Author(s): GRUET, M., BRONSTEIN, A., ZITTA, E., SAIDI, O., GORIOT-RAYNAUD, N., MELY, L., Institution: UNIVERSITÉ DE TOULON, Country: FRANCE, Abstract-ID: 1257

INTRODUCTION:
Peripheral muscle dysfunction is a well-recognised manifestation of cystic fibrosis [1], impacting exercise tolerance and quality of life, but its persistence in the era of highly effective CFTR modulators remains unclear. In particular, adequately powered controlled studies combining comprehensive assessments of peripheral muscle function and muscle size remain scarce.
METHODS:
Thirty-nine people with cystic fibrosis (age: 31 ± 13 years, BMI: 21 [4.8] kg·m-2; FEV1%: 73 [32] %pred), all receiving CFTR modulator therapy (92% ETI), were compared with 39 healthy controls matched (1:1) for sex and age, using a maximum age difference of two years (mean absolute age difference: 1.1 ± 0.8 years). Muscle function was assessed according to European recommendations [2], through maximal strength and endurance of knee extensors (isometric chair), maximal upper-limb strength (handgrip) and lower-limb explosive performance (squat jump). Quadriceps muscle thickness was measured using ultrasound imaging. Habitual physical activity was assessed over one week using wrist-worn accelerometry.
RESULTS:
Compared with healthy controls, people with cystic fibrosis exhibited significantly reduced quadriceps strength (-23%, p<0.001, d = 0.82), endurance (-29% p<0.001, rrb = 0.46) and thickness (-10%, p=0.006, rrb = 0.36), as well as reduced squat jump performance (-17%, p = 0.01, rrb = 0.34) and handgrip strength (-18%, p=0.009, d = 0.61). Reduction in quadriceps strength persisted when normalised to quadriceps muscle thickness (p=0.007, rrb = 0.35). Habitual physical activity indicators did not differ between groups.
CONCLUSION:
Despite treatment with CFTR modulators, people with cystic fibrosis continue to exhibit substantial peripheral muscle dysfunction. This impairment cannot be explained solely by anthropometric differences, reduced muscle thickness or habitual physical activity levels, suggesting intrinsic alterations in muscle function. These findings support the need for comprehensive assessment of peripheral muscle function in clinical practice and reinforce the relevance of maintaining existing resistance training programmes [3] while developing novel interventions targeting peripheral muscle dysfunction, in the era of highly effective CFTR modulators.

[1] Gruet et al. J Cyst Fibros 2017 16(5):538-552
[2] Saynor et al. Eur Respir Rev 2023; 32: 230029
[3] Gruet et al. J Cyst Fibros 2022 e83–e98