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Chronic obstructive pulmonary disease (COPD) is a respiratory disease affecting about 10% of adults above 40 years of age. COPD is caused by smoking, environmental exposure to pollutants or genetic factors, and results in difficulty of breathing. Chronic inflammation in COPD causes airway thickening, mucus overproduction and lung tissue degradation. It is the third highest cause of death in the United States. Additionally, an “exacerbation” of COPD, caused by an acute pulmonary infection, is associated with an accelerated decline in lung and physical function, and is the major healthcare burden of COPD. There is no cure for COPD. Pulmonary rehabilitation, a comprehensive intervention that includes exercise training, is one of the most effective treatments. Participation in pulmonary rehabilitation reduces exacerbation and hospitalization rates. We will investigate the cellular and molecular mechanisms underlying this association. Recent evidence from healthy individuals shows that exercise induces release of microscopic vesicles (termed “exosomes”) into the bloodstream, as well as reducing inflammation and exerting several health-related benefits. Yet, the effects of exercise on exosome release and chronic inflammation in COPD are not well known. This study will enroll 20 COPD patients and 20 controls to evaluate the effect of a moderate- and high-intensity 40-minute cycle-exercise workout on exosomes and immune cell gene and protein expression. In addition, 40 COPD patients will have exosomes and immune cell gene and protein expression evaluated before and after participation in a 12-week pulmonary rehabilitation program. We hypothesize that the COPD patients with the greatest increase in physical fitness following rehabilitation will experience the greatest changes in the characteristics of exosomes and inflammation. By determining the detailed networks of genes expressed and proteins synthesized following acute exercise and after training, we will identify how the immune cells themselves may be modulated, uncovering the pathways that reduce exacerbation frequency, severity and slow disease progression. Together, application of “high-throughput technologies” for comprehensive gene and protein expression analyses, combined with detailed clinical and physiological characterization, will uncover new mechanisms by which exercise benefits COPD patients. |
