Rheumatoid Arthritis Patients at Risk for Interstitial Lung Disease

类风湿关节炎患者面临间质性肺病的风险

基本信息

批准号：
9755483
负责人：
Joyce Sujin Lee
金额：
$ 19.21万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-16 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9755483
关键词：
Address Advisory Committees Affect Age Aging Algorithms Area Autoantibodies Autoimmune Process Automobile Driving Big Data Biological Biological Factors Biological Markers Cessation of life Characteristics Clinical Clinical Research Colorado Data Data Analyses Development Development Plans Diagnosis Diagnostic Discipline Disease Dyspnea Early Diagnosis Educational workshop Elements Enrollment Environment Epidemiologist Gender Gene Expression Gene Proteins Genes Genetic Genetic Markers Genomics Goals Hamman-Rich syndrome Health High Resolution Computed Tomography Immune response Immunologics Impairment Inflammatory Arthritis Infrastructure Institution International Interstitial Lung Diseases Investigation K-Series Research Career Programs Knowledge Lead Length Link Lung Lung diseases MUC5B gene Measures Medical Genetics Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Molecular Molecular Genetics Molecular Target Mutation Outcome Outpatients Pathogenicity Pathway interactions Patients Pattern Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Phenotype Prevalence Prevention Measures Prevention strategy Primary Prevention Progressive Disease Research Research Personnel Research Proposals Resources Rheumatoid Arthritis Risk Risk Factors Role Scanning Scientist Secondary Prevention Severities Signal Transduction Smoking Smoking History Telomerase Testing Time Training Translational Research Universities Variant Work base biomarker panel burden of illness career career development cigarette smoking clinical epidemiology cohort disease diagnosis effective intervention genetic epidemiology genetic variant genome sciences genomic epidemiology high risk idiopathic pulmonary fibrosis insight male mortality novel prediction algorithm professor promoter public health relevance skills surfactant telomere

项目摘要

This application is for a K23 award for Dr. Joyce S. Lee, an Assistant Professor at the University of Colorado (CU) Denver. Career Goals: This k23 award will facilitate the following goals: (1) to understand the application of genetic and genomic epidemiology in the field of interstitial lung disease (ILD); (2) to gain knowledge in computational approaches to big data analysis; (3) to develop training in biomarker testing and development in subclinical disease states; (4) to conduct clinical and translational investigations to better understand subclinical rheumatoid arthritis-associated ILD (RA-ILD); and (5) to achieve her long-term career goal of becoming an independent clinical and translational research investigator in the field of ILD. Mentorship: To achieve these goals, Dr. Lee has assembled a mentoring team comprised of Dr. David Schwartz (primary mentor), an internationally recognized scientist in the field of ILD; Dr. Michael Holers (co- mentor), an internationally recognized expert in the immunologic investigations of early RA; and a research advisory committee that includes Dr. Tasha Fingerlin, an expert statistical geneticist and genetic epidemiologist, and content experts including Dr. Kevin Deane and Dr. Jill Norris. Training and Environment: She has constructed a rigorous career development plan that includes specific coursework, high-impact workshops, and mentorship, centered at CU, which provides the infrastructure, resources and collaborators necessary for high impact clinical research. Research Objective: The overall goal of this research proposal is to define the clinical and molecular/genetic phenotype of subclinical RA-ILD. Relationship to Health: Deaths from RA-ILD are increasing despite an overall decline in RA mortality. Early detection of subclinical RA-ILD will identify patients with a lower burden of lung disease, potentially more salvageable lung, and may reveal novel molecular targets for intervention that are effective in the subclinical and/or early clinical stages of this progressive disease. Rationale: Preliminary data demonstrate clinical, genetic and biologic similarities between RA-ILD and idiopathic pulmonary fibrosis (IPF). This proposal leverages the progress that has been made in the understanding of established and subclinical forms of IPF. Hypothesis: Patients at risk for RA-ILD and IPF have shared clinical, genetic, and biological risk factors. Aims: This research proposal will define the phenotype and estimate the prevalence of subclinical RA-ILD (Aim 1), test the role of the MUC5B variant in subclinical RA-ILD (Aim 2A), and derive and validate a biomarker profile in subclinical RA-ILD (Aim 2B). Approach: To address this hypothesis and accomplish these aims, 400 RA patients will be enrolled and abnormalities of ILD identified using high-resolution computed tomography scans. This information will be used to develop a robust risk prediction algorithm to identify RA patients at highest risk for ILD in the clinical setting. Using this cohort, the genetic and biologic factors associated with subclinical RA-ILD will be investigated.

此申请是为新加坡大学助理教授 Joyce S. Lee 博士申请 K23 奖学金科罗拉多州 (CU) 丹佛。职业目标：这个 k23 奖项将促进以下目标：（1）了解遗传学和基因组流行病学在间质性肺疾病（ILD）领域的应用； (2) 获得大数据分析计算方法的知识； (3) 开展生物标志物检测培训亚临床疾病状态的发展； (4) 开展临床和转化研究，以更好地了解亚临床类风湿性关节炎相关 ILD (RA-ILD)； (5) 实现她的长期职业生涯目标是成为 ILD 领域的独立临床和转化研究研究者。指导：为了实现这些目标，李博士组建了一个由大卫博士组成的指导团队 Schwartz（主要导师），ILD领域国际公认的科学家；迈克尔·霍勒斯 (Michael Holers) 博士（共同导师），国际公认的早期 RA 免疫学研究专家；和一项研究顾问委员会成员包括统计遗传学家和遗传学专家 Tasha Fingerlin 博士流行病学家和内容专家，包括 Kevin Deane 博士和 Jill Norris 博士。培训及环境：她制定了严格的职业发展计划，包括具体的课程作业、高影响力的职业发展计划以 CU 为中心的研讨会和指导，提供基础设施、资源和合作者高影响力的临床研究所必需的。研究目标：本研究计划的总体目标是定义临床和亚临床 RA-ILD 的分子/遗传表型。与健康的关系：RA-ILD 导致的死亡是尽管 RA 死亡率总体下降，但仍在增加。亚临床 RA-ILD 的早期检测将识别患者肺部疾病负担较低，肺部可能更容易挽救，并可能揭示新的分子靶标对于这种进行性疾病的亚临床和/或早期临床阶段有效的干预措施。理由：初步数据表明 RA-ILD 和 RA-ILD 之间的临床、遗传和生物学相似性特发性肺纤维化（IPF）。该提案利用了已取得的进展了解 IPF 的既定形式和亚临床形式。假设：有 RA-ILD 和 IPF 风险的患者具有共同的临床、遗传和生物学风险因素。目的：本研究提案将定义表型并估计亚临床 RA-ILD 的患病率（目标 1），测试 MUC5B 变异在亚临床 RA-ILD（目标 2A），并推导和验证亚临床 RA-ILD 的生物标志物谱（目标 2B）。方法：为了解决这一假设并实现这些目标，将招募 400 名 RA 患者并使用高分辨率计算机断层扫描识别 ILD 异常。该信息将被使用开发稳健的风险预测算法，以识别临床环境中 ILD 风险最高的 RA 患者。将利用该队列研究与亚临床 RA-ILD 相关的遗传和生物学因素。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Essential Components of an Interstitial Lung Disease Clinic: Results From a Delphi Survey and Patient Focus Group Analysis.

间质性肺病诊所的基本组成部分：德尔菲调查和患者焦点小组分析的结果。

DOI：
发表时间：
2021
期刊：
影响因子：
9.6
作者：
Graney, Bridget A;He, Christophe;Marll, Michael;Matson, Scott;Bianchi, Pauline;Cosgrove, Gregory P;Lee, Joyce S;PFF CCN Delphi Collaborators
通讯作者：
PFF CCN Delphi Collaborators

New trajectories in the treatment of interstitial lung disease: treat the disease or treat the underlying pattern?

间质性肺疾病治疗的新轨迹：治疗疾病还是治疗根本模式？