Background The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses. Objective We sought to investigate the natural IgE and IgG responses ...toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads. Methods A cross-sectional analysis was conducted in 340 adults of the EGEA (Epidemiological study of the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) (170 with and 170 without asthma) cohort. IgE and IgG responses to 47 inhalant and food allergen components were analyzed in sera using allergen microarray and compared between 5 French regions according to the route of allergen exposure (inhaled vs food allergens). Results Overall 48.8% of the population had allergen-specific IgE levels of 0.3 ISAC standardized units (ISU) or more to at least 1 of the 47 allergens with no significant differences across the regions. For ubiquitous respiratory allergens (ie, grass, olive/ash pollen, house dust mites), specific IgE did not show marked differences between regions and specific IgG (≥0.5 ISU) was present in most subjects everywhere. For regionally occurring pollen allergens (ragweed, birch, cypress), IgE sensitization was significantly associated with regional pollen exposure. For airborne allergens cross-reacting with food allergens, frequent IgG recognition was observed even in regions with low allergen prevalence (Bet v 1) or for allergens less frequently recognized by IgE (profilins). Conclusions The variability in allergen-specific IgE and IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergen. Allergen contact by the oral route might preferentially induce IgG responses.
Background Whether small-airway obstruction contributes to the long-term evolution of asthma remains unknown. Objectives Our aim was to assess whether the level of forced midexpiratory flow between ...25% and 75% of forced vital capacity (FEF25-75 ) was associated with the persistence of current asthma over 20 years and the subsequent risk for uncontrolled asthma independently of FEV1. Methods We studied 337 participants (142 children and 225 adults) with current asthma (asthma attacks or treatment in the past 12 months) recruited to the Epidemiological Study on the Genetics and Environment of Asthma (EGEA1) and followed up at the 12- and 20-year surveys. Persistent current asthma was defined by current asthma reported at each survey. A lung function test and a methacholine challenge test were performed at EGEA1 and EGEA2. Adjusted odds ratios (ORs) were estimated for FEF25-75 decreased by 10% of predicted value. Results A reduced level of FEF25-75 at EGEA1 increased the risk of long-term asthma persistence (adjusted OR, 1.14; 95% CI, 1.00-1.29). In children the association remained significant after further adjustment for FEV1 and in participants with FEV1 of greater than 80% of predicted value. A reduced FEF25-75 level at EGEA1 was significantly associated with more severe bronchial hyperresponsiveness ( P < .0001) and with current asthma a decade later, with an association that tended to be stronger in those with (adjusted OR, 1.44; 95% CI, 1.14-1.81) compared with those without (adjusted OR, 1.21; 95% CI, 1.05-1.41) asthma exacerbation. Conclusion Our analysis is the first to suggest that small-airway obstruction, as assessed based on FEF25-75 , might contribute to the long-term persistence of asthma and the subsequent risk for poor asthma outcomes independently from effects of the large airways.
...chronic exposures, such as smoking, occupational exposure to silica, and firefighting, are associated with decreased serum CC-16 levels.2,3 Clinical studies have shown decreased serum levels of ...CC-16 in asthmatic subjects4,5 and in patients with chronic obstructive pulmonary disease (COPD).6 A positive association between serum CC-16 levels and FEV1 was recently observed in a large clinical study on patients with COPD.7 However, there is a lack of epidemiological studies addressing the relation of serum CC-16 levels with asthma and lung function in the general population. A positive association between serum CC-16 levels and lung function has been reported in clinical studies7 and in occupationally exposed subjects.\n38-1.30) <.001 Table I Unadjusted and adjusted estimates (95% CI and P) for the association between a 1-SD increase in serum CC-16 level (g/L) and asthma, spirometric patterns, and lung function BMI, Body mass index; GOLD, Global Initiative for Obstructive Lung Disease; LLN, lower limit of normal; OR, odds ratio; RRR, relative risk ratio.
