Small airway deposition of dornase alfa during exacerbations in cystic fibrosis; a randomized controlled clinical trial

Small airway obstruction is important in the pathophysiology of cystic fibrosis (CF) lung disease. Additionally, many CF patients lose lung function in the long term as a result of respiratory tract exacerbations (RTEs). No trials have been performed to optimize mucolytic therapy during a RTE. We investigated whether specifically targeting dornase alfa to the small airways improves small airway obstruction during RTEs. Methods In a multi‐center, double‐blind, randomized controlled trial CF patients hospitalized for a RTE and on maintenance treatment with dornase alfa were switched to a smart nebulizer. Patients were randomized to small airway deposition (n = 19) or large airway deposition (n = 19) of dornase alfa for at least 7 days. Primary endpoint was forced expiratory flow at 75% of forced vital capacity (FEF 75 ). Main Results Spirometry parameters improved significantly during admission, but the difference in mean change in FEF 75 between treatment groups was not significant: 0.7 SD, P  = 0.30. FEF 25–75 , FEV 1 , nocturnal oxygen saturation and diary symptom scores also did not differ between groups. Conclusions This study did not detect a difference if inhaled dornase alfa was targeted to small versus large airways during a RTE. However, the 95% confidence interval for the change in FEF 75 was wide. Further studies are needed to improve the effectiveness of RTE treatment in CF. Pediatr Pulmonol. 2014; 49:154–161. © 2013 Wiley Periodicals, Inc.