Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability.
We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation. The outcome measures were spirometry, subjective quality of life/dyspnea, and safety. We also measured the ciliary transportability of the sputum expectorated before and after the treatment period, using the mucus-depleted bovine trachea. The drug was well tolerated, but it produced no significant change in any of the outcome variables or in sputum transportability. When the drug was incubated with bronchiectatic sputum in vitro, a fall in transportability was observed. We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population, which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design.
Wills
P J
PJ
Host Defence Unit, Royal Brompton National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Wodehouse
T
T
Corkery
K
K
Mallon
K
K
Wilson
R
R
Cole
P J
PJ
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000368:Aged; D000818:Animals; D001987:Bronchiectasis / Q000188:drug therapy*; D002417:Cattle; D003850:Deoxyribonuclease I / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005100:Expectorants / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009079:Mucociliary Clearance / Q000187:drug effects*; D009093:Mucus / Q000187:drug effects; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013183:Sputum / Q000187:drug effects; D013997:Time Factors; D014132:Trachea / Q000187:drug effects; D016896:Treatment Outcome
D000336:Aerosols; D005100:Expectorants; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I