Investigating Correlates and Therapeutics of Fatigue in Cancer Patients

研究癌症患者疲劳的相关性和治疗方法

• 批准号: 10013012
• 负责人: Leorey Saligan
• 金额: $ 171.14万
• 依托单位: NATIONAL INSTITUTE OF NURSING RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10013012
• 关键词: Action Potentials; Affective; Alcohol consumption; Animals; Anxiety; Behavioral; Biological Markers; Blood specimen; Cancer Fatigue; Cancer Patient; Cardiovascular Physiology; Chronic Disease; Clinic; Clinical Research; Cognitive; Communities; Coupling; Data; Dimensions; Disease; Emotional; Energy Metabolism; Enrollment; Etiology; Exertion; Failure; Fatigue; Functional disorder; Gene Expression; Glutamates; Glycolysis; IL8 gene; Immunotherapy; Impairment; In Vitro; Individual; Inflammation; Inflammatory; Insulin-Like Growth Factor I; Interleukin-6; Investigation; Laboratories; Life Experience; Literature; Longitudinal Studies; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Mental Depression; Molecular; Molecular Genetics; Muscle; Muscle Fibers; National Cancer Institute; Neuraxis; Observational Study; Oxygen Consumption; Pain; Participant; Patient Care; Patient Self-Report; Patients; Performance at work; Peripheral; Personal Satisfaction; Physiological; Primary Health Care; Psyche structure; Psychosocial Factor; Research; Rest; Risk; Risk Factors; Role; Sensory; Serotonergic System; Skeletal Muscle; Symptoms; TNF gene; Therapeutic; Time; Tissue Sample; Tobacco use; United States National Institutes of Health; Validation; base; cancer therapy; chemotherapy; cognitive function; cost; cytokine; diet and exercise; disabling symptom; economic outcome; experience; experimental study; health economics; health related quality of life; hormone therapy; lifestyle factors; multidisciplinary; muscle strength; negative affect; neural stimulation; peripheral blood; prospective; receptor; recruit; relating to nervous system

Fatigue is a multidimensional symptom that impacts 38% of community-based individuals and 42% of primary care patients. It is one of the most common and most debilitating symptoms in chronic illness and in cancer. It has significant repercussions on both direct and indirect health economic outcomes, costing an estimated annual lost productive time of US$330 million mostly due to reduced work performance. In cancer, fatigue had the greatest negative impact on daily activity, physical well-being/function, and relationships with significant others. Fatigue is described as a persistent, subjective sense of tiredness that interferes with usual functioning. It can be distinguished from normal everyday tiredness, because it is more frequent, unrelenting, unpredictable, and unresolved by rest. Fatigue may be influenced by a combination of physiological factors (e.g., inflammation or central nervous system dysfunction), psychosocial factors (e.g., depression or anxiety), and lifestyle factors (e.g., diet, exercise, alcohol use, tobacco use, or social role). Fatigue also co-occurs with other symptoms (e.g., pain, depression) contributing to symptom burden, which negatively affects health-related quality of life of patients. The etiology of fatigue is unknown, but it is believed to have central and peripheral components. Central fatigue is hypothesized to result from a decrease in central nervous system drive brought about by serotonergic pathways limiting muscle fiber recruitment during exertion reducing muscle glycolysis, oxygen consumption, and cardiovascular function. Peripheral fatigue is the inability of a particular muscle to perform a task even with an increased neural drive. This is thought to be caused by an action potential failure, cross-bridge formation impairment, or excitation contraction coupling failure amidst increased neural stimulation. The interplay between central and peripheral types of fatigue remains unclear although an increasing body of literature has indicated a potential interaction of both mechanisms. The research team continues to enroll participants for their studies that investigate the molecular-genetic correlates, as well as possible therapeutics of cancer-related fatigue. The group recently made significant discoveries related to the activation of glutamatergic receptors associated with cancer therapy that trigger inflammation that may explain the fatigue experience related to cancer therapy. Further validation is being conducted through clinical studies, animal projects and in vitro experiments. The PI is working closely with collaborators from the Multidisciplinary Prostate Cancer Clinics of the National Cancer Institute to continue to recruit study participants. The study team is also collaborating with several NIH core laboratories to further their investigations.

疲劳是一种多维症状，影响38%的社区个体和42%的初级保健患者。它是慢性病和癌症中最常见和最使人衰弱的症状之一。它对直接和间接的卫生经济结果产生重大影响，主要由于工作绩效下降，估计每年造成3.3亿美元的生产时间损失。在癌症中，疲劳对日常活动、身体健康/功能以及与重要他人的关系有最大的负面影响。疲劳被描述为一种持续的、主观的疲倦感，干扰了正常的功能。它可以区别于正常的日常疲劳，因为它是更频繁的，无情的，不可预测的，并解决休息。疲劳可能受到生理因素（如炎症或中枢神经系统功能障碍）、心理社会因素（如抑郁或焦虑）和生活方式因素（如饮食、运动、饮酒、吸烟或社会角色）的综合影响。疲劳还与其他症状（如疼痛、抑郁）同时发生，造成症状负担，对患者与健康相关的生活质量产生负面影响。疲劳的病因尚不清楚，但它被认为有中枢和外周成分。中枢性疲劳被认为是由于5 -羟色胺能通路导致的中枢神经系统驱动力下降，限制了运动过程中肌纤维的补充，减少了肌肉糖酵解、耗氧量和心血管功能。外周疲劳是指即使神经动力增强，特定肌肉也无法完成任务。这被认为是由动作电位失效、交叉桥形成损伤或神经刺激增加时兴奋收缩耦合失效引起的。中枢性和外周性疲劳之间的相互作用尚不清楚，尽管越来越多的文献表明这两种机制之间存在潜在的相互作用。