MECHANISMS OF DIFFERENTIAL SLEEPINESS IN SLEEP APNEA

这项建议的目的是探索在同等程度的阻塞性睡眠呼吸暂停(OSA)患者中观察到的不同嗜睡的潜在操作机制。在给定的疾病严重程度内，即睡眠期间呼吸紊乱的次数，个体之间的差异，或对困倦的不同易感性，在主观测量和客观测量的白天嗜睡中都被注意到。这样做的原因是 这一现象目前尚不清楚。对阻塞性睡眠呼吸暂停综合征患者的治疗至关重要的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，白天嗜睡(EDS)的差异除了与状态相关的因素外，还具有实质性的特征成分。为了系统地确定睡眠和非睡眠阻塞性睡眠呼吸暂停患者EDS差异的来源， 这项研究的具体目标将确定：1)与睡眠持续时间、肥胖和脂肪分布、特定的合并症和某些药物的使用有关的特定状态的差异；2)由于呼吸障碍的夜间变异性而误判睡眠呼吸障碍的严重程度；3)与OSA引起嗜睡影响的不同易感性相关的潜在特征。使用活动记录仪和日记来记录睡眠时间以及对困倦的客观和主观评估，A方案将把260名新诊断的阻塞性睡眠呼吸暂停综合征患者归类为嗜睡和不困倦，并将记录由于睡眠史、肥胖和脂肪分布、特定的共病以及某些药物的使用而导致疾病严重程度相似的患者的困倦程度的个体差异。对议定书A中确定的差异进行控制，议定书B将确定个体间 在180名疾病严重程度相似的未经治疗的阻塞性睡眠呼吸暂停患者中，嗜睡程度的差异是连续7个晚上的家庭睡眠研究记录的睡眠呼吸紊乱发生率夜间变化的结果。这种夜间变化会降低单夜测定呼吸暂停严重程度的可靠性。最后，在 在C方案中，60名患者(30名困倦，30名不困)将在初始呼吸暂停严重程度上进行匹配，一组先验嗜睡因素将在实验室接受38小时的睡眠剥夺，以确定是否存在白天嗜睡的潜在特征。

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.