Once-daily hypertonic saline inhalation and airway clearance techniques in children with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor: a prospective multicentre study.

Background

Highly effective CFTR modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) have improved outcomes in cystic fibrosis (CF), with many children now experiencing minimal respiratory symptoms. This raises questions about the need for continued hypertonic saline inhalation and airway clearance techniques (ACTs).

Methods

In this prospective multicentre observational study, children with CF aged 6-17 years treated with ETI for ≥9 months reduced the prescribed frequency of hypertonic saline inhalation and ACTs from twice daily to once daily over 12 months. The primary outcome was change in lung clearance index (LCI). Secondary outcomes included spirometry, airway microbiology, antibiotic use, and respiratory symptoms. Analyses of longitudinal outcomes were performed using mixed-effects models

Results

Forty-six children were included from two Swedish CF centres. Mean (SD) LCI and FEV1% predicted at baseline were 6.6 (1.1) and 97.2 (6.1), respectively. During the 12 months following treatment reduction, LCI showed a small, non-significant improvement of -0.32 units (95% CI -0.67 to 0.03; P = 0.075), while FEV1% predicted remained stable (mean change 0.02%-points, 95% CI -2.74 to 2.77; P = 0.99). Respiratory symptoms were stable (mean change -2.9 points, 95% CI -9.8 to 4.1; P = 0.41). Antibiotic use decreased from 47 to 29 days per person-year, corresponding to a 39% reduction (95% CI 25%-50%; P < 0.001), with no clinically relevant changes in airway microbiology.

Conclusions

Reduction to once-daily hypertonic saline inhalation and ACTs in children with CF treated with ETI was not associated with clinical deterioration over 12 months and was accompanied by reduced antibiotic use.