The effect of H1-receptor blockade on the development of early- and late-phase bronchoconstriction and increased bronchial responsiveness in allergen-induced asthma

Abstract

Background: Allergen challenge of subjects with asthma produces an early asthmatic response, late asthmatic response, and increases bronchial responsiveness. Histamine partly mediates the early asthmatic response, and may play a role in late-phase responses. Azelastine has antiallergic properties and has been proposed as a treatment for asthma. We therefore investigated the contribution of histamine to late-phase responses with the use of the potent H1-receptor antagonist azelastine.

Methods: Ten subjects with atopic asthma were studied in a double-blind, randomized, placebo-controlled trial. Azelastine was administered over 4 days before allergen challenge. Changes in airway caliber were followed with measurements of forced expiratory volume in 1 second, and changes in bronchial responsiveness were followed by methacholine and prostaglandin D2 bronchial provocation tests.

Results: Azelastine significantly inhibited the development of the early asthmatic response. Azelastine had no effect on the late asthmatic response or on the development of allergen-induced increases in bronchial responsiveness. The power of the study was sufficient to have had a high probability of detecting any important differences between placebo and azelastine during the late phase.

Conclusions: Azelastine had no significant effect on the late-phase response model of asthma. This study does not support the hypothesis that histamine is an important mediator of the late asthmatic response or allergen-induced increases in bronchial responsiveness.