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Oxidative stress and skeletal muscle dysfunction in COPD

Institution: University of California, San Diego
Investigator(s): Russell Richardson, Ph.D. Michael Hogan, Ph.D.
Award Cycle: 2006 (Cycle 15) Grant #: 15RT-0100H Award: $569,914
Subject Area: Pulmonary Disease
Award Type: Research Project Awards

Initial Award Abstract
It is now well established that smoking results can cause a disease known as chronic obstructive pulmonary disease (COPD). This disease causes many problems throughout the body, including the lungs, skeletal muscle, the heart, and the blood vessels. Problems in the skeletal muscle (called “muscle dysfunction”) of patients with COPD are so severe that they are often unable to perform any physical activity, so that the activities of daily life become very difficult, and the quality of life declines. One possible cause of this muscle dysfunction in COPD patients may be an increase in “free radicals” in the body, highly reactive molecules which are known to cause damage to many parts of the body when present in large amounts. The body naturally produces antioxidants, which naturally defend against free radicals and therefore control the amount of “oxidative stress” in the body. However, in diseases such as COPD, oxidative stress may rise to the point that the muscle and blood vessels no longer function normally. As far as we know, no experiments have been performed to directly measure free radicals or to determine the level of oxidative stress in COPD patients. Thus, we have proposed a set of experiments in COPD patients which will ask three questions: Where is oxidative stress most prevalent, why does oxidative stress occur, and what are the consequences of oxidative stress? Experiments will be performed at rest and during exercise using novel techniques which can directly measure free radicals in the blood and muscle. Patients will also take antioxidant pills to determine if this simple treatment can lower the amount of free radicals in the muscle and blood, and thus reduce oxidative stress. These proposed studies may help to identify oxidative stress as an important contributor to the progression of COPD, as well as provide a possible way to treat the skeletal muscle dysfunction seen with this disease. If skeletal muscle function can be improved in these patients, the capacity for physical activity may also increase, and therefore findings from these studies could ultimately lead to an improved quality of life for COPD patients.