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Updated: Aug 8, 2025

Murine Oropharyngeal Aspiration Model of Ventilator-associated and Hospital-acquired Bacterial Pneumonia
Published on: June 28, 2018
Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia
Yi Wang1, Xiaolan Huang2, Fang Li3
1Experimental Research Center, Capital Institute of Pediatrics, Beijing, 100020, People's Republic of China. wildwolf0101@163.com.
Insights
New biomarkers for severe community-acquired pneumonia (CAP) in children were identified using proteomics and metabolomics. This integrated approach aids in early diagnosis and understanding CAP severity mechanisms.
Area of Science:
- Pediatric Infectious Diseases
- Biomarker Discovery
- Systems Biology
Background:
- Community-acquired pneumonia (CAP) is a leading cause of mortality in children under five globally.
- Early diagnosis and understanding the mechanisms of severe CAP are crucial for improving outcomes.
Purpose of the Study:
- To identify novel early biomarkers for severe CAP.
- To elucidate the underlying pathological mechanisms contributing to CAP severity in children.
Main Methods:
- Integrated proteomic and metabolomic analysis of serum samples from severe CAP, non-severe CAP, and healthy control cohorts.
- Validation of identified biomarkers using ELISA and metabolomics in an independent cohort.
- Pathway analysis to explore molecular mechanisms of disease severity.
Main Results:
- Distinct proteomic and metabolic signatures differentiated severe CAP, non-severe CAP, and controls.
- A novel biomarker panel including C-reactive protein (CRP), lipopolysaccharide (LBP), and three metabolites was developed for CAP identification and severity assessment.
- Pathway analysis revealed dysregulation in cell death, complement system, coagulation, platelet function, inflammation, glycolysis, and lipid metabolism in severe CAP.
Conclusions:
- Integrated proteomic and metabolomic analysis offers a promising approach for diagnosing CAP and understanding its severity.
- The identified biomarkers and pathways provide new insights into the complex pathogenesis of severe CAP in children.
Objective:
Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity.
Methods:
Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP.
Results:
The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP.
Conclusion:
The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.
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