Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease (COPD), pulmonary vasculature, pulmonary hypertension, atherosclerosis, smokers, emphysema
Brief summary
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.
Detailed description
Chronic Obstructive Pulmonary Disease (COPD) is the third 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 longitudinal study of smokers nested among the MESA-Lung (AAAA7791) and EMphysema and Cancer Action Project (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 longitudinal study of smokers nested within the MESA-Lung and EMCAP cohorts of 360 participants (160 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.
Interventions
None listed
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Columbia University
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* age 50-79 years at time of enrollment * ever smokers (10 or more pack-years) * 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 (\[estimated glomerular filtration rate (eGFR)\] \< 45 mL/min/1.73 m2), * atrial fibrillation, and * contraindications to magnetic resonance imagine (MRI), gadolinium, albuterol or spirometry testing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cardiac structure and pulmonary vascular structure and function | Up to 2 years from start of study | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of CD31+/CD42 endothelial microparticles (EMPs) | Up to 2 years from the start of study | Numbers of CD31+/CD42 EMPs reflective of apoptosis are elevated; They are abnormal in severe, moderate and mild COPD compared to controls. |
| Number of circulating endothelial cells (CEC) | Up to 2 years from the start of study | Numbers of circulating endothelial cells (CEC), resulting from endothelial injury, are elevated. They are abnormal in severe, moderate and mild COPD compared to controls |
| Number of endothelial progenitor cells (EPCs), involved in endothelial repair, are decreased | Up to 2 years from the start of study | They are abnormal in severe, moderate and mild COPD compared to controls. |
Countries
United States
Outcome results
None listed