Evidence map›Paper›PMID 42387347›Full record

Observational studyCritical care (London, England)2026

Cytokine-based strategies to improve prognostic enrichment of pediatric ARDS.

E Scott Halstead, Todd M Umstead, Zissis C Chroneos, Cainan Riccio-Baum, S Rameeza Allie, Daniel J McKeone, Debbie Spear, Ryan A Nofziger, Ronald C Sanders, Danielle Ahn and 14 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Critical care (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04113434 (Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

NCT04113434 completednot on this map

Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

TypeobservationalSponsorChildren's Hospital of PhiladelphiaRan2020 to 2025Enrolled513ConditionsAcute Respiratory Distress Syndrome
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

E Scott HalsteadDivision of Pediatric Critical Care Medicine, Department of Pediatrics, Penn State College of Medicine, 500 University Drive, MC H085, Hershey, PA, 17033, USA. ehalstead@pennstatehealth.psu.edu.ORCID http://orcid.org/0000-0002-1167-0363
Todd M UmsteadDivision of Neonatal-Perinatal Medicine, Pulmonary Immunology and Physiology Laboratory, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Zissis C ChroneosDivision of Neonatal-Perinatal Medicine, Pulmonary Immunology and Physiology Laboratory, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Cainan Riccio-BaumDepartment of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA, USA.
S Rameeza AllieDepartment of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA, USA.
Daniel J McKeoneDivision of Pediatric Hematology-Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Debbie SpearDivision of Pediatric Critical Care Medicine, Department of Pediatrics, Penn State College of Medicine, 500 University Drive, MC H085, Hershey, PA, 17033, USA.
Ryan A NofzigerDepartment of Pediatrics, Division of Critical Care, Akron Children's Hospital, Akron, OH, USA.
Ronald C SandersSection of Critical Care, Department of Pediatrics, UAMS/Arkansas Children's Hospital, Little Rock, AR, USA.
Danielle AhnDepartment of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Jasmine C DowellMedical College of Wisconsin, Children's Wisconsin, Milwaukee, WI, USA.
Asdis F WagnerDepartment of Pediatrics, Children's Mercy Hospital, Kansas City, MO, USA.
Neal J ThomasDivision of Pediatric Critical Care Medicine, Department of Pediatrics, Penn State College of Medicine, 500 University Drive, MC H085, Hershey, PA, 17033, USA.
Prithvi SendiDivision of Critical Care Medicine, Nicklaus Children's Hospital, Miami, FL, USA.
W Joshua FrazierDivision of Critical Care Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Courtney M RowanDepartment of Pediatrics, Division of Pediatric Critical Care Medicine, Indiana University School of Medicine and Riley Hospital for Children at IU Health, Indianapolis, IN, USA.
Parag N JainDepartment of Pediatrics, Divisions of Pediatric Cardiology and Critical Care, UT Southwestern Medical Center and Children's Health, Dallas, TX, USA.
Dalia A BashirDivision of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
Stuart H FriessDepartment of Pediatrics, Washington University in St Louis, St Louis, MO, USA.
Brian M VariscoDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Jocelyn GrunwellDepartment of Pediatrics, Emory University, Children's Healthcare of Atlanta - Arthur M. Blank Hospital, Atlanta, GA, USA.
Aline B MadduxDepartments of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
Stephen T FamularoDivision of Critical Care Medicine, Department of Anesthesia and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Nadir YehyaDivision of Critical Care Medicine, Department of Anesthesia and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Funding

Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress SyndromeR01HL148054 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI YEHYA, NADIR · 2019 to 2023
$4.1M
NHLBI NIH HHS R01 HL148054NHLBI NIH HHS R01HL148054
6 · The paper itself

Abstract

backgroundHyper-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.

methodsWe 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™).

resultsThe 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.

conclusionsCytokine-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.

trial registrationClinical Trial NCT04113434 was registered 2019-10-02.

Indexed as

CytokinesRespiratory Distress SyndromeAdolescentBiomarkersChildChild, PreschoolCohort StudiesFemaleHumansInterleukin-6MalePrognosisProspective StudiesReceptors, Tumor Necrosis Factor, Type IBiomarkersCytokinesInterleukin-6Receptors, Tumor Necrosis Factor, Type I

Identifiers

PMID42387347
PMCPMC13591932

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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.