title: DNA concentrations in BAL fluid of cystic fibrosis patients with early lung disease: influence of treatment with dornase alpha.
abstract: Recombinant DNase (dornase alpha) was shown to improve lung function and reduce pulmonary exacerbations in cystic fibrosis (CF) patients, but its effects on DNA concentrations in the lower airways remain unclear at the present time. As part of the Bronchoalveolar Lavage in the Evaluation of Anti-Inflammatory Treatment (BEAT) Study, a multicenter open study to evaluate the evolution of inflammation in CF patients with early lung disease and its modulation by dornase alpha treatment, we studied DNA concentrations in the bronchoalveolar lavage (BAL) fluid of 48 CF patients with mild lung disease. After the initial BAL, 29 patients received daily treatment with 2.5 mg of dornase alpha; 19 patients served as controls. BAL was repeated after 18 months in all patients. Mean BAL fluid DNA concentrations were not different between groups at baseline (mean +/- SD, 14.1 +/- 6.9 microg/ml for controls, and 17.6 +/- 11.2 microg/ml for the dornase alpha group), but higher than previously reported for infants with CF. A weak but positive correlation (P <0.01) was observed between the percentage of neutrophils in BAL fluid and DNA levels. On reassessment after 18 months, the percentage of neutrophils was not different between the two groups, but DNA had increased in controls, whereas decreased levels were observed in treated patients (P <0.03, t-test). DNA concentrations increased by more than 10 microg/ml in 7 of 19 controls compared to 2 of 29 CF patients treated with rhDNase (P=0.01, Fisher's test). Therefore, treatment with dornase alpha over 18 months reduces DNA load in BAL fluid, which may have a positive effect on the clearance of lower airway secretions.
authors.affiliation: Children's Hospital, University of Essen, Essen, Germany. f.ratjen@uni-essen.de
authors.forename: F
authors.initials: F
authors.lastname: Ratjen
authors.forename: K
authors.initials: K
authors.lastname: Paul
authors.forename: S
authors.initials: S
authors.lastname: van Koningsbruggen
authors.forename: S
authors.initials: S
authors.lastname: Breitenstein
authors.forename: E
authors.initials: E
authors.lastname: Rietschel
authors.forename: W
authors.initials: W
authors.lastname: Nikolaizik
mesh_terms: D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics; D004247:DNA / Q000032:analysis*; D003850:Deoxyribonuclease I / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D004247:DNA; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I