Pulmonary Vascular Changes in Early Chronic Obstructive Pulmonary

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.

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.