PROJECT SUMMARY The Clinical and Biospecimen Core (Core A) will support each Project in the Program by implementing all proposed studies involving human research participants. The long-term goal of the Program is to identify new strategies to prevent pulmonary fibrosis (PF) by advancing understand of the pathobiological cascade that initiates progressive PF. The Program is focused on the pre-symptomatic period, which represents the ideal time for therapeutic interventions to modify the course of PF. Using state-of-the-art single-cell and spatial transcriptomic approaches, biomarker analysis, and environmental exposure assessment, the Projects will elucidate critical factors that underlie early disease pathogenesis. Dr. Salisbury, Dr. Blackwell, and other Core personnel have established a reputation as leaders in PF research, including conduct of investigator-initiated clinical trials and observational studies. The Familial Pulmonary Fibrosis (FPF) Registry is an observational study maintained by Core personnel that has been a key resource to identify asymptomatic members of FPF families who are at risk to develop FPF. The At-Risk for FPF Cohort, the backbone of this Program, was incepted in 2008 and directed by Dr. Salisbury since 2019. The At-Risk Cohort has already recruited 489 research volunteers, who are asymptomatic relatives of patients with FPF, to undergo serial screening for pre- clinical PF with high-resolution chest CTs (HRCTs), pulmonary function tests, and blood donation. The Specific Aims for Core A are to: 1) Recruit research participants and perform all clinical procedures; 2) Coordinate clinical studies, collect, maintain, and distribute data collected from human research subjects, and maintain regulatory requirements; and 3) Process, catalog, and distribute biological specimens collected from human research subjects. Key At-Risk Cohort sub-studies implemented by the Core include the Lung Sampling (Bronchoscopy) in Pre-Clinical FPF Sub-Study, in which a total of 40 additional At-Risk Cohort participants will undergo lung sampling via a research bronchoscopy with bronchoalveolar lavage (BAL), bronchial brushing (for airway epithelial cell collection), and transbronchial lung biopsies, and the Exposures in Pre-Clinical FPF Sub-Study, in which up to 300 At-Risk Cohort participants will undergo a detailed environmental exposure assessment with prospective sampling to measure potentially harmful exposures. Core A supports the Program’s goals by maintaining the At-Risk for FPF Cohort, identifying those with pre-clinical (pre- symptomatic) PF, implementing key sub-studies, and providing each Project with the necessary samples and data.