Search

Background: Longitudinal studies assessing the association of profiles of allergen‐specific IgE (sIgE) sensitization to a large range of allergen molecules and respiratory health are rare. We aimed to assess trajectories of molecular sIgE sensitization profiles from childhood to adulthood and their associations with respiratory health. Methods: IgE reactivity to microarrayed allergen molecules were measured in childhood (EGEA1) and 12 years later in adult life (EGEA2) among 291 EGEA participants (152 with asthma). At each time point, sIgE sensitization profiles were identified by latent class analysis (LCA) by considering IgE‐reactivity to the 38 most prevalent respiratory allergens. The LCA‐defined profiles were then studied in association with respiratory health. Results: At baseline, the mean (min‐max) age of the population was 11 (4.5–16) years. The LCA identified four sIgE sensitization profiles which were very similar at both time points (% at EGEA1 and EGEA2); A: "no/few allergen(s)" (48%, 39%), B: "pollen/animal allergens" (18%, 21%), C: "most prevalent house dust mite allergens" (22%, 27%) and D: "many allergens" (12%, 13%). Overall, 73% of the participants remained in the same profile from childhood to adulthood. The profiles were associated with asthma and rhinitis phenotypes. Participants of profiles C and D had lower FEV1% and FEF25‐75% as compared to profile A. Similar patterns of associations were observed for participants with asthma. There was no association with change in lung function. Conclusion: Using high‐resolution sIgE longitudinal data, the LCA identified four molecular sensitization profiles, mainly stable from childhood to adulthood, that were associated with respiratory health. [ABSTRACT FROM AUTHOR]

Background: The classification of rhinitis in adults is missing in epidemiological studies. Objective: To identify phenotypes of adult rhinitis using an unsupervised approach (data-driven) compared with a classical hypothesis-driven approach. Methods: 983 adults of the French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) were studied. Self-reported symptoms related to rhinitis such as nasal symptoms, hay fever, sinusitis, conjunctivitis, and sensitivities to different triggers (dust, animals, hay/flowers, cold air…) were used. Allergic sensitization was defined by at least one positive skin prick test to 12 aeroallergens. Mixture model was used to cluster participants, independently in those without (Asthma-, n = 582) and with asthma (Asthma+, n = 401). Results: Three clusters were identified in both groups: 1) Cluster A (55% in Asthma-, and 22% in Asthma+) mainly characterized by the absence of nasal symptoms, 2) Cluster B (23% in Asthma-, 36% in Asthma+) mainly characterized by nasal symptoms all over the year, sinusitis and a low prevalence of positive skin prick tests, and 3) Cluster C (22% in Asthma-, 42% in Asthma+) mainly characterized by a peak of nasal symptoms during spring, a high prevalence of positive skin prick tests and a high report of hay fever, allergic rhinitis and conjunctivitis. The highest rate of polysensitization (80%) was found in participants with comorbid asthma and allergic rhinitis. Conclusion: This cluster analysis highlighted three clusters of rhinitis with similar characteristics than those known by clinicians but differing according to allergic sensitization, and this whatever the asthma status. These clusters could be easily rebuilt using a small number of variables. [ABSTRACT FROM AUTHOR]

Background: The associations between exposure to air pollution and asthma control are not well known. The objective of this study was to assess the association between long-term exposure to NO2, O3 and PM10 and asthma control in the follow-up of the Epidemiological study on the Genetics and Environment of Asthma(EGEA2) (2003-2007).Methods: Modelled outdoor NO2, O3 and PM10estimates were linked to each residential address using the 4 km grid air pollutant surface developed by the French Institute of Environment in 2004. Asthma control was assessed in 481 subjects with current asthma using a multidimensional approach following the 2006-2009Global Initiative for Asthma guidelines. Multinomial and ordinal logistic regressions were conducted adjusted for sex, age, body mass index, education, smoking and use of inhaled corticosteroids. The association between air pollution and the three domains of asthma control(symptoms, exacerbations and lung function) was assessed. ORs are reported per IQR.Results: Median concentrations (in micrograms per cubic metre) were 32 (IQR 25-38) for NO2 (n=465), 46(41-52) for O3 and 21 (18-21) for PM10 (n=481). In total, 44%, 29% and 27% had controlled, partly controlled and uncontrolled asthma, respectively. The ordinal ORs for O3 and PM10 with asthma control were1.69 (95% CI 1.22 to 2.34) and 1.35 (95% CI 1.13 to1.64), respectively. When including both pollutants in the same model, both associations persisted. Associations were not modified by sex, smoking status, use of inhaledcorticosteroids, atopy, season of examination or body mass index. Both pollutants were associated with each of the three main domains of control.Conclusions: The results suggest that long-term exposure to PM10 and O3 is associated with uncontrolled asthma in adults, defined by symptoms, exacerbations and lung function. [ABSTRACT FROM AUTHOR]

