Aerobic Capacity, Depression, & Inflammatory Responsivity in Cancer Survivors

有氧能力、抑郁、

基本信息

批准号：
8891741
负责人：
JANICE KIECOLT-GLASER
金额：
$ 63.11万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-16 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8891741
关键词：
Activities of Daily Living Address Aerobic Age Aging Anti-Inflammatory Agents Anti-inflammatory Attenuated Behavioral Biological Breast Cancer survivor Cancer Survivor Cardiovascular system Cessation of life Chronic Clinical Cognitive Cognitive deficits Cross-Over Studies Cross-Over Trials Data Depressed mood Disease Double-Blind Method Elderly Exercise Exercise stress test Fatigue Health Health Benefit Immune Individual Individual Differences Infection Inflammation Inflammatory Inflammatory Response Injury Kinetics Knowledge Lead Life Malignant Neoplasms Mental Depression Pain Partner in relationship Pattern Performance Peripheral Physical Capacity Physical Fitness Physical Function Physical activity Physically Handicapped Placebos Process Production Randomized Recording of previous events Risk Signal Transduction Stimulus System Time Tissues Typhoid Fever Typhoid Vaccine Vaccines Woman age effect age related behavioral response cancer therapy cytokine deconditioning depressive symptoms disability fitness high risk improved insight mortality negative mood novel older women premature primary outcome public health relevance response secondary outcome sedentary toll-like receptor 4 tumor growth vaccine response young woman

项目摘要

DESCRIPTION (provided by applicant): Cancer survivors' cardiorespiratory fitness often declines substantially during and following cancer treatment, and this pattern is alarming because inflammation is higher in sedentary than in active individuals. Indeed, when cardiorespiratory fitness is assessed objectively by maximal exercise testing, poorer physical fitness (VO2peak) is associated with higher inflammation. Chronic elevations in inflammation increase the risk for age- related diseases; the ability to limit initial inflammatory responses isan important homeostatic process. An immune challenge provides a useful paradigm for studying individual differences in inflammatory responses to infection or tissue injury. Accordingly, this project will use a typhoid vaccine as a peripheral immune stimulus to assess the magnitude and kinetics of a transient inflammatory response in breast cancer survivors. Inflammation-associated behavioral changes that have particular importance for breast cancer survivors will also be assessed--depressive symptoms, fatigue, pain, and cognitive problems. Our study addresses a novel question: does poorer cardiorespiratory fitness heighten the magnitude and duration of inflammatory responses to immune challenges, as well as magnifying maladaptive behavioral responses? Furthermore, biological and behavioral vulnerabilities intensify adverse responses to immune challenges. For example, both aging and depression enhance and prolong inflammatory responses to vaccines, and thus the ability of cardiorespiratory fitness to moderate age- and depression-related proinflammatory responses will also be assessed. This double-blind, randomized, crossover trial will evaluate inflammatory and behavioral responses to typhoid and placebo inoculations as a function of cardiorespiratory fitness, age, and depression in breast cancer survivors. The aims of the project are (1) to evaluate the relationships between cardiorespiratory fitness and inflammatory and behavioral responses (negative mood, fatigue, pain, and cognitive problems) to typhoid vaccine; (2) to determine the effects of age and depressive symptoms on inflammatory and behavioral responses to typhoid vaccine and placebo; and (3) to assess the ability of cardiorespiratory fitness to moderate age- and depression-related responses to typhoid vaccine. These questions are important because inflammation, a robust and reliable predictor of all-cause mortality in older adults, is one of the key candidate mechanisms for age-related decrements in physical function and disability. Individuals frequently encounter immune challenges in daily life, and the ability to minimize inflammatory responsiveness influences the total burden that infectious challenges or tissue injury place on an individual. Larger, more frequent, or more persistent inflammatory changes have negative consequences for health. If better cardiorespiratory fitness dampens or limits inflammatory responsiveness, then this study could demonstrate a new and novel mechanism through which regular exercise produces its substantial health benefits.

描述（由申请人提供）：癌症幸存者的心肺健康状况在癌症治疗期间和治疗后通常会大幅下降，这种模式令人担忧，因为久坐的人的炎症水平高于活跃的个体。事实上，当通过最大运动测试客观评估心肺健康状况时，较差的身体素质（摄氧量峰值）与较高的炎症水平有关，会增加患年龄相关疾病的风险；限制初始炎症反应的能力是一个重要的稳态过程。免疫挑战为研究感染或组织损伤的炎症反应的个体差异提供了有用的范例，因此，该项目将使用伤寒疫苗作为外周免疫刺激物来评估乳腺癌幸存者的短暂炎症反应的程度和动力学。 - 还将评估对乳腺癌幸存者特别重要的相关行为变化 - 抑郁症状、疲劳、疼痛和认知问题：我们的研究解决了一个新问题：较差的心肺健康是否会加剧炎症反应的程度和持续时间。此外，生物和行为脆弱性会加剧对免疫挑战的不良反应，例如，衰老和抑郁都会增强和延长对疫苗的炎症反应，从而增强和延长心肺健康的能力。 - 还将评估与抑郁症相关的促炎症反应，这项双盲、随机、交叉试验将评估伤寒和安慰剂接种的炎症和行为反应与心肺功能的关系。该项目的目的是 (1) 评估心肺健康与伤寒疫苗的炎症和行为反应（消极情绪、疲劳、疼痛和认知问题）之间的关系；）确定年龄和抑郁症状对伤寒疫苗和安慰剂的炎症和行为反应的影响；以及（3）评估心肺健康调节伤寒疫苗的年龄和抑郁相关反应的能力。很重要，因为炎症是老年人全因死亡率的有力且可靠的预测因素之一，与年龄相关的身体功能下降和残疾的关键候选机制是，个体在日常生活中经常遇到免疫挑战，而最大限度地减少炎症反应的能力会影响感染挑战或组织损伤给个体带来的更大、更频繁的总负担。如果更好的心肺健康能够抑制或限制炎症反应，那么这项研究可以证明一种新的机制，通过这种机制，定期锻炼可以产生巨大的健康益处。