Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, CA 94143-0111, USA.
Crit Care Med. 2011 Apr;39(4):711-7. doi: 10.1097/CCM.0b013e318207ec3c.
Multiple single biomarkers have been associated with poor outcomes in acute lung injury; however, no single biomarker has sufficient discriminating power to clearly indicate prognosis. Using both derivation and replication cohorts, we tested novel risk reclassification methods to determine whether measurement of multiple plasma biomarkers at the time of acute lung injury diagnosis would improve mortality prediction in acute lung injury.
Analysis of plasma biomarker levels and prospectively collected clinical data from patients enrolled in two randomized controlled trials of ventilator therapy for acute lung injury.
Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network.
Subjects enrolled in a trial of lower tidal volume ventilation (derivation cohort) and subjects enrolled in a trial of higher vs. lower positive end-expiratory pressure (replication cohort).
None.
The plasma biomarkers were intercellular adhesion molecule-1, von Willebrand factor, interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D. In the derivation cohort (n = 547), adding data on these biomarkers to clinical predictors (Acute Physiology and Chronic Health Evaluation III score) at the time of study enrollment improved the accuracy of risk prediction, as reflected by a net reclassification improvement of 22% (95% confidence interval 13% to 32%; p < .001). In the replication cohort (n = 500), the net reclassification improvement was 17% (95% confidence interval 7% to 26%; p < .001). A reduced set of three biomarkers (interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D) had nearly equivalent prognostic value in both cohorts.
When combined with clinical data, plasma biomarkers measured at the onset of acute lung injury can improve the accuracy of risk prediction. Combining three or more biomarkers may be useful for selecting a high-risk acute lung injury population for enrollment in clinical trials of novel therapies.
多项单一生物标志物与急性肺损伤不良预后相关，但尚无单一生物标志物具有足够的区分能力来明确表明预后。通过使用推导队列和复制队列，我们测试了新的风险再分类方法，以确定在急性肺损伤诊断时测量多个血浆生物标志物是否会改善急性肺损伤的死亡率预测。
对参加 NIH 急性呼吸窘迫综合征网络呼吸机治疗急性肺损伤两项随机对照试验的患者的血浆生物标志物水平和前瞻性收集的临床数据进行分析。
参加大学医院重症监护病房。
入选低潮气量通气试验的试验对象（推导队列）和入选高 vs. 低呼气末正压通气试验的试验对象（复制队列）。
无。
血浆生物标志物为细胞间黏附分子-1、血管性血友病因子、白细胞介素-8、可溶性肿瘤坏死因子受体-1 和表面活性蛋白-D。在推导队列（n = 547）中，在研究入组时将这些生物标志物的数据添加到临床预测因子（急性生理学和慢性健康评估 III 评分）中，提高了风险预测的准确性，反映在净再分类改善 22%（95%置信区间 13%至 32%；p <.001）。在复制队列（n = 500）中，净再分类改善为 17%（95%置信区间 7%至 26%；p <.001）。两个队列中，一个由三个生物标志物（白细胞介素-8、可溶性肿瘤坏死因子受体-1 和表面活性蛋白-D）组成的简化集具有几乎相同的预后价值。
当与临床数据结合使用时，在急性肺损伤发作时测量的血浆生物标志物可以提高风险预测的准确性。结合三个或更多的生物标志物可能有助于为新型疗法的临床试验选择高危急性肺损伤人群。
