We wish to thank Dr Kathy Stiller and Dr Kylie Hill for their insightful comments on the protocol for this

systematic review. “
“Treatment of sputum retention and the associated chronic infection in the airways of people with cystic fibrosis involves several therapeutic approaches. Antibiotics are administered to suppress infection (Southern et al 2004, Ryan et al 2003, Smyth and Walters 2003), manual physiotherapy techniques and other physical interventions are used to clear infected mucus from the airways (van der Schans et al 2000), and various mucoactive medications are used to see more improve the properties of the mucus to facilitate its clearance (Jones and Wallis 2010, Wark and McDonald 2009). One of these mucoactive medications is recombinant human deoxyribonuclease, or dornase alpha (Pulmozyme®). It reduces the viscosity of sputum in people with cystic fibrosis by cleaving strands of the deoxyribonucleic acid (DNA) released by neutrophils (Lieberman 1968). This makes the sputum flow more easily (Shak et al 1990). Regular use of dornase alpha improves lung function and quality of life, and reduces the number and severity of respiratory exacerbations (Hubbard et al 1992, Ramsey et al 1993, Fuchs et al 1994). Although dornase alpha has been used widely in the management of cystic fibrosis for more than 15 years, the optimal timing of administration with respect to physical airway

clearance techniques is still unclear. During its clinical development, trials Cediranib (AZD2171) allowed dornase alpha to be administered either before or after RAD001 order physical airway clearance techniques. Only recently have trials started to address this potentially important aspect of its administration. Fitzgerald and colleagues (2005) compared administration of dornase alpha 30 min before and 30 min after physical airway clearance techniques in children and adolescents with cystic fibrosis. They found that the two timing regimens had similar effects on measures

of lung function, quality of life, and peak exercise capacity. In a similar study, van der Giessen and colleagues (2007) also found that the regimens had non-significant differences in most measures of lung function. However, as their primary outcome, they included an additional measure: maximal expiratory flow at 25% of the forced vital capacity (FVC). This outcome was significantly better when dornase alpha was administered before physical airway clearance techniques. Wilson and colleagues (2007) performed a similar study in adults and children with cystic fibrosis and found no significant differences for most outcomes. However, in those outcomes that did differ (ie, forced expiratory flow rate between 25% What is already known on this topic: The timing of dornase alpha in relation to physiotherapy techniques may alter the effect of these two interventions on airway clearance. However, this has not been examined in adults with cystic fibrosis.