DEFINING PHENOTYPIC TRAITS IN OBSTRUCTIVE SLEEP APNEA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在本研究中，目的是在一组具有广泛呼吸紊乱指数（RDI）的个体中确定以下变量对呼吸暂停存在和严重程度的相对贡献：a）咽部解剖结构（MRI和Pcrit），B）NREM睡眠期间咽扩张肌对增加机械负荷的反应性，c）呼吸控制稳定性（环路增益），d）唤醒阈值。 这些变量将被建模为每个个体呼吸暂停严重程度的预测因子，以定义不同的呼吸暂停表型。 据推测，将有五个或六个分组的表型性状（聚类分析），将导致阻塞性睡眠呼吸暂停或防止其发展。 该提案还旨在确定呼吸暂停表型是否预测对某些形式的治疗的反应性：1）氧气管理或乙酰唑胺，这两者都稳定呼吸控制，改善睡眠呼吸暂停患者不稳定的呼吸控制（高回路增益）？ 2)镇静剂给药（如曲唑酮）是否能改善低唤醒阈值（即容易从睡眠中醒来，这会使呼吸更加多变并促进睡眠呼吸暂停）患者的睡眠呼吸暂停？

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In this study, the aim is to define the relative contribution of the following variables to both apnea presence and severity in a group of individuals with a wide range of respiratory disturbance index (RDI): a) pharyngeal anatomy (MRI and Pcrit), b) pharyngeal dilator muscle responsiveness to increasing mechanical load during NREM sleep, c) ventilatory control stability (loop gain), d) arousal threshold. These variables will be modeled as predictors of apnea severity in each individual to define the different apnea phenotypes. It is hypothesized that there will be five or six groupings of the phenotypic traits (cluster analysis) that will either cause obstructive sleep apnea or prevent its development. This proposal also aims to determine if apnea phenotype predicts responsiveness to certain forms of therapy: 1) Does oxygen administration or acetazolamide, both of which stabilize the control of breathing, improve sleep apnea in patients with unstable ventilatory control (high loop gain)? 2) Does sedative administration, such as Trazodone, improve sleep apnea in patients identified as having a low arousal threshold (i.e. awaken easily from sleep, which would make breathing more variable and promote sleep apnea)?