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

Author(s): Rafferty P, Ng WH, Phillips G, Clough J, Church MK, Aurich R, Ollier S, Holgate ST

Affiliation(s): Immunopharmacology Group, Medicine I and Clinical Pharmacology, Southampton General Hospital, England.

Publication date & source: 1989-11, J Allergy Clin Immunol., 84(5 Pt 1):649-57.

Publication type: Clinical Trial; Controlled Clinical Trial; Randomized Controlled Trial

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 FEV1. Plasma-histamine concentrations and FEV1 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 FEV1 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 FEV1 of greater than 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 FEV1 response time-course curves revealed that azelastine reduced the early response (first 2 hours) by 32.5% (p less than 0.05) (all subjects) and reduced the late response (2 to 8 hours) by 70.2% (p less than 0.05) (n = 5). Azelastine had no significant inhibitory effect on the early increase in plasma histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

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