Efficacy of interventions to alter measures of fat-free mass in people with COPD: a systematic review and meta-analysis

INTRODUCTION: Low fat-free mass (FFM) is linked to poor health outcomes in COPD, including impaired exercise tolerance and premature death. The aim of this systematic review was to synthesise evidence on the effectiveness of interventions for increasing FFM in COPD. METHODS: Searches of electronic databases (MEDLINE, Cochrane Library, Embase, Web of Science, Scopus) and trial registers (ClinicalTrials.gov) were undertaken from inception to August 2022 for randomised studies of interventions assessing measures of FFM in COPD. The primary outcome was change in FFM (including derivatives). Secondary outcomes were adverse events, compliance and attrition. RESULTS: 99 studies (n=5138 people with COPD) of 11 intervention components, used alone or in combination, were included. Exercise training increased mid-thigh cross-sectional area (k=3, standardised mean difference (SMD) 1.04, 95% CI 0.02–2.06; p=0.04), but not FFM (k=4, SMD 0.03, 95% CI −0.18–0.24; p=0.75). Nutritional supplementation significantly increased FFM index (k=11, SMD 0.31, 95% CI 0.13–0.50; p<0.001), but not FFM (k=19, SMD 0.16, 95% CI −0.06–0.39; p=0.16). Combined exercise training and nutritional supplementation increased measures related to FFM in 67% of studies. Anabolic steroids increased FFM (k=4, SMD 0.98, 95% CI 0.24–1.72; p=0.009). Neuromuscular electrical stimulation increased measures related to FFM in 50% of studies. No interventions were more at risk of serious adverse events, low compliance or attrition. DISCUSSION: Exercise training and nutritional supplementation were not effective in isolation to increase FFM, but were for localised muscle and index measures, respectively. Combined, exercise and nutritional supplementation shows promise as a strategy to increase FFM in COPD. Anabolic steroids are efficacious for increasing FFM in COPD.