Airway nitric oxide production in patients with cystic fibrosis increases with ivacaftor therapy

Abstract

Introduction: Nitric oxide (NO) plays an important role in the regulation of airway caliber & host defense against certain bacteria. NO is reduced in cystic fibrosis (CF) airways & NO deficiency may contribute to CF lung disease. The mechanisms resulting in reduced airway NO formation in CF are incompletely understood but previous studies suggest a direct link between CFTR dysfunction & low NO production from NO synthases. Method: We studied the effect of ivacaftor, a new treatment targeting CFTR, on airway NO in people with CF. A total of 15 (7 pediatric and 8 adult) patients with CF were recruited. All carried one copy of a CFTR-gating mutation, and 11 were F508del compound heterozygote. Mean age at enrolment was 23 (range 6-58) years. Pulmonary function (spirometry) and fraction of exhaled NO (FENO50) were measured before and 4 weeks after initiation of ivacaftor treatment. Results: Both mean (±SD) forced vital capacity (90.7±12.2 vs 100.4±8.7 % of predicted, p Conclusion: Ivacaftor treatment results in a significant increase in exhaled airway NO. These data suggest that CFTR-targeting therapies may result in reconstitution of impaired airway NO formation in patients with CF, and show that an increase in airway NO formation is associated with improved pulmonary function in patients with CF.