Is a longer time interval between recombinant human deoxyribonuclease (dornase alfa) and chest physiotherapy better?: A multi-center, randomized crossover trial

Background Although the benefits of recombinant human deoxyribonuclease (dornase alfa) in patients with cystic fibrosis (CF) are established, its optimal timing in relation to physiotherapy is unknown. As its enzymatic effect lasts for 6–11 hr, dornase alfa may be more efficacious if the time interval between inhalation and chest physiotherapy is increased. The aim of this study was to investigate if a longer time interval between dornase alfa nebulization and chest physiotherapy improves clinical outcomes of subjects with CF. Methods A single‐blind randomized cross‐over trial was conducted on subjects with CF from outpatients of four hospitals. Subjects were in stable health and studied over 6 weeks (utilizing 14‐day blocks of morning or evening dornase alfa administration with 14 days washout). Usual regimens for physiotherapy and exercise were unaltered. Thus changing the times altered the dwell time of dornase alfa prior to physiotherapy. Long interval was defined as dwell time of >6 hr and short as ≤6 hr. Outcomes were measured at pre and post each regimen. Results Twenty subjects aged 7–40 years completed the study. At end of long interval regimen, (median interval = 11.1 hr), FEF25–75% and CF‐specific quality of life significantly improved compared to baseline values and to short interval regimen (median interval = 0.25 hr) outcomes. FVC, FEV1, sputum weights, and adherence were similar in both regimens. Conclusions A longer time interval between dornase alfa and physiotherapy is more efficacious than short interval. Administration timing of dornase alfa based on patient choice to incorporate longer interval time is likely to be the best regimen for patients previously established on dornase alfa nebulization. Pediatr Pulmonol. 2007; 42:1110–1116. © 2007 Wiley‐Liss, Inc.