title: Exhaled nitric oxide discriminates children with and without allergic sensitization in a population-based study.
abstract: BACKGROUND
  Fraction of exhaled nitric oxide (FeNO) as a biomarker of airway inflammation in children warrants better clarification.
  
  
  OBJECTIVE
  To identify the determinants of FeNO in children and assess the validity of FeNO as a discriminative tool for asthma, rhinitis or allergic sensitization in a population setting.
  
  
  METHODS
  Children aged 5-18 years (N=1717) were evaluated using online FeNO measurements, questionnaires, anthropometric measurements, pulmonary function tests and total and specific serum IgE.
  
  
  RESULTS
  FeNO levels were age-dependent, with an average increase of 7.4% per year of age. It decreased with increasing body mass index (BMI), estimated at 1.5% decrease per kg/m(2) . Children with allergic sensitization had elevated FeNO independent of allergic symptoms. In the combined analyses of asthma, rhinitis and allergic sensitization, elevated FeNO levels were confined mainly to children having allergic sensitization. After adjusting for allergic sensitization, a significant association between rhinitis and FeNO remained, but no such association was seen with asthma. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of FeNO at the optimum cut-off of 28 p.p.b. for diagnosing asthma were 64.3%, 69.9%, 8.8%, and 97.7%, respectively (area under the ROC curve [AUC] 0.67), and were slightly better for diagnosing allergic asthma: 70.0%, 70.4%, 9.0%, 98.3%, respectively (AUC 0.71). FeNO had modest accuracy in discriminating rhinitis with an AUC value of 0.70, and performed better in discriminating allergic rhinitis (AUC 0.78). FeNO was a robust discriminator of allergic sensitization independent of symptoms at a cut-off of 15.4 p.p.b. (AUC 0.80; sensitivity 72.2%; specificity 71.2%; PPV 76.9%; NPV 65.8%).
  
  
  CONCLUSIONS
  FeNO measurement discriminates children with and without allergic sensitization independent of allergic symptoms. On the other hand, low FeNO levels in children may help exclude allergic asthma but high levels may be caused by allergic sensitization, older age, rhinitis, and lower BMI, in addition to asthma.
authors.affiliation: Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan. yao@adm.cgmh.org.tw
authors.forename: T-C
authors.initials: TC
authors.lastname: Yao
authors.forename: L-S
authors.initials: LS
authors.lastname: Ou
authors.forename: W-I
authors.initials: WI
authors.lastname: Lee
authors.forename: K-W
authors.initials: KW
authors.lastname: Yeh
authors.forename: L-C
authors.initials: LC
authors.lastname: Chen
authors.forename: J-L
authors.initials: JL
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000367:Age Factors; D019540:Area Under Curve; D001249:Asthma / Q000175:diagnosis; D015415:Biomarkers / Q000032:analysis; D001944:Breath Tests / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D045853:Exhalation; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis*; D008297:Male; D009569:Nitric Oxide / Q000032:analysis*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012129:Respiratory Function Tests / Q000379:methods
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide