The epigenetics of exercise and physical activity in COPD

慢性阻塞性肺病 (COPD) 中运动和体力活动的表观遗传学

• 批准号: 10326333
• 负责人: Emily S Wan
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326333
• 关键词: Accreditation; Activities of Daily Living; Acute; Aerobic Exercise; Affect; Algorithms; Anxiety; Biological; Blood; Blood specimen; Body Composition; Boston; Caring; Cause of Death; Cessation of life; Chronic Obstructive Airway Disease; Clinical; DNA; DNA Methylation; Data; Development; Disease; Dyspnea; Education; Educational Intervention; Enrollment; Environmental Exposure; Epidemiology; Epigenetic Process; Exercise; Exhibits; Exposure to; Future; Gene Expression; Genes; Genetic; Genome; Genomics; Goals; Guidelines; Healthcare; Heterogeneity; Hospitalization; Hospitals; Impairment; Internet; Intervention; Length; Macronutrients Nutrition; Measurement; Measures; Mediating; Medical; Medical Records; Mental Depression; Metabolism; Methylation; Morbidity - disease rate; Muscle; Nutritional; Obstructive Lung Diseases; Outcome; Pathway interactions; Patients; Pattern; Pharmaceutical Preparations; Physical activity; RNA; Rehabilitation therapy; Risk; Risk Factors; Sampling; Site; Source; Spirometry; Structure; Supervision; Telephone Interviews; Training; Training Programs; United States; Variant; Veterans; Walking; Work; algorithm development; base; bead chip; clinical practice; clinically relevant; cohort; design; disability; exercise capacity; exercise intervention; exercise training; genome-wide; health care service utilization; health related quality of life; improved; individual response; inflammatory marker; insight; longitudinal analysis; methylation pattern; modifiable risk; mortality; muscle form; novel; pedometer; personalized medicine; precision medicine; predicting response; preservation; programs; prospective; pulmonary function; pulmonary rehabilitation; recruit; response; risk stratification; sedentary lifestyle; strength training; symptomatic improvement; systemic inflammatory response; treatment program; treatment strategy

Chronic obstructive pulmonary disease (COPD) is highly prevalent among U.S. Veterans and is a significant source of morbidity and mortality. Patients with COPD frequently have reduced exercise capacity (defined as a patient's maximal capacity to perform work) and levels of physical activity (a term frequently used to describe a patient's typical daily level of activity). Reduced exercise capacity and physical activity are correlated with significant clinical outcomes, such as disability, all-cause mortality, and healthcare utilization rates. Importantly, exercise capacity and physical activity represent potentially modifiable risk factors in COPD. Exercise training, which is typically performed in the setting of a structured pulmonary rehabilitation program, is currently endorsed by the Global Initiative for Obstructive Lung Diseases (GOLD) guidelines as an essential component of the non-pharmacological management of COPD and has been shown to improve symptoms and health-related quality of life while reducing healthcare utilization. In addition to formal pulmonary rehabilitation, novel programs which focus on improving daily physical activity may provide similar benefits. In addition to the disease-specific benefits above, exercise training and increased physical activity have also been associated with systemic changes such as improved macronutrient metabolism, increased muscle mass, and decreased systemic inflammation. However, COPD patients vary widely in their responses to exercise interventions. Our understanding of the mechanisms which determine exercise capacity and the response to training is incomplete; our hypothesis is that epigenetic mechanisms such as DNA methylation are associated with both baseline exercise capacity and the systemic reprogramming that occurs with training. We propose to examine genome-wide DNA methylation patterns in blood from 2 existing VA-Boston based cohorts of COPD subjects with detailed, objective data on both exercise capacity and daily physical activity. Analysis of the first cohort, a cross-sectional cohort which includes subjects with a broad range of functional limitation, will help to establish the epigenetic determinants of baseline exercise capacity and physical activity (Objective 1). In the second cohort, we will determine longitudinal changes in methylation following an intervention to increase daily physical activity using paired samples collected before and after participation in the Every Step Counts trial (Objective 2). Finally, because traditional pulmonary rehabilitation programs typically involve higher intensity training than programs which target daily physical activity (such as the Every Step Counts program), we propose to collect de novo samples from COPD subjects referred to the VA Boston Pulmonary Rehabilitation program to characterize changes associated with higher intensity training (Objective 3). In addition to providing mechanistic insights on the benefits of exercise and increased physical activity, our proposal has the potential to assist in the development of algorithms for risk stratification and personalized treatment programs for COPD patients.

