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Background: Evidences that oxidative stress plays a role in the associations between outdoor air pollution and asthma are growing. We aimed to study the role of plasma fluorescent oxidation products levels (FlOPs; an oxidative stress-related biomarker), as potential mediators, in the associations between outdoor air pollution and persistent asthma., Methods: Analyses were conducted in 204 adult asthmatics followed up in the French case-control and family study on asthma (EGEA; the Epidemiological study of the Genetic and Environmental factors of Asthma). Persistent asthma was defined as having current asthma at EGEA2 (baseline, 2003-2007) and EGEA3 (follow-up, 2011-2013). Exposures to nitrogen dioxide, nitrogen oxides, road traffic, particulate matter with a diameter ≤ 10 μm (PM 10 ) and ≤ 2.5 μm were estimated by ESCAPE models (2009-2010), and ozone (O 3 ) by IFEN models (2004). We used a mediation analysis to assess the mediated effect by FlOPs levels and the interaction between FlOPs levels and air pollution., Results: FlOPs levels increased with PM 10 and O 3 (adjusted β = 0.04 (95%CI 0.001-0.08), aβ = 0.04 (95%CI 0.009-0.07) per 10 μg/m 3 , respectively), and the risk of persistent asthma increased with FlOPs levels (aOR = 1.81 (95%CI 1.08-3.02)). The risk of persistent asthma decreased with exposures to NO 2 , NOx and PM 2.5 (aOR ranging from 0.62 to 0.94), and increased with exposures to PM 10 , O 3 , O 3-summer and road traffic, the greater effect being observed for O 3 (aOR = 1.78, 95% CI 0.73-4.37, per 10 μg/m 3 ). Using mediation analysis, we observed a positive total effect (aOR = 2.16, 95%CI 0.70-11.9), a positive direct effect of O 3 on persistent asthma (OR = 1.68, 95%CI 0.57-7.25), and a positive indirect effect mediated by FIOPs levels (aOR = 1.28 (95%CI 1.01-2.29)) accounting for 41% of the total effect., Conclusions: Our results add insights on the role of oxidative stress in the association between air pollution and persistent asthma.

Background: With population aging, further asthma research is needed in the elderly., Objective: We assessed the relevance of the controller-to-total asthma medication ratio and its fluctuations over time to identify participants with a subsequent risk of poor asthma-related outcomes among well-characterized elderly women., Methods: We studied 4,328 women with ever asthma (69.6 ± 6.1 years) from the Asthma-E3N study (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale), which combined drug claims data since 2004 with prospective individual characteristics. The levels of the yearly controller-to-total asthma medication ratio from 2004 to 2011 were included in latent class analysis to identify groups of women characterized by specific long-term fluctuations of the ratio. Multiple regression models estimated the subsequent risk of uncontrolled asthma, asthma attacks, asthma exacerbations, and poor asthma-related quality of life associated with the level and the fluctuations of the ratio., Results: A short-term (12 months) ratio below 0.5 was associated with a higher risk of subsequent uncontrolled asthma, asthma attacks, asthma exacerbations (odds ratio [95% confidence interval (CI)] = 2.13 [1.41; 3.23], 1.51 [1.01; 2.26], and 2.18 [1.37; 3.44], respectively), and a lower total asthma quality of life questionnaire score (β [95% CI] = -0.49 [-0.68; -0.29]). The analysis of the long-term fluctuations of the ratio identified 5 profiles ("Never regular treatment," 53.2%; "Persistent high ratio," 21.8%; "Increasing ratio," 4.4%; "Initiating treatment," 8.8%; "Treatment discontinuation," 11.8%). The subsequent risk of poor asthma-related outcomes was significantly higher in profiles characterized by no or interrupted asthma maintenance therapy over time, compared with the "Persistent high ratio" group., Conclusions: The level and the long-term fluctuations of the controller-to-total asthma medication ratio predict poor asthma-related outcomes in elderly women., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Multimedication related to multimorbidity is common in the elderly with asthma. We aimed at comprehensively characterising medications used by elderly women and assessing how multimedication impacts on asthma prognosis.We performed network-based analyses on drug administrative databases to visualise the prevalence of drug classes and their interconnections among 17 458 elderly women from the Asthma-E3N study, including 4328 women with asthma. Asthma groups sharing similar medication profiles were identified by a clustering method relying on all medications and were studied in association with adverse asthma events (uncontrolled asthma, attacks/exacerbations and poor asthma-related quality of life).The network-based analysis showed more multimedication in women with asthma than in those without asthma. The clustering method identified three multimedication profiles in asthma: "Few multimorbidity-related medications" (43.5%), "Predominantly allergic multimorbidity-related medications" (32.8%) and "Predominantly metabolic multimorbidity-related medications" (23.7%). Compared with women belonging to the "Few multimorbidity-related medications" profile, women belonging to the two other profiles had an increased risk of uncontrolled asthma and asthma attacks/exacerbations, and had lower asthma-related quality of life.The integrative data-driven approach on drug administrative databases identified specific multimorbidity-related medication profiles that were associated with poor asthma prognosis. These findings support the importance of multimorbidity in the unmet needs in asthma management., Competing Interests: Conflict of interest: S. Chanoine reports personal fees (board membership) from AstraZeneca, and nonfinancial support (travel/accommodation/meeting expenses) from Boehringer Ingelheim, Actelion Pharmaceuticals and MSD, outside the submitted work. I. Pin reports travel grants and presentation fees from Novartis and AstraZeneca, and fees for training courses from Vertex, outside the submitted work. C. Pison has received grants and lectures fees from GlaxoSmithKline, AstraZeneca, Novartis and BIF, as well as speaker fees and fees for meeting participation from GlaxoSmithKline, AstraZeneca, Novartis, BIF and Teva. J. Bousquet reports personal fees (scientific and advisory boards) from Almirall, Meda, Merck, MSD, Novartis, Sanofi-Aventis, Takeda, Teva and Uriach, as well as personal fees (lecture fees) from Almirall, AstraZeneca, Chiesi, GlaxoSmithKline, Meda, Menarini, Merck, MSD, Novartis, Sanofi-Aventis, Takeda, Teva and Uriach, outside the submitted work. P. Bedouch reports fees for meeting expenses from Actelion Pharmaceuticals, outside the submitted work. R. Varraso reports grants from the Institut pour la Recherche en Santé Publique (IReSP), during the conduct of the study. V. Siroux reports personal fees (speakers honorarium) from Teva, AstraZeneca and Novartis, outside the submitted work., (Copyright ©ERS 2018.)

Associations between outdoor air pollution and asthma in adults are still scarce, and the underlying biological mechanisms are poorly understood. Our aim was to study the associations between 1) long-term exposure to outdoor air pollution and current asthma, 2) exhaled 8-isoprostane (8-iso; a biomarker related to oxidative stress) and current asthma, and 3) outdoor air pollution and exhaled 8-iso.Cross-sectional analyses were conducted in 608 adults (39% with current asthma) from the first follow-up of the French case-control and family study on asthma (EGEA; the Epidemiological study of the Genetic and Environmental factors of Asthma). Data on nitrogen dioxide, nitrogen oxides, particulate matter with a diameter ≤10 and ≤2.5 µm (PM 10 and PM 2.5 ), road traffic, and ozone (O 3 ) were from ESCAPE (European Study of Cohorts for Air Pollution Effects) and IFEN (French Institute for the Environment) assessments. Models took account of city and familial dependence.The risk of current asthma increased with traffic intensity (adjusted (a)OR 1.09 (95% CI 1.00-1.18) per 5000 vehicles per day), with O 3 exposure (aOR 2.04 (95% CI 1.27-3.29) per 10 µg·m -3 ) and with exhaled 8-iso concentration (aOR 1.50 (95% CI 1.06-2.12) per 1 pg·mL -1 ). Among participants without asthma, exhaled 8-iso concentration increased with PM 2.5 exposure (adjusted (a)β 0.23 (95% CI 0.005-0.46) per 5 µg·m -3 ), and decreased with O 3 and O 3-summer exposures (aβ -0.20 (95% CI -0.39- -0.01) and aβ -0.52 (95% CI -0.77- -0.26) per 10 µg·m -3 , respectively).Our results add new insights into a potential role of oxidative stress in the associations between outdoor air pollution and asthma in adults., Competing Interests: Conflict of interest: V. Siroux reports personal fees (speaker honorarium) from Teva, AstraZeneca and Novartis, outside the submitted work., (Copyright ©ERS 2018.)

Introduction and Methods: The EGEA study (epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), which combines a case-control and a family-based study of asthma case (n=2120 subjects) with three surveys over 20 years, aims to identify environmental and genetic factors associated with asthma and asthma-related phenotypes. We summarize the results of the phenotypic characterization and the investigation of environmental and genetic factors of asthma and asthma-related phenotypes obtained since 2007 in the EGEA study (42 articles)., Results: Both epidemiological and genetic results confirm the heterogeneity of asthma. These results strengthen the role of the age of disease onset, the allergic status and the level of disease activity in the identification of the different phenotypes of asthma. The deleterious role of active smoking, exposure to air pollution, occupational asthmogenic agents and cleaning products on the prevalence and/or activity of asthma has been confirmed. Accounting for gene-environment interactions allowed the identification of new genetic factors underlying asthma and asthma-related traits and better understanding of their mode of action., Conclusion: The EGEA study is contributing to the advances in respiratory research at the international level. The new phenotypic, environmental and biological data available in EGEA study will help characterizing the long-term evolution of asthma and the factors associated to this evolution., (Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

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.

Although interest in biomarkers in the nitrate-nitrite-NO pathway has recently increased, associations between nitrite (NO2(-)) and nitrate (NO3(-)), and asthma, allergic sensitisation and rhinitis remain unclear. The study aimed to evaluate the associations between NO2(-)/NO3(-) and exhaled fraction of nitric oxide (FeNO) levels with asthma, allergic sensitisation and rhinitis. Plasma and exhaled breath condensate (EBC) NO2(-)/NO3(-) and FeNO levels were measured in 523 adults of the French Epidemiological study on Genetics and Environment of Asthma. Allergic sensitisation was defined by a positive skin prick test for at least one aeroallergen. Subjects were classified as non-sensitised, sensitised and as having allergic rhinitis. Plasma NO2 (-)/NO3(-) level was unrelated to any disease phenotypes. EBC NO2(-)/NO3(-) level was unrelated to any asthma phenotypes. EBC NO2(-)/NO3(-) and FeNO levels were correlated in sensitised subjects only (r = 0.21 ± 0.10, p=0.01). EBC NO2(-)/NO3(-) and FeNO levels were higher in sensitised than in non-sensitised subjects (adjusted geometric mean (95% CI): 2.36 (1.96-2.84) versus 1.72 (1.38-2.14) μmol per mg proteins, p=0.008; and 18.3 (16.7-20.0) versus 14.8 (13.3-16.5) ppb, p=0.0006, respectively), with gradual relationships from sensitised subjects to those with allergic rhinitis (p<0.0001). Results suggest that EBC NO2(-)/NO3(-) and FeNO levels may be considered as biological markers of intensity of allergic sensitisation and rhinitis., (©ERS 2014.)

