Relationship between skeletal muscle indicators and clinical outcomes in cystic fibrosis is modified by adiposity and CFTR modulator use: a cross-sectional analysis.

BACKGROUND

Muscle mass predicts clinical outcomes in people with cystic fibrosis (PwCF), but muscle quality remains insufficiently characterized. Furthermore, although CFTR modulators promote weight gain, their impact on the relationship between muscle and clinical outcomes is unknown.

OBJECTIVES

To quantify the relationships between skeletal muscle indicators and clinical outcomes in adults with cystic fibrosis (CF) and determine whether CFTR modulators and/or adiposity influence the relationships.

METHODS

This cross-sectional study included 75 adults with CF and 73 controls without CF. Body composition [appendicular skeletal muscle mass index (ASMI), visceral fat, and total body fat] was measured by dual-energy X-ray absorptiometry. Muscle quality (via phase angle) was assessed using bioelectrical impedance analysis. Clinical outcomes included physical functionality [hand grip (HG) strength and 1-min sit-to-stand test result], lung function, and an oral glucose tolerance test result. Sarcopenia was defined as having low muscle mass and low HG strength. Statistical analyses included testing for effect modification in the relationships between variables.

RESULTS

Five PwCF had sarcopenia compared with none of the controls. Despite similar BMI, PwCF had lower ASMI [β: -0.46; 95% confidence interval (CI): -0.88, -0.05; P = 0.02], HG strength (β: -3.6; 95% CI: -6.6, -0.61; P = 0.02), and muscle quality (β: -0.57; 95% CI: -0.93, -0.21; P = 0.01) compared with controls. In PwCF, lung function was positively associated with ASMI among people not taking CFTR modulators but not among users (interaction; β: -9.21; 95% CI: -16.87, -1.55; P = 0.01). Muscle quality (r = 0.35; 95% CI: 0.04, 0.59; P = 0.02) and HG strength (r = 0.36; 95% CI: 0.05, 0.60; P = 0.02) were positively related to insulin sensitivity. The positive relationship between ASMI and physical functionality was only significant among PwCF with low adiposity (interaction; β: -1.9; 95% CI: -3.51, -0.35; P = 0.02).

CONCLUSIONS

Muscle mass, strength, and quality are lower in PwCF than in controls, with muscle strength and quality linked to glucose tolerance. Lung function relationships with muscle mass differ by CFTR modulator use, and excess adiposity attenuates strength-related functional benefits. This study highlights the need for personalized approaches to CF management.