Inhaled steroids for the treatment of acute respiratory distress syndrome in animal studies

Learning Objectives: Acute Respiratory Distress Syndrome (ARDS) is defined as non-cardiogenic pulmonary edema caused by damage to the alveolar epithelial-endothelial barrier. This disruption results in the accumulation of inflammatory fluid in the alveolar space, leading to worsening oxygenation. Currently there is no definitive therapy to change the outcome in ARDS. Inhaled steroids have been studied in animal models of ARDS for the past 30 years. These studies have not yet been translated into human studies. We present a systematic review of those animal studies. Methods: Systematic review of animal studies based on an extensive literature search in PUBMED, Embase, SCOPUS and Web of science, non-limited to English language. Search terms, including MESH terms: Animals (as key word and on limitations), ARDS, ALI, Corticosteroids, steroids, Inhaled, Budesonide, Beclomethasone. We included studies from 1990 to 2016. We included studies using mammalian species. We included studies with induced ALI or ARDS via biological or mechanical injury, but excluded chemical injury by chlorine or phosgene gas. The intervention arm in these studies was the use of inhaled steroids, we excluded studies with multiple intervention drugs. We only included studies with control or placebo groups. Results: We identified 36 studies, 7 met our criteria. All of the injuries were generated by intravenous infusions of bacteria or bacterial components, except one study that used high tidal-volume induced lung injury. All studies showed an improvement of inflammatory markers in the inhaled steroids groups (bronchoalveolar lavage, serum or histopathology). All studies showed an improvement in oxygenation parameters in the steroid groups. Four studies measured mortality with improved outcomes in the steroid group in three studies while one found no difference. Conclusions: The use of inhaled steroids in animal models of induced ARDS, show improvement of oxygenation, decreased lung permeability and decreased inflammation. The hemodynamic measurements showed that patients that received steroids had lower PVR. Treatment with inhaled steroids was associated with lower mortality in three studies. We believe there is sufficient animal data to warrant the investigation of this therapeutic modality in humans with ARDS.