Changes of inflammatory markers in nasal lavage samples after two years of Elexacaftor/Tezacaftor/Ivacaftor therapy in paediatric and adult Cystic Fibrosis patients

Background The introduction of elexacaftor/tezacaftor/ivacaftor (ETI) therapy has markedly improved the prognosis for people with cystic fibrosis (CF). However, its effect on airway inflammation remains a subject of ongoing debate. We aimed to assess the potential long-term impact of ETI on cytokines measured in nasal lavage (NL) samples in a paediatric and adult cohort. Methods This prospective study collected clinical data and NL samples at baseline, weeks 4 and 16, and 1, 1.5, and 2 years after initiation of ETI therapy. The following cytokines were measured: Neutrophil elastase (NE), IL-1β, IL-6, IL-8, and vascular endothelial growth factor (VEGF). Cytokines were compared to a sex- and age-matched, healthy control (HC) group. Results In total, 44 paediatric and adult patients and 49 HC were enrolled in this study. In paediatric patients, NE (p=<0.05) decreased and reached values of HC while other cytokines stayed within values compared to HC. In adults, NE decreased significantly (p=<0.05), but did not reach levels of normal concentrations. IL-8 (p=<0.01) and VEGF (p=<0.05) increased in the 24 months observation period while IL-6 showed no significant change. Conclusion Our data demonstrates changes of inflammatory markers two years after starting ETI therapy; however, these changes reached statistical significance only in part. In the paediatric cohort, cytokine levels—except for NE—were already comparable to those of HC at baseline. In the adult cohort, a trend towards increasing values was observed. Further studies are required to confirm NL as a suitable sample material for assessing airway inflammation and to substantiate the trends described in our study.