The Clinical Impact of Pulmonary Vascular Remodeling in Smokers

Smoking related pulmonary vascular disease has been demonstrated to be an independent predictor of morbidity and mortality in patients with COPD. Previous investigation and observation suggests that there are several types of pathologic pulmonary vascular remodeling possible in smokers. These range from inflammatory remodeling with progressive luminal occlusion, aberrant vessel elongation in regions of hyperinflation, and outright loss of vasculature in regions of severe emphysematous destruction. While there are existing tools that may be used to investigate the aggregate effect of these processes such as right heart catheterization, echocardiography, and measurements of diffusing capacity for carbon monoxide (DLCO), none can differentiate the types of vascular remodeling/deformation present nor their relative contribution to clinical impairment. The purpose of this investigation is to improve understanding of the clinical impact and epidemiologic associations of pulmonary vascular remodeling in smokers. We will do this by performing CT based quantitative measures of the mediastinal (Aim 1) and intra-parenchymal vasculature (Aim 2) in all subjects enrolled in the COPDGene Study and then clinically validating these measures with echocardiography, cardiac MRI and measures of DLCO (Aim 3). In the final steps of Aim 3 we will examine the overlap and associations between pulmonary and cardiovascular disease (both clinical diagnosed CVD and both coronary and thoracic aortic calcification) and the relationship between pulmonary vascular morphology and exercise capacity, acute exacerbations of COPD, symptoms, and mortality. We believe that this will lead to improved understanding of the pathophysiology of COPD and may ultimately improve the care of patients with COPD.