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（由适用提供）：该提案将为Ayappa博士提供受保护的时间和支持，而她（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的职业； （2）对呼吸失调的患者进行临床研究（SDB），（3）增强了她进行以患者为导向的研究和心理研究的能力。 Ayappa博士积极参与SDB的生理学，诊断，治疗和结果研究，这些研究提供了心理研究机会。阻塞性睡眠呼吸暂停（OSA）是一种高度普遍的疾病，估计会影响美国人群的15％。未经治疗的OSA具有明显的发病率和死亡率，包括心血管和神经认知障碍。提出了多个方向进行研究。第一个项目（1U01OH010415-01）使用鼻诉和OSA在世界贸易中心响应者中的高流行率，以检查鼻病理学在OSA发展中的作用及其对CPAP依从性的影响。具体目的是（i）检查9/11后OSA（使用家庭睡眠监测）和上空气道疾病之间的关系，在1000名受试者中，没有证据前9/11 OSA（ii）确定9/11 OSA，后9/11 OSA，上空气道疾病，上呼吸道疾病，鼻腔感染（Leukocyte）和固体IL-8，IL-8，IL-6，iil-6，iil-6，iil-6，tnaf ry）（）（iil-l-6，iil）（iil）（iil）（iil）（iil）（NASAS）（NASAS）（NASAS）（NASAS）（NASI）（NASI）（NASIN）（NASAS）（）（）（）（） OSA患者对CPAP依从性的鼻阻力表明，使用CPAPFLEX降低到期压力将提高CPAP依从性。第二个项目的目标（候选人的先前R01与2013年2月的续签修订）是要了解OSA患者SDB与白天功能之间的关系（或缺乏其原因）。尽管大多数OSA患者报告了白天嗜睡过多（EDS），但SDB的度量与嗜睡量之间的相关性很差。越来越明显的是，诸如个体易感性之类的因素可能导致单个患者对SDB压力的反应方式的差异。具体的目的是证明在受控次优的CPAP（标准剂量的SDB）和24小时后睡眠剥夺后发展后的ED水平之间的相关性。假设是，对这两种不同形式的睡眠破坏的敏感性与个人定义了“特征”。这项工作的扩展是我第三个合作项目（目前由资助的钢琴），研究了SDB与阿尔茨海默氏病（AD）生物标志物之间的关系。该研究检查AD是否会导致SDB在较早的情况下，还是SDB是促进神经变性的因素。该提案中概述的活动对科学和公共卫生有影响。心理工作将解决由国家睡眠障碍中心记录的睡眠障碍研究人员的严重短缺。实验工作与了解SDB及其结果的生理学，其诊断和治疗具有改善患有睡眠呼吸暂停的数百万患者的健康和生活质量的治疗相关。