Emphysema and Inflammatory Biomarkers and Risk of Osteoporosis in Men with COPD

肺气肿和炎症生物标志物以及男性慢性阻塞性肺病患者骨质疏松症的风险

• 批准号: 9551566
• 负责人: JESSICA BON
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9551566
• 关键词: Acute; Address; Alveolar Macrophages; Animal Model; Antibodies; Autoantibodies; Autoantigens; Autoimmune Process; Autoimmunity; Binding; Biological Markers; Bone Density; Bone Resorption; Cachexia; Cells; Chronic Obstructive Airway Disease; Consensus; Data; Diagnostic radiologic examination; Endoplasmic Reticulum; Female; Fibrinogen; Fracture; Frequencies; Future; Goals; Guidelines; Health; Hip Fractures; Human; IL6 gene; Immunologics; Incidence; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interleukin-6; Knowledge; Link; Literature; Longitudinal cohort; Low Prevalence; Measures; Mediating; Molecular Chaperones; Morbidity - disease rate; Obstructive Lung Diseases; Osteoclasts; Osteoporosis; Osteoporosis prevention; Pathogenesis; Pathogenicity; Pathologic; Patients; Play; Population; Prevalence; Prevention strategy; Process; Production; Proteins; Public Health; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Risk; Risk Factors; Roentgen Rays; Role; Smoker; Spinal Fractures; Steroids; Symptoms; Testing; Time; Translations; Veterans; Woman; X-Ray Computed Tomography; bone; bone loss; bone turnover; circulating biomarkers; endoplasmic reticulum stress; epidemiology study; glucose-regulated proteins; human model; insight; male; men; mortality; novel; osteoporosis with pathological fracture; osteoporotic bone; physical inactivity; precursor cell; predictive marker; promoter; prospective test; public health relevance; pulmonary function; response; screening; skeletal; targeted treatment; time interval; treatment strategy

 DESCRIPTION (provided by applicant): Low bone mineral density (BMD) is associated with chronic obstructive lung disease (COPD) independent of traditional osteoporosis risk factors, including physical inactivity, steroid use, ad cachexia. However, osteoporosis in men with COPD is often underdiagnosed due to lack of consensus on osteoporosis screening guidelines in this group of patients. Systemic inflammation plays a key role in the pathogenesis of both COPD and osteoporosis; but few studies have shown a relationship between specific systemic inflammatory biomarkers and either low BMD or accelerated loss of BMD over time. Immunologic alterations likewise contribute to the pathogenesis of both COPD and osteoporosis but the role of autoimmunity in COPD-related osteoporosis has not been studied. An independent association between low BMD and emphysema has been supported by the literature, but the mechanism for this association is unknown. This project's overall goal is to identify specific systemic inflammatory and autoimmune processes associated with both concurrent and progressive BMD loss and emphysema in men with COPD. This goal will be accomplished by establishing a two-year longitudinal c o h o r t o f m e n w i t h C O P D and attaining baseline and two-year assessments of BMD, radiographic emphysema, a n d pulmonary function. Inflammatory biomarker levels will be measured at six month intervals and during episodes of acute exacerbation of COPD (AECOPD). Systemic inflammatory and autoimmune biomarkers associated with BMD loss, measured by dual x-ray absorptiometry, emphysema progression, measured by quantitative CT scan, and incident hip or vertebral fractures over the two-year time interval will be identified. Changes in systemic inflammatory and autoimmune biomarker levels with AECOPD and the relationship to bone turnover and cumulative BMD loss will also be assessed. The findings from this project will identify criteria for male COPD patients at risk of accelerated BMD loss in whom early and serial BMD assessments may be beneficial, provide insight into pathogenic mechanisms linking COPD and osteoporosis, and provide novel targets for osteoporosis prevention and treatment strategies in men with COPD. This project will also address an unmet public health need given that most data on skeletal health are in women.

 描述（由申请人提供）： 低骨矿物质密度 (BMD) 与慢性阻塞性肺病 (COPD) 相关，独立于传统的骨质疏松症危险因素，包括身体活动不足、类固醇使用、恶病质。然而，由于缺乏共识，患有慢性阻塞性肺病的男性骨质疏松症经常被漏诊。骨质疏松症筛查指南在这组患者中，全身炎症在慢性阻塞性肺病和骨质疏松症的发病机制中发挥着关键作用；但很少有研究表明特定的全身炎症生物标志物与低骨密度或骨质疏松症之间的关系。随着时间的推移，免疫学改变会加速慢性阻塞性肺病和骨质疏松症的发病机制，但自身免疫在慢性阻塞性肺病相关骨质疏松症中的作用尚未得到文献支持。这种关联的机制尚不清楚，该项目的总体目标是确定与 COPD 男性并发和进行性 BMD 损失和肺气肿相关的特定全身炎症和自身免疫过程。通过建立为期两年的纵向 COPD 并达到 BMD、放射学肺气肿和肺功能的基线和两年评估来完成。将每隔六个月和在 COPD 急性加重（AECOPD）发作期间测量炎症生物标志物水平。通过双 X 射线吸收测定法测量与 BMD 损失相关的炎症和自身免疫生物标志物，通过 CT 扫描测量的肺气肿进展以及两年时间间隔内发生的髋部或椎骨骨折也将被定量确定，AECOPD 引起的全身炎症和自身免疫生物标志物水平的变化以及与骨转换和累积 BMD 损失的关系也将被评估。该项目的研究结果将确定面临 BMD 加速损失风险的男性 COPD 患者的标准，对这些患者进行早期和连续的 BMD 评估可能是有益的，深入了解 COPD 和骨质疏松症之间的致病机制，并为治疗骨质疏松症提供新的靶点。鉴于大多数骨骼健康数据都来自女性，该项目还将解决未满足的公共卫生需求。