Effects of rhDNase on purulent airway secretions in chronic bronchitis.
Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce in vitro the viscosity and to improve the transport capacity of purulent respiratory mucus in cystic fibrosis. During episodes of exacerbation of chronic bronchitis, the patients generally expectorate purulent mucus. Purulence of mucus is associated with an increased deoxyriboneucleic acid (DNA) concentration. We analyzed in vitro the potential effect of rhDNase on chronic bronchitis mucus transport by the ciliary activity (frog palate model) and by simulated cough (cough machine model), as well as the effect on mucus viscosity (controlled stress rheometer) and surface properties (contact angle). Purulent sputa collected from patients with chronic bronchitis (n = 15) during an episode of exacerbation were incubated for 30 min at 37 degrees C with either rhDNase at two different concentrations (final concentration 2 or 4 micrograms.mL-1) or placebo. The median mucociliary transport rate was significantly improved by rhDNase from 0.68 with placebo to 0.79 and 0.83 with 2 and 4 micrograms.mL-1 of rhDNase, respectively. A significant improvement in mucus cough transport was also induced by rhDNase from 25.5 mm with placebo to 27.0 mm with either 2 or 4 micrograms.mL-1 rhDNase. These improvements in mucus transport capacity were associated with alterations in the physical properties of the mucus. The mucus median control viscosity (511.4 Pa.s) and median contact angle (0.85 rd) significantly decreased to 112.5 Pa.s and 0.74 rd, respectively, in the presence of 4 micrograms.mL-1 of rhDNase. These findings demonstrate that recombinant deoxyribonuclease may exert a beneficial effect on mucus clearance in vitro by altering the viscosity and surface properties of the purulent chronic bronchitic sputum samples.
Puchelle
E
E
Unité INSERM 314, Université de Reims, France.
Zahm
J M
JM
de Bentzmann
S
S
Grosskopf
C
C
Shak
S
S
Mougel
D
D
Polu
J M
JM
D001991:Bronchitis / Q000378:metabolism*; D002908:Chronic Disease; D003371:Cough / Q000378:metabolism; D004247:DNA / Q000032:analysis; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009079:Mucociliary Clearance / Q000502:physiology; D009093:Mucus / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D013499:Surface Properties; D014783:Viscosity
D011994:Recombinant Proteins; D004247:DNA; D003851:Deoxyribonucleases