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.

DESIGN: Determination of transportability in frog palate and viscoelasticity in vitro.

SETTING: Research laboratory at a medical centre. Patients: Sputa from 15 patients with CF, chronically infected with Pseudomonas aeruginosa, were studied.

INTERVENTIONS: 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 µM) 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.