Accelerated Biologic Aging and Risk for Sepsis and Organ Failure Following Trauma

加速生物衰老以及创伤后败血症和器官衰竭的风险

• 批准号: 8290454
• 负责人: ELIZABETH Grooms NESMITH
• 金额: $ 9.34万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8290454
• 关键词: Accident and Emergency department; Acute; Address; Admission activity; Adrenal Cortex Hormones; Adrenal Glands; Affect; African American; Aging; Autoimmune Process; Basic Science; Behavioral; Behavioral Mechanisms; Biological Markers; Blood Transfusion; Caucasians; Caucasoid Race; Cause of Death; Cell Death; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic stress; Clinical Sciences; Critical Care; Data; Demographic Factors; Development; Disease; Elderly; Equilibrium; Event; Fatal Outcome; Feedback; Functional disorder; Future; Genetic; Glucocorticoids; Goals; Hair; Hormones; Hospitals; Hour; Hydrocortisone; Immune System Diseases; Immune system; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Injury Severity Score; Intensive Care Units; Knowledge; Lead; Length of Stay; Life; Link; Malignant Neoplasms; Measures; Mission; Morbidity - disease rate; Mutation; National Institute of Nursing Research; Non-Steroidal Anti-Inflammatory Agents; Organ; Organ failure; Outcome; Participant; Pathway interactions; Patients; Persons; Physiological; Plasma; Population; Predisposing Factor; Predisposition; Pregnancy; Premature aging syndrome; Prevention; Psychoneuroimmunology; Race; Recruitment Activity; Reporting; Research; Research Proposals; Research Support; Research Training; Risk; Risk Factors; Schedule; Science; Sepsis; Socioeconomic Status; Spinal cord injury; Steroids; Stress; System; Telomerase; Time; Trauma; United States National Institutes of Health; Vulnerable Populations; aged; allostatic load; base; career; cytokine; disorder prevention; immune function; killings; lifestyle factors; low socioeconomic status; mortality; neutrophil; premature; prevent; primary outcome; public health relevance; response; salicylate; statistics; symposium

DESCRIPTION (provided by applicant): Guided by an adapted version of the Vulnerable Populations Conceptual Framework which incorporates concepts from Psychoneuroimmunology, this project will examine bio-behavioral mechanisms associated with chronic stress and accelerated biologic aging (i.e. premature cell death and system decline) which could adversely affect susceptibility to sepsis and organ failure following trauma (i.e., acute, life-threatening injuries). Trauma kills more than 13 million people annually. Sepsis and organ failure are the leading causes of in- hospital trauma deaths and are affected by baseline inflammation and poor inflammatory response, yet few data exist to explain differences in vulnerability to these deadly outcomes. Research has shown that African Americans (AAs) and persons of low socioeconomic status (SES) have nearly twice the rates of sepsis and organ dysfunction as Caucasians. Low SES has been associated with baseline inflammation, a finding related to organ dysfunction. Chronic stress may be a contributing factor. AAs and persons of low SES report chronic stress, which has been linked to accelerated biologic aging via telomerase activity. Declining levels of telomerase have also been associated with advanced age, a known risk factor for sepsis and organ failure. Chronic stress has been linked with physiologic "wear and tear" (i.e. allostatic load) on immune system function, resulting in changes similar that which are seen with advanced age. Thus, the specific aims of this project are that 1) accelerated biologic aging is a significant predisposing factor contributing to susceptibility to sepsis and organ failure following trauma and 2) chronic stress is a significant predisposing factor contributing to increased baseline inflammation and differences in the magnitude of the inflammatory response. Trauma patients who are 1) 18-44 years old; 2) have injury severity scores >15; and 3) times of <1 hour from injury to Emergency Department admission (n =300) will be recruited. Accelerated biologic aging will be operationally defined by low telomerase activity. Chronic stress will be operationally defined by high scores on the Life Events and Difficulties Schedule and high hair cortisol. Participants will be excluded for 1) blood transfusion or infection < 2 weeks prior to admission; 2) steroid, NSAID, or salicylate use for > 1 month prior to admission; 3) pre-existing organ disease; 4) cancer, autoimmune conditions, or pregnancy; 5) spinal cord injury; or missing data. Primary outcome variables are susceptibility to sepsis and organ failure, baseline inflammation status, and magnitude of the inflammatory response to trauma indicated by the 1) overall response and 2) peak magnitude of inflammatory cytokines and immature neutrophils in plasma from ED admission through ICU length of stay. Secondary variables will also be analyzed, including socio-demographic and lifestyle factors. Knowledge gained will inform future studies to prevent these often-fatal outcomes. This research is consistent with the National Institute of Nursing Research mission, which supports research that incorporates the best of clinical and basic science to develop unique approaches to disease prevention. PUBLIC HEALTH RELEVANCE: Trauma, defined as acute, life-threatening injuries, is the leading cause of death for individuals aged 18-44 years. Accelerated (i.e., premature) aging and chronic stress before trauma could explain why some individuals have poor outcomes in the intensive care unit after trauma, such as sepsis and organ failure. Information from this research will help us better understand why different populations of trauma patients have different outcomes, and could be used in future studies aimed at prevention.

