{"title":"中性粒细胞弹性酶抑制剂（西维司他）治疗COVID-19急性呼吸窘迫综合征：一项多中心回顾性队列研究","authors":"Yuting Li, Jianjun Zhao, Jiahui Wei, Yanhong Zhang, Haitao Zhang, Ying Li, Ting Liao, Yang Hu, Bo Yuan, Xinmei Zhang, Wanyan Liu, Changgang Liu, Qingsong Cui, Shunzi Wu, Hongmei Jiang, Wenge Liu, Weiheng Liu, Hongguang Xu, Gang Li, Yuyan Cai, Liting Chen, Bingwei Chen, Dong Zhang","doi":"10.1186/s12931-025-03100-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Recent studies suggest that neutrophil elastase inhibitor (Sivelestat) may improve pulmonary function and reduce mortality in patients with acute respiratory distress syndrome. We examined the association between receipt of sivelestat and improvement in oxygenation among patients with acute respiratory distress syndrome (ARDS) induced by COVID-19.</p><p><strong>Methods: </strong>A large multicentre cohort study of patients with ARDS induced by COVID-19 who had been admitted to intensive care units (ICUs). We used propensity score matching to compare the outcomes of patients treated with sivelestat to those who were not. The differences in continuous outcomes were assessed with the Wilcoxon signed-rank test. Kaplan-Meier method was used to show the 28-day survival curves in the matched cohorts. A log-rank P-test stratified on the matched pairs was used to test the equality of the estimated survival curves. A Cox proportional hazards model that incorporated a robust sandwich-type variance estimator to account for the matched nature of the data was used to estimate hazard ratios (HR). All statistical analyses were performed with SPSS 26.0 and R 4.2.3. A two-sided p-value of < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>A total of 387 patients met inclusion criteria, including 259 patients (66.9%) who were treated with sivelestat. In 158 patients matched on the propensity for treatment, receipt of sivelestat was associated with improved oxygenation, decreased Murray lung injury score, increased non-mechanical ventilation time within 28 days, increased alive and ICU-free days within 28 days (HR, 1.85; 95% CI 1.29 to 2.64; log-rank p < 0.001), shortened ICU stay and ultimately improved survival (HR, 2.78; 95% CI 1.32 to 5.88; log-rank p = 0.0074).</p><p><strong>Conclusions: </strong>Among patients with ARDS induce by COVID-19, sivelestat administration is associated with improved clinical outcomes.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"26 1","pages":"28"},"PeriodicalIF":5.8000,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743030/pdf/","citationCount":"0","resultStr":"{\"title\":\"Neutrophil elastase inhibitor (Sivelestat) in the treatment of acute respiratory distress syndrome induced by COVID-19: a multicenter retrospective cohort study.\",\"authors\":\"Yuting Li, Jianjun Zhao, Jiahui Wei, Yanhong Zhang, Haitao Zhang, Ying Li, Ting Liao, Yang Hu, Bo Yuan, Xinmei Zhang, Wanyan Liu, Changgang Liu, Qingsong Cui, Shunzi Wu, Hongmei Jiang, Wenge Liu, Weiheng Liu, Hongguang Xu, Gang Li, Yuyan Cai, Liting Chen, Bingwei Chen, Dong Zhang\",\"doi\":\"10.1186/s12931-025-03100-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Recent studies suggest that neutrophil elastase inhibitor (Sivelestat) may improve pulmonary function and reduce mortality in patients with acute respiratory distress syndrome. We examined the association between receipt of sivelestat and improvement in oxygenation among patients with acute respiratory distress syndrome (ARDS) induced by COVID-19.