BACKGROUND Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is devastating with no established treatment. This phenomenon involves disordered coagulation and excessive inflammatory reactions. As recombinant human soluble thrombomodulin (rhsTM) possesses anti-coagulative and anti-inflammatory properties, the medicine is expected to improve the prognosis of the disease. The aim of this study was to summarize current evidence regarding benefits and harms of rhsTM treatment for AE of IPF. METHOD Patients with AE of IPF were eligible for the review and all of the other types of interstitial pneumonias were excluded. The effect of rhsTM treatment on the outcomes such as all-cause mortality was estimated in comparison to conventional therapy. Primary studies of any design aside from a case report were reviewed. Electronic databases such as Medline and EMBASE were searched from 2002 through August 14, 2019. Two reviewers independently selected eligible reports and extracted relevant data. A risk of bias of individual studies was assessed similarly. Meta-analysis was conducted for univariate results if at least three studies were available for the same outcome. RESULT Out of a total of 390 records identified, eight studies were first deemed eligible and four of them were finally focused for the review. Only one study was a prospective trial and a historical control was employed in all studies. An overall risk of bias was rated as serious in three out of four studies. A total of 169 subjects were included. Two out of three studies that reported 3-month all-cause mortality by univariate analysis demonstrated beneficial effects of rhsTM treatment and a pooled analysis demonstrated that rhsTM treatment improved 3-month all-cause mortality with a risk ratio of 0.50 (95% confidence interval (CI): 0.35-0.72). All two studies reporting multivariate results demonstrated that rhsTM treatment improved 3-month all-cause mortality with odds ratios of 0.21 (95% CI: 0.05-0.91) and 0.25 (95% CI: 0.09-0.68), respectively. There were no serious adverse events. CONCLUSION The rhsTM treatment was demonstrated to improve 3-month all-cause mortality of AE of IPF with no serious adverse events. However, these findings should be interpreted with caution due to a small number of studies and serious risk of bias.

中文翻译：

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重组人可溶性血栓调节蛋白（rhsTM）治疗特发性肺纤维化急性加重的疗效：系统评价和荟萃分析。

背景技术特发性肺纤维化（IPF）的急性加重（AE）是毁灭性的，没有确定的治疗方法。这种现象涉及凝血异常和过度的炎症反应。由于重组人可溶性血栓调节蛋白（rhsTM）具有抗凝和抗炎特性，因此该药物有望改善疾病的预后。这项研究的目的是总结有关rhsTM治疗IPF AE利弊的最新证据。方法符合IPF AE要求的患者有资格接受复查，所有其他类型的间质性肺炎均排除在外。与传统疗法相比，估计了rhsTM治疗对诸如全因死亡率之类的结果的影响。审查了除病例报告外任何设计的基础研究。从2002年到2019年8月14日，搜索了Medline和EMBASE等电子数据库。两名审稿人独立选择了合格的报告并提取了相关数据。类似地评估了个别研究的偏倚风险。如果至少三项研究可获得相同结果，则对单因素结果进行荟萃分析。结果在确定的390条记录中，有8项研究首先被认为是合格的，其中4项最终成为审查的重点。仅一项研究为前瞻性试验，所有研究均采用历史对照。在四项研究中，有三项的总体偏倚风险为严重。总共包括169名受试者。三分之二的研究通过单因素分析报告了3个月的全因死亡率，证明了rhsTM治疗的有益作用，汇总分析表明rhsTM的治疗可改善3个月的全因死亡率，风险比为0.50（95％置信区间（CI）：0.35-0.72）。两项报告多变量结果的研究均表明，rhsTM治疗可改善3个月全因死亡率，优势比分别为0.21（95％CI：0.05-0.91）和0.25（95％CI：0.09-0.68）。没有严重的不良事件。结论rhsTM治疗可改善IPF AE的3个月全因死亡率，无严重不良事件。但是，由于研究数量少和存在严重偏见的风险，因此应谨慎解释这些发现。