Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease

项目总结 α-1抗胰蛋白酶缺乏(AATD)是慢性阻塞性疾病最常见的遗传原因 肺部疾病(COPD)。AATD患者的血浆AAT水平极低，一种丝氨酸 一种使中性粒细胞弹性蛋白酶和基质金属蛋白酶失活以维持 肺中的蛋白水解酶-抗蛋白酶酶平衡。尽管研究有助于理解 AATD的发病机制在其自然病程、治疗方法等方面仍有许多有待明确的地方 治疗策略和临床病程。有效的治疗方法的最根本障碍是 AATD是缺乏合适的生物标志物，这些标志物是疾病进展的特异性或与 特定的疾病表型。此外，我们对基因和基因缺乏完整的了解 这种疾病的表型特征。因此，目前的倡议将首先形成一个前瞻性的 AATD患者队列(Alpha-1临床队列，A1CC)，随后确定个体 通过合作的Alpha-1 Biomarker Research进入生物标记研究 财团(A1BReC)。在A1BReC的背景下，将进行基础研究，以 阐明该病的基因/表型关系，并探索进一步的机制研究。 AATD的发病机制。 UG3阶段：该阶段的主要目标是与阿尔法-1基金会合作，以 将目前的Alpha-1联系人登记簿放入完全集成和用户友好的Alpha-1临床 由阿尔法-1基金会管理的队列。A1CC将提供德意志银行的公共数据访问 通过i2b2查询模块识别的信息。次要目标是完成这项研究 协议、知情同意、程序手册、执行临床现场合同和获得IRB 批准议定书的UH3阶段。 UH3期：验证AATD人群血清和痰中生物标记物的假设 与肺部疾病相关的成像生物标记物可以预测预后和预后 肺部AATD患者的疾病和确定基因/表型的相关性 通过与无肺部疾病的AATD患者进行比较。

PROJECT SUMMARY Alpha-1 antitrypsin deficiency (AATD) is the most common genetic cause of chronic obstructive pulmonary disease (COPD). Individuals with AATD have extremely low levels of plasma AAT, a serine protease inhibitor that inactivates neutrophil elastase and matrix metalloproteinases to maintain the protease-antiprotease balance in the lung. Although research has contributed to an understanding of the pathogenesis of AATD much remains to be defined regarding its natural history, treatment strategies and clinical course. The most fundamental barrier to effective therapeutic approaches to AATD is a lack of suitable biomarkers that are specific for disease progression or correlate with a specific disease phenotype. Furthermore, we lack a complete understanding of the genetic and phenotypic characteristics of this disease. Therefore, the present initiative will first form a prospective cohort of individuals with AATD (Alpha-1 Clinical Cohort, A1CC) and subsequently identify individuals from that cohort to enter into a biomarker study through the collaborative Alpha-1 Biomarker Research Consortium (A1BReC). In the context of the A1BReC, fundamental studies will be performed to elucidate genotype/phenotype relationships in the disease and explore further mechanistic studies in the pathogenesis of AATD. UG3 Phase: The primary goal of this phase will be in collaboration with the Alpha-1 Foundation to place the present Alpha-1 contact registry into a fully integrated and user-friendly Alpha-1 Clinical Cohort managed by the Alpha-1 Foundation. The A1CC will provide for public data access of de- identified information through an i2b2 query module. The secondary goal is to finalize the study protocol, informed consent, manual of procedures, execute clinical site contracts and gain IRB approvals for the UH3 phase of the protocol. UH3 Phase: To test the hypothesis that biomarkers in serum and sputum of a population of AATD with lung disease will correlate with imaging biomarkers that can predict prognosis and outcome of disease and identify genotype/phenotype correlations in a population of AATD patients with lung disease through comparisons with AATD patients without lung disease.