Height Velocity in Pediatric Cystic Fibrosis Under Triple CFTR Modulator Therapy: A Real-Life Monocentric Experience.

Cystic fibrosis (CF) is a multi-system disorder characterized by chronic respiratory failure, malnutrition, and impaired growth. Achieving linear growth above the 50th percentile is associated with better pulmonary outcomes. Since October 2022, Elexacaftor/Tezacaftor/Ivacaftor (ETI) has been approved in Italy for children aged ≥6 years. However, data on its impact on height velocity (HV) remain lacking. This study aims to evaluate growth patterns by HV and explore differences according to the CFTR variant genotype. We conducted a prospective single-center study at the CF Unit of Bambino Gesù Children's Hospital involving 24 children aged 6-11 years eligible for ETI treatment. Baseline assessments included height, weight, body mass index (BMI), bone mineral density (BMD), body composition (via bioelectrical impedance analysis, BIA), and muscle strength (one-minute sit-to-stand test (1STST)). Height, weight, HV, and BMI standard deviation scores (SDS) were calculated for the 6 months before and after ETI initiation. The mean age of the cohort was 8.7 ± 1.9 years (F/M: 12/12), with most patients naïve to CFTR modulators. A significant increase in HV was observed post-ETI: from 4.2 ± 2.0 cm/year (-1.96 ± 2.4 SDS) in the 6 months before treatment to 7.1 ± 3.0 cm/year (+1.5 ± 3.7 SDS) after treatment initiation ( < 0.0001). Patients with F508del/minimal function (F/MF) genotypes (n = 11) showed significantly greater HV compared to those with F508del/F508del (F/F, n = 5) and F508del/residual function (F/RF, n = 8) genotypes ( < 0.0001). No significant differences were observed among genetic groups in baseline BMD or lean mass. ETI treatment significantly and rapidly improves HV in children with CF, particularly in those with F/MF genotypes. These findings underscore the role of CFTR modulator therapy in promoting linear growth, a key indicator of health in pediatric CF populations.