Leukotriene E4-induced persistent eosinophilia and airway obstruction are reversed by zafirlukast in patients with asthma

Background: We have shown that inhalation of leukotriene (LT) E-4 contributes to specific recruitment of eosinophils to the airway mucosa in patients with asthma at the time of maximal decrease in airway-specific conductance. Objective: We examined the ability of the cysteinyl LT1 receptor antagonist, zafirlukast, to improve or prevent LT-mediated eosinophilia and airway obstruction in asthma. Methods: Bronchial biopsies were taken and pulmonary function was measured before and 4 to 6 hours after the dose of inhaled LTE4 causing a greater than or equal to15% fall in FEV1 at baseline both at week 0 and after 6-week randomly assigned treatment with a high dose of zafirlukast, 80 mg twice daily. Results: Leukotriene E-4 inhalation at week 0 doubled the number of eosinophils in the airway mucosa in 21 of 25 patients with mild asthma, increased the numbers of neutrophils and lymphocytes, and decreased FEV1 (-17%). Zafirlukast reduced both airway eosinophilia and obstruction in FEV1, whereas with a double-blind placebo treatment, the effect of LTE4 on both parameters persisted for 6 weeks. On repeat LTE4 inhalation challenge after 6 weeks, zafirlukast treatment prevented further airway eosinophilia and decrease in FEV1 seen in the placebo group. Conclusion: Persistent LTE4-induced airway eosinophilia may form the basis of an amplification mechanism for further eosinophil recruitment. Zafirlukast prevents LTE4-induced eosinophilic airway inflammation in mild asthma.