EXPOSPAH

Context: pulmonary arterial hypertension (PAH) is a rare and incurable disease that can affect people of all ages. The disease is characterized by obstructive remodeling of the small pulmonary arteries, responsible for an increase in pulmonary arterial pressure, and leading to right heart failure and death in the absence of treatment. PAH can be associated with a variety of diseases but around half of all PAH is idiopathic or heritable and could develop as a result of a "second hit" as suggested by the identification of cases of PAH associated with the use of anorectic drugs, metamphetamine and occupational exposure to organic solvents. No study has yet systematically analyzed the exposome of PAH patients, associating environmental and occupational exposures as well as drugs, medications and socioeconomic data. Main objective: characterize the exposome at the time of diagnosis of PAH and assess its role in the development of PAH. Methodology: The project will consist of 2 stages designed to answer the question of the role of the exposome in PAH. The first stage will be a case-control study, to characterize the exposome at the time of PAH diagnosis in patients diagnosed in competence centers of the French PAH network, assessed using a combination of direct methods (mass spectrometry on hair and urine) and indirect methods (questionnaires and exposure matrices in collaboration with expert teams). The second stage will be an analysis of the effect of the environemental toxic substances identified in the first part of the study and in the literature, at the pulmonary endothelial cellular level and in animal models of PAH, in order to determine the mechanisms of pulmonary vascular toxicity of these toxic substances and their role in the pathophysiology of PAH. Perspectives: This project will provide better understanding of the role of the exposome in the development of PAH by identifying new causes of PAH among so-called "idiopathic" PAH and new mechanisms of PAH.