Exhaled nitric oxide continues to reflect airway hyperresponsiveness and disease activity in inhaled corticosteroid-treated adult asthmatic patients

Respirology. 2003 Dec;8(4):479-86. doi: 10.1046/j.1440-1843.2003.00495.x.


Objective: Exhaled nitric oxide (eNO) has been used as a surrogate of airway inflammation in mild asthma. However, whether eNO levels reflect disease activity in symptomatic asthmatics receiving moderate doses of inhaled corticosteroid (ICS) is more uncertain.

Methodology: To examine the relationship between eNO levels, sputum and blood eosinophils (SpE and PbE), PD(20) methacholine as a marker of airway hyperresponsiveness (AHR) and clinical status in 28 ICS-treated asthmatic subjects with persistent asthma compared to that in 25 symptomatic asthmatics managed with beta2-agonists alone.

Results: As expected, eNO levels were normalized in ICS-treated subjects and significantly elevated in the beta2-agonist only group (P < 0.001). SpE, PbE and PD20M did not differ between asthmatic groups but FEV1 was significantly worse in ICS-treated subjects (P < 0.01). Exhaled NO levels correlated with PbE within both asthmatic groups (P < 0.005), but with SpE only in ICS-untreated subjects (r(s) = 0.6, P < 0.05). In contrast, PD20M was negatively correlated with eNO and PbE in ICS-treated subjects only (r(s) = - 0.4, r(s) = - 0.4, respectively, P < 0.05). SpE and PbE were strongly correlated in both asthmatic groups (r(s) = 0.8, r(s) = 0.7, respectively, P < 0.005). Exhaled NO levels, SpE and PbE were all positively associated with increased nocturnal awakenings ( P < 0.05) in ICS-treated subjects, but not in ICS-untreated subjects.

Conclusions: In ICS-treated asthma, eNO reflects clinical activity, PbE and AHR but not eosinophilic airway inflammation. Exhaled NO levels are quantitatively and relationally different in asthmatic subjects treated with ICS and continue to have potential for use as a surrogate of asthma pathophysiology in this group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / pharmacology*
  • Adrenal Cortex Hormones / therapeutic use
  • Adrenergic beta-Agonists / pharmacology
  • Adult
  • Aged
  • Anti-Asthmatic Agents / pharmacology
  • Asthma / drug therapy*
  • Asthma / metabolism*
  • Beclomethasone / pharmacology
  • Biomarkers
  • Bronchial Hyperreactivity / metabolism*
  • Cross-Sectional Studies
  • Drug Monitoring
  • Eosinophils / metabolism
  • Female
  • Humans
  • Linear Models
  • Male
  • Methacholine Chloride / pharmacology
  • Middle Aged
  • Multivariate Analysis
  • Nitric Oxide / metabolism*
  • Severity of Illness Index
  • Sputum / cytology
  • Statistics, Nonparametric


  • Adrenal Cortex Hormones
  • Adrenergic beta-Agonists
  • Anti-Asthmatic Agents
  • Biomarkers
  • Methacholine Chloride
  • Nitric Oxide
  • Beclomethasone