Inoue Yoshiaki, Tanaka Hiroshi, Ogura Hiroshi, Ukai Isao, Fujita Kieko, Hosotsubo Hideo, Shimazu Takeshi, Sugimoto Hisashi
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
J Trauma. 2006 May;60(5):936-43; discussion 943. doi: 10.1097/01.ta.0000217271.25809.a0.
The objective of this study was to evaluate whether the neutrophil elastase (NE) inhibitor, sivelestat, improves leukocyte deformability and pulmonary function in patients with acute lung injury (ALI).
Twenty-four patients with systemic inflammatory response syndrome (SIRS) were divided into two groups: those with ALI (ALI group, n = 14), and those without ALI (non-ALI group, n = 10). Within 72 hours after the diagnosis, we measured the total leukocyte count (TLC), C-reactive protein (CRP) level, NE concentration, APACHE II score, Goris multiple organ failure (MOF) index, respiratory index (RI), lung injury score (LIS), and oxygenation index (P/F ratio). Leukocyte deformability was examined with a microchannel array etched on a single-crystal silicon tip that simulates the microvasculature. The number of obstructed microchannels (NOM) because of stiffened neutrophils and transit time (TT), defined as the time needed for 100 microL of whole blood to pass through the microchannels, were determined. We then administered sivelestat (4.8 mg/kg/d) to nine ALI patients (sivelestat group) for 5 days and compared with seven ALI patients treated previously without sivelestat (conventional group). The factors described above were measured before and 5 days after treatment.
There were no significant differences in age, TLC, CRP, APACHE II score, and MOF index between ALI and non-ALI group. RI and LIS were higher and the P/F ratio was significantly lower in the ALI group than in the non-ALI group. NE concentration, NOM, and TT were significantly higher in the ALI group than in the non-ALI group (p < 0.05). After 5 days of treatment with sivelestat, the APACHE II score, MOF index, RI, LIS, NE concentration, TT, and NOM were lower and the P/F ratio was significantly higher than baseline values and those in the conventional group (p < 0.05).
NE concentration and neutrophil rigidity are significantly increased in SIRS patients with ALI. Sivelestat appears to reduce NE concentration and neutrophil stiffness and improve pulmonary oxygenation in patients with ALI.
本研究的目的是评估中性粒细胞弹性蛋白酶（NE）抑制剂西维来司他是否能改善急性肺损伤（ALI）患者的白细胞变形能力和肺功能。
24例全身炎症反应综合征（SIRS）患者被分为两组：ALI患者（ALI组，n = 14）和非ALI患者（非ALI组，n = 10）。在诊断后72小时内，我们测量了白细胞总数（TLC）、C反应蛋白（CRP）水平、NE浓度、急性生理与慢性健康状况评分系统II（APACHE II）评分、戈里斯多器官功能衰竭（MOF）指数、呼吸指数（RI）、肺损伤评分（LIS）和氧合指数（P/F比值）。使用刻蚀在模拟微血管的单晶硅尖端上的微通道阵列检测白细胞变形能力。确定由于中性粒细胞变硬导致的微通道阻塞数量（NOM）和通过时间（TT），通过时间定义为100微升全血通过微通道所需的时间。然后，我们对9例ALI患者（西维来司他组）给予西维来司他（4.8毫克/千克/天），持续5天，并与7例先前未接受西维来司他治疗的ALI患者（常规组）进行比较。在治疗前和治疗5天后测量上述因素。
ALI组和非ALI组在年龄、TLC、CRP、APACHE II评分和MOF指数方面无显著差异。ALI组的RI和LIS高于非ALI组，而P/F比值显著低于非ALI组。ALI组的NE浓度、NOM和TT显著高于非ALI组（p < 0.05）。在用西维来司他治疗5天后，APACHE II评分、MOF指数、RI、LIS、NE浓度、TT和NOM均降低，P/F比值显著高于基线值和常规组（p < 0.05）。
ALI的SIRS患者中NE浓度和中性粒细胞硬度显著增加。西维来司他似乎能降低ALI患者的NE浓度和中性粒细胞硬度，并改善肺氧合。
