Pulmonary vascular changes are thought to occur late in COPD, secondary to severe hypoxemia and acidosis. Bench research, however, has shown endothelial cell dysfunction and vascular endothelial growth factor (VEGF)-mediated apoptosis in early COPD. These observations have revived the “vascular hypothesis” of COPD, which posits that alterations in the pulmonary vasculature lead to loss of lung function.

The MESA COPD Study is a study of smokers nested among these two cohorts, which together provide a well-defined sampling frame of 4,617 participants with prior spirometry and CT measures. A total of 325 participants were characterized with MRI and full-lung CT imaging, spirometry, flow cytometry, and gene expression profiling to test the following hypotheses:

1) Functional and structural changes in the pulmonary vasculature and right ventricle assessed with novel CT and MRI measures occur early in COPD;

2) Endothelial microparticles, circulating endothelial cells, and endothelial progenitor cells are abnormal early in COPD;

3) Plasma VEGF levels and gene expression of apoptotic and nitrogen oxide metabolism pathways in peripheral blood mononucleated cells (PBMCs) are altered early in COPD.