D28-08 Air Pollution and Disease Severity in the Pulmonary Hypertension Association Registry

Rationale Long-term ambient air pollution has well-established health effects in cardiovascular and lung diseases, but limited evidence exists in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). We sought to evaluate cross-sectional associations between air pollutants, including fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), and pulmonary hemodynamics and morbidity among patients with PAH and CTEPH. Methods We studied adults enrolled between September 2015 and September 2025 in the Pulmonary Hypertension Association Registry, a multi-center prospective cohort of patients with PAH and CTEPH from across the United States (US). Previously validated spatiotemporal models for the contiguous US were used to estimate average PM2.5, NO2, and O3 concentrations in year 2015 at participants’ residential addresses. The dependent variables included baseline hemodynamics, six-minute walk distance (6MWD), brain natriuretic peptide z-scores, functional class (FC, binary outcome: class III-IV versus class I-II) and emPHasis-10, Short Form-12 (SF-12) scores. Multiple linear and logistic regression models were conducted with adjustment for demographics, individual- and neighborhood-level socioeconomic status, disease and treatment attributes, and spatial confounders. Repeated analyses were conducted using multiple imputation for missing covariates, and multipollutant models were fit to assess potential combined effects of co-exposures. Results The study sample included 3,371 adults with complete enrollment hemodynamics and residential addresses. 36.0% had idiopathic PAH, 24.5% connective tissue disease-associated PAH, and 15.8% CTEPH. The mean age was 56 years (standard deviation: 15.8 years) and 72.2% were female. Higher NO2 exposure was associated with higher pulmonary vascular resistance, with an increase of 0.33 [95% confidence interval (CI): 0.06 - 0.60] (p = 0.015) Wood units per interquartile range (IQR) increase in NO2 (4 ppb), and a decrease in Cardiac Index of -0.04 [95% CI: -0.08 - 0.00] (p = 0.048) L/min/m2 per IQR increase in NO2 (Figure 1). Higher PM2.5 was associated with shorter 6MWD (-9.0 [95% CI: -16.7 to -1.2] m per IQR increase in PM2.5 (2 µg/m3)), worse FC (odds ratio 1.16 [95% CI: 1.00 - 1.35]), and lower SF-12 mental component score (-0.80 [95% CI: -1.52 to -0.10]). Results were similar in sensitivity analyses imputing missing covariates and multipollutant models. Conclusion Long-term ambient air pollution was significantly associated with small differences in pulmonary hemodynamics, six-minute walk distance, functional class, and health-related quality of life in patients with PAH and CTEPH. The clinical implications of pollutants on measures of severity in PAH are still unclear, underscoring the need for further longitudinal studies. This abstract is funded by: NHLBI (National Heart, Lung, and Blood Institute)