Mentoring Research in the Physiology of Sleep Disordered Breathing

睡眠呼吸障碍生理学的指导研究

• 批准号: 9319784
• 负责人: INDU A AYAPPA
• 金额: $ 9.33万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9319784
• 关键词: Address; Adherence; Adult; Affect; Alzheimer' s Disease; Alzheimer' s disease risk; Area; Biological Markers; Cardiovascular system; Chronic; Clinical Research; Collaborations; Continuous Positive Airway Pressure; Crossover Design; Development; Diagnosis; Disease; Dissociation; Dose; Double-Blind Method; Drowsiness; Dust; Elderly; Excessive Daytime Sleepiness; Excision; Experimental Models; Faculty; Funding; Goals; Grant; Health; High Prevalence; Home environment; Hour; Human; IL8 gene; Individual; Inflammation; Interleukin-6; Measures; Mentors; Modality; Modeling; Morbidity - disease rate; Nerve Degeneration; Neurocognitive Deficit; Nose; Obesity; Obstruction; Obstructive Sleep Apnea; Outcome; Pathology; Patients; Phenotype; Physiology; Polysomnography; Population; Postdoctoral Fellow; Predisposition; Public Health; Quality of life; Questionnaires; Randomized; Recovery; Reporting; Reproducibility; Research; Research Infrastructure; Research Personnel; Resistance; Rhinomanometry; Role; Science; Severities; Sleep; Sleep Apnea Syndromes; Sleep Deprivation; Sleep Disorders; Snoring; Standardization; Stress; Symptoms; TNF gene; Testing; Time; Treatment outcome; White Blood Cell Count procedure; Wood material; Work; World Trade Center disaster; base; brain health; career; chronic rhinosinusitis; cohort; experience; expiration; graduate student; improved; indexing; individual patient; medical schools; mortality; novel; patient oriented; patient oriented research; persistent symptom; pressure; programs; public health relevance; response; skills; sleep regulation; therapy adherence; trait; vigilance

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.

描述（由申请人提供）：该提案将为 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师从事以患者为导向的睡眠障碍研究；(2) 开展睡眠障碍研究； (3) 睡眠呼吸障碍 (SDB) 患者的临床研究增强了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、治疗和结果研究，为以下患者提供研究机会。阻塞性睡眠呼吸暂停 (OSA) 是一种非常普遍的疾病，估计会影响 15% 的美国人口。该疾病的发病率和死亡率很高，包括心血管和神经认知障碍。第一个项目 (1U01OH010415-01) ）利用世贸中心应答者中鼻部不适和 OSA 的高患病率并存来研究鼻部病理学在 OSA 发展中的作用及其对具体目标是 (i) 在 1000 名没有 9/11 之前 OSA 证据的受试者中检查 9/11 后 OSA（使用家庭睡眠监测）与上呼吸道疾病之间的关系 (ii) 确定两者之间的关系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、TNF�）和鼻阻力（鼻测压） (iii) 与鼻阻力相关评估 OSA 患者的 CPAP 依从性，以表明使用 CPAPFlex 降低呼气压力将提高 CPAP 依从性。第二个项目（候选者之前的 R01，2013 年 2 月更新修订）是了解 SDB 之间的关系（或缺乏这种关系的原因）。尽管大多数 OSA 患者报告白天过度嗜睡 (EDS)，但 SDB 测量值与嗜睡之间的相关性越来越明显。例如，个体易感性可能会导致个体患者对 SDB 压力的反应存在差异。具体目的是证明受控次优 CPAP（标准化剂量的 SDB）后出现的 EDS 水平与 EDS 水平之间的相关性。假设是，对这两种不同形式的睡眠中断的敏感性是相关的，并定义了个体的“特征”。这项工作的延伸是第三个合作项目（目前已获得资助）。该研究检查了一组老年受试者中的 SDB 和阿尔茨海默氏病 (AD) 生物标志物之间的关系。根据国家睡眠障碍中心的记录，指导工作将解决睡眠障碍研究人员的严重短缺问题，该实验工作有助于了解 SDB 的生理学及其结果、诊断和治疗。改进的潜力数百万睡眠呼吸暂停患者的健康和生活质量。