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CHANGE OF GRANTEE INSTITUTION 1 K23 AA024503 Alcohol, Burn-Injury, and Acute Respiratory Distress Syndrome

受资助者机构变更 1 K23 AA024503 酒精、烧伤和急性呼吸窘迫综合征

基本信息

批准号：
10204442
负责人：
Majid Afshar
金额：
$ 19.14万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-23 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10204442
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 Institution 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 insight instrument mean corpuscular volume observed novel outcome prediction phosphatidylethanol predictive marker prognostic programs risk prediction model tool von Willebrand Factor

项目摘要

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.

烧伤和危险饮酒是发展为急性呼吸道疾病的独立危险因素。窘迫综合征(ARDS)，呼吸衰竭的常见原因。ARDS是一种重要的肺部免疫功能障碍，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患者的关键血浆生物标志物。动物实验清楚地表明，BAC升高通过以下途径加重烧伤的有害影响肺和全身的先天免疫反应。不幸的是，升高的BAC或危险的酒精使用对烧伤患者发生ARDS的影响尚未得到评估。关于风险的临床研究需要对烧伤患者ARDS的发展进行预测，以便有针对性地预防和治疗审判。应用中介分析这一新颖而稳健的统计工具，验证了一种新的直接酒精生物标记物是本应用中更好地检查ARDS中危险酒精使用的关联性的方法发展。我的两个中心假设是烧伤患者使用有害酒精与 ARDS的发展及结合临床和生物因素可准确预测烧伤患者的不良反应。因此，这项研究的具体目的是(1)确定发展的风险使用中介分析与不同级别的BAC相关联的ARDS；(2)派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) 与审计相比，确定并验证有害酒精使用的PEH水平的截止水平。拟议的为期5年的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与重症监护研究。我研究的一个重要方面是继续使用生物标记物作为将传统的分子和流行病学研究联系起来并了解酒精在疾病中的免疫学作用的工具危重病人。这项转化性研究计划使我能够在酒精和烧伤，并将其应用于临床环境中，以潜在地识别ARDS的风险因素。The Long The Long 因此，当前提案的长期目标是在目标人群中为未来临床试验的设计提供信息。来自酒精和炎症专家科瓦奇博士和库珀博士的共同指导，库珀博士是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、酒精生物标记物和ARDS专家顾问团队将支持我的短期和长期目标。酒精研究的协作和跨学科环境计划与烧伤和休克创伤研究所在芝加哥洛约拉大学，最大的之一位于中西部的全州范围内的烧伤转介中心是这项提议的理想选择。这项工作的影响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)确定烧伤患者发生ARDS的风险。然后这些数据就可以告知未来在目标人群中进行临床试验的设计。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Computable Phenotype for Acute Respiratory Distress Syndrome Using Natural Language Processing and Machine Learning.

使用自然语言处理和机器学习的急性呼吸窘迫综合征的可计算表型。

DOI：
发表时间：
2018
期刊：
AMIA ... Annual Symposium proceedings. AMIA Symposium
影响因子：
0
作者：
Afshar,Majid;Joyce,Cara;Oakey,Anthony;Formanek,Perry;Yang,Philip;Churpek,MatthewM;Cooper,RichardS;Zelisko,Susan;Price,Ron;Dligach,Dmitriy
通讯作者：
Dligach,Dmitriy

Helping Patients With ESRD and Earlier Stages of CKD to Quit Smoking.

DOI：
10.1053/j.ajkd.2018.01.057
发表时间：
2018-08
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
0
作者：
Formanek P;Salisbury-Afshar E;Afshar M
通讯作者：
Afshar M

Effects of binge alcohol consumption on sleep and inflammation in healthy volunteers.

酗酒对健康志愿者睡眠和炎症的影响。

DOI：
10.1177/0300060518782020
发表时间：
2018
期刊：
The Journal of international medical research
影响因子：
0
作者：
Wilkinson,AmandaN;Afshar,Majid;Ali,Osman;Bhatti,Waqas;Hasday,JeffreyD;Netzer,Giora;Verceles,AvelinoC
通讯作者：
Verceles,AvelinoC

Pre-training phenotyping classifiers.

训练前表型分类器。