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Previous Volume 331:637-642 September 8, 1994 Number 10 Next

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ABSTRACT

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. .

Source Information

From the Department of Medical Affairs, Genentech, Inc., South San Francisco (H.J.F., D.H.C., M.L.N.); the Children's Hospital of Buffalo, Buffalo, N.Y. (D.S.B.); G.H. Besselaar Associates, Princeton, N.J. (E.M.M.); Children's Hospital and Medical Center of Seattle, Seattle (B.W.R., A.L.S.); Johns Hopkins University, Baltimore (B.J.R); the Pulmozyme Study Group, and Children's Hospital, Boston (M.E.W.). The members of the Pulmozyme Study Group and the participating institutions are listed in the Appendix.

Address reprint requests to Dr. Fuchs at Genentech, Inc., 460 Point San Bruno Blvd., South San Francisco, CA 94080.

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N Engl J Med 1995; 332:123-125, Jan 12, 1995. Correspondence

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