D13-02 The Association Between Long-Term Air Pollutant Exposures and Pulmonary Vascular Pruning Among Tobacco-Exposed Individuals With COPD: A Spiromics Analysis

Rationale Limited data exists regarding the effect of air pollutants on pulmonary vasculature. Pruning of the pulmonary vasculature can be quantified by the ratio of total blood volume of vessels with cross-sectional area <5mm2 to total pulmonary blood volume (BV5/TBV), with lower BV5/TBV indicating increased pruning. We investigated the relationship between BV5/TBV and 10-year mean ambient air pollutant exposures among SPIROMICS participants (≥ 20 pack-year smoking history). Methods The SPIROMICS Air Pollution study modeled mean outdoor concentrations of fine particulate matter (PM2.5), nitric dioxide gas (NO2), and ozone gas (O3) in the 10 years preceding the SPIROMICS baseline visit. Air pollutant concentrations were estimated using a hierarchical high-resolution spatiotemporal model trained on regulatory and cohort-specific monitoring data, incorporating geographic variables based on residential addresses. BV5/TBV was measured using inspiratory CT scans completed at the baseline visit. Using linear models, we examined the association between 10-year average PM2.5, NO2, and O3 exposures and BV5/TBV. We stratified analyses by GOLD classification of spirometry airflow obstruction: none (GOLD 0), mild-moderate (GOLD 1-2), and severe (GOLD 3-4). Adjustment covariates included age, sex, height, weight, current smoking status, smoking pack-years, CT manufacturer, and study site. Results We analyzed 2,076 participants aged 40-80 years: GOLD 0 (n = 722), GOLD 1-2 (n = 932), and GOLD 3-4 (n = 422). Median and interquartile range (IQR) values of pollutant exposure for the cohort were: PM2.5 10.86 (3.49) µg/m³; NO2 13.53 (10.49) ppb; and O3 25.11 (6.29) ppb. No significant relationships were found between PM2.5, NO2, or O3 exposures and BV5/TBV in in GOLD 0 or GOLD 1-2 participants. However, in GOLD 3-4 participants, each IQR unit concentration increase in NO2 was associated with lower BV5/TBV (-1.16%, 95% CI -2.06, -0.26). When all three pollutants were included in the same model for GOLD 3-4 participants, a lower BV5/TBV was associated with IQR unit increases in exposures to both NO2 (-3.52%, 95% CI -4.97, -2.06, p < 0.001) and O3 (-2.42%, 95% CI -3.64, -1.20, p = 0.001), but not with PM2.5 (0.06%, 95% CI -1.10, 1.23, p = 0.90). Conclusion This analysis of centers across the United States demonstrates significant associations between 10-year NO2 and O3 exposures and CT-measured vascular pruning in individuals with severe COPD, independent of current or previous smoking. These data suggest that long-term gas pollutants may contribute to vascular remodeling or endothelial damage in patients with obstructive lung disease.