Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, California, USA.
COPD. 2011 Feb;8(1):21-9. doi: 10.3109/15412555.2010.540273.
Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations.
We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization.
Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within 12 hours of hospital admission for COPD exacerbation. Primary outcome measure was hospital length of stay; secondary outcomes included treatment failure and biomarkers of leukotriene production.
Sixty subjects were randomized to zileuton and 59 to placebo (the study was stopped short of enrollment goals because of slow recruitment). There was no difference in hospital length of stay (3.75 +/- 2.19 vs. 3.86 +/- 3.06 days for zileuton vs. placebo, p = 0.39) or treatment failure (23% vs. 27% for zileuton vs. placebo, p = 0.63) despite a decline in urinary LTE(4) levels in the zileuton-treated group as compared to placebo at 24 hours (change in natural log-transformed ng/mg creatinine -1.38 +/- 1.19 vs. 0.14 +/- 1.51, p < 0.0001) and 72 hours (-1.32 +/- 2.08 vs. 0.26 +/- 1.93, p<0.006). Adverse events were similar in both groups.
While oral zileuton during COPD exacerbations that require hospital admission is safe and reduces urinary LTE(4) levels, we found no evidence suggesting that this intervention shortened hospital stay, with the limitation that our sample size may have been insufficient to detect a modest but potentially meaningful clinical improvement.
白三烯参与了 COPD 急性加重的发病机制，但白三烯调节剂尚未被研究作为急性加重的可能治疗方法。
我们旨在测试口服齐留通（一种 5-脂氧合酶抑制剂）联合常规治疗对需要住院治疗的 COPD 急性加重的安全性和疗效。
一项随机、双盲、安慰剂对照、平行组研究，600mg 齐留通口服，每日 4 次，共 14 天，在 COPD 加重住院后 12 小时内开始。主要终点是住院时间；次要终点包括治疗失败和白三烯产生的生物标志物。
60 名受试者被随机分配到齐留通组，59 名受试者被分配到安慰剂组（由于招募缓慢，研究提前停止）。两组住院时间无差异（齐留通组 3.75±2.19 天 vs. 安慰剂组 3.86±3.06 天，p=0.39）或治疗失败（齐留通组 23% vs. 安慰剂组 27%，p=0.63），尽管与安慰剂组相比，齐留通治疗组在 24 小时（自然对数变换后尿 LTE(4)水平变化-1.38±1.19 vs. 0.14±1.51，p<0.0001）和 72 小时（-1.32±2.08 vs. 0.26±1.93，p<0.006）时尿 LTE(4)水平下降。两组不良反应相似。
虽然口服齐留通在需要住院治疗的 COPD 急性加重期间是安全的，并且降低了尿 LTE(4)水平，但我们没有发现证据表明这种干预可以缩短住院时间，其局限性在于我们的样本量可能不足以检测到适度但可能有意义的临床改善。
