Thursday, April 3, 2025
4/3/2025
Therapeutic Strategies for the Management of Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension - SUMMARY This proposed Mentored Patient-Oriented Research Career Development Award (K23) will provide Samuel Gentle, MD, with the mentorship, training, and research experience needed in his transition towards an independent clinician scientist and leader in the field of bronchopulmonary associated pulmonary hypertension (BPD-PH). Over the course of his career, Dr. Gentle aims to reduce morbidity and mortality in children with BPD-PH, a disease in which 50% of children die by 2 years of age and nearly half of survivors have continuation of disease into adulthood. This commitment therefore directly aligns with the mission of the National Heart, Lung, and Blood Institute to prevent and treat heart and lung disorders so that individuals live longer and more fulfilling lives. Dr. Gentle will accomplish this career goal through novel translational and interventional investigations and future multi-center clinical trials of therapeutic strategies that reduce adverse outcomes in infants with BPD-PH. In order to further facilitate these accomplishments, Dr. Gentle's complimentary and comprehensive mentorship and advisory team provides a group of investigators with a rich history of NIH funded investigations and prior mentorship; formal training inclusive of a (1) Master of Science in Public Health in Biostatistics, (2) completion of a graduate certificate in Medical Signal and Image Analysis, and (3) echocardiographic assessment of BPD-PH; and a research strategy that is an intentional extension of his ongoing research in infants with BPD-PH. Dr. Gentle has recently produced multiple high impact publications in AJRCCM including an investigation of intermittent hypoxemia characteristics related to BPD-PH thereby providing a surrogate metric to evaluate therapeutic responses to BPD-PH interventions including those in the current proposal's SA2 and SA3. These characteristics, in addition to demographic and clinical characteristics detailed in Dr. Gentle's additional publication in AJRCCM, provide the framework for BPD-PH risk estimation as detailed in SA1. In summary, the current proposal addresses the minimal evidence for (1) prediction of BPD-PH in extremely preterm infants (SA1), (2) characterizing subphenotypes of infants with BPD-PH using group trajectory modeling (SA2), and (3) oxygen saturation targets that reduce echocardiographic BPD-PH by performing a randomized, crossover trial in infants with established BPD-PH randomized to oxygen saturations of 92-95% and 95-98% (SA3). Insights from these investigations will strengthen the currently expert consensus-based recommendations from the American Thoracic Society and American Heart Association in the optimal oxygen saturation targets and pulmonary hypertension specific pharmacotherapies used to treat children with BP-PH. Subsequent R01 funded multi-center clinical trials will provide consequential evidence that will influence standards of care in children with this disease.
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