Mentoring Research in the Physiology and Consequences of Sleep Disordered Breathing

睡眠呼吸障碍的生理学和后果的指导研究

基本信息

批准号：
9751019
负责人：
INDU A AYAPPA
金额：
$ 10.33万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751019
关键词：
Address Adult Affect African African American Age Alcohol consumption Algorithms Alzheimer disease prevention Alzheimer&apos s Disease Amyloid Amyloid deposition Anatomy Area Arousal Brain Breathing Cardiovascular system Cerebrospinal Fluid Chronic Clinic Clinical Research Cognition Cognitive Collaborations Continuous Positive Airway Pressure Data Set Development Diagnosis Discrimination Disease Dust Elderly Enrollment Ensure Environmental air flow Evaluation Excision Exposure to Faculty Fibrosis Functional disorder Funding Gastroesophageal reflux disease Gender Goals Grant Health Healthcare High Prevalence Home environment Hypercapnia Hypercapnic respiratory failure IL8 gene Impairment Individual Inflammation Infrastructure Interleukin-6 Intervention Knowledge Learning Literature Longitudinal cohort Measures Medicine Memory Mentors Modification Morbidity - disease rate Neurocognitive Deficit Neuropathy Nose Obesity Obstructive Sleep Apnea Outcome Pathway interactions Patients Pattern Phenotype Physiology Pickwickian Syndrome Polysomnography Population Positron-Emission Tomography Postdoctoral Fellow Quality of life Race Recovery Research Research Personnel Resistance Respiratory Failure Risk Risk Factors Role Sensory Severities Sleep Sleep Apnea Syndromes Sleep Disorders Sleep disturbances Slow-Wave Sleep Spinal Puncture Testing Time Titrations Treatment outcome Ventilator Wakefulness Work World Trade Center disaster active method career career development chronic rhinosinusitis cohort follow-up graduate student improved mortality neuromuscular new therapeutic target novel patient oriented research pressure public health relevance respiratory skills sleep quality trait uptake vibration

项目摘要

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.

这项 K24 续订提案将继续：(1) 为 Ayappa 博士提供受保护的时间和支持，同时她指导研究生、博士后研究员和初级教师从事以患者为导向的职业生涯睡眠障碍研究；（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中心的研究的能力和指导。 Ayappa 博士积极参与病理生理学、诊断、治疗和治疗方面的研究 SDB 的成果为指导提供了研究机会。阻塞性睡眠呼吸暂停 (OSA) 是一种非常普遍的疾病，影响着 15-50% 的美国人口。未经治疗的 OSA 具有显着的发病率和死亡率，包括心血管和神经认知障碍。多个正在进行的项目将为 Ayappa 博士的团队提供指导和以患者为导向的研究机会学员。第一个项目将研究 OSA 高患病率所涉及的机制途径世界贸易中心 (WTC) 粉尘暴露对象。我们最近将慢性鼻窦炎 (CRS) 确定为该人群中 OSA 的独立危险因素与炎症相关，但并非由于鼻阻力增加。我们将 (i) 测试上呼吸道感觉器官的损伤是否会导致患有 CRS 的 WTC 应答者中的 OSA，并且 (ii) 确定 WTC 应答者中主要的 OSA 表型特征，以及将他们与睡眠诊所的 OSA 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气的新型算法肥胖低通气综合征患者。其中包括仅在睡眠期间施加压力（为了舒适）和自动滴定压力以确保功效。第三个合作研究领域与医学博士 Ricardo Osorio 一起研究睡眠与阿尔茨海默病 (AD) 之间的关系。我们将扩展我们之前对认知正常老年人的纵向队列的研究，其中我们最近证明 OSA 与 2 年内淀粉样蛋白负荷增加的标志物相关后续（1R01HL118624、R01AG056031）。我们将再跟踪这些主题 4 年以测试慢波睡眠和 OSA 严重程度对淀粉样蛋白沉积的纵向影响。我们还将检查 (R01AG056531) 睡眠障碍是否在非裔美国人中更为常见与白人相比，这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阿亚帕博士的职业发展。指导工作将满足需要适合睡眠医学的新研究人员。实验工作为学员和学员提供了学习机会对于了解 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。