title: Concentration of fractional excretion of nitric oxide (FENO): A potential airway biomarker of restored CFTR function.
abstract: BACKGROUND
  Lower airway biomarkers of restored cystic fibrosis transmembrane conductance regulator (CFTR) function are limited. We hypothesized that fractional excretion of nitric oxide (FENO), typically low in CF patients, would demonstrate reproducibility during CFTR-independent therapies, and increase during CFTR-specific intervention (ivacaftor) in patients with CFTR gating mutations.
  
  
  METHODS
  Repeated FENO and spirometry measurements in children with CF (Cohort 1; n=29) were performed during hospital admission for acute pulmonary exacerbations and routine outpatient care. FENO measurements before and after one month of ivacaftor treatment (150 mg every 12h) were completed in CF patients with CFTR gating mutations (Cohort 2; n=5).
  
  
  RESULTS
  Cohort 1: Mean forced expiratory volume in 1s (FEV1 % predicted) at enrollment was 72.3% (range 25%-102%). Mean FENO measurements varied minimally over the two inpatient and two outpatient measurements (9.8-10.9 ppb). There were no clear changes related to treatment of pulmonary exacerbations, gender, genotype or microbiology, and weak correlation with inhaled corticosteroid use (P<0.05). Between the two inpatient measurements, FEV1 % predicted increased by 7.3% (P<0.03) and FENO did not change. In Cohort 2, mean FENO increased from 6.6 ppb (SD=2.19) to 11.8 ppb (SD=4.97) during ivacaftor treatment. Mean sweat chloride dropped by 58 mM and mean FEV1 % predicted increased by 10.2%.
  
  
  CONCLUSIONS
  Repeated FENO measurements were stable in CF patients, whereas FENO increased in all patients with CFTR gating mutations treated with ivacaftor. Acute changes in FENO may serve as a biomarker of restored CFTR function in the CF lower airway during CFTR modulator treatment.
authors.affiliation: Department of Pediatrics, Nationwide Children's Hospital, Columbus, OH, United States.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Kotha
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Szczesniak
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
authors.forename: Anjaparavanda P
authors.initials: AP
authors.lastname: Naren
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Fenchel
authors.affiliation: Department of Mathematical Sciences, University of Cincinnati, Cincinnati, OH, United States.
authors.forename: Leo L
authors.initials: LL
authors.lastname: Duan
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.
authors.forename: Gary L
authors.initials: GL
authors.lastname: McPhail
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States. Electronic address: john.clancy@cchmc.org.
authors.forename: John P
authors.initials: JP
authors.lastname: Clancy
mesh_terms: D000293:Adolescent; D000627:Aminophenols / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism*; D015363:Quinolones / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000627:Aminophenols; D015415:Biomarkers; D015363:Quinolones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C545203:ivacaftor; D009569:Nitric Oxide
keywords: CFTR biomarker; CFTR modulator; Cystic fibrosis; FENO; Nitric oxide