Sinonasal inhalation of dornase alfa in CF: A double-blind placebo-controlled cross-over pilot trial

Abstract

Objective: The paranasal sinuses are almost always involved in cystic fibrosis, and chronic rhinosinusitis and nasal polyps are very frequent in the disease. Hereby, the patients' quality of life and their overall health are relevantly impaired. Although dornase alfa, a mucolytic agent, may also be effective in the upper airways, deposition of inhaled drugs into paranasal sinuses is substantially limited. The novel PARI SINUS™ nebuliser has been shown in deposition studies to deliver aerosol into paranasal sinuses but has not yet been clinically tested. This DBPC pilot-trial applying dornase alfa aims to evaluate outcome parameters and sample sizes for a subsequent efficacy trial.

Methods: Primary outcome parameters assessed were the Sino-Nasal Outcome Test (SNOT-20, a disease-specific quality of life assessment tool) and ventilated volume as measured by magnetic resonance imaging. Five CF patients were randomised to inhale either dornase alfa or 0.9% NaCl for 28 days and, after a wash-out period of 28 days, crossed over to the alternative treatment.

Results: Whereas normal saline was not associated with relevant changes in SNOT-20 scores, dornase alfa improved quality of life (p=0.043). MRI results showed no definite trend.

Conclusion: This first clinical study with the novel device gives promising results for the new therapeutic concept of sinonasal inhalation with vibrating aerosols in regard to further analysis involving larger collectives.