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）与慢性阻塞性肺疾病（COPD）相关，与传统的骨质疏松症风险因素无关，包括缺乏运动、类固醇使用、恶病质。然而，由于对COPD男性患者的骨质疏松症筛查指南缺乏共识，这类患者的骨质疏松症往往诊断不足。全身炎症在COPD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随着时间的推移骨密度加速损失之间存在关系。免疫学改变同样有助于COPD和骨质疏松症的发病机制，但自身免疫在COPD相关骨质疏松症中的作用尚未研究。低BMD和肺气肿之间的独立关联已得到文献的支持，但这种关联的机制尚不清楚。该项目的总体目标是确定与COPD男性患者并发和进行性BMD丢失和肺气肿相关的特定全身炎症和自身免疫过程。这一目标将通过建立一个为期两年的纵向C O P D模型，并获得基线和两年的BMD、放射学肺气肿和肺功能评估来实现。将在COPD急性加重（AECOPD）发作期间每6个月测量一次炎症生物标志物水平。将确定与BMD损失相关的全身炎症和自身免疫生物标志物，通过双X线吸收测定法测量，通过定量CT扫描测量肺气肿进展，以及在两年时间间隔内发生的髋关节或椎骨骨折。还将评估AECOPD患者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丢失的关系。该项目的研究结果将确定有加速BMD丢失风险的男性COPD患者的标准，早期和连续的BMD评估可能是有益的，为COPD和骨质疏松症的致病机制提供深入了解，并为COPD男性骨质疏松症的预防和治疗策略提供新的靶点。鉴于大多数骨骼健康数据都是关于妇女的，该项目还将解决尚未满足的公共卫生需求。