title: Timing of dornase alfa inhalation for cystic fibrosis.
abstract: BACKGROUND
  Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane review.
  
  
  OBJECTIVE
  To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day).
  
  
  METHODS
  Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the most recent search: 25 April 2016.
  
  
  METHODS
  Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation.
  
  
  METHODS
  Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed.
  
  
  RESULTS
  We identified 115 trial reports representing 55 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second. Similarly, forced vital capacity and quality of life were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small studies in children (seven to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial, morning versus evening inhalation had no impact on lung function or symptoms.
  
  
  CONCLUSIONS
  The current evidence derived from a small number of participants does not indicate that inhalation of dornase alfa after airway clearance techniques is more or less effective than the traditional recommendation to inhale nebulised dornase alfa 30 minutes prior to airway clearance techniques, for most outcomes. For children with well-preserved lung function, inhalation before airway clearance may be more beneficial for small airway function than inhalation after. However, this result relied on a measure with high variability and studies with variable follow up. In the absence of strong evidence to indicate that one timing regimen is better than another, the timing of dornase alpha inhalation can be largely based on pragmatic reasons or individual preference with respect to the time of airway clearance and time of day. Further research is warranted.
authors.affiliation: Department of Respiratory Medicine, Royal Prince Alfred Hospital, Level 11, E Block, Missenden Road, Camperdown, New South Wales, Australia, NSW 2050.
authors.forename: Ruth
authors.initials: R
authors.lastname: Dentice
authors.forename: Mark
authors.initials: M
authors.lastname: Elkins
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D002648:Child; D003131:Combined Modality Therapy / Q000379:methods; D003550:Cystic Fibrosis / Q000628:therapy*; D003850:Deoxyribonuclease I / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D006801:Humans; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage; D012138:Respiratory Therapy / Q000379:methods*; D013997:Time Factors; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D003850:Deoxyribonuclease I; C568813:dornase alfa