Chronic lower respiratory disease (CLRD) is currently the third leading cause of death in the United States. CLRD prevalence and mortality are increasing, particularly among women and minorities. Despite the magnitude of the problem, therapeutic options are limited. The most morbid components of CLRD are chronic obstructive pulmonary disease (COPD), which is defined by accelerated age-related loss in lung function, and emphysema, which is characterized accelerated loss of lung parenchyma and elasticity.
The understanding of the pathogenesis of COPD has moved beyond the protease-antiprotease hypothesis to include hypotheses relating to chronic inflammation and endothelial activation. The biological hypothesis that underlies the MESA Lung Study I was that alterations in endothelial and vascular function are associated with the pathogenesis and progression of subclinical COPD and emphysema, in part through the effects of systemic inflammation on the vascular endothelium. The MESA Lung Study II is testing hypothezes relating to heart-lung interactions in subclinical cardiopulmonary disease, one manifestation of which may be heart failure with preserved ejection fraction (HFpEF).
Multi-Ethnic Study of Atherosclerosis (MESA)
MESA is a prospective cohort study funded by the National Heart, Lung, Blood Institute (NHLBI) to investigate the prevalence, correlates and progression of subclinical cardiovascular disease in individuals without clinical cardiovascular disease. The MESA cohort consists of 6,814 men and women ages 45-84 years old, recruited from six U.S. communitie s: Forsyth County, NC; Northern Manhattan and the Bronx, NY; Baltimore City and Baltimore County, MD; St. Paul, MN; Chicago, IL; and Los Angeles, CA. MESA participants are non-Hispanic white, Hispanic, African-American, or Asian (of Chinese origin). Exclusion criteria included clinical cardiovascular disease (physician diagnosis of heart attack, stroke, TIA, heart failure, or angina), current atrial fibrillation, any cardiovascular procedure, pregnancy, active cancer treatment, weight >300 lbs, serious medical condition which precluded long term participation, nursing home residence, cognitive inability, inability to speak English, Spanish, Cantonese, or Mandarin, plan to leave the community within five years, and chest CT within the past year.
MESA participants were characterized during a baseline clinical visit in 2000-2002 with questionnaires, EKG, ankle-brachial index, cardiac CT and MRI scanning, carotid ultrasound, flow-mediated dilation (FMD) and arterial wave-form measures. Most measures were repeated on at least one of four follow-up visits through 2012. Additional details and protocols are available on the MESA website, www.mesa-nhlbi.org.
The MESA-Family Study is a family-based study that recruited over 1,800 African-Americans and Hispanics who were predominantly family members of MESA participants under the same inclusion criteria as MESA except that clinical cardiovascular disease was permitted. The MESA-Air Pollution Study recruited 257 participants at two sites under the same inclusion criteria as MESA.
MESA Lung Study (Investigator website)
The MESA Lung Study is an epidemiologic study funded by NHLBI initially to test endothelial hypothesis of COPD and emphysema, in addition to examining subclinical cardiopulmonary interactions. In 2004-06, the MESA Lung Study recruited 3,965 participants sampled randomly from MESA participants who had baseline FMD measures (89% of MESA), attended MESA Exam 3 or 4 (87% of MESA), and consented to genetic analyses (99% of MESA). Minority race/ethnic groups were oversampled; the MESA Lung cohort comprises approximately 35% non-Hispanic whites, 24% African-Americans, 23% Hispanics and 18% Chinese-Americans. Over 3,000 were re-examined in 2010-12.
All MESA-Lung participants were asked to partake in standardized spirometry testing performed by certified technicians following ATS/ERS guidelines using Sensormetics spirometers and OMI software 1 in 2004-06 and again in 2010-12. Post-bronchodilator spirometry was obtained on the second testing point.
MESA cardiac CT scans visualize approximately three-quarters of the lung volume. The MESA Lung Study assessed lung density measures (percent emphysema and ‘alpha' – slope of the log-log plot of hole size vs. cumulative distribution function) in the lung windows of all baseline and follow-up cardiac CT scans of MESA-Lung participants at the University of Iowa following a validated protocol. 2
The MESA Lung Study performed full-lung CT scans on six 64-slice MDCT scanners on over 3,000 participants in 2010-12 following the MESA Lung/SPIROMICS CT protocol.