Mechanisms of obstructive sleep apnea syndrome in infants with micrognathia

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PROJECT SUMMARY/ABSTRACT I am a pediatric pulmonologist with fellowship training in sleep medicine and a background in clinical and translational research in pediatric obstructive sleep apnea syndrome (OSAS). My research is focused on the pathophysiology, consequences, and treatment of OSAS in children with craniofacial conditions. The proposed project seeks to determine the mechanisms of OSAS in infants with micrognathia, a group of children with mandibular hypoplasia. OSAS is common in children and is associated with growth failure and a variety of cognitive and cardiovascular sequelae. Infants with micrognathia are one of the highest-risk groups for OSAS, but the mechanisms of OSAS in this population, the effect of OSAS on growth, and the variability in outcomes after surgical intervention for OSAS are poorly understood. In Aim 1, we will assess the structural contributions to OSAS in infants with micrognathia using upper airway MRI and the neuromotor contributions to OSAS by evaluating dynamic pressure-flow relationships. Aim 2 will use a variety of growth assessments, including resting energy expenditure assessment and dual-energy x-ray absorptiometry, to evaluate the causes of poor growth. Aim 3 will determine the impact of surgical treatment for OSAS on the craniofacial structure, neuromotor function, and growth in infants with micrognathia. My long-term goal is to become an independent clinical/translation physician-scientist with unique expertise in the evaluation and management of OSAS in children with craniofacial conditions. The proposed career development award facilitates this career goal by allowing me to obtain further training and experience in imaging data analysis and growth assessment. This is complemented with coursework in biostatistics and clinical study design and management in the outstanding research environment of Children’s Hospital of Philadelphia and the University of Pennsylvania. I have assembled an exceptional multidisciplinary mentorship team. My primary mentor, Dr. Carole Marcus, is an internationally-recognized clinical researcher in pediatric OSAS with an outstanding record of mentorship. My co-mentor, Dr. Richard Schwab, is a pioneer in upper airway imaging in OSAS. These mentors, along with a multidisciplinary Advisory Committee that includes investigators in radiology, plastic surgery, nutrition, and biostatistics, will help guide my career development and will provide content expertise to ensure success of the proposed research. The proposed project, along with the structured mentoring, coursework, and training that comprise the my career development plan, will provide me with the skill and experience necessary to ensure his success as an independent investigator with a unique skill set in better understanding the evaluation and treatment of OSAS in children with micrognathia and other craniofacial conditions.