title: Biomarker-based asthma phenotypes of corticosteroid response.
abstract: BACKGROUND
  Asthma is a heterogeneous disease with different phenotypes. Inhaled corticosteroid (ICS) therapy is a mainstay of treatment for asthma, but the clinical response to ICSs is variable.
  
  
  OBJECTIVE
  We hypothesized that a panel of inflammatory biomarkers (ie, fraction of exhaled nitric oxide [Feno], sputum eosinophil count, and urinary bromotyrosine [BrTyr] level) might predict steroid responsiveness.
  
  
  METHODS
  The original study from which this analysis originates comprised 2 phases: a steroid-naive phase 1 and a 28-day trial of ICSs (phase 2) during which Feno values, sputum eosinophil counts, and urinary BrTyr levels were measured. The response to ICSs was based on clinical improvements, including a 12% or greater increase in FEV1, a 0.5-point or greater decrease in Asthma Control Questionnaire score, and 2 doubling dose or greater increase in provocative concentration of adenosine 5'-monophosphate causing a 20% decrease in FEV1 (PC20AMP). Healthy control subjects were also evaluated in this study for comparison of biomarkers with those seen in asthmatic patients.
  
  
  RESULTS
  Asthmatic patients had higher than normal Feno values, sputum eosinophil counts, and urinary BrTyr levels during the steroid-naive phase and after ICS therapy. After 28-day trial of ICSs, Feno values decreased in 82% of asthmatic patients, sputum eosinophil counts decreased in 60%, and urinary BrTyr levels decreased in 58%. Each of the biomarkers at the steroid-naive phase had utility for predicting steroid responsiveness, but the combination of high Feno values and high urinary BrTyr levels had the best power (13.3-fold, P < .01) to predict a favorable response to ICS therapy. However, the magnitude of the decrease in biomarker levels was unrelated to the magnitude of clinical response to ICS therapy.
  
  
  CONCLUSIONS
  A noninvasive panel of biomarkers in steroid-naive asthmatic patients predicts clinical responsiveness to ICS therapy.
authors.affiliation: Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Cowan
authors.affiliation: Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: D Robin
authors.initials: DR
authors.lastname: Taylor
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Peterson
authors.affiliation: Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Cowan
authors.affiliation: Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Palmay
authors.affiliation: Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Avis
authors.initials: A
authors.lastname: Williamson
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Jef
authors.initials: J
authors.lastname: Hammel
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: comhais@ccf.org.
authors.forename: Suzy A A
authors.initials: SAA
authors.lastname: Comhair
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D015415:Biomarkers; D016022:Case-Control Studies; D045853:Exhalation; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D009569:Nitric Oxide; D016017:Odds Ratio; D010641:Phenotype; D011379:Prognosis; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; C475724:bromotyrosine; D009569:Nitric Oxide; D014443:Tyrosine
keywords: Asthma; biomarker; clinical outcome; fraction of exhaled nitric oxide; inhaled corticosteroids; sputum eosinophils; urinary bromotyrosine