Loss of skeletal muscle oxidative phenotype and endurance in mild‐to‐moderate COPD

Abstract

Loss of skeletal muscle oxidative phenotype (OXPHEN) and subsequent impaired muscle endurance are hallmarks of severe COPD, but less is known regarding these in mild‐to‐moderate COPD. We studied muscle OXPHEN in relation to muscle endurance in mild‐to‐moderate COPD patients (mean FEV1 58±16 %pred). Quadriceps biopsies were collected from 29 clinically stable mild‐to‐ moderate COPD patients and 15 controls to analyze fiber type distribution and gene expression levels of oxidative and glycolytic markers. Quadriceps strength and fatigability were determined by peak torque and temporal decline in torque respectively, during 30 maximal voluntary isokinetic leg extensions. Compared to controls, COPD patients had significantly lower fiber type I proportions, oxidative PGC1α and MyHC I mRNA levels, and higher glycolytic PFKM expression. Muscle strength was not different, but endurance was reduced in COPD and correlated with gene expression of PGC1α and MyHC I. A trend was observed with % type I fibers. No markers correlated with FEV1. To our knowledge this is the first time that loss of muscle OXPHEN associated with impaired muscle endurance is observed in patients with mild‐to‐moderate COPD. This supports the indication for and efficacy of lifestyle intervention targeting muscle function in less advanced COPD as previously proven in a RCT (Van Wetering et al. Thorax 2010). Performed within TI Pharma T1‐201.