The aim of the study was to identify genetic variants associated with refined asthma phenotypes enabling multiple features of the disease to be taken into account. Latent class analysis (LCA) was applied in 3001 adults ever having asthma recruited in the frame of three epidemiological surveys (the European Community Respiratory Health Survey (ECRHS), the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) and the Epidemiological Study on the Genetics and Environment of Asthma (EGEA)). 14 personal and phenotypic characteristics, gathered from questionnaires and clinical examination, were used. A genome-wide association study was conducted for each LCA-derived asthma phenotype, compared to subjects without asthma (n=3474). The LCA identified four adult asthma phenotypes, mainly characterised by disease activity, age of asthma onset and atopic status. Associations of genome-wide significance (p<1.25 × 10(-7)) were observed between "active adult-onset nonallergic asthma" and rs9851461 flanking CD200 (3q13.2) and between "inactive/mild nonallergic asthma" and rs2579931 flanking GRIK2 (6q16.3). Borderline significant results (2.5 × 10(-7) < p <8.2 × 10(-7)) were observed between three single nucleotide polymorphisms (SNPs) in the ALCAM region (3q13.11) and "active adult-onset nonallergic asthma". These results were consistent across studies. 15 SNPs identified in previous genome-wide association studies of asthma have been replicated with at least one asthma phenotype, most of them with the "active allergic asthma" phenotype. Our results provide evidence that a better understanding of asthma phenotypic heterogeneity helps to disentangle the genetic heterogeneity of asthma.

Objectives: The healthy worker effect usually leads to underestimation of the association between occupational exposure and asthma. The role of irritants in work-related asthma is disputed. We estimated the effect of occupational exposure on asthma expression in a longitudinal study, using marginal structural modelling to control for the healthy worker effect., Methods: Analyses included 1284 participants (17-79 years, 48% men) from the follow-up (2003-2007) of the French Epidemiological study on the Genetics and Environment of Asthma (case-control study). Age at asthma onset, periods with/without attacks over lifetime and occupational history were recorded retrospectively. Exposures to known asthmagens, irritants or low level of chemicals/allergens were evaluated through a job-exposure matrix. The job history was reconstructed into 5-year intervals., Results: Thirty-one per cent of subjects had ever been exposed to occupational asthmagens. Among the 38% of subjects who had asthma (ever), presence of attacks was reported in 52% of all time periods. Using standard analyses, no association was observed between exposure to known asthmagens (OR (95% CI): 0.99 (0.72 to 1.36)) or to irritants/low level of chemicals/allergens (0.82 (0.56 to 1.20)) and asthma attacks. Using a marginal structural model, all associations increased with suggestive evidence for known asthmagens (1.26 (0.90 to 1.76)), and reaching statistical significance for irritants/low level of chemicals/allergens (1.56 (1.02 to 2.40))., Conclusions: The healthy worker effect has an important impact in risk assessment in work-related asthma studies. Marginal structural models are useful to eliminate imbalances in exposure due to disease-driven selection. Results support the role of irritants in work-related asthma.

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 NO(2), O(3) and PM(10) and asthma control in the follow-up of the Epidemiological study on the Genetics and Environment of Asthma (EGEA2) (2003-2007)., Methods: Modelled outdoor NO(2), O(3) and PM(10) estimates 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 2006-2009 Global 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 NO(2) (n=465), 46 (41-52) for O(3) and 21 (18-21) for PM(10) (n=481). In total, 44%, 29% and 27% had controlled, partly controlled and uncontrolled asthma, respectively. The ordinal ORs for O(3) and PM(10) with asthma control were 1.69 (95% CI 1.22 to 2.34) and 1.35 (95% CI 1.13 to 1.64), respectively. When including both pollutants in the same model, both associations persisted. Associations were not modified by sex, smoking status, use of inhaled corticosteroids, 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 PM(10) and O(3) is associated with uncontrolled asthma in adults, defined by symptoms, exacerbations and lung function.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Information on the healthy worker hire effect in relation to asthma is scant. We aimed to assess whether and how childhood asthma-related characteristics (before hire) relate to occupational exposures at first hire. Analyses were conducted in 298 children examined at the first survey of the Epidemiological Study on the Genetics and Environment of Asthma (1991-1995), who reported a training period or a job at follow-up in 2003-2007 (aged 17-29 yrs; 53% males). Exposure likelihood to dust, gases and/or fumes in their first occupation was estimated by the ALOHA job exposure matrix. Asthma before the first occupation and two asthma classifications for severity (Global Initiative for Asthma 2002 guidelines) and symptoms were defined by questionnaire. In their first job, 47% of subjects were exposed. After adjustment (age, sex and education), pre-hire onset asthmatics (59%) were nonsignificantly less likely to be exposed (OR 0.67, 95% CI 0.41-1.11). Associations were stronger when considering those with severe asthma or high symptom score in childhood (OR 0.27 (95% CI 0.11-0.63) and OR 0.49 (95% CI 0.25-0.99), respectively). The association was observed in those who completed a university degree (OR 0.55, 95% CI 0.29-1.04) but not in the others (OR 0.98, 95% CI 0.44-2.22), with consistent results for all asthma characteristics. Results suggest a healthy worker hire effect in subjects with more severe or more symptomatic asthma in childhood. Education may modulate self-selection.

