Better treatment of obstructed small airways is needed in cystic fibrosis. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. In a multicentre, double-blind, randomised controlled clinical trial, cystic fibrosis patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser and randomised to small airway deposition (n=24) or large airway deposition (n=25) for 4 weeks. The primary outcome parameter was forced expiratory flow at 75% of forced vital capacity (FEF75%). FEF75% increased significantly by 0.7 SD (5.2% predicted) in the large airways group and 1.2 SD (8.8%pred) in the small airways group. Intention-to-treat analysis did not showa significant difference in treatment effect between groups. Per-protocol analysis, excluding patients not completing the trial or with adherence <70%, showed a trend (p=0.06) in FEF75% Z-score and a significant difference (p=0.04) between groups in absolute FEF75% (L·s-1) favouring small airway deposition. Improved delivery of dornase alfa using a smart nebuliser that aids patients in correct inhalation technique resulted in significant improvement of FEF75% in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition. Copyright

Aerosol deposition, Inhaled drug delivery, Nebuliser, Paediatric, Small airways
dx.doi.org/10.1183/09031936.00006211, hdl.handle.net/1765/33991
The European Respiratory Journal
Erasmus MC: University Medical Center Rotterdam

van den Beukel-Bakker, E.M, Volpi, S, Salonini, E, van der Wiel-Kooij, E.C, Sintnicolaas, C.J.J.C.M, Hop, W.C.J, … Tiddens, H.A.W.M. (2011). Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation. The European Respiratory Journal, 38(6), 1328–1335. doi:10.1183/09031936.00006211