In this cross-sectional cohort analysis from the MESA COPD Study, platelet activation markers were associated with features of small airway disease and altered pulmonary microvascular perfusion in current and former smokers. These findings suggest a potential role of platelet activation in chronic obstructive pulmonary disease (COPD) pathophysiology.
The study enrolled smokers with at least 10 pack-years of exposure, with and without COPD, from two existing cohorts. Platelet activation was measured using plasma levels of von Willebrand factor (vWF), beta-thromboglobulin (BTG), and platelet factor 4 (PF4). Participants underwent detailed phenotyping using spirometry, chest computed tomography (CT), helium-3 magnetic resonance imaging (³He-MRI), and contrast-enhanced MRI for pulmonary perfusion. Multivariable regression models were adjusted for demographic and clinical variables, including smoking status, oxygen saturation, and hypertension.
Among the 116 participants with vWF data, the mean age was 73.5 ± 7.3 years; 60% were male, 58% Non-Hispanic White, 28% Black, and 14% Hispanic/Latino. Current smokers made up 23% of the group, and 55% had COPD. vWF levels were significantly associated with reduced forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC) by -2.0% per standard deviation increase in vWF (95% CI: -3.5, -0.6). vWF was also associated with greater percent low-ventilated lung volume on ³He-MRI (6.5% per SD, 95% CI: 1.5, 11.5), increased air trapping on CT (3.2% per SD, 95% CI: 1.4, 5.1), and increased heterogeneity of pulmonary microvascular blood flow and volume on oxygen. Higher levels of BTG and PF4 were linked to increased pulmonary microvascular blood flow (PMBF) and blood volume (PMBV). In the final adjusted model, higher PF4 levels were associated with increased odds of COPD (odds ratio 1.8 per SD PF4; 95% CI: 1.01, 3.20).
This study highlights that platelet activation markers are associated with physiologic and imaging features of small airway dysfunction and pulmonary vascular changes. These findings may offer insight into inflammatory and vascular mechanisms contributing to COPD in smokers.
