Dekhuijzen P N, Bootsma G P, Wielders P L, van den Berg L R, Festen J, van Herwaarden C L
Dept of Pulmonary Diseases, Academic Hospital Nijmegen, The Netherlands.
Eur Respir J. 1997 Dec;10(12):2749-53. doi: 10.1183/09031936.97.10122749.
The aim of the study was to determine whether zileuton, an inhibitor of 5-lipoxygenase, attenuated bronchial hyperresponsiveness (BHR) in asthmatic subjects who had marked BHR during maintenance treatment with inhaled corticosteroids (ICS). In a randomized, double-blind, placebo-controlled, cross-over study, a challenge test with histamine (provocative concentration of histamine producing a 20% fall in forced expiratory volume in one second (FEV1) (PC20,Hist)) and with ultrasonically nebulized distilled water (UNDW) (provocative dose of UNDW producing a 20% fall in FEV1 (PD20,UNDW)) was performed in seven patients with asthma after intake of either 400 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.
本研究的目的是确定5-脂氧合酶抑制剂齐留通是否能减轻在吸入糖皮质激素（ICS）维持治疗期间有明显支气管高反应性（BHR）的哮喘患者的BHR。在一项随机、双盲、安慰剂对照、交叉研究中，对7例哮喘患者在服用400 mg齐留通或安慰剂后，进行了组胺激发试验（使一秒用力呼气量（FEV1）下降20%的组胺激发浓度（PC20,Hist））和超声雾化蒸馏水（UNDW）激发试验（使FEV1下降20%的UNDW激发剂量（PD20,UNDW））。所有患者（平均年龄33岁，平均FEV1为预测值的111%）均有明显的BHR，在接受高达800 μg ICS（平均每日536 μg）治疗至少6个月时，平均PD20,UNDW为4.74 mL。在四个不同的时间点，间隔至少5天，在早晨服用齐留通或安慰剂3小时后，随机顺序进行两次UNDW和两次组胺激发试验。在激发前，齐留通和安慰剂均未改变基线气道口径。齐留通使PC20,Hist从0.99增加至5.64 mg·mL-1（增加2.1倍剂量；与安慰剂相比，p<0.03），并使PD20,UNDW从3.10增加至9.31 mL（增加1.3倍剂量；与安慰剂相比，p<0.05）。总之，单剂量400 mg齐留通可减轻在吸入糖皮质激素治疗期间有明显支气管高反应性的哮喘患者对组胺和超声雾化蒸馏水的支气管高反应性。
