title: A systematic review of fractional exhaled nitric oxide in the routine management of childhood asthma.
abstract: BACKGROUND
  Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of eosinophilic inflammation which may be used to guide the management of asthma in childhood.
  
  
  OBJECTIVE
  To synthesise the available evidence on the efficacy of FeNO-guided management of childhood asthma.
  
  
  METHODS
  Databases including MEDLINE and the Cochrane Library were searched, and randomised controlled trials (RCTs) comparing FeNO-guided management with any other monitoring strategy were included. Study quality was assessed using the Cochrane risk of bias tool for RCTs, and a number of outcomes were examined, including: exacerbations, medication use, quality of life, adverse events, and other markers of asthma control. Meta-analyses were planned if multiple studies with suitable heterogeneity were available. However, due to wide variations in study characteristics, meta-analysis was not possible.
  
  
  RESULTS
  Seven RCTs were identified. There was some evidence that FeNO-guided monitoring results in improved asthma control during the first year of management, although few results attained statistical significance. The impact on severe exacerbations was unclear. Similarly, the impact on use of anti-asthmatic drugs was unclear, and appears to depend on the step up/down protocols, and the clinical characteristics of patients.
  
  
  CONCLUSIONS
  The potential benefit of FeNO monitoring is equivocal. Trends toward reduced exacerbation and increased medication use were seen, but typically failed to reach statistical significance. There are a number of issues that complicate data interpretation, including differences in the likely severity of included cohorts and variations in treatment algorithms. Further work is needed to systematically explore the impact of these parameters.
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Gomersal
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Sue
authors.initials: S
authors.lastname: Harnan
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Munira
authors.initials: M
authors.lastname: Essat
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Tappenden
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Wong
authors.affiliation: Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom.
authors.forename: Rod
authors.initials: R
authors.lastname: Lawson
authors.affiliation: University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Pavord
authors.affiliation: School of Paediatrics and Child Health, Princess Margaret Hospital, Respiratory Medicine, University of Western Australia, Crawley, Australia.
authors.forename: Mark Lloyd
authors.initials: ML
authors.lastname: Everard
mesh_terms: D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests; D002648:Child; D019468:Disease Management; D045853:Exhalation; D006801:Humans; D009569:Nitric Oxide / Q000032:analysis*; D011788:Quality of Life
chemical_list: D018927:Anti-Asthmatic Agents; D015415:Biomarkers; D009569:Nitric Oxide
keywords: allergy; asthma and early wheeze; biomarkers; evidence-based medicine and outcomes; nitric oxide (NO)