Rheumatoid Arthritis-associated Parenchymal Lung Disease: Clinical and Molecular Phenotypes

项目摘要/摘要 类风湿性关节炎(RA)是一种全身性炎症性疾病，在美国约有150万人受到影响 美国。尽管包括间质性肺疾病(ILD)和 肺气肿，是类风湿性关节炎常见的肺部并发症，患病率和死亡率不断上升，目前尚无对策 目前存在对进行性疾病的早期检测或风险分层。这是一个未得到满足的需求领域 可能导致更多的干预机会和减少相当大的发病率和 类风湿性关节炎相关性实质性肺病的死亡率。 在这项建议中，我们的目标是全面描述类风湿性关节炎的早期实质性肺部疾病的特征，并确定风险。 进展性疾病的因素。我们假设临床和分子风险因素可以预测 类风湿性关节炎相关实质性肺病的发生和发展，包括临床前ILD(PreILD) 和肺气肿，进行性RA-PreILD的分子图谱将与纤维性RA-ILD重叠。至 检验这一假设，我们将提出以下建议：在具体目标1中，我们将确定流行率和 应用目视和客观的放射学方法和 将这些测量与功能容量、呼吸道症状和与健康相关的生活质量联系起来 评估。在具体目标2中，我们将定义临床和分子决定因素来预测 类风湿性关节炎肺气肿的发生发展及与正常对照组的比较 PreILD提供对RA引起的实质性肺损伤的不同模式的机械洞察力。在……里面 具体目标3，我们将证明进行性RA-PreILD和纤维性RA-ILD具有相似的分子 签名，表明表型和机制重叠。为了实现这项提案的目标，a 200名无ILD病史的RA患者的纵向队列将接受长达6年的跟踪调查，详细说明 临床、功能、放射学和分子表型。 这项研究的成功完成将使我们更好地了解早期 类风湿关节炎相关性ILD和肺气肿的特点和自然病史及建立新的非侵入性研究 识别进展性疾病风险人群的方法。这将使更密切的监控和更早的 提供干预机会，有可能降低患者的发病率和死亡率 患有类风湿性关节炎相关的肺实质疾病。

PROJECT SUMMARY / ABSTRACT Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting approximately 1.5 million people in the United States. Although parenchymal lung disease, which encompasses interstitial lung disease (ILD) and emphysema, is a common lung complication of RA with increasing prevalence and mortality, no strategies currently exist for early detection or risk stratification of progressive disease. This is an area of unmet need that could lead to improved opportunities for intervention and a decrease in the considerable morbidity and mortality of RA-associated parenchymal lung disease. In this proposal, we aim to fully characterize early parenchymal lung disease in RA and establish risk factors for progressive disease. We hypothesize that clinical and molecular risk factors can predict the development and progression of RA-associated parenchymal lung disease, including preclinical ILD (preILD) and emphysema, and that the molecular profile of progressive RA-preILD will overlap with fibrotic RA-ILD. To test this hypothesis, we will propose the following: In Specific Aim 1, we will determine the prevalence and progression of RA-associated preILD and emphysema using visual and objective radiologic approaches and correlate these measurements with functional capacity, respiratory symptoms, and health-related quality of life assessments. In Specific Aim 2, we will define clinical and molecular determinants that predict the development and progression of RA emphysema and compare the molecular profile of emphysema with preILD to provide mechanistic insight into the divergent patterns of parenchymal lung injury caused by RA. In Specific Aim 3, we will demonstrate that progressive RA-preILD and fibrotic RA-ILD have similar molecular signatures, suggesting phenotypic and mechanistic overlap. To achieve the aims of this proposal, a longitudinal cohort of 200 RA patients without a history of ILD will be followed for up to 6 years with detailed clinical, functional, radiologic, and molecular phenotyping. The successful completion of this research will provide us with a better understanding of the early characteristics and natural history of RA-associated ILD and emphysema and establish novel non-invasive ways to identify those at risk for progressive disease. This will enable closer monitoring and earlier opportunities for intervention, potentially leading to decreased morbidity and mortality in individuals afflicted with RA-associated parenchymal lung disease.