DESCRIPTION (provided by applicant): Guided by an adapted version of the Vulnerable Populations Conceptual Framework which incorporates concepts from Psychoneuroimmunology, this project will examine bio-behavioral mechanisms associated with chronic stress and accelerated biologic aging (i.e. premature cell death and system decline) which could adversely affect susceptibility to sepsis and organ failure following trauma (i.e., acute, life-threatening受伤）。创伤每年杀死超过1300万人。败血症和器官衰竭是导致医院创伤死亡的主要原因，受基线炎症和炎症反应不良的影响，但很少有数据可以解释这些致命结果的脆弱性差异。研究表明，非洲裔美国人（AAS）和社会经济状况低下的人（SES）几乎是败血症和器官功能障碍的两倍。低SES与基线炎症有关，这是与器官功能障碍有关的发现。慢性压力可能是一个促成因素。 AAS和低SES的人报告了慢性应激，这与端粒酶活性与加速生物衰老有关。端粒酶水平下降也与高级年龄有关，这是败血症和器官衰竭的已知危险因素。慢性应激与免疫系统功能上的生理压力“磨损”（即同层负荷）有关，从而导致相似的变化与高龄相似。因此，该项目的具体目的是：1）加速生物学衰老是产生创伤后败血症和器官衰竭易感性的重要易感因素，而2）慢性应激是一种重要的倾向因子，这有助于增加碱基炎症和炎症反应的差异。 1）18-44岁的创伤患者； 2）受伤严重程度得分> 15； 3）从受伤到急诊科入场（n = 300）的时间<1小时。加速的生物衰老将由低端粒酶活性在操作上定义。慢性压力将在生命事件和困难时间表和高头发皮质醇上的高分在操作上定义。参与者将被排除在1）入院前<2周的输血或感染； 2）入院前> 1个月的类固醇，NSAID或水杨酸酯使用； 3）预先存在的器官疾病； 4）癌症，自身免疫性状况或怀孕； 5）脊髓损伤；或缺少数据。主要结果变量是对败血症和器官衰竭，基线炎症状态的敏感性，以及对1）总反应和2）炎症性细胞因子的峰值和未成熟嗜中性粒细胞的峰值的炎症反应的幅度，而在ICU到ICU长度的峰值。还将分析次要变量，包括社会人口统计学和生活方式因素。获得的知识将为未来的研究提供信息，以防止这些经常致力的结果。这项研究与国家护理研究所的任务一致，该研究所支持纳入最佳临床和基础科学的研究，以开发独特的预防疾病方法。 公共卫生相关性：被定义为急性，威胁生命的伤害的创伤是18-44岁的个人的主要死亡原因。创伤之前加速（即早产）衰老和慢性压力可以解释为什么有些人在创伤后在重症监护病房的结果很差，例如败血症和器官衰竭。这项研究的信息将有助于我们更好地理解为什么不同的创伤患者群体会有不同的结果，并且可以在旨在预防的未来研究中使用。