Summary: Background: The aims were to assess 1) the relationship of asthma control assessed by combining epidemiological survey questions and lung function to Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled asthma reach similar generic HRQL levels as individuals without asthma. Methods: The analysis included 584 individuals without asthma and 498 with asthma who participated in the follow-up of the Epidemiological study on Genetics and Environment of Asthma (EGEA). Asthma control was assessed from survey questions and lung function, closely adapted from the 2006–2009 Global Initiative for Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1–7) and the generic SF-36 (scores range: 0–100) were used. Results: Adjusted mean total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9 and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p < 0.0001). The differences in SF-36 scores between individuals with controlled asthma and those without asthma were minor and not significant for the PCS (−1, p = 0.09), borderline significant for the MCS (−1.6, p = 0.05) and small for the 8 domains (<5.1) although statistically significant for 4 domains. Conclusion: These results support the discriminative properties of the proposed asthma control grading system and its use in epidemiology. [ABSTRACT FROM AUTHOR]

Background: The prevalence rates of smoking in subjects with asthma have frequently been reported as similar to those in the general population; however, available data are not up-to-date. There is only limited and somewhat conflicting information on the long-term effects of smoking on health outcomes among population-based cohorts of subjects with asthma. We aimed to investigate changes in smoking habits and their effects on forced expiratory volume in 1 s (FEV1) in subjects with asthma in comparison with the rest of the population, focusing on the healthy smoker effect. Methods: We studied 9,092 subjects without asthma and 1,045 with asthma at baseline who participated in both the European Community Respiratory Health Survey I (20-44 years old in 1991-1993) and II (1999-2002). Results: At follow-up, smoking was significantly less frequent among subjects with asthma than in the rest of the population (26 vs. 31%; p < 0.001). Subjects with asthma who were already ex-smokers at the beginning of the follow-up in the 1990s had the highest mean asthma score (number of reported asthma-like symptoms, range 0-5), probably as a result of the healthy smoker effect (2.80 vs. 2.44 in never smokers, 2.19 in quitters and 2.24 in smokers; p < 0.001). The influence of smoking on FEV1 decline did not depend on asthma status. Smokers had the highest proportion of subjects with chronic cough/phlegm (p < 0.01). Conclusion: One out of 4 subjects with asthma continues smoking and reports significantly more chronic cough and phlegm than never smokers and ex-smokers. This stresses the importance of smoking cessation in all patients with asthma, even in those with less severe asthma. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: To identify the baseline characteristics associated with suppurative complications in children with community-acquired primary pneumonia. Methods: A retrospective study included all children from 28 days to 15 years old, who presented with community-acquired pneumonia at two French hospitals from 1995 to 2003. Complicated pneumonia was defined by the presence of empyema and/or lung abscess. Results: Of 767 children with community-acquired pneumonia, 90 had suppurative complications: 83 cases of pleural empyema and seven cases of lung abscess. The mean prevalence of complicated pneumonia was 3% during the 1995–1998 period, and then steadily increased following a linear trend to reach 23% in 2003. Children with complicated pneumonia were older and had a longer symptomatic period preceding hospitalization. They were more likely to receive antibiotics, especially aminopenicillins (p < 0.01), and nonsteroidal anti-inflammatory drugs, especially ibuprofen (p < 0.001). In multivariable analysis, ibuprofen was the only preadmission therapy that was independently associated with complicated pneumonia [adjusted OR = 2.57 (1.51–4.35)]. Conclusion: This study confirms an association between the use of prehospital ibruprofen and suppurative pneumonic complications. [ABSTRACT FROM AUTHOR]

Summary: Background: A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort. Methods: A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990–94) and ECRHS-II (1998–2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants. Results: The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was −2% (95% CI: −9.5, 5.5), 7.5% (−2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08–10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11–3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed. Conclusions: Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical communication. [Copyright &y& Elsevier]

