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: 8703762
• 负责人: INDU A AYAPPA
• 金额: $ 9.33万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 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 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8703762
• 关键词: Address; Adherence; Adult; Affect; Alzheimer' s Disease; Alzheimer' s disease risk; Area; Biological Markers; Brain; Cardiovascular system; Chronic; Clinical Research; Collaborations; Continuous Positive Airway Pressure; Crossover Design; Development; Diagnosis; Disease; Dissociation; Dose; Double-Blind Method; Dust; Elderly; Excessive Daytime Sleepiness; Excision; Experimental Models; Faculty; Funding; Goals; Grant; Health; High Prevalence; Home environment; Hour; Human; IL8 gene; Impairment; Individual; Inflammation; Interleukin-6; Measures; Mentors; Metric; Modality; Modeling; Morbidity - disease rate; Nerve Degeneration; Neurocognitive; 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; Research; Research Infrastructure; Research Personnel; Resistance; Rhinomanometry; Role; Science; Severities; Sinusitis; Sleep; Sleep Apnea Syndromes; Sleep Deprivation; Sleep Disorders; Snoring; Stress; Symptoms; TNF gene; Testing; Time; Treatment outcome; White Blood Cell Count procedure; Wood material; Work; World Trade Center disaster; base; career; cohort; experience; expiration; graduate student; improved; indexing; medical schools; mortality; novel; patient oriented; patient oriented research; pressure; programs; public health relevance; response; skills; 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）对睡眠呼吸障碍（SDB）患者进行临床研究;（3）增强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，治疗和结果的研究，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，估计影响15%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。提出了多个研究方向。第一个项目（1U 01 OH 010415 -01）使用鼻投诉和OSA在世界贸易中心应答者中的高患病率共存，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。具体目标是：（一）审查9/11后OSA与（ii）确定9/11后OSA、上呼吸道疾病、鼻腔炎症之间的关系（白细胞计数和可溶性IL-8、IL-6、TNF-α）和鼻阻力（气道测压）（iii）将OSA患者的鼻阻力与CPAP依从性相关联，以表明使用CPAPFlex降低呼气压将改善CPAP依从性。第二个项目（候选人之前的R 01，更新版本为2013年2月）的目标是了解SDB与OSA患者日间功能之间的关系（或缺乏相关性的原因）。虽然大多数OSA患者报告白天过度嗜睡（EDS），但SDB和嗜睡之间的相关性很差。越来越清楚的是，个体易感性等因素可能导致个体患者对SDB应激反应的差异。具体目的是证明受控次优CPAP（标准化剂量的SDB）后出现的EDS水平与睡眠剥夺24小时后EDS水平之间的相关性。该假说认为，对这两种不同形式的睡眠中断的易感性是相关的，并定义了一个人的“特质”。这项工作的延伸是第三个合作项目（目前资助的试点），该项目在老年受试者队列中检查SDB和阿尔茨海默病（AD）生物标志物之间的关系。该研究探讨了AD是否导致老年人的SDB，或者SDB是否作为促进神经退行性变的因素。提案中概述的活动对科学和公共卫生具有影响。指导工作将解决睡眠障碍研究人员的严重短缺，如国家睡眠障碍中心所记录的那样。实验工作对于了解SDB的生理学及其结果，其诊断和治疗具有改善数百万患有睡眠呼吸暂停的患者的健康和生活质量的潜力。