title: Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation.
abstract: 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 (FEF(75%)). FEF(75%) 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 show a 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 FEF(75%) Z-score and a significant difference (p = 0.04) between groups in absolute FEF(75%) (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 FEF(75%) in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition.
authors: Dept of Paediatric Pulmonology and Allergology, Erasmus MC – Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: E M
authors: EM
authors: Bakker
authors: S
authors: S
authors: Volpi
authors: E
authors: E
authors: Salonini
authors: E C
authors: EC
authors: van der Wiel-Kooij
authors: C J J C M
authors: CJ
authors: Sintnicolaas
authors: W C J
authors: WC
authors: Hop
authors: B M
authors: BM
authors: Assael
authors: P J F M
authors: PJ
authors: Merkus
authors: H A W M
authors: HA
authors: Tiddens
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy*; D003850:Deoxyribonuclease I / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010349:Patient Compliance; D012129:Respiratory Function Tests; D016896:Treatment Outcome
chemical_list: D005100:Expectorants; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I