title: Use of ibuprofen to assess inflammatory biomarkers in induced sputum: Implications for clinical trials in cystic fibrosis.
abstract: BACKGROUND
  High-dose ibuprofen (HDI) is a clinically beneficial anti-inflammatory regimen that may be a useful reagent to study induced sputum inflammatory marker changes over short study periods appropriate for early-phase CF clinical trials.
  
  
  METHODS
  We conducted a 28-day, open-label, randomized, controlled trial among 72 clinically stable CF subjects (FEV1≥40% predicted) randomized to HDI or routine care that assessed IL-6, IL-8, TNF-α, IL-1-β, free neutrophil elastase, and white cell counts with differentials change from baseline in induced sputum.
  
  
  RESULTS
  IL-6 was the only biomarker with significant within-group change: 0.13 log10 pg/mL mean reduction among ibuprofen-treated subjects (p=0.04); and no change in the control group. IL-6 change between groups was statistically significant (p=0.024). No other inflammatory biomarker differences were observed between groups after 28 days.
  
  
  CONCLUSIONS
  Although we studied only one agent, HDI, these results suggest that one month may be inadequate to assess anti-inflammatory candidates using markers from induced sputum.
authors: Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA; Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA. Electronic address: james.chmiel@uhhospitals.org.
authors: James F
authors: JF
authors: Chmiel
authors: Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA; Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA.
authors: Michael W
authors: MW
authors: Konstan
authors: Children's Hospital Colorado and University of Colorado, 13123 East 16th Avenue, Aurora, CO 80045, USA.
authors: Frank J
authors: FJ
authors: Accurso
authors: Seattle Children's Hospital Research Institute and Cystic Fibrosis Therapeutics Development Network Coordinating Center, 2001 Eighth Avenue, Seattle, WA 98121, USA.
authors: James
authors: J
authors: Lymp
authors: Seattle Children's Hospital and University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105, USA.
authors: Nicole
authors: N
authors: Mayer-Hamblett
authors: Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106, USA.
authors: Donald R
authors: DR
authors: VanDevanter
authors: Seattle Children's Hospital and University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105, USA.
authors: Lynn M
authors: LM
authors: Rose
authors: Seattle Children's Hospital and University of Washington School of Medicine, 4800 Sand Point Way NE, Seattle, WA 98105, USA.
authors: Bonnie W
authors: BW
authors: Ramsey
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015415:Biomarkers / Q000032:analysis; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000276:immunology*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D013183:Sputum / Q000737:chemistry*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D015850:Interleukin-6; D007052:Ibuprofen
keywords: Anti-inflammatory drugs; Biomarkers; Cystic fibrosis; Ibuprofen; Induced sputum; Inflammation