Alcohol, Burn-Injury, and Acute Respiratory Distress Syndrome

酒精、烧伤和急性呼吸窘迫综合征

• 批准号: 9765117
• 负责人: Majid Afshar
• 金额: $ 19.14万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765117
• 关键词: Adult Respiratory Distress Syndrome; Advisory Committees; Alanine Transaminase; Alcohol abuse; Alcohols; Animal Experiments; Animals; Area; Aspartate Transaminase; Biological Factors; Biological Markers; Blood alcohol level measurement; Body Surface Area; Burn injury; Cell Adhesion Molecules; Cessation of life; Chicago; Clinical; Clinical Research; Clinical Trials; Critical Care; Critical Illness; Data; Data Set; Development; Diagnostic; Dose; Epidemiology; Future; Gamma-glutamyl transferase; Goals; Immune System Diseases; Immune response; Immunologics; Inflammation; Inhalation; Injury; Innate Immune Response; Interleukin-6; Link; Lung; Measures; Mediation; Mentorship; Methods; Midwestern United States; Molecular; Molecular Epidemiology; Multiple Organ Failure; Organ; Outcome; Outcome Study; Pathogenesis; Patients; Phenotype; Plasma; Population; Prevention trial; Proxy; Pulmonary Surfactant-Associated Protein D; Reference Standards; Registries; Research; Research Institute; Research Personnel; Research Proposals; Research Training; Respiratory Failure; Risk; Risk Factors; Role; Scientist; Severities; Shock; TNF gene; Target Populations; Testing; Therapeutic Trials; Translational Research; Trauma Research; Trauma patient; Universities; Work; alcohol abuse therapy; alcohol effect; alcohol epidemiology; alcohol exposure; alcohol research; alcohol use disorder; biomarker development; biomedical referral center; carbohydrate-deficient transferrin; clinical risk; collaborative environment; design; effective therapy; epidemiology study; indexing; injured; insight; instrument; mean corpuscular volume observed; novel; outcome prediction; phosphatidylethanol; predictive marker; prognostic; programs; risk prediction model; tool; von Willebrand Factor

Burn injury and hazardous alcohol use are separate risk factors for development of the acute respiratory distress syndrome (ARDS), a common cause of respiratory failure. ARDS is an important manifestation of pulmonary immune dysfunction, and over a quarter of these patients progress to multiple organ failure and die. Clinical studies have established key prognostic plasma biomarkers in non-burn patients with ARDS. Animal experiments clearly demonstrate elevated BAC exacerbates the harmful effects of burn injury via the pulmonary and systemic innate immune response. Unfortunately, the role of elevated BAC or of hazardous alcohol use on the development of ARDS in burn patients has not been evaluated. Clinical studies on risk prediction for ARDS development in burn patients are needed to target patients for prevention and therapeutic trials. Applying mediation analysis, a novel and robust statistical tool, and validating a new direct alcohol biomarker are methods in this application to better examine the association of hazardous alcohol use on ARDS development. My two central hypotheses are that hazardous alcohol use in burn patients is associated with development of ARDS and that combining clinical and biological factors can accurately predict development of ARDS in burn patients. Therefore, the specific aims of the study are to (1) identify the risk for development of ARDS associated with different levels of BAC using mediation analysis; (2) derive and internally validate an ARDS risk prediction model using clinical risk factors and biomarkers in burn patients; (3) identify and validate a cutoff for PEth level for hazardous alcohol use in comparison to the AUDIT. The proposed 5-year research training will provide needed new information in a relatively unexplored area of alcohol and critical care research. One important facet of my research is to continue using the biomarker as a tool to link traditional molecular and epidemiological research and understand alcohol's immunologic role in the critically ill patient. This translational research proposal allows me to develop new uses for biomarkers in alcohol and burn and apply them in a clinical setting to potentially identify risk factors for ARDS. The The long term goal of current proposal therefore is to inform the design of future clinical trials in a targeted population. Co-mentorship from Dr. Kovacs, an expert in alcohol and inflammation, and Dr. Cooper, an expert in translation research and molecular epidemiology, will ultimately enable me to become an independent clinician scientist. My advisory team of experts in alcohol epidemiology, alcohol biomarkers, and ARDS will support my short- and long-term goals. The collaborative and interdisciplinary environment of the Alcohol Research Program and Burn and Shock Trauma Research Institute at Loyola University Chicago, one of the largest statewide burn referral centers in the Midwest, are ideal for this proposal. The impact of the work from this application will enable clinicians to (1) identify hazardous alcohol use in burn patients and quantify its association with ARDS; (2) identify burn patients at risk for development of ARDS. These data could then inform the design of future clinical trials in a targeted population.

烧伤和危险的酒精使用是急性呼吸道疾病发生的独立危险因素。 急性呼吸窘迫综合征（ARDS）是呼吸衰竭的常见原因。急性呼吸窘迫综合征（ARDS）是 肺免疫功能障碍，超过四分之一的患者进展为多器官衰竭并死亡。 临床研究已经确定了非烧伤ARDS患者的关键预后血浆生物标志物。动物 实验清楚地表明，升高的BAC通过以下途径加剧了烧伤的有害影响： 肺和全身先天免疫反应。不幸的是，BAC升高或有害的 酒精使用对烧伤患者发生ARDS的影响尚未得到评估。风险的临床研究 需要预测烧伤患者的ARDS发展，以针对患者进行预防和治疗 审判应用中介分析，一种新的和强大的统计工具，并验证一种新的直接醇 生物标志物是本申请中更好地检查危险酒精使用与ARDS之间关系的方法 发展我的两个中心假设是，烧伤患者危险的酒精使用与以下因素有关： 结合临床和生物学因素可以准确预测ARDS的发展， 烧伤病人的ARDS因此，本研究的具体目标是：（1）识别发展风险 使用中介分析与不同水平的BAC相关的ARDS;（2）衍生和内部 使用烧伤患者的临床危险因素和生物标志物验证ARDS风险预测模型;（3） 与AUDIT相比，确定并验证有害酒精使用的PEth水平的截止值。 拟议的5年研究培训将在一个相对未开发的领域提供所需的新信息， 酒精和重症监护研究我的研究的一个重要方面是继续使用生物标志物作为一种 这是一种将传统的分子和流行病学研究联系起来的工具， 危重病人这项转化研究提案使我能够开发生物标志物的新用途， 酒精和烧伤，并将其应用于临床环境中，以确定潜在的危险因素为ARDS。The Long 因此，当前提案的长期目标是为目标人群中未来临床试验的设计提供信息。 Kovacs博士是酒精和炎症方面的专家，库珀博士是 翻译研究和分子流行病学，将最终使我成为一个独立的临床医生 科学家我的酒精流行病学、酒精生物标志物和ARDS专家顾问团队将支持我的研究。 短期和长期目标。酒精研究的协作和跨学科环境 计划和烧伤和休克创伤研究所在洛约拉大学芝加哥，其中一个最大的 中西部的全州烧伤转诊中心是这个建议的理想选择。这项工作的影响 该应用程序将使临床医生能够（1）识别烧伤患者的危险酒精使用，并量化其 与ARDS的相关性;（2）识别有发展为ARDS风险的烧伤患者。这些数据可以 为未来在目标人群中进行临床试验的设计提供信息。