SCOR IN CARDIOPULMONARY DISORDERS DURING SLEEP

SCOR申请中提出的研究旨在 基本机制、流行病学、诊断和临床结果 睡眠呼吸障碍（SDB） 在健康的人类受试者中， 在慢性仪器未麻醉的动物，我们将解决 睡眠的三个基本生理效应：a）地点和 低碳酸血症诱导的呼吸暂停的作用机制; B） 睡眠状态波动对呼吸稳定性的影响 和上呼吸道尺寸;以及c）睡眠诱导的 呼吸肌上气道阻力变化 招聘 四种类型的更狭窄的重点纵向， 面向临床的实验解决重要问题， 到SDB：a）高血压患者的体液机制 SDB; B）哮喘的细胞生物学; c） 肥胖及其对睡眠的影响 诱导的气道阻塞;以及d）应用 神经肌肉功能不全患者的睡眠呼吸暂停阈值 虚弱和慢性肺病作为间歇性 “休息”呼吸肌。 最后，我们最大的 这项事业使流行病学的焦点集中在以下问题上： 心肺睡眠障碍，根据绝对 对以人口为基础的样本进行纵向研究的必要性 以确定这些疾病的自然史。 我们 嵌套纵向研究设计，基于仔细考虑 的统计力量和先进的方法，将导致一个 正在进行的自然史、风险因素和 睡眠呼吸障碍的后果。 本研究的关键 是需要一个全面的，敏感的，有效的，定量的 测试睡眠呼吸障碍的基本特征， 适用于大量的受试者。 我们将设计和 验证这样的测试，并使用这些广泛而严格定义的数据， 基础，以确定睡眠呼吸障碍的预测因子， 它的临床后果在我们的人口为基础的研究。

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.