Α1-Antitrypsin: Key Player or Bystander in Acute Respiratory Distress Syndrome?. (15th March 2021)

• Record Type: Journal Article
• Authors: Hogan, Grace; Geoghegan, Pierce; Carroll, Tomás P.; Clarke, Jennifer; McElvaney, Oisín F.; McElvaney, Oliver J.; McElvaney, Noel G.; Curley, Gerard F.
• Is Part Of: Anesthesiology. Volume 134:Number 5(2021)
• Page Start: 792
• Page End: 808
• Publication Date: 2021-03-15
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000003727
• Languages: English
• ISSNs: 0003-3022

Abstract

Abstract : Acute respiratory distress syndrome is characterized by hypoxemia, altered alveolar–capillary permeability, and neutrophil-dominated inflammatory pulmonary edema. Despite decades of research, an effective drug therapy for acute respiratory distress syndrome remains elusive. The ideal pharmacotherapy for acute respiratory distress syndrome should demonstrate antiprotease activity and target injurious inflammatory pathways while maintaining host defense against infection. Furthermore, a drug with a reputable safety profile, low possibility of off-target effects, and well-known pharmacokinetics would be desirable. The endogenous 52-kd serine protease α1-antitrypsin has the potential to be a novel treatment option for acute respiratory distress syndrome. The main function of α1-antitrypsin is as an antiprotease, targeting neutrophil elastase in particular. However, studies have also highlighted the role of α1-antitrypsin in the modulation of inflammation and bacterial clearance. In light of the current SARS-CoV-2 pandemic, the identification of a treatment for acute respiratory distress syndrome is even more pertinent, and α1-antitrypsin has been implicated in the inflammatory response to SARS-CoV-2 infection. Abstract : New therapies are urgently required for acute respiratory distress syndrome, particularly in the context of the current SARS-CoV-2 pandemic. The endogenously produced protein α1-antitrypsin is a potential treatment option because of its potent antielastase, immunomodulatory, and bactericidal effects.