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.