Background: Studies of the effects of air pollutants on birth weight often assess exposure with networks of permanent air quality monitoring stations (AQMSs), which have a poor spatial resolution., Objective: We aimed to compare the exposure model based on the nearest AQMS and a temporally adjusted geostatistical (TAG) model with a finer spatial resolution, for use in pregnancy studies., Methods: The AQMS and TAG exposure models were implemented in two areas surrounding medium-size cities in which 776 pregnant women were followed as part of the EDEN mother-child cohort. The exposure models were compared in terms of estimated nitrogen dioxide (NO2) levels and of their association with birth weight., Results: The correlations between the two estimates of exposure during the first trimester of pregnancy were r = 0.67, 0.70, and 0.83 for women living within 5, 2, and 1 km of an AQMS, respectively. Exposure patterns displayed greater spatial than temporal variations. Exposure during the first trimester of pregnancy was most strongly associated with birth weight for women living < 2 km away from an AQMS: a 10-µg/m3 increase in NO2 exposure was associated with an adjusted difference in birth weight of -37 g [95% confidence interval (CI), -75 to 1 g] for the nearest-AQMS model and of -51 g (95% CI, -128 to 26 g) for the TAG model. The association was less strong (higher p-value) for women living within 5 or 1 km of an AQMS., Conclusions: The two exposure models tended to give consistent results in terms of association with birth weight, despite the moderate concordance between exposure estimates.

There is ongoing debate as to how asthma should be defined in order to forward understanding of the underlying mechanisms. The aim of the present study was to build quantitative scores of asthma and asthma severity and to assess whether refinement of disease phenotypes can facilitate the identification of chromosomal regions harbouring susceptibility genes. A genome-wide linkage scan was conducted in 110 families with at least two asthmatic siblings (n = 508) from the French Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The phenotypes studied were an asthma severity score (assessed among asthmatics by combining clinical data and treatment), forced expiratory volume in one second (FEV(1)) and an asthma score (including both asthmatics and nonasthmatics and representing the whole disease spectrum). This analysis showed genome-wide suggestive evidence of linkage of the asthma score to 18p11, a novel region undetected in a previous screen of dichotomous asthma. There was potential linkage of 2p23 to asthma severity score and of three regions (1p36, 2q36 and 6q14) to FEV(1). Moreover, FEV(1) appeared to have no genetic determinant in common with asthma severity and asthma scores. Asthma and asthma severity quantitative scores revealed new regions of linkage and thus provide support for considering these phenotypes in future genetic studies.

