A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD
A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD
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DOI：
10.1378/chest.122.1.289
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发表时间：
2002-07-01
期刊：
影响因子：
9.6
通讯作者：
Stockley, RA
中科院分区：
文献类型：
--
作者：
Gompertz, S;Stockley, RA
研究目的：COPD患者典型地具有嗜中性支气管炎症和升高的中性粒细胞趋化物白三烯B-4（LTB 4）的气道浓度。进行了一项小型II期试验，以评估白三烯合成抑制剂对稳定期COPD患者支气管炎症的影响。设计：一项随机、双盲、安慰剂对照、平行组研究。设置：一所大学医院的呼吸内科。患者和干预：17例慢性支气管炎和COPD患者（平均FEV 1，35.5%预测值; SD，14.8%预测值）随机接受14天口服白三烯合成抑制剂BAYx 1005（500 mg bid）或安慰剂。测量和结果：在基线和治疗结束时获得的自发痰样品测定LTB 4、髓过氧化物酶（中性粒细胞数目和/或活化的间接标志物）和趋化活性（Boyden室）。14天后，两个治疗组之间的绝对LTB 4浓度没有显著差异（p > 0.05）。然而，BAYx 1005处理产生了显著更大的LTB 4中值降低，为-3.1 nM（四分位距[IQR]，-9.6至-0.2 nM）vs 3.0 nM（IQR，-0.3至8.5 nM）[p = 0.001]，浓度从8.0 nM开始降低基线时的IQR（4.3 - 24.4 nM）至治疗结束时的4.2 nM（IQR，1.9 - 11.9 nM）（p = 0.03）。安慰剂组无变化，两个治疗组之间的痰液髓过氧化物酶浓度或趋化性无差异（p > 0.05）。结论：这项小型研究表明，白三烯合成抑制剂可以适度降低COPD患者中性粒细胞支气管炎症的某些指标。这类抗炎药需要在大量患者中进行进一步研究，以确定临床获益。
Study objective: Patients with COPD classically have neutrophilic bronchial inflammation and raised airway concentrations of the neutrophil chemoattractant leukotriene B-4 (LTB4). A small phase II trial was conducted to assess the effects of a leukotriene synthesis inhibitor on bronchial inflammation in patients with stable COPD.Design: A randomized, double-blind, placebo-controlled, parallel-group study.Setting: Respiratory medicine department of a university hospital.Patients and intervention: Seventeen patients with chronic bronchitis and COPD (mean FEV1, 35.5% predicted; SD, 14.8% predicted) were randomized to receive 14 days of the oral leukotriene synthesis inhibitor BAYx1005 (500 mg bid) or placebo.Measurements and results: Spontaneous sputum samples obtained at baseline and at the end of treatment were assayed for LTB4, myeloperoxidase (an indirect marker of neutrophil numbers and/or activation), and chemotactic activity (Boyden chamber). After 14 days, there were no significant differences (p > 0.05) in absolute LTB4 concentrations between the two treatment groups. However, BAYx1005 treatment produced a significantly greater median reduction in LTB4 of - 3.1 nM (interquartile range [IQR], - 9.6 to - 0.2 nM) vs 3.0 nM (IQR, - 0.3 to 8.5 nM) [p = 0.001], with concentrations decreasing from 8.0 nM (IQR, 4.3 to 24.4 nM) at baseline to 4.2 nM (IQR, 1.9 to 11.9 nM) at the end of treatment (p = 0.03). There were no changes in the placebo group and no differences in sputum myeloperoxidase concentration or chemotaxis between the two treatment arms (p > 0.05).Conclusions: This small study suggests that a leukotriene synthesis inhibitor can produce modest reductions in some measures of neutrophilic bronchial inflammation in patients with COPD. This class of anti-inflammatory agent requires further study in larger numbers of patients to determine clinical benefit.