目的：探讨乌司他丁对预防急性呼吸窘迫综合征（acute respiratory distress syndrome，ARDS）的作用。方法： 采用前瞻性随机对照试验，选择2012年1月至2014年12月北京大学第三医院危重医学科、沧州市人民医院、中国中医科学院西苑医院和北京中日友好医院重症医学科的185例患者，随机分为干预组（n=77）和对照组（n=108）。两组患者均接受常规治疗，干预组患者入重症监护病房（intensive care unit，ICU）后在常规治疗基础上每天加用乌司他丁60万单位，静脉输注，连用5 d；对照组静脉输注等体积生理盐水，连续5 d。于干预的第1、3、7天分别检测静脉血中性粒细胞弹性蛋白酶（human neutrophil elastase，HNE）和中性粒细胞弹性蛋白酶抑制剂（peptidase inhibitor 3，PI3）的水平，计算HNE/PI3比值，监测患者急性生理学及慢性健康状况评分（acute physiology and chronic health evaluation scoring Ⅱ，APACHE Ⅱ）、体温、呼吸频率、心率、平均动脉压、白细胞计数、氧合指数（PaO2/FiO2），并记录两组患者ARDS发生率、机械通气时间、ICU治疗时间、住院时间及28 d生存率。结果： 两组患者在性别、年龄、APACHE Ⅱ评分、吸烟情况、基础疾病情况、入院诊断等方面差异无统计学意义。两组患者的3次HNE检测值比较（第1、3、7天）差异均无统计学意义，两组患者第1天PI3检测值比较差异无统计学意义，第3天及第7天PI3的检测值比较差异均有统计学意义（P<0.01）；两组患者第1天HNE/PI3比值比较差异无统计学意义，第3天及第7天的HNE/PI3比值差异有统计学意义（P<0.05）。两组患者在第1、3、7天的体温、呼吸频率、心率、平均动脉压、白细胞计数方面的比较差异均无统计学意义；两组患者第1天的氧合指数比较差异无统计学意义，第3天及第7天的氧合指数比较差异有统计学意义（P<0.05）。干预组患者ARDS的发生率为15.58%，明显低于对照组的33.33%，差异有统计学意义（P<0.05）。在两组进展为ARDS的患者中，均以脓毒症、腹部术后及胰腺炎患者为主。干预组患者的机械通气时间、ICU治疗时间短于对照组，差异有统计学意义（P<0.05）。两组患者的住院时间差异无统计学意义，干预组患者的28 d生存率高于对照组，但两组差异无统计学意义。结论： 通过增加外源性HNE拮抗剂乌司他丁，可以恢复HNE与其拮抗剂的平衡，对抗HNE对肺组织的破坏作用，降低ARDS的发病率。

Objective：To explore the effect of ulinastatin on prevention of acute respiratory distress syndrome (ARDS). Methods: A prospective multicentral cohort study was conducted. The patients from three intensive care units (ICUs) of grade A tertiary hospitals in Beijing and a ICU of grade A tertiary hospitals in Cangzhou from January 2012 to December 2014, included 77 ARDS atrisk patients with ulinastatin treatment and 108 ARDS atrisk patients without ulinastatin treatment (control) were eligible. Both groups received normal treatment; additionally, the intervention group received 600 000 units of ulinastatin via intravenous infusion for 5 days. The control group received the same amount of saline via intravenous infusion for 5 days. Venous blood human neutrophil elastase (HNE) and peptidase inhibitor 3 (PI3) levels were measured on days 1, 3, and 7, respectively. Other outcomes included acute physiology and chronic health evaluation scoring Ⅱ (APACHE Ⅱ), body temperature, respiratory rate, heart rate, mean arterial pressure, white blood cell counts, PaO2/FiO2, ARDS incident, mechanical ventilation time, ICU treatment and hospitalization duration, 28 days mortality.  Results: The PI3 levels showed no statistical difference on day 1, but significant differences on day 3 and day 7 between the two groups (P<0.01). HNE/PI3 ratio showed no statistical difference on day 1, but significant differences on day 3 and day 7 (P<0.05). PaO2/FiO2 was significantly higher in ulinastatin group on day 3 and day 7 (P<0.05). The incident rate for ulinastatin group was 15.58%, lower than that for the control group (33.33%), and the difference was statistically significant (P<0.05). The mechanical ventilation time and ICU treatment time in ulinastatin group was shorter than that in the control group, and the difference was statistically significant (P<0.05). There were no significant effects in other factors. Conclusion: Increased dose of ulinastatin can recover the balance of HNE and its antagonist, lower the HNE’s damage to lungs, and further reduce the ARDS incident rate.