Inhalation of alpha(1)-protease inhibitor in cystic fibrosis does not affect surfactant convertase and surface...

The inhalation of alpha(1)-protease inhibitor (alpha(1)-PI) was assessed in a pilot study to restore the protease-antiprotease balance in the lungs of cystic fibrosis (CF) patients. In addition, the effect of this treatment on the surface active properties of lung surfactant and the metabolic conversion of aggregate forms was studied. Eight young adults with CF inhaled 100 mg of alpha(1)-PI twice daily over 8 weeks and bronchoalveolar lavages (BAL) were obtained before and 12 h after the last inhalation. Large aggregate (LA) forms of surfactant were isolated from the in vivo material by ultracentrifugation and their conversion into small aggregates (SA) was assessed by an in vitro surface area cycling assay. Although alpha(1)-PI partially restored the protease-anti-protease imbalance and reduced BAL protein content, no effects were noted on the impaired minimal surface tension and on the in vivo and in vitro conversion of LA to SA. Antiserum against the specific carboxyl esterase ES-2, previously identified in mice and rats as the putative surfactant convertase, did not detect a protein of the appropriate size in CF BAL. Whereas short-term inhalation of alpha(1)-PI was beneficial for the proteolytic aspects of CF lung injury, this appeared not to be the case for surfactant conversion and surface activity.