Aerobic Capacity, Depression, & Inflammatory Responsivity in Cancer Survivors

 描述（由申请人提供）：癌症幸存者的心肺适应性在癌症治疗期间和之后经常大幅下降，这种模式令人担忧，因为久坐的人比活跃的人炎症更高。事实上，当通过最大运动测试客观评估心肺适能时，较差的体能（VO 2 peak）与较高的炎症相关。炎症的慢性升高增加了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。免疫激发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，以评估乳腺癌幸存者短暂炎症反应的程度和动力学。对乳腺癌幸存者特别重要的炎症相关行为变化也将被评估-抑郁症状，疲劳，疼痛和认知问题。我们的研究解决了一个新的问题：较差的心肺适应性是否会增加对免疫挑战的炎症反应的幅度和持续时间，以及放大适应不良的行为反应？此外，生物和行为脆弱性加剧了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，因此也将评估心肺适应性对中度年龄和抑郁相关促炎反应的能力。这项双盲、随机、交叉试验将评估乳腺癌幸存者对伤寒和安慰剂接种的炎症和行为反应，作为心肺功能、年龄和抑郁的函数。本研究的目的是：（1）评估心肺适能与炎症反应和行为反应之间的关系（2）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）评估心肺适应性对减轻年龄和抑郁相关的伤寒疫苗反应的能力。这些问题很重要，因为炎症是老年人全因死亡率的可靠预测因素之一， 与年龄相关的身体功能和残疾衰退的关键候选机制。个体在日常生活中经常遇到免疫挑战，并且使炎症反应最小化的能力影响感染挑战或组织损伤对个体造成的总负担。更大、更频繁或更持久的炎症变化对健康有负面影响。如果更好的心肺功能可以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，定期锻炼可以产生实质性的健康益处。

 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.