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Should we shift the paradigm of preclinical models for ARDS therapies?
  1. William Bain1,
  2. Gustavo Matute-Bello2,3
  1. 1 Department of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  2. 2 Center for Lung Biology, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA
  3. 3 Veterans Administration Puget Sound Healthcare System, Seattle, WA, United States
  1. Correspondence to Dr Gustavo Matute-Bello, Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA 98109, USA; matuteb{at}uw.edu

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The acute respiratory distress syndrome (ARDS) is characterised by diffuse impairment in gas exchange that can result from heterogenous aetiologies. ARDS causes 10% of intensive care unit admissions worldwide with inpatient mortality rates ranging from 35% for mild cases to 46% for severe cases.1 Despite being a common and frequently fatal process, there are no widely accepted pharmacological therapies available to treat ARDS, the management of which primarily rests on appropriate mechanical ventilation and supportive care.2 Unfortunately, numerous promising pharmacological therapies that demonstrated benefit in preclinical models or early clinical investigation have failed to demonstrate reliable improvement in clinical outcomes.3–7 In the context of a persistent clinical problem that has vexed state-of-the art investigative therapies, there have been thoughtful proposals on how to improve the investigation of potential ARDS therapies in experimental animal models of acute lung injury (ALI).8–10 A 2011 American Thoracic Society (ATS) statement defined experimental ALI as an acute process (ie, sequelae develop within 24 hours of exposure) with increased permeability of the alveolar-capillary membrane, frequently with histopathological correlation, leading to impairments in lung physiology.8 Building on these earlier proposals, Oakley and colleagues11 propose in this issue of Thorax two broad, fundamental changes in the philosophical framework for the investigation of novel therapeutics in preclinical ARDS models.

The first fundamental change to the 2011 ATS definition proposed by Oakley et al 11 is that experimental animal models used to assess the clinical efficacy of proposed ARDS therapeutics should be clinically relevant. Specifically, the authors highlight three criteria to define an effective model based on the notion that the clinical conditions of animal models should reflect as best as possible the clinical conditions of human patients that would receive the experimental therapy. First, ARDS therapies should be tested in lungs with pre-existing injury …

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