RhDNase before airway clearance therapy improves airway patency in children with CF. Timing of dornase alpha inhalation does not affect the efficacy of an airway clearance regimen in adults with cystic fibrosis: a randomised crossover trial. Recombinant human DNase nebulisation in children with cystic fibrosis: before bedtime or after waking up?
Little is known about the optimal timing of rhDNase nebulization in relation to airway clearance therapy (ACT).
                To compare the effects of rhDNase before ACT versus rhDNase after ACT in children with CF.
                Design: randomized, double blind, double dummy, cross over study. Inclusion criteria: CF, stable clinical condition, rhDNase maintenance therapy. Children in Group I inhaled rhDNase 30 minutes before ACT, and placebo directly after ACT in week 1-3. The protocol was reversed during week 4-6. Group II performed the reversed sequence. Patients continued their daily routine ACT. Primary endpoint: MEF(25) %pred. Pulmonary functions tests were performed on days 0, 14, 21, 35 and 42. In weeks 3 and 6 children scored cough and sputum production on daily diary cards.
                24 patients completed the study. Mean age = 12 years (range 7-19). Mean MEF(25) %pred was 5.8% higher after 3 weeks of rhDNase before ACT, compared to rhDNase after ACT (58.3% vs 52.5%, p=0.01). There were no significant differences for any of the other variables.
                Inhalation of rhDNase before ACT improves peripheral airway patency in children with cystic fibrosis. Since all children were already on maintenance rhDNase therapy before the study, this effect is additional to any existing effect of regular rhDNase. 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. The present study focused on patients with cystic fibrosis (CF), who were on maintenance therapy with recombinant human deoxyribonuclease (rhDNase), with the aim of comparing efficacy and possible side effects of nebulisation of rhDNase when taken before bedtime with efficacy and side effects when taken after waking up. A randomised, double-blind, double-dummy, crossover study group was used. The inclusion criteria were as follows: 1) CF, 2) stable clinical condition and 3) rhDNase maintenance therapy. Patients in group I inhaled rhDNase before bedtime and a placebo after waking up in weeks 1-2. The protocol was reversed during weeks 3-4. Group II patients performed the reverse of this sequence. Patients continued with their daily routine sputum expectoration. The primary end-point was classified as the maximal instantaneous forced flow when 25% of the forced vital capacity remained to be exhaled (MEF(25%)). Pulmonary functions tests were performed on days 0, 7, 14, 21 and 28. At 1, 2, 3 and 4 weeks arterial oxygen saturation and cough frequency were measured during the night. A total of 24 patients completed the study. The mean (range) age of the patients was 13 (6-19) yrs. MEF(25%), taken to be the primary end-point, did not show a significant difference between nebulisation of rhDNase before bedtime compared with when taken after waking up. Nocturnal cough, oxygen saturation, and other secondary end-points were not significantly different between the two study periods. In conclusion, the present study found that it is equally effective and safe to nebulise recombinant human deoxyribonuclease before bedtime compared with when performed after waking up in children with cystic fibrosis, who are on maintenance treatment with recombinant human deoxyribonuclease.
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.