What question did this study set out to answer?

This research aims to enhance the prognostic accuracy for pediatric ARDS using cytokine-based models.

July 3, 2026Critical Care0 citationsOpen Access

Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS

EHE. Scott HalsteadPenn State Milton S. Hershey Medical Center TUTodd M. UmsteadPennsylvania State University ZCZissis C. ChroneosPennsylvania State University

Key Points

This research aims to enhance the prognostic accuracy for pediatric ARDS using cytokine-based models.
Prospective multicenter cohort study of 500 children with ARDS (NCT04113434).
Plasma samples collected within 24 hours of ARDS onset for cytokine measurement using microfluidic immunoassay.
Evaluation of traditional and new cytokine models for 90-day mortality prediction.
Traditional three-term model showed modest utility for predicting 90-day mortality (AUC 0.62).
CCL7 was significantly associated with mortality (p < 0.0001) and improved prognostic models (AUROCs 0.72–0.73).
Immune compromised status was independently linked to increased mortality (p < 0.0001).

Abstract

Hyper-inflammation is common to multiple critical care syndromes, including acute respiratory distress syndrome (ARDS) and sepsis, and is associated with worse outcomes. A signature of hyper-inflammatory ARDS has been described in adults using IL-6, TNFR1, and bicarbonate, and has prognostic utility. We investigated the application of this traditional parsimonious signature to pediatric ARDS patients and tested whether we could improve prognostic enrichment using other cytokines. We leveraged a prospective multicenter cohort study of 500 children with ARDS (Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome LEOPARDS; NCT04113434) study. Plasma samples were obtained within 24 h of ARDS. Cytokines were measured using microfluidic immunoassay (Ella™). The traditional 3-term (IL-6, TNFR1, and bicarbonate) hyper-/hypo-inflammatory phenotype model demonstrated modest utility for 90-day mortality (AUC 0.62, sensitivity 26%, positive predictive value PPV 24%) in LEOPARDS (14% hyper-inflammatory, 13.4% 90-day mortality). Of the additional cytokine biomarkers tested, CCL7 (MCP-3) demonstrated the most significant association with 90-day mortality ( p < 0.0001). Parsimonious two-term (CCL7, IL-18) and three-term models (CCL7, IL-18, TNFR1) demonstrated mortality discrimination in both training ( n = 300) (AUROCs 0.72–0.73) and validation ( n = 200) (AUROCs 0.66) sets, with improved net reclassification (~ 40% improved classification). Immune compromised status was independently associated with 90-day mortality ( p < 0.0001) with evidence that the optimal prognostic model may vary by immunocompromised status. Cytokine-based prognostic enrichment strategies show promise for children with ARDS. In addition to models based primarily on IL-6 and TNFR1, models including CCL7 and IL-18 may be of utility for assessing the full spectrum of inflammation. Future studies should focus on identifying whether cytokine-based enrichment can identify specific pathways to inform immunomodulatory interventions. Clinical Trial NCT04113434 was registered 2019-10-02.

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Halstead et al. (Wed,) studied this question.

synapsesocial.com/papers/6a47518c5c29257aa2578b23 https://doi.org/https://doi.org/10.1186/s13054-026-06174-8

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