Surfactant inactivation and surfactant therapy in acute respiratory distress syndrome (ARDS)

Abstract

Surfactant dysfunction constitutes an important element in the complex pathophysiology of acute respiratory distress syndrome (ARDS). In this disease, surfactant may become inactivated by plasma proteins leaking into the airspaces as a consequence of increased alveolar permeability. In addition, surfactant proteins may become degraded by proteolytic enzymes or free oxygen radicals released by inflammatory cells recruited to the airspaces. Regardless of the mechanism involved, surfactant inactivation or degradation may be counterbalanced by increasing the pool of surfactant in the airspaces, i.e., by replacement therapy. Surfactant therapy has been tested with promising results in animal models of ARDS triggered by, e.g., lung lavage, hyperoxia or exposure to various toxic agents. In general, the response to surfactant treatment depends on the quality of the surfactant, timing of treatment in relation to the degree of lung injury, dosage and mode of administration. Encouraging results have been obtained with modified natural surfactants in clinical pilot studies on patients with ARDS, justifying further evaluation of this therapeutic approach in randomized controlled trials.