通过控制吸入而改善囊性纤维化患者对α链道酶治疗的应答

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 2.5mL 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 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 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.