肺泡液可溶性髓系细胞触发受体-1水平对呼吸机相关性肺炎早期诊断价值的Meta分析

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目的:血清可溶性髓系细胞触发受体-1(sTREM-1)是一种用于区分细菌感染与非细菌感染的生物标志物,但肺泡液中sTREM-1水平在肺部感染中的诊断价值仍不明确。通过对相关文献进行系统评价,探讨肺泡液中sTREM-1水平在呼吸机相关性肺炎(VAP)早期诊断中的价值。方法:检索中国知网(CNKI)、万方数据库、维普数据库(VIP)、美国国立医学图书馆数据库(PubMed/Medline)和荷兰医学文摘(Embase)等数据库,截至2019年6月30日发布的有关sTREM-1诊断VAP的文献。采用Cochrane协作网提供的QUADAS-2量表进行文献质量评价。应用RevMan 5.3和Stata 13.0软件完成Meta分析,比较VAP与非VAP患者的sTREM-1水平,再通过诊断试验Meta分析评价sTREM-1对VAP的早期诊断价值,并进行异质性、敏感性及发表偏倚分析。结果:最终共有24篇文献入选,QUADAS-2量表评价提示入选文献均具有较低的偏倚和较高的临床适应性。①在对肺泡液中sTREM-1水平进行Meta分析时共入选20篇文献,存在高度异质性(n I2=94.4%,n P=0.000),故采用随机效应模型分析,结果显示,与非VAP组相比,VAP组患者肺泡液中sTREM-1水平明显升高,差异有统计学意义〔标准化均数差(n SMD)为1.47,95%可信区间(95%n CI)为1.00~1.95,n Z=6.14,n P=0.000〕。通过亚组分析和回归分析未发现异质性来源;敏感性分析提示Meta分析的结果尚稳健可信;Begg漏斗图分析显示纳入文献不存在明显发表偏倚(n Z=1.46,n P=0.143)。②在进行诊断试验的Meta分析时共入选18篇文献,Deek漏斗图显示纳入文献存在发表偏倚(n P=0.012)。合并的敏感度为0.87(95%n CI为0.81~0.91),特异度为0.80(95%n CI为0.73~0.86),诊断优势比(n DOR)为26(95%n CI为13~50);对肺泡液3种不同的标本来源(支气管肺泡灌洗液、气管内抽吸液和呼出气冷凝液)进行亚组分析显示,不同肺泡液中sTREM-1水平对VAP均有一定早期诊断价值。合并n DOR的n I2=35.4%,敏感度的n I2=79.46%,特异度的n I2=77.61%,提示入选文献存在异质性;亚组分析显示,异质性与国籍、课题设计、样本来源、样本量和诊断“金标准”有关,但与年龄无关。肺泡液中sTREM-1水平诊断VAP的综合受试者工作特征曲线下面积(AUC)为0.90(95%n CI为0.87~0.92)。n 结论:肺泡液中sTREM-1水平可用于VAP的早期诊断,有一定敏感度和特异度,但影响因素较多,联合其他生物标志物可能更有诊断价值。“,”Objective:Serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a useful biomarker of bacterial infection. However, the diagnostic value of sTREM-1 of alveolar fluid in pulmonary infection is still unclear. This article aimed to explore the value of sTREM-1 of alveolar fluid in the early diagnosis of ventilator-associated pneumonia (VAP) by systematic review of relevant literatures.Methods:CNKI, Wanfang, VIP, PubMed/Medline and Embase databases were retrieved. Articles on diagnosis of VAP by sTREM-1 before June 30, 2019 were collected. QUADAS-2 scale provided by Cochrane Collaboration Network was used to evaluate the quality of diagnostic experiments. RevMan 5.3 and Stata 13.0 software were used to complete Meta-analysis. The levels of sTREM-1 between VAP and non-VAP patients were analyzed by Meta-analysis, and then diagnostic test Meta-analysis was conducted. Heterogeneity, sensitivity and publication bias were analyzed.Results:A total of 24 articles were enrolled. QUADAS-2 scale indicated that the selected literature had low bias and high clinical adaptability. ① In Meta-analysis of sTREM-1 level in alveolar fluid, 20 articles were selected and found to have high heterogeneity (n I2 = 94.4%, n P = 0.000). The random effects models were used for Meta-analysis. It was indicated that the sTREM-1 level in alveolar fluid of VAP group was significantly higher than that of non-VAP group with significant difference [standardized mean difference (n SMD) was 1.47, 95% confidence interval (95%n CI) was 1.00-1.95, n Z = 6.14, n P = 0.000]. By subgroup analysis and Meta-regression analysis, no source of heterogeneity was found. Sensitivity analysis suggested that the results of this Meta-analysis were robust and credible, and Begg funnel plot analysis showed that there was no significant publication bias (n Z = 1.46, n P = 0.143). ② A total of 18 articles were included in the Meta-analysis of diagnostic experiments. Deek funnel plot showed publication bias (n P = 0.012). The combined sensitivity was 0.87 (95%n CI was 0.81-0.91), specificity was 0.80 (95%n CI was 0.73-0.86), and diagnostic odds ratio (n DOR) was 26 (95%n CI was 13-50). Subgroup analysis of three different sources of alveolar fluid (bronchoalveolar lavage fluid, endotracheal aspiration fluid and exhaled ventilator condensate) showed that STREM-1 had a certain value in early diagnosis of VAP. The n I2 of combined n DOR was 35.4%, and n I2 of sensitivity was 79.46%, n I2 of specificity was 77.61%, suggesting heterogeneity in the selected literature. Subgroup analysis found that nationality, subject design, sample source, sample size and diagnostic “gold criteria” were related to heterogeneity, but not age. The area under synthetic receiver operating characteristic (SROC) curve (AUC) was 0.90 (95% n CI was 0.87-0.92).n Conclusions:The detection of sTREM-1 level in alveolar fluid can be used for the early diagnosis of VAP with high sensitivity and specificity. If combined with other biomarkers, it may have more diagnostic value.
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