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Published on: August 7, 2017
Predicting infectious etiology and severity in hospitalized pediatric pneumonia using blood cytokine biomarkers
Alexis M Duray1, Benjamin Lee1, Robert N Abood1
1Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States.
Insights
Cytokine levels in children with pneumonia can predict disease severity and type. Specific cytokines like CHI3L1 and IL-6 help differentiate viral from bacterial pneumonia and forecast outcomes.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Biomarker Discovery
Background:
- Lower respiratory infections pose a significant global health burden in children, contributing to substantial morbidity and mortality.
- Understanding the host immune response is crucial for predicting disease progression and outcomes in pediatric pneumonia.
Purpose of the Study:
- To investigate the predictive value of plasma cytokine levels at hospital admission for disease etiology and severity in pediatric lower respiratory infections.
- To identify specific cytokine profiles associated with different viral pathogens and disease severity outcomes, including hospitalization duration, intensive care unit (ICU) admission, and hypoxemia.
Main Methods:
- Plasma samples were collected from 159 pediatric inpatients diagnosed with lower respiratory infections.
- Cytokine levels were quantified using multiplex analyses, with 59 cytokines assessed.
- Logistic regression and machine learning models were employed to correlate cytokine concentrations with clinical outcomes such as prolonged hospitalization (≥5 days), ICU admission, and hypoxemia (SpO2 < 90%).
Main Results:
- Human rhinovirus/enterovirus (hRV/EV), respiratory syncytial virus (RSV), and influenza virus were the most common viral culprits.
- Elevated levels of CHI3L1, IL-1Rα, IL-6, G-CSF, MCP-1, and MIP-1α were associated with severe pneumonia, irrespective of the causative agent.
- Distinct cytokine patterns, including a type-2 immune response, predicted disease duration in RSV cases.
- Specific cytokines like CHI3L1, pentraxin-3, osteopontin, and IL-20 correlated with severity across various etiologies.
- IL-6, MMP-2, and LIGHT differentiated viral from community-acquired pneumonia (CAP).
- In influenza, CHI3L1 and sTNFR1 predicted longer hospitalization and ICU admission; RSV severity correlated with MIP-1α, IL-26, G-CSF, and IFNβ.
Conclusions:
- Plasma cytokine profiles exhibit heterogeneity in severe pediatric pneumonia, offering insights into distinct immune responses.
- Identified cytokine groupings can potentially distinguish between viral and non-viral pneumonia etiologies.
- These findings may lead to improved diagnostic and prognostic tools for pediatric respiratory infections based on host immune markers.
Background:
Lower respiratory infections are a significant cause of morbidity and mortality in children. The aim of this study was to determine whether cytokine levels measured in plasma at the time of admission to the hospital can predict disease etiology or severity.
Methods:
Blood was collected from pediatric inpatients, and cytokine levels were determined by cytokine multiplex analyses. Plasma cytokine concentrations were then analyzed using logistic regression and machine learning approaches to determine if we could accurately predict if a child would require longer-term hospitalization (≥5 days), intensive care, or exhibit hypoxemia (SpO2 < 90%).
Results:
A total of 159 patients were enrolled, and 59 cytokines were assessed in relation to the type of infection and severity. The most prevalent viral infections were human rhinovirus/enterovirus (hRV/EV; 24.4%), respiratory syncytial virus (RSV; 21.8%), and influenza virus (16.7%). Several cytokines (CHI3L1, IL-1Rα, IL-6, G-CSF, MCP-1, and MIP-1α) were elevated in severe pneumonia cases, regardless of disease etiology. Predictors of duration in RSV cases were distinct from other causes, with a predominance of type-2 immune response. Cytokines such as chitinase-3-like-1 (CHI3L1), pentraxin-3, osteopontin, and IL-20 correlated with severity across multiple groups. Plasma levels of IL-6, MMP-2 and LIGHT could be employed to separate viral vs. community acquired pneumonia (CAP). In influenza cases, longer-term hospitalization and ICU admission could be predicted based on two cytokines, CHI3L1 and sTNFR1. RSV severity was closely correlated with levels of MIP-1α, IL-26, G-CSF, and IFNβ.
Conclusions:
This study highlights the heterogeneity of immune responses to severe pneumonia and provides new groupings of cytokines which may distinguish between viral and non-viral pneumonia.
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