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Updated: Jun 1, 2026

Murine Oropharyngeal Aspiration Model of Ventilator-associated and Hospital-acquired Bacterial Pneumonia
Published on: June 28, 2018
Preliminary evidence for leukocyte transcriptional signatures for pediatric ventilator-associated pneumonia
Jason A Werner1, William Schierding, David Dixon
1The Department of Pediatrics, St. Louis University School of Medicine, St. Louis, MO 63110, USA. jwerner2@slu.edu
Insights
Blood RNA expression profiles show promise for tracking ventilator-associated pneumonia (VAP) in children. These preliminary findings suggest a detectable VAP signal in gene expression, warranting further investigation.
Area of Science:
- Pediatric critical care medicine
- Molecular diagnostics
- Genomics
Background:
- Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in pediatric intensive care units (ICUs).
- Diagnosing VAP in children presents significant challenges.
- Previous studies in adults suggested blood RNA expression profiles could aid in VAP detection.
Purpose of the Study:
- To investigate the potential of blood RNA expression profiles for monitoring VAP response in children.
- To determine if gene expression patterns can differentiate between ventilated children with and without VAP.
Main Methods:
- A pilot, nonrandomized, repeated measures case-control study.
- Analysis of blood RNA abundance in buffy coat samples from 7 mechanically ventilated children (1-18 months old).
- Gene expression profiling using Affymetrix Human Genome Focus GeneChip and statistical analysis (ANOVA).
Main Results:
- Expression patterns of 48 genes differentiated between children with and without VAP.
- Gene expression network analysis identified pathways related to cell proliferation, differentiation, growth, and apoptosis.
- Several novel genes implicated in sepsis were identified.
Conclusions:
- Preliminary data support the hypothesis that a detectable VAP signal exists in blood gene expression profiles of critically ill children.
- These findings are the first to demonstrate this in a pediatric population.
- Larger studies are needed to validate these results and assess the diagnostic utility of longitudinal RNA signatures.
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.
Design:
A pilot, nonrandomized, repeated measures case-control study of changes in the abundance of total RNA in buffy coat and clinical scores for VAP.
Setting:
A large, multispecialty university-based pediatric ICU and cardiac ICU.
Patients:
Seven children requiring intubation and mechanical ventilation.
Interventions:
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.
Measurements And Main 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.
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