Although many genome screens have been conducted for asthma as a binary trait, there is limited information regarding the genetic factors underlying variation of asthma expression. Phenotypes related to variable disease expression include time to asthma onset and variation in clinical expression as measured by an asthma score built from EGEA data. A recent genome scan conducted for this score led to detection of a new region (18p11) not revealed by analysis of dichotomous asthma. Our goal was to characterize chromosomal regions harboring genes underlying time to asthma onset and to search for pleiotropic QTL influencing both time to asthma onset and the asthma score. We conducted a genome-wide linkage screen for time to asthma onset, modeled by martingale residuals from Cox survival model, in EGEA families with at least two asthmatic sibs. This was followed by a bivariate linkage scan of these residuals and asthma score. Univariate linkage analysis was performed using the Maximum Likelihood Binomial method that we extended to bivariate analysis. This screen revealed two regions potentially linked to time to asthma onset, 1p31 (LOD = 1.70, P = 0.003) and 5q13 (LOD = 1.87, P = 0.002). Bivariate linkage analysis led to a substantial improvement of the linkage signal on 5q13 (P = 0.00007), providing evidence for a pleiotropic QTL influencing both variation of time to asthma onset and of clinical expression. Use of quantitative phenotypes of variable disease expression and suitable statistical methodology can improve the power to detect new regions harboring genes which may play an important role in onset and course of disease.

Introduction: EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article., Methods and Results: The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis., Conclusions: New hypothesis will be tested in the near future from the second stage of this survey.

Rationale: The severity of asthma has been defined by various criteria in epidemiology, but their relationships have been rarely studied., Material and Methods: The interrelationships between various asthma severity criteria (clinical severity in the past 12 months) (score 0-7), functional (FEV1), therapy (inhaled steroids used in the past 12 months) and hospitalization during life were studied. Bivariate (OR) and multivariate (factorial analyses, log-linear models) analyses were applied in asthmatic children (n=135) and adults (n=213) recruited in chest clinics for the EGEA study (Epidemiological Study on the Genetics and Environment of Asthma)., Results: In asthmatics, the proportion of severe asthma was highly dependent on the definition used. Whatever the statistical method used, FEV1 in children was unrelated to treatment, hospitalization and the clinical score. In adults, the clinical score was not associated with hospitalization, treatment and FEV1, these last three criteria being highly related to each other., Conclusion: Results support the hypothesis of the multidimensional character of severity of asthma.

The aim of this study was to assess the short-term reproducibility and the validity of reported ETS (environmental tobacco smoke) exposure, with a special emphasis on the potential misclassification related to personal or family history of asthma. Analyses were based on the data on the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA), a case-control study of asthma that included first degree relatives of asthmatic cases. The study was comprised of 348 families of asthmatics recruited in six chest clinics throughout France and 416 population-based controls. For studying the validity of ETS reports, personal active smoking histories reported by family members were taken as reference. The reproducibility of ETS exposure report was good, and independent of asthma. The validity of the report of maternal and paternal smoking in childhood and spouse smoking during life was high (overall agreement > or = 84%). Mothers of asthmatic children significantly underreported their smoking habits when questioned on their children's passive tobacco exposure. Offspring of parents who had stopped smoking underestimated their ETS exposure in childhood. In conclusion, interviews with mothers on their personal active smoking habits may provide a more accurate estimate of their asthmatic child's passive exposure than asking mothers specifically about their children's passive exposure. There was no indication that asthma status (either of the parent/spouse or of the respondent) by itself influences the report of ETS exposure during childhood or adulthood.

The French co-operative epidemiological study EGEA realised in 1991/95 combines a case control study and a study of the families of asthmatic cases. A synthesis of the results already obtained is presented. Smoking was related to IgE, even in asthmatics and was clearly related to the clinical severity of asthma, an aspect insufficiently taken into account. The relationships of occupational exposures to asthma have been assessed using a job exposure matrix. Segregation analyses on IgE have shown, after correction for the mode of ascertainment, the existence of a dominant major gene and familial residual correlation. A systematic genome screen realised in families with 2 asthmatic siblings showed linkage of various regions in the genome implicated to asthma or related phenotypes (1p, 11p, 11q, 12q, 13q, 17q, 19q), coherent with genome screens realised in other studies. Regarding candidate genes, no association was evidenced between asthma and the AF508 mutation of the cystic fibrosis gene. The analysis is still in progress by studies on the heterogeneity of asthma with refined genetic studies and by searching to integrate results regarding environmental and genetic factors and studying their interactions.