Glucocorticoid-induced muscle weakness in ECOPD: a perspective on mechanisms and emerging pharmacological interventions.

INTRODUCTION: Muscle weakness represents a significant clinical problem in chronic obstructive pulmonary disease (COPD). During exacerbations of COPD (ECOPD), inflammation, oxidative stress, malnutrition, disuse, hypoxia, and glucocorticoid (GC) levels increase and converge, further aggravating skeletal muscle impairment with GC signaling as a common denominator. No intervention currently exists that specifically prevents or counteracts GC-induced muscle weakness during ECOPD.

AREAS COVERED: This review summarizes clinical and pre-clinical evidence on the role of GC signaling in muscle dysfunction during ECOPD. We discuss the underlying molecular mechanisms by which GCs drive muscle weakness, and critically evaluate emerging pharmacological strategies aimed at mitigating these effects. PubMed and Scopus were searched for peer-reviewed papers published before April 2025.

EXPERT OPINION: GC-induced muscle weakness is an under-recognized but potentially modifiable contributor to muscle weakness in ECOPD. Particular promise lies in pharmacological interventions such as myostatin pathway inhibitors, selective androgen receptor modulators, and those inducing IGF-1-related protein synthesis. Dedicated translational and clinical research is urgently needed to evaluate these novel interventions in the setting of ECOPD. Effective countermeasures could preserve muscle mass and function, improve exercise capacity and recovery, shorten hospital stay, and lower the risk of recurrence, offering a new therapeutic opportunity in ECOPD management.