juniper Asthma Quality of Life Questionnaire (AQLQ). Baseline AQLQ scores were comparable for the two treatment groups. Relative to placebo, omalizumab-treated patients demonstrated statistically significant improvements from baseline across all four AQLQ domains, as well as overall AQoL score, at weeks 16 (except environmental exposure), 28 and 52. Patients on omalizumab were also more likely to achieve clinically significant improvements in AQoL during the course of the study. Overall, almost 70% of patients and investigators rated treatment with omalizumab as ""excellent/good"", compared with similar to40% of placebo recipients. Clinical studies show that omalizumab enhances disease control whilst reducing corticosteroid consumption in patients with allergic asthma. The results of the present study show that these changes are paralleled by improvements in asthma-related quality of life that are meaningful to such patients."	29	91	2002	7	10.1183/09031936.02.00016502	Respiratory System
Indoor and outdoor BTX levels in German cities. On the basis of the ongoing study INGA (INdoor exposure and Genetics in Asthma), Germany's most detailed and standardized epidemiological study on indoor exposure to both allergens in house dust and volatile compounds in the air of the home environment has been performed. The purpose of this paper is to describe the spatial and seasonal variability of indoor and outdoor BTX (Benzene, toluene, ethyl benzene, ortho-xylene, meta- and para-xylene) concentrations for the study period from June 1995 to November 1996. Within this framework, air concentrations of volatile organic compounds (BTX) were measured in 204 households in Erfurt (Eastern Germany) and 201 households in Hamburg (Western Germany). BTX sampling was conducted over one week using OVM 3500 passive diffusion sampling devices in the indoor (living room and bedroom) and outdoor environment (outside the window of the living room). Indoor and outdoor median BTX concentrations in Erfurt were slightly, but significantly higher than those in Hamburg. This gap was most pronounced in the levels of indoor toluene (37.3 mug/m(3) for Erfurt and 20.5 mug/m(3) for Hamburg, P < 0.0001). In both cities, winter indoor and outdoor concentrations for the five compounds exceeded the summer values. Outdoor concentrations of ethyl benzene and ortho-xylene were very low (50% < L.D.). In general, the indoor BTX air concentrations were significantly higher than the outdoor concentrations, the lowest I/O ratios were found in the case of benzene. Living room and bedroom values for the five compounds were highly correlated (Spearman coefficient 0.5-0.9). Despite the better insulation of the homes in West Germany, no indication for the expected higher indoor concentrations of BTX in the West could be found. The strong and yet undiscovered indoor source for toluene in East Germany might lead to a further increase in the indoor air load in those homes in the East, which undergo renovations which will lead to improved insulation (C) 2001 Elsevier Science B.V. All rights reserved.. volatile organic compounds| btx| passive sampling| indoor air quality| homes|volatile organic-compounds| eastern germany| air| hamburg| erfurt| homes| emissions.	FEB 21-2001	volatile organic compounds| btx| passive sampling| indoor air quality| homes|volatile organic-compounds| eastern germany| air| hamburg| erfurt| homes| emissions	Schneider, P; Gebefugi, I; Richter, K; Wolke, G; Schnelle, J; Wichmann, HE; Heinrich, J	Indoor and outdoor BTX levels in German cities		SCIENCE OF THE TOTAL ENVIRONMENT	volatile organic compounds; BTX; passive sampling; indoor air quality; homes	VOLATILE ORGANIC-COMPOUNDS; EASTERN GERMANY; AIR; HAMBURG; ERFURT; HOMES; EMISSIONS	On the basis of the ongoing study INGA (INdoor exposure and Genetics in Asthma), Germany's most detailed and standardized epidemiological study on indoor exposure to both allergens in house dust and volatile compounds in the air of the home environment has been performed. The purpose of this paper is to describe the spatial and seasonal variability of indoor and outdoor BTX (Benzene, toluene, ethyl benzene, ortho-xylene, meta- and para-xylene) concentrations for the study period from June 1995 to November 1996. Within this framework, air concentrations of volatile organic compounds (BTX) were measured in 204 households in Erfurt (Eastern Germany) and 201 households in Hamburg (Western Germany). BTX sampling was conducted over one week using OVM 3500 passive diffusion sampling devices in the indoor (living room and bedroom) and outdoor environment (outside the window of the living room). Indoor and outdoor median BTX concentrations in Erfurt were slightly, but significantly higher than those in Hamburg. This gap was most pronounced in the levels of indoor toluene (37.3 mug/m(3) for Erfurt and 20.5 mug/m(3) for Hamburg, P < 0.0001). In both cities, winter indoor and outdoor concentrations for the five compounds exceeded the summer values. Outdoor concentrations of ethyl benzene and ortho-xylene were very low (50% < L.D.). In general, the indoor BTX air concentrations were significantly higher than the outdoor concentrations, the lowest I/O ratios were found in the case of benzene. Living room and bedroom values for the five compounds were highly correlated (Spearman coefficient 0.5-0.9). Despite the better insulation of the homes in West Germany, no indication for the expected higher indoor concentrations of BTX in the West could be found. The strong and yet undiscovered indoor source for toluene in East Germany might lead to a further increase in the indoor air load in those homes in the East, which undergo renovations which will lead to improved insulation (C) 2001 Elsevier Science B.V. All rights reserved.	32	91	2001	11	10.1016/S0048-9697(00)00766-X	Environmental Sciences & Ecology
The effects of ambient air pollution on school absenteeism due to respiratory illnesses. We investigated the relations between ozone (O-3), nitrogen dioxide (NO2), and respirable particles less than 10 mum in diameter (PM10) and school absenteeism in a cohort of 4th-grade school children who resided in 12 southern California communities. An active surveillance system ascertained the numbers and types of absences during the first 6 months of 1996. Pollutants were measured hourly at central-site monitors in each of the 12 communities. To examine acute effects of air pollution on absence rates, we fitted a two-stage time series model to the absence count data that included distributed lag effects of exposure adjusted for long-term pollutant levels. Short-term change in O-3, but not NO2 or PM10, was associated with a substantial increase in school absences from both upper and lower respiratory illness. An increase of 20 ppb of O-3 was associated with an increase of 62.9% [95% confidence interval (95% CI) = 18.4-124.1%] for illness-related absence rates, 82.9% (95% CI = 3.9-222.0%) for respiratory illnesses, 45.1% (95% CI = 21.3-73.7%) for upper respiratory illnesses, and 173.9% (95% CI = 91.3-292.3%) for lower respiratory illnesses with wet cough. The short-term effects of a 20-ppb change of O-3 on illness-related absenteeism were larger in communities with lower long-term average PM10 [223.5% (95% CI = 90.4-449.7)] compared with communities with high average levels [38.1% (95% CI = 8.5-75.8)]. Increased school absenteeism from O-3 exposure in children is an important adverse effect of ambient air pollution worthy of public policy consideration.. air pollution| ozone| respiratory illnesses and children| school absenteeism|southern california communities| pulmonary-function| differing levels| mexico-city| children| asthma| particulate| exposures| morbidity| symptoms.	JAN-2001	air pollution| ozone| respiratory illnesses and children| school absenteeism|southern california communities| pulmonary-function| differing levels| mexico-city| children| asthma| particulate| exposures| morbidity| symptoms	Gilliland, FD; Berhane, K; Rapaport, EB; Thomas, DC; Avol, E; Gauderman, WJ; London, SJ; Margolis, HG; McConnell, R; Islam, KT; Peters, JM	The effects of ambient air pollution on school absenteeism due to respiratory illnesses		EPIDEMIOLOGY	air pollution; ozone; respiratory illnesses and children; school absenteeism	SOUTHERN CALIFORNIA COMMUNITIES; PULMONARY-FUNCTION; DIFFERING LEVELS; MEXICO-CITY; CHILDREN; ASTHMA; PARTICULATE; EXPOSURES; MORBIDITY; SYMPTOMS	We investigated the relations between ozone (O-3), nitrogen dioxide (NO2), and respirable particles less than 10 mum in diameter (PM10) and school absenteeism in a cohort of 4th-grade school children who resided in 12 southern California communities. An active surveillance system ascertained the numbers and types of absences during the first 6 months of 1996. Pollutants were measured hourly at central-site monitors in each of the 12 communities. To examine acute effects of air pollution on absence rates, we fitted a two-stage time series model to the absence count data that included distributed lag effects of exposure adjusted for long-term pollutant levels. Short-term change in O-3, but not NO2 or PM10, was associated with a substantial increase in school absences from both upper and lower respiratory illness. An increase of 20 ppb of O-3 was associated with an increase of 62.9% [95% confidence interval (95% CI) = 18.4-124.1%] for illness-related absence rates, 82.9% (95% CI = 3.9-222.0%) for respiratory illnesses, 45.1% (95% CI = 21.3-73.7%) for upper respiratory illnesses, and 173.9% (95% CI = 91.3-292.3%) for lower respiratory illnesses with wet cough. The short-term effects of a 20-ppb change of O-3 on illness-related absenteeism were larger in communities with lower long-term average PM10 [223.5% (95% CI = 90.4-449.7)] compared with communities with high average levels [38.1% (95% CI = 8.5-75.8)]. Increased school absenteeism from O-3 exposure in children is an important adverse effect of ambient air pollution worthy of public policy consideration.	45	91	2001	12	10.1097/00001648-200101000-00009	Public, Environmental & Occupational Health
Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge. We compared for the first time the therapeutic potential of a specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, with anti-VLA-4 and anti-IL-5 in a model of secondary allergen exposure of previously sensitized and challenged mice. To address these issues, mice were sensitized and challenged with ovalbumin (OVA) (primary challenge). Six weeks later, sensitized/challenged mice were reexposed to OVA (secondary challenge) and airway response (resistance [RL] and dynamic compliance [Cdyn]) to inhaled methacholine was monitored. After secondary OVA challenge, Rr significantly increased as did the number of lung inflammatory cells and IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF). Administration of rolipram, in a dose-dependent manner, significantly prevented both changes in Rr and Cdyn, as well as eosinophil, lymphocyte, and neutrophil accumulation in the BALF; IL-4 and IL-5 levels in BALF were also significantly reduced. In contrast, treatment with anti-VLA-4 and anti-IL-5 only prevented changes in RL and eosinophil numbers and IL-5 production in BALF. Further, goblet cell hyperplasia was suppressed only by treatment with rolipram. None of the treatments affected OVA-specific antibody levels. These studies confirm that IL-5 dependent eosinophilic inflammation plays an essential role in the development of certain aspects of airway function after rechallenge of sensitized mice and that lymphocytes and neutrophils are also important in the development of altered airway function. The use of agents that inhibit PDE4 may have an important role in the treatment of asthma in previously sensitized mice.. human neutrophil functions| murine model| pde inhibitors| atopic asthma| type-4| lung| eosinophilia| responses| rolipram| camp.	JAN-2001	human neutrophil functions| murine model| pde inhibitors| atopic asthma| type-4| lung| eosinophilia| responses| rolipram| camp	Kanehiro, A; Ikemura, T; Makela, MJ; Lahn, M; Joetham, A; Dakhama, A; Gelfand, EW	Inhibition of phosphodiesterase 4 attenuates airway hyperresponsiveness and airway inflammation in a model of secondary allergen challenge		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		HUMAN NEUTROPHIL FUNCTIONS; MURINE MODEL; PDE INHIBITORS; ATOPIC ASTHMA; TYPE-4; LUNG; EOSINOPHILIA; RESPONSES; ROLIPRAM; CAMP	We compared for the first time the therapeutic potential of a specific phosphodiesterase 4 (PDE4) inhibitor, rolipram, with anti-VLA-4 and anti-IL-5 in a model of secondary allergen exposure of previously sensitized and challenged mice. To address these issues, mice were sensitized and challenged with ovalbumin (OVA) (primary challenge). Six weeks later, sensitized/challenged mice were reexposed to OVA (secondary challenge) and airway response (resistance [RL] and dynamic compliance [Cdyn]) to inhaled methacholine was monitored. After secondary OVA challenge, Rr significantly increased as did the number of lung inflammatory cells and IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF). Administration of rolipram, in a dose-dependent manner, significantly prevented both changes in Rr and Cdyn, as well as eosinophil, lymphocyte, and neutrophil accumulation in the BALF; IL-4 and IL-5 levels in BALF were also significantly reduced. In contrast, treatment with anti-VLA-4 and anti-IL-5 only prevented changes in RL and eosinophil numbers and IL-5 production in BALF. Further, goblet cell hyperplasia was suppressed only by treatment with rolipram. None of the treatments affected OVA-specific antibody levels. These studies confirm that IL-5 dependent eosinophilic inflammation plays an essential role in the development of certain aspects of airway function after rechallenge of sensitized mice and that lymphocytes and neutrophils are also important in the development of altered airway function. The use of agents that inhibit PDE4 may have an important role in the treatment of asthma in previously sensitized mice.	33	91	2001	12		General & Internal Medicine; Respiratory System
Effects of indoor painting and smoking on airway symptoms in atopy risk children in the first year of life - results of the LARS-study. Introduction: The Leipzig Allergy High-Risk Children Study (LARS) is a prospective nested cohort control study about the influence of chemical indoor exposure in dwellings on the health outcome of atopy-risk children during the first years of life. Design and Methods: 475 premature children and children with allergic risk factors have been selected out of the 1995/1996 birth cohort in the city of Leipzig. Twenty-five volatile organic compounds (VOC) were measured in the infant's bedrooms using passive sampling systems for 4 weeks after birth. The babies underwent a medical examination at the age of sis weeks and 1 year. The parents answered a questionnaire. Results: Correlations between VOC exposures and infections were calculated by multiple logistic regression. Selected VOC show a direct association to actually painted dwellings (OR = 2.4; 95 % Cl 1.1-5.3). An increase of risk of pulmonary infections was observed in infants aged 6 weeks if restoration (painting OR 5.6; 95 % Cl 1.3-24.0) or flooring connected with painting had occurred during the pregnancy period. Higher concentration of styrene (>2.0 mu g/m(3), indicator for flooring) elevated the risk of pulmonary infections in six-week-old infants (OR = 2.1; 95 % Cl 1.1-4.2). Environmental benzene > 5.6 mu g/m(3) increased the risk of airway infections in six-week-old babies (OR = 2.4; 95 % Cl 1.28-4.48). Smoking in the dwelling (OR = 2.0; 95 % Cl 1.1-3.5) as well as restoration (OR = 1.9; 95 % Cl 1.1-3.5) are also risk factors of the development of wheezing in the one-year-old child. Conclusions: The data give indications in order to prevent allergies and chronic lung diseases in atopy risk children exposure to chemicals from indoor air should be minimised from birth on.. atopy risk children| air pollution| voc| restoration| smoking| pulmonary infections|volatile organic-compounds| asthma.	MAR-2000	atopy risk children| air pollution| voc| restoration| smoking| pulmonary infections|volatile organic-compounds| asthma	Diez, U; Kroessner, T; Rehwagen, M; Richter, M; Wetzig, H; Schulz, R; Borte, M; Metzner, G; Krumbiegel, P; Herbarth, O	Effects of indoor painting and smoking on airway symptoms in atopy risk children in the first year of life - results of the LARS-study		INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH	atopy risk children; air pollution; VOC; restoration; smoking; pulmonary infections	VOLATILE ORGANIC-COMPOUNDS; ASTHMA	Introduction: The Leipzig Allergy High-Risk Children Study (LARS) is a prospective nested cohort control study about the influence of chemical indoor exposure in dwellings on the health outcome of atopy-risk children during the first years of life. Design and Methods: 475 premature children and children with allergic risk factors have been selected out of the 1995/1996 birth cohort in the city of Leipzig. Twenty-five volatile organic compounds (VOC) were measured in the infant's bedrooms using passive sampling systems for 4 weeks after birth. The babies underwent a medical examination at the age of sis weeks and 1 year. The parents answered a questionnaire. Results: Correlations between VOC exposures and infections were calculated by multiple logistic regression. Selected VOC show a direct association to actually painted dwellings (OR = 2.4; 95 % Cl 1.1-5.3). An increase of risk of pulmonary infections was observed in infants aged 6 weeks if restoration (painting OR 5.6; 95 % Cl 1.3-24.0) or flooring connected with painting had occurred during the pregnancy period. Higher concentration of styrene (>2.0 mu g/m(3), indicator for flooring) elevated the risk of pulmonary infections in six-week-old infants (OR = 2.1; 95 % Cl 1.1-4.2). Environmental benzene > 5.6 mu g/m(3) increased the risk of airway infections in six-week-old babies (OR = 2.4; 95 % Cl 1.28-4.48). Smoking in the dwelling (OR = 2.0; 95 % Cl 1.1-3.5) as well as restoration (OR = 1.9; 95 % Cl 1.1-3.5) are also risk factors of the development of wheezing in the one-year-old child. Conclusions: The data give indications in order to prevent allergies and chronic lung diseases in atopy risk children exposure to chemicals from indoor air should be minimised from birth on.	19	91	2000	6	10.1078/S1438-4639(04)70004-8	Public, Environmental & Occupational Health; Infectious Diseases
Immunology of atopic eczema: overcoming the Th1/Th2 paradigm. Atopic eczema (AE) is a challenge for modern medicine, because it is prevalent, severely affects quality of life of patients and their families, and causes high socioeconomic costs. The pathogenesis of AE is complex. While initial studies suggested a Th2 deviation as primary reason for the disease, numerous studies addressed a genetically predetermined impaired epidermal barrier as leading cause in a subgroup of patients. Recently, immune changes beyond the initial Th2 concept were defined in AE, with a role for specialized dendritic cells as well as newly identified T helper cell subsets such as Th17 and Th22 cells. Furthermore, trigger factors are expanded beyond classical Th2 allergens such as pollen or house dust mites to microbial products as well as self-antigens. This review pieces together our current understanding of immune as well as barrier abnormalities into the pathogenesis mosaic of AE.. dendritic cell| dermatitis| eczema| immunology| t cell|thymic stromal lymphopoietin| fc-epsilon-ri| anti-cd20 rituximab treatment| ifn-gamma response| allergic contact| dendritic cells| patch test| in-situ| t-cells| keratinocyte differentiation.	AUG-2013	dendritic cell| dermatitis| eczema| immunology| t cell|thymic stromal lymphopoietin| fc-epsilon-ri| anti-cd20 rituximab treatment| ifn-gamma response| allergic contact| dendritic cells| patch test| in-situ| t-cells| keratinocyte differentiation	Eyerich, K; Novak, N	Immunology of atopic eczema: overcoming the Th1/Th2 paradigm		ALLERGY	dendritic cell; dermatitis; eczema; immunology; T cell	THYMIC STROMAL LYMPHOPOIETIN; FC-EPSILON-RI; ANTI-CD20 RITUXIMAB TREATMENT; IFN-GAMMA RESPONSE; ALLERGIC CONTACT; DENDRITIC CELLS; PATCH TEST; IN-SITU; T-CELLS; KERATINOCYTE DIFFERENTIATION	Atopic eczema (AE) is a challenge for modern medicine, because it is prevalent, severely affects quality of life of patients and their families, and causes high socioeconomic costs. The pathogenesis of AE is complex. While initial studies suggested a Th2 deviation as primary reason for the disease, numerous studies addressed a genetically predetermined impaired epidermal barrier as leading cause in a subgroup of patients. Recently, immune changes beyond the initial Th2 concept were defined in AE, with a role for specialized dendritic cells as well as newly identified T helper cell subsets such as Th17 and Th22 cells. Furthermore, trigger factors are expanded beyond classical Th2 allergens such as pollen or house dust mites to microbial products as well as self-antigens. This review pieces together our current understanding of immune as well as barrier abnormalities into the pathogenesis mosaic of AE.	102	90	2013	9	10.1111/all.12184	Allergy; Immunology
Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease The REDUCE Randomized Clinical Trial. Importance International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown. Objective To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids. Design, Setting, and Patients REDUCE (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (>= 20 pack-years) without a history of asthma, from March 2006 through February 2011. Interventions Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%. Main Outcome and Measure Time to next exacerbation within 180 days. Results Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P=.006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P=.005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P<.001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently. Conclusions and Relevance In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.. systemic glucocorticoids| oral prednisone| copd| mortality.	JUN 5-2013	systemic glucocorticoids| oral prednisone| copd| mortality	Leuppi, JD; Schuetz, P; Bingisser, R; Bodmer, M; Briel, M; Drescher, T; Duerring, U; Henzen, C; Leibbrandt, Y; Maier, S; Miedinger, D; Muller, B; Scherr, A; Schindler, C; Stoeckli, R; Viatte, S; von Garnier, C; Tamm, M; Rutishauser, J	Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease The REDUCE Randomized Clinical Trial		JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION		SYSTEMIC GLUCOCORTICOIDS; ORAL PREDNISONE; COPD; MORTALITY	Importance International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown. Objective To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids. Design, Setting, and Patients REDUCE (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (>= 20 pack-years) without a history of asthma, from March 2006 through February 2011. Interventions Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%. Main Outcome and Measure Time to next exacerbation within 180 days. Results Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P=.006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P=.005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P<.001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently. Conclusions and Relevance In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.	25	90	2013	9	10.1001/jama.2013.5023	General & Internal Medicine
Simultaneous magnetic resonance imaging of ventilation distribution and gas uptake in the human lung using hyperpolarized xenon-129. Despite a myriad of technical advances in medical imaging, as well as the growing need to address the global impact of pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, on health and quality of life, it remains challenging to obtain in vivo regional depiction and quantification of the most basic physiological functions of the lung-gas delivery to the airspaces and gas uptake by the lung parenchyma and blood-in a manner suitable for routine application in humans. We report a method based on MRI of hyperpolarized xenon-129 that permits simultaneous observation of the 3D distributions of ventilation (gas delivery) and gas uptake, as well as quantification of regional gas uptake based on the associated ventilation. Subjects with lung disease showed variations in gas uptake that differed from those in ventilation in many regions, suggesting that gas uptake as measured by this technique reflects such features as underlying pathological alterations of lung tissue or of local blood flow. Furthermore, the ratio of the signal associated with gas uptake to that associated with ventilation was substantially altered in subjects with lung disease compared with healthy subjects. This MRI-based method provides a way to quantify relationships among gas delivery, exchange, and transport, and appears to have significant potential to provide more insight into lung disease.. gas exchange| pulmonary function| pulmonary ventilation|air spaces| he-3 gas| in-vivo| mri| dynamics| nmr.	DEC 14-2010	gas exchange| pulmonary function| pulmonary ventilation|air spaces| he-3 gas| in-vivo| mri| dynamics| nmr	Mugler, JP; Altes, TA; Ruset, IC; Dregely, IM; Mata, JF; Miller, GW; Ketel, S; Ketel, J; Hersman, FW; Ruppert, K	Simultaneous magnetic resonance imaging of ventilation distribution and gas uptake in the human lung using hyperpolarized xenon-129		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	gas exchange; pulmonary function; pulmonary ventilation	AIR SPACES; HE-3 GAS; IN-VIVO; MRI; DYNAMICS; NMR	Despite a myriad of technical advances in medical imaging, as well as the growing need to address the global impact of pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, on health and quality of life, it remains challenging to obtain in vivo regional depiction and quantification of the most basic physiological functions of the lung-gas delivery to the airspaces and gas uptake by the lung parenchyma and blood-in a manner suitable for routine application in humans. We report a method based on MRI of hyperpolarized xenon-129 that permits simultaneous observation of the 3D distributions of ventilation (gas delivery) and gas uptake, as well as quantification of regional gas uptake based on the associated ventilation. Subjects with lung disease showed variations in gas uptake that differed from those in ventilation in many regions, suggesting that gas uptake as measured by this technique reflects such features as underlying pathological alterations of lung tissue or of local blood flow. Furthermore, the ratio of the signal associated with gas uptake to that associated with ventilation was substantially altered in subjects with lung disease compared with healthy subjects. This MRI-based method provides a way to quantify relationships among gas delivery, exchange, and transport, and appears to have significant potential to provide more insight into lung disease.	24	90	2010	6	10.1073/pnas.1011912107	Science & Technology - Other Topics
Therapeutic potential of complement modulation. The complement system is an essential component of innate immunity that has been more recently recognized as an unexpected player in various pathological states. These include age-related macular degeneration, atypical haemolytic uraemic syndrome, allergy, foetal loss, and axonal and myelin degradation after trauma. Its importance has also been recognized in physiological processes including haematopoietic stem cell homing to the bone marrow, liver regeneration and modulation of adaptive immune responses. Although the complement system has long been known to be involved in autoimmune and inflammatory diseases, few agents that target the complement system are currently approved for clinical use. However, renewed interest in modulating this system in various pathological conditions has emerged, and several agents are now in development.. hemolytic-uremic syndrome| mannose-binding lectin| elevation myocardial-infarction| entire c1qr(2)s(2) complex| traumatic brain-injury| th2 effector functions| alternative pathway| factor-h| c1 inhibitor| factor-b.	JAN-2010	hemolytic-uremic syndrome| mannose-binding lectin| elevation myocardial-infarction| entire c1qr(2)s(2) complex| traumatic brain-injury| th2 effector functions| alternative pathway| factor-h| c1 inhibitor| factor-b	Wagner, E; Frank, MM	Therapeutic potential of complement modulation		NATURE REVIEWS DRUG DISCOVERY		HEMOLYTIC-UREMIC SYNDROME; MANNOSE-BINDING LECTIN; ELEVATION MYOCARDIAL-INFARCTION; ENTIRE C1QR(2)S(2) COMPLEX; TRAUMATIC BRAIN-INJURY; TH2 EFFECTOR FUNCTIONS; ALTERNATIVE PATHWAY; FACTOR-H; C1 INHIBITOR; FACTOR-B	The complement system is an essential component of innate immunity that has been more recently recognized as an unexpected player in various pathological states. These include age-related macular degeneration, atypical haemolytic uraemic syndrome, allergy, foetal loss, and axonal and myelin degradation after trauma. Its importance has also been recognized in physiological processes including haematopoietic stem cell homing to the bone marrow, liver regeneration and modulation of adaptive immune responses. Although the complement system has long been known to be involved in autoimmune and inflammatory diseases, few agents that target the complement system are currently approved for clinical use. However, renewed interest in modulating this system in various pathological conditions has emerged, and several agents are now in development.	122	90	2010	14	10.1038/nrd3011	Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
Occupational exposures and the risk of COPD: dusty trades revisited. Background: The contribution of occupational exposures to chronic obstructive pulmonary disease (COPD) and, in particular, their potential interaction with cigarette smoking remains underappreciated. Methods: Data from the FLOW study of 1202 subjects with COPD (of which 742 had disease classified as stage II or above by Global Obstructive Lung Disease (GOLD) criteria) and 302 referent subjects matched by age, sex and race recruited from a large managed care organisation were analysed. Occupational exposures were assessed using two methods: self-reported exposure to vapours, gas, dust or fumes on the longest held job (VGDF) and a job exposure matrix (JEM) for probability of exposure based on occupation. Multivariate analysis was used to control for age, sex, race and smoking history. The odds ratio (OR) and adjusted population attributable fraction (PAF) associated with occupational exposure were calculated. Results: VGDF exposure was associated with an increased risk of COPD (OR 2.11; 95% CI 1.59 to 2.82) and a PAF of 31% (95% CI 22% to 39%). The risk associated with high probability of workplace exposure by JEM was similar (OR 2.27; 95% CI 1.46 to 3.52), although the PAF was lower (13%; 95% CI 8% to 18%). These estimates were not substantively different when the analysis was limited to COPD GOLD stage II or above. Joint exposure to both smoking and occupational factors markedly increased the risk of COPD (OR 14.1; 95% CI 9.33 to 21.2). Conclusions: Workplace exposures are strongly associated with an increased risk of COPD. On a population level, prevention of both smoking and occupational exposure, and especially both together, is needed to prevent the global burden of disease.. obstructive pulmonary-disease| work disability| health outcomes| us population| lung-function| asthma| burden| association| prevalence| limitation.	JAN-2009	obstructive pulmonary-disease| work disability| health outcomes| us population| lung-function| asthma| burden| association| prevalence| limitation	Blanc, PD; Iribarren, C; Trupin, L; Earnest, G; Katz, PP; Balmes, J; Sidney, S; Eisner, MD	Occupational exposures and the risk of COPD: dusty trades revisited		THORAX		OBSTRUCTIVE PULMONARY-DISEASE; WORK DISABILITY; HEALTH OUTCOMES; US POPULATION; LUNG-FUNCTION; ASTHMA; BURDEN; ASSOCIATION; PREVALENCE; LIMITATION	Background: The contribution of occupational exposures to chronic obstructive pulmonary disease (COPD) and, in particular, their potential interaction with cigarette smoking remains underappreciated. Methods: Data from the FLOW study of 1202 subjects with COPD (of which 742 had disease classified as stage II or above by Global Obstructive Lung Disease (GOLD) criteria) and 302 referent subjects matched by age, sex and race recruited from a large managed care organisation were analysed. Occupational exposures were assessed using two methods: self-reported exposure to vapours, gas, dust or fumes on the longest held job (VGDF) and a job exposure matrix (JEM) for probability of exposure based on occupation. Multivariate analysis was used to control for age, sex, race and smoking history. The odds ratio (OR) and adjusted population attributable fraction (PAF) associated with occupational exposure were calculated. Results: VGDF exposure was associated with an increased risk of COPD (OR 2.11; 95% CI 1.59 to 2.82) and a PAF of 31% (95% CI 22% to 39%). The risk associated with high probability of workplace exposure by JEM was similar (OR 2.27; 95% CI 1.46 to 3.52), although the PAF was lower (13%; 95% CI 8% to 18%). These estimates were not substantively different when the analysis was limited to COPD GOLD stage II or above. Joint exposure to both smoking and occupational factors markedly increased the risk of COPD (OR 14.1; 95% CI 9.33 to 21.2). Conclusions: Workplace exposures are strongly associated with an increased risk of COPD. On a population level, prevention of both smoking and occupational exposure, and especially both together, is needed to prevent the global burden of disease.	39	90	2009	7	10.1136/thx.2008.099390	Respiratory System
Increased circulating fibrocytes in asthma with chronic airflow obstruction. Rationale A proportion of patients with asthma present with chronic airflow obstruction (CAO). We hypothesized that this effect may result from increased activity of circulating fibroblast-like progenitor cells (fibrocytes) that could home to the airway mucosal wall. Objectives: To compare the proportion, proliferation, and differentiation of circulating fibrocytes from patients with asthma with CAO or no airflow obstruction (NOA) and control subjects. Methods: We investigated circulating fibrocytes in 11 patients with asthma with CAO and a rapid decline in FEV(1), 9 patients with asthma with NOA, and 10 nonasthmatic control subjects. Blood nonadherent non-T (NANT) cells were incubated with fetal calf serum or each patient's own serum and fibrocytes expressing CD34, CD45, and collagen I with a-smooth muscle actin were identified by flow cytometry. Measurements and Main Results: A higher percentage of circulating fibrocytes in NANT cells was found in patients with CAO when compared with patients with NOA and control subjects. In CAO, the slope of the yearly decline in FEV(1) correlated with circulating fibrocytes (r = -0.756, n = 11, P < 0.01). When NANT cells from patients with CAO were cultured in the patients' own sera, more fibrocytes were detected than when cultured in sera from patients with NOA or from normal subjects. An anti-transforming growth factor (TGF)-beta(1)-neutralizing antibody inhibited a-smooth muscle actin-positive fibrocyte transformation from NANT cells of patients with CAO. Serum TGF-beta(1) levels were higher in patients with CAO than in patients with NOA or in normal subjects. Conclusions: Circulating fibrocytes are increased in patients with asthma with CAO and can be transformed by TGF-beta(1) to myofibroblasts. Fibrocytes may contribute to airway obstruction in asthma.. asthma| fibrocytes| myofibroblasts| transforming growth factor-beta| airway remodeling|peripheral-blood fibrocytes| reticular basement-membrane| tissue-repair| cells| differentiation| expression| fibrosis| growth| angiogenesis| inflammation.	SEP 15-2008	asthma| fibrocytes| myofibroblasts| transforming growth factor-beta| airway remodeling|peripheral-blood fibrocytes| reticular basement-membrane| tissue-repair| cells| differentiation| expression| fibrosis| growth| angiogenesis| inflammation	Wang, CH; Huang, CD; Lin, HC; Lee, KY; Lin, SM; Liu, CY; Huang, KH; Ko, YS; Chung, KF; Kuo, HP	Increased circulating fibrocytes in asthma with chronic airflow obstruction		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; fibrocytes; myofibroblasts; transforming growth factor-beta; airway remodeling	PERIPHERAL-BLOOD FIBROCYTES; RETICULAR BASEMENT-MEMBRANE; TISSUE-REPAIR; CELLS; DIFFERENTIATION; EXPRESSION; FIBROSIS; GROWTH; ANGIOGENESIS; INFLAMMATION	Rationale A proportion of patients with asthma present with chronic airflow obstruction (CAO). We hypothesized that this effect may result from increased activity of circulating fibroblast-like progenitor cells (fibrocytes) that could home to the airway mucosal wall. Objectives: To compare the proportion, proliferation, and differentiation of circulating fibrocytes from patients with asthma with CAO or no airflow obstruction (NOA) and control subjects. Methods: We investigated circulating fibrocytes in 11 patients with asthma with CAO and a rapid decline in FEV(1), 9 patients with asthma with NOA, and 10 nonasthmatic control subjects. Blood nonadherent non-T (NANT) cells were incubated with fetal calf serum or each patient's own serum and fibrocytes expressing CD34, CD45, and collagen I with a-smooth muscle actin were identified by flow cytometry. Measurements and Main Results: A higher percentage of circulating fibrocytes in NANT cells was found in patients with CAO when compared with patients with NOA and control subjects. In CAO, the slope of the yearly decline in FEV(1) correlated with circulating fibrocytes (r = -0.756, n = 11, P < 0.01). When NANT cells from patients with CAO were cultured in the patients' own sera, more fibrocytes were detected than when cultured in sera from patients with NOA or from normal subjects. An anti-transforming growth factor (TGF)-beta(1)-neutralizing antibody inhibited a-smooth muscle actin-positive fibrocyte transformation from NANT cells of patients with CAO. Serum TGF-beta(1) levels were higher in patients with CAO than in patients with NOA or in normal subjects. Conclusions: Circulating fibrocytes are increased in patients with asthma with CAO and can be transformed by TGF-beta(1) to myofibroblasts. Fibrocytes may contribute to airway obstruction in asthma.	36	90	2008	9	10.1164/rccm.200710-1557OC	General & Internal Medicine; Respiratory System
Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation. Background Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. Objective Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants. Methods In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. Results Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17-0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16-0.87), P=0.023] at age 2 years, when adjusted with probiotic use. Conclusion The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.. atopic| crp| iga| ige| il-10| oral tolerance| probiotic| regulatory cells|placebo-controlled trial| oral tolerance induction| cows milk allergy| atopic-dermatitis| double-blind| antibody-responses| hygiene hypothesis| t-cells| children| prevention.	APR-2008	atopic| crp| iga| ige| il-10| oral tolerance| probiotic| regulatory cells|placebo-controlled trial| oral tolerance induction| cows milk allergy| atopic-dermatitis| double-blind| antibody-responses| hygiene hypothesis| t-cells| children| prevention	Marschan, E; Kuitunen, M; Kukkonen, K; Poussa, T; Sarnesto, A; Haahtela, T; Korpela, R; Savilahti, E; Vaarala, O	Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation		CLINICAL AND EXPERIMENTAL ALLERGY	atopic; CRP; IgA; IgE; IL-10; oral tolerance; probiotic; regulatory cells	PLACEBO-CONTROLLED TRIAL; ORAL TOLERANCE INDUCTION; COWS MILK ALLERGY; ATOPIC-DERMATITIS; DOUBLE-BLIND; ANTIBODY-RESPONSES; HYGIENE HYPOTHESIS; T-CELLS; CHILDREN; PREVENTION	Background Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. Objective Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants. Methods In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. Results Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17-0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16-0.87), P=0.023] at age 2 years, when adjusted with probiotic use. Conclusion The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.	40	90	2008	8	10.1111/j.1365-2222.2008.02942.x	Allergy; Immunology
Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients. Controlled studies have shown that monitoring of the exhaled nitric oxide fraction (FeNO) improves asthma management. However, the studies seldom consider the full range of patients seen in clinical practise. In the present study, the ability of FeNO to reflect asthma control over time is investigated in a regular clinical setting, and meaningful FeNO cut-off points and changes are identified. Answers to the Asthma Control Questionnaire and FeNO were recorded at least once in 341 unselected asthma patients. The whole population and subgroups were considered, i.e. both inhaled corticosteroid (ICS)-naive and low or high-to-medium (<= or >500 mu g beclomethasone dipropionate equivalents(.)day(-1)) ICS-dose groups. An FeNo decrease <40% or increase <30% precludes asthma control optimisation or deterioration, respectively (negative predictive value 79 and 82%, respectively). In the present study's low-dose group, a decrease >40% indicated asthma control optimisation (positive predictive value (PPV) 83%). In ICS-naive patients, FeNO >35 ppb predicted asthma control improvement in response to ICS (PPV 68%). In most cases, forced expiratory volume in one second assessments were not useful. In conclusion, in a given patient, exhaled nitric oxide fraction was found to be significantly related to asthma control over time. The overall ability of exhaled nitric oxide fraction to reflect asthma control was reduced in patients using high doses of inhaled corticosteroids. Forced expiratory volume in one second had little additional value in assessing asthma control.. asthma control| exhaled nitric oxide| lung function|randomized controlled-trial| guide| questionnaire| exacerbations| markers| air.	MAR-2008	asthma control| exhaled nitric oxide| lung function|randomized controlled-trial| guide| questionnaire| exacerbations| markers| air	Michils, A; Baldassarre, S; Van Muylem, A	Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients		EUROPEAN RESPIRATORY JOURNAL	asthma control; exhaled nitric oxide; lung function	RANDOMIZED CONTROLLED-TRIAL; GUIDE; QUESTIONNAIRE; EXACERBATIONS; MARKERS; AIR	Controlled studies have shown that monitoring of the exhaled nitric oxide fraction (FeNO) improves asthma management. However, the studies seldom consider the full range of patients seen in clinical practise. In the present study, the ability of FeNO to reflect asthma control over time is investigated in a regular clinical setting, and meaningful FeNO cut-off points and changes are identified. Answers to the Asthma Control Questionnaire and FeNO were recorded at least once in 341 unselected asthma patients. The whole population and subgroups were considered, i.e. both inhaled corticosteroid (ICS)-naive and low or high-to-medium (<= or >500 mu g beclomethasone dipropionate equivalents(.)day(-1)) ICS-dose groups. An FeNo decrease <40% or increase <30% precludes asthma control optimisation or deterioration, respectively (negative predictive value 79 and 82%, respectively). In the present study's low-dose group, a decrease >40% indicated asthma control optimisation (positive predictive value (PPV) 83%). In ICS-naive patients, FeNO >35 ppb predicted asthma control improvement in response to ICS (PPV 68%). In most cases, forced expiratory volume in one second assessments were not useful. In conclusion, in a given patient, exhaled nitric oxide fraction was found to be significantly related to asthma control over time. The overall ability of exhaled nitric oxide fraction to reflect asthma control was reduced in patients using high doses of inhaled corticosteroids. Forced expiratory volume in one second had little additional value in assessing asthma control.	30	90	2008	8	10.1183/09031936.00020407	Respiratory System
Work, obesity, and occupational safety and health. There is increasing evidence that obesity and overweight may be related, in part, to adverse work conditions. In particular, the risk of obesity may increase in high-demand, low-control work environments, and for those who work long hours. In addition, obesity may modify the risk for vibration-induced injury and certain occupational musculoskeletal disorders. We hypothesized that obesity may also be a co-risk factor for the development of occupational asthma and cardiovascular disease that and it may modify the worker's response to occupational stress, immune response to chemical exposures, and risk of disease from occupational neurotoxins. We developed 5 conceptual models of the interrelationship of work, obesity, and occupational safety and health and highlighted the ethical, legal, and social issues related to fuller consideration of obesity's role in occupational health and safety.. body-mass index| cardiovascular risk-factors| carpal-tunnel syndrome| diet-induced obesity| physical-activity| fat distribution| united-states| weight-gain| nutrition examination| parkinsons-disease.	MAR-2007	body-mass index| cardiovascular risk-factors| carpal-tunnel syndrome| diet-induced obesity| physical-activity| fat distribution| united-states| weight-gain| nutrition examination| parkinsons-disease	Schulte, PA; Wagner, GR; Ostry, A; Blanciforti, LA; Icutlip, RG; Krajnak, KM; Luster, M; Munson, AE; O'Callaghan, JP; Parks, CG; Simeonova, PP; Miller, DB	Work, obesity, and occupational safety and health		AMERICAN JOURNAL OF PUBLIC HEALTH		BODY-MASS INDEX; CARDIOVASCULAR RISK-FACTORS; CARPAL-TUNNEL SYNDROME; DIET-INDUCED OBESITY; PHYSICAL-ACTIVITY; FAT DISTRIBUTION; UNITED-STATES; WEIGHT-GAIN; NUTRITION EXAMINATION; PARKINSONS-DISEASE	There is increasing evidence that obesity and overweight may be related, in part, to adverse work conditions. In particular, the risk of obesity may increase in high-demand, low-control work environments, and for those who work long hours. In addition, obesity may modify the risk for vibration-induced injury and certain occupational musculoskeletal disorders. We hypothesized that obesity may also be a co-risk factor for the development of occupational asthma and cardiovascular disease that and it may modify the worker's response to occupational stress, immune response to chemical exposures, and risk of disease from occupational neurotoxins. We developed 5 conceptual models of the interrelationship of work, obesity, and occupational safety and health and highlighted the ethical, legal, and social issues related to fuller consideration of obesity's role in occupational health and safety.	147	90	2007	9	10.2105/AJPH.2006.086900	Public, Environmental & Occupational Health
Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3. GATA-3 plays a critical role in allergic diseases by regulating the release of cytokines from Th2 lymphocytes. However, the molecular mechanisms involved in the regulation of GATA-3 in human T lymphocytes are not yet understood. Using small interfering RNA to knock down GATA-3, we have demonstrated its critical role in regulating IL-4, IL-5, and IL-13 release from a human T cell line. Specific stimulation of T lymphocytes by costimulation of CD3 and CD28 to mimic activation by APCs induces translocation of GATA-3 from the cytoplasm to the nucleus, with binding to the promoter region of Th2 cytokine genes, as determined by chromatin immunoprecipitation. GATA-3 nuclear translocation is dependent on its phosphorylation on serine residues by p38 MAPK, which facilitates interaction with the nuclear transporter protein importin-a. This provides a means whereby allergen exposure leads to the expression of Th2 cytokines, and this novel mechanism may provide new approaches to treating allergic diseases.. activated protein-kinase| nuclear-localization sequence| cd4(+) t-cells| airway inflammation| signal integration| il-4 production| expression| asthma| lymphocytes| inhibition.	FEB 15-2007	activated protein-kinase| nuclear-localization sequence| cd4(+) t-cells| airway inflammation| signal integration| il-4 production| expression| asthma| lymphocytes| inhibition	Maneechotesuwan, K; Xin, Y; Ito, K; Jazrawi, E; Lee, KY; Usmani, OS; Barnes, PJ; Adcock, IM	Regulation of Th2 cytokine genes by p38 MAPK-mediated phosphorylation of GATA-3		JOURNAL OF IMMUNOLOGY		ACTIVATED PROTEIN-KINASE; NUCLEAR-LOCALIZATION SEQUENCE; CD4(+) T-CELLS; AIRWAY INFLAMMATION; SIGNAL INTEGRATION; IL-4 PRODUCTION; EXPRESSION; ASTHMA; LYMPHOCYTES; INHIBITION	GATA-3 plays a critical role in allergic diseases by regulating the release of cytokines from Th2 lymphocytes. However, the molecular mechanisms involved in the regulation of GATA-3 in human T lymphocytes are not yet understood. Using small interfering RNA to knock down GATA-3, we have demonstrated its critical role in regulating IL-4, IL-5, and IL-13 release from a human T cell line. Specific stimulation of T lymphocytes by costimulation of CD3 and CD28 to mimic activation by APCs induces translocation of GATA-3 from the cytoplasm to the nucleus, with binding to the promoter region of Th2 cytokine genes, as determined by chromatin immunoprecipitation. GATA-3 nuclear translocation is dependent on its phosphorylation on serine residues by p38 MAPK, which facilitates interaction with the nuclear transporter protein importin-a. This provides a means whereby allergen exposure leads to the expression of Th2 cytokines, and this novel mechanism may provide new approaches to treating allergic diseases.	44	90	2007	8		Immunology
Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice. Background Airborne particulate matter (PM) is an important factor associated with the enhanced prevalence of respiratory allergy. The PM adjuvant activity on allergic sensitization is a possible mechanism of action involved, and the induction of airway inflammation is suggested to be of importance in PM-induced adjuvant activity. Objective Because differently sized PM have different toxic potentials, we studied the role of particle size in the induction of airway inflammation and allergic sensitization. This was done using fine (0.250 and 0.260 mu m) and ultrafine (0.029 and 0.014 mu m) titanium dioxide (TiO2) and carbon black particles (CBP) with known differences in airway toxicity. Methods Mice were intranasally exposed to ovalbumin (OVA) alone or in combination with one of the different particles. The induction of airway inflammation and the immune adjuvant activity were studied in the lungs and lung-draining peribronchial lymph nodes (PBLN) at day 8. OVA-specific antibodies were measured at day 21, and the development of allergic airway inflammation was studied after OVA challenges (day 28). Results When administered at the same total particle mass (200 mu g), exposure to ultrafine TiO2 and CBP-induced airway inflammation, and had immune adjuvant activity. The latter was shown by increasing both the PBLN cell numbers and the production of OVA-specific T-helper type 2 (Th2) cytokines (IL-4, IL-5, IL-10 and IL-13). Whereas OVA-specific IgE and IgG1 levels in serum were only increased in animals exposed to the ultrafine TiO2, allergic airway inflammation could be detected in both ultrafine TiO2- and CBP-treated groups after challenges with OVA. Conclusion Our data show that only the ultrafine particles, with a small diameter and a large total surface area/mass, cause airway inflammation and have immune adjuvant activity in the current model supporting the hypothesis that particle toxicity is site-dependent and related to adjuvant activity.. adjuvant| airway| allergic| inflammation| intranasal| mouse| particulate matter| sensitization| ultrafine particles|diesel exhaust particles| carbon-black particles| adjuvant activity| pollen allergens| transition-metals| ambient particles| oxidative stress| dendritic cells| ige production| in-vitro.	NOV-2006	adjuvant| airway| allergic| inflammation| intranasal| mouse| particulate matter| sensitization| ultrafine particles|diesel exhaust particles| carbon-black particles| adjuvant activity| pollen allergens| transition-metals| ambient particles| oxidative stress| dendritic cells| ige production| in-vitro	de Haar, C; Hassing, I; Bol, M; Bleumink, R; Pieters, R	Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice		CLINICAL AND EXPERIMENTAL ALLERGY	adjuvant; airway; allergic; inflammation; intranasal; mouse; particulate matter; sensitization; ultrafine particles	DIESEL EXHAUST PARTICLES; CARBON-BLACK PARTICLES; ADJUVANT ACTIVITY; POLLEN ALLERGENS; TRANSITION-METALS; AMBIENT PARTICLES; OXIDATIVE STRESS; DENDRITIC CELLS; IGE PRODUCTION; IN-VITRO	Background Airborne particulate matter (PM) is an important factor associated with the enhanced prevalence of respiratory allergy. The PM adjuvant activity on allergic sensitization is a possible mechanism of action involved, and the induction of airway inflammation is suggested to be of importance in PM-induced adjuvant activity. Objective Because differently sized PM have different toxic potentials, we studied the role of particle size in the induction of airway inflammation and allergic sensitization. This was done using fine (0.250 and 0.260 mu m) and ultrafine (0.029 and 0.014 mu m) titanium dioxide (TiO2) and carbon black particles (CBP) with known differences in airway toxicity. Methods Mice were intranasally exposed to ovalbumin (OVA) alone or in combination with one of the different particles. The induction of airway inflammation and the immune adjuvant activity were studied in the lungs and lung-draining peribronchial lymph nodes (PBLN) at day 8. OVA-specific antibodies were measured at day 21, and the development of allergic airway inflammation was studied after OVA challenges (day 28). Results When administered at the same total particle mass (200 mu g), exposure to ultrafine TiO2 and CBP-induced airway inflammation, and had immune adjuvant activity. The latter was shown by increasing both the PBLN cell numbers and the production of OVA-specific T-helper type 2 (Th2) cytokines (IL-4, IL-5, IL-10 and IL-13). Whereas OVA-specific IgE and IgG1 levels in serum were only increased in animals exposed to the ultrafine TiO2, allergic airway inflammation could be detected in both ultrafine TiO2- and CBP-treated groups after challenges with OVA. Conclusion Our data show that only the ultrafine particles, with a small diameter and a large total surface area/mass, cause airway inflammation and have immune adjuvant activity in the current model supporting the hypothesis that particle toxicity is site-dependent and related to adjuvant activity.	50	90	2006	11	10.1111/j.1365-2222.2006.02586.x	Allergy; Immunology
Exhaled nitric oxide in the management of childhood asthma: A prospective 6-months study. Fractional exhaled nitric oxide (FeNO) is elevated in asthma and reflects eosinophilic airway inflammation. The aim of this prospective, randomized, single-blind study was to examine whether the inclusion of repeated FeNO measurements into asthma monitoring leads to an improvement in asthma outcome. Forty-seven children with mild to moderate asthma were allocated to a FeNO group (n = 22) and to a control group (n = 25). In the FeNO group therapy was based on symptoms, beta-agonist use, lung function, and FeNO whereas in the control group therapy was based on symptoms, beta-agonist use and lung function only Patients performed five visits in 6 weeks intervals. Frequency of respiratory symptoms, beta-agonist use, FEV1% predicted and the frequency of exacerbations were similar between groups. Patients in the FeNO group received higher doses of inhaled corticosteroids (ICS) (control group: median (interquartile range): 241 mu g (26-607 mu g); FeNo group: 316 mu g (200-500 mu g) and had significantly higher MEF,50% predicted (control group: median (interquartile range): 68.5% (55.8-83.1%); FeNO group: 83.2% (62.9%-98.3%). At a cut-off point of 22.9 ppb FeNO the best predictive value for exacerbations with a sensitivity of 80% and specificity of 60% was found. Significant relationships were observed between FeNO and dose of ICS (beta = 8.77; P < 0.002), beta-agonist use 2 weeks prior to a visit (beta = 0.11; P < 0.05), asthma symptoms (beta = 0.02; P < 0.0001), and bronchial hyperresponsiveness (beta = 0.04; P = 0.02). In conclusion, FeNO was related to important markers of asthma control. A therapy regimen aimed at lowering FeNO in children with asthma improved parameters of small airway function, but was not able to improve clinical markers of asthma control.. airway inflammation| childhood asthma| fractional exhaled nitric oxide| exhaled air| exacerbations| inhaled corticosteroids|dose-response relationship| children| healthy| reproducibility| recommendations| reduction| therapy| adults| air.	SEP-2006	airway inflammation| childhood asthma| fractional exhaled nitric oxide| exhaled air| exacerbations| inhaled corticosteroids|dose-response relationship| children| healthy| reproducibility| recommendations| reduction| therapy| adults| air	Fritsch, M; Uxa, S; Horak, F; Putschoegl, B; Dehlink, E; Szepfalusi, Z; Frischer, T	Exhaled nitric oxide in the management of childhood asthma: A prospective 6-months study		PEDIATRIC PULMONOLOGY	airway inflammation; childhood asthma; fractional exhaled nitric oxide; exhaled air; exacerbations; inhaled corticosteroids	DOSE-RESPONSE RELATIONSHIP; CHILDREN; HEALTHY; REPRODUCIBILITY; RECOMMENDATIONS; REDUCTION; THERAPY; ADULTS; AIR	Fractional exhaled nitric oxide (FeNO) is elevated in asthma and reflects eosinophilic airway inflammation. The aim of this prospective, randomized, single-blind study was to examine whether the inclusion of repeated FeNO measurements into asthma monitoring leads to an improvement in asthma outcome. Forty-seven children with mild to moderate asthma were allocated to a FeNO group (n = 22) and to a control group (n = 25). In the FeNO group therapy was based on symptoms, beta-agonist use, lung function, and FeNO whereas in the control group therapy was based on symptoms, beta-agonist use and lung function only Patients performed five visits in 6 weeks intervals. Frequency of respiratory symptoms, beta-agonist use, FEV1% predicted and the frequency of exacerbations were similar between groups. Patients in the FeNO group received higher doses of inhaled corticosteroids (ICS) (control group: median (interquartile range): 241 mu g (26-607 mu g); FeNo group: 316 mu g (200-500 mu g) and had significantly higher MEF,50% predicted (control group: median (interquartile range): 68.5% (55.8-83.1%); FeNO group: 83.2% (62.9%-98.3%). At a cut-off point of 22.9 ppb FeNO the best predictive value for exacerbations with a sensitivity of 80% and specificity of 60% was found. Significant relationships were observed between FeNO and dose of ICS (beta = 8.77; P < 0.002), beta-agonist use 2 weeks prior to a visit (beta = 0.11; P < 0.05), asthma symptoms (beta = 0.02; P < 0.0001), and bronchial hyperresponsiveness (beta = 0.04; P = 0.02). In conclusion, FeNO was related to important markers of asthma control. A therapy regimen aimed at lowering FeNO in children with asthma improved parameters of small airway function, but was not able to improve clinical markers of asthma control.	27	90	2006	8	10.1002/ppul.20455	Pediatrics; Respiratory System
IgE and IgG anti-house dust mite specificities in allergic disease. Background: There are few studies that quantitatively compare IgE and IgG antibody binding to the major and minor house dust mite allergens. Objective: To measure the IgE and IgG antibody specificities produced by adults and children, including children admitted to an emergency department for asthma. Methods: Antibodies were measured by solid-phase microliter assays. Results: Children recruited from the emergency department had similar titers and patterns of IgE antibody binding compared with children without acute disease. Der p 1 and 2 bound 50 % to 65 % of the IgE antibody, and most of the remaining binding was to Der p 4, 5, and 7. Der p 3, 8, 10, and 20 induced low titers. The pattern was similar across a wide range of antibouse.dust mite titers. IgG(1) and IgG(4) antibodies predominantly bound the major and midrange allergens and were mainly found in children with allergy. Children recruited in the emergency department had lower titers. Conclusion: The same IgE antibody-binding pattern and predominant contribution of Der p 1 and 2 was found across a wide range of total IgE antibody titers and for children admitted to an emergency department. IgG, and IgG(4) antibodies bound to the more allergenic specificities and were largely found in children with allergy. The IgG antibody titers were lower in sera from children admitted to the emergency department for asthma exacerbations. Clinical implications: Der p 1 and 2 and possibly Der p 4, 5, and 7 provide a formulation suitable for immunotherapy and diagnosis. Low IgG antibodies were a feature of acute disease.. house dust mite allergens| ige| igg(4)| igg(1)| asthma|modified th2 response| dermatophagoides-pteronyssinus| children| asthma| antibodies| extract| der-p-2| binding| population| childhood.	AUG-2006	house dust mite allergens| ige| igg(4)| igg(1)| asthma|modified th2 response| dermatophagoides-pteronyssinus| children| asthma| antibodies| extract| der-p-2| binding| population| childhood	Hales, BJ; Martin, AC; Pearce, LJ; Laing, IA; Hayden, CM; Goldblatt, J; Le Souef, PN; Thomas, WR	IgE and IgG anti-house dust mite specificities in allergic disease		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	house dust mite allergens; IgE; IgG(4); IgG(1); asthma	MODIFIED TH2 RESPONSE; DERMATOPHAGOIDES-PTERONYSSINUS; CHILDREN; ASTHMA; ANTIBODIES; EXTRACT; DER-P-2; BINDING; POPULATION; CHILDHOOD	Background: There are few studies that quantitatively compare IgE and IgG antibody binding to the major and minor house dust mite allergens. Objective: To measure the IgE and IgG antibody specificities produced by adults and children, including children admitted to an emergency department for asthma. Methods: Antibodies were measured by solid-phase microliter assays. Results: Children recruited from the emergency department had similar titers and patterns of IgE antibody binding compared with children without acute disease. Der p 1 and 2 bound 50 % to 65 % of the IgE antibody, and most of the remaining binding was to Der p 4, 5, and 7. Der p 3, 8, 10, and 20 induced low titers. The pattern was similar across a wide range of antibouse.dust mite titers. IgG(1) and IgG(4) antibodies predominantly bound the major and midrange allergens and were mainly found in children with allergy. Children recruited in the emergency department had lower titers. Conclusion: The same IgE antibody-binding pattern and predominant contribution of Der p 1 and 2 was found across a wide range of total IgE antibody titers and for children admitted to an emergency department. IgG, and IgG(4) antibodies bound to the more allergenic specificities and were largely found in children with allergy. The IgG antibody titers were lower in sera from children admitted to the emergency department for asthma exacerbations. Clinical implications: Der p 1 and 2 and possibly Der p 4, 5, and 7 provide a formulation suitable for immunotherapy and diagnosis. Low IgG antibodies were a feature of acute disease.	23	90	2006	7	10.1016/j.jaci.2006.04.001	Allergy; Immunology
Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitization to allergens. A GA(2)LEN project. The synthesis of allergen-specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen-specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen-specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen-specific IgE or IgG, epitope-specificity of IgE and their degree of polyclonality (mono- vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (Fc epsilon RI) and other factors regulating the activation of Fc epsilon RI-bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are many unanswered important questions that need to be addressed in order to better understand how IgE sensitization translates into clinical allergy. The assessment of differences between the asymptomatic and symptomatic groups of subjects represent one of the scientific programs of Global Allergy and Asthma European Network funded by the European Union and the hypotheses underlying these differences are presented in this paper.. allergy| asthma| basophil| ige| igg| rhinitis|fc-epsilon-ri| regulatory t-cells| house-dust mite| general-population sample| staphylococcus-aureus enterotoxins| human basophil releasability| mountain cedar pollinosis| birch pollen allergen| skin-test reactivity| total serum ige.	JUN-2006	allergy| asthma| basophil| ige| igg| rhinitis|fc-epsilon-ri| regulatory t-cells| house-dust mite| general-population sample| staphylococcus-aureus enterotoxins| human basophil releasability| mountain cedar pollinosis| birch pollen allergen| skin-test reactivity| total serum ige	Bousquet, J; Anto, JM; Bachert, C; Bousquet, PJ; Colombo, P; Crameri, R; Daeron, M; Fokkens, W; Leynaert, B; Lahoz, C; Maurer, M; Passalacqua, G; Valenta, R; van Hage, M; van Ree, R	Factors responsible for differences between asymptomatic subjects and patients presenting an IgE sensitization to allergens. A GA(2)LEN project		ALLERGY	allergy; asthma; basophil; IgE; IgG; rhinitis	FC-EPSILON-RI; REGULATORY T-CELLS; HOUSE-DUST MITE; GENERAL-POPULATION SAMPLE; STAPHYLOCOCCUS-AUREUS ENTEROTOXINS; HUMAN BASOPHIL RELEASABILITY; MOUNTAIN CEDAR POLLINOSIS; BIRCH POLLEN ALLERGEN; SKIN-TEST REACTIVITY; TOTAL SERUM IGE	The synthesis of allergen-specific IgE is required for the development of allergic diseases including allergic rhinitis and allergic asthma (patients), but many individuals with allergen-specific IgE do not develop symptoms (asymptomatic subjects). Differences may exist between asymptomatic subjects and patients. Whether the presence of allergen-specific IgE translates into clinical allergy most likely depends on a complex interplay of multiple factors. These include a family history of atopy, the levels of total serum IgE and, allergen-specific IgE or IgG, epitope-specificity of IgE and their degree of polyclonality (mono- vs polysensitized), as yet unidentified serum factors, the balance of T regulatory cells (Treg) and Th1/Th2 cells, the polymorphisms of the high affinity receptor for IgE (Fc epsilon RI) and other factors regulating the activation of Fc epsilon RI-bearing cells. Asymptomatic subjects may be more often monosensitized than patients who may be more often polysensitized. There are many unanswered important questions that need to be addressed in order to better understand how IgE sensitization translates into clinical allergy. The assessment of differences between the asymptomatic and symptomatic groups of subjects represent one of the scientific programs of Global Allergy and Asthma European Network funded by the European Union and the hypotheses underlying these differences are presented in this paper.	152	90	2006	10	10.1111/j.1398-9995.2006.01048.x	Allergy; Immunology
ATP-binding cassette (ABC) transporters in normal and pathological lung. ATP-binding cassette ( ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein ( P-gp), multidrug resistance-associated protein 1 ( MRP1) and breast cancer resistance protein ( BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e. g. air pollutants and cigarette smoke components, will be discussed as well as the ( mal) function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease ( COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases.. multidrug-resistance protein| transmembrane conductance regulator| p-glycoprotein expression| density-lipoprotein deficiency| bronchial epithelial-cells| organic anion transporter| cystic-fibrosis patients| dependent export pump| nitric-oxide synthase| blood-brain-barrier.	JUN 20-2005	multidrug-resistance protein| transmembrane conductance regulator| p-glycoprotein expression| density-lipoprotein deficiency| bronchial epithelial-cells| organic anion transporter| cystic-fibrosis patients| dependent export pump| nitric-oxide synthase| blood-brain-barrier	van der Deen, M; de Vries, EGE; Timens, W; Scheper, RJ; Timmer-Bosscha, H; Postma, DS	ATP-binding cassette (ABC) transporters in normal and pathological lung		RESPIRATORY RESEARCH		MULTIDRUG-RESISTANCE PROTEIN; TRANSMEMBRANE CONDUCTANCE REGULATOR; P-GLYCOPROTEIN EXPRESSION; DENSITY-LIPOPROTEIN DEFICIENCY; BRONCHIAL EPITHELIAL-CELLS; ORGANIC ANION TRANSPORTER; CYSTIC-FIBROSIS PATIENTS; DEPENDENT EXPORT PUMP; NITRIC-OXIDE SYNTHASE; BLOOD-BRAIN-BARRIER	ATP-binding cassette ( ABC) transporters are a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes in an energy-dependent manner. Many ABC transporters such as P-glycoprotein ( P-gp), multidrug resistance-associated protein 1 ( MRP1) and breast cancer resistance protein ( BCRP) are highly expressed in bronchial epithelium. This review aims to give new insights in the possible functions of ABC molecules in the lung in view of their expression in different cell types. Furthermore, their role in protection against noxious compounds, e. g. air pollutants and cigarette smoke components, will be discussed as well as the ( mal) function in normal and pathological lung. Several pulmonary drugs are substrates for ABC transporters and therefore, the delivery of these drugs to the site of action may be highly dependent on the presence and activity of many ABC transporters in several cell types. Three ABC transporters are known to play an important role in lung functioning. Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are responsible for respectively Tangier disease and fatal surfactant deficiency. The role of altered function of ABC transporters in highly prevalent pulmonary diseases such as asthma or chronic obstructive pulmonary disease ( COPD) have hardly been investigated so far. We especially focused on polymorphisms, knock-out mice models and in vitro results of pulmonary research. Insight in the function of ABC transporters in the lung may open new ways to facilitate treatment of lung diseases.	155	90	2005	16	10.1186/1465-9921-6-59	Respiratory System
Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study. Aims: The pulmonary outcome of extreme prematurity remains to be established in adults. We determined respiratory health and lung function status in a population-based, complete cohort of young preterms approaching adulthood. Methods. Forty-six preterms with gestational age less than or equal to28 wk or birthweight less than or equal to1000 g, born between 1982 and 1985, were compared to the temporally nearest term-born subject of equal gender. Spirometry, plethysmography, reversibility test to salbutamol and methacholine bronchial provocation test were performed. Neonatal data were obtained from hospital records and current symptoms from validated questionnaires. Results: When entering the study at a mean age of 17.7 (SD: 1.2) y, a doctor's diagnosis of asthma and use of asthma inhalers were significantly more prevalent among preterms than controls (one asthmatic control compared to nine preterms, all but one using asthma inhalers). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) were decreased and the discrepancies relative to controls increased parallel to increased severity of neonatal lung disease. Parameters of increased neonatal oxygen exposure significantly predicted FEV1. Adjusted for height, gender and age, FEV1 was reduced by a mean of 580 ml/s in subjects with a history of bronchopulmonary dysplasia. Fifty-six percent of preterms had a positive methacholine provocation test compared to 26% of controls. Conclusion: A substantially decreased FEV1, increased bronchial hyperresponsiveness and a number of established risk factors for steeper age-related decline in lung function were observed in preterms. A potential for early onset chronic obstructive pulmonary disease is present in subsets of this group.. infant| premature| bronchopulmonary dysplasia| lung diseases| obstructive| cohort studies|lung-function| bronchopulmonary dysplasia| respiratory health| weight| disease| responsiveness| sequelae| children| age| methacholine.	OCT-2004	infant| premature| bronchopulmonary dysplasia| lung diseases| obstructive| cohort studies|lung-function| bronchopulmonary dysplasia| respiratory health| weight| disease| responsiveness| sequelae| children| age| methacholine	Halvorsen, T; Skadberg, BT; Eide, GE; Roksund, OD; Carlsen, KH; Bakke, P	Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study		ACTA PAEDIATRICA	infant; premature; bronchopulmonary dysplasia; lung diseases; obstructive; cohort studies	LUNG-FUNCTION; BRONCHOPULMONARY DYSPLASIA; RESPIRATORY HEALTH; WEIGHT; DISEASE; RESPONSIVENESS; SEQUELAE; CHILDREN; AGE; METHACHOLINE	Aims: The pulmonary outcome of extreme prematurity remains to be established in adults. We determined respiratory health and lung function status in a population-based, complete cohort of young preterms approaching adulthood. Methods. Forty-six preterms with gestational age less than or equal to28 wk or birthweight less than or equal to1000 g, born between 1982 and 1985, were compared to the temporally nearest term-born subject of equal gender. Spirometry, plethysmography, reversibility test to salbutamol and methacholine bronchial provocation test were performed. Neonatal data were obtained from hospital records and current symptoms from validated questionnaires. Results: When entering the study at a mean age of 17.7 (SD: 1.2) y, a doctor's diagnosis of asthma and use of asthma inhalers were significantly more prevalent among preterms than controls (one asthmatic control compared to nine preterms, all but one using asthma inhalers). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV1) were decreased and the discrepancies relative to controls increased parallel to increased severity of neonatal lung disease. Parameters of increased neonatal oxygen exposure significantly predicted FEV1. Adjusted for height, gender and age, FEV1 was reduced by a mean of 580 ml/s in subjects with a history of bronchopulmonary dysplasia. Fifty-six percent of preterms had a positive methacholine provocation test compared to 26% of controls. Conclusion: A substantially decreased FEV1, increased bronchial hyperresponsiveness and a number of established risk factors for steeper age-related decline in lung function were observed in preterms. A potential for early onset chronic obstructive pulmonary disease is present in subsets of this group.	34	90	2004	7	10.1080/08035250410028101	Pediatrics
The effect of environmental tobacco smoke on eczema and allergic sensitization in children. Background The negative impact of environmental tobacco smoke (ETS) on airway diseases in children is well known. Whether there is an effect on atopic eczema is not clear. Objectives To determine the impact of ETS on atopic eczema, allergic sensitization and allergic airway diseases in 1669 school beginners. Methods The prevalence of atopy-related health outcomes was assessed by questionnaire, dermatological examination, skin prick testing and specific immunoglobulin E measurement. Exposure assessments were based on measurement of cotinine [expressed as cotinine to creatine ratio (CCR)] in spot urine samples (n = 1220) together with questionnaire and interview data on smoking behaviour of the parents. Results In the total study group, prevalence of atopic eczema diagnosed on examination was significantly associated with urinary CCR values. The odds ratio (OR) and 95% confidence interval (CI), calculated for an increase of 100 ng mg(-1) CCR was 1.97 (95% CI 1.23-3.16). The prevalence of skin manifestations according to questionnaire data as well as a history of asthma, wheezing, and hay fever were positively although not significantly associated with ETS exposure. When genetically predisposed children (defined by the presence of parental atopy) were compared with children whose parents had no atopy, the ORs of allergic outcome variables were generally higher in the first group. In the group of predisposed children, significant associations with urinary CCR were found for allergic sensitization against house dust mites as measured by skin prick test (OR 3.10, 95% CI 1.63-5.90). Conclusions Children are at a higher risk of developing an atopic eczema when exposed to ETS and genetically predisposed children are at higher risk of developing a sensitization against house dust mites.. eczema| parental atopy| predisposition| respiratory allergies| sensitization| tobacco smoke|parental smoking| passive-smoking| early-childhood| respiratory health| atopic-dermatitis| urinary cotinine| risk-factors| exposure| association| asthma.	JAN-2004	eczema| parental atopy| predisposition| respiratory allergies| sensitization| tobacco smoke|parental smoking| passive-smoking| early-childhood| respiratory health| atopic-dermatitis| urinary cotinine| risk-factors| exposure| association| asthma	Kramer, U; Lemmen, CH; Behrendt, H; Link, E; Schafer, T; Gostomzyk, J; Scherer, G; Ring, J	The effect of environmental tobacco smoke on eczema and allergic sensitization in children		BRITISH JOURNAL OF DERMATOLOGY	eczema; parental atopy; predisposition; respiratory allergies; sensitization; tobacco smoke	PARENTAL SMOKING; PASSIVE-SMOKING; EARLY-CHILDHOOD; RESPIRATORY HEALTH; ATOPIC-DERMATITIS; URINARY COTININE; RISK-FACTORS; EXPOSURE; ASSOCIATION; ASTHMA	Background The negative impact of environmental tobacco smoke (ETS) on airway diseases in children is well known. Whether there is an effect on atopic eczema is not clear. Objectives To determine the impact of ETS on atopic eczema, allergic sensitization and allergic airway diseases in 1669 school beginners. Methods The prevalence of atopy-related health outcomes was assessed by questionnaire, dermatological examination, skin prick testing and specific immunoglobulin E measurement. Exposure assessments were based on measurement of cotinine [expressed as cotinine to creatine ratio (CCR)] in spot urine samples (n = 1220) together with questionnaire and interview data on smoking behaviour of the parents. Results In the total study group, prevalence of atopic eczema diagnosed on examination was significantly associated with urinary CCR values. The odds ratio (OR) and 95% confidence interval (CI), calculated for an increase of 100 ng mg(-1) CCR was 1.97 (95% CI 1.23-3.16). The prevalence of skin manifestations according to questionnaire data as well as a history of asthma, wheezing, and hay fever were positively although not significantly associated with ETS exposure. When genetically predisposed children (defined by the presence of parental atopy) were compared with children whose parents had no atopy, the ORs of allergic outcome variables were generally higher in the first group. In the group of predisposed children, significant associations with urinary CCR were found for allergic sensitization against house dust mites as measured by skin prick test (OR 3.10, 95% CI 1.63-5.90). Conclusions Children are at a higher risk of developing an atopic eczema when exposed to ETS and genetically predisposed children are at higher risk of developing a sensitization against house dust mites.	33	90	2004	8	10.1111/j.1365-2133.2004.05710.x	Dermatology
Risk factors influencing the development of hand eczema in a population-based twin sample. Background A population-based twin study has recently shown that genetic factors are of significance for hand eczema. Objectives To characterize further a sample of this twin material with regard to contact allergy, atopic dermatitis and wet work. Methods In total, 1076 individual twins were examined clinically and patch tested. The diagnosis of atopic dermatitis was based on the U.K. Working Party criteria. The decision concerning wet work was based on the individual job description, taking into account the later introduced definition of at least 2 h of water exposure daily. The data were analysed by a newly developed statistical method which makes it possible to analyse the individual risk factor and at the same time discriminate between genetic and environmental factors. Results The statistical analysis confirmed atopic dermatitis as an important risk factor for hand eczema. Contact allergy was also confirmed as a significant risk factor for hand eczema, and the risk was related to strength (+ to + + +) of contact allergy. The results indicated that the high frequency of hand eczema in women in comparison with men was caused by environmental and not genetic factors. Aggregation of hand eczema within twin pairs was only to a minor degree explained by atopic dermatitis and nickel allergy (or other contact allergies). Conclusions We suggest that a hitherto unrecognized genetic risk factor for hand eczema independent of atopic dermatitis and contact allergy is probably of importance for the development of irritant contact dermatitis on the hands.. atopy| contact allergy| hand eczema| twins| wet work|contact-dermatitis| atopic-dermatitis| nickel allergy| sensitization| association| occupation| workers.	DEC-2003	atopy| contact allergy| hand eczema| twins| wet work|contact-dermatitis| atopic-dermatitis| nickel allergy| sensitization| association| occupation| workers	Bryld, LE; Hindsberger, C; Kyvik, KO; Agner, T; Menne, T	Risk factors influencing the development of hand eczema in a population-based twin sample		BRITISH JOURNAL OF DERMATOLOGY	atopy; contact allergy; hand eczema; twins; wet work	CONTACT-DERMATITIS; ATOPIC-DERMATITIS; NICKEL ALLERGY; SENSITIZATION; ASSOCIATION; OCCUPATION; WORKERS	Background A population-based twin study has recently shown that genetic factors are of significance for hand eczema. Objectives To characterize further a sample of this twin material with regard to contact allergy, atopic dermatitis and wet work. Methods In total, 1076 individual twins were examined clinically and patch tested. The diagnosis of atopic dermatitis was based on the U.K. Working Party criteria. The decision concerning wet work was based on the individual job description, taking into account the later introduced definition of at least 2 h of water exposure daily. The data were analysed by a newly developed statistical method which makes it possible to analyse the individual risk factor and at the same time discriminate between genetic and environmental factors. Results The statistical analysis confirmed atopic dermatitis as an important risk factor for hand eczema. Contact allergy was also confirmed as a significant risk factor for hand eczema, and the risk was related to strength (+ to + + +) of contact allergy. The results indicated that the high frequency of hand eczema in women in comparison with men was caused by environmental and not genetic factors. Aggregation of hand eczema within twin pairs was only to a minor degree explained by atopic dermatitis and nickel allergy (or other contact allergies). Conclusions We suggest that a hitherto unrecognized genetic risk factor for hand eczema independent of atopic dermatitis and contact allergy is probably of importance for the development of irritant contact dermatitis on the hands.	27	90	2003	7	10.1111/j.1365-2133.2003.05678.x	Dermatology
Are environmental factors important in primary systemic vasculitis? A case-control study. Objective. To investigate the association between primary systemic vasculitis (PSV) and environmental risk factors. Methods. Seventy-five PSV cases and 273 controls (220 nonvasculitis, 19 secondary vasculitis and 34 asthma controls) were interviewed using a structured questionnaire. Factors investigated were social class, occupational and residential history, smoking, pets, allergies, vaccinations, medications, hepatitis, tuberculosis, and farm exposure in the year before symptom onset (index year). The Standard Occupational Classification 2000 and job-exposure matrices were used to assess occupational silica, solvent, and metal exposure. Stepwise multiple logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) adjusted for potential confounders. Total PSV, subgroups (47 Wegener's granulomatosis [WG], 12 microscopic polyangiitis, 16 Churg-Strauss syndrome [CSS]), and antineutrophil cytoplasmic antibody (ANCA)-positive cases were compared with control groups. Results. Farming in the index year was significantly associated with PSV (OR 2.3 [95% CI 1.2-4.6]), with WG (2.7 [1.2-5.8]), with MPA (6.3 [1.9-21.6]), and with perinuclear ANCA (pANCA) (4.3 [1.5-12.7]). Farming during working lifetime was associated with PSV (2.2 [1.2-3.81) and with WG (2.7 [1.3-5.7]). Significant associations were found for high occupational silica exposure in the index year (with PSV 3.0 [1.0-8.4], with CSS 5.6 [1.3-23.5], and with ANCA 4.9 [1.3-18.6]), high occupational solvent exposure in the index year (with PSV 3.4 [0.9-12.5], with WG 4.8 [1.2-19.8], and with classic ANCA [cANCA] 3.9 [1.6-9.5]), high occupational solvent exposure during working lifetime (with PSV 2.7 [1.1-6.6], with WG 3.4 [1.3-8.9], and with cANCA 3.3 [1.0-10.8]), drug allergy (with PSV 3.6 [1.8-7.0], with WG 4.0 [1.8-8.7], and with cANCA 4.7 [1.9-11.7]), and allergy overall (with PSV 2.2 [1.2-3.9], with WG 2. 7 [1.4-5.7]). No other significant associations were found. Conclusion. A significant association between farming and PSV has been identified for the first time. Results also support previously reported associations with silica, solvents, and allergy.. churg-strauss-syndrome| rheumatology 1990 criteria| wegener granulomatosis| occupational exposure| hydrocarbon exposure| silica exposure| united-kingdom| disease| glomerulonephritis| antibodies.	MAR-2003	churg-strauss-syndrome| rheumatology 1990 criteria| wegener granulomatosis| occupational exposure| hydrocarbon exposure| silica exposure| united-kingdom| disease| glomerulonephritis| antibodies	Lane, SE; Watts, RA; Bentham, G; Innes, NJ; Scott, DGI	Are environmental factors important in primary systemic vasculitis? A case-control study		ARTHRITIS AND RHEUMATISM		CHURG-STRAUSS-SYNDROME; RHEUMATOLOGY 1990 CRITERIA; WEGENER GRANULOMATOSIS; OCCUPATIONAL EXPOSURE; HYDROCARBON EXPOSURE; SILICA EXPOSURE; UNITED-KINGDOM; DISEASE; GLOMERULONEPHRITIS; ANTIBODIES	Objective. To investigate the association between primary systemic vasculitis (PSV) and environmental risk factors. Methods. Seventy-five PSV cases and 273 controls (220 nonvasculitis, 19 secondary vasculitis and 34 asthma controls) were interviewed using a structured questionnaire. Factors investigated were social class, occupational and residential history, smoking, pets, allergies, vaccinations, medications, hepatitis, tuberculosis, and farm exposure in the year before symptom onset (index year). The Standard Occupational Classification 2000 and job-exposure matrices were used to assess occupational silica, solvent, and metal exposure. Stepwise multiple logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) adjusted for potential confounders. Total PSV, subgroups (47 Wegener's granulomatosis [WG], 12 microscopic polyangiitis, 16 Churg-Strauss syndrome [CSS]), and antineutrophil cytoplasmic antibody (ANCA)-positive cases were compared with control groups. Results. Farming in the index year was significantly associated with PSV (OR 2.3 [95% CI 1.2-4.6]), with WG (2.7 [1.2-5.8]), with MPA (6.3 [1.9-21.6]), and with perinuclear ANCA (pANCA) (4.3 [1.5-12.7]). Farming during working lifetime was associated with PSV (2.2 [1.2-3.81) and with WG (2.7 [1.3-5.7]). Significant associations were found for high occupational silica exposure in the index year (with PSV 3.0 [1.0-8.4], with CSS 5.6 [1.3-23.5], and with ANCA 4.9 [1.3-18.6]), high occupational solvent exposure in the index year (with PSV 3.4 [0.9-12.5], with WG 4.8 [1.2-19.8], and with classic ANCA [cANCA] 3.9 [1.6-9.5]), high occupational solvent exposure during working lifetime (with PSV 2.7 [1.1-6.6], with WG 3.4 [1.3-8.9], and with cANCA 3.3 [1.0-10.8]), drug allergy (with PSV 3.6 [1.8-7.0], with WG 4.0 [1.8-8.7], and with cANCA 4.7 [1.9-11.7]), and allergy overall (with PSV 2.2 [1.2-3.9], with WG 2. 7 [1.4-5.7]). No other significant associations were found. Conclusion. A significant association between farming and PSV has been identified for the first time. Results also support previously reported associations with silica, solvents, and allergy.	40	90	2003	10	10.1002/art.10830	Rheumatology
Hygiene hypothesis: Fact or fiction?. The hygiene hypothesis of asthma and allergy has recently received a swell of popularity and published supporting evidence, and has been extended to autoimmune conditions of childhood. Broadly stated, naturally occurring infections and microbial exposures might essentially immunize against the development of asthma and allergic and autoimmune diseases. If true, then reductions in nature's immunotherapy over the past century might be a major factor in the global increase of these conditions (eg, the higher prevalence of asthma and allergies in urban metropolitan areas compared with rural and farm communities) and might lead to new therapies for these conditions. Although such a unifying hypothesis has great appeal, currently it is only speculation about what might be at the end of the investigative road. How close are the current studies to establishing a causal relationship between microbial exposures and a reduction in allergic, asthmatic, and autoimmune disease prevalence? A systematic epidemiologic appraisal of the current hygiene hypothesis evidence can provide a critical analysis of what is currently known and an investigative blueprint for future studies that can ultimately prove causation and improve recommendations, interventions, and therapies. (J Allergy Clin Immunol 2003;111:471-8.).. hygiene| allergy| atopy| asthma| autoimmunity| childhood| endotoxin| epidemiology type 1diabetes| celiac disease| inflammatory bowel disease| rheumatoid arthritis| microbiology|house-dust endotoxin| day-care attendance| atopic disease| childhood asthma| united-states| school-age| early-life| exposure| children| risk.	MAR-2003	hygiene| allergy| atopy| asthma| autoimmunity| childhood| endotoxin| epidemiology type 1diabetes| celiac disease| inflammatory bowel disease| rheumatoid arthritis| microbiology|house-dust endotoxin| day-care attendance| atopic disease| childhood asthma| united-states| school-age| early-life| exposure| children| risk	Liu, AH; Murphy, JR	Hygiene hypothesis: Fact or fiction?		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	hygiene; allergy; atopy; asthma; autoimmunity; childhood; endotoxin; epidemiology type 1diabetes; celiac disease; inflammatory bowel disease; rheumatoid arthritis; microbiology	HOUSE-DUST ENDOTOXIN; DAY-CARE ATTENDANCE; ATOPIC DISEASE; CHILDHOOD ASTHMA; UNITED-STATES; SCHOOL-AGE; EARLY-LIFE; EXPOSURE; CHILDREN; RISK	The hygiene hypothesis of asthma and allergy has recently received a swell of popularity and published supporting evidence, and has been extended to autoimmune conditions of childhood. Broadly stated, naturally occurring infections and microbial exposures might essentially immunize against the development of asthma and allergic and autoimmune diseases. If true, then reductions in nature's immunotherapy over the past century might be a major factor in the global increase of these conditions (eg, the higher prevalence of asthma and allergies in urban metropolitan areas compared with rural and farm communities) and might lead to new therapies for these conditions. Although such a unifying hypothesis has great appeal, currently it is only speculation about what might be at the end of the investigative road. How close are the current studies to establishing a causal relationship between microbial exposures and a reduction in allergic, asthmatic, and autoimmune disease prevalence? A systematic epidemiologic appraisal of the current hygiene hypothesis evidence can provide a critical analysis of what is currently known and an investigative blueprint for future studies that can ultimately prove causation and improve recommendations, interventions, and therapies. (J Allergy Clin Immunol 2003;111:471-8.).	41	90	2003	8	10.1067/mai.2003.172	Allergy; Immunology
Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort. Background Multiple genetic studies have shown linkage of atopy-related phenotypes to chromosome 5q31. In this region several candidate genes for atopy are localized such as the Th2 cytokines IL-4, IL-5 and IL-13, but also CD14, a receptor for LPS. Recently, a functional CD14 promoter polymorphism was related to total and specific IgE responsiveness. Objective The aim of our study was to evaluate the role of this single nucleotide polymorphism (SNP) in a large German birth cohort. Methods Atopy-related phenotypes were longitudinally carefully evaluated in over 800 children from birth to the age of 10 years. Yearly visits included standardized interviews, physical examinations and determination of total and specific IgE antibodies. Pulmonary function tests and histamine provocations were performed at the age of seven. Eight-hundred and seventy-two children of the Multicenter Allergy Study (MAS) cohort were genotyped using melting curve and restriction digest analyses. Results CD14-159 allele frequencies were consistent with previous reports, however, no association of the SNP with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels could be observed. Conclusion The CD14-159 SNP might not play a major role in the development of atopy in German children.. atopy| cd14| genetics| ige|endotoxin| exposure| asthma| atopy| gene.	FEB-2003	atopy| cd14| genetics| ige|endotoxin| exposure| asthma| atopy| gene	Sengler, C; Haider, A; Sommerfeld, C; Lau, S; Baldini, M; Martinez, F; Wahn, U; Nickel, R	Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort		CLINICAL AND EXPERIMENTAL ALLERGY	atopy; CD14; genetics; IgE	ENDOTOXIN; EXPOSURE; ASTHMA; ATOPY; GENE	Background Multiple genetic studies have shown linkage of atopy-related phenotypes to chromosome 5q31. In this region several candidate genes for atopy are localized such as the Th2 cytokines IL-4, IL-5 and IL-13, but also CD14, a receptor for LPS. Recently, a functional CD14 promoter polymorphism was related to total and specific IgE responsiveness. Objective The aim of our study was to evaluate the role of this single nucleotide polymorphism (SNP) in a large German birth cohort. Methods Atopy-related phenotypes were longitudinally carefully evaluated in over 800 children from birth to the age of 10 years. Yearly visits included standardized interviews, physical examinations and determination of total and specific IgE antibodies. Pulmonary function tests and histamine provocations were performed at the age of seven. Eight-hundred and seventy-two children of the Multicenter Allergy Study (MAS) cohort were genotyped using melting curve and restriction digest analyses. Results CD14-159 allele frequencies were consistent with previous reports, however, no association of the SNP with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels could be observed. Conclusion The CD14-159 SNP might not play a major role in the development of atopy in German children.	13	90	2003	4	10.1046/j.1365-2222.2003.01549.x	Allergy; Immunology
Asthma in the United States: Burden and current theories. Asthma has emerged as a major public health problem in the United States over the past 20 years. Currently, nearly 15 million Americans have asthma, including almost 5 million children. The number of asthma cases has more than doubled since 1980. Approximately 5,500 persons die from asthma each year, and rates have increased over the past 20 years. Rates of death, hospitalization, and emergency department visits are 2-3 times higher among African Americans than among white Americans. The costs of asthma have also increased to $12.7 billion in 1998. Both lifestyle and environmental hypotheses have been invoked to explain the increase in asthma prevalence. Several studies have examined the relationship of obesity and asthma and found associations suggesting that obesity predisposes to the development of asthma. Some studies have found that day care attendance and having older siblings protect against the development of asthma. This observation has led investigators to hypothesize that increased exposure to microbial agents might protect against asthma (the hygiene hypothesis). Environmental exposures found to predispose to asthma include house dust mite allergen and environmental tobacco smoke. Although current knowledge does not permit definitive conclusions about the causes of asthma onset, better adherence to current recommendations for medical therapy and environmental management of asthma would reduce the burden of this disease.. asthma| epidemiology| hygiene| incidence| indoor environment| obesity|body-mass index| family-size| weight| childhood| adults| risk.	AUG-2002	asthma| epidemiology| hygiene| incidence| indoor environment| obesity|body-mass index| family-size| weight| childhood| adults| risk	Redd, SC	Asthma in the United States: Burden and current theories		ENVIRONMENTAL HEALTH PERSPECTIVES	asthma; epidemiology; hygiene; incidence; indoor environment; obesity	BODY-MASS INDEX; FAMILY-SIZE; WEIGHT; CHILDHOOD; ADULTS; RISK	Asthma has emerged as a major public health problem in the United States over the past 20 years. Currently, nearly 15 million Americans have asthma, including almost 5 million children. The number of asthma cases has more than doubled since 1980. Approximately 5,500 persons die from asthma each year, and rates have increased over the past 20 years. Rates of death, hospitalization, and emergency department visits are 2-3 times higher among African Americans than among white Americans. The costs of asthma have also increased to $12.7 billion in 1998. Both lifestyle and environmental hypotheses have been invoked to explain the increase in asthma prevalence. Several studies have examined the relationship of obesity and asthma and found associations suggesting that obesity predisposes to the development of asthma. Some studies have found that day care attendance and having older siblings protect against the development of asthma. This observation has led investigators to hypothesize that increased exposure to microbial agents might protect against asthma (the hygiene hypothesis). Environmental exposures found to predispose to asthma include house dust mite allergen and environmental tobacco smoke. Although current knowledge does not permit definitive conclusions about the causes of asthma onset, better adherence to current recommendations for medical therapy and environmental management of asthma would reduce the burden of this disease.	28	90	2002	4		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Bronchial responsiveness to adenosine 5 '-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV. Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and BHR to methacholine and AMP in a population of young adults, with mild symptoms if any, was evaluated. A total of 230 subjects who participated in a follow-up study on occupational allergy were included. Before exposure to occupational allergens, subjects completed a questionnaire on respiratory symptoms and were tested for atopy, blood eosinophilia (greater than or equal to 275/mm(3)), and BHR to methacholine and AMP (greater than or equal to 15% fall in FEV1). Risk estimates were expressed as prevalence ratios (PR) and 95% confidence intervals (95% CI). Dose-response slopes (DRS) for methacholine and AMP were compared between healthy control subjects, self-reported allergic rhinitis, and allergic asthma. BHR to AMP was associated with allergic rhinitis (PR 2.51, 95% Cl: 1.22;5.17), allergic asthma (PR 4.38, 95% Cl: 1.98;9.66), with atopy (PR 3.87, 95% Cl: 1.76;8.52), and blood eosinophilia (PR 3.57, 95% Cl: 1.48;8.77), but not with baseline FEV1. BHR to methacholine was inversely related to prechallenge FEV1 (PR 0.97, 95% Cl: 0.96;0.99). For both methacholine and AMP the geometric mean DRS increased along the axis asymptomatic-allergic rhinitis-allergic asthma, but for AMP the increase was the strongest. In this population study among young adults, BHR to AMP refers to allergic background of airway lability and BHR to methacholine is related to a diminished airway caliber.. adenosine| bronchial hyperresponsiveness| methacholine| airway allergy|nitric-oxide levels| asthma| hyperresponsiveness| inflammation| rhinitis| markers| nonasthmatics| eosinophils| prevalence| population.	FEB 1-2002	adenosine| bronchial hyperresponsiveness| methacholine| airway allergy|nitric-oxide levels| asthma| hyperresponsiveness| inflammation| rhinitis| markers| nonasthmatics| eosinophils| prevalence| population	De Meer, G; Heederik, D; Postma, DS	Bronchial responsiveness to adenosine 5 '-monophosphate (AMP) and methacholine differ in their relationship with airway allergy and baseline FEV		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	adenosine; bronchial hyperresponsiveness; methacholine; airway allergy	NITRIC-OXIDE LEVELS; ASTHMA; HYPERRESPONSIVENESS; INFLAMMATION; RHINITIS; MARKERS; NONASTHMATICS; EOSINOPHILS; PREVALENCE; POPULATION	Bronchial hyperresponsiveness (BHR) and inflammation are central hallmarks of asthma. Studies in patients with asthma suggest that BHR to adenosine 5'-monophosphate (AMP) is a better marker of bronchial inflammation than BHR to methacholine. The association between markers of airway inflammation and BHR to methacholine and AMP in a population of young adults, with mild symptoms if any, was evaluated. A total of 230 subjects who participated in a follow-up study on occupational allergy were included. Before exposure to occupational allergens, subjects completed a questionnaire on respiratory symptoms and were tested for atopy, blood eosinophilia (greater than or equal to 275/mm(3)), and BHR to methacholine and AMP (greater than or equal to 15% fall in FEV1). Risk estimates were expressed as prevalence ratios (PR) and 95% confidence intervals (95% CI). Dose-response slopes (DRS) for methacholine and AMP were compared between healthy control subjects, self-reported allergic rhinitis, and allergic asthma. BHR to AMP was associated with allergic rhinitis (PR 2.51, 95% Cl: 1.22;5.17), allergic asthma (PR 4.38, 95% Cl: 1.98;9.66), with atopy (PR 3.87, 95% Cl: 1.76;8.52), and blood eosinophilia (PR 3.57, 95% Cl: 1.48;8.77), but not with baseline FEV1. BHR to methacholine was inversely related to prechallenge FEV1 (PR 0.97, 95% Cl: 0.96;0.99). For both methacholine and AMP the geometric mean DRS increased along the axis asymptomatic-allergic rhinitis-allergic asthma, but for AMP the increase was the strongest. In this population study among young adults, BHR to AMP refers to allergic background of airway lability and BHR to methacholine is related to a diminished airway caliber.	25	90	2002	5		General & Internal Medicine; Respiratory System
