Journal Article


J P Hayes
M X Fitzgerald
P Shiels
G A Finlay
C M O'Connor
C M Costello



adult dnase1 protein human pharmacology metabolism humans cystic fibrosis adolescent vital capacity leukocyte elastase forced expiratory volume drug effects sputum deoxyribonuclease i female recombinant proteins therapeutic use drug administration schedule physiopathology interleukin 8 pancreatic elastase aerosols enzymology drug therapy male

Effect of nebulised recombinant DNase on neutrophil elastase load in cystic fibrosis. (1996)

Abstract DNA released by degenerating inflammatory neutrophils contributes to mucous plugging of airways in patients with cystic fibrosis. Neutrophil elastase, a major effector of tissue destruction in the lungs of patients with cystic fibrosis, is a highly cationic molecule which is bound and inhibited by negatively charged polyanions such as mucin and DNA in purulent sputum. Thus, the solubilisation of DNA in the airways by aerosolised recombinant DNase may remove a source of neutrophil elastase inhibition, effectively increasing elastase load. The aim of this study was to assess the effect of rhDNase therapy on neutrophil elastase load in patients with cystic fibrosis. Blood and sputum were collected from 15 patients with cystic fibrosis before initiation of nebulised DNase therapy and at 12 weeks following therapy. The long term effects of continuous rhDNase administration were evaluated at 52 weeks for 11 of these patients. Plasma was analysed for neutrophil elastase, interleukin (IL)-8 and neutrophil elastase in complex with alpha 1-protease inhibitor (alpha 1PI). Sputum was assessed for neutrophil elastase, IL-8, and active elastase. At each visit spirometric measurements were carried out. Sputum elastase activity decreased at 12 weeks and was maintained at 52 weeks when a decline in total plasma elastase was also observed. Although, as expected, there was a correlation between plasma levels of total elastase and neutrophil elastase/alpha 1PI complex, the decrease in the levels of the complex at 52 weeks did not reach statistical significance. This study indicates that prolonged daily administration of rhDNase results in a reduction in elastase load in patients with cystic fibrosis.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

J P Hayes, M X Fitzgerald, P Shiels, G A Finlay, C M O'Connor, C M Costello

Experts in our system

Jer Hayes
Dublin City University
Total Publications: 25
Michael Fitzgerald
Trinity College Dublin
Total Publications: 101
C M O'Connor
University College Dublin
Total Publications: 43