Additive effect of dornase alfa and Nacystelyn on transportability and viscoelasticity of cystic fibrosis sputum.
OBJECTIVE
To investigate the effect of dornase alfa (DA), Nacystelyn (NAL) and their combination on mucociliary transportability and mucus viscoelasticity of cystic fibrosis (CF) sputum, and to assess whether the combination possesses an additive effect.


METHODS
Determination of transportability in frog palate and viscoelasticity in vitro.


METHODS
Research laboratory at a medical centre.


METHODS
Sputa from 15 patients with CF, chronically infected with Pseudomonas aeruginosa, were studied.


METHODS
Sputum samples were incubated without any drug solution as a control, and with normal saline, DA, NAL and a mixture of DA and NAL in concentrations approximating those achieved in clinical practice.


RESULTS
Normal saline (10% volume) by itself had a small effect on CF sputum transportability with a mean increase of 9%, and on viscoelasticity with a mean of decrease of 0.22 log units, respectively, compared with control (incubation without saline). DA (200 nM) further increased the transportability by a mean of 35% versus saline and decreased viscoelasticity by a mean of 0.30 log units. NAL (100 M) increased the transportability by a mean of 32% and decreased viscoelasticity by a mean of 0.22 log units from the levels achieved with saline. The mixture of DA plus NAL at one-half of the above concentration of each agent produced an additional increase in the transportability, by a mean of 18%, and a further decrease in viscoelasticity, by a mean of 0.25 log units, compared with DA or NAL as a single treatment.


CONCLUSIONS
The combination of DA and NAL exhibits an additive effect for both the viscoelasticity and transportability of CF sputum samples. The two agents appear to act well together in breaking down the bonding due to extracellular DNA and mucins. Clinical studies should be undertaken to see whether the additive combination at lower concentration produces the anticipated benefits of improved airway clearance and fewer side effects.
Sun
Feng
F
Pulmonary Research Group, 173 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Tai
Shusheng
S
Lim
Thomas
T
Baumann
Ulrich
U
King
Malcolm
M
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001692:Biological Transport / Q000187:drug effects; D002648:Child; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy*; D003850:Deoxyribonuclease I / Q000494:pharmacology*; D004347:Drug Interactions; D004548:Elasticity / Q000187:drug effects; D005260:Female; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D009093:Mucus / Q000187:drug effects; D011336:Probability; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D012016:Reference Values; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D013183:Sputum / Q000187:drug effects* / Q000382:microbiology; D014783:Viscosity / Q000187:drug effects
C086501:N-acetylcysteine lysinate; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D008239:Lysine; D000111:Acetylcysteine