Occupational and environmental exposures may drive sarcoidosis pathogenesis

SESSION TITLE: Diffuse Lung Disease Posters 7 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/11/2023 12:00 pm - 12:45 pm PURPOSE: The pathogenesis of sarcoidosis remains incompletely understood. Given the presence of noncaseating granulomas and inflammatory cells in involved tissues, glucocorticoid immunosuppressive therapy has remained the mainstay of treatment. Recent literature suggests that dysregulated autophagy, the complex cellular process by which cellular waste is recycled via lysosomal-regulated degradation, may play a key role in the development of sarcoidosis. Patients with sarcoidosis have been found to have mutations in autophagy genes. A "2-hit" hypothesis is proposed in the development of sarcoidosis: individuals with dysregulated cellular autophagy experience an occupational or environmental insult that is then ineffectively cleared, thus leading to a granulomatous response in affected tissues. This project aims to evaluate the incidence of occupational and/or environmental exposures in patients diagnosed with sarcoidosis at our institution. While such exposures are estimated to contribute to the development of disease in approximately 20% of patients with other chronic lung diseases, we posit that the contribution of occupational/environmental exposures is much higher in sarcoidosis. We postulated that patients with sarcoidosis have a clinically and statistically significant increase in occupational exposures compared to disease controls, thus supporting the hypothesis that particles/fibers from such exposures in the setting of dysregulated autophagy may drive granuloma formation and thus lead to sarcoidosis development. METHODS: Participants were at least 18 years old (adults), had a diagnosis of sarcoidosis, and actively received care through UNC Health. Seventy-two randomly selected patients who met inclusion criteria were identified and occupational and/or environmental exposures were investigated via chart review. Statistical analysis was performed comparing the difference in incidence of exposure history preceding a diagnosis of sarcoidosis when compared to the accepted attributable incidence in other chronic lung diseases such as asthma. RESULTS: Out of 72 patients with sarcoidosis evaluated, 41 (57%) were found to have a history of exposure to environmental insults including organic, metal, and synthetic dusts as well as chemical fumes. Specific exposures and occupations included burn pits, cotton mills, copper pipe factories, construction, large drums of printer dust, pottery/ceramics, automotive parts manufacturing, textile mills, water treatment plants, yarn factories, cutting granite, marble, brick, and terracotta pottery pipe. The incidence of occupational or environmental exposure history with potential particle/fiber exposure in patients diagnosed with sarcoidosis was significantly higher than the accepted attributable cause of other chronic lung diseases. CONCLUSIONS: The incidence of occupational or environmental exposure history in patients diagnosed with sarcoidosis was significantly higher than the accepted attributable cause of other chronic lung diseases. CLINICAL IMPLICATIONS: Increased exposure history in patients with sarcoidosis can support a dysregulated autophagy theory. Additionally, there is potential for greater investigation given the degree of disparity that exists within the patient population with sarcoidosis. With a greater understanding of the pathogenesis of sarcoidosis, improved and more selective treatment modalities can be investigated and developed, thus improving patient outcomes. DISCLOSURES: No relevant relationships by Andrew Ghio No relevant relationships by William Rathell Jr. No relevant relationships by Spencer Scott No relevant relationships by Stephen Tilley