Will genetically modified foods be allergenic?. Foods produced through agricultural biotechnology, including such staples as corn, soybeans, canola, and potatoes, are already reaching the consumer marketplace. Agricultural biotechnology offers the promise to produce crops with improved agronomic characteristics (eg, insect resistance, herbicide tolerance, disease resistance, and climatic tolerance) and enhanced consumer benefits (eg, better taste and texture, longer shelf life, and more nutritious). Certainly, the products of agricultural biotechnology should be subjected to a careful and complete safety assessment before commercialization. Because the genetic modification ultimately results in the introduction of new proteins into the food plant, the safety, including the potential allergenicity, of the newly introduced proteins must be assessed. Although most allergens are proteins, only a few of the many proteins found in foods are allergenic under the typical circumstances of exposure. The potential allergenicity of the introduced proteins call be evaluated by focusing on the source of the gene, the sequence homology of the newly introduced protein to known allergens, the expression level of the novel protein in the modified crop, the functional classification of the novel protein, the reactivity of the novel protein with IgE from the serum of individuals with known allergies to the source of the transferred genetic material, and various physicochemical properties of the newly introduced protein, such as heat stability and digestive stability. Few products of agricultural biotechnology (and none of the current products) will involve the transfer of genes from known allergenic sources, Applying such criteria provides reasonable assurance that the newly introduced protein has limited capability to become an allergen.. biotechnology| allergy| food| sequence homology| digestion| exposure| classification| heat stability|breast-fed infants| cows milk allergy| beta-lactoglobulin| hypersensitivity reactions| bacillus-thuringiensis| peanut protein| double-blind| in-vitro| children| identification.	MAY-2001	biotechnology| allergy| food| sequence homology| digestion| exposure| classification| heat stability|breast-fed infants| cows milk allergy| beta-lactoglobulin| hypersensitivity reactions| bacillus-thuringiensis| peanut protein| double-blind| in-vitro| children| identification	Taylor, SL; Hefle, SL	Will genetically modified foods be allergenic?		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	biotechnology; allergy; food; sequence homology; digestion; exposure; classification; heat stability	BREAST-FED INFANTS; COWS MILK ALLERGY; BETA-LACTOGLOBULIN; HYPERSENSITIVITY REACTIONS; BACILLUS-THURINGIENSIS; PEANUT PROTEIN; DOUBLE-BLIND; IN-VITRO; CHILDREN; IDENTIFICATION	Foods produced through agricultural biotechnology, including such staples as corn, soybeans, canola, and potatoes, are already reaching the consumer marketplace. Agricultural biotechnology offers the promise to produce crops with improved agronomic characteristics (eg, insect resistance, herbicide tolerance, disease resistance, and climatic tolerance) and enhanced consumer benefits (eg, better taste and texture, longer shelf life, and more nutritious). Certainly, the products of agricultural biotechnology should be subjected to a careful and complete safety assessment before commercialization. Because the genetic modification ultimately results in the introduction of new proteins into the food plant, the safety, including the potential allergenicity, of the newly introduced proteins must be assessed. Although most allergens are proteins, only a few of the many proteins found in foods are allergenic under the typical circumstances of exposure. The potential allergenicity of the introduced proteins call be evaluated by focusing on the source of the gene, the sequence homology of the newly introduced protein to known allergens, the expression level of the novel protein in the modified crop, the functional classification of the novel protein, the reactivity of the novel protein with IgE from the serum of individuals with known allergies to the source of the transferred genetic material, and various physicochemical properties of the newly introduced protein, such as heat stability and digestive stability. Few products of agricultural biotechnology (and none of the current products) will involve the transfer of genes from known allergenic sources, Applying such criteria provides reasonable assurance that the newly introduced protein has limited capability to become an allergen.	43	90	2001	7		Allergy; Immunology
CLA reduces antigen-induced histamine and PGE(2) release from sensitized guinea pig tracheae. Conjugated linoleic acid (CLA) has been shown to enhance immune reactions such as lymphocyte blastogenesis and delayed-type hypersensitivity. We investigated the role of CLA in type I (immediate) hypersensitivity, using a guinea pig tracheal superfusion model for measuring antigen-induced airway smooth muscle contraction and inflammatory mediator release. Female Hartley guinea pigs were fed a diet supplemented with 0.25 g corn oil or linoleic acid/100 g of diet (control) or 0.25 g CLA/100 g of diet for at least 1 wk before and during active sensitization to ovalbumin antigen. Tracheae from sensitized guinea pigs were suspended in air-filled water-jacketed (37 degrees C) tissue chambers in a superfusion apparatus. Tracheae were superfused with buffer containing antigen, and tissue contraction was recorded. Superfusate was collected at 90-s intervals for evaluation of histamine and PGE(2) release. CLA did not affect antigen-induced tracheal contractions when expressed as gram contraction per gram tissue. CLA significantly reduced antigen-induced histamine and PGE(2) release. CLA appears to decrease release of some inflammatory mediators during type I hypersensitivity reactions.. type i hypersensitivity| conjugated linoleic acid| immunity| allergies| asthma|conjugated linoleic-acid| 3t3-l1 preadipocytes| body-composition| fatty-acids| lymphocyte| modulation| growth| rats| mice| proliferation.	MAR-2001	type i hypersensitivity| conjugated linoleic acid| immunity| allergies| asthma|conjugated linoleic-acid| 3t3-l1 preadipocytes| body-composition| fatty-acids| lymphocyte| modulation| growth| rats| mice| proliferation	Whigham, LD; Cook, EB; Stahl, JL; Saban, R; Bjorling, DE; Pariza, MW; Cook, ME	CLA reduces antigen-induced histamine and PGE(2) release from sensitized guinea pig tracheae		AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY	type I hypersensitivity; conjugated linoleic acid; immunity; allergies; asthma	CONJUGATED LINOLEIC-ACID; 3T3-L1 PREADIPOCYTES; BODY-COMPOSITION; FATTY-ACIDS; LYMPHOCYTE; MODULATION; GROWTH; RATS; MICE; PROLIFERATION	Conjugated linoleic acid (CLA) has been shown to enhance immune reactions such as lymphocyte blastogenesis and delayed-type hypersensitivity. We investigated the role of CLA in type I (immediate) hypersensitivity, using a guinea pig tracheal superfusion model for measuring antigen-induced airway smooth muscle contraction and inflammatory mediator release. Female Hartley guinea pigs were fed a diet supplemented with 0.25 g corn oil or linoleic acid/100 g of diet (control) or 0.25 g CLA/100 g of diet for at least 1 wk before and during active sensitization to ovalbumin antigen. Tracheae from sensitized guinea pigs were suspended in air-filled water-jacketed (37 degrees C) tissue chambers in a superfusion apparatus. Tracheae were superfused with buffer containing antigen, and tissue contraction was recorded. Superfusate was collected at 90-s intervals for evaluation of histamine and PGE(2) release. CLA did not affect antigen-induced tracheal contractions when expressed as gram contraction per gram tissue. CLA significantly reduced antigen-induced histamine and PGE(2) release. CLA appears to decrease release of some inflammatory mediators during type I hypersensitivity reactions.	33	90	2001	5		Physiology
Previous pulmonary diseases and risk of lung cancer in Gansu Province, China. Backgrounds Although active smoking is well established as the main cause of lung cancer, there is accumulating evidence that history of prior lung diseases may be an independent risk factor for lung cancer. Methods A population-based case-control study in Gansu Province, China identified 886 lung cancer cases (656 male, 230 female) diagnosed between January 1994 and April 1998. A standardized interview collected information on a variety of potential risk factors including a history of physician-diagnosed non-malignant lung diseases (pulmonary tuberculosis, chronic bronchitis/emphysema, asthma, pneumonia), age and year in which each condition was first diagnosed, and any therapy or hospitalization received. Results Pulmonary tuberculosis (odds ratio [OR] = 2.1, 95% CI:1.4-3.1) and chronic bronchitis/emphysema (OR = 1.4 95% CI : 1.1-1.8) were associated with increased risk of lung cancer, after adjustment for active smoking and socioeconomic status. The OR for asthma (OR = 1.4, 95% CI : 0.9-2.1) and pneumonia (OR = 1.5, 95% CI: 1.0-2.3) were also elevated. The risk of lung cancer remained significant for pulmonary tuberculosis and chronic bronchitis/emphysema when analysis was limited to the pathologically confirmed cases and self-responders. Conclusions This study provides additional evidence that previous pulmonary tuberculosis and chronic bronchitis/emphysema are causally related to lung cancer, although the precise mechanism is still unclear. The results for asthma and pneumonia, while suggestive of a positive association, did not reach the traditional level of statistical significance and should be interpreted with caution.. case-control studies| lung neoplasms| tuberculosis| pulmonary| bronchitis| pulmonary emphysema| asthma| pneumonia|nonsmoking women| family history| tuberculosis patients| respiratory-disease| mortality| smoking| cohort| exposure| asthma| miners.	FEB-2001	case-control studies| lung neoplasms| tuberculosis| pulmonary| bronchitis| pulmonary emphysema| asthma| pneumonia|nonsmoking women| family history| tuberculosis patients| respiratory-disease| mortality| smoking| cohort| exposure| asthma| miners	Brenner, AV; Wang, ZY; Kleinerman, RA; Wang, LD; Zhang, SZ; Metayer, C; Chen, K; Lei, SW; Cui, HX; Lubin, JH	Previous pulmonary diseases and risk of lung cancer in Gansu Province, China		INTERNATIONAL JOURNAL OF EPIDEMIOLOGY	case-control studies; lung neoplasms; tuberculosis; pulmonary; bronchitis; pulmonary emphysema; asthma; pneumonia	NONSMOKING WOMEN; FAMILY HISTORY; TUBERCULOSIS PATIENTS; RESPIRATORY-DISEASE; MORTALITY; SMOKING; COHORT; EXPOSURE; ASTHMA; MINERS	Backgrounds Although active smoking is well established as the main cause of lung cancer, there is accumulating evidence that history of prior lung diseases may be an independent risk factor for lung cancer. Methods A population-based case-control study in Gansu Province, China identified 886 lung cancer cases (656 male, 230 female) diagnosed between January 1994 and April 1998. A standardized interview collected information on a variety of potential risk factors including a history of physician-diagnosed non-malignant lung diseases (pulmonary tuberculosis, chronic bronchitis/emphysema, asthma, pneumonia), age and year in which each condition was first diagnosed, and any therapy or hospitalization received. Results Pulmonary tuberculosis (odds ratio [OR] = 2.1, 95% CI:1.4-3.1) and chronic bronchitis/emphysema (OR = 1.4 95% CI : 1.1-1.8) were associated with increased risk of lung cancer, after adjustment for active smoking and socioeconomic status. The OR for asthma (OR = 1.4, 95% CI : 0.9-2.1) and pneumonia (OR = 1.5, 95% CI: 1.0-2.3) were also elevated. The risk of lung cancer remained significant for pulmonary tuberculosis and chronic bronchitis/emphysema when analysis was limited to the pathologically confirmed cases and self-responders. Conclusions This study provides additional evidence that previous pulmonary tuberculosis and chronic bronchitis/emphysema are causally related to lung cancer, although the precise mechanism is still unclear. The results for asthma and pneumonia, while suggestive of a positive association, did not reach the traditional level of statistical significance and should be interpreted with caution.	38	90	2001	7	10.1093/ije/30.1.118	Public, Environmental & Occupational Health
Purification, biochemical, and immunological characterisation of a major food allergen: different immunoglobulin E recognition of the apo- and calcium-bound forms of carp parvalbumin. Background-Almost 4% of the population suffer from food allergy which is an adverse reaction to food with an underlying immunological mechanism. Aims-To characterise one of the most frequent IgE defined food allergens, fish parvalbumin. Methods-Tissue and subcellular distribution of carp parvalbumin was analysed by immunogold electron microscopy and cell fractionation. Parvalbumin was purified to homogeneity, analysed by mass spectrometry and circular dichroism (CD) spectroscopy, and its allergenic activity was analysed by IgE binding and basophil histamine release tests. Results-The isoelectric point (pI) 4.7 form of carp parvalbumin, a three EF-hand calcium-binding protein, was purified to homogeneity. CD analysis revealed a remarkable stability and refolding capacity of calcium-bound parvalbumin. This may explain why parvalbumin, despite cooking and exposure to the gastrointestinal tract, can sensitise patients. Purified parvalbumin reacted with IgE of more than 95% of individuals allergic to fish, induced dose-dependent basophil histamine release and contained, on average, 83% of the IgE epitopes present in other fish species. Calcium depletion reduced the IgE binding capacity of parvalbumin which, according to CD analysis, may be due to conformation-dependent IgE recognition. Conclusions-Purified carp parvalbumin represents an important cross reactive food allergen. It can be used for in vitro and in vivo diagnosis of fish-induced food allergy. Our finding that the ape-form of parvalbumin had a greatly reduced IgE binding capacity indicates that this form may be a candidate for safe immunotherapy of fish-related food allergy.. food allergy| parvalbumin| circular dichroism| epitopes| antibodies| immunochemistry|binding protein parvalbumin| birch pollen allergen| fish hypersensitivity| muscular parvalbumins| adverse reactions| ige-binding| muscle| sites| expression| challenge.	MAY-2000	food allergy| parvalbumin| circular dichroism| epitopes| antibodies| immunochemistry|binding protein parvalbumin| birch pollen allergen| fish hypersensitivity| muscular parvalbumins| adverse reactions| ige-binding| muscle| sites| expression| challenge	Bugajska-Schretter, A; Grote, M; Vangelista, L; Valent, P; Sperr, WR; Rumpold, H; Pastore, A; Reichelt, R; Valenta, R; Spitzauer, S	Purification, biochemical, and immunological characterisation of a major food allergen: different immunoglobulin E recognition of the apo- and calcium-bound forms of carp parvalbumin		GUT	food allergy; parvalbumin; circular dichroism; epitopes; antibodies; immunochemistry	BINDING PROTEIN PARVALBUMIN; BIRCH POLLEN ALLERGEN; FISH HYPERSENSITIVITY; MUSCULAR PARVALBUMINS; ADVERSE REACTIONS; IGE-BINDING; MUSCLE; SITES; EXPRESSION; CHALLENGE	Background-Almost 4% of the population suffer from food allergy which is an adverse reaction to food with an underlying immunological mechanism. Aims-To characterise one of the most frequent IgE defined food allergens, fish parvalbumin. Methods-Tissue and subcellular distribution of carp parvalbumin was analysed by immunogold electron microscopy and cell fractionation. Parvalbumin was purified to homogeneity, analysed by mass spectrometry and circular dichroism (CD) spectroscopy, and its allergenic activity was analysed by IgE binding and basophil histamine release tests. Results-The isoelectric point (pI) 4.7 form of carp parvalbumin, a three EF-hand calcium-binding protein, was purified to homogeneity. CD analysis revealed a remarkable stability and refolding capacity of calcium-bound parvalbumin. This may explain why parvalbumin, despite cooking and exposure to the gastrointestinal tract, can sensitise patients. Purified parvalbumin reacted with IgE of more than 95% of individuals allergic to fish, induced dose-dependent basophil histamine release and contained, on average, 83% of the IgE epitopes present in other fish species. Calcium depletion reduced the IgE binding capacity of parvalbumin which, according to CD analysis, may be due to conformation-dependent IgE recognition. Conclusions-Purified carp parvalbumin represents an important cross reactive food allergen. It can be used for in vitro and in vivo diagnosis of fish-induced food allergy. Our finding that the ape-form of parvalbumin had a greatly reduced IgE binding capacity indicates that this form may be a candidate for safe immunotherapy of fish-related food allergy.	52	90	2000	9	10.1136/gut.46.5.661	Gastroenterology & Hepatology
House-dust-mite sublingual-swallow immunotherapy (SLIT) in perennial rhinitis: a double-blind, placebo-controlled study. Background: The safety and efficacy of sublingual-swallow immunotherapy (SLIT) in rhinitis caused by house-dust mite were evaluated in a double-blind, placebo-controlled study including 75 patients for 24 months. Methods: Patients received either placebo or SLIT with a standardized Dermatophagoides pteronyssinus (D.pt.) - D. farinae (D.f.) 50/50 extract. The mean cumulative dose was 90 000 IR, equivalent to 2.2 mg of Der p 1 and 1.7 mg of Der f I. Symptom and medication scores were assessed throughout the study. Exposure to house-dust mite, skin sensitivity, and serum specific IgE and IgG4 were assessed before starting treatment and after 12 and 24 months. Results: Seventy-two patients (36 active-36 placebo) were eligible for intent-to-treat analysis. Thirty-six patients dropped out of the study. The number of patients who dropped out due to lack of efficacy was eight out of 37 (21.6%) in the active treatment group compared to 15 out of 38 (39.5%) in the placebo group (chi-square = 2.81, P = 0.09). Total symptom and medication scores decreased significantly after 12 and 24 months (P < 0.05) of treatment in both groups, but no significant difference was observed between the active and placebo groups. After 24 months, the number of patients with high levels of indoor allergenic load decreased significantly in both groups compared to baseline data (P = 0.01). Specific IgE (D.pt. and D.f.) increased significantly in the active treatment group after 12 and 24 months, while no change was observed in the placebo group. Specific IgG4 levels were not significantly modified in either group. Two patients in each group reported mild adverse effects. No severe adverse effects were reported. Conclusions: We conclude that SLIT in rhinitis caused by house-dust mite was safe, but there was a lack of consistent clinical benefit compared to placebo, probably due to the impact of the allergen avoidance measures that lowered the allergen burden.. house-dust mite| perennial rhinitis| sublingual immunotherapy|controlled trial| allergic rhinitis| pollen extract| asthma| rhinoconjunctivitis| efficacy| children| exposure| ige.	APR-2000	house-dust mite| perennial rhinitis| sublingual immunotherapy|controlled trial| allergic rhinitis| pollen extract| asthma| rhinoconjunctivitis| efficacy| children| exposure| ige	Guez, S; Vatrinet, C; Fadel, R; Andre, C	House-dust-mite sublingual-swallow immunotherapy (SLIT) in perennial rhinitis: a double-blind, placebo-controlled study		ALLERGY	house-dust mite; perennial rhinitis; sublingual immunotherapy	CONTROLLED TRIAL; ALLERGIC RHINITIS; POLLEN EXTRACT; ASTHMA; RHINOCONJUNCTIVITIS; EFFICACY; CHILDREN; EXPOSURE; IGE	Background: The safety and efficacy of sublingual-swallow immunotherapy (SLIT) in rhinitis caused by house-dust mite were evaluated in a double-blind, placebo-controlled study including 75 patients for 24 months. Methods: Patients received either placebo or SLIT with a standardized Dermatophagoides pteronyssinus (D.pt.) - D. farinae (D.f.) 50/50 extract. The mean cumulative dose was 90 000 IR, equivalent to 2.2 mg of Der p 1 and 1.7 mg of Der f I. Symptom and medication scores were assessed throughout the study. Exposure to house-dust mite, skin sensitivity, and serum specific IgE and IgG4 were assessed before starting treatment and after 12 and 24 months. Results: Seventy-two patients (36 active-36 placebo) were eligible for intent-to-treat analysis. Thirty-six patients dropped out of the study. The number of patients who dropped out due to lack of efficacy was eight out of 37 (21.6%) in the active treatment group compared to 15 out of 38 (39.5%) in the placebo group (chi-square = 2.81, P = 0.09). Total symptom and medication scores decreased significantly after 12 and 24 months (P < 0.05) of treatment in both groups, but no significant difference was observed between the active and placebo groups. After 24 months, the number of patients with high levels of indoor allergenic load decreased significantly in both groups compared to baseline data (P = 0.01). Specific IgE (D.pt. and D.f.) increased significantly in the active treatment group after 12 and 24 months, while no change was observed in the placebo group. Specific IgG4 levels were not significantly modified in either group. Two patients in each group reported mild adverse effects. No severe adverse effects were reported. Conclusions: We conclude that SLIT in rhinitis caused by house-dust mite was safe, but there was a lack of consistent clinical benefit compared to placebo, probably due to the impact of the allergen avoidance measures that lowered the allergen burden.	25	90	2000	7	10.1034/j.1398-9995.2000.00413.x	Allergy; Immunology
"Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. Objective To describe the potential benefits and harms of oseltamivir by reviewing all clinical study reports (or similar document when no clinical study report exists) of randomised placebo controlled trials and regulatory comments (""regulatory information""). Design Systematic review of regulatory information. Data sources Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers. Eligibility criteria for selecting studies Randomised placebo controlled trials on adults and children who had confirmed or suspected exposure to natural influenza. Main outcome measures Time to first alleviation of symptoms, influenza outcomes, complications, admissions to hospital, and adverse events in the intention to treat population. Results From the European Medicines Agency and Roche, we obtained clinical study reports for 83 trials. We included 23 trials in stage 1 (reliability and completeness screen) and 20 in stage 2 (formal analysis). In treatment trials on adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval 8.4 to 25.1 hours, P<0.001). There was no effect in children with asthma, but there was an effect in otherwise healthy children (mean difference 29 hours, 95% confidence interval 12 to 47 hours, P=0.001). In treatment trials there was no difference in admissions to hospital in adults (risk difference 0.15%, 95% confidence interval -0.91% to 0.78%, P=0.84) and sparse data in children and for prophylaxis. In adult treatment trials, oseltamivir reduced investigator mediated unverified pneumonia (risk difference 1.00%, 0.22% to 1.49%; number needed to treat to benefit (NNTB) 100, 95% confidence interval 67 to 451). The effect was not statistically significant in the five trials that used a more detailed diagnostic form for ""pneumonia,"" and no clinical study reports reported laboratory or diagnostic confirmation of ""pneumonia."" The effect on unverified pneumonia in children and for prophylaxis was not significant. There was no significant reduction in risk of unverified bronchitis, otitis media, sinusitis, or any complication classified as serious or that led to study withdrawal. 14 of 20 trials prompted participants to self report all secondary illnesses to an investigator. Oseltamivir in the treatment of adults increased the risk of nausea (risk difference 3.66%, 0.90% to 7.39%; number needed to treat to harm (NNTH) 28, 95% confidence interval 14 to 112) and vomiting (4.56%, 2.39% to 7.58%; 22, 14 to 42). In treatment of children, oseltamivir induced vomiting (5.34%, 1.75% to 10.29%; 19, 10 to 57). In prophylaxis trials, oseltamivir reduced symptomatic influenza in participants by 55% (3.05%, 1.83% to 3.88%; NNTB 33, 26 to 55) and households (13.6%, 9.52% to 15.47%; NNTB 7, 6 to 11) based on one study, but there was no significant effect on asymptomatic influenza and no evidence of a reduction in transmission. In prophylaxis studies, oseltamivir increased the risk of psychiatric adverse events during the combined ""on-treatment"" and ""off-treatment"" periods (risk difference 1.06%, 0.07% to 2.76%; NNTH 94, 36 to 1538) and there was a dose-response effect on psychiatric events in two ""pivotal"" treatment trials of oseltamivir, at 75 mg (standard dose) and 150 mg (high dose) twice daily (P=0.038). In prophylaxis studies, oseltamivir increased the risk of headaches on-treatment (risk difference 3.15%, 0.88% to 5.78%; NNTH 32, 18 to 115), renal events with treatment (0.67%, -0.01% to 2.93%), and nausea while receiving treatment (4.15%, 0.86% to 9.51%; NNTH 25, 11 to 116). Conclusions In prophylactic studies oseltamivir reduces the proportion of symptomatic influenza. In treatment studies it also modestly reduces the time to first alleviation of symptoms, but it causes nausea and vomiting and increases the risk of headaches and renal and psychiatric syndromes. The evidence of clinically significant effects on complications and viral transmission is limited because of rarity of such events and problems with study design. The trade-off between benefits and harms should be borne in mind when making decisions to use oseltamivir for treatment, prophylaxis, or stockpiling.. neuropsychiatric adverse events| prophylaxis."	APR 9-2014	neuropsychiatric adverse events| prophylaxis	Jefferson, T; Jones, M; Doshi, P; Spencer, EA; Onakpoya, I; Heneghan, CJ	Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments		BMJ-BRITISH MEDICAL JOURNAL		NEUROPSYCHIATRIC ADVERSE EVENTS; PROPHYLAXIS	"Objective To describe the potential benefits and harms of oseltamivir by reviewing all clinical study reports (or similar document when no clinical study report exists) of randomised placebo controlled trials and regulatory comments (""regulatory information""). Design Systematic review of regulatory information. Data sources Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers. Eligibility criteria for selecting studies Randomised placebo controlled trials on adults and children who had confirmed or suspected exposure to natural influenza. Main outcome measures Time to first alleviation of symptoms, influenza outcomes, complications, admissions to hospital, and adverse events in the intention to treat population. Results From the European Medicines Agency and Roche, we obtained clinical study reports for 83 trials. We included 23 trials in stage 1 (reliability and completeness screen) and 20 in stage 2 (formal analysis). In treatment trials on adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval 8.4 to 25.1 hours, P<0.001). There was no effect in children with asthma, but there was an effect in otherwise healthy children (mean difference 29 hours, 95% confidence interval 12 to 47 hours, P=0.001). In treatment trials there was no difference in admissions to hospital in adults (risk difference 0.15%, 95% confidence interval -0.91% to 0.78%, P=0.84) and sparse data in children and for prophylaxis. In adult treatment trials, oseltamivir reduced investigator mediated unverified pneumonia (risk difference 1.00%, 0.22% to 1.49%; number needed to treat to benefit (NNTB) 100, 95% confidence interval 67 to 451). The effect was not statistically significant in the five trials that used a more detailed diagnostic form for ""pneumonia,"" and no clinical study reports reported laboratory or diagnostic confirmation of ""pneumonia."" The effect on unverified pneumonia in children and for prophylaxis was not significant. There was no significant reduction in risk of unverified bronchitis, otitis media, sinusitis, or any complication classified as serious or that led to study withdrawal. 14 of 20 trials prompted participants to self report all secondary illnesses to an investigator. Oseltamivir in the treatment of adults increased the risk of nausea (risk difference 3.66%, 0.90% to 7.39%; number needed to treat to harm (NNTH) 28, 95% confidence interval 14 to 112) and vomiting (4.56%, 2.39% to 7.58%; 22, 14 to 42). In treatment of children, oseltamivir induced vomiting (5.34%, 1.75% to 10.29%; 19, 10 to 57). In prophylaxis trials, oseltamivir reduced symptomatic influenza in participants by 55% (3.05%, 1.83% to 3.88%; NNTB 33, 26 to 55) and households (13.6%, 9.52% to 15.47%; NNTB 7, 6 to 11) based on one study, but there was no significant effect on asymptomatic influenza and no evidence of a reduction in transmission. In prophylaxis studies, oseltamivir increased the risk of psychiatric adverse events during the combined ""on-treatment"" and ""off-treatment"" periods (risk difference 1.06%, 0.07% to 2.76%; NNTH 94, 36 to 1538) and there was a dose-response effect on psychiatric events in two ""pivotal"" treatment trials of oseltamivir, at 75 mg (standard dose) and 150 mg (high dose) twice daily (P=0.038). In prophylaxis studies, oseltamivir increased the risk of headaches on-treatment (risk difference 3.15%, 0.88% to 5.78%; NNTH 32, 18 to 115), renal events with treatment (0.67%, -0.01% to 2.93%), and nausea while receiving treatment (4.15%, 0.86% to 9.51%; NNTH 25, 11 to 116). Conclusions In prophylactic studies oseltamivir reduces the proportion of symptomatic influenza. In treatment studies it also modestly reduces the time to first alleviation of symptoms, but it causes nausea and vomiting and increases the risk of headaches and renal and psychiatric syndromes. The evidence of clinically significant effects on complications and viral transmission is limited because of rarity of such events and problems with study design. The trade-off between benefits and harms should be borne in mind when making decisions to use oseltamivir for treatment, prophylaxis, or stockpiling."	20	89	2014	18	10.1136/bmj.g2545	General & Internal Medicine
Gut microbiota, probiotics, and vitamin D: Interrelated exposures influencing allergy, asthma, and obesity?. Current evidence supports a role for gut colonization in promoting and maintaining a balanced immune response in early life. An altered or less diverse gut microbiota composition has been associated with atopic diseases, obesity, or both. Moreover, certain gut microbial strains have been shown to inhibit or attenuate immune responses associated with chronic inflammation in experimental models. However, there has been no fully adequate longitudinal study of the relation between the neonatal gut microbiota and the development of allergic diseases (eg, atopic asthma) and obesity. The emergence of promising experimental studies has led to several clinical trials of probiotics (live bacteria given orally that allow for intestinal colonization) in human subjects. Probiotic trials thus far have failed to show a consistent preventive or therapeutic effect on asthma or obesity. Previous trials of probiotics have been limited by small sample size, short duration of follow-up, or lack of state-of-the art analyses of the gut microbiota. Finally, there is emerging evidence that the vitamin D pathway might be important in gut homeostasis and in signaling between the microbiota and the host. Given the complexity of the gut micriobiota, additional research is needed before we can confidently establish whether its manipulation in early life can prevent or treat asthma, obesity, or both. (J Allergy Clin Immunol 2011;127:1087-94.). microbiota| asthma| obesity| allergic| eczema| vitamin d| probiotics| cytokines|placebo-controlled trial| diet-induced obesity| randomized controlled-trial| body-mass index| age 5 years| antibiotic use| intestinal microflora| early-life| 1st year| airway inflammation.	MAY-2011	microbiota| asthma| obesity| allergic| eczema| vitamin d| probiotics| cytokines|placebo-controlled trial| diet-induced obesity| randomized controlled-trial| body-mass index| age 5 years| antibiotic use| intestinal microflora| early-life| 1st year| airway inflammation	Ly, NP; Litonjua, A; Gold, DR; Celedon, JC	Gut microbiota, probiotics, and vitamin D: Interrelated exposures influencing allergy, asthma, and obesity?		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Microbiota; asthma; obesity; allergic; eczema; vitamin D; probiotics; cytokines	PLACEBO-CONTROLLED TRIAL; DIET-INDUCED OBESITY; RANDOMIZED CONTROLLED-TRIAL; BODY-MASS INDEX; AGE 5 YEARS; ANTIBIOTIC USE; INTESTINAL MICROFLORA; EARLY-LIFE; 1ST YEAR; AIRWAY INFLAMMATION	Current evidence supports a role for gut colonization in promoting and maintaining a balanced immune response in early life. An altered or less diverse gut microbiota composition has been associated with atopic diseases, obesity, or both. Moreover, certain gut microbial strains have been shown to inhibit or attenuate immune responses associated with chronic inflammation in experimental models. However, there has been no fully adequate longitudinal study of the relation between the neonatal gut microbiota and the development of allergic diseases (eg, atopic asthma) and obesity. The emergence of promising experimental studies has led to several clinical trials of probiotics (live bacteria given orally that allow for intestinal colonization) in human subjects. Probiotic trials thus far have failed to show a consistent preventive or therapeutic effect on asthma or obesity. Previous trials of probiotics have been limited by small sample size, short duration of follow-up, or lack of state-of-the art analyses of the gut microbiota. Finally, there is emerging evidence that the vitamin D pathway might be important in gut homeostasis and in signaling between the microbiota and the host. Given the complexity of the gut micriobiota, additional research is needed before we can confidently establish whether its manipulation in early life can prevent or treat asthma, obesity, or both. (J Allergy Clin Immunol 2011;127:1087-94.)	130	89	2011	8	10.1016/j.jaci.2011.02.015	Allergy; Immunology
99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian medicine and the 'hygiene' or 'old friends' hypothesis. P>The current synthesis of the 'hygiene hypothesis' suggests that the recent increase in chronic inflammatory disorders is at least partly attributable to immunodysregulation resulting from lack of exposure to microorganisms that have evolved an essential role in the establishment of the immune system. This document provides a background for discussion of the following propositions. The essential role of these organisms is an example of 'evolved dependence'. The most relevant organisms are those that co-evolved with mammals, and already accompanied early hominids in the Paleolithic. More recently evolved 'childhood infections' are not likely to have evolved this role, and recent epidemiology supports this contention. This mechanism is interacting with other modern environmental changes that also lead to enhanced inflammatory responses [inappropriate diet, obesity, psychological stress, vitamin D deficiency, pollution (dioxins), etc.]. The range of chronic inflammatory disorders that is affected is potentially larger than usually assumed [allergies, autoimmunity, inflammatory bowel disease, but also vascular disease, some cancers, depression/anxiety (when accompanied by raised inflammatory cytokines), and perhaps neurodegenerative disorders and type 2 diabetes].. darwinian medicine| dendritic cells| 'hygiene hypothesis'| 'old friends' hypothesis| t(reg)|innate immunity| hay-fever| disease| asthma| viruses| pathogenesis| association| evolution| parasites| lessons.	APR-2010	darwinian medicine| dendritic cells| 'hygiene hypothesis'| 'old friends' hypothesis| t(reg)|innate immunity| hay-fever| disease| asthma| viruses| pathogenesis| association| evolution| parasites| lessons	Rook, GAW	99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Darwinian medicine and the 'hygiene' or 'old friends' hypothesis		CLINICAL AND EXPERIMENTAL IMMUNOLOGY	Darwinian medicine; dendritic cells; 'hygiene hypothesis'; 'old friends' hypothesis; T(reg)	INNATE IMMUNITY; HAY-FEVER; DISEASE; ASTHMA; VIRUSES; PATHOGENESIS; ASSOCIATION; EVOLUTION; PARASITES; LESSONS	P>The current synthesis of the 'hygiene hypothesis' suggests that the recent increase in chronic inflammatory disorders is at least partly attributable to immunodysregulation resulting from lack of exposure to microorganisms that have evolved an essential role in the establishment of the immune system. This document provides a background for discussion of the following propositions. The essential role of these organisms is an example of 'evolved dependence'. The most relevant organisms are those that co-evolved with mammals, and already accompanied early hominids in the Paleolithic. More recently evolved 'childhood infections' are not likely to have evolved this role, and recent epidemiology supports this contention. This mechanism is interacting with other modern environmental changes that also lead to enhanced inflammatory responses [inappropriate diet, obesity, psychological stress, vitamin D deficiency, pollution (dioxins), etc.]. The range of chronic inflammatory disorders that is affected is potentially larger than usually assumed [allergies, autoimmunity, inflammatory bowel disease, but also vascular disease, some cancers, depression/anxiety (when accompanied by raised inflammatory cytokines), and perhaps neurodegenerative disorders and type 2 diabetes].	56	89	2010	10	10.1111/j.1365-2249.2010.04133.x	Immunology
High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: A randomized, placebo-controlled, crossover study. Background: Increased dosing of nonsedating antihistamines is recommended by the current European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum guidelines on patients with acquired cold urticaria (ACU) who do not respond satisfactorily to the standard dose. Prospective data supporting this recommendation are scant. Objective: We sought to assess the effects of 5 and 20 mg of desloratadine and placebo on cold-induced urticarial reactions in patients with ACU. Methods: In this prospective, randomized, double-blind, 3-way crossover trial, patients with ACU (n = 30) received placebo, 5 mg of desloratadine, and 20 mg of desloratadine every day each for 7 days separated by 14-day washout periods. At the end of each treatment, patients underwent cold provocation with the TempTest 2.0/2.1 system, and urticarial reactions were assessed by using digital 3-dimensional time-lapse photography and thermography; the critical temperature threshold (CTT) and critical stimulation time threshold (CSTT) were measured. Adverse events (AEs) reported during the study were assessed. Results: Compared with placebo, 7 days of desloratadine at 5 and 20 mg/d significantly reduced the volume of cold-induced wheals and areas of hyperthermic skin and improved CTT and CSTT results. Desloratadine at 20 mg/d significantly reduced cold-induced wheal volume and CTT and CSTT values versus desloratadine at 5 mg/d. Desloratadine was well tolerated, with no increased rate of somnolence or other AEs with 20 mg of desloratadine. Conclusions: Desloratadine at standard and high doses significantly improved objective signs of ACU provoked by cold exposure. Desloratadine at 4 times the standard dose significantly reduced ACU lesion severity versus 5 mg of desloratadine without an increase in AEs. This study supports current guidelines that increased desloratadine dosing might benefit patients with urticaria who do not respond to standard doses. (J Allergy Clin Immunol 2009;123:672-9.). urticaria| cold| chronic| objective| antihistamine| desloratadine|chronic idiopathic urticaria| double-blind| eaaci/ga(2)len/edf guideline| multicenter| diagnosis| efficacy| safety| adults| trial.	MAR-2009	urticaria| cold| chronic| objective| antihistamine| desloratadine|chronic idiopathic urticaria| double-blind| eaaci/ga(2)len/edf guideline| multicenter| diagnosis| efficacy| safety| adults| trial	Siebenhaar, F; Degener, F; Zuberbier, T; Martus, P; Maurer, M	High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: A randomized, placebo-controlled, crossover study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Urticaria; cold; chronic; objective; antihistamine; desloratadine	CHRONIC IDIOPATHIC URTICARIA; DOUBLE-BLIND; EAACI/GA(2)LEN/EDF GUIDELINE; MULTICENTER; DIAGNOSIS; EFFICACY; SAFETY; ADULTS; TRIAL	Background: Increased dosing of nonsedating antihistamines is recommended by the current European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum guidelines on patients with acquired cold urticaria (ACU) who do not respond satisfactorily to the standard dose. Prospective data supporting this recommendation are scant. Objective: We sought to assess the effects of 5 and 20 mg of desloratadine and placebo on cold-induced urticarial reactions in patients with ACU. Methods: In this prospective, randomized, double-blind, 3-way crossover trial, patients with ACU (n = 30) received placebo, 5 mg of desloratadine, and 20 mg of desloratadine every day each for 7 days separated by 14-day washout periods. At the end of each treatment, patients underwent cold provocation with the TempTest 2.0/2.1 system, and urticarial reactions were assessed by using digital 3-dimensional time-lapse photography and thermography; the critical temperature threshold (CTT) and critical stimulation time threshold (CSTT) were measured. Adverse events (AEs) reported during the study were assessed. Results: Compared with placebo, 7 days of desloratadine at 5 and 20 mg/d significantly reduced the volume of cold-induced wheals and areas of hyperthermic skin and improved CTT and CSTT results. Desloratadine at 20 mg/d significantly reduced cold-induced wheal volume and CTT and CSTT values versus desloratadine at 5 mg/d. Desloratadine was well tolerated, with no increased rate of somnolence or other AEs with 20 mg of desloratadine. Conclusions: Desloratadine at standard and high doses significantly improved objective signs of ACU provoked by cold exposure. Desloratadine at 4 times the standard dose significantly reduced ACU lesion severity versus 5 mg of desloratadine without an increase in AEs. This study supports current guidelines that increased desloratadine dosing might benefit patients with urticaria who do not respond to standard doses. (J Allergy Clin Immunol 2009;123:672-9.)	16	89	2009	8	10.1016/j.jaci.2008.12.008	Allergy; Immunology
Novel long-acting bronchodilators for COPD and asthma. An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once-daily beta(2)-agonists or ultra long-acting beta(2)-agonists (LABAs) such as carmoterol, indacaterol, GSK-159797, GSK-597901, GSK-159802, GSK-642444 and GSK-678007 are under development for the treatment of asthma and COPD. Also some new long-acting antimuscarinic agents (LAMAs) such as aclidinium, LAS-35201, GSK656398, GSK233705, NVA-237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long-acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once-daily dual-action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M(3) antagonist-beta(2) agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products.. aclidinium| asthma| bronchodilators| carmoterol| chronic obstructive pulmonary disease| combination therapy| indacaterol| long-acting antimuscarinic agents| nva237| ultra-long-acting beta-agonists|obstructive pulmonary-disease| air-flow obstruction| beta(2)-adrenoceptor agonist| guinea-pigs| pharmacological characterization| adrenoceptor agonist| positive interaction| global strategy| stable copd| tiotropium.	OCT-2008	aclidinium| asthma| bronchodilators| carmoterol| chronic obstructive pulmonary disease| combination therapy| indacaterol| long-acting antimuscarinic agents| nva237| ultra-long-acting beta-agonists|obstructive pulmonary-disease| air-flow obstruction| beta(2)-adrenoceptor agonist| guinea-pigs| pharmacological characterization| adrenoceptor agonist| positive interaction| global strategy| stable copd| tiotropium	Cazzola, M; Matera, MG	Novel long-acting bronchodilators for COPD and asthma		BRITISH JOURNAL OF PHARMACOLOGY	aclidinium; asthma; bronchodilators; carmoterol; chronic obstructive pulmonary disease; combination therapy; indacaterol; long-acting antimuscarinic agents; NVA237; ultra-long-acting beta-agonists	OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW OBSTRUCTION; BETA(2)-ADRENOCEPTOR AGONIST; GUINEA-PIGS; PHARMACOLOGICAL CHARACTERIZATION; ADRENOCEPTOR AGONIST; POSITIVE INTERACTION; GLOBAL STRATEGY; STABLE COPD; TIOTROPIUM	An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once-daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once-daily beta(2)-agonists or ultra long-acting beta(2)-agonists (LABAs) such as carmoterol, indacaterol, GSK-159797, GSK-597901, GSK-159802, GSK-642444 and GSK-678007 are under development for the treatment of asthma and COPD. Also some new long-acting antimuscarinic agents (LAMAs) such as aclidinium, LAS-35201, GSK656398, GSK233705, NVA-237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long-acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once-daily dual-action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M(3) antagonist-beta(2) agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products.	68	89	2008	9	10.1038/bjp.2008.284	Pharmacology & Pharmacy
Age at first introduction of cow milk products and other food products in relation to infant atopic manifestations in the first 2 years of life: The KOALA birth cohort study. OBJECTIVES. Scientific evidence is scarce about timing of solid-food introduction and its association with the development of atopy. We aimed to evaluate any associations between the introduction of cow milk products/other solid food products and infant atopic manifestations in the second year of life, taking into account reverse causation. METHODS. Data from 2558 infants in an ongoing prospective birth cohort study in the Netherlands were analyzed. Data on the main determinants (introduction of cow milk products and other food products), outcomes (eczema; atopic dermatitis [United Kingdom Working Party criteria]; recurrent wheeze; any sensitization; sensitization against cow milk, hen egg, peanut, and at least 1 inhalant allergen), and confounders were collected by repeated questionnaires at 34 weeks of gestation and 3, 7, 12, and 24 months postpartum. Information on sensitization was gathered by venous blood collections performed during home visits at age 2. Analyses were performed by multiple logistic regression analyses. RESULTS. More delay in introduction of cow milk products was associated with a higher risk for eczema. In addition, a delayed introduction of other food products was associated with an increased risk for atopy development at the age of 2 years. Exclusion of infants with early symptoms of eczema and recurrent wheeze (to avoid reverse causation) did not essentially change our results. DISCUSSION. Delaying the introduction of cow milk or other food products may not be favorable in preventing the development of atopy.. cow milk| solids| atopy| reverse causation| oral tolerance| infant|brief neonatal exposure| asthma| allergy| children| sensitization| prevention| eczema| risk| association| dermatitis.	JUL-2008	cow milk| solids| atopy| reverse causation| oral tolerance| infant|brief neonatal exposure| asthma| allergy| children| sensitization| prevention| eczema| risk| association| dermatitis	Snijders, BEP; Thijs, C; van Ree, R; van den Brandt, PA	Age at first introduction of cow milk products and other food products in relation to infant atopic manifestations in the first 2 years of life: The KOALA birth cohort study		PEDIATRICS	cow milk; solids; atopy; reverse causation; oral tolerance; infant	BRIEF NEONATAL EXPOSURE; ASTHMA; ALLERGY; CHILDREN; SENSITIZATION; PREVENTION; ECZEMA; RISK; ASSOCIATION; DERMATITIS	OBJECTIVES. Scientific evidence is scarce about timing of solid-food introduction and its association with the development of atopy. We aimed to evaluate any associations between the introduction of cow milk products/other solid food products and infant atopic manifestations in the second year of life, taking into account reverse causation. METHODS. Data from 2558 infants in an ongoing prospective birth cohort study in the Netherlands were analyzed. Data on the main determinants (introduction of cow milk products and other food products), outcomes (eczema; atopic dermatitis [United Kingdom Working Party criteria]; recurrent wheeze; any sensitization; sensitization against cow milk, hen egg, peanut, and at least 1 inhalant allergen), and confounders were collected by repeated questionnaires at 34 weeks of gestation and 3, 7, 12, and 24 months postpartum. Information on sensitization was gathered by venous blood collections performed during home visits at age 2. Analyses were performed by multiple logistic regression analyses. RESULTS. More delay in introduction of cow milk products was associated with a higher risk for eczema. In addition, a delayed introduction of other food products was associated with an increased risk for atopy development at the age of 2 years. Exclusion of infants with early symptoms of eczema and recurrent wheeze (to avoid reverse causation) did not essentially change our results. DISCUSSION. Delaying the introduction of cow milk or other food products may not be favorable in preventing the development of atopy.	26	89	2008	8	10.1542/peds.2007-1651	Pediatrics
Recent evidence for adverse effects of residential proximity to traffic sources on asthma. There is consistent evidence that living near traffic sources is associated with asthma occurrence and exacerbations. Future studies have the opportunity to improve exposure estimates by measuring traffic-related pollutants near homes and schools and including time/activity patterns in prediction models. Further research is also warranted to investigate the differential impact of traffic by genetic and other susceptibility factors and to identify specific pollutants that underlie the adverse effect of traffic on asthma.. air pollution| asthma| freeway| traffic| wheeze|volatile organic-compounds| 3 european areas| air-pollution| respiratory symptoms| nitrogen-dioxide| adult asthma| exposure| children| association| cohort.	JAN-2008	air pollution| asthma| freeway| traffic| wheeze|volatile organic-compounds| 3 european areas| air-pollution| respiratory symptoms| nitrogen-dioxide| adult asthma| exposure| children| association| cohort	Salam, MT; Islam, T; Gilliland, FD	Recent evidence for adverse effects of residential proximity to traffic sources on asthma		CURRENT OPINION IN PULMONARY MEDICINE	air pollution; asthma; freeway; traffic; wheeze	VOLATILE ORGANIC-COMPOUNDS; 3 EUROPEAN AREAS; AIR-POLLUTION; RESPIRATORY SYMPTOMS; NITROGEN-DIOXIDE; ADULT ASTHMA; EXPOSURE; CHILDREN; ASSOCIATION; COHORT	There is consistent evidence that living near traffic sources is associated with asthma occurrence and exacerbations. Future studies have the opportunity to improve exposure estimates by measuring traffic-related pollutants near homes and schools and including time/activity patterns in prediction models. Further research is also warranted to investigate the differential impact of traffic by genetic and other susceptibility factors and to identify specific pollutants that underlie the adverse effect of traffic on asthma.	39	89	2008	6	10.1097/MCP.0b013e3282f1987a	Respiratory System
"Airway eosinophils: Allergic inflammation recruited professional antigen-presenting cells. The capacity of airway eosinophils, potentially pertinent to allergic diseases of the upper and lower airways, to function as professional APCs, those specifically able to elicit responses from unprimed, Ag-naive CD4(+) T cells has been uncertain. We investigated whether airway eosinophils are capable of initiating naive T cell responses in vivo. Eosinophils, isolated free of other APCs from the spleens of IL-5 transgenic mice, following culture with GM-CSF expressed MHC class 11 and the costimulatory proteins, CD40, CD80, and CD86. Eosinophils, incubated with OVA Ag in vitro, were instilled intratracheally into wild-type recipient mice that adoptively received i.v. infusions of OVA Ag-specific CD4(+) T cells from OVA TCR transgenic mice. OVA-exposed eosinophils elicited activation (CD69 expression), proliferation (BrdU incorporation), and IL-4, but not IFN-gamma, cytokine production by OVA-specific CD4(+) T cells in paratracheal lymph nodes (LN). Exposure of eosinophils to lysosomotropic NH4Cl which inhibits Ag processing, blocked each of these eosinophil-mediated activation responses of CD4(+) T cells. By three-color fluorescence microscopy, OVA Ag-loaded eosinophil APCs were physically interacting with naive OVA-specific CD4(+) T cells in paratracheal LN after eosinophil airway instillation. Thus, recruited luminal airway eosinophils are distinct allergic ""inflammatory"" professional APCs able to activate primary CD4(+) T cell responses in regional LNs.. cd4 t-cells| dendritic cells| in-vivo| hla-dr| respiratory-tract| lymph-nodes| human lung| asthma| expression| challenge."	DEC 1-2007	cd4 t-cells| dendritic cells| in-vivo| hla-dr| respiratory-tract| lymph-nodes| human lung| asthma| expression| challenge	Wang, HB; Ghiran, I; Matthaei, K; Weller, PF	Airway eosinophils: Allergic inflammation recruited professional antigen-presenting cells		JOURNAL OF IMMUNOLOGY		CD4 T-CELLS; DENDRITIC CELLS; IN-VIVO; HLA-DR; RESPIRATORY-TRACT; LYMPH-NODES; HUMAN LUNG; ASTHMA; EXPRESSION; CHALLENGE	"The capacity of airway eosinophils, potentially pertinent to allergic diseases of the upper and lower airways, to function as professional APCs, those specifically able to elicit responses from unprimed, Ag-naive CD4(+) T cells has been uncertain. We investigated whether airway eosinophils are capable of initiating naive T cell responses in vivo. Eosinophils, isolated free of other APCs from the spleens of IL-5 transgenic mice, following culture with GM-CSF expressed MHC class 11 and the costimulatory proteins, CD40, CD80, and CD86. Eosinophils, incubated with OVA Ag in vitro, were instilled intratracheally into wild-type recipient mice that adoptively received i.v. infusions of OVA Ag-specific CD4(+) T cells from OVA TCR transgenic mice. OVA-exposed eosinophils elicited activation (CD69 expression), proliferation (BrdU incorporation), and IL-4, but not IFN-gamma, cytokine production by OVA-specific CD4(+) T cells in paratracheal lymph nodes (LN). Exposure of eosinophils to lysosomotropic NH4Cl which inhibits Ag processing, blocked each of these eosinophil-mediated activation responses of CD4(+) T cells. By three-color fluorescence microscopy, OVA Ag-loaded eosinophil APCs were physically interacting with naive OVA-specific CD4(+) T cells in paratracheal LN after eosinophil airway instillation. Thus, recruited luminal airway eosinophils are distinct allergic ""inflammatory"" professional APCs able to activate primary CD4(+) T cell responses in regional LNs."	48	89	2007	8		Immunology
Measuring air quality to protect children from secondhand smoke in cars. Background: Secondhand tobacco smoke (SHS) is a major, preventable contributor to acute and chronic adverse health outcomes that affect children disproportionately. The predominant source of SHS among children is domestic exposure, and while up to two thirds of U.S. households have car smoking bans, an unacceptable number of children remain vulnerable. To help promote more effective protection through legislation, health communication strategies, or behavioral interventions, data demonstrating the adverse effect of SHS on air quality in cars are needed. Methods: Secondhand tobacco smoke in a motor vehicle under actual driving conditions was monitored by measuring respirable suspended particles (RSPs) of less than 2.5 microns in diameter, and carbon monoxide. Forty-five driving trials were conducted, using teams of volunteer drivers and smokers recruited from the general community. Three smoking conditions (nonsmoking baseline, active smoking, and immediate post-smoking period, each 5 minutes) were crossed with two ventilation conditions (windows open, closed) in a 3 x 2 within-sessions factorial design. Results: The highest mean observed RSP level was 271 mu g/m(3), which is unsafe, particularly for children. Peak RSP levels were considerably higher. RSPs and carbon monoxide increased significantly from baseline after smoking, and these increases were greatest during the closed ventilation condition, compared with open ventilation. Conclusions: Private passenger cars are a domestic environment with the potential to yield unsafe levels of SHS contaminants. These data may assist policymakers and health advocates to promote protective strategies to ensure smoke-free domestic environments for children.. environmental tobacco-smoke| nutrition examination survey| infant-death-syndrome| 3rd national-health| passive smoking| exposure| asthma| home| households| childhood.	NOV-2006	environmental tobacco-smoke| nutrition examination survey| infant-death-syndrome| 3rd national-health| passive smoking| exposure| asthma| home| households| childhood	Rees, VW; Connolly, GN	Measuring air quality to protect children from secondhand smoke in cars		AMERICAN JOURNAL OF PREVENTIVE MEDICINE		ENVIRONMENTAL TOBACCO-SMOKE; NUTRITION EXAMINATION SURVEY; INFANT-DEATH-SYNDROME; 3RD NATIONAL-HEALTH; PASSIVE SMOKING; EXPOSURE; ASTHMA; HOME; HOUSEHOLDS; CHILDHOOD	Background: Secondhand tobacco smoke (SHS) is a major, preventable contributor to acute and chronic adverse health outcomes that affect children disproportionately. The predominant source of SHS among children is domestic exposure, and while up to two thirds of U.S. households have car smoking bans, an unacceptable number of children remain vulnerable. To help promote more effective protection through legislation, health communication strategies, or behavioral interventions, data demonstrating the adverse effect of SHS on air quality in cars are needed. Methods: Secondhand tobacco smoke in a motor vehicle under actual driving conditions was monitored by measuring respirable suspended particles (RSPs) of less than 2.5 microns in diameter, and carbon monoxide. Forty-five driving trials were conducted, using teams of volunteer drivers and smokers recruited from the general community. Three smoking conditions (nonsmoking baseline, active smoking, and immediate post-smoking period, each 5 minutes) were crossed with two ventilation conditions (windows open, closed) in a 3 x 2 within-sessions factorial design. Results: The highest mean observed RSP level was 271 mu g/m(3), which is unsafe, particularly for children. Peak RSP levels were considerably higher. RSPs and carbon monoxide increased significantly from baseline after smoking, and these increases were greatest during the closed ventilation condition, compared with open ventilation. Conclusions: Private passenger cars are a domestic environment with the potential to yield unsafe levels of SHS contaminants. These data may assist policymakers and health advocates to promote protective strategies to ensure smoke-free domestic environments for children.	41	89	2006	6	10.1016/j.ampere.2006.07.021	Public, Environmental & Occupational Health; General & Internal Medicine
Child health and the environment: The INMA spanish study. The INMA (INfancia y Medio Ambiente [Environment and Childhood]) is a population-based cohort study in different Spanish cities, that focuses on prenatal environmental exposures and growth, development and health from early fetal life until childhood. The study focuses on five primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) asthma and allergies; (4) sexual and reproductive development; and (5) environmental exposure pathways. The general aims of the project are: (1) to describe the degree of individual prenatal exposure to environmental pollutants, and the internal dose of chemicals during pregnancy, at birth and during childhood in Spain; (2) to evaluate the impact of the exposure to different contaminants on fetal and infant growth, health and development; (3) to evaluate the role of diet on fetal and infant growth, health and development; and (4) to evaluate the interaction between persistent pollutants, nutrients and genetic determinants on fetal and infant growth, health and development. Extensive assessments will be carried out on 3100 pregnant women and children. Data will be collected by physical examinations, questionnaires, interviews, ultrasound and biological samples. Pregnant women are being assessed at 12, 20 and 32 weeks of gestation to collect information about environmental exposures and fetal growth. The children will be followed until the age of 4 years.. longitudinal cohort study| prenatal exposures| pollution| diet| genetics| study design| biological samples| childhood growth| child development| endocrine disruptors|oxidative stress| polychlorinated-biphenyls| prenatal exposure| arachidonic-acid| air-pollutants| birth-weight| asthma| preeclampsia| supplementation| pregnancy.	SEP-2006	longitudinal cohort study| prenatal exposures| pollution| diet| genetics| study design| biological samples| childhood growth| child development| endocrine disruptors|oxidative stress| polychlorinated-biphenyls| prenatal exposure| arachidonic-acid| air-pollutants| birth-weight| asthma| preeclampsia| supplementation| pregnancy	Ribas-Fito, N; Ramon, R; Ballester, F; Grimalt, J; Marco, A; Olea, N; Posada, M; Rebagliato, M; Tardon, A; Torrent, M; Sunyer, J	Child health and the environment: The INMA spanish study		PAEDIATRIC AND PERINATAL EPIDEMIOLOGY	longitudinal cohort study; prenatal exposures; pollution; diet; genetics; study design; biological samples; childhood growth; child development; endocrine disruptors	OXIDATIVE STRESS; POLYCHLORINATED-BIPHENYLS; PRENATAL EXPOSURE; ARACHIDONIC-ACID; AIR-POLLUTANTS; BIRTH-WEIGHT; ASTHMA; PREECLAMPSIA; SUPPLEMENTATION; PREGNANCY	The INMA (INfancia y Medio Ambiente [Environment and Childhood]) is a population-based cohort study in different Spanish cities, that focuses on prenatal environmental exposures and growth, development and health from early fetal life until childhood. The study focuses on five primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) asthma and allergies; (4) sexual and reproductive development; and (5) environmental exposure pathways. The general aims of the project are: (1) to describe the degree of individual prenatal exposure to environmental pollutants, and the internal dose of chemicals during pregnancy, at birth and during childhood in Spain; (2) to evaluate the impact of the exposure to different contaminants on fetal and infant growth, health and development; (3) to evaluate the role of diet on fetal and infant growth, health and development; and (4) to evaluate the interaction between persistent pollutants, nutrients and genetic determinants on fetal and infant growth, health and development. Extensive assessments will be carried out on 3100 pregnant women and children. Data will be collected by physical examinations, questionnaires, interviews, ultrasound and biological samples. Pregnant women are being assessed at 12, 20 and 32 weeks of gestation to collect information about environmental exposures and fetal growth. The children will be followed until the age of 4 years.	22	89	2006	8	10.1111/j.1365-3016.2006.00745.x	Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics
Accidental ingestions in children with peanut allergy. Background: Accidental exposure to peanut has been reported to occur frequently. Total avoidance of peanut is difficult because of its widespread use, manufacturing and labeling errors, utensil contamination, and label misinterpretation. Objective: Given the apparent increased awareness of peanut allergy by both consumers and food manufacturers, we aimed to determine the current frequency of accidental exposures occurring in peanut allergic children in Quebec and to identify factors associated with exposure. Methods: The parents of children with peanut allergy diagnosed at the Montreal Children's Hospital completed questionnaires about accidental exposure to peanut occurring over the period of the preceding year. Logistic regression was used to identify associated factors. Results: Of 252 children, 62% were boys, with a mean age of 8.1 years (SD, 2.9). The mean age at diagnosis was 2.0 years (SD, 2.1). Thirty-five accidental exposures occurred in 29 children over a period of 244 patient-years, yielding an annual incidence rate of 14.3% (95% CI, 10.0% to 19.9%). Fifteen reactions were mild, 16 moderate, and 4 severe. Of 20 reactions that were moderate to severe, only 4 received epinephrine. Eighty percent of children attended schools prohibiting peanut, and only 1 accidental exposure occurred at school. No associated factors were identified. Conclusion: Accidental exposure to peanut occurs at a lower frequency than previously reported, but most reactions are managed inappropriately. Clinical implications: Enhanced awareness, access to safer environments, and good food manufacturing practices may have contributed to a lower incidence of inadvertent peanut exposure, but a further reduction and better education on allergy management are desirable.. peanut allergy| accidental ingestion| treatment| peanut safe policies|tree-nut-allergy| skin prick tests| natural-history| food allergy| hypersensitivity reactions| anaphylactic reactions| ige concentrations| prevalence| adolescents| resolution.	AUG-2006	peanut allergy| accidental ingestion| treatment| peanut safe policies|tree-nut-allergy| skin prick tests| natural-history| food allergy| hypersensitivity reactions| anaphylactic reactions| ige concentrations| prevalence| adolescents| resolution	Yu, JW; Kagan, R; Verreault, N; Nicolas, N; Joseph, L; Pierre, YS; Clarke, A	Accidental ingestions in children with peanut allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	peanut allergy; accidental ingestion; treatment; peanut safe policies	TREE-NUT-ALLERGY; SKIN PRICK TESTS; NATURAL-HISTORY; FOOD ALLERGY; HYPERSENSITIVITY REACTIONS; ANAPHYLACTIC REACTIONS; IGE CONCENTRATIONS; PREVALENCE; ADOLESCENTS; RESOLUTION	Background: Accidental exposure to peanut has been reported to occur frequently. Total avoidance of peanut is difficult because of its widespread use, manufacturing and labeling errors, utensil contamination, and label misinterpretation. Objective: Given the apparent increased awareness of peanut allergy by both consumers and food manufacturers, we aimed to determine the current frequency of accidental exposures occurring in peanut allergic children in Quebec and to identify factors associated with exposure. Methods: The parents of children with peanut allergy diagnosed at the Montreal Children's Hospital completed questionnaires about accidental exposure to peanut occurring over the period of the preceding year. Logistic regression was used to identify associated factors. Results: Of 252 children, 62% were boys, with a mean age of 8.1 years (SD, 2.9). The mean age at diagnosis was 2.0 years (SD, 2.1). Thirty-five accidental exposures occurred in 29 children over a period of 244 patient-years, yielding an annual incidence rate of 14.3% (95% CI, 10.0% to 19.9%). Fifteen reactions were mild, 16 moderate, and 4 severe. Of 20 reactions that were moderate to severe, only 4 received epinephrine. Eighty percent of children attended schools prohibiting peanut, and only 1 accidental exposure occurred at school. No associated factors were identified. Conclusion: Accidental exposure to peanut occurs at a lower frequency than previously reported, but most reactions are managed inappropriately. Clinical implications: Enhanced awareness, access to safer environments, and good food manufacturing practices may have contributed to a lower incidence of inadvertent peanut exposure, but a further reduction and better education on allergy management are desirable.	46	89	2006	7	10.1016/j.jaci.2006.04.024	Allergy; Immunology
Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation. Increased exposure to air pollutants such as diesel exhaust particles (DEP) has been proposed as one mechanism to explain the rise in allergic disorders. However, the immunologic mechanisms by which DEP enhance allergic sensitization and asthma remain unclear. We hypothesized that DEP act as an adjuvant for immature dendritic cell (DC) maturation via its effect on airway epithelial cell-derived microenvironment for DC. Immature monocyte-derived DC (iMDDC) failed to undergo phenotypic (CD80, CD83, CD86) or functional (T cell activation) maturation in response to exposure to DEP (0.001-100 mu g/ml). In contrast, primary cultures of human bronchial epithelial cells (HBEC) treated with DEP induced iMDDC phenotypic maturation (2.6 +/- 0.1-fold increase in CD83 expression, n = 4, p < 0.05) and functional maturation (2.6 +/- 0.2-fold increase in T cell activation, n = 4, p < 0.05). Functional maturation of iMDDC was induced by conditioned medium derived from DEP-treated HBEC, and was inhibited in cultures with DEP-treated HBEC and blocking Abs against GM-CSF, or GM-CSF-targeted small interfering RNA. These data suggest that DEP induce Ag-independent DC maturation via epithelial cell-DC interactions mediated by HBEC-derived GM-CSF. Although additional signals may be required for polarization of DC, these data suggest a novel mechanism by which environmental pollutants alter airway immune responses.. colony-stimulating factor| ambient particulate matter| regulatory t-cells| gm-csf| inflammatory response| transgene expression| asthma| antigen| sensitization| tolerance.	JUN 15-2006	colony-stimulating factor| ambient particulate matter| regulatory t-cells| gm-csf| inflammatory response| transgene expression| asthma| antigen| sensitization| tolerance	Bleck, B; Tse, DB; Jaspers, I; de Lafaille, MAC; Reibman, J	Diesel exhaust particle-exposed human bronchial epithelial cells induce dendritic cell maturation		JOURNAL OF IMMUNOLOGY		COLONY-STIMULATING FACTOR; AMBIENT PARTICULATE MATTER; REGULATORY T-CELLS; GM-CSF; INFLAMMATORY RESPONSE; TRANSGENE EXPRESSION; ASTHMA; ANTIGEN; SENSITIZATION; TOLERANCE	Increased exposure to air pollutants such as diesel exhaust particles (DEP) has been proposed as one mechanism to explain the rise in allergic disorders. However, the immunologic mechanisms by which DEP enhance allergic sensitization and asthma remain unclear. We hypothesized that DEP act as an adjuvant for immature dendritic cell (DC) maturation via its effect on airway epithelial cell-derived microenvironment for DC. Immature monocyte-derived DC (iMDDC) failed to undergo phenotypic (CD80, CD83, CD86) or functional (T cell activation) maturation in response to exposure to DEP (0.001-100 mu g/ml). In contrast, primary cultures of human bronchial epithelial cells (HBEC) treated with DEP induced iMDDC phenotypic maturation (2.6 +/- 0.1-fold increase in CD83 expression, n = 4, p < 0.05) and functional maturation (2.6 +/- 0.2-fold increase in T cell activation, n = 4, p < 0.05). Functional maturation of iMDDC was induced by conditioned medium derived from DEP-treated HBEC, and was inhibited in cultures with DEP-treated HBEC and blocking Abs against GM-CSF, or GM-CSF-targeted small interfering RNA. These data suggest that DEP induce Ag-independent DC maturation via epithelial cell-DC interactions mediated by HBEC-derived GM-CSF. Although additional signals may be required for polarization of DC, these data suggest a novel mechanism by which environmental pollutants alter airway immune responses.	47	89	2006	7		Immunology
Pathogenesis of COPD. Chronic obstructive pulmonary disease (COPD) is characterized and defined by limitation of expiratory airflow. This can result from several types of anatomical lesions, including loss of lung elastic recoil and fibrosis and narrowing of small airways. Inflammation, edema, and secretions also contribute variably to airflow limitation. Smoking can cause COPD through several mechanisms. First, smoke is a powerful inducer of an inflammatory response. Inflammatory mediators, including oxidants and proteases, are believed to play a major role in causing lung damage. Smoke can also alter lung repair responses in several ways. Inhibition of repair may lead to tissue destruction that characterizes emphysema, whereas abnormal repair can lead to the peribronchiolar fibrosis that causes airflow limitation in small airways. Genetic factors likely play a major role and probably account for much of the heterogeneity susceptibility to smoke and other factors. Many factors may play a role, but to date, only alpha-1 protease inhibitor deficiency has been unambiguously identified. Exposures other than cigarette smoke can contribute to the development of COPD. Inflammation of the lower respiratory tract that results from asthma or other chronic disorders may also contribute to the development of fixed airway obstruction. COPD is not only a disease of the lungs but is also a systemic inflammatory disorder. Muscular weakness, increased risk for atherosclerotic vascular disease, depression, osteoporosis, and abnormalities in fluids and electrolyte balance may all be consequences of COPD. Advances in understanding the pathogenesis of COPD have the potential for identifying new therapeutic targets that could alter the natural history of this devastating disorder.. bronchitis| emphysema| peribronchiolar fibrosis| cigarette smoking| protease| antioxidant| repair|obstructive-pulmonary-disease| necrosis-factor-alpha| growth-factor-beta| bronchoalveolar lavage fluid| bronchial epithelial-cells| collagen gel contraction| fibroblast-mediated contraction| human neutrophil elastase| lower respiratory-tract| human lung fibroblasts.	APR-2005	bronchitis| emphysema| peribronchiolar fibrosis| cigarette smoking| protease| antioxidant| repair|obstructive-pulmonary-disease| necrosis-factor-alpha| growth-factor-beta| bronchoalveolar lavage fluid| bronchial epithelial-cells| collagen gel contraction| fibroblast-mediated contraction| human neutrophil elastase| lower respiratory-tract| human lung fibroblasts	Spurzem, JR; Rennard, SI	Pathogenesis of COPD		SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE	bronchitis; emphysema; peribronchiolar fibrosis; cigarette smoking; protease; antioxidant; repair	OBSTRUCTIVE-PULMONARY-DISEASE; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; BRONCHOALVEOLAR LAVAGE FLUID; BRONCHIAL EPITHELIAL-CELLS; COLLAGEN GEL CONTRACTION; FIBROBLAST-MEDIATED CONTRACTION; HUMAN NEUTROPHIL ELASTASE; LOWER RESPIRATORY-TRACT; HUMAN LUNG FIBROBLASTS	Chronic obstructive pulmonary disease (COPD) is characterized and defined by limitation of expiratory airflow. This can result from several types of anatomical lesions, including loss of lung elastic recoil and fibrosis and narrowing of small airways. Inflammation, edema, and secretions also contribute variably to airflow limitation. Smoking can cause COPD through several mechanisms. First, smoke is a powerful inducer of an inflammatory response. Inflammatory mediators, including oxidants and proteases, are believed to play a major role in causing lung damage. Smoke can also alter lung repair responses in several ways. Inhibition of repair may lead to tissue destruction that characterizes emphysema, whereas abnormal repair can lead to the peribronchiolar fibrosis that causes airflow limitation in small airways. Genetic factors likely play a major role and probably account for much of the heterogeneity susceptibility to smoke and other factors. Many factors may play a role, but to date, only alpha-1 protease inhibitor deficiency has been unambiguously identified. Exposures other than cigarette smoke can contribute to the development of COPD. Inflammation of the lower respiratory tract that results from asthma or other chronic disorders may also contribute to the development of fixed airway obstruction. COPD is not only a disease of the lungs but is also a systemic inflammatory disorder. Muscular weakness, increased risk for atherosclerotic vascular disease, depression, osteoporosis, and abnormalities in fluids and electrolyte balance may all be consequences of COPD. Advances in understanding the pathogenesis of COPD have the potential for identifying new therapeutic targets that could alter the natural history of this devastating disorder.	166	89	2005	12	10.1055/s-2005-869535	General & Internal Medicine; Respiratory System
Rethinking race/ethnicity, income, and childhood asthma: Racial/ethnic disparities concentrated among the very poor. Objective. Past studies of the prevalence of childhood asthma have yielded conflicting findings as to whether racial/ethnic disparities remain after other factors such as, income, are taken into account. The objective of this study was to examine the association of race/ethnicity and family income with the prevalence of childhood asthma and to assess whether racial/ethnic disparities vary by income strata. Methods. Cross-sectional data on 14,244 children aged < 18 years old in the 1997 National Health Interview Survey were examined. The authors used logistic regression to analyze the independent and joint effects of race/ethnicity and income-to-federal poverty level (FPL) ratio, adjusting for demographic covariates. The main outcome measure was parental report of the child having ever been diagnosed with asthma. Results. Bivariate analyses, based on weighted percentages, revealed that asthma was more prevalent among non-Hispanic black children (13.6%) than among non-Hispanic white children (11.2%; p < 0.01), but the prevalence of asthma did not differ significantly between Hispanic children (10.1%) and non-Hispanic white children (11.2%; p = 0.13). Overall, non-Hispanic black children were at higher risk for asthma than non-Hispanic white children (adjusted odds ratio [OR]= 1.20; 95% confidence interval [CI] 1.03, 1.40), after adjustment for sociodemographic variables, including the ratio of annual family income to the FPL. Asthma prevalence did not differ between Hispanic children and non-Hispanic white children in adjusted analyses (adjusted OR = 0.85; 95% CI 0.71, 1.02). Analyses stratified by income revealed that only among children from families with incomes less than half the FPL did non-Hispanic black children have a higher risk of asthma than non-Hispanic white children (adjusted OR = 1.99; 95% CI 1.09, 3.64). No black vs. white differences existed at other income levels. Subsequent analyses of these very poor children that took into account additional potentially explanatory variables did not attenuate the higher asthma risk for very poor non-Hispanic black children relative to very poor non-Hispanic white children. Conclusions. Non-Hispanic black children were at substantially higher risk of asthma than non-Hispanic white children only among the very poor. The concentration of racial/ethnic differences only among the very poor suggests that patterns of social and environmental exposures must overshadow any hypothetical genetic risk.. inner-city children| socioeconomic-status| pediatric asthma| indoor allergens| medication-use| risk-factors| management-practices| cockroach allergen| ethnic-differences| health-services.	MAR-APR-2005	inner-city children| socioeconomic-status| pediatric asthma| indoor allergens| medication-use| risk-factors| management-practices| cockroach allergen| ethnic-differences| health-services	Smith, LA; Hatcher-Ross, JL; Wertheimer, R; Kahn, RS	Rethinking race/ethnicity, income, and childhood asthma: Racial/ethnic disparities concentrated among the very poor		PUBLIC HEALTH REPORTS		INNER-CITY CHILDREN; SOCIOECONOMIC-STATUS; PEDIATRIC ASTHMA; INDOOR ALLERGENS; MEDICATION-USE; RISK-FACTORS; MANAGEMENT-PRACTICES; COCKROACH ALLERGEN; ETHNIC-DIFFERENCES; HEALTH-SERVICES	Objective. Past studies of the prevalence of childhood asthma have yielded conflicting findings as to whether racial/ethnic disparities remain after other factors such as, income, are taken into account. The objective of this study was to examine the association of race/ethnicity and family income with the prevalence of childhood asthma and to assess whether racial/ethnic disparities vary by income strata. Methods. Cross-sectional data on 14,244 children aged < 18 years old in the 1997 National Health Interview Survey were examined. The authors used logistic regression to analyze the independent and joint effects of race/ethnicity and income-to-federal poverty level (FPL) ratio, adjusting for demographic covariates. The main outcome measure was parental report of the child having ever been diagnosed with asthma. Results. Bivariate analyses, based on weighted percentages, revealed that asthma was more prevalent among non-Hispanic black children (13.6%) than among non-Hispanic white children (11.2%; p < 0.01), but the prevalence of asthma did not differ significantly between Hispanic children (10.1%) and non-Hispanic white children (11.2%; p = 0.13). Overall, non-Hispanic black children were at higher risk for asthma than non-Hispanic white children (adjusted odds ratio [OR]= 1.20; 95% confidence interval [CI] 1.03, 1.40), after adjustment for sociodemographic variables, including the ratio of annual family income to the FPL. Asthma prevalence did not differ between Hispanic children and non-Hispanic white children in adjusted analyses (adjusted OR = 0.85; 95% CI 0.71, 1.02). Analyses stratified by income revealed that only among children from families with incomes less than half the FPL did non-Hispanic black children have a higher risk of asthma than non-Hispanic white children (adjusted OR = 1.99; 95% CI 1.09, 3.64). No black vs. white differences existed at other income levels. Subsequent analyses of these very poor children that took into account additional potentially explanatory variables did not attenuate the higher asthma risk for very poor non-Hispanic black children relative to very poor non-Hispanic white children. Conclusions. Non-Hispanic black children were at substantially higher risk of asthma than non-Hispanic white children only among the very poor. The concentration of racial/ethnic differences only among the very poor suggests that patterns of social and environmental exposures must overshadow any hypothetical genetic risk.	70	89	2005	8		Public, Environmental & Occupational Health
Impulse oscillometry provides an effective measure of lung dysfunction in 4-year-old children at risk for persistent asthma. Background: Objective lung function measurements are routinely used to diagnose and manage asthma, but their utility for young children has not been defined. Objective: Bronchodilator responses were measured by means of impulse oscillometry (IOS) and compared with conventional spirometry to determine the value of lung function measures in 4-year-old asthma-prone children. Methods: The study participants were in the Childhood Asthma Prevention Study (National Institute of Health/National Institute of Allergy and Infectious Diseases) and at risk for asthma. At age 4 years, concurrent asthma was determined by using a previously validated modified American Thoracic Society questionnaire. Children performed IOS and spirometry before and after albuterol administration and underwent skin prick testing to 13 common allergens to assess atopy. IOS measures were as follows: airways resistance at 5 Hz and 10 Hz, airways reactance at 5 Hz and 10 Hz, and resonant frequency. Results: Asthmatic patients versus nonasthmatic patients significantly differed in their IOS-assessed bronchodilator responses through Delta resistance at 5 Hz (medians, 27% vs 17%; P = .02) and Delta resistance at 10 Hz (24% vs 16%; P = .03). Because atopic children who have frequent wheezing are at risk for persistent asthma, the data were analyzed in regard to atopic patients with or without asthma. IOS strongly distinguished atopic asthmatic children through A resistance at 5 Hz (36% vs 13 %, P = .007), Delta resistance at 10 Hz (25% vs 11%, P = .02), and Delta reactance at 10 Hz (47 % vs 12 %, P = .03). Conventional spirometry did not establish similar statistically significant findings. Conclusion: IOS bronchodilator responses are remarkably abnormal in 4-year-old children, who are most likely to have persistent asthma. IOS is a useful diagnostic tool in early asthma development and might be a helpful objective outcome measure of early interventions.. asthma| atopy| children| early intervention| lung function| bronchodilator response| impulse oscillometry| spirometry|forced oscillation technique| childhood asthma| airway-obstruction| methacholine responsiveness| interrupter technique| respiratory symptoms| preschool-children| young-children| peak flow| cold-air.	AUG-2003	asthma| atopy| children| early intervention| lung function| bronchodilator response| impulse oscillometry| spirometry|forced oscillation technique| childhood asthma| airway-obstruction| methacholine responsiveness| interrupter technique| respiratory symptoms| preschool-children| young-children| peak flow| cold-air	Marotta, A; Klinnert, MD; Price, MR; Larsen, GL; Liu, AH	Impulse oscillometry provides an effective measure of lung dysfunction in 4-year-old children at risk for persistent asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; atopy; children; early intervention; lung function; bronchodilator response; impulse oscillometry; spirometry	FORCED OSCILLATION TECHNIQUE; CHILDHOOD ASTHMA; AIRWAY-OBSTRUCTION; METHACHOLINE RESPONSIVENESS; INTERRUPTER TECHNIQUE; RESPIRATORY SYMPTOMS; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; PEAK FLOW; COLD-AIR	Background: Objective lung function measurements are routinely used to diagnose and manage asthma, but their utility for young children has not been defined. Objective: Bronchodilator responses were measured by means of impulse oscillometry (IOS) and compared with conventional spirometry to determine the value of lung function measures in 4-year-old asthma-prone children. Methods: The study participants were in the Childhood Asthma Prevention Study (National Institute of Health/National Institute of Allergy and Infectious Diseases) and at risk for asthma. At age 4 years, concurrent asthma was determined by using a previously validated modified American Thoracic Society questionnaire. Children performed IOS and spirometry before and after albuterol administration and underwent skin prick testing to 13 common allergens to assess atopy. IOS measures were as follows: airways resistance at 5 Hz and 10 Hz, airways reactance at 5 Hz and 10 Hz, and resonant frequency. Results: Asthmatic patients versus nonasthmatic patients significantly differed in their IOS-assessed bronchodilator responses through Delta resistance at 5 Hz (medians, 27% vs 17%; P = .02) and Delta resistance at 10 Hz (24% vs 16%; P = .03). Because atopic children who have frequent wheezing are at risk for persistent asthma, the data were analyzed in regard to atopic patients with or without asthma. IOS strongly distinguished atopic asthmatic children through A resistance at 5 Hz (36% vs 13 %, P = .007), Delta resistance at 10 Hz (25% vs 11%, P = .02), and Delta reactance at 10 Hz (47 % vs 12 %, P = .03). Conventional spirometry did not establish similar statistically significant findings. Conclusion: IOS bronchodilator responses are remarkably abnormal in 4-year-old children, who are most likely to have persistent asthma. IOS is a useful diagnostic tool in early asthma development and might be a helpful objective outcome measure of early interventions.	37	89	2003	6	10.1067/mai.2003.1627	Allergy; Immunology
Reduced transforming growth factor-beta 1-producing T cells in the duodenal mucosa of children with food allergy. Infant food allergies are increasing, and many breast-fed infants now sensitize to maternally-ingested antigens. As low-dose oral tolerance requires generation of suppressor lymphocytes producing TGF-beta1 (Th3 cells), we studied these cells in duodenal biopsies after diagnostic endoscopy. Spontaneous production of Th1, Th2 and Th3 cytokines by duodenal lymphocytes was studied using flow cytometry in 20 children with no eventual clinicopathological diagnosis (controls), 30 children with multiple food allergy, nine with celiac disease and six with inflammatory enteropathies. Immunohistochemistry and in situ hybridization were used to localize TGF-beta1 protein and mRNA in matched biopsies. We found no significant Th1/Th2 skewing amongst mucosal lymphocytes in allergic children compared to controls, although celiac and inflammatory enteropathy patients showed increased Th1 responses. By contrast, the allergic children showed reduction of TGF-beta1(+) lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF-beta1 expression was also seen in mononuclear cells and epithelium in food allergy by immunohistochemistry and in situ hybridization. The dominant mucosal abnormality in food allergic children was, thus, not Th2 deviation but impaired generation of Th3 cells. As generation of these cells requires innate immune response to enteric bacteria, we suggest that changing infectious exposures may inhibit primary establishment of basic oral tolerance mechanisms.. food allergy| lymphocytes| tgf-beta| celiac disease|inflammatory-bowel-disease| atopic disease| expression| beta| probiotics| induction| immunity| infants| antigen| protein.	AUG-2003	food allergy| lymphocytes| tgf-beta| celiac disease|inflammatory-bowel-disease| atopic disease| expression| beta| probiotics| induction| immunity| infants| antigen| protein	Perez-Machado, MA; Ashwood, P; Thomson, MA; Latcham, F; Sim, R; Walker-Smith, JA; Murch, SH	Reduced transforming growth factor-beta 1-producing T cells in the duodenal mucosa of children with food allergy		EUROPEAN JOURNAL OF IMMUNOLOGY	food allergy; lymphocytes; TGF-beta; celiac disease	INFLAMMATORY-BOWEL-DISEASE; ATOPIC DISEASE; EXPRESSION; BETA; PROBIOTICS; INDUCTION; IMMUNITY; INFANTS; ANTIGEN; PROTEIN	Infant food allergies are increasing, and many breast-fed infants now sensitize to maternally-ingested antigens. As low-dose oral tolerance requires generation of suppressor lymphocytes producing TGF-beta1 (Th3 cells), we studied these cells in duodenal biopsies after diagnostic endoscopy. Spontaneous production of Th1, Th2 and Th3 cytokines by duodenal lymphocytes was studied using flow cytometry in 20 children with no eventual clinicopathological diagnosis (controls), 30 children with multiple food allergy, nine with celiac disease and six with inflammatory enteropathies. Immunohistochemistry and in situ hybridization were used to localize TGF-beta1 protein and mRNA in matched biopsies. We found no significant Th1/Th2 skewing amongst mucosal lymphocytes in allergic children compared to controls, although celiac and inflammatory enteropathy patients showed increased Th1 responses. By contrast, the allergic children showed reduction of TGF-beta1(+) lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF-beta1 expression was also seen in mononuclear cells and epithelium in food allergy by immunohistochemistry and in situ hybridization. The dominant mucosal abnormality in food allergic children was, thus, not Th2 deviation but impaired generation of Th3 cells. As generation of these cells requires innate immune response to enteric bacteria, we suggest that changing infectious exposures may inhibit primary establishment of basic oral tolerance mechanisms.	33	89	2003	9	10.1002/eji.200323308	Immunology
Fungal levels in the home and lower respiratory tract illnesses in the first year of life. The association between home dampness and lower respiratory symptoms in children has been well documented. Whether fungal exposures contribute to this association is uncertain. In a prospective birth cohort of 499 children of parents with asthma/allergies, we examined in-home fungal concentrations as predictors of lower respiratory illnesses (LRI) (croup, pneumonia, bronchitis, and bronchiolitis) in the first year. In multivariate analyses, we found a significant increased relative risk (RR) between LRI and high levels (more than the 90th percentile) of airborne Penicillium (RR = 1.73, 95% confidence interval [CI], 1.23, 2.43), dust-borne Clodosporium (RR = 1.52; Cl, 1.02, 2.25), Zygornycetes (RR = 1.96; CI, 1.35, 2.83), and Alternaria (RR = 1.51; CI, 1.00, 2.28), after controlling for sex, presence of water damage or visible mold/mildew, born in winter, breastfeeding, and being exposed to other children through siblings. In a multivariate analysis, the RR of LRI was elevated in households with any fungal level at more than the 90th percentile (RR = 1.86; CI, 1.21, 2.88). Exposure to high fungal levels increased the risk of LRI in infancy, even for infants with nonwheezing LRI. Actual mechanisms remain unknown, but fungi and their components (glucans, mycotoxins, and proteins) may increase the risk of LRI by acting as irritants or through increasing susceptibility to infection.. fungi| respiratory tract infections| infants| public health|indoor allergen levels| childhood asthma| children| dampness| health| spores| associations| predictors| activation| diseases.	JUL 15-2003	fungi| respiratory tract infections| infants| public health|indoor allergen levels| childhood asthma| children| dampness| health| spores| associations| predictors| activation| diseases	Stark, PC; Burge, HA; Ryan, LM; Milton, DK; Gold, DR	Fungal levels in the home and lower respiratory tract illnesses in the first year of life		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	fungi; respiratory tract infections; infants; public health	INDOOR ALLERGEN LEVELS; CHILDHOOD ASTHMA; CHILDREN; DAMPNESS; HEALTH; SPORES; ASSOCIATIONS; PREDICTORS; ACTIVATION; DISEASES	The association between home dampness and lower respiratory symptoms in children has been well documented. Whether fungal exposures contribute to this association is uncertain. In a prospective birth cohort of 499 children of parents with asthma/allergies, we examined in-home fungal concentrations as predictors of lower respiratory illnesses (LRI) (croup, pneumonia, bronchitis, and bronchiolitis) in the first year. In multivariate analyses, we found a significant increased relative risk (RR) between LRI and high levels (more than the 90th percentile) of airborne Penicillium (RR = 1.73, 95% confidence interval [CI], 1.23, 2.43), dust-borne Clodosporium (RR = 1.52; Cl, 1.02, 2.25), Zygornycetes (RR = 1.96; CI, 1.35, 2.83), and Alternaria (RR = 1.51; CI, 1.00, 2.28), after controlling for sex, presence of water damage or visible mold/mildew, born in winter, breastfeeding, and being exposed to other children through siblings. In a multivariate analysis, the RR of LRI was elevated in households with any fungal level at more than the 90th percentile (RR = 1.86; CI, 1.21, 2.88). Exposure to high fungal levels increased the risk of LRI in infancy, even for infants with nonwheezing LRI. Actual mechanisms remain unknown, but fungi and their components (glucans, mycotoxins, and proteins) may increase the risk of LRI by acting as irritants or through increasing susceptibility to infection.	31	89	2003	6	10.1164/rccm.200207-730OC	General & Internal Medicine; Respiratory System
Schistosoma mansoni infection is associated with a reduced course of asthma. Background: Helminthic infections decrease skin reactivity to indoor allergens, but data on whether they influence asthma severity are lacking. Objective: This study evaluated the course of asthma in patients with and without Schistosoma mansoni infection. Methods: Asthmatic subjects were enrolled from 3 low-socioeconomic areas: a rural area endemic for schistosomiasis (group 1) in addition to a rural area (group 2) and a slum area (group 3), both of which were not endemic for schistosomiasis. A questionnaire on the basis of the International Study of Asthma and Allergies in Childhood study was applied in these 3 areas, and from each area, 21 age- and sex-matched asthmatic subjects were selected for a prospective 1-year study. Pulmonary function tests, skin prick tests with indoor allergens, stool examinations, and serum evaluations were performed in these subjects. Every 3 months, the subjects were evaluated for asthma exacerbation through physical examination, and a questionnaire regarding asthma symptoms and use of antiasthma medicine was administered. Results: The prevalence of S mansoni infection was greater in group I compared with in groups 2 and 3 (P < .0001), whereas the frequency of other helminth and protozoa infections was similar among the 3 groups. The frequency of positive skin test responses to indoor allergens was less (19.0%) in group I subjects relative to those in group 2 (76.2%) and group 3 (57.1%; P < .001). The frequencies of symptoms, use of antiasthma drugs, and pulmonary abnormal findings at physical examination were less in group 1 subjects than in group 2 and 3 subjects (P = .0001). Conclusion: Our results suggest that S mansoni infection is associated with a milder course of asthma.. asthma| skin prick test| dust mites| helminths| schistosoma mansoni| il-10| ige|inverse association| atopy| reactivity| exposure| activation| allergens| children| il-10.	MAY-2003	asthma| skin prick test| dust mites| helminths| schistosoma mansoni| il-10| ige|inverse association| atopy| reactivity| exposure| activation| allergens| children| il-10	Medeiros, M; Figueiredo, JP; Almeida, MC; Matos, MA; Araujo, MI; Cruz, AA; Atta, AM; Rego, MAV; de Jesus, AR; Taketomi, EA; Carvalho, EM	Schistosoma mansoni infection is associated with a reduced course of asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; skin prick test; dust mites; helminths; Schistosoma mansoni; IL-10; IgE	INVERSE ASSOCIATION; ATOPY; REACTIVITY; EXPOSURE; ACTIVATION; ALLERGENS; CHILDREN; IL-10	Background: Helminthic infections decrease skin reactivity to indoor allergens, but data on whether they influence asthma severity are lacking. Objective: This study evaluated the course of asthma in patients with and without Schistosoma mansoni infection. Methods: Asthmatic subjects were enrolled from 3 low-socioeconomic areas: a rural area endemic for schistosomiasis (group 1) in addition to a rural area (group 2) and a slum area (group 3), both of which were not endemic for schistosomiasis. A questionnaire on the basis of the International Study of Asthma and Allergies in Childhood study was applied in these 3 areas, and from each area, 21 age- and sex-matched asthmatic subjects were selected for a prospective 1-year study. Pulmonary function tests, skin prick tests with indoor allergens, stool examinations, and serum evaluations were performed in these subjects. Every 3 months, the subjects were evaluated for asthma exacerbation through physical examination, and a questionnaire regarding asthma symptoms and use of antiasthma medicine was administered. Results: The prevalence of S mansoni infection was greater in group I compared with in groups 2 and 3 (P < .0001), whereas the frequency of other helminth and protozoa infections was similar among the 3 groups. The frequency of positive skin test responses to indoor allergens was less (19.0%) in group I subjects relative to those in group 2 (76.2%) and group 3 (57.1%; P < .001). The frequencies of symptoms, use of antiasthma drugs, and pulmonary abnormal findings at physical examination were less in group 1 subjects than in group 2 and 3 subjects (P = .0001). Conclusion: Our results suggest that S mansoni infection is associated with a milder course of asthma.	28	89	2003	5	10.1067/mai.2003.1381	Allergy; Immunology
