COPD elicits remodeling of the diaphragm and vastus lateralis muscles in humans

Abstract

A profound remodeling of the diaphragm and vastus lateralis (VL) occurs in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). In this mini-review, we discuss the following costal diaphragm remodeling features noted in patients with moderate-to-severe COPD: 1) deletion of serial sarcomeres, 2) increased proportion of slow-twitch fibers, 3) fast-to-slow isoform shift in sarco(endo)plasmic reticulum Ca2+-ATPase, 4) increased capacity of oxidative metabolism, 5) oxidative stress, and 6) myofiber atrophy. We then present the sole feature of diaphragm remodeling noted in mild-to-moderate COPD under the heading “ MyHC and contractile remodeling noted in mild-to-moderate COPD.” The importance of VL remodeling in COPD patients as a prognostic indicator as well as a major determinant of the ability to carry out activities of daily living is well accepted. We present the remodeling of the VL noted in COPD patients under the following headings: 1) Decrease in proportion of slow-twitch fibers, 2) Decreased activity of oxidative pathways, 3) Oxidative and nitrosative stress, and 4) Myofiber atrophy. For each of the remodeling features noted in both the VL and costal diaphragm of COPD patients, we present mechanisms that are currently thought to mediate these changes as well as the pathophysiology of each remodeling feature. We hope that our mechanistic presentation stimulates research in this area that focuses on improving the ability of COPD patients to carry out increased activities of daily living.