Changes of inflammatory markers in nasal lavage samples after 2 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 cohort and an 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), interleukin (IL)-1β, IL-6, IL-8 and vascular endothelial growth factor (VEGF). Cytokines were compared to a sex- and age-matched healthy control group. Results: In total, 44 paediatric and adult patients and 49 healthy controls were enrolled in this study. In the paediatric cohort, NE levels decreased (p≤0.05) and reached values comparable to those of healthy controls, whereas the remaining cytokines were within the normal range at baseline. 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-month observation period, while IL-6 showed no significant change. Conclusion: Our data demonstrate changes in inflammatory markers 2 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 healthy controls 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.