title: Effect of ivacaftor therapy on exhaled nitric oxide in patients with cystic fibrosis.
abstract: Airways of patients with cystic fibrosis are deficient for nitric oxide. Low nitric oxide in cystic fibrosis has been shown to be associated with poor pulmonary function and risk of infection with certain pathogens. Treatment of cystic fibrosis patients with the cystic fibrosis transmembrane conductance regulator (CFTR)-targeting drug ivacaftor results in improved pulmonary function. The effect of ivacaftor on airway nitric oxide has not been assessed.
  
  
  METHODS
  In this observational trial, fractional exhaled nitric oxide (FE(NO)) was measured before and 4 weeks after initiation of ivacaftor therapy, in patients with cystic fibrosis and a CFTR gating mutation. The effect of ivacaftor on FE(NO) was compared to treatment with inhaled dornase alfa or hypertonic saline for 4 weeks, respectively.
  
  
  RESULTS
  A total of 15 patients on ivacaftor therapy were studied. Pulmonary function improved significantly and mean (±SD) FE(NO) increased from 8.5±5.0 to 16.2±15.5 ppb. The effect was more pronounced in pediatric compared to adult patients. There was no linear correlation between changes in FE(NO), pulmonary function or sweat chloride concentration. Neither treatment with inhaled dornase alfa (n=15) or hypertonic saline (n=16) resulted in a change in FE(NO).
  
  
  CONCLUSIONS
  Therapy with ivacaftor results in an increase in nitric oxide formation in cystic fibrosis airways, while dornase alfa or hypertonic saline has no effect on airway nitric oxide. Some beneficial effects of CFTR targeting therapy in CF may result from improved airway nitric oxide production.
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada; Program in Physiology and Experimental Medicine, SickKids Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Grasemann
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada; Program in Physiology and Experimental Medicine, SickKids Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Tanja
authors.initials: T
authors.lastname: Gonska
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Avolio
authors.affiliation: Program in Physiology and Experimental Medicine, SickKids Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Klingel
authors.affiliation: Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Canada.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tullis
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada; Program in Physiology and Experimental Medicine, SickKids Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
mesh_terms: D000328:Adult; D000627:Aminophenols / Q000627:therapeutic use*; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D045853:Exhalation; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D015363:Quinolones / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000627:Aminophenols; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; D009569:Nitric Oxide
keywords: Cystic fibrosis; Ivacaftor; Nitric oxide; Pulmonary function