</p><p><strong>Methods: </strong>A large multicentre cohort study of patients with ARDS induced by COVID-19 who had been admitted to intensive care units (ICUs). We used propensity score matching to compare the outcomes of patients treated with sivelestat to those who were not. The differences in continuous outcomes were assessed with the Wilcoxon signed-rank test. Kaplan-Meier method was used to show the 28-day survival curves in the matched cohorts. A log-rank P-test stratified on the matched pairs was used to test the equality of the estimated survival curves. A Cox proportional hazards model that incorporated a robust sandwich-type variance estimator to account for the matched nature of the data was used to estimate hazard ratios (HR). All statistical analyses were performed with SPSS 26.0 and R 4.2.3. A two-sided p-value of < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>A total of 387 patients met inclusion criteria, including 259 patients (66.9%) who were treated with sivelestat. 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引用次数: 0
摘要
背景：最近的研究表明，中性粒细胞弹性酶抑制剂（西维司他）可以改善急性呼吸窘迫综合征患者的肺功能，降低死亡率。我们研究了西司他与COVID-19引起的急性呼吸窘迫综合征（ARDS）患者氧合改善之间的关系。方法：对重症监护病房（icu）收治的COVID-19急性呼吸窘迫综合征（ARDS）患者进行大型多中心队列研究。我们使用倾向评分匹配来比较接受西司他治疗的患者和未接受西司他治疗的患者的结果。用Wilcoxon符号秩检验评估连续结果的差异。Kaplan-Meier法显示匹配队列的28天生存曲线。采用配对对分层的对数秩p检验来检验估计生存曲线的平稳性。Cox比例风险模型结合了一个稳健的三明治型方差估计器来考虑数据的匹配性，用于估计风险比（HR）。所有统计分析均采用SPSS 26.0和R 4.2.3进行。结果的双侧p值：共有387例患者符合纳入标准，其中接受西司他治疗的患者259例（66.9%）。在158例治疗倾向匹配的患者中，接受西司他可改善氧合，降低Murray肺损伤评分，增加28天内的非机械通气时间，增加28天内的存活天数和无icu天数(HR, 1.85；95% CI 1.29 - 2.64；结论：在COVID-19诱导的ARDS患者中，西司他可改善临床预后。
Neutrophil elastase inhibitor (Sivelestat) in the treatment of acute respiratory distress syndrome induced by COVID-19: a multicenter retrospective cohort study.
Background: Recent studies suggest that neutrophil elastase inhibitor (Sivelestat) may improve pulmonary function and reduce mortality in patients with acute respiratory distress syndrome. We examined the association between receipt of sivelestat and improvement in oxygenation among patients with acute respiratory distress syndrome (ARDS) induced by COVID-19.
Methods: A large multicentre cohort study of patients with ARDS induced by COVID-19 who had been admitted to intensive care units (ICUs). We used propensity score matching to compare the outcomes of patients treated with sivelestat to those who were not. The differences in continuous outcomes were assessed with the Wilcoxon signed-rank test. Kaplan-Meier method was used to show the 28-day survival curves in the matched cohorts. A log-rank P-test stratified on the matched pairs was used to test the equality of the estimated survival curves. A Cox proportional hazards model that incorporated a robust sandwich-type variance estimator to account for the matched nature of the data was used to estimate hazard ratios (HR). All statistical analyses were performed with SPSS 26.0 and R 4.2.3. A two-sided p-value of < 0.05 was considered statistically significant.
Results: A total of 387 patients met inclusion criteria, including 259 patients (66.9%) who were treated with sivelestat. In 158 patients matched on the propensity for treatment, receipt of sivelestat was associated with improved oxygenation, decreased Murray lung injury score, increased non-mechanical ventilation time within 28 days, increased alive and ICU-free days within 28 days (HR, 1.85; 95% CI 1.29 to 2.64; log-rank p < 0.001), shortened ICU stay and ultimately improved survival (HR, 2.78; 95% CI 1.32 to 5.88; log-rank p = 0.0074).
Conclusions: Among patients with ARDS induce by COVID-19, sivelestat administration is associated with improved clinical outcomes.
期刊介绍：
Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases.
As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion.
Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.
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