Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials
Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials
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DOI：
10.1152/ajplung.00195.2012
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发表时间：
2012-10-01
影响因子：
4.9
通讯作者：
Liu, Kathleen D.
中科院分区：
文献类型：
--
作者：
Agrawal, Ashish;Zhuo, Hanjing;Liu, Kathleen D.
Agrawal A，Zhuo H，布雷迪S，Levitt J，Steingrub J，Siegel MD，Soto G，Peterson MW，Chesnutt MS，Matthay MA，Liu KD.生物标志物在急性肺损伤和较低疾病严重程度患者中的致病性和预测价值：来自两项临床试验的结果Am J Physiol Lung Cell Mol Physiol 303：L634-L639，2012.首次发表于2012年8月3日; doi：10.1152/ajplung.00195.2012.-与急性肺损伤（ALI）发病机制相关的血浆和支气管肺泡灌洗（BAL）生物标志物与ALI患者的临床结局较差和疾病严重程度增加相关。目前尚不清楚这些生物标志物是否对排除具有高APACHE II评分的脓毒症患者的病情较轻的人群具有预测价值。我们检测了血浆和BAL生物标志物与ALI严重程度或临床相关结果的生理标志物之间的相关性，并对活化蛋白C治疗ALI的临床试验进行了二次分析。血浆纤溶酶原激活物抑制物-1（派-1）和mini-BAL蛋白均与氧合指数增加显著相关（分别为P = 0.02和0.01），而IL-6与氧合指数之间存在相关趋势（P = 0.057）。高血浆IL-6、血栓调节蛋白和mini-BAL蛋白均与较少的无呼吸机天数（VFD）显著相关（分别为P = 0.01、0.01和0.05）;没有标记物与死亡率相关，但我们假设这是由于我们队列的规模较小和死亡率较低。为了在更大的样本中证实这些相关性，我们从ARDS网络ALVEOLI研究中确定了一个具有相似基线特征的有限患者队列。我们重新测试了重要生物标志物与严重程度和临床结果标志物的相关性，并研究了IL-8作为额外的生物标志物，因为其在先前研究中具有重要的预测价值。在这个限制性队列中，IL-6与氧合指数显著相关（P = 0.02）。IL-6和IL-8均与VFD减少和28天死亡率增加相关。未来的研究应集中于检查更大数量的严重程度较低的ALI患者，以进一步检测血浆和微型BAL生物标志物对临床相关结局（包括VFD和死亡率）的相对预测价值，以及其在未来临床试验风险分层中的前瞻性效用。
Agrawal A, Zhuo H, Brady S, Levitt J, Steingrub J, Siegel MD, Soto G, Peterson MW, Chesnutt MS, Matthay MA, Liu KD. Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: results from two clinical trials. Am J Physiol Lung Cell Mol Physiol 303: L634-L639, 2012. First published August 3, 2012; doi:10.1152/ajplung.00195.2012.-Plasma and bronchoalveolar lavage (BAL) biomarkers related to the pathogenesis of acute lung injury (ALI) have previously been associated with poorer clinical outcomes and increased disease severity among patients with ALI. Whether these biomarkers have predictive value in a less severely ill population that excludes septic patients with high APACHE II scores is currently unknown. We tested the association of plasma and BAL biomarkers with physiological markers of ALI severity or clinically relevant outcomes in a secondary analysis of a clinical trial of activated protein C for the treatment of ALI. Plasma plasminogen activator inhibitor-1 (PAI-1) and mini-BAL protein were both significantly associated with increased oxygenation index (P = 0.02 and 0.01, respectively), whereas there was a trend toward an association between IL-6 and oxygenation index (P = 0.057). High plasma IL-6, thrombomodulin, and mini-BAL protein were all significantly associated with fewer ventilator-free days (VFDs) (P = 0.01, 0.01, and 0.05, respectively); no markers were associated with mortality, but we hypothesized that this was due to the small size of our cohort and the low death rate. To confirm these associations in a larger sample, we identified a restricted cohort of patients from the ARDS Network ALVEOLI study with similar baseline characteristics. We retested the associations of the significant biomarkers with markers of severity and clinical outcomes and studied IL-8 as an additional biomarker given its important predictive value in prior studies. In this restricted cohort, IL-6 was significantly associated with oxygenation index (P = 0.02). Both IL-6 and IL-8 were associated with decreased VFDs and increased 28-day mortality. Future studies should be focused on examining larger numbers of patients with less severe ALI to further test the relative predictive value of plasma and mini-BAL biomarkers for clinically relevant outcomes, including VFDs and mortality, and for their prospective utility in risk stratification for future clinical trials.