Validation of the riboleukogram to detect ventilator-associated pneumonia after severe injury.

Objective: We hypothesized that circulating leukocyte RNA profiles or 'riboleukograrns" detect ventulator-associaied pneumonia after blunt trauma Summary Background Data: A pilot microarray Study of 11 ventilator-associated pneumonia (VAP) patients suggested that 85 leukocyte genes can be used to diagnose VAII. Validation of this gene set to detect VAP was tested using data from an independent patient cohort Methods: A total of 158 intubated blunt trauma patients were enrolled at 5 centers. where 57 (36%) developed VAP. Patient age was 34.2 +/- 11.1 years. 65% were male Circulating leukocyte GeneChip U 133 2 0 expression values were measured at time 0.5. 1, 4, 7, 14, 21 and 28 days after injury DChip normalized leukocyte transcriptional profiles were analyzed using repeated measures logistic regression A compound covariate model based on leukocyte gene transcriptional profiles in a training subset of patients was tested to determine predictive accuracy for VAII 4 days prior to (clinical diagnosis in the test subset. Results: Using gene expression values measured on each study (lay at all FDR <0.05, 27 (32%) of the 85 genes were associated with Lhe diagnosis of VAP 1 to 4 days before diagnosis However, the compound covariate model based on these 85-genes did not predict VAP in the test cohort better than chance (P = 027) 111 contrast, a compound covariate model based upon de novo transcriptional analysis of the 158 patients predicted VAP better than chance 4 days before diagnosis with a sensitivity of 57% and a specificity of 69%. Conclusion: Our results validate those described in I pilot study, confirming that riboleukograms are associated with the development of VAP days prior to clinical diagnosis Similarly. a riboleukogram predictive model tested oil a larger cohort of 158 patients was better than chance at predicting VAP (lays prior to clinical diagnosis