A CFTR modulator therapy might improve ciliary beating in patients with cystic fibrosis

<bold>Background:</bold> In cystic fibrosis (CF), mucociliary clearance (MCC) is impaired due to mucus abnormalities, but we also showed an abnormal ciliary beating. The symptomatic CF lung disease management aims to improve MCC, to decrease chronic inflammation, and to treat or prevent respiratory infection. CF patients can also beneficiate from CFTR modulators, aiming to restore the CFTR protein function, and having a highly significate clinical efficacy. An <italic>in vitro</italic> study suggested that CFTR modulators might improve ciliary beat frequency (CBF) in CF patients, but no study evaluated their <italic>ex vivo</italic> effect on ciliary beating. <bold>Aim:</bold> To evaluate if ciliary beating is improved in CF patients treated with CFTR modulators. <bold>Methods:</bold> Ciliary beating was evaluated from ciliated epithelial samples obtained by nasal brushing from 25 CF patients, before starting a CFTR modulators therapy, after 4-8 months, and after 12 months of treatment. CFTR modulator therapies were either lumacaftor/ivacaftor, ivacaftor/tezacaftor or elexacaftor/tezacaftor/ivacaftor. CBF and the percentage of abnormal beat pattern (CBP) were evaluated using ciliary videomicroscopy at 37°C. <bold>Results:</bold> 12/25 CF patients (mean age: 23.7±10.0years) had 3 successful nasal brushings. First, our results confirm that the percentage of abnormal CBP is increased in CF patients, compared with our normal values (p<0.0001; matched for age). Second, in CF patients, there was no significant change over time for CBF (p=0.117), but, the percentage of abnormal CBP decreased over time (p=0.006). <bold>Conclusion:</bold> This study suggested that a CFTR modulator therapy might improve ciliary beating <italic>ex vivo</italic>, and that this could contribute to the MCC improvement in CF patients.