Influence of zafirlukast and loratadine on exercise-induced bronchoconstriction

BACKGROUND: Airway obstruction induced by physical exercise is a common feature in asthma, and conventional treatments do not offer optimal protection. There is thus a need for additional therapies for optimal control of exercise-induced bronchoconstriction (EIB). OBJECTIVE: The influence of treatment with the antihistamine loratadine and the antileukotriene zafirlukast alone and in combination on EIB was investigated. This combination has previously shown beneficial additive effects in allergen-induced bronchoconstriction. METHODS: In a double-blind cross-over study loratadine (10 mg twice daily) and zafirlukast (80 mg twice daily) were evaluated alone and in combination in 16 nonsmoking patients with mild asthma, previously documented EIB, and airways hyperresponsiveness to histamine. RESULTS: The mean +/- SE maximum decrease in FEV1 after a standardized exercise provocation was 21.6% +/- 3% after placebo, 22.8% +/- 3% after loratadine, 13.9% +/- 2% after zafirlukast (P <.05 vs placebo), and 10.3% +/- 2% after the combination of loratadine and zafirlukast (P <.05 vs placebo). Expressed as the area under the FEV1 percentage change versus time curve, the mean protection produced by zafirlukast and the combination of zafirlukast and loratadine was 57% and 65%, respectively, whereas loratadine alone had no significant protective effect. There was also no significant difference between the effect of zafirlukast alone or in combination with loratadine. CONCLUSION: The study confirmed the beneficial effect of a leukotriene receptor antagonist in EIB but failed to obtain evidence that H1-receptor antagonism alone or together with the cysteinyl-leukotriene 1 receptor antagonist zafirlukast offers a protective effect.