The flow of participants through the trial is illustrated in Figure 1. The characteristics of the participants were similar at the start of each arm of the study (Table 1 and the first two columns of Table 2). Twelve

participants were using positive expiratory pressure as their physical airway clearance technique. Seven participants were using active cycle of breathing techniques, of whom 4 were using percussion as well. One participant used positive expiratory pressure once daily and percussion once daily. The airway clearance regimen, including tailoring of the physical techniques and confirming the appropriate nebulisation procedures, was determined by the Cystic Fibrosis Unit physiotherapist, who had 6 years of clinical experience, AP24534 mw including 4 years in the cystic fibrosis area. The Cystic Fibrosis Unit of Westmead Gemcitabine molecular weight Hospital in Sydney was the only centre to recruit and test patients in the trial. The Cystic Fibrosis Unit managed approximately 60 adult patients during the time of the study. All randomised participants completed both arms of the trial. According to diary card entries and vial counts, compliance with the allocated therapies was > 85%. No participants in either arm had adverse clinical changes during the

intervention that required cessation of the intervention. One participant with a history of recurrent haemoptysis had a single episode after the first 14-day intervention period (during which he was taking dornase alpha before airway clearance techniques). This was considered unlikely to be related to treatment and resolved spontaneously despite

continuation of the allocated treatment regimen. Group data for all outcomes for the experimental and control interventions are presented in Tables 2 and 3, while individual data are presented in Table 4 (see eAddenda for Table 4). The timing of the inhalation of dornase alpha did not have statistically significant others effects on lung function. The best estimate of the average effect of changing from inhaling dornase alpha before to after the physical techniques was to increase FEV1 by only 40 mL (95% CI –140 to 230 mL). When the FEV1 data were considered in terms of a percentage of the predicted value, the best estimate of the effect and the limits of the confidence interval all indicated that any effect was too small to be clinically worthwhile. FVC tended to favour the inhalation of dornase alpha before airway clearance techniques, but the result was only of borderline statistical significance. Daily sputum production did not appear to be influenced by the timing regimen, and nor did the amount of sputum obtained during the airway clearance regimen as a proportion of the daily amount. There was little change in resting oxygen saturation levels in all participants throughout both arms of the study. The timing of inhalation of dornase alpha did not have a significant effect on this outcome.