Correlation between pulmonary outcomes and nutritional status following treatment with elexacaftor/tezacaftor/ivacaftor in people with Cystic fibrosis

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) improves lung function and nutritional status in people with cystic fibrosis (pwCF); it is unclear whether these responses are correlated, and whether pancreatic status modifies these associations. Methods: Retrospective study including pwCF aged ≥2 years from five Israeli CF centers, treated with ETI for ≥1 year. Demographic, clinical and anthropometric measures were collected at baseline, 1 month and 1 year after ETI initiation, including: forced expiratory volume in 1 s (FEV1), body mass index (BMI), lung clearance index (LCI), sweat chloride (SwCl), sputum cultures, rate of pulmonary exacerbations (PEx) and days of intravenous (IV) antibiotics (Abx). Correlations between pulmonary and nutritional parameters were assessed overall and stratified by pancreatic status. Results: 184 pwCF (age 24.7 ± 14.4 years), 53.3% pancreatic sufficient (PS), 38.6% had chronic Pseudomonas aeruginosa. FEV1% and BMI%ile increased significantly at 1 month, with further improvement at 1 year. Disease burden improved, with significant reductions in LCI, days of IV Abx, PEx, and SwCl. Changes in FEV1% and BMI%ile were modestly correlated at 1 month (r = 0.286, p < 0.001) and 1 year (r = 0.24, p = 0.003). FEV1% improvement correlated with LCI reductions (1 month: r = −0.509, p < 0.001; 1 year: r = −0.443, p < 0.001). Subgroup analyses showed a stronger FEV1%-LCI association in the pancreatic insufficient (PI) subgroup, whereas BMI-related correlations (1 month with IV Abx, 1 year with FEV1) were observed only in PS patients. Conclusions: In a large real-world cohort, ETI led to significant pulmonary and nutritional improvements; pancreatic sufficiency status influenced the pattern and strength of associations, supporting phenotype-aware monitoring after ETI initiation.