Clinical and Molecular Characteristics of Rheumatoid Arthritis-associated ILD

 描述（由申请人提供）：研究风湿性关节炎（RA）是一种全身性炎症性疾病，影响美国约130万人。间质 肺部疾病（ILD）是RA常见的肺部并发症，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，这些类型的肺纤维化具有呼吸道症状增加和功能减退，但对RA相关ILD的特征和自然史知之甚少。一些研究表明，存在一系列RA相关ILD，其中约10%的RA患者患有晚期疾病，另外30%患有早期疾病，其中一半将进展。吸烟者的早期ILD与呼吸道症状轻度增加、总肺容量减少和功能减退相关;然而，这些结果在RA人群中尚未得到很好的表征。还已经表明，将外周血分子标记物添加到这些临床参数中可以增强对患有纤维化肺病的个体的评估和诊断。 在本职业发展计划中，申请人假设RA相关ILD将与一系列放射学变化、功能减退、呼吸道症状和外周血分子标志物相关。她建议从这些功能和分子特征中创建一个临床预测评分，以提高对早期和晚期疾病受试者的识别。具体而言，在她的第一个目标中，她将探索早期和晚期RA相关ILD与功能减退（通过肺功能测试和6分钟步行距离测量）和呼吸道症状之间的关系。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志物，并将这些标志物与功能障碍的程度相关联。在她的第三个目标中，她将建立一个临床预测评分，并在一个独立的队列中验证该评分。为了实现这一提议的目的，将开发一个具有良好特征的早期和晚期ILD RA患者队列，为未来的纵向研究提供宝贵的资源。 本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风险人群，并更好地了解RA相关ILD的特征和自然史。这将使受影响的个体能够更密切地监测和早期治疗，可能导致RA相关ILD患者的发病率和死亡率降低。申请人的长期职业目标是成为一名独立的临床/转化NIH资助的研究者，专注于以患者为导向的肺部研究。为了实现这一目标，她的短期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，申请人将获得必要的临床和科学专业知识以及出版记录，以将其定义为类风湿性关节炎（RA）个体间质性肺病（ILD）领域的权威。这将通过一个职业发展计划来实现，该计划将正式的教学法，包括先进的流行病学，生物统计学，生物标志物和编程课程，与会议出席，临床活动以及她的导师，顾问和合作者的多学科团队的指导和支持相结合。通过她的研究经验和职业发展计划获得的技能和科学知识的独特组合及其在RA相关ILD领域的应用将帮助她建立独立于导师团队的能力，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进行其拟议的研究和职业发展/培训活动。她将工作的部门是一个丰富的研究环境，具有杰出的导师，学术领导和智力互动的历史。该机构非常重视申请人的成功职业发展，包括提供所有必要的设施，资源和设备，以促进她的职业发展和她的申请中提出的研究。此外，她将有充分的机会获得一个强大的和良好的特征化的类风湿关节炎受试者队列，以及与多个地方和国家机构的合作安排。这一点，与她完成导师和多学科咨询委员会与专业知识直接相关的领域，她的研究相结合，确保她提出的研究和她的职业发展计划的目标是合理的，适当的，可行的。

 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.