81. Biomarkers of Lung Contusion With/Without Superimposed Gastric Aspiration in Rats

Abstract

Introduction: Lung contusion (LC) is an independent risk factor for ALI/ARDS. Previous work in our laboratory suggests that lung injury in LC is self-limiting and it is the additional insult such as gastric aspiration that may be responsible for progression of LC into ALI/ARDS. Considering that gastric aspiration, a common injury seen in victims of blunt trauma, is usually unwitnessed, it is important to analyze the biomarker profiles of these two insults individually and in combination. Materials and Methods: Rats received LC, CASP (combined acid and small particles), LC+CASP, uninjured controls (n=9-12) and were analyzed at 5 and 24hr following the insults. A qualitative, quantitative cellular analysis of the BAL (broncho-alveolar Lavage) along with levels of albumin, IL-1β, TNFα, IL-6, IL-10, CINC-1, MIP-2, MCP-1 in the BAL were determined by ELISA. Additionally, total lung MPO levels were also determined. Statistical Methods: JMP statistical software was used to perform hierarchial clusters of the biomarker profiles of the individual insults. The prediction of injury type was carried out using an approach recently defined by Hutson to extend standard ROC methodology. In brief, lung injury type was modeled as a two-by-two outcome with injury group. Analyses tested the predictive accuracy of models incorporating a maximum of two inflammatory mediators at a fixed time of injury and for a fixed type of aspiration. Results: A hierachial cluster analyses at 5hr (figure 1) and 24hr suggested that LC, CASP, LC+CASP, control groups had very different biomarker profiles. Additionally using the prediction model methodology, the cytokines with the greatest predictive utility in rats at 5 hr (Table 1) varied with the type of insult, with IL-10 and BAL macrophages found to be best predictor for LC, and total lung MPO best for CASP. Only 1/30 rats were misclassified for the type of injury based on modeling with cytokine levels at 5 hr. At 24 hr based on just 2 mediators IL-10 and BAL PMNs, all but 1/37 rats were correctly classified (Table 1). Only one rat in the LC group was misclassified as LC+CASP. The predictive modeling worked perfectly well with CASP and LC+CASP suggesting distinct inflammatory signature profiles for differing lung insults. Conclusions: Biomarker profiles in inflammatory lung injuries may play a key role in early diagnosis of these clinically relevant problems. Tabled 1