title: Medical reversal of chronic sinusitis in a cystic fibrosis patient with ivacaftor.
abstract: BACKGROUND
  Chronic sinusitis is universal in cystic fibrosis (CF) and our current treatments are ineffective in reversing sinus disease. The objective of this work was to determine if increasing CF transmembrane conductance regulator (CFTR) activity by ivacaftor could treat CF sinus disease and assess its effect on primary sinus epithelial cultures.
  
  
  METHODS
  Case report of 1 patient with long-standing chronic sinus disease and a new diagnosis of CF with a mild mutation (P205S) and a severe mutation (G551D). We discuss clinical changes in symptoms, radiographic findings, nasal potential difference testing, and nasal pH values before and after treatment with ivacaftor. We then developed primary sinonasal epithelial cell cultures from a biopsy of the patient to determine changes in airway surface liquid (ASL) pH and ASL viscosity after ivacaftor treatment.
  
  
  RESULTS
  Ivacaftor treatment reversed CT findings of CF sinus disease, increased nasal voltage and pH, and resolved sinus symptoms after 10 months of therapy. Ivacaftor significantly increased ASL pH and decreased ASL viscosity in primary airway cultures.
  
  
  CONCLUSIONS
  This report documents the reversal of CF sinus disease. Based on our in vivo and in vitro results, we speculate that ivacaftor may reverse CF sinusitis by increasing ASL pH and decreasing ASL viscosity. These studies suggest that CFTR modulation may be effective in treating CF and perhaps non-CF sinusitis.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA.
authors.forename: Eugene H
authors.initials: EH
authors.lastname: Chang
authors.forename: Xiao Xiao
authors.initials: XX
authors.lastname: Tang
authors.forename: Viral S
authors.initials: VS
authors.lastname: Shah
authors.forename: Janice L
authors.initials: JL
authors.lastname: Launspach
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ernst
authors.forename: Brieanna
authors.initials: B
authors.lastname: Hilkin
authors.forename: Philip H
authors.initials: PH
authors.lastname: Karp
authors.forename: Mahmoud H
authors.initials: MH
authors.lastname: Abou Alaiwa
authors.forename: Scott M
authors.initials: SM
authors.lastname: Graham
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Hornick
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.forename: Joseph
authors.initials: J
authors.lastname: Zabner
mesh_terms: D000627:Aminophenols / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D002648:Child; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D015363:Quinolones / Q000627:therapeutic use*; D020545:Respiratory Mucosa / Q000502:physiology; D012852:Sinusitis / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D014783:Viscosity
chemical_list: D000627:Aminophenols; D000893:Anti-Inflammatory Agents; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: ASL; CF; CFTR; airway surface liquid; cystic fibrosis; ivacaftor