Ambient Air Pollution Exposure and Mortality in the Pulmonary Hypertension Association Registry

Rationale: The effects of long-term ambient air pollution exposure on survival in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) remain unclear. Objectives: To evaluate the association between exposure to particulate matter with aerodynamic diameter ≤ 2.5 μm (PM_2.5), NO₂, and O₃ and mortality or lung transplant in the Pulmonary Hypertension Association Registry (PHAR). Methods: A total of 2,196 adult patients enrolled in the PHAR provided data between 2015 and 2024. Annual average concentrations of air pollutants, including PM_2.5, NO₂, and O₃, estimated from validated spatiotemporal models in 2015 were linked to each participant's residential address. Cox proportional hazards models evaluated the associations between air pollutant exposures and risk of death or lung transplant, adjusting for baseline demographics, individual and neighborhood socioeconomic factors, disease severity, and spatial confounders. Additional analyses were adjusted for and stratified by nine U.S. census divisions. Results: Study participants were broadly distributed across U.S. regions, with 72.0% female and a mean age of 55.7 years. A proportion of 35.6% had idiopathic PAH, 26.5% had connective tissue disease-associated PAH, and 14.5% had CTEPH. In models adjusted for demographics and individual and neighborhood socioeconomic factors, each interquartile range increase of PM_2.5 was associated with a mortality or lung transplant hazard ratio of 1.16 (95% confidence interval, 1.01-1.33). This association was marginally attenuated and not statistically significant after adjusting for spatial covariates, with a hazard ratio of 1.12 (95% confidence interval, 0.95-1.31) per interquartile range increase in PM_2.5. We noted regional variation in the observed associations. No significant associations were found with NO₂ or O₃. Conclusions: Long-term ambient air pollution exposure was not significantly associated with survival in PHAR patients with PAH or CTEPH. Future research should investigate potential modifying effects of regional social determinants and healthcare-related factors on the relationship between air pollution exposure and mortality in these conditions.