Exhaled nitric oxide in symptomatic children at preschool age predicts later asthma

Allergy. 2013 Apr;68(4):531-8. doi: 10.1111/all.12127. Epub 2013 Feb 18.


Background: Prediction of asthma in young children with respiratory symptoms is hampered by the lack of objective measures applicable in clinical routine. In this prospective study in a preschool children cohort, we assessed whether the fraction of exhaled nitric oxide (FeNO), a biomarker of airway inflammation, is associated with asthma at school age.

Methods: At baseline, IgE and eosinophils were measured in the blood, and FeNO was measured offline in 391 children aged 3-47 months with lower airway symptoms. We developed an asthma predictive index (API) including high FeNO as major criterion. At follow-up, primary outcome was physician-diagnosed asthma based on standardized interviews in those children reaching school age (n = 166).

Results: FeNO was significantly elevated in those children with later asthma (68/166) as compared to children not developing asthma. Median (IQR) FeNO was 10.5 (6.6-17.2) vs. 7.4 (5.3-10.3) ppb. Per 5 ppb FeNO increase, the odds ratio (95% CI) for asthma increased by 2.44 (1.61-3.70) without changing when adjusting for confounders. Using the new API, children scored at risk had 58.0% probability for later asthma, whereas the negative predictive value was 78.2%, which was comparable to the classical API.

Conclusions: In this cohort of high-risk preschool children, elevated FeNO is associated with increased risk for school-age asthma. The new API including FeNO identifies children at risk of later asthma comparably to the classical API, but does not require blood sampling.

MeSH terms

  • Asthma / diagnosis*
  • Biomarkers
  • Breath Tests
  • Child, Preschool
  • Eosinophils
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin E / blood
  • Infant
  • Male
  • Nitric Oxide / analysis*
  • Odds Ratio
  • Prognosis
  • Prospective Studies
  • Respiratory Sounds


  • Biomarkers
  • Nitric Oxide
  • Immunoglobulin E