Timing of dornase alpha inhalation does not affect the efficacy of an airway clearance regimen in adults with cystic fibrosis: a randomised crossover trial. Effect of smaller droplet size of dornase alfa on lung function in mild cystic fibrosis. Dornase Alfa Nebulizer Group. A two-year randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities.
Does the timing of inhalation of dornase alpha in relation to physical airway clearance techniques influence the effect of the entire airway clearance regimen?.
                A randomised crossover trial with concealed allocation, intention-to-treat analysis and blinding of patients, therapists, and assessors.
                Twenty adults with cystic fibrosis who were not taking dornase alpha were recruited, of whom 17 were randomised and completed the trial.
                Participants performed an individually tailored session of physical airway clearance techniques for at least 15 minutes per day for 28 days. For 14 days, dornase alpha was inhaled before each session of airway clearance techniques and a placebo was inhaled after. For the other 14 days, placebo was inhaled before and dornase alpha after airway clearance techniques. The order of the two 14-day periods was randomised.
                The primary outcome was the forced expiratory volume in 1 sec (FEV(1)). Secondary outcomes were forced vital capacity, 24-hour sputum production, sputum production during the airway clearance regimen, oxygen saturation, peak oxygen consumption during an incremental exercise test, oxygen desaturation during exercise, and quality of life.
                Inhalation of dornase alpha after airway clearance techniques did not significantly affect the change in FEV(1) compared with inhalation before airway clearance techniques, mean difference 0.04 L, 95% CI -0.14 to 0.23. None of the secondary outcomes differed significantly between the study arms. There was good correlation between the change in FEV(1) and the change in quality of life scores.
                Timing of dornase alpha can be selected according to convenience, patient preference, or to accommodate the timing of other medications in the treatment regimen.
                ACTRN12611001041943.
                Copyright © 2011 Australian Physiotherapy Association. Published by .. All rights reserved. Aerosolized recombinant human DNase (dornase alfa) reduces mucus viscoelasticity in vitro and improves pulmonary function in patients with cystic fibrosis (CF). We postulated that if dornase alfa could be delivered more peripherally to small airways in the lung in the form of smaller aerosol droplets in patients with early airway obstruction, the increase in pulmonary function from baseline might be improved. CF patients (n = 749) with mild lung disease (baseline forced vital capacity > or = 70% predicted) were randomly assigned to receive dornase alfa 2.5 mg daily for 2 weeks by one of two nebulizer systems: 1) the Medic-Aid Durable SideStream nebulizer powered by the MobilAire Compressor (SS/MA) producing a droplet size with a mass median aerodynamic diameter (MMAD) of 2.1 microm; or 2) the Hudson T Up-draft nebulizer with a DeVilbiss Pulmo-Aide compressor (HT/PA) with an MMAD of 4.9 microm. Spirometry was performed at baseline and following 14 days of treatment. Dornase alfa delivered by both nebulizer systems produced small but statistically significant improvements in pulmonary function compared with baseline. There was a trend (P = 0.06) toward greater improvement in forced expiratory flow in 1 s in the SS/MA group (4.3%) compared with the HT/PA group (2.5%). These results indicate that the short-term spirometric response to dornase alfa is influenced in part by the physical characteristics of the aerosol in patients with mild lung disease. We speculate that this may be true for other therapeutic aerosols, and it appears that localization of disease in the lung plays a role in the response to inhaled agents. Our objective was to determine whether long-term treatment of young patients with cystic fibrosis (CF) with dornase alfa maintains lung function and reduces respiratory tract exacerbations.
                This was a 96-week, randomized, double-blind, placebo-controlled trial involving 49 CF centers. Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85% predicted. Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months. Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor.
                Patients were randomized, 239 to dornase alfa and 235 to placebo. At baseline the mean age was 8.4 years, the mean forced expiratory volume in 1 second 95% predicted, the mean forced expiratory flow, midexpiratory phase 85% predicted, and the mean forced vital capacity 102% predicted. At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted (mean +/- SE) was 3.2 +/- 1.2 for forced expiratory volume in 1 second (P =.006), 7.9 +/- 2.3 for forced expiratory flow between 25% and 75% of vital capacity (P =.0008), and 0.7 +/- 1.0 for forced vital capacity (P =.51). The risk of respiratory tract exacerbation was reduced by 34% in patients who received dornase alfa (relative risk 0.66, P =.048). There was no statistically significant difference between the groups in changes in weight-for-age percentile. Adverse event profiles for the treatment groups were similar.
                Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period.
The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.