Pediatric pulmonary vascular diseases (PVD), including pediatric pulmonary hypertension (PH), are high morbidity and mortality conditions, yet treatment options are limited. Despite new drug therapies, survival of patients with severe PH remains poor. Although most clinical studies have emphasized disease in adults, pediatric PVD can be devastating, contributing substantially to poor outcomes in newborns, infants and children that are strikingly different from those encountered in adults. Unfortunately, very few studies have addressed the safety and efficacy of PVD therapies in children. Current approaches to PVD are limited by small numbers of patients with PH and the association of PH with a variety of pediatric disorders and subspecialties at any individual center;by few established, multidisciplinary programs in pediatric PH;and by limited interactions among existing PVD programs. Multi-center investigations are necessary for sufficiently powered interventional studies, but study designs have been restricted by lack of knowledge as to disease phenotypes, clinical course, outcomes, and age-appropriate endpoints. Our objective, therefore, is the establishment and operation of a Bioinformatics Clinical Coordinating Center (BCCC) for advancing the understanding and treatment of PVD in children, comprised of national leaders in pediatric pulmonary and cardiac medicine, informatics, and biostatistics as well as registry-based and electronic health records (EHR) clinical research. We leverage and extend the existing Pediatric Pulmonary Hypertension Network (PPHnet) for large-scale registry and EHR-based research, using a well tested and widely adopted open-source data warehouse technology infrastructure (i2b2/SHRINE), developed through the NIH National Centers for Biocomputing and Clinical and Translational Science Award (CTSA) Programs. The goal of this proposal is three-fold: (1) establish a sustainable, open source, reusable registry infrastructure across 8 PPHnet sites to capture multi-sourced EHR, """"""""traditional"""""""" prospective patient-based data, and patient reported outcomes (PROs) across a large, prospective, pediatric pulmonary hypertension (PH) observational cohort;(2) enroll >500 registry subjects and capture data on >750 EHR subjects across 8 PPHnet sites, linking EHR with registry data at 3 sites;(3) address three classes of unanswered questions crucial for the characterization and management of PH, comparing the information value of registry vs. EHR vs. fused data across registry/EHR/PROs, in the domains of spectrum of PH comorbidities, PH indicators and endpoints of morbidity and mortality, and response to therapies in PH.

Public Health Relevance

Pediatric pulmonary vascular disease (PVD), including pediatric pulmonary hypertension, although relatively rare in childhood, exacts a disproportionately high social and economic burden on the children and their families faced with this illness, as well as society as a whole. Yet, treatment options are limited and despite new drug therapies, survival of patients with severe PVD remains poor. We therefore establish a Bioinformatics Clinical Coordinating Center, comprised of experts and centers in pulmonology, cardiology, and bioinformatics, which will collect data on the largest research population of children with this disease to-date, and analyze both registry and electronic health record data in novel ways so that we may better address the many unanswered questions of PVD in children. (End of Abstract)

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Blaisdell, Carol J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Colorado Denver
Schools of Medicine
United States
Zip Code
Brittain, Evan L; Thennapan, Thennapan; Maron, Bradley A et al. (2018) Update in Pulmonary Vascular Disease 2016 and 2017. Am J Respir Crit Care Med 198:13-23
Liptzin, Deborah R; Abman, Steven H; Giesenhagen, Ann et al. (2018) An Approach to Children with Pulmonary Edema at High Altitude. High Alt Med Biol 19:91-98
Geva, Alon; Gronsbell, Jessica L; Cai, Tianxi et al. (2017) A Computable Phenotype Improves Cohort Ascertainment in a Pediatric Pulmonary Hypertension Registry. J Pediatr 188:224-231.e5
Schäfer, Michal; Ivy, D Dunbar; Abman, Steven H et al. (2017) Apparent Aortic Stiffness in Children With Pulmonary Arterial Hypertension: Existence of Vascular Interdependency? Circ Cardiovasc Imaging 10:
Maron, Bradley A; Abman, Steven H (2017) Translational Advances in the Field of Pulmonary Hypertension. Focusing on Developmental Origins and Disease Inception for the Prevention of Pulmonary Hypertension. Am J Respir Crit Care Med 195:292-301
Ong, Mei-Sing; Mullen, Mary P; Austin, Eric D et al. (2017) Learning a Comorbidity-Driven Taxonomy of Pediatric Pulmonary Hypertension. Circ Res 121:341-353
Abman, Steven H (2016) New guidelines for managing pulmonary hypertension: what the pediatrician needs to know. Curr Opin Pediatr 28:597-606
Burkett, Dale A; Slorach, Cameron; Patel, Sonali S et al. (2016) Impact of Pulmonary Hemodynamics and Ventricular Interdependence on Left Ventricular Diastolic Function in Children With Pulmonary Hypertension. Circ Cardiovasc Imaging 9:
Kim, John S; McSweeney, Julia; Lee, Joanne et al. (2016) Pediatric Cardiac Intensive Care Society 2014 Consensus Statement: Pharmacotherapies in Cardiac Critical Care Pulmonary Hypertension. Pediatr Crit Care Med 17:S89-100
Burkett, Dale A; Slorach, Cameron; Patel, Sonali S et al. (2015) Left Ventricular Myocardial Function in Children With Pulmonary Hypertension: Relation to Right Ventricular Performance and Hemodynamics. Circ Cardiovasc Imaging 8:

Showing the most recent 10 out of 11 publications