Raghavendran Krishnan, Davidson Bruce A, Hutson Alan D, Helinski Jadwiga D, Nodzo Scott R, Notter Robert H, Knight Paul R
Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
J Trauma. 2009 Dec;67(6):1182-90. doi: 10.1097/TA.0b013e318187a2bf.
This study uses statistical predictive modeling and hierarchical cluster analyses to examine inflammatory mediators and cells in bronchoalveolar lavage (BAL) as putative biomarkers in rats with blunt trauma lung contusion (LC), gastric aspiration (combined acid and small gastric food particles, CASP), or a combination of the two.
Specific parameters assessed in the innate pulmonary inflammatory response were leukocytes, macrophages, and polymorphonuclear neutrophils (PMNs) in BAL; whole lung myeloperoxidase activity; and a series of cytokines or chemokines present in BAL at 5 or 24 hours after injury: tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, interferon-gamma, IL-10, macrophage inflammatory protein-2, cytokine-induced neutrophil chemoattractant-1, and monocyte chemoattractant protein-1.
Rats with LC, CASP, LC + CASP all had severe lung injury compared with uninjured controls based on decreased arterial oxygenation or increased BAL albumin at 5 or 24 hours postinsult. However, the injury groups had distinct overall patterns of inflammation that allowed them to be discriminated accurately by hierarchical cluster analysis (29 of 30 and 35 of 37 rats were correctly classified in hierarchical clusters at 5 and 24 hours, respectively). Moreover, predictive analyses based on an extension of standard receiver-operator characteristic methodology discriminated individual animals and groups with similar high accuracy based on a maximum of two inflammatory parameters per group (29 of 30 and 36 of 37 rats were correctly classified at 5 hours and 24 hours, respectively).
These results support the possibility that inflammatory biomarker profiles could be developed in the future to improve the diagnosis and management of trauma patients with unwitnessed (occult) gastric aspiration who have an increased risk of clinical acute lung injury or the acute respiratory distress syndrome.
本研究采用统计预测模型和层次聚类分析，以检查支气管肺泡灌洗（BAL）中的炎症介质和细胞，作为钝性创伤性肺挫伤（LC）、胃内容物误吸（胃酸和小颗粒胃内容物混合物，CASP）或两者兼具的大鼠的潜在生物标志物。
评估先天性肺部炎症反应的具体参数包括BAL中的白细胞、巨噬细胞和多形核中性粒细胞（PMN）；全肺髓过氧化物酶活性；以及损伤后5或24小时BAL中存在的一系列细胞因子或趋化因子：肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6、干扰素-γ、IL-10、巨噬细胞炎性蛋白-2、细胞因子诱导的中性粒细胞趋化因子-1和单核细胞趋化蛋白-1。
与未受伤的对照组相比，LC、CASP、LC + CASP大鼠在损伤后5或24小时均出现严重肺损伤，表现为动脉氧合降低或BAL白蛋白增加。然而，损伤组具有独特的整体炎症模式，通过层次聚类分析能够准确区分（分别在5和24小时时，30只大鼠中有29只、37只大鼠中有35只被正确分类到层次聚类中）。此外，基于标准受试者工作特征方法扩展的预测分析，每组最多根据两个炎症参数就能以相似的高精度区分个体动物和组（分别在5小时和24小时时，30只大鼠中有29只、37只大鼠中有36只被正确分类）。
这些结果支持未来有可能开发炎症生物标志物谱，以改善对临床急性肺损伤或急性呼吸窘迫综合征风险增加的无目击者（隐匿性）胃内容物误吸创伤患者的诊断和管理。