No data are available regarding the utility of fractional exhaled nitric oxide (FeNO) level in guiding therapy in smoking asthmatic patients. Identification of the effect of smoking in a large sample ...is needed.
To study the association between smoking and FeNO level according to current asthma and atopy status in adults from the French EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy).
Levels of FeNO were measured at 50 mL/s in 654 adults (268 asthmatic participants). Active smoking and environmental tobacco smoke (ETS) exposure at home, at work, and during leisure activities were recorded. Participants were categorized as having no exposure to ETS, mild exposure (ETS <2 h/d), and noticeable exposure (ETS > or = 2 h/d). Multivariate analyses were performed, with adjustment for age, sex, height, and center.
Mean adjusted FeNO values increased with asthma (15.1 vs 19.5 ppb), atopy (14.2 vs 18.9 ppb), and eosinophilia (15.8 vs 24.8 ppb) (P < .001 for all). Mean FeNO levels decreased with smoking (18.4, 17.5, and 14.5 ppb in nonsmokers, ex-smokers, and current smokers, respectively; P for trend = .001). The association with smoking was observed in nonasthmatic and asthmatic participants, especially in atopic asthmatic participants. Multivariate analyses showed that ETS exposure of at least 2 h/d and active smoking were negatively and significantly associated with FeNO levels independent of age, sex, height, and center in nonasthmatic participants (mean SE, -0.13 0.06, P = .03 and -0.10 0.03, P < .001) and in asthmatic participants (mean SE, -0.18 0.07, P = .01 and -0.14 0.04, P = .02).
Active and passive smoking decreased FeNO levels in adults. Careful consideration of asthma, atopy, and active and passive smoking are needed to interpret FeNO values.
Background Integrin β3 ( ITGB3 ) and Toll-like receptor 2 ( TLR2 ) are candidate genes for asthma and sensitization to mold allergens. Integrin β3 forms a complex with TLR2, and this biological ...interaction is required for the response of monocytes to TLR2 agonists such as fungal glucan. Objective To study whether genetic interaction between single nucleotide polymorphisms (SNPs) in genes encoding the TLR2-ITGB3 complex enhances susceptibility to mold sensitization. Methods Association analysis was conducted in 1243 adults (524 with asthma) who participated in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma. Allergic sensitization to mold allergens was determined by skin prick testing. Association of mold sensitization with 14 ITGB3 SNPs was tested under an additive genetic model. Interaction between ITGB3 SNPs and TLR2 /+596, which was previously shown to be associated with asthma, was studied. Results A positive skin prick test to mold was found in 115 subjects with asthma (22.0%) and in 61 subjects without asthma (8.5%). The ITGB3 rs2056131 A allele was associated with mold sensitization in subjects with asthma with an odds ratio (95% CI) of 0.60 (0.43-0.83; P = .001). Ten other ITGB3 SNPs were significantly associated with mold sensitization in TLR2 /+596TT subjects with asthma ( P = .03-.002), whereas much weaker associations were found in carriers of the TLR2 /+596 C allele ( P = .60-.04). Interaction between TLR2 /+596 and these ITGB3 SNPs was statistically significant ( P interaction = .05-.001). Conclusion TLR2/+596 genotype may influence the association between ITGB3 SNPs and mold sensitization in adults with asthma.
Background Delineating asthma subphenotypes is of interest to understand the cause of the disease. Few studies have addressed the interrelationships of quantitative asthma-related traits. Objective ...We sought to study the interrelationships of allergy markers and FEV1 in relation to asthma and sex in children and adults. Methods Total IgE levels, skin prick test (SPT) positivity, eosinophil counts, and FEV1 were assessed in 299 asthmatic cases (children and adults) recruited in chest clinics and 309 nonasthmatic population-based control subjects in the French Epidemiological Study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy. Results Allergy parameters were significantly higher in asthmatic cases than in control subjects for children and adults and for both sexes. Sex and age modified the pattern of concordance of high IgE levels, SPT positivity, and eosinophilia among asthmatic cases, with the greatest overlap in male children (64%) and the lowest in male adults (18%). Patterns of change over the lifespan of IgE levels, eosinophil counts, and FEV1 /height2 varied, with the acceleration of FEV1 decrease being particularly evident in asthmatic adults. In adult cases and control subjects, SPT positivity (particularly to indoor allergens) was significantly related to IgE levels but not to eosinophil counts. The association of eosinophil counts with IgE levels was evident only in children. Environmental factors (smoking, pets, and country living) did not alter the patterns observed. Conclusions Each allergy-related phenotype showed a distinct relation with asthma, with the role for eosinophils being different than that for IgE levels and SPT responses. Clinical implications Taking age and sex into account is essential for understanding the interrelationships of the various allergy-related phenotypes to asthma status.
