Exhaled nitric oxide following leukotriene E4 and methacholine inhalation in patients with asthma

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 (FENO) in asthma are unknown. As leukotriene antagonism has been shown to reduce FENO in patients with asthma, we hypothesized that leukotrienes mediate the increased FENO encountered in this condition. Furthermore, because leukotriene antagonism stabilizes serum eosinophil markers during reductions in inhaled corticosteroid doses, and FENO has been shown to correlate with sputum eosinophils in asthma, we reasoned that the effect of leukotrienes on FENO 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 FENO and sputum differential counts before and after bronchoprovocation. We then compared FENO in the seven subjects who developed increased sputum eosinophils following LTE4 inhalation with values measured after methacholine inhalation in these seven subjects. Following LTE4 inhalation, eosinophils rose from 4.01 +/- 0.89% pre-LTE4 to 8.33 +/-: 1.52% post-LTE4. The mean change in sputum eosinophils from baseline after LTE4 inhalation was larger than that after methacholine inhalation (+4.31 +/- 1.25% versus -1.14 +/- 0.93%). After LTE4 inhalation, FENO levels did not differ from prechallenge baseline or from levels following methacholine inhalation (ANOVA p > 0.05). These data indicate that neither LTE4 nor recruitment of eosinophils into the airway by LTE4 is a sufficient stimulus to acutely increase FENO in subjects with asthma.