Understanding Pulmonary Fibrosis Through the Integration of Complex Occupational and Environmental Exposure Assessments (PF-OEM)

Statement of the Problem: Pulmonary fibrosis (PF) is a chronic lung disease characterized by tissue scarring and is common in interstitial lung diseases (ILDs). ILDs contribute significantly to global mortality and healthcare expenses. Some ILDs are considered idiopathic, but research indicates that exposure to inhalants like vapors, gases, dust, and fumes at work or in the environment can promote fibrosis and inflammation, leading to PF. Most research focuses on treatments and comorbidities, neglecting the impact of preventable occupational and environmental exposures. Additionally, marginalized communities with higher exposure rates are rarely studied. Investigating inhalational exposures can help shape environmental policies and workplace safety, preventing PF in affected communities and vulnerable workers. Specific Aims: I aim to use epidemiologic tools to assess the occupational and environmental risk factors and progression of fibrotic ILD, analyzing a large dataset, the California Electronic Death Registration System (Cal- EDRS), and an ongoing prospective cohort, the University of California San Francisco UCSF ILD Cohort Study. In Aim 1, I plan to systematically develop a new PF-specific job-exposure-matrix (PF-JEM) and measure the association between occupational exposure and PF in the Cal-EDRS. In Aim 2, I will assess the interaction of environmental and occupational exposures on the occurrence of PF in the Cal-EDRS, using air pollution data from the CalEnviroScreen and geospatial techniques. To achieve Aims 1 and 2, I will utilize a case-control study design in the Cal-EDRS to measure the association between occupational and environmental exposures using multiple predictor models and stratified analysis. Finally, in Aim 3, I will evaluate the interaction of environmental and occupational exposures on clinical outcomes of IPF in the UCSF ILD Cohort Study, including survival, using multivariable Cox proportional hazards analysis with stratification. Significance of the results. The Cal-EDRS and the UCSF ILD Cohort Study offer a unique opportunity to study the interplay of occupational and environmental exposures on PF utilizing state-of-the-art exposure assessment techniques of a JEM and residential address geocoding. This study is innovative through its linkage of a novel PF-JEM to both a rich dataset of vital statistics records and an ongoing cohort study to investigate the risks and clinical patient outcomes of PF due to inhalational exposures. Career Development: With the above proposal, Dr. Gandhi will achieve her training goals of 1) Epidemiologic occupational exposure assessment, 2) Advanced environmental exposure assessment using geospatial techniques, and 3) Survival analysis and clinical outcomes assessment of exposed patients with ILD. The K23 award will facilitate her transition to independence as a physician-scientist who utilizes innovative epidemiological methods and exposure metrics to develop a research program focusing on clinical outcomes of patients with occupational and environmental lung disease. Project Number: 1K23HL173628-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Sheiphali Gandhi | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $190,998 | Activity Code: K23 | Study Section: NHLBI Mentored Patient-Oriented Research Study Section[MPOR (JA)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1K23HL17362801A1