Background Genome-wide association studies have identified determinants of chronic obstructive pulmonary disease, asthma, and lung function level; however, none have addressed decline in lung ...function. Objective We conducted the first genome-wide association study on the age-related decrease in FEV1 and its ratio to forced vital capacity (FVC) stratified a priori by asthma status. Methods Discovery cohorts included adults of European ancestry (1,441 asthmatic and 2,677 nonasthmatic participants: the Epidemiological Study on the Genetics and Environment of Asthma, the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults, and the European Community Respiratory Health Survey). The associations of FEV1 and FEV1 /FVC ratio decrease with 2.5 million single nucleotide polymorphisms (SNPs) were estimated. Thirty loci were followed up by in silico replication (1,160 asthmatic and 10,858 nonasthmatic participants: Atherosclerosis Risk in Communities, the Framingham Heart Study, the British 1958 Birth Cohort, and the Dutch Asthma Study). Results Main signals identified differed between asthmatic and nonasthmatic participants. None of the SNPs reached genome-wide significance. The association between the height-related gene DLEU7 and FEV1 decrease suggested for nonasthmatic participants in the discovery phase was replicated (discovery, P = 4.8 × 10−6 ; replication, P = .03), and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3 , which is associated with FEV1 /FVC ratio decrease in asthmatic participants ( P = 5.3 × 10−8 ), did not replicate. SNPs previously associated with cross-sectional lung function were not prominently associated with decline. Conclusions Genetic heterogeneity of lung function might be extensive. Our results suggest that genetic determinants of longitudinal and cross-sectional lung function differ and vary by asthma status.
Phenotypic determinants of uncontrolled asthma Siroux, Valérie, PhD; Boudier, Anne, MSc; Bousquet, Jean, MD ...
Journal of allergy and clinical immunology,
10/2009, Letnik:
124, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background Although uncontrolled asthma remains frequent, determinants of asthma control are poorly studied. Objectives The aim was to estimate the distribution and the phenotypic characteristics of ...asthma control in 2 groups of subjects defined by the use of inhaled corticosteroids (ICS) in the past 12 months, in the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). Methods Five hundred one adult current patients with asthma who participated in the follow-up of the EGEA study were included. Asthma control was assessed from survey questions reflecting asthma control, as defined in the 2006 Global Initiative for Asthma guidelines. The factors analyzed were age, sex, educational level, body mass index, active and passive smoking, sensitization to aeroallergens, total IgE, rhinitis, chronic cough/phlegm, and age at asthma onset. Analyses were stratified according to ICS use. Results Uncontrolled asthma was more frequent in ICS users (27.6%, 35.0%, and 37.4% with controlled, partly-controlled, and uncontrolled asthma respectively) compared with non-ICS users (60.0%, 23.9%, and 16.1%, respectively). In ICS users, chronic cough or phlegm and female sex were independently and significantly related to uncontrolled asthma. In non-ICS users, high total IgE and sensitization to molds were associated with uncontrolled asthma. Smoking and rhinitis were not associated with asthma control. Conclusion Optimal asthma control remained unachieved in the majority of patients with asthma in this study. Factors associated with uncontrolled asthma were different in ICS users (chronic cough/phlegm, female sex) and non-ICS users (high total IgE and sensitization to molds).
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