Molecular and Genetic Characteristics of Progressive Rheumatoid Arthritis-associated Interstitial Lung Disease

进行性类风湿关节炎相关间质性肺病的分子和遗传特征

• 批准号: 9810481
• 负责人: Tracy Jennifer Doyle
• 金额: $ 6.69万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9810481
• 关键词: Address; Adult; Affect; Age; Auscultation; Autoantibodies; Biological Markers; Blood; CCL18 gene; Characteristics; Clinical; Clinical/Radiologic; Collection; Complication; Data; Development; Diagnosis; Disease; Disease Outcome; Disease Progression; Early treatment; Future; Gender; Genetic; Genetic Markers; Genetic Polymorphism; Hamman-Rich syndrome; Histologic; Hospitals; Incidence; Individual; Inflammatory; Interstitial Lung Diseases; Lead; Length; Longitudinal Studies; Longitudinal cohort; Lung; MUC5B gene; Modeling; Molecular; Molecular Genetics; Monitor; Morbidity - disease rate; Natural History; Patients; Pattern; Performance; Phase; Phenotype; Physiological; Pirfenidone; Population; Prevalence; Progressive Disease; Pulmonary Fibrosis; Pulmonary Surfactant-Associated Protein D; Radiology Specialty; Research; Resources; Respiratory Signs and Symptoms; Rheumatoid Arthritis; Risk; Risk Factors; Risk stratification; Scanning; Smoker; Smoking; Specificity; Time; Treatment outcome; United States; Woman; Work; X-Ray Computed Tomography; advanced disease; base; clinical predictors; clinical risk; cohort; disease diagnosis; follow-up; idiopathic pulmonary fibrosis; improved; improved outcome; interstitial; male; molecular marker; mortality; novel; peripheral blood; predictive modeling; prognostic; promoter; screening; telomere

PROJECT SUMMARY / ABSTRACT 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, little is known about the molecular and genetic characteristics and natural history of RA-associated ILD, both early and advanced forms of disease. 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. It has also been shown that clinical risk factors and peripheral blood molecular markers may enhance the assessment and prognostication of individuals with RA-associated ILD. In this proposal, the applicant hypothesizes that a clinical predictive model composed of risk factors, functional decrements, and molecular and genetic markers can predict the development and progression of both early and advanced forms of disease. Specifically, in her first aim, she will assess the ability of a risk score to identify subclinical and clinically-evident RA-ILD and evaluate if pulmonary auscultation, respiratory symptoms, and/or functional decrements can enhance the performance of this clinical predictive model. In her second aim, she will determine if the risk score correlates with disease progression through fully characterizing progressive subclinical and clinically-evident RA-associated ILD in the BRASS and TRAIL1 populations with respect to clinical findings, respiratory symptoms, functional decrements, and molecular markers. In her third aim, she will identify genetic markers associated with the development and progression of RA-associated ILD to determine if they can improve the ability of the clinical model to identify progressive disease. To achieve the aims of this proposal, a longitudinal cohort of well-characterized RA patients with early and advanced ILD will be developed with detailed molecular and genetic phenotyping, 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 progressive RA-associated ILD as well as a better understanding of the characteristics and natural history of early disease. 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.

项目总结/摘要 风湿性关节炎（RA）是一种全身性炎症性疾病，在美国约有130万人受到影响。 美国的间质性肺疾病（ILD）是RA常见的肺部并发症，患病率不断增加 and mortality.尽管RA相关ILD与其他类型的肺纤维化相似，但对RA相关ILD的机制知之甚少。 RA相关ILD（早期和晚期形式）的分子和遗传特征以及自然史 疾病。一些研究表明，存在一系列RA相关ILD， 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。 临床危险因素和外周血分子标志物也可增强 RA相关ILD个体的评估和说明。 在该提案中，申请人假设由风险因素组成的临床预测模型， 功能减退，分子和遗传标记可以预测的发展和进展， 早期和晚期的疾病。具体来说，在她的第一个目标，她将评估的能力，一个风险 评分以识别亚临床和临床明显的RA-ILD，并评估肺部听诊、呼吸 症状和/或功能减少可以增强该临床预测模型的性能。在她 第二个目标是，她将通过充分表征风险评分是否与疾病进展相关， BRASS和TRAIL 1人群中进行性亚临床和临床明显RA相关ILD， 关于临床发现、呼吸道症状、功能减退和分子标记物。在她的第三 目的是确定与RA相关ILD发生和进展相关的遗传标记 以确定它们是否可以提高临床模型识别进展性疾病的能力。实现 为了实现这一目标，一个具有良好特征的早期和晚期ILD RA患者的纵向队列将 开发详细的分子和遗传表型，为未来提供宝贵的资源， 纵向研究。 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那些在 进行性RA相关ILD的风险，以及更好地了解RA相关ILD的特征和自然 早期疾病史。这将有助于更密切地监测和更早地治疗受影响的个人， 可能导致RA相关ILD患者的发病率和死亡率降低。