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An Evaluation of the Role of Gene Expression in the Prediction and Diagnosis of Ventilator-associated Pneumonia

Background:The SepsiChip project explored transcriptional modulation associated with ventilator-associated pneumonia (VAP) in patients admitted to the intensive care unit for trauma. Genome-wide expression analysis may help to identify potential diagnostic markers for diseases. The current study examined the changes in blood transcriptome during VAP. Methods:The authors prospectively included 165 trauma patients, and 41 developed VAP. Whole blood samples were collected at admission and at VAP. To predict VAP, the admission samples were compared by microarray in patients who did or did not develop VAP. To identify diagnosis markers, paired samples of 35 patients who developed VAP were analyzed. Using NanoString (Seattle, WA), the results were confirmed in the patients who developed VAP. Trauma patients who did not develop VAP served as controls to eliminate a time effect. Results:The injury severity scores of the patients who did or did not develop VAP were 36 and 29, respectively. No predictive biomarker was identified. For patients who developed VAP, a transcriptional signature was identified between the two sampling times. However, this signature was a generalized pattern related to trauma, independent of the infectious process. Genes involved in the proinflammatory response were down-regulated in the patients who developed VAP, but this difference was not statistically significant. Conclusions:In contrast to clinical assessment, transcriptional analysis of whole blood samples cannot predict or diagnose VAP in trauma patients. Differentiating infection from inflammation seems challenging.