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

类风湿性关节炎相关的肺实质疾病：临床和分子表型

• 批准号: 10446060
• 负责人: Tracy Jennifer Doyle
• 金额: $ 70.83万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10446060
• 关键词: Accounting; Activities of Daily Living; Address; Adult; Affect; Airway Disease; Area; Autoimmunity; Biological Markers; Cause of Death; Cessation of life; Characteristics; Chronic; Chronic Obstructive Pulmonary Disease; Clinical; Complication; Data; Development; Disease; Early Diagnosis; Early Intervention; Early identification; Gene Expression Profile; Gene Expression Profiling; Health Status; High Prevalence; Hospitalization; Individual; Inflammation; Inflammatory; Injury; Interstitial Lung Diseases; Intervention; Knowledge; Lead; Literature; Longitudinal cohort; Lung; Lung diseases; MUC5B gene; Measurement; Measures; Methods; Molecular; Molecular Profiling; Monitor; Morbidity - disease rate; Natural History; Outcome; Patients; Pattern; Persons; Phenotype; Physiological; Populations at Risk; Predisposition; Prevalence; Progressive Disease; Publishing; Pulmonary Emphysema; Quality-of-Life Assessment; Radiology Specialty; Recording of previous events; Research; Respiratory Signs and Symptoms; Rheumatoid Arthritis; Risk; Risk Factors; Scoring Method; Smoking; Stress; Testing; Time; United States; Usual Interstitial Pneumonia; Variant; Visual; Work; biomarker discovery; biomarker signature; clinical phenotype; clinical risk; effective therapy; fibrotic lung disease; follow-up; health related quality of life; high risk; improved; improved outcome; insight; interstitial; lung injury; molecular phenotype; mortality; novel; patient screening; pre-clinical; pulmonary function; risk stratification; transcriptome sequencing

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.

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 150 万人。 美国。尽管实质性肺疾病，包括间质性肺疾病（ILD）和 肺气肿是 RA 的一种常见肺部并发症，患病率和死亡率不断增加，目前尚无治疗策略 目前存在用于进展性疾病的早期检测或风险分层的方法。这是一个未满足需求的领域 可能导致干预机会的改善和发病率的大幅降低 RA 相关肺实质疾病的死亡率。 在本提案中，我们的目标是全面描述 RA 早期实质肺病的特征并确定风险 疾病进展的因素。我们假设临床和分子危险因素可以预测 RA 相关肺实质疾病的发生和进展，包括临床前 ILD (preILD) 和肺气肿，并且进行性 RA-preILD 的分子特征将与纤维化 RA-ILD 重叠。到 检验这一假设，我们将提出以下建议：在具体目标 1 中，我们将确定患病率和 使用视觉和客观放射学方法观察 RA 相关的 preILD 和肺气肿的进展，以及 将这些测量值与功能能力、呼吸道症状和健康相关的生活质量相关联 评估。在具体目标 2 中，我们将定义预测的临床和分子决定因素 RA 肺气肿的发生和进展，并比较肺气肿的分子特征 preILD 为 RA 引起的实质肺损伤的不同模式提供机制见解。在 具体目标 3，我们将证明进行性 RA-preILD 和纤维化 RA-ILD 具有相似的分子水平 特征，表明表型和机制重叠。为了实现本提案的目标， 由 200 名无 ILD 病史的 RA 患者组成的纵向队列将被随访长达 6 年，并详细了解 临床、功能、放射学和分子表型分析。 这项研究的成功完成将使我们对早期的研究有更好的了解。 RA 相关 ILD 和肺气肿的特征和自然史，并建立新型非侵入性治疗方法 识别那些有进展性疾病风险的方法。这将使更密切的监测和更早的 干预的机会，有可能降低受影响个体的发病率和死亡率 患有 RA 相关的肺实质疾病。