AEROSOLIZED DORNASE-ALPHA (RHDNASE) IN CYSTIC-FIBROSIS

Advances in the treatment and management of respiratory and pancreatic disorders has increased the life expectancy of patients with cystic f ibrosis to 28 years (1). Despite the use of potent antibiotics and che st physiotherapy, persistent bacterial infection of the lung is the ma jor cause of morbidity and mortality in these patients (2). This occur s, in part, because of the production of copious amounts of pulmonary secretions. It has been found that these secretions contain high amoun ts of human DNA (3-8). This high DNA concentration causes two problems . First, it increases the viscosity of sputum. This, in conjunction wi th reduced mucociliary clearance, decreases the removal of sputum. Sec ond, the DNA binds to aminoglycosides, which decreases their antimicro bial efficacy (9, 10). Until recently there was no effective drug to d ecrease the viscosity of sputum in patients with cystic fibrosis. Dorn ase alpha (Pulmozyme (R)) is the first drug to offer a safe and effect ive method to treat excessive DNA in sputum. In vitro studies demonstr ated that rhDNase greatly decreased the viscosity of sputum by decreas ing the concentration of DNA in a concentration-dependent manner (11).