Genetic susceptibility to food allergy is linked to differential T(H)2-T(H)1 responses in C3H/HeJ and BALB/c mice. Background: Although food allergy is a serious health problem in westernized countries, factors influencing the development of food allergy are largely unknown. Appropriate marine models of food allergy would be useful in understanding the mechanisms underlying food allergy in human subjects. Objective: We sought to determine the susceptibility of different strains of mice to food hypersensitivity. Methods: C3H/HeJ and BALB/c mice were sensitized to cow's milk (CM) or peanut by means of intragastric administration, with cholera toxin as a mucosal adjuvant. Mice were then challenged with CM or peanut Antigen-specific IgE levels, anaphylactic symptoms, plasma histamine levels, and splenocyte cytokine profiles of these 2 strains were compared. Results: CM-specific IgE levels were significantly increased only in the C3HMeJ strain, 87% of which exhibited systemic anaphylactic reactions accompanied by significantly increased plasma histamine levels in response to challenge. BALB/c mice exhibited no significant CM-specific IgE response, increased plasma histamine levels, or anaphylactic symptoms. After peanut challenge, 100% of peanut-sensitized C3H/HeJ mice exhibited high levels of peanut-specific IgE and anaphylactic symptoms. In contrast, no hypersensitivity reactions were detected in BALB/c mice, despite the presence of significant serum peanut-specific IgE levels. Splenocytes from CM- and peanut-sensitized C3H/HeJ mice exhibited significantly increased IL-4 and IL-10 secretion, whereas splenocytes from BALB/c mice exhibited significantly increased IFN-gamma secretion. Conclusion: induction of food-induced hypersensitivity reactions in mice is strain dependent, with C3H/HeJ mice being susceptible and BALB/c mice being resistant. This strain-dependent susceptibility to food allergy is associated with differential T(H)2-T(H)1 responses after intragastric food allergen sensitization.. marine strains| food allergy susceptibility| t(h)2-t(h)1 cytokines|major peanut allergen| house-dust endotoxin| t-cell| ifn-gamma| murine model| atopic-dermatitis| immune-responses| interferon-gamma| oral tolerance| il-10.	MAY-2003	marine strains| food allergy susceptibility| t(h)2-t(h)1 cytokines|major peanut allergen| house-dust endotoxin| t-cell| ifn-gamma| murine model| atopic-dermatitis| immune-responses| interferon-gamma| oral tolerance| il-10	Morafo, V; Srivastava, K; Huang, CK; Kleiner, G; Lee, SY; Sampson, HA; Li, XM	Genetic susceptibility to food allergy is linked to differential T(H)2-T(H)1 responses in C3H/HeJ and BALB/c mice		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	marine strains; food allergy susceptibility; T(H)2-T(H)1 cytokines	MAJOR PEANUT ALLERGEN; HOUSE-DUST ENDOTOXIN; T-CELL; IFN-GAMMA; MURINE MODEL; ATOPIC-DERMATITIS; IMMUNE-RESPONSES; INTERFERON-GAMMA; ORAL TOLERANCE; IL-10	Background: Although food allergy is a serious health problem in westernized countries, factors influencing the development of food allergy are largely unknown. Appropriate marine models of food allergy would be useful in understanding the mechanisms underlying food allergy in human subjects. Objective: We sought to determine the susceptibility of different strains of mice to food hypersensitivity. Methods: C3H/HeJ and BALB/c mice were sensitized to cow's milk (CM) or peanut by means of intragastric administration, with cholera toxin as a mucosal adjuvant. Mice were then challenged with CM or peanut Antigen-specific IgE levels, anaphylactic symptoms, plasma histamine levels, and splenocyte cytokine profiles of these 2 strains were compared. Results: CM-specific IgE levels were significantly increased only in the C3HMeJ strain, 87% of which exhibited systemic anaphylactic reactions accompanied by significantly increased plasma histamine levels in response to challenge. BALB/c mice exhibited no significant CM-specific IgE response, increased plasma histamine levels, or anaphylactic symptoms. After peanut challenge, 100% of peanut-sensitized C3H/HeJ mice exhibited high levels of peanut-specific IgE and anaphylactic symptoms. In contrast, no hypersensitivity reactions were detected in BALB/c mice, despite the presence of significant serum peanut-specific IgE levels. Splenocytes from CM- and peanut-sensitized C3H/HeJ mice exhibited significantly increased IL-4 and IL-10 secretion, whereas splenocytes from BALB/c mice exhibited significantly increased IFN-gamma secretion. Conclusion: induction of food-induced hypersensitivity reactions in mice is strain dependent, with C3H/HeJ mice being susceptible and BALB/c mice being resistant. This strain-dependent susceptibility to food allergy is associated with differential T(H)2-T(H)1 responses after intragastric food allergen sensitization.	47	89	2003	7	10.1067/mai.2003.1463	Allergy; Immunology
Basophils express a type 2 cytokine profile on exposure to proteases from helminths and house dust mites. The proteolytic activities frequently associated with sources of allergens and parasite secretions have been suggested as important immunomodulators. We have investigated whether the protease activity of the house dust mite allergen Der p1. and the secreted proteases of the hookworm Necator americanus are able to directly induce type 2 cytokine production by basophils. Der p1 and the secretions of N. americanus induced interleukin (IL)-4, IL-5, and IL-13 but not interferon-gamma mRNA in KU812 basophils. Enzyme-linked immunosorbent assay confirmed that IL-4 and IL-13 were secreted. A nonproteolytic antigen failed to induce cytokine expression, and preincubation of Der p1. or N. americanus secretions with protease inhibitors inhibited cytokine expression. Data were confirmed using basophils purified from human peripheral blood. We speculate that this innate mechanism may contribute to the development of a cytokine milieu that could promote immunoglobulin E synthesis, eosinophil recruitment, and the development of type 2 T cells.. hookworm| allergy| dermatophagoides pteronyssinus|peripheral-blood basophils| der-p-i| activated receptors| enzymatic-activity| tight junctions| il-4 production| allergen| interleukin-4| release| ige.	JAN-2003	hookworm| allergy| dermatophagoides pteronyssinus|peripheral-blood basophils| der-p-i| activated receptors| enzymatic-activity| tight junctions| il-4 production| allergen| interleukin-4| release| ige	Phillips, C; Coward, WR; Pritchard, DI; Hewitt, CRA	Basophils express a type 2 cytokine profile on exposure to proteases from helminths and house dust mites		JOURNAL OF LEUKOCYTE BIOLOGY	hookworm; allergy; Dermatophagoides pteronyssinus	PERIPHERAL-BLOOD BASOPHILS; DER-P-I; ACTIVATED RECEPTORS; ENZYMATIC-ACTIVITY; TIGHT JUNCTIONS; IL-4 PRODUCTION; ALLERGEN; INTERLEUKIN-4; RELEASE; IGE	The proteolytic activities frequently associated with sources of allergens and parasite secretions have been suggested as important immunomodulators. We have investigated whether the protease activity of the house dust mite allergen Der p1. and the secreted proteases of the hookworm Necator americanus are able to directly induce type 2 cytokine production by basophils. Der p1 and the secretions of N. americanus induced interleukin (IL)-4, IL-5, and IL-13 but not interferon-gamma mRNA in KU812 basophils. Enzyme-linked immunosorbent assay confirmed that IL-4 and IL-13 were secreted. A nonproteolytic antigen failed to induce cytokine expression, and preincubation of Der p1. or N. americanus secretions with protease inhibitors inhibited cytokine expression. Data were confirmed using basophils purified from human peripheral blood. We speculate that this innate mechanism may contribute to the development of a cytokine milieu that could promote immunoglobulin E synthesis, eosinophil recruitment, and the development of type 2 T cells.	37	89	2003	7	10.1189/jlb.0702356	Cell Biology; Hematology; Immunology
Changes in serum pneumoproteins caused by short-term exposures to nitrogen trichloride in indoor chlorinated swimming pools. Nitrogen trichloride (NCl3) is an irritant gas released in the air of indoor pools sanitized with chlorine-based disinfectants. In the present study we investigated the effects of NCl3 on the pulmonary epithelium of pool attendees by measuring the leakage into serum of three lung-specific proteins (pneumoproteins): the alveolar surfactant-associated proteins A and B (SP-A and SP-B) and the bronchiolar 16 kDa Clara cell protein (CC16). These pneumoproteins were measured in the serum of 29 recreational swimmers (16 children and 13 adults) before and after attending a chlorinated pool with a mean NCl3 concentration of 490 mug m(-3). Pneumoprotein changes in serum were also studied in 14 trained swimmers performing an intensive 45 min standardized swimming session in a chlorinated pool (mean NCl3 concentration of 355 mug m(-1)) and for the purposes of comparison in a non-chlorinated pool sanitized by the copper silver method. Serum CC16 was not increased in recreational swimmers, but in trained swimmers serum levels of this protein peaked immediately after strenuous exercise, both in the copper/silver pool and in the chlorinated pool. This acute increase in airway permeability is probably the consequence of the mechanical stress on the epithelial barrier caused by overinflation and, or hyperventilation during intense exercise. Serum levels of SP-A and SP-B were unaffected by strenuous exercise in the copper silver pool. The two proteins were, however, significantly increased in a time-dependent manner in recreational and trained swimmers attending the chlorinated pool. The intravascular leakage of SP-A and SP-B was already statistically significant after only 1 h of exposure to pool air without exercising and remained elevated for 12 h after. These changes were knot associated with decrements in lung function. The ability of NCl3 to acutely disrupt the lung epithelium barrier was confirmed in mice using serum CC16 and plasma proteins in bronchoalveolar lavage fluid as permeability markers. The significance of these permeability changes induced by NCl3 in the deep lung is presently unknown. In view of the increasing and widespread human exposure to this gas not only in indoor pools but also in a variety of other situations, these findings warrant further study.. nitrogen trichloride| exercise| pneumoproteins| swimming| lung epithelium| clara cell protein| surfactant-associated proteins| chlorine-based disinfectants| chlorine|clara cell protein| bronchial responsiveness| respiratory symptoms| failure| barrier| asthma| injury| ozone| gas.	NOV-DEC-2002	nitrogen trichloride| exercise| pneumoproteins| swimming| lung epithelium| clara cell protein| surfactant-associated proteins| chlorine-based disinfectants| chlorine|clara cell protein| bronchial responsiveness| respiratory symptoms| failure| barrier| asthma| injury| ozone| gas	Carbonnelle, S; Francaux, M; Doyle, I; Dumont, X; De Burbure, C; Morel, G; Michel, O; Bernard, A	Changes in serum pneumoproteins caused by short-term exposures to nitrogen trichloride in indoor chlorinated swimming pools		BIOMARKERS	nitrogen trichloride; exercise; pneumoproteins; swimming; lung epithelium; Clara cell protein; surfactant-associated proteins; chlorine-based disinfectants; chlorine	CLARA CELL PROTEIN; BRONCHIAL RESPONSIVENESS; RESPIRATORY SYMPTOMS; FAILURE; BARRIER; ASTHMA; INJURY; OZONE; GAS	Nitrogen trichloride (NCl3) is an irritant gas released in the air of indoor pools sanitized with chlorine-based disinfectants. In the present study we investigated the effects of NCl3 on the pulmonary epithelium of pool attendees by measuring the leakage into serum of three lung-specific proteins (pneumoproteins): the alveolar surfactant-associated proteins A and B (SP-A and SP-B) and the bronchiolar 16 kDa Clara cell protein (CC16). These pneumoproteins were measured in the serum of 29 recreational swimmers (16 children and 13 adults) before and after attending a chlorinated pool with a mean NCl3 concentration of 490 mug m(-3). Pneumoprotein changes in serum were also studied in 14 trained swimmers performing an intensive 45 min standardized swimming session in a chlorinated pool (mean NCl3 concentration of 355 mug m(-1)) and for the purposes of comparison in a non-chlorinated pool sanitized by the copper silver method. Serum CC16 was not increased in recreational swimmers, but in trained swimmers serum levels of this protein peaked immediately after strenuous exercise, both in the copper/silver pool and in the chlorinated pool. This acute increase in airway permeability is probably the consequence of the mechanical stress on the epithelial barrier caused by overinflation and, or hyperventilation during intense exercise. Serum levels of SP-A and SP-B were unaffected by strenuous exercise in the copper silver pool. The two proteins were, however, significantly increased in a time-dependent manner in recreational and trained swimmers attending the chlorinated pool. The intravascular leakage of SP-A and SP-B was already statistically significant after only 1 h of exposure to pool air without exercising and remained elevated for 12 h after. These changes were knot associated with decrements in lung function. The ability of NCl3 to acutely disrupt the lung epithelium barrier was confirmed in mice using serum CC16 and plasma proteins in bronchoalveolar lavage fluid as permeability markers. The significance of these permeability changes induced by NCl3 in the deep lung is presently unknown. In view of the increasing and widespread human exposure to this gas not only in indoor pools but also in a variety of other situations, these findings warrant further study.	35	89	2002	15	10.1080/13547500210166612	Biotechnology & Applied Microbiology; Toxicology
New frontiers in CT imaging of airway disease. Combining helical volumetric CT acquisition and thin-slice thickness during breath hold provides an accurate assessment of both focal and diffuse airway diseases. With multiple detector rows, compared with single-slice helical CT, multislice CT can cover a greater volume, during a simple breath hold, and with better longitudinal and in-plane spatial resolution and improved temporal resolution. The result in data set allows the generation of superior multiplanar and 3D images of the airways, including those obtained from techniques developed specifically for airway imaging, such as virtual bronchography and virtual bronchoscopy. Complementary CT evaluation at suspended or continuous full expiration is mandatory to detect air trapping that is a key finding for depicting an obstruction on the small airways. Indications for CT evaluation of the airways include: (a) detection of endobronchial lesions in patients with an unexplained hemoptysis; (b) evaluation of extent of tracheobronchial stenosis for planning treatment and follow-up; (c) detection of congenital airway anomalies revealed by hemoptysis or recurrent infection; (d) detection of postinfectious or postoperative airway fistula or dehiscence, and (e) diagnosis and assessment of extent of bronchiectasis and small airway disease. Improvement in image analysis technique and the use of spirometrically control Of lung Volume acquisition have made possible accurate and reproducible quantitative assessment of airway wall and lumen areas and lung density. This contributes to better insights in physiopathology of obstructive lung disease, particularly in chronic obstructive pulmonary disease and asthma.. chronic obstructive pulmonary disease| airways| helical ct| 3d images|thin-section ct| resolution computed-tomography| pulmonary-function tests| diffuse aspiration bronchiolitis| expiratory ct| spiral ct| tracheobronchial tree| lung transplantation| virtual bronchoscopy| helical ct.	MAY-2002	chronic obstructive pulmonary disease| airways| helical ct| 3d images|thin-section ct| resolution computed-tomography| pulmonary-function tests| diffuse aspiration bronchiolitis| expiratory ct| spiral ct| tracheobronchial tree| lung transplantation| virtual bronchoscopy| helical ct	Grenier, PA; Beigelman-Aubry, C; Fetita, C; Preteux, F; Brauner, MW; Lenoir, S	New frontiers in CT imaging of airway disease		EUROPEAN RADIOLOGY	chronic obstructive pulmonary disease; airways; helical CT; 3D images	THIN-SECTION CT; RESOLUTION COMPUTED-TOMOGRAPHY; PULMONARY-FUNCTION TESTS; DIFFUSE ASPIRATION BRONCHIOLITIS; EXPIRATORY CT; SPIRAL CT; TRACHEOBRONCHIAL TREE; LUNG TRANSPLANTATION; VIRTUAL BRONCHOSCOPY; HELICAL CT	Combining helical volumetric CT acquisition and thin-slice thickness during breath hold provides an accurate assessment of both focal and diffuse airway diseases. With multiple detector rows, compared with single-slice helical CT, multislice CT can cover a greater volume, during a simple breath hold, and with better longitudinal and in-plane spatial resolution and improved temporal resolution. The result in data set allows the generation of superior multiplanar and 3D images of the airways, including those obtained from techniques developed specifically for airway imaging, such as virtual bronchography and virtual bronchoscopy. Complementary CT evaluation at suspended or continuous full expiration is mandatory to detect air trapping that is a key finding for depicting an obstruction on the small airways. Indications for CT evaluation of the airways include: (a) detection of endobronchial lesions in patients with an unexplained hemoptysis; (b) evaluation of extent of tracheobronchial stenosis for planning treatment and follow-up; (c) detection of congenital airway anomalies revealed by hemoptysis or recurrent infection; (d) detection of postinfectious or postoperative airway fistula or dehiscence, and (e) diagnosis and assessment of extent of bronchiectasis and small airway disease. Improvement in image analysis technique and the use of spirometrically control Of lung Volume acquisition have made possible accurate and reproducible quantitative assessment of airway wall and lumen areas and lung density. This contributes to better insights in physiopathology of obstructive lung disease, particularly in chronic obstructive pulmonary disease and asthma.	106	89	2002	23	10.1007/s00330-002-1342-1	Radiology, Nuclear Medicine & Medical Imaging
The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren. Background: Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. Methods: In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. Results: In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. Conclusions: Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population. Copyright (C) 2001 S. Karger AG, Basel.. atopy| skin test reactivity| malaria| helminth| schistosomiasis| filariasis| ige| africa|human lymphatic filariasis| schistosoma-haematobium| allergic reactivity| interferon-gamma| atopy| ige| infection| malaria| asthma| children.	NOV-2001	atopy| skin test reactivity| malaria| helminth| schistosomiasis| filariasis| ige| africa|human lymphatic filariasis| schistosoma-haematobium| allergic reactivity| interferon-gamma| atopy| ige| infection| malaria| asthma| children	van den Biggelaar, AHJ; Lopuhaa, C; van Ree, R; van der Zee, JS; Jans, J; Hoek, A; Migombet, B; Borrmann, S; Luckner, D; Kremsner, PG; Yazdanbakhsh, M	The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren		INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY	atopy; skin test reactivity; malaria; helminth; schistosomiasis; filariasis; IgE; Africa	HUMAN LYMPHATIC FILARIASIS; SCHISTOSOMA-HAEMATOBIUM; ALLERGIC REACTIVITY; INTERFERON-GAMMA; ATOPY; IGE; INFECTION; MALARIA; ASTHMA; CHILDREN	Background: Allergic diseases seem less prevalent in communities in less developed parts of the world, where parasite infections are highly prevalent. Altogether not much is known about the association between chronic infections with tissue and blood-dwelling parasites and atopy. Methods: In an area in Gabon endemic for blood and tissue parasites, 520 schoolchildren were parasitologically examined and skin prick-tested for a set of common environmental aeroallergens. Levels of allergen-specific IgE and polyclonal IgE were measured. Results: In schoolchildren schistosome and filarial infections increased with age, whereas malaria was more prevalent in younger children. In contrast to allergen sensitization that increased with age, skin test reactivity tended to decline. The number of children with mite-specific IgE antibodies (47%) by far exceeded the number responding to skin prick testing (11%). Mite sensitization was found to be the highest in children infected with schistosomes and/or filariae whereas skin test reactivity was lowest. The multiple logistic regression showed that the risk of a positive skin test was 8-fold higher with increasing levels of mite-specific IgE but was reduced by 72% when infected with blood stage helminths. Conclusions: Chronic blood and tissue parasite infections that are often capable of modulating immune responses in the host are negatively associated with skin test reactivity in a sensitized population. Copyright (C) 2001 S. Karger AG, Basel.	33	89	2001	8	10.1159/000049519	Allergy; Immunology
Cilomilast: a second generation phosphodiesterase 4 inhibitor for asthma and chronic obstructive pulmonary disease. Cilomilast (Ariflo(TM), SE-207499) is an orally-active, second generation phosphodiesterase (PDE) inhibitor that may be effective in the treatment of asthma and chronic obstructive pulmonary disease (COPD). It has high selectivity for the cyclic AMP-specific, or PDE4, isoenzyme that predominates in pro-inflammatory and immune cells and is ten-fold more selective for PDE4D than for PDE4A, B and C. In vitro, cilomilast suppresses the activity of many pro-inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD and is highly active in animal models of these diseases. Cilomilast demonstrates a markedly improved side effect profile over the archetypal PDE4 inhibitor, rolipram, which has been attributed to its inability to discriminate between the high affinity rolipram binding site and the catalytic domain of the enzyme, and the fact that it is negatively charged which at physiological pH should limit its penetration in to the CNS. In humans cilomilast is rapidly absorbed after oral administration, providing dose-proportional systemic exposure up to 4 mg, completely bioavailable, has a half-life of similar to 7 h and is subject to negligible first pass hepatic metabolism. Cilomilast is extensively metabolised with decyclopentylation, acyl glucuronidation and 3-hydroxylation of the cyclopentyl ring representing the principal routes. Most of the drug is excreted in the urine (similar to 90%) and faeces (6-7%) with unchanged cilomilast accounting for less than 1% of the administered dose. Cilomilast has been evaluated in Phase I, Phase II and Phase III trials and dose-response experiments have demonstrated a clinically significant increase in lung function and a perceived improvement in quality of life in patients with COPD. Trials of cilomilast in asthma have been less impressive although a trend towards improved lung function has been reported. Cilomilast is safe and well-tolerated at doses up to 15 mg in both short- and long-term dosing trials with a low incidence of adverse effects. No evidence for drug-drug interactions with commonly prescribed medications for COPD and asthma such as digoxin, corticosteroids, salbutamol, theophylline or warfarin has been found. Moreover, the pharmacokinetics of cilomilast are essentially the same in smokers and non-smokers, indicating that no dose adjustments of cilomilast will be required in patients with COPD. Thus, cilomilast displays a promising clinical profile in the treatment of inflammatory airway diseases, in particular COPD and the results of further Phase III trials are awaited with interest.. airways inflammation| asthma| ariflo| cilomilast| chronic obstructive pulmonary disease| cyclic amp| phosphodiesterase 4| sb-207439|human-liver-microsomes| affinity rolipram binding| selective pde4 inhibitor| theophylline metabolism| ariflo(tm) sb-207499| inhaled corticosteroids| catalytic activity| cigarette-smoking| se-207499 ariflo| human monocytes.	JUL-2001	airways inflammation| asthma| ariflo| cilomilast| chronic obstructive pulmonary disease| cyclic amp| phosphodiesterase 4| sb-207439|human-liver-microsomes| affinity rolipram binding| selective pde4 inhibitor| theophylline metabolism| ariflo(tm) sb-207499| inhaled corticosteroids| catalytic activity| cigarette-smoking| se-207499 ariflo| human monocytes	Giembycz, MA	Cilomilast: a second generation phosphodiesterase 4 inhibitor for asthma and chronic obstructive pulmonary disease		EXPERT OPINION ON INVESTIGATIONAL DRUGS	airways inflammation; asthma; Ariflo; cilomilast; chronic obstructive pulmonary disease; cyclic AMP; phosphodiesterase 4; SB-207439	HUMAN-LIVER-MICROSOMES; AFFINITY ROLIPRAM BINDING; SELECTIVE PDE4 INHIBITOR; THEOPHYLLINE METABOLISM; ARIFLO(TM) SB-207499; INHALED CORTICOSTEROIDS; CATALYTIC ACTIVITY; CIGARETTE-SMOKING; SE-207499 ARIFLO; HUMAN MONOCYTES	Cilomilast (Ariflo(TM), SE-207499) is an orally-active, second generation phosphodiesterase (PDE) inhibitor that may be effective in the treatment of asthma and chronic obstructive pulmonary disease (COPD). It has high selectivity for the cyclic AMP-specific, or PDE4, isoenzyme that predominates in pro-inflammatory and immune cells and is ten-fold more selective for PDE4D than for PDE4A, B and C. In vitro, cilomilast suppresses the activity of many pro-inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD and is highly active in animal models of these diseases. Cilomilast demonstrates a markedly improved side effect profile over the archetypal PDE4 inhibitor, rolipram, which has been attributed to its inability to discriminate between the high affinity rolipram binding site and the catalytic domain of the enzyme, and the fact that it is negatively charged which at physiological pH should limit its penetration in to the CNS. In humans cilomilast is rapidly absorbed after oral administration, providing dose-proportional systemic exposure up to 4 mg, completely bioavailable, has a half-life of similar to 7 h and is subject to negligible first pass hepatic metabolism. Cilomilast is extensively metabolised with decyclopentylation, acyl glucuronidation and 3-hydroxylation of the cyclopentyl ring representing the principal routes. Most of the drug is excreted in the urine (similar to 90%) and faeces (6-7%) with unchanged cilomilast accounting for less than 1% of the administered dose. Cilomilast has been evaluated in Phase I, Phase II and Phase III trials and dose-response experiments have demonstrated a clinically significant increase in lung function and a perceived improvement in quality of life in patients with COPD. Trials of cilomilast in asthma have been less impressive although a trend towards improved lung function has been reported. Cilomilast is safe and well-tolerated at doses up to 15 mg in both short- and long-term dosing trials with a low incidence of adverse effects. No evidence for drug-drug interactions with commonly prescribed medications for COPD and asthma such as digoxin, corticosteroids, salbutamol, theophylline or warfarin has been found. Moreover, the pharmacokinetics of cilomilast are essentially the same in smokers and non-smokers, indicating that no dose adjustments of cilomilast will be required in patients with COPD. Thus, cilomilast displays a promising clinical profile in the treatment of inflammatory airway diseases, in particular COPD and the results of further Phase III trials are awaited with interest.	125	89	2001	19	10.1517/13543784.10.7.1361	Pharmacology & Pharmacy
Skin sensitization testing in potency and risk assessment. The purpose of this article is to review, and make recommendations for, the use of relevant skin sensitization test methods, for the purposes of determination of relative potency and the threshold dose necessary for the induction of skin sensitization, and for risk assessment, In addressing the first area, the utility of three guinea pig tests (the guinea pig maximization test, the occluded patch test, and the open epicutaneous test) of the local lymph node assay (LLNA) and of human volunteer testing for the assessment of relative potency and identification of thresholds for sensitization were considered. The following conclusions were drawn. (1) Although attempts have been made to modify the guinea pig maximization test for the purposes of deriving dose-response relationships, this method is usually unsuitable for determination of relative sensitizing potency. (2) Guinea pig methods that do not require the use of adjuvant and which employ a relevant route of exposure (the occluded patch test and the open epicutaneous test) are more appropriate for the assessment of relative skin-sensitizing potency. (3) The LLNA is suitable for the determination of relative skin sensitizing potency, and the adaptation of this method for derivation of comparative criteria such as EC3 values (the estimated concentration of test chemical required to induce a stimulation index of 3 in the LLNA) provides an effective and quantitative basis for such measurements, (4) For all the methods identified above, potency is assessed relative to other chemical allergens of known skin sensitizing potential. The estimation of likely threshold concentrations is dependent upon the availability of suitable benchmark chemicals of known potency for human sensitization. (5) Human testing (and specifically, the Human Repeat Insult Patch Test) can provide information of value in confirming the absence of skin sensitizing activity of formulations and products under specific conditions of use and exposure. Based on the above, the following recommendations are made. (1) If results are already available from suitable guinea pig tests, then judicious interpretation of the data may provide information of value in assessing relative skin sensitizing potency. This option should be explored before other analyses are conducted. (2) The LLNA is the recommended method for new assessments of relative potency, and/or for the investigation of the influence of vehicle or formulation on skin sensitizing potency. (3) Whenever available, human skin sensitization data should be incorporated into an assessment of relative potency. With respect to risk assessment, the conclusion drawn is that all the available data on skin-sensitizing activity in animals and man should be integrated into the risk-assessment process. Appropriate interpretation of existing data from suitable guinea pig studies can provide valuable information with respect to potency, as the first step in the development of a risk assessment. However, for de novo investigations, the LLNA is the method favored for providing quantitative estimations of skin-sensitizing potency that are best suited to the risk assessment process. Finally, human testing is of value in the risk assessment process, but is performed only for the purposes of confirming product safety.. skin sensitization| sensitization potency| risk assessment| guinea pig tests| local lymph node assay| human sensitization|lymph-node assay| pig maximization test| allergic contact sensitization| false-positive responses| predictive test methods| guinea-pig| cell| products| agents| sensitivity.	FEB-2001	skin sensitization| sensitization potency| risk assessment| guinea pig tests| local lymph node assay| human sensitization|lymph-node assay| pig maximization test| allergic contact sensitization| false-positive responses| predictive test methods| guinea-pig| cell| products| agents| sensitivity	Kimber, I; Basketter, DA; Berthold, K; Butler, M; Garrigue, JL; Lea, L; Newsome, C; Roggeband, R; Steiling, W; Stropp, G; Waterman, S; Wiemann, C	Skin sensitization testing in potency and risk assessment		TOXICOLOGICAL SCIENCES	skin sensitization; sensitization potency; risk assessment; guinea pig tests; local lymph node assay; human sensitization	LYMPH-NODE ASSAY; PIG MAXIMIZATION TEST; ALLERGIC CONTACT SENSITIZATION; FALSE-POSITIVE RESPONSES; PREDICTIVE TEST METHODS; GUINEA-PIG; CELL; PRODUCTS; AGENTS; SENSITIVITY	The purpose of this article is to review, and make recommendations for, the use of relevant skin sensitization test methods, for the purposes of determination of relative potency and the threshold dose necessary for the induction of skin sensitization, and for risk assessment, In addressing the first area, the utility of three guinea pig tests (the guinea pig maximization test, the occluded patch test, and the open epicutaneous test) of the local lymph node assay (LLNA) and of human volunteer testing for the assessment of relative potency and identification of thresholds for sensitization were considered. The following conclusions were drawn. (1) Although attempts have been made to modify the guinea pig maximization test for the purposes of deriving dose-response relationships, this method is usually unsuitable for determination of relative sensitizing potency. (2) Guinea pig methods that do not require the use of adjuvant and which employ a relevant route of exposure (the occluded patch test and the open epicutaneous test) are more appropriate for the assessment of relative skin-sensitizing potency. (3) The LLNA is suitable for the determination of relative skin sensitizing potency, and the adaptation of this method for derivation of comparative criteria such as EC3 values (the estimated concentration of test chemical required to induce a stimulation index of 3 in the LLNA) provides an effective and quantitative basis for such measurements, (4) For all the methods identified above, potency is assessed relative to other chemical allergens of known skin sensitizing potential. The estimation of likely threshold concentrations is dependent upon the availability of suitable benchmark chemicals of known potency for human sensitization. (5) Human testing (and specifically, the Human Repeat Insult Patch Test) can provide information of value in confirming the absence of skin sensitizing activity of formulations and products under specific conditions of use and exposure. Based on the above, the following recommendations are made. (1) If results are already available from suitable guinea pig tests, then judicious interpretation of the data may provide information of value in assessing relative skin sensitizing potency. This option should be explored before other analyses are conducted. (2) The LLNA is the recommended method for new assessments of relative potency, and/or for the investigation of the influence of vehicle or formulation on skin sensitizing potency. (3) Whenever available, human skin sensitization data should be incorporated into an assessment of relative potency. With respect to risk assessment, the conclusion drawn is that all the available data on skin-sensitizing activity in animals and man should be integrated into the risk-assessment process. Appropriate interpretation of existing data from suitable guinea pig studies can provide valuable information with respect to potency, as the first step in the development of a risk assessment. However, for de novo investigations, the LLNA is the method favored for providing quantitative estimations of skin-sensitizing potency that are best suited to the risk assessment process. Finally, human testing is of value in the risk assessment process, but is performed only for the purposes of confirming product safety.	76	89	2001	11	10.1093/toxsci/59.2.198	Toxicology
Association of asthma symptoms and severity with indoor bioaerosols. Background: In this study, repeated measurements were made of levels of mold spores, bacteria, and dust-mite allergens over a 7-month period in the homes of asthmatics, and relationships with measures of asthma severity were evaluated. Methods: A sample of 57 asthmatic individuals, living in 44 homes in East Moline, Illinois, and nearby communities, participated in a panel study. The homes were visited up to nine times during the study to collect air and dust samples. Asthma severity indicators were derived from questionnaire data and from the daily health records from the panel study. Associations between indoor levels of mold spores, bacteria, and dust-mite allergens were tested with several asthma severity indicators. Results: There was evidence of associations between all asthma severity measures and levels of total and Gram-negative bacteria, but mold-spore abundance was associated only with emergency room (ER) visits for asthma. No significant associations were found with house-dust-mite allergen and any of the asthma severity indicators, but the levels of dust-mite allergen were low, with median concentrations of 0.18 mu g/g dust Der f 1 and 0.19 mu g/g dust Der p 1. Conclusions: Some evidence was found for associations of increased concentrations of Gram-negative bacteria and mold spores with asthma severity, particularly with ER visits. No association was found between house-dust-mite allergen and asthma severity indicators; however, the mite-allergen levels in the study homes were generally well below the proposed threshold level of 2 mu g/g dust.. allergens| asthma| bacteria| dampness| dust mites| flooding| mold spores|dust-mite-allergen| endotoxin exposure| respiratory health| control children| risk factor| house| home| childhood| fungi.	AUG-2000	allergens| asthma| bacteria| dampness| dust mites| flooding| mold spores|dust-mite-allergen| endotoxin exposure| respiratory health| control children| risk factor| house| home| childhood| fungi	Ross, MA; Curtis, L; Scheff, PA; Hryhorczuk, DO; Ramakrishnan, V; Wadden, RA; Persky, VW	Association of asthma symptoms and severity with indoor bioaerosols		ALLERGY	allergens; asthma; bacteria; dampness; dust mites; flooding; mold spores	DUST-MITE-ALLERGEN; ENDOTOXIN EXPOSURE; RESPIRATORY HEALTH; CONTROL CHILDREN; RISK FACTOR; HOUSE; HOME; CHILDHOOD; FUNGI	Background: In this study, repeated measurements were made of levels of mold spores, bacteria, and dust-mite allergens over a 7-month period in the homes of asthmatics, and relationships with measures of asthma severity were evaluated. Methods: A sample of 57 asthmatic individuals, living in 44 homes in East Moline, Illinois, and nearby communities, participated in a panel study. The homes were visited up to nine times during the study to collect air and dust samples. Asthma severity indicators were derived from questionnaire data and from the daily health records from the panel study. Associations between indoor levels of mold spores, bacteria, and dust-mite allergens were tested with several asthma severity indicators. Results: There was evidence of associations between all asthma severity measures and levels of total and Gram-negative bacteria, but mold-spore abundance was associated only with emergency room (ER) visits for asthma. No significant associations were found with house-dust-mite allergen and any of the asthma severity indicators, but the levels of dust-mite allergen were low, with median concentrations of 0.18 mu g/g dust Der f 1 and 0.19 mu g/g dust Der p 1. Conclusions: Some evidence was found for associations of increased concentrations of Gram-negative bacteria and mold spores with asthma severity, particularly with ER visits. No association was found between house-dust-mite allergen and asthma severity indicators; however, the mite-allergen levels in the study homes were generally well below the proposed threshold level of 2 mu g/g dust.	23	89	2000	7	10.1034/j.1398-9995.2000.00551.x	Allergy; Immunology
Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. Background: Glucocorticoids are used as mainstay therapy for asthma, but some patients remain resistant to therapy. MicroRNAs (miRNAs) are important regulators of the immune system by promoting the catabolism of their target transcripts as well as attenuating their translation. The role of miRNA in regulating allergic inflammation remains largely unknown. Blocking miRNA function may provide a new nonsteroidal anti-inflammatory approach to treatment. Objectives: To (1) determine the role of specific miRNAs in the regulation of hallmark features of allergic airways inflammation and (2) compare the efficacy of antagonizing miRNA function with that of steroid treatment. Methods: Mice were sensitized and then aeroallergen-challenged with house dust mite to induce allergic airways disease, and alterations in the expression of miRNAs were characterized. Next mice were treated with antagomirs that inhibited the function of specific miRNAs in the lung or treated with dexamethasone and inflammatory lesions, and airway hyperresponsiveness was measured. Results: miR-145, miR-21, and let-7b have been implicated in airway smooth muscle function, inflammation, and airways epithelial cell function, respectively. Inhibition of miR-145, but not miR-21 or lethal-7b, inhibited eosinophilic inflammation, mucus hypersecretion, T(H)2 cytokine production, and airway hyperresponsiveness. The anti-inflammatory effects of miR-145 antagonism were comparable to steroid treatment. Conclusion: Our study highlights the importance of understanding the contribution of miRNAs to pathogenesis of human allergic disease and their potential as novel anti-inflammatory targets. (J Allergy Clin Immunol 2011; 128: 160-7.). mirna| asthma| allergy| inflammation| dexamethasone| glucocorticoid| hdm| antagomir|experimental asthma| eosinophil recruitment| immune-system| t(h)2 cells| in-vivo| expression| modulation| inflammation| mechanisms| model.	JUL-2011	mirna| asthma| allergy| inflammation| dexamethasone| glucocorticoid| hdm| antagomir|experimental asthma| eosinophil recruitment| immune-system| t(h)2 cells| in-vivo| expression| modulation| inflammation| mechanisms| model	Collison, A; Mattes, J; Plank, M; Foster, PS	Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	miRNA; asthma; allergy; inflammation; dexamethasone; glucocorticoid; HDM; antagomir	EXPERIMENTAL ASTHMA; EOSINOPHIL RECRUITMENT; IMMUNE-SYSTEM; T(H)2 CELLS; IN-VIVO; EXPRESSION; MODULATION; INFLAMMATION; MECHANISMS; MODEL	Background: Glucocorticoids are used as mainstay therapy for asthma, but some patients remain resistant to therapy. MicroRNAs (miRNAs) are important regulators of the immune system by promoting the catabolism of their target transcripts as well as attenuating their translation. The role of miRNA in regulating allergic inflammation remains largely unknown. Blocking miRNA function may provide a new nonsteroidal anti-inflammatory approach to treatment. Objectives: To (1) determine the role of specific miRNAs in the regulation of hallmark features of allergic airways inflammation and (2) compare the efficacy of antagonizing miRNA function with that of steroid treatment. Methods: Mice were sensitized and then aeroallergen-challenged with house dust mite to induce allergic airways disease, and alterations in the expression of miRNAs were characterized. Next mice were treated with antagomirs that inhibited the function of specific miRNAs in the lung or treated with dexamethasone and inflammatory lesions, and airway hyperresponsiveness was measured. Results: miR-145, miR-21, and let-7b have been implicated in airway smooth muscle function, inflammation, and airways epithelial cell function, respectively. Inhibition of miR-145, but not miR-21 or lethal-7b, inhibited eosinophilic inflammation, mucus hypersecretion, T(H)2 cytokine production, and airway hyperresponsiveness. The anti-inflammatory effects of miR-145 antagonism were comparable to steroid treatment. Conclusion: Our study highlights the importance of understanding the contribution of miRNAs to pathogenesis of human allergic disease and their potential as novel anti-inflammatory targets. (J Allergy Clin Immunol 2011; 128: 160-7.)	45	88	2011	12	10.1016/j.jaci.2011.04.005	Allergy; Immunology
Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes. The innate signaling pathways for Th2 immunity activated by inhaled antigens are not well defined. We previously identified Dectin-2 as a receptor for glycans in allergen extracts from the house dust mite Dermatophagoides farinae (Df) that mediates cysteinyl leukotriene (cys-LT) generation from pulmonary CD11c(+) cells and from GM-CSF-cultured bone marrow cells (BMCsGM-CSF) Using lentiviral knockdown of Dectin-2 in BMCsGM-CSF and adoptive transfer of Df-pulsed BMCsGm-csF to sensitize naive mice, we now report that Dectin-2 is critical for the development of Df-elicited eosinophilic and neutrophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. Sensitization with Df-pulsed BMCsGM-CSF from LTC4 synthase(LTC,S)-deficient mice or type 1 cys-LT receptor (CysLT,R)-deficient mice demonstrated that both proteins were required for Df-elicited eosinophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. Direct sensitization and challenge of Ltc4s(-/-) and Cysitr1(-/-) mice confirmed that cys-LTs mediate these parameters of Df-elicited Th2 pulmonary inflammation. Thus, the Dectin-2-cys-LT pathway is critical for the induction of Th2 immunity to a major allergen, in part through CysLT(1)R. These findings identify a previously unrecognized link between a myeloid C-type lectin receptor and Th2 immunity.. human polymorphonuclear leukocytes| pattern-recognition receptor| mansoni egg antigens| dust mite allergen| dendritic cells| inhaled antigen| vascular-permeability| airway inflammation| schistosoma-mansoni| mice lacking.	MAR 14-2011	human polymorphonuclear leukocytes| pattern-recognition receptor| mansoni egg antigens| dust mite allergen| dendritic cells| inhaled antigen| vascular-permeability| airway inflammation| schistosoma-mansoni| mice lacking	Barrett, NA; Rahman, OM; Fernandez, JM; Parsons, MW; Xing, W; Austen, KF; Kanaoka, Y	Dectin-2 mediates Th2 immunity through the generation of cysteinyl leukotrienes		JOURNAL OF EXPERIMENTAL MEDICINE		HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PATTERN-RECOGNITION RECEPTOR; MANSONI EGG ANTIGENS; DUST MITE ALLERGEN; DENDRITIC CELLS; INHALED ANTIGEN; VASCULAR-PERMEABILITY; AIRWAY INFLAMMATION; SCHISTOSOMA-MANSONI; MICE LACKING	The innate signaling pathways for Th2 immunity activated by inhaled antigens are not well defined. We previously identified Dectin-2 as a receptor for glycans in allergen extracts from the house dust mite Dermatophagoides farinae (Df) that mediates cysteinyl leukotriene (cys-LT) generation from pulmonary CD11c(+) cells and from GM-CSF-cultured bone marrow cells (BMCsGM-CSF) Using lentiviral knockdown of Dectin-2 in BMCsGM-CSF and adoptive transfer of Df-pulsed BMCsGm-csF to sensitize naive mice, we now report that Dectin-2 is critical for the development of Df-elicited eosinophilic and neutrophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. Sensitization with Df-pulsed BMCsGM-CSF from LTC4 synthase(LTC,S)-deficient mice or type 1 cys-LT receptor (CysLT,R)-deficient mice demonstrated that both proteins were required for Df-elicited eosinophilic pulmonary inflammation and Th2 cytokine generation in the lungs and restimulated lymph nodes. Direct sensitization and challenge of Ltc4s(-/-) and Cysitr1(-/-) mice confirmed that cys-LTs mediate these parameters of Df-elicited Th2 pulmonary inflammation. Thus, the Dectin-2-cys-LT pathway is critical for the induction of Th2 immunity to a major allergen, in part through CysLT(1)R. These findings identify a previously unrecognized link between a myeloid C-type lectin receptor and Th2 immunity.	42	88	2011	12	10.1084/jem.20100793	Immunology; Research & Experimental Medicine
Chronic Obstructive Pulmonary Disease and Long-Term Exposure to Traffic-related Air Pollution A Cohort Study. Rationale: Short-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood. Objectives: We assessed the effect of exposure to traffic-related air pollution over 35 years on the incidence of COPD in a prospective cohort study. Methods: We followed 57,053 participants in the Danish Diet, Cancer, and Health cohort in the Hospital Discharge Register for their first hospital admission for COPD between 1993 and 2006. We estimated the annual mean levels of nitrogen dioxide (NO(2)) and nitrogen oxides (NO(x)) at all residential addresses of the cohort participants since 1971 to an event or 2006 and used indicators of traffic near the residential address at recruitment. We assessed the association between exposure to air pollution and COPD incidence by Cox regression analyses for the full cohort, and for participants with and without comorbid conditions, including asthma, diabetes, or cardiovascular disease. Measurements and Main Results: A first hospital admission for COPD was recorded for 1,786 (3.4%) of 52,799 eligible subjects between recruitment (1993-1997) and 2006. COPD incidence was associated with the 35-year mean NO(2) level (hazard ratio, 1.08; 95% confidence interval, 1.02-1.14, per interquartile range of 5.8 mu g/m(3)), with stronger associations in subjects with diabetes (1.29; 1.05-1.50) and asthma (1.19; 1.03-1.38). Conclusions: Long-term exposure to traffic-related air pollution may contribute to the development of COPD with possibly enhanced susceptibility in people with diabetes and asthma.. copd| air pollution| hospital admission| asthma| diabetes|lung-function| respiratory symptoms| nitrogen-dioxide| health| risk| copd| cancer| atherosclerosis| inflammation| population.	FEB 15-2011	copd| air pollution| hospital admission| asthma| diabetes|lung-function| respiratory symptoms| nitrogen-dioxide| health| risk| copd| cancer| atherosclerosis| inflammation| population	Andersen, ZJ; Hvidberg, M; Jensen, SS; Ketzel, M; Loft, S; Sorensen, M; Tjonneland, A; Overvad, K; Raaschou-Nielsen, O	Chronic Obstructive Pulmonary Disease and Long-Term Exposure to Traffic-related Air Pollution A Cohort Study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	COPD; air pollution; hospital admission; asthma; diabetes	LUNG-FUNCTION; RESPIRATORY SYMPTOMS; NITROGEN-DIOXIDE; HEALTH; RISK; COPD; CANCER; ATHEROSCLEROSIS; INFLAMMATION; POPULATION	Rationale: Short-term exposure to air pollution has been associated with exacerbation of chronic obstructive pulmonary disease (COPD), whereas the role of long-term exposures on the development of COPD is not yet fully understood. Objectives: We assessed the effect of exposure to traffic-related air pollution over 35 years on the incidence of COPD in a prospective cohort study. Methods: We followed 57,053 participants in the Danish Diet, Cancer, and Health cohort in the Hospital Discharge Register for their first hospital admission for COPD between 1993 and 2006. We estimated the annual mean levels of nitrogen dioxide (NO(2)) and nitrogen oxides (NO(x)) at all residential addresses of the cohort participants since 1971 to an event or 2006 and used indicators of traffic near the residential address at recruitment. We assessed the association between exposure to air pollution and COPD incidence by Cox regression analyses for the full cohort, and for participants with and without comorbid conditions, including asthma, diabetes, or cardiovascular disease. Measurements and Main Results: A first hospital admission for COPD was recorded for 1,786 (3.4%) of 52,799 eligible subjects between recruitment (1993-1997) and 2006. COPD incidence was associated with the 35-year mean NO(2) level (hazard ratio, 1.08; 95% confidence interval, 1.02-1.14, per interquartile range of 5.8 mu g/m(3)), with stronger associations in subjects with diabetes (1.29; 1.05-1.50) and asthma (1.19; 1.03-1.38). Conclusions: Long-term exposure to traffic-related air pollution may contribute to the development of COPD with possibly enhanced susceptibility in people with diabetes and asthma.	35	88	2011	7	10.1164/rccm.201006-0937OC	General & Internal Medicine; Respiratory System
"The human health effects of ozone depletion and interactions with climate change. Depletion of the stratospheric ozone layer has led to increased solar UV-B radiation (280-315 nm) at the surface of the Earth. This change is likely to have had an impact on human exposure to UV-B radiation with consequential detrimental and beneficial effects on health, although behavioural changes in society over the past 60 years or so with regard to sun exposure are of considerable importance. The present report concentrates on information published since our previous report in 2007. The adverse effects of UV radiation are primarily on the eye and the skin. While solar UV radiation is a recognised risk factor for some types of cataract and for pterygium, the evidence is less strong, although increasing, for ocular melanoma, and is equivocal at present for age-related macular degeneration. For the skin, the most common harmful outcome is skin cancer, including melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma. The incidence of all three of these tumours has risen significantly over the past five decades, particularly in people with fair skin, and is projected to continue to increase, thus posing a significant world-wide health burden. Overexposure to the sun is the major identified environmental risk factor in skin cancer, in association with various genetic risk factors and immune effects. Suppression of some aspects of immunity follows exposure to UV radiation and the consequences of this modulation for the immune control of infectious diseases, for vaccination and for tumours, are additional concerns. In a common sun allergy (polymorphic light eruption), there is an imbalance in the immune response to UV radiation, resulting in a sun-evoked rash. The major health benefit of exposure to solar UV-B radiation is the production of vitamin D. Vitamin D plays a crucial role in bone metabolism and is also implicated in protection against a wide range of diseases. Although there is some evidence supporting protective effects for a range of internal cancers, this is not yet conclusive, but strongest for colorectal cancer, at present. A role for vitamin D in protection against several autoimmune diseases has been studied, with the most convincing results to date for multiple sclerosis. Vitamin D is starting to be assessed for its protective properties against several infectious and coronary diseases. Current methods for protecting the eye and the skin from the adverse effects of solar UV radiation are evaluated, including seeking shade, wearing protective clothing and sunglasses, and using sunscreens. Newer possibilities are considered such as creams that repair UV-induced DNA damage, and substances applied topically to the skin or eaten in the diet that protect against some of the detrimental effects of sun exposure. It is difficult to provide easily understandable public health messages regarding ""safe"" sun exposure, so that the positive effects of vitamin D production are balanced against the negative effects of excessive exposure. The international response to ozone depletion has included the development and deployment of replacement technologies and chemicals. To date, limited evidence suggests that substitutes for the ozone-depleting substances do not have significant effects on human health. In addition to stratospheric ozone depletion, climate change is predicted to affect human health, and potential interactions between these two parameters are considered. These include altering the risk of developing skin tumours, infectious diseases and various skin diseases, in addition to altering th efficiency by which pathogenic microorganisms are inactivated in the environment.. nonmelanoma skin-cancer| basal-cell carcinoma| vitamin-d status| type-1 diabetes-mellitus| cutaneous malignant-melanoma| polymorphic light eruption| hepatitis-b vaccination| regulatory-t-cells| circulating 25-hydroxyvitamin-d levels| radiation-induced immunosuppression."	2011	nonmelanoma skin-cancer| basal-cell carcinoma| vitamin-d status| type-1 diabetes-mellitus| cutaneous malignant-melanoma| polymorphic light eruption| hepatitis-b vaccination| regulatory-t-cells| circulating 25-hydroxyvitamin-d levels| radiation-induced immunosuppression	Norval, M; Lucas, RM; Cullen, AP; de Gruijl, FR; Longstreth, J; Takizawa, Y; van der Leun, JC	The human health effects of ozone depletion and interactions with climate change		PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES		NONMELANOMA SKIN-CANCER; BASAL-CELL CARCINOMA; VITAMIN-D STATUS; TYPE-1 DIABETES-MELLITUS; CUTANEOUS MALIGNANT-MELANOMA; POLYMORPHIC LIGHT ERUPTION; HEPATITIS-B VACCINATION; REGULATORY-T-CELLS; CIRCULATING 25-HYDROXYVITAMIN-D LEVELS; RADIATION-INDUCED IMMUNOSUPPRESSION	"Depletion of the stratospheric ozone layer has led to increased solar UV-B radiation (280-315 nm) at the surface of the Earth. This change is likely to have had an impact on human exposure to UV-B radiation with consequential detrimental and beneficial effects on health, although behavioural changes in society over the past 60 years or so with regard to sun exposure are of considerable importance. The present report concentrates on information published since our previous report in 2007. The adverse effects of UV radiation are primarily on the eye and the skin. While solar UV radiation is a recognised risk factor for some types of cataract and for pterygium, the evidence is less strong, although increasing, for ocular melanoma, and is equivocal at present for age-related macular degeneration. For the skin, the most common harmful outcome is skin cancer, including melanoma and the non-melanoma skin cancers, basal cell carcinoma and squamous cell carcinoma. The incidence of all three of these tumours has risen significantly over the past five decades, particularly in people with fair skin, and is projected to continue to increase, thus posing a significant world-wide health burden. Overexposure to the sun is the major identified environmental risk factor in skin cancer, in association with various genetic risk factors and immune effects. Suppression of some aspects of immunity follows exposure to UV radiation and the consequences of this modulation for the immune control of infectious diseases, for vaccination and for tumours, are additional concerns. In a common sun allergy (polymorphic light eruption), there is an imbalance in the immune response to UV radiation, resulting in a sun-evoked rash. The major health benefit of exposure to solar UV-B radiation is the production of vitamin D. Vitamin D plays a crucial role in bone metabolism and is also implicated in protection against a wide range of diseases. Although there is some evidence supporting protective effects for a range of internal cancers, this is not yet conclusive, but strongest for colorectal cancer, at present. A role for vitamin D in protection against several autoimmune diseases has been studied, with the most convincing results to date for multiple sclerosis. Vitamin D is starting to be assessed for its protective properties against several infectious and coronary diseases. Current methods for protecting the eye and the skin from the adverse effects of solar UV radiation are evaluated, including seeking shade, wearing protective clothing and sunglasses, and using sunscreens. Newer possibilities are considered such as creams that repair UV-induced DNA damage, and substances applied topically to the skin or eaten in the diet that protect against some of the detrimental effects of sun exposure. It is difficult to provide easily understandable public health messages regarding ""safe"" sun exposure, so that the positive effects of vitamin D production are balanced against the negative effects of excessive exposure. The international response to ozone depletion has included the development and deployment of replacement technologies and chemicals. To date, limited evidence suggests that substitutes for the ozone-depleting substances do not have significant effects on human health. In addition to stratospheric ozone depletion, climate change is predicted to affect human health, and potential interactions between these two parameters are considered. These include altering the risk of developing skin tumours, infectious diseases and various skin diseases, in addition to altering th efficiency by which pathogenic microorganisms are inactivated in the environment."	376	88	2011	27	10.1039/c0pp90044c	Biochemistry & Molecular Biology; Biophysics; Chemistry
Long-term exposure to close-proximity air pollution and asthma and allergies in urban children. The aim of this study was to evaluate the impact of urban air pollution, assessed through reliable indicators of exposure, on asthma and allergies in schoolchildren. A validated dispersion model combining data on traffic conditions, topography, meteorology and background pollution was used to relate 3-yrs averaged concentrations of major urban pollutants at the sites of schools to skin prick tests, exercise-induced asthma and reported asthma and allergies in 6,683 children (9-11 yrs) attending 108 schools randomly selected in six French communities. For the 4,907 children who had resided at their current address for the past 3 yrs, asthma (exercise induced, past year and lifetime) was significantly positively associated with benzene, SO(2), particles with a 50% cut-off aerodynamic diameter of 10 mm (PM(10)), nitrogen oxides (NO(x)) and CO. In the same children, eczema (lifetime and past year) was significantly positively associated with benzene, PM(10), NO(2), NO x and CO, lifetime allergic rhinitis with PM(10) and sensitisation to pollens with benzene and PM(10). Among the 2,213 children residing at their current address since birth, the associations persisted for lifetime asthma with benzene (adjusted OR per interquartile range (95% CI) 1.3 (1.0-1.9)) and PM10 (1.4 (1.0-2.0)), and for sensitisation to pollens with volatile organic compounds (1.3 (1.0-1.9)) and PM10 (1.2 (1.0-1.9)). Accurately modelled urban air pollution was associated with some measures of childhood asthma and allergies.. air pollution| allergic rhinitis| allergic sensitisation| asthma| eczema| exposure assessment|respiratory health| childhood asthma| nitrogen-dioxide| diesel exhaust| particles| schoolchildren| symptoms| outdoor| cohort| isaac.	JUL-2010	air pollution| allergic rhinitis| allergic sensitisation| asthma| eczema| exposure assessment|respiratory health| childhood asthma| nitrogen-dioxide| diesel exhaust| particles| schoolchildren| symptoms| outdoor| cohort| isaac	Penard-Morand, C; Raherison, C; Charpin, D; Kopferschmitt, C; Lavaud, F; Caillaud, D; Annesi-Maesano, I	Long-term exposure to close-proximity air pollution and asthma and allergies in urban children		EUROPEAN RESPIRATORY JOURNAL	Air pollution; allergic rhinitis; allergic sensitisation; asthma; eczema; exposure assessment	RESPIRATORY HEALTH; CHILDHOOD ASTHMA; NITROGEN-DIOXIDE; DIESEL EXHAUST; PARTICLES; SCHOOLCHILDREN; SYMPTOMS; OUTDOOR; COHORT; ISAAC	The aim of this study was to evaluate the impact of urban air pollution, assessed through reliable indicators of exposure, on asthma and allergies in schoolchildren. A validated dispersion model combining data on traffic conditions, topography, meteorology and background pollution was used to relate 3-yrs averaged concentrations of major urban pollutants at the sites of schools to skin prick tests, exercise-induced asthma and reported asthma and allergies in 6,683 children (9-11 yrs) attending 108 schools randomly selected in six French communities. For the 4,907 children who had resided at their current address for the past 3 yrs, asthma (exercise induced, past year and lifetime) was significantly positively associated with benzene, SO(2), particles with a 50% cut-off aerodynamic diameter of 10 mm (PM(10)), nitrogen oxides (NO(x)) and CO. In the same children, eczema (lifetime and past year) was significantly positively associated with benzene, PM(10), NO(2), NO x and CO, lifetime allergic rhinitis with PM(10) and sensitisation to pollens with benzene and PM(10). Among the 2,213 children residing at their current address since birth, the associations persisted for lifetime asthma with benzene (adjusted OR per interquartile range (95% CI) 1.3 (1.0-1.9)) and PM10 (1.4 (1.0-2.0)), and for sensitisation to pollens with volatile organic compounds (1.3 (1.0-1.9)) and PM10 (1.2 (1.0-1.9)). Accurately modelled urban air pollution was associated with some measures of childhood asthma and allergies.	32	88	2010	8	10.1183/09031936.00116109	Respiratory System
Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial. B-type CpG oligodeoxynucleotides (ODN) is currently used in clinical trials because of its prolonged half-life, which is due to its phosphorothioate backbone. A-type CpG ODN is a stronger inducer of IFN but has an unstable phosphodiester backbone that has so far prohibited its clinical use. However, upon association with virus-like particles (VLP) consisting of the bacteriophage Q beta coat protein, A-type CpG ODN can be stabilized and can become an efficient adjuvant in mice. Therefore, the phase I/IIa study presented represents the first test of A-type CpGs in humans. To test the safety, tolerability and clinical efficacy of QbG10 as an adjuvant for subcutaneous immunotherapy with a house dust mite (HDM) allergen extract in allergic patients. A single centre, open-label phase I/IIa study evaluated the safety, tolerability and clinical efficacy of QbG10 as an adjuvant to immunotherapy with a subcutaneous HMD allergen extract in 20 patients suffering from HDM allergy. Twenty-one patients were enrolled between March and July 2005. Individual immunotherapy lasted 10 weeks. Clinical end-points included questionnaires, conjunctival provocation, skin prick tests and the measurement of allergen-specific IgG and IgE. QbG10 was well tolerated. Almost complete tolerance to the allergen was observed in conjunctival provocation testing after treatment with QbG10, and symptoms of rhinitis and allergic asthma were significantly reduced. Within 10 weeks of therapy, patients were nearly symptom-free and this amelioration lasted for at least 38 weeks post-treatment. Following injections of QbG10 and HDM allergen extract, allergen-specific IgG increased, while there was a transient increase in allergen-specific IgE titres. Skin reactivity to HDM was reduced. The subcutaneous application of HDM allergen, together with A-type CpG ODN packaged into VLP, was safe. All patients achieved practically complete alleviation of allergy symptoms after 10 weeks of immunotherapy. This promising clinical outcome calls for larger placebo-controlled phase II studies. G. Senti, P. Johansen, S. Haug, C. Bull, C. Gottschaller, P. Muller, T. Pfister, P. Maurer, M. F. Bachmann, N. Graf and T. M. Kundig, Clinical & Experimental Allergy, 2009 (39) 562-570.. allergy| house dust mite| specific immunotherapy| type a cpg| virus-like particles|house-dust-mite| monophosphoryl-lipid-a| dermatophagoides-pteronyssinus| bronchial hyperreactivity| immunostimulatory dna| pollen immunotherapy| asthmatic-children| dendritic cells| ragweed allergy| bacterial-dna.	APR-2009	allergy| house dust mite| specific immunotherapy| type a cpg| virus-like particles|house-dust-mite| monophosphoryl-lipid-a| dermatophagoides-pteronyssinus| bronchial hyperreactivity| immunostimulatory dna| pollen immunotherapy| asthmatic-children| dendritic cells| ragweed allergy| bacterial-dna	Senti, G; Johansen, P; Haug, S; Bull, C; Gottschaller, C; Muller, P; Pfister, T; Maurer, P; Bachmann, MF; Graf, N; Kundig, TM	Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; house dust mite; specific immunotherapy; Type A CpG; virus-like particles	HOUSE-DUST-MITE; MONOPHOSPHORYL-LIPID-A; DERMATOPHAGOIDES-PTERONYSSINUS; BRONCHIAL HYPERREACTIVITY; IMMUNOSTIMULATORY DNA; POLLEN IMMUNOTHERAPY; ASTHMATIC-CHILDREN; DENDRITIC CELLS; RAGWEED ALLERGY; BACTERIAL-DNA	B-type CpG oligodeoxynucleotides (ODN) is currently used in clinical trials because of its prolonged half-life, which is due to its phosphorothioate backbone. A-type CpG ODN is a stronger inducer of IFN but has an unstable phosphodiester backbone that has so far prohibited its clinical use. However, upon association with virus-like particles (VLP) consisting of the bacteriophage Q beta coat protein, A-type CpG ODN can be stabilized and can become an efficient adjuvant in mice. Therefore, the phase I/IIa study presented represents the first test of A-type CpGs in humans. To test the safety, tolerability and clinical efficacy of QbG10 as an adjuvant for subcutaneous immunotherapy with a house dust mite (HDM) allergen extract in allergic patients. A single centre, open-label phase I/IIa study evaluated the safety, tolerability and clinical efficacy of QbG10 as an adjuvant to immunotherapy with a subcutaneous HMD allergen extract in 20 patients suffering from HDM allergy. Twenty-one patients were enrolled between March and July 2005. Individual immunotherapy lasted 10 weeks. Clinical end-points included questionnaires, conjunctival provocation, skin prick tests and the measurement of allergen-specific IgG and IgE. QbG10 was well tolerated. Almost complete tolerance to the allergen was observed in conjunctival provocation testing after treatment with QbG10, and symptoms of rhinitis and allergic asthma were significantly reduced. Within 10 weeks of therapy, patients were nearly symptom-free and this amelioration lasted for at least 38 weeks post-treatment. Following injections of QbG10 and HDM allergen extract, allergen-specific IgG increased, while there was a transient increase in allergen-specific IgE titres. Skin reactivity to HDM was reduced. The subcutaneous application of HDM allergen, together with A-type CpG ODN packaged into VLP, was safe. All patients achieved practically complete alleviation of allergy symptoms after 10 weeks of immunotherapy. This promising clinical outcome calls for larger placebo-controlled phase II studies. G. Senti, P. Johansen, S. Haug, C. Bull, C. Gottschaller, P. Muller, T. Pfister, P. Maurer, M. F. Bachmann, N. Graf and T. M. Kundig, Clinical & Experimental Allergy, 2009 (39) 562-570.	52	88	2009	9	10.1111/j.1365-2222.2008.03191.x	Allergy; Immunology
Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence. Childhood asthma is frequently perceived as a disease with uniform clinical pathways. This perception might be an oversimplification. The aim of the present study was to investigate the incidence and natural course of wheeze over the first 13 yrs of life and analyse the risk factors predicting wheeze at 11-13 yrs of age. The Multicentre Allergy Study, a German birth cohort, recruited 1,314 children in 1990. Physical examinations, interviews on atopic diseases, immunoglobulin (Ig)E and lung function tests were performed up to 13 yrs of age. Complete data on the course of wheeze were available for 441 children. It was found that incidence of wheezing declined with age. The first wheezing episode was reported by 299 9 and 9% of participants at <= 3 (early wheezers), 3-6 (late wheezers), and >6 yrs (very late wheezers) of age, respectively. Wheezing at the age of 13 yrs was associated with parental atopy, and with IgE sensitisation to common allergens, elevated total IgE and exposure to high levels of indoor allergens in early life. All these associations were remarkably stronger among early wheezers than among early nonwheezers. In conclusion, the relevance of an early expression of atopy as a predictor of wheezing at age 13 yrs declines with increasing age of wheezing onset.. asthma| atopic dermatitis| children| epidemiology| prediction of persistence| wheezing|birth cohort| inhaled corticosteroids| asthma-treatment| follow-up| high-risk| children| prevention| life| age| sensitization.	SEP-2008	asthma| atopic dermatitis| children| epidemiology| prediction of persistence| wheezing|birth cohort| inhaled corticosteroids| asthma-treatment| follow-up| high-risk| children| prevention| life| age| sensitization	Matricardi, PM; Illi, S; Gruber, C; Keil, T; Nickel, R; Wahn, U; Lau, S	Wheezing in childhood: incidence, longitudinal patterns and factors predicting persistence		EUROPEAN RESPIRATORY JOURNAL	asthma; atopic dermatitis; children; epidemiology; prediction of persistence; wheezing	BIRTH COHORT; INHALED CORTICOSTEROIDS; ASTHMA-TREATMENT; FOLLOW-UP; HIGH-RISK; CHILDREN; PREVENTION; LIFE; AGE; SENSITIZATION	Childhood asthma is frequently perceived as a disease with uniform clinical pathways. This perception might be an oversimplification. The aim of the present study was to investigate the incidence and natural course of wheeze over the first 13 yrs of life and analyse the risk factors predicting wheeze at 11-13 yrs of age. The Multicentre Allergy Study, a German birth cohort, recruited 1,314 children in 1990. Physical examinations, interviews on atopic diseases, immunoglobulin (Ig)E and lung function tests were performed up to 13 yrs of age. Complete data on the course of wheeze were available for 441 children. It was found that incidence of wheezing declined with age. The first wheezing episode was reported by 299 9 and 9% of participants at <= 3 (early wheezers), 3-6 (late wheezers), and >6 yrs (very late wheezers) of age, respectively. Wheezing at the age of 13 yrs was associated with parental atopy, and with IgE sensitisation to common allergens, elevated total IgE and exposure to high levels of indoor allergens in early life. All these associations were remarkably stronger among early wheezers than among early nonwheezers. In conclusion, the relevance of an early expression of atopy as a predictor of wheezing at age 13 yrs declines with increasing age of wheezing onset.	25	88	2008	8	10.1183/09031936.00066307	Respiratory System
Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone. Background: Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART (R)) improves asthma control compared with fixed-dose inhaled corticosteroid/ long-acting beta(2)-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose satmeterol/fluticasone (Seretide(TM)) plus a short-acting beta(2)-agonist (SABA). Methods: Patients (N = 2309) with symptomatic asthma (aged _> 12 years; forced expiratory volume in 1 s > 50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 mu g two inhalations twice daily and as needed, or one inhalation of salmeterot/fluticasone 50/500 mu g twice daily plus terbutaline as needed, for 6 months. Results: Time to first severe exacerbation, the pre-specified primary outcome, was not significantly prolonged (risk ratio 0.82; 95% confidence interval 0.63, 1.05). Budesonide/ formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients/year (P=0.039), and exacerbations requiring hospitalisation/ emergency room (ER) treatment from 13 to 9 events/100 patients/year (P=0.046). The treatments showed no difference in measures of lung function or asthma symptoms. The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy (792 mu g/day budesonide [1238 mu g/day beclomethasone dipropionate (BDP) equivalent] versus 1000 mu g/day fluticasone [2000 mu g/day BDP equivalent] with salmeterol/ fluticasone therapy; P<0.0001). Both treatments were well tolerated. Conclusion: In the treatment of uncontrolled asthma, budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA. This benefit is achieved with substantially less ICS exposure. (C) 2007 Published by Elsevier Ltd.. asthma control| exacerbations| hospitatisations| combination therapy| maintenance plus as needed|randomized controlled-trial| inhaled budesonide| single inhaler| formoterol| exacerbations| combination| therapy| salmeterol| metaanalysis| medication.	DEC-2007	asthma control| exacerbations| hospitatisations| combination therapy| maintenance plus as needed|randomized controlled-trial| inhaled budesonide| single inhaler| formoterol| exacerbations| combination| therapy| salmeterol| metaanalysis| medication	Bousquet, J; Boulet, LP; Peters, MJ; Magnussen, H; Quiralte, J; Martinez-Aguilarf, NE; Carlsheimer, A	Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone		RESPIRATORY MEDICINE	asthma control; exacerbations; hospitatisations; combination therapy; maintenance plus as needed	RANDOMIZED CONTROLLED-TRIAL; INHALED BUDESONIDE; SINGLE INHALER; FORMOTEROL; EXACERBATIONS; COMBINATION; THERAPY; SALMETEROL; METAANALYSIS; MEDICATION	Background: Budesonide/formoterol maintenance and reliever therapy (Symbicort SMART (R)) improves asthma control compared with fixed-dose inhaled corticosteroid/ long-acting beta(2)-agonist (ICS/LABA) regimens, but its efficacy has not been assessed in comparison with sustained high-dose satmeterol/fluticasone (Seretide(TM)) plus a short-acting beta(2)-agonist (SABA). Methods: Patients (N = 2309) with symptomatic asthma (aged _> 12 years; forced expiratory volume in 1 s > 50% predicted), who had experienced an asthma exacerbation in the previous year, were randomised to receive budesonide/formoterol 160/4.5 mu g two inhalations twice daily and as needed, or one inhalation of salmeterot/fluticasone 50/500 mu g twice daily plus terbutaline as needed, for 6 months. Results: Time to first severe exacerbation, the pre-specified primary outcome, was not significantly prolonged (risk ratio 0.82; 95% confidence interval 0.63, 1.05). Budesonide/ formoterol maintenance and reliever therapy reduced total exacerbations from 31 to 25 events/100 patients/year (P=0.039), and exacerbations requiring hospitalisation/ emergency room (ER) treatment from 13 to 9 events/100 patients/year (P=0.046). The treatments showed no difference in measures of lung function or asthma symptoms. The mean dose of ICS received was lower using budesonide/formoterol maintenance and reliever therapy (792 mu g/day budesonide [1238 mu g/day beclomethasone dipropionate (BDP) equivalent] versus 1000 mu g/day fluticasone [2000 mu g/day BDP equivalent] with salmeterol/ fluticasone therapy; P<0.0001). Both treatments were well tolerated. Conclusion: In the treatment of uncontrolled asthma, budesonide/formoterol maintenance and reliever therapy reduces the incidence of severe asthma exacerbations and hospitalisation/ER treatment with similar daily symptom control compared with sustained high-dose salmeterol/fluticasone plus SABA. This benefit is achieved with substantially less ICS exposure. (C) 2007 Published by Elsevier Ltd.	35	88	2007	10	10.1016/j.rmed.2007.07.014	Cardiovascular System & Cardiology; Respiratory System
Risk factors associated with persistent airflow limitation in severe or difficult-to-treat asthma. Background: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study is among the largest to assess persistent airflow limitation and the first to evaluate a wide range of potential risk factors in high-risk patients with severe or difficult-to-treat asthma. A better understanding is needed regarding factors associated with persistent airway obstruction; this study was performed to determine demographic and clinical characteristics associated with persistent airflow limitation. Methods: Data from adult patients (>= 18 years old) with severe or difficult-to-treat asthma were evaluated. Patients with COPD, obesity with a restrictive respiratory pattern, or a >= 30 pack-year history of smoking were excluded. Patients with persistent airflow limitation (postbronchodilator FEV1/FVC ratio <= 70% at two annual consecutive visits) and normal postbronchodilator FEV1/ FVC ratio (75 to 85%) were compared. Multivariate analysis identified factors independently associated with persistent airflow limitation. Results: Of 1,017 patients, 612 patients (60%) showed evidence of persistent airflow limitation. Risk factors were as follows: older age (odds ratio [OR] per 10 years, 1.4; 95 % confidence interval [CI], 1.3 to 1.6); male gender (OR, 4.5; 95% CI, 2.3 to 8.5); black ethnicity (OR, 2.2; 95% CI, 1.3 to 3.8); current or past smoking (OR, 3.9; 95% CI, 1.8 to 8.6; and OR, 1.6; 95% CI, 1.2 to 2.3, respectively); aspirin sensitivity (OR, 1.5; 95% CI, 1.0 to 2.4); and longer asthma duration (OR per 10 years, 1.6; 95% CI, 1.4 to 1.8). Protective factors were Hispanic ethnicity, higher education, family history of atopic dermatitis, pet(s) in the home, and dust sensitivity. Conclusions: Persistent airflow limitation is prevalent in patients with severe or difficult-to-treat asthma and is associated with identifiable clinical and demographic characteristics.. airway remodeling| difficult-to-treat asthma| irreversible airway obstruction| persistent airflow limitation| severe asthma|ethnically diverse populations| treatment regimens tenor| lung-function| beta(2)-adrenergic receptor| computed-tomography| susceptibility loci| cigarette-smoking| natural-history| wall thickness| mild asthma.	DEC-2007	airway remodeling| difficult-to-treat asthma| irreversible airway obstruction| persistent airflow limitation| severe asthma|ethnically diverse populations| treatment regimens tenor| lung-function| beta(2)-adrenergic receptor| computed-tomography| susceptibility loci| cigarette-smoking| natural-history| wall thickness| mild asthma	Lee, JH; Haselkorn, T; Borish, L; Rasouliyan, L; Chipps, BE; Wenzel, SE	Risk factors associated with persistent airflow limitation in severe or difficult-to-treat asthma		CHEST	airway remodeling; difficult-to-treat asthma; irreversible airway obstruction; persistent airflow limitation; severe asthma	ETHNICALLY DIVERSE POPULATIONS; TREATMENT REGIMENS TENOR; LUNG-FUNCTION; BETA(2)-ADRENERGIC RECEPTOR; COMPUTED-TOMOGRAPHY; SUSCEPTIBILITY LOCI; CIGARETTE-SMOKING; NATURAL-HISTORY; WALL THICKNESS; MILD ASTHMA	Background: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study is among the largest to assess persistent airflow limitation and the first to evaluate a wide range of potential risk factors in high-risk patients with severe or difficult-to-treat asthma. A better understanding is needed regarding factors associated with persistent airway obstruction; this study was performed to determine demographic and clinical characteristics associated with persistent airflow limitation. Methods: Data from adult patients (>= 18 years old) with severe or difficult-to-treat asthma were evaluated. Patients with COPD, obesity with a restrictive respiratory pattern, or a >= 30 pack-year history of smoking were excluded. Patients with persistent airflow limitation (postbronchodilator FEV1/FVC ratio <= 70% at two annual consecutive visits) and normal postbronchodilator FEV1/ FVC ratio (75 to 85%) were compared. Multivariate analysis identified factors independently associated with persistent airflow limitation. Results: Of 1,017 patients, 612 patients (60%) showed evidence of persistent airflow limitation. Risk factors were as follows: older age (odds ratio [OR] per 10 years, 1.4; 95 % confidence interval [CI], 1.3 to 1.6); male gender (OR, 4.5; 95% CI, 2.3 to 8.5); black ethnicity (OR, 2.2; 95% CI, 1.3 to 3.8); current or past smoking (OR, 3.9; 95% CI, 1.8 to 8.6; and OR, 1.6; 95% CI, 1.2 to 2.3, respectively); aspirin sensitivity (OR, 1.5; 95% CI, 1.0 to 2.4); and longer asthma duration (OR per 10 years, 1.6; 95% CI, 1.4 to 1.8). Protective factors were Hispanic ethnicity, higher education, family history of atopic dermatitis, pet(s) in the home, and dust sensitivity. Conclusions: Persistent airflow limitation is prevalent in patients with severe or difficult-to-treat asthma and is associated with identifiable clinical and demographic characteristics.	38	88	2007	8	10.1378/chest.07-0713	General & Internal Medicine; Respiratory System
Exposure to the fish parasite Anisakis causes allergic airway hyperreactivity and dermatitis. Background: Several case reports show allergy and anaphylactic reactions to the fish parasite Anisakis in the domestic and occupational setting. Further research is needed on the prevalence and mechanisms of disease. Objective: To determine the prevalence of Anisakis sensitization and related symptoms among workers in 2 fish-processing factories, and to use gene-deficient mice to determine the working mechanisms of Anisakis allergy. Methods: A modified version of the European Community Respiratory Health Survey was used to interview 578 South African fish-processing workers. Sensitization to Anisakis, seafood, and common aeroallergens was determined by skin prick test. Lung function was measured by spirometry and methacholine challenge. Serum eicosapentaenoic acid levels were used as an index of seafood consumption. Sensitized wildtype, IL-4, or IL-4 receptor alpha-deficient mice were challenged orally with Anisakis extract. Allergic reactions, lung pathology, antibodies, cytokines, mast cell proteases, and histamine were evaluated. Results: The prevalence of sensitization to Anisakis was higher than the prevalence of sensitization to fish (8% vs 6%). Anisakis-specific IgE reactivity was associated with bronchial hyperreactivity and dermatitis, and significantly increased with fish consumption. In mice, Anisakis infective larvae (1,3) induced a striking T(H)2/type 2 response. Food-allergic-type reactions induced by oral challenge with Anisakis extract were absent in IL-4 receptor a knockout mice. Conclusion: Anisakis sensitization in fish-processing workers is associated with allergic symptoms and correlates with high levels of fish consumption. Anisakis proteins induce allergic reactions in sensitized mice by IL-4/IL-13-mediated mechanisms. Clinical implications: Anisakis allergy should be considered in fish-processing workers with allergic symptoms.. anisakis| nematode| parasitc| gene-deficient mice| food allergy| dermatitis| asthma| occupational allergy| il4| il-13|leishmania-major infection| food allergy| gastroallergic anisakiasis| larval antigens| seafood allergy| united-states| t-cells| simplex| asthma| responses.	MAY-2006	anisakis| nematode| parasitc| gene-deficient mice| food allergy| dermatitis| asthma| occupational allergy| il4| il-13|leishmania-major infection| food allergy| gastroallergic anisakiasis| larval antigens| seafood allergy| united-states| t-cells| simplex| asthma| responses	Nieuwenhuizen, N; Lopata, AL; Jeebhay, MLF; Herbert, DR; Robins, TG; Brombacher, F	Exposure to the fish parasite Anisakis causes allergic airway hyperreactivity and dermatitis		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	anisakis; nematode; parasitc; gene-deficient mice; food allergy; dermatitis; asthma; occupational allergy; IL4; IL-13	LEISHMANIA-MAJOR INFECTION; FOOD ALLERGY; GASTROALLERGIC ANISAKIASIS; LARVAL ANTIGENS; SEAFOOD ALLERGY; UNITED-STATES; T-CELLS; SIMPLEX; ASTHMA; RESPONSES	Background: Several case reports show allergy and anaphylactic reactions to the fish parasite Anisakis in the domestic and occupational setting. Further research is needed on the prevalence and mechanisms of disease. Objective: To determine the prevalence of Anisakis sensitization and related symptoms among workers in 2 fish-processing factories, and to use gene-deficient mice to determine the working mechanisms of Anisakis allergy. Methods: A modified version of the European Community Respiratory Health Survey was used to interview 578 South African fish-processing workers. Sensitization to Anisakis, seafood, and common aeroallergens was determined by skin prick test. Lung function was measured by spirometry and methacholine challenge. Serum eicosapentaenoic acid levels were used as an index of seafood consumption. Sensitized wildtype, IL-4, or IL-4 receptor alpha-deficient mice were challenged orally with Anisakis extract. Allergic reactions, lung pathology, antibodies, cytokines, mast cell proteases, and histamine were evaluated. Results: The prevalence of sensitization to Anisakis was higher than the prevalence of sensitization to fish (8% vs 6%). Anisakis-specific IgE reactivity was associated with bronchial hyperreactivity and dermatitis, and significantly increased with fish consumption. In mice, Anisakis infective larvae (1,3) induced a striking T(H)2/type 2 response. Food-allergic-type reactions induced by oral challenge with Anisakis extract were absent in IL-4 receptor a knockout mice. Conclusion: Anisakis sensitization in fish-processing workers is associated with allergic symptoms and correlates with high levels of fish consumption. Anisakis proteins induce allergic reactions in sensitized mice by IL-4/IL-13-mediated mechanisms. Clinical implications: Anisakis allergy should be considered in fish-processing workers with allergic symptoms.	52	88	2006	8	10.1016/j.jaci.2005.12.1357	Allergy; Immunology
Anti-IgE for chronic asthma in adults and children. Background Omalizumab is a recombinant humanised monoclonal antibody directed against immunoglobulin E (anti-IgE) to inhibit the immune system's response to allergen exposure. Omalizumab is directed against the binding site of IgE for its high affinity Fc receptor. It prevents free serum IgE from attaching to mast cells and other effector cells and prevents IgE mediated inflammatory changes. Objectives To determine the efficacy of anti-IgE compared with placebo in patients with allergic asthma. Search strategy We searched the Cochrane Airways Group Asthma trials register for potentially relevant studies (February 2006). Selection criteria Randomised controlled trials examining anti-IgE administered in any manner for any duration. Trials with co-interventions were included as long as they were the same in each arm. Data collection and analysis Two reviewers independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature (inhaled, intravenous and subcutaneous injection). Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. Main results Fourteen trials (15 group comparisons) were included in the review, contributing a total of 3143 mild to severe allergic asthmatic participants with high levels of IgE. Treatment with intravenous and subcutaneous Omalizumab significantly reduced free IgE compared with placebo. Omalizumab led to a significant reduction in inhaled steroid (ICS) consumption compared with placebo (-119 mcg/day (95% CI -154 to -83, three trials)). There were significant increases in the number of participants who were able to reduce ICS by over 50% (odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10 (four trials)); or completely withdraw their daily ICS intake (OR 2.50 (95% CI 2.00 to 3.13; four trials)). Participants treated with Omalizumab were less likely to suffer an asthma exacerbation with treatment as an adjunct to ICS (OR 0.52, 95% CI 0.41 to 0.65, five trials), or as an ICS tapering agent (OR 0.47, 95% CI 0.37 to 0.60, four trials). Authors' conclusions Omalizumab was significantly more effective than placebo at increasing the numbers of patients who were able to reduce or withdraw their inhaled steroids, but the clinical value of the reduction in steroid consumption has be considered in the light of the high cost of Omalizumab. The impressive placebo effects observed in control groups bring into question the true effect of Omalizumab. Omalizumab was effective in reducing asthma exacerbations as an adjunctive therapy to inhaled steroids, and during steroid tapering phases of clinical trials. Omalizumab was generally well tolerated, although there were more injection site reactions with Omalizumab. Patient and physician assessments of the drug were positive. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS.. anti-asthmatic agents [therapeutic use]| antibodies, anti-idiotypic [*therapeutic use]| antibodies, monoclonal [*therapeutic use]| asthma [*drug therapy| immunology]| chronic disease| immunoglobulin e [blood| immunology]| randomized controlled trials|severe allergic-asthma| quality-of-life| antiimmunoglobulin-e antibody| humanized monoclonal-antibody| complex-formation| serum ige| e therapy| omalizumab| efficacy| disease.	2006	anti-asthmatic agents [therapeutic use]| antibodies, anti-idiotypic [*therapeutic use]| antibodies, monoclonal [*therapeutic use]| asthma [*drug therapy| immunology]| chronic disease| immunoglobulin e [blood| immunology]| randomized controlled trials|severe allergic-asthma| quality-of-life| antiimmunoglobulin-e antibody| humanized monoclonal-antibody| complex-formation| serum ige| e therapy| omalizumab| efficacy| disease	Walker, S; Monteil, M; Phelan, K; Lasserson, TJ; Walters, EH	Anti-IgE for chronic asthma in adults and children		COCHRANE DATABASE OF SYSTEMATIC REVIEWS	anti-asthmatic agents [therapeutic use]; antibodies, anti-idiotypic [*therapeutic use]; antibodies, monoclonal [*therapeutic use]; asthma [*drug therapy; immunology]; chronic disease; immunoglobulin E [blood; immunology]; randomized controlled trials	SEVERE ALLERGIC-ASTHMA; QUALITY-OF-LIFE; ANTIIMMUNOGLOBULIN-E ANTIBODY; HUMANIZED MONOCLONAL-ANTIBODY; COMPLEX-FORMATION; SERUM IGE; E THERAPY; OMALIZUMAB; EFFICACY; DISEASE	Background Omalizumab is a recombinant humanised monoclonal antibody directed against immunoglobulin E (anti-IgE) to inhibit the immune system's response to allergen exposure. Omalizumab is directed against the binding site of IgE for its high affinity Fc receptor. It prevents free serum IgE from attaching to mast cells and other effector cells and prevents IgE mediated inflammatory changes. Objectives To determine the efficacy of anti-IgE compared with placebo in patients with allergic asthma. Search strategy We searched the Cochrane Airways Group Asthma trials register for potentially relevant studies (February 2006). Selection criteria Randomised controlled trials examining anti-IgE administered in any manner for any duration. Trials with co-interventions were included as long as they were the same in each arm. Data collection and analysis Two reviewers independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature (inhaled, intravenous and subcutaneous injection). Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. Main results Fourteen trials (15 group comparisons) were included in the review, contributing a total of 3143 mild to severe allergic asthmatic participants with high levels of IgE. Treatment with intravenous and subcutaneous Omalizumab significantly reduced free IgE compared with placebo. Omalizumab led to a significant reduction in inhaled steroid (ICS) consumption compared with placebo (-119 mcg/day (95% CI -154 to -83, three trials)). There were significant increases in the number of participants who were able to reduce ICS by over 50% (odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10 (four trials)); or completely withdraw their daily ICS intake (OR 2.50 (95% CI 2.00 to 3.13; four trials)). Participants treated with Omalizumab were less likely to suffer an asthma exacerbation with treatment as an adjunct to ICS (OR 0.52, 95% CI 0.41 to 0.65, five trials), or as an ICS tapering agent (OR 0.47, 95% CI 0.37 to 0.60, four trials). Authors' conclusions Omalizumab was significantly more effective than placebo at increasing the numbers of patients who were able to reduce or withdraw their inhaled steroids, but the clinical value of the reduction in steroid consumption has be considered in the light of the high cost of Omalizumab. The impressive placebo effects observed in control groups bring into question the true effect of Omalizumab. Omalizumab was effective in reducing asthma exacerbations as an adjunctive therapy to inhaled steroids, and during steroid tapering phases of clinical trials. Omalizumab was generally well tolerated, although there were more injection site reactions with Omalizumab. Patient and physician assessments of the drug were positive. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS.	86	88	2006	94	10.1002/14651858.CD003559.pub3	General & Internal Medicine
Effects of food processing on the stability of food allergens. The ubiquitous presence of allergens in the human food supply coupled with increased awareness of food allergies warrants undertaking appropriate preventive measures to protect sensitive consumers from unwanted exposure to offending food allergens. Attempts to reduce or eliminate food allergenicity through food processing have met with mixed results. The rationale for using food processing to reduce/eliminate allergenicity and limitations to using this approach are discussed. (C) 2005 Elsevier Inc. All rights reserved.. food allergy| processing| stability| epitope|double-blind| proteins| challenge| fish| kiwi| nut.	SEP-2005	food allergy| processing| stability| epitope|double-blind| proteins| challenge| fish| kiwi| nut	Sathe, SK; Teuber, SS; Roux, KH	Effects of food processing on the stability of food allergens		BIOTECHNOLOGY ADVANCES	food allergy; processing; stability; epitope	DOUBLE-BLIND; PROTEINS; CHALLENGE; FISH; KIWI; NUT	The ubiquitous presence of allergens in the human food supply coupled with increased awareness of food allergies warrants undertaking appropriate preventive measures to protect sensitive consumers from unwanted exposure to offending food allergens. Attempts to reduce or eliminate food allergenicity through food processing have met with mixed results. The rationale for using food processing to reduce/eliminate allergenicity and limitations to using this approach are discussed. (C) 2005 Elsevier Inc. All rights reserved.	19	88	2005	7	10.1016/j.biotechadv.2005.05.008	Biotechnology & Applied Microbiology
Genome screen for asthma and bronchial hyperresponsiveness: Interactions with passive smoke exposure. Background: Asthma is a common respiratory disease caused by the interaction of genetic susceptibility and exposure to various environmental factors. Passive smoke exposure, characterized by parental smoking, has been shown to be a risk factor for the development of atopy and asthma. Objective: We sought to perform a genome-wide linkage screen for asthma and bronchial hyperresponsiveness (BHR) and to determine the influence of passive tobacco smoke exposure during childhood on the results of genetic linkage studies to investigate gene-environment interactions. Methods: A genome-wide linkage screen for asthma and BHR was performed in 200 families ascertained through a parent with asthma. Analyses were performed separately for the entire sample and for the smoking-exposed and nonexposed families. Results: For asthma and BHR, the strongest evidence for linkage was observed for chromosomes 3p and 5q. The families in which the children were exposed to passive smoking accounted for the evidence for linkage of BHR to 5q (P < .001), but evidence for linkage to 3p was found in both sets of families. Similar results were observed for asthma. However, there was no observed difference in the frequency of asthma or BHR in the offspring from the smoke-exposed compared with the nonexposed families. Conclusion: The results from this study demonstrate that the influence of susceptibility genes for a common disease such as asthma might not be apparent unless there is the appropriate exposure to environmental stimuli, such as passive exposure to cigarette smoke. This approach should be useful for identification of asthma susceptibility genes.. smoking| bronchial hyperresponsiveness| asthma| lung function| linkage| genome-wide sereen|environmental tobacco-smoke| wide search| respiratory symptoms| chromosome 5q31-q33| susceptibility loci| founder population| linkage analysis| lung-function| serum ige| gene.	JUN-2005	smoking| bronchial hyperresponsiveness| asthma| lung function| linkage| genome-wide sereen|environmental tobacco-smoke| wide search| respiratory symptoms| chromosome 5q31-q33| susceptibility loci| founder population| linkage analysis| lung-function| serum ige| gene	Meyers, DA; Postma, DS; Stine, OC; Koppelman, GH; Ampleford, EJ; Jongepier, H; Howard, TD; Bleecker, ER	Genome screen for asthma and bronchial hyperresponsiveness: Interactions with passive smoke exposure		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	smoking; bronchial hyperresponsiveness; asthma; lung function; linkage; genome-wide sereen	ENVIRONMENTAL TOBACCO-SMOKE; WIDE SEARCH; RESPIRATORY SYMPTOMS; CHROMOSOME 5Q31-Q33; SUSCEPTIBILITY LOCI; FOUNDER POPULATION; LINKAGE ANALYSIS; LUNG-FUNCTION; SERUM IGE; GENE	Background: Asthma is a common respiratory disease caused by the interaction of genetic susceptibility and exposure to various environmental factors. Passive smoke exposure, characterized by parental smoking, has been shown to be a risk factor for the development of atopy and asthma. Objective: We sought to perform a genome-wide linkage screen for asthma and bronchial hyperresponsiveness (BHR) and to determine the influence of passive tobacco smoke exposure during childhood on the results of genetic linkage studies to investigate gene-environment interactions. Methods: A genome-wide linkage screen for asthma and BHR was performed in 200 families ascertained through a parent with asthma. Analyses were performed separately for the entire sample and for the smoking-exposed and nonexposed families. Results: For asthma and BHR, the strongest evidence for linkage was observed for chromosomes 3p and 5q. The families in which the children were exposed to passive smoking accounted for the evidence for linkage of BHR to 5q (P < .001), but evidence for linkage to 3p was found in both sets of families. Similar results were observed for asthma. However, there was no observed difference in the frequency of asthma or BHR in the offspring from the smoke-exposed compared with the nonexposed families. Conclusion: The results from this study demonstrate that the influence of susceptibility genes for a common disease such as asthma might not be apparent unless there is the appropriate exposure to environmental stimuli, such as passive exposure to cigarette smoke. This approach should be useful for identification of asthma susceptibility genes.	39	88	2005	7	10.1016/j.jaci.2005.01.070	Allergy; Immunology
Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. Interleukin (IL)-18 was originally regarded to induce T helper cell (Th)1-related cytokines. In general, factors favoring interferon (IFN)-gamma production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid a background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their role in induction of bronchial asthma. Administration of antigen (Ag) induced both air-way inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, the same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were coadministered with IL-18. Furthermore, mice having received IFN-gamma-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR after intranasal administration of Ag and IL-18. Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.. il-9| il-13| il-18| th1| bronchial asthma|allergen-specific th1| ifn-gamma production| mast-cell| bronchial hyperresponsiveness| monoclonal-antibody| epithelial-cells| il-18 receptor| murine model| asthma| expression.	FEB 16-2004	il-9| il-13| il-18| th1| bronchial asthma|allergen-specific th1| ifn-gamma production| mast-cell| bronchial hyperresponsiveness| monoclonal-antibody| epithelial-cells| il-18 receptor| murine model| asthma| expression	Sugimoto, T; Ishikawa, Y; Yoshimoto, T; Hayashi, N; Fujimoto, J; Nakanishi, K	Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse		JOURNAL OF EXPERIMENTAL MEDICINE	IL-9; IL-13; IL-18; Th1; bronchial asthma	ALLERGEN-SPECIFIC TH1; IFN-GAMMA PRODUCTION; MAST-CELL; BRONCHIAL HYPERRESPONSIVENESS; MONOCLONAL-ANTIBODY; EPITHELIAL-CELLS; IL-18 RECEPTOR; MURINE MODEL; ASTHMA; EXPRESSION	Interleukin (IL)-18 was originally regarded to induce T helper cell (Th)1-related cytokines. In general, factors favoring interferon (IFN)-gamma production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid a background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their role in induction of bronchial asthma. Administration of antigen (Ag) induced both air-way inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, the same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were coadministered with IL-18. Furthermore, mice having received IFN-gamma-expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR after intranasal administration of Ag and IL-18. Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-gamma-expressing Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN-gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor alpha, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL-2, and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.	60	88	2004	11	10.1084/jem.20031368	Immunology; Research & Experimental Medicine
Health effects of mycotoxins: A toxicological overview. Diseases caused by fungi are spread by direct implantation or inhalation of spores. Fungi can cause adverse human health effects to many organ systems. In addition to infection and allergy, fungi can produce mycotoxins and organic chemicals that are responsible for various toxicologic effects. We reviewed the published literature on important mycotoxins and systemic effects of mycotoxins. Scientific literature revealed a linkage between ingesting mycotoxin contaminated food and illness, especially hepatic, gastrointestinal, and carcinogenic diseases. Issues related to mycotoxin exposure, specific diseases, and management are discussed. Although there is agreement that diet is the main source of mycotoxin exposure, specific health effects and risk assessment from indoor nonagricultural exposure are limited by the paucity of scientific evidence currently available. Further research on the health effects of inhaling mycotoxins in indoor settings is needed.. mycotoxins| toxicological| gastrointestinal| fungi| mycotoxicosis| indoor| agricultural|volatile organic mixture| stachybotrys-chartarum| pulmonary hemorrhage| ochratoxin-a| t-2 toxin| trichothecene mycotoxins| esophageal cancer| fungal toxins| cell-lines| exposure.	2004	mycotoxins| toxicological| gastrointestinal| fungi| mycotoxicosis| indoor| agricultural|volatile organic mixture| stachybotrys-chartarum| pulmonary hemorrhage| ochratoxin-a| t-2 toxin| trichothecene mycotoxins| esophageal cancer| fungal toxins| cell-lines| exposure	Fung, F; Clark, RF	Health effects of mycotoxins: A toxicological overview		JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY	mycotoxins; toxicological; gastrointestinal; fungi; mycotoxicosis; indoor; agricultural	VOLATILE ORGANIC MIXTURE; STACHYBOTRYS-CHARTARUM; PULMONARY HEMORRHAGE; OCHRATOXIN-A; T-2 TOXIN; TRICHOTHECENE MYCOTOXINS; ESOPHAGEAL CANCER; FUNGAL TOXINS; CELL-LINES; EXPOSURE	Diseases caused by fungi are spread by direct implantation or inhalation of spores. Fungi can cause adverse human health effects to many organ systems. In addition to infection and allergy, fungi can produce mycotoxins and organic chemicals that are responsible for various toxicologic effects. We reviewed the published literature on important mycotoxins and systemic effects of mycotoxins. Scientific literature revealed a linkage between ingesting mycotoxin contaminated food and illness, especially hepatic, gastrointestinal, and carcinogenic diseases. Issues related to mycotoxin exposure, specific diseases, and management are discussed. Although there is agreement that diet is the main source of mycotoxin exposure, specific health effects and risk assessment from indoor nonagricultural exposure are limited by the paucity of scientific evidence currently available. Further research on the health effects of inhaling mycotoxins in indoor settings is needed.	128	88	2004	18	10.1081/CLT-120030947	Toxicology
Disparities in exposure to air pollution during pregnancy. Previous research shows poorer birth outcomes for racial and ethnic minorities and for persons with low socioeconomic status (SES). We evaluated whether mothers in groups at higher risk for poor birth outcomes live in areas of higher air pollution and whether higher exposure to air pollution contributes to poor birth outcomes. An index representing long-term exposure to criteria air pollutants was matched with birth certificate data at the county level for the United States in 1998-1999. We used linear regression to estimate associations between the air pollution index and maternal race and educational attainment, a marker for SES of the mother, controlling for age, Parity, marital status, and region of the country. Then we used logistic regression models both to estimate likelihood of living in counties with the highest levels of air pollution for different racial groups and by educational attainment, adjusting for other maternal risk factors, and to estimate the effect of living in counties with higher levels of air pollution on preterm delivery and births small for gestational age (SGA). Hispanic, African-American, and Asian/Pacific Islander mothers experienced higher mean levels of air pollution and were more than twice as likely to live in the most polluted counties compared with white mothers after controlling for maternal risk factors, region, and educational status [Hispanic mothers: adjusted odds ratio (AOR) = 4.66; 95% confidence interval (95% CI), 1.92-11.32; African-American mothers: AOR = 2.58; 95% CI, 1.00-6.62; Asian/Pacific Islander mothers: AOR = 2.82; 95% CI, 1.07-7.39]. Educational attainment was not associated with living in counties with highest levels of the air pollution index (AOR = 0.95; 95% CI, 0.40-2.26) after adjusting for maternal risk factors, region of the country, and race/ethnicity. There was a small increase in the odds of preterm delivery (AOR = 1.05; 95% CI, 0.99-1.12) but not SGA (AOR = 0.96; 95% CI, 0.86-1-07) in a county with high air pollution. Additional risk of residing in areas with poor air, quality may exacerbate health problems of infants and children already at increased risk for poor health.. air pollution| birth outcomes| criteria air pollutants| environmental justice|low-birth-weight| emergency room visits| north-american children| united-states| southern california| respiratory symptoms| industrial sources| infant-mortality| acid aerosols| asthma.	JUN-2003	air pollution| birth outcomes| criteria air pollutants| environmental justice|low-birth-weight| emergency room visits| north-american children| united-states| southern california| respiratory symptoms| industrial sources| infant-mortality| acid aerosols| asthma	Woodruff, TJ; Parker, JD; Kyle, AD; Schoendorf, KC	Disparities in exposure to air pollution during pregnancy		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; birth outcomes; criteria air pollutants; environmental justice	LOW-BIRTH-WEIGHT; EMERGENCY ROOM VISITS; NORTH-AMERICAN CHILDREN; UNITED-STATES; SOUTHERN CALIFORNIA; RESPIRATORY SYMPTOMS; INDUSTRIAL SOURCES; INFANT-MORTALITY; ACID AEROSOLS; ASTHMA	Previous research shows poorer birth outcomes for racial and ethnic minorities and for persons with low socioeconomic status (SES). We evaluated whether mothers in groups at higher risk for poor birth outcomes live in areas of higher air pollution and whether higher exposure to air pollution contributes to poor birth outcomes. An index representing long-term exposure to criteria air pollutants was matched with birth certificate data at the county level for the United States in 1998-1999. We used linear regression to estimate associations between the air pollution index and maternal race and educational attainment, a marker for SES of the mother, controlling for age, Parity, marital status, and region of the country. Then we used logistic regression models both to estimate likelihood of living in counties with the highest levels of air pollution for different racial groups and by educational attainment, adjusting for other maternal risk factors, and to estimate the effect of living in counties with higher levels of air pollution on preterm delivery and births small for gestational age (SGA). Hispanic, African-American, and Asian/Pacific Islander mothers experienced higher mean levels of air pollution and were more than twice as likely to live in the most polluted counties compared with white mothers after controlling for maternal risk factors, region, and educational status [Hispanic mothers: adjusted odds ratio (AOR) = 4.66; 95% confidence interval (95% CI), 1.92-11.32; African-American mothers: AOR = 2.58; 95% CI, 1.00-6.62; Asian/Pacific Islander mothers: AOR = 2.82; 95% CI, 1.07-7.39]. Educational attainment was not associated with living in counties with highest levels of the air pollution index (AOR = 0.95; 95% CI, 0.40-2.26) after adjusting for maternal risk factors, region of the country, and race/ethnicity. There was a small increase in the odds of preterm delivery (AOR = 1.05; 95% CI, 0.99-1.12) but not SGA (AOR = 0.96; 95% CI, 0.86-1-07) in a county with high air pollution. Additional risk of residing in areas with poor air, quality may exacerbate health problems of infants and children already at increased risk for poor health.	44	88	2003	6	10.1289/ehp.5317	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Effect of mattress and pillow encasings on children with asthma and house dust mite allergy. Background: House dust mite (HDM) allergy is a frequent cause of allergic asthma in children. Reduction of exposure seems to be the most logical way to treat these patients. Objective: Our aim was to investigate whether mattress and pillow encasings resulted in an effective long-term control of HDM allergen levels, thereby reducing the need for asthma medication in children with asthma and HDM allergy. Methods: In a prospective, double-blind, placebo-controlled study 60 children (age range, 6-15 years) with asthma and HDM allergy were randomized to active (allergy control) or placebo mattress and pillow encasings. After a 2-week baseline period, follow-up was performed every 3 months for I year. During the entire study period, the dose of inhaled steroids was tapered off to the lowest effective dose according to well-defined criteria. Results: Fifty-two patients completed the trial, and 5 were excluded, leaving data from 47 children (26 in the active treatment group and 21 in the placebo group) for analysis. A significant perennial reduction in HDM allergen concentrations was seen only for the active treatment group. Also, a significant decrease in the dose of inhaled steroids (mean, 408 to 227 mug/d; P <.001) was found for the active treatment group only, with significant differences between groups after 9 and 12 months. After 1 year, the dose of inhaled steroids was reduced by at least 50% in significantly more children in the active treatment group than in the placebo group (73% vs 24%, P <.01). Conclusion: Encasing of mattresses and pillows resulted in a significant long-term reduction in HDM allergen concentrations in mattresses and in the need for inhaled steroids in children with asthma and HDM allergy.. mattress encasing| house dust mite allergy| childhood asthma| inhaled steroids|childhood asthma| airborne allergens| avoidance measures| exposure| sensitization| management| antigen.	JAN-2003	mattress encasing| house dust mite allergy| childhood asthma| inhaled steroids|childhood asthma| airborne allergens| avoidance measures| exposure| sensitization| management| antigen	Halken, S; Host, A; Niklassen, U; Hansen, LG; Nielsen, F; Pedersen, S; Osterballe, O; Veggerby, C; Poulsen, LK	Effect of mattress and pillow encasings on children with asthma and house dust mite allergy		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	mattress encasing; house dust mite allergy; childhood asthma; inhaled steroids	CHILDHOOD ASTHMA; AIRBORNE ALLERGENS; AVOIDANCE MEASURES; EXPOSURE; SENSITIZATION; MANAGEMENT; ANTIGEN	Background: House dust mite (HDM) allergy is a frequent cause of allergic asthma in children. Reduction of exposure seems to be the most logical way to treat these patients. Objective: Our aim was to investigate whether mattress and pillow encasings resulted in an effective long-term control of HDM allergen levels, thereby reducing the need for asthma medication in children with asthma and HDM allergy. Methods: In a prospective, double-blind, placebo-controlled study 60 children (age range, 6-15 years) with asthma and HDM allergy were randomized to active (allergy control) or placebo mattress and pillow encasings. After a 2-week baseline period, follow-up was performed every 3 months for I year. During the entire study period, the dose of inhaled steroids was tapered off to the lowest effective dose according to well-defined criteria. Results: Fifty-two patients completed the trial, and 5 were excluded, leaving data from 47 children (26 in the active treatment group and 21 in the placebo group) for analysis. A significant perennial reduction in HDM allergen concentrations was seen only for the active treatment group. Also, a significant decrease in the dose of inhaled steroids (mean, 408 to 227 mug/d; P <.001) was found for the active treatment group only, with significant differences between groups after 9 and 12 months. After 1 year, the dose of inhaled steroids was reduced by at least 50% in significantly more children in the active treatment group than in the placebo group (73% vs 24%, P <.01). Conclusion: Encasing of mattresses and pillows resulted in a significant long-term reduction in HDM allergen concentrations in mattresses and in the need for inhaled steroids in children with asthma and HDM allergy.	22	88	2003	8	10.1067/mai.2003.5	Allergy; Immunology
Early life factors contribute to the decrease in lung function between ages 18 and 40 - The coronary artery risk development in young adults study. Early life factors may influence pulmonary function. We measured forced expiratory volume in 1 second (FEV1) in 1985-1986 and 2, 5, and 10 years later in approximately 4,000 black and white men and women initially aged 18-30 years. We estimated the age pattern of FEV1 according to family smoking status, early diagnosis of asthma, early smoking initiation, adult asthma, and cigarette smoking. FEV1 followed a quadratic pattern from age of peak through age 40. The pattern varied by race and sex. Early smoking initiation was associated with a faster decrease in FEV1. Smoking by family members was related to early life asthma and may have contributed to faster FEV1 decrease by encouraging behaviors such as heavier smoking or earlier smoking initiation. Prevalence of smoking was 28% when no family member smoked, compared with 59% when four or more members smoked. The FEV1 decline was 8.5% in never-smokers without asthma; 10.1% in nonsmoking individuals diagnosed with asthma; and 11.1% in baseline smokers who smoked 15 or more cigarettes per day. The combination of asthma and heavier smoking was synergistic (17.8% decline). This study delineates an increased rate of decline in those with asthma or in those who smoke cigarettes and implicates early life exposures as contributing to the faster rate of FEV1 decline.. lung development| family smoking| smoking| asthma|obstructive pulmonary-disease| forced expiratory volume| tobacco-smoke exposure| respiratory symptoms| cigarette-smoking| reference values| function decline| children| asthma| cardia.	JUL 15-2002	lung development| family smoking| smoking| asthma|obstructive pulmonary-disease| forced expiratory volume| tobacco-smoke exposure| respiratory symptoms| cigarette-smoking| reference values| function decline| children| asthma| cardia	Apostol, GG; Jacobs, DR; Tsai, AW; Crow, RS; Williams, OD; Townsend, MC; Beckett, WS	Early life factors contribute to the decrease in lung function between ages 18 and 40 - The coronary artery risk development in young adults study		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	lung development; family smoking; smoking; asthma	OBSTRUCTIVE PULMONARY-DISEASE; FORCED EXPIRATORY VOLUME; TOBACCO-SMOKE EXPOSURE; RESPIRATORY SYMPTOMS; CIGARETTE-SMOKING; REFERENCE VALUES; FUNCTION DECLINE; CHILDREN; ASTHMA; CARDIA	Early life factors may influence pulmonary function. We measured forced expiratory volume in 1 second (FEV1) in 1985-1986 and 2, 5, and 10 years later in approximately 4,000 black and white men and women initially aged 18-30 years. We estimated the age pattern of FEV1 according to family smoking status, early diagnosis of asthma, early smoking initiation, adult asthma, and cigarette smoking. FEV1 followed a quadratic pattern from age of peak through age 40. The pattern varied by race and sex. Early smoking initiation was associated with a faster decrease in FEV1. Smoking by family members was related to early life asthma and may have contributed to faster FEV1 decrease by encouraging behaviors such as heavier smoking or earlier smoking initiation. Prevalence of smoking was 28% when no family member smoked, compared with 59% when four or more members smoked. The FEV1 decline was 8.5% in never-smokers without asthma; 10.1% in nonsmoking individuals diagnosed with asthma; and 11.1% in baseline smokers who smoked 15 or more cigarettes per day. The combination of asthma and heavier smoking was synergistic (17.8% decline). This study delineates an increased rate of decline in those with asthma or in those who smoke cigarettes and implicates early life exposures as contributing to the faster rate of FEV1 decline.	49	88	2002	7	10.1164/rccm.2007035	General & Internal Medicine; Respiratory System
Mode of delivery and asthma - Is there a connection?. Genetic factors cannot explain the recent rapid increase in the incidence of atopic diseases. The phenomenon has been explained by environmental factors, and there are data for and against the hypothesis that a decline in the pressure of microbial stimulation early in life could be behind the allergy epidemic. Changes have also occurred in maternity care, among them a rise in the caesarean section rate, which could diminish initial microbial exposure and thereby alter T helper 1 cell/T helper-2 cell development and affect the risk of developing atopy. In this study, we sought to establish whether mode of delivery does influence the development of atopic asthma, Finnish 1987 Medical Birth Register (n = 59,927 Live births) information was linked between several national health registers to obtain information on asthma and mode of delivery in children registered. The data were adjusted for maternal age, previous deliveries, child's sex, and birth size. Atopy was evaluated in the second study (Turku Birth Cohort), which involved 219 children born by vaginal delivery (n = 106) or caesarean section (n = 113); history of atopic symptoms was established by questionnaire and a clinical examination was conducted, including skin prick testing and determination of total and allergen-specific I-E in serum, The register study showed the Cumulative incidence of asthma at the age of seven to be significantly higher in children born by caesarean section (4.2%) than in those vaginally delivered (3.3%), the adjusted odds ratio (OR) for confounding variables being 1.21 (1.08-1.36), p < 0.01, In the second study, significantly more positive allergy tests were reported in questionnaires in the caesarean (22%) than in the vaginal delivery group (I M, OR 2.22 (1.06-4.64), p < 0.01, and a trend toward more positive skin prick reactions was documented at clinical examination; 41% versits 29%, OR 1.31 (0.65-2.65), p = 0.11. In conclusion, these results suggest that caesarean section delivery may be associated with an increased prevalence of atopic asthma.. follow-up| birth cohort| children| prevalence| atopy| childhood| infants| life| microflora| health.	JUL-2002	follow-up| birth cohort| children| prevalence| atopy| childhood| infants| life| microflora| health	Kero, J; Gissler, M; Gronlund, MM; Kero, P; Koskinen, O; Hemminki, E; Isolauri, E	Mode of delivery and asthma - Is there a connection?		PEDIATRIC RESEARCH		FOLLOW-UP; BIRTH COHORT; CHILDREN; PREVALENCE; ATOPY; CHILDHOOD; INFANTS; LIFE; MICROFLORA; HEALTH	Genetic factors cannot explain the recent rapid increase in the incidence of atopic diseases. The phenomenon has been explained by environmental factors, and there are data for and against the hypothesis that a decline in the pressure of microbial stimulation early in life could be behind the allergy epidemic. Changes have also occurred in maternity care, among them a rise in the caesarean section rate, which could diminish initial microbial exposure and thereby alter T helper 1 cell/T helper-2 cell development and affect the risk of developing atopy. In this study, we sought to establish whether mode of delivery does influence the development of atopic asthma, Finnish 1987 Medical Birth Register (n = 59,927 Live births) information was linked between several national health registers to obtain information on asthma and mode of delivery in children registered. The data were adjusted for maternal age, previous deliveries, child's sex, and birth size. Atopy was evaluated in the second study (Turku Birth Cohort), which involved 219 children born by vaginal delivery (n = 106) or caesarean section (n = 113); history of atopic symptoms was established by questionnaire and a clinical examination was conducted, including skin prick testing and determination of total and allergen-specific I-E in serum, The register study showed the Cumulative incidence of asthma at the age of seven to be significantly higher in children born by caesarean section (4.2%) than in those vaginally delivered (3.3%), the adjusted odds ratio (OR) for confounding variables being 1.21 (1.08-1.36), p < 0.01, In the second study, significantly more positive allergy tests were reported in questionnaires in the caesarean (22%) than in the vaginal delivery group (I M, OR 2.22 (1.06-4.64), p < 0.01, and a trend toward more positive skin prick reactions was documented at clinical examination; 41% versits 29%, OR 1.31 (0.65-2.65), p = 0.11. In conclusion, these results suggest that caesarean section delivery may be associated with an increased prevalence of atopic asthma.	51	88	2002	6	10.1023/01.PDR.0000017263.01840.F0	Pediatrics
The crystal structure of a major dust mite allergen Der p 2, and its biological implications. The crystal structure of the common house mite (Dermatophagoides sp.) Der p 2 allergen was solved at 2.15 Angstrom resolution using the MAD phasing technique, and refined to an R-factor of 0.209. The refined atomic model, which reveals an immunoglobulin-like tertiary fold, differs in important ways from the previously described NMR structure, because the two beta-sheets are significantly further apart and create an internal cavity, which is occupied by a hydrophobic ligand. This interaction is structurally reminiscent of the binding of a prenyl group by a regulatory protein, the Rho guanine nucleotide exchange inhibitor. The crystal structure suggests that binding of non-polar molecules may be essential to the physiological function of the Der p 2 protein, (C) 2002 Elsevier Science Ltd. All rights reserved.. allergen| asthma| x-ray structure| immunoglobulin fold| hydrophobic cavity|macromolecular structures| immunoglobulin fold| protein| der-p-2| family| rhogdi| binds| dermatophagoides| refinement| asthma.	APR 19-2002	allergen| asthma| x-ray structure| immunoglobulin fold| hydrophobic cavity|macromolecular structures| immunoglobulin fold| protein| der-p-2| family| rhogdi| binds| dermatophagoides| refinement| asthma	Derewenda, U; Li, J; Derewenda, Z; Dauter, Z; Mueller, GA; Rule, GS; Benjamin, DC	The crystal structure of a major dust mite allergen Der p 2, and its biological implications		JOURNAL OF MOLECULAR BIOLOGY	allergen; asthma; X-ray structure; immunoglobulin fold; hydrophobic cavity	MACROMOLECULAR STRUCTURES; IMMUNOGLOBULIN FOLD; PROTEIN; DER-P-2; FAMILY; RHOGDI; BINDS; DERMATOPHAGOIDES; REFINEMENT; ASTHMA	The crystal structure of the common house mite (Dermatophagoides sp.) Der p 2 allergen was solved at 2.15 Angstrom resolution using the MAD phasing technique, and refined to an R-factor of 0.209. The refined atomic model, which reveals an immunoglobulin-like tertiary fold, differs in important ways from the previously described NMR structure, because the two beta-sheets are significantly further apart and create an internal cavity, which is occupied by a hydrophobic ligand. This interaction is structurally reminiscent of the binding of a prenyl group by a regulatory protein, the Rho guanine nucleotide exchange inhibitor. The crystal structure suggests that binding of non-polar molecules may be essential to the physiological function of the Der p 2 protein, (C) 2002 Elsevier Science Ltd. All rights reserved.	32	88	2002	9	10.0000/S0022-2836(02)00027-X	Biochemistry & Molecular Biology
Arthropod allergens and human health. Many species of arthropods are the sources of potent allergens that sensitize and induce IgE-mediated allergic reactions in humans. Most of these arthropod allergens are proteins, and the allergic response mechanism to these allergens is the same as it is for allergens from other sources such as plant pollens, molds, and foods. Aside from ingestion of crustaceans (shrimp, lobster), among arthropods, humans have the greatest contact with insects and mites, and as a result allergies to these two groups of arthropods have been the most frequently reported. Because of the large number of people affected by allergic reactions to stinging insects, cockroaches, and dust mites. Many allergens of these organisms have been extensively studied, purified, and characterized and for some recombinant allergens, produced. Cocktails of these recombinant allergens have the potential for use in diagnosis and immunotherapy. In this chapter, we review the insects and mites that induce allergic reactions. Where the information exists, the immunobiochemical characterization of the allergens and the frequency, of sensitivity or clinical reactivity in the human population are also reviewed. As background, the beginning of this review includes sections that define allergens, explain the allergic reaction mechanism, and describe the methods for naming allergens.. allergic reactions to arthropods| allergic reactions to insects and mites|house-dust-mite| imported fire ant| american periplaneta-americana| cockroach blattella-germanica| antigenic cross-reactivity| ige antibody-responses| amino-acid-sequences| inner-city children| dermatophagoides-pteronyssinus acari| glutathione-s-transferase.	2002	allergic reactions to arthropods| allergic reactions to insects and mites|house-dust-mite| imported fire ant| american periplaneta-americana| cockroach blattella-germanica| antigenic cross-reactivity| ige antibody-responses| amino-acid-sequences| inner-city children| dermatophagoides-pteronyssinus acari| glutathione-s-transferase	Arlian, LG	Arthropod allergens and human health		ANNUAL REVIEW OF ENTOMOLOGY	allergic reactions to arthropods; allergic reactions to insects and mites	HOUSE-DUST-MITE; IMPORTED FIRE ANT; AMERICAN PERIPLANETA-AMERICANA; COCKROACH BLATTELLA-GERMANICA; ANTIGENIC CROSS-REACTIVITY; IGE ANTIBODY-RESPONSES; AMINO-ACID-SEQUENCES; INNER-CITY CHILDREN; DERMATOPHAGOIDES-PTERONYSSINUS ACARI; GLUTATHIONE-S-TRANSFERASE	Many species of arthropods are the sources of potent allergens that sensitize and induce IgE-mediated allergic reactions in humans. Most of these arthropod allergens are proteins, and the allergic response mechanism to these allergens is the same as it is for allergens from other sources such as plant pollens, molds, and foods. Aside from ingestion of crustaceans (shrimp, lobster), among arthropods, humans have the greatest contact with insects and mites, and as a result allergies to these two groups of arthropods have been the most frequently reported. Because of the large number of people affected by allergic reactions to stinging insects, cockroaches, and dust mites. Many allergens of these organisms have been extensively studied, purified, and characterized and for some recombinant allergens, produced. Cocktails of these recombinant allergens have the potential for use in diagnosis and immunotherapy. In this chapter, we review the insects and mites that induce allergic reactions. Where the information exists, the immunobiochemical characterization of the allergens and the frequency, of sensitivity or clinical reactivity in the human population are also reviewed. As background, the beginning of this review includes sections that define allergens, explain the allergic reaction mechanism, and describe the methods for naming allergens.	280	88	2002	39	10.1146/annurev.ento.47.091201.145224	Entomology
Molecular and immunological characterization of arginine kinase from the indianmeal moth, Plodia interpunctella, a novel cross-reactive invertebrate pan-allergen. IgE recognition of indoor allergens represents a major cause of allergic asthma in atopic individuals. We found that 52 of 102 patients suffering from allergic symptoms indoors contained IgE Abs against allergens from the Indianmeal moth (Plodia interpunctella), a ubiquitous food pest. Using serum IgE from a moth-sensitized patient we screened an expression cDNA library constructed from A interpunctella larvae. cDNAs coding for arginine kinase (EC 2.7.3.3), a 40-kDa enzyme commonly occurring in invertebrates that is involved in the storage of such high-energy phosphate bonds as phosphoarginine, were isolated. Recombinant moth arginine kinase, designated Plo i 1, was expressed in Escherichia coli as a histidine-tagged protein with enzymatic activity, and purified to homogeneity by nickel chelate affinity chromatography. Purified recombinant arginine kinase induced specific basophil histamine release and immediate as well as late-phase skin reactions. It reacted with serum IgE from 13 of the 52 (25%) moth-allergic patients and inhibited the binding of allergic patients' IgE to an immunologically related 40-kDa allergen present in house dust mite, cockroach, king prawn, lobster, and mussel. Our results indicate that arginine kinases represent a new class of cross-reactive invertebrate pan-allergens. Recombinant arginine kinase may be used to identify a group of polysensitized indoor allergic patients and for immunotherapy of these individuals.. reaginic sensitivity| cockroach allergen| bronchial-asthma| ige antibodies| silkworm moth| house-dust| sequence| insects| cloning| sites.	NOV 1-2001	reaginic sensitivity| cockroach allergen| bronchial-asthma| ige antibodies| silkworm moth| house-dust| sequence| insects| cloning| sites	Binder, M; Mahler, V; Hayek, B; Sperr, WR; Scholler, M; Prozell, S; Wiedermann, G; Valent, P; Valenta, R; Duchene, M	Molecular and immunological characterization of arginine kinase from the indianmeal moth, Plodia interpunctella, a novel cross-reactive invertebrate pan-allergen		JOURNAL OF IMMUNOLOGY		REAGINIC SENSITIVITY; COCKROACH ALLERGEN; BRONCHIAL-ASTHMA; IGE ANTIBODIES; SILKWORM MOTH; HOUSE-DUST; SEQUENCE; INSECTS; CLONING; SITES	IgE recognition of indoor allergens represents a major cause of allergic asthma in atopic individuals. We found that 52 of 102 patients suffering from allergic symptoms indoors contained IgE Abs against allergens from the Indianmeal moth (Plodia interpunctella), a ubiquitous food pest. Using serum IgE from a moth-sensitized patient we screened an expression cDNA library constructed from A interpunctella larvae. cDNAs coding for arginine kinase (EC 2.7.3.3), a 40-kDa enzyme commonly occurring in invertebrates that is involved in the storage of such high-energy phosphate bonds as phosphoarginine, were isolated. Recombinant moth arginine kinase, designated Plo i 1, was expressed in Escherichia coli as a histidine-tagged protein with enzymatic activity, and purified to homogeneity by nickel chelate affinity chromatography. Purified recombinant arginine kinase induced specific basophil histamine release and immediate as well as late-phase skin reactions. It reacted with serum IgE from 13 of the 52 (25%) moth-allergic patients and inhibited the binding of allergic patients' IgE to an immunologically related 40-kDa allergen present in house dust mite, cockroach, king prawn, lobster, and mussel. Our results indicate that arginine kinases represent a new class of cross-reactive invertebrate pan-allergens. Recombinant arginine kinase may be used to identify a group of polysensitized indoor allergic patients and for immunotherapy of these individuals.	36	88	2001	8		Immunology
Thunderstorm outflows preceding epidemics of asthma during spring and summer. Background-A study was undertaken to assess the importance of thunderstorms as a cause of epidemics of asthma exacerbations and to investigate the underlying mechanism. Methods-A case control study was performed in six towns in south eastern Australia. Epidemic case days (n = 48) and a random sample of control days (n = 191) were identified by reference to the difference between the observed and expected number of emergency department attendances for asthma. The occurrence of thunderstorms, their associated outflows and cold fronts were ascertained, blind to case status, for each of these days. In addition, the relation of hourly pollen counts to automatic weather station data was examined in detail for the period around one severe epidemic of asthma exacerbations. The main outcome measure was the number of epidemics of asthma exacerbations. Results-Thunderstorm outflows were detected on 33% of epidemic days and only 3% of control days (odds ratio 15.0, 95% confidence interval 6.0 to 37.6). The association was strongest in late spring and summer. Detailed examination of one severe epidemic showed that its onset coincided with the arrival of the thunderstorm outflow and a 4-12 fold increase in the ambient concentration of grass pollen grains. Conclusions-These findings are consistent with the hypothesis that some epidemics of exacerbations of asthma are caused by high concentrations of allergenic particles produced by an outflow of colder air, associated with the downdraught from a thunderstorm, sweeping up pollen grains and particles and then concentrating them in a shallow band of air at ground level. This is a common cause of exacerbations of asthma during the pollen season.. asthma| thunderstorms| season|grass-pollen| air-pollution| australia| mortality| england| city.	JUN-2001	asthma| thunderstorms| season|grass-pollen| air-pollution| australia| mortality| england| city	Marks, GB; Colquhoun, JR; Girgis, ST; Koski, MH; Treloar, ABA; Hansen, P; Downs, SH; Car, NG	Thunderstorm outflows preceding epidemics of asthma during spring and summer		THORAX	asthma; thunderstorms; season	GRASS-POLLEN; AIR-POLLUTION; AUSTRALIA; MORTALITY; ENGLAND; CITY	Background-A study was undertaken to assess the importance of thunderstorms as a cause of epidemics of asthma exacerbations and to investigate the underlying mechanism. Methods-A case control study was performed in six towns in south eastern Australia. Epidemic case days (n = 48) and a random sample of control days (n = 191) were identified by reference to the difference between the observed and expected number of emergency department attendances for asthma. The occurrence of thunderstorms, their associated outflows and cold fronts were ascertained, blind to case status, for each of these days. In addition, the relation of hourly pollen counts to automatic weather station data was examined in detail for the period around one severe epidemic of asthma exacerbations. The main outcome measure was the number of epidemics of asthma exacerbations. Results-Thunderstorm outflows were detected on 33% of epidemic days and only 3% of control days (odds ratio 15.0, 95% confidence interval 6.0 to 37.6). The association was strongest in late spring and summer. Detailed examination of one severe epidemic showed that its onset coincided with the arrival of the thunderstorm outflow and a 4-12 fold increase in the ambient concentration of grass pollen grains. Conclusions-These findings are consistent with the hypothesis that some epidemics of exacerbations of asthma are caused by high concentrations of allergenic particles produced by an outflow of colder air, associated with the downdraught from a thunderstorm, sweeping up pollen grains and particles and then concentrating them in a shallow band of air at ground level. This is a common cause of exacerbations of asthma during the pollen season.	19	88	2001	4	10.1136/thorax.56.6.468	Respiratory System
Role of NF kappa B in antigen presentation and development of regulatory T cells elucidated by treatment of dendritic cells with the proteasome inhibitor PSI. Dendritic cells (DC) are the most potent antigen-presenting cells for naive T cells, due to their high expression of MHC and costimulatory molecules, but relatively little is known about the biochemical pathways that regulate this function. We used the proteasome inhibitor N-benzyloxycarbonyl-IIe-Glu(O-tert-butyl)-Ala-leucinal (PSI) to demonstrate that DC antigen presentation is NF kappaB dependent. As PSI is not a specific inhibitor of NF kappaB, we reproduced this finding using a very specific approach, namely adenoviral gene transfer of I kappaB alpha, the naturally occurring inhibitor of NF kappaB. The mechanism for this inhibition of DC antigen presentation involves at least three aspects of antigen presenting function: down-regulation of HLA class II, down-regulation of CD86, and inhibition of the immunostimulatory cytokines IL-12 and TNF-alpha. In the light of the marked down-regulation of antigen-presentation cell function, it was of interest to investigate what effects exposure to PSI-treated DC might have on T cell function. It was found that immunological tolerance was induced, as challenge of T cells previously exposed to PSI-treated DC, with normal DG from the same donor did not restore their response, despite the presence of viable T cells. There were also changes in T cell surface markers, with down-regulation of CD3 and CD25 expression, and inhibition of the production of Th1 cytokines like IL-2 and IFN-gamma. These results demonstrates that NF kappaB is an effective target for blocking DC antigen presentation and inhibiting T cell-dependent immune responses, and this has implications for the development of therapeutic agents for use in multiple conditions, including transplantation, allergy and autoimmune diseases.. antigen presentation| nf kappa b| tolerance|necrosis-factor-alpha| proinflammatory cytokines| functional-heterogeneity| blood monocytes| activation| tolerance| induction| expression| apoptosis| unresponsiveness.	JUN-2001	antigen presentation| nf kappa b| tolerance|necrosis-factor-alpha| proinflammatory cytokines| functional-heterogeneity| blood monocytes| activation| tolerance| induction| expression| apoptosis| unresponsiveness	Yoshimura, S; Bondeson, J; Brennan, FM; Foxwell, BMJ; Feldmann, M	Role of NF kappa B in antigen presentation and development of regulatory T cells elucidated by treatment of dendritic cells with the proteasome inhibitor PSI		EUROPEAN JOURNAL OF IMMUNOLOGY	antigen presentation; NF kappa B; tolerance	NECROSIS-FACTOR-ALPHA; PROINFLAMMATORY CYTOKINES; FUNCTIONAL-HETEROGENEITY; BLOOD MONOCYTES; ACTIVATION; TOLERANCE; INDUCTION; EXPRESSION; APOPTOSIS; UNRESPONSIVENESS	Dendritic cells (DC) are the most potent antigen-presenting cells for naive T cells, due to their high expression of MHC and costimulatory molecules, but relatively little is known about the biochemical pathways that regulate this function. We used the proteasome inhibitor N-benzyloxycarbonyl-IIe-Glu(O-tert-butyl)-Ala-leucinal (PSI) to demonstrate that DC antigen presentation is NF kappaB dependent. As PSI is not a specific inhibitor of NF kappaB, we reproduced this finding using a very specific approach, namely adenoviral gene transfer of I kappaB alpha, the naturally occurring inhibitor of NF kappaB. The mechanism for this inhibition of DC antigen presentation involves at least three aspects of antigen presenting function: down-regulation of HLA class II, down-regulation of CD86, and inhibition of the immunostimulatory cytokines IL-12 and TNF-alpha. In the light of the marked down-regulation of antigen-presentation cell function, it was of interest to investigate what effects exposure to PSI-treated DC might have on T cell function. It was found that immunological tolerance was induced, as challenge of T cells previously exposed to PSI-treated DC, with normal DG from the same donor did not restore their response, despite the presence of viable T cells. There were also changes in T cell surface markers, with down-regulation of CD3 and CD25 expression, and inhibition of the production of Th1 cytokines like IL-2 and IFN-gamma. These results demonstrates that NF kappaB is an effective target for blocking DC antigen presentation and inhibiting T cell-dependent immune responses, and this has implications for the development of therapeutic agents for use in multiple conditions, including transplantation, allergy and autoimmune diseases.	49	88	2001	11	10.1002/1521-4141(200106)31:6<1883::AID-IMMU1883>3.0.CO;2-V	Immunology
Exhaled nitric oxide in patients with asthma - Association with NOS1 genotype. An increased concentration of nitric oxide (NO) in exhaled air (FENO) is now recognized as a critical component of the asthmatic phenotype. When we identified patients with asthma on the basis of a standard case definition alone, we found that they were remarkably heterogeneous with respect to their FENO. However, when we included genotype at a prominent asthma candidate gene (i.e., NOS1) in the case definition, and determined the number of AAT repeats in intron 20, we identified a remarkably homogenous cohort of patients with respect to FENO. Both mean FENO (p = 0.00008) and variability around the mean (p = 0.000002) were significantly lower in asthmatic individuals with a high number (greater than or equal to 12) of AAT repeats at this locus than in those with fewer repeats. These data provide a biologically tenable link between genotype at a candidate gene in a region of linkage, NOS1, and an important component of the asthmatic phenotype, FENO. We show that addition of NOS1 genotype to the case definition of asthma allows the identification of a uniform cohort of patients, with respect to FENO, that would have been indistinguishable by other physiologic criteria. Our isolation of this homogenous cohort of patients ties together the well-established associations among asthma, increased concentrations of NO in the exhaled air of asthmatic individuals, and variations of trinucleotide repeat sequences as identified in several neurologic conditions.. synthase gene nos1| apolipoprotein-e| population| polymorphisms| inflammation| mutations| disorders| linkage| markers| locus.	DEC-2000	synthase gene nos1| apolipoprotein-e| population| polymorphisms| inflammation| mutations| disorders| linkage| markers| locus	Wechsler, ME; Grasemann, H; Deykin, A; Silverman, EK; Yandava, CN; Israel, E; Wang, M; Drazen, JM	Exhaled nitric oxide in patients with asthma - Association with NOS1 genotype		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		SYNTHASE GENE NOS1; APOLIPOPROTEIN-E; POPULATION; POLYMORPHISMS; INFLAMMATION; MUTATIONS; DISORDERS; LINKAGE; MARKERS; LOCUS	An increased concentration of nitric oxide (NO) in exhaled air (FENO) is now recognized as a critical component of the asthmatic phenotype. When we identified patients with asthma on the basis of a standard case definition alone, we found that they were remarkably heterogeneous with respect to their FENO. However, when we included genotype at a prominent asthma candidate gene (i.e., NOS1) in the case definition, and determined the number of AAT repeats in intron 20, we identified a remarkably homogenous cohort of patients with respect to FENO. Both mean FENO (p = 0.00008) and variability around the mean (p = 0.000002) were significantly lower in asthmatic individuals with a high number (greater than or equal to 12) of AAT repeats at this locus than in those with fewer repeats. These data provide a biologically tenable link between genotype at a candidate gene in a region of linkage, NOS1, and an important component of the asthmatic phenotype, FENO. We show that addition of NOS1 genotype to the case definition of asthma allows the identification of a uniform cohort of patients, with respect to FENO, that would have been indistinguishable by other physiologic criteria. Our isolation of this homogenous cohort of patients ties together the well-established associations among asthma, increased concentrations of NO in the exhaled air of asthmatic individuals, and variations of trinucleotide repeat sequences as identified in several neurologic conditions.	39	88	2000	5		General & Internal Medicine; Respiratory System
Unsuspected pseudophysiologic emphysema in chronic persistent asthma. The current literature emphasizes the role of airway remodeling in chronic persistent asthma and its putative effect on causing fixed expiratory airflow limitation. We studied 18 adults with chronic persistent asthma; 12 men, six women, age 59 +/- 15 yr (mean +/- SD) with fixed expiratory airflow obstruction. We measured lung elastic recoil and examined the mechanism of expiratory airflow limitation. Diaphragmatic strength was also measured in six asthmatics, using both sniff and partially occluded airway technique. All 18 asthmatics had markedly abnormal maximal expiratory flow-volume curves at both high and low lung volumes. Hyperinflation was present at residual volume (RV), FRC, and TLC in all subjects. Diffusing capacity was normal or elevated and lung computed tomography (CT) was normal in all 18 asthmatic subjects. There was a significant loss of lung elastic recoil in three of four asthmatics age 30 to 49, all five age 51 to 60 yr, and seven of nine age 61 to 82 yr. Maximal expiratory airflow limitation in only four elderly asthmatics and only at low lung volumes was due completely to loss of lung elastic recoil. In the others, we estimate the reduction in lung elastic recoil was responsible for 35% reduction in maximal expiratory airflow at 80% of TLC, and 55% at 70% of TLC. Despite hyperinflation, transdiaphragmatic pressures and strength were normal. The mechanisms responsible for loss of lung elastic recoil remain elusive. The high incidence of loss of lung elastic recoil in chronic persistent asthma was unexpected, and its contribution to abnormal lung function needs to be emphasized.. air-flow obstruction| total lung capacity| small-airways| follow-up| diaphragm| disease| hyperinflation| mechanism| muscle| adults.	NOV-2000	air-flow obstruction| total lung capacity| small-airways| follow-up| diaphragm| disease| hyperinflation| mechanism| muscle| adults	Gelb, AF; Zamel, N	Unsuspected pseudophysiologic emphysema in chronic persistent asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		AIR-FLOW OBSTRUCTION; TOTAL LUNG CAPACITY; SMALL-AIRWAYS; FOLLOW-UP; DIAPHRAGM; DISEASE; HYPERINFLATION; MECHANISM; MUSCLE; ADULTS	The current literature emphasizes the role of airway remodeling in chronic persistent asthma and its putative effect on causing fixed expiratory airflow limitation. We studied 18 adults with chronic persistent asthma; 12 men, six women, age 59 +/- 15 yr (mean +/- SD) with fixed expiratory airflow obstruction. We measured lung elastic recoil and examined the mechanism of expiratory airflow limitation. Diaphragmatic strength was also measured in six asthmatics, using both sniff and partially occluded airway technique. All 18 asthmatics had markedly abnormal maximal expiratory flow-volume curves at both high and low lung volumes. Hyperinflation was present at residual volume (RV), FRC, and TLC in all subjects. Diffusing capacity was normal or elevated and lung computed tomography (CT) was normal in all 18 asthmatic subjects. There was a significant loss of lung elastic recoil in three of four asthmatics age 30 to 49, all five age 51 to 60 yr, and seven of nine age 61 to 82 yr. Maximal expiratory airflow limitation in only four elderly asthmatics and only at low lung volumes was due completely to loss of lung elastic recoil. In the others, we estimate the reduction in lung elastic recoil was responsible for 35% reduction in maximal expiratory airflow at 80% of TLC, and 55% at 70% of TLC. Despite hyperinflation, transdiaphragmatic pressures and strength were normal. The mechanisms responsible for loss of lung elastic recoil remain elusive. The high incidence of loss of lung elastic recoil in chronic persistent asthma was unexpected, and its contribution to abnormal lung function needs to be emphasized.	37	88	2000	5		General & Internal Medicine; Respiratory System
Restrictions on smoking at home and urinary cotinine levels among children with asthma. Objectives: The purpose of this study was to determine the extent to which various levels of restrictions on smoking in the home may be associated with children's exposure to environmental tobacco smoke (ETS). Methods: The methodology consisted of a cross-sectional survey involving 249 children with asthma aged 1 to 11 attending hospital outpatient clinics, with at least one parent who smoked, linked to the child's urinary cotinine to creatinine rations (CCR). Results: After adjustment for child's age, mother's smoking status, and total parental daily cigarette consumption, a total ban was associated with significantly lower urinary CCR levels (7.6 nmol/mmol) than bans with exceptions or limited smoking in the home. Where exceptions to bans were made (14.9 nmol/mmol), children's urinary CCR levels were no different from homes in which smoking was allowed in rooms the child rarely frequented (14.1 nmol/mmol). These two intermediate levels of restriction were in turn associated with significantly lower CCR levels than unrestricted smoking in the home (26.0 nmol/mmol). Conclusions: Making exceptions to bans on smoking at home measurably undermines the protective effect of a ban. However, making some exceptions to a ban and limiting smoking to rooms where the child rarely goes may result in reduced exposure to ETS, compared with unrestricted smoking.. asthma| child| cotinine| family relations| tobacco smoke pollution| smoking|environmental tobacco-smoke| parental smoking| passive smoking| exposure| household.	OCT-2000	asthma| child| cotinine| family relations| tobacco smoke pollution| smoking|environmental tobacco-smoke| parental smoking| passive smoking| exposure| household	Wakefield, M; Banham, D; Martin, J; Ruffin, R; McCaul, K; Badcock, N	Restrictions on smoking at home and urinary cotinine levels among children with asthma		AMERICAN JOURNAL OF PREVENTIVE MEDICINE	asthma; child; cotinine; family relations; tobacco smoke pollution; smoking	ENVIRONMENTAL TOBACCO-SMOKE; PARENTAL SMOKING; PASSIVE SMOKING; EXPOSURE; HOUSEHOLD	Objectives: The purpose of this study was to determine the extent to which various levels of restrictions on smoking in the home may be associated with children's exposure to environmental tobacco smoke (ETS). Methods: The methodology consisted of a cross-sectional survey involving 249 children with asthma aged 1 to 11 attending hospital outpatient clinics, with at least one parent who smoked, linked to the child's urinary cotinine to creatinine rations (CCR). Results: After adjustment for child's age, mother's smoking status, and total parental daily cigarette consumption, a total ban was associated with significantly lower urinary CCR levels (7.6 nmol/mmol) than bans with exceptions or limited smoking in the home. Where exceptions to bans were made (14.9 nmol/mmol), children's urinary CCR levels were no different from homes in which smoking was allowed in rooms the child rarely frequented (14.1 nmol/mmol). These two intermediate levels of restriction were in turn associated with significantly lower CCR levels than unrestricted smoking in the home (26.0 nmol/mmol). Conclusions: Making exceptions to bans on smoking at home measurably undermines the protective effect of a ban. However, making some exceptions to a ban and limiting smoking to rooms where the child rarely goes may result in reduced exposure to ETS, compared with unrestricted smoking.	28	88	2000	5	10.1016/S0749-3797(00)00197-5	Public, Environmental & Occupational Health; General & Internal Medicine
Childhood exposure to infection and risk of adult onset wheeze and atopy. Background-The prevalence of asthma and allergic diseases in children and young adults is inversely associated with family size. It has been suggested that more frequent exposure to infections in a large family group, particularly those spread by the faecal-oral route, may protect against atopic diseases, although not all published data support this hypothesis. Whether similar considerations apply to adult onset wheeze is unknown. The relationship between adult onset wheezing and atopy measured in adulthood and childhood exposure to a range of infections was investigated. Methods-A nested case control study of participants in a 30 year follow up survey was conducted. Questionnaire data on childhood infections had been obtained in a 1964 survey. In 1995 a further questionnaire on respiratory symptoms and other risk factors for wheezing illness was administered, total IgE, skin and RAST tests were performed, and serum was stored. In 1999 serological tests for hepatitis A, Helicobacter pylori, and Toxoplasma gondii were performed on the stored samples. Information from the 1964 questionnaires was available for 97 cases and 208 controls and serological tests were obtained for 85 cases and 190 controls. The potential risk factors were examined for all cases, those who reported doctor diagnosed asthma, those who described persistent cough and phlegm with wheeze, and subjects stratified by atopic status. Results-The sibship structure was similar in cases and controls. In univariate analysis of all cases, childhood infections reported by parents as acquired either before or after the age of three years did not influence case:control or atopic status. Seropositivity was also similar for all cases and controls, but cases in the subgroup with chronic cough and phlegm were more likely to be seropositive for hepatitis A and H pylori. Seropositivity was unrelated to atopic status. In multivariate analyses both the effect of having two or more younger siblings (OR 0.1, 95% CI 0.03 to 0.8) and of acquiring measles up to the age of three (OR 0.2, CI 0.03 to 0.8) were significantly related to a lower risk of doctor diagnosed asthma. Conclusions-In these well characterised subjects, exposure to infections as measured by parental reports obtained at age 10-14 years and by serological tests obtained in adulthood did not influence the development of wheezing symptoms or atopic status in adulthood. However, early exposure to measles and family size may be associated with a lower risk of adult onset doctor diagnosed asthma.. childhood infections| family size| adult onset wheeze| asthma| atopy|family-size| hay-fever| prevalence| association| symptoms| children| asthma.	MAY-2000	childhood infections| family size| adult onset wheeze| asthma| atopy|family-size| hay-fever| prevalence| association| symptoms| children| asthma	Bodner, C; Anderson, WJ; Reid, TS; Godden, DJ	Childhood exposure to infection and risk of adult onset wheeze and atopy		THORAX	childhood infections; family size; adult onset wheeze; asthma; atopy	FAMILY-SIZE; HAY-FEVER; PREVALENCE; ASSOCIATION; SYMPTOMS; CHILDREN; ASTHMA	Background-The prevalence of asthma and allergic diseases in children and young adults is inversely associated with family size. It has been suggested that more frequent exposure to infections in a large family group, particularly those spread by the faecal-oral route, may protect against atopic diseases, although not all published data support this hypothesis. Whether similar considerations apply to adult onset wheeze is unknown. The relationship between adult onset wheezing and atopy measured in adulthood and childhood exposure to a range of infections was investigated. Methods-A nested case control study of participants in a 30 year follow up survey was conducted. Questionnaire data on childhood infections had been obtained in a 1964 survey. In 1995 a further questionnaire on respiratory symptoms and other risk factors for wheezing illness was administered, total IgE, skin and RAST tests were performed, and serum was stored. In 1999 serological tests for hepatitis A, Helicobacter pylori, and Toxoplasma gondii were performed on the stored samples. Information from the 1964 questionnaires was available for 97 cases and 208 controls and serological tests were obtained for 85 cases and 190 controls. The potential risk factors were examined for all cases, those who reported doctor diagnosed asthma, those who described persistent cough and phlegm with wheeze, and subjects stratified by atopic status. Results-The sibship structure was similar in cases and controls. In univariate analysis of all cases, childhood infections reported by parents as acquired either before or after the age of three years did not influence case:control or atopic status. Seropositivity was also similar for all cases and controls, but cases in the subgroup with chronic cough and phlegm were more likely to be seropositive for hepatitis A and H pylori. Seropositivity was unrelated to atopic status. In multivariate analyses both the effect of having two or more younger siblings (OR 0.1, 95% CI 0.03 to 0.8) and of acquiring measles up to the age of three (OR 0.2, CI 0.03 to 0.8) were significantly related to a lower risk of doctor diagnosed asthma. Conclusions-In these well characterised subjects, exposure to infections as measured by parental reports obtained at age 10-14 years and by serological tests obtained in adulthood did not influence the development of wheezing symptoms or atopic status in adulthood. However, early exposure to measles and family size may be associated with a lower risk of adult onset doctor diagnosed asthma.	20	88	2000	5	10.1136/thorax.55.5.383	Respiratory System
Allergic Reactions to Foods in Preschool-Aged Children in a Prospective Observational Food Allergy Study. OBJECTIVE: To examine circumstances of allergic reactions to foods in a cohort of preschool-aged children. METHODS: We conducted a prospective, 5-site observational study of 512 infants aged 3 to 15 months with documented or likely allergy to milk or egg, and collected data prospectively examining allergic reactions. RESULTS: Over a median follow-up of 36 months (range: 0-48.4), the annualized reaction rate was 0.81 per year (367/512 subjects reporting 1171 reactions [95% confidence interval: 0.76-0.85]). Overall, 269/512 (52.5%) reported >1 reaction. The majority of reactions (71.2%) were triggered by milk (495 [42.3%]), egg (246 [21.0%]), and peanut (93 [7.9%]), with accidental exposures attributed to unintentional ingestion, label-reading errors, and cross-contact. Foods were provided by persons other than parents in 50.6% of reactions. Of 834 reactions to milk, egg, or peanut, 93 (11.2%) were attributed to purposeful exposures to these avoided foods. A higher number of food allergies (P < .0001) and higher food-specific immunoglobulin E (P < .0001) were associated with reactions. Of the 11.4% of reactions (n = 134) that were severe, 29.9% were treated with epinephrine. Factors resulting in undertreatment included lack of recognition of severity, epinephrine being unavailable, and fears about epinephrine administration. CONCLUSIONS: There was a high frequency of reactions caused by accidental and nonaccidental exposures. Undertreatment of severe reactions with epinephrine was a substantial problem. Areas for improved education include the need for constant vigilance, accurate label reading, avoidance of nonaccidental exposure, prevention of cross-contamination, appropriate epinephrine administration, and education of all caretakers. Pediatrics 2012;130:e25-e32. food allergy| ige-mediated allergic reaction| epinephrine|tree-nut-allergy| peanut allergy| united-states| epinephrine| ige| anaphylaxis| challenges| prevalence| features| registry.	JUL-2012	food allergy| ige-mediated allergic reaction| epinephrine|tree-nut-allergy| peanut allergy| united-states| epinephrine| ige| anaphylaxis| challenges| prevalence| features| registry	Fleischer, DM; Perry, TT; Atkins, D; Wood, RA; Burks, AW; Jones, SM; Henning, AK; Stablein, D; Sampson, HA; Sicherer, SH	Allergic Reactions to Foods in Preschool-Aged Children in a Prospective Observational Food Allergy Study		PEDIATRICS	food allergy; IgE-mediated allergic reaction; epinephrine	TREE-NUT-ALLERGY; PEANUT ALLERGY; UNITED-STATES; EPINEPHRINE; IGE; ANAPHYLAXIS; CHALLENGES; PREVALENCE; FEATURES; REGISTRY	OBJECTIVE: To examine circumstances of allergic reactions to foods in a cohort of preschool-aged children. METHODS: We conducted a prospective, 5-site observational study of 512 infants aged 3 to 15 months with documented or likely allergy to milk or egg, and collected data prospectively examining allergic reactions. RESULTS: Over a median follow-up of 36 months (range: 0-48.4), the annualized reaction rate was 0.81 per year (367/512 subjects reporting 1171 reactions [95% confidence interval: 0.76-0.85]). Overall, 269/512 (52.5%) reported >1 reaction. The majority of reactions (71.2%) were triggered by milk (495 [42.3%]), egg (246 [21.0%]), and peanut (93 [7.9%]), with accidental exposures attributed to unintentional ingestion, label-reading errors, and cross-contact. Foods were provided by persons other than parents in 50.6% of reactions. Of 834 reactions to milk, egg, or peanut, 93 (11.2%) were attributed to purposeful exposures to these avoided foods. A higher number of food allergies (P < .0001) and higher food-specific immunoglobulin E (P < .0001) were associated with reactions. Of the 11.4% of reactions (n = 134) that were severe, 29.9% were treated with epinephrine. Factors resulting in undertreatment included lack of recognition of severity, epinephrine being unavailable, and fears about epinephrine administration. CONCLUSIONS: There was a high frequency of reactions caused by accidental and nonaccidental exposures. Undertreatment of severe reactions with epinephrine was a substantial problem. Areas for improved education include the need for constant vigilance, accurate label reading, avoidance of nonaccidental exposure, prevention of cross-contamination, appropriate epinephrine administration, and education of all caretakers. Pediatrics 2012;130:e25-e32	31	87	2012	8	10.1542/peds.2011-1762	Pediatrics
Sources of Bacteria in Outdoor Air across Cities in the Midwestern United States. Bacteria are abundant in the atmosphere, where they often represent a major portion of the organic aerosols. Potential pathogens of plants and livestock are commonly dispersed through the atmosphere, and airborne bacteria can have important effects on human health as pathogens or triggers of allergic asthma and seasonal allergies. Despite their importance, the diversity and biogeography of airborne microorganisms remain poorly understood. We used high-throughput pyrosequencing to analyze bacterial communities present in the aerosol fraction containing fine particulate matter of <= 2.5 mu m from 96 near-surface atmospheric samples collected from cities throughout the midwestern United States and found that the communities are surprisingly diverse and strongly affected by the season. We also directly compared the airborne communities to those found in hundreds of samples representing potential source environments. We show that, in addition to the more predictable sources (soils and leaf surfaces), fecal material, most likely dog feces, often represents an unexpected source of bacteria in the atmosphere at more urbanized locations during the winter. Airborne bacteria are clearly an important, but understudied, component of air quality that needs to be better integrated into efforts to measure and model pollutants in the atmosphere.. ribosomal-rna gene| microbial communities| biological particles| airborne bacterial| diversity| sequences| atmosphere| ecology| biodiversity| variability.	SEP-2011	ribosomal-rna gene| microbial communities| biological particles| airborne bacterial| diversity| sequences| atmosphere| ecology| biodiversity| variability	Bowers, RM; Sullivan, AP; Costello, EK; Collett, JL; Knight, R; Fierer, N	Sources of Bacteria in Outdoor Air across Cities in the Midwestern United States		APPLIED AND ENVIRONMENTAL MICROBIOLOGY		RIBOSOMAL-RNA GENE; MICROBIAL COMMUNITIES; BIOLOGICAL PARTICLES; AIRBORNE BACTERIAL; DIVERSITY; SEQUENCES; ATMOSPHERE; ECOLOGY; BIODIVERSITY; VARIABILITY	Bacteria are abundant in the atmosphere, where they often represent a major portion of the organic aerosols. Potential pathogens of plants and livestock are commonly dispersed through the atmosphere, and airborne bacteria can have important effects on human health as pathogens or triggers of allergic asthma and seasonal allergies. Despite their importance, the diversity and biogeography of airborne microorganisms remain poorly understood. We used high-throughput pyrosequencing to analyze bacterial communities present in the aerosol fraction containing fine particulate matter of <= 2.5 mu m from 96 near-surface atmospheric samples collected from cities throughout the midwestern United States and found that the communities are surprisingly diverse and strongly affected by the season. We also directly compared the airborne communities to those found in hundreds of samples representing potential source environments. We show that, in addition to the more predictable sources (soils and leaf surfaces), fecal material, most likely dog feces, often represents an unexpected source of bacteria in the atmosphere at more urbanized locations during the winter. Airborne bacteria are clearly an important, but understudied, component of air quality that needs to be better integrated into efforts to measure and model pollutants in the atmosphere.	47	87	2011	7	10.1128/AEM.05498-11	Biotechnology & Applied Microbiology; Microbiology
Associations between Fungal Species and Water-Damaged Building Materials. Fungal growth in damp or water-damaged buildings worldwide is an increasing problem, which has adverse effects on both the occupants and the buildings. Air sampling alone in moldy buildings does not reveal the full diversity of fungal species growing on building materials. One aim of this study was to estimate the qualitative and quantitative diversity of fungi growing on damp or water-damaged building materials. Another was to determine if associations exist between the most commonly found fungal species and different types of materials. More than 5,300 surface samples were taken by means of V8 contact plates from materials with visible fungal growth. Fungal identifications and information on building material components were analyzed using multivariate statistic methods to determine associations between fungi and material components. The results confirmed that Penicillium chrysogenum and Aspergillus versicolor are the most common fungal species in water-damaged buildings. The results also showed Chaetomium spp., Acremonium spp., and Ulocladium spp. to be very common on damp building materials. Analyses show that associated mycobiotas exist on different building materials. Associations were found between (i) Acremonium spp., Penicillium chrysogenum, Stachybotrys spp., Ulocladium spp., and gypsum and wallpaper, (ii) Arthrinium phaeospermum, Aureobasidium pullulans, Cladosporium herbarum, Trichoderma spp., yeasts, and different types of wood and plywood, and (iii) Aspergillus fumigatus, Aspergillus melleus, Aspergillus niger, Aspergillus ochraceus, Chaetomium spp., Mucor racemosus, Mucor spinosus, and concrete and other floor-related materials. These results can be used to develop new and resistant building materials and relevant allergen extracts and to help focus research on relevant mycotoxins, microbial volatile organic compounds (MVOCs), and microparticles released into the indoor environment.. danish homes| residential characteristics| stachybotrys-chartarum| moldy homes| micro-fungi| house dust| indoor air| airborne| moisture| identification.	JUN-2011	danish homes| residential characteristics| stachybotrys-chartarum| moldy homes| micro-fungi| house dust| indoor air| airborne| moisture| identification	Andersen, B; Frisvad, JC; Sondergaard, I; Rasmussen, IS; Larsen, LS	Associations between Fungal Species and Water-Damaged Building Materials		APPLIED AND ENVIRONMENTAL MICROBIOLOGY		DANISH HOMES; RESIDENTIAL CHARACTERISTICS; STACHYBOTRYS-CHARTARUM; MOLDY HOMES; MICRO-FUNGI; HOUSE DUST; INDOOR AIR; AIRBORNE; MOISTURE; IDENTIFICATION	Fungal growth in damp or water-damaged buildings worldwide is an increasing problem, which has adverse effects on both the occupants and the buildings. Air sampling alone in moldy buildings does not reveal the full diversity of fungal species growing on building materials. One aim of this study was to estimate the qualitative and quantitative diversity of fungi growing on damp or water-damaged building materials. Another was to determine if associations exist between the most commonly found fungal species and different types of materials. More than 5,300 surface samples were taken by means of V8 contact plates from materials with visible fungal growth. Fungal identifications and information on building material components were analyzed using multivariate statistic methods to determine associations between fungi and material components. The results confirmed that Penicillium chrysogenum and Aspergillus versicolor are the most common fungal species in water-damaged buildings. The results also showed Chaetomium spp., Acremonium spp., and Ulocladium spp. to be very common on damp building materials. Analyses show that associated mycobiotas exist on different building materials. Associations were found between (i) Acremonium spp., Penicillium chrysogenum, Stachybotrys spp., Ulocladium spp., and gypsum and wallpaper, (ii) Arthrinium phaeospermum, Aureobasidium pullulans, Cladosporium herbarum, Trichoderma spp., yeasts, and different types of wood and plywood, and (iii) Aspergillus fumigatus, Aspergillus melleus, Aspergillus niger, Aspergillus ochraceus, Chaetomium spp., Mucor racemosus, Mucor spinosus, and concrete and other floor-related materials. These results can be used to develop new and resistant building materials and relevant allergen extracts and to help focus research on relevant mycotoxins, microbial volatile organic compounds (MVOCs), and microparticles released into the indoor environment.	53	87	2011	9	10.1128/AEM.02513-10	Biotechnology & Applied Microbiology; Microbiology
"Aetiology of childhood leukaemia. The acute leukaemias account for about 30% of all malignancy seen in childhood across the Western world. A peak incidence of precursor B cell ALL has emerged as socio-economic conditions have improved in countries worldwide. From twin studies and the use of neonatal blood spots it has been possible to back track the first initiating genetic events within critical haemopoietic cells to foetal development in utero for most precursor B cell ALL and some cases of AML These events may occur as part of normal foetal development. Whether other factors (environmental or constitutional) are involved to increase the chance of these first genetic changes happening is unclear. For some leukaemias (e.g. infant MLL positive ALL) the first event appears adequate to create a malignant clone but for the majority of ALL and AML further 'genetic' changes are required, probably postnatal. Many environmental factors have been proposed as causative for leukaemia but only ionising irradiation and certain chemicals, e.g. benzene and cytotoxics (alkylators and topoisomerase II inhibitors) have been confirmed and then principally for acute myeloid leukaemia. It appears increasingly likely that delayed. dysregulated responses to 'common' infectious agents play a major part in the conversion of pre-leukaemic clones into overt precursor B cell ALL the most common form of childhood leukaemia. Constitutional polymorphic alleleic variants in immune response genes (especially the HLA Class II proteins) and cytokines may play a role in determining the type of immune response. High penetrance germ-line mutations are involved in only about 5% of childhood leukaemias (more in AML than ALL). There is little evidence to support any role of viral transformation in causation, unlike in animals. Other environmental factors for which some evidence exists include non-ionising electromagnetic radiation and electric fields, although their mode of action in leukaemogenesis remains unclear. There is no single cause for childhood leukaemia and for most individuals a combination of factors appears to be necessary; all involving gene-environment interactions. To date few clear preventative measures have emerged, except the complete avoidance of first trimester X-rays in pregnancy; a healthy diet with adequate oral folic acid intake both preconception and early in pregnancy; and the early exposure of children to other children outside the home to facilitate stimulation and maturation of the natural immune system. Here then are clear echoes of the ""hygiene hypothesis"" regarding the initiation of allergies, autoimmune disease and type I diabetes mellitus in children and young people. (C) 2010 Published by Elsevier Ltd.. aetiology| childhood leukaemia|acute lymphoblastic-leukemia| childrens-cancer-group| non-hodgkins-lymphoma| day-care attendance| parental alcohol-consumption| acute lymphocytic-leukemia| acute myeloid-leukemia| voltage power-lines| vitamin-k| ionizing-radiation."	JUN-2010	aetiology| childhood leukaemia|acute lymphoblastic-leukemia| childrens-cancer-group| non-hodgkins-lymphoma| day-care attendance| parental alcohol-consumption| acute lymphocytic-leukemia| acute myeloid-leukemia| voltage power-lines| vitamin-k| ionizing-radiation	Eden, T	Aetiology of childhood leukaemia		CANCER TREATMENT REVIEWS	Aetiology; Childhood leukaemia	ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDRENS-CANCER-GROUP; NON-HODGKINS-LYMPHOMA; DAY-CARE ATTENDANCE; PARENTAL ALCOHOL-CONSUMPTION; ACUTE LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; VOLTAGE POWER-LINES; VITAMIN-K; IONIZING-RADIATION	"The acute leukaemias account for about 30% of all malignancy seen in childhood across the Western world. A peak incidence of precursor B cell ALL has emerged as socio-economic conditions have improved in countries worldwide. From twin studies and the use of neonatal blood spots it has been possible to back track the first initiating genetic events within critical haemopoietic cells to foetal development in utero for most precursor B cell ALL and some cases of AML These events may occur as part of normal foetal development. Whether other factors (environmental or constitutional) are involved to increase the chance of these first genetic changes happening is unclear. For some leukaemias (e.g. infant MLL positive ALL) the first event appears adequate to create a malignant clone but for the majority of ALL and AML further 'genetic' changes are required, probably postnatal. Many environmental factors have been proposed as causative for leukaemia but only ionising irradiation and certain chemicals, e.g. benzene and cytotoxics (alkylators and topoisomerase II inhibitors) have been confirmed and then principally for acute myeloid leukaemia. It appears increasingly likely that delayed. dysregulated responses to 'common' infectious agents play a major part in the conversion of pre-leukaemic clones into overt precursor B cell ALL the most common form of childhood leukaemia. Constitutional polymorphic alleleic variants in immune response genes (especially the HLA Class II proteins) and cytokines may play a role in determining the type of immune response. High penetrance germ-line mutations are involved in only about 5% of childhood leukaemias (more in AML than ALL). There is little evidence to support any role of viral transformation in causation, unlike in animals. Other environmental factors for which some evidence exists include non-ionising electromagnetic radiation and electric fields, although their mode of action in leukaemogenesis remains unclear. There is no single cause for childhood leukaemia and for most individuals a combination of factors appears to be necessary; all involving gene-environment interactions. To date few clear preventative measures have emerged, except the complete avoidance of first trimester X-rays in pregnancy; a healthy diet with adequate oral folic acid intake both preconception and early in pregnancy; and the early exposure of children to other children outside the home to facilitate stimulation and maturation of the natural immune system. Here then are clear echoes of the ""hygiene hypothesis"" regarding the initiation of allergies, autoimmune disease and type I diabetes mellitus in children and young people. (C) 2010 Published by Elsevier Ltd."	142	87	2010	12	10.1016/j.ctrv.2010.02.004	Oncology
Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Background In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. Objectives To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). Methods In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n = 16), SCIT (n = 16) or pharmacotherapy alone (n = 16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-gamma, IL-10, and TGF-beta secretions were measured. Results SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (P<0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-beta (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines. Conclusion Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.. asthma| cytokines| nasal provocation| rhinitis| sublingual-subcutaneous immunotherapy|grass-pollen immunotherapy| allergen-specific immunotherapy| t-regulatory cells| double-blind| pediatric-patients| double-dummy| asthma| rhinitis| childhood| metaanalysis.	JUN-2010	asthma| cytokines| nasal provocation| rhinitis| sublingual-subcutaneous immunotherapy|grass-pollen immunotherapy| allergen-specific immunotherapy| t-regulatory cells| double-blind| pediatric-patients| double-dummy| asthma| rhinitis| childhood| metaanalysis	Eifan, AO; Akkoc, T; Yildiz, A; Keles, S; Ozdemir, C; Bahceciler, NN; Barlan, IB	Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; cytokines; nasal provocation; rhinitis; sublingual-subcutaneous immunotherapy	GRASS-POLLEN IMMUNOTHERAPY; ALLERGEN-SPECIFIC IMMUNOTHERAPY; T-REGULATORY CELLS; DOUBLE-BLIND; PEDIATRIC-PATIENTS; DOUBLE-DUMMY; ASTHMA; RHINITIS; CHILDHOOD; METAANALYSIS	Background In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. Objectives To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). Methods In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n = 16), SCIT (n = 16) or pharmacotherapy alone (n = 16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-gamma, IL-10, and TGF-beta secretions were measured. Results SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (P<0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-beta (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines. Conclusion Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.	36	87	2010	11	10.1111/j.1365-2222.2009.03448.x	Allergy; Immunology
Increased risk of serious pneumococcal disease in patients with asthma. Background: Individuals with asthma have been reported to be at increased risk of invasive pneumococcal disease (IPD). These findings need to be confirmed in a different population-based study setting. Objective: We assessed whether serious pneumococcal disease (SPD), defined as an IPD, pneumococcal pneumonia, or both, was associated with asthma status. Methods: This is a retrospective case-control study using criteria-based methods for ascertaining SPD, as well as asthma. Subjects were residents of Rochester, Minnesota, who had SPD between 1964 and 1983 (the primarily pre-pneumococcal vaccine era) and their age-and sex-matched control subjects using 1:2 matching. Potential cases and control subjects were identified by using the Rochester Epidemiology project database and confirmed by medical record reviews. All cases and control subjects were merged with the database comprising the entire pool of Rochester residents with and without asthma between 1964 and 1983. Results: A total of 3941 records of potential patients with SPD were reviewed, and we identified 174 cases of SPD (51% male subjects and 94% white subjects). SPD was associated with a history of asthma among all ages (odds ratio, 2.4; 95% CI, 0.96.6; P = .09) and among adults (odds ratio, 6.7; 95% CI, 1.627.3; P = .01), controlling for high-risk conditions for IPD and smoking exposure. The population-attributable risk percentage was 17% in the adult population. Conclusion: Adults with asthma might be at increased risk of SPD.. asthma| invasive pneumococcal disease| epidemiology| risk| microbial infection| pneumococcal pneumonia| adults| rochester epidemiology project|immune-response| vaccine| epidemiology| community| mice| infections| pneumoniae| childhood| clearance| symptoms.	OCT-2008	asthma| invasive pneumococcal disease| epidemiology| risk| microbial infection| pneumococcal pneumonia| adults| rochester epidemiology project|immune-response| vaccine| epidemiology| community| mice| infections| pneumoniae| childhood| clearance| symptoms	Juhn, YJ; Kita, H; Yawn, BP; Boyce, TG; Yoo, KH; McGree, ME; Weaver, AL; Wollan, P; Jacobson, RM	Increased risk of serious pneumococcal disease in patients with asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; invasive pneumococcal disease; epidemiology; risk; microbial infection; pneumococcal pneumonia; adults; Rochester Epidemiology Project	IMMUNE-RESPONSE; VACCINE; EPIDEMIOLOGY; COMMUNITY; MICE; INFECTIONS; PNEUMONIAE; CHILDHOOD; CLEARANCE; SYMPTOMS	Background: Individuals with asthma have been reported to be at increased risk of invasive pneumococcal disease (IPD). These findings need to be confirmed in a different population-based study setting. Objective: We assessed whether serious pneumococcal disease (SPD), defined as an IPD, pneumococcal pneumonia, or both, was associated with asthma status. Methods: This is a retrospective case-control study using criteria-based methods for ascertaining SPD, as well as asthma. Subjects were residents of Rochester, Minnesota, who had SPD between 1964 and 1983 (the primarily pre-pneumococcal vaccine era) and their age-and sex-matched control subjects using 1:2 matching. Potential cases and control subjects were identified by using the Rochester Epidemiology project database and confirmed by medical record reviews. All cases and control subjects were merged with the database comprising the entire pool of Rochester residents with and without asthma between 1964 and 1983. Results: A total of 3941 records of potential patients with SPD were reviewed, and we identified 174 cases of SPD (51% male subjects and 94% white subjects). SPD was associated with a history of asthma among all ages (odds ratio, 2.4; 95% CI, 0.96.6; P = .09) and among adults (odds ratio, 6.7; 95% CI, 1.627.3; P = .01), controlling for high-risk conditions for IPD and smoking exposure. The population-attributable risk percentage was 17% in the adult population. Conclusion: Adults with asthma might be at increased risk of SPD.	31	87	2008	5	10.1016/j.jaci.2008.07.029	Allergy; Immunology
Important research questions in allergy and related diseases: nonallergic rhinitis: a GA(2)LEN paper. Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE-dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co-morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto-immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis.. asthma| epidemiology| ga(2)len| inflammation| nonallergic| rhinitis|noninfectious perennial rhinitis| respiratory-health-survey| quality-of-life| independent risk-factor| european birth cohort| local ige production| skin-test reactivity| nasal-mucosa| air-pollution| eosinophil apoptosis.	JUL-2008	asthma| epidemiology| ga(2)len| inflammation| nonallergic| rhinitis|noninfectious perennial rhinitis| respiratory-health-survey| quality-of-life| independent risk-factor| european birth cohort| local ige production| skin-test reactivity| nasal-mucosa| air-pollution| eosinophil apoptosis	Bousquet, J; Fokkens, W; Burney, P; Durham, SR; Bachert, C; Akdis, CA; Canonica, GW; Dahlen, SE; Zuberbier, T; Bieber, T; Bonini, S; Bousquet, PJ; Brozek, JL; Cardell, LO; Crameri, R; Custovic, A; Demoly, P; van Wijk, RG; Gjomarkaj, M; Holland, C; Howarth, P; Humbert, M; Johnston, SL; Kauffmann, F; Kowalski, ML; Lambrecht, B; Lehmann, S; Leynaert, B; Lodrup-Carlsen, K; Mullol, J; Niggemann, B; Nizankowska-Mogilnicka, E; Papadopoulos, N; Passalacqua, G; Schunemann, HJ; Simon, HU; Todo-Bom, A; Toskala, E; Valenta, R; Wickman, M; Zock, JP	Important research questions in allergy and related diseases: nonallergic rhinitis: a GA(2)LEN paper		ALLERGY	asthma; epidemiology; GA(2)LEN; inflammation; nonallergic; rhinitis	NONINFECTIOUS PERENNIAL RHINITIS; RESPIRATORY-HEALTH-SURVEY; QUALITY-OF-LIFE; INDEPENDENT RISK-FACTOR; EUROPEAN BIRTH COHORT; LOCAL IGE PRODUCTION; SKIN-TEST REACTIVITY; NASAL-MUCOSA; AIR-POLLUTION; EOSINOPHIL APOPTOSIS	Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE-dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co-morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto-immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis.	154	87	2008	12	10.1111/j.1398-9995.2008.01715.x	Allergy; Immunology
Toll-like receptor heterodimer variants protect from childhood asthma. Background: Early exposure to microbes reduces the risk for asthma. Toll-like receptors (TLRs) represent a major group of receptors for the specific recognition of pathogen-associated molecular patterns of microbes capable of activating innate and adaptive immunity. Objective: Because TLRs can influence key events in the induction and perpetuation of asthma and atopy, we sought to determine whether genetic alterations in TLR genes affect asthma risk. Methods: We systematically evaluated putatively functional genetic variants in all 10 human TLR genes for their association with different asthma phenotypes in a case-control study (n = 1872) by using matrix-assisted laser desorption/ionization time-of-flight genotyping. For polymorphisms showing association with atopic asthma, effects on gene and protein expression were studied by means of RT-PCR and flow cytometry ex vivo. T-cell cytokine production was evaluated by means of ELISA after stimulation of the respective TLRs with specific ligands. Results: Protective effects on atopic asthma were identified for single nucleotide polymorphisms in TLR1 (odds ratio [OR], 0.54; 95% CI, 0.37-0.81; P =.002), TLR6 (OR, 0.54; 95% CI, 0.37-0.79; P =.003), and TLR10 (OR, 0.58; 95% CI, 0.39-0.86; P =.006), all capable of forming heterodimers with TLR2. Effects remained significant after correction for multiple comparisons. PBMCs of minor allele carriers showed increased levels of the respective TLR mRNA and proteins, augmented inflammatory responses, increased T(H)1 cytokine expression, and reduced T(H)2-associated IL-4 production after specific stimulation. Conclusion: These results suggest that functional relevant TLR1 and TLR6 variants are directly involved in asthma development.. asthma| atopic asthma| toll-like receptor| heterodimer| polymorphism|hay-fever| children| cells| atopy| polymorphisms| population| prevalence| mechanisms| expression| haplotypes.	JUL-2008	asthma| atopic asthma| toll-like receptor| heterodimer| polymorphism|hay-fever| children| cells| atopy| polymorphisms| population| prevalence| mechanisms| expression| haplotypes	Kormann, MSD; Depner, M; Harti, D; Klopp, N; Illig, T; Adamski, J; Vogelberg, C; Weiland, SK; von Mutius, E; Kabesch, M	Toll-like receptor heterodimer variants protect from childhood asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	asthma; atopic asthma; toll-like receptor; heterodimer; polymorphism	HAY-FEVER; CHILDREN; CELLS; ATOPY; POLYMORPHISMS; POPULATION; PREVALENCE; MECHANISMS; EXPRESSION; HAPLOTYPES	Background: Early exposure to microbes reduces the risk for asthma. Toll-like receptors (TLRs) represent a major group of receptors for the specific recognition of pathogen-associated molecular patterns of microbes capable of activating innate and adaptive immunity. Objective: Because TLRs can influence key events in the induction and perpetuation of asthma and atopy, we sought to determine whether genetic alterations in TLR genes affect asthma risk. Methods: We systematically evaluated putatively functional genetic variants in all 10 human TLR genes for their association with different asthma phenotypes in a case-control study (n = 1872) by using matrix-assisted laser desorption/ionization time-of-flight genotyping. For polymorphisms showing association with atopic asthma, effects on gene and protein expression were studied by means of RT-PCR and flow cytometry ex vivo. T-cell cytokine production was evaluated by means of ELISA after stimulation of the respective TLRs with specific ligands. Results: Protective effects on atopic asthma were identified for single nucleotide polymorphisms in TLR1 (odds ratio [OR], 0.54; 95% CI, 0.37-0.81; P =.002), TLR6 (OR, 0.54; 95% CI, 0.37-0.79; P =.003), and TLR10 (OR, 0.58; 95% CI, 0.39-0.86; P =.006), all capable of forming heterodimers with TLR2. Effects remained significant after correction for multiple comparisons. PBMCs of minor allele carriers showed increased levels of the respective TLR mRNA and proteins, augmented inflammatory responses, increased T(H)1 cytokine expression, and reduced T(H)2-associated IL-4 production after specific stimulation. Conclusion: These results suggest that functional relevant TLR1 and TLR6 variants are directly involved in asthma development.	29	87	2008	7	10.1016/j.jaci.2008.04.039	Allergy; Immunology
Food allergy and the introduction of solid foods to infants: a consensus document. Objective: To make recommendations based on a critical review of the evidence for the timing of the introduction of solid foods and its possible role in the development of food allergy. Data Sources: MEDLINE searches using the following search algorithm: [weaning AND infant AND allergy]/[food allergy AND sensitization]/[dietary prevention AND food allergy OR allergens]/[Jan 1980-Feb 2006]. Study Selection: Using the authors' clinical experience and research expertise, 52 studies were retrieved that satisfied the following conditions: English language, journal impact factor above I or scientific society, expert, or institutional publication, and appraisable using the World Health Organization categories of evidence. Results: Available information suggests that early introduction can increase the risk of food allergy, that avoidance of solids can prevent the development of specific food allergies, that some foods are more allergenic than others, and that some food allergies are more persistent than others. Conclusions: Pediatricians and allergists should cautiously individualize the introduction of solids into the infants' diet. With assessed risk of allergy, the optimal age for the introduction of selected supplemental foods should be 6 months, dairy products 12 months, hen's egg 24 months, and peanut, tree nuts, fish, and seafood at least 36 months. For all infants, complementary feeding can be introduced from the sixth month, and egg, peanut, tree nuts, fish, and seafood introduction require caution. Foods should be introduced one at a time in small amounts. Mixed foods containing various food allergens should not be given unless tolerance to every ingredient has been assessed.. bovine serum-albumin| breast-fed infants| cows milk allergy| high-risk infants| partial whey hydrolysate| house-dust-mite| peanut allergy| natural-history| atopic disease| cross-reactivity.	JUL-2006	bovine serum-albumin| breast-fed infants| cows milk allergy| high-risk infants| partial whey hydrolysate| house-dust-mite| peanut allergy| natural-history| atopic disease| cross-reactivity	Fiocchi, A; Assa'ad, A; Bahna, S	Food allergy and the introduction of solid foods to infants: a consensus document		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		BOVINE SERUM-ALBUMIN; BREAST-FED INFANTS; COWS MILK ALLERGY; HIGH-RISK INFANTS; PARTIAL WHEY HYDROLYSATE; HOUSE-DUST-MITE; PEANUT ALLERGY; NATURAL-HISTORY; ATOPIC DISEASE; CROSS-REACTIVITY	Objective: To make recommendations based on a critical review of the evidence for the timing of the introduction of solid foods and its possible role in the development of food allergy. Data Sources: MEDLINE searches using the following search algorithm: [weaning AND infant AND allergy]/[food allergy AND sensitization]/[dietary prevention AND food allergy OR allergens]/[Jan 1980-Feb 2006]. Study Selection: Using the authors' clinical experience and research expertise, 52 studies were retrieved that satisfied the following conditions: English language, journal impact factor above I or scientific society, expert, or institutional publication, and appraisable using the World Health Organization categories of evidence. Results: Available information suggests that early introduction can increase the risk of food allergy, that avoidance of solids can prevent the development of specific food allergies, that some foods are more allergenic than others, and that some food allergies are more persistent than others. Conclusions: Pediatricians and allergists should cautiously individualize the introduction of solids into the infants' diet. With assessed risk of allergy, the optimal age for the introduction of selected supplemental foods should be 6 months, dairy products 12 months, hen's egg 24 months, and peanut, tree nuts, fish, and seafood at least 36 months. For all infants, complementary feeding can be introduced from the sixth month, and egg, peanut, tree nuts, fish, and seafood introduction require caution. Foods should be introduced one at a time in small amounts. Mixed foods containing various food allergens should not be given unless tolerance to every ingredient has been assessed.	155	87	2006	11		Allergy; Immunology
Ragweed (Ambrosia) progression and its health risks: will Switzerland resist this invasion?. The purpose of this article is to alert physicians for the environmental and health threats of Ambrosia artemisiifolia (common ragweed) in Switzerland. Switzerland borders several heavily ragweed colonised areas. Up to 12% of the population suffers from allergies (hay fever, asthma) to ragweed pollen in these areas. Switzerland is beginning to be invaded by this plant. Currently, the ragweed pollen counts are still low but can reach local peaks that induce symptoms in allergic individuals. Ragweed allergy, however, is still rare in Switzerland. Because the amount of ragweed pollen was increasing in the last few years, identification and surveillance of ragweed plant foci was started. Colonisation is currently systematically monitored in Geneva and southern Tessin. Major accumulation of ragweed foci have been detected in the canton of Geneva, the western shore of the lake of Geneva belonging to the canton of Vaud, and in the southern part of the canton of Tessin, aside from minor foci registered all over Switzerland. The routes of ragweed invasion are presented and discussed. Current measures of ragweed containment and needs for the future are presented. The urge for these measures at an early stage of ragweed spread is underlined by the impracticability of eradication in highly colonised areas. The costs of preventing ragweed spread in Switzerland are likely to be several magnitudes lower than the treatment of a significant percentage of the Swiss population for ragweed pollen allergy. Because areas can change from low to heavy ragweed colonisation within a few years, the current window of opportunity to prevent further colonisation by ragweed should not be missed.. ambrosia| allergy| health risk| allergic rhinits| asthma| switzerland|allergic rhinitis| pollen allergy| hay-fever| late summer| immunotherapy| sensitization| efficacy| asthma| omalizumab| exposure.	SEP 17-2005	ambrosia| allergy| health risk| allergic rhinits| asthma| switzerland|allergic rhinitis| pollen allergy| hay-fever| late summer| immunotherapy| sensitization| efficacy| asthma| omalizumab| exposure	Taramarcaz, P; Lambelet, C; Clot, B; Keimer, C; Hauser, C	Ragweed (Ambrosia) progression and its health risks: will Switzerland resist this invasion?		SWISS MEDICAL WEEKLY	Ambrosia; allergy; health risk; allergic rhinits; asthma; Switzerland	ALLERGIC RHINITIS; POLLEN ALLERGY; HAY-FEVER; LATE SUMMER; IMMUNOTHERAPY; SENSITIZATION; EFFICACY; ASTHMA; OMALIZUMAB; EXPOSURE	The purpose of this article is to alert physicians for the environmental and health threats of Ambrosia artemisiifolia (common ragweed) in Switzerland. Switzerland borders several heavily ragweed colonised areas. Up to 12% of the population suffers from allergies (hay fever, asthma) to ragweed pollen in these areas. Switzerland is beginning to be invaded by this plant. Currently, the ragweed pollen counts are still low but can reach local peaks that induce symptoms in allergic individuals. Ragweed allergy, however, is still rare in Switzerland. Because the amount of ragweed pollen was increasing in the last few years, identification and surveillance of ragweed plant foci was started. Colonisation is currently systematically monitored in Geneva and southern Tessin. Major accumulation of ragweed foci have been detected in the canton of Geneva, the western shore of the lake of Geneva belonging to the canton of Vaud, and in the southern part of the canton of Tessin, aside from minor foci registered all over Switzerland. The routes of ragweed invasion are presented and discussed. Current measures of ragweed containment and needs for the future are presented. The urge for these measures at an early stage of ragweed spread is underlined by the impracticability of eradication in highly colonised areas. The costs of preventing ragweed spread in Switzerland are likely to be several magnitudes lower than the treatment of a significant percentage of the Swiss population for ragweed pollen allergy. Because areas can change from low to heavy ragweed colonisation within a few years, the current window of opportunity to prevent further colonisation by ragweed should not be missed.	90	87	2005	11		General & Internal Medicine
Computed tomographic imaging of the airways: relationship to structure and function. Alterations in the structure of the airways, collectively termed airway remodelling, contribute to airflow obstruction in a variety of chronic lung diseases. While histology has provided valuable insights into the structure of airway wall remodelling, this technique is invasive and does not allow the longitudinal analysis of airway wall dimensions. Technical advances in computed tomography allow the assessment of airway wall dimensions, and are ideally suited for the noninvasive investigation of the pathogenesis of airway wall remodelling and the evaluation of new therapeutic interventions. The aim of this article is to review the use of computed tomography in the investigation of airway structure and function in health and disease.. airways| asthma| chronic obstructive pulmonary disease| computed tomography| cystic fibrosis| lung structure and function|thin-section ct| high-resolution ct| obstructive pulmonary-disease| cystic-fibrosis lung| bronchial-wall thickness| placebo-controlled trial| atomic-bomb survivors| air-flow obstruction| young-children| asymptomatic subjects.	JUL-2005	airways| asthma| chronic obstructive pulmonary disease| computed tomography| cystic fibrosis| lung structure and function|thin-section ct| high-resolution ct| obstructive pulmonary-disease| cystic-fibrosis lung| bronchial-wall thickness| placebo-controlled trial| atomic-bomb survivors| air-flow obstruction| young-children| asymptomatic subjects	de Jong, PA; Muller, NL; Pare, PD; Coxson, HO	Computed tomographic imaging of the airways: relationship to structure and function		EUROPEAN RESPIRATORY JOURNAL	airways; asthma; chronic obstructive pulmonary disease; computed tomography; cystic fibrosis; lung structure and function	THIN-SECTION CT; HIGH-RESOLUTION CT; OBSTRUCTIVE PULMONARY-DISEASE; CYSTIC-FIBROSIS LUNG; BRONCHIAL-WALL THICKNESS; PLACEBO-CONTROLLED TRIAL; ATOMIC-BOMB SURVIVORS; AIR-FLOW OBSTRUCTION; YOUNG-CHILDREN; ASYMPTOMATIC SUBJECTS	Alterations in the structure of the airways, collectively termed airway remodelling, contribute to airflow obstruction in a variety of chronic lung diseases. While histology has provided valuable insights into the structure of airway wall remodelling, this technique is invasive and does not allow the longitudinal analysis of airway wall dimensions. Technical advances in computed tomography allow the assessment of airway wall dimensions, and are ideally suited for the noninvasive investigation of the pathogenesis of airway wall remodelling and the evaluation of new therapeutic interventions. The aim of this article is to review the use of computed tomography in the investigation of airway structure and function in health and disease.	166	87	2005	13	10.1183/09031936.05.00007105	Respiratory System
Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds. Aims: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. Methods: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. Results: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. Conclusions: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard.. respiratory sensitization| substances| identification| allergens| toxicity| exposure| disease.	APR-2005	respiratory sensitization| substances| identification| allergens| toxicity| exposure| disease	Jarvis, J; Seed, MJ; Elton, RA; Sawyer, L; Agius, RM	Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds		OCCUPATIONAL AND ENVIRONMENTAL MEDICINE		RESPIRATORY SENSITIZATION; SUBSTANCES; IDENTIFICATION; ALLERGENS; TOXICITY; EXPOSURE; DISEASE	Aims: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. Methods: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. Results: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. Conclusions: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard.	31	87	2005	8	10.1136/oem.2004.016402	Public, Environmental & Occupational Health
Violence exposure and traumatic stress symptoms as additional predictors of health problems in high-risk children. Objective To test the hypotheses that both violence and traumatic stress symptoms are associated with negative health status among poor preschool children. Study design This cross-sectional analysis of a Head Start preschool age cohort (n = 160) studied health outcomes parallel to those assessed in the 2001 National Health Interview Survey of child health (asthma, allergy, attention deficit hyperactivity disorder, global appraisal) its well as two stress-related somatic complaints, gastrointestinal problems and headache. Risk factors include sociodemographics, mothers' health factors, extent of exposure to violence and maltreatment, and mother- and teacher-reported traumatic stress symptoms. Results Compared with poor children in the National Health Interview Survey and their Head Start peers, children exposed to violence and those with high levels of traumatic stress had significantly, worse outcomes, in a dose-response relation. Being abused, exposed to domestic violence, and having a mother using substances were associated with a higher number of health problems. The hierarchical model established the mother's own poor physical health and the child's level of traumatic stress as the strongest predictors of poor child health. Conclusions These two risk factors are amenable to intervention by health care providers who treat children.. posttraumatic-stress| community violence| domestic violence| abuse| women| disorder| ptsd| aggression| depression| witnesses.	MAR-2005	posttraumatic-stress| community violence| domestic violence| abuse| women| disorder| ptsd| aggression| depression| witnesses	Graham-Bermann, SA; Seng, J	Violence exposure and traumatic stress symptoms as additional predictors of health problems in high-risk children		JOURNAL OF PEDIATRICS		POSTTRAUMATIC-STRESS; COMMUNITY VIOLENCE; DOMESTIC VIOLENCE; ABUSE; WOMEN; DISORDER; PTSD; AGGRESSION; DEPRESSION; WITNESSES	Objective To test the hypotheses that both violence and traumatic stress symptoms are associated with negative health status among poor preschool children. Study design This cross-sectional analysis of a Head Start preschool age cohort (n = 160) studied health outcomes parallel to those assessed in the 2001 National Health Interview Survey of child health (asthma, allergy, attention deficit hyperactivity disorder, global appraisal) its well as two stress-related somatic complaints, gastrointestinal problems and headache. Risk factors include sociodemographics, mothers' health factors, extent of exposure to violence and maltreatment, and mother- and teacher-reported traumatic stress symptoms. Results Compared with poor children in the National Health Interview Survey and their Head Start peers, children exposed to violence and those with high levels of traumatic stress had significantly, worse outcomes, in a dose-response relation. Being abused, exposed to domestic violence, and having a mother using substances were associated with a higher number of health problems. The hierarchical model established the mother's own poor physical health and the child's level of traumatic stress as the strongest predictors of poor child health. Conclusions These two risk factors are amenable to intervention by health care providers who treat children.	35	87	2005	6	10.1016/j.jpeds.2004.10.065	Pediatrics
Clinical effects of Lactobacillus acidophilus strain L-92 on perennial allergic rhinitis: A double-blind, placebo-controlled study. Studies in animals have suggested that lactic acid bacteria alleviate allergic diseases, however, little information is available on their clinical effect on allergy in humans. Thus, we examined the efficacy of orally administered Lactobacillus acidophilus strain L-92 (L-92) on perennial allergic rhinitis. In a randomized, double-blind, placebo-controlled clinical trial, 49 patients with perennial allergic rhinitis were randomized to receive either 100 mL of heat-treated fermented milk containing L-92 (n = 25) or acidified milk without lactic acid bacteria (placebo; n = 24) for 8 wk. The severity of symptoms was evaluated based on the changes in the scores of clinical symptoms. Oral administration of milk fermented with L-92 resulted in a statistically significant improvement of nasal symptom-medication scores. Ocular symptom-medication scores of patients in the L-92 intervention group tended to improve compared with those in the placebo group. In addition, clear decreases of the scores of swelling and color of the nasal mucosa were observed in the L-92 intervention group at 6 and 8 wk after the start of ingestion of fermented milk. There were no significant differences in serum antihouse dust mite immunoglobulin E levels nor in T helper type 1/T helper type 2 ratio between the 2 groups. These results suggest that oral administration of L-92 can alleviate the symptoms of perennial allergic rhinitis, however, statistically significant changes were not shown in blood parameters.. lactobacillus acidophilus| perennial allergic rhinitis| double-blind placebo-controlled study|lactic-acid bacteria| regulatory-cells| controlled trial| dendritic cells| atopic disease| t-cells| children| asthma| mice| prevention.	FEB-2005	lactobacillus acidophilus| perennial allergic rhinitis| double-blind placebo-controlled study|lactic-acid bacteria| regulatory-cells| controlled trial| dendritic cells| atopic disease| t-cells| children| asthma| mice| prevention	Ishida, Y; Nakamura, F; Kanzato, H; Sawada, D; Hirata, H; Nishimura, A; Kajimoto, O; Fujiwara, S	Clinical effects of Lactobacillus acidophilus strain L-92 on perennial allergic rhinitis: A double-blind, placebo-controlled study		JOURNAL OF DAIRY SCIENCE	Lactobacillus acidophilus; perennial allergic rhinitis; double-blind placebo-controlled study	LACTIC-ACID BACTERIA; REGULATORY-CELLS; CONTROLLED TRIAL; DENDRITIC CELLS; ATOPIC DISEASE; T-CELLS; CHILDREN; ASTHMA; MICE; PREVENTION	Studies in animals have suggested that lactic acid bacteria alleviate allergic diseases, however, little information is available on their clinical effect on allergy in humans. Thus, we examined the efficacy of orally administered Lactobacillus acidophilus strain L-92 (L-92) on perennial allergic rhinitis. In a randomized, double-blind, placebo-controlled clinical trial, 49 patients with perennial allergic rhinitis were randomized to receive either 100 mL of heat-treated fermented milk containing L-92 (n = 25) or acidified milk without lactic acid bacteria (placebo; n = 24) for 8 wk. The severity of symptoms was evaluated based on the changes in the scores of clinical symptoms. Oral administration of milk fermented with L-92 resulted in a statistically significant improvement of nasal symptom-medication scores. Ocular symptom-medication scores of patients in the L-92 intervention group tended to improve compared with those in the placebo group. In addition, clear decreases of the scores of swelling and color of the nasal mucosa were observed in the L-92 intervention group at 6 and 8 wk after the start of ingestion of fermented milk. There were no significant differences in serum antihouse dust mite immunoglobulin E levels nor in T helper type 1/T helper type 2 ratio between the 2 groups. These results suggest that oral administration of L-92 can alleviate the symptoms of perennial allergic rhinitis, however, statistically significant changes were not shown in blood parameters.	24	87	2005	7		Agriculture; Food Science & Technology
The current state of telemonitoring: A comment on the literature. Telemonitoring, is defined as the use of information technology to monitor patients at a distance. This literature review suggests that the most promising applications for telemonitoring is for chronic illnesses such as cardiopulmonary disease, asthma, and heart failure in the home. Fetal heart rate monitoring and infant cardiopulmonary functions have also been monitored at a distance, as well as coagulation, or the level of activity of elderly people, assessed by the intelligent home monitoring devices. Hospitals, clinics, and prisons all have used telemonitoring, as have ambulances equipped with systems connected to the receiving hospital. Telemonitoring allows reduction of chronic disease complications thanks to a better followup; provides health care services without using hospital beds; and reduces patient travel, time off from work, and overall costs. Several systems have proven to be cost effective. Telemonitoring is also a way of responding to the new needs of home care in an ageing population. Real- time monitoring of patients in ambulances reduces the time to initiate treatment and allows the emergency crew to be better prepared. The obstacles to telemonitoring development include the initial costs of systems, physician licensing, and reimbursement. In the future, virtual reality, immersive environments, haptic feedback and nanotechnology promise new ways in improving the capabilities of telemonitoring.. monitoring-system| telemedicine| internet| care| management| telemetry| patient| everest| top.	FEB-2005	monitoring-system| telemedicine| internet| care| management| telemetry| patient| everest| top	Meystre, S	The current state of telemonitoring: A comment on the literature		TELEMEDICINE JOURNAL AND E-HEALTH		MONITORING-SYSTEM; TELEMEDICINE; INTERNET; CARE; MANAGEMENT; TELEMETRY; PATIENT; EVEREST; TOP	Telemonitoring, is defined as the use of information technology to monitor patients at a distance. This literature review suggests that the most promising applications for telemonitoring is for chronic illnesses such as cardiopulmonary disease, asthma, and heart failure in the home. Fetal heart rate monitoring and infant cardiopulmonary functions have also been monitored at a distance, as well as coagulation, or the level of activity of elderly people, assessed by the intelligent home monitoring devices. Hospitals, clinics, and prisons all have used telemonitoring, as have ambulances equipped with systems connected to the receiving hospital. Telemonitoring allows reduction of chronic disease complications thanks to a better followup; provides health care services without using hospital beds; and reduces patient travel, time off from work, and overall costs. Several systems have proven to be cost effective. Telemonitoring is also a way of responding to the new needs of home care in an ageing population. Real- time monitoring of patients in ambulances reduces the time to initiate treatment and allows the emergency crew to be better prepared. The obstacles to telemonitoring development include the initial costs of systems, physician licensing, and reimbursement. In the future, virtual reality, immersive environments, haptic feedback and nanotechnology promise new ways in improving the capabilities of telemonitoring.	49	87	2005	7	10.1089/tmj.2005.11.63	Health Care Sciences & Services
Improving asthma control through telemedicine: A study of short-message service. Home peak expiratory flow ( PEF) measurement is recommended by asthma guidelines. In a 16-week randomized controlled study on there exists 6 subjects with asthma ( 24.6 +/- 6.5 years old, asthma duration. 6 months), we examined Global System for Mobile Communications ( GSM) mobile telephone short- message service ( SMS) as a novel means of telemedicine in PEF monitoring. All subjects received asthma education, self- management plan, and standard treatment. All measured PEF three times daily and kept a symptom diary. In the study group, therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients. There was no significant difference between the groups in absolute PEF, but PEF variability was significantly smaller in the study group ( 16.12 +/- 6.93% vs. 27.24 +/- 10.01%, p = 0.049). forced expiratory flow in 1 second ( FEV(1); % predicted) in the study group was slightly but significantly increased ( 81.25 +/- 17.31 vs. 77.63 +/- 14.80, p = 0.014) and in the control group, unchanged ( 78.25 +/- 21.09 vs. 78.88 +/- 22.02, p = 0.497). Mean FEV(1) was similar in the two groups both before and after the study. Controls had significantly higher scores for cough ( 1.85 +/- 0.43 vs. 1.42 +/- 0.28, p < 0.05) and night symptoms ( 1.22 +/- 0.23 vs. 0.85 +/- 0.32, p < 0.05). There was no significant difference between the groups in daily consumption of inhaled medicine, forced vital capacity, or compliance. Per patient, per week, the additional cost of follow- up by SMS was A E1.67 ( equivalent to approximately $ 1.30 per 1 Euro), and SMS transmission required 11.5 minutes. Although a study group of 40 patients is needed for the follow- up study to achieve the power of 80% within the 95% confidence interval, we conclude that SMS is a convenient, reliable, affordable, and secure means of telemedicine that may improve asthma control when added to a written action plan and standard follow- up.. peak expiratory flow| self-management| obstruction| medication| education| symptoms| program| health| costs| diary.	FEB-2005	peak expiratory flow| self-management| obstruction| medication| education| symptoms| program| health| costs| diary	Ostojic, V; Cvoriscec, B; Ostojic, SB; Reznikoff, D; Stipic-Markovic, A; Tudjman, Z	Improving asthma control through telemedicine: A study of short-message service		TELEMEDICINE JOURNAL AND E-HEALTH		PEAK EXPIRATORY FLOW; SELF-MANAGEMENT; OBSTRUCTION; MEDICATION; EDUCATION; SYMPTOMS; PROGRAM; HEALTH; COSTS; DIARY	Home peak expiratory flow ( PEF) measurement is recommended by asthma guidelines. In a 16-week randomized controlled study on there exists 6 subjects with asthma ( 24.6 +/- 6.5 years old, asthma duration. 6 months), we examined Global System for Mobile Communications ( GSM) mobile telephone short- message service ( SMS) as a novel means of telemedicine in PEF monitoring. All subjects received asthma education, self- management plan, and standard treatment. All measured PEF three times daily and kept a symptom diary. In the study group, therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients. There was no significant difference between the groups in absolute PEF, but PEF variability was significantly smaller in the study group ( 16.12 +/- 6.93% vs. 27.24 +/- 10.01%, p = 0.049). forced expiratory flow in 1 second ( FEV(1); % predicted) in the study group was slightly but significantly increased ( 81.25 +/- 17.31 vs. 77.63 +/- 14.80, p = 0.014) and in the control group, unchanged ( 78.25 +/- 21.09 vs. 78.88 +/- 22.02, p = 0.497). Mean FEV(1) was similar in the two groups both before and after the study. Controls had significantly higher scores for cough ( 1.85 +/- 0.43 vs. 1.42 +/- 0.28, p < 0.05) and night symptoms ( 1.22 +/- 0.23 vs. 0.85 +/- 0.32, p < 0.05). There was no significant difference between the groups in daily consumption of inhaled medicine, forced vital capacity, or compliance. Per patient, per week, the additional cost of follow- up by SMS was A E1.67 ( equivalent to approximately $ 1.30 per 1 Euro), and SMS transmission required 11.5 minutes. Although a study group of 40 patients is needed for the follow- up study to achieve the power of 80% within the 95% confidence interval, we conclude that SMS is a convenient, reliable, affordable, and secure means of telemedicine that may improve asthma control when added to a written action plan and standard follow- up.	34	87	2005	8	10.1089/tmj.2005.11.28	Health Care Sciences & Services
Efficacy of sublingual allergen vaccination for respiratory allergy in children. Conclusions from one meta-analysis. Background. Sunlingual route, that allows the safe administration of allergen vaccination at home and without injections, is highly attractive alternative to parential delivery, especially amongthe youngest population. However, it's efficiacy in children has been questioned. Objuctive. To evaluate the efficiacy (symptom and medication scores) of sublingual allergen vaccination compared to placebo in pediatric patients. Search strategy: MEDLINE, EMBASE, ISI and the Cochrane Central Register of Controlled trials were explored (completed in january/04) for potentially relevant studies. Selection Criteria: Randomized double blind placebo-controlled clinical trials involving children <= 14 years-old with either rhinitis or asthma of proved allergic aetiology. Data collection and analysis. Two reviewers analyzed independently the eligiblility of studies for inclusions. The combined standardized mean difference (SMD) method was used the random effect model to obtain SMD. However, we also present the SMD values from the fixed effect model. The main outcomes were clinical symptom (asthma, rhinitis and conjunctivitis) and drug requirement scores. Safely, immunological and clinical changes were also reviewed. Results. Seven double blind placebo-controlled trials, enrolling 256 children (129 treatment and 127 placebo recipients), wee analyzed. We observed decreases in symptom (SMD: -1.42 for asthma, -0.44 for rhinitis and -1.49 for conjunctivitis) and medication requirement (SMD - 1.01) scores. Only reductions in asthma (p = 0.01) and drug dosage (p = 0.06) scores reached statistical significance with the random effect model but changes in rhinitis fixed effect model were similar in magnitude (SMD: - 1.60 for asthma, SMD: -0.47 for rhinitis, SMD: -1.09 for conjunctivitis and SMD: 0.54 for drug intake). Safety was constant in all the studies, neither severe nor systemic reactions were observed and oral and gastrointestinal complaints complaints were the most common adverse effects. Conclusion: In children, sublingual delivery of allergen vaccination constitutes a safe and effective alternative to the sublingual route to reduce allergy respiratory symptoms and drug intake. Further studies in this group of age are required to establish the optimal conditions for sublingual allergen vaccination.. sublingual allergen vaccination| immunotherapy| rhinitis| asthma| children| efficacy| meta-analysis|house-dust mite| placebo-controlled evaluation| double-blind| postmarketing surveillance| swallow immunotherapy| pediatric-patients| grass-pollen| asthma| safety| extract.	2005	sublingual allergen vaccination| immunotherapy| rhinitis| asthma| children| efficacy| meta-analysis|house-dust mite| placebo-controlled evaluation| double-blind| postmarketing surveillance| swallow immunotherapy| pediatric-patients| grass-pollen| asthma| safety| extract	Olaguibel, JM; Puebla, MJA	Efficacy of sublingual allergen vaccination for respiratory allergy in children. Conclusions from one meta-analysis		JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY	sublingual allergen vaccination; immunotherapy; rhinitis; asthma; children; efficacy; meta-analysis	HOUSE-DUST MITE; PLACEBO-CONTROLLED EVALUATION; DOUBLE-BLIND; POSTMARKETING SURVEILLANCE; SWALLOW IMMUNOTHERAPY; PEDIATRIC-PATIENTS; GRASS-POLLEN; ASTHMA; SAFETY; EXTRACT	Background. Sunlingual route, that allows the safe administration of allergen vaccination at home and without injections, is highly attractive alternative to parential delivery, especially amongthe youngest population. However, it's efficiacy in children has been questioned. Objuctive. To evaluate the efficiacy (symptom and medication scores) of sublingual allergen vaccination compared to placebo in pediatric patients. Search strategy: MEDLINE, EMBASE, ISI and the Cochrane Central Register of Controlled trials were explored (completed in january/04) for potentially relevant studies. Selection Criteria: Randomized double blind placebo-controlled clinical trials involving children <= 14 years-old with either rhinitis or asthma of proved allergic aetiology. Data collection and analysis. Two reviewers analyzed independently the eligiblility of studies for inclusions. The combined standardized mean difference (SMD) method was used the random effect model to obtain SMD. However, we also present the SMD values from the fixed effect model. The main outcomes were clinical symptom (asthma, rhinitis and conjunctivitis) and drug requirement scores. Safely, immunological and clinical changes were also reviewed. Results. Seven double blind placebo-controlled trials, enrolling 256 children (129 treatment and 127 placebo recipients), wee analyzed. We observed decreases in symptom (SMD: -1.42 for asthma, -0.44 for rhinitis and -1.49 for conjunctivitis) and medication requirement (SMD - 1.01) scores. Only reductions in asthma (p = 0.01) and drug dosage (p = 0.06) scores reached statistical significance with the random effect model but changes in rhinitis fixed effect model were similar in magnitude (SMD: - 1.60 for asthma, SMD: -0.47 for rhinitis, SMD: -1.09 for conjunctivitis and SMD: 0.54 for drug intake). Safety was constant in all the studies, neither severe nor systemic reactions were observed and oral and gastrointestinal complaints complaints were the most common adverse effects. Conclusion: In children, sublingual delivery of allergen vaccination constitutes a safe and effective alternative to the sublingual route to reduce allergy respiratory symptoms and drug intake. Further studies in this group of age are required to establish the optimal conditions for sublingual allergen vaccination.	33	87	2005	8		Allergy; Immunology
Is the hygiene hypothesis still a viable explanation for the increased prevalence of asthma?. The hygiene hypothesis states that a reduced exposure to allergens in early life is solely implicated in the growing propensity for allergy sensitization. Important elements of the hypothesis include helminth infection, exposure to endotoxins, exposure to pets and growing up on a farm. However, the hygiene hypothesis alone does not provide an adequate explanation for the observed increase in allergic disease. For example, in North American inner cities, asthma is increasing among children who live in very poor housing, which might be assumed to be somewhat dirty. In order to explain the increase in asthma, we need to take a broader view and also consider alterations related to the adoption of a western lifestyle. It has been suggested that lifestyle changes related to obesity (e.g. a change in diet) are associated with asthma. Other changes include a progressive decrease in physical activity. This lifestyle factor seems to correlate best with the recent increase in asthma. Clearly, the link between physical activity and asthma needs to be investigated in more detail.. allergen exposure| asthma| hygiene| lifestyle| prevalence|modified th2 response| dog ownership| cat allergen| children| exposure| sensitization| risk| atopy| age| morbidity.	2005	allergen exposure| asthma| hygiene| lifestyle| prevalence|modified th2 response| dog ownership| cat allergen| children| exposure| sensitization| risk| atopy| age| morbidity	Platts-Mills, TAE; Erwin, E; Heymann, P; Woodfolk, J	Is the hygiene hypothesis still a viable explanation for the increased prevalence of asthma?		ALLERGY	allergen exposure; asthma; hygiene; lifestyle; prevalence	MODIFIED TH2 RESPONSE; DOG OWNERSHIP; CAT ALLERGEN; CHILDREN; EXPOSURE; SENSITIZATION; RISK; ATOPY; AGE; MORBIDITY	The hygiene hypothesis states that a reduced exposure to allergens in early life is solely implicated in the growing propensity for allergy sensitization. Important elements of the hypothesis include helminth infection, exposure to endotoxins, exposure to pets and growing up on a farm. However, the hygiene hypothesis alone does not provide an adequate explanation for the observed increase in allergic disease. For example, in North American inner cities, asthma is increasing among children who live in very poor housing, which might be assumed to be somewhat dirty. In order to explain the increase in asthma, we need to take a broader view and also consider alterations related to the adoption of a western lifestyle. It has been suggested that lifestyle changes related to obesity (e.g. a change in diet) are associated with asthma. Other changes include a progressive decrease in physical activity. This lifestyle factor seems to correlate best with the recent increase in asthma. Clearly, the link between physical activity and asthma needs to be investigated in more detail.	39	87	2005	7	10.1111/j.1398-9995.2005.00854.x	Allergy; Immunology
Acute allergen-induced airway remodeling in atopic asthma. Studies in animals and in human atopic skin suggest that allergen challenge may activate acute tissue remodeling changes via transforming growth factor-beta pathways. We determined whether inhalational allergen challenge in subjects with mild asthma induces similar acute changes to the airway epithelial mesenchymal trophic unit (EMTU). Endobronchial mucosal biopsies obtained before and 24 h after challenge were examined by confocal microscopy for extracellular matrix deposition in the reticular basement membrane (RBM). Cells actively involved in extracellular matrix synthesis were identified as immunoreactive to heat shock protein 47, a chaperone of Collagen synthesis. Interleukin-4/13 and transforming growth factor-beta-activated cells were identified by specific antibodies to phosphorylated (phospho-) signal transducer and activator of transcription 6 and phospho-Smad2, respectively. After allergen challenge, there was a significant increase in the number of heat shock protein 47-positive airway fibroblasts (P = 0.003) and in the thickness of tenascin in the RBM (P = 0.031). There were also increases in the number of phospho-Smad2+ epithelial cells (P = 0.04) and nuclear phospho-Smad2+ fibroblasts (P = 0.03), as well as phospho-signal transducer and activator of transcription 6+ epithelial cells (P = 0.03), after allergen challenge. Thus, allergen challenge in patients with mild asthma induces activation of epithelial cells and fibroblasts in the EMTU as well as increased tenascin deposition within the RBM. Airway remodeling in asthma may, in part, result from repeated acute activation of the EMTU by allergen exposure.. basement-membrane| tgf-beta| bronchial biopsies| epithelial-cells| gene-expression| moderate asthma| inflammation| mild| activation| eosinophils.	DEC-2004	basement-membrane| tgf-beta| bronchial biopsies| epithelial-cells| gene-expression| moderate asthma| inflammation| mild| activation| eosinophils	Phipps, S; Benyahia, F; Ou, TT; Barkans, J; Robinson, DS; Kay, AB	Acute allergen-induced airway remodeling in atopic asthma		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		BASEMENT-MEMBRANE; TGF-BETA; BRONCHIAL BIOPSIES; EPITHELIAL-CELLS; GENE-EXPRESSION; MODERATE ASTHMA; INFLAMMATION; MILD; ACTIVATION; EOSINOPHILS	Studies in animals and in human atopic skin suggest that allergen challenge may activate acute tissue remodeling changes via transforming growth factor-beta pathways. We determined whether inhalational allergen challenge in subjects with mild asthma induces similar acute changes to the airway epithelial mesenchymal trophic unit (EMTU). Endobronchial mucosal biopsies obtained before and 24 h after challenge were examined by confocal microscopy for extracellular matrix deposition in the reticular basement membrane (RBM). Cells actively involved in extracellular matrix synthesis were identified as immunoreactive to heat shock protein 47, a chaperone of Collagen synthesis. Interleukin-4/13 and transforming growth factor-beta-activated cells were identified by specific antibodies to phosphorylated (phospho-) signal transducer and activator of transcription 6 and phospho-Smad2, respectively. After allergen challenge, there was a significant increase in the number of heat shock protein 47-positive airway fibroblasts (P = 0.003) and in the thickness of tenascin in the RBM (P = 0.031). There were also increases in the number of phospho-Smad2+ epithelial cells (P = 0.04) and nuclear phospho-Smad2+ fibroblasts (P = 0.03), as well as phospho-signal transducer and activator of transcription 6+ epithelial cells (P = 0.03), after allergen challenge. Thus, allergen challenge in patients with mild asthma induces activation of epithelial cells and fibroblasts in the EMTU as well as increased tenascin deposition within the RBM. Airway remodeling in asthma may, in part, result from repeated acute activation of the EMTU by allergen exposure.	29	87	2004	7	10.1165/rcmb.2004-0193OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
"Regulation of allergy and autoimmunity in helminth infection. Parasitic infections are a major theme in the ""hygiene hypothesis"", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths""-the grouping of multicellular worm parasistes including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit. Parasitic infections are a major theme in the-""hygiene hypothesis"", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths""-the grouping of multicellular worm parasistes including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit.. cytokines| asthma| immunoregulation| parasites|induced airway hyperreactivity| killed mycobacterium-vaccae| t-cell responses| dependent diabetes-mellitus| modified th2 response| house-dust mite| schistosoma-mansoni| mast-cells| immune-responses| eosinophilic inflammation."	FEB-2004	cytokines| asthma| immunoregulation| parasites|induced airway hyperreactivity| killed mycobacterium-vaccae| t-cell responses| dependent diabetes-mellitus| modified th2 response| house-dust mite| schistosoma-mansoni| mast-cells| immune-responses| eosinophilic inflammation	Wilson, MS; Maizels, RM	Regulation of allergy and autoimmunity in helminth infection		CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY	cytokines; asthma; immunoregulation; parasites	INDUCED AIRWAY HYPERREACTIVITY; KILLED MYCOBACTERIUM-VACCAE; T-CELL RESPONSES; DEPENDENT DIABETES-MELLITUS; MODIFIED TH2 RESPONSE; HOUSE-DUST MITE; SCHISTOSOMA-MANSONI; MAST-CELLS; IMMUNE-RESPONSES; EOSINOPHILIC INFLAMMATION	"Parasitic infections are a major theme in the ""hygiene hypothesis"", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths""-the grouping of multicellular worm parasistes including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit. Parasitic infections are a major theme in the-""hygiene hypothesis"", as allergies and autoimmune diseases are less prevalent in countries with higher burdens of helminths and other parasitic organisms. Helminths""-the grouping of multicellular worm parasistes including nematodes, cestodes and trematodes-tend to establish long-lived, chronic infections indicating successful down-modulation of the host immune system. In this review, we describe the intricate immunology of host-helminth interactions and how parasites manipulate immune responses to enhance their survival. In so doing, they often minimise immunopathology and, it is suggested, reduce host susceptibility to, and severity of allergic and autoimmune diseases. Studies on helminth-infected communities and individuals support the hypothesis that an immuno-regulatory network promoted by parasites extends its influence to limiting allergies. Experimental models are now probing more deeply into the area of immune modulation by helminths, and we discuss the likely mechanisms by which helminths could be establishing a strongly regulatory environment. Understanding and harnessing the modulatory capacity of helminths may uncover novel therapeutic interventions, mimicking and exploiting their evolution for our benefit."	161	87	2004	16	10.1385/CRIAI:26:1:35	Allergy; Immunology
Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation. Asthma is associated with airway remodeling. Evidence of platelet recruitment to the lungs of asthmatics after allergen exposure suggests platelets participate in various aspects of asthma; although their importance is unknown in the context of airway remodeling, their involvement in atherosclerosis is established. Studies from our laboratory have shown a requirement for platelets in pulmonary leukocyte recruitment in a murine model of allergic lung inflammation. Presently, the effects of platelet depletion and corticosteroid administration on airway remodeling and lung function were examined. Ovalbumin (OVA)-sensitized mice, exposed to aerosolized OVA for 8 weeks, demonstrated epithelial and smooth muscle thickening, and subepithelial reticular fiber deposition in the distal airways. The depletion of platelets via an immunologic (antiplatelet antisera) or nonimmunologic (busulfan) method, markedly reduced airway remodeling. In contrast, dexamethasone administration did not affect epithelial thickening or subepithelial fibrosis, despite significantly inhibiting leukocyte recruitment. Thus, pathways leading to certain aspects of airway remodeling may not depend on leukocyte recruitment, whereas platelet activation is obligatory. OVA-sensitized mice exhibited airway hyperresponsiveness (AHR) compared with sham-sensitized mice following chronic OVA exposure. Neither platelet depletion nor dexamethasone administration inhibited chronic AHR; thus, mechanisms other than inflammation and airway remodeling may be involved in the pathogenesis of chronic AHR.. smooth-muscle-cells| growth-factor| bronchial-asthma| mucosal biopsies| mouse model| mild asthma| in-vivo| proliferation| hyperplasia| mice.	JAN 15-2004	smooth-muscle-cells| growth-factor| bronchial-asthma| mucosal biopsies| mouse model| mild asthma| in-vivo| proliferation| hyperplasia| mice	Pitchford, SC; Riffo-Vasquez, Y; Sousa, A; Momi, S; Gresele, P; Spina, D; Page, CP	Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation		BLOOD		SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR; BRONCHIAL-ASTHMA; MUCOSAL BIOPSIES; MOUSE MODEL; MILD ASTHMA; IN-VIVO; PROLIFERATION; HYPERPLASIA; MICE	Asthma is associated with airway remodeling. Evidence of platelet recruitment to the lungs of asthmatics after allergen exposure suggests platelets participate in various aspects of asthma; although their importance is unknown in the context of airway remodeling, their involvement in atherosclerosis is established. Studies from our laboratory have shown a requirement for platelets in pulmonary leukocyte recruitment in a murine model of allergic lung inflammation. Presently, the effects of platelet depletion and corticosteroid administration on airway remodeling and lung function were examined. Ovalbumin (OVA)-sensitized mice, exposed to aerosolized OVA for 8 weeks, demonstrated epithelial and smooth muscle thickening, and subepithelial reticular fiber deposition in the distal airways. The depletion of platelets via an immunologic (antiplatelet antisera) or nonimmunologic (busulfan) method, markedly reduced airway remodeling. In contrast, dexamethasone administration did not affect epithelial thickening or subepithelial fibrosis, despite significantly inhibiting leukocyte recruitment. Thus, pathways leading to certain aspects of airway remodeling may not depend on leukocyte recruitment, whereas platelet activation is obligatory. OVA-sensitized mice exhibited airway hyperresponsiveness (AHR) compared with sham-sensitized mice following chronic OVA exposure. Neither platelet depletion nor dexamethasone administration inhibited chronic AHR; thus, mechanisms other than inflammation and airway remodeling may be involved in the pathogenesis of chronic AHR.	60	87	2004	9	10.1182/blood-2003-05-1707	Hematology
Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma. The aim of this study was to examine the relationship between the structural changes in large and small airways in asymptomatic asthmatics quantified by high-resolution computed tomography (HRCT) and airflow obstruction. The bronchial wall thickness at the trunk of the apical bronchus (B1) of the right upper lobe was used for assessment of the large airways. Air trapping, evaluated by the ratio of the average. CT-determined values for the bilateral upper and lower lung segments at full expiration to that at full inspiration (E/I ratio), was used for assessment of the small airways. Measurements were obtained with a helical HRCT in 24 asymptomatic asthmatics followed by optimal treatment with inhaled and/or oral corticosteroids for >6 months. Prior (20-30 min) to the HRCT examination, all patients were given an inhaled bronchodilator. The ratio of airway wall thickness to outer diameter (T/D) and the percentage wall area (WA%) at the B1 bronchus and the E/I ratio were significantly greater for the 14 asthmatics with deficient reversible airflow obstruction (forced expiratory volume in one second (FEV1) <80% prediced or FEV1/forced vital capacity <70% after bronchodilator inhalation) than for the 10 asthmatics with normal spirometry and seven normal subjects. T/D, WA%, and E/I ratio showed significant negative correlations with FEV1 % pred after bronchodilator inhalation. The E/I ratio also showed significant positive correlations with T/D, WA%, and residual volume/total lung capacity. These findings suggest that, in spite of optimal treatment, structural changes in both large and small airways may simultaneously occur in asthmatics with deficient reversible airflow obstruction.. air trapping| airflow obstruction| airway remodelling| airway wall| bronchial asthma| high-resolution computed tomography|resolution computed-tomography| obstructive pulmonary-disease| flow obstruction| bronchial-asthma| function tests| fatal asthma| emphysema| ct| hyperresponsiveness| dimensions.	DEC-2003	air trapping| airflow obstruction| airway remodelling| airway wall| bronchial asthma| high-resolution computed tomography|resolution computed-tomography| obstructive pulmonary-disease| flow obstruction| bronchial-asthma| function tests| fatal asthma| emphysema| ct| hyperresponsiveness| dimensions	Gono, H; Fujimoto, K; Kawakami, S; Kubo, K	Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma		EUROPEAN RESPIRATORY JOURNAL	air trapping; airflow obstruction; airway remodelling; airway wall; bronchial asthma; high-resolution computed tomography	RESOLUTION COMPUTED-TOMOGRAPHY; OBSTRUCTIVE PULMONARY-DISEASE; FLOW OBSTRUCTION; BRONCHIAL-ASTHMA; FUNCTION TESTS; FATAL ASTHMA; EMPHYSEMA; CT; HYPERRESPONSIVENESS; DIMENSIONS	The aim of this study was to examine the relationship between the structural changes in large and small airways in asymptomatic asthmatics quantified by high-resolution computed tomography (HRCT) and airflow obstruction. The bronchial wall thickness at the trunk of the apical bronchus (B1) of the right upper lobe was used for assessment of the large airways. Air trapping, evaluated by the ratio of the average. CT-determined values for the bilateral upper and lower lung segments at full expiration to that at full inspiration (E/I ratio), was used for assessment of the small airways. Measurements were obtained with a helical HRCT in 24 asymptomatic asthmatics followed by optimal treatment with inhaled and/or oral corticosteroids for >6 months. Prior (20-30 min) to the HRCT examination, all patients were given an inhaled bronchodilator. The ratio of airway wall thickness to outer diameter (T/D) and the percentage wall area (WA%) at the B1 bronchus and the E/I ratio were significantly greater for the 14 asthmatics with deficient reversible airflow obstruction (forced expiratory volume in one second (FEV1) <80% prediced or FEV1/forced vital capacity <70% after bronchodilator inhalation) than for the 10 asthmatics with normal spirometry and seven normal subjects. T/D, WA%, and E/I ratio showed significant negative correlations with FEV1 % pred after bronchodilator inhalation. The E/I ratio also showed significant positive correlations with T/D, WA%, and residual volume/total lung capacity. These findings suggest that, in spite of optimal treatment, structural changes in both large and small airways may simultaneously occur in asthmatics with deficient reversible airflow obstruction.	27	87	2003	7	10.1183/09031936.03.00085302	Respiratory System
Mechanical stress triggers selective release of fibrotic mediators from bronchial epithelium. Transforming growth factor-beta (TGF-beta) and endothelin (ET) are found in elevated amounts in the airways of individuals with asthma. The cellular source of these peptides and their role in mediating the airway fibrosis of chronic asthma are unknown. In response to mechanical stresses similar to those occurring in vivo during airway constriction, bronchial epithelial cells increase the steady-state level of mRNA for both ET-1 and ET-2, followed by increased release of ET protein. Mechanical stress also enhances release of TGF-beta2 from a preformed cell-associated pool. TGF-beta2 and ET act individually and, more importantly, synergistically to promote fibrotic protein synthesis in reporter fibroblasts. To confirm the role of these intermediates in stress-induced fibrosis, conditioned medium from mechanically stressed bronchial epithelial cells was shown to elicit fibrotic protein synthesis in reporter fibroblasts; this effect was significantly inhibited by combined treatment with ET receptor antagonists and a neutralizing antibody to TGF-beta2. These data are consistent with a primary pathogenic role for mechanical stress-induced release of both TGF-beta2 and ET in the subepithelial fibrosis that characterizes chronic asthma.. growth-factor-beta| bronchoalveolar lavage fluid| induced cardiomyocyte hypertrophy| endothelin-1 gene-expression| air-flow obstruction| protein-kinase-c| latent tgf-beta| extracellular-matrix| transforming growth-factor-beta-1| cell-proliferation.	FEB-2003	growth-factor-beta| bronchoalveolar lavage fluid| induced cardiomyocyte hypertrophy| endothelin-1 gene-expression| air-flow obstruction| protein-kinase-c| latent tgf-beta| extracellular-matrix| transforming growth-factor-beta-1| cell-proliferation	Tschumperlin, DJ; Shively, JD; Kikuchi, T; Drazen, JM	Mechanical stress triggers selective release of fibrotic mediators from bronchial epithelium		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY		GROWTH-FACTOR-BETA; BRONCHOALVEOLAR LAVAGE FLUID; INDUCED CARDIOMYOCYTE HYPERTROPHY; ENDOTHELIN-1 GENE-EXPRESSION; AIR-FLOW OBSTRUCTION; PROTEIN-KINASE-C; LATENT TGF-BETA; EXTRACELLULAR-MATRIX; TRANSFORMING GROWTH-FACTOR-BETA-1; CELL-PROLIFERATION	Transforming growth factor-beta (TGF-beta) and endothelin (ET) are found in elevated amounts in the airways of individuals with asthma. The cellular source of these peptides and their role in mediating the airway fibrosis of chronic asthma are unknown. In response to mechanical stresses similar to those occurring in vivo during airway constriction, bronchial epithelial cells increase the steady-state level of mRNA for both ET-1 and ET-2, followed by increased release of ET protein. Mechanical stress also enhances release of TGF-beta2 from a preformed cell-associated pool. TGF-beta2 and ET act individually and, more importantly, synergistically to promote fibrotic protein synthesis in reporter fibroblasts. To confirm the role of these intermediates in stress-induced fibrosis, conditioned medium from mechanically stressed bronchial epithelial cells was shown to elicit fibrotic protein synthesis in reporter fibroblasts; this effect was significantly inhibited by combined treatment with ET receptor antagonists and a neutralizing antibody to TGF-beta2. These data are consistent with a primary pathogenic role for mechanical stress-induced release of both TGF-beta2 and ET in the subepithelial fibrosis that characterizes chronic asthma.	55	87	2003	8	10.1165/rcmb.2002-0121OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Nickel sensitization in adolescents and association with ear piercing, use of dental braces and hand eczema. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS). The prevalence of nickel allergy (sensitization) and the associations with ear piercing, use of dental braces and hand eczema were assessed in a cohort of 1, 501 8th grade schoolchildren (aged 12-16 years) in Odense, Denmark. Nickel allergy was found in 8.6% and was clinically relevant in 69% of cases. Nickel allergy was found most frequently in girls and the association with ear piercing was confirmed. Application of dental braces (oral nickel exposure) prior to ear piercing (cutaneous nickel exposure) was associated with a significantly reduced prevalence of nickel allergy. In adolescents a significant association was found between hand eczema and nickel allergy. A follow-up study of this population is planned in order to assess the course and development of contact dermatitis, hand eczema and atopic diseases in adulthood and after choice of occupation.. schoolchildren| atopic dermatitis| inhalant allergy| hand eczema| multivariate graphical analysis|north norwegian schoolchildren| allergic contact-dermatitis| children| sensitivity| population| prevalence| history| tests.	SEP-2002	schoolchildren| atopic dermatitis| inhalant allergy| hand eczema| multivariate graphical analysis|north norwegian schoolchildren| allergic contact-dermatitis| children| sensitivity| population| prevalence| history| tests	Mortz, CG; Lauritsen, JM; Bindslev-Jensen, C; Andersen, KE	Nickel sensitization in adolescents and association with ear piercing, use of dental braces and hand eczema. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS)		ACTA DERMATO-VENEREOLOGICA	schoolchildren; atopic dermatitis; inhalant allergy; hand eczema; multivariate graphical analysis	NORTH NORWEGIAN SCHOOLCHILDREN; ALLERGIC CONTACT-DERMATITIS; CHILDREN; SENSITIVITY; POPULATION; PREVALENCE; HISTORY; TESTS	The prevalence of nickel allergy (sensitization) and the associations with ear piercing, use of dental braces and hand eczema were assessed in a cohort of 1, 501 8th grade schoolchildren (aged 12-16 years) in Odense, Denmark. Nickel allergy was found in 8.6% and was clinically relevant in 69% of cases. Nickel allergy was found most frequently in girls and the association with ear piercing was confirmed. Application of dental braces (oral nickel exposure) prior to ear piercing (cutaneous nickel exposure) was associated with a significantly reduced prevalence of nickel allergy. In adolescents a significant association was found between hand eczema and nickel allergy. A follow-up study of this population is planned in order to assess the course and development of contact dermatitis, hand eczema and atopic diseases in adulthood and after choice of occupation.	42	87	2002	6	10.1080/000155502320624096	Dermatology
Indoor exposure to molds and allergic sensitization. Evidence that indoor dampness and mold growth are associated with respiratory health has been accumulating, but few studies have been able to examine health risks in relation to measured levels of indoor mold exposure. In particular, little is known about the contribution of indoor molds to the development of allergic sensitization. As a part of an ongoing study examining the effects of ambient air pollutants on respiratory health and atopic diseases in German school children, we examined the relation between viable mold levels indoors and allergic sensitization in 272 children. We examined whether allergic sensitization in children is associated with higher fungal spore count in settled house dust sampled from living room floors. Adjusting for age, sex, parental education, region of residency, and parental history of atopy, we found that mold spore counts for Cladosporium and Aspergillus were associated with an increased risk of allergic sensitization. Sensitized children exposed to high levels of mold spores (> 90th percentile) were more likely to suffer from symptoms of rhinoconjunctivitis. We conclude that elevated indoor concentrations of molds in wintertime might play a role in increasing the risk of developing atopic symptoms and allergic sensitization not only to molds but also to other common, inhaled allergens. These effects were strongest in the group of children who had lived in the same home since birth.. allergic sensitization| house dust| indoor allergen exposure| molds|in-house dust| reported home dampness| respiratory symptoms| bronchial hyperresponsiveness| residential characteristics| childhood asthma| health| children| fungi| propagules.	JUL-2002	allergic sensitization| house dust| indoor allergen exposure| molds|in-house dust| reported home dampness| respiratory symptoms| bronchial hyperresponsiveness| residential characteristics| childhood asthma| health| children| fungi| propagules	Jacob, B; Ritz, B; Gehring, U; Koch, A; Bischof, W; Wichmann, HE; Heinrich, J	Indoor exposure to molds and allergic sensitization		ENVIRONMENTAL HEALTH PERSPECTIVES	allergic sensitization; house dust; indoor allergen exposure; molds	IN-HOUSE DUST; REPORTED HOME DAMPNESS; RESPIRATORY SYMPTOMS; BRONCHIAL HYPERRESPONSIVENESS; RESIDENTIAL CHARACTERISTICS; CHILDHOOD ASTHMA; HEALTH; CHILDREN; FUNGI; PROPAGULES	Evidence that indoor dampness and mold growth are associated with respiratory health has been accumulating, but few studies have been able to examine health risks in relation to measured levels of indoor mold exposure. In particular, little is known about the contribution of indoor molds to the development of allergic sensitization. As a part of an ongoing study examining the effects of ambient air pollutants on respiratory health and atopic diseases in German school children, we examined the relation between viable mold levels indoors and allergic sensitization in 272 children. We examined whether allergic sensitization in children is associated with higher fungal spore count in settled house dust sampled from living room floors. Adjusting for age, sex, parental education, region of residency, and parental history of atopy, we found that mold spore counts for Cladosporium and Aspergillus were associated with an increased risk of allergic sensitization. Sensitized children exposed to high levels of mold spores (> 90th percentile) were more likely to suffer from symptoms of rhinoconjunctivitis. We conclude that elevated indoor concentrations of molds in wintertime might play a role in increasing the risk of developing atopic symptoms and allergic sensitization not only to molds but also to other common, inhaled allergens. These effects were strongest in the group of children who had lived in the same home since birth.	37	87	2002	7		Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
The mycotoxins citrinin, gliotoxin, and patulin affect interferon-gamma rather than interleukin-4 production in human blood cells. Exposure to molds diminishes the numbers of T-helper type 1 (Th1) cells in the peripheral blood of children and is a risk factor for the development of allergic diseases (results of LARS: Leipzig Allergy Risk Children Study, Mueller et al. 2002). We hypothesized that mycotoxins are responsible for this effect and therefore investigated the influence of citrinin, gliotoxin, and patulin on human peripheral blood mononuclear cells (PBMC). CD3/CD28-stimulated PBMC of healthy donors were incubated for 24 h with the mycotoxins in serial dilutions and triplicates. Vitality and proliferation were tested using the MTT assay and T-cell function by the expression of cytokines (ELISA, intracellular cytokine staining, and real-time polymerase chain reaction (RT-PCR) for interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). The cytokine secretion was inhibited at concentrations 2-130 times lower compared to vitality (ELISA versus MTT assay). The strongest inhibition of cytokine expression was found for IFN-gamma: 8.3 mug/mL citrinin, 34.2 ng/mL gliotoxin, and 64.8 ng/mL patulin caused a 50% inhibition of the IFN-gamma release (50% inhibitory dose, ID50). For IL-4 release the corresponding ID50 values were 21.6 mug/mL citrinin, 82.8 ng/mL gliotoxin, and 243.2 ng/mL patulin. Furthermore, 3 ng/mL patulin caused a significant increase of IL-4 but a significant suppression of IFN-gamma. On the mRNA level, after 24 h an unaltered or enhanced IL-4 was observed compared to a reduced IFN-gamma expression. Using a method of intracellular cytokine staining, we were able to show that the described effects are caused by a reduction of the number of IFN-gamma-producing T lymphocytes rather than by a reduced functional capacity of the single cell. We suggest that mycotoxins primarily cause stronger inhibition of IFN-gamma-producing Th1 cells, which may lead to T-cell polarization toward the Th2 phenotype and may raise the risk for the development of allergies. (C) 2002 Wiley Periodicals, Inc.. mycotoxins| citrinin| gliotoxin| patulin| th1 cells| th2 cells| il-4| ifn-gamma| cytokine immunotoxicity|respiratory health| kappa-b| fungi| risk| proliferation| children| damp.	JUN-2002	mycotoxins| citrinin| gliotoxin| patulin| th1 cells| th2 cells| il-4| ifn-gamma| cytokine immunotoxicity|respiratory health| kappa-b| fungi| risk| proliferation| children| damp	Wichmann, G; Herbarth, O; Lehmann, I	The mycotoxins citrinin, gliotoxin, and patulin affect interferon-gamma rather than interleukin-4 production in human blood cells		ENVIRONMENTAL TOXICOLOGY	mycotoxins; citrinin; gliotoxin; patulin; Th1 cells; Th2 cells; IL-4; IFN-gamma; cytokine immunotoxicity	RESPIRATORY HEALTH; KAPPA-B; FUNGI; RISK; PROLIFERATION; CHILDREN; DAMP	Exposure to molds diminishes the numbers of T-helper type 1 (Th1) cells in the peripheral blood of children and is a risk factor for the development of allergic diseases (results of LARS: Leipzig Allergy Risk Children Study, Mueller et al. 2002). We hypothesized that mycotoxins are responsible for this effect and therefore investigated the influence of citrinin, gliotoxin, and patulin on human peripheral blood mononuclear cells (PBMC). CD3/CD28-stimulated PBMC of healthy donors were incubated for 24 h with the mycotoxins in serial dilutions and triplicates. Vitality and proliferation were tested using the MTT assay and T-cell function by the expression of cytokines (ELISA, intracellular cytokine staining, and real-time polymerase chain reaction (RT-PCR) for interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). The cytokine secretion was inhibited at concentrations 2-130 times lower compared to vitality (ELISA versus MTT assay). The strongest inhibition of cytokine expression was found for IFN-gamma: 8.3 mug/mL citrinin, 34.2 ng/mL gliotoxin, and 64.8 ng/mL patulin caused a 50% inhibition of the IFN-gamma release (50% inhibitory dose, ID50). For IL-4 release the corresponding ID50 values were 21.6 mug/mL citrinin, 82.8 ng/mL gliotoxin, and 243.2 ng/mL patulin. Furthermore, 3 ng/mL patulin caused a significant increase of IL-4 but a significant suppression of IFN-gamma. On the mRNA level, after 24 h an unaltered or enhanced IL-4 was observed compared to a reduced IFN-gamma expression. Using a method of intracellular cytokine staining, we were able to show that the described effects are caused by a reduction of the number of IFN-gamma-producing T lymphocytes rather than by a reduced functional capacity of the single cell. We suggest that mycotoxins primarily cause stronger inhibition of IFN-gamma-producing Th1 cells, which may lead to T-cell polarization toward the Th2 phenotype and may raise the risk for the development of allergies. (C) 2002 Wiley Periodicals, Inc.	23	87	2002	8	10.1002/tox.10050	Environmental Sciences & Ecology; Toxicology; Water Resources
B-2-agonist tolerance and exercise-induced bronchospasm. The effect of regular inhaled beta-agonist on the treatment of exercise-induced bronchoconstriction was studied. Eight subjects with exercise-induced bronchoconstriction took 1 week each of salbutamol 200 mug qid or placebo in a random-order, double-blind, crossover study. They then withheld this treatment for 8 hours before performing a dry-air, sub-maximal exercise challenge at a work-rate previously shown to induce a 15% fall in forced expiratory volume in 1 second (FEV1). Five minutes after exercise, they inhaled salbutamol 100, 100, and 200 mug at 5-minute intervals. The mean pre-exercise FEV1 was similar on both study days. However, pretreatment for 1 week with salbutamol led to a significantly greater fall in FEV1 after exercise. The FEV1 remained lower than during the placebo arm despite the administration of salbutamol after exercise. This difference persisted 25 minutes after exercise. It is concluded that regular beta-agonist treatment leads to Increased exercise-induced bronchoconstriction and a suboptimal bronchodilator response to beta-agonist. The data suggest that previous regular beta-agonist treatment may lead to a failure to respond to emergency bronchodilator treatment during an acute asthma attack and support current opinion that regular short-acting beta-agonist therapy should not be used to treat asthma.. asthma| exercise-induced| adrenergic beta-agonists| tolerance|regular inhaled albuterol| induced bronchoconstriction| asthmatic subjects| bronchodilator| salmeterol| subsensitivity| terbutaline| budesonide| salbutamol| responses.	APR 15-2002	asthma| exercise-induced| adrenergic beta-agonists| tolerance|regular inhaled albuterol| induced bronchoconstriction| asthmatic subjects| bronchodilator| salmeterol| subsensitivity| terbutaline| budesonide| salbutamol| responses	Hancox, RJ; Subbarao, P; Kamada, D; Watson, RM; Hargreave, FE; Inman, MD	B-2-agonist tolerance and exercise-induced bronchospasm		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; exercise-induced; adrenergic beta-agonists; tolerance	REGULAR INHALED ALBUTEROL; INDUCED BRONCHOCONSTRICTION; ASTHMATIC SUBJECTS; BRONCHODILATOR; SALMETEROL; SUBSENSITIVITY; TERBUTALINE; BUDESONIDE; SALBUTAMOL; RESPONSES	The effect of regular inhaled beta-agonist on the treatment of exercise-induced bronchoconstriction was studied. Eight subjects with exercise-induced bronchoconstriction took 1 week each of salbutamol 200 mug qid or placebo in a random-order, double-blind, crossover study. They then withheld this treatment for 8 hours before performing a dry-air, sub-maximal exercise challenge at a work-rate previously shown to induce a 15% fall in forced expiratory volume in 1 second (FEV1). Five minutes after exercise, they inhaled salbutamol 100, 100, and 200 mug at 5-minute intervals. The mean pre-exercise FEV1 was similar on both study days. However, pretreatment for 1 week with salbutamol led to a significantly greater fall in FEV1 after exercise. The FEV1 remained lower than during the placebo arm despite the administration of salbutamol after exercise. This difference persisted 25 minutes after exercise. It is concluded that regular beta-agonist treatment leads to Increased exercise-induced bronchoconstriction and a suboptimal bronchodilator response to beta-agonist. The data suggest that previous regular beta-agonist treatment may lead to a failure to respond to emergency bronchodilator treatment during an acute asthma attack and support current opinion that regular short-acting beta-agonist therapy should not be used to treat asthma.	14	87	2002	3	10.1164/rccm.200111-091BC	General & Internal Medicine; Respiratory System
Understanding fragrance allergy using an exposure-based risk assessment approach. Conducting a sound skin sensitization risk assessment prior to the introduction of new ingredients and products into the market place is essential. The process by which low-molecular-weight chemicals induce and elicit skin sensitization is dependent on many factors, including the ability of the chemical to penetrate the skin, react with protein, and trigger a cell-mediated immune response. Based on our chemical, cellular and molecular understanding of allergic contact dermatitis, it is possible to carry out a quantitative risk assessment. Specifically, by estimating the exposure to the allergen and its allergenic potency, it is feasible to assess quantitatively the sensitization risk of an ingredient in a particular product type. This paper focuses on applying exposure-based risk assessment tools to understanding fragrance allergy for 2 hypothetical products containing the fragrance allergen cinnamic aldehyde. The risk assessment process predicts that an eau de toilette leave-on product containing 1000 ppm or more cinnamic aldehyde would pose an unacceptable risk of induction of skin sensitization, while a shampoo, containing the same level of cinnamic aldehyde, would pose an acceptable risk of induction of skin sensitization, based on limited exposure to the ingredient from a rinse-off product application.. skin| allergic contact sensitization| fragrances| exposure| potency| risk assessment| margin of safety|lymph-node assay| sodium lauryl sulfate| skin sensitization risk| contact sensitization| cinnamic-aldehyde| guinea-pig| activation| dermatitis| responses| tests.	DEC-2001	skin| allergic contact sensitization| fragrances| exposure| potency| risk assessment| margin of safety|lymph-node assay| sodium lauryl sulfate| skin sensitization risk| contact sensitization| cinnamic-aldehyde| guinea-pig| activation| dermatitis| responses| tests	Gerberick, GF; Robinson, MK; Felter, SP; White, IR; Basketter, DA	Understanding fragrance allergy using an exposure-based risk assessment approach		CONTACT DERMATITIS	skin; allergic contact sensitization; fragrances; exposure; potency; risk assessment; margin of safety	LYMPH-NODE ASSAY; SODIUM LAURYL SULFATE; SKIN SENSITIZATION RISK; CONTACT SENSITIZATION; CINNAMIC-ALDEHYDE; GUINEA-PIG; ACTIVATION; DERMATITIS; RESPONSES; TESTS	Conducting a sound skin sensitization risk assessment prior to the introduction of new ingredients and products into the market place is essential. The process by which low-molecular-weight chemicals induce and elicit skin sensitization is dependent on many factors, including the ability of the chemical to penetrate the skin, react with protein, and trigger a cell-mediated immune response. Based on our chemical, cellular and molecular understanding of allergic contact dermatitis, it is possible to carry out a quantitative risk assessment. Specifically, by estimating the exposure to the allergen and its allergenic potency, it is feasible to assess quantitatively the sensitization risk of an ingredient in a particular product type. This paper focuses on applying exposure-based risk assessment tools to understanding fragrance allergy for 2 hypothetical products containing the fragrance allergen cinnamic aldehyde. The risk assessment process predicts that an eau de toilette leave-on product containing 1000 ppm or more cinnamic aldehyde would pose an unacceptable risk of induction of skin sensitization, while a shampoo, containing the same level of cinnamic aldehyde, would pose an acceptable risk of induction of skin sensitization, based on limited exposure to the ingredient from a rinse-off product application.	50	87	2001	8	10.1034/j.1600-0536.2001.450603.x	Allergy; Dermatology
Fluticasone inhibits but does not reverse allergen-induced structural airway changes. Ethical and technical reasons limit the possibility of evaluating the effects of inhaled corticosteroids on structural changes in airways of humans with asthma. We therefore evaluated whether fluticasone propionate (FP) modifies airway remodeling, induced by repeated allergen exposure in rats. Sensitized EN-rats were exposed to aerosolized ovalbumin (OA) for 2 wk. To assess the effect of FP on the development of or on established airway remodeling, animals were treated with aerosolized FP or placebo during allergen exposure or for 2 wk afterward. Compared with animals exposed to phosphate-buffered saline (PBS), OA-challenged animals developed an increase in total airway wall area, enhanced fibronectin deposition, epithelial cell proliferation, goblet cell hyperplasia, and airway hyperresponsiveness. Concomitant treatment with FP decreased all allergen-induced structural changes without being able to reverse them to normal. Initiating FP treatment after the allergen exposure had no effect on any of the OA-induced structural airway changes. The increase in total airway wall area, enhanced fibronectin deposition, and epithelial cell proliferation persisted. The goblet cell hyperplasia disappeared spontaneously. In conclusion, concomitant treatment with FP partly inhibits structural airway changes as well as hyperresponsiveness induced by OA exposure. Post hoc treatment fails to reverse established airway remodeling.. brown-norway rats| inhaled corticosteroids| smooth-muscle| murine model| mild asthma| subepithelial fibrosis| basement-membrane| antigen challenge| bronchial-asthma| term treatment.	MAR-2001	brown-norway rats| inhaled corticosteroids| smooth-muscle| murine model| mild asthma| subepithelial fibrosis| basement-membrane| antigen challenge| bronchial-asthma| term treatment	Vanacker, NJ; Palmans, E; Kips, JC; Pauwels, RA	Fluticasone inhibits but does not reverse allergen-induced structural airway changes		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		BROWN-NORWAY RATS; INHALED CORTICOSTEROIDS; SMOOTH-MUSCLE; MURINE MODEL; MILD ASTHMA; SUBEPITHELIAL FIBROSIS; BASEMENT-MEMBRANE; ANTIGEN CHALLENGE; BRONCHIAL-ASTHMA; TERM TREATMENT	Ethical and technical reasons limit the possibility of evaluating the effects of inhaled corticosteroids on structural changes in airways of humans with asthma. We therefore evaluated whether fluticasone propionate (FP) modifies airway remodeling, induced by repeated allergen exposure in rats. Sensitized EN-rats were exposed to aerosolized ovalbumin (OA) for 2 wk. To assess the effect of FP on the development of or on established airway remodeling, animals were treated with aerosolized FP or placebo during allergen exposure or for 2 wk afterward. Compared with animals exposed to phosphate-buffered saline (PBS), OA-challenged animals developed an increase in total airway wall area, enhanced fibronectin deposition, epithelial cell proliferation, goblet cell hyperplasia, and airway hyperresponsiveness. Concomitant treatment with FP decreased all allergen-induced structural changes without being able to reverse them to normal. Initiating FP treatment after the allergen exposure had no effect on any of the OA-induced structural airway changes. The increase in total airway wall area, enhanced fibronectin deposition, and epithelial cell proliferation persisted. The goblet cell hyperplasia disappeared spontaneously. In conclusion, concomitant treatment with FP partly inhibits structural airway changes as well as hyperresponsiveness induced by OA exposure. Post hoc treatment fails to reverse established airway remodeling.	39	87	2001	6		General & Internal Medicine; Respiratory System
How can thermal processing modify the antigenicity of proteins?. This paper is a brief review of thermally induced covalent modifications to proteins in foods, focussing mainly on the advanced glycation end-products (AGE) of the Maillard reaction. Most foods are subjected to thermal processing, either in the home or during their production/manufacture. Thermal processing provides many beneficial effects, but also brings about major changes in allergenicity. Far from being a general way to decrease allergenic risk, thermal processing is as likely to increase allergenicity as to reduce it, through the introduction of neoantigens. These changes are highly complex and not easily predictable, but there are a number of major chemical pathways that lead to distinct patterns of modification. Perhaps the most important of these is through the reaction of protein amino groups with sugars, leading to an impressive cocktail of AGE-modified protein derivatives. These are antigenic and many of the important neoantigens found in cooked or stored foods are probably such Maillard reaction products. A deeper understanding of thermally induced chemical changes is essential for more advanced risk assessments, more effective QC protocols, production of more relevant diagnostic allergen extracts and the development of novel protein engineering and therapeutic approaches to minimise allergenic risk.. antigenicity| thermal processing|heated pecan nut| maillard reaction| neoallergens| glycation| n-epsilon-(carboxymethyl)lysine| antibodies| products.	2001	antigenicity| thermal processing|heated pecan nut| maillard reaction| neoallergens| glycation| n-epsilon-(carboxymethyl)lysine| antibodies| products	Davis, PJ; Smales, CM; James, DC	How can thermal processing modify the antigenicity of proteins?		ALLERGY	antigenicity; thermal processing	HEATED PECAN NUT; MAILLARD REACTION; NEOALLERGENS; GLYCATION; N-EPSILON-(CARBOXYMETHYL)LYSINE; ANTIBODIES; PRODUCTS	This paper is a brief review of thermally induced covalent modifications to proteins in foods, focussing mainly on the advanced glycation end-products (AGE) of the Maillard reaction. Most foods are subjected to thermal processing, either in the home or during their production/manufacture. Thermal processing provides many beneficial effects, but also brings about major changes in allergenicity. Far from being a general way to decrease allergenic risk, thermal processing is as likely to increase allergenicity as to reduce it, through the introduction of neoantigens. These changes are highly complex and not easily predictable, but there are a number of major chemical pathways that lead to distinct patterns of modification. Perhaps the most important of these is through the reaction of protein amino groups with sugars, leading to an impressive cocktail of AGE-modified protein derivatives. These are antigenic and many of the important neoantigens found in cooked or stored foods are probably such Maillard reaction products. A deeper understanding of thermally induced chemical changes is essential for more advanced risk assessments, more effective QC protocols, production of more relevant diagnostic allergen extracts and the development of novel protein engineering and therapeutic approaches to minimise allergenic risk.	20	87	2001	5	10.1034/j.1398-9995.2001.00918.x	Allergy; Immunology
Prevalence of asthma symptoms in Latin America: The International Study of Asthma and Allergies in Childhood (ISAAC). The prevalence of respiratory symptoms indicative of asthma in children from Latin America has been largely ignored. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), 17 centers in 9 different Latin American countries participated in the study, and data from 52,549 written questionnaires (WQ) in children aged 13-14 years and from 36,264 WQ in 6-7 year olds are described here. In children aged 13-14 years, the prevalence of asthma ever ranged from 5.5-28%, and the prevalence of wheezing in the last 12 months from 6.6-27%. In children aged 6-7 years, the prevalence of asthma ever ranged from 4.1-26.9%, and the prevalence of wheezing in the last 12 months ranged from 8.6-32.1%. The lower prevalence in centers with higher levels of atmospheric pollution suggests that chronic inhalation of polluted air in children does not contribute to asthma. Furthermore, the high figures for asthma in a region with a high level of gastrointestinal parasite infestation, and a high burden of acute respiratory infections occurring early in life, suggest that these factors, considered as protective in other regions, do not have the same effect in this region. The present study indicates that the prevalence of asthma and related symptoms in Latin America is as high and variable as described in industrialized or developed regions of the world. Pediatr Pulmonol. 2000; 30:439-444. (C) 2000 Wiley-Liss. Inc.. asthma| children| epidemiology| latin america| isaac| prevalence|children| australia| germany.	DEC-2000	asthma| children| epidemiology| latin america| isaac| prevalence|children| australia| germany	Mallol, J; Sole, D; Asher, I; Clayton, T; Stein, R; Soto-Quiroz, M	Prevalence of asthma symptoms in Latin America: The International Study of Asthma and Allergies in Childhood (ISAAC)		PEDIATRIC PULMONOLOGY	asthma; children; epidemiology; Latin America; ISAAC; prevalence	CHILDREN; AUSTRALIA; GERMANY	The prevalence of respiratory symptoms indicative of asthma in children from Latin America has been largely ignored. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), 17 centers in 9 different Latin American countries participated in the study, and data from 52,549 written questionnaires (WQ) in children aged 13-14 years and from 36,264 WQ in 6-7 year olds are described here. In children aged 13-14 years, the prevalence of asthma ever ranged from 5.5-28%, and the prevalence of wheezing in the last 12 months from 6.6-27%. In children aged 6-7 years, the prevalence of asthma ever ranged from 4.1-26.9%, and the prevalence of wheezing in the last 12 months ranged from 8.6-32.1%. The lower prevalence in centers with higher levels of atmospheric pollution suggests that chronic inhalation of polluted air in children does not contribute to asthma. Furthermore, the high figures for asthma in a region with a high level of gastrointestinal parasite infestation, and a high burden of acute respiratory infections occurring early in life, suggest that these factors, considered as protective in other regions, do not have the same effect in this region. The present study indicates that the prevalence of asthma and related symptoms in Latin America is as high and variable as described in industrialized or developed regions of the world. Pediatr Pulmonol. 2000; 30:439-444. (C) 2000 Wiley-Liss. Inc.	20	87	2000	6	10.1002/1099-0496(200012)30:6<439::AID-PPUL1>3.0.CO;2-E	Pediatrics; Respiratory System
Inhalation toxicology models of endotoxin- and bioaerosol-induced inflammation. Inhalation toxicology studies in rodents have proven their usefulness for furthering our understanding of the causal agents, mechanisms, and pathology associated with exposures to environmental endotoxins and bioaerosols. Inhalation animal models are used to determine which components of a mixture are the most important toxicants for inducing the observed adverse outcome. They are used to obtain exposure-response relationships for allergens and pro-inflammatory agents to help elucidate disease mechanisms and contribute quantitative data to the risk assessment process. Inhalation models serve as important adjuncts to epidemiology studies and human exposure studies. They are also useful for establishing phenotype in studies of genetic polymorphisms and disease susceptibility and are widely applied for evaluation of safety and efficacy for potential therapeutic agents. In order to produce reliable data, rigorous exposure chamber design, aerosol generation systems, exposure quantitation and experimental protocols must be utilized. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.. inhalation toxicology| exposure chambers| bioaerosols| endotoxin| glucans|pulmonary hypersensitivity responses| polymerase chain-reaction| murine model| guinea-pigs| cotton dust| rat nasal| (1->3)-beta-d-glucan| bacteria| system| hybridization.	NOV 2-2000	inhalation toxicology| exposure chambers| bioaerosols| endotoxin| glucans|pulmonary hypersensitivity responses| polymerase chain-reaction| murine model| guinea-pigs| cotton dust| rat nasal| (1->3)-beta-d-glucan| bacteria| system| hybridization	Thorne, PS	Inhalation toxicology models of endotoxin- and bioaerosol-induced inflammation		TOXICOLOGY	inhalation toxicology; exposure chambers; bioaerosols; endotoxin; glucans	PULMONARY HYPERSENSITIVITY RESPONSES; POLYMERASE CHAIN-REACTION; MURINE MODEL; GUINEA-PIGS; COTTON DUST; RAT NASAL; (1->3)-BETA-D-GLUCAN; BACTERIA; SYSTEM; HYBRIDIZATION	Inhalation toxicology studies in rodents have proven their usefulness for furthering our understanding of the causal agents, mechanisms, and pathology associated with exposures to environmental endotoxins and bioaerosols. Inhalation animal models are used to determine which components of a mixture are the most important toxicants for inducing the observed adverse outcome. They are used to obtain exposure-response relationships for allergens and pro-inflammatory agents to help elucidate disease mechanisms and contribute quantitative data to the risk assessment process. Inhalation models serve as important adjuncts to epidemiology studies and human exposure studies. They are also useful for establishing phenotype in studies of genetic polymorphisms and disease susceptibility and are widely applied for evaluation of safety and efficacy for potential therapeutic agents. In order to produce reliable data, rigorous exposure chamber design, aerosol generation systems, exposure quantitation and experimental protocols must be utilized. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.	47	87	2000	11	10.1016/S0300-483X(00)00287-0	Pharmacology & Pharmacy; Toxicology
Risk factors for community-acquired pneumonia diagnosed upon hospital admission. A case-control study of risk factors for community-acquired pneumonia in adults admitted to hospital is reported. Cases were surviving patients (n = 178) admitted to 14 hospitals in England. Controls were individuals (n = 385) randomly selected from the electoral registers of the areas served by the hospitals. The two groups were compared with regard to risk factors for pneumonia using a standardized postal questionnaire. Independent risk factors associated with cases in log-linear regression analysis were age, heart disease (as indicated by congestive heart Failure and/or digitalis treatment), lifetime smoking history, chronic airway disease (chronic bronchitis and/or asthma), occupational dust exposure, pneumonia as a child, single marital status and unemployment. Corticosteroid and bronchodilator therapy were also independent risk factors in the log-linear regression analysis, but may reflect the severity of underlying lung disease for which these drugs were prescribed. These data suggest that cigarette smoking is the major avoidable risk factor for acute pneumonia in adults.. case-control study| chronic obstructive pulmonary disease| congestive heart failure| epidemiology| occupational| pneumonia| risk factors| smoking|bacterial pneumonia| etiology| mortality| epidemiology| infection| smoking.	OCT-2000	case-control study| chronic obstructive pulmonary disease| congestive heart failure| epidemiology| occupational| pneumonia| risk factors| smoking|bacterial pneumonia| etiology| mortality| epidemiology| infection| smoking	Farr, BM; Bartlett, CLR; Wadsworth, J; Miller, DL	Risk factors for community-acquired pneumonia diagnosed upon hospital admission		RESPIRATORY MEDICINE	case-control study; chronic obstructive pulmonary disease; congestive heart failure; epidemiology; occupational; pneumonia; risk factors; smoking	BACTERIAL PNEUMONIA; ETIOLOGY; MORTALITY; EPIDEMIOLOGY; INFECTION; SMOKING	A case-control study of risk factors for community-acquired pneumonia in adults admitted to hospital is reported. Cases were surviving patients (n = 178) admitted to 14 hospitals in England. Controls were individuals (n = 385) randomly selected from the electoral registers of the areas served by the hospitals. The two groups were compared with regard to risk factors for pneumonia using a standardized postal questionnaire. Independent risk factors associated with cases in log-linear regression analysis were age, heart disease (as indicated by congestive heart Failure and/or digitalis treatment), lifetime smoking history, chronic airway disease (chronic bronchitis and/or asthma), occupational dust exposure, pneumonia as a child, single marital status and unemployment. Corticosteroid and bronchodilator therapy were also independent risk factors in the log-linear regression analysis, but may reflect the severity of underlying lung disease for which these drugs were prescribed. These data suggest that cigarette smoking is the major avoidable risk factor for acute pneumonia in adults.	45	87	2000	10	10.1053/rmed.2000.0865	Cardiovascular System & Cardiology; Respiratory System
Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness. Elevated serum Immunoglobulin E (IgE) levels and increased airway responsiveness (AR) are correlated traits that are characteristic of asthma. It is not known to what extent these traits arise from distinct or shared genetic determinants. We investigated the genetic and environmental components of variance of serum total and specific IgE levels and AR in an Australian population-based sample of 232 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits were also investigated. Log, total serum IgE levels had a narrow-sense heritability (h(N)(2)) of 47.3% (SE = 10.0%). Specific serum IgE levels against house dust mite and timothy grass, measured as a RAST Index, ad a h(N)(2) Of 33.8% (SE = 7.3%). AR, quantified by the log, dose-response slope to methacholine (DRS), had a h(N)(2) of 30.0% (SE = 12.3%). Extended modeling demonstrated an approximate 70% overlap in the genetic determinants of total and specific serum IgE levels. The genetic determinants of serum IgE levels and AR exhibited less than 30% sharing. These data are consistent with the existence of multiple genetic determinants of the pathophysiologic traits associated with asthma, and suggest that AR is genetically distinct from atopy. These results have implications for gene discovery programs.. skin-test reactivity| community population-sample| bronchial responsiveness| quantitative trait| general-population| asthma| ige| prevalence| atopy| twins.	JUN-2000	skin-test reactivity| community population-sample| bronchial responsiveness| quantitative trait| general-population| asthma| ige| prevalence| atopy| twins	Palmer, LJ; Burton, PR; Faux, JA; James, AL; Musk, AW; Cookson, WOCM	Independent inheritance of serum immunoglobulin E concentrations and airway responsiveness		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		SKIN-TEST REACTIVITY; COMMUNITY POPULATION-SAMPLE; BRONCHIAL RESPONSIVENESS; QUANTITATIVE TRAIT; GENERAL-POPULATION; ASTHMA; IGE; PREVALENCE; ATOPY; TWINS	Elevated serum Immunoglobulin E (IgE) levels and increased airway responsiveness (AR) are correlated traits that are characteristic of asthma. It is not known to what extent these traits arise from distinct or shared genetic determinants. We investigated the genetic and environmental components of variance of serum total and specific IgE levels and AR in an Australian population-based sample of 232 Caucasian nuclear families. The inter-relationships of the genetic determinants of these traits were also investigated. Log, total serum IgE levels had a narrow-sense heritability (h(N)(2)) of 47.3% (SE = 10.0%). Specific serum IgE levels against house dust mite and timothy grass, measured as a RAST Index, ad a h(N)(2) Of 33.8% (SE = 7.3%). AR, quantified by the log, dose-response slope to methacholine (DRS), had a h(N)(2) of 30.0% (SE = 12.3%). Extended modeling demonstrated an approximate 70% overlap in the genetic determinants of total and specific serum IgE levels. The genetic determinants of serum IgE levels and AR exhibited less than 30% sharing. These data are consistent with the existence of multiple genetic determinants of the pathophysiologic traits associated with asthma, and suggest that AR is genetically distinct from atopy. These results have implications for gene discovery programs.	35	87	2000	8		General & Internal Medicine; Respiratory System
Nevirapine versus Ritonavir-Boosted Lopinavir for HIV-Infected Children. BACKGROUND Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established. METHODS In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24. RESULTS A total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log(10) copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P < 0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P=0.04), as was the time to death (P=0.06). CONCLUSIONS Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.). single-dose nevirapine| randomized controlled-trial| antiretroviral therapy| protease inhibitor| drug-resistance| growth| initiation| dynamics| exposure| failure.	JUN 21-2012	single-dose nevirapine| randomized controlled-trial| antiretroviral therapy| protease inhibitor| drug-resistance| growth| initiation| dynamics| exposure| failure	Violari, A; Lindsey, JC; Hughes, MD; Mujuru, HA; Barlow-Mosha, L; Kamthunzi, P; Chi, BH; Cotton, MF; Moultrie, H; Khadse, S; Schimana, W; Bobat, R; Purdue, L; Eshleman, SH; Abrams, EJ; Millar, L; Petzold, E; Mofenson, LM; Jean-Philippe, P; Palumbo, P	Nevirapine versus Ritonavir-Boosted Lopinavir for HIV-Infected Children		NEW ENGLAND JOURNAL OF MEDICINE		SINGLE-DOSE NEVIRAPINE; RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITOR; DRUG-RESISTANCE; GROWTH; INITIATION; DYNAMICS; EXPOSURE; FAILURE	BACKGROUND Nevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established. METHODS In a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24. RESULTS A total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log(10) copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P < 0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P=0.04), as was the time to death (P=0.06). CONCLUSIONS Outcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.)	16	86	2012	10		General & Internal Medicine
Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome. Background: Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), are life-threatening drug hypersensitivities with robust immune responses to drugs. Despite the strong HLA predisposition to drug hypersensitivities, such as HLA-B*1502 to carbamazepine (CBZ)-induced SJS/TEN, it remains unknown whether particular T-cell receptors (TCRs) participate in recognition of small drug/peptide-HLA complexes. Objective: Using the strong HLA predisposition in patients with CBZ-induced SJS/TEN as a model, we aimed to study the use of TCR repertoire in patients with drug hypersensitivity. Method: We enrolled patients with CBZ-SJS/TEN, tolerant control subjects, and healthy subjects who had no history of CBZ exposure. We isolated PBMCs from the subjects, cultured CBZ-specific T cells, and globally investigated the expression level and third complementarity-determining region length distribution of the TCR profile. We further assessed the pathogenic role of the disease-specific clonotype using real-time PCR-based tests and functional analysis. Results: On drug stimulation, CBZ-specific CD8(+) T cells were expanded in vitro and activated to release granulysin. Notably, VB-11-ISGSY was identified as the most predominant clonotype and shared among different subjects. This clonotype was present in 16 (84%) of 19 patients with SJS/TEN, absent in all 17 tolerant patients, and present at a low frequency in healthy subjects (4/29 [14%]). CBZ-specific cytotoxicity could be primed in vitro in the PBMCs of healthy subjects who are carriers of HLA-B*1502 and VB-11-ISGSY; this cytotoxicity could be blocked by an anti-TCR-VB-11 antibody. Furthermore, a single T-cell clone expressing VA-22-FISGTY/VB-11-ISGSY showed significant cytotoxicity against HLA-B*1502-positive antigen-presenting cells and CBZ. Conclusion: This study establishes the key role of the TCR in the pathogenic mechanism of SJS/TEN, explains why some HLA-B*1502 carriers are tolerant to CBZ, and provides a biomarker profile for drug hypersensitivity. (J Allergy Clin Immunol 2011;128:1266-76.). drug hypersensitivity| t-cell receptor| hla| third complementarity-determining region| stevens-johnson syndrome| toxic epidermal necrolysis|toxic epidermal necrolysis| hla-b-asterisk-1502 allele| drug hypersensitivity| liver-injury| han chinese| oxcarbazepine| risk| association| activation| clones.	DEC-2011	drug hypersensitivity| t-cell receptor| hla| third complementarity-determining region| stevens-johnson syndrome| toxic epidermal necrolysis|toxic epidermal necrolysis| hla-b-asterisk-1502 allele| drug hypersensitivity| liver-injury| han chinese| oxcarbazepine| risk| association| activation| clones	Ko, TM; Chung, WH; Wei, CY; Shih, HY; Chen, JK; Lin, CH; Chen, YT; Hung, SI	Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Drug hypersensitivity; T-cell receptor; HLA; third complementarity-determining region; Stevens-Johnson syndrome; toxic epidermal necrolysis	TOXIC EPIDERMAL NECROLYSIS; HLA-B-ASTERISK-1502 ALLELE; DRUG HYPERSENSITIVITY; LIVER-INJURY; HAN CHINESE; OXCARBAZEPINE; RISK; ASSOCIATION; ACTIVATION; CLONES	Background: Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), are life-threatening drug hypersensitivities with robust immune responses to drugs. Despite the strong HLA predisposition to drug hypersensitivities, such as HLA-B*1502 to carbamazepine (CBZ)-induced SJS/TEN, it remains unknown whether particular T-cell receptors (TCRs) participate in recognition of small drug/peptide-HLA complexes. Objective: Using the strong HLA predisposition in patients with CBZ-induced SJS/TEN as a model, we aimed to study the use of TCR repertoire in patients with drug hypersensitivity. Method: We enrolled patients with CBZ-SJS/TEN, tolerant control subjects, and healthy subjects who had no history of CBZ exposure. We isolated PBMCs from the subjects, cultured CBZ-specific T cells, and globally investigated the expression level and third complementarity-determining region length distribution of the TCR profile. We further assessed the pathogenic role of the disease-specific clonotype using real-time PCR-based tests and functional analysis. Results: On drug stimulation, CBZ-specific CD8(+) T cells were expanded in vitro and activated to release granulysin. Notably, VB-11-ISGSY was identified as the most predominant clonotype and shared among different subjects. This clonotype was present in 16 (84%) of 19 patients with SJS/TEN, absent in all 17 tolerant patients, and present at a low frequency in healthy subjects (4/29 [14%]). CBZ-specific cytotoxicity could be primed in vitro in the PBMCs of healthy subjects who are carriers of HLA-B*1502 and VB-11-ISGSY; this cytotoxicity could be blocked by an anti-TCR-VB-11 antibody. Furthermore, a single T-cell clone expressing VA-22-FISGTY/VB-11-ISGSY showed significant cytotoxicity against HLA-B*1502-positive antigen-presenting cells and CBZ. Conclusion: This study establishes the key role of the TCR in the pathogenic mechanism of SJS/TEN, explains why some HLA-B*1502 carriers are tolerant to CBZ, and provides a biomarker profile for drug hypersensitivity. (J Allergy Clin Immunol 2011;128:1266-76.)	40	86	2011	22	10.1016/j.jaci.2011.08.013	Allergy; Immunology
Atopy Risk in Infants and Children in Relation to Early Exposure to Fish, Oily Fish, or Long-Chain Omega-3 Fatty Acids: A Systematic Review. There are two main families of polyunsaturated fatty acids (PUFAs), the n-6 and the n-3 families. It has been suggested that there is a causal relationship between n-6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n-6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n-3 PUFAs and these fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n-3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n-3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.. atopy| allergy| asthma| eczema| immune function| inflammation| eicosanoid| cytokine| fatty acid| fish oil| pregnancy|fatty-acid-composition| randomized controlled-trial| childhood asthma prevention| allergic rhinitis| dietary factors| cord-blood| eicosapentaenoic acid| docosahexaenoic acid| airway inflammation| cytokine production.	AUG-2011	atopy| allergy| asthma| eczema| immune function| inflammation| eicosanoid| cytokine| fatty acid| fish oil| pregnancy|fatty-acid-composition| randomized controlled-trial| childhood asthma prevention| allergic rhinitis| dietary factors| cord-blood| eicosapentaenoic acid| docosahexaenoic acid| airway inflammation| cytokine production	Kremmyda, LS; Vlachava, M; Noakes, PS; Diaper, ND; Miles, EA; Calder, PC	Atopy Risk in Infants and Children in Relation to Early Exposure to Fish, Oily Fish, or Long-Chain Omega-3 Fatty Acids: A Systematic Review		CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY	Atopy; Allergy; Asthma; Eczema; Immune function; Inflammation; Eicosanoid; Cytokine; Fatty acid; Fish oil; Pregnancy	FATTY-ACID-COMPOSITION; RANDOMIZED CONTROLLED-TRIAL; CHILDHOOD ASTHMA PREVENTION; ALLERGIC RHINITIS; DIETARY FACTORS; CORD-BLOOD; EICOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID; AIRWAY INFLAMMATION; CYTOKINE PRODUCTION	There are two main families of polyunsaturated fatty acids (PUFAs), the n-6 and the n-3 families. It has been suggested that there is a causal relationship between n-6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n-6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n-3 PUFAs and these fatty acids act to oppose the actions of n-6 PUFAs. Thus, it is considered that n-3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n-3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n-3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.	73	86	2011	31	10.1007/s12016-009-8186-2	Allergy; Immunology
Imaging of Lung Function Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: Review of Current and Emerging Translational Methods and Applications. During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma chronic obstructive pulmonary disease cystic fibrosis radiation-induced lung injury and transplantation This review focuses on the state-of-the-art of HP 3He MRI and its application to clinical pulmonary research This is not an overview of the physics of the method as this topic has been covered previously We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical research and decision making in pulmonary medicine Particular attention is given to functional imaging approaches related to ventilation and diffusion-weighted imaging with applications in chronic obstructive pulmonary disease cystic fibrosis, asthma and radiation-induced lung injury The strengths and challenges of the application of 3He MRI in these indications are discussed along with a comparison to established and emerging imaging techniques. pulmonary mri| hyperpolarized noble gas| (3)he mri| copd| cystic fibrosis asthma|apparent diffusion-coefficient| long-range diffusion| oxygen-sensitive he-3-mri| air-flow obstruction| quantitative assessment| projection acquisition| ventilation defects| pulmonary-function| multidetector ct| collateral paths.	DEC-2010	pulmonary mri| hyperpolarized noble gas| (3)he mri| copd| cystic fibrosis asthma|apparent diffusion-coefficient| long-range diffusion| oxygen-sensitive he-3-mri| air-flow obstruction| quantitative assessment| projection acquisition| ventilation defects| pulmonary-function| multidetector ct| collateral paths	Fain, S; Schiebler, ML; McCormack, DG; Parraga, G	Imaging of Lung Function Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: Review of Current and Emerging Translational Methods and Applications		JOURNAL OF MAGNETIC RESONANCE IMAGING	pulmonary MRI; hyperpolarized noble gas; (3)He MRI; COPD; cystic fibrosis asthma	APPARENT DIFFUSION-COEFFICIENT; LONG-RANGE DIFFUSION; OXYGEN-SENSITIVE HE-3-MRI; AIR-FLOW OBSTRUCTION; QUANTITATIVE ASSESSMENT; PROJECTION ACQUISITION; VENTILATION DEFECTS; PULMONARY-FUNCTION; MULTIDETECTOR CT; COLLATERAL PATHS	During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma chronic obstructive pulmonary disease cystic fibrosis radiation-induced lung injury and transplantation This review focuses on the state-of-the-art of HP 3He MRI and its application to clinical pulmonary research This is not an overview of the physics of the method as this topic has been covered previously We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical research and decision making in pulmonary medicine Particular attention is given to functional imaging approaches related to ventilation and diffusion-weighted imaging with applications in chronic obstructive pulmonary disease cystic fibrosis, asthma and radiation-induced lung injury The strengths and challenges of the application of 3He MRI in these indications are discussed along with a comparison to established and emerging imaging techniques	104	86	2010	11	10.1002/jmri.22375	Radiology, Nuclear Medicine & Medical Imaging
Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. Background: Although specific immunotherapy is a valuable treatment option for patients with allergic asthma, the potential for systemic allergic reactions has limited its use, especially for patients with symptomatic disease. Objective: To evaluate omalizumab's effect on the tolerability of specific immunotherapy in patients with symptomatic persistent asthma not adequately controlled with inhaled corticosteroids. Methods: This multicenter, double-blind, parallel-group study randomized patients to treatment with omalizumab or placebo, after which they received specific immunotherapy to at least I of 3 perennial aeroallergens (cat, dog, and house dust mite) according to a 4-week, 18-injection cluster regimen, followed by 7 weeks of maintenance therapy. The primary efficacy variable, a systemic allergic reaction after immunotherapy, was analyzed by using the Cochrane-Mantel-Haenszel test. Results: A total of 248 randomized patients (126 omalizumab, 122 placebo) received at least I dose of immunotherapy and were evaluated for efficacy. Patients receiving omalizumab experienced significantly fewer systemic allergic reactions to immunotherapy than those receiving placebo (17/126 [13.5%] vs 32/122 [26.2%]; P = .017; 95% CI, 2.91% to 22.56%) and had fewer respiratory-related (grade 3) systemic allergic reactions (6 vs 24, respectively). Grade 4 reactions were reported in 2 patients in each group. More omalizumab patients were able to reach the target maintenance immunotherapy dose (110 [87.3%] vs 88 [72.1%], respectively; P = .004). Conclusion: Use of omalizumab in patients whose asthma was symptomatic despite use of inhaled corticosteroids was associated with fewer systemic allergic reactions to specific immunotherapy and enabled more patients to achieve the target immunotherapy maintenance dose. (J Allergy, Clin Immunol 2010; 125:383-9.). omalizumab| allergic asthma| immunotherapy| systemic allergic reactions| cluster immunotherapy| cat| dog| house dust mines|anti-ige antibody| ri expression| double-blind| rhinitis| children.	FEB-2010	omalizumab| allergic asthma| immunotherapy| systemic allergic reactions| cluster immunotherapy| cat| dog| house dust mines|anti-ige antibody| ri expression| double-blind| rhinitis| children	Massanari, M; Nelson, H; Casale, T; Busse, W; Kianifard, F; Geba, GP; Zeldin, RK	Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Omalizumab; allergic asthma; immunotherapy; systemic allergic reactions; cluster immunotherapy; cat; dog; house dust mines	ANTI-IGE ANTIBODY; RI EXPRESSION; DOUBLE-BLIND; RHINITIS; CHILDREN	Background: Although specific immunotherapy is a valuable treatment option for patients with allergic asthma, the potential for systemic allergic reactions has limited its use, especially for patients with symptomatic disease. Objective: To evaluate omalizumab's effect on the tolerability of specific immunotherapy in patients with symptomatic persistent asthma not adequately controlled with inhaled corticosteroids. Methods: This multicenter, double-blind, parallel-group study randomized patients to treatment with omalizumab or placebo, after which they received specific immunotherapy to at least I of 3 perennial aeroallergens (cat, dog, and house dust mite) according to a 4-week, 18-injection cluster regimen, followed by 7 weeks of maintenance therapy. The primary efficacy variable, a systemic allergic reaction after immunotherapy, was analyzed by using the Cochrane-Mantel-Haenszel test. Results: A total of 248 randomized patients (126 omalizumab, 122 placebo) received at least I dose of immunotherapy and were evaluated for efficacy. Patients receiving omalizumab experienced significantly fewer systemic allergic reactions to immunotherapy than those receiving placebo (17/126 [13.5%] vs 32/122 [26.2%]; P = .017; 95% CI, 2.91% to 22.56%) and had fewer respiratory-related (grade 3) systemic allergic reactions (6 vs 24, respectively). Grade 4 reactions were reported in 2 patients in each group. More omalizumab patients were able to reach the target maintenance immunotherapy dose (110 [87.3%] vs 88 [72.1%], respectively; P = .004). Conclusion: Use of omalizumab in patients whose asthma was symptomatic despite use of inhaled corticosteroids was associated with fewer systemic allergic reactions to specific immunotherapy and enabled more patients to achieve the target immunotherapy maintenance dose. (J Allergy, Clin Immunol 2010; 125:383-9.)	22	86	2010	7	10.1016/j.jaci.2009.11.022	Allergy; Immunology
