Lessons learned in acute respiratory distress syndrome from the animal laboratory

Since the description of the acute respiratory distress syndrome (ARDS) in 1967, investigators have struggled to reproduce the syndrome in the animal laboratory. While several different models of experimental acute lung injury (ALI) have been developed, none completely capture the inciting etiologies, initial inflammation, heterogeneity, and resolution of human ARDS. This potentially has contributed to the poor translation of potential therapeutics between animal ALI models and human ARDS. It was only recently that standardized criteria were suggested for what makes an ALI model comparable to human ARDS. Nevertheless, despite model heterogeneity, these models have contributed substantially to our understanding of the syndrome. From the initial studies identifying the risks of mechanical ventilation to the identification of potentially targetable inflammatory mediators, to modern studies focusing on regional heterogeneity and novel molecular pathways, animal models continue to inform our understanding of ARDS. This review will cover several major lessons learned from animal models of ALI, and provide some direction for future studies in this field.