Abstract

Human pulmonary epithelial cells are protected by two layers of fluid—the outer watery periciliary liquid layer (PCL) and the uppermost non-Newtonian mucus layer (ML). Aerosols and inhaled toxic particles are trapped by the ML which must then be removed swiftly to avoid adverse health implications. Epithelial cells are covered with cilia that beat rapidly within the PCL. Such ciliary motion drives the mucus transport. Although cilia can penetrate slightly inside the mucus to assist mucus movement, the motion of the underlying PCL layer within the airway surface liquid (ASL) is significant in mucus and pathogens transport. As such, a detailed parametric study of the influence of different abnormal cilia characteristics, such as low beating frequency, short length, abnormal beating pattern, reduced ciliary density, and epithelium patchiness due to missing cilia on the PCL transport, is carried out numerically. Such abnormalities are found in various chronic respiratory diseases. In addition, the shear stress at the epithelium is assessed due to the importance of shear stress on the epithelial function. Using the immersed boundary (IB) method combined with the finite-difference projection method, we found that the PCL, under standard healthy conditions, has net forward motion but that different diseased conditions decrease the forward motion of the PCL, as is expected based on clinical understanding.

Highlights

  • Airway surface liquid (ASL) covers the respiratory epithelia that is mainly comprised of two distinct layers: mucus layer (ML)—a non-homogenous, non-Newtonian, viscoelastic fluid [1]; and periciliary liquid layer (PCL)—treated as a watery lubricating fluid layer with much less viscosity [2]

  • Transport of the ASL is of vital importance to keep the respiratory system clear from inhaled particulate matters deposited on the ML

  • By using a finite-difference fluid solver coupled to an immersed boundary (IB) method, we first examined cilia-driven fluid flows, and thorough parametric studies were performed to better understand the fluid flow characteristics of PCL in humans with ciliary disorders

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Summary

Introduction

Airway surface liquid (ASL) covers the respiratory epithelia that is mainly comprised of two distinct layers: mucus layer (ML)—a non-homogenous, non-Newtonian, viscoelastic fluid [1]; and periciliary liquid layer (PCL)—treated as a watery lubricating (nearly Newtonian) fluid layer with much less viscosity [2]. Transport of the ASL is of vital importance to keep the respiratory system clear from inhaled particulate matters deposited on the ML. Such clearance mechanism is facilitated by periodic ciliary actions, with the ASL being swept forward during the effective stroke and backward during the recovery stroke [3]. There are generally two main reasons for muco-ciliary dysfunction in the respiratory system: airway mucosal diseases (such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), asthma, etc.) and ciliary abnormalities. Mucosal diseases occur in patients as a result of the conversion from healthy to pathologic mucus, where the mucus hydration and its biochemical constituents change by multiple

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