Low muscle mass in interstitial lung disease: a systematic review and meta-analysis of prevalence and clinical associations

BACKGROUND: Low muscle mass, a component of sarcopenia, is increasingly recognised as a marker of poor physiological reserve in chronic diseases. While observed in patients with interstitial lung disease (ILD), its prevalence and clinical associations remain inadequately characterised. Furthermore, heterogeneous diagnostic approaches from CT-derived indices to consensus definitions complicate evidence interpretation. METHODS: We conducted a systematic review and meta-analysis to estimate the prevalence of low muscle mass and/or consensus-defined sarcopenia in ILD. Six databases were searched (1988–March 2024). Eight studies comprising 829 patients (701 with idiopathic pulmonary fibrosis [IPF]) met inclusion criteria. The included CT-based studies defined low muscle mass using cohort-specific lowest-quartile cut-offs, which do not meet consensus diagnostic criteria for sarcopenia. RESULTS: The pooled prevalence of low muscle mass and/or sarcopenia was 24.3% (95% CI: 19.7–29.0) with substantial heterogeneity (I²=59.2%). A sensitivity analysis restricted to consensus-defined sarcopenia yielded a 27.5% prevalence with moderate heterogeneity (I²=62.5%); however, studies within their respective consensus frameworks (EWGSOP2 or AWGS) demonstrated zero internal heterogeneity (I²=0%). In contrast, CT-based studies using cohort-specific thresholds showed marked variability (I²=75.8%). Meta-regression confirmed diagnostic method (p = 0.044) and mean BMI (p = 0.003) as significant moderators. Low muscle mass was significantly associated with reduced pulmonary function, including lower FVC% predicted (effect size − 0.477, p < 0.001) and DLCO% predicted (effect size − 0.389, p = 0.003), as well as advancing age and lower BMI. CONCLUSIONS: While low muscle mass or consensus-defined sarcopenia affects approximately one in four ILD patients, this prevalence is largely representative of the IPF phenotype. Muscle mass abnormalities are significantly associated with respiratory decline, supporting muscle depletion as a clinically relevant marker with potential prognostic implication. However, substantial heterogeneity, driven by CT-based cohort-specific quartiles rather than externally validated thresholds, restricts the precision of current prevalence estimates. Future research should employ standardised consensus definitions, differentiate isolated muscle depletion from systemic wasting syndromes, use externally validated cut-offs, adopt multicentre prospective designs.