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

The Multi-Ethnic Study of Atherosclerosis (MESA) - Chronic Obstructive Pulmonary Disease (COPD) Study aims to characterize the pulmonary vascular changes and their biology in early COPD using imaging, gene expression profiling and peripheral cellular measures.

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.

Approximately 125 participants will be recruited from EMCAP at Columbia, and approximately 200 participants will be recruited from MESA (50 at Columbia; 50 at John Hopkins University; 50 at North Western University; and 50 at University of California University).

Cases will be defined according to the current American Thoracic Society/European Respiratory Society (ATS/ERS) definition of COPD of a post-bronchodilator capacity (FEV1/FVC) ratio < 0.70 and classified as mild, moderate and severe as post-bronchodilator FEV1 of 80-100% predicted, 50-80% predicted and < 50% predicted, respectively.

Controls will be defined in the above sampling frame as those with normal lung function (pre-bronchodilator FEV1/FVC ratio >= 0.70, and no restrictive ventilatory defect [COPD cases do not have a restrictive ventilatory defect by definition]).

Inclusion Criteria:

• age 50-75 years at time of enrollment
• ever smokers (10 or more packyears)
• participation in MESA or EMCAP studies

Exclusion Criteria:

• clinical cardiovascular disease (left congestive heart failure (CHF), valve disease, coronary artery disease (CAD), stroke, or congenital heart disease),
• asthma, pulmonary embolism or lung disease other than COPD,
• weight > 300 lbs,
• chronic renal insufficiency ([eGFR] < 60 mL/min/1.73 m2),
• cancer,
• atrial fibrillation, and
• contraindications to magnetic resonance imagine (MRI), gadolinium, albuterol or spirometry testing.