EDITORIAL Revisiting O1-antitrypsin therapy in cystic fibrosis: can it still offer promise?

he contribution of the neutrophil-derived serine pro-tease neutrophil elastase (NE) to lung disease in cystic fibrosis (CF) is unquestioned and yet, despite promising preliminary studies in the last 20 yrs to investigate an effective therapy to negate the damaging effect of NE [1], this treatment has failed to take off for patients with CF. This is largely due to the scarcity of clinical trial data relating to this therapy. However, two recent publications [2, 3] signal a renewed interest in the application of treatment with inhaled O1-antitrypsin (AAT) as a panacea for the proteolytic damage occurring in CF lung disease. NE is released by neutrophils either on the cell membrane during cell migration or into the extracellular space upon stimulation by immune complexes, or by necrotic or apoptotic cells [4]. AAT is one of the most important protease inhibitor