Am. J. Respir. Crit. Care Med.,
Volume 157, Number 3, March 1998, 710-714
Improved Clearability of Cystic Fibrosis Sputum
with Dextran Treatment in vitro
WEI
FENG,
HEATHER
GARRETT,
DAVID P.
SPEERT,
and
MALCOLM
KING
Pulmonary Research Group, University of Alberta, Edmonton; and Department of Paediatrics, University of British Columbia,
Vancouver, British Columbia, Canada
Most patients with cystic fibrosis (CF) are infected by Pseudomonas aeruginosa. Dextran exhibits antiadhesive effects in preventing attachment of P. aeruginosa to epithelial cells (). The initial purpose
of this study was to evaluate the potential of dextran to alter the rheology and ciliary transportability
of CF sputum prior to initiation of a clinical trial in patients with CF. Sputum samples were collected
from 25 patients with CF not receiving rhDNase therapy for use in in vitro testing. Aliquots of CF sputum were treated with 10% vol. Ringer's or the same volume of Dextran 4000 to give a final concentration of 0.4% (4 mg/ml) or 4% (40 mg/ml) dextran in the sputum. Dog mucus samples were collected from seven healthy, anesthetized dogs from the endotracheal tube cuff. Aliquots of dog mucus
were subjected to the same concentrations of dextran as the CF sputum. All treated samples were incubated for 30 min at 37° C, and their rheologic properties (viscoelasticity) were evaluated by magnetic microrheometry. For 17 of the sputum samples, frog palate mucociliary transportability was determined from sputum movement on the ciliated, mucus-depleted frog palate, relative to native frog
mucus control. Spinnability (cohesiveness) was evaluated by the filancemeter technique for eight
sputum samples. Overall, whether for CF sputum or healthy dog mucus, Dextran 4000 treatment significantly reduced viscoelasticity and increased predicted mucociliary and cough clearability. Direct
measurements of sputum mucociliary clearability on frog palate increased significantly with 0.4%
dextran and 4% dextran compared with saline control. Sputum spinnability (cohesiveness) decreased
significantly with both dextran concentrations, too. The effects on viscoelasticity and spinnability
were greater at 4% than at 0.4%. There was a significant positive correlation between spinnability
and viscoelasticity, and negative relationships between spinnability and both forms of clearability as
predicted from viscoelastic measurements. This study suggests that treatment with Dextran 4000 can
reduce the crosslink density and cohesiveness of CF and improve mucociliary and cough clearability.
Dextran 4000 is an inexpensive and nontoxic agent that may be of benefit in patients with CF lung
disease and perhaps in other respiratory disease where mucus retention is an important feature.
