Low Oxidative Capacity in Skeletal Muscle of Both the Upper and Lower Limbs in COPD Patients
Authors: Adami Alessandra , Corvino Rogerio B. , Casaburi Richard , Cao Robert , Calmelat Robert , Porszasz Janos , Rossiter Harry B. 
Published: November 2023

Chronic obstructive pulmonary disease (COPD) is associated with a progressive loss of muscle mass and endurance, together with a loss of mitochondrial oxidative capacity, mitochondrial dysfunction and capillary rarefaction in the peripheral muscles. Leg muscle dysfunction exacerbates dyspnea, contributes to exercise intolerance and morbidity. The mechanisms leading to leg muscle dysfunction are debated, with both deconditioning and intrinsic (circulating) factors proposed to contribute. Comparison of upper and lower limb performance in COPD, proposed to reveal relative influence of behavioral and disease‐related factors, show conflicting results: Franssen et al. (MSSE 37:2–9, 2005) reported preserved biceps brachii endurance compared with the quadriceps, while Miranda et al. (Respiratory Care 59:62–9, 2014) found decreased endurance and greater fatigability in the upper limbs. We therefore aimed to determine whether loss of muscle oxidative capacity was different between the upper and lower limbs in COPD patients and also in smokers with normal spirometry.Twenty COPD patients (GOLD 2/3/4, n=7/7/6; FEV1%pred 46.5±3.39; M/F=15/5; age 64±9yrs; body weight 73±17kg; height 1.72±0.1m) and 20 current or former smokers with normal spirometry (CON; M/F=15/5; age 63±7yrs; body weight 77±15kg; height 1.69±0.1m) volunteered. Oxidative capacity of the non‐dominant medial forearm and medial gastrocnemius was measured using near‐infrared spectroscopy. After a 10–15s of brief forearm/thigh muscle contractions, the muscle O2 consumption recovery rate constant (k, min−1) was determined using repeated intermittent arterial occlusions. k was estimated from the mean of two repetitions in each limb on a single study visit. 2‐way ANOVA (group × limb) was used to assess potential differences.One COPD patient and 1 control could not tolerate the arterial occlusions required for the assessment, and were excluded from the study. There was a significant main effect of group on muscle oxidative capacity (F=11.2, ηp2=0.13, p=0.001): COPD patients had significantly lower k in both upper and lower limb muscles (upper 1.01±0.17, lower 1.05±0.24 min−1) compared with CON (1.25±0.49, 1.49±0.65 min−1). However, there was no effect of limb (F=1.8, ηp2=0.02, p=0.18) and no group × limb interaction (p=0.35).COPD patients showed a lower muscle oxidative capacity than controls in the skeletal muscles of both upper and lower limbs. Compared with age‐ and sex‐matched smokers with normal spirometry, k tended to be reduced by a greater extent in the gastrocnemius (−30%) than the forearm (−20%) of COPD patients; however, this difference was not significant (p=0.06). These data suggest that muscle oxidative capacity is systemically impaired in COPD patients, and not simply a consequence of inactivity‐induced muscular deconditioning; this latter would be expected to be manifest as greater impairments in the lower limb muscles compared to the upper limb. The systemic variables contributing to deficiency in muscle oxidative capacity in COPD warrant further study.Support or Funding InformationSupported by SNSF P300PB_167767; PERF; ATS Foundation/Breathe California of Los Angeles