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）有关，与传统的骨质疏松症风险因素无关，包括物理不活跃，类固醇使用，AD恶病质。然而，由于缺乏对这组患者的骨质疏松术筛查指南的共识，COPD男性的骨质疏松症通常被诊断不足。系统性炎症在COPD和骨质疏松症的发病机理中起关键作用。但是很少有研究表明，特定的系统性炎症生物标志物与BMD低或随着时间的流逝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理，但自身免疫性在与COPD相关的骨质疏松症中的作用尚未研究。文献支持了低BMD和肺气肿之间的独立关联，但是该关联的机制尚不清楚。该项目的总体目标是确定与COPD男性的并发和进行性BMD损失和肺气肿相关的特定系统性炎症和自身免疫过程。这一目标将通过建立为期两年的纵向C o h o f m e f m e n w i t h c o p d，并获得基线和对BMD的两年评估，放射线释放性，N d肺功能。炎症生物标志物水平将以六个月的间隔和COPD急性加重（AECOPD）发作期间进行测量。通过双重X射线绝对测定法测量，与BMD损失相关的全身性炎症和自身免疫性生物标志物，通过定量CT扫描测量，在两年时间间隔内通过定量CT扫描和入射髋关节或椎骨骨折测量。还将评估全身性炎症和自身免疫性生物标志物水平的变化，以及与骨骼更新和累积BMD损失的关系。该项目的发现将确定具有加速BMD损失风险的男性COPD患者的标准，其中早期和串行BMD评估可能是有益的，可以深入了解与COPD和骨质疏松症联系起来的致病机制，并为COPD男性的骨质疏松症预防和治疗策略提供了新的目标。鉴于女性的大多数骨骼健康数据，该项目还将满足未满足的公共卫生需求。