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.

项目概要/摘要 类风湿性关节炎 (RA) 是一种全身性炎症性疾病，影响着大约 130 万人。 美国。间质性肺疾病 (ILD) 是 RA 的常见肺部并发症，且患病率不断增加 和死亡率。尽管 RA 相关 ILD 与其他类型的肺纤维化相似，但人们对 RA 相关 ILD 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 的疾病。一些研究表明，存在一系列与 RA 相关的 ILD，其中大约 10% 的 RA 患者患有晚期疾病，另外 30% 患有早期疾病，其中一半会进展。 研究还表明，临床危险因素和外周血分子标记物可能会增强 RA 相关 ILD 患者的评估和预后。 在该提案中，申请人假设由风险因素组成的临床预测模型， 功能减退以及分子和遗传标记可以预测疾病的发展和进展 早期和晚期疾病。具体来说，在她的第一个目标中，她将评估风险的能力 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/或功能减退可以增强该临床预测模型的性能。在她身上 第二个目标是，她将通过充分表征来确定风险评分是否与疾病进展相关 BRASS 和 TRAIL1 人群中进行性亚临床和临床明显的 RA 相关 ILD 关于临床表现、呼吸道症状、功能减退和分子标记。在她的第三次 她的目标是确定与 RA 相关 ILD 的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。为了实现 为了实现该提案的目标，一组具有良好特征的患有早期和晚期 ILD 的 RA 患者将 通过详细的分子和遗传表型进行开发，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颖的非侵入性方法来识别那些 进行性 RA 相关 ILD 的风险以及更好地了解其特征和自然 早期疾病史。这将使受影响的个人能够得到更密切的监测和更早的治疗， 可能会降低患有 RA 相关 ILD 的个体的发病率和死亡率。