INHIBITION OF EXERCISE-INDUCED BRONCHOCONSTRICTION BY MK-571, A POTENT LEUKOTRIENE-D4 RECEPTOR ANTAGONIST
INHIBITION OF EXERCISE-INDUCED BRONCHOCONSTRICTION BY MK-571, A POTENT LEUKOTRIENE-D4 RECEPTOR ANTAGONIST
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DOI：
10.1056/nejm199012203232504
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发表时间：
1990-12-20
影响因子：
158.5
通讯作者：
OBYRNE, PM
中科院分区：
文献类型：
--
作者：
MANNING, PJ;WATSON, RM;OBYRNE, PM
背景资料：运动是哮喘患者支气管收缩的常见刺激，吸入硫肽白三烯D4（LTD 4）后也会发生支气管收缩。本研究的目的是探讨LTD 4作为运动诱导支气管收缩的介质的重要性。研究方法：在一项双盲、随机、交叉研究中，12名稳定型哮喘受试者在两次挑战前20分钟接受MK-571（160 mg）、选择性强效LTD 4受体拮抗剂或安慰剂静脉给药，两次挑战涉及先前证明可导致1秒用力呼气量（FEV 1）下降至少20%的运动水平。这两次运动挑战相隔一周。挑战的结果表示为运动后FEV 1的最大下降和从支气管收缩恢复的时间。结果：MK-571治疗减弱了所有受试者的运动诱导的支气管收缩。平均值（.+-. SEM）运动后FEV 1的最大百分比降低为25.2 ± 0.001。3.5%，服用安慰剂的受试者为9.2 . ±. 2.5 MK-571治疗组的阳性率为100%（P < 0.001）。整个组的平均抑制百分比为69.5%。运动后恢复的平均时间为33.4 ±。4.0安慰剂组为8.4 ± 1.5分钟，2.5 MK-571组与对照组比较差异有显著性（P < 0.001）。结论：这项研究表明，预处理与一个有效的和选择性的LTD 4拮抗剂显着减弱运动引起的支气管收缩，它表明，LTD 4是这种类型的支气管收缩的主要介质。
Background: Exercise is common stimulus of bronchoconstriction in subjects with asthma, who also have bronchoconstriction after inhaling the sulfidopeptide leukotriene D4 (LTD4). The purpose of this study was to investigate the importance of LTD4 as a mediator of exercise-induced bronchonstriction. Methods: In a double-blind, randomized, crossover study, 12 subjects with stable asthma were treated intravenously with MK-571 (160 mg), selective and potent LTD4-receptor antagonist, or placebo, 20 minutes before each of two challenges involving exercise at a level previously demonstrated to cause a fall of at least 20 percent in the forced expiratory volume in one second (FEV1). The two exercise challenges were separated by one week. The results of the challenges were expressed as both the maximal fall in FEV1 after exercise and the time to recovery from bronchoconstriction. Results: Treatment with MK-571 attenuated exercise-induced bronchoconstriction in all the subjects. The mean (.+-. SEM) maximal percent decrease in FEV1 after exercise was 25.2 .+-. 3.5 percent in the subjects taking placebo and 9.2 .+-. 2.5 percent in the subjects taking MK-571 (P < 0.001). The mean percent inhibition for the entire group was 69.5 percent. The mean time to recovery after exercise was 33.4 .+-. 4.0 minutes in the placebo group and 8.4 .+-. 2.5 minutes in the MK-571 group (P < 0.001). Conclusions: This study demonstrates that pretreatment with a potent and selective LTD4 antagonist markedly attenuates exercise-induced bronchoconstriction, and it suggests that LTD4 is a major mediator of this type of bronchoconstriction.