Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 749

In healthy non-smoking adults, tracheal mucociliary clearance rate can be
assessed by a radioisotope technique (70-85 m/s; i.e., from 4.3 ± 1.1 mm/mn

[ 1518 ]to5.1 ± 2.9 [ 1517 ]). However, mucociliary clearance rates of 100 to

300 m/s have been measured in the human trachea, i.e., nearly an order of

magnitude greater [ 1519 ]. In the latter study, intersubject variations of mucus
transport rate is not correlated to variations in ciliary beat frequency of nasal cells
of examined subjects (12.1 ± 1.7 Hz) measured in vitro.

12.2.1 Factors of the Mucociliary Clearance

Four main factors determine efficiency of basic mucociliary clearance: (1) number
of cilia that synchronously beat; (2) cilium beating amplitude and frequency (i.e.,
velocity of cilium tips); (3) thickness of serous fluid and mucus layers produced
by surface goblet cells and submucosal glands; and (4) composition and rheology
of serous fluid and mucus (i.e., ion transport and associated epithelial water flux
as well as macromolecule content and its degree of entanglement and density of
protein crosslinking).
Efficient mucociliary transport requires appropriate mucus composition for
optimal flow, i.e., appropriate epithelial water and ion transport and mucin secretion,
adequate numbers of functioning ciliated cells and their coordinated motion for
mucus propulsion, suitable airway surface liquid depth, as well as respiratory
epithelium integrity over long distances. Efficient transfer of momentum between
cilia and mucus requires that cilia contact mucus during forward stroke, but
minimally interact with it during return. When epithelial lining fluid is either too
deep or too shallow, the mucociliary clearance rate decreases. Moreover, ciliary
activity is adjusted in response to varying environmental conditions (Sect. 12.6.2 ).
Hyaluronan, or hyaluronic acid, a glycosaminoglycan lubricant at the airway
epithelium surface, enhances the transport of airway mucus by cilia and by cough
as well as protects the airway epithelial barrier; the lower the hyaluronan molecular
weight, the stronger the effect [ 1520 ]. Low-molecular-weight hyaluronan (40 kDa)
increases the expression of tight junction proteins such as ZO1 as well as the gap
junction function.

12.2.2 Cough Clearance

Air flow-mucus interaction becomes important in clearing respiratory mucus as
a lung disease develops. Moreover, various lung diseases are characterized by
mucus hypersecretion and impaired airway clearance. Hence, excess mucus must
be eliminated by coughing that propels mucus layer parts.
Efficiency of cough clearance depends on mucus rheology and surface properties
at both air-mucus and epithelial lining fluid-mucus interfaces. Strong mucus