Effect ofnebulised recombinant DNaseon neutrophil elastase loadincystic fibrosis

Background - DNA released by degenerating inflammatory neutrophils contributes tomucousplugging ofairways in patients withcystic fibrosis. Neutrophil elastase, a majoreffector oftissue destruction inthelungsofpatients with cysticfibrosis, is a highlycationic moleculewhichisboundandinhibited bynegatively charged polyanions suchas mucinand DNA inpurulent sputum. Thus,thesolubilisation ofDNA inthe airwaysby aerosolised recombinant DNasemayremoveasourceofneutrophil elastase inhibition, effectively increasing elastase load. Theaimofthisstudy wasto assesstheeffect ofrhDNasetherapy on neutrophil elastase loadinpatients with cystic fibrosis. Methods- Bloodandsputumwerecollected from15patients withcystic fibrosis before initiation ofnebulised DNasetherapyandat12weeksfollowing therapy. The longtermeffects ofcontinuous rhDNase administration wereevaluated at52weeks for11ofthesepatients. Plasmawasanalysedforneutrophil elastase, interleukin (IL)-8 andneutrophil elastase incomplex witha,-protease inhibitor (aIPI). Sputum wasassessed forneutrophil elastase, IL-8, andactive elastase. Ateachvisit spirometricmeasurements werecarried out. Results - Sputumelastase activity decreased at12weeksandwasmaintained at52weekswhenadecline intotal plasma elastase wasalsoobserved. Although, as expected, therewasacorrelation between plasmalevels oftotal elastase andneutrophilelastase/alPI complex, thedecrease in thelevels ofthecomplex at52weeksdid notreachstatistical significance. Conclusions - Thisstudyindicates that prolongeddailyadministration of rhDNaseresults inareduction inelastase loadinpatients withcystic fibrosis. (Thorax 1996;51:619-623)