TOPLINE:

In children with cystic fibrosis (CF), elexacaftor/tezacaftor/ivacaftor (ETI) therapy correlated with substantial reductions in Lung Clearance Index (LCI), indicating improved ventilation distribution, with the largest gains in those with more severe disease. 

METHODOLOGY:

• Researchers conducted a retrospective, longitudinal study involving 59 children with CF (median age at ETI initiation, 11.6 years; 66.1% girls) to quantify changes in LCI after ETI initiation, assess within-patient LCI variability pre- and post-ETI, and explore correlations between LCI change and clinical markers.
• Clinical data were collected, including genotype, sweat chloride concentrations, and other routine measurements, during standard follow-up visits every 3 months.
• LCI was measured through nitrogen multiple breath washout test; forced expiratory volume in 1 second (FEV₁) was assessed through spirometry, in accordance with current consensus guidelines.
• The change in LCI was defined as the difference between the mean LCI over the 12 months before and after ETI initiation; the median number of LCI measurements was 4.0 in each period.

TAKEAWAY:

• The median LCI decreased significantly from 7.9 to 6.4 turnovers after ETI initiation, and the proportion of patients within the normal range increased from 33.9% to 78.0% (P < .001 for both).
• Within-patient variability in LCI declined significantly to 4.9% during ETI therapy from 7.8% before treatment, suggesting improved disease stability; the number of reported pulmonary exacerbations or infections per patient also significantly decreased (P < .001 for both).
• Reduction in LCI with treatment strongly correlated with baseline LCI (correlation coefficient [r], 0.73; P < .001) and showed a weak correlation with baseline z-score for FEV₁ (r, -0.36; P < .01).
• Baseline LCI, homozygous F508del genotype, baseline z-score for FEV₁, and baseline sweat chloride concentration were each significant predictors of LCI improvement.

IN PRACTICE:

“The reduction in LCI variability under ETI suggests a more stable disease course, which may, in the long term, allow for less frequent routine monitoring,” the authors wrote.

SOURCE:

The study was led by Tabitha Arn-Roth, Bern University Hospital, University of Bern, Bern, Switzerland. It was published online on December 25, 2025, in the Journal of Cystic Fibrosis.

LIMITATIONS:

The study was retrospective and relied on preexisting records. It was conducted at a single center and included patients within a relatively narrow age range, limiting the generalizability of the findings to broader patient populations or other clinical settings.

DISCLOSURES:

The study was supported by the Swiss National Science Foundation and Vertex Pharmaceuticals. Several authors disclosed receiving grants from or holding contracts with; receiving payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from; and/or participating on data safety monitoring boards or advisory boards of various pharmaceutical companies, including Vertex Pharmaceuticals.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.