Metabolomics in pediatric lower respiratory tract infections and sepsis: a literature review

Wildman, Emily; Mickiewicz, Beata; Vogel, Hans J.; Thompson, Graham

doi:10.1038/s41390-022-02162-0

“…Wildman et al 24 . reviewed the above studies at the metabolic level in children with sepsis and found that three metabolites (3‐hydroxybutyrate, glucose, and acetone) overlapped in these findings, suggesting that these three metabolites may be promising biomarkers targets for further clinical validation.…”

Section: Biomarkers Screened By Metabolomicsmentioning

confidence: 99%

“…Several studies have previously summarized the progress of research on sepsis markers in children. 3,[18][19][20][21][22][23][24][25] In this study, we reviewed the research progress about pediatric sepsis markers from different levels according to the omics tools used for biomarker identification. Since the neonatal immune response against sepsis is different from that of children, sepsis biomarkers screened by using neonatal samples were not included in this review.…”

Section: Introductionmentioning

confidence: 99%

“…The application of machine learning in studying sepsis biomarkers and the establishment of a model in assessing the risk of death from septic shock could also help to promote the finding of novel biomarkers for sepsis diagnosis and prognosis. Several studies have previously summarized the progress of research on sepsis markers in children 3,18–25 …”

Section: Introductionmentioning

confidence: 99%

“…Several studies have previously summarized the progress of research on sepsis markers in children. 3 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 …”

Section: Introductionmentioning

confidence: 99%

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Multilevel omics for the discovery of biomarkers in pediatric sepsis

Wang,

Li,

Qian

et al. 2023

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Severe sepsis causes organ dysfunction and continues to be the leading reason for pediatric death worldwide. Early recognition of sepsis could substantially promote precision treatment and reduce the risk of pediatric death. The host cellular response to infection during sepsis between adults and pediatrics could be significantly different. A growing body of studies focused on finding markers in pediatric sepsis in recent years using multi‐omics approaches. This narrative review summarized the progress in studying pediatric sepsis biomarkers from genome, transcript, protein, and metabolite levels according to the omics technique that has been applied for biomarker screening. It is most likely not a single biomarker could work for precision diagnosis of sepsis, but a panel of markers and probably a combination of markers detected at multi‐levels. Importantly, we emphasize the importance of group distinction of infectious agents in sepsis patients for biomarker identification, because the host response to infection of bacteria, virus, or fungus could be substantially different and thus the results of biomarker screening. Further studies on the investigation of sepsis biomarkers that were caused by a specific group of infectious agents should be encouraged in the future, which will better improve the clinical execution of personalized medicine for pediatric sepsis.

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Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections

Lydon,

Osborne,

Wagner

et al. 2024

Preprint

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Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses to severe pediatric vLRTI in both the lower airway and systemic circulation. To address this gap, gain insights into vLRTI pathophysiology, and test a novel diagnostic approach, we assayed 1,305 proteins in tracheal aspirate (TA) and plasma from 62 critically ill children using SomaScan. We performed differential expression (DE) and pathway analyses comparing vLRTI (n=40) to controls with non-infectious acute respiratory failure (n=22), developed a diagnostic classifier using LASSO regression, and analyzed matched TA and plasma samples. We further investigated the impact of viral load and bacterial coinfection on the proteome. The TA signature of vLRTI was characterized by 200 DE proteins (Padj<0.05) with upregulation of interferons and T cell responses and downregulation of inflammation-modulating proteins including FABP and MIP-5. A nine-protein TA classifier achieved an AUC of 0.96 (95% CI 0.90-1.00) for identifying vLRTI. In plasma, the host response to vLRTI was more muted with 56 DE proteins. Correlation between TA and plasma was limited, although ISG15 was elevated in both compartments. In bacterial coinfection, we observed increases in the TNF-stimulated protein TSG-6, as well as CRP, and interferon-related proteins. Viral load correlated positively with interferon signaling and negatively with neutrophil-activation pathways. Taken together, our study provides fresh insight into the lower airway and systemic proteome of severe pediatric vLRTI, and identifies novel protein biomarkers with diagnostic potential.

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Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections

Lydon,

Osborne,

Wagner

et al. 2024

mSystems

0

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Viral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses to severe pediatric vLRTI in both the lower airway and systemic circulation. To address this gap, gain insights into vLRTI pathophysiology, and test a novel diagnostic approach, we assayed 1,305 proteins in tracheal aspirate (TA) and plasma from 62 critically ill children using SomaScan. We performed differential expression (DE) and pathway analyses comparing vLRTI ( n = 40) to controls with non-infectious acute respiratory failure ( n = 22), developed a diagnostic classifier using LASSO regression, and analyzed matched TA and plasma samples. We further investigated the impact of viral load and bacterial coinfection on the proteome. The TA signature of vLRTI was characterized by 200 DE proteins (P adj <0.05) with upregulation of interferons and T cell responses and downregulation of inflammation-modulating proteins including FABP and MIP-5. A nine-protein TA classifier achieved an area under the receiver operator curve (AUC) of 0.96 (95% CI: 0.90–1.00) for identifying vLRTI. In plasma, the host response to vLRTI was more muted with 56 DE proteins. Correlation between TA and plasma was limited, although ISG15 was elevated in both compartments. In bacterial coinfection, we observed increases in the TNF-stimulated protein TSG-6, as well as CRP, and interferon-related proteins. Viral load correlated positively with interferon signaling and negatively with neutrophil-activation pathways. Taken together, our study provides fresh insights into the lower airway and systemic proteome of severe pediatric vLRTI and identifies novel protein biomarkers with diagnostic potential. IMPORTANCE We describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated a positive correlation with interferon-related protein expression and a negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insights into the lower airway and systemic proteome of severe pediatric vLRTI.

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Metabolomics in pediatric lower respiratory tract infections and sepsis: a literature review

Cited by 7 publications

References 85 publications

Multilevel omics for the discovery of biomarkers in pediatric sepsis

Multilevel omics for the discovery of biomarkers in pediatric sepsis

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections

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