Diagnostic and prognostic value of Ang-2 in ARDS: a systemic review and meta-analysis

To investigate the diagnostic and prognostic value of angiopoietin-2 (Ang-2) for acute respiratory distress syndrome (ARDS). Seven databases (4 English and 3 Chinese databases) were searched, the quality was evaluated by QUADAS-2 and GRADE profile. The bivariate model was employed to combine area under the curve (AUC), pooled sensitivity (pSEN) and pooled specificity (pSPE), the Fagan’s nomogram was employed for evaluating clinical utility. This study was registered in PROSPERO (NO.CRD42022371488). 18 eligible studies comprising 27 datasets (12 diagnostic and 15 prognostic datasets) were included for meta-analysis. For diagnostic analysis, Ang-2 yielded an AUC of 0.82, with a pSEN of 0.78 and a pSPE of 0.74; in clinical utility analysis, a pretest probability of 50% regulated the post probability positive (PPP) of 75% and the post probability negative (PPN) of 23%. In prognostic analysis, Ang-2 yielded an AUC of 0.83, with a pSEN of 0.69, a pSPE of 0.81, and good clinical utility (a pretest probability of 50% regulated the PPP of 79% and the PPN of 28%). Heterogeneity existed in both diagnostic and prognostic analysis. Ang-2 demonstrates promising diagnostic and prognostic capabilities as a noninvasive circulating biomarker for ARDS, especially in the Chinese population. It is advisable to dynamically monitor Ang-2 in critically ill patients both suspected and with confirmed ARDS.

本研究旨在探讨血管生成素-2（angiopoietin-2, Ang-2）对急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS）的诊断与预后价值。本研究检索了7个数据库（含4个英文数据库与3个中文数据库），采用QUADAS-2量表与GRADE证据分级工具对研究质量进行评估。采用双变量模型合并曲线下面积（area under the curve, AUC）、合并灵敏度（pooled sensitivity, pSEN）与合并特异度（pooled specificity, pSPE），并使用Fagan列线图（Fagan’s nomogram）评估临床应用价值。本研究已在PROSPERO国际前瞻性注册系统注册（注册号：CRD42022371488）。最终纳入18项符合纳入标准的研究，共计27个数据集（其中12个为诊断数据集、15个为预后数据集）用于荟萃分析。诊断分析结果显示，Ang-2的曲线下面积为0.82，合并灵敏度为0.78，合并特异度为0.74；临床应用价值分析结果显示，当检验前概率为50%时，阳性后概率（post probability positive, PPP）可升至75%，阴性后概率（post probability negative, PPN）可降至23%。预后分析结果显示，Ang-2的曲线下面积为0.83，合并灵敏度为0.69，合并特异度为0.81，且具备良好的临床应用价值：当检验前概率为50%时，阳性后概率可升至79%，阴性后概率可降至28%。诊断与预后分析均存在异质性。作为一种无创循环生物标志物，Ang-2对ARDS具备良好的诊断与预后价值，尤其在中国人群中表现突出。建议对疑似或确诊ARDS的重症患者动态监测Ang-2水平。