Aerosolized dornase alfa (rhDNase) for therapy of cystic fibrosis

Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 2):S70-4. doi: 10.1164/ajrccm/151.3_Pt_2.S70.


The major causes of morbidity and mortality in cystic fibrosis (CF) are the obstruction and damaged airways that result from the accumulation of viscid and infected secretions. Dornase alfa, also called recombinant human DNase I (rhDNase), cleaves extracellular DNA, which is present in inordinately high concentrations in purulent CF airway secretions. Dornase alfa has been found to increase the pourability and reduce the viscoelasticity of CF sputum in vitro and, in an animal model, to increase its mucociliary transportability. Short-term (10-day) Phase I and II clinical trials showed dornase alfa to be safe and effective in improving pulmonary function in clinically stable CF patients with mild to moderate pulmonary disease (FVC > or = 40% of predicted value). A long-term (24-week) Phase IIB clinical trial demonstrated the importance of administering dornase alfa daily to maintain its efficacy. A large-scale, long-term, Phase III clinical trial, consisting of a 24-week double-blind period and a 24-week open-label extension, confirmed these findings and further demonstrated that dornase alfa reduces the incidence of respiratory tract infectious exacerbations requiring parenteral antibiotic therapy. Dornase alfa also decreased the rate of hospitalizations, the number of days missed from work or school, and the frequency of CF-related symptoms. Adverse events were limited to upper airway irritation (i.e., voice alteration, laryngitis, pharyngitis), rash, chest pain, and conjunctivitis. These manifestations generally were mild and transient, and they did not limit the use of dornase alfa. A small proportion (2 to 4%) of patients developed serum antibodies to dornase alfa, but no patient developed anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aerosols
  • Animals
  • Clinical Trials as Topic
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • DNA / drug effects
  • Deoxyribonuclease I / administration & dosage
  • Deoxyribonuclease I / adverse effects
  • Deoxyribonuclease I / pharmacology
  • Deoxyribonuclease I / therapeutic use*
  • Disease Models, Animal
  • Double-Blind Method
  • Expectorants / adverse effects
  • Expectorants / therapeutic use
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Mucociliary Clearance / drug effects
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Sputum / drug effects


  • Aerosols
  • Expectorants
  • Recombinant Proteins
  • DNA
  • DNASE1 protein, human
  • Deoxyribonuclease I