Phenotypes of Muscle Loss in Smokers

吸烟者肌肉损失的表型

• 批准号: 10463996
• 负责人: Richard Hang Zou
• 金额: $ 7.92万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10463996
• 关键词: Applications Grants; Biological Markers; Blood Banks; Blood specimen; Body Composition; Body mass index; Body measure procedure; Bone Mineral Contents; C-reactive protein; Cause of Death; Chronic Obstructive Pulmonary Disease; Clinical; Cohort Analysis; Complex; Cross-Sectional Studies; Data; Data Store; Disease; Disease Progression; Dual-Energy X-Ray Absorptiometry; Early Intervention; Environment; Evaluation; Fatty acid glycerol esters; Foundations; Future; General Population; Goals; Height; Impairment; Individual; Inflammatory; Interleukin-6; Intervention; K-Series Research Career Programs; Longitudinal Studies; Longitudinal cohort; Lung diseases; Measures; Mentors; Mentorship; Methodology; Modeling; Molecular; Morbidity - disease rate; Muscle; Muscular Atrophy; Natural History; Outcome; Phenotype; Physicians; Physiological; Positioning Attribute; Proteins; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Quality of life; Research; Respiratory Signs and Symptoms; Risk; Risk Factors; Role; Scientist; Severity of illness; Smoker; Subgroup; Sum; Surrogate Markers; TNF gene; Testing; Thinness; Time; TimeLine; Training; United States; Universities; Vital capacity; Walking; airway obstruction; base; career; clinical phenotype; clinical risk; cohort; comorbidity; demographics; disease phenotype; disorder risk; exercise intolerance; experience; former smoker; functional decline; functional disability; functional status; health related quality of life; high risk population; indexing; inflammatory marker; insight; lean body mass; meter; molecular phenotype; mortality; multilevel analysis; muscle form; pulmonary function; radiological imaging; reduced muscle mass; respiratory; systemic inflammatory response; trend

PROJECT SUMMARY/ABSTRACT Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States and worldwide. Decreased muscle mass is common in COPD and associates with lung disease severity, functional impairment, systemic inflammation, and all-cause mortality. Fat free mass index (FFMI), defined by the sum of whole-body lean muscle and bone mineral content adjusted for height in meters squared, is an accepted surrogate marker of whole-body muscle mass in COPD. FFMI associates with lung function and is an independent predictor of mortality in individuals with COPD who have normal BMI. However, most studies evaluating FFMI in COPD are cross-sectional and do not examine changes in FFMI over time. These longitudinal studies are critical to identify the clinical and molecular phenotype of individuals at greatest risk for disease morbidity and mortality. Additionally, most studies focused primarily on current and former smokers with airflow obstruction, defined by a ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) <0.70. Yet, smokers without airflow obstruction remain at risk for emphysema, respiratory symptoms, and respiratory exacerbations compared with the general population. Our preliminary data show that longitudinal muscle mass changes in smokers are not modified by airflow obstruction status, and that a subset of smokers both with and without airflow obstruction demonstrates a significant decrease in FFMI over time. In this study, we will leverage our well- characterized longitudinal cohort of current and former smokers with and without airflow obstruction who have serial clinical, physiologic, and radiographic data, FFMI data determined from readily available dual energy x-ray absorptiometry (DXA), and banked blood samples to test our primary hypotheses that distinct trajectories of muscle mass change are associated with specific clinical and molecular phenotypes and that rapid FFMI decline correlates with lung disease progression and functional impairments over time. In Aim 1, I will determine trajectories of FFMI change in smokers with and without airflow obstruction and identify important baseline clinical and molecular predictors of muscle loss trajectories. In Aim 2, I will compare longitudinal changes in lung function, emphysema, functional status, and circulating inflammatory proteins between smokers with rapid FFMI decline and smokers without rapid FFMI decline. This study proposal will provide important insight into the natural history of muscle loss in smokers with and without airflow obstruction and help establish specific clinical and molecular phenotypes associated with rapid muscle mass decline for targetable interventions in future studies. This training plan, combined with close mentorship and a robust research environment at the University of Pittsburgh, will facilitate my transition to a mentored Career Development Award and, ultimately, to an independent career as a physician-scientist.

项目总结/文摘