This K-23 award will provide an opportunity for Dr. Watkins to develop as an independent scientific investigator in the field of clinical and translational research, investigating the risk factors, and potentially causal factors, which explain the relationship between blood transfusion and trauma-associated acute lung injury (ALI). This will be accomplished through an integrated curriculum consisting of coursework in epidemiology and biostatistics;intensive mentoring by local experts in the complications of severe trauma, ALI biology, and transfusion medicine;and practical experience in designing, conducting, and interpreting a clinical research project. Dr. Watkins will use this award to become an independently funded clinical investigator with skills in advanced multivariate statistical methods and in the design of clinical and transitional studies which include planned biologic sampling strategies necessary for biomarker discovery and future gene expression studies. Moreover, he will gain an ability to design and implement clinically focused projects which translate basic science advances into clinical practice, and also translate observed clinical associations into new basic science studies focusing on organ injury mechanisms. This will lead to a successful independent research career focused on understanding the clinical and biologic role of blood transfusion in the development of trauma-associated ALI and other trauma-related organ dysfunction. The primary scientific goal of this proposal is to determine the role of blood product storage time and cell-derived microparticles in the development of trauma-associated ALI. To achieve this goal Dr. Watkins will: I.) establish the relationship between the storage time of transfused red blood cells and the development of trauma-associated ALI in severely injured patients requiring transfusion, II.) compare the quantity of cellderived microparticles within donor blood that is transfused to patients who subsequently develop, versus do not develop, trauma-associated ALI, and III.) obtain blood samples from a well-defined, severely injured trauma patient phenotype and: A.) use these samples to determine the associations between circulating cellderived microparticles, transfusion, and trauma-associated ALI, and B.) establish an RNA repository from circulating leukocytes which will be archived for future studies aimed at identifying gene expression patterns associated with blood transfusion and with trauma-associated ALI.

Public Health Relevance

This project has important implications for those with severe trauma. The identification of potentially causal and modifiable factors important to the development of ALI could translate into novel biomarkers or new blood product storage, processing, or transfusion guidelines. The goal of the microparticle studies is to reveal novel mechanisms of disease, opening new avenues for basic study. Finally, the identification of modifiable factors showing promise in preventing trauma-associated ALI could be tested as interventions in future randomized clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
7K23GM086729-02
Application #
8054137
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Somers, Scott D
Project Start
2009-02-01
Project End
2014-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
2
Fiscal Year
2010
Total Cost
$122,040
Indirect Cost
Name
Puget Sound Blood Center
Department
Type
DUNS #
092881085
City
Seattle
State
WA
Country
United States
Zip Code
98104
Vande Vusse, Lisa K; Madtes, David K; Bolgiano, Douglas et al. (2016) The association between platelet transfusion and idiopathic pneumonia syndrome is unaffected by platelet product type. Transfusion 56:489-96
Peltan, Ithan D; Watkins, Timothy R (2016) The authors reply. Crit Care Med 44:e106-7
Peltan, Ithan D; Rowhani-Rahbar, Ali; Vande Vusse, Lisa K et al. (2016) Development and validation of a prehospital prediction model for acute traumatic coagulopathy. Crit Care 20:371
Vande Vusse, Lisa K; Caldwell, Ellen; Tran, Edward et al. (2015) The Epidemiology of Transfusion-related Acute Lung Injury Varies According to the Applied Definition of Lung Injury Onset Time. Ann Am Thorac Soc 12:1328-35
Peltan, Ithan D; Vande Vusse, Lisa K; Maier, Ronald V et al. (2015) An International Normalized Ratio-Based Definition of Acute Traumatic Coagulopathy Is Associated With Mortality, Venous Thromboembolism, and Multiple Organ Failure After Injury. Crit Care Med 43:1429-38
Vande Vusse, Lisa K; Madtes, David K; Guthrie, Katherine A et al. (2014) The association between red blood cell and platelet transfusion and subsequently developing idiopathic pneumonia syndrome after hematopoietic stem cell transplantation. Transfusion 54:1071-80
Cooke, Colin R; Watkins, Timothy R (2013) Variation in the incidence and timing of acute lung injury: the role of race. Chest 143:881-882
Parsons, Elizabeth C; Kross, Erin K; Ali, Naeem A et al. (2013) Red blood cell transfusion is associated with decreased in-hospital muscle strength among critically ill patients requiring mechanical ventilation. J Crit Care 28:1079-85
Watkins, Timothy R; Nathens, Avery B; Cooke, Colin R et al. (2012) Acute respiratory distress syndrome after trauma: development and validation of a predictive model. Crit Care Med 40:2295-303
Hayden, Shailaja J; Albert, Tyler J; Watkins, Timothy R et al. (2012) Anemia in critical illness: insights into etiology, consequences, and management. Am J Respir Crit Care Med 185:1049-57

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