Effect of a Leukotriene Antagonist, LY171883, on Cold Air-induced Bronchoconstriction in Asthmatics

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Abstract
Isocapnic hyperpnea (ISH) of cold air induces bronchoconstriction in many asthmatic subjects. Although this response is well described, it is unclear whether this bronchoconstriction is related to the release of bronchoactive mediators. We examined whether pretretment with LY171883, a competitive antagonist of leukotreiene D4 activity via LTD4, receptors, reduced the bronchospastic response to cold air ISH in asthmatics using a randomized, double-blind, two-phase crossover design. In 20 subjects, 2 wk of treatment with either LY171883 600 mg twice a deay or placebo did not result in a change in FEV1 (3.45 .+-. 0.21 L placebo versus 3.59 .+-. 0.20 LY171883; p > 0.05). Nineteen subjects underwent cold-air ISH; LY171883 increased the geometric mean respiratory heat loss required to reduce the FEV, by 20% (PD20RHE) from 1.00 kcal/min with placebo to 1.24 kcal/min with LY171883 (p < 0.05). A similar difference was noted when response were expressed as a function of minute ventilation. LY171883 produced greater shifts in the PD20RHE in more reactive subjects (r = 0.69, p < 0.002). Among 11 different symptom scores recorded by 18 subjects, there was a singificant decrease in daytime chest tightness LY171883 (p < 0.03). The increased in PD20RHE while the subjects received LY171883 is a consistent with the hypothesis that LTD4 becomes available during cold-air ISH and may mediate bronchoconstriction. The small magnitude of the effect on the PD20PH may be due to the role of other mediates in cold-air-induced bronchoconstriction or, alternatively, to an inadequate blockade of LTD4 effects.