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Published on: April 7, 2021
Incorporating Inflammation into Mortality Risk in Pediatric Acute Respiratory Distress Syndrome
Matt S Zinter1, Benjamin E Orwoll, Aaron C Spicer
11Division of Critical Care, Department of Pediatrics, UCSF School of Medicine, Benioff Children's Hospital, San Francisco, CA. 2Departments of Medicine and Anesthesia, UCSF School of Medicine, Cardiovascular Research Institute, San Francisco, CA. 3Division of Critical Care, Department of Pediatrics, UCLA Geffen School of Medicine, Mattel Children's Hospital, Los Angeles, CA.
Insights
Elevated pro- and anti-inflammatory cytokines in pediatric acute respiratory distress syndrome are linked to higher mortality and ICU morbidity. These biomarkers improve risk prediction for poor outcomes in children.
Area of Science:
- Pediatric Critical Care Medicine
- Immunology
- Respiratory Medicine
Background:
- Pediatric acute respiratory distress syndrome (PARDS) involves severe lung injury driven by immune activation and inflammation.
- Identifying reliable biomarkers for PARDS prognosis is crucial for effective patient management.
Purpose of the Study:
- To investigate the association between pro- and anti-inflammatory cytokines and mortality in pediatric acute respiratory distress syndrome (PARDS).
- To determine if these cytokine biomarkers can enhance the risk stratification of poor outcomes in PARDS patients.
Main Methods:
- A multicenter prospective observational study involving 194 pediatric patients with PARDS.
- Measured eight pro- and anti-inflammatory cytokines on day 1 of PARDS, correlating them with mortality, ICU morbidity (Pediatric Logistic Organ Dysfunction score), and endothelial injury markers.
- Utilized logistic regression models to assess predictive capabilities.
Main Results:
- Elevated levels of Interleukin-6, Interleukin-8, Interleukin-10, Interleukin-18, and Tumor Necrosis Factor-R2 were strongly associated with mortality, ICU morbidity, and endothelial injury.
- A predictive model incorporating oxygenation index, Interleukin-8, and Tumor Necrosis Factor-R2 demonstrated superior accuracy in predicting mortality or severe morbidity compared to oxygenation index alone (AUC 0.77 vs 0.70).
Conclusions:
- Pro- and anti-inflammatory cytokines are significant predictors of mortality, ICU morbidity, and endothelial injury in pediatric acute respiratory distress syndrome (PARDS).
- These cytokine biomarkers substantially improve the risk stratification capabilities of the oxygenation index for predicting adverse outcomes in PARDS.
- Cytokine profiling may aid in identifying high-risk pediatric patients for targeted therapeutic strategies and clinical trial enrollment.
Objectives:
In pediatric acute respiratory distress syndrome, lung injury is mediated by immune activation and severe inflammation. Therefore, we hypothesized that patients with elevated pro- and anti-inflammatory cytokines would have higher mortality rates and that these biomarkers could improve risk stratification of poor outcomes.
Design:
Multicenter prospective observational study.
Setting:
We enrolled patients from five academic PICUs between 2008 and 2015.
Patients:
Patients were 1 month to 18 years old, used noninvasive or invasive ventilation, and met the American European Consensus Conference definition of acute respiratory distress syndrome.
Interventions:
Eight proinflammatory and anti-inflammatory cytokines were measured on acute respiratory distress syndrome day 1 and correlated with mortality, ICU morbidity as measured by survivor Pediatric Logistic Organ Dysfunction score, and biomarkers of endothelial injury, including angiopoietin-2, von Willebrand Factor, and soluble thrombomodulin.
Measurements And Main Results:
We measured biomarker levels in 194 patients, including 38 acute respiratory distress syndrome nonsurvivors. Interleukin-6, interleukin-8, interleukin-10, interleukin-18, and tumor necrosis factor-R2 were each strongly associated with all-cause mortality, multiple markers of ICU morbidity, and endothelial injury. A multiple logistic regression model incorporating oxygenation index, interleukin-8, and tumor necrosis factor-R2 was superior to a model of oxygenation index alone in predicting the composite outcome of mortality or severe morbidity (area under the receiver operating characteristic, 0.77 [0.70-0.83] vs 0.70 [0.62-0.77]; p = 0.042).
Conclusions:
In pediatric acute respiratory distress syndrome, pro- and anti-inflammatory cytokines are strongly associated with mortality, ICU morbidity, and biochemical evidence of endothelial injury. These cytokines significantly improve the ability of the oxygenation index to discriminate risk of mortality or severe morbidity and may allow for identification and enrollment of high-risk subgroups for future studies.
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