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

• 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
• 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; 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

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.

该申请是为乔伊斯·李博士（Joyce S. Lee）颁发的K23奖。 科罗拉多州（CU）丹佛。职业目标：该K23奖将促进以下目标：（1）了解 遗传和基因组流行病学在间质性肺疾病（ILD）领域的应用； （2）获得 大数据分析的计算方法知识； （3）开发生物标志物测试的培训和 亚临床疾病状态的发展； （4）进行临床和翻译研究以更好 了解亚临床类风湿关节炎相关的ILD（RA-ELD）； （5）实现她的长期职业 成为ILD领域的独立临床和转化研究研究者的目标。 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领域的国际认可的科学家；迈克尔·霍尔斯（Michael Holers）博士（共同 导师），国际公认的早期RA免疫学调查专家；和研究 咨询委员会，包括塔莎·费格林博士（Tasha Fingerlin），专家统计遗传学家和遗传学 流行病学家和内容专家，包括凯文·迪恩（Kevin Deane）博士和吉尔·诺里斯（Jill Norris）博士。培训和环境： 她构建了一项严格的职业发展计划，其中包括特定的课程，高影响力 以CU为中心的研讨会和指导，该cu提供基础架构，资源和合作者 高影响临床研究所必需的。 研究目标：该研究建议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的死亡是 尽管RA死亡率总体下降，但仍在增加。早期检测亚临床RA-ELD将识别患者 肺部疾病负担较低，可能更可挽救的肺，并且可能揭示了新的分子靶标 对于在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：初步数据证明了RA-ILD和 特发性肺纤维化（IPF）。该提议利用了 了解IPF的已建立和亚临床形式。假设：有RA-ELD和IPF风险的患者 已经共享临床，遗传和生物学危险因素。目的：该研究建议将定义 表型和估计亚临床RA-ild的患病率（AIM 1），测试MUC5B变体的作用 亚临床RA-ild（AIM 2A），并在亚临床RA-ild中得出并验证生物标志物谱（AIM 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，并且 使用高分辨率计算机断层扫描鉴定的ILD异常。此信息将被使用 为了开发强大的风险预测算法，以识别临床环境中ILD风险最高的RA患者。 使用此队列，将研究与亚临床RA-ild相关的遗传和生物学因素。