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

Abstract

IntroductionLow 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.MethodsSearches 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.Results99 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, 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.DiscussionExercise 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.

ERS International Congress 2023: highlights from the Respiratory Clinical Care and Physiology Assembly

“…Another meta-analysis (99 studies; 5138 patients) examining interventions to increase fat-free mass in COPD emphasised that exercise-induced increases in fat-free mass are localised to the trained region (not whole-body), and highlighted potential benefits of nutritional supplementation and anabolic steroids in addition to exercise to maximise benefit [ 49 ]. Future research in this area should consider a personalised medicine approach to tailor interventions for individuals.…”

Gaining muscle mass in COPD: a work in progress

“…A systematic review and meta-analysis in ERJ Open Research by J enkins et al . [ 5 ] summarised the current evidence around treatments for low muscle mass in this population. The review identified three main intervention strategies that have been investigated for their potential to improve muscle mass in COPD as exercise (including resistance) training, nutritional supplementation and anabolic steroids.…”

“…These drug studies and the review J enkins et al . [ 5 ] highlight important considerations for research into therapies to (re)build muscle mass among patients with COPD or other chronic diseases. First, the choice of participant group needs careful consideration; not all patients with COPD have muscle wasting and it does not always translate to a clinically relevant consequence.…”

“…J enkins et al . [ 5 ] note that subanalyses of studies assessing the effect of anabolic steroids among “depleted” versus “non-depleted” COPD patients suggest a clear divergence in effects, with greatest benefit among those who were malnourished, underweight or sarcopenic. The inconsistency in such assessment and definition of low muscle mass across the literature is problematic and inhibits like-for-like comparison.…”

“…A key finding from the review by J enkins et al . [ 5 ] was the observation that combining interventions such as nutritional supplementation with exercise showed promise towards an additive effect on muscle mass. This concept may be even more relevant to explore for novel pharmacological interventions where risk profiles may inhibit long term use.…”