(I. Annesi-Maesano & A.M. Magnier)

The main objective of this pole is to identify epigenetic, genetic and environmental factors at the origin of chronic allergic and respiratory diseases (asthma, rhinitis and chronic obstructive pulmonary disease) to understand the heterogeneity of these diseases.

Specific objectives

a) Determine interactions of epigene / gene-environment type
b) Assess the effects of exposure to multi pollution mixture on asthma and COPD
c) Develop a reference methodology for screening respiratory diseases related to air pollution in general practice.

Three are the main projects to be developed within this theme between 2014-8:

a) Epigene/Gene - environment interactions: The EDEN study of which Dr Charles is the PI and EPAR WP leader is the first cohort study conducted in France on ante and post-natal determinants of psychomotor development and child health. Its objective is to better establish the importance of early determinants of the health of individuals, particularly in relation to environmental factors that influence the course of childhood and adult life. An important part of the work of this cohort is devoted to understanding the development of asthma and allergies. In this cohort, approximately 1200 children (including prenatal) were prospectively followed for 8 years. This study is part of European projects MeDALL, ENRIECO and Chicos. EDEN cohort will be used for the development of two themes:
i) Evolutionary genetics and epigenetics of asthma and allergies which were inaugurated in the project Medall (Mechanisms of the Development of Allergy)
ii) Interactions of epigene – environment type, early life exposure to outdoor air pollution and diet in particular, which should determine whether air pollution plays a causal role in these multifactorial diseases. The study will be multicentric and thus very informative. Gene-environment interactions will also look for in the context of asthma and COPD among farmers of the FERMA study where air pollution was assessed quantitatively (see below).

b) Exposure to multi-pollution and asthma and COPD phenotypes in urban and rural: National Six Cities and Child'asthma and FERMA studies and international HESE, HESEINT and SINPHONIE studies subsidized by DG-SANCO will allow investigating the effects of exposure to multiple air pollution on respiratory and allergic phenotypes via the inclusion of multiple pollutants environments (home,
school, city ...), the cumulative estimate of exposure to air pollution and especially exposure to the multi-pollution. This should help us to understand the mechanisms underlying these pathologies. In fact, while the effect of one pollutant may be absent, it may manifest when it encounters other pollutants1. Note that the study FERMA which implementation was funded by ANSES takes place in agricultural settings, which is an interesting model for studying the development of allergic and respiratory phenotypes / endotypes in rural areas that are very specific, since compared to the general urban population children who grew up on a farm are less allergic and farmers develop COPD despite the fact they smoke significantly less. We hypothesized that rural conditions result in prolonged exposure to chemical pollutants (BTX, VOC, PM ...) and biological contaminants (mold, microbial VOCs, endotoxins ...) in rural areas. For the first time the phenotyping of allergic rhinitis according to its severity will be achieved by clustering techniques.

c) Interest and setting up a screening for indoor air pollution (Head AM Magnier): The prevalence of asthma has doubled worldwide in recent decades2. This increase is predominant in children but also affects the adult population, with a recent trend towards stabilization in all developed countries. As previously mentioned, the rapid increase (a period of twenty to forty years) suggests that environmental or behavioural changes may be responsible. The role of exposure to tobacco, including second hand smoke, and maternal smoking in early life can partly explain this trend. Pollution of indoor and outdoor air is also a factor implicated in the increase of this pathology3 4 5. Asthma is one of the leading causes of consultation in general practice (http://www.irdes.fr/Publications/2010/Qes152.pdf). Recent developments in knowledge and the role accorded increasingly important environmental factors in the onset or worsening of asthma requires further research in primary care: What are the environmental risk factors associated with the occurrence an asthma attack? What screening methods can be implemented in primary care? What preventive or therapeutic measures can improve asthma symptoms? Since the establishment in 2010, the group health environment within the Department of General Practice, Faculty of Medicine Saint-Antoine, has deepened the links between exposure to environmental pollutants and child and adults health. This work, presented as theses exercise of medicine, is currently being published6. In addition, two other studies have assessed the knowledge of GPs in terms of health consequences of indoor air pollution and passive smoking in particular (work in progress for submission). Planned epidemiological studies conducted in primary care will help to better define target populations requiring assessment of their indoor environment. Then, intervention studies will compare supported specific care delivered in routine practice. New diagnostic and therapeutic possibilities require close collaboration between general practitioners, pulmonologists, medical advisors in indoor environment and specialized regional services (such as the Hygiene Laboratory of the City of Paris). These aspects will be considered so as to provide screening and appropriate management of these  patients within the limits of available local resources. Lastly, a medico-economic evaluation will specify the interest and feasibility of such screening in general practice. The aims of the group are to assess a a priori screening for indoor air pollution but also to assess its economic interest. This dual assessment was the subject of several recent publications of the HAS (French High Authority of Health). Screening, like all health actions, must prove its efficiency. Effective for the patient, it must be good for the community. This would be evaluated.





1Billionnet C, de Blay, Kirchner S, Annesi-Maesano I. Synergetic effects of VOCs and allergens in a general population. J Allergy Clin Immunol (submitted)

2Baiz N, Annesi-Maesano. Is the asthma epidemics still ascending. Clin Chest Med 201233(3):419-29.

3Brauer M, Hoek G, Smit HA, de Jongste JC, Gerritsen J, Postmae DS, Kerkhof M, Brunekreef B. Air pollution and development of asthma, allergy and infections in a birth cohort. Eur Respir J 2007, 29: 879–888.

4Billionnet C, Gay E, Kirchner S, Leynaert B, Annesi-Maesano I. Quantitative assessments of indoor air pollution and respiratory health in a population-based sample of French dwellings. Environ Res. 2011 Apr;111(3):425-34.

5Gehring 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. Eur Respir J 2002, 19(4):690-8. 8 Mitha, Ibanez, Lafortune, Annesi-Maesano, Magnier. Pollution de l'air intérieur et asthme chez l'adulte. Rev Mal Resp (sous presse)