Sleep Related Mechanisms of COPD Progression

项目3： 该项目将阐明睡眠呼吸障碍与睡眠质量加速下降之间的基本机制。 COPD的肺部和全身表现。它的总体假设是睡眠障碍 COPD中的呼吸触发肺部和全身炎症反应， 通过一种新的治疗策略减轻。将利用人和鼠模型的组合来 解决这个假设。人类研究旨在阐明睡眠的独特生理机制 COPD中的呼吸障碍，描述其对夜间氧合和全身炎症的影响， 并试验新的治疗方法，以防止COPD的加速下降。这些人类研究将对 来自COPD患者炎症特征和治疗试验的平行SCCOR研究的支持。在 补充鼠类研究，该项目将模拟睡眠中间歇性低氧血症的影响 呼吸紊乱，并与参与该SCCOR计划的基本肺生物学家合作，将解剖 COPD进展的基本分子抗形态发生和促炎机制。我们 该建议对COPD患者具有直接的临床意义。它将提供新的非侵入性 疾病进展的生理和血清标志物。这些标志物可用于COPD分层 发病率和死亡率风险增加的患者，针对特定患者亚组进行早期干预， 并监测治疗反应该项目将提供基础的分子，生理和 从人类和小鼠研究的独特组合中获得的治疗见解，最终将改善 COPD的健康结果。

PROJECT 3: This project will elucidate basic mechanisms linking sleep disordered breathing with accelerated decline in pulmonary and systemic manifestations of COPD. Its overall hypothesis is that sleep disordered breathing in COPD triggers pulmonary and systemic inflammatory responses, which can be mitigated by a novel therapeutic strategy. A combination of human and murine models will be utilized to address this hypothesis. Human studies are designed to elucidate unique physiologic mechanisms of sleep disordered breathing in COPD, characterize its impact on nocturnal oxygenation and systemic inflammation, and pilot novel therapy to prevent accelerated decline in COPD. These human studies will derive crucial support from parallel SCCOR studies of inflammatory profiles and therapeutic trials in COPD patients. In complementary murine studies, this project will model the effects of intermittent hypoxemia in sleep disordered breathing, and in concert with basic lung biologists involved in this SCCOR program, will dissect fundamental molecular antimorphogenic and proinflammatory mechanisms of COPD progression. Our proposal has immediate clinical implications for the patient with COPD. It will provide new non-invasive physiologic and serum markers of disease progression. These markers may be used to stratify COPD patients at increased risk of morbidity and mortality, target particular patient subgroups for early intervention, and monitor therapeutic responses. This project will provide fundamental molecular, physiologic and therapeutic insights from a unique combination of human and murine studies, which will ultimately improve health outcomes in COPD.