Relationship between neutrophil elastase and acute lung injury in humans

被引:157
作者
Tamakuma, S
Ogawa, M
Aikawa, N
Kubota, T
Hirasawa, H
Ishizaka, A
Taenaka, N
Hamada, C
Matsuoka, S
Abiru, T
机构
[1] Ono Pharmaceut Co Ltd, Dev Headquarters, Chuo Ku, Osaka 5418564, Japan
[2] Ono Pharmaceut Co Ltd, Regulatory Data Management, Chuo Ku, Osaka 5418564, Japan
[3] Tokyo Univ Sci, Fac Engn, Shinjuku Ku, Tokyo 1628601, Japan
[4] Osaka Univ Hosp, Intens Care Unit, Suita, Osaka 5650871, Japan
[5] Tokyo Elect Power Co Hosp, Cent Lab, Shinjuku Ku, Tokyo 1600016, Japan
[6] Chiba Univ, Sch Med, Dept Emergency & Crit Care Med, Chuo Ku, Chiba 2608677, Japan
[7] Doju Kai Yuki Hosp, Yuki, Ibaraki 3070001, Japan
[8] Keio Univ, Dept Emergency & Crit Care Med, Shinjuku Ku, Tokyo 1608582, Japan
[9] Kumamoto Univ, Sch Med, Dept Surg 2, Kumamoto 8608556, Japan
[10] Natl Def Med Coll, Tokorozawa, Saitama 3590042, Japan
关键词
selective neutrophil elastase inhibitor; sivelestat sodium hydrate; acute lung injury; acute respiratory distress syndrome; systemic inflammatory response syndrome;
D O I
10.1016/j.pupt.2004.05.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:271 / 279
页数:9
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