The use of exhaled nitric oxide to guide asthma management: a randomized controlled trial

Am J Respir Crit Care Med. 2007 Aug 1;176(3):231-7. doi: 10.1164/rccm.200610-1427OC. Epub 2007 May 11.


Rationale: Current asthma guidelines recommend adjusting antiinflammatory treatment on the basis of the results of lung function tests and symptom assessment, neither of which are closely associated with airway inflammation.

Objectives: We tested the hypothesis that titrating corticosteroid dose using the concentration of exhaled nitric oxide in exhaled breath (Fe(NO)) results in fewer asthma exacerbations and more efficient use of corticosteroids, when compared with traditional management.

Methods: One hundred eighteen participants with a primary care diagnosis of asthma were randomized to a single-blind trial of corticosteroid therapy based on either Fe(NO) measurements (n = 58) or British Thoracic Society guidelines (n = 60). Participants were assessed monthly for 4 months and then every 2 months for a further 8 months. The primary outcome was the number of severe asthma exacerbations. Analyses were by intention to treat.

Measurements and main results: The estimated mean (SD) exacerbation frequency was 0.33 per patient per year (0.69) in the Fe(NO) group and 0.42 (0.79) in the control group (mean difference, -21%; 95% confidence interval [CI], -57 to 43%; p = 0.43). Overall the Fe(NO) group used 11% more inhaled corticosteroid (95% CI, -17 to 42%; p = 0.40), although the final daily dose of inhaled corticosteroid was lower in the Fe(NO) group (557 vs. 895 microg; mean difference, 338 microg; 95% CI, -640 to -37; p = 0.028).

Conclusions: An asthma treatment strategy based on the measurement of exhaled nitric oxide did not result in a large reduction in asthma exacerbations or in the total amount of inhaled corticosteroid therapy used over 12 mo, when compared with current asthma guidelines. Clinical trial registered with (ISRCTN08067387).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / administration & dosage*
  • Adult
  • Aged
  • Anti-Inflammatory Agents / administration & dosage*
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Biomarkers / analysis
  • Breath Tests / methods
  • Dose-Response Relationship, Drug
  • Eosinophils / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / analysis*
  • Nitric Oxide / metabolism
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Biomarkers
  • Nitric Oxide

Associated data

  • ISRCTN/ISRCTN08067387