title: Peripheral muscle abnormalities in cystic fibrosis: Etiology, clinical implications and response to therapeutic interventions.
abstract: Peripheral muscle dysfunction is an important systemic consequence of cystic fibrosis (CF) with major clinical implications, such as exercise intolerance and reduced quality of life. Evidence is now accumulating that lack of physical activity is unlikely to be the sole explanation for peripheral muscle dysfunction of patients with CF. Particularly, the demonstration of CFTR expression in both murine and human skeletal muscle suggests the potential implication of intrinsic CF-related factors. By combining data from both human and animal models, this review describes CF peripheral muscle abnormalities and critically reviews the advances in understanding the impact of the underlying mechanisms. We also describe how peripheral muscles respond to intervention in this population. Methodological concerns and directions for future research are also considered. Peripheral muscle atrophy and weakness is prevalent in patients with CF and associated with reduced aerobic and anaerobic performances. Further investigations are however needed to confirm alterations in peripheral muscle endurance and fatigability. Physical inactivity is probably the major contributor of peripheral muscle abnormalities in patients with CF with mild-to-moderate phenotypes. However, the relative influence of additional factors (e.g. inflammation, metabolic abnormalities) probably increases with disease severity making specific and individualized interventions necessary in severe patients. Exercise training is the most effective intervention to address peripheral muscle dysfunction but other strategies, such as neuromuscular electrical stimulation and nutritional or hormonal supplementation may be of interest in some patients. Investigations are needed to determine whether pharmacological interventions such as CFTR modulators are effective to address this condition. To better elucidate the etiology of peripheral muscle dysfunction in CF, future studies should combine measurements at the cellular level with indices of muscle function and monitor physical activity levels to account for its potential effects on muscle function.
authors.affiliation: Université de Toulon, Université Côte d'Azur, LAMHESS, France. Electronic address: gruet@univ-tln.fr.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Gruet
authors.affiliation: KU Leuven, Department of Rehabilitation Sciences, Leuven, Belgium; University Hospitals Leuven, Respiratory Rehabilitation and Respiratory Division, Leuven, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Troosters
authors.affiliation: Grenoble-Alpes University, HP2 Laboratory, 38000 Grenoble, France; INSERM, U1042, 38000 Grenoble, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Verges
mesh_terms: D000203:Activities of Daily Living / Q000523:psychology; D003550:Cystic Fibrosis / Q000150:complications*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D019468:Disease Management; D006801:Humans; D018908:Muscle Weakness / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D011788:Quality of Life
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Aerobic function; CFTR; Cystic fibrosis; Exercise interventions; Muscle function; Muscle metabolism; Nutritional status