ETI therapy greatly improves lung clearance index in children with cystic fibrosis: Study
A new study published in the Journal of Cystic Fibrosis showed that elexacaftor/tezacaftor/ivacaftor (ETI) therapy significantly reduced the Lung Clearance Index (LCI) in children with cystic fibrosis (CF), which indicated improved ventilation distribution. Also, the greatest improvements were seen in those with more severe disease.
By focusing on the underlying CFTR malfunction rather than its aftereffects, ETI has revolutionized the treatment of cystic fibrosis. Beyond advancements in spirometric measurements, ventilation inhomogeneity has drawn more attention. Multiple breath washout yields the LCI, which offers a reliable evaluation of the distribution of ventilation worldwide. Recent research demonstrates that ETI considerably lowers intra- and inter-individual LCI variability and increases breathing homogeneity.
These alterations point to increased small airway patency, more stable airway function, and improved physiological measurement reliability under very successful CFTR regulation. The objectives of this study were to assess within-patient LCI variability prior to and following therapy, quantify changes in LCI following ETI commencement using repeated measurements, and investigate associations between LCI alterations and clinical indicators.
A typical juvenile CF cohort's longitudinal clinical data was retrospectively analyzed for this study. LCI variability assessment and comparison of mean LCI before and under treatment were made possible by many measurements per patient within 12 months prior to and following ETI commencement. Researchers evaluated changes in within-patient LCI variability, sweat chloride, genotype, FEV₁ z-score, baseline LCI, and the LCI response to ETI.
With a significant decrease in within-patient LCI variability from 7.9% (4.3–10.2%) to 4.9% (3.4–6.7%), the mean LCI in 59 patients (median age 11.6 years) dropped from 7.9 (IQR 6.9–9.4) to 6.4 (6.1–7.0) (p < 0.001). LCI improvement had a modest correlation (r = -0.36) with baseline FEV₁ and a strong correlation (r = 0.73) with baseline LCI. Sweat chloride, baseline FEV₂, homozygous F508del genotype, and baseline LCI were all significant predictors of LCI change in multivariable analysis.
The patients with baseline LCI >10 had more varied LCI responses. Overall, in children with cystic fibrosis (CF), ETI improves ventilation inhomogeneity; the degree of LCI reduction is highly correlated with the severity of the disease at baseline. Greater illness stability is indicated by a decrease in within-patient LCI variability.
Source:
Arn-Roth, T., Bernasconi, T., Frauchiger, B. S., Korten, I., Casaulta, C., Kieninger, E., & Latzin, P. (2025). Improved ventilation inhomogeneity and lower LCI variability under ETI: Retrospective analysis in a pediatric cohort. Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society. https://doi.org/10.1016/j.jcf.2025.12.016
