title: Exhaled nitric oxide in the diagnosis of asthma in adults: a systematic review.
abstract: OBJECTIVE
  To identify and synthesize evidence on the diagnostic accuracy ofFENO for asthma in adults.
  
  
  METHODS
  Systematic searches (nine key biomedical databases and trial registers) were carried out on November 2014. Records were included if they recruited patients with the symptoms of asthma; used a single set of inclusion criteria; measuredFENO50in accordance with American Thoracic Society guidelines, 2005 (off-line excluded); reported/allowed calculation of true-positive, true-negative, false-positive and false-negative patients as classified against any reference standard. Study quality was assessed using QUADAS II. Meta-analysis was planned where clinical study heterogeneity allowed. Rule-in and rule-out uses ofFENO were considered.
  
  
  RESULTS
  A total of 4861 records were identified originally and 1312 in an update. Twenty-seven studies were included. Heterogeneity precluded meta-analysis. Results varied even within subgroups of studies. Cut-off values for the best sum of sensitivity and specificity varied from 12 to 55 p.p.b., but did not produce high accuracy. 100% sensitivity or 100% specificity was reported by some studies indicating potential use as a rule-in or rule-out strategy.
  
  
  CONCLUSIONS
  FENO50had variable diagnostic accuracy even within subgroups of studies with similar characteristics. Diagnostic accuracy, optimal cut-off values and best position forFENO50within a pathway remain poorly evidenced.
authors.affiliation: Health Economics and Decision Science, ScHARR, University of Sheffield, Sheffield, UK.
authors.forename: S E
authors.identifier: http://orcid.org/0000-0002-9318-9206
authors.initials: SE
authors.lastname: Harnan
authors.affiliation: Health Economics and Decision Science, ScHARR, University of Sheffield, Sheffield, UK.
authors.forename: M
authors.initials: M
authors.lastname: Essat
authors.affiliation: Health Economics and Decision Science, ScHARR, University of Sheffield, Sheffield, UK.
authors.forename: T
authors.initials: T
authors.lastname: Gomersall
authors.affiliation: Health Economics and Decision Science, ScHARR, University of Sheffield, Sheffield, UK.
authors.forename: P
authors.initials: P
authors.lastname: Tappenden
authors.affiliation: Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: I
authors.initials: I
authors.lastname: Pavord
authors.affiliation: School of Paediatrics & Child Health, Princess Margaret Hospital, University of Western Australia, Crawley, WA, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Everard
authors.affiliation: Department of Respiratory Medicine, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: R
authors.initials: R
authors.lastname: Lawson
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000378:metabolism*; D015415:Biomarkers; D045853:Exhalation; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide
keywords: asthma; diagnosis; exhaled nitric oxide; meta-analysis; systematic review