Inhaled activated protein C: a novel therapy for acute lung injury?

Kathleen D Liu,Mark R Looney,Michael A Matthay

doi:10.1186/cc7869

Abstract

Acute lung injury (ALI) is characterized by the presence of dysregulated coagulation and inflammation. Therefore, Waerhaug and colleagues hypothesized that administration of activated protein C (APC) via the inhaled route would be a novel and effective treatment for ALI. They demonstrated that inhaled APC improved oxygenation and lung aeration in a sheep model of lipopolysaccharide-induced ALI, but did not alter lung water or hemodynamics. Future studies are needed to determine plasma and airspace APC levels when administered by the inhaled route, and to determine if inhaled APC has a similar effect in other models of ALI.

Highlights

Based on human and animal studies demonstrating that pathogenesis of Acute lung injury (ALI) involves exuberant inflammation and coagulation activation [7-9], activated protein C (APC) has been proposed as a treatment for ALI/acute respiratory distress syndrome (ARDS)
In the previous issue of Critical Care, Waerhaug and colleagues [1] test the hypothesis that inhaled activated protein C (APC), a novel therapy approved for the treatment of severe sepsis [2], may be an effective treatment for acute lung injury (ALI)
Based on human and animal studies demonstrating that pathogenesis of ALI involves exuberant inflammation and coagulation activation [7-9], APC has been proposed as a treatment for ALI/ARDS

Summary

Introduction

Based on human and animal studies demonstrating that pathogenesis of ALI involves exuberant inflammation and coagulation activation [7-9], APC has been proposed as a treatment for ALI/ARDS. In the previous issue of Critical Care, Waerhaug and colleagues [1] test the hypothesis that inhaled activated protein C (APC), a novel therapy approved for the treatment of severe sepsis [2], may be an effective treatment for acute lung injury (ALI). Systemic APC administration is associated with a modest increase in the risk of bleeding, which can be life-threatening. Waerhaug and colleagues [1] hypothesized that inhaled aerosolized APC could be effectively delivered to reduce lung injury in a sheep model of lipopolysaccharide (LPS)-induced ALI.

Results

Conclusion