摘要
该研究的目的是确定5-脂氧合酶抑制剂zileuton是否能降低哮喘患者在吸入糖皮质激素(ICS)维持治疗期间的支气管高反应性(BHR)。在一项随机、双盲、安慰剂对照、交叉研究中,挑战测试组胺(挑衅的组胺浓度生产下降20%在一秒用力呼气量(FEV1) (PC20嘘))和超声喷雾蒸馏水(UNDW)(挑衅剂量UNDW生产FEV1下降20% (PD20 UNDW))进行了七个哮喘患者摄入后的400年mg zileuton or placebo. All patients (mean age 33 yrs, mean FEV1 111% of predicted) had marked BHR, as indicated by a mean PD20,UNDW of 4.74 mL under treatment for at least 6 months with up to 800 microg ICS (mean 536 microg daily). On four different occasions, separated by at least 5 days, two UNDW and two histamine challenge tests were performed in random order 3 h after a morning dose of either zileuton or placebo. Neither zileuton nor placebo changed baseline airway calibre prior to provocation. Zileuton increased PC20,Hist from 0.99 to 5.64 mg x mL(-1) (2.1 doubling doses; p<0.03 compared to placebo), and increased PD20,UNDW from 3.10 to 9.31 mL (1.3 doubling doses; p<0.05 compared to placebo). In conclusion, a single dose of 400 mg zileuton attenuates bronchial hyperresponsiveness to histamine and ultrasonically nebulized distilled water in asthmatic patients with marked bronchial hyperresponsiveness during treatment with inhaled corticosteroids.