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

项目摘要 α-1抗胰蛋白酶缺乏症（AATD）是慢性阻塞性肺疾病最常见的遗传原因。 肺疾病（COPD）。AATD患者血浆AAT水平极低， 一种蛋白酶抑制剂，使中性粒细胞弹性蛋白酶和基质金属蛋白酶失活， 蛋白酶-抗蛋白酶平衡。虽然研究有助于了解 AATD的发病机制在其自然史、治疗 策略和临床过程。有效治疗方法的最根本障碍是 AATD缺乏对疾病进展具有特异性或与疾病进展相关的合适的生物标志物。 特定疾病表型。此外，我们缺乏对基因和 这种疾病的特征。因此，目前的举措将首先形成一个前瞻性的 AATD个体队列（α-1临床队列，A1 CC），随后确定个体 通过Alpha-1生物标志物研究合作， 财团（A1 BReC）。在A1 BReC的背景下，将进行基础研究， 阐明疾病的基因型/表型关系，并探索进一步的机制研究， AATD的发病机制。 UG 3阶段：该阶段的主要目标是与Alpha-1基金会合作， 将目前的Alpha-1接触登记系统纳入完全集成和用户友好的Alpha-1临床 由Alpha-1基金会管理。A1 CC将提供公共数据访问， 通过i2 b2查询模块识别信息。第二个目标是完成研究 方案、知情同意书、程序手册，签署临床试验机构合同并获得IRB批准 方案UH 3阶段的批准。 UH 3阶段：检验AATD人群血清和痰液中的生物标志物 将与可以预测预后和肺部疾病结局的成像生物标志物相关。 在患有肺结核的AATD患者群体中， 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.