DAMP-Mediated Innate Immune Failure and Pneumonia after Trauma
Abstract
Trauma is the most common cause of death in combatants and is the most common civilian cause of death under age. Most intensive care unit (ICU) deaths and prolonged sickness after injury are due to infection and organ failure with pneumonia (PNA) occurring in 17%-36% of injured ICU patients. This is far more than in non-trauma ICU patients, so there is something fundamental about injury that makes injured patients susceptible to infection. It is well accepted, for instance, that when elderly patients fall and break a hip, they die of pneumonia and not their injury. The fundamental problem that our program addresses is the need to discover the biologic connection between injury and infection and identify potential solution that prevent and treat these infections that sicken and kill wounded Warfighters and civilians. Since pneumonia is the most common infection in severe trauma, the first designated Peer Reviewed Medical Research Program (PRMRP) topic area that our program addresses is Respiratory Health. Since we live in an era of increasing antibiotic-resistant bacteria, the second PRMRP topic we cover is the reduction of Healthcare Acquired Infections (HAI). HAI occur in patients who are very sick and especially those that have been treated with antibiotics. The bacteria residing in healthcare facilities have typically evolved to be resistant to multiple antibiotics. Thus, when a severely injured Warrior develops an infection while under care in combat support facilities, that infection is often caused by such a resistant bacteria. Plus, in addition to pneumonia, injured Warfighters typically have other wounds that are at risk for infection and may require antibiotic use. So their wounds are also at high risk for developing HAI caused by antibiotic-resistant bacteria. By determining why patients are biologically susceptible to infection to begin with, we expect to be able to devise strategies that prevent susceptibility. Therefore, patients should get fewer infections, require fewer antibiotics, and develop fewer resistant HAI. The third PRMRP topic our program will investigate is Integrative Medicine. Our multidisciplinary approach assembles and assimilates authorities and scientific approaches that all have a fundamental interest in understanding why patients develop infections, but typically operate in different arenas. For example, we believe that the ability of immune cells in the lung to fight infection is altered in part by the amount of oxygen the injured patient is breathing. This simple problem has never been addressed because the clinical scientists who manage ICUs rarely interact with basic scientists who study immunity. Our methods focus on state-of-the-art "big data" computational modeling and analyses, which can recognize relationships between scientific and clinical data parameters that are not normally evaluated in such an integrated, cohesive fashion. This approach will lead to important new discoveries and medical therapies benefitting Wounded Warriors. In summary, we anticipate that in the course of this program, we will greatly advance the understanding of why Warriors become susceptible to infections after traumatic injury. This new knowledge will generate a pipeline of novel treatments aimed at improving the prevention and treatment of post-traumatic infection, thus improving the outcomes of injury in theater.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610464
Entities
People
- Carl J. Hauser
Organizations
- Beth Israel Deaconess Medical Center
- United States Army