title: Preliminary evidence for leukocyte transcriptional signatures for pediatric ventilator-associated pneumonia.
abstract: OBJECTIVE
  Ventilator-associated pneumonia (VAP) is a significant contributor to intensive care unit (ICU) morbidity and mortality and presents a significant diagnostic challenge. Our hypothesis was that blood RNA expression profiles can be used to track the response to VAP in children, using the same methods that proved informational in adults.
  
  
  METHODS
  A pilot, nonrandomized, repeated measures case-control study of changes in the abundance of total RNA in buffy coat and clinical scores for VAP.
  
  
  METHODS
  A large, multispecialty university-based pediatric ICU and cardiac ICU.
  
  
  METHODS
  Seven children requiring intubation and mechanical ventilation.
  
  
  METHODS
  Blood samples were drawn at time of enrollment and every 48 hours for a maximum of 11 samples (21 days). Patients ranged in age from 1 to 18 months (mean 8 months). All patients survived to the end of the study. Of the 7 patients studied, 4 developed VAP.
  
  
  RESULTS
  Statistical analysis of the Affymetrix Human Genome Focus GeneChip signal was conducted on normalized expression values of 8793 probe sets using analysis of variance (ANOVA) with a false discovery rate of 0.10. The expression patterns of 48 genes appeared to discriminate between the 2 classes of ventilated children: those with and those without pneumonia. Gene expression network analysis revealed several gene ontologies of interest, including cell proliferation, differentiation, growth, and apoptosis, as well as genes not previously implicated in sepsis.
  
  
  CONCLUSIONS
  These preliminary data are the first in critically ill children supporting the hypothesis that there is a detectable VAP signal in gene expression profiles. Larger studies are needed to validate these preliminary findings and test the diagnostic value of longitudinal changes in leukocyte RNA signatures.
authors: The Department of Pediatrics, St. Louis University School of Medicine, St. Louis, MO 63110, USA. jwerner2@slu.edu
authors: Jason A
authors: JA
authors: Werner
authors: William
authors: W
authors: Schierding
authors: David
authors: D
authors: Dixon
authors: Sandra
authors: S
authors: MacMillan
authors: Douglas
authors: D
authors: Oppedal
authors: Jared
authors: J
authors: Muenzer
authors: J Perren
authors: JP
authors: Cobb
authors: Paul A
authors: PA
authors: Checchia