THE EFFECT OF INHIBITION OF 5-LIPOXYGENASE BY ZILEUTON IN MILD-TO-MODERATE ASTHMA
THE EFFECT OF INHIBITION OF 5-LIPOXYGENASE BY ZILEUTON IN MILD-TO-MODERATE ASTHMA
复制标题
DOI：
10.7326/0003-4819-119-11-199312010-00001
复制
发表时间：
1993-12-01
影响因子：
39.2
通讯作者：
DRAZEN, JM
中科院分区：
文献类型：
--
作者：
ISRAEL, E;RUBIN, P;DRAZEN, JM
目的：评价5-脂氧合酶抑制剂齐鲁通抑制花生四烯酸5-脂氧合酶产物形成的疗效。设计：随机、双盲、安慰剂对照研究。地点：大学医院、私人过敏和肺部实践。患者：139例哮喘患者，1秒用力呼气量(FEV1)为预测值的40%~75%，且未接受吸入或口服类固醇治疗。干预：齐鲁通，2.4g/d或1.6g/d，或安慰剂治疗4周。测量：呼吸道功能、β-受体激动剂的使用和症状；结果：齐留通在给药后1小时内使FEV1增加0.35-L(95%CI，0.25%至0.45%L)(与安慰剂相比P<；0.001)，相当于较基线增加14.6%。经过4周的齐留通治疗后，患者的呼吸道功能和症状得到了改善，其中2.4g/d组的改善最大：这组患者的FEV1增加了0.32 L(CI，0.16至0.48 L)，增加了13.4%，而服用安慰剂的患者的FEV1增加了0.05-L(CI，-0.10至0.20 L)(P=0.02)。与安慰剂组相比，2.4g/d组和1.6g/d组的平均尿LTE_4水平分别降低了39.2pg/mg肌酐(CI，18.1~60.4pg/mg肌酐)和26.5pg/mg肌酐(CI，6.6~46.5pg/mg肌酐)，与安慰剂组相比略有增加(P=0.007和P=0.05)。结论：抑制5-脂氧合酶可改善哮喘患者的呼吸道功能，减少症状和用药，提示抑制5-脂氧合酶治疗哮喘是一种有效的治疗方法。此外，5-脂氧合酶产物可能在轻中度哮喘患者的部分基线气道阻塞中起调节作用。
Objective: To evaluate the effectiveness of inhibiting the formation of the 5-lipoxygenase products of arachidonic acid by the 5-lipoxygenase inhibitor zileuton in the treatment of mild-to-moderate asthma.Design: Randomized, double-blind, placebo-controlled study.Setting: University hospitals and private allergy and pulmonary practices.Patients: A total of 139 persons with asthma who had a forced expiratory volume in 1 second (FEV1) of 40% to 75% of the predicted value and who were not being treated with inhaled or oral steroids.Intervention: Zileuton, 2.4 g/d or 1.6 g/d, or placebo for 4 weeks.Measurements: Airway function, beta-agonist use, and symptoms; inhibition of 5-lipoxygenase assessed by measurement of urinary leukotriene E4 (LTE4).Results: Zileuton produced a 0.35-L (95% CI, 0.25 to 0.45 L) increase in the FEV1 within 1 hour of administration (P < 0.001 compared with placebo), equivalent to a 14.6% increase from baseline. After 4 weeks of zileuton therapy, airway function and symptoms improved, with the greatest improvements occurring in the 2.4 g/d group: This group's FEV1 increased by 0.32 L (CI, 0.16 to 0.48 L), a 13.4% increase, compared with a 0.05-L (CI, -0.10 to 0.20 L) increase in patients taking placebo (P = 0.02). Symptoms and frequency of beta-agonist use also decreased with zileuton, 2.4 g/d. The mean urinary LTE4 level decreased by 39.2 pg/mg creatinine (CI, 18.1 to 60.4 pg/mg creatinine) and 26.5 pg/mg creatinine (CI, 6.6 to 46.5 pg/mg creatinine) in the 2.4 g/d and 1.6 g/d groups, respectively, compared with a slight increase in the placebo group (P = 0.007 and P = 0.05). No difference was noted in the number of adverse events among treatment groups.Conclusions: Inhibition of 5-lipoxygenase can improve airway function and decrease symptoms and medication use in patients with asthma, suggesting that this inhibition can be useful therapy for asthma. Also, 5-lipoxygenase products may mediate part of the baseline airway obstruction in patients with mild-to-moderate asthma.