title: Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies.
abstract: BACKGROUND
  Current asthma guidelines recommend treatment based on the assessment of asthma control using symptoms and lung function. Noninvasive markers are an attractive way to modify therapy since they offer improved selection of active treatment(s) based on individual response, and improved titration of treatment using markers that are better related to treatment outcomes.
  
  
  OBJECTIVE
  To review the methodological and design features of noninvasive marker studies in asthma.
  
  
  METHODS
  Systematic assessment of published randomized trials of asthma therapy guided by fraction of exhaled nitric oxide(FENO).
  
  
  RESULTS
  FENO has appeal as a marker to adjust asthma therapy since it is readily measured, gives reproducible results, and is responsive to changes in inhaled corticosteroid doses. However, the five randomised trials of FENO guided therapy have had mixed results. This may be because there are specific design and methodological issues that need to be addressed in the conduct of ASthma TReatment ALgorithm(ASTRAL) studies. There needs to be a clear dose response relationship for the active drugs used and the outcomes measured. The algorithm decision points should be based on outcomes in the population of interest rather than the range of values in healthy people, and the algorithm used needs to provide a sufficiently different result to clinical decision making in order for there to be any discernible benefit. A new metric is required to assess the algorithm performance, and the discordance:concordance(DC) ratio can assist with this.
  
  
  CONCLUSIONS
  Incorporating these design features into future FENO studies should improve the study performance and aid in obtaining a better estimate of the value of FENO guided asthma therapy.
authors.affiliation: Department of Respiratory and Sleep Medicine, Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute at John Hunter Hospital, University of Newcastle, Newcastle, Australia. peter.gibson@hnehealth.nsw.gov.au
authors.forename: P G
authors.initials: PG
authors.lastname: Gibson
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000465:Algorithms; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D016903:Drug Monitoring; D045853:Exhalation; D006801:Humans; D009569:Nitric Oxide / Q000032:analysis*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D009569:Nitric Oxide