# The Roles of Pulmonary Hypertension and Right Ventricular Dysfunction in Pediatric Acute Respiratory Distress Syndrome

> **NIH NIH K23** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $172,771

## Abstract

PROJECT SUMMARY
Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia and pulmonary edema not
fully explained by cardiac dysfunction or fluid overload. This syndrome affects 45,000 children annually in the
United States; the mortality rate is 20% in the United States and 30% worldwide. Pediatric ARDS morbidity and
mortality are primarily mediated through cardiovascular dysfunction with subsequent organ failure rather than
lung injury itself. There are no specific pharmacologic therapies for adult or pediatric ARDS despite numerous
trials that have mainly targeted improving oxygenation. Pediatric ARDS pathophysiology itself and treatments
such as high positive end-expiratory pressure and permissive hypercapnia contribute to the development of
pulmonary vascular dysfunction (leading to pulmonary hypertension) and right ventricular systolic dysfunction
(RV dysfunction). Pulmonary hypertension is a risk factor for RV dysfunction and RV dysfunction causes
impaired systemic cardiac output and, therefore, exacerbates multi-organ dysfunction. Thus, studies to define
the roles of pulmonary hypertension and RV dysfunction in ARDS outcomes are needed. Two-dimensional
speckle tracking echocardiography (or strain echo) is a sensitive indicator of RV dysfunction. Recent evidence
suggests that RV dysfunction (as measured by strain echo) and pulmonary hypertension are associated with
worse patient outcomes in pediatric ARDS. In addition, plasma-based biomarkers of RV dysfunction and
pulmonary endothelial injury may help to detect and predict these cardiovascular abnormalities. The proposed
study leverages existing infrastructure at the Children’s Hospital of Philadelphia and University of Pennsylvania
to conduct a prospective longitudinal cohort study using serial echocardiography and plasma biomarker
assessments over the first week following pediatric ARDS onset. A diverse and experienced mentorship and
collaborative team, with expertise in translational and clinical research, has been assembled. They will provide
guidance for the candidate through a rigorous training plan involving research conduct, didactics in advanced
epidemiological analyses, training in echocardiographic methods, and intensive mentorship. The proposed
studies will define the clinical impact of RV dysfunction and pulmonary hypertension and investigate the role of
a novel biomarker of pulmonary endothelial damage in 250 patients with pediatric ARDS. Given the importance
of cardiovascular dysfunction in pediatric ARDS outcomes, cluster analyses will be used to classify patients
into cardiovascular subphenotypes that will be used in future studies for risk stratification and to test targeted
therapies to improve patient outcomes. Finally, the candidate will gain the necessary training in clinical
research, echocardiography, and biomarkers to mature into an independent clinician-scientist working to
improve outcomes for critically ill and injured children.

## Key facts

- **NIH application ID:** 10834099
- **Project number:** 5K23HL153759-04
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Adam S. Himebauch
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $172,771
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834099

## Citation

> US National Institutes of Health, RePORTER application 10834099, The Roles of Pulmonary Hypertension and Right Ventricular Dysfunction in Pediatric Acute Respiratory Distress Syndrome (5K23HL153759-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10834099. Licensed CC0.

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