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

Alpha-1 抗胰蛋白酶疾病队列：疾病的纵向生物标志物研究

基本信息

批准号：
10514976
负责人：
Jeanine M D'Armiento
金额：
$ 117.79万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-20 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10514976
关键词：
Address Biological Biological Markers Characteristics Chest Chronic Obstructive Pulmonary Disease Clinical Clinical Data Clinical Research Clinical Trials Collaborations Contracts DNA Data Databases Dimensions Disease Disease Outcome Disease Progression Enhancers Enrollment Equilibrium Foundations Fractals Funding Generations Genes Genetic Genetic Polymorphism Genotype Goals Heritability Image In Vitro Individual Inflammatory Response Informed Consent Injury Institution Institutional Review Boards Knowledge Leukocyte Elastase Link Liver diseases Longitudinal cohort Lung Lung diseases Manuals Matrix Metalloproteinases Measurement Measures Mechanics Mutation Natural History Participant Pathogenesis Patient Care Patients Peptide Hydrolases Phase Phenotype Plasma Population Preparation Procedures Prognosis Prospective cohort Protease Inhibitor Protocols documentation Pulmonary Emphysema Registries Research Research Infrastructure Research Personnel Role Secure Series Serine Proteinase Inhibitors Serum Severities Sputum Testing Time Validation airway remodeling alpha 1-Antitrypsin alpha 1-Antitrypsin Deficiency base biomedical informatics clinical heterogeneity clinical research site clinically relevant cohort data access data sharing disease heterogeneity disease phenotype exome sequencing imaging biomarker imaging modality immune function improved induced pluripotent stem cell macrophage multidisciplinary novel novel marker participant retention promoter prospective pulmonary function decline recruit response specific biomarkers therapeutically effective treatment strategy user-friendly

项目摘要

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.

项目概要 Alpha-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部疾病（慢性阻塞性肺病）。患有 AATD 的人血浆 AAT（一种丝氨酸）水平极低蛋白酶抑制剂，使中性粒细胞弹性蛋白酶和基质金属蛋白酶失活，以维持肺中的蛋白酶-抗蛋白酶平衡。尽管研究有助于理解 AATD 的发病机制在其自然史、治疗方面仍有许多待确定策略和临床过程。有效治疗方法的最根本障碍 AATD 缺乏特定于疾病进展或与疾病相关的合适生物标志物特定的疾病表型。此外，我们对遗传和基因缺乏完整的了解。本病的表型特征。因此，本次倡议首先要形成一个前瞻性的患有 AATD 的个体队列（Alpha-1 临床队列，A1CC）并随后识别个体从该队列中通过 Alpha-1 生物标志物合作研究进入生物标志物研究联盟 (A1BReC)。在 A1BReC 的背景下，将进行基础研究阐明疾病中的基因型/表型关系并探索进一步的机制研究 AATD 的发病机制。 UG3 阶段：该阶段的主要目标是与 Alpha-1 基金会合作将现有的 Alpha-1 联系人注册表放入完全集成且用户友好的 Alpha-1 临床中由 Alpha-1 基金会管理的队列。 A1CC 将提供 de- 的公共数据访问通过 i2b2 查询模块识别信息。第二个目标是完成研究协议、知情同意书、程序手册、执行临床中心合同并获得 IRB 批准该协议的 UH3 阶段。 UH3 阶段：检验 AATD 人群血清和痰中生物标志物的假设与肺部疾病相关的成像生物标志物可以预测预后和结果疾病并确定患有肺部疾病的 AATD 患者群体的基因型/表型相关性通过与没有肺部疾病的 AATD 患者进行比较来了解疾病。