The Relationship Between Osteoporosis and Phenotypic Heterogeneity in COPD

骨质疏松症与慢性阻塞性肺病表型异质性的关系

基本信息

批准号：
8119503
负责人：
JESSICA BON
金额：
$ 13.03万
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：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8119503
关键词：
Algorithms Antibodies Attenuated Bioinformatics Biological Factors Biological Markers Biological Response Modifier Therapy Biometry Blocking Antibodies Body mass index Bone Density Bone Diseases Bone Marrow Bone Resorption Categories Cell Count Cell Culture Techniques Chronic Chronic Obstructive Airway Disease Classification Clinical Clinical Trials Collaborations Comorbidity Coronary Arteriosclerosis Cross-Sectional Studies Dentin Development Direct Costs Discipline Disease Disease Progression Ensure Environment Epidemiology Evaluation Evolution Facilities and Administrative Costs Fracture Frequencies Functional disorder Future Gonadal Hormones Heterogeneity Hip region structure Individual Inflammation Inflammation Mediators Inflammatory Interleukin-6 Laboratories Lead Learning Link Literature Longitudinal Studies Lung Lung diseases Measurement Measures Mediator of activation protein Medical Mentors Modeling Monitor Mononuclear Morbidity - disease rate Multiple Myeloma Natural History Nature Obstruction Oral Osteoclasts Osteogenesis Osteoporosis Outcome Assessment Patients Pattern Peripheral Peripheral Blood Mononuclear Cell Phenotype Physiological Prevalence Principal Investigator Process Pulmonary Emphysema Pulmonary Function Test/Forced Expiratory Volume 1 Research Research Personnel Resources Risk Risk Factors Screening procedure Series Serum Serum Markers Severities Skeletal Muscle Skeletal system Smoker Steroid therapy Steroids Subgroup Techniques Testing Therapeutic Time Training Tumor Necrosis Factor-alpha United States Universities Variant Vertebral column abstracting authority base bone loss bone metabolism burden of illness cigarette smoking clinical phenotype cohort disease phenotype driving force experience hormone deficiency inflammatory marker insight knowledge base mortality precursor cell research study skills symposium time interval

项目摘要

DESCRIPTION (provided by applicant): Studies show an increased prevalence of osteoporosis in individuals with chronic obstructive pulmonary disease (COPD), yet an understanding of the true prevalence, clinical implications, and mechanistic relationships remains limited. This proposal will determine the prevalence of decreased bone mineral density (BMD) and accelerated loss of BMD over time and its relationship to markers of bone resorption and formation within spirometrically defined categories of obstruction severity in a large cohort of current and former smokers with wide variability of airflow limitation. Radiographic, clinical, and serum marker phenotypes will be used to construct a classification and prediction model to identify COPD patients at greatest risk for osteoporosis and accelerated loss of BMD over time. Finally, a set of translational experiments will compare osteoclast formation and activity and its relationship to serum inflammatory mediators in COPD patients with and without decreased BMD and accelerated loss of BMD over time. These aims will define the COPD phenotype that should undergo osteoporosis screening, provide insight into the underlying mechanisms relating COPD and osteoporosis, and identify possible targets for screening and therapy. Training Plan: This proposal will provide the candidate with the unique opportunity to cross medical disciplines, expanding her COPD knowledge-base while developing a background in osteoporosis and bone metabolism. Through coursework and conferences, the candidate will acquire advanced training in biostatistics, epidemiology, and bioinformatics. Techniques learned in Dr. Roodman's laboratory through implementation of this proposal will equip the candidate with the skills necessary to communicate effectively during translational collaborations. The resources and experience of mentor Dr. Sciurba, an expert in COP clinical phenotyping and outcome assessment in clinical trials, and co-mentor Dr. Roodman, an authority on multiple myeloma and bone disease, combined with the robust research environment at the University of Pittsburgh, ensure the candidate's successful evolution to an independent investigator. (End of Abstract)

描述（由申请人提供）：研究表明，慢性阻塞性肺疾病（COPD）患者骨质疏松症患病率的增加，但对真正的患病率，临床意义和机械关系的理解仍然有限。该提案将确定骨矿物质密度降低（BMD）的患病率以及BMD随时间的加速损失，以及其与骨膜吸收和形成标志的关系，在具有广泛可变性的大量较大可变性的螺旋数定义的障碍物严重程度类别中气流限制。影像学，临床和血清标记表型将用于构建分类和预测模型，以鉴定COPD患者的骨质疏松症风险最大，并且随着时间的推移加速了BMD的损失。最后，一组翻译实验将比较破骨细胞的形成和活性及其与BMD降低和随着时间的加速BMD损失的COPD患者的血清炎症介质的关系。这些目标将定义COPD表型，该表型应经过骨质疏松症筛查，提供有关COPD和骨质疏松症与COPD和骨质疏松症相关的基本机制的见解，并确定筛查和治疗的可能目标。培训计划：该提案将为候选人提供跨越医学学科的独特机会，在发展骨质疏松症和骨骼代谢背景的同时，扩大了她的COPD知识群。通过课程和会议，候选人将获得生物统计学，流行病学和生物信息学的高级培训。通过实施该提案，在Roodman博士实验室中学到的技术将使候选人在翻译合作期间有效沟通所需的技能。临床试验中COP临床表型和成果评估专家Sciurba博士的资源和经验，以及多发性骨髓瘤和骨病的权威Roodman博士，加上大学生的强大研究环境。匹兹堡，确保候选人成功地演变为独立研究者。（抽象的结尾）