Morphology of mucus films in lung airways: secretion and ciliary evacuation

TL;DR

Airway mucus forms a protective film that is transported by wall-attached cilia, but the film is prone to Rayleigh-Plateau instability that tends to create humps and plugs. The authors implement a reduced-order axisymmetric thin-film model (WRIBL) with open axial boundaries, a wall velocity representing ciliary transport, and localized secretion, and analyze stability and dynamics via linear and spatio-temporal methods plus simulations. They identify three morphologies as mucus input increases: flat films, traveling unduloids, and mucus plugs; open boundaries enable the flat-film state by convecting disturbances, while secretion lowers the threshold for plugging and shifts plug formation toward the secretion zone. The results clarify how baseline secretion maintains a protective film and how hypersecretion promotes plugs, with implications for mucociliary clearance and airway diseases; they also point to future work incorporating non-Newtonian mucus rheology and two-way coupling between mucus and cilia.

Abstract

Lung airways are lined by a film of mucus which protects the epithelium from inhaled particles. To maintain a uniform coating, the mucus that is secreted into airways must be distributed into a film by wall-attached cilia, which constantly convey mucus along the airway. However, the film's natural tendency is to accumulate into humps and plugs, due to the Rayleigh-Plateau instability. To understand the behaviour of the film amidst these competing factors, we perform simulations of an idealized tubular airway using a reduced-order thin-film model. The axial boundaries are nonperiodic, allowing for cilia-driven inflow and outflow; a tangential velocity along the tubular wall models ciliary transport, while a localized source at the wall accounts for secretion. On increasing the mucus input rate, we find three distinct film morphologies: (i) uniform flat films; (ii) nonuniform films that are composed of travelling unduloid-shaped humps, separated by mucus-depleted zones; and (iii) films that form an occluding plug. The flat-film regime, absent in closed periodic domains, emerges as a consequence of the convective nature of the Rayleigh-Plateau instability in the presence of ciliary transport. Higher secretion rates increase the mean film-thickness and induce a convective-to-absolute transition, which manifests in the appearance of travelling humps. In the plug-forming regime, capillary forces dominate and drive the incoming mucus into a single hump, which resists ciliary translation and remains near the mucus source. Our results show how low-level baseline secretion sustains a protective, uniform mucus film, and how hypersecretion -- stimulated, for example, by inhaled allergens -- produces mucus plugs.

Figures (4)

• Figure 1: Illustration of a mucus-lined ciliated airway with a mucus-secretion site (top half) and schematic of the corresponding model (bottom half). The airway, of length $L$, has open boundaries in the axial direction through which mucus flows in and out of the domain.
• Figure 2: (a) Map demarcating the dynamical regimes encountered on varying the mucus input flow rate $I_c$, which in turn sets the thickness $1-d_0$ of the flat base-state (see the top and bottom horizontal axes of panel (a)). The vertical axis shows the minimum position attained by the interface, $d_{min}$. Illustrations of the film's evolution in the three regimes are presented in panels (b-c). Here $u_c U = 60$ μ m.s^-1; analogous results for $u_c U = 40$ μ m.s^-1 are presented in the https://bighome.iitb.ac.in/index.php/s/yeijAoz47zg7yZk.
• Figure 3: (a-b) Contours of $\omega_i$ in the $k_r$-$k_i$ plane for convectively and absolutely unstable base films; the red "$+$" marker locates the saddle pinch point and the dotted lines correspond to the $\omega_i = 0$ contour. A Jupyter notebook that derives \ref{['dispersion']} and plots panel (a) is available at https://cocalc.com/share/public_paths/af07785cc665fccfb4c2939f0996ad2001ecb4b1. (c) The convective-absolute boundary (pink-dashed) along with numerically-determined transition points (black circles) between the flat-film and travelling-hump regimes.
• Figure 4: (a) Regime map demarcating the different behaviours of the film downstream of the secretion zone (located at $z=z_s=19.7$); here, the mucus secretion rate $I_s$ is varied. Illustrations of the film's evolution in the three regimes are presented in panels (b-d). Here $u_c U = 60$ μ m.s^-1; analogous results for $u_c U = 40$ μ m.s^-1 are presented in the https://bighome.iitb.ac.in/index.php/s/yeijAoz47zg7yZk.