Editorial Views  |   March 2019
Acute Respiratory Distress Syndrome: Biomarkers, Mechanisms, and Water Channels
Author Notes
  • From the Institute of Physiology, Charité-Universitätsmedizin Berlin, Germany; Keenan Research Centre for Biomedical Science, St. Michael’s Hospital, Toronto, Ontario, Canada; and Departments of Physiology and Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Accepted for publication December 7, 2018.
    Accepted for publication December 7, 2018.×
  • Corresponding article on page 404.
    Corresponding article on page 404.×
  • Address correspondence to Dr. Kuebler: wolfgang.kuebler@charite.de
Article Information
Editorial Views / Critical Care / Respiratory System
Editorial Views   |   March 2019
Acute Respiratory Distress Syndrome: Biomarkers, Mechanisms, and Water Channels
Anesthesiology 3 2019, Vol.130, 364-366. doi:10.1097/ALN.0000000000002607
Anesthesiology 3 2019, Vol.130, 364-366. doi:10.1097/ALN.0000000000002607
Despite five decades of research since its description in 1967, the acute respiratory distress syndrome (ARDS) remains a frequent killer among critically ill patients. Insight into the detrimental effects of mechanical ventilation has improved supportive therapy (e.g., low tidal volume ventilation and prone positioning), yet all pharmacologic or cell therapy–based interventions have so far failed, and mortality remains unabatedly high at up to 40%. One important confounder that may have precluded the development of effective pharmacotherapies so far is the fact that ARDS is a syndrome rather than a disease. In other words, ARDS reflects the result of a diverse range of direct pulmonary or indirect extrapulmonary triggers or diseases. These include bacterial and viral pneumonia, aspiration of gastric contents, lung contusion, or inhalation injury—all causes of “direct” lung injury, as well as multiple causes of “indirect” lung injury such as sepsis, severe trauma, transfusions, pancreatitis, or drug reactions. Although these different etiologies share common pathologic features in terms of an excessive inflammatory response, alveolo–capillary barrier failure, and formation of a proteinaceous lung edema, and they are identified by a few generalized clinical features (bilateral opacities on chest imaging, respiratory failure not fully explained by cardiac failure, and impaired oxygenation: the 2012 Berlin definition of ARDS), this does not mean that they share similar disease pathways. Patient factors—both genetic and acquired—will likely impact not only on individual susceptibility, but also on the course of the disease and the effectiveness of specific treatments. Although a single therapeutic “magic bullet” may work in a highly standardized preclinical model with syngenic, same-sex animals without comorbidities, it will fail in a real-world scenario of ARDS. This is not a shortcoming of the animal model—the same limitations apply for cell or organoid systems, isolated human lungs, or even healthy volunteers—but it is inevitable if we insist on a simplistic “one size fits all” solution that may not be achievable.