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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

基本信息

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
项目类别：
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

项目摘要

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.

描述（由申请人提供）：由改编版的脆弱人群概念框架（其中包含来自心理神经免疫学的概念）指导，该项目将研究与慢性应激和加速生物衰老（即细胞过早死亡和系统衰退）相关的生物行为机制，这些机制可能对创伤后败血症和器官衰竭的易感性产生不利影响（即，急性、危及生命的损伤）。创伤每年造成1300多万人死亡。脓毒症和器官衰竭是院内创伤死亡的主要原因，并受到基线炎症和不良炎症反应的影响，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）和社会经济地位低的人（SES）的败血症和器官功能障碍的发病率几乎是白人的两倍。低SES与基线炎症相关，这是一项与器官功能障碍相关的发现。慢性压力可能是一个促成因素。AA和低SES的人报告慢性压力，这与通过端粒酶活性加速生物衰老有关。端粒酶水平的下降也与高龄有关，这是脓毒症和器官衰竭的已知危险因素。慢性压力与免疫系统功能的生理“磨损”（即非稳态负荷）有关，导致类似于老年人所见的变化。因此，本项目的具体目标是：1）加速生物老化是导致创伤后脓毒症和器官衰竭易感性的重要诱发因素，2）慢性应激是导致基线炎症增加和炎症反应程度差异的重要诱发因素。将招募1）18-44岁; 2）损伤严重度评分>15;和3）从损伤到急诊入院时间<1小时的创伤患者（n =300）。加速的生物老化将可操作地定义为低端粒酶活性。慢性压力在操作上将被定义为生活事件和困难量表的高分和高头发皮质醇。参与者将因以下情况而被排除：1）入院前输血或感染< 2周; 2）入院前使用类固醇、NSAID或水杨酸盐> 1个月; 3）预先存在的器官疾病; 4）癌症、自身免疫性疾病或妊娠; 5）脊髓损伤;或缺失数据。主要结果变量是脓毒症和器官衰竭的易感性、基线炎症状态和创伤炎症反应的程度，其由1）总体反应和2）从艾德入院到ICU住院时间的血浆中炎性细胞因子和未成熟中性粒细胞的峰值程度指示。还将分析次要变量，包括社会人口统计学和生活方式因素。所获得的知识将为未来的研究提供信息，以防止这些往往致命的结果。这项研究与国家护理研究所的使命是一致的，该研究支持将最好的临床和基础科学结合起来，开发独特的疾病预防方法的研究。公共卫生相关性：创伤被定义为急性、危及生命的伤害，是18-44岁人群死亡的主要原因。加速（即，过早）衰老和创伤前的慢性压力可以解释为什么有些人在创伤后的重症监护室中结果不佳，如败血症和器官衰竭。这项研究的信息将帮助我们更好地理解为什么不同人群的创伤患者有不同的结果，并可用于未来的预防研究。