Sleep Related Mechanisms of COPD Progression

项目3： 该项目将阐明睡眠呼吸紊乱与睡眠加速下降有关的基本机制。 慢性阻塞性肺疾病的肺部和全身表现。它的总体假设是睡眠紊乱 COPD患者的呼吸会触发肺部和全身炎症反应，这可能是 通过一种新的治疗策略来缓解。人类和小鼠模型的组合将被用来 应对这一假设。人体研究旨在阐明睡眠的独特生理机制。 COPD患者的呼吸紊乱，表征了其对夜间氧合和全身炎症的影响， 并试点新的治疗方法，以防止COPD加速下降。这些人体研究将得出至关重要的结论 COPD患者炎症特征和治疗试验的平行SCCOR研究支持。在……里面 作为对小鼠的补充研究，该项目将模拟间歇性低氧血症对睡眠的影响 呼吸紊乱，并与参与这个SCCOR计划的基础肺生物学家合作，将解剖 慢性阻塞性肺疾病进展的基本分子抗形态发生和促炎机制。我们的 该方案对COPD患者有直接的临床意义。它将提供新的非侵入性 疾病进展的生理和血清标记物。这些标志物可用于对COPD进行分层 发病和死亡风险增加的患者，针对特定的患者亚组进行早期干预， 并监测治疗反应。该项目将提供基本的分子、生理和 来自人类和小鼠研究的独特组合的治疗见解，这最终将改善 慢性阻塞性肺病的健康结局。

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.