This K24 application proposes a mentorship program in patient-oriented research in multi-level contributors to pediatric asthma health disparities, wih a focus on sleep and immune balance. The K24 Candidate is an Associate Professor (Research) in the Department of Psychiatry and Human Behavior of the Warren Alpert Medical School at Brown University, with a history of funding in behavioral interventions and longitudinal research aimed at improving asthma outcomes in urban children and addressing health disparities in pediatric asthma. Training Plan: The candidate will obtain additional training in asthma clinical immunology and sleep physiology, including state-of the art methods to assess immune biomarkers relevant to asthma and sleep, and in-lab methods to assess sleep phenomenology through experimental approaches. Research Plan: The research proposed involves an innovative investigation of the effects of experimental sleep disruption on immune balance (Th1/Th2 cytokine ratio-Th1/Th2R; plasma IL-6 -pIL-6), and associated changes in asthma- related lung function (FEV1 by spirometry) and daytime performance in urban children with persistent asthma (8-10 years old). Forty children and their primary caregiver will each participate in a within-subjects protocol, with two experimental sleep conditions: baseline sleep (1 overnight, in-lab polysomnographic (PSG) sleep study), followed by sleep fragmentation (1 overnight, in-lab PSG). Prior to each condition, children will follow a 6-day sleep stabilization schedule at home. We will monitor sleep and lung function (FEV1 by spirometry) daily to confirm eligibility and adherence to sleep criteria, and assess asthma status. We include assessments of immune biomarkers and daytime performance following each condition. Results from this study ultimately will support the development of asthma and sleep interventions for urban and ethnically diverse children. Our data will elucidate how immune biomarkers relevant to asthma and sleep operate in relation to sleep disruption, and clinical indicators of worsening asthma (lung function), to identify those most at risk, prioritize intervention targets, and improve treatment response. Mentoring Plan: The proposed mentoring plan offers opportunities for mentorship of postdoctoral fellows, residents and junior faculty with interests in POR. Mentees will be involved in ongoing longitudinal and intervention studies on pediatric asthma disparities, including the proposed research, which will focus on biological-based processes that contribute to asthma and sleep in urban children. A strong emphasis is placed on the recruitment and selection of minority mentees. This overall plan capitalizes on the rich resources and training opportunities available to postdoctoral fellows, residents and junior faculty at Brown Medical School, including several T32 fellowship programs, numerous junior faculty with K awards and small grants, a commitment to diversity in training, seminars in research design, ethics, and statistics, and an established infrastructure for evaluation.
Pediatric health disparities in the area of asthma and sleep continue to exist. Urban poverty and poorly controlled asthma can both adversely impact sleep quality by disrupting the continuity of nighttime sleep. Increased asthma symptoms and sleep disruption have each been linked with changes in immune balance. The immune imbalance associated with asthma in children may be greater in the context of sleep disruption, and this may adversely impact daytime functioning and increase inflammation that can bring on asthma symptoms. This K24 application will provide mentorship in patient-oriented research to post-doctoral fellows, residents, and junior faculty interested in multi-level contributing factors to disparities in pediatric asthma. The research proposed involves the implementation of an experimental approach to examine the effects of sleep disruption on immune imbalance, asthma-related lung function, and daytime performance in urban children (ages 8-10) with persistent, allergic asthma. Results from this study ultimately will support the development of asthma and sleep interventions for urban and ethnically diverse children. Our data will elucidate how immune biomarkers relevant to asthma and sleep operate in relation to sleep disruption, and clinical indicators of worsening asthma (lung function), to identify those most at risk, prioritize intervention targets, and improve treatment response. Mentorship goals involve providing training to post-doctoral fellows, residents and junior faculty, particularly those from minority backgrounds, in patient-oriented research focused on pediatric health disparities. The proposed career training activities to enhance knowledge and assessment of asthma clinical immunology and sleep physiology, will allow for more broadened opportunities for mentorship to trainees. In addition to the proposed research, mentees will be provided with multiple, ongoing opportunities for training in patient-oriented research on pediatric asthma health disparities.
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