ArticleCritical care medicine2013
Innate immune function and mortality in critically ill children with influenza: a multicenter study.
Article in Critical care medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Surviving Sepsis Campaign International Guidelines for the Management of Sepsis and Septic Shock in Children 2026.Intensive care medicine · 2026Pooled it
- Immune System Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.Pediatrics · 2022Pooled it
- Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial.Critical care medicine · 2022Trial
- Evaluation of Mannose Binding Lectin Gene Variants in Pediatric Influenza Virus-Related Critical Illness.Frontiers in immunology · 2019Trial
- Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia.Critical care medicine · 2017Trial
- Candida in the respiratory tract secretions of critically ill patients and the impact of antifungal treatment: a randomized placebo controlled pilot trial (CANTREAT study).Intensive care medicine · 2014Trial
- Aberrant STAT signaling and T cell dysregulation define a targetable pediatric sepsis endotype.The Journal of clinical investigation · 2026Article
- Age-dependent immune landscapes affect influenza vaccine effectiveness and guide precision strategies.Frontiers in immunology · 2026Review
- Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.Pediatric research · 2025Review
- Mathematical Model of Influenza Infection Suggests JAK-STAT Activity Drives Severe Pathologies in Juvenile Mice.Frontiers in applied mathematics and statistics · 2025Article
- Ex Vivo Endotoxin Stimulation of Blood for Predicting Survival in Patients With Sepsis: A Systematic Review.CHEST critical care · 2023Article
- Comparison of whole blood cytokine immunoassays for rapid, functional immune phenotyping in critically ill patients with sepsis.Intensive care medicine experimental · 2023Article
- Interrogating the sepsis host immune response using cytomics.Critical care (London, England) · 2023Review
- Association of Asthma With Treatments and Outcomes in Children With Critical Influenza.The journal of allergy and clinical immunology. In practice · 2023Observational
- Pathobiology, Severity, and Risk Stratification of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2023Review
- Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.Frontiers in immunology · 2023Article
- Expression Patterns of Airway Fluid Cytokines From Intubated Children With Pediatric Acute Respiratory Distress Syndrome.Critical care explorations · 2022Article
- DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents.The Journal of infectious diseases · 2022Article
- Host Respiratory Transcriptome Signature Associated with Poor Outcome in Children with Influenza-Staphylococcus aureus Pneumonia.The Journal of infectious diseases · 2022Article
- Heterotypic Influenza Infections Mitigate Susceptibility to Secondary Bacterial Infection.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveTo prospectively evaluate relationships among serum cytokine levels, innate immune responsiveness, and mortality in a multicenter cohort of critically ill children with influenza infection.
designProspective, multicenter, observational study.
settingFifteen pediatric ICUs among members of the Pediatric Acute Lung Injury and Sepsis Investigators network. PATIENTS: Patients ≤18 yrs old admitted to a PICU with community-acquired influenza infection. A control group of outpatient children was also evaluated.
interventionsICU patients underwent sampling within 72 hrs of ICU admission for measurement of a panel of 31 serum cytokine levels and quantification of whole blood ex vivo lipopolysaccharide-stimulated tumor necrosis factor-α production capacity using a standardized stimulation protocol. Outpatient control subjects also underwent measurement of tumor necrosis factor-α production capacity. MEASUREMENTS AND MAIN
resultsFifty-two patients (44 survivors, eight deaths) were sampled. High levels of serum cytokines (granulocyte macrophage colony-stimulating factor, interleukin-6, interleukin-8, interferon-inducible protein-10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1α) were associated with mortality (p < 0.0016 for each comparison) as was the presence of secondary infection with Staphylococcus aureus (p = 0.007), particularly methicillin-resistant S. aureus (p < 0.0001). Nonsurvivors were immunosuppressed with leukopenia and markedly reduced tumor necrosis factor-α production capacity compared with outpatient control subjects (n = 21, p < 0.0001) and to ICU survivors (p < 0.0001). This association remained after controlling for multiple covariables. A tumor necrosis factor-α response <250 pg/mL was highly predictive of death and longer duration of ICU stay (p < 0.0001). Patients with S. aureus coinfection demonstrated the greatest degree of immunosuppression (p < 0.0001).
conclusionsHigh serum levels of cytokines can coexist with marked innate immune suppression in children with critical influenza. Severe, early innate immune suppression is highly associated with both S. aureus coinfection and mortality in this population. Multicenter innate immune function testing is feasible and can identify these high-risk children.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.