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

• 批准号: 10210437
• 负责人: Jeanine M D'Armiento
• 金额: $ 93.34万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10210437
• 关键词: Address; Biological; Biological Markers; Characteristics; Chest; Chronic Obstructive Airway 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

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.

项目摘要 α-1抗胰蛋白酶缺乏症（AATD）是慢性阻塞性的最常见遗传原因 肺部疾病（COPD）。 AATD患者的血浆AAT水平极低，丝氨酸 蛋白酶抑制剂，使中性粒细胞弹性酶和基质金属蛋白酶保持维持 蛋白酶 - 抗蛋白酶在肺中的平衡。尽管研究有助于理解 AATD的发病机理在其自然病史，治疗方面仍有许多待定义 策略和临床课程。有效治疗方法的最根本障碍 AATD缺乏适合疾病进展或与A相关的适当生物标志物 特定疾病表型。此外，我们对遗传和 该疾病的表型特征。因此，本计划将首先构成潜在的 与AATD（Alpha-1临床队列，A1CC）的个体队列，随后识别个体 从该队列开始，通过协作Alpha-1生物标志物研究进入生物标志物研究 财团（A1brec）。在A1BREC的背景下，将进行基本研究 阐明疾病中的基因型/表型关系，并探索进一步的机械研究 AATD的发病机理。 UG3阶段：此阶段的主要目标将与Alpha-1基金会合作 将当前的Alpha-1联系人注册表放入完全集成且用户友好的Alpha-1临床上 由Alpha-1基金会管理的队列。 A1CC将为DE-的公共数据访问提供 通过I2B2查询模块识别信息。次要目标是确定研究 协议，知情同意书，手册，执行临床现场合同并获得IRB 批准协议的UH3阶段。 UH3阶段：检验以下假设：AATD人群的血清和痰液中的生物标志物 与肺部疾病有关，将与可以预测预后和结果的成像生物标志物相关 疾病并确定肺AATD患者群体中的基因型/表型相关性 通过与没有肺部疾病的AATD患者进行比较，疾病。