Aerosolized Dornase alpha (rhDNase) in cystic fibrosis

Abstract

Advances in the treatment and management of respiratory and pancreatic disorders has increased the life expectancy of patients with cystic fibrosis to 28 years (1). Despite the use of potent antibiotics and chest physiotherapy, persistent bacterial infection of the lung is the major cause of morbidity and mortality in these patients (2). This occurs, in part, because of the production of copious amounts of pulmonary secretions. It has been found that these secretions contain high amounts of human DNA (3-8). This high DNA concentration causes two problems. First, it increases the viscosity of sputum. This, in conjunction with reduced mucociliary clearance, decreases the removal of sputum. Second, the DNA binds to aminoglycosides, which decreases their antimicrobial efficacy (9, 10). Until recently there was no effective drug to decrease the viscosity of sputum in patients with cystic fibrosis. Dornase alpha (Pulmozyme) is the first drug to offer a safe and effective method to treat excessive DNA in sputum. In vitro studies demonstrated that rhDNase greatly decreased the viscosity of sputum by decreasing the concentration of DNA in a concentration-dependent manner (11).

Going the Extra Mile: Why Clinical Research in Cystic Fibrosis Must Include Children

“…Using CF as an example, dornase alfa acts by breaking down extracellular DNA in the airway lumen, reducing the viscosity and aiding clearance of mucus. The substrate for clinical efficacy, airway inflammation, will likely mean efficacy differences between adults (more established disease) and children/infants (earlier disease and healthier airways) [ 43 ]. In contrast, novel small molecule CFTR modulators improve the function of CFTR in all body systems affected in CF [ 44 ].…”