Plasma Angiopoietin-2 Predicts the Onset of Acute Lung Injury in Critically III Patients
Plasma Angiopoietin-2 Predicts the Onset of Acute Lung Injury in Critically III Patients
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DOI：
10.1164/rccm.201208-1460oc
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发表时间：
2013-04-01
影响因子：
24.7
通讯作者：
Calfee, Carolyn S.
中科院分区：
文献类型：
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作者：
Agrawal, Ashish;Matthay, Michael A.;Calfee, Carolyn S.
理论基础：目前对急性肺损伤(ALI)的临床预测评分具有有限的阳性预测价值。目前尚无研究评估血浆生物标志物在危重病患者中的预测作用或作为临床预测评分的辅助指标。目的：确定血浆血管生成素-2(Ang-2)、血管性血友病因子(VWF)、白介素8(IL-8)和/或晚期糖基化终产物受体(SARAGE)是否能预测危重病患者的ALI。排除基线或随后6小时内发生ALI的患者，其余患者进行ALI随访。测量和主要结果：19例患者在抽样后至少6小时发生ALI。血浆Ang-2和IL-8水平升高与ALI的发生发展密切相关(P分别为0.0008和0.004)。血管紧张素转换酶-2和随后的ALI发展之间的关联对于脓毒症和血管加压药的使用的调整是强有力的。Ang-2和肺损伤预测评分分别独立区分ALI患者和未发生ALI患者(受试者工作特征曲线下面积，分别为0.74)，两者联合使用可将曲线下面积提高到0.84(vs.0.74，P=0.05)。相反，血浆sRAGE和vWF水平不能预测ALL。结论：Ang-2等血浆生物标志物可以提高临床预测分数，识别ALI的高危患者。此外，Ang-2的早期升高强调了内皮损伤在ALI早期发病机制中的重要性。
Rationale: Current clinical prediction scores for acute lung injury (ALI) have limited positive predictive value. No studies have evaluated predictive plasma biomarkers in a broad population of critically ill patients or as an adjunct to clinical prediction scores.Objectives: To determine whether plasma angiopoietin-2 (Ang-2), von Willebrand factor (vWF), interleukin-8 (IL-8), and/or receptor for advanced glycation end products (sRAGE) predict ALI in critically ill patients.Methods: Plasma samples were drawn from critically ill patients (n = 230) identified in the emergency department. Patients who had ALI at baseline or in the subsequent 6 hours were excluded, and the remaining patients were followed for development of ALI.Measurements and Main Results: Nineteen patients developed ALI at least 6 hours after the sample draw. Higher levels of Ang-2 and IL-8 were significantly associated with increased development of ALI (P = 0.0008, 0.004, respectively). The association between Ang-2 and subsequent development of ALI was robust to adjustment for sepsis and vasopressor use. Ang-2 and the Lung Injury Prediction Score each independently discriminated well between those, who developed ALI and those who did not (area under the receiver operating characteristic curve, 0.74 for each), and using the two together improved the area under the curve to 0.84 (vs. 0.74, P = 0.05). In contrast, plasma levels-of sRAGE and vWF were not predictive of All.Conclusions: Plasma biomarkers such as Ang-2 can improve clinical prediction scores and identify patients at high risk for ALI. In addition, the early rise of Ang-2 emphasizes the importance of endothelial injury in the early pathogenesis of ALI.