title: The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis.
abstract: Outcome measures to assess therapeutic interventions in cystic fibrosis (CF) patients with mild lung disease are lacking. Our aim was to determine if the lung clearance index (LCI) can detect a treatment response to dornase alfa in paediatric CF patients with normal spirometry. CF patients between 6-18 yrs of age with FEV(1 )≥ 80% pred were eligible. In a crossover design, 17 patients received 4 weeks of dornase alfa and placebo in a randomised sequence separated by a 4-week washout period. The primary end-point was the change in LCI from dornase alfa versus placebo. A mixed model approach incorporating period-dependent baselines was used. The mean ± sd age was 10.32 ± 3.35 yrs. Dornase alfa improved LCI versus placebo (0.90 ± 1.44; p = 0.022). Forced expiratory flow at 25-75% expired volume measured by % pred and z-scores also improved in subjects on dornase alfa (6.1% ± 10.34%; p = 0.03 and 0.28 ± 0.46 z-score; p = 0.03). Dornase alfa significantly improved LCI. Therefore the LCI may be a suitable tool to assess early intervention strategies in this patient population.
authors.affiliation: Division of Respiratory Medicine, Dept of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada. reshma.amin@sickkids.ca
authors.forename: R
authors.initials: R
authors.lastname: Amin
authors.forename: P
authors.initials: P
authors.lastname: Subbarao
authors.forename: W
authors.initials: W
authors.lastname: Lou
authors.forename: A
authors.initials: A
authors.lastname: Jabar
authors.forename: S
authors.initials: S
authors.lastname: Balkovec
authors.forename: R
authors.initials: R
authors.lastname: Jensen
authors.forename: S
authors.initials: S
authors.lastname: Kerrigan
authors.forename: P
authors.initials: P
authors.lastname: Gustafsson
authors.forename: F
authors.initials: F
authors.lastname: Ratjen
mesh_terms: D000293:Adolescent; D016956:Burkholderia cepacia / Q000378:metabolism; D002648:Child; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy*; D003850:Deoxyribonuclease I / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D010919:Placebos; D012107:Research Design; D012129:Respiratory Function Tests; D013147:Spirometry / Q000379:methods; D013997:Time Factors; D014691:Ventilation
chemical_list: D010919:Placebos; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I