Pediatric Asthma Disparities: The Role of Sleep and Immune Balance

 描述（由申请人提供）：该K24申请提出了一项以患者为导向的研究中的导师计划，该计划涉及儿童哮喘健康差异的多层次贡献者，重点关注睡眠和免疫平衡。K24候选人是布朗大学沃伦·阿尔珀特医学院精神病学和人类行为系的副教授（研究），有行为干预和纵向研究的资助历史，旨在改善城市儿童的哮喘结局，并解决儿童哮喘的健康差异。培训计划：候选人将获得哮喘临床免疫学和睡眠生理学的额外培训，包括评估与哮喘和睡眠相关的免疫生物标志物的最先进方法，以及通过实验方法评估睡眠现象的实验室方法。研究计划：该研究涉及实验性睡眠中断对免疫平衡（Th 1/Th 2细胞因子比率-Th 1/Th 2 R;血浆IL-6 -pIL-6）的影响，以及哮喘相关肺功能（肺量计测定的FEV 1）和持续性哮喘城市儿童（8-10岁）日间表现的相关变化的创新性调查。40名儿童和他们的主要照顾者将各自参加一项受试者内方案，其中有两种实验性睡眠条件：基线睡眠（1次过夜，实验室内多导睡眠图（PSG）睡眠研究），然后是睡眠片段（1次过夜，实验室内PSG）。在每种情况发生之前，儿童将在家中遵循6天的睡眠稳定时间表。我们将每天监测睡眠和肺功能（肺功能测定法FEV 1），以确认是否符合睡眠标准，并评估哮喘状态。我们包括评估免疫生物标志物和每种条件下的日间表现。这项研究的结果最终将支持城市和种族多样化儿童的哮喘和睡眠干预的发展。我们的数据将阐明与哮喘和睡眠相关的免疫生物标志物如何与睡眠中断有关，以及哮喘恶化的临床指标（肺功能），以确定风险最高的患者，优先考虑干预目标，并改善治疗反应。指导计划：拟议的指导计划为博士后研究员、居民和对POR感兴趣的初级教师提供了指导机会。学员将参与正在进行的关于儿童哮喘差异的纵向和干预研究，包括拟议的研究，该研究将重点关注导致城市儿童哮喘和睡眠的生物学过程。特别强调征聘和挑选少数族裔学员。这个整体计划利用丰富的资源和培训机会提供给博士后研究员，居民和初级教师在布朗医学院，包括几个T32奖学金计划，许多初级教师与K奖和小额赠款，致力于培训的多样性，研讨会在研究设计，伦理学和统计学，并建立基础设施进行评估。

 DESCRIPTION (provided by applicant): 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.