Molecular and Cellular Determinants of Disease Heterogeneity in COPD

匹兹堡大学在慢性阻塞性肺疾病方面的研究建立在我们对慢性阻塞性肺疾病的长期研究传统的基础上 阻塞性肺病提出四个项目提案，扩展我们之前的工作和我们的 与不列颠哥伦比亚大学密切合作。 在项目1中，COPD表型异质性的外周标志物；我们的全球 假设：COPD是一组不同的可定义的解剖和生理疾病过程，每一种 它有自己的分子和细胞过程来决定疾病的表现和进展；这将 在800名患者中进行测试。 在项目2中，我们假设适应性免疫在COPD中诱导了AIRWA损伤。 由同源识别和对多肽抗原的反应驱动的过程，导致或促成了 导致COPD进展的呼吸道损伤；这将在人类肺移植组织中进行主要测试。 在项目3EGR-1：慢性阻塞性肺疾病的细胞凋亡和炎症调节中，我们将转化结果 从人体组织实验到小鼠模型，以确定早期生长反应(EGR-1)， 在香烟环境中调节细胞凋亡和炎症途径的协调表达 吸烟引起的慢性阻塞性肺疾病(COPD)。 在项目4中，我们假设COPD患者的气雾剂免疫治疗的临床研究 用特定的生物制剂调节COPD受试者的已识别免疫反应将消融或 改善COPD的发病机制，改变其自然病程。

The University of Pittsburgh SCORR in COPD builds upon our long tradition of research in Chronic Obstructive Pulmonary Disease to propose a four project proposal which extends our previous work and our strong collaboration with the University of British Columbia. In project 1 PERIPHERAL MARKERS OF PHENOTYPIC HETEROGENEITY IN COPD; Our global hypothesis: COPD is a heterogeneous group of definable anatomic and physiologic disease processes, each with its own molecular and cellular processes that determine disease manifestation and progression; this will be tested in a well characterized cohort of 800 patients. In project 2 ADAPTIVE IMMUNE-INDUCED AIRWA INJURY IN COPD, we postulate that adaptive immune processes, driven by cognate recognition and responses to peptide antigens, cause or contribute to the airway injuries that result in COPD progression; this will be tested largely in human lung explants. In project 3 EGR-1: REGULATOR OF APOPTOSIS AND INFLAMMATION IN COPD we will translate results from human tissue experiments into mouse models to determine whether early growth response (EGR-1), regulates the coordinated expression of apoptosis and inflammation pathways in the context of cigarette smoke-induced chronic obstructive pulmonary disease (COPD). In project 4 CLINICAL INVESTIGATION OF AEROSOL IMMUNOTHERAPY IN COPD we hypothesize that modulation of identified immune responses in COPD subjects with specific biologic agents will ablate or ameliorate pathogenic mechanisms and alter the natural history of COPD.