Background/Objectives: Cystic fibrosis transmembrane conductance regulator modulator (mCFTR) therapy has been proven efficacious in controlled clinical trials for individuals with cystic fibrosis. This post-approval retrospective study aimed to determine the comprehensive effects of elexacaftor/tezacaftor/ivacaftor (ETI) on nutritional status, the respiratory system and quality of life over 12 months of clinical use in paediatric patients treatment-naïve to mCFTR. Methods: A retrospective analysis of records of CF adolescents on ETI therapy was conducted. The selected parameters of anthropometric measurements, body composition assessed by BIA, spirometry, and multiple breath nitrogen washout (MBNW) to measure lung clearance index (LCI), were evaluated before therapy and at 3 and 12 months after treatment initiation. Additionally, children completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results: Over 18 months, data from 58 patients (mean age 14.34 ± 1.70, 50% female; 43% homozygous F508del) on ETI were collected. Body weight increased significantly over 12 months, with a mean gain of 3.33 kg at 3 months (p < 0.001) and 7.10 kg at 12 months (p < 0.001), alongside improvements in BMI z-score, fat-free mass, and fat mass. Significant changes (p < 0.001) were also observed after 3 and 12 months in ppFEV₁ (8.91 ± 8.23; 9.67 ± 8.77) and ppFVC (4.46 ± 5.24; 4.61 ± 5.70), with a decrease in LCI (−1.62 ± 2.15; −1.68 ± 1.89). The CFQ-R Respiratory score increased by 11.75 points and correlated with most of the pulmonary and nutritional parameters. Conclusions: In real-world settings, clinical improvement during ETI therapy reflects a comprehensive impact on nutritional status, body composition, pulmonary function, and quality of life for adolescents with CF.

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 (LCI_2.5), 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.

Cystic fibrosis (CF) is caused by a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene and is characterized by recurrent pulmonary infections, fat malabsorption, and malnutrition. CF is associated with diverse dermatologic symptoms, including aquagenic palmoplantar keratoderma, nutrient deficiency dermatitis, and vasculitis. Sporadically, these manifestations may represent the initial symptoms of cystic fibrosis. Drug-induced skin reactions are commonly observed in patients with cystic fibrosis (pwCF) due to the chronic use of antibiotics. Therapy with CFTR modulators is considered the gold standard in the treatment of cystic fibrosis. Nevertheless, they are associated with numerous side effects, ranging from rash to Stevens-Johnson syndrome. Identifying the cutaneous manifestations of cystic fibrosis may support comprehensive care for patients. In this regard, dermatologists may play an important role in the management of associated skin complications.