Ware Lorraine B, Koyama Tatsuki, Zhao Zhiguo, Janz David R, Wickersham Nancy, Bernard Gordon R, May Addison K, Calfee Carolyn S, Matthay Michael A
Crit Care. 2013 Oct 24;17(5):R253. doi: 10.1186/cc13080.
Despite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.
This was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.
Using the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.
Abnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.
尽管近期有所修订，但急性呼吸窘迫综合征（ARDS）的临床定义仍不具有特异性，导致诊断不足和治疗不足。本研究旨在检验这样一个假设，即生物标志物组合对于因严重脓毒症而有发生ARDS风险的患者的ARDS临床诊断的生物学确认有用。
这是一项回顾性病例对照研究，将100例患有严重脓毒症且无ARDS证据的患者与100例患有严重脓毒症且在其入住ICU的前四天中至少有两天有ARDS证据的患者进行比较。在入住ICU第二天上午采集的血浆中检测了一个包含炎症、成纤维细胞活化、蛋白水解损伤、内皮损伤和肺上皮损伤的11种生物标志物的组合。采用基于1000次自抽样数据的向后消除模型构建策略，选择表现最佳的生物标志物，以便在用于ARDS诊断的逻辑回归模型中进一步考虑。
使用表现最佳的五种生物标志物（表面活性蛋白-D（SP-D）、晚期糖基化终产物受体（RAGE）、白细胞介素-8（IL-8）、克拉拉细胞分泌蛋白（CC-16）和白细胞介素-6（IL-6）），诊断ARDS的受试者操作特征曲线（AUC）下面积为0.75（95%CI：0.7至0.84）。对于定义为入住ICU的前四天全部四天均存在ARDS的严重ARDS诊断，AUC提高到0.82（95%CI：0.77至0.90）。
包括三种由肺上皮产生的生物标志物（SP-D、RAGE、CC-16）在内的五种血浆生物标志物水平异常，对严重脓毒症患者的ARDS诊断具有出色的鉴别能力。血浆生物标志物水平的改变可能有助于对脓毒症患者的ARDS诊断进行生物学确认，也可能有助于选择患者参加旨在减少肺上皮损伤的临床试验。
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