Autoimmunity and emphysema and risk of osteoporosis in smokers

吸烟者的自身免疫和肺气肿以及骨质疏松症的风险

基本信息

批准号：
9916794
负责人：
JESSICA BON
金额：
$ 38.5万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9916794
关键词：
Age Alveolar Macrophages Antibodies Autoantibodies Autoimmune Process Autoimmune Responses Autoimmunity Binding Binding Proteins Biological Assay Biological Markers Bone Density Cachexia Cause of Death Cells Chronic Obstructive Airway Disease Data Dentin Diagnostic radiologic examination Disease Disease Progression Endoplasmic Reticulum Enzyme-Linked Immunosorbent Assay Female Foundations Fracture Future Goals Heat shock proteins High Prevalence Human Immune Targeting Immune response Immunoglobulin G Immunohistochemistry Immunologic Markers Immunologics Immunomodulators In Vitro Incidence Inflammation Mediators Inflammatory Investigational Therapies Link Literature Longitudinal cohort Lung diseases Measurement Measures Mediating Molecular Molecular Chaperones Morbidity - disease rate NF-kappa B Natural History Osteoclasts Osteoporosis Osteoporosis prevention Participant Pathogenesis Pathogenicity Pathologic Patient Selection Patients Physical activity Physiological Population Prevalence Prevention strategy Process Production Proteins Pulmonary Emphysema Reaction Time Reverse Transcriptase Polymerase Chain Reaction Risk Risk Factors Risk stratification Roentgen Rays Role Scanning Series Smoker Smoking Status Stains Steroids Testing United States Variant Woman X-Ray Computed Tomography airway obstruction biological adaptation to stress bone bone resorbing activity bone turnover clinically significant cohort cytokine endoplasmic reticulum stress falls follow-up glucose-regulated proteins improved insight male men mortality novel nuclear factors of activated T-cells osteoporosis with pathological fracture patient population physical inactivity precursor cell public health relevance pulmonary function response screening guidelines smoking-related lung disease targeted agent tartrate-resistant acid phosphatase time interval tool treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Low bone mineral density (BMD) has been linked to chronic obstructive pulmonary disease (COPD) independent of traditional osteoporosis risk factors including steroid use, cachexia, and decreased physical activity. Although the increased prevalence of osteoporosis contributes to morbidity and mortality in COPD patients, little is known regarding indications for BMD assessment or osteoporosis mechanisms in this susceptible population. The rate of BMD loss is an independent risk factor for fracture. Yet, cross-sectional dual x-ray absorptiometry (DXA) assessment of BMD provides no information about rate of BMD decline. Immunologic alterations 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 emphysema and low BMD has been supported by the literature, but the mechanism for this association is also unknown. This project's overall goal is to study how specific autoimmune processes relate to concurrent emphysema progression and accelerated BMD decline in male and female smokers with lung disease. This goal will be accomplished through extension to six years of an already established longitudinal cohort with pre- existing baseline and two-year assessments of BMD, radiographic emphysema, pulmonary function, and autoimmune biomarker levels. The association of an autoimmune biomarker, anti-glucose regulated protein 78 (GRP78) IgG, with emphysema progression, measured by quantitative CT scan, and BMD loss, measured by serial DXA, over the six-year time interval will be studied in smokers with emphysema or airflow obstruction. A series of in vitro osteoclast studies will be performed to assess the effect of autoantibodies to GRP78, an endoplasmic reticulum (ER) chaperone protein intimately involved in the ER stress response, on osteoclast formation, proliferation, and activity. The findings from this project will identify criteria for smokers at risk of accelerated BMD loss in whom early and serial measurements of BMD may be warranted, provide insight into pathogenic mechanisms linking emphysema and osteoporosis, and provide novel targets for osteoporosis prevention and treatment strategies in patients with COPD.

描述：低骨矿物质密度（BMD）与慢性阻塞性肺部疾病（COPD）有关骨质疏松症的风险因素，包括类固醇的使用和降低的体育锻炼。或骨质疏松率的机制。文献尚未研究与COPD相关的骨质疏松症的自身免疫性。 BMD，放射学肺气肿功能和自身免疫性生物标志物水平的前端基线和两年评估。通过串行DXA，将在吸烟者的六年时间间隔内进行肺气肿或气流阻塞。 ER应力反应，破骨细胞的形成生命和活动。确定具有加速BMD损失风险的吸烟者的标准，其中早期和串行测量可能是将肺气肿和骨质疏松症PD连接起来的IC机制。