Pediatric Asthma Disparities: The Role of Sleep and Immune Balance

 描述(由申请者提供)：这份K24申请提出了一个导师计划，以患者为导向，研究儿童哮喘健康差异的多层次贡献者，重点是睡眠和免疫平衡。K24候选人是布朗大学沃伦·阿尔伯特医学院精神病学和人类行为系的副教授(研究)，有资助行为干预和纵向研究的历史，旨在改善城市儿童的哮喘结果，解决儿童哮喘的健康差距。培训计划：候选人将获得哮喘临床免疫学和睡眠生理学方面的额外培训，包括评估与哮喘和睡眠相关的免疫生物标记物的最新方法，以及通过实验方法评估睡眠现象学的实验室方法。研究计划：拟议的研究涉及对实验性睡眠中断对免疫平衡的影响(Th1/Th2细胞因子比率-Th1/Th2R；血浆IL-6-PIL-6)的创新调查，以及与哮喘相关的肺功能(肺活量测定FEV1)和城市持续性哮喘儿童(8-10岁)白天表现的相关变化。40名儿童和他们的主要照顾者每人将参加一个受试者内的方案，有两个实验睡眠条件：基线睡眠(1个过夜，实验室多导睡眠监测(PSG)睡眠研究)，然后是睡眠碎片(1个过夜，实验室PSG)。在每一种情况下，孩子们都会在家中遵循6天的睡眠稳定时间表。我们将每天监测睡眠和肺功能(通过肺活量测定FEV1)，以确认是否符合睡眠标准，并评估哮喘状态。我们包括对免疫生物标记物和每种情况下的白天表现的评估。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记物如何与睡眠中断有关，以及哮喘恶化的临床指标(肺功能)，以识别那些风险最高的人，优先考虑干预目标，并改善治疗反应。指导计划：建议的指导计划为对POR感兴趣的博士后研究员、住院医生和初级教员提供指导机会。受训者将参与正在进行的关于儿童哮喘差异的纵向和干预性研究，包括拟议的研究，该研究将侧重于促进城市儿童哮喘和睡眠的生物过程。非常重视少数群体学员的招聘和遴选。这一总体计划充分利用了布朗医学院为博士后研究员、住院医生和初级教师提供的丰富资源和培训机会，包括几个T32奖学金计划、众多获得K奖和小额赠款的初级教师、致力于培训的多样性、研究设计、伦理学和统计学方面的研讨会，以及成熟的评估基础设施。

 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.