Improved clearability of cystic fibrosis sputum with dextran treatment in vitro.
Most patients with cystic fibrosis (CF) are infected by Pseudomonas aeruginosa. Dextran exhibits anti-adhesive effects in preventing attachment of P. aeruginosa to epithelial cells (1). 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 degrees 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.
Feng
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Pulmonary Research Group, University of Alberta, Edmonton, Canada.
Garrett
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H
Speert
D P
DP
King
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D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001001:Anura; D001422:Bacterial Adhesion / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003371:Cough / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000382:microbiology / Q000503:physiopathology*; D003911:Dextrans / Q000494:pharmacology*; D004285:Dogs; D004548:Elasticity; D004847:Epithelial Cells / Q000382:microbiology; D005069:Evaluation Studies as Topic; D006801:Humans; D066298:In Vitro Techniques; D007552:Isotonic Solutions; D008280:Magnetics; D009079:Mucociliary Clearance / Q000187:drug effects; D009093:Mucus / Q000187:drug effects; D010159:Palate / Q000187:drug effects / Q000502:physiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012212:Rheology; D000077331:Ringer's Solution; D012965:Sodium Chloride; D013183:Sputum / Q000502:physiology*; D013501:Surface-Active Agents / Q000494:pharmacology*; D014783:Viscosity
D003911:Dextrans; D007552:Isotonic Solutions; D013501:Surface-Active Agents; D012965:Sodium Chloride; D000077331:Ringer's Solution