The importance of nurse-led home visits in the assessment of children with problematic asthma. Objective: To evaluate and identify potentially modifiable factors in children with problematic asthma by a nurse-led assessment and home visit. Design: Observational cohort study. Setting: A tertiary paediatric respiratory centre. Patients: 71 children, aged 4.5-17.5 years, with problematic asthma currently under follow-up at a tertiary respiratory centre. Interventions: A nurse-led hospital visit followed by a home visit. Main outcome measures: Identification and attempted change of exacerbating factors so that further investigations and consideration of off-label, potentially toxic, asthma therapies were not necessary. Results: Potentially modifiable factors were identified in 56 (79%) children. Many children had multiple causes for poor control. The most important were ongoing allergen exposure, 22 children (31%); passive or active smoking, 18 children (25%); medication issues including adherence, 34 children (48%); psychosocial factors, 42 families (59%). The home visit contributed valuable information to this assessment. At the home visit house dust mite avoidance measures were found to be inadequate in 84% of those sensitised; medications were not easily available for inspection or were out of date in 23%; 74% of psychology referrals were made after the home visit. In 39 children (55%) the factors identified and the interventions recommended meant that further escalation of treatment was avoided. Conclusions: Nurse-led assessments including a home visit can help identify potentially modifiable factors for poorly controlled symptoms in children with problematic asthma.. quality-of-life| difficult asthma| risk-factors| intervention| severity| doctor| costs.	OCT-2009	quality-of-life| difficult asthma| risk-factors| intervention| severity| doctor| costs	Bracken, M; Fleming, L; Hall, P; Van Stiphout, N; Bossley, C; Biggart, E; Wilson, NM; Bush, A	The importance of nurse-led home visits in the assessment of children with problematic asthma		ARCHIVES OF DISEASE IN CHILDHOOD		QUALITY-OF-LIFE; DIFFICULT ASTHMA; RISK-FACTORS; INTERVENTION; SEVERITY; DOCTOR; COSTS	Objective: To evaluate and identify potentially modifiable factors in children with problematic asthma by a nurse-led assessment and home visit. Design: Observational cohort study. Setting: A tertiary paediatric respiratory centre. Patients: 71 children, aged 4.5-17.5 years, with problematic asthma currently under follow-up at a tertiary respiratory centre. Interventions: A nurse-led hospital visit followed by a home visit. Main outcome measures: Identification and attempted change of exacerbating factors so that further investigations and consideration of off-label, potentially toxic, asthma therapies were not necessary. Results: Potentially modifiable factors were identified in 56 (79%) children. Many children had multiple causes for poor control. The most important were ongoing allergen exposure, 22 children (31%); passive or active smoking, 18 children (25%); medication issues including adherence, 34 children (48%); psychosocial factors, 42 families (59%). The home visit contributed valuable information to this assessment. At the home visit house dust mite avoidance measures were found to be inadequate in 84% of those sensitised; medications were not easily available for inspection or were out of date in 23%; 74% of psychology referrals were made after the home visit. In 39 children (55%) the factors identified and the interventions recommended meant that further escalation of treatment was avoided. Conclusions: Nurse-led assessments including a home visit can help identify potentially modifiable factors for poorly controlled symptoms in children with problematic asthma.	25	86	2009	5	10.1136/adc.2008.152140	Pediatrics
The European baseline series in 10 European Countries, 2005/2006-Results of the European Surveillance System on Contact Allergies (ESSCA). Background Continual surveillance based on patch test results has proved useful for the identification of contact allergy. Objectives To provide a current view on the spectrum of contact allergy to important sensitizers across Europe. Patients/Methods Clinical and patch test data of 19 793 patients patch tested in 2005/2006 in the 31 participating departments from 10 European countries (the European Surveillance System on Contact Allergies' (ESSCA) www.essca-dc.org) were descriptively analysed, aggregated to four European regions. Results Nickel sulfate remains the most common allergen with standardized prevalences ranging from 19.7% (central Europe) to 24.4% (southern Europe). While a number of allergens shows limited variation across the four regions, such as Myroxylon pereirae (5.3-6.8%), cobalt chloride (6.2-8.8%) or thiuram mix (1.7-2.4%), the differences observed with other allergens may hint on underlying differences in exposures, for example: dichromate 2.4% in the UK (west) versus 4.5-5.9% in the remaining EU regions, methylchloroisothiazolinone/methylisothiazolinone 4.1% in the South versus 2.1-2.7% in the remaining regions. Conclusions Notwithstanding residual methodological variation (affecting at least some 'difficult' allergens) tackled by ongoing efforts for standardization, a comparative analysis as presented provides (i) a broad overview on contact allergy frequencies and (ii) interesting starting points for further, in-depth investigation.. clinical epidemiology| contact allergy| patch testing|patch test series| multifactorial analysis| methyldibromo glutaronitrile| tixocortol pivalate| standard series| recommendation| multicenter| frequency| age.	2009	clinical epidemiology| contact allergy| patch testing|patch test series| multifactorial analysis| methyldibromo glutaronitrile| tixocortol pivalate| standard series| recommendation| multicenter| frequency| age	Uter, W; Ramsch, C; Aberer, W; Ayala, F; Balato, A; Beliauskiene, A; Fortina, AB; Bircher, A; Brasch, J; Chowdhury, MMU; Coenraads, PJ; Schuttelaar, ML; Cooper, S; Corradin, MT; Elsner, P; English, JSC; Fartasch, M; Mahler, V; Frosch, PJ; Fuchs, T; Gawkrodger, DJ; Gimenez-Arnau, AM; Green, CM; Horne, HL; Jolanki, R; King, CM; Krecisz, B; Kiec-Swierczynska, M; Ormerod, AD; Orton, DI; Peserico, A; Rantanen, T; Rustemeyer, T; Sansom, JE; Simon, D; Statham, BN; Wilkinson, M; Schnuch, A	The European baseline series in 10 European Countries, 2005/2006-Results of the European Surveillance System on Contact Allergies (ESSCA)		CONTACT DERMATITIS	clinical epidemiology; contact allergy; patch testing	PATCH TEST SERIES; MULTIFACTORIAL ANALYSIS; METHYLDIBROMO GLUTARONITRILE; TIXOCORTOL PIVALATE; STANDARD SERIES; RECOMMENDATION; MULTICENTER; FREQUENCY; AGE	Background Continual surveillance based on patch test results has proved useful for the identification of contact allergy. Objectives To provide a current view on the spectrum of contact allergy to important sensitizers across Europe. Patients/Methods Clinical and patch test data of 19 793 patients patch tested in 2005/2006 in the 31 participating departments from 10 European countries (the European Surveillance System on Contact Allergies' (ESSCA) www.essca-dc.org) were descriptively analysed, aggregated to four European regions. Results Nickel sulfate remains the most common allergen with standardized prevalences ranging from 19.7% (central Europe) to 24.4% (southern Europe). While a number of allergens shows limited variation across the four regions, such as Myroxylon pereirae (5.3-6.8%), cobalt chloride (6.2-8.8%) or thiuram mix (1.7-2.4%), the differences observed with other allergens may hint on underlying differences in exposures, for example: dichromate 2.4% in the UK (west) versus 4.5-5.9% in the remaining EU regions, methylchloroisothiazolinone/methylisothiazolinone 4.1% in the South versus 2.1-2.7% in the remaining regions. Conclusions Notwithstanding residual methodological variation (affecting at least some 'difficult' allergens) tackled by ongoing efforts for standardization, a comparative analysis as presented provides (i) a broad overview on contact allergy frequencies and (ii) interesting starting points for further, in-depth investigation.	20	86	2009	8		Allergy; Dermatology
Living on a farm: Impact on asthma induction and clinical course. Exposure to a farming environment protects individuals from respiratory allergy The timing and duration of exposure seem to play critical roles. The largest reduction in risk of developing respiratory allergies is seen among those who are exposed prenatally and continuously thereafter. Contact with farm animals, at least in childhood, likely confers protection; other factors have not been completely identified. Also, the consumption of milk directly from the farm during childhood has been shown to be beneficial with respect to childhood asthma and allergies. Increased levels of microbial substances may contribute to the protective effects. The mechanisms by which such environmental exposures confer protection from respiratory allergies are not well understood. A number of gene-by-environment interactions have been observed with polymorphisms in genes of innate immunity receptors and exposure to farming environments. Increased levels of microbial exposures recognized by innate immune responses may affect adaptive immune responses resulting in decreased levels of atopic sensitization and asthma.. community respiratory health| young danish farmers| toll-like receptor-2| school-age-children| atopic sensitization| allergic diseases| inverse association| hay-fever| european farmers| nonatopic asthma.	AUG-2008	community respiratory health| young danish farmers| toll-like receptor-2| school-age-children| atopic sensitization| allergic diseases| inverse association| hay-fever| european farmers| nonatopic asthma	von Mutius, E; Radon, K	Living on a farm: Impact on asthma induction and clinical course		IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA		COMMUNITY RESPIRATORY HEALTH; YOUNG DANISH FARMERS; TOLL-LIKE RECEPTOR-2; SCHOOL-AGE-CHILDREN; ATOPIC SENSITIZATION; ALLERGIC DISEASES; INVERSE ASSOCIATION; HAY-FEVER; EUROPEAN FARMERS; NONATOPIC ASTHMA	Exposure to a farming environment protects individuals from respiratory allergy The timing and duration of exposure seem to play critical roles. The largest reduction in risk of developing respiratory allergies is seen among those who are exposed prenatally and continuously thereafter. Contact with farm animals, at least in childhood, likely confers protection; other factors have not been completely identified. Also, the consumption of milk directly from the farm during childhood has been shown to be beneficial with respect to childhood asthma and allergies. Increased levels of microbial substances may contribute to the protective effects. The mechanisms by which such environmental exposures confer protection from respiratory allergies are not well understood. A number of gene-by-environment interactions have been observed with polymorphisms in genes of innate immunity receptors and exposure to farming environments. Increased levels of microbial exposures recognized by innate immune responses may affect adaptive immune responses resulting in decreased levels of atopic sensitization and asthma.	73	86	2008	19	10.1016/j.iac.2008.03.010	Allergy; Immunology
Exposure to multiple indoor allergens in US homes and its relationship to asthma. Background: The National Survey of Lead and Allergens in Housing was the first population-based study to measure indoor allergen levels in US homes. Objective: We characterized the overall burden to multiple allergens and examined whether increased allergen levels were associated with occupants' asthma status. Methods: This cross-sectional study surveyed a nationally representative sample of 831 housing units in 75 different locations throughout the United States. Information was collected by means of questionnaire and environmental assessment. Allergen concentrations in dust samples were assessed by using immunoassays. The following cutoff points were used to define increased allergen levels: 10 mu g/g for Der p 1, Der f 1, and Can f 1; 8 mu g/g for Fel d 1; 8 U/g for Bla g 1; 1.6 mu g/g for mouse urinary protein; and 7 mu g/g for Alternaria alternata antigens. Allergen burden was considered high when 4 or more allergens exceeded increased levels in any of the sampling locations. Results: Exposure to multiple allergens was common in US homes. Of the surveyed homes, 51.5% had at least 6 detectable allergens and 45.8% had at least 3 allergens exceeding increased levels. Race, income, housing type, absence of children, and presence of smokers, pets, cockroaches, rodents, and mold/moisture-related problems were independent predictors of high allergen burden. Among atopic subjects, high allergen burden increased the odds of having asthma symptoms (odds ratio, 1.81; 95% CI, 1.04-3.15). Conclusion: Increased allergen levels in the home are associated with asthma symptoms in allergic individuals.. allergen| indoor exposure| asthma| allergy|house-dust mite| inner-city children| 1st national-survey| alternaria-alternata| mouse allergen| environmental intervention| cockroach allergen| united-states| dog allergen| sensitization.	MAR-2008	allergen| indoor exposure| asthma| allergy|house-dust mite| inner-city children| 1st national-survey| alternaria-alternata| mouse allergen| environmental intervention| cockroach allergen| united-states| dog allergen| sensitization	Salo, PM; Arbes, SJ; Crockett, PW; Thorne, PS; Cohn, RD; Zeldin, DC	Exposure to multiple indoor allergens in US homes and its relationship to asthma		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergen; indoor exposure; asthma; allergy	HOUSE-DUST MITE; INNER-CITY CHILDREN; 1ST NATIONAL-SURVEY; ALTERNARIA-ALTERNATA; MOUSE ALLERGEN; ENVIRONMENTAL INTERVENTION; COCKROACH ALLERGEN; UNITED-STATES; DOG ALLERGEN; SENSITIZATION	Background: The National Survey of Lead and Allergens in Housing was the first population-based study to measure indoor allergen levels in US homes. Objective: We characterized the overall burden to multiple allergens and examined whether increased allergen levels were associated with occupants' asthma status. Methods: This cross-sectional study surveyed a nationally representative sample of 831 housing units in 75 different locations throughout the United States. Information was collected by means of questionnaire and environmental assessment. Allergen concentrations in dust samples were assessed by using immunoassays. The following cutoff points were used to define increased allergen levels: 10 mu g/g for Der p 1, Der f 1, and Can f 1; 8 mu g/g for Fel d 1; 8 U/g for Bla g 1; 1.6 mu g/g for mouse urinary protein; and 7 mu g/g for Alternaria alternata antigens. Allergen burden was considered high when 4 or more allergens exceeded increased levels in any of the sampling locations. Results: Exposure to multiple allergens was common in US homes. Of the surveyed homes, 51.5% had at least 6 detectable allergens and 45.8% had at least 3 allergens exceeding increased levels. Race, income, housing type, absence of children, and presence of smokers, pets, cockroaches, rodents, and mold/moisture-related problems were independent predictors of high allergen burden. Among atopic subjects, high allergen burden increased the odds of having asthma symptoms (odds ratio, 1.81; 95% CI, 1.04-3.15). Conclusion: Increased allergen levels in the home are associated with asthma symptoms in allergic individuals.	39	86	2008	7	10.1016/j.jaci.2007.12.1164	Allergy; Immunology
Air pollution from biomass burning and asthma hospital admissions in a sugar cane plantation area in Brazil. Objective: To evaluate the association between the total suspended particles (TSPs) generated from preharvest sugar cane burning and hospital admission due to asthma ( asthma hospital admissions) in the city of Araraquara. Design: An ecological time-series study. Total daily records of asthma hospital admissions (ICD 10th J15) were obtained from one of the main hospitals in Araraquara, Sao Paulo State, Brazil, from 23 March 2003 to 27 July 2004. The daily concentration of TSP (mu g/m(3)) was obtained using Handi-vol equipment (Energetica, Brazil) placed in downtown Araraquara. The local airport provided the daily mean figures of temperature and humidity. The daily number of asthma hospital admissions was considered as the dependent variable in Poisson's regression models and the daily concentration of TSP was considered the independent variable. The generalised linear model with natural cubic spline was adopted to control for long-time trend. Linear terms were used for weather variables. Results: TSP had an acute effect on asthma admissions, starting 1 day after TSP concentrations increased and remaining almost unchanged for the next four days. A 10 mu g/m(3) increase in the 5-day moving average (lag1-5) of TSP concentrations was associated with an increase of 11.6% (95% CI 5.4 to 17.7) in asthma hospital admissions. Conclusion: Increases in TSP concentrations were definitely associated with asthma hospital admissions in Araraquara and, despite using sugar cane alcohol to reduce air pollution from automotive sources in large Brazilian urban centres, the cities where sugar cane is harvested pay a high toll in terms of public health.. emergency-room visits| cytokine production| children| population| california| symptoms| exposure| seattle| haze| utah.	MAY-2007	emergency-room visits| cytokine production| children| population| california| symptoms| exposure| seattle| haze| utah	Arbex, MA; Martins, LC; de Oliveira, RC; Pereira, LAA; Arbex, FF; Cancado, JED; Saldiva, PHN; Braga, ALF	Air pollution from biomass burning and asthma hospital admissions in a sugar cane plantation area in Brazil		JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH		EMERGENCY-ROOM VISITS; CYTOKINE PRODUCTION; CHILDREN; POPULATION; CALIFORNIA; SYMPTOMS; EXPOSURE; SEATTLE; HAZE; UTAH	Objective: To evaluate the association between the total suspended particles (TSPs) generated from preharvest sugar cane burning and hospital admission due to asthma ( asthma hospital admissions) in the city of Araraquara. Design: An ecological time-series study. Total daily records of asthma hospital admissions (ICD 10th J15) were obtained from one of the main hospitals in Araraquara, Sao Paulo State, Brazil, from 23 March 2003 to 27 July 2004. The daily concentration of TSP (mu g/m(3)) was obtained using Handi-vol equipment (Energetica, Brazil) placed in downtown Araraquara. The local airport provided the daily mean figures of temperature and humidity. The daily number of asthma hospital admissions was considered as the dependent variable in Poisson's regression models and the daily concentration of TSP was considered the independent variable. The generalised linear model with natural cubic spline was adopted to control for long-time trend. Linear terms were used for weather variables. Results: TSP had an acute effect on asthma admissions, starting 1 day after TSP concentrations increased and remaining almost unchanged for the next four days. A 10 mu g/m(3) increase in the 5-day moving average (lag1-5) of TSP concentrations was associated with an increase of 11.6% (95% CI 5.4 to 17.7) in asthma hospital admissions. Conclusion: Increases in TSP concentrations were definitely associated with asthma hospital admissions in Araraquara and, despite using sugar cane alcohol to reduce air pollution from automotive sources in large Brazilian urban centres, the cities where sugar cane is harvested pay a high toll in terms of public health.	45	86	2007	6	10.1136/jech.2005.044743	Public, Environmental & Occupational Health
Triggers of IgE class switching and allergy development. The prevalence of immunoglobulin E (IgE)-mediated allergic diseases has been increasing for the last four decades. In this review determinants for an increased IgE synthesis are discussed on both an epidemiological and on an immunological level with special emphasis on the differentiation of the B cell to an IgE-producing plasma cell. Factors that favor an IgE immune response are low antigen doses and immunization via mucous membranes, but it is highly likely that other environmental factors besides exposure to the allergenic sources play a role. Important factors in the formation of the Thelper type 2 (Th2) T cell subset are the actions of thymic stromal lymphopoietin (TSLP) on dendritic cells and the OX40 ligand on CD4+ T cells. In order for a B lymphocyte to switch to IgE production it needs two signals provided by a Th2 cell in the form of the cytokines interleukin (IL-) 4/IL-13 and ligation of the CD40. In spite of a half-life of only a few days, there is evidence that the IgE response may last for years even without allergen stimulation. This is likely to be caused by long-lived IgE-producing plasma cells, and such cells may be difficult to target therapeutically thus emphasizing the need for more knowledge on preventable causes of IgE- and allergy development.. allergy| asthma| b lymphocytes| class switch recombination| ige| ox40 ligand| th2 lymphocytes| tslp|human b-cells| single-stranded-dna| anti-cd40 monoclonal-antibodies| immunoglobulin-secreting cells| epsilon germline transcripts| cytidine deaminase aid| regulatory t-cells| total serum ige| plasma-cell| ifn-gamma.	2007	allergy| asthma| b lymphocytes| class switch recombination| ige| ox40 ligand| th2 lymphocytes| tslp|human b-cells| single-stranded-dna| anti-cd40 monoclonal-antibodies| immunoglobulin-secreting cells| epsilon germline transcripts| cytidine deaminase aid| regulatory t-cells| total serum ige| plasma-cell| ifn-gamma	Poulsen, LK; Hummelshoj, L	Triggers of IgE class switching and allergy development		ANNALS OF MEDICINE	allergy; asthma; B lymphocytes; class switch recombination; IgE; OX40 ligand; Th2 lymphocytes; TSLP	HUMAN B-CELLS; SINGLE-STRANDED-DNA; ANTI-CD40 MONOCLONAL-ANTIBODIES; IMMUNOGLOBULIN-SECRETING CELLS; EPSILON GERMLINE TRANSCRIPTS; CYTIDINE DEAMINASE AID; REGULATORY T-CELLS; TOTAL SERUM IGE; PLASMA-CELL; IFN-GAMMA	The prevalence of immunoglobulin E (IgE)-mediated allergic diseases has been increasing for the last four decades. In this review determinants for an increased IgE synthesis are discussed on both an epidemiological and on an immunological level with special emphasis on the differentiation of the B cell to an IgE-producing plasma cell. Factors that favor an IgE immune response are low antigen doses and immunization via mucous membranes, but it is highly likely that other environmental factors besides exposure to the allergenic sources play a role. Important factors in the formation of the Thelper type 2 (Th2) T cell subset are the actions of thymic stromal lymphopoietin (TSLP) on dendritic cells and the OX40 ligand on CD4+ T cells. In order for a B lymphocyte to switch to IgE production it needs two signals provided by a Th2 cell in the form of the cytokines interleukin (IL-) 4/IL-13 and ligation of the CD40. In spite of a half-life of only a few days, there is evidence that the IgE response may last for years even without allergen stimulation. This is likely to be caused by long-lived IgE-producing plasma cells, and such cells may be difficult to target therapeutically thus emphasizing the need for more knowledge on preventable causes of IgE- and allergy development.	159	86	2007	17	10.1080/07853890701449354	General & Internal Medicine
Environmental hazards: Evidence for effects on child health. The human fetus, child, and adult may experience adverse health outcomes from parental or childhood exposures to environmental toxicants. The fetus and infant are especially vulnerable to toxicants that disrupt developmental processes during relatively narrow time windows. This review summarizes knowledge of associations between child health and development outcomes and environmental exposures, including lead, methylmercury, polychlorinated biphenyls (PCBs), dioxins and related polyhalogenated aromatic hydrocarbons (PHAHs), certain pesticides, environmental tobacco smoke (ETS), aeroallergens, ambient air toxicants (especially particulate matter [PM] and ozone), chlorination disinfection by-products (DBPs), sunlight, power-frequency magnetic fields, radiofrequency (RF) radiation, residential proximity to hazardous waste disposal sites, and solvents. The adverse health effects linked to such exposures include fetal death, birth defects, being small for gestational age (SGA), preterm birth, clinically overt cognitive, neurologic, and behavioral abnormalities, subtle neuropsychologic deficits, childhood cancer, asthma, other respiratory diseases, and acute poisoning. Some environmental toxicants, notably lead, ionizing radiation, ETS, and certain ambient air toxicants, produce adverse health effects at relatively low exposure levels during fetal or child developmental time windows. For the many associations supported by limited or inadequate epidemiologic evidence, major sources of uncertainty include the limited number of studies conducted on specific exposure-outcome relationships and methodologic limitations. The latter include (1) crude exposure indices, (2) limited range of exposure levels, (3) small sample sizes, and (4) limited knowledge and control of potential confounders. Important knowledge gaps include the role of preconceptual paternal exposures, a topic much less studied than maternal or childhood exposures. Large longitudinal studies beginning before or during early pregnancy are urgently needed to accurately measure and assess the relative importance of parental and childhood exposures and evaluate relatively subtle health outcomes such as neuropsychologic and other functional deficits. Large case-control studies are also needed to assess the role of environmental exposures and their interactions with genetic factors in relatively uncommon outcomes such as specific types of birth defects and childhood cancers. There is also an urgent need to accelerate development and use of biomarkers of exposure and genetic susceptibility in epidemiologic studies. This review supports the priority assigned by international agencies to relationships between child health and air quality (indoor and outdoor), lead, pesticides, water contaminants, and ETS. To adequately address such priorities, governments and agencies must strengthen environmental health research capacities and adopt policies to reduce parental and childhood exposures to proven and emerging environmental threats.. blood lead levels| acute lymphoblastic-leukemia| nutrition examination survey| adverse pregnancy outcomes| particulate air-pollution| disinfection by-products| waste landfill sites| basal-cell carcinoma| intrauterine growth-retardation| parental occupational exposures.	JAN-MAR-2007	blood lead levels| acute lymphoblastic-leukemia| nutrition examination survey| adverse pregnancy outcomes| particulate air-pollution| disinfection by-products| waste landfill sites| basal-cell carcinoma| intrauterine growth-retardation| parental occupational exposures	Wigle, DT; Arbuckle, TE; Walker, M; Wade, MG; Liu, SL; Krewski, D	Environmental hazards: Evidence for effects on child health		JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS		BLOOD LEAD LEVELS; ACUTE LYMPHOBLASTIC-LEUKEMIA; NUTRITION EXAMINATION SURVEY; ADVERSE PREGNANCY OUTCOMES; PARTICULATE AIR-POLLUTION; DISINFECTION BY-PRODUCTS; WASTE LANDFILL SITES; BASAL-CELL CARCINOMA; INTRAUTERINE GROWTH-RETARDATION; PARENTAL OCCUPATIONAL EXPOSURES	The human fetus, child, and adult may experience adverse health outcomes from parental or childhood exposures to environmental toxicants. The fetus and infant are especially vulnerable to toxicants that disrupt developmental processes during relatively narrow time windows. This review summarizes knowledge of associations between child health and development outcomes and environmental exposures, including lead, methylmercury, polychlorinated biphenyls (PCBs), dioxins and related polyhalogenated aromatic hydrocarbons (PHAHs), certain pesticides, environmental tobacco smoke (ETS), aeroallergens, ambient air toxicants (especially particulate matter [PM] and ozone), chlorination disinfection by-products (DBPs), sunlight, power-frequency magnetic fields, radiofrequency (RF) radiation, residential proximity to hazardous waste disposal sites, and solvents. The adverse health effects linked to such exposures include fetal death, birth defects, being small for gestational age (SGA), preterm birth, clinically overt cognitive, neurologic, and behavioral abnormalities, subtle neuropsychologic deficits, childhood cancer, asthma, other respiratory diseases, and acute poisoning. Some environmental toxicants, notably lead, ionizing radiation, ETS, and certain ambient air toxicants, produce adverse health effects at relatively low exposure levels during fetal or child developmental time windows. For the many associations supported by limited or inadequate epidemiologic evidence, major sources of uncertainty include the limited number of studies conducted on specific exposure-outcome relationships and methodologic limitations. The latter include (1) crude exposure indices, (2) limited range of exposure levels, (3) small sample sizes, and (4) limited knowledge and control of potential confounders. Important knowledge gaps include the role of preconceptual paternal exposures, a topic much less studied than maternal or childhood exposures. Large longitudinal studies beginning before or during early pregnancy are urgently needed to accurately measure and assess the relative importance of parental and childhood exposures and evaluate relatively subtle health outcomes such as neuropsychologic and other functional deficits. Large case-control studies are also needed to assess the role of environmental exposures and their interactions with genetic factors in relatively uncommon outcomes such as specific types of birth defects and childhood cancers. There is also an urgent need to accelerate development and use of biomarkers of exposure and genetic susceptibility in epidemiologic studies. This review supports the priority assigned by international agencies to relationships between child health and air quality (indoor and outdoor), lead, pesticides, water contaminants, and ETS. To adequately address such priorities, governments and agencies must strengthen environmental health research capacities and adopt policies to reduce parental and childhood exposures to proven and emerging environmental threats.	359	86	2007	37	10.1080/10937400601034563	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Effect of particulate air, pollution on lung function in adult and pediatric subjects in a Seattle panel study. Study objective: To determine whether increased exposure to particulate matter air pollution (PM), measured with personal, residential, or central site monitoring, was associated with pulmonary function decrements in either adults with COPD or children with asthma. Participants: We studied 57 adults with or without COPD and 17 children aged 6 to 13 years with physician-diagnosed asthma in Seattle during a 3-year panel study. Study design and measurements: Indoor and outdoor PM measurements were made at subjects' homes. The subjects wore personal exposure monitors for 10 consecutive 24-h periods, and PM was also measured at a central outdoor location. We assessed the within-subject effect of particulate exposure on FEV1 and peak expiratory flow (PEF) in adults, and maximal midexpiratory flow (MMEF), PEF, FEV1, and symptoms in children. Results: FEV1 decrements were associated with 1-day lagged central site PM <= 2.5 mu m in diameter (PM2.5) in adult subjects with COPD. In children not receiving antiinflammatory medication, same day indoor, outdoor, and central site exposures to PM2.5 were associated with decrements in MMEF, PEF, and FEV1. Associations with PM2.5 and lung function decrements were also observed for 1-day lagged indoor (MMEF, PEF, FEV1) and personal (PEF only) exposures. Antiinflammatory medication use in children significantly attenuated the PM effect on airflow rates and volumes. Conclusions: This study found consistent decrements in MMEF in children with asthma who were not receiving medications. It is notable that effects were observed even though PM exposures were low for an urban area. These findings suggest the need for future larger studies of PM effects in this susceptible population that repeatedly measure spirometry to include MMEF and potentially more sensitive markers of airway inflammation such as exhaled breath condensate and exhaled nitric oxide.. adults| asthma| children| copd| lung function| particulate air pollution|antiinflammatory medication use| exhaled nitric-oxide| respiratory health| asthmatic-children| symptom severity| small airways| particles| exposure| matter| association.	JUN-2006	adults| asthma| children| copd| lung function| particulate air pollution|antiinflammatory medication use| exhaled nitric-oxide| respiratory health| asthmatic-children| symptom severity| small airways| particles| exposure| matter| association	Trenga, CA; Sullivan, JH; Schildcrout, JS; Shepherd, KP; Shapiro, GG; Liu, LJS; Kaufman, JD; Koenig, JQ	Effect of particulate air, pollution on lung function in adult and pediatric subjects in a Seattle panel study		CHEST	adults; asthma; children; COPD; lung function; particulate air pollution	ANTIINFLAMMATORY MEDICATION USE; EXHALED NITRIC-OXIDE; RESPIRATORY HEALTH; ASTHMATIC-CHILDREN; SYMPTOM SEVERITY; SMALL AIRWAYS; PARTICLES; EXPOSURE; MATTER; ASSOCIATION	Study objective: To determine whether increased exposure to particulate matter air pollution (PM), measured with personal, residential, or central site monitoring, was associated with pulmonary function decrements in either adults with COPD or children with asthma. Participants: We studied 57 adults with or without COPD and 17 children aged 6 to 13 years with physician-diagnosed asthma in Seattle during a 3-year panel study. Study design and measurements: Indoor and outdoor PM measurements were made at subjects' homes. The subjects wore personal exposure monitors for 10 consecutive 24-h periods, and PM was also measured at a central outdoor location. We assessed the within-subject effect of particulate exposure on FEV1 and peak expiratory flow (PEF) in adults, and maximal midexpiratory flow (MMEF), PEF, FEV1, and symptoms in children. Results: FEV1 decrements were associated with 1-day lagged central site PM <= 2.5 mu m in diameter (PM2.5) in adult subjects with COPD. In children not receiving antiinflammatory medication, same day indoor, outdoor, and central site exposures to PM2.5 were associated with decrements in MMEF, PEF, and FEV1. Associations with PM2.5 and lung function decrements were also observed for 1-day lagged indoor (MMEF, PEF, FEV1) and personal (PEF only) exposures. Antiinflammatory medication use in children significantly attenuated the PM effect on airflow rates and volumes. Conclusions: This study found consistent decrements in MMEF in children with asthma who were not receiving medications. It is notable that effects were observed even though PM exposures were low for an urban area. These findings suggest the need for future larger studies of PM effects in this susceptible population that repeatedly measure spirometry to include MMEF and potentially more sensitive markers of airway inflammation such as exhaled breath condensate and exhaled nitric oxide.	32	86	2006	9	10.1378/chest.129.6.1614	General & Internal Medicine; Respiratory System
Epidermal growth factor receptor activation by epidermal growth factor mediates oxidant-induced goblet cell metaplasia in human airway epithelium. Mucus overproduction in inflammatory and obstructive airway diseases is associated with goblet cell (GC) metaplasia in airways. Although the mechanisms involved in GC metaplasia and mucus hypersecretion are not completely understood, association with oxidative stress and epidermal growth factor receptor (EGFIR) signaling has been reported. To explore the mechanisms involved in oxidative stress-induced GC metaplasia, cultures of differentiated normal human bronchial epithelial cells grown at the air-liquid interface were exposed to reactive oxygen species (RIDS) generated by xanthine/xanthine oxidase. EGFIR activation and signaling was assessed by measuring EGF and transforming growth factor-alpha release and EGFIR and (44/42)MAPK phosphorylation. The GC population was evaluated by confocal microscopy. ROS-induced EGFIR activation resulted in GC proliferation and increased MUC5AC gene and protein expression. Signaling was due to pro-EGF processing by tissue kallikrein (TK), which was activated by ROS-induced hyaluronan breakdown. It was inhibited by catalase, a TK inhibitor, and EGF-blocking antibodies. Exposure to recombinant TK mimicked the ROS effects, increasing the expression of MUC5AC and lactoperoxidase. In addition, ROS induced the antiapoptotic factor Bcl-2 in a TK-dependent fashion. In conclusion, ROS-induced GC metaplasia in normal human bronchial epithelial cells is associated with HA depolymerization and EGF processing by TK followed by EGFR signaling, suggesting that increases in TK activity could contribute to GC metaplasia and mucus hypersecretion in diseases such as asthma and chronic bronchitis. The data also suggest that increases in GC population could be sustained by the associated upregulation of Bcl-2 in airway epithelial cells.. egfr| goblet cells| hyaluronan| nhbe cells| tissue kallikrein|mucin gene-expression| alpha-converting-enzyme| tissue kallikrein activity| c-erbb receptors| asthmatic subjects| hyaluronic-acid| in-vitro| increases muc5ac| host-defense| mucus.	MAY-2006	egfr| goblet cells| hyaluronan| nhbe cells| tissue kallikrein|mucin gene-expression| alpha-converting-enzyme| tissue kallikrein activity| c-erbb receptors| asthmatic subjects| hyaluronic-acid| in-vitro| increases muc5ac| host-defense| mucus	Casalino-Matsuda, SM; Monzon, ME; Forteza, RM	Epidermal growth factor receptor activation by epidermal growth factor mediates oxidant-induced goblet cell metaplasia in human airway epithelium		AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY	EGFR; goblet cells; hyaluronan; NHBE cells; tissue kallikrein	MUCIN GENE-EXPRESSION; ALPHA-CONVERTING-ENZYME; TISSUE KALLIKREIN ACTIVITY; C-ERBB RECEPTORS; ASTHMATIC SUBJECTS; HYALURONIC-ACID; IN-VITRO; INCREASES MUC5AC; HOST-DEFENSE; MUCUS	Mucus overproduction in inflammatory and obstructive airway diseases is associated with goblet cell (GC) metaplasia in airways. Although the mechanisms involved in GC metaplasia and mucus hypersecretion are not completely understood, association with oxidative stress and epidermal growth factor receptor (EGFIR) signaling has been reported. To explore the mechanisms involved in oxidative stress-induced GC metaplasia, cultures of differentiated normal human bronchial epithelial cells grown at the air-liquid interface were exposed to reactive oxygen species (RIDS) generated by xanthine/xanthine oxidase. EGFIR activation and signaling was assessed by measuring EGF and transforming growth factor-alpha release and EGFIR and (44/42)MAPK phosphorylation. The GC population was evaluated by confocal microscopy. ROS-induced EGFIR activation resulted in GC proliferation and increased MUC5AC gene and protein expression. Signaling was due to pro-EGF processing by tissue kallikrein (TK), which was activated by ROS-induced hyaluronan breakdown. It was inhibited by catalase, a TK inhibitor, and EGF-blocking antibodies. Exposure to recombinant TK mimicked the ROS effects, increasing the expression of MUC5AC and lactoperoxidase. In addition, ROS induced the antiapoptotic factor Bcl-2 in a TK-dependent fashion. In conclusion, ROS-induced GC metaplasia in normal human bronchial epithelial cells is associated with HA depolymerization and EGF processing by TK followed by EGFR signaling, suggesting that increases in TK activity could contribute to GC metaplasia and mucus hypersecretion in diseases such as asthma and chronic bronchitis. The data also suggest that increases in GC population could be sustained by the associated upregulation of Bcl-2 in airway epithelial cells.	84	86	2006	11	10.1165/rcmb.2005-0386OC	Biochemistry & Molecular Biology; Cell Biology; Respiratory System
Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans. Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter - 25 nm, geometric standard deviation similar to 1.6), for 2 hr, in three separate protocols: 10 mu g/m(3) at rest, 10 and 25 mu g/m(3) with exercise, and 50 mu g/m(3) with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 mu g/m(3) UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 mu g/m(3) UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4(+) T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed.. blood leukocytes| human| monocytes| ultrafine particles|particulate air-pollution| emergency-room visits| bronchoalveolar lavage| peripheral-blood| atopic asthma| environmental aerosols| lymphocyte-activation| oxidative stress| menstrual-cycle| carbon-black.	JAN-2006	blood leukocytes| human| monocytes| ultrafine particles|particulate air-pollution| emergency-room visits| bronchoalveolar lavage| peripheral-blood| atopic asthma| environmental aerosols| lymphocyte-activation| oxidative stress| menstrual-cycle| carbon-black	Frampton, MW; Stewart, JC; Oberdorster, G; Morrow, PE; Chalupa, D; Pietropaoli, AP; Frasier, LM; Speers, DM; Cox, C; Huang, LS; Utell, MJ	Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans		ENVIRONMENTAL HEALTH PERSPECTIVES	blood leukocytes; human; monocytes; ultrafine particles	PARTICULATE AIR-POLLUTION; EMERGENCY-ROOM VISITS; BRONCHOALVEOLAR LAVAGE; PERIPHERAL-BLOOD; ATOPIC ASTHMA; ENVIRONMENTAL AEROSOLS; LYMPHOCYTE-ACTIVATION; OXIDATIVE STRESS; MENSTRUAL-CYCLE; CARBON-BLACK	Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter - 25 nm, geometric standard deviation similar to 1.6), for 2 hr, in three separate protocols: 10 mu g/m(3) at rest, 10 and 25 mu g/m(3) with exercise, and 50 mu g/m(3) with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 mu g/m(3) UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 mu g/m(3) UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4(+) T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed.	57	86	2006	8	10.1289/ehp.7962	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis. We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate-to-severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits. Peripheral blood mononuclear cells (PBMC) were isolated from children (n=53) at baseline and at the end of an 8-week supplementation period during which they received a probiotic (Lactobacillus fermentum PCC (TM)) (n=26) or a placebo (n=27). A further sample was collected at 16 weeks (8 weeks after ceasing the supplement). Cytokine (IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNF-alpha) responses to allergens (egg ovalbumin (OVA), beta lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT)), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus (HKLB)), heat-killed Staphylococcus aureus (HKSA), Staphylococcus aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared. The administration of probiotics was associated with a significant increase in T-helper type 1(Th1-type) cytokine IFN-gamma responses to PHA and SEB at the end of the supplementation period (week 8: P=0.004 and 0.046) as well as 8 weeks after ceasing supplementation (week 16: P=0.005 and 0.021) relative to baseline levels of response. No significant changes were seen in the placebo group. The increase in IFN-gamma responses to SEB was directly proportional to the decrease in the severity of AD (r=-0.445, P=0.026) over the intervention period. At the end of the supplementation period (week 8) children receiving probiotics showed significantly higher TNF-alpha responses to HKLB (P=0.018) and HKSA (P=0.011) but this was no longer evident when supplementation ceased (week 16). Although IL-13 responses to OVA were significantly reduced in children receiving probiotics after 8 weeks (P=0.008), there were no other effects on allergen-specific responses, and this effect was not sustained after ceasing supplementation (week 16). There were no effects on vaccine-specific responses, or on responses to any of the stimuli assessed. The improvement in AD severity with probiotic treatment was associated with significant increases in the capacity for Th1 IFN-gamma responses and altered responses to skin and enteric flora. This effect was still evident 2 months after the supplementation was ceased. The lack of consistent effects on allergen-specific responses suggests that the effects of probiotics may be mediated through other independent pathways, which need to be explored further.. allergy| cytokines| food allergy| infantile atopic dermatitis| probiotics|placebo-controlled trial| european task-force| intestinal microflora| consensus report| lymphoid-tissue| scorad index| infants| allergy| gut| bacteria.	DEC-2005	allergy| cytokines| food allergy| infantile atopic dermatitis| probiotics|placebo-controlled trial| european task-force| intestinal microflora| consensus report| lymphoid-tissue| scorad index| infants| allergy| gut| bacteria	Prescott, SL; Dunstan, JA; Hale, J; Breckler, L; Lehmann, H; Weston, S; Richmond, P	Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis		CLINICAL AND EXPERIMENTAL ALLERGY	allergy; cytokines; food allergy; infantile atopic dermatitis; probiotics	PLACEBO-CONTROLLED TRIAL; EUROPEAN TASK-FORCE; INTESTINAL MICROFLORA; CONSENSUS REPORT; LYMPHOID-TISSUE; SCORAD INDEX; INFANTS; ALLERGY; GUT; BACTERIA	We recently demonstrated that administration of probiotics resulted in significant clinical improvement in very young children with moderate-to-severe atopic dermatitis (AD). The purpose of this study was to determine the underlying immunological effects that are associated with these apparent clinical benefits. Peripheral blood mononuclear cells (PBMC) were isolated from children (n=53) at baseline and at the end of an 8-week supplementation period during which they received a probiotic (Lactobacillus fermentum PCC (TM)) (n=26) or a placebo (n=27). A further sample was collected at 16 weeks (8 weeks after ceasing the supplement). Cytokine (IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNF-alpha) responses to allergens (egg ovalbumin (OVA), beta lactoglobulin (BLG), house dust mite (HDM)), vaccines (tetanus toxoid (TT)), diphtheria toxoid (DT)), intestinal flora (heat-killed Lactobacillus (HKLB)), heat-killed Staphylococcus aureus (HKSA), Staphylococcus aureus enterotoxin B (SEB) and mitogen (phytohaemaglutinin (PHA)) were compared. The administration of probiotics was associated with a significant increase in T-helper type 1(Th1-type) cytokine IFN-gamma responses to PHA and SEB at the end of the supplementation period (week 8: P=0.004 and 0.046) as well as 8 weeks after ceasing supplementation (week 16: P=0.005 and 0.021) relative to baseline levels of response. No significant changes were seen in the placebo group. The increase in IFN-gamma responses to SEB was directly proportional to the decrease in the severity of AD (r=-0.445, P=0.026) over the intervention period. At the end of the supplementation period (week 8) children receiving probiotics showed significantly higher TNF-alpha responses to HKLB (P=0.018) and HKSA (P=0.011) but this was no longer evident when supplementation ceased (week 16). Although IL-13 responses to OVA were significantly reduced in children receiving probiotics after 8 weeks (P=0.008), there were no other effects on allergen-specific responses, and this effect was not sustained after ceasing supplementation (week 16). There were no effects on vaccine-specific responses, or on responses to any of the stimuli assessed. The improvement in AD severity with probiotic treatment was associated with significant increases in the capacity for Th1 IFN-gamma responses and altered responses to skin and enteric flora. This effect was still evident 2 months after the supplementation was ceased. The lack of consistent effects on allergen-specific responses suggests that the effects of probiotics may be mediated through other independent pathways, which need to be explored further.	31	86	2005	8	10.1111/j.1365-2222.2005.02376.x	Allergy; Immunology
Occupational asthma and occupational rhinitis in hairdressers. Background: Hairdressers are at risk for occupational respiratory diseases, but the risk factors, causal agents, and underlying mechanisms are not completely defined. Aim: To describe the features of a large group of hairdressers consecutively referred to our center for suspected occupational asthma (OA) over an 8-year period, the type of occupational respiratory diseases, the etiologic agents, and the diagnostic tests. Results: Forty-seven hairdressers (mean age, 25 years; range, 17 to 52 years) were studied. On the basis of the response to the specific inhalation challenge (SIC), 24 patients received a diagnosis of OA (51.1%), which was due to persulfate salts in 21 patients (87.5%), permanent hair dyes in 2 patients (8.3%), and latex in 1 patient (4.2%). Thirteen of these 24 patients (54.2%) also received a diagnosis of occupational rhinitis, which was due to persulfate salts in I I patients (84.6%) and to paraphenylenediamine in two patients (15.4%). Patients with persulfate asthma had a long period of exposure to bleaching agents, a long latent period between the start of exposure and the onset of symptoms, and a prevalent eosinophilic airway inflammation in induced sputum. The skin-prick test with ammonium persulfate performed in a subset of patients gave negative results Conclusions: In the present study, we confirmed that persulfate salts are the major agents involved in OA and occupational rhinitis in hairdressers. The positive response to the SIC in only a part of the population of symptomatic exposed workers, the period between the starting of exposure and the onset of symptoms, the type of response to the SIC, and the high frequency of association of asthma with other diseases such as dermatitis and rhinitis suggest an immunologic mechanism that remains to be elucidated.. hairdressers| occupational asthma| occupational rhinitis| persulfate|persulfate salts| airway inflammation| induced sputum| toluene diisocyanate| ammonium persulfate| inhalation| agents| prevalence| diagnosis| cell.	NOV-2005	hairdressers| occupational asthma| occupational rhinitis| persulfate|persulfate salts| airway inflammation| induced sputum| toluene diisocyanate| ammonium persulfate| inhalation| agents| prevalence| diagnosis| cell	Moscato, G; Pignatti, P; Yacoub, MR; Romano, C; Spezia, S; Perfetti, L	Occupational asthma and occupational rhinitis in hairdressers		CHEST	hairdressers; occupational asthma; occupational rhinitis; persulfate	PERSULFATE SALTS; AIRWAY INFLAMMATION; INDUCED SPUTUM; TOLUENE DIISOCYANATE; AMMONIUM PERSULFATE; INHALATION; AGENTS; PREVALENCE; DIAGNOSIS; CELL	Background: Hairdressers are at risk for occupational respiratory diseases, but the risk factors, causal agents, and underlying mechanisms are not completely defined. Aim: To describe the features of a large group of hairdressers consecutively referred to our center for suspected occupational asthma (OA) over an 8-year period, the type of occupational respiratory diseases, the etiologic agents, and the diagnostic tests. Results: Forty-seven hairdressers (mean age, 25 years; range, 17 to 52 years) were studied. On the basis of the response to the specific inhalation challenge (SIC), 24 patients received a diagnosis of OA (51.1%), which was due to persulfate salts in 21 patients (87.5%), permanent hair dyes in 2 patients (8.3%), and latex in 1 patient (4.2%). Thirteen of these 24 patients (54.2%) also received a diagnosis of occupational rhinitis, which was due to persulfate salts in I I patients (84.6%) and to paraphenylenediamine in two patients (15.4%). Patients with persulfate asthma had a long period of exposure to bleaching agents, a long latent period between the start of exposure and the onset of symptoms, and a prevalent eosinophilic airway inflammation in induced sputum. The skin-prick test with ammonium persulfate performed in a subset of patients gave negative results Conclusions: In the present study, we confirmed that persulfate salts are the major agents involved in OA and occupational rhinitis in hairdressers. The positive response to the SIC in only a part of the population of symptomatic exposed workers, the period between the starting of exposure and the onset of symptoms, the type of response to the SIC, and the high frequency of association of asthma with other diseases such as dermatitis and rhinitis suggest an immunologic mechanism that remains to be elucidated.	53	86	2005	9	10.1378/chest.128.5.3590	General & Internal Medicine; Respiratory System
The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis. Objective:The objective of this study was to evaluate montelukast 10 mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season. Methods: This was a multicenter study of 831 patients (ages 15 years-85 years) with seasonal allergen sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma. Following a single-blind, placebo run-in period of 3 days-5 days, patients were randomized to oral montelukast 10 mg (n = 415) or placebo (n = 416) daily during the 2-week, double-blind, active-treatment period. Main outcome measures: The primary endpoint was Daily Rhinitis Symptoms score, average of Daytime Nasal Symptoms and Nighttime Symptoms, as self-rated by patients on a 0-3 scale on daily diaries. Results: Montelukast reduced the Daily Rhinitis Symptoms score: difference between montelukast and placebo in mean change from baseline was -0.12 [95% CI -0.18, -0.06; p < 0.0011. Similar improvements were seen in Daytime Nasal Symptoms (-0.14 [-0.21, -0.07; p:less than or equal to 0.001]) and Nighttime Symptoms (-0.10 [-0.16,-0.04; p less than or equal to 0.001]). Improvements (p < 0.05) were seen in Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AIR by Patient and by Physician, and Rhinoconjunctivitis Quality of Life. In exploratory analyses, improvement in rhinitis symptoms was numerically (though not statistically) larger in patients with greater levels of asthma at study start. Montelukast provided benefit in the Global Evaluations of Asthma by Patient and by Physician: mean differences were -0.24 [-0.41, -0.06; p = 0.008] and -0.17 [-0.33,-0.01; p = 0.037). Similarly, as-needed P-agonist use (puffs/day) was reduced with montelukast (p less than or equal to 0.005). Conclusion: Montelukast provides significant relief from symptoms of seasonal allergic rhinitis, while also conferring a benefit for asthma, in patients with both allergic rhinitis and asthma.. allergic rhinitis| asthma| concomitant allergy and asthma| daily rhinitis symptoms| daytime nasal symptoms| montelukast| upper and lower airway disease|randomized controlled-trial| double-blind| oral montelukast| placebo| leukotrienes| inflammation| multicenter| budesonide| loratadine| airways.	OCT-2004	allergic rhinitis| asthma| concomitant allergy and asthma| daily rhinitis symptoms| daytime nasal symptoms| montelukast| upper and lower airway disease|randomized controlled-trial| double-blind| oral montelukast| placebo| leukotrienes| inflammation| multicenter| budesonide| loratadine| airways	Philip, G; Nayak, AS; Berger, WE; Leynadier, F; Vrijens, F; Dass, SB; Reiss, TF	The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis		CURRENT MEDICAL RESEARCH AND OPINION	allergic rhinitis; asthma; concomitant allergy and asthma; daily rhinitis symptoms; daytime nasal symptoms; montelukast; upper and lower airway disease	RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; ORAL MONTELUKAST; PLACEBO; LEUKOTRIENES; INFLAMMATION; MULTICENTER; BUDESONIDE; LORATADINE; AIRWAYS	Objective:The objective of this study was to evaluate montelukast 10 mg daily as treatment for allergic rhinitis in patients with symptomatic allergic rhinitis and active asthma during the allergy season. Methods: This was a multicenter study of 831 patients (ages 15 years-85 years) with seasonal allergen sensitivity, active symptoms of seasonal allergic rhinitis, and active asthma. Following a single-blind, placebo run-in period of 3 days-5 days, patients were randomized to oral montelukast 10 mg (n = 415) or placebo (n = 416) daily during the 2-week, double-blind, active-treatment period. Main outcome measures: The primary endpoint was Daily Rhinitis Symptoms score, average of Daytime Nasal Symptoms and Nighttime Symptoms, as self-rated by patients on a 0-3 scale on daily diaries. Results: Montelukast reduced the Daily Rhinitis Symptoms score: difference between montelukast and placebo in mean change from baseline was -0.12 [95% CI -0.18, -0.06; p < 0.0011. Similar improvements were seen in Daytime Nasal Symptoms (-0.14 [-0.21, -0.07; p:less than or equal to 0.001]) and Nighttime Symptoms (-0.10 [-0.16,-0.04; p less than or equal to 0.001]). Improvements (p < 0.05) were seen in Daytime Eye Symptoms and in the secondary endpoints of Global Evaluations of AIR by Patient and by Physician, and Rhinoconjunctivitis Quality of Life. In exploratory analyses, improvement in rhinitis symptoms was numerically (though not statistically) larger in patients with greater levels of asthma at study start. Montelukast provided benefit in the Global Evaluations of Asthma by Patient and by Physician: mean differences were -0.24 [-0.41, -0.06; p = 0.008] and -0.17 [-0.33,-0.01; p = 0.037). Similarly, as-needed P-agonist use (puffs/day) was reduced with montelukast (p less than or equal to 0.005). Conclusion: Montelukast provides significant relief from symptoms of seasonal allergic rhinitis, while also conferring a benefit for asthma, in patients with both allergic rhinitis and asthma.	42	86	2004	10	10.1185/030079904X3348	General & Internal Medicine; Research & Experimental Medicine
Pulmonary responses to welding fumes: Role of metal constituents. It is estimated that more than 1 million workers worldwide perform some type of welding as part of their work duties. Epidemiology studies have shown that a large number of welders experience some type of respiratory illness. Respiratory effects seen in full-time welders have included bronchitis, siderosis, asthma, and a possible increase in the incidence of lung cancer. Pulmonary infections are increased in terms of severity, duration, and frequency among welders. Inhalation exposure to welding fumes may vary due to differences in the materials used and methods employed. The chemical properties of welding fumes can be quite complex. Most welding materials are alloy mixtures of metals characterized by different steels that may contain iron, manganese, chromium, and nickel. Animal studies have indicated that the presence and combination of different metal constituents is an important determinant in the potential pneumotoxic responses associated with welding fumes. Animal models have demonstrated that stainless steel (SS) welding fumes, which contain significant levels of nickel and chromium, induce more lung injury and inflammation, and are retained in the longs longer than mild steel (MS) welding fumes, which contain mostly iron. In addition, SS fumes generated from welding processes using fluxes to protect the resulting weld contain elevated levels of soluble metals, which may affect respiratory health. Recent animal studies have indicated that the lung injury and inflammation induced by SS welding fumes that contain water-soluble metals are dependent on both the soluble and insoluble fractions of the fume. This article reviews the role that metals play in the pulmonary effects associated with welding fume exposure in workers and laboratory animals.. oil fly-ash| stainless-steel welders| mild-steel| lung-cancer| arc welders| shipyard workers| particles| health| mortality| chromium.	FEB 13-2004	oil fly-ash| stainless-steel welders| mild-steel| lung-cancer| arc welders| shipyard workers| particles| health| mortality| chromium	Antonini, JM; Taylor, MD; Zimmer, AT; Roberts, JR	Pulmonary responses to welding fumes: Role of metal constituents		JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES		OIL FLY-ASH; STAINLESS-STEEL WELDERS; MILD-STEEL; LUNG-CANCER; ARC WELDERS; SHIPYARD WORKERS; PARTICLES; HEALTH; MORTALITY; CHROMIUM	It is estimated that more than 1 million workers worldwide perform some type of welding as part of their work duties. Epidemiology studies have shown that a large number of welders experience some type of respiratory illness. Respiratory effects seen in full-time welders have included bronchitis, siderosis, asthma, and a possible increase in the incidence of lung cancer. Pulmonary infections are increased in terms of severity, duration, and frequency among welders. Inhalation exposure to welding fumes may vary due to differences in the materials used and methods employed. The chemical properties of welding fumes can be quite complex. Most welding materials are alloy mixtures of metals characterized by different steels that may contain iron, manganese, chromium, and nickel. Animal studies have indicated that the presence and combination of different metal constituents is an important determinant in the potential pneumotoxic responses associated with welding fumes. Animal models have demonstrated that stainless steel (SS) welding fumes, which contain significant levels of nickel and chromium, induce more lung injury and inflammation, and are retained in the longs longer than mild steel (MS) welding fumes, which contain mostly iron. In addition, SS fumes generated from welding processes using fluxes to protect the resulting weld contain elevated levels of soluble metals, which may affect respiratory health. Recent animal studies have indicated that the lung injury and inflammation induced by SS welding fumes that contain water-soluble metals are dependent on both the soluble and insoluble fractions of the fume. This article reviews the role that metals play in the pulmonary effects associated with welding fume exposure in workers and laboratory animals.	60	86	2004	17	10.1080/15287390490266909	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Sensitization to cross-reactive carbohydrate determinants and the ubiquitous protein profilin: mimickers of allergy. Background During the last decade, evidence has been provided for profilins and cross-reactive carbohydrate determinants (CCDs) to be capable of inducing cross-reactive IgE antibodies with little clinical relevance. Objective To investigate the prevalence of sensitization to CCD and profilin in isolated allergies (birch, timothy grass, house dust mite, pets (cat and/or dog), natural rubber latex (NRL) and hymenoptera venom). To study the contribution of anti-CCD and anti-profilin IgE antibodies as a cause of clinically irrelevant IgE for NRL and apple. Methods For the first part of the study, 100 patients with inhalant allergy, 17 patients with NRL allergy and 40 patients with venom anaphylaxis were enrolled. Diagnosis was based on a questionnaire and a positive IgE determination and skin test for relevant allergen. Patients were identified as sensitized to CCD if they had a negative prick test and positive IgE for the glycoprotein bromelain. Sensitization to profilin was assessed by IgE for rBet v 2 (recombinant birch profilin). For the second part of the study, sera containing IgE against apple (n=82) or NRL (n=38) were classified as true-negative or false-positive according to the presence or absence of an oral allergy syndrome (OAS) or NRL-induced anaphylaxis. In these patients, sensitization to CCD and profilin was evaluated as described above. Results No sensitization to bromelain-type CCD and profilin was found in isolated birch pollen or NRL allergy. In contrast, sensitization to bromelain-type CCD was found in 4/17 patients with isolated grass pollinosis, 5/24 patients with combined pollinosis (birch, timothy, mugwort) and 7/33 patients with venom anaphylaxis. Sensitization to profilin was almost restricted to patients with combined pollen allergy (5/24). In pollen-allergic individuals with a false-positive IgE against NRL the prevalence of sensitization to bromelain-type CCD and profilin IgE was higher than in NRL-allergic patients (P<0.00001 and P=0.0006, respectively). In pollen-allergic individuals with a false-positive IgE to apple, the frequency of sensitization to bromelain-type CCD was higher than in OAS patients (P=0.004). Clinically irrelevant NRL and apple were also found in four and five out of the seven patients sensitized to venom CCD, respectively. In pollinosis, clinically irrelevant NRL and apple IgE antibodies were inhibited by bromelain and recombinant birch profilin, whereas in isolated venom anaphylaxis these antibodies were inhibited by bromelain. Conclusions Patients monoallergic to NRL or birch pollen showed no sensitization to bromelain-type CCD or profilin. Sensitization to profilin and/or bromelain-type CCD, caused by pollen (timothy grass, mugwort) or hymenoptera venom allergens, can elicit false-positive IgE antibodies against NRL and apple.. carbohydrate determinants| cross-reactivity| food| hymenoptera venom| ige| latex| profilin|core alpha-1,3-linked fucose| olive tree pollen| birch pollen| ige-binding| clinical relevance| major allergen| grass-pollen| hevea-brasiliensis| food allergens| latex profilin.	JAN-2004	carbohydrate determinants| cross-reactivity| food| hymenoptera venom| ige| latex| profilin|core alpha-1,3-linked fucose| olive tree pollen| birch pollen| ige-binding| clinical relevance| major allergen| grass-pollen| hevea-brasiliensis| food allergens| latex profilin	Ebo, DG; Hagendorens, MM; Bridts, CH; De Clerck, LS; Stevens, WJ	Sensitization to cross-reactive carbohydrate determinants and the ubiquitous protein profilin: mimickers of allergy		CLINICAL AND EXPERIMENTAL ALLERGY	carbohydrate determinants; cross-reactivity; food; hymenoptera venom; IgE; latex; profilin	CORE ALPHA-1,3-LINKED FUCOSE; OLIVE TREE POLLEN; BIRCH POLLEN; IGE-BINDING; CLINICAL RELEVANCE; MAJOR ALLERGEN; GRASS-POLLEN; HEVEA-BRASILIENSIS; FOOD ALLERGENS; LATEX PROFILIN	Background During the last decade, evidence has been provided for profilins and cross-reactive carbohydrate determinants (CCDs) to be capable of inducing cross-reactive IgE antibodies with little clinical relevance. Objective To investigate the prevalence of sensitization to CCD and profilin in isolated allergies (birch, timothy grass, house dust mite, pets (cat and/or dog), natural rubber latex (NRL) and hymenoptera venom). To study the contribution of anti-CCD and anti-profilin IgE antibodies as a cause of clinically irrelevant IgE for NRL and apple. Methods For the first part of the study, 100 patients with inhalant allergy, 17 patients with NRL allergy and 40 patients with venom anaphylaxis were enrolled. Diagnosis was based on a questionnaire and a positive IgE determination and skin test for relevant allergen. Patients were identified as sensitized to CCD if they had a negative prick test and positive IgE for the glycoprotein bromelain. Sensitization to profilin was assessed by IgE for rBet v 2 (recombinant birch profilin). For the second part of the study, sera containing IgE against apple (n=82) or NRL (n=38) were classified as true-negative or false-positive according to the presence or absence of an oral allergy syndrome (OAS) or NRL-induced anaphylaxis. In these patients, sensitization to CCD and profilin was evaluated as described above. Results No sensitization to bromelain-type CCD and profilin was found in isolated birch pollen or NRL allergy. In contrast, sensitization to bromelain-type CCD was found in 4/17 patients with isolated grass pollinosis, 5/24 patients with combined pollinosis (birch, timothy, mugwort) and 7/33 patients with venom anaphylaxis. Sensitization to profilin was almost restricted to patients with combined pollen allergy (5/24). In pollen-allergic individuals with a false-positive IgE against NRL the prevalence of sensitization to bromelain-type CCD and profilin IgE was higher than in NRL-allergic patients (P<0.00001 and P=0.0006, respectively). In pollen-allergic individuals with a false-positive IgE to apple, the frequency of sensitization to bromelain-type CCD was higher than in OAS patients (P=0.004). Clinically irrelevant NRL and apple were also found in four and five out of the seven patients sensitized to venom CCD, respectively. In pollinosis, clinically irrelevant NRL and apple IgE antibodies were inhibited by bromelain and recombinant birch profilin, whereas in isolated venom anaphylaxis these antibodies were inhibited by bromelain. Conclusions Patients monoallergic to NRL or birch pollen showed no sensitization to bromelain-type CCD or profilin. Sensitization to profilin and/or bromelain-type CCD, caused by pollen (timothy grass, mugwort) or hymenoptera venom allergens, can elicit false-positive IgE antibodies against NRL and apple.	50	86	2004	8	10.1111/j.1365-2222.2004.01837.x	Allergy; Immunology
"Hypersensitivity reactions to chemotherapeutic drugs. There is an ever-increasing number of therapeutics used to treat cancer. A recent publication listed 86 currently available antineoplastic medications. Despite this large number, hypersensitivity reactions are not common except with platinum compounds (cisplatin, carboplatin), epipodophyllotoxins (teniposide, etoposide), asparaginase, taxanes (paclitaxel), and procarbazine. Doxorubicin and 6-mercaptopurine are occasionally associated with hypersensitivity reaction. Comparable reactions with other chemotherapeutic agents are. uncommon; many are only anecdotal reports. Reactions associated with individual drugs are discussed in detail. The mechanisms responsible for most of these reactions are not known, as they have generally not been evaluated. The term ""hypersensitivity"" is widely used in the chemotherapy literature without a common definition. Hypersensitivity is defined here as an unexpected reaction with signs and symptoms not consistent with known toxicity of the drug. Most reactions are coincident with or within hours of drug administration. Almost all are associated with parenteral administration. Symptoms include flushing, alterations in heart rate and blood pressure, dyspnea and bronchospasm, back pain, fever, pruritus, nausea and all types of rashes. Some cases may be due to non-immune mediated release of histamine or cytokines, as many patients can subsequently tolerate re-exposure after pretreatment with steroids and antihistamine, and slow readministration of the drug. This is more compatible with a graded challenge, than desensitization and is generally successful for taxanes, less so for platinum compounds. In most cases hypersensitivity reactions are associated with the specific chemotherapeutic drug. Reaction rates may vary with different forms of the drugs, e.g. pegylated. Occasionally excipients such as Cremaphor EL may induce hypersensitivity reactions.. hypersensitivity| allergy| chemotherapy| desensitization| drug asparaginase| platinum compounds| epipodophyllotoxins| taxanes|acute lymphoblastic-leukemia| pegylated liposomal doxorubicin| desensitization protocol| allergic reactions| carboplatin| paclitaxel| asparaginase| cancer| cyclophosphamide| docetaxel."	JUN-2003	hypersensitivity| allergy| chemotherapy| desensitization| drug asparaginase| platinum compounds| epipodophyllotoxins| taxanes|acute lymphoblastic-leukemia| pegylated liposomal doxorubicin| desensitization protocol| allergic reactions| carboplatin| paclitaxel| asparaginase| cancer| cyclophosphamide| docetaxel	Shepherd, GM	Hypersensitivity reactions to chemotherapeutic drugs		CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY	hypersensitivity; allergy; chemotherapy; desensitization; drug asparaginase; platinum compounds; epipodophyllotoxins; taxanes	ACUTE LYMPHOBLASTIC-LEUKEMIA; PEGYLATED LIPOSOMAL DOXORUBICIN; DESENSITIZATION PROTOCOL; ALLERGIC REACTIONS; CARBOPLATIN; PACLITAXEL; ASPARAGINASE; CANCER; CYCLOPHOSPHAMIDE; DOCETAXEL	"There is an ever-increasing number of therapeutics used to treat cancer. A recent publication listed 86 currently available antineoplastic medications. Despite this large number, hypersensitivity reactions are not common except with platinum compounds (cisplatin, carboplatin), epipodophyllotoxins (teniposide, etoposide), asparaginase, taxanes (paclitaxel), and procarbazine. Doxorubicin and 6-mercaptopurine are occasionally associated with hypersensitivity reaction. Comparable reactions with other chemotherapeutic agents are. uncommon; many are only anecdotal reports. Reactions associated with individual drugs are discussed in detail. The mechanisms responsible for most of these reactions are not known, as they have generally not been evaluated. The term ""hypersensitivity"" is widely used in the chemotherapy literature without a common definition. Hypersensitivity is defined here as an unexpected reaction with signs and symptoms not consistent with known toxicity of the drug. Most reactions are coincident with or within hours of drug administration. Almost all are associated with parenteral administration. Symptoms include flushing, alterations in heart rate and blood pressure, dyspnea and bronchospasm, back pain, fever, pruritus, nausea and all types of rashes. Some cases may be due to non-immune mediated release of histamine or cytokines, as many patients can subsequently tolerate re-exposure after pretreatment with steroids and antihistamine, and slow readministration of the drug. This is more compatible with a graded challenge, than desensitization and is generally successful for taxanes, less so for platinum compounds. In most cases hypersensitivity reactions are associated with the specific chemotherapeutic drug. Reaction rates may vary with different forms of the drugs, e.g. pegylated. Occasionally excipients such as Cremaphor EL may induce hypersensitivity reactions."	46	86	2003	10	10.1385/CRIAI:24:3:253	Allergy; Immunology
Performance and costs of particle air filtration technologies. This paper predicts the reductions in the indoor mass concentrations of particles attainable from use of filters in building supply airstreams and also from use of stand-alone fan-filter units. Filters with a wide efficiency range are considered. Predicted concentration reductions are provided for indoor-generated particles containing dust-mite and cat allergen, for environmental tobacco smoke (ETS) particles, and for outdoor air fine-mode particles. Additionally, this paper uses a simple model and available data to estimate the energy and total costs of the filtration options. Predicted reductions in cat and dust-mite allergen concentrations range from 20 to 80%. To obtain substantial, e.g. 50%, reductions in indoor concentrations of these allergens, the rate of airflow through the filter must be at least a few indoor volumes per hour. Increasing filter efficiencies above approximately ASHRAE Dust Spot 65% does not significantly reduce predicted indoor concentrations of these allergens. For ETS particles and outdoor fine-mode particles, calculations indicate that relatively large, e.g. 80%, decreases in indoor concentrations are attainable with practical filter efficiencies and flow rates. Increasing the filter efficiency above ASHRAE 85% results in only modest predicted incremental decreases in indoor concentration. Energy costs and total costs can be similar for filtration using filters with a wide range of efficiency ratings. Total estimated filtration costs of approximately $0.70 to $1.80 per person per month are insignificant relative to salaries, rent, or health insurance costs.. allergen| building| concentration| filtration| particle| reduction|tobacco-smoke particles| aerosol fraction| mite allergen| deposition| pollen| penetration| exposure| outdoor.	DEC-2002	allergen| building| concentration| filtration| particle| reduction|tobacco-smoke particles| aerosol fraction| mite allergen| deposition| pollen| penetration| exposure| outdoor	Fisk, WJ; Faulkner, D; Palonen, J; Seppanen, O	Performance and costs of particle air filtration technologies		INDOOR AIR	allergen; building; concentration; filtration; particle; reduction	TOBACCO-SMOKE PARTICLES; AEROSOL FRACTION; MITE ALLERGEN; DEPOSITION; POLLEN; PENETRATION; EXPOSURE; OUTDOOR	This paper predicts the reductions in the indoor mass concentrations of particles attainable from use of filters in building supply airstreams and also from use of stand-alone fan-filter units. Filters with a wide efficiency range are considered. Predicted concentration reductions are provided for indoor-generated particles containing dust-mite and cat allergen, for environmental tobacco smoke (ETS) particles, and for outdoor air fine-mode particles. Additionally, this paper uses a simple model and available data to estimate the energy and total costs of the filtration options. Predicted reductions in cat and dust-mite allergen concentrations range from 20 to 80%. To obtain substantial, e.g. 50%, reductions in indoor concentrations of these allergens, the rate of airflow through the filter must be at least a few indoor volumes per hour. Increasing filter efficiencies above approximately ASHRAE Dust Spot 65% does not significantly reduce predicted indoor concentrations of these allergens. For ETS particles and outdoor fine-mode particles, calculations indicate that relatively large, e.g. 80%, decreases in indoor concentrations are attainable with practical filter efficiencies and flow rates. Increasing the filter efficiency above ASHRAE 85% results in only modest predicted incremental decreases in indoor concentration. Energy costs and total costs can be similar for filtration using filters with a wide range of efficiency ratings. Total estimated filtration costs of approximately $0.70 to $1.80 per person per month are insignificant relative to salaries, rent, or health insurance costs.	37	86	2002	12	10.1034/j.1600-0668.2002.01136.x	Construction & Building Technology; Engineering; Public, Environmental & Occupational Health
An update on pollen and fungal spore aerobiology. Changes in climate are altering pollen distribution. Predictive modeling can be used to forecast long- and short-term changes in pollen concentrations. Increasing evidence confirms the presence of pollen allergens on small, respirable particles in the air, explaining the occurrence of pollen-season increases in asthma. Like pollens, above ground indoor fungal aerosols primarily reflect outdoor concentrations. Basement spore concentrations might be higher and reflective of local sources. Fungal presence in the indoor or outdoor air can be monitored on an area basis or with personal monitors. The samples can be analyzed by means of microscopy, culture, DNA probes, HPLC, or immunodetection. Total fungal biomass can be estimated on the basis of measurements of ergosterol or glucan in environmental samples. Unfortunately, there are no generally accepted standards for interpretation of fungal levels in indoor or outdoor air. At present, the best approach to indoor fungal control is moisture control in the indoor environment. This will essentially prevent fungal growth, except from extraordinary events.. pollen| fungi| aerobiology| spores| allergen| immunodetection|in-house dust| thunderstorm-associated asthma| volatile organic-compounds| water-damaged buildings| reported home dampness| grass-pollen| stachybotrys-chartarum| residential characteristics| respiratory symptoms| indoor air.	OCT-2002	pollen| fungi| aerobiology| spores| allergen| immunodetection|in-house dust| thunderstorm-associated asthma| volatile organic-compounds| water-damaged buildings| reported home dampness| grass-pollen| stachybotrys-chartarum| residential characteristics| respiratory symptoms| indoor air	Burge, HA	An update on pollen and fungal spore aerobiology		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	pollen; fungi; aerobiology; spores; allergen; immunodetection	IN-HOUSE DUST; THUNDERSTORM-ASSOCIATED ASTHMA; VOLATILE ORGANIC-COMPOUNDS; WATER-DAMAGED BUILDINGS; REPORTED HOME DAMPNESS; GRASS-POLLEN; STACHYBOTRYS-CHARTARUM; RESIDENTIAL CHARACTERISTICS; RESPIRATORY SYMPTOMS; INDOOR AIR	Changes in climate are altering pollen distribution. Predictive modeling can be used to forecast long- and short-term changes in pollen concentrations. Increasing evidence confirms the presence of pollen allergens on small, respirable particles in the air, explaining the occurrence of pollen-season increases in asthma. Like pollens, above ground indoor fungal aerosols primarily reflect outdoor concentrations. Basement spore concentrations might be higher and reflective of local sources. Fungal presence in the indoor or outdoor air can be monitored on an area basis or with personal monitors. The samples can be analyzed by means of microscopy, culture, DNA probes, HPLC, or immunodetection. Total fungal biomass can be estimated on the basis of measurements of ergosterol or glucan in environmental samples. Unfortunately, there are no generally accepted standards for interpretation of fungal levels in indoor or outdoor air. At present, the best approach to indoor fungal control is moisture control in the indoor environment. This will essentially prevent fungal growth, except from extraordinary events.	110	86	2002	9	10.1067/mai.2002.128674	Allergy; Immunology
New insights into the relationship between airway inflammation and asthma. Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -for reasons that remain to be established -that asthma occurs.. airway hyper-responsiveness| airway smooth muscle| asthma| eosinophils| inflammation|smooth-muscle cells| obstructive pulmonary-disease| expiratory flow variability| mast-cells| bronchial hyperreactivity| eosinophilic bronchitis| population-sample| nedocromil sodium| deep inspiration| induced sputum.	AUG-2002	airway hyper-responsiveness| airway smooth muscle| asthma| eosinophils| inflammation|smooth-muscle cells| obstructive pulmonary-disease| expiratory flow variability| mast-cells| bronchial hyperreactivity| eosinophilic bronchitis| population-sample| nedocromil sodium| deep inspiration| induced sputum	Wardlaw, AJ; Brightling, CE; Green, R; Woltmann, G; Bradding, P; Pavord, ID	New insights into the relationship between airway inflammation and asthma		CLINICAL SCIENCE	airway hyper-responsiveness; airway smooth muscle; asthma; eosinophils; inflammation	SMOOTH-MUSCLE CELLS; OBSTRUCTIVE PULMONARY-DISEASE; EXPIRATORY FLOW VARIABILITY; MAST-CELLS; BRONCHIAL HYPERREACTIVITY; EOSINOPHILIC BRONCHITIS; POPULATION-SAMPLE; NEDOCROMIL SODIUM; DEEP INSPIRATION; INDUCED SPUTUM	Asthma is a condition characterized by variable airflow obstruction, airway hyper-responsiveness (AHR) and airway inflammation which is usually, but not invariably, eosinophilic. Current thoughts on the pathogenesis of asthma are focused on the idea that it is caused by an inappropriate response of the specific immune system to harmless antigens, particularly allergens such as cat dander and house dust mite, that result in Th2-mediated chronic inflammation. However, the relationship between inflammation and asthma is complex, with no good correlation between the severity of inflammation, at least as measured by the number of eosinophils, and the severity of asthma. In addition, there are a number of conditions, such as eosinophilic bronchitis and allergic rhinitis, in which there is a Th2-mediated inflammatory response, but no asthma, as measured by variable airflow obstruction or AHR. Bronchoconstriction can also occur without obvious airway inflammation, and neutrophilic inflammation can in some cases be associated with asthma. When we compared the immunopathology of eosinophilic bronchitis and asthma, the only difference we observed was that, in asthma, the airway smooth muscle (ASM) was infiltrated by mast cells, suggesting that airway obstruction and AHR are due to an ASM mast cell myositis. This observation emphasizes that the features that characterize asthma, as opposed to bronchitis, are due to abnormalities in smooth muscle responsiveness, which could be intrinsic or acquired, and that inflammation is only relevant in that it leads to these abnormalities. It also emphasizes the importance of micro-localization as an organizing principle in physiological responses to airway inflammation. Thus, if inflammation is localized to the epithelium and lamina propria, then the symptoms of bronchitis (cough and mucus hypersecretion) result, and it is only if the ASM is involved -for reasons that remain to be established -that asthma occurs.	68	86	2002	11		Research & Experimental Medicine
Photoallergic contact dermatitis is uncommon. Background Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare. Objectives To analyse the data from 2715 patients who underwent photopatch testing at St John's Institute of Dermatology during the period 1983-98. Methods A retrospective analysis of all positive photopatch test episodes was undertaken with the results retrieved from the environmental dermatology database and further verified with the original archived patch test documentation for each individual patient. Results In 111 patients with positive reactions (4.1%), there were 155 AC or PA reactions to allergens in the photopatch test series. Eighty PA reactions were observed in 62 (2.3%) patients (32 men and 30 women, age range 28-75 years), with UV filters accounting for 52 positive reactions (65%). drugs 16 (20%), musk ambrette 11 (14%) and the antiseptic trichlorocarbanilide one (1%). The most common UV filter photoallergen was benzophenone-3 with 14 positive results, followed by benzophenone-10 (n = 9), isopropyl dibenzoylmethane (n = 6), p-aminobenzoic acid (PABA) (n = 5), octyl dimethyl PABA (n = 5), butyl methoxydibenzoylmethane (n = 4), isoamyl methoxycinnamate (n = 2), ethyl methoxycinnamate (n = 2), octyl methoxycinnamate (n = 2). amyl dimethyl PABA (n = 2) and phenylbenzimidazole sulphonic acid (n = 1). A similar number of AC reactions to UV filters was detected in this study. Thus 49 patients (1.8%) had a total of 75 reactions: 51 due to UV filters and 24 as a result of exposure to fragrances and therapeutic agents. Benzophenone-10 accounted for 13 AC reactions and benzophenone-3 for eight reactions. Twenty-two patients had a PA reaction alone, whereas 19 patients had chronic actinic dermatitis and 15 patients polymorphic light eruption (PLE) in addition. Thus, 34 of the 62 patients (55%) had a preceding underlying photodermatosis. Conclusions These results show a low yield of positive photopatch tests. Thus, despite the large increase in the use of UV filters over the last decade, the development of PA reactions remains rare. Furthermore, most of the common UV filter photoallergens identified in this study, including PABA, amyl dimethyl PABA and benzophenone-10. are now rarely used in sunscreen manufacture, while isopropyl dibenzoylmethane was voluntarily removed from the market in 1993. Currently, benzophenone-3 is the commonest contact photoallergen still in widespread use. In contrast, the UVB filter octyl methoxycinnamate, used in a number of sunscreens, produced only two positive PA reactions in 12 years of testing. Nevertheless, although these reactions are extremely rare, patients with photodermatoses such as PIE and chronic actinic dermatitis do represent a group of patients at increased risk of developing photoallergy. Further photopatch test series should be regularly reviewed and updated, as the relevance of individual photoallergens changes over time. Currently, there is no evidence that PA reactions represent a common clinical problem.. benzophenone-3| photoallergy| photodermatosis| photopatch test| sunscreens| ultraviolet filters|scandinavian multicenter photopatch| photocontact sensitization| photosensitivity| sensitivity| experience| sunscreens| 5-year.	OCT-2001	benzophenone-3| photoallergy| photodermatosis| photopatch test| sunscreens| ultraviolet filters|scandinavian multicenter photopatch| photocontact sensitization| photosensitivity| sensitivity| experience| sunscreens| 5-year	Darvay, A; White, IR; Rycroft, RJG; Jones, AB; Hawk, JL; McFadden, JP	Photoallergic contact dermatitis is uncommon		BRITISH JOURNAL OF DERMATOLOGY	benzophenone-3; photoallergy; photodermatosis; photopatch test; sunscreens; ultraviolet filters	SCANDINAVIAN MULTICENTER PHOTOPATCH; PHOTOCONTACT SENSITIZATION; PHOTOSENSITIVITY; SENSITIVITY; EXPERIENCE; SUNSCREENS; 5-YEAR	Background Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare. Objectives To analyse the data from 2715 patients who underwent photopatch testing at St John's Institute of Dermatology during the period 1983-98. Methods A retrospective analysis of all positive photopatch test episodes was undertaken with the results retrieved from the environmental dermatology database and further verified with the original archived patch test documentation for each individual patient. Results In 111 patients with positive reactions (4.1%), there were 155 AC or PA reactions to allergens in the photopatch test series. Eighty PA reactions were observed in 62 (2.3%) patients (32 men and 30 women, age range 28-75 years), with UV filters accounting for 52 positive reactions (65%). drugs 16 (20%), musk ambrette 11 (14%) and the antiseptic trichlorocarbanilide one (1%). The most common UV filter photoallergen was benzophenone-3 with 14 positive results, followed by benzophenone-10 (n = 9), isopropyl dibenzoylmethane (n = 6), p-aminobenzoic acid (PABA) (n = 5), octyl dimethyl PABA (n = 5), butyl methoxydibenzoylmethane (n = 4), isoamyl methoxycinnamate (n = 2), ethyl methoxycinnamate (n = 2), octyl methoxycinnamate (n = 2). amyl dimethyl PABA (n = 2) and phenylbenzimidazole sulphonic acid (n = 1). A similar number of AC reactions to UV filters was detected in this study. Thus 49 patients (1.8%) had a total of 75 reactions: 51 due to UV filters and 24 as a result of exposure to fragrances and therapeutic agents. Benzophenone-10 accounted for 13 AC reactions and benzophenone-3 for eight reactions. Twenty-two patients had a PA reaction alone, whereas 19 patients had chronic actinic dermatitis and 15 patients polymorphic light eruption (PLE) in addition. Thus, 34 of the 62 patients (55%) had a preceding underlying photodermatosis. Conclusions These results show a low yield of positive photopatch tests. Thus, despite the large increase in the use of UV filters over the last decade, the development of PA reactions remains rare. Furthermore, most of the common UV filter photoallergens identified in this study, including PABA, amyl dimethyl PABA and benzophenone-10. are now rarely used in sunscreen manufacture, while isopropyl dibenzoylmethane was voluntarily removed from the market in 1993. Currently, benzophenone-3 is the commonest contact photoallergen still in widespread use. In contrast, the UVB filter octyl methoxycinnamate, used in a number of sunscreens, produced only two positive PA reactions in 12 years of testing. Nevertheless, although these reactions are extremely rare, patients with photodermatoses such as PIE and chronic actinic dermatitis do represent a group of patients at increased risk of developing photoallergy. Further photopatch test series should be regularly reviewed and updated, as the relevance of individual photoallergens changes over time. Currently, there is no evidence that PA reactions represent a common clinical problem.	25	86	2001	5	10.1046/j.1365-2133.2001.04458.x	Dermatology
Do pregnant women report use of dispensed medications?. Surveillance of drug safety in pregnancy often draws on administrative prescription registries. Noncompliance in the use of prescribed medication may be frequent among pregnant women owing to their fear of fetotoxic side effects. To estimate compliance in the use of prescription drugs dispensed during pregnancy, we compared prescription data from the North Jutland Prescription Database with information on drug use provided by pregnant women to the Danish National Birth Cohort (DNBC), which is a health inter-view survey. We used the North Jutland Prescription Database to identify all prescription drugs dispensed during pregnancy for the 2,041 women who were enrolled in the DNBC in the County of North Jutland, Denmark. Compliance was defined as the probability of reporting drug use in DNBC after purchasing a dispensed prescription drug. The overall compliance to drugs purchased within 120 days before the interview was 43% (95% confidence interval = 40-46). Drugs used for treating chronic diseases, for example, beta-blockers, insulin, thyroid hormones, and diuretic and antiepileptic drugs, were always reported to be used, but compliance was low for drugs used for local or short-term treatment such as antihistamines, antibiotics, antacids, nonsteroid anti-inflammatory drugs, and gynecologic drugs. Thus, for the latter drug groups the prescription database may provide an incomplete identification of exposure, Neither data source is unbiased regarding actual drug intake. Nevertheless, our results indicate that for some drug groups risk assessment studies based on prescription data may produce false negative results as a result of noncompliance.. compliance| exposure misclassification| pregnancy| prescription database| risk assessment| validation study|drug-use| congenital-malformations| patient compliance| questionnaire data| recall bias| exposure| outcomes| records| asthma| population.	SEP-2001	compliance| exposure misclassification| pregnancy| prescription database| risk assessment| validation study|drug-use| congenital-malformations| patient compliance| questionnaire data| recall bias| exposure| outcomes| records| asthma| population	Olesen, C; Sondergaard, C; Thrane, N; Nielsen, GL; de Jong-van den Berg, L; Olsen, J	Do pregnant women report use of dispensed medications?		EPIDEMIOLOGY	compliance; exposure misclassification; pregnancy; prescription database; risk assessment; validation study	DRUG-USE; CONGENITAL-MALFORMATIONS; PATIENT COMPLIANCE; QUESTIONNAIRE DATA; RECALL BIAS; EXPOSURE; OUTCOMES; RECORDS; ASTHMA; POPULATION	Surveillance of drug safety in pregnancy often draws on administrative prescription registries. Noncompliance in the use of prescribed medication may be frequent among pregnant women owing to their fear of fetotoxic side effects. To estimate compliance in the use of prescription drugs dispensed during pregnancy, we compared prescription data from the North Jutland Prescription Database with information on drug use provided by pregnant women to the Danish National Birth Cohort (DNBC), which is a health inter-view survey. We used the North Jutland Prescription Database to identify all prescription drugs dispensed during pregnancy for the 2,041 women who were enrolled in the DNBC in the County of North Jutland, Denmark. Compliance was defined as the probability of reporting drug use in DNBC after purchasing a dispensed prescription drug. The overall compliance to drugs purchased within 120 days before the interview was 43% (95% confidence interval = 40-46). Drugs used for treating chronic diseases, for example, beta-blockers, insulin, thyroid hormones, and diuretic and antiepileptic drugs, were always reported to be used, but compliance was low for drugs used for local or short-term treatment such as antihistamines, antibiotics, antacids, nonsteroid anti-inflammatory drugs, and gynecologic drugs. Thus, for the latter drug groups the prescription database may provide an incomplete identification of exposure, Neither data source is unbiased regarding actual drug intake. Nevertheless, our results indicate that for some drug groups risk assessment studies based on prescription data may produce false negative results as a result of noncompliance.	34	86	2001	5	10.1097/00001648-200109000-00006	Public, Environmental & Occupational Health
Model for forecasting Olea europaea L. airborne pollen in South-West Andalusia, Spain. Data on predicted average and maximum air-borne pollen concentrations and the dates on which these maximum values are expected are of undoubted value to allergists and allergy sufferers, as well as to agronomists. This paper reports on the development of predictive models for calculating total annual pollen output, on the basis of pollen and weather data compiled over the last 19 years (1982-2000) for Cordoba (Spain). Models were tested in order to predict the 2000 pollen season; in addition, and in view of the heavy rainfall recorded in spring 2000, the 1982-1998 data set was used to test the model for 1999. The results of the multiple regression analysis show that the variables exerting the greatest influence on the pollen index were rainfall in March and temperatures over the months prior to the flowering period. For prediction of maximum values and dates on which these values might be expected, the start of the pollen season was used as an additional independent variable. Temperature proved the best variable for this prediction. Results improved when the 5-day moving average was taken into account. Testing of the predictive model for 1999 and 2000 yielded fairly similar results. In both cases, the difference between expected and observed pollen data was no greater than 10%. However, significant differences were recorded between forecast and expected maximum and minimum values, owing to the influence of rainfall during the flowering period.. aerobiology| forecasting| olea europaea| pollen index| pollen production|atmosphere.	JUL-2001	aerobiology| forecasting| olea europaea| pollen index| pollen production|atmosphere	Galan, C; Carinanos, P; Garcia-Mozo, H; Alcazar, P; Dominguez-Vilches, E	Model for forecasting Olea europaea L. airborne pollen in South-West Andalusia, Spain		INTERNATIONAL JOURNAL OF BIOMETEOROLOGY	aerobiology; forecasting; Olea europaea; pollen index; pollen production	ATMOSPHERE	Data on predicted average and maximum air-borne pollen concentrations and the dates on which these maximum values are expected are of undoubted value to allergists and allergy sufferers, as well as to agronomists. This paper reports on the development of predictive models for calculating total annual pollen output, on the basis of pollen and weather data compiled over the last 19 years (1982-2000) for Cordoba (Spain). Models were tested in order to predict the 2000 pollen season; in addition, and in view of the heavy rainfall recorded in spring 2000, the 1982-1998 data set was used to test the model for 1999. The results of the multiple regression analysis show that the variables exerting the greatest influence on the pollen index were rainfall in March and temperatures over the months prior to the flowering period. For prediction of maximum values and dates on which these values might be expected, the start of the pollen season was used as an additional independent variable. Temperature proved the best variable for this prediction. Results improved when the 5-day moving average was taken into account. Testing of the predictive model for 1999 and 2000 yielded fairly similar results. In both cases, the difference between expected and observed pollen data was no greater than 10%. However, significant differences were recorded between forecast and expected maximum and minimum values, owing to the influence of rainfall during the flowering period.	28	86	2001	5	10.1007/s004840100089	Biophysics; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences; Physiology
Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. Background: Wheezing illnesses cause major morbidity in infants and are frequent precursors to asthma. Objective: We sought to examine environmental factors associated with recurrent wheezing in inner-city environments. Methods: The Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n = 560) in Baltimore, Boston, New York, and St Louis. Environmental assessments included allergen exposure and, in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age 3 years. Results: Cumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively; P <= .01). Differences in house dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze. Conclusions: In inner-city environments children with the highest exposure to specific allergens and bacteria during their first year were least likely to have recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial and suggest new preventive strategies for wheezing and allergic diseases.. asthma| atopy| allergen exposure| microbial exposure| inner city|house-dust mite| childhood asthma| inner-city| immune development| virus-infection| dog ownership| united-states| lung-function| birth-cohort| cat allergen.	SEP-2014	asthma| atopy| allergen exposure| microbial exposure| inner city|house-dust mite| childhood asthma| inner-city| immune development| virus-infection| dog ownership| united-states| lung-function| birth-cohort| cat allergen	Lynch, SV; Wood, RA; Boushey, H; Bacharier, LB; Bloomberg, GR; Kattan, M; O'Connor, GT; Sandel, MT; Calatroni, A; Matsui, E; Johnson, CC; Lynn, H; Visness, CM; Jaffee, KF; Gergen, PJ; Gold, DR; Wright, RJ; Fujimura, K; Rauch, M; Busse, WW; Gern, JE	Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Asthma; atopy; allergen exposure; microbial exposure; inner city	HOUSE-DUST MITE; CHILDHOOD ASTHMA; INNER-CITY; IMMUNE DEVELOPMENT; VIRUS-INFECTION; DOG OWNERSHIP; UNITED-STATES; LUNG-FUNCTION; BIRTH-COHORT; CAT ALLERGEN	Background: Wheezing illnesses cause major morbidity in infants and are frequent precursors to asthma. Objective: We sought to examine environmental factors associated with recurrent wheezing in inner-city environments. Methods: The Urban Environment and Childhood Asthma study examined a birth cohort at high risk for asthma (n = 560) in Baltimore, Boston, New York, and St Louis. Environmental assessments included allergen exposure and, in a nested case-control study of 104 children, the bacterial content of house dust collected in the first year of life. Associations were determined among environmental factors, aeroallergen sensitization, and recurrent wheezing at age 3 years. Results: Cumulative allergen exposure over the first 3 years was associated with allergic sensitization, and sensitization at age 3 years was related to recurrent wheeze. In contrast, first-year exposure to cockroach, mouse, and cat allergens was negatively associated with recurrent wheeze (odds ratio, 0.60, 0.65, and 0.75, respectively; P <= .01). Differences in house dust bacterial content in the first year, especially reduced exposure to specific Firmicutes and Bacteriodetes, was associated with atopy and atopic wheeze. Exposure to high levels of both allergens and this subset of bacteria in the first year of life was most common among children without atopy or wheeze. Conclusions: In inner-city environments children with the highest exposure to specific allergens and bacteria during their first year were least likely to have recurrent wheeze and allergic sensitization. These findings suggest that concomitant exposure to high levels of certain allergens and bacteria in early life might be beneficial and suggest new preventive strategies for wheezing and allergic diseases.	60	85	2014	21	10.1016/j.jaci.2014.04.018	Allergy; Immunology
