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.
I anticipate that the research proposed will provide novel and critically important insights into the risk from hazardous alcohol use and biomarkers on the development of the acute respiratory distress syndrome (ARDS) in burn-injured patients. This understanding will enable clinicians and researchers to (1) gain a better understanding of the phenotype of burn- ARDS and identifying hazardous alcohol users in the burn population; (2) develop a risk prediction model to identify important clinical risk factors and biomarkers for the development of ARDS in burn patients; (3) provide new avenues for developing effective treatment of alcohol- induced organ damage. Novel methods proposed in this application will also help advance the epidemiology and design of clinical studies in burn and alcohol research.
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