Clinical and Molecular Characteristics of Rheumatoid Arthritis-associated ILD

类风湿性关节炎相关 ILD 的临床和分子特征

• 批准号: 8821786
• 负责人: Tracy Jennifer Doyle
• 金额: $ 16.33万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8821786
• 关键词: Accounting; Address; Adult; Advisory Committees; Affect; Age; Area; Biological Markers; Biometry; Blood; CXC Chemokines; Carbon Monoxide; Case-Control Studies; Cessation of life; Characteristics; Chest; Clinical; Clinical Research; Clinical/Radiologic; Collection; Complement; Complication; Data; Development; Development Plans; Diagnosis; Diffuse; Disease; Disease Outcome; Early treatment; Enrollment; Ensure; Environment; Epidemiology; Equipment; Fibrosis; Funding; Future; Goals; Hamman-Rich syndrome; Hospitals; Individual; Inflammatory; Institution; Interstitial Lung Diseases; Knowledge; Lead; Leadership; Ligands; Longitudinal Studies; Lung; Lung diseases; Matrilysin; Matrix Metalloproteinases; Measures; Mentors; Mentorship; Modeling; Molecular; Monitor; Morbidity - disease rate; Natural History; Outcome; Pathologic; Patients; Physiological; Population; Prevalence; Publications; Pulmonary Fibrosis; Pulmonary Surfactant-Associated Protein A; Pulmonary function tests; Questionnaires; Recording of previous events; Research; Research Personnel; Resources; Rheumatoid Arthritis; Rheumatoid Factor; Risk; Severities; Smoker; Staging; Stratification; Symptoms; Total Lung Capacity; Training Activity; United States; United States National Institutes of Health; Universities; Vital capacity; Walking; Woman; Work; X-Ray Computed Tomography; advanced disease; authority; base; beta-Chemokines; career; career development; clinically significant; cohort; cyclic citrullinated peptide; experience; follow-up; functional disability; improved; inflammatory lung disease; interstitial; molecular marker; mortality; multidisciplinary; novel; patient oriented; peripheral blood; predictive modeling; programs; public health relevance; research and development; respiratory; skills; symposium

 DESCRIPTION (provided by applicant): Research Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting approximately 1.3 million people in the United States. Interstitial lung disease (ILD) is a common lung complication of RA with increasing prevalence and mortality. Although RA-associated ILD is similar to other types of lung fibrosis, which are well known to have increased respiratory symptoms and functional decrements, little is known about the characteristics and natural history of RA-associated ILD. Some studies have suggested that there is a spectrum of RA-associated ILD with approximately 10% of RA patients having advanced disease, and another 30% with early disease, half of whom will progress. Early ILD in smokers has been associated with mildly increased respiratory symptoms, reduced total lung capacity, and functional decrements; however these findings have not been well characterized in an RA population. It has also been shown that the addition of peripheral blood molecular markers to such clinical parameters may enhance the assessment and prognostication of individuals with fibrotic lung diseases. In this career development proposal, the applicant hypothesizes that RA-associated ILD will be associated with a spectrum of radiologic changes, functional decrements, respiratory symptoms, and peripheral blood molecular markers. She proposes to create a clinical prediction score from these functional and molecular characteristics to improve the identification of subjects with both early and advanced disease. Specifically, in her first aim, she will explore the relationship between early and advance RA-associated ILD with respect to functional decrements, as measured by lung function testing and the distance walked in six minutes, and respiratory symptoms. In her second aim, she will identify peripheral blood molecular markers that are associated with RA-associated ILD, and correlate those markers with the degree of functional impairment. In her third aim, she will build a clinical prediction score and validate this score in an independent cohort. To achieve the aims of this proposal, a cohort of well-characterized RA patients with early and advanced ILD will be developed, providing an invaluable resource for future longitudinal studies. The successful completion of this research will provide us with novel non-invasive ways to identify those at risk for RA-associated ILD as well as a better understanding of the characteristics and natural history of RA- associated ILD. This will enable closer monitoring and earlier treatment of affected individuals, potentially leading to decreased morbidity and mortality in individuals afflicted with RA-associated ILD. Candidate The applicant's long-term career goal is to become an independent clinical/translational NIH funded investigator focused on patient-oriented pulmonary research. In order to achieve this goal, her short-term career objectives are to acquire the clinical research, quantitative, and analytical skills necessary to complete the proposed research and become an independent patient-oriented researcher. Additionally the applicant will obtain the clinical and scientific expertise and publication record necessary to define herself as an authority in the field of interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This will be accomplished through a career development plan that integrates formal didactics, including advanced epidemiology, biostatistics, biomarker, and programming courses, with conference attendance, clinical activities, and the guidance and support of her multidisciplinary team of mentors, advisors, and collaborators. The unique combination of skills and scientific knowledge gained through her research experience and career development plan and their application to the field of RA-associated ILD will help her to establish independence from her mentorship team and prepare her to achieve her long-term career goal. Environment The applicant will perform her proposed research and career development / training activities at a world- renowned major academic institution. The division in which she will work is a rich research environment with an outstanding history of mentorship, academic leadership, and intellectual interaction. This institution is very invested in the applicant's successful career development, including making available all the facilities, resources, and equipment necessary for her career enhancement and the research proposed in her application. In addition, she will have full access to a robust and well-characterized cohort o rheumatoid arthritis subjects, as well as collaborative arrangements with multiple local and national institutions. This, combined with her accomplished mentors and multidisciplinary advisory committee with expertise in areas directly relevant to her research, ensures that her proposed research and the goals of her career development plan are well-reasoned, appropriate, and feasible.

