The Use of Human Deoxyribonuclease (rhDNase) in the Management of Cystic Fibrosis

Abstract

In patients with cystic fibrosis (CF), the poor clearance of airway secretions promotes recurrent cycles of pulmonary infection and inflammation. In recent years, novel drugs have been developed to alter the properties of the secretions in an attempt to aid chest physiotherapy in improving airway clearance. Once-daily nebulised recombinant human deoxyribonuclease (rhDNase; dornase alfa; Pulmozyme) is the most widely used mucoactive therapy in patients with CF. It has been shown to reduce the viscoelasticity of sputum from patients with CF and enhance the clearance of secretions. Clinical trials have shown rhDNase to be a well tolerated treatment that improves pulmonary function and reduces respiratory exacerbations. However, the response to treatment is heterogeneous and only a proportion of patients with CF actually benefit from the treatment. At present, we are unable to predict which patients will benefit from rhDNase. Many CF centers have developed formal n-of-1 trials of treatment to find out who benefits and to justify prescribing the agent. rhDNase is an expensive therapy and is mainly used in patients over the age of 5 years with moderate to severe lung disease. However, studies have shown that rhDNase may be useful in patients with milder lung disease. Comparisons with another mucoactive drug, hypertonic saline, have shown rhDNase to be more effective. Recently, it has been shown that giving rhDNase on an alternate-day basis, rather than daily, is equally effective, potentially reducing costs and treatment time.

Using N-of-1 Trials to Improve Patient Management and Save Costs

“…Some centers routinely use N-of-1 trials in clinical practice, for example some cystic fibrosis centers have developed N-of-1 trials of rhDNase. 21 There are several limitations of these three studies. In this analysis, outcomes were dichotomized as responder or nonresponder.…”

Chelated iron sources are inhibitors ofPseudomonas aeruginosabiofilms and distribute efficiently in anin vitromodel of drug delivery to the human lung

“…Indeed, nebulized pharmaceuticals are used by virtually all CF patients who undergo medical treatments. These include PulmozymeÔ, a recombinant form of DNAse I that thins mucosal secretions (Shak 1995;Suri 2005), and TOBIÔ, an inhaled form of the antibiotic tobramycin to treat P. aeruginosa infections (Geller et al 2002;Cheer et al 2003;Murphy et al 2004). These treatments allow for comparatively massive concentrations of antibiotic or other pharmacological agent to be administered to the lungs, concentrations that would be impractical or even deleterious if given systemically.…”

Applications of the Atomic Force Microscope in the Development of Propellant-based Inhalation Formulations

“…Perhaps one of the most notable challenges has been with respect to formulation of product development. For example, protein and gene delivery to the lungs hold great promise in the treatment of clinically important diseases such as cystic fibrosis 11) and lung cancer 12) .…”