MECHANISMS OF DIFFERENTIAL SLEEPINESS IN SLEEP APNEA

睡眠呼吸暂停中不同睡眠的机制

• 批准号: 6716888
• 负责人: TERRI Elizabeth WEAVER
• 金额: $ 37.98万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6716888
• 关键词: actigraphy; adipose tissue; body composition; cardiovascular disorder; circadian rhythms; clinical research; comorbidity; depression; drug /agent; epidemiology; homeostasis; human middle age (35-64); human subject; obesity; pain; personal log /diary; polysomnography; sleep; sleep apnea; wakefulness

The purpose of this proposal is to explore potential operating mechanisms in the differential sleepiness observed in patients with equivalent degrees of obstructive sleep apnea (OSA). Within a given level of disease severity, i.e., number of respiratory disturbances during sleep, inter-individual differences, or differential vulnerability to sleepiness, have been noted in both subjectively measured and objectively measured daytime sleepiness. The reason for this phenomenon remains unclear. Critical to the management of patients with OSA is the understanding of mechanisms associated with the development of daytime sleepiness. We hypothesize that the variance in daytime sleepiness (EDS)will have a substantial trait component in addition to state-related factors among patients with equivalent levels of OSA severity. To systematically identify sources of EDS variance in sleepy and non-sleepy OSA patients, the specific aims of this study will determine: 1) state-specific variance related to sleep duration, obesity and fat distribution, specific comorbidities, and use of certain medications; 2) mis-estimation of severity of sleep disordered breathing from night-to-night variability in respiratory disturbances; 3) underlying trait associated with differential vulnerability to the sleepiness-producing effects of OSA. Using actigraphy and diaries to document sleep duration and both objective and subjective evaluations of sleepiness, Protocol A will classify 260 newly diagnosed OSA subjects as sleepy vs. non-sleepy and will document inter-individual differences in sleepiness among patients with similar disease severity caused by sleep history, obesity and fat distribution, specific comorbidities, and use of certain medications. Controlling for the variance identified in Protocol A, Protocol B will determine the degree to which inter-individual differences in sleepiness in 180 untreated OSA subjects with similar disease severity is a consequence of night-to-night variability in the occurrence of sleep disordered breathing documented by 7 consecutive nights of home sleep studies. Such night-to-night variability would reduce the reliability of single night determinations of apnea severity. Finally, in Protocol C we will determine if inter-individual differences in sleepiness remain after accounting for the variance explained by the clinical factors identified in Protocol A and the variance explained by mis-estimation of severity of sleep disordered breathing documented in Protocol B. In Protocol C, 60 patients (30 sleepy, 30 non-sleepy) will be matched on initial apnea severity and a set of a priori sleepiness factors will undergo 38 hrs of sleep deprivation in a laboratory to determine the existence of an underlying trait for daytime sleepiness.

本研究的目的是探讨在同等程度的阻塞性睡眠呼吸暂停（OSA）患者中观察到的差异性嗜睡的潜在操作机制。在给定的疾病严重程度水平内，即，在主观测量和客观测量的白天嗜睡中，都注意到睡眠期间呼吸紊乱的数量、个体间差异或对嗜睡的不同脆弱性。其原因 现象仍不清楚。对OSA患者管理的关键是了解与日间嗜睡发展相关的机制。我们假设在OSA严重程度相同的患者中，除了状态相关因素外，日间嗜睡（EDS）的差异还具有相当大的特质成分。为了系统地确定睡眠和非睡眠OSA患者EDS差异的来源， 本研究的具体目的是确定：1）与睡眠持续时间、肥胖和脂肪分布、特定合并症和某些药物的使用相关的状态特异性差异; 2）根据呼吸紊乱的夜间变化对睡眠呼吸紊乱的严重性的错误估计; 3）与对OSA的睡眠产生效应的不同脆弱性相关的潜在特征。使用活动记录仪和日记记录睡眠持续时间以及嗜睡的客观和主观评价，方案A将260名新诊断的OSA受试者分为嗜睡与非嗜睡，并将记录由睡眠史、肥胖和脂肪分布、特定合并症和使用某些药物引起的疾病严重程度相似的患者之间嗜睡的个体间差异。控制方案A中确定的方差，方案B将确定个体间 在180名具有相似疾病严重程度的未治疗OSA受试者中，嗜睡的差异是连续7个晚上的家庭睡眠研究记录的睡眠呼吸障碍发生的夜间变化的结果。这种夜间变化会降低呼吸暂停严重程度的单夜测定的可靠性。最后在 方案C我们将确定在考虑方案A中确定的临床因素解释的方差和方案B中记录的睡眠呼吸障碍严重程度的错误估计解释的方差后，嗜睡的个体间差异是否仍然存在。在方案C中，60名患者（30名嗜睡，30名非嗜睡）将在初始呼吸暂停严重程度上匹配，并且一组先验嗜睡因素将在实验室中经历38小时的睡眠剥夺，以确定日间嗜睡的潜在特征的存在。