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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease

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.

• Study Type: Observational
• Enrollment (Actual): 359

Contacts and Locations

Study Locations

• United States
  • California
    • Alhambra, California, United States, 91801
      • UCLA Research Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Medical School
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • New York
    • New York, New York, United States, 10032
      • Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Approximately Study Subjects:

MESA COPD will recruit approximately 360 participants from EMCAP at Columbia, and from MESA at Columbia; JH University; North Western University; and University of California.

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.

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cardiac structure and pulmonary vascular structure and function	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	Up to 2 years from start of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of CD31+/CD42 endothelial microparticles (EMPs)	Numbers of CD31+/CD42 EMPs reflective of apoptosis are elevated; They are abnormal in severe, moderate and mild COPD compared to controls.	Up to 2 years from the start of study
Number of circulating endothelial cells (CEC)	Numbers of circulating endothelial cells (CEC), resulting from endothelial injury, are elevated. They are abnormal in severe, moderate and mild COPD compared to controls	Up to 2 years from the start of study
Number of endothelial progenitor cells (EPCs), involved in endothelial repair, are decreased	They are abnormal in severe, moderate and mild COPD compared to controls.	Up to 2 years from the start of study

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: R. Graham Barr, MD, DrPh, Columbia University

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2009
• Primary Completion (Actual): April 30, 2018
• Study Completion (Actual): April 30, 2018

Study Registration Dates

• First Submitted: July 13, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimated): July 20, 2011

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 23, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: atherosclerosis; pulmonary hypertension; smokers; emphysema; Chronic Obstructive Pulmonary Disease (COPD); pulmonary vasculature
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: AAAD6395; R01HL093081-01 (U.S. NIH Grant/Contract)