Effect of nebulised recombinant DNase on neutrophil elastase load in cystic fibrosis.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
This study indicates that prolonged daily administration of rhDNase results in a reduction in elastase load in patients with cystic fibrosis.
Costello
C M
CM
Department of Medicine and Therapeutics, University College Dublin, Ireland.
O'Connor
C M
CM
Finlay
G A
GA
Shiels
P
P
FitzGerald
M X
MX
Hayes
J P
JP
D000293:Adolescent; D000328:Adult; D000336:Aerosols; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D019272:Leukocyte Elastase; D008297:Male; D010196:Pancreatic Elastase / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013183:Sputum / Q000201:enzymology; D014797:Vital Capacity / Q000187:drug effects
D000336:Aerosols; D016209:Interleukin-8; D011994:Recombinant Proteins; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase