Oxidative stress, respiratory muscle dysfunction, and potential therapeutics in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a highly relevant disorder that induces respiratory muscle dysfunction. One prevalent symptom of COPD is resistive breathing which causes respiratory muscle to significantly increase the magnitude of contractions, resulting in reactive oxygen species (ROS) formation and oxidative stress. Through cellular signaling cascades, ROS activate molecules such as mitogen-activated protein kinases and nuclear factor-κB. These signaling molecules stimulate the release of cytokines which in turn cause damage to the diaphragm, involving sarcomeric disruptions. In response to COPD induced fatigue, the diaphragm undergoes a beneficial fiber-type shift to type I muscle fibers, which are more resistant to hypoxia than type II fibers. The lung hyperinflation that occurs in COPD also causes intercostal muscle dysfunction, thereby exacerbating COPD symptoms. In addition, COPD is known to have a connection with heart failure, diabetes, and aging, further decreasing respiratory function. Currently, there is no cure for this disorder. Nevertheless, various potential therapeutic strategies focusing on respiratory muscle have been identified including respiratory muscle training, β₂-agonist therapy, and lung volume reduction surgery. In this review, we will outline the role of COPD, oxidative stress, and related complications in respiratory muscle dysfunction.

Keywords

COPD / diaphragm / ROS / cytokine / respiratory therapy

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