Background Cystic fibrosis (CF) is a multi-system disease that causes chronic respiratory failure, malnutrition and poor growth as a result of a negative energy balance due to maldigestion and malabsorption. Achieving linear growth and height above the 50 th percentile is associated with improved lung function. In October 2022, the use of Elexacaftor/Tezacaftor/Ivacaftor (ETI) was approved for children with CF from the age of 6 years. Analyses on the effect of ETI on height velocity (HV) are not usually available from trial and real life data and our work aims to study growth pattern by HV. A secondary aim was to check for any differences according to the CFTR variants severity. Methods We conducted a single-center prospective study at the CF Unit of the Bambino Gesù Children’s Hospital, including children aged 6-11 years who were eligible for ETI. The whole population of 24 people with CF (pwCF) underwent evaluation of height, weight, body mass index (BMI), bone mineral density (BMD), body composition analysis with bioelectrical impedance analysis (BIA), and muscle weakness using the one-minute sit-to-stand test (1STST) before starting the new drug. Height, weight, height velocity (HV), BMI standard deviation scores (SDS) were calculated for both 6 months before and 6 months after the start of ETI treatment. Results The mean age of the population was 8.7 years (SD 1.87), with a balanced gender distribution (F/M 12/12) and majority naïve to previous CFTR modulators. We found a significant difference in the growth rate achieved when comparing the calculated mean HV between T (-6 months) and T0 (4.2±2.0 cm/year; -1.96±2.4 SDS) with the HV between T0 and T (+6 months) (7.1±3.0 cm/year; +1.5±3.7 SDS) (p<0.0001). The group with F508del/minimal function mutations (F/MF) – 15 pwCF – had a higher average speed than those with homozygous F508del (F/F) – 5 pts – and those with F508del/residual function mutations (F/RF) – 4 pts – ( p< 0.0001). We found no significant differences in the three different genetic groups concerning BMD and initial lean mass. Conclusion The results highlight the benefit of ETI in the pediatric CF population, particularly by increasing the HV in children aged 6-11, especially those with the F/MF genotype. This study further emphasizes the impact of CFTR restoration on a fundamental aspect of the CF child’s well-being, growth.

Background: Multiple Breath washout (MBW) represents an important tool to detect early a possible pulmonary exacerbation especially in Cystic Fibrosis (CF) disease. Lung clearance index (LCI) is the most commonly reported multiple breath washout (MBW) index and in the last years was used as management measure for evaluation. Our aim was to analyze clinical utility of LCI index variability in pulmonary exacerbation in CF. Methods: A single-center study was conducted at CF Unit of Bambino Gesù Children’s Hospital among hospitalized > 3 years patients for pulmonary exacerbations and treated with antibiotic intravenous treatment for 14 days. MBW and spirometry were evaluated within 72 hours of admission to hospital and at the end of hospitalization. Descriptive analysis was conducted and correlations between quantitative variables were investigated. Results: Fifty-seven patients (M22/F35) with an average age 18.56 (± 8.54) years were enrolled. LCI 2.5 was significantly reduced at the end of antibiotic treatment in both pediatric and adult populations with an average improvement of -6% in 37/57 patients. 26/57 are stable in LCI values. A significant elevation of +7.30% was found for FEV1%. 4/57 (7.02 %) had a significant deterioration in LCI values at the end of IV antibiotic treatment. A positive good correlation among LCI 2.5 and Scond (rho= +0.615, p=0.000) and LCI 2.5 and Sacin (rho=+0.649, p=0.000) and a negative strong correlation between FEV1% and LCI 2.5 were found in post treatment period. A better increase of LCI 2.5 in < 18 years (-10.27% vs -4.57%) than adult was noticed. Conclusions: LCI may have a role in the routine clinical care of CF patients as a good tool to assess response to intravenous antibiotic therapy.