Am. J. Respir. Crit. Care Med., Volume 162, Number 5, November 2000, 1685-1689

Exhaled Nitric Oxide following Leukotriene E₄ and Methacholine Inhalation in Patients with Asthma

AARON DEYKIN, OLGA BELOSTOTSKY, CHRISTOPHER HONG, ANTHONY F. MASSARO, CRAIG M. LILLY, and ELLIOT ISRAEL

Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

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) E₄ 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 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, FE_NO 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 FE_NO in subjects with asthma.

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