Summary: Reduced pulmonary function is an important predictor of cardiovascular morbidity and mortality. The mechanisms underlying this association are unknown but may involve systemic inflammation. We assessed the cross-sectional and longitudinal relationships between C-reactive protein (CRP) levels and forced expiratory volume in 1s (FEV1) and its decline in the general population, over a period of 8.5 years. The analyzes were based on 531 subjects (mean age at baseline: 37±7 years, 50% women and 42% non-smokers), recruited at two French centers participating in the European Community Respiratory Health Survey. Lung function was expressed as a percentage of predicted FEV1. CRP was measured centrally, by means of a highly sensitive assay. In cross-sectional analysis, FEV1 as a % of predicted values was negatively associated with serum CRP concentration (). Multivariate adjustment did not alter these results (). In longitudinal analysis, annual FEV1 decline tended to increase from the lower to the upper tertile for baseline CRP concentration but the association was borderline significant (). Mean values of annual FEV1 decline were 26±32, 31±32, and 34±32ml/year for the lower, middle and upper tertiles of baseline CRP concentration, respectively, after adjusting for potential confounders (). Changes in CRP levels during follow-up were associated with annual FEV1 decline. The mean annual FEV1 declines in subjects with increasing CRP, in those with stable CRP and in those with decreasing CRP were 36±31, 30±31 and 24±31ml/year, respectively (). These findings were not affected by adjustment for potential confounders (). In conclusion, increases in CRP levels over time were associated with a steeper FEV1 decline. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Background Cross-sectional studies have reported a lower prevalence of sensitization in older adults, but few longitudinal studies have examined whether this is an aging or a year-of-birth cohort effect. Objective We sought to assess changes in sensitization and total IgE levels in a cohort of European adults as they aged over a 20-year period. Methods Levels of serum specific IgE to common aeroallergens (house dust mite, cat, and grass) and total IgE levels were measured in 3206 adults from 25 centers in the European Community Respiratory Health Survey on 3 occasions over 20 years. Changes in sensitization and total IgE levels were analyzed by using regression analysis corrected for potential differences in laboratory equipment and by using inverse sampling probability weights to account for nonresponse. Results Over the 20-year follow-up, the prevalence of sensitization to at least 1 of the 3 allergens decreased from 29.4% to 24.8% (−4.6%; 95% CI, −7.0% to −2.1%). The prevalence of sensitization to house dust mite (−4.3%; 95% CI, −6.0% to −2.6%) and cat (−2.1%; 95% CI, −3.6% to −0.7%) decreased more than sensitization to grass (−0.6%; 95% CI, −2.5% to 1.3%). Age-specific prevalence of sensitization to house dust mite and cat did not differ between year-of-birth cohorts, but sensitization to grass was most prevalent in the most recent ones. Overall, total IgE levels decreased significantly (geometric mean ratio, 0.63; 95% CI, 0.58-0.68) at all ages in all year-of-birth cohorts. Conclusion Aging was associated with lower levels of sensitization, especially to house dust mite and cat, after the age of 20 years. [ABSTRACT FROM AUTHOR]

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 (FEF 25-75 ) was associated with the persistence of current asthma over 20 years and the subsequent risk for uncontrolled asthma independently of FEV 1 . 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 FEF 25-75 decreased by 10% of predicted value. Results A reduced level of FEF 25-75 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 FEV 1 and in participants with FEV 1 of greater than 80% of predicted value. A reduced FEF 25-75 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 FEF 25-75 , might contribute to the long-term persistence of asthma and the subsequent risk for poor asthma outcomes independently from effects of the large airways. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [Copyright &y& Elsevier]

Summarizes results of the Epidemiologic Study on the Genetics and Environment of Asthma (EGEA), which was planned to assess genetic and environmental risk factors and their interactions in patients with asthma and for the two related traits of bronchial hyperresponsiveness and atopy. Smoking; Occupational exposures to asthma; Segregation analyses of IgE.

Abstract: Background: Spatially-resolved air pollution models can be developed in large areas. The resulting increased exposure contrasts and population size offer opportunities to better characterize the effect of atmospheric pollutants on respiratory health. However the heterogeneity of these areas may also enhance the potential for confounding. We aimed to discuss some analytical approaches to handle this trade-off. Methods: We modeled NO2 and PM10 concentrations at the home addresses of 1082 pregnant mothers from EDEN cohort living in and around urban areas, using ADMS dispersion model. Simulations were performed to identify the best strategy to limit confounding by unmeasured factors varying with area type. We examined the relation between modeled concentrations and respiratory health in infants using regression models with and without adjustment or interaction terms with area type. Results: Simulations indicated that adjustment for area limited the bias due to unmeasured confounders varying with area at the costs of a slight decrease in statistical power. In our cohort, rural and urban areas differed for air pollution levels and for many factors associated with respiratory health and exposure. Area tended to modify effect measures of air pollution on respiratory health. Conclusions: Increasing the size of the study area also increases the potential for residual confounding. Our simulations suggest that adjusting for type of area is a good option to limit residual confounding due to area-associated factors without restricting the area size. Other statistical approaches developed in the field of spatial epidemiology are an alternative to control for poorly-measured spatially-varying confounders. [Copyright &y& Elsevier]