Effect of treatment with dornase alpha on airway inflammation in patients with cystic fibrosis.
Recombinant human deoxyribonuclease (rhDNase) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis (CF), but its long-term effect on airway inflammation remains unknown. In this study, we used bronchoalveolar lavage (BAL) to investigate the long-term effect of rhDNase on inflammation in patients with CF having mild lung disease. A total of 105 patients with CF (> or =5 years of age) having normal lung function were randomized to receive rhDNase (2.5 mg/day) or no rhDNase. Patients with a normal percentage of neutrophils in BAL fluid at baseline were not randomized and served as the control group. The percentage of neutrophils in the pooled BAL sample was similar in both randomized groups at baseline. A significant increase in neutrophils was observed over the 3-year study period in both untreated patients and control subjects, whereas neutrophils remained unchanged in patients treated with rhDNase. Elastase activities and interleukin-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase. We conclude that in patients with CF, an increase in neutrophilic airway inflammation is found that is positively influenced by rhDNase treatment.
Paul
Karl
K
Department of Pediatric Pneumology and Immunology, Charité, Germany.
Rietschel
Ernst
E
Ballmann
Manfred
M
Griese
Matthias
M
Worlitzsch
Dieter
D
Shute
Janis
J
Chen
Christiane
C
Schink
Tanja
T
Döring
Gerd
G
van Koningsbruggen
Silke
S
Wahn
Ulrich
U
Ratjen
Felix
F
D000293:Adolescent; D000328:Adult; D018893:Bronchoalveolar Lavage; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology*; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D009504:Neutrophils; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors
D016209:Interleukin-8; D011994:Recombinant Proteins; D009195:Peroxidase; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D019272:Leukocyte Elastase