Trauma-Associated Acute Respiratory Distress Syndrome: Identifying Immunologic Risk with Cytometry Time-of-Flight
Abstract
Problem: Acute respiratory distress syndrome (ARDS) is an inflammatory condition whereby the lungs become filled with fluid in response to severe illness, including severe trauma. The accumulation of fluid into the lungs leads to a decrease in oxygen levels in the patient, and the overall mortality rate for patients with this condition is around 33%. Roughly 16%-34% of severely injured trauma patients develop ARDS. Mortality rates are significantly higher for severely injured combat troops who develop ARDS compared with those who do not develop ARDS, and operational resource utilization is significant higher in these patients as well. It is unknown why some severely injured patients develop ARDS versus those who do not. Moreover, there are currently no therapies specifically directed at ARDS that have been shown to improve outcomes. Previous research has demonstrated that immune cells in both the blood and lung play an extremely important role in the development of ARDS. However, attempts to identify which immune cells are injurious or beneficial have been unsuccessful. Technical limitations have been partly to blame, given that until a few years ago researchers could only examine 8-10 proteins on an individual cell at a given time. New technology (cytometry time-of-flight, or CyTOF) allows us to now look at 40 to hundreds of proteins on a single cell at a given time, permitting us to very accurately define specific cells and their functions. Research Question: Are there specific immune cells in the blood and lung of severely injured trauma patients that are associated with the development of ARDS and duration of trauma-associated respiratory failure?Proposal: We propose to collect lung and blood immune cells from severely injured trauma patients at the time of hospital arrival. We will then analyze those immune cells with CyTOF and test for associations between our CyTOF findings and outcomes such as development of ARDS and survival. Innovation: The most innovative aspect of this project proposal is that we are proposing the use of a new technology – CyTOF – for the analysis of blood and lung immune cells in severely injured patients. CyTOF has been used in immunology and oncology, and it is revolutionizing those fields because it provides exponentially more granular information about cells than conventional tools (flow cytometry). However, it has not been used in the setting of severe trauma or trauma-associated ARDS. We hypothesize that this novel technology will allow us to identify new immune cells and functions that play a key role in the development and severity of trauma-associated ARDS. Impact: The identification of immune cells that are associated with the development of ARDS and survival would lead to multiple novel areas of investigation in both basic science and clinical research. From a basic science standpoint, the immune cells and molecular processes that are implicated with ARDS would be investigated in animal models and lab assays. This could lead to the development of new drugs and therapies to prevent or treat ARDS. From a clinical standpoint, immune cells and molecular processes that are implicated with ARDS would represent a new biomarker that could help physicians predict which patients are at highest risk for developing ARDS. This could help with triage and resource allocation in operational environments, and well as early medical interventions to try and limited further lung damage in these patients. Finally, the discovery of a novel biomarker could be used in future clinical trials to help identify patient populations that might better respond to targeted therapy (personalized medicine).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910218
Entities
People
- Mark Wurfel
Organizations
- United States Army
- University of Washington