A new paradigm in respiratory hygiene: modulating respiratory secretions to contain cough bioaerosol without affecting mucus clearance.
BACKGROUND
Several strategies and devices have been designed to protect health care providers from acquiring transmissible respiratory diseases while providing care. In modulating the physical characteristics of the respiratory secretions to minimize the aerosolization that facilitates transmission of airborne diseases, a fundamental premise is that the prototype drugs have no adverse effect on the first line of respiratory defense, clearance of mucus by ciliary action.


METHODS
To assess and demonstrate the primary mechanism of our mucomodulators (XLs), we have built our evidence moving from basic laboratory studies to an ex-vivo model and then to an in-vivo large animal model. We exposed anesthetized dogs without hypersecretion to different dose concentrations of aerosolized XL "B", XL "D" and XL "S". We assessed: cardio-respiratory pattern, tracheal mucus clearance, airway patency, and mucus viscoelastic changes.


RESULTS
Exposure of frog palate mucus to XLs did not affect the clearance of mucus by ciliary action. Dogs maintained normal cardio-respiratory pattern with XL administration. Tracheal mucociliary clearance in anesthetized dogs indicated a sustained 40% mean increase. Tracheal mucus showed increased filance, and there was no mucus retention in the airways.


CONCLUSIONS
The ex-vivo frog palate and the in-vivo mammalian models used in this study, appear to be appropriate and complement each other to better assess the effects that our mucomodulators exert on the mucociliary clearance defence mechanism. The physiological function of the mucociliary apparatus was not negatively affected in any of the two epithelial models. Airway mucus crosslinked by mucomodulators is better cleared from an intact airway and normally functioning respiratory system, either due to enhanced interaction with cilia or airflow-dependent mechanisms. Data obtained in this study allow us to assure that we have complied with the fundamental requirement criteria established in the initial phase of developing the concept of mucomodulation: Can we modulate the physical characteristics of the respiratory secretions to reduce aerosolization without affecting normal mucociliary clearance function, or even better improving it?
Zayas
Gustavo
G
University of Alberta Pulmonary Research Group, Edmonton, Canada. g.zayas@ualberta.ca
Valle
Juan C
JC
Alonso
Mauricio
M
Alfaro
Henry
H
Vega
Daniel
D
Bonilla
Gloria
G
Reyes
Miguel
M
King
Malcolm
M
D000336:Aerosols; D000818:Animals; D001001:Anura; D002923:Cilia; D003371:Cough; D004285:Dogs; D005260:Female; D006920:Hygiene; D008297:Male; D009079:Mucociliary Clearance / Q000502:physiology*; D009093:Mucus; D010159:Palate; D020545:Respiratory Mucosa / Q000737:chemistry* / Q000502:physiology*; D012140:Respiratory Tract Diseases / Q000517:prevention & control*; D014132:Trachea / Q000502:physiology; D014783:Viscosity
D000336:Aerosols
Adv Drug Deliv Rev. 2002 Dec 5;54(11):1475-90
12458156
Respir Res. 2004;5:9
15357881
Eur J Respir Dis Suppl. 1987;153:130-5
3322857
Am Rev Respir Dis. 1988 Mar;137(3):707-10
3345048
BMC Pulm Med. 2005;5:11
16138926
Biorheology. 1989;26(4):737-45
2611367
Am Rev Respir Dis. 1990 Apr;141(4 Pt 1):1040-3
2327638
J Appl Physiol (1985). 1990 Aug;69(2):424-9
2228850
Can Respir J. 1999 May-Jun;6(3):246-52
10393286
Biorheology. 1987;24(6):589-97
3502760