CD301b(+) Dermal Dendritic Cells Drive T Helper 2 Cell-Mediated Immunity. Unlike other types of T helper (Th) responses, whether the development of Th2 cells requires instruction from particular subset of dendritic cells (DCs) remains unclear. By using an in vivo depletion approach, we have shown that DCs expressing CD301b were required for the generation of Th2 cells after subcutaneous immunization with ovalbumin (OVA) along with papain or alum. CD301b(+) DCs are distinct from epidermal or CD207(+) dermal DCs (DDCs) and were responsible for transporting antigen injected subcutaneously with Th2-type adjuvants. Transient depletion of CD301b(+) DCs resulted in less effective accumulation and decreased expression of CD69 by polyclonal CD4(+) T cells in the lymph node. Moreover, despite intact cell division and interferon-gamma production, CD301b(+) DC depletion led to blunted interleukin-4 production by OVA-specific OT-II transgenic CD4(+) T cells and significantly impaired Th2 cell development upon infection with Nippostrongylus brasiliensis. These results reveal CD301b(+) DDCs as the key mediators of Th2 immunity.. cd4(+) t-cells| transcription factor gata-3| helper type-2 response| dust mite allergen| in-vivo| langerhans cells| mucosal immunization| airway inflammation| helminth infection| th2 cells.	OCT 17-2013	cd4(+) t-cells| transcription factor gata-3| helper type-2 response| dust mite allergen| in-vivo| langerhans cells| mucosal immunization| airway inflammation| helminth infection| th2 cells	Kumamoto, Y; Linehan, M; Weinstein, JS; Laidlaw, BJ; Craft, JE; Iwasaki, A	CD301b(+) Dermal Dendritic Cells Drive T Helper 2 Cell-Mediated Immunity		IMMUNITY		CD4(+) T-CELLS; TRANSCRIPTION FACTOR GATA-3; HELPER TYPE-2 RESPONSE; DUST MITE ALLERGEN; IN-VIVO; LANGERHANS CELLS; MUCOSAL IMMUNIZATION; AIRWAY INFLAMMATION; HELMINTH INFECTION; TH2 CELLS	Unlike other types of T helper (Th) responses, whether the development of Th2 cells requires instruction from particular subset of dendritic cells (DCs) remains unclear. By using an in vivo depletion approach, we have shown that DCs expressing CD301b were required for the generation of Th2 cells after subcutaneous immunization with ovalbumin (OVA) along with papain or alum. CD301b(+) DCs are distinct from epidermal or CD207(+) dermal DCs (DDCs) and were responsible for transporting antigen injected subcutaneously with Th2-type adjuvants. Transient depletion of CD301b(+) DCs resulted in less effective accumulation and decreased expression of CD69 by polyclonal CD4(+) T cells in the lymph node. Moreover, despite intact cell division and interferon-gamma production, CD301b(+) DC depletion led to blunted interleukin-4 production by OVA-specific OT-II transgenic CD4(+) T cells and significantly impaired Th2 cell development upon infection with Nippostrongylus brasiliensis. These results reveal CD301b(+) DDCs as the key mediators of Th2 immunity.	61	85	2013	11	10.1016/j.immuni.2013.08.029	Immunology
Air pollution ultrafine particles: toxicity beyond the lung. Background: Ultrafine particles or nanoparticles (UFPs or PM0.1) are the fraction of ambient particulates with an aerodynamic diameter smaller than 0.1 mu m. Currently UFPs are emerging as the most abundant particulate pollutants in urban and industrial areas, as their exposures have increased dramatically because of anthropogenic sources such as internal combustion engines, power plants, incinerators and many other sources of thermo-degradation. Ultrafine particles have been less studied than PM2.5 and PM10 particulates, mass concentrations of particles smaller than 2.5 and 10 mu m, respectively. Objective, Evidence and Information Sources: We examined the current scientific literature about the health effects of ultrafine particles exposure. State of the Art: UFPs are able to inhibit phagocytosis, and to stimulate inflammatory responses, damaging epithelial cells and potentially gaining access to the interstitium. They could be responsible for consistent reductions in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in patients with asthma. Chronic exposure to UFPs can produce deleterious effects on the lung, also causing oxidative stress and enhancing pro-inflammatory effects in airways of COPD patients. Cardiovascular detrimental consequences due to UFPs exposure have observed in epidemiological studies, and could likely be explained by translocation of UFPs from the respiratory epithelium towards circulation and subsequent toxicity to vascular endothelium; alteration of blood coagulation; triggering of autonomic nervous system reflexes eventually altering the cardiac frequency and function. Once deposited deeply into the lung, UFPs - in contrast to larger-sized particles - appear to access to the blood circulation by different transfer routes and mechanisms, resulting in distribution throughout the body, including the brain, with potential neurotoxic consequences. Perspectives and Conclusions. UFPs represent an area of toxicology of emerging concern. A new concept of environmental medicine would help in understanding not only the environmental mechanisms of disease, but also in developing specific preventive or therapeutic strategies for minimizing the dangerous influence of pollution on health.. nanoparticles| lung injury| cardiovascular disease| health effects|diesel exhaust particles| coronary-heart-disease| polycyclic aromatic-hydrocarbons| airborne particulate matter| long-term exposure| oxidative stress| fine particles| carbon-black| in-vivo| hospital admissions.	OCT-2010	nanoparticles| lung injury| cardiovascular disease| health effects|diesel exhaust particles| coronary-heart-disease| polycyclic aromatic-hydrocarbons| airborne particulate matter| long-term exposure| oxidative stress| fine particles| carbon-black| in-vivo| hospital admissions	Terzano, C; Di Stefano, F; Conti, V; Graziani, E; Petroianni, A	Air pollution ultrafine particles: toxicity beyond the lung		EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES	Nanoparticles; Lung injury; Cardiovascular disease; Health effects	DIESEL EXHAUST PARTICLES; CORONARY-HEART-DISEASE; POLYCYCLIC AROMATIC-HYDROCARBONS; AIRBORNE PARTICULATE MATTER; LONG-TERM EXPOSURE; OXIDATIVE STRESS; FINE PARTICLES; CARBON-BLACK; IN-VIVO; HOSPITAL ADMISSIONS	Background: Ultrafine particles or nanoparticles (UFPs or PM0.1) are the fraction of ambient particulates with an aerodynamic diameter smaller than 0.1 mu m. Currently UFPs are emerging as the most abundant particulate pollutants in urban and industrial areas, as their exposures have increased dramatically because of anthropogenic sources such as internal combustion engines, power plants, incinerators and many other sources of thermo-degradation. Ultrafine particles have been less studied than PM2.5 and PM10 particulates, mass concentrations of particles smaller than 2.5 and 10 mu m, respectively. Objective, Evidence and Information Sources: We examined the current scientific literature about the health effects of ultrafine particles exposure. State of the Art: UFPs are able to inhibit phagocytosis, and to stimulate inflammatory responses, damaging epithelial cells and potentially gaining access to the interstitium. They could be responsible for consistent reductions in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) in patients with asthma. Chronic exposure to UFPs can produce deleterious effects on the lung, also causing oxidative stress and enhancing pro-inflammatory effects in airways of COPD patients. Cardiovascular detrimental consequences due to UFPs exposure have observed in epidemiological studies, and could likely be explained by translocation of UFPs from the respiratory epithelium towards circulation and subsequent toxicity to vascular endothelium; alteration of blood coagulation; triggering of autonomic nervous system reflexes eventually altering the cardiac frequency and function. Once deposited deeply into the lung, UFPs - in contrast to larger-sized particles - appear to access to the blood circulation by different transfer routes and mechanisms, resulting in distribution throughout the body, including the brain, with potential neurotoxic consequences. Perspectives and Conclusions. UFPs represent an area of toxicology of emerging concern. A new concept of environmental medicine would help in understanding not only the environmental mechanisms of disease, but also in developing specific preventive or therapeutic strategies for minimizing the dangerous influence of pollution on health.	119	85	2010	13		Pharmacology & Pharmacy
Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice. To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F. IX. Whereas only 20-25% of control animals survived after six to eight F. IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F. IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F. IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 mu g recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (similar to 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.. allergy| chloroplast| genetic disorders| oral tolerance| plant-made therapeutics|heat-labile enterotoxin| cholera-toxin| transgenic chloroplasts| functional-evaluation| tobacco chloroplasts| escherichia-coli| vaccine antigens| immune-responses| gene-therapy| mouse model.	APR 13-2010	allergy| chloroplast| genetic disorders| oral tolerance| plant-made therapeutics|heat-labile enterotoxin| cholera-toxin| transgenic chloroplasts| functional-evaluation| tobacco chloroplasts| escherichia-coli| vaccine antigens| immune-responses| gene-therapy| mouse model	Verma, D; Moghimi, B; LoDuca, PA; Singh, HD; Hoffman, BE; Herzog, RW; Daniell, H	Oral delivery of bioencapsulated coagulation factor IX prevents inhibitor formation and fatal anaphylaxis in hemophilia B mice		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	allergy; chloroplast; genetic disorders; oral tolerance; plant-made therapeutics	HEAT-LABILE ENTEROTOXIN; CHOLERA-TOXIN; TRANSGENIC CHLOROPLASTS; FUNCTIONAL-EVALUATION; TOBACCO CHLOROPLASTS; ESCHERICHIA-COLI; VACCINE ANTIGENS; IMMUNE-RESPONSES; GENE-THERAPY; MOUSE MODEL	To address complications of pathogenic antibody or life-threatening anaphylactic reactions in protein replacement therapy for patients with hemophilia or other inherited protein deficiencies, we have developed a prophylactic protocol using a murine hemophilia B model. Oral delivery of coagulation factor IX fused with cholera toxin beta-subunit (with or without a furin cleavage site; CTB-FFIX or CTB-FIX), expressed in chloroplasts (up to 3.8% soluble protein or 0.4 mg/g leaf tissue), bioencapsulated in plant cells, effectively blocked formation of inhibitory antibodies (undetectable or up to 100-fold less than controls). Moreover, this treatment eliminated fatal anaphylactic reactions that occurred after four to six exposures to intravenous F. IX. Whereas only 20-25% of control animals survived after six to eight F. IX doses, 90-93% of F.IX-fed mice survived 12 injections without signs of allergy or anaphylaxis. Immunostaining confirmed delivery of F. IX to Peyer's patches in the ileum. Within 2-5 h, feeding of CTB-FFIX additionally resulted in systemic delivery of F. IX antigen. This high-responder strain of hemophilia B mice represents a new animal model to study anaphylactic reactions. The protocol was effective over a range of oral antigen doses (equivalent to 5-80 mu g recombinant F.IX/kg), and controlled inhibitor formation and anaphylaxis long-term, up to 7 months (similar to 40% life span of this mouse strain). Oral antigen administration caused a deviant immune response that suppressed formation of IgE and inhibitory antibodies. This cost-effective and efficient approach of antigen delivery to the gut should be applicable to several genetic diseases that are prone to pathogenic antibody responses during treatment.	41	85	2010	6	10.1073/pnas.0912181107	Science & Technology - Other Topics
Effect of Reducing Indoor Air Pollution on Women's Respiratory Symptoms and Lung Function: The RESPIRE Randomized Trial, Guatemala. Exposure to household wood smoke from cooking is a risk factor for chronic obstructive lung disease among women in developing countries. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) is a randomized intervention trial evaluating the respiratory health effects of reducing indoor air pollution from open cooking fires. A total of 504 rural Mayan women in highland Guatemala aged 15-50 years, all using traditional indoor open fires, were randomized to either receive a chimney woodstove (plancha) or continue using the open fire. Assessments of chronic respiratory symptoms and lung function and individual measurements of carbon monoxide exposure were performed at baseline and every 6 months up to 18 months. Use of a plancha significantly reduced carbon monoxide exposure by 61.6%. For all respiratory symptoms, reductions in risk were observed in the plancha group during follow-up; the reduction was statistically significant for wheeze (relative risk = 0.42, 95% confidence interval: 0.25, 0.70). The number of respiratory symptoms reported by the women at each follow-up point was also significantly reduced by the plancha (odds ratio = 0.7, 95% confidence interval: 0.50, 0.97). However, no significant effects on lung function were found after 12-18 months. Reducing indoor air pollution from household biomass burning may relieve symptoms consistent with chronic respiratory tract irritation.. biomass| bronchitis| chronic| carbon monoxide| developing countries| pulmonary disease| chronic obstructive| smoke| spirometry| wood|obstructive pulmonary-disease| wood smoke exposure| particulate matter| carbon-monoxide| highland guatemala| stove intervention| biomass smoke| mexican women| asthma| risk.	JUL 15-2009	biomass| bronchitis| chronic| carbon monoxide| developing countries| pulmonary disease| chronic obstructive| smoke| spirometry| wood|obstructive pulmonary-disease| wood smoke exposure| particulate matter| carbon-monoxide| highland guatemala| stove intervention| biomass smoke| mexican women| asthma| risk	Smith-Sivertsen, T; Diaz, E; Pope, D; Lie, RT; Diaz, A; McCracken, J; Bakke, P; Arana, B; Smith, KR; Bruce, N	Effect of Reducing Indoor Air Pollution on Women's Respiratory Symptoms and Lung Function: The RESPIRE Randomized Trial, Guatemala		AMERICAN JOURNAL OF EPIDEMIOLOGY	biomass; bronchitis; chronic; carbon monoxide; developing countries; pulmonary disease; chronic obstructive; smoke; spirometry; wood	OBSTRUCTIVE PULMONARY-DISEASE; WOOD SMOKE EXPOSURE; PARTICULATE MATTER; CARBON-MONOXIDE; HIGHLAND GUATEMALA; STOVE INTERVENTION; BIOMASS SMOKE; MEXICAN WOMEN; ASTHMA; RISK	Exposure to household wood smoke from cooking is a risk factor for chronic obstructive lung disease among women in developing countries. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) is a randomized intervention trial evaluating the respiratory health effects of reducing indoor air pollution from open cooking fires. A total of 504 rural Mayan women in highland Guatemala aged 15-50 years, all using traditional indoor open fires, were randomized to either receive a chimney woodstove (plancha) or continue using the open fire. Assessments of chronic respiratory symptoms and lung function and individual measurements of carbon monoxide exposure were performed at baseline and every 6 months up to 18 months. Use of a plancha significantly reduced carbon monoxide exposure by 61.6%. For all respiratory symptoms, reductions in risk were observed in the plancha group during follow-up; the reduction was statistically significant for wheeze (relative risk = 0.42, 95% confidence interval: 0.25, 0.70). The number of respiratory symptoms reported by the women at each follow-up point was also significantly reduced by the plancha (odds ratio = 0.7, 95% confidence interval: 0.50, 0.97). However, no significant effects on lung function were found after 12-18 months. Reducing indoor air pollution from household biomass burning may relieve symptoms consistent with chronic respiratory tract irritation.	44	85	2009	10	10.1093/aje/kwp100	Public, Environmental & Occupational Health
Air pollutants, oxidative stress and human health. Air pollutants have, and continue to be, major contributing factors to chronic diseases and mortality, subsequently impacting public health. Chronic diseases include: chronic obstructive pulmonary diseases (COPD), cardiovascular diseases (CVD), asthma, and cancer. Byproducts of oxidative stress found in air pollutants are common initiators or promoters of the damage produced in such chronic diseases. Such air pollutants include: ozone, sulfur oxides, carbon monoxide, nitrogen oxides, and particulate matter. Interaction between oxidative stress byproducts and certain genes within our population may modulate the expression of specific chronic diseases. in this brief review we attempt to provide some insight into what we currently know about the health problems associated with various air pollutants and their relationship in promoting chronic diseases through changes in oxidative stress and modulation of gene expression. Such insight eventually may direct the means for effective public health prevention and treatment of diseases associated with air pollution and treatment of diseases associated with air pollution. (C) 2008 Elsevier B.V. All rights reserved.. air pollution| oxidative stress| free radicals| human health| antioxidants|obstructive pulmonary-disease| inhaled nitrogen-dioxide| microsomal epoxide hydrolase| emergency room admissions| congestive-heart-failure| carbon-monoxide levels| hospital admissions| lung-cancer| daily mortality| ambient air.	MAR 31-2009	air pollution| oxidative stress| free radicals| human health| antioxidants|obstructive pulmonary-disease| inhaled nitrogen-dioxide| microsomal epoxide hydrolase| emergency room admissions| congestive-heart-failure| carbon-monoxide levels| hospital admissions| lung-cancer| daily mortality| ambient air	Yang, W; Omaye, ST	Air pollutants, oxidative stress and human health		MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS	Air pollution; Oxidative stress; Free radicals; Human health; Antioxidants	OBSTRUCTIVE PULMONARY-DISEASE; INHALED NITROGEN-DIOXIDE; MICROSOMAL EPOXIDE HYDROLASE; EMERGENCY ROOM ADMISSIONS; CONGESTIVE-HEART-FAILURE; CARBON-MONOXIDE LEVELS; HOSPITAL ADMISSIONS; LUNG-CANCER; DAILY MORTALITY; AMBIENT AIR	Air pollutants have, and continue to be, major contributing factors to chronic diseases and mortality, subsequently impacting public health. Chronic diseases include: chronic obstructive pulmonary diseases (COPD), cardiovascular diseases (CVD), asthma, and cancer. Byproducts of oxidative stress found in air pollutants are common initiators or promoters of the damage produced in such chronic diseases. Such air pollutants include: ozone, sulfur oxides, carbon monoxide, nitrogen oxides, and particulate matter. Interaction between oxidative stress byproducts and certain genes within our population may modulate the expression of specific chronic diseases. in this brief review we attempt to provide some insight into what we currently know about the health problems associated with various air pollutants and their relationship in promoting chronic diseases through changes in oxidative stress and modulation of gene expression. Such insight eventually may direct the means for effective public health prevention and treatment of diseases associated with air pollution and treatment of diseases associated with air pollution. (C) 2008 Elsevier B.V. All rights reserved.	123	85	2009	10	10.1016/j.mrgentox.2008.10.005	Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
"Determinants of allergenicity. The question ""What makes an allergen an allergen?"" has puzzled generations of researchers, and we still do not have a conclusive answer. Despite increasing knowledge about the molecular and functional characteristics of allergens that have been identified, we still do not fully understand why some proteins are clinically relevant allergens and most are not. Different approaches have been taken to identify the structural and functional features of allergens, aiming at developing methods to predict allergenicity and thus to identify allergens. However, none of these methods has allowed a reliable discrimination between allergenic and nonallergenic compounds on its own. This review sums up diverse determinants that contribute to the phenomenon of allergenicity and outlines that in addition to the structure and function of the allergen, factors derived from allergen carriers, the environment, and the susceptible individual are of importance. (J Allergy Clin Immunol 2009;123:558-66.). allergen| structure| intrinsic function| pollen-associated lipid mediators| adjuvant|house-dust mite| serum ige levels| allergic airway inflammation| cysteine protease activity| diesel exhaust particles| cd4(+)cd25(+) t-cells| amino-acid-sequence| der-p-i| dendritic cells| proteolytic activity."	MAR-2009	allergen| structure| intrinsic function| pollen-associated lipid mediators| adjuvant|house-dust mite| serum ige levels| allergic airway inflammation| cysteine protease activity| diesel exhaust particles| cd4(+)cd25(+) t-cells| amino-acid-sequence| der-p-i| dendritic cells| proteolytic activity	Traidl-Hoffmann, C; Jakob, T; Behrendt, H	Determinants of allergenicity		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergen; structure; intrinsic function; pollen-associated lipid mediators; adjuvant	HOUSE-DUST MITE; SERUM IGE LEVELS; ALLERGIC AIRWAY INFLAMMATION; CYSTEINE PROTEASE ACTIVITY; DIESEL EXHAUST PARTICLES; CD4(+)CD25(+) T-CELLS; AMINO-ACID-SEQUENCE; DER-P-I; DENDRITIC CELLS; PROTEOLYTIC ACTIVITY	"The question ""What makes an allergen an allergen?"" has puzzled generations of researchers, and we still do not have a conclusive answer. Despite increasing knowledge about the molecular and functional characteristics of allergens that have been identified, we still do not fully understand why some proteins are clinically relevant allergens and most are not. Different approaches have been taken to identify the structural and functional features of allergens, aiming at developing methods to predict allergenicity and thus to identify allergens. However, none of these methods has allowed a reliable discrimination between allergenic and nonallergenic compounds on its own. This review sums up diverse determinants that contribute to the phenomenon of allergenicity and outlines that in addition to the structure and function of the allergen, factors derived from allergen carriers, the environment, and the susceptible individual are of importance. (J Allergy Clin Immunol 2009;123:558-66.)"	122	85	2009	9	10.1016/j.jaci.2008.12.003	Allergy; Immunology
"Allergen immunotherapy: A practice parameter second update. These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing the ""Allergen immunotherapy: a practice parameter second update."" This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.. grass-pollen immunotherapy| house-dust-mite| dermatophagoides-pteronyssinus extract| placebo-controlled trial| sublingual-swallow immunotherapy| double-blind placebo| standardized cat extract| imported fire ant| local nasal immunotherapy| insect sting allergy."	SEP-2007	grass-pollen immunotherapy| house-dust-mite| dermatophagoides-pteronyssinus extract| placebo-controlled trial| sublingual-swallow immunotherapy| double-blind placebo| standardized cat extract| imported fire ant| local nasal immunotherapy| insect sting allergy	Cox, L; Li, JT; Nelson, H; Lockey, R	Allergen immunotherapy: A practice parameter second update		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY		GRASS-POLLEN IMMUNOTHERAPY; HOUSE-DUST-MITE; DERMATOPHAGOIDES-PTERONYSSINUS EXTRACT; PLACEBO-CONTROLLED TRIAL; SUBLINGUAL-SWALLOW IMMUNOTHERAPY; DOUBLE-BLIND PLACEBO; STANDARDIZED CAT EXTRACT; IMPORTED FIRE ANT; LOCAL NASAL IMMUNOTHERAPY; INSECT STING ALLERGY	"These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing the ""Allergen immunotherapy: a practice parameter second update."" This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or the ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion."	349	85	2007	61	10.1016/j.jaci.2007.06.019	Allergy; Immunology
Cigarette smoke drives small airway remodeling by induction of growth factors in the airway wall. Background: Small airway remodeling (SAR) is an important cause of airflow obstruction in cigarette smokers with chronic obstructive pulmonary disease, but the pathogenesis of SAR is not understood. Objective: To determine whether smoke causes production of profibrotic growth factors in the airway wall. Methods: We exposed C57BI/6 mice to cigarette smoke for up to 6 mo and examined growth factor/procollagen gene expression in laser-capture microdissected small airways by real-time reverse transcription-polymerase chain reaction. Results: With a single smoke exposure, increases in procollagen, connective tissue growth factor (CTGF), transforming growth factor (TGF)-beta(1), platelet-derived growth factor (PDGF)-A and -B expression were seen 2 h after the start of smoking and declined to baseline by 24 h. With repeated exposures and at killing of animals 24 h after the last exposure, increases in procollagen, CTGF, PDGF-B, and (minimally) PDGF-A expression persisted through 1 wk, 1 mo, and 6 mo. TGF-beta(1) gene expression declined over time; however, increased immunochemical staining for phopho-Smad 2 was present at all time points, indicating continuing TGF-beta downstream signaling. Morphometric analysis showed that the small airways in smoke-exposed mice had more Collagen at 6 mo. Conclusions: These findings suggest that smoke can induce growth factor and procollagen production in small airways in a time frame that initially is too short for a significant inflammatory response and that profibrotic growth factor and procollagen gene expression become self-sustaining with repeated smoke exposures. These results imply that the pathogenesis of and possible treatment approaches to emphysema and small airway remodeling might be quite different.. cigarette smoke| connective tissue growth factor| platelet-derived growth factor| small airway remodeling| transforming growth factor-beta|obstructive pulmonary-disease| transforming growth-factor-beta-1| factor beta(1)| fibrosis| lung| expression| asthma| model| activation| cells.	DEC 15-2006	cigarette smoke| connective tissue growth factor| platelet-derived growth factor| small airway remodeling| transforming growth factor-beta|obstructive pulmonary-disease| transforming growth-factor-beta-1| factor beta(1)| fibrosis| lung| expression| asthma| model| activation| cells	Churg, A; Tai, H; Coulthard, T; Wang, R; Wright, JL	Cigarette smoke drives small airway remodeling by induction of growth factors in the airway wall		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	cigarette smoke; connective tissue growth factor; platelet-derived growth factor; small airway remodeling; transforming growth factor-beta	OBSTRUCTIVE PULMONARY-DISEASE; TRANSFORMING GROWTH-FACTOR-BETA-1; FACTOR BETA(1); FIBROSIS; LUNG; EXPRESSION; ASTHMA; MODEL; ACTIVATION; CELLS	Background: Small airway remodeling (SAR) is an important cause of airflow obstruction in cigarette smokers with chronic obstructive pulmonary disease, but the pathogenesis of SAR is not understood. Objective: To determine whether smoke causes production of profibrotic growth factors in the airway wall. Methods: We exposed C57BI/6 mice to cigarette smoke for up to 6 mo and examined growth factor/procollagen gene expression in laser-capture microdissected small airways by real-time reverse transcription-polymerase chain reaction. Results: With a single smoke exposure, increases in procollagen, connective tissue growth factor (CTGF), transforming growth factor (TGF)-beta(1), platelet-derived growth factor (PDGF)-A and -B expression were seen 2 h after the start of smoking and declined to baseline by 24 h. With repeated exposures and at killing of animals 24 h after the last exposure, increases in procollagen, CTGF, PDGF-B, and (minimally) PDGF-A expression persisted through 1 wk, 1 mo, and 6 mo. TGF-beta(1) gene expression declined over time; however, increased immunochemical staining for phopho-Smad 2 was present at all time points, indicating continuing TGF-beta downstream signaling. Morphometric analysis showed that the small airways in smoke-exposed mice had more Collagen at 6 mo. Conclusions: These findings suggest that smoke can induce growth factor and procollagen production in small airways in a time frame that initially is too short for a significant inflammatory response and that profibrotic growth factor and procollagen gene expression become self-sustaining with repeated smoke exposures. These results imply that the pathogenesis of and possible treatment approaches to emphysema and small airway remodeling might be quite different.	43	85	2006	8	10.1164/rccm.200605-585OC	General & Internal Medicine; Respiratory System
Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis?. House dust mite (HDM) allergens are perennial indoor allergens, which may play a role as allergic trigger factors in atopic dermatitis (AD). Facilitated by their high enzymatic activity, HDM allergens are capable of penetrating the impaired epidermal skin barrier in patients with AD, gaining access to immune cells. In this way, HDM allergens induce both allergic reactions of the immediate type and allergic reactions of the delayed type, which contribute to impairment of AD. Because allergen reduction achieved by encasing strategies does not always lead to significant improvement of clinical symptoms, specific immunotherapy (SIT) might represent an attractive therapeutic option for long-time treatment of this subgroup of patients with AD. However, systematic studies on the effectiveness of SIT in patients with AD are rare. Furthermore, data on the immunologic changes induced by SIT in patients with AD are not well studied. In this review, we provide an overview of the pathogenic impact of HDM allergens as an example for aeroallergens on the course of AD. In addition, we discuss prophylactic and therapeutic options for the treatment of HDM allergy in patients with AD, including a summary of the current data available on SIT as a potential therapeutic option for patients with AD.. allergy| atopic dermatitis| house dust mite| allergen specific immunotherapy|house-dust-mite| blind controlled trial| dermatophagoides-pteronyssinus| sublingual immunotherapy| asthmatic-patients| hyposensitization| children| rhinitis| immunology| avoidance.	DEC-2006	allergy| atopic dermatitis| house dust mite| allergen specific immunotherapy|house-dust-mite| blind controlled trial| dermatophagoides-pteronyssinus| sublingual immunotherapy| asthmatic-patients| hyposensitization| children| rhinitis| immunology| avoidance	Bussmann, C; Bockenhoff, A; Henke, H; Werfel, T; Novak, N	Does allergen-specific immunotherapy represent a therapeutic option for patients with atopic dermatitis?		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	allergy; atopic dermatitis; house dust mite; allergen specific immunotherapy	HOUSE-DUST-MITE; BLIND CONTROLLED TRIAL; DERMATOPHAGOIDES-PTERONYSSINUS; SUBLINGUAL IMMUNOTHERAPY; ASTHMATIC-PATIENTS; HYPOSENSITIZATION; CHILDREN; RHINITIS; IMMUNOLOGY; AVOIDANCE	House dust mite (HDM) allergens are perennial indoor allergens, which may play a role as allergic trigger factors in atopic dermatitis (AD). Facilitated by their high enzymatic activity, HDM allergens are capable of penetrating the impaired epidermal skin barrier in patients with AD, gaining access to immune cells. In this way, HDM allergens induce both allergic reactions of the immediate type and allergic reactions of the delayed type, which contribute to impairment of AD. Because allergen reduction achieved by encasing strategies does not always lead to significant improvement of clinical symptoms, specific immunotherapy (SIT) might represent an attractive therapeutic option for long-time treatment of this subgroup of patients with AD. However, systematic studies on the effectiveness of SIT in patients with AD are rare. Furthermore, data on the immunologic changes induced by SIT in patients with AD are not well studied. In this review, we provide an overview of the pathogenic impact of HDM allergens as an example for aeroallergens on the course of AD. In addition, we discuss prophylactic and therapeutic options for the treatment of HDM allergy in patients with AD, including a summary of the current data available on SIT as a potential therapeutic option for patients with AD.	60	85	2006	7	10.1016/j.jaci.2006.07.054	Allergy; Immunology
Trends in prevalence of asthma, allergic rhinitis and atopic dermatitis in 5-7-year old Swiss children from 1992 to 2001. Background: Changing occurrence rates of asthma, allergic rhinitis and atopic dermatitis are of public health concern and require surveillance. Changes in prevalence rates of these atopic diseases were monitored during 10 years and their trend with time was determined taking into account the influence of personal and environmental risk factors. Methods: Four cross-sectional surveys in 5-7-year old children were performed in seven different communities in Switzerland between 1992 and 2001. Prevalence of respiratory and allergic symptoms and of affecting risk factors including parental environmental concern were assessed using a standardized parental questionnaire. Results: A total of 988 (74.1%), 1778 (79.0%), 1406 (82.6%) and 1274 (78.9%) children participated, respectively, in the 1992, 1995, 1998 and 2001 surveys. Prevalence rates of asthma and hay fever symptoms remained quite stable over time (wheeze/past year: 8.8%, 7.8%, 6.4% and 7.4%, sneezing attack during pollen season: 5.0%, 5.6%, 5.4% and 4.6%). Rates of reported atopic dermatitis symptoms (specific skin rash/past year: 4.6%, 6.5%,7.4% and 7.6%) showed an increase over time, but those of diagnosis of eczema did not show a clear pattern (18.4%, 15.7%, 14.0% and 15.2%). Stratified analysis by parental environmental concern and by parental atopy showed similar trends. Rates of atopic dermatitis symptoms showed significant increase in girls but stayed stable in boys. Conclusion: Results of these four consecutive surveys suggest that the increase in prevalence of asthma and hay fever in 5-7-year old children living in Switzerland may have ceased. However, symptoms of atopic dermatitis may still be on the rise, especially among girls.. allergic rhinitis| asthma| atopic dermatitis| children| trend|isaac phase-i| increasing prevalence| respiratory health| air-pollution| hay-fever| hong-kong| schoolchildren| adolescents| childhood| germany.	MAR-2006	allergic rhinitis| asthma| atopic dermatitis| children| trend|isaac phase-i| increasing prevalence| respiratory health| air-pollution| hay-fever| hong-kong| schoolchildren| adolescents| childhood| germany	Grize, L; Gassner, M; Wuthrich, B; Bringolf-Isler, B; Takken-Sahli, K; Sennhauser, FH; Stricker, T; Eigenmann, PA; Braun-Fahrlander, C	Trends in prevalence of asthma, allergic rhinitis and atopic dermatitis in 5-7-year old Swiss children from 1992 to 2001		ALLERGY	allergic rhinitis; asthma; atopic dermatitis; children; trend	ISAAC PHASE-I; INCREASING PREVALENCE; RESPIRATORY HEALTH; AIR-POLLUTION; HAY-FEVER; HONG-KONG; SCHOOLCHILDREN; ADOLESCENTS; CHILDHOOD; GERMANY	Background: Changing occurrence rates of asthma, allergic rhinitis and atopic dermatitis are of public health concern and require surveillance. Changes in prevalence rates of these atopic diseases were monitored during 10 years and their trend with time was determined taking into account the influence of personal and environmental risk factors. Methods: Four cross-sectional surveys in 5-7-year old children were performed in seven different communities in Switzerland between 1992 and 2001. Prevalence of respiratory and allergic symptoms and of affecting risk factors including parental environmental concern were assessed using a standardized parental questionnaire. Results: A total of 988 (74.1%), 1778 (79.0%), 1406 (82.6%) and 1274 (78.9%) children participated, respectively, in the 1992, 1995, 1998 and 2001 surveys. Prevalence rates of asthma and hay fever symptoms remained quite stable over time (wheeze/past year: 8.8%, 7.8%, 6.4% and 7.4%, sneezing attack during pollen season: 5.0%, 5.6%, 5.4% and 4.6%). Rates of reported atopic dermatitis symptoms (specific skin rash/past year: 4.6%, 6.5%,7.4% and 7.6%) showed an increase over time, but those of diagnosis of eczema did not show a clear pattern (18.4%, 15.7%, 14.0% and 15.2%). Stratified analysis by parental environmental concern and by parental atopy showed similar trends. Rates of atopic dermatitis symptoms showed significant increase in girls but stayed stable in boys. Conclusion: Results of these four consecutive surveys suggest that the increase in prevalence of asthma and hay fever in 5-7-year old children living in Switzerland may have ceased. However, symptoms of atopic dermatitis may still be on the rise, especially among girls.	29	85	2006	7	10.1111/j.1398-9995.2006.01030.x	Allergy; Immunology
Environmental equity, air quality, socioeconomic status, and respiratory health: a linkage analysis of routine data from the Health Survey for England. Study objective: To assess relations between socioeconomic status and local air quality, and combined effects on respiratory health, in the context of environmental and health inequality. Design: Data on people taking part in the Health Survey for England were attributed with a small area index of air pollution using annual mean concentrations of nitrogen dioxide, sulphur dioxide, benzene, and particulates (PM10). Regression models were used to measure associations between social class, air quality, forced expiratory volume in one second (FEV1), and self reported asthma. Participants: Participants aged 16 - 79 in the Health Survey for England 1995, 1996, and 1997. Main results: Urban lower social class households were more likely to be located in areas of poor air quality, but the association in rural areas was, if anything reversed. Low social class and poor air quality were independently associated with decreased lung function (FEV1), but not asthma prevalence, after adjustment for a number of potential confounders. Social class effects were not attenuated by adjustment for air quality. In men, a differential effect of air pollution on FEV1 was found, with its effect in social classes III to V about double that in social classes I and II ( p value for interaction = 0.04). This effect modification was not seen for women. Conclusions: Further evidence of environmental inequity in the UK is provided. The association between FEV1 and local air quality is of similar magnitude to that with social class, and the adverse effects of air pollution seem to be greater in men in lower social classes.. pollution| justice| asthma| association| mortality| exposure| cohort.	NOV-2005	pollution| justice| asthma| association| mortality| exposure| cohort	Wheeler, BW; Ben-Shlomo, Y	Environmental equity, air quality, socioeconomic status, and respiratory health: a linkage analysis of routine data from the Health Survey for England		JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH		POLLUTION; JUSTICE; ASTHMA; ASSOCIATION; MORTALITY; EXPOSURE; COHORT	Study objective: To assess relations between socioeconomic status and local air quality, and combined effects on respiratory health, in the context of environmental and health inequality. Design: Data on people taking part in the Health Survey for England were attributed with a small area index of air pollution using annual mean concentrations of nitrogen dioxide, sulphur dioxide, benzene, and particulates (PM10). Regression models were used to measure associations between social class, air quality, forced expiratory volume in one second (FEV1), and self reported asthma. Participants: Participants aged 16 - 79 in the Health Survey for England 1995, 1996, and 1997. Main results: Urban lower social class households were more likely to be located in areas of poor air quality, but the association in rural areas was, if anything reversed. Low social class and poor air quality were independently associated with decreased lung function (FEV1), but not asthma prevalence, after adjustment for a number of potential confounders. Social class effects were not attenuated by adjustment for air quality. In men, a differential effect of air pollution on FEV1 was found, with its effect in social classes III to V about double that in social classes I and II ( p value for interaction = 0.04). This effect modification was not seen for women. Conclusions: Further evidence of environmental inequity in the UK is provided. The association between FEV1 and local air quality is of similar magnitude to that with social class, and the adverse effects of air pollution seem to be greater in men in lower social classes.	37	85	2005	7	10.1136/jech.2005.036418	Public, Environmental & Occupational Health
Protein nitration by polluted air. The effects of air pollution on allergic diseases are not yet well-understood. Here, we show that proteins, in particular birch pollen proteins including the allergen Bet v 1, are efficiently nitrated by polluted air. This posttranslational modification of proteins is likely to trigger immune reactions and provides a molecular rationale for the promotion of allergies by traffic-related air pollution. Enzyme immunoassays have been used to determine equivalent degrees of nitration (EDN) for protein samples exposed to urban outdoor air and synthetic gas mixtures. The observed rates of nitration were governed by the abundance of nitrogen oxides and ozone, and concentration levels typical for summer smog conditions led to substantial nitration within a few hours to days (EDN up to 20%). Moreover, nitrated proteins were detected in urban road dust, window dust, and fine air particulate matter (EDN up to 0.1%).. polycyclic aromatic-hydrocarbons| bet v 1| liquid-chromatography| particulate matter| aqueous-solution| fine particles| grass-pollen| allergens| ige| gas.	MAR 15-2005	polycyclic aromatic-hydrocarbons| bet v 1| liquid-chromatography| particulate matter| aqueous-solution| fine particles| grass-pollen| allergens| ige| gas	Franze, T; Weller, MG; Niessner, R; Poschl, U	Protein nitration by polluted air		ENVIRONMENTAL SCIENCE & TECHNOLOGY		POLYCYCLIC AROMATIC-HYDROCARBONS; BET V 1; LIQUID-CHROMATOGRAPHY; PARTICULATE MATTER; AQUEOUS-SOLUTION; FINE PARTICLES; GRASS-POLLEN; ALLERGENS; IGE; GAS	The effects of air pollution on allergic diseases are not yet well-understood. Here, we show that proteins, in particular birch pollen proteins including the allergen Bet v 1, are efficiently nitrated by polluted air. This posttranslational modification of proteins is likely to trigger immune reactions and provides a molecular rationale for the promotion of allergies by traffic-related air pollution. Enzyme immunoassays have been used to determine equivalent degrees of nitration (EDN) for protein samples exposed to urban outdoor air and synthetic gas mixtures. The observed rates of nitration were governed by the abundance of nitrogen oxides and ozone, and concentration levels typical for summer smog conditions led to substantial nitration within a few hours to days (EDN up to 20%). Moreover, nitrated proteins were detected in urban road dust, window dust, and fine air particulate matter (EDN up to 0.1%).	46	85	2005	6	10.1021/es0488737	Engineering; Environmental Sciences & Ecology
CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge. T-helper (Th) 2 cytokines; are thought to mediate most features of allergic inflammation in atopic asthma. However, it remains unclear whether chemokine pathways direct selective recruitment of Th2 cells to the airways during human allergic responses. Bronchoalveolar lavage (BAL) was performed in 15 nonsmoking mild atopic asthmatics before and 24 h after a fibreoptic segmental allergen challenge, and chemokines related to T-cell recruitment were assayed by ELISA. The Th2-related C-C chemokine (CCR)4 ligands, macrophage-derived chemokine/C-C chemokine ligand (CCL)22 and thymus and activation-regulated chemokine/CCL17, were increased in BAL after challenge. These chemokines correlated significantly with lymphocyte numbers and with interleukin (IL)-5 and IL-13 in post-challenge B L. In contrast, two out of three putative Th1-related chemokines; did not change. There were no alterations in monokine induced by interferon (IFN)-gamma/CXC chemokine ligand (CXCL)9 or macrophage inflammatory protein-1alpha/CCL3; whereas a significant increase in IFN-induced protein-10kDa/CXCL 10 was observed, which did not correlate with the T-cell influx. In peripheral mononuclear cells from atopic donors, CCL22 and CCL17 were induced by IL-4 and IL-13, further supporting the relationship between CCL22/CCL17 and Th2 cytokines. Finally, CCL22 was able to trigger actin polymerisation in peripheral CD4+ T-cells expressing CCR4. Thus, C-C chemokine receptor 4 ligands are up-regulated in the airways of atopic asthmatics following allergen exposure, contribute to the T-cell influx to the airways and are closely related to the Th2-cytokine response.. allergen challenge| asthma| c-c chemokine receptor 4| chemokines| cytokines|bronchial epithelial-cells| chemokine receptor cxcr3| t-cells| in-vivo| th2 cells| bronchoalveolar lavage| respiratory-disease| expression| lymphocytes| lung.	JUN-2004	allergen challenge| asthma| c-c chemokine receptor 4| chemokines| cytokines|bronchial epithelial-cells| chemokine receptor cxcr3| t-cells| in-vivo| th2 cells| bronchoalveolar lavage| respiratory-disease| expression| lymphocytes| lung	Pilette, C; Francis, JN; Till, SJ; Durham, SR	CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge		EUROPEAN RESPIRATORY JOURNAL	allergen challenge; asthma; C-C chemokine receptor 4; chemokines; cytokines	BRONCHIAL EPITHELIAL-CELLS; CHEMOKINE RECEPTOR CXCR3; T-CELLS; IN-VIVO; TH2 CELLS; BRONCHOALVEOLAR LAVAGE; RESPIRATORY-DISEASE; EXPRESSION; LYMPHOCYTES; LUNG	T-helper (Th) 2 cytokines; are thought to mediate most features of allergic inflammation in atopic asthma. However, it remains unclear whether chemokine pathways direct selective recruitment of Th2 cells to the airways during human allergic responses. Bronchoalveolar lavage (BAL) was performed in 15 nonsmoking mild atopic asthmatics before and 24 h after a fibreoptic segmental allergen challenge, and chemokines related to T-cell recruitment were assayed by ELISA. The Th2-related C-C chemokine (CCR)4 ligands, macrophage-derived chemokine/C-C chemokine ligand (CCL)22 and thymus and activation-regulated chemokine/CCL17, were increased in BAL after challenge. These chemokines correlated significantly with lymphocyte numbers and with interleukin (IL)-5 and IL-13 in post-challenge B L. In contrast, two out of three putative Th1-related chemokines; did not change. There were no alterations in monokine induced by interferon (IFN)-gamma/CXC chemokine ligand (CXCL)9 or macrophage inflammatory protein-1alpha/CCL3; whereas a significant increase in IFN-induced protein-10kDa/CXCL 10 was observed, which did not correlate with the T-cell influx. In peripheral mononuclear cells from atopic donors, CCL22 and CCL17 were induced by IL-4 and IL-13, further supporting the relationship between CCL22/CCL17 and Th2 cytokines. Finally, CCL22 was able to trigger actin polymerisation in peripheral CD4+ T-cells expressing CCR4. Thus, C-C chemokine receptor 4 ligands are up-regulated in the airways of atopic asthmatics following allergen exposure, contribute to the T-cell influx to the airways and are closely related to the Th2-cytokine response.	38	85	2004	9	10.1183/09031936.04.00102504	Respiratory System
Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice. Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthma-like responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-I mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 mug of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SIRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor a, macrophage inhibitory protein-2, and the T(H)2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 mug) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs.. automobile| diesel exhaust particles| forklift| mice| pulmonary toxicity| srm 2975|airway inflammation| ige production| emissions| particulate| exposure| health| hyperresponsiveness| mutagenicity| expression| components.	JUN-2004	automobile| diesel exhaust particles| forklift| mice| pulmonary toxicity| srm 2975|airway inflammation| ige production| emissions| particulate| exposure| health| hyperresponsiveness| mutagenicity| expression| components	Singh, P; DeMarini, DM; Dick, CAJ; Tabor, DG; Ryan, JV; Linak, WP; Kobayashi, T; Gilmour, MI	Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice		ENVIRONMENTAL HEALTH PERSPECTIVES	automobile; diesel exhaust particles; forklift; mice; pulmonary toxicity; SRM 2975	AIRWAY INFLAMMATION; IGE PRODUCTION; EMISSIONS; PARTICULATE; EXPOSURE; HEALTH; HYPERRESPONSIVENESS; MUTAGENICITY; EXPRESSION; COMPONENTS	Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthma-like responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-I mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 mug of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SIRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor a, macrophage inhibitory protein-2, and the T(H)2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 mug) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs.	36	85	2004	6	10.1289/ehp.6579	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Effects of a comprehensive self-management programme in patients with chronic obstructive pulmonary disease. The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life (HRQoL), symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease (COPD). This study was part of the overall COPD study of the Dept of Pulmonary Medicine, Enschede, which consisted of an inhaled corticosteroid (ICS) trial and a self-management trial. After the ICS trial, all patients were randomised again to a self-management and a control group. The self-management intervention consisted of a skill-oriented patient education programme and a near-home fitness programme, on top of usual care. The control group received usual care by the treating chest physician. HRQoL was measured by the St George's Respiratory Questionnaire (SGRQ) and walking distance by the 6-min walking test. Patients recorded their symptoms in diaries and graded their health status from 1-10 in a weekly report. Altogether, 248 COPD patients were randomly allocated to either an intervention (127) or control (121) group. No differences in the SGRQ scores within and between both groups were observed over I yr. Similarly, no differences in symptom scores and 6-min walking distance were found within and between groups. The intervention group reported more exacerbations than the control group. The majority (69%) of the exacerbations in the intervention group were self-treated at home. This study failed to show positive effects of a self-management programme among moderately severe chronic obstructive pulmonary disease patients.. chronic obstructive lung disease| patient education| quality of life| randomised controlled trial| self-management|quality-of-life| air-flow limitation| 6-minute walk test| fluticasone propionate| controlled trial| health-status| lung-disease| education| asthma| copd.	NOV-2003	chronic obstructive lung disease| patient education| quality of life| randomised controlled trial| self-management|quality-of-life| air-flow limitation| 6-minute walk test| fluticasone propionate| controlled trial| health-status| lung-disease| education| asthma| copd	Monninkhof, E; van der Valk, P; van der Palen, J; van Herwaarden, C; Zielhuis, G	Effects of a comprehensive self-management programme in patients with chronic obstructive pulmonary disease		EUROPEAN RESPIRATORY JOURNAL	chronic obstructive lung disease; patient education; quality of life; randomised controlled trial; self-management	QUALITY-OF-LIFE; AIR-FLOW LIMITATION; 6-MINUTE WALK TEST; FLUTICASONE PROPIONATE; CONTROLLED TRIAL; HEALTH-STATUS; LUNG-DISEASE; EDUCATION; ASTHMA; COPD	The aim of this study was to assess the effects of a comprehensive self-management intervention on health-related quality of life (HRQoL), symptoms and walking distance in patients with stable moderately severe chronic obstructive pulmonary disease (COPD). This study was part of the overall COPD study of the Dept of Pulmonary Medicine, Enschede, which consisted of an inhaled corticosteroid (ICS) trial and a self-management trial. After the ICS trial, all patients were randomised again to a self-management and a control group. The self-management intervention consisted of a skill-oriented patient education programme and a near-home fitness programme, on top of usual care. The control group received usual care by the treating chest physician. HRQoL was measured by the St George's Respiratory Questionnaire (SGRQ) and walking distance by the 6-min walking test. Patients recorded their symptoms in diaries and graded their health status from 1-10 in a weekly report. Altogether, 248 COPD patients were randomly allocated to either an intervention (127) or control (121) group. No differences in the SGRQ scores within and between both groups were observed over I yr. Similarly, no differences in symptom scores and 6-min walking distance were found within and between groups. The intervention group reported more exacerbations than the control group. The majority (69%) of the exacerbations in the intervention group were self-treated at home. This study failed to show positive effects of a self-management programme among moderately severe chronic obstructive pulmonary disease patients.	32	85	2003	6	10.1183/09031936.03.00047003	Respiratory System
Metal composition of ambient PM2.5 influences severity of allergic airways disease in mice. Children living in Hettstedt in eastern Germany have been reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst; these differences correlated with the presence of industrial air pollution. Samples of fine particulate matter (< 2.5 mum aerodynamic diameter; PM2.5) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM2.5 from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM2.5 from Hettstedt, but not PM2.5 from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Flettstedt PM2.5 whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only, in allergic mice exposed to Hettstedt PM2.5 before challenge. Both Hettstedt and Zerbst PM2.5 significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM, 5 influences the severity of allergic respiratory disease.. air pollution| airway hyperresponsiveness| allergic sensitization| asthma| epidemiology| inflammation| metals|oil fly-ash| house-dust mite| air-pollution| respiratory symptoms| pulmonary toxicity| interferon-gamma| utah valley| lung injury| sensitization| asthma.	SEP-2003	air pollution| airway hyperresponsiveness| allergic sensitization| asthma| epidemiology| inflammation| metals|oil fly-ash| house-dust mite| air-pollution| respiratory symptoms| pulmonary toxicity| interferon-gamma| utah valley| lung injury| sensitization| asthma	Gavett, SH; Haykal-Coates, N; Copeland, LB; Heinrich, J; Gilmour, MI	Metal composition of ambient PM2.5 influences severity of allergic airways disease in mice		ENVIRONMENTAL HEALTH PERSPECTIVES	air pollution; airway hyperresponsiveness; allergic sensitization; asthma; epidemiology; inflammation; metals	OIL FLY-ASH; HOUSE-DUST MITE; AIR-POLLUTION; RESPIRATORY SYMPTOMS; PULMONARY TOXICITY; INTERFERON-GAMMA; UTAH VALLEY; LUNG INJURY; SENSITIZATION; ASTHMA	Children living in Hettstedt in eastern Germany have been reported to have a higher prevalence of sensitization to common aeroallergens than another cohort living in the neighboring city of Zerbst; these differences correlated with the presence of industrial air pollution. Samples of fine particulate matter (< 2.5 mum aerodynamic diameter; PM2.5) collected in Hettstedt in 1999 had several-fold higher levels of zinc, magnesium, lead, copper, and cadmium than samples from Zerbst. To determine if the results from epidemiologic studies could be repeated in an animal model, we administered PM2.5 from Hettstedt and Zerbst to ovalbumin-allergic mice. In Balb/c mice, PM2.5 from Hettstedt, but not PM2.5 from Zerbst or control filter extract, caused a significant increase in immediate responses to ovalbumin challenge when aspirated 2 hr before challenge, but not when aspirated immediately before sensitization 2 weeks earlier. Antigen-specific IgE was increased by Flettstedt PM2.5 whether administered before sensitization or challenge. Airway responsiveness to methacholine aerosol and lung inflammatory cell numbers were significantly increased only, in allergic mice exposed to Hettstedt PM2.5 before challenge. Both Hettstedt and Zerbst PM2.5 significantly increased lung injury parameters and proinflammatory cytokines. These results are consistent with epidemiologic findings and show that metal composition of ambient PM, 5 influences the severity of allergic respiratory disease.	33	85	2003	7	10.1289/ehp.6300	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells. Human beta-defensins (hBDs) are antimicrobial peptides that play important roles in host defense against infection, inflammation and immunity. Previous studies showed that micro-organisms and proinflammatory mediators regulate the expression of these peptides in airway epithelial cells. The aim of the present study was to investigate the modulation of expression of hBDs in cultured primary bronchial epithelial cells (PBEC) by rhinovirus-16 (RV16), a respiratory virus responsible for the common cold and associated with asthma exacerbations. RV16 was found to induce expression of hBD-2 and -3 mRNA in PBEC, but did not affect hBD-1 mRNA. Viral replication appeared essential for rhinovirus-induced beta-defensin mRNA expression, since UV-inactivated rhinovirus did not increase expression of hBD-2 and hBD-3 mRNA. Exposure to synthetic double-stranded RNA (dsRNA) molecule polyinosinic:polycytidylic acid had a similar effect as RV16 on mRNA expression of these peptides in PBEC. In line with this, PBEC were found to express TLR3, a Toll-like receptor involved in recognition of dsRNA. This study shows that rhinovirus infection of PBEC leads to increased hBD-2 and hBD-3 mRNA expression, which may play a role in both the uncomplicated common cold and in virus-associated exacerbations of asthma. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.. antimicrobial peptide| defensin| epithelium| rhinovirus| respiratory infection|double-stranded-rna| human airway epithelia| nitric-oxide synthase| beta-defensins| dendritic cells| cystic-fibrosis| inhibition| interferon| gene| replication.	AUG 18-2003	antimicrobial peptide| defensin| epithelium| rhinovirus| respiratory infection|double-stranded-rna| human airway epithelia| nitric-oxide synthase| beta-defensins| dendritic cells| cystic-fibrosis| inhibition| interferon| gene| replication	Duits, LA; Nibbering, PH; van Strijen, E; Vos, JB; Mannesse-Lazeroms, SPG; van Sterkenburg, MAJA; Hiemstra, PS	Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells		FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY	antimicrobial peptide; defensin; epithelium; rhinovirus; respiratory infection	DOUBLE-STRANDED-RNA; HUMAN AIRWAY EPITHELIA; NITRIC-OXIDE SYNTHASE; BETA-DEFENSINS; DENDRITIC CELLS; CYSTIC-FIBROSIS; INHIBITION; INTERFERON; GENE; REPLICATION	Human beta-defensins (hBDs) are antimicrobial peptides that play important roles in host defense against infection, inflammation and immunity. Previous studies showed that micro-organisms and proinflammatory mediators regulate the expression of these peptides in airway epithelial cells. The aim of the present study was to investigate the modulation of expression of hBDs in cultured primary bronchial epithelial cells (PBEC) by rhinovirus-16 (RV16), a respiratory virus responsible for the common cold and associated with asthma exacerbations. RV16 was found to induce expression of hBD-2 and -3 mRNA in PBEC, but did not affect hBD-1 mRNA. Viral replication appeared essential for rhinovirus-induced beta-defensin mRNA expression, since UV-inactivated rhinovirus did not increase expression of hBD-2 and hBD-3 mRNA. Exposure to synthetic double-stranded RNA (dsRNA) molecule polyinosinic:polycytidylic acid had a similar effect as RV16 on mRNA expression of these peptides in PBEC. In line with this, PBEC were found to express TLR3, a Toll-like receptor involved in recognition of dsRNA. This study shows that rhinovirus infection of PBEC leads to increased hBD-2 and hBD-3 mRNA expression, which may play a role in both the uncomplicated common cold and in virus-associated exacerbations of asthma. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.	48	85	2003	6	10.1016/S0928-8244(03)00106-8	Immunology; Infectious Diseases; Microbiology
Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children. Background: Exhaled nitric oxide (eNO) may serve as a non-invasive marker of airway inflammation but its relationship with other commonly used measures has not been evaluated. Methods: Levels of eNO in a sample of 450 children aged 7-12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV1 and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. Results: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV, and MMEF were not associated with eNO levels. Conclusions: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health.. nasal nitric-oxide| asthmatic-patients| allergic rhinitis| air-pollution| mild asthma| responsiveness| inhibitor| synthase| season| sample.	MAR-2003	nasal nitric-oxide| asthmatic-patients| allergic rhinitis| air-pollution| mild asthma| responsiveness| inhibitor| synthase| season| sample	Steerenberg, PA; Janssen, NAH; de Meer, G; Fischer, PH; Nierkens, S; van Loveren, H; Opperhuizen, A; Brunekreef, B; van Amsterdam, JGC	Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children		THORAX		NASAL NITRIC-OXIDE; ASTHMATIC-PATIENTS; ALLERGIC RHINITIS; AIR-POLLUTION; MILD ASTHMA; RESPONSIVENESS; INHIBITOR; SYNTHASE; SEASON; SAMPLE	Background: Exhaled nitric oxide (eNO) may serve as a non-invasive marker of airway inflammation but its relationship with other commonly used measures has not been evaluated. Methods: Levels of eNO in a sample of 450 children aged 7-12 years out of a total sample of 2504 school children living in different urban areas near motorways were determined. The aim of this cross-sectional study was to explore the relationship between eNO, impairment of lung function (PEF, FVC, FEV1 and MMEF), bronchial hyperresponsiveness (BHR), and blood eosinophilia in children with and without atopy as assessed by skin prick testing. Results: Regression analysis showed that wheezing and nasal discharge and conjunctivitis that had occurred during the previous 12 months were positively associated with eNO levels in atopic children (relative increase of 1.48 and 1.41, respectively; p<0.05) but not in non-atopic children. Similarly, BHR and the number of blood eosinophils per ml were positively associated with eNO levels in atopic children (relative increase of 1.55 and 2.29, respectively; p<0.05) but not in non-atopic children. The lung function indices PEF, FVC, FEV, and MMEF were not associated with eNO levels. Conclusions: In addition to conventional lung function tests and symptom questionnaires, eNO is a suitable measure of airway inflammation and its application may reinforce the power of epidemiological surveys on respiratory health.	38	85	2003	4	10.1136/thorax.58.3.242	Respiratory System
Smoking patterns of household members and visitors in homes with children in the United States. Background: Environmental tobacco smoke (ETS), also called passive smoking, has been shown to have adverse effects on the health of children. Objective: To determine the prevalence and pattern of ETS exposure in US homes with children younger than 18 years. Design: We analyzed data from the 1994 National Health Interview Survey and Year 2000 Objectives supplement. A multistage sample design was used to represent the civilian, noninstitutionalized population of the United States. Main Outcome Measures: Frequency of smoking by household residents and visitors in homes with children. Results: Thirty-five percent of children in the United States-21 million children-live in homes where residents or visitors smoke in the home on a regular basis (greater than or equal to I d/wk). From the household perspective, regular smoking by residents and visitors occurs in 36% of homes in which children reside. in 92% of homes with children where residents smoke at home, they do so every day of the week. Sixteen percent of nonsmoking respondents with children report that other residents or visitors smoke in the home. In 6% of the homes where no residents smoke, there is nevertheless regular smoking by visitors. In multivariate regression analysis, the prevalence of regular smoking in homes with children varies by age of youngest child, race/ethnicity, number of parents in the home, parental educational level, income, and region of the country. Conclusions: Many children live in homes with ETS. Most respondents who smoke report that smoking occurs in the home every day. Visitors are an additional source of ETS in homes, including some homes where residents do not smoke. Clinicians who take care of children can advise parents, whether or not they smoke, on how to limit their children's ETS exposure.. environmental tobacco-smoke| nutrition examination survey| infant-death-syndrome| passive smoking| parental smoking| maternal smoking| cigarette-smoking| childhood asthma| urinary cotinine| national-health.	NOV-2002	environmental tobacco-smoke| nutrition examination survey| infant-death-syndrome| passive smoking| parental smoking| maternal smoking| cigarette-smoking| childhood asthma| urinary cotinine| national-health	Schuster, MA; Franke, T; Pham, CB	Smoking patterns of household members and visitors in homes with children in the United States		ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE		ENVIRONMENTAL TOBACCO-SMOKE; NUTRITION EXAMINATION SURVEY; INFANT-DEATH-SYNDROME; PASSIVE SMOKING; PARENTAL SMOKING; MATERNAL SMOKING; CIGARETTE-SMOKING; CHILDHOOD ASTHMA; URINARY COTININE; NATIONAL-HEALTH	Background: Environmental tobacco smoke (ETS), also called passive smoking, has been shown to have adverse effects on the health of children. Objective: To determine the prevalence and pattern of ETS exposure in US homes with children younger than 18 years. Design: We analyzed data from the 1994 National Health Interview Survey and Year 2000 Objectives supplement. A multistage sample design was used to represent the civilian, noninstitutionalized population of the United States. Main Outcome Measures: Frequency of smoking by household residents and visitors in homes with children. Results: Thirty-five percent of children in the United States-21 million children-live in homes where residents or visitors smoke in the home on a regular basis (greater than or equal to I d/wk). From the household perspective, regular smoking by residents and visitors occurs in 36% of homes in which children reside. in 92% of homes with children where residents smoke at home, they do so every day of the week. Sixteen percent of nonsmoking respondents with children report that other residents or visitors smoke in the home. In 6% of the homes where no residents smoke, there is nevertheless regular smoking by visitors. In multivariate regression analysis, the prevalence of regular smoking in homes with children varies by age of youngest child, race/ethnicity, number of parents in the home, parental educational level, income, and region of the country. Conclusions: Many children live in homes with ETS. Most respondents who smoke report that smoking occurs in the home every day. Visitors are an additional source of ETS in homes, including some homes where residents do not smoke. Clinicians who take care of children can advise parents, whether or not they smoke, on how to limit their children's ETS exposure.	70	85	2002	7		Pediatrics
Atopic dermatitis and fungi. Atopic dermatitis (AD) is a chronic, itching, inflammatory skin disease which is associated with asthma and/or hay fever and a familial occurrence of these conditions. Genetic factors are important in the development of AD, but the exact hereditary pathway is still unknown. Dry skin and the weakened barrier function in patients with AD is very important for the patient's reactions to irritants and other external trigger factors including microorganisms. The standard treatments are topical corticosteroids, topical immunomodulating agents, and emollients. If AD cannot be controlled by this type of treatment, systemic immunomodulating agents may be used. UVB, UVA, or psoralen-UVA may also be used for widespread severe lesions. However, some patients do not respond to these standard treatment, and then it is important to consider the role of microorganisms, house dust mites or food. The role of the Malassezia yeasts in AD, especially AD located to the head and neck region, is now documented in several papers. There are also several papers indicating the role of Candida as an aggravating factor in AD. Patients with AD also develop chronic dermatophyte infections more easily, and patients with AD and chronic dermatophyte infections may show improvement in their AD when treated with antifungal drugs.. ige-mediated hypersensitivity| yeast malassezia-furfur| candida-albicans mannan| cross-reacting ige| pityrosporum-ovale| staphylococcus-aureus| seborrheic dermatitis| pityriasis-versicolor| human-skin| therapeutic implications.	OCT-2002	ige-mediated hypersensitivity| yeast malassezia-furfur| candida-albicans mannan| cross-reacting ige| pityrosporum-ovale| staphylococcus-aureus| seborrheic dermatitis| pityriasis-versicolor| human-skin| therapeutic implications	Faergemann, J	Atopic dermatitis and fungi		CLINICAL MICROBIOLOGY REVIEWS		IGE-MEDIATED HYPERSENSITIVITY; YEAST MALASSEZIA-FURFUR; CANDIDA-ALBICANS MANNAN; CROSS-REACTING IGE; PITYROSPORUM-OVALE; STAPHYLOCOCCUS-AUREUS; SEBORRHEIC DERMATITIS; PITYRIASIS-VERSICOLOR; HUMAN-SKIN; THERAPEUTIC IMPLICATIONS	Atopic dermatitis (AD) is a chronic, itching, inflammatory skin disease which is associated with asthma and/or hay fever and a familial occurrence of these conditions. Genetic factors are important in the development of AD, but the exact hereditary pathway is still unknown. Dry skin and the weakened barrier function in patients with AD is very important for the patient's reactions to irritants and other external trigger factors including microorganisms. The standard treatments are topical corticosteroids, topical immunomodulating agents, and emollients. If AD cannot be controlled by this type of treatment, systemic immunomodulating agents may be used. UVB, UVA, or psoralen-UVA may also be used for widespread severe lesions. However, some patients do not respond to these standard treatment, and then it is important to consider the role of microorganisms, house dust mites or food. The role of the Malassezia yeasts in AD, especially AD located to the head and neck region, is now documented in several papers. There are also several papers indicating the role of Candida as an aggravating factor in AD. Patients with AD also develop chronic dermatophyte infections more easily, and patients with AD and chronic dermatophyte infections may show improvement in their AD when treated with antifungal drugs.	169	85	2002	20	10.1128/CMR.15.4.545-563.2002	Microbiology
Expression and function of the ST2 gene in a murine model of allergic airway inflammation. Background We have recently reported that soluble ST2 protein levels are elevated in the sera of patients with asthma, and correlate well with the severity of asthma exacerbation. However, the role, function, and kinetics of soluble ST2 expression in asthma remain unclear. Objective The objective of the present study was to clarify the function and kinetics of soluble murine (m) ST2 expression in a murine asthma model. Methods We analyzed the kinetics of gene and protein expression of mST2 in sera or lung tissue after allergen (ovalbumin; OVA) challenge in a murine model of allergic airway inflammation, the effects of mST2 protein on OVA-induced Th2 cytokine production in vitro from splenocytes of sensitized mice, and the effects of soluble mST2 on Th2-dependent allergic airway inflammation by in vivo gene transfer of mST2. Results Serum mST2 protein levels increased to the maximal level 3 h after the allergen challenge, before serum IL-5 levels peaked. The mRNA expression of mST2 in lung tissue was induced after the allergen challenge, while that in the spleen was constitutively detected. Furthermore, pre-treatment with mST2 protein significantly inhibited the production of IL-4 and IL-5, but not IFN-gamma, from OVA-stimulated splenocytes in vitro, and intravenous mST2 gene transfer resulted in a drastic reduction in the number of eosinophils and in the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid, compared with those in response to transfer of non-coding plasmid vector or of lipid alone. Conclusion These results suggest that increases in endogenous mST2 protein after allergen exposure may modulate Th2-mediated airway inflammation, and that in vivo gene transfer of mST2 can be applicable to use in a novel immunotherapy for allergic diseases.. asthma| allergy| gene therapy| type-2 helper t cell| t1/st2|helper t-cells| interleukin-1 receptor| effector function| responsive gene| promoter usage| il-1 receptor| mast-cells| asthma| protein| t1/st2.	OCT-2002	asthma| allergy| gene therapy| type-2 helper t cell| t1/st2|helper t-cells| interleukin-1 receptor| effector function| responsive gene| promoter usage| il-1 receptor| mast-cells| asthma| protein| t1/st2	Oshikawa, K; Yanagisawa, K; Tominaga, S; Sugiyama, Y	Expression and function of the ST2 gene in a murine model of allergic airway inflammation		CLINICAL AND EXPERIMENTAL ALLERGY	asthma; allergy; gene therapy; type-2 helper T cell; T1/ST2	HELPER T-CELLS; INTERLEUKIN-1 RECEPTOR; EFFECTOR FUNCTION; RESPONSIVE GENE; PROMOTER USAGE; IL-1 RECEPTOR; MAST-CELLS; ASTHMA; PROTEIN; T1/ST2	Background We have recently reported that soluble ST2 protein levels are elevated in the sera of patients with asthma, and correlate well with the severity of asthma exacerbation. However, the role, function, and kinetics of soluble ST2 expression in asthma remain unclear. Objective The objective of the present study was to clarify the function and kinetics of soluble murine (m) ST2 expression in a murine asthma model. Methods We analyzed the kinetics of gene and protein expression of mST2 in sera or lung tissue after allergen (ovalbumin; OVA) challenge in a murine model of allergic airway inflammation, the effects of mST2 protein on OVA-induced Th2 cytokine production in vitro from splenocytes of sensitized mice, and the effects of soluble mST2 on Th2-dependent allergic airway inflammation by in vivo gene transfer of mST2. Results Serum mST2 protein levels increased to the maximal level 3 h after the allergen challenge, before serum IL-5 levels peaked. The mRNA expression of mST2 in lung tissue was induced after the allergen challenge, while that in the spleen was constitutively detected. Furthermore, pre-treatment with mST2 protein significantly inhibited the production of IL-4 and IL-5, but not IFN-gamma, from OVA-stimulated splenocytes in vitro, and intravenous mST2 gene transfer resulted in a drastic reduction in the number of eosinophils and in the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid, compared with those in response to transfer of non-coding plasmid vector or of lipid alone. Conclusion These results suggest that increases in endogenous mST2 protein after allergen exposure may modulate Th2-mediated airway inflammation, and that in vivo gene transfer of mST2 can be applicable to use in a novel immunotherapy for allergic diseases.	33	85	2002	7	10.1046/j.1365-2745.2002.01494.x	Allergy; Immunology
Eosinophilic bronchitis: clinical manifestations and implications for treatment. Airway inflammation with eosinophils is now reported to occur not only in asthma but in other airway diseases such as cough variant asthma, chronic cough, atopic cough, episodic symptoms without asthma, allergic rhinitis, and COPD. Although the prevalence of eosinophilic bronchitis (EB) is less than in asthma, the causes, mechanisms and treatment of EB in these conditions appears to be similar to asthma where allergen induced IL-5 secretion and symptoms are readily responsive to inhaled corticosteroids. The prognosis of EB without asthma is not known but it may be a precursor for asthma and, if so, recognition of this syndrome may permit effective treatment and reduction in the rising prevalence of asthma. Induced sputum analysis allows recognition of EB in clinical practice. The place of the asthma treatment paradigm with early and sustained corticosteroid treatment needs to be defined in EB without asthma. Airway wall remodelling can occur in rhinitis, COPD, and cough variant asthma with EB. The mechanisms and long term implications of this complication in EB without asthma need to be clarified.. obstructive pulmonary-disease| cough-variant asthma| chronic nonproductive cough| air-flow obstruction| sputum eosinophilia| allergic rhinitis| inflammation| hyperresponsiveness| responsiveness| children.	FEB-2002	obstructive pulmonary-disease| cough-variant asthma| chronic nonproductive cough| air-flow obstruction| sputum eosinophilia| allergic rhinitis| inflammation| hyperresponsiveness| responsiveness| children	Gibson, PG; Fujimura, M; Niimi, A	Eosinophilic bronchitis: clinical manifestations and implications for treatment		THORAX		OBSTRUCTIVE PULMONARY-DISEASE; COUGH-VARIANT ASTHMA; CHRONIC NONPRODUCTIVE COUGH; AIR-FLOW OBSTRUCTION; SPUTUM EOSINOPHILIA; ALLERGIC RHINITIS; INFLAMMATION; HYPERRESPONSIVENESS; RESPONSIVENESS; CHILDREN	Airway inflammation with eosinophils is now reported to occur not only in asthma but in other airway diseases such as cough variant asthma, chronic cough, atopic cough, episodic symptoms without asthma, allergic rhinitis, and COPD. Although the prevalence of eosinophilic bronchitis (EB) is less than in asthma, the causes, mechanisms and treatment of EB in these conditions appears to be similar to asthma where allergen induced IL-5 secretion and symptoms are readily responsive to inhaled corticosteroids. The prognosis of EB without asthma is not known but it may be a precursor for asthma and, if so, recognition of this syndrome may permit effective treatment and reduction in the rising prevalence of asthma. Induced sputum analysis allows recognition of EB in clinical practice. The place of the asthma treatment paradigm with early and sustained corticosteroid treatment needs to be defined in EB without asthma. Airway wall remodelling can occur in rhinitis, COPD, and cough variant asthma with EB. The mechanisms and long term implications of this complication in EB without asthma need to be clarified.	82	85	2002	5	10.1136/thorax.57.2.178	Respiratory System
The National Asthma Campaign Manchester Asthma and Allergy Study. The (NAC)Manchester Asthma and Allergy Study is a prospective study of the development of asthma and allergies in childhood. The subjects (995 children at age 3 years) were recruited in utero by screening parents in the antenatal clinic using skin prick testing and a questionnaire regarding allergic diseases. Children were assigned to risk groups according to parental atopic status (high risk, both parents atopic; medium risk, one parent atopic; low risk, neither parent atopic). A subgroup of those at high risk (with no pets in the home) was randomized to stringent environmental control (allergen impermeable covers for the parental and infant bed, hot washing of bedding weekly, HEPA vacuum cleaner, hard floor for the nursery), and the remainder followed a normal regime. The children have been followed prospectively. The environmental influences are very clearly defined. Measurements of environmental exposures include levels of house dust mite; cat and dog allergens during pregnancy and early life; pet ownership and exposure; childcare arrangements; number of siblings; vaccination uptake; thorough dietary questionnaire and endotoxin exposure. Further unique objective outcome in the cohort is the assessment of lung function in preschool children using specific airways resistance, which at age 3 years clearly reflects both genetic and environmental influences.. allergens| asthma| atopy| prevention| sensitization|young-children| early-life| pregnancy.	2002	allergens| asthma| atopy| prevention| sensitization|young-children| early-life| pregnancy	Custovic, A; Simpson, BM; Murray, CS; Lowe, L; Woodcock, A	The National Asthma Campaign Manchester Asthma and Allergy Study		PEDIATRIC ALLERGY AND IMMUNOLOGY	allergens; asthma; atopy; prevention; sensitization	YOUNG-CHILDREN; EARLY-LIFE; PREGNANCY	The (NAC)Manchester Asthma and Allergy Study is a prospective study of the development of asthma and allergies in childhood. The subjects (995 children at age 3 years) were recruited in utero by screening parents in the antenatal clinic using skin prick testing and a questionnaire regarding allergic diseases. Children were assigned to risk groups according to parental atopic status (high risk, both parents atopic; medium risk, one parent atopic; low risk, neither parent atopic). A subgroup of those at high risk (with no pets in the home) was randomized to stringent environmental control (allergen impermeable covers for the parental and infant bed, hot washing of bedding weekly, HEPA vacuum cleaner, hard floor for the nursery), and the remainder followed a normal regime. The children have been followed prospectively. The environmental influences are very clearly defined. Measurements of environmental exposures include levels of house dust mite; cat and dog allergens during pregnancy and early life; pet ownership and exposure; childcare arrangements; number of siblings; vaccination uptake; thorough dietary questionnaire and endotoxin exposure. Further unique objective outcome in the cohort is the assessment of lung function in preschool children using specific airways resistance, which at age 3 years clearly reflects both genetic and environmental influences.	8	85	2002	6	10.1034/j.1399-3038.13.s.15.3.x	Allergy; Immunology; Pediatrics
Risk factor associations with wheezing patterns in children followed longitudinally from birth to 3 1/2 years. Background There is a paucity of detailed longitudinal data on wheeze in early childhood. Not. all children who wheeze in early infancy will continue to wheeze into childhood and beyond. This study aims to investigate possible risk factors for different patterns of wheeze in the pre-school years. Subjects and Study participants. were part of.the.Avon Longitudinal Study of.Parents.and Methods Children (ALSPAC). Maternal reports of child wheeze between birth and 6 months and again between 30 and 42 months were gathered prospectively. Children were categorized into early wheeze, persistent wheeze or late onset wheeze. A large number of risk factors were assessed for each wheezing phenotype using multivariable logistic regression models. Results Over 70% of children who wheezed in the first 6 months did not wheeze 3 years later. Wheezing between 0-6 months was independently associated with the presence of older siblings, male sex, delivery between April and December, bottle feeding, young maternal age, prenatal tobacco smoke exposure, atopy and parental history of asthma. From within this group of early wheezers, risk factors for wheeze that persisted beyond 6 months included pre-term delivery; young maternal age, living in rented local authority housing, atopy and a maternal (not paternal) history of asthma. Atopy and a family history of asthma emerged as the main predictors of wheeze that developed after 6 months of age. Conclusion It is clear that a number of wheezing syndromes exist by 3 1/2 years, albeit with some degree of overlap. Detailed follow-up of this cohort is underway to determine whether risk factor associations determined in the first 3 1/2 years have long-term significance for the clinical entity termed 'asthma'.. alspac| infant wheeze| risk factors|lower respiratory-tract| day-care attendance| maternal smoking| parental smoking| asthma| atopy| life| infections| persistent| illnesses.	DEC-2001	alspac| infant wheeze| risk factors|lower respiratory-tract| day-care attendance| maternal smoking| parental smoking| asthma| atopy| life| infections| persistent| illnesses	Sherriff, A; Peters, TJ; Henderson, J; Strachan, D	Risk factor associations with wheezing patterns in children followed longitudinally from birth to 3 1/2 years		INTERNATIONAL JOURNAL OF EPIDEMIOLOGY	ALSPAC; infant wheeze; risk factors	LOWER RESPIRATORY-TRACT; DAY-CARE ATTENDANCE; MATERNAL SMOKING; PARENTAL SMOKING; ASTHMA; ATOPY; LIFE; INFECTIONS; PERSISTENT; ILLNESSES	Background There is a paucity of detailed longitudinal data on wheeze in early childhood. Not. all children who wheeze in early infancy will continue to wheeze into childhood and beyond. This study aims to investigate possible risk factors for different patterns of wheeze in the pre-school years. Subjects and Study participants. were part of.the.Avon Longitudinal Study of.Parents.and Methods Children (ALSPAC). Maternal reports of child wheeze between birth and 6 months and again between 30 and 42 months were gathered prospectively. Children were categorized into early wheeze, persistent wheeze or late onset wheeze. A large number of risk factors were assessed for each wheezing phenotype using multivariable logistic regression models. Results Over 70% of children who wheezed in the first 6 months did not wheeze 3 years later. Wheezing between 0-6 months was independently associated with the presence of older siblings, male sex, delivery between April and December, bottle feeding, young maternal age, prenatal tobacco smoke exposure, atopy and parental history of asthma. From within this group of early wheezers, risk factors for wheeze that persisted beyond 6 months included pre-term delivery; young maternal age, living in rented local authority housing, atopy and a maternal (not paternal) history of asthma. Atopy and a family history of asthma emerged as the main predictors of wheeze that developed after 6 months of age. Conclusion It is clear that a number of wheezing syndromes exist by 3 1/2 years, albeit with some degree of overlap. Detailed follow-up of this cohort is underway to determine whether risk factor associations determined in the first 3 1/2 years have long-term significance for the clinical entity termed 'asthma'.	24	85	2001	12	10.1093/ije/30.6.1473	Public, Environmental & Occupational Health
Local increase in the number of mast cells and expression of nerve growth factor in the bronchus of asthmatic patients after repeated inhalation of allergen at low-dose. Background Repeated inhalation of allergen at low-dose induces an increase in bronchial hyper-responsiveness, without any associated symptom. The concomitant events in the bronchus have not been described. Objective We have studied the dynamic number of mast cells in the airways of patients with mild asthma before and after repeated inhalation of allergen at low-dose and the expression of nerve growth factor (NGF), which is reported to promote growth and survival of mast cells. Methods Twelve patients with mild asthma to cat allergen were enrolled at random in a blind placebo-controlled study, and submitted to repeated low-dose allergen exposure (1/5 of the provocative dose). Mast cells were immunolocalized using an antibody against mast cell tryptase. NGF and its high affinity receptor, TrkA, were immunolocalized using anti-NGF and anti-TrkA antibodies, respectively. NGF mRNA was quantified by competitive polymerase chain reaction (PCR) after reverse transcription of total RNA extracted from bronchial biopsy. NGF protein levels were measured by ELISA in bronchoalveolar lavage (BAL) fluid. Results Bronchial mast cell number was increased significantly after allergen exposure as compared with before. NGF expression in the bronchus was immunolocalized mainly to epithelial cells, but also to fibroblasts, blood vessels, and a few infiltrated cells. NGF mRNA levels in bronchial biopsies were increased significantly after allergen exposure. The high affinity receptor for NGF, TrkA, was immunolocalized to the infiltrated mast cell membrane. Conclusion Our study shows that the increase in the number of mast cells and in the expression of NGF induced by allergen exposure in the bronchus of asthmatic patients is occurring before the onset of symptoms. In addition, our finding of the presence of the TrkA receptor on the membrane of the infiltrated mast cell in situ brings evidence of the mast cell as a target cell for the growth factor activity of NGF in the airways in asthma.. neurotrophin| asthma| airway| mast cell| ngf| tryptase| allergy| bronchus| bronchoalveolar lavage| bronchial biopsy|airway mucosal inflammation| survival promotion| peripheral-blood| functional trka| up-regulation| mild asthma| progenitors| exposure| receptor| model.	SEP-2001	neurotrophin| asthma| airway| mast cell| ngf| tryptase| allergy| bronchus| bronchoalveolar lavage| bronchial biopsy|airway mucosal inflammation| survival promotion| peripheral-blood| functional trka| up-regulation| mild asthma| progenitors| exposure| receptor| model	Kassel, O; De Blay, F; Duvernelle, C; Olgart, C; Israel-Biet, D; Krieger, P; Moreau, L; Muller, C; Pauli, G; Frossard, N	Local increase in the number of mast cells and expression of nerve growth factor in the bronchus of asthmatic patients after repeated inhalation of allergen at low-dose		CLINICAL AND EXPERIMENTAL ALLERGY	neurotrophin; asthma; airway; mast cell; NGF; tryptase; allergy; bronchus; bronchoalveolar lavage; bronchial biopsy	AIRWAY MUCOSAL INFLAMMATION; SURVIVAL PROMOTION; PERIPHERAL-BLOOD; FUNCTIONAL TRKA; UP-REGULATION; MILD ASTHMA; PROGENITORS; EXPOSURE; RECEPTOR; MODEL	Background Repeated inhalation of allergen at low-dose induces an increase in bronchial hyper-responsiveness, without any associated symptom. The concomitant events in the bronchus have not been described. Objective We have studied the dynamic number of mast cells in the airways of patients with mild asthma before and after repeated inhalation of allergen at low-dose and the expression of nerve growth factor (NGF), which is reported to promote growth and survival of mast cells. Methods Twelve patients with mild asthma to cat allergen were enrolled at random in a blind placebo-controlled study, and submitted to repeated low-dose allergen exposure (1/5 of the provocative dose). Mast cells were immunolocalized using an antibody against mast cell tryptase. NGF and its high affinity receptor, TrkA, were immunolocalized using anti-NGF and anti-TrkA antibodies, respectively. NGF mRNA was quantified by competitive polymerase chain reaction (PCR) after reverse transcription of total RNA extracted from bronchial biopsy. NGF protein levels were measured by ELISA in bronchoalveolar lavage (BAL) fluid. Results Bronchial mast cell number was increased significantly after allergen exposure as compared with before. NGF expression in the bronchus was immunolocalized mainly to epithelial cells, but also to fibroblasts, blood vessels, and a few infiltrated cells. NGF mRNA levels in bronchial biopsies were increased significantly after allergen exposure. The high affinity receptor for NGF, TrkA, was immunolocalized to the infiltrated mast cell membrane. Conclusion Our study shows that the increase in the number of mast cells and in the expression of NGF induced by allergen exposure in the bronchus of asthmatic patients is occurring before the onset of symptoms. In addition, our finding of the presence of the TrkA receptor on the membrane of the infiltrated mast cell in situ brings evidence of the mast cell as a target cell for the growth factor activity of NGF in the airways in asthma.	47	85	2001	9	10.1046/j.1365-2222.2001.01177.x	Allergy; Immunology
Chicken serum albumin (Gal d 5*) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome. Background: Chicken serum albumin (alpha -livetin) has been implicated as the causative allergen of the bird-egg syndrome. However, the clinical relevance of sensitization to this allergen has not been confirmed by specific challenge tests and environmental sampling. We investigated whether chicken albumin can be detected in air samples collected in a home with birds, and whether sensitization to this protein may cause respiratory and food allergy symptoms. The heat resistance of chicken albumin and the possible cross-reactivity with conalbumin were also investigated. Methods: We studied eight patients with food allergy to egg yolk who also suffered from respiratory symptoms (rhinitis and/or asthma) caused by exposure to birds. Sensitization to egg yolk and bird antigens was investigated by skin and serologic tests. Hypersensitivity to chicken albumin was confirmed by specific bronchial, conjunctival, and oral provocation tests. Results. All patients had positive skin tests and serum IgE against egg yolk, chicken serum, chicken meat, bird feathers, and chicken albumin. The presence of airborne chicken albumin in the domestic environment was confirmed. Specific bronchial challenge to chicken albumin elicited early asthmatic responses in six patients with asthma. An oral challenge with chicken albumin provoked digestive and systemic allergic symptoms in the two patients challenged. IgE reactivity to chicken albumin was reduced by 88% after heating at 90 degreesC for 30 min. ELISA inhibition demonstrated only partial cross-reactivity between chicken albumin and conalbumin. Conclusions: Chicken albumin (Gal d 5) is a partially heat-labile allergen that may cause both respiratory and food-allergy symptoms in patients with the bird-egg syndrome.. allergic asthma| bird-egg syndrome| chicken albumin| egg allergy| feathers|occupational asthma| cross-reactivity| alpha-livetin| proteins| yolk| identification| disease| white| beef.	AUG-2001	allergic asthma| bird-egg syndrome| chicken albumin| egg allergy| feathers|occupational asthma| cross-reactivity| alpha-livetin| proteins| yolk| identification| disease| white| beef	Quirce, S; Maranon, F; Umpierrez, A; de las Heras, M; Fernandez-Caldas, E; Sastre, J	Chicken serum albumin (Gal d 5*) is a partially heat-labile inhalant and food allergen implicated in the bird-egg syndrome		ALLERGY	allergic asthma; bird-egg syndrome; chicken albumin; egg allergy; feathers	OCCUPATIONAL ASTHMA; CROSS-REACTIVITY; ALPHA-LIVETIN; PROTEINS; YOLK; IDENTIFICATION; DISEASE; WHITE; BEEF	Background: Chicken serum albumin (alpha -livetin) has been implicated as the causative allergen of the bird-egg syndrome. However, the clinical relevance of sensitization to this allergen has not been confirmed by specific challenge tests and environmental sampling. We investigated whether chicken albumin can be detected in air samples collected in a home with birds, and whether sensitization to this protein may cause respiratory and food allergy symptoms. The heat resistance of chicken albumin and the possible cross-reactivity with conalbumin were also investigated. Methods: We studied eight patients with food allergy to egg yolk who also suffered from respiratory symptoms (rhinitis and/or asthma) caused by exposure to birds. Sensitization to egg yolk and bird antigens was investigated by skin and serologic tests. Hypersensitivity to chicken albumin was confirmed by specific bronchial, conjunctival, and oral provocation tests. Results. All patients had positive skin tests and serum IgE against egg yolk, chicken serum, chicken meat, bird feathers, and chicken albumin. The presence of airborne chicken albumin in the domestic environment was confirmed. Specific bronchial challenge to chicken albumin elicited early asthmatic responses in six patients with asthma. An oral challenge with chicken albumin provoked digestive and systemic allergic symptoms in the two patients challenged. IgE reactivity to chicken albumin was reduced by 88% after heating at 90 degreesC for 30 min. ELISA inhibition demonstrated only partial cross-reactivity between chicken albumin and conalbumin. Conclusions: Chicken albumin (Gal d 5) is a partially heat-labile allergen that may cause both respiratory and food-allergy symptoms in patients with the bird-egg syndrome.	43	85	2001	9	10.1034/j.1398-9995.2001.056008754.x	Allergy; Immunology
Increased prevalence of asthma in saudi Arabia. Background: Branchial asthma is among the most common chronic illnesses of childhood. A number of reports in the recent past suggest that the prevalence of asthma is increasing globally. Objective: To investigate the changing prevalence of asthma in the Kingdom of Saudi Arabia. Subjects and Methods: Two populations of schoolchildren between the ages of 8 and 16 years were studied using an internationally designed protocol in 1986 and 1995. The questionnaire used in these studies was very similar to the one used in the International Study of Allergy and Asthma in Childhood. A total of 2,123 schoolchildren in 1986 (Jeddah and Riyadh) and 1,008 schoolchildren in 1995 (Hail and Gizan) were enrolled in the surveys. These cross-sectional studies of randomly selected schoolchildren were statistically analyzed using ANOVA and a Z test. Results: The comparison of data between Riyadh versus Hail (inland desert dry environment) and Jeddah versus Gizan (coastal humid environment) revealed that the prevalence of asthma in the similar populations increased significantly from 8% in 1986 to 23% in 1995 (P < .0001). Likewise, the prevalence of allergic rhinitis also increased from 20% to 25% (P < .003) since 1986. However, no significant change in the prevalence of eczema (from 12% to 13%) was noted between 1986 and 1995. Conclusions: The study indicates that there was a significant increase in the prevalence of bronchial asthma and, to a lesser extent, in the prevalence of allergic rhinitis in the Kingdom of Saudi Arabia during this 9-year period. The study also revealed increased exposure to environmental factors such as tobacco smoke and indoor animals in Saudi houses. It seems that the continuing changes in contemporary life may well have contributed to the increased prevalence of asthma in the country.. swedish school-children| skin-test reactivity| respiratory symptoms| changing prevalence| allergic diseases| bronchial-asthma| schoolchildren| atopy| epidemiology| adolescents.	MAR-2001	swedish school-children| skin-test reactivity| respiratory symptoms| changing prevalence| allergic diseases| bronchial-asthma| schoolchildren| atopy| epidemiology| adolescents	Al Frayh, AR; Shakoor, Z; El Rab, MOG; Hasnain, SM	Increased prevalence of asthma in saudi Arabia		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		SWEDISH SCHOOL-CHILDREN; SKIN-TEST REACTIVITY; RESPIRATORY SYMPTOMS; CHANGING PREVALENCE; ALLERGIC DISEASES; BRONCHIAL-ASTHMA; SCHOOLCHILDREN; ATOPY; EPIDEMIOLOGY; ADOLESCENTS	Background: Branchial asthma is among the most common chronic illnesses of childhood. A number of reports in the recent past suggest that the prevalence of asthma is increasing globally. Objective: To investigate the changing prevalence of asthma in the Kingdom of Saudi Arabia. Subjects and Methods: Two populations of schoolchildren between the ages of 8 and 16 years were studied using an internationally designed protocol in 1986 and 1995. The questionnaire used in these studies was very similar to the one used in the International Study of Allergy and Asthma in Childhood. A total of 2,123 schoolchildren in 1986 (Jeddah and Riyadh) and 1,008 schoolchildren in 1995 (Hail and Gizan) were enrolled in the surveys. These cross-sectional studies of randomly selected schoolchildren were statistically analyzed using ANOVA and a Z test. Results: The comparison of data between Riyadh versus Hail (inland desert dry environment) and Jeddah versus Gizan (coastal humid environment) revealed that the prevalence of asthma in the similar populations increased significantly from 8% in 1986 to 23% in 1995 (P < .0001). Likewise, the prevalence of allergic rhinitis also increased from 20% to 25% (P < .003) since 1986. However, no significant change in the prevalence of eczema (from 12% to 13%) was noted between 1986 and 1995. Conclusions: The study indicates that there was a significant increase in the prevalence of bronchial asthma and, to a lesser extent, in the prevalence of allergic rhinitis in the Kingdom of Saudi Arabia during this 9-year period. The study also revealed increased exposure to environmental factors such as tobacco smoke and indoor animals in Saudi houses. It seems that the continuing changes in contemporary life may well have contributed to the increased prevalence of asthma in the country.	40	85	2001	5		Allergy; Immunology
