title: Clinical use of dornase alpha is associated with a slower rate of FEV1 decline in cystic fibrosis.
abstract: OBJECTIVE
  Randomized controlled trials of dornase alpha have shown forced expiratory volume in 1 sec (FEV(1) ) to improve in patients with cystic fibrosis (CF) but have not assessed change in the rate of lung function decline. We assessed the relationship of dornase alpha use and FEV(1) decline using the Epidemiologic Study of Cystic Fibrosis (ESCF).
  
  
  METHODS
  Patients aged 8-38 years who had been enrolled in ESCF for 2 years when initially treated with dornase alpha were selected if they remained on treatment during the following 2 years. A comparator group included patients aged 8-38 who were not yet reported to have received dornase alpha. For each patient we estimated the annual rate of decline in FEV(1) % predicted before and after the index using a mixed-effects model adjusted for age, gender, pulmonary exacerbations, respiratory therapies, and nutritional supplements.
  
  
  RESULTS
  The dornase alpha group (n = 2,230) had a lower FEV(1) % predicted at index and a more rapid decline during the pre-index period. The mean rate of FEV(1) decline improved for the dornase alpha group; the improvement was similar in adults and children 8-17 years old but was not statistically significant in adults. The comparator group (n = 5,970) showed no change among adults and an increased rate of decline among children 8-17 years old.
  
  
  CONCLUSIONS
  The use of dornase alpha for a 2-year period is associated with a reduction in the rate of FEV(1) decline. These results also demonstrate the value of using an observational study to assess the association of instituting new therapies in the clinical setting with changes in the rate of FEV(1) decline in patients with CF.
authors: Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. michael.konstan@case.edu
authors: Michael W
authors: MW
authors: Konstan
authors: Jeffrey S
authors: JS
authors: Wagener
authors: David J
authors: DJ
authors: Pasta
authors: Stefanie J
authors: SJ
authors: Millar
authors: Joan R
authors: JR
authors: Jacobs
authors: Ashley
authors: A
authors: Yegin
authors: Wayne J
authors: WJ
authors: Morgan
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology*; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I