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Principal Investigator: Samuel J Gentle
Organization: UNIVERSITY OF ALABAMA AT BIRMINGHAM
Fiscal Year: 2024
Award: $10,000
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
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.
Terms: <0-11 years old><2 year old><2 years of age><21+ years old><Address><Adult><Adult Human><Advisory Committees><Age><American><American Heart Association><Animal Model><Animal Models and Related Studies><Award><Biometrics><Biometry><Biostatistics><Bronchopulmonary Dysplasia><Cardiac Diseases><Cardiac Disorders><Cardiovascular><Cardiovascular Body System><Cardiovascular Organ System><Cardiovascular system><Caring><Cell Communication and Signaling><Cell Signaling><Characteristics><Chest><Child><Child Care><Child Youth><Children (0-21)><Chronic lung disease><Classification><Clinical><Consensus><Cross-Over Studies><Cross-Over Trials><Crossover Studies><Crossover Trials><Data><Data Analyses><Data Analysis><Development><Disease><Disorder><Doctor of Philosophy><Drug Therapy><Early Diagnosis><Early identification><Echocardiogram><Echocardiography><Expectancy><Exposure to><Frequencies><Funding><Future><Goals><Guidelines><Health Care Costs><Health Costs><Healthcare Costs><Heart Diseases><Heart Vascular><History><Hypoxemia><Image Analyses><Image Analysis><Individual><Infant><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Investigation><Investigators><K23 Award><K23 Mechanism><K23 Program><Knowledge><Lead><Lung><Lung Diseases><Lung Respiratory System><Master of Science><Master's Degree><Medical><Mentored Patient-Oriented Research Career Development Award><Mentored Patient-Oriented Research Career Development Award (K23)><Mentorship><Mission><Modeling><Morbidity><Morbidity - disease rate><Multi-Institutional Clinical Trial><Multi-center clinical trial><Multi-site clinical trial><Multicenter clinical trial><Multisite clinical trial><NHLBI><NIH><National Heart, Lung, and Blood Institute><National Institutes of Health><O element><O2 element><Outcome><Oxygen><Oxygen Inhalation Therapy><Oxygen Therapy Care><Patients><Pb element><Ph.D.><PhD><Pharmacotherapy><Physicians><Pre-Clinical Model><Precision therapeutics><Preclinical Models><Premature Infant><Prevention><Probability><Public Health><Publications><Puericulture><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Hypertension><Randomization trial><Randomized><Recommendation><Recording of previous events><Reporting><Research><Research Design><Research Personnel><Researchers><Retinopathy of Prematurity><Retrolental Fibroplasia><Risk><Risk Estimate><Role><Scientific Publication><Scientist><Signal Transduction><Signal Transduction Systems><Signaling><Societies><Study Type><Survivors><Systematics><Task Forces><Therapeutic><Thorace><Thoracic><Thorax><Time><Training><Transthoracic Echocardiography><United States National Institutes of Health><Vasodilating Agent><Vasodilator Agents><Vasodilator Drugs><Vasodilators><Vulnerable Populations><Warburg Therapy><adulthood><adverse consequence><adverse outcome><advisory team><age 2 years><aged 2 years><aged two years><ages><biological signal transduction><career><chronic lung disease in infants><chronic lung disease in neonatal infants><chronic lung disease in neonates><chronic lung disease in newborns><chronic lung disease in prematurity><chronic lung disease in preterm infants><chronic lung disease of infancy><chronic lung disease of prematurity><chronic pulmonary disease><circulatory system><data interpretation><death risk><design><designing><developmental><disease of the lung><disorder of the lung><drug treatment><early detection><evidence base><experience><extreme prematurity><extremely premature infant><extremely preterm><extremely preterm infant><heart disorder><heart sonography><heavy metal Pb><heavy metal lead><high risk><histories><hypoxemic><iNO><image evaluation><image interpretation><improved><improved outcome><infant chronic lung disease><infants born premature><infants born prematurely><infants with chronic lung disease><inhaled nitric oxide><innovate><innovation><innovative><insight><interventional strategy><kids><lung disorder><model development><model developments><model of animal><mortality><mortality risk><neonatal chronic lung disease><newborn chronic lung disease><novel><oxygen administration><oxygen therapy><patient subclass><patient subcluster><patient subgroups><patient subpopulations><patient subsets><patient subtypes><post-prematurity respiratory disease><precision therapies><precision treatment><premature baby><premature infant human><premature retinopathy><preterm baby><preterm infant><preterm infant human><preterm infants with chronic lung disease><prevent><preventing><prospective><pulmonary><randomisation><randomization><randomized trial><randomly assigned><response to therapy><response to treatment><screening><screenings><sildenafil><social role><study design><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><therapeutic response><therapy response><tool><treatment response><treatment responsiveness><two year old><two years of age><very premature><very preterm><vulnerable group><vulnerable individual><vulnerable people><youngster>