Research Project
10269671
PROJECT SUMMARY_CORE A Recovery from viral pneumonia is a clinically important yet understudied process. Severe viral pneumonia due to influenza A virus (IAV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), damages the lower respiratory tract to cause acute respiratory distress syndrome (ARDS). While acute hypoxemic respiratory failure is a defining clinical feature in patients with ARDS, advances in supportive care allow most patients to survive the hypoxemic phase of their illness. As a result, the vast majority of patients with ARDS die from multiple organ dysfunction, including persistent respiratory failure, days to weeks after the initial infection. Other than avoidance of additional lung injury, via low tidal volume ventilation and a handful of other supportive therapies, there are no specific therapies for patients with viral pneumonia/ARDS. A central hypothesis of this PPG is that the persistence of respiratory failure and the development of multiple organ dysfunction in patients with ARDS is a consequence of the failure of normal mechanisms of inflammation resolution and lung tissue repair. This hypothesis is clinically supported by a recent analysis of patients enrolled in the ARDSnet where a ?hyperinflammatory? endotype of ARDS patients was associated with poor clinical outcomes, including death. We propose to investigate the process of recovery from viral pneumonia with a focus on mechanisms that promote resolution of lung inflammation and healthy repair of lung damage. Core A will assist the PPG investigators as they test this central hypothesis of this PPG through a highly integrated and innovative set of experiments by focusing on five Specific Aims: Specific Aim 1. To support communication between the Project Investigators, the Core Leaders, Collaborating investigators, and the Internal and External Advisory Committee members. Specific Aim 2. To provide a structure for the sharing of materials and dissemination of information between the Project Investigators, Core Leaders and their Collaborators. Specific Aim 3. To provide financial and regulatory oversight to the Project and Core Leaders and coordinate their interactions with Institutional Core Services. Specific Aim 4. To disseminate the discoveries made by the program project investigators through publications, presentations and the sharing of resources to other institutions and other investigators. Specific Aim 5. To foster an environment of collaborative interdisciplinary research and mentoring of students, post-doctoral fellows and investigators.
