Pulmonary Vascular Changes in Early Chronic Obstructive Pulmonary (MESA-COPD)

• Changes in cardiac structure and pulmonary vascular structure and function [ Time Frame: Up to 2 years from start of study ] [ Designated as safety issue: No ]

  Cardiac structure: changes in right ventricular (RV) mass, RV mass/Right Ventricular End-Diastolic Volume (RV-EDV)

  Pulmonary structure: changes in total pulmonary vascular volume (TPVV) and pulmonary artery (PA) perfusion

  Function: changes in PA flow and distensibility

  
  

• Measure of Endothelial microparticles (EMPs) [ Time Frame: Up to 2 years from the start of study ] [ Designated as safety issue: No ]

  Circulating EMPs and cells are abnormal in severe, moderate and mild COPD compared to controls. In cases:

  1. Numbers of CD31+/CD42 EMPs reflective of apoptosis are elevated;
  2. Numbers of circulating endothelial cells (CEC), resulting from endothelial injury, are elevated;
  3. Numbers of EPCs, involved in endothelial repair, are decreased
  
  

Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death in the US and will soon replace stroke as the third leading cause.

Translation of promising biological hypotheses of COPD pathogenesis to human populations that may lead to new therapies is urgently needed. The vascular hypothesis of COPD was articulated almost 50 years ago. Bench research on endothelial dysfunction in COPD is evolving rapidly and has shown that acrolein in cigarette smoke causes endothelial apoptosis and endothelial apoptosis is directly implicated in COPD pathogenesis. Clinical studies on endothelial dysfunction and vascular changes in COPD are limited.

The proposed study is a cross-sectional study of smokers nested among the MESA-Lung (AAAA7791) and EMCAP Studies (AAAA6484), which together provide a well-defined cohort of 4,617 participants with prior spirometry and CT measures.

The Multiethnic Study of Atherosclerosis - Chronic Obstructive Pulmonary Disease (MESA COPD Study) has two main scientific purposes:

1. characterize the pulmonary vascular changes in COPD and their biology, and
2. propose novel pathways for new therapies in COPD.

MESA COPD is a cross-sectional study of smokers nested within the MESA-Lung and EMCAP cohorts of 325 participants (125 cases with mild, 60 cases with moderate and 40 cases with severe COPD and 100 controls) who will be phenotyped with magnetic resonance (MR) pulmonary angiography, pulmonary function testing, full-lung CT scans, serum Vascular Endothelial Growth Factor (VEGF), cell assays and gene expression profiling. MESA COPD Study will contribute improving the knowledge of early changes in COPD that may lead to novel disease-modifying medical therapies and preventative strategies.