# Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $831,661

## Abstract

PROJECT SUMMARY/ABSTRACT
Acute respiratory distress syndrome (ARDS) is characterized by acute onset of diffuse, bilateral pulmonary
edema and severe hypoxemia not fully explained by cardiac failure. The syndrome affects 45,000 children in
the United States annually, representing 10% of mechanically ventilated children in pediatric intensive care
units (PICUs), with an associated mortality rate of up to 20%. There are no specific pharmacological therapies
for ARDS despite several trials, and supportive care remains the mainstay of treatment. In children, a lack of
therapies is further compounded by uncertainty in management, as guidelines are typically extrapolated from
adult ARDS, with uncertain applicability. However, pediatric ARDS possesses a distinct epidemiologic and
outcome profile, necessitating studies specific to this population. Given the heterogeneity of ARDS,
biomarkers have been proposed to aid in diagnosis, improve risk stratification, and identify endogenous sub-
phenotypes (endotypes) with shared pathophysiologic, biomarker, or transcriptomic profiles. Risk stratification
and endotype identification are essential for improved patient selection for trials of targeted therapies,
particularly for targeted therapies beyond supportive care. However, the absence of well-powered cohorts with
biomarker data leaves a knowledge gap regarding the existence and clinical relevance of endotypes in
pediatric ARDS. This proposal builds off of Dr. Yehya’s experience with plasma biomarkers and whole blood
transcriptomics in pediatric ARDS obtained during his K23 award to perform prospective risk stratification and
endotype identification in 500 children with ARDS from 12 PICUs in the United States. The specific goals are
to 1) validate PARDSEVERE, a multiple biomarker-based risk stratification tool in pediatric ARDS; 2) test
whether a known 100-gene classifier identifies transcriptomic endotypes in pediatric ARDS; and 3) use
clustering methodology to identify novel plasma biomarker- and mRNA-based endotypes. These studies are
the first steps towards prognostic enrichment (selecting subjects with worse prognosis for trials) and predictive
enrichment (selecting subjects likely to respond to a trial intervention) for future pediatric ARDS trials. The
proposed studies will validate a risk stratification tool for pediatric ARDS and identify endotypes with shared
biology in order to more appropriately target therapies in future trials. The proposal leverages the existing
infrastructure and extensive expertise at the Children’s Hospital of Philadelphia, the University of Pennsylvania,
and Cincinnati Children’s Hospital Medical Center. Overall, these studies are a significant advance for the field
of pediatric ARDS, represent a tremendous resource for future studies, and form the basis for the next
generation of interventional trials using enrichment strategies to mitigate heterogeneity.

## Key facts

- **NIH application ID:** 9944669
- **Project number:** 5R01HL148054-02
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Nadir Yehya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $831,661
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944669

## Citation

> US National Institutes of Health, RePORTER application 9944669, Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome (5R01HL148054-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944669. Licensed CC0.

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