慢性阻塞性肺疾病（COPD）在美国退伍军人中非常普遍，这是一个重要的 发病率和死亡率的来源。 COPD患者经常降低运动能力（定义 作为患者执行工作的最大能力）和体育锻炼水平（一个经常用于的术语 描述患者的典型日常活动水平）。运动能力降低和体育锻炼是 与大量的临床结果相关，例如残疾，全因死亡率和医疗保健利用率 费率。重要的是，运动能力和体育锻炼代表了潜在的可修改风险因素 COPD。运动训练通常在结构化肺部康复的情况下进行 计划目前得到全球阻塞性肺部疾病（黄金）指南的认可 COPD非药物管理的重要组成部分，已被证明可以改善 症状和与健康相关的生活质量，同时减少医疗保健利用。除了正式 肺部康复，专注于改善每日体育锻炼的新型计划可能会提供 类似的好处。除了上述特定疾病的益处，运动训练和身体增加 活性也与全身变化有关，例如改善的大量营养素代谢， 增加肌肉质量，并减少全身炎症。但是，COPD患者的差异很大 他们对运动干预的反应。我们对决定运动的机制的理解 能力和对培训的反应是不完整的；我们的假设是表观遗传机制，例如 DNA甲基化与基线运动能力和全身重编程有关 发生在训练中。我们建议检查2种血液中全基因组DNA甲基化模式 现有的基于VA波士顿的COPD主题，具有详细的，客观的锻炼能力数据 和日常体育锻炼。对第一个队列的分析，这是一种横截面队列，包括具有的受试者 广泛的功能限制将有助于建立基线运动的表观遗传决定因素 能力和体育锻炼（目标1）。在第二个队列中，我们将确定 干预后甲基化使用收集的配对样品增加每日体育锻炼 参加每一步之前和之后都要计算试验（目标2）。最后，因为传统 肺康复计划通常涉及比针对每日针对的计划更高的强度训练 身体活动（例如每个步骤计数程序），我们建议从 COPD受试者称为VA波士顿肺康复计划，以表征变化 与更高强度训练相关（目标3）。除了提供机械见解 运动的好处和增加的体育锻炼，我们的建议有可能协助 开发针对COPD患者的风险分层和个性化治疗计划的算法。

项目成果

Long-term effects of web-based pedometer-mediated intervention on COPD exacerbations.

• DOI: 10.1016/j.rmed.2020.105878
• 发表时间: 2020-02
• 期刊: Respiratory medicine
• 影响因子: 4.3
• 作者: E. Wan;A. Kantorowski;Madeline Polak;Reema Kadri;C. Richardson;D. Gagnon;E. Garshick;M. Moy

Reply to Marruchella: Preserved Ratio Impaired Spirometry and Interstitial Lung Abnormalities in Smokers.

回复 Marruchella：吸烟者肺活量测定保留率受损和间质性肺异常。

• DOI: 10.1164/rccm.201901-0018le
• 发表时间: 2019
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7
• 作者: Wan,EmilyS;Silverman,EdwinK
• 通讯作者: Silverman,EdwinK

Molecular markers of aging, exercise capacity, & physical activity in COPD.

衰老、运动能力的分子标记，

• DOI: 10.1016/j.rmed.2021.106576
• 发表时间: 2021
• 期刊: Respiratory medicine
• 影响因子: 4.3
• 作者: Wan,EmilyS;Goldstein,RebekahL;Garshick,Eric;DeMeo,DawnL;Moy,MarilynL
• 通讯作者: Moy,MarilynL

Performance of bioelectrical impedance analysis compared to dual X-ray absorptiometry (DXA) in Veterans with COPD.

• DOI: 10.1038/s41598-022-05887-4
• 发表时间: 2022-02-04
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Cruz Rivera PN;Goldstein RL;Polak M;Lazzari AA;Moy ML;Wan ES
• 通讯作者: Wan ES

Examining genetic susceptibility in acute exacerbations of COPD.

检查 COPD 急性加重的遗传易感性。

• DOI: 10.1136/thoraxjnl-2017-211106
• 发表时间: 2018
• 期刊: Thorax
• 影响因子: 10
• 作者: Wan,EmilyS