DOSE-DEPENDENT IN-VITRO EFFECT OF RECOMBINANT HUMAN DNASE ON RHEOLOGICAL AND TRANSPORT-PROPERTIES OF CYSTIC-FIBROSIS RESPIRATORY MUCUS

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis (CF) respiratory muc us, to improve pulmonary function and to reduce the risk of respirator y tract infectious exacerbations, but its effect on mucus transportabi lity has not so far been investigated. The dose-dependent effect of rh DNase was analysed in vitro on mucus transport rate (tr) by ciliary ac tivity and by simulated cough (cough transport (ct)), as well as on mu cus viscosity and surface properties, Purulent CF sputa (n=15) were in cubated for 30 min at 37 degrees C with either rhDNase at three differ ent concentrations (final concentrations 0.2, 2 or 20 mu g ml(-1) of m ucus) or placebo. No significant dose-dependent effect of rhDNase on t he mucociliary transport rate was observed when the samples were stati stically analysed together, However, in the larger group of mucus samp les (n-11) with a low initial mucociliary transport rate, the latter w as improved at each rhDNase concentration (tr(0.2)=0.69, tr(2)=0.88 an d tr(20)=0.87) as compared to placebo (tr(p)=0.58), In the smaller gro up of mucus samples (n=4) with high initial transport rate, a decrease in mucociliary transport rate was observed, particularly at the highe st concentration rhDNase assayed, ie. 20 mu g ml(-1) of mucus (tr(20)= 0.58) as compared to placebo (tr(p)=0.86), The mucus cough transport w as increased by rhDNase (ct(0.2)=25 mm, ct(2)=27.5 mm and ct(20)=31 mm ) as compared to placebo (ct(p)=23.5 mm), The alterations in the mucus transport capacity were associated with a decrease in mucus viscosity and an improvement in mucus surface properties. These results suggest that rhDNase, at concentrations found in respiratory mucus after inha lation of the recommended therapeutic dose, improves both the cough an d mucociliary transport of CF mucus samples characterized by a low muc ociliary transport rate.