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Published ahead of print on December 18, 2003, doi:10.1164/rccm.200307-959OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 6, March 2004, 719-725

A more recent version of this article appeared on March 15, 2004
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Submitted on July 15, 2003
Accepted on December 15, 2003

Effect of treatment with dornase alpha on airway inflammation in cystic fibrosis patients

Karl Paul1, Ernst Rietschel2, Manfred Ballmann3, Matthias Griese4, Dieter Worlitzsch5, Janis Shute6, Christiane Chen1, Tanja Schink7, Gerd Doring5, Silke van Konigsbruggen2, Ulrich Wahn1, and Felix Ratjen8*

1 Pediatric Pneumology and Immunology, Charite, Homboldt University, Berlin, Germany, 2 Pediatric Pneumology and Allergology, Children's Hospital, University of Cologne, Cologne, Germany, 3 Pediatric Pneumology, Medical School, University of Hannover, Hannover, Germany, 4 Children's Hospital, University of Munich, Munich, Germany, 5 Institute of General and Environmental Hygiene, University of Tubingen, Tubingen, Germany, 6 School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom, 7 Medical Biometry, Humboldt-University, Berlin, Germany, 8 Children's Hospital, University of Essen, Essen, Germany

* To whom correspondence should be addressed. E-mail: f.ratjen{at}uni.essen.de.

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 CF patients with mild lung disease. 105 CF patients >= 5 years of age with 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 a 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 controls, whereas neutrophils remained unchanged in patients treated with rhDNase. Elastase activities and IL-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase. We conclude that an increase in neutrophilic airway inflammation is found in patients with cystic fibrosis that is positively influenced by rhDNase treatment.
Key words: rhDNase, bronchoalveolar lavage, cystic fibrosis, airway inflammation, lung function




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