What question did this study set out to answer?

The research aims to enhance prognostic models for pediatric ARDS by incorporating additional cytokines.

May 20, 2026

A26-10 Cytokine-Based Strategies to Improve Prognostic Enrichment of Pediatric Critical Illness Syndromes

Key Points

The research aims to enhance prognostic models for pediatric ARDS by incorporating additional cytokines.
Utilized a multicenter cohort study of 500 children with ARDS (NCT04113434).
Measured cytokines via microfluidic immunoassay (Ella™).
Conducted preclinical studies with C57BL/6J mice to observe cytokine signaling interactions.
Traditional hyper-inflammatory phenotype model had an AUC of 0.62 for 90-day mortality with 26% sensitivity.
A four-term model with IL-6, TNFR1, CXCL9, IL-18 showed improved AUC of 0.69 with 56% sensitivity.
In hypo-inflammatory ARDS, median IL-18 levels indicated differential mortality (log-rank p = 0.05).

Abstract

Abstract Introduction Hyperinflammation is common to critical care syndromes, including sepsis and acute respiratory distress syndrome (ARDS), and is associated with worse outcomes. A parsimonious signature of hyperinflammatory ARDS has been described using IL-6, TNFR1, and bicarbonate, with prognostic utility in pediatric ARDS. We aimed to determine whether the addition of CXCL9 and IL-18, which are elevated in hyperinflammatory conditions such as hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS), could improve on the prognostic model. Methods 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. Cytokines were measured using microfluidic immunoassay (Ella™). In preclinical studies, mouse recombinant cytokines were injected retro-orbitally into C57BL/6J mice, and serial cytokine measurements obtained were obtained by tail bleeds. Mouse cytokines were measured by Ella or singleplex ELISA. Results The traditional 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% hyperinflammatory; 9% mortality). In children with hypo-inflammatory ARDS, stratification by median IL-18 levels showed differential mortality (log-rank p = 0.05). A four-term model (IL-6, TNFR1, CXCL9, IL-18) had AUC 0.69 (sensitivity 56%. PPV 23%). Preclinical mouse models of cytokine-induced inflammation demonstrated that IL-6 levels were primarily a marker of synergistic IL-1 and TNF signaling activity. Conclusions Cytokine-based prognostic enrichment shows promise for children with critical illness syndromes, including ARDS and sepsis. Future studies should focus on identifying whether cytokine-based enrichment can identify specific pathways to inform immunomodulatory interventions. This abstract is funded by: NIH NHLBI (R01HL148054)

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Cite This Study

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

synapsesocial.com/papers/6a0d4fd2f03e14405aa9b49e https://doi.org/https://doi.org/10.1093/ajrccm/aamag162.027

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