Expression of heme oxygenase isoenzymes 1 and 2 in normal and asthmatic airways - Effect of inhaled corticosteroids. Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. We determined the expression and distribution of HO-1 and HO-2, two isoenzymes of HO, in the airways of patients with asthma, and determined the effect of inhaled corticosteroid therapy. Immunostaining for both enzymes was widely distributed in the airways' submucosa, particularly in airway epithelium and submucosal macrophages (CD68(+)) as determined by double immunostaining. There was no difference in intensity and extent of staining in biopsies from normal subjects (n = 10) and subjects with asthma (n = 10). Following 1 mo of treatment with inhaled corticosteroids (budesonide 1,600 mug/d), there was no significant change in the expression and distribution of either HO-1 or HO-2 in the airways' submucosa in eight subjects with mild asthma, despite a significant reduction in airway eosinophils and a reduction in bronchial responsiveness to methacholine. Levels of exhaled nitric oxide were significantly reduced, but exhaled CO levels remained unchanged by the treatment. Treatment with a placebo inhaler (n = 8) had no effects on these parameters. Thus, both HO-1 and HO-2 are extensively distributed equally in normal subjects and subjects with asthma, and are not modulated by inhaled corticosteroid therapy in subjects with asthma. HO may be an important endogenous antioxidant enzyme.. particulate air-pollution| human-skin fibroblasts| nitric-oxide synthase| hydrogen-peroxide| oxidative stress| messenger-rna| epithelial-cells| gene-expression| carbon-monoxide| in-vitro.	NOV-2000	particulate air-pollution| human-skin fibroblasts| nitric-oxide synthase| hydrogen-peroxide| oxidative stress| messenger-rna| epithelial-cells| gene-expression| carbon-monoxide| in-vitro	Lim, S; Groneberg, D; Fischer, A; Oates, T; Caramori, G; Mattos, W; Adcock, I; Barnes, PJ; Chung, KF	Expression of heme oxygenase isoenzymes 1 and 2 in normal and asthmatic airways - Effect of inhaled corticosteroids		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE		PARTICULATE AIR-POLLUTION; HUMAN-SKIN FIBROBLASTS; NITRIC-OXIDE SYNTHASE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; MESSENGER-RNA; EPITHELIAL-CELLS; GENE-EXPRESSION; CARBON-MONOXIDE; IN-VITRO	Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. We determined the expression and distribution of HO-1 and HO-2, two isoenzymes of HO, in the airways of patients with asthma, and determined the effect of inhaled corticosteroid therapy. Immunostaining for both enzymes was widely distributed in the airways' submucosa, particularly in airway epithelium and submucosal macrophages (CD68(+)) as determined by double immunostaining. There was no difference in intensity and extent of staining in biopsies from normal subjects (n = 10) and subjects with asthma (n = 10). Following 1 mo of treatment with inhaled corticosteroids (budesonide 1,600 mug/d), there was no significant change in the expression and distribution of either HO-1 or HO-2 in the airways' submucosa in eight subjects with mild asthma, despite a significant reduction in airway eosinophils and a reduction in bronchial responsiveness to methacholine. Levels of exhaled nitric oxide were significantly reduced, but exhaled CO levels remained unchanged by the treatment. Treatment with a placebo inhaler (n = 8) had no effects on these parameters. Thus, both HO-1 and HO-2 are extensively distributed equally in normal subjects and subjects with asthma, and are not modulated by inhaled corticosteroid therapy in subjects with asthma. HO may be an important endogenous antioxidant enzyme.	36	85	2000	7		General & Internal Medicine; Respiratory System
Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing. Background: Eosinophilic airway inflammation is the hallmark of asthma, but it has also been reported in other conditions such as allergic rhinitis. We have tested whether the analysis of cells and chemicals in sputum can distinguish between patients with mild allergic asthma, those with allergic rhinitis, and healthy controls. The relationship between inflammation markers in sputum and nonspecific bronchial hyperresponsiveness to methacholine (BHR) (PD20 and maximal response plateau [MRP] values) was also evaluated. Methods: We selected 31 mild asthmatics and 15 rhinitis patients sensitized to house-dust mite. As a control group, we studied 10 healthy subjects. Every subject underwent the methacholine bronchial provocation test (M-BPT) and sputum induction. Blood eosinophils and serum ECP levels were measured. Sputum cell differentials were assessed, and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin (IL)-5 levels were measured in the entire sputum supernatant. Results: Blood eosinophils and serum ECP levels were higher in asthma patients and rhinitis than in healthy controls, but no difference: between asthma patients and rhinitis patients was found. Asthmatics had higher eosinophil counts and higher ECP and tryptase levels in sputum than rhinitis patients or control subjects. Sputum albumin levels were higher in asthmatics than in controls. Rhinitis patients exhibited higher sputum eosinophils than healthy controls. An association between sputum eosinophil numbers and MPR values (r = -0.57) was detected, and a trend toward correlation between sputum ECP levels and PD20 values (r = -0.47) was found in the rhinitis group, but not in asthmatics. No correlation between blood eosinophilic inflammation and lung functional indices was found. Conclusions: Induced sputum is an accurate method to study bronchial inflammation, allowing one to distinguish between rhinitis patients and mildly asthmatic patients. The fact that no relationship was detected between sputum inflammation and BHR suggests that other factors, such as airway remodeling, may be at least partly responsible for BHR in asthma.. airway inflammation| asthma| eosinophil cationic protein| eosinophils| induced sputum| maximal response plateau| nonspecific bronchial hyperresponsiveness| rhinitis| tryptase|induced sputum| mast-cells| bronchoalveolar lavage| healthy-subjects| eosinophils| blood| hyperresponsiveness| reproducibility| challenge| biopsies.	APR-2000	airway inflammation| asthma| eosinophil cationic protein| eosinophils| induced sputum| maximal response plateau| nonspecific bronchial hyperresponsiveness| rhinitis| tryptase|induced sputum| mast-cells| bronchoalveolar lavage| healthy-subjects| eosinophils| blood| hyperresponsiveness| reproducibility| challenge| biopsies	Alvarez, MJ; Olaguibel, JM; Garcia, BE; Rodriguez, A; Tabar, AI; Urbiola, E	Airway inflammation in asthma and perennial allergic rhinitis. Relationship with nonspecific bronchial responsiveness and maximal airway narrowing		ALLERGY	airway inflammation; asthma; eosinophil cationic protein; eosinophils; induced sputum; maximal response plateau; nonspecific bronchial hyperresponsiveness; rhinitis; tryptase	INDUCED SPUTUM; MAST-CELLS; BRONCHOALVEOLAR LAVAGE; HEALTHY-SUBJECTS; EOSINOPHILS; BLOOD; HYPERRESPONSIVENESS; REPRODUCIBILITY; CHALLENGE; BIOPSIES	Background: Eosinophilic airway inflammation is the hallmark of asthma, but it has also been reported in other conditions such as allergic rhinitis. We have tested whether the analysis of cells and chemicals in sputum can distinguish between patients with mild allergic asthma, those with allergic rhinitis, and healthy controls. The relationship between inflammation markers in sputum and nonspecific bronchial hyperresponsiveness to methacholine (BHR) (PD20 and maximal response plateau [MRP] values) was also evaluated. Methods: We selected 31 mild asthmatics and 15 rhinitis patients sensitized to house-dust mite. As a control group, we studied 10 healthy subjects. Every subject underwent the methacholine bronchial provocation test (M-BPT) and sputum induction. Blood eosinophils and serum ECP levels were measured. Sputum cell differentials were assessed, and eosinophil cationic protein (ECP), tryptase, albumin, and interleukin (IL)-5 levels were measured in the entire sputum supernatant. Results: Blood eosinophils and serum ECP levels were higher in asthma patients and rhinitis than in healthy controls, but no difference: between asthma patients and rhinitis patients was found. Asthmatics had higher eosinophil counts and higher ECP and tryptase levels in sputum than rhinitis patients or control subjects. Sputum albumin levels were higher in asthmatics than in controls. Rhinitis patients exhibited higher sputum eosinophils than healthy controls. An association between sputum eosinophil numbers and MPR values (r = -0.57) was detected, and a trend toward correlation between sputum ECP levels and PD20 values (r = -0.47) was found in the rhinitis group, but not in asthmatics. No correlation between blood eosinophilic inflammation and lung functional indices was found. Conclusions: Induced sputum is an accurate method to study bronchial inflammation, allowing one to distinguish between rhinitis patients and mildly asthmatic patients. The fact that no relationship was detected between sputum inflammation and BHR suggests that other factors, such as airway remodeling, may be at least partly responsible for BHR in asthma.	33	85	2000	8	10.1034/j.1398-9995.2000.00312.x	Allergy; Immunology
Polymorphisms at the glutathione S-transferase, GSTP1 locus: a novel mechanism for susceptibility and development of atopic airway inflammation. A common feature of environmental irritants is their ability to cause local inflammation which could alter airway function. The principal targets of such injury are the epithelial cells lining the airway passages and the lower respiratory gas-exchange areas. While host atopy is a recognized risk factor for airway inflammation, atopy alone cannot cause asthma. We hypothesize that susceptibility to persistent airway inflammation in atopic individuals is characterized by an inherited deficiency in the effectiveness of detoxification of inhaled irritants and products of oxidative stress such as reactive oxygen species (ROS). Our case-control studies show that polymorphisms at the glutathione S-transferase, GSTP1, locus on chromosome 11q13 may account for variation in host response to oxidative stress, a key component of airway inflammation. Frequency of the GSTP1 Val/Val genotype is reduced in atopic subjects compared with nonatopic subjects. Trend analysis also shows a significant decrease of GSTP1 Val/Val (with parallel increase of GSTP1 Ile/Ile) genotype frequency with increasing severity of airflow obstruction/bronchial hyperresponsiveness. The implication of specific polymorphisms at the GSTP1 locus in airway inflammation is entirely novel: however, GST are recognized as a supergene family of enzymes critical in 1) cell protection from the toxic products of ROS-mediated reactions, 2) modulation of eicosanoid synthesis.. airway inflammation| atopy| bronchial hyperresponsiveness| gstp1 polymorphisms|polycyclic aromatic-hydrocarbons| human-lung| nitrogen-dioxide| diol epoxides| expression| exposure| asthma| ozone| purification| association.	2000	airway inflammation| atopy| bronchial hyperresponsiveness| gstp1 polymorphisms|polycyclic aromatic-hydrocarbons| human-lung| nitrogen-dioxide| diol epoxides| expression| exposure| asthma| ozone| purification| association	Spiteri, MA; Bianco, A; Strange, RC; Fryer, AA	Polymorphisms at the glutathione S-transferase, GSTP1 locus: a novel mechanism for susceptibility and development of atopic airway inflammation		ALLERGY	airway inflammation; atopy; bronchial hyperresponsiveness; GSTP1 polymorphisms	POLYCYCLIC AROMATIC-HYDROCARBONS; HUMAN-LUNG; NITROGEN-DIOXIDE; DIOL EPOXIDES; EXPRESSION; EXPOSURE; ASTHMA; OZONE; PURIFICATION; ASSOCIATION	A common feature of environmental irritants is their ability to cause local inflammation which could alter airway function. The principal targets of such injury are the epithelial cells lining the airway passages and the lower respiratory gas-exchange areas. While host atopy is a recognized risk factor for airway inflammation, atopy alone cannot cause asthma. We hypothesize that susceptibility to persistent airway inflammation in atopic individuals is characterized by an inherited deficiency in the effectiveness of detoxification of inhaled irritants and products of oxidative stress such as reactive oxygen species (ROS). Our case-control studies show that polymorphisms at the glutathione S-transferase, GSTP1, locus on chromosome 11q13 may account for variation in host response to oxidative stress, a key component of airway inflammation. Frequency of the GSTP1 Val/Val genotype is reduced in atopic subjects compared with nonatopic subjects. Trend analysis also shows a significant decrease of GSTP1 Val/Val (with parallel increase of GSTP1 Ile/Ile) genotype frequency with increasing severity of airflow obstruction/bronchial hyperresponsiveness. The implication of specific polymorphisms at the GSTP1 locus in airway inflammation is entirely novel: however, GST are recognized as a supergene family of enzymes critical in 1) cell protection from the toxic products of ROS-mediated reactions, 2) modulation of eicosanoid synthesis.	27	85	2000	6	10.1034/j.1398-9995.2000.00502.x	Allergy; Immunology
Inhalable Microorganisms in Beijing's PM2.5 and PM10 Pollutants during a Severe Smog Event. Particulate matter (PM) air pollution poses a formidable public health threat to the city of Beijing. Among the various hazards of PM pollutants, microorganisms in PM2.5 and PM10 are thought to be responsible for various allergies and for the spread of respiratory diseases. While the physical and chemical properties of PM pollutants have been extensively studied, much less is known about the inhalable microorganisms. Most existing data on airborne microbial communities using 16S or 18S rRNA gene sequencing to categorize bacteria or fungi into the family or genus levels do not provide information on their allergenic and pathogenic potentials. Here we employed metagenomic methods to analyze the microbial composition of Beijing's PM pollutants during a severe January smog event. We show that with sufficient sequencing depth, airborne microbes including bacteria, archaea, fungi, and dsDNA viruses can be identified at the species level. Our results suggested that the majority of the inhalable microorganisms were soil-associated and nonpathogenic to human. Nevertheless, the sequences of several respiratory microbial allergens and pathogens were identified and their relative abundance appeared to have increased with increased concentrations of PM pollution. Our findings may serve as an important reference for environmental scientists, health workers, and city planners.. airborne bacterial communities| particulate matter| oxidative damage| air-pollution| united-states| clean-air| health| china| variability| size.	FEB 4-2014	airborne bacterial communities| particulate matter| oxidative damage| air-pollution| united-states| clean-air| health| china| variability| size	Cao, C; Jiang, WJ; Wang, BY; Fang, JH; Lang, JD; Tian, G; Jiang, JK; Zhu, TF	Inhalable Microorganisms in Beijing's PM2.5 and PM10 Pollutants during a Severe Smog Event		ENVIRONMENTAL SCIENCE & TECHNOLOGY		AIRBORNE BACTERIAL COMMUNITIES; PARTICULATE MATTER; OXIDATIVE DAMAGE; AIR-POLLUTION; UNITED-STATES; CLEAN-AIR; HEALTH; CHINA; VARIABILITY; SIZE	Particulate matter (PM) air pollution poses a formidable public health threat to the city of Beijing. Among the various hazards of PM pollutants, microorganisms in PM2.5 and PM10 are thought to be responsible for various allergies and for the spread of respiratory diseases. While the physical and chemical properties of PM pollutants have been extensively studied, much less is known about the inhalable microorganisms. Most existing data on airborne microbial communities using 16S or 18S rRNA gene sequencing to categorize bacteria or fungi into the family or genus levels do not provide information on their allergenic and pathogenic potentials. Here we employed metagenomic methods to analyze the microbial composition of Beijing's PM pollutants during a severe January smog event. We show that with sufficient sequencing depth, airborne microbes including bacteria, archaea, fungi, and dsDNA viruses can be identified at the species level. Our results suggested that the majority of the inhalable microorganisms were soil-associated and nonpathogenic to human. Nevertheless, the sequences of several respiratory microbial allergens and pathogens were identified and their relative abundance appeared to have increased with increased concentrations of PM pollution. Our findings may serve as an important reference for environmental scientists, health workers, and city planners.	45	84	2014	9	10.1021/es4048472	Engineering; Environmental Sciences & Ecology
The protective effect of farm milk consumption on childhood asthma and atopy: The GABRIELA study. Background: Farm milk consumption has been identified as an exposure that might contribute to the protective effect of farm life on childhood asthma and allergies. The mechanism of action and the role of particular constituents of farm milk, however, are not yet clear. Objective: We sought to investigate the farm milk effect and determine responsible milk constituents. Methods: In rural regions of Germany, Austria, and Switzerland, a comprehensive questionnaire about farm milk consumption and other farm-related exposures was completed by parents of 8334 school-aged children, and 7606 of them provided serum samples to assess specific IgE levels. In 800 cow's milk samples collected at the participants' homes, viable bacterial counts, whey protein levels, and total fat content were analyzed. Asthma, atopy, and hay fever were associated to reported milk consumption and for the first time to objectively measured milk constituents by using multiple regression analyses. Results: Reported raw milk consumption was inversely associated to asthma (adjusted odds ratio [aOR], 0.59; 95% CI, 0.46-0.74), atopy (aOR, 0.74; 95% CI, 0.61-0.90), and hay fever (aOR, 0.51; 95% CI, 0.37-0.69) independent of other farm exposures. Boiled farm milk did not show a protective effect. Total viable bacterial counts and total fat content of milk were not significantly related to asthma or atopy. Increased levels of the whey proteins BSA (aOR for highest vs lowest levels and asthma, 0.53; 95% CI, 0.30-0.97), alpha-lactalbumin (aOR for interquartile range and asthma, 0.71; 95% CI, 0.52-0.97), and beta-lactoglobulin (aOR for interquartile range and asthma, 0.62; 95% CI, 0.39-0.97), however, were inversely associated with asthma but not with atopy. Conclusions: The findings suggest that the protective effect of raw milk consumption on asthma might be associated with the whey protein fraction of milk. (J Allergy Clin Immunol 2011;128:766-73.). allergic diseases| asthma| atopy| children| farming| hay fever| microorganism| farm milk| risk| whey protein|school-age-children| inverse association| innate immunity| exposure| allergy| health| beta| life| prevalence| expression.	OCT-2011	allergic diseases| asthma| atopy| children| farming| hay fever| microorganism| farm milk| risk| whey protein|school-age-children| inverse association| innate immunity| exposure| allergy| health| beta| life| prevalence| expression	Loss, G; Apprich, S; Waser, M; Kneifel, W; Genuneit, J; Buchele, G; Weber, J; Sozanska, B; Danielewicz, H; Horak, E; van Neerven, RJJ; Heederik, D; Lorenzen, PC; von Mutius, E; Braun-Fahrlander, C	The protective effect of farm milk consumption on childhood asthma and atopy: The GABRIELA study		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Allergic diseases; asthma; atopy; children; farming; hay fever; microorganism; farm milk; risk; whey protein	SCHOOL-AGE-CHILDREN; INVERSE ASSOCIATION; INNATE IMMUNITY; EXPOSURE; ALLERGY; HEALTH; BETA; LIFE; PREVALENCE; EXPRESSION	Background: Farm milk consumption has been identified as an exposure that might contribute to the protective effect of farm life on childhood asthma and allergies. The mechanism of action and the role of particular constituents of farm milk, however, are not yet clear. Objective: We sought to investigate the farm milk effect and determine responsible milk constituents. Methods: In rural regions of Germany, Austria, and Switzerland, a comprehensive questionnaire about farm milk consumption and other farm-related exposures was completed by parents of 8334 school-aged children, and 7606 of them provided serum samples to assess specific IgE levels. In 800 cow's milk samples collected at the participants' homes, viable bacterial counts, whey protein levels, and total fat content were analyzed. Asthma, atopy, and hay fever were associated to reported milk consumption and for the first time to objectively measured milk constituents by using multiple regression analyses. Results: Reported raw milk consumption was inversely associated to asthma (adjusted odds ratio [aOR], 0.59; 95% CI, 0.46-0.74), atopy (aOR, 0.74; 95% CI, 0.61-0.90), and hay fever (aOR, 0.51; 95% CI, 0.37-0.69) independent of other farm exposures. Boiled farm milk did not show a protective effect. Total viable bacterial counts and total fat content of milk were not significantly related to asthma or atopy. Increased levels of the whey proteins BSA (aOR for highest vs lowest levels and asthma, 0.53; 95% CI, 0.30-0.97), alpha-lactalbumin (aOR for interquartile range and asthma, 0.71; 95% CI, 0.52-0.97), and beta-lactoglobulin (aOR for interquartile range and asthma, 0.62; 95% CI, 0.39-0.97), however, were inversely associated with asthma but not with atopy. Conclusions: The findings suggest that the protective effect of raw milk consumption on asthma might be associated with the whey protein fraction of milk. (J Allergy Clin Immunol 2011;128:766-73.)	32	84	2011	12	10.1016/j.jaci.2011.07.048	Allergy; Immunology
An Official American Thoracic Society Statement: Work-Exacerbated Asthma. Rationale: Occupational exposures can contribute to the exacerbation as well as the onset of asthma. However, work-exacerbated asthma (WEA) has received less attention than occupational asthma (OA) that is caused by work. Objectives: The purpose of this Statement is to summarize current knowledge about the descriptive epidemiology, clinical characteristics, and management and treatment of WEA; propose a case definition for WEA; and discuss needs for prevention and research. Methods: Information about WEA was identified primarily by systematic searches of the medical literature. Statements about prevention and research needs were reached by consensus. Measurements and Main Results: WEA is defined as the worsening of asthma due to conditions at work. WEA is common, with a median prevalence of 21.5% among adults with asthma. Different types of agents or conditions at work may exacerbate asthma. WEA cases with persistent work-related symptoms can have clinical characteristics (level of severity, medication needs) and adverse socioeconomic outcomes (unemployment, reduction in income) similar to those of OA cases. Compared with adults with asthma unrelated to work, WEA cases report more days with symptoms, seek more medical care, and have a lower quality of life. WEA should be considered in any patient with asthma that is getting worse or who has work-related symptoms. Management of WEA should focus on reducing work exposures and optimizing standard medical management, with a change in jobs only if these measures are not successful. Conclusions: WEA is a common and under recognized adverse outcome resulting from conditions at work. Additional research is needed to improve the understanding of the risk factors for, and mechanisms and outcomes of, WEA, and to inform and evaluate preventive interventions.. asthma| occupational diseases| work-related asthma| exacerbation| work-exacerbated asthma|quality-of-life| diagnosing occupational asthma| workplace exacerbation| lung-function| airway inflammation| chronic-bronchitis| respiratory-tract| signaling cascade| sulfur-dioxide| induced sputum.	AUG 1-2011	asthma| occupational diseases| work-related asthma| exacerbation| work-exacerbated asthma|quality-of-life| diagnosing occupational asthma| workplace exacerbation| lung-function| airway inflammation| chronic-bronchitis| respiratory-tract| signaling cascade| sulfur-dioxide| induced sputum	Henneberger, PK; Redlich, CA; Callahan, DB; Harber, P; Lemiere, C; Martin, J; Tarlo, SM; Vandenplas, O; Toren, K	An Official American Thoracic Society Statement: Work-Exacerbated Asthma		AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE	asthma; occupational diseases; work-related asthma; exacerbation; work-exacerbated asthma	QUALITY-OF-LIFE; DIAGNOSING OCCUPATIONAL ASTHMA; WORKPLACE EXACERBATION; LUNG-FUNCTION; AIRWAY INFLAMMATION; CHRONIC-BRONCHITIS; RESPIRATORY-TRACT; SIGNALING CASCADE; SULFUR-DIOXIDE; INDUCED SPUTUM	Rationale: Occupational exposures can contribute to the exacerbation as well as the onset of asthma. However, work-exacerbated asthma (WEA) has received less attention than occupational asthma (OA) that is caused by work. Objectives: The purpose of this Statement is to summarize current knowledge about the descriptive epidemiology, clinical characteristics, and management and treatment of WEA; propose a case definition for WEA; and discuss needs for prevention and research. Methods: Information about WEA was identified primarily by systematic searches of the medical literature. Statements about prevention and research needs were reached by consensus. Measurements and Main Results: WEA is defined as the worsening of asthma due to conditions at work. WEA is common, with a median prevalence of 21.5% among adults with asthma. Different types of agents or conditions at work may exacerbate asthma. WEA cases with persistent work-related symptoms can have clinical characteristics (level of severity, medication needs) and adverse socioeconomic outcomes (unemployment, reduction in income) similar to those of OA cases. Compared with adults with asthma unrelated to work, WEA cases report more days with symptoms, seek more medical care, and have a lower quality of life. WEA should be considered in any patient with asthma that is getting worse or who has work-related symptoms. Management of WEA should focus on reducing work exposures and optimizing standard medical management, with a change in jobs only if these measures are not successful. Conclusions: WEA is a common and under recognized adverse outcome resulting from conditions at work. Additional research is needed to improve the understanding of the risk factors for, and mechanisms and outcomes of, WEA, and to inform and evaluate preventive interventions.	77	84	2011	11	10.1164/rccm.812011ST	General & Internal Medicine; Respiratory System
Breast-feeding in relation to asthma, lung function, and sensitization in young schoolchildren. Background: The evidence from previous studies on beneficial effects of breast-feeding in relation to development of asthma is conflicting. Objective: To investigate the relation between breast-feeding and asthma and/or sensitization during the first 8 years of life. Method: In a birth cohort, children were followed up to 8 years by questionnaires at ages 2 months and 1, 2, 4, and 8 years to collect information on exposures and health effects. Determination of serum IgE antibodies to common inhalant and food allergens was performed at 4 and 8 years. Longitudinal analyses were applied by using general estimated equations. The study population consisted of 3825 children (93% of the original cohort), of whom 2370 gave blood and 2564 performed lung function measurements at 8 years. Results: Children exclusively breast-fed 4 months or more had a reduced risk of asthma during the first 8 years of life (adjusted odds ratio [OR], 0.63; 95% CI, 0.50-0.78) compared with children breast-fed less than 4 months. At 8 years, reduced risks of sensitization (adjusted OR, 0.79; 95% CI, 0.64-0.99) and asthma in combination with sensitization (adjusted OR, 0.59; 95% CI, 0.37-0.93) were seen among children exclusively breast-fed 4 months or more. This group also had a significantly better lung function measured with peak expiratory flow. Conclusion: Breast-feeding for 4 months or more seems to reduce the risk of asthma up to 8 years. At this age, a reduced risk was observed particularly for asthma combined with sensitization. Furthermore, breast-feeding seems to have a beneficial effect on lung function. (J Allergy Clin Immunol 2010;125:1013-9.). breast-feeding| asthma| sensitization| lung function| infant feeding| prevention| bamse|prospective birth cohort| allergic diseases| childhood asthma| atopic disease| risk| children| wheeze| life| prevention| phenotypes.	MAY-2010	breast-feeding| asthma| sensitization| lung function| infant feeding| prevention| bamse|prospective birth cohort| allergic diseases| childhood asthma| atopic disease| risk| children| wheeze| life| prevention| phenotypes	Kull, I; Melen, E; Alm, J; Hallberg, J; Svartengren, M; van Hage, M; Pershagen, G; Wickman, M; Bergstrom, A	Breast-feeding in relation to asthma, lung function, and sensitization in young schoolchildren		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	Breast-feeding; asthma; sensitization; lung function; infant feeding; prevention; BAMSE	PROSPECTIVE BIRTH COHORT; ALLERGIC DISEASES; CHILDHOOD ASTHMA; ATOPIC DISEASE; RISK; CHILDREN; WHEEZE; LIFE; PREVENTION; PHENOTYPES	Background: The evidence from previous studies on beneficial effects of breast-feeding in relation to development of asthma is conflicting. Objective: To investigate the relation between breast-feeding and asthma and/or sensitization during the first 8 years of life. Method: In a birth cohort, children were followed up to 8 years by questionnaires at ages 2 months and 1, 2, 4, and 8 years to collect information on exposures and health effects. Determination of serum IgE antibodies to common inhalant and food allergens was performed at 4 and 8 years. Longitudinal analyses were applied by using general estimated equations. The study population consisted of 3825 children (93% of the original cohort), of whom 2370 gave blood and 2564 performed lung function measurements at 8 years. Results: Children exclusively breast-fed 4 months or more had a reduced risk of asthma during the first 8 years of life (adjusted odds ratio [OR], 0.63; 95% CI, 0.50-0.78) compared with children breast-fed less than 4 months. At 8 years, reduced risks of sensitization (adjusted OR, 0.79; 95% CI, 0.64-0.99) and asthma in combination with sensitization (adjusted OR, 0.59; 95% CI, 0.37-0.93) were seen among children exclusively breast-fed 4 months or more. This group also had a significantly better lung function measured with peak expiratory flow. Conclusion: Breast-feeding for 4 months or more seems to reduce the risk of asthma up to 8 years. At this age, a reduced risk was observed particularly for asthma combined with sensitization. Furthermore, breast-feeding seems to have a beneficial effect on lung function. (J Allergy Clin Immunol 2010;125:1013-9.)	39	84	2010	7	10.1016/j.jaci.2010.01.051	Allergy; Immunology
Parental stress increases the effect of traffic-related air pollution on childhood asthma incidence. Exposure to traffic-related pollution (TRP) and tobacco smoke have been associated with new onset asthma in children. Psychosocial stress-related susceptibility has been proposed to explain social disparities in asthma. We investigated whether low socioeconomic status (SES) or high parental stress modified the effect of TRP and in utero tobacco smoke exposure on new onset asthma. We identified 2,497 children aged 5-9 years with no history of asthma or wheeze at study entry (2002-2003) into the Children's Health Study, a prospective cohort study in southern California. The primary outcome was parental report of doctor-diagnosed new onset asthma during 3 years of follow-up. Residential exposure to TRP was assessed using a line source dispersion model. Information about maternal smoking during pregnancy, parental education (a proxy for SES), and parental stress were collected in the study baseline questionnaire. The risk of asthma attributable to TRP was significantly higher for subjects with high parental stress (HR 1.51 across the interquartile range for TRP; 95% CI 1.16-1.96) than for subjects with low parental stress (HR 1.05, 95% CI 0.74-1.49; interaction P value 0.05). Stress also was associated with larger effects of in utero tobacco smoke. A similar pattern of increased risk of asthma was observed among children from low SES families who also were exposed to either TRP or in utero tobacco smoke. These results suggest that children from stressful households are more susceptible to the effects of TRP and in utero tobacco smoke on the development of asthma.. socioeconomic status| tobacco smoke|environmental tobacco-smoke| diesel exhaust particles| maternal smoking| socioeconomic-status| lung-function| in-vivo| respiratory health| prospective cohort| risk-factors| children.	JUL 28-2009	socioeconomic status| tobacco smoke|environmental tobacco-smoke| diesel exhaust particles| maternal smoking| socioeconomic-status| lung-function| in-vivo| respiratory health| prospective cohort| risk-factors| children	Shankardass, K; McConnell, R; Jerrett, M; Milam, J; Richardson, J; Berhane, K	Parental stress increases the effect of traffic-related air pollution on childhood asthma incidence		PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA	socioeconomic status; tobacco smoke	ENVIRONMENTAL TOBACCO-SMOKE; DIESEL EXHAUST PARTICLES; MATERNAL SMOKING; SOCIOECONOMIC-STATUS; LUNG-FUNCTION; IN-VIVO; RESPIRATORY HEALTH; PROSPECTIVE COHORT; RISK-FACTORS; CHILDREN	Exposure to traffic-related pollution (TRP) and tobacco smoke have been associated with new onset asthma in children. Psychosocial stress-related susceptibility has been proposed to explain social disparities in asthma. We investigated whether low socioeconomic status (SES) or high parental stress modified the effect of TRP and in utero tobacco smoke exposure on new onset asthma. We identified 2,497 children aged 5-9 years with no history of asthma or wheeze at study entry (2002-2003) into the Children's Health Study, a prospective cohort study in southern California. The primary outcome was parental report of doctor-diagnosed new onset asthma during 3 years of follow-up. Residential exposure to TRP was assessed using a line source dispersion model. Information about maternal smoking during pregnancy, parental education (a proxy for SES), and parental stress were collected in the study baseline questionnaire. The risk of asthma attributable to TRP was significantly higher for subjects with high parental stress (HR 1.51 across the interquartile range for TRP; 95% CI 1.16-1.96) than for subjects with low parental stress (HR 1.05, 95% CI 0.74-1.49; interaction P value 0.05). Stress also was associated with larger effects of in utero tobacco smoke. A similar pattern of increased risk of asthma was observed among children from low SES families who also were exposed to either TRP or in utero tobacco smoke. These results suggest that children from stressful households are more susceptible to the effects of TRP and in utero tobacco smoke on the development of asthma.	72	84	2009	6	10.1073/pnas.0812910106	Science & Technology - Other Topics
Clinical Severity Correlates with Impaired Barrier in Filaggrin-Related Eczema. Mutations in the gene-encoding filaggrin (FLG), a key molecule involved in skin barrier function, have been shown to be a major predisposing factor for atopic dermatitis (AD; eczema). To elucidate the pathomechanisms underlying filaggrin-related AD, we investigated stratum corneum (SC) hydration and transepidermal water loss (TEWL) as parameters of barrier function in AD patients harboring FLG mutations compared to AD patients without any FLG mutation. In filaggrin-related AD, SC hydration was both significantly reduced ( P < 0.01-0.05) and thicker (P < 0.01-0.05) than that in healthy controls. TEWL was demonstrably increased in non-filaggrin AD compared to healthy controls ( P < 0.01-0.05). The objective score of atopic dermatitis (OSCORAD), a disease clinical severity index, significantly correlated with TEWL (r = 0.81, P < 0.005), SC hydration (r = -0.65, P < 0.05), and SC thickness (r = 0.59, P < 0.05) in filaggrin-related AD. On the contrary, there was no correlation between these parameters and the OSCORAD in non-filaggrin AD. Furthermore, a significant correlation was obtained between the OSCORAD and specific IgE for house dust (r = 0.66, P < 0.05), mite allergen (r = 0.53, P < 0.05), and cat dander (r = 0.64, P < 0.05) in filaggrin-related AD, but not in non-filaggrin AD. All these data suggest that experimentally demonstrable skin barrier defects due to FLG mutations may play a crucial role in the pathogenesis of AD.. stratum-corneum hydration| cause ichthyosis vulgaris| atopic-dermatitis| uninvolved skin| gene| mutations| penetration| disease.	MAR-2009	stratum-corneum hydration| cause ichthyosis vulgaris| atopic-dermatitis| uninvolved skin| gene| mutations| penetration| disease	Nemoto-Hasebe, I; Akiyama, M; Nomura, T; Sandilands, A; McLean, WHI; Shimizu, H	Clinical Severity Correlates with Impaired Barrier in Filaggrin-Related Eczema		JOURNAL OF INVESTIGATIVE DERMATOLOGY		STRATUM-CORNEUM HYDRATION; CAUSE ICHTHYOSIS VULGARIS; ATOPIC-DERMATITIS; UNINVOLVED SKIN; GENE; MUTATIONS; PENETRATION; DISEASE	Mutations in the gene-encoding filaggrin (FLG), a key molecule involved in skin barrier function, have been shown to be a major predisposing factor for atopic dermatitis (AD; eczema). To elucidate the pathomechanisms underlying filaggrin-related AD, we investigated stratum corneum (SC) hydration and transepidermal water loss (TEWL) as parameters of barrier function in AD patients harboring FLG mutations compared to AD patients without any FLG mutation. In filaggrin-related AD, SC hydration was both significantly reduced ( P < 0.01-0.05) and thicker (P < 0.01-0.05) than that in healthy controls. TEWL was demonstrably increased in non-filaggrin AD compared to healthy controls ( P < 0.01-0.05). The objective score of atopic dermatitis (OSCORAD), a disease clinical severity index, significantly correlated with TEWL (r = 0.81, P < 0.005), SC hydration (r = -0.65, P < 0.05), and SC thickness (r = 0.59, P < 0.05) in filaggrin-related AD. On the contrary, there was no correlation between these parameters and the OSCORAD in non-filaggrin AD. Furthermore, a significant correlation was obtained between the OSCORAD and specific IgE for house dust (r = 0.66, P < 0.05), mite allergen (r = 0.53, P < 0.05), and cat dander (r = 0.64, P < 0.05) in filaggrin-related AD, but not in non-filaggrin AD. All these data suggest that experimentally demonstrable skin barrier defects due to FLG mutations may play a crucial role in the pathogenesis of AD.	25	84	2009	8	10.1038/jid.2008.280	Dermatology
Maternal smoking during pregnancy and children's cognitive and physical development: A causal risk factor?. There remains considerable debate regarding the effects of maternal smoking during pregnancy on children's growth and development. Evidence that exposure to maternal smoking during pregnancy is associated with numerous adverse outcomes is contradicted by research suggesting that these associations are spurious. The authors investigated the relation between maternal smoking during pregnancy and 14 developmental outcomes of children from birth through age 7 years, using data from the Collaborative Perinatal Project (1959-1974; n = 52,919). In addition to adjusting for potential confounders measured contemporaneously with maternal smoking, the authors fitted conditional fixed-effects models among siblings that controlled for unmeasured confounders. Results from the conditional analyses indicated a birth weight difference of -85.63 g associated with smoking of >= 20 cigarettes daily during pregnancy (95% confidence interval: -131.91, -39.34) and 2.73 times' higher odds of being overweight at age 7 years (95% confidence interval: 1.30, 5.71). However, the associations between maternal smoking and 12 other outcomes studied (including Apgar score, intelligence, academic achievement, conduct problems, and asthma) were entirely eliminated after adjustment for measured and unmeasured confounders. The authors conclude that the hypothesized effects of maternal smoking during pregnancy on these outcomes either are not present or are not distinguishable from a broader range of familial factors associated with maternal smoking.. child| child development| cognition| growth| intelligence| pregnancy| smoking|cigarette-smoking| childhood| exposure| outcomes| age| psychopathology| intelligence| association| performance| population.	SEP 1-2008	child| child development| cognition| growth| intelligence| pregnancy| smoking|cigarette-smoking| childhood| exposure| outcomes| age| psychopathology| intelligence| association| performance| population	Gilman, SE; Gardener, H; Buka, SL	Maternal smoking during pregnancy and children's cognitive and physical development: A causal risk factor?		AMERICAN JOURNAL OF EPIDEMIOLOGY	child; child development; cognition; growth; intelligence; pregnancy; smoking	CIGARETTE-SMOKING; CHILDHOOD; EXPOSURE; OUTCOMES; AGE; PSYCHOPATHOLOGY; INTELLIGENCE; ASSOCIATION; PERFORMANCE; POPULATION	There remains considerable debate regarding the effects of maternal smoking during pregnancy on children's growth and development. Evidence that exposure to maternal smoking during pregnancy is associated with numerous adverse outcomes is contradicted by research suggesting that these associations are spurious. The authors investigated the relation between maternal smoking during pregnancy and 14 developmental outcomes of children from birth through age 7 years, using data from the Collaborative Perinatal Project (1959-1974; n = 52,919). In addition to adjusting for potential confounders measured contemporaneously with maternal smoking, the authors fitted conditional fixed-effects models among siblings that controlled for unmeasured confounders. Results from the conditional analyses indicated a birth weight difference of -85.63 g associated with smoking of >= 20 cigarettes daily during pregnancy (95% confidence interval: -131.91, -39.34) and 2.73 times' higher odds of being overweight at age 7 years (95% confidence interval: 1.30, 5.71). However, the associations between maternal smoking and 12 other outcomes studied (including Apgar score, intelligence, academic achievement, conduct problems, and asthma) were entirely eliminated after adjustment for measured and unmeasured confounders. The authors conclude that the hypothesized effects of maternal smoking during pregnancy on these outcomes either are not present or are not distinguishable from a broader range of familial factors associated with maternal smoking.	53	84	2008	10	10.1093/aje/kwn175	Public, Environmental & Occupational Health
Airway injury as a mechanism for exercise-induced bronchoconstriction in elite athletes. Exercise-induced bronchoconstriction (EIB) is a consequence of evaporative water loss in conditioning the inspired air. The water loss causes cooling and dehydration of the airway surface. One acute effect of dehydration is the release of mediators, such as prostaglandins, leukotrienes, and histamine, that can stimulate smooth muscle, causing contraction and a change in vascular permeability. Inspiring cold air increases dehydration of the surface area and causes changes in bronchial blood flow. This article proposes that the pathogenesis of EIB in elite athletes relates to the epithelial injury arising from breathing poorly conditioned air at high flows for long periods of time or high volumes of irritant particles or gases. The evidence to support this proposal comes from many markers of injury. The restorative process after injury involves plasma exudation and movement of cells into the airways, a process repeated many times during a season of training. This process has the potential to expose smooth muscle to a wide variety of plasma- and cell-derived substances. The exposure to these substances over time can lead to an alteration in the contractile properties of the smooth muscle, making it more sensitive to mediators of bronchoconstriction. It is proposed that cold-weather athletes have airway hyperresponsiveness (AHR) to pharmacollogic agents as a result of epithelial injury. In those who are allergic, AIIR can also be expressed as EIB. The role of beta(2)-receptor agonists in inhibiting and enhancing the development of AHR and EIB is discussed.. epithelial injury| airway smooth muscle| mast cells| microvascular permeability| eicosanoids| beta(2)-agonists|cross-country skiers| chlorinated swimming pools| fish-oil supplementation| induced plasma exudation| mast-cell activation| induced asthma| induced bronchospasm| bronchial hyperresponsiveness| smooth-muscle| passive sensitization.	AUG-2008	epithelial injury| airway smooth muscle| mast cells| microvascular permeability| eicosanoids| beta(2)-agonists|cross-country skiers| chlorinated swimming pools| fish-oil supplementation| induced plasma exudation| mast-cell activation| induced asthma| induced bronchospasm| bronchial hyperresponsiveness| smooth-muscle| passive sensitization	Anderson, SD; Kippelen, P	Airway injury as a mechanism for exercise-induced bronchoconstriction in elite athletes		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	epithelial injury; airway smooth muscle; mast cells; microvascular permeability; eicosanoids; beta(2)-agonists	CROSS-COUNTRY SKIERS; CHLORINATED SWIMMING POOLS; FISH-OIL SUPPLEMENTATION; INDUCED PLASMA EXUDATION; MAST-CELL ACTIVATION; INDUCED ASTHMA; INDUCED BRONCHOSPASM; BRONCHIAL HYPERRESPONSIVENESS; SMOOTH-MUSCLE; PASSIVE SENSITIZATION	Exercise-induced bronchoconstriction (EIB) is a consequence of evaporative water loss in conditioning the inspired air. The water loss causes cooling and dehydration of the airway surface. One acute effect of dehydration is the release of mediators, such as prostaglandins, leukotrienes, and histamine, that can stimulate smooth muscle, causing contraction and a change in vascular permeability. Inspiring cold air increases dehydration of the surface area and causes changes in bronchial blood flow. This article proposes that the pathogenesis of EIB in elite athletes relates to the epithelial injury arising from breathing poorly conditioned air at high flows for long periods of time or high volumes of irritant particles or gases. The evidence to support this proposal comes from many markers of injury. The restorative process after injury involves plasma exudation and movement of cells into the airways, a process repeated many times during a season of training. This process has the potential to expose smooth muscle to a wide variety of plasma- and cell-derived substances. The exposure to these substances over time can lead to an alteration in the contractile properties of the smooth muscle, making it more sensitive to mediators of bronchoconstriction. It is proposed that cold-weather athletes have airway hyperresponsiveness (AHR) to pharmacollogic agents as a result of epithelial injury. In those who are allergic, AIIR can also be expressed as EIB. The role of beta(2)-receptor agonists in inhibiting and enhancing the development of AHR and EIB is discussed.	163	84	2008	11	10.1016/j.jaci.2008.05.001	Allergy; Immunology
Prenatal exposure to a farm environment modifies atopic sensitization at birth. Background: Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school age. Objective: We sought to evaluate the effects of maternal exposure to animal sheds and other farm-related exposures during pregnancy on cord blood IgE levels in a prospective birth cohort. Methods: Pregnant women living in rural areas in Austria, Finland, France, Germany, and Switzerland were recruited in the third trimester of pregnancy. Information on maternal farm-related exposures, nutrition, and health during pregnancy was obtained by means of interviews. Specific IgE levels for food and common inhalant allergens were assessed in cord blood of 922 children and peripheral blood samples of their mothers. Results: Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow's milk independently from maternal IgE. In contrast, there was an inverse relationship between maternal exposure to animal sheds and cord blood IgE levels against seasonal allergens (adjusted odds ratio, 0.38; 95% CI, 0.21-0.70). This association was not confounded by maternal IgE levels. Maternal contact with hay enhanced the protective effect of exposure to animal sheds on IgE levels to grass pollen in cord blood.. prenatal exposure| atopic sensitization| cord blood| farming| microbial components|house-dust| allergic diseases| early-life| children| asthma| parsifal| project.	AUG-2008	prenatal exposure| atopic sensitization| cord blood| farming| microbial components|house-dust| allergic diseases| early-life| children| asthma| parsifal| project	Ege, MJ; Herzum, I; Buchele, G; Krauss-Etschmann, S; Lauener, RP; Roponen, M; Hyvarinen, A; Vuitton, DA; Riedler, J; Brunekreef, B; Dalphin, JC; Braun-Fahrlander, C; Pekkanen, J; Renz, H; von Mutius, E	Prenatal exposure to a farm environment modifies atopic sensitization at birth		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	prenatal exposure; atopic sensitization; cord blood; farming; microbial components	HOUSE-DUST; ALLERGIC DISEASES; EARLY-LIFE; CHILDREN; ASTHMA; PARSIFAL; PROJECT	Background: Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school age. Objective: We sought to evaluate the effects of maternal exposure to animal sheds and other farm-related exposures during pregnancy on cord blood IgE levels in a prospective birth cohort. Methods: Pregnant women living in rural areas in Austria, Finland, France, Germany, and Switzerland were recruited in the third trimester of pregnancy. Information on maternal farm-related exposures, nutrition, and health during pregnancy was obtained by means of interviews. Specific IgE levels for food and common inhalant allergens were assessed in cord blood of 922 children and peripheral blood samples of their mothers. Results: Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow's milk independently from maternal IgE. In contrast, there was an inverse relationship between maternal exposure to animal sheds and cord blood IgE levels against seasonal allergens (adjusted odds ratio, 0.38; 95% CI, 0.21-0.70). This association was not confounded by maternal IgE levels. Maternal contact with hay enhanced the protective effect of exposure to animal sheds on IgE levels to grass pollen in cord blood.	27	84	2008	6	10.1016/j.jaci.2008.06.011	Allergy; Immunology
Impairment of T-regulatory cells in cord blood of atopic mothers. Background: Maternal atopy is a strong predictor for the development of childhood allergic diseases. The underlying mechanisms are ill defined, yet regulatory T (Treg) and T(H)17 cells may play a key role potentially shaping the early immune system toward a proallergic or antiallergic immune regulation. Objective: We examined T(H)1/T(H)2, Treg, and T(H)17 cell responses to innate (lipid A/peptidoglycan) and mitogen/adaptive (phytohemagglutinin/Dermatophagoides pteronyssinus 1) immune stimulation in cord blood from offspring of atopic/nonatopic mothers. Methods: Cord blood mononuclear cells from 161 healthy neonates (59% nonatopic, 41% atopic mothers) were investigated regarding Treg and T(H)17 cells (mRNA/surface markers), suppressive function, and proliferation/cytokine secretion. Results: Cord blood from offspring of atopic mothers showed fewer innate-induced Treg cells (CD4(+)CD25(+) high), lower mRNA expression of associated markers (glucocorticoid-induced tumor necrosis factor receptor-related protein/lymphocyte activation gene 3; P < .05), and a trend toward lower Forkhead box transcription factor 3 (Foxp3) expression. Treg cell function was impaired in mitogen-induced suppression of T effector cells in cord blood of offspring from atopic mothers (P = .03). Furthermore, IL-10 and IFN-gamma secretion were decreased in innate-stimulated cord blood of offspring from atopic mothers (P = .04/.05). Innate-induced IL-17 was independent of maternal atopy and highly correlated with IL-13 secretion. Conclusion: In offspring of atopic mothers, Treg cell numbers, expression, and function were impaired at birth. T(H)17 cells were correlated with T(H)2 cells, independently of maternal atopy.. adaptive| cord blood| cytokines| innate| il| regulatory t cells| t(h)17 cells| toll-like receptor|neonatal immune-responses| school-age-children| expression| stimulation| exposure| asthma| inflammation| receptor-2| allergy| foxp3.	JUN-2008	adaptive| cord blood| cytokines| innate| il| regulatory t cells| t(h)17 cells| toll-like receptor|neonatal immune-responses| school-age-children| expression| stimulation| exposure| asthma| inflammation| receptor-2| allergy| foxp3	Schaub, B; Liu, J; Hoppler, S; Haug, S; Sattler, C; Lluis, A; Illi, S; von Mutius, E	Impairment of T-regulatory cells in cord blood of atopic mothers		JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY	adaptive; cord blood; cytokines; innate; IL; regulatory T cells; T(H)17 cells; Toll-like receptor	NEONATAL IMMUNE-RESPONSES; SCHOOL-AGE-CHILDREN; EXPRESSION; STIMULATION; EXPOSURE; ASTHMA; INFLAMMATION; RECEPTOR-2; ALLERGY; FOXP3	Background: Maternal atopy is a strong predictor for the development of childhood allergic diseases. The underlying mechanisms are ill defined, yet regulatory T (Treg) and T(H)17 cells may play a key role potentially shaping the early immune system toward a proallergic or antiallergic immune regulation. Objective: We examined T(H)1/T(H)2, Treg, and T(H)17 cell responses to innate (lipid A/peptidoglycan) and mitogen/adaptive (phytohemagglutinin/Dermatophagoides pteronyssinus 1) immune stimulation in cord blood from offspring of atopic/nonatopic mothers. Methods: Cord blood mononuclear cells from 161 healthy neonates (59% nonatopic, 41% atopic mothers) were investigated regarding Treg and T(H)17 cells (mRNA/surface markers), suppressive function, and proliferation/cytokine secretion. Results: Cord blood from offspring of atopic mothers showed fewer innate-induced Treg cells (CD4(+)CD25(+) high), lower mRNA expression of associated markers (glucocorticoid-induced tumor necrosis factor receptor-related protein/lymphocyte activation gene 3; P < .05), and a trend toward lower Forkhead box transcription factor 3 (Foxp3) expression. Treg cell function was impaired in mitogen-induced suppression of T effector cells in cord blood of offspring from atopic mothers (P = .03). Furthermore, IL-10 and IFN-gamma secretion were decreased in innate-stimulated cord blood of offspring from atopic mothers (P = .04/.05). Innate-induced IL-17 was independent of maternal atopy and highly correlated with IL-13 secretion. Conclusion: In offspring of atopic mothers, Treg cell numbers, expression, and function were impaired at birth. T(H)17 cells were correlated with T(H)2 cells, independently of maternal atopy.	25	84	2008	9	10.1016/j.jaci.2008.04.010	Allergy; Immunology
Chronic stress, salivary cortisol, and alpha-amylase in children with asthma and healthy children. The present study examined whether chronic stress is related to daily life levels of salivary a-amylase (sAA), a marker for sympathetic activity, and cortisol in healthy children versus children with asthma. Children's sAA and cortisol levels were measured repeatedly over 2 days. Chronic stress measures included interviews with children about chronic home life stress and interviews with parents about one marker of socioeconomic status, parental education. Among children with asthma, higher chronic stress was associated with lower daily sAA output, while among healthy children, higher chronic stress was associated with flatter cortisol slopes. In conclusion, chronically stressed children with asthma showed lower salivary a-amylase output, indicating lower sympathetic activity, and implying a possible mechanism for increased susceptibility to symptom exacerbations. In contrast, higher cortisol levels in healthy children with chronic stress may indicate, for example, an increased risk for infectious diseases. This dichotomy emphasizes the different biological effects of chronic stress depending on illness status. (c) 2007 Elsevier B.V. All tights reserved.. salivary alpha-amylase| cortisol| childhood asthma| chronic stress| socioeconomic status|three-mile-island| psychological stress| socioeconomic-status| psychosocial stress| adrenergic activity| beta(2)-adrenergic receptor| glucocorticoid-receptor| whole saliva| responses| immune.	APR-2008	salivary alpha-amylase| cortisol| childhood asthma| chronic stress| socioeconomic status|three-mile-island| psychological stress| socioeconomic-status| psychosocial stress| adrenergic activity| beta(2)-adrenergic receptor| glucocorticoid-receptor| whole saliva| responses| immune	Wolf, JM; Nicholls, E; Chen, E	Chronic stress, salivary cortisol, and alpha-amylase in children with asthma and healthy children		BIOLOGICAL PSYCHOLOGY	salivary alpha-amylase; cortisol; childhood asthma; chronic stress; socioeconomic status	THREE-MILE-ISLAND; PSYCHOLOGICAL STRESS; SOCIOECONOMIC-STATUS; PSYCHOSOCIAL STRESS; ADRENERGIC ACTIVITY; BETA(2)-ADRENERGIC RECEPTOR; GLUCOCORTICOID-RECEPTOR; WHOLE SALIVA; RESPONSES; IMMUNE	The present study examined whether chronic stress is related to daily life levels of salivary a-amylase (sAA), a marker for sympathetic activity, and cortisol in healthy children versus children with asthma. Children's sAA and cortisol levels were measured repeatedly over 2 days. Chronic stress measures included interviews with children about chronic home life stress and interviews with parents about one marker of socioeconomic status, parental education. Among children with asthma, higher chronic stress was associated with lower daily sAA output, while among healthy children, higher chronic stress was associated with flatter cortisol slopes. In conclusion, chronically stressed children with asthma showed lower salivary a-amylase output, indicating lower sympathetic activity, and implying a possible mechanism for increased susceptibility to symptom exacerbations. In contrast, higher cortisol levels in healthy children with chronic stress may indicate, for example, an increased risk for infectious diseases. This dichotomy emphasizes the different biological effects of chronic stress depending on illness status. (c) 2007 Elsevier B.V. All tights reserved.	69	84	2008	9	10.1016/j.biopsycho.2007.12.004	Psychology; Behavioral Sciences
Pollen proteolytic enzymes degrade tight junctions. Background and objective: Asthma and allergic rhinitis are significant, increasing causes of morbidity worldwide. Pollen, a major cause of seasonal rhinitis/conjunctivitis, carries proteolytic enzymes on its surface. We showed previously that peptidase allergens from house dust mites compromise epithelial barrier function by degrading the extracellular domains of the tight junction proteins, occludin and claudin, thus facilitating allergen delivery across epithelial layers. In this study, we aimed to determine whether peptidases from allergenic pollens should similarly be considered to have a role in disrupting tight junctions. Methods: Diffusates from stored pollen of Giant Ragweed, White Birch and Kentucky Blue Grass, and fresh pollen from Easter Lily were applied to confluent monolayers of Madin-Darby canine kidney (MDCK) and Calu-3 cells in serum-free medium. Immunofluorescence was performed for the tight junction proteins, occludin, claudin-1 and ZO-1. The effect of pollen diffusate on occludin was studied by Western blotting, and enzymatic activity in the diffusates was demonstrated by zymography. The ability of protease inhibitors to block the action of the diffusate on tight junctions was investigated. Results: Diffusates from all four allergenic pollens caused loss of immunofluorescence labelling for tight junction proteins on MDCK and Calu-3 cells. The effect was blocked by inhibitors of serine and cysteine proteases. Degradation of occludin was demonstrated by Western blotting and zymography indicated that diffusates contain proteolytic activity. Conclusion: Pollen peptidases directly or indirectly disrupt epithelial tight junctions, and this activity should be considered as a possible mechanism for facilitating allergen delivery across epithelia.. allergy| asthma| pollen| proteolytic enzyme| rhinitis| tight junction|dust-mite allergen| ambrosia-artemisiifolia pollen| epithelial-cells| asthma| der-p-1| purification| alpha(1)-antitrypsin| proteinases| permeability| peptidase.	NOV-2007	allergy| asthma| pollen| proteolytic enzyme| rhinitis| tight junction|dust-mite allergen| ambrosia-artemisiifolia pollen| epithelial-cells| asthma| der-p-1| purification| alpha(1)-antitrypsin| proteinases| permeability| peptidase	Runswick, S; Mitchell, T; Davies, P; Robinson, C; Garrod, DR	Pollen proteolytic enzymes degrade tight junctions		RESPIROLOGY	allergy; asthma; pollen; proteolytic enzyme; rhinitis; tight junction	DUST-MITE ALLERGEN; AMBROSIA-ARTEMISIIFOLIA POLLEN; EPITHELIAL-CELLS; ASTHMA; DER-P-1; PURIFICATION; ALPHA(1)-ANTITRYPSIN; PROTEINASES; PERMEABILITY; PEPTIDASE	Background and objective: Asthma and allergic rhinitis are significant, increasing causes of morbidity worldwide. Pollen, a major cause of seasonal rhinitis/conjunctivitis, carries proteolytic enzymes on its surface. We showed previously that peptidase allergens from house dust mites compromise epithelial barrier function by degrading the extracellular domains of the tight junction proteins, occludin and claudin, thus facilitating allergen delivery across epithelial layers. In this study, we aimed to determine whether peptidases from allergenic pollens should similarly be considered to have a role in disrupting tight junctions. Methods: Diffusates from stored pollen of Giant Ragweed, White Birch and Kentucky Blue Grass, and fresh pollen from Easter Lily were applied to confluent monolayers of Madin-Darby canine kidney (MDCK) and Calu-3 cells in serum-free medium. Immunofluorescence was performed for the tight junction proteins, occludin, claudin-1 and ZO-1. The effect of pollen diffusate on occludin was studied by Western blotting, and enzymatic activity in the diffusates was demonstrated by zymography. The ability of protease inhibitors to block the action of the diffusate on tight junctions was investigated. Results: Diffusates from all four allergenic pollens caused loss of immunofluorescence labelling for tight junction proteins on MDCK and Calu-3 cells. The effect was blocked by inhibitors of serine and cysteine proteases. Degradation of occludin was demonstrated by Western blotting and zymography indicated that diffusates contain proteolytic activity. Conclusion: Pollen peptidases directly or indirectly disrupt epithelial tight junctions, and this activity should be considered as a possible mechanism for facilitating allergen delivery across epithelia.	39	84	2007	9	10.1111/j.1440-1843.2007.01175.x	Respiratory System
Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators. BACKGROUND: Prevalence and morbidity of allergic diseases have increased over the last decades. Based on the recently recognized differences in asthma prevalence between the sexes, we have examined the effect of endogenous estrogens on a key element of the allergic response. Some lipophilic pollutants have estrogen-like activities and are termed environmental estrogens. These pollutants tend to degrade slowly in the environment and to bioaccumulate and bioconcentrate in the no chain; they also have long biological half-lives. OBJECTIVES: Our goal in this study was to identify possible pathogenic roles for environmental estrogens in the development of allergic diseases. METHODS: We screened a number of environmental estrogens for their ability to modulate the release of allergic mediators from mast cells. We incubated a human mast cell line and primary mast cell cultures derived from bone marrow of wild type and estrogen receptor alpha (ER-alpha)-deficient mice with environmental estrogens with and without estradiol or IgE and allergens. We assessed degranulation of mast cells by quantifying the release of beta-hexosaminidase. RESULTS: All of the environmental estrogens tested caused rapid, dose-related release of beta-hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17 beta-estradiol and several concentrations of environmental estrogens had additive effects on mast cell degranulation. Comparison of bone marrow mast cells from ER-alpha-sufficient and ER-alpha-deficient mice indicated that much of the effect of environmental estrogens was mediated by ER-alpha. CONCLUSIONS: Our findings suggest that estrogenic environmental pollutants might promote allergic diseases by inducing and enhancing mast cell degranulation by physiologic estrogens and exposure to allergens.. allergy| asthma| beta-hexosaminidase| environmental estrogen| estradiol| estrogen receptor alpha| ige| mast cells|pituitary-tumor cells| membrane estrogen| postnatal exposure| prolactin-release| asthma| alpha| xenoestrogens| stimulation| mechanisms| receptors.	JAN-2007	allergy| asthma| beta-hexosaminidase| environmental estrogen| estradiol| estrogen receptor alpha| ige| mast cells|pituitary-tumor cells| membrane estrogen| postnatal exposure| prolactin-release| asthma| alpha| xenoestrogens| stimulation| mechanisms| receptors	Narita, S; Goldblum, RM; Watson, CS; Brooks, EG; Estes, DM; Curran, EM; Midoro-Horiuti, T	Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators		ENVIRONMENTAL HEALTH PERSPECTIVES	allergy; asthma; beta-hexosaminidase; environmental estrogen; estradiol; estrogen receptor alpha; IgE; mast cells	PITUITARY-TUMOR CELLS; MEMBRANE ESTROGEN; POSTNATAL EXPOSURE; PROLACTIN-RELEASE; ASTHMA; ALPHA; XENOESTROGENS; STIMULATION; MECHANISMS; RECEPTORS	BACKGROUND: Prevalence and morbidity of allergic diseases have increased over the last decades. Based on the recently recognized differences in asthma prevalence between the sexes, we have examined the effect of endogenous estrogens on a key element of the allergic response. Some lipophilic pollutants have estrogen-like activities and are termed environmental estrogens. These pollutants tend to degrade slowly in the environment and to bioaccumulate and bioconcentrate in the no chain; they also have long biological half-lives. OBJECTIVES: Our goal in this study was to identify possible pathogenic roles for environmental estrogens in the development of allergic diseases. METHODS: We screened a number of environmental estrogens for their ability to modulate the release of allergic mediators from mast cells. We incubated a human mast cell line and primary mast cell cultures derived from bone marrow of wild type and estrogen receptor alpha (ER-alpha)-deficient mice with environmental estrogens with and without estradiol or IgE and allergens. We assessed degranulation of mast cells by quantifying the release of beta-hexosaminidase. RESULTS: All of the environmental estrogens tested caused rapid, dose-related release of beta-hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17 beta-estradiol and several concentrations of environmental estrogens had additive effects on mast cell degranulation. Comparison of bone marrow mast cells from ER-alpha-sufficient and ER-alpha-deficient mice indicated that much of the effect of environmental estrogens was mediated by ER-alpha. CONCLUSIONS: Our findings suggest that estrogenic environmental pollutants might promote allergic diseases by inducing and enhancing mast cell degranulation by physiologic estrogens and exposure to allergens.	29	84	2007	5	10.1289/ehp.9378	Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology
Household mouse allergen exposure and asthma morbidity in inner-city preschool children. Background: Inner-city children experience disproportionate asthma morbidity, and suspected reasons include indoor environmental exposures. Objective: To determine if mouse allergen exposure is a risk factor for asthma morbidity. Methods: Preschool children with asthma were recruited from inner-city Baltimore, MD. Skin testing was performed and blood was collected at the baseline visit for quantification of mouse allergen specific IgE. A questionnaire evaluated symptoms, medication, and health care use at baseline, 3 months, and 6 months. A trained technician collected dust samples from the child's home for analysis of Mus m 1 at baseline, 3 months, and 6 months. Outcomes were compared between mouse-sensitized, highly exposed children and all other children. Results: A total of 127 children had complete data for mouse sensitization status and bedroom settled dust mouse allergen levels at baseline. The mean age of the children was 4.4 years, 92% were African American, and 26% were sensitized to mouse. Mouse-sensitized children exposed to higher levels of Mus in 1 (> 0.5 mu g/g) had 50% more days of symptoms (incidence rate ratio [IRR], 1.5; 95% confidence interval [CI], 1.1-2.1) and 80% more days of beta-agonist use than other children (IRR, 1.8; 95% CI, 1.3-2.5). Children in the sensitized and highly exposed group were also more likely to have an unscheduled physician visit (odds ratio [OR], 3.1; 95% CI, 1.6-6.3), emergency department visit (OR, 2.1; 95% CI, 1.1-4.1), and hospitalization (OR, 36.6; 95% CI, 4.1-327.3) than other children. These associations between mouse allergen exposure and asthma symptoms and morbidity remained statistically significant after adjusting for potential confounders, including atopy and cockroach sensitization and exposure. Conclusions: In mouse-sensitized inner-city children, exposure to mouse allergen may be an important cause of asthma morbidity.. environmental tobacco-smoke| skin-test sensitivity| cockroach allergen| homes| sensitization| determinants| prevalence| symptoms| suburban| risk.	OCT-2006	environmental tobacco-smoke| skin-test sensitivity| cockroach allergen| homes| sensitization| determinants| prevalence| symptoms| suburban| risk	Matsui, EC; Eggleston, PA; Buckley, TJ; Krishnan, JA; Breysse, PN; Rand, CS; Diette, GB	Household mouse allergen exposure and asthma morbidity in inner-city preschool children		ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY		ENVIRONMENTAL TOBACCO-SMOKE; SKIN-TEST SENSITIVITY; COCKROACH ALLERGEN; HOMES; SENSITIZATION; DETERMINANTS; PREVALENCE; SYMPTOMS; SUBURBAN; RISK	Background: Inner-city children experience disproportionate asthma morbidity, and suspected reasons include indoor environmental exposures. Objective: To determine if mouse allergen exposure is a risk factor for asthma morbidity. Methods: Preschool children with asthma were recruited from inner-city Baltimore, MD. Skin testing was performed and blood was collected at the baseline visit for quantification of mouse allergen specific IgE. A questionnaire evaluated symptoms, medication, and health care use at baseline, 3 months, and 6 months. A trained technician collected dust samples from the child's home for analysis of Mus m 1 at baseline, 3 months, and 6 months. Outcomes were compared between mouse-sensitized, highly exposed children and all other children. Results: A total of 127 children had complete data for mouse sensitization status and bedroom settled dust mouse allergen levels at baseline. The mean age of the children was 4.4 years, 92% were African American, and 26% were sensitized to mouse. Mouse-sensitized children exposed to higher levels of Mus in 1 (> 0.5 mu g/g) had 50% more days of symptoms (incidence rate ratio [IRR], 1.5; 95% confidence interval [CI], 1.1-2.1) and 80% more days of beta-agonist use than other children (IRR, 1.8; 95% CI, 1.3-2.5). Children in the sensitized and highly exposed group were also more likely to have an unscheduled physician visit (odds ratio [OR], 3.1; 95% CI, 1.6-6.3), emergency department visit (OR, 2.1; 95% CI, 1.1-4.1), and hospitalization (OR, 36.6; 95% CI, 4.1-327.3) than other children. These associations between mouse allergen exposure and asthma symptoms and morbidity remained statistically significant after adjusting for potential confounders, including atopy and cockroach sensitization and exposure. Conclusions: In mouse-sensitized inner-city children, exposure to mouse allergen may be an important cause of asthma morbidity.	27	84	2006	7		Allergy; Immunology
Gender differences in murine airway responsiveness and lipopolysaccharide-induced inflammation. The roles of gender and sex hormones in lung function and disease are complex and not completely understood. The present study examined the influence. of gender on lung function and respiratory mechanics in naive mice and on acute airway inflammation and hyperresponsiveness induced by intratracheal LPS administration. Basal lung function characteristics did not differ between naive males and females, but males demonstrated significantly greater airway responsiveness than females following aerosolized methacholine challenge as evidenced by increased respiratory system resistance and elastance (p < 0.05). Following LPS administration, males developed more severe hypothermia and greater airway hyperresponsiveness than females (p < 0.05). Inflammatory indices including bronchoalveolar lavage fluid total cells, neutrophils, and TNF-alpha content were greater in males than in females 6 h following LPS administration (p < 0.05), whereas whole-lung TLR-4 protein levels did not differ among treatment groups, suggesting that differential expression of TLR-4 before or after LPS exposure did not underlie the observed inflammatory outcomes. Gonadectomy decreased airway inflammation in males but did not alter inflammation in females, whereas administration of exogenous testosterone to intact females increased their inflammatory responses to levels observed in intact males. LPS-induced airway hyperresponsiveness was also decreased in castrated males and was increased in females administered exogenous testosterone. Collectively, these data indicate that airway responsiveness in naive mice is influenced by gender, and that male mice have exaggerated airway inflammatory and functional responses to LPS compared with females. These gender differences are mediated, at least in part, by effects of androgens.. synthase-deficient mice| acute lung injury| inhaled lipopolysaccharide| testosterone| asthma| rats| estradiol| responses| estrogen| hormones.	JUL 1-2006	synthase-deficient mice| acute lung injury| inhaled lipopolysaccharide| testosterone| asthma| rats| estradiol| responses| estrogen| hormones	Card, JW; Carey, MA; Bradbury, JA; DeGraff, LM; Morgan, DL; Moorman, MP; Flake, GP; Zeldin, DC	Gender differences in murine airway responsiveness and lipopolysaccharide-induced inflammation		JOURNAL OF IMMUNOLOGY		SYNTHASE-DEFICIENT MICE; ACUTE LUNG INJURY; INHALED LIPOPOLYSACCHARIDE; TESTOSTERONE; ASTHMA; RATS; ESTRADIOL; RESPONSES; ESTROGEN; HORMONES	The roles of gender and sex hormones in lung function and disease are complex and not completely understood. The present study examined the influence. of gender on lung function and respiratory mechanics in naive mice and on acute airway inflammation and hyperresponsiveness induced by intratracheal LPS administration. Basal lung function characteristics did not differ between naive males and females, but males demonstrated significantly greater airway responsiveness than females following aerosolized methacholine challenge as evidenced by increased respiratory system resistance and elastance (p < 0.05). Following LPS administration, males developed more severe hypothermia and greater airway hyperresponsiveness than females (p < 0.05). Inflammatory indices including bronchoalveolar lavage fluid total cells, neutrophils, and TNF-alpha content were greater in males than in females 6 h following LPS administration (p < 0.05), whereas whole-lung TLR-4 protein levels did not differ among treatment groups, suggesting that differential expression of TLR-4 before or after LPS exposure did not underlie the observed inflammatory outcomes. Gonadectomy decreased airway inflammation in males but did not alter inflammation in females, whereas administration of exogenous testosterone to intact females increased their inflammatory responses to levels observed in intact males. LPS-induced airway hyperresponsiveness was also decreased in castrated males and was increased in females administered exogenous testosterone. Collectively, these data indicate that airway responsiveness in naive mice is influenced by gender, and that male mice have exaggerated airway inflammatory and functional responses to LPS compared with females. These gender differences are mediated, at least in part, by effects of androgens.	26	84	2006	10		Immunology
Nonpathogenic, environmental fungi induce activation and degranulation of human eosinophils. Eosinophils and their products are probably important in the pathophysiology of allergic diseases, such as bronchial asthma, and in host immunity to certain organisms. An association between environmental fungal exposure and asthma has been long recognized clinically. Although products of microorganisms (e.g., lipopolysaccharides) directly activate certain inflammatory cells (e.g., macrophages), the mechanism(s) that triggers eosinophil degranulation is unknown. In this study we investigated whether human eosinophils have an innate immune response to certain fungal organisms. We incubated human eosinophils with extracts from seven environmental airborne fungi (Alternaria alternata, Aspergillus versicolor, Bipolaris sorokiniana, Candida albicans, Cladosporium herbarum, Curvularia spicifera, and Penicillium notatum). Alternaria and Penicillium induced calcium-dependent exocytosis (e.g., eosinophil-derived neurotoxin release) in eosinophils from normal individuals. Alternaria also strongly induced other activation events in eosinophils, including increases in intracellular calcium concentration, cell surface expression of CD63 and CD11b, and production of IL-8. Other fungi did not induce eosinophil degranulation, and Alternaria did not induce neutrophil activation, suggesting specificity for fungal species and cell type. The Alternaria-induced eosinophil degranulation was pertussis toxin sensitive and desensitized by preincubating cells with G protein-coupled receptor agonists, platelet-activating factor, or FMLP. The eosinophil-stimulating activity in Alternaria extract was highly heat labile and had an M-r of similar to 60 kDa. Thus, eosinophils, but not neutrophils, possess G protein-dependent cellular activation machinery that directly responds to an Alternaria protein product(s). This innate response by eosinophils to certain environmental fungi may be important in host defense and in the exacerbation of inflammation in asthma and allergic diseases.. major basic-protein| blood eosinophils| potent activator| mediator release| bronchial-asthma| de-granulation| stimulation| cells| alternaria| receptors.	OCT 15-2005	major basic-protein| blood eosinophils| potent activator| mediator release| bronchial-asthma| de-granulation| stimulation| cells| alternaria| receptors	Inoue, Y; Matsuwaki, Y; Shin, SH; Ponikau, JU; Kita, H	Nonpathogenic, environmental fungi induce activation and degranulation of human eosinophils		JOURNAL OF IMMUNOLOGY		MAJOR BASIC-PROTEIN; BLOOD EOSINOPHILS; POTENT ACTIVATOR; MEDIATOR RELEASE; BRONCHIAL-ASTHMA; DE-GRANULATION; STIMULATION; CELLS; ALTERNARIA; RECEPTORS	Eosinophils and their products are probably important in the pathophysiology of allergic diseases, such as bronchial asthma, and in host immunity to certain organisms. An association between environmental fungal exposure and asthma has been long recognized clinically. Although products of microorganisms (e.g., lipopolysaccharides) directly activate certain inflammatory cells (e.g., macrophages), the mechanism(s) that triggers eosinophil degranulation is unknown. In this study we investigated whether human eosinophils have an innate immune response to certain fungal organisms. We incubated human eosinophils with extracts from seven environmental airborne fungi (Alternaria alternata, Aspergillus versicolor, Bipolaris sorokiniana, Candida albicans, Cladosporium herbarum, Curvularia spicifera, and Penicillium notatum). Alternaria and Penicillium induced calcium-dependent exocytosis (e.g., eosinophil-derived neurotoxin release) in eosinophils from normal individuals. Alternaria also strongly induced other activation events in eosinophils, including increases in intracellular calcium concentration, cell surface expression of CD63 and CD11b, and production of IL-8. Other fungi did not induce eosinophil degranulation, and Alternaria did not induce neutrophil activation, suggesting specificity for fungal species and cell type. The Alternaria-induced eosinophil degranulation was pertussis toxin sensitive and desensitized by preincubating cells with G protein-coupled receptor agonists, platelet-activating factor, or FMLP. The eosinophil-stimulating activity in Alternaria extract was highly heat labile and had an M-r of similar to 60 kDa. Thus, eosinophils, but not neutrophils, possess G protein-dependent cellular activation machinery that directly responds to an Alternaria protein product(s). This innate response by eosinophils to certain environmental fungi may be important in host defense and in the exacerbation of inflammation in asthma and allergic diseases.	58	84	2005	9		Immunology
Mild and moderate-to-severe COPD in nonsmokers - Distinct demographic profiles. Study objective: To investigate the risk of COPD among nonsmokers. Design: Case-control study, logistic regression analysis. Setting: Third National Health and Nutrition Examination Survey, from 1988 to 1994. Participants: Community, residents 18 to 80 years of age, of white, black, or Mexican-American ethnicity. Nonsmokers included never-smokers and former smokers with a < 5 pack-year smoking history, who had never smoked cigars or pipes. Measurements: COPD (FEV1/FVC < 70%) was classified as mild (FEV1 >= 80% predicted) or moderate to severe (FEV1 23 to 79% predicted). Results: Among 13,995 examinees, 51.3 +/- 0.4% were female, mean age was 42.2 +/- 0.4 cars, 48.7 +/- 0.9% were nonsmokers, 8.8 +/- 0.3% had mild COPD, and 4.1 +/- 0.3% had moderate-to-severe COPD [+/- SE]. One fourth of mild and moderate-to-severe cases were nonsmokers. Among 7,526 nonsmokers, 4.7 +/- 0.3% had mild COPD (n = 403; age, 60.9 +/- 1.3 years) and were mostly, female (82.5%), while 1.9 +/- 0.3% had moderate-to-severe COPD (n = 92, age 39.3 +/- 1.3) and were mostly male (88.1%). Few nonsmokers with COPD (12.1 +/- 2.4%) had a previous diagnosis of chronic bronchitis or emphysema. Among nonsmokers, physician-diagnosed asthma increased the risk of mild and especially of moderate-to-severe COPD. Independently of asthma, risk of mild COPD in nonsmokers increased with age (doubling every, 12 years), before age 60 was lower among men than women, and was inversely associated with current exposure to tobacco smoke at home and at work. In contrast, the risk of moderate-to-severe COPD in nonsmokers was markedly associated with male gender, peaked in middle age, and was inversely associated with nonwhite ethnicity. COPD risks did not vary by minimal smoking history, longest-held occupation, urban residence, income, allergies, thyroid disease, or Helicobacter pylori antibody. Conclusions: Among nonsmokers, mild and moderate-to-severe COPD are associated with asthma but otherwise have distinct demographic profiles, suggesting that moderate-to-severe disease is not a mere progression of mild COPD.. asthma| copd| epidemiology| nonsmoker|obstructive pulmonary-disease| nutrition examination| national-health| united-states| lung-disease| population| asthma| mortality| sample| nhanes.	SEP-2005	asthma| copd| epidemiology| nonsmoker|obstructive pulmonary-disease| nutrition examination| national-health| united-states| lung-disease| population| asthma| mortality| sample| nhanes	Behrendt, CE	Mild and moderate-to-severe COPD in nonsmokers - Distinct demographic profiles		CHEST	asthma; COPD; epidemiology; nonsmoker	OBSTRUCTIVE PULMONARY-DISEASE; NUTRITION EXAMINATION; NATIONAL-HEALTH; UNITED-STATES; LUNG-DISEASE; POPULATION; ASTHMA; MORTALITY; SAMPLE; NHANES	Study objective: To investigate the risk of COPD among nonsmokers. Design: Case-control study, logistic regression analysis. Setting: Third National Health and Nutrition Examination Survey, from 1988 to 1994. Participants: Community, residents 18 to 80 years of age, of white, black, or Mexican-American ethnicity. Nonsmokers included never-smokers and former smokers with a < 5 pack-year smoking history, who had never smoked cigars or pipes. Measurements: COPD (FEV1/FVC < 70%) was classified as mild (FEV1 >= 80% predicted) or moderate to severe (FEV1 23 to 79% predicted). Results: Among 13,995 examinees, 51.3 +/- 0.4% were female, mean age was 42.2 +/- 0.4 cars, 48.7 +/- 0.9% were nonsmokers, 8.8 +/- 0.3% had mild COPD, and 4.1 +/- 0.3% had moderate-to-severe COPD [+/- SE]. One fourth of mild and moderate-to-severe cases were nonsmokers. Among 7,526 nonsmokers, 4.7 +/- 0.3% had mild COPD (n = 403; age, 60.9 +/- 1.3 years) and were mostly, female (82.5%), while 1.9 +/- 0.3% had moderate-to-severe COPD (n = 92, age 39.3 +/- 1.3) and were mostly male (88.1%). Few nonsmokers with COPD (12.1 +/- 2.4%) had a previous diagnosis of chronic bronchitis or emphysema. Among nonsmokers, physician-diagnosed asthma increased the risk of mild and especially of moderate-to-severe COPD. Independently of asthma, risk of mild COPD in nonsmokers increased with age (doubling every, 12 years), before age 60 was lower among men than women, and was inversely associated with current exposure to tobacco smoke at home and at work. In contrast, the risk of moderate-to-severe COPD in nonsmokers was markedly associated with male gender, peaked in middle age, and was inversely associated with nonwhite ethnicity. COPD risks did not vary by minimal smoking history, longest-held occupation, urban residence, income, allergies, thyroid disease, or Helicobacter pylori antibody. Conclusions: Among nonsmokers, mild and moderate-to-severe COPD are associated with asthma but otherwise have distinct demographic profiles, suggesting that moderate-to-severe disease is not a mere progression of mild COPD.	23	84	2005	6	10.1378/chest.128.3.1239	General & Internal Medicine; Respiratory System
"Gene-environment interaction effects on the development of immune responses in the 1st year of life. Asthma is a common disease that results from both genetic and environmental risk factors. Children attending day care in the 1st year of life have lower risks for developing asthma, although the mechanism for this ""day care"" effect is largely unknown. We investigated the interactions between day care exposure in the 1st 6 mo of life and genotypes for 72 polymorphisms at 45 candidate loci and their effects on cytokine response profiles and on the development of atopic phenotypes in the 1st year of life in the Childhood Onset of Asthma ( COAST) cohort of children. Six interactions ( at four polymorphisms in three loci) with ""day care"" that had an effect on early-life immune phenotypes were significant at P < .001. The estimated false-discovery rate was 33%, indicating that an estimated four P values correspond to true associations. Moreover, the "" day care"" effect at some loci was accounted for by the increased number of viral infections among COAST children attending day care, whereas interactions at other loci were independent of the number of viral infections, indicating the presence of additional risk factors associated with day care environment. This study identified significant gene-environment interactions influencing the early patterning of the immune system and the subsequent development of asthma and highlights the importance of considering environmental risk factors in genetic analyses.. interferon-gamma production| day-care attendance| blood mononuclear-cells| asthma susceptibility gene| hygiene hypothesis| high-risk| allergic diseases| atopic disease| age-children| ifn-gamma."	APR-2005	interferon-gamma production| day-care attendance| blood mononuclear-cells| asthma susceptibility gene| hygiene hypothesis| high-risk| allergic diseases| atopic disease| age-children| ifn-gamma	Hoffjan, S; Nicolae, D; Ostrovnaya, I; Roberg, K; Evans, M; Mirel, DB; Steiner, L; Walker, K; Shult, P; Gangnon, RE; Gern, JE; Martinez, FD; Lemanske, RF; Ober, C	Gene-environment interaction effects on the development of immune responses in the 1st year of life		AMERICAN JOURNAL OF HUMAN GENETICS		INTERFERON-GAMMA PRODUCTION; DAY-CARE ATTENDANCE; BLOOD MONONUCLEAR-CELLS; ASTHMA SUSCEPTIBILITY GENE; HYGIENE HYPOTHESIS; HIGH-RISK; ALLERGIC DISEASES; ATOPIC DISEASE; AGE-CHILDREN; IFN-GAMMA	"Asthma is a common disease that results from both genetic and environmental risk factors. Children attending day care in the 1st year of life have lower risks for developing asthma, although the mechanism for this ""day care"" effect is largely unknown. We investigated the interactions between day care exposure in the 1st 6 mo of life and genotypes for 72 polymorphisms at 45 candidate loci and their effects on cytokine response profiles and on the development of atopic phenotypes in the 1st year of life in the Childhood Onset of Asthma ( COAST) cohort of children. Six interactions ( at four polymorphisms in three loci) with ""day care"" that had an effect on early-life immune phenotypes were significant at P < .001. The estimated false-discovery rate was 33%, indicating that an estimated four P values correspond to true associations. Moreover, the "" day care"" effect at some loci was accounted for by the increased number of viral infections among COAST children attending day care, whereas interactions at other loci were independent of the number of viral infections, indicating the presence of additional risk factors associated with day care environment. This study identified significant gene-environment interactions influencing the early patterning of the immune system and the subsequent development of asthma and highlights the importance of considering environmental risk factors in genetic analyses."	57	84	2005	9	10.1086/429418	Genetics & Heredity
A comparison of indoor air pollutants in Japan and Sweden: formaldehyde, nitrogen dioxide, and chlorinated volatile organic compounds. Indoor and outdoor concentrations of formaldehyde (HCHO), nitrogen dioxide (NO2), and selected chlorinated volatile organic compounds (chlorinated VOC) were measured in 37 urban dwellings in Nagoya, Japan, and 27 urban dwellings in Uppsala, Sweden, using the same sampling procedures and analytical methods. Indoor as well as outdoor air concentrations of HCHO, NO2, and chlorinated VOC were significantly higher in Nagoya than in Uppsala (P<0.01), with the exception of tetrachlorocarbon in outdoor air. In Nagoya, HCHO and NO2 concentrations were significantly higher in modern concrete houses than in wooden houses and higher in newer (less than 10 years) than in older dwellings (P < 0.01), possibly due to less natural ventilation and more emission sources in modern buildings. Dwellings heated with unvented combustion sources had significantly higher indoor concentrations of NO2\ than those with clean heating (P<0.05). Moreover, dwellings with moth repellents containing p-dichlorobenzene had significantly higher indoor concentrations of p-dichlorobenzene (P < 0.01). In conclusion, there appear to be differences between Nagoya and Uppsala with respect to both indoor and outdoor pollution levels of the measured pollutants. More indoor pollution sources could be identified in Nagoya than in Uppsala, including construction and interior materials emitting VOC, use of unvented combustion space heaters, and moth repellents containing p-dichlorobenzene. (C) 2003 Elsevier Inc. All rights reserved.. formaldehyde| nitrogen dioxide| chlorinated voc| indoor air pollution| international comparison|sick building syndrome| exposure| prevalence| symptoms| emission| products| asthma| areas| team.	JAN-2004	formaldehyde| nitrogen dioxide| chlorinated voc| indoor air pollution| international comparison|sick building syndrome| exposure| prevalence| symptoms| emission| products| asthma| areas| team	Sakai, K; Norback, D; Mi, YH; Shibata, E; Kamijima, M; Yamada, T; Takeuchi, Y	A comparison of indoor air pollutants in Japan and Sweden: formaldehyde, nitrogen dioxide, and chlorinated volatile organic compounds		ENVIRONMENTAL RESEARCH	formaldehyde; nitrogen dioxide; chlorinated VOC; indoor air pollution; international comparison	SICK BUILDING SYNDROME; EXPOSURE; PREVALENCE; SYMPTOMS; EMISSION; PRODUCTS; ASTHMA; AREAS; TEAM	Indoor and outdoor concentrations of formaldehyde (HCHO), nitrogen dioxide (NO2), and selected chlorinated volatile organic compounds (chlorinated VOC) were measured in 37 urban dwellings in Nagoya, Japan, and 27 urban dwellings in Uppsala, Sweden, using the same sampling procedures and analytical methods. Indoor as well as outdoor air concentrations of HCHO, NO2, and chlorinated VOC were significantly higher in Nagoya than in Uppsala (P<0.01), with the exception of tetrachlorocarbon in outdoor air. In Nagoya, HCHO and NO2 concentrations were significantly higher in modern concrete houses than in wooden houses and higher in newer (less than 10 years) than in older dwellings (P < 0.01), possibly due to less natural ventilation and more emission sources in modern buildings. Dwellings heated with unvented combustion sources had significantly higher indoor concentrations of NO2\ than those with clean heating (P<0.05). Moreover, dwellings with moth repellents containing p-dichlorobenzene had significantly higher indoor concentrations of p-dichlorobenzene (P < 0.01). In conclusion, there appear to be differences between Nagoya and Uppsala with respect to both indoor and outdoor pollution levels of the measured pollutants. More indoor pollution sources could be identified in Nagoya than in Uppsala, including construction and interior materials emitting VOC, use of unvented combustion space heaters, and moth repellents containing p-dichlorobenzene. (C) 2003 Elsevier Inc. All rights reserved.	39	84	2004	11	10.1016/S0013-9351(03)00140-3	Environmental Sciences & Ecology; Public, Environmental & Occupational Health
Environmental tobacco smoke and adult-onset asthma: A population-based incident case-control study. Objectives. The authors assessed the effects of environmental tobacco smoke (ETS) on the development of asthma in adults. Methods. In the Pirkanmaa district of South Finland, all 21- to 63 year-old adults with new cases of asthma diagnosed during a 2.5-year period (n=521 case patients. out of 441000 inhabitants) and a random sample of control subjects from the source population (932 control subjects) participated in a population-based incident case-control study. Results. Risk of asthma was related to workplace ETS exposure (adjusted odds ratio [OR] = 2.16; 95% confidence interval [CI] = 1.26, 3.72) and home exposure (OR = 4.77; 95% CI = 1.29, 17.7) in the past year. Cumulative ETS exposure over a lifetime at work and at home increased the risk. Conclusions. This study indicates for the first time that both cumulative lifetime and recent ETS exposures increase the risk of adult-onset asthma.. respiratory symptoms| passive smoking| exposure| nonsmoking.	DEC-2003	respiratory symptoms| passive smoking| exposure| nonsmoking	Jaakkola, MS; Piipari, R; Jaakkola, N; Jaakkola, JJK	Environmental tobacco smoke and adult-onset asthma: A population-based incident case-control study		AMERICAN JOURNAL OF PUBLIC HEALTH		RESPIRATORY SYMPTOMS; PASSIVE SMOKING; EXPOSURE; NONSMOKING	Objectives. The authors assessed the effects of environmental tobacco smoke (ETS) on the development of asthma in adults. Methods. In the Pirkanmaa district of South Finland, all 21- to 63 year-old adults with new cases of asthma diagnosed during a 2.5-year period (n=521 case patients. out of 441000 inhabitants) and a random sample of control subjects from the source population (932 control subjects) participated in a population-based incident case-control study. Results. Risk of asthma was related to workplace ETS exposure (adjusted odds ratio [OR] = 2.16; 95% confidence interval [CI] = 1.26, 3.72) and home exposure (OR = 4.77; 95% CI = 1.29, 17.7) in the past year. Cumulative ETS exposure over a lifetime at work and at home increased the risk. Conclusions. This study indicates for the first time that both cumulative lifetime and recent ETS exposures increase the risk of adult-onset asthma.	22	84	2003	6	10.2105/AJPH.93.12.2055	Public, Environmental & Occupational Health
A comparison of the clinical characteristics of children and adults with severe asthma. Objectives: This study sought to better define the clinical characteristics of severe asthma in both children and adults, and to evaluate the effect of asthma duration on multiple parameters of disease severity. Design: Retrospective analysis of prospectively collected data on 275 patients (125 children) with severe asthma who were admitted to a tertiary asthma referral center. Methods: Demographics, lung function (ie, spirometry and body box plethysmography), glueocorticoid (GC) pharmacokinetic studies, and lymphocyte stimulation assays were performed on all patients. Results: Children were as likely to require therapy with high-dose inhaled GCs and long-term therapy with oral GCs, and to have had a prior intubation, yet they had significantly less airflow limitation (mean [+/-SEM] (.) FEV1, 74.0 +/- 2.1% predicted vs 57.1 +/- 1.8% predicted, respectively; p < 0.0001), less resistance to airflow (mean airway resistance, 140.3 +/- 8.5% predicted vs 311 +/- 18% predicted, respectively; p < 0.0001), and larger lung volumes (mean total lung capacity, 116.4 1.6% predicted vs 105.3 +/- 1.8% predicted, respectively; p < 0.0001) compared to adults. Children were more likely to be male and to display greater responsiveness to GCs in vitro. Lung function impairment was associated with asthma duration in children and in adults with onset of asthma in childhood, while there was no relationship between disease severity and asthma duration among those with adult-onset asthma. Despite significant differences in disease duration, patients with adult-onset asthma had equally compromised lung function compared to adults with long-standing asthma. Conclusions: Children with severe asthma tended to be male, to have less severe airflow obstruction, and to display greater responsiveness to GCs in vitro compared to adults. Symptoms and episodic acute declines in lung function may precede chronic airflow limitation in this group of children. As such, it may be more relevant to follow the deterioration in lung function over time in children. Finally, disease severity in children and adults whose onset of asthma occurred in childhood was related to disease duration, but not in patients with onset of asthma in adulthood.. adult-onset asthma| childbood-onset asthma| glucocorticoids| national heart, lung, and blood institute| guidelines| severe asthma|air-flow obstruction| childhood-onset| lung-function| population| sample.	OCT-2003	adult-onset asthma| childbood-onset asthma| glucocorticoids| national heart, lung, and blood institute| guidelines| severe asthma|air-flow obstruction| childhood-onset| lung-function| population| sample	Jenkins, HA; Cherniack, R; Szefler, SJ; Covar, R; Gelfand, EW; Spahn, JD	A comparison of the clinical characteristics of children and adults with severe asthma		CHEST	adult-onset asthma; childbood-onset asthma; glucocorticoids; National Heart, Lung, and Blood Institute; guidelines; severe asthma	AIR-FLOW OBSTRUCTION; CHILDHOOD-ONSET; LUNG-FUNCTION; POPULATION; SAMPLE	Objectives: This study sought to better define the clinical characteristics of severe asthma in both children and adults, and to evaluate the effect of asthma duration on multiple parameters of disease severity. Design: Retrospective analysis of prospectively collected data on 275 patients (125 children) with severe asthma who were admitted to a tertiary asthma referral center. Methods: Demographics, lung function (ie, spirometry and body box plethysmography), glueocorticoid (GC) pharmacokinetic studies, and lymphocyte stimulation assays were performed on all patients. Results: Children were as likely to require therapy with high-dose inhaled GCs and long-term therapy with oral GCs, and to have had a prior intubation, yet they had significantly less airflow limitation (mean [+/-SEM] (.) FEV1, 74.0 +/- 2.1% predicted vs 57.1 +/- 1.8% predicted, respectively; p < 0.0001), less resistance to airflow (mean airway resistance, 140.3 +/- 8.5% predicted vs 311 +/- 18% predicted, respectively; p < 0.0001), and larger lung volumes (mean total lung capacity, 116.4 1.6% predicted vs 105.3 +/- 1.8% predicted, respectively; p < 0.0001) compared to adults. Children were more likely to be male and to display greater responsiveness to GCs in vitro. Lung function impairment was associated with asthma duration in children and in adults with onset of asthma in childhood, while there was no relationship between disease severity and asthma duration among those with adult-onset asthma. Despite significant differences in disease duration, patients with adult-onset asthma had equally compromised lung function compared to adults with long-standing asthma. Conclusions: Children with severe asthma tended to be male, to have less severe airflow obstruction, and to display greater responsiveness to GCs in vitro compared to adults. Symptoms and episodic acute declines in lung function may precede chronic airflow limitation in this group of children. As such, it may be more relevant to follow the deterioration in lung function over time in children. Finally, disease severity in children and adults whose onset of asthma occurred in childhood was related to disease duration, but not in patients with onset of asthma in adulthood.	18	84	2003	7	10.1378/chest.124.4.1318	General & Internal Medicine; Respiratory System
