S16 The influence of the CFTR modulator ivacaftor on aspergillosis in cystic fibrosis

Introduction Cystic fibrosis (CF) is a life limiting genetic condition which occurs due to mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). Absence of functional CFTR protein leads to progressive respiratory disease characterized by bronchiectasis and chronic infections. CF lung disease predisposes patients to infection and sensitivity to the fungal pathogen Aspergillus fumigatus. Novel CFTR modulating therapies have recently been associated with potential disease modification in CF. It is unclear whether these therapies will have an influence on susceptibility to Aspergillus related disease in CF. Methods We conducted a retrospective cohort study examining patients who commenced the CFTR modulator ivacaftor. Over a period of 5 years we monitored the isolation ofAspergillus in sputum samples and patients’ serological response to Aspergillus fumigatus. Results In 40 patients, ivacaftor therapy resulted in a significant decrease in sweat chloride (from 112 [102.75 – 119.25] to 45 [37 – 61], p Conclusion Effective CFTR modulation in patients with CF does not appear to alter susceptibility or reaction to Aspergillus fumigatus in clinical settings. These findings suggest that Aspergillus will remain a significant pathogen in a new era of CF when most patients will receive CFTR modulator therapy. This will potentially result in clinical challenges due to difficult drug-drug interactions between –azole medications and CFTR modulators.