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Effect of Treatment with Dornase Alpha on Airway Inflammation in Patients with Cystic Fibrosis

Department of Pediatric Pneumology and Immunology, Charité; Department of Medical Biometry, Humboldt-University, Berlin; Department of Pediatric Pneumology and Allergology, Children's Hospital, University of Cologne, Cologne; Department of Pediatric Pneumology, Medical School, University of Hannover, Hannover; Children's Hospital, University of Munich, Munich; Institute of General and Environmental Hygiene, University of Tübingen, Tübingen; Children's Hospital, University of Essen, Essen, Germany; and School of Pharmacy and Biomedical Sciences, University of Portsmouth, United Kingdom

Correspondence and requests for reprints should be addressed to Felix Ratjen, M.D., Children's Hospital, University of Essen, Hufeland Strasse 55, D-45122 Essen, Germany. E-mail: f.ratjen{at}uni-essen.de

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 ( 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.

Key Words: recombinant human deoxyribonuclease • bronchoalveolar lavage • cystic fibrosis • airway inflammation • lung function

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