AEROSOLIZED RHDNASE IN CYSTIC-FIBROSIS - EFFECT ON LEUKOCYTE PROTEASES IN SPUTUM

In cystic fibrosis (CF), large amounts of free leucocyte proteases are present in bronchial secretions, contributing to progressive lung dam age, Recombinant, human deoxyribonuclease (rhDNase) is a new therapeut ic agent that decreases sputum viscosity, However, deoxyribonuclease h as been shown, in vitro, to release cationic enzymes from complexes wi th deoxyribonucleic acid (DNA), The present study was conducted to ass ess this effect in vivo. Free human leucocyte elastase (HLE), human le ucocyte cathepsin G (HCG), total chemotactic activity, and interleukin -8 (IL-8) were determined in sputum from eight patients before, during and after rhDNase treatment. After 15 days of treatment, HLE activity increased by 81+/-44% (NS), and HCG by 189+/-70% (p<0.05). One week a fter stopping a 4-6 months treatment, HLE activity decreased by 35+/-1 8% (p<0.05), and HCG by 43+/-11% (p<0.05). Sputum bacterial density, c hemotactic activity, and IL-8 concentration did not change. Thus, trea tment with rhDNase can indeed increase the activity of HLE and HCG in the bronchial secretions of CF patients, and this effect is still dete ctable after several months of treatment, If this can be shown to be c linically relevant, combination therapy of recombinant human deoxyribo nuclease with protease inhibitors should be considered as an approach to the problem.