A new paradigm in respiratory hygiene: increasing the cohesivity of airway secretions to improve cough interaction and reduce aerosol dispersion

Abstract

Background: Infectious respiratory diseases are transmitted to non-infected subjects when an infected person expels pathogenic microorganisms to the surrounding environment when coughing or sneezing. When the airway mucus layer interacts with high-speed airflow, droplets are expelled as aerosol; their concentration and size distribution may each play an important role in disease transmission. Our goal is to reduce the aerosolizability of respiratory secretions while interfering only minimally with normal mucus clearance using agents capable of increasing crosslinking in the mucin glycoprotein network.

Methods: We exposed mucus simulants (MS) to airflow in a simulated cough machine (SCM). The MS ranged from non-viscous, non-elastic substances (water) to MS of varying degrees of viscosity and elasticity. Mucociliary clearance of the MS was assessed on the frog palate, elasticity in the Filancemeter and the aerosol pattern in a "bulls-eye" target. The sample loaded was weighed before and after each cough maneuver. We tested two mucomodulators: sodium tetraborate (XL"B") and calcium chloride (XL "C").

Results: Mucociliary transport was close to normal speed in viscoelastic samples compared to non-elastic, non-viscous or viscous-only samples. Spinnability ranged from 2.5 +/- 0.6 to 50.9 +/- 6.9 cm, and the amount of MS expelled from the SCM increased from 47 % to 96 % adding 1.5 microL to 150 microL of XL "B". Concurrently, particles were inversely reduced to almost disappear from the aerosolization pattern.

Conclusion: The aerosolizability of MS was modified by increasing its cohesivity, thereby reducing the number of particles expelled from the SCM while interfering minimally with its clearance on the frog palate. An unexpected finding is that MS crosslinking increased "expectoration".

Figure 1

Schematic diagram of the macromolecules of mucus with the different types of crosslinks. Sodium tetraborate would contribute to crosslink formation involving accessible galactose moieties in the oligosaccharide side-chains. Calcium chloride would add crosslinking through divalent ionic interactions.

Figure 2

Effect of the crosslinking agent XL "B" (sodium tetraborate) on spinnability in artificial mucus. * p < 0.05 with respect to 150 μL; ** p < 0.01 with respect to 150 μL.

Figure 3

Cough clearance ("expectoration") of sodium tetraborate (XL :B") crosslinked mucous gel simulants, i.e. the percentage of initial load clearing the mouth of the artificial trachea during the cough maneuver. ** p < 0.01 with respect to 150 μL.

Figure 4

Aerosolization and dispersion pattern effects for sodium tetraborate crosslinked mucous gel simulants. Aerosol pattern at 40 cm. following a standardized cough maneuver. Both the amount of aerosol striking the target and the amount of fine aerosol decreased progressively with added crosslinking agent.

Figure 5

Effect of the crosslinking agent calcium chloride (XL "C") on the physical changes of the fresh frog mucus. SE micrograph showing the "clumping" effect of calcium chloride applied topically to the frog palate. The ciliated surface of the palate is seen below the mucus and does not appear different from control views.

Figure 6

Effect of different concentrations of sodium tetraborate (XL "B'') on MTV of frog mucus. * p < 0.05 with respect to the other concentrations.