DAMP-Mediated Innate Immune Failure and Pneumonia After Trauma - the Harvard-Longwood (HALO) Campus Area Consortium

Summary

The mortality burden of trauma in the United States is substantial, and is currently the leading cause of death in warfare and in civilians below age 45. Infection and sepsis are leading causes of morbidity and death in early survivors. Pneumonia (PNA) occurs in 17-36% of ventilated trauma patients; far more than non-trauma patients. The long held dogmatic notion of a mechanical predisposition to development of pneumonia in trauma has lacked robust support. However, there is evidence of the innate immune response to injury plays a major role in increasing susceptibility to infection.

This application is for support of a Focused Program Award addressing the role that "danger signaling" due to "danger associated molecular patterns" (or DAMPs) derived from somatic tissue injuries play in altering innate immune signaling in the lung in ways that predisposes to PNA. This innate immune response plays a pivotal role in the development and progression of lung inflammation. The organization of the Focused Program Award is into six Projects with collaborators from the Departments of Surgery, Medicine and Anesthesiology at Beth Israel Deaconess Medical Center; the Department of Surgery at Brigham and Women's Hospital and the Departments of Biology and Biological Engineering at Massachusetts Institute of Technology.

The human subjects interaction portion of this project is covered in the Human Subjects \& Samples Project of the Award, although the information and tissues obtained from this Project will be shared with the other Projects, and the activities planned for those Projects are outlined in this application.

Conditions

• Respiratory Failure

Interventions

OTHER

Normoxia with Normocarbia

PaO2 \< 100 (FiO2 \>= 21%) PaCO2 of 30-40

OTHER

Normoxia with Hypercarbia

PaO2 \< 100 (FiO2 \>= 21%) PaCO2 of 50-60

OTHER

Hyperoxia with Normocarbia

PaO2 \> 250 (FiO2 \>= 70%) PaCO2 of 30-40

OTHER

Hyperoxia with Hypercarbia

PaO2 \> 250 (FiO2 \>= 70%) PaCO2 of 50-60

Sponsors & Collaborators

• United States Department of Defense

  collaborator FED

• Beth Israel Deaconess Medical Center

  lead OTHER

Principal Investigators

• Daniel Talmor, MD MPH · Beth Israel Deaconess Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-11-15

Primary Completion

2020-03-15

Completion

2021-10-01

Countries

• United States

Study Locations