SCOR IN CARDIOPULMONARY DISORDERS DURING SLEEP

在这个SCOR应用中提出的研究是针对 基本机制、流行病学、诊断和临床后果 睡眠呼吸障碍(SDB)。在健康的人体受试者和 在慢性仪器化非麻醉动物中，我们将解决 睡眠的三个基本生理效应：a)睡眠的部位和 低碳酸血症引起呼吸暂停的作用机制；b) 睡眠状态波动对呼吸稳定性的贡献 和上呼吸道尺寸；以及c)睡眠诱导的影响 呼吸肌上呼吸道阻力的变化 招聘。四种更窄聚焦的纵向， 面向临床的实验解决了相关的重要问题 对于SDB：A)高血压患者的体液机制 夜间哮喘的细胞生物学；c)影响 肥胖及其逆转对睡眠的程度和部位的影响- 诱导的呼吸道阻塞；以及d)应用 神经肌肉疾病患者睡眠呼吸暂停阈值的研究 虚弱和慢性肺部疾病作为间歇性疾病的手段 “休息”的呼吸肌。最后，我们最大的单一 企业带来了对流行病问题的关注 睡眠的心肺紊乱，基于绝对的 以人口为基础的样本纵向研究的必要性 以确定这些疾病的自然病史。我们的 基于仔细考虑的嵌套式纵向研究设计 统计能力和先进的方法，将导致一个 正在对自然历史、风险因素和 睡眠呼吸紊乱的后果。对这项研究至关重要 是否需要全面的、敏感的、有效的、量化的 测试睡眠障碍呼吸的基本特征， 适用于数量众多的科目。我们将设计和 验证这样的测试，并使用这个广泛且严格定义的数据 基础，以确定睡眠呼吸紊乱的预测因素和 它在我们基于人群的研究中的临床后果。

The research proposed in this SCOR application is aimed at the basic mechanisms, epidemiology, diagnosis and clinical consequences of sleep-disordered breathing (SDB). In healthy human subjects and in chronically instrumented unanesthetized animals, we will address three fundamental physiologic effects of sleep: a) the site and mechanism of action of hypocapnic-induced apnea; b) the contributions of fluctuating sleep state to breathing stability and upper airway dimensions; and c) the effects of sleep-induced changes in upper airway resistance on respiratory muscle recruitment. Four types of more narrowly focused longitudinal, clinically-oriented experiments address important issues related to SDB: a) humoral mechanisms of hypertension in the patient with SDB; b) cell biology of nocturnally-induced asthma; c) the effects of obesity and its reversal on the magnitude and site of sleep- induced airway obstruction; and d) application of the concept of the sleep-induced apneic threshold to patients with neuromuscular weakness and chronic lung disease as a means of intermittently "resting" respiratory muscles. Finally, our single largest undertaking brings an epidemiologic focus to the problem of cardiopulmonary disorders of sleep, predicated on the absolute necessity for longitudinal studies of a population-based sample in order to determine the natural history of these disorders. Our nested longitudinal study design, based on careful considerations of statistical power and advanced methods, will result in an ongoing elucidation of the natural history, risk factors and consequences of sleep disordered breathing. Critical to this study is the need for a comprehensive, sensitive, valid, quantitative test of the essential features of sleep disordered breathing, which is applicable to large numbers of subjects. We will design and validate such a test and use this broad and rigorously defined data base to determine the predictors of sleep disordered breathing and its clinical consequences in our population-based studies.