Exhaled nitric oxide following leukotriene E(4) and methacholine inhalation in patients with asthma

Am J Respir Crit Care Med. 2000 Nov;162(5):1685-9. doi: 10.1164/ajrccm.162.5.9911081.


Nitric oxide (NO) is a molecular gas that can be recovered in higher levels from the exhaled gas of subjects with asthma than from subjects without asthma. However, the precise mechanisms responsible of promoting increased fraction of expired nitric oxide (FE(NO)) in asthma are unknown. As leukotriene antagonism has been shown to reduce FE(NO) in patients with asthma, we hypothesized that leukotrienes mediate the increased FE(NO) encountered in this condition. Furthermore, because leukotriene antagonism stabilizes serum eosinophil markers during reductions in inhaled corticosteroid doses, and FE(NO) has been shown to correlate with sputum eosinophils in asthma, we reasoned that the effect of leukotrienes on FE(NO) might be mediated by eosinophils recruited to the airway by leukotrienes. To test this hypothesis, we performed methacholine and leukotriene (LT) E(4) bronchoprovocation challenges in 16 subjects with atopic asthma and measured FE(NO) and sputum differential counts before and after bronchoprovocation. We then compared FE(NO) in the seven subjects who developed increased sputum eosinophils following LTE(4) inhalation with values measured after methacholine inhalation in these seven subjects. Following LTE(4) inhalation, eosinophils rose from 4.01 +/- 0.89% pre-LTE(4) to 8.33 +/- 1.52% post-LTE(4). The mean change in sputum eosinophils from baseline after LTE(4) inhalation was larger than that after methacholine inhalation (+4.31 +/- 1.25% versus -1.14 +/- 0.93%). After LTE(4) inhalation, FE(NO) levels did not differ from prechallenge baseline or from levels following methacholine inhalation (ANOVA p > 0.05). These data indicate that neither LTE(4) nor recruitment of eosinophils into the airway by LTE(4) is a sufficient stimulus to acutely increase FE(NO) in subjects with asthma.

MeSH terms

  • Administration, Inhalation
  • Adult
  • Airway Resistance
  • Asthma / metabolism*
  • Asthma / pathology
  • Asthma / physiopathology
  • Breath Tests*
  • Bronchial Provocation Tests
  • Cell Count
  • Eosinophils
  • Female
  • Humans
  • Leukotriene E4 / administration & dosage*
  • Leukotriene E4 / pharmacology
  • Male
  • Methacholine Chloride / administration & dosage*
  • Methacholine Chloride / pharmacology
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Sputum / cytology


  • Methacholine Chloride
  • Nitric Oxide
  • Leukotriene E4