COPD is the third leading cause of death in the United States and has major public health impacts. Current treatments can improve symptoms but none prevent disease progression or reduce mortality. This is in part due to the high burden of comorbidities, including cardiovascular disease, which complicate diagnosis and treatment. COPD-associated cardiovascular disease has not been adequately studied but may provide avenues to improve clinical outcomes. There are currently no proven therapies for COPD-related pulmonary vascular disease despite numerous trials testing vasodilators in patients with severe pulmonary hypertension. Conduct of these studies has been hampered by the lack of a non-invasive measure of pulmonary pressure and no tools adequately detect early pulmonary vascular abnormalities. We have developed a novel, non- invasive, cardiac MRI measure of pulmonary artery impedance (the velocity transfer function) that may prove useful in the identification and quantification of COPD-associated pulmonary vascular disease.
Specific Aim 1 of this proposal is to determine whether the velocity transfer function can identify abnormalities in pulmonary arterial impedance in COPD and whether it correlates with right ventricular function. It is also well established that beta-blockers reduce mortality in patients with cardiovascular disease, but COPD patients are often denied these medications because of concerns about adverse effects of beta-blockade on airway function. Multiple observational studies now indicate that beta-blockers may in fact reduce exacerbation risk in COPD and the multicenter, randomized, placebo-controlled, Beta-Blocker for the Prevention of COPD Exacerbations (BLOCK- COPD) trial is underway to test this hypothesis. Regardless of the results, questions will remain about the risk- benefit of beta-blockers in patients with COPD, including their effects on exercise.
Specific Aim 2 of this proposal is to determine the effect of metoprolol on peak exercise as assessed by cycle ergometry in patients with COPD. This proposal also aims to provide mentoring and training opportunities to new investigators pursuing COPD Patient-Oriented Research (POR). Mentoring will be tailored to meet the interests and objectives of individual trainees but a core set of topics will be presented through one-on-one and group sessions. Specialized training in biostatistics as well as research applications of quantitative thoracic CT and cardiac MRI will also be provided. Trainees will also take advantage of career development programs offered by the UAB Center for Clinical and Translational Science. The proposal also aims to provide the PI with formal mentoring training as well as research training in comparative effectiveness and health services methodology which will open new avenues for his own investigative career as well as additional opportunities for trainees. The K24 will contribute significantly to the PI's long term career objectives to 1) extend our understanding of cardiopulmonary interactions in COPD; 2) conduct high impact POR to transform care for patients with the disease; and 3) help train the next generation of investigators planning careers in COPD POR.

Public Health Relevance

Chronic obstructive pulmonary disease (COPD) is now the third leading cause of death in the United States and co-morbid cardiovascular disease is a significant contributor to morbidity and mortality. This proposal seeks to develop a new tool to assess pulmonary vascular disease in COPD patients and to determine the impact of beta-blockers usually used to treat heart disease on exercise tolerance in this group. The project also aims to provide mentoring to young investigators pursuing careers in COPD Patient-Oriented Research and further research training to the PI.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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NHLBI Mentored Clinical and Basic Science Review Committee (MCBS)
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Lu, Qing
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University of Alabama Birmingham
Internal Medicine/Medicine
Schools of Medicine
United States
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