Mentoring Research in the Physiology and Consequences of Sleep Disordered Breathing

K24续展的这一提议将继续：(1)向Ayappa博士提供受保护的时间和支持 她指导研究生、博士后研究员和初级教师在以患者为导向的职业生涯中 睡眠障碍的研究；(2)睡眠障碍呼吸患者的临床研究 包括阻塞性睡眠呼吸暂停(OSA)和(3)增强了她进行以患者为导向的研究的能力 和辅导。Ayappa博士积极参与病理生理学、诊断、治疗和 SDB的成果，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，影响着美国15%-50%的人口。 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。 多个正在进行的项目将为阿亚帕博士的指导和以患者为导向的研究提供机会 指导者。第一个项目将研究阻塞性睡眠呼吸暂停综合征高患病率的机制途径。 世界贸易中心(WTC)粉尘暴露对象。我们最近发现慢性鼻窦炎(CRS)是一种 该人群中OSA的独立危险因素与炎症有关，但与 鼻腔阻力增加。我们将(I)测试上呼吸道感觉器的损伤是否有助于 有CRS的WTC应答者的OSA和(Ii)确定WTC应答者的主要OSA表型特征和 将他们与睡眠诊所的阻塞性睡眠呼吸暂停综合症患者进行比较。(U01OH011481)第二个项目(由Fisher& Paykel Healthcare)涉及开发和测试用于无创通风的新算法 肥胖、低通气量综合征患者。这些措施包括仅在睡眠期间施加压力。 (为了舒适)和自动压力滴定，以确保疗效。合作研究的第三个领域 医学博士里卡多·奥索里奥研究了睡眠与阿尔茨海默病(AD)之间的关系。我们会 将我们之前的工作扩展到我们特征良好的认知正常老年人纵向队列中 我们最近证实，OSA与两年内淀粉样蛋白负荷增加的标志物有关 随访(1R01HL118624，R01AG056031)。我们将再跟踪这些受试者4年，以测试 慢波睡眠和阻塞性睡眠呼吸暂停严重程度对淀粉样蛋白沉积的纵向影响。我们还将检查 (R01AG056531)睡眠障碍，这在非洲裔美国人中更常见 与白人相比，是解释淀粉样蛋白负担增加的因素之一。中概述的活动 该提案针对的是阿亚帕博士的职业发展。指导工作将满足以下需求 给睡眠医学的新研究人员。实验工作为学员提供了学习机会，并 对于了解阻塞性睡眠呼吸暂停的生理学和转归、诊断和治疗具有重要意义 改善数百万睡眠呼吸暂停患者的健康和生活质量的潜力。

This proposal for a K24 renewal will continue to : (1) provide protected time and support to Dr. Ayappa while she mentors graduate students, post-doctoral fellows and junior faculty pursuing careers in patient-oriented research of sleep disorders; (2) conduct clinical research in patients with sleep disordered breathing (SDB) including obstructive sleep apnea (OSA) and (3) augment her capabilities to conduct patient-oriented research and mentoring. Dr Ayappa is actively involved in research in pathophysiology, diagnosis, treatment and outcomes of SDB that provides research opportunities for mentoring. Obstructive sleep apnea (OSA) is a highly prevalent disorder affecting 15-50% of the US population. Untreated OSA has significant morbidity and mortality including cardiovascular and neurocognitive impairment. Multiple ongoing projects will provide mentoring and patient oriented research opportunities for Dr. Ayappa's mentees. The first project will examine the mechanistic pathways involved in the high prevalence of OSA in World Trade Center (WTC) dust exposed subjects. We recently identified chronic rhinosinistis (CRS) as an independent risk factor for OSA in this population that was associated with inflammation, but was not due to increased nasal resistance. We will (i) test if damage to the upper airway sensory apparatus contributes to OSA in WTC responders with CRS and (ii) identify predominant OSA phenotypic traits in WTC responders and compare them to OSA patients from a sleep clinic. (U01OH011481) The second project (funded by Fisher & Paykel Healthcare) involves development and testing of novel algorithms for non-invasive ventilation in patients with obesity hypoventilation syndrome. These include application of pressures exclusively during sleep (for comfort) and automatic titration of pressures to ensure efficacy. The third area of research in collaboration with Ricardo Osorio, MD examines the relationship between sleep and Alzheimer's Disease (AD). We will extend our prior work in our well characterized longitudinal cohort of cognitively normal older adults in whom we recently demonstrated that OSAwas associated with markers of increased amyloid burden over a 2 year follow-up (1R01HL118624, R01AG056031). We will follow these subjects for an additional 4 years to test the longitudinal effects of slow wave sleep and OSA severity on amyloid deposition. We will also examine (R01AG056531) whether sleep disturbances, which are more common among African-Americans when compared to whites, are one of the factors that explain increases in amyloid burden. The activities outlined in the proposal are directed toward Dr Ayappa's career development. The mentoring work will address the need for new researchers in sleep medicine. The experimental work provides learning opportunities for mentees and is relevant for understanding the physiology of OSA 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.