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: 9543938
• 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 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9543938
• 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; predictive modeling; prognostic; programs; tool; von Willebrand Factor; 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; predictive modeling; prognostic; programs; 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.

烧伤损伤和危险饮酒是急性呼吸道发展的单独风险因素 遇险综合征（ARDS），这是呼吸衰竭的常见原因。 ARDS是 肺免疫功能障碍，其中四分之一以上的患者会发展为多器官衰竭并死亡。 临床研究已经在非燃烧的ARDS患者中建立了关键的预后血浆生物标志物。动物 实验清楚地表明，BAC升高会加剧烧伤损伤的有害影响 肺和全身先天免疫反应。不幸的是，升高的BAC或危险的作用 尚未评估燃烧患者的ARDS开发的酒精使用。风险临床研究 需要针对预防和治疗的患者的烧伤患者的ARDS发育预测 试验。应用中介分析，一种新颖而健壮的统计工具，并验证新的直接酒精 生物标志物是本应用程序中的方法，可以更好地检查ARDS上的危险酒精使用的关联 发展。我的两个核心假设是，燃烧患者的危险饮酒与 ARDS的发展以及结合临床和生物学因素可以准确预测 在烧伤患者中进行弧形。因此，研究的具体目的是（1）确定发展的风险 使用中介分析与不同水平的BAC相关的ARD； （2）派生和内部 使用燃烧患者的临床风险因素和生物标志物来验证ARDS风险预测模型； （3） 与审计相比，识别并验证了Peth水平的临界值。 拟议的5年研究培训将在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。我研究的一个重要方面是继续使用生物标志物作为 连接传统分子和流行病学研究的工具，并了解酒精在 重症患者。这项翻译研究建议使我能够为生物标志物开发新的用途 酒精并在临床环境中燃烧并应用它们，以潜在地识别ARDS的危险因素。长 因此，当前建议的一项目标是为目标人群的未来临床试验设计。 酒精和炎症专家Kovacs博士的会议，库珀博士，专家 翻译研究和分子流行病学，最终将使我成为一名独立的临床医生 科学家。我的酒精流行病学专家咨询团队，酒精生物标志物和ARDS将支持我 短期和长期目标。酒精研究的协作和跨学科环境 芝加哥洛约拉大学的计划与燃烧和冲击创伤研究所，最大的 中西部的全州燃烧转介中心是该提议的理想选择。工作的影响 应用将使临床医生能够（1）确定烧伤患者的危险酒精使用并量化 与Ards的关联； （2）确定烧伤患者有ARDS发育的风险。这些数据可以 在目标人群中告知未来临床试验的设计。