Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting approximately 1% of the population, leading to significant morbidity and mortality.  In addition to immune-mediated joint injury, most patients also have other organ involvement, with lung disease seen in up to 80% of cases with RA.  Lung involvement, if present, leads to an even more profound negative impact on outcomes that seen in cases of RA with only joint involvement.  It is known that RA-related autoantibodies, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, can be detected years before symptoms develop in patients who eventually develop RA, allowing for early identification of healthy individuals who will later develop disease.  RA-related lung disease has been shown to be present early in the course of disease (<2 years of duration of joint symptoms), but it is unknown if lung disease can be detected in the preclinical RA period when these RA-related autoantibodies are present but joint disease is absent.  We propose that the presence of these antibodies in the pre-clinical period puts an individual at risk for RA-related lung injury - injury that if identified and treated prior to the development of symptoms may be halted before significant organ damage occurs.  We are assembling a unique cohort of subjects that consists of healthy first-degree relatives (FDRs) of patients with known RA.  As part of a funded R01, over the next 5 years we will be prospectively evaluating 2100 of these FDRs for the development of RA-related autoimmunity.  Our strategy with this study will be to identify and study subsets of individuals within this FDR group who exhibit highly predictive RA-related autoantibodies but do not meet classification criteria for the diagnosis of RA.  For this Cooperative Study Group for Autoimmune Disease Prevention Pilot Project (RA Lung Project), we propose to investigate the subset of this cohort that exhibits highly predictive RA-related autoantibodies for evidence of lung disease.  Modalities to determine RA lung disease will include symptom assessment, pulmonary function testing, high resolution computed tomography imaging, exhaled markers of inflammation, and serum markers of lung injury.  The goal of this project initially will be to determine the prevalence, timing, and risk factors for RA-related autoimmune lung disease in asymptomatic individuals with evidence of RA-related autoimmunity.  In addition, subjects identified with significant lung disease will benefit from early diagnosis and treatment evaluation.  Long-term goals of this RA Lung Project will include the development of a predictive model for lung disease in high-risk individuals, understanding of the temporal and immunologic relationship between articular manifestations and lung disease in RA, and identification of subjects with early RA-related lung disease who will be candidates for early intervention strategies.