Effect of azelastine on bronchoconstriction induced by histamine and leukotriene C4 in patients with extrinsic asthma.

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Abstract
Azelastine, a new oral agent with antiallergic and antihistamine properties, has been shown to inhibit the effect of histamine and leukotriene (LT) in vitro, though not a specific leukotriene receptor antagonist. The effect of both a single dose (8.8 mg) and 14 days' treatment (8.8 mg twice daily) with azelastine on bronchoconstriction induced by LTC4 and histamine has been examined in 10 patients with mild asthma in a placebo controlled, double blind, crossover study. LTC4 and histamine were inhaled in doubling concentrations from a dosimeter and the results expressed as the cumulative dose (PD) producing a 20% fall in FEV1 (PD20FEV1) and 35% fall in specific airways conductance (PD35sGaw). The single dose of azelastine produced a significantly greater FEV1 and sGaw values than placebo at 3 hours, but this bronchodilator effect was not present after 14 days of treatment. Azelastine was an effective H1 antagonist; after a single dose and 14 days' treatment with placebo the geometric mean PD20FEV1 histamine values (mumol) were 0.52 (95% confidence interval 0.14-1.83) and 0.54 (0.12-2.38), compared with 22.9 (11.5-38.3) and 15.2 (6.47-35.6) after azelastine (p less than 0.01 for both). LTC4 was on average 1000 times more potent than histamine in inducing bronchoconstriction. Azelastine did not inhibit the effect of inhaled LTC4; the geometric mean PD20FEV1 LTC4 (nmol) after a single dose and 14 days' treatment was 0.60 and 0.59 with placebo compared with 0.65 and 0.75 with azelastine. The PD35sGaw LTC4 was also unchanged at 0.66 and 0.73 for placebo compared with 0.83 and 0.74 for azelastine. Thus prolonged blockade of H1 receptors did not attenuate the response to LTC4, suggesting that histamine and LTC4 act on bronchial smooth muscle through different receptors. Four patients complained of drowsiness while taking azelastine but only one who was taking placebo and three patients complained of a bitter, metallic taste while taking azelastine.