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The prevalence of asthma has increased rapidly since the early 1970s, and only changes in exposure to environmental factors; which go together with changes in lifestyle, are likely to explain such a rapid increase. Exposure to allergens is a risk factor for allergic sensitization, and allergic sensitization is a risk factor for allergic asthma. However, apart from indoor mold exposure as a risk factor for childhood asthma, there is insufficient evidence to conclude that the associations between allergen exposure and asthma development are causal. A new challenge for research is to analyze the huge amount of data derived from the metagenomic characterization of the environmental and human microbiome, to understand the role of interactions between viruses, bacteria and allergens in the development of asthma. It is recognized that prenatal and postnatal exposure to air pollution and maternal smoking increase the risk of developing asthma in children. In adults, the data are scarce and the results remain controversial as regards these exposures and asthma incidence. Further research is needed to appraise the effect of exposure to phenols, phthalates and perfluorinated compounds, which are widespread in the environment and may be associated with asthma, especially in children. Frequent use of chemicals for home cleaning especially in the form of sprays - which is a common practice at the population level - is a risk factor for the development of adult asthma. The domestic use of cleaning products might also be a risk factor for asthma in children exposed at home. The chemicals involved in these relationships are still to be identified. Occupational asthma is a major phenotype of adult asthma. A significant part of these asthma cases might relate to occupational exposure to cleaning products. While there is evidence of associations between diet during pregnancy or during childhood and the risk of developing asthma in children, the data in adults are insufficient. Beyond genetic factors, body composition is influenced by dietary choices and physical activity. Further research is needed to clarify the complex interplay between these nutritional factors and asthma development. The new challenge for research is to decipher the role of all the environmental factors to which the individual is exposed since conception ("exposome") in the development of asthma, using a holistic approach., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

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.)

Epidemiological research is mostly based on observational studies. Whether such studies can provide evidence of causation remains discussed. Several causal analysis methods have been developed in epidemiology. This paper aims at presenting an overview of these methods: graphical models, path analysis and its extensions, and models based on the counterfactual approach, with a special emphasis on marginal structural models. Graphical approaches have been developed to allow synthetic representations of supposed causal relationships in a given problem. They serve as qualitative support in the study of causal relationships. The sufficient-component cause model has been developed to deal with the issue of multicausality raised by the emergence of chronic multifactorial diseases. Directed acyclic graphs are mostly used as a visual tool to identify possible confounding sources in a study. Structural equations models, the main extension of path analysis, combine a system of equations and a path diagram, representing a set of possible causal relationships. They allow quantifying direct and indirect effects in a general model in which several relationships can be tested simultaneously. Dynamic path analysis further takes into account the role of time. The counterfactual approach defines causality by comparing the observed event and the counterfactual event (the event that would have been observed if, contrary to the fact, the subject had received a different exposure than the one he actually received). This theoretical approach has shown limits of traditional methods to address some causality questions. In particular, in longitudinal studies, when there is time-varying confounding, classical methods (regressions) may be biased. Marginal structural models have been developed to address this issue. In conclusion, "causal models", though they were developed partly independently, are based on equivalent logical foundations. A crucial step in the application of these models is the formulation of causal hypotheses, which will be a basis for all methodological choices. Beyond this step, statistical analysis tools recently developed offer new possibilities to delineate complex relationships, in particular in life course epidemiology., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

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.

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.