title: Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.
abstract: Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established.
  
  
  
  To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections.
  
  
  
  We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans.
  
  
  
  Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging.
  
  
  
  Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.
authors.affiliation: 1 Department of Medicine.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Hisert
authors.affiliation: 2 Department of Pediatrics.
authors.forename: Sonya L
authors.initials: SL
authors.lastname: Heltshe
authors.affiliation: 2 Department of Pediatrics.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pope
authors.affiliation: 3 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California.
authors.forename: Peter
authors.initials: P
authors.lastname: Jorth
authors.affiliation: 4 Department of Genome Sciences.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: 5 Department of Radiology, and.
authors.forename: Rachael M
authors.initials: RM
authors.lastname: Edwards
authors.affiliation: 6 Department of Microbiology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Matthew
authors.initials: M
authors.lastname: Radey
authors.affiliation: 7 Department of Pediatrics, University of Colorado, Aurora, Colorado.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Accurso
authors.affiliation: 2 Department of Pediatrics.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wolter
authors.affiliation: 8 St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Gordon
authors.initials: G
authors.lastname: Cooke
authors.affiliation: 9 Department of Internal Medicine, University of Iowa, Iowa City, Iowa; and.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Adam
authors.affiliation: 8 St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Carter
authors.affiliation: 8 St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Brenda
authors.initials: B
authors.lastname: Grogan
authors.affiliation: 9 Department of Internal Medicine, University of Iowa, Iowa City, Iowa; and.
authors.forename: Janice L
authors.initials: JL
authors.lastname: Launspach
authors.affiliation: 10 Trinity College Dublin, Dublin, Ireland.
authors.forename: Seamas C
authors.initials: SC
authors.lastname: Donnelly
authors.affiliation: 8 St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Gallagher
authors.affiliation: 4 Department of Genome Sciences.
authors.forename: James E
authors.initials: JE
authors.lastname: Bruce
authors.affiliation: 9 Department of Internal Medicine, University of Iowa, Iowa City, Iowa; and.
authors.forename: David A
authors.initials: DA
authors.lastname: Stoltz
authors.affiliation: 9 Department of Internal Medicine, University of Iowa, Iowa City, Iowa; and.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welsh
authors.affiliation: 2 Department of Pediatrics.|6 Department of Microbiology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Lucas R
authors.initials: LR
authors.lastname: Hoffman
authors.affiliation: 8 St. Vincent's University Hospital, Dublin, Ireland.
authors.forename: Edward F
authors.initials: EF
authors.lastname: McKone
authors.affiliation: 1 Department of Medicine.|6 Department of Microbiology, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
mesh_terms: D000328:Adult; D000627:Aminophenols / Q000627:therapeutic use*; D065101:Chloride Channel Agonists / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D015363:Quinolones / Q000627:therapeutic use*; D012141:Respiratory Tract Infections / Q000378:metabolism / Q000517:prevention & control*; D013183:Sputum / Q000187:drug effects / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D000627:Aminophenols; D065101:Chloride Channel Agonists; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor
keywords: Pseudomonas aeruginosa; cystic fibrosis; inflammation; ivacaftor