Mentoring Research in the Physiology of Sleep Disordered Breathing

描述(由申请人提供)：这项建议将为Ayappa博士提供受保护的时间和支持，同时她(1)指导研究生、博士后研究员和初级教员在以患者为导向的睡眠障碍研究领域寻求职业生涯；(2)对睡眠呼吸障碍(SDB)患者进行临床研究；(3)增强她进行以患者为导向的研究和指导的能力。Ayappa博士积极参与SDB的生理学、诊断、治疗和结果的研究，为指导提供研究机会。阻塞性睡眠呼吸暂停(OSA)是一种非常普遍的疾病，估计影响15%的美国人口。未经治疗的阻塞性睡眠呼吸暂停综合征具有显著的发病率和死亡率，包括心血管和神经认知障碍。提出了研究的多个方向。第一个项目(1U01OH010415-01)利用世界贸易中心应答者鼻部不适和阻塞性睡眠呼吸暂停共存的情况，研究鼻部病理在阻塞性睡眠呼吸暂停的发展过程中的作用及其对CPAP依从性的影响。具体目的是(I)在1000名没有9/11OSA前证据的受试者中检查9/11 OSA后(使用家庭睡眠监测)与上呼吸道疾病的关系；(Ii)确定9/11后OSA、上呼吸道疾病、鼻部炎症(白细胞计数和可溶性IL-8、IL-6、肿瘤坏死因子)和鼻阻力(鼻腔测压)之间的关系；(Iii)OSA患者对CPAP黏附的鼻阻力，以表明使用CPAPFlex降低呼气压力将改善CPAP依从性。第二个项目(候选人先前的R01,2013年2月更新版本)的目标是了解阻塞性睡眠呼吸暂停综合征患者SDB和日间功能之间的关系(或缺乏这种关系的原因)。尽管大多数阻塞性睡眠呼吸暂停综合征患者报告日间过度嗜睡(EDS)，但SDB和嗜睡的测量之间的相关性很差。越来越清楚的是，个体易感性等因素可能会导致个体患者对SDB压力的反应方式不同。其具体目的是证明受控次优CPAP(标准剂量的SDB)后出现的EDS水平与睡眠剥夺24小时后的EDS水平之间的相关性。这个假设是，对这两种不同形式的睡眠干扰的易感性是相关的，并定义了一个人的一种“特征”。这项工作的延伸是第三个合作项目(目前得到资助的试点项目)，该项目在一组老年受试者中检查SDB和阿尔茨海默病(AD)生物标记物之间的关系。这项研究考察了AD是否会导致老年人的SDB，或者SDB是否会作为促进神经退化的因素。提案中概述的活动对科学和公共卫生都有影响。指导工作将解决国家睡眠障碍中心记录的睡眠障碍研究人员严重短缺的问题。这项实验工作对于了解SDB的生理学及其结果、其诊断和治疗具有改善数百万睡眠呼吸暂停患者健康和生活质量的潜力具有重要意义。

DESCRIPTION (provided by applicant): This proposal will provide protected time and support to Dr. Ayappa while she (1) mentors graduate students, post-doctoral fellows and junior faculty pursuing careers in patient-oriented research in sleep disorders; (2) conducts clinical research in patients with sleep disordered breathing (SDB) and (3) augments her capabilities to conduct patient-oriented research and mentoring. Dr. Ayappa is actively involved in research in physiology, diagnosis, treatment and outcomes of SDB that provides research opportunities for mentoring. Obstructive sleep apnea (OSA) is a highly prevalent disorder estimated to affect 15% of the US population. Untreated OSA has significant morbidity and mortality including cardiovascular and neurocognitive impairment. Multiple directions are proposed for the research. The first project (1U01OH010415-01) uses the coexistence of the high prevalence of nasal complaints and OSA in World Trade Center responders to examine the role of nasal pathology in the development of OSA and its impact on CPAP adherence. The Specific aims are to (i) Examine the relationships between post-9/11 OSA (using home sleep monitoring) and upper airway disease, in 1000 subjects without evidence of pre-9/11OSA (ii) Determine the relationship between post-9/11 OSA, upper airway disease, nasal inflammation (leukocyte counts and soluble IL-8, IL-6, TNF¿) and nasal resistance (rhinomanometry) (iii) Relate nasal resistance to CPAP adherence in patients with OSA to show that reduction of expiratory pressure using CPAPFlex will improve CPAP adherence. The goal of the second project (candidate's prior R01with renewal revision Feb 2013) is to understand the relationship (or reasons for lack thereof) between SDB and daytime function in OSA patients. Although majority of patients with OSA report excessive daytime sleepiness (EDS), the correlation between measures of SDB and sleepiness is poor. It is increasingly clear that factors such as individual susceptibility may contribute to differences in how individual patients respond to the stress of SDB. The specific aim is to demonstrate a correlation between the level of EDS that develops after controlled suboptimal CPAP (a standardized dose of SDB) and the level of EDS after 24 hours of sleep deprivation. The hypothesis is that susceptibility to these two different forms of sleep disruption is correlated and defines a "trait" for an individual. An extension of this work i a third collaborative project (currently funded pilots) that examines the relationship between SDB and Alzheimer's Disease (AD) biomarkers in a cohort of elderly subjects. The study examines whether AD causes SDB in the elderly, or if SDB acts as a factor promoting neurodegeneration. The activities outlined in the proposal have implications for science and public health. The mentoring work will address a critical shortage of researchers in sleep disorders as documented by the National Center on Sleep Disorders. The experimental work is relevant for understanding the physiology of SDB and its outcomes, its diagnosis and treatment with potential for improving health and quality of life in millions of patients who suffer from sleep apnea.