On-going projects

Project investigator: B Jacquemin et R Nadif
Places of project executions: Equipe d’épidémiologie respiratoire intégrative, CESP, Villejuif
Funding: Université Paris-Saclay, Bourse de Thèse, Marine Savouré, aide financière individuelle à la formation par la recherche financée par l’agence de l’environnement et la maitrise de l’énergie (ADEME)
Partners: groupe ‘Phénotype’

Rhinitis is a disease characterized by inflammation of the nasal cavity and is associated with symptoms such as sneezing, rhinorrhoea (i.e. a runny nose), congestion, and/or nasal pruritus (i.e. an itchy nose). Often trivialized, it is nevertheless very common, and has an individual and societal impact. There are different forms of rhinitis called endotypes which have their own characteristics depending on the biological and mechanistic pathways involved.
However, until now, rhinitis endotypes have been little studied in epidemiological studies. The objective of this project is therefore to identify and study the endotypes of rhinitis. For this purpose, an algorithmic approach (unsupervised approach) will be used based on biological data and data from the questionnaires of the EGEA2 participants. The identification and characterisation of rhinitis endotypes will provide new knowledge on rhinitis and thus potentially better prevention and treatment.

Project investigator: Raphaëlle Varraso
Places of project executions: INSERM UMR-S 1018, Center for Research in Epidemiology and Population Health (CESP), Integrative Respiratory Epidemiology team, Villejuif
Funding: NA
Partners: ‘Phenotypes’ group

Asthma is a multifactorial disease of the airways, with both genetic and environmental determinants. The prevalence of asthma has nearly doubled over the last decades, especially in Westernized countries and developing countries with rapid urbanization. This cannot be explained by genetics alone and it has been hypothesized that this increase is a consequence of changing environmental and/or lifestyle factors, including a modification of dietary habits (less fruit and vegetables, and more processed and ready-to-eat food). Up to now, the impact of specific foods and/or dietary patterns on asthma remains largely unknown.
As we do not consume isolated foods (such as apple) or nutrients (such as vitamin C), but meals consisting of a complex combination of foods, which themselves contain nutrients, studying overall diet through dietary scores has been proposed to evaluate dietary patterns. The most famous is the Mediterranean diet score which is based on a high consumption of fruits and seasonal vegetables, high consumption of whole grains cereals (including pasta, rice and bread), high consumption of legumes (lentils, chickpeas, beans...), fatty fish (sardines, mackerel, herring, salmon), fats from vegetable oils such as olive oil and nuts (walnuts, hazelnuts, almonds, pistachios...), and limited intake of red meat, dairy products (cheese, butter, cream), and refined and processed products (breakfast cereals, industrial bread, ready-made meals). However, research in nutritional epidemiology is evolving regarding knowledge between diet and health, and new dietary scores are frequently developed.

1) Plant-based diet (Master 2 AgroParisTech internship, 2021: Malek Fathallah; supervisors: Raphaëlle Varraso, Annabelle Bédard).
The term “plant-based diets” encompasses a wide range of dietary patterns that contain lower amounts of animal products and higher amounts of plant products, and are becoming increasingly popular. Current evidence clearly emphasizes the importance of a healthful plant-based dietary pattern because of its lower risk of diet-related chronic diseases, but also because of its lower environmental impact. Several dietary scores have been recently proposed in the literature to evaluate the nutritional quality of plant-based diets. It has been shown that a plant-based diet with low nutritional quality such as, for example a diet with a low intake of red meat but high intakes of chips and/or biscuits (unhealthful plant-based foods) was associated with a greater risk for cardiovascular diseases, underlying the importance of a differentiation of plant foods.
Thanks to detailed data on diet collected at EGEA2, the project aims to develop several dietary scores to evaluate the nutritional quality of plant-based diet, and to study their relationship with asthma symptoms and the evolution of asthma symptoms over time (between EGEA2 and EGEA3). We hypothesize that a greater adherence to a healthful version of a plant-based diet is associated with a decreased asthma symptoms risk, whereas adherence to an unhealthful version is associated with an increased asthma symptoms risk.

2) Diet with antioxidant or inflammatory capacity
Both oxidative stress and inflammation are two biological mechanism of interest in asthma. However, diet can be an important source of both oxidants and/or antioxidants, and of foods with inflammatory capacity. Dietary scores have been proposed to assess specific biological properties of diet, such as the dietary total antioxidant capacity (TAC) and the dietary inflammatory index (DII).
These dietary scores will be developed in collaboration with other nutritional epidemiology teams with which long-standing collaborations exist (Exposome and Heredity team, Inserm U1018, Villejuif; Nutritional Epidemiology Research team, Inserm U1153, Bobigny; Department of Nutritional Epidemiology, Harvard TH Chan School of Public Health, Boston, USA), and will be studied in relation with asthma.

Project investigator: Emmanuelle Bouzigon
Places of project executions: Université Paris Cité, Inserm UMR1124, Equipe Epidémiologie génomique des maladies multifactorielles
Funding: ANR GenCAST
Partners: Hanna Julienne, Institut Pasteur

Asthma is a heterogeneous disease with a large spectrum of clinical expression reflecting the multiple underlying physiopathological mechanisms or endotypes. Recent studies leveraged phenotypic and biological data to identify subtypes of individuals with asthma but have not included genetic data as a driving component of clustering process. This project aims to identify asthma endotypes by using clustering methods applied to genetic polymorphisms associated with multiple phenotypes involved in the pathophysiology of the disease. This project will allow better understanding of the genetic structure underlying asthma endotypes, and identifying more precisely the links between molecular pathways and clinical phenotypes, a key step towards the improvement and personalization of asthma management.

Project investigator: Valérie Siroux
Places of project executions: Equipe d’épidémiologie environnementale appliquée au développement et à la santé repiratoire, Institut pour l’Avancée des Biosciences, Grenoble; Université Paris Cité, Inserm UMR1124, Equipe Epidémiologie génomique des maladies multifactorielles
Funding: ANR-19-CE36-0005-01_NIRVANA
Partners: EGEA genetic group (Emmanuelle Bouzigon, Inserm U1124; Paris); Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University of Vienna (R Valenta)

Asthma is a frequent disabling chronic respiratory disease associated with high global costs ($81.9 billion in USA). In France, asthma prevalence in children is 11%. Asthma cannot be cured; therefore, prevention is thought to be the long-term solution for the asthma epidemic. Asthma results from interplays between environmental, lifestyle, genetic and epigenetic factors. For two environmental factors, respiratory allergens and respiratory viruses, strong association with asthma incidence or exacerbations is well documented. A few previous observations suggest that the host genotype plays an important role in the immune response of individual allergens and rhinovirus (RV), but these studies were limited in the assessment of allergen-specific and RV-specific immune responses. New technologies based on microarrays allow accurate and comprehensive characterization of hundreds allergen-specific and RV-specific antibody responses, and offer new avenues in the asthma epidemiological research.
Our main objective is to identify allergen-specific and RV-specific antibody responses associated with asthma and the host genomic determinants of these immune responses. The central hypothesis that the host genotype plays an important role in the effects of respiratory allergens and viruses in asthma is supported by several observations, but has still never been deeply addressed.
A detailed knowledge of the most harmful allergens and RV strains is mandatory for an appropriate diagnostic and preventive approach. Through detailed analysis of genetic factors underlying the antibody responses to allergens and RV involved in the development of asthma, the project will have major implications in deepening knowledge of the population at risk for allergic asthma and RV-induced asthma, which in turn will impact on the asthma management and prevention.

Project investigator: J Lepeule
Places of project executions: IAB, Inserm U1209, Equipe Epidémiologie environnementale appliquée au développement et à la santé respiratoire, Grenoble
Funding: Fondation de France CLIMATHES
Partners: groupe ‘Phénotypes’ (V Siroux)

Climate change is a major challenge for public health. Increasing temperatures and extreme weather events are sources of population health hazards, especially for the most vulnerable. The few studies that explored the links between ambient temperature and ventilatory function show contradictory results. However, they seem to agree on the fact that individuals suffering from asthma represent a vulnerable population. The CLIMATHES project seeks to test the hypothesis that higher temperatures and humidity levels are associated with lower ventilatory function in the short term.
The analysis will use data from all participants of the EGEA cohort who contributed to the first (EGEA1) or second (EGEA2) follow-up of the study. Exposures to ambient temperature and humidity are assessed at the participants' home address using models with fine spatial resolution (1km to 200m, Hough et al 2020) and the SAFRAN model. The forced expiratory volume (FEV1), which is an indicator of bronchial obstruction, is measured by spirometry. The analyses are conducted using a statistical model allowing to identify specific sensitivity windows for temperature and humidity exposure (generalized additive mixed effects model (GAMM) with distributed lags). We will also investigate whether some participants (e.g., asthmatics or asthmatics with specific forms of asthma) are more sensitive to temperature and humidity effects on respiratory health. Preliminary results indicate that an increase in temperature between days 3 and 17 prior to the lung function measurement is associated with a decrease in FEV1.