Makker H K, Lau L C, Thomson H W, Binks S M, Holgate S T
Immunopharmacology Group, University of Southampton, Southampton General Hospital, United Kingdom.
Am Rev Respir Dis. 1993 Jun;147(6 Pt 1):1413-8. doi: 10.1164/ajrccm/147.6_Pt_1.1413.
Leukotrienes are potent bronchoconstrictors, and they are present in the airways of asthmatic subjects. Leukotriene receptor antagonists given intravenously or orally prior to exercise attenuate the bronchoconstrictor response to exercise in asthma. We have determined the prophylactic effect of an inhaled leukotriene D4-receptor antagonist ICI 204,219 (400 micrograms) against exercise-induced bronchoconstriction in nine asthmatic subjects in a randomized, placebo-controlled, double-blind, cross-over study. Exercise challenge was performed on a cycle ergometer at a predetermined work load that was kept constant throughout the study. A "screening" and a "run-in" exercise test were performed to determine the reproducibility of the challenge. ICI 204,219 or matched placebo was given 30 min prior to exercise challenge, and bronchoconstriction after exercise was assessed as change in FEV1 over 30 min. There was no significant effect on baseline airway caliber at 20 min after inhalation of ICI 204,219. ICI 204,219 significantly inhibited the bronchoconstrictor response to exercise. The mean maximal percentage fall in FEV1 after exercise was 14.5% as compared with the placebo of 30.2% (p = 0.043), and the area under curve (AUC) for FEV1 during the first 30 min (AUC0-30) after exercise was significantly reduced (p = 0.043). The time for recovery of FEV1 to 5% of baseline was also significantly shorter with ICI 204,219 than with placebo (median, 20 versus 60 min; p = 0.018). The protection against exercise-induced bronchoconstriction provided by ICI 204,219 was variable, with almost complete inhibition of the response in three subjects, partial inhibition in another three subjects, and no protection in three subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
白三烯是强效支气管收缩剂，存在于哮喘患者的气道中。运动前静脉注射或口服白三烯受体拮抗剂可减轻哮喘患者运动引起的支气管收缩反应。我们在一项随机、安慰剂对照、双盲、交叉研究中，确定了吸入性白三烯D4受体拮抗剂ICI 204,219（400微克）对9名哮喘患者运动诱发支气管收缩的预防作用。运动激发试验在自行车测力计上进行，在预定的工作负荷下进行，该负荷在整个研究过程中保持恒定。进行“筛查”和“预试验”运动试验以确定激发试验的可重复性。在运动激发试验前30分钟给予ICI 204,219或匹配的安慰剂，并将运动后支气管收缩评估为30分钟内FEV1的变化。吸入ICI 204,219后20分钟对基线气道口径无显著影响。ICI 204,219显著抑制运动引起的支气管收缩反应。运动后FEV1的平均最大下降百分比为14.5%，而安慰剂组为30.2%（p = 0.043），运动后前30分钟（AUC0-30）FEV1的曲线下面积（AUC）显著降低（p = 0.043）。与安慰剂相比，ICI 204,219使FEV1恢复到基线的5%所需的时间也显著缩短（中位数，20分钟对60分钟；p = 0.018）。ICI 204,219对运动诱发支气管收缩的保护作用存在差异，三名受试者的反应几乎完全被抑制，另外三名受试者部分被抑制，三名受试者无保护作用。（摘要截短于250字）
