Skeletal muscle contributions to reduced fitness in cystic fibrosis youth

Owen William Tomlinson; Alan Robert Barker; Jonathan Fulford; Paul Wilson; James Shelley; Patrick John Oades; Craig Anthony Williams

doi:10.3389/fped.2023.1211547

Skeletal muscle contributions to reduced fitness in cystic fibrosis youth

Front Pediatr. 2023 Jun 14:11:1211547. doi: 10.3389/fped.2023.1211547. eCollection 2023.

Authors

Owen William Tomlinson^{1

2

3}, Alan Robert Barker¹, Jonathan Fulford³, Paul Wilson¹, James Shelley², Patrick John Oades², Craig Anthony Williams^{1

2}

Affiliations

¹ Children's Health and Exercise Research Centre, Public Health and Sports Sciences, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
² Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom.
³ Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.

Abstract

Background: Increased maximal oxygen uptake (V̇O_2max) is beneficial in children with cystic fibrosis (CF) but remains lower compared to healthy peers. Intrinsic metabolic deficiencies within skeletal muscle (muscle "quality") and skeletal muscle size (muscle "quantity") are both proposed as potential causes for the lower V̇O_2max, although exact mechanisms remain unknown. This study utilises gold-standard methodologies to control for the residual effects of muscle size from V̇O_2max to address this "quality" vs. "quantity" debate.

Methods: Fourteen children (7 CF vs. 7 age- and sex-matched controls) were recruited. Parameters of muscle size - muscle cross-sectional area (mCSA) and thigh muscle volume (TMV) were derived from magnetic resonance imaging, and V̇O_2max obtained via cardiopulmonary exercise testing. Allometric scaling removed residual effects of muscle size, and independent samples t-tests and effect sizes (ES) identified differences between groups in V̇O_2max, once mCSA and TMV were controlled for.

Results: V̇O_2max was shown to be lower in the CF group, relative to controls, with large ES being identified when allometrically scaled to mCSA (ES = 1.76) and TMV (ES = 0.92). Reduced peak work rate was also identified in the CF group when allometrically controlled for mCSA (ES = 1.18) and TMV (ES = 0.45).

Conclusions: A lower V̇O_2max was still observed in children with CF after allometrically scaling for muscle size, suggesting reduced muscle "quality" in CF (as muscle "quantity" is fully controlled for). This observation likely reflects intrinsic metabolic defects within CF skeletal muscle.

Keywords: adolescence; exercise capacity; modelling; musculoskeletal; respiratory disease.

Grants and funding

The facility requirements for this study were financially supported by the Discipline of Sport & Health Science at the University of Exeter and the Royal Devon & Exeter CF Research Charitable Fund. In addition, Jonathan Fulford's salary was supported via an NIHR grant to the University of Exeter (CRF/2016/10027). No further funding is reported.