Objective: The study evaluated the effects of elexacaftor/tezacaftor/ivacaftor (ETI) therapy in people with cystic fibrosis (pwCF) and a clinical history of Aspergillus fumigatus (AF) infection.

Methods: This prospective cohort study included pwCF who initiated ETI therapy and had received antifungal treatment in the preceding five years due to allergic bronchopulmonary aspergillosis (ABPA group) or other AF-related clinical manifestations (AF group). A control group of pwCF with no prior respiratory cultures positive for AF was also included. Changes from baseline to 12 months in spirometry measures and lung clearance index (LCI2.5), as well as respiratory colonization by AF, were compared across groups. Annual fold changes in the geometric mean of immunological markers were estimated using generalized estimating equations with a piecewise linear spline model, fitted to data collected from three years before to one-year post-ETI.

Results: The study included 16 patients in the ABPA group, 47 in the AF group, and 45 controls. Spirometry and LCI2.5 improvements were comparable across groups. Positive respiratory cultures decreased from 43.8 to 18.8% in the ABPA group (p = 0.30), and from 78.7 to 23.4% in the AF group (p < 0.001). Total IgE and IgG anti-AF decreased in both the ABPA and the AF groups, with annual reductions of 20-42%. No ABPA episodes occurred during ETI therapy.

Conclusions: During ETI therapy, pulmonary outcomes improved, AF colonization and sensitization decreased, and no episodes of ABPA were observed in pwCF with a clinical history of AF infection.