Clinical and Molecular Characteristics of Rheumatoid Arthritis-associated ILD

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 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.