Effect of High Altitude on Small Pulmonary Vein and Artery Volume in the COPDGene Cohort: Towards Better Understanding of Lung Physiology and Pulmonary Disease

<b>Background:</b> To personalize the care for persons with smoking-related lung disease, a thorough understanding of its etiology is essential. The role of pulmonary vessels remains poorly understood. Living at high altitude provides a natural model to investigate the effects of low oxygen levels on pulmonary vessels. This study aims to evaluate the relationship between living at high altitudes and small pulmonary vein and artery volumes. We hypothesize that small vein and artery volumes were independently associated with living at high altitude. <b>Methods:</b> We quantified small pulmonary vein and artery dimensions (ᴓ < 1 mm) on computed tomography (CT) down to 0.2 mm in diameter and normalized the dimensions by body surface area. In 8931 current and former smokers participating in the COPDGene study, we used multivariate regression models corrected for clinical and technical confounders. <b>Results:</b> 1262 residents (14.1%) were defined as high-altitude residents (~1600 m, Denver, CO, USA). Compared to lower-altitude residents, the high-altitude residents had a higher age (62.0 ± 9.1 vs. 59.6 ± 9.0 years), more pack-years smoked (46.8 vs. 44.1) and a lower FEV₁% predicted (64.6 ± 32.4% vs. 76.8 ± 25.2%). Both mean small artery volume (4.09 ± 0.89 mL/m² vs. 3.85 ± 0.90 mL/m²) and mean small vein volume (2.96 ± 0.53 mL/m² vs. 2.67 ± 0.53 mL/m²) were higher in high-altitude residents. Multivariate linear regression showed that, in those without COPD, high-altitude residents have a higher small vein volume (0.129 mL/m², <i>p</i> < 0.001) and higher small artery volume (0.170 mL/m², <i>p</i> = 0.001) compared to lower-altitude residents. There was no significant association in residents with COPD. <b>Conclusions:</b> In current and former smokers without COPD, higher small pulmonary vein and artery volumes were associated with living at high altitude, independent of lung disease or technical CT parameters. A potential cause includes vascular remodeling due to an elevated need for blood oxygen transport, which becomes concealed when COPD develops.