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Summary

To study the effect of azelastine on the immediate reaction to nasal allergen challenge, we performed a double blind, placebo-controlled cross-over clinical trial. Thirteen subjects with seasonal allergic rhinitis underwent nasal challenge with antigen 4 hr after a single oral 2 mg dose of azelastine. The response was monitored by counting the number of sneezes and by measuring the levels of histamine, prostaglandin D2, immunoreactive sulphidopeptide leukotrienes, kinins and TAME-esterase activity in recovered nasal lavages. After a single dose of azelastine, there was a significant reduction in sneezing (10 vs 2, P= 0.01) and in the median levels of recovered TAME-esterase activity (63.1 vs 17.5 c.p.m. × 10-3, P= 0.01), immunoreactive sulphidopeptide leukotrienes (7.5 vs 2.1 ng/ml, P= 0.03) and kinins (1370 vs 251 pg/ml, P= 0.03), with no significant reduction in the median levels of histamine (3.7 vs 1.2 ng/ml, P= 0.2) and prostaglandin D2 (70 vs 70 pg/ml, P= 0.2) compared to placebo (numbers represent total increase over diluent challenge). These results suggest that azelastine does not inhibit mast cell activation but affects the consequences of released histamine, namely sneezing, increased vascular permeability and the generation of kinins. The results further suggest that other cells, in addition to mast cells, might be responsible for the generation of leukotrienes during the early allergic response, and that azelastine reduces their ability to generate this mediator or that inhibition of leukotriene release from mast cells occurs at lower drug concentrations.