INTRODUCTION

Elexacaftor/tezacaftor/ivacaftor (ETI) is a breakthrough therapy for cystic fibrosis (CF). We aimed to assess ETI's real-world impact on peripheral airway disease assessed as ventilation distribution inhomogeneity using nitrogen multiple breath washout (NMBW) in children aged 6-17 years. Additionally, we compared the two outcomes, lung clearance index (LCI), and ventilation distribution efficiency (VDE), as VDE is considered to adjust for a theoretical overestimation of lung disease when using LCI.

METHODS

This nationwide study included data from NMBW performed during routine clinical care. Linear mixed effect regression was used to assess changes in LCI and VDE after 12 months of ETI treatment. Subgroup analyses included baseline age (6-11 vs. 12-1 years) and disease severity (normal-moderate vs. severe-very severe).

RESULTS

We included 131 children (78% homozygous for F508del mutation, mean [SD] age 11.5 [3.4]), and 339 NMBW tests. The median (range) number of tests per child was 3 (1-10). The estimated mean (95% CI) 12-months post-ETI improvement in LCI and VDE were 1.7 units (-2.1; -1.2, p < 0.001) and 2.1%-point (1.6; 2.6, p < 0.001), respectively. Similar LCI and VDE improvements were observed across age groups. Using VDE, fewer children were categorized with very severe lung disease, and the ETI-effect did not differ between the severity groups, unlike LCI.

CONCLUSION

Our research demonstrates that ETI treatment significantly improves lung function, as measured by NMBW, in Danish children and adolescents with CF. VDE improvements were consistent across age and disease severity groups. In contrast, LCI revealed larger effect estimates for those with severe to very-severe lung impairment.