Mentoring Research in the Physiology and Consequences of Sleep Disordered Breathing

K24更新的建议将继续：（1）为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追求以病人为导向的职业生涯， 研究睡眠障碍;（2）对睡眠呼吸障碍（SDB）患者进行临床研究 包括阻塞性睡眠呼吸暂停（OSA）和（3）增强她进行以患者为导向的研究的能力 和指导。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）是一种高度流行的疾病，影响15-50%的美国人口。 未经治疗的OSA具有显著的发病率和死亡率，包括心血管和神经认知损害。 多个正在进行的项目将提供指导和病人为导向的研究机会博士。 学员第一个项目将研究参与阻塞性睡眠呼吸暂停高患病率的机制途径， 世界贸易中心（WTC）粉尘暴露受试者。我们最近确定慢性鼻窦炎（CRS）是一种 在这个人群中，OSA的独立危险因素与炎症相关，但不是由于 增加鼻腔阻力。我们将（i）测试上呼吸道感觉器官的损伤是否有助于 （ii）鉴定具有CRS的WTC应答者中的主要OSA表型性状， 将他们与睡眠诊所的阻塞性睡眠呼吸暂停患者进行比较。（U 01 OH 011481）第二个项目（由Fisher & Paykel Healthcare）涉及开发和测试无创通气的新算法， 肥胖低通气综合征患者。这些包括仅在睡眠期间施加压力 (for舒适度）和压力自动滴定以确保功效。合作研究的第三个领域 与Ricardo Osorio，医学博士一起研究了睡眠与阿尔茨海默病（AD）之间的关系。我们将 扩展我们先前在认知正常的老年人中进行的研究， 我们最近证实，OSA与2年内淀粉样蛋白负荷增加的标志物有关， 随访（1 R 01 HL 118624，R 01 AG 056031）。我们将对这些受试者进行另外4年的随访，以测试 慢波睡眠和OSA严重程度对淀粉样蛋白沉积的纵向影响。我们亦会研究 （R 01 AG 056531）睡眠障碍是否在非裔美国人中更常见， 与白人相比，是解释淀粉样蛋白负担增加的因素之一。概述的活动 这些建议是针对Ayappa博士职业发展的。辅导工作将满足以下需要： 睡眠医学的新研究者。实验工作为学员提供学习机会， 与了解OSA的生理学及其结果、诊断和治疗相关， 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.