HYPOTHESIS Multiplexed analysis of the diversity and targets of fungal exposome-induced sensitization enables risk modeling and long-term prediction, at the population and individual levels, of lung function, a correlate of longevity and quality of life. OBJECTIVES Main objective: To establish a biomarker pattern of multiplex sensitization to the environmental fungal exposome and allergic inflammation associated with lung function temporal trajectories in asthmatic and healthy adults from the French part of the ECRHS cohort (discovery cohort). The selected biomarkers will address allergic sensitization as revealed by specific antifungal antibodies of isotype E, hereafter denoted as immunoglobulin (Ig) E, using a custom multiplex allergen platform featuring all currently known allergenic fungal genera, and allergic inflammation based on eosinophil activation-related molecules. FUNGIPLEX involves and is coordinated by the French ECRHS clinical and scientific PIs: Pr P. Demoly (FUNGIPLEX coordinator and ECRHS clinical PI, Montpellier), Dr I. Pin (ECRHS clinical PI, Grenoble), Dr C. Neukirch (ECRHS clinical PI, Paris), Pr C. Raherison (ECRHS clinical PI, Bordeaux), Dr B. Leynaert (scientific coordinator of ECRHS France, Paris). FUNGIPLEX study design addressing the endpoint of allergic sensitization to environmental allergens is in compliance with ECRHS ethical and regulatory requirements. Secondary objectives: 1. To test the discovery cohort results in two distinct replication cohorts: a. Pediatric replication of adult findings: Replication in pediatric asthma. This replication arm will test the influence of age, assuming climate and genetic factors are comparable to ECRHS France. It will also add pathophysiological insight into the natural history of fungal sensitization during childhood. It will be performed with the French SAMP cohort comprising 424 preschool and school patients. Pr J. Just (Paris), the clinical PI of SAMP, is involved in FUNGIPLEX as scientific team leader. b. Swedish ECRHS replication of French ECRHS findings. This replication arm will test the influence of climate and genetic variation, assuming demographic and lung function characteristics are comparable to ECRHS France. ECRHS Sweden was designed and conducted similarly to ECRHS France. ECRHS Uppsala comprises 302 patients assessed at the 3 time points. FUNGIPLEX involves the clinical PIs of ECRHS Uppsala: Pr C. Janson and Pr A. Malinovschi. 2. To improve detection of susceptibility to long-term lung and health outcomes at the individual level: FUNGIPLEX will bridge mold exposure questionnaires with corresponding multiplex mold immune sensitization. ORIGINALITY A translational hub from epidemiological data to personalized medicine in the context of fungal exposome. EXPECTED RESULTS In terms of new knowledge, FUNGIPLEX will provide the description of the evolution of the fungal sensitization in relation to clinical outcomes at various times of life and taking different regions into account at the general population level. Of note, some of the fungi have never been considered in population studies. Determinants of this evolution will be investigated taking an EnvWAS approach into account. This information will be used for personal prevention. Clinically, FUNGIPLEX will provide an extensive fungal multiplex assay to be used in other cohorts (COBRA, EGEA, etc.) as well as in clinical routine. FINAL PRODUCT DEVELOPED The multiplex assay developed in the FUNGIPLEX study will help identify the most informative fungal allergens and serve as a basis for tailored multiplex tools. Such tools are needed for the extended or focused investigation of other fungal-related diseases involving IgE, IgG, or IgA in serum or local samples (nasal fluid, sputum), e. g. hypersensitivity pneumonitis, allergic bronchopulmonary mycoses and allergic fungal rhinosinusitis.