Exhaled nitric oxide following leukotriene E-4 and methacholine inhalationin 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 as thma. However, the precise mechanisms responsible of promoting increased fr action of expired nitric oxide (FENO) in asthma are unknown. As leukotriene antagonism has been shown to reduce FENO in patients with asthma, we hypot hesized that leukotrienes mediate the increased FENO encountered in this co ndition. Furthermore, because leukotriene antagonism stabilizes serum eosin ophil markers during reductions in inhaled corticosteroid doses, and FENO h as been shown to correlate with sputum eosinophils in asthma, we reasoned t hat the effect of leukotrienes on FENO might be mediated by eosinophils rec ruited 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 count s before and after bronchoprovocation. We then compared FENO in the seven s ubjects who developed increased sputum eosinophils following LTE4 inhalatio n with values measured after methacholine inhalation in these seven subject s. 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 b aseline after LTE4 inhalation was larger than that after methacholine inhal ation (+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.