Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group.
BACKGROUND
Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick, purulent secretions, which results in recurrent, symptomatic exacerbations. The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I (rhDNase), a bioengineered copy of the human enzyme.


METHODS
We performed a randomized, double-blind, placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function. A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as outpatients.


RESULTS
One or more exacerbations occurred in 27 percent of the patients given placebo, 22 percent of those treated with rhDNase once daily, and 19 percent of those treated with rhDNase twice daily. As compared with placebo, the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent (P = 0.04) and 37 percent (P < 0.01), respectively. The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean (+/- SD) of 5.8 +/- 0.7 and 5.6 +/- 0.7 percent, respectively. None of the patients had anaphylaxis. Voice alteration and laryngitis were more frequent in the rhDNase-treated patients than in those receiving placebo but were rarely severe and resolved within 21 days of onset.


CONCLUSIONS
In patients with cystic fibrosis, the administration of rhDNase reduced but did not eliminate exacerbations of respiratory symptoms, resulted in slight improvement in pulmonary function, and was well tolerated.
Fuchs
H J
HJ
Department of Medical Affairs, Genentech, Inc., South San Francisco, CA 94080.
Borowitz
D S
DS
Christiansen
D H
DH
Morris
E M
EM
Nash
M L
ML
Ramsey
B W
BW
Rosenstein
B J
BJ
Smith
A L
AL
Wohl
M E
ME
D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000402:Airway Obstruction / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D003850:Deoxyribonuclease I / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005100:Expectorants / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014797:Vital Capacity
D000336:Aerosols; D005100:Expectorants; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I