What is ARDS?

Acute respiratory distress syndrome (ARDS) is a severe form of acute respiratory failure characterized clinically by acute onset of shortness of breath, hypoxemia and bilateral infiltrates on chest imaging. ARDS is a syndrome occurring most commonly in response to pneumonia, sepsis, trauma, blood transfusion and, in the last year, COVID-19.

ARDS continues to be a major challenge in critical care medicine with high short- and long-term mortality rates. There are currently no targeted pharmacologic therapies to treat this syndrome, and treatment is focused on supportive care, protective mechanical ventilation, and conservative fluid management.

The biology of lung injury in ARDS:

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ARDS is characterized by:

  • Loss of alveolar capillary barrier integrity

  • Accumulation of protein rich edema fluid in the airspace

  • Influx of inflammatory cells

  • Activation of intra-alveolar coagulation

  • Formation of fibrin-rich hyaline membranse

From Ware, Matthay

The Acute Respiratory Distress Syndrome NEJM 2000

CELL-FREE HEMOGLOBIN IN THE AIRSPACE

Our group discovered that Cell-free hemoglobin (CFH) causes increased inflammation and permeability in the absence of any other stimulus. Thus, CFH is a novel endogenous mediator of ARDS.

ONGOING PROJECTS

  • Understanding the cellular and molecular mechanisms underlying CFH mediated increased alveolar capillary barrier permeability

  • Defining the effects of CFH on regulating alveolar macrophage function

  • Identifying the mechanisms of CFH uptake and processing in the alveolar epithelium

MAPPING THE INJURED LUNG

In recent years, it has become clear that ARDS is a biologically heterogenous syndrome. Our group is using state-of-the-art single cell and imaging techniques to define the cellular and molecular heterogeneity in the injured human lung

ONGOING PROJECTS

  • Study the cellular landscape using single nuclear RNASeq of injured and uninjured human lungs

  • Spatially define the whole lung proteome in the injured and uninjured lung

  • Measure the spatial distribution of the lung transcriptome using RNA Scope on live lung slices

  • Define the radiographic heterogeneity of experimental lung injury using micro-CT

ANALYSIS OF BIOMARKERS IN EXHALED BREATH

Our group recently published a novel method of sampling the distal airspace in ARDS by extracting fluid accumulated in Heat Moisture Exchange Filters collected from intubated patients with ARDS and critically ill control subjects. This fluid is highly reflective of the biologic changes in the distal airspace. 

ONGOING PROJECTS

  • Define the proteomic signature of HME fluid throughout the course of ARDS

  • Use biomarkers measured in HME fluid to understand ARDS heterogenity

  • In collaboration with Dr. Angela Rogers, Assistant Professor of Medicine, Stanford, study the metabolomic profile of ARDS using HME fluid

UNDERSTANDING THE LUNG EPITHELIAL GLYCOCALYX

In collaboration with Dr. Eric Schmidt, Professor of Medicine, University of Colorado, we are working to understand the biologic consequences of shedding of the alveolar epithelial glycocalyx in lung injury.

ONGOING PROJECTS

  • Studying the cellular consequences of alveolar epithelial glycocalyx shedding in the lung epithelium