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

Award Number: K23HL153759
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $176,799 )
2025	2025	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Lung Diseases Research	000	5	4/1/2025	NON-COMPETING CONTINUATION	$176,799
														Subtotal = $176,799

Issue Date FY: 2024 ( Subtotal = $172,771 )
2024	2024	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Lung Diseases Research	000	4	4/3/2024	NON-COMPETING CONTINUATION	$172,771
														Subtotal = $172,771

Issue Date FY: 2023 ( Subtotal = $174,299 )
2023	2023	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Lung Diseases Research	000	3	4/28/2023	NON-COMPETING CONTINUATION	$174,299
														Subtotal = $174,299

Issue Date FY: 2022 ( Subtotal = $176,305 )
2022	2022	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Lung Diseases Research	000	2	5/20/2022	NON-COMPETING CONTINUATION	$176,305
														Subtotal = $176,305

Issue Date FY: 2021 ( Subtotal = $178,597 )
2021	2021	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Lung Diseases Research	000	1	4/9/2021	NEW	$178,597
														Subtotal = $178,597

Grand Total All Awards = $878,771

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

Award Number: K23HL153759

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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