The inhibitory actions of azelastine hydrochloride on the early and late bronchoconstrictor responses to inhaled allergen in atopic asthma

Abstract

We have examined the effect of azelastine hydrochloride, 8.8 mg, on the early and late responses to inhaled allergen in a group of 12 atopic subjects with asthma. On two separate days, 3 weeks apart, patients were administered either oral azelastine, 8.8 mg, or matched placebo. Four hours later they inhaled via nebulizer, a dose of allergen (grass pollen or Dermatophagoides pteronyssinus) that had previously been demonstrated to produce a 25% fall in FEV 1. Plasma-histamine concentrations and FEV 1 levels were measured at intervals during the subsequent 8 hours. After placebo, allergen inhalation produced rapid bronchoconstriction in all subjects with a maximum mean fall in FEV 1 at 30 minutes of 22.8 ± 3.4% from the postsaline baseline value. Five subjects also developed a late bronchoconstriction response with a fall in FEV 1 of >15% from postsaline baseline value between 2 and 8 hours after challenge. Azelastine reduced the bronchoconstrictor response during the first 10 minutes and produced a maximum mean fall at 30 minutes of 21.2 ± 4.4% from the postsaline baseline value. Azelastine had a marked inhibitory effect, reducing the maximum mean fall from 23.9 ± 6.3% to 9.6 ± 3.9% from the postsaline baseline value. Analysis of the area under the FEV, response time-course curves revealed that azelastine reduced the early response (first 2 hours) by 32.5% ( p < 0.05) (all subjects) and reduced the late response (2 to 8 hours) by 70.2% ( p < 0.05) (n = 5). Azelastine had no significant inhibitory effect on the early increase in plasma histamine. We conclude that azelastine significantly inhibits the late reaction to inhaled allergen and that this effect may be related to its known inhibitory actions against leukocyte activation and mediator responses.