Predicting corticosteroid response in chronic obstructive pulmonary disease using exhaled nitric oxide

Am J Respir Crit Care Med. 2009 Nov 1;180(9):846-52. doi: 10.1164/rccm.200905-0685OC. Epub 2009 Aug 6.


Rationale: Predicting corticosteroid response in COPD is important but difficult. Response is more likely to occur in association with eosinophilic airway inflammation, for which the fraction of exhaled nitric oxide (Fe(NO)) is a good surrogate marker.

Objectives: We aimed to establish whether Fe(NO) levels would predict the clinical response to oral corticosteroid in COPD.

Methods: We performed a double-blind, crossover trial of steroid in patients with COPD. After a 4-week washout of inhaled steroids, patients received prednisone 30 mg/d or matching placebo, in random order, with an intervening 4-week washout. The predictive values of Fe(NO) for clinically significant changes in 6-minute-walk distance (6MWD), spirometry (FEV(1)), and St. George's Respiratory Questionnaire (SGRQ) were calculated.

Measurements and main results: A total of 65 patients (mean FEV(1) = 57% predicted) were randomized. With prednisone, there was a net increase of 13 m in 6MWD (P = 0.02) and 0.06 L in postbronchodilator FEV(1) (P = 0.02) compared with placebo. The change in SGRQ was not significant. Using receiver operator characteristic analysis, the area under the curve for an increase of 0.2 L in FEV(1) was 0.69 (P = 0.04) with an optimum Fe(NO) cut-point of 50 ppb. The positive and negative predictive values were 67 and 82%, respectively. FE(NO) was not a significant predictor for changes in 6MWD or SGRQ.

Conclusions: Fe(NO) is a weak predictor of short-term response to oral corticosteroid in COPD, its usefulness being limited to predicting increase in FEV(1). Clinical trial registered with (ACTRN12605000683639).

Publication types

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

MeSH terms

  • Administration, Oral
  • Adrenal Cortex Hormones / metabolism
  • Adrenal Cortex Hormones / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Exercise Tolerance / drug effects
  • Exhalation*
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Predictive Value of Tests
  • Prednisone / metabolism
  • Prednisone / therapeutic use*
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Quality of Life
  • Respiratory Function Tests
  • Treatment Outcome
  • Walking


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