title: Small airway deposition of dornase alfa during exacerbations in cystic fibrosis; a randomized controlled clinical trial.
abstract: BACKGROUND
  Small airway obstruction is important in the pathophysiology of cystic fibrosis (CF) lung disease. Additionally, many CF patients lose lung function in the long term as a result of respiratory tract exacerbations (RTEs). No trials have been performed to optimize mucolytic therapy during a RTE. We investigated whether specifically targeting dornase alfa to the small airways improves small airway obstruction during RTEs.
  
  
  METHODS
  In a multi-center, double-blind, randomized controlled trial CF patients hospitalized for a RTE and on maintenance treatment with dornase alfa were switched to a smart nebulizer. Patients were randomized to small airway deposition (n = 19) or large airway deposition (n = 19) of dornase alfa for at least 7 days. Primary endpoint was forced expiratory flow at 75% of forced vital capacity (FEF75 ).
  
  
  RESULTS
  Spirometry parameters improved significantly during admission, but the difference in mean change in FEF75 between treatment groups was not significant: 0.7 SD, P = 0.30. FEF25-75 , FEV1 , nocturnal oxygen saturation and diary symptom scores also did not differ between groups.
  
  
  CONCLUSIONS
  This study did not detect a difference if inhaled dornase alfa was targeted to small versus large airways during a RTE. However, the 95% confidence interval for the change in FEF75 was wide. Further studies are needed to improve the effectiveness of RTE treatment in CF.
authors.affiliation: Department of Paediatric Pulmonology and Allergology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: Bakker
authors.forename: S
authors.initials: S
authors.lastname: Volpi
authors.forename: E
authors.initials: E
authors.lastname: Salonini
authors.forename: B
authors.initials: B
authors.lastname: Müllinger
authors.forename: P
authors.initials: P
authors.lastname: Kroneberg
authors.forename: M
authors.initials: M
authors.lastname: Bakker
authors.forename: W C J
authors.initials: WC
authors.lastname: Hop
authors.forename: B M
authors.initials: BM
authors.lastname: Assael
authors.forename: H A W M
authors.initials: HA
authors.lastname: Tiddens
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000008:administration & dosage* / Q000627:therapeutic use; D018450:Disease Progression; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013147:Spirometry; D016896:Treatment Outcome; D014797:Vital Capacity; D055815:Young Adult
chemical_list: D000336:Aerosols; D005100:Expectorants; D011994:Recombinant Proteins; D003850:Deoxyribonuclease I; C568813:dornase alfa
keywords: aerosol; nebulizer; nocturnal oxygen saturation; respiratory tract exacerbation; spirometry