Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 750

elasticity that favors recoil after cough impedes mucus propulsion toward the larynx.
High adhesivity precludes cough clearance. In addition, mucus sheared by strong
expiratory air flow during coughing is prevented from sedimenting, as it rapidly
recovers its rheological features and does not undergo tearing.

12.2.3 Mucociliary Clearance and Infection

The mucociliary clearance is a major defense process of the airway epithelium
against inhaled pathogens and noxious entrapped micro- and nanoparticles that
are removed with the mucus layer from the respiratory tract. As an innate airway
defense mechanism, the mucociliary clearance affects drug delivery to airways.
Drug absorption depends on duration during which drug is retained, i.e., the rate
of mucus transport that is usually slowed down in airway pathologies. Engineered
nanoparticles must be able to cross viscoelastic and adhesive mucus barrier, limit
interactions with mucus constituents, and avoid adhesion and rapid clearance to be
delivered in target cells.
Among normal volunteers exposed to rhinovirus or influenza-B virus, some
remain uninfected, whereas others experience subclinical or symptomatic infection.
Most symptomatic infected volunteers have prolonged nasal clearance, and less than
50% of their epithelium ciliated, but without significant reduction in ciliary beat
frequency [ 1521 ].

12.2.4 Alterations in Mucociliary Clearance

Altered mucus composition causes abnormal mucociliary transport. Dysfunctional
ion channels, such as CFTR and ENaC, that generate depletion of airway surface
liquid produce mucus adhesion that favors formation of mucus plaque and plug,
thereby an attenuated clearance of inhaled pathogens. Defective chloride trans-
port across mucous membranes prevents normal hydration of mucus, leading to
accumulation of highly viscous mucus such as that observed in cystic fibrosis.
Mucus-generated clogging in airways, inflammation, and infection cause structural
changes in lungs and sinuses. Mucus with elevated viscosity reduces air flow and
fails to adequately clear germs.
Loss of water and salt in the airway surface liquid induces collapse of both
the lubricating and mucus layers and mucus adhesion to cell wetted surface. On the
other hand, addition of water and electrolytes to the airway surface liquid swells the
mucus layer, but maintains apposition of both strata.
Ciliary activity that depends on appropriately hydrated airway surface liquid is a
dominant factor that govern mucus clearance. In fact, individuals with mucoviscido-
sis, hence depleted airway surface liquid, quickly develop severe airway infection,
whereas asthma that is associated with mucin hypersecretion is not necessarily
associated with infection.