Plethysmography as a Complementary Tool for Monitoring Response to CFTR Modulator Therapy in Children with Cystic Fibrosis: A Real-World Study

Background: Sensitive tools for monitoring response to cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy remain needed in children with cystic fibrosis (CF). Plethysmography may provide complementary information to spirometry and multiple-breath nitrogen washout (MBNW). Aim: To characterize longitudinal changes in plethysmographic parameters before and during CFTR modulator therapy in children and adolescents with CF, using spirometry and MBNW as complementary physiological assessments. Methods: This retrospective observational study included 67 children with CF. Forty-nine patients received elexacaftor/tezacaftor/ivacaftor (ETI) and 18 received tezacaftor/ivacaftor (TI). Spirometry, plethysmography, and MBNW were performed at baseline and at follow-up, typically 12 months after treatment initiation, but no later than 24 months. Health-related quality of life was assessed using the Cystic Fibrosis Questionnaire–Revised (CFQ-R) in 42 ETI-treated patients with complete paired data. Pulmonary exacerbations requiring intravenous antibiotic treatment were also analyzed. Results: During ETI treatment, significant within-group changes were observed in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), lung clearance index (LCI2.5), airway resistance, total lung capacity (TLC), and the residual volume-to-total lung capacity ratio (RV/TLC). Improvements in selected CFQ-R domains and a reduction in pulmonary exacerbations requiring intravenous antibiotics were also observed in the ETI group, although the between-group difference in exacerbation changes was not statistically significant. Conclusions: Plethysmography, particularly airway resistance and RV/TLC, may provide complementary information to spirometry and MBNW when monitoring pulmonary function changes during CFTR modulator therapy in pediatric CF.