Human neutrophil elastase and lung surfactant in acute respiratory distress syndrome

Human Neutrophil Elastase (HNE) is one of the main proteases secreted into the alveolar space by infiltrated neutro- phils during several inflammatory lung diseases such as cystic fibrosis, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Consequently, a number of therapeutic approaches based on the specific inhibition of HNE are currently under investigation. The present work reviews the physiopathological role of HNE in ALI/ARDS and its relationship to the pulmonary surfactant system, as well as the clinical potential of protease inhibitors in this setting. In spite of the complex physiopathology of these diseases, the available evidence points to a direct link bet- ween HNE and ALI/ARDS, with increased local concentrations of this protease in animal models of ALI as well as in patients. Furthermore, the unbalanced ratio of protease/endogenous inhibitors characteristic of these disorders has led to the pharmacological and clinical evaluation of HNE inhibitors, examining their addition to currently available exogenous surfactant with promising results.