The role of ETI therapy in managing sinusitis in cystic fibrosis pediatric population: A study on clinical outcomes

Background: Chronic rhinosinusitis (CRS) is a common extrapulmonary manifestation of cystic fibrosis (CF), significantly affecting pediatric patients’ quality of life. TAS2R38 polymorphisms have been implicated in sinonasal innate immunity and may influence CRS severity and treatment response. Data on the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on sinonasal disease in children remain limited. This study evaluates the effects of ETI on CRS severity and explores the influence of atopy and TAS2R38 polymorphisms. Methods: We performed a single-center retrospective cohort study including CF subjects aged 6–18 years treated with ETI. Clinical, endoscopic, radiological, functional, and laboratory data were collected at baseline and after 12 months. CRS severity was assessed using Lund–Kennedy score, Lund–Mackay CT score, and Visual Analogue Scale (VAS). Secondary outcomes included quality of life (CFQ-R), lung function (FEV1), airway microbiology, atopy, and TAS2R38 genotype. Appropriate parametric and non-parametric tests were used (p < 0.05). Results: Fifty-four patients (mean age 11.5 ± 3.6 years) were included. After 12 months of ETI, significant improvements were observed in FEV1, CFQ-R, VAS, endoscopic and radiological CRS scores. No patient required sinonasal surgery during follow-up. Staphylococcus aureus colonization was significantly reduced. Atopic patients showed lower radiological improvement than non-atopic subjects. TAS2R38 genotype was associated with baseline radiological severity, with higher Lund-Mackay scores in AVI/AVI patients. A genotype-dependent trend in ETI response was observed, with PAV/PAV patients showing less radiological improvement. Conclusions: ETI significantly improves CRS severity in pediatric CF patients. Atopy and genetic modifiers may contribute to variability in sinonasal response, supporting personalized management of CF-related CRS.