Background: In people with cystic fibrosis (pwCF), nutritional status is an important prognostic indicator. CF transmembrane conductance regulator (CFTR) modulators can improve both pulmonary function and body weight, but more data is required to assess its effects on body composition.

Aims: To investigate the body composition in pwCF receiving CFTR modulators.

Methods: A deep learning-based, fully automated body composition analysis (BCA) of chest CT scans was performed in pwCF who were or were not receiving mono/ dual-combination CFTR modulator therapy (baseline analysis). In addition, BCA was conducted in people with CF before and after receiving triple-combination elexacaftor/ tezacaftor/ ivacaftor (longitudinal analysis).

Results: At baseline, chest CT-based BCA was performed in 85 pwCF, with 34 (40%) receiving mono/ dual-combination CFTR modulator therapies. Higher adipose tissue ratios were found in those receiving mono/ dual-combination CFTR modulator therapies. Muscle ratio correlated with FEV1 (r=0.569, p<0.001) and six-minute walk test (r=0.392, p<0.001). Fecal elastase was associated with total adipose tissue ratio (r=0.466, p=0.001). Follow-up chest CT scans were conducted in 18 pwCF after starting triple-combination CFTR modulator therapy. Triple-combination therapy was associated with an increase of total adipose tissue ratio (+27%, p=0.007), but muscle ratio remained stable (p=0.304). 

Conclusions: Our findings indicate that CFTR modulator therapies mainly affect adipose tissue rather than muscle tissue in pwCF. In the light of CFTR modulator therapies, nutrition management needs to be adjusted.