 描述（由申请人提供）： 研究类风湿性关节炎 (RA) 是一种全身性炎症性疾病，影响着美国大约 130 万人。 肺部疾病 (ILD) 是 RA 的一种常见肺部并发症，其患病率和死亡率不断增加，尽管 RA 相关 ILD 与其他类型的肺纤维化相似，众所周知，后者会增加呼吸道症状和功能下降，但人们对这种疾病知之甚少。一些研究表明，RA 相关 ILD 存在一定范围，大约 10% 的 RA 患者患有晚期疾病，另外 30% 患有早期疾病，其中一半会出现早期疾病。吸烟者的早期 ILD 与呼吸道症状轻度增加、肺活量减少和功能减退有关；然而，这些发现在 RA 人群中尚未得到很好的表征。此类临床参数可能会增强对纤维化肺病患者的评估和预后。在本职业发展提案中，申请人认为 RA 相关 ILD 将与一系列放射学变化、功能下降、呼吸道症状和外周血有关。她建议根据这些功能和分子特征创建临床预测评分，以改善对早期和晚期疾病受试者的识别，具体而言，她将探索早期和晚期 RA 相关 ILD 之间的关系。在她的第二个目标中，她将确定与 RA 相关 ILD 相关的外周血分子标记，并将这些标记与相关联。功能障碍的程度。为了实现该提案的目标，她将建立一个临床预测评分并在一个独立队列中验证该评分，将开发一组具有良好特征的早期和晚期 ILD 的 RA 患者，为未来的纵向研究提供宝贵的资源。这项研究的成功完成将为我们提供新的非侵入性方法来识别 RA 相关 ILD 的风险，并更好地了解 RA 相关 ILD 的特征和自然史，这将使我们能够进行更密切的监测。以及对受影响个体进行早期治疗，可能导致病情下降患有 RA 相关 ILD 的个体的发病率和死亡率 申请人的长期职业目标是成为 NIH 资助的独立临床/转化研究者，专注于以患者为导向的肺部研究。职业目标是获得完成拟议研究所需的临床研究、定量和分析技能，并成为一名独立的以患者为导向的研究人员。此外，申请人还将获得将自己定义为该领域权威所需的临床和科学专业知识以及出版记录。的领域这将通过职业发展计划来完成，该计划包括高级流行病学、生物统计学、生物标志物和课程规划，包括会议出席、临床活动和指导。她的导师、顾问和合作者组成的多学科团队的支持，通过她的研究经验和职业发展计划及其在 RA 相关 ILD 领域的应用获得的技能和科学知识的独特组合将帮助她建立独立于导师团队的地位，并为实现长期职业目标做好准备。 环境 申请人将在世界知名的主要学术机构中开展她提议的研究和职业发展/培训活动。丰富的研究环境，具有杰出的指导、学术领导和智力互动的历史，该机构对申请人的成功职业发展投入很大，包括为她的职业发展和提出的研究提供必要的所有设施、资源和设备。此外，她还可以完全访问强大的应用程序。和特征明确的类风湿性关节炎受试者队列，以及与多个地方和国家机构的合作安排，再加上她卓有成效的导师和在与她的研究直接相关的领域具有专业知识的多学科咨询委员会，确保了她提出的研究和研究。她的职业发展规划目标合理、适当、可行。