We have shown that inhalation of leukotriene (LT) E₄ contributes to specific recruitment of eosinophils to the airway mucosa in patients with asthma at the time of maximal decrease in airway-specific conductance.

We examined the ability of the cysteinyl LT₁ receptor antagonist, zafirlukast, to improve or prevent LT-mediated eosinophilia and airway obstruction in asthma.

Bronchial biopsies were taken and pulmonary function was measured before and 4 to 6 hours after the dose of inhaled LTE₄ causing a ≥15% 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.

Leukotriene E₄ 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.

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.