The Role of Residential Bioaerosol Exposure in Pulmonary Sarcoidosis

Summary/Abstract Sarcoidosis a rare systemic inflammatory disease with high morbidity and increasing mortality. Granulomatous inflammation affects the lungs in 90% of cases, with ~1/3 of patients progressing to experience severe pulmonary disease that can result in lung transplant or death. Sarcoidosis is thought

to be due to interaction between an unknown environmental antigen and host genetic susceptibility. Extensive epidemiological evidence supports the involvement of bioaerosol in pulmonary sarcoidosis. However, only one component of bioaerosol has been directly measured in a cohort of patients with sarcoidosis. We hypothesize residential bioaerosol exposure drives immune dysregulation in pulmonary

sarcoidosis leading to severe lung disease. We will test this through three aims: Specific Aim 1: Determine the association between rBio and pulmonary sarcoidosis severity. We hypothesize bioaerosol exposures are unique within residences of those experiencing severe pulmonary sarcoidosis compared to exposures of patients with minimal to non-existent fibrosis and

controls. We will collect rBio and analyze its composition using traditional and micro/mycobiome techniques, then compare it to patient symptoms, lung function and chest imaging. Specific Aim 2: Determine the role of rBio in peripheral blood immune dysregulation in fibrotic pulmonary sarcoidosis. We will quantify and compare serum biomarkers and immune cell profile to

rBio. We will compare these findings to controls, and to patient pulmonary disease severity using patient symptoms, lung function, and chest imaging. Specific Aim 3: Assess the epithelial responses to rBio in severe pulmonary sarcoidosis. We hypothesize epithelial cells from patients with fibrotic pulmonary sarcoidosis will have impaired cell

adhesion, and barrier integrity in response to rBio. We will test this hypothesis in vitro by exposing primary human airway epithelial cells from recruited subjects to BDG, LPS and mixed bioaerosol from residences. We will assess protein expression, transcriptomic and functional responses. Completion of this proposal will inform potential disease mechanisms, diagnostic and progression

biomarkers, and novel treatments for people with sarcoidosis including environmental remediation