Use of exhaled nitric oxide measurements to guide treatment in chronic asthma

N Engl J Med. 2005 May 26;352(21):2163-73. doi: 10.1056/NEJMoa043596. Epub 2005 May 24.


Background: International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FE(NO)) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.

Methods: In a single-blind, placebo-controlled trial, we randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FE(NO) measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.

Results: Forty-six patients in the FE(NO) group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 microg per day for the FE(NO) group (95 percent confidence interval, 263 to 477) and 641 microg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 microg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FE(NO) group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a nonsignificant reduction of 45.6 percent (95 percent confidence interval for mean difference, -78.6 percent to 54.5 percent) in the FE(NO) group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).

Conclusions: With the use of FE(NO) measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / administration & dosage
  • Adult
  • Aged
  • Algorithms
  • Androstadienes / administration & dosage*
  • Asthma / diagnosis*
  • Asthma / drug therapy
  • Asthma / physiopathology
  • Biomarkers / analysis
  • Breath Tests
  • Bronchodilator Agents / administration & dosage*
  • Child
  • Eosinophils
  • Female
  • Fluticasone
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Nitric Oxide / analysis*
  • Prospective Studies
  • Single-Blind Method
  • Spirometry
  • Sputum / immunology


  • Adrenal Cortex Hormones
  • Androstadienes
  • Biomarkers
  • Bronchodilator Agents
  • Nitric Oxide
  • Fluticasone