Relationship between neutrophil elastase and acute lung injury in humans
Relationship between neutrophil elastase and acute lung injury in humans
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DOI：
10.1016/j.pupt.2004.05.003
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发表时间：
2004-01-01
影响因子：
3.2
通讯作者：
Abiru, T
中科院分区：
文献类型：
--
作者：
Tamakuma, S;Ogawa, M;Abiru, T
我们使用选择性中性粒细胞弹性蛋白酶抑制剂西维来司他钠水合物（Sivelestat）对与全身炎症反应综合征相关的急性肺损伤（ALI）患者进行了临床试验，以研究中性粒细胞弹性蛋白酶在 ALI 中的作用。在230名患者参与的III期双盲研究（研究1）中，以肺功能改善（PFI）评级为主要终点，以机械呼吸机撤机率、重症监护病房（ICU）出院率和生存率作为次要终点来评估西维来司他的疗效。随后，对 20 名患者进行了一项非盲研究（研究 2），使用机械通气脱机程序，以无呼吸机天数 (VFD) 值（主要终点）重新评估其疗效，并与研究 1 亚组进行比较，该亚组符合研究 2 中使用的选择标准。在研究 1 中，西维来司他提高了 PFI 评级，缩短了机械通气持续时间，并缩短了在 ICU 的停留时间， 尽管对生存率没有显着效果。研究2中的VFD值与研究1亚组的最佳剂量组相当，并且VFD值的增加与PFI评级和ICU空闲天数的增加相关。结论是中性粒细胞弹性蛋白酶可能参与人类ALI的发病机制。 (C) 2004 Elsevier Ltd. 保留所有权利。
We conducted clinical trials in patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome using a selective neutrophil elastase inhibitor, sivelestat sodium hydrate (Sivelestat), to investigate the involvement of neutrophil elastase in ALI. In the phase III double-blind study (Study 1) in 230 patients, the efficacy of Sivelestat was evaluated with the pulmonary function improvement (PFI) rating as the primary endpoint, and the weaning rate from mechanical ventilator, the discharge rate from intensive care unit (ICU), and the survival rate as secondary endpoints. Afterwards, an unblinded study (Study 2) in 20 patients was conducted using procedures for weaning from mechanical ventilation to reevaluate its efficacy with ventilator-free days (VFD) value, the primary endpoint, and to compare with that of Study 1 subgroup, which met the selection criteria used in Study 2. Sivelestat increased PFI rating, reduced duration of mechanical ventilation, and shortened stay in ICU in Study 1, although there was no significant efficacy on the survival rate. VFD value in Study 2 was comparable to that in the optimal-dose group of Study 1 subgroup, and increase in VFD value correlated with PFI rating and increase in ICU free days. It was concluded that neutrophil elastase may be involved in the pathogenesis of ALI in humans. (C) 2004 Elsevier Ltd. All rights reserved.