It is now well accepted that pathologies occurring at adult age have to be considered not only as consequences of adult events, but also as related to early events in life (ie during pregnancy or early childhood). Therefore, the general idea of our project is to determine the impacts of early exposome (in utero, kids up to 5 years old) on the onset of events (low birth weight, preterm birth, bronchopulmonary dysplasia, …) that constitute susceptibility factors to develop lung disease at adult age (such as chronic obstructive pulmonary disease - COPD), or to impact the course of genetic disease such as cystic fibrosis (CF). In the term "exposome", will be evaluated mainly air pollution, but also the noise, climate, life style (sports, …), socio-economic status, light exposure, air conditioning at home/work, … The project will use already constituted cohorts (pregnant mother and kids, from the general population, and from CF-constituted cohorts). On these cohorts, beside a thorough characterization of the exposome as well as clinical parameters, we will look for new biomarkers of exposome (focus on lipidomic and epigenetic analysis) to be linked with the onset of susceptibility factor, and develop a sensor based on these biomarkers. The relevance of the clinical findings will be addressed thanks to preclinical models exposed to simulated atmospheres ± noise, climate change, exercise, … The use of simulation chambers in a biological context constitutes a major innovative aspect of our project, as no such experimental set-up has been built before, and has therefore never been proposed in EU project focused on exposome. Risk assessment will be performed (multicriteria risk assessment and machine learning implementation), as well as economic evaluation (cost effectiveness and econometric modeling). Overall, the project should lead to new guidelines and recommendations regarding exposome/health effects. These could be beneficial to clinicians (to identify individuals at risk), researchers (to develop future treatments), and to public (to assess their personal risk, hopefully leading to changes of lifestyle). The production of several patents can be envisioned in the frame work of the project following the identification of new biomarkers and the development of sensors. To achieve our aim, the proposed network has a clear multidisciplinary dimension, as it brings together expertise of epidemiologists (Danish Cancer Society Research Center), adult and pediatrician lung specialists (CHI Créteil), physico-chemist of the atmosphere (LISA, FORTH), biologists (IMRB, Lipotype, Cambridge Epigenetix), engineer for sensor development (Fraunhofer), economics (Data Mining International), ethics and legal issues specialists (LN). The actual consortium will be completed with 2 other cohorts of patients (partners currently under discussion: ALSPAC, UK and RHINESSA, NO), and at least one partner for the dissemination of guidelines and recommendation (partner to be found).

Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are two very debilitating non-communicable diseases that are of particular interest to consider in parallel in a human exposome study. Their roots are opposite: COPD is currently considered to be mainly related to the external exposome, while factors outside of the exposome play a major role in CF. However, COPD and CF share common characteristics such as high phenotypic variability of unknown origin, which prevents good therapeutic efficacy. It is therefore clear that the overall picture must be supplemented by taking into account additional components of the exposome than those currently considered in COPD and CF. Thus, the overall objective of the REMEDIA project is to extend the understanding of the contribution of the exposome, taken as a complex set of different components, to COPD and CF diseases. We will exploit data from existing cohorts and population registries in order to create a unified global database gathering phenotype and exposome information; we will develop a flexible individual sensor device combining environmental and biomarker toolkits; and use a versatile atmospheric simulation chamber to simulate the health effects of complex exposomes. We will use machine learning supervised analyses and causal inference models to identify relevant risk factors; and econometric and cost-effectiveness models to assess the costs, performance and cost-effectiveness of a selection of prevention strategies. The results will be used to develop guidelines to better predict disease risks and constitute the elements of the REMEDIA toolbox (global unified database, sensor device, versatile atmospheric simulation chamber, machine learning supervised analyses, causal inference model, Pan-European multi-criteria risk assessment tool, econometric models, cost-effectiveness models, new guidelines and recommendations). Deciphering the impact of environmental components throughout life on the phenotypic variability of COPD and CF could represent a major breakthrough in reducing morbidity and mortality associated with these two non-curable diseases and would lead to the identification of modifiable risk factors on which preventive action could be implemented. REMEDIA will be part of the European Human Exposome Network established between the 9 projects funded within the Human Exposome programme call H2020-SC1-BHC-2018-2020.