Am. J. Respir. Crit. Care Med., Vol 154, No. 2, 08 1996, 413-417.
Short-term recombinant human DNase in bronchiectasis. Effect on clinical state and in vitro sputum transportability
PJ Wills, T Wodehouse, K Corkery, K Mallon, R Wilson and PJ Cole
Host Defence Unit, Royal Brompton National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
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.
