Embracing the heterogeneity of lung injury: a bedside to bench to bedside perspective

Symposium — Tuesday, April 25, 2024 — 8:00 AM - 10:00 AM — , Room W196B
Respiration Section — Chair: Steven Dudek — Co-Chair: Ciara Shaver

Acute Respiratory Distress Syndrome (ARDS) is a devastating illness with an annual incidence of 200,000 and a mortality of 40%. Clinical trials in ARDS have been uniformly disappointing, perhaps reflecting an inappropriate homogenization of ARDS as a single disease state.  Indeed, ARDS pathophysiology varies greatly based upon triggering insult (e.g. direct injury to the lung versus indirect, systemic injury).  This session will translate phenotypic differences observed in ARDS trials to mechanistic differences identified in animal models of ARDS pathobiology.  In doing so, we intend to highlight opportunities for individualized management of this highly morbid disease.    Dr Calfees data suggest that there are sub-phenotypes within ARDS patients that clearly connote diverging outcomes. Furthermore her data show that the etiology of ARDS (direct versus indirect insults) is associated with unique molecular phenotypes. Dr. Damarlas laboratory is focused on the mechanistic impact of endothelial cell apoptosis on vascular permeability using animal models. His data show that indirect models of lung injury lead to a disruption of the endothelial barrier but not the epithelial barrier.  Dr. Schmidts laboratory investigates the role of matrix glycoproteins and proteoglycans in the development of lung injury, and how the glycobiology of lung injury varies greatly according to triggering insult. Dr. Bastaraches laboratory is focused on alveolar epithelial cell biology and its role in lung injury, with attention to mechanistic differences between direct and indirect lung injury. Dr. Dudek has national expertise in the pathobiology of ARDS and, as such, can identify future challenges and opportunities in personalizing ARDS care.   We believe that this session will help define the role of several key cellular compartments involved in lung injury and highlight that varying causes of lung injury may affect various cell types differently, thereby necessitating individualized therapies.

Speakers

• Not a single disease state:  molecular subphenotypes of lung injury in human trials
  Carolyn Calfee — Department of Medicine, University of California San Francisco


• Insult-specific glycobiology signatures of critical illness: impact on lung injury
  Eric Schmidt — Department of Medicine, University of Colorado


• Distinct endothelial responses to lung injury insults:  a role for apoptosis
  Mahendra Damarla — Department of Medicine, Johns Hopkins University


• Distinct roles of Tissue Factor in direct and indirect acute lung injury
  Julie Bastarache — Department of Medicine, Vanderbilt University


• An individualized approach to ARDS:  where do we go from here?
  Steven Dudek — Department of